Intravitreal anti-VEGF Agents Research Articles

A meta-analysis of intravitreal ranibizumab versus laser photocoagulation for the treatment of retinopathy of prematurity.

Laser photocoagulation (LPC) has been a traditional treatment for retinopathy of prematurity (ROP). However, intravitreal anti-VEGF agents such as bevacizumab and ranibizumab (IVR) have also been increasingly used. This meta-analysis aims to rigorously compare IVR to LPC in the treatment of ROP. Medline, Embase and Cochrane CENTRAL were used to identify studies comparing IVR monotherapy to LPC (PROSPERO ID: CRD42023390855). The primary outcome was ROP regression. Secondary outcomes included likelihood of additional treatment, time from treatment to reactivation or re-treatment, refractive outcomes and adverse events such as retinal detachment, cataract, macular dragging/ectopia, vitreous or retinal hemorrhage, glaucoma, and endophthalmitis. A random effects meta-analysis was designed. 2361 articles were identified. 1947 eyes from 7 cohort studies, 1 case-control study and 2 RCTs were included with a median follow-up of 21 months (range: 11-75 months). There was no significant difference in disease regression between IVR and LPC (risk ratio [RR]=0.96, 95% confidence interval [CI] [0.83, 1.10], p=0.52), however, eyes that underwent IVR were associated with a higher likelihood of requiring additional treatment (RR= 2.70, CI= [1.55, 4.68], p<0.001). Although less frequent, retreatment occurred earlier with LPC compared to IVR (weighted mean difference (WMD)= -4.29 weeks, CI= [-6.48, -2.10], p<0.001). Furthermore, eyes that received IVR had a lower refractive error, with a WMD of -0.93 diopters (CI= [-1.54, -0.32], p=0.003) at a median age of assessment of 5.0 years (range 1.5-6.3 years). There was no difference in the rate of adverse events between LPC and IVR (p>0.05 for RD, MDR, VH and cataract). Quality of evidence was rated moderate for likelihood and time of additional treatment, as well as refractive error, but was considered low for disease regression and adverse events. Compared to LPC, IVR was associated with a higher likelihood of requiring additional treatment but a lower risk of myopia. More studies are needed to evaluate dose-response relationships and temporal trends in ROP regression following these treatments.

Comparison of Renal Adverse Events Between Intravitreal Anti-Vascular Endothelial Growth Factor Agents: A Meta-Analysis.

To compare the risk of renal adverse events, particularly acute kidney injury (AKI), between intravitreal anti-vascular endothelial growth factor (anti-VEGF) agents. Meta-analysis. A systematic literature search was conducted on Ovid Medline, Embase, and the Cochrane Library for randomized controlled trials (RCTs) published from January 2005 to February 2024 involving adult patients receiving anti-VEGF intravitreal injections for age-related macular degeneration, diabetic macular edema, and macular edema secondary to retinal vein occlusion. The primary outcome was the comparative risk of AKI between anti-VEGF agents and sham injections. Secondary outcomes involved other renal adverse events. Subgroup analyses were conducted by specific disease indications. A random-effects model was used for meta-analysis to estimate risk ratios (RRs) and their 95% confidence intervals, with a P value of <.05 representing statistical significance. Risk of bias was assessed using the Cochrane Risk of Bias 2 (ROB2) tool, and the certainty of evidence was evaluated through the Cochrane Grading of Recommendations, Assessment, Development and Evaluation (GRADE) framework. A total of 10,031 eyes from 11 RCTs were included. No significant differences were found in the risk of acute or chronic renal conditions, obstructive uropathies, neoplasia, or infectious processes between anti-VEGF agents and sham therapy. AKI was reported in 5.4% (n = 10/185) of patients treated with bevacizumab, 1.3% (n = 6/456) with sham, 1.0% (n = 48/4724) with aflibercept, 0.8% (n = 15/1929) with faricimab, 0.5% (n = 5/1098) with brolucizumab, and 0.3% (n = 5/1639) with ranibizumab. No significant differences in AKI risk were observed between any of the anti-VEGF agents and sham (P > .05 for all comparisons). However, there was an increased risk of patient-reported symptoms with 1.25 mg bevacizumab compared to 2 mg aflibercept (RR = 3.26, 95% CI = 1.07-9.93, P = .04), driven primarily by reports of hematuria: 4.3% (bevacizumab), 0.7% (sham), 0.2% (aflibercept), 0.1% (faricimab), and 0.1% (ranibizumab). US Food and Drug Administration (FDA)-approved intravitreal anti-VEGF agents do not significantly increase the risk of AKI compared to sham injections. Nevertheless, variations in patient-reported renal symptoms were observed across different anti-VEGF drugs. These variations were influenced primarily by differences in hematuria events, which may be a result of differential systemic absorption by these agents. These results underscore the importance of continuous monitoring and pharmacovigilance.

