International Classification System for Ocular Complications of Anti-Vascular Endothelial Growth Factor Agents in Clinical Trials.

OBJECTIVE: Complications associated with intravitreal anti-vascular endothelial growth factor (VEGF) therapies are inconsistently reported in the literature, thus limiting an accurate evaluation and comparison of safety between studies. This study aimed to develop a standardized classification system for anti-VEGF ocular complications using the Delphi consensus process. DESIGN: Systematic review and Delphi consensus process. PARTICIPANTS: 25 international retinal specialists participated in the Delphi consensus survey. METHODS: A systematic literature search was conducted to identify complications of intravitreal anti-VEGF agent administration based on randomized controlled trials (RCTs) of anti-VEGF therapy. A comprehensive list of complications was derived from these studies, and this list was subjected to iterative Delphi consensus surveys involving international retinal specialists that voted on inclusion, exclusion, rephrasing, and addition of complications. As well, surveys determined specifiers for the selected complications. This iterative process helped refine the final classification system. MAIN OUTCOME MEASURES: The proportion of retinal specialists who choose to include or exclude complications associated with anti-VEGF administration. RESULTS: After screening 18,229 articles, 130 complications were initially categorized from 145 included RCTs. Participant consensus via the Delphi method resulted in the inclusion of 91 (70%) complications after three rounds. After incorporating further modifications made based on participant suggestions, such as rewording certain phrases and combining similar terms, 24 redundant complications were removed, leaving a total of 67 (52%) complications in the final list. A total of 14 (11%) complications met exclusion thresholds and were eliminated by participants across both rounds. All other remaining complications not meeting inclusion or exclusion thresholds were also excluded from the final classification system after the Delphi process terminated. In addition, 47 out of 75 (63%) proposed complication specifiers were included based on participant agreement. CONCLUSION: Using the Delphi consensus process, a comprehensive, standardized classification system consisting of 67 ocular complications and 47 unique specifiers was established for intravitreal anti-VEGF agents in clinical trials. The adoption of this system in future trials could improve consistency and quality of adverse event reporting, potentially facilitating more accurate risk-benefit analyses.

Long-term predictors of anti-VEGF treatment response in patients with neovascularization secondary to CSCR: a longitudinal study.

PURPOSE: To identify the baseline predictors of anti-VEGF treatment response at 3 years in patients affected by choroidal neovascularization (CNV) secondary to central serous chorioretinopathy (CSCR). METHODS: In this retrospective longitudinal study, medical records of patients diagnosed with CNV secondary to CSCR and treated using anti-VEGF injections between April 2015 and May 2020 were reviewed. The potential qualitative and quantitative predictors of treatment response were identified or measured based on the multimodal imaging examination available for each patient at the baseline, including structural OCT, fluorescein angiography (FA), indocyanine green angiography (ICGA), and OCT-angiography (OCT-A). Univariate and multivariate analyses were performed. RESULTS: Twenty-nine eyes from 29 patients affected by CNV complicating CSCR were included in the study. At the end of the 3-year follow-up, the mean BCVA was 20/50 Snellen equivalent (0.38 ± 0.36 LogMAR), and no significant difference with baseline BCVA (0.37 ± 0.29 LogMAR) was found (p = 0.9). Twenty out of 29 eyes (69%) had active lesions at the end of the follow-up. At multivariate analysis, none of the included features was independently associated with the 3-year BCVA outcome. Pigment epithelium detachment (PED) height (ß = 0.017, p = 0.028) and outer limiting membrane (OLM) preservation at the fovea (ß = -5.637, p = 0.026) were independently associated with the CNV activity at 3 years. CONCLUSION: PED height and OLM obliteration at the fovea might be considered baseline predictors of lesion activity at 3-year follow-up in patients with CNV secondary to CSCR treated with anti-VEGF therapy.

Deep learning for automatic prediction of early activation of treatment naïve non-exudative MNVs in AMD.

