To investigate the correlation between morphological lesions and functional indicators in eyes with neovascular age-related macular degeneration (nAMD).
This was a prospective observational study of treatment-naïve nAMD eyes. Various morphological lesions and impaired retinal structures were manually measured at baseline and month-3 in three-dimensional optical coherence tomography (OCT) and optical coherence tomography angiography (OCTA) images, including the volumes (mm3) of macular neovascularization (MNV), avascular subretinal hyperreflective material (avascular SHRM), subretinal fluid (SRF), intraretinal fluid (IRF), serous pigment epithelial detachment (sPED) and the impaired area (mm2) of ellipsoid zone (EZ), external limiting membrane (ELM) and outer nuclear layer (ONL).
Sixty-three eyes were included. The volume of avascular SHRM showed persistent positive associations with the area of EZ damage, both at baseline, month-3, and change values (all P < 0.001). Poor BCVA (month-3) was associated with larger volumes of baseline IRF (β = 0.377, P < 0.001), avascular SHRM (β = 0.306, P = 0.032), and ELM impairment area (β = 0.301, P = 0.036) in multivariate model. EZ and ELM impairment were primarily associated with baseline avascular SHRM (β = 0.374, p = 0.003; β = 0.388, P < 0.001, respectively), while ONL impairment primarily associated with MNV (β = 0.475, P < 0.001).
The utilization of three-dimensional measurements elucidates the intrinsic connections among various lesions and functional outcomes. In particular, avascular SHRM plays an important role in prognosis of nAMD.

OBJECTIVE: To investigate the formation and absorption of avascular subretinal hyperreflective material (avSHRM) in neovascular age-related macular degeneration (nAMD) based on optical coherence tomography angiography (OCTA) characteristics.
METHODS: Prospective cohort study.
METHODS: This study included patients with treatment-naive nAMD who were followed up for 3 months. Subjects were classified into an avSHRM group and a non-avSHRM group based on the presence of avSHRM at baseline. Quantitative OCTA characteristics including explant area, perimeter, vessel area, density, length, junctions, endpoints, lacunarity, maximum vessel caliber, vessel dispersion, and fractal dimension were assessed, and 3-dimensional volume and optical density ratio (ODR) of avSHRM were measured. Comparison analyses, correlation coefficients, and regression models were applied to explore factors associated with avSHRM formation and absorption.
RESULTS: A total of 88 eyes from 88 patients (39 female) were enrolled. Compared to the non-avSHRM group, the avSHRM group exhibited a more intricate vasculature, characterized by higher values of macular neovascularization (MNV) perimeter, vessel area, total vessel length, total number of junctions, and total number of endpoints (all P < .05), as well as the maximum vessel caliber (P < .001). In the multivariate model, which was adjusted for age, sex, and types of medications, avSHRM absorption was correlated with baseline average vessel length, maximum vessel caliber, and avSHRM ODR (standardized β = 0.274, -0.367, and -0.334; P = .049, .010, and .018, respectively), with an adjusted R² of 0.453.
CONCLUSIONS: Quantitative OCTA measurements can be used for assessing the dynamics of avSHRM in nAMD. Patients with more complex vasculature are at higher risk for avSHRM formation. Average vessel length, maximum vessel diameter, and avSHRM ODR play a role in its absorption.

OBJECTIVE: This study evaluated the long-term outcomes of eyes with neovascular age-related macular degeneration (nAMD) treated with aflibercept according to a treat-and-extend (T&E) regimen for up to 5 years. Methods This retrospective study included 112 eyes of 111 patients with nAMD who received aflibercept according to the T&E regimen. The patients received 3 monthly injections of aflibercept followed by a T&E regimen for at least 12 months. Data, including best-corrected visual acuity (BCVA), treatment interval, presence of exudation, central retinal thickness, and central choroidal thickness were analyzed.
RESULTS: Of the 112 consecutive eyes, 66 completed the 5-year follow-up. After 5 years of treatment, BCVA (logMAR) was significantly better than baseline (0.29 ± 0.31 at baseline and 0.18 ± 0.23 at 5 years, P < 0.01). A mean of 7.0 ± 1.5 injections in the first year and 4.9 ± 2.2 injections per year thereafter were required. In eyes with subretinal hyperreflective material (SHRM) at baseline, BCVA at baseline and 5 years were significantly worse than in eyes without SHRM at baseline and 5 years. However, the eyes with SHRM required fewer injections and exhibited greater BCVA improvement.
CONCLUSIONS: This retrospective study demonstrated the effectiveness of the T&E regimen with aflibercept in managing nAMD over a 5-year period, maintaining significant improvements in BCVA.

