PROSPECTIVE TRIAL OF HOME OPTICAL COHERENCE TOMOGRAPHY-GUIDED MANAGEMENT OF TREATMENT EXPERIENCED NEOVASCULAR AGE-RELATED MACULAR DEGENERATION PATIENTS.

PURPOSE: To evaluate the impact of home optical coherence tomography (OCT)-guided patient management on treatment burden and visual outcomes. METHODS: An interventional trial was conducted to compare frequency of treatment and visual acuity for the neovascular age-related macular degeneration patients before and during use of home optical coherence tomography over a period of 6 months. Patient adherence to regular scanning was measured by the number of scans performed per week. The characteristics of episodes of fluid recurrence and classification of typical fluid volume trajectories were performed. RESULTS: Twenty-seven eyes (21 with diagnosis of neovascular age-related macular degeneration and one converted during the study), of 15 patients were monitored for 6 months, scanning at 6.2 times/week per eye and yielding 4,435 scans of which 91.2% were eligible for artificial intelligence-based fluid volume quantification. Total number of monitoring weeks before and during the study were 1,555 and 509. The mean (SD) number of weeks per injection before and during home OCT management were 8.0 (4.7) and 15.3 (8.5) (P = 0.004), respectively. The mean (SD) visual acuity change before and during home OCT-based management was 3.5 (12.0) letters and 0.0 (9.5) letters (P = 0.45), respectively, showing no significant impact on visual acuity. CONCLUSION: For the first time, remote patient monitoring with a home OCT allowed personalized management of neovascular age-related macular degeneration. This study showed significant reduction in treatment burden while maintaining stable visual acuity.

Switch to faricimab after initial treatment with aflibercept in eyes with neovascular age-related macular degeneration.

PURPOSE: To investigate the efficacy and outcomes of switching neovascular age-related macular degeneration (nAMD) patients from aflibercept to faricimab, focusing on visual acuity, retinal fluid management, and treatment intervals. The primary aim was to assess the early outcomes in nAMD patients refractory to aflibercept and explore faricimab's potential as a longer-lasting therapeutic alternative. METHODS: A single-center retrospective study was conducted on 50 refractory nAMD patients at Cleveland Clinic Abu Dhabi from September 2022-May 2023. Patients were switched from aflibercept to faricimab, having met specific criteria for refractory nAMD. The study analyzed best-corrected visual acuity (BCVA), central subfield thickness (CST), and fluid changes post-switch, using Optical Coherence Tomography (OCT). RESULTS: After three faricimab injections, significant reductions in CST were observed, with a notable decrease in retinal fluid. The mean BCVA remained stable throughout the study period. Although there was a decrease in the maximum pigment epithelial detachment (PED) height, it was not statistically significant. Treatment intervals post-switch showed that the majority of patients maintained or extended their treatment intervals, with a significant proportion achieving resolution of intraretinal fluid (IRF) and subretinal fluid (SRF). CONCLUSIONS: Switching to faricimab from aflibercept in refractory nAMD patients led to significant improvements in retinal fluid management and CST, with stable BCVA outcomes. Faricimab presents a promising alternative for patients requiring frequent aflibercept injections, potentially offering a more manageable treatment regimen with extended dosing intervals. This study highlights the need for personalized therapeutic strategies in nAMD treatment, though further research is necessary to optimize treatment switches.

Prediction of Post-Treatment Visual Acuity in Age-Related Macular Degeneration Patients With an Interpretable Machine Learning Method.

Purpose: We evaluated the features predicting visual acuity (VA) after one year in neovascular age-related macular degeneration (nAMD) patients. Methods: A total of 527 eyes of 506 patients were included. Machine learning (ML) models were trained to predict VA deterioration beyond a logarithm of the minimum angle of resolution of 1.0 after 1 year based on the sequential addition of multimodal data. BaseM models used clinical data (age, sex, treatment regimen, and VA), SegM models included fluid volumes from optical coherence tomography (OCT) images, and RawM models used probabilities of visual deterioration (hereafter probability) from deep learning classifiers trained on baseline OCT (OCT0) and OCT after three loading doses (OCT3), fluorescein angiography, and indocyanine green angiography. We applied SHapley Additive exPlanations (SHAP) for machine learning model interpretation. Results: The RawM model based on the probability of OCT0 outperformed the SegM model (area under the receiver operating characteristic curve of 0.95 vs. 0.91). Adding probabilities from OCT3, fluorescein angiography, and indocyanine green angiography to RawM showed minimal performance improvement, highlighting the practicality of using raw OCT0 data for predicting visual outcomes. Applied SHapley Additive exPlanations analysis identified VA after 3 months and OCT3 probability values as the most influential features over quantified fluid segments. Conclusions: Integrating multimodal data to create a visual predictive model yielded accurate, interpretable predictions. This approach allowed the identification of crucial factors for predicting VA in patients with nAMD. Translational Relevance: Interpreting a predictive model for 1-year VA in patients with nAMD from multimodal data allowed us to identify crucial factors for predicting VA.

