Switching to the aflibercept (3 mg) therapy for treatment-resistant wet age-related macular degeneration: 1-year outcomes.

This study aimed to elucidate 1-year outcomes following switching to the aflibercept (3 mg) therapy for treatment-resistant wet age-related macular degeneration (wAMD). In this prospective, open-label, non-controlled clinical trial, 18 patients with wAMD who had multiple recurrences or persistent exudation despite intravitreal injections of anti-vascular endothelial growth factor agents (except aflibercept) received a 3-mg intravitreal aflibercept injection every 4 weeks. Each patient received 3 to 8 injections. The central retinal thickness and fibrovascular pigment epithelial detachment height decreased significantly at 1 month after initiation of the aflibercept injection, and the values were 146 and 163.2 µm, respectively, at the final visit. The morphological improvement was sustained. The intraretinal and subretinal fluid was completely absorbed at the end of the follow-up. The logMAR vision increased from baseline 0.68 to 0.59 (P < .05). No ocular or systemic adverse events occurred. The intravitreal injection of 3-mg aflibercept seems to be feasible in the treatment of wAMD unresponsive to other anti-vascular endothelial growth factor agents.

Long-term outcomes of anti-vascular endothelial growth factor therapy with and without posterior scleral reinforcement on myopic maculopathy in myopic choroidal neovascularization eyes.

BACKGROUND: Anti-vascular endothelial growth factor (anti-VEGF) therapy is used for myopic choroidal neovascularization (mCNV). Patchy chorioretinal atrophy (pCRA) enlargement has been reported in mCNV cases associated with vision loss. Our aim was to compare the long-term effectiveness of anti-VEGF therapy alone versus anti-VEGF followed by posterior scleral reinforcement (PSR) in controlling myopic maculopathy in mCNV eyes. METHODS: We performed a retrospective review of the medical records of 95 high myopia patients (refractive error ≥ 6.00 diopters, axial length ≥ 26.0 mm) with mCNV. Patients were treated with anti-VEGF alone (group A) or anti-VEGF followed by PSR (group B). The following data were collected: refractive error, best corrected visual acuity (BCVA), ophthalmic fundus examination, ocular coherence tomography and ocular biometry at 12 and 24 months pre- and postoperatively. The primary outcomes were changes in pCRA and BCVA. RESULTS: In 26 eyes of 24 patients, the mean pCRA size significantly increased from baseline (0.88 ± 1.69 mm2) to 12 months (1.57 ± 2.32 mm2, t = 3.249, P = 0.003) and 24 months (2.17 ± 2.79 mm2, t = 3.965, P = 0.001) postoperatively. The increase in perilesional pCRA in group B (n = 12) was 98.2% and 94.2% smaller than that in group A (n = 14) at 12 and 24 months (Beta 0.57 [95% CI 0.01, 191 1.13], P = 0.048). In group B, 7 eyes (58.3%) gained more than 2 lines of BCVA compared with only 4 eyes (28.6%) in group A at 24 months. CONCLUSION: Anti-VEGF therapy followed by PSR achieved better outcomes than anti-VEGF therapy alone in controlling the development of myopic maculopathy in mCNV and may constitute a better treatment option by securing a better long-term VA outcome.

Enhanced durability and evolution of retreatment criteria of intravitreal antivascular endothelial growth factor agents for diabetic macular edema.

PURPOSE OF REVIEW: The increasing prevalence of diabetic macular edema (DME) necessitates an updated review of treatment modalities. While the shift from laser to anti-vascular endothelial growth factor (anti-VEGF) therapy has transformed patient outcomes, benefits of these agents are not fully realized in real-world implementation relative to the setting of controlled clinical trials. This review outlines the evolution of intravitreal anti-VEGF treatment extension protocols for DME that reflect efforts to address treatment adherence challenges while optimizing visual outcomes. RECENT FINDINGS: Recent studies highlight the efficacy of extended-interval dosing with anti-VEGF agents in managing DME. Trials such as RISE/RIDE, VISTA/VIVID, and LUCIDATE have established the foundation of these regimens by demonstrating sustained visual gains with continuous treatment. However, newer trials including PROTOCOL T, KESTREL/KITE, YOSEMITE/RHINE, and PHOTON have furthered this concept, revealing that less frequent dosing of various anti-VEGF agents can maintain similar visual acuity and anatomical outcomes to traditional monthly injections. SUMMARY: The reviewed findings suggest a paradigm shift in DME treatment toward less frequent anti-VEGF injections. This has significant implications for clinical practice, potentially leading to greater adherence to treatment regimens and sustained visual function in patients, while minimizing treatment burden and healthcare costs. Further investigation into the long-term effects of extended dosing intervals is required.

