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PurposeHuman leukocyte antigen (HLA) and immunity are related. Uveitis is also closely related to immunity. For example, the common presence of human leukocyte antigen (HLA)-DRB1*04 in the immune response is well known. The aim of this study was to investigate the relationship between visual prognosis and various HLA alleles before and after therapy in patients with unclassifiable uveitis, excluding those with Vogt-Koyanagi-Harada (VKH) disease.MethodsThis retrospective case series included 42 eyes from 22 consecutive patients with unclassifiable uveitis, excluding those with VKH disease. Visual acuity (VA), sex, refractive error, central retinal thickness (CRT), central choroidal thickness (CCT), and duration from onset to treatment were measured at initial and 6-month visits. Mean values of parameters were compared at each visit. Genotyping was performed by polymerase chain reaction amplification with sequence-specific primers.ResultsDRB1*04 showed a dominant change. No significant difference was observed in the other alleles. In DRB1*04, The mean differences in initial CCT, 6-month CCT, and 6-month VA showed statistically significant difference was found in best-corrected visual acuity (BCVA) between DRB1*04+ and DRB1*04− at the first visit. BCVA values at baseline and at the final visit were 0.13 ± 0.29 and 0.20 ± 0.36 in the DRB1*04+ and 0.00045 ± 0.20 and − 0.058 ± 0.11 in the DRB1*04− groups(p = 0.00465). Central Choroidal Thickness (CCT) values pretreatment and at the final visit after treatment were (pretreatment:361.00 ± 361.0 μm,after treatment: 286.00 ± 106.53 μm,p = 0.0174) in the DRB1*04+ group, and (pretreatment:281.3 ± 139.68 μm,after treatment:223.85 ± 99.034 μm,p = 0.0426) in the DRB1*04− group, respectively, indicating changes between baseline and the final visit. CCT was significantly greater in the DRB1*04+ group at both the initial visit and at 6 months. Multivariate analysis showed a significant difference between the presence or absence of DRB1*04 and sex.ConclusionHLA-DRB1*04 allele may affect visual prognosis and CCT in unclassifiable uveitis.

Tilted disc syndrome (TDS) may be associated with a macular serous retinal detachment (MSRD). However, ideal therapy for this complication is still unestablished yet to date. The purpose of this study is to investigate the effect of selective retina therapy (SRT) for MSRD associated with TDS. This retrospective study included 11 eyes of 10 patients (1 male and 9 females), who were treated with SRT for MSRD associated with TDS, and observed at least 12 months after treatment. The mean age was 56 years old (range 44–66). An SRT laser (527 nm, 1.7 μs, 100 Hz; Medical Laser Center Lubeck, Germany) was used for treatment. The changes of best-corrected visual acuity (BCVA), central macular thickness (CMT), and central choroidal thickness (CCT) were examined. Subfoveal curve height (SFCH) was calculated at baseline. The mean follow-up period was 24.4 months (range 12–48 months). The mean BCVA (logMAR), CMT, and CCT changed from 0.03 ± 0.10, 324 ± 82 μm, and 194 ± 68 μm preoperatively to 0.07 ± 0.17, 274 ± 94 μm, and 188 ± 65 μm at final follow-up, respectively, with significant difference on CMT (BCVA: p = 0.44, CMT: p < 0.05, CCT: p = 0.21). The MSRD disappeared in 6 eyes (55%) and the average number of SRT irradiations until resolution of MSRD was 2.6 times (range 1–5 times). There was no significant association between SFCH and resolution of MSRD (p = 0.19). SRT may promote absorption of MSRD and maintenance of BCVA for TDS. Randomized and prospective clinical studies are needed to evaluate the effectiveness of SRT for MSRD associated with TDS.

Purpose To describe the immunohistochemical profile in a case with focal nodular gliosis (FNG) of the retina. Methods A 56-year-old female patient presented with vitreoretinal tractional syndrome with FNG of the retina. After resection of the retinal tumor tissue during the 25-G pars plana vitrectomy, immunohistochemistry using anti-epidermal growth factor receptor (EGFR), p-53, Ki67, glial fibrillary acid protein (GFAP), CD34, and vascular endothelial growth factor antibodies was performed in the excised tissue of the FNG of the retina. Results Histopathological analysis of the tumor led to a diagnosis of FNG of the retina. Spindle cells of the tumor exhibited strong positive staining for glial fibrillary acid protein, and there was local staining for CD34 in the endothelial cells in the blood vessels. The epidermal growth factor receptor and vascular endothelial growth factor immunoreactivity were strongly observed in the endothelial cells. Conclusion This study demonstrated epidermal growth factor receptor expression in eyes with FNG of the retina. Oncogenic epidermal growth factor receptor might trigger and amplify the expression and function of endothelial vascular endothelial growth factor.

The purpose of this study was to investigate the occurrence rate and predictors of photodynamic therapy (PDT) induced acute exudative maculopathy (PAEM). This retrospective study included 39 eyes of 39 patients (32 males and 7 females), who were treated with initial PDT. PAEM was defined as an increase in central retinal thickness (CRT) of 10% or more measured by OCT on day 3 after PDT compared with baseline. Sixteen of 39 eyes (41%) were classified in the PAEM+ group. CRT and central choroidal thickness (CCT) were significantly increased at 3 days in the PAEM+ group and significantly decreased at 1 month after PDT in the PAEM- group. In a multiple comparison, neovascular age-related macular degeneration (nAMD) had a significantly higher incidence of PAEM compared to polypoidal choroidal vasculopathy (PCV) and central serous chorioretinopathy (CSC). The incidence of PAEM was lower in PCV and CSC, and higher in nAMD. BCVA at 1 month was significantly worse in the PAEM group, which may be related to visual prognosis after PDT. Since both CRT and CCT decrease at 1 month, the detection of PAEM needs to be assessed a few days after PDT.

To identify susceptibility genes for macular neovascularization (MNV) development in central serous chorioretinopathy (CSC).Genome-wide survival analysis using a longitudinal cohort study.We included 402 and 137 patients with CSC but without MNV at their first visit from the Kyoto CSC Cohort and Kobe CSC dataset, respectively. All patients underwent detailed ophthalmic examinations, including multimodal imaging, such as fundus autofluorescence, spectral-domain OCT, and fluorescein angiography/indocyanine green angiography or OCT angiography.We conducted a genome-wide survival analysis using the Kyoto CSC Cohort. We applied the Cox proportional hazard model to adjust for age, sex, and the first principal component. Single nucleotide polymorphisms (SNPs) with P values1.0 × 10The association between SNPs and MNV development in patients with CSC.Rs370974631 near ARMS2 displayed a genome-wide significant association in the meta-analysis of discovery and replication result (hazard ratio [HR]ARMS2, CFH, COL4A3, and B3GALTL were identified as susceptibility genes for MNV development in CSC. These 4 genes are known as susceptibility genes for AMD, whereas COL4A3 and B3GALTL were previously reported to be polypoidal choroidal vasculopathy (PCV)-specific susceptibility genes. Our findings revealed the shared genetic susceptibility between PCV and MNV secondary to CSC.

