PERIPHERAL CORNEAL ULCERATION Characterized by crescent shaped destructiveinflammation of the juxtalimbal corneal stroma which isassociated with an epithelial defect, presence of stromalinflammatory cells, and progressive stromal degradationand thinning. Conjunctival, episcleral and scleral inflammation areusually present. It leads to progressive necrosis of the corneal stroma,leading to perforation and blindness. Collagen vascular diseases are responsible forapproximately half of the non-infectious cases of PUK. Rheumatoid arthritis (RA) is the most common collagenvascular disorder that causes PUK.
PATHOGENESIS Unlike the avascular central cornea, the peripheral cornea iscloser to limbal conjunctiva and derives its blood supply andlymphatics from the limbal capillary vessels, which extendapproximately 0.5 mm into the clear cornea. This is a source of immunocompetent cells, such asmacrophages, Langerhan’s cells, lymphocytes, and plasmacells. Immune complexes circulating in the blood of the patientswith collagen vascular disease can lodge at the ends of thelimbal vessels by virtue of their size and the restrictivemolecular sieving characteristics of the cornea.
PATHOGENESIS The peripheral cornea contains five times higher levels ofthe first component of the complement (C1) than does thecentral cornea which stimulates chemotaxis of theneutrophils to the area. The concentration of Ig M which is a large moleculedirected against Ig G (rheumatoid factor) is also greater atthis site. Immune complexes of rheumatoid factor and Ig M candeposit in the peripheral cornea and produceinflammation and corneal ulceration. Langerhans’ cells, which are the pre-eminent antigen-presenting cell, are also concentrated more densely in theperipheral cornea
Inflammatory stimulus in PC (bacteria, virus, fungi, and parasites)ORImmune complex deposition (in systemic immune diseases),. Malignancy, or Dermatologic conditionsMay produce local and systemic immune responses,Neutrophil recruitment and complement activation at limbus.Activated complement components increase vascular permeability andfurther generate chemotactic factors for neutrophils (eg. C3a,C5a), Infiltrate the peripheral cornea and release proteolytic and. collagenolytic enzymes, reactive oxygen metabolites, &. proinflammatory substances (such as PAF, leukotrienes, PG’s), .causing dissolution and degradation of the corneal stroma. The inflamed limbal conjunctiva itself is capable of producing. collagenase, which also causes stromal degradation.
Etiology of PUK: SYSTEMICInfectious Non infectious
PUK GRADING Peripheral Corneal ulceration should be graded as follows: < 25 percent depth of ulceration = 1, 25-50 percent = 2, 50-75 percent = 3, 75-100 percent = 4
INVESTIGATIONS 1. Complete blood cell count 2. Erythrocyte sedimentation rate 3. Serum creatinine, blood urea nitrogen 4. Rheumatoid factor (RF) in cases of RA (80% positive in RA) 5. Angiotensin-converting enzyme (ACE) which may be elevated insarcoidosis 6. Antinuclear antibodies (ANA) which are positive in patients with SLEand RA 7. Antineutrophil cytoplasmic antibodies (ANCA); C-ANCA sensitivity of96 percent for active generalized WG. 8. Anti-type II antibodies (positive in Relapsing polychondritis) 9. Complement - C3 and C4, CH50; in patients with SLE 10. Hepatitis B surface antigen (HBsAg); present in 40 percent ofpatients with PAN. 11. Chest X-ray and sinus CT scan to rule out WG, sarcoidosis, andtuberculosis
PERIPHERAL CORNEAL ULCERATION Mooren ulcer Rare, idiopathic disease characterized by progressivecircumferential peripheral, stromal ulceration with later centralspread. There are two types: the first affects predominantly olderpatients, often in only one eye, and usually responds well tomedical therapy; the second may be b/l, more aggressive,painful, and less responsive to treatment. Autoimmune mechanism is thought to be responsible forMooren ulcer. Corneal insult such as surgery, trauma or infection which ispresumed to act as a trigger in susceptible individuals. Rule out associated systemic autoimmune disease beforeconcluding the diagnosis to be Mooren ulcer
A) Local peripheral ulceration; (B) circumferential and central spread; (C) advanceddisease; (D) healed stage
Symptoms : Moderate-severe pain, photophobia andblurred vision (mainly due to astigmatism). Signs: Peripheral ulceration involving the superficial one-third ofthe stroma associated with variable epithelial loss. Progressive circumferential and central stromal thinningwith an undermined and infiltrated leading edge. Vascularization involving the bed of the ulcer up to itsleading edge but not beyond. The healing stage: thinning, vascularization and scarring.