Exploring the comparative regressive effects of aflibercept and faricimab on pigment epithelial detachment.

BACKGROUND: This study aimed to compare the regressive effects of aflibercept and faricimab on pigment epithelial detachment (PED) in patients with neovascular age-related macular degeneration. METHODS: In total, 41 eyes of 40 patients diagnosed with type 1 macular neovascularization were retrospectively analyzed using multimodal imaging. Of these, 23 eyes were treated with intravitreal aflibercept injections (IVA group), and 18 eyes were treated with intravitreal faricimab (IVFa group), with 3 consecutive injections administered as loading dose therapy. Before treatment and at 1, 2, and 3 months after the first treatment, the maximum height (MH) and maximum diameter (MD) of the PED were measured using optical coherence tomography in each treatment group. RESULTS: In the IVA group, the MH at baseline (215 ± 177 µm) was reduced to 141 ± 150 (P = 0.06), 119 ± 150 (P < 0.01), and 107 ± 150 µm (P < 0.0001) at 1, 2, and 3 months after treatment, respectively. Similarly, in the IVFa group, the MH decreased from 240 ± 195 µm before treatment to 165 ± 170 µm (P = 0.24), 139 ± 142 µm (P < 0.05), and 117 ± 112 µm (P < 0.01) at 1, 2, and 3 months after treatment, respectively. The reduction at 2 and 3 months was significant in both treatments. The mean changes of MH from baseline were -108 ± 142 µm in the IVA group and -124 ± 112 µm in the IVFa group, with no significant difference (P = 0.21). In both groups, the MD did not regress significantly. CONCLUSIONS: The results suggested that the MH of the PED between the IVA and IVFa groups regressed similarly after each loading therapy.

Efficacy and Durability of Faricimab in Naïve Eyes with Neovascular Age-Related Macular Degeneration.

INTRODUCTION: The aim of the study was to evaluate functional and anatomical changes in patients with neovascular age-related macular degeneration (nAMD) treated with a loading dose of faricimab intravitreal injections (IVIs). METHODS: Eighteen eyes of 18 patients with active macular neovascularization and nAMD were enrolled at the Ophthalmology Clinic of University G. D'Annunzio, Chieti-Pescara, Italy. All patients were scheduled for faricimab IVI as per label. Enrolled patients underwent complete ophthalmic evaluation, including optical coherence tomography, fluorescein angiography, and indocyanine green angiography. All measurements were evaluated at baseline (T0) and then monthly up to week 20 (T4). Main outcome measures were changes in best-corrected visual acuity (BCVA), central macular thickness (CMT), subfoveal choroidal thickness (SFCT), pigment epithelial detachments (PEDs) presence and maximum height (PED-MH), intraretinal fluid (IRF) presence, subfoveal subretinal fluid (SSRF) presence and thickness. RESULTS: BCVA improved and CMT reduced significantly during follow-up (p < 0.001). In addition, SFCT decreased significantly (p = 0.031). Between T0 and T4, SSRF presence reduced from 55.6 to 16.7% (p = 0.045); IRF presence changed from 50 to 22.2%, respectively (p = 0.074). PED-MH was reduced in 58.8% of patients at T4. At week 20, 72.3% of patients were in the q12/q16 interval. CONCLUSION: Faricimab showed efficacy in the treatment of naïve nAMD patients with an improvement of anatomical and functional parameters and a treatment interval after the loading phase equal or greater than 12 weeks in the majority of patients.

EFFICACY AND SAFETY OF THE PROPOSED BIOSIMILAR AFLIBERCEPT, SDZ-AFL, IN PATIENTS WITH NEOVASCULAR AGE-RELATED MACULAR DEGENERATION: 52-Week Results From the Phase 3 Mylight Study.

