Long-term Follow-Up and Regeneration of Retinal Pigment Epithelium (RPE) after Tears of the Epithelium in Exudative Age-Related Macular Degeneration (AMD).

BACKGROUND: The goals of this study are to evaluate potential long-term visual deterioration associated with retinal pigment epithelial (RPE) tears in patients with neovascular age-related macular degeneration (nAMD) and to find treatment-related and morphological factors that might influence the outcomes. PATIENTS AND METHODS: This retrospective study enrolled 21 eyes of 21 patients from the database of Vista Eye Clinic Binningen, Switzerland, diagnosed with RPE tears, as confirmed by spectral domain optical coherence tomography (SD-OCT), with a minimum follow-up period of 12 months. Treatment history before and after RPE rupture with anti-VEGF therapy, visual acuity, and imaging (SD-OCT) were analyzed and statistically evaluated for possible correlations. RESULTS: Mean patient age was 80.5 ± 6.2 years. The mean length of total follow-up was 39.7 ± 13.9 months. The mean pigment epithelial detachment (PED) height increased by 363.8 ± 355.5 µm from the first consultation to 562.8 ± 251.5 µm at the last consultation prior to rupture. Therefore, a higher risk of RPE rupture is implied as a result of an increase in PED height (p = 0.004, n = 14). The mean visual acuity before rupture was 66.2 ± 16.0 letters. Mean visual acuity deteriorated to 60.8 ± 18.6 letters at the first consultation after rupture (p = 0.052, n = 21). A statistically nonsignificant decrease in vision was noted in the follow-up period. After 2 years, the mean BCVA decreased by 10.5 ± 23.7 ETDRS letters (p = 0.23, n = 19). PED characteristics before rupture and amount of anti-VEGF injections after rupture did not affect the visual outcome. None of the 21 patients included in our study showed a visual improvement in the long-term follow-up. RPE atrophy increased significantly from 3.35 ± 2.94 mm2 (baseline) to 6.81 ± 6.25 mm2 over the course of 2 years (p = 0.000 013, n = 20). CONCLUSIONS: The overall mean vision decrease after rupture was without statistical significance. There was no significant change in BCVA at the 2-year follow-up, independent of the amount of anti-VEGF injections provided. In this study, there was a significant increase in RPE defect over a follow-up of 2 years, implying progression of contraction of RPE and/or macular atrophy.

Short-term response to anti-VEGF as indicator of visual prognosis in refractory age-related macular degeneration.

BACKGROUND: Some patients with neovascular age-related macular degeneration (nAMD) respond insufficiently to anti-VEGF treatment despite maximal monthly intravitreal injections. Their short-term response between injections was investigated for extent and visual prognosis. SUBJECTS/METHODS: Monocentric retrospective observational study. 45 eyes from 41 patients with refractory nAMD (who previously received at least 12 months of anti-VEGF treatment), evaluated by optical coherence tomography (OCT) in between monthly anti-VEGF injections. The fluid profile on OCT was evaluated before, 1 week after, and 1 month after an intravitreal injection, using central retinal thickness (CRT), manual measurements, and fluid specific volumetric measurements performed by an automated algorithm based on artificial intelligence. RESULTS: A significant improvement was found at week 1 in terms of CRT (p < 0.0001), intraretinal (IRF) (p = 0.007), subretinal fluid (SRF) (p < 0.0001), and pigment epithelium detachment (PED) volume (p < 0.0001). Volumetric fluid measures revealed a >50% reduction at week 1 for both IRF and SRF for approximately two-thirds of eyes. Poorer short-term response was associated with larger exudative fluid amounts (IRF + SRF) (p = 0.003), larger PED (p = 0.007), lower visual acuity (p = 0.004) and less anatomic changes at treatment initiation (p < 0.0001). Univariate and multivariate analysis revealed that visual outcomes 4 and 5 years later was significantly worse with weaker short-term responsiveness (p = 0.005), with the presence of atrophy (p = 0.01) and larger PED volumes (p = 0.002). CONCLUSIONS: Incomplete responders to anti-VEGF showed a significant short-term response, identifiable at 1 week after injection, with rapid recurrence at 1 month. Weaker short-term responsiveness at 1 week was associated with poorer long term visual prognosis. These patients may need adjuvant treatment to improve their prognosis.

