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Purpose: To investigate differences in the incidence of retinal fluid subtypes among different subtypes of macular neovascularization (MNV) and evaluate the influence of the presence of retinal fluid subtypes on visual outcome in each subtype of MNV. Methods: This retrospective study included 248 patients (248 eyes) diagnosed with treatment-naive neovascular age-related macular degeneration and polypoidal choroidal vasculopathy (PCV). The incidence of retinal fluid subtypes at diagnosis and during the 24-month follow-up was compared among the different subtypes of MNV. In addition, visual acuity was compared between patients with and without the retinal fluid subtypes. Results: At diagnosis, there was a significant difference in the incidence of subretinal fluid (SRF), intraretinal fluid (IRF), and subretinal pigment epithelial fluid among type 1 MNV, type 2 MNV, type 3 MNV, and PCV ( P  < 0.001). The incidence of SRF ( P  < 0.001) during follow-up also differed among the 4 groups. In patients with type 1 MNV and IRF, the visual acuity at diagnosis ( P  = 0.004) and at 24 months ( P  < 0.001) were significantly worse. However, the presence of SRF was not associated with poor visual acuity. In type 3 MNV, there was no significant difference in visual acuity between patients with and without SRF/IRF. Conclusion: The results of this study indicate that the clinical significance of retinal fluid subtypes may differ in different subtypes of MNV, suggesting the need for analysis in isolation of each MNV subtype in fluid-based prognostication.

Aims: To identify the association between ranibizumab and risk of stroke and acute myocardial infarction (AMI) in patients with exudative age-related macular degeneration (AMD)., Methods: We identified patients aged ≥45 years who received ranibizumab for exudative AMD from the Korean National Health Insurance database. Of these, we selected patients suffering stroke or AMI for the self-controlled case series. We estimated incidence rate ratios (IRR) for stroke or AMI by comparing incidence rates of ranibizumab-exposed periods to that of baseline using conditional Poisson regression. The risks of haemorrhagic and ischaemic strokes were also calculated separately., Results: Among 33 134 patients receiving ranibizumab, 2397 patients had stroke or AMI. The risk of stroke (IRR=0.83, 95% CI 0.75 to 0.91) was not increased during the overall exposed period; however, there was a marginally elevated risk in ≥57 days exposed period (IRR=1.14, 95% CI 1.001 to 1.31). When analysing by the types of stroke, no increased risks of haemorrhagic (IRR=1.01, 95% CI 0.80 to 1.26) and ischaemic stroke (IRR=0.78, 95% CI 0.71 to 0.86) were observed during the exposed period, although the risks of ischaemic and haemorrhagic stroke were slightly elevated during ≥57 days exposed period. We could not find an association between ranibizumab and AMI., Conclusions: Ranibizumab intravitreal injections did not increase the overall risk of stroke or AMI. Although the cardiovascular risk in patient receiving ranibizumab seems to be low, continuous monthly use of ranibizumab for high-risk patients should be judged carefully., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: To evaluate the risk of stroke associated with intravitreal ranibizumab in age-related macular degeneration (AMD)., Methods: A nationwide retrospective case-crossover study was performed using data from the Korean National Health Insurance Service (KNHIS) database, which included patients with exudative AMD in South Korea (n = 41,860). The index date was the date of hospitalization for stroke. We defined the case period as 60 days and four control periods before the index date. A pharmacy prescription database was searched for ranibizumab use during the case and control periods. We calculated adjusted odds ratios (ORs) and 95% confidence intervals (CIs) with a conditional logistic regression model., Results: A total of 865 patients with AMD and incident stroke were included. Of all the patients, 12.02% had been treated during the preceding 60-day case period, compared with 9.25-10.29% during control periods. The adjusted OR of stroke associated with intravitreal ranibizumab during the case period was 1.285 (95% CI 0.979-1.686) (p = 0.07). In the subgroup analysis, the risk of hemorrhagic stroke had an OR of 2.252 (95% CI 1.068-4.749, p = 0.033). Further analyses based on patient gender, age, and different risk periods of 15 and 30 days yielded no increase in the risk of stroke associated with intravitreal ranibizumab., Conclusions: This case-crossover analysis revealed no evidence of increased risk of hospitalization for stroke within 60 days of intravitreal ranibizumab injection in AMD patients. A secondary analysis indicated the possibility of an increased risk of hemorrhagic stroke, with borderline significance. Further research is needed regarding the underlying biological mechanisms and drug safety.