PURPOSE: The Phase 3 Mylight study was designed to confirm clinical equivalence of proposed biosimilar aflibercept (SOK583A1; Sandoz [proposed biosimilar aflibercept, SDZ-AFL]) to its reference biologic (Eylea; Regeneron Pharmaceuticals, Inc; Bayer AG [reference aflibercept, Ref-AFL]). METHOD: Mylight was a prospective, double-masked, 2-arm, parallel Phase 3 study. Participants with neovascular age-related macular degeneration were randomized 1:1 to receive eight injections of SDZ-AFL (n = 244) or Ref-AFL (n = 240) over 48 weeks. The primary endpoint was mean change in best-corrected visual acuity score from baseline to Week 8. Secondary endpoints included anatomical outcomes, best-corrected visual acuity at Weeks 24 and 52, safety, and pharmacokinetics. RESULTS: Similarity in mean change in best-corrected visual acuity score was established between SDZ-AFL (n = 235) and Ref-AFL (n = 226) at Week 8 (difference: -0.3 [90% CI, -1.5 to 1.0]) and Week 52. No clinically meaningful differences occurred between groups in anatomical outcomes. Safety profiles were similar, with comparable incidences of treatment-related adverse events (SDZ-AFL: 2.5%; Ref-AFL: 2.9%). The incidence of anti-drug antibodies was similar between groups. Systemic free aflibercept concentrations 24 hours postdose were low and comparable between SDZ-AFL and Ref-AFL. CONCLUSION: Proposed biosimilar aflibercept matched reference aflibercept in efficacy, safety, and pharmacokinetics in participants with neovascular age-related macular degeneration. Therefore, this Phase 3 study confirmed biosimilarity of SDZ-AFL to Ref-AFL.

Aqueous Humor Cytokine Analysis in Age-Related Macular Degeneration After Switching From Aflibercept to Faricimab.

Purpose: To examine the changes in aqueous humor cytokine levels and clinical outcomes of switching from aflibercept to faricimab in eyes with neovascular age-related macular degeneration (nAMD). Methods: Fifty-four eyes of 54 patients with AMD undergoing treatment with aflibercept under a treat-and-extend (TAE) regimen were switched to faricimab and studied prospectively. Best-corrected visual acuity (BCVA; in logarithm of the minimum angle of resolution), central retinal thickness (CRT), central choroidal thickness (CCT), and exudative status were analyzed using optical coherence tomography. Aqueous humor was collected before and after the switch, and angiopoietin-2 (Ang-2), placental growth factor (PlGF), and vascular endothelial growth factor (VEGF) A levels were measured. Results: After switching from aflibercept to faricimab, exudative changes improved in 28 eyes (52%), remained stable in eight eyes (15%), and worsened in 18 eyes (33%). BCVA changed from 0.27 ± 0.31 to 0.26 ± 0.29 (P = 0.46), CRT decreased from 306.2 ± 147.5 µm to 278.6 ± 100.4 µm (P = 0.11), and CCT changed from 189.5 ± 92.8 µm to 186.8 ± 93.9 µm (P = 0.21). VEGF-A levels were below the detection sensitivity in many cases throughout the pre- and post-switching periods. Ang-2 significantly decreased from 23.8 ± 23.5 pg/mL to 16.4 ± 21.9 pg/mL (P < 0.001), and PlGF significantly increased from 0.86 ± 0.85 pg/mL to 1.72 ± 1.39 pg/mL (P < 0.001). Conclusions: Switching from aflibercept to faricimab in patients with nAMD may not only suppress VEGF-A but also Ang-2 and reduce exudative changes.

MICROVASCULAR CHANGES IN TREATMENT-NAÏVE NONEXUDATIVE MACULAR NEOVASCULARIZATION COMPLICATED BY EXUDATION.

PURPOSE: To assess differences in choriocapillaris (CC) and macular neovascularization (MNV) optical coherence tomography angiography quantitative parameters between long-term persistently nonexudative MNVs (NE-MNVs) and long-term activated NE-MNVs in age-related macular degeneration. METHODS: Age-related macular degeneration patients with treatment-naïve NE-MNVs with >2 years of follow-up and no evidence of exudation within the first 6 months from diagnosis were retrospectively recruited. Two groups were considered according to the occurrence (EX group) or not (NE group) of exudation within the first 2 years of follow-up. Segmentation of the MNV and of the perilesional CC were obtained from enface optical coherence tomography angiography acquisitions at diagnosis and at 6-month follow-up. OCT B-scan images of the MNV were also collected. Fractal ratio was defined as the ratio between MNV fractal dimension (FrD) and CC FrD. RESULTS: Fifty (50) eyes were included (20 EX group and 30 NE group). EX group showed higher flow deficit density and flow deficit number at the 6-month follow-up. It also showed higher MNV FrD, lower CC FrD, and higher fractal ratio at the 6-month follow-up. The fractal ratio significantly increased at 6-month acquisitions in the EX group, showing an area under the ROC curves of 0.887 (95% CI 0.869-0.922). CONCLUSION: Fractal ratio at 6 months can predict exudation risk of MNV within 2 years from diagnosis. This suggests increased structural complexity of the NE-MNV accompanied by progressive capillary rarefaction of the perilesional CC as a key driving factor for the development of exudation in NE-MNV.

