Vascular endothelial growth factor inhibitors for predominantly Caucasian myopic choroidal neovascularization: 2-year treatment outcomes in clinical practice: data from the Fight Retinal Blindness! Registry.

PURPOSE: To report the 24-month outcomes of vascular endothelial growth factor (VEGF) inhibitors for myopic choroidal neovascularization (mCNV) in predominantly Caucasian eyes in routine clinical practice. METHODS: Retrospective analysis of treatment-naïve eyes starting intravitreal injection of VEGF inhibitors of either bevacizumab (1.25 mg) or ranibizumab (0.5 mg) for mCNV from 1 January 2006 to 31 May 2018 that were tracked in the Fight Retinal Blindness! registry. RESULTS: We identified 203 eyes (bevacizumab-85 and ranibizumab-118) of 189 patients. The estimated mean (95% CI) change in VA over 24 months for all eyes using longitudinal models was +8 (5, 11) letters with a median (Q1, Q3) of 3 (2, 5) injections given mostly during the first year. The estimated mean change in VA at 24 months was similar between bevacizumab and ranibizumab [+9 (5, 13) letters for bevacizumab versus +9 (6, 13) letters for ranibizumab; p = 0.37]. Both agents were also similar in the mCNV activity outcomes, treatment frequency and visit frequency. CONCLUSIONS: The 24-month treatment outcomes of VEGF inhibitors for mCNV were favourable in this largest series yet reported of predominantly Caucasian eyes in routine clinical practice, with approximately two lines of visual gain and a median of three injections given mostly during the first year. These outcomes are similar to those reported for predominantly Asian eyes. Bevacizumab appeared to be as safe and effective as ranibizumab.

Detection of features associated with neovascular age-related macular degeneration in ethnically distinct data sets by an optical coherence tomography: trained deep learning algorithm.

BACKGROUND: The ability of deep learning (DL) algorithms to identify eyes with neovascular age-related macular degeneration (nAMD) from optical coherence tomography (OCT) scans has been previously established. We herewith evaluate the ability of a DL model, showing excellent performance on a Korean data set, to generalse onto an American data set despite ethnic differences. In addition, expert graders were surveyed to verify if the DL model was appropriately identifying lesions indicative of nAMD on the OCT scans. METHODS: Model development data set-12 247 OCT scans from South Korea; external validation data set-91 509 OCT scans from Washington, USA. In both data sets, normal eyes or eyes with nAMD were included. After internal testing, the algorithm was sent to the University of Washington, USA, for external validation. Area under the receiver operating characteristic curve (AUC) and precision-recall curve (AUPRC) were calculated. For model explanation, saliency maps were generated using Guided GradCAM. RESULTS: On external validation, AUC and AUPRC remained high at 0.952 (95% CI 0.942 to 0.962) and 0.891 (95% CI 0.875 to 0.908) at the individual level. Saliency maps showed that in normal OCT scans, the fovea was the main area of interest; in nAMD OCT scans, the appropriate pathological features were areas of model interest. Survey of 10 retina specialists confirmed this. CONCLUSION: Our DL algorithm exhibited high performance for nAMD identification in a Korean population, and generalised well to an ethnically distinct, American population. The model correctly focused on the differences within the macular area to extract features associated with nAMD.

Clinical Characteristics of Polypoidal Choroidal Vasculopathy and Anti-Vascular Endothelial Growth Factor Treatment Response in Caucasians.

