Bacterial keratitis
Pathogenesis
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Pathogens: most common are (a) Pseudomonas aeruginosa , (b) S. aureus , and (c) streptococci.
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Risk factors: (a) contact lens wear, (b) trauma, and (c) ocular surface disease.
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Diagnosis
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Presentation: subacute onset of pain, photophobia, blurred vision, and discharge.
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Signs: (a) epithelial defect with larger infiltrate ( Fig. 6.1 ), (b) stromal oedema, (c) anterior uveitis, often with hypopyon ( Fig. 6.2 ), and (d) severe ulceration may lead to descemetocele formation and perforation ( Fig. 6.3 ).
Fig 6.1
Fig 6.2
Fig 6.3
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Differential diagnosis: (a) alternative microorganisms (fungi, acanthamoeba, stromal herpes simplex keratitis, mycobacteria), (b) severe marginal keratitis, and (c) sterile infiltrates associated with contact lens wear.
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Investigations: (a) corneal scraping for microscopy, (b) culture (blood, chocolate, and Sabouraud agar) with antibiotic sensitivity determination, (c) conjunctival swabs, and (d) culture of contact lenses and lens cases.
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Treatment
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Indications for hospital admission: (a) patients unlikely to comply or unable to self-administer treatment, and (b) aggressive disease/only eye.
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Topical antibiotics: instillation at hourly intervals for 24–48 h, and then tapered according to clinical progress; options include (a) monotherapy with a fluoroquinolone (e.g. ciprofloxacin, ofloxacin, moxifloxacin, gatifloxacin); (b) duotherapy (e.g. cefuroxime 5%, gentamicin 1.5%) may be preferred as first-line empirical treatment in aggressive disease or if streptococci suspected; (c) if no improvement is evident after 24–48 hr, the regimen should be reviewed; and (d) if there is still no improvement after a further 48 hr, suspension of treatment should be considered for 24 hr and then re-scraping performed, with investigation for nonbacterial infection (additional stains and culture media). Corneal biopsy for histology and culture may be necessary in difficult cases.
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Topical steroids: may be commenced once clinical improvement is seen, but early discontinuation may lead to recurrence of sterile inflammation.
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Indications for systemic antibiotics: (a) potential for systemic involvement ( N. meningitidis , H. influenzae , N. gonorrhoeae ), (b) severe corneal thinning with threatened perforation (ciprofloxacin for antibacterial activity and a tetracycline for anticollagenase effect), and (c) scleral involvement.
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Surgery: excisional keratoplasty, (penetrating or deep lamellar), may be considered in resistant cases or for incipient or actual perforation.
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Fungal keratitis
Predisposing factors: (a) chronic ocular surface disease, (b) long-term use of topical steroids, often with prior corneal transplantation, (c) contact lens wear, (d) systemic immunosuppression, (e) diabetes, and (f) trauma often involving plant matter or gardening/agricultural tools, (filamentous keratitis).
Diagnosis
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Presentation: gradual onset of pain, grittiness, photophobia, blurred vision, and watery or mucopurulent discharge; diagnosis is often delayed unless there is a high index of suspicion.
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Candida keratitis: (a) yellow-white densely suppurative infiltrate ( Fig. 6.4 ); (b) a collar-stud morphology may be seen.
Fig 6.4
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Filamentous keratitis: (a) grey or yellow-white stromal infiltrate with indistinct fluffy margins, satellite lesions ( Fig. 6.5 ), (b) feathery extensions, and/or (c) ring-shaped infiltrate.
Fig 6.5
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Other features: (a) anterior uveitis, (b) endothelial plaque, (c) scleritis, and (d) sterile or infective endophthalmitis; an epithelial defect is not always present.
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Differential diagnosis: bacterial, herpetic, and acanthamoebal keratitis; co-infection can occur.
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Investigations: (a) scraping for Gram and Giemsa staining (both approximately 50% sensitive), (b) silver stains (more commonly performed on histological sections), (c) culture on Sabouraud agar (most fungi will also grow on blood agar and enrichment media), (d) culture of contact lenses and lens cases, (e) corneal biopsy; (f) confocal microscopy may permit in vivo identification.
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Treatment
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Topical: initially hourly for 48 h and then reduced as signs permit; most antifungals are only fungistatic, so treatment should be continued for at least 12 weeks. Improvement may be slower than in bacterial infection; removal of epithelium over the lesion may enhance drug penetration.
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Candida infection: amphotericin B 0.15% or econazole 1%; alternatives include natamycin 5%, fluconazole 2%, and clotrimazole 1%.
