Comparative Study on Anti-VEGF in Wet Age-Related Macular Degeneration in the Setting Based on Lean Methodology from the Bari Intravitreal Injection Registry (BIVIR).

INTRODUCTION: Optimizing treatment protocols for wet age-related macular degeneration (wAMD) is an ongoing challenge, as it involves a delicate balance between achieving therapeutic efficacy and minimizing invasive procedures' frequency. This study aimed to apply the Lean methodology and evaluate the effectiveness of this new setting on intravitreal therapy for wAMD, employing different anti-vascular endothelial growth factors (VEGF) drugs (bevacizumab, brolucizumab, aflibercept, ranibizumab), drawing data from the Bari Intravitreal Injections Registry (BIVIR). METHODS: This was a retrospective, monocentric, nonrandomized, comparative study. Lean methodology was employed to design the new setting and the BIVIR collected information from electronic medical records. Clinical data of four groups, stratified based on the first-line anti-VEGF agents used, were compared. Best-corrected visual acuity (BCVA) and central retinal thickness (CRT) changes were compared between the four groups at 3 and 12 months. RESULTS: Out of 4990 eyes and 41,323 intravitreal injections (IVs) recorded in BIVIR, 1421 eyes of 1182 patients were included. The mean number of IVs in first year was 6.1 ± 2.5, with no significant differences among the four subgroups. The mean change in BCVA was + 6.2 letters [95% confidence interval (CI) 5.6-6.8] after two IVs, and + 5.9 (95% CI 5.1-6.8) letters after three IVs; at three months, brolucizumab was associated with a greater mean increase in BCVA than bevacizumab (p = 0.050); aflibercept (p = 0.044) and ranibizumab p = 0.047). At the 1-year follow-up, the mean change was + 6.3 letters (95% CI 5.4-7.2), brolucizumab and ranibizumab were associated with a superior improvement in BCVA compared to aflibercept (p = 0.033). Regarding the CRT, a significant reduction was observed in the subgroup treated with brolucizumab at the 3-month follow-up, compared to bevacizumab (p = 0.003), aflibercept (p = 0.015), and ranibizumab (p < 0.001); Aflibercept exhibited a superior effect than ranibizumab (p = 0.001). At 1-year follow-up, aflibercept resulted in a more significant reduction of macular thickness compared to ranibizumab (p = 0.016) while no significant differences were observed among the other drugs. CONCLUSIONS: Our practical experience showed the effectiveness of the new setting in the treatment of wAMD. This comparative study at 1 year suggested a predominant brolucizumab efficacy on functional outcomes. In addition, brolucizumab and aflibercept appeared to have similar efficacy in fluid control.

Optical coherence tomography biomarkers indicating visual enhancement in diabetic macular edema resolved through anti-VEGF therapy: OCT biomarkers in resolved DME.

PURPOSE: to investigate the structural features and extended visual results in eyes affected by diabetic retinopathy (DR) and diabetic macular edema (DME) that have been successfully treated with anti-vascular endothelial growth factor (VEGF) therapy. METHODS: Individuals (39 eyes of 39 patients) who had undergone long-term follow-up and demonstrated evidence of resolved DME after at least 2 years of follow-up following the initiation of anti-VEGF therapy were included. During the ""study visit"", structural OCT scans were examined to assess qualitative features indicative of neuroretina or retinal pigment epithelium distress. Additionally, a quantitative assessment of the inner and outer retinal thicknesses was conducted for topographical analysis. RESULTS: The most robust qualitative association observed with BCVA at the "study visit" was linked to the presence of DRIL (p = 0.043) and the appearance of the ELM. (p = 0.045). Regarding quantitative parameters, a strong correlation was noted between the visual acuity during the "study visit" and the foveal and parafoveal thicknesses of both the inner and outer retina (p < 0.001). CONCLUSIONS: Changes in the status of ELM, the presence of DRIL, and the thicknesses of the foveal and parafoveal regions can act as OCT biomarkers, signifying prolonged visual improvements in eyes that have experienced resolved DME after undergoing anti-VEGF therapy.

Microperimetric evaluation and predictive factors of visual recovery after successful inverted internal limiting membrane-flap technique for macular hole in high myopic eyes.

