1 - External Diseases

Editors: Tasman, William; Jaeger, Edward A.

Title: Wills Eye Hospital Atlas of Clinical Ophthalmology , The, 2nd Edition

Copyright 2001 Lippincott Williams & Wilkins

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Chapter 1

External Diseases

Elisabeth J. Cohen

Christopher J. Rapuano

Peter R. Laibson

Recurrent lattice corneal dystrophy in a corneal transplant before (A) and after (B) excimer laser phototherapeutic keratectomy.



Anatomy of the Cornea

The precorneal tear film is generally considered as the most anterior aspect of the cornea and is about 7 m thick. It is firmly adsorbed onto the anterior layer of the corneal epithelium by mucoproteins of the mucoid tear film layer attached to the microvilli of the superficial epithelial cells.

Beneath the precorneal tear film, the corneal epithelium is 50 m thick and is composed of five to eight layers of epithelial cells (Fig. 1.1). The inner layer consists of basal epithelial cells that are responsible for producing the epithelial basement membrane, which maintains adherence of the epithelium to Bowman's layer. Above the basal epithelial layer are several rows of wing cells that are somewhat flattened. Progressively flatter and thinner layers of epithelial cells progress to the outer surface layer, which contains the microvilli. The epithelium constitutes about 10% of the corneal thickness.

Beneath the epithelium is Bowman's layer, which is the most anterior layer of the corneal stroma. It is a uniform collagen layer firmly anchored at the limbus. Bowman's layer does not swell as the stroma does, because Bowman's layer is composed of firmly compacted collagen fibrils.

The stroma, which makes up 90% of the cornea, has three components: collagen fibers, or lamella, surrounded by a ground substance and interspersed with occasional stromal keratocytes. The regular arrangement of the collagen fibrils and its relation to the mucopolysaccharide ground substance provides corneal clarity.

Beneath the stroma is Descemet's membrane, an acellular, strong, elastic membrane that is the basement membrane of the corneal endothelium and is produced by a secretion of the corneal endothelium. It grows throughout life and becomes slightly thicker with advanced age. It is usually 3 m thick at birth and can grow to 30 to 40 m in old age. In certain diseases, such as endothelial and Fuchs' dystrophies, Descemet's membrane is even thicker, and the nonbanded posterior portion can be extremely thick compared with the normal membrane.

Figure 1.1. The anatomy of the cornea. (Ep, epithelium; Bo, Bowman's layer; St, stroma; De, Descemet's membrane; En, endothelium.)

Figure 1.2. A: Specular microscopy of normal corneal endothelium. The endothelial cell count was approximately 3,200 cells/mm2. B: Endothelial specular microscopy revealed endothelial dystrophy with areas of endothelial cell drop-out. Between the areas of endothelial drop-out, the endothelial cell count was relatively normal. This patient did not have stromal or epithelial edema.

The endothelium is a single layer of cells responsible for corneal stromal hydration. The endothelial cells seldom divide, and with aging, inflammation, trauma, or endothelial dystrophy, the endothelial cell count diminishes. The cell count may be 5,000 to 6,000 mm2 at birth but 1,000 or less later in life (Fig. 1.2A,B). As the endothelial cells die out and disappear, the adjacent endothelial cells thin and spread out to take their place, diminishing the endothelial cell count.


Infectious Blepharitis

Blepharitis is a common condition of the eyelids causing chronic ocular irritation and foreign body sensation. It is associated with thickening of the eyelids, telangiectatic vessels along the lid margins, and plugging of the meibomian glands


(Fig. 1.3A,B). There is usually crusting along the eyelashes and sometimes misdirection and loss of eyelashes. Staphylococcus bacteria are the most common offending organisms. In many patients, blepharitis is associated with rosacea, manifested by telangiectatic vessels on the facial skin, and with rhinophyma in more advanced cases (Fig. 1.4).

Figure 1.3. A: Blepharitis is associated with crusting of the eyelashes, thickening of the eyelids, telangiectatic vessels along the lid margins, and plugging of the meibomian glands. B: The meibomian glands become plugged in posterior blepharitis with or without rosacea.

Good lid hygiene with mechanical scrubbing of the lid margins, warm compresses, and antibiotic ointment at bedtime using bacitracin or erythromycin is the standard treatment for blepharitis. Patients whose condition is unresponsive, those who have rosacea, or those who have corneal complications such as margin infiltrates benefit from the use of systemic tetracycline (250 mg, orally four times each day for 1 week, then twice daily) or doxycycline (100 mg, orally twice daily for 1 week, then once daily). Systemic erythromycin is an alternative to systemic doxycycline for patients who are unable to tolerate doxycycline and for children who cannot take doxycycline because it stains developing teeth.

Stye, Hordeolum, and Chalazion

Patients with blepharitis are prone to hordeola, styes, and chalazia, which are inflammations of the eyelid glands. A stye, or external hordeolum, is an abscess of a gland of Zeis at the lid margin (Fig. 1.5A). An internal hordeolum is an infection within the meibomian gland deeper in the tarsus (Fig. 1.5B). Both are acute, painful lid nodules, tender to the touch, which produce lid swelling and redness and which may point as the abscess localizes. Chalazia are subacute, nontender nodules associated with granuloma formation in response to meibomian gland lipid extravasated within the tarsus (Fig. 1.5C).

Hordeola typically respond to warm compresses within several days. Occasionally, incision and drainage are necessary. Chalazia usually respond to 15-minute warm compresses four times each day for 2 weeks, but they may require steroid injection or surgical excision. The underlying lid disease in both cases should be treated with warm compresses and antibiotic ointment. Recurrent chalazia can be prevented in many cases by systemic tetracycline. Recurrent chalazia removed surgically should be sent for pathologic analysis. Sebaceous cell carcinoma can masquerade as recurrent chalazia.

Seborrheic Blepharitis

Seborrheic blepharitis refers to crusting of the eyelids associated with seborrheic dermatitis of the eyebrows and scalp


without meibomian gland inflammation or staphylococcal infection. Crusting of the lashes can occur without inflammation of the lid margin posterior to the lashes (Fig. 1.6).

Figure 1.4. Blepharitis may be associated with rosacea that is manifested by telangiectatic vessels on the skin and, as in the advanced case shown here, with rhinophyma.

Figure 1.5. A: Stye of the upper eyelid. B: Hordeolum pointing on the inner aspect of the lid and at the meibomian gland opening at the lid margin. C: A chalazion is a nontender nodule of the lid consisting of a granulomatous reaction to meibomian lipid.

Treatment consists of warm compresses, lid scrubs, and shampoo for the treatment of seborrhea.

Atopic Blepharitis

Atopic blepharitis occurs in patients who have atopic dermatitis involving the eyelids. In atopic blepharitis, lichenification of the eyelids often is complicated by cracking of the eyelids nasally and temporally (Fig. 1.7).

Lubrication of the eyelids with ophthalmic ointments may be sufficient in mild cases, but patients often require application of steroid ophthalmic ointment to the eyelids once or twice daily to control symptoms. They must be closely monitored for complications of steroids, including intraocular pressure elevation, because the steroids are absorbed into the eye. Topical antihistamines and mast cell stabilizers have variable efficacy. In severe cases, topical cyclosporine can be effective in decreasing or eliminating the need for topical corticosteroids. Optimization of systemic treatment of atopy is indicated and may reduce or eliminate the need for application of steroids to the eyelids. Atopic patients are prone to colonization with staphylococci and streptococci, and they may benefit from the application of bacitracin or erythromycin ointment at bedtime.

Contact Dermatitis

Contact dermatitis is a type IV delayed hypersensitivity reaction to topical ophthalmic medication. A periocular


eczematoid reaction develops after several days or longer of exposure to the offending medication (Fig. 1.8). Neomycin and atropine are common causes, but any ophthalmic medication can be involved.

Figure 1.6. Seborrheic blepharitis is associated with crusting of the eyelids without meibomian gland inflammation and with seborrheic dermatitis of the eyebrows and scalp.

Figure 1.7. In atopic blepharitis, there is an eczematoid reaction of the eyelids.

Discontinuing the topical medication is sufficient treatment in most cases. In severe cases, topical steroid ointment can be used to speed recovery. Patients should be informed that they are allergic to the medication causing the reaction. If the patient is on multiple medications, the physician may discontinue them all or only the most likely one, depending on the severity of the reaction.

Molluscum Contagiosum

Molluscum contagiosum is a DNA pox virus infection that causes single or multiple umbilicated lid lesions that may cause a toxic follicular conjunctivitis (Fig. 1.9A,B). In immunocompromised hosts, such as patients with acquired immunodeficiency syndrome, lesions may be greater in number, but they are not associated with conjunctivitis.

Figure 1.8. Contact dermatitis is a delayed hypersensitivity reaction to topical ophthalmic medication causing a periocular eczematoid reaction.

Figure 1.9. A: Molluscum contagiosum is associated with single or multiple umbilicated lid lesions. B: At higher magnification, the depressed center of these lesions is more apparent.

Treatment requires excision of the lesions in most cases. Observation of the lesions may be sufficient for patients without conjunctivitis.

Blepharitis Caused by Lice Infestation

Infestation of the eyelids by pubic lice (Phthiriasis pubis, crabs) is a cause of chronic blepharoconjunctivitis. It is a sexually transmitted disease.

Patients with lice infestation experience irritation of the eyelids and mild crusting. Slit lamp examination reveals globular nits (i.e., eggs) attached to the eyelash shaft. Fully developed adult lice are seen among the eyelashes, often partially embedded in the skin (Fig. 1.10). Movement of the lice's appendages can be seen. Characteristically, blood-tinged debris is present along the base of the lashes.

The lice and eggs should be removed mechanically, using fine forceps if feasible. Trimming the lashes is another treatment option. Any petroleum-based jelly applied to the eyelids three times daily for 10 days smothers the lice. Bacitracin or erythromycin ointment can be used for this purpose. An application of physostigmine (Eserine) ointment paralyzes the adult lice but does not affect the nits; therefore a second application may be necessary in 7 days.


The accompanying pupillary miosis produced by physostigmine ointment is uncomfortable, and this treatment is rarely used anymore. Nonocular, moist, hair-bearing areas should be treated with Kwell shampoo. Clothes and bedding should be thoroughly washed.

Figure 1.10. Eyelid infestation with Phthiriasis pubis. An adult crab louse can be seen at the lash line with numerous nits (i.e., eggs) attached firmly to the eyelash shafts.


Viral Conjunctivitis

Acute follicular conjunctivitis is most commonly caused by adenoviral infection and is referred to as epidemic keratoconjunctivitis (EKC). EKC is often associated with an upper respiratory tract infection and preauricular adenopathy. It spreads from one eye to the other, and the eye infected second is less involved. Less common causes of acute follicular conjunctivitis include herpes simplex infection and acute hemorrhagic conjunctivitis.

Figure 1.11. A: Viral conjunctivitis is associated with an acute follicular reaction. In follicles, vessels course on the surface from the periphery of the lesions toward the center rather than emerging in the center, as is the case in papillae. B: Acute adenoviral conjunctivitis with subconjunctival hemorrhage and pseudomembrane formation. C: In severe adenoviral conjunctivitis, the patient may have lid ecchymoses in addition to subconjunctival hemorrhages. D: During the second week, subepithelial infiltrates develop in patients with epidemic keratoconjunctivitis. In most cases, the infiltrates gradually resolve over many months.

The onset of adenoviral conjunctivitis is sudden, with diffuse lid swelling and conjunctival redness. The eyes are uncomfortable, produce tears, and have a foreign body sensation. Follicles appear as elevations in the inferior palpebral conjunctiva, with vessels coming from the periphery (Fig. 1.11A). There may be subconjunctival and lid hemorrhages, a discharge, and pseudomembranes in severe cases (Fig. 1.11B, C). Corneal involvement follows a typical pattern, with intraepithelial microcysts developing during the first few days, followed by fluorescein-staining epithelial hyperplasia. Subepithelial infiltrates (Fig. 1.11D) appear during the second week as the ocular injection and infection are resolving. The subepithelial infiltrates gradually get smaller and resolve in most cases over several months.

Viral conjunctivitis is highly contagious, and precautions, including hand washing and disinfection of exposed surfaces, are necessary for the patient and physician to avoid spreading the disease by hand-eye-hand contamination. There is no specific treatment for viral conjunctivitis. Most cases are treated supportively with cool compresses and lubricating drops. In severe cases associated with acute incapacitating discomfort, pseudomembranes, corneal erosions, or significantly reduced vision as a result of subepithelial infiltrates, topical corticosteroids are used, although they may prolong the course of the disease.

Allergic Conjunctivitis

A history of atopy and papillary reaction of the superior tarsus seen when the upper eyelid is everted are common to a variety of forms of allergic conjunctivitis. Itching is the major symptom of ocular allergy. Seasonal (i.e., hay fever) and perennial allergic conjunctivitis are usually associated with rhinitis. The conjunctival injection is mild to moderate.



Velvety papillae are maximal along the superior border of the superior tarsus.

Figure 1.12. A: Vernal keratoconjunctivitis is associated with giant papillae or cobblestones of the superior tarsus and with a ropy, adherent, mucous discharge. B: Trantas dots are infiltrates at the limbus that are composed predominantly of eosinophils. C: In severe vernal keratoconjunctivitis, superficial sterile shield ulcers require topical steroid treatment. D: Giant papillary conjunctivitis is characterized by papillae of the superior tarsus, which are thought to be caused by an allergic reaction to the coating on foreign bodies such as contact lenses or exposed sutures.

In vernal keratoconjunctivitis, giant papillae or cobblestones cover the entire superior tarsus, and there is often a ropy, adherent mucous discharge (Fig. 1.12A). Some patients have limbal follicles or Horner-Trantas dots, which are composed of eosinophils (Fig. 1.12B). In severe forms of vernal keratoconjunctivitis, shield ulcers of the cornea develop, usually superiorly (Fig. 1.12C).

Giant papillary conjunctivitis appears similar to a mild form of vernal conjunctivitis (Fig. 1.12D). It is seen in patients with contact lenses, exposed sutures, or ocular prostheses.

Atopic keratoconjunctivitis is associated with atopic blepharitis and papillary conjunctivitis. In severe cases, it can be complicated by corneal neovascularization and scarring and by anterior cortical cataracts (Fig. 1.13).

Treatment varies according to the type of allergic conjunctivitis. Avoidance of the allergen, when possible, and systemic control of allergies are helpful. Cool compresses and topical lubrication may suffice in mild cases. Topical antihistamines (e.g., levocabastine) and nonsteroidal antiinflammatory agents (e.g., ketorolac) are useful in treating acute seasonal conjunctivitis. Topical mast cell stabilizers (e.g., lodoxamide, cromolyn, etc.) are indicated for vernal conjunctivitis and are useful in treating chronic allergic conditions, including giant papillary and atopic conjunctivitis. Daily or frequent lens replacement and improved lens cleaning, after a period of discontinuing lens wear in more severe cases, are also important in the treatment of lens-related giant papillary conjunctivitis. Topical corticosteroids are necessary for the treatment of shield ulcers and severe flare-ups of vernal and atopic conjunctivitis, but they should be avoided if possible in other types of ocular allergies.

Figure 1.13. In severe atopic keratoconjunctivitis, corneal scarring, neovascularization, and melting can develop.

Bacterial Conjunctivitis

Bacterial conjunctivitis is characterized by conjunctival injection, papillary reaction, and purulent or mucopurulent discharge (Fig. 1.14). It is caused by a wide variety of microorganisms and may be acute, hyperacute, or chronic.

The patient with acute conjunctivitis notices a sudden onset of redness of the eye that is accompanied by a discharge and sticking together of the eyelids in the morning. Tearing and irritation may be experienced, but significant pain is rare. The condition is usually unilateral but may be bilateral. There is injection of the epibulbar and palpebral conjunctiva, and a papillary reaction is found in the inferior palpebral conjunctiva. The discharge may vary from frank pus to a scant mucopurulent excretion. The lashes are frequently crusted. The most common bacteria associated with acute conjunctivitis are Staphylococcus, Streptococcus, and Haemophilus influenzae.

Hyperacute conjunctivitis is usually bilateral and is characterized by the sudden onset of conjunctival redness and chemosis, lid swelling, and copious purulent discharge (Fig. 1.15A, B). Pain, tenderness to touch, and preauricular lymphadenopathy are common. The most common pathogens causing hyperacute conjunctivitis are gonococcus and meningococcus, but other organisms, such as Staphylococcus aureus and Streptococcus, may produce this picture. In untreated gonococcal infection, corneal involvement occurs frequently. In gonococcal conjunctivitis, corneal ulcers typically begin at the superior limbus (Fig. 1.16A). Corneal ulcers rapidly progress if inadequately treated, and they may perforate within 1 to 2 days (Fig. 1.16B). Hyperacute conjunctivitis may be associated with pseudomembrane formation and subsequent conjunctival scarring or symblepharon.

Chronic conjunctivitis is a condition with low-grade symptoms and findings that can be annoyingly persistent. The symptoms are nonspecific and include foreign body sensation, intermittent redness, and mild mattering of the lids. Clinical signs may be minimal, with mild conjunctival


injection and discharge. Blepharitis, styes, and chalazia often accompany chronic conjunctivitis.

Figure 1.14. Acute bacterial conjunctivitis with mild lid swelling, conjunctival injection, and discharge along the lid margin.

Figure 1.15. A: Hyperacute gonococcal conjunctivitis, with copious mucopurulent discharge and lid swelling. B: Hyperacute conjunctivitis caused by meningococcal infection with mucopurulent discharge.

Acute bacterial conjunctivitis is treated with broad-spectrum antibiotic drops, such as trimethoprim-polymyxin (Polytrim), the fluoroquinolones (i.e., Ocuflox, Ciloxan), or an aminoglycoside (e.g., Tobrex, gentamicin). Supplementary ointments, such as bacitracin or erythromycin at bedtime, may be helpful, and ointments are more effective in children. Neomycin with polymyxin B and sodium sulfacetamide preparations have been used for many years, but allergic reactions to these agents are common. In routine cases, cultures are not obtained because most cases are self-limited or respond to treatment. When unusual circumstances, persistent disease, or corneal involvement is present, culture and sensitivity studies are indicated. Underlying dacryocystitis can cause refractory mucopurulent conjunctivitis requiring systemic antibiotics.

In hyperacute conjunctivitis, smears and cultures are necessary, particularly if gonococcal or meningococcal infection is suspected (Fig. 1.17). The treatment of gonococcal conjunctivitis is a single injection of ceftriaxone (1 g) if the cornea is not involved or admission for a 5-day course of intravenous ceftriaxone if the cornea is involved. Topical therapy is ineffective, but bacitracin or ciprofloxacin can be used to supplement systemic therapy. Patients should also be treated with systemic tetracycline for Chlamydia infection and evaluated for other sexually transmitted diseases, including syphilis and human immunodeficiency virus infection.

Figure 1.16. A: In gonococcal conjunctivitis, corneal ulcers begin as infiltrates in the periphery, usually superiorly. B: The rapidly progressing corneal ulcers caused by gonococcal infection can thin and perforate within several days.

Chronic Follicular Conjunctivitis

Chronic follicular conjunctivitis can be caused by Chlamydia infection, trachoma in endemic regions of the world, and drug reactions to epinephrine, antivirals, and a variety of ophthalmic medications.

Follicles occur more frequently in the inferior fornix than in the superior tarsus (Fig. 1.18A,B). In Chlamydia infection, peripheral subepithelial infiltrates may be present (Fig. 1.19A), and if the diagnosis is delayed, superior pannus can develop (Fig. 1.19B). Corneal neovascularization is less common



than in trachoma. In the infected newborn as opposed to the adult, there is more purulent discharge, and follicles are absent.

Figure 1.17. Gram stain of a conjunctival smear from a patient with gonococcal conjunctivitis. Figure 1.15A reveals many polymorphonuclear cells and intracellular gram-negative diplococci.