BACKGROUND: Around 30% of non-exudative macular neovascularizations(NE-MNVs) exudate within 2 years from diagnosis in patients with age-related macular degeneration(AMD).The aim of the study is to develop a deep learning classifier based on optical coherence tomography(OCT) and OCT angiography(OCTA) to identify NE-MNVs at risk of exudation. METHODS: AMD patients showing OCTA and fluorescein angiography (FA) documented NE-MNV with a 2-years minimum imaging follow-up were retrospectively selected. Patients showing OCT B-scan-documented MNV exudation within the first 2 years formed the EX-GROUP while the others formed QU-GROUP.ResNet-101, Inception-ResNet-v2 and DenseNet-201 were independently trained on OCTA and OCT B-scan images. Combinations of the 6 models were evaluated with major and soft voting techniques. RESULTS: Eighty-nine (89) eyes of 89 patients with a follow-up of 5.7 ± 1.5 years were recruited(35 EX GROUP and 54 QU GROUP). Inception-ResNet-v2 was the best performing among the 3 single convolutional neural networks(CNNs).The major voting model resulting from the association of the 3 different CNNs resulted in improvement of performance both for OCTA and OCT B-scan (both significantly higher than human graders' performance). Soft voting model resulting from the combination of OCTA and OCT B-scan based major voting models showed a testing accuracy of 94.4%. Peripheral arcades and large vessels on OCTA enface imaging were more prevalent in QU GROUP. CONCLUSIONS: Artificial intelligence shows high performances in identifications of NE-MNVs at risk for exudation within the first 2 years of follow up, allowing better customization of follow up timing and avoiding treatment delay. Better results are obtained with the combination of OCTA and OCT B-scan image analysis.

FROM DRUSEN TO TYPE 3 MACULAR NEOVASCULARIZATION.

PURPOSE: To investigate the imaging features preceding the occurrence of type 3 (T3) macular neovascularization (MNV) using tracked spectral-domain optical coherence tomography. METHOD: From a cohort of eyes with T3 MNV and ≥ 12 months of previously tracked spectral-domain optical coherence tomography, T3 lesions that developed above soft drusen were selected for optical coherence tomography analysis. Retinal imaging findings at the location where type T3 MNV occurred were analyzed at each follow-up until the onset of T3 MNV. The following optical coherence tomography parameters were assessed: drusen size (height and width), outer nuclear layer/Henle fiber layer thickness at the drusen apex, and the presence of intraretinal hyperreflective foci, retinal pigment epithelium disruption, incomplete retinal pigment epithelium and outer retina atrophy, and complete retinal pigment epithelium and outer retina atrophy. RESULTS: From a cohort of 31 eyes with T3 MNV, T3 lesions developed above soft drusen in 20 eyes (64.5%). Drusen showed progressive growth ( P < 0.001) associated with outer nuclear layer/Henle fiber ( P < 0.001) thinning before T3 MNV. The following optical coherence tomography features were identified preceding the occurrence of T3 MNV, typically at the apex of the drusenoid lesion: disruption of the external limiting membrane/ellipsoid zone and/or the retinal pigment epithelium, hyperreflective foci, and incomplete retinal pigment epithelium and outer retina atrophy/complete retinal pigment epithelium and outer retina atrophy. CONCLUSION: The results demonstrate specific anatomic alterations preceding the occurrence of T3 MNV that most commonly originates above soft drusen. Drusen growth, reduced outer nuclear layer/Henle fiber thickness, and retinal pigment epithelium atrophy at the drusen apex precede the development of T3 MNV. Identifying these optical coherence tomography features should warrant close monitoring for identification of T3 MNV, which can benefit from prompt intravitreal anti-vascular endothelial growth factor therapy.

NONEXUDATIVE INTRARETINAL FLUID IN INTERMEDIATE AGE-RELATED MACULAR DEGENERATION.

BACKGROUND: To describe the occurrence of nonexudative intraretinal fluid (IRF) in intermediate age-related macular degeneration. METHODS: A retrospective study was designed to include consecutive cases with intermediate age-related macular degeneration associated with IRF. A multimodal imaging approach was used to confirm diagnosis of IRF in intermediate age-related macular degeneration. Multimodal imaging included color fundus photograph, fundus autofluorescence, fluorescein angiography, indocyanine green angiography, optical coherence tomography, and optical coherence tomography angiography. RESULTS: Ten eyes of 10 patients (2 male and 8 female patients, ages 68-80 years) showing IRF in intermediate age-related macular degeneration were included in the study. The mean best-corrected visual acuity was 20/40 Snellen equivalent. Multimodal imaging including fluorescein angiography/indocyanine green angiography and optical coherence tomography demonstrated the absence of macular neovascularization in all cases; optical coherence tomography-angiography did not detect any abnormal flow signal associated with IRF. Seven of 10 patients developed IRF in correspondence of pigment epithelium detachment. Three of 10 patients presented IRF in correspondence of an area of nascent geographic atrophy. CONCLUSION: Nonexudative intraretinal fluid in intermediate age-related macular degeneration is a novel, distinctive feature that is characterized by the presence of IRF with no evidence of macular neovascular lesions. The authors described different phenotypes of IRF in intermediate age-related macular degeneration. The definite diagnosis of this condition requires further studies with thorough application of multimodal imaging.