[Effectiveness and safety of brolucizumab in the treatment of neovascular age-related macular degeneration]. / Effektivnost' i bezopasnost' brolutsizumaba v lechenii neovaskulyarnoi vozrastnoi makulyarnoi degeneratsii.

PURPOSE: This study analyzes the effectiveness and safety of brolucizumab in the treatment of neovascular age-related macular degeneration (nAMD) in real clinical practice. MATERIAL AND METHODS: The study included patients with nAMD who received brolucizumab treatment and evaluated the changes in best-corrected visual acuity (BCVA), central retinal thickness (CRT), macular volume, as well as the number of injections and adverse events. RESULT: The group of previously treated patients included 28 subjects (28 eyes) that were switched to brolucizumab with a loading phase. By 12 months, BCVA changed from 0.43±0.29 to 0.33±0.27 LogMAR (p=0.11), CRT decreased from 281.5±58.2 to 239.9±45.6 µm (p=0.02). The group of previously untreated patients included 29 subjects (29 eyes). By 12 months, BCVA changed from 0.47±0.32 to 0.40±0.30 LogMAR (p=0.09), CRT decreased from 333.2±77.3 to 226.2±49.6 µm (p<0.001). Patients received 6.3±0.7 injections. In this group, baseline choroidal thickness showed a statistically significant correlation with final visual acuity (r=0.54; p<0.05) and CRT (r= -0.5; p<0.05). The group of previously treated patients switched without a loading phase included 18 patients (18 eyes). By 6 months, BCVA changed from 0.42±0.2 to 0.37±0.26 LogMAR (p=0.42). CRT remained stable at 285.6±56.9 µm (p=0.97). No adverse events related to intraocular inflammation were reported during the course of 385 injections. CONCLUSION: Brolucizumab therapy helps achieve significant anatomical and functional improvements in real clinical practice both in patients switched from previous treatments and in treatment-naïve patients. Greater baseline choroidal thickness may be associated with better anatomical and functional outcomes with brolucizumab treatment.

Retinal vasculitis after intravitreal aflibercept 8 mg for neovascular age-related macular degeneration.

PURPOSE: To evaluate short-term outcomes of intravitreal injection of aflibercept 8 mg for neovascular age-related macular degeneration (nAMD). STUDY DESIGN: Retrospective, interventional case series. METHODS: We retrospectively studied 35 eyes of 34 consecutive patients with nAMD, assessing best-corrected visual acuity (BCVA), foveal thickness (FT), and central choroidal thickness (CCT) before and 4 weeks after the initial intravitreal dose of aflibercept 8 mg. The rate of achieving a dry macula and the incidence of intraocular inflammation (IOI) at week 4 were also determined. RESULTS: BCVA showed significant improvement, with significant reductions in FT and CCT 4 weeks after the initial injection of aflibercept 8 mg (all P < 0.01), with a dry macula being achieved in 20 eyes (57.1%). However, 3 eyes (8.6%) developed non-infectious IOI associated with retinal vasculitis, an adverse event not reported previously. The IOI in these eyes was relatively mild and treated with a posterior subtenon injection of triamcinolone acetonide with or without betamethasone eye drops, resulting in amelioration of IOI without any visual loss. CONCLUSIONS: Intravitreal aflibercept 8 mg appears to be effective for improving visual acuity and ameliorating exudative changes in eyes with nAMD. However, special attention should be given to the potential development of IOI associated with retinal vasculitis.

Long-Term Impact of Diabetic Retinopathy on Response to Anti-VEGF Treatment in Neovascular AMD.