Figure 1.18. A: In chronic follicular conjunctivitis, follicles occur most frequently in the inferior palpebral conjunctiva. B: Occasionally, a follicular reaction develops on the superior tarsus in patients with chronic follicular conjunctivitis caused by Chlamydia infection.

Figure 1.19. A: In cases of Chlamydia infection, peripheral subepithelial infiltrates develop several weeks after initial infection. B: Occasionally, severe chlamydial conjunctivitis causes corneal pannus formation.

Figure 1.20. A: In trachoma, a mixed papillary follicular reaction of the superior tarsus is followed by conjunctival scarring. B: Linear conjunctival scars parallel to the lid margin due to trachoma are called Arlt's lines. C: Herbert's pits are depressed limbal scars. (Courtesy of the Wills collection.) D: Trachoma can result in corneal scarring and neovascularization.

In trachoma, there is a mixed follicular papillary reaction, predominantly of the superior tarsus, followed by conjunctival scarring, dry eyes, and trichiasis due to cicatricial entropion (Fig. 1.20A-D). Limbal inflammation is followed by the formation of depressed scars called Herbert's pits.

Chlamydia infection is diagnosed by immunofluorescence tests, tissue cultures of corneal scrapings, or both. Polymerase chain reaction testing is available. Chlamydia conjunctivitis in adults is treated with systemic doxycycline or tetracycline for 3 weeks. Erythromycin (250 mg four times daily) can be used as an alternative systemic medication if the patient is allergic to doxycycline or tetracycline or is less than age 8. A single dose of 1 g azithromycin is also effective. In newborns, inclusion conjunctivitis requires systemic erythromycin treatment of the infant and the parents. Trachoma is treated with topical or systemic tetracycline or erythromycin or systemic azithromycin. Eradication of the disease is difficult in endemic areas with poor hygiene because of reinfection, but periodic systemic azithromycin has the potential to eradicate this leading cause of preventable blindness affecting over 100 million people in the Middle East, Africa, and Southeast Asia.

Herpes Simplex Keratitis

Acute Dendritic Herpes Simplex Keratitis

Acute dendritic herpes simplex keratitis is characterized by the sudden onset of superficial corneal ulceration in the form of a dendrite after invasion of the epithelium by the herpes simplex virus (HSV). A dendrite is a branching epithelial ulceration with swollen, raised edges and terminal bulbs caused by active infection of the corneal epithelium with HSV type I (Fig. 1.21A). Primary infections with HSV are usually inapparent, and the virus becomes latent in the trigeminal ganglion. The precipitating factors leading to virus reactivation include fever, ultraviolet exposure, trauma, and stress. The use of topical or systemic corticosteroids is associated with the worsening of dendritic keratitis.

Figure 1.21. A: The hallmark of herpes simplex keratitis is the dendrite, a branching, epithelial ulceration with swollen, raised edges and terminal bulbs. B: In primary herpes simplex virus infections, multiple small dendrites may develop.


Patients notice pain, tearing, foreign body sensation, redness, and sensitivity to light. These symptoms may be mistaken for acute conjunctivitis, and it is important to keep HSV keratitis in the differential diagnosis of a red eye and acute follicular conjunctivitis. Fluorescein staining reveals the typical tree-branching appearance. Occasionally, multiple, small dendrites may be present (Fig. 1.21B). Ghost dendrites, which may follow dendrites, are dendritiform opacities in the superficial stroma (Fig. 1.22A). Dendrites recurring after penetrating keratoplasties for severe corneal scarring as a result of HSV begin in the periphery and may extend into the graft (Fig. 1.22B).

Acute HSV dendritic keratitis is treated with topical antiviral medication using trifluridine drops eight times each day or vidarabine ointment five times each day for 10 to 14 days. Topical steroids are contraindicated.

Figure 1.22. A: Ghost dendrites sometimes develop after herpes simplex dendrites. The ghost dendrites are superficial corneal opacities with the same shape as the original dendrite. They usually fade gradually without additional therapy but may leave superficial scarring. B: When dendrites develop after corneal transplantation for herpes simplex keratitis, they usually develop in the periphery and then extend onto the donor cornea.

Other Manifestations of Ocular Herpes Simplex Virus Infection

Other manifestations of ocular HSV infections include lid blisters, follicular conjunctivitis, conjunctival dendrites, and geographic ulcers. The grouped vesicular lid eruption is extensive in primary infection (Fig. 1.23A). Healing occurs without scarring. Lid margin HSV ulcers (Fig. 1.23B) can be associated with infection of the adjacent corneal and conjunctival epithelium (Fig. 1.23C). Follicular conjunctivitis frequently accompanies primary HSV infection, but it can also be a manifestation of recurrent infection. Dendrites can involve the corneal and conjunctival epithelium. Geographic ulcers are large dendrites with similar epithelial borders but larger central epithelial defects (Fig. 1.24A). Rose bengal vividly stains the virus-infected epithelium



along the border of geographic ulcers (Fig. 1.24B). HSV is also a cause of geographic conjunctival ulcers (Fig. 1.24C).

Figure 1.23. A: In overt primary herpes simplex virus infection, there is a vesicular lid rash that usually does not scar. B: Recurrent herpes simplex disease may produce more limited ulcerative blepharitis. C: When the lid margin is involved, there may be infection of the adjacent conjunctiva and cornea.

Figure 1.24. A: Geographic ulcers are large, dendritic infections of the corneal epithelium. They stain with fluorescein. B: Geographic ulcers and dendrites stain with rose bengal, with the greatest staining occurring along the edge of the ulcer where there is active viral infection. C: Herpes simplex virus infections can also cause conjunctival geographic ulcers.

HSV blepharitis does not require treatment if the lesions are away from the lid margin. If the lid margin is involved, topical antivirals should be used in the eye prophylactically five times each day for 7 days. Follicular conjunctivitis in a patient with a history of recurrent HSV keratitis in the involved eye should also be treated with topical antivirals five times each day. Geographic ulcers are treated with topical trifluridine eight times each day. Prolonged use of antivirals results in toxicity manifested initially by superficial punctate keratitis in a whorl pattern. Treatment is discontinuation of the toxic antiviral medication and the use of preservative-free lubricating drops. Systemic acyclovir alone is effective in the treatment of dendritic keratitis but is not indicated unless standard topical antiviral therapy is unsuccessful. Systemic acyclovir is used in adults with overt primary infections, although this is not an approved use of the drug.

Trophic Epithelial Defects

Noninfectious trophic epithelial defects occur in patients with a history of recurrent HSV keratitis. The trophic defects are epithelial erosions with smooth, rolled edges (Fig. 1.25A). They are presumed to be associated with decreased corneal sensitivity caused by recurrent HSV keratitis. They may be complicated by corneal melting and perforation (Fig. 1.25B) and with microbial superinfection (Fig. 1.25C).

Figure 1.25. A: Persistent trophic epithelial defects have rounded borders. B: Trophic defects can be complicated by corneal thinning, melting, and perforation, (C) and by microbial superinfection. Cultures grew Staphylococcus aureus in this case.

Trophic defects are treated with lubrication, antibiotic ointment, discontinuation of toxic antivirals, and sometimes with patching. A partial temporary tarsorrhaphy is very helpful in promoting epithelial healing when lubrication is insufficient. Progressive melting and small perforations are managed with tissue adhesive and a bandage lens, but an emergency patch graft or penetrating keratoplasty may be necessary for larger perforations.

Stromal Keratitis

Nonnecrotizing Stromal Keratitis

HSV stromal keratitis is divided into nonnecrotizing and necrotizing diseases. Nonnecrotizing HSV stromal keratitis appears as localized corneal edema (Fig. 1.26A,B). Disciform keratitis is a common form of nonnecrotizing HSV stromal keratitis associated with a round area of full-thickness corneal edema that is often accompanied by localized granulomatous keratic precipitates.

The HEDS study showed that topical corticosteroids accompanied by antiviral prophylaxis are safe and effective treatment for nonnecrotizing HSV stromal keratitis, shortening the time until resolution. Topical steroids are often begun with prednisolone (1%, four times daily) and prophylactic


topical antivirals three or four times daily. It is necessary to taper topical steroids slowly, often using 0.125% prednisolone from four times daily to once weekly.

Figure 1.26. A: Disciform keratitis is a form of nonnecrotizing herpes simplex virus (HSV) stromal keratitis associated with a round area of full-thickness corneal edema and localized granulomatous keratic precipitates. B: Nonnecrotizing HSV stromal keratitis is associated with localized corneal edema, which may not have a disciform shape.

The HEDS treatment studies showed that systemic acyclovir is not effective in the treatment of stromal HSV keratitis. The HEDS prevention studies showed that systemic acyclovir 400 mg po bid is effective in significantly reducing recurrences and is most beneficial in patients with a history of stromal keratitis, as they are prone to recurrent stromal keratitis, which results in scarring and loss of vision.

Necrotizing Stromal Keratitis

Necrotizing HSV stromal keratitis, in the past called viral interstitial keratitis, has areas of white stromal infiltrates in addition to corneal edema (Fig. 1.27A,B). Corneal neovascularization is also frequently present. When patients with recurrent HSV keratitis develop staining infiltrates, it is important to rule out microbial superinfection with bacteria or unusual organisms by performing smears and cultures.

Figure 1.27. A,B: Necrotizing herpes simplex virus stromal keratitis is characterized by white stromal infiltrates in addition to corneal edema, usually with neovascularization.

Necrotizing HSV keratitis is treated like nonnecrotizing stromal keratitis, with topical steroids and prophylactic antivirals as previously discussed. Necrotizing stromal keratitis is uncommon, and there were not enough patients in the HEDS study to determine whether systemic acyclovir has a role in its treatment.


Acute granulomatous uveitis or iridocyclitis is another manifestation of ocular HSV disease. Herpetic stromal keratitis may or may not be active at the time of the uveitis.

The onset of HSV anterior uveitis is acute, with pain, redness, and sensitivity to lights. Granulomatous keratic precipitates and anterior chamber flare and cells are seen. Uveitis can result in localized iris atrophy and an irregular, sometimes dilated pupil (Fig. 1.28A,B). Herpetic uveitis is often associated with increased intraocular pressure, which may be an indicator of active viral replication in the anterior chamber.

Treatment of herpetic uveitis includes topical corticosteroids,


prophylactic topical antivirals, cycloplegia, and topical and systemic glaucoma medications such as blockers or carbonic anhydrase inhibitors as needed to control intraocular pressure. Miotics and Xalatan are avoided. The optic nerve and visual fields should be followed closely.

Figure 1.28. A: Herpes simplex virus (HSV) uveitis can result in localized iris atrophy that is best seen in retroillumination. B: The same patient, seen in broad illumination, has an irregular pupil secondary to HSV uveitis.

The HEDS study of acyclovir treatment for herpetic iridocyclitis was terminated because of a lack of enrollment, but a probable benefit of treatment was observed among patients treated with acyclovir 400 mg five times a day for 10 weeks compared to placebo.

Corneal Scarring

HSV keratitis can lead to extensive corneal scarring. It is second only to trauma as the most common cause of unilateral corneal blindness in the United States.

Corneal scarring is manifested by localized opacification, usually with variable thinning and surface irregularity, resulting in reduced vision (Fig. 1.29). Corneal scarring may be severe enough to require corneal transplantation for visual rehabilitation.

Figure 1.29. Recurrent herpes simplex virus keratitis can result in corneal scarring and reduced vision, necessitating a corneal transplant in some cases.

Herpes Zoster Ophthalmicus

Dermatologic Involvement

The hallmark of herpes zoster ophthalmicus is a vesicular skin eruption resulting in scarring in the distribution of one of the branches of the trigeminal nerve. Of the three divisions of cranial nerve V, the first or ophthalmic division is the most commonly affected. Zoster can sometimes occur without a rash, but the diagnosis is much more difficult.

The organism responsible for herpes zoster is the herpes varicella virus, which also causes chickenpox. After the primary chickenpox infection, the varicella virus persists in a latent state in the trigeminal ganglion or sensory ganglion of the spinal cord. Acute zoster infection may develop later in life after a reactivation of the virus. The patient notices progressive discomfort or neuralgic pain on the affected side in the scalp, forehead, temple area, and behind the eye. The pain may precede the rash by a day or two and initially puzzle the clinician. The rash is vesicular and results in scarring. Skin involvement strictly obeys the midline (Fig. 1.30). The three main branches of the ophthalmic division are the supraorbital, lacrimal, and nasociliary. One or more branches may be involved. Because the globe is innervated by the nasociliary branch, the likelihood of ocular involvement increases to 75% if this branch is affected. This branch also supplies the skin on the bridge and tip of the nose. If this area is not affected, only approximately one third of the eyes become involved.

The patient often develops conjunctival injection and discharge even without intraocular involvement. If the rash involves the eyelid, cicatricial contraction may result in corneal exposure and/or trichiasis.

Patients with acute herpes zoster ophthalmicus are treated with acyclovir (800 mg, five times daily) for 7 to 10 days. Alternative treatment includes famciclovir (500 mg tid) or valacyclovir (1,000 mg tid), but the latter is not used



in immunocompromised hosts. Use of systemic corticosteroids to prevent postherpetic neuralgia is controversial, and they are much less frequently used than in the past. Topical antibiotics and cold compresses are helpful for conjunctivitis. A dermatologist may be consulted for additional topical treatment of the vesicular lesions.

Figure 1.30. The hallmark of herpes zoster is a vesicular skin eruption of the first division of the fifth cranial nerve that strictly obeys the midline and results in scarring.

Figure 1.31. Early in the course of the disease, patients with herpes zoster ophthalmicus have conjunctivitis and punctate keratitis, which may have a dendritic appearance mimicking herpes simplex virus keratitis.

Figure 1.32. A: Classic zoster pseudodendrites are elevated mucous plaques with tapered ends, which have a delayed onset. B: They stain with fluorescein, but are not ulcerated.

Figure 1.33. Disciform keratitis secondary to herpes zoster appears similar to disciform keratitis secondary to herpes simplex.

Figure 1.34. In nummular keratitis, the subepithelial infiltrates are larger and more variable in size than those in adenoviral conjunctivitis.

Ocular Involvement

Acute Lesions

Acutely, patients with herpes zoster ophthalmicus have conjunctivitis and punctate keratitis when the eye is involved. Acute epithelial involvement with punctate keratitis may have a dendriform appearance, mimicking HSV dendritic keratitis (Fig. 1.31). The typical appearance of the rash aids greatly in the diagnosis of herpes zoster, but its appearance may be delayed.

Treatment of conjunctivitis and punctate keratitis is nonspecific, with cool compresses and topical lubrication with or without prophylactic topical antibiotics. Topical antivirals are not effective or indicated. Acyclovir is effective against herpes zoster but is not available as a topical ophthalmic medication in the United States.

Zoster Epithelial Keratitis

Classic zoster pseudodendrites occur later in the course of the disease, after the rash has healed. Zoster pseudodendrites are mucous plaques that are elevated, stain with fluorescein, and have tapered ends (Fig. 1.32A,B). They differ from herpes simplex dendrites, which are epithelial ulcerations with a depressed center and terminal bulbs.

Zoster dendrites are treated with lubrication, using frequent preservative-free drops and ointment. Topical antivirals are contraindicated because they are ineffective and toxic. Topical steroids can be used as needed to treat zoster keratouveitis, which is frequently also present.

Figure 1.35. A: Interstitial keratitis in herpes zoster patients is associated with localized corneal edema, deep corneal neovascularization, and frequently, lipid keratopathy. B: Lipid keratopathy secondary to herpes zoster ophthalmicus. (Courtesy of E. Jaeger, M.D.)

Zoster Stromal Keratitis

Herpes zoster is associated with various forms of stromal keratitis occurring several weeks or more after the acute infection. Zoster can be associated with disciform keratitis that is similar in appearance to herpes simplex disciform keratitis (Fig. 1.33). This condition can follow chickenpox or zoster. Nummular keratitis with scattered subepithelial infiltrates larger and more variable in size than those seen in adenoviral conjunctivitis can develop (Fig. 1.34). Interstitial keratitis with localized corneal edema and deep corneal neovascularization and lipid infiltrates can also occur (Fig. 1.35 A, B).

Stromal keratitis is treated with topical corticosteroids. Mild inflammation may be responsive to low-dose topical steroids. Steroids must be tapered over many months or years. Some patients require long-term, low-dose steroids such as 0.125% prednisolone once each week to prevent flare-ups. Topical antivirals are not used.

Neurotrophic Keratitis

Neurotrophic keratitis with or without corneal melting is a late manifestation of herpes zoster and is related to permanently decreased corneal sensation. Trophic epithelial defects are erosions with smooth borders that are frequently located inferocentrally (Fig. 1.36). Corneal sensation is decreased or absent. Persistent epithelial defects can be complicated by corneal melting, resulting in impending or frank perforation (Fig. 1.37) or by microbial superinfection.

Trophic epithelial defects can be prevented by using preservative-free lubricating drops and ointment in patients with ocular surface irregularities after zoster infection. Trophic defects are treated with bland antibiotic ointments usually without pressure patching. Temporary or permanent lateral tarsorrhaphy can facilitate healing and prevent recurrent surface breakdown. Corneal melts are treated similarly to trophic defects to promote epithelial healing. A tissue



adhesive covered by a bandage lens is used for impending and small perforations (Fig. 1.38A, B). Larger perforations require patch grafts. Topical steroids promote melting in patients with persistent epithelial defects. They should be avoided in patients not already on them and tapered gradually in patients using them.

Figure 1.36. Neurotrophic keratitis in herpes zoster patients is associated with inferocentral corneal erosions with smooth borders.

Figure 1.37. Persistent neurotrophic epithelial defects can be complicated by corneal melting.

Figure 1.38. Small perforation secondary to herpes zoster ophthalmicus before (A) and after (B) application of tissue adhesive and a bandage contact lens.

Figure 1.39. A: Zoster uveitis can result in sector iris atrophy and an irregular pupil. This patient also has an inferior corneal scar following a perforated bacterial ulcer treated with fortified antibiotics and tissue adhesive. B: Zoster uveitis may be severe and associated with hyphemas. This patient also has a neurotrophic epithelial defect.

Zoster Uveitis

Uveitis may accompany keratitis or occur independently. Zoster uveitis is usually associated with granulomatous keratic precipitates and frequently causes increased intraocular pressure. Zoster uveitis can result in sector iris atrophy and an irregular pupil (Fig. 1.39A) more frequently than herpes simplex uveitis. In severe cases, zoster uveitis can be associated with a hyphema (Fig. 1.39B).

Treatment of zoster uveitis consists of cycloplegia and topical steroids on a gradually tapering regimen without topical antivirals. Increased intraocular pressure is treated as needed with aqueous suppressants without miotic agents or Xalatan.

Zoster Episcleritis and Scleritis

Zoster can be associated with episcleritis and scleritis. The clinical features of pain, localized redness, tenderness and swelling of the conjunctiva, episclera, and sclera are similar to those seen in nonzoster cases. Unlike other causes of episcleritis and scleritis, nodular episcleritis can evolve into nodular scleritis in zoster (Fig. 1.40A). Scleritis may be accompanied by localized stromal keratitis (Fig. 1.40B).

Episcleritis is responsive to topical steroids, but scleritis requires systemic nonsteroidal antiinflammatory agents and steroids if the nonsteroidal antiinflammatories are ineffective. Sclerokeratitis is treated with topical steroids for the cornea and systemic medication to control the scleritis.

Figure 1.40. A: Nodular scleritis is characterized by a localized area of scleral and episcleral swelling associated with marked pain. The condition requires systemic treatment with nonsteroidal antiinflammatory agents. Nodular episcleritis has a similar appearance but is responsive to topical steroids. B: In herpes zoster, there can be scleral keratitis with localized scleral inflammation and adjacent corneal edema.

