Anti-vascular Endothelial Growth Factor Agents Research Articles

Short-term intraocular pressure changes after intravitreal aflibercept 2 mg, aflibercept 8 mg and faricimab: a prospective, comparative study

Background/aimsIntravitreal injection (IVT) of anti-vascular endothelial growth factor agents is the standard of care for several retinal diseases but can cause intraocular pressure (IOP) elevations. This study investigates short-term postinjection...

First-year real-world experience of intravitreal brolucizumab injection for refractory neovascular age-related macular degeneration.

To investigate the first-year real-world anatomical and functional outcomes of intravitreal brolucizumab injection in eyes with refractory neovascular age-related macular degeneration (nAMD). Retrospective observational study. nAMD patients who showed poor response to previous anti-vascular endothelial growth factor (VEGF) agents were switched to brolucizumab. Functional and anatomical outcomes were evaluated at initial treatment of nAMD, after treatment with other anti-VEGF agents and after switching and treating with brolucizumab for 1 year. Safety profile was also evaluated after brolucizumab injection. Best-corrected visual acuity (BCVA), central foveal thickness (CFT), subfoveal choroidal thickness (SFCT), and the presence of fluid in different compartments (intraretinal fluid [IRF], subretinal fluid [SRF], pigment epithelial detachment [PED]) were assessed at each time point. A total of 40 eyes of 40 patients were included in the study. BCVA remained unchanged throughout treatment (p > 0.05). CFT did not change after treatment with other anti-VEGF agents (p = 0.588) but decreased after switching to brolucizumab (p < 0.001). SFCT decreased after treatment with other anti-VEGF agents (p = 0.025) but not after switching to brolucizumab (p = 0.236). Presence of SRF (p = 0.001) and PED (p = 0.001) decreased significantly after switching to brolucizumab, despite their persistence with prior treatments using other anti-VEGF agents. However, IRF persisted even after switching to brolucizumab (p = 0.745). Intraocular inflammation (IOI)-related adverse events were reported in 3 eyes (7.14%). Analysis of first-year real-world outcomes after switching to brolucizumab in nAMD patients refractory to other anti-VEGF agents showed improved anatomic outcomes, limited functional improvement and low incidence of IOI-related adverse events.

Term infant brain MRI after ROP treatment by anti-VEGF injection versus laser therapy.

Intravitreal injection of anti-vascular endothelial growth factor (anti-VEGF) agents is used to treat posterior type 1 retinopathy of prematurity (ROP). Recent reports indicate that anti-VEGF therapy may be associated with white matter brain injury, according to animal studies, and neurodevelopmental impairments in children born preterm. We investigated whether type 1 ROP treated with bevacizumab is associated with structural brain injury on infant term magnetic resonance images (MRIs) in very low birth weight infants compared with those treated with laser ablation. We retrospectively reviewed the medical records of very low birth weight infants from 2006 to 2021 with type 1 ROP who had been treated with laser or anti-VEGF therapy. Intravitreal bevacizumab injection was used for type 1 ROP in zone 1 or very posterior zone 2 or when laser treatment was not feasible. A pediatric neuroradiologist reviewed brain MRIs at term equivalent age (36-46 weeks' postmenstrual age) and classified infants for severity (no/mild vs moderate/severe) of overall brain and white matter injury using the validated Kidokoro scoring system. Fifty-two infants met inclusion criteria: 35 (67%) treated with laser and 17 (33%) with bevacizumab. Moderate-to-severe brain injury scores were not statistically different between bevacizumab and laser treatment groups in either continuous or binary adjusted analyses, for either the overall score or the white matter subscore. Severity of structural injury on term brain MRI (total and white matter) did not differ between infants with type 1 ROP treated with anti-VEGF agent (bevacizumab) and those treated with laser ablation.

Occlusive retinal vasculitis and scleritis following brolucizumab treatment: A case report.

