Intravitreal anti-VEGF Therapy Research Articles

Investigation of choroidal structure changes after intravitreal anti-VEGF therapy for retinal vein occlusion.

We aimed to investigate the effect of retinal vein occlusion (RVO) on the posterior segment structures of the eye and its changes with intravitreal anti-Vascular Endothelial Growth Factor (VEGF) treatment. This prospective longitudinal study included 29 eyes of 29 patients with RVO (17 males and 12 females) followed for 6 months. The best corrected visual acuity (BCVA), macula, choroid ticknesses and choroidal vascularity index (CVI) obtained by spectral-domain optical coherence tomography were recorded at baseline and the first, third, and sixth months after the first injection. Results were compared with fellow eyes (non-affected eyes) and age- and sex-matched controls. BCVA increased significantly in the 6th month, more in the first month of injection (p < 0.05 for each). Central macular tickness, subfoveal choroid tickness, stromal and total area of choroid decreased significantly after injection (p < 0.05 for each). CVI values increased significantly, especially in the 1st month after injection (p < 0.05 for each). In eyes with Branch RVO, there was a significant decrease in the macular thickness of the occlusive areas with treatment, while there was no statistically significant change in the non-occlusive macular thickness. Observation of changes in choroidal structure may be useful to assess the activity of RVO and predict the efficacy of anti-VEGF therapy.

Cardiovascular and cerebrovascular adverse events associated with intravitreal anti-vascular endothelial growth factor monoclonal antibodies: a World Health Organization pharmacovigilance study

PurposeTo analyze cardiovascular and cerebrovascular adverse events (ADRs) after intravitreal anti-vascular endothelial growth factor (VEGF; aflibercept, bevacizumab, brolucizumab, and ranibizumab) treatment. SubjectsVigiBase, a World Health Organization (WHO) global safety report database DesignPharmacovigilance study MethodsThe individual-case-safety reports (ICSR) of cardiovascular and cerebrovascular ADRs after intravitreal anti-VEGF treatment were compared with those reported in the full database. From 2004 to 2023, 23,129 ADRs after intravitreal anti-VEGF therapy and 25,015,132 ADRs associated with any drug (full database). Main Outcome MeasuresThe reporting odds ratio (ROR) and information components (IC) were calculated, and the 95% lower credibility interval endpoint of the information component (IC025) was used for disproportionate Bayesian reporting. Inter-drug comparisons were performed using the ratio of odd ratio (rOR). ResultsCompared with the full database, anti-VEGFs were associated with an increased reporting of myocardial infarction (IC025 0.75; ROR: 1.78 [95% CI 1.70–1.86]), angina pectoris (IC025 0.53; ROR: 1.61 [95% CI 1.47–1.77]), arrythemias including atrial fibrillation, atrial flutter, ventricular fibrillation, supraventricular tachycardia (all IC025 >0, ROR>1), hypertension (IC025 2.22; ROR: 4.91 [95% CI 4.82–5.01]), and hypertensive crisis (IC025 1.97; ROR: 4.49 [95% CI 4.07–4.97]). Moreover, anti-VEGFs were associated with a higher reporting of cerebrovascular ADRs such as cerebral infarction (IC025 4.34; ROR: 23.19 [95% CI 22.10–24.34]), carotid artery stenosis (IC025 1.85; ROR: 5.24 [95% CI 3.98–6.89]), cerebral hemorrhage (IC025 2.29; ROR: 5.38 [95% CI 5.03–5.76]), and subarachnoid hemorrhage (IC025 1.98; ROR: 4.81 [95% CI 4.14–5.6]). Inter-drug comparison indicated that compared to ranibizumab, patients with aflibercept showed overall under-reporting of cardiovascular and cerebrovascular ADRs such as myocardial infarction (rOR 0.55 [95% CI 0.49–0.52]), atrial fibrillation (rOR 0.28 [95% CI 0.23–0.35]), cerebrovascular accident (rOR, 0.15 [95% CI 0.14–0.17]), and cerebral hemorrhage (rOR, 0.51 [95% CI 0.40–0.65]). ConclusionsIn this pharmacovigilance case-noncase study, significantly increased reporting of cardiovascular and cerebrovascular ADRs were identified after intravitreal anti-VEGF treatment. While ranibizumab may exhibit superior systemic safety regarding its biological characteristics, it is crucial not to overlook the occurrence of cardiovascular and cerebrovascular ADRs considering its higher reporting rate than bevacizumab or aflibercept.