Corneal Ulcers

Sterile Infiltrates

Staphylococcal hypersensitivity keratitis is manifested by sterile marginal infiltrates. Sterile infiltrates are also seen in patients who wear contact lenses.

Staphylococcal marginal infiltrates are usually located superiorly or inferiorly, near where the lid margin rests against the cornea. The infiltrates are frequently concentric to the limbus and have an intervening clear space (Fig. 1.41). The epithelial defect, if present, is usually smaller than the infiltrate. Conjunctival injection is usually localized to the area of the infiltrate. The anterior chamber is quiet.

Sterile infiltrates in contact lens wearers are small (<1 mm), peripheral, often multiple, and nonstaining (Fig. 1.42). They are not associated with pain, corneal edema, or anterior chamber inflammation.

Staphylococcal hypersensitivity infiltrates are responsive to treatment with weak topical steroids. In addition, treatment of the underlying lid disease with warm compresses, antibiotic ointment, and often with systemic tetracycline is indicated to prevent recurrent episodes.

Sterile infiltrates in contact lens wearers are treated by discontinuing use of the lenses. Low-dose antibiotics are frequently prescribed. The cause of the infiltrate may be hypoxia or a reaction to solutions used for disinfection. After the infiltrate resolves, the fit of the lens should be checked, a hydrogen peroxide system of disinfection should be used, and lens use should be limited to daily wear. If the infiltrate is possibly infected, it should be treated as a bacterial ulcer. Steroids are generally to be avoided in lens-related sterile infiltrates


because the problem resolves with lens discontinuation, and the physician does not want to mistreat an early, undiagnosed infected ulcer.

Figure 1.41. Staphylococcal hypersensitivity keratitis is characterized by infiltrates located in the periphery, concentric to the limbus, with an intervening clear space between the infiltrate and the limbus.

Bacterial Ulcers

Corneal ulcers caused by bacteria present as acutely painful infiltrates associated with overlying epithelial defects and an anterior chamber reaction. Frequently, corneal edema surrounds the infiltrate. There may or may not be a mucopurulent discharge, but its presence points to an infectious cause. The most frequent causative organisms are Staphylococcus, Pseudomonas, Streptococcus, and Moraxella, but a wide variety of bacteria may be cultured.

S. aureus corneal ulcers have a more central or radial component than staphylococcal marginal infiltrates (Fig. 1.43). They are associated with more inflammation, including diffuse injection, surrounding corneal edema, and an anterior chamber reaction.

Pseudomonas is the most common cause of ulcers in persons wearing cosmetic soft contact lenses. Ulcers may be severe,


with marked corneal inflammation, edema, and an adherent mucopurulent discharge (Fig. 1.44). Early Pseudomonas infections may not have the characteristic features of more advanced cases (Fig. 1.45). When pseudomonal infection extends onto the sclera, the prognosis for saving the eye is improved by treatment with oral ciprofloxacin (Fig. 1.46A,B).

Figure 1.42. Sterile infiltrates in contact lens wearers are small, peripheral, often multiple, and nonstaining.

Figure 1.43. Infected corneal ulcers are characterized by corneal infiltrates associated with overlying epithelial defects and an anterior chamber reaction. This ulcer caused by Staphylococcus aureus extends toward the center of the cornea and is associated with surrounding corneal edema.

Figure 1.44. Severe Pseudomonas ulcers typically are associated with adherent mucopurulent discharge and can have a ring appearance caused by dense infiltration and edema at the periphery of the ulcer and central corneal thinning.

Figure 1.45. Small Pseudomonas infections may lack the appearance of typical, severe Pseudomonas ulcers. This patient has a radial extension resembling radial keratoneuritis.

Figure 1.46. A: Pseudomonas corneal ulcers that extend to the limbus and onto the sclera are more serious than those that are limited to the cornea. These ulcers require long-term systemic therapy. B: A follow-up photograph of the same patient shows a resolved Pseudomonas corneal ulcer with scleral extension after prolonged systemic ciprofloxacin treatment.

Streptococcal infections can cause severe suppurative keratitis, especially in eyes with preexisting ocular surface disease (Fig. 1.47). Less commonly, streptococcal infections have a crystalline appearance without inflammation (Fig. 1.48). Although gram-negative infections usually are more serious than gram-positive infections, severe streptococcal infections can be as serious as Pseudomonas ulcers. Crystalline keratopathy caused by Streptococcus occurs in patients on topical corticosteroids, usually after penetrating keratoplasty.

Moraxella is a relatively common cause of ulcers in eyes with preexisting surface disease and in debilitated patients. The organism tends to grow slowly, the ulcer tends to respond slowly to treatment, and perforations are more common than with other organisms (Fig. 1.49A,B).

Figure 1.47. Streptococcal infection can be associated with severe suppuration.

The standard treatment of corneal ulcers includes immediate, intensive treatment every 15 to 30 minutes with broad-spectrum fortified antibiotics (i.e., tobramycin or gentamicin 15 mg/mL and cefazolin 50 mg/mL or vancomycin 12 to 25 mg/mL) or one of the fluoroquinolones, ciprofloxacin or ofloxacin. Corneal smears and cultures usually are not performed for small ulcers, but are indicated in large ulcers (>1 to 2 mm), ulcers not responding to initial treatment, and when an unusual organism is suspected by the history or appearance. Many prefer fortified antibiotics for severe ulcers requiring hospitalization and fluoroquinolones for less serious infections treated on an outpatient basis. Antibiotics are modified on the basis of culture results and gradually tapered as the infection responds. Systemic therapy is indicated only for perforated ulcers, those with scleral extension, and gonococcal infections.

Nocardia and atypical mycobacteria are uncommon



causes of indolent corneal ulcers (Figs. 1.50, 1.51A,B). Both are acid-fast organisms present in the soil. Both infections can develop weeks after injury with vegetable-contaminated matter. Atypical mycobacterial infections have been associated with inadequate sterilization of surgical instruments. Both infections are slowly progressive, often recalcitrant to medical treatment. Diagnosis is aided by the addition of acid-fast stains to the standard Gram and Giemsa stains. On the Gram stain, the organisms can be confused with gram-positive rods and thought to be diphtheroids. Lowenstein-Jensen culture media are used to isolate atypical mycobacteria. Both types of infections are treated with fortified amikacin drops. Topical and/or oral clarithromycin is also used in atypical mycobacteria infections.

Figure 1.48. Streptococcal infection can be associated with crystalline keratopathy without significant inflammation, usually in patients who are on a regimen of topical steroids after corneal transplantation.

Figure 1.49. A: Moraxella ulcers are associated with dense, full thickness corneal infiltrates. B: In this case, the cornea perforated, and the anterior chamber is flat. Blood tinged infiltrate and radial folds towards the ulcer are signs associated with perforation.

Figure 1.50. Nocardia infection developed in this patient after a partial-thickness laceration at the time of a farm-related injury. (From Donnenfeld ED, Cohen EJ, Barza M, Baum J. Treatment of Nocardia keratitis with topical trimethoprim-sulfamethoxazole. Am J Ophthalmol 1985;99:602, with permission.)

Figure 1.51. A: This recalcitrant corneal ulcer was diagnosed by corneal biopsy and cultures to be caused by atypical mycobacteria. B: This severe atypical mycobacteria infection occurred following laser in situ keratomileusis.

Fungal Keratitis

Fungal corneal ulcers are caused by a wide variety of filamentous organisms after trauma with vegetable-contaminated matter and by Candida in eyes with preexisting ocular surface disease.

Fusarium and Aspergillus are the most commonly isolated filamentous organisms. Ulcers typically have a feathery border and satellite lesions, and the infiltrate extends beyond the epithelial defect (Fig. 1.52A,B). The physician cannot count on this typical appearance. Giemsa-stained smears and cultures on appropriate media are necessary to make the diagnosis (Fig. 1.52C). Candida ulcers look similar to bacterial ulcers and are usually not suspected on the basis of the history or clinical appearance (Fig. 1.53).

Figure 1.52. A: This corneal ulcer in a patient using extended wear aphakic soft contact lenses was caused by a filamentous fungal organism, Fusarium. B: The ulcer has a typical feathery border. C: Giemsa-stained corneal smears obtained from the patient in Figure 1.51 revealed septate, filamentous organisms.

Figure 1.53. Corneal ulcer in a patient with pseudophakic bullous keratopathy was determined by cultures to be caused by Candida albicans infection.

Fungal ulcers are less responsive to medical therapy than bacterial ulcers. The drug of choice for filamentous infections is natamycin, but drug penetration and efficacy are limited. Amphotericin (0.15%) is the drug of choice for Candida. Oral fluconazole is also used in fungal infections. Topical steroids enhance fungal infections and therefore are contraindicated. Penetrating keratoplasty is indicated for infection



that progresses despite maximal appropriate medical therapy (Fig. 1.54A-C).

Figure 1.54. A: Corneal ulcer caused by Fusarium was unresponsive to intensive, appropriate medical treatment. B: The patient underwent a large, penetrating keratoplasty (PK) to save the eye. This graft failed as expected. C: Subsequently, a smaller PK was performed successfully for visual rehabilitation in a similar patient with fungal keratitis.

Figure 1.55. The hallmark of Acanthamoeba keratitis is a ring infiltrate, which developed in this patient 2 months after the onset of symptoms. (From Cohen EJ, Buchanan HW, Laughrea GS, et al. Diagnosis and management of Acanthamoeba keratitis. Am J Ophthalmol 1985;100:390, with permission.)

Figure 1.56. A: An early manifestation of Acanthamoeba keratitis is a dendritiform epithelial lesion. B: The lesion stains with fluorescein.

Acanthamoeba Keratitis

Acanthamoeba keratitis is an uncommon parasitic infection associated with the use of contact lenses, inadequate lens disinfection, and exposure to contaminated water such as swimming pools. It is frequently misdiagnosed as HSV keratitis, but unlike HSV keratitis, Acanthamoeba keratitis is associated with pain that is often out of proportion to the slit lamp findings.

The hallmark of advanced Acanthamoeba keratitis is a ring infiltrate (Fig. 1.55). Earlier signs of Acanthamoeba infection include dendritiform epithelial lesions (Figs. 1.56A,B and 1.57), radial keratoneuritis, and nonspecific stromal keratitis. Advanced disease can be associated with corneal necrosis and thinning (Fig. 1.58A) and complicated by bacterial superinfection (Fig. 1.58B).

Early diagnosis is critical for increasing the success of medical treatment. The organisms can be identified on Giemsa-stained smears (Fig. 1.59) or with calcifluor white stains when epithelial disease is present. Cultures are done on nonnutrient agar with an Escherichia coli overlay or buffered charcoal-yeast extract agar.

Figure 1.57. This large, geographic, dendritiform lesion of the corneal epithelium is caused by Acanthamoeba infection.

The medications used for treatment include topical propamidine, neomycin, clotrimazole, Baquacil, and chlorohexidine. Progressive infection may require penetrating keratoplasty, but there is a definite risk of recalcitrant,


recurrent infection after surgery. Since the use of Baquacil, medical treatment is much more successful than previously.

Figure 1.58. A: Advanced Acanthamoeba keratitis can be complicated by corneal thinning and necrosis. B: Acanthamoeba keratitis can also be complicated by bacterial superinfection, in this case by Streptococcus organisms.

Figure 1.59. If there is epithelial infection caused by Acanthamoeba, the diagnosis can be made by Giemsa-stained smears that reveal the characteristic cysts.

Episcleritis and Scleritis


Inflammation of the episclera is typically a recurrent, but self-limited condition of young adults. It is usually not associated with underlying systemic abnormalities.

Episcleritis can be simple and flat (Fig. 1.60A) or nodular (Fig. 1.60B), may affect one sector or be diffuse, and may involve one or both eyes. Nodules are pink and can be moved slightly over the underlying sclera with a cotton-tipped applicator. The cornea is typically unaffected, and patients notice mild-to-moderate ocular redness and pain.

A systemic workup is usually not indicated for episcleritis. It usually resolves without treatment. More severe cases can be treated with topical steroids and systemic nonsteroidal antiinflammatory agents such as aspirin or ibuprofen.

Figure 1.60. A: Diffuse episcleritis in the superior perilimbal area. The conjunctival redness blanched with 2.5% phenylepinephrine, leaving the darker, radial episcleral vessels apparent. B: Nodular episcleritis. A slightly mobile, moderately tender, elevated nodule is evident, typically with overlying conjunctival injection.

Figure 1.61. Anterior scleritis. The sectorial, diffuse area of scleral inflammation was moderately painful and did not blanch in response to instillation of a 2.5% solution of phenylepinephrine.

Anterior Scleritis

Anterior scleritis involves inflammation of the sclera, overlying conjunctiva, and episclera. Half of the patients with scleritis have an identifiable underlying systemic illness associated with the scleritis.

Anterior scleritis is divided into diffuse (i.e., flat, widespread inflammation; Fig. 1.61), nodular (i.e., localized, immovable, tender nodules; Fig. 1.62), and necrotizing forms (i.e., associated with thinning of the sclera). Necrotizing scleritis can occur with inflammation, which is quite painful and often associated with a systemic inflammatory disease such as Wegener's granulomatosis (Fig. 1.63), or can occur without inflammation, a form that is relatively painless and occurs primarily in patients with severe rheumatoid arthritis (Fig. 1.64). Sometimes, scleritis can be infectious and associated with corneal ulceration (Fig. 1.65). There can be extreme thinning of the sclera, even to the point of perforation.

Figure 1.62. Nodular scleritis is associated with painful, localized swelling and elevation of the episclera and sclera.

Figure 1.63. In necrotizing scleritis, there is localized episcleral and scleral inflammation with scleral necrosis and thinning. In this case, the scleritis is associated with peripheral keratitis.

Figure 1.64. Scleromalacia perforans is a noninflammatory form of necrotizing scleritis characterized by scleral thinning, usually occurring in patients with advanced rheumatoid arthritis.

Figure 1.65. Scleral infections can be caused by an extension of corneal infection into the sclera. This case, caused by streptococcal infection, occurred several days after cataract surgery and resulted in loss of the eye.


A systemic workup typically includes a physical examination and determinations of a complete blood count, erythrocyte sedimentation rate, urinalysis, fluorescent treponemal antibody (FTA-ABS) test for syphilis, rheumatoid factor, antinuclear antibody test (ANA), antineutrophil cytoplasmic antibody test (ANCA), and purified protein derivative test (PPD). Scleritis can be treated with systemic nonsteroidal antiinflammatory agents. More severe scleritis, especially necrotizing scleritis, requires systemic steroids and sometimes requires cytotoxic agents. Topical steroids are ineffective. Subconjunctival steroid injections are usually contraindicated, but recent reports suggest they may be effective and not a risk factor for perforation. Rarely, surgery is necessary to preserve the globe.

Noninfectious Corneal Disease

Dry Eye Syndrome

Dry eye syndrome is a condition in which the tear film does not adequately coat the conjunctiva and cornea. It may result from a decreased quantity of otherwise normal tears or an abnormal quality of the tear film causing increased evaporation.

The primary symptoms include ocular burning and foreign body sensation. The symptoms are usually exacerbated by prolonged use of the eyes and by environmental factors such as wind, heat, smoke, and low humidity. Paradoxically, patients may complain of excess tearing if the eye becomes so irritated that reflex tearing mechanisms are activated. A decreased tear lake and a decreased tear film breakup time are common. Other signs include punctate fluorescein or rose bengal staining of the cornea and conjunctiva, typically inferiorly or in the interpalpebral zone (Fig. 1.66A). Excess mucus, filaments, or both may be seen. A Schirmer's test performed with the patient's eye anesthetized, typically reveals reduced baseline tear secretion (<5 mm).

Figure 1.66. A: Dry eye syndrome is revealed by rose bengal staining of the interpalpebral cornea and conjunctiva. B: Silicone plug is present in the inferior punctum.


The numerous underlying causes that should be considered include systemic medications, such as antihistamines and oral contraceptives; collagen vascular diseases, such as Sj gren's syndrome and rheumatoid arthritis; ocular cicatricial pemphigoid; Stevens-Johnson syndrome; and vitamin A deficiency. A stepwise approach to treatment is appropriate, beginning with regular artificial tear drops several times a day for mildly dry eyes. For moderate dry eye syndrome, preservative-free tears are used up to every 1 to 2 hours during the day, with artificial tear ointment use at night. In severe cases, more viscous drops, more frequent applications of ointment, and temporary or permanent punctal occlusion by plugs or cautery are used (Fig. 1.66B). Lateral tarsorrhaphy may be required if less aggressive therapy fails.

Filamentary Keratopathy

Filaments are strands of epithelial cells and mucus attached to the surface of the cornea at the end of the strand (Fig. 1.67). Filaments are typically caused by corneal surface disease, most commonly dry eye syndrome. Other causes include superior limbic keratoconjunctivitis, recurrent erosions, bullous keratopathy, and patching. Patients have a red eye and complain of moderate-to-severe pain and foreign body sensation. The filaments stain with fluorescein and the unattached end moves with blinking.

Figure 1.67. In filamentary keratopathy, strands of epithelial cells intertwined with mucous debris are attached to the cornea. The filaments stain with fluorescein.

Filaments may be removed with fine forceps or a cotton-tipped applicator after topical anesthesia. The underlying condition should be appropriately treated. Lubrication with preservative-free artificial tear drops and treatment with topical acetylcysteine (10%) usually works well. Punctal occlusion is indicated when filaments are secondary to severe dry eyes, and temporary punctal occlusion may be helpful in superior limbic keratitis. Occasionally, a bandage soft contact lens may be tried for filamentary keratitis in the absence of dry eyes.

Exposure or Neurotrophic Keratopathy

Exposure keratopathy results from inadequate eyelid closure that causes corneal drying. It often occurs in conjunction with neurotrophic keratopathy, which is corneal surface disease


secondary to decreased corneal sensation. Patients with exposure keratopathy typically complain of mild-to-moderate pain and foreign body sensation, but patients with neurotrophic keratopathy have few symptoms. Superficial punctate fluorescein staining is found in the area of the palpebral fissure and in the lower one third of the cornea. The conjunctiva is often injected and may also stain with fluorescein or rose bengal. More advanced cases can have corneal infiltration, ulceration, or perforation (Fig. 1.68).

Figure 1.68. Exposure keratopathy can be complicated by an inferior corneal epithelial defect, in this case due to a Bell's palsy in a diabetic patient who also had decreased corneal sensation.

The underlying cause of the exposure (e.g., eyelid deformity, proptosis from thyroid disease) or neurotrophic keratopathy (e.g., acoustic neuroma) should be evaluated and treated. Mild conditions can be managed with artificial tear drops and ointments, and more advanced conditions may require eyelid taping at bedtime, patching, tarsorrhaphy, or conjunctival flap surgery.

Ocular Rosacea

Rosacea is a chronic, inflammatory condition that mainly affects the skin of the face. Patients develop mild-to-severe erythema along with telangiectasias and papules of the cheeks, nose, and forehead (Fig. 1.69A). Similar features can develop on the eyelid margins (Fig. 1.69B), affecting the meibomian gland secretions and creating ocular redness, burning, and a foreign body sensation. In more advanced cases, peripheral corneal neovascularization, infiltration, and even ulceration and perforation can occur. Rhinophyma can develop in severely affected patients, especially males.

Warm compresses, eyelid hygiene, and topical antibiotic ointment applied to the eyelid margins are the mainstays of treatment. Oral tetracycline, doxycycline, minocycline, or erythromycin can be extremely helpful in quieting the inflammation of the eyelid margins and meibomian glands. In patients requiring long-term treatment with oral medications, the initial dose is often tapered.

Figure 1.69. A: The skin changes of acne rosacea include telangiectasias, erythema, and papules of the cheeks, nose, and forehead. (Courtesy of Guy F. Webster, M.D., Ph.D., Philadelphia, PA.) B: Eyelid margin telangiectasias are typically seen in ocular rosacea.

