Evaluation of KIR3DL1/KIR3DS1 polymorphism in Behçet's disease.

The Behçet's disease (BD)-associated human leukocyte antigen (HLA) allele, HLA-B*51 (B*51), encodes a ligand for a pair of allelic killer immunoglobulin-like receptors (KIR) present on cytotoxic cells-KIR3DL1, which inhibits their cytotoxicity, and KIR3DS1, which activates their cytotoxic activity. We tested whether KIR-regulated mechanisms contribute to BD by testing for association of KIR3DL1/KIR3DS1 genotypes with disease in 1799 BD patients and 1710 healthy controls from Turkey, as well as in different subsets of individuals with HLA-type-defined ligands for the KIR3D receptors. HLA types were imputed from single nucleotide polymorphism genotypes determined with the Immunochip. The presence of inhibitory KIR3DL1 or activating KIR3DS1 alleles did not differ significantly between cases and controls (KIR3DL1: 92.9% vs 93.4%, Pdominant=0.55; KIR3DS1: 42.7% vs 41.0%, Pdominant=0.29). The KIR3DL1/KIR3DS1 alleles were also present at similar frequencies among cases and controls bearing HLA-B with a Bw4 motif; HLA-B with a Bw4 motif with isoleucine at position 80; and HLA-B*51. Our results suggest that pathogenic mechanisms associated with HLA-B*51 do not primarily involve differential interactions with KIR3DL1 and KIR3DS1 receptors. However, due to the complexity of this locus (that is, sequence variation and copy number variation), we cannot exclude a role for other types of KIR variation in the pathogenesis of BD.

Cyclosporine for Behçet's uveitis: is it associated with an increased risk of neurological involvement?

OBJECTIVE: The immunosuppressant cyclosporine is widely used to treat Behçet's disease (BD). The aim of this study was to determine whether cyclosporine increases the risk of neurological involvement in BD. METHODS: Patient files from the Ophthalmology Department for the period 2000-2005 were screened retrospectively, and the occurrence of neurological involvement and its relationship to ocular severity were evaluated. RESULTS: A total of 454 patients with BD were seen at the Ophthalmology Department in this period, including 24 who had been referred from the Neurology Department. Excluded from the study were 47 patients who did not have uveitis and 114 patients with an inadequate follow-up. The remaining 269 patients had been treated with either cyclosporine (Group I, n=92), other immunosuppressants (Group II, n=132), or no treatment other than colchicine (Group III, n=45). Patients with neurological symptoms were sent to the Neurology Department for evaluation: 20 from Group I [10 with primary headache, 1 with depression, 1 with sinus thrombosis, and 8 with parenchymal neurological involvement (pNBD)]; 13 from Group II [10 with primary headache, 1 with pre-morbid epilepsy, 1 with sinus thrombosis, and 1 with pNBD]; and 5 from Group III with primary headache. The frequency of pNBD was significantly higher in Group I, and included atypical features such as seizures and MRI lesions as well as the typical symptoms of brainstem involvement and pleocytosis. Eye involvement tended to be more severe in Group I, and the difference remained significant both when milder cases were excluded from the analysis (6 vs. 0; p=0.03) and when severe cases were excluded (p=0.04). pNBD was significantly more frequent in patients on cyclosporine alone than in those receiving cyclosporine plus another agent. CONCLUSION: In patients with Behçet's uveitis, cyclosporine seems to be associated with an increased risk of developing pNBD, although the reason for this is unknown. A prospective trial is needed to shed light on this problem.

Clinical course of ocular Behçet's disease in siblings.

PURPOSE: Familial occurrence has been reported in approximately 8% of Turkish patients with Behçet's disease. Our aim was to compare the clinical course of ocular Behçet's disease among siblings. METHODS: We retrospectively studied five pairs of siblings with ocular involvement of Behçet's disease. No other family member of these siblings had any symptom of Behçet's disease. RESULTS: The siblings comprised three sister-brother pairs, one sister-sister pair, and one brother-brother pair. There was a 5-10-year difference between the age at onset of ocular disease among siblings. Three of the five pairs (two sister-brother, one brother-brother) had a dissimilar course of disease activity. Female siblings had an earlier age at onset and tended to have a worse prognosis than their brothers. CONCLUSIONS: It is generally acknowledged that male sex is associated with a worse prognosis. In this study, however, we observed that, among siblings with a dissimilar course, female patients were more severely affected than male patients. Poor ocular prognosis in a patient does not indicate aggressive treatment in his/her sibling. We believe that each sibling should be managed on an individual basis.

