Age-related Macular Degeneration In Japan Research Articles

One-year outcomes and safety assessment of faricimab in treatment-naïve patients with neovascular age-related macular degeneration in Japan

This multicentre retrospective study evaluated the 1-year outcomes and safety profile of faricimab in treatment-naïve patients with neovascular age-related macular degeneration (nAMD). Fifty-five patients (57 eyes) underwent loading therapy comprising three monthly faricimab injections. If dryness was achieved by the third month, subsequent treat-and-extend (TAE) follow-up continued at a minimum 8-week interval thereafter. If wet macula persisted at the third month, a fourth dose was administered, followed by the TAE regimen. After 1 year, improvements in visual acuity (0.44 ± 0.46 [baseline] to 0.34 ± 0.48; p < 0.01) and central foveal thickness (326 ± 149 [baseline] to 195 ± 82 μm; p < 0.0001) were significant. Dry macula, characterised by the absence of intraretinal or subretinal fluid, was achieved in 65% of cases. Treatment intervals varied, ranging from 8 to 16 weeks, with 44% of eyes extending to a 16-week interval, followed by 33% at 8 weeks, 16% at 12 weeks, 5% at 14 weeks, and 2% at 10 weeks. Notably, 50% of the polypoidal choroidal vasculopathy patients exhibited complete regression of polypoidal lesions between 12 and 15 months. Faricimab treatment in nAMD patients induced significant improvements in central vision and retinal morphology. Two cases of retinal pigment epithelial tears and one case of iritis were reported as ocular complications.

Recent evidence of economic evaluation of artificial intelligence in ophthalmology.

Health economic evaluation (HEE) is essential for assessing value of health interventions, including artificial intelligence. Recent approaches, current challenges, and future directions of HEE of artificial intelligence in ophthalmology are reviewed. Majority of recent HEEs of artificial intelligence in ophthalmology were for diabetic retinopathy screening. Two models, one conducted in the rural USA (5-year period) and another in China (35-year period), found artificial intelligence to be more cost-effective than without screening for diabetic retinopathy. Two additional models, which compared artificial intelligence with human screeners in Brazil and Thailand for the lifetime of patients, found artificial intelligence to be more expensive from a healthcare system perspective. In the Thailand analysis, however, artificial intelligence was less expensive when opportunity loss from blindness was included. An artificial intelligence model for screening retinopathy of prematurity was cost-effective in the USA. A model for screening age-related macular degeneration in Japan and another for primary angle close in China did not find artificial intelligence to be cost-effective, compared with no screening. The costs of artificial intelligence varied widely in these models. Like other medical fields, there is limited evidence in assessing the value of artificial intelligence in ophthalmology and more appropriate HEE models are needed.

Three-month outcomes of faricimab loading therapy for wet age-related macular degeneration in Japan

This multicenter study aimed to assess the short-term effectiveness and safety of faricimab in treatment-naïve patients with wet age-related macular degeneration (wAMD) in Japan. We retrospectively reviewed 63 eyes of 61 patients with wAMD, including types 1, 2, and 3 macular neovascularization as well as polypoidal choroidal vasculopathy (PCV). Patients received three consecutive monthly intravitreal injections of faricimab as loading therapy. Over these 3 months, visual acuity improved gradually compared to baseline. Moreover, the central foveal thickness decreased significantly at 1, 2, and 3 months compared to baseline (p < 0.0001). At 3 months after initiation of faricimab therapy, a dry macula (defined as absence of intraretinal or subretinal fluid) was achieved in 82% of the eyes. Complete regression of polypoidal lesions was observed in 52% of eyes with PCV. Subfoveal choroidal thickness also decreased significantly at 1, 2, and 3 months compared to baseline (p < 0.0001). Although retinal pigment epithelium tears developed in two eyes, there were no other ocular or systemic complications observed during the 3 months of loading therapy. In conclusion, loading therapy using faricimab resulted in improved visual acuity and retinal morphology in Japanese patients with wAMD without particular safety issues.

Cost-Effectiveness Analysis of Ranibizumab Biosimilar for Neovascular Age-Related Macular Degeneration in Japan.

