Intravitreal Ranibizumab Research Articles

Safety and efficacy of ranibizumab biosimilar (Razumab®) as a cost-effective alternative to the innovator molecule for macular disorders in real-world

: To report the clinical efficacy and safety of the intravitreal ranibizumab biosimilar molecule, Razumab® (IVRz) as an economic alternative to the innovator molecule (Lucentis) in macular diseases under real-world conditions.: A single‑ center, prospective study of 100 consecutive eyes undergoing three-monthly IVRz between April 2020 to March 2021 for a variety of macular disorders including diabetic macular edema (DME), neovascular age‑related macular degeneration (nAMD), retinal vein occlusion (RVO), and myopic choroidal neovascular membrane (mCNVM). The main outcome measures were changes in best-corrected visual acuity (BCVA), central subfield thickness (CST), intraretinal-fluid (IRF), and subretinal-fluid (SRF) along with a safety analysis at weeks 4, 8, and 12 respectively. : Of the 100 eyes of 100 patients undergoing IVRz, a majority had DME (39 eyes; 39%) followed by RVO (34 eyes; 34%), nAMD (21 eyes; 21%), and mCNVM (6 eyes; 6%). Mean BCVA improved from baseline to weeks 4, 8, and 12 (P<0.001). A significant reduction in CST from the baseline was also noted at all the visits (P<0.001). On qualitative analysis, resolution of SRF and IRF was observed in 61.47% and 61.71% of eyes respectively. No serious ocular or systemic adverse events were noted.: Our real-world data suggests that IVRz therapy is safe and efficacious for the management of varied macular pathologies. The cost-effectiveness and systemic and ocular safety of this regulatory-approved biosimilar makes it a suitable alternative to the branded drug. Further comparative studies into the benefit-cost analysis of these biosimilar and branded agents are warranted to better understand the health economics of anti-vascular endothelial growth factor (anti-VEGF) therapy in chorioretinal disorders.

Predictive Factors for Retreatment after Intravitreal Ranibizumab Injection to Treat Type 1 Retinopathy of Prematurity

Purpose: To investigate predictive factors for retreatment after intravitreal ranibizumab injection as first-line treatment for retinopathy of prematurity (ROP).Methods: The medical records of consecutive infants diagnosed with type 1 ROP from 2013 to 2021 who received 0.2 mg intravitreal ranibizumab as their first treatments were retrospectively reviewed. Only eyes with severe ROP were included. Retreatment was performed if eyes again met the criteria for type 1 ROP or presented with stage 3 ROP and the plus sign. Factors around the time of first injection that predicted retreatment were assessed.Results: Intravitreal ranibizumab was injected into 44 eyes of 44 infants. The mean gestational age (GA) and body weight were 27.8 weeks and 1,046.6 g, respectively. Retreatment was required by 21 eyes (47.7%) at an average of 8.9 weeks after the first injection, thus at 37.2 weeks of mean postmenstrual age. The retreatment group exhibited a lower GA (<i>p</i> = 0.036), lower 1 minute (min) (<i>p</i> = 0.014) and 5 min (<i>p</i> = 0.029) Apgar scores, and more quadrants with plus signs (<i>p</i> = 0.044) before the first injections; they also had a longer period of oxygen requirement (<i>p</i> = 0.001), more loss of the plus sign (<i>p</i> = 0.014), and more ROP involution (<i>p</i> = 0.003) after the first injections. The risk of needing retreatment increased with a lower 1 min Apgar score (<i>p</i> = 0.010, odds ratio [OR] = 2.04) and later disappearance of the plus sign (<i>p</i> = 0.013, OR = 1.44) after the first injection.Conclusions: About half of patients with type 1 ROP may require retreatment 2 months after the first ranibizumab injection. Delayed loss of the plus sign increases the risk of retreatment; careful fundus examination is recommended after the first injection.