Sodium-glucose co-transporter 2 inhibitor therapy reduces the administration frequency of anti-vascular endothelial growth factor agents in patients with diabetic macular oedema with a history of anti-vascular endothelial growth factor agent use: A cohort study using the Japanese health insurance claims database.

AIM: We assessed the effectiveness of sodium-glucose co-transporter 2 inhibitors (SGLT2is) in reducing the administration frequency of anti-vascular endothelial growth factor (VEGF) agents in patients with diabetic macular oedema (DMO) using a health insurance claims database. MATERIALS AND METHODS: This retrospective cohort study analysed health insurance claims data covering 11 million Japanese patients between 2005 and 2019. We analysed the frequency and duration of intravitreal injection of anti-VEGF agents after initiating SGLT2is or other antidiabetic drugs. RESULTS: Among 2412 matched patients with DMO, the incidence rates of anti-VEGF agent injections were 230.1 per 1000 person-year in SGLT2i users and 228.4 times per 1000 person-year in non-users, respectively, and the risk ratio for events was unchanged in both groups. Sub-analysis of each baseline characteristic of the patients showed that SGLT2is were particularly effective in patients with a history of anti-VEGF agent use [p = .027, hazard ratio (HR): 0.44, 95% confidence interval (CI): 0.22-0.91]. SGLT2is reduced the risk for the first (p = .023, HR: 0.45, 95% CI: 0.22-0.91) and second (p = .021, HR: 0.39, 95% CI: 0.17-0.89) anti-VEGF agent injections. CONCLUSIONS: There was no difference in the risk ratio for the addition of anti-VEGF therapy between the two treatment groups. However, the use of SGLT2is reduced the frequency of anti-VEGF agent administration in patients with DMO requiring anti-VEGF therapy. Therefore, SGLT2i therapy may be a novel, non-invasive, low-cost adjunctive therapy for DMO requiring anti-VEGF therapy.

Patterns of anti-vascular endothelial growth factor discontinuation in neovascular age-related macular degeneration.

OBJECTIVE: To report on anti-vascular endothelial growth factor (anti-VEGF) discontinuation in neovascular age-related macular degeneration (nAMD). DESIGN: Retrospective cohort study. PARTICIPANTS: Treatment-naive nAMD patients initiating anti-VEGF injections between 2015 and 2021. METHODS: Demographics, treatment start and end dates, number of injections, treatment length, reason for discontinuation, and baseline and final data (i.e., age, best-corrected visual acuity, and central subfield thickness) were recorded. Statistical analyses using STATA 17.0 assessed differences between baseline and final values and between treatment-discontinuation subgroups. RESULTS: A total of 619 eyes of 502 treatment-naive patients (9015 injections) were included (age, 81.6 ± 8.4 years; 64.0% female). Discontinuation rate was 58.3% (361 of 619), with 310 patients discontinuing because of the lack of visual benefit (n = 152), severe comorbidity or death (n = 82), transferred (n = 33), stable off active treatment (n = 19), lack of benefit plus stable off treatment (n = 14), patient decision (n = 6), and ocular comorbidity (n = 4). Among the 309 remaining patients, 51 (16.5%) were lost to follow-up. Discontinuation occurred within the first year in 49.3% (n = 178). Visual acuity was at least maintained in all groups and improved in the following groups: severe comorbidity or death (p < 0.0001), lost to follow-up (p = 0.0003), transferred (p = 0.0004), and stable off treatment (p = 0.0053). The lack of visual benefit group had no improvement in vision regardless of treatment length. Compared with other subgroups, those stable off treatment group was younger (p = 0.0055), had better baseline vision (p = 0.0018), received more injections (p = 0.0437) over a longer time (p = 0.0034), and achieved better final vision (p < 0.0001). CONCLUSION: While there was a high discontinuation rate over 7.5 years, most were attributable to disease or treatment factors and nonmodifiable patient factors. Discontinuation frequently occurred within the first year.