Baseline characteristics of eyes with early residual fluid post loading phase of aflibercept therapy in neovascular AMD: PRECISE study report 3.

PURPOSE: To compare the baseline characteristics in patients with and without early residual fluid (ERF) after aflibercept loading phase (LP) in patients with treatment naïve neovascular age related macular degeneration (nAMD). METHODS: Patients with nAMD initiated on LP of three intravitreal aflibercept doses were recruited from December 2019 to August 2021. Baseline demographic and OCT features associated with any ERF were analysed using Generalised Estimating Equations to account for inter-eye correlation. Receiver operating characteristic (ROC) curve was performed for selection of CST threshold. RESULTS: Of 2128 patients enrolled, 1999 eyes of 1862 patients with complete data were included. After LP, ERF was present in 1000 (50.0%), eSRF in 746(37.3%) and eIRF in 428 (21.4%) eyes. In multivariable analysis of baseline features, eyes with increased central subfield thickness (CST) (OR 1.31 per 100 microns increase [95% CI 1.22 to 1.41]; P < 0.001), eyes with IRF and SRF at baseline (1.62 [95% CI 1.17 to 2.22]; P = 0.003), and those with SRF only (OR 2.26 [95% CI 1.59 to 3.20]; P < 0.001) relative to IRF only were determinants of ERF. CST ≥ 418 microns had 57% sensitivity and 58% specificity to distinguish ERF from no ERF at visit 4. CONCLUSION: On average, 50% of eyes have ERF after aflibercept LP. Clinically relevant baseline determinants of ERF include CST ≥ 418 µ and presence of only SRF. These eyes may require further monthly treatment before extending treatment intervals.

MORPHOLOGIC AND ANATOMICAL FEATURES OF TYPE 1 MACULAR NEOVASCULARIZATION TRUNKS IN AGE-RELATED MACULAR DEGENERATION USING OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY.

PURPOSE: To evaluate the morphologic features of macular neovascularization (MNV) trunks at different layers using optical coherence tomography angiography. METHODS: Type 1 MNV trunks in age-related macular degeneration were retrospectively evaluated at the subretinal pigment epithelium and sub-Bruch membrane (subBM) layers. The detectability and location of the trunks were compared. MNV trunks at the subBM layer on optical coherence tomography angiography B-scans were evaluated using a flow overlay. The correlations of the MNV trunk with optical coherence tomography angiography and optical coherence tomography parameters were evaluated. RESULTS: Among the 63 included eyes, 27 showed core vessels at the subretinal pigment epithelium layer and 52 showed MNV trunks at the subBM layer, which were connected with the MNV at the subretinal pigment epithelium layer. The locations of the MNV trunks in each layer were different. MNV trunk types at the subBM layer were related to disease duration, distance from the large choroidal vessels, and MNV vessel density. The large choroidal vessel diameter was correlated with the MNV trunk diameter at the subBM layer. CONCLUSION: Macular neovascularization trunks at the subBM layer were detected more frequently than distal MNV trunks at the subretinal pigment epithelium layer. Macular neovascularization trunk features at the subBM layer may be related to disease duration and a large choroidal vessel.

Archway Randomized Phase 3 Trial of the Port Delivery System with Ranibizumab for Neovascular Age-Related Macular Degeneration.

