anti-VEGF Therapy Research Articles

Unexpected retinal fluid compartment responses with anti-VEGF therapy in polypoidal choroidal vasculopathy: a case report of four patients

This case series describes responses to faricimab treatment in opposite directions in different fluid compartments in four patients with polypoidal choroidal vasculopathy (PCV). Despite reductions in retinal fluid (SRF) and stable visual acuity following treatment, all patients developed retinal pigment epithelium (RPE) elevation. Over a 12–15 months follow-up, three patients exhibited a gradual decrease in RPE elevation, with one case resolving completely. These findings suggest that fluid compartments in PCV may respond differently to treatment and add to the understanding of PCV by highlighting the complex interplay between different retinal fluid compartments in response to treatment.

Randomized Clinical Trial of Intraocular Pressure-Lowering Medications on Preventing Spikes in Intraocular Pressure Following Intravitreal Anti-Vascular Endothelial Growth Factor Injections.

Intravitreal injections of anti-vascular endothelial growth factor (anti-VEGF) agents are a primary management option for retinal diseases. Acute elevation of intraocular pressure (IOP) is a complication associated with these injections that should be considered. This study investigated and compared the prophylactic effects of fixed combination anti-glaucoma medication on IOP spikes following intravitreal anti-VEGF injections. This randomized double-blind clinical trial included one eye of each participant indicated for treatment with intravitreal injection of anti-VEGF agents (bevacizumab, aflibercept, and ranibizumab) and randomly allocated to one of the three prophylactic anti-glaucoma medications, with each drug further divided into one- and two-drop regimens before intravitreal injection. Participants with allergies or contraindications to medications were excluded from the pretreatment groups and were invited to participate in the control group. The study involved 308 participants: 89 in the dorzolamide/timolol group, 86 in the brimonidine/timolol group, 101 in the brinzolamide/brimonidine group, and 32 in the control group. Baseline characteristics and IOP were comparable across all groups. In the prophylactic premedication groups, mean IOP at 30min were within 21mmHg and returned to their baseline at 1h. Mean IOP measurements between baseline and 30min in the brimonidine/timolol two-drop regimen were not significantly different: 13.72 ± 4.63 vs 15.11 ± 4.39mmHg, p = 0.096. In the control group, IOP significantly increased from baseline at 30min and 1h post-injection: 14.31 ± 4.10, 22.15 ± 8.64, and 18.36 ± 7.52mmHg, respectively, p < 0.001. Topical fixed combination anti-glaucoma medication used as a prophylactic treatment before intravitreal anti-VEGF injections significantly prevented IOP spikes post-injection, with a comparable effect among three medications. Prophylactic treatment of IOP spikes should be considered as standard care to prevent further damage in patients with compromised retinal vascular and optic nerve perfusion. TCTR20241005001, retrospectively registered.

Second-line therapies in advanced hepatocellular carcinoma following first-line atezolizumab and bevacizumab: multicenter single institution cohort experience.

Atezolizumab plus bevacizumab (A/B) received FDA approval as the first-line therapy for patients with advanced hepatocellular carcinoma (HCC) in 2020. However, optimal subsequent treatment options are unclear. Here, we describe clinical outcomes of advanced HCC patients following first-line treatment with A/B. We conducted a multi-site analysis of patients with HCC treated with first-line A/B between January 2018 and December 2022 at Mayo Clinic. This study cohort included all patients receiving second-line systemic therapy after A/B. Median overall survival (OS) and time-to-treatment discontinuation (TTD) were estimated using the Kaplan-Meier method. Child Pugh (CP) scores are also described at diagnosis, prior to first line, and prior to second-line therapy. Of the 342 patients who received A/B, 107 (31.3%) received second-line treatments including anti-VEGF therapy or immune checkpoint inhibitor (ICI) and were included in the final analysis. Median OS for all patients was 11.1 months from initiation of second-line therapy. Median OS was 10.7 months (95% CI: 7.2-12.8) and 15.7 months (95%CI: 6.8-NE) for those receiving anti-VEGF inhibitors and ICI ( P = .50). Median TTD for second-line therapies was 2.4 months (95% CI: 1.7-3.3) and 2.6 months (95% CI: 1.5-5.1) for anti-VEGF inhibitors and ICI, respectively (P = .87). In multivariate analyses, CP was significantly associated with survival. Following first-line A/B treatment, there is no statistically significant difference in survival between ICI and anti-VEGF therapy, nor in time to treatment discontinuation. CP score remains an important prognostic tool.