The efficacy of different anti-vascular endothelial growth factor agents, and dexamethasone implant therapy in patients with serous retinal detachment caused by Irvine-Gass syndrome.

PURPOSE: The aim of this study is to compare the efficacy of intravitreal aflibercept (IVA), bevacizumab (IVB), ranibizumab (IVR), and dexamethasone implant (IVDI) in the treatment of serous retinal detachment (SRD) caused by Irvine-Gass syndrome (IGS). DESIGN: Retrospective cohort, comparative study. METHODS AND MATERIALS: The medical records of 128 eyes with no previous history of intravitreal agents in 128 IGS patients with SRD that received IVA, IVB, IVR, and IVDI monotherapy were retrospectively reviewed. The patients were divided into 4 groups, according to treatment. Patients with recurrence and/or were unresponsive following a course of topical steroids and non-steroidal anti-inflammatory drugs (NSAIDs) were included in the study. Best corrected visual acuity (BCVA), central macular thickness (CMT), subfoveal choroidal thickness (SFCT), and SRD were compared between the 4 treatment groups at baseline, at follow-up months 1, 3, 6, and 12, and at the final follow-up visit. RESULTS: Serous retinal detachment completely resolved in 74%, 45.7%, 66.4%, and 40.8% of the eyes at month 1 (P = 0.042), 87%, 50.9%, 75.8%, and 80.9% at month 3 (p = 0.031), 88.9%, 50.4%, 75.7%, 80.2% at month 6 (p = 0.028), 81.7%, 72.8%, 68.7%, 80.1% at month 12 (p = 0.580), and 100%, 66.4%, 87.9%, 93.2% (p = 0.478) at final follow-up visit in the IVA, IVB, IVR, and IVDI groups, respectively. BCVA was significantly better in the IVA group at all follow-up time points (month 1: p < 0.001; month 3: p < 0.001; month 6: p = 0.002; month 12: p = 0.009, final follow-up visit: p < 0.001). CMT was significantly lower in the IVA group at months 3 (p = 0.008), 6 (p = 0.011), and 12 (p = 0.010), and at the final follow-up visit (p < 0.001). Recurrence was observed after a longer period of time and fewer injections were needed in the IVDI and IVA groups (p < 0.05). Resolution of CME was most rapid in the IVA group (p = 0.032). CONCLUSION: All intravitreal agents were effective in terms of visual results in the SRD patients; however, eyes treated with IVA and IVDI required fewer injections, as compared to the eyes treated with IVB and IVR. Furthermore, SRD entirely resolved in all eyes in the IVA group at the final follow-up visit.

Intravitreal Injection of Anti-Vascular Endothelial Growth Factors Combined with Corticosteroids for the Treatment of Macular Edema Secondary to Retinal Vein Occlusion: A Systematic Review and Meta-Analysis.

PURPOSE: To evaluate the efficacy and safety of intravitreal anti-vascular endothelial growth factor (anti-VEGF) and corticosteroid combination therapy for the management of treatment-naïve or recurrent/refractory macular edema caused by retinal vein occlusion (RVO) in comparison with anti-VEGF monotherapy. METHODS: In this systematic review and meta-analysis study, the data from publications in the electronic databases including PubMed, Embase, Cochrane Library Central Register of Controlled Trials, ISI and Scopus from January 1, 2007, through November 20, 2020, were compiled. Heterogeneity was statistically quantified by the I2 statistic, and meta-analysis was performed using a random-effects model. RESULTS: Twenty-four related studies were identified, including a total of 1280 eyes, which consisted of 685 and 507 patients with central retinal vein occlusion (CRVO) and branch retinal vein occlusion (BRVO), respectively. This study demonstrated a greater improvement in best-corrected visual acuity (BCVA) in the combination group compared to anti-VEGF monotherapy for both CRVO and BRVO cases at 6 months after initiating therapy. The improvement in vision was more notable in BRVO cases than in CRVO cases. However, the changes in central macular thickness (CMT) did not differ significantly between the different treatment approaches, and the results were inconclusive. Including all cases with RVO, there was no inferiority in terms of BCVA improvement and CMT reduction in the triamcinolone subgroup compared with the slow-release dexamethasone implant subgroup. A greater improvement was noticed in terms of BCVA in the sequentially treated subgroup compared to the simultaneous treatment subgroup, while there was a greater reduction in CMT in the simultaneous subgroup with the highest reduction recorded at 1 month after treatment. CONCLUSIONS: This study suggests that combination therapy with intravitreal anti-VEGF and corticosteroid (such as intravitreal or subtenon triamcinolone or dexamethasone implant) has a slightly better effect on improving BCVA in cases with BRVO or CRVO at 6 months compared to monotherapy.

