INCIDENCE AND CHARACTERISTICS OF NEOVASCULAR AGE-RELATED MACULAR WITH OVER A 12-MONTH REMISSION AFTER THREE MONTHLY AFLIBERCEPT ADMINISTRATION: 60 Months Results of a Pro Re Nata Regimen.

PURPOSE: To investigate the characteristics of patients with over a 12-month remission after 3 monthly intravitreal aflibercept injections followed by a pro re nata regimen for exudative age-related macular degeneration (AMD). METHODS: One hundred forty-four eyes with exudative AMD were included. All patients received 3 monthly intravitreal aflibercept injections as a loading dose, followed by an as-needed regimen for 60 months. Patients were classified into the remission and recurrence groups depending on the presence or absence of a 12-month remission. ARMS2 A69S and CFH I62V were genotyped in all cases. RESULTS: During the study, 82 eyes (56.9%) showed 12 months or more remission at least once. The cumulative incidence rate of a 12-month remission showed a plateau pattern and converged to 60% (y = -166.26x-2.172 + 0.6, R2 = 0.8168). Patients in the remission group were younger than those in the recurrence group (P < 0.001) and had less risk allele frequency of the ARMS2 gene than the recurrence group (P < 0.001). The longer the remission interval was prolonged, the better visual acuity was achieved at the 60-month visit (P < 0.001). CONCLUSION: Fifty-seven percent of patients showed a 12-month remission or more at least once during a 60-month follow-up, suggesting that patients with no reactivation can prolong the treatment interval.

DISTINCT CHARACTERISTICS OF SIMPLE VERSUS COMPLEX CENTRAL SEROUS CHORIORETINOPATHY.

PURPOSE: To compare the clinical and genetic characteristics of simple and complex central serous chorioretinopathy using central serous chorioretinopathy international group criteria. METHODS: Patients with idiopathic central serous chorioretinopathy were included. Depending on the presence or absence of retinal pigment alterations greater than 2-disc areas in either eye, patients were classified into complex or simple types. Demographic factors and clinical findings were compared between groups. CFH variants, including rs800292 and rs1329428, were genotyped using TaqMan technology. RESULTS: A total of 319 consecutive patients were evaluated at the initial presentation. Of them, 53 (16.6%) had the complex type. The complex type was exclusively seen in men (100% vs. 79.0%, P = 2.0 × 10 -4 ) and demonstrated a significantly higher proportion of bilateral involvement (75.5% vs. 17.7%, P = 6.2 × 10 -18 ) and descending tract(s) (83.0% vs. 0%, P = 1.2 × 10 -57 ) than the simple type. Increased choroidal thickness (425 ± 131 vs. 382 ± 110, P = 0.02) and decreased central retinal thickness (274 ± 151 vs. 337 ± 136, P = 2.9 × 10 -4 ) were observed for the complex versus simple type. The risk allele frequencies of both variants were significantly higher in the complex versus simple type (rs800292: 61.3% vs. 48.7%, P = 0.018; rs1329428: 65.1% vs. 54.3%, P = 0.04). CONCLUSION: In this new classification system, the complex type has distinct genetic and clinical characteristics compared with the simple type.

CFH and VIPR2 as susceptibility loci in choroidal thickness and pachychoroid disease central serous chorioretinopathy.

Central serous chorioretinopathy (CSC) is a common disease affecting younger people and may lead to vision loss. CSC shares phenotypic overlap with age-related macular degeneration (AMD). As recent studies have revealed a characteristic increase of choroidal thickness in CSC, we conducted a genome-wide association study on choroidal thickness in 3,418 individuals followed by TaqMan assays in 2,692 subjects, and we identified two susceptibility loci: CFH rs800292, an established AMD susceptibility polymorphism, and VIPR2 rs3793217 (P = 2.05 × 10-10 and 6.75 × 10-8, respectively). Case-control studies using patients with CSC confirmed associations between both polymorphisms and CSC (P = 5.27 × 10-5 and 5.14 × 10-5, respectively). The CFH rs800292 G allele is reportedly a risk allele for AMD, whereas the A allele conferred risk for thicker choroid and CSC development. This study not only shows that susceptibility genes for CSC could be discovered using choroidal thickness as a defining variable but also, deepens the understanding of differences between CSC and AMD pathophysiology.

Drusenoid Pigment Epithelial Detachment: Genetic and Clinical Characteristics.