Neovascular age-related macular degeneration (nAMD) is the world's leading cause of blindness in elderly people. While anti-vascular endothelial growth factor (VEGF) treatments are used as the first option for patients with nAMD, they are generally expensive and need repeated injections. This study aimed to evaluate the cost-effectiveness of anti-VEGF therapies, focusing on the newly launched ranibizumab biosimilar (RBZ BS) in patients with nAMD from a Japanese societal perspective. A Markov model was developed to simulate the lifetime transitions of a cohort of treatment-naïve patients with nAMD through health states that were based on the involvement of nAMD (single eye vs. both eyes), the treatment status of the patients, and decimal best-corrected visual acuity. The model compared RBZ BS with branded RBZ, aflibercept (AFL), and AFL as loading dose switched to RBZ BS in maintenance in the treat-and-extend (TAE) regimen (RBZ TAE, AFL TAE, and AFL to RBZ BS TAE, respectively), and with branded RBZ in the pro re nata (PRN) regimen, as well as best supportive care (BSC). All processes were validated by five clinical experts. When TAE regimens were compared, RBZ BS was dominant (higher quality-adjusted life-years (QALYs) and lower total cost) to AFL TAE and AFL to RBZ TAE. The result was robust regardless of whether the clinical data were taken from the direct head-to-head clinical trial or from indirect treatment comparison. RBZ BS TAE was cost-saving compared to RBZ TAE. RBZ BS TAE was estimated to be dominant to BSC owing to a lower societal cost. Like TAE regimens, RBZ BS was cost-saving compared to RBZ PRN and was dominant to BSC in PRN regimens. This study suggests that RBZ BS is dominant to other anti-VEGF treatments in patients with nAMD in both TAE and PRN regimens and BSC from a Japanese societal perspective.

Efficacy and Safety of Intravitreal Aflibercept Treat-and-Extend Regimens in the ALTAIR Study: 96-Week Outcomes in the Polypoidal Choroidal Vasculopathy Subgroup.

IntroductionTo explore the efficacy and safety of intravitreal aflibercept (IVT-AFL) proactive, individualized treat-and-extend (T&E) regimens in exudative age-related macular degeneration (AMD) in the subgroup of patients with polypoidal choroidal vasculopathy (PCV) enrolled in the ALTAIR study.MethodsThis was a PCV subgroup analysis of ALTAIR, a 96-week, randomized, open-label, phase 4 study in treatment-naïve patients with exudative AMD in Japan. Following three initial monthly doses, patients received IVT-AFL at week 16 and were randomized 1:1 to T&E regimens with either 2-week (IVT-AFL-2W) or 4-week (IVT-AFL-4W) adjustments. The primary endpoint of ALTAIR was the mean change in best-corrected visual acuity (BCVA) from baseline to week 52. Endpoints were assessed at weeks 52 and 96. Safety analyses were conducted.ResultsA total of 90 patients with PCV were included within the full analysis set. From baseline to week 52, mean [standard deviation (SD)] change in BCVA was + 7.5 (14.7) letters and + 8.2 (11.6) letters in the IVT-AFL-2W and IVT-AFL-4W groups, respectively. From baseline to week 96, 91.3% and 90.9% of patients maintained vision in the IVT-AFL-2W and IVT-AFL-4W groups, respectively. From baseline to week 52, mean (SD) change in central retinal thickness was − 153 (177) µm and −112 (122) µm in the IVT-AFL-2W and IVT-AFL-4W groups, respectively. Overall, 51.1% of patients (IVT-AFL-2W, 43.5%; IVT-AFL-4W, 59.1%) achieved a treatment interval of 16 weeks between weeks 16 and 96. The safety profile of IVT-AFL was consistent with previous studies.ConclusionIn treatment-naïve patients with PCV, IVT-AFL administered using two different T&E regimens improved and maintained functional and anatomic outcomes over 96 weeks while minimizing treatment burden.Trial registrationClinicalTrials.gov identifier, NCT02305238.Supplementary InformationThe online version contains supplementary material available at 10.1007/s12325-022-02162-w.

Effectiveness of Current Treatments for Wet Age-Related Macular Degeneration in Japan: A Systematic Review and Pooled Data Analysis.