Suboptimal outcomes and treatment burden of anti-vascular endothelial growth factor treatment for diabetic macular oedema in phakic patients.

OBJECTIVES: In England and Wales, treatment options were limited for patients with diabetic macular oedema (DMO) with phakic eyes that failed anti-vascular endothelial growth factor (anti-VEGF) treatment pre-2022. This study aimed to quantify the response to, and treatment burden of, anti-VEGF treatment in phakic eyes. METHODS: Retrospective, cohort study using electronic patient record data from two UK centres between 2015 and 2020. Primary objective was proportion of phakic eyes with a suboptimal response after initial 6 months of anti-VEGF treatment. Data were available for 500 eyes from 399 patients. RESULTS: At 6 months significantly more eyes had a suboptimal response to anti-VEGF treatment: 65.8% (95% CI 61.5-70.0%) vs 34.2% (95% CI 30.0-38.5%), p < 0.0001. Baseline visual acuity (VA) predicted VA outcome, however, despite greater gains in eyes with poorer VA, such eyes did not achieve the same VA levels as those who started treatment with better VA. Only 53.6% of eyes had more than three injections in the first 6 months indicating difficulties in delivering high volume/high frequency treatment. Treatment and review burden were similar over the following years regardless of response to anti-VEGF treatment. CONCLUSIONS: Data confirm previous real world evidence around response to anti-VEGF treatment, importance of baseline VA and frequency of injections in predicting outcomes in a UK setting. Continuing treatment beyond 6 months in suboptimal responders imposes unnecessary treatment burden without significant change in VA. In suboptimal responders, consideration of early switch to longer acting steroid treatments may help to reduce treatment burden, whilst maintaining or improving vision.

Evaluation of optical coherence tomography biomarkers to differentiate favourable and unfavourable responders to intravitreal anti-vascular endothelial growth factor treatment in retinopathy of prematurity.

OBJECTIVE: Evaluation of optical coherence tomography biomarkers in predicting treatment response to intravitreal injection of anti-vascular endothelial growth factor (anti-VEGF) Bevacizumab, in aggressive retinopathy of prematurity (A-ROP). METHODS: Non-contact ultra-widefield (NC-UWF) fundus imaging with integrated UWF guided swept source Optical coherence tomography (SS-OCT) was performed prospectively in preterm babies before and after intravitreal anti-VEGF (Bevacizumab) monotherapy. OCT biomarkers were analysed in eyes that reached complete vascularization versus others. RESULTS: Eyes with retinal vessels reaching near ora serrata were labelled as regressed ROP and vascularised retina (Group1). Eyes with reactivation of ROP needing laser or vitreoretinal surgery or eyes with peripheral avascular retina (PAR) at 16th week post-injection were considered as Group 2. Pre-injection baseline OCT showed a hyperreflectivity of inner retinal layers in 12 out of 46 eyes in Group 1 versus 30 out of 34 eyes in Group 2 (p value 0.002). None of the eyes in Group 1 showed choroidal thinning at posterior pole as compared to 14 out of 34 eyes in Group 2 (p value 0.001). Intraretinal hypo reflective Cystic changes at fovea were seen in 16 out of 46 eyes in Group 1 and 2 out of 34 eyes in Group 2 (p value 0.012). CONCLUSION: Pre-injection swept source OCT biomarkers could predict the treatment outcomes of anti-VEGF (Bevacizumab) monotherapy in A-ROP eyes. Hyperreflectivity of inner retinal layers and choroidal thinning had poorer and unpredictable response to anti-VEGF injection whereas, cystic changes at fovea predicted favourable response.