Risk factors in the development of retinopathy of prematurity: A 10-year retrospective study

ObjectiveTo evaluate Retinopathy of Prematurity (ROP) rate and risk factors in a large cohort of preterm newborns. MethodsSingle center retrospective study. All preterm inborn hospitalized at the Neonatal Intensive Care Unit of the Policlinico of Catania from January 1, 2009 till December 31, 2018, were included.ROP stage and location, treatments required, maternal and infant risk factors were evaluated. ResultsMedical records of 898 preterms were retrospectively examined (mean gestational age 32.9 ± 2.3 weeks). Of them 149 (16.6 %) developed bilateral ROP (92 stage 1, 44 stage 2 and 13 stage 3); 66 (7.3 %) received bilateral laser treatment. Six eyes of three patients affected by zone I ROP 1, with plus persistence 15 days after an optimal laser treatment, also received intravitreal ranibizumab injection. Risk factors for ROP development were gestational age (GA) (p < 0.001), birthweight (p < 0.001), assisted ventilation duration (p < 0.001), multiple birth (p = 0.003), erythropoietin (EPO) administration (p = 0.005) and persistence of tunica vasculosa lentis. The decision-tree analysis showed gestational age as the most significant predictive factor (P < 0.001); secondary predictive factors were EPO administration (p = 0.001) in newborns 29–31 weeks GA and birthweight lower than 2090 g (p < 0.001) in 32–34 weeks GA; in this latter group patent ductus arteriosus (PDA) was a tertiary predictive factor (p = 0.043). ConclusionsIn our study ROP incidence was 16,6 %; 7.3 % of the patients required laser treatment. Besides well-known factors, such as GA and birthweight, other factors like duration of assisted ventilation, EPO, multiple births, PDA, tunica vasculosa lentis persistence should be considered to tailor ophthalmic evaluation and follow-up.

A quantitative sonoelastography evaluation of ocular and periocular elasticity after intravitreal ranibizumab injection

We evaluated changes in ocular and periocular elasticity by ultrasound (US) elastography in intravitreal ranibizumab-treated eyes and the healthy fellow eyes of patients with neovascular AMD. The study was performed on 52 eyes of 26 volunteers who ranged in age from 59 to 89 (mean 72±7.78) years old. The study group consisted of the patients with neovascular AMD treated with intravitreal ranibizumab. The fellow eyes (without choroidal neovascularization) of the study group were selected as the control group. All patients were examined with sonoelastography before intravitreal injection and at 1day, 1week, and 1month after intravitreal injection. All images were acquired with a Toshiba Aplio 500 ultrasound system (Tokyo, Japan) including software with a combined autocorrelation method and a multifrequency linear probe. The elastography values of the anterior vitreous (AV), posterior vitreous (PV), retina-choroid-sclera complex (RCS), retrobulbar fat tissue (RF), optic nerve head (ONH) and retrobulbar optic nerve (RON) were measured in each eye. There were 13 male (50%) and 13 female (50%) participants in our study. Anterior vitreous, posterior vitreous, RCS, retrobulbar fat tissue, ONH, and RON US elastography values were similar in both groups (P˃0.05 for all). On the other hand, there was a positive correlation between the difference between baseline and 1-month PV sonoelastography values and age (r=0.47, P=0.035). A single dose intravitreal Ranibizumab (Lucentis®, Genentech, USA) injection does not alter the elasticity of ocular and periocular structures.

Long-Term Change in Renal Function After Intravitreal Anti-VEGF Treatment for Diabetic Macular Edema: A 2-Year Retrospective Cohort Study.

To investigate the longitudinal changes in renal function and associated factors after intravitreal anti-vascular endothelial growth factor (VEGF) administration in diabetic macular edema (DME). A total of 108 patients who had received intravitreal ranibizumab or aflibercept for DME and had follow-up visits for at least 2years in one hospital were retrospectively enrolled. The estimated glomerular filtration rate (eGFR) at baseline and during the follow-up period and receipt of any renal replacement therapy were recorded. Linear regression and Cox regression models were used to evaluate factors associated with eGFR decline and renal replacement therapy. After intravitreal anti-VEGF treatment, eGFR showed a mean decline of -10.4 ± 23.2% and -16.5 ± 26.4% at months 12 and 24, respectively. Patients in the eGFR > 120mL/min and 15-30mL/min groups had the greatest decline (-32.0 ± 20.6% and -37.4 ± 30.9%, respectively) while those in the 61-90mL/min group had the smallest decline (-4.3 ± 19.7%) in eGFR after the 2-year treatment. One out of 52 patients (1.9%) receiving ranibizumab and five out of 56 patients (8.9%) receiving aflibercept started hemodialysis or peritoneal dialysis within the 2-year follow-up period (P = 0.21). Baseline eGFR correlated with renal replacement therapy after intravitreal anti-VEGF treatment (hazard ratio = 0.879 per increase of 1 in eGFR, P = 0.018). In DME patients receiving intravitreal anti-VEGF treatment, a persistent decline in eGFR was observed during the 2-year treatment course. Patients with extremely high or low eGFR had greater eGFR decline, and those with poor baseline eGFR tended to require dialysis after intravitreal anti-VEGF treatment.

