Glaucomatous changes in lamina pores shape within the lamina cribrosa using wide bandwidth, femtosecond mode-locked laser OCT.

PURPOSE: The lamina cribrosa (LC) is known to play a critical role in the pathogenesis of glaucoma. Although it has been reported that striae-shaped or slit-shaped lamina pores are more frequent in eyes with primary open angle glaucoma (POAG), this observation is based only on fundus photography. The primary object of this study is to perform layer-by-layer comparisons of the shape of lamina pores within the LC in vivo. DESIGN: Cross-sectional study. METHODS: Optic nerve head B-scans were obtained using custom-made broad-wavelength optical coherence tomography with a mode-locked laser. A total of 300 single B-scans per eye were obtained and three-dimensional images were rendered from these image sequences to obtain 2-µm thin-slice en face images of the LC. Elongation indices (EIs) of the lamina pores were measured from the anterior surface (AS) of the LC to the deeper layers in 40-µm increments. RESULTS: Thirteen eyes from 10 primary open angle glaucoma (POAG) patients of mean deviation -15.2 (-16.5, -12.9) (median [25,75 percentile]) dB and 10 eyes from 7 normal controls were studied. Although the EI value was not significantly different between the superior, temporal and inferior regions of the LC at any depth level in either group, it was greater at the AS than at the 40 µm and 80 µm depth levels (P < .001) in both groups, and was greater in the POAG group only at the AS and 40 µm depth level (P ≤ .05). After adjustment for age and refraction, the effects of depth and presence of POAG on the EI value remained significant. Also, the severity of glaucoma and depth were significant factors associated with EI in multivariate analysis. CONCLUSIONS: Elongation of lamina pores was significantly more evident at the anterior surface and the 40-µm depth level of the LC in POAG eyes than in normal eyes, suggesting that nerve fiber bundles passing through the LC were under greater stress in the anterior layers of the LC.

Vertical asymmetry of lamina cribrosa tilt angles using wide bandwidth, femtosecond mode-locked laser OCT; effect of myopia and glaucoma.

PURPOSE: Morphological features of the lamina cribrosa (LC) and optic disc may be important in the pathogenesis of glaucoma and myopic neuropathy. We therefore performed a cross-sectional study of patients with glaucoma and myopic neuropathy to evaluate vertical asymmetry of LC tilt angles (LCTAs) from Bruch's membrane opening (BMO). MATERIAL AND METHODS: Forty-six control eyes and 35 primary open-angle glaucoma (POAG) eyes were included. A raster scanning protocol with 300 single B-scans (without averaging) were obtained using optical coherence tomography with a wide-bandwidth, femtosecond mode-locked (ML) laser. Superior temporal to inferior nasal (ST) direction and inferior temporal to superior nasal (IT) direction (±45° rotation with a horizontal line) lines were drawn, and the angle between the inner edge of the BMO plane and the best fitting line for the anterior LC plane was measured as the LCTA. The generalized estimating equation was used to analyze the eye-derived data. RESULTS: Although no significant differences in either ST-LTCAs or IT-LTCAs were observed between the glaucoma group and non-glaucoma group, the IT-LCTAs were found to be significantly greater than the ST-LCTA in both the glaucoma and non-glaucoma groups (P < 0.001). After adjustment for other potential confounding factors by multivariate analysis, greater refractive errors were significantly correlated with IT-LCTAs. CONCLUSIONS: Vertical asymmetry of the LC tilting from the BMO plane exists in both normal and POAG eyes, and correlates with the degree of myopia.

Generation of broadband noise-like pulse from Yb-doped fiber laser ring cavity.

We have demonstrated a generation of the noise-like pulse (NLP) with broadband spectrum in a nonlinear polarized evolution-based passive mode-locked Yb-doped fiber (YDF) ring laser. At the cavity dispersion of near zero, the NLP with spectrum bandwidth up to 131 nm (FWHM) was obtained at a central wavelength of 1070 nm with output power of 136 mW and 80 MHz repetition rate. To our best knowledge, this spectrum bandwidth of NLP is the broadest among the reported YDF lasers. The autocorrelation function of pulse contained the short (30 fs) and long (4.6 ps) components. This short coherence light source is well suited for the optical coherent tomography used for ophthalmology at a wavelength of ∼1000 nm.