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Filamentous infection: atamycin 5% or econazole 1%; alternatives include amphotericin B 0.15% and miconazole 1%.
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Systemic antifungals: (voriconazole, itraconazole, fluconazole) should be considered in (a) severe cases, (b) lesions near the limbus, or (c) suspected endophthalmitis.
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Other measures: (a) systemic tetracycline for significant thinning, (b) superficial keratectomy can be effective for de-bulking, and (c) therapeutic keratoplasty (penetrating or deep anterior lamellar) when medical therapy is ineffective or following perforation.
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Herpes simplex keratitis
Pathogenesis
Herpes simplex keratitis is the most common infectious cause of corneal blindness in developed countries. Herpes simplex virus (HSV) has two subtypes:
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HSV-1: causes disease principally above the waist.
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HSV-2: causes venereally acquired infection (genital herpes).
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Primary infection: usually occurs subclinically in childhood; subclinical reactivation can occur, during which patients are contagious.
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Clinical reactivation: can occur in response to a variety of stressors (e.g. fever, hormonal change, ultraviolet radiation); the virus replicates and is transported in the sensory axons to the periphery, the pattern of disease depending on the site of reactivation.
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Epithelial (dendritic or geographic) keratitis: caused by active viral replication.
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Disciform keratitis: caused by hypersensitivity reaction to viral antigen.
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Necrotizing stromal keratitis: caused by active viral replication within the stroma, although immune-mediated inflammation plays a significant role.
Epithelial keratitis
Diagnosis
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Presentation: mild discomfort, redness, photophobia, watering, and blurred vision.
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Signs: (a) swollen opaque epithelial cells arranged in a coarse punctate or stellate pattern, (b) formation of a branching ‘dendritic’ ulcer with characteristic terminal buds ( Fig. 6.6 ), and (c) reduced corneal sensation; inadvertent use of topical steroids may promote enlargement of the ulcer to a geographic configuration ( Fig. 6.7 ).
Fig 6.6
Fig 6.7
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Treatment
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Topical antivirals: (aciclovir ointment, ganciclovir gel, trifluridine solution) have approximately equivalent effect, with vidarabine an alternative; most cases resolve within 2 weeks on treatment.
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Debridement: 2 mm beyond the ulcer edge with a sterile cellulose sponge may be used as an adjunct; this protects adjacent epithelium from infection and reduces the antigenic stimulus to inflammation.
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Oral antivirals: (aciclovir, famciclovir, valaciclovir) are an effective alternative to topical therapy, when the latter is poorly tolerated, or in resistant cases; combination of two topical agents with oral valaciclovir or famciclovir may be effective.
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Disciform keratitis
Diagnosis
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Presentation: blurred vision, mild discomfort, and redness.
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Signs: (a) central zone of stromal oedema with overlying epithelial oedema, underlying keratic precipitates, and folds in Descemet membrane ( Fig. 6.8 ), (b) surrounding (Wessely) immune ring of stromal haze ( Fig. 6.9 ), and (c) reduced corneal sensation.
Fig 6.8
Fig 6.9
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Course: consecutive episodes may be associated with gradually worsening scarring and superficial or deep vascularization; mid-stromal scarring can appear as interstitial keratitis.
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Treatment
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Initial: topical steroids (prednisolone 1%, dexamethasone 0.1%) with antiviral cover, both four times daily.
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Subsequent: as improvement occurs, both are tapered. Some patients require a weaker steroid (fluorometholone 0.1%, loteprednol 0.2%) on alternate days for many months; topical ciclosporin 0.05% may be useful as a steroid-sparing agent.
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Necrotizing stromal keratitis
Diagnosis: (a) stromal necrosis and melting; may be associated with an epithelial defect ( Fig. 6.10 ), (b) progression to scarring, vascularization, and lipid deposition ( Fig. 6.11 ).
Fig 6.10
Fig 6.11
Treatment: similar to aggressive disciform keratitis (see above), but oral antivirals are required; restoration of epithelial integrity is vital.
Neurotrophic ulceration
Pathogenesis: failure of epithelial integrity resulting principally from corneal anaesthesia.
Diagnosis: (a) nonhealing epithelial defect; (b) underlying stroma is grey and opaque, and may become progressively thin ( Fig. 6.12 ).
Fig 6.12
Treatment: as for any persistent epithelial defect; topical steroid to control any inflammatory component should be kept to a minimum.
Other considerations
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Prophylaxis: long-term daily oral aciclovir reduces the rate of recurrence of epithelial and stromal keratitis by approximately 50%. It should be considered in patients with frequent recurrences, particularly if bilateral or involving an only eye.