OBJECTIVE: To examine retinal feature dynamics in eyes with neovascular age-related macular degeneration (nAMD) treated with anti-VEGF therapy and the relationship of these features with visual acuity.
METHODS: Post hoc analysis of the phase III, randomized, HAWK nAMD clinical trial.
METHODS: Participants randomized to the brolucizumab 6 mg or aflibercept 2 mg arms of the trial.
METHODS: Spectral-domain OCT scans collected at 4-week intervals were analyzed using an automated machine learning-enhanced segmentation and feature-extraction platform with manual verification. Quantitative volumetric measures of retinal and exudative features were exported at multiple timepoints over 48 weeks. Volatility of exudative features was calculated as the standard deviation of each feature value during the maintenance phase (week 12-48) of treatment. These features were examined for their associations with anatomic and functional outcomes.
METHODS: Longitudinal intraretinal fluid (IRF) and subretinal fluid (SRF) volume, subretinal hyperreflective material (SHRM) volume, ellipsoid zone (EZ) integrity (EZ-retinal pigment epithelium [RPE] volume/thickness), and correlation with best-corrected visual acuity (BCVA).
RESULTS: Intraretinal fluid, SRF, and SHRM demonstrated significant volumetric reduction from baseline with anti-VEGF therapy (P < 0.001 at each timepoint). Ellipsoid zone integrity measures demonstrated significant improvement from baseline (P < 0.001 at each timepoint). Both EZ integrity and SHRM measures correlated significantly with BCVA at all timepoints (EZ-RPE volume: 0.38 ≤ r ≤ 0.47; EZ-RPE central subfield thickness: 0.22 ≤ r ≤ 0.41; SHRM volume: -0.33 ≤ r ≤ -0.44). After treatment initiation, correlations of IRF and SRF volume with BCVA were weak or nonsignificant. Eyes with lower volatility of IRF, SRF, and SHRM volumes during the maintenance phase showed greater improvements in EZ integrity (all P < 0.01) and greater gains in BCVA (all P < 0.01) at week 48 compared with eyes with higher volatility in those exudative parameters.
CONCLUSIONS: Quantitative measures of SHRM volume and EZ integrity correlated more strongly with BCVA than retinal fluid volumes during treatment. High volatility of exudative parameters, including SRF, during the maintenance phase of treatment was associated with loss of EZ integrity and BCVA.
BACKGROUND: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Subretinal hyperreflective material (SHRM) is a common and remarkable optical coherence tomography (OCT) biomarker whose importance is emerging in several retinal and chorioretinal diseases, including age-related macular degeneration, central serous chorioretinopathy, polypoidal choroidal vasculopathy, pathologic myopia, posterior uveitis, vitelliform lesions and macular dystrophies, and rarer disorders. Multimodal imaging, also thanks to the introduction of OCT angiography, allowed a deeper characterisation of SHRM components and its morphological changes after treatment, suggesting its usefulness in clinical practice. We discuss and summarize the nature, multimodal imaging characteristics, and prognostic and predictive significance of SHRM in the different retinal and choroidal disorders in which it has been described.

To assess short-term efficacy of a single injection of brolucizumab in neovascular AMD.
This was a multicenter, retrospective chart review of 25 eyes of 25 patients who received a single injection of brolucizumab. Visual acuity (VA) and optical coherence tomography (OCT) features such as central subfield thickness (CSFT), subretinal fluid (SRF), intraretinal fluid, and pigment epithelial detachment (PED) were recorded at baseline, first month, and third month.
Of the 25 eyes, 14 eyes were treatment-naïve and 11 eyes had received previous injections. VA improved from 0.68 ± 0.59 log MAR at baseline to 0.31 ± 0.43 log MAR at the end of 3 months. SRF height in first and third month was significantly reduced from baseline (P < 0.001). Subretinal hyperreflective material height significantly reduced from baseline (P value 0.008 at first month and 0.01 at third month, respectively). CSFT was 464.16 ± 247.97 microns at baseline and showed a significant reduction in first month (P < 0.001) and third month (P < 0.001). There was a significant reduction of PED height from baseline at both follow-ups. None of the eyes showed a recurrence of fluid at the end of 3 months.
Our study demonstrated sustained improvement in VA and OCT parameters after a single injection of brolucizumab at 3 months. A longer follow-up may demonstrate even farther effects of a single injection.

BACKGROUND: This study aimed to report eleven cases of non-neovascular pachychoroid disease with hyperreflective material (HRM) that occurred in Japanese patients.
METHODS: A retrospective review of data from eleven patients who had non-neovascular retinal pigment epithelium (RPE) protrusion with HRM in the neurosensory retina between March 2017 and June 2022 was conducted. Clinical examination, color fundus photography, fluorescein angiography, spectral-domain optical coherence tomography (SD-OCT), and OCT angiography data were analyzed. Main outcome measures were patient characteristics, changes in SD-OCT findings, and symptom outcomes.
RESULTS: All cases had RPE protrusion and HRM with dilated choroidal veins, which were characteristic of pachychoroid disease. However, none of the cases had macular neovascularization (MNV). In 9 eyes (81.8%), HRM improved spontaneously without intervention and resulted in alterations in RPE, referred to as pachychoroid pigment epitheliopathy (PPE) or focal choroidal excavation (FCE). In these cases, symptoms such as metamorphopsia and distortion improved without treatment. In the remaining two cases (18.2%), HRM still persisted during the follow-up period.
CONCLUSIONS: There are some cases of non-neovascular pachychoroid disorder with HRM, which might be a new entity of pachychoroid spectrum disease or an early stage of PPE or FCE. These cases should not be misdiagnosed as MNV, and careful observation is necessary.