New loci and coding variants confer risk for age-related macular degeneration in East Asians.

Age-related macular degeneration (AMD) is a major cause of blindness, but presents differently in Europeans and Asians. Here, we perform a genome-wide and exome-wide association study on 2,119 patients with exudative AMD and 5,691 controls, with independent replication in 4,226 patients and 10,289 controls, all of East Asian descent, as part of The Genetics of AMD in Asians (GAMA) Consortium. We find a strong association between CETP Asp442Gly (rs2303790), an East Asian-specific mutation, and increased risk of AMD (odds ratio (OR)=1.70, P=5.60 × 10(-22)). The AMD risk allele (442Gly), known to protect from coronary heart disease, increases HDL cholesterol levels by 0.17 mmol l(-1) (P=5.82 × 10(-21)) in East Asians (n=7,102). We also identify three novel AMD loci: C6orf223 Ala231Ala (OR=0.78, P=6.19 × 10(-18)), SLC44A4 Asp47Val (OR=1.27, P=1.08 × 10(-11)) and FGD6 Gln257Arg (OR=0.87, P=2.85 × 10(-8)). Our findings suggest that some of the genetic loci conferring AMD susceptibility in East Asians are shared with Europeans, yet AMD in East Asians may also have a distinct genetic signature.

Three-dimensional optic nerve head images using optical coherence tomography with a broad bandwidth, femtosecond, and mode-locked laser.

PURPOSE: The aim of this study was to demonstrate the fine laminar structure of the optic nerve head (ONH), in vivo, using a broad wavelength, ultra-high resolution, and optically coherent tomography (OCT) system. METHODS: This high-resolution OCT system, based on a 200 nm bandwidth spectrometer and an 8 femtosecond ultra-short, mode-locked, coherent laser light source, enabled in vivo cross-sectional ONH imaging with 2.0 µm axial resolution. A total of 300 optic disc B-scans, which consisted of 300 × 2048 pixels, were obtained in 10 µm steps. Three-dimensional images were rendered from these images to obtain n face images of the optic disc. Fundus photography, scanning laser ophthalmoscopy (SLO), and standard OCT were also performed for all subjects. RESULTS: Thirty-six eyes of normal subjects and ten eyes of glaucoma patients with mean age of 40.0 ± 10.0 years were enrolled in this study. Sequential en face images, from the ONH surface to deeper layers, were reconstructed in 2.0 µm steps. Observation of the images indicated variations in the shape and arrangement of the lamina pores at different depths. Clear lamina pores were identified by this technique in 44 eyes, compared with the fundus camera (identified in six eyes), SLO (identified in 14 eyes), and standard OCT (identified in 24 eyes) (all comparisons, p < 0.001). CONCLUSIONS: The fine structure of the ONH could be resolved in vivo using our OCT, providing improved imaging that can be used in research and clinical applications for a better characterization of the anatomical and pathological features associated with glaucoma.

Prognostic phenotypic and genotypic factors associated with photodynamic therapy response in patients with age-related macular degeneration.

BACKGROUND: This study aimed to demonstrate the phenotypic and genotypic factors associated with photodynamic therapy (PDT) for age-related macular degeneration (AMD). METHODS: The study included 149 patients with exudative AMD treated by PDT. Eight phenotypic factors and ten genotypic factors for three single nucleotide polymorphisms (SNPs; rs800292, rs1061170, rs1410996) in the complement factor H (CFH) gene, rs 11200638-SNP in the high temperature requirement A-1 (HTRA1) gene, two SNPs (rs699947, rs2010963) in the vascular endothelial growth factor (VEGF) gene, and four SNPs (rs12948385, rs12150053, rs9913583, rs1136287) in the pigment epithelium-derived factor (PEDF) gene were evaluated. RESULTS: A significant association with best-corrected visual acuity change was demonstrated in the greatest linear dimension, presence or absence of pigment epithelial detachment, and HTRA1-rs11200638 genotype statistically (P=3.67×10(-4), 1.95×10(-2), 1.24×10(-3), respectively). Best-corrected visual acuity in patients with AA genotype of HTRA1-rs11200638 significantly decreased compared with that in patients with GG genotype (P=1.33×10(-3)). Logistic regression analyses demonstrated HTRA1-rs11200638 genotype was most strongly associated with best-corrected visual acuity outcome from baseline at 12 months after photodynamic therapy (P=4.60×10(-3); odds ratio 2.363; 95% confidence interval 1.303-4.285). CONCLUSION: The HTRA1-rs11200638 variant showed the most significant association. Therefore, this variant may be used as a prognostic factor to estimate the PDT response with significant predictive power.