PURPOSE: To evaluate the safety and efficacy of the Port Delivery System with ranibizumab (PDS) for the treatment of neovascular age-related macular degeneration (nAMD). DESIGN: Phase 3, open-label, randomized, visual acuity assessor-masked noninferiority and equivalence trial. PARTICIPANTS: Patients with nAMD diagnosed within 9 months of screening previously treated with and responsive to anti-vascular endothelial growth factor therapy. METHODS: Patients were randomized 3:2 to treatment with the PDS with ranibizumab 100 mg/ml with fixed 24-week (Q24W) refill-exchanges (PDS Q24W) or intravitreal ranibizumab 0.5-mg injections every 4 weeks (monthly ranibizumab). MAIN OUTCOME MEASURES: Primary end point was change in best-corrected visual acuity (BCVA) Early Treatment Diabetic Retinopathy Study letter (letters) score from baseline averaged over weeks 36 and 40 (noninferiority margin,-4.5 letters; equivalence margin, ±4.5 letters). RESULTS: Archway enrolled 418 patients; 251 were randomized to and 248 received treatment with the PDS Q24W, and 167 were randomized to and received treatment with monthly ranibizumab. Baseline BCVA was 74.4 letters (PDS Q24W arm) and 75.5 letters (monthly ranibizumab arm; Snellen equivalent, 20/32). Adjusted mean change in BCVA score from baseline averaged over weeks 36 and 40 was +0.2 letters (standard error [SE], 0.5 letters) in the PDS Q24W arm and +0.5 letters (SE, 0.6 letters) in the monthly ranibizumab arm (difference, -0.3 letters; 95% confidence interval, -1.7 to 1.1 letters). PDS Q24W was both noninferior and equivalent to monthly ranibizumab. Of 246 PDS-treated patients assessed for supplemental ranibizumab treatment, 242 (98.4%) did not receive supplemental ranibizumab treatment before the first refill-exchange procedure, including 4 patients who discontinued treatment before the first refill-exchange procedure. Prespecified ocular adverse events of special interest were reported in 47 patients (19.0%) in the PDS Q24W arm and 10 patients (6.0%) in the monthly ranibizumab arm, which included, in the former arm, 4 (1.6%) endophthalmitis cases, 2 (0.8%) retinal detachments, 13 (5.2%) vitreous hemorrhages, 6 (2.4%) conjunctival erosions, and 5 (2.0%) conjunctival retractions. Most ocular adverse events in the PDS Q24W arm occurred within 1 month of implantation. CONCLUSIONS: Archway met its primary objective and PDS Q24W demonstrated noninferior and equivalent efficacy to monthly ranibizumab, with 98.4% of PDS-treated patients not receiving supplemental treatment in the first 24-week interval.

Efficacy and Safety of Biosimilar FYB201 Compared with Ranibizumab in Neovascular Age-Related Macular Degeneration.

PURPOSE: This trial was conducted to investigate the clinical equivalence of the proposed biosimilar FYB201 and reference ranibizumab in patients with treatment-naive, subfoveal choroidal neovascularization caused by neovascular age-related macular degeneration (nAMD). DESIGN: This was a prospective, multicenter, evaluation-masked, parallel-group, 48-week, phase III randomized study. PARTICIPANTS: A total of 477 patients were randomly assigned to receive FYB201 (n = 238) or reference ranibizumab (n = 239). METHODS: Patients received FYB201 or reference ranibizumab 0.5 mg by intravitreal (IVT) injection in the study eye every 4 weeks. MAIN OUTCOME MEASURES: The primary end point was change from baseline in best-corrected visual acuity (BCVA) by Early Treatment Diabetic Retinopathy Study (ETDRS) letters at 8 weeks before the third monthly IVT injection. Biosimilarity of FYB201 to its originator was assessed via a 2-sided equivalence test, with an equivalence margin in BCVA of 3 ETDRS letters. RESULTS: The BCVA improved in both groups, with a mean improvement of +5.1 (FYB201) and +5.6 (reference ranibizumab) ETDRS letters at week 8. The analysis of covariance (ANCOVA) least squares mean difference for the change from baseline between FYB201 and reference ranibizumab was -0.4 ETDRS letters with a 90% confidence interval (CI) of -1.6 to 0.9. Primary end point was met as the 90% CI was within the predefined equivalence margin. Adverse events were comparable between treatment groups. CONCLUSIONS: FYB201 is biosimilar to reference ranibizumab in terms of clinical efficacy and ocular and systemic safety in the treatment of patients with nAMD.