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Major complications: (a) secondary microbial infection, (b) glaucoma secondary to inflammation or prolonged topical steroids, (c) cataract secondary to inflammation or prolonged topical steroids, and (d) patchy iris atrophy following keratouveitis.
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Keratoplasty: carries a high risk of recurrence of active infection and rejection; prophylactic oral antivirals may improve the prognosis.
Herpes zoster ophthalmicus
Pathogenesis: VZV causes both chickenpox (varicella) and shingles (herpes zoster). After an episode of chickenpox, the virus travels to sensory ganglia and remains dormant, with reactivation thought to occur after specific immunity has faded. Herpes zoster ophthalmicus (HZO) is shingles involving a dermatome of the ophthalmic division of the trigeminal nerve. HZO occurs most frequently in the elderly, and immunocompromised patients tend to have more severe disease. Hutchinson’s sign refers to the rash of HZO affecting the skin on the tip and side of the nose ( Fig. 6.13 ), and correlates strongly with involvement of the eye.
Fig 6.13
Diagnosis and treatment of cutaneous lesions (see Chapter 1 ).
Ocular manifestations
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Acute epithelial keratitis: small fine dendritiform lesions ( Fig. 6.14 ); resolve spontaneously within a few days.
Fig 6.14
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Conjunctivitis: follicular and/or papillary is common; treatment is not required.
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Episcleritis: NSAIDs may be used if necessary.
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Scleritis and sclerokeratitis: treatment is with oral flurbiprofen.
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Nummular keratitis ( Fig. 6.15 ): may develop at the site of epithelial lesions; treatment is with topical steroids if symptomatic, with slow tapering.
Fig 6.15
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Stromal keratitis: responds to topical steroids but can become chronic and requires slow tapering.
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Disciform keratitis: less common than with herpes simplex infection; treatment is with topical steroids.
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Anterior uveitis: affects at least one-third of patients and can be associated with sectoral iris atrophy ( Fig. 6.16 ).
Fig 6.16
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Intraocular pressure (IOP) elevation: inflammatory or steroid-induced; prostaglandin derivatives should be avoided.
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Neuro-ophthalmological complications: may require intravenous antivirals and systemic steroids.
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Neurotrophic keratitis: common but usually mild and settles over months.
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Mucous plaque keratitis: uncommon; treatment involves topical steroids and acetylcysteine.
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Eyelids: cicatricial ptosis, entropion, and trichiasis.
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Reactivation: keratitis, episcleritis, scleritis, or iritis may occur years after an acute episode.
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Post-herpetic neuralgia: pain that persists for more than 1 month after the rash has healed develops in up to 75% of patients older than 70 years of age.
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Interstitial keratitis
Pathogenesis
Interstitial keratitis (IK) is inflammation of the corneal stroma without primary involvement of the epithelium or endothelium; usually an immune-mediated process. Congenital syphilis is the classic cause but is now rare in developed countries. IK is less common in acquired than in congenital disease. Other causes include herpetic and other viral infections, tuberculosis, sarcoidosis, and Cogan syndrome (see below).
Syphilitic
Diagnosis
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Systemic features of congenital syphilis: (a) early features include rhinitis, failure to thrive, rash, mucosal ulcers, fissures around the lips (rhagades), pneumonia, and neurological and cardiovascular problems; (b) late features include deafness, ‘saddle’ nose ( Fig. 6.17 ), ‘sabre’ tibiae, ‘bulldog’ jaw, Hutchinson’s teeth ( Fig. 6.18 ), and Clutton joints (painless effusions).
Fig 6.17
Fig 6.18
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Ocular features of congenital syphilis: (a) anterior uveitis, (b) IK, (c) subluxated lens, (d) ‘salt-and-pepper’ pigmentary retinopathy, and (e) Argyll Robertson pupils.
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Progression of IK in congenital syphilis: presents between the ages of 5 and 25 years with (a) deep stromal vascularization associated with clouding (‘salmon patch’); (b) the cornea clears over months and the vessels become nonperfused (‘ghost’ vessels; Fig. 6.19 ); (c) the healed stage is characterized by feathery deep stromal scarring ( Fig. 6.20 ).
Fig 6.19
Fig 6.20
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Ocular features of acquired syphilis: (a) anterior uveitis, (b) IK, (c) madarosis, (d) optic neuritis, (e) ocular motor nerve palsies, and (f) Argyll Robertson pupils.
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Treatment
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Acquired syphilis: penicillin, or alternatives if penicillin-allergic.
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Congenital syphilis: all patients with positive treponemal serology should be referred to a genitourinary medicine specialist for evaluation.
