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To evaluate the outcomes of a 6-month follow-up after switching to brolucizumab from aflibercept to treat neovascular age-related macular degeneration (AMD) in Japanese patients.Retrospective observational study.We studied 45 consecutive eyes of 42 patients diagnosed with neovascular AMD, who were switched to intravitreal brolucizumab injection (IVBr) after receiving intravitreal aflibercept injection (IVA) using a treat-and-extend (TAE) regimen. Patients who had brolucizumab-associated intraocular inflammation (IOI) were excluded from the study. The mean changes in the logarithm of the minimum angle of resolution (logMAR) best-corrected visual acuity (BCVA), central foveal thickness (CFT), central choroidal thickness (CCT), and treatment intervals were evaluated at 6 months after the switch to IVBr.One eye of 1 patient was excluded because of IOI after the switch; 44 eyes of 41 patients were enrolled in this study. The mean logMAR BCVA was maintained throughout the follow-up period when compared with the baseline value (P .05 at 6 months). However, the mean CFT and CCT at 6 months had decreased significantly (P .05 and P .001, respectively). The mean treatment interval was extended from 5.75 to 8.12 weeks.Switching to brolucizumab from aflibercept using a TAE regimen might be effective for maintaining functional outcomes and extending intervals in Japanese patients with AMD.

To identify patient preference drivers related to the management of wet age-related macular degeneration (wet AMD).In this cross-sectional study, a self-explicated 'conjoint analysis' survey was administered online to eligible patients with wet AMD (receiving anti-vascular endothelial growth factor [VEGF] treatment for at least 12 months) from the USA, Canada, UK, France, Spain, Germany, Italy, Japan, Taiwan, and Australia. The survey consisted of six domains with 21 attributes, which were selected on the basis of a literature review, social media listening, and tele-interviews/discussions with patients, clinical experts, and patient groups. Utility and relative importance scores were generated for each attribute and utility difference significance testing was performed using 'unequal variances t tests'. The Patient Activation Measure (PAM-13) questionnaire was administered to assess patients' knowledge, skill, and confidence in self-management.A total of 466 patients (mean age, 68 years; women, 54%; binocular wet AMD, 28%) with an average anti-VEGF treatment duration of 3.9 years completed the survey. The most important preference domains were 'treatment effects on vision' (non-significant) and 'vision-related symptom burdens' (p 0.001), followed by 'treatment risk' (p 0.05), 'impact on daily activities' (p 0.05), 'burden of clinic/hospital visits' (p 0.001), and 'impact on psychological well-being'. The five most important attributes in order of importance were clarity of vision, treatment effect on symptoms, quality of vision, time to treatment effect, and time to re-administration. The two most important attributes globally were also in the top three attributes across countries. The majority of participants in the study were level 3 or level 4 of the PAM-13 questionnaire.This study identified the most important disease and treatment attributes to patients using patient-centred methods. The data showed the degree of harmonization of preferences across geographies and that participants actively adopt behaviours required for improved treatment outcomes. The identified preference drivers may inform future clinical development.

This study aimed to report the visual and anatomical outcomes of intravitreal anti-VEGF treatment for diabetic macular edema (DME) in a real-world clinical setting from Turkey over 36 months.This is a retrospective, multicenter (7 sites) study. The medical records of 1072 eyes (both previously treated and naive eyes) of 706 consecutive patients with visual impairment due to center-involving DME treated with intravitreal anti-VEGF injections between April 2007 and February 2017 were reviewed. The eyes were divided into mutually exclusive three groups based on the duration of follow-up (12, 24, or 36 months). Primary outcome measures were changes in visual acuity (VA) and central macular thickness (CMT) from baseline to final visit in each cohort, frequency of visits and intravitreal anti-VEGF injections. As secondary endpoints, VA outcomes were assessed in subgroups stratified by baseline VA [70 ETDRS letters and ≥70 ETDRS letters] and loading dose status of anti-VEGF injections.VA increased by a mean of 8.2 letters (12-month cohort, p 0.001), 5.3 letters (24-month cohort, p 0.001), and 4.4 letters (36-month cohort, p = 0.017) at final visits. The eyes with 70 VA letters achieved more significant VA improvement at final visits in all cohorts compared with eyes with 70 VA letters (p 0.001). The mean decreases in CMT from baseline to last visits at 12-, 24-, and 36- month cohorts were -100.5 µm, -107.7 µm, and -114.3 µm, respectively (p 0.001). The mean number of injections given were 4.6, 2.3, and 1.8 during years 1 to 3, respectively. Patients who received loading dose showed greater VA gains than those who did not in all follow-up cohorts.Our study revealed that anti-VEGF treatment improved VA and CMT over a follow-up of 36 months. Although these real-life VA outcomes following anti-VEGF therapy for DME were similar to other real-life studies, they were inferior to those noted in randomized controlled trials, mainly due to undertreatment.

Purpose Assess correlation between change in central subfield thickness (CST) and change in best-corrected visual acuity (BCVA) in eyes with macular edema due to retinal vein occlusion (RVO) that received intravitreal aflibercept injections (IAI). Methods Post hoc analysis of COPERNICUS and GALILEO trials for CRVO and VIBRANT trial for BRVO with relationships determined using Pearson correlation coefficient. Results In COPERNICUS, correlations (r) between change in CST and change in BCVA from baseline at weeks 12, 24, 52, and 100 were −0.36 (95% CI: −0.52, −0.18; P P P P P = 0.003). Similar findings were noted for GALILEO (r, −0.45 to −0.23) and VIBRANT (r, −0.36 to −0.32) trials. Conclusion In eyes treated with IAI for macular edema due to RVO, correlation between change in CST and change in BCVA was weak to moderate. While change in CST may be helpful in determining the need for anti-VEGF therapy, these findings do not support using changes in CST as a surrogate for changes in visual acuity outcomes.

Purpose To evaluate the relationship between retinal fluid location, amount/severity, and vision with ranibizumab-treated neovascular age-related macular degeneration (nAMD). Methods In the phase 3 HARBOR trial (NCT00891735), treatment-naive patients with nAMD received ranibizumab 0.5 or 2.0 mg through month 24. This post hoc analysis included eyes with subretinal fluid (SRF) and/or intraretinal fluid (IRF) at screening, baseline, or week 1, and optical coherence tomography data at months 12 and 24 (n = 917). Outcomes were best-corrected visual acuity (BCVA) change from baseline and proportion of eyes with 20/40 or better vision at months 12 and 24. Eyes were stratified by the location, amount, and/or severity of fluid. Results At baseline, 86% and 63% of eyes had SRF and IRF, respectively. Among eyes with residual SRF, mean BCVA gains at each time point were greater in eyes with central versus noncentral SRF; location did not affect the odds of having 20/40 or better vision over 24 months. Eyes with 20/40 or better BCVA at month 12 had significantly lower SRF thickness versus eyes with worse vision; however, no difference was apparent at month 24. Vision was comparatively worse in eyes with residual IRF at months 12 and 24; location and severity did not appear to affect this outcome. Conclusion Residual IRF was associated with worse vision outcomes, regardless of location/severity, whereas, despite continued treatment, residual SRF was not associated with worse vision outcome at 24 months, regardless of location/thickness. These data suggest complex relationships between residual fluid, severity, and vision.

Purpose Combined use of photodynamic therapy (PDT) with intravitreal anti-vascular endothelial growth factors (anti-VEGF) agents, such as ranibizumab (IVR) or aflibercept (IVA), has been shown to be effective for treating polypoidal choroidal vasculopathy (PCV). However, it is currently not well established which anti-VEGF agent provides superior outcomes for performing combination therapy. The present study compares the visual outcomes and re-treatment burden of combination therapy of PDT with either IVR or IVA in a European cohort of patients with PCV. Methods A retrospective analysis was done on PCV patients who had received combination therapy of PDT with either IVR or IVA. The demographic characteristics, visual outcome, and anti-VEGF re-treatment exposures were analysed and compared. Results A total of forty-four eyes (n = 11 male, 25%) were included in the analysis: 7 patients received IVR, 19 started with IVR but switched to IVA (IVS), and 18 received IVA, in combination with PDT. The BCVA improved in all three groups at 6-, 12-, 18-, 24-, 30-, and 36-month follow-ups after PDT, although the improvement was not statistically significant in the IVR group. The number of intravitreal anti-VEGF injections required/year after PDT was significantly fewer than before PDT. Significantly less eyes in the IVS group attained a good visual acuity of more than 70 ETDRS letters at the final visit. Conclusion Both IVR and IVA combined with PDT were effective treatments for the European cohort of patients with PCV. In eyes refractory to IVR, performing PDT promptly may be more beneficial than switching to IVA.