Development and validation of CNN-MLP models for predicting anti-VEGF therapy outcomes in diabetic macular edema

Diabetic macular edema (DME) is a common complication of diabetes that can lead to vision loss, and anti-vascular endothelial growth factor (anti-VEGF) therapy is the standard of care for DME, but the treatment outcomes vary widely among patients. This study collected optical coherence tomography (OCT) images and clinical data from DME patients who received anti-VEGF treatment to develop and validate deep learning (DL) models for predicting the anti-VEGF outcomes in DME patients based on convolutional neural network (CNN) and multilayer perceptron (MLP) combined architecture by using multimodal data. An Xception-MLP architecture was utilized to predict best-corrected visual acuity (BCVA), central subfield thickness (CST), cube volume (CV), and cube average thickness (CAT). Mean absolute error (MAE), mean squared error (MSE) and mean squared logarithmic error (MSLE) were employed to evaluate the model performance. In this study, both the training set and the validation set exhibited a consistent decreasing trend in MAE, MSE, and MSLE. No statistical difference was found between the actual and predicted values in all clinical indicators. This study demonstrated that the improved CNN-MLP regression models using multimodal data can accurately predict outcomes in BCVA, CST, CV, and CAT after anti-VEGF therapy in DME patients, which is valuable for ophthalmic clinical decisions and reduces the economic burden on patients.

Faricimab maintains substance integrity and sterility after compounding and storage in two different polypropylene syringe types.

Compounding and storage of intravitreal anti-vascular endothelial growth factor (anti-VEGF) agents in syringes is commonly performed in an off-label manner. However, the preservation of compound integrity and microbiological safety must be guaranteed. The aim of this study was to compare the chemical and physical stability, sterility and binding affinity to vascular endothelial growth factor (VEGF) and angiopoietin-2 (Ang-2) of faricimab, a novel bispecific anti-VEGF/Ang-2 biologic, after compounding and storage in two different polypropylene syringe types for up to 28 days. Faricimab was compounded into silicone oil-free and silicone oil-containing polypropylene syringes under controlled aseptic clean room conditions and stored under light protection at 2-8 °C for up to 28 days. Compound integrity was analysed by size exclusion chromatography, nano differential scanning fluorimetry, UV-vis and dynamic light scattering. The analysis of the simultaneous binding of VEGF and Ang-2 was performed by grating-coupled interferometry. Additionally, samples were tested for sterility and presence of bacterial endotoxins. One-way ANOVA test was used to analyse statistical significance (p ≤ 0.05). No significant differences in VEGF and ANG-2 binding affinity were found in faricimab samples stored in either syringe type after 28 days compared to control. Chemical and physical stability testing revealed no statistically significant variation. Furthermore, sterility and the absence of bacterial endotoxins could be maintained. Our findings confirm the pharmaceutical safety of compounded faricimab after storage for up to 28 days. This may facilitate a cost-effective off-label use of faricimab in clinical practice while maintaining safety in the treatment of patients.

Real-World Outcomes of Different Types of Treatment for Diabetic Macular Edema Before and After Approval of Anti-Vascular Endothelium Growth Factor Agents.