Background The common presence of human leukocyte antigen (HLA)-DRB1*04 in Vogt-Koyanagi-Harada (VKH) disease is well known. The aim of this study was to investigate the relationship between visual prognosis and HLA-DRB1*04 alleles during systemic corticosteroid therapy in patients with VKH disease. Methods This retrospective case series included 57 eyes from 29 consecutive patients with treatment-naïve VKH disease who received systemic corticosteroid therapy. Visual acuity, sex, refractive error, central retinal thickness (CRT), central choroidal thickness (CCT), and duration from onset to treatment were measured at initial and final visits. Mean values of parameters were compared with each visit. Genotyping was performed by polymerase chain reaction amplification with sequence-specific primer. Results Linear regression showed significant differences in logMAR best-corrected visual acuity between the three groups of homozygotes, heterozygotes, and normal subjects at baseline (p p p = 0.257). No significant differences were detected between the three groups in age, sex, refractive error, CRT, CCT, or duration from onset to treatment. Conclusion Alleles of HLA-DRB1*04 might affect visual prognosis and be related to early response after initiation of treatment in VKH disease.

To determine the association of age-related maculopathy susceptibility 2 (ARMS2) gene polymorphisms with the 12-month outcomes of intravitreal aflibercept combined with photodynamic therapy (IVA+PDT) in polypoidal choroidal vasculopathy (PCV). Interventional cohort study. This was a retrospective study of 48 consecutive treatment-naive PCV patients. The patients underwent IVA+PDT as the initial therapy and were followed up for more than 12 months under a pro re nata regimen. The single nucleotide polymorphism (SNP) at rs10490924 in the ARMS2 gene was genotyped using the TaqMan assay. The clinical characteristics and outcomes of IVA+PDT were compared among the 3 genotypes at rs10490924. Multivariate regression analysis was performed to evaluate the influence of the clinical cofactors on the association of rs10490924 with the visual outcome at 12 months after the first IVA+PDT. No significant difference was found in the baseline characteristics among the 3 genotypes (n = 9, 23, and 16 for the GG, GT, and TT genotypes, respectively). All the patients, regardless of genotype, showed a significant improvement in vision, central retinal thickness, and subfoveal choroidal thickness at all time points measured after the initial IVA+PDT. The number of treatments was significantly smaller in the patients with the GG genotype than in those with the GT or the TT genotype. On multivariate logistic regression analysis, the number of the T allele at rs10490924 was significantly associated with the chance of retreatment after the initial IVA+PDT. The presence of the G allele at rs10490924 in the ARMS2 gene is likely associated with a lower chance of retreatment after IVA+PDT in patients with PCV.

Background Diagnostic vitrectomy is an important method for evaluating uveitis, and its diagnostic utility is high regardless of whether the uveitis is infectious or non-infectious. The course of diagnostic vitreous surgery with 27-gauge pars plana vitrectomy and perioperative complications is reported. Methods An observational retrospective study of patients who underwent 27-gauge diagnostic vitrectomy due to atypical intraocular inflammation was conducted. The final diagnosis rate, complications due to surgery, preoperative visual acuity, and postoperative visual acuity (1 month and 6 months after surgery) were examined retrospectively. Results Diagnostic vitreous surgery was performed in 32 patients and 35 eyes (14 males and 18 females, age 14–85 years, median 67 years) during the study period. The average operation time was 52 min for 19 eyes with cataract surgery and 35 min for 16 eyes without cataract surgery. Preoperative log(minimum angle of resolution [MAR]) visual acuity was 0.84 ± 0.87, 1-month postoperative logMAR visual acuity was 0.41 ± 0.55 (p = 0.004, n = 28), and 6-month postoperative average logMAR visual acuity was 0.45 ± 0.73 (p = 0.012, n = 15). The diagnosis was made by diagnostic vitrectomy in 19 cases (54%). Postoperative complications were observed in 2 of 35 postoperative patients (5%); one involved increased intraocular pressure, and the other case involved vitreous hemorrhage of the eye, necessitating reoperation. Conclusion Diagnostic 27-gauge vitrectomy could be effective for evaluating intraocular inflammation.

Purpose: To describe two cases of extremely high-IL-6 pan-uveitis with subretinal exudation and cell migration.Methods: Pre-operative and postoperative images and IL-6 values in vitreous samples of two pan-uveitis cases were analyzed.Results: Case 1 was a 76-year-old man with blurry vision in his right eye. Fundus examination and optical coherence tomography showed vitreous opacification with vitreous cells and the presence of a white-yellowish retinal exudate with peripheral choroidal detachment all around. The IL-6 value was 16,600 pg/ml. Case 2 was a 63-year-old man with blurry vision in his right eye. On fundus examination, there was severe vitreous opacification in his right eye. The IL-6 value was 26,600 pg/ml. Importantly, there was good responsiveness to steroids and the TNF inhibitor.Conclusion: Unclassified intraocular inflammation might include a new category of disease with unilateral pan-uveitis with good response to steroid therapy and extremely high vitreous IL-6 values.

Purpose To report a case of a patient with subretinal fluid (SRF) associated with choroidal nevus (CN), who was treated with selective retina therapy (SRT) and ultimately achieved resolution of the SRF. Observations A 41-year-old man with SRF associated with CN in his right eye (RE) underwent ophthalmologic evaluation, including optic coherence tomography, fluorescein angiography (FA) and indocyanine green angiography. The best corrected visual acuity (BCVA) converted to the logarithm of the minimum angle of resolution (logMAR) was 0.00 in the RE. SRT (532 nm, 1.7 μs pulse duration, 30 pulses in 100Hz; Medical Laser Center Lubeck) was performed with the laser spots equally distributed across the FA leakage area. Until 20 months SRT was repeated several times because the SRF decreased every time in response to SRT, but was not completely resolved and sometimes increased with time. After performing 6 times of SRT session, leakage on FA stopped at 21 months follow-up and SRF was resolved at 31 months. At 60 months after the first SRT, there were no signs of malignant transformation, no SRF, and the BCVA in the RE was 0.22. Conclusions and Importance SRT seems to be a useful treatment and proper clinical studies are necessary to establish the best treatment protocol for SRF associated with CN.

