3 - Preoperative Evaluation Perioperative Management | Current Medical Diagnosis & Treatment, 2006 (Current Medical Diagnosis and Treatment)

Eye

Paul Riordan-Eva FRCS, FRCOphth

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SYMPTOMS OF OCULAR DISEASE

Redness

Redness is the most frequently encountered symptom of ocular disorders. It is due to hyperemia of the conjunctival, episcleral, or ciliary vessels; erythema of the eyelids; or subconjunctival hemorrhage. The major differential diagnoses are conjunctivitis, corneal disorders, acute glaucoma, and acute uveitis (Table 7-1).

Vafidis G: When is red eye not just conjunctivitis? Practitioner 2002;246:469.

Ocular Discomfort

Ocular pain may be caused by trauma, infection, inflammation, or sudden increase in intraocular pressure.

Foreign body sensation may be due to corneal or conjunctival foreign bodies, disturbance of the corneal epithelium, or rubbing of eyelashes against the cornea (trichiasis).

Photophobia is usually due to corneal inflammation (keratitis) or iritis. Other causes are albinism, aniridia, cone dystrophy, aphakia, or fever associated with various systemic infections.

Itching is characteristically associated with allergic eye disease.

Scratching and burning due to dryness of the eyes may be due to dry environment, ocular surface disease, systemic disorders (eg, Sj gren's disease), or drugs (eg, atropine-like agents).

Watering is usually due to inadequate tear drainage through obstruction of the lacrimal drainage system or malposition of the lower lid. Reflex tearing occurs with any disturbance of the corneal epithelium.

“Eyestrain” & Headache

Eyestrain is discomfort associated with prolonged reading or close work. Refractive error including presbyopia, inadequate illumination, and latent ocular deviation are the usual causes. Headache is rarely due to ocular disorders but is a major symptom of giant cell arteritis, an important cause of visual loss in older individuals.

Conjunctival Discharge

Purulent discharge usually indicates bacterial infection of the conjunctiva, cornea, or lacrimal sac. Viral conjunctivitis or keratitis produces watery discharge; allergic conjunctivitis results in tearing, ropy discharge, and itching.

Visual Loss

Causes of blurred vision include refractive error, cataract, macular degeneration, diabetic retinopathy, vitreous hemorrhage, retinal detachment involving the macula, central retinal vein occlusion, central retinal artery occlusion, intraocular inflammation (uveitis), corneal opacities, and optic nerve disorders.

Monocular field loss usually indicates disease of the retina or optic nerve. Important causes are chronic glaucoma, retinal detachment, branch retinal artery or vein occlusion, optic neuritis, and anterior ischemic optic neuropathy, all of which, especially chronic glaucoma, may be bilateral. Lesions of the optic chiasm due to pituitary tumors usually result in bitemporal field loss. Retrochiasmal lesions cause contralateral homonymous field defects. The more posterior the lesion in the visual pathway, the more similar are the defects in the two eyes. Cerebrovascular disease and tumors are responsible for most lesions of the retrochiasmal visual pathways.

Visual Impairment & Blindness

An individual is visually impaired if best corrected distant visual acuity in the better eye is 20/80 or less or if visual fields are significantly restricted. Legal blindness is defined as visual acuity for distant vision of 20/200 or less in the better eye with best correction or widest diameter of the visual field subtending an angle of less than 20. Most states require best corrected visual acuity with both eyes of 20/40 for an unrestricted driving license.

The World Health Organization (WHO) estimates that of the world's population over 160 million people are visually impaired and about 37 million are blind. The most frequent causes of blindness worldwide are cataract, glaucoma, age-related macular degeneration, and diabetic retinopathy, all of which are increasing in prevalence, especially in older individuals, as well as

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trachoma. In the United States, over 3 million adults aged 40 years or over are blind or visually impaired.

Table 7-1. The inflamed eye: Differential diagnosis of common causes.

	Acute Conjunctivitis	Acute Uveitis	Acute Glaucoma¹	Corneal Trauma or Infection
Incidence	Extremely common	Common	Uncommon	Common
Discharge	Moderate to copious	None	None	Watery or purulent
Vision	No effect on vision	Often blurred	Markedly blurred	Usually blurred
Pain	Mild	Moderate	Severe	Moderate to severe
Conjunctival injection	Diffuse; more toward fornices	Mainly circumcorneal	Mainly circumcorneal	Mainly circumcorneal
Cornea	Clear	Usually clear	Steamy	Clarity change related to cause
Pupil size	Normal	Small	Moderately dilated and fixed	Normal
Pupillary light response	Normal	Poor	None	Normal
Intraocular pressure	Normal	Commonly low but may be elevated	Elevated	Normal
Smear	Causative organisms	No organisms	No organisms	Organisms found only in corneal ulcers due to infection
¹Angle-closure glaucoma.

Evans JR et al: Causes of visual impairment in people aged 75 years and older in Britain: an add-on study to the MRC Trial of Assessment and Management of Older People in the Community. Br J Ophthalmol 2004;88:365.

Friedman DS et al: Racial variations in causes of vision loss in nursing homes: The Salisbury Eye Evaluation in Nursing Home Groups (SEEING) Study. Arch Ophthalmol 2004;122:1019.

Resnikoff S et al: Global data on visual impairment in the year 2002. Bull World Health Organ 2004;82:844.

Diplopia

Double vision typically results from acquired ocular misalignment. This may be caused by central disorders of eye movements or cranial nerve palsies due to head injury, vascular, neoplastic, or inflammatory intracranial disease, or Wernicke's syndrome; myasthenia gravis; or intraorbital lesions including Graves' ophthalmopathy and muscle entrapment as a result of orbital blowout fracture. Monocular diplopia, which persists when the fellow eye is covered, is usually due to refractive error or lens opacities.

“Spots Before the Eyes” & “Flashing Lights”

Spots before the eyes (floaters) are often caused by benign vitreous opacities. However, they may also be caused by posterior vitreous detachment, vitreous hemorrhage, or posterior uveitis. Sudden onset of floaters, particularly when associated with flashing lights (photopsia), necessitates dilated fundal examination to exclude a retinal tear or detachment.

Polkinghorne PJ et al: Analysis of symptoms associated with rhegmatogenous retinal detachments. Clin Exp Ophthalmol 2004;32:603.

OCULAR EXAMINATION

Abbreviations and symbols commonly used in ophthalmology are listed in the accompanying box.

Visual Acuity (VA)

Corrected distant visual acuity should be tested for each eye in turn, using a Snellen or logMAR (EDTRS) chart, annotated according to the distance at which each line can be read by a normal individual. It is traditionally measured at 20 feet (6 meters in Europe) or nearer if vision is poor, but other test distances may be used. Visual acuity is expressed as a fraction—the test distance over the figure assigned to the lowest line the patient can read. If the patient is unable to read the top line of the chart, acuity is recorded as counting fingers (CF), hand movements (HM), perception of light (LP), or no light perception (NLP). A corrected acuity of less than 20/30 (6/9) is abnormal.

Near acuity is tested with a reduced Snellen chart or standardized reading test types. The patient must be wearing appropriate reading correction.

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Visual Fields

Confrontation testing, preferably using a 5-mm red target, is valuable for rapid assessment of field defects. Amsler charts are the easiest method of detecting central field abnormalities due to macular disease.

Corbett JJ: The bedside and office neuro-ophthalmology examination. Semin Neurol 2003;23:63.

Pupils

The pupils are examined for absolute and relative size and reactions to both light and accommodation. A large, poorly reacting pupil may be due to third nerve palsy, iris damage caused by acute glaucoma, or pharmacologic mydriasis. A small, poorly reacting pupil is observed in Horner's syndrome, inflammatory adhesions between iris and lens (posterior synechiae), or neurosyphilis (Argyll Robertson pupils). Physiologic anisocoria is a common cause of unequal pupils that react normally.

A relative afferent pupillary defect, in which the pupillary light reaction is reduced when light is shined into the affected eye compared with the normal eye, generally indicates optic nerve disease. It is detected with the “swinging light test,” in which the pupillary light reactions are compared as a bright light is moved from one eye to the other.

Extraocular Movements

Examination of extraocular movements begins with an assessment of whether the two eyes are correctly aligned. A misalignment of the visual axes under binocular viewing conditions is known as a manifest deviation, or tropia. A deviation when binocular function is disrupted is known as a latent deviation, or phoria. A manifest deviation may be apparent by comparing the relative positions of the corneal light reflexes. A more reliable test is the cover test, in which the deviated eye moves to take up fixation when the other eye is occluded. The correctional movement is in the direction opposite to that of the original manifest deviation. If no manifest deviation is present, occlusion of one eye will elicit any latent deviation because binocular function will have been disrupted. As the occluder is removed (uncover test), latent deviation is then detected by any correctional movement that occurs to reestablish the normal alignment of the eyes. Latent deviation is common among normal individuals.

Horizontal diplopia indicates dysfunction of the medial and lateral rectus muscles; vertical diplopia results from dysfunction of the superior or inferior recti or the obliques. The false outer image arises from the affected eye. If muscle contraction is impaired, the image separation will be greatest in its normal direction of action; if a muscle cannot relax, image separation will be greatest in the direction opposite to its normal action. For example, a paretic lateral rectus or a tethered medial rectus of the right eye will cause maximal image separation on looking to the right.

ABBREVIATIONS & SYMBOLS USED IN OPHTHALMOLOGY

A or Acc

Accommodation

Ax or x

Axis of cylindric lens

BI or BO

Base-in or base-out (prism)

Counting fingers

Cyl

Cylindric lens or cylinder

Diopter (lens strength)

Esophoria

EOG

Electro-oculography

EOM

Extraocular muscles or movements

ERG

Electroretinography

Hyperphoria

Hand movements

Hypertrophia

IOP

Intraocular pressure

IPD

Interpupillary distance

J1—J20

Test types (Jaeger) for testing reading vision

Keratic precipitates

Light perceptions

L Proj

Light projection

NLP

No light perception

NPC

Near point of convergence

Hand movements

OD (R, or RE)

Oculus dexter (right eye)

OS (L, or LE)

Oculus sinister (left eye)

Oculi unitas (both eyes)

Prism diopter

Pinhole

PRRE

Pupils round, regular, and equal

S or Sph

Spherical lens

Esotropia (with L or R)

Visual acuity

VER

Visual evoked response

Exophoria

Exotropia

Plus or convex lens

Minus or concave lens

[combined with]

Combined with

∞

Infinity (6 meters [20 feet] or more distance)

Degree (measurement of strabismus angle)

Prism diopter

Nystagmus in the primary position is always abnormal. Minor degrees of nystagmus at the extremes of gaze are normal. Other forms of physiologic nystagmus include optokinetic nystagmus and nystagmus induced by rotation or caloric stimulation. Exaggerated gaze-evoked nystagmus may be due to drugs or posterior fossa disease.

Proptosis (Exophthalmos)

Proptosis is suspected when there is widening of the palpebral aperture, with exposure of sclera both superiorly

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and inferiorly. (Eyelid retraction causes more exposure superiorly than inferiorly.) By viewing from above while the patient is asked to look down and the upper lids are lifted by the examiner, a further estimate of the degree of proptosis can be made. Exophthalmometry provides objective assessment. In nonaxial proptosis, there is also horizontal or vertical displacement of the globe, indicating the presence of a mass lesion outside the extraocular muscle cone.

The most frequent cause of proptosis in adults is dysthyroid eye disease. Other causes include cellulitis, tumors, and orbital pseudotumor.

Ptosis

Ptosis is usually due to eyelid disease. Neurologic causes of ptosis include Horner's syndrome, in which the pupil is constricted, and third nerve palsy, in which there are abnormalities of eye movements and the pupil may be dilated and react poorly to light. In myasthenia gravis, the pupils are normal and characteristically the ptosis is fatiguable.

Anterior Segment Examination

Although slit-lamp examination is more sensitive, examination with a flashlight and loupe usually provides sufficient information for initial assessment. Patterns of redness indicate the site of the problem. In conjunctivitis, it extends diffusely across the globe and the inner surface of the lids. Keratitis, intraocular inflammation, and acute glaucoma lead to predominantly circumcorneal injection. Episcleritis and scleritis cause localized or diffuse deep injection, which in the case of scleritis is associated with blue discoloration.

Focal lesions of the cornea due to infection or trauma can be differentiated from the diffuse corneal haze of acute glaucoma and from the cloudiness of the anterior chamber and perhaps hypopyon (white cells within the anterior chamber) of iritis. Instillation of fluorescein and examination with a blue light aid in detection of corneal epithelial defects.

Direct Ophthalmoscopy

Direct ophthalmoscopy, ideally following pupil dilation with tropicamide 0.5–1%, which rarely induces angle-closure glaucoma, is used for examining the retina. Assessment of the red reflex and clarity of fundal details indicate the degree of media opacity. Abnormalities may then be localized to the cornea, lens, or vitreous by variations of focus of the ophthalmoscope and use of parallax.

The optic disk is examined for swelling, pallor, and glaucomatous cupping. Macular lesions causing poor central vision are usually apparent. The retinal vessels are scrutinized for caliber and wall changes. Retinal hemorrhages, exudates, and cotton-wool spots are noted. In hospital patients, dilation should be noted in the record to avoid confusion on neurologic examination.

OPHTHALMOLOGIC REFERRALS

Sudden loss of vision requires emergency ophthalmologic consultation. Important causes in an uninflamed eye are vitreous hemorrhage, retinal detachment, exudative age-related macular degeneration, retinal artery or vein occlusions, anterior ischemic optic neuropathy, giant cell arteritis, and optic neuritis. In an inflamed eye, acute anterior uveitis, acute glaucoma, and corneal ulcer are possibilities. Other emergencies include orbital cellulitis, gonococcal keratoconjunctivitis, and ocular trauma.

Patients developing gradual loss of vision should also be referred. The principal causes are cataract, atrophic age-related macular degeneration, chronic glaucoma, chronic uveitis, and intraorbital and intracranial tumors.

Patients with diabetes must undergo annual examination through dilated pupils. Any patient with myopia should be warned of the increased risk of retinal detachment and made aware of the importance of reporting relevant symptoms. First-degree adult relatives of patients with glaucoma should undergo screening annually.

Goldzweig CL et al: Preventing and managing visual disability in primary care: clinical applications. JAMA 2004;291:1497.

REFRACTIVE ERRORS

Refractive errors are the most common cause of blurred vision, and may be a treatable component of poor vision in patients with other diagnoses. In emmetropia (the normal state), objects at infinity are seen clearly with the unaccommodated eye. Objects nearer than infinity are seen with the aid of accommodation, which increases the refractive power of the lens. In hyperopia, objects at infinity are not seen clearly unless accommodation is used, and near objects may not be seen because accommodative capacity is finite. Hyperopia is corrected with plus (convex) lenses. In myopia, the unaccommodated eye brings to a focus images of objects closer than infinity, the distance of such objects from the patient becoming progressively shorter with increasing myopia. Thus, the high myope is able to focus on very near objects without glasses. Objects beyond this distance cannot be seen without the aid of corrective (minus, concave) lenses. In astigmatism, the refractive errors in the horizontal and vertical axes differ.

Various surgical techniques are available for the correction of refractive errors, particularly myopia, including photorefractive keratectomy (PRK), in which the excimer laser is used to reshape the anterior cornea; laser in situ keratomileusis (LASIK) and laser subepithelial keratomileusis (LASEK), in which laser remodeling of the corneal stroma is performed after lifting away a flap of epithelium and stroma (LASIK) or just epithelium (LASEK), which is then replaced; intrastromal corneal ring segments (INTCS); and extraction of the clear crystalline lens. Overall visual outcomes from such procedures are impressive and many individuals seek treatment. However, outcomes for individual cases are not completely predictable, regression of effect from laser surgery may necessitate repeated

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treatment, and there is risk of complications with the possibility of severe permanent visual loss. Topical pirenzepine, a selective muscarinic antagonist, and rigid contact lens wear during sleep (orthokeratology) are also being investigated for myopia.

