Diseases of Cornea

Applied Anatomy:

• anterior 1/6th eyeball’s fibrous coat.
• 5layers:
  1. Str-sq-E
  2. Bowmann’s layer [condensed collagen]
  3. Stroma [0.5mm] – has collagen lamellae [arraged parallel to adj lamellae & perpendicular to alt layers], proteoglycans, macrophages
  4. Descemet’s membrane -strong & very resistant to chemicals/ trauma/ pathological changes, can regenerate, peripherally ends as Schwalbe’s line at anterior limit of trabecular meshwork.
  5. Endothelium – hexagonal cells giving mosaic appearance, lost with age [but only after 75% loss, affects active pump function]
• thickness = 0.52 [centre] – 0.7[periphery]
• anterior elliptical surface’ s horizontal diameter in adult / by 2yrs = 11.7mm; at birth = 10mm.
• central area of 5sqmm is powerful refraction surface = 45D [3/4th total 60D of eye]
• refracting medium is due to transparency maintaimed by stromal lamellar arrangement, avscularity & dehydration from barrier effect [endo & epithelium] & active [HCO3-]pump. This requires metabolic energy [in epithelium is 10times that in endothelium] from glucose [through aqH & perilimbal bv] & oxygen [active epithelial uptake from air]
• avascular with only anterior ciliary.N innervation; subconjunctiva overlapping peripheral cornea has anterior ciliary bv loops invading about 1mm

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Congenital anomalies:

CLOUDY:

D/D: [STUMPED] sclerosis, tears in descemet, ulcer, metabolic, posterior corneal defect, endothelial dystrophy, dermoid.

Megalocornea: [often associated with Marfan's]

diameter at birth = adult 11.7 or at 2yr >13mm.

D/D: buphophthalmos [IOP raised & cloudy due to Haab's striae in descemet], Keratoglobus [normal diameter but protruded]

Microcornea:

<10mm

Cornea plana:

flat & results in high astigmatism [<45D]

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Corneal inflammations: KERATITIS

• edema
• infiltrate
• congestion

Classification:

Morphological:

Ulcerative:

1. central; peripheral
2. purulent [bacterial,fungal]; non-pur [chlamydial, viral, allergic]
3. simple; hypopyon
4. superficial, deep, perforated
5. non; sloughing

Non-ulcerative:

1. superficial – diffuse; punctate
2. deep – nonsup [interstitial, discifrom, sclerosing, keratitis profunda]; suppurative [meatstatic abscess- central; posterior]

Etiological:

1. Infective – bacterial, viral, fungal, chlamydial, protozoal, spirochaetal
2. Allergic – phlyctenular, vernal, atopic
3. Trophic – exposure, neuroparalytic
4. skin disease associated
5. collagen vascular disorder associated
6. Traumatic – mechanical, chemical, thermal
7. idiopathic – Mooren’s, superior limbic keratoconj, Thygeson superficial puctate keratitis

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Bacterial corneal ulcer:

Etiology:

1. Epithelial damage: abrasion [foreign body, cilia, concretion, trauma], dryness [xerosis, exposure], trophic [neuroparalytic], necrosis [keratomalacia], desquamation [edema]
2. Infection: [rare endogenous since avascular], exogenous sources like conj, sclera, uvea, lacrimal sac, foreign body, water, air.
3. Organisms: staph, strep, pseud, Ecoli, Pr, Kl, virulent ones like Neisseria & Coryne even thr intact epithelium.

Pathology:

Localised ulcer:

1. Progressive infiltration – into epithelium from circulation.
2. Ulceration -
   1. grey swelled [infiltration & exudation] walls & floor of ulcer.
   2. necrosis & sloughing of epi, Bowman’s, stroma.
   3. circumcorneal hyperaemia – leading to purulent exudates on cornea.
   4. toxic congestion of iris & ciliary body – leading to exudation into anterior chamber [hypopyon]

   extension leading to diffuse superficial ulceration or deeper penetration to desmetocele / perforation.