BACKGROUND/AIMS: To identify the clinical characteristics of polypoidal choroidal vasculopathy (PCV) in Caucasian patients and assess the prevalence of anti-vascular endothelial growth factor (anti-VEGF) resistance. METHODS: This involved a retrospective chart review of Caucasian patients diagnosed with PCV and utilizing indocyanine green angiography with the scanning laser ophthalmoscope. Data collected included patients' demographics, disease characteristics, and treatment response. RESULTS: There were 54 eyes of 49 patients with PCV; 51.0% were male and 49.0% were female with a mean age of 72.9 years. Forty-four patients (89.8%) had PCV unilaterally and 10.2% (5 patients) had PCV bilaterally. PCV was located in the macula in 79.6%, in the peripapillary region in 16.7%, and in both regions in 3.7%. PCV commonly presents with serous detachment (66.7%), retinal pigment epithelial detachment (RPED) (51.9%) and subretinal hemorrhage (37.0%). Twenty-nine eyes were included in the treatment response analysis, with 18 eyes (62.1%) showing persistent disease activity after 3 initial injections of anti-VEGF treatment. CONCLUSION: PCV in Caucasian patients is more often unilateral and presents more commonly in the macular region than the peripapillary region. Serous detachment and RPED are the 2 most common findings. Resistance to current anti-VEGF treatment was noted frequently; it is thus extremely important to identify this subtype of type I subretinal neovascularization.

Color Fundus Photography, Optical Coherence Tomography, and Fluorescein Angiography in Diagnosing Polypoidal Choroidal Vasculopathy.

PURPOSE: To determine sensitivity and specificity of polypoidal choroidal vasculopathy (PCV) diagnosis using color fundus photography (CFP), optical coherence tomography (OCT), and fundus fluorescein angiography (FFA) without indocyanine green angiography (ICGA). DESIGN: Validity analysis. METHODS: Treatment-naïve eyes with serous/serosanguinous maculopathy undergoing CFP, OCT, FFA, and ICGA imaging before treatment at a university hospital in Thailand (January 1, 2013 to June 30, 2015) were identified. Images of each subject were categorized into 4 sets (set A: CFP; set B: CFP+OCT; set C: CFP+FFA; set D: CFP+OCT+FFA). Six graders, 3 from Thailand (PCV endemic area) and 3 from the United States (nonendemic area), individually reviewed each set (without ICGA), and determined if the presumed diagnosis was PCV. In parallel, 2 other graders confirmed if each case had PCV or not using EVEREST criteria (including ICGA). Sensitivity and specificity of a PCV diagnosis with each set (without ICGA) were analyzed compared with diagnoses including ICGA. RESULTS: Of 119 study eyes (113 subjects, 57% male, mean age ± SD 59.9 ± 13.8 years), definite PCV diagnosis was 40.3%. Sensitivity of sets A, B, C, D: 0.63 (95% confidence interval [CI]: 0.47-0.76), 0.83 (95% CI: 0.69-0.92), 0.54 (95% CI: 0.39-0.68), 0.67 (95% CI: 0.51-0.79); specificities: 0.93 (95% CI: 0.84-0.97), 0.83 (95% CI: 0.72-0.91), 0.97 (95% CI: 0.89-0.99), 0.92 (95% CI: 0.82-0.97); accuracies: 0.81 (95% CI: 0.73-0.88), 0.83 (95% CI: 0.76-0.90), 0.79 (95% CI: 0.73-0.87), 0.82 (95% CI: 0.74-0.88). Discrepancies between Thai and US graders existed through sets A, C, and D. CONCLUSIONS: These data suggest that without ICGA, fundus photography combined with OCT provides high sensitivity and high specificity to diagnose PCV; adding FFA does not improve accuracy.

Ranibizumab in Myopic Choroidal Neovascularization: A Subgroup Analysis by Ethnicity, Age, and Ocular Characteristics in RADIANCE.

PURPOSE: To assess the impact of ethnicity, age, and ocular characteristics on ranibizumab efficacy in myopic choroidal neovascularization (CNV). METHODS: In this post hoc subgroup analysis from the phase III RADIANCE study, best-corrected visual acuity (BCVA) outcomes and treatment exposure were analyzed in 105 patients treated with ranibizumab 0.5 mg. Baseline categories included ethnicity, age, baseline BCVA, lesion area, CNV lesion area, refraction sphere, axial length, subretinal fluid, and location of CNV. RESULTS: At month 12, the mean change in BCVA was numerically higher in East-Asians than in Caucasians (17.0 vs. 14.1 letters). The median number of injections varied with ethnicity (East-Asians vs. Caucasians: 2 vs. 3), baseline BCVA (highest vs. lowest: 1 vs. 4), CNV lesion area and lesion area (largest vs. smallest: 5 vs. 1 and 5 vs. 2). CONCLUSIONS: East-Asians showed numerically higher BCVA gains than Caucasians. The number of injections varied across subgroups, emphasizing the need for individualized treatment.