Presbyopia is the natural loss of accommodative capacity with age. Emmetropes usually notice inability to focus on objects at a normal reading distance at about age 45. Hyperopes experience symptoms at an earlier age. Presbyopia is corrected with plus lenses for near work. Various surgical techniques, particularly insertion of multifocal or accommodative intraocular lenses, are being evaluated.

Use of a pinhole will overcome most refractive errors and thus allows their exclusion as a cause of visual loss. Transient refractive errors occur in patients with diabetes—typically when diabetic control is erratic— and may be the presenting feature. Autoinoculation of scopolamine from seasickness patches or atropine from vials for parenteral use leads to inadvertent pupillary dilation and loss of accommodation.

Claoue C: Functional vision after cataract removal with multifocal and accommodating intraocular lens implantation: prospective comparative evaluation of Array multifocal and 1CU accommodating lenses. J Cataract Refract Surg 2004;30:2088.

Rad AS et al: Progressive keratectasia after laser in situ keratomileusis. J Refract Surg 2004;20:S718.

Rau M et al: Intrastromal corneal ring implantation for the correction of myopia: 12-month follow-up. J Cataract Refract Surg 2003;29:322.

Tan DT et al: One-year multicenter, double-masked, placebocontrolled, parallel safety and efficacy study of 2% pirenzepine ophthalmic gel in children with myopia. Ophthalmology 2005;112:84.

Taneri S et al: Evolution, techniques, clinical outcomes, and pathophysiology of LASEK: review of the literature. Surv Ophthalmol 2004;49:576.

Contact Lenses

Contact lenses are used mostly for correction of refractive errors, for which they often provide a better optical correction than glasses, as well as for management of diseases of the cornea, conjunctiva, or lids. The various types are hard lenses, rigid gas-permeable lenses, and soft lenses. Hard lenses are much more durable and easier to care for than soft lenses but are more difficult to tolerate. Rigid gas-permeable lenses are an effective compromise.

Contact lens care includes cleaning and sterilization whenever the lenses are removed and removal of protein deposits as required. Sterilization is accomplished by thermal or chemical methods. For individuals developing reactions to preservatives in contact lens solutions, preservative-free systems are available. All contact lenses can be inserted in the morning and removed at night. Soft lenses are also available for extended wear. Disposable soft lenses to avoid the necessity for lens cleaning and sterilization are available for daily or extended wear.

The major risk from contact lens wear is corneal ulceration, potentially a blinding condition. Soft lenses present the major hazard, particularly with extended wear, for which there is an approximately eightfold increase in risk of corneal ulceration compared with daily wear. The increased risk from extended wear begins with the first night of overnight wear and increases progressively thereafter. Disposable lenses are also associated with corneal ulceration.

Contact lens wearers should be made aware of the risks they face and ways to minimize them, such as avoiding extended-wear soft lenses and maintaining meticulous lens hygiene, including not using tap water for lens cleaning. Whenever there is ocular discomfort or redness, contact lenses should be removed. Ophthalmologic care should be sought if symptoms persist.

Mah-Sadorra JH et al: Trends in contact lens-related corneal ulcers. Cornea 2005;24:51.

Najjar DM et al: Contact lens-related corneal ulcers in compliant patients. Am J Ophthalmol 2004;137:170.

DISORDERS OF THE LIDS & LACRIMAL APPARATUS

Hordeolum

Hordeolum is a common staphylococcal abscess that is characterized by a localized red, swollen, acutely tender area on the upper or lower lid. Internal hordeolum is a meibomian gland abscess that points onto the conjunctival surface of the lid; external hordeolum or sty is smaller and on the margin.

Warm compresses are helpful. Incision may be indicated if resolution does not begin within 48 hours. An antibiotic ointment (bacitracin or erythromycin) applied to the eyelid every 3 hours may be beneficial during the acute stage. Internal hordeolum may lead to generalized cellulitis of the lid.

Chalazion

Chalazion is a common granulomatous inflammation of a meibomian gland that may follow an internal hordeolum. It is characterized by a hard, nontender swelling on the upper or lower lid with redness and swelling of the adjacent conjunctiva. If the chalazion is large enough to impress the cornea, vision will be distorted. Treatment is by incision and curettage.

Tumors

Verrucae and papillomas of the skin of the lids can often be excised by the general physician if they do not involve the lid margin; otherwise, surgery should be performed by an ophthalmologist so as to avoid permanent notching of the lid. Basal cell epithelioma, squamous cell carcinoma, meibomian gland carcinoma, and malignant melanoma should be excluded by microscopic examination of the excised material since 2% of lesions thought to be benign clinically are found to be malignant. Basal cell epithelioma

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is the most common of these lesions. Mohs' technique of intraoperative examination of excised tissue is particularly valuable in ensuring complete excision of eyelid tumors.

Blepharitis

Blepharitis is a common chronic bilateral inflammatory condition of the lid margins. Anterior blepharitis involves the eyelid skin, eyelashes, and associated glands. It may be ulcerative, because of infection by staphylococci, or seborrheic dermatitis, and associated with seborrhea of the scalp, brows, and ears. Both types may be present. Posterior blepharitis results from inflammation of the meibomian glands. There may be bacterial infection, particularly with staphylococci, or primary glandular dysfunction, in which there is a strong association with acne rosacea.

Symptoms of blepharitis are irritation, burning, and itching. In anterior blepharitis, the eyes are “redrimmed,” and scales or granulations can be seen clinging to the lashes. In posterior blepharitis, the lid margins are hyperemic with telangiectasias; the meibomian glands and their orifices are inflamed, with dilation of the glands, plugging of the orifices, and abnormal secretions. The lid margin is frequently rolled inward to produce a mild entropion, and the tears may be frothy or abnormally greasy.

Blepharitis is a common cause of recurrent conjunctivitis. Both anterior and, more particularly, posterior blepharitis may be complicated by hordeola or chalazions; abnormal lid or lash positions, producing trichiasis; epithelial keratitis of the lower third of the cornea; marginal corneal infiltrates; and inferior corneal vascularization and thinning.

In anterior blepharitis, cleanliness of the scalp, eyebrows, and lid margins is effective local therapy. Scales must be removed from the lids daily with a damp cotton applicator and baby shampoo. An antistaphylococcal antibiotic eye ointment such as bacitracin or erythromycin is applied daily to the lid margins with a cotton-tipped applicator. Antibiotic sensitivity studies may be required in severe staphylococcal blepharitis.

In mild posterior blepharitis, regular meibomian gland expression may be sufficient to control symptoms. Inflammation of the conjunctiva and cornea indicates a need for more active treatment, including long-term low-dose systemic antibiotic therapy, usually with tetracycline (250 mg twice daily), doxycycline (100 mg daily), minocycline (50–100 mg daily) or erythromycin (250 mg three times daily), and short-term topical steroids, eg, prednisolone, 0.125% twice daily. Topical therapy with antibiotics such as ciprofloxacin 0.3% ophthalmic solution twice daily may be helpful but should be restricted to short courses.

Ta CN et al: Effects of minocycline on the ocular flora of patients with acne rosacea or seborrheic blepharitis. Cornea 2003;22:545.

Entropion & Ectropion

Entropion (inward turning of usually the lower lid) occurs occasionally in older people as a result of degeneration of the lid fascia, or may follow extensive scarring of the conjunctiva and tarsus. Surgery is indicated if the lashes rub on the cornea. Botulinum toxin injections may also be used for temporary correction of the involutional lower eyelid entropion of older people.

Ectropion (outward turning of the lower lid) is common with advanced age. Surgery is indicated if there is excessive tearing, exposure keratitis, or a cosmetic problem.

Dacryocystitis

Dacryocystitis is infection of the lacrimal sac due to obstruction of the nasolacrimal system. It may be acute or chronic and occurs most often in infants and in persons over 40 years. It is usually unilateral.

The usual infectious organisms are Staphylococcus aureus and β-hemolytic streptococci in acute dacryocystitis and S epidermidis, anaerobic streptococci, or Candida albicans in chronic dacryocystitis.

Acute dacryocystitis is characterized by pain, swelling, tenderness, and redness in the tear sac area; purulent material may be expressed. In chronic dacryocystitis, tearing and discharge are the principal signs, and mucus or pus may also be expressed.

Acute dacryocystitis responds well to systemic antibiotic therapy. Surgical relief of the underlying obstruction is usually undertaken electively but may be performed acutely. The chronic form may be kept latent with antibiotics, but relief of the obstruction is the only cure. In adults, the standard procedure for obstruction of the lacrimal drainage system is dacryocystorhinostomy, which involves surgical exploration of the lacrimal sac and formation of a fistula into the nasal cavity. Laser-assisted endoscopic dacryocystorhinostomy and balloon dilation or probing of the nasolacrimal system are alternatives. Congenital nasolacrimal duct obstruction often resolves spontaneously but if necessary can be treated by probing of the nasolacrimal system.

Singh Bhinder G et al: Repeated probing results in the treatment of congenital nasolacrimal duct obstruction. Eur J Ophthalmol 2004;14:185.

CONJUNCTIVITIS

Conjunctivitis is the most common eye disease. It may be acute or chronic. Most cases are due to bacterial (including gonococcal and chlamydial) or viral infection. Other causes include keratoconjunctivitis sicca, allergy, chemical irritants, and deliberate self-harm. The mode of transmission of infectious conjunctivitis is usually direct contact via fingers, towels, handkerchiefs, etc, to the fellow eye or to other persons. It may be through contaminated eye drops.

Conjunctivitis must be differentiated from acute uveitis, acute glaucoma, and corneal disorders (Table 7-1).

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Bacterial Conjunctivitis

The organisms isolated most commonly in bacterial conjunctivitis are staphylococci, streptococci (particularly S pneumoniae), Haemophilus species, Pseudomonas, and Moraxella. All may produce a copious purulent discharge. There is no blurring of vision and only mild discomfort. In severe cases, examination of stained conjunctival scrapings and cultures is recommended.

The disease is usually self-limited, lasting about 10–14 days if untreated. A sulfonamide (eg, sulfacetamide, 10% ophthalmic solution or ointment) instilled locally three times daily will usually clear the infection in 2–3 days. Povidone-iodine may also be effective. The use of topical fluoroquinolones is rarely justified for treatment of a generally self-limiting, benign infection.

A. GONOCOCCAL CONJUNCTIVITIS

Gonococcal conjunctivitis, usually acquired through contact with infected genital secretions, is manifested by a copious purulent discharge. It is an ophthalmologic emergency because corneal involvement may rapidly lead to perforation. The diagnosis should be confirmed by stained smear and culture of the discharge. In this disorder, a 5-day course of parenteral ceftriaxone, 1–2 g daily, is required. Topical antibiotics such as erythromycin and bacitracin may be added. In such patients, other sexually transmitted diseases, including chlamydiosis, syphilis, and HIV infection, should be tested for.

B. CHLAMYDIAL KERATOCONJUNCTIVITIS

1. Trachoma

(Chlamydia trachomatis serotypes A–C.) Trachoma is a major cause of blindness worldwide. Recurrent episodes of infection in childhood are manifest as bilateral follicular conjunctivitis, epithelial keratitis, and corneal vascularization (pannus). Cicatrization of the tarsal conjunctiva leads to entropion and trichiasis in adulthood, with secondary central corneal scarring.

Immunologic tests or polymerase chain reaction on conjunctival samples will confirm the diagnosis but treatment should be started on the basis of clinical findings. Single-dose therapy with oral azithromycin, 20 mg/ kg, is effective. Alternatively, oral tetracycline or erythromycin, 250 mg four times a day, or doxycycline, 100 mg twice a day, is given for 3–4 weeks. Local treatment is not necessary. Surgical treatment includes correction of eyelid deformities and corneal transplantation.

2. Inclusion conjunctivitis

(C trachomatis serotypes D–K.) The agent of inclusion conjunctivitis is a common cause of genital tract disease in adults. The eye is usually involved following accidental contact with genital secretions. Adult inclusion conjunctivitis thus occurs most frequently in sexually active young adults. The disease starts with acute redness, discharge, and irritation. The eye findings consist of follicular conjunctivitis with mild keratitis. A nontender preauricular lymph node can often be palpated. Healing usually leaves no sequelae. Diagnosis can be rapidly confirmed by immunologic tests or polymerase chain reaction on conjunctival samples. Treatment is with oral tetracycline or erythromycin, 500 mg four times a day, or doxycycline, 100 mg twice a day, for 3 weeks. Single-dose therapy with azithromycin, 1 g, may also be effective. Before treatment, all cases should be assessed for genital tract infection so that management can be adjusted accordingly, and other venereal diseases sought.

Melese M et al: Feasibility of eliminating ocular Chlamydia trachomatis with repeat mass antibiotic treatments. JAMA 2004;292:721.

Solomon AW et al: Mass treatment with single-dose azithromycin for trachoma. N Engl J Med 2004;351:1962.

Viral Conjunctivitis

One of the most common causes of viral conjunctivitis is adenovirus type 3. Conjunctivitis due to this agent is usually associated with pharyngitis, fever, malaise, and preauricular adenopathy (pharyngoconjunctival fever). Locally, the palpebral conjunctiva is red, and there is a copious watery discharge and scanty exudate. Children are more often affected than adults, and contaminated swimming pools are sometimes the source of infection. The disease usually lasts 10 days.

Epidemic keratoconjunctivitis is caused by adenovirus types 8, 19, 29, and 37. It is more likely to be complicated by visual loss due to corneal subepithelial infiltrates. The disease lasts at least 2 weeks. Local sulfonamide therapy prevents secondary bacterial infection and cold compresses reduce the discomfort of the associated lid edema.

Keratoconjunctivitis Sicca (Dry Eyes)

This is a common disorder, particularly in elderly women. A wide range of conditions predispose to or are characterized by dry eyes. Hypofunction of the lacrimal glands, causing loss of the aqueous component of tears, may be due to aging, hereditary disorders, systemic disease (eg, Sj gren's syndrome), or systemic and topical drugs. Excessive evaporation of tears may be due to environmental factors (eg, a hot, dry, or windy climate) or abnormalities of the lipid component of the tear film, as in blepharitis. Mucin deficiency may be due to malnutrition, infection, burns, or drugs. Hormone replacement therapy may increase the risk of dry eyes.

The patient complains of dryness, redness, or a scratchy feeling of the eyes. In severe cases there is persistent marked discomfort, with photophobia, difficulty in moving the eyelids, and often excessive mucus secretion. In many cases, inspection reveals no abnormality, but on slitlamp examination there are subtle abnormalities of tear film stability and reduced volume of the tear film meniscus along the lower lid. In more severe cases, damaged corneal and conjunctival cells stain with 1% rose bengal, which is to be avoided in severe cases because of the intense pain. In the most severe cases there is marked conjunctival injection, loss of the normal conjunctival

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and corneal luster, epithelial keratitis that may progress to frank ulceration, and mucous strands. Schirmer's test, which measures the rate of production of the aqueous component of tears, may be helpful, but false-positive and false-negative results are frequent.

Treatment depends upon cause. In most early cases, the corneal and conjunctival epithelial changes are reversible. Aqueous deficiency can be treated by replacement of the aqueous component of tears with various types of artificial tears. The simplest preparations are physiologic (0.9%) or hypo-osmotic (0.45%) solutions of sodium chloride. Balanced salt solution is more physiologic but also more expensive. All of these drop preparations can be used as frequently as every half-hour, but in most cases are needed only three or four times a day. More prolonged duration of action can be achieved with drop preparations containing methylcellulose (eg, Isopto Plain) or polyvinyl alcohol (eg, Liquifilm Tears or HypoTears), or by using petrolatum ointment (Lacri-Lube). Such mucomimetics are particularly indicated when there is mucin deficiency. If there is tenacious mucus, mucolytic agents (eg, acetylcysteine, 20% six times daily) may be helpful. The presence of ocular surface and lacrimal gland inflammation in dry eyes has prompted trials of topical antiinflammatory agents such as cyclosporin A.

Lacrimal punctal occlusion by canalicular plugs or surgery is useful in severe cases. Blepharitis is treated as described above. Associated blepharospasm responds to botulinum toxin injections.