Lack of association of HLA-B*51 with a severe disease course in Behçet's disease.

OBJECTIVE: To investigate the previously reported association of HLA-B51 with the manifestations and severity of Behçet's disease (BD). METHODS: The study group consisted of 148 consecutive BD patients (89 male, 59 female) with a minimum disease duration of 5 yr followed up at an out-patient BD clinic in a tertiary referral centre. The patients were classified into three severity groups (mild, moderate, severe) using a modified form of the BD total activity index. HLA-B alleles were determined by DNA amplification using the polymerase chain reaction and sequential hybridization with sequence-specific oligonucleotide probes. RESULTS: The frequencies of genital ulceration [odds ratio (OR)=3.1, 95% confidence interval (CI) 1.3-7.5], skin findings (erythema nodosum, folliculitis or acne-like lesions) (OR=4.4, 95% CI 1.1-17.7), a positive skin pathergy test (OR=3.4, 95% CI 1.1-10.9) and eye disease (OR=1.8, 95% CI 0.9-3.7) were all higher in B*51-positive patients. By contrast, no significant association was observed between B*51 positivity and a severe disease course, and B*51 homozygosity did not exhibit a prominent association with the severity of BD. Male sex was found to be the strongest determinant of the severity of BD by logistic regression analysis (OR=4.7, 95% CI 1.9-11.2). CONCLUSION: HLA-B*51 does not exhibit a strong association with a more severe disease course in BD. The involvement of other genetic and/or environmental factors seems to be required and to be more important than B*51 for the progression of BD.

Cytomegalovirus retinitis in a patient with Wegener's granulomatosis.

Cytomegalovirus retinitis (CMVR) is a rare complication of systemic immunosuppressive therapy in patients with rheumatic disorders. We describe a 44-year-old man with Wegener's granulomatosis who was treated with cyclophosphamide and methylprednisolone and who subsequently developed bilateral CMVR. In spite of discontinuation of immunosuppressive therapy and administration of systemic ganciclovir, retinitis recurred and maintenance therapy was needed. In conclusion, increased awareness of this potentially serious complication of immunosuppressive therapy is critical. If immune recovery is slow after discontinuation of immunosuppressive agents, prolonged antiviral therapy is required in order to prevent recurrences of CMVR.

Long-term follow-up of patients with atopic keratoconjunctivitis.

OBJECTIVE: This study aimed to review the presenting features, treatment administered to, histopathologic findings, and complications encountered in a cohort of patients with atopic keratoconjunctivitis. DESIGN: The study design was a retrospective cohort series. PARTICIPANTS: The medical records of 20 patients with atopic keratoconjunctivitis and a minimum follow-up of 3 years were reviewed. MAIN OUTCOME MEASURES: Conjunctival and corneal complications, visual acuity before and after surgery, and histopathologic features on conjunctival biopsy were measured. RESULTS: Significant keratopathy developed in 70% of patients, corneal neovascularization in 60%, fornix foreshortening in 25%, and symblepharon in 20% during the course of their disease. Eleven patients (12 eyes) required penetrating keratoplasty (3 for tectonic purposes and 8 for visual rehabilitation). Vision improved by four or more lines of Snellen acuity in four eyes, improved by two lines in two eyes, remained the same in five eyes, and worsened by two lines in one eye after keratoplasty. Cataract surgery was performed in seven patients (nine eyes) with vision improving by four or more lines in six patients (eight eyes). CONCLUSION: Atopic keratoconjunctivitis is a potentially blinding disease that may result in a poor visual outcome as a result of corneal complications. Elective surgical intervention may be of benefit and can be considered in those patients whose inflammation is well controlled.

An experimental study on the effect of collagen shields and therapeutic contact lenses on corneal wound healing.