Background To investigate preoperative clinical factors and visual outcomes of Japanese patients with dysthyroid optic neuropathy (DON) after urgent orbital decompression. Methods This retrospective, observational case series study investigated 44 patients who exhibited several preoperative clinical factors that might be associated with the need for urgent orbital decompression due to DON. Additionally, the visual acuity of DON patients was compared between the patients preoperatively and at 1 and 6 months postoperatively. Results All 44 patients received steroid and with or without radiation therapy, with 27 patients able to avoid undergoing urgent surgery. However, the remaining 17 patients required urgent orbital decompression following a lack of response to the therapy. None of the patients who initially avoided surgery required additional surgery for DON. Factors significantly associated with the need for urgent orbital decompression surgery included: female gender, older age, long disease duration, unilateral significant DON, history of resistance to pulsed steroid therapy, unstable thyroid function, high TRAb (Thyrotrophin receptor antibody)value, poor visual acuity, presence of central diplopia, and presence of corneal problems (P Conclusion This study revealed several preoperative clinical factors for DON that appear to be associated with the need for urgent orbital decompression surgery in Japanese patients.

This study was prospectively carried out to clarify the effectiveness of visual and anatomical outcomes under combination therapy of intravitreal aflibercept (IVA) and verteporfin photodynamic therapy (vPDT) in over 24 months. A single-arm prospective exploratory study. Twenty-six eyes of 26 treatment naive PCV patients were enrolled in this study. The primary outcome measures were the changes in best corrected visual acuity (BCVA) and the complete polyp regression rate. The secondary outcome measures included central retinal thickness assessed by optical coherence tomography. The patients showed significant improvement in BCVA by 0.14 logMAR units at 12 months and 0.11 logMAR units at 24 months from baseline (both p

Purpose: This study evaluates optical coherence tomography (OCT) findings of the macula in patients with a history of retinopathy of prematurity (ROP). Methods: We enrolled 112 patients (age: 6–15 years) and categorized them into 3 groups: gestational age (GA) < 36 weeks with or without a history of ROP (ROP group, preterm group) and GA ≥37 weeks. We included 1 eye of each patient and measured the retinal thickness of the macula by OCT. Results: The ROP group demonstrated the worst VA and the shallowest foveal depression. Furthermore, foveal depression significantly correlated with birth weight, GA, ganglion cell layer/inner plexiform layer (GCL-IPL) thickness, and a history of ROP. Conclusions: This study established a correlation of fovea formation with premature birth, damage of GCL-IPL, and a history of ROP. The retention of the inner retina possibly contributes to abnormal foveal morphology in patients with a history of ROP.

Purpose: To report a case of polypoidal choroidal vasculopathy associated with optic disc coloboma. Methods: Case report. Results: A 50-year-old woman presented with optic disc coloboma and retinochoroidal coloboma associated with subretinal hemorrhage and serous retinal detachment (SRD) in her left eye. Optical coherence tomography (OCT) confirmed SRD at the macula and showed a sharply elevated retinal epithelial detachment at the choroidal excavation. OCT also revealed choroidal cavitation along the temporal side of the optic coloboma. Fluorescein angiography showed hyperfluorescent dye leakage and indocyanine green angiography revealed polypoidal lesions. We diagnosed polypoidal choroidal vasculopathy (PCV). PCV was located at the end of the choroidal cavitation. Her left eye was treated with an intraocular injection of the anti-vascular endothelial growth factor aflibercept (2 mg). Photodynamic therapy was performed using the standard protocol 1 week after the intravitreal application of aflibercept. One month after the combined treatment, OCT showed completely resolved SRD and her symptoms disappeared. Her best-corrected visual acuity remained stable and no recurrence was found during a 12-month follow-up period. Conclusion: PCV associated with optic disc coloboma has not been previously reported. The morphological abnormality of choroidal cavitation and choroidal excavation connecting with optic disc coloboma may contribute to the development of PCV in this case.

Central serous chorioretinopathy (CSC) is a common choroidal disorder which often affects the vision of young adults. Although the molecular mechanisms associated with CSC remain unknown, correlations between steroid hormone use and CSC have been suspected. We investigated the choroidal status of CSC secondary to corticosteroid use.The records of 25 eyes of 25 consecutive acute CSC cases secondary to corticosteroid use were reviewed retrospectively. Central choroidal thickness was measured by optical coherent tomography. Choroidal vessel dilation and choroidal vascular hyperpermeability were evaluated based on indocyanine green angiography findings. The parameters related to secondary CSC were compared with those of 25 eyes of 25 cases with acute idiopathic CSC.The mean central choroidal thickness of secondary CSC was 294.8 ± 95.0 μm, which was significantly thinner than that of idiopathic CSC (409.4 ± 124.7 μm, P = 0.00064). The proportion of the cases exhibiting choroidal vessel dilation was not significantly different between secondary CSC (52%) and idiopathic CSC (64%). The proportion of cases showing choroidal vascular hyperpermeability was significantly smaller in secondary CSC (62%) than idiopathic CSC (92%) (P = 0.028).The choroidal status in the acute phase of secondary CSC after corticosteroid use might be different from that of idiopathic CSC, which suggests a complex mechanism for CSC.

Abstract Background: The common presence of human leukocyte antigen (HLA)-DRB1*04 in Vogt-Koyanagi-Harada (VKH) disease is well known. The aim of this study was to investigate the relationship between visual prognosis and HLA-DRB1*04 alleles during systemic corticosteroid therapy in patients with VKH disease. Methods: This retrospective case series included 57 eyes from 29 consecutive patients with treatment-naïve VKH disease who received systemic corticosteroid therapy. Visual acuity, sex, refractive error, central retinal thickness (CRT), central choroidal thickness (CCT), and duration from onset to treatment were measured at initial and final visits. Mean values of parameters were compared with each visit. Genotyping was performed by polymerase chain reaction amplification with sequence-specific primer. Results: Linear regression showed significant differences in logMAR best-corrected visual acuity between the three groups of homozygotes, heterozygotes, and normal subjects at baseline ( p

To investigate the predictive factors of clinical outcome of selective retina therapy (SRT) for diabetic macular edema (DME). This retrospective study included 22 eyes of 22 patients (15 males and 7 females), who were treated with SRT for DME at the Department of Ophthalmology of Osaka City University Hospital and observed at least 6 months after the treatment. The mean age was 64 years (range 40–81). Thirteen of the 22 eyes (59%) had a treatment history other than SRT before. SRT laser (527 nm, 1.7 µs, 100 Hz) was used for treatment. Changes in the best-corrected visual acuity (BCVA) (logMAR) and central macular thickness (CMT) in optical coherence tomography were examined at baseline, 3-month follow-up, and 6-month follow-up. Factors associated with the rate of change in CMT at 3 and 6 months after SRT were examined. The mean BCVA (logMAR) was 0.26 ± 0.31, 0.22 ± 0.27 and 0.23 ± 0.29 at baseline, 3 months and 6 months, respectively (p = 0.15 at 3 months, 0.40 at 6 months; compared to baseline). The mean CMT was 502 ± 163, 493 ± 204, and 416 ± 185 μm at baseline, 3 months, and 6 months, respectively (p = 0.69 at 3 months, 0.01 at 6 months; compared to baseline). The multivariate analysis found a significant negative association with previous macular photocoagulation (p = 0.03) at 3 months and a positive association with a history of insulin use (p = 0.02) and previous panretinal photocoagulation (p = 0.03) at 6 months after SRT. The CMT was significantly decreased at 6 months after SRT in DME. The history of insulin use and panretinal photocoagulation may positively and the history of macular photocoagulation may negatively affect the outcome of SRT, which must be considered when determining the therapeutic indications for SRT.

