Introduction: Our aim was to describe the polytherapy and multimorbidity pattern of users of anti-VEGF and dexamethasone drugs for the treatment of these conditions, and to investigate their polytherapy and multimorbidity profiles, together with adherence and the burden of care. Methods: Descriptive, population-based, pharmacoepidemiology study on the users of anti-VEGF drugs, and secondarily intravitreal dexamethasone, for the treatment of age-related macular degeneration and other vascular retinopathies in clinical practice, using administrative databases of Lazio region, Italy. We used a cohort of 50,000 residents in Lazio in 2019 with same age as comparison. Polytherapy was assessed using databases of prescribed drugs intended for outpatient use. Multimorbidity was investigated with additional sources, such as hospital discharge records, outpatient care records, and disease-specific exemptions from co-payment. Each patient was followed for 1 to 3 years from the first intravitreal injection received. Results: 16,266 residents in Lazio who received the first IVI from 1 January 2011 to 31 December 2019, with at least 1 year of observation before index date, were included. The proportion of patients with at least one comorbidity was 54.0%. Patients used an average 8.6 (SD 5.3) concomitant drugs other than anti-VEGF used for injections. A large percentage of patients (39.0%) used 10 or more concomitant drugs, including antibacterials (62.9%), drugs for peptic ulcers (56.8%), anti-thrombotics (52.3%), NSAIDs (44.0%), and anti-dyslipidaemics (42.3%). The same proportions were found across patients of all ages, probably due to high prevalence of diabetes (34.3%), especially in younger age groups. When stratified by diabetes, a comparison of multimorbidity and polytherapy with a sample of 50,000 residents of the same age found that patients receiving IVIs used more drugs and had more comorbidities, particularly in non-diabetics. Lapses of care, whether short (absence of any type of contact for at least 60 days in the first year of follow-up and 90 in the second year) or long (90 days in the first and 180 days in the second year) were common: 66% and 51.7%, respectively. Conclusions: Patients receiving intravitreal drugs for retinal conditions have high multimorbidity and polytherapy rates. Their burden of care is aggravated by the large number of contacts with the eye care system for examinations and injections. Pursuing Minimally Disruptive Medicine to optimise patient care is a difficult goal for health systems, and more research on clinical pathways and their implementation is warranted. Full article

We aimed to investigate whether a treat-and-extend regimen of intravitreal brolucizumab (6.0 mg/0.05 mL) is effective for eyes with exudative age-related macular degeneration (AMD) refractory to aflibercept for 12 months. Sixty eyes from 56 patients receiving brolucizumab for exudative AMD refractory to aflibercept were included. Patients received a mean of 30.1 aflibercept administrations for a mean 67.9-month follow-up. All patients exhibited exudation on optical coherence tomography (OCT) despite regular 4–8 weeks of aflibercept administration. Visit 1 was scheduled at the same interval from the last aflibercept injection to the baseline. The treatment interval was extended or shortened by 1–2 weeks depending on the presence or absence of exudation on OCT. After switching to brolucizumab, the follow-up interval significantly extended at 12 months (before switching: 7.6 ± 3.8 weeks vs. at 12 months: 12.1 ± 6.2 weeks, p = 1.3 × 10⁻⁷). Forty-three percent of the eyes achieved a dry macula at 12 months after switching. However, the best-corrected visual acuity did not improve at any visit. Morphologically, the central retinal thickness and subfoveal choroidal thickness significantly decreased from baseline at 12 months (p = 3.6 × 10⁻³ and 1.0 × 10⁻³, respectively). Switching to brolucizumab can be considered to extend the treatment interval in eyes with exudative AMD refractory to aflibercept. Full article