International Classification System for Ocular Complications of Anti-VEGF Agents in Clinical Trials

Complications associated with intravitreal anti-VEGF therapies are reported inconsistently in the literature, thus limiting an accurate evaluation and comparison of safety between studies. This study aimed to develop a standardized classification system for anti-VEGF ocular complications using the Delphi consensus process. Systematic review and Delphi consensus process. Twenty-five international retinal specialists participated in the Delphi consensus survey. A systematic literature search was conducted to identify complications of intravitreal anti-VEGF agent administration based on randomized controlled trials (RCTs) of anti-VEGF therapy. A comprehensive list of complications was derived from these studies, and this list was subjected to iterative Delphi consensus surveys involving international retinal specialists who voted on inclusion, exclusion, rephrasing, and addition of complications. Furthermore, surveys determined specifiers for the selected complications. This iterative process helped to refine the final classification system. The proportion of retinal specialists who choose to include or exclude complications associated with anti-VEGF administration. After screening 18 229 articles, 130 complications were categorized from 145 included RCTs. Participant consensus via the Delphi method resulted in the inclusion of 91 complications (70%) after 3 rounds. After incorporating further modifications made based on participant suggestions, such as rewording certain phrases and combining similar terms, 24 redundant complications were removed, leaving a total of 67 complications (52%) in the final list. A total of 14 complications (11%) met exclusion thresholds and were eliminated by participants across both rounds. All other remaining complications not meeting inclusion or exclusion thresholds also were excluded from the final classification system after the Delphi process terminated. In addition, 47 of 75 proposed complication specifiers (63%) were included based on participant agreement. Using the Delphi consensus process, a comprehensive, standardized classification system consisting of 67 ocular complications and 47 unique specifiers was established for intravitreal anti-VEGF agents in clinical trials. The adoption of this system in future trials could improve consistency and quality of adverse event reporting, potentially facilitating more accurate risk-benefit analyses. Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Long-term dynamic changes and influencing factors of corneal morphology after multiple intravitreal injections of anti-VEGF drugs.

To observe alterations in corneal morphology caused by repeated intravitreal injections of anti-vascular endothelial growth factor (VEGF). Prospective cohort study. Seventy-seven eyes were treated with intravitreal injection of anti-VEGF from June 2021 to March 2023. There were 25 eyes of neovascular age-related macular degeneration (nAMD), 24 eyes of diabetic macular edema (DME), and 28 eyes of retinal vein occlusion (RVO). Aflibercept was used in 37 eyes and Ranibizumab was used in 40 eyes. 3 + PRN was used. Corneal endothelium and corneal thickness were measured using a corneal endothelial microscope. The data related to central corneal thickness, corneal endothelial cell density (ECD), average cell size, coefficient of variation (CV), proportion of hexagonal cells (Hex%) was collected. A comparison was also made between baseline and the dynamic changes of all indexes 1 year following the last injection. It was observed that in comparison to baseline, ECD and Hex% decreased significantly after the 3rd injection of Aflibercept and Ranibizumab. However, ECD did not decrease further and remained at the same level as after the last injection. Hex% and average cell size increased to a certain extent in comparison to the last injection. All the changes were found to be statistically significant (P < .01). After 3 injections, ECD in DME group was markedly lower than that in nAMD and RVO group, but the CV in DME group was higher than that in nAMD as well as RVO groups, and all the differences were statistically significant (P < .05). Following intravitreal anti-VEGF therapy, DME is more likely than other disorders to result in a decrease in ECD. Repeated intravitreal injections of anti-VEGF drugs can reduce the Hex% and ECD to a certain extent. After the last injection, Hex% can progressively recover, and ECD can remain stable without further declining. After injections, ECD in DME group was found to be significantly lower than that in nAMD and RVO groups, but CV in DME group was significantly higher in comparison to the other 2 groups. In patients with macular edema, repeated intravitreal injections of anti-VEGF may have certain effects on corneal morphology. Patients with diabetes mellitus in particular should pay special attention to corneal safety following repeated intravitreal injections if they have significantly reduced ECD at baseline.

