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.

What Effect Does Ethnicity Have on the Response to Ranibizumab in the Treatment of Wet Age-Related Macular Degeneration?

AIMS: To compare, in a single urban population, the visual outcomes of ranibizumab monotherapy in "White" (W) and "Non-White" (NW) patients with wet age-related macular degeneration (AMD). PROCEDURES: Prospective data was collected from 434 eyes of 217 patients with wet AMD patients receiving intravitreal ranibizumab. Baseline and monthly LogMAR visual acuities were obtained. All patients received treatment under a "treat and extend policy" consisting of three monthly injections of ranibizumab, followed by individualised sequentially lengthening follow-up intervals when stable. RESULTS: At 24 months, the percentage of eyes that maintained or improved vision was 91% in W patients and 83% in NW patients. Correspondingly, at 24 months, the percentage of visual loss was 9% for W patients and 17% of NW patients. We found that whilst W patients required fewer overall injections (14.1) they gained an average 4 LogMAR letters of visual acuity. However, NW patients required more injections (14.6) to gain 0.5 LogMAR letters of visual acuity over the same 24 months of treatment. CONCLUSIONS: Individualised ranibizumab monotherapy is more effective in preserving vision for W compared to NW patients with wet AMD.

Association of HTRA1 rs11200638 with age-related macular degeneration (AMD) in Brazilian patients.

Age-related macular degeneration is a multifactorial disease that can lead to vision impairment in older individuals. Although the etiology of age-related macular degeneration remains unknown, risk factors include age, ethnicity, smoking, hypertension, obesity, and genetic factors. Two main loci have been identified through genome-wide association studies, on chromosomes 1 and 10. Among the variants located at the 10q26 region, rs11200638, located at the HTRA1 gene promoter, has been associated with age-related macular degeneration in several populations and is considered the main polymorphism. We conducted a replication case-control study to analyze the frequency and participation of rs11200638 in the etiology of age-related macular degeneration in a sample of patients and controls from the State of São Paulo, Brazil, through polymerase chain reaction and enzymatic digestion. The frequency of the A allele was 57.60% in patients with age-related macular degeneration and 36.45% in controls (p value < 1e-07), representing a 2.369-fold higher risk factor for the disease. Both the AA and AG genotypes were observed more frequently in the age-related macular degeneration group compared to the control group (p = 1.21e-07 and 0.0357, respectively). No statistically significant results were observed after stratification in dry versus wet types or advanced versus non-advanced forms. To our knowledge, this is the first time the association between rs11200638 and overall age-related macular degeneration has been reported in South America.

Prevalence of age-related macular degeneration in an elderly UK Caucasian population-The Bridlington Eye Assessment Project: a cross-sectional study.

ImportanceThere is paucity of data on prevalence and disease asymmetry of age-related macular degeneration (AMD), particularly the earlier stages, in the UK population.Objective and PurposeTo determine the prevalence of age-related macular degeneration in an elderly Caucasian UK population.DesignCross-sectional population study, 2002-2006.ParticipantsResidents in the study area of Bridlington aged 65 years and older.MethodsFull-ophthalmic examination was undertaken in 3549 participants, of eligible 6319 Caucasian population (response rate of 56%). Non-stereoscopic Colour fundus photographs (30°) were graded masked using a modified Rotterdam Classification for 3475 (98%) participants with gradable images. Prevalence for different AMD grades were calculated. Demographic details were analysed then integrated with the AMD gradings for full analysis. Prevalence rates for the different AMD Grades were calculated, as well as the age-specific prevalences.ResultsAMD prevalence in the worst eye were 38.5% grade 0, 41.4% grade 1, 12.8% grade 2, 2.8% grade 3, and 4.6% grade 4. Geographic atrophy (grade 4a) occurred in 2.5%, and neovascular AMD (grade 4b) in 1.8%. Prevalence increased with age such that grade 4 (advanced) AMD was 2.2% in the 65-69 years group, 15.8% for the 85-90, and 21.2% for over 90 years. There was significant asymmetry between the two eyes of individuals with advanced AMD (P<0.001), such that vision loss was unilateral. Persons with more advanced AMD grades were more likely to be dissatisfied with their vision.ConclusionsAdvanced AMD occurs more commonly in the UK Caucasian population than previously reported. Significant asymmetry between the two eyes occurs in individuals with unilateral advanced AMD so that visual impairment statistics do not represent true prevalence of advanced AMD. Persons with more advanced AMD were more likely to be dissatisfied with their vision.

