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PURPOSE To study the association between the risk of massive submacular hemorrhage (SMH) and polyp regression after initial treatment of polypoidal choroidal vasculopathy using long-term follow-up data. METHODS Retrospective study of 223 patients who were diagnosed with polypoidal choroidal vasculopathy and were followed up for up to 11 years. Subjects were categorized into "regression" and "no regression" groups, according to their polyp status after the initial treatment. Kaplan-Meier survival analyses were performed on development of massive SMH. The association between treatment methods and the occurrence of massive SMH was also analyzed. RESULTS The incidence rates of massive SMH at 3, 6, and 9 years in the "no regression" group were 6.50, 22.59, and 38.03%, respectively, and in the "regression" group were 1.14, 6.47, and 10.92%, respectively (P = 0.005, log-rank test). The hazard ratio of massive SMH was 3.677 for cluster-type polyps and 0.271 for polyp regression after initial treatment. A higher rate of polyp regression was associated with photodynamic therapy (PDT) than anti-VEGF monotherapy (64.4 vs. 33.3%, P < 0.001). Additional anti-VEGF treatments after initial PDT showed lower risk of massive SMH than PDT only. (9.5 vs 38.5%, P = 0.005). CONCLUSION The long-term risk of massive SMH after initial treatment on polypoidal choroidal vasculopathy is significantly higher in eyes with persistent polyps than those with regressed polyps. Ophthalmologists should pay attention to the risk of massive SMH and the polyp status when treating polypoidal choroidal vasculopathy.

We evaluated phenotype and genotype correlation of central serous chorioretinopathy (CSC) patients with or without irregular pigment epithelial detachment (PED) on optical coherence tomography (OCT). For CSC, a flat, irregular protrusion of retinal pigment epithelium (RPE) with hyper-reflective sub-RPE fluid on OCT was defined as an irregular PED. Participants were classified into 5 subgroups; (1) total CSC (n = 280) (2) CSC with irregular PED (n = 126) (3) CSC without irregular PED (n = 154) (4) typical choroidal neovascularization (CNV) (n = 203) and (5) polypoidal choroidal vasculopathy (PCV) (n = 135). Ten known major AMD-associated single-nucleotide polymorphisms (SNPs) were analyzed. Age, sex adjusted logistic regression was performed for the association between subgroups. Association analysis between CSC without irregular PED and CNV revealed that significant difference for rs10490924 in ARMS2, rs10737680 in CFH, and marginally significant difference for rs800292 in CFH. Between CSC without irregular PED and PCV, rs10490924, rs10737680, and rs800292 were significantly different. In contrast, CSC with irregular PED and CNV revealed no SNP showing significant difference. Between CSC with irregular PED and PCV, only rs10490924 was significantly different. CSC with irregular PED and CSC without irregular PED revealed significant difference for rs800292, and marginal difference for rs10737680. These findings suggest CSC patients with irregular PED are genetically different from those without irregular PED and may have genetic and pathophysiologic overlap with AMD patients.

Purpose VEGF-Grab is a novel anti-vascular endothelial growth factor (VEGF) candidate drug with higher affinity to both VEGF and placental growth factor (PlGF) compared to aflibercept. We investigated the preclinical efficacy of VEGF-Grab for ophthalmic therapy and compared it to that of aflibercept. Methods The in vitro anti-VEGF efficacy of VEGF-Grab was determined using VEGF-induced cell proliferation/migration and tube formation assays. The in vivo antiangiogenic efficacy of intravitreal injection of either VEGF-Grab or aflibercept was evaluated using murine models of ocular angiogenesis: mouse oxygen-induced retinopathy (OIR) and rat laser-induced choroidal neovascularization (CNV). The in vivo retinal toxicity in the mouse eye resulting from the injection of either drug was evaluated with light and electron microscopy. Results VEGF-Grab showed greater inhibition of VEGF-induced cell proliferation/migration than aflibercept, but it showed comparable inhibition of tube formation in vitro. In the in vivo OIR model, VEGF-Grab showed a comparable suppression of retinal neovascularization compared to aflibercept. Additionally, VEGF-Grab showed an efficacy similar to that of aflibercept in terms of CNV inhibition in the laser-induced CNV model. Histology and transmission electron microscopy showed no significant signs of toxicity in the mouse retina at 7 and 30 days following the intravitreal injection of VEGF-Grab or aflibercept. Conclusions Compared to aflibercept, VEGF-Grab presented comparable in vivo antiangiogenic efficacy and superior in vitro anti-VEGF activity. The retinal safety profiles were comparable for the two drugs. Considering its known higher binding affinity to VEGF and PlGF compared to aflibercept, VEGF-Grab could be a potential candidate drug for neovascular retinal diseases and an alternative to aflibercept.