Background: Whether metformin may reduce the risk of age-related macular degeneration (AMD) requires confirmation. This study compared the risk of AMD between ever users and never users of metformin matched on propensity score (PS) in Taiwanese patients with type 2 diabetes mellitus. Methods: We enrolled study subjects from Taiwan’s National Health Insurance. A total of 423,949 patients with new onset diabetes from 1999 to 2005 were identified. After excluding ineligible patients and enrolling only patients aged between 50 and 79 years, we created 13,303 pairs of ever users and never users of metformin matched on PS. The patients were followed from 1 January 2006 to 31 December 2011. We estimated hazard ratios by Cox regression. Results: AMD was newly diagnosed in 506 ever users and 639 never users. The respective incidence rates (per 100,000 person-years) were 778.72 and 1016.62. The hazard ratio (HR) and 95% confidence interval (CI) for ever versus never users was 0.756 (0.673–0.850). While ever users were categorized by tertiles of cumulative duration (<31.8, 31.8–63.9 and >63.9 months) and cumulative dose (<947.1, 947.1–2193.5 and >2193.5 g) of metformin, a dose–response pattern was observed. For the respective tertiles of cumulative duration, the HRs (95% CIs) were 1.131 (0.961–1.330), 0.821 (0.697–0.967) and 0.464 (0.384–0.561), while compared to never users. For the respective tertiles of cumulative dose, the HRs (95% CIs) were 1.131 (0.962–1.329), 0.739 (0.624–0.876) and 0.525 (0.438–0.629). A risk reduction among ever users was observed for all tertiles of defined daily dose but was most remarkable for the third tertile with a defined daily dose of >0.64. Subgroup analyses suggested that the benefit of metformin could be similarly observed among men and women and for age subgroups of 50–64 and 65–79 years. However, patients with diabetic retinopathy would not be significantly benefited and metformin did not seem to be preventive for exudative AMD. Conclusion: In general, metformin significantly reduces the risk of AMD. Full article

Purpose: This study assessed the relationship between the choroidal morphology and short-term response to aflibercept treatment in pachychoroid neovasculopathy (PNV). Methods: This was a retrospective case-control study. Ultra-widefield indocyanine green angiography (UWICGA) and optical coherence tomography (OCT) images of 90 PNV eyes of 90 patients treated with aflibercept were enrolled. Responsiveness to aflibercept was defined as a complete resolution of sub- or intra-retinal fluid after three loading doses (50 dry and 40 non-dry eyes). Subfoveal choroidal thickness (SFCT) was measured on OCT images, and choroidal vessel density (CVD), CVD asymmetry, intervortex anastomosis, and choroidal vascular hyperpermeability (CVH) were assessed on UWICGA images. Results: CVD on UWICGA differed between groups in terms of the total area (0.323 ± 0.034 in dry vs. 0.286 ± 0.038 in non-dry, p < 0.001) and area of each quadrant (superotemporal: 0.317 ± 0.040 vs. 0.283 ± 0.040, superonasal: 0.334 ± 0.040 vs. 0.293 ± 0.045, inferonasal: 0.306 ± 0.051 vs. 0.278 ± 0.052, inferotemporal: 0.334 ± 0.047 vs. 0.290 ± 0.046; all p ≤ 0.010). The CVH grade differed between groups (mean 1.480 ± 0.735 vs. 1.875 ± 0.822, p = 0.013). ST and IT intervortex anastomoses were common in the dry group, while SN, ST, and IT were most common in the non-dry group (p = 0.001). Conclusions: A poor short-term response to aflibercept treatment in PNV eyes was associated with a lower Haller vessel density, higher CVH grade, and intervortex anastomosis involving more quadrants on UWICGA. Full article

Background: During the treatment of age-related macular degeneration with anti-vascular endothelial growth factor (VEGF) drugs, we often see cases with anti-VEGF-resistant refractory subretinal fluid. In this report, we present two cases of anti-VEGF-resistant refractory age-related macular degeneration (AMD) due to the concurrent development of central serous chorioretinopathy (CSCR) in eyes previously well controlled with intravitreal anti-VEGF injections. Case presentation: Two patients underwent intravitreal aflibercept for the treatment of neovascular AMD. Initially, both patients responded well to intravitreal aflibercept, resulting in the complete resolution of the subretinal fluid. However, both patients subsequently developed sudden-onset refractory subretinal fluid that did not respond to repeated intravitreal aflibercept. Fluorescein angiography, indocyanine green angiography, and swept-source optical coherence tomography revealed focal leakage spots, choroidal hyperpermeability, and dilated choroidal vessels, respectively, which were distinct from the pre-existing choroidal neovascularization and suggestive of newly developed CSCR. Laser photocoagulation of the leak spots resulted in the complete resolution of the once-refractory subretinal fluid and the maintenance of vision. Conclusions: Our cases highlight that anti-VEGF-refractory subretinal fluid may occur secondary to concurrent CSCR in patients receiving regular anti-VEGF treatments for AMD. In those patients, treatment for CSCR is effective for controlling subretinal fluid that is unresolved by anti-VEGF treatment. Full article