Evaluation of Abicipar Pegol (an Anti-VEGF DARPin Therapeutic) in Patients With Neovascular Age-Related Macular Degeneration: Studies in Japan and the United States

BACKGROUND AND OBJECTIVE: To evaluate comparability of abicipar pegol (abicipar) effects in patients with treatment-naïve neovascular age-related macular degeneration (nAMD) in Japan and the United States. PATIENTS AND METHODS: Phase 2, multicenter, randomized, double-masked, 20-week studies (BAMBOO, Japan; CYPRESS, United States). Patients (n = 25 each study) received three monthly intravitreal injections of abicipar 1 mg or 2 mg or five monthly intravitreal injections of ranibizumab 0.5 mg. RESULTS: Mean best-corrected visual acuity change from baseline at week 16 (primary endpoint) for abicipar 1 mg, abicipar 2 mg, and ranibizumab was +7.8 letters, +8.9 letters, and +17.4 letters (BAMBOO); +4.4 letters, +10.1 letters, and +15.2 letters (CYPRESS). Mean central retinal thickness change from baseline was −187.3 μm, −196.5 μm, and −230.4 μm (BAMBOO); −106.5 μm, −112.8 μm, and −124.4 μm (CYPRESS). Uveitis or vitritis was reported in three abicipar-treated patients. CONCLUSION: Abicipar demonstrated extended duration of effect and safety that were comparable between Japanese and non-Japanese patients with nAMD. Abicipar effectively treated Japanese patients with polypoidal choroidal vasculopathy

Fundus autofluorescence of retinal angiomatous proliferation.

PurposeThe present study aimed to evaluate the characteristics of fundus autofluorescence in Japanese patients with retinal angiomatous proliferation (RAP).MethodsWe retrospectively reviewed 100 eyes from 76 patients (male, n = 45; female, n = 31; age range, 50-94 years; mean ± standard deviation, 81.4 ± 6.4 years) with treatment-naïve RAP, which was diagnosed based on the identification of retinal-retinal anastomosis on early-phase fluorescein angiography or indocyanine green angiography (ICGA) and the identification of a hot spot on late-phase ICGA. RAP was classified into the following three stages: stage 1, proliferation of intraretinal capillaries originating from the deep retinal complex (intraretinal neovascularization); stage 2, growth of the retinal vessels into the subretinal space (subretinal neovascularization); and stage 3, clinically or angiographically observed choroidal neovascularization. In all cases, short-wavelength and near-infrared autofluorescence (SW-AF, NIR-AF) was evaluated using a confocal scanning laser ophthalmoscope.ResultsThe conditions of the 100 eyes were as follows: stage 1 RAP, n = 6 (6%); stage 2 RAP without retinal pigment epithelial detachment (PED), n = 40 (40%); stage 2 RAP with PED, n = 44 (44%); and stage 3 RAP, 10 (10%). On NIR-AF imaging, the number of abnormalities that were observed to correspond to the RAP lesions on ICGA (87 eyes, 87%) was significantly greater in comparison to SW-AF imaging (27 eyes, 27%). The mean follow-up period in all 76 patients was 39.2 months. In the 76 patients with unilateral disease, 21 (21%) eyes developed RAP in the fellow eye during the follow-up period. Among 18 eyes that were examined by both SW-AF and NIR-AF imaging before the onset of RAP lesions, NIR-AF imaging showed hypoautofluorescence in 15 (83%) eyes before the onset of RAP lesions.ConclusionsSW-AF and NIR-AF abnormalities may be related to the dysfunction of the photoreceptor/retinal pigment epithelium complex. Hypoautofluorescence on NIR-AF imaging may accurately indicate the presence or onset of RAP lesions

Bilateral Serous Retinal Detachment Associated with Inferior Posterior Staphyloma Treated with Scleral Shortening and Vitrectomy

