Mutations in RPGR and RP2 account for 15% of males with simplex retinal degenerative disease.

PURPOSE: To determine the proportion of male patients presenting simplex retinal degenerative disease (RD: retinitis pigmentosa [RP] or cone/cone-rod dystrophy [COD/CORD]) with mutations in the X-linked retinal degeneration genes RPGR and RP2. METHODS: Simplex males were defined as patients with no known affected family members. Patients were excluded if they had a family history of parental consanguinity. Blood samples from a total of 214 simplex males with a diagnosis of retinal degeneration were collected for genetic analysis. The patients were screened for mutations in RPGR and RP2 by direct sequencing of PCR-amplified genomic DNA. RESULTS: We identified pathogenic mutations in 32 of the 214 patients screened (15%). Of the 29 patients with a diagnosis of COD/CORD, four mutations were identified in the ORF15 mutational hotspot of the RPGR gene. Of the 185 RP patients, three patients had mutations in RP2 and 25 had RPGR mutations (including 12 in the ORF15 region). CONCLUSIONS: This study represents mutation screening of RPGR and RP2 in the largest cohort, to date, of simplex males affected with RP or COD/CORD. Our results demonstrate a substantial contribution of RPGR mutations to retinal degenerations, and in particular, to simplex RP. Based on our findings, we suggest that RPGR should be considered as a first tier gene for screening isolated males with retinal degeneration.

Fluocinolone acetonide intravitreal sustained release device--a new addition to the armamentarium of uveitic management.

Uveitis is a potentially sight-threatening inflammatory eye disease caused by multiple infectious and non-infectious etiologies for which the standard of care involves corticosteroids or various immunomodulary therapy (IMT) drugs. These available treatments, although effective, may cause significant morbidity and sometimes mortality in uveitis patients due to their toxic side-effects and the necessity of long-term therapy to prevent recurrences. In order to avoid the systemic toxicity ofcorticosteroids and IMT or the repeated injections of local steroids necessary to control ocular inflammation, and to prevent development of cumulative damage resulting from recurrent episodes of inflammation, researchers have developed a number of local corticosteroid sustained-release devices that can be implanted directly into the vitreous of the eye, at the site of the inflammatory disease. Preliminary studies of such a device, the fluocinolone acetonide (Retisert) implant, have shown significant reductions in the number of inflammatory episodes and decreased reliance on systemic corticosteroids or other IMT. This review explores the current research evaluating the fluocinolone sustained-release intravitreal implant in the treatment of posterior uveitis and the implications for its future use on a wider scale.

The safety of intraocular ketorolac in rabbits.

PURPOSE: To assess the safety of a possible substitute treatment for intraocular steroid injections, intraocular injections of ketorolac tromethamine, one of the nonsteroidal anti-inflammatory drugs, were performed in rabbits. METHODS: Either 0.5% or 0.25% preservative-free ketorolac tromethamine ophthalmic solution (0.1 mL) was injected into the vitreous of the right eye of 15 rabbits. Physiologic saline solution (BSS; Alcon, Ft. Worth, TX) was injected into the left eye of each rabbit as a control. A standard electroretinogram and intraocular pressure measurements were obtained before injection, and repeated 1 day and 1, 2, 3, and 4 weeks after injection. After 4 weeks, the rabbits were euthanatized and the retinas examined by light and electron microscopy. Differences in the electroretinograms, intraocular pressure, and histopathology between the two eyes were recorded. Further, the elimination half-life of the drug in the vitreous was assessed. RESULTS: There were no statistically significant differences in electroretinograms, or intraocular pressure measurements obtained between the ketorolac-injected eyes and the control eyes. The half life of the drug was measured to be 2.3 hours. No histopathologic changes were observed in study eyes compared with control eyes. CONCLUSIONS: Preservative-free ketorolac tromethamine is nontoxic to the retinas of rabbits when injected intravitreally and could be considered as an alternative to intraocular steroid injections.