Brolucizumab is an anti-vascular endothelial growth factor agent. Clinical trials have demonstrated excellent efficacy of brolucizumab for neovascular age-related macular degeneration in terms of both visual and anatomic outcomes. However, compared with conventional anti-vascular endothelial growth factor therapy, this new treatment has a higher incidence of complications, particularly the development of occlusive retinal vasculitis. In this case report, we describe a patient who developed occlusive retinal vasculitis following brolucizumab treatment for age-related macular degeneration, followed by scleritis 141 days later. A 67-year-old Japanese man with a diagnosis of polypoidal choroidal vasculopathy in his right eye has received 18 intravitreal injections of aflibercept in the past 4 years. Because of a decline in treatment efficacy, intravitreal brolucizumab injection (IVBr) was initiated. However, 17 days after the second IVBr, the patient developed extensive occlusive retinal vasculitis with intraocular inflammation. Occlusive retinal vasculitis in the right eye was diagnosed as a complication of brolucizumab therapy. Corticosteroid treatment was initiated. The occlusive retinal vasculitis resolved 121 days after the second IVBr, and corticosteroid treatment was discontinued on day 138. However, on day 158 after the second IVBr, scleritis with intraocular inflammation developed. By day 184 after the second IVBr, both the scleritis and intraocular inflammation had resolved with the resumption of topical corticosteroid treatment. This case underscores the potential for brolucizumab-induced scleritis and emphasizes the importance of recognizing and promptly managing this complication. Furthermore, it highlights the need for long-term careful follow-up in patients who develop occlusive retinal vasculitis after brolucizumab treatment.

Serial intravitreal injections in age-related macular degeneration patients from the dry eye disease perspective: a cross-sectional study

BackgroundTo evaluate the effects of serial intravitreal injections (IVI) on the ocular surface and meibomian glands in patients with neovascular age-related macular degeneration (nAMD).MethodsPatients receiving anti-vascular endothelial growth factor (anti-VEGF) agent injections for unilateral nAMD were included. Untreated fellow eyes served as the control group. All participants followed a pre-IVI asepsis protocol with povidone-iodine (PI). Ocular surface diseases index (OSDI) questionnaire scores, first and average non-invasive tear break-up time (fNITBUT and avgNITBUT), Schirmer-1 test results, corneal staining score (according to Oxford scale), meibomian gland (MG) loss rates of lower and upper eyelids were recorded four weeks after the last IVI.ResultsForty-two nAMD patients with a mean age of 63.3 ± 19.4 were included in the study. The mean OSDI score was 20.3 and the median of IVI number was 9 (6–22). There were no statistically significant difference between treated and untreated fellow eyes regarding fNITBUT (5.6 vs. 4.5, p = 0.872), avgNITBUT (6.2 vs. 7.2, p = 0.968), Shirmer-1 results (7 vs. 7, p = 0.854), corneal staining (0.3 vs. 0.2, p = 0.341), lower and upper MG loss rate (29.3 vs. 28.4, p = 0.162, and 27.1 vs. 26.9, p = 0.476, respectively). Only significant correlation was observed between age with lower and upper MG loss rate (r:0.396, p = 0.042, and r:0.365, p = 0.047).ConclusionThe results of the present study demonstrated that serial IVI of anti-VEGF agents with PI asepsis is well tolerated by nAMD patients in terms of ocular surface, MG loss and DED measurements.

Patient-Centered Economic Burden of Diabetic Macular Edema: Retrospective Cohort Study.

