Title: Pachydrusen in Fellow Eyes Predict Response to Aflibercept Monotherapy in Patients with Polypoidal Choroidal Vasculopathy.

We investigated whether responses to as-needed intravitreal aflibercept injections (IAIs) for polypoidal choroidal vasculopathy (PCV) differed among patients based upon drusen characteristics in fellow eyes. 110 eyes from 110 patients with PCV received 3 monthly IAI and thereafter Pro re nata (PRN) IAI over 12 months. Patients were classified into 4 groups depending on fellow eye findings. Group 1 (n = 16): pachydrusen; Group 2 (n = 45): no drusen; Group 3 (n = 35): soft drusen; Group4 (n = 14) PCV/scarring. Best-corrected visual acuity improved at 12 months in all groups, but not significantly in Group 1 and Group 4; however, visual improvement was similar among the groups after adjusting baseline confounders. Group 1 had a significantly lower percentage of eyes needing retreatment (all p < 0.001; Group 1: 16.7%; Group 2: 50.8%; Group 3: 80%; Group 4: 85.7%). The mean number of retreatments was least in Group 1 among the groups (all p-value < 0.003; Group 1: 0.50 ± 1.32; Group 2: 1.73 ± 2.08; Group 3:2.71 ± 1.99; Group 3: 2.71 ± 2.16). Patients with pachydrusen in fellow eyes were less likely to require additional IAI following the loading dose and may be ideal candidates for aflibercept monotherapy in their first year.

Association of CRP levels with ARMS2 and CFH variants in age-related macular degeneration.

PURPOSE: To investigate whether plasma high sensitivity C-reactive protein (hs-CRP) level is associated with exudative age-related macular degeneration (AMD) as well as variants of ARMS2 A69S and CFH I62V in patients with exudative AMD. METHODS: A case-control study was done comparing CRP among patients with exudative AMD including those with polypoidal choroidal vasculopathy, typical AMD and retinal angiomatous proliferation, and CRP were also compared between cases and controls. Plasma CRP was measured from peripheral blood using latex nepherometry for all participants. Genotyping of ARMS2 A69S and CFH I62V was performed for all patients with exudative AMD using TaqMan technology. RESULTS: Among 125 patients with exudative AMD, including 31 with typical neovascular AMD, 73 with PCV and 21 with RAP lesions and 150 controls, CRP levels were higher in exudative AMD than in controls. (P = 2.7 × 10-5) There was not a significant difference in hs-CRP levels among AMD subtypes. Neither variants of ARMS2 nor CFH was associated with hs-CRP level in patients with exudative AMD. A multiple regression analysis revealed that gender male, presence of exudative AMD and presence of cardiovascular diseases were associated with increased plasma hs-CRP. CONCLUSIONS: Plasma hs-CRP was elevated independent of variants of ARMS2 A69S and CFH I62V in patients with exudative AMD.

Genetic factors associated with response to as-needed aflibercept therapy for typical neovascular age-related macular degeneration and polypoidal choroidal vasculopathy.

In the present study, we investigated the association between susceptible genetic variants to age-related macular degeneration (AMD) and response to as-needed intravitreal aflibercept injection (IAI) therapy for exudative AMD including both typical neovascular AMD and polypoidal choroidal vasculopathy (PCV) over 12-months. A total of 234 patients with exudative AMD were initially treated with 3 monthly IAI and thereafter as-needed IAI over 12 months. Seven variants of 6 genes including ARMS2 A69S (rs10490924), CFH (I62V:rs800292 and rs1329428), C2-CFB-SKIV2L(rs429608), C3 (rs2241394), CETP (rs3764261) and ADAMTS-9 (rs6795735) were genotyped for all participants using TaqMan technology. After adjusting for age, gender, baseline BCVA and AMD subtype, A (protective) allele of C2-CFB-SKIV2L rs429608 was associated with visual improvement at 12-month (P = 0.003). Retreatment was associated with T(risk) allele of ARMS2 A69S (P = 2.0 × 10-4; hazard ratio: 2.18:95%CI: 1.47-3.24) and C(risk) allele of CFH rs1329428 (P = 2.0 × 10-3; hazard ratio: 1.74:95%CI: 1.16-2.59) after adjusting for the baseline confounders. The need for additional injections was also associated with T allele of ARMS2 A69S (P = 1.0 × 10-5) and C allele of CFH rs1329428 (P = 3.0 × 10-3) after adjusting for the baseline confounders. The variants of ARMS2 and CFH are informative for both physicians and patients to predict recurrence and to quantify the need for additional injections.

