Peripheral  Ulcerative Keratitis

Agarwal A. MD, Panda A. MD, FAMS, FICS, FICO, MRC Ophthalmology

Cornea and Ocular Surface Disease Services, Dr. Rajendra Prasad Centre for Ophthalmic Sciences,  

New Delhi

ABSTRACT:

Peripheral Ulcerative Keratitis is a relatively infrequent disease, but it acquires relevance from the fact that it may be ocular manifestation of the life threatening systemic collagen vascular disease and occasionally it may be the only sign,  which may demand thorough systemic evaluation. The etiology of the condition is essentially an autoimmune condition which preferentially involves the periphery of the  cornea, because of  the disproportionately higher distribution of immunological factors in the periphery. Though peripheral it may progressively involve the entire cornea in due course of time. Besides the vision threatening complications of corneal perforation  and corneal opacification , it may be often associated with other serious ocular manifestations  like  episcleritis, necrotizing and non-necrotizing sclerirtis, keratoconjunctivitis sicca,   choroidal lesions, retinal vasculitis, optic neuritis, papillitis, orbital pseudotumor and extraocular muscle dysfunction besides induced astigmatism. The diagnosis is predominantly clinical, but the systemic immunological work up (including laboratory work up) may lead  to a pinpoint diagnosis. The various treatment modalities available include medical downregulation of autoimmune response by corticosteroids, systemic immunosuppressants or their combination. Topical steroid therapy may be fruitful in achieving a fast response but requires caution, as it may lead to progressive thinning of cornea and perforation. Various surgical procedures like conjunctival resection, keratoepithelioplasty and tissue adhesives are also directed  to  prevent migration  ofl  immunological  factors.

Peripheral ulcerative keratitis (PUK) is a form of ocular inflammation that involves the peripheral portion of cornea and may be associated with systemic conditions such as Rheumatoid Arthritis(RA), Wegener’s Granulomatosis(WG), and other systemic conditions. It is a potentially devastating disorder consisting of a crescent-shaped destructive inflammation at the margin of corneal stroma that is associated with an epithelial defect, presence of stromal inflammatory cells, and progressive stromal degradation and thinning.

The onset of Peripheral Ulcerative Keratitis has been linked to various anatomical factors of central and peripheral cornea and adjoining limbus. Though the local concentration of small and medium weight proteins like IgA, IgG and most complements are similar in central and peripheral cornea, the peripheral cornea has been found to be associated with higher concentrations of higher molecular weight(HMW) protein molecules like IgM and complement C1(5 times), possibily owing to tight arrangement of corneal lamellae. The Peripheral cornea is also known to harbour reservoir of various inflammatory cells like neutrophils, lymphocytes, plasma cells and mast cells and antigen presenting  Langerhans dendritic cells, which is present only in conjunctiva and peripheral cornea. Besides, the peripheral cornea is also supplied by capillary arcades (supply peripheral 0.5 mm cornea).
The major pathophysiologic mechanism  is a result of degradation and tissue  necrosis of corneal stroma produced by degradative enzymes, which are released primarily by neutrophils attracted into the area by diverse stimuli.

The etiology of PUK may broadly be divided on the location and extent of causative factor as ocular (localized) and systemic(Table 1). Further the above two can further be classified on the nature of inciting insult as infectious and non-infectious.
Approximately half of the etiology of PUK is catered by autoimmune vasculitic disease (endothelial injury), attributed to deposition of immune complexes on vascular endothelium or leucocyte mediated cytotoxicity caused by antineutrophil cytoplasmic antibodies (ANCA) directed against neutrophil granule enzymes mainly antiprotease-3 and antimyeloperoxidase (ANCA positive pauci-immune vasculitis). Autoimmune  vasculitis may manifest variably as PUK, necrotizing scleritis, Keratitis, retinal vasculitis and optic neuropathy.
Whatever may be the etiology, the final common pathway consists of release of proteolytic and collagenolytic enzymes from inflammatory cells. Early diagnosis and treatment of  peripheral Keratitis may be important in altering the prognosis of the ocular and also a possibly life threatening systemic disease.

Table 1: Etiology of PUK

Diagnostic tests and Systemic Review:
After a systemic review, a preliminary diagnosis of a few systemic syndromes appears.  The specific diagnosis is achieved by combining the clinical diagnosis with a few confirmatory laboratory tests. Blanket investigations for PUK testing is not required.
Within the ANA (HEp-2 cell substrate) the detection of anticentromere antibodies (centromere-specific pattern) provides an important tool in the diagnosis of PSS, especially the limited cutaneous form (CREST syndrome: calcinosis, Raynaud’s phenomenon, esophageal hypomotility, sclerodactyly, telangiectasia).

Ocular tissue biopsy in suspected autoimmune PUK such as Mooren’s ulcer and systemic vasculitic syndrome-associated PUK can be very helpful in reaching a specific diagnosis and deciding a specific therapy.
Systemic review may provide important clues to the specific systemic diagnosis. The detection of saddle nose deformity and/ or auricular pinnae deformity, secondary to inflammation of the involved cartilage can be important clues to the diagnosis of Relapsing Polychondritis(RP). Saddle nose deformity and/ or nasal ulcers can be a sign in Wegener’s Granulomatosis(WG). A butterfly rash across the nasal bridge extending to the malar areas and/or alopecia suggest the diagnosis of Systemic Lupus Erythematosus (SLE).  Loss of facial expression and normal skin wrinkles associated with facial  telengiectasias suggest the diagnosis of Progressive Systemic Sclerosis(PSS). Erythema, telengiectasias, papules and pustules in forehead, cheeks, chin and nose with and without rhinophyma can establish the diagnosis of Acne Rosacea. However this is not frequent in India. One case report documents peripheral corneal ulceration as the presenting sign of temporal arteritis.Tenderness and erythema of temporal artery suggest the diagnosis of Giant Cell arteritis(GCA).

Table 2.Clinical findings in Peripheral Ulcerative Keratltis and suspected systemic disease

Ocular Investigations: include

• Scraping and culture of the lesion  to rule out underlying infection.
• Conjunctival resection/biopsy may be helpful in removing the limbal source of collagenases and other factors causing progressive ulceration rather than any diagnostic finding.

Table 3 .Laboratory Tests for Suspected Systemic Diseases

ESR, erythrocyte sedimentation rate; ANA, antinuclear antibodies; anti-dsDNA, antibody to double-stranded DNA; anti-sm, anti-RNP, anti-Ro, anti-La, antibodies to small nuclear ribonucleoproteins-Sin, -RNP, -Ro, and -La: CIC, circulating immune complexes; IgG, IgA. IgM, IgE, immunoglobulins: C, complement (C3, C4, CH50): Cryog, cryoglobulins; RF, rheumatoid factor: HBSAg. hepatitis B surface antigen: WBC, white blood count; ANCA, antineutrophil cytoplasmic antibodies.

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