PurposeWe conducted a systematic review to investigate the effectiveness of clinical treatments for wet age-related macular degeneration (wAMD) in Japanese patients in the decade since anti-vascular endothelial growth factor (VEGF) therapies were introduced.MethodsPubMed was searched for articles published in English between 1 January 2008 and 30 September 2018 using a multistring search strategy. Reviews were scanned for additional relevant studies and select gray literature was evaluated. Mean and/or median for the logarithm of the minimum angle of resolution (logMAR) visual acuity (VA), central retinal thickness (CRT), and the number of injections after 12 months of treatment were calculated using extracted data. Data were stratified by disease type and treatment modality.ResultsOf 335 studies identified, 94 were selected for data extraction (147 treatment arms; typical AMD, n = 25; polypoidal choroidal vasculopathy [PCV], n = 85). Mean (median) logMAR VA was 0.44 (0.32) for typical AMD and 0.34 (0.31) for PCV; the respective mean number of anti-VEGF injections was 5.6 and 4.6. The mean CRT was approximately 220 μm for both groups. For typical AMD, anti-VEGF monotherapy resulted in better VA outcomes than photodynamic therapy (PDT) alone. For PCV, anti-VEGF monotherapy or anti-VEGF plus PDT combination therapy resulted in better VA and CRT outcomes than PDT monotherapy. Combination therapy required fewer injections than anti-VEGF monotherapy (PCV, 3.2 versus 5.3).ConclusionwAMD treatment has advanced dramatically in the years since anti-VEGF drugs were introduced in Japan. Discrete patient populations may benefit from differing management regimens, including the fewer injections required with combination therapy.

Questionnaire Survey on Driving among Patients with Age-Related Macular Degeneration in Japan.

Purpose: This study aimed to assess driving capabilities in patients with exudative age-related macular degeneration (AMD) causing unilateral blindness or paracentral scotoma without vision deterioration. Methods: Of the 275 patients with AMD who responded to a questionnaire regarding car driving at Osaka University Hospital, we excluded 78 patients who answered that they had never driven. Finally, 197 patients were included (50 with bilateral and 142 with unilateral AMD). We investigated the relationship between the questionnaire findings and best-corrected visual acuity (BCVA). Results: The mean age was 74.8 ± 6.9 years, and the mean BCVA in the right and left eyes were 0.48 and 0.47, respectively. A negative correlation was observed between the proportion of patients who stopped driving due to AMD and the vision in the worse eye (p < 0.0001); however, 66% of participants were still driving. Regardless of the BCVA, 84% of them wished to continue driving. Concerning perceived dangerous situations, all patients reported an oversight of people or signals and night driving; further, patients with unilateral and bilateral vision deterioration reported vision narrowness and difficulty with discerning signal colours, respectively. Conclusion: Despite the associated danger, patients with AMD continued driving. Close attention should be paid to the driving activities among patients with AMD, even if they have passed the relevant driving tests.

Five-year follow-up of fundus autofluorescence and retinal sensitivity in the fellow eye in exudative age-related macular degeneration in Japan.

To assess the 5-year change in abnormal fundus autofluorescence (FAF) patterns and retinal sensitivity in the fellow eye of Japanese patients with unilateral exudative age-related macular degeneration (AMD). Patients with unilateral exudative AMD who developed abnormal FAF in the fellow eyes were enrolled. FAF imaging and microperimetry were performed at baseline and follow-ups. FAF findings were classified into 8 patterns based on the International Fundus Autofluorescence Classification Group to assess retinal sensitivity. Forty-five points covering the central 12 degrees on microperimetry were superimposed onto the FAF images. Each point was classified depending on the distance from the abnormal FAF. "Close" was defined as the portion within 1 degree from the border of any abnormal FAF, and "Distant" was defined as the portion over 1 degree from the border of abnormal FAF. To investigate the association between the retinal sensitivity and distance from the abnormal FAF, hierarchical linear mixed-effect models were used with the distance, time and time squared from baseline (months), and angle (degrees) as fixed effects. Differences among patients, eyes, and test point locations were considered successively nested random effects. We studied 66 fellow eyes with abnormal FAF. Twenty-seven eyes were followed-up during the 5 years. In the 13 of 27 eyes (48%), the abnormal FAF patterns had changed during the 5 years. We found retinal sensitivity was associated significantly with the distance from the abnormal FAF ("Distant": p<0.001, time2 from baseline: p<0.001, angle: p<0.001). The mean retinal sensitivity of the "Close" tended to deteriorate after the third year and eventually showed the similar sensitivity as the portion within the abnormal FAF. FAF patterns can change about half during the 5 years and the retinal sensitivity near abnormal FAF tends to deteriorate after the third year.

Fundus autofluorescence and retinal sensitivity in fellow eyes of age-related macular degeneration in Japan.