EFFECT OF RETINAL THICKNESS VARIABILITY ON VISUAL OUTCOMES AND FLUID PERSISTENCE IN NEOVASCULAR AGE-RELATED MACULAR DEGENERATION: A Post Hoc Analysis of the HAWK and HARRIER Studies.

PURPOSE: To determine the association between central subfield thickness (CST) variability and visual outcomes in eyes with neovascular age-related macular degeneration treated with anti-vascular endothelial growth factor therapies. METHODS: In this post hoc, treatment-agnostic analysis, patients (N = 1,752) were grouped into quartiles of increasing CST variation. The association between CST variability and best-corrected visual acuity was measured from baseline, or from the end of the loading phase, until the end of the study using a multilevel modeling for repeated-measures model. The association between CST variability and the presence of retinal fluid was also assessed. RESULTS: Increased CST variability was associated with worse best-corrected visual acuity outcomes at the end of study, with a least-square mean difference in best-corrected visual acuity of 8.9 Early Treatment Diabetic Retinopathy Study letters between the quartiles with the lowest and highest CST variability at the final visit. Increased variability was also associated with a higher mean fraction of visits with the presence of fluid. CONCLUSION: More stable CST was associated with better visual outcomes at the end of treatment suggesting that CST variability may provide a more reliable prognostic marker of visual outcomes than the presence of fluid alone, with the potential to enhance the clinical care of neovascular age-related macular degeneration patients.

CHOROIDAL IMAGING BIOMARKERS TO PREDICT HIGHLY RESPONSIVE AND RESISTANT CASES TREATED WITH STANDARDIZED ANTI-VASCULAR ENDOTHELIAL GROWTH FACTOR REGIMEN IN NEOVASCULAR AGE-RELATED MACULAR DEGENERATION.

PURPOSE: To determine structural predictors of treatment response in neovascular age-related macular degeneration analyzing optical coherence tomography (OCT)-related biomarkers. METHODS: A retrospective review of patients undergoing treatment for neovascular age-related macular degeneration at a tertiary institute was performed at presentation. High-intensity regimen included eyes on long-term anti-vascular endothelial growth factor treatment with the inability to extend beyond a month without a relapse and needed double the dose of medication (n = 25). Low-intensity regimen had eyes that went into long-term remission after at least three injections and remained dry for more than a year until the last visit (n = 20). Multimodal imaging including fluorescein angiogram, OCT, and comprehensive ocular evaluation were done. Choroidal vascularity index, total choroidal area, luminal area, subfoveal choroidal thickness, choriocapillaris thickness and Haller and Sattler layer thickness were analyzed for statistical significance. RESULTS: The groups had no significant difference at baseline in age, gender, incidence of reticular pseudodrusen, polypoidal choroidal vasculopathy feature on OCT, type of choroidal neovascular membrane, and geographic atrophy. Multinomial logistic regression revealed that thicker subfoveal choroidal thickness and larger total choroidal area were the significant predictors of poor response to anti-vascular endothelial growth factor treatment (E = 0.02; P = 0.02; E = 1.82; P = 0.0075). CONCLUSION: Thicker subfoveal choroidal thickness and higher total choroidal area are useful variables to predict a poor treatment response.

MACULAR HOLE ASSOCIATED WITH AGE-RELATED MACULAR DEGENERATION: Pathogenesis and Surgical Outcomes.