Exploring the Impact of Saccharin on Neovascular Age-Related Macular Degeneration: A Comprehensive Study in Patients and Mice.

We aimed to determine the impact of artificial sweeteners (AS), especially saccharin, on the progression and treatment efficacy of patients with neovascular age-related macular degeneration (nAMD) under anti-vascular endothelial growth factor (anti-VEGF-A) treatment. In a cross-sectional study involving 46 patients with nAMD undergoing intravitreal anti-VEGF therapy, 6 AS metabolites were detected in peripheral blood using liquid chromatography - tandem mass spectrometry (LC-MS/MS). Disease features were statistically tested against these metabolite levels. Additionally, a murine choroidal neovascularization (CNV) model, induced by laser, was used to evaluate the effects of orally administered saccharin, assessing both imaging outcomes and gene expression patterns. Polymerase chain reaction (PCR) methods were used to evaluate functional expression of sweet taste receptors in a retinal pigment epithelium (RPE) cell line. Saccharin levels in blood were significantly higher in patients with well-controlled CNV activity (P = 0.004) and those without subretinal hyper-reflective material (P = 0.015). In the murine model, saccharin-treated mice exhibited fewer leaking laser scars, lesser occurrence of bleeding, smaller fibrotic areas (P < 0.05), and a 40% decrease in mononuclear phagocyte accumulation (P = 0.06). Gene analysis indicated downregulation of inflammatory and VEGFR-1 response genes in the treated animals. Human RPE cells expressed taste receptor type 1 member 3 (TAS1R3) mRNA and reacted to saccharin stimulation with changes in mRNA expression. Saccharin appears to play a protective role in patients with nAMD undergoing intravitreal anti-VEGF treatment, aiding in better pathological lesion control and scar reduction. The murine study supports this observation, proposing saccharin's potential in mitigating pathological VEGFR-1-induced immune responses potentially via the RPE sensing saccharin in the blood stream.

Cardiovascular Outcomes with Intravitreal Anti-Vascular Endothelial Growth Factor Therapy in Patients with Diabetes: A Real-World Data Analysis.

Anti-vascular endothelial growth factor (anti-VEGF) therapy is commonly used intravitreally for diabetic proliferative retinopathy, but when used systemically for treating cancers, an excess of cardiovascular disease (CVD) events has been noted. The latter is of concern for people with diabetes, who are at higher risk of CVD. This study aims to explore the relationship between incident CVD and intravitreal anti-VEGF therapy in patients with diabetes, compared to other therapies, using a large real-world global federated dataset. Data were analysed using TriNetX, a global electronic medical real-world ecosystem. The study included adults with diabetes and excluded those with a history of CVD prior to the time window of data extraction. Patients were categorised into two cohorts: anti-VEGF therapy or control cohort (laser or steroid therapies). The cohorts were 1:1 propensity score-matched for age, sex, ethnicity, body mass index, systolic blood pressure, HbA1c, and cardiovascular medications. Outcomes analysed at 1, 6 and 12months were: (1) mortality; (2) acute myocardial infarction (MI); (3) cerebral infarction; and (4) heart failure. Relative risk analyses were performed using the built-in R statistical computing platform on TriNetX. In patients with diabetes (n = 2205; mean age 58.8 ± 15.8, Stddiff 0.05; 56% male), anti-VEGF therapy was associated with a numerical but non-statistically significant increased CVD risk over 1, 6, and 12months: Mortality over 1month (RR 1; 95%CI 0.42, 2.40), 6months (RR 1.46; 95%CI 0.72, 2.95) and 12months (RR 1.41; 95%CI 0.88, 2.27). There was no excess of acute MI over 1 (RR n/a: not applicable; 0/0: 0 events in the anti-VEGF group/0 events in the control group), 6 and 12months (RR n/a; 0/10 events); cerebral infarction over 1, 6months (RR n/a; 0/0 events), and 12months (RR n/a; 0/10); and heart failure over 1month (RR n/a; 0/0 events), 6months (RR 1; 95%CI 0.42, 2.40) and 12months (RR 1; 95%CI 0.42, 2.34). There was no statistically significant risk of cardiovascular-related events in the short or medium term in patients with diabetes who received intravitreal anti-VEGF therapy, despite a small increase in the number of CVD events. Our study supports the real-world safety of intravitreal anti-VEGF therapy in patients with diabetes free of baseline CVD.