Purpose To report the safety and effectiveness of intravitreal aflibercept (IVT-AFL) for diabetic macular edema (DME) in the real-world clinical practice setting in Japan. Methods In this prospective, multicenter, observational, post-marketing surveillance, patients with DME newly receiving IVT-AFL were enrolled. During a 24-month follow-up, the primary outcome was the occurrence of safety events. Other pre-specified endpoints were effectiveness indicators, such as best-corrected visual acuity (BCVA), central retinal thickness, and injection frequency. Results In total, 646 patients administered at least one IVT-AFL injection were included in the safety analysis. During the follow-up period, adverse events occurred in 42 patients (6.50%), whereas adverse drug reactions occurred in 12 (1.86%). In the 12 patients who had adverse drug reactions, seven events occurred in seven patients within the first month of the most recent injection. In addition, 622 patients were included in the effectiveness analysis set. The number of injections over 24 months was 3.6 ± 3.0 (mean ± standard deviation [SD]). BCVA (logarithm of the minimum angle of resolution) was 0.437 ± 0.362 (mean ± SD) (n = 622) at baseline and 0.321 ± 0.348 (n = 177) after 24 months of treatment with IVT-AFL. Central retinal thickness was 440.8 ± 134.2 μm (mean ± SD) (n = 444) at baseline and 355.5 ± 126.4 μm (n = 140) at 24 months. Conclusion Routine administration of IVT-AFL for DME was not associated with new safety concerns, and BCVA outcomes were maintained over 24 months in the real-world setting. Nonetheless, patients in this real-world setting received fewer injections than those in clinical trials, suggesting that a margin for improvement exists in clinical practice. Trial registration ClinicalTrials.gov: NCT02425501.

Purpose To assess the clinical and retinal imaging features of patients in whom retinal vascular occlusion (VO) had developed in temporal associations with COVID-19 vaccination. Methods In this retrospective case series, all consecutive adult patients with new onset VO within 6 weeks of vaccination against COVID-19 were included in the study between May 1 and October 31, 2021. All patients had a systemic medical health assessment, full ophthalmic evaluation, and complete fundus imaging. Results Fifteen eyes of VO (14 patients) after COVID-19 vaccinations were identified. The median time between vaccination and symptoms onset was 14 days (range 7–42 days). The mean best-corrected visual acuity (BCVA) was 20/55 with a range of 20/20 to 20/200. Eleven of 15 eyes (73.3%) had visual acuity improvement after intravitreal treatment at 60–90 days (range, 45–105 days) from the presentation. Four of 5 cases without systemic risk factors for VO had a mean BCVA > 20/32 at presentation and > 20/25 at the latest evaluation. Between May 1 and October 31, 2021, a temporal association was found between the 15 reported cases and COVID-19 vaccination out of a total of 29 VO (p = 0.05). The incidence of VO was higher in the considered period compared to the equivalent 6-month period in 2019 (1.17% vs 0.52%, respectively; p = 0.0134). Conclusions Retinal vascular occlusion with different grades of severity are reported in temporal association with COVID-19 vaccination. The exact pathogenic mechanism needs to be further studied. No certain causal relationship can be established from this case series.

COVID-19 emerged in the end of 2019 and was declared a worldwide pandemic shortly after. Social distancing and lockdowns resulted in lower compliance in intravitreal injections and office visits. We aimed to assess clinical outcomes among patients who missed these visits compared to those who arrived as planned.Patients who missed or were late to office visits or intravitreal injections were defined as non-adherent and were compared to adherent patients. Our main outcomes were the need for subsequent injections, mean change in best-corrected visual acuity (BCVA), and central macular thickness (CMT).This study included 77 patients (24 adherent and 53 non-adherent). The mean BCVA remained stable during the study period for the adherent group (p = 0.159) and worsened in the non-adherent group (p 0.001). Changes in CMT and maximum thickness were not significant for either group. A higher proportion of patients in the non-adherent group needed subsequent intravitreal injections (49% vs 20%, p = 0.014).The findings demonstrate the negative implications of the COVID-19 pandemic and the effect of deferring bevacizumab injections among individuals with age-related macular degeneration. This emphasizes the importance of a scheduled follow-up, also during a pandemic.

Choroidal thickness (CT) plays an important role in the pathogenesis of various ocular diseases, including neovascular age-related macular degeneration (nAMD). Previous studies evaluated the CT variations after anti-vascular endothelial growth factor (VEGF) injections in patients with nAMD, but the results are still controversial. The present study aimed to evaluate the CT at different times (15, 30, 60, 90, and 365 days) after intravitreal aflibercept injections and its correlation with the baseline CT in treatment-naïve patients with nAMD. Secondly, the study evaluated the correlation between CT variation at 365 days and the number of intravitreal injections received.This was a prospective, open-label, single-arm pilot study. Twenty-one treatment-naïve nAMD eyes were enrolled. The study population underwent three monthly aflibercept injections (loading phase) and additional injections as needed (pro re nata regimen). A complete ophthalmological examination, including optical coherence tomography (OCT) was performed at each visit. CT was measured manually by two independent observers. All patients were evaluated at baseline and at 15, 30, 60, 90, and 365 days after the first intravitreal injection.CT showed a statistically significant reduction at days 15, 90, and 365 in comparison to baseline. However, the major reduction of CT was observed at day 15 and in eyes with a thicker choroid at baseline. No significant correlation between CT variation and the number of injections performed was found.Our findings contribute to clarifying the role of aflibercept injections in choroidal vasculature, confirming its effect after the first 2 weeks. Moreover, CT can be considered as a potential biomarker, as it reflects the pharmacological effect of anti-VEGF drugs.

To investigate short-term treatment outcomes of intravitreal brolucizumab (IVBr) for treatment-naïve neovascular age-related macular degeneration (AMD) in a Japanese multicenter study.Retrospective case control study METHODS: The subjects were 58 eyes of 57 patients with neovascular AMD (43 men and 14 women, mean age 74.6 years) of whom 43 eyes of 42 patients completed initial loading of 3 monthly IVBr injections and were followed for more than 3 months. Best-corrected visual acuity (BCVA) changes, anatomical outcomes, and complications were investigated.Of the 43 eyes that completed loading doses, the AMD subtype was type 1 and type 2 macular neovascularization (MNV) in 51%, polypoidal choroidal vasculopathy (PCV) in 42%, and type 3 MNV in 7%. At 3 months after initiating treatment, BCVA significantly improved (P = 0.002) and central retinal thickness significantly decreased (P 0.0001). At 3 months, complete retinal and subretinal fluid resolution was achieved in 91% of all eyes and complete regression of polypoidal lesions was achieved in 82% of PCV eyes. Iritis occurred in 8 eyes of 8 patients (14%), but resolved using topical or subtenon corticosteroid injection without visual loss in all cases.IVBr for treatment-naïve neovascular AMD was effective in the short-term, achieving significantly improved BCVA, good retinal fluid resolution, and a high rate of polypoidal lesion regression. However, iritis was noted in 14% of patients which may limit use of this drug.

Concomitant vitamin D deficiency (VDD) is speculated to aggravate diabetic macular edema (DME). We aimed to determine the effect of hypovitaminosis D correction on the outcome of treatment with intravitreal bevacizumab (IVB) in DME eyes.In this randomized clinical trial, 83 eyes of 83 patients with DME were recruited and divided into three groups: normal vitamin D levels + IVB administration (Group 1), vitamin D insufficient/deficient + IVB administration (Group 2), and vitamin D insufficient/deficient + IVB administration + oral vitamin D supplementation (Group 3). Participants were followed for 6 months after the intervention. Visual (corrected distance visual acuity, CDVA) and anatomical (central macular thickness, CMT) outcomes of intervention were evaluated 1, 3, and 6 months after three monthly loading doses of IVB were given. Serum vitamin D levels were measured 1 and 6 months after the third IVB administration.A total of 29, 26, and 28 eyes were enrolled in groups 1, 2, and 3, respectively. In months 1, 3, and 6, after the three basic loading doses of IVB, visual acuity and CMT improved in all three groups, but improvements (both functional and anatomical) in groups 1 and 3 in month 6 were more significant than in group 2 (mean CDVA LogMAR changes: - 0.18 ± 0.03, - 0.14 ± 0.05, and - 0.2 ± 0.06; mean CMT reductions: - 82.24 ± 11.43, - 66.62 ± 14.34, and - 86.14 ± 18.36, in groups 1, 2, and 3, respectively; p 0.001). The mean number of IVB injections during follow-up was 5.33 (range 4-7), which did not differ between the groups.Correction of vitamin D deficiency in DME patients with type 2 diabetes and vitamin D deficiency, in addition to IVB injections, may play a role in improving CDVA and CMT. However, this beneficial effect seems to be delayed by several months.Iranian Registry of Clinical Trials (IRCT), IRCT20200407046978N1, registered on April 11, 2020, retrospectively registered ( https://en.irct.ir/trial/46999 ).

