Predictors of Disease Activity After Anti-VEGF Treatment for Neovascular Age-Related Macular Degeneration Using Real-World Data from the PROOF Study.

INTRODUCTION: The aim of this study was to investigate the predictive factors for persistent disease activity following anti-vascular endothelial growth factors (anti-VEGF) and their long-term effects in patients to be treated for neovascular age-related macular degeneration (nAMD) under real-world conditions. METHODS: Retrospective data analysis of the PROOF study, a multi-center real-world retrospective chart review conducted across Korea in patients with nAMD included treatment-naive patients with nAMD who received first anti-VEGF (ranibizumab, bevacizumab, or aflibercept) between January 2017 and March 2019 was performed. All 600 patients (cohort 1) had a minimum follow-up of 12 months of which 453 patients (cohort 2) were followed-up for 24 months from baseline. RESULTS: At month 12 after anti-VEGF therapy, 58.10% (95% confidence interval [CI]: 54.09, 62.12) of patients and at month 24, 66.02% of patients continued to have persistent retinal fluid. At both months 12 and 24, predictive factors for persistent disease activity were fibrovascular pigment epithelial detachments (PED) (P = 0.0494) and retinal fluid at month 3 after loading phase (P = 0.0082). The mean changes in visual acuity were + 6.2, + 10.1, and + 13.3 letters and in the central subfield thickness were - 79.1 µm, - 96.3 µm, and - 134.4 µm at 12 months from baseline, in the bevacizumab, aflibercept, and ranibizumab groups, respectively. CONCLUSIONS: The presence of retinal fluid after loading phase and fibrovascular PED were predictors of persistent disease activity after at least 1 year of anti-VEGF treatment.

Efficacy of ranibizumab and aflibercept on reducing maximum diameter of largest cyst in diabetic cystoid macular edema: MARMASIA study group.

PURPOSE: This study aimed to compare the effect of intravitreal aflibercept (IVA) and ranibizumab (IVR) on the maximal diameter of the largest intraretinal cyst (mdIRC), indicating chronicity in patients with diabetic cystoid macular edema (CME). METHODS: This retrospective, comparative study included a subgroup of patients from the MARMASIA Study with treatment-naïve diabetic CME who had IVA (IVA group) or IVR (IVR group) on a pro re nata regimen after a loading dose of 3-monthly injections and followed-up for 24 months. Best-corrected visual acuity (logMAR), central macular thickness (CMT, µm), and mdIRC (µm) and their changes during the study period in the IVA and IVR groups were compared. RESULTS: A total of 175 eyes (65 [37.1%] in IVA and 110 [62.9%] in IVR group) of 113 patients were included in the study analysis. Both groups had statistically significant improvements in BCVA and CMT during the follow-up (p < 0.05 for all), which were comparable between the groups at each time point. However, the mean reduction in mdIRCs was consistently and significantly higher in the IVA group compared to the IVR group at each follow-up examination (F[1, 3.52] = 6.93, p = 0.009). CONCLUSION: IVA seems to have a greater impact in reducing cyst sizes than IVR in diabetic CME.

Endophthalmitis in Eyes Treated with the Port Delivery System with Ranibizumab: Summary of Cases during Clinical Trial Development.

PURPOSE: The Port Delivery System with ranibizumab (PDS) is approved in the United States for neovascular age-related macular degeneration. The United States Prescribing Information has a Boxed Warning for endophthalmitis and reports the incidence rate in patients developing endophthalmitis after receiving the PDS compared with monthly intravitreal ranibizumab. Endophthalmitis cases noted in the Boxed Warning, treatment outcomes, potential contributing factors, and potential mitigations are summarized. DESIGN: Retrospective review of endophthalmitis cases in PDS-treated patients in the phase II Ladder (NCT02510794) and phase III Archway (NCT03677934) and Portal (NCT03683251) trials. PARTICIPANTS: Endophthalmitis cases in the pooled all-PDS safety population (N = 555) including PDS patients in Ladder, Archway, or Portal. METHODS: Ladder patients received PDS (10, 40, or 100 mg/ml) with pro re nata refill-exchanges. Archway patients received PDS 100 mg/ml with fixed refill-exchanges every 24 weeks (PDS Q24W). Portal patients received PDS Q24W from day 1. MAIN OUTCOME MEASURES: Clinical features, management, and visual outcomes were summarized. Cases were summarized by date of PDS implant and/or refill, other prior invasive procedures/refills, and preceding/concurrent conjunctival complications. RESULTS: Twelve endophthalmitis events were reported in 11 patients (11/555 [2.0%]) through March 12, 2021. All were cultured (3 were culture positive) and treated with intravitreal antibiotics. Two cases (2/555 [0.4%]) occurred in the immediate postoperative period (days 5 and 6). Nine cases occurred later (day range: 57-853), including 4 before the first refill-exchange (day range: 57-161). Five patients received between 1 and 11 refill-exchanges before the event (onset: 6-168 days after last refill-exchange). Seven cases (7/11 [63.6%]) had preceding/concurrent conjunctival complications. At last follow-up, 7 patients recovered vision to study baseline levels or ≥20/40; 4 patients experienced vision loss of ≥15 ETDRS letters. CONCLUSIONS: Endophthalmitis is a serious complication that can endanger vision after any ocular procedure, including PDS implantation. Most, but not all, of this limited series of endophthalmitis cases were late onset, associated with conjunctival breach, and recovered vision with treatment. Meticulous attention to PDS surgical techniques with vigilant monitoring of conjunctiva during follow-up may minimize risk of endophthalmitis. Prompt treatment is critical for optimizing patient outcomes. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Cost-effectiveness Analysis of Ranibizumab Biosimilar for Neovascular Age-Related Macular Degeneration and its Subtypes from the Societal and Patient Perspectives in Japan.