Proton beam irradiation with anti-VEGF therapy for polypoidal choroidal vasculopathy: results of a 24-month, phase II randomized study.

To determine the efficacy and safety of proton beam irradiation (PBI) and anti-vascular endothelial growth factor (anti-VEGF) therapy for polypoidal choroidal vasculopathy (PCV)/ aneurysmal type 1 macular neovascularization (AT1). The randomized clinical trial consisted of newly diagnosed active PCV/AT1 patients who were randomized 1:1 to treatment with three initial monthly intravitreal anti-VEGF agent (conbercept) injections with or without single 14 GyE radiation. Subsequent anti-VEGF therapy was given pro re nata. The primary outcome measures were number of anti-VEGF injections, best-corrected visual acuity (BCVA), and central retinal thickness (CRT) at 24months. Secondary outcome measures included the polypoidal lesion regression rate, changes in the areas of polypoidal lesions and branching vascular network (BVN), and radiotherapy-related adverse events at 24months. A total of 45 eyes (86.5%) completed the 24-month follow-up. At 24months, the combination therapy group required fewer anti-VEGF injections compared with the monotherapy group (5.9 ± 4.1 vs. 8.8 ± 5.3; P = 0.04). The mean gains in BCVA and the mean decrease in CRT were not significantly different between the two groups (P = 0.85 and P = 0.17, respectively). Combination therapy was superior to monotherapy for complete polypoidal lesion regression (80.0% vs. 48%, P = 0.03) and change in BVN area (- 1.03 ± 1.24 mm2 vs. 0.36 ± 0.77 mm2, P < 0.01). The radiation-related microvascular abnormalities were observed in 55.0% of eyes following combination therapy at 15.7 ± 2.5months. PBI (14 GyE) combined with anti-VEGF therapy could decrease the need for additional anti-VEGF injections for PCV/AT1. Longer follow-up is needed to fully evaluate the long-term safety of PBI. What is known The current main methods for treating PCV/AT1 include anti-VEGF drugs as monotherapy or in combination with photodynamic therapy. However, some cases can be challenging with multiple repeated injections due to the relatively low regression rate of polyps and high recurrence rate. What is new Proton beam irradiation therapy with anti-VEGF drugs can synergistically promote the regression of polyps and the shrinkage of branching vascular network, and reduce the anti-VEGF treatment burden for patients with PCV/AT1. Radiation retinopathy was mild and did not appear to be visually significant at the 24-month follow-up. Proton beam irradiation can be a new strategy for the treatment of PCV/AT1.

Effect of Intravitreal Bevacizumab (Anti VEGF) Injection on Renal Function

Background: Vascular endothelial growth factor (VEGF) plays an important role in the development of both Proliferative Diabetic Retinopathy (PDR) &amp; Diabetic Macular Odema (DMO). An intravitreal anti-VEGF agent is an effective new modality of treatment. Some studies have dealt with systemic effects of intravitreal injection of anti-VEGF. However, decreasing renal function has been reported recently. Aims: To investigate the effect of intravitreal bevacizumab (anti VEGF) injection on renal function. Methods: This quasi-experimental study was carried out in the Department of ophthalmology, Bangabandhu Sheikh Mujib Medical University, Dhaka, during March 2019 to August 2021. A total of 40 patients with retinopathy treated with intravitreal injection bevacizumab were included in this study, out of which 20 patients having diabetic kidney disease (DKD) and rest 20 patients without diabetic kidney disease (No DKD). The patients having Diabetic Kidney Disease (DKD) whose Urinary Albumin Creatinine Ratio (UACR) &gt; 30 mg/g or Effective Glomerular Filtration Rate (eGFR) &lt; 60mL/min/1.73m2, No Diabetic Kidney Disease (No DKD) whose UACR &lt; 30 mg/g or eGFR &gt; 60mL/min/1.73m2. Patients of both sexes and age above 18 years were enrolled in this study. Pre- injection and 1 month after 3rd dose of intravitreal injection of bevacizumab, UACR, Serum Creatinine and eGFR were measured and compared. Results: It was observed that half (50.0%) of the patients in DKD and more than half (65.0%) in No DKD belonged to age group 50-59 years. Male was predominant in both the groups. The mean pre-injection of serum creatinine was 1.23±0.53 mg/dl in DKD and 0.87±0.22 mg/dl in No DKD. The mean post-injection of serum creatinine was 1.19±0.45 mg/dl in DKD and 0.87±0.16 mg/dl in No DKD. The mean pre-injection of UACR was 1294.9±968.26 mg/g in DKD and 13.8±5.99 mg/g in No DKD. The mean post-injection of UACR was 1142.11±1024.06 mg/g in DKD and 13.01±6.87 mg/g in No DKD. The mean difference of serum creatinine, eGFR and UACR were not significant (p&gt;0.05) between pre-injection and post-injection in both groups. Conclusion: Serum creatinine, eGFR and UACR were almost similar between pre-injection and post-injection in patients with diabetic kidney disease (DKD) and patients without diabetic kidney disease (No DKD).