Purpose To investigate the incidence rate of massive submacular hemorrhage (SMH) in patients with polypoidal choroidal vasculopathy (PCV) and analyze the associated risk factors. Design Retrospective cohort study. Methods Patients diagnosed with PCV from May 2003 to May 2014 were included. Two hundred forty-five eyes of 245 patients were enrolled. The time between the initial visit to the clinic with subjective visual symptoms and the date of massive SMH was recorded. SMH larger than 4 disc diameters was defined as massive SMH. Age; hypertension; visual acuity (VA); indocyanine green angiography findings, including the greatest linear dimension, largest polyp size, and PCV type (cluster vs non-cluster); and treatment methods were reviewed for risk factor analysis using Kaplan-Meier survival and Cox regression analyses. Results The incidence rate of massive SMH within 1 year after the initial visit was 2.45%. Massive SMH occurred within 3, 5, and 10 years after the first visit in 6.17%, 11.09%, and 29.85% of patients, respectively. Cox regression analysis revealed that the cluster type of PCV was significantly associated with massive SMH (hazard ratio [HR], 3.418; P = .003). Photodynamic therapy followed by anti–vascular endothelial growth factor injection lowered the risk of massive SMH (HR = .242; P = .047]. Final VA in eyes with massive SMH was significantly lower than that in patients without massive SMH (1.34 ± 0.66 vs 0.63 ± 0.53 logMAR; P Conclusions Patients with PCV who develop massive SMH experience severe vision loss. The incidence rate of massive SMH in PCV increases with time. The cluster type of polyp in PCV is a significant risk factor for massive SMH.

PURPOSE To compare the efficacy between 23-gauge sutureless pars planar vitrectomy (PPV) and anterior vitrectomy in the management of vitreous loss associated with posterior capsular rupture during cataract surgery. METHODS Medical records of 139 eyes which sustained posterior capsular rupture and vitreal prolapse to anterior chamber during cataract surgery were retrospectively reviewed. Thirty-two eyes which underwent 23-gauge sutureless PPV (group PPV) and 107 eyes which underwent anterior vitrectomy (group AntV) were compared in postoperative visual and anatomical outcomes, operation time, and complications. RESULTS No significant differences were found between the groups in final best-corrected visual acuity of 20/40 or better (AntV vs. PPV = 80.4 vs. 90.6%, P = 0.139). However, the visual recovery rates (20/40 or better) 1 day, 1 week, 1 month postoperatively were significantly higher in group PPV (AntV vs PPV = 22.4 vs. 44%, 32.2 vs 58.6, 51.9 vs. 78.1%). Postoperative intraocular pressure-related complications requiring medication were less evident in group PPV (AntV vs. PPV = 52.3 vs. 6.3%, P < 0.001). Twelve cases (11.2%) of group AntV and 0 cases of group PPV underwent secondary operation during follow-up. Although no postoperative complications occurred in group PPV, complications such as endophthalmitis, retinal detachment, cystoid macular edema, intraocular lens instability were observed in the AntV group (none vs. 14%, P = 0.022). CONCLUSION Twenty-three-gauge sutureless PPV is a safe and reliable solution for managing vitreous loss during cataract surgery. Therefore, it is expected to be considered primarily in institutes with vitreoretinal surgeons.

PurposeTo analyze the associations of retinal and choroidal thickness on enhanced-depth imaging optical coherence tomography (EDI-OCT) with clinical, ophthalmic and genetic factors in the normal elderly population (aged 65 years or older).MethodsIn this prospective, population-based cohort study, people aged 65 years or older were enrolled in the baseline study of the Korean Longitudinal Study on Health and Aging (KLoSHA) Eye Study. All participants underwent spectral domain-OCT scan using the EDI technique. A topographic map of the retina was obtained and subfoveal choroidal thickness (SFCT) was measured manually. Blood samples from all subjects were genotyped for major age-related macular degeneration (AMD)-associated single nucleotide polymorphisms (SNPs) the major AMD-associated SNPs; CFH Y402H rs1061170, CFH I62V rs800292, ARMS2 A69S rs10490924. A statistical analysis was conducted to compare the retinal thickness, choroidal thickness, and AMD risk genotypes.ResultsAmong the three hundred eighty people enrolled, the mean age was 76.6 years (range 65-99 years). Factors that showed correlation with either tomographic retinal parameters, retinal nerve fiber layer, or SFCT, were age and gender. Significant age-related decrease in thickness was observed in the RNFL, mean central thickness (MCT) and SFCT. Gender differences existed in central foveolar thickness (CFT) and MCT, where it was thicker in men. While chorioretinal parameters were not related with other genotypes, CFH rs1061170 risk genotype was significantly associated with thin SFCT. The group containing the AMD- risk allele (CT) had a 14.7% reduction in the SFCT compared to the non-risk TT group.ConclusionsIn addition to the well-known association with AMD, CFH rs1061170 is a significant genetic risk factor associated with choroidal thinning in normal eyes of the elderly population. Such findings may provide further insight into the pathogenesis of age-related macular degeneration as well as normal aging. In addition, our study provides the first normative data on retinal and choroidal thickness in population-based aged groups with a mean age over seventy-five.