Purpose: To explore the long-term effect of diabetic retinopathy on response to anti-vascular endothelial growth factor (VEGF) treatment in age-related macular degeneration-associated type 1 macular neovascularization (MNV) using optical coherence tomography angiography (OCTA). Methods: A total of 45 eyes with exudative neovascular age-related macular degeneration (nAMD) with type 1 MNV were included in the analysis. Among them, 24 eyes of 24 patients had no history of diabetes mellitus (DM) in their anamnesis and were assigned to the Not Diabetic group; 21 eyes of 21 patients had mild diabetic retinopathy and were included in the Diabetic group. We considered the following outcome measures: (1) best-corrected visual acuity changes; (2) central macular thickness; (3) MNV lesion area; and (4) MNV flow area. The OCTA acquisitions were performed at the following time points: (1) baseline visit, which corresponded to the day before the first injection; (2) post-loading phase (LP), which was scheduled at 1 month after the last LP injection; and (3) 12-month follow-up visit. Results: All morphofunctional parameters showed a significant improvement after the LP and at the 12-month follow-up visit. Specifically, both the Diabetic group and the Not Diabetic group displayed a significant reduction of MNV lesion areas at both the post-LP assessment (P = 0.026 and P = 0.016, respectively) and the 12-month follow-up (P = 0.039 and P = 0.025, respectively). Similarly, the MNV flow area was significantly decreased in both the Diabetic group and the Not Diabetic group at the post-LP assessment (P < 0.001 and P = 0.012, respectively) and at the 12-month follow-up (P = 0.01 and P = 0.035, respectively) compared to baseline. A smaller reduction in the MNV lesion area was observed in the Diabetic group at both the post-LP evaluation (P = 0.015) and the 12-month follow-up (P = 0.032). No other significant differences were found between the groups for the other parameters (P > 0.05). Conclusions: Our results indicated that the Diabetic group exhibited a smaller reduction in MNV lesion area after 12 months of anti-VEGF treatment. This highlights the importance of considering diabetic retinopathy as a potential modifier of treatment outcomes in nAMD management, with DM serving as a crucial risk factor during anti-angiogenic treatment.

Two-year Outcomes of Intravitreal Aflibercept Injection for Neovascular Age-related Macular Degeneration with "Observe before Treat-and-Extend" Method.

PURPOSE: To evaluate 2-year outcomes of intravitreal aflibercept injection for neovascular age-related macular degeneration (nAMD) treated with "observe before treat-and-extend (O-TAE)" strategy in the real-world setting. METHODS: This retrospective study included treatment-naive nAMD patients treated with aflibercept using O-TAE regimen and followed up for more than 2 years. Patients were observed bimonthly to check recurrence after three monthly loading injections. In case of recurrence, treatment was resumed using the TAE regimen starting from the fourth injection. In case of nonrecurrence, observation was continued. Best-corrected visual acuity (BCVA), central macular thickness (CMT), number of injections, TAE intervals, and proportion of recurrence after dry-up following three loadings were analyzed. RESULTS: A total of 38 eyes of 34 patients were included. Follow-up period was 37.0 ± 11.0 months. BCVA by logarithm of minimal angle of resolution improved from 0.33 ± 0.29 at baseline to 0.24 ± 0.23 in the first year (p = 0.010) and 0.25 ± 0.22 in the second year (p = 0.054). CMT decreased significantly from 357.43 ± 74.53 µm at baseline to 269.62 ± 48.12 µm in the first year (p < 0.001) and 279.14 ± 54.64 µm in the second year (p < 0.001). Number of injections were 5.11 ± 1.69 in the first year and 3.84 ± 2.39 in the second year. The percentage of eyes with a TAE interval of ≥12 weeks was 37.0% in the first year and 34.4% in the second year. Of the 36 eyes that dried up after three loadings, 28 eyes (77.8%) recurred, and the average period of recurrence was 6.5 months. The remaining eight eyes (22.2%) had no recurrence during the mean follow-up period of 29.7 months. CONCLUSIONS: This study showed that the newly suggested O-TAE strategy can reduce the treatment burden significantly reducing the number of injections while improving BCVA and CMT in the first and second year.

ARTIFICIAL INTELLIGENCE-ENHANCED ANALYSIS OF RETINAL VASCULATURE IN AGE-RELATED MACULAR DEGENERATION.