Clinical Characteristics of Inflammatory Choroidal Neovascularization in a Chinese Population.

PURPOSE: To describe demographic features and clinical and imaging characteristics of inflammatory choroidal neovascularization (CNV) in a Chinese population. METHODS: A retrospective case review of patients with CNV secondary to uveitis from 2002 to 2013. RESULTS: A total of 125 patients (150 eyes, 166 CNVs; bifocal CNVs in 16 eyes), 64% of whom were women, were reviewed. The mean age was 35.86 years. The proportions of patients with punctate inner choroidopathy (PIC), multifocal choroiditis (MFC), and Vogt-Koyanagi-Harada (VKH) were 50.4, 22.4, and 8%. All of the cases were classic CNV in fluorocein angiography and type 2 CNV in OCT. The proportion of subfoveal lesions in active CNV (30.09%) was less than that in inactive CNV (60.38%). CONCLUSIONS: PIC, MFC, and VKH were the three primary specific types of uveitis with inflammatory CNV in this study. Inflammatory CNV tended to break though the retinal pigment epithelium and beneath the neurosensory retina. Moreover, inflammatory CNV was usually nonsubfoveal when it occurred.

High-dose ranibizumab monotherapy for neovascular polypoidal choroidal vasculopathy in a predominantly non-Asian population.

PURPOSE: To determine safety and efficacy of intravitreal high-dose ranibizumab in the treatment of active neovascular polypoidal choroidal vasculopathy (PCV). METHODS: In this Phase I/II, single-center, randomized, controlled, double-masked study, predominantly non-Asian, previously treated or treatment-naive, male and female adult patients were randomized to receive high-dose (1.0/0.1 ml or 2.0 mg/0.05 ml; n=15) or standard-dose (0.5 mg/0.05 ml; n=5) ranibizumab in 3 monthly loading doses, followed by 9 months of criteria-based, as-needed retreatment. Safety was evaluated by a descriptive analysis of all non-serious and serious adverse events, angiographic assessments, physical examinations, vital signs, ocular examinations, and visual acuity measurements. Visual acuity and anatomic outcomes are described for the high-dose group. RESULTS: Twenty patients (aged 35-76 years; 8 Black, 11 White, 1 Asian) were enrolled. At baseline, in the high-dose group, mean best-corrected visual acuity (BCVA) was 63.5 letters (Snellen equivalent ~20/50), and mean baseline central foveal thickness (CFT) was 253.7 µm. High-dose ranibizumab was generally well tolerated without evidence of ocular or systemic severe adverse events, including arterial thromboembolic events. At month 12, in the high-dose group, the mean overall change from baseline in BCVA was +6.7 letters and in CFT was -49.7 µm. CONCLUSION: High-dose ranibizumab monotherapy is safe and efficacious for treating patients with PCV.

CHOROIDAL NEOVASCULARIZATION IN CAUCASIAN PATIENTS WITH LONGSTANDING CENTRAL SEROUS CHORIORETINOPATHY.