Clinical and genetic characteristics of pachydrusen in patients with exudative age-related macular degeneration.

We investigated the clinical and genetic characteristics of patients with unilateral exudative age-related macular degeneration (AMD), including typical AMD, polypoidal choroidal vasculopathy, and retinal angiomatous proliferation, in whom pachydrusen was seen. Patients with unilateral exudative AMD with at least a 12-month follow-up period were included. According to the fellow eye condition, 327 consecutive patients were classified into 4 groups: Group 0: no drusen (42.8%), Group 1: pachydrusen (12.2%), Group 2: soft drusen (30.3%), Group 3: pseudodrusen with or without soft drusen (14.7%). Development of exudative AMD in the fellow eye was retrospectively studied for a 60-month period and this inter-group comparisons were performed. Genotyping was performed for ARMS2 A69S and CFH I62V. The thickness of the choroid in the fellow eyes increased significantly in Group 1 than in other groups (all P < 1.0 × 10-7). The development of exudative AMD in the fellow eye was significantly less frequent in Group 1 than in Groups 2 or 3 (P = 0.022 and 0.0015, respectively). Risk allele frequency of ARMS2 A69S was significantly lower in Group 1 than in Group 2 and 3 (all P < 1.0 × 10-4). Patients with pachydrusen have genetic and clinical characteristics distinct from those of soft drusen and pseudodrusen.

Pseudodrusen pattern and development of late age-related macular degeneration in the fellow eye of the unilateral case.

PURPOSE: To investigate whether the development of late age-related macular degeneration (AMD) in fellow eyes with pseudodrusen is associated with the pseudodrusen pattern in patients with unilateral exudative AMD. STUDY DESIGN: Retrospective observational study. METHODS: A retrospective analysis was performed on 73 patients with unilateral exudative AMD showing pseudodrusen in their fellow eyes. Eyes were classified according to pseudodrusen pattern, which was determined based on maximum pseudodrusen ribbon length. RESULTS: During the mean follow-up period of 35.5±18.6 months, 21 (28.8%) eyes developed late AMD. Among these eyes, 15 (71%) developed exudative AMD and six (29%) developed geographic atrophy (GA). Development of late AMD in fellow eyes occurred with significantly more prevalence in patients showing a ribbon-dominant type pseudodrusen pattern in their fellow eye than dot-dominant type (P=0.0005, log-rank test). Cox-regression analysis revealed that development of late AMD in fellow eyes is associated with the presence of ribbon-dominant pseudodrusen in the fellow eyes (hazard ratio 4.15, 95% confidence interval (CI) 1.59-10.8), along with older age (hazard ratio 1.10, 95% CI 1.03-1.17), a history of smoking (hazard ratio 17.2, 95% CI 1.11-263), the presence of large soft drusen in the fellow eye. (hazard ratio 5.49, 95% CI 1.29-21.1) and retinal angiomatous proliferation (hazard ratio 5.02, 95% CI 1.90-13.2) CONCLUSIONS: Fellow eyes with ribbon-dominant pseudodrusen in patients with unilateral exudative AMD are likely to develop late AMD.

AREDS simplified severity scale as a predictive factor for response to aflibercept therapy for typical neovascular age-related macular degeneration.