Impact of intravitreal anti-VEGF therapy on intraretinal microvascular abnormalities in proliferative diabetic retinopathy.

Impact of intravitreal anti-VEGF therapy on intraretinal microvascular abnormalities in proliferative diabetic retinopathy.

FROM DRUSEN TO TYPE 3 MACULAR NEOVASCULARIZATION.

To investigate the imaging features preceding the occurrence of type 3 (T3) macular neovascularization (MNV) using tracked spectral-domain optical coherence tomography. From a cohort of eyes with T3 MNV and ≥ 12 months of previously tracked spectral-domain optical coherence tomography, T3 lesions that developed above soft drusen were selected for optical coherence tomography analysis. Retinal imaging findings at the location where type T3 MNV occurred were analyzed at each follow-up until the onset of T3 MNV. The following optical coherence tomography parameters were assessed: drusen size (height and width), outer nuclear layer/Henle fiber layer thickness at the drusen apex, and the presence of intraretinal hyperreflective foci, retinal pigment epithelium disruption, incomplete retinal pigment epithelium and outer retina atrophy, and complete retinal pigment epithelium and outer retina atrophy. From a cohort of 31 eyes with T3 MNV, T3 lesions developed above soft drusen in 20 eyes (64.5%). Drusen showed progressive growth ( P < 0.001) associated with outer nuclear layer/Henle fiber ( P < 0.001) thinning before T3 MNV. The following optical coherence tomography features were identified preceding the occurrence of T3 MNV, typically at the apex of the drusenoid lesion: disruption of the external limiting membrane/ellipsoid zone and/or the retinal pigment epithelium, hyperreflective foci, and incomplete retinal pigment epithelium and outer retina atrophy/complete retinal pigment epithelium and outer retina atrophy. The results demonstrate specific anatomic alterations preceding the occurrence of T3 MNV that most commonly originates above soft drusen. Drusen growth, reduced outer nuclear layer/Henle fiber thickness, and retinal pigment epithelium atrophy at the drusen apex precede the development of T3 MNV. Identifying these optical coherence tomography features should warrant close monitoring for identification of T3 MNV, which can benefit from prompt intravitreal anti-vascular endothelial growth factor therapy.

Effect of Needle Gauge Size on Pain During Intravitreal Anti-VEGF Injection: A Systematic Review and Network Meta-Analysis.

Concerns related to pain from intravitreal injections are one of the key factors mentioned by patients when asked about therapy. In this systematic review and network meta-analysis, we evaluate the literature of comparative clinical trials on the relationship between needle gauge size and pain experience during intravitreal anti-vascular endothelial growth factor (anti-VEGF) therapy. We searched 12 literature databases on 14 October 2023 for comparative studies of gauge sizes for intravitreal anti-VEGF injections. The primary outcome of interest was the reported pain experience immediately after the injection. All outcomes of pain were transformed into standardized effect sizes using Cohen's d. Using a network meta-analysis approach, we were able to compare all gauge sizes and rank them according to the reported pain experience. We identified nine eligible studies with data on a total of 998 patients and 1004 eyes. Needle sizes studied were 26-gauge, 27-gauge, 29-gauge, 30-gauge, 32-gauge, 33-gauge, and 34-gauge. A complete network was present, which allowed for a network meta-analysis. We used the thickest (26-gauge) needle as the reference group and observed a clear trend of lower pain experience with thinner gauge sizes (d: -0.4, d: -2.7, d: -3.8, d: -4.8, d: -4.5, and d: -5.3; respectively, for 27-gauge, 29-gauge, 30-gauge, 32-gauge, 33-gauge, and 34-gauge). A gauge size of 30 or thinner may minimize patient discomfort related to intravitreal anti-VEGF therapy.

A study of the relationship between cytokine levels and the response to anti-VEGF therapy in polypoid choroidal vasculopathy with different choroidal thicknesses.