Intravitreal anti-vascular endothelial growth factor injections in pregnancy and breastfeeding: a case series and systematic review of the literature.

INTRODUCTION: Anti-vascular endothelial growth factor (anti-VEGF) agents may occasionally need to be considered for sight-threatening macular pathology in pregnant and breastfeeding women. This is controversial due to the dearth of data on systemic side effects for mother and child. We aimed to expand the evidence base to inform management. METHODS: Retrospective case series of pregnant and breastfeeding women treated with intravitreal anti-VEGF injections at Oxford Eye Hospital between January 2015 and December 2022. In addition, we conducted a systematic review and combined eligible cases in a narrative synthesis. RESULTS: We treated six pregnant women with anti-VEGF for diabetic macular oedema(DMO) (n = 5) or choroidal neovascularisation (CNV) (n = 1). Four received ranibizumab whilst two (not known to be pregnant) received aflibercept. Patients known to be pregnant underwent counselling by an obstetric physician. Five pregnancies resulted in live births. Combining our cases with those previously published, treatment of 41 pregnant women (42 pregnancies) are reported. Indications for treatment included CNV (n = 28/41,68%), DMO (n = 7/41,17%) and proliferative diabetic retinopathy (n = 6/41,15%). Bevacizumab (n = 22/41,54%) and ranibizumab (n = 17/41,41%) were given more frequently than aflibercept (n = 2/41,5%). Many (n = 16/41,40%) were unaware of their pregnancy when treated. Most pregnancies resulted in live births (n = 34/42,81%). First trimester miscarriages (n = 5/42,12%) and stillbirths (n = 3/42,7%) mostly occurred in women with significant risk factors. CONCLUSION: Intravitreal anti-VEGF injections may not necessarily compromise obstetric outcomes, although clear associations cannot be drawn due to small numbers and confounders from high rates of first trimester miscarriages in general and inherently high-risk pregnancies. It may be worth considering routinely investigating pregnancy and breastfeeding status in women of childbearing age prior to each injection, as part of anti-VEGF treatment protocols.

Cost-effectiveness of the anti-vascular endothelial growth factor intravitreal injection and panretinal photocoagulation for patients with proliferative diabetic retinopathy in South Korea.

BACKGROUND: We determined the cost-effectiveness of the anti-vascular endothelial growth factor (VEGF) intravitreal injection versus panretinal photocoagulation (PRP) for patients with proliferative diabetic retinopathy (PDR) in South Korea. METHODS: We simulated four treatment strategies using PRP and the anti-VEGF injection by constructing a Markov model for a hypothetical cohort of 50-year-old PDR patients: (1) PRP only; (2) anti-VEGF injection only; (3) PRP first; and (4) anti-VEGF injection first. RESULTS: In this cost-effectiveness analysis, compared with only-PRP, the incremental cost-effectiveness ratio was $95,456 per quality-adjusted life-year (QALY) for PRP first, $34,375 per QALY for anti-VEGF injection first, and $33,405 per QALY for anti-VEGF injection only from a healthcare perspective. From the societal and payer perspective, strategy (2) was more cost-saving and effective than (1). In the probabilistic sensitivity analysis, only-PRP was cost-effective up to the willingness-to-pay (WTP) of about $42,000, while anti-VEGF injection only was cost-effective from a healthcare perspective. From the societal and payer perspectives, regardless of the value of WTP, anti-VEGF injection only was the most cost-effective strategy. CONCLUSION: In our study, the anti-VEGF injection for PDR was cost-effective from the payer and societal perspectives.

Real-World Outcomes of Intravitreal Anti-Vascular Endothelial Growth Factor Treatment for Diabetic Macular Edema in Türkiye: MARMASIA Study Group Report No. 1.