PURPOSE: To report the frequency of choroidal neovascularization (CNV) in Caucasian patients with chronic central serous chorioretinopathy (CSC). METHODS: Retrospective consecutive series of 272 eyes (136 patients) who were diagnosed as having chronic CSC based on clinical and multimodal fundus imaging findings and documented disease activity for at least 6 months. The CNVs were mainly determined by indocyanine-green angiography. RESULTS: Patients were evaluated and followed for a maximum of 6 years, with an average follow-up of 14 ± 12 months. Distinct CNV was identified in 41 eyes (34 patients). Based on fluorescein angiography, 37 eyes showed occult with no classic CNV, 3 eyes showed predominantly classic and 1 eye had a disciform CNV. Furthermore, indocyanine-green angiography revealed polypoidal choroidal vasculopathy lesions, in 27 of the 37 eyes, classified as occult CNV on fluorescein angiography. In total, 17.6% of our patients with chronic CSC were found to have CNV that upon indocyanine-green angiography were recognized as being polypoidal choroidal vasculopathy. CONCLUSION: In our series of Caucasian patients, we found a significant correlation between chronic CSC and CNV, in which the majority of patients with CNV were found to have polypoidal choroidal vasculopathy. Our findings suggest that indocyanine-green angiography is an indispensable tool in the investigation of chronic CSC.

The natural history of polypoidal choroidal vasculopathy: a multi-center series of untreated Asian patients.

PURPOSE: We aimed to evaluate the long-term natural history of polypoidal choroidal vasculopathy (PCV) in untreated patients. METHODS: This is a retrospective observational case series. Patients with symptomatic PCV who did not receive any treatment for at least 12 months were included from the records of three ophthalmic clinics in Asia. The medical records and imaging data were reviewed. Visual outcomes at month 12 and at last follow-up were analyzed. The influence of demographics and presenting features on visual outcome was analyzed. RESULTS: A total of 32 eyes (32 patients) were included in this analysis. The mean follow-up was 59.9 months (range, 18-119 months), the mean age was 65.7 years and 21 (65.6 %) patients were male. The mean presenting logMAR visual acuity was 0.79 (Standard deviation [SD] 0.49). The center of the fovea was involved by the PCV complex in 25 eyes (78.1 %). The mean greatest linear dimension (GLD) of the PCV complex was 2584 µm (SD 880). Twenty-three eyes (71.9 %) had a cluster-of-grapes configuration on indocyanine green angiography. Leakage of fluorescein angiography was present in 29 eyes (90.6 %). The mean logMAR vision deteriorated from 0.79 at baseline to 0.88 at month 12 (p = 0.11), and further to 1.14 (p = 0.003) at the last follow-up. The proportion of eyes that improved, remained unchanged and worsened was 21.9 %, 31.3 % and 46.9 %, respectively, at month 12; and 28.1 %, 9.4 % and 62.5 %, respectively, at last follow-up. The proportion of eyes with logMAR vision worse than 1.0 was 28.1 % at presentation, and increased to 31.3 % at month 12 and further to 53.1 % at last follow-up. Reasons for poor vision were due to retinal, subretinal or vitreous hemorrhage, and retinal pigment epithelium (RPE) atrophy and scarring. None of the presenting features were found to significantly influence visual outcome. CONCLUSIONS: Half of eyes presenting with symptomatic PCV had a relatively benign course without treatment and some even had vision improvement. However, in the remaining eyes, vision deteriorated significantly, mainly due to hemorrhage and scarring. There may be subtypes of PCV with divergent natural history.

Gender specific association of a complement component 3 polymorphism with polypoidal choroidal vasculopathy.

Neovascular age-related macular degeneration (AMD) and polypoidal choroidal vasculopathy (PCV) are leading causes of irreversible blindness in developed countries. In this study, we investigated the associations of haplotype-tagging single nucleotide polymorphisms (SNPs) in the complement component 3 (C3) gene with both neovascular AMD and PCV, and potential epistatic effects on C3. Eight tagging SNPs in C3 were genotyped in 708 unrelated study subjects: 200 neovascular AMD patients, 233 PCV patients and 275 controls. Among the eight C3 SNPs, rs17030 was associated with PCV after adjusted for gender and SNP-gender interaction (P = 0.008, OR = 2.94; 95% CI: 1.32-6.52). Moreover, an interaction between rs17030 and gender was identified in PCV (P = 0.02). After stratification by gender, the rs17030 G allele was found to confer an increased risk for PCV in male (P = 0.010, OR = 1.56) but not in female. The haplotype AG defined by the major alleles of rs17030 and rs344555 was also associated with PCV in male (P = 0.010, OR = 0.64). In contrast to PCV, none of the eight SNPs was significantly associated with neovascular AMD. This study shows an association of C3 rs17030 with PCV in male, indicating that C3 may have an epistatic effect with gender in the pathogenesis of PCV.