Diabetic macular edema (DME), a leading cause of blindness, requires treatment with costly drugs, such as anti-vascular endothelial growth factor (VEGF) agents. The prolonged use of these effective but expensive drugs results in an incremental economic burden for patients with DME compared with those with diabetes mellitus (DM) without DME. However, there are no studies on the long-term patient-centered economic burden of DME after reimbursement for anti-VEGFs. This retrospective cohort study aims to estimate the 3-year patient-centered economic burden of DME compared with DM without DME, using the Common Data Model. We used medical data from 1,903,603 patients (2003-2020), transformed and validated using the Observational Medical Outcomes Partnership Common Data Model from Seoul National University Bundang Hospital. We defined the group with DME as patients aged >18 years with nonproliferative diabetic retinopathy and intravitreal anti-VEGF or steroid prescriptions. As control, we defined the group with DM without DME as patients aged >18 years with DM or diabetic retinopathy without intravitreal anti-VEGF or steroid prescriptions. Propensity score matching, performed using a regularized logistic regression with a Laplace prior, addressed selection bias. We estimated direct medical costs over 3 years categorized into total costs, reimbursement costs, nonreimbursement costs, out-of-pocket costs, and costs covered by insurance, as well as healthcare resource utilization. An exponential conditional model and a count model estimated unbiased incremental patient-centered economic burden using generalized linear models and a zero-inflation model. In a cohort of 454 patients with DME matched with 1640 patients with DM, the economic burden of DME was significantly higher than that of DM, with total costs over 3 years being 2.09 (95% CI 1.78-2.47) times higher. Reimbursement costs were 1.89 (95% CI 1.57-2.28) times higher in the group with DME than with the group with DM, while nonreimbursement costs were 2.54 (95% CI 2.12-3.06) times higher. Out-of-pocket costs and costs covered by insurance were also higher by a factor of 2.11 (95% CI 1.58-2.59) and a factor of 2.01 (95% CI 1.85-2.42), respectively. Patients with DME had a significantly higher number of outpatient (1.87-fold) and inpatient (1.99-fold) visits compared with those with DM (P<.001 in all cases). Patients with DME experience a heightened economic burden compared with diabetic patients without DME. The substantial and enduring economic impact observed in real-world settings underscores the need to alleviate patients' burden through preventive measures, effective management, appropriate reimbursement policies, and the development of innovative treatments. Strategies to mitigate the economic impact of DME should include proactive approaches such as expanding anti-VEGF reimbursement criteria, approving and reimbursing cost-effective drugs such as bevacizumab, advocating for proactive eye examinations, and embracing early diagnosis by ophthalmologists facilitated by cutting-edge methodologies such as artificial intelligence for patients with DM.

A Brief Review on Adult-Onset Coats' Disease.

Adult-onset Coats disease is an uncommon and vision-threatening disease characterized by the development of abnormal blood vessels in the retina. Coats' disease commonly affects children in the first decade of life, but very rarely manifests in adults after the third decade of life, or who characteristically present with unilateral vision loss. Despite being a sight-threatening disease, the etiology remains inconclusive and various genetic and vascular abnormalities are implicated. Diagnosis relies on ophthalmologic examination, fundus photography, fluorescein angiography, and optical coherence tomography. Treatment modalities include laser photocoagulation, intravitreal injections of anti-vascular endothelial growth factor agents, and, in advanced cases, surgical interventions are needed and the treatment is aimed at avoiding complications like retinal detachment and neovascular glaucoma, which were comparatively rare in adult-onset Coats' disease. Despite therapeutic advancements, the prognosis varies, with some patients experiencing significant visual impairment. This review outlines the clinical features, diagnosis, management, and prognosis of adult-onset Coats' disease, underscoring the importance of early detection and intervention in optimizing visual outcomes.

Bruton's tyrosine kinase inhibition suppresses pathological retinal angiogenesis.

Pathological retinal angiogenesis is a typical manifestation of vision-threatening ocular diseases. Many patients exhibit poor response or resistance to anti-vascular endothelial growth factor (VEGF) agents. Bruton's tyrosine kinase (BTK) controls the proliferation and function of immune cells. Therefore, we examined the anti-inflammatory and anti-angiogenic effects of BTK inhibition on retinal angiogenesis. Retinal neovascularisation and vascular leakage in oxygen-induced retinopathy in C57/BL6J mice were assessed by whole-mount retinal immunofluorescence. PLX5622 was used to deplete microglia and Rag1-knockout mice were used to test the contribution of lymphocytes to the effects of BTK inhibition. The cytokines, activation markers, inflammatory and immune-regulatory activities of retinal microglia/macrophages were detected using qRT-PCR and immunofluorescence. NLRP3 was detected by western blotting, and the effects of BTK inhibition on the co-culture of microglia and human retinal microvascular endothelial cells (HRMECs) were examined. BTK inhibition suppressed pathological angiogenesis and vascular leakage, and significantly reduced retinal inflammation, which involved microglia/macrophages but not lymphocytes. BTK inhibition increased anti-inflammatory factors and reduced pro-inflammatory cytokines that resulted from NLRP3 inflammasome activation. BTK inhibition suppressed the inflammatory activity of microglia/macrophages, and acted synergistically with anti-VEGF without retinal toxicity. Moreover, the supernatant of microglia incubated with BTK-inhibitor reduced the proliferation, tube formation and sprouting of HRMECs. BTK inhibition suppressed retinal neovascularisation and vascular leakage by modulating the inflammatory activity of microglia and macrophages. Our study suggests BTK inhibition as a novel and promising approach for alleviating pathological retinal angiogenesis.