ASSOCIATION OF DRUSEN VOLUME WITH CHOROIDAL PARAMETERS IN NONNEOVASCULAR AGE-RELATED MACULAR DEGENERATION.

PURPOSE: The choroid is thought to be relevant to the pathogenesis of nonneovascular age-related macular degeneration, but its role has not yet been fully defined. In this study, we evaluate the relationship between the extent of macular drusen and specific choroidal parameters, including thickness and intensity. METHODS: Spectral domain optical coherence tomography images were collected from two distinct, independent cohorts with nonneovascular age-related macular degeneration: Amish (53 eyes of 34 subjects) and non-Amish (40 eyes from 26 subjects). All spectral domain optical coherence tomography scans were obtained using the Cirrus HD-OCT with a 512 × 128 macular cube (6 × 6 mm) protocol. The Cirrus advanced retinal pigment epithelium analysis tool was used to automatically compute drusen volume within 3 mm (DV3) and 5 mm (DV5) circles centered on the fovea. The inner and outer borders of the choroid were manually segmented, and the mean choroidal thickness and choroidal intensity (i.e., brightness) were calculated. The choroidal intensity was normalized against the vitreous and nerve fiber layer reflectivity. The correlation between DV and these choroidal parameters was assessed using Pearson and linear regression analysis. RESULTS: A significant positive correlation was observed between normalized choroidal intensity and DV5 in the Amish (r = 0.42, P = 0.002) and non-Amish (r = 0.33, P = 0.03) cohorts. Also, DV3 showed a significant positive correlation with normalized choroidal intensity in both the groups (Amish: r = 0.30, P = 0.02; non-Amish: r = 0.32, P = 0.04). Choroidal thickness was negatively correlated with normalized choroidal intensity in both Amish (r = -0.71, P = 0.001) and non-Amish (r = -0.43, P = 0.01) groups. Normalized choroidal intensity was the most significant constant predictor of DV in both the Amish and non-Amish groups. CONCLUSION: Choroidal intensity, but not choroidal thickness, seems to be associated with drusen volume in Amish and non-Amish populations. These observations suggest that choroidal parameters beyond thickness warrant further study in the setting of age-related macular degeneration.

HTRA1 promoter variant differentiates polypoidal choroidal vasculopathy from exudative age-related macular degeneration.

Exudative age-related macular degeneration (AMD) and polypoidal choroidal vasculopathy (PCV) share similar abnormal choroidal vasculature, but responses to treatments are different. In this study, we sequenced the whole HTRA1 gene and its promoter by direct sequencing in a Hong Kong Chinese PCV cohort. We identified rs11200638, c.34delCinsTCCT, c.59C>T, rs1049331 and rs2293870 significantly associated with PCV. Notably, rs2672598 was significantly associated with exudative AMD (p = 1.31 × 10(-4)) than PCV (p = 0.11). Logistic regression indicated that rs2672598 (p = 2.27 × 10(-3)) remained significant after adjusting for rs11200638 in exudative AMD. Moreover, the rs11200638-rs2672598 joint genotype AA-CC conferred higher risk to exudative AMD (43.11 folds) than PCV (3.68 folds). Promoter analysis showed that rs2672598 C-allele showed higher luciferase expression than wildtype T-allele (p = 0.026), independent of rs11200638 genotype (p = 0.621). Coherently, vitreous humor HTRA1 expression with rs2672598 CC genotype was significantly higher than that with TT genotype by 2.56 folds (p = 0.02). Furthermore, rs2672598 C-allele was predicted to alter the transcription factor binding sites, but not rs11200638 A-allele. Our results revealed that HTRA1 rs2672598 is more significantly associated with exudative AMD than PCV in ARMS2/HTRA1 region, and it is responsible for elevated HTRA1 transcriptional activity and HTRA1 protein expression.