Background/Objectives: The object of this study was to determine the outcomes of treatments other than anti-vascular endothelial growth factor (VEGF) therapy for diabetic macular edema (DME) before and after the approval of anti-VEGF therapy in Japan. Methods: This was a retrospective study registered in the database of the Survey of Treatment for DME (STREAT-DME). A total of 1683 patients treated from 2010 to 2017 were included. The patients were divided into two groups: (1) a pre-group, treated before the approval of anti-VEGF agents (2010-2013, n = 771), and (2) a post-group (2014-2017, n = 912). Each group was further categorized based on best-corrected visual acuity (BCVA): (i) improved from poor (>0.3 logMAR units) to good (≤0.3 logMAR units) or (ii) decreased from good to poor. Results: In the pre-group, 18.5% of patients improved from poor to good BCVA out of the total patient population (p < 0.0001), along with 17.3% out of those administered anti-VEGF therapy (p = 0.139), 20.5% of those administered a sub-tenon injection of triamcinolone acetonide (STTA, p = 0.02), 17.7% (p = 0.20) of those administered photocoagulation, and 14.2% of those who underwent pars plana vitrectomy (PPV, p = 0.0001). In the post-group, 21.8% had improved BCVA out of the total patient population (p < 0.0001), along with 27.2% of those undergoing anti-VEGF therapy (p < 0.0001), 16.7% of those administered STTA (p < 0.0001), and 27.2% of those who underwent PPV (p < 0.0001). Conclusions: STTA and PPV are effective to a certain extent, even after the approval of anti-VEGF agents.

Preclinical evaluation of NG101, a potential AAV gene therapy for wet age-related macular degeneration

Age-related macular degeneration (AMD) is a leading cause of vision loss in individuals over the age of 55. Approximately 10%-15% of AMD patients develop choroidal neovascularization (CNV), leading to wet AMD (wAMD), which accounts for nearly 90% of AMD-related blindness. Inhibition of vascular endothelial growth factor (VEGF) is the standard treatment for wAMD. However, the frequent administration of the current treatment imposes a significant burden on wAMD patients. Therefore, there is an unmet need for treatments that require less-frequent administration. Here, we present findings on the safety and efficacy of NG101, a recombinant adeno-associated virus (rAAV) vector encoding aflibercept, an anti-VEGF agent, for wAMD therapy. A single subretinal injection of NG101 effectively reduced CNV lesion leakage and size at doses as low as 1×106 in mouse and 3×109 viral genomes per eye in cynomolgus monkeys. In cynomolgus monkeys, NG101-derived aflibercept expression in ocular tissues persisted for 1 year post-injection, indicating sustained therapeutic potential. Biodistribution analysis revealed that NG101 was primarily localized in ocular tissues. Only mild and transient ocular inflammatory responses were observed. Overall, these findings suggest that NG101, with its efficacy at low doses and sustained expression, is a promising therapeutic candidate for wAMD.

Outcomes of Anti-VEGF Therapy in Eyes with Diabetic Macular Edema, Vein Occlusion-Related Macular Edema, and Neovascular Age-Related Macular Degeneration: A Systematic Review

Outcomes of Anti-VEGF Therapy in Eyes with Diabetic Macular Edema, Vein Occlusion-Related Macular Edema, and Neovascular Age-Related Macular Degeneration: A Systematic Review

Clinical Characteristics and Treatment Outcomes in Unilateral Coats disease – a Global Collaborative Study

To evaluate the clinical outcomes and prognostic factors in unilateral Coats disease in the era of anti-VEGF therapy. Global, multicenter, retrospective case series. 656 eyes of 656 subjects with Coats disease were included in this study. Exclusion criteria were Coats disease secondary to retinitis pigmentosa as well as bilateral cases. Clinical data from patients with Coats disease were collected from 20 ophthalmic practices around the world. We compared early-stage (stage 1-2) and advanced-stage (stage 3-5) Coats disease in terms of clinical characteristics and treatment modalities. Functional outcomes include achieving visual acuity (VA) of 0.3 logMAR or better and VA improvement or stability. Anatomical failure was defined as the development of phthisis, chronic retinal detachment, massive fibrosis, or the requirement for enucleation. Subjects with early-stage disease were significantly older, with a mean age of 17.4 ± 17.8 years, compared to 7.1 ± 7.1 years in the advanced-stage group (p < 0.001). There was a male predominance in both early and advanced stages (84.7%). Advanced disease was associated with a higher incidence of strabismus (20.2% vs. 6.7%, p < 0.001) and leukocoria (12.3% vs. 3.2%, p < 0.001). More subjects with early-stage disease received laser photocoagulation as monotherapy (44.7% vs. 21.1%, p < 0.001). Additionally, early-stage disease received more sessions of intravitreal anti-VEGF injections as adjunct therapy (4.4 ± 6.2 vs. 2.7 ± 2.1, p = 0.005). Factors associated with poorer functional outcomes included worse presenting visual acuity, advanced disease stage, and the presence of a foveal nodule. Worse presenting visual acuity and advanced disease stage was associated with lower likelihood of anatomical success while combination therapy increased the odds of anatomical success. Unilateral Coats disease predominantly affects males, regardless of disease stage. Identifying a foveal nodule is crucial for visual prognosis. Laser photocoagulation remains the primary treatment. While anti-VEGF may prevent enucleation, its role in early-stage disease requires further clarification.

