Intravitreal Bevacizumab Research Articles

Biosimilars of anti‐vascular endothelial growth factors for ophthalmic disease – Clinical trial status 2022

AbstractPurpose: Diabetic Macular Œdema (DME) and Age‐related Macular Degeneration (nAMD) are the leading causes of vision loss in developed nations. Anti‐Vascular Endothelial Growth Factor (aVEGF) has revolutionized the treatment of both conditions, but access is limited by costs. Biosimilars of aVEGF can cut costs, but prescriber concerns over the lack of clinical data can slow uptake. This paper reports all biosimilar aVEGF in development for Europe and the USA, and pools the results of clinical confirmatory trials to provide statistically greater reassurance in the similarity of outcomes.Methods: Biosimilars in the clinical development phase were identified from US and EU trial registries.Results: There are 13 biosimilars of ranibizumab and aflibercept in final clinical comparative trial stage of development in Europe and the USA, recruiting 6126 patients. Five studies of intravitreal bevacizumab biosimilars are recruiting 772 patients. Equivalence outcomes are typically based on Best‐Corrected Visual Acuity (BCVA) with 90% confidence limits of −3 to +3 letters between reference and biosimilar medicines. Completed trials to date with 1166 participants analysed together show BCVA outcomes of ≤1 letter between Originator Reference Products and Biosimilars; for serious adverse events the risk ratio is 1.17, with 95% confidence intervals of 0.85–1.63, p = 0.32.Conclusions: Biosimilars of aVEGF are expected soon. There are likely sufficient brands expected to create meaningful price competition. To date, the EU/US regulatory pathway is delivering biosimilars with close equivalence of safety and efficacy outcomes.

Central serous chorioretinopathy complicated by neovascularization following panretinal photocoagulation for diabetic retinopathy

AbstractPurpose: To report a case of chronic central serous chorioretinopathy (CSCR) complicated by neovascularization following panretinal photocoagulation (PRP) for a proliferative diabetic retinopathy (DR).Methods: A 51‐year‐old man, with a medical history of diabetes mellitus and chronic CSCR presented to our department for alteration of central vision of the left eye (LE) 6 months after bilateral PRP for proliferative DR. Complete ophthalmic examination with best corrected visual acuity (BCVA) measurement, fundus photography, fundus autofluorescence (FAF), swept source optical coherence tomography (SS‐OCT), swept source optical coherence tomography angiography (SS‐OCTA) and indocyanine green angiography (ICG‐A) were performed.Results: BCVA was 20/100 in the right eye (RE) and 20/400 in the LE. Anterior segment examination was unremarkable except for a cataract in the RE. Fundoscopic examination of the LE showed multiple areas of retinal pigment epithelium (RPE) alteration and a temporal pigment epithelium detachment (PED). FAF showed multiple hypoautofluorescent lesions associated with gravitational tracks. SS‐OCT revealed a serous retinal detachment, a flat irregular PED with a double layer sign overlying a thickened choroid and dilated choroidal vessels. Mid‐phase ICGA revealed 2 discrete areas of hyperfluorescence. SS‐OCTA confirmed the presence of 2 well‐defined choroidal neovascular membranes. The patient was diagnosed with Pachychoroid Neovasculopathy (PNV). After 2 intravitreal bevacizumab injections, SS‐OCT showed complete resolution of the subretinal fluid whereas SS‐OCTA visualized a mature “dead‐tree” shaped membrane.Conclusions: This is an unusual case of chronic CSCR progressing to PNV following PRP for RD. The disruption of an active RPE pump mechanism or release of endogenous stress hormones after PRP have been suggested by some authors as possible causes of this progression. Further studies are needed to elucidate the exact pathogenesis.