Artificial tear preparations are generally very safe and without side effects. However, the preservatives necessary to maintain their sterility are potentially toxic and allergenic and may cause keratitis and cicatrizing conjunctivitis in frequent users. Furthermore, the development of such reactions may be misinterpreted by both the patient and the doctor as a worsening of the dry eye state requiring more frequent use of the artificial tears and leading in turn to further deterioration, rather than being recognized as a need to change to a preservative-free preparation.

Moss SE et al: Incidence of dry eye in an older population. Arch Ophthalmol 2004;122:369.

Pflugfelder SC: Antiinflammatory therapy for dry eye. Am J Ophthalmol 2004;137:337.

Allergic Eye Disease

Allergic eye disease takes a number of different forms but all are expressions of atopy, which may also manifest as atopic asthma, atopic dermatitis, or allergic rhinitis. Symptoms include itching, tearing, redness, stringy discharge, and, occasionally, photophobia and visual loss.

Allergic conjunctivitis is a benign disease, occurring usually in late childhood and early adulthood. It may be seasonal, developing usually during the spring or summer, or perennial. Clinical signs are limited to conjunctival hyperemia and edema (chemosis), the latter at times being marked and sudden in onset. Vernal keratoconjunctivitis also tends to occur in late childhood and early adulthood. It is usually seasonal, with a predilection for the spring. Large “cobblestone” papillae are noted on the upper tarsal conjunctiva. There may be lymphoid follicles at the limbus. Atopic keratoconjunctivitis is a more chronic disorder of adulthood. Both the upper and the lower tarsal conjunctivas exhibit a fine papillary conjunctivitis with fibrosis, resulting in forniceal shortening and entropion with trichiasis. Staphylococcal blepharitis is a complicating factor. Corneal involvement, including refractory ulceration, is frequent during exacerbations of both vernal and atopic keratoconjunctivitis. They may also be complicated by herpes simplex keratitis.

For mild and moderately severe allergic eye disease, a topical histamine H₁-receptor antagonist, such as levocabastine hydrochloride 0.05% or emedastine difumarate 0.05%, or ketorolac tromethamine, a nonsteroidal anti-inflammatory agent, is applied topically four times daily. Ketotifen 0.025%, which has histamine H₁-receptor antagonist, mast cell stabilizer, and eosinophil inhibitor activity, is applied two to four times daily; olopatadine 0.1%, applied twice daily, reduces symptoms by a similar mechanism. Topical mast cell stabilizers, such as cromolyn sodium 4% or lodoxamide tromethamine 0.1%, applied four times daily, or nedocromil sodium 2%, applied twice daily, produce longer-term prophylaxis but the therapeutic response may be delayed. Topical vasoconstrictors and antihistamines are advocated in hay fever conjunctivitis but are of limited efficacy and may produce rebound hyperemia and follicular conjunctivitis. Systemic antihistamines may be useful in prolonged atopic keratoconjunctivitis. Topical corticosteroids are essential to the control of acute exacerbations of both vernal and atopic keratoconjunctivitis. Steroid-induced side effects, including cataracts, glaucoma, and exacerbation of herpes simplex keratitis, are major problems. Topical cyclosporin may be effective. Systemic steroid therapy and even plasmapheresis may be required in severe atopic keratoconjunctivitis. In allergic conjunctivitis, specific allergens may be identifiable and thus avoidable. In vernal keratoconjunctivitis, a cooler climate often provides significant benefit.

Ono SJ et al: Allergic conjunctivitis: update on pathophysiology and prospects for future treatment. J Allergy Clin Immunol 2005;115:118.

Owen CG et al: Topical treatments for seasonal allergic conjunctivitis: systematic review and meta-analysis of efficacy and effectiveness. Br J Gen Pract 2004;54:451.

PINGUECULA & PTERYGIUM

Pinguecula is a yellow elevated nodule on either side of the cornea, more commonly the nasal side, in the area of the palpebral fissure. It is common in persons over age 35 years. Pterygium is a fleshy, triangular encroachment of the conjunctiva onto the nasal side of the cornea and is usually associated with constant exposure to wind, sun, sand, and dust. Pterygium may be either unilateral or bilateral.

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Pingueculae rarely grow, but inflammation (pingueculitis) may occur. No treatment is usually required for pingueculitis or for inflammation of pterygium, but artificial tears are often beneficial, and short courses of topical nonsteroidal anti-inflammatory agents or weak steroids (prednisolone, 0.125% three times a day) may be necessary.

The indications for excision of pterygium are growth threatening vision by approaching the visual axis, marked induced astigmatism, or severe ocular irritation. Recurrence is common and often more aggressive than the primary lesion.

Hirst LW: The treatment of pterygium. Surv Ophthalmol 2003; 48:145.

CORNEAL ULCER

Corneal ulcers are most commonly due to infection by bacteria, viruses, fungi, or amebas. Noninfectious causes—all of which may be complicated by infection— include neurotrophic keratitis (resulting from loss of corneal sensation), exposure keratitis (due to inadequate eyelid closure), severe dry eyes, severe allergic eye disease, and various inflammatory disorders that may be purely ocular or part of a systemic vasculitis. Delayed or ineffective treatment of corneal infection may lead to devastating consequences with intraocular infection or corneal scarring. Prompt referral is essential.

Patients present with pain, photophobia, tearing, and reduced vision. The eye is red, with predominantly circumcorneal injection, and there may be purulent or watery discharge. The corneal appearance varies according to the organisms involved.

Bacterial Keratitis

Bacterial keratitis pursues an aggressive course. Precipitating factors include contact lens wear—especially soft contact lenses worn overnight—and corneal trauma, including laser surgery. The pathogens most commonly isolated are Pseudomonas aeruginosa, Pneumococcus, Moraxella species, and staphylococci. The cornea is hazy, with a central ulcer and adjacent stromal abscess. Hypopyon is often present. The ulcer is scraped to recover material for Gram stain and culture prior to starting treatment with high-concentration topical antibiotics applied hourly day and night for at least the first 24 hours. Fluoroquinolones such as ciprofloxacin 0.3%, ofloxacin 0.3%, and norfloxacin 0.3% are commonly used as first-line agents. Experience with levofloxacin 0.5%, which is more effective against pneumococci than ciprofloxacin, and the fourth-generation fluoroquinolones (moxifloxacin 0.5% and gatifloxacin 0.3%), which are active against mycobacteria, is limited. Gram-positive cocci can also be treated with a cephalosporin such as cefazolin, 100 mg/mL; and gram-negative bacilli with an aminoglycoside such as tobramycin, 15 mg/mL. If no organisms are seen, these two agents can be used together.

Hwang DG: Fluoroquinolone resistance in ophthalmology and the potential role for newer ophthalmic fluoroquinolones. Surv Ophthalmol 2004;49(Suppl 2):S79.

Hyon JY et al: Comparative efficacy of topical gatifloxacin with ciprofloxacin, amikacin, and clarithromycin in the treatment of experimental Mycobacterium chelonae keratitis. Arch Ophthalmol 2004;122:1166.

Mah FS: Fourth-generation fluoroquinolones: new topical agents in the war on ocular bacterial infections. Curr Opin Ophthalmol 2004;15:316.

Herpes Simplex Keratitis

Herpes simplex keratitis is an important cause of ocular morbidity in adults. The ability of the virus to colonize the trigeminal ganglion leads to recurrences precipitated by fever, excessive exposure to sunlight, or immunodeficiency.

The dendritic (branching) ulcer is the most characteristic manifestation of this epithelial keratitis. More extensive (“geographic”) ulcers also occur, particularly if topical corticosteroids have been used. These ulcers are most easily seen after instillation of fluorescein and examination with a blue light. Epithelial disease in itself does not lead to corneal scarring. It responds well to simple debridement and patching. More rapid healing can be achieved by the addition of topical antivirals such as trifluridine drops, vidarabine ointment, acyclovir ointment, or ganciclovir gel. Long-term oral acyclovir reduces the rate of recurrent epithelial disease, for which topical corticosteroids must not be used.

Stromal herpes simplex keratitis produces increasingly severe corneal opacity with each recurrence. Topical antivirals alone are insufficient to control stromal disease. Thus, topical corticosteroids are used in combination, but steroid dependence is a common consequence. Corticosteroids may also enhance viral replication, exacerbating epithelial disease. Oral acyclovir, 200–400 mg five times a day, may be helpful in the treatment of severe herpetic keratitis and for prophylaxis against recurrences, particularly in atopic or HIV-infected individuals. Corneal grafting is necessitated by severe stromal scarring, but the overall outcome is relatively poor. Caution: For patients with known or possible herpetic disease, topical corticosteroids should be prescribed only with ophthalmologic supervision.

Uchoa UB et al: Long-term acyclovir use to prevent recurrent ocular herpes simplex virus infection. Arch Ophthalmol 2003;121:1702.

Wilhelmus KR: Interventions for herpes simplex virus epithelial keratitis. Cochrane Database Syst Rev 2003;3:CD002898.

Fungal Keratitis

Fungal keratitis tends to occur after corneal injury involving plant material or in an agricultural setting, in eyes with chronic ocular surface disease, and in contact lens wearers. It is an indolent process, with the cornea characteristically having multiple stromal abscesses and relatively little epithelial loss. Intraocular infection

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is common. Corneal scrapings are cultured on media suitable for fungi whenever the history or corneal appearance is suggestive of fungal disease.

Srinivasan M: Fungal keratitis. Curr Opin Ophthalmol 2004;15:321.

Acanthamoeba Keratitis

Acanthamoeba is an important cause of suppurative keratitis in contact lens wearers. Although severe pain with perineural and ring infiltrates in the corneal stroma is characteristic, earlier forms with changes confined to the corneal epithelium are identifiable. Culture requires specialized media. Treatment is hampered by the organism's ability to encyst within the corneal stroma. Various agents have been used, including neomycin-polymyxin-gramicidin, chlorhexidine, the investigational agents propamidine isethionate and polyhexamethyl biguanide, and oral and topical imidazoles such as ketoconazole, miconazole, and itraconazole. Epithelial debridement may be useful in early infections. Corneal grafting may be required in the acute stage to arrest the progression of infection or after resolution to restore vision. Systemic immunosuppression may be needed if there is scleral involvement.

Kilvington S et al: Acanthamoeba keratitis: the role of domestic tap water contamination in the United Kingdom. Invest Ophthalmol Vis Sci 2004;45:165.

Herpes Zoster Ophthalmicus

Herpes zoster frequently involves the ophthalmic division of the trigeminal nerve. It presents with malaise, fever, headache, and periorbital burning and itching. These symptoms may precede the eruption by a day or more. The rash is initially vesicular, quickly becoming pustular and then crusting. Involvement of the tip of the nose or the lid margins predicts involvement of the eye. Ocular signs include conjunctivitis, keratitis, episcleritis, and anterior uveitis, often with elevated intraocular pressure. Recurrent anterior segment inflammation, neurotrophic keratitis, and posterior subcapsular cataract are long-term complications. Optic neuropathy, cranial nerve palsies, acute retinal necrosis, and cerebral angiitis are infrequent problems in the acute stage. HIV infection is an important risk factor for herpes zoster ophthalmicus and increases the likelihood of complications.

High-dose oral acyclovir (800 mg five times a day), valacyclovir (1 g three times a day), or famciclovir (250–500 mg three times a day) started within 72 hours after the appearance of the rash reduces the incidence of ocular complications but not of postherpetic neuralgia. Anterior uveitis requires treatment with topical corticosteroids and cycloplegics. Neurotrophic keratitis is an important cause of long-term morbidity.

Liesegang TJ: Herpes zoster virus infection. Curr Opin Ophthalmol 2004;15:531.

Zaal MJ et al: Prognostic value of Hutchinson's sign in acute herpes zoster ophthalmicus. Graefes Arch Clin Exp Ophthalmol 2003;241:187.

ACUTE ANGLE-CLOSURE GLAUCOMA

ESSENTIALS OF DIAGNOSIS

Rapid onset in older age groups, particularly hyperopes and Asians.
Severe pain and profound visual loss with “halos around lights.”
Red eye, steamy cornea, dilated pupil.
Hard eye to palpation.

General Considerations

Primary acute angle-closure glaucoma occurs only with closure of a preexisting narrow anterior chamber angle, found in elderly persons (owing to enlargement of the lens), hyperopes, and Asians. In the United States, about 1% of people over age 35 years have narrow anterior chamber angles, but many never develop acute glaucoma. Angle closure may be precipitated by pupillary dilation and thus can occur from sitting in a darkened theater, at times of stress, or, rarely, from pharmacologic mydriasis. Anticholinergic or sympathomimetic agents (eg, nebulized bronchodilators, atropine for preoperative medication, antidepressants, or nasal decongestants) are also causes. Secondary acute angle-closure glaucoma may be observed with anterior uveitis, dislocation of the lens, or topiramate therapy. Symptoms are the same as in primary acute angle-closure glaucoma, but differentiation is important because of differences in management. Chronic angleclosure glaucoma is particularly common in eastern Asia. It presents in the same way as open-angle glaucoma (see below).

Clinical Findings

Patients with acute glaucoma usually seek treatment immediately because of extreme pain and blurred vision, though there are subacute cases. The blurred vision is associated with halos around lights. Nausea and abdominal pain may occur, and acute glaucoma must be remembered in the differential diagnosis of the acute abdomen. The eye is red, the cornea steamy, and the pupil moderately dilated and nonreactive to light. Intraocular pressure is usually over 40 mm Hg.

Differential Diagnosis

Acute glaucoma must be differentiated from conjunctivitis, acute uveitis, and corneal disorders (Table 7-1).

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Treatment

A. PRIMARY

Initial treatment in primary angle-closure glaucoma is control of intraocular pressure. A single 500-mg intravenous dose of acetazolamide, followed by 250 mg orally four times a day, is usually sufficient. Osmotic diuretics such as oral glycerol and intravenous urea or mannitol—the dosage of all three being 1–2 g/kg—may be necessary if there is no response to acetazolamide. Laser therapy to the peripheral iris (iridoplasty) or anterior chamber paracentesis is also effective. Once the intraocular pressure has started to fall, topical 4% pilocarpine, 1 drop every 15 minutes for 1 hour and then four times a day, is used to reverse the underlying angle closure. The definitive treatment is laser peripheral iridotomy or surgical peripheral iridectomy, which should also be performed prophylactically on the fellow eye. Cataract extraction is a possible alternative. If it is not possible to control the intraocular pressure medically, glaucoma drainage surgery as for uncontrolled open-angle glaucoma (see below) may be required.

B. SECONDARY

In secondary acute angle-closure glaucoma, systemic acetazolamide is also used, with or without osmotic agents. Further treatment is determined by the cause.

Prognosis

Untreated acute angle-closure glaucoma results in severe and permanent visual loss within 2–5 days after onset of symptoms. Affected patients need to be kept under review for development of chronic glaucoma.

Aung T et al: Long-term outcomes in Asians after acute primary angle closure. Ophthalmology 2004;111:1464.

Fraunfelder FW et al: Topiramate-associated acute, bilateral, secondary angle-closure glaucoma. Ophthalmology 2004;111:109.

Saw SM et al: Awareness of glaucoma, and health beliefs of patients suffering primary acute angle closure. Br J Ophthalmol 2003;87:446.

CHRONIC GLAUCOMA

ESSENTIALS OF DIAGNOSIS

No symptoms in early stages.
Gradual loss of peripheral vision over a period of years, resulting in tunnel vision.
Insidious progression in older age groups.
Pathologic cupping of the optic disks usually associated with persistent elevation of intraocular pressure.

General Considerations

Chronic glaucoma is characterized by gradually progressive—over a period of months or years—excavation (“cupping”) and pallor of the optic disk with loss of vision varying from slight constriction of the peripheral fields to complete blindness. In chronic openangle glaucoma, the intraocular pressure is elevated due to reduced drainage of aqueous through the trabecular meshwork. In chronic angle-closure glaucoma, flow of aqueous into the anterior chamber angle is obstructed. In normal-tension glaucoma, intraocular pressure is not elevated above the normal range but the same pattern of optic nerve damage occurs, probably due to vascular insufficiency.

