Anti-vascular Endothelial Growth Factor Agents Research Articles

Retinal non-perfusion in diabetic retinopathy.

Diabetic retinopathy is a major cause of vision loss worldwide and areas of retinal non-perfusion (RNP) are a key pathologic feature of the vascular component of diabetic retinopathy. While there is a need for a more complete understanding of the natural history of RNP development and progression, overall, increasing RNP has been closely linked with worsening DR severity. Both traditional and novel approaches to quantitative image assessment are being explored to advance our understanding of the vascular, physiologic and functional changes associated with progressive RNP. Retinal ischemia secondary to RNP leads to tissue hypoxia and changes in the expression of a host of signalling molecules. Current anti-vascular endothelial growth factor and steroid pharmaceutical agents appear to be unable to reperuse areas of RNP, but may be able to slow the progressive longitudinal accumulation of RNP with regular retreatments. There remains a tremendous unmet need for pharmacotherapies that can slow RNP progression and ultimately reperfuse areas of the non-perfused retina. Towards this end, novel targets including the semaphorin family are being investigated.

Managing Neovascular Age-Related Macular Degeneration in Clinical Practice: Systematic Review, Meta-Analysis, and Meta-Regression.

The use of anti-vascular endothelial growth factor (VEGF) agents has profoundly changed the prognosis of neovascular age-related macular degeneration (nAMD). As clinical experiences have accumulated, it has become mandatory to summarize data to give information that can be useful in everyday practice. We conducted a systematic review to identify randomized controlled trials (RCTs) and observational studies that reported 12-month changes in best-corrected visual acuity (BCVA) in patients with nAMD on anti-VEGF monotherapy. Data were analyzed in a random-effects meta-analysis with BCVA change as the primary outcome. Meta-regression was conducted to evaluate the impact of multiple covariates. Four hundred and twelve heterogeneous study populations (109,666 eyes) were included. Anti-VEGFs induced an overall improvement of +5.37 ETDRS letters at 12 months. Meta-regression showed that mean BCVA change was statistically greater for RCTs (p = 0.0032) in comparison with observational studies. Populations following a proactive regimen had better outcomes than those following a reactive treatment regimen. Mean BCVA change was greater in younger populations, with lower baseline BCVA and treated with a higher number of injections (p < 0.001). Our results confirm that anti-VEGFs may produce a significant functional improvement at 12 months in patients with nAMD.

Influenza-induced thrombotic microangiopathy in a patient with cancer on proteasome inhibitor: a diagnostic dilemma.

Thrombotic microangiopathy (TMA) in a cancer patient is a common complication of either cancer itself or anticancer therapy. Incidence of TMA from anticancer therapy was found to be > 15%, since the introduction of anti-angiogenic drugs like anti-vascular endothelial growth factor agents. It is, however, important to not ignore other causes of TMA such as bacteria, viruses, antiplatelet drugs, hereditary complement mutations, and autoimmune disorders. We present such a diagnostic dilemma in our patient who was admitted with influenza and was found to have TMA on renal biopsy, while on proteasome inhibitor (PI) therapy. With this case, we would like to highlight the importance of understanding the true cause of TMA to avoid unwarranted long-term discontinuation of life saving anti-cancer drugs after TMA resolution.

Ultra-Widefield Fundus Fluorescein Angiography Findings in Patients with Fuchs' Uveitis Syndrome.

Background:The aim of this study was to evaluate ultra-widefield (UWF) fundus fluorescein angiography (FFA) findings in patients with Fuchs’ uveitis syndrome (FUS).Materials and Methods:This cross-sectional study was conducted in patients with FUS. All the patients underwent a complete ophthalmologic examination, and FFA was carried out with Optos UWF retinal imaging. Standard FFA and image acquisition consisted of early phase (15–45 s) images, and late-phase (5–10 min) images were also obtained for both eyes.Results:Forty eyes from twenty unilateral FUS patients, including 11 females (55%), who had a mean age of 38.50 ± 6.97 years, were enrolled. Eighty-five percent of the FUS eyes had optic disc hyperfluorescence (ODH) in the FFA. A significant relationship was observed between ODH and iris heterochromia (P = 0.004). ODH was seen in all the patients with iris heterochromia (n = 16). Peripheral vascular leakage (PVL), capillary nonperfusion, chorioretinal scar, and vascular sheathing were observed in 3, 3, 2, and 8 of the patients’ eyes, respectively.Conclusion:UWF FFA imaging seemed to be mandatory for evaluating the prognosis of the FUS patients, and another investigation may require to be conducted to evaluate the effect of antivascular endothelial growth factor agents for the management of PVL in these patients.