Figure 1.70. One month after the acute onset of Stevens-Johnson syndrome, there is still active conjunctival and corneal inflammation and already significant symblepharon formation.

Stevens-Johnson Syndrome

Stevens-Johnson syndrome (i.e., erythema multiform major) is a severe hypersensitivity reaction affecting the skin and mucous membranes. Precipitating factors include drugs such as penicillin, sulfa, and antiseizure medications and infections such as HSV infection or mycoplasma pneumonia.

The acute phase, which can last 6 or more weeks, is characterized by bullous eruptions of the skin (i.e., target lesions) and mucosal ulceration. Ocular manifestations include an acute pseudomembranous conjunctivitis, persistent corneal epithelial defects, and symblepharon formation (Fig. 1.70). The mortality rate can be as high as 20% to 33%. Chronic ocular findings include symblepharon, dry eye syndrome, trichiasis, corneal vascularization, scarring, erosions, and ulceration.

During the acute phase, topical steroids, antibiotics, and lubricants are used. Systemic steroids are controversial. Long-term treatment with lubrication and correction of eyelid abnormalities such as trichiasis are typically required.


Keratoprosthesis surgery can be considered for end-stage disease in patients with good optic nerve and retinal function.

Ocular Cicatricial Pemphigoid

Ocular cicatricial pemphigoid is a chronic vesiculobullous disease of mucous membranes and skin that typically has a gradual onset. Its underlying cause is most likely autoimmune, although it has also been associated with certain topical medications.

Patients with ocular cicatricial pemphigoid usually are older than 60 years of age, and more women than men are affected. It is usually bilateral, with a pattern of remissions and exacerbations. The hallmarks of ocular cicatricial pemphigoid are conjunctival symblepharon and inferior forniceal foreshortening (Fig. 1.71A). The condition often produces progressive conjunctival scarring, dry eye syndrome, trichiasis, entropion, and corneal neovascularization, scarring, and ulceration (Fig. 1.71B,C).

A diagnostic conjunctival biopsy for immunofluorescent studies can be performed. Treatment includes intensive lubrication and prevention of secondary problems from glaucoma and eyelid abnormalities. Immunosuppressant therapy with dapsone, cyclophosphamide, or methotrexate is indicated for progressive disease. The clinical course and response to treatment vary greatly.

Figure 1.71. A: The hallmark of ocular cicatricial pemphigoid (OCP) is inferior forniceal foreshortening. B: Severe symblepharon formation can create adhesions between the eyelid and cornea. C: In end stage OCP there is obliteration of the fornices and keratinization of the ocular surface.

Figure 1.72. In vitamin A deficiency, the conjunctiva is extremely dry and lacks its normal luster. Notice the absence of a normal tear lake. (Courtesy of D.E. Silverstone, M.D., New Haven, CT.)

Vitamin A Deficiency

Vitamin A deficiency, also called xerophthalmia, is seen in extremely malnourished patients or those with defective vitamin A absorption or metabolism, as after gastrointestinal surgery. A slit lamp examination reveals bilateral conjunctival and corneal dryness (Fig. 1.72). Triangular gray-white spots (i.e., Bitot's spots) can be seen on the perilimbal conjunctiva in the palpebral fissure.

Figure 1.73. A: In Maroteaux-Lamy syndrome, clouding involves the entire cornea and is full thickness. This clouding usually develops after birth. B: Successful corneal transplantation may improve vision, but visual recovery may be limited by associated conditions such as optic atrophy, which was present preoperatively in this case due to meningeal involvement that became much worse when the patient developed hydrocephalus.


The underlying cause should be evaluated and treated. Systemic vitamin A replacement therapy is often necessary. Intensive lubrication with preservative-free artificial tears and ointments is required for the surface disease.


The mucopolysaccharidoses are a family of inherited disorders of carbohydrate metabolism allowing mucopolysaccharides to accumulate in tissue. These conditions are autosomal recessive, except for Hunter's syndrome, which is an X-linked recessive condition.

Most of these disorders cause corneal clouding, retinopathy, and optic nerve disease. Sanfilippo's syndrome and Hunter's syndrome typically do not cause cloudy corneas. Corneal clouding usually involves full thickness cornea and is usually not present at birth (Fig. 1.73A). If the corneal clouding is severe, penetrating keratoplasty is recommended (Fig. 1.73B). Genetic counseling is indicated.

Figure 1.74. A: Cornea verticillata, characterized by brownish, whorl-like patterns in the epithelium, is seen in patients who have or are carriers of Fabry's disease (i.e., sphingolipidosis). B: Cornea verticillata can also be seen in patients using systemic medications such as chloroquine, hydroxychloroquine, indomethacin, and amiodarone (as in this case).


Sphingolipidoses are a family of inherited lipid storage disorders. All are autosomal recessive except for Fabry's disease, which is an X-linked recessive condition. These disorders generally affect the retina. Fabry's disease can also cause renal failure. Patients with Fabry's disease and carriers demonstrate cornea verticillata, golden brown, whorl-like lines at the base of the corneal epithelium (Fig. 1.74). Milder corneal changes can occur from medications such as chloroquine, hydroxychloroquine, indomethacin, and amiodarone. Patients with Fabry's disease can also develop conjunctival and retinal vascular abnormalities.

Because visual acuity is not affected by cornea verticillata,


no treatment is needed. Genetic counseling is recommended.


Cystinosis is an autosomal recessive metabolic defect resulting in cystine crystal deposition in tissue. The infantile form is fatal without kidney transplantation. The adult form demonstrates anterior segment crystals but not kidney disease. All patients demonstrate cystine crystals in the conjunctiva, cornea, and iris (Fig. 1.75). Severe forms also have lenticular and retinal crystals. The crystals typically do not affect visual acuity, but patients may be photophobic.

In severe cases, penetrating keratoplasty can be considered. Genetic counseling should be provided.

Wilson's Disease

Wilson's disease is an autosomal recessive degeneration of liver and kidney function that can cause neurologic damage. The primary ophthalmic finding is a Kayser-Fleischer's ring, a brownish green band of copper deposition in the deep peripheral cornea (Fig. 1.76). It typically is 1 to 3 mm wide and is deep in the peripheral cornea at the level of Descemet's membrane. It occurs first superiorly and then inferiorly and is detected earliest by gonioscopy.

The ocular findings do not require treatment. Referral to an internist and neurologist for a complete workup and treatment can be life saving.

Adrenochrome Deposits

Adrenochrome deposits are melanin-like pigment accumulations of oxidized epinephrine. They can be found imbedded in the conjunctiva, typically interiorly (Fig. 1.77). Patients usually have a history of topical epinephrine use for glaucoma.

Figure 1.75. In cystinosis, cystine crystals are apparent throughout the full thickness of the cornea. Depending on the severity of the disease, crystals can also be seen in the conjunctiva, iris, lens, and retina.

Figure 1.76. In a patient with Wilson's disease, a dense Kayser-Fleischer's ring, which is a brownish green band of copper deposition, is seen in the deep peripheral cornea.

Floppy Eyelid Syndrome

Floppy eyelid syndrome typically develops in obese patients with extremely lax eyelids, which can evert spontaneously or with minimal manipulation. Classically, the eyelids evert and rub on the pillow or sheets while the patient is sleeping.

Patients complain of ocular irritation, redness, and foreign body sensation. They have extremely lax, rubbery, redundant upper eyelids that evert with minimal force. There is a fine, diffuse papillary reaction of the upper tarsal conjunctiva (Fig. 1.78). The cornea may reveal superficial punctate staining, peripheral neovascularization, or a frank epithelial defect.

A protective plastic shield over the eyes at night can prevent the eyelids from rubbing on external surfaces. Taping the eyelids closed at night can also prevent spontaneous eversion. Occasionally, a surgical eyelid tightening procedure is required.

Figure 1.77. Adrenochrome deposits are brownish black, melanin-like pigment accumulations that are often evident in the inferior conjunctiva in patients on long-term regimens of epinephrine drops.

Figure 1.78. Floppy eyelid syndrome. The patient has an extremely lax upper eyelid that everts easily on examination and often everts spontaneously during sleep or with minimal manipulation during eye examination.


Superior Limbic Keratoconjunctivitis

Superior limbic keratoconjunctivitis is a bilateral, inflammatory condition of the conjunctiva and cornea of unknown cause that is characterized by remissions and exacerbations. Patients complain of mild to severe ocular dryness, irritation, and foreign body sensation. External examination reveals a superior sectorial conjunctivitis. Slit lamp examination demonstrates a thickened, inflamed superior bulbar conjunctiva with punctate fluorescein or rose bengal staining (Fig. 1.79). There is a fine, velvety, papillary response of the upper palpebral conjunctiva, and there is often punctate staining of the superior peripheral cornea. Filaments can be seen superiorly.

Because many of these patients have associated thyroid dysfunction, thyroid function tests should be obtained. Treatment of superior limbic keratoconjunctivitis involves a stepwise approach that includes lubrication, punctal occlusion by silicone plugs, % silver nitrate solution applications, local thermal cautery, and local conjunctival resection.

Figure 1.79. In superior limbic keratoconjunctivitis, there is superior, radial, conjunctival injection and fine staining with rose bengal.

Thygeson's Superficial Punctate Keratopathy

Thygeson's superficial punctate keratopathy is a bilateral inflammatory condition of the cornea. Its cause is unknown, and it undergoes remissions and exacerbations. Symptoms include mild-to-moderate light sensitivity and foreign body sensation, with or without mildly decreased vision. Slit lamp examination reveals a noninflamed conjunctiva. The cornea demonstrates small, punctate, white, slightly elevated, snowflake-shaped epithelial and subepithelial opacities that usually have mild superficial staining (Fig. 1.80).

In mild cases, artificial tear drops may significantly improve the symptoms. Most patients require a tapering dose of mild topical steroids to control the symptoms, and occasionally, a bandage soft contact lens is used.

Terrien's Marginal Degeneration

Terrien's marginal degeneration is a slowly progressive, unilateral or bilateral, essentially noninflammatory, peripheral corneal thinning disorder seen more commonly in men.

The patients' eyes are white, typically with no history of inflammation or an epithelial defect. Vision may be decreased from irregular astigmatism. Slit lamp examination reveals a mildly to severely thinned peripheral cornea, which usually begins superiorly and can spread nasally and temporally. There are commonly lipid deposits at the leading edge of the vascularized, thinned cornea (Fig. 1.81).

The primary problem is decreased vision from irregular astigmatism, which can usually be successfully treated with a rigid gas-permeable contact lens. Rarely, the thinning is so


severe that perforation with mild trauma is possible. In such cases, a lamellar corneoscleral graft may be required for tectonic purposes.

Figure 1.80. In Thygeson's superficial punctate keratopathy, small, white, slightly elevated, snowflake epithelial or subepithelial opacities are evident. These opacities usually stain with fluorescein.

Figure 1.81. Superior, mildly vascularized corneal thinning with lipid at the leading edge is characteristic of Terrien's marginal degeneration.

Mooren's Ulcer

Mooren's ulcer is a unilateral or bilateral, chronic, progressive, painful thinning and ulceration of the peripheral cornea. The underlying cause is unknown.

Mooren's ulcers typically begin in the nasal or temporal periphery or both areas. The ulceration can progress rapidly circumferentially and centrally, with an undermined leading edge (Fig. 1.82). It may progress more slowly toward the sclera. The ulceration may go down to Descemet's membrane and may lead to perforation. Older patients tend to have a more benign form that involves only one eye and responds well to treatment. Younger patients, many of whom are of African descent, tend to have a more aggressive form of the disease that involves both eyes and is minimally responsive to treatment.

Figure 1.82. A severe, painful, peripheral corneal ulcerative process with an undermined leading edge and peripheral neovascularization is typical of a Mooren's ulcer. The underlying cause is unknown.

The workup, which is similar to that for scleritis, attempts to identify an underlying cause. Ocular treatment, depending on the severity, includes topical lubricants, topical antibiotics, topical and systemic steroids, and other immunosuppressive agents, such as cyclophosphamide or methotrexate. Surgical options include conjunctival resection, cryotherapy, conjunctival flap, cyanoacrylate glue, and lamellar or penetrating keratoplasty.

Rheumatoid Melt

Unilateral or bilateral peripheral corneal ulceration can develop in patients with collagen vascular diseases. Slit lamp examination reveals a peripheral or occasionally a central corneal epithelial defect and ulceration. There may be mild-to-moderate associated inflammation (Fig. 1.83). If the epithelial defect does not heal, the ulceration can become larger and deeper and even progress to perforation.

The underlying collagen vascular disorder should be treated. The goal of ocular treatment is to decrease inflammation and heal the epithelial defect. Healing is typically accomplished using topical lubricants or antibiotics, and occasionally using systemic steroids and other immunosuppressive agents. Punctal occlusion and temporary or permanent lateral tarsorrhaphy can work well to heal the epithelium. Tissue adhesive or corneal surgery may be needed if other treatments fail.


Megalocornea is considered to be nonprogressive corneal enlargement (>13 mm horizontally), not the result of congenital glaucoma. It is usually bilateral. Because it is an X-linked recessive disorder, it is found mostly in males.

The enlarged cornea is clear and has a normal thickness (Fig. 1.84). The enlarged corneal ring stretches the zonular fibers and predisposes the eye to develop a subluxed lens, glaucoma, or both. Routine follow-up examinations are required,


especially monitoring for lens and glaucoma problems.

Figure 1.83. A peripheral corneal ulceration to the level of Descemet's membrane superiorly is found in this patient with rheumatoid arthritis and is known as a rheumatoid melt.

Figure 1.84. Megalocornea is a clear cornea with a horizontal diameter greater than 13 mm that is not the result of congenital glaucoma. The enlarged corneal ring predisposes the eye to develop a subluxed lens or glaucoma.


Microcornea exists when the horizontal corneal diameter is less than 10 to 11 mm. It can be unilateral or bilateral, autosomal dominant or recessive, and found in males and females.

The microcornea can be clear or cloudy (Fig. 1.85). These corneas are associated with hyperopia, because the corneas are often flat. The anterior chamber angles are crowded, predisposing the patient to angle closure glaucoma, but microcornea is also associated with open angle glaucoma. Routine follow-up examination is required, especially to monitor for glaucoma.


Sclerocornea involves nonprogressive scleralization of the peripheral or entire cornea. It is usually bilateral and occurs in males and females. The scleral tissue masks only the limbus in mild cases and the entire cornea in severe cases (Fig. 1.86). The cornea is typically flat, with approximately the same curvature as the sclera.

Figure 1.85. Microcornea is a small cornea that measures less than 10 to 11 mm horizontally. This patient's cornea was 9 mm in diameter.

Figure 1.86. Sclerocornea is associated with greater corneal opacification peripherally than centrally.

Glasses or contact lenses can be used if the central cornea is clear to correct hyperopia associated with central corneal flattening. A corneal transplant can be attempted if the visual axis is involved. The prognosis for graft survival is worse than for Peters' anomaly, but has improved with the use of topical cyclosporine postoperatively.


Kerectasia is a rare, severe ectasia of the cornea. It is probably not a developmental abnormality but is instead a result of an intrauterine corneal infection with corneal ulceration and often perforation. Fortunately, most cases are unilateral. The cornea is opaque and severely ectatic, bulging through the eyelid fissure and extending anterior to the eyelid margins (Fig. 1.87). Anterior segment reconstruction can be attempted, but the prognosis is extremely poor.

Figure 1.87. Kerectasia. This severe, anterior staphyloma was probably caused by an intrauterine corneal infection with ulceration and possible perforation.


Developmental Angle Anomalies

Posterior Embryotoxon

Posterior embryotoxon is a prominent, slightly anteriorly displaced Schwalbe's ring. It is a variant of normal and does not have significant sequelae. A white, slightly irregular line just anterior to the limbus on the posterior cornea is seen on slit lamp examination (Fig. 1.88). It may be present in only a portion (several clock hours) of the cornea. No treatment is required.

Axenfeld's Anomaly and Syndrome

Axenfeld's anomaly is posterior embryotoxon with adherent iris stands (Fig. 1.89). Axenfeld's syndrome is Axenfeld's anomaly and glaucoma, which occurs in one half of the patients with Axenfeld's anomaly. Both conditions are autosomal dominant.

Peripheral iris processes are connected to a prominent, anteriorly displaced Schwalbe's ring (Fig. 1.90). If these are excessive, the angle is compromised, and glaucoma develops. Corneal edema may occur, probably caused by a decrease in the endothelial cells that migrate down the iris processes.

Routine follow-up examinations are needed, especially to monitor for corneal edema and glaucoma.

Rieger's Anomaly and Syndrome

Rieger's anomaly is the Axenfeld's anomaly plus iris stromal atrophy. One half of these eyes develop glaucoma. Rieger's syndrome is the Rieger's anomaly plus skeletal, dental, and other abnormalities. Both conditions are autosomal dominant.

Hypoplastic areas of iris stroma accompany the iris strands to the anteriorly displaced Schwalbe's ring (Fig. 1.91A). There may be associated peripheral anterior synechiae, corectopia, and pseudopolycoria (Fig. 1.91B). Typically, the pupil appears to be pulled toward the area of peripheral anterior synechiae, with iris stromal atrophy, which can progress to stretch holes, occurring 180 degrees away. Corneal edema can occur.

Figure 1.88. Posterior embryotoxon. A prominent, anteriorly displaced Schwalbe's ring occurs in many normal eyes.

Figure 1.89. The anteriorly displaced Schwalbe's ring (i.e., posterior embryotoxon) with iris strands is prominent in this patient with Axenfeld's anomaly. An adjacent iris crypt is shown.

Routine follow-up examinations are needed, especially to monitor for glaucoma, cataract, and corneal edema.

Peters' Anomaly

Peters' anomaly is a spectrum of disorders that all include a central corneal scar with defects of the posterior cornea. One half of these eyes have glaucoma. Peters' anomaly is typically sporadic but can be inherited.

Along with the central corneal scar and abnormalities of the endothelium, Descemet's membrane, and posterior stroma, there may be iris adhesions to the posterior cornea (Fig. 1.92A,B). Occasionally, a cataract develops that may also be adherent to the posterior cornea.

Management options, which depend on severity, include observation, sector iridectomy, and penetrating keratoplasty with or without cataract and glaucoma surgery.

Figure 1.90. A gonioscopic view reveals iris strands adherent to the Schwalbe's ring in the eye of a patient with Axenfeld's anomaly. The intraocular pressure was normal in this patient.

Figure 1.91. A: Rieger's anomaly. Iris strands extending to an anteriorly displaced Schwalbe's ring are associated with a large area of iris hypoplasia. B: The same patient's other eye revealed more severe iridocorneal adhesions and areas of iris atrophy.



Corneal Abrasion

A corneal abrasion is the absence of an area of corneal epithelium that is usually caused by trauma. The patient complains of mild-to-severe ocular pain, foreign body sensation, tearing, and photophobia. Slit lamp examination reveals an area of fluorescein staining of the cornea (Fig. 1.93). A corneal abrasion can be associated with eyelid swelling, conjunctival injection, a mild anterior chamber reaction, and mild miosis. Corneal stromal edema may be seen with severe or with longstanding abrasions.

Figure 1.92. A: Peters' anomaly. A dense central corneal scar and iris abnormalities are found in the patient's eye. B: The slit lamp view of the same eye reveals iris adhesions to the posterior cornea.

Treatment of routine traumatic corneal abrasions includes cycloplegia and frequent antibiotic ointment, and occasional pressure patching with a bandage soft contact lens. Corneal abrasions in contact lens wearers or those with a higher risk of infection, such as abrasions from vegetable matter or false fingernails, are treated with cycloplegia, antibiotic ointment, and no pressure patching, as pressure patching may encourage bacterial infection, particularly Pseudomonas infection. Patients are followed closely until the abrasion heals. If a corneal infiltrate develops, corneal smears and cultures and more aggressive antibiotic therapy are necessary.