INTRODUCTION: This study evaluated the cost-effectiveness of anti-vascular endothelial growth factor (VEGF) therapies for subtypes of neovascular age-related macular degeneration (nAMD) from the societal perspective, and for any nAMD from the patient perspective in Japan. METHODS: A Markov model was developed to simulate the lifetime transitions of a cohort of patients with nAMD through various health states based on the involvement of nAMD, the treatment status, and decimal best-corrected visual acuity. Ranibizumab biosimilar was compared with aflibercept from the societal perspective regardless of treatment regimen for the analysis of three subtypes (typical nAMD, polypoidal choroidal vasculopathy (PCV), and retinal angiomatous proliferation (RAP)). Two analyses from the patient perspective focusing on the treat-and-extend regimens were performed, one with a cap on patients' copayments and one without. Ranibizumab biosimilar was compared with branded ranibizumab, aflibercept, aflibercept as the loading dose switching to ranibizumab biosimilar during maintenance (aflibercept switching to ranibizumab biosimilar), and best supportive care (BSC), for patients with any nAMD. RESULTS: In the subtype analyses, ranibizumab biosimilar when compared with aflibercept resulted in incremental quality-adjusted life years (QALYs) of - 0.015, 0.026, and 0.009, and the incremental costs of Japanese yen (JPY) - 50,447, JPY - 997,243, and JPY - 1,286,570 for typical nAMD, PCV, and RAP, respectively. From the patient perspective, ranibizumab biosimilar had incremental QALYs of 0.015, 0.009, and 0.307, compared with aflibercept, aflibercept switching to ranibizumab biosimilar, and BSC, respectively. The incremental costs for ranibizumab biosimilar over a patient lifetime excluding the cap on copayment were estimated to be JPY - 138,948, JPY - 391,935, JPY - 209,099, and JPY - 6,377,345, compared with branded ranibizumab, aflibercept, aflibercept switching to ranibizumab biosimilar, and BSC, respectively. CONCLUSIONS: Ranibizumab biosimilar was demonstrated as a cost-saving option compared to aflibercept across all subtypes of nAMD, irrespective of the perspectives considered.

Impact of the Nationwide Avastin Ban at a Tertiary Eye Care Hospital in Pakistan.

OBJECTIVE:  To report the impact of a 10-week-long nationwide ban on intra-vitreal bevacizumab (IVB) injection (Avastin®) at a tertiary care hospital in Pakistan. METHODS: This was a single-center, retrospective, cohort study. Patients scheduled for IVB injections from October 25, 2023 to October 29, 2023 who arrived in OPD between November 28, 2023 and December 15, 2023 for their assessment were included in this study. RESULTS: Among the identified 412 patients, only 103 met the inclusion criteria. The mean age was 59.35 ± 9.5 (mean ± SD). About 60.2% were male (n = 62). Diabetic macular edema (DME) was the most common indication (n = 71, 68.9%). The mean total duration of treatment delay was 81.67 ± 17.15 days. While the delay due to the Avastin® ban was 67.47 ± 4.8 days. Eyes that had not received any prior injections were 46 (44.7%) while others had received at least 1 (n = 43, 41.7%) or 2 injections (n = 14, 13.6%) before. Mean central macular thickness (CMT) before and after treatment delay was 362.7 ± 113.4 µm and 398.38 ± 124 µm (p < 0.05), respectively. Among 20 patients with vitreous hemorrhage (VH), 14 patients showed marked improvement (70%), 5 showed no change in severity (20%) and 1 (5%) had further worsening. CMT difference was strongly correlated with the total duration of treatment delay (p < 0.01) and with the number of injections (p < 0.01). CONCLUSION: The nationwide ban on Avastin® heightened the severity of disease in the patients highlighting the delicate balance between safety precautions and timely access to essential medical interventions.