Intravitreal ranibizumab for postlaser anterior segment ischemia in retinopathy of prematurity

This case report documents the successful management of anterior segment ischemia, a very rare complication following laser in retinopathy of prematurity (ROP), by intravitreal injection of Ranibizumab, an anti-vascular endothelial growth factor agent. This is the first report as per MEDLINE search on the use and efficacy of bilateral intravitreal injection of Ranibizumab in anterior segment ischemia postlaser in ROP.

The nuclear factor E2-related factor 2 and age-related macular degeneration.

After the discovery of anti-vascular endothelial growth factor agents as treatment of wet age-related macular degeneration, the number of studies with the objective to understand the molecular mechanisms involved in the age-re lated macular degeneration genesis has increased. The importance of the nuclear factor e2-related factor 2 lies in its activation-derived proteins being involved in the maintenance of the redox balance and consequent prevention of degenerative macular disease. This article aims to present the characteristics of nuclear factor e2-related factor 2 and describe the main nuclear factor e2-related factor 2-activated antioxidant enzymes that contribute to the preservation of vision.

Topical application of TAK1 inhibitor encapsulated by gelatin particle alleviates corneal neovascularization.

Rationale: Corneal neovascularization (CoNV) is a severe complication of various types of corneal diseases, that leads to permanent visual impairment. Current treatments for CoNV, such as steroids or anti-vascular endothelial growth factor agents, are argued over their therapeutic efficacy and adverse effects. Here, we demonstrate that transforming growth factor-β (TGF-β)-activated kinase 1 (TAK1) plays an important role in the pathogenesis of CoNV.Methods: Angiogenic activities were assessed in ex vivo and in vitro models subjected to TAK1 inhibition by 5Z-7-oxozeaenol, a selective inhibitor of TAK1. RNA-Seq was used to examine pathways that could be potentially affected by TAK1 inhibition. A gelatin-nanoparticles-encapsulated 5Z-7-oxozeaenol was developed as the eyedrop to treat CoNV in a rodent model.Results: We showed that 5Z-7-oxozeaenol reduced angiogenic processes through impeding cell proliferation. Transcriptome analysis suggested 5Z-7-oxozeaenol principally suppresses cell cycle and DNA replication, thereby restraining cell proliferation. In addition, inhibition of TAK1 by 5Z-7-oxozeaenol blocked TNFα-mediated NFκB signalling, and its downstream genes related to angiogenesis and inflammation. 5Z-7-oxozeaenol also ameliorated pro-angiogenic activity, including endothelial migration and tube formation. Furthermore, topical administration of the gelatin-nanoparticles-encapsulated 5Z-7-oxozeaenol led to significantly greater suppression of CoNV in a mouse model compared to the free form of 5Z-7-oxozeaenol, likely due to extended retention of 5Z-7-oxozeaenol in the cornea.Conclusion: Our study shows the potential of TAK1 as a therapeutic target for pathological angiogenesis, and the gelatin nanoparticle coupled with 5Z-7-oxozeaenol as a promising new eyedrop administration model in treatment of CoNV.

Anti VEGF for post op CME- Boon or Bane!

Cataract surgery has advanced in techniques and instrumentation over the years, but complications such as cystoid macular edema (CME) do occur even after uneventful surgery. The incidence of pseudophakic CME (detected by optical coherence tomography) is 30%–40% after uncomplicated phaco cataract surgeries. Risk factors for the development of CME include prolonged duration of surgery, iris handling and diabetes. Corticosteroids are the mainstay of treatment of postoperative inflammation and CME. In certain situations where steroids are contraindicated anti-vascular endothelial growth factor (VEGF) agents are used as the second line agents for the treatment of CME. Here, we describe a case of postoperative uveitis with CME which showed good response with single dose intravitreal anti-VEGF injection-Bevacizumab.