Factors affecting the duration of air tamponade following vitreoretinal surgery.

Air as a tamponade in pars plana vitrectomy (PPV) is increasingly preferred due to its quick rehabilitation time. We aim to examine the factors affecting the absorption time of air tamponade. The study included 82 eyes from 78 patients who underwent PPV with air used as the tamponade. All patients underwent detailed ophthalmic examinations preoperatively and on the first and third postoperative days. The study evaluated demographic and clinical characteristics, surgical indications, and whether concurrent phacoemulsification surgery was performed. A single surgeon conducted all surgeries and examinations. The intraocular air percentage and volume in milliliters were determined. Patients were divided into two groups based on whether the intraocular air volume was reduced by more or less than 1.5ml from the first to the third day. Concurrent cataract surgery was performed in 35.4% of the eyes. All 82 eyes were pseudophakic at the end of the surgery. The mean air percentage in the eyes was 68.90% on the first day and 47.29% on the third day. Only the concurrent cataract surgery significantly shortened the air elimination time (p = 0.005). Other factors, such as diabetic retinopathy, glaucoma, and concurrent anti-VEGF therapy, did not show a significant impact. The study concluded that concurrent cataract surgery notably reduces air tamponade duration after PPV. We think these findings are crucial for patient selection and surgical planning, especially in cases where maintaining a longer tamponade duration is critical, such as in retinal detachment or macular hole surgeries. What is known The use of air as tamponade is becoming increasingly widespread in vitreoretinal surgery. What is new Compared to performing the surgeries separately, air tamponade shows faster absorption in concurrent cataract and vitreoretinal surgery. Factors such as diabetic retinopathy, glaucoma, and concurrent anti-VEGF therapy do not significantly affect the absorption time of intraocular air after vitreoretinal surgery.

Anti-Vascular Endothelial Growth Factor Combined with Ocular Steroid Therapy for Persistent Diabetic Macular Edema: A Systematic Review and Meta-Analysis

Purpose: Our purpose was to appraise the efficacy and safety of intravitreous vascular endothelial growth factor inhibitor (anti-VEGF) therapy combined with steroids for persistent diabetic macular edema. Methods: A systematic review was conducted of the research evaluating the combination therapy of anti-VEGF and steroids for persistent diabetic macular edema compared to anti-VEGF alone. A meta-analysis was performed using a protocol registered in PROSPERO (CRD42023476333). Continuous and binary variables were extracted. Results were expressed as the mean difference (MD) and risk ratio (RR). Results: A total of 9 trials with 537 eyes were included. The MDs of improvement in best-corrected visual acuity (BCVA) at 1/2/3/6/9/12 months between the combined and monotherapy groups were 1.33 (95% CI [−1.31,3.96]), 3.03 (95% CI [0.01, 6.06]), −0.37 (95% CI [−4.74, 4.00]), −1.37 (95% CI [−4.65, 1.91]), 1.05 (95% CI [−3.68, 5.77]), and 1.70 (95% CI [−3.52, 6.93]). The MDs concerned with a central retinal thickness (CMT) decline in at 1/2/3/6/9/12 months between the two groups were −47.33, 95% CI [−94.35, −0.32]), −89.19 (95% CI [−114.38, −64.00]), −58.84 (95% CI [−96.93, −20.74]), −57.23 (95% CI [−102.62, −11.84]), −40.59 (95% CI [−80.59, −0.58]), and −38.89 (95% CI [−77.38, −0.40]), respectively. Furthermore, the combined group obtained higher relative risks of experiencing events with high intraocular pressure and progressed cataracts. Conclusions: Anti-VEGF combined with ocular steroids showed a significant advantage in improving the retinal anatomical structure compared to anti-VEGF monotherapy for persistent diabetic macular edema. However, as the treatment period extended, the combination treatment was no more effective than monotherapy after 2 months, with more severe side effects.