Comparison Between Intra Vitreal Bevacizumab and Triamcinolone in Reducing Macular Thickness in Central Retinal Vein Occlusion

Objectives: To compare the effect of intra vitreal bevacizumab (IVB) and intra vitreal triamcinolone (IVT) in reducing macular thickness in central retinal vein occlusion. Methods and Materials: This quasi experimental study was conducted at Department of Ophthalmology, Hayat Abad Medical Complex Peshawar in the period from 01 January 2020 to 30 June 2020. Total 40 patients presented with central retinal vein occlusion (CRVO). Patients were divided into two groups, group A received IVB treatment and group B received IVT treatment. The patients were followed up on 6th month post treatment. The primary outcomes of the study were visual acuity and reduction in macular thickness on OCT post treatment. Results: 40 patients were enrolled in the study. The mean age of patients was 60.70±15.49 in group A and in group B 60.40±12.83. There were 13 males and 7 females in group A and 12 males and 8 females in group B. Mean VA at baseline was 1.0825±0.25 logMAR in group A and 0.9745±0.29 logMAR in group B. Mean macular thickness at baseline was 625.40±47.15 µm in group A and 642.05±44.23 µm in group B. Mean VA at 6th month post treatment follow up was 0.4195±0.23 logMAR in group A and in group B was 0.4960±0.27 logMAR. At 6th month follow up macular thickness was 261.80±26.269 µm in group A and 263.80±22.209 µm in group B. Conclusion: Intravitreal injections of bevacizumab and triamcinolone have shown a reduction in macular edema in CRVO patients along with improvement in visual acuity. Keywords: Bevacizumab, Triamcinolone, Macular Edema, Central Retinal Vein Occlusion, Visual Acuity

Postoperative Bleed after PARS Plana Vitrectomy with Pre-Operative Intra Vitreal Bevacizumab in Diabetic Patients with Advance Diabetic Eye Disease

Objectives: The aim of this study is to investigate the effect of preoperative intravitreal Bevacizumab on postoperative incidence of vitreous cavity hemorrhage in patients with advance diabetic eye disease undergoing 23 gauge pars plana vitrectomy. Study Duration: This study was conducted in the department of Ophthalmology Services Hospital Lahore from April 2021 to September 2021. Study Design: Randomized Controlled Trail Patients & Methods: Forty eyes of forty diabetic patients with advance diabetic eye disease were selected for three port 23 gauge pars plana vitrectomy (PPV) and were split into two groups of twenty patients each. One week before the pars plana vitrectomy, Group A received preoperative intravitreal bevacizumab (1.25 mg/0.05 ml) and sham injection were given to Group B patients and postoperative vitreous cavity bleeding was noted on day one , day three , day seven and bleeding was graded from no bleeding to mild and severe based on clinical examination. Practical implication: To assess the decrease in potential risk of postoperative vitreous cavity bleeding following 23 gauge three port pars plana vitrectomy Results: The patients in this study had an average age of 58.46 ±3.62 yrs and mean duration of diabetes among these patients selected for this trial was 11.25±1.52 years (range 8-22 years). Out of 20 eyes in Group A , 15 (75.0%) had no bleeding, 4 (20.0%) had mild and 1(5.0%) had severe postoperative vitreous cavity bleed. In group B , out of 20 eyes 11(55.0%) had no bleeding , 7(35%) had mild to moderate bleeding and 2(10.0%) had severe vitreous cavity hemorrhage. Conclusion: Preoperative Intravitreal bevacizumab prior to pars plana vitrectomy was found effective in reducing the risk of postoperative vitreous cavity bleeding in patients with advance diabetic eye disease. Keywords: Intravitreal Bevacizumab, advanced diabetic eye disease, vitreous hemorrhage, Postoperative bleed, Vitrectomy

Preliminary Study of Different Treatment Responses between Bevacizumab, Aflibercept and Dexamethasone Implant According to Renal Function in Diabetic Macular Edema Patients.