A genome-wide association study for diabetic retinopathy in a Japanese population: potential association with a long intergenic non-coding RNA.

Elucidation of the genetic susceptibility factors for diabetic retinopathy (DR) is important to gain insight into the pathogenesis of DR, and may help to define genetic risk factors for this condition. In the present study, we conducted a three-stage genome-wide association study (GWAS) to identify DR susceptibility loci in Japanese patients, which comprised a total of 837 type 2 diabetes patients with DR (cases) and 1,149 without DR (controls). From the stage 1 genome-wide scan of 446 subjects (205 cases and 241 controls) on 614,216 SNPs, 249 SNPs were selected for the stage 2 replication in 623 subjects (335 cases and 288 controls). Eight SNPs were further followed up in a stage 3 study of 297 cases and 620 controls. The top signal from the present association analysis was rs9362054 in an intron of RP1-90L14.1 showing borderline genome-wide significance (Pmet = 1.4×10(-7), meta-analysis of stage 1 and stage 2, allele model). RP1-90L14.1 is a long intergenic non-coding RNA (lincRNA) adjacent to KIAA1009/QN1/CEP162 gene; CEP162 plays a critical role in ciliary transition zone formation before ciliogenesis. The present study raises the possibility that the dysregulation of ciliary-associated genes plays a role in susceptibility to DR.

Ocular localization and transduction by adenoviral vectors are serotype-dependent and can be modified by inclusion of RGD fiber modifications.

PURPOSE: To evaluate localization and transgene expression from adenoviral vector of serotypes 5, 35, and 28, ± an RGD motif in the fiber following intravitreal or subretinal administration. METHODS: Ocular transduction by adenoviral vector serotypes ± RGD was studied in the eyes of mice receiving an intravitreous or subretinal injection. Each serotype expressed a CMV-GFP expression cassette and histological sections of eyes were examined. Transgene expression levels were examined using luciferase (Luc) regulated by the CMV promoter. RESULTS: GFP localization studies revealed that serotypes 5 and 28 given intravitreously transduced corneal endothelial, trabecular, and iris cells. Intravitreous delivery of the unmodified Ad35 serotype transduced only trabecular meshwork cells, but, the modification of the RGD motif into the fiber of the Ad35 viral vector base expanded transduction to corneal endothelial and iris cells. Incorporation of the RGD motif into the fiber knob with deletion of RGD from the penton base did not affect the transduction ability of the Ad5 vector base. Subretinal studies showed that RGD in the Ad5 knob shifted transduction from RPE cells to photoreceptor cells. Using a CMV-Luc expression cassette, intravitreous delivery of all the tested vectors, such as Ad5-, Ad35- and Ad28- resulted in an initial rapid induction of luciferase activity that thereafter declined. Subretinal administration of vectors showed a marked difference in transgene activity. Ad35-Luc gene expression peaked at 7 days and remained elevated for 6 months. Ad28-Luc expression was high after 1 day and remained sustained for one month. CONCLUSIONS: Different adenoviral vector serotypes ± modifications transduce different cells within the eye. Transgene expression can be brief or extended and is serotype and delivery route dependent. Thus, adenoviral vectors provide a versatile platform for the delivery of therapeutic agents for ocular diseases.

Correlation between lamina cribrosa tilt angles, myopia and glaucoma using OCT with a wide bandwidth femtosecond mode-locked laser.