Beneficial Effects of Micronutrient Supplementation in Restoring the Altered Microbiota and Gut-Retina Axis in Patients with Neovascular Age-Related Macular Degeneration-A Randomized Clinical Trial.

Background/Objectives: Age-related macular degeneration (AMD) is a leading cause of visual impairment in the elderly and is characterized by a multifactorial etiology. Emerging evidence points to the potential involvement of the gut-retina axis in AMD pathogenesis, prompting exploration into novel therapeutic strategies. This study aims to investigate the effects of some micronutrients (such as lutein and zeaxanthin) and saffron (as a supplement)-known for their anti-inflammatory properties-on ophthalmological and microbial parameters in neovascular AMD (nAMD) patients. Methods: Thirty naive nAMD patients were randomized to receive daily micronutrient supplementation alongside anti-VEGF (vascular endothelial growth factor) therapy, or anti-VEGF treatment alone, over a 6-month period, with comparisons made to a healthy control (HC) group (N = 15). Ophthalmological assessments, biochemical measurements, and stool samples were obtained before and after treatment. Gut microbiota (GM) characterization was performed using 16S rRNA sequencing, while short-chain fatty acids (SCFAs), medium-chain fatty acids (MCFAs), and long-chain fatty acids (LCFAs) were analyzed with a gas chromatography-mass spectrometry protocol. Results: Compared to HC, nAMD patients exhibited reduced GM alpha diversity, altered taxonomic composition, and decreased total SCFA levels, in addition to elevated levels of proinflammatory octanoic and nonanoic acids. Micronutrient supplementation was associated with improved visual acuity relative to the group treated with anti-VEGF alone, along with a decrease in the total amount of MCFAs, which are metabolites known to have adverse ocular effects. Conclusions: In conclusion, despite certain limitations-such as the limited sample size and the low taxonomic resolution of 16S rRNA sequencing-this study highlights compositional and functional imbalances in the GM of nAMD patients and demonstrates that micronutrient supplementation may help restore the gut-retina axis. These findings suggest the therapeutic potential of micronutrients in enhancing ocular outcomes for nAMD patients, underscoring the complex interaction between GM and ocular health.

Clinical Features and Treatment Outcomes of Choroidal Osteoma in Asian Indians (80 Patients)

Purpose: To describe the demographic and clinical characteristics, and treatment outcomes of choroidal osteoma in Indian patients. Methods: This cross-sectional hospital-based study included 80 patients (100 eyes) between 2nd October 2012 and 15th May 2024. Results: Forty-nine (61%) participants were female, and 31 (39 %) were male. The most common age group was the second decade (n=27, 34%). Tumor ossification with intact RPE was observed in 37 (44%) eyes and tumor deossification with/without RPE atrophy was observed in 55 (65%). Associated features observed were choroidal neovascularization (CNV) in 40 (40%) eyes, subretinal fluid without CNV in 4 (4%) eyes, and documented tumor growth in 6 (6%) eyes (mean interval, 4 years). At 4 and 8 years, Kaplan–Meier analysis revealed tumor growth in 18% and 38% of eyes, respectively. Of the 83 eyes, OCT showed the presence of choroidal lamellae in ossified zones in 30 eyes (100%), CNV in 40 (48%) eyes, SRF without CNV or growth in 8 (10%) eyes, and RPE atrophy with deossification in 53 (64%) eyes. Treatment included intravitreal anti-VEGF therapy for CNV in 39 eyes, transpupillary thermotherapy in 3, and focal laser photocoagulation in one eye to the perifoveal leaning edge with SRF without CNV. The mean BCVA changed from 0.4 to 0.6 logMAR units (6/15 to 6/24 Snellen’s equivalent) at a mean follow-up of 19 months (3-149 months). Conclusion: Choroidal osteoma is a unilateral condition observed in females. Although benign, the presence of CNV, SRF, or tumor growth requires treatment and periodic surveillance.

