Long-term characteristics of exudative age-related macular degeneration in Japanese patients.

PURPOSE: The present study aimed to evaluate the clinical characteristics of exudative age-related macular degeneration (AMD) in Japanese patients over a 10-year period and to compare the past our report. METHODS: We retrospectively reviewed 1,600 treatment-naïve patients (1,777 eyes) with exudative AMD. The 10 years were divided into 2-year phases I to V. RESULTS: Of the 1,600 patients, 720 (45.0%), 733 (45.8%), 98 (6.1%), and 49 (3.1%) were diagnosed with typical AMD, polypoidal choroidal vasculopathy (PCV), retinal angiomatous proliferation, and combined subtypes, respectively. The prevalence of PCV decreased from 54.7% in phase I to 46.0% at phase V. Of the 1,777 eyes, the mean baseline logarithm of the minimum angle of resolution best-corrected visual acuities (BCVAs) in phases I, II, III, IV, and V were 0.70, 0.66, 0.55, 0.50, and 0.48, respectively. Phases III, IV, and V had significantly (P = 0.0012, P<0.0001, P<0.0001, respectively) better baseline VAs compared with phase I. The mean lesion sizes in phases I, II, III, IV, and V were 8.6, 6.7, 5.3, 5.7, and 5.7 Macular Photocoagulation Study disc areas, respectively. The sizes were significantly (P<0.0001 for all comparisons) smaller in phases III, IV, and V compared with phase I. CONCLUSIONS: Although the prevalence of PCV decreased from 54.7% in phase I to 46.0% at phase V, PCV has nevertheless been highly prevalent in Japanese patients with AMD compared with Caucasian patients. The annual better baseline VAs and smaller lesion sizes over time might be related to development of treatment and better concerns about AMD.

RETINAL MICROSTRUCTURE IN POEMS SYNDROME.

PURPOSE: To report a 67-year-old woman with polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes (POEMS) syndrome, showing bilateral serous retinal detachment. The retinal lesion was evaluated by multimodal imaging using spectral domain optical coherence tomography and an adaptive optics (AO) camera. METHODS: A case report. RESULTS: Optical coherence tomography showed hyperreflective foci mainly in the inner retina in both eyes. The AO images showed many low-reflective dots in the right eye. Three months after hematological treatment, both hyperreflective foci in the optical coherence tomography images and the low-reflective dots in the AO images disappeared. CONCLUSION: Low-reflective dots were detected in AO images of eyes with serous retinal detachment secondary to POEMS syndrome. AO cameras can detect retinal microstructures in living eyes.

Genetic variants in pigment epithelium-derived factor influence response of polypoidal choroidal vasculopathy to photodynamic therapy.

PURPOSE: To investigate whether photodynamic therapy (PDT) outcomes of polypoidal choroidal vasculopathy (PCV) are related to baseline clinical characteristics, smoking history, or genetic factors by analyzing the retreatment-free period after the first PDT. DESIGN: Retrospective cohort study. PARTICIPANTS: The study consisted of 167 patients with PCV who underwent PDT as their first treatment. METHODS: We targeted 638 single nucleotide polymorphisms (SNPs) in 42 possible susceptible genes for age-related macular degeneration to evaluate their relation to the effectiveness of PDT for PCV. For this evaluation, we used 2 methods: (1) survival analysis, with the retreatment-free period as the target; and (2) logistic regression test between the need for additional therapy within 3 months after the first PDT and the genotypes, with age, gender, smoking status, and greatest linear dimension (GLD) at baseline as covariates. The contributions of smoking status and GLD at baseline for the retreatment-free period also were evaluated. Contributions of these factors to visual prognosis were evaluated for 1 year after PDT. MAIN OUTCOME MEASURES: Retreatment-free period after the first PDT for PCV. Secondary outcome measures included correlation of the susceptible factor to the retreatment requirement within the 3-month follow-up and the mean visual acuity change. RESULTS: In survival analyses, SERPINF1 rs12603825 showed a significant association with the retreatment-free period after the first PDT; those patients homozygous for the minor allele A of rs12603825 received additional treatment after PDT within significantly shorter times than those with other genotypes (P = 0.0038). There was no significant difference in the retreatment-free period between baseline GLD and smoking status. Retreatment within 3 months was required significantly more in patients with the AA genotype, even after taking into consideration the effect of clinical characteristics (age, gender), baseline PCV lesion size, and smoking status (P = 0.0027). Furthermore, patients with the AA genotype showed significantly worse visual prognosis after PDT (P = 0.013). CONCLUSIONS: Pigment epithelium-derived factor (SERPINF1 or PEDF) polymorphisms may influence the initial response to and visual prognosis after PDT for PCV. Our findings may lead to understanding the pathogenesis of PCV and modification of the effects of PDT.