Bilateral Anti-VEGF on Same-Day-Investigation on Safety in Retinopathy of Prematurity: A Multicenter Retrospective Study

PurposeTo report incidence of procedure related complications in preterm infants with ROP treated with intravitreal anti vascular endothelial growth factors (anti VEGF) injection in both eyes on same day DesignRetrospective, multicenter case series SubjectsPreterm infants with ROP treated with anti VEGF bilaterally on same day MethodsIntervention: All included infants underwent intravitreal anti VEGF injection in both eyes under aseptic precautions in ophthalmic operation theatre (OT) or neonatal intensive care unit (NICU). Postoperative examination was performed to look for procedure related complications Main Outcome MeasuresIncidence of procedure related complication (Presumed endophthalmitis, intraocular inflammation, lens injury, vitreous hemorrhage, retinal tear) in the study cohort. To study association of indication, type of anti VEGF, type of needle used, setting of procedure, site of injection (distance from limbus) and experience of the treating ophthalmologist with the complications. Results9984 eyes of 4992 infants were analysed. The procedure was most commonly performed in ophthalmic OT (8258, 82.7%) using 29G (4514, 45.2%) needle between 1-1.5 mm (9984, 100%) from limbus. Aggressive retinopathy of prematurity was the most common indication for anti VEGF use (4866, 48.7%) while Bevacizumab was the most commonly used anti VEGF agent (8642, 86.6%). Overall, 26 eyes (0.3%) had procedure related complications. Lens injury (15, 0.15%) and presumed endophthalmitis (7, 0.07%) were most common complications. One eye had culture proven endophthalmitis with Pseudomonas aeruginosa. No case of bilateral endophthalmitis was noted. Endophthalmitis was not associated with setting of procedure or type of anti VEGF used, while risk of lens injury was seven times higher when performed in NICU and 30 times higher when performed by an ophthalmologist with < 1year of experience in injecting anti VEGF in preterm infants. ConclusionsThe incidence of presumed endophthalmitis after bilateral same day anti VEGF in infants with ROP is 0.07%. These infants can be treated in both eyes on same day with the anti VEGFs and needles (29-32G) evaluated in this study, with emphasis on the direction of needle parallel to visual axis. Extra precaution is advocated if the procedure is planned in NICU or by an ophthalmologist with limited experience.

OCT Angiography Biomarkers in Diabetic Macular Edema Patients Treated with Intravitreal Injection of Anti-VEGF

Abstract Purpose To correlate quantitative OCT angiography (OCTA) biomarkers with clinical features and to predict the responce after ranibizumab treatment for diabetic macular edema (DME) with OCTA biomarkers. Design Non randomized non controlled observational study on 20 eyes with DME set in the Ophthalmology Department, Ain Shams University. Study subjects were selected randomly from patients attending the ophthalmology outpatient clinics during the recruitment period, which took place between December 2020 and December 2022. Participants The study was conducted on twenty eyes from 20 patients of with diabetic macular edema, with the exception of media opacity and high refractive error, from Ain Shams University hospital. Methods All patients underwent Spectral Domain Optical Coherence Tomography (SD-OCT) (RTVue XR OCT Avanti; Optovue, Fremont, USA) with Macular scan including 6x6mm scans centered on the fovea at baseline evaluation and at 1 month, 3 months and 6 months while on treatment with intravitreal antiVEGF (Ranibizumab) injections following the PRN protocol without loading. Main Outcome Measures OCTA biomarkers, including foveal avascular zone (FAZ) area (FAZ-A), FAZ acircularity index (FAZ-AI), FAZ perimeter and vessel density (VD), were analyzed comprehensively. Best-corrected visual acuity (BCVA) and central retinal thickness (CRT) also were obtained. Results After the ranibizumab treatment, there was a statistically significant decrease in the FAZ area and FAZ perimeter during the follow up period denoting improved vascular perfusion, and the FAZ AI decreased significantly denoting that the FAZ regained its regularity. There was a statistically significant increase in the mean vessel density including the overall, parafoveal and perifoveal vessel density in the superficial and deep plexus during the follow up period, this might be explained by decreased artifacts due to macular edema. There was a statistically significant difference in the parafoveal vessel density in the SCP, FAZ area, FAZ perimeter, and AI at baseline between good and poor responders. These biomarkers could be used as predictors for response after treatment with anti VEGF in eyes with DME. Conclusions For eyes with DME, parafoveal VD in the superficial layer, FAZ area and perimeter at baseline were independent predictors for visual improvement after the ranibizumab treatment.