The purpose of the study was to evaluate the 1-year visual and anatomical outcomes of combination therapy with intravitreal aflibercept (IVA) and verteporfin photodynamic therapy (vPDT) for polypoidal choroidal vasculopathy (PCV), and to determine the predictors of a good visual outcome. This was a prospective case-series study. Twenty eyes from 20 treatment-naive PCV patients were treated with combination therapy with IVA and vPDT. Best-corrected visual acuity (BCVA) and morphological parameters including polypoidal lesions in indocyanine green angiography (ICGA) were evaluated over 12 months of follow-up. The mean logMAR BCVA was significantly improved from 0.30 at baseline to 0.20 at 3 months and 0.18 at 12 months. The mean central retinal thickness was also significantly improved at 3 months and at 12 months. In ICGA, complete regression of polypoidal lesions was found in 14 out of 20 eyes (70 %) at 3 months and in 14 out of 18 eyes (78 %) at 12 months although no ICGA were done on two eyes. In the multivariate logistic regression analyses, the baseline greatest linear dimension was found as a significant predictive factor for good visual improvement (≧0.3 LogMAR units improvement from baseline) at 12 months. In this study, combination therapy with IVA and vPDT gave visual and anatomical improvements to treatment-naive PCV patients over 12 months of follow-up period.

Background and objectives This study aimed to compare the efficacy of fluorescein angiography (FA)-guided and indocyanine green angiography (ICGA)-guided half-time photodynamic therapy (PDT) for central serous chorioretinopathy (CSC). Subjects and methods Medical records of 61 eyes of 61 CSC patients who underwent half-time PDT were retrospectively reviewed. The irradiation area was determined using information from FA or ICGA with physicians’ discretion. Best-corrected visual acuity (BCVA), central retinal thickness (CRT), subfoveal choroidal thickness (SCT), and resolution of subretinal fluid (SRF) were evaluated at baseline and 1, 3, 6, and 12 months after PDT. Results A total of 29 and 32 eyes received FA-guided PDT (irradiation area, 2898.3 ± 705.7 μm) and ICGA-guided PDT (irradiation area, 4993.8 ± 333.1 μm), respectively. A significant improvement in the mean BCVA was found at 1 month in the FA-guided group (P = 0.02), but not in the ICGA-guided group (P = 0.88). BCVA was significantly improved in both groups at 3, 6, and 12 months with no significant intergroup difference at any time points. CRT and SCT were significantly reduced in both groups at all time points with no significant intergroup differences. No significant intergroup differences were observed in the rate of recurrence and persistent SRF. However, there was a significant difference between groups in the rate of recurrence and/or persistent SRF (P = 0.04). Multivariate analysis revealed that choice of FA-guided was significantly associated with recurrence and/or persistent SRF (P = 0.04). Conclusion Half-time PDT with ICGA-guided irradiation spot might be more effective than that with FA-guided in treating CSC patients in complete resolution of SRF.

To investigate the clinical characteristics of eyes with cuticular drusen in Japanese individuals, while paying special attention to large colloid drusen (LCD). Retrospective case series. Eyes with cuticular drusen, from patients of 4 medical institutes in Japan, were investigated. Multimodal imaging findings were used to diagnose cuticular drusen. LCD was defined as cuticular drusen > 200 µm. Twenty-four eyes from 12 patients (8 women, 4 men) were diagnosed with cuticular drusen. The mean age of all patients (n = 12) was 60.8 years. The mean age of patients without additional macular pathology (n = 5) was 55.4 years. Of the 7 patients with additional macular pathology, 6 (85.7%) exhibited age-related macular degeneration-associated macular pathology, including drusenoid pigment epithelial detachment (PED) (8 eyes from 4 patients), geographic atrophy (2 eyes from 1 patient), and occult choroidal neovascularization (1 eye). LCD were found in 6 eyes of 3 patients (25%), those with LCD were on average 53.7 ± 8.7 years old and those without 69.9 ± 14.1 years of age (P = 0.064, Mann–Whitney U test). Cuticular drusen were predominantly seen in females, and drusenoid PED was most frequently seen in eyes with additional macular pathology. LCD were seen in 25% of eyes with cuticular drusen.

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 −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.

Miki Hirose, Wataru Matsumiya, Shigeru Honda, Makoto NakamuraDepartment of Surgery, Division of Ophthalmology, Kobe University Graduate School of Medicine, Chuo-ku, Kobe, Hyogo, JapanPurpose: Our aim was to investigate the efficacy and prognostic factors of intraocular injections of bevacizumab as needed in patients with macular edema secondary to central retinal vein occlusion (CRVO).Methods: This is a retrospective study including 28 eyes of 27 consecutive patients with macular edema due to CRVO and followed for at least 6months. The mean age of the patients was 66.3years. The patients underwent an intravitreal injection of bevacizumab (1.25mg) at the initial visit. Retreatments were performed when macular edema was persistent or worsened (as-needed regimen). The primary outcome measure was the mean change in best-corrected visual acuity (BCVA). The change in central retinal thickness (CRT) was evaluated as the secondary outcome. Finally, the factors useful for predicting BCVA outcome were determined.Results: The mean number of injections was 1.8 over a period of 6months. The mean BCVA (logarithm of minimum angle of resolution) was significantly improved at 1 (-0.097), 3 (-0.14), and 6 months (-0.25) after the initial injection (P

Background: To compare the outcomes of photodynamic therapy (PDT) between two different angiographic subtypes of polypoidal choroidal vasculopathy (PCV). Methods: Ninety-three consecutive cases of PCV were classified into two phenotypes (42 type 1 and 51 type 2) according to the presence or absence of feeding vessels found on indocyanine green angiography. Full-dose PDT and retreatments were performed every 3 months as needed based on the findings on angiography. The best-corrected visual acuity (BCVA) was compared as the main outcome between type 1 and type 2 PCV up to 12 months after the initial PDT. Results: The baseline greatest linear dimension (GLD) was significantly larger in type 1 PCV than type 2 PCV. The mean BCVA was significantly improved from baseline in type 2 PCV, while no improvement was found in type 1 PCV. Analysis with matching the GLD between both PCV subtypes did not change the original results. Conclusions: There may be a significantly different response to PDT between two angiographic phenotypes of PCV.