Corneal Laceration

Trauma to the eye can cause a partial-thickness or full-thickness defect in the cornea (Fig. 1.94).

Figure 1.93. A large, traumatic corneal abrasion stains brightly with the cobalt blue light after topical fluorescein instillation.

Figure 1.94. This eye demonstrates a peripheral corneal laceration with a formed anterior chamber. However, because it was Seidel-positive with poorly opposed wound edges, it was emergently surgically repaired.


A Seidel test is used to help determine whether a laceration involves the partial or full thickness of the cornea. The area in question is painted with fluorescein dye and examined at the slit lamp with the cobalt blue light to determine if aqueous is leaking out, causing fluorescence or a lightening of the yellow-green dye. Trauma severe enough to cause a corneal laceration may also lead to iris prolapse, scleral laceration, cataract formation, and hyphema.

Corneal lacerations can be treated with observation or surgical repair, depending on the size and depth of the laceration and on associated ocular damage. Generally, large partial-thickness and most full-thickness corneal lacerations are surgically repaired. Patients with full-thickness corneal lacerations are treated with several days of systemic antibiotics to prevent endophthalmitis.

Corneal Foreign Body

A corneal foreign body can result from minor or more severe corneal trauma. Patients complain of ocular redness, pain, light sensitivity, and a foreign body sensation. A foreign body is detected by slit lamp examination.

Surface foreign bodies, such as a seed cover or an insect wing, can be easily removed with fine forceps while using the slit lamp. Deeper foreign bodies also may be removable using the slit lamp. However, very deep and full-thickness foreign bodies are best removed in the operating room (Fig. 1.95). Antibiotics and follow-up evaluations are important to prevent corneal and intraocular infection.

Corneal Rust Ring

Metal corneal foreign bodies can rapidly deposit rust in the underlying and surrounding corneal tissue. A reddish brown, circular opacity in the anterior stroma has an overlying epithelial defect (Fig. 1.96).

The metal foreign body should be removed first. Occasionally, the rust ring can be removed in one piece with a foreign body spud or 23-gauge needle. More often, the rust ring should be removed with a small hand-held rust ring drill. The corneal abrasion is then treated and followed to ensure healing.

Figure 1.95. Corneal foreign body. The end of a thorn is apparent deep in the corneal stroma. Because it did not perforate Descemet's membrane, this eye was not Seidel-positive.

Chemical Burn

Chemical burns may be caused by acids or alkali. Injuries from either can be mild or severe. Alkali tends to penetrate the cornea more rapidly and cause more severe corneal and intraocular damage than acid.

The clinical manifestations of chemical burns vary from mild conjunctivitis to superficial punctate keratopathy to epithelial erosions, which can lead to corneal opacities and corneal perforation, depending on the severity of the injury (Fig. 1.97). There also can be mild to extensive damage of the conjunctiva and eyelids.

No matter how severe the burn, immediate treatment includes copious irrigation and removal of any particulate matter. After a neutral pH has been reached, topical antibiotics, lubricants, and often topical steroids are used to prevent infection and aid in reepithelialization. Antiglaucoma medicines are used when needed.

Figure 1.96. Corneal rust ring. A small, reddish brown, circular opacity remained in the cornea after the removal of an iron foreign body.

Figure 1.97. Alkali burn. Significant corneal, conjunctival, and scleral damage occurred after a severe alkali injury. Notice the opacified cornea and the conjunctival and scleral blanching, indicating severe damage to the surrounding blood vessels.


Topical steroids should be discontinued after 7 to 10 days because they can promote corneal melting and perforation. Close follow-up is required until reepithelialization has occurred. Long term corneal defects (weeks to months) have been treated with oral tetracycline, fibronectin, nerve growth factor and autologous serum, among others, in experimental designs.


A hyphema is defined as blood in the anterior chamber, most commonly from blunt or penetrating trauma or intraocular surgery.

A microhyphema is composed of red blood cells suspended in the aqueous fluid, and a frank hyphema is the layering of blood or a clot in the anterior chamber. There can be associated conjunctival, corneal, iris, and scleral damage (Fig. 1.98A). A longstanding hyphema, especially in an eye with compromised corneal endothelium or elevated intraocular pressure, may cause blood staining of the cornea. Blood staining clears from the periphery of the cornea but can take months (Fig. 1.98B).

Figure 1.98. A: In hyphema, a blood clot is in the anterior chamber after a corneal laceration with damage to the iris. B: Central, red-brown corneal blood staining is clearing from the periphery months after a complete hyphema.

Figure 1.99. Oblique breaks in Descemet's membrane are evident using retroillumination. The trauma was caused by forceps used during delivery.

Postoperative hyphemas tend to resolve without rebleeding. Traumatic hyphemas from blunt trauma are treated with bed rest, atropine drops, oral antifibrinolytic agents such as aminocaproic acid, and occasionally with topical steroids to prevent rebleeding. The intraocular pressure should be monitored and treated if elevated. Patients with hyphema who are sickle disease positive or trait positive are at greater risk for the development of complications and should be monitored carefully. Hyphema patients are at risk for developing angle recession glaucoma in the future.

Birth Trauma

A mechanical forceps injury to the cornea during delivery can cause a break in Descemet's membrane, leading to corneal edema. It is usually unilateral. Corneal stromal edema is evident within days of a forceps-assisted birth. Descemet's membrane breaks are typically vertical or oblique (Fig. 1.99). The corneal edema generally clears over weeks to months but may recur many years later.

Cycloplegic and hypertonic agents can be used for symptomatic relief. After the edema clears, the eyes often reveal


myopic astigmatism, which can cause amblyopia if not appropriately treated.

Epithelial Corneal Dystrophies

Cogan's Microcytic Dystrophy

Cogan's microcytic dystrophy is an anterior corneal dystrophy affecting the epithelium and epithelial basement membrane. It is part of the spectrum of dystrophies known as epithelial basement membrane corneal dystrophies. This dystrophy may be inherited, although it can also occur spontaneously.

The intraepithelial cysts range in size from barely discernible pinpoint spots to larger, oval, and irregularly shaped cysts, all within the corneal epithelium (Fig. 1.100). The cysts consist of cytoplasmic and nuclear debris and may be found in all layers of the corneal epithelium. They are usually centrally located, unilateral or bilateral, and do not incite corneal vascularization or associated stromal haze (Fig. 1.101). They are recognized as part of a dystrophic process involving the basement membrane of the corneal epithelium. When the cysts are numerous, large, and present in the visual axis, they may cause blurred vision from irregular astigmatism. Patients who have these cysts are more prone to recurrent corneal erosions if their corneas are damaged, and they may also suffer spontaneous corneal erosions. The cysts are accompanied by map-like or fingerprint lines that are fine, linear changes surrounding the cysts.

When the cysts are few and small, they cause no symptoms. When they are larger and accompanied by maps and fingerprints in the visual axis, blurred vision occurs. Lubricating drops, such as artificial tears, during the day and ointment at bedtime may make the slightly symptomatic (from erosions) patient comfortable. If the cysts are more numerous, if they affect vision, or if there are recurrent erosions, mechanical debridement of the epithelium, cysts, and the underlying basement membrane is important. If the basement membrane is left, the cysts may recur. If mechanical debridement is not helpful and the patient suffers from recurrent erosions, anterior stromal reinforcement (puncture) is sometimes performed. Excimer laser phototherapeutic keratectomy just into Bowman's membrane, approximately 5 to 8 m deep, has been successful.

Figure 1.100. Cogan's microcystic dystrophy is composed of intraepithelial microcysts appearing as tiny, milky white dots. The microcysts appear against a background of map-like changes.

Figure 1.101. A close-up view of an area of Cogan's microcysts shows a pinpoint microcyst, a slightly larger intraepithelial milky white microcyst, and several large geographic figures that are also microcysts. In this patient, this condition caused a slightly elevated epithelium and irregular astigmatism with blurred vision, because the visual axis was involved.

Map-Dot Fingerprint Dystrophy

The map-dot fingerprint dystrophy is an anterior, epithelial basement membrane dystrophy that includes Cogan's microcysts (i.e., the dots), map-like changes produced by areas of basement membrane present within the epithelium, and fingerprints, which are parallel rows of basement membrane within the epithelium (Figs. 1.102 and 1.103).

The dots, or Cogan's microcysts, are intraepithelial, milky cysts that occur at the edge of grayish, fine map lines.


Usually, maps occur without the microcysts. The microcysts represent desquamating epithelial cells that are entrapped beneath the abnormal basement membrane sheets within the epithelium, preventing these cells, which later form cysts, from sloughing. The parallel thickening of basement membrane in adjacent rows forms the fingerprint lines.

Figure 1.102. A close-up view of the map-like changes that represent the pattern of the basement membrane within the corneal epithelium. This condition may slightly elevate the corneal epithelium and, when in the visual axis, cause irregular astigmatism and blurred vision.

Figure 1.103. Part of the map-dot fingerprint changes can be seen in retroillumination against the dilated pupil. Parallel rows of thickened basement membrane in a map-like pattern give it a fingerprint-like appearance.

With minimal map-dot fingerprint changes in the visual axis, lubricating drops and a bland ointment at bedtime are all that is required. In many cases, patients with mild map-dot fingerprint alterations of the superficial cornea need no treatment. When the changes are in the visual axis and obscure vision, mechanical debridement is the treatment choice. If there are recurrent corneal erosions associated with this disease, anterior stromal reinforcement (puncture) is sometimes helpful to enhance adhesion of the epithelium to prevent the erosions. For the most part, patients with map-dot fingerprint dystrophy can be observed. Lubricating ointments may be all that is required for minor symptoms. In more severe cases, excimer laser physiotherapeutic keratectomy or anterior stromal puncture is used. This is a self-limited disease that occurs in patients between 20 and 60 years of age, and it is seldom symptomatic in patients older than 60 years of age.

Meesmann's Dystrophy

Also called juvenile epithelial corneal dystrophy, Meesmann's dystrophy is a disorder of the corneal epithelium that is inherited in an autosomal dominant pattern. Multiple, fine, pinpoint or small cysts are seen in the corneal epithelium. Pathologic analysis reveals a fibrogranular, peculiar substance that stains for mucopolysaccharide within the epithelial cells.

The epithelial cysts are numerous, occurring almost from limbus to limbus, and do not affect the stroma (Fig. 1.104). The cysts are seen early in life, are usually stationary, and cause minor interference with visual acuity. Patients may develop recurrent corneal erosions, for which mechanical debridement is sometimes helpful. The cysts recur with regeneration of the epithelium. Lubricating drops or ointment is usually all that is needed for this very mild dystrophy. Lamellar corneal transplantation and superficial keratectomy are unnecessary. The use of soft contact lenses has been helpful in some cases but is usually not required.

Corneal Dystrophies of Bowman's Layer

Reis in 1917 and Bucklers in 1949 described a dystrophy that was dominantly inherited and usually appeared in the first decade of life. Painful corneal erosions and moderately to significantly reduced vision were the main symptoms. Unfortunately, histopathology was not included in their reports. This dystrophy consisted of geographic opacities in the region of Bowman's layer and superficial stroma. Recurrent corneal erosions were common and occurred with significant pain in the first and second decades of life. Eventually, scarring ensued with corneal anesthesia, which led to marked decrease in vision. Reis-Bucklers' corneal dystrophy is now considered by many authors to be the same as a superficial variant of granular dystrophy. It is still confused with the honeycomb dystrophy of Thiel and Benhke.

There are two schools of thought concerning these changes. First, those who tend to lump them all together and call them variants of the same dystrophy (Reis-Bucklers'), and those who separate them. These dystrophies involving Bowman's layer generally have similar symptoms and are treated alike. Light and electron microscopy have helped in differentiating these dystrophies of Bowman's layer. The clinical course and light and electron microscopic findings have recently been reviewed by Kuchle and colleagues. They feel the dystrophies involving Bowman's layer should be divided into two groups: first, corneal dystrophy of Bowman's layer type I (CDB-I), which is the true Reis-Bucklers'


dystrophy and also has been called the superficial variant of granular dystrophy; and corneal dystrophy of Bowman's layer type II (CDB-II), or the honeycomb dystrophy, which was originally described by Thiel and Benhke.

Figure 1.104. Meesmann's corneal dystrophy, which is best viewed in retroillumination against the dilated pupil, produces multiple, pinpoint cysts within the corneal epithelium. These cysts usually do not cause significant visual loss and do not stain with any diagnostic dyes.

Figure 1.105. CDB-I or true Reis-Bucklers' corneal dystrophy. This also has been called superficial variant of granular dystrophy because of the rod-like granules noted in the superficial cornea in the region of Bowman's layer and superficial stroma.

CDB-I is characterized by an autosomal dominant inheritance pattern with frequent recurrent corneal erosions starting early in life, leading to marked visual loss (Figs. 1.105, 1.106, and 1.107). The corneal dystrophy of Bowman's layer type II (CDB-II) (honeycomb-shaped or Thiel-Benhke's dystrophy), has a similar inheritance pattern and similar symptoms, but visual loss starts a little later in life and may not be as severe (Figs. 1.108 and 1.109).

The light microscopy findings in CDB-I consist of granular deposits in the region of Bowman's layer compared to CDB-II, where there was a fibrocellular, avascular, undulating layer giving the appearance of saw-tooth configuration between the epithelium and the stroma and replacing, for the most part, Bowman's layer. This did not stain very well with Mason's trichrome in CDB-II but was markedly positive in CDB-I or the true Reis-Bucklers' dystrophy (superficial variant of granular dystrophy).

Figure 1.106. Recurrence of CDB-I after a corneal transplant. Notice the marked irregularity of the light reflex and the wavy pathology in the region of Bowman's layer. This patient required phototherapeutic keratectomy for visual recovery.

Figure 1.107. Following excimer laser phototherapeutic keratectomy, this patient had a recurrence of CDB-I true Reis-Bucklers' corneal dystrophy or superficial variant of granular dystrophy. Repeat excimer laser phototherapeutic keratectomy can be done as the pathology is superficial and the laser does not ablate into the deeper cornea. Eventually, a lamellar corneal transplant and possibly a penetrating corneal transplant may be necessary in a few patients.

Electron microscopy differentiated these two entities involving Bowman's layer quite well. In CDB-I, there were rod-shaped granules present in the region of this pathology replacing Bowman's layer similar to the rod-shaped bodies in classical granular corneal dystrophy. In CDB-II, the subepithelial presence of an atypical peculiar collagen substance or curly filaments characterizes this dystrophy. This is now considered to be the honeycomb-shaped dystrophy of Thiel-Benhke.

In the early stages of both CDB-I and CDB-II, treatment consists of lubricating drops, patching, occasional bandage soft contact lenses, and antibiotic ointment to prevent infection. In the first decade of life when these dystrophies first occur, visual acuity is usually good between the episodes of


corneal erosions. In the second and third decades, as scarring occurs, vision becomes more blurred and surgical treatment is necessary. Superficial kerectomy has been done to remove the scarring in the region of Bowman's layer. Usually a very superficial portion of the stroma is removed along with Bowman's layer and epithelium. It is generally easy to find a superficial stromal lamella where the pathology is minimal or has not occurred, allowing for a fairly smooth dissection. Now, excimer laser phototherapeutic keratectomy is the treatment of choice for this superficial corneal disease. There is recurrence of pathology after excimer laser phototherapeutic kerectomy, but considerably better vision is achieved for 1 to 4 years with this treatment and the necessity for corneal transplantation is delayed (Fig. 1.107).

Figure 1.108. CDB-II or Thiel-Benhke's corneal dystrophy. In this dystrophy, also described as honeycomb-shaped, there are curly filaments in the superficial cornea in the region of Bowman's layer rather than the rod-like granules typical of CDB-I.

Figure 1.109. Recurrence of CDB-II in a patient who had a corneal transplant for severe dystrophic changes involving the superficial as well as the midcornea. This patient was first thought to have Reis-Bucklers' dystrophy but light and electron microscopy eventually revealed that curly filaments were present in the region of Bowman's layer and this represents CDB-II or Thiel-Benhke's honeycomb dystrophy. The treatment as in CDB-I is excimer laser phototherapeutic keratectomy and then when sufficient stroma is involved, either lamellar or penetrating corneal transplantation.

Eventually, the disease recurs despite the dissections and excimer laser treatments, and either a lamellar or penetrating keratoplasty is required (Fig. 1.109). Recurrence of disease in the corneal transplant is common for both CDB-I and CDB-II, but the visual acuity is usually better as the superficial cornea may be clearer despite recurrence of disease in the graft. It is better to do a lamellar corneal transplant first because if the disease does recur in the graft, a repeat lamellar or penetrating keratoplasty may be necessary. These corneal dystrophies involving Bowman's layer usually do not cause recurrent erosion or pain after the third or fourth decades of life, although visual loss may be considerable.

Stromal Dystrophies

Granular Dystrophy

Granular dystrophy is a dominantly inherited, fairly common, and recognizable corneal dystrophy that has varied manifestations and pathologic features. Treatment is seldom necessary in the first few decades of life as symptoms occur later as the dystrophy progresses.

Figure 1.110. In granular dystrophy, hyaline deposits are sharply demarcated in the stroma and are surrounded by clear cornea.

As with most dominantly inherited corneal dystrophies, the pathology is central rather than peripheral and does not cause inflammation or vascularization of the cornea. Characteristic of this dystrophy are clear areas between the hyaline deposits in the stroma, which allows for good vision late into the course of the disease (Figs. 1.110 and 1.111). In some families, however, the clear stroma in the middle of the pathologic areas is compromised, causing decreased vision (Fig. 1.112). Recurrent corneal erosions can occur later in the course of the disease, but much of the visual loss is caused by the stromal hyaline deposits.

A new variation of granular dystrophy, called Avellino dystrophy, has been recognized. It has amyloid deposits in addition to the hyaline stromal deposits. Several families with this unusual combination have been traced back to Avellino, Italy, for which this granular dystrophy variation was named. Symptoms are similar to those of granular dystrophy, but the corneal changes are somewhat different (Fig. 1.113). Some of the stromal opacities are more irregular and elongated. Avellino dystrophy also is dominantly inherited.

Figure 1.111. Retroillumination reveals the clarity of the stroma between deposits of hyaline in a case of granular corneal dystrophy.

Figure 1.112. Granular dystrophy with confluent opacities can lead to superficial corneal erosions and blurred vision. Notice the irregular light reflex. In this case, there is no clear space between the hyaline deposits, and vision is significantly blurred. Penetrating keratoplasty is indicated.


In the first few decades of life, no treatment is needed because vision is good and erosions usually do not occur. In some families, confluent pathology in the central cornea is found during the fourth decade and beyond. Depending on the extent of the central opacity and the response to visual correction with contact lenses and other means, penetrating corneal transplantation may be the treatment of choice. Excimer laser phototherapeutic keratectomy and lamellar keratoplasty usually are not options because of the depth of the defect in the middle and deeper stroma. Recurrence of hyaline and amyloid degeneration in the new transplant tissue is common (Fig. 1.114). The prognosis for corneal transplantation in granular dystrophy is generally excellent, with well over 90% of the corneas remaining clear for at least several years. Eventually, granular deposits may form in the superficial stroma and cause recurrent opacification and possible recurrent erosion.

The genetics of granular, lattice, and macular dystrophy have revealed that they all involve a mutation at the BIGH-3 gene.

Figure 1.113. In granular corneal dystrophy, granular-appearing amyloid and hyaline degenerative changes were found in the stroma. This is the Avellino variation of granular dystrophy seen in families whose origin can be traced to the small hill town of Avellino, Italy.

Figure 1.114. Recurrent granular dystrophy in a corneal transplant. This patient's original corneal transplant was done about 15 years before this photograph was taken. Notice the remaining granular dystrophy beyond the edge of the graft. Superficial granular deposits in the stroma have recurred. The patient still had good vision at the time of this photograph; regrafting was not indicated for another 10 years.