The cause of the reduced drainage of aqueous in primary open-angle glaucoma has not been clearly established. A number of mutations, such as in the myocilin gene on chromosome 1, have been identified in a small proportion of cases. The disease is bilateral, and there is an increased prevalence in first-degree relatives of affected individuals and in diabetics. In blacks, primary open-angle glaucoma is more frequent, occurs at an earlier age, and results in more severe optic nerve damage. Secondary open-angle glaucoma may result from uveitis or the effects of trauma. Elevation of intraocular pressure is also a complication of steroid therapy, whether it be topical, systemic, inhaled, or administered by nasal spray.

In the United States, it is estimated that 2% of people over 40 years of age have glaucoma, affecting more than 2 million individuals and being three times more prevalent in blacks. At least 25% of cases are undetected. Over 90% of cases are of the open-angle type, either primary open-angle or normal-tension glaucoma. Worldwide, about 50% of all cases of glaucoma are due to acute (see above) or chronic angle closure due to the very high prevalence of angle closure in Asians.

Clinical Findings

Because patients with chronic glaucoma have no symptoms initially, diagnosis is often made incidentally at routine eye tests. On examination, there may be slight cupping of the optic disk observed as an absolute increase—or an asymmetry between the two eyes—of the ratio of the diameter of the optic cup to the diameter of the whole optic disk (cup-disk ratio). (Cup-disk ratio of greater than 0.5 or asymmetry of cup-disk ratio of 0.2 or more is suggestive.) Changes in the retinal nerve fiber layer may be observed as an earlier finding in some patients. The visual fields gradually constrict, but central vision remains good until late in the disease.

Diagnosis requires consistent and reproducible abnormalities in at least two out of three parameters— intraocular pressure, optic disc cupping, and central visual field. The normal range of intraocular pressure is 10–21 mm Hg. In many individuals, elevated intraocular pressure is not associated with optic disk or

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visual field abnormalities. These ocular hypertensives are at increased risk of developing glaucomatous damage. Treatment to reduce intraocular pressure is justified if there is a moderate to high risk of the development of glaucoma. Risk is determined by several factors, including age, optic disk appearance, level of intraocular pressure, and corneal thickness. Conversely, a significant proportion of patients with glaucoma have normal intraocular pressure when it is first measured, and only repeated measurements identify the abnormally high pressure. Furthermore, in patients with normal-tension glaucoma, the intraocular pressure is always within the normal range despite repeated measurement. There are many other causes of optic disk abnormalities or visual field changes that mimic glaucomatous damage, and visual field testing may prove unreliable in some patients, particularly the elderly. Taken together, these factors mean that the diagnosis of glaucoma is not always straightforward, hampering the effectiveness of screening programs.

Prevention

All persons over age 40 years should have intraocular pressure measurement and optic disc examination every 2–5 years. In diabetics and in individuals with a family history of glaucoma, annual examination is indicated.

Treatment

The prostaglandin analogs (latanoprost 0.005%, bimatoprost 0.03%, and travoprost 0.004% once daily at night; or unoprostone isopropyl 0.15% twice daily) are commonly used as first-line therapy because of their efficacy, the convenience of once-daily administration, and their lack of systemic side effects. All may produce conjunctival hyperemia, permanent darkening of the iris and eyebrow color, and eyelash growth. Latanoprost has been associated with reactivation of uveitis and macular edema. Topical β-adrenergic blocking agents such as timolol 0.25% or 0.5%, carteolol 1%, levobunolol 0.5%, and metipranolol 0.3% solutions twice daily or timolol 0.5% gel once daily may be used alone or in combination with a prostaglandin analog. They are contraindicated in patients with reactive airway disease or heart failure. Betaxolol, 0.25% or 0.5%, a β-receptor selective blocking agent, is theoretically safer in reactive airway disease but less effective at reducing intraocular pressure. Brimonidine 0.2%, a selective α₂-agonist, and dorzolamide 2% or brinzolamide 1%, topical carbonic anhydrase inhibitors, also can be used in addition to a prostaglandin analog or a β-blocker (twice daily) or as initial therapy when prostaglandin analogs and β-blockers are contraindicated (brimonidine twice daily, dorzolamide and brinzolamide three times daily). Both are associated with allergic reactions. The combination drops Xalacom (latanoprost 0.005% and timolol 0.5%) used once daily in the morning and Cosopt (dorzolamide 2% and timolol 0.5%) used twice daily improve compliance when multiple medications are required.

Apraclonidine, 0.5–1%, another α₂-agonist, can be used three times a day to postpone the need for surgery in patients receiving maximal medical therapy, but long-term use is limited by drug reactions. It is more commonly used to control acute rises in intraocular pressure such as after laser therapy. Epinephrine, 0.5–1%, and the prodrug dipivefrin, 0.1%, are being used much less frequently because of adverse effects on the outcome of subsequent glaucoma surgery. Pilocarpine 1–4% (and sometimes higher concentrations in patients with dark irides) four times a day is little used because of the induced myopia in younger patients and the pupillary constriction that compromises vision in patients with cataract. Oral carbonic anhydrase inhibitors (eg, acetazolamide) may still be used on a long-term basis if topical therapy is inadequate and surgical or laser therapy is inappropriate.

Laser trabeculoplasty is used as an adjunct to topical therapy to defer surgery and is also advocated as primary treatment. Surgery is generally undertaken when intraocular pressure is inadequately controlled by medical and laser therapy, but it may also be used as primary treatment. Trabeculectomy remains the standard procedure. Adjunctive treatment with subconjunctival fluorouracil or mitomycin is used perior postoperatively in difficult cases. Viscocanalostomy and deep sclerectomy with collagen implant—two alternative procedures that avoid a full-thickness incision into the eye—may be as effective as trabeculectomy but are more difficult to perform.

In chronic angle-closure glaucoma, laser peripheral iridotomy or surgical peripheral iridectomy may be helpful in the early stages.

Prognosis

Untreated chronic glaucoma that begins at age 40–45 years will probably cause complete blindness by age 60–65. Early diagnosis and treatment can preserve useful vision throughout life. In primary open-angle glaucoma—and if treatment is required in ocular hypertension—the aim is to reduce intraocular pressure to a level that will adequately reduce progression of visual field loss. In eyes with marked visual field or optic disk changes, intraocular pressure must be reduced to less than 16 mm Hg. In normal-tension glaucoma with progressive visual field loss, it is necessary to achieve even lower intraocular pressure such that surgery is often required.

Bonovas S et al: Diabetes mellitus as a risk factor for primary openangle glaucoma: a meta-analysis. Diabet Med 2004;21:609.

Cohen CS et al: The dawn of genetic testing for glaucoma. Curr Opin Ophthalmol 2004;15:75.

Friedman DS et al: Eye Diseases Prevalence Research Group. Prevalence of open-angle glaucoma among adults in the United States. Arch Ophthalmol 2004;122:532.

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Higginbotham EJ et al: The Ocular Hypertension Treatment Study: topical medication delays or prevents primary openangle glaucoma in African American individuals. Arch Ophthalmol 2004;122:813.

Weinreb RN et al: Primary open-angle glaucoma. Lancet 2004;363:1711.

Wong EY et al: Detection of undiagnosed glaucoma by eye health professionals. Ophthalmology 2004;111:1508.

UVEITIS

Uveitis means inflammation of the uveal tract, which is formed by the iris (iritis), ciliary body (cyclitis), and choroid (choroiditis). Inflammatory eye disease may also originate primarily in the retina (retinitis) or retinal blood vessels (retinal vasculitis).

Intraocular inflammation is classified as anterior uveitis, posterior uveitis, or panuveitis. Uveitis may also be termed acute or chronic and granulomatous or nongranulomatous. In most cases the pathogenesis of uveitis is primarily immunologic, but in immunodeficiency states infection may be the cause.

Clinical Findings

Anterior uveitis is characterized by inflammatory cells and flare within the aqueous. In severe cases, there may be hypopyon (layered collection of white cells) and fibrin within the anterior chamber. Cells may also be seen on the corneal endothelium as keratic precipitates (KPs). In granulomatous uveitis, these are large “mutton-fat” KPs, and iris nodules may be seen. In nongranulomatous uveitis, the KPs are smaller and iris nodules are not seen. The pupil is usually small, and with the development of posterior synechiae (adhesions between the iris and anterior lens capsule), it also becomes irregular.

Nongranulomatous anterior uveitis tends to present acutely with unilateral pain, redness, photophobia, and visual loss. Granulomatous anterior uveitis is more indolent, causing blurred vision in a mildly inflamed eye.

In posterior uveitis, there are cells in the vitreous. Inflammatory lesions may be present in the retina or choroid. Fresh lesions are yellow, with indistinct margins, whereas older lesions have more definite margins and are commonly pigmented. Retinal vessel sheathing may occur adjacent to such lesions or more diffusely. In severe cases, vitreous opacity precludes visualization of retinal details.

Posterior uveitis tends to present with gradual visual loss in a relatively quiet eye. Bilateral involvement is common. Visual loss may be due to vitreous haze and opacities, inflammatory lesions involving the macula, macular edema, retinal vein occlusion, or, rarely, associated optic neuropathy.

Etiology

The systemic disorders associated with acute nongranulomatous anterior uveitis are the HLA-B27related conditions ankylosing spondylitis, reactive arthritis, psoriasis, ulcerative colitis, and Crohn's disease. Beh et's syndrome produces both anterior uveitis with recurrent hypopyon in 5% of patients and posterior uveitis with retinal vein occlusions on occasion. Both herpes simplex and herpes zoster infections may cause nongranulomatous anterior uveitis.

Diseases producing granulomatous anterior uveitis also tend to be causes of posterior uveitis. These include sarcoidosis, tuberculosis, syphilis, toxoplasmosis, Vogt-Koyanagi-Harada syndrome (bilateral uveitis associated with alopecia, poliosis [depigmented eyelashes, eyebrows, or hair], vitiligo, and hearing loss), and sympathetic ophthalmia following penetrating ocular trauma. Syphilis produces a characteristic “salt and pepper” fundus, often with surprisingly little visual loss unless there is also primary syphilitic optic atrophy. In congenital toxoplasmosis, there is usually evidence of previous episodes of retinochoroiditis. The principal agents responsible for ocular inflammation in AIDS are cytomegalovirus, herpes simplex and herpes zoster viruses, mycobacteria, cryptococcus, toxoplasma, and candida.

Autoimmune retinal vasculitis and pars planitis (intermediate uveitis) are idiopathic conditions that produce posterior uveitis.

Retinal detachment, intraocular tumors, and central nervous system lymphoma may all masquerade as uveitis.

Treatment

Anterior uveitis will usually respond to topical corticosteroids. Occasionally, periocular steroid injections or even systemic steroids may be required. Dilation of the pupil is important to relieve discomfort and prevent posterior synechiae.

Posterior uveitis more commonly requires systemic corticosteroid therapy and occasionally systemic immunosuppression with agents such as azathioprine or cyclosporine. Pupillary dilation is not usually necessary.

If an infectious cause is identified, specific antimicrobial therapy may be indicated. In general, the prognosis for anterior uveitis, particularly the nongranulomatous type, is better than that for posterior uveitis.

Fernandez-Melon J et al: Uveitis as the initial clinical manifestation in patients with spondyloarthropathies. J Rheumatol 2004;31:524.

Monnet D et al: Ophthalmic findings and frequency of extraocular manifestations in patients with HLA-B27 uveitis: a study of 175 cases. Ophthalmology 2004;111:802.

Smith JR: Management of uveitis. Clin Exp Med 2004;4:21.

Tugal-Tutkun I et al: Uveitis in Behcet disease: an analysis of 880 patients. Am J Ophthalmol 2004;138:373.

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CATARACT

ESSENTIALS OF DIAGNOSIS

Blurred vision, progressive over months or years.
No pain or redness.
Lens opacities (may be grossly visible).

General Considerations

Cataract is a lens opacity. Cataracts are usually bilateral. They may be congenital (owing to intrauterine infections such as rubella and cytomegalovirus, or inborn errors of metabolism such as galactosemia); traumatic; or secondary to systemic disease (diabetes, myotonic dystrophy, atopic dermatitis), systemic or inhaled corticosteroid treatment, or uveitis. Senile cataract is by far the most common type; most persons over age 60 have some degree of lens opacity. Cigarette smoking increases the risk of cataract formation.

Clinical Findings

Even in its early stages, a cataract can be seen through a dilated pupil with an ophthalmoscope or slitlamp. As the cataract matures, the retina will become increasingly more difficult to visualize, until finally the fundus reflection is absent and the pupil is white.

Treatment

Functional visual impairment is the prime criterion for surgery. The cataract is usually removed by one of the techniques in which the delicate posterior lens capsule remains (extracapsular). Laser treatment may be required subsequently if the posterior capsule opacifies. Ultrasonic fragmentation (phacoemulsification) of the lens nucleus allows cataract surgery to be performed through a small incision without the need for sutures, thus reducing the postoperative complication rate and accelerating visual rehabilitation.

It is routine practice to insert an intraocular lens at the time of surgery. This dispenses with the need for heavy cataract glasses or contact lenses. Multifocal and accommodative intraocular lenses have been used with some success to reduce the need for both distance and reading glasses.

Prognosis

If surgery is indicated, lens extraction improves visual acuity in 95% of cases and can have a profound impact on quality of life, although expectations must be realistic. The remainder either have preexisting retinal damage or develop perioperative or postoperative complications.

Dick HB: Accommodative intraocular lenses: current status. Curr Opin Ophthalmol 2005;16:8.

Harwood RH et al: Falls and health status in elderly women following first eye cataract surgery: a randomized controlled trial. Br J Ophthalmol 2005;89:53.

Pager CK: Expectations and outcomes in cataract surgery: a prospective test of 2 models of satisfaction. Arch Ophthalmol 2004;122:1788.

Shichi H: Cataract formation and prevention. Expert Opin Investig Drugs 2004;13:691.

RETINAL DETACHMENT

ESSENTIALS OF DIAGNOSIS

Blurred vision in one eye becoming progressively worse.
No pain or redness.
Detachment seen by ophthalmoscopy.

General Considerations

The primary event in rhegmatogenous retinal detachment is the development of a retinal tear. This is usually spontaneous, related to changes in the vitreous, but may be secondary to trauma. Spontaneous detachment occurs most frequently in persons over 50 years of age. Myopia and cataract extraction are the two most common predisposing causes. Once there is a tear in the retina, fluid vitreous is able to pass through the tear and lodge behind the sensory retina. This, combined with vitreous traction and the pull of gravity, results in progressive detachment. The superior temporal area is the most common site of detachment. The area involved rapidly increases, causing corresponding progressive visual loss. Central vision remains intact until the macula becomes detached.

The basis of traction retinal detachment is the development of preretinal fibrosis, such as in association with proliferative retinopathy secondary to diabetic retinopathy or retinal vein occlusion. Serous retinal detachment results from accumulation of subretinal fluid, such as in exudative age-related macular degeneration or secondary to choroidal tumors.

Clinical Findings

On ophthalmoscopic examination in rhegmatogenous retinal detachment, the retina is seen hanging in the vitreous like a gray cloud. One or more retinal tears will usually be found on further examination. In traction retinal detachment, there is irregular retinal elevation with fibrosis. With serous retinal detachment, the retina is dome-shaped and the subretinal fluid may shift position with changes in posture.

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Treatment

All cases of retinal detachment must be referred immediately to an ophthalmologist. During transportation, the patient's head is positioned so that the detached portion of the retina will fall back with the aid of gravity. Treatment of rhegmatogenous retinal detachment is directed at closing the tears. A permanent adhesion between the neurosensory retina, the retinal pigment epithelium, and the choroid is produced in the region of the tears by applying cryotherapy to the sclera or laser photocoagulation to the retina. To achieve apposition of the neurosensory retina to the retinal pigment epithelium while this adhesion is developing, indentation of the sclera with a silicone sponge or buckle; subretinal fluid drainage via an incision in the sclera; and injection of an expansile gas into the vitreous cavity may be required. Certain types of uncomplicated retinal detachment may be treated by pneumatic retinopexy, in which an expansile gas is initially injected into the vitreous cavity followed by positioning of the patient's head to facilitate reattachment of the retina. Once the retina is repositioned, the tear is sealed by laser photocoagulation or cryotherapy. All the stages of pneumatic retinopexy can be performed under local anesthesia as an office procedure. The last stage is the same as is used to seal retinal tears without associated detachment as prophylaxis against recurrence.