PURPOSE: To investigate whether the severity of the condition in the untreated fellow eye is a predictive factor for the response to intravitreal aflibercept injection (IAI) for exudative age-related macular degeneration (AMD). METHODS: A retrospective medical chart review was conducted for 88 patients with treatment-naïve neovascular AMD, who were initially treated with three monthly IAIs, followed by monthly monitoring and re-injection as needed for at least 12 months. Subjects were classified into three groups according to the severity of the condition in their untreated eye, based on the severity scale in the Age-Related Eye Disease Study (AREDS): group 0, AREDS severity level 1 (no drusen); group 1, AREDS severity level 2 or 3 (any drusen); group 2, AREDS severity level 4 (advanced AMD). Genotyping was performed in all cases for ARMS2 A69S and CFH I62V. RESULTS: Fellow-eye severity was associated with age and the risk variant of ARMS2 A69S (P = 0.005 and 0.001, respectively). Although best-corrected visual acuity (BCVA) had improved significantly after 12 months in all groups, this improvement was significantly greater in group 0 than in the other groups (P = 0.008). The retreatment-free period was also significantly longer for group 0 than for the other groups (P = 0.016), and the number of additional injections was significantly associated with fellow-eye severity (P = 0.007). CONCLUSIONS: Fellow-eye severity was associated with treatment response in terms of visual improvement and retreatment and may be a predictive factor for response to IAI for neovascular AMD.

Comparison of two-year outcomes after photodynamic therapy with ranibizumab or aflibercept for polypoidal choroidal vasculopathy.

Photodynamic therapy (PDT) combined with intravitreal anti-vascular endothelial growth factor (VEGF) agents is currently the first-line treatment for polypoidal choroidal vasculopathy (PCV), along with anti-VEGF monotherapy. In this study, 100 eyes with treatment-naïve PCV were initially treated with PDT combined with intravitreal ranibizumab (IVR; n = 57) or aflibercept (IVA; n = 43). We compared two-year outcomes between these two groups and investigated factors associated with visual improvement and retreatment over 24 months. Best-corrected visual acuity (BCVA) was significantly improved in both groups (P < 0.001) at 24 months. Multiple regression analysis revealed that visual improvement at 24 months was associated with female (P = 0.030), worse baseline BCVA (P = 3.0 × 10-6), smaller greatest linear dimension (GLD; P = 2.0 × 10-4), and treatment with IVA rather than IVR (P = 0.016). Multiple logistic regression analysis revealed that absence of retreatment was associated with younger age (P = 2.2 × 10-4), female (P = 1.2 × 10-3), and the non-risk variants of ARMS2 A69S (P = 6.0 × 10-4). Although there were no significant differences in the retreatment rate between the two groups, PDT/IVA may be superior to PDT/IVR in terms of visual improvement at 24 months.

Incidence and risk factors of retreatment after three-monthly aflibercept therapy for exudative age-related macular degeneration.

Though anti-vascular endothelial growth factor therapy has become the standard treatment for exudative age-related macular degeneration (AMD), retreatment after the initial loading injection is inevitable in most eyes with residual or recurrent exudative changes. In the present study, we studied 140 treatment naïve eyes with typical neovascular AMD (n = 71) or polypoidal choroidal vasculopathy (PCV) (n = 69) and investigated the incidence and risk factors of retreatment after 3-monthly intravitreal aflibercept injection for exudative AMD during the 12-month period. At 12 months, best-corrected visual acuity (BCVA) improved significantly from 0.45 ± 0.39 to 0.26 ± 0.33 (P = 4.1 × 10-11). Multiple regression analysis revealed that better baseline BCVA (P = 3.6 × 10-14) and thicker subfoveal choroidal thickness (P = 0.039) were associated with better BCVA at 12-months. Retreatment was required in 94 out of 140 (67.1%) eyes. Multivariate logistic regression analysis revealed that older age (P = 7.2 × 10-3) and T-allele of ARMS2 A69S (rs10490924) variants (P = 1.9 × 10-3) were associated with retreatment. Cox-regression analysis revealed that older age (P = 1.0 × 10-2) and T-allele of the ARMS2 gene (P = 6.0 × 10-3) were associated with retreatment-free period. The number of retreatment episodes was significantly different among the ARMS2 genotypes (P = 8.1 × 10-4). These findings might be helpful for physicians when considering the optimal treatment regimen for exudative AMD.