Fluroscein Angiography: Initially shows capillary closureat the limbus and then leakage from vascularizationextending into the base of the ulcer. Complications: Severe astigmatism, Perforation following minor trauma (spontaneousperforation is rare), Secondary bacterial infection, Cataract Glaucoma
TREATMENT Topical steroids as frequently as hourly are combined with alow-frequency prophylactic topical antibiotic. Ciclosporin (up to 2%) may be effective, but may takeweeks to exert a significant effect. Adjunctive topical therapy includes artificial tears andcollagenase inhibitors such as acetylcysteine 10%. Conjunctival resection: combined with excision of necrotictissue, is performed if there is no response to topical steroids. The excised area should extend 4 mm back from the limbusand 2 mm beyond the margins of the lesion. Resection maybe combined with keratoepithelioplasty to produce a physicalbarrier against conjunctival regrowth and further melting.Steroids are continued postoperatively.
TREATMENT CONTD.. Systemic immunosuppression: earlier for bilateraldisease, or if involvement is advanced at first examination. Options include ciclosporin (5 mg/kg), prednisolone,methotrexate and azathioprine. Systemic collagenase inhibitors: doxycycline may bebeneficial. Lamellar keratectomy: involving dissection of theresidual central island in advanced disease may removethe stimulus for further inflammation. Visual rehabilitation: involving deep anterior lamellar orpenetrating keratoplasty may be considered onceinflammation has settled. Surgery is covered with systemic immunosuppression toreduce the risk of recurrence
TERRIEN MARGINAL DEGENERATION Terrien disease is an uncommon idiopathic thinning of theperipheral cornea. About 75% of affected patients are male and the condition isusually bilateral although involvement may be symmetrical. Presentation: usually after the 4th decade with initiallyasymptomatic peripheral corneal lesions.
Signs: Fine, yellow-white, punctate stromal opacities frequentlyassociated with mild superficial vascularization, usuallystart superiorly, spread circumferentially and areseparated from the limbus by a clear zone. On cursoryexamination they may resemble arcus senilis. Slowly progressive circumferential thinning results in aperipheral gutter, the outer slope of which shelvesgradually, while the central part rises sharply. Perforation may rarely occur either spontaneously orfollowing blunt trauma. Gradual visual deterioration occurs as a result ofincreasing corneal astigmatism. Pseudopterygia may develop in long-standing cases atpositions other than the 9 o’clock and 3 o’clock meridian
TREATMENT Safety spectacle lenses (polycarbonate as a minimum) ifthinning is significant. Contact lenses for astigmatism. Scleral lenses, or evensoft lenses with rigid gas permeable ‘piggybacking’, arelikely to be necessary. Surgery, involving either crescent-shaped excision of thegutter with suturing of the margins or peripheral lamellartransplantation, gives variable results. Tectonic’ corneal grafting for perforation or threatenedperforation. Topical lubricants or weak topical steroids forinflammatory episodes, the latter with caution because ofthe risk of promoting thinning.
PELLUCID MARGINAL DEGENERATION Pellucid marginal degeneration(PMD; keratotorus), is adegenerative corneal condition,often confused with keratoconus. It is typically characterized by aclear, bilateral thinning (ectasia) inthe inferior and peripheral region ofthe cornea, although some casesaffect only one eye. The cause of the disease remainsunclear (idiopathic). The word "pellucid" means clear,indicating that the corneas retainclarity in pellucid marginaldegeneration.