PHENOTYPIC CHARACTERIZATION OF PREDICTORS FOR DEVELOPMENT AND PROGRESSION OF GEOGRAPHIC ATROPHY USING OPTICAL COHERENCE TOMOGRAPHY.

PURPOSE: To evaluate the impact of optical coherence tomography phenotypes preceding atrophy related to age-related macular degeneration on the progression of atrophic lesions. METHODS: In this observational retrospective cohort study, a total of 70 eyes of 60 consecutive patients with intermediate age-related macular degeneration with a minimum follow-up of 24 months were included. The atrophy was quantified using fundus autofluorescence, also considering the directionality of atrophy as centrifugal and centripetal progression rates. The main outcome measures were geographic atrophy (GA) progression rate (mm 2 /year) and square root transformation of GA (mm 2 /year). RESULTS: The best-fit model for GA (odds ratio: 1.81, P < 0.001) and square root transformation of GA (odds ratio: 1.36, P < 0.001) areas revealed that the main baseline predictor was the presence of a retinal pigment epithelium-basal lamina-Bruch membrane splitting. Large drusen at baseline appeared protective for the GA area lesion expansion over time (odds ratio: 0.52, P < 0.001) when considered with other confounders. CONCLUSION: A thin retinal pigment epithelium-basal lamina-Bruch membrane splitting without evidence of neovascularization on optical coherence tomography angiography likely represents an optical coherence tomography signature for late basal laminar deposits. Identifying this phenotype can help identify individuals with a higher risk of rapid progression and atrophy expansion.

Artificial intelligence in age-related macular degeneration: state of the art and recent updates.

Age related macular degeneration (AMD) represents a leading cause of vision loss and it is expected to affect 288 million people by 2040. During the last decade, machine learning technologies have shown great potential to revolutionize clinical management of AMD and support research for a better understanding of the disease. The aim of this review is to provide a panoramic description of all the applications of AI to AMD management and screening that have been analyzed in recent past literature. Deep learning (DL) can be effectively used to diagnose AMD, to predict short term risk of exudation and need for injections within the next 2 years. Moreover, DL technology has the potential to customize anti-VEGF treatment choice with a higher accuracy than expert human experts. In addition, accurate prediction of VA response to treatment can be provided to the patients with the use of ML models, which could considerably increase patients' compliance to treatment in favorable cases. Lastly, AI, especially in the form of DL, can effectively predict conversion to GA in 12 months and also suggest new biomarkers of conversion with an innovative reverse engineering approach.

Comparison of peripheral extension, acquisition time, and image chromaticity of Optos, Clarus, and EIDON systems.

PURPOSE: To evaluate differences in acquisition time, peripheral extension, and chromaticity between 3 different commercialized ultra-wide-field (UWF) fundus cameras. METHODS: Patients were prospectively enrolled from 07/2021 to 11/2021. Patients underwent fundus photography with the following scanning protocols: (1) single shot with Silverstone (Optos, California), two-shot montage with Clarus 500 (Carl Zeiss, Dublin, CA), and three-shot montage with iCare EIDON FA with UWF module (CenterVue Spa, a company of iCare Finland Oy; Vantaa, Finland). Acquisition time was calculated as the interval between the beginning and the end of the acquisition. Peripheral extension was quantified as the average ratio between the total retinal pixel area and the optic nerve head (ONH) pixel area. The average chromaticity of all pixels in the red-green-blue (RGB) space was calculated. RESULTS: Twenty-three eyes of 13 prospectively enrolled healthy controls were included in the study. Optos Silverstone had a higher total retina area/ONH area ratio (509.1 [480.9;559.3]) compared to Zeiss Clarus (442.0 [431.9;510.5], p = 0.02) and iCare EIDON (369.7 [345.3;387.8], p < 0.0001). Silverstone demonstrated the shortest acquisition time (median [interquartile range]: 32 [20;58.5] s) compared to Zeiss Clarus (42 [28.5;53.5] s, p = 0.6733) and iCare EIDON (72 [68.5;78] s, p = 0.0003). iCare EIDON demonstrated the lowest variability of acquisition time (9.5 s), compared to Zeiss Clarus (25 s) and Optos Silverstone (38.5 s). A statistically significant difference was found in the RGB distribution between each of the 3 devices (p < 0.001). iCare EIDON demonstrated an average barycenter position (RGB = [0.412, 0.314, 0.275]) that represented the best color balance of the image. Zeiss Clarus had a noticeable red shift at the expense of the blue and green channels (RGB = [0.515, 0.294, 0.191]). Optos Silverstone showed an absence of the blue channel (RGB = [0.621, 0.372, 0.007]) which results in a distortion of the color of the image. CONCLUSION: Optos Silverstone and Zeiss Clarus required less time than iCare EIDON to acquire a comparable size image and captured larger areas of the retina than iCare EIDON. iCare EIDON provided more color-balanced retinal images with greater richness of color content than the other two devices.