Review of Guideline Recommendations for Optimal Anti-VEGF Therapy in Age-Related Macular Degeneration.

Neovascular age-related macular degeneration is a progressive, blinding macular disease that has become a burden both in healthcare systems and the global economy. The vascular endothelial growth factor (VEGF) is the main agent involved in the pathogenic process of the disease. The main goal of the age-related macular degeneration treatment is to maintain and improve visual acuity by injecting intravitreal anti-VEGF agents in either a reactive or proactive manner. Subretinal and intraretinal fluids are the main biomarkers that should be considered when managing the frequency of the therapy. This review discusses both functional and morphological treatment criteria according to current recommendations as opposed to real-life situations encountered during day-to-day clinical practice and highlights situations in which the benefits of continuing therapy are arguable in terms of improving patients' quality of life. Optimizing the treatment regimen represents an important aim of current clinical ophthalmological practice, as age-related macular degeneration patients usually have a long follow-up period.

Complement Inhibitors for Geographic Atrophy in Age-Related Macular Degeneration-A Systematic Review.

Age-related macular degeneration (AMD) is one of the main causes of blindness and visual impairment worldwide. Intravitreal complement inhibitors are an emergent approach in the treatment of AMD, which have had encouraging results. This systematic review analyzes the outcomes and safety of complement inhibitor therapies for GA in AMD cases. A comprehensive search on the PubMed and Web of Science databases returned 18 studies involving various complement inhibitor agents, with a total of 4272 patients and a mean follow-up of 68.2 ± 20.4 weeks. Most treated patients were white (96.8%) and female (55.8%), with a mean age of 78.3 ± 7.8 years and a mean GA area of 8.0 ± 3.9 mm2. There were no differences in visual function change between treated and control participants. The mean GA area change was 2.4 ± 0.7 mm2 in treated participants vs. 2.7 ± 0.8 mm2 in control groups (p < 0.001). The ocular and systemic side effects were similar to those of intravitreal anti-VEGF. A less-understood effect was that of the onset of choroidal neovascularization (CNV) in 1.1-13% of patients; this effect was found to be more frequent in patients with neovascular AMD in the fellow eye or nonexudative CNV in the study eye at baseline. Complement inhibitors may represent a useful therapy for GA in AMD, but a personalized approach to patient selection is necessary to optimize the outcomes.

Evaluation of Foveal Vasculature by Optical Coherence Tomography Angiography after Pan-Retinal Photocoagulation versus Intravitreal Anti-VEGF Injections.

This study aimed to compare macular vascular changes one and three months after treatment with either panretinal photocoagulation (PRP) or intravitreal bevacizumab (IVB). A total of 62 eyes with very severe non-proliferative diabetic retinopathy or early proliferative diabetic retinopathy without center-involved diabetic macular edema, were included in this retrospective study. Thirty-nine eyes were allocated to the PRP group, while 23 eyes were treated with IVB. Optical coherence tomography angiography (OCTA) was performed to measure foveal avascular zone (FAZ) characteristics as well as the densities of superficial and deep capillary plexuses (SCP and DCP). In the IVB group, the FAZ area and perimeter expanded at month one but returned to baseline level after three months. In the PRP group, however, the FAZ area and perimeter were rather steady. Changes in the FAZ area were significantly different between the treatment groups at month one (P = 0.02), but not at month three (P = 0.31). There was no significant difference in the change in FAZ circularity index between the two groups at each time point (P = 0.55 and P = 0.31). Similarly, changes in SCP density were not statistically significant between the two groups at both time points (all Ps 0.05). A comparison of the two treatment arms based on the mean change in DCP density revealed a significant difference at month one, but not at month three (P = 0.01 and P = 0.49, respectively). Although bevacizumab and PRP have different short-term macular vascular responses, both therapies have the ability to normalize or stabilize vascular measures over time.