SYMPTOMS & SIGNS Pellucid marginal degeneration is usually asymptomatic,except for the progressive deterioration in uncorrectedand spectacle corrected visual acuity caused by theirregular astigmatism induced by the corneal ectasia. Episodes of corneal hydrops with resultant pain, as seenin keratoconus, have been reported, but they occur onlyrarely.
TREATMENT OF PMD Medical Mx Spectacles: To prevent trauma, perforation Softlenses Large dia RGP lenses Hybrid lenses Bitoric RGP lenses Scleral lenses
TREATMENT OF PMD Surgical Mx Penetrating keratoplasty Diathermy Lamellar keratoplasty C-shaped lamellar keratoplasty Thermokeratoplasty Lamellar crescentic resection of the affected area and re-apposition of normalthickness cornea from each side of the affected area Wedge resection Full-thickness crescentic resection Replacement by a freehand corneoscleral graft Tectonic lamellar grafting followed by a central penetrating keratoplasty Large epikeratophakia graft Intrasomal ring segment implantation using a femtosecond laser to makelamellar dissections Intracorneal ring segments and bitoric or intralimbal rigid gas-permeable lensesmay also improve vision.
PUK ASSOCIATED WITH SYSTEMIC AUTOIMMUNEDS Peripheral ulcerative keratitis (PUK) may precede or followthe onset of systemic disease. Severe peripheral corneal infiltration, ulceration or thinningunexplained by evident ocular disease should prompt asearch for an associated systemic collagen vasculardisorder . Clinical features: Crescentic ulceration and stromal infiltration at the limbus. Limbitis, episcleritis or scleritis are usually present. Circumferentially and occasionally central spread; incontrast to Mooren ulcer the process may also extend intothe sclera. End-stage disease may result in a ‘contact lens’ cornea
ASSOCIATED SYSTEMIC DISEASE 1. Rheumatoid arthritis is the commonest systemic association. PUK involves both eyes in 30% of cases and tends to affect patientsduring the late and advanced vasculitic phase. Patients with rheumatoid arthritis may also develop the following non-ulcerative types of keratitis:A. Peripheral stromal thinning : characterized by gradual resorption ofperipheral stroma leaving the epithelium intact. Perforation may occur inadvanced cases.B. Sclerosing keratitis: characterized by gradual thickening andopacification of the corneal stroma adjacent to a site of scleritis.C. Acute central corneal melting may occur in association withinflammation or severe dry eye.
2. Wegener granulomatosis is the second mostcommon systemic association of PUK. In contrast with rheumatoid arthritis ocular complicationsare the initial presentation in 50% of cases. 3. Relapsing polychondritis is more commonlyassociated with episcleritis or scleritis than with PUK. 4. Systemic lupus erythematosus is a rare association.
Keratitis in systemic collagen vascular disease. (A) Early peripheralulcerative keratitis; (B) ‘contact-lens’ cornea; (C) peripheral melting withperforation and iris prolapse; (D) sclerosing keratitis
TREATMENT Consider medicine opinion. Systemic high dose steroids are used to control acutedisease and cytotoxic therapy is required for longer-termmanagement to obviate the side effects of steroids.Cyclophosphamide is especially useful for Wegenergranulomatosis. Topical lubricants (preservative-free). Topical antibiotics may be considered as prophylaxisagainst infection if an epithelial defect is present. Oral tetracycline such as doxycycline 100 mg b.d. mayretard thinning due to an anticollagenase effect.
Topical steroids are generally avoided as they mayworsen thinning, although relapsing polychondritis maybe an exception when frequent steroid instillation seemsto be helpful. Conjunctival excision may be considered if medicaltreatment is ineffective. Corneal gluing or amniotic membrane patching forperforation. Keratoplasty (preferably lamellar) may be required forperipheral corneal perforation.
UPDATE ON PUK’S Recently, infliximab, a chimeric antibody againstproinflammatory cytokine tumor necrosis factor-alpha, wasreported to be effective in cases refractory to conventionalimmunomodulatory therapy in PUK. The potential side effects of these therapies require closefollow-up and regular laboratory surveillance. (Update on peripheral ulcerative keratitis, DovepressJournal: Clinical Ophthalmolgy, Authors: Yagci APublished Date May 2012)