Few studies report drusenoid pigment epithelial detachment (DPED) in Asians. In this multicenter study, we report the clinical and genetic characteristics of 76 patients with DPED, and, for comparison, 861 patients with exudative age-related macular degeneration (AMD) were included. On the initial presentation, the mean best-corrected visual acuity was 0.087 ± 0.17 (logMAR unit), and mean DPED height and width were 210 ± 132 and 1633 ± 1114 µm, respectively. Fifty-one (67%) patients showed macular neovascularization in the contralateral eye. The risk allele frequency of both ARMS2 A69S and CFH I62V was significantly higher in DPED than in typical AMD and polypoidal choroidal vasculopathy (PCV) (ARMS2 A69S risk allele frequency: DPED 77% vs. typical AMD 66% vs. PCV 57%, CFH I62V risk allele frequency: DPED 87% vs. typical AMD 73% vs. PCV 73%), although the risk allele frequency of both genes was similar between the DPED group and retinal angiomatous proliferation (RAP) group (ARMS2 A69S: p = 0.32, CFH I62V, p = 0.11). The prevalence of reticular pseudodrusen (RPD) was highest in RAP (60%), followed by DPED (22%), typical AMD (20%), and PCV (2%). Although the prevalence of RPD differs between DPED and RAP, these entities share a similar genetic background in terms of ARMS2 and CFH genes.

Focal Scleral Nodule: A New Name for Solitary Idiopathic Choroiditis and Unifocal Helioid Choroiditis.

PURPOSE: To evaluate multimodal imaging findings of solitary idiopathic choroiditis (SIC; also known as unifocal helioid choroiditis) to clarify its origin, anatomic location, and natural course. DESIGN: Multicenter retrospective observational case series. PARTICIPANTS: Sixty-three patients with SIC in 1 eye. METHODS: Demographic and clinical data were collected. Multimodal imaging included color fundus photography, OCT (including swept-source OCT), OCT angiography (OCTA), fundus autofluorescence, fluorescein and indocyanine green angiography, and B-scan ultrasonography. MAIN OUTCOME MEASURES: Standardized grading of imaging features. RESULTS: Mean age at presentation was 56 ± 15 years (range, 12-83 years). Mean follow-up duration in 39 patients was 39 ± 55 months (range, 1 month-25 years). The lesions measured a mean of 2.4 × 2.1 mm in basal diameter, were located inferior (64%) or nasal to the optic disc, and appeared yellow (53%). No systemic associations were found. The lesions all appeared as an elevated subretinal mass, with OCT demonstrating all lesions to be confined to the sclera, not the choroid. On OCT, the deep lesion margin was visible in 12 eyes with a mean lesion thickness of 0.6 mm. Overlying choroidal thinning or absence was seen in 95% (mean choroidal thickness, 28 ± 35 µm). Mild subretinal fluid was observed overlying the lesions in 9 patients (14%). Retinal pigment epithelial disruption and overlying retinal thinning was observed in 56% and 57%, respectively. OCT angiography was performed in 13 eyes and demonstrated associated choroidal and lesional flow voids. Four lesions (6%) were identified at the macula, leading to visual loss in 1 patient. One lesion demonstrated growth and another lesion showed spontaneous resolution. CONCLUSIONS: In this largest series to date, multimodal imaging of SIC demonstrated a scleral location in all patients. The yellow and white clinical appearance may be related to scleral unmasking resulting from atrophy of overlying tissues. Additional associated features included documentation of deep margin on swept-source OCT, trace subretinal fluid in a few patients, and OCTA evidence of lesional flow voids. Because of the scleral location of this lesion in every patient, a new name, focal scleral nodule, is proposed.

RELATIONSHIP BETWEEN CHOROIDAL VASCULAR HYPERPERMEABILITY, CHORIOCAPILLARIS FLOW DENSITY, AND CHOROIDAL THICKNESS IN EYES WITH PACHYCHOROID PIGMENT EPITHELIOPATHY.