To analyse the varied clinical profile and treatment outcomes of posterior zone 1 retinopathy of prematurity (ROP).This retrospective case-series included 54 eyes of 27 infants of posterior zone 1 ROP treated at our centre from January 2018 to June 2019. Three clinical patterns were observed at presentation - Posterior zone 1 ROP without detachment (group 1), with subtotal detachment (group 2) and total detachment (group 3) of the vascularised retina. Their profile, treatment options and outcomes were studied.The mean birth weight was 1204 ± 262 gm and mean gestational age was 28.8 ± 2 weeks. Clinical presentation as per group 1, 2 and 3 was seen in 33/54 (61.1%), 9/54 (16.6%) and 12/54 (22.2%) eyes, respectively. All the eyes received intravitreal ranibizumab as primary intervention. In group 1, 25/33 (75.7%) eyes had laser and 8/33 (24.2%) had surgery whereas, in group 2, 2/9 (22.2%) eyes had laser and 7/9 (77.7%) underwent surgery as a second intervention. In group 3, only 3 /12 (25%) eyes had second intervention (surgery). Surgical outcomes of group 1 and 2 were better than group 3. At last follow-up, macular vascularisation was noted in 33/54 (61.1%) eyes.A customised and multifaceted treatment approach is required to treat posterior zone 1 ROP.

To determine the outcome of Intravitreal Avastin (IVA) injections in patients with Macular Oedema (MO) in Uganda.We prospectively recruited patients presenting with MO at the Department of Ophthalmology of Mbarara University of Science and Technology in Southern Uganda from November 2018 to April 2019. We treated them with intravitreal injection of Bevacizumab (Avastin®) and followed them up for three consecutive months after the initial injection. We collected information on baseline clinical presentation and 3 month outcomes. We performed a Student's t-test to compare central macular thickness (CMT) and best corrected visual acuity (BCVA) at baseline and at 3 months after IVA injections. We performed linear regression to test for predictors of change in CMT and BCVA at 3 months.We enroled 32 patients (35 eyes) of which 29 patients (32 eyes) completed the follow up. The mean age was 62.8 ± 11.8 years, and 53% were male. At 3 months after IVA, the mean CMT improved significantly from 426.90 ± 135.9 µm at baseline to 311.20 ± 134.80 µm (p = 0.0008). The mean BCVA improved from 0.70 ± 0.38 at baseline to 0.38 ± 0.36 logMAR units (p = 0.003). The improvement in CMT and BCVA were more marked in patients who had Diabetic ME compared to other causes. A high baseline CMT was a strong predictor of improvement in CMT at 3 months after IVA therapy. A worse baseline visual acuity was a predictor of improvement in vision at 3 months after IVA.IVA therapy results in anatomical and visual improvement at 3 months especially in patients with Diabetic MO. Having a high baseline CMT was a predictor of good CMT outcome at 3 months while a worse vision at baseline was a predictor of better visual outcome at 3 months.

Purpose To verify the correct decision-making procedure on performing an intravitreal injection by investigating the in vivo wound morphology and evolution of 22-gauge wounds after dexamethasone oblique injection with anterior segment optical coherence tomography (OCT). Design Prospective, observational consecutive case series. Methods Subjects underwent a dexamethasone injection at University Eye Clinic of Turin. All the injections have been performed in an oblique (aka beveled or angled) fashion. Patients were divided according to the number of injections already performed with dexamethasone. Group 1 consisted of patients at the first injection, group 2 of patients at a second or more injection always in the same quadrant, and group 3 of patients at the second or more injection in a different quadrant. The incisions were imaged with the Heidelberg SPECTRALIS OCT device on postoperative days 1, 8, and 15. The main outcome measure was wound structure/characteristics (e.g., presence of gaping) as evaluated with OCT. Surgical and ocular parameters were also recorded. Results Thirty-three consecutive patients were investigated. OCT demonstrated closed wounds in all eyes on postoperative days 1, 8, and 15. In all patients, the external (entry) side of the incision was seen as a gape; however, the rest of the wound was closed. No complications were recorded in the different patients during the follow-up. In patients of group 1, we identified the scleral pathway in 10 eyes at day 1. At 8 days in 9 of 10 eyes, the sclera had returned to its restitutio ad integrum. In patients of group 2, the scleral pathway was recognizable on the first day of control; in 7 patients, this was accompanied by the presence of intrascleral edema with peri-wound fluid. At the 8-day checkup, 3 eyes still showed signs attributable to the intrascleral pathway accompanied by peri-wound edema. In group 3, it was possible to identify the intrascleral pathway in 8 patients. There were no signs of intrascleral peri-wound edema or other anatomical changes in 9 patients as early as the first day. In the 8-day follow-up, the signs of scleral edema were absent in the single patient who presented them. At 15 days, there were no signs of scleral pathway in all eyes analyzed. Conclusions Speaking of intravitreal injections of slow-release dexamethasone, the technique that involves moving the conjunctiva and a beveled or angled sclerotomy after a careful choice of the injection site, paying attention to vary the quadrant involved with each puncture, reduces the number of days of closure of the sclera via and the scleral damage, thus protecting the patient from complications. For the future, it is hoped that the operating microscope and intraoperative OCT will be used on every occasion.

To investigate the predictors of annual treatment frequency in the second year of pro re nata (PRN) intravitreal ranibizumab (IVR) injections for diabetic macular edema (DME).A retrospective study.We reviewed 65 eyes of 60 patients with center-involved DME who received PRN IVR injections after 3 monthly loading doses. The central subfield thickness (CST) and qualitative findings were assessed on the spectral domain optical coherence tomography (SD-OCT) images. We then investigated whether the parameters at the baseline or at the 12-month visit were associated with treatment frequency in the second year.The number of ranibizumab injections decreased from 6 (4-8) during the first year to 2 (0-3) during the second year (P.001). The injection numbers during the first year (ρ = 0.259, P = .037) but not during the second year (ρ = 0.152, P = .226) were modestly related to the logarithm of the minimum angle of resolution (logMAR) improvement at 24 months. Multivariate analyses revealed that the CST (β = 0.336, P = .005) and hyperreflective walls in the foveal cystoid spaces (β = 0.273, P = .020) at baseline were associated with the number of IVR injections during the second year. The treatment frequency during the second year was also related to the CST (β = 0.266, P = .012), hyperreflective walls (β = 0.394, P = .002), and cumulative doses of ranibizumab injections (β = 0.294, P = .006) at the 12-month visit.The cumulative doses of ranibizumab injections, CST, and hyperreflective walls in the foveal cystoid spaces at the 12-month visit are designated predictors of the treatment frequency of ranibizumab injections during the second year in DME.

To evaluate the retinal vascularization of repeated intravitreal ranibizumab (IVR) for reactivated retinopathy of prematurity (ROP) treated with IVR monotherapy.The retrospective study reviewed ROP infants who accepted IVR injection as the first treatment in our department from January 2017 to December 2018. The ratio of the distance from the center of the optic disc to the border of the vascularized zone (DB) to the distance from the center of the disc to the fovea (DF) was used for the vascular outgrowth analysis.Seventy-eight infants were included in the study. A total of 54.3% of the reactivated ROP patients could achieve complete vascularization after repeated IVR injections. Gestational age (GA) 29 weeks and a temporal DB/DF ratio ≥ 3 in the first IVR were potential predictors for complete retinal vascularization after IVR monotherapy. The temporal DB/DF ratio ≥ 3.6 in the second IVR injection was a potential predictor for complete retinal vascularization after repeated IVR for ROP reactivation.Reactivated ROP after IVR monotherapy can be treated successfully with repeated IVR injections. GA and temporal DB/DF ratio are potential predictors of complete retinal vascularization in ROP infants treated with IVR.

INTRODUCTION The purpose was to compare two flexible regimens of intravitreal aflibercept (IVT-AFL) with fixed dosing every 8 weeks, beyond the first year of treatment, in patients with diabetic macular edema (DME). VIOLET was a 100-week, randomized, Phase IIIb, non-inferiority study in patients with center-involving DME previously treated with IVT-AFL for ≥ 1 year according to the European label. METHODS Patients received an initial dose of IVT-AFL at study baseline and were randomly assigned (1:1:1) to treat-and-extend (T&E), pro re nata (PRN), or fixed regimens. The primary endpoint was mean change in best-corrected visual acuity (BCVA) from baseline (randomization) to Week 52. RESULTS Full analysis set comprised 458 patients (baseline mean BCVA: 72.5, 71.0, and 72.7 letters in the T&E, PRN, and fixed-dose groups, respectively). Patients received a mean (min-max) of 10.0 (2-14; T&E), 11.5 (1-25; PRN), and 12.3 (3-13; fixed) injections over 100 weeks, with 13.3 (4-23), 25.0 (3-29), and 16.1 (5-25) clinic visits, respectively. At Week 52, mean (± standard deviation) BCVA changes from baseline were + 0.5 ± 6.7 (T&E), + 1.7 ± 6.8 (PRN), and + 0.4 ± 6.7 (fixed-dosing) letters (least squares mean difference [95% confidence interval]: T&E 0.01 [- 1.46, 1.47] and PRN 0.95 (- 0.52, 2.42) letters versus fixed dosing; p