PURPOSE: To ascertain the pathogenesis of macular hole (MH) associated with age-related macular degeneration (AMD) and its surgical outcomes. METHODS: Patients with full-thickness MH associated with AMD (higher grades than intermediate) were enrolled. The mechanism of MH formation and closure rate after vitrectomy (surgical outcome) were determined using optical coherence tomography imaging. RESULTS: The mechanism of MH formation (35 eyes) associated with AMD was classified into four types: vitreomacular traction (42.9%), gradual retinal thinning caused by subretinal drusen or pigment epithelial detachment (22.9%), massive subretinal hemorrhage (20.0%), and combined (14.3%). In the 41 eyes that underwent vitrectomy, the logarithm of the minimum angle of resolution best-corrected visual acuity improved from 0.82 (0.10-2.30) preoperative to 0.69 (0.10-2.30) postoperative (P = 0.001). Successful closure of the MH was achieved in 33 eyes (80.5%) after vitrectomy. No significant association was observed between the closure rate of MH after vitrectomy and mechanism of MH formation (P = 0.083). CONCLUSION: The mechanism of MH formation associated with AMD was classified into four types and was not related to its surgical outcome. Considering visual improvement and surgical outcome after vitrectomy in our study, active surgical treatment can be considered for MH associated with AMD.

OUTCOMES IN PATIENTS RESUMING INTRAVITREAL ANTI-VASCULAR ENDOTHELIAL GROWTH FACTOR THERAPY FOLLOWING TREATMENT DELAY DURING THE CORONAVIRUS-19 PANDEMIC.

PURPOSE: To evaluate the outcomes of delay in care secondary to the coronavirus pandemic in patients requiring intravitreal anti-vascular endothelial growth factor therapy. METHODS: A retrospective review was performed, and subjects were divided into two groups: 1) a study group of patients who experienced a treatment delay of ≥6 weeks from the intended follow-up during the coronavirus pandemic and resumed treatment with ≥2 anti-vascular endothelial growth factor injections over 6 months following treatment delay, and 2) a control group of patients who received regular care throughout the coronavirus pandemic. RESULTS: Totally, 234 subjects were analyzed. The mean treatment delay from the intended follow-up in the study group was 11.8 (±4.0) weeks. Visual acuity and central macular thickness worsened from baseline to 6 months after resuming anti-vascular endothelial growth factor therapy in the study group (P < 0.0001 and P = 0.001, respectively). Visual acuity and central macular thickness were better in the control group compared with the study group at the end of the 6-month study period (P < 0.0001 for both). CONCLUSION: Treatment delay in subjects undergoing anti-vascular endothelial growth factor therapy for retina disease during the coronavirus pandemic had worse visual and anatomical outcomes despite reinitiating treatment over 6 months compared with a control group, suggesting irreversibility and permanence of outcomes.

Hyperreflective Foci, Optical Coherence Tomography Progression Indicators in Age-Related Macular Degeneration, Include Transdifferentiated Retinal Pigment Epithelium.

Purpose: By optical coherence tomography (OCT) imaging, hyperreflective foci (HRF) indicate progression risk for advanced age-related macular degeneration (AMD) and are in part attributable to ectopic retinal pigment epithelium (RPE). We hypothesized that ectopic RPE are molecularly distinct from in-layer cells and that their cross-retinal course follows Müller glia. Methods: In clinical OCT (61 eyes, 44 patients with AMD, 79.4 ± 7.7 years; 29 female; follow-up = 4.7 ± 0.9 years), one HRF type, RPE plume (n = 129 in 4 morphologies), was reviewed. Twenty eyes of 20 donors characterized by ex vivo OCT were analyzed by histology (normal, 4; early/intermediate AMD, 7; geographic atrophy, 6; neovascular AMD, 3). Cryosections were stained with antibodies to retinoid (RPE65, CRALPB) and immune (CD68, CD163) markers. In published RPE cellular phenotypes, red immunoreactivity was assessed semiquantitatively by one observer (none, some cells, all cells). Results: Plume morphology evolved over time and many resolved (40%). Trajectories of RPE plume and cellular debris paralleled Müller glia, including near atrophy borders. RPE corresponding to HRF lost immunoreactivity for retinoid markers and gained immunoreactivity for immune markers. Aberrant immunoreactivity appeared in individual in-layer RPE cells and extended to all abnormal phenotypes. Müller glia remained CRALBP positive. Plume cells approached and contacted retinal capillaries. Conclusions: HRF are indicators not predictors of overall disease activity. Gain and loss of function starts with individual in-layer RPE cells and extends to all abnormal phenotypes. Evidence for RPE transdifferentiation, possibly due to ischemia, supports a proposed process of epithelial-mesenchyme transition. Data can propel new biomarkers and therapeutic strategies for AMD.

