Vernal keratoconjunctivitis: a severe allergic eye disease with remodeling changes.

Vernal keratoconjunctivitis (VKC) is an unusually severe sight-threatening allergic eye disease, occurring mainly in children. Conventional therapy for allergic conjunctivitis is generally not adequate for VKC. Pediatricians and allergists are often not familiar with the severe clinical symptoms and signs of VKC. As untreated VKC can lead to permanent visual loss, pediatric allergists should be aware of the management and therapeutic options for this disease to allow patients to enter clinical remission with the least side effects and sequelae. Children with VKC present with severe ocular symptoms, that is, severe eye itching and irritation, constant tearing, red eye, eye discharge, and photophobia. On examination, giant papillae are frequently observed on the upper tarsal conjunctiva (cobblestoning appearance), with some developing gelatinous infiltrations around the limbus surrounding the cornea (Horner-Trantas dot). Conjunctival injections are mostly severe with thick mucus ropy discharge. Eosinophils are the predominant cells found in the tears and eye discharge. Common therapies include topical antihistamines and dual-acting agents, such as lodoxamide and olopatadine. These are infrequently sufficient and topical corticosteroids are often required for the treatment of flare ups. Ocular surface remodeling leads to severe suffering and complications, such as corneal ulcers/scars. Other complications include side effects from chronic topical steroids use, such as increased intraocular pressure, glaucoma, cataract and infections. Alternative therapies for VKC include immunomodulators, such as cyclosporine A and tacrolimus. Surgery is reserved for those with complications and should be handled by ophthalmologists with special expertise. Newer research on the pathogenesis of VKC is reviewed in this article. Vernal keratoconjunctivitis is a very important allergic eye disease in children. Complications and remodeling changes are unique and can lead to blindness. Understanding of pathogenesis of VKC may lead to better therapy for these unfortunate patients.

Ocular autoimmune pemphigoid and cyclosporin A.

BACKGROUND: Ocular pemphigoid is a chronic autoimmune disease that leads to vision lost. In its etiology participate autoantibodies against the connective tissue of the conjunctiva of different isotypes (IgM, IgG and IgA) as well as the complement system (C3). Lymphocytes of the CD4 + and CD8 + phenotypes and monocytes were detected in the infiltrates of the biopsies of the conjunctiva. MATERIAL AND METHODS: We treated and studied 82 patients who had several topical and systemic treatments during years to alleviate this condition but whose side effects limited their usefulness. We started the administration of cyclosporin-A (Cy-A) 100 mg/day per os and diminishing gradually the intake of steroids. The relief of ocular pain and headache were the first symptoms that changed the patients' quality of life. Ophtalmological controls revealed improvement of the lesions of the conjunctiva and cornea and subsequent biopsies showed a marked decrease in the cellular infiltrates and in antibody deposits. CONCLUSIONS: Thus, Cy-A is an useful treatment for ocular chronic autoimmune pemphigoid and eventually azathioprine (50 mg/day) can cheaply replace it although its well-known toxicity.

Inhibitory effect of a complementary peptide on ulceration in the alkali-injured rabbit cornea.

PURPOSE: Two tripeptide chemoattractants, acetyl-proline-glycine-proline (Ac-PGP) and methyl-proline-glycine-proline (Me-PGP), are the primary triggers for early neutrophil invasion into the alkali-injured cornea. In the present study the effectiveness of a complementary peptide designed to inhibit the PGP chemoattractants (arginine-threonine-arginine [RTR] tetrameric peptide) and an apo A-1 mimicking peptide (5F) was investigated in the alkali-injured rabbit eye. METHODS: (L)-RTR tetramer, (D)-RTR tetramer, and 5F were tested in vitro for their effects on neutrophil polarization. Synthetic 5F was also tested in vitro for its effect on the neutrophil respiratory burst. In the alkali-injured rabbit eye model, the right corneas of 48 rabbits were exposed to 1 N NaOH for 35 seconds. Sixteen animals were randomly assigned to each of three groups: phosphate-buffered saline (PBS) control; 800 microM RTR (dextrorotatory) tetramer in PBS alternating each hour with 1.5 mM RTR (levorotatory) tetramer in PBS; and 12 microM 5F in PBS. One topical drop of each substance was administered hourly (14 times per day) for 33 days. The experiment was continued until day 42 with no additional drops administered. RESULTS: (L)-RTR tetramer and (D)-RTR tetramer inhibited neutrophil polarization activated by the PGP chemoattractants in vitro. Synthetic 5F did not inhibit neutrophil polarization in the presence of Ac-PGP or the respiratory burst of neutrophils in the presence of a metabolic stimulant derived from alkali-degraded corneas. During the entire animal experiment, statistically fewer ulcers occurred in the RTR tetramer group than in the PBS control group (43.8% vs. 87.5%, P = 0.0046). The frequency of ulceration in the 5F group (68.8%) was not significantly different from the PBS control group. CONCLUSIONS: The reduction in the frequency of corneal ulceration by the RTR tetramer possibly resulted from its complementary binding to Ac-PGP and Me-PGP in the cornea shortly after alkali injury, leading to a reduction in the early and late infiltration of neutrophils. RTR tetramer appears to hold enough promise to warrant additional study as a therapeutic drug for the alkali-injured eye.

Cloning and expression of human corneal calgranulin C (CO-Ag).

PURPOSE: A host-parasite interaction is thought to be involved in the pathogenesis of Mooren's ulcer. We have identified a cornea-associated antigen (CO-Ag), which may be a target for the autoimmune process resulting in Mooren's ulcer. This study presents the cloning, expression, and identification of a cDNA encoding human CO-Ag. METHODS: Reverse transcription-polymerase chain reaction (RT-PCR) was performed to amplify a cDNA encoding CO-Ag in the human cornea. The cDNA fragment was cloned into a prokaryotic expression vector and the resulting plasmid was transformed into DH5 E. coli cells. Autoantibody reactivity to the CO-Ag fusion protein in patient sera was tested by Western blots. RESULTS: A cDNA encoding human CO-Ag was amplified by RT-PCR. The entire mRNA coding region was 273 nucleotides in length, predicting a 91-amino acid protein with a molecular weight of 10,683 daltons. The cDNA sequence was identical to human neutrophil calgranulin C (CaGC). Human CO-Ag was expressed in E. coli carrying a plasmid in which the CO-Ag cDNA was under control of the E. coli trc promoter. The CO-Ag fusion protein, which comprised as much as 15% of the total bacterial protein, was purified to 90% homogeneity by affinity chromatography on an immobilized metal column. The recombinant CO-Ag protein produced was recognized by autoantibodies in the sera of 6 of 15 patients with Mooren's ulcer and none of 14 normal control sera by Western blots. CONCLUSION: CO-Ag is identical to calgranulin C, a neutrophil protein found on the surface of filarial nematodes. A host-parasite interaction may cause autoimmunity to CO-Ag (CaGC) in the cornea resulting in a Mooren's ulcer.