Comparison of ranibizumab and conbercept treatment in type 1 prethreshold retinopathy of prematurity in zone II.

PURPOSE: The treatment with anti-VEGF for Retinopathy of prematurity (ROP) has already been widely applied in clinics even though there are still many concerns about this treatment. In this project we investigated the clinical outcomes of intra-vitreous conbercept (IVC) and ranibizumab (IVR) injection for treating type 1 prethreshold ROP in Zone II. METHODS: The data of ROP infants receiving IVR or IVC from January 2017 to March 2020 who were followed up for at least 12 months in our hospital was studied in the present retrospective study. Regression, reactivation, complications, and ocular biological parameters were evaluated. RESULTS: One hundred twenty-five eyes (64 infants) in IVC group and 229 eyes (117 infants) in IVR group were observed in the study. All infants showed good response to the two anti-VEGF agents. No eyes deteriorated during the observation. No significant difference was found between the two groups as to the regression within one week and one month, the reactivation rate, and the retreatment interval (p > 0.05) whereas retinal complete vascularization rate at 6 mons after the initial treatment and mean completion time of retinal vascularization after initial injection showed significant difference (p < 0.05). At 12 mons PMA the ocular parameters also presented no statistical difference between the two treated groups (p > 0.05). However, the ocular showed slight myopic tendency with the anti-VEGF treatment when compared to the control group (p < 0.05) whereas there was no statistical difference revealed between the two treated groups (p > 0.05). CONCLUSIONS: Both conbercept and ranibizumab for treating type 1 prethreshold ROP in Zone II are safe and effective. They had little effect on the development of ocular whereas there was a slight tendency of myopia after the treatment.

Intravitreal Antiangiogenic Treatment for Diabetic Retinopathy: A Mexican Real-Life Scenario Experience.

The objective of this study was to analyze the effectiveness of two intravitreal antiangiogenic drugs, ranibizumab and aflibercept, in a Mexican population over a period of 5 years, evaluating the improvement in visual acuity (VA) and central retinal thickness (CRT) in a real-world scenario. This is a retrospective study with subjects diagnosed with diabetic retinopathy (DR), proliferative diabetic retinopathy (PDR), and diabetic macular edema (DME) receiving intravitreal injections of ranibizumab and/or aflibercept. In this study, we analyzed 588 eyes of 294 patients who received intravitreal antiangiogenic injections. The results showed an improvement regardless of antiangiogenic treatment or diagnosis in both VA and CRT. We found that both aflibercept and ranibizumab improved VA, while subjects with DME responded less to antiangiogenic treatment (p < 0.05), and that this difference did not correspond to the CRT measured by OCT. These results support evidence that intravitreal antiangiogenic medications are effective for ophthalmic complications of diabetes in our population; however, damage to visual structures is not reversed in most patients. And that the perception by the patient (VA) and that of the ophthalmologist (CRT) do not completely correlate in our study.

One-Year Outcome of Intravitreal Injection of Ranibizumab Biosimilar for Myopic Choroidal Neovascularization in Japanese Patients.

Objectives: To evaluate the one-year outcomes of intravitreal ranibizumab biosimilar (RBZ-BS) injections for myopic choroidal neovascularization (mCNV) in Japanese patients. Methods: Twenty-one patients (mean age 69.0 years; 4 males, 17 females) with high myopia and mCNV were retrospectively reviewed. Twelve were treatment-naïve, and nine had previous anti-VEGF treatments. Efficacy measures included best-corrected visual acuity (BCVA) and central macular thickness (CMT). Results: The treatment-naïve group showed significant BCVA improvement from 0.55 ± 0.34 at baseline to 0.24 ± 0.28 at 12 months. The previously treated group had no significant BCVA changes. CMT significantly decreased in both groups: from 295.3 ± 105.2 µm to 207.3 ± 63.0 µm in the treatment-naïve group, and from 196.1 ± 62.0 µm to 147.2 ± 50.1 µm in the previously treated group. Dry macula rates were high: 83% at 3 months and 83% at 12 months in the treatment-naïve group, and 67% at 3 months and 89% at 12 months in the previously treated group. No adverse events were reported. Conclusions: These findings indicate that RBZ-BS is an effective and safe treatment for mCNV, particularly in treatment-naïve patients. The use of RBZ-BS offers a cost-effective alternative to original ranibizumab, reducing financial burdens while maintaining high therapeutic efficacy. Further studies with larger sample sizes and longer follow-up periods are needed to confirm these results and evaluate long-term outcomes and cost-effectiveness.

Systematic Literature Reviews Comparing the Long-Term Safety Outcomes for the Port Delivery System with Ranibizumab (PDS) Versus Other Ocular Implants.