Purpose: We report a case of bilateral serous retinal detachment (SRD) associated with inferior posterior staphyloma (IPS) treated successfully with scleral shortening. Patient and Methods: A 63-year-old woman presented with bilateral visual loss due to an SRD with IPS. The best-corrected visual acuity levels were 0.6 (20/30) and 0.5 (20/40) in the right and left eye, respectively. The patient underwent vitrectomy and scleral shortening in the right eye. The lamellar scleral crescent was resected 4 mm in width from the 5- to 8-o'clock positions. Seven interrupted 5-0 polyester sutures were placed at the edge of the lamellar scleral crescent. After 25-gauge three-port vitrectomy, the sutures were tightened. Optical coherence tomography showed decreased curvature at the staphyloma border. The choroidal thickness decreased in the superior flat portion of the fundus and increased slightly in the staphyloma. The SRD resolved 3 months postoperatively. The best-corrected visual acuity in the right eye improved to 0.8 (20/25) 6 months postoperatively. Angiography 6 months postoperatively showed decreased diffuse dye leakage at the fovea in the right eye; indocyanine green angiography did not show marked changes. Discussion: Scleral shortening with vitrectomy changes the eye wall shape, may improve the retinal pigment epithelial integrity, and may be a treatment option for SRD with IPS

T: Reproducibility of retinal and choroidal thickness measurements in enhanced depth imaging and high-penetration optical coherence16. Ehrlich JR, Peterson J, Parlitsis G, Kay KY, Kiss S, Radcliffe NM: Peripapillary choroidal thickness in glaucoma measure

PURPOSE. Two optical coherence tomography (OCT) modalities can visualize the choroid: high-penetration OCT (HP-OCT) using a long wavelength, and enhanced depth imaging technique using Heidelberg OCT (EDI-OCT). The purpose of this study was to compare and investigate the agreement among the retinal/choroidal thickness parameters. METHODS. Twenty-four eyes of 12 healthy volunteers were examined simultaneously using the prototype swept-source HP-OCT and EDI-OCT. Six independent examiners measured the central retinal/choroidal thicknesses on horizontal B-scan images. The reliability was evaluated by intraclass correlation coefficient (ICC). Intervisit reproducibility was assessed by examining 10 of the volunteers 4 months later. RESULTS. Using HP-OCT, the average of all measurements was 209.1 Ϯ 12.9 m in the retina and 292.7 Ϯ 77.3 m in the choroid, and using EDI-OCT, 212.5 Ϯ 13. CONCLUSIONS. The retinal and choroidal thicknesses were wellcorrelated between the instruments. Higher reliability and reproducibility are expected for the choroidal thickness measurements despite with higher morphologic interindividual variations. (Invest Ophthalmol Vis Sci. 2011;52:5536 -5540

Fundus Autofluorescence and Optical Coherence Tomography Findings in Branch Retinal Vein Occlusion

Purpose. To describe the findings of fundus autofluorescence (FAF) and optical coherence tomography (OCT) in patients with branch retinal vein occlusion (BRVO). Methods. In this institutional, retrospective, observational case series, FAF was evaluated in 65 eyes with BRVO in 64 consecutive patients and compared with visual acuity, OCT findings, and other clinical observations. Results. Five types of autofluorescence appeared during the course of BRVO: (1) petaloid-shaped hyperautofluorescence in the area of macular edema and (2) hyperautofluorescence coincident with yellow subretinal deposits. (3) Diffuse hyperautofluorescence appeared within the area of serous retinal detachment (SRD) and OCT showed precipitates on the undersurface of the retina in 5/5 of these eyes (100%). (4) The area of vein occlusion showed diffuse hyperautofluorescence after resolution of the retinal bleeding. (5) Hard exudates exhibited hyper- or hypoautofluorescence. OCT indicated that most of the hard exudates with hyperautofluorescence were located on the retinal pigment epithelium. Conclusions. Hyperautofluorescence associated with subretinal fluid or hard exudate appeared in the subretinal space. This type of hyperautofluorescence may be attributed to blood cell or macrophages. FAF and OCT are noninvasive modalities that provide additional information regarding macular edema due to BRVO

Five-year follow-up of fundus autofluorescence and retinal sensitivity in the fellow eye in exudative age-related macular degeneration in Japan.