3. Regression – induced by treatment / immunity, line of demarcation around ulcer with WBC phagocytosing organisms & necrotic debris, results in initial enlargement of ulcer & superficial vascularization that boosts immune response causing healing.
4. Cicatrization – progressive permanent epithelialization & underneath fibrosis thickens stroma & pushes up epithelium. Scarring does’nt occur if only epithelium is involved, but with other layers, opacities form [NEBULA -Bowmann,few lamellae; MACULA -1/3rd stroma; LEUCOMA ->1/2 stroma]

Perforated ulcer:

• deeper upto descemet which is tough so bulges as desmetocele
• perforates on exertion resulting in aqH escape & fall in IOP & iris [lens diaphragm] falls forward & plugs the perforation [if small & opposite] & healed by cicatrization = ADHERANT LEUCOMA

Sloughing ulcer:

• with virulent organism or low immunity.
• complete cornea except for the rim sloughs & total iris prolapse occurs
• iris inflames & exudates cover iris & block pupil, this organizes to thin fibrous layer over which corneal/conj epithelium grows & forms PSEUDOCORNEA.
• this thin false cornea with the plastered iris behind, due to IOP bulges forward = ECTATIC CICATRIX = ANTERIOR STAPHYLOMA which is lobulated due to scar bands & blackened with iris tissue.

Symptoms & signs:

depend on virulence of organism & host immunity.

1. Pain – due to swollen lids, blepharospasm & toxic effect on nerves.
2. reflex hyperlacrimation
3. Photophobia -ambient light intolerance to nerves.
4. redness due to ciliary congestion, conjunctival hyperaemia & chemosis.
5. Blurred vision – due to corneal haze [rough yellow white ulcerative areas]
   1. staph – oval & opaque
   2. Pseudomonas – irregular with green pus & ground glass surrounding
   3. enterobacteriae – shallow with grey pus & diffuse opacity & ring corneal infiltrates may be present due to endotoxins.
6. muddy iris & small pupil due to toxin induced waterlogged iritis
7. hypopyon corneal ulcer shows marked clinical features. It is more common in old debilitated & alcoholic & esp with pneumococci & Pseudomonas pyocyanea, other pyogens. Mechanism – when toxin induced iritis[sterile] is severe, there is outpouring of infiltrate from bv & gravitate into anterior chamber. When ulcer heals, it gets absorbed
   • Ulcus serpens is characteristic hypopyon caused by Pneumococcus. It is a grey/yellow disc near corneal centre, with one edge cicatrized & other edge shows infiltration along which serpiginous spread over cornea occurs.

Complications:

1. Toxic iridocyclitis – due to absorption of toxins in anterior chamber from purulent corneal ulcer.
2. Secondary glaucoma – from fibrinous exudates blocking the angle.
3. Descemetocele – usually due to virulent organism; associated with severe pain & is an impending perforation.
4. Perforation of corneal ulcer – sudden strain like cough,sneeze, orbicularis ms spasm bursts impending perforation & relieves pain with oozing aqueous. Sequelae:
   • Iris prolapse – to plug the perforation.
   • Subluxation / anterior dislocation of lens – due to sudden stretching & rupture of zonules.
   • Anterior capsular cataract – due to lens coming in contact with the lens through pupil.
   • Corneal fistula – when iris plug is not formed, aqueous leaks through fistula continously.
   • Secondary infection leading to uveitis, endophthalmitis, panophthalmitis.
   • Vitreous or choroidal haemorrage due to sudden lowering of IOP.
   • Corneal scarring from healed ulcer causes permanent visual impairment [nebula, macula, leucoma, ectatic cicatrix / kerectasia, adherent leucoma / anterior staphyloma.

Management:

Ocular examination:

gross lesions in diffuse light.

regurgitation & syringing of lacrimal sac.

biomicroscopic examination of ulcer with fluorescein dye.

scraping the ulcer base & margins with kimura spatula / 20G hypodermic needle for Gram, Giemsa, KOH, Calcofluor white, blood agar, SDagar.

Rx:

Uncomplicated corneal ulcer: urgent eradication of infection since vision threatening.

Specific treatment:

1. Local broad spectrum antibiotics -
   • topical drops of fortified gentamycin+cephazoline every 1hr for first few days then diluted drops & every 2hr.
   • ointment at night.
   • for sloughing ulcer - subconjunctival injection of gentamycin+cephazoline daily for 5days.
2. Systemic antibiotics for fulminating perforation.

Non-specific treatment:

1. Cycloplegics - to prevent ciliary spasm pain, posterior synechia & relieve anterior ciliary.A [increase antibodies & reduce exudation]
2. Systemic NSAIDs
3. Vit A,B,C for hastening healing.