Efficacy of subthreshold micropulse laser photocoagulation therapy versus anti-vascular endothelial growth factor therapy for refractory macular edema secondary to non-ischemic branch retinal vein occlusion.

To assess the efficacy of subthreshold micropulse laser photocoagulation (SMLP) therapy versus anti-vascular endothelial growth factor (anti-VEGF) therapy in patients with refractory macular edema (ME) secondary to non-ischemic branch retinal vein occlusion (BRVO). This single-center, prospective, nonrandomized, case-control trial involved patients with refractory ME that responded poorly to three or more initial anti-VEGF injections. The patients were examined and divided into two groups according to their chosen treatment: the intravitreal ranibizumab (IVR) group and the SMLP group. Both groups were followed up monthly for 12 months. Therapeutic efficacy and safety were assessed throughout the follow-up period. The IVR group comprised 49 eyes, and the SMLP group comprised 45 eyes. The improvements in the optical coherence tomography findings and visual acuity were comparable between the two groups at the final follow-up. The total number of injections was significantly lower in the SMLP than IVR group. No serious adverse events occurred during the study period. SMLP therapy is better for patients with central macular thickness (CMT) of ≤400 μm. For patients with CMT of >400 μm, we advise continuation of anti-VEGF agents to reduce ME followed by application of SMLP therapy when CMT has decreased to ≤400 μm.

Anti-Vascular Endothelial Growth Factor Therapy with or Without Initial Steroid Therapy for Macular Edema in Branch Retinal Vein Occlusion.

In branch retinal vein occlusion (BRVO), administering steroid injections to inhibit expression of inflammatory factors in the first phase of macular edema may reduce recurrence of the edema. The purpose of our study was to investigate the functional and morphological prognosis and frequency of recurrence after injection of an anti-vascular endothelial growth factor (VEGF) with and without initial steroid therapy to treat macular edema with BRVO. Patients with BRVO and macular edema (41 eyes) received intravitreal ranibizumab injection (IRI) alone (IRI group, 21 eyes) or subtenon triamcinolone (STTA) injection and IRI (combination group, 20 eyes). Patients in both groups with recurrent macular edema received further IRI as appropriate. A laser flare meter was used to assess aqueous flare values, and an optical coherence tomography device was used to measure central macular thickness (CMT). Before the first treatment, we obtained samples of aqueous humor and analyzed them by the suspension array method to evaluate VEGF, placental growth factor (PlGF), platelet-derived growth factor (PDGF)-AA, soluble intercellular adhesion molecule (sICAM)-1, monocyte chemoattractant protein 1 (MCP-1), interleukin (IL)-6, IL-8, and interferon-inducible 10-kDa protein (IP-10). The two groups were not significantly different with regard to levels of VEGF, PlGF, PDGF-AA, sICAM-1, MCP-1, IL-6, IL-8, or IP-10. Best-corrected visual acuity, CMT, and aqueous flare value (IRI group, baseline 8.69 ± 4.55 photon counts/ms; combination group, baseline 9.21 ± 3.72 photon counts/ms) improved significantly in both groups without significant intergroup differences. Analyses showed no significant intergroup differences in the mean number of IRIs during the 12-month follow-up, but the proportion of patients without recurrence (ie, who received only one IRI) was significantly higher in the combination group than in the IRI group (P = 0.032). Furthermore, the time to initial recurrence was significantly longer in the combination group than in the IRI group (P = 0.003). These findings suggest that initial STTA injection and IRI may have a synergistic effect in patients with BRVO and macular edema in that they increase the time between anti-VEGF treatments.

Comparison of intravitreal ranibizumab and aflibercept for the treatment of diabetic macular edema: a real-world study.

To compare the visual and anatomic outcomes of intravitreal ranibizumab versus aflibercept in patients with diabetic macular edema (DME) in a real-world study. This is a single-center retrospective comparative study of treatment-naïve patients who received intravitreal ranibizumab or aflibercept administration for DME for at least 12 months on an as needed regimen following three-monthly loading doses. The primary outcomes of the study were the mean change in best-corrected visual acuity (BCVA), central macular thickness (CMT), and central macular volume (CMV). Factors to potentially affect these parameters were also analyzed. A total of 100 eyes (66 patients) were included in the study. Fifty two eyes received ranibizumab and 48 eyes in aflibercept injections. At the end of follow-up, the improvement in mean BCVA was similar in both groups (p = 0.38). While the decrease in mean CMT at the 4th-month visit was significantly higher in the aflibercept-treated group than in the ranibizumab-treated group (p = 0.02), there was no difference between the two groups at the end of the 1-year follow-up (p = 0.25). There was no significant difference between the two groups in terms of change in mean CMV during the follow-up (p = 0.26, p = 0.27 at 4 and 12 months, respectively). The mean number of injections were also similar between groups (4.5 ± 1 vs. 4.6 ± 1.1 respectively, p = 0.63). In a real-world setting, ranibizumab and aflibercept were both found to be effective in the first-line treatment of DME. Patients with DME who received fewer injections in the real-world could achieve visual and anatomical results comparable to randomized controlled trials participants.