Polypoidal choroidal vasculopathy (PCV) is an irreversible retinal choroidal disease. Individuals with PCV exhibit diverse baseline characteristics, including systemic characteristics, ocular traits, metabolic factor levels, and different responses to intravitreal anti-VEGF therapy. This study aims to investigate the pathogenesis of PCV by analyzing the systemic characteristics, ocular traits, and cytokine levels at baseline within a cohort of patients who exhibit different responses to anti-VEGF treatment. We conducted a retrospective analysis involving 80 eyes diagnosed with PCV. Patients were categorized into two groups based on responses to suboptimal intravitreal ranibizumab injection therapy: those with suboptimal responses and optimal responses. Aqueous humor samples were collected from the experimental eyes, and cytokine expression levels were assessed using cytometric bead array analysis. All subjects were further stratified into two groups according to the median choroidal thickness. Subsequently, logistic regression analysis and the ROC curve were employed to examine the relationship between cytokine expression levels, choroidal thickness, and anti-VEGF response. The results revealed that compared to the group of optimal anti-VEGF response, the choroid in the suboptimal response group exhibited a significantly greater thickness. Additionally, compared to the suboptimal anti-VEGF response group, the expression levels of VEGF and VCAM-1 were markedly lower observed in the optimal anti-VEGF response group, while TNF-α showed the opposite trend. Logistic regression analysis indicated that VEGF, VCAM-1, and TNF-α in the aqueous humor were independent risk factors for a suboptimal anti-VEGF response. After adjusting other risk factors, the risk of suboptimal anti-VEGF response decreased to 0.998-fold, 0.997-fold, and 1.294-fold. The AUC values for VEGF, VCAM-1, and TNF-α were determined to be 0.805, 0.846, and 0.897, respectively. Furthermore, the risk of VEGF, VCAM-1, and TNF-α were significantly associated with an increased risk of suboptimal anti-VEGF response after correction for risk factors in the thick choroid group. Our study demonstrated that PCV exhibits systemic and ocular characteristics variations based on different anti-VEGF responses. The levels of cytokines in aqueous humor were found to have a significant correlation with the anti-VEGF response in PCV. VEGF, VCAM-1, and TNF-α are potential targets for assessing treatment response in thick choroidal PCV.

Regression of Neovascularization after Panretinal Photocoagulation Combined with Anti-VEGF Injection for Proliferative Diabetic Retinopathy-A Review.

Proliferative diabetic retinopathy (PDR) poses a significant therapeutic problem that often results in severe visual loss. Panretinal photocoagulation (PRP) has long been a mainstay treatment for this condition. Conversely, intravitreal anti-VEGF therapy has served as an alternative treatment for PDR. This review aimed to evaluate the effects of PRP combined with anti-VEGF therapy on the regression of neovascularization (NV), including functional outcomes and incidence of complications. The MEDLINE database was searched for articles evaluating regression of NV using a combination of the following terms: "proliferative diabetic retinopathy", "anti-VEGF", "panretinal photocoagulation", and "combined treatment". The search yielded a total of 22 articles. The analysis of their results indicated PRP combined with ant-VEGF therapy as superior over PRP alone in the management of PDR. Combination treatment yields better and faster regression of NV and a lower incidence of serious complications, such as vitreous hemorrhage and the need for pars plana vitrectomy. Nevertheless, complete regression of NV is not achieved in a significant proportion of patients. Further research is needed to establish the most effective schedule for intravitreal injections as an adjunct to PRP. The current literature shows that in some cases, cessation of anti-VEGF injection in combination treatment for PDR can lead to relapse of NV.

Intravitreal anti-vascular endothelial growth factor therapy for retinal diseases in Norway from 2011 to 2021: A combined registry and survey study.

To investigate the use of intravitreal anti-vascular endothelial growth factor (anti-VEGF) therapy in Norway from 2011 to 2021 and explore how the eye departments organized their injection services. We combined data from the Norwegian Patient Registry (NPR) with survey responses from Norway's 22 eye departments. The NPR data encompassed all registered intravitreal injection episodes from 2011 to 2021. The survey contained questions about local treatment practices and emphasized neovascular age-related macular degeneration (nAMD), retinal vein occlusion and diabetic macular edema. A total of 47247 unique patients received 841 646 intravitreal injections in the study period. The number of patients per year increased from 6522 in 2011 to 20 635 in 2021. The number of injections per year increased from 30 926 in 2011 to 125 258 in 2021. The most frequent diagnosis was nAMD. In 2021, the age-adjusted treatment activity in Norway's 11 counties ranged from 47.8 to 75.5 injections per 1000 inhabitants aged ≥50 years. The use of aflibercept gradually exceeded bevacizumab, but the aflibercept proportion per county ranged from 38 to 82% in 2021. The survey revealed varying treatment practices, local guidelines were often absent, and only half of the departments defined a lower visual limit for initiating or maintaining treatment. The use of intravitreal anti-VEGF therapy increased considerably from 2011 to 2021, but there was considerable regional variation in treatment activity, drug utilization and organization of injection services. These findings emphasize the need for strengthened governance and national guidelines to ensure equal treatment nationally.