In complicated retinal detachments—particularly those in which fibroproliferative tissue has developed on the surface of the retina or within the vitreous cavity, ie, traction retinal detachments—retinal reattachment can be accomplished only by removal of the vitreous, direct manipulation of the retina, and internal tamponade of the retina with air, expansile gases, or even silicone oil. (The presence of an expansile gas within the eye is a contraindication to air travel, mountaineering at high altitude, and nitrous oxide anesthesia. Such gases persist in the globe for weeks after surgery.) (See Chapter 38.) Treatment of serous retinal detachments is determined by the underlying cause.

Prognosis

About 80% of uncomplicated rhegmatogenous retinal detachments can be cured with one operation; an additional 15% will need repeated operations; and the remainder never reattach. The prognosis is worse if the macula is detached or if the detachment is of long duration. Without treatment, retinal detachment often becomes total within 6 months. Spontaneous detachments are ultimately bilateral in up to 25% of cases.

Gariano RF et al: Evaluation and management of suspected retinal detachment. Am Fam Physician 2004;69:1691.

Lee EJ: Use of nitrous oxide causing severe visual loss 37 days after retinal surgery. Br J Anaesth 2004;93:464.

VITREOUS HEMORRHAGE

Patients with vitreous hemorrhage complain of sudden visual loss, abrupt onset of floaters that may progressively increase in severity, or, occasionally, “bleeding within the eye.” Visual acuity ranges from 20/20 to light perception only. The eye is not inflamed, and the clue to diagnosis is the inability to see fundal details clearly despite the presence of a clear lens. Causes of vitreous hemorrhage include diabetic retinopathy, retinal tears (with or without detachment), retinal vein occlusions, exudative age-related macular degeneration, blood dyscrasias, trauma, and subarachnoid hemorrhage. In all cases, examination by an ophthalmologist is essential. Retinal tears and detachments necessitate urgent treatment (see above).

AGE-RELATED MACULAR DEGENERATION

Age-related macular degeneration is the leading cause of permanent visual loss in the elderly. The exact cause is unknown, but the incidence increases with each decade over age 50 years (to almost 30% by age 75). Other associations in addition to age include race (usually white), sex (slight female predominance), family history, and a history of cigarette smoking.

Age-related macular degeneration includes a broad spectrum of clinical and pathologic findings that can be classified into two groups: atrophic (“dry”) and exudative (“wet”). Although both are progressive and usually bilateral, they differ in manifestations, prognosis, and management. The precursor to age-related macular degeneration is age-related maculopathy, the hallmark of which is the development of retinal drusen. Hard drusen appear ophthalmoscopically as discrete yellow deposits, usually in the macular region. Soft drusen are larger, paler, and less distinct. Large, confluent soft drusen are particularly associated with exudative age-related macular degeneration.

Atrophic degeneration is characterized by gradually progressive bilateral visual loss of moderate severity due to atrophy and degeneration of the outer retina, retinal pigment epithelium, Bruch's membrane, and choriocapillaris. In exudative degeneration, visual loss is of more rapid onset and greater severity, and the two eyes are frequently affected sequentially over a period of a few years. The exudative form accounts for about 90% of all cases of legal blindness due to this disorder. Impairment of the barrier function of Bruch's membrane (between the retinal pigment epithelium and the choriocapillaris) allows serous fluid or blood to leak into the retina to produce elevation of the retinal pigment epithelium from Bruch's membrane (retinal pigment epithelial detachment) or separation of the neurosensory retina from the retinal pigment epithelium (serous retinal detachment). These changes may resolve spontaneously, with variable visual outcome, but are often associated with neovascularization arising from the

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choroidal vessels and extending between the retinal pigment epithelium and Bruch's membrane (subretinal neovascular membrane). This membrane produces permanent visual loss.

Sudden visual loss in patients with exudative agerelated macular degeneration occurs at the time of pigment epithelial or sensory retinal detachment or hemorrhage from a subretinal neovascular membrane. All these changes may occur in previously undiagnosed patients, in patients known to have atrophic changes, and in the other eye of patients with exudative disease. Laser photocoagulation of subretinal neovascular membranes may delay the onset of permanent visual loss but only when the membrane is far enough away from the fovea to permit such treatment, which is relatively infrequent. Conventional laser photocoagulation of subfoveal neovascular membranes is associated with an inevitable immediate reduction in vision because of associated retinal damage. Photodynamic laser therapy (PDT), involving intravenous injection of verteporfin activated by subsequent laser irradiation to produce cytotoxic derivatives that induce selective vascular damage, is particularly indicated when the neovascular membrane is well defined (“classic”) and may be helpful when it is not (“occult”). Treatment often needs to be repeated, but the relatively high cost can limit ongoing therapy. Various surgical techniques to excise subfoveal neovascular membranes—or to reposition the macula away from them—continue to be investigated. Older patients developing sudden visual loss due to macular disease—particularly paracentral distortion or scotoma with preservation of central acuity—should be referred urgently to an ophthalmologist for assessment.

There is no specific treatment for atrophic age-related macular degeneration, but—as with the exudative form—patients often benefit from low vision aids. The disorder results in loss of central vision only. Peripheral fields and hence navigational vision are always maintained, though these may become impaired by cataract formation for which surgery may be helpful. The value of oral antioxidants and other dietary supplements in preventing visual loss in age-related macular degeneration continues to be assessed.

Klein R et al: The epidemiology of age-related macular degeneration. Am J Ophthalmol 2004;137:486.

Liu M et al: A review of treatments for macular degeneration: a synopsis of currently approved treatments and ongoing clinical trials. Curr Opin Ophthalmol 2004;15:221.

Meads C et al: Photodynamic therapy with verteporfin is effective, but how big is its effect? Results of a systematic review. Br J Ophthalmol 2004;88:212.

Moshfeghi DM et al: Age-related macular degeneration: evaluation and treatment. Cleve Clin J Med 2003;70:1017.

Zarbin MA: Current concepts in the pathogenesis of age-related macular degeneration. Arch Ophthalmol 2004;122:598.

CENTRAL & BRANCH RETINAL VEIN OCCLUSIONS

The severity of visual loss in central retinal vein occlusion is variable. The visual impairment is commonly first noticed upon waking. Ophthalmoscopic signs include disk swelling, venous dilation and tortuosity, retinal hemorrhages, and cotton-wool spots.

In those with initially good acuity (20/60 or better), the visual prognosis is good. With poor initial acuity (20/200 or worse), extensive hemorrhages and multiple cotton-wool spots indicate widespread retinal ischemia, which can be confirmed by demonstrating extensive areas of capillary closure on fluorescein angiography. These eyes are at high risk of developing neovascular (rubeotic) glaucoma, typically within 3 months after venous occlusion, and should be monitored by an ophthalmologist so that laser panretinal photocoagulation can be undertaken if it occurs. Visual prognosis in such cases is poor. Improvement in vision has been reported in central retinal vein occlusion after direct injection of tissue plasminogen activator into the retinal venous system, incision of the sclera at the edge of the optic disk (radial optic neurotomy), and intravitreal corticosteroid injection when macular edema is present.

Branch retinal vein occlusions may present in a variety of ways. Sudden loss of vision may occur at the time of occlusion if the fovea is involved or some time afterward from vitreous hemorrhage due to retinal new vessels. More gradual visual loss may occur with development of macular edema.

In acute branch retinal vein occlusion there are signs similar to those of central retinal vein occlusion but affecting only the retina drained by the obstructed vein. If retinal neovascularization develops, the areas of ischemic retina should be laser photocoagulated. Macular edema may respond to laser treatment or possibly vitrectomy with surgical incision of the retinal vascular adventitia (arteriovenous sheathotomy) and injection of tissue plasminogen activator.

All patients with retinal vein occlusion should be referred urgently to an ophthalmologist. They should be screened for diabetes, systemic hypertension, hyperlipidemia, and glaucoma. In younger patients, antiphospholipid antibodies, inherited thrombophilia, and hyperhomocysteinemia should be excluded. Hyperviscosity syndromes are rarely associated with retinal vein occlusions but may worsen their prognosis.

Bashshur ZF et al: Intravitreal triamcinolone for the management of macular edema due to nonischemic central retinal vein occlusion. Arch Ophthalmol 2004;122:1137.

Charbonnel J et al: Management of branch retinal vein occlusion with vitrectomy and arteriovenous adventitial sheathotomy, the possible role of surgical posterior vitreous detachment. Graefes Arch Clin Exp Ophthalmol 2004;242:223.

Garcia-Arumi J: Management of macular edema in branch retinal vein occlusion with sheathotomy and recombinant tissue plasminogen activator. Retina 2004;24:530.

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Mason J 3rd et al: Sheathotomy to decompress branch retinal vein occlusion: a matched control study. Ophthalmology 2004;111:540.

CENTRAL & BRANCH RETINAL ARTERY OCCLUSIONS

Central retinal artery occlusion presents as sudden profound monocular visual loss. Visual acuity is reduced to counting fingers or worse, and visual field is restricted to an island of vision in the temporal field. Ophthalmoscopy reveals pallid swelling of the retina, most obvious in the posterior segment, with a cherryred spot at the fovea. The retinal arteries are attenuated, and “box-car” segmentation of blood in the veins may be seen. Occasionally, emboli are seen in the central retinal artery or its branches. The retinal swelling subsides over a period of 4–6 weeks, leaving a relatively normal retinal appearance but a pale optic disk and attenuated arterioles.

The patient is referred emergently to an ophthalmologist. If seen within a few hours after onset, emergency treatment—including laying the patient flat, ocular massage, high concentrations of inhaled oxygen, intravenous acetazolamide, and anterior chamber paracentesis—may influence the visual outcome. Studies of thrombolysis, particularly by local intra-arterial injection but also intravenously, have shown variable results.

Branch retinal artery occlusion may also present with sudden loss of vision if the fovea is involved, but more commonly sudden loss of visual field is the presenting complaint. Fundal signs of retinal swelling and adjacent cotton-wool spots are limited to the area of retina supplied by the occluded vessel. Patients with branch retinal artery occlusions should be referred urgently to an ophthalmologist.

Giant cell arteritis must be excluded in patients 55 years of age or older, especially because of the risk— highest in the first few days—of involvement of the other eye. If giant cell arteritis is suspected, either by clinical features, particularly jaw claudication, or markedly elevated serum inflammatory markers, usually erythrocyte sedimentation rate and C-reactive protein, immediately institute high-dose corticosteroids (oral prednisolone 1–1.5 mg/kg/d, if necessary preceded by intravenous hydrocortisone 250–500 mg stat) and proceed promptly to temporal artery biopsy. In patients with bilateral visual loss, initial treatment with methylprednisolone 1 g/d for 1–3 days should be considered.

In central and particularly in branch retinal artery occlusion, carotid and cardiac sources of emboli must be identified so that appropriate treatment is given to reduce the risk of stroke (see Chapter 12). Migraine, oral contraceptives, systemic vasculitis, congenital or acquired thrombophilia, and hyperhomocysteinemia should be considered in young patients, internal carotid artery dissection when there is neck pain or a recent history of neck trauma, and diabetes, hyperlipidemia, and systemic hypertension in all patients.

Lichtstein DM et al: Heeding clues to giant cell arteritis. Prompt response can prevent vision loss. Postgrad Med 2004;115: 91.

Yuzurihara D et al: Visual outcome in central retinal and branch retinal artery occlusion. Jpn J Ophthalmol 2004;48:490.

AMAUROSIS FUGAX

Amaurosis fugax (“fleeting blindness”) is usually caused by retinal emboli from ipsilateral carotid disease. The visual loss is usually described as a curtain passing vertically across the visual field with complete monocular visual loss lasting a few minutes and a similar curtain effect as the episode passes. To reduce the risk of stroke, patients with high-grade stenosis (70–99%) of the ipsilateral internal carotid artery should be considered for carotid endarterectomy or angioplasty with stenting. Patients with medium-grade (30–69%) stenosis, unless there are other risk factors for stroke, or low-grade (up to 29%) stenosis are generally better treated medically with aspirin or other antiplatelet drugs. The most reliable method of evaluating carotid stenosis is intra-arterial angiography, but this is associated with a number of complications including stroke. The noninvasive techniques of duplex ultrasonography and magnetic resonance angiography are suitable screening methods. Emboli from cardiac sources may also be responsible for amaurosis fugax. Electrocardiography should be performed in all cases, particularly to identify atrial fibrillation. Echocardiography should be undertaken in young patients and in any patient with clinical evidence of a potential cardiac source of emboli. In younger patients without carotid or cardiac disease, amaurosis fugax may be due to choroidal or retinal vascular spasm, in which case calcium channel blockers such as slow-release nifedipine, 60 mg/d, appear to be effective. Antiphospholipid syndrome should be excluded.

Similar obscurations of vision, characteristically on exposure to bright light, may occur with poor ocular perfusion due to severe occlusive carotid disease or to aortic dissection. More transient episodes (lasting only a few seconds to 1 minute) affecting both eyes occur in patients with raised intracranial pressure. In all cases of episodic visual loss, early ophthalmologic consultation is advisable.

Alamowitch S et al: The risk and benefit of endarterectomy in women with symptomatic internal carotid artery disease. Stroke 2005;36:27.

RETINAL DISORDERS ASSOCIATED WITH SYSTEMIC DISEASES

Many systemic diseases are associated with retinal manifestations. These include diabetes mellitus, essential hypertension, preeclampsia-eclampsia of pregnancy, blood dyscrasias, and AIDS. The retinal changes caused by these disorders can be easily observed with an ophthalmoscope.

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Diabetic Retinopathy

Diabetic retinopathy is the leading cause of new blindness among adults in the United States aged 20–65 years. It is broadly classified as nonproliferative or proliferative.

Nonproliferative retinopathy shows dilation of veins, microaneurysms, retinal hemorrhages, retinal edema, and hard exudates. A major subgroup includes those patients in whom visual loss develops owing to edema, exudates, or ischemia at the macula (diabetic maculopathy). This is the most common cause of legal blindness in maturity-onset diabetes.

Proliferative retinopathy is characterized by neovascularization, arising from either the optic disk or the major vascular arcades. Vitreous hemorrhage is a common sequela. Proliferation into the vitreous of blood vessels, with their associated fibrous component, leads to tractional retinal detachment. Without treatment, the visual prognosis with proliferative retinopathy is generally much worse than that with nonproliferative retinopathy. Severe proliferative retinopathy is often complicated by maculopathy.

Nonproliferative retinopathy is occasionally present at the time of diagnosis in type 2 diabetes. Treatment includes optimizing control of blood glucose, blood pressure, and serum lipids. Institution of intensive insulin therapy can be associated with temporary exacerbation of retinopathy, with multiple cotton-wool spots. Laser photocoagulation is helpful in the treatment of focal macular edema but may also be used when there is diffuse macular edema, which may also respond to intravitreal injection of corticosteroid. The presence of macular edema can be detected only by stereoscopic examination of the retina or by fluorescein angiography. The level of visual acuity is a poor guide to the presence of treatable maculopathy—hence the need for regular ophthalmologic follow-up.

Proliferative retinopathy must be recognized early and treated by panretinal laser photocoagulation to prevent blindness. Neovascularization is all too often diagnosed only at the time of vitreous hemorrhage. In some patients, a “preproliferative” retinopathy may be identified. Whether panretinal laser photocoagulation should be undertaken at this time can be determined by the degree of retinal ischemia as assessed by fluorescein angiography.

Surgical treatment (vitrectomy) is used either to remove vitreous hemorrhage and thus allow perioperative panretinal laser photocoagulation for the underlying retinal neovascularization, to deal with retinal detachments involving the macula, to manage rapidly progressive proliferative disease, or to treat persistent macular edema.