Untreated neovascular age-related macular degeneration (nAMD) can lead to severe and permanent visual impairment. The chronic nature of the disease can have a significant impact on patients' quality of life and an economic and time burden on medical retina (MR) services, with the care need outweighing the growth of resources that clinical services can access. The introduction of a new treatment into clinical services can be challenging, especially for services that are already under capacity constraints. Guidance for practical implementation is therefore helpful. Roundtable meetings, facilitated by Novartis UK, between a working group of MR experts with experience of leading and managing NHS retinal services in the intravitreal era were conducted between 2020 and 2021. These meetings explored various aspects and challenges of introducing a new anti-vascular endothelial growth factor (VEGF) therapy to the UK medical retina services. Provision of clear expert recommendations and practical guidance nationally, that can be adapted locally as required to support clinicians and healthcare professionals (HCPs), is valuable in supporting the introduction of a new anti-VEGF therapy within the NHS environment. The experts provide ophthalmologic HCPs with a collation of insights and recommendations to support the introduction and delivery of brolucizumab in their local service in the face of current and projected growth in demand for retina care.摘要: 未经治疗的新生血管年龄相关性黄斑变性(nAMD)可导致严重永久性的视力损害。该疾病的慢性进展性的临床特征会对患者的生活质量产生重大影响, 并对视网膜疾病的服务造成经济方面和时间方面的负担, 其护理需求超过了临床服务目前可获得的资源增速。在临床服务中引入一种新的治疗方法可能具有挑战性, 特别是对于已经受到限制的服务而言。因此, 对临床实践进行指导是非常有益的。在诺华英国公司的协助下, MR专家工作组在2020年至2021年期间召开了圆桌会议, 这些专家拥有在玻璃体腔注药时代领导和管理NHS视网膜服务的丰富经验。这些会议探讨了将一种新的抗血管内皮生长因子(VEGF)引入英国医疗视网膜服务的各个方面的问题和挑战。为了支持临床医生和医疗保健专业人员(healthcare professionals, HCPs), 对在全国范围内提供的明确的专家建议和实用指南, 可以根据需要在当地进行调整, 这对于支持在NHS环境中引入新的抗VEGF疗法非常有价值。面对当前和预计的视网膜护理需求增长, 专家们为眼科医务人员提供了一系列见解和建议, 以支持在他们的本地服务中引入和使用布洛赛珠单抗。.

Myotonic dystrophy type 1 (DM1) is an autosomal dominant genetic disorder that affects multiple organs, including the muscle and eye, caused by a CTG triplet expansion of the 3' untranslated region (UTR) of the DMPK gene. Cataracts and retinal degeneration are major eye complications in patients with DM1. We reported the case of a Japanese patient with DM1 who exhibited submacular hemorrhage unilaterally, rarely complicating DM1.A 56-year-old woman presented with loss of visual acuity in the left eye (LE). The patient was diagnosed with DM1, who carried expanded CTG repeats (1100) of the 3' UTR of DMPK. Her corrected visual acuities were 20/100 and 20/2000 in the right eye (RE) and LE, respectively. Cataracts were observed in both eyes. Fundoscopy and angiography revealed submacular hemorrhage in the LE due to polypoidal choroidal vasculopathy (PCV, also known as aneurysmal type 1 neovascularization). The patient underwent intravitreal injections of an anti-vascular endothelial growth factor drug and sulfur hexafluoride gas in the LE. Full-field electroretinography was performed, showing that the rod and standard-flash responses were reduced to 50% and below 10% in the RE and LE, whereas the cone and 30-Hz flicker responses were reduced to 40-50% and 15-20% in the RE and LE, respectively, compared with the controls. Multifocal electroretinography revealed that the overall responses were extinguished in the LE and considerably attenuated in the RE.This is the first patient with DM1 complicated with PCV. Widespread retinal dysfunction may be associated with expanded CTG repeats, which is significantly longer than the mean repeat number of patients with DM1.

To examine the 16-week outcomes of switching to brolucizumab in eyes with neovascular age-related macular degeneration (nAMD) refractory to aflibercept.Retrospective observational study.Data of eyes with nAMD who switched to brolucizumab because of resistance to aflibercept were collected. The best-corrected visual acuity (BCVA; in logarithm of the minimum angle of resolution), central retinal thickness (CRT), central choroidal thickness (CCT), and exudative status on optical coherence tomography were analyzed.A total of 48 eyes of 48 patients were reviewed. At 4 to 7 weeks after switching, BCVA changed from 0.26 ± 0.19 to 0.25 ± 0.21 (not significant; P = 0.95), but CRT significantly decreased from 298.9 ± 108.4 µm to 241.9 ± 92.5 µm (P 0.001) and CCT from 182.6 ± 89.3 µm to 169.7 ± 82.6 µm (P 0.001). Of the 23 eyes refractory to monthly aflibercept injections, 12 (52.2%) achieved a dry macula, and 8 (34.8%) reduced exudative changes at 1 month. At 16 weeks, 31 eyes (64.6%) achieved the treatment interval ≥ 8 weeks. Two patients (4.2%) dropped out, 7 eyes (14.6%) developed intraocular inflammation (IOI), and 8 eyes (16.7%) switched back to aflibercept because of the failure to extend the treatment interval ≥ 8 weeks.Switching to brolucizumab in eyes refractory to aflibercept conferred favorable outcomes in controlling exudative changes. However, IOI and the regulation of the treatment interval to at least 8 weeks during the maintenance phase disrupted the continuation of brolucizumab treatment.

Purpose To evaluate the outcome of pneumatic vitreolysis (PVL) for vitreomacular traction (VMT) with or without full thickness macular hole (MH) Methods Forty-seven eyes of 47 patients were included who had undergone PVL for VMT with or without MH. Main outcome measures were release of VMT, MH closure, best-corrected visual acuity (BCVA) and adverse events. Results Thirty-three patients had isolated VMT and 14 patients VMT with a MH. Four weeks after PVL, the overall VMT release rate was 35/47 (74.5%): 25/37 (67.6%) in phakic and 10/10 (100%) in pseudophakic eyes (p = 0.03). Four of 14 MH (28.6%) were closed. Twenty-two of 47 (46.8%) eyes required a subsequent PPV: 12/33 (36.4%) in the VMT only group and 10/14 (71.4%) in the VMT with MH group. Mean BCVA improved from 0.48 (± 0.24) to 0.34 (± 0.23) logMAR at 6 months in patients with VMT alone (p p = 0.008). Adverse events included new formation of a large MH in 4/33 (12.1%) eyes, failure of MH closure in 10/14 (71.4%) eyes, progression of mean minimum linear diameter (MLD) MH size from baseline 139 (± 67) to 396 (± 130) µm (p Conclusion While PVL leads to a high VMT release rate particularly in pseudophakic eyes, it is associated with a relatively high incidence of MH formation, MH size progression and retinal detachment.

Purpose To investigate the outcomes of a suspension of anti-vascular endothelial growth factor (anti-VEGF) treatments in the eyes with neovascular age-related macular degeneration (nAMD). Methods This was a retrospective study that examined eyes having no exudation for 48 weeks while undergoing intravitreal anti-VEGF injections every 12 to 16 weeks. The rate and time of recurrences, best-corrected visual acuity (BCVA), central subfield thickness (CST), number of visits, and reactivity to anti-VEGF were determined after the suspension of the anti-VEGF treatments. Results In 34 eyes of 34 patients, 17 eyes (50.0%) had a recurrence during the 24-month follow-up period. The median time of a recurrence was 10 months. The BCVA was maintained for 24 months after the suspension regardless of the development of any recurrences. In 41.7% of the eyes that resumed treatment, the duration of exudation suppression by the anti-VEGF therapy was shorter than 12 weeks during the 12 months after restarting the anti-VEGF treatments. There was a significant increase in the number of visits during the first year after beginning the suspension versus during the 1 year before the suspension (non-recurrence group; P = 0.007, recurrence group; P = 0.001). Conclusion Although one-half of the eyes had a recurrence within 24 months after a suspension of anti-VEGF treatment, the BCVA was maintained after a resumption of the anti-VEGF treatments. However, the number of hospital visits increases regardless of the recurrences and the lesion stability is altered by the anti-VEGF suspension. Clinicians should explain both the advantages and disadvantages of anti-VEGF suspension to nAMD patients.

Purpose To compare the efficacy and refractive outcomes of intravitreal bevacizumab, ranibizumab and aflibercept in retinopathy of prematurity (ROP) treatment. Methods We analyzed the files of patients treated with intravitreal bevacizumab, ranibizumab and aflibercept for ROP, retrospectively. A total of 187 eyes of 111 patients were included. Recurrence time after initial treatment, recurrence rate, age and rate of additional treatment, refractive outcomes in age 1, 2 and 3 were evaluated and compared between the groups. Results Fifty-four eyes of 30 patients formed bevacizumab group (Group-1), 77 eyes of 47 patients formed ranibizumab group (Group-2) and 56 eyes of 34 patients formed aflibercept group (Group-3). No significant difference was found in gender, gestational age, birth weight and risk factors between the groups (p>0.05). Success rate was higher in group 3, but the difference was not significant (p = 0.174) (74.1% in group-1, 62.4% in group-2 and 76.8% in group-3). Recurrence rate was higher in group 2, but the difference was not significant (p = 0.158) (25.9% in group-1, 37.6% in group-2 and 23.2% in group-3). Recurrence time after initial treatment was significantly shorter in group 2 (p < 0.01). Additional treatment rate was also higher, and the age of additional treatment was lower in group-2 (p < 0.05 and p < 0.01, respectively). We found refractive values more myopic in ages of 1, 2 and 3 in group 1. Conclusions Bevacizumab, ranibizumab and aflibercept are effective treatment alternatives for ROP. We observed more frequent and much earlier recurrence in eyes treated with ranibizumab. A myopic shift was found in bevacizumab group. We also emphasize the necessity of longer follow-ups for infants treated with anti-VEGF drugs.