POSA3 Comparative Efficacy of Anti-Vascular Endothelial Growth Factor (ANTI-VEGF) Agents for Treatment of Neovascular Age-Related Macular Degeneration (NAMD): A Systematic Review and Network Meta-Analysis

We conducted a systematic literature review (SLR) and network meta-analysis (NMA) comparing efficacy, safety and injection frequency of brolucizumab relative to other approved and marketed anti-VEGFs in nAMD patients.

Ranibizumab port delivery system in neovascular age-related macular degeneration.

Ranibizumab has proven its efficacy in various retinal diseases and particularly in neovascular age-related macular degeneration (nAMD). The number of injections and the frequent follow-up visits has been burdensome to patients particularly during the COVID era. Ranibizumab port delivery system (RPDS) seems to be a boon in prolonging the action of the drug without the need for frequent injections and follow-up visits. This review article highlights the dosage, adverse effects, and visual outcome associated with various trials of RPDS. For this article, we conducted a PubMed search and review of literature on nAMD, the incidence of AMD, anti-vascular endothelial growth factor (anti-VEGF) agents, RPDS, phase-1 trial of RPDS, phase-2 (LADDER trial) of RPDS, phase-3 (ARCHWAY trial) of RPDS, PORTAL trial of RPDS, results of phase-1 trial of RPDS, results of phase-2 (LADDER) trial of RPDS, and results of phase-3 (ARCHWAY) trial of RPDS.

The Impact of Interval between Recurrence and Reinjection in Anti-VEGF Therapy for Diabetic Macular Edema in Pro Re Nata Regimen.

Background: Pro re nata (PRN) regimen using anti-vascular endothelial growth factor (VEGF) agent is popular for the treatment of diabetic macular edema (DME). We investigated the influence of waiting time (WT) and interval between the date of recurrence of edema and re-injection on treatment efficacy. Methods: This retrospective study conducted at 7 sites in Japan enrolled patients who received intravitreal injection of ranibizumab (IVR) and aflibercept (IVA) in 1+PRN regimen. Enrolled patients were divided into 2 groups: prompt group (less than 1 week) and deferred group (3 weeks or more). Central retinal thickness (CRT) and best corrected visual acuity (BCVA) were measured every month for 1 year. Results: CRT in the deferred group was significantly higher than that in the prompt group at 2, 5, 6, 7, and 12 months (p < 0.05). BCVA in the prompt group was significantly better than that in the deferred group at 7, 10, and 12 months (p < 0.05). Conclusion: The prompt group was superior in anatomical and functional improvement of DME in anti-VEGF therapy than the deferred group. Our data suggests that shorter WT is recommended for better visual prognosis in the treatment for DME.

Predictive Biomarkers of Age-Related Macular Degeneration Response to Anti-VEGF Treatment.

Age-related macular degeneration (AMD) is an incurable disease associated with aging that destroys sharp and central vision. Increasing evidence implicates both systemic and local inflammation in the pathogenesis of AMD. Intravitreal injection of anti-vascular endothelial growth factor (VEGF) agents is currently the first-line therapy for choroidal neovascularization in AMD patients. However, a high number of patients do not show satisfactory responses to anti-VEGF treatment after three injections. Predictive treatment response models are one of the most powerful tools for personalized medicine. Therefore, the application of these models is very helpful to predict the optimal treatment for an early application on each patient. We analyzed the transcriptome of peripheral blood mononuclear cells (PBMCs) from AMD patients before treatment to identify biomarkers of response to ranibizumab. A classification model comprised of four mRNAs and one miRNA isolated from PBMCs was able to predict the response to ranibizumab with high accuracy (Area Under the Curve of the Receiver Operating Characteristic curve = 0.968), before treatment. We consider that our classification model, based on mRNA and miRNA from PBMCs allows a robust prediction of patients with insufficient response to anti-VEGF treatment. In addition, it could be used in combination with other methods, such as specific baseline characteristics, to identify patients with poor response to anti-VEGF treatment to establish patient-specific treatment plans at the first visit.

Comparative Efficacy of Pharmacotherapy for Macular Edema Secondary to Retinal Vein Occlusion: A Network Meta-analysis.