General measures:

1. Hot fomentation
2. Goggles from strong light
3. Bandage if no acute conjunctivitis & copius discharge.

Non-healing corneal ulcer:

removal of know causes:

1. Local causes – raised IOP, concretions, misdirected cilia, foreign body, dacryocystitis, lagophthalmos, vascularization, inadequate therapy, wrong diagnosis.
2. Systemic causes – DM, anaemia, malnutrition, chronic diseases, systemic steroids.

Debridement: scraping necrosed debis from ulcer floor to hasten healing

Cauterisation

Peritomy : for excessive vascularization

Impending perforation: prevent perforation & its complications.

Strict bed rest – avoid sneezing, coughing, straining during stool.

Pressure bandage for external support.

Lowering IOP with acetazolamide, mannitol, glycerol, timolol, paracentesis.

Tissue adhesive glue like cynoacrylate.

Conjunctival flap, bandage soft contact lens for corneal support.

keratoplasty [tectonic graft]

Perforated corneal ulcer:

Tissue adhesive glue like cynoacrylate.

Conjunctival flap, bandage soft contact lens for corneal support.

best is an urgent keratoplasty [tectonic graft]

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MYCOTIC CORNEAL ULCER

Etiology:

Common causative fungi: Aspergillus, Cnadida, Fusarium

Infection mode: injury from vegetative matter or animal tail, systemic / local (eye diseases) immunosuppression.

Catalysts: antibiotics (disturb symbiosis between bacteria & fungi), steroids (fungi shift from symbiosis to facultative saprophytes).

Clinical features:

Symptoms are similar to central corneal ulcer but are less marked & with indolent course : pain, redness, watering, photophobia, blurred vision.

Typical signs of ulcer: dry grey rolled out margins with stromal feather like extensions. Usually a big hypopyon is present which is non-sterile since fungi penetrate anterior chamber without penetration. Yellow immune ring & Satellite lesions may be present.

Lab Diagnosis: KOH, Calcoflour, Gram. Giemsa for fungal hyphae & Sabourauds agar culture.

Rx:

Anti-fungals

Non-specific: cycloplegics, NSAIDs, vit A B C, dry hot fomentation, dark goggles, bandage.

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VIRAL CORNEAL ULCERS

Viruses tend to affect epithelium of conjunctiva & cornea, hence VIRAL KERATOCONJUNCTIVITIS.

Herpes simplex : extremely common

Etiology:

1. HSV – DNA virus. Man is the only host. Epitheliotropic, but may become neurotropic
2. HSV1 causes infection above waist through close contact like kissing.
3. HSV2 causes infection below waist(genitals), ocular infection in neonates during parturition of infected mother.

Clinical features:

Primary herpes:

self-limiting disease of childhood but latent in trigeminal ganglion.

1. periorbital skin lesions : vesicular
2. acute follicular conjunctivitis
3. epithelial keratitis – punctate or diffuse

Recurrent herpes

Periodic reactivation of latent infection usually with UV rays, fever,chr diseases, exhaustion, trauma,mestrual stress, immunosupression.

Epithelial keratitis:

pain, lacrimation, photophobia.

• 1. punctate epithelial keratitis
  2. Debdritic ulcer – linear branching with knobbed ends; diminshed corneal sensations; flourescein stains floor & rose bengal stains viruses at margin.
  3. Geographical ulcer – amoeboid; hastened formation by steroid use in dendritic ulcer.
  4. Rx:
     1. Antivirals for 7days (idoxuridine, triflurothymidine, vidarabine, acyclovir)
     2. If resistance / allergy to antivirals / non-compliance : Mechanical debridement with cotton : involved & surrounding area.

  Stromal keratitis:

  1. Disciform :
     • focal disc like patch of edema due to delayed hypersensitivity ot virus; accompanying iritis, KPs, dimished corneal sensations.
     • mild pain, watering, marked vision loss.
     • Rx: diluted steroid drops 5times/day, Antivirals 2times/day [if with epithelial keratitis, use 5days before steroid use.
  2. Diffuse :
     • invasion + necrosis + blotchy white infiltrates under ulcer + [iritis + KPs + stromal vascularization
     • pain, redness, photophobia
     • Rx: similar to disciform but unsatisfactory; Keratoplasty in quiet eye.
  • due to mechanical healing problem of previous herpetic ulcer.
  • indolent linear / oval epithelial defect.
  • Rx: to promote healing - artificial tears, soft contact lens, lateral tarsorrhaphy.