Infrared fundus autofluorescence and central serous chorioretinopathy.

PURPOSE: To investigate the findings of infrared fundus autofluorescence in eyes with central serous chorioretinopathy (CSC). METHODS: This study was an observational follow-up of 83 eyes of 80 consecutive patients with CSC recruited from a hospital referral practice. Infrared autofluorescence (IR-AF) findings and those of other clinical studies, including short-wave autofluorescence (SW-AF), fundus color photography, and optical coherence tomography were assessed. The IR-AF changes that appeared during the follow-up period were recorded. The relationship between IR- and SW-AF was analyzed by comparing the categories of focal autofluorescence (granular hyper-AF, granular hypo-AF, and mixed AF). The influence of final clinical findings on final best corrected visual acuity (BCVA) was analyzed. RESULTS: Twenty-three of 83 (27%) eyes showed granular hyper-IR-AF, whereas 53 (64%) eyes showed granular hyper-SW-AF. Most of the eyes with granular hyper-IR-AF (92%) showed granular hyper-SW-AF. On the contrary, the eyes with granular hyper-SW-AF showed various patterns of IR-AF. The deposits with hyper-IR-AF corresponding to hyper-SW-AF turned into hypo-IR-AF with hyper-SW-AF in four eyes. Final BCVA was significantly worse in eyes with granular hypo-IR-AF compared with the eyes without the findings (P = 0.035). CONCLUSIONS: Granular hyper-IR-AF from the deposits in CSC appeared concurrently with hyper-SW-AF. Granular hyper-IR-AF changed from hyperautofluorescence to hypoautofluorescence during the follow-up period. This change of IR-AF characteristics was different from that of SW-AF. The changes are attributable to the modification of melanin in the RPE. The authors speculate that the lipofuscin-like materials contribute to the characteristic changes of IR-AF through the modification of melanin in the RPE.

CCR3 is a target for age-related macular degeneration diagnosis and therapy.

Age-related macular degeneration (AMD), a leading cause of blindness worldwide, is as prevalent as cancer in industrialized nations. Most blindness in AMD results from invasion of the retina by choroidal neovascularisation (CNV). Here we show that the eosinophil/mast cell chemokine receptor CCR3 is specifically expressed in choroidal neovascular endothelial cells in humans with AMD, and that despite the expression of its ligands eotaxin-1, -2 and -3, neither eosinophils nor mast cells are present in human CNV. Genetic or pharmacological targeting of CCR3 or eotaxins inhibited injury-induced CNV in mice. CNV suppression by CCR3 blockade was due to direct inhibition of endothelial cell proliferation, and was uncoupled from inflammation because it occurred in mice lacking eosinophils or mast cells, and was independent of macrophage and neutrophil recruitment. CCR3 blockade was more effective at reducing CNV than vascular endothelial growth factor A (VEGF-A) neutralization, which is in clinical use at present, and, unlike VEGF-A blockade, is not toxic to the mouse retina. In vivo imaging with CCR3-targeting quantum dots located spontaneous CNV invisible to standard fluorescein angiography in mice before retinal invasion. CCR3 targeting might reduce vision loss due to AMD through early detection and therapeutic angioinhibition.

ARMS2 (LOC387715) variants in Japanese patients with exudative age-related macular degeneration and polypoidal choroidal vasculopathy.