We evaluated the effects of collagen shields and therapeutic contact lenses on corneal wound healing in rabbits. A corneal wound was created by mechanical removal of the central 6-mm zone of the corneal epithelium and basement membrane in 30 eyes of 15 rabbits. The animals were divided into three groups: five rabbits in the first group were treated with a collagen shield in one eye and a therapeutic lens in the other eye. In the remaining two groups, either a collagen shield or a therapeutic lens was applied in one eye and the other eye served as the control. The radius and area of the wound were measured at 0, 6, 24, and 48 h after wounding. Linear regression analysis revealed a significant reduction in the wound area with time in all groups. The healing rate was found to be 0.52 +/- 0.08 mm2/h in the collagen shield, 0.54 +/- 0.05 mm2/h in the therapeutic lens, and 0.43 +/- 0.06 mm2/h in the control group. Comparison of the study groups by Bonferroni modification of analysis of variance revealed no statistically significant difference between the collagen shield and the therapeutic lens group at any time (p > 0.05), whereas a significantly larger wound size was observed in the control group compared with the treatment groups at all times studied (p < 0.05 at 6 h; p < 0.001 at 24 and 48 h). In conclusion, our results indicate that both collagen shields and therapeutic lenses enhance wound healing in rabbit eyes.

Changing patterns in uveitis of childhood.

BACKGROUND: Although uveitis is relatively uncommon in children, its diagnosis and management present a distinct clinical challenge for the physician. An improved knowledge of disease patterns and associated morbidity will help in the care of children with uveitis. METHODS: The authors reviewed the records of 130 patients with onset of uveitis at 16 years of age or younger. The etiology of uveitis, complications encountered, treatment administered, and visual results were analyzed. RESULTS: Uveitis associated with juvenile rheumatoid arthritis (JRA) was the largest group (41.5%) followed by idiopathic uveitis (21.5%) and pars planitis (15.3%). Twenty-six percent of the eyes had less than 20/200 visual acuity at the time of first referral. Patients with JRA had the highest rate of complications: cataract (71%), glaucoma (30%), band keratopathy (66%), and hypotony (19%). The most frequent complication of pars planitis was maculopathy (55%). Final visual acuity was less than 20/200 in 26% of eyes with JRA, 10.5% with pars planitis, and 14% with idiopathic uveitis. CONCLUSION: Uveitis beginning in childhood is a serious disease associated with sight-threatening complications. Juvenile rheumatoid arthritis-associated uveitis remains a leading cause of ocular morbidity in patients with childhood uveitis. Increased awareness by pediatricians, rheumatologists, and ophthalmologists of the seriousness of ocular complications of uveitis in childhood may lead to earlier diagnosis and more effective treatment regimens in the future.

Penetrating keratoplasty in atopic keratoconjunctivitis.

Penetrating keratoplasty (PK) may be required for visual rehabilitation or tectonic purposes in patients with severe keratopathy due to atopic keratoconjunctivitis (AKC). The outcome of PK is often poor in such patients because of adnexal and ocular surface abnormalities. We studied nine AKC patients requiring PK and evaluated the visual outcome and prognostic factors in 11 eyes. The mean follow-up was 87.2 months (range, 30-180 months). Preoperatively all patients had visual acuity of hand motion to 20/200. Eighteen grafts were performed. Final visual acuity was 20/40 or better in 46% of the eyes. Ten eyes retained clear grafts and improved an average of 4.5 Snellen acuity lines.

Immunopathologic study of the conjunctiva in patients with behçet disease.

PURPOSE: Even though conjunctiva is not primarily involved in patients with uveitis due to Behçet disease, it may reflect the immunopathologic process when inflammation is induced by biopsy of conjunctiva, a phenomenon similar to the induced inflammation at skin pathergy sites. METHODS: Conjunctival biopsy specimens obtained 48 hours after a 2-mm biopsy of the epibulbar conjunctiva in 26 Turkish patients with inactive ocular Behçet disease and 9 Turkish patients with inactive idiopathic uveitis were studied by immunoperoxidase using a panel of monoclonal antibodies: anti-CD1, -CD3, -CD4, -CD5, -CD14, -CD22, -CD25, and -CD67, HLA-DR, E-selectin, intercellular adhesion molecule-1 (ICAM-1), and vascular cell adhesion molecule-1 (VCAM-1). RESULTS: Immunopathology of the conjunctival specimens obtained at the time of first biopsy was not significantly different between the Behçet disease and the idiopathic uveitis groups. The second-biopsy specimens of the patients with Behçet disease showed significantly greater numbers of T cells (CD3+, CD4+) and granulocytes (CD67+) as well as HLA-DR+ and ICAM-1+ cells in the substantia propria. Vascular endothelium of the conjunctiva in a patient with Behçet disease had significantly more pronounced expression of the adhesion molecules, E-selectin, and ICAM-1. None of the conjunctival specimens in either group showed VCAM-1 positivity. CONCLUSIONS: These results show that a more intense antigen-independent inflammation develops with recruitment of both neutrophils and T lymphocytes of helper/ inducer phenotype in the conjunctiva of patients with Behçet disease in response to surgical trauma. Increased expression of E-selectin and ICAM-1 in the conjunctiva of patients with Behçet disease may suggest a critical role for these adhesion molecules in the initial events of inflammation.

