A large genome-wide association study of age-related macular degeneration highlights contributions of rare and common variants.

This is the author accepted manuscript. The final version is available from Nature Publishing Group via http://dx.doi.org/10.1038/ng.3448Advanced age-related macular degeneration (AMD) is the leading cause of blindness in the elderly, with limited therapeutic options. Here we report on a study of >12 million variants, including 163,714 directly genotyped, mostly rare, protein-altering variants. Analyzing 16,144 patients and 17,832 controls, we identify 52 independently associated common and rare variants (P < 5 × 10(-8)) distributed across 34 loci. Although wet and dry AMD subtypes exhibit predominantly shared genetics, we identify the first genetic association signal specific to wet AMD, near MMP9 (difference P value = 4.1 × 10(-10)). Very rare coding variants (frequency <0.1%) in CFH, CFI and TIMP3 suggest causal roles for these genes, as does a splice variant in SLC16A8. Our results support the hypothesis that rare coding variants can pinpoint causal genes within known genetic loci and illustrate that applying the approach systematically to detect new loci requires extremely large sample sizes.We thank all participants of all the studies included for enabling this research by their participation in these studies. Computer resources for this project have been provided by the high-performance computing centers of the University of Michigan and the University of Regensburg. Group-specific acknowledgments can be found in the Supplementary Note. The Center for Inherited Diseases Research (CIDR) Program contract number is HHSN268201200008I. This and the main consortium work were predominantly funded by 1X01HG006934-01 to G.R.A. and R01 EY022310 to J.L.H

Variability of choroidal and retinal thicknesses in healthy eyes using swept-source optical coherence tomography &ndash; implications for designing clinical trials

Albert Caramoy,1 Ludwig M Heindl2 1Eye Center Wolfsburg-Fallersleben, Wolfsburg, 2Department of Ophthalmology, University of Cologne, Cologne, Germany Aim: The aim was to study the variability of choroidal scleral interface (CSI) thickness in healthy subjects and its relevance for designing future studies. Methods: A total of 123 volunteers were imaged using swept-source optical coherence tomography. Early treatment diabetic retinopathy grid was used. Results: Mean central retinal thickness was 285.85&plusmn;14.53 &micro;m and 287.18&plusmn;12.93&nbsp;&micro;m, and mean central CSI thickness was 273.94&plusmn;77.77&nbsp;&micro;m and 271.19&plusmn;78.85&nbsp;&micro;m for the right and left eyes, respectively. Mean retinal and CSI thicknesses correlated negatively with age (p=0.023, r=&ndash;0.208 and p&lt;0.0001, r=&ndash;0.426, respectively) and axial length (p=0.016, r=&ndash;0.220 and p&lt;0.0001, r=&ndash;0.504, respectively). To detect a CSI change of at least 112&nbsp;&micro;m, a sample size of 11 or 36&nbsp;per group is needed for a single- or double-arm study, respectively (&alpha;=0.05, power =0.90, no loss to follow-up, assuming standard deviation in future studies as 100&nbsp;&micro;m). Conclusion: Future clinical studies using CSI as end point are possible with regard to sample size needed. Keywords: swept-source optical coherence tomography, choroidal thickness, retinal thickness, clinical trial

Spontaneous progression of a full-thickness macular microhole to a lamellar macular hole in spectral domain optical coherence tomography

We presented a case of full-thickness macular hole progressing into lamellar macular hole as seen in the spectral domain optical coherence tomography. Short review of the literature regarding the pathogenesis of lamellar hole was presented and discussed

Imaging tamoxifen retinopathy using spectral-domain optical coherence tomography

A case of tamoxifen retinopathy examined with spectral-domain optical coherence tomography (SD-OCT) is presented. The typical refractile deposits are located between ganglion cell layer and inner plexiform layer in SD-OCT. A defect on the outer retinal layer with disruption of the photoreceptor layer with sharp edges is seen. The still attached posterior hyaloids gives evidence of other pathomechanism involved in the outer retinal defect than that of macular hole, as suggested in the literature

Imaging tamoxifen retinopathy using spectral-domain optical coherence tomography

A case of tamoxifen retinopathy examined with spectral-domain optical coherence tomography (SD-OCT) is presented. The typical refractile deposits are located between ganglion cell layer and inner plexiform layer in SD-OCT. A defect on the outer retinal layer with disruption of the photoreceptor layer with sharp edges is seen. The still attached posterior hyaloids gives evidence of other pathomechanism involved in the outer retinal defect than that of macular hole, as suggested in the literature