Long-term efficacy and complications of intravitreal anti-vascular endothelial growth factor agents combined with ablative therapies in juvenile Coats disease: a five year follow-up study.

To evaluate the long-term safety and efficacy of adjuvant intravitreal anti-VEGF therapy in juvenile Coats disease. This retrospective, observational study included a total of 62 eyes in 62 pediatric patients with juvenile Coats disease treated with intravitreal anti-VEGF agents followed for a mean of 67.08months (ranged from 60 to 93months). All affected eyes were managed initially with one session of ablative treatment plus adjuvant intravitreal anti-VEGF agent (0.5mg/0.05ml ranibizumab or conbercept). Ablative treatment was repeated if telangiectatic retinal vessels were not completely regressed or recurred. Anti-VEGF therapy was repeated if subretinal fluid or macular edema still existed. Treatments above were repeated every 2 to 3months. We reviewed clinical and photographic records of patients including the demographics, clinical characteristics and interventions. At final visit, all 62 affected eyes had partially or completely disease resolution; none progressed to advanced stage namely neovascular glaucoma or phthisis bulbi, respectively. No ocular or systemic side effects related to intravitreal injections were observed during follow-up. In terms of 42 affected eyes that could cooperate with visual examination, best corrected visual acuity improved in 14 (14/42, 33.3%) eyes, stabled in 25 (25/42, 59.5%) eyes, and worsened in 3 (3/42, 7.1%) eyes. In the field of complications, 22 (22/62, 35.5%) eyes developed cataracts; 33 (33/62, 53.2%) eyes developed vitreoretinal fibrosis, of whom 14 (14/33, 42.4%) eyes in the subgroup of stage 3B developed progressive TRD; 40 (40/62, 64.5%) eyes developed subretinal fibrosis. Multivariate regression analysis showed increased clinical stage may be associated with the development of vitreo- and subretinal fibrosis (adjusted odds ratio:16.77,17.59; 95% CI:4.50-62.53, 3.98-77.86, respectively, all P < 0.001). Adjuvant intravitreal ranibizumab or conbercept combined with ablative therapies may be a long-term safe and effective treatment for juvenile Coats disease.

The efficacy of different anti-vascular endothelial growth factor agents, and dexamethasone implant therapy in patients with serous retinal detachment caused by Irvine-Gass syndrome.

The aim of this study is to compare the efficacy of intravitreal aflibercept (IVA), bevacizumab (IVB), ranibizumab (IVR), and dexamethasone implant (IVDI) in the treatment of serous retinal detachment (SRD) caused by Irvine-Gass syndrome (IGS). Retrospective cohort, comparative study. The medical records of 128 eyes with no previous history of intravitreal agents in 128 IGS patients with SRD that received IVA, IVB, IVR, and IVDI monotherapy were retrospectively reviewed. The patients were divided into 4 groups, according to treatment. Patients with recurrence and/or were unresponsive following a course of topical steroids and non-steroidal anti-inflammatory drugs (NSAIDs) were included in the study. Best corrected visual acuity (BCVA), central macular thickness (CMT), subfoveal choroidal thickness (SFCT), and SRD were compared between the 4 treatment groups at baseline, at follow-up months 1, 3, 6, and 12, and at the final follow-up visit. Serous retinal detachment completely resolved in 74%, 45.7%, 66.4%, and 40.8% of the eyes at month 1 (P = 0.042), 87%, 50.9%, 75.8%, and 80.9% at month 3 (p = 0.031), 88.9%, 50.4%, 75.7%, 80.2% at month 6 (p = 0.028), 81.7%, 72.8%, 68.7%, 80.1% at month 12 (p = 0.580), and 100%, 66.4%, 87.9%, 93.2% (p = 0.478) at final follow-up visit in the IVA, IVB, IVR, and IVDI groups, respectively. BCVA was significantly better in the IVA group at all follow-up time points (month 1: p < 0.001; month 3: p < 0.001; month 6: p = 0.002; month 12: p = 0.009, final follow-up visit: p < 0.001). CMT was significantly lower in the IVA group at months 3 (p = 0.008), 6 (p = 0.011), and 12 (p = 0.010), and at the final follow-up visit (p < 0.001). Recurrence was observed after a longer period of time and fewer injections were needed in the IVDI and IVA groups (p < 0.05). Resolution of CME was most rapid in the IVA group (p = 0.032). All intravitreal agents were effective in terms of visual results in the SRD patients; however, eyes treated with IVA and IVDI required fewer injections, as compared to the eyes treated with IVB and IVR. Furthermore, SRD entirely resolved in all eyes in the IVA group at the final follow-up visit.