Sea-fan retinal neovascularization associated with rickettsial retinitis: a case report

BackgroundRickettsial disease has been commonly associated with retinitis, retinal vasculitis, and optic nerve involvement, but the development of retinal neovascularization has been very rarely reported. We herein describe a case of rickettsial retinitis complicated with the development of sea-fan retinal neovascularization documented with multimodal imaging, including fundus photography, SS-OCT, fluorescein angiography, and SS-OCT angiography.Case presentationA 26-year-old female with a history of fever one week earlier presented with sudden decreased vision in the left eye. Best-corrected visual acuity (BCVA) was 20/2000 and the patient was diagnosed with rickettsial retinitis along the superotemporal retinal vascular arcade associated with serous retinal detachment and retinal hard exudates. The indirect immunofluorescence test was positive for Rickettsia conorii, and the patient was treated with oral doxycycline (200 mg/day) and oral prednisone (0.75 mg/kg/day, with gradual tapering). Four weeks after presentation, the retinal infiltrate and associated serous retinal detachment had resolved, but retinal hard exudates had increased. A large sea-fan preretinal fibrovascular neovascularization became apparent along the superotemporal retinal vascular arcade, but there was no associated retinal ischemia on fluorescein angiography. The patient received an adjunctive single intravitreal injection of 1.25 bevacizumab. Sequential follow-up examinations showed shrinking of sea-fan retinal neovascularization, a complete resolution of retinal hard exudates, and the development of a self-limited vitreous hemorrhage. On last follow-up, 30 months after intravitreal bevacizumab injection, BCVA was 20/25.ConclusionPatients with rickettsial retinitis may develop a sea-fan retinal neovascularization, with subsequent vitreous hemorrhage, putatively through inflammatory mechanisms. Multimodal imaging including OCT, fluorescein angiography, and OCT-angiography, is highly useful for accurate diagnosis and reliable monitoring of the evolution of retinitis, retinal neovascularization, and other retinal changes. The use of a combination therapy with oral doxycycline and corticosteroids and intravitreal anti-VEGF can improve outcomes.

Investigation of the effect of intravitreal bevacizumab treatment on left heart function using speckle tracking echocardiography

Introduction and objectivesVascular endothelial growth factor (VEGF) inhibitors are widely used in oncology and ophthalmology. Although these agents have been shown to increase the risk of cardiovascular events in systemic use, the effect of local applications is unclear. In our study, we aimed to investigate the effects of anti-VEGF agents on left heart functions after intravitreal injection using speckle tracking echocardiography. MethodsIn this prospectively designed study, 44 patients who were going to start intravitreal anti-VEGF treatment were included in the study. Patients were evaluated with speckle tracking echocardiography before the first anti-VEGF administration and at three months of anti-VEGF treatment. ResultsGlobal longitudinal strain (GLS) values at three months were lower in the patients who participated in the study and this was statistically significant (−18.77±2.17, −18.60±2.01, p=0.001). Also, there was a statistically significant decrease in the mean values of GLS (GLS4CH) obtained from apical four space image, GLS (GLSAPLAX) obtained from apical long axis image and GLS (GLS2CH) obtained from apical 2 space image at month 0 and month 3 (−19.08±2.39, −18.93±2.26, p=0.004; −18.81±2.29, −18.60±2.12, p=0.001; −18.44±2.31, −18.27±2.12, p=0.013, respectively). ConclusionThe slight decrease in GLS in our study suggests that the use of intravitreal anti-VEGF agents may have cardiac effects.

Efficacy of Indirect Laser Photocoagulation in Cases with Retinopathy of Prematurity Presenting with Late Stage 3 Turning into Stage 4A