Background: The purpose of this study was to investigate the association between responses to intravitreal bevacizumab injection and renal function in diabetic macular edema (DME) patients. Methods: A retrospective study of the medical records of 104 treatment-naïve DME patients who received intravitreal bevacizumab injection (IVBI) was conducted. Based on the estimated glomerular filtration rate (eGFR, mL/min/1.73 m2), the participants were classified into three groups. Intergroup comparisons of the best-corrected visual acuity (BCVA) and central subfield retinal thickness (CST) changes were performed after three-monthly consecutive IVBIs. In the groups with decreased renal function, the response to further treatment with a different drug was investigated. Results: A total of 104 participants were included in the study: 60 participants in the preserved renal function group (eGFR ≥ 60), 25 participants in the moderate chronic kidney disease (CKD) group (30 ≤ eGFR < 60), and 19 participants in the severe CKD group (eGFR < 30). After three-monthly consecutive IVBIs, BCVA (p < 0.001) and CST (p < 0.001) were significantly improved only in the preserved renal function group. Following further treatment of patients with decreased renal function, the treatment results were significantly better in those who were switched to aflibercept or dexamethasone implant than in those who were maintained on IVBI. Conclusions: From this preliminary study, we observed that renal function might affect the response to IVBI treatment in patients with DME. In the case of a poor response to initial IVBI treatment for DME in patients with moderate to severe CKD, our study supports switching to the aflibercept or dexamethasone implant.

Polypoidal choroidal vasculopathy—characteristics and response to treatment with bevacizumab in caucasian patients

PurposeTo investigate the features and treatment response in Caucasian patients with polypoidal choroidal vasculopathy (PCV), initially treated with bevacizumab.Methods45 eyes of 43 treatment-naïve patients with PCV were included in this retrospective study, all uniformly initially treated with three bevacizumab injections monthly. OCT characteristics and clinical parameters were recorded and analyzed at presentation, after the initial 3 bevacizumab injections and at the final follow up period.ResultsFollowing 3 monthly bevacizumab injections visual acuity significantly improved with a mean gain of one line of vision. Central macular thickness (CMT) significantly improved from a mean of 402.1 ± 130.8 μm at presentation to 322.0 ± 96.8 μm (p < 0.01). Subretinal fluid, intraretinal fluid and submacular hemorrhage significantly improved. 53% were later switched to aflibercept and showed better response in the central macular thickness in comparison to those in which bevacizumab injections were continued. No correlation was found between the presence of pachyvessels or increased choroidal thickness and the improvement in VA or CMT.ConclusionFixed first-line treatment with intravitreal bevacizumab monotherapy in non-Asian PCV patients achieves satisfactory visual and anatomical outcomes.

Short-term outcomes in patients with center-involving diabetic macular edema after a single dose of intravitreal bevacizumab

BackgroundA significant portion of diabetic macular edema (DME) is refractory to anti-vascular endothelial growth factor (anti-VEGF) agents. This study investigates morphological and functional outcomes to a single intravitreal bevacizumab (IVB) injection in patients with center-involving DME (ciDME) at 4–6 weeks and compares treatment responders and non-responders based on spectral domain optical coherence tomography (SD-OCT) features.MethodsIRB approved observational, retrospective chart review of patients with ciDME, identified by ICD-10 code, who received IVB and underwent baseline and 4–6 weeks follow-up SD-OCT imaging between January 1, 2016 and January 19, 2021. Patients who had received previous treatment with anti-VEGF or intraocular steroids within 1 year were excluded. Variables included best-corrected visual acuity (BCVA), central subfield thickness (CST) and total macular volume (TMV). Eyes were classified as responders if CST reduction was greater than 10%. OCT scans were graded qualitatively by two masked graders using Imagivault software. Paired Student’s t-tests, Wilcoxon signed rank tests and Chi-Square tests were used for analysis.ResultsA total of 334 prospective subjects were identified, and after applying exclusion criteria 52 eyes from 46 patients (mean age 64.22 ± 8.12 years, 58.7% male) were included. Mean BCVA did not significantly change with treatment, 63.9 ETDRS letters (~ 20/50) at baseline and 65.9 ETDRS letters (~ 20/50) post-treatment (p = 0.07). Mean CST decreased from 466 ± 123 μm at baseline to 402 ± 86 μm post-treatment (p < 0.001). 22 (42.3%) of eyes were categorized as responders and 30 (57.7%) as non-responders. Average change in CST from baseline in responders was -164 μm (p < 0.001) and + 9 μm in non-responders (p = 0.47). Vitreomacular adhesion (VMA) was more prevalent in non-responders (28.7% vs. 4.8%, p = 0.03). In addition, cyst location in the inner nuclear layer (INL) was present more frequently in responders (95.5% vs. 73.3%, p = 0.037) as was subretinal fluid (45.5% vs. 13.3%, p = 0.01).ConclusionThe short-term response to a single IVB was sub-optimal with structural but no functional improvements. Greater baseline CST, presence of INL cysts and subretinal fluid may represent factors indicative of a better treatment response.