A prospective study of treatment patterns and 1-year outcome of Asian age-related macular degeneration and polypoidal choroidal vasculopathy.

OBJECTIVE: To study the treatment patterns and visual outcome over one year in Asian patients with choroidal neovascular membrane secondary to age-related macular degeneration (AMD-CNV) and polypoidal choroidal vasculopathy (PCV). DESIGN: Prospective cohort, non-interventional study. METHODS: 132 treatment-naïve patients who received treatment for AMD-CNV and PCV were included. All patients underwent standardized examination procedures including retinal imaging at baseline and follow-up. AMD-CNV and PCV were defined on fundus fluorescein angiography and indocyanine green angiography at baseline. Patients were treated according to standard of care.We report the visual acuity (VA) and optical coherence tomography (OCT) measurements at baseline, month 3 and month 12 The factors influencing month 12 outcomes were analyzed. MAIN OUTCOME MEASURE: Type of treatment, number of Anti-vascular endothelial growth factor (VEGF) treatments, visual outcome over one year. RESULTS: Anti-VEGF monotherapy was the initial treatment in 89.1% of AMD-CNV, but only 15.1% of PCV. The mean number of anti-VEGF injections up to month 12 was 3.97 (4.51 AMD-CNV, 3.43 PCV, p = 0.021). Baseline OCT, month 3 OCT and month 3 VA were significant in determining continuation of treatment after month 3. At month 12, mean VA improved from 0.82 (∼20/132) at baseline to 0.68 (∼20/96) at month 12 (mean gain 6.5 ETDRS letters, p = 0.002). 34.2% of eyes (38/113 eyes) gained ≥15 ETDRS letters and 14.4% (16/113 eyes) lost ≥15 ETDRS letters. There were no significant differences in visual outcome between AMD-CNV and PCV (p = 0.51). Factors predictive of month 12 visual outcome were baseline VA, baseline OCT central macular thickness, month 3 VA and age. CONCLUSIONS: There is significant variation in treatment patterns in Asian eyes with exudative maculopathy. There is significant visual improvement in all treatment groups at one year. These data highlight the need for high quality clinical trial data to provide evidence-based management of Asian AMD.

Molecular analysis and phenotypic study in 14 Chinese families with Bietti crystalline dystrophy.

PURPOSE: To investigate the clinical features and cytochrome P450 family 4 subfamily V polypeptide 2 (CYP4V2) gene mutations in 14 Chinese families with Bietti crystalline dystrophy (BCD). METHODS: Seventeen patients from 14 unrelated Chinese families with BCD were recruited for complete clinical ophthalmic examination and genetic study. The 11 exons of CYP4V2 were amplified from genomic DNA of all patients and their family members by polymerase chain reaction (PCR) and then sequenced. Exons of TIMP3 were also sequenced in BCD patient associated with choroidal neovascularization (CNV). One hundred and seventy unrelated healthy Chinese subjects were screened for mutations in CYP4V2. RESULTS: All 17 patients with BCD had mutations in CYP4V2; one of these mutations was novel (c.219T>A, p.F73L) and four other mutations had been reported. The p.F73L mutation was a commonly detected mutation in our study (seven out of 34 alleles), either in the homozygous state or in the heterozygous state. Among the patients, considerable phenotypic variability was detected, both within and between families. Screening of TIMP3 did not find any mutation in the BCD patient associated with CNV. CONCLUSION: The novel CYP4V2 c.219T>A (p.F73L) mutation may be another recurrent mutation in Chinese patients with BCD. Our study expands the mutation spectrum of CYP4V2 and characterizes novel genotype-phenotype associations in Chinese patients with BCD.

Characteristics of fundus autofluorescence and drusen in the fellow eyes of Japanese patients with exudative age-related macular degeneration.