PURPOSE: To measure horizontal and vertical lamina cribrosa (LC) tilt angles and investigate associated factors using prototype optical coherence tomography (OCT) with a broad wavelength laser light source. DESIGN: Cross sectional study. METHODS: Twenty-eight no glaucoma eyes (from 15 subjects) and 25 glaucoma eyes (from 14 patients) were enrolled. A total of 300 optic nerve head B-scans were obtained in 10 µm steps and the inner edge of Bruch's membrane opening (BMO) was identified as the reference plane. The vertical and horizontal angles between BMO line and approximate the best-fitting line for the surface of the LC were measured and potential associated factors were estimated with univariate and multivariate logistic regression analyses. RESULTS: The median (interquartile range) horizontal and vertical tilt angles were 7.10 (2.43-11.45) degrees and 4.15 (2.60-6.85) degrees in eyes without glaucoma and 8.50 (4.40-14.10) degrees and 9.30 (6.90-14.15) degrees in glaucoma eyes, respectively. The refractive errors had a statistically significant association with horizontal LC tilt angles (coefficients, -1.53 per diopter) and glaucoma had a significant correlation with vertical tilt angles (coefficients, 6.56) using multiple logistic regression analysis (p<0.001). CONCLUSIONS: OCT allowed evaluation of the internal tilting of the LC compared with the BMO. The horizontal internal LC tilt angle was correlated with refractive errors, corresponding to myopic physiological changes, and vertical internal LC tilt was correlated with glaucoma, corresponding to glaucomatous pathological changes. These parameters have important implications for investigation of the correlation between myopia, glaucoma and LC morphological features.

[Corneal subepithelial infiltrates that developed following intravitreous injection of bevacizumab].

BACKGROUND: Anti-vascular endothelial growth factor (anti-VEGF) therapies including intravitrous bevacizumab injection (IVB) emerged as an effective treatment for various fundus diseases. Reports of adverse reactions derived from bevacizumab itself are rare. We report a case in which corneal subepithelial infiltrates developed following IVB. CASE: A sixty-six-year-old man presented with visual acuity loss due to cystic macular edema secondary to branch retinal vein occlusion. He developed vascular congestion and subepithelial infiltrates in the peripheral cornea on day 2 following the first IVB. The findings resolved with topical steroid in twelve days. CONCLUSION: A case of subepithelial infiltrate in the peripheral cornea following IVB is reported. Since infiltrates were located along, and associated with the congestion of, the limbal vascular arcade, an innate immune response to bevacizumab may be indicated.

Five-year results of photodynamic therapy with verteporfin for Japanese patients with neovascular age-related macular degeneration.

PURPOSE: To describe the treatment outcome of photodynamic therapy (PDT) in Japanese patients with age-related macular degeneration (AMD) followed for 5 years. PATIENTS AND METHODS: We retrospectively reviewed clinical charts of 51 patients with AMD. Thirty-one eyes of typical AMD (tAMD) and 20 eyes of polypoidal choroidal vasculopathy (PCV) were evaluated. RESULTS: The mean logarithm of the minimum angle of resolution (logMAR) vision of all AMD patients was 0.807 at the baseline examination and 0.937 at the 5 year examination. Mean visual acuity letter score loss is similar between patients with tAMD (-7.25) and with PCV (-5.36) at the month 60 examination. The patients with lesions of classic choroidal neovascularization (CNV) had 10.0 letters loss, but the patients with lesions of occult CNV had only 1.43 letters loss. The number of retreatments peaked in year 1 and declined immediately for patients with tAMD, but patients with PCV had significantly more frequent retreatments in the years 3 and 4 than patients with tAMD (P = 1.48 × 10(-2), 5.96 × 10(-3), respectively). CONCLUSION: Visual outcomes in patients with Japanese patients with AMD treated with PDT after 5-year follow up were worse than that in short-term follow up reported previously. In addition, the difference in visual prognosis between tAMD and PCV was not demonstrated after long-term follow-up.

Montage images of spectral-domain optical coherence tomography in eyes with idiopathic macular holes.