Sterile trophic / Meta-herpetic

Iridocyclitis

Herpes zoster : Gasserian ganglion[5th.N] infection

Etiology:

• Varicella zoster – DNA virus. neurotropic.
• childhood infection leaves latent virus in sensory ganglion of trigeminal which gets reactivated in old age / decreased cell-mediated immunity to travel down ophthalmic N divs.

CFs:

• unilateral side of head with frontal.N div affected more than lacrimal or naso-ciliary.N
• 50% cases show ocular manifestations esp if (cutaneous involvement of naso-ciliary.N) side/tip of nose presents vesicles [HUTCHINSON'S rule]
• General symptoms: sudden fever, malaise, characteristic neuralgia.
• after 3days & for 3wks, periorbital skin lesions : red & edematous –> vesicles –> pustules –>ulcer crusts –> pitted scars.
• severe neuralgia & anaesthesia diminish after eruptive phase. If persistant called post-herpetic neuralgia & anaesthesia dolorosa.
• Ocular lesions after eruptive subsidence & as 2 or more of:
  1. Conjunctivitis [most common]- mucopurulent with petechiae, acute follicular with lymphadenopathy.
  2. Keratitis [40% , may precede neuralgia/eruptions]-
     1. puctate epi
     2. MICROdendritic ulcer [peripheral stellate]
     3. Nummular [33%] – multiple tiny granular deposits with stromal hazy halo
     4. Disciform [50%] – always preceded by nummular.
     5. Neuroparalytic ulcers – from Gasserian destruction.
     6. Exposure keratitis – due to facial palsy.
  3. Scleritis, episcleritis [50%]
  4. Iridocyclitis [+hypopyon/hyphaema]
  5. Phthisis bulbi – from necrosis / vasculitic ischaemia.
  6. Secondary Glaucoma – from trabeculitis / synechia.
• Neurological: motor.N [3,4,6,7] palsy, optic neuritis, encephalitis in severe cses.

Rx: vigorous to prevent scarring, post-herpitic neuralgia, devastating complications.

• NSAIDs for initial 2wks [pethidine if severe pain]
• systemic acyclovir 5daily/10days – started with rash appearrance.
• steroid+antibiotic skin ointment 3times/day
• systemic steroids – for neuro complications [post-herpetic neuralgia, palsy, neuritis]. CI- in old age.
• cemitidine – for pruritis
• amytriptyline
• Keratitis, Iridocyclitis, Scleritis – topical steroid, acyclovir, cycloplegics.
• Glaucoma – timolol, acetazolamide.
• Neuroparalytic ulcer – lateral tarsorrhaphy
• visual rehabilitation of scarring – keratoplasty

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Allergic keratitis

-phlyctenular, vernal, atopic.

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TROPHIC CORNEAL ULCER

due to epithelial metabolic disturbance.

Neuroparalytic keratitis:

Pathogenesis:

due to corneal sensory.N [5th] paralysis causing antidromic corneal reflex disturbances leading to epithelial metabolites accumulation –> edema, exfoliation, ulceration.

Congenital causes:

dysautotomia, pain insensitivity

Acquired causes:

Alcohol block / electrocoagulation / external tumor pressure / injury / leprosy, syphilis, Hsimplex, Hzoster destruction of Gasserian ganglion

sensory root section of trigeminal.N for neuralgia

CFs: [relapses are common]

loss of corneal sensations

marked ciliary congestion

interpalpebral punctate epithelial erosions & ulceration

Rx: [slow healing]

antibiotic + atropine ointment

lateral tarsorrhaphy for relapses + artificial tears

Exposure keratitis

Causes for lagophthalmus:

Extreme proptosis, facial palsy, severe ectropion, symblepharon, deep coma, during sleep

Pathogenesis:

interpalpebral dry epithelium –> dessication —>cast off —>invasion.

CFs:

punctate epithelial keratitis, necrosis, ulceration, vascularization. [bacterial superinfection - deep ulcer, perforation]

Rx:

artificial tears, soft contact lens for moderate exposure, bandage during sleep, treat cause of exposure or in untreatable cases tarsorrhaphy

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Idiopathic corneal ulcers

Mooren’s ulcer / Rodent / Chronic serpiginous

Etiology:

degenerative due to vasculitic ischaemea, conjunctival collagenase, autoantibodies.