Patients with diabetes should have yearly ophthalmoscopic examination through dilated pupils. Examination by an ophthalmologist is advisable in type 1 diabetes of more than 5 years' duration; at the time of diagnosis in type 2 diabetes; in early pregnancy, prior to conception in women contemplating pregnancy, and every 4–8 weeks throughout pregnancy; if ocular symptoms develop; or if there are suspicious findings of retinopathy, especially neovascularization or macular exudates. Failure to diagnose diabetic retinopathy by ophthalmoscopic examination is common, particularly if the pupils are not dilated. The severity of diabetic retinopathy can be decreased by control of blood glucose levels, but good diabetic control is more important in preventing the development of retinopathy than in influencing its subsequent course. Proliferative diabetic retinopathy, especially after successful laser treatment, is not a contraindication to treatment with thrombolytic agents, aspirin, or warfarin unless there has been recent vitreous or preretinal hemorrhage.

Centers for Disease Control and Prevention (CDC): Prevalence of visual impairment and selected eye diseases among persons aged 50 years with and without diabetes—United States, 2002. MMWR Morb Mortal Wkly Rep 2004;53:1069.

Colucciello M: Diabetic retinopathy. Control of systemic factors preserves vision. Postgrad Med 2004;116:57.

Massin P et al: Intravitreal triamcinolone acetonide for diabetic diffuse macular edema: preliminary results of a prospective controlled trial. Ophthalmology 2004;111:218.

Matthews DR et al: Risks of progression of retinopathy and vision loss related to tight blood pressure control in type 2 diabetes mellitus: UKPDS 69. Arch Ophthalmol 2004;122:1631.

Sinclair SH et al: The internist's role in managing diabetic retinopathy: screening for early detection. Cleve Clin J Med 2004;71:151.

Sjolie AK et al: Medical management of diabetic retinopathy. Diabet Med 2004;21:666.

Hypertensive Retinochoroidopathy

Systemic hypertension affects both the retinal and choroidal circulations. The clinical manifestations vary according to the degree and rapidity of rise in blood pressure and the underlying state of the ocular circulation. The most florid disease occurs in young patients with abrupt elevations of blood pressure, such as may occur in pheochromocytoma, malignant hypertension, or preeclampsia-eclampsia.

Chronic hypertension accelerates the development of atherosclerosis. The retinal arterioles become more tortuous and narrow and develop abnormal light reflexes (“silver-wiring” and “copper-wiring”). There is increased venous compression at the retinal arteriovenous crossings (“arteriovenous nicking”), an important factor predisposing to branch retinal vein occlusions. Flame-shaped hemorrhages occur in the nerve fiber layer of the retina.

Acute elevations of blood pressure result in loss of autoregulation in the retinal circulation, leading to the breakdown of endothelial integrity and occlusion of precapillary arterioles and capillaries. These pathologic changes are manifested as cotton-wool spots, retinal hemorrhages, retinal edema, and retinal exudates, often in a stellate appearance at the macula. In the choroid, vasoconstriction and ischemia result in serous retinal detachments

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and retinal pigment epithelial infarcts. These infarcts later develop into pigmented lesions that may be focal, linear, or wedge-shaped. The abnormalities in the choroidal circulation may also affect the optic nerve head, producing ischemic optic neuropathy with optic disk swelling. Malignant hypertensive retinopathy was the term previously used to describe the constellation of clinical signs resulting from the combination of abnormalities in the retinal, choroidal, and optic disk circulation. When there is such severe disease, there is likely to be permanent retinal, choroidal, or optic nerve damage. Precipitous reduction of blood pressure may exacerbate such damage.

Luo BP et al: Update on the ocular manifestations of systemic arterial hypertension. Curr Opin Ophthalmol 2004;15:203.

Wong TY et al: Hypertensive retinopathy. N Engl J Med 2004;351:2310.

Blood Dyscrasias

In conditions characterized by thrombocytopenia or severe anemia, various types of hemorrhages occur in both the retina and choroid and may lead to visual loss. If macular hemorrhages have not occurred, it is possible to regain normal vision with treatment.

Proliferative retinopathy (sickle cell retinopathy) is particularly common in hemoglobin SC disease but may also occur with other hemoglobin S variants. Severe visual loss is rare. Retinal photocoagulation reduces the frequency of vitreous hemorrhage. Surgery is occasionally needed for unresolving vitreous hemorrhage or tractional retinal detachment.

AIDS

Cotton-wool spots, retinal hemorrhages, and microaneurysms are the most common ophthalmic abnormalities in AIDS patients.

Cytomegalovirus (CMV) retinitis occurs when CD4 counts are below 50/mcL. It is characterized by progressively enlarging yellowish-white patches of retinal opacification, which are accompanied by retinal hemorrhages; they usually begin adjacent to the major retinal vascular arcades. Patients are often asymptomatic until there is involvement of the fovea or optic nerve or until retinal detachment develops.

The commonly used agents are intravenous or intravitreal ganciclovir, foscarnet, and cidofovir, which has the significant advantage of a prolonged intracellular half-life such that no more than weekly administration is required. Major side effects are neutropenia with systemic ganciclovir and nephrotoxicity with foscarnet and cidofovir. Dosage of both ganciclovir and foscarnet is adjusted in renal failure. Oral probenecid and intravenous hydration are used to minimize nephrotoxicity from cidofovir. Oral valganciclovir and intravitreal fomivirsen are also effective. All the available agents are virostatic.

Initial therapy is as follows: (1) intravenous—ganciclovir 5 mg/kg twice a day, foscarnet 60 mg/kg three times a day, or cidofovir 5 mg/kg once weekly, usually for 2 weeks; (2) oral—valganciclovir 900 mg twice daily; or (3) by local administration, using either intravitreal injection of ganciclovir, foscarnet, or fomivirsen or the sustained-release ganciclovir intravitreal implant. Intravitreal cidofovir is effective, but there is a high incidence of uveitis, low intraocular pressure, and ciliary body necrosis. Maintenance therapy can be conducted with lower-dose intravenous therapy (ganciclovir 3.75 mg/kg/d or foscarnet 60 mg/kg/d for 5 days each week, or cidofovir 5 mg/ kg once every 2 weeks), with oral ganciclovir (3 g/d) or oral valganciclovir 900 mg once daily, or with intravitreal therapy. Local therapy tends to be more effective than systemic therapy and avoids systemic side effects, but there is a risk of intraocular complications, and the incidence of retinitis in the fellow eye and of extraocular CMV infection is higher. Unresponsive disease or reactivation during maintenance therapy can be managed by changing to a different agent or by use of combination therapy. Retinal detachment, either due to retinitis or as a complication of intravitreal therapy, requires vitrectomy and intravitreal silicone oil. Oral ganciclovir as prophylaxis against cytomegalovirus retinitis in patients with low CD4 counts or high CMV burdens has not been found to be worthwhile.

Antiretroviral therapy may result in reduction of HIV virus load and increase in CD4 counts, and even regression of CMV retinitis without the use of anticytomegalovirus therapy. If the CD4 count is maintained above 100/mcL, it may be possible to discontinue maintenance anticytomegalovirus therapy. Highly active antiretroviral therapy (HAART) occasionally leads to “immune recovery” uveitis, which may lead to visual loss.

Other opportunistic ophthalmic infections occurring in AIDS patients include herpes simplex retinitis, toxoplasmic and candidal chorioretinitis, and herpes zoster ophthalmicus. Kaposi's sarcoma of the conjunctiva and orbital lymphoma may also be seen on rare occasions.

Dunn JP et al: Complications of ganciclovir implant surgery in patients with cytomegalovirus retinitis: the Ganciclovir Cidofovir Cytomegalovirus Retinitis Trial. Retina 2004;24: 41.

Hodge WG et al: Clinical risk factors for cytomegalovirus retinitis in patients with AIDS. Ophthalmology 2004;111: 1326.

Jabs DA et al: Course of cytomegalovirus retinitis in the era of highly active antiretroviral therapy: 1. Retinitis progression. Ophthalmology 2004;111:2224.

Jabs DA et al: Course of cytomegalovirus retinitis in the era of highly active antiretroviral therapy: 2. Second eye involvement and retinal detachment. Ophthalmology 2004;111:2232.

Vrabec TR: Posterior segment manifestations of HIV/AIDS. Surv Ophthalmol 2004;49:131.

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ANTERIOR ISCHEMIC OPTIC NEUROPATHY

Anterior ischemic optic neuropathy—due to inadequate perfusion of the posterior ciliary arteries that supply the anterior portion of the optic nerve—produces sudden visual loss, usually with an altitudinal field defect, and optic disk swelling. In older patients, it is often caused by giant cell arteritis, which necessitates high-dose systemic steroid treatment to prevent visual loss in the fellow eye. (See Central and Branch Retinal Artery Occlusions, above.) The predominant factor predisposing to nonarteritic anterior ischemic optic neuropathy is congenitally small optic disks. Other causative factors include systemic hypertension, diabetes, hyperlipidemia, systemic vasculitis, inherited or acquired thrombophilia, and ingestion of sildenafil.

Rucker JC et al:. Ischemic optic neuropathies. Curr Opin Neurol 2004;17:27.

OPTIC NEURITIS

Optic neuritis is characterized by unilateral loss of vision, which usually develops over a few days. Vision ranges from 20/30 to no perception of light. Commonly there is pain in the region of the eye, particularly on eye movements. Field loss is usually a central scotoma, but a wide range of monocular field defects is possible. There is marked loss of color vision and a relative afferent pupillary defect. In about two-thirds of cases, the optic nerve is normal during the acute stage (retrobulbar optic neuritis). In the remainder, the optic disk is swollen (papillitis) with occasional flame-shaped peripapillary hemorrhages. Visual acuity usually improves within 2–3 weeks and returns to 6/ 12 or better in 95% of previously unaffected eyes. Optic atrophy subsequently develops if there has been destruction of sufficient optic nerve fibers.

Optic neuritis is strongly associated with demyelinating disease, particularly multiple sclerosis. Among patients with clinically isolated optic neuritis, about 40% will develop multiple sclerosis within 10 years but the visual and neurologic prognosis is good. The major risk factors are female gender, multiple white matter lesions on brain magnetic resonance imaging (MRI), and cerebrospinal fluid oligoclonal bands.

In acute demyelinating optic neuritis, intravenous methylprednisolone therapy accelerates visual recovery. Use in an individual patient is determined by the degree of visual loss, the state of the fellow eye, and the patient's visual requirements. In patients with a first episode of optic neuritis and multiple cerebral white matter lesions, long-term interferon therapy reduces the risk of subsequent development of multiple sclerosis by 25% at 2–3 years.

Optic neuritis also occurs with viral infections (including measles, mumps, influenza, and those caused by the varicella-zoster virus), with various autoimmune disorders, particularly systemic lupus erythematosus, and by spread of inflammation from meninges, orbital tissues, or paranasal sinuses. Optic neuritis due to herpes zoster or systemic lupus erythematosus generally has a poorer prognosis and requires high-dose intravenous corticosteroid therapy.

All patients with optic neuritis should be referred urgently for neuro-ophthalmologic assessment. Any patient with isolated optic neuritis in which visual recovery does not occur requires exclusion of a compressive lesion or an intrinsic optic nerve tumor.

Beck RW et al: Neurologic impairment 10 years after optic neuritis. Arch Neurol 2004;61:1386.

Beck RW et al: Visual function more than 10 years after optic neuritis: experience of the optic neuritis treatment trial. Am J Ophthalmol 2004;137:77.

Pirko I et al: The natural history of recurrent optic neuritis. Arch Neurol 2004;61:1401.

OPTIC DISK SWELLING

Optic disk swelling may result from intraocular disease, orbital and optic nerve lesions, severe hypertensive retinochoroidopathy, or raised intracranial pressure. Intraocular causes include central retinal vein occlusion, posterior uveitis, and posterior scleritis. Optic nerve lesions causing disk swelling include optic neuritis; anterior ischemic optic neuropathy; optic disk drusen (pseudopapilledema); optic nerve sheath meningioma; and nerve infiltration by sarcoidosis, leukemia, or lymphoma. Any orbital lesion causing nerve compression may produce disk swelling.

Papilledema (optic disk swelling due to raised intracranial pressure) is usually bilateral and most commonly produces enlargement of the blind spot without loss of acuity. Chronic papilledema, as in idiopathic intracranial hypertension and dural venous sinus occlusion, may be associated with progressive visual field loss and occasionally with profound loss of acuity. All patients with chronic papilledema must be monitored carefully—especially their visual fields—and optic nerve sheath fenestration or lumboperitoneal shunt is considered in those with progressive visual failure not controlled by medical therapy (weight loss where appropriate and acetazolamide).

Optic disk drusen are a possibility when disk swelling is not associated with any visual disturbance or symptoms of raised intracranial pressure. Exposed optic disk drusen may be obvious clinically or can be demonstrated by their autofluorescence. Buried drusen are best detected by orbital ultrasound or computed tomographic (CT) scanning. Other family members may be similarly affected.

Friedman DI et al: Idiopathic intracranial hypertension. J Neuroophthalmol 2004;24:138.

Wilkins JM et al: Visual manifestations of visible and buried optic disc drusen. J Neuroophthalmol 2004;24:125.

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OCULAR MOTOR PALSIES

In complete third nerve paralysis, there is ptosis with a divergent and slightly depressed eye. Extraocular movements are restricted in all directions except laterally (preserved lateral rectus function). Intact fourth nerve (superior oblique) function is detected by the presence of inward rotation on attempted depression of the eye.

Pupillary involvement (dilated pupil that does not react to accommodation or to light shone in either eye) is an important sign differentiating “surgical” from “medical” causes of isolated third nerve palsy. Compressive lesions of the third nerve—eg, aneurysm of the posterior communicating artery and uncal herniation due to a supratentorial mass lesion—characteristically have pupillary involvement. Patients with painful isolated third nerve palsy and pupillary involvement are assumed to have a posterior communicating artery aneurysm until this has been excluded. Medical causes of isolated third nerve palsy include diabetes, hypertension, and giant cell arteritis.

Fourth nerve paralysis causes upward deviation of the eye with failure of depression on adduction. There is vertical diplopia that becomes most apparent on attempted reading and descending stairs. Many cases of isolated fourth nerve palsy are due to a congenital lesion. Trauma is a major cause of acquired—particularly bilateral—fourth nerve palsy, but cerebral neoplasms and medical causes such as in third nerve palsies should also be considered.

Sixth nerve paralysis causes convergent squint in the primary position with failure of abduction of the affected eye, producing horizontal diplopia that increases on gaze to the affected side and on looking into the distance. It is an important sign of raised intracranial pressure. Sixth nerve palsy may also be due to trauma, neoplasms, brain stem lesions, or medical causes.

An intracranial or intraorbital mass lesion should be considered in any patient with an isolated ocular motor palsy. In patients with isolated ocular motor nerve palsies presumed to be due to medical causes, brain MRI is generally only necessary if recovery has not begun within 3 months, although a recent study suggests that it should be undertaken in all cases.

Ocular motor nerve palsies occurring in association with other neurologic signs may be due to lesions in the brain stem, the cavernous sinus, or in the orbit. Lesions around the cavernous sinus involve the upper divisions of the trigeminal nerve, the ocular motor nerves, and occasionally the optic chiasm. Orbital apex lesions involve the optic nerve and the ocular motor nerves.

Myasthenia and dysthyroid eye disease must always be considered in the differential diagnosis of disordered extraocular movements.

Chou KL et al: Acute ocular motor mononeuropathies: prospective study of the roles of neuroimaging and clinical assessment. J Neurol Sci 2004;219:35.

Patel SV et al: Incidence, associations, and evaluation of sixth nerve palsy using a population-based method. Ophthalmology 2004;111:369.

DYSTHYROID EYE DISEASE

Dysthyroid eye disease is a clinical syndrome caused by deposition of mucopolysaccharides and infiltration with chronic inflammatory cells of the orbital tissues, particularly the extraocular muscles. Patients may have clinical or laboratory evidence of thyroid dysfunction, elevated thyroid autoantibodies, or no detectable abnormality outside the orbit. Radioiodine therapy and cigarette smoking increase its severity.