Outcomes After Switching to Faricimab for Refractive Macular Edema in Treatment-Experienced Eyes with Neovascular Age-Related Macular Degeneration.

To examine response to faricimab in neovascular age-related macular degeneration (nARMD) refractory to traditional anti-vascular endothelial growth factor (anti-VEGF) agents. Retrospective chart review was conducted on eyes with nARMD with persistent subretinal and/or intraretinal fluid despite previously receiving ≥15 injections with ≥2 different anti-VEGF agents. Best corrected visual acuity (BCVA) and optical coherence tomography (OCT) parameters were collected at baseline, initial post-injection visit, and most recent visit with OCT following last faricimab. Nineteen eyes were included. Average logMAR BCVA was 0.47 ± 0.60 at baseline, 0.42 ± 0.47 at initial follow-up (p=0.38), and 0.51 ± 0.63 at final visit (p = 0.50). Average central subfield thickness (CST) was 310 ± 92μm at baseline, 279 ± 88μm at initial follow-up (p = 0.001), and 274 ± 100μm at last visit (p < 0.001). 9 eyes (47%) achieved resolution of fluid at both initial and final follow-up visits. Faricimab mildly decreased CST and reduced fluid in some nARMD eyes refractory to traditional anti-VEGF agents but had minimal effect on BCVA.

Intravitreal Dexamethasone Implant in Anti-Vascular Endothelial Growth Factor Pretreated Diabetic Macular Edema-A Swiss Cohort Study.

Diabetic macular edema (DME) is a significant cause of visual impairment, often treated with anti-vascular endothelial growth factor (anti-VEGF) agents. However, some patients do not respond adequately to this treatment. This study aims to evaluate the contribution of the intravitreal dexamethasone (DEX) implant as a second-line treatment in DME patients with insufficient response to anti-VEGF therapy or with high treatment burden. This retrospective multicenter cohort study was conducted across seven clinical sites in Switzerland. The study included eyes with active DME that had been pretreated with anti-VEGF for at least six months before receiving DEX therapy. Data were extracted from electronic patient records, focusing on best-corrected visual acuity (BCVA), central subfield thickness (CST), and injection frequency. A total of 95 eyes from 89 patients (38.8% females, mean age 65.6 ± 9.1 years, follow-up time 80.6 ± 38.5 [13.5-166.7] months) were analyzed. Prior to the first DEX implant, eyes had undergone an average of 16.0 ± 13.3 anti-VEGF injections over 32.5 ± 22.4 months. Post-DEX treatment, 22.1% of eyes received DEX monotherapy, 44.2% received a combination of DEX and anti-VEGF, 25.3% continued with anti-VEGF monotherapy, and 8.4% received no further treatment. The number of anti-VEGF injections decreased significantly from 6.4 ± 3.1 in the year before DEX to 1.6 ± 2.4 in the year after DEX (p < 0.001). BCVA remained stable (0.4 ± 0.3 logMAR at baseline, 0.4 ± 0.5 logMAR at 24 months, p = 0.2), while CST improved from 477.7 ± 141.0 to 320.4 ± 125.5 μm (p < 0.001), and the presence of retinal fluid decreased from 98.0% to 61.1% (p = 0.021). During follow-up, 26.3% of eyes required glaucoma medication, 4.2% underwent glaucoma surgery, and 1.1% needed cataract surgery. In real-world clinical settings, the addition of DEX to anti-VEGF therapy in DME patients significantly reduces treatment burden and retinal fluid while maintaining visual function. Treatment decisions should balance anatomical and functional outcomes, considering individual patient needs.