Introduction Switching to an alternative anti-vascular endothelial growth factor (anti-VEGF) agent has been suggested for patients with neovascular age-related macular degeneration (nAMD) who have a suboptimal response to initial therapy. However, post hoc analyses of some studies have shown that continuation of initial anti-VEGF therapy is, in many cases, associated with stable visual outcomes or gradual gains. Methods This ARIES (ClinicalTrials.gov Identifier: NCT02581891) post hoc analysis describes outcomes in patients with treatment-naïve nAMD receiving treat-and-extend intravitreal aflibercept (IVT-AFL) for 104 weeks, who were identified as meeting criteria for an early hypothetical switch. Patients were categorized retrospectively according to six criteria (presence of central intraretinal and/or subretinal fluid at week 8 or 24, with/without a next planned treatment interval ≤ 8 weeks, and with/without gains in best-corrected visual acuity [BCVA] ≤ 5 letters [with absolute BCVA

This study aimed to evaluate the one-year outcomes of photodynamic therapy (PDT) as a rescue treatment for age-related macular degeneration (AMD) refractory to anti-vascular endothelial growth factor (VEGF) therapy.Patients with AMD refractory to anti-VEGF therapy, treated with "rescue-PDT" were retrospectively investigated. The time of PDT was defined as the baseline value. Baseline characteristics including sex, age, best-corrected visual acuity (BCVA), central macular thickness (CMT), and foveal choroidal thickness (FCT) were examined. The changes in BCVA, CMT, and recurrence were also assessed at the 1-year follow-up. The logMAR VA change of 0.3 or more was defined as "improved" or "declined."Twenty-three consecutive eyes (typical AMD: 10 eyes, polypoidal choroidal vasculopathy: 10 eyes, and pachychoroid neovasculopathy: 3 eyes), which underwent "rescue-PDT," were analyzed in this study. The BCVA was improved in three patients and maintained in 20 patients at 12 months after PDT (mean BCVA change: 0.11 ± 0.19). The CMT improved in 19 patients (82.6%), and the mean CMT changed from 318.5 ± 93.7 μm to 225.9 ± 51.6 μm (p 0.01) 12 months after PDT. "Retreatment" of anti-VEGF drug injections was considered if the retinal fluid or retinal hemorrhage recurred after PDT. The baseline FCT of the "retreatment group (15 eyes)" was significantly lower than that of the "no retreatment group (8 eyes)" (206.3 ± 50.7 μm vs 293.9 ± 85.7 μm: p = 0.033).PDT could be an effective treatment option for anti-VEGF refractory AMD to maintain visual acuity and control retinal fluid for up to 12 months.

Introduction To evaluate the effects of combined therapy using intravitreal Aflibercept (IVA) and photodynamic therapy (PDT) on polypoidal choroidal vasculopathy related to pachychoroid disease (PPCV).Methods Patients with PPCV were treated with PDT combined with 3 IVA injections on a monthly basis, followed by pro re nata criteria. The 12-month follow-up consisted of multiple revaluations of visual acuity and SSOCT parameters of clinical activity.Results Nineteen eyes were included in the study; mean age was 65.5 years. Visual acuity improved after 12 months (0.35 ± 0.25 to 0.2 ± 0.20 logMAR, p = 0.005). Percentage of eyes with intraretinal and subretinal fluid reduced from baseline to the 12-month follow-up (from 52.6–10.5%, p = 0.12, and from 89.5–5.3% p = 0.0009, respectively). Central retinal and mean macular thicknesses reduced (258 ± 39.6 to 204.8 ± 38.8 µm p = 0.04 and 293.8 ± 32.1 to 248.1 ± 29.6 µm p = 0.017 respectively). Central choroidal and mean choroidal thicknesses also displayed a reduction (328.6 ± 54.9 to 289.8 ± 44.6 µm p = 0.001 and 314.5 ± 55.3 to 287.9 ± 47.6 µm p = 0.015 respectively). The mean number of injections was 4.6/year.Conclusion The results support the use of a combined therapy with Aflibercept and PDT in PPCV. This treatment would act in synergy, with anti-VEGF controlling exudation and PDT closing the aneurysmal vessel and reducing choroidal congestion.

Purpose This study aims to evaluate the impact of the first coronavirus 2019 (COVID-19) wave in 2020 on patients scheduled for intravitreal injections (IVI) in a German metropolitan region. Methods We performed a multicentre prospective survey and retrospective analysis of the records of patients treated with intravitreal injections during the 20-week period from March to July 2020 in all four hospital eye departments in the city of Hamburg using a questionnaire (on treatment adherence, SarsCoV2-related personal, familial and social data) and treatment data. Results A total of 1038 patients (2472 IVI, 1231 eyes) and 818 questionnaires were evaluated. Longer duration of therapy, lower visual acuity (VA) of the treated and higher VA of the fellow untreated eye was were associated with a higher probability of visit cancellation. Every additional year of life posed a 2.6% lower risk of noncompliance. A COVID-19 infection in the family environment displayed a 5.5-fold chance of visit cancellation. Patients treated for neovascular age-related macular degeneration (nAMD) had a 36% reduced risk of visit cancellation compared to patients with diabetic macular oedema (DME). Conclusion A long preceding treatment period, low VA of the treated eye, high VA of the untreated eye, COVID-19 in the family and DME were identified as risk factors for IVI visit cancellations during the COVID-19 pandemic. Compliance to treatment might be improved in the future by taking these risk factors into account when scheduling patients for IVI during the exceptional circumstances of a pandemic.

Purpose To evaluate the efficiency of low-dose intravitreal ranibizumab therapy in the treatment of aggressive retinopathy of prematurity (A-ROP). Methods A total of 124 eyes of 62 patients who underwent intravitreal ranibizumab after an A-ROP diagnosis between January 2015 and January 2021 were evaluated retrospectively. After receiving family-approved informed consent, low-dose intravitreal ranibizumab was administered, and regular follow-ups were performed. Results Patients included in the study had a mean birth week of 26.6 (23-33 weeks), a mean birth weight of 905 (450-1970) grams, and an average injection postnatal time of 9.1 (4-19) weeks. The mean follow-up period was 63 (24-250) weeks. In all eyes, ROP regressed in the first week after injection, and no asymmetrical response was observed in the eyes of any baby. A total of 58 eyes recovered with a single dose of intravitreal injection therapy, and peripheral retinal vascularization was completed. A second injection was required in 38 eyes. Rescue treatment was applied in addition to intravitreal ranibizumab treatment in 22 eyes of 11 babies. None of the patients had any ocular or systemic side effects. Conclusion Low-dose intravitreal ranibizumab injection with close follow-up and appropriate timing is an effective treatment modality in A-ROP. Even among patients undergoing rescue laser treatment, the treatment can be completed with a wide visual field.

This study compared pain and anxiety levels in individuals receiving intravitreal injections (IVIs) using a speculum-free injection technique, the lid splinting eyelid retraction technique, or using a speculum.This was a prospective study of individuals receiving IVI at a single tertiary care medical center who responded to a questionnaire and visual analog scale (VAS) between December 2019 and January 2020. In one group, a speculum was used prior to injection, whereas in the other group, a speculum-free injection technique was used.A total of 108 individuals were included in this study: 54 received IVI with the speculum-free lid splinting eyelid retraction technique and 54 received IVI with a speculum. A correlation between pain and anxiety was demonstrated in the control group (p-value 0.01); however, in the speculum-free group, this correlation was lower and not significant. When comparing pain and anxiety between the study groups, lower median pain (Mood's: Z = 5.378, p-value 0.001) and lower anxiety (Mood's: Z = 2.108, p-value = 0.035) scores were demonstrated in the speculum-free group than in the control group. The distribution of pain scores was significantly different between the study groups (Kolmogorov-Smirnov: D = 0.518, p-value 0.001), and trending differences in anxiety between the groups were observed (Kolmogorov-Smirnov: D = 0.259, p-value = 0.053).The lid splinting eyelid retraction technique, a speculum-free technique, was associated with less anxiety and pain in patients than the use of a speculum. As IVI often involves repeated treatment, identifying modifiable factors that may relieve anxiety and pain is of utmost importance.