Purpose: This network meta-analysis was conducted to obtain the relative effectiveness of different pharmacotherapy of macular edema secondary to retinal vein occlusion (RVO) by summarizing all available evidences. Methods: PubMed, Embase, and Cochrane Library databases were searched for all relevant randomized controlled trials. The outcomes were estimated through a network meta-analysis, including the mean change in best-corrected visual acuity (BCVA) from baseline, the proportion of patients who gained ≥15 letters in BCVA from baseline, the mean change in central retinal thickness (CRT). Results: We identified 15 randomized controlled trials (RCTs) involving 3,431 patients with RVO in our study. Different therapeutic regimens were compared including three anti-vascular endothelial growth factor (VEGF) agents (ranibizumab, bevacizumab, and aflibercept), ranibizumab with laser, dexamethasone intravitreal implant, and laser. For branch RVO, ranibizumab 0.5 mg monthly [weighted mean difference (WMD) = 11, 95% confidence intervals (CrI) 3.6 to 19], ranibizumab 0.5 mg 3 + pro re nata (WMD = 9.4, 95% CrI 0.43–18) is most effective in terms of changes of BCVA and 15 letters or more of BCVA improvement. For central RVO, three anti-VEGF regimens can improve visual acuity and there is no significant difference of efficacy among ranibizumab, bevacizumab and aflibercept (p > 0.05). Ranibizumab 0.5 mg monthly could achieve additional efficacy in CRT reduction in eyes with branch RVO or central RVO (WMD = -130, 95% CrI -400 to 140 or WMD = -280, 95% CrI -590 to 16)). Dexamethasone intravitreal implant (WMD = 1.7, 95% CrI -4.2 to 7.1 or WMD = 0.38, 95% CrI -9.8 to 8.8)) did not show a significant improvement in visual acuity at the end of 6 months follow-up in eyes with branch RVO or central RVO. Conclusion: In summary, this network meta-analysis demonstrated several anti-VEGF agents had equivalent effects on mean visual acuity changes and anatomical recovery in 6 months in eyes with branch or central RVO. Only one injection of dexamethasone intravitreal implant in 6 months could not maintain the visual benefit. Patients and clinicians could choose pharmacotherapies with further consideration toward personal factors.

Antivascular endothelial growth factor agents for wet age-related macular degeneration: an IRIS registry analysis

ObjectifÉvaluer les stratégies thérapeutiques et les résultats obtenus chez des patients qui ont reçu un anti-VEGF (facteur de croissance endothélial vasculaire) dans le traitement de la dégénérescence maculaire liée à l’âge (DMLA) humide aux États-Unis. NatureÉtude rétrospective. ParticipantsPatients présentant une DMLA humide. MéthodesÀ l'aide du registre IRIS, nous avons étudié les patients âgés d'au moins 50 ans présentant une DMLA humide qui ont reçu au moins une injection d'anti-VEGF et pour lesquels on disposait d'un suivi d'au moins 1,5 an. Les patients ont été regroupés en fonction de la durée du suivi (en années): ≥ 1,5 an (cohorte 1), ≥ 2,5 ans (cohorte 2) et ≥ 3,5 ans (cohorte 3). RésultatsLes caractéristiques des patients étaient semblables d'un groupe à l'autre. À la fin de la 1re année, l'intervalle entre les injections était inférieur à 8 semaines pour 36,8 % des yeux sous ranibizumab, 34,5 % de ceux sous aflibercept et 39,2 % de l'ensemble des yeux traités par un anti-VEGF. Les résultats étaient semblables lors de la 2e et de la 3e année. Dans les cohortes 1–3, la variation de l'acuité visuelle (AV) par rapport aux valeurs de départ s’échelonnait de 0,3 à 0,7 lettre selon l’étude ETDRS (Early Treatment Diabetic Retinopathy Study) la 1re année, de –1,3 à –1,7 lettre la 2e année et de –2,8 à –3,1 lettres la 3e année. À la fin de la 3e année, le traitement avait été interrompu (aucune injection pendant plus de 6 mois) dans 41 % des yeux traités par le ranibizumab, 39 % de ceux sous aflibercept et 42 % de l'ensemble des yeux traités par un anti-VEGF. ConclusionÀ la fin de la 1re année, l'intervalle entre les injections était inférieur à 8 semaines dans environ le tiers des yeux. L'AV était légèrement meilleure à la fin de la 1re année pour ensuite se détériorer après la 1re année, en dépit du traitement. À la fin de la 3e année, le traitement avait été interrompu dans plus du tiers des yeux. Compte tenu du fardeau élevé associé à ce traitement, les patients qui présentent une DMLA humide pourraient bénéficier d'une démarche plus durable reposant sur un schéma d'administration moins fréquent.