CFs:

BENIGN – unilateral, indolent, in old age

VIRULENT – bilateral, rapidly progressive with scleral involvement, in young age

• symptoms – severe pain, photophobia, lacrimation, defective vision
• signs – initial grey patchy infiltrates on peripheral cornea which coalesce to form superficial ulcer over whole cornea with white overhanging edge & vascularized base.

Rx: unsatisfactory

topical steroids, conjunctival excision & recession, topical collagenase inhibitors, immunosupressants, soft contact lens for pain, graft.

Non-ulcerative : SUPERFICIAL PUCTATE KERATITIS

multiple spotty lesions [puctate erosions, punctate keratitis, filamentary keratitis] in epithelium, Bowmann’s & superficial lamellae.

some Causes:

• Viral – Hsimplex, Hzoster, adeno
• chlamydial
• staph toxin
• Trophic keratitis
• allergic[vernal] or irritative[idoxuridine]
• skin disorders like acnerosacea & pemphegoid
• Keratoconjunctivitis sicca
• Idiopathic – thygeson’s, theodore’s
• photoophthalmitis

CFs:

pain, photophobia, lacrimation, conjunctivitis

Rx: symtomatic

topical steroids, artificial tears, treat cause.

PHOTO-OPHTHALMIA

cause:

UV rays, short circuit, welding, snow

CFs:

latency 5hrs. multiple epithelial erosions. burn, lacrimation, photophobia, blepharospasm, palpebra conjunctival swelling, retrotarsal folds

Rx:

Crooker’s glass, cold compresses, antibiotic bandage.

Non-ulcerative Non-suppurative Deep keratitis : INTERSTITIAL KERATITIS

inflammation of stroma without primary involvement of epithelium or endothelium : causes – syphilis, TB, leprosy, sarcoidosis, malaria, trypanosomiasis, COGAN’s syndrome [interstitial keratitis, tinnitus, vertigo, deafness]

Syphilitic / leutic interstitial keratitis

hypersensitive inflammation to new little invasion after foetal treponema exposure

90% congenital (manifests after 5-15yrs)- bilateral ; acquiredc – unilateral.

Tuberculous interstitial keratitis

unilateral & sectorial usually lower cornea.

CFs:

• late manifestation or part of HUtchinson’s triad [I.keratitis, H.teeth, vestibular deafness]
• PROGRESSIVE stage [2wks]- deep stroma & endothelial edema, pain,lacrimation, photophobia, circumcorneal injection, diffuse corneal haze
• FLORID stage [2mos]- deep vascularization [salmon patch appearance due to corneal haze], Epulit at limbus from heaping of superficial vascularization & conjunctiva.
• REGRESSION stage [1-2yrs]- inflm resolves slowly from periphery due to vascular invasion, leaving behind some opacities & ghost vessels.

Rx:

1. LOCAL- topical steroids & cycloplegics
2. SYSTEMIC- penicillin for syphilis, anti-tubercular drugs for TB.

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CORNEAL DEGENERATIONS

Age related degenerations:

1. Arcus senilis
2. Vogt’s white limbal girdle
3. Hassal-Henle bodies

Pathological degenerations:

1. Lipoid keratopathy / Fatty degeneration
2. Band keratopathy / Calcific degeneration
3. Salzmann’s nodular degeneration
4. Furrow degeneration / senile marginal degeneration
5. Keratotorus / Pellucid marginal degeneration
6. Terrien’s marginal degeneration

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CORNEA DYSTROPHIES

Anterior dystrophies:

1. Epithelial basement membrane dystrophy
2. Reis-Buckler dystrophy
3. Meesman’s dystrophy / Juvenile epithelial dystrophy
4. Stocker-Holt dystrophy

Stromal dystrophies:

1. Granular dystrophy / Groenouw 1
2. Macular dystrophy / Groenouw 2
3. Lattice dystrophy
4. Schnyder’s crystalline dystrophy

Posterior dystrophies:

1. Cornea guttata
2. Fuchs epithelial-endothelial dystrophy
3. Posterior polymorphous dystrophy
4. Congenital heriditary endothelial dystrophy [CHED]

Ectatic dystrophies:

1. Keratoconus
2. keratoglobus