Aim: To report a case of choroidal neovascularization secondary to unilateral retinal pigment epithelium dysgenesis (URPED), which was resistant to posterior subtenon injection of triamcinolone acetonide (STTA) and intravitreal bevacizumab injection (IVB). Case Report: An 8-year-old boy was referred to us because of a unilateral unique clinical appearance on funduscopic examination in his left eye (OS). A geometric lesion at the retinal pigment epithelium level of the interpapillomacular area was disclosed OS. The optic nerve was slightly hyperemic OS. Findings from the right fundus examination were normal. Based on these characteristic findings, he was diagnosed as having URPED. Best corrected Landolt ring chart visual acuity (BCVA) was 1.0 in both eyes. Twenty-three months after the first visit, the patient presented with visual disturbance OS. Funduscopic examination showed an expansion of the geometric lesion and the development of a subfoveal choroidal neovascularization (CNV). BCVA was 0.4 OS. Two-time STTA (40 mg/1 ml) was performed at the onset of CNV and 6 months later, and additional IVB (1.25 mg/0.05 ml) was done 10 months later for the treatment of CNV, but the geometric lesion and CNV were resistant to the treatment and continued to expand. Seven years after the first visit, the geometric lesion and the CNV kept expanding steadily. Conclusion: URPED is a rare clinical entity, and the prognosis of this disease is still unclear. The visual prognosis may depend on whether CNV fully develops.

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.

Background Choroidal neovascularisation is often associated with pathological myopia. Bisphosphonates (BP), the preferred drug for treatment of osteoporosis, are known to have anti-angiogenic effects. Objective To compare the therapeutic effects of oral BP with anti-vascular endothelial growth factor therapy (anti-VEGF) and photodynamic therapy (PDT) for myopic choroidal neovascularisation (mCNV) over 2 years of follow-up. Methods One hundred eyes of 96 consecutive patients with mCNV who underwent oral BP treatment (alendronate 5 mg/day or 35 mg/week), anti-VEGF therapy, PDT or observation only were followed up for 2 years. The best-corrected visual acuity (BCVA) and the central retinal thickness (CRT) in optical coherence tomography were compared among the treatment groups. Results The mean BCVA of the patients was maintained for up to 2 years in the BP and PDT groups. In the anti-VEGF group, the mean BCVA was significantly improved but was significantly worse in the no-treatment group. The visual outcomes were significantly better in the BP, PDT and anti-VEGF groups than the no-treatment group over 2 years of follow-up (−0.28, −0.26 and −0.39 logMAR units, p=0.032, 0.021 and 0.0004, respectively). The mean CRT was significantly decreased in all treatment groups (−84, −121 and −122 mm, p=0.0025, 0.017 and 0.000025, respectively). Conclusions Oral BP should be investigated further as possible therapeutic and preventive drugs for mCNV.

To evaluate the long-term effects of photodynamic therapy (PDT) on typical neovascular age-related macular degeneration (tAMD) and polypoidal choroidal vasculopathy (PCV). This was a multicenter prospective study of 139 eyes from 136 patients (tAMD: 74 eyes; PCV: 65 eyes) who underwent PDT as the initial treatment. The change in best-corrected visual acuity (BCVA), predictive factors for the BCVA at 60 months, frequency of recurrence, and mean recurrence period were analyzed. The pre-PDT BCVA and greatest linear dimension (GLD) did not differ between the two groups. The mean BCVA (logMAR) was significantly improved at 6 months post-initial PDT (post-PDT) in the PCV group (−0.11, P = 0.0091). However, at 60 months post-PDT, the mean BCVA was significantly worse than baseline in the tAMD (+0.21, P = 0.0035) and PCV (+0.21, P = 0.0076) groups. Pre-PDT BCVA, age, and GLD were the factors significantly associated with the BCVA at 60 months post-PDT. Although the frequency of recurrence did not significantly differ between the two phenotype groups, the mean recurrence period was significantly longer in the PCV group than in the tAMD group (15.7 vs. 8.6 months, P = 0.0020). PDT may not have benefits for visual acuity in cases of tAMD and PCV over 5 years of follow-up.

To compare the association of age-related maculopathy susceptibility 2 (ARMS2) and complement factor H (CFH) variants between two different angiographic phenotypes of polypoidal choroidal vasculopathy (PCV).We included 175 Japanese patients with PCV and 150 age- and sex-matched controls. PCV was classified into two phenotypes (Type 1 and Type 2) according to the presence or absence of the feeding vessels found in indocyanine-green angiography. The single nucleotide polymorphism (SNP) at rs10490924 (A69S) in ARMS2 and rs800292 (I62V), rs1061170 (Y402H) in the CFH region were genotyped using the TaqMan assay.The minor allele frequency (MAF) of rs10490924 was significantly different between Type 1 PCV (n = 81) and control (p0.0001), while no difference was found between Type 2 PCV (n = 94) and control (p = 0.20). The MAF of rs800292 was significantly different between each type of PCV and control (p0.0001 and 0.0001 for Type 1 versus control and Type 2 versus control, respectively). The MAF of rs1061170 was not significantly different between either type of PCV and control (p = 0.084 and 0.15, respectively).There may be significantly different associations in the genetic variants of ARMS2 between two angiographic phenotypes of PCV.

Age-related macular degeneration (AMD) is a major cause of blindness in the elderly. Previous sequencing studies of AMD susceptibility genes have revealed the association of rare coding variants in CFH, CFI, C3 and C9 in European population; however, the impact of rare or low-frequency coding variants on AMD susceptibility in other populations is largely unknown. To identify the role of low-frequency coding variants on exudative AMD susceptibility in a Japanese population, we analysed the association of coding variants of 34 AMD candidate genes in the two-stage design by a multiplex PCR-based target sequencing method. We used a total of 2,886 (1st: 827, 2nd: 2,059) exudative AMD cases including typical AMD, polypoidal choroidal vasculopathy, and retinal angiomatous proliferation and 9,337 (1st: 3,247 2nd: 6,090) controls. Gene-based analysis found a significant association of low-frequency variants (minor allele frequency (MAF)

Purpose: To report a case who had recurrence of macular hole retinal detachment (MHRD) after intravitreal ranibizumab injection (IVR) for the treatment of choroidal neovascularization (CNV) that arose from the damaged retinal pigment epithelium of the remaining macular hole (MH) edge, which had been successfully treated by pars plana vitrectomy (PPV) 15 years previously. Case Report: A 67-year-old man with previous PPV for MHRD secondary to high myopia in the right eye had been under observation for 15 years after surgery. The retina had been successfully attached, but the MH remained open. He had CNV which arose from the remaining MH edge. IVR was performed for the treatment of CNV. One month after the injection, CNV was contracted but recurrence of MHRD occurred. PPV with an additional internal limiting membrane peeling, removal of the CNV membrane and 20% SF6 gas tamponade was performed. One year after the last surgery, his right retina was attached and the MH was closed successfully. Conclusion: We propose that patients who undergo IVR should be carefully maintained and followed up for possible complications including the recurrence of MHRD.

