Defects in the Cell Signaling Mediator ß-Catenin Cause the Retinal Vascular Condition FEVR.

Familial exudative vitreoretinopathy (FEVR) is an inherited blinding disorder characterized by the abnormal development of the retinal vasculature. The majority of mutations identified in FEVR are found within four genes that encode the receptor complex (FZD4, LRP5, and TSPAN12) and ligand (NDP) of a molecular pathway that controls angiogenesis, the Norrin-ß-catenin signaling pathway. However, half of all FEVR-affected case subjects do not harbor mutations in these genes, indicating that further mutated genes remain to be identified. Here we report the identification of mutations in CTNNB1, the gene encoding ß-catenin, as a cause of FEVR. We describe heterozygous mutations (c.2142_2157dup [p.His720∗] and c.2128C>T [p.Arg710Cys]) in two dominant FEVR-affected families and a de novo mutation (c.1434_1435insC [p.Glu479Argfs∗18]) in a simplex case subject. Previous studies have reported heterozygous de novo CTNNB1 mutations as a cause of syndromic intellectual disability (ID) and autism spectrum disorder, and somatic mutations are linked to many cancers. However, in this study we show that Mendelian inherited CTNNB1 mutations can cause non-syndromic FEVR and that FEVR can be a part of the syndromic ID phenotype, further establishing the role that ß-catenin signaling plays in the development of the retinal vasculature.

Time dependent effects of sympathetic denervation on aqueous humor dynamics and choroidal blood flow in rabbits.

PURPOSE: This study investigates the time-dependent effects of superior cervical ganglionectomy (SCGx) on aqueous humor dynamics and ocular blood flow in rabbits. METHODS: Measurements were made at various times between 24 hours and 12 months after SCGx. Intraocular pressure (IOP) was measured by pneumatonometry, aqueous flow by fluorophotometry and outflow facility by tonography. Uveoscleral outflow was determined by an intracameral tracer infusion technique and blood flow to the choroid was evaluated with fluorescent microspheres. Values in denervated eyes were compared with the contralateral, normally-innervated eyes using a paired Student's two-tailed t-test. RESULTS: At 24 hours after SCGx, IOP in denervated eyes was less than in normally-innervated eyes (14.6 +/- 0.8 vs 20.1 +/- 1.5 mmHg, 27%, p < 0.002). At one month, IOPs were not different between eyes. Compared with normally-innervated eyes at 10-12 months, IOP in denervated eyes was greater (20.4 +/- 0.7 vs 17.2 +/- 0.9 mmHg, 19%, p < 0.001), outflow facility was less (0.15 +/- 0.02 vs 0.21 +/- 0.01 microl/min/mmHg, 29%, p < 0.01) and blood flow to the choroid was less (12.1 +/- 5.0 vs 16.2 +/- 6.0 ml/min/gm tissue, 25%, p < 0.05). Aqueous humor flow was not significantly altered by SCGx at any time. CONCLUSIONS: The reduction in IOP at 24 hours after SCGx was not due to any change in aqueous flow or uveoscleral outflow (current study) but rather to an increase in outflow facility (previous studies). At 10-12 months, IOP was elevated because outflow facility was significantly reduced. The reduction in choroidal blood flow at 10-12 months may have occurred because of the increased IOP.

Visual outcomes of silicone oil versus gas tamponade for macular hole surgery.

PURPOSE: To determine the effectiveness of silicone oil versus gas tamponade to treat macular holes. METHODS: A retrospective review of patients who underwent macular hole repair with either silicone oil or gas tamponade. RESULTS: Data collected from 66 eyes from a retina only practice (Retina and Vitreous of Texas) were reviewed to assess visual outcomes of surgery with silicone oil versus 14% C3F8 gas tamponade. 21 eyes were non-randomized to silicone oil tamponade and 45 eyes underwent gas tamponade. The average overall follow-up time was 11.8 months. Stage 2 holes constituted 9% of the holes; stage 3 and 4 made up 75%; recurrent holes were 11%; and 5% were traumatic holes. Of the macular holes not treated previously, 81.3% (13 of 16) were sealed successfully with silicone oil tamponade while 83.7% (36 of 43) of the gas-treated eyes were sealed. The overall primary closure rate was 83.1% (49 of 59). The pre-operative decimal visual acuity was 0.104 (20/192) for the silicone oil group and 0.193 (20/104) for the gas-treated group. The post-operative decimal visual acuity at 1 year was 0.208 (20/96) for the silicone oil group and 0.453 (20/44) for the gas-treated group. The reopening rate for the silicone oil group was 14% (3 of 21) and 9% (4 of 45) for the gas-treated group. The need for cataract surgery post macular hole repair was 36% (4 of 11 phakic patients) for the silicone oil group and 61% (17 of 28 phakic patients) for the gas-treated group. CONCLUSIONS: With short-term follow-up silicone oil tamponade and gas tamponade are both successful in anatomic closure of macular holes. In eyes with macular holes surgically repaired with gas tamponade significant improvements in visual acuity are seen more frequently than eyes treated with silicone oil tamponade. Toxicity of silicone oil to the retinal pigment epithelium and/or photoreceptors may play a role in these results.