No abstract

Polypoidal choroidal vasculopathy (PCV) is currently recognized as a phenotype of age-related macular degeneration (AMD). PCV is believed to be a type of choroidal neovascularization, although some cases of PCV show a distinct vascular abnormality of the choroidal vessels. PCV often shows several unique clinical manifestations which are apparently different from typical neovascular AMD (tAMD). In addition, the natural course and response to treatment are often different between tAMD and PCV. Moreover, recent genetic studies suggested a possible difference in the genetic susceptibility to disease between tAMD and PCV, as well as the existence of heterogeneity among PCV cases. In viewing the accumulation of knowledge about PCV, we have summarized the recent literature regarding PCV in this review article to improve the understanding of this clinical entity including possible susceptibility genes. We will also discuss the optimal treatment strategies for PCV in accordance with the results of recent clinical and genetic studies.

relevant financial relationships. M.N. has disclosed the following relevant financial relationships: received grants for clinical research from: Alcon Japan; Otsuka Pharmaceuticals. Sobha Sivaprasad (Editor) has disclosed the following relevant financial relationships: Served as an advisor or consultant for: Allergan

To investigate whether retinal surface imaging by Cirrus high-definition optical coherence tomography (HD-OCT) clearly depicts the development process of a dissociated optic nerve fiber layer (DONFL) appearance after macular hole (MH) surgery. We reviewed the medical records of the patients who underwent MH surgery with internal limiting membrane peeling. The cases were then selected using three principal criteria: (1) surgeries performed by the same surgeon (S. K.), (2) pre- and postoperative Cirrus HD-OCT imaging, and (3) minimal follow-up of 3 months. All cases received a complete ophthalmologic examination. The presence/absence of a DONFL appearance was determined using a retinal surface image provided by Cirrus HD-OCT. Color fundus photographs were also used for determination if available. Fifteen cases met the criteria. A DONFL appearance was identified in 11 (73%) cases during the postoperative course by retinal surface imaging. A DONFL appearance was not detected in any OCT retinal surface image within the first postoperative month, gradually became distinct between 1 and 3 months after surgery, and remained detectable thereafter in all cases but one whose DONFL appearance became less detectable at 12 months. Indentations of the innermost retinal layer became apparent on cross-sectional OCT images as a DONFL appearance developed on OCT retinal surface images. There were two cases in which the DONFL appearance was not observed on color fundus photographs but detected on OCT retinal surface images. Retinal surface imaging provided by Cirrus HD-OCT appeared to be a promising option in evaluating a DONFL appearance after MH surgery.

We conducted a genome-wide association study (GWAS) on the outcome of anti-VEGF treatment for exudative age-related macular degeneration (AMD) in a prospective cohort. Four hundred and sixty-one treatment-naïve AMD patients were recruited at 13 clinical centers and all patients were treated with 3 monthly injections of ranibizumab followed by pro re nata regimen treatment for one year. Genomic DNA was collected from all patients for a 2-stage GWAS on achieving dry macula after the initial treatment, the requirement for an additional treatment, and visual acuity changes during the 12-month observation period. In addition, we evaluated 9 single-nucleotide polymorphisms (SNPs) in 8 previously reported AMD-related genes for their associations with treatment outcome. The discovery stage with 256 patients evaluated 8,480,849 SNPs, but no SNPs showed genome-wide level significance in association with treatment outcomes. Although SNPs with P-values of <5 × 10−6 were evaluated in replication samples of 205 patients, no SNP was significantly associated with treatment outcomes. Among AMD-susceptibility genes, rs10490924 in ARMS2/HTRA1 was significantly associated with additional treatment requirement in the discovery stage (P = 0.0023), and pooled analysis with the replication stage further confirmed this association (P = 0.0013). ARMS2/HTRA1 polymorphism might be able to predict the frequency of injection after initial ranibizumab treatment.

BackgroundThe effects of intravitreal ranibizumab (IVR) against exudative age-related macular degeneration (AMD) may be different associated with the lesion phenotype. This study was conducted to compare the outcomes of IVR between two different phenotypes of exudative AMD: typical neovascular AMD (tAMD) and polypoidal choroidal vasculopathy (PCV).MethodsThis is a retrospective cohort study of 54 eyes from 54 subfoveal exudative AMD patients (tAMD 24, PCV 30 eyes). Three consecutive IVR treatments (0.5 mg) were performed every month, followed by re-injections as needed. Change in the best-corrected visual acuity (BCVA) and central retinal thickness (CRT) were then compared between the tAMD and PCV groups over 12 months of follow-up.ResultsThe mean BCVA was significantly improved (-0.11 logMAR units) at month 3 after the initial IVR (p <0 .001, Wilcoxon signed-rank test), and was sustained up to 12 months in all AMD patients (p =0.02). In the subgroup analysis, the tAMD group showed a significant improvement in their mean BCVA (-0.06, -0.17, -0.15 and -0.16 logMAR units at 1, 3, 6 and 12 months, respectively), but there was only a slight but non-significant improvement in the PCV group. The improvement in the BCVA was significantly greater in the tAMD group than in the PCV group (p = 0.043, repeated measures ANOVA) over 12 months. Both phenotypes showed significant improvements in the CRT during 12 months after the initial IVR.ConclusionsIVR is an effective therapy for tAMD and PCV in the BCVA improvement in Japanese patients over 12 months of follow-up. The phenotype of tAMD showed a significantly better outcome with IVR than PCV in terms of BCVA improvement.

Both the reproducibility and imaging alignment might affect the predictive performance of the OCT parameter for postoperative visual outcome following MH surgery. The preoperative photoreceptor IS/OS defect length seems to be the most useful parameter in this regard.

BackgroundGenetic variants in the complement component 3 gene (C3) have been shown to be associated with age-related macular degeneration (AMD) in Caucasian populations of European descent. In particular, a nonsynonymous coding variant, rs2230199 (R102G), is presumed to be the most likely causal variant in the C3 locus based on strong statistical evidence for disease association and mechanistic functional evidence. However, the risk allele is absent or rare (<1%) in Japanese and Chinese populations, and the association of R102G with AMD has not been reported in Asian populations. Genetic heterogeneity of disease-associated variants among different ethnicities is common in complex diseases. Here, we sought to examine whether other common variants in C3 are associated with wet AMD, a common advanced-stage manifestation of AMD, in a Japanese population.Methodology/Principal FindingsWe genotyped 13 tag single nucleotide polymorphisms (SNPs) that capture the majority of common variations in the C3 locus and tested for associations between these SNPs and wet AMD in a Japanese population comprising 420 case subjects and 197 controls. A noncoding variant in C3 (rs2241394) exhibited statistically significant evidence of association (allelic P = 8.32×10−4; odds ratio = 0.48 [95% CI = 0.31–0.74] for the rs2241394 C allele). Multilocus logistic regression analysis confirmed that the effect of rs2241394 was independent of the previously described loci at ARMS2 and CFH, and that the model including variants in ARMS2 and CFH plus C3 rs2241394 provided a better fit than the model without rs2241394. We found no evidence of epistasis between variants in C3 and CFH, despite the fact that they are involved in the same biological pathway.ConclusionsOur study provides evidence that C3 is a common AMD-associated locus that transcends racial boundaries and provides an impetus for more detailed genetic characterization of the C3 locus in Asian populations.