Purpose: To report a case of proliferative diabetic retinopathy (PDR) showing transient macular edema (ME) and deteriorated retinal function after intravitreal bevacizumab injection (IVB). Methods and Results: A 53-year-old man received IVB (1.25 mg/0.05 ml) in both eyes for the treatment of PDR. There was no treatment-related complication. However, he complained of photopsia in both eyes 6 h after the injection. Slit-lamp examination revealed mild cellular infiltrations (1+) in the anterior chamber in both eyes. Optical coherence tomography showed ME formation in the left eye. Both full-field and multifocal electroretinography (ERG) revealed the deterioration of all parameters in both eyes compared with pretreatment. The inflammation in the anterior segment and ME disappeared 1 day after the injection. ERG parameters were improved 9 days after the injection, except for the N1 and P1 amplitude of multifocal ERG in the left eye. Conclusion: We propose that patients who undergo IVB should be carefully informed and followed up for possible complications including temporal ME formation and retinal function deterioration.

Purpose: To evaluate the retinal toxicity of intravitreal tissue plasminogen activator (tPA) injection for branch and central retinal vein occlusion (BRVO and CRVO) using the electroretinogram (ERG). Procedures: Ten BRVO patients and 5 CRVO patients were enrolled. A complete examination including full-field ERG, visual acuity, central retinal thickness (CRT), and evaluation of systemic and ocular complications was performed before and after intravitreal tPA injection. Results: No significant differences were found in the amplitude or implicit time of any ERG component after tPA injection, and no systemic or ocular complication was observed. The improvement of visual acuity was significant at month 3 in the BRVO group (p < 0.05) but not in the CRVO group. CRT significantly decreased over the course of 3 months in both groups (p < 0.01). Conclusion: Intravitreal tPA injection seems to be a safe and effective treatment option for macular oedema caused by retinal vein occlusions.

To evaluate the anti-angiogenic effects of integrin alphavbeta3 specific antagonist BS-1417 on laser-induced choroidal neovascularization (CNV) in mice.Male C57BL/6 mice were treated with daily intraperitoneal injections of BS-1417 or saline starting at the onset (day 0) of experiments. CNV was induced by laser photocoagulation the next day. Fluorescein angiograms (FA) and choroidal flatmount FITC-dextran perfusion were performed on experimental day 8. Histological and immunohistochemical examinations were performed with consecutive cryosections. Sub-confluent human vascular endothelial cells (HUVEC) were grown in vitro under various concentrations (0-10 microg/ml) of BS-1417 and the numbers of cell were measured at 48 hours of incubation. After fixation, immunocytochemistry was performed.BS-1417 significantly decreased the area of dye leakage determined by FA (40% of control, p = 0.0008) and reduced the CNV size found on choroidal flatmount (18% of control, p = 0.007). In histological findings, BS-1417 apparently suppressed the size of laser-induced CNV. Immunoreactivities for VEGF and integrin alphav were remarkably attenuated with BS-1417 compared to control. BS-1417 inhibited the growth and VEGF expression of HUVEC in vitro.The integrin alphavbeta3 may play a key role in the induction of laser-induced CNV. The antagonists for integrin alphavbeta3 may have therapeutic effects in CNV associated diseases such as age-related macular degenerations.

To evaluate the safety and efficacy of intravitreal injection of bevacizumab advanced to vitrectomy for severe proliferative diabetic retinopathy. Eight eyes of six patients (33–64 years old, all male patients) with severe proliferative diabetic retinopathy were investigated. An intravitreal injection of 1.25 mg bevacizumab was performed 3–30 days prior to planned vitrectomy. All cases showed minimum bleeding during surgical dissection of fibrovascular membrane. Two cases receiving bevacizumab 7 days before the surgery showed strong fibrosis and adhesion of fibrovascular membrane, resulted in some surgical complications. The cases having intravitreal bevacizumab for shorter time did not show extensive fibrosis. The pretreatment of bevacizumab is likely effective in the vitrectomy for severe PDR. The appropriate timing of vitrectomy after bevacizumab injection should be further evaluated.

Purpose: The effects of oxygen supplementation status and other clinical risk factors on the development of severe retinopathy of prematurity (ROP) were evaluated. Methods: Clinical records of 143 newborn infants with a gestational age of 32 weeks or less were reviewed. Severe ROP was diagnosed when photocoagulation due to progression to stage 3 was identified or when ‘plus disease' developed. The factors were evaluated with univariate and multivariate logistic regression analyses between the groups with severe (n = 24) and non-severe (n = 119) ROP. Results: Gestational age, birth weight, duration of oxygen supplementation, duration of directional positive air pressure and maximum fraction of inspiratory oxygen (FiO2) were significantly associated with severe ROP in the univariate analyses. In the multivariate analysis, a longer duration of oxygen supplementation and a higher maximum FiO2 were revealed as significant risk factors associated with severe ROP. Conclusions: Duration of oxygen supplementation and maximum FiO2 required were important factors associated with severe ROP.

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 0.17mmoll-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., 加齢黄斑変性の発症に関わるアジア人特有の遺伝子変異を発見. 京都大学プレスリリース. 2015-02-05., Updated 30 March 2015. [Corrigendum] doi:10.1038/ncomms7817

Aim: To compare and evaluate the transitions in retinal function after photodynamic therapy (PDT) between age-related macular degeneration (AMD) and polypoidal choroidal vasculopathy (PCV) using multifocal electroretinograms (mfERGs). Methods: 10 eyes with choroidal neovascularisation (CNV) secondary to AMD and 11 eyes with CNV secondary to PCV were included in the study. mfERGs were recorded before PDT, and 1 week and 3 months after PDT. mfERG recordings were acquired by a Veris system (V.3.1.3) using a 103 hexagon stimulus. The first-order kernel was used to calculate amplitudes and latencies. Mean amplitudes and latencies from two central rings rated 0–4° of visual angle were analysed and compared with each disease. Results: In AMD, the mean first negative peak (N1) amplitudes tended to decrease, and the mean first positive peak (N1P1) amplitudes reduced to significant levels (p = 0.047) 1 week after PDT. 3 months after PDT, there were no significant differences in the mean N1 and N1P1 amplitudes compared with pre-PDT values. In PCV, there were no significant changes in the mean N1 and N1P1 amplitudes 1 week after treatment. However, 3 months after PDT, mean amplitudes showed significant increases in N1 (p = 0.008) and N1P1 (p = 0.006) amplitudes compared with pre-PDT values. Conclusions: mfERG recording transitions are different between patients with AMD and those with PCV. In patients with AMD, these results may show transient impairments in retinal function 1 week after PDT, but in those with PCV, the efficacy of PDT is superior to the impairment after PDT.