Diagnostic Accuracy of Monitoring Tests of Fellow Eyes in Patients with Unilateral Neovascular Age-Related Macular Degeneration: Early Detection of Neovascular Age-Related Macular Degeneration Study.

PURPOSE: To evaluate the diagnostic accuracy of routinely used tests of visual function and retinal morphology compared with fundus fluorescein angiography (FFA) to detect onset of active macular neovascularization in unaffected fellow eyes of patients with unilateral neovascular age-related macular degeneration (nAMD). DESIGN: Prospective diagnostic accuracy cohort study conducted in 24 eye clinics in the United Kingdom over 3 years. PARTICIPANTS: Older adults (>50 years) with recently diagnosed unilateral nAMD with a fellow (study) eye free of nAMD. METHODS: Self-reported vision, Amsler, clinic-measured visual acuity (VA), fundus assessment, and spectral domain OCT. The reference standard is FFA. MAIN OUTCOME MEASURES: Sensitivity and specificity of the 5 index tests. RESULTS: Of 552 participants monitored for up to 3 years, 145 (26.3%) developed active nAMD in the study eye, of whom 120 had an FFA at detection and constituted the primary analysis cohort. Index test positives at nAMD detection in those confirmed by FFA were self-reported vision much worse (5), distortion on Amsler (33), 10-letter decrease in acuity from baseline (36), fundus examination (64), and OCT (110). Percentage index test sensitivities were: self-reported vision 4.2 (95% confidence interval [CI], 1.6-9.8); Amsler 33.7 (95% CI, 25.1-43.5); VA 30.0 (95% CI, 22.5-38.7); fundus examination 53.8 (95% CI, 44.8-62.5); and OCT 91.7 (95% CI, 85.2-95.6). All 5 index test specificities were high at 97.0 (95% CI, 94.6-98.5), 81.4 (95% CI, 76.4-85.5), 66.3 (95% CI, 61.0-71.1), 97.6 (95% CI, 95.3-98.9), and 87.8 (95% CI, 83.8-90.9), respectively. The combination of OCT with one other index test that was a secondary outcome measure increased sensitivity marginally and decreased specificity for all combinations except fundus examination. CONCLUSIONS: Tests of self-reported change in vision, unmasking of new distortion, measurements of acuity, and fundus checks to diagnose active nAMD performed poorly in contrast to OCT. Our findings support a change to guidelines in clinical practice to monitor for onset of nAMD.

Altered serum levels of autophagy proteins Beclin-1 and mTOR in patients with exudative age-related macular degeneration.

Autophagy is a key process in the maintenance of cellular survival and homeostasis. Inhibition of autophagy results in degenerative changes resembling ageing. We wondered if autophagy can contribute to the pathogenesis of age-related macular degeneration (AMD). We aimed to investigate the serum concentrations of two key autophagy regulators, Beclin-1 and mechanistic target of rapamycin (mTOR), in patients with exudative AMD. This retrospective case-control study included 38 patients with exudative AMD and 36 sex- and age-matched controls selected among senile cataract patients. Circulating Beclin-1 and mTOR were assessed using an enzyme-linked immunosorbent assay. The proteins levels were correlated with age, sex, duration of ocular symptoms, as well as angiographic and optical coherence tomography findings. Serum Beclin-1 levels were much lower in patients with AMD than in controls (median, 0.100 ng/ml versus 1.123 ng/ml; p = 0.0033), while mTOR levels did not differ (median, 4.377 ng/ml versus 3.608 ng/ml; p = 0.4522). Participants of the study older than 70 years had lower Beclin-1 levels than younger ones (p = 0.0444). However, this difference was the most evident in patients with AMD (p = 0.0024). Serum mTOR levels increased with age. In patients with AMD, lower mTOR levels were associated with drusen, while higher levels were observed in those with a fibrous scar in the contralateral eye (p = 0.0212). Our findings suggest that circulating Beclin-1 decreases with age and that is downregulated in patients with AMD.