Individual vs. combined imaging modalities for diagnosing neovascular central serous chorioretinopathy.

PURPOSE: To assess the diagnostic accuracy of individual and combined imaging modalities compared with multimodal imaging for the detection of choroidal neovascularization (CNV) in central serous chorioretinopathy (CSC). METHODS: We analyzed patients with CSC with and without CNV who had indocyanine green angiography (ICGA), structural optical coherence tomography (OCT), and OCT angiography (OCTA) obtained on the same day. The presence of CNV was determined using multimodal imaging by a senior retina specialist (i.e., diagnostic reference). Individual and combined (i.e., ICGA + structural OCT) imaging modalities were then graded by two expert readers for the presence of CNV. Sensitivity, specificity, positive (PPV), and negative (NPV) predictive values were computed for individual and combined imaging modalities relative to the diagnostic reference. RESULTS: CNV was detected in 17 eyes in 17 out of 33 CSC patients according to the reference standard. Using ICGA, the identification of CNV had a sensitivity of 66.7%, specificity of 66.7%, PPV of 70.6%, and NPV of 62.5%. Structural OCT had the following diagnostic accuracy values: 83.3% of sensitivity, 53.3% of specificity, 68.1% of PPV, and 72.7% of NPV. Using OCTA, CNV was graded to be present with a sensitivity of 77.8%, specificity of 86.7%, PPV of 87.5%, and NPV of 76.5%. The combination of ICGA and structural OCT granted the identification of CNV with a sensitivity of 83.3%, specificity of 86.7%, PPV of 88.2%, and NPV of 81.3%. CONCLUSIONS: OCTA has an elevated diagnostic accuracy in identifying CSC-associated CNV, though a combination of ICGA and structural OCT has a comparable diagnostic efficiency.

CHOROIDAL VASCULARITY INDEX IN HYDROXYCHLOROQUINE TOXIC RETINOPATHY: A Quantitative Comparative Analysis Using Enhanced Depth Imaging In Spectral Domain Optical Coherence Tomography.

PURPOSE: To investigate choroidal involvement in eyes of patients treated with hydroxychloroquine (HCQ), by quantifying the choroidal vascularity index (CVI) and other choroidal biomarkers. METHODS: Vertical enhanced depth imaging spectral domain optical coherence tomography (SD-OCT) scans were performed in eyes with either advanced-stage or mild HCQ toxic retinopathy, as well as in healthy age-matched and sex-matched controls. Based on SD-OCT scans, the subfoveal and mean choroidal thickness (ChT) was measured. The CVI, total choroidal area (TCA), luminal choroidal area (LCA), and stromal choroidal area (SCA) were calculated based on a binarization image process. These variables were computed and compared between the three groups (i.e., advanced stage, mild toxicity, and healthy controls). RESULTS: Forty-eight eyes of 47 patients under HCQ (26 eyes presented with advanced stage HCQ toxicity and 22 eyes with mild toxicity) and 34 eyes of 31 healthy controls were included. Both CVI and ChT were significantly different between the three groups ( P < 0.001, P < 0.001). When comparing the advanced stage toxicity group to healthy controls, both the subfoveal and the mean ChT were diminished ( P < 0.001). The CVI, TCA, LCA, and SCA were significantly lower in the advanced stage of toxicity group when compared with controls ( P < 0.001, <0.00001, <0.0001, and P = 0.0094, respectively). CONCLUSION: Our study suggests that eyes with HCQ toxic retinopathy, especially at advanced stages, present with choroidal impairment, giving further pathophysiological insights into the unfolding of this retinal toxicity.