LONG-TERM TREATMENT OUTCOMES AFTER BEVACIZUMAB THERAPY FOR MACULAR NEOVASCULARIZATION IN WHITE PATIENTS WITH HIGH MYOPIA.

To report long-term treatment outcomes of intravitreal bevacizumab in myopic macular neovascularization (MNV). Retrospective analysis of longitudinal, clinical data of patients with high myopic MNV treated with intravitreal bevacizumab. One-hundred and seventeen eyes of 106 patients were followed from first injection up to 12 years. Outcome measures were best-corrected visual acuity change during follow-up and myopic MNV recurrence. Mean (±SD) baseline best-corrected visual acuity (0.56 ± 0.46 logMAR, 20/80) significantly improved after first treatment (0.33 ± 0.33, 20/50, P < 0.001). At 4 years (n = 86), best-corrected visual acuity was no longer significantly better than at baseline (0.55 ± 0.57, P = 0.30) and continued to deteriorate to 0.84 ± 0.76 (20/125) at 10 years (n = 27). Of the 27 eyes (23%) who reached 10 years of follow-up, 53% developed MNV-related chorioretinal atrophy. The cumulative incidence of recurrent myopic MNV was 34% at 2 years and 59% at 5 years. Best-corrected visual acuity decrease in eyes with or without recurrent MNV was similar ( P = 0.58). Patchy chorioretinal atrophy (hazard ratio 3.0, P = 0.02) and subfoveal MNVs (hazard ratio 2.5, P = 0.048) were significantly associated with recurrent MNV. This retrospective myopic MNV study revealed that visual improvement after intravitreal bevacizumab injections was not maintained over time. Macular neovascularization recurrences occurred frequently but did not alter the already poor visual prognosis.

Intra-ocular pressure changes after intravitreal injection of bevacizumab.

To evaluate the short-term and sustained intraocular pressure changes after intravitreal bevacizumab in patients with diabetic retinopathy. The quasi-experimental study was conducted at the District Headquarter Teaching Hospital, Gujranwala, Pakistan, from January to December 2020, and comprised diabetic patients of either gender aged 18-60 years with indication for intravitreal bevacizumab. Intraocular pressure was measured at 5, 10 and 30 minutes for short-term elevation, and the patients were followed up weekly for one month to record any sustained elevation in intraocular pressure. Data was analysed using SPSS 25. Of the 42 patients, 20(47.61%) were male and 22(52.38%) were female. The overall mean age was 52.4±5.7 years. Intraocular pressure increased significantly in the short term post-injection (p<0.001), while the difference was not significant in the weekly check-ups (p=0.264). There was short-term rise in intraocular pressure after intravitreal bevacizumab, but no sustained elevation was noted over the following month.

Impact of intravitreal ranibizumab, aflibercept and bevacizumab on retinal ganglion cell and nerve fibre layer thickness in Neovascular age-related macular degeneration.