Prevalence and characteristics of pseudodrusen subtypes in advanced age-related macular degeneration.

PURPOSE: The purpose of our study was to investigate the clinical and genetic characteristics of pseudodrusen subtypes and their incidence in advanced age-related macular degeneration (AMD). METHODS: We studied 84 eyes from 84 patients with pseudodrusen associated with advanced AMD, including typical AMD, polypoidal choroidal vasculopathy (PCV), retinal angiomatous proliferation (RAP), and geographic atrophy (GA). Multiple imaging modalities, including color fundus photography, spectral-domain optical coherence tomography (SD-OCT), near-infrared reflectance, and fundus autofluorescence, were employed to diagnose pseudodrusen and its subtypes. Subfoveal choroidal thickness was measured using SD-OCT. Subject eyes were classified into two subtypes, dot-dominant or ribbon-dominant, according to the maximum length of ribbon pseudodrusen. Genotyping was performed for ARMS2 A69S (rs10490924) and CFH I62V (rs800292) variants. RESULTS: The percentage of ribbon-dominant type pseudodrusen was significantly higher in eyes with RAP (69.6%) and GA (78.6%) compared with those with typical AMD (31.1%) (p = .0025 and .0017, respectively). Multivariate logistic regression analysis disclosed that incidence of female patients and coexisting large soft drusen was significantly higher in ribbon- than dot-dominant types (P = 0.014 and P = 0.008, respectively), while age, subfoveal choroidal thickness, and risk allele frequency for both ARMS2 A69S (rs10490924) and CFH I62V (rs800292) were not different between the two pseudodrusen subtypes. CONCLUSIONS: Among eyes with advanced AMD associated with pseudodrusen, ribbon-dominant type pseudodrusen were more prevalent in eyes with GA or RAP and were associated with large soft drusen and female patients.

CHOROIDAL THICKNESS AS A PROGNOSTIC FACTOR OF PHOTODYNAMIC THERAPY WITH AFLIBERCEPT OR RANIBIZUMAB FOR POLYPOIDAL CHOROIDAL VASCULOPATHY.

PURPOSE: To investigate factors associated with visual improvement and retreatment 12 months after a combination therapy of intravitreal injection of ranibizumab or aflibercept followed by photodynamic therapy for polypoidal choroidal vasculopathy. METHODS: Changes in the best-corrected visual acuity and the subfoveal thickness of the retina and choroid were studied in 56 consecutive eyes with polypoidal choroidal vasculopathy treated initially with a combination therapy of either intravitreal ranibizumab injection (n = 23) or intravitreal aflibercept injection (n = 33) followed by photodynamic therapy. Factors associated with visual improvement and retreatment were investigated. RESULTS: Best-corrected visual acuity significantly improved with significant reduction in central macular thickness and subfoveal choroidal thickness at all points irrespective of treatment modalities (P < 0.001). Better best-corrected visual acuity and improvement of best-corrected visual acuity at 12 months were associated with baseline greater subfoveal choroidal thickness (P = 0.028 and P = 0.028) and baseline smaller greatest linear dimension (P = 0.0077 and P = 0.0077). Retreatment during 12-month follow-up was associated with baseline lesser subfoveal choroidal thickness (P = 0.036). CONCLUSION: Irrespective of treatment modalities, the visual outcome at 12 months is favorable in eyes with polypoidal choroidal vasculopathy treated by photodynamic therapy combined with intravitreal ranibizumab or aflibercept. Baseline greater subfoveal choroidal thickness was associated with a better visual outcome and with reduction in the need for retreatment.

Retreatment of polypoidal choroidal vasculopathy after photodynamic therapy combined with intravitreal ranibizumab.