ARTIFICIAL INTELLIGENCE'S ROLE IN DIFFERENTIATING THE ORIGIN FOR SUBRETINAL BLEEDING IN PATHOLOGIC MYOPIA.

PURPOSE: To identify salient imaging features to support human-based differential diagnosis between subretinal hemorrhage (SH) due to choroidal neovascularization (CNV) onset and SH without CNV (simple bleeding [SB]) in pathologic myopia eyes using a machine learning (ML)-based step-wise approach. METHODS: Four different methods for feature extraction were applied: GradCAM visualization, reverse engineering, image processing, and human graders' measurements. GradCAM was performed on a deep learning model derived from Inception-ResNet-v2 trained with OCT B-scan images. Reverse engineering consisted of merging U-Net architecture with a deconvolutional network. Image processing consisted of the application of a local adaptive threshold. Available OCT B-scan images were divided in two groups: the first group was classified by graders before knowing the results of feature extraction and the second (different images) was classified after familiarization with the results of feature extraction. RESULTS: Forty-seven and 37 eyes were included in the CNV group and the simple bleeding group, respectively. Choroidal neovascularization eyes showed higher baseline central macular thickness ( P = 0.036). Image processing evidenced in CNV eyes an inhomogeneity of the subretinal material and an interruption of the Bruch membrane at the margins of the SH area. Graders' classification performance improved from an accuracy of 76.9% without guidance to 83.3% with the guidance of the three methods ( P  = 0.02). Deep learning accuracy in the task was 86.0%. CONCLUSION: Artificial intelligence helps identifying imaging biomarkers suggestive of CNV in the context of SH in myopia, improving human ability to perform differential diagnosis on unprocessed baseline OCT B-scan images. Deep learning can accurately distinguish between the two causes of SH.

Real-Life Experience and Predictors of Visual Outcomes with Intravitreal Brolucizumab Switch for Treatment of Neovascular Age-Related Macular Degeneration.

INTRODUCTION: To analyze visual and anatomical outcomes after switch to intravitreal brolucizumab therapy in eyes affected by neovascular age-related macular degeneration (nAMD) previously treated with other intravitreal anti-vascular endothelial growth factor (anti-VEGF) agents. METHODS: Retrospective study of eyes with nAMD that underwent intravitreal brolucizumab at San Raffaele Hospital (Milan, Italy) or San Rocco Clinical Institute (Ome, Italy) between January 2021 and July 2022. All study eyes had persistent residual retinal fluid after receiving at least 3 intravitreal injections of other anti-VEGF agents prior to switch to brolucizumab. RESULTS: Among 66 eyes from 60 patients (35 males; mean age 76.5 ± 7.4 years) with nAMD, 43 (65.2%) eyes received a complete loading dose of 3 brolucizumab injections, while 15 (22.7%) and 8 (12.1%) eyes were treated with 2 or 1 brolucizumab injections, respectively. The average number of brolucizumab injections was 2.5 during 4.0 ± 2.0 months (mean interval between two injections of 51.2 days). Lower letter gains (<5 letter improvement from baseline) were found in eyes that did not complete a loading dose, after a greater number of previous anti-VEGF injections, after a longer duration of disease, and in eyes with a greater rate of macular atrophy at baseline. No serious ocular or systemic adverse events were found after switch to brolucizumab. CONCLUSION: nAMD eyes with persistent residual retinal fluid despite frequent anti-VEGF treatment can still gain functional and anatomical improvements after switch to brolucizumab therapy. Despite a relevant heterogeneity in patients' response to brolucizumab, we identified potential biomarkers for functional and anatomical improvement.

Pushing Retinal Imaging Forward: Innovations and Their Clinical Meaning - The 2022 Ophthalmologica Lecture.