The primary clinical features are proptosis, lid retraction and lid lag, conjunctival chemosis and episcleral inflammation, and extraocular muscle abnormalities due to restriction of their actions. Resulting symptoms are cosmetic abnormalities, surface irritation, which usually responds to artificial tears, and diplopia, which should be treated conservatively (eg, with prisms) in the active stages of the disease and only by surgery when the disease has been static for at least 6 months.

The important complications are corneal exposure and optic nerve compression, both of which may lead to marked visual loss. Treatment is by urgent orbital decompression, either medically, with high-dose systemic steroids (prednisolone 80–100 mg/d)—although this is often of only short-term benefit—by radiotherapy, or by surgery, usually consisting of extensive removal of bone from the medial, inferior, and lateral walls of the orbit.

The optimal management of moderately severe dysthyroid eye disease without visual loss is controversial. Systemic steroids and radiotherapy do not provide definite long-term benefit. Peribulbar steroid injections have been advocated. Surgical decompression may be justified in patients with marked proptosis. Lateral tarsorrhaphy may be used for moderately severe corneal exposure. Other procedures are particularly useful for correcting lid retraction but should not be undertaken until the orbital disease is quiescent and orbital decompression or extraocular muscle surgery has been undertaken. Establishing and maintaining euthyroidism are important in all cases.

Ebner R et al: Treatment of thyroid associated ophthalmopathy with periocular injections of triamcinolone. Br J Ophthalmol 2004;88:1380.

Kim JM et al: The relation of Graves' ophthalmopathy to circulating thyroid hormone status. Br J Ophthalmol 2004;88:72.

ORBITAL CELLULITIS

Orbital cellulitis is manifested by an abrupt onset of fever, proptosis, restriction of extraocular movements, and swelling with redness of the lids. Infection of the paranasal sinuses is the usual underlying cause. Immediate treatment with intravenous antibiotics is necessary to prevent optic nerve damage and spread of infection to the cavernous sinuses, meninges, and brain. The response to antibiotics is usually excellent, but abscess formation may necessitate surgical drainage. In immunocompromised patients, zygomycosis must be considered.

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Greenberg RN et al: Zygomycosis (mucormycosis): emerging clinical importance and new treatments. Curr Opin Infect Dis 2004;17:517.

Howe L et al: Guidelines for the management of periorbital cellulitis/ abscess. Clin Otolaryngol 2004;29:725.

OCULAR TRAUMA

Conjunctival & Corneal Foreign Bodies

If a patient complains of “something in my eye” and gives a consistent history, a foreign body is usually present on the cornea or under the upper lid even though it may not be visible. Visual acuity should be tested before treatment is instituted, as a basis for comparison in the event of complications.

After a local anesthetic (eg, proparacaine, 0.5%) is instilled, the eye is examined with a hand flashlight, using oblique illumination, and loupe. Corneal foreign bodies may be made more apparent by the instillation of sterile fluorescein. They are then removed with a sterile wet cotton-tipped applicator. Polymyxin-bacitracin ophthalmic ointment should be instilled. It is not necessary to patch the eye, but the patient must be examined 24 hours later for secondary infection of the crater. If a corneal foreign body cannot be removed in this manner, the patient should be referred to an ophthalmologist.

Steel foreign bodies usually leave a diffuse rust ring. This requires excision of the affected tissue and is best done under local anesthesia using a slitlamp. Caution: Anesthetic drops should not be given to the patient for self-administration.

If there is no infection, a layer of corneal epithelial cells will line the crater within 24 hours. The intact corneal epithelium forms an effective barrier to infection, but once it is disturbed the cornea becomes extremely susceptible to infection. Early infection is manifested by a white necrotic area around the crater and a small amount of gray exudate. These patients are referred immediately to an ophthalmologist; untreated corneal infection may lead to loss of the eye.

In the case of a foreign body under the upper lid, a local anesthetic is instilled and the lid is everted by grasping the lashes gently and exerting pressure on the mid portion of the outer surface of the upper lid with an applicator. If a foreign body is present, it can easily be removed by passing a wet sterile cotton-tipped applicator across the conjunctival surface.

Intraocular Foreign Body

Intraocular foreign body requires emergency treatment by an ophthalmologist. Patients giving a history of “something hitting the eye”—particularly while hammering on metal or using grinding equipment—must be assessed for this possibility, especially when no corneal foreign body is seen, a corneal or scleral wound is apparent, or there is marked visual loss or media opacity. Such patients must be treated as for corneal laceration (see below) and referred without delay. Intraocular foreign bodies significantly increase the risk of intraocular infection.

Corneal Abrasions

A patient with a corneal abrasion complains of severe pain and photophobia. There is often a history of trauma to the eye, commonly involving a fingernail, piece of paper, or contact lens. Visual acuity is recorded, and the cornea and conjunctiva are examined with a light and loupe to rule out a foreign body. If an abrasion is suspected but cannot be seen, sterile fluorescein is instilled into the conjunctival sac: the area of corneal abrasion will stain a deeper green than the surrounding cornea.

Treatment includes polymyxin-bacitracin ophthalmic ointment, mydriatic (cyclopentolate 1%), and analgesics either topical or oral nonsteroidal anti-inflammatory agents. Padding the eye is probably not helpful. The patient should be reviewed within 48 hours to be certain the cornea has healed. Recurrent corneal erosion may follow corneal abrasions.

Wilson SA et al: Management of corneal abrasions. Am Fam Physician 2004;70:123.

Contusions

Contusion injuries of the eye and surrounding structures may cause ecchymosis (“black eye”), subconjunctival hemorrhage, edema or rupture of the cornea, hemorrhage into the anterior chamber (hyphema), rupture of the root of the iris (iridodialysis), paralysis of the pupillary sphincter, paralysis of the muscles of accommodation, cataract, dislocation of the lens, vitreous hemorrhage, retinal hemorrhage and edema (most common in the macular area), detachment of the retina, rupture of the choroid, fracture of the orbital floor (“blowout fracture”), or optic nerve injury. Many of these injuries are immediately obvious; others may not become apparent for days or weeks. Patients with moderate to severe contusions should be seen by an ophthalmologist.

Any injury causing hyphema involves the danger of secondary hemorrhage, which may cause intractable glaucoma with permanent visual loss. The patient should be advised to rest until complete resolution has occurred. Daily ophthalmologic assessment is essential. Aspirin and any drugs inhibiting coagulation increase the risk of secondary hemorrhage and are to be avoided. Sickle cell anemia or trait adversely affects outcome.

Lacerations

A. LIDS

If the lid margin is lacerated, the patient should be referred for specialized care, since permanent notching may result. Lacerations of the lower eyelid near the inner canthus often sever the lower canaliculus. Lid lacerations not involving the margin may be sutured like any skin laceration.

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B. CONJUNCTIVA

In lacerations of the conjunctiva, sutures are not necessary. To prevent infection, sulfonamides or other antibiotics are instilled into the eye until the laceration is healed.

C. CORNEA OR SCLERA

Patients with suspected corneal or scleral lacerations must be seen promptly by an ophthalmologist. Manipulation is kept to a minimum, since pressure may result in extrusion of the intraocular contents. The eye is bandaged lightly and covered with a metal shield that rests on the orbital bones above and below. The patient should be instructed not to squeeze the eye shut and to remain still. The eye is routinely studied by x-ray, and CT scanning if necessary, to identify and localize any metallic intraocular foreign body. MRI is contraindicated owing to the risk of movement of the foreign body in the magnetic field. Endophthalmitis occurs in over 5% of open globe injuries.

Essex RW et al: Post-traumatic endophthalmitis. Ophthalmology 2004;111:2015.

ULTRAVIOLET KERATITIS (ACTINIC KERATITIS)

Ultraviolet burns of the cornea are usually caused by use of a sunlamp without eye protection, exposure to a welding arc, or exposure to the sun when skiing (“snow blindness”). There are no immediate symptoms, but about 6–12 hours later the patient complains of agonizing pain and severe photophobia. Slitlamp examination after instillation of sterile fluorescein shows diffuse punctate staining of both corneas.

Treatment consists of binocular patching and instillation of 1–2 drops of 1% cyclopentolate (to relieve the discomfort of ciliary spasm). All patients recover within 24–48 hours without complications. Local anesthetics should not be prescribed.

Chemical Conjunctivitis & Keratitis

Chemical burns are treated by irrigation of the eyes with saline solution or plain water as soon as possible after exposure. Neutralization of an acid with an alkali or vice versa generates heat and may cause further damage. Alkali injuries are more serious and require prolonged irrigation, since alkalies are not precipitated by the proteins of the eye as are acids. It is important to remove any retained particulate matter such as is typically present in injuries involving cement and building plaster. This may require double eversion of the upper lid. The pupil should be dilated with 1% cyclopentolate, 1 drop twice a day, to relieve discomfort and prophylactic topical antibiotics should be started. In moderate to severe injuries, intensive topical corticosteroids and topical and systemic vitamin C are also necessary. Complications include mucus deficiency, scarring of the cornea and conjunctiva, symblepharon (adhesions between the tarsal and bulbar conjunctiva), tear duct obstruction, and secondary infection. It can be difficult to assess severity of chemical burns without slit-lamp examination.

PRINCIPLES OF TREATMENT OF OCULAR INFECTIONS

Before determining the drug of choice for treatment of ocular infection, the causative organisms must be identified, but in most cases empirical treatment is used in the first instance. In the treatment of conjunctivitis and for prophylaxis against ocular infection, it is preferable to use a drug that is not given systemically. Although fluoroquinolones, including the fourth-generation fluoroquinolones, are advocated for the treatment of conjunctivitis, they should be reserved for treatment of bacterial keratitis and other serious infections. Of the available local antibacterial agents, the sulfonamides are effective and inexpensive; sulfisoxazole and sodium sulfacetamide are examples. The sulfonamides have the added advantages of low allergenicity and effectiveness against the chlamydial group of organisms. They are available in ointment or solution form. Combined bacitracin-polymyxin ointment is often used prophylactically after corneal foreign body removal for the protection it affords against both grampositive and gram-negative organisms.

Among the most effective broad-spectrum antibiotics for ophthalmic use are fluoroquinolones (ciprofloxacin, ofloxacin, norfloxacin, levofloxacin, moxifloxacin, and gatifloxacin), gentamicin, tobramycin, and neomycin. For pneumococcus, one of the newer fluoroquinolones, penicillin G, or nafcillin (if β-lactamase resistance is present) is required. Allergic reactions to neomycin are common. Other antibiotics frequently used are erythromycin, the tetracyclines, and the cephalosporins.

Method of Administration

Most ocular anti-infective drugs are administered locally. Ointments have greater therapeutic effectiveness than solutions, since contact can be maintained longer. However, they do cause blurring of vision; if this must be avoided, solutions should be used.

Systemic administration is required for all intraocular infections, orbital cellulitis, dacryocystitis, gonococcal keratoconjunctivitis, inclusion conjunctivitis, and severe external infection that does not respond to local treatment.

Kowalski RP et al: Infectious disease: changing antibiotic susceptibility. Ophthalmol Clin North Am 2003;16:1.

TECHNIQUES USED IN THE TREATMENT OF OCULAR DISORDERS

Table 7-2 lists commonly used ophthalmic drugs and their indications and costs.

Table 7-2. Topical ophthalmic agents.