PURPOSE: To investigate associations between quantitative vascular measurements derived from intravenous fluorescein angiography (IVFA) and baseline characteristics on optical coherence tomography (OCT) in neovascular age-related macular degeneration (nAMD) patients. METHODS: The authors prospectively recruited patients with active choroidal neovascularization secondary to AMD over 50 years old, presenting to a single center in Toronto, Canada from 2017 to 2023. Ultra-widefield IVFA images were processed using the artificial intelligence RETICAD FAassist system to extract quantitative information on blood flow, perfusion, and blood-retinal-barrier (BRB) permeability. Associations between IVFA parameters with functional and anatomical outcomes were examined using univariable and multivariable regression models. RESULTS: Eighty-one nAMD eyes and seven healthy control eyes were included. Compared with healthy controls, BRB permeability in the central and peripheral retina was significantly higher in nAMD patients (P < 0.001). On univariable analysis, BRB permeability measured centrally was significantly associated with central macular thickness (P = 0.035), whereas perfusion and blood flow measured centrally were significantly associated with macular volume (P = 0.043 and 0.037, respectively). On multivariable analysis, BRB permeability remained significantly associated with central macular thickness (P = 0.026). CONCLUSION: Central BRB permeability measured on IVFA was significantly associated with baseline central macular thickness in nAMD patients. Future work should longitudinally explore associations between IVFA parameters and clinical characteristics in diverse nAMD populations.

INTRAVITREAL ANTI-VASCULAR ENDOTHELIAL GROWTH FACTOR TREATMENT IN PATIENTS WITH NEOVASCULAR AGE-RELATED MACULAR DEGENERATION AND POOR VISUAL ACUITY.

PURPOSE: To investigate the significance of intravitreal anti-vascular endothelial growth factor treatment in patients with neovascular age-related macular degeneration and poor visual acuity. METHODS: Retrospective study of patients with neovascular age-related macular degeneration with baseline best-corrected visual acuity of ≤20/200. Patients were divided into regular treatment and scarce treatment groups according to whether they underwent consecutive intravitreal anti-vascular endothelial growth factor treatments at intervals of ≤4 months or not. RESULTS: A total of 131 eyes were included: 87 and 44 eyes in the regular treatment and scarce treatment groups, respectively. The regular treatment group showed significantly improved preservation of lesion size at both Years 1 and 2, with significantly fewer incidences of new subretinal hemorrhage. Improvements in visual acuity, reduction in central subfield macular thickness, and maximal height of choroidal neovascularization were significantly favorable in the regular treatment group at Year 1, and central subfield macular thickness was significantly decreased at Year 2. Survival analysis revealed that the regular treatment group had significantly greater preservation of visual acuity and lesion size than that in the scarce treatment group. CONCLUSION: Maintaining intravitreal anti-vascular endothelial growth factor treatment for patients with neovascular age-related macular degeneration and poor vision showed significant advantages in visual acuity and lesion size stability and reduced the incidence of new subretinal hemorrhage, which suggests preservation of paracentral vision.

Health-related quality of life in patients with neovascular age-related macular degeneration: a prospective cohort study.

BACKGROUND: Neovascular age-related macular degeneration (nAMD) is a common cause of visual impairment and blindness in the elderly with globally increasing prevalence. Vascular endothelial growth factor inhibitor (anti-VEGF) treatment has improved visual prognosis of nAMD, but continuous treatment may cause anxiety and stress, although increase in visual acuity (VA) may also have positive effects on patients' quality of life. The health care burden due to frequent treatment and monitoring is apparent, but the effect of anti-VEGF treatment on patients' quality of life is not fully understood. We evaluated the overall impact of nAMD and its treatment on newly diagnosed patients' health-related quality of life (HRQoL) in real-world setting. METHODS: The present prospective cohort study included newly diagnosed nAMD patients treated with anti-VEGF injections at Oulu University Hospital during 2019-2020. Data included parameters from comprehensive ophthalmic examination and fundus imaging, age at diagnosis, sex, comorbidities, visual acuity, and frequency of anti-VEGF injections. HRQoL was assessed by 15D questionnaire at diagnosis, 6 months, and 12 months. RESULTS: 95 nAMD patients were included. They were 78 ± 8 years old, 56 (59%) were female, and 74 (78%) had more than one comorbidity. The patients received 8 ± 3 anti-VEGF-injections. Visual acuity (VA) improved from 56 ± 18 to 61 ± 24 Early treatment diabetic retinopathy study (ETDRS) letters in 12 months. VA improved > 5 ETDRS letters in 45 (47%), remained stable in 30 (32%) and decreased > 5 letters in 17 (18%) eyes. The mean total 15D score reflecting overall HRQoL decreased from 0.850 ± 0.104 to 0.834 ± 0.103 in 12 months. Decreased HRQoL was associated with baseline best-corrected VA (BCVA) ≥ 70 ETDRS letters (p = 0.023) and more than one comorbidity (p = 0.034). HRQoL regarding visual function increased from 0.765 ± 0.194 to 0.789 ± 0.184 during the 12-month follow-up. CONCLUSIONS: In real world setting, HRQoL regarding visual function improved in anti-VEGF-treated nAMD patients during the first 12 months after the diagnosis and treatment initiation. Good baseline VA or several comorbidities were associated with decreased overall HRQoL during the follow-up. Despite the effectiveness of anti-VEGF treatment on visual function, several other aspects affecting elderly patients' everyday life should be considered when nAMD treatment is implemented.