BACKGROUND: The main purpose of this study is to investigate the characteristics of fundus autofluorescence (FAF) and area of soft drusen among the fellow eyes of unilateral typical age-related macular degeneration (typical AMD) and polypoidal choroidal vasculopathy (PCV) in Japanese patients. METHODS: FAF images were obtained from the fellow eyes of unilateral typical AMD (n = 64), unilateral PCV (n = 95), unilateral retinal angiomatous proliferation (RAP) (n = 4) and 56 control subjects, then classified into normal, minimal-change, and abnormal patterns by two graders. Interobserver variability between two graders and intraobserver variability were assessed for FAF classifications, and cases with inconsistent decisions were finally classified by the third grader. Soft drusen were segmented and their total areas were compared between the fellow eyes of typical AMD and PCV. Area(s) with increased autofluorescence were segmented to assess the relationship with soft drusen area(s). RESULTS: Assessment for interobserver variability between two graders and intraobserver variability in one grader showed substantial agreement (κ = 0.70) and almost perfect agreement (κ = 0.85), respectively. In the final decision mediated by third grader, the proportions of eyes with either minimal-change FAF pattern or abnormal FAF pattern in the fellow eyes of both typical AMD (37 cases, 58 %) and PCV (47 cases, 49 %) were significantly higher than that of the control cases (15 cases, 27 %; p < 0.01). The proportion of abnormal FAF pattern in the fellow eyes of typical AMD (20 cases, 31 %) was higher than that of PCV (15 cases, 16 %; p < 0.05). Total soft drusen areas in the fellow eyes of typical AMD (0.369 ± 0.718 mm(2)) were larger than those of PCV (0.173 ± 0.408 mm(2); p < 0.05), and those in the eyes with abnormal FAF pattern were larger than those with minimal-change FAF pattern or normal FAF pattern (p < 0.01). Image analysis revealed a relationship between increased autofluorescence and soft drusen, especially in the cases with large total soft drusen areas. CONCLUSIONS: FAF characteristics were different between the fellow eyes of unilateral typical AMD and PCV in Japan, which might be due to the difference of total soft drusen areas between them.

Different impact of high-density lipoprotein-related genetic variants on polypoidal choroidal vasculopathy and neovascular age-related macular degeneration in a Chinese Han population.

Neovascular age-related macular degeneration (nAMD) and polypoidal choroidal vasculopathy (PCV) are both major serosanguinous maculopathies among the Asian elderly. They are similar in phenotype. Genetic variants in high-density lipoprotein (HDL) pathway were discovered to be associated with AMD in two genome-wide association studies. In this study with a Chinese Han cohort, we investigated the impacts of these genetic variants on nAMD and PCV separately. The missense coding variants and previously identified variants at LIPC, ABCA1, CETP, LPL and FADS1 loci were genotyped in 157 nAMD patients, 250 PCV patients and 204 controls without any macular abnormality. The known variants in CFH, ARMS2 and near HTRA1 were also genotyped. Fasting serum cholesterol levels were determined. The variants in CFH, ARMS2 and near HTRA1 were strongly associated with both PCV (P < 10(-6), 10(-7) and 10(-7) respectively) and nAMD (P < 10(-6), 10(-16) and 10(-17) respectively). None of the studied HDL-related variants were significantly associated with nAMD. A missense variant in CETP, rs5882, was significantly associated with PCV (P = 2.73 × 10(-4)). The rs5882 GG genotype had a 3.53-fold (95% CI: 1.93-6.45) increased risk for PCV, and conferred a significantly lower serum HDL-cholesterol level for PCV patients than the AA genotype (P = 0.048). These results suggest the need to separate PCV from nAMD in association studies especially with Asian cohorts, and that the HDL pathway may involve in the pathogenesis of PCV and nAMD differently.

Tomographic fundus features in pseudoxanthoma elasticum: comparison with neovascular age-related macular degeneration in Japanese patients.