Objectives: This study aimed to report the demographic and clinical characteristics of diabetic macular edema (DME) patients treated with intravitreal injection (IVI) of anti-vascular endothelial growth factors (anti-VEGF) and provide an overview of outcomes during routine clinical practice in Türkiye. Materials and Methods: This retrospective, real-world study included 1,372 eyes (854 patients) treated with a pro re nata protocol by 21 ophthalmologists from 8 tertiary clinics on the Asian side of the Marmara region of Türkiye (MARMASIA Study Group). Five cohort groups were established by collecting the patients' baseline and 3, 6, 12, 24, and 36-month follow-up data, where each subsequent cohort may include the previous. Changes in best-corrected visual acuity (BCVA, approximate ETDRS letters) and central macular thickness (CMT, µm), number of visits and IVI, and rates of anti-VEGF switch and intravitreal dexamethasone implant (IDI) combination were evaluated. Results: The 3, 6, 12, 24, and 36-month cohorts included 1372 (854), 1352 (838), 1185 (722), 972 (581), and 623 (361) eyes (patients), respectively. The mean baseline BCVA and CMT were 51.4±21.4 letters and 482.6±180.3 µm. The mean changes from baseline in BCVA were +7.6, +9.1, +8.0, +8.6, and +8.4 letters, and in CMT were -115.4, -140.0, -147.9, -167.3, and -215.4 µm at the 3, 6, 12, 24, and 36-month visits (p<0.001 for all). The median cumulative number of anti-VEGF IVI was 3.0, 3.0, 5.0, 7.0, and 9.0, respectively. The overall anti-VEGF switch and IDI combination rates were 18.5% (253/1372 eyes) and 35.0% (480/1372 eyes), respectively. Conclusion: This largest real-life study of DME from Türkiye demonstrated BCVA gains inferior to randomized controlled trials, mainly due to the lower number of IVI. However, with the lower baseline BCVA and higher IDI combination rates in our cohorts, these gains were relatively superior to other real-life study counterparts.

Seven-year outcomes of combined treatment of anti-vascular endothelial growth factor with photodynamic therapy for polypoidal choroidal vasculopathy; according to polypoidal lesion regression.

PURPOSE: To evaluate the long-term prognosis of polypoidal choroidal vasculopathy (PCV) treated with anti-vascular endothelial growth factor (anti-VEGF) combined with verteporfin photodynamic therapy (PDT), according to polypoidal lesion regression. METHODS: This study retrospectively reviewed the data of 33 naïve eyes with PCV treated with anti-VEGF combined with verteporfin PDT and followed-up for at least 7 years. The collected data included demographic profile, best-corrected visual acuity (BCVA), central foveal thickness (CFT), PED volume, and presence of submacular hemorrhage. Regression of polypoidal lesion was determined using indocyanine green angiography and optical coherence tomography. All eyes were divided into regression or persistent groups, based on the polypoidal lesion regression one year after the initial combined treatment. RESULTS: BCVA improvement was maintained for 3 years in the regression (p = 0.001) and 1 year in the persistent (p = 0.006) groups, respectively. The mean BCVA of the regression group was better than that of the persistent group over 7 years, but the difference was significant only at 1 year (p = 0.037). The number of eyes which maintained BCVA less than or equal to 0.3 logMAR at 7 years was 11 eyes (64.7%) in regression group and 4 eyes (25.0%) in persistent group (p = 0.022). CONCLUSIONS: Regression of the polypoidal lesion at 1 year after the initial combination treatment was associated with favorable long-term visual prognosis, particularly in terms of maintaining good visual acuity.

AREDS2 Supplementation in Patients with Wet Age-Related Macular Degeneration.