Aim: To determine the transcriptional proximity of retinal pigment epithelium (RPE) cells grown under different culture conditions and native RPE. Methods: ARPE-19 cells were grown under five conditions in 10% CO2: “subconfluent” in DMEM/F12 + 10% FBS, “confluent” in serum and serum withdrawn, and “differentiated” for 2.5 months in serum and serum withdrawn medium. Native RPE was laser microdissected. Total RNA was extracted, reverse transcribed, and radiolabelled probes were hybridised to an array containing 5353 genes. Arrays were evaluated by hierarchical cluster analysis and significance analysis of microarrays. Results: 78% of genes were expressed by native RPE while 45.3–47.7% were expressed by ARPE-19 cells, depending on culture condition. While the most abundant genes were expressed by native and cultured cells, significant differences in low abundance genes were seen. Hierarchical cluster analysis showed that confluent and differentiated, serum withdrawn cultures clustered closest to native RPE, and that serum segregated cultured cells from native RPE. The number of differentially expressed genes and their function, and profile of expressed and unexpressed genes, demonstrate differences between native and cultured cells. Conclusions: While ARPE-19 cells have significant value for studying RPE behaviour, investigators must be aware of how culture conditions can influence the mRNA phenotype of the cell.

We report a monochorionic diamniotic twin pair born at 29 weeks of gestation in which both twins developed severe retinopathy of prematurity (ROP) with retinal detachment. The pregnancy was terminated due to reversal of donor-recipient phenotypes in possible TTTS. Both twins had unstable cardiopulmonary status during the first week, and developed chronic lung disease. The larger twin, born at 1372 g, developed stage 4a ROP in both eyes, and the smaller twin, born at 1168 g, developed stage 4a ROP in the left eye. Genetic analysis of NDP, FZD4, LRP5, TSPAN12 genes revealed no mutations; however, VEGF gene polymorphism analysis showed heterozygous carrier state of the VEGF 936T allele in both twins, which is a risk factor for threshold ROP in Japanese newborn infants. We speculate the synergistic effects of unstable perinatal cardiopulmonary status and genetic predisposition due to VEGF 936C>T polymorphism caused the development of severe ROP with retinal detachment.

Aims: To determine if mild hyperoxia induces senescence in retinal pigment epithelium (RPE) cells in vitro. Methods: RPE340 cells and WI38 cells were grown in 20% oxygen and 40% oxygen until proliferative exhaustion. A combined senescence associated β galactosidase (SABG) and 5-bromo-2`-deoxyuridine (BrdU) double labelling technique was performed at different times and labelled cells were counted. Results: Cells grown in 40% oxygen stopped proliferating at an earlier population doubling level than when grown in 20% oxygen. An increase in SABG positive cells and decrease of BrdU positive cells in 40% oxygen developed at an earlier time than when grown in 20% oxygen. Conclusion: Mild hyperoxia induces premature senescence in a specific RPE cell line.

Aim: This study was conducted to evaluate the possible clinical and genetic indicators for an early response to intravitreal ranibizumab (IVR) in exudative age-related macular degeneration (AMD). Patients & methods: The records of 120 eyes from 120 Japanese patients with treatment-naive exudative AMD were retrospectively reviewed. Three consecutive IVR treatments were performed every month. Achievement of anatomical resolution was evaluated by ophthalmoscopy and optical coherence tomography. Multivariable logistic regression analysis was conducted by analyzing SNPs in the ARMS2 locus (A69S) and in the CFH gene (I62V and Y402H), in addition to clinical factors. Results: The mean central retinal thickness of overall patients was significantly decreased (-120.1 ± 122.8 µm, p = 2.7 × 10-19) at 3 months after the initial treatment. In the logistic regression analysis, the poor anatomical resolution of the lesion at 3 months was associated with the combination of CFH I62V + CFH Y402H variants (p = 0.0021), and the polypoidal choroidal vasculopathy lesions (p = 0.044). Conclusion: The CFH variants and the polypoidal choroidal vasculopathy lesion may influence the early anatomical resolution with IVR in exudative AMD. Original submitted 30 September 2013; Revision submitted 13 March 2014

To report a case of familial exudative vitreoretinopathy (FEVR) rapidly resolved by intravitreal injection of bevacizumab.A 36-year-old woman complained about floaters and visual field defect. Funduscopic examinations revealed retinal vessel anastomosis located between the equator and ora serrata in both eyes. The right eye was accompanied with slight vitreous hemorrhage. Since the patient declined retinal cryopexy for cosmetic reasons, intravitreal bevacizumab injections (1.25 mg/0.05 ml) were performed in both eyes.Treatment resulted in the rapid regression and the accelerated fibrosis of neovascular tissues. At 4-month follow-up in the right eye and 1-month follow-up in the left, no signs of systemic or ocular complications were detected.Intravitreal injection of bevacizumab may be considered as an alternative method in treating FEVR.

To clarify whether nitric oxide synthase (NOS) is involved in development of myopia, we examined the influence of form deprivation on the expressions of NOS isoform mRNA.NOS isoform cDNAs were amplified from total RNA extracted from control and 7-day-form-deprived chick retina-RPE (retinal pigment epithelium)-choroid, using competitive RT-PCR (reverse-transcription polymerase chain reaction). Each NOS isoform protein was also analyzed by Western blotting and immunohistochemistry.Expression of inducible NOS (iNOS) mRNA was highest in the control chick retina-RPE-choroid, followed by the expression of brain NOS (bNOS) mRNA. Expression of endothelial NOS (eNOS) mRNA was faint. The iNOS protein level, however, was only slightly higher than the levels of the bNOS and eNOS proteins and was found mainly in the outer part of the photoreceptor layer and inner and outer parts of RPE and choroid. bNOS alone was found in the outer nuclear layer. Although form deprivation reduced the iNOS and bNOS mRNA expressions, only the iNOS protein showed significant reduction.All three NOS isoforms were expressed in chick retina-RPE-choroid. Predominant expression of iNOS, instead of bNOS and eNOS, suggested the existence of ocular tissue-specific regulation of the iNOS gene. In addition to differences in expression level, bNOS displayed regional differential expression. Moreover, only iNOS was reduced in response to form deprivation. It is suggested that NOS isoforms may be differentially involved in the mechanisms regulating the posterior eye tissues, including myopic eye growth.