Agent	Representative Cost/Size¹	Sig	Indications
AGENTS FOR GLAUCOMA AND OCULAR HYPERTENSION
Sympathomimetics
Apraclonidine HCl 0.5% solution (Iopidine)	$66.48/5 mL	1 drop three times daily	Reduction of intraocular pressure. Expensive. Reserve for treatment of resistant cases.
Apraclonidine HCl 1% solution (Iopidine)	$11.03/unit dose 0.1 mL	1 drop 1 hour before and immediately after anterior segment laser surgery	To control or prevent elevations of intraocular pressure after laser trabeculoplasty or iridotomy.
Brimonidine tartrate 0.2% solution (Alphagan)	$32.65/5 mL	1 drop two or three times daily	Reduction of intraocular pressure.
Dipivefrin HCl 0.1% solution (Propine)²	$14.07/5 mL	1 drop every 12 hours	Open-angle glaucoma.
Epinephrine HCl 0.25%, 0.5% (Epifrin), 1%, and 2% solution (various)³	1%:$49.69/15 mL 2%:$54.36/15 mL	1 drop twice daily
β-Adrenergic blocking agents
Betaxolol HCl 0.5% solution and 0.25% suspension (Betoptic S)⁴	0.5%:$44.56/10 mL 0.25%:$78.24/10 mL	1 drop twice daily	Reduction of intraocular pressure.
Carteolol HCl 1% solution (Ocupress)⁵	$37.07/10 mL	1 drop twice daily
Levobunolol HCl 0.25% and 0.5% solution (Betagan)⁵	0.5%:$32.25/10 mL	1 drop once or twice daily
Metipranolol HCl 0.3% solution (OptiPranolol)⁵	$26.85/10 mL	1 drop twice daily
Timolol 0.25% and 0.5% solution (Betimol)⁵	0.5%:$42.84/10 mL	1 drop once or twice daily
Timolol maleate 0.25% and 0.5% solution (Timoptic) and 0.25% and 0.5% gel (Timoptic-XE)⁵	0.5% solution:$32.29/10 mL 0.5% gel:$32.30/5 mL	1 drop once or twice daily
Miotics
Pilocarpine HCl (various)⁶ 1–4%, 6%, 8%, and 10%	2%:$11.80/15 mL	1 drop three or four times daily	Reduction of intraocular pressure, treatment of acute or chronic angle-closure glaucoma, and pupillary constriction.
Pilocarpine HCl 4% gel (Pilopine HS)	$42.00/4 g	Apply 0.5-inch ribbon in lower conjunctival sac at bedtime
Carbonic anhydrase inhibitors
Dorzolamide HCl 2% solution (Trusopt)	$55.88/10 mL	1 drop three times daily	Reduction of intraocular pressure.
Brinzolamide 1% suspension (Azopt)	$67.80/10 mL	1 drop three times daily	Reduction of intraocular pressure.
Prostaglandin analogs
Bimatoprost 0.03% solution(Lumigan)	$66.45/2.5 mL	1 drop once daily at night
Latanoprost 0.005% solution (Xalatan)	$58.84/2.5 mL	1 drop once or twice daily at night
Travoprost 0.004% solution (Travatan)	$59.70/2.5 mL	1 drop once daily at night	Reduction of intraocular pressure.
Unoprostone 0.15% solution (Rescula)	$51.50/5 mL	1 drop twice daily	Reduction of intraocular pressure.
Combined preparations
Xalacom (latanoprost 0.005% and timolol 0.5%)	Not available in the United States	1 drop daily in the morning	Reduction of intraocular pressure.
Cosopt (dorzolamide 2% and timolol 0.5%)	$53.51/5 mL	1 drop twice daily	Reduction of intraocular pressure.
ANTI-INFLAMMATORY AGENTS
Nonsteroidal anti-inflammatory agents⁷
Diclofenac sodium 0.1% solution (Voltaren)	$67.61/5 mL	1 drop to operated eye four times daily beginning 24 hours after cataract surgery and continuing through first 2 postoperative weeks	Treatment of postoperative inflammation following cataract extraction and laser corneal surgery.
Flurbiprofen sodium 0.03% solution (various)	$8.73/2.5 mL	1 drop every half hour beginning 2 hours before surgery; 1 drop to operated eye four times daily beginning 24 hours after cataract surgery	Inhibition of intraoperative miosis. Treatment of cystoid macular edema and inflammation after cataract surgery.
Ketorolac tromethamine 0.5% solution (Acular)	$71.53/5 mL	1 drop four times daily	Relief of ocular itching due to seasonal allergic conjunctivitis.
Corticosteroids⁸
Dexamethasone sodium phosphate 0.1% solution (various)	$17.31/5 mL	1 or 2 drops as often as indicated by severity; use every hour during the day and every 2 hours during the night in severe inflammation; taper off as inflammation decreases	Treatment of steroid-responsive inflammatory conditions of anterior segment.
Dexamethasone sodium phosphate 0.05% ointment (various)	$6.34/3.5 g	Apply thin coating on lower conjunctival sac three or four times daily
Fluorometholone 0.1% suspension (various)⁹	$26.16/10 mL	1 or 2 drops as often as indicated by severity; use every hour during the day and very 2 hours during the night in severe inflammation; taper off as inflammation decreases
Fluorometholone 0.25% suspension (FML Forte)⁹	$37.60/10 mL
Fluorometholone 0.1% ointment (FML S.O.P.)	$34.00/3.5 g	Apply thin coating on lower conjunctival sac three or four times daily
Medrysone 1% suspension (HMS)	$33.24/10 mL	1 or 2 drops as often as indicated by severity of inflammation; use every hour during the day and every 2 hours during the night in severe inflammation; taper off as inflammation decreases
Prednisolone acetate 0.12% suspension (Pred Mild)	$36.14/10 mL
Prednisolone acetate 0.125% suspension (various)	$36.96/10 mL
Prednisolone sodium phosphate 0.125% solution (various)	$27.29/10 mL
Prednisolone acetate 1% suspension (various)	$23.10/10 mL	1 or 2 drops as often as indicated by severity of inflammation; use every hour during the day and every 2 hours during the night in severe inflammation; taper off as inflammation decreases	Treatment of steroid-responsive inflammatory conditions of anterior segment.
Prednisolone sodium phosphate 1% solution (various)	$24.06/10 mL
Rimexolone 1% suspension (Vexol)	$49.32/10 mL
Mast cell stabilizers
Cromolyn sodium 4% solution (Crolom)	$37.20/10 mL	1 drop four to six times daily	Allergic conjunctivitis.
Ketotifen fumarate 0.025% solution (Zaditor)	$66.80/5 mL	1 drop two to four times daily	Allergic conjunctivitis.
Lodoxamide tromethamine 0.1% solution (Alomide)	$69.12/10 mL	1 or 2 drops four times daily (up to 3 months)	Allergic conjunctivitis and vernal keratoconjunctivitis.
Nedocromil sodium 2% solution (Alocril)	$79.85/5 mL	1 drop twice daily	Allergic conjunctivitis.
Olopatadine hydrochloride 0.1% solution (Patanol)	$74.16/5 mL	1 drop twice daily	Allergic conjunctivitis.
ANTIBIOTIC OINTMENTS AND SOLUTIONS
Bacitracin 500 units/g ointment (various)¹⁰	$4.75/3.5 g	Refer to package insert (instructions vary)	Infections involving lid, conjunctiva, or cornea.
Chloramphenicol 1% (10 mg/g) ointment (Ocu-chlor)¹¹	$1.65/3.5 g		As above, with both gram-positive and gram-negative coverage.
Ciprofloxacin HCl (Ciloxan)	0.3% solution: $50.46/5 mL 0.3% ointment: $50.46/3.5 g
Erythromycin 0.5% ointment (various)¹²	$5.62/3.5 g
Gatifloxacin 0.3% solution (Zymar)	$56.42/5 mL
Gentamicin sulfate 0.3% solution (various)	$8.17/5 mL
Gentamicin sulfate 0.3% ointment (various)	$19.67/3.5 g
Moxifloxacin sulfate 0.5% solution (Vigamox)	$51.24/3 mL
Norfloxacin 0.3% solution (Chibroxin)	Not available in the United States
Ofloxacin 0.3% solution (Ocuflox)	$50.81/5 mL
Polymyxin B sulfate 500,000 units, powder for solution (Polymyxin B Sulfate Sterile)¹³	$12.60/500,000 units
Tobramycin 0.3% solution (various) Tobramycin 0.3% ointment (Tobrex)	$15.00/5 mL $53.88/3.5 g	Refer to package insert (instructions vary)	As above, with both gram-positive and gram-negative coverage.
Sulfacetamide sodium 10% solution (various)	$5.08/15 mL	1 or 2 drops every 1–3 hours	Conjunctivitis, corneal ulcer, and other superficial ocular infections due to susceptible microorganisms.
Sulfacetamide sodium 10% ointment (various)	$8.10/3.5 g	Apply small amount (0.5 inch) into lower conjunctivitis sac once to four times daily and at bedtime	Conjunctivitis, corneal ulcer, and other superficial ocular infections due to susceptible microorganisms.
Note: Many combination products containing antibiotics, antibiotics and steroids, or sulfonamides and steroids are available as solutions, suspensions, or ointments.
TOPICAL ANTIFUNGAL AGENTS
Natamycin 5% suspension (Natacyn)	$147.36/15 mL	1 drop every 1–2 hours	Fungal blepharitis, conjunctivitis, and keratitis caused by susceptible organisms. Drug of choice for Fusarium solani keratitis.
TOPICAL ANTIVIRAL AGENTS
Ganciclovir 4.5 mg surgical insert (Vitrasert)	$5000.00 each	1 implant every 5–8 months	Treatment of cytomegalovirus retinitis in patients with AIDS.
Trifluridine 1% solution (Viroptic)	$104.95/7.5 mL	1 drop onto cornea every 2 hours while awake for a maximum daily dose of 9 drops until resolution occurs; then an additional 7 days of 1 drop every 4 hours while awake (minimum five times daily)	Primary keratoconjunctivitis and recurrent epithelial keratitis due to herpes simplex virus types 1 or 2.¹⁴
TOPICAL ANTIHISTAMINICS¹⁵
Levocabastine HCl 0.05% ophthalmic solution (Livostin)	$81.29/10 mL	1 drop four times daily (up to 2 weeks)	Allergic conjunctivitis; temporary relief of seasonal allergic conjunctivitis.
Emedastine difumarate 0.05% solution (Emadine)	$54.60/5 mL	1 drop four times daily	Allergic conjunctivitis.
¹Average wholesale price (AWP, for AB-rated generic when available) for quantity listed. Source: Red Book, Update, Vol. 24, April 2005. AWP may not accurately represent the actual pharmacy cost because wide contractual variations exist among institutions. ²Macular edema occurs in 30% of patients. ³May (rarely) increase blood pressure. Caution: Avoid in patients with sulfite hypersensitivity (some brands contain sulfite). ⁴Cardioselective (β1) β-blocker. Nonselective (^β1 and ^β2) ^β-blocker. Monitor all patients for systemic side effects, particularly exacerbation of asthma. ⁶Decreased night vision, headaches possible. ⁷Cross-sensitivity to aspirin and other nonsteroidal anti-inflammatory drugs. ⁸Long-term use may increase intraocular pressure or cause cataracts. ⁹May be less likely to elevate intraocular pressure. ¹⁰Little efficacy against gram-negative organisms (except Neisseria). ¹¹Aplastic anemia has been reported with prolonged ophthalmic use. Use only in serious infections for which less toxic drugs are ineffective or contraindicated. ¹²Also indicated for prophylaxis of ophthalmia neonatorum due to N gonorrhoeae or C trachomatis. Increasing resistance of S pneumoniae and P aeruginosa has been noted. ¹³No gram-positive coverage. ¹⁴Recurrences are common and call for additional 7-day treatment. ¹⁵Antihistamines (topical) are potential sensitizers and may produce local reactions.

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Instilling Medications

The patient is placed in a chair with head tilted back, both eyes open, and looking up. The lower lid is retracted slightly, and 2 drops of liquid are instilled into the lower cul-de-sac. The patient looks down while finger contact is maintained, so that the eyes are not squeezed shut. Ointments are instilled in the same general manner.

For self-medication, the same techniques are used except that medications are usually better instilled with the patient lying down.

Eye Bandage

Most eye bandages should be applied firmly enough to hold the lid securely against the cornea. An ordinary patch consisting of gauze-covered cotton is usually sufficient. Tape is applied from the cheek to the forehead.

Eyelid Taping

Eyelid taping, such as for corneal protection in facial palsy, is best achieved with 1-inch-width transparent plastic adhesive tape (eg, Transpore or even Sellotape) placed horizontally over the closed eyelids from the side of the nose to the temple.

PRECAUTIONS IN MANAGEMENT OF OCULAR DISORDERS

Use of Local Anesthetics

Unsupervised self-administration of local anesthetics is dangerous because the patient may further injure an anesthetized eye without knowing it. The drug may also interfere with the normal healing process.

Pharmakakis NM et al: Corneal complications following abuse of topical anesthetics. Eur J Ophthalmol 2002;12:373.

Pupillary Dilation

Dilating the pupil can very occasionally precipitate acute glaucoma if the patient has a narrow anterior chamber angle and should be undertaken with caution if the anterior chamber is obviously shallow (readily determined by oblique illumination of the anterior segment of the eye). A short-acting mydriatic such as tropicamide should be used and the patient warned to report immediately if ocular discomfort or redness develops. Angle closure is more likely to occur if pilocarpine is used to overcome pupillary dilation than if the pupil is allowed to constrict naturally.

Corticosteroid Therapy

Repeated use of local corticosteroids presents several hazards: herpes simplex (dendritic) keratitis, fungal infection, open-angle glaucoma, and cataract formation. Furthermore, perforation of the cornea may occur when the corticosteroids are used for herpes simplex keratitis. Topical nonsteroidal anti-inflammatory agents are being used increasingly. The potential for causing or exacerbating systemic hypertension, diabetes mellitus, gastritis, or osteoporosis must always be borne in mind when systemic corticosteroids are prescribed, such as for uveitis or giant cell arteritis.

Garrott HM et al: Glaucoma from topical corticosteroids to the eyelids. Clin Exp Ophthalmol 2004;32:224.

Ross JJ et al: Facial eczema and sight-threatening glaucoma. J R Soc Med 2004;97:485.

Contaminated Eye Medications

Ophthalmic solutions are prepared with the same degree of care as fluids intended for intravenous administration, but once bottles are opened there is always a risk of contamination, particularly with solutions of tetracaine, proparacaine, fluorescein, and any preservative-free preparations. The most dangerous is fluorescein, as this solution is frequently contaminated with P aeruginosa, which can rapidly destroy the eye. Sterile fluorescein filter paper strips are recommended for use in place of fluorescein solutions.

Whether in plastic or glass containers, eye solutions should not remain in use for long periods after the bottle is opened. Four weeks after opening is an absolute maximal time to use a solution containing preservatives before discarding. Preservative-free preparations should be kept refrigerated and discarded within 1 week after opening.

If the eye has been injured accidentally or by surgical trauma, it is of the greatest importance to use freshly opened bottles of sterile medications or singleuse eyedropper units.

Uchio E et al: Adenovirus detected by polymerase chain reaction in multidose eyedrop bottles used by patients with adenoviral keratoconjunctivitis. Am J Ophthalmol 2002;134:618.

Toxic & Hypersensitivity Reactions to Topical Therapy

Patients receiving long-term topical therapy may develop local toxic or hypersensitivity reactions to the active agent or preservatives, especially if there is inadequate tear secretion. Preservatives in contact lens cleaning solutions may produce similar problems. Burning and soreness are exacerbated by drop instillation or contact lens insertion; occasionally, fibrosis and scarring of the conjunctiva and cornea may occur.

An antibiotic instilled into the eye can sensitize the patient to that drug and cause an allergic reaction upon subsequent systemic administration.

Systemic Effects of Ocular Drugs

The systemic absorption of certain topical drugs (through the conjunctival vessels and lacrimal drainage

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system) must be considered when there is a systemic medical contraindication to the use of the drug. Ophthalmic solutions of the nonselective β-blockers, eg, timolol, may worsen patients with congestive heart failure or asthma. Atropine ointment should be prescribed for children rather than the drops, since absorption of the 1% topical solution may be toxic. Phenylephrine eye drops may precipitate hypertensive crises and angina. Also to be considered are adverse interactions between systemically administered and ocular drugs. Using only 1 or 2 drops at a time and a few minutes of nasolacrimal occlusion or eyelid closure ensure maximum efficacy and decrease systemic side effects of topical agents.

Table 7-3. Adverse ocular effects of systemic drugs.

Drug	Possible Side Effects
Respiratory drugs Oxygen Anticholinergic bronchodilators Cetirizine	Retinopathy of prematurity. Angle-closure glaucoma due to mydriasis, blurring of vision due to cycloplegia. Oculogyric crisis.
Cardiovascular system drugs Digitalis Quinidine Thiazides (Diuril, etc) Carbonic anhydrase inhibitors (acetazolamide) Amiodarone	Disturbances of color vision, scotomas, photopsia. Optic neuritis (rare). Xanthopsia (yellow vision), myopia. Ocular hypotony, transient myopia. Corneal deposits, optic neuropathy, thyroid ophthalmopathy.
Gastrointestinal drugs Anticholinergic agents	Risk of angle-closure glaucoma due to mydriasis, blurring of vision due to cycloplegia (occasional).
Central nervous system drugs Barbiturates Chloral hydrate Phenothiazines Amphetamines Monoamine oxidase inhibitors Tricyclic agents Phenytoin Neostigmine Morphine Haloperidol Lithium carbonate Diazepam Topiramate Paroxetine Vigabatrin	Extraocular muscle palsies with diplopia, nystagmus, ptosis, cortical blindness. Diplopia, ptosis, miosis. Deposits of pigment in conjunctiva, cornea, lens, and retina, oculogyric crises. Widening of palpebral fissure, blurring of vision due to mydriasis. Nystagmus, extraocular muscle palsies, optic atrophy. Angle-closure glaucoma due to mydriasis, blurring of vision due to cycloplegia. Nystagmus, diplopia, ptosis, slight blurring of vision (rare). Nystagmus, miosis. Miosis. Capsular cataract. Exophthalmos, oculogyric crisis, nystagmus. Nystagmus. Angle-closure glaucoma. Angle-closure glaucoma. Visual field constriction.
Hormonal agents Corticosteroids	Cataract (posterior subcapsular); local immunologic suppression, causing susceptibility to viral (herpes simplex), bacterial, and fungal infections; steroid-induced glaucoma.
Female sex hormones	Retinal artery occlusion, retinal vein occlusion, papilledema, ocular palsies with diplopia, nystagmus, optic neuropathy.
Tamoxifen	Crystalline retinal deposits.
Antibiotics Chloramphenicol Streptomycin Tetracycline Minocycline	Optic neuropathy. Optic neuropathy. Papilledema, transient myopia. Papilledema.
Antimalarial agents Chloroquine, etc	Retinal degeneration principally involving the macula, keratopathy, ocular palsies, ptosis.
Amebicides Iodochlorhydroxyquin	Optic atrophy.
Chemotherapeutic agents Sulfonamides Ethambutol Isoniazid	Stevens-Johnson syndrome. Optic neuropathy. Optic neuropathy.
Heavy metals Gold salts Lead compounds	Deposits in the cornea and conjunctiva. Optic atrophy, papilledema, ocular palsies.
Chelating agents Penicillamine	Ocular pemphigoid, optic neuritis, ocular myasthenia.
Oral hypoglycemic agents Chlorpropamide	Transient change in refractive error, diplopia, Stevens-Johnson syndrome.
Vitamins Vitamin A Vitamin D	Papilledema, retinal hemorrhages, loss of eyebrows and eyelashes, nystagmus, diplopia, blurring of vision. Band-shaped keratopathy.
Antirheumatic agents Salicylates Indomethacin Phenylbutazone	Nystagmus, retinal hemorrhages, cortical blindness (rare). Corneal deposits. Retinal hemorrhages.
Dermatologic agents Isotretinoin Retinoids (isotretinoin, tretinoin, acitretin, and etretinate)	Blepharoconjunctivitis, corneal opacities, decreased dark adaptation, decreased contact lens tolerance, teratogenic ocular abnormalities. Papilledema.
Bisphosphonates Pamidronate Alendronate	Scleritis, uveitis, conjunctival hyperemia. Scleritis.

Fraunfelder FW et al: Adverse systemic effects from pledgets of topical ocular phenylephrine 10%. Am J Ophthalmol 2002; 134:624.

ADVERSE OCULAR EFFECTS OF SYSTEMIC DRUGS

Systemically administered drugs produce a wide variety of adverse effects on the visual system. Table 7-3 lists the major examples.

Flach AJ, Fraunfelder FW: Ocular and systemic side effects of drugs. In: Vaughan & Asbury's General Ophthalmology, 16th ed. Riordan-Eva P, Whitcher JP (editors). McGraw-Hill, 2004.