Evaluation of diabetic macular edema by using optical coherence tomography in patients underwent combined phacoemulsification and intravitreal ranibizumab injection versus patients underwent sequential intravitreal ranibizumab injection and phacoemulsification: an observational study

Purpose To compare combined phacoemulsification and intravitreal Ranibizumab (RBZ) injection versus sequential Intravitreal Raibizumab injection and phacoemulsification on the progression of diabetic macular edema (DME) both clinically (through best corrected visual acuity) and by optical coherence tomography (OCT). Setting and design This observational study was conducted in October 6 University, Faculty of Medicine, Department of Ophthalmology. Patient and methods Patients with non-ischemic diabetic macular edema (DME); along with, clinically significant cataract were randomly divided into two groups. Both groups received three intravitreal 0.5 mg/0.05 ml RBZ injections on monthly basis. Group (I), received the first dose combined with phacoemulsification followed by the other two injections, one and two months postoperatively. Group (II), received the first dose two weeks before phacoemulsification followed by the other two injections, one and two months from the first one. Results The baseline mean central macular thickness (CMT) was comparable in both groups (P&gt;0.05); however, the CMT one month after the third injection was 261±36 µm for Group (II) vs 320±65 µm for Group (I), which was statistically significant (P&lt;0.001). Both study groups were comparable regarding the baseline mean best corrected visual acuity (BCVA) (P&gt;0.05); however, the mean BCVA at the end of follow-up was 0.32±0.23 LogMAR for Group (II) vs 0.50±0.19 LogMAR for Group (I), which was statistically significant (P&lt;0.001). Conclusion Intravitreal RBZ injection has a significant clinical improving effect on both CMT and BCVA in diabetic patients with diabetic macular edema (DME) undergoing phacoemulsification; although, it is preferred to inject a single intravitreal injection two weeks before phacoemulsification to reach its peak effect in counteracting the high levels of VEGF released during the surgery.

Validity of focal laser photocoagulation followed by a single intravitreal ranibizumab injection for retinal artery macroaneurysm

Background To evaluate safety and efficacy of dual focal laser (DFL) followed by a single intravitreal ranibizumab injection for exudative retinal artery macroaneurysms (RAM). Methods Retrospective review of records of eyes with RAM; treated between February 2012 and November 2020; was done, to collect and analyze the following data: Treatment details, features of RAM, associated retinal disease, best-corrected visual acuity (BCVA), central macular thickness (CMT), signs of RAM involution, and possible complications. We enrolled cases that had been treated by Direct and perilesional focal laser, followed by a single intravitreal ranibizumab injection a few days later, and had been followed-up for at least 6 months. Outcome measures included: change in BCVA, change in CMT, and complications. Results 14 patients were enrolled. All cases were isolated RAM (without other retinal disease) with macular edema±hard exudates (100%). 12 cases (85.7%) were exudative, and 2 cases (14.3%) also had a hemorrhagic component (mixed type). Hemorrhagic macroaneurysms without exudation were not included in the study. RAM was fusiform in 12 cases (85.7%) and saccular in 2 cases (14.3%). RAM involved the upper temporal arcade in 10 cases (71.4%) and the lower temporal arcade in 4 cases (28.6%). RAM involved second order arteries in 10 cases (71.4%) and third order arteries in 4 cases (28.6%). Logarithm of the minimum angle of resolution (LogMAR) BCVA improved from an initial 0.71±0.35 to 0.27±0.26 at final follow-up. CMT was reduced from 417±82 μ to 285±31 μ at final follow-up. The mean interval between laser and ranibizumab injection was 3.2±2.9 days. The mean follow-up duration was 8.0±2.6 months. Involution/thrombosis- fibrosis of RAM was induced in all cases (100%). Conclusion Combined dual focal laser coagulation and single intravitreal ranibizumab injection for RAM are safe and effective, and may eliminate the need for repeated intravitreal injections. Isolated exudative macroaneurysms may be suitable for this combined approach.