PURPOSE: To determine the retinal and subretinal features characteristic to pseudoxanthoma elasticum (PXE) compared with age-related macular degeneration by using spectral-domain optical coherence tomography (SD-OCT) in Japanese patients. METHODS: We reviewed colour fundus photographs, fluorescein angiograms, and SD-OCT images of 52 eyes (27 Japanese patients) with angioid streaks (AS) due to PXE. Then we compared the incidence of tomographic features between 24 eyes (24 patient) with choroidal neovascularization (CNV) secondary to AS and 44 eyes (44 patients) with CNV secondary to age-related macular degeneration (AMD). RESULTS: Secondary CNV was found in 44 eyes (84.6%) of 52 patients with PXE during follow-up. We found characteristic round or ovoid tubular structures with highly reflective annular lines (termed 'outer retinal tubulation' (ORT)) in 31 (70.5%) of 44 eyes with CNV, but none were found in eyes without CNV. We also found characteristic undulations of Bruch's membrane in 38 (73.1%) eyes with AS. The incidence of ORT was significantly greater in eyes with CNV secondary to AS (70.8%; P=0.005) compared with eyes with CNV secondary to AMD (34.1%). The incidence of Bruch's membrane undulation was significantly greater in eyes with CNV secondary to AS (70.8%; P<0.0001) than in eyes with CNV secondary to AMD (11.4%). CONCLUSION: SD-OCT imaging clearly revealed a greater incidence of unique lesions, including ORT and Bruch's membrane undulation, in eyes in PXE patients with CNV secondary to AS than in eyes with CNV secondary to AMD.

Clinical characteristics of reticular pseudodrusen in Korean patients.

PURPOSE: To clarify the clinical characteristics of reticular pseudodrusen in Korean patients. DESIGN: Retrospective, observational, consecutive case series. METHODS: A total of 255 eyes of 130 patients diagnosed with reticular pseudodrusen were evaluated. Reticular pseudodrusen were diagnosed by characteristic fundus findings using ophthalmoscopy, color fundus photography with blue-channel examination, near-infrared photography, red-free photography, autofluorescence imaging, fluorescein angiography, indocyanine green angiography, and spectral-domain optical coherence tomography. Age-related macular degeneration (AMD) was determined by the International Classification and Grading System. RESULTS: The mean age was 72.6 ± 9.0 years (range, 43 to 92 years). Most reticular pseudodrusen patients had bilateral disease (97.7%), with a female preponderance (86.2%). All 3 patients who showed unilateral reticular pseudodrusen had neovascular AMD in the eye with no reticular pseudodrusen. AMD was found in 183 eyes (71.8 %), among which early AMD was found in 115 eyes (45.1%), geographic atrophy was found in 41 eyes (16.1%), and neovascular AMD was found in 27 eyes (10.6%). The mean age of patients with AMD and with no AMD was 73.7 ± 9.2 years (range, 58 to 92 years) and 69.9 ± 11.7 years (range, 43 to 90 years), respectively, and there was a statistical difference between these 2 groups (P < .05). Classic choroidal neovascularization was found in 13 eyes (48.1%), and occult choroidal neovascularization was found in 14 eyes (51.9%) in the neovascular AMD group. CONCLUSIONS: Reticular pseudodrusen occurs in Koreans, and clinical manifestations of reticular pseudodrusen in Koreans did not differ significantly from those described in white persons. However, our study demonstrated a higher rate of bilaterality compared with those previously reported, and geographic atrophy was found to be associated more commonly with reticular pseudodrusen than with neovascular AMD. Ethnical differences may be associated with these findings, and further studies are required.

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

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

Estimated cases of legal blindness and visual impairment avoided using ranibizumab for choroidal neovascularization: non-Hispanic white population in the United States with age-related macular degeneration.