To compare the effects of monotherapy with intravitreal ranibizumab, aflibercept and bevacizumab on retinal ganglion cell layer (RGCL) and retinal nerve fibre layer (RNFL) in patients with naïve neovascular age-related macular degeneration (nAMD). This is a retrospective cohort study with three-groups comparison. 83 patients and 97 eyes on continuous monotherapy with an intravitreal anti-vascular endothelial growth factor (anti-VEGF) were followed for 24 months and divided into three groups according to anti-VEGF (aflibercept: 25 eyes, ranibizumab: 34 eyes, bevacizumab: 38 eyes). Main outcome measures included: RGCL and RNFL thickness, best corrected visual acuity (BCVA), central macular thickness (CMT), macular volume (MV) and the presence of intraretinal fluids (IRF), subretinal fluids (SRF) and retinal pigment epithelial atrophy (RPE-atrophy). All outcome measures were recorded at the time of the first injection, 1 and 2 years after treatment and compared longitudinally and between groups. The mean age was 79 ± 7 years. The RGCL thickness, MV, CMT and the presence of IRF and SRF decreased significantly within all three medication groups (p < 0.05 for all) with no significant difference between groups over the 2-year follow-up period (p > 0.10 for all). The decrease in RNFL thickness was not significant within or between the groups after a 2-year follow-up (p > 0.055 for all). RPE-atrophy increased significantly after 2 years in all three groups (p < 0.028 for all) with no significant difference between groups at all three time points (p > 0.307 for all). BCVA was comparable between the three groups over the 2-year follow-up period (p > 0.22 for all). Monotherapy with intravitreal aflibercept, bevacizumab and ranibizumab was associated with comparable significant decreases in RGCL thickness, CMT, MV, IRF and SRF in naïve nAMD patients during the first 2 years of treatment. Furthermore, no significant differences either in BCVA or RNFL thickness were observed between the three intravitreal anti-VEFGs during the first 2 years of treatment.

Pulmonary function in school-age children following intravitreal injection of bevacizumab for retinopathy of prematurity

The effect of anti-vascular endothelial growth factor on neonatal lung development was inconclusive. To evaluate pulmonary function in school-age children who have received intravitreal bevacizumab (IVB) for retinopathy of prematurity (ROP), this study included 118 school-aged children who were grouped into three groups: full-term control children (group 1), preterm children who had not received IVB treatment (group 2) and preterm children with ROP who had received IVB treatment (group 3). Pulmonary function was measured by spirometry and impulse oscillometry. Pulmonary function was significantly better in group 1 than in groups 2 and 3 (all p < 0.05 in forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1), forced expiratory flow between 25 and 75% of FVC (FEF25–75), and respiratory resistance at 5 Hz and difference between respiratory resistance at 5 and 20 Hz (R5-R20). There were no statistically significant differences between group 2 and group 3 in all pulmonary function parameters, including FVC, FEV1, ratio of FEV1 to FVC, FEF25-75, R5, R20, R5–R20, and respiratory reactance at 5 Hz. In conclusion, our study revealed that preterm infants receiving IVB for ROP had comparable pulmonary function at school age to their preterm peers who had not received IVB treatment.

RISK OF INTRAOCULAR INFLAMMATION AFTER INJECTION OF ANTIVASCULAR ENDOTHELIAL GROWTH FACTOR AGENTS: A Meta-analysis.

This meta-analysis investigates the incidence of intraocular inflammation (IOI) after intravitreal antivascular endothelial growth factor injections in neovascular age-related macular degeneration. A systematic search was performed on Ovid MEDLINE, Embase, and Cochrane Central from January 2005 to April 2021. Randomized controlled trials comparing IOI after intravitreal bevacizumab, ranibizumab, brolucizumab, or aflibercept in neovascular age-related macular degeneration were included. Primary outcomes were sight-threatening IOI, final best-corrected visual acuity, and change in best-corrected visual acuity from baseline. Secondary outcomes included the incidence of other IOI events. Meta-analysis was performed using a random-effects model. Overall, 11,460 unique studies were screened, of which 14 randomized controlled trials and 6,759 eyes at baseline were included. There was no difference between agents for the risk of endophthalmitis and retinal vascular occlusion. Compared with aflibercept, brolucizumab had a higher incidence of generalized IOI (risk ratio = 6.24, 95% confidence interval = [1.40-27.90]) and vitreous haze/floaters (risk ratio = 1.64, 95% confidence interval = [1.00-2.67]). There were no significant differences between comparators for other secondary end points. There was no difference in the risk of severe sight-threatening IOI outcomes between intravitreal antivascular endothelial growth factor agents. There was a significantly higher risk of generalized IOI after brolucizumab relative to aflibercept. Our results alongside other recent safety findings suggest the need for further investigation in the risk-benefit profile of brolucizumab for the treatment of neovascular age-related macular degeneration.