OBJECTIVES: To determine whether the types and rates of post-surgical complications associated with the Port Delivery System with ranibizumab (PDS) are comparable with those reported for other ocular implants that cross the sclera. METHODS: Systematic literature reviews were conducted to determine the long-term (≥ 18-month) safety of ocular implants that cross the sclera in clinical trials and real-world studies. Complication types and rates were compared with those reported for the PDS in phase III clinical trials (Archway, Pagoda, and Pavilion). RESULTS: Sixteen clinical trials (24 publications) and 43 real-world studies were identified reporting 30 complications in eyes with 15 implant types and 8 ocular diseases. Implants were associated with an acceptable, well-characterized safety profile, with most complications resolving spontaneously or with treatment. Device-related complications were reported in 0.7% (0.0-5.0%) of study eyes in clinical trials and 1.3% (0.0-14.5%) of eyes in real-world studies. Rates of conjunctival complications were 2.1% (0.0-22.8%) and 2.2% (0.9-4.6%), respectively. The overall types and rates of adverse events of special interest reported for the PDS in phase III trials (cataract, conjunctival bleb, vitreous hemorrhage, conjunctival erosion, conjunctival retraction, endophthalmitis, implant dislocation, retinal detachment, and hyphema) were within the ranges reported for other ocular implants. CONCLUSIONS: The rates of complications reported in phase III clinical trials for the PDS were within the ranges reported for other ocular implants that cross the sclera. This suggests that the long-term safety of the PDS is consistent with other ocular devices established in ophthalmology clinical practice. TRIAL REGISTRATION: PROSPERO international prospective register of systematic reviews: CRD5202234129, CRD42022343129.

Comparison of Single-Treatment Efficacy of Bevacizumab and Ranibizumab for Retinopathy of Prematurity.

BACKGROUND: Retinopathy of prematurity (ROP) is a significant cause of blindness in infants. Appropriate therapeutic intervention is essential because retinal detachment due to the progression of ROP is critical to visual function. The intravitreal injection of anti-vascular endothelial growth factor (VEGF) agents has been increasingly applied to inhibit the development and progression of ROP. In this study, we compared the efficacy of single intravitreal bevacizumab (IVB) and ranibizumab (IVR) injections for the treatment of ROP. METHODS: A total of 39 eyes in 21 patients with severe ROP and IVB (15 eyes of 8 patients) and IVR (24 eyes of 13 patients) were retrospectively reviewed. Patient background, the severity of ROP, and the percentage of cases in which ROP regressed without additional treatment were compared between the two groups. RESULTS: Patient background and ROP severity were not significantly different between the two groups. Recurrence was observed in one eye of one patient in the IVB group, and thirteen eyes in seven patients in the IVR group required additional laser photocoagulation, which was significantly different in the two groups (p < 0.01, Fisher's exact test). In the IVR group, two eyes of two patients underwent vitreous surgery. CONCLUSION: Compared with IVR, IVB is likely to control the severity of ROP with a single treatment.

Multimodal imaging to distinguish microvascular and morphological changes in retinal vein occlusion after intravitreal ranibizumab with or without triamcinolone acetonide injection.

BACKGROUND: The study was designed to investigate microvascular and morphological changes in retinal vein occlusion (RVO) using multimodal imaging after intravitreal ranibizumab (IVR) with or without triamcinolone acetonide (IVTA) injections. METHODS: This was a retrospective and observational study. Fifty patients (52 eyes) diagnosed with RVO were enrolled. Best corrected visual acuity (BCVA), ophthalmoscopy, fundus fluorescein angiography (FFA), spectral domain optical coherence tomography (SDOCT), and optical coherence tomography angiography (OCTA) were employed sequentially both before treatment and at the last visit after treatment. RESULTS: The mean logMAR VAs in BRVO eyes decreased significantly after treatment (P = 0.029). OCTA showed there was a significant difference in foveal avascular zone (FAZ) in BRVO eyes (P = 0.024), superificial foveal vessel density in both CRVO (P = 0.0004) and BRVO eyes (P = 0.02155). OCT showed the foveal thickness had significant differences after treatment in both CRVO (P < 0.0001) and BRVO eyes (P = 0.0001). BCVA was associated most commonly with ellipsoid zone integrity (P = 0.022). The BCVA in eyes treated with IVR and IVTA was significantly decreased compared with IVR only in BRVO group (P = 0.021). However, the combination of IVR + IVTA significantly improved intraocular pressure (IOP) compared with IVR only in BRVO group (P = 0.037). CONCLUSION: Both IVR and IVR + IVTA can significantly improve the central vision, macular structure, and functions in BRVO group. Simultaneous IVR with IVTA can significantly increase BCVA compared with IVR only in BRVO group.

Characteristics of retinal vascularization in reactivated retinopathy of prematurity requiring treatment and clinical outcome after reinjection of ranibizumab.