Lattice Corneal Dystrophy

Amyloid deposits in the cornea characterize this dominantly inherited stromal dystrophy. Recurrent erosions may occur in the fourth decade and beyond, which lead to decreased corneal sensation, scar formation, and significantly decreased vision.

Lattice corneal dystrophy is a bilateral corneal dystrophy with linear deposits of hyaline in the stroma. Patients with this dystrophy must be differentiated from patients with prominent corneal nerves and blood vessels in the cornea, both linear findings that can be confused with lattice dystrophy. The epithelium and sub-Bowman's stroma are generally spared until the fourth decade of life (Fig. 1.115) or


later, when superficial erosions and filamentary keratitis occur (Fig. 1.116). These erosions may mimic the appearance of dendritic keratitis from HSV infection. The cornea becomes anesthetic, and Bowman's membrane and superficial stroma are replaced by scar tissue. These erosions are painful, and the marked irregular astigmatism and confluent scar formation causes decreased vision. As the corneal nerves are destroyed, the cornea becomes much less sensitive.

Figure 1.115. Retroillumination of lattice corneal dystrophy. Notice the typical thick, linear pattern of amyloid degeneration in the stroma. The relatively good light reflex indicates excellent vision, and the surrounding stroma is clear in this early case of amyloid deposits in the stroma.

Figure 1.116. Recurrent erosion in lattice dystrophy shows marked filamentary keratitis and thick lattice changes. These erosions were painful and led to significant corneal scarring and the need for a corneal transplant.

Symptoms can vary in any family and between families, with later generations developing problems earlier in life. With the continued erosions and laying down of more scar tissue with each erosive episode, it may take several years to a decade or more before vision is decreased enough to warrant surgical treatment.

At first, with only stromal lattice changes, no treatment is necessary. As the superficial pannus builds up, the irregular astigmatism that occurs can be treated with a soft or rigid gas-permeable contact lens. When this is insufficient, the superficial cornea may be peeled by superficial keratectomy or phototherapeutic keratectomy with excimer laser. Eventually, these means fail because repeated keratectomy becomes too deep to provide good vision. A penetrating corneal transplant is then required. These grafts are visually successful early, but amyloid deposits recur in the new graft tissue. These deposits are first seen in the periphery where sutures were placed and are later seen in the central stroma of the donor button (Fig. 1.117). Repeat corneal transplantation is also successful, but amyloid deposits develop in subsequent grafts. Lamellar corneal transplants are an alternative to penetrating grafts if the dissection bed can be extremely smooth. Automated microtomes are being developed which will do this.

Figure 1.117. Recurrent lattice dystrophy is seen as fine deposits using retroillumination in the patient in Figure 1.116, who received a corneal transplant. About 4 years later, superficial deposits were detected in the cornea. These recurrences start along the suture tracks in the donor button and then can be seen, in some cases, in the superficial stroma.

Gelatinous Drop-like Dystrophy

Gelatinous drop-like dystrophy is another dystrophy that is caused by localized amyloid deposits. In this case, the deposits are superficial and cause visual loss early. It is a recessive disease that is usually seen in the first and second decades of life, causing severe loss of vision. There are no systemic findings associated with this amyloid dystrophy. The cornea develops multiple, confluent, epithelial and subepithelial, gelatinous, mulberry-like deposits that obscure vision (Fig. 1.118). Histopathologic analysis reveals mounds of amyloid between the corneal epithelium and Bowman's membrane and deeper deposits of amyloid in the stroma, similar to lattice dystrophy.

Superficial keratectomy is preferred over lamellar corneal transplantation or penetrating keratoplasty because the amyloid deposits and visual loss recur after each keratectomy.

Figure 1.118. Gelatinous drop-like dystrophy. The mulberry appearance of superficial corneal deposits is easily recognized by the marked broken-light reflex from the corneal surface. The appearance of localized, superficial amyloid deposits characterizes this condition, for which superficial keratectomy is preferred over lamellar corneal transplants or penetrating grafts. The disease is often recurrent.

Figure 1.119. The diffuse corneal haze with highlighted white deposits typifies macular corneal dystrophy. The dystrophy is present from limbus to limbus and in all layers of the cornea, but visual acuity is not disturbed early in the course of the disease. Penetrating keratoplasty is indicated in the later course of this recessive corneal dystrophy.


Macular Corneal Dystrophy

Macular corneal dystrophy is the only major autosomal recessive stromal dystrophy. It results from the abnormal synthesis of keratin sulfate proteoglycan, occurs early in life, and causes visual loss in the first or second decade of life. Two types of this dystrophy have been described, one with systemic involvement and one without.

With accumulation of glycosaminoglycans within stromal keratocytes, the endothelium, and the stroma, there is a diffuse limbus-to-limbus haze in all layers of the stroma (Fig. 1.119) accompanied by corneal thinning. Central, focal, white deposits are seen in the stroma against a background of variable stromal haze. These deposits become more diffuse, as does the background haze, leading to further visual loss (Fig. 1.120). Erosions do not occur, and vision may not be decreased as the corneal surface remains smooth at first. With further deposits of glycosaminoglycan and a buildup of focal, white deposits, corneal opacification increases and corneal transplantation is needed.

Figure 1.120. More severe involvement of macular corneal dystrophy than that seen in Figure 1.119, with a central corneal diffuse haze and decreased vision. Even though the light reflex is sharp, vision is decreased (20/70). Penetrating keratoplasty is indicated.

Depending on the corneal background haze and focal, white deposits, penetrating corneal transplantation may be required for better vision. Generally, corneal transplantation may take place between 10 and 35 years of age, unlike treatment for the other stromal dystrophies. Disease recurs in the new graft, but the hazy opacity appears less often and later than does the recurrence of dystrophic changes in granular and lattice dystrophy grafts. Because all corneal layers are affected with recurrences, repeat penetrating corneal transplantation may be necessary, but is less likely and occurs later than in granular or lattice dystrophies.

Crystalline Dystrophy of Schnyder

The crystalline dystrophy of Schnyder is an autosomal dominant dystrophy that is less often seen than granular, lattice, and macular stromal dystrophies. It is largely inherited from people of Scandinavian background. An early sign of this stromal dystrophy is the characteristic crystals appearing in irregular, central, ring-like deposits in the first few years after birth.

The needle-shaped crystals are first faintly seen in a central, ring-like configuration. During the first four or five decades of life, these stromal crystals do not interfere with the epithelial surface, and vision is usually good (Fig. 1.121). Arcus senilis is usually prominent but does not always accompany the crystals. Significantly elevated triglycerides and serum cholesterol may be found in some affected individuals and family members. Some affected individuals may also demonstrate genu valgum, xanthelasma, and cardiovascular problems.

With age, more cholesterol crystals are deposited in the stroma, along with triglycerides and cholesterol esters. The cornea becomes more diffusely opacified, and the entire


stroma, from limbus to limbus, is involved. The cornea takes on a more opaque whitish appearance and vision diminishes (Fig. 1.122). Corneal transplantation is generally required after age 45 years.

Figure 1.121. Although the opacity looks dense, this 28-year-old patient with Schnyder's crystalline dystrophy has 20/20 vision. The periphery of the cornea is clear, and the deposits are located in the superficial one third of the stroma.

Figure 1.122. Later in the course of Schnyder's crystalline dystrophy, the deposits become diffuse, and no portion of the cornea is spared. When vision is significantly reduced by diffuse deposits and irregular astigmatism, penetrating keratoplasty is indicated.

No treatment is required during the first decades of life because vision is usually excellent. Later, with further deposits of crystals and lipid permeating the corneal stroma, corneal transplantation is required. The transplants stay clear for many years, but cholesterol crystals, triglycerides, and cholesterol esters eventually enter the new graft and cause a haze 10 to 20 years after transplantation. Repeat corneal transplantation may be necessary and is also successful.

Figure 1.123. Central cloudy dystrophy of Fran ois produces a cloudy appearance of the stroma adjacent to Descemet's membrane. The light reflex is sharp, and these changes were noticed before the patient had an intracapsular cataract operation with sector iridectomy. This condition can be confused with Fuchs' dystrophy, but in the Fuchs' form, the stroma and the epithelium are edematous. In this case, there is no corneal thickening, and the epithelium is clear. These forms must be differentiated, because cataract surgery does not lead to corneal decompensation for central cloudy dystrophy of Fran ois as it may in Fuchs' dystrophy.

Figure 1.124. Central cloudy dystrophy of Fran ois should not be confused with posterior crocodile shagreen, shown here. In this normal, mild, corneal degeneration, there is no decompensation of the cornea and no corneal or epithelial edema. Both conditions are benign, and they can be differentiated by the linear pattern of haze in the deep cornea in posterior crocodile shagreen.

Central Cloudy Dystrophy of Fran ois

This dystrophy may be confused with posterior mosaic crocodile shagreen. Both involve the deep stroma and have somewhat similar appearances. Both are innocuous and do not interfere with vision.

Central cloudy dystrophy of Fran ois is a dominantly inherited dystrophy in some families. It mainly involves the axial cornea and occurs deep in the stroma. There are grayish, small, uniform patches with clearer areas outlining the patchy cloudy areas (Fig. 1.123).

Vision is not affected because the changes do not involve the endothelium and because the cornea is not prone to the onset of late edema after cataract surgery or even without surgery. The disease does not follow the course of Fuchs' dystrophy, with which it has been confused. The deep patchy changes of posterior crocodile shagreen, with grayish, polygonal patches of various sizes surrounded by clear lines, can be differentiated from the dystrophy of Fran ois by its crocodile-like skin pattern (Fig. 1.124).

Observation alone is indicated, because the pathologic changes of this dystrophy do not progress and do not lead to corneal clouding, edema, or vision-threatening opacity.

Endothelial Dystrophies

Cornea Guttata

Also called endothelial dystrophy, cornea guttata are mushroom-shaped excrescences or bumps on Descemet's membrane concomitant with decreased cell numbers and flattening of the endothelial cell layer. Usually, thickening of Descemet's membrane is evident and progresses, with the endothelial cells diminishing and the guttae increasing. Cornea guttata are seen more frequently with aging. They


have been described in normal populations, affecting 5% to 70%, with higher numbers for older populations. Most patients with cornea guttata do not progress to Fuchs' dystrophy.

The classic appearance is that of beaten silver pattern, which is seen with a broad slit beam by specular microscopy. The slit lamp changes are more central and seldom reach the corneal periphery (Fig. 1.125). Many patients who undergo cataract surgery have endothelial dystrophy. They do not develop Fuchs' dystrophy postoperatively but are subject to more postoperative corneal edema as their endothelial cell counts are diminished. These corneas usually clear postoperatively unless endothelial guttata are numerous and the endothelial cell count is significantly diminished before surgery.

Most persons with endothelial guttata do not progress to or develop stromal and epithelial edema. The name Fuchs is applied to the dystrophy when corneal stromal and epithelial edema occur, and the determination is based on severe endothelial dystrophy.

Observation is indicated for endothelial guttata. Because over 90% of the patients with this condition do not develop corneal edema (i.e., Fuchs' dystrophy), they should be told about the benign nature of their corneal disorder. If cataract surgery is contemplated, the patient should be told of the slight increase in postoperative problems (e.g., corneal edema) with this surgery. Phacoemulsification and extracapsular cataract extraction can lead to postoperative corneal edema if guttata are present. The edema usually clears in a few weeks after the surgery. Corneal transplantation is not required for endothelial dystrophy. Patients who have marked endothelial dystrophy and require cataract surgery but have normal corneal thickness (no edema) should not undergo a corneal transplant but should instead have only cataract surgery and posterior chamber lens implantation.

Figure 1.125. Endothelial dystrophy. Notice the beaten copper or silver appearance of the endothelium, which indicates cornea guttata changes in the corneal endothelium. The cornea was of normal thickness, and there was no epithelial edema. This condition is best seen by specular microscopy. No more than 10% of the patients with endothelial dystrophy eventually develop Fuchs' dystrophy.

Fuchs' Dystrophy

Stromal corneal swelling with evidence of epithelial corneal edema in the presence of endothelial guttata is called Fuchs' corneal dystrophy, also known as late hereditary endothelial dystrophy. Fuchs never saw cornea guttata because the slit lamp biomicroscope had not been invented, but his name remains attached to this disease because he was the first to describe it.

About 10% of cases of Fuchs' dystrophy are inherited. It is thought to be an autosomal dominant trait in some families. Fuchs' dystrophy occurs more commonly in women than men. The earliest diagnosis of Fuchs' dystrophy can be made in a patient with cornea guttata who develops stromal swelling as measured by pachymetry or where stromal swelling is noted at the slit lamp. Early epithelial edema may be seen as bedewing and may be present only on awakening because of corneal decompensation overnight, when there is no evaporation from the corneal surface because the eyelids are closed. Later in the course of the disease, when there is more confluent endothelial involvement and less endothelial cell function, epithelial and stromal edema occur continually, and vision is blurred all day. The corneal edema can develop into macroedema from the bedewing, and marked corneal irregularity can further blur vision (Fig. 1.126). The edematous epithelial cells eventually may lead to bullous keratopathy, which is usually not painful, unlike the bullous keratopathy accompanying cataract surgery (Fig. 1.127).

In the early phases of epithelial edema, hypertonic eye drops (usually sodium chloride) during the day and hypertonic ointment at bedtime may help deturgess the cornea and smooth the epithelial surface to provide better vision. Lowering the intraocular pressure with a -blocking agent can also decrease the stromal and epithelial edema. A bandage soft contact lens for daily wear can smooth the corneal


surface and provide better vision, but this is a temporizing treatment. A hair dryer held at arm's length with the warm air blown onto the cornea may more rapidly deturgess the cornea and improve vision after awakening. This also is a temporary expedient. Penetrating corneal transplantation is the only treatment when the corneal edema cannot be helped by other means and is usually successful, with better than 90% of the transplants providing clear corneas. The disease does not recur in the graft because the donor endothelium in the new graft remains intact.

Figure 1.126. Fuchs' dystrophy is seen in retroillumination as a marked irregularity of the cornea surrounded by endothelial dystrophy. The cornea was thickened to approximately 0.7 mm, but the localized corneal edema allowed vision around this corneal opacity.

Figure 1.127. Notice the epithelial macroedema, and bullous changes. The patient's vision was significantly reduced because of epithelial edema, and a penetrating keratoplasty was indicated.

Posterior Polymorphous Dystrophy

Widely variable clinical manifestations characterize this autosomal dominant dystrophy. Most patients do not require transplantation, and the disease is usually not found until later in life, when unusual single or groups of vesicles are seen on routine examination. Specular microscopy of these areas reveals the disease most clearly (Fig. 1.128).

Figure 1.128. Specular microscopy of posterior polymorphous dystrophy. Posterior polymorphous dystrophy produces areas of normal endothelium surrounded by large areas of markedly abnormal endothelium with linear drop-out of endothelial cells and large cystic areas of endothelial cell absence.

Figure 1.129. Grouped small vesicles in a patient with polymorphous dystrophy are seen using retroillumination. The endothelial changes are minimal, and this patient has normal corneal thickness and normal vision.

Clinical Features

Few cases are recognized in the first decades of life, because most patients have good vision until later. The endothelial changes are usually first seen on a routine examination, when individual (Fig. 1.129) or grouped (Fig. 1.130) endothelial vesicles are seen with the broad slit lamp beam; the vesicles are surrounded by normal-appearing endothelium. This condition is better visualized by retroillumination against the red reflex of a dilated pupil. In most cases, stromal edema and epithelial edema do not occur, but when the endothelium is compromised sufficiently, corneal stromal and epithelial edema may be seen.

About 25% of patients may develop peripheral anterior synechiae, as seen by gonioscopy. Patients with extensive peripheral anterior synechiae may develop glaucoma, which can be difficult to treat. In these cases, differentiation between the iridocorneal endothelial (ICE) syndrome must be made. Posterior polymorphous dystrophy is bilateral and dominantly inherited, but ICE syndrome is not inherited and is unilateral. All patients with ICE syndrome develop


glaucoma, although this is not the case with posterior polymorphous dystrophy.

Figure 1.130. Notice the linear vesicles in this patient with posterior polymorphous dystrophy. There was slight corneal edema over these areas of vesicles, but because most of the endothelium was healthy, the patient had relatively good vision.

Most patients with posterior polymorphous dystrophy only require observation because the few single or grouped endothelial vesicles do not cause corneal edema. If corneal stromal and epithelial edema occur, it is treated like the edema caused by Fuchs' dystrophy. For the few patients who develop severe edema from posterior polymorphous dystrophic changes, penetrating corneal transplantation is the treatment of choice. Keratoplasty for this dystrophy is highly successful if glaucoma is not present or can be controlled. The corneal transplants stay clear in more than 90% of cases, and host endothelium does not replace donor endothelium.

Congenital Hereditary Endothelial Dystrophy

Congenital hereditary endothelial dystrophy may be inherited as an autosomal dominant or recessive trait. The endothelium may be severely compromised early, leading to marked corneal edema and visual loss during the first few years of life.

This disease, which may appear at birth in some cases, must be differentiated from congenital glaucoma. In congenital hereditary endothelial dystrophy, the intraocular pressure is normal, and the cornea is not enlarged but is thickened. In other forms of this dystrophy, the cornea may be clear at birth, but decompensation occurs during the first decade, as the endothelial cells die out. The endothelial cells seen at keratoplasty are remarkably atrophic or missing and the stroma may be three times the normal corneal thickness (Fig. 1.131). No reason for endothelial cell death is known, but the nonbanded posterior part of Descemet's membrane, which usually develops after the fifth month of pregnancy, is abnormal.

Figure 1.131. In this slit lamp view, there is a markedly thickened cornea and diffuse corneal edema from limbus to limbus. This typifies congenital hereditary endothelial dystrophy, which occurred in this patient within the first few years of life and required corneal transplantation.

Penetrating corneal transplantation is the only treatment when vision is significantly reduced from stromal and epithelial edema. Keratoplasty success is reduced compared with the results for Fuchs' dystrophy and posterior polymorphous dystrophy because of the marked difference between the host and donor corneal stroma and because of the lack of host endothelial cell viability. However, the operation still provides a chance for visual improvement. The success rate varies but is about 75%.



Keratoconus is a mostly bilateral, occasionally hereditary (10%), paracentral corneal ectasia. This noninflammatory condition is a common disorder. The incidence has been estimated to be between 4 and 100 per 10,000 members of the general population. This disease occurs in both sexes equally. The marked variation in symptoms, from severe blurred vision to no visual loss despite computerized topographic evidence of keratoconus corneal changes, makes incidence reporting difficult.

Keratoconus can be associated with Down syndrome (Fig. 1.132), atopic disease, and vernal catarrh; in all cases, eye rubbing is common. It also occurs with retinitis pigmentosa, certain retinal degeneration, aniridia, and Marfan's syndrome. The earliest manifestation of keratoconus is the frequent need to change the prescription for glasses, even before there is slit lamp evidence of the disease. At this point, there is usually inferior corneal steepening, which is seen earliest with inferior keratometry or with computerized corneal topography. As the disease progresses, certain clinical signs appear, such as apical protrusion and slight thinning of the apex seen by using the slit lamp. Vogt's striae, which are folds in Descemet's membrane that disappear in response to pressure, are also a diagnostic sign (Fig. 1.133). A Fleischer's ring may be visible all around the


cone or at the base of the cone. This is an iron line that is deposited because of corneal surface irregularity. With more protrusion, apical scarring forms, which can make contact lens use more difficult. Further protrusion stretches Descemet's membrane and can cause it to rupture. Aqueous then flows into the stroma, leading to marked swelling and further loss of vision. This condition is called a corneal hydrops (Fig. 1.134).

Figure 1.132. Keratoconus in a patient with Down syndrome is revealed by a positive Munson's sign and marked central and paracentral ectasia of the cornea.