A Nanogel Formulation of Anti-VEGF Peptide for Ocular Neovascularization Treatment.

Age-related macular degeneration (AMD) is an eye disorder that can lead to visual impairment in elder patients, and current treatments include repeated injections of monoclonal antibody-based antivascular endothelial growth factor (anti-VEGF) agents. This study investigates the potential of a nanoformulation of a peptide anti-VEGF molecule for neovascular AMD. Anti-VEGF peptide HRHTKQRHTALH (HRH), which has high affinity to VEGF-Fc receptor, was used as the bioactive agent to control neovascularization of the retina. The nanoformulation consisting of hyaluronic acid nanogel was generated by incorporating divinyl sulfone and cholesterol to increase the stability and control the size of the nanodrug. The encapsulation efficacy of nanogel was 65%, and drug release was 34.72% at the end of 192 h. Obtained nanogels were efficiently internalized in 15 min by human umbilical vascular endothelial cells (HUVECs) and ARPE-19 cells, and results indicate that nanoformulation is not toxic to ARPE-19 cells, whereas it inhibits HUVEC proliferation owing to anti-VEGF peptide in the nanogel structure. In the coculture experiment in which retinal penetration was modeled, it was observed that the nanogel reached HUVECs and negatively affected their proliferation without disturbing the monolayer of ARPE-19 cells. In vivo experiments with chick chorioallantoic membrane revealed that nanogel formulation has higher antiangiogenesis activity compared to free HRH. Additionally, in an oxygen-induced retinopathy model, the excessive growth of blood vessels was notably suppressed in mice treated with HRH-loaded nanogel. This research indicates that nanogels formulated in this study are promising candidates as a topical treatment for AMD.

Can Cytoreductive Nephrectomy Improve Outcomes of Nivolumab Treatment in Patients with Metastatic Clear-Cell Renal Carcinoma?

Background: This study aimed to investigate the effect of cytoreductive nephrectomy (CN) on the survival outcomes of nivolumab used as a subsequent therapy after the failure of at least one anti-vascular endothelial growth factor (VEGF) agent in patients with metastatic clear-cell renal-cell carcinoma (ccRCC). Methods: We included 106 de novo metastatic ccRCC patients who received nivolumab after progression on at least one anti-VEGF agent. Multivariate Cox regression analysis was performed to investigate the factors affecting survival in patients receiving nivolumab. Results: Of the 106 de novo metastatic ccRCC patients, 83 (78.3%) underwent CN. There were no statistical differences between the two groups in terms of age, gender, Eastern Cooperative Oncology Group (ECOG) score, tumor size, International Metastatic RCC Database Consortium (IMDC) risk group, number of previous treatment lines, first-line anti-VEGF therapy, or metastasis sites (p = 0.137, p = 0.608, p = 0.100, p = 0.376, p = 0.185, p = 0.776, p = 0.350, and p = 0.608, respectively). The patients who received nivolumab with CN had a longer time to treatment discontinuation (TTD) [14.5 months, 95% confidence interval (CI): 8.6-20.3] than did those without CN 6.7 months (95% CI: 3.9-9.5) (p = 0.001). The median overall survival (OS) was 22.7 months (95% CI: 16.1-29.4). The patients with CN had a median OS of 22.9 months (95% CI: 16.3-29.4), while those without CN had a median OS of 8.1 months (95% CI: 5.6-10.5) (p = 0.104). In the multivariate analysis, CN [hazard ratio (HR): 0.521; 95% CI: 0.297-0.916; p = 0.024] and the IMDC risk score (p = 0.011) were statistically significant factors affecting TTD; however, the IMDC risk score (p = 0.006) was the only significant factor for overall survival. Conclusions: Our study showed that the TTD of nivolumab was longer in metastatic ccRCC patients who underwent cytoreductive nephrectomy.

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

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. 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. 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 (40.3-57.9s) versus vials (ranibizumab, 62.8-98.0s; aflibercept, 71.9-79.5s), 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. 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.