Population Pharmacokinetics of Ranibizumab Delivered via the Port Delivery System Implanted in the Eye in Patients with Neovascular Age-Related Macular Degeneration.

The port delivery system with ranibizumab (PDS) is designed to continuously deliver ranibizumab to maintain therapeutic drug concentrations in the vitreous of the eye for an extended duration. The PDS has been evaluated for the treatment of neovascular age-related macular degeneration in the Ladder (PDS 10, 40, and 100mg/mL, with refill exchanges as needed, versus monthly intravitreal ranibizumab 0.5mg), Archway (PDS 100mg/mL with 24-week refill exchanges, versus monthly intravitreal ranibizumab 0.5mg), and ongoing Portal (PDS 100mg/mL with 24-week refill exchanges) clinical trials. Data from Ladder, Archway, and Portal were used to develop a population pharmacokinetics (PK) model to estimate the ranibizumab release rate from the PDS implant, describe ranibizumab PK in serum and aqueous humor, and predict the concentration in vitreous humor. A model was developed to adequately describe the serum and aqueous humor PK data, as suggested by goodness-of-fit plots as well as visual predictive checks. In the final model, the first-order implant release rate was estimated to be 0.00654 (1/day), corresponding to a half-life of 106days, consistent with the implant release rate determined invitro. The model-predicted vitreous concentrations achieved with PDS 100mg/mL given every 24weeks were below the intravitreal peak concentration and above the intravitreal trough concentration of ranibizumab over the entire 24-week refill interval. The results demonstrate a durable release of ranibizumab from the PDS with a half-life of 106days, providing vitreous exposure to ranibizumab for at least 24weeks that is within the range of exposure for monthly intravitreal treatment.

Ten-year visual outcome and change in chorioretinal atrophy after intravitreal ranibizumab for macular neovascularization in pathologic myopia.

To investigate the 10-year visual outcome and chorioretinal atrophy after a single intravitreal ranibizumab injection (IVR) followed by a pro re nata (PRN) regimen for myopic macular neovascularization (mMNV) in pathologic myopia, and to identify the factors associated with 10-year best-corrected visual acuity (BCVA). This retrospective observational study evaluated 26 consecutive treatment-naïve eyes (26 patients) with mMNV in pathologic myopia who underwent a single IVR followed by a PRN regimen of IVR and/or intravitreal aflibercept injection and observed over 10 years. We assessed changes in BCVA and morphological parameters, including the META-PM Study category as a chorioretinal atrophy index. The logarithm of the minimum angle of resolution BCVA changed from 0.36 (Snellen, 20/45) ± 0.39 to 0.39 (20/49) ± 0.36 over 10 years of observation. Compared to baseline, 1-year BCVA improved (P = 0.002), whereas 2-10-year BCVA was not significantly different. Total injection frequency was 3.8 ± 2.6. In none of the eyes, 10-year BCVA was 20/200 or less. Ten-year BCVA correlated with baseline BCVA (P = 0.01, r = 0.47). The META-PM Study category progressed in 60% of eyes. There were no drug-induced complications. BCVA in eyes with mMNV in pathologic myopia was maintained for 10 years after a single IVR followed by a PRN regimen without drug-induced complications. The META-PM Study category progressed in 60% of eyes, especially those with older baseline age. Early diagnosis and treatment of mMNV are essential to maintain good long-term BCVA.

Analysis of ocular fluid in patients with ranibizumab-recalcitrant neovascular age-related macular degeneration who have serum anti-ranibizumab antibodies.