Figure 1.133. Vogt's striae occur centrally in a patient with keratoconus. By applying digital pressure on the eye while looking through the slit lamp, these striae in the deep cornea, mostly Descemet's membrane, disappear, which is characteristic of keratoconus.

Keratoconus in its early stages is managed with glasses or soft contact lenses. As the cornea irregularity becomes more pronounced, rigid gas-permeable contact lenses are needed to restore visual acuity. Approximately 90% of patients with keratoconus are managed without the need for corneal surgery. Epikeratophakic lamellar procedures had been indicated, particularly for patients with Down syndrome. Because epikeratophakic tissue is no longer commercially available, this procedure is seldom done. Lamellar keratoplasty with new microkeratomes or facilitated lamellar dissection with air or fluid is being done.

Figure 1.134. Hydrops in a patient with Down syndrome who has keratoconus. Abrupt ruptures in Descemet's membrane in severe keratoconus in response to eye rubbing may cause the aqueous to quickly expand into the stroma and cause marked swelling of the cornea, as much as five or six times the normal corneal thickness in some cases. This patient slowly improved over time, and the cornea returned to its previous configuration, although it was a little flatter and with more scarring. In most cases, hydrops resolves without surgery.

Penetrating corneal transplants are indicated when patients no longer achieve good vision with rigid gas-permeable contact lenses or are unable to wear their contact lenses. Fortunately, penetrating keratoplasty is successful in 97% of these cases, providing 20/40 vision or better. Some form of graft rejection is encountered in about one third of these corneal transplants; fewer than 2% must be repeated because of irreversible rejection.

Pellucid marginal degeneration is a variation of keratoconus in which there is marked corneal steepening and anterior protrusion of the inferior cornea near the 6-o'clock limbus. It is considerably rarer than keratoconus. Unlike keratoconus, in which the corneal steepening appears in the paracentral cornea, this ectasia occurs close to the limbus but not directly at the limbus. The central cornea remains normal until later in the disease course, and visual acuity is good. A fine inferior pannus can occur, and the cornea can protrude significantly, making contact lens wear difficult or impossible (Fig. 1.135).

A fairly steep change from normal-appearing cornea centrally to extreme thinning and anterior bowing forward near the limbus is typically seen in cases of pellucid degeneration. As with keratoconus, the early stages of pellucid degeneration are usually managed with glasses, and later with rigid gas-permeable contact lenses. As long as a rigid gas-permeable contact lens can be worn, vision is usually acceptable, because the central cornea does not usually develop scarring.

Arcus Senilis

This degenerative corneal change is typified by peripheral corneal lipid deposits in an arc or complete circle and is encountered


with aging and certain systemic diseases of abnormal lipid metabolism.

Figure 1.135. Pellucid degeneration is seen as marked steepening of the inferior cornea adjacent to but not directly at the limbus. This is a forme fruste of keratoconus with marked inferior steepening. Vision may be good until late in the course of the degeneration, because the central cornea is not ectatic. As the inferior cornea steepens, rigid gas-permeable contact lenses become more uncomfortable to wear, and the patient requires corneal transplantation.

Arcus senilis usually occurs as an aging process. It begins inferiorly and superiorly and later, but less commonly, it may encircle the cornea. It is not accompanied by peripheral corneal vascularization and is typified by a clear interval between the limbus and the lipid deposits. The lipid deposits have a more clearly defined peripheral border and a more diffuse central border (Fig. 1.136). The lipid is most concentrated in the deeper cornea near Descemet's membrane but occurs in more advanced cases in all layers of the stroma. Diseases characterized by abnormal lipid deposits include hyperlipoproteinemia I and III and corneal dystrophies such as Schnyder's crystalline dystrophy.

Observation alone is indicated, because the peripheral lipid deposits in arcus senilis and in circular senilis do not interfere with vision and do not cause peripheral thinning or degenerative changes.

Lipid Degeneration

The appearance of a whitish or yellowish, arc-like configuration in front of an area of corneal opacification with blood vessels signifies the abnormal deposition of lipid in the cornea stroma.

This secondary lipid degeneration occurs when blood vessels grow into the stroma and are associated with old stromal inflammation or infection. After the stromal inflammation heals, many vessels collapse and disappear or remain empty of blood; these are called ghost vessels. When blood persists in these blood vessels, there may be a very slow leakage of lipids from the vessel capillary wall, which deposits lipid material at the leading edge of the vascularized stroma in an arc shape (Fig. 1.137). If the lipid is peripheral, no visual consequences occur, but central lipid degeneration may cause visual loss. The lipid is deposited in all layers of the stroma.

Figure 1.136. Arcus senilis. The arc-like deposits of whitish yellow lipid are detected interiorly and superiorly, almost circumventing the limbus and leaving the lucid area that typifies arcus senilis formation.

Figure 1.137. Lipid degeneration. In this cornea, which was previously inflamed, there is an arc of yellowish deposit in front of the corneal scar opacity with feeding vessels. When blood persists in these blood vessels, there may be a very slow leakage of lipids from the capillary walls, which deposit lipid material at the leading edge of the vascularized stroma. This is lipid degeneration. As long as vision is not affected, observation alone is indicated. Closing off the vessels may slow down or stop the deposition of lipid, but in most cases, this is unnecessary.

Obstructing the flow of blood in the stromal vessels can halt further deposition of lipid temporarily. Usually, the vessels open again after being closed. These vessels can be closed by several methods, including partial removal or cutting, cautery, laser, and chemical means. Generally, peripheral secondary lipid deposits can be observed when they do not affect the visual axis. They seldom spread centrally, and vision remains good. When these deposits occur in significant amounts in the central cornea, penetrating corneal transplantation may be necessary for improved visual acuity.


A pterygium is a triangular-shaped fibrovascular, degenerative tissue growing onto the cornea. It usually begins nasally but can start temporally and grow onto normal corneal tissue. Exposure to ultraviolet light is considered to be the major cause of pterygium growth, although the precise mechanism or trigger events are unknown. Pterygia are far more common in people living within 20 degrees of the equator than in the far northern or southern regions away from the equator.

Pterygia may start out as a pinguecula in the nasal or temporal conjunctiva. The stimulus to cross the limbus and grow onto the cornea is not understood. A sheath of vessels is carried onto the cornea behind a leading edge of elastotic degeneration (Fig. 1.138).

Capillaries in the head of the pterygium may grow further onto the cornea and lead to more opacification. Areas where red blood cells are seen to accumulate at the leading edge and where they are not confined by capillary walls indicate activity of the pterygium and further progression onto the cornea. When the pterygium stops growing, an iron line, known as Stocker's line, may occur in front of it


in clear cornea. The pterygium may advance onto the cornea and then become dormant, never threatening vision, or it may proceed across the cornea and compromise the visual axis causing significantly blurred vision.

Figure 1.138. Early pterygium with vessels and the opacified pterygium head advancing onto the cornea. Observation alone is indicated when the pterygium enters the cornea. In many cases, it does not advance farther. Pterygia that are not advancing, do not affect vision, and are not cosmetic problems require observation alone.

Observation alone is indicated for early pterygia that are not cosmetically disfiguring, do not threaten the visual axis, and are not growing further onto the cornea. If pterygia removal is necessary, there are several means of removing the pterygia, but the most important consideration is preventing their recurrence, which is usually worse than the primary pterygia (Fig. 1.139). Methods to remove the pterygia that have the lowest recurrence rates are under investigation. Removing the pterygium and replacing it with a conjunctival transplant from the upper bulbar conjunctiva of the same eye is effective, with only a 5% to 10% recurrence rate. Removing the pterygium and applying beta radiation with a strontium 90 applicator has about a 20% recurrence rate. The bare sclera technique alone, without covering the pterygium bed, is no longer done. The latest means of preventing recurrence is with the use of mitomycin C, but the dose and complication rate are still being investigated.

Figure 1.139. A recurrent pterygium has grown into the previous bed and has advanced into the visual axis. Removal of this pterygium with conjunctival transplantation is necessary. A diamond burr can be used to smooth the central cornea to allow better vision. Occasionally, lamellar corneal transplantation is needed if the visual axis is compromised.


The asymptomatic appearance of yellowish lipid deposits in the conjunctiva of the nasal interpalpebral region characterizes a pinguecula. When a pinguecula advances onto the cornea, it is then called a pterygium, but a pterygium does not necessarily have to start with a pinguecula.

Pinguecula formation occurs in many older people and is considered a degenerative process. A yellowish deposit may occur in the conjunctiva nasally, near the limbus, and sometimes temporally (Fig. 1.140). These deposits are elastotic degeneration of the substantia propria and may represent abnormal elastic fibers. Exposure to ultraviolet light, drying, and dust can cause pinguecula formation. Occasionally, a pinguecula can become inflamed and form pingueculitis, an inflamed and vascularized lesion.

Pingueculitis is treated with a short course of topical steroids. Almost all noninflamed pinguecula can be observed without the need for surgery. If they enlarge and become a cosmetic problem, local excision easily removes the pathology. Pinguecula recurrences are slow and uncommon.

White Limbal Girdle of Vogt

The common type II limbal girdle of Vogt is an opacity occurring more often at the nasal limbus than the temporal limbus. It is a limbal degeneration directly related to aging that is found in almost everyone older than 80 years of age. Seen in 55% of patients 40 to 60 years of age, this can be considered a normal finding, although it may look like the


beginning of band keratopathy. There are subepithelial deposits of hyaline degeneration and elastosis similar to pinguecula. These are seen in an arc-like configuration peripheral to where Bowman's membrane ends (Fig. 1.141). The very thin, small, finger-like extensions found centrally do not progress.

Figure 1.140. The pinguecula is an area of elastotic degeneration appearing in the conjunctiva at the limbus but not on the cornea. Most pingueculae remain in place and do not cross the limbus to the cornea. Almost all patients older than 80 years of age have some pinguecula formation.

Because there are no symptoms and the degeneration does not progress, no treatment is necessary. It should not be confused with band keratopathy.

Spheroidal Degeneration

Spheroidal degeneration has had various names. It has been called climatic droplet keratopathy, Labrador keratopathy, keratinoid degeneration, and chronic actinic keratopathy. It is a nonhereditary degeneration that is usually related to climatic conditions but referred to as spheroidal degeneration because of the spherical appearance of the yellowish droplets.

The yellowish droplets typify this form of degeneration. They may start in the conjunctiva, at the limbus, or in the cornea. Clusters of fine to coarse yellowish droplets or larger, oval deposits are seen beneath the epithelium. They may be associated with corneal opacities and sometimes with blood vessels. They may take on a band-shaped appearance in more advanced cases (Fig. 1.142), but usually only the exposed area of the interpalpebral fissure is involved.

There are several forms. One form is associated with previous corneal disease and trauma, and another is a degenerative aging change that is usually seen nasally and later temporally. It occurs in different geographic regions and with increasing frequency with age. The degeneration is more prevalent in the northern regions (hence, the name Labrador keratopathy). The cause is unknown, but it is associated with corneal drying and exposure to the sun, wind, sand, ice, and ultraviolet light. The droplets are proteinaceous material in the anterior stroma and Bowman's layer, and they are extracellular.

Figure 1.141. The limbal girdle of Vogt consists of fine radial white lines at the temporal or nasal limbus and represents elastotic and hyaline changes. Most patients older than 60 years of age have some form of limbal girdle, and almost all patients who are very elderly have some limbal girdle of Vogt. This is a normal finding, and it does not grow farther onto the cornea as does band keratopathy.

Figure 1.142. Spheroidal degeneration. Notice the golden yellow appearance of the degenerative area in a patient with chronic corneal disease.

In most cases, the lesions are asymptomatic and need only to be observed. Where there is central corneal pathology, superficial keratectomy permanently cures the condition. Most of the time, the pathology is located nasally and temporally, and observation alone is indicated.

Coats' Ring

Coats' ring is an oval deposit of iron that is a small remnant of a previous corneal injury, as from a foreign body. Coats' ring is usually located in the region of Bowman's layer and consists of discrete white dots, located for the most part in the inferior cornea where the trauma has occurred. The white dots consist of iron deposits and are probably remnants of the previous injury.

Observation alone is indicated, because the ring does not extend superficially or deep into the cornea. It is an interesting and unusual finding (Fig. 1.143).

Figure 1.143. Coats' ring represents remnants of a foreign body. The remnants are fine iron deposits in the cornea. This benign condition need not be treated.


Salzmann's Degeneration

Salzmann's degeneration is a noninflammatory, degenerative process appearing in the superficial cornea, usually in the midperiphery. If it occurs in the visual axis, it can cause blurred vision. This was described by Salzmann as a dystrophy, but it is a degenerative change that usually occurs years after some inflammatory condition of the cornea.

Superficial, elevated, grayish opacities replace Bowman's membrane. They are elevated and do not invade the stroma. They may appear in the periphery as single or multiple opacities, or they may spread to the central cornea (Fig. 1.144). There is usually a clear area before the limbus. They are usually unilateral but can be seen in both eyes, appear in all ages, and overlie normal-appearing stroma. Iron lines may be seen around the lesion base, and there is no further extension of these degenerative changes.

When the degenerative Salzmann's changes are in the midperiphery and do not involve the visual axis, no treatment is necessary. For the central appearance of these gray mounds that interfere with vision, superficial keratectomy is indicated.

Band Keratopathy

Deposits of calcium in the cornea in a broad band-like distribution across the middle third of the cornea as a secondary deposition or associated with systemic disorders characterize the degeneration known as band keratopathy.

Band keratopathy may start as areas of light gray opacity adjacent to the limbus nasally and temporally, typically with clear small holes within the opacity. With time, which may be years, the opacities can extend centrally and meet, leading to a band of grayish haze across the cornea (Fig. 1.145). There is an accumulation of hydroxyapatite deposits or calcium carbonate, which accumulate in the epithelium, Bowman's membrane, and superficial stroma.

Figure 1.144. Salzmann's nodular degeneration. Notice the grayish individual opacities, which sometimes are linked. When these are in the visual axis, they interfere with vision, and the raised abnormalities can cause significant visual distortion. Superficial keratectomy is the treatment of choice when the opacities are in the visual axis.

Figure 1.145. Band keratopathy. The grayish deposits of calcium in a band-like distribution across the middle one third of the cornea are typical of this disease. These deposits occur secondary to a number of systemic problems and in cases of chronic corneal inflammation and anterior uveitis.

Many systemic conditions that feature hypercalcemia can cause band keratopathy. These include sarcoidosis, vitamin D toxicity, Still's disease, and Fanconi's syndrome. Band keratopathy is also seen secondary to chronic inflammation of the cornea and in cases of anterior uveitis. It may occur secondary to drug toxicity. In the past, the preservative in a commercial pilocarpine preparation was the cause of band keratopathy.

Early cases of band keratopathy, when the calcific degeneration is at the nasal and temporal limbus, do not have to be treated. The deposits of calcium usually are in the region of Bowman's membrane, and the corneal surface is not disturbed. As the deposits move centrally and involve more of the epithelium, there may be irregular astigmatism from the marked surface irregularity. For patients with discomfort from calcific deposits or blurred vision because the calcium deposit is central, the calcium may be removed by using EDTA, a chelating agent. In more severe cases, superficial keratectomy is necessary. Most cases of band keratopathy do not have to be treated.

Complications of Corneal Surgery

Whorl Keratopathy After Penetrating Keratoplasty

After keratoplasty, some patients may develop a whorl or hurricane vortex of epithelial staining in the newly reepithelialized corneal button. Whorl keratopathy stains with fluorescein or rose bengal and represents a pattern of reepithelialization, with the epithelium growing in from the periphery in a hurricane or whorl-like centripetal pattern (Fig. 1.146). In the more severe cases, this can cause corneal epithelial disturbance and blurred vision. It is more marked after keratoplasty in patients who are sensitive to preservatives in some topical medications. This usually disappears


with time, leaving the corneal epithelium normal and without opacification.

Figure 1.146. Whorl keratopathy in a patient who had a corneal transplant. Notice the hurricane-like appearance of this defect, which diffusely stains with fluorescein.

When whorl keratopathy appears in the first week or two after keratoplasty, reducing or eliminating topical medications that contain preservatives can diminish the whorl keratopathy. Artificial tears without preservatives and lubricating ointment at bedtime are helpful. As the condition gradually fades, the corneal epithelium may become opacified in a whorl-like distribution, and epithelial debridement is needed to allow healthy epithelium to grow back in its place. This problem usually does not jeopardize corneal graft clarity.

Subepithelial Corneal Infiltrates in Corneal Graft Rejection

This mild form of graft rejection was described by Krachmer about 15 years ago, and is similar to the subepithelial infiltrates in adenovirus infection. The subepithelial infiltrates appear several weeks to many years after corneal transplantation.

Corneal graft rejection occurs in as many as 25% of corneal transplants. Epithelial or endothelial rejection has been the classic form of corneal transplant rejection. Subepithelial corneal infiltrates may appear weeks or years after transplantation and are also a sign of active graft rejection (Fig. 1.147). They are inflammatory infiltrates beneath Bowman's membrane in the superficial stroma and have the exact appearance of subepithelial infiltrates in adenovirus infection. There is no virus infection of the graft, and these subepithelial infiltrates represent a newly recognized form of graft rejection. They may be associated with epithelial rejection and with endothelial rejection.

Corneal transplants must be observed at each office visit for signs of subepithelial infiltrates. If even one infiltrate appears where there had been none previously, treatment with topical steroids usually is all that is necessary to resolve the infiltrates. The topical steroids should be used more frequently at first QID and then tapered over several weeks to months. These infiltrates may be recurrent.

Figure 1.147. Subepithelial corneal deposits in the early stage of corneal graft rejection. These deposits are exactly the same as those seen in adenovirus infection, but there is no virus infection in this condition. These deposits can occur individually or grouped, as seen here. They must be treated with topical steroids to prevent more severe forms of rejection.

Endothelial Graft Rejection of Corneal Transplants

Endothelial graft rejection is a serious graft rejection that is first seen as a wavy endothelial line, usually starting at the periphery and going across the back of the new corneal transplant. Epithelial rejection is more common but less serious.

Endothelial graft rejection has been known for many years. Khoudadoust described the linear pattern of the endothelial rejection line that bears his name (Fig. 1.148). This pattern represents a line of sensitized lymphocytes that progresses across the back of the cornea from the host recipient graft edge centrally, until it reaches the other side of the cornea. As this line progresses, new donor endothelial cells are destroyed, but all cells are not destroyed. This line may


progress across the cornea, leaving enough viable endothelial cells to maintain graft clarity. In more severe cases of endothelial rejection, corneal stromal edema occurs if enough endothelial cells are damaged as the line progresses.

Figure 1.148. Endothelial graft rejection with Khoudadoust's line, which is a line of lymphocytes advancing across the back of the cornea. Note also the keratic precipitates.

The use of frequent topical steroids, such as 1% prednisolone, hourly for a few days and then tapering to every 2 hours, every 3 hours, and further is the treatment of choice. Based on the response of the endothelial rejection line, the treatment is slowly tapered but maintained over a considerable period of time (months to years). If there has been previous rejection or if this is a second graft, some physicians treat endothelial graft rejection with oral or even intravenous cortisone, and in some cases, cyclosporine. Most ophthalmologists treat endothelial rejection with high-frequency topical applications of 1% prednisolone alone.

Complications of Refractive Surgery

Infection in Radial Keratotomy

Infection occurring in the radial keratotomy incisions is an uncommon event. Any appearance of stromal inflammation in one of the radial keratotomy incisions should be treated as a potential corneal infection to prevent spread of the disease and possible endophthalmitis. Recognition of infection in the radial keratotomy incisions should be simple, because the eye is inflamed, and an infiltrate is seen somewhere along the line of the incision (Fig. 1.149).