Incidence of Age-Related Macular Degeneration in a Multi-Ethnic United States Population: The Multi-Ethnic Study of Atherosclerosis.

PURPOSE: To describe the incidence of age-related macular degeneration (AMD) and associated risk factors in 4 racial/ethnic groups (white, black, Hispanic, and Chinese) residing in the United States. DESIGN: Prospective cohort study. PARTICIPANTS: A total of 3811 participants, aged 46 to 86 years, from the Multi-Ethnic Study of Atherosclerosis (MESA) cohort, with retinal data collected twice, on average, 8 years apart. METHODS: Fundus images, taken using a digital camera through dark-adapted pupils using a standard protocol and the same equipment at both study visits, were graded centrally for early and late AMD on the basis of drusen size, type and area, increased retinal pigment, retinal pigment epithelial depigmentation, neovascular lesions, and geographic atrophy using the modified Wisconsin Age-Related Maculopathy Grading System. Demographic, clinical, and laboratory measures were included in multivariable regression models to determine their impact on the variation in AMD incidence among racial/ethnic groups. MAIN OUTCOME MEASURES: Incident early and late AMD. RESULTS: The overall 8-year age- and sex-standardized incidence of early and late AMD were 4.1% and 2.3%, respectively, with incidence of early and late AMD highest in whites (5.3% and 4.1%, respectively), intermediate in Chinese (4.5% and 2.2%, respectively) and Hispanics (3.3% and 0.8%, respectively), and lowest in blacks (1.6% and 0.4%, respectively). By adjusting for age and sex, blacks had a 70% lower risk of developing early AMD than whites, and this decreased only slightly to a 67% lower risk after multivariable adjustment. By adjusting for age, sex, and race/ethnicity, hyperopia was associated with early AMD (odds ratio [OR], 1.51; 95% confidence interval [CI], 1.04-2.20), as was astigmatism (OR, 1.47; 95% CI, 1.00-2.16), but not myopia (P = 0.29). Age, race/ethnicity, current smoking, hyperopia, and AMD-susceptibility genotypes Complement Factor H (CFH) RS1061170 and Age Related Maculopathy Susceptibility 2 (ARMS2) RS3793917 were independently associated with incident early AMD in multivariable models for the combined sample. However, the only statistically significant factor consistently associated with incident early AMD across the 4 racial/ethnic groups was increasing age. Risk factors for late AMD were not assessed because of its low incidence, particularly across racial/ethnic groups. CONCLUSIONS: Variation in the incidence of early AMD exists among racial/ethnic groups in the United States and is not explained by the clinical, genetic, and environmental factors included in this study.

Incidence of Late-Stage Age-Related Macular Degeneration in American Whites: Systematic Review and Meta-analysis.

PURPOSE: To estimate incidence of age-related macular degeneration (AMD) by subtype in American whites aged ≥50 years. DESIGN: Systematic review and meta-analysis. SETTING: Prospective cohort studies of AMD incidence in populations of white European ancestry published in MEDLINE, EMBASE, and Web of Science. STUDY POPULATION: Fourteen publications in 10 populations that examined AMD incident cases were identified. OBSERVATION PROCEDURE: Data on age-sex-specific incidence of late AMD, geographic atrophy (GA) and neovascular AMD (NVAMD), year of recruitment, AMD grading method, and continent were extracted. MAIN OUTCOME MEASURE(S): Annual incidence of late AMD, GA, and NVAMD by age-sex in American whites aged ≥50 years from a Bayesian meta-analysis of incidence studies was compared with incidence extrapolated from published prevalence estimates. RESULTS: Incidence rates from the review agreed with those derived from prevalence, but the latter were based on more data, especially at older ages and by AMD subtypes. Annual incidence (estimated from prevalence) of late AMD in American whites was 3.5 per 1000 aged ≥50 years (95% credible interval 2.5, 4.7 per 1000), equivalent to 293 000 new cases in American whites per year (95% credible interval 207 000, 400 000). Incidence rates approximately quadrupled per decade in age. Annual incidence GA rates were 1.9 per 1000 aged ≥50 years, NVAMD rates were 1.8 per 1000. Late AMD incidence was 38% higher in women vs men (95% credible interval 6%, 82%). CONCLUSIONS: Estimating AMD incidence from prevalence allows better characterization at older ages and by AMD subtype where longitudinal data from incidence studies are limited.