PURPOSE: To investigate the incidence, risk factors and effect on visual improvement of retreatment within 60 months after initial photodynamic therapy (PDT) combined with intravitreal ranibizumab (IVR) in eyes with treatment-naïve polypoidal choroidal vasculopathy (PCV). METHODS: We retrospectively reviewed the medical records of 61 eyes from 60 patients with PCV, who were followed up for at least 12 months after undergoing combination therapy. Retreatment, including combination therapy or IVR alone, was administered if residual or recurrent exudative changes were present. RESULTS: During the follow-up period (mean 44 ± 13 months, median 48 months), 46 eyes (75.4 %) underwent retreatment. Survival analysis revealed that the proportions of eyes that were retreatment-free were 59 % at the 12-month visit, 41 % at the 24 month, 31 % at the 36 month, and 20 % at the 60-month visit. The median retreatment-free period was 15.0 [95 % confidence interval (CI) 7.4-22.7] months, and the mean period was 24.9 (95 % CI 19.3-30.6) months. Cox regression analysis revealed that older age (P = 0.010, hazard ratio 1.06, CI 1.02-1.11) and male gender (P = 0.043, hazard ratio 2.41, CI 1.03-5.62) were associated with retreatment. Visual improvement was significantly better in eyes without retreatment compared with those with retreatment at the 12-, 24- and 48-month visits. CONCLUSIONS: About 80 % of eyes with PCV require retreatment within 5 years after combination therapy with PDT and IVR. Retreatment is associated with older age and male gender and is related to reduced improvement of visual acuity.

Comparison of initial treatment between 3-monthly intravitreal aflibercept monotherapy and combined photodynamic therapy with single intravitreal aflibercept for polypoidal choroidal vasculopathy.

PURPOSE: To compare the efficacy of two different initial treatment modalities on visual outcome, need for retreatment, and angiographic improvement during 12-month follow-up for polypoidal choroidal vasculopathy (PCV). METHODS: A retrospective medical chart review was performed for 66 eyes from 66 patients with treatment-naïve PCV. Visual and angiographic improvements and the incidence of retreatment for recurrence or residual pathology were compared between two groups that underwent either intravitreal aflibercept injection (IAI) monotherapy (n = 33) or combined photodynamic therapy (PDT) with IAI (n = 33). RESULTS: Best-corrected visual acuity improved significantly (P < 0.001) in both groups at each of the 3-monthly visits during the 12-month follow-up period, with no difference between groups at 12 months (P = 0.56). The relative risk of the need for retreatment was significantly lower in the combined PDT and IAI group than in the IAI monotherapy group (P = 0.007). Angiographic regression of polypoidal vascular lesions occurred more frequently in the combined PDT group than in the IAI monotherapy group at 3 (87.5 % vs 56.7 %) and 12 months (68.8 % vs 60.0 %) (p = 0.0065 and p = 0.47 respectively). CONCLUSIONS: The combination of PDT with IAI as the initial treatment for PCV may be superior to IAI monotherapy in terms of disease-stabilizing efficacy, but with equivalent visual gain at 12 months.

Factors Predictive of Visual Outcome 1 Year After Intravitreal Aflibercept Injection for Typical Neovascular Age-Related Macular Degeneration.

PURPOSE: Several factors have been reported to be associated with visual outcomes after intravitreal ranibizumab treatment for neovascular age-related macular degeneration (AMD). In the present study, we investigated the factors associated with visual outcomes after intravitreal aflibercept injection (IAI) for typical neovascular AMD. METHODS: We retrospectively studied the visual changes in 47 eyes of 51 patients with typical neovascular AMD, who had been initially treated with 3 monthly IAI followed by as-needed IAI. RESULTS: Mean best-corrected visual acuity (BCVA) improved during the 12-month follow-up period in 40 eyes of 37 patients without reticular pseudodrusen (RPD) in both eyes, whereas it deteriorated in 11 eyes of 10 patients with RPD in either eye. Multiple regression analysis revealed that visual gain at 12 months after the first IAI positively correlated with worse baseline BCVA and thicker baseline subfoveal choroidal thickness (P = 0.018, P = 0.004, respectively), but not with absence of RPD (P = 0.13). Subfoveal choroidal thickness was significantly thinner in eyes with RPD compared with that in eyes without RPD (P = 0.003). CONCLUSIONS: Visual gain after IAI in eyes with typical neovascular AMD appears to be limited in patients with RPD, which may reflect the poor visual outcome after IAI in eyes with a thinner subfoveal choroid that is seen predominately in patients with RPD.