PURPOSE: To use swept-source optical coherence tomography and swept-source optical coherence tomography angiography to investigate potential relationships between choroidal vascular hyperpermeability (CVH) seen with indocyanine green angiography (ICGA), choriocapillaris flow density, and choroidal thickness in eyes with pachychoroid pigment epitheliopathy. METHODS: Patients with pachychoroid pigment epitheliopathy were prospectively imaged with 12-mm × 12-mm swept-source optical coherence tomography, 12-mm × 12-mm swept-source optical coherence tomography angiographyA, and ICGA. Binarized choriocapillaris OCTA images were superimposed with ICGA images in which CVH area had been isolated. Choriocapillaris flow density within or outside the quadrants of CVH was calculated and the ratio of these two values was determined. The presence of CVH and choroidal thickness was evaluated at 9 locations within a central 3-mm × 3-mm area to explore the relationship between these 2 factors. RESULTS: Ten eyes from 10 patients were enrolled in the present study. Choriocapillaris flow density within quadrants of CVH area was significantly lower compared with quadrants without CVH (P < 0.001). The mean choriocapillaris flow density ratio was 0.86 ± 0.10 (range: 0.65-0.99). From among the 90 locations in 10 study eyes, 48 were within areas of CVH. Choroidal thickness was greater in quadrants of CVH compared with areas without CVH (P < 0.001, 455 ± 122 µm vs. 297 ± 93 µm). CONCLUSION: Reduced choriocapillaris flow density, increased choroidal thickness, and CVH appear to co-localize in eyes with pachychoroid pigment epitheliopathy.

CUTICULAR DRUSEN: Risk of Geographic Atrophy and Macular Neovascularization.

PURPOSE: Cuticular drusen (CD) have been associated with manifestations of age-related macular degeneration such as atrophy and neovascularization in the macula. In this study, eyes with CD were followed and investigated for the estimated 5-year risk of progression to sequelae of age-related macular degeneration such as geographic atrophy (GA) and macular neovascularization (MNV). METHODS: A consecutive series of patients with CD were followed for the development of GA and MNV. Whenever possible, they were also studied retrospectively. The patients with CD were categorized into three phenotypic groups. Phenotype 1: eyes had concentrated, densely populated CD in the macular and paramacular area, Phenotype 2: eyes showed scattered CD in the posterior fundus, and Phenotype 3: involved eyes with CD mixed with large drusen (>200 µm). The 5-year incidence of progression was then estimated using a Kaplan-Meier estimator. RESULTS: A total of 63 eyes from 38 patients (35 women with a mean age at presentation of 58.9 ± 14.2 years) were studied and followed for a mean of 40 ± 18 months. Thirteen patients had single eyes with GA (84.5%; 11/13) or MNV (15.5%; 2/13) in one eye at presentation and were subsequently excluded. Geographic atrophy developed in 19.0% (12/63) of eyes and MNV in 4.8% (3/63) of eyes. The cumulative estimated 5-year risk of GA and MNV was 28.4% and 8.7%, respectively. The estimated 5-year incidence of MNV or GA was 12.6%, 50.0%, and 51.6% in Phenotype 1, Phenotype 2, and Phenotype 3, respectively (P = 0.0015, log-rank test). No difference in risk was found in the development of GA or MNV (P = 0.11) between the subgroup of patients presenting with GA or MNV in their fellow eye and those with both eyes included. CONCLUSION: When patients with CD are followed longitudinally, there was a significant risk of progression to GA or MNV for Phenotype 2 and Phenotype 3. Patients with CD are commonly first diagnosed in the fifth decade of life, and there is a female predominance. Clinicians should use multimodal imaging to detect and be aware of the risk of progression to manifestations of GA and MNV. These risks of GA and MNV suggest that patients with CD may be part of the overall spectrum of age-related macular degeneration.

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.

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.

ASSOCIATION BETWEEN CHOROIDAL CAVERNS AND CHOROIDAL VASCULAR HYPERPERMEABILITY IN EYES WITH PACHYCHOROID DISEASES.

PURPOSE: To investigate the association between choroidal caverns, choroidal vascular hyperpermeability (CVH), and pachyvessels in eyes with pachychoroid disease. METHODS: This was a retrospective review of swept-source optical coherence tomography and indocyanine green angiography imaging performed on eyes with pachychoroid disease. RESULTS: Imaging from 21 eyes with pachychoroid disease entities (8 eyes with pachychoroid pigment epitheliopathy, 11 eyes with central serous chorioretinopathy, and 3 eyes with pachychoroid neovasculopathy) from 11 patients (mean 49.5 years, male/female: 10/1, all white) was available for review. In all study eyes, pachyvessels traversed the areas of CVH visible in mid- and late-phase indocyanine green angiography. A total of 504 choroidal caverns were identified in 11 study eyes (52%). Of the 504 choroidal caverns, 445 (88%) were seen within the areas of CVH compared with 59 (12%), which were detected outside the areas of CVH (P < 0.001). Eyes with multiple caverns had an increased choroidal thickness when compared with eyes with ≤1 cavern (P < 0.001). CONCLUSION: Choroidal caverns, found primarily in the areas of indocyanine green angiography CVH traversed by pachyvessels, were detected in 52% of eyes with pachychoroid disease. The presence of choroidal caverns in these cases may indicate a loss of normal choroidal architecture associated with dilated Haller layer veins and increased choroidal thickness.