To evaluate whether anti-drug antibodies (ADAs) are present in the ocular fluid of patients with ranibizumab-recalcitrant neovascular age-related macular degeneration (nAMD). Two serum ADA-positive ranibizumab-recalcitrant patients and two serum ADA-negative controls were recruited from patients with nAMD treated with ranibizumab monotherapy. Recalcitrance was defined as persistent fluid after ≥6 monthly ranibizumab injections. Serum and aqueous humor ADAs were detected by enzyme-linked immunosorbent assay and immunoprecipitation, respectively. Two of 156 ranibizumab-treated patients were ADA-positive. The patients received six and 14 ranibizumab injections, respectively, up to 4 weeks prior to blood collection. The serum ADA concentration was estimated to be approximately 50,000 ng/mL. Neutralizing ADAs were confirmed in both samples. A specific band was detected by immunoprecipitation only in ADA-positive samples, consistent with the results of enzyme-linked immunosorbent assay. Based on an assessment of the degree of sensitivity of commercially available anti-ranibizumab antibodies, it was estimated that the immunoprecipitation method could detect ADA levels >30 ng. Nevertheless, ADAs were not detected in the aqueous humor of either the experimental or control group. In the aqueous humor, ADAs are either not present or are present at a lower concentration than that which can be detected by immunoprecipitation. This presumably reflects the fact that blood ADA is the product of systemic circulation clearance through anterior elimination of intravitreal ranibizumab. Based on our results, ADAs do not return to the eye in sufficient quantities to interfere with the action of ranibizumab in the vitreous cavity.

Faricimab Effectively Resolves Intraretinal Fluid and Preserves Vision in Refractory, Recalcitrant, and Nonresponsive Neovascular Age-Related Macular Degeneration.

To evaluate the functional and anatomic outcomes of faricimab treatment in patients with neovascular age-related macular degeneration (nAMD) who are unresponsive to other anti-vascular endothelial growth factor (VEGF) therapies. A retrospective interventional study was conducted on patients with refractory nAMD who were initially treated with intravitreal bevacizumab, ranibizumab, or aflibercept. These patients were switched to monthly faricimab injections. The central subfield thickness (CST), intraretinal fluid (IRF)or subretinal fluid (SRF) height, and visual acuities were compared before and after faricimab treatment. A total of 13 eyes (eight right eyes and five left eyes) from 11 patients were followed for 10.4 ± 6.9 months after bevacizumab treatment and 40.3 ± 28.7 months after aflibercept treatment before switching to faricimab. The follow-up time for patients receiving a mean number of 3.7 ± 1.3 faricimab injections was 3.4 ± 1.2 months. The overall median CST was reduced by 18µm (p=0.001) from 342µm to 318µm, along with a reduction of 89µm (p=0.03) in IRF/SRF height from 97µm to 40µm. Following three consecutive injections, the CST showed a significant reduction of 21.5µm (p=0.004) from 344µm to 322.5µm, and IRF/SRF height was reduced by 89µm (p=0.03) from 104µm to 18.5µm. The intraretinal fluid size decreased and leakage stopped, as seen on fluorescein angiography. Visual acuity remained stable after switching to faricimab treatment (0.59 ± 0.45 logMAR vs 0.58 ± 0.45 logMAR, p=1). Faricimab has proven to be an effective treatment for nAMD patients resistant to other anti-VEGF agents. It demonstrates significant anatomical improvement and vision preservation in this challenging patient population.

CO35 Real-World Effectiveness of Intravitreal Ranibizumab and Aflibercept for Eyes with Central Retinal Vein Occlusion: A Multi-Institutional Cohort Study in Taiwan

Intravitreal ranibizumab and aflibercept is the mainstream therapy for central retinal vein occlusion (CRVO), a common cause of vision loss in adults. However, the long-term effectiveness of changes in central retinal thickness (CRT) and visual acuity (VA) post ranibizumab and aflibercept therapy remains unclear in Taiwan.

Effects of Intravitreal Ranibizumab Injection on Peripheral Retinal Microcirculation and Cytokines in Branch Retinal Vein Occlusion with Macular Edema.

Background and Objectives: To investigate peripheral blood flow in retinal vessels and vessel diameters after intravitreal ranibizumab injection (IRI) and the relationship between these parameters and cytokines in branch retinal vein occlusion (BRVO) with macular edema. Materials and Methods: We assessed relative flow volume (RFV) and the width of the main and branch retinal arteries and veins in the occluded and non-occluded regions before and after IRI in 37 patients with BRVO and macular edema. Measurements were made using laser speckle flowgraphy (LSFG). When performing IRI, we obtained samples of aqueous humor and analyzed them using the suspension array method to evaluate vascular endothelial growth factor (VEGF), placental growth factor (PlGF), platelet-derived growth factor (PDGF)-AA, soluble intercellular adhesion molecule (sICAM)-1, monocyte chemoattractant protein 1 (MCP-1), interleukin (IL)-6, IL-8, and interferon-inducible 10-kDa protein (IP-10). Results: In both retinal regions, before and after IRI, the RFV in the main artery and vein showed a significant correlation with the summed RFV in the respective branch vessels 1 and 2. In the occluded region, the RFV in the main vein was significantly negatively correlated with MCP-1, PDGF-AA, IL-6, and IL-8; the RFV in branch vein 1 was significantly negatively correlated with PlGF, MCP-1, IL-6, and IL-8; PDGF-AA was significantly negatively correlated with the width of the main and branch veins; and the RFVs of the main artery and vein decreased significantly from before to 1 month after IRI. Conclusions: Contrary to expectations, the study found that anti-VEGF therapy does not affect RFV in arteries and veins in patients with BRVO and macular edema. Furthermore, retinal blood flow is poor in patients with high MCP-1, IL-6, and IL-8. Finally, high PDGF-AA may result in smaller venous diameters and reduced retinal blood flow.