This study aims to evaluate the outcomes of adalimumab (ADA) therapy in patients with refractory punctate inner choroidopathy (PIC) and multifocal choroiditis (MFC).Demographic and clinical data, including LogMAR best-corrected visual acuity (BCVA), were retrospectively collected. Doses of prednisone, immunomodulatory therapies (IMT), and anti-vascular endothelial growth factor (VEGF) injections before and after baseline (ADA initiation) were recorded, as well as the time to clinical remission, time to first flare, and drug-associated adverse events.Seven patients (4 females, ten eyes) were included. The mean follow-up after baseline was 17.8 ± 11.1 months (range 6-33). The mean LogMAR BCVA was 0.35 ± 0.77 at 6 months before baseline and remained stable throughout 12 months after baseline (0.31 ± 0.46 at 12 months; p = 0.47). The mean dose of prednisone decreased from 17.3 ± 19.6 mg/day 6 months before baseline (range 0-60) to 2.6 ± 2.4 mg/day at the last follow-up (range 0-6, p = 0.03). The mean number of flares decreased significantly from 1.43 ± 0.79 over a 6-month period before baseline to 0.2 ± 0.45 (p = 0.02) at 6-12 months after baseline. The mean number of anti-VEGF injections was 4.17 ± 3.92 over the 12-month period before baseline, and it was 2.17 ± 3.06 (p = 0.31) during the first 12 months after baseline. No adalimumab-related adverse events were noted.Adalimumab therapy for refractory PIC/MFC enabled a significant steroid-sparing effect, decreased disease flares, and preserved vision over a mean follow-up of 17.8 months.

To evaluate the changes in choriocapillaris (CC)/Sattler and Haller layer thicknesses in eyes with neovascular age-related macular degeneration (nAMD) after aflibercept or ranibizumab injections.Retrospective.A total of 70 eyes of 70 patients with treatment-naïve exudative nAMD were treated with 3 consecutive injections of aflibercept (IVA) or ranibizumab (IVR). CC/Sattler and Haller layer thicknesses were measured at the nasal and temporal regions 1000 µm from the center of the fovea by enhanced-depth imaging optical coherence tomography at baseline and after the 3 monthly intravitreal injections. In addition, the hyperfluorescence region (HF) was measured as the largest horizontal diameter of the hyperfluorescence area on the early-middle phase fluorescein angiographic images at baseline and after the 3 loading doses.After the 3 consecutive injections, the mean reductions in the nasal/temporal CC/Sattler layer thicknesses in the IVR and IVA groups were - 10.1 ± 2.3/ - 8.5 ± 1.8 and - 25.2 ± 15.2/ - 19.4 ± 12.8 μm, respectively. Also, the mean reductions in the nasal/temporal Haller layer thicknesses in the IVR and IVA groups were - 6.5 ± 3.6/ - 7.2 ± 7.9 and - 9.5 ± 8.0/ - 7.0 ± 6.2 μm, respectively. The changes in the CC/Sattler layer thicknesses of the IVA group were greater than those of the IVR group (P .001); however, the changes in the Haller layer thickness were similar between the groups (P .05). The mean decrease in the HF size of the IVA group was greater than that of the IVR group (P .001).Aflibercept treatment has a more pronounced effect on the CC/Sattler layer. Such results may indicate that aflibercept treatment influences choroidal neovascularization, possibly by reducing the capillary permeability associated with active neovascularization in the CC layer.

To evaluate the effectiveness and safety of the dexamethasone intravitreal implant (DEX-I) in Non-Infectious Uveitis (NIU) in Chinese patients.Ninety-one eyes of 77 patients (56 men, 21 women) receiving 130 implant injections for NIU were included. Treatment indication, uveitis diagnosis, best-corrected visual acuity (BCVA), central retinal thickness (CRT), vitreous haze score, intraocular pressure, phakic status, number of injections, time to reinjection, and systemic treatments were collected at baseline, 1 week, 1 month, 3 and 6 months after treatment.All patients were followed for at least 12 weeks and had a mean follow-up period of 5.1 months (range, 3-14 months) after the first implant. The main treatment indications were macular edema (ME), retinal vasculitis, retinal vasculitis with ME. Sixty-one eyes (67.03%) received only one injection, while 31 eyes (32.97%) received two or more. In eyes that received 2 injections, the mean time to the second injection was 3.83 months and in those that received 3 injections, the mean time to the third injection was 7.5 months. BCVA and CRT significantly improved at 1 week, 1 month, 3 months, and 6 months after treatment. When compared to baseline, the mean prednisone (or equivalent) dosage significantly decreased at 3- and 6-month follow-up evaluations after DEX implantation.14.29% of eyes developed a transient increase in intraocular pressure, and a cataract was removed from 1 phakic eye.DEX implants, either alone or in combination with common adjunctive NIU treatments, is safe and effective in the treatment of NIU in Chinese patients.

To evaluate the difference between the incidences of sterile endophthalmitis after administration of intravitreal aflibercept injection using two different types of syringes.We administered a total of 498 intravitreal aflibercept injections between September 2017 and August 2021. The disposable syringe used was changed from a 1-mL disposable syringe (Profi syringe, Shinchang Medical., Ltd. Korea) to a 1-mL Becton Dickenson Luer-Lok syringe (BD, Franklin, NJ, USA) in September 2019. Thus, the patients who received injections before and after September 1, 2019, were classified into group 1 and group 2, respectively. The incidence of aflibercept-related sterile endophthalmitis between the two groups was compared.In group 1, six (2.791%) out of 215 cases were diagnosed with sterile endophthalmitis and prescribed topical or oral steroids. In group 2, one (0.353%) out of 283 cases was diagnosed with sterile endophthalmitis and prescribed a steroid eye drop. The incidence of sterile endophthalmitis was significantly different between the two groups (P = 0.046).The BD Luer-Lok syringe is associated with a lower incidence of aflibercept-related sterile endophthalmitis than the conventional polypropylene syringe. Differences in immunogenicity associated with silicone oil lubricants within the syringes might be one of the potential reasons behind the difference in the incidence of the sterile endophthalmitis.

BACKGROUND/OBJECTIVES This meta-analysis investigates the efficacy and safety of intravitreal anti-VEGF injections (IVI) compared to combination laser photocoagulation and IVI (LPC-IVI) in treating macular oedema secondary to retinal vein occlusion (RVO). SUBJECTS/METHODS A literature search of MEDLINE, EMBASE and Cochrane CENTRAL was conducted from inception until March 2021. Randomized controlled trials that reported relevant efficacy and/or safety parameters following LPC-IVI relative to IVI were included. Meta-analysis was conducted with a random effects model. The primary outcome was best-corrected visual acuity (BCVA), while secondary outcomes were central macular thickness (CMT), central retinal thickness (CRT), central subfield thickness (CST), number of IVIs received, and incidence of adverse events. RESULTS A total of 10 studies were included, for which 362 eyes were randomized to LPC-IVI and 365 to IVI. In comparing macular laser photocoagulation with IVI (MLP-IVI) in BRVO patients, no significant differences were seen in final BCVA (p = 0.78) or change in BCVA (p = 0.09) after treatment. Similarly, no significant differences were seen in final CMT (p = 0.54), change in CMT (p = 0.33), final CRT (p = 0.90), change in CRT (p = 0.97), or number of injections required (p = 0.78). The same results were seen in subgroup analyses for macular laser without peripheral laser in BRVO and CRVO patients. Consistent results were observed when considering peripheral LPC-IVI to IVI in BRVO and CRVO. CONCLUSIONS No significant differences were seen between combination MLP-IVI or peripheral LPC-IVI relative to IVI monotherapy for final BCVA or OCT parameters in macular oedema secondary to RVO.

OBJECTIVES For patients with polypoidal choroidal vasculopathy (PCV), intravitreal anti-vascular endothelial growth factor (anti-VEGF) combination therapy has been shown to be cost-saving relative to monotherapy in a clinical trial setting. However, whether this also applies to real-world settings is unclear. We aim to compare the real-world functional outcomes and cost-effectiveness of intravitreal anti-VEGF combination therapy relative to monotherapy, to investigate whether combination therapy is truly cost-saving. METHODS We used a Markov model to simulate a hypothetical cohort of PCV patients treated at Singapore National Eye Centre. Model parameters were informed by coarsened exact matched estimates of a two-year retrospective study of patients who initiated treatment in 2015. Treatment options included intravitreal aflibercept, bevacizumab, or ranibizumab, as monotherapy or in combination with full-fluence verteporfin photodynamic therapy. RESULTS The two-year logMAR letters gains were significant for combination therapy ( + 10.6, P = 0.006) but not monotherapy (-2.2, P = 0.459). Over 20 years, a PCV patient would cost the health system SGD 48,790 under monotherapy and SGD 61,020 under combination therapy. Quality-adjusted life-years (QALYs) were estimated to be 7.41 for monotherapy and 7.80 for combination therapy. The incremental cost-effectiveness ratio of combination therapy was SGD 31,460/QALY, which is less than the common willingness-to-pay threshold of per capita gross domestic product of Singapore (SGD 88,990/QALY). Sensitivity analysis showed that combination therapy remained incrementally cost-effective, but not cost-saving. CONCLUSIONS Our study shows that combination therapy is good value for money but is likely to increase costs when applied in real-world settings.