Penetrating keratoplasty in cicatrizing conjunctival diseases.

PURPOSE: The outcome of successful penetrating keratoplasty (PK) typically is poor in eyes with end-stage chronic cicatrizing conjunctival diseases such as ocular cicatricial pemphigoid (OCP), Stevens-Johnson syndrome, and toxic epidermal necrolysis due to immunologically driven conjunctival inflammation associated with conjunctival cicatrization and lid abnormalities, severe dry eye, and extensive corneal neovascularization. The authors report the results of their experience with PK in 13 patients with OCP, Stevens-Johnson syndrome, and toxic epidermal necrolysis. METHODS: The authors reviewed the records of patients with OCP, Stevens-Johnson syndrome, or toxic epidermal necrolysis seen between 1976 and 1992. Patients who underwent PK were examined for the purpose of this study. Initial and final visual acuity, indications for PK, surgical procedure, postoperative therapy, complications, total number of repeat PKs, length of follow-up, and the final outcome were recorded. RESULTS: Thirty-two PKs were performed in 16 eyes of 13 patients with advanced OCP (6 patients), OCP as a sequela of Stevens-Johnson syndrome (2 patients), Stevens-Johnson syndrome (3 patients), and toxic epidermal necrolysis (2 patients). The indications for the first PK were corneal perforation in six eyes (37.5%) and extensive corneal scarring in ten eyes (62.5%). Preoperative visual acuity was counting fingers in five eyes, hand motions in eight, and light perception in three. Preoperative therapy included systemic chemotherapy (8 patients), mucous membrane grafting (9 eyes), lamellar keratoplasty (2 eyes), superficial keratectomy (1 eye), and corneal dye laser photocoagulation (6 eyes). The mean follow-up period was 4.6 years (3 months-13 years). Eight eyes (50%) had clear grafts, and three eyes (18.7%) had 20/200 or better visual acuity at last visit. The major causes of graft failure were epithelial defect formation/persistence, stromal ulceration, perforation, and graft rejection. CONCLUSIONS: These results indicate that PK may be performed for tectonic reasons, but prospects for restoration of sight in patients with advanced cicatrizing conjunctival diseases, even after extensive preoperative medical and surgical therapy, are limited.

Corneal sensitivity after penetrating keratoplasty.

In order to determine corneal sensitivity after penetrating keratoplasty, 71 corneal transplants and their recipient beds were tested using the Cochet-Bonnet esthesiometer. The periods from surgery to examination were two weeks to 15 years. When the test results were divided into six groups according to the postoperative period, correlation analysis revealed a progressive improvement of sensitivity in the central and peripheral graft as well as in the recipient cornea. Only one graft had normal central sensitivity at 24 months; 36 grafts were completely anesthetic while 35 grafts had some level of sensitivity at the time of last clinical testing. Age, preoperative diagnosis or graft size were not correlated with the recovery of sensitivity. The extent and time of reinnervation in corneal grafts varied in individual patients.

Binocular vision regained after monocular traumatic aphakia by wearing contact lenses.

In this study 35 patients with monocular traumatic aphakia were enrolled to document the degree of binocular vision gained by optical correction with contact lenses. The most important factors in achieving binocular vision were the interval between formation of the traumatic cataract and surgery and between the operation and starting wearing contact lenses. There was a statistically significant correlation between these two intervals and the achievement of near stereopsis and normal visual acuity.