This study aimed to determine whether the state of retinal vascularization after anti-vascular endothelial growth factor (anti-VEGF) injection can help predict the risk of reactivated retinopathy of prematurity (ROP) requiring treatment and whether repeated ranibizumab injection will be effective in such cases. We retrospectively reviewed 24 infants (43 eyes) who received ranibizumab monotherapy between January 2021 and December 2022. All eyes were classified as having non-retreated ROP or retreated ROP. The state of ROP at the time of treatment, the time required for resolution of plus disease, and the extent of vascularization at 4 and 8 weeks after treatment were analyzed. Extent of temporal retinal vascularization was measured with serial fundus images using disc-fovea distance (DF) unit and disc diameter (DD). Reactivated ROP requiring treatment occurred in six infants (25.0%) and ten eyes (23.3%) after ranibizumab treatment. The mean retreatment interval was 9.0 ± 3.3 weeks (range 4-16). In the retreated ROP group, the time required for the resolution of plus disease after primary injection was longer compared to the control group (13.3 days vs 5.2 days), with a mean ROP regression time of 3.4 weeks. All eyes in the retreated ROP showed retinal vascularization < 0.5 DF from the original site at 4 weeks after injection. In 90% of cases with retreated ROP, the extent of vascularization at 8 weeks after injection was within 1 DF from the original ROP site, and all cases showed reactivation in the posterior Zone II area. The extent of retinal neovascularization in the retreated group was an average of 0.7 DD (vs 1.7 DD) and 1.3 DD (vs 3.3 DD) at 4 and 8 weeks after injection, respectively. After ranibizumab retreatment, only one reactivated case with vitreous traction progressed to focal retinal detachment, while all other cases regressed with peripheral vascular development. The continuation of delayed retinal blood vessel development after ≥ 8 weeks may indicate a high likelihood of reactivated ROP requiring treatment. In the absence of vitreous traction, ranibizumab reinjection is likely to be effective in treating reactivated ROP requiring treatment.

Transitioning from Aflibercept to Biosimilar Ranibizumab in Neovascular AMD (The TRANSFORM Trial): A Multicenter Observational Study.

Purpose: This study investigates the efficacy of transitioning patients with neovascular age-related macular degeneration (nAMD) from aflibercept (T1) to biosimilar ranibizumab (T2), an approach not previously documented in literature. Methods: In this multicenter observational study, patients over 50 years of age with nAMD were shifted from intravitreal aflibercept (IVI AFL) to biosimilar ranibizumab (B-RBZ) due to financial constraints. This study employed standardized ophthalmological methods to assess visual acuity (VA), central macular thickness (CMT), and subretinal and intraretinal fluid. Statistical analyses included paired t-tests, Wilcoxon signed-rank tests, and linear regression. Results: A total of 29 eyes (12 males and 17 females) were analyzed. Mean age was 72.55 ±6.43 years. VA improved significantly during T1, with a mean increase from 55.0 ± 10.2 to 70.0 ± 8.5 ETDRS letters at the switch time point (p < 0.01), then a slight decrease to 62.3 ± 8.9 at 12 months (p < 0.05) was noted during T2. The mean CMT decreased notably from 400 ± 50 to 290 ± 45 µm at the switch. The final CMT at 12 months after switching to B-RBZ was 280 ± 40 µm (p < 0.01). There was a significant decrease in the retinal and intra retinal fluid during T1, followed by a gradual increase during T2. A significant correlation (p < 0.05) was noted between the presence of intraretinal fluid and increased injection frequency of B-RBZ. Conclusion: The switch from IVI AFL to IVI B-RBZ in patients with nAMD demonstrated efficacy in maintaining the VA and macular anatomy, with some challenges in fluid management.

Effect of ranibizumab combined with laser photocoagulation in the treatment of diabetic macular edema.

Objective: To explore the clinical effect of ranibizumab combined with laser photocoagulation (LP) in treating diabetic macular edema (DME). Methods: We retrospectively reviewed the clinical data of 118 patients with DME admitted to The Affiliated Eye Hospital of Nanchang University from May 2021 to March 2023. Among them, 38 patients received LP alone (Laser-group), 39 patients received ranibizumab alone (Ranibizumab-group), and 41 patients received LP combined with ranibizumab (Combined-group). The improvement of macular edema (ME), visual acuity, and complications between the groups were compared. Results: The time of ME regression, exudation absorption and fundus hemorrhage absorption in the Combined-group was shorter than in the Laser-group and the Ranibizumab-group (P<0.05). After treatment, the CMT and RNV of the three groups decreased compared to pretreatment levels and were lower in the Combined-group compared to the Laser-group and the Ranibizumab-group (P<0.05). BCVA increased after the treatment in all groups, and was markedly higher in the Combined-group than in the Laser and the Ranibizumab-groups (P<0.05). NO were higher in the Combined-group compared to the Laser-group and the Ranibizumab-group. The post-treatment VEGF levels decreased in all groups, and were significantly lower in the Combined-group compared to the Laser-group and the Ranibizumab-group (P<0.05). The incidence of complications in the Combined-group was lower than in the Laser-group and the Ranibizumab-group (P<0.05). Conclusions: Compared to ranibizumab or LP alone, ranibizumab combined with LP is more effective in reducing ME in patients with DEM, and is associated with fewer complications.