PURPOSE: To describe the morphologic and anatomic relationships at the vitreoretinal interface, from the macula into the periphery, in patients with idiopathic macular hole. Montaged images of posterior and peripheral spectral-domain (SD) optical coherence tomography (OCT) studies were used to describe the anatomic vitreoretinal relationships. DESIGN: Prospective, consecutive, observational case series. PARTICIPANTS: Forty-six eyes of thirty-six consecutive patients with idiopathic macular hole and their fellow eyes. METHODS: Montage images of 4 radial OCT scans (horizontal, vertical, and 2 oblique scans) through the fovea were obtained in each case. MAIN OUTCOME MEASURES: Montage SD OCT images. RESULTS: In fellow eyes, potential precursor changes to macular hole revealed shallow perifoveal vitreous separation that extends peripherally toward the equator. Two distinct configurations were noted at the posterior vitreous face; eyes without holes had a smooth curvature, whereas eyes with holes were more likely to have wavy, folded, or scalloped vitreous surfaces. At the onset of separation, most posterior vitreous cortex had a smooth curvature, but posterior vitreous folds increased with progressive separation. Also notable were zones of double-layered retinoschisis in regions of adherent posterior vitreous. Resulting granular hyperreflection in the peripheral vitreous was detectable in 50% to 60% of stage 1 or 2 holes but in only 33% of stage 3 or 4 holes. CONCLUSIONS: The SD OCT montages taken at serial stages of idiopathic macular holes document distinct configurations of the posterior vitreous face, granular hyperreflection in the peripheral vitreous, and areas of peripheral retinoschisis. Montaging SD OCT images provides novel cross-sectional images of the vitreoretinal interface that may have broader application. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Association of elastin gene polymorphism to age-related macular degeneration and polypoidal choroidal vasculopathy.

PURPOSE: To see if there is an association in Japanese between elastin gene (ELN) polymorphisms and neovascular age-related macular degeneration (AMD) or its subtypes, typical AMD (tAMD) and polypoidal choroidal vasculopathy (PCV). METHODS: The authors genotyped five single nucleotide polymorphisms (SNPs), rs2301995, rs2856728, rs868005, rs884843, and rs13239907, at Kyoto University and Saitama Medical University. A case-control study was performed on 1296 patients with AMD and 478 controls. RESULTS: A statistically significant association was detected between the rs2301995 SNP and AMD (P = 0.018). Furthermore, subtype analysis revealed a significant association of rs2301995 with tAMD (P = 0.0018), but not with PCV. The genotype distribution of rs2301995 also differed significantly between tAMD and PCV (P = 0.00030). The trend in genotype distribution of rs2301995 was similar between the Kyoto and the Saitama studies. The A allele frequency was higher in tAMD, whereas it was similar in PCV and in controls, which is opposite to that reported in a previous study that the A allele frequency is higher in PCV, whereas it is similar in tAMD and in controls. Haplotype analysis also showed that the ELN polymorphism is significantly associated with tAMD (P = 0.0055), but not with PCV. CONCLUSIONS: ELN is associated with AMD in Japanese. Furthermore, the findings suggest that ELN is a susceptibility gene for tAMD but not for PCV, which is opposite to that reported in a previous study that ELN is the susceptibility gene for PCV but not for tAMD.

Associations of cigarette smoking but not serum fatty acids with age-related macular degeneration in a Japanese population.

PURPOSE: To assess modifiable environmental risk factors and protective factors for age-related macular degeneration (AMD) in a native Japanese population. DESIGN: A case-control study. PARTICIPANTS: We included 422 case-control samples composed of 279 consecutive AMD cases and 143 controls. METHODS: Information regarding systemic conditions and lifestyle were documented in each subject by standardized questionnaire including age, gender, smoking history, body mass index (BMI), and history of cardiovascular disease, hypertension, and diabetes. Serum fatty acids profiles were analyzed by gas chromatography performed on blood samples taken from each study participant. Logistic regression and multiple comparison analyses were utilized in this study. MAIN OUTCOME MEASURES: Population-specific information assessing systemic conditions, lifestyle, and serum fatty acid profiles. RESULTS: Among environmental factors analyzed cigarette smoking showed the most significant association with development of all AMD (P<0.00001; odds ratio [OR], 4.06; 95% confidence interval [CI], 2.22-7.43), typical neovascular AMD (P<0.0001, OR, 4.59; 95% CI, 2.29-9.18), and polypoidal choroidal vasculopathy (P<0.001; OR, 4.87; 95% CI, 1.96-12.1). Hypertension and BMI showed a mild association with AMD. Although male prevalence was significantly higher in all case groups than in controls with conventional Scheffe correction, there was no association of gender with AMD development when logistic regression analysis was used to adjust for cigarette smoking. There was no difference in fatty acid profiles, except for a mild association of eicosapentaenoic acid concentration in the all AMD group. CONCLUSIONS: In the Japanese population studied, cigarette smoking influenced the risk of AMD but fractionated serum fatty acid levels did not. Although prior reports indicate a male predominance in Japanese patients with AMD, this study demonstrates that cigarette smoking accounts for this confounding bias. In addition, our population-specific data do not demonstrate significant differences in serum fatty acid composition, including ω-3 and ω-6 long chain polyunsaturated fatty acids, in Japanese patients with and without AMD. These results are consistent with the high proportion of smokers in aged Japanese men and the high fish oil intake in this population. FINANCIAL DISCLOSURE(S): The authors have no proprietary or commercial interest in any of the materials discussed in this article.

