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Objective: To determine whether genotypes at 2 major loci associated with late age-related macular degeneration (AMD), complement factor H (CFH) and age-related maculopathy susceptibility 2 (ARMS2), influence the relative benefits of Age-Related Eye Disease Study (AREDS) supplements., Design: Unplanned retrospective evaluation of a prospective, randomized, placebo-controlled clinical trial of vitamins and minerals for the treatment of AMD., Subjects: AREDS participants (mean age, 69 years) who were at risk of developing late AMD and who were randomized to the 4 arms of AREDS supplement treatment., Methods: Analyses were performed using the Cox proportional hazards model to predict progression to late AMD (neovascular or central geographic atrophy). Statistical models, adjusted for age, gender, smoking status, and baseline AMD severity, were used to examine the influence of genotypes on the response to therapy with 4 randomly assigned arms of AREDS supplement components: placebo, antioxidants (vitamin C, vitamin E, β-carotene), zinc, or a combination., Main Outcome Measures: The influence of the genotype on the relative treatment response to the randomized components of the AREDS supplement, measured as progression to late AMD., Results: Of the 1237 genotyped AREDS participants of white ethnicity, late AMD developed in 385 (31.1%) during the mean follow-up of 6.6 years. As previously demonstrated, CFH genotype (P = 0.005), ARMS2 (P< 0.0001), and supplement were associated individually with progression to late AMD. An interaction analysis found no evidence that the relative benefits of AREDS supplementation varied by genotype. Analysis of (1) CFH rs1061170 and rs1410996 combined with ARMS2 rs10490924 with the 4 randomly assigned arms of AREDS supplement and (2) analysis of the combination of CFH rs412852 and rs3766405 with ARMS2 c.372&#95;815del443ins54 with the AREDS components resulted in no interaction (P = 0.06 and P = 0.45, respectively, before multiplicity adjustment)., Conclusions: The AREDS supplements reduced the rate of AMD progression across all genotype groups. Furthermore, the genotypes at the CFH and ARMS2 loci did not statistically significantly alter the benefits of AREDS supplements. Genetic testing remains a valuable research tool, but these analyses suggest it provides no benefits in managing nutritional supplementation for patients at risk of late AMD., (Copyright © 2014 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

First syntheses of a deuterium-labeled very long C34-containing polyunsaturated fatty acid, C34:5n5.d(2), and three other unlabeled very long chain C30-32-containing polyunsaturated fatty acids are reported here. These syntheses were achieved by coupling chemically modified C22- and C20-containing polyunsaturated fatty acids with carbanions derived from arylalkyl sulfones, followed by sodium amalgam-mediated desulfonylation.

Purpose: The ocular findings, systemic features, and genetic loci distinguishing known genetic causes of vitreoretinal degenerations were studied in the original Snowflake family., Design: Prospective, comparative study and molecular genetic investigation., Participants: Members of the original snowflake vitreoretinal degeneration family., Methods: Clinical data were collected on 26 family members by history and examination. Thirteen of the 26 total family members underwent prospective examination. Linkage to known vitreoretinal degeneration loci (COL2A1, COL11A1, and the Wagner disease locus) was evaluated with short tandem repeat markers., Main Outcome Measures: Ocular and systemic features of known vitreoretinal degenerations., Results: Six of the 13 prospectively examined subjects had snowflake vitreoretinal degeneration. Corneal guttae (4/5; 80%), early onset cataract (5/6; 83%), fibrillar vitreous degeneration (6/6; 100%), and peripheral retinal abnormalities (5/6; 83%), including minute crystallinelike deposits called snowflakes (4/6; 67%), were common. Retinal detachment was seen in 1 of 6 of these prospectively examined subjects (17%). A total of 14 affected subjects were identified within the family, and in 3 (21%), retinal detachment developed. Orofacial features, early-onset hearing loss, and arthritis typical of Stickler syndrome were absent. Linkage to known vitreoretinal degeneration loci was excluded., Conclusions: The absence of vitreous gel in the retrolental space and presence of fibrillar vitreous degeneration were consistent with the vitreous structure reported for collagen 11A1 (COL11A1) but not collagen 2A1 (COL2A1) mutations. The absence of systemic features was characteristic of the vitreoretinopathies linked to chromosome 5q13 (Wagner disease and erosive vitreoretinopathy) and mutations in exon 2 of the COL2A1 gene. Snowflakes in the peripheral retina and the absence of nyctalopia, posterior chorioretinal atrophy, and tractional retinal detachment were inconsistent with the chromosome 5q13 vitreoretinopathies. The association of Fuchs' corneal endothelial dystrophy found in this family has not been reported previously in other vitreoretinal degenerations. These findings and the exclusion of known genetic loci suggest snowflake is a distinct vitreoretinal degeneration.