OBJECTIVE: To estimate the number of non-Hispanic white individuals in the United States avoiding legal blindness and visual impairment from neovascular age-related macular degeneration (AMD) with ranibizumab availability. METHODS: Modeling of visual acuity outcomes from phase 3 ranibizumab trials to incidence rates of neovascular AMD from population-based studies. RESULTS: If no treatment were given, of the 103 582 individuals developing neovascular AMD for which ranibizumab would be indicated and available, 16 268 would become legally blind in 2 years. Monthly ranibizumab would reduce the incidence of legal blindness in 2 years by 72% (95% confidence interval [CI], 70% to 74%) to 4484 individuals. If no treatment were given, 34 702 would become visually impaired. Monthly ranibizumab would reduce the incidence of visual impairment in 2 years by 37% (95% CI, 35% to 39%) to 21 919 cases. CONCLUSIONS: Ranibizumab should have a substantial effect on reducing the magnitude of legal blindness and visual impairment within 2 years after diagnosis of neovascular AMD among non-Hispanic white individuals in the United States. Although racial subgroups other than non-Hispanic whites were not considered (because there is limited information in the literature regarding incidence rates of choroidal neovascularization in other populations) and although these results assume access to and application of monthly ranibizumab for 2 years, the number of individuals developing legal blindness or vision impairment from neovascular AMD should be reduced dramatically if monthly ranibizumab is applied when indicated.

Optimising the management of choroidal neovascularisation in Asian patients: consensus on treatment recommendations for anti-VEGF therapy.

In Asian countries, age-related macular degeneration (AMD), specifically wet AMD or choroidal neovascularisation (CNV), is an important cause of blindness and visual handicap. Vascular endothelial growth factors (VEGF) play an integral role in the development of CNV and thus provide an important therapeutic target. Current treatment paradigms for neovascular AMD recognise the place of photodynamic therapy (PDT) in the management of this condition. However, combination therapy targeting different pathways to produce a synergistic effect may result in improved visual outcomes and reduced duration of treatment. Anti-VEGF therapy has greatly improved treatment outcomes in patients with CNV, and a growing body of evidence supports the role of these agents as monotherapy or in combination with PDT. In particular, anti-VEGF may be a first-line treatment option in certain types of subfoveal myopic CNV as well as for classic and occult juxtafoveal and subfoveal CNV. The implementation of evidence-based medicine into current clinical practice is paramount to improving patient care. The authors, who are also members of the Singapore Medical Retina Advisory Board, outline the consensus points and recommended treatment algorithms based on currently available knowledge to provide a structured management approach to the treatment of Asian patients with CNV.

Long-term efficacy and safety of ranibizumab administered pro re nata in Japanese patients with neovascular age-related macular degeneration in the EXTEND-I study.

PURPOSE: To evaluate the long-term efficacy and safety of ranibizumab administered pro re nata (PRN) in Japanese patients with choroidal neovascularization secondary to age-related macular degeneration during the extension phase of the EXTEND-I study. METHODS: EXTEND-I, an open-label, multicenter, Phase I / II study comprised: a single-injection (Group A); a multiple-injection (Groups A and B; the latter consisted of patients who did not participate in the single-injection phase); and an extension phase. In the extension phase, a PRN regimen of ranibizumab (0.3 or 0.5 mg) guided by monthly best-corrected visual acuity (BCVA) score and other ophthalmic examinations was employed. The efficacy variables included the mean BCVA change from Month 12 to the last visit in Group B. Safety was assessed in all patients. RESULTS: In the extension phase, efficacy was assessed only in Group B patients. The number of ranibizumab injections per year in the 0.3 and 0.5 mg Group B patients was 4.19 and 4.27, respectively. The mean BCVA change (SD) from Month 12 to the last visit was )3.6 (14.82) letters for 0.3 mg (n = 28) and )2.2 (7.92) letters for 0.5 mg groups (n = 33) in Group B. Conjunctival haemorrhage and nasopharyngitis were the most commonly reported adverse events. Of the 13 serious adverse events reported, cerebral infarction (two incidences) was suspected to be study-drug related. CONCLUSIONS: Pro re nata regimen of ranibizumab guided by monthly BCVA and other ophthalmic examinations appears effective in sustaining the BCVA gained with 12 monthly injections while reducing the number of injections during the extension phase. Ranibizumab was well tolerated during the extension phase.