Complement factor H and high-temperature requirement A-1 genotypes and treatment response of age-related macular degeneration.

PURPOSE: To determine whether there is an association between complement factor H (CFH), high-temperature requirement A-1 (HTRA1), vascular endothelial growth factor (VEGF), and pigment epithelium-derived factor (PEDF) genotypes and response to treatment with photodynamic therapy (PDT) for age-related macular degeneration (AMD) in a Japanese population. DESIGN: Prospective, case-control study. PARTICIPANTS: One hundred ten patients with exudative AMD treated by verteporfin PDT were recruited prospectively at the Department of Ophthalmology, Saitama Medical University Hospital, Saitama, Japan. METHODS: The patients were genotyped for 4 single nucleotide polymorphisms (SNPs; rs800292, rs1061170, rs1410996, rs2274700) in the CFH gene, a rs11200638-SNP in the HTRA1 gene, 3 SNPs (rs699947, rs1570360, rs2010963) in the VEGF gene, and 4 SNPs (rs12150053, rs12948385, rs9913583, rs1136287) in the PEDF gene using a TaqMan assay. MAIN OUTCOME MEASURES: The treatment outcomes and genotypes of CFH, HTRA1, VEGF, and PEDF polymorphisms. RESULTS: Best-corrected visual acuity 1 year after PDT was significantly increased in patients with the HTRA1-rs11200638 GG genotype as compared with patients with the GA or AA genotypes (P = 2.9 × 10⁻², 7.0 × 10⁻4, respectively). The rate of recurrence in the 12-month period after PDT was also associated with HTRA1-rs11200638 genotype (P = 3.12 × 10⁻²). Patients with the AA genotype of HTRA1-rs11200638 had an approximately 6-fold greater risk of the recurrence than patients with the GG genotype (P = 5.58 × 10⁻³). Significant differences were demonstrated in the mean time interval from the initial treatment to the time of recurrence for the genotypes of CFH-rs1410996/-rs2274700 (P = 8.50 × 10⁻³). CONCLUSIONS: The HTRA1-rs11200638 and CFH-rs1410996/-rs2274700 variants were associated with response to PDT in this study population. These variants may be used for genetic biomarkers to estimate visual outcomes and recurrences in the response to PDT with significant predictive power.

[Outcome of photodynamic therapy for exudative age-related macular degeneration with good visual acuity].

PURPOSE: To evaluate visual outcome one year after photodynamic therapy (PDT) in patients with exudative age-related macular degeneration (AMD) showing good visual acuity (VA). SUBJECTS AND METHODS: One hundred and thirteen patients with AMD who received PDT therapy were recruited for this study. The study subjects were divided into two groups : those having a better visual acuity than 0.6 (n = 34), and those with VA worse than 0.5 (n = 79). All patients were examined by corrected visual acuity, fundus biomicroscopy, and optical coherence tomography (OCT) before, 1 month, 3 months, and 12 months after PDT. RESULTS: Visual acuity at 12 months was either at baseline visual acuity or improved in 82% of the better vision group. Foveal retinal thickness was significantly reduced with PDT in both the better vision and the worse vision groups (p = 0.04, 0.008, respectively). The greatest linear dimension (GLD) was significantly associated with significant vision decline among baseline factors (p = 0.049)such as gender and age. CONCLUSIONS: PDT is an effective adjunct for AMD patients even when they have good baseline vision. To perform PDT safely for AMD in patients with good vision, both larger GLD and retinal pigment epithelial detachment have to be considered as a risk factor.

Phenotype and genotype characteristics of age-related macular degeneration in a Japanese population.