MULTIMODAL IMAGING OF MULTIFOCAL CHOROIDITIS WITH ADAPTIVE OPTICS OPHTHALMOSCOPY.

To describe longitudinal, anatomical, and functional alterations caused by inflammatory and neovascular lesions of idiopathic multifocal choroiditis/punctate inner choroidopathy using adaptive optics imaging and microperimetry. Longitudinal case study using multiple imaging modalities, including spectral-domain optical coherence tomography, fluorescein angiography, indocyanine green angiography, optical coherence tomography angiography, flood illumination adaptive optics, and microperimetry. A 21-year-old myopic Asian man presented with blurred vision in the right eye. Clinical examination was notable for an isolated hypopigmented, perifoveal lesion in each eye. Multimodal imaging showed inflammatory lesions in the outer retina, retina pigment epithelium, and inner choroid lesions of both eyes. The right eye additionally exhibited active Type-2 macular neovascularization with loss of cone mosaic regularity that was associated with reduced sensitivity on microperimetry. The clinical picture was consistent with multifocal choroiditis/punctate inner choroidopathy. The patient was treated with oral steroids and three injections of intravitreal bevacizumab in the right eye. After therapy, imaging showed reestablishment of the cone mosaic on flood illumination adaptive optics and improvement in sensitivity on microperimetry. Adaptive optics imaging and microperimetry may detect biomarkers that help to characterize the nature and activity of multifocal choroiditis lesions and to help monitor response to therapy. With timely intervention, structural abnormalities in the outer retina and choroid can be treated, and anatomical improvements precede improvements in visual function.

Quantitative vascular outgrowth and anatomic and refractive outcomes of eyes treated with bevacizumab in posterior zone Ⅰ.

To report the anatomic and refractive outcomes and retinal vascular outgrowth in eyes with posterior zone Ⅰ retinopathy of prematurity (ROP) treated with intravitreal bevacizumab (IVB). Thirty-eight eyes of 21 infants treated with IVB for type 1 and aggressive-ROP, and whose posterior border of retinal vascularization was shorter than the optic disc-to-fovea distance were defined as posterior zone Ⅰ and included in the study. Nine eyes of five infants whose follow-up time was lower than four months were accepted as insufficient for clinical outcomes. Additional treatment(s) had been performed up to 60 weeks postmenstrual age (PMA) in 10 of 29 eyes whose follow-up were higher than four months. Macula was attached at the final examination in all eyes with > 4 months follow-up. Anatomical outcome of two eyes of one infant was accepted as unfavorable whose routine follow-up was interrupted after successful initial treatment and who was presented with straightening of the temporal vascular arcade and residual fibrovascular tractional bands on the temporal periphery. The mean progression of temporal retinal vascularization was 3.6 ± 2.0 horizontal disc diameters (DD) within 7.3 weeks and 5.1 ± 2.5 horizontal DD within 69.1 weeks in the short-term (n=15) and long-term evaluated eyes (n=21), respectively. The mean spherical equivalent was -4.1 diopters at a mean age of 21 months (n=28). A favorable outcome had been achieved in almost all bevacizumab-treated eyes, but additional treatments were required. Significant progression of retinal vascularization was detected even in the eyes with short follow-up.