To describe three cases of neovascular glaucoma (NVG) where iris or angle neovascularization regressed remarkably after subconjunctival bevacizumab injections used as the initial treatment before pan retinal photocoagulation (PRP) and/or filtering surgery. Three consecutive NVG patients whose intraocular pressure (IOP) was not controlled with maximal medication were offered an off-label subconjunctival injection of bevacizumab (2.5-3.75 mg/0.1-0.15 mL, Avastin). Bevacizumab was injected into the subconjunctival space close to the corneal limbus in two or three quadrants using a 26-gauge needle. Serial anterior segment photographs were taken before and after the injection. Following subconjunctival injection of bevacizumab, iris or angle neovascularization regressed rapidly within several days. Such regression was accompanied by lowering of IOP in all three cases. The patients underwent subsequent PRP and/or filtering surgery, and the IOP was further stabilized. Our cases demonstrate that subconjunctival bevacizumab injection can be potentially useful as an initial treatment in NVG patients before laser or surgical treatment.

Age-related macular degeneration (AMD) is a major cause of severe, progressive visual loss among the elderly. There are currently no established serological markers for the diagnosis of AMD. In this study, we carried out a large-scale quantitative proteomics analysis to identify plasma proteins that could serve as potential AMD biomarkers. We found that the plasma levels of phospholipid transfer protein (PLTP) and mannan-binding lectin serine protease (MASP)-1 were increased in AMD patients relative to controls. The receiver operating characteristic curve based on data from an independent set of AMD patients and healthy controls had an area under the curve of 0.936 for PLTP and 0.716 for MASP-1, revealing excellent discrimination between the two groups. A proteogenomic combination model that incorporated PLTP and MASP-1 along with two known risk genotypes of age-related maculopathy susceptibility 2 and complement factor H genes further enhanced discriminatory power. Additionally, PLTP and MASP-1 mRNA and protein expression levels were upregulated in retinal pigment epithelial cells upon exposure to oxidative stress in vitro. These results indicate that PLTP and MASP-1 can serve as plasma biomarkers for the early diagnosis and treatment of AMD, which is critical for preventing AMD-related blindness.

We investigated morphologic features of choroid in the choroidal thickening diseases, including central serous chorioretinopathy (CSC), polypoidal choroidal vasculopathy (PCV), and Vogt-Koyanagi-Harada disease (VKH), by a novel tomographic classification system of the choroid. This cross-sectional study involved 30 patients with active CSC, 30 patients with active PCV, and 27 patients with active VKH, and 30 normal controls. Utilizing enhanced depth imaging optical coherence tomography, we classified the morphology of the choroid into five categories: 1) Standard (S), 2) Dilated outer layer and Attenuated inner layer (DA), 3) Darkened (D), 4) Marbled (M), and 5) Pauci-Vascular (PV) types. Additional tomographic characteristics of the choroid such as choroidal vascular dilation, convolution, scleral invisibility, and choroidal hyper- or hypo-thickening were identified as well. The distribution of five choroidal tomographic morphology and additional tomographic characteristics in each group were analyzed. The DA type was observed in the CSC group more frequently than in the normal control group (53.3% vs 3.3%, P < 0.001). Additional tomographic characteristics, such as choroidal vascular dilation (76.7%), and choroidal hyper-thickening (36.7%), were more prevalent in the CSC group than in the control group. The PCV group showed higher prevalence of DA type (33.3% vs. 3.3%, P = 0.006) than the control group. The VKH group showed a significantly higher frequency of the D type (63.0%), convolution (40.7%), and scleral invisibility (70.4%) than controls (0% for all three findings). In conclusion, CSC and PCV shared common morphologic characteristics of choroid, including dilated outer vascular layer and focally attenuated innermost layer. Dense hypo-reflectivity and convolution of choroid were the specific tomographic markers for acute VKH. A new tomographic classification system of choroid may provide discrimination ability and insight into major pachychoroidopathies.