PURPOSE: To describe phenotype and genotype characteristics of age-related macular degeneration (AMD) in Japanese patients. DESIGN: A case-control study. PARTICIPANTS: A total of 550 case-control samples composed of 408 consecutive AMD cases and 142 controls. METHODS: Clinical information assessing age, gender, affected eyes, fundus features, and fluorescein/indocyanine green angiograms were systematically evaluated. Four single nucleotide polymorphisms (SNPs; rs800292, rs1061170, rs1410996, rs2274700) in the complement factor H (CFH) gene, 1 SNP (rs11200638) in the high-temperature requirement factor A1 (HTRA1) gene, 3 SNPs (rs699947, rs1570360, rs2010963) in the vascular endothelial growth factor (VEGF) gene, and 4 SNPs (rs12150053, rs12948385, rs9913583, rs1136287) in the pigment epithelium-derived factor (PEDF) gene were assessed using TaqMan technology. MAIN OUTCOME MEASURES: The clinical phenotype information and genotypes of CFH, HTRA1, VEGF, and PEDF polymorphisms. RESULTS: Of Japanese patients with neovascular AMD (nAMD), 219 (58.7%) had typical nAMD and 154 (41.3%) had polypoidal choroidal vasculopathy (PCV). The frequency of bilateral exudative involvement was similar between typical nAMD (15.5%) and PCV (13.6%) (P = 0.613). Significant soft drusen were observed in the fellow eyes of 88 (47.6%) of 185 patients with unilateral typical nAMD and in 25 (18.8%) of 133 patients with unilateral PCV (P = 1.24x10(-7)). A serous pigment epithelium detachment was seen in 55 (25.1%) of 219 patients with typical nAMD and in 64 (41.6%) of 154 patients with PCV. A significant association was noted in CFH-rs800292, CFH-rs1410996, CFH-rs2274700, and HTRA1-rs11200638 with AMD development (P = 2.36x10(-5), 7.18x10(-5), 7.18x10(-5), 2.70x10(-7), respectively; population attributable risk = 57.3%, 57.8%, 57.8%, and 58.9%, respectively). We estimated the highest-risk group to have an approximately 70-fold greater risk of nAMD compared with the lowest-risk group when analyzing a combination of 4 SNPs in the CFH and HTRA1 genes. CONCLUSIONS: The Japanese AMD phenotype is characterized by a higher frequency of PCV, male predominance, and lower frequency of bilateral presentation compared with Caucasian AMD. Genotype analyses demonstrate a significant population attributable risk for SNPs in the CFH and HTRA1 genes and demonstrate joint effects for both genes. Gene variants in both CFH and HTRA1 contribute significantly to the AMD phenotype in a Japanese population.

Retinal adaptability loss in serous retinal detachment with central serous chorioretinopathy.

PURPOSE: To investigate the functional characteristics of the detached retina on a serous retinal detachment (SRD) in eyes with central serous chorioretinopathy (CSC) with spared visual acuity. METHODS: Multifocal electroretinograms (mfERGs) were recorded with a long recording time of 14 minutes, 34 seconds, to obtain accurate measurement of the second-order kernel (K2.1), an index of functional adaptability of the retina, from seven eyes with CSC (visual acuity, >or=1.0). The first-order kernel (K1) and the K2.1, elicited by stimulating the area of the SRD, were compared with those from the corresponding areas in eyes of 15 age-matched volunteers (controls) and in 6 eyes of patients with diabetic retinopathy (DR) that have been reported to have a K2.1 attenuation. RESULTS: K2.1 was essentially flat in the SRD eye. The K2.1 amplitude and log-scaled amplitude ratio of K2.1 to K1 (K2.1/K1) were severely reduced (to <95% confidence interval [CI] of control levels) in all eyes. The value of K2.1/K1 of the SRD was less than that in any of the control and DR eyes. K1 was moderately reduced but was not smaller than the 95% CI of control eyes. The mfERGs from the area without the SRD and those from the fellow eyes did not differ significantly from those in control eyes. CONCLUSIONS: A possible cause of the flat K2.1 observed on the SRD is the separation of the sensory retina. A substantial disparity between the recovery of cones and rods could contribute to the loss of retinal adaptability, resulting in the flat K2.1 as well as the unique visual impairments in CSC eyes.