Aims To report the effect of simultaneous intravitreal dexamethasone (DEX) and aflibercept for the treatment of diabetic macular edema (DME). Methods This retrospective analysis of an open-label, multicenter, consecutive case series included 102 eyes of 81 patients with DME. Patients were selected into two groups. The control group consisted of 50 eyes treated with aflibercept alone, and the combination group consisted of 52 eyes treated with simultaneous DEX implant and aflibercept injection. The primary endpoints were changes in best-corrected visual acuity (BCVA) and central retinal thickness (CRT) from baseline to month 6. The secondary endpoint was the interval of retreatment. Results Baseline BCVA increased and CRT decreased at 6 months in both groups. Pseudophakic eyes in the combination group exhibited significantly greater BCVA improvement compared with phakic eyes (p = 0.031). Fewer intravitreal treatments were required for eyes treated with combination therapy than for those treated with aflibercept alone (1.56 ± 0.54 vs. 4.04 ± 1.26, p

To identify the eyes with macular edema (ME) due to a branch retinal vein occlusion (BRVO) that have good visual acuity during the continuous anti-vascular endothelial growth factor (anti-VEGF) treatment based on the patients’ clinical information and optical coherence tomography (OCT) images by using machine learning. Sixty-six eyes of 66 patients received 1 anti-VEGF injection followed by repeated injections in the pro re nata (PRN) regimen for 12 months. The patients were divided into two groups: those with and those without good vision during the 1-year experimental period. Handcraft features were defined from the OCT images at the time of the first resolution of the ME. Variables with a significant difference between the groups were used as explanatory variables. A classifier was created with handcrafted features based on a support vector machine (SVM) that adjusted parameters for increasing maximal precision. The age, best-corrected visual acuity (BCVA) at the baseline, BCVA at the first resolution of the ME, integrity and reflectivity of the external limiting membrane (ELM), the ellipsoid zone (EZ), and area of the outer segments of the photoreceptors were selected as explanatory variables. The classification performance was 0.806 for accuracy, 0.768 for precision, 0.772 for recall, and 0.752 for the F-measure. The use of the SVM of the patient’s clinical information and OCT images can be helpful for determining the prognosis of the BCVA during continued pro re nata anti-VEGF treatment in eyes with ME associated with BRVO.

Background The primary aim was to investigate outcome of the decision making on duration of injection intervals between injection visits over the first 2 years of a treat and extend regimen. Method Consecutive patients receiving Aflibercept for treatment naive neovascular age-related macular degeneration between 01.01.2016 and 15.07.2017 were identified from our departmental register. Retrospective data collected on all visits over 24 months were classified into three groups: (A) Without Interval Decision Events (IDE)" Injection only" (B) IDE resulting in injection intervals of 5 weeks. The primary outcome was number of successful IDE relative to the total visits in Group C. Successful decision making was defined as absence of worsening of visual acuity (>5 L) or central retinal thickness (>50 microns) at the subsequent visit. Secondary visual and anatomical outcomes at 24 months were also evaluated. Results Data from 56 eyes of 50 patients were included in the study. Visual acuity improved by +7.11 L at 24 months. Forty one patients with unilateral therapy made 721 visits: 280 visits (38.8%) were group A; 164 visits (22.8%) were group B and 277 visits (38.4%) were group C. Average interval in Group C was 8.9 weeks (range 5-15). The success rate of extension was 95.31% (264/277 visits). Conclusion These metrics for evaluating the decision making aspect of disease activity monitoring may be useful for monitoring performance and have given us a more realistic view and expectations of what can be achieved using this regime to optimise the timing of injections.

PURPOSE To find out clinical characteristics, therapeutic options, and visual outcome in symptomatic retinal artery macroaneurysm (RAMA) patients. METHOD Newly diagnosed cases of symptomatic RAMA from January 2015 to December 2019 were included. Fifteen eyes of 15 patients with mean age 62.46 years ± 14.89 (SD) fulfilled the inclusion criteria. RESULT Hypertension was present in 66.6% of the patients, and the commonest site was superotemporal (12 eyes, 80%). The most commonly employed treatment was Nd: Yag laser hyaloidotomy in 4 eyes (26.6%). Other treatments were intravitreal bevacizumab in 3 eyes (20%), focal laser with intravitreal bevacizumab in 3 eyes (20%), PPV with focal laser (13.3%) in 2, focal laser only in one (6.6%), PPV with focal and intravitreal bevacizumab in one (6.6%). The mean best-corrected visual acuity (BCVA) at baseline was 1.35 ± 0.84 LogMAR, which improved to 0.39 ± 0.53 LogMAR at the last follow-up. Presenting VA 0.77 (±0.40) improved to 0.20 (±0.17) p value (0.180) in intravitreal bevacizumab only group, 1.29 (±0.35) to 0.75 (±0.15) p value 0.66 in Nd: Yag laser group, 2.67 (±0.58) to 0.46 (±0.28) p value 0.019 in PPV group and did not improve in combined anti-VEGF and focal laser group due to dense hard exudates at the fovea in one and persistent cystoid macular edema in another case. CONCLUSION With regard to its presentation, which can vary tremendously, there are no approved guidelines for its treatment. The present study reinforces the need for a treatment guideline development. Customization of treatment should be considered depending on the clinical presentation of each case.

Purpose To identify anatomic endpoints altered by intravitreal ranibizumab in central retinal vein occlusion (CRVO) to determine any potential underlying disease modification that occurs with anti-vascular endothelial growth factor (anti-VEGF) therapy beyond best-corrected visual acuity and central optical coherence tomography outcomes. Methods A post hoc analysis of a double-masked, multicenter, randomized clinical trial was performed. A total of 392 patients with macular edema after CRVO were randomized 1:1:1 to receive monthly intraocular injections of 0.3 or 0.5 mg of ranibizumab or sham injections. Central reading center-read data were reviewed to explore potential anatomic endpoints altered by therapy. Results At 6 months, there was a reduction in the ranibizumab groups compared with sham groups with respect to total area of retinal hemorrhage (median change from baseline in disc areas: − 1.17 [sham], − 2.37 [ranibizumab 0.3 mg], − 1.64 [ranibizumab 0.5 mg]), development of disc neovascularization (prevalence: 3% [sham], 0% [ranibizumab 0.3 mg], 0% [ranibizumab 0.5 mg]), and presence of papillary swelling (prevalence: 22.9% [sham], 8.0% [ranibizumab 0.3 mg], 8.3% [ranibizumab 0.5 mg], p Conclusions Ranibizumab for CRVO resulted in beneficial disease-modifying effects through a reduction in retinal hemorrhage, neovascularization, and papillary swelling. These findings may form the basis for future work in the development of a treatment response or severity scale for eyes with CRVO.

This meta-analysis was conducted to evaluate the efficacy and safety of single-dose dexamethasone implantation for treating persistent DME (diabetic macular edema) refractory to anti-VEGF (anti-vascular endothelial growth factor) drugs over a period of 6 months. All related clinical trials were reviewed by searching electronic databases of PubMed, Medline, Web of Science, Cochrane Library, and EMBASE. The primary outcome parameters were best-corrected visual acuity (BCVA) and central macular thickness (CMT). We performed this meta-analysis by using Stata15.0. Ten clinical trials involving 362 eyes from 328 patients were eligible in the final analysis. After single-dose dexamethasone implantation, there was a significant improvement in BCVA from baseline to 1, 3, and 6 months with an average increase of − 0.15 logMAR (p

Anti-VEGF treatment for neovascular age-related macular degeneration (nAMD) has been evaluated in clinical trials. To select the best anti-VEGF drug and the best treatment regimen for nAMD, a thorough understanding of the characteristics of each anti-VEGF drug and treatment regimen is essential. In this review, we summarized visual acuity (VA) changes in 30 previous clinical trials of anti-VEGF treatment for nAMD. In most studies, ranibizumab, aflibercept, and brolucizumab improved the VA by 6 to 12 letters from the baseline VA of 50-65 letters and maintained the VA improvement regardless of the treatment regimen; the VA improved from 0.2-0.4 to 0.3-0.7 in Snellen equivalents. The improvement was rapid during the first month and became slower after the second injection, and 60% to 90% of the VA improvement was attained within the first 3 months. The upper limit of the VA improvement should be determined according to eyes with nAMD themselves, not according to anti-VEGF drugs or treatment regimens. Since a fixed regimen can result in overtreatment, whilst a pro re nata regimen can result in insufficient treatment, a treat-and-extend regimen would be optimal to treat nAMD. Insufficient treatment fails to improve VA to the upper limit and/or to maintain the improved VA, whereas overtreatment can cause macular atrophy. One study reported no difference in the risk of macular atrophy between ranibizumab and aflibercept, whilst many studies have suggested that aflibercept causes more choroidal thinning, one of the risk factors for macular atrophy, than does ranibizumab. Further evaluation of drugs and regimens should be performed from the viewpoint of complications and minimum number of injections required to improve and maintain VA.