Cytokine and Chemokine Profile Changes in Patients with Neovascular Age-Related Macular Degeneration After Intravitreal Ranibizumab Injection for Choroidal Neovascularization.

OBJECTIVE: To investigate the concentrations of cytokine and chemokines profiling in aqueous humor for choroidal neovascularization (CNV) due to neovascular age-related macular degeneration (nAMD) before and during Intravitreal injection of ranibizumab (IVR) and its relation with the disease's active state. METHODS: The cytokine levels in aqueous humour were detected by the Bio-Plex® 200 System and the Bio-Plex™ Human Cytokine Standard 27-Plex, Group I. Aqueous humour samples of experimental group were collected from 19 patients diagnosed nAMD at baseline and at 1 month after IVR. Aqueous humour samples of control group were collected from 20 patients undergoing cataract surgery. RESULTS: Aqueous humor levels of basic fibroblast growth factor (basic FGF) and RANTES were significantly lower in nAMD patients than in the control group (P=0.044 and P<0.001, respectively). Vascular endothelial growth factor-A (VEGF-A) was significantly higher in nAMD patients than in the control group (P < 0.001). The average Eotaxin levels were significantly higher in nAMD patients after IVR than before (P=0.03). Contrarily, the average VEGF-A levels were significantly lower in AMD patients after IVR than before (P < 0.001). CONCLUSION: Angiogenic, growth factors and inflammatory are involved in the formation of neovascularization of AMD patients. IVR did not cause significant differences in any growth factors or inflammatory cytokines in nAMD patients with the exception of VEGF.

Aflibercept Treatment Results and Association with Baseline Characteristics in Cases of Newly Diagnosed Neovascular Age-Related Macular Degeneration

Objectives: To evaluate functional and anatomical responses to intravitreal aflibercept (IVA) treatment in newly diagnosed and untreated neovascular age-related macular degeneration (nvAMD) cases and to investigate the effect of baseline lesion characteristics on anatomical responses. Materials and Methods: This prospective, cross-sectional study included a series of 139 eyes of 133 patients that were diagnosed with active nvAMD and had not been treated. All eyes were subjected to complete ophthalmological examination, spectral-domain optical coherence tomography and fluorescein angiography, and 42 eyes also underwent indocyanine green angiography. IVA treatment was performed using a "treat and extend" regimen after 3 injections at 4-6 weeks intervals. Anatomical and functional responses at 4 weeks after the last injection were evaluated in eyes that completed 3 injections and the subgroup of eyes that completed 6 IVA injections. The effect of baseline lesion characteristics on IVA treatment results was also investigated. Results: All 139 eyes included in the study received 3 IVA injections (group 1) and 62 received 6 IVA injections. Both groups showed statistically significant improvement in best-corrected visual acuity (p<0.001 for both). The rate of complete response was 54.6% and 58.0% in groups 1 and 2, respectively. In group 1, the presence of pigment epithelial detachment (PED) and serous PED were identified as negative initial factors (p=0.043, p=0.005, respectively). However, none of the baseline characteristics were significantly associated with anatomical response in group 2. Conclusion: In our study, it was determined that successful anatomical and functional results were achieved with 3 and 6 doses of IVA in eyes with newly-diagnosed and untreated nvAMD. Among baseline characteristics, the presence of PED and serous PED in particular were found to be factors affecting treatment response negatively.

Predominantly Persistent Subretinal Fluid in the Comparison of Age-Related Macular Degeneration Treatments Trials.