The effect of four loading intravitreal aflibercept injections on macular fluid in treatment-naïve neovascular age-related macular degeneration.

PURPOSE: To evaluate the effect of four versus three loading aflibercept injections on macular fluid resolution and visual acuity (VA) in exudative neovascular AMD (nAMD). METHODS: Multicentre, retrospective cohort study of treatment naïve nAMD eyes undergoing 3 versus 4 loading doses of aflibercept. Change in VA and fluid resolution on optical coherence tomography (OCT), were evaluated at 8 weeks post loading. The primary outcome was proportion of patients with no intraretinal (IRF) and/or subretinal (SRF) fluid at central 1 mm and whole macula at 8 weeks after loading. Data were summarised with mean ± SD for continuous variables, and n (%) for categorical variables. RESULTS: Data from 995 patients was analysed (355 patients - 4 loading doses and 640-3 loading doses). At 8 weeks post 4 loading doses proportion of eyes with neither IRF nor SRF, no IRF and no SRF were 62.8%, 88.7% and 79.2% at fovea versus 56.1%, 87.9% and 69.9% in the whole macula, respectively. Fluid resolution at both fovea and macula were significantly higher in eyes with 4 loading injections versus 3 (p = 0.0001). The mean VA change was +4.0 (±11.3) and +5.4(±13.3) letters for 3 and 4 loading doses groups (p = 0.09). CONCLUSION: Four loading dose injections of aflibercept results in higher proportion of eyes with total fluid resolution in the central subfield and total macular scan when compared to those receiving 3 loading dose injections at 8 weeks post loading phase. However, the better drying effect of 4th loading dose does not translate into better short-term VA outcomes.

Progressive Choriocapillaris Changes on Optical Coherence Tomography Angiography Correlate With Stage Progression in AMD.

Purpose: We investigated the association between inner choroid flow deficit percentage (IC-FD%) using swept-source optical coherence tomography angiography (SS-OCTA) and progression of AMD. Methods: Retrospective, observational study including 64 eyes (42 participants) with early or intermediate AMD at baseline. Participants had two or more consecutive swept-source optical coherence tomography angiography covering a period of at least 18 months. Demographics, visual acuity, and AMD staging based on Beckman classification were reviewed. OCT was analyzed for hyperreflective foci, subretinal drusenoid deposits, hyporeflective drusen cores, and subfoveal choroidal thickness. IC-FD% was measured within the central 3- and 6-mm using a 16-µm slab, after compensation and binarization (Phansalkar method). Mixed-effects Cox regression models assessed the association between imaging biomarkers and AMD progression. Results: During follow-up (37 ± 9 months), 4 eyes with early AMD (31%) progressed to intermediate AMD and 30 (59%) eyes with intermediate AMD developed late AMD (19 geographic atrophy; 11 wet AMD). Baseline hyporeflective drusen core was associated with geographic atrophy development (P < 0.01), whereas greater IC-FD% (3-mm) was associated with wet AMD (P = 0.03). Time-varying analysis showed that faster subfoveal choroidal thickness reduction and IC-FD% (6-mm) increase were associated with geographic atrophy onset (P < 0.05), whereas IC-FD% (3-mm) increase was associated with wet AMD (P = 0.03). Notably, greater IC-FD% increases in the 3 mm (area under the curve = 0.72) and 6 mm (area under the curve = 0.89) were better predictive of wet AMD and geographic atrophy development, respectively. Conclusions: Our longitudinal IC-FD% assessment emphasizes the role of progressive choriocapillaris changes as a biomarker for AMD progression. Our findings support that widespread choriocapillaris alterations (6 mm) may precede progression to geographic atrophy, whereas more central choriocapillaris loss (3 mm) may provide an ischemic stimulus for wet AMD.