BACKGROUND: In recent years, major progress has been made in treating the wet form of age-related macular degeneration (AMD) with anti-vascular endothelial growth factors, which reportedly stabilize and improve vision. OBJECTIVES: To examine the effect of dietary supplementation, as recommended by the Age-Related Eye Disease Study 2 (AREDS2), on the number of anti-vascular endothelial growth factor injections administered to patients with wet AMD. METHODS: A retrospective study was conducted with 57 participants (27 participants in the study group and 30 in the control group) receiving injections of anti-vascular endothelial growth factors. The study group received dietary supplements for at least one year before the treatment was initiated, while the control group did not. Primary outcome was the number of injections a patient received over a 3-year period. Secondary outcomes were central macular thickness and visual acuity. RESULTS: The average number of injections per patient after 3 years was 21.89 ± 7.85 in the study group and 26.00 ± 5.62 in the control group (P = 0.083). Final visual acuities were 0.45 ± 0.45 and 0.8 ± 0.73 (P = 0.09), and final central macular thicknesses were 288.26 ± 55.38 and 313.12 ± 107.36 (P = 0.38) in the study and control groups, respectively. CONCLUSIONS: The average number of injections after 3 years was lower in the study group, but this difference did not reach statistical significance. No statistically significant difference was found in final visual acuity or central macular thickness between the groups.

Case Report: Branch Retinal Vein Occlusion Post-mRNA SARS-CoV-2 (COVID-19) Vaccination.

SIGNIFICANCE: Systemic thromboembolic complications are well documented to be associated with coronavirus disease 2019 (COVID-19); however, there have been a growing number of reports regarding ocular complications stemming from COVID-19 vaccinations. This case illustrates a clear temporal and possible causal relationship of COVID-19 vaccination with an ocular microvascular disorder, namely, retinal vein occlusion. PURPOSE: This study aimed to report a case of inferotemporal branch retinal vein occlusion after messenger RNA Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination. CASE REPORT: A middle-aged woman developed right eye central scotoma 2 days after COVID-19 vaccination. She had transient hypertension during the first 2 days post-vaccination. A decrease in visual acuity (6/18) was documented. Initial retinal findings included flame-shaped hemorrhages and cotton-wool spots along inferotemporal branch retinal vessels. Optical coherence tomography revealed right eye cystoid macular edema. Laboratory investigation revealed mildly raised erythrocyte sedimentation rate and C-reactive protein. Other systemic examinations were unremarkable. She was treated for right eye inferotemporal branch retinal vein occlusion with cystoid macular edema and was given intravitreal anti-vascular endothelial growth factor monthly in three doses. Her visual acuity improved to 6/6 with resolved cystoid macular edema. CONCLUSIONS: This case illustrates a clear temporal and possible causal relationship between COVID-19 vaccination and retinal vein occlusion. Post-vaccination transient hypertension or the immunological and inflammatory response to the vaccine may have contributed to the venous occlusive event in this case. Eye care providers should remain aware of this possibility. The effectiveness of intravitreal anti-vascular endothelial growth factor for the treatment of macular edema secondary to branch retinal vein occlusion was demonstrated in this patient.

Is there a relationship between the first-day results of anti-VEGF therapy for macular edema due to vascular diseases and longterm outcomes?

PURPOSE: To evaluate early changes after the first antivascular endothelial growth factor injection for macular edema secondary to diabetic retinopathy and retinal vein occlusion and the relationship between longterm outcomes. METHODS: The study enrolled patients who received anti-vascular endothelial growth factor injections for treatment-naive macular edema due to retinal vein occlusion and diabetic retinopathy. The central macular thickness was measured at baseline, post-injection day 1, week 2, and month 1, and at the last visit using spectral-domain optical coherence tomography. A good response was defined as a central macular thickness reduction of ≥10% on post-injection day 1. Patients were reassessed at the last visit with regard to treatment response on post-injection day 1 based on the favorable anatomic outcome defined as a central macular thickness <350 µm. RESULTS: In total, 26 (44.8%) patients had macular edema-retinal vein occlusion and 32 (55.2%) had macular edema-diabetic retinopathy. The mean follow-up time was 24.0 (SD 8.5) months. A statistically significant decrease in the central macular thickness was observed in both patients with macular edema-retinal vein occlusion and macular edema-diabetic retinopathy after antivascular endothelial growth factor injection therapy (p<0.001 for both). All patients with macular edema-retinal vein occlusion were good responders at post-injection day 1. All nongood responders at post-injection day 1 belong to the macular edema-diabetic retinopathy group (n=16.50%). The rate of hyperreflective spots was higher in nongood responders than in good responders of the macular edema-diabetic retinopathy group (p=0.03). Of 42 (2.4%) total good responders, one had a central macular thickness >350 µm, whereas 5 (31.2%) of 16 total nongood responders had a central macular thickness >350 µm at the last visit (p=0.003). CONCLUSION: The longterm anatomical outcomes of macular edema secondary to retinal vein occlusion and diabetic retinopathy may be predicted by treatment response 1 day after antivascular endothelial growth factor injection.