OBJECTIVE: To examine structural and clinical changes in previously treated type 1 macular neovascularization (MNV) in non-responder age-related macular degeneration (nAMD) eyes switched to brolucizumab. Subretinal hyper-reflective material (SHRM), intraretinal (IRF) and subretinal fluid (SRF) presence, fibrovascular-pigment epithelium detachment (PED) height and central macular thickness (CMT) variation were analyzed using optical coherence tomography (OCT).
METHODS: In this prospective study all patients underwent a complete ophthalmological evaluation including structural OCT at baseline (T0), one month (T1), three (T2), four (T3) and six months after switching to brolucizumab treatment (T4). Non-responder criterion was the persistence of IRF and SRF. Moreover, CMT and BCVA had shown worsening or no improvement before switching to brolucizumab. Clinical function and structural activity biomarkers were measured at each visit and changes were analyzed. P value <0.05 was considered statistically significant.
RESULTS: Twenty eyes of twenty patients were enrolled. All the structural variables examined during the follow-up showed significant reductions. Decreases in IRF, SRF and PED were already significant at T1 (p < 0.05). SHRM was significantly reduced at T2 (p < 0.05). Structural biomarkers were absent at T3. At T4, all biomarkers remained stable while SHRM was no longer detectable in 18 patients. Changes in visual acuity from baseline to T4 were not significant.
CONCLUSIONS: This short-term experience highlights that brolucizumab might be considered an effective treatment option in nAMD with type 1 MNV, as it can promote a reduction of structural activity biomarkers.

BACKGROUND: Subretinal hyperreflective material (SHRM) is a hyperrefiective material seen on optical coherence tomography (OCT) and located under the retina and above the retinal pigment epithelium. This study aims to examine the effect of SHRM on the functional prognosis of age-related macular degeneration (AMD) patients who switched from intravitreal ranibizumab to intravitreal aflibercept treatment.
METHODS: This is a retrospective, nonrandomized clinical study. AMD patients meeting the switching criteria underwent a complete ophthalmic examination, including spectral-domain OCT and fundus fluorescein angiography. The best-corrected visual acuity and OCT parameters were measured at the switch and 3, 6, 12, and 24 months after. SHRM(+/-), maximum SHRM thickness, and subjective and objective reflectivity stages of SHRM (grades 1-3) were evaluated.
RESULTS: SHRM was observed in 24/48 (50.0%) of eyes at the time of the switch. The differences in maximum SHRM thicknesses were not statistically significant. SHRM\'s mean subjective reflectivity stages at the switch and subsequent examinations were 2.37, 2.75, 2.75, 2.74, and 2.81; SHRM\'s objective reflectivity staging also confirmed them. Functional changes after the switch showed a significant VA loss in the SHRM(+) group and significant gain in the SHRM(-) group.
CONCLUSIONS: This study showed that the presence of SHRM and higher optical reflectivity at the switch from ranibizumab to aflibercept caused a poor prognosis after the switch. On the other hand, SHRM(-) patients achieved good functional results after the switch.

To evaluate the incidence of bacillary layer detachment among patients with neovascular age-related macular degeneration (nAMD) and their response to anti-VEGF therapy.
Post hoc analysis of the OSPREY clinical trial, a prospective, double-masked, phase II study comparing 6-mg brolucizumab with 2-mg aflibercept over 56 weeks.
Participants with treatment-naive nAMD at the initiation of the trial were included in the analysis (n = 81).
Spectral-domain OCT (SD-OCT) scans were obtained at 4-week intervals throughout the OSPREY study and were segmented automatically using a proprietary, machine learning-enabled higher-order feature-extraction platform.
The presence of bacillary detachment, and in these eyes the effect of anti-VEGF therapy on change from baseline in visual acuity (VA), central subfield thickness (CST), retinal fluid volumes, subretinal hyper-reflective material (SHRM) volume, subretinal pigment epithelium (sub-RPE) fluid volume, and ellipsoid zone (EZ) integrity at week 56.
Bacillary detachment was identified in 7.4% (6 of 81) eyes, which had higher fluid volumes, increased CST, EZ attenuation, and increased sub-RPE volume at baseline compared with eyes without bacillary detachment. Anti-VEGF treatment resulted in the resolution of bacillary detachment in 100% of the eyes. In eyes with bacillary detachment at baseline, the anti-VEGF treatment decreased CST, fluid burden, and SHRM volumes throughout the treatment course; however, there was no significant change from baseline in VA, sub-RPE volume, or EZ integrity throughout the 56-week course of anti-VEGF treatment.
Bacillary detachment is an OCT signature that is identifiable in a notable proportion of nAMD eyes. Anti-VEGF therapy resulted in 100% resolution of bacillary detachment and significant decreases in CST and SHRM volume; however, improvements in VA may have been limited by persistent EZ attenuation.