Incidence of Total Blindness After Central Retinal Artery Occlusion With Ocular Neovascularization

Purpose: To determine the time-based incidence of total blindness after central retinal artery occlusion (CRAO) with secondary ocular neovascularization (ONV). Methods: In this retrospective cohort study, electronic records were queried using ICD-9 and ICD-10 codes to identify patients with secondary ONV post-CRAO. Patients with possible alternative ONV etiologies, previous panretinal photocoagulation (PRP), and/or previous antivascular endothelial growth factor (anti-VEGF) therapy were excluded. Clinical data included demographics, medical comorbidities, ONV manifestations, medical/surgical management, and best-corrected visual acuity (BCVA). Kaplan-Meier analysis was performed with total blindness (defined as a BCVA of no light perception) as the outcome of interest. Results: Of 345 eyes with CRAO, 34 met the inclusion criteria with a mean (±SD) follow-up of 22.0 ± 26.2 months. ONV management included PRP (70.6%), glaucoma drainage implant surgery or transscleral cyclophotocoagulation (32.4%), and intravitreal anti-VEGF therapy (mean 2.8 ± 5.6 injections per patient). The cumulative incidence of total blindness was 49.4% (95% confidence interval, 27.2%-71.6%) at 24 months, with 53.3% of cases occurring within 4 months of ONV onset. Conclusions: Post-CRAO ONV is associated with a high risk for progression from severe vision loss to total blindness. Neovascular glaucoma can present up to 4 months after CRAO, challenging the paradigm of “30-day-glaucoma.” Routine gonioscopy should extend through this period, while glaucoma surgery can delay further vision loss. These findings can be used to counsel patients on the importance of follow-up adherence.

Retraction of cystoid macular edema from the fovea after intravitreal anti-VEGF therapy for birdshot chorioretinopathy.

To report the effect of anti-vascular endothelial growth factor inhibitor (anti-VEGF) on fovea-involving cystoid macular edema in a patient with Birdshot chorioretinopathy. A 42-year-old male patient presented to our hospital with bilateral posterior uveitis with retinal vasculitis, cystoid macular edema and optic disc edem a. He was diagnosed with birdshot chorioretinopathy based on clinical appearance and tissue type HLA-A29. The patient underwent vitrectomy in the right eye without any change in visual acuity. Retinal leakage was reduced by oral prednisolone, which could not be tapered below 50 mg per day without relapse. Oral prednisolone, topical dexamethasone and subtenonal kenalog were associated with intraocular pressure rise in both eyes. Hence, his uveitis responded to steroids, but there was no detectable effect of any steroid-sparing immunomodulatory drugs. The patient had been on oral prednisolone 50 mg for five years when it was decided to attempt intravitreal VEGF inhibitor injection therapy. The anti-VEGF therapy diminished cystoid macular edema in the fovea and improved the visual acuity. Here we report for the first time the long-term outcomes of anti-VEGF injections on fovea-involving cystoid macular edema in Birdshot chorioretinopathy to keep steroid at the minimal possible doses and preserve a satisfying visual acuity level.

Current Treatment Approaches for Vascular Tumors of the Retina and Optic Disc

The vascular tumors of the retina and optic disc include retinal hemangioblastoma (capillary hemangioma), retinal cavernous hemangioma, retinal racemose hemangioma (Wyburn-Mason Syndrome) and retinal vasoproliferative tumor. Although retinal vascular tumors are not common, in some cases they can lead to diagnostic and therapeutic challenges. Sector laser photocoagulation, cryotherapy, transpupillary thermotherapy, photodynamic therapy, intravitreal anti-vascular endothelial growth factor (anti-VEGF) therapy, plaque radiotherapy, and endoresection procedures are commonly in the treatment of retinal hemangioblastoma. Cryotherapy, transpupillary thermotherapy, photodynamic therapy, intravitreal anti-VEGF therapy and dexamethasone implants, plaque radiotherapy, and endoresection methods can be applied in retinal vasoproliferative tumor. No treatment in usually necessary in retinal cavernous and racemous hemangiomas.