Purpose: To investigate the incidence of and risk factors for a dissociated optic nerve fiber layer (DONFL) appearance after pars plana vitrectomy (PPV). Methods: We retrospectively reviewed 189 eyes that underwent PPV with internal limiting membrane removal and judged the presence/absence of an apparent DONFL based on en face layer images produced by spectral-domain optical coherence tomography (SD-OCT). Results: An apparent DONFL was observed in 47 (24.9%) eyes. The incidence of an apparent DONFL was significantly higher in the macular hole (MH) group (76.5%) than in the non-MH group (epiretinal membrane, diabetic macular edema, retinal vein occlusion, and others; 4.9%; p < 0.001). In the logistic regression analysis, surgical indication for MH was identified as the most significant DONFL risk factor (odds ratio 63.7; p = 1.05 × 10-8). Conclusion: Postoperative OCT en face layer imaging clarified that MH eyes are liable to have an apparent DONFL following PPV.

To investigate the effects of reproducibility of optical coherence tomography (OCT) measurements and imaging alignment on predictive performance for visual outcome following macular hole (MH) surgery. We retrospectively reviewed 50 eyes that underwent MH surgery. Preoperative cross-sectional images through the center of the MH (on-center image) and through an off-center point (off-center image) were obtained from the OCT data. In each image, the following OCT parameters were either measured or calculated: minimum diameter, base diameter, hole height, temporal and nasal arm length, photoreceptor inner segment/outer segment (IS/OS) defect length, the hole form factor, the macular hole index and the tractional hole index. The IS/OS defect area was also measured. The reproducibility of OCT parameter values was moderate to high, and there was a significant difference in the mean measurement values between the on- and off-center images. Predictive values varied between sessions and raters, and only the preoperative photoreceptor IS/OS defect length consistently showed significant correlation with postoperative visual outcome. 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.

Background The 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). Methods This 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. Results The mean BCVA was significantly improved (-0.11 logMAR units) at month 3 after the initial IVR (p Conclusions IVR 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.

Yoshihiro Nishimura1,2, Maiko Taguchi1, Takafumi Nagai1, Masashi Fujihara1,2, Shigeru Honda2, Mamoru Uenishi11Department of Ophthalmology, Mitsubishi Kobe Hospital, Kobe, Japan; 2Department of Surgery, Division of Ophthalmology, Kobe University Graduate School of Medicine, Kobe, JapanPurpose: To compare the effect of pegaptanib versus ranibizumab on exudative age-related macular degeneration (AMD) with small lesion size.Methods: This is a retrospective study of 81 eyes from 78 patients with exudative AMD treated and followed up over 12 months. Patients with baseline best corrected visual acuity (BCVA) under 20/400 and with a greatest linear dimension of lesion over 4500 µm were excluded from the study. Twenty-six eyes from 25 patients were treated with three consecutive intravitreal injections of pegaptanib (IVP group) and 55 eyes from 54 patients were treated with three consecutive ranibizumab injections (IVR group). Each therapy was repeated as needed. The alteration in BCVA was evaluated in the IVP and IVR groups.Results: No differences were detected in baseline parameters between the IVP and IVR groups. The mean BCVA (logMAR) at month 1, 3, 6 and 12 after the initial treatment was improved from baseline in the IVP group (-0.095, -0.17, -0.18 and -0.18, respectively) and in the IVR group (-0.077, -0.15, -0.17 and -0.11, respectively), which was statistically significant. There was no difference in the change in mean BCVA between IVP and IVR groups at the same time periods.Conclusions: The visual outcome of IVP was equivalent with IVR in exudative AMD with small lesion size.Keywords: pegaptanib, ranibizumab, age-related macular degeneration, small lesion size

BACKGROUND: Genetic 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 (

Purpose: To evaluate the natural course and possible funduscopic risk factors for polypoidal choroidal vasculopathy in a Japanese population. Methods: The records of 42 eyes from 41 patients (27 men and 14 women) diagnosed as having polypoidal choroidal vasculopathy located in the macula between November 1999 and October 2005 were retrospectively reviewed. The funduscopic findings at the first visit were evaluated. The changes in the best-corrected visual acuity (BCVA) from the baseline to 12 months were analyzed. The lesion types (clustered vs. nonclustered) found on indocyanine green angiography were compared for changes in the BCVA from the initial visit to 12 months. Results: The mean age of the subjects was 73.8 ± 8.0 years. The mean logarithm of the minimum angle of resolution (LogMAR) BCVA was 0.48 ± 4.0 at baseline and deteriorated to 0.75 ± 5.7 after 12 months, which was statistically significant (P = 0.00075). The mean LogMAR BCVA in the patients showing “nonclustered” polypoidal choroidal lesions on indocyanine green angiography was maintained for 12 months, while that of the “clustered” group decreased significantly during the same period (P = 0.0014). Conclusion: Polypoidal choroidal vasculopathy did not show a favorable outcome in terms of the mean BCVA 12 months after the initial visit. The clustered polypoidal choroidal lesions on indocyanine green angiography may be related to poor prognosis of polypoidal choroidal vasculopathy over the natural course.

To compare the efficacy of anti-vascular endothelial growth factor (VEGF) therapy versus photodynamic therapy (PDT) for myopic choroidal neovascularization (mCNV).This study is a retrospective interventional study. Forty-two eyes from 42 patients with mCNV (36 subfoveal, 4 juxtafoveal, and 2 extrafoveal) treated and followed up for more than 6 months were included. Twenty eyes from 20 patients were treated by PDT (PDT group) at 1.5 ± 0.9 months after the symptoms and 22 eyes from 22 patients were treated by anti-VEGF therapy (anti-VEGF group) at 0.9 ± 0.8 months after the symptoms. Photodynamic therapy was performed, followed up, and retreated by standard procedures. Anti-VEGF therapy was repeated as needed. Gender, age, best-corrected visual acuity (BCVA), greatest linear dimension (GLD), central retinal thickness (CRT), and outer nuclear layer (ONL) thickness at the fovea were then compared between the anti-VEGF and PDT groups.No differences were detected in baseline parameters between the anti-VEGF and PDT groups. The mean BCVA (logMAR) at month 3 and 6 after the initial treatment was improved (-0.30 and -0.29) from baseline in the anti-VEGF group, which was statistically significant (p=0.0048 and 0.021, respectively). In the PDT group, modest improvements were observed in the mean BCVA at the same time periods (-0.05 and -0.10) with no statistical significance (p=0.79 and 0.90, respectively). The mean CRT was significantly reduced from baseline to month 6 in the anti-VEGF and PDT groups. The ONL thickness was significantly reduced in both groups, although the magnitude was significantly greater in the PDT group than the anti-VEGF group.Treatment with anti-VEGF therapy had significantly better visual outcomes than PDT for mCNV.