Role of inflammation in diabetic macular edema and neovascular age-related macular degeneration.

Diabetic macular edema (DME) and neovascular age-related macular degeneration (nAMD) are multifactorial disorders that affect the macula and cause significant vision loss. Although inflammation and neoangiogenesis are hallmarks of DME and nAMD, respectively, they share some biochemical mediators. While inflammation is a trigger for the processes that lead to the development of DME, in nAMD inflammation seems to be the consequence of retinal pigment epithelium and Bruch membrane alterations. These pathophysiologic differences may be the key issue that justifies the difference in treatment strategies. Vascular endothelial growth factor inhibitors have changed the treatment of both diseases, however, many patients with DME fail to achieve the established therapeutic goals. From a clinical perspective, targeting inflammatory pathways with intravitreal corticosteroids has been proven to be effective in patients with DME. On the contrary, the clinical relevance of addressing inflammation in patients with nAMD has not been proven yet. We explore the role and implication of inflammation in the development of nAMD and DME and its therapeutical relevance.

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

OBJECTIVE: To 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 ANALYSIS: A systematic review (SR) was conducted up to January 2023. Network meta-analyses (NMA) were performed, including sensitivity and subgroup analyses for naïve population. Outcomes included changes in visual acuity (Early Treatment of Diabetic Retinopathy Study [ETDRS] letters), anatomical changes, frequency of injections and adverse events. The Cochrane Collaboration guidelines and the Confidence in Network Meta-Analysis framework were used for the SR and the certainty of evidence, respectively. RESULTS: From 4128 identified records through electronic databases and complementary searches, 63 randomised controlled trials (RCTs) met the eligibility criteria, with 42 included in the NMA. Faricimab showed a significant reduction in the number of annual injections compared with most fixed and flexible anti-VEGF treatment regimens, while showing no statistically significant differences in visual acuity through ETDRS letter gain, demonstrating a comparable efficacy. Retinal thickness results showed comparable efficacy to other anti-VEGF agents, and inferior only to brolucizumab. Results also showed that more patients treated with faricimab were free from post-treatment retinal fluid compared with aflibercept every 8 weeks, and both ranibizumab and bevacizumab, in the fixed and pro re nata (PRN) assessed schedules. Faricimab showed a comparable safety profile regarding the risk of ocular adverse events and serious ocular adverse events (SOAE), except for the comparison with brolucizumab quarterly, in which faricimab showed a significant reduction for SOAE risk. CONCLUSION: Faricimab showed a comparable clinical benefit in efficacy and safety outcomes, with a reduction in annual injections compared with fixed and flexible anti-VEGF drug regimens, representing a valuable treatment option for nAMD patients. PROSPERO REGISTRATION NUMBER: CRD42023394226.

Factors affecting prognosis and need for anti-vascular endothelial growth factor injections in wet age-related macular degeneration.

PURPOSE: To understand factors affecting visual prognosis and the number of intravitreal antivascular endothelial growth factor (anti-VEGF) injections needed to stabilize wet age-related macular degeneration (AMD). METHODS: In this retrospective cohort, 119 treatment-naïve wet AMD patients were followed for two years. In patients with bilateral disease, the eye with worse best-corrected visual acuity (BCVA) or that received more intravitreal injections was recruited as the study eye. In all visits, BCVA was recorded, ophthalmological examination was performed including macular optical coherence tomography imaging. Twenty health status/lifestyle questions were asked to the patients via phone as potential risk factors. All patients received 3 loading doses of intravitreal bevacizumab injections and received repeat injections of aflibercept or ranibizumab when the eye had a new, active neovascular lesion. RESULTS: Patients who took regular micronutrition had similar visual outcome and injection numbers compared to the ones who did not. Patients with bilateral disease needed less intravitreal injections compared to unilateral AMD patients (p = 0.016) and women on hormone replacement therapy (HRT) required less injections compared to the women who were not (p = 0.024). Female patients had a mean gain of 2.7 letters while male patients lost 3.8 letters (p = 0.038). Wet AMD started at an earlier age in smokers (p = 0.002). Patients with a better education level presented earlier with better BCVA (p = 0.037). CONCLUSION: HRT and anti-VEGF injections to the fellow eye improved the prognosis of wet AMD, while male patients had slightly worse prognosis. Estrogen's protective effects and potential contribution in wet AMD needs further attention. Retrospectively registered: 2020/0622.