Maintenance of Vision Needed to Drive after Intravitreal Anti-VEGF Therapy in Patients with Neovascular Age-related Macular Degeneration and Diabetic Macular Edema

To evaluate the association between intravitreal anti-VEGF therapy and visual acuity (VA)/driving vision maintenance over 4 years in patients with neovascular age-related macular degeneration (nAMD) or diabetic macular edema (DME). Retrospective, observational, clinical practice cohort study using data from the Vestrum Health database. Initial diagnosis (January 1, 2014 to June 30, 2019) of nAMD or DME and ≥ 1 year of treatment/follow-up history. The VA analysis required 4 years of treatment/follow-up history. For the driving vision maintenance analysis, patients required Snellen VA of 20/40 or better at baseline and for ≥ 6 months during year 1 after index intravitreal anti-VEGF treatment in the better-seeing eye. A loss-of-driving event was the first clinic visit with VA worse than 20/40 sustained for ≥ 6 consecutive months. Kaplan-Meier analyses estimated the probability of maintaining driving vision over 4 years stratified by year-1 injection number. Cox proportional hazard models examined associations between baseline clinical characteristics and year-1 injection frequency and the risk of losing driving vision. Mean change in VA over time and by baseline VA, driving vision maintenance probability over time and stratified by anti-VEGF injection frequency, and baseline factors predictive of driving vision maintenance. In year 1, the nAMD and DME cohorts gained 8.5 and 9.5 ETDRS letters, respectively. Between years 1 and 4, patients with nAMD and DME lost 6.6 and 2.7 ETDRS letters, respectively. The probability of maintaining driving vision over 4 years was 56% (nAMD) and 72% (DME); among patients who received 1 to 5, 6 to 7, and ≥ 8 anti-VEGF injections in year 1, corresponding probabilities were 50%, 56%, and 65% (nAMD; P < 0.001) and 63%, 72%, and 77% (DME; P < 0.001). Baseline factors associated with driving vision loss included older age, worse index VA, geographic atrophy (nAMD), and worsening baseline diabetic retinopathy (DME). Older age and worse index VA were risk factors for driving vision loss, whereas a greater year-1 injection number was associated with driving vision maintenance through year 4, supporting early initiation and frequent anti-VEGF injections for maintaining driving vision in nAMD or DME. Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Risk of renal damage associated with intravitreal anti-VEGF therapy for diabetic macular edema in routine clinical practice.

Vascular endothelial growth factor inhibitors (anti-VEGF) have been shown to be effective in the treatment of diabetic macular edema. However, there is little information about the systemic effects of intraocular administration of anti-VEGF drugs in patients with coexistent diabetic nephropathy because it can produce adverse renal effects. This retrospective cohort study analyzed the effect of intravitreal anti-VEGF drugs (bevacizumab, ranibizumab, or aflibercept) on eFGR and microalbuminuria (MicA) in patients with diabetic macular edema and nonproliferative retinopathy without chronic kidney disease (CKD). Sixty-six patients were included, 54.5% male and 45.5% female, with a mean age of 66.70 ± 11.6 years. The mean follow-up of patients with antiangiogenic treatment was 42.5 ± 28.07 months, and the mean number of injections was 10.91 ± 7.54. In 12.1% of the cases, there was a worsening of the glomerular filtration rate (eFGR) and a 19.7% worsening of the microalbuminuria (MicA). The number of injections was not related to the worsening of the eFGR (P = 0.74) or the MicA (P = 0.239). No relationship was found between the type of drug and the deterioration of the GFR (P = 0.689) or the MicA (P = 0.53). Based on the results, there is a small proportion of patients with increase in MicA and the decrease in eFGR after anti-VEGF therapy, and these was no associated with the number of injection or the drug type. Ophthalmologists should be aware of renal damage in order to do a close monitoring of renal function and proteinuria after intravitreal administration of anti-VEGF mainly in hypertensive patients.