PurposeAbnormal fundus autofluorescence (FAF) potentially precedes onset of late age-related macular degeneration (AMD) in Caucasian patients. Many differences exist between Asian and Caucasian patients regarding AMD types and severity, gender, and genetic backgrounds. We investigated the characteristics of abnormal FAF and retinal sensitivity in the fellow eyes of Japanese patients with unilateral neovascular AMD.MethodsSixty-six patients with unilateral neovascular AMD and abnormal FAF in the fellow eye were enrolled in this multicenter, prospective, observational study. The best-corrected visual acuity, fundus photographs, FAF images, and retinal sensitivity on microperimetry were measured periodically for 12 months. The FAF images were classified into eight patterns based on the International Fundus Autofluorescence Classification Group. The points measured by microperimetry were superimposed onto the FAF images and fundus photographs and classified as “within,” “close,” and “distant,” based on the distance from the abnormal FAF and other findings. The relationship between the location of the baseline abnormal FAF and retinal sensitivity was investigated.ResultsIn Japanese patients, patchy (33.3%) and focally increased (30.3%) patterns predominated in the abnormal FAF. Intermediate-to-large drusen was associated predominantly with hyperfluorescence and hypofluorescence. Neovascular AMD developed within 1 year in six (9.1%) eyes, the mean baseline retinal sensitivity of which was 12.8 ± 4.7 dB, significantly (p<0.002) lower than the other eyes. In 44 of the other 60 eyes, microperimetry was measurable at baseline and month 12 and the mean retinal sensitivity improved significantly from 13.5 ± 4.4 to 13.9 ± 4.8 dB (p<0.001), possibly associated with lifestyle changes (e.g., smoking cessation, antioxidant and zinc supplementation). The mean retinal sensitivities of points within and close to the abnormal FAF were 9.9 and 11.7 dB, respectively, which were significantly lower than the 14.0 dB of the points distant from the abnormal FAF.ConclusionIn Japanese patients, patchy and focally increased patterns predominated in the abnormal FAF. The retinal sensitivity was lower close to/within the abnormal FAF. FAF and microperimetry are useful to assess macular function before development of neovascular AMD or geographic atrophy.

One-Year Outcomes of a Treat-and-Extend Regimen of Aflibercept for Exudative Age-Related Macular Degeneration

Purpose: The aim of this study was to investigate the 1-year outcomes of treat-and-extend aflibercept for exudative age-related macular degeneration (AMD) in Japan. Procedures: Clinical records of 67 patients (67 eyes) were reviewed. Monthly aflibercept was administered until resolution of exudation and maximal reduction of pigment epithelial detachment. Injection intervals were extended by 2-week units up to 12 weeks if no exudation was observed and shortened for recurrence. Results: Mean best-corrected visual acuity (logarithm of the minimum angle of resolution) improved from 0.29 to 0.14 at 12 months (p < 0.0001). Mean central retinal thickness decreased from 430 μm to 236 μm at 12 months (p < 0.0001). Fifty-nine eyes (88.0%) achieved a dry macula with a mean of 8.3 injections by study end. The injection interval was extended to 10 weeks in 44.8% and to 12 weeks in 17.9% of eyes. Conclusions: At 1 year, good outcomes were obtained using treat-and-extend aflibercept for exudative AMD in Japan.

Cost-effectiveness of intravitreal aflibercept versus other treatments for wet age-related macular degeneration in Japan

Objective: This analysis estimated the cost-effectiveness of intravitreal aflibercept injection(s) (IAI) for wet age-related macular degeneration (wAMD) compared with other treatments in Japan.Methods: This was a cost-utility analysis based on published data. A state-transition cohort model was constructed with six health states based on best-corrected visual acuity in the better-seeing eye. The cycle time was 4 weeks, and the time horizon was 12 years. The model compared IAI 2 mg every 8 weeks (2q8) for 2 years after three initial monthly injections, ranibizumab as needed, ranibizumab 0.5 mg every 4 weeks (0.5q4), pegaptanib sodium 0.3 mg every 6 weeks, verteporfin photodynamic therapy (PDT), and best supportive care, assumed to include medical management and monitoring, but no active therapy. Costs (expressed as Japanese yen [JPY]) and quality-adjusted life years (QALYs) gained were estimated for each treatment and discounted at 2.0%. Input data were obtained from clinical studies, the Japanese drug tariff and social insurance reimbursement schedule, and expert opinion. The analysis was conducted from the societal perspective, including medical costs as well as costs of blindness.Results: IAI 2q8 was dominant (i.e. more effective in terms of QALYs and less costly) to all other comparators (ranibizumab as needed, ranibizumab 0.5q4, pegaptanib sodium, PDT, and best supportive care), as shown by the incremental cost-utility ratio (i.e. cost per QALY gained).Limitations: The strengths of the analysis include the wide range of comparators evaluated and the use of Japanese-specific utility data. The limitations include the use of one eye, inclusion of published data up to 2 years only, and assumptions on disease course over 5 years.Conclusions: IAI 2q8 was more effective in terms of QALYs and less costly compared with other treatments for wAMD in Japan.