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Treatment of active syphilitic IK: systemic antibiotics, topical steroids and cycloplegics.
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Cogan syndrome
Pathogenesis: rare autoimmune systemic vasculitis, typically affecting young adults; characterized by intraocular inflammation and vestibuloauditory dysfunction.
Diagnosis
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Presentation: hearing loss and vertigo that may be separated by months.
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Signs: faint bilateral peripheral anterior stromal corneal opacities progressing to deeper opacification and neovascularization ( Fig. 6.21 ).
Fig 6.21
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Associated features: uveitis, scleritis and retinal vasculitis.
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Treatment
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Topical steroids: for keratitis.
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Systemic steroids: for scleritis, retinal vasculitis and vestibuloauditory symptoms.
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Immunosuppressive therapy: may be required.
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Protozoan keratitis
Acanthamoeba
Pathogenesis: Acanthamoeba spp. are commonly found in soil, water, and the upper respiratory tract. The cystic form is highly resilient. In developed countries, keratitis is most frequently associated with contact lens wear, especially if tap water is used for rinsing.
Diagnosis
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Presentation: blurred vision and pain, which may be severe and disproportionate to the clinical signs.
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Keratitis: (a) irregular and greyish epithelium ( Fig. 6.22 ), (b) pseudodendrites, (c) perineural infiltrates (radial keratoneuritis; Fig. 6.23 ) are pathognomonic, (d) diffuse or focal anterior stromal infiltrates may coalesce to a ring abscess ( Fig. 6.24 ) which may progress to melting ( Fig. 6.25 ), and to (e) slowly progressive stromal opacification and vascularization.
Fig 6.22
Fig 6.23
Fig 6.24
Fig 6.25
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Limbitis: progressing to scleritis.
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Differential diagnosis: herpes simplex keratitis.
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Investigations: (a) staining of corneal scrapings using periodic acid–Schiff or calcofluor white stains (Gram and Giemsa may also demonstrate cysts); (b) culture on non-nutrient agar seeded with dead Escherichia coli ; 30% culture negative; (c) immunohistochemistry; (d) PCR; (e) in vivo confocal microscopy; and (f) corneal biopsy.
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Treatment
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Debridement of infected epithelium.
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Topical amoebicides: (e.g. polyhexamethylene biguanide, chlorhexidine digluconate), hourly at first and gradually reduced; relapses are common and treatment may be required for many months.
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Topical steroids: avoided if possible.
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Pain control: oral NSAIDs (e.g. flurbiprofen).
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Keratoplasty: for residual scarring.
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Onchocerciasis
Pathogenesis: onchocerciasis (‘river blindness’) is caused by infestation with the parasitic helminth Onchocerca volvulus. It is the second most common infectious cause of blindness in the world and is endemic in areas of Africa.
Diagnosis
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Systemic features: (see Chapter 11 ).
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Signs: (a) anterior uveitis and pear-shaped pupillary dilatation, (b) sclerosing keratitis which starts at 3 and 9 o’clock and progresses ( Fig. 6.26 ) to involve the entire cornea, and (c) chorioretinitis (see Fig. 11.28 ); live microfilariae may be seen in the anterior chamber.
Fig 6.26
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Treatment: systemic ivermectin and topical steroids.
Bacterial hypersensitivity-mediated corneal disease
Marginal keratitis
Pathogenesis: hypersensitivity reaction to staphylococcal exotoxins and cell wall proteins.
Diagnosis
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Presentation: mild discomfort, redness, and lacrimation.
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Signs: (a) marginal subepithelial infiltrates separated from the limbus by a clear zone ( Fig. 6.27 ); (b) epithelial defects, characteristically smaller than the underlying infiltrate; (c) superficial scarring, slight thinning, and mild pannus; associated chronic anterior blepharitis is common.
Fig 6.27
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Treatment
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Spontaneous resolution generally occurs in 3–4 weeks, unless secondary infection occurs.
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Treat associated chronic blepharitis if necessary.
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Weak topical steroid three times daily for 1 week, sometimes in combination with an antibiotic.
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Oral tetracycline (erythromycin in children) may rarely be required.
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Phlyctenulosis
Pathogenesis: delayed hypersensitivity reaction to staphylococcal antigen.
Diagnosis
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Presentation: in a child or young adult with photophobia, lacrimation, and blepharospasm.
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Signs: (a) small white nodule on the conjunctiva ( Fig. 6.28 ) or limbus, associated with intense local hyperaemia; (b) a limbal phlycten which may extend onto the cornea ( Fig. 6.29 ) and leave a scar; (c) spontaneous resolution within 2–3 weeks; and (d) rarely thinning and perforation.
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