Treatment of these potential infections requires the frequent application of topical antibiotics in the early phase. Fortified medications to cover gram-positive and gram-negative organisms should be used, or broad-spectrum antibiotics, such as fluoroquinolone drops, should be frequently applied.

Perforation of the Cornea in Radial Keratotomy

Any perforation of the cornea during a radial keratotomy procedure is a potential problem. Microperforations initially were seen in 5% to 10% of cases, but macroperforations were much less common. As the radial keratotomy incision is being made, loss of aqueous in the incision indicates perforation of the cornea. If there is only a bead or small drop of aqueous, many physicians continue the procedure but decrease the blade depth. If there is more than just a bead of aqueous, a macroperforation has occurred.

Figure 1.149. Radial keratotomy with bacterial infection in the 3-o'clock incision.

Figure 1.150. Radial keratotomy, showing two sutures in the 8-o'clock incision resulting from a macroperforation.

Microperforations do not require suturing, but a macroperforation with significant softening of the eye requires suturing of the incision and delaying finishing the procedure (Fig. 1.150).

Corneal Haze in Excimer Laser Photorefractive Keratectomy Surgery

Excimer laser photorefractive keratectomy surgery for low degrees of myopia causes little haze of the cornea. For higher amounts of myopia, there may be significant haze that can interfere with vision.

Corneal haze, which occurs after excimer laser photorefractive surgery and phototherapeutic surgery, is located in the superficial stroma and the region of Bowman's membrane. This haze, which occurs fairly frequently for patients with high degrees of myopia, can take many months to 1 year to heal, and in some patients with high degrees of myopia, the haze can be permanent (Fig. 1.151). Fortunately, the haze does not interfere significantly with vision in its milder form, and only when the haze is more apparent is there some visual distortion.

Topical steroids can decrease the haze and even eliminate it, but with use of topical steroids for long periods of time after excimer laser phototherapeutic and photorefractive surgery, there is the risk of lens opacity and glaucoma in steroid responders.

LASIK Complications

Laser in situ keratomileusis (LASIK) is a refractive surgery procedure that involves pressurizing the globe and using a


microkeratome to create a thin corneal flap. A small hinge is left at one edge of the flap to assist in replacing the flap. The flap is lifted and the excimer laser is used to reshape the underlying corneal stroma, after which the flap is replaced and allowed to adhere without sutures. The great majority of the time, the flap fashioned during the LASIK procedure is of perfect quality. It should be well centered, of uniform thickness, without significant epithelial defects and have an adequate hinge.

Figure 1.151. A superficial haze in the cornea occurred 6 months after excimer laser photorefractive surgery. It was considered a 2+ haze, which produced mild interference with vision.

LASIK Button-hole

Occasionally LASIK flaps are not perfect. Slight decentrations or small epithelial defects are of minimal consequence. If a free cap occurs, due to amputation of the hinge, the excimer laser treatment can proceed if the cap is large enough to cover the entire ablation area. If the cap is too small or the flap is not of uniform thickness, the laser treatment should be aborted. Additionally, if the hinge is so large or the flap so decentered that it impinges on a significant portion of the ablation area, the laser treatment should also be aborted. In these cases, the flap or free cap should be placed back in its original position and allowed to heal. Often a bandage soft contact lens aids in stabilizing the flap. After the flap is allowed to heal for at least 3 to 6 months, a repeat LASIK procedure can often be performed by recutting a new, ideally thicker, flap, usually with excellent results. It is possible, however, for the original poor flap to loosen or detach during the second procedure, causing another thin or shredded flap.

A thin, poor quality flap can occur if there is inadequate intraocular pressure elevation during flap creation (Fig. 1.152). A button-hole in the flap may be due to low intraocular pressure, but may also be related to an excessively steep cornea that dimples inward when the microkeratome runs across the surface. Corneas with keratometry readings greater than 48 to 49 diopters are at higher risk for button-holes. Corneas with small corneal diameters, for example, less than 11.5 mm, are also at higher risk for button-holes.

Figure 1.152. Epithelial irregularities can be seen paracentrally from the 12- to 1-o'clock and 8- to 9-o'clock positions on postoperative day 1 after a thin irregular laser in situ keratomileusis flap was created secondary to loss of suction during the microkeratome pass. The flap pieces were replaced and bandage soft contact lens used. The vision returned to preoperative levels within a few days.

LASIK Free Cap

Creation of an excellent flap during the LASIK procedure is critical to obtain a superb refractive result. A free cap occurs when the hinge is amputated by the microkeratome pass (Fig. 1.153). This typically occurs in flat corneas, generally with keratometry readings less than 40 to 41 diopters. Large corneas, usually greater than 14.5 mm in horizontal diameter, are also prone to free caps.

If a free cap occurs, it needs to be recognized immediately so it is not lost. It should be carefully removed from the microkeratome head and placed in an antidesiccation chamber with the epithelial side down on a drop of saline. If the area under the free cap is large enough to allow the excimer laser ablation, then the surgeon may proceed with the laser treatment.


Whether the laser treatment is performed or not, the cap should be replaced in its original position. It is critical that the epithelial side is up. The preplaced ink marks are used to ensure the cap is right side up and in its natural orientation. A bandage soft contact lens may be used to prevent cap movement.

Figure 1.153. A small free cap was created during laser in situ keratomileusis. It was replaced without laser ablation. The central edge of the free cap is elevated, causing irregular astigmatism and poor vision.

LASIK Flap Dislocation

During a LASIK procedure, after the flap is resituated in its original position, it is allowed to adhere for several minutes. The eyelid speculum is removed, using care not to touch the flap. The flap is checked at the slit lamp a short time later to ensure good positioning. It is critical that the patient not rub the eye or touch the flap for several days, as the flap can easily dislodge.

Flap dislocations range from mild (Fig. 1.154) to severe (Fig. 1.155). In general, they must be repositioned using an operating microscope. The stromal bed and underside of the flap need to be cleaned of foreign debris and epithelium before the flap is replaced in its original position. An attempt is made to iron out any visible striae. A bandage soft contact lens may be helpful in aiding reepithelialization and securing the flap. If the flap fails to adhere properly to the stromal bed, sutures may be required to secure the flap in position.

LASIK Infection

Infection after LASIK is a rare, but potentially devastating, condition. While sterilized instruments and pre- and postoperative antibiotics are used routinely for LASIK, infection can still occur. Infection can occur in the superficial cornea, at the edge of the flap, or in the flap interface. Mild superficial infections can be treated with topical antibiotics. More severe infections require scrapings for smears and cultures and intensive topical antibiotic use. Infections located in the flap interface often require lifting of the flap and obtaining cultures from the interface. At the same time, the stromal bed should be irrigated with antibiotics. Although the usual organisms causing infectious keratitis are often found, there is a higher incidence of unusual organisms, such as atypical mycobacteria (Fig. 1.156).

Figure 1.154. The flap is slightly dislodged on postoperative day 1. It was associated with macrostriae and decreased vision. An epithelial defect is apparent at the flap edge from the 9- to 12-o'clock positions, where there was significant edge misalignment. It was repositioned under the operating microscope with excellent return of vision.

Figure 1.155. This flap became totally dislodged 3 months after laser in situ keratomileusis due to being poked in the eye with a stick. The flap is still attached to the cornea at its hinge nasally. It was repositioned under an operating microscope and healed without difficulty.

LASIK Diffuse Lamellar Keratitis

Diffuse lamellar keratitis (DLK) is a condition of inflammation in the LASIK interface that begins within a few days after surgery. It has also been termed Sands of the Sahara syndrome,


among other names. Patients notice increased irritation, light sensitivity, glare, and decreased vision within a few days after LASIK. On slit lamp examination, there is little if any conjunctival injection. There is a granular haze in the flap interface, which can be peripheral or central. It may have a desert sand appearance (Fig. 1.157A, B). In more severe cases the vision is dramatically affected. The interface opacity can become quite dense, especially centrally. It is differentiated from a bacterial infection by minimal pain, conjunctival injection, and anterior chamber reaction.

Figure 1.156. Five weeks after laser in situ keratomileusis, this flap interface infection has not responded to multiple medical treatments, causing the flap to melt. The flap was surgically amputated to allow better antibiotic penetration to the stroma. The cultures ultimately revealed atypical mycobacteria. The infection eventually responded to additional medical treatment, but the patient was left with a significant corneal scar.

Figure 1.157. A: This eye developed diffuse lamellar keratitis several days after uncomplicated laser in situ keratomileusis. Note the desert sand appearance centrally. B: In this slit beam view of diffuse lamellar keratitis, the peripheral extent of the granular inflammatory response can be seen. (Courtesy of Irving M. Raber, M.D.)

The etiology of DLK is most likely multifactorial. It can occur sporadically or in clusters. When DLK has occurred in clusters, there is good evidence that it may be related to bacterial toxins remaining on the instruments and equipment after heat sterilization. It may also be related to lubricating oils from the microkeratome equipment, meibomian secretions, or other inflammatory substances in the flap interface.

The treatment regimen depends on the severity of the inflammation. Mild cases, where the vision is not affected, can be followed closely to monitor for worsening. More severe cases should be treated with intensive topical steroids, such as every 1 to 2 hours, and followed closely. In the most severe cases there is a dense central inflammatory reaction that can lead to stromal necrosis and significant corneal scarring, thinning, and flattening. In such cases, lifting of the flap and irrigation of the inflammatory debris (in addition to intensive topical steroids) may help prevent excessive tissue damage. If an infection cannot be ruled out, the flap should be lifted and scrapings taken for smears and cultures, and treatment with antibiotics should be initiated.

LASIK Epithelial Ingrowth

Corneal surface epithelial cells can grow under a LASIK flap. Epithelial ingrowth typically occurs when an epithelial defect along the flap edge does not heal properly, allowing a sheet of epithelium to grow under the flap. The epithelium cannot generally be seen until several weeks after surgery, when it looks like a gray-white layer in the flap interface (Fig. 1.158). It often has tongues of epithelial growth and may have a speckled or putty-like pattern (Fig. 1.159). Small islands of epithelial cell growth at the edge of LASIK flaps are common and of minimal concern. When a large sheet of epithelium grows under a flap, it can cause elevation of the flap and irregular astigmatism. Additionally, since it is difficult for nutrients to get from the deep cornea through the sheet of epithelium, and perhaps due to epithelial collagenases, the flap over the epithelial ingrowth can undergo necrosis. Risk factors for epithelial ingrowth include epithelial basement membrane dystrophy, a history of recurrent erosions, advanced age, LASIK enhancement, and flap dislodgment.

Figure 1.158. This dense gray-white plaque of epithelial ingrowth caused punctate staining of the overlying flap along with central irregular astigmatism and decreased vision. It required removal under an operating microscope.

Figure 1.159. This putty-like epithelial ingrowth was not causing problems with the health of the flap, but was inducing mild irregular astigmatism and slightly decreased vision.


Treatment depends on the extent and severity of the epithelial ingrowth. Mild, peripheral ingrowth measuring less than 1 to 2 mm can be followed. Ingrowth greater than 2 mm, especially if it is thick, requires close follow-up, every 1 to 2 weeks initially, to make sure it doesn't progress or cause damage to the flap. If there is any evidence of flap necrosis or if the ingrowth is causing decreased vision from flap distortion, it should be removed. Removal requires lifting the flap and scraping both the stromal bed and the undersurface of the flap to remove all epithelial cells. The flap is replaced and the epithelial tags at the flap edge are realigned as much as possible to prevent recurrence of the ingrowth.

LASIK Flap Striae

Striae, or folds, in LASIK flaps are often seen. Microstriae are common and may result from slight folding in the flaps that are being replaced over a stromal bed that is slightly smaller than the flap because it has been ablated by the laser (Fig. 1.160). Microstriae do not affect the vision. Macrostriae, or corneal folds, occur when the LASIK flap is not perfectly aligned (Fig. 1.161). They can affect the vision, especially if they are located centrally, and should generally be ironed out.

Figure 1.160. These microstriae are commonly seen after laser in situ keratomileusis and do not affect vision. They probably result from slight folding of the flap, which is being placed into a bed that is slightly smaller due to the laser ablation.

Figure 1.161. These macrostriae or folds near the flap hinge nasally resulted from a slightly dislodged flap on postoperative day 1 and were associated with decreased vision. The flap was replaced and the vision improved. The striae diminished greatly, but did not completely disappear.

LASIK Iron Line

After LASIK for myopia, the central corneal curvature is flatter than before surgery. The tear film distribution is therefore altered, allowing some pooling centrally. This pooling can cause iron deposition in the central epithelium (Fig. 1.162). A similar effect can be seen after steeping of the cornea from treatment of hyperopia. In the case of hyperopia, a pseudo-Fleischer's ring iron deposition can be seen. These iron lines do not affect vision.

Figure 1.162. A small, slightly stellate iron line can be seen centrally in this eye 1 year after myopic laser in situ keratomileusis. It does not affect vision.

Figure 1.163. A tiny fiber fragment is seen in the laser in situ keratomileusis flap interface 5 weeks after surgery. A mild fibrotic reaction around the piece of debris can be seen. Small degrees of interface debris are common and generally do not affect vision.


LASIK Interface Debris

After the flap is replaced during the LASIK procedure, the interface is irrigated with saline to remove debris. The flap is inspected under the operating microscope after irrigation and again at the slit lamp a short time after the procedure. Ideally, minimal to no debris remains in the interface. A small amount of debris is of no consequence. There may be a mild fibrotic reaction around the debris for several weeks to months after surgery (Fig. 1.163). A large amount of debris, especially if it is centrally located, should be removed at the time of surgery. In that case, the flap is refloated, the interface reirrigated, and the flap allowed to readhere.


Limbal Dermoid

A limbal dermoid is a smooth, solid, round mass of tissue containing entities such as hair follicles and fatty deposits. Dermoids are associated with Goldenhar's syndrome, a nonhereditary condition that also includes ear abnormalities such as preauricular skin tags and vertebral abnormalities.

Figure 1.164. A: This classic limbal dermoid is smooth, round, white, and in an inferotemporal location. B: Central corneal dermoids are much less common and are part of the differential diagnosis of congenital cloudy corneas.

Dermoids can vary in shape and location, but classically, they are white, circular lesions that are several mm in diameter and are elevated (Fig. 1.164A). They typically occur at the inferotemporal limbus and involve the sclera and cornea, but they may occur elsewhere, including centrally (Fig. 1.164B). There may be hairs protruding from the surface of the dermoid.

Dermoids can be visually and cosmetically significant. They may be removed by lamellar keratectomy, lamellar keratoplasty, or penetrating keratoplasty. When lamellar surgery is contemplated, full-thickness corneal tissue should be available, because dermoids can involve the full thickness of the cornea. Depending on the size, shape, and location, surgical removal may or may not improve the visual acuity and cosmetic appearance. Lipodermoids are dermoids with a significant lipid component, and consequently, they are more yellow in appearance. They also tend to be more superiorly and posteriorly located than limbal dermoids.

Pyogenic Granuloma

A pyogenic granuloma is a mass of exuberant granulation tissue that develops on the conjunctiva or skin. These can occur secondary to trauma, surgery, a chalazion or hordeolum, a chemical burn, or any necrotizing process. A deep red, highly vascularized, often pedunculated mass arises from the conjunctiva or skin (Fig. 1.165). There may be an associated mucopurulent discharge.

Small, pyogenic granulomas can resolve spontaneously over several weeks. Topical steroids or antibiotic-steroid combinations can also be used to treat pyogenic granulomas. Occasionally, they can require surgical excision.

Conjunctival Intraepithelial Neoplasia

Conjunctival intraepithelial neoplasia is a term used to designate benign and malignant in situ lesions. The clinical and histopathologic differentiation between these lesions is difficult.


Conjunctival intraepithelial neoplasia has a typical clinical appearance characterized by a papillomatous lesion beginning at the limbus and extending onto the conjunctiva and cornea (Fig. 1.166A). The presence of vascular fronds in the limbal and conjunctival components is an indication for a wide excisional biopsy for diagnosis and therapy. The corneal component is gray, nonstaining, and slightly raised, with a well-defined geographic or whorl-like border. The conjunctival lesion can also have a gelatinous appearance (Fig. 1.166B). Squamous cell dysplasia and carcinoma in situ have similar clinical appearances but differ histopathologically by the extent of replacement of the conjunctival epithelium with abnormal cells (Fig. 1.166C).

Figure 1.165. A large, pedunculated, pyogenic granuloma arising from the conjunctival surface of the upper eyelid is apparent in the area of an old chalazion.

Figure 1.166. A: This conjunctival mass with typical vascular fronds and a gray extension onto the cornea was determined to be squamous cell carcinoma in situ by histopathologic analysis. B: This gelatinous conjunctival lesion involving the limbus and extending near the caruncle was also a squamous cell carcinoma in situ. C: Pathology of this lesion demonstrates the characteristic abrupt transition from normal to diseased conjunctiva. (Courtesy of Ralph C. Eagle, Jr, M.D., Department of Pathology, Wills Eye Hospital.)

Treatment consists of wide excisional biopsy, cryotherapy of the conjunctival margin, and application of absolute alcohol to the area of corneal involvement in some cases. The prognosis is good. Lesions can recur locally if the margins of excisions are not free of tumor. Invasive disease is uncommon and frequently associated with neglect or immunocompromised hosts.

Malignant Melanoma of the Conjunctiva and Cornea

Malignant melanoma of the conjunctiva can arise from three sources. It can be seen after the development of a primary acquired melanosis, develop from preexisting nevi, or arise de novo. Approximately 75% of cases of conjunctival melanoma arise from primary acquired melanosis.

Malignant melanoma of the conjunctiva occurs equally in men and women, usually in their fifties. It is most often seen in Caucasians, and rarely in persons of African descent.

The clinical manifestations are quite variable, and in many cases, malignant melanoma does not take on any typical appearance (Fig. 1.167A). Melanomas at the limbus


usually do not arise from preexisting conjunctival nevi (Fig. 1.167B). Corneal malignant melanomas are rare, with most of these lesions extending from the conjunctival limbus onto the cornea. Increased vascularity and nodular thickening with fixation to underlying tissue may indicate change from primary acquired melanosis to malignant melanoma.

Figure 1.167. A: A malignant melanoma of the limbus and cornea had been incompletely excised and recurred. B: A conjunctival nevus.

Complete surgical excision is the ideal treatment of conjunctival, limbal, and corneal malignant melanomas. Because it is difficult to be certain that all of the lesions have been removed on the conjunctival side, cryotherapy should be applied to the surrounding conjunctiva and the lesion base. The recurrence rate for conjunctival melanoma is approximately 25%.

Lymphomatous Infiltration

The conjunctiva may be involved by several benign and malignant lymphoid infiltrative processes, including hyperplasia, lymphoma, pseudotumor, and leukemia.

The typical lymphomatous lesion involving the conjunctiva presents as a salmon-colored, soft, fleshy elevation without an inflammatory reaction (Fig. 1.168). Benign and malignant lesions are often difficult to differentiate clinically. Biopsy with a histopathologic examination of the specimen and fresh tissue for immunologic marker studies are helpful in making the diagnosis.

Figure 1.168. A: A 45-year-old woman presented with a salmon-colored soft tissue swelling of the inferior bulbar conjunctiva. B: Biopsy revealed a monomorphous sheet of atypical lymphocytes. Flow cytometric studies disclosed a monoclonal population of B cells consistent with lymphoma. (Hematoxylin & eosin stain; original magnification 100.)

Patients with conjunctival lymphoma should have a thorough systemic workup and evaluation by a specialist skilled in this area. Only 10% of these patients have preexisting systemic lymphoma. Local lesions can be excised, and more diffuse lesions can be treated with irradiation. Systemic lymphoma requires treatment and follow-up by an oncologist.


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Wills Eye Hospital Atlas of Clinical Ophthalmology
The Wills Eye Hospital Atlas of Clinical Ophthalmology
ISBN: 078172774X
EAN: 2147483647
Year: 2001
Pages: 17

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