Pooled Multicenter Safety Analysis of Lupin's Intravitreal Biosimilar Ranibizumab (Ranieyes) in Chorioretinal Vascular Diseases.

This study aims to evaluate the ocular and systemic safety profiles of intravitreal biosimilar ranibizumab Ranieyes (Lupin Pharmaceuticals, Mumbai, India) in real-world clinical settings across multiple chorioretinal vascular diseases, including neovascular age-related macular degeneration (nAMD), diabetic macular edema (DME), and retinal vein occlusion (RVO) in adults. We conducted a retrospective, consecutive, interventional, uncontrolled multicenter study using data from three hospital networks in India. A total of 1401 eyes received 2194 injections of Ranieyes between June 2022 and November 2023. Patients were followed for a minimum of 6months, and data on ocular and systemic adverse events (AEs) were collected and analyzed. The study population included 636 male patients and 533 female patients, with a mean age of 58.63 ± 11.54years. The average number of injections per eye was 1.49 ± 0.23, with the highest frequency in the nAMD group (mean of 2.3 ± 0.23 injections per eye) over 6months. Non-serious adverse events (nsAEs) were observed in 26.83% of injections, with mild ocular pain and transient blurring of vision being the most common. Serious ocular adverse events were rare, occurring in 0.85% of eyes, with retinal pigment epithelial tear (RPE TEAR) being the most frequent. Systemic adverse events were noted in 5.03% of patients, and all but one were non-serious. One patient developed non-fatal myocardial infarction, the causal relationship of which, however, was not established with the intravitreal agent used. No cases of endophthalmitis were observed. This large-scale, real-world study demonstrates that Ranieyes is a safe intravitreal antivascular endothelial growth factor (anti-VEGF) agent across various chorioretinal vascular diseases. The safety profile of Ranieyes is consistent with that of the reference product, making it a viable option in resource-constrained settings.

The analysis of foveal microvascular anomalies in retinopathy of prematurity after anti-vascular endothelial growth factor therapy using optical coherence tomography angiography

BackgroundTo investigate the quantitative vascular and structural differences in the foveal region of the eyes in retinopathy of prematurity children with or without anti-vascular endothelial growth factor (VEGF) therapy and healthy children using optical coherence tomography angiography (OCTA).MethodsThis cross-sectional study analyzed 75 eyes from 44 subjects, categorized into four groups: ROP children treated with Conbercept or Ranibizumab, spontaneously regressed ROP, and healthy age-matched children. Using spectral-domain OCT and OCTA, we assessed parameters like central foveal thickness (CFT), foveal avascular zone (FAZ), superficial/deep capillary plexus (SCP/DCP), and choroidal vessel density (VD) at the fovea. Correlations between foveal microvasculature, preterm status and visual acuity were evaluated.ResultsSignificant differences were found in FAZ area, CFT, and VD-SCP (parafoveal) among the groups. The FAZ area was smaller in ROP children (with/without treatment) than in healthy counterparts(p = 0.009). CFT was higher in the Ranibizumab and spontaneously regressed groups compared to healthy ones (p = 0.043, p = 0.037), while Conbercept-treated children showed no significant difference (p = 0.886). Foveal VD trends were higher in groups A, B, and C compared to group D. FAZ area correlated negatively with CFT, VD-SCP (foveal), and VD-DCP (foveal) (p < 0.001, p < 0.001, p = 0.001), and positively with choroidal VD (p = 0.012). CFT showed positive correlations with VD-SCP (foveal) and VD-DCP (foveal) (p = 0.003, p = 0.001).ConclusionROP children exhibit a smaller FAZ area compared to healthy group, with no significant difference noted when comparing the use of different anti-VEGF agents. ROP children have a thicker CFT than healthy children, except for those treated with Conbercept. Furthermore, microvascular irregularities were correlated with central foveal thickness.

Impact of anti-VEGF treatment-free interval during the first year on 5-year outcomes in eyes with branch retinal vein occlusion.