Comparison of Intravitreal Ranibizumab and Laser Photocoagulation in the Treatment of Type I Retinopathy of Prematurity in Malaysia: A One-Year Follow-Up Study.

PURPOSE: This study aimed to evaluate the treatment efficacy, anatomical outcomes, and refractive outcomes of laser photocoagulation (LPC) and intravitreal ranibizumab (IVR) in the treatment of type I retinopathy of prematurity (ROP) at one-year follow-up. METHODS: This is a retrospective study on the treatment of type I ROP and aggressive ROP (A-ROP) using LPC or IVR in three Malaysian hospitals providing pediatric ophthalmology services from January 2019 to December 2021. Information on gestational age, birth weight, ROP zone and stage, and underlying comorbidities was collected. Parameters for evaluating treatment efficacy include the time taken to achieve complete regression, the regression rate, and the reactivation rate. The anatomical and refractive outcomes were evaluated at one year of adjusted age. RESULTS: This study included 92 eyes from 46 infants. Of these, 42 eyes received LPC as the initial treatment, while 50 eyes underwent IVR. A higher percentage of infants with cardiovascular disease were treated with IVR (66.7%) compared to LPC (40%) (p<0.05). However, there were no significant differences in gestational age, birth weight, respiratory distress syndrome, sepsis, or intraventricular hemorrhage between the two treatment groups (p>0.05). Infants treated with LPC had a higher regression rate than those treated with IVR, but they were also significantly more myopic and had worse best-corrected visual acuity (BCVA). Conversely, infants treated with IVR experienced a significantly higher reactivation rate compared to those treated with LPC. Logistic regression analysis showed no significant associations between gestational age, birth weight, plus disease, zone 1 ROP, and the choice of initial treatment with the reactivation of ROP. CONCLUSIONS: Both LPC and IVR effectively treat type I ROP in infants, with IVR yielding superior anatomical and refractive outcomes and LPC offering a lower reactivation rate. Understanding individual patient characteristics is crucial for treatment selection.

Clinical Outcomes and Experiences with Prefilled Syringes Versus Vials for Intravitreal Administration of Anti-VEGF Treatments: A Systematic Review.

INTRODUCTION: Anti-vascular endothelial growth factor (VEGF) agents have been the standard treatment for retinal diseases for almost two decades. These treatments are administered via intravitreal injection using single-use vials or prefilled syringes (PFS). In this systematic review, we evaluate health care resource use and clinical outcomes and experiences with PFS for intravitreal injection of anti-VEGF treatments. METHODS: MEDLINE, EMBASE, and The Cochrane Library were searched from January 1, 2015 to February 8, 2024 to identify literature reporting outcomes regarding procedural efficiency, health care resource use, patient and clinician experiences, and safety for currently approved anti-VEGFs (ranibizumab, aflibercept, brolucizumab) administered using PFS. Comparators were vial-based injections of the same anti-VEGFs. RESULTS: A total of 36 publications met the criteria for inclusion in the systematic literature review; the majority were non-randomized studies, with a small number of reviews, case series, survey studies, and opinion articles. Publications reported that preparation times were significantly shorter for PFS (40.3-57.9 s) versus vials (ranibizumab, 62.8-98.0 s; aflibercept, 71.9-79.5 s), with no differences in product stability between PFS and vials. Clinicians expressed a preference for PFS and thought PFS were faster, easier to use, and had increased safety versus vials. Publications consistently reported significantly lower rates of endophthalmitis per injection with PFS versus vials (ranibizumab PFS, 0-0.02%; aflibercept PFS, 0.01-0.02%; ranibizumab vial, 0.02-0.05%; aflibercept vial, 0.02-0.06%). Four publications reported increased rates of transient vision loss after aflibercept PFS injection versus vial-based injection. No publications reported outcomes regarding health care resource use or patient experiences. CONCLUSION: The available literature supports the increased procedural efficiency of PFS versus vial-based intravitreal injection of anti-VEGFs. PFS are positively perceived by clinicians and have a safety benefit in the form of a decreased risk of endophthalmitis versus vials.