Purpose To investigate the incidence and risk factors of the no-reflow phenomenon in central retinal artery occlusion (CRAO) patients and to determine its effects on visual and anatomic outcomes. Methods In 102 eyes with CRAO in which arterial recanalization was obtained within 1 week from baseline, fluorescein angiography images obtained at baseline and 1 week were retrospectively reviewed. The no-reflow phenomenon in the retina was defined as macular capillary nonperfusion following arterial recanalization on fluorescein angiographs. We investigated the incidence and risk factors for the no-reflow phenomenon and compared the anatomical and visual outcomes between eyes with and without the phenomenon. Results Among the 102 CRAO eyes with arterial recanalization, 39 exhibited the no-reflow phenomenon, resulting in an incidence of 38.2%. The incidence among the eyes with treatment-induced and spontaneous recanalization was 43.4% and 15.8%, respectively, and it increased with the CRAO stage. CRAO stage and increased central macular thickness were risk factors for the phenomenon, with an odds ratio of 4.47 [95% confidence interval (CI), 1.19-16.8; P = 0.027] and 1.69 (95% CI, 1.12-2.55; P = 0.012) per 100-μm increase, respectively. The visual outcome was significantly poorer and retinal atrophy and photoreceptor disruption was greater in eyes with the no-reflow phenomenon than in those without. Conclusions The no-reflow phenomenon may occur after arterial recanalization in approximately one-third of CRAO patients and can affect anatomical and visual outcomes. This phenomenon may provide an additional explanation regarding the permanent retinal damage and vision loss in eyes with CRAO.

To compare visual and anatomical outcomes of half-fluence (HF) and half-dose (HD) photodynamic therapy (PDT) in chronic central serous chorioretinopathy (CSC). Particular focus was given to photoreceptor recovery rate following treatment. Retrospective review of 52 chronic CSC patients who underwent HF- or HD-PDT (26 patients per group). Best-corrected visual acuity and spectral-domain optical coherence tomography findings were compared between groups. Average follow-up for HF- and HD-PDT was 20.7 ± 7.2 and 22.3 ± 6.1 months respectively. Both groups had significant visual acuity improvements, as well as central foveal and subfoveal choroidal thickness reductions. Measured parameters were not significantly different between groups at any time point examined. Complete photoreceptor recovery, defined as a continuous ellipsoid zone with a discernible interdigitation zone, was observed at 12 months in 19 (73 %) and 14 patients (54 %) in the HF- and HD-PDT groups respectively (p = 0.150). Overall photoreceptor recovery rate was not different between groups (p = 0.301, log-rank test). Delayed (>12 months) photoreceptor recovery was significantly associated with baseline external limiting membrane disruption (OR: 21.7, 95 % CI: 1.7–285.4, p = 0.019), disease duration (years, OR: 1.9, 95 % CI: 1.2–3.0, p = 0.005), and fovea-to-PDT spot center distance (100 μm unit, OR: 0.74, 95 % CI 0.56–0.97, p = 0.027). However, delayed photoreceptor recovery was not significantly associated with PDT modality. Both HF- and HD-PDT are effective in treating chronic CSC. No significant differences in visual or anatomical outcomes were observed.

Infectious sources have been repeatedly reported as the pathogenesis in various cancers. The relationship between the human papilloma virus (HPV) and cervical cancer is a well-proven example. Especially among the various types of HPV, certain types appear to be more oncogenic and are therefore named high-risk HPV [1]. Helicobacter pylori and gastric cancer is another widely-known example of infective agent-associated cancer [2]. Based on such findings, microorganism or viral eradication has been suggested as a treatment for such cancers. In the same vein, interest has arisen in the association of ocular tumors and infections. The association between ocular adnexal mucosa-associated lymphoid tissue lymphoma and Chlamydia psittaci infection has been well documented [3]. Among ocular tumors, retinoblastoma (RBL) is the most common primary ocular malignancy in children, accounting for approximately 3% of the tumors occurring in people under 15 years of age and leading to 9,000 deaths annually worldwide [4]. RBL is known to be more prevalent in areas of low hygiene and socioeconomic status, such as South America, Africa and Southeast Asia, raising the possibility of infection as a factor in its development. Several studies have recently reported the association of HPV with RBL. Anand et al. [5] demonstrated the presence of HPV in a subset of patients with RBL. Shetty et al. [6] also suggested that infection of HPV-16/-18 may interfere with the cell regulatory process and lead to development of RBL in the Indian population. However, contradictory results were reported by Gillison et al. [7] that revealed no relationship between HPV and RBL in North American populations. These discrepant results may suggest geographic differences in the prevalence and etiology of retinoblastoma and HPV infection. To date, no reports are available with respect to the East Asian population. In this study, we analyzed 54 retinoblastoma patients who underwent enucleation to demonstrate the association with HPV infection in the Korean population.