This study aims to analyze the impact of longest treatment-free interval (TFI) between anti-vascular endothelial growth factor (anti-VEGF) injections during the first year of treatment on 5-year best-corrected visual acuity (BCVA) and recurrence of macular edema (ME) in eyes with ME secondary to branch retinal vein occlusion (BRVO). A retrospective study including eyes with BRVO, minimum of 5-year follow-up, and available optical coherence topography (OCT) scans. Eyes underwent anti-VEGF loading dose therapy and were treated and monitored with an OCT-guided PRN regimen. Those with a history of ocular comorbidities were excluded. Total of 60 patient eyes, with 40 females and average age of 71.75 ± 11.07 years. TFI among eyes was 1 month (20%); > 1-2 months (23%); > 2-3 months (18%); > 3-4 months (17%), and >4 months (22%). Forty-three (72%) eyes experienced ME recurrence during the five-year period. Multivariate linear regression shows that TFI (-0.02 [-0.03-0.00], p = 0.021) and baseline BCVA (0.37 [0.08-0.66], p = 0.014) are significant predictors of 5-year BCVA. TFI (Cox Proportional Hazard Ratio 1.34 [1.04-1.72], p = 0.023) and number of injections in the first year (Cox Proportional Hazard Ratio 1.76 [1.01-3.06], p = 0.045) were significant predictors of ME recurrence. Gender, age, type of injection, BCVA, and CMT did not influence recurrence. For eyes receiving anti-VEGF injections to treat ME secondary to BRVO, TFI is a significant predictor of 5-year BCVA and ME recurrence according to regression models. This study suggests more ME recurrence may be due to increased TFI or indicate more injections needed to treat severe BRVO.

Retinopathy of Prematurity: Incidence, Risk Factors, and Treatment Outcomes in a Tertiary Care Center.

Retinopathy of prematurity (ROP) remains a major cause of childhood blindness. Its pooled prevalence worldwide is 31.9%, and that of severe ROP is 7.5% among prematurely born babies. Investigating risk factors is essential for improving early detection and treatment outcomes. Purpose: To determine the frequency and stages of ROP cases and evaluate the treatment methods for premature infants at the Medical University of Vienna. Methods: In this retrospective study, 352 children who underwent ROP screening between 2018 and 2021 with a gestational age (GA) ≤ 32 weeks and/or a birth weight (BW) ≤ 1500 g were included. Results: ROP was found in 144 (40.9%) of the 352 screened premature infants, with 17 (4.8%) requiring treatment. Significant risk factors included GA and BW, while sex and pregnancy type were not significant. The mean GA was 27.7 ± 2.5 weeks, and the mean BW was 989.1 ± 359.7 g. Infants with ROP had a lower GA (25.9 ± 1.7 weeks) and BW (778.6 ± 262.4 g) than those without ROP (28.9 ± 2.2 weeks; 1134.9 ± 345.9 g). GA and BW were significantly lower in infants developing ROP (p < 0.001). Stage 2 ROP was the most common severity in 74 children (51.4%). Laser therapy was the most common first-line treatment, used in 11 infants (64.7%), followed by anti-VEGF therapy, used in 6 infants (35.3%). Children were treated within 1.0 ± 0.6 days on average. Of the 17 infants treated, 14 (82.4%) showed initial regression. Three infants (17.6%) required re-treatment: two with initial anti-VEGF therapy and one after laser therapy. Conclusions: The findings provide insights into ROP's prevalence and treatment preferences at a university tertiary care center. GA and BW were confirmed to be significant predictors, aiding in early detection and informing treatment decisions. These insights will enable comparisons with similar studies and contribute to improved patient care.

Anti-VEGF treatment outcome prediction based on optical coherence tomography images in neovascular age-related macular degeneration using a deep neural network.