PURPOSE: To determine the characteristics of the polymorphisms in the ARMS2 gene in Japanese patients with age-related macular degeneration (AMD) and those with polypoidal choroidal vasculopathy (PCV) and in healthy controls, and also to show possible associations of the polymorphisms with the disease. DESIGN: Case-control association study. METHODS: Fifty-six unrelated Japanese individuals with AMD, 55 with PCV, and 77 controls were studied. The most common polymorphism in the ARMS2 gene on chromosome 10 was resequenced. Association tests were performed for inferred haplotypes. RESULTS: A total of 22 polymorphisms were identified, and 13 were shared with those in White persons with AMD. The sequence of the deletion-and-insertion polymorphism, de1443ins54, a functional polymorphism causing an instability of the messenger ribonucleic acid of ARMS2 in the Japanese, did not differ from that in White persons. Among the polymorphisms seen in the White population, rs10490923 (R3H) as well as 7 other polymorphisms were not observed in the Japanese. One haplotype, which contained the T allele of the rs10490924 (A69S) and the variant of de1443ins54 polymorphism, had an odds ratio of 3.14 (P = 7.8 x 10(-6)) for AMD and 2.00 (P = .0058) for PCV. Among the 9 polymorphisms that were unique to the Japanese population, 2 had a minor allelic frequency of more than 0.05, and these 2 polymorphism were included as nonrisk haplotypes. CONCLUSIONS: The de1443ins54 polymorphism is a common variant between White and Japanese populations. It is strongly associated not only with AMD but also with PCV.

Absence of association between COL1A1 polymorphisms and high myopia in the Japanese population.

PURPOSE: The collagen type I alpha 1 (COL1A1) gene was recently reported to be associated with high myopia in the Japanese population. To validate this positive association, the tag single-nucleotide polymorphism (tSNP) approach was used. METHODS: Eight tSNPs, including rs2075555 and rs2269336 (previously reported to be high myopia-susceptible SNPs in the Japanese), were selected to tag the linkage disequilibrium blocks harboring the COL1A1. These tSNPs were genotyped by using an SNP assay. A total of 427 unrelated Japanese cases with high myopia (axial length, >or=26.50 mm in both eyes; the refraction of the 644 phakic eyes ranged from -5.0 to -36.0 D, with a mean +/- SD of -13.61+/-4.20 D) and 420 Japanese control subjects were recruited. Genotype and allele distributions were compared between the cases and controls by using the chi(2) test, with multiple testing corrections performed by the permutation test. RESULTS: There was no association noted between high myopia and rs2075555 (P=0.47, P(c)>0.99) and rs2269336 (P=0.40, P(c)>0.99). Meta-analysis of a previous Japanese study and new data obtained in a fixed-effect model indicated a mild significant association of high myopia with rs2075555 (odds ratio [OR], 1.19; 95% confidence interval [CI], 1.03-1.38, P=0.022) and rs2269336 (OR, 1.18; 95% CI, 1.02-1.36, P=0.026). No significant associations were seen with further tSNPs tests. CONCLUSIONS: This study did not replicate the previously reported positive association between COL1A1 and high myopia in the Japanese population, and thus the genetic risk associated with this gene, if any, is weaker than originally reported.

Clinical characteristics of exudative age-related macular degeneration in Japanese patients.

PURPOSE: To clarify the clinical characteristics of exudative age-related macular degeneration (AMD) in Japanese patients. DESIGN: Retrospective, observational, consecutive case series. METHODS: Two hundred and eighty-nine patients with neovascular AMD were examined. RESULTS: The authors classified the patients into three subtypes of neovascular AMD: polypoidal choroidal vasculopathy (PCV), retinal angiomatous proliferation (RAP), and typical AMD. One hundred and fifty-eight patients (54.7%) were diagnosed with PCV and 102 patients (35.3%) with typical AMD. RAP was observed in 13 patients (4.5%). In 16 patients (5.5%), one eye had PCV and the other eye had typical AMD. Most patients with PCV and typical AMD had unilateral disease (81.6% and 94.1%, respectively) with a male preponderance (77.8% and 71.6%, respectively). Nine of 13 patients with RAP were female (69.2%). Patients with RAP were older (mean, 80.3 years for men and 75.3 years for women) than patients with other subtypes. Serous and hemorrhagic pigment epithelial detachment developed in 69 patients (43.7%) with PCV, 22 patients (21.6%) with typical AMD, and nine patients (69.2%) with RAP. In the patients with unilateral disease in each subtype, large drusen in the unaffected eye were seen in 24.0% with PCV, 30.2% with typical AMD, and 77.8% with RAP. CONCLUSIONS: Neovascular AMD in Japanese patients has different demographic features compared with that in White patients. In Japanese patients, there is a preponderance of PCV, male gender, unilaterality, and absence of drusen in the second eye, with the exception of RAP.