OBJECTIVE: To describe predominantly persistent subretinal fluid (SRF) in eyes receiving ranibizumab or bevacizumab for neovascular age-related macular degeneration and to compare visual acuity (VA) to eyes with nonpersistent SRF. DESIGN: Cohort within randomized clinical trial. PARTICIPANTS: Comparison of Age-related Macular Degeneration Treatments Trials patients assigned to pro re nata treatment. METHODS: Graders evaluated monthly OCT scans for SRF. Predominantly persistent SRF through week 12 was defined as SRF at baseline and weeks 4, 8, and 12. Predominantly persistent SRF through 1 or 2 years was defined as SRF in 80% or more of visits by years 1 or 2, respectively. Linear regression models including baseline predictors of VA and predominantly persistent intraretinal fluid (IRF) were used to evaluate mean differences in vision outcomes. PRIMARY OUTCOME MEASURES: Predominantly persistent SRF through year 1, adjusted VA score and VA change, and foveal SRF thickness. RESULTS: Among 406 eyes with baseline SRF, SRF persisted in 108 eyes (26.6%) through week 12, in 94 eyes (23.2%) through year 1, and in 77 eyes (19.0%) through year 2. Adjusted VA means at year 1 were similar between eyes with predominantly persistent versus non persistent SRF by week 12 (68.1 vs. 70.2 letters; P = 0.18), year 1 (67.6 vs. 70.2 letters; P = 0.11), and year 2 (71.4 vs. 70.9 letters; P = 0.78). Adjusted changes in mean VA at year 1 were similar between eyes with predominantly persistent versus nonpersistent SRF by week 12 (6.3 vs. 7.6 letters; P = 0.38), year 1 (5.5 vs. 7.8 letters; P = 0.14), and year 2 (8.1 vs. 7.7 letters; P = 0.78). Among eyes with predominantly persistent SRF through year 1, foveal SRF was absent in 46 eyes (48.9%), thickness was 1 to 200 µm in 48 eyes (50.0%) and more than 200 µm in 1 eye (1.1%) at year 1. CONCLUSIONS: Eyes with predominantly persistent and nonpersistent SRF through week 12, year 1, or year 2 showed similar VA outcomes after adjustment for baseline covariates and persistent IRF. At the foveal center, predominantly persistent SRF was most commonly absent or present in small quantities.

LONG-TERM COURSE AND VISUAL OUTCOMES OF PRECHOROIDAL CLEFT IN NEOVASCULAR AGE-RELATED MACULAR DEGENERATION AND POLYPOIDAL CHOROIDAL VASCULOPATHY.

PURPOSE: To evaluate the regression of prechoroidal cleft, its influence on visual outcomes, and differences in visual outcomes between neovascular age-related macular degeneration and polypoidal choroidal vasculopathy. METHODS: This retrospective study included 61 patients exhibiting prechoroidal cleft who were treated with antivascular endothelial growth factors. The patients were divided into two groups according to the following categories: 1) regression of prechoroidal cleft: regression group versus nonregression group and 2) type of neovascularization: neovascular age-related macular degeneration group versus polypoidal choroidal vasculopathy group. Changes in the visual acuity during the follow-up period were also compared between the two groups. RESULTS: During the 52.4 ± 17.4-month follow-up period, regression of prechoroidal cleft was noted in 17 patients (27.9%) at a mean of 25.7 ± 18.3 months after the first identification. The degree of the logarithm of the minimum angle of resolution of visual deterioration was greater in the nonregression group (0.59 ± 0.56, n = 17) than that in the regression group (0.25 ± 0.61, n = 44) (P = 0.007) and in the neovascular age-related macular degeneration group (0.56 ± 0.61, n = 51) than that in the polypoidal choroidal vasculopathy group (0.18 ± 0.33, n = 10) (P = 0.034). CONCLUSION: Approximately 27.9% of prechoroidal cleft cases eventually regressed, in conjunction with relatively favorable visual outcomes. Considering the poor visual prognosis in neovascular age-related macular degeneration accompanied by prechoroidal cleft, more caution is required for this condition.