Anti-vascular endothelial growth factor (VEGF) drugs, given by injection into the eye, are commonly used to treat diseases that affect the back of the eye (the retina). Anti-VEGF drugs are provided in small containers (vials) or in syringes that are already filled with the drug (prefilled syringes). When someone is treated with an anti-VEGF drug from a vial, the drug must first be taken from the vial using a needle and syringe, and then injected. When someone is treated with an anti-VEGF drug from a prefilled syringe, the drug is injected directly from the prefilled syringe, i.e., there are fewer steps involved when a prefilled syringe is used. We searched the medical literature to see if there were differences in clinical outcomes and experiences between prefilled syringes and vials when used to inject anti-VEGF drugs. Clinicians spent about 50% less time getting ready for injections when prefilled syringes were used than when vials were used. Clinicians also preferred to use prefilled syringes than vials for injecting anti-VEGF drugs. Clinicians reported that prefilled syringes were easier to use, faster, and safer than vials. Patients who were given injections from prefilled syringes had a lower rate of infection of the inside of the eye (endophthalmitis) than patients who were given injections from vials. These results indicate that using prefilled syringes for injecting drugs into the eye can improve efficiency at ophthalmology clinics and improve safety for patients.

Acute Noninfectious Anterior Ocular Inflammation Following Ranibizumab Biosimilar Intravitreal Injection in a Patient With Recent COVID-19 Vaccination.

Even in the post-coronavirus disease 2019 (COVID-19) era, it is prudent to exercise caution regarding the timing between intravitreal anti-vascular endothelial growth factor (VEGF) injections and COVID-19 vaccinations, as ocular inflammation can occur following both procedures. However, this perspective has not been sufficiently discussed thus far. Herein, we report a case of acute noninfectious anterior ocular inflammation following an intravitreal injection of ranibizumab biosimilar (RBZ BS, Senju Pharmaceuticals, Japan) in a patient recently vaccinated against COVID-19. A 74-year-old male with myopic choroidal neovascularization (CNV) in the left eye was treated with RBZ BS intravitreal injection. He received his fourth COVID-19 vaccination with messenger ribonucleic acid (mRNA)-1273 (Moderna) two days prior to his second RBZ BS intravitreal injection. He reported no systemic symptoms associated with the fourth COVID-19 vaccination. The second RBZ BS intravitreal injection was safely performed without complications. However, a few hours later, he experienced blurred vision without ocular pain in his left eye, a symptom not observed after the first injection. He visited a local ophthalmologic clinic the following day and was subsequently referred to our hospital due to anterior ocular inflammation in the left eye. His vision in the left eye was 0.3 decimal best-corrected visual acuity. Examination revealed non-granulomatous anterior ocular inflammation with 3+ cells and 2+ flare in the left eye. Anterior vitreous inflammation, keratic precipitates, or conjunctivitis was absent. Fundus examination also showed no signs of posterior inflammation. Both fluorescence angiography and indocyanine green angiography revealed staining corresponding to CNV without retinal vasculature leakage. There is nothing abnormal with the right eye based on the examination. Given that the noninfectious ocular inflammation was likely, based on the acute onset of symptoms within less than 24 hours following the RBZ BS intravitreal injection, and the presence of non-granulomatous inflammation only in the anterior segment without ocular pain, betamethasone eye drops four times daily was initiated in the left eye on the first day following the second RBZ BS intravitreal injection. Then, his ocular inflammation improved to mild by the fourth day post-injection. His eye eventually cleared, with no cells or flare in the anterior chamber at five months. Eventually, given the clinical course of good response to only topical steroid therapy, the diagnosis of noninfectious anterior ocular inflammation following RBZ BS in the case of a recent episode of COVID-19 vaccination was retrospectively confirmed. Although this case represents one of the initial instances of noninfectious ocular inflammation following RBZ BS (Senju Pharmaceuticals) administration, sterile ocular inflammation after other intravitreal anti-VEGF therapy has already been well-reported. In addition, given the recent COVID-19 vaccination, the ocular inflammation might be influenced by the vaccination, synergistically leading to vaccine-associated uveitis with similar signs and symptoms. In conclusion, to prevent such a complex situation, it is advisable to consider an adequate interval between COVID-19 vaccination and intravitreal anti-VEGF injections.

Differences between pathologic and non-pathologic high myopia in 4-year outcomes of anti-VEGF therapy for macular neovascularization.

This retrospective observational study aimed to investigate the difference in 4-year outcomes of ranibizumab or aflibercept therapy for macular neovascularization (MNV) with high myopia between pathologic myopia (PM) and non-PM. This study was conducted at Kyoto University Hospital and included consecutive treatment-naïve eyes with active myopic MNV, in which a single intravitreal ranibizumab or aflibercept injection was administered, followed by a pro re nata (PRN) regimen for 4 years. Based on the META-PM study classification, eyes were assigned to the non-PM and PM groups. This study analyzed 118 eyes of 118 patients (non-PM group, 19 eyes; PM group, 99 eyes). Baseline, 1-year, and 2-year best-corrected visual acuity (BCVA) were significantly better in the non-PM group (P = 0.02, 0.01, and 0.02, respectively); however, the 3-year and 4-year BCVA were not. The 4-year BCVA course was similar in both groups. However, the total number of injections over 4 years was significantly higher in the non-PM than in the PM group (4.6 ± 2.6 vs. 2.9 ± 2.6, P = 0.001). Four-year BCVA significantly correlated only with baseline BCVA in both non-PM (P = 0.047, ß = 0.46) and PM groups (P < 0.001, ß = 0.59). In conclusion, over the 4-year observation period, the BCVA course after anti-VEGF therapy for myopic MNV was similar in the eyes with non-PM and those with PM; however, more additional injections in a PRN regimen were required in the eyes with non-PM compared to those with PM. Thus, more frequent and careful follow-up is required for the eyes with non-PM compared with those with PM to maintain long-term BCVA.