Prevalence and Genetic Characteristics of Geographic Atrophy among Elderly Japanese with Age-Related Macular Degeneration.

OBJECTIVE: To investigate the prevalence and genetic characteristics of geographic atrophy (GA) among elderly Japanese with advanced age-related macular degeneration (AMD) in a clinic-based study. METHODS: Two-hundred and ninety consecutive patients with advanced AMD were classified into typical neovascular AMD, polypoidal choroidal vasculopathy (PCV), retinal angiomatous proliferation (RAP) or geographic atrophy (GA). Genetic variants of ARMS2 A69S (rs10490924) and CFH I62V (rs800292) were genotyped using TaqMan Genotyping Assays. The clinical and genetic characteristics were compared between patients with and without GA. RESULTS: The number of patients diagnosed as having typical neovascular AMD, PCV, RAP and GA were 98 (33.8%), 151 (52.1%), 22 (7.5%) and 19 (6.6%), respectively. Of 19 patients with GA, 13 patients (68.4%) had unilateral GA with exudative AMD in the contralateral eye. Patients with GA were significantly older, with a higher prevalence of reticular pseudodrusen, bilateral involvement of advanced AMD and T-allele frequency of ARMS2 A69S compared with those with typical AMD and PCV; although there were no differences in the genetic and clinical characteristics among patients with GA and RAP. CONCLUSIONS: The prevalence of GA was 6.6% among elderly Japanese with AMD. Patients with GA and RAP exhibited genetic and clinical similarities.

GENETIC FACTORS ASSOCIATED WITH CHOROIDAL VASCULAR HYPERPERMEABILITY AND SUBFOVEAL CHOROIDAL THICKNESS IN POLYPOIDAL CHOROIDAL VASCULOPATHY.

PURPOSE: To investigate genetic factors associated with choroidal vascular hyperpermeability (CVH) and subfoveal choroidal thickness in eyes with treatment-naive polypoidal choroidal vasculopathy. METHODS: We studied 149 consecutive patients with polypoidal choroidal vasculopathy. The presence of CVH was evaluated using indocyanine green angiography. Subfoveal choroidal thickness and axial length were measured by spectral domain optical coherence tomography and optical biometry, respectively. Genotyping of three single nubleotide polymorphisms (SNPs), including age-related maculopathy susceptibility 2 (ARMS2) A69S (rs10490924), complement factor H (CFH) I62V (rs800292), and CFH (rs1329428), which are reportedly associated with central serous chorioretinopathy, was conducted using TaqMan technology. RESULTS: Thicker subfoveal choroidal thickness was associated with younger age, shorter axial length, G-allele frequency in ARMS2 A69S (rs10490924), and T-allele frequency in CFH (rs1329428) (P = 0.001, P < 0.001, P = 0.004, and P = 0.002, respectively; multiple regression analysis). Among 149 eyes with polypoidal choroidal vasculopathy, 35 eyes (23.5%) exhibited CVH on indocyanine green angiography. Patients with CVH had a significantly higher frequency of the G allele of ARMS2 A69S (rs10490924) and the T allele of CFH (rs1329428), which are reported to be risk alleles for central serous chorioretinopathy (P = 0.006 and P = 0.032, respectively; multivariate regression analysis). CONCLUSION: Subfoveal choroidal thickness and CVH in eyes with treatment-naive polypoidal choroidal vasculopathy were associated with ARMS2 A69S (rs10490924) and CFH (rs1329428).

Risk Factors for Second Eye Involvement in Eyes with Unilateral Polypoidal Choroidal Vasculopathy.