High-Dose Brolucizumab for Refractory Neovascular Age-Related Macular Degeneration Resistant to Standard-Dose Brolucizumab.

The aim of this study was to evaluate the efficacy and safety of escalating the dosage of intravitreal brolucizumab in patients with refractory neovascular age-related macular degeneration (AMD). This retrospective study included 17 eyes of 17 patients with refractory AMD treated with high-dose brolucizumab (12mg/0.1ml) for over 12months. Patients initially received at least one anti-vascular endothelial growth factor (anti-VEGF) agent and were switched to standard-dose brolucizumab (6mg/0.05ml). Those who showed a suboptimal response to standard-dose treatment had their dosage of brolucizumab escalated. Visual acuity was maintained from 68.3 ± 3.4 letters to 70.7 ± 3.2 letters after 12months of high-dose treatment (P = 0.128). Central subfield thickness was 343.7 ± 17.0μm before high-dose treatment and 316.7 ± 18.5μm at 12months (P = 0.083). The proportions of patients with subretinal fluid and serous pigment epithelial detachment significantly decreased from 82.4% to 41.2% and from 52.9% to 17.6%, respectively, after high-dose treatment (P = 0.039 and P = 0.031, respectively). The treatment interval extended from 7.2 ± 2.4weeks to 10.2 ± 2.2weeks after switching to standard-dose brolucizumab (P < 0.001) and was maintained at 13.5 ± 2.8weeks after increasing the dose (P = 0.154). No severe ocular adverse events were observed. High-dose brolucizumab was effective in patients who did not respond to standard-dose brolucizumab after switching from previous anti-VEGF agents. Increasing the dosage could offer sustained disease control and reduce the treatment burden for patients with refractory AMD.

Association of microaneurysms with retinal vascular alterations in patients with retinal vein occlusion

ObjectiveTo investigate the localization, distribution, and type of central microaneurysms (MAs) and their relationship with retinal vascular alterations in patients with retinal vein occlusion (RVO). MethodsIn this cross-sectional study, ultra-widefield color fundus photography (UWF-CF), standard and single-capture 65° widefield (WF) optical coherence tomography angiography (OCTA) were performed in consecutive patients with RVO treated at the Department of Ophthalmology and Optometry, Medical University of Vienna. UWF-CF, en face and B-Scans in 6 mm × 6 mm OCTA were examined for detection of MAs. Nonperfusion areas (NPA) and collateral vessels (CV) were evaluated on WF-OCTA, ghost vessels (GV), and tortuous vessels (TV) on UWF-CF. ResultsOne-hundred-and-twelve patients were included in the study, and data from 59 eyes of 59 patients with disease duration longer than 3 months, good image quality, and without relevant ocular comorbidities were eligible for statistical analysis. Fifty-six of 59 (94.9%) patients were previously treated with anti-vascular endothelial growth factor agents for macular edema, 31 of 59 (52.5%) patients presented with MAs in the central 6 mm and 60 MAs were found in total using multimodal imaging. There was no statistically significant difference in the greatest diameter of fluid-associated versus non-fluid-associated MAs (p = 0.53). Eyes with MAs were associated with CV, TV, and GV (χ2-test; p < 0.001, p = 0.0498, and p = 0.001). Median NPA was 27.3 mm2 (quartiles 1.3–62.8 mm2) in eyes with MAs and 0 mm2 (quartiles 0–36.2 mm2) in eyes without MAs (Mann-Whitney-U-test; p = 0.018). ConclusionMAs were associated with extensive NPA, the presence of CV, GV, and TV. There was no correlation between the diameter of the MA and the adjacent intraretinal fluid in our predominantly pretreated RVO study patients.

Systemic effects of anti-VEGF intravitreal injection in patients with age-related macular degeneration: A multi-institutional real-world study.