Introduction: Inverted Internal Limiting Membrane (ILM)-flap technique demonstrated its effectiveness, in terms of anatomical closure rate and visual acuity recovery for high myopic macular holes. We evaluated macular function after a successful inverted ILM-flap for macular holes in high myopic eyes (hMMH) using microperimetry to predict visual prognosis. Methods: A retrospective study on 23 eyes of 23 patients after surgical closure of hMMH, was performed. All patients underwent inverted ILM-flap and gas tamponade. Cataract surgery was performed in phakic eyes. Study outcomes including best-corrected visual acuity (BCVA), retinal sensitivity (RS) at central 12°, central retinal sensitivity (CRS) at central 4° and mean deviation (MD), and fixation behavior as bivariate contour ellipse area (BCEA, degrees2) measured by microperimetry, were evaluated over 6 months. A mixed-effects model was used to evaluate and compare the repeated measurements of outcomes between phakic and pseudophakic eyes. A regression model was performed to assess the relationship between BCVA at 6 months and independent variables. Results: Overall mean BCVA improved from 0.98 ± 0.21 logMAR at baseline to 0.47 ± 0.31 logMAR at the last follow-up (p < 0.001). Over 6 months, overall sensitivity measurements improved (RS, p = 0.001; CRS, p < 0.0001; MD, p = 0.03), and the BCEA decreased in dimension, although not significantly (p ≥ 0.05). The mixed model revealed a significantly better effect of inverted ILM-flap combined with cataract surgery on BCVA and CRS in phakic eyes than inverted ILM-flap alone in pseudophakic ones. The regression model revealed a relationship of 6-month BCVA with pre-operative BCVA (ß = 0.60, p = 0.02) and RS (ß = -0.03, p = 0.01). Conclusion: The inverted ILM-flap technique significantly improved visual acuity and retinal sensitivity after the hMMH closure, particularly when combined with cataract extraction. Pre-operative visual acuity and retinal sensitivity at central 12° may predict post-surgical visual acuity.

SEVERE VISUAL LOSS DURING ANTI-VEGF INTRAVITREAL INJECTIONS IN NEOVASCULAR AGE-RELATED MACULAR DEGENERATION: TIMING, PROGNOSIS, AND OPTICAL COHERENCE TOMOGRAPHY FINDINGS.

PURPOSE: Intravitreal injection (IVI) of anti-vascular endothelial growth factor (VEGF) is the standard of care for neovascular age-related macular degeneration (nAMD). However, a small subgroup of patients still experience severe visual impairment, which may be related to the number of IVI administered. METHODS: This retrospective observational study analyzed data from patients with sudden severe visual decline (≥15 Early Treatment Diabetic Retinopathy Study [ETDRS] letters loss between two consecutive IVIs) during anti-VEGF treatment for nAMD. Best-corrected visual acuity examination, optical coherence tomography (OCT), and OCT angiography (OCTA) were performed before every IVI and central macular thickness (CMT) and drug injected were collected. RESULTS: 1,019 eyes received anti-VEGF IVI for nAMD from December 2017 to March 2021. Severe VA loss occurred in 15.1% after a median of 6 (range 1-38) IVI. Ranibizumab was injected in 52.8% and aflibercept in 31.9% of cases. Functional recovery after 3 months was significant, without further improvement at 6 months. Visual prognosis relative to the percentage of CMT change showed better visual outcome in eyes with no substantial change in CMT compared with an increase of >20% or a decrease of >5%. CONCLUSION: In this first real-life study exploring severe VA loss during anti-VEGF treatment in patients with nAMD, it was found that it was not unusual for a ≥15 ETDRS letters loss to occur between two consecutive IVIs, often within 9 months of diagnosis and 2 months after the last IVI. Close follow-up and a proactive regimen should be preferred, at least in the first year.

Short-Term Morphofunctional Changes in Previously Treated Neovascular AMD Eyes Switched to Brolucizumab.