Purpose The MERCURY study aimed to evaluate the effects on visual acuity and psychological symptoms, and safety, of ranibizumab and subsequent treatment in patients with diabetic macular oedema (DME) and impaired visual acuity (VA). We report data from the prespecified 12-month interim analysis. Methods This was a 24-month, phase 4, open-label, single-arm, prospective, observational study conducted at 20 specialised retinal centres in Japan. Participants were 209 patients with DME and impaired VA, not previously treated with either intravitreal or systemic anti-vascular endothelial growth factor (anti-VEGF) agents, who initiated ranibizumab 0.5 mg per investigator discretion. Following ranibizumab administration, patients were treated per routine clinical practice. Other treatments were allowed. The main outcome measure was the mean change in best-corrected VA (BCVA) in logarithmic minimum angle of resolution (logMAR) from baseline to month 12. An exploratory objective was to assess patients’ psychological status using the Hospital Anxiety and Depression Scale (HADS). Results The mean ± standard deviation BCVA at baseline was 0.43 ± 0.39 logMAR. The mean number of injections of ranibizumab and anti-VEGF agents from baseline to month 11 was 3.2 ± 2.0 and 3.6 ± 2.4, respectively. The BCVA change from baseline to 12 months was − 0.08 ± 0.34 logMAR (p = 0.011), showing a significant improvement; the HADS-anxiety score also decreased significantly (p = 0.001) and the depression score decreased numerically (p = 0.080). Conclusion MERCURY study data confirm the effectiveness of real-world treatment initiated with ranibizumab in Japanese patients with DME. In addition, treatment was able to positively influence anxiety via VA improvement.

Purpose To study the effect of anti-VEGF therapy for diabetic macular edema (DME) on retinal oxygen saturation (O2S) and its correlation with functional and anatomical changes of retinal tissue. Methods An interventional prospective single group study. Included were 10 eyes of 10 patients with visually significant DME which received a fixed regimen of intravitreal aflibercept every 4 weeks for 5 months, followed by 3 injections every 8 weeks, and were controlled monthly. Visual acuity (VA), central retinal thickness (CRT), arterial (aO2S), venous (vO2S) and arterio-venous difference (AVdO2S) retinal oxygen saturation were noted monthly. Changes after 5th (V6) injection and on last follow-up (V12) were studied. Correlations of different parameters were analyzed. Results The aO2S did not change whereas vO2S decreased (62.2 ± 9.4 pre-op to 57.2 ± 10.5 on V6, p = 0.03). This remained unchanged at 59.4 ± 13.2 on V12 (p = 0.2) and was accompanied by an increase of AVdO2S (40.8 ± 8.3 pre-op to 44.8 ± 10.6, p = 0.03 on V6) which was followed by a non-significant decrease to 41.8 ± 11.3 on V12 (p = 0.06). We found no correlation between BCVA and aO2S. However, mild correlation between BCVA and both vO2S and AVdO2S (r = −0.2 p = 0.035 and r = 0.185 p = 0.05 respectively) was found. No correlation was found between CRT and aO2S, vO2S, or AVdO2S. Conclusions During DME treatment with fixed regimen of intravitreal aflibercept over 11 months, we observed a reduction of vO2S and increase of AVdO2S which correlated with BCVA but not CRT. This could be explained by increasing consumption of O2S in the central retina and, possibly, by re-perfusion process.

Background Vascular endothelial growth factor inhibitors (VEGFIs) are used to treat malignant neoplasms and ocular diseases by inhibiting angiogenesis. Systemic use of VEGFIs has various side effects, including hypertension, proteinuria, and thrombotic microangiopathy, but adverse events due to intravitreal injection of VEGFIs have not been fully clarified. Although age-related macular degeneration was initially the most common target of intravitreal injection of VEGFIs, it has also been applied sporadically for diabetic macular edema in recent years. Proteinuria following intravitreal injection of VEGFIs would be reversible. In patients with diabetes mellitus (DM), however, it would be difficult to determine whether kidney damage arises from the clinical course of DM or from intravitreal injection of VEGFIs for diabetic macular edema. Case presentation A 55-year-old woman with a 20-year history of type 2 DM began intravitreal injection of VEGFI (aflibercept, 2 mg every 4 weeks) for treatment of diabetic macular edema 2 years previously. She presented with leg edema, hypertension, and nephrotic-range proteinuria 14 months after the first injection. Histological examination of renal biopsy specimens revealed diabetic nephropathy with renal thrombotic microangiopathy probably associated with intravitreal injection of VEGFI. The patient’s nephrotic syndrome completely improved at 6 months after simply discontinuing aflibercept. Conclusions This is a precious report of pathologically investigated renal thrombotic microangiopathy leading to nephrotic syndrome due to intravitreal injection of aflibercept for diabetic macular edema in a patient with type 2 DM. Renal function and proteinuria should be monitored in diabetic patients who receive intravitreal injection of a VEGFI. If kidney damage develops independent of the clinical course of DM during intravitreal injection of a VEGFI, renal biopsy should be performed and intravitreal VEGFI injection discontinued.

The optimal treatment of submacular hemorrhage (SMH) following neovascular age-related macular degeneration (nAMD) is controversial. This study aimed to compare visual outcomes of conservative versus active surgical treatment. Two hundred thirty-six eyes of 236 patients with SMH (≥ 1 disc diameter) were stratified into four groups: observation (n = 21); anti-vascular endothelial growth factor (VEGF) monotherapy (n = 161); non-surgical gas tamponade (n = 31); and subretinal surgery (n = 23). The primary outcome was best-corrected visual acuity (BCVA) at 12 months. The baseline BCVAs of the observation, anti-VEGF monotherapy, non-surgical gas tamponade, and subretinal surgery groups were 1.50 ± 0.70, 1.09 ± 0.70, 1.31 ± 0.83, and 1.62 ± 0.77 logarithm of minimal angle resolution (LogMAR), respectively. The mean BCVAs at 12 months were 1.39 ± 0.84, 0.90 ± 0.83, 1.35 ± 0.88, and 1.44 ± 0.91 LogMAR, respectively. After adjusting for age, baseline BCVA, SMH size, and the number of intravitreal anti-VEGF injections before SMH, the mean BCVA showed no significant difference among treatments at 12 months (P = 0.204). The anti-VEGF monotherapy group showed better mean BCVA significantly at 3 months (P P

To study treatment outcomes of combination treatment of intravitreal anti-vascular endothelial growth factor (VEGF) injection and laser photocoagulation in Type 1 Retinopathy of Prematurity (ROP) and Aggressive Posterior ROP (APROP). This is a retrospective observational study of 87 eyes of 48 premature babies who presented with Type I ROP or APROP and were treated with combination of laser and anti-VEGF therapy. Retrospective evaluation of case records was done to collect data on gestational age, birth weight, age at intervention, anterior segment and fundus findings, intervention with laser and anti-VEGF and response to treatment. Outcome measure was defined as attached retina at posterior pole at last follow-up. Mean gestational age was 29.1 weeks, and mean birth weight was 1226.9 gms. Sixty-six (75.8%) eyes had Type I ROP and 21 (24.1%) eyes had APROP at presentation. Five eyes (3 patients) were lost to follow-up after treatment. Of 82 eyes, 80.5% (66 eyes) showed regression of ROP following combination treatment and 19.5% (16 eyes) needed surgery. Of these, 15 underwent surgery and 12 had successful outcome. Mean follow-up duration of patients was 52 weeks. Finally, 95.1% (78 eyes) had attached retina at posterior pole and 4.9% (4 eyes) had detached retina. We conclude that combination therapy is an effective and safe treatment strategy for Type I ROP and APROP.

OBJECTIVE To understand intraocular pressure (IOP) response after switching from intravitreal bevacizumab (IVB) and/or ranibizumab (IVR) to intravitreal aflibercept (IVA) for treatment-resistant neovascular age-related macular degeneration (nAMD) in patients with and without coexisting glaucoma-related diagnoses. METHODS Retrospective, cross-sectional comparative case series of 62 eyes of 58 patients treated with intravitreal injection for nAMD from March 2010 to April 2018. Patients with glaucoma-related diagnoses, defined here as open-angle glaucoma or suspicion of open-angle glaucoma, ocular hypertension, and/or narrow-angle glaucoma, were compared to those without glaucoma. IOP data were collected at baseline, at the three visits where patients received loading doses of IVB/IVR, and at all of the visits following the switch to IVA through the end of follow-up. RESULTS 19 eyes with pre-existing glaucoma-related diagnoses were compared to 43 eyes without such diagnoses. Baseline IOP was similar for glaucoma and non-glaucoma patients. The loading doses of IVB/IVR did not impact IOP; however, a small, sustained rise in IOP was noted among patients with glaucoma-related diagnoses by the final IVB/IVR injections before the switch to IVA (∆IOP 1.61 ± 0.52 mmHg, P

The delivery of drugs to the posterior segment of the eye remains a tremendously difficult task. Prolonged treatment in conventional intravitreal therapy requires injections that are administered frequently due to the rapid clearance of the drug molecules. As an alternative, intraocular implants can offer drug release for long-term therapy. However, one of the several challenges in developing intraocular implants is selecting an appropriate in vitro dissolution testing model. In order to determine the efficacy of ocular implants in drug release, multiple in vitro test models were emerging. While these in vitro models may be used to analyse drug release profiles, the findings may not predict in vivo retinal drug exposure as this is influenced by metabolic and physiological factors. This review considers various types of in vitro test methods used to test drug release of ocular implants. Importantly, it discusses the challenges and factors that must be considered in the development and testing of the implants in an in vitro setup. Graphical abstract