Background/aim: The aim of this study was to estimate the nationwide incidence of clinically diagnosed exudative age-related macular degeneration (AMD) and associated use of ranibizumab and aflibercept in South Korea., Methods: In this retrospective, population-based cohort study, claims data for 2010-2015 were analysed in a randomly selected sample of 519 661 adults aged ≥40 years. The incidence per 10 000 person-years was estimated, along with the 95% CI. Incident exudative AMD was defined based on the registration code for rare intractable diseases. Use of ranibizumab and aflibercept and the incidence of exudative AMD were recorded., Results: Nine hundred and twelve patients were newly diagnosed with exudative AMD in 2010-2015. The 6-year incidence in the general population aged ≥40 years was 2.9 (95% CI 2.8 to 3.0) per 10 000 person-years. The incidence was highest in individuals aged 75-79 years (12.0, 95% CI 10.3 to 13.8). The incidence was higher in men than in women in all age groups. Six hundred and twenty-five (69%) of the 912 newly diagnosed patients started ranibizumab or aflibercept as a first-line treatment. The average number of injections administered was 6.1 (SD 3.9; minimum of 1 injection and maximum government-supported limit of 14) during 2010-2015; the number increased with increasing government funding support (from 5 to 10 and from 10 to 14 in 2013 and 2014, respectively)., Conclusions: This study describes the incidence of exudative AMD in South Korea and its treatment under the national health insurance system in this country. Its findings could be used for reference purposes and be useful when planning treatment for exudative AMD., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: The association between long-term cardioprotective aspirin use and neovascular age-related macular degeneration (AMD) is controversial. This study was undertaken to estimate the risk of neovascular AMD with long-term regular use of low-dose aspirin., Design: Retrospective population-based study, using a nationwide cohort from a variety of clinics and hospitals in South Korea., Participants: Nonregular aspirin users and regular aspirin users under national health insurance, aged ≥45 years, who were followed from 2010 to 2015, were identified., Methods: Incidence per 10 000 person-years for neovascular AMD was estimated. Long-term regular use of low-dose aspirin was defined as sustained intake of ≤100 mg aspirin with ≥1044 days prescription between 2005 and 2009. Nonregular aspirin users included occasional users or nonusers. The analyses included a propensity score-adjusted analysis in a large, randomly selected, unmatched whole cohort (n = 482 613); propensity score-matched analysis in a matched cohort (n = 74 196); and maximally adjusted analysis in the unmatched whole cohort (n = 482 613)., Main Outcome Measures: Incidence of newly developed neovascular AMD using the registration code for intractable disease under national health insurance., Results: Incidence of neovascular AMD was 3.5 among nonregular aspirin users and 7.2 among regular aspirin users per 10 000 person-years in the unmatched whole cohort. However, propensity score-adjusted analyses revealed no association between aspirin use and neovascular AMD (adjusted hazard ratio [HR], 0.98; 95% confidence interval [CI], 0.73-1.30). Likewise, propensity score-matched analyses showed no association; incidences of neovascular AMD were 7.5 and 7.1 among nonregular aspirin users and regular aspirin users (crude HR, 0.94; 95% CI, 0.70-1.28), respectively. A maximally adjusted model, including age, sex, income, residential area, and history of 100 randomly selected types of generic drugs, showed no association (adjusted HR, 0.95; 95% CI, 0.71-1.28)., Conclusions: We found no association between long-term regular use of low-dose aspirin for 5 years and future incidence of neovascular AMD. Thus, this large-scale study suggests that regular, long-term use of low-dose aspirin appears to be safe with respect to the new development of neovascular AMD., (Copyright © 2018 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Purpose: To investigate the association between genetic risk variants for age-related macular degeneration (AMD) and response to intravitreal ranibizumab in Korean patients with neovascular AMD., Methods: This prospective study included 273 treatment-naive patients (273 eyes) who underwent 5 monthly injections (Months 0, 1, 2, 3, and 4) of intravitreal ranibizumab for neovascular AMD. Patients were genotyped for 23 single-nucleotide polymorphisms within 12 AMD-relevant genes. For each polymorphism, genotypic association with good response at Month 5, predetermined as visual improvement of ≥ 8 Early Treatment Diabetic Retinopathy Study letters from baseline, was investigated with logistic regression analysis adjusted for age, gender, smoking, baseline Early Treatment Diabetic Retinopathy Study letter, central retinal thickness, lesion area, and type of choroidal neovascularization., Results: At Month 5, visual acuity improved by 9.1 ± 17.6 letters from baseline, and 136 patients (49.8%) were classified as good responders. In logistic regression, no tested polymorphism showed statistically significant association with favorable visual outcome at Month 5. When unadjusted for multiple tests, AA genotype for VEGF rs699947 had an increased chance of good response compared with other genotypes (odds ratio, 3.61; 95% confidence interval, 1.42-9.18; P = 0.0071)., Conclusion: In this Korean neovascular AMD cohort, there was no statistically significant effect of genotype on early visual outcome after ranibizumab treatment.