The purpose of the study is to explore the morphofunctional fluctuations in eyes treated for neovascular AMD (nAMD) when treatment is switched from aflibercept or ranibizumab to brolucizumab. A total of 31 eyes of 31 patients with nAMD with type 1 macular neovascularization (MNV) were included. All patients were imaged using spectral domain optical coherence tomography (SD-OCT). The OCT acquisition was performed at the following visits: (i) "T1 visit" corresponding to the last follow-up examination in which an intravitreal injection of aflibercept or ranibizumab was performed before switching to brolucizumab because of the lack of improvement and (ii) "T2 visit" corresponding to the examination performed 1 month after T1, the latter visit corresponding to the day when a switch to brolucizumab injection was performed, (iii) and 1 month after the latter injection "(T3)". The main outcome measures were: (1) central macular thickness (CMT), (2) choroidal vascularity index (CVI), (3) subfoveal choroidal thickness (CT), and best-corrected visual acuity (BCVA). Functional outcome showed significant differences at each time. Mean ± SD BCVA was 0.43 ± 0.12 LogMAR at T1 and 0.56 ± 0.16 LogMAR at T2 (p = 0.038). A significant improvement in BCVA was displayed at T3 (0.34 ± 0.21 LogMAR) as compared with T2 (p = 0.019). CMT analysis showed fluctuations three times. In detail, T2 displayed a thicker CMT in comparison with T1, although not statistically significant (p = 0.12). Contrariwise, T3 showed a thinner CMT in comparison with T2 (p = 0.002). Analyzing CVI among the three different times, the luminal choroidal area (LCA) and total choroidal area (TCA) showed significantly different values before and after switching to brolucizumab. T2 showed a significant reduction in both vessel lumen and total area compared with T1 (p = 0.032 and p = 0.046, respectively). Moreover, T3 showed a greater value of both LCA and TCA in comparison with T2 (p = 0.008 and p = 0.01, respectively). CT did not show significant differences at each time (p > 0.05). Our results reported early experiences on morphofunctional fluctuations in patients with nAMD who switched to brolucizumab. The anatomical impact of brolucizumab administration appears to result in choroidal vascular enlargement, accompanied by the resolution of subretinal fluid (SRF) and intraretinal fluid (IRF).

Topographical Analysis of the Choriocapillaris Reperfusion After Loading Anti-VEGF Therapy in Neovascular AMD.

Purpose: The purpose of this study was to evaluate choriocapillaris vascular density changes around macular neovascularization (MNV) before and after anti-vascular endothelium growth factor (VEGF) injections by optical coherence tomography angiography (OCTA). Methods: Treatment-naïve eyes with a diagnosis of exudative AMD and type 1 MNV were included. En face optical coherence tomography angiograms were analyzed for percentage of choriocapillaris (CC) flow deficit percentage (FD%), the FD average area (FDa), and the FD number (FDn) in 5 progressive 200-µm-wide concentric rings (R1, R2, R3, R4, and R5) surrounding the dark halo around the MNV. The OCTA acquisition was performed at the following visits: (i) before the loading phase of intravitreal injection of aflibercept or ranibizumab (T1), and (ii) 1 month after the last intravitreal injection of loading phase comprising 3 monthly injections (T2). Results: A total of 30 eyes of 30 Caucasian patients with treatment naïve neurovascular AMD (nAMD) were included in the study. All rings showed a progressive FD% reduction at T2 in comparison to T1 values indicating gradual CC reperfusion of the peripheral rings. Furthermore, we found a progressive contraction of the FD average area in all the rings considered (P < 0.05). On the other hand, at T2, a significant increase in the FD number of the 5 rings was displayed, as compared to T1 (P < 0.05). Conclusions: Our analysis showed topographical CC reperfusion after loading anti-VEGF therapy. CC flow deficits were greater around the associated dark halo before treatment, followed by a progressive recovery of CC flow after intravitreal therapy. Translational Relevance: OCTA may be used to assess the development and progression of MNV but also in assessing response to intravitreal injections of anti-VEGF.

Implementation of Lean healthcare methodology in designing an Intravitreal Injection Center: first Italian experience.

PURPOSE: The principles of the Lean methodology, introduced by Toyota to improve productivity, are relevant to other settings, including healthcare. We aimed to use Lean methodology to design a new setting in our ophthalmology clinic to improve the management of patients receiving an intravitreal injection for ocular diseases. METHODS: The location of services, days of operation, scheduling and processing of patients, utilization of staff, data recording methods, and examination and surgical procedures were analyzed, and a new Intravitreal Injection Center was developed according to Lean principles. RESULTS: The new setting, which is confined to a single floor, in contrast to the previous system, which necessitated that patients visit various locations spread over three floors of the hospital, demonstrated benefits for patients and improved the flow and management of patients through the system with a need for fewer team members. The intravitreal injection service improved with regard to both the quality and speed of the overall procedure and the efficient use of staff. CONCLUSION: Our aim to achieve a fast and one-way route to move patients through intravitreal injection administration was achieved, limiting any waste of time and space and improving the capacity management of the center. The system is of relevance to other ophthalmology clinic settings and facilitates the collection of valuable epidemiological and clinical information on the response of patients to different drugs and treatment regimens.