Macular Ischemia Changes in Patients with Diabetic Macular Edema Treated with Aflibercept and Ranibizumab.

Τhis study aims to assess changes in the fovea avascular zone (FAZ) in treatment naïve patients receiving aflibercept or ranibizumab injections for diabetic macular edema (DME). Best corrected visual acuity (BCVA) testing, OCT, and OCT-angiography imaging were performed at baseline and 1 month after each injection. Injections of either aflibercept or ranibizumab were administered monthly for 6 consecutive months. FAZ in the superficial (SCP) and the deep capillary plexus (DCP) using OCT angiography was recorded for each visit. Fifty eyes from fifty patients with a mean age of 67.0 ± 10.7 years were included in the study. Twenty-five patients received aflibercept and twenty-five received ranibizumab. BCVA was 40.8 ± 10.0 and increased to 52.1 ± 7.9 ETDRS letters at the last visit (p < 0.001). CRT was 295.6 ± 34.0 at baseline and 247.9 ± 29.7 at the last study visit (p < 0.001). SCP FAZ was 350.6 ± 79.5 µm2 at baseline and 339.0 ± 71.3 µm2 after sox monthly injections (p = 0.132). DCP FAZ was 558.6 ± 199.0 µm2 at baseline and 459.5 ± 156.1 µm2 after six monthly injections (p < 0.001). There was no effect of the choice of ranibizumab or aflibercept on DCP FAZ change (p = 0.277). In conclusion, treatment with 6 monthly injections of ranibizumab and aflibercept led to an increase in BCVA and a decrease in CRT and DCP FAZ area. Both drugs led to an improvement in DCP ischemia.

Supplemental Intravitreal Ranibizumab Injections in Eyes Treated with the Port Delivery System with Ranibizumab in the Archway Trial.

PURPOSE: To determine the proportion and characteristics of eyes with neovascular age-related macular degeneration (nAMD) treated with the Port Delivery System (PDS) with ranibizumab that receive supplemental intravitreal ranibizumab injections because of changes in best-corrected visual acuity (BCVA) or central subfield thickness (CST), or both, and to investigate the safety and efficacy of supplemental injections in eyes with the PDS. DESIGN: Post hoc analyses of data from the phase III, randomized, multicenter, open-label, active-comparator Archway trial (NCT03677934). PARTICIPANTS: Adults with nAMD diagnosed within 9 months of screening previously responsive to anti-VEGF therapy. INTERVENTION: Four hundred eighteen patients were randomized to the PDS with ranibizumab 100 mg/ml with fixed refill-exchanges every 24 weeks (Q24W) or monthly intravitreal ranibizumab 0.5 mg for 96 weeks. RESULTS: Of the 246 eyes treated with the PDS Q24W and assessed for supplemental treatment criteria, the vast majority (94.6%-98.4%) did not receive supplemental treatment during each retreatment interval, with 87.4% not receiving supplemental treatment at any point during the trial. Of the 31 eyes receiving supplemental treatment, 58.1% received 1 injection and 32.3% received 2. At baseline, eyes receiving supplemental treatment were significantly more likely to have thicker retinas (mean CST, 370.5µm vs. 304.4µm; P = 0.0001), subretinal fluid (54.8% vs. 21.2%; P < 0.0001), and larger pigment epithelial detachment height (215.7 µm vs. 175.9 µm; P = 0.003). These features have previously been associated with difficult-to-treat nAMD. Although BCVA and CST generally remained constant throughout the trial in eyes without supplemental treatment, the small number of eyes receiving supplemental treatment on average lost 1 line of vision from baseline to week 96 (mean, -5.7 ETDRS score letters) and CST continued to increase over time. Absolute BCVA at week 96 was similar irrespective of supplemental treatment status (71.1 and 73.7 letters). Best-corrected visual acuity and CST generally improved within 28 days of supplemental treatment. CONCLUSIONS: Although the PDS Q24W effectively maintains vision and retinal stability in most eyes with nAMD, a small proportion of patients with features of difficult-to-treat nAMD may benefit from supplemental intravitreal anti-VEGF injections and initial close monitoring is recommended. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.