Acute Kidney Injury from Intravitreal Anti-vascular Endothelial Growth Factor Drugs: A Systematic Review and Meta-analysis of Randomized Controlled Trials.

BACKGROUND: Several observational studies have reported acute kidney injury from intravitreal anti-vascular endothelial growth factor (anti-VEGF) drugs for retinal diseases. However, systematic reviews and meta-analyses of randomized controlled trials on this critical topic are scant. OBJECTIVE: To evaluate acute kidney injury risk associated with intravitreal anti-VEGF drugs in patients with retinal diseases. METHODS: We searched PubMed, Embase, and the Cochrane Central Register of Controlled Trials on 12 July, 2023, and included randomized controlled trials reporting acute kidney injury between anti-VEGF drugs (e.g., aflibercept, bevacizumab, brolucizumab, and ranibizumab) and controls for retinal diseases (e.g., age-related macular degeneration, polypoidal choroidal vasculopathy, diabetic retinopathy/diabetic macular edema, retinal vein occlusion, and myopic choroidal neovascularization). Data were synthesized by a fixed-effects model for pooling odds ratios (ORs) using the Peto method. RESULTS: We included 13 randomized controlled trials (four and nine trials for aflibercept and ranibizumab, respectively) with a total of 4282 participants. The meta-analysis indicated intravitreal anti-VEGF drugs did not increase the acute kidney injury risk, compared with controls (odds ratio [OR]: 1.00, 95% confidence interval [CI] 0.49-2.04, I2: 0%), and no differences in the acute kidney injury risk were observed between different anti-VEGF drugs (OR: 1.10, 95% CI 0.27-4.43, I2: 0% for aflibercept; OR: 0.97, 95% CI 0.42-2.22, I2: 0% for ranibizumab) and between different retinal diseases (OR: 4.61, 95% CI 0.07-284.13, I2: not applicable for age-related macular degeneration; OR: 0.90, 95% CI 0.42-1.93, I2: 0% for diabetic retinopathy/diabetic macular edema; OR: 1.57, 95% CI 0.16-15.88, I2: 0% for retinal vein occlusion). CONCLUSIONS: Intravitreal anti-VEGF drugs were not associated with an acute kidney injury risk, regardless of which anti-VEGF drugs (aflibercept or ranibizumab) or retinal diseases (age-related macular degeneration, diabetic retinopathy/diabetic macular edema, or retinal vein occlusion) were involved. SYSTEMATIC REVIEW PROTOCOL REGISTRATION: PROSPERO CRD42021267854.

Distance and near vision changes after intravitreal anti-vascular endothelial growth factor injection in eyes with center-involving diabetic macular edema.

Purpose: To elucidate distance and near vision changes after intravitreal injections in center-involving diabetic macular edema (CIDME) in phakic and pseudophakic groups. Methods: A retrospective study was done on 148 eyes (72 phakic and 76 pseudophakic) with center-involving DME. All eyes were treated with intravitreal anti-vascular endothelial growth factor (VEGF) injection. All patients underwent distance best-corrected visual acuity (BCVA) testing, near BCVA testing, dilated fundus examination, and optical coherence tomography (OCT) at baseline and follow-up visits. Eyes that could not improve after the first injection were given 2nd, 3rd, and more injections in the subsequent visits. Results: On follow-up, post injections in the phakic group (n = 72), there were 65 eyes (90.3%) with stable/improved near vision and 59 eyes (81.9%) with stable/improved distance vision, whereas in the pseudophakic group (n = 76), 63 eyes (82.9%) and 60 eyes (78.9%), respectively. Both in phakic and pseudophakic eyes, 7.7%-13% of the cohort showed only near vision improvement. Conclusion: In DME, besides the changes in distance vision, there are also changes in near vision. These changes should be taken into account while determining the response to anti-VEGF in DME treatment.