GEOGRAPHIC ATROPHY INCIDENCE AND PROGRESSION AFTER INTRAVITREAL INJECTIONS OF ANTI-VASCULAR ENDOTHELIAL GROWTH FACTOR AGENTS FOR AGE-RELATED MACULAR DEGENERATION: A Meta-Analysis.

Geographic atrophy (GA) is a complication of advanced neovascular age-related macular degeneration that can lead to permanent vision loss. We sought to estimate the incidence and progression of GA after intravitreal injections of antivascular endothelial growth factor agents in eyes with neovascular age-related macular degeneration. Ovid MEDLINE, EMBASE, and Cochrane CENTRAL were searched from inception to May 2020. Included studies reported on the progression or development of GA in eyes with neovascular age-related macular degeneration after antivascular endothelial growth factor therapy. Thirty-one articles and 4,609 study eyes (4,501 patients) were included. Eyes received a mean of 17.7 injections over 35.2 months. The prevalence of GA at baseline was 9.7%. The pooled incidence of GA was 30.5% at the end of follow-up. There was a positive, moderate linear correlation between the mean total number of injections and GA incidence at the final follow-up (R2 = 0.30; P = 0.01). Monthly treatment was associated with a significantly higher risk for GA development relative to pro re nata (relative risk = 1.40, 95% confidence interval = [1.21-1.61], P < 0.001). Risk factors for GA development included GA in the fellow eye, retinal angiomatous proliferation, drusen, and reticular pseudodrusen. We found an association between the frequency and number of treatments with antivascular endothelial growth factor agents and the development of GA in neovascular age-related macular degeneration. Future studies should clarify risk factors, population characteristics, and relative contributions of treatment and disease progression on GA development in this context.

Anti-vascular endothelial growth factor therapy for age-related macular degeneration: a systematic review and network meta-analysis

BackgroundThe comparative safety and efficacy between anti-vascular endothelial growth factor agents (anti-VEGFs) and between combined therapies for patients with neovascular age-related macular degeneration (nAMD) is unclear. We conducted a systematic review to examine the comparative safety and efficacy anti-VEGFs for adults with nAMD.MethodsStudies were identified through MEDLINE, EMBASE, and Cochrane CENTRAL (inception to June 3, 2019), grey literature, and scanning reference lists. Two reviewers independently screened citations and full-text articles to identify randomized controlled trials (RCTs), extracted data, and appraised risk of bias. Pairwise random-effects meta-analysis and Bayesian network meta-analysis (NMA) were conducted. The primary outcomes were the proportion of patients experiencing moderate vision gain (≥ 15 letters on the Early Treatment Diabetic Retinopathy Study chart) and the proportion of patients experiencing moderate vision loss (≤ 15 letters).ResultsAfter screening 3647 citations and 485 potentially relevant full-text articles, 92 RCTs with 24,717 patients were included. NMA (34 RCTs, 8809 patients, 12 treatments) showed small differences among anti-VEGFs in improving the proportion of patients with moderate vision gain, with the largest for conbercept versus broluczumab (OR 0.15, 95% CrI: 0.05–0.56), conbercept versus ranibizumab (OR 0.17, 95% CrI: 0.05–0.59), conbercept versus aflibercept (OR 0.19, 95% CrI: 0.06–0.65), and conbercept versus bevacizumab (OR 0.2, 95% CrI: 0.06–0.69). In NMA (36 RCTs, 9081 patients, 13 treatments) for the proportion of patients with moderate vision loss, small differences were observed among anti-VEGFs, with the largest being for conbercept versus aflibercept (OR 0.24, 95% CrI: 0–4.29), conbercept versus brolucizumab (OR 0.24, 95% CrI: 0–4.71), conbercept versus bevacizumab (OR 0.26, 95% CrI: 0–4.65), and conbercept versus ranibizumab (OR 0.27, 95% CrI: 0–4.67).ConclusionThe only observed differences were that ranibizumab, bevacizumab, aflibercept, and brolucizumab were statistically superior to conbercept in terms of the proportion of patients with nAMD who experienced moderate vision gain. However, this finding is based on indirect evidence through one small trial comparing conbercept with placebo. This does not account for drug-specific differences when assessing anatomic and functional treatment efficacy in variable dosing regimens.Systematic review registrationPROSPERO registration number CRD42015022041.