Choroidal neovascularization caused by angioid streaks: seven-year follow-up

Angioid streaks are irregular lines that radiate away from the optic disc to the retinal periphery, lying deep into the retina. They indicate the breaks in the calcified Bruch’s membrane. The most common complication of angioid streaks is choroidal neovascularization. They appear primarily bilaterally and are asymmetrical in nature.We report a 29-year-old man with choroidal neovascularization caused by angioid streaks. The study emphasizes seven years of follow-up of the disease treated with intravitreal bevacizumab and aflibercept injections. There were no injection related complications. Anti-VEGF treatment can help the clinician to stabilize the disease and achieve gradual progression. Nonetheless, it cannot help to prevent significant vision loss in long-term follow-up in all cases.

The Risk of Non-arteritic Ischemic Optic Neuropathy Post-intravitreal Bevacizumab Injection.

To report the incidence of non-arteritic ischemic optic neuropathy in diabetic patients treated with intravitreal bevacizumab injection. A prospective comparative analytic study was done in the King Hussein Medical Center during the period between June 2020 and June 2021. Inclusion criteria included diabetic patients who attended a retina clinic. Exclusion criteria included patients with pre-existing ischemic optic neuropathy. Patients were divided into two groups. The first group included diabetic patients who did not require bevacizumab injection and were treated either with follow-up visits or pan-retinal photocoagulation, and the second group included patients who were treated with intravitreal bevacizumab. Patients were followed up for a period of one year. Data collected in two groups included the total number of patients and the number of patients with non-arteritic ischemic optic neuropathy. Results were compared in both groups. A P-value was used to study the statistical significance and was considered to be statistically significant if ≤0.05. The mean age for patients in group 1 was 64.3 years, with a male to female ratio of 1.1 to 1. In group 2, the mean age was 66.2 years, with a male to female ratio of 1.2 to 1. The total number of patients in group 1 was 7375, among whom 68 patients had non-arteritic ischemic optic neuropathy. While in group 2, the total number was 2468 and 49 of them had non-arteritic ischemic optic neuropathy. Most cases of non-arteritic ischemic optic neuropathy were seen in patients who had received three or more injections. Conclusion: Intravitreal bevacizumab in diabetic patients is considered a risk factor for the development of non-arteritic ischemic optic neuropathy, especially in patients receiving more than three injections.

Real-Life Efficacy of Bevacizumab Treatment for Macular Edema Secondary to Central Retinal Vein Occlusion according to Pro Re Nata or Treat-and-Extend Regimen in Eyes with or without Epiretinal Membrane.

Purpose To present real-life data of patients with macular edema (ME) secondary to central retinal vein occlusion (CRVO) treated with bevacizumab (BVZ); determine the possible influence of epiretinal membrane (ERM) on treatment efficacy; and compare treatment outcomes in a treat-and-extend regimen (TER) versus pro re nata (PRN). Methods We carried out a retrospective analysis of 58 eyes (56 patients) with new-onset CRVO treated only with intravitreal bevacizumab according to TER or PRN. Outcome measures were best-corrected visual acuity (BCVA) and central retinal thickness (CRT) at baseline and 12 months after the first treatment, number of visits and injections, and presence of ERM confirmed by optical coherence tomography in the first 6 months. Results At 12 months, the mean number of injections was 6.3 across all eyes, with significantly more injections given in TER (p < 0.001). Mean CRT improved from 627 μm to 359 μm (p < 0.001) in all eyes, with improvement noted in TER (p < 0.001), PRN (p < 0.001), ERM (p=0.003), and non-ERM (p < 0.001) subgroups. The mean BCVA gain was +13.6 letters, and the mean BCVA improved from 0.81 to 0.54 LogMAR (p < 0.001) in all eyes. BCVA improvement from baseline was significant in TER (p < 0.001) and non-ERM (p < 0.001) but not in PRN (p=0.08) or ERM (p=0.2) subgroups. Seven eyes, all receiving PRN treatment, developed neovascularization. Conclusions Intravitreal bevacizumab according to either PRN or TER resolved edema and stabilized vision in the first 12 months, with TER yielding significant visual improvement and avoiding neovascular complications. ERM had no influence on bevacizumab efficacy in reducing ME in CRVO during 12 months of treatment.