Long-term outcome of intravitreal pegaptanib sodium as maintenance therapy in Japanese patients with neovascular age-related macular degeneration.

PURPOSE: To evaluate the results of a 3-year follow-up of intravitreal pegaptanib sodium injection as maintenance therapy for the treatment of neovascular age-related macular degeneration (AMD) in Japanese patients. METHODS: In this prospective, uncontrolled interventional study, 20 eyes of 19 patients with treatment-naïve AMD who had received 3 consecutive monthly injections of 0.5 mg/0.05 mL ranibizumab as the induction treatment and had shown clinical/anatomical improvement were enrolled. An intravitreal injection of 0.3 mg/0.09 mL pegaptanib sodium was administered as the maintenance therapy every 6 weeks. Booster treatments using ranibizumab were allowed if clinical deterioration was judged to be present. The primary outcome measures were the best-corrected visual acuity (BCVA) and the central foveal thickness (CFT) as evaluated using spectral-domain optical coherence tomography. RESULTS: Sixteen of the 20 eyes (80 %) were assessed at the 3-year follow-up. The mean logMAR BCVA improved significantly from 0.56 ± 0.31 before the induction treatment to 0.24 ± 0.25 at baseline (P < 0.001) and was well maintained at 156 weeks (0.25 ± 0.28, P = 0.938). Moreover, the mean CFT also decreased significantly from 346 ± 111 µm before the induction treatment to 232 ± 54 µm at baseline (P < 0.001) and was well preserved at 156 weeks (210 ± 59 µm, P = 0.278). Thirteen eyes (81.3 %) received an unscheduled booster treatment, and no severe systemic or ocular side effects occurred during follow-up. CONCLUSION: Intravitreal pegaptanib sodium injection as the maintenance therapy was effective in stabilizing the vision of patients with AMD in whom induction treatment led to improved BCVA, as evaluated at the 3-year follow-up.

Age-related macular degeneration in ethnically diverse Australia: Melbourne Collaborative Cohort Study.

PURPOSE: To determine and compare the prevalence of age-related macular degeneration (AMD) in older Australians of Anglo-Celtic and Southern European origin. METHODS: A total of 21,132 participants of the Melbourne Collaborative Cohort Study, aged 47-86 years, were assessed for AMD in 2003-2007 with non-mydriatic fundus photography. Of these, 14% were born in Southern Europe (Greece, Italy or Malta), with the remaining 86% of Anglo-Celtic origin, born in Australia, the United Kingdom or New Zealand. RESULTS: Overall, 2694 participants (12.7%) had early stages of AMD, defined as either one or more drusen ≥ 125 µm (with or without pigmentary abnormalities) or one or more drusen 63-124 µm with pigmentary abnormalities in a 6000-µm diameter grading grid, in the absence of late AMD in either eye. A total of 122 participants (0.6%) had late AMD, defined as either geographic atrophy or neovascular AMD. In logistic regression analysis, adjusted for age, sex, smoking, education and physical activity, Southern Europeans compared to Anglo-Celts had a higher prevalence of the early stages of AMD (odds ratio, OR, 1.15, 95% confidence interval, CI, 1.00-1.34), and lower prevalence of late AMD (OR 0.36, 95% CI 0.17-0.78). CONCLUSIONS: Australians of Southern European origin have a higher prevalence of the early stages of AMD and lower prevalence of late AMD compared to those of Anglo-Celtic origin. Although AMD prevalence in the older age group(s) of Southern Europeans could be underestimated due to disparity in participation rates, it is likely that both lifestyle and genetic factors play their parts in differential AMD prevalence in these ethnic groups.

