To test the hypothesis that mutations in the CRB1 gene cause Leber congenital amaurosis (LCA) and, if so, to describe the ocular phenotype of patients with LCA who harbor CRB1 sequence variations. Patients: One hundred ninety probands with a clinical diagnosis of LCA were selected from a cohort of 233 probands ascertained in 5 different countries. The remaining 43 probands (18%) were excluded because they harbored sequence variations in previously identified LCA genes. Methods: One hundred ninety unrelated individuals with LCA were screened for coding sequence mutations in the CRB1 gene with single-strand conformation polymorphism analysis followed by automated DNA sequencing. Results: Twenty-one of the 190 probands (9% of the total cohort of 233) and 2 (1.4%) of 140 controls harbored amino acid-altering sequence variations in the CRB1 gene (P=.003). Conclusions: In our cohort of patients with LCA, coding sequence variations were observed in the CRB1 gene more frequently than in any of the other 5 known LCAassociated genes. Likely disease-causing sequence variations have now been identified in 64 (28%) of 233 subjects in this cohort. Clinical Relevance: Molecular diagnosis can confirm and clarify the diagnosis in an increasing fraction of patients with LCA. As genotype data accumulate, clinical phenotypes associated with specific mutations may be established. This will facilitate the counseling of patients regarding their visual prognosis and the likelihood of associated systemic anomalies.

To assess the frequency of mutations in the CRX, GUCY2D, and RPE65 genes in patients with Leber congenital amaurosis (LCA). Patients: One hundred seventy-six probands with a clinical diagnosis of LCA were from 9 countries, with the largest subgroup being 39 probands from India. Methods: Samples were screened with single-strand conformation polymorphism analysis followed by DNA sequencing of 3 genes (CRX, GUCY2D, and RPE65) known to be associated with LCA. Results: Of the 176 probands, 28 (15.9%) harbored possible disease-causing mutations. The relative contribution of each gene to the total number of mutations was as follows: CRX, 2.8%; GUCY2D, 6.3%; and RPE65, 6.8%. No patients who harbored mutations in these genes had associated systemic abnormalities. Molecular diagnosis allowed definitive genetic counseling in a family affected with Best disease and LCA. Conclusions: Molecular diagnosis may be of benefit to patients affected with LCA. The relative paucity of mutations found in this study suggests that more LCAassociated genes remain to be discovered. Clinical Relevance: Molecular diagnosis can confirm and clarify the diagnosis of LCA. As genotype data accumulate, clinical phenotypes associated with specific mutations will be established. This will facilitate the counseling of patients on their visual prognosis and the likelihood of associated systemic anomalies.

Background-Spontaneous bullous serous retinal detachment (RD) with subretinal exudation complicating idiopathic central serous chorioretinopathy (ICSC) is a rare and infrequently described clinical entity. Clinical observations are described on this variant form in 11 patients, the largest series reported to date. Methods-13 eyes of 11 Indian patients having this entity were followed up clinically and angiographically for 12-24 months (retrospective, longitudinal). None of the patients had any previous history of other diseases nor were they on any medications. Four eyes received laser treatment (group A); nine eyes were not treated (group B). Results-All

Uveitis is considered a rare complication of leptospirosis. This report describes an epidemic of uveitis among patients with leptospirosis and provides data, using polymerase chain reaction (PCR) amplification of Leptospira DNA, that the pathogenesis is associated with anterior chamber spirochetes. Forty-six uveitis patients, 49 uveitis controls, and 54 cataract controls were enrolled at Aravind Eye Hospital (Madurai, India). Leptospiral DNA was detected by PCR of aqueous humor; serum antibody titers were determined by ELISA and microagglutination (MAT). Thirty-seven uveitis patients (80%) demonstrated leptospiral DNA compared with 5 controls (8%; P < .001). Thirty-three uveitis patients (72%) had positive serology compared with 10 uveitis controls (20%) and 13 cataract controls (24%; P < .001). This report describes the largest cluster of patients with leptospiral uveitis and identifies six clinical characteristics that provide a diagnostic profile for leptospiral uveitis. This profile will be important for determining treatment regimens in countries where PCR and MAT are not available.

Aims-To describe the occurrence of spontaneous cataract absorption in patients with leptospiral uveitis. Methods-The records of patients with seropositive leptospiral uveitis seen in the uveitis clinic at Aravind Eye Hospital between January 1994 and December 1997 were reviewed retrospectively. Results-During the 4 years of the study, 394 eyes of 276 patients with seropositive leptospiral uveitis were identified. Of these, 54 eyes (13.7%) of 41 patients (14.9%) had a final visual acuity of 20/40 or worse attributable to cataract formation. Of these 54 eyes, 41 eyes (75.9%) had visually significant cataract on their first visit to the uveitis clinic, and 13 eyes (24.1%) were noted to have cataract 1-6 months after presentation. Spontaneous absorption was observed in 10 eyes (18.5%) of eight patients (19.5%), and occurred from 6 weeks to 18 months, with a median of 5 months, after the onset of cataract. Of 12 035 consecutive, non-leptospiral, nontraumatic, uveitic, control patients seen during the same 4 years of the study, none showed spontaneous cataract absorption. Conclusion-Spontaneous cataract absorption occurs in a significant number of patients with leptospiral uveitis, and appears to be unique to this form of non-traumatic uveitis.