Developments in systemic therapies for the management of lung cancer.

Lung cancer accounts for approximately 1 in 10 new cancer diagnoses annually and is responsible for the most cancer-associated deaths in Australia. Despite such figures, there is reason for optimism with many practice-changing developments to report for the management of patients with thoracic malignancies over the last few years. We outline such changes, including the emerging role of immunotherapy in the neoadjuvant and adjuvant setting for patients with localised non-small-cell lung cancer, as well as the established standard of consolidation immunotherapy following definitive chemoradiotherapy for those with locally advanced disease. In the metastatic setting, combination chemotherapy-immunotherapy approaches have become the new paradigm for most patients in the absence of a recognised driver mutation. A range of novel targeted therapies now exist and are Pharmaceutical Benefits Scheme (PBS)-subsidised for targets such as EGFR, ALK and ROS1, with many others, such as KRAS G12C, NTRK, MET, RET and HER2, also with therapies rapidly being developed. Even among patients with small-cell lung cancer, who account for the worst prognoses and until recently have received a chemotherapy regimen that has remained unchanged in over 20 years, there is a new standard-of-care in combination chemotherapy-immunotherapy. Furthermore, immunotherapy and potentially anti-vascular endothelial growth factor agents now also play a role in mesothelioma treatment. Last, given recent developments in immunotherapy, targeted therapy and combination approaches in the non-small-cell lung cancer space, there is an increasing recognition of the diversity of lived experience for such patients and need for survivorship programmes to acknowledge such nuances.

Short-term changes in retinal and choroidal relative flow volume after anti-VEGF treatment for neovascular age-related macular degeneration

The effects of anti-vascular endothelial growth factor (anti-VEGF) agents on the native ocular vasculature are poorly understood. This pilot study aimed to assess short-term changes in retinal and choroidal perfusion after anti-VEGF treatment for neovascular exudative age-related macular degeneration (nAMD) using the relative flow volume (RFV) parameter derived from laser speckle flowgraphy. Ten treatment-naïve nAMD patients underwent measurements of mean, maximum, minimum, and differential RFV within a retinal arteriolar segment and a choroidal vessel segment outside the neovascular area. Measurement of retinal RFV (rRFV), choroidal RFV (cRFV), and subfoveal choroidal thickness (SCT) was repeated 9 and 35 days after a single anti-VEGF injection. The treatment caused a statistically significant decrease in the mean rRFV, mean cRFV, and SCT during the follow-up (p < 0.05). At the intermediate visit, the mean cRFV and SCT were − 17.6% and − 6.4% compared to baseline, respectively. However, at the final measurement, the mean cRFV was not different from the baseline value, which indicated waning of the anti-VEGF effect. In conclusion, a single anti-VEGF injection in treatment-naïve nAMD resulted in a decrease in retinal arteriolar and choroidal perfusion, according to the RFV parameter, which is a promising tool to simultaneously assess retinal and choroidal perfusion changes in response to anti-VEGF therapy.

Correlation of Change in Central Subfield Thickness and Change in Visual Acuity in Neovascular AMD: Post Hoc Analysis of VIEW 1 and 2