Efficacy and safety of intravitreal aflibercept injection in wet age-related macular degeneration: outcomes in the Japanese subgroup of the VIEW 2 study.

BACKGROUND/AIMS: To evaluate efficacy and safety of intravitreal aflibercept (IVT-AFL) in Japanese patients with wet age-related macular degeneration (wAMD) from the VIEW 2 trial. METHODS: In this double-masked study, patients were randomised to: 0.5 mg IVT-AFL every 4 weeks (0.5q4); 2 mg IVT-AFL every 4 weeks (2q4); 2 mg IVT-AFL every 8 weeks (2q8) after 3 monthly injections; or 0.5 mg ranibizumab every 4 weeks (Rq4). Main efficacy outcomes included vision maintenance and best-corrected visual acuity (BCVA) at week 52. RESULTS: At week 52, all Japanese patients in the IVT-AFL groups (n=70) maintained vision, compared with 96% of Japanese patients (n=23/24) treated with ranibizumab. Japanese patients in all treatment groups showed improvement in BCVA after treatment. The Rq4, 2q4 and 2q8 groups experienced similar gains in BCVA from baseline. The 0.5q4 group had higher gains due to an unexpected drop in BCVA between screening and baseline. Central retinal thickness and mean area of choroidal neovascularisation decreased in all treatment groups with similar magnitude. Ocular treatment-emergent adverse events were balanced across treatment groups. CONCLUSIONS: IVT-AFL was effective and well tolerated in Japanese patients. Outcomes in this population were consistent with those in the overall VIEW 2 population. TRIAL REGISTRATION NUMBER: NCT00637377.

Optical coherence tomography-based ranibizumab monotherapy for retinal angiomatous proliferation in Korean patients.

PURPOSE: To evaluate the visual outcome of optical coherence tomography-based ranibizumab monotherapy in Korean patients with retinal angiomatous proliferation and identify prognostic factors of visual outcome. METHODS: A prospective single-arm clinical study of 31 retinal angiomatous proliferation patients who underwent 3 consecutive monthly intravitreal ranibizumab injections was conducted. Additional treatment was given based on optical coherence tomography at monthly follow-ups over 24 months. RESULTS: Best-corrected visual acuity improved from 48.7 ± 19.3 to 56.3 ± 19.1 letters at 24 months (P = 0.010). Total cumulative numbers of injection were 5.5 ± 2.2 and 7.7 ± 3.4 times at 12 and 24 months, respectively. Older age, larger choroidal neovascularization size, and poor initial best-corrected visual acuity were associated with poor visual outcome. Final best-corrected visual acuity was significantly worse with Stage 3 disease (70.4 ± 5.1, 62.3 ± 11.6, 46.2 ± 22.3 letters improved in each stage; P = 0.015). Among factors associated with poor visual outcome, only the stage of retinal angiomatous proliferation remained statistically significant on multiple linear regression analysis (P = 0.006). Although baseline best-corrected visual acuity was similar, Stage 3 patients exhibited limited visual improvement despite anatomical improvement, and more recurrences requiring more injections. CONCLUSION: Retinal angiomatous proliferation may be successfully managed with ranibizumab monotherapy in Korean patients, with the number of treatments required comparable to other forms of neovascular age-related macular degeneration. However, visual improvement was limited in late-stage RAP.

Early signs of exudative age-related macular degeneration in Asians.

