LONG-TERM VISUAL OUTCOMES AND OPTICAL COHERENCE TOMOGRAPHY BIOMARKERS IN EYES WITH MACULAR EDEMA SECONDARY TO RETINAL VEIN OCCLUSION FOLLOWING ANTI-VASCULAR ENDOTHELIAL GROWTH FACTOR THERAPY.

PURPOSE: To evaluate the structural characteristics and long-term visual outcomes in eyes impacted by macular edema as a consequence of retinal vein occlusion that has undergone effective treatment with anti-vascular endothelial growth factor therapy. METHODS: Inclusion criteria comprised 42 eyes of 41 patients, subjected to long-term follow-up, displaying resolved macular edema after a minimum of 5 years since the commencement of anti-vascular endothelial growth factor therapy. During the final visit, two experienced observers evaluated several qualitative parameters using spectral-domain optical coherence tomography, such as the integrity of the external limiting membrane, the state of the ellipsoid zone and retinal pigment epithelium, and the presence of disorganization of the retinal inner layers. In addition, a quantitative evaluation of the inner and outer retinal thicknesses was conducted for the purpose of topographical analysis. RESULTS: The most prominent qualitative correlation identified with best-corrected visual acuity during the final visit was connected to the presence of disorganization of the retinal inner layers ( P = 0.004) and the integrity of the external limiting membrane ( P = 0.015). In relation to quantitative aspects, a noteworthy correlation was noted between the visual acuity during the last visit and the parafoveal thickness in both the inner ( P = 0.003) and outer retina ( P = 0.018). CONCLUSION: In eyes where macular edema resulting from retinal vein occlusion has been successfully resolved with anti-vascular endothelial growth factor therapy, changes in the status of the external limiting membrane and the presence of disorganization of the retinal inner layers serve as valuable optical coherence tomography biomarkers, indicating prolonged visual outcomes.

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.

Multimodal imaging in diabetic retinopathy and macular edema: An update about biomarkers.

Diabetic macular edema (DME), defined as retinal thickening near, or involving the fovea caused by fluid accumulation in the retina, can lead to vision impairment and blindness in patients with diabetes. Current knowledge of retina anatomy and function and DME pathophysiology has taken great advantage of the availability of several techniques for visualizing the retina. Combining these techniques in a multimodal imaging approach to DME is recommended to improve diagnosis and to guide treatment decisions. We review the recent literature about the following retinal imaging technologies: optical coherence tomography (OCT), OCT angiography (OCTA), wide-field and ultrawide-field techniques applied to fundus photography, fluorescein angiography, and OCTA. The emphasis will be on characteristic DME features identified by these imaging technologies and their potential or established role as diagnostic, prognostic, or predictive biomarkers. The role of artificial intelligence in the assessment and interpretation of retina images is also discussed.

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.

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.

Choroidal remodeling following different anti-VEGF therapies in neovascular AMD.

The purpose of this study was to investigate choroidal morphology remodeling in AMD-associated type 1 macular neovascularization using two different anti-VEGF drugs. We registered 73 treatment-naïve eyes with a diagnosis of exudative AMD and type 1 MNV. Patients received 3 monthly intravitreal aflibercept (n = 36, aflibercept group [AG]) or brolucizumab (n = 37, brolucizumab group [BG]). Baseline best-corrected visual acuity (BCVA) and anatomical (structural optical coherence tomography) parameters were collected at "T1 control", before the loading phase (LP) of intravitreal injection, and at "T2 control", 1 month after the last injection. The main outcomes measured were choroidal vascularity index (CVI), sub-foveal choroidal thickness (SFCT), and central macular thickness (CMT). Our results displayed significant SFCT reduction in both groups between T1 and T2 (p < 0.05), We did not find choroidal vascularity modifications (p > 0.05) after the loading aflibercept injections. Moreover, only the BG displayed a significant choroidal remodeling (stromal choroidal area [SCA], total choroidal area [TCA] and CVI) at T2 (p < 0.05). In particular, a relevant stromal and total choroidal volume reduction was noted, accompanied by an increase in CVI. To conclude, the latter modifications of the choroidal morphology were found significant between two groups (p < 0.05). Our analysis showed a significant impact of brolucizumab on choroidal morphology in eyes affected by type 1 nAMD. This effect was found relevant when compared with aflibercept.

Neurovascular retinal impairment in early-treated adults with phenylketonuria.

Purpose: To compare radial peripapillary capillary (RPC) vascular plexus parameters and peripapillary retinal nerve fiber layer (pRNFL) thickness between Early-Treated Adults with Phenylketonuria (ETPKU) and controls. Methods: This observational study was a monocentric, case control study including 36 eyes of 36 participants. Among these, 18 were early-treated PKU (ETPKU) and 18 were controls. A SD-OCTA (XR Avanti AngioVue OCTA; Optovue Inc., Fremont, CA) was employed to assess the OCT and OCTA parameters of all the participants. The main outcome measures were the RPC vessels density (VD) %, and the pRNFL thickness. Results: The average pRNFL thickness was significantly reduced in ETPKU (110.78 ± 12.48 µm) compared to controls (113.22 ± 13.95 µm), p = 0.046. The mean VD% of the small vessels of the RPC plexus was 52.31 ± 2.2 in ETPKU and 50.71 ± 3.2 in controls (p = 0.049), while the VD% of all the radial peripapillary capillary plexus (RPCP) was 58.5 ± 2.2 in ETPKU and 55.08 ± 3.4 in controls (p < 0.001). By contrast, there were no differences in age, sex, and IOP between the two groups. Conclusion: Through structural OCT and OCTA, we observed thinning of the nerve fibers accompanied by an increase in perfusion of the RPC plexus. Thus, our conclusions suggest that OCTA may serve as a noninvasive method to identify novel retinal biomarkers in ETPKU.