STRUCTURAL OUTCOME AFTER SURGERY FOR STAGE 5 RETINOPATHY OF PREMATURITY BASED ON THE NEW INTERNATIONAL CLASSIFICATION: ICROP 3.

This study investigated the outcomes of vitrectomy for Stage 5 retinopathy of prematurity (ROP) based on the International Classification of Retinopathy of Prematurity third edition, in which Stage 5 ROP is divided into three subgroups. Fifty-four eyes of 34 patients with Stage 5 ROP who underwent vitrectomy between 2004 and 2020 were retrospectively analyzed. Data including sex, gestational age and weight at birth, International Classification of Retinopathy of Prematurity 3 subcategories, perioperative use of intravitreal bevacizumab injection and laser photocoagulation, surgical procedure and complications, final retinal reattachment, and follow-up period were collected. Complete retinal reattachment was achieved in 16 eyes (88.9%) with Stage 5A and 13 eyes (39.4%) with Stage 5B ( P = 0.0003, Wilcoxon rank-sum test). Three patients with Stage 5C were considered inoperable. Postoperative anatomical failure was significantly associated with stage (Stage 5B vs. 5A; odds ratio, 17.986; 95% confidence interval, 3.712-148.502; P = 0.0001, multivariate logistic regression analysis). Intraoperative intravitreal bevacizumab was significantly associated with lower postoperative incidence of vitreous hemorrhage and glaucoma ( P = 0.041, chi-square test). Staging of preoperative anatomical features based on International Classification of Retinopathy of Prematurity 3 is a useful predictor for final anatomical success. Intraoperative intravitreal bevacizumab might reduce postoperative complication risks.

EFFECTS OF INTRAVITREAL BEVACIZUMAB THERAPY ON GLOMERULAR FILTRATION RATES IN PATIENTS TREATED FOR PROLIFERATIVE DIABETIC RETINOPATHY.

To assess whether the repeated use of intravitreal bevacizumab injections in treatment of proliferative diabetic retinopathy is associated with a long-term decline in the glomerular filtration rate (GFR). Three hundred charts were retrospectively reviewed, of which 60 patients met the criteria for inclusion. The criteria were as follows: reception of at least one bevacizumab injection, baseline GFR before initial bevacizumab injection, and end GFR 6 to 24 months after baseline. Analysis controlled for time between baseline and end GFR measurements, blood pressure, hemoglobin A1C, race, sex, age, and use of an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker. Significance testing was performed with step-wise multiple linear regression. The significance threshold was 5%, and all tests were two-sided. Patients received a range of 1 to 17 injections (average 3.6). The average baseline GFR was 76 ± 38 mL/minute, and the end GFR was 63 ± 39 mL/min. The number of injections patients received was not associated with end GFR ( P = 0.72), GFR reduction ( P = 0.88), or percent GFR reduction ( P = 0.49). Increased number of intravitreal bevacizumab injections at therapeutic dosage was not associated with reduced GFR in patients with proliferative diabetic retinopathy. This study supports that intravitreal antivascular endothelial growth factor agents are renally safe.

Neovascular glaucoma in atypical central serous chorioretinopathy and pachychoroid disease

We report an atypical central serous chorioretinopathy (CSCR) with pachychoroid disease and consequent recalcitrant neovascular glaucoma (NVG). A 45-year-old man with persistent subretinal fluid, pachychoroid and bilateral large areas of capillary nonperfusion exudative detachment, and CSCR presented with raised intraocular pressure (IOP) and neovascular glaucoma. Failure after trabeculectomy with mitomycin-C mandated the implantation of Ahmed glaucoma valve followed by two epiconjunctival MMC applications over the AGV plate/bleb in the hypertensive phase. He was also started on 25 mg oral eplerenone twice a day for the first month, followed by 25 mg once a day over the next two months, followed by intravitreal bevacizumab injection. The retinal neovascularization regressed along with normalization of IOP at over eight months follow-up.