PURPOSE:To assess the 5-year change in abnormal fundus autofluorescence (FAF) patterns and retinal sensitivity in the fellow eye of Japanese patients with unilateral exudative age-related macular degeneration (AMD). METHODS:Patients with unilateral exudative AMD who developed abnormal FAF in the fellow eyes were enrolled. FAF imaging and microperimetry were performed at baseline and follow-ups. FAF findings were classified into 8 patterns based on the International Fundus Autofluorescence Classification Group to assess retinal sensitivity. Forty-five points covering the central 12 degrees on microperimetry were superimposed onto the FAF images. Each point was classified depending on the distance from the abnormal FAF. "Close" was defined as the portion within 1 degree from the border of any abnormal FAF, and "Distant" was defined as the portion over 1 degree from the border of abnormal FAF. To investigate the association between the retinal sensitivity and distance from the abnormal FAF, hierarchical linear mixed-effect models were used with the distance, time and time squared from baseline (months), and angle (degrees) as fixed effects. Differences among patients, eyes, and test point locations were considered successively nested random effects. RESULTS:We studied 66 fellow eyes with abnormal FAF. Twenty-seven eyes were followed-up during the 5 years. In the 13 of 27 eyes (48%), the abnormal FAF patterns had changed during the 5 years. We found retinal sensitivity was associated significantly with the distance from the abnormal FAF ("Distant": p<0.001, time2 from baseline: p<0.001, angle: p<0.001). The mean retinal sensitivity of the "Close" tended to deteriorate after the third year and eventually showed the similar sensitivity as the portion within the abnormal FAF. CONCLUSION:FAF patterns can change about half during the 5 years and the retinal sensitivity near abnormal FAF tends to deteriorate after the third year

A genome-wide association study identified a novel genetic loci STON1-GTF2A1L/LHCGR/FSHR for bilaterality of neovascular age-related macular degeneration

Bilateral neovascular age-related macular degeneration (AMD) causes much more handicaps for patients than unilateral neovascular AMD. Although several AMD-susceptibility genes have been evaluated for their associations to bilaterality, genome-wide association study (GWAS) on bilaterality has been rarely reported. In the present study, we performed GWAS using neovascular AMD cases in East Asian. The discovery stage compared 581, 252 single nucleotide polymorphisms (SNPs) between 803 unilateral and 321 bilateral Japanese cases but no SNP showed genome-wide significance, while SNPs at six regions showed P-value < 1.0 × 10[−5], STON1-GTF2A1L/LHCGR/FSHR, PLXNA1, CTNNA3, ARMS2/HTRA1, LHFP, and FLJ38725. The first replication study for these six regions comparing 36 bilateral and 132 unilateral Japanese cases confirmed significant associations of rs4482537 (STON1-GTF2A1L/LHCGR/FSHR), rs2284665 (ARMS2/HTRA1), and rs8002574 (LHFP) to bilaterality. In the second replication study comparing 24 bilateral and 78 unilateral cases from Singapore, rs4482537 (STON1-GTF2A1L/LHCGR/FSHR) only showed significant association. Meta-analysis of discovery and replication studies confirmed genome-wide level significant association (P = 2.61 × 10[−9]) of rs4482537 (STON1-GTF2A1L/LHCGR/FSHR) and strong associations (P = 5.76 × 10[−7] and 9.73 × 10[−7], respectively) of rs2284665 (ARMS2/HTRA1) and rs8002574 (LHFP). Our GWAS for neovascular AMD bilaterality found new genetic loci STON1-GTF2A1L/LHCGR/FSHR and confirmed the previously reported association of ARMS2/HTRA1