PURPOSE: To investigate the relationship between the early signs of age-related macular degeneration (AMD) and the risk of developing exudative AMD (typical AMD or polypoidal choroidal vasculopathy [PCV]) in the fellow eye of Japanese patients with unilateral exudative AMD, focusing particularly on eyes with only pigmentary abnormality. METHODS: This study is a retrospective observational consecutive case series. We retrospectively reviewed the medical charts of patients who revisited the AMD clinic from 2010 to 2011 and confirmed 129 cases with unilateral exudative AMD at their first visit (baseline). The non-affected eyes at baseline (the second eye) were categorized by the presence of early signs of AMD. The incidence of exudative AMD (typical AMD or PCV) in the fellow eye was confirmed by fluorescein and indocyanine green angiography. RESULTS: Of the 129 patients, 14 (10.9%) developed exudative AMD in the fellow eye (median follow-up, 3.2 years; n = 7 typical AMD and n = 7 PCV). Eyes with both pigmentary abnormalities and large drusen were more likely to develop typical AMD (age- and sex-adjusted odds ratio = 9.46, 95% confidence interval = 1.05 to 85.0), whereas pigmentary abnormalities without large drusen were associated with PCV (age- and sex-adjusted odds ratio = 15.9, 95% confidence interval = 1.8 to 140.5). CONCLUSIONS: There was a difference in the association between early signs of AMD and incident development of either typical AMD or PCV. Further research is warranted to determine whether pigmentary abnormalities alone may be an important risk factor for PCV in Asians.

Increased risk of Parkinson disease following a diagnosis of neovascular age-related macular degeneration: a retrospective cohort study.

PURPOSE: To investigate the risk for Parkinson disease during a 3-year follow-up period after a diagnosis of neovascular age-related macular degeneration (AMD) using a nationwide population-based dataset in Taiwan. DESIGN: A retrospective matched-cohort study. METHODS: We identified 877subjects with neovascular AMD as the study cohort and randomly selected 8770 subjects for a comparison cohort. Each subject was individually followed for a 3-year period to identify those who subsequently developed Parkinson disease. Stratified Cox proportional hazard regressions were performed as a means of comparing the 3-year risk of subsequent Parkinson disease between the study and comparison cohorts. RESULTS: The incidence rate of Parkinson disease was 5.32 (95% confidence interval [CI]: 3.03-8.72) per 1000 person-years in patients with neovascular AMD and 2.09 (95% CI: 1.59-2.70) per 1000 person-years in comparison patients. The log-rank test indicated that subjects with neovascular AMD had a significantly lower 3-year Parkinson disease-free survival rate than comparison subjects (P < .001). After censoring cases in which patients died during the follow-up period and adjusting for monthly income, geographic region, hypertension, diabetes, hyperlipidemia, and coronary heart disease, the hazard ratio of Parkinson disease during the 3-year follow-up period for subjects with neovascular AMD was 2.57 (95% CI: 1.42-4.64) that of comparison subjects. CONCLUSION: In this study, subjects with neovascular AMD were found to be at a significant risk of Parkinson disease during a 3-year follow-up period after their diagnosis among Taiwanese Chinese. Further study is needed to confirm our findings and explore the underlying pathomechanism.

Maintenance therapy with pegaptanib sodium for neovascular age-related macular degeneration: an exploratory study in Japanese patients (LEVEL-J study).

PURPOSE: To explore the efficacy and safety of pegaptanib sodium as maintenance therapy in Japanese patients with neovascular, age-related macular degeneration (AMD) after induction therapy (LEVEL-J study). METHODS: A multi-center, prospective study was conducted at 21 medical institutions between 2009 and 2011. Of Japanese neovascular AMD patients with choroidal neovascularization who showed improvement in visual acuity (VA) with induction therapy, those who were scheduled for intravitreal injections of pegaptanib as maintenance therapy were recruited. LogMAR VA was assessed. Booster treatment (unscheduled treatment with other agents) was allowed during the study period if symptoms were judged to have worsened. Safety was assessed by monitoring adverse events and intraocular pressure (IOP). RESULTS: Of 75 patients included in the analysis, 80 % completed the 54-week study period. Their mean age was 74.7 ± 6.9 years, and 54 patients (72.0 %) were men. The mean number of pegaptanib injections was 5.7 ± 2.6. Booster treatment was not required in 40 eyes (53.3 %). Mean logMAR VA was 0.61 ± 0.31 before induction therapy, 0.26 ± 0.24 before maintenance therapy, and 0.29 ± 0.28 at 54 weeks. No notable change in VA was observed during maintenance therapy. Adverse events were reported in 4 patients (5.3 %), including increased intraocular pressure, cancer, gallstones and recurrence of breast cancer, but mean IOP remained stable during maintenance therapy. CONCLUSIONS: The results of this exploratory study suggest that maintenance therapy with pegaptanib is potentially an effective and well-tolerated option in Japanese patients with neovascular AMD in whom induction therapy has been successful.