Purpose: To report posterior chorioretinal atrophy (PCRA) and correlate the vitreous phenotype with inheritance of the disease mutation in a family with vitreoretinal dystrophy., Design: Prospective observational case series., Methods: Twenty-four members of a family with 14 affected individuals were examined, and genetic linkage analysis was performed at the COL2A1, COL11A1, and Wagner disease loci. The vitreous phenotype was prospectively graded as optically empty with retrolenticular membrane, fibrillar, or normal. Ocular ultrasonography and optical coherence tomography (OCT) were performed on selected individuals to study the vitreous structure and vitreoretinal interface., Results: The 6-year-old proband had PCRA and optically empty vitreous without systemic features, suggestive of Wagner disease. The family history was negative for systemic disease, except for one cousin with cleft palate. However, when examined, clinical features of the 14 affected subjects included 5 with small chin, 4 with at least submucosal cleft palate, and 9 with a myopic refractive error greater than 5 diopters. Lens opacity or previous cataract extraction was found in 13 family members. All affected individuals in whom the vitreous could be examined had an optically empty vitreous with retrolental membrane. Posterior chorioretinal atrophy was found in eight of the affected subjects. The finding was not limited to highly myopic subjects, nor did all the high myopes have PCRA. Ultrasonography and OCT revealed vitreous adherent to the retina, but without apparent retinal distortion or edema of the macula. Significant linkage was established to the COL2A1 locus; the other loci were excluded. A single nucleotide insertion mutation (c.2012 2013insC) was identified in exon 34, leading to a downstream premature stop codon in the COL2A1 gene., Conclusions: Although posterior chorioretinal atrophy and vitreoretinal degeneration have been classically associated with Wagner disease, we demonstrate its presence in a family with typical Stickler syndrome. On the basis of clinical, ultrasonographic, and OCT studies, the etiology of PCRA in this family does not seem to be attributable to vitreomacular traction or myopia. The vitreous findings in this large family confirm reports that mutations in the COL2A1 gene lead to the optically empty vitreous with retrolenticular membrane phenotype.

Objective: To determine the severity of visual acuity impairment in patients, age 45 years or older, with either isolated or identifiable genetic subtypes of retinitis pigmentosa (RP) and Usher syndrome., Design: Multicenter, retrospective, cross-sectional analysis., Participants: Visual acuity data were obtained on 999 patients with different genetic subtypes of RP and Usher syndrome, age 45 years or older, from 4 major eye care centers in the United States., Intervention: The best-corrected visual acuity obtained on these patients from the eye with better vision on their most recent visit was used for the analysis., Main Outcome Measure: Best-corrected visual acuity was the main parameter analyzed for the study, and it was obtained with Snellen or Feinbloom low vision charts or with a B-VAT II monitor (Mentor)., Results: The final analyses were done on 982 patients (17 patients with a sector form of RP were analyzed separately). Of the 982 patients, 506 (52%) had a visual acuity of 20/40 or better, and 678 (69%) had a visual acuity of 20/70 or better in at least one eye. There were 243 (25%) patients who had a visual acuity of 20/200 or worse in both eyes. Five (0.5%) patients had no light perception in both eyes. The odds ratio for any patient having a visual acuity of 20/200 or worse in this population was 1.4 for each difference of 10 years of age. Similarly, the odds ratio of a patient having a visual acuity of 20/40 or better in at least one eye was 0.95 for a 10-year age difference., Conclusions: In this large population of patients with RP and Usher syndrome from four centers, it was rare for such patients to lose all vision in both eyes. One fourth of the patients had a visual acuity of 20/200 or worse in both eyes, and more than half of the population had a visual acuity of 20/40 or better in at least one eye. These data can be used to counsel such patients on the extent of potential visual acuity impairment from their disease.