Brolucizumab for recalcitrant macular neovascularization in age-related macular degeneration with pigment epithelial detachment.

To analyze anatomic and functional response to intravitreal brolucizumab in age-related macular degeneration recalcitrant to previous intravitreal anti-VEGF therapies. In this monocentric, one arm, retrospective study, eyes affected by neovascular age-related macular degeneration (nAMD) resistant to other intravitreally injected anti-vascular endothelial growth factor inhibitors were switched to intravitreal brolucizumab. All patients underwent ophthalmological examinations at baseline and in regular follow-up intervals. Best registered visual acuity (BRVA), Goldmann tonometry, intraocular pressure (IOP), central retinal thickness (CRT) and pigment epithelial detachment (PED) characteristics were analyzed at initiation of anti-VEGF treatment, at treatment switch, and at the end of brolucizumab loading phase. The study included 20 eyes of 18 consecutively treated patients (age: 77 ± 6 years). All eyes had macular neovascularization with PED. Previous treatments included intravitreal aflibercept, bevacizumab, and ranibizumab and had not resulted in a significant improvement in BRVA (0.5 ± 0.5 logMAR vs 0.5 ± 0.6 logMAR) or mean CRT (320 ± 60 µm vs 313 ± 83 µm) up to treatment switch to brolucizumab. At the end of the brolucizumab loading phase, there was significant improvement for both BRVA (0.3 ± 0.2 logMAR, P < 0.05) and CRT (264 ± 55 µm, P < 0.05). Under previous anti-VEGF therapy, there was a significant increase/deterioration in both PED area (2.68 mm2 to 5.18 mm2, P < 0.05) and PED volume (0.39 mm3 to 1.07 mm3, P < 0.05); however, both parameters improved after switching to brolucizumab (3.81 mm2 and 0.37 mm3, P < 0.05). Our results suggest a favourable anatomical and visual response after treatment switch to brolucizumab in patients with nAMD refractory to previous anti-VEGF agents.

Cavitary Choroidal Nevus Showing Thickness Fluctuations in Response to Anti-VEGF Therapy for Diabetic Macular Edema: A Case Report.

To report the multimodal imaging features of a cavitary choroidal nevus showing thickness fluctuations that mirrored the response of diabetic macular edema (DME) to intravitreal anti-vascular endothelial growth factor (VEGF) therapy. Retrospective case report. Multimodal imaging findings including fundus photography, optical coherence tomography (OCT), fluorescein (FA) and indocyanine green angiography (ICGA), OCT-angiography (OCTA), and B-scan ultrasonography were analyzed. A female in her 80s with a cavitary choroidal nevus and DME was treated with intravitreal anti-VEGF therapy using a pro re nata regimen over 5 years. The choroidal nevus showed thickness fluctuations paralleling the response of DME to anti-VEGF therapy. Worsening of the DME was associated with marked increased choroidal lesion thickness on OCT. Conversely, resolution of DME after intravitreal anti-VEGF injections was followed by choroidal lesion flattening on OCT. Variations of the choroidal lesion thickness were mainly dependent on changes of intralesional hyporeflective caverns on OCT. Our report shows thickness variations of a cavitary choroidal nevus that paralleled the clinical course of DME treated with intravitreal anti-VEGF therapy. To the best of our knowledge, this is the first report on volume variations of a cavitary choroidal nevus following anti-VEGF therapy.

Exploring the Relationship between Anti-VEGF Therapy and Glaucoma: Implications for Management Strategies.

A short-term increase in intraocular pressure (IOP) is a common side effect after intravitreal anti-VEGF therapy, but a sustained increase in IOP with the development of secondary glaucoma has also been reported in some studies after repeated intravitreal anti-VEGF injections. The aim of this review is to present and discuss the possible pathophysiological mechanisms and factors contributing to a sustained rise in IOP, as well as treatment strategies for patients at risk. Close monitoring and adjustable IOP-lowering treatment are recommended for high-risk patients, including those with glaucoma, angle-closure anomalies, ocular hypertension or family history of glaucoma; patients receiving a high number of injections or at shorter intervals; and patients with capsulotomy. Strategies are needed to identify patients at risk in a timely manner and to prevent sustained elevation of IOP.