In individuals aged >50 years, age-related macular degeneration (AMD) is the leading cause of irreversible blindness. Intravitreal injections of antivascular endothelial growth factor (VEGF) agents (bevacizumab, ranibizumab, and aflibercept) show good efficacy and similar incidences of systemic adverse events (SAEs). However, comparative studies between agents are limited. Our study aimed to compare the real-world SAE risks of bevacizumab, ranibizumab, and aflibercept users. This retrospective cohort study identified new bevacizumab, ranibizumab, and aflibercept users in a multi-institutional database in Taiwan between 2014 and 2019. Inverse probability of treatment weights (IPTW) with propensity scores was conducted to achieve homogeneity among groups. The Fine and Gray model was utilized to estimate the subdistribution hazard ratio and 95% confidence interval. This study included 701 bevacizumab, 463 ranibizumab, and 984 aflibercept users. After IPTW, all covariates were well-balanced. All three anti-VEGF agents had a low and comparable number per 100 person-years of major adverse cardiac events, heart failure, thromboembolic events, major bleeding, all-cause admission, and all-cause death (all P > 0.05). No significant differences in long-term change of systolic and diastolic blood pressure, low-density lipoprotein, estimated glomerular filtration rate, and alanine transaminase (all P for interaction > 0.05) were observed among groups. Bevacizumab, ranibizumab, and aflibercept had a good systemic safety profile in this study. All groups showed a low and similar SAE risk and no differences in their long-term change of laboratory data. Therefore, these anti-VEGF agents could be prescribed safely to patients with AMD.

Subfoveal neurosensory detachment flattening and observe (SNF-Ob) approach for the management of Ci-DMO - a multicentric study.

To understand subfoveal neurosensory detachment flattening and observe (SNF-Ob) strategy and its relationship with visual acuity in the management of centre-involved diabetic macular oedema (Ci-DMO). This was a multicentric retrospective observational study. We reviewed data of 188 eyes of 130 patients who presented with Ci-DMO with subfoveal neurosensory detachment (NSD) and treated with intravitreal anti-vascular endothelial growth factor (anti-VEGF) agents or steroids. The primary outcome was best corrected visual acuity (BCVA) measured at the time of the first subfoveal neurosensory detachment flattening (SNF) and at the end of follow-up. Eyes that achieved 20/50 (LogMAR = 0.40) or better at first SNF had mean LogMAR BCVA 0.38 ± 0.21, 0.24 ± 0.11 and 0.21 ± 0.15 at baseline, at the time of first SNF, and at the end of the last follow-up respectively. Mean LogMAR BCVA significantly improved from baseline to first SNF (p < 0.0001; 95% CI 0.115-0.183) and at the end of the last follow-up (p < 0.0001; 95% CI 0.126-0.213) with a change of Early Treatment Diabetic Retinopathy Study (ETDRS) 10 letters. There was no significant difference in improvement in BCVA from the first SNF and at the end of the last follow-up (p = 0.0781; 95% CI -0.002 to 0.046). Eyes presenting with Ci-DMO and subfoveal NSD are unlikely to improve at SNF with BCVA > 20/50 (LogMAR = 0.40). Further evidence is needed before the combination of good BCVA and SNF may be considered as endpoint of pharmacological therapy for DMO.

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

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. 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. 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. Compared with IVR, IVB is likely to control the severity of ROP with a single treatment.

Diabetic macular edema: Upcoming therapies.

Diabetic macular edema (DME) is a serious vision-threatening complication that can arise at any stage of diabetic retinopathy. Primary treatment involves anti-vascular endothelial growth factor (VEGF) agents, which are highly effective but associated with challenges, such as the need for frequent injections, relapses, and resistance to therapy. Therefore, there has been a growing interest in developing new treatments that offer similar or superior outcomes in DME. This review article explores emerging treatments, including WNT agonists, gene therapy, protein inhibitors, and, most importantly, the first-ever non-invasive and oral drugs. The evolving therapies in diabetic retinopathy offer hope for continued improvement in vision loss associated with one of the most common chronic conditions worldwide.

Efficacy and safety of faricimab for neovascular age-related macular degeneration: a systematic review and network meta-analysis

ObjectiveTo evaluate the efficacy and safety of faricimab compared with other anti-vascular endothelial growth factor (anti-VEGF) agents in treating neovascular age-related macular degeneration (nAMD) patients.Methods and analysisA systematic review (SR)...