Retreatment of Exudative Age-Related Macular Degeneration after Loading 3-Monthly Intravitreal Ranibizumab.

PURPOSE: The aim of this study was to investigate the clinical implications of required retreatment after 3-monthly intravitreal ranibizumab (IVR) injections followed by as-needed reinjections up to 5 years in eyes with exudative age-related macular degeneration (AMD). METHODS: A retrospective cohort study was conducted for 165 treatment-naïve eyes from 165 patients with exudative AMD. Visual changes were investigated in terms of the required retreatments. RESULTS: Retreatment-free proportions were 37.0, 23.7, 16.6, 12.1, and 10.5% at 12, 24, 36, 48, and 60 months, respectively. Visual changes were significantly better in eyes which did not require retreatment at every yearly checkpoint within the 5 years. A multivariate logistic regression analysis revealed that requirement of additional IVR treatments in the first 12-24 months was associated with the T allele (risk allele) of ARMS2 A69S (p = 0.010 and 0.015, respectively). Cox regression analysis revealed that older age (p = 0.046) and the T allele of ARMS2 A69S (p = 0.036) were associated with required retreatment within the 5-year follow-up period. CONCLUSIONS: Age and the T allele of ARMS2 A69S are the risk factors requiring retreatments, leading to poor visual change in eyes with exudative AMD following the initial 3-monthly IVR.

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.

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.

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.

Treatment Patterns and Health Care Costs for Age-Related Macular Degeneration in Japan: An Analysis of National Insurance Claims Data.

PURPOSE: To investigate changes in the proportion of patients with age-related macular degeneration (AMD) visiting hospitals and to investigate factors associated with AMD, treatments, and medical expenses, as well as the outlook for AMD in Japan using a large health insurance database. DESIGN: Analysis of national insurance claims data. PARTICIPANTS: People 40 years of age or older who were registered in the Japan Medical Data Center database. METHODS: Patients with AMD were identified from 2005 through 2013 based on International Classification of Diseases, 10th revision, diagnosis codes. Changes in patient proportions, treatment procedures, and medical expenses were investigated during the study period. The data for each year were compared after adjustment based on the 2010 Japanese population annual census. The outlook for patients with AMD was predicted based on the combination of data in 2013 and an official future population prediction report. MAIN OUTCOME MEASURES: Changes in treatment patterns and health care costs in Japan. RESULTS: A total of 3 401 299 participants were included in the analysis, and 3058 AMD patients were identified over the 9-year period. The proportion of patients with AMD increased significantly from 0.084% (95% confidence interval, 0.050%-0.119%) in 2005 to 0.26% (95% confidence interval, 0.24%-0.29%) in 2013 (P = 0.0001, Pearson correlation coefficient test). There were significantly more men than women (odds ratio, 1.25; 95% confidence interval, 1.14-1.37), and the proportion of patients with AMD increased rapidly with age. Photodynamic therapy was replaced by anti-vascular endothelial growth factor (VEGF) therapy as the predominant therapy from 2009 onward. Medical expenses per 10 000 persons increased from $1530 to $137 000 over the 9-year period. The proportion of AMD patients is predicted to increase in the future and will reach a maximum of 223 000 in 2035. CONCLUSIONS: The proportion of AMD patients visiting hospitals, medical expenses, and the frequency of anti-VEGF therapy increased significantly over the 9-year period. These increasing trends are predicted to continue in Japan.

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).

Aqueous humor cytokine levels in patients with polypoidal choroidal vasculopathy and neovascular age-related macular degeneration.

PURPOSE: To investigate the possible roles of various cytokines or growth factors in the pathogenesis of exudative age-related macular degeneration (AMD) by comparing aqueous humor levels of 14 cytokines between eyes with polypoidal choroidal vasculopathy (PCV) and those with neovascular AMD. METHODS: Forty eyes from 40 patients with treatment-naïve exudative AMD consisting of 18 eyes with neovascular AMD and 22 eyes with PCV were studied. Twenty eyes from 20 patients with no retinal pathology who underwent cataract surgery served as controls. Aqueous humor samples were collected just before intravitreal ranibizumab injection in 40 eyes with exudative AMD and before cataract surgery in 20 control eyes. Concentrations of 14 cytokines were determined by chemiluminescence-based ELISA: interleukin (IL)-1α, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12, IL-13, IL-15, IL-17, vascular endothelial growth factor (VEGF), monocyte chemoattractant protein 1, interferon-γ-inducible protein (IP)-10 and C-reactive protein (CRP). RESULTS: After adjusting for gender, age and axial length, concentrations of CRP and IP-10 were significantly higher in eyes with neovascular AMD or PCV compared with control eyes (p < 0.05), and IP-10 levels were strongly associated with lesion size (p = 0.002). None of the 14 cytokines, including VEGF, were significantly different between eyes with neovascular AMD and those with PCV. CONCLUSION: Aqueous humor concentrations of CRP and IP-10 were elevated in eyes with PCV or neovascular AMD. IP-10 could be associated with the pathogenesis of neovascular AMD and PCV.