Risk analysis for patients with arterial thromboembolic events after intravitreal ranibizumab or aflibercept injections

Intravitreal anti–vascular endothelial growth factor (anti-VEGF) agents have been increasingly applied in the treatment of retinal neovascular diseases. Concerns have arisen that these intravitreal agents may be associated with a potential risk of arterial thromboembolic (ATE) events. We conducted a retrospective, nationwide population‐based cohort study to analyze the risks for ATE events in patients receiving intravitreal ranibizumab (IVR) or intravitreal aflibercept (IVA). Data (2011–2018) were obtained from Taiwan’s National Health Insurance Research Database. Cox proportional-hazards model was used to identify the risk factors for ATEs. Of the total 3,469 patients, 1393 and 2076 patients received IVR and IVA, respectively. In our result, 38 ATEs occurred within 6 months after IVR or IVA. The risk of ATEs was lower in patients receiving IVR than in those receiving IVA (adjusted hazard ratio [aHR], 0.27; 95% confidence interval [CI], 0.11–0.66). Patients with coronary artery disease (CAD) exhibited a higher risk of ATEs than did those without CAD (aHR, 3.47; 95% CI, 1.41–8.53). The risk of ATEs was higher in patients with an event of acute myocardial infarction (AMI) or ischemic stroke (IS) within 6 months prior to index IVI than in those without recent AMI/IS events (aHR, 23.8; 95% CI, 7.35–77.2 and IS: aHR, 290.2; 95% CI, 103.1–816.4). In conclusion, compared with IVA, IVR was associated with a lower risk of ATEs. When strategies for anti-VEGF agents are devised, risk factors, such as CAD and a history of AMI or IS within 6 months should be considered. Further large-scale studies are warranted to elucidate the safety of anti-VEGF injections.

Evaluation of marker-based optical coherence tomography findings in diabetic macular edema treated with intravitreal ranibizumab therapy

To evaluate the short-term effects of intravitreal ranibizumab (IVR) injection on visual and structural changes in diabetic macular edema (DME). A retrospective study including 108 eyes of 74 patients with DME in which IVR injection was conducted three times at one-month intervals. Retinal and choroidal layers, as well as the subretinal fluid area, were measured at baseline and during 3 months of treatment. The correlation between structural changes and visual acuity was investigated. In general, most of the retinal layers tended to decrease after treatment. Resolution of subretinal fluid remained relatively superior in predicting the outcome of ranibizumab injection. In addition, we found that reduction of photoreceptor layer (PRL) thickness provided the best estimation of visual acuity gain. Neural recovery in PRL is associated with better visual improvement. Individual retinal segmentation would be beneficial for monitoring and evaluating ranibizumab treatment in DME. Evaluar los efectos a corto plazo de la inyección intravítrea de ranibizumab (IVR) sobre los cambios visuales y estructurales en el edema macular diabético. Pacientes y métodos: Estudio retrospectivo que incluyó 108 ojos de 74 pacientes con edema macular diabético en los que se inyectó tres veces IVR 3 veces con intervalos de un mes. Las capas retinal y coroidea, así como el área de líquido subretiniano, se midieron al inicio del estudio y durante 3 meses de tratamiento. Se investigó la correlación entre los cambios estructurales y la agudeza visual. En general, la mayoría de las capas de la retina tendieron a disminuir después del tratamiento. La resolución del líquido subretiniano siguió siendo relativamente superior para predecir el resultado de la inyección de ranibizumab. Además, encontramos que la reducción del grosor de la capa de fotorreceptores tuvo la mejor estimación de la ganancia de agudeza visual. La recuperación neural de de la capa de fotorreceptores se asocia con una mejor mejora visual. La segmentación individual de la retina sería beneficiosa para monitorear y evaluar el tratamiento con ranibizumab en el edema macular diabético.