Abstract Background Retinopathy of prematurity (ROP) is a preventable irreversible cause of blindness in children especially in developing countries. Early detection and management of type 1 ROP with intravitreal injection of Anti-VEGF or indirect laser photocoagulation is the cornerstone of preventing blindness from this disease. Screening programs for ROP are mandatory for picking cases early before retinal detachment develops. Standardized screening programs are still lacking in developing countries, like Egypt, so cases may present in later stages. Cases presenting too late with Stage 4 and 5 ROP are managed surgically with lens-sparing vitrectomy or lensectomy vitrectomy. A portion of the cases present at the transition from stage 3 into stage 4a ROP. Management of those cases with intravitreal anti-VEGF was reported to cause acute crunch and tractional retinal detachment. Management with laser photocoagulation has not been discussed before. Methods This is a retrospective interventional, non-comparative study. Review of records of ROP cases presenting after 4 weeks from delivery having stage 3 turning into stage 4a ROP for which indirect laser photocoagulation was done were collected in the period from January 2017 till May 2019. Gestational age, birth weight, postmenstrual age at first presentation, date of laser photocoagulation and number of sessions, fundus images showing initial regression and final regression and if any recurrences happened were recorded. Results Nine treatment naive eyes of five premature infants were included. Mean GA was 30.4+/- 1.5 wks (range, 28-32 wks; median, 31). Mean BW 1190+/- 174.6 gm (range, 900-1300; median = 1300). Mean PMA at presentation 42.5+/-5.7 wks (range, 38.5-52.5; median, 40.5). All 9 eyes presented with plus disease and highly elevated fibrovascular ridge with significant fibrous component in Zone II. 7 eyes (77.7%) had secondary retinoschisis, localized tractional retinal detachment. 2 eyes (22.2%) showed temporal dragging. All eyes received Indirect laser photocoagulation to the avascular retina (near confluent burns) one session for each eye. No skip areas were reported. 5 eyes (3 patients) were done under topical anesthesia and 4 (2 patients) under general anesthesia. All 9 eyes (100%) showed complete regression of ROP with release of traction, restoration of retinal anatomy at a mean of 3.7+/- 2.7 months (range, 2-8.5 months; median, 2.5 months). Conclusion Indirect laser photocoagulation is an effective treatment measure in premature infants presenting late with fibrovascular proliferation having high fibrous components and starting Stage 4a ROP in Zone II. Laser rather than IVI of Anti-VEGF may save those infants from crunch phenomenon and need for vitrectomy with final good anatomical and thus visual outcomes.

Role of inflammation in a rat model of radiation retinopathy

Radiation retinopathy (RR) is a major side effect of ocular tumor treatment by plaque brachytherapy or proton beam therapy. RR manifests as delayed and progressive microvasculopathy, ischemia and macular edema, ultimately leading to vision loss, neovascular glaucoma, and, in extreme cases, secondary enucleation. Intravitreal anti-VEGF agents, steroids and laser photocoagulation have limited effects on RR. The role of retinal inflammation and its contribution to the microvascular damage occurring in RR remain incompletely understood. To explore cellular and vascular events after irradiation, we analyzed their time course at 1 week, 1 month and 6 months after rat eyes received 45 Gy X-beam photons. Müller glial cells, astrocytes and microglia were rapidly activated, and these markers of retinal inflammation persisted for 6 months after irradiation. This was accompanied by early cell death in the outer retina, which persisted at later time points, leading to retinal thinning. A delayed loss of small retinal capillaries and retinal hypoxia were observed after 6 months, indicating inner blood‒retinal barrier (BRB) alteration but without cell death in the inner retina. Moreover, activated microglial cells invaded the entire retina and surrounded retinal vessels, suggesting the role of inflammation in vascular alteration and in retinal cell death. Radiation also triggered early and persistent invasion of the retinal pigment epithelium by microglia and macrophages, contributing to outer BRB disruption. This study highlights the role of progressive and long-lasting inflammatory mechanisms in RR development and demonstrates the relevance of this rat model to investigate human pathology.

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.

Does addition of intravitreal bevacizumab confer additional benefit in management of proliferative diabetic retinopathy?

To evaluate visual outcome and complications of PDR after treatment with Intravitreal Bevacizumab followed by Pan Retinal Photocoagulation A hospital based retrospective study was done in the Department of Ophthalmology, to evaluate visual outcome and complications of PDR after treatment with intravitreal Bevacizumab followed by Pan Retinal Photocoagulation. Visual Acuity, Dilated fundus examination, OCT macula were done on subsequent follow ups 135 eyes of 133 patients were included in the study.The mean pre procedure visual acuity is 0.639±0.5327 which improved to 0.451±0.4089 post procedure. P value is &amp;#60;0.001 which is statistically significant.i.e, 94 (69.62%) eyes had improved vision, 21(15.55%) had stable vision and 20(14.81%) eyes had decreased vision. After injection followed by PRP out of 135 eyes,4(2.96%) eyes developed vitreous hemorrhage which resolved with repeat intravitreal anti-VEGF injection, 6(4.44%) eyes developed diabetic macular edema,3(2.2%) eyes developed Neovascularisation of iris and 4(2.96%)eyes developed vitreous hemorrhage with traction retinal detachment.From our study it appears that addition of intravitreal anti VEGF to Pan Retinal Photocoagulation for PDR confers the additional benefit of less incidence of vitreous hemorrhage and less incidence of traction retinal detachment requiring surgery in the 1 one year of follow up. This amounts to more compliance by the patient for taking the treatment as well as better visual outcome