Genetic and clinical factors associated with reticular pseudodrusen in exudative age-related macular degeneration.

BACKGROUNDS: Reticular pseudodrusen (RPD) is considered to be a distinct entity from soft drusen and a risk factor for age-related macular degeneration (AMD). In the present study, we investigate the genetic and clinical factors associated with reticular pseudodrusen (RPD) in patients with exudative AMD, including polypoidal choroidal vasculopathy (PCV), typical neovascular AMD, and retinal angiomatous proliferation (RAP). METHODS: The presence or absence of RPD was studied among 408 patients with exudative AMD in at least one eye, and the clinical characteristics of those with RPD were investigated as well as genetic polymorphisms of ARMS2 A69S (rs10490924) and CFH I62V (rs800292). Subfoveal choroidal thickness was also evaluated in a limited number of subjects using the EDI mode of spectral-domain optical coherence tomography. RESULTS: The prevalence of RPD was significantly higher in RAP eyes than in typical neovascular AMD or in PCV eyes (38.2% of 26 eyes, 13.6% of 132 eyes and 0% of 250 eyes respectively, P < 0.0001). RPD was significantly more prevalent in the elderly (P < 0.0001) and female (P < 0.0001) subjects. The subfoveal choroidal thickness was thinner in eyes with RPD than in those without (129.7 ± 61.7 µm vs 42.6 ± 84.9 µm, P < 0.0001). The frequency of risk variants of ARMS2 A69S was significantly higher in eyes with RPD than in those without RPD (85.7% vs 63.8%, P = 0.0009), although the frequency of CFH I62V was not significantly different between those with and without RPD. Logistic regression analysis revealed that age (odds ratio [OR]:1.10; 95% confidence interval [CI]: 1.04-1.18; p = 0.002), female gender (OR:4.26; 95%CI: 1.72-10.4; p = 0.002), T-allele at ARMS2 A69S (OR: 3.23; 95%CI: 1.36-7.68; p = 0.008) and RAP (OR: 4.25; 95%CI:1.49-12.1; p = 0.007) were risk factors for RPD. CONCLUSIONS: Among eyes with exudative AMD, RPD is more common in eyes with RAP having a thin choroid at the fovea, especially in old, female patients with the risk variant of ARMS2 A69S.

Association of Polyp Regression after Loading Phase with 12-Month Outcomes of Eyes with Polypoidal Choroidal Vasculopathy.

PURPOSE: We compared 12-month outcomes of eyes with polypoidal choroidal vasculopathy (PCV) with or without complete regression of polyps observed one month after three monthly intravitreal administrations (loading phase) of aflibercept (2.0 mg/0.05 mL) or brolucizumab (6.0 mg/0.05 mL). METHODS: All patients underwent indocyanine green angiography at both baseline and 3 months after initial injection and were followed up monthly with an as-needed regimen for up to 12 months. A total of 62 patients with PCV were included: 30 eyes were treated with brolucizumab, and 32 were treated with aflibercept. Eyes with complete regression of polyps (regression group) had significantly smaller maximum polyp diameter and were more frequently treated with brolucizumab than those without complete regression (non-regression) group. RESULTS: Best corrected visual acuity was comparable between the two groups at 12 months. Although the 12-month retreatment-free proportion was comparable between the two groups (33.0% versus 27.0%, p = 0.59), a retreatment-free period was significantly longer in the regression group than in the non-regression group (8.3 ± 3.3 versus 6.5 ± 3.6 months, p = 0.022), and the number of additional injections was significantly fewer in the regression group than in the non-regression group (1.2 ± 1.2 versus 3.0 ± 2.6, p = 0.007). CONCLUSIONS: Complete regression of polyps observed after the initial phase possibly prolongs the retreatment-free period and reduces the number of additional injections irrespective of aflibercept or brolucizumab.