PURPOSE: To investigate risk factors associated with developing polypoidal choroidal vasculopathy (PCV) lesions in the unaffected fellow eye of patients with unilateral PCV. METHODS: We studied 179 patients with initial unilateral PCV who were followed up for a period of 24 months or longer to monitor for second eye involvement. All patients underwent genotyping for CFH I62V (rs800292) and ARMS2 A69S (rs10490924) using TaqMan technology. RESULTS: During the follow-up period ranging from 5-180 months, 20 (11.2%) of 179 patients developed PCV in the initially unaffected fellow eye. The risk allele (T) of ARMS2 A69S was significantly more prevalent in patients with second eye involvement compared to those without PCV in the fellow eye (p = 0.0046). Cox regression analysis demonstrated that the ARMS2 A69S genotype is a risk factor for developing PCV in the fellow eye (p = 0.027, odds ratio 2.53, confidence interval 1.11-5.73). Survival analysis revealed that the fellow eye of patients with the risk-associated homozygous genotype (TT) of ARMS2 A69S was affected significantly earlier than those with other genotypes (p = 0.0177, log rank test). CONCLUSIONS: Development of PCV in the unaffected fellow eye is associated with ARMS2 A69S genotype in patients with unilateral PCV.

Comparison of a remote operating slit-lamp microscope system with a conventional slit-lamp microscope system for examination of trabeculectomy eyes.

PURPOSE: To compare 2-dimensional (2D) photo imaging with slit-lamp photo imaging for examination of trabeculectomy eyes, and to compare the accuracy and consistency of examination of trabeculectomy eyes with a remote operating slit-lamp microscope system (referred to as "remote slit lamp" hereafter) and a conventional slit-lamp microscope system (referred to as "slit lamp" hereafter). METHODS: Thirty-five eyes of 35 patients having a history of trabeculectomy were enrolled in the study that compared 2D photo imaging with slit-lamp photo imaging for the evaluation of trabeculectomy eyes. Five ophthalmologists evaluated the 2D images and the slit-lamp images independently with masking of patient information. Evaluation scores were compared with those provided by a glaucoma specialist using the slit lamp as standard. Fifteen eyes from 15 patients having a history of trabeculectomy were enrolled in the study that investigated the accuracy and consistency of examination of trabeculectomy eyes with a remote slit lamp and a slit lamp. RESULTS: Central anterior chamber depth, bleb height, and bleb extent evaluated by the slit-lamp photo imaging showed significantly higher consistency with the standard than those evaluated by 2D photo imaging (P<0.05). The remote slit lamp showed good consistency of all the evaluated parameters with the slit lamp and the κ scores of all the evaluated parameters were higher than 0.8. The completion time for evaluation with the remote slit lamp and the slit lamp were 247.3±153.5 and 123.5±53.7 seconds, respectively (P<0.001). CONCLUSIONS: Slit-lamp photo imaging is a superior method for examination of trabeculectomy eyes compared with 2D photo imaging. The remote slit-lamp system shows similar potential to the slit-lamp system for the evaluation of trabeculectomy eyes, although the evaluation time is much longer.

Role of complement factor H I62V and age-related maculopathy susceptibility 2 A69S variants in the clinical expression of polypoidal choroidal vasculopathy.