Age-related macular degeneration (AMD) is a major cause of blindness in developed countries, and the number of affected patients is increasing worldwide. Intravitreal injections of anti-vascular endothelial growth factor (VEGF) are the standard therapy for neovascular AMD (nAMD), and optical coherence tomography (OCT) is a crucial tool for evaluating the anatomical condition of the macula. However, OCT has limitations in accurately predicting the degree of functional and morphological improvement following intravitreal injections. Artificial intelligence (AI) has been proposed as a tool for predicting the treatment response of nAMD based on OCT biomarkers. Our study focuses on the development and assessment of an AI model utilizing the DenseNet201 algorithm. The model aims to predict anatomical improvement based on OCT images before, and during anti-VEGF therapy. The training process involves two scenarios: (1) using only preinjection OCT images and (2) utilizing both OCT images before and during anti-VEGF therapy for model training. The outcomes of our investigation, involving 2068 images from a cohort of 517 Korean patients diagnosed with nAMD, indicate that the AI model we introduced surpassed the predictive performance of ophthalmologists. The model exhibited a sensitivity of 0.915, specificity of 0.426, and accuracy of 0.820. Notably, its predictive capabilities were further enhanced with the inclusion of additional OCT images taken after the first and second injections during the loading phase. The treatment prediction performance of the model was the highest when using all input modalities (before injection, and after the first and second injections) and concatenation-based fusion layers. This study highlights the potential of AI in assisting individualized and tailored nAMD treatment.

Correlation of retinal fluid and photoreceptor and RPE loss in neovascular AMD by automated quantification, a real-world FRB! analysis.

To quantify ellipsoid zone (EZ) loss during anti-VEGF therapy for neovascular age-related macular degeneration (nAMD) and correlate these findings with nAMD disease activity using artificial intelligence-based algorithms. Spectral domain optical coherence tomography (Spectralis, Heidelberg Engineering) images from nAMD treatment-naïve patients from the Fight Retinal Blindness! (FRB!) Registry from Zürich, Switzerland were processed at baseline and over 3 years of follow-up. An approved deep learning algorithm (Fluid Monitor, RetInSight) was used to automatically quantify intraretinal fluid (IRF), subretinal fluid (SRF) and pigment epithelial detachment (PED). An ensemble U-net deep learning algorithm was used to automated quantify EZ integrity based on EZ layer thickness. The impact of fluid volumes on EZ thickness and late-stages outcomes were calculated using Wilcoxon rank-sum tests, a linear mixed model and a longitudinal panel regression model. Two hundred and eleven eyes from 158 patients were included. The mean ± SD EZ loss area in the central 6 mm was 1.81 ± 2.68 mm2 at baseline and reached 6.21 ± 6.15 mm2 at month 36. Higher fluid volumes (top 25%) of IRF and PED in the central 1 and 6 mm of the macula were significantly associated with more advanced EZ thinning and loss compared to the low fluid volume subgroup. The high SRF subgroup in the linear regression model showed no statistically significant association with EZ integrity in the central macula; however, the longitudinal analysis revealed an increased EZ thickness with no additional loss. Intraretinal fluid and PED volumes and their resolution pattern have an impact on alteration of the underlying EZ layer. AI-supported quantifications are helpful in quantifying early signs of macular atrophy and providing individual risk profiles as a basis for tailored therapies for optimized visual outcomes.

Pneumatic displacement and intravitreal anti-vascular endothelial growth factor, with or without intravitreal tissue plasminogen activator, injection for submacular hemorrhage

Purpose: To evaluate the outcomes of intravitreal gas and anti-vascular endothelial growth factor (VEGF), with or without tissue plasminogen activator (tPA), injection for submacular hemorrhage (SMH). Methods: We retrospectively enrolled patients with SMH treated with intravitreal gas and anti-VEGF, with or without tPA (tPA and non-tPA groups, respectively), injection between 2014 and 2021 and data were collected at the preoperative visit and at 1-, 3-, 6-, and 12-month follow-ups. The primary outcome was the final best-corrected visual acuity (BCVA), and the secondary outcomes were central subfield thickness (CST), degree of blood displacement, and incidence of vitreous hemorrhage (VH). Results: Herein, 38 eyes received intravitreal gas, anti-VEGF, and tPA injections whereas 89 received intravitreal gas and anti-VEGF injections. At 12 months, no significant intergroup difference was detected (p=0.94), except the slightly greater CST change in the non-tPA group (p=0.03). Complete SMH displacement occurred in 35 (tPA=92.1%) and 89 (non-tPA=89.9%) eyes, with higher VH incidence in the non-tPA group (OR 7.03, p=0.004). Conclusion: In pneumatic displacement combined with anti-VEGF therapy in SMH, adjunctive tPA use did not alter the visual and anatomical outcomes although the VH risk in large SMH was reduced.