Similar Risk of Kidney Failure among Patients with Blinding Diseases Who Receive Ranibizumab, Aflibercept, and Bevacizumab: An Observational Health Data Sciences and Informatics Network Study

Objective or PurposeA) To characterize the incidence of kidney failure associated with intravitreal anti-vascular endothelial growth factor (VEGF) exposure, and B) compare the risk of kidney failure in patients treated with ranibizumab, aflibercept, or bevacizumab. DesignRetrospective cohort study across 12 databases in the Observational Health Data Sciences and Informatics (OHDSI) network. Subjects, Participants, and/or ControlsSubjects aged ≥18 years with ≥3 monthly intravitreal anti-VEGF medications for a blinding disease (diabetic retinopathy, diabetic macular edema, exudative age-related macular degeneration, or retinal vein occlusion). Methods, Intervention, or TestingA) The standardized incidence proportions and rates of kidney failure while on treatment with anti-VEGF were calculated. B) For each comparison (e.g., aflibercept versus ranibizumab), patients from each group were matched 1:1 using propensity scores. Cox proportional hazards models were used to estimate the risk of kidney failure while on treatment. A random-effects meta-analysis was performed to combine each database’s hazard ratio (HR) estimate into a single network-wide estimate. Main Outcome MeasuresIncidence of kidney failure while on anti-VEGF treatment, and time from cohort entry to kidney failure. ResultsOf the 6.1 million patients with blinding diseases, 37,189 who received ranibizumab, 39,447 aflibercept, and 163,611 bevacizumab were included; the total treatment exposure time was 161,724 person-years. The average standardized incidence proportion of kidney failure was 678 per 100,000 persons (range 0 to 2389), and incidence rate 743 per 100,000 person-years (0 to 2661). The meta-analysis HR of kidney failure comparing aflibercept to ranibizumab was 1.01 (95% confidence interval (CI) 0.70, 1.47, p=0.45), ranibizumab to bevacizumab 0.95 (95% CI 0.68, 1.32, p=0.62), and aflibercept to bevacizumab 0.95 (95% CI 0.65, 1.39, p=0.60). ConclusionsThere was no substantially different relative risk for kidney failure between those who received ranibizumab, bevacizumab, or aflibercept. Practicing ophthalmologists and nephrologists should be aware of the risk for kidney failure among patients receiving intravitreal anti-VEGF medications and that there is little empirical evidence to preferentially choose among the specific intravitreal anti-VEGF agents.

Subthreshold laser treatment for non-center involved diabetic macular edema via non-damaging retinal laser therapy (NRT).

To evaluate the efficacy of subthreshold laser treatment via non-damaging retinal laser therapy (NRT) in patients with non-center involved diabetic macular edema (non-CI DME). In this prospective controlled study, NRT with 577nm wavelength was performed to the edematous inner subfields as needed at 3 monthly intervals, while the control group received no treatment. If CI-DME developed in either group, intravitreal anti-VEGF was performed and the eye was excluded from subsequent analysis. A total of 75 eyes (36 study eyes, 39 controls) were evaluated. The change in superior, nasal and temporal inner subfield thicknesses over time and between groups was found significant (P = 0.004, P < 0.001, P = 0.04 respectively). Best corrected visual acuity (BCVA) change was not significant over time and between groups (P = 0.69). Rates of CI-DME development requiring intravitreal anti-VEGF treatment were not different during the first and second years (P = 0.171, 0.908). No laser scar was detected in any eye in fundus autofluorescence imaging. NRT performed as needed at 3 monthly intervals is effective after 21months of follow up in the treatment of non-CI DME and it was safe. With this method, it may be foreseen that BCVA will be better preserved in the long term by avoiding the possible side effects of conventional laser.

Multiple Choroidal Neovascularizations in Choroidal Osteoma Treated with Anti-VEGF Injections: A 6-Year Follow-Up Case Report.

To report a case of multiple choroidal neovascularizations (CNVs) secondary to choroidal osteoma injected with a total of 13 anti-vascular endothelial growth factor (VEGF) drugs over a long-term follow up of 6-year period. Case report. A 29-year-old female presented with a peripapillary choroidal osteoma in her left eye with the best-corrected visual acuity (BCVA) of 20/25. After 2 years of follow-up, two foci of CNV (one was at the infra-nasal of the optic disc, and the other was near the sub-temporal vascular arch), and massive subretinal hemorrhage developed overlying the osteoma, causing decreased BCVA of 20/33. The patient was treated with four consecutive intravitreal injections of conbercept and the two CNVs regressed with BCVA recovered to 20/25. While 17 months later, the third CNV lesion locating at the fovea appeared and nine more injections of aflibercept were given during which repeated recurrence of it occurred. At last follow-up, 6 years from baseline, all the three CNV foci were controlled, with final BCVA of 20/33. Multiple CNVs may appear simultaneously at different locations in one osteoma and prompt treatment with intravitreal anti-VEGF may be a good option to control the progression and recurrence of these CNVs. Long-term follow-up and multimodal imaging are vital in the management of CO-associated CNV.