PURPOSE: To investigate the role of complement factor H (CFH) I62V (rs800292) and age-related maculopathy susceptibility 2 (ARMS2) A69S (rs10490924) variants in the clinical characteristics of polypoidal choroidal vasculopathy (PCV). DESIGN: Cross-sectional study. PARTICIPANTS: A total of 226 Japanese patients with PCV in both eyes (44 cases) or in 1 eye (182 cases). METHODS: Genotyping was performed in all cases for CFH I62V using TaqMan technology and for ARMS2 A69S by denaturing high-performance chromatography. The incidence of 5 characteristic funduscopic findings was studied, including serous retinal detachment, subretinal hemorrhage, serous pigment epithelial detachment (PED), hemorrhagic PED, and classic choroidal neovascularization (CNV). MAIN OUTCOME MEASURES: The association of clinical phenotypes, including the incidence of each of 5 specific fundus findings, bilaterality of the disease, and age at onset, with variants of CFH I62V or ARMS2 A69S. RESULTS: Although there was no association of CFH I62V variants with any of the phenotypes in PCV, at-risk variants of ARMS2 A69S were associated with higher incidences of subretinal hemorrhage, serous PED, and hemorrhagic PED. In particular, the at-risk allele homozygosity of ARMS2 A69S increased the likelihood for hemorrhagic PED by 12.4-fold compared with non-carriers of the allele (confidence interval, 1.60-95.1, P = 0.0001). However, the at-risk allele of ARMS2 A69S was associated with a lower incidence of serous retinal detachment (P = 0.0092). Classic CNV was not associated with either variant. The mean age at the onset of PCV was significantly younger (68.8 years) in those with homozygosity of the at-risk allele of ARMS2 A69S than in those with heterozygosity (71.6 years) or in non-carriers (72.6 years) (P = 0.026). Moreover, the at-risk allele frequencies of the ARMS2 A69S were significantly higher in bilateral cases than in unilateral cases (75.0% vs. 59.3%, P = 0.007). CONCLUSIONS: ARMS2 A69S variants were significantly associated with hemorrhagic or subpigment epithelium lesions of PCV, and with earlier onset and bilateral involvement. The genotyping of ARMS2 A69S is more informative than that of CFH I62V in understanding the clinical features in patients with PCV.

Association of LOC387715 A69S genotype with visual prognosis after photodynamic therapy for polypoidal choroidal vasculopathy.

PURPOSE: To investigate whether there is an association of the LOC387715 A69S genotype with visual prognosis after photodynamic therapy in eyes with polypoidal choroidal vasculopathy (PCV). METHODS: Photodynamic therapy was repeated every 3 months until the disappearance of angiographic signs of active lesions in 71 eyes of 71 patients with PCV who were followed-up for at least 12 months. All patients were genotyped for LOC387715 A69S polymorphism (rs10490924, risk-allele T). RESULTS: Although there was no statistically significant difference in the mean baseline visual acuity (P = 0.53) among the 3 genotypes, there was a statistically significant difference in the visual acuity both at the 12-month and final visits (P = 0.002 and P < 0.001, respectively) with the poorer acuity in patients with the higher "T-"allele frequency. "T" allele was more frequently observed in those with the recurred PCV lesions (odds ratio: 5.8, 95% confidential interval: 2.3-15.1, T vs. G). CONCLUSION: There is a pharmacogenetic association between the LOC387715 A69S variant and the long-term results after photodynamic therapy in eyes with PCV. The LOC387715 A69S genotype is of clinical importance to predict the visual prognosis after photodynamic therapy in eyes with PCV. These results should be confirmed or refuted by replication studies.

Angiographic lesion size associated with LOC387715 A69S genotype in subfoveal polypoidal choroidal vasculopathy.

PURPOSE: To investigate whether the LOC387715/ARMS2 variants are associated with an angiographic phenotype, including lesion size and composition, in subfoveal polypoidal choroidal vasculopathy. METHODS: Ninety-two subjects with symptomatic subfoveal polypoidal choroidal vasculopathy, whose visual acuity was from 0.1 to 0.5 on the Landolt chart, were genotyped for the LOC387715 polymorphism (rs10490924) using denaturing high-performance chromatography. The angiographic phenotype, including lesion composition and size, was evaluated by evaluators who were masked for the genotype. Lesion size was assessed by the greatest linear dimension based on fluorescein or indocyanine green angiography. RESULTS: Although there was no statistically significant difference in lesion size on indocyanine green angiography (P = 0.36, Kruskal-Wallis test) and in lesion composition (P = 0.59, chi-square test) among the 3 genotypes, there was a statistically significant difference in lesion size on fluorescein angiography (P = 0.0022, Kruskal-Wallis test). CONCLUSION: The LOC387715 A69S genotype is not associated with lesion composition or size on indocyanine green angiography but with lesion size on fluorescein angiography in patients with subfoveal polypoidal choroidal vasculopathy. Because fluorescein angiography findings represent secondary exudative changes, including subretinal hemorrhages and retinal pigment epithelial detachment, the results in the present study likely indicate that the T allele at the LOC387715 gene is associated with the exudative activity of polypoidal lesions.