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.

Bevacizumab for neovascular age-related macular degeneration in China.

OBJECTIVE: To evaluate 2 different dosing regimens of intravitreal bevacizumab for the treatment of neovascular age-related macular degeneration (AMD) patients in China. DESIGN: Multicenter, randomized, prospective, open-label clinical trial. PARTICIPANTS: One hundred eighty-five patients with active neovascular AMD, exclusion of a macular scar, choroidal neovascularization not resulting from AMD, and polypoidal choroidal vasculopathy. INTERVENTION: Patients were assigned randomly to receive intravitreal injections of bevacizumab every 6 weeks for the first 3 injections followed by injections every 6 weeks (regimen A, n = 91) or every 12 weeks (regimen B, n = 94). MAIN OUTCOME MEASURES: The primary outcome measure was a comparison of the mean change in visual acuity from baseline. The secondary outcome measure was a comparison of the proportion of patients with a change in visual acuity of 15 letters or more. Adverse events were monitored. RESULTS: One-hundred eighty five patients were enrolled. At 48 weeks, the increase in the mean visual acuity measurements from baseline were 12.58 letters in regimen A and 10.06 letters in regimen B (P = 0.288). At 48 weeks, the percentage of eyes losing fewer than 15 letters was 96.2% in regimen A and 93.9% in regimen B (P = 0.720). At 48 weeks, the median decrease in central retinal thickness measurements from baseline was 119 µm in regimen A and 60 µm in regimen B (P = 0.221). Adverse events during the 48 weeks included anterior chamber inflammation in 17 patients (18.7%) from regimen A and 9 patients (9.6%) from regimen B (P = 0.075). There were no other notable ocular adverse events in either group. CONCLUSIONS: Intravitreal bevacizumab improved visual acuity and decreased macular thickness in patients with neovascular AMD when dosed either every 6 weeks or every 12 weeks after 3 doses given at 6-week intervals. Although there were no statistically significant differences between the 2 regimens, the results tended to favor the group dosed every 6 weeks (regimen A).

Macular pigment optical density in wet age-related macular degeneration among Indians.

PURPOSE: To estimate the value of macular pigment optical density (MPOD) in adult south Indian population with wet age-related macular degeneration (AMD). METHODS: A total of 33 patients with wet AMD and 29 age-matched controls >50 years of age underwent MPOD measurement with the macular densitometer. The patients were also tested for their dietary intake of carotenoids, smoking history, and lifetime UV exposure. RESULTS: The mean MPOD values in the Indian population with wet AMD was 0.23 (95% CI: 0.18-0.29) vs control was 0.43 (95% CI: 0.37-0.49), P<0.0001, at 0.5° eccentricity. Ex-smokers had a lower MPOD than non-smokers (0.16 (0.09-0.23) vs 0.28 (0.22-0.34), P=0.026) and the lowest level of carotenoids intake had 48% lower MPOD than the highest level (0.14 (0.08-0.21) vs 0.33 (0.24-0.43), P=0.012). There was no significant age-related decline or gender variation in MPOD. CONCLUSION: This study establishes the MPOD in adult Indian population with wet AMD, with a lack of macular pigment in association with wet AMD.