Patient burden, treatment patterns, and visual acuity associated with neovascular age-related macular degeneration in Japan

Patient burden, treatment patterns, and visual acuity associated with neovascular age-related macular degeneration in Japan

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

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. Analysis of national insurance claims data. People 40 years of age or older who were registered in the Japan Medical Data Center database. 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. Changes in treatment patterns and health care costs in Japan. 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 in2035. 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.

Dietary n-3 Fatty Acid, α-Tocopherol, Zinc, vitamin D, vitamin C, and β-carotene are Associated with Age-Related Macular Degeneration in Japan.

This case-control study reports the association between nutrient intake and neovascular age-related macular degeneration (AMD) in Japan. The nutrient intake of 161 neovascular AMD cases from two university hospitals and 369 population-based control subjects from a cohort study was assessed using a brief-type self-administered questionnaire on diet history, which required respondent recall of the usual intake of 58 foods during the preceding month. Energy-adjusted nutrient intake values were compared between the groups. Logistic regression analysis was used to estimate odds ratios (ORs) and 95% CIs adjusted for smoking history, age, sex, chronic disease history, supplement use, and alcohol consumption. Logistic regression analysis demonstrated that low intakes of n-3 fatty acid, α-tocopherol, zinc, vitamin D, vitamin C, and β-carotene were associated with neovascular AMD (Trend P < 0.0001 for n-3 fatty acid, Trend P < 0.0001 for α-tocopherol, Trend P < 0.0001 for zinc, Trend P = 0.002 for vitamin D, Trend P = 0.04 for vitamin C, Trend P = 0.0004 for β-carotene). There was no association with retinol or cryptoxanthin intake and neovascular AMD (P = 0.67, 0.06).

The Clinical Effectiveness and Cost-Effectiveness of Screening for Age-Related Macular Degeneration in Japan: A Markov Modeling Study.

ObjectiveTo investigate the cost-effectiveness of screening and subsequent intervention for age-related macular degeneration (AMD) in Japan.MethodsThe clinical effectiveness and cost-effectiveness of screening and subsequent intervention for AMD were assessed using a Markov model. The Markov model simulation began at the age of 40 years and concluded at the age of 90 years. The first-eye and second-eye combined model assumed an annual state-transition probability, development of prodromal symptoms, choroidal neovascularization (CNV), and reduction in visual acuity. Anti–vascular-endothelial-growth-factor (anti-VEGF) intravitreal injection therapy and photodynamic therapy (PDT) were performed to treat CNV. Intake of supplements was recommended to patients who had prodromal symptoms and unilateral AMD. Data on prevalence, morbidity, transition probability, utility value of each AMD patient, and treatment costs were obtained from published clinical reports.ResultsIn the base-case analysis, screening for AMD every 5 years, beginning at the age of 50 years, showed a decrease of 41% in the total number of blind patients. The screening program reduced the incidence of blindness more than did the additional intake of supplements. However, the incremental cost-effectiveness ratio (ICER) of screening versus no screening was 27,486,352 Japanese yen (JPY), or 259,942 US dollars (USD) per quality-adjusted life year (QALY). In the sensitivity analysis, prodromal symptom-related factors for AMD had great impacts on the cost-effectiveness of screening. The lowest ICER obtained from the best scenario was 4,913,717 JPY (46,470 USD) per QALY, which was approximately equal to the willingness to pay in Japan.ConclusionsOphthalmologic screening for AMD in adults is highly effective in reducing the number of patients with blindness but not cost-effective as demonstrated by a Markov model based on clinical data from Japan.

PRM54 - Usefulness of a Commercial Hospital Claims Database to Identify Current Anti-Vascular Endothelial Growth Factor Treatment Patterns in Patients with Exudative Age-Related Macular Degeneration in Japan

PRM54 - Usefulness of a Commercial Hospital Claims Database to Identify Current Anti-Vascular Endothelial Growth Factor Treatment Patterns in Patients with Exudative Age-Related Macular Degeneration in Japan

Use of Micronutrient Supplement for Preventing Advanced Age-Related Macular Degeneration in Japan

Use of Micronutrient Supplement for Preventing Advanced Age-Related Macular Degeneration in Japan