Clinical Landscape of Central Serous Chorioretinopathy in Germany: Retina.net CSC Registry Report Number 1

Introduction: The German Registry of central serous chorioretinopathy (CSC) collects data on CSC patients in a nationwide multicenter approach to analyze epidemiology, risk factors, clinical presentations, as well as diagnosis and treatment patterns. Methods: In this multicenter cohort study, patients with CSC were enrolled in nine tertiary referral centers in Germany between January 2022 and June 2023. After consenting to the study, demographic data, risk factors, reported symptoms, best-corrected visual acuity (BCVA), funduscopic findings, disease severity, and diagnostic and treatment decisions were recorded and analyzed. Results: A total of 539 eyes of 411 CSC patients were enrolled in this study including 308 males (75%) and 103 females (25%). Patients were predominantly of Caucasian origin and had a mean age of 55.5 years (IQR 41.0–70.0). 28% of eyes were classified as acute (<4 months duration) CSC, 28% as chronic (>4 months duration) CSC, 21% as inactive CSC, 11% as chronic atrophic CSC, and 12% as CSC with secondary CNV. 128 patients (31%) demonstrated bilateral CSC. The most common risk factors reported were psychological stress (52%), smoking (38%), arterial hypertension (38%), and a history of or current use of steroids (30%). Most frequently encountered symptoms included decreased visual acuity (76%), metamorphopsia (49%), relative scotoma (47%), blurred vision (19%), and dyschromatopsia (9%). The mean logMAR BCVA on initial examination was 0.2 (≈20/30, IQR 0.2–0.4) but showed significant variation with a tendency of lower BCVA in chronic cases. At the baseline visit, 74% of the overall cohort received no treatment, while 19% underwent local treatment and only 2% underwent systemic treatment. Of the local therapies, anti-VEGF injections were the most frequently performed procedure (33%, mainly for secondary CNV), followed by micropulse laser (28%), focal nonpulsed laser (23%), verteporfin photodynamic therapy (14%), and nonsteroidal anti-inflammatory eye drops (2%). Among intravitreal anti-VEGF agents, aflibercept was used most frequently, followed by bevacizumab and ranibizumab. Conclusion: This registry represents one of the largest cohorts of European patients with CSC to date. Patient age and the proportion of women were higher than expected and bilateral active disease was lower than anticipated, highlighting that neither age nor gender should be overemphasized when diagnosing CSC. Therapeutic interventions are heterogeneous and include verteporfin photodynamic therapy, micropulse laser, and anti-VEGF injections in case of secondary CNV.

A Case Report Intravitreal Anti VEGF Bevacizumab on Patient with Hypertension Retinopathy and Exudative Retinal Detachment

Introduction : To present a case of intravitreal anti VEGF bevacizumab function on patient with hypertension retinopathy and exudative retinal detachment.&#x0D; Case Illustration : A 29 years old man presented with chief complaint blurry vision with visual acuity 1/60 on both eyes. History of hypertension sinced one year ago and already got hemodialisa treatment twice a week sinced 6 months ago. Ophthalmic examination showed decreased vision on both eyes and posterior segment both eyes we can find macular star and papil edema. Patient had diagnosed with hypertension retinopathy scheie 4 and exudative retinal detachment both eyes.&#x0D; Discussion : Hypertension will cause blood vessels to become damage in the form of sclerosis, thickening of blood vessel walls, and plasma leakage. Hypertension retinopathy acts as predictor of systemic morbidity and mortality due to organ target damage. Regulating systemic disease like blood pressure to become normal will improve clinical signs of hypertension retinopathy. Administration of anti-VEGF intravitreal injection therapy like bevacizumab can improve permeability of blood vessels in retina and decreased volume of exudate in retina. Visual acuity for this patient will improve to become 4/60 for both eyes.&#x0D; Conclusion : Uncontrolled hypertension can lead to organ target damage, which one of that was eyes. Hypertension retinopathy can make complications like exudative retinal detachment if the blood pressure still uncontrolled. Management of exudative retinal detachment caused by hypertension retinopathy was giving intravitreal anti VEGF injection in eyes to repair breakdown of blood retinal barrier, and the blood pressure must be well controlled to maintain permeability of blood retinal barrier.