Determine correlation between change in central subfield thickness (CST) and change in best-corrected visual acuity (BCVA) in neovascular age-related macular degeneration receiving anti-vascular endothelial growth factor agents. A post hoc analysis of VIEW 1 and 2 randomized clinical trials. This analysis included participants randomized to ranibizumab 0.5 mg every 4 weeks (Rq4), intravitreal aflibercept injection 2 mg every 4 weeks (2q4), and intravitreal aflibercept injection 2 mg every 8 weeks after 3 monthly doses (2q8) to week 52, followed by capped as-needed (at least every 12 weeks) dosing to week 96. Relationship between changes in CST and BCVA was determined using Pearson correlation coefficient. Of 1815 eyes, 595 were assigned to the Rq4, 613 to 2q4, and 607 to 2q8 arms. Correlations (95% confidence intervals [CI]) at weeks 12, 52, and 96 were -0.08 (95% CI, -0.17 to 0.00), -0.05 (95% CI, -0.14 to 0.04), and -0.15 (95% CI, -0.24 to -0.06) for Rq4; -0.13 (95% CI, -0.21 to -0.04), -0.06 (95% CI, -0.14 to 0.03) and -0.04 (95% CI, -0.13 to 0.05) for 2q4, and -0.04 (95% CI, -0.12 to 0.05), -0.01 (95% CI, -0.09 to 0.08), and -0.01 (95% CI, -0.10 to 0.09) for 2q8. Linear regression analysis adjusted for relevant baseline factors showed CST changes accounted for 11% of BCVA changes. Every 100 μm decrease in CST was associated with a 0.3 letter decrease (P = .25) at week 52 and a 0.14 letter decrease (P = .69) at week 96. Weak or no correlation was found between changes in CST and BCVA with either agent or regimen, suggesting changes in CST should not be used as a surrogate for visual acuity outcomes in neovascular age-related macular degeneration.

Safety Outcomes of Brolucizumab in Neovascular Age-Related Macular Degeneration

Limited data exist on the real-world safety outcomes of patients with neovascular age-related macular degeneration treated with brolucizumab (Beovu). To determine the real-world incidence of intraocular inflammation (IOI), including retinal vasculitis (RV) and/or retinal vascular occlusion (RO), for patients with neovascular age-related macular degeneration who underwent brolucizumab treatment. Additionally, potential risk factors associated with these adverse events were evaluated. This cohort study included patients with neovascular age-related macular degeneration in the Intelligent Research in Sight (IRIS) Registry and Komodo Healthcare Map. Patients initiating and receiving 1 or more brolucizumab injections from October 8, 2019, to June 5, 2020, with up to 6 months of follow-up were included. Brolucizumab injections. Incidence of IOI (including RV) and/or RO and RV and/or RO and risk stratification for the identified risk factors. Of 10 654 and 11 161 included eyes (from the IRIS Registry and Komodo Health database, respectively), the median follow-up times were 97 and 95 days. Most eyes switched from another anti-vascular endothelial growth factor agent (9686 of 10 654 [90.9%] and 10 487 of 11 161 [94.0%], respectively), most commonly aflibercept (7160 of 9686 [73.9%] and 7156 of 10 487 [68.2%]), and most were from women (6105 of 10 654 [57.3%] and 6452 of 11 161 [57.8%]). The overall incidence of IOI and/or RO was 2.4% (255 of 10 654 eyes) and 2.4% (268 of 11 161 eyes) for the IRIS and Komodo groups, respectively, and RV and/or RO, 0.6% (59 of 10 654 eyes and 63 of 11 161 eyes), respectively. Patients with a history of IOI and/or RO in the 12 months before brolucizumab initiation had an increased observed risk rate (8.7% [95% CI, 6.0%-11.4%] and 10.6% [95% CI, 7.5%-13.7%]) for an IOI and/or RO event in the 6 months following the first brolucizumab treatment compared with patients without prior IOI and/or RO (2.0% in both data sets). There was an increased estimated incidence rate in women (2.9% [95% CI, 2.5%-3.3%] and 3.0% [95% CI, 2.6%-3.4%]) compared with men (1.3% [95% CI, 1.0%-1.7%] and 1.4% [95% CI, 1.0%-1.7%]), but this risk was not as large as that of a prior IOI and/or RO. Similar findings were observed for patients with RV and/or RO events. The incidence rate of IOI and/or RO was approximately 2.4%. Patient eyes with IOI and/or RO in the 12 months prior to first brolucizumab injection had the highest observed risk rate for IOI and/or RO in the early months after the first brolucizumab treatment. However, given study limitations, the identified risk factors cannot be used as predictors of IOI and/or RO events, and causality with brolucizumab cannot be assessed.