Retinal imaging has greatly expanded our understanding of various pathological conditions. This article presents a summary of the key points covered during the 2022 Ophthalmologica Lecture held at the Euretina Congress in Hamburg. The first part of the article focuses on the use of optical coherence tomography angiography to examine and comprehend the choroid in age-related macular degeneration (AMD). Subsequently, we delve into the discussion of the "postreceptor neuronal loss" theory in AMD, which was studied using en face structural optical coherence tomography (OCT). Following that, we explore pertinent findings obtained through cross-sectional OCT in retinal and optic nerve diseases, such as AMD, diabetic macular edema, pathologic myopia, central serous chorioretinopathy, and Leber's hereditary optic neuropathy.

Neovascular age-related macular degeneration: advancement in retinal imaging builds a bridge between histopathology and clinical findings.

PURPOSE: To provide a review of the salient histological and imaging features in neovascular age-related macular degeneration (AMD) that will be integrated in order to have a better comprehension of the pathogenesis and clinical aspects of this disease. METHODS: A literature review of histology and imaging features in neovascular AMD was conducted. RESULTS: Histology has granted a detailed characterization of neovascular AMD ex vivo. In details, histological features in these eyes have offered important insights into the pathogenesis of neovascular AMD. In addition, histology donated a detailed characterization of the different types of macular neovascularization (MNV) that may complicate AMD. The introduction of optical coherence tomography angiography (OCTA) has enormously amplified our knowledge of neovascular AMD through in vivo assessment of the anatomical and pathological characteristics of this disease. New insights elucidating the morphological features of the choriocapillaris confirmed that this vascular structure plays a crucial role in the pathogenesis of neovascular AMD. OCTA also offered a detailed visualization of MNV complicating neovascular AMD. CONCLUSIONS: New imaging technologies offer a remarkable chance to build a bridge between histology and clinical findings in neovascular AMD.

Choroidal vascularity index in eyes with central macular atrophy secondary to age-related macular degeneration and Stargardt disease.

PURPOSE: To compare macular atrophy (MA) secondary to age-related macular degeneration (AMD) and Stargardt disease (STGD) using the choroidal vascularity index (CVI). METHODS: In this multicentric retrospective study, two distinct cohorts were collected: patients with MA secondary to AMD and MA secondary to STGD. All patients were investigated using a multimodal imaging approach, including CVI in the subfoveal 1000 µm area. Of note, the CVI is not influenced by aging, which allows comparisons between different cohorts. RESULTS: Seventy eyes were included: 35 eyes of 35 patients (mean age 78 ± 7 years) in the AMD group and 35 eyes of 35 patients (mean age 41 ± 16 years, p < 0.001) in the STGD group. Choroidal thickness was significantly lower in the AMD group in comparison to the STGD group (151 ± 80 µm vs 353 ± 105 µm, p < 0.001). The total choroidal area (TCA) was significantly greater in the STGD group in comparison to the AMD group (1.734 ± 0.958 mm2 vs 0.538 ± 0.391 mm2, respectively, p < 0.001). Interestingly, the CVI was significantly lower in AMD patients in comparison to STGD patients (27.322 ± 15.320% vs 49.880 ± 7.217%, respectively, p < 0.001), and this difference was confirmed in the subgroup of patients over 50 years old. CONCLUSION: Our results corroborate the hypothesis that large choroidal vessels were impaired to a greater extent in AMD than in STGD. CVI may help in differentiating AMD from STGD in the presence of MA, better understanding of the pathogenesis, and monitoring of therapeutic response.

SUBRETINAL TRANSIENT HYPOREFLECTIVITY IN AGE-RELATED MACULAR DEGENERATION: A Spectral Domain Optical Coherence Tomography Study.

PURPOSE: To describe and assess the prognostic significance of subretinal transient hyporeflectivity (STHR) on a novel spectral domain optical coherence tomography (SD-OCT) in age-related macular degeneration. METHODS: Consecutive patients with age-related macular degeneration (AMD) presenting STHR, defined as a small, well-defined, round subretinal, hyporeflective lesion, on SD-OCT and without exudative signs were included. Clinical examination and SD-OCT (SPECTRALIS, Heidelberg Engineering, Heidelberg, Germany) were analyzed at inclusion, 1 month before inclusion, and until the onset of exudative signs during the 12-month follow-up. RESULTS: Thirty-five STHR in 21 eyes of 20 patients were included. Among the 21 eyes, 2 eyes had early AMD, 1 eye had nonexudative asymptomatic macular neovascularization, and 18 eyes presented late AMD: 17 eyes neovascular AMD and 1 eye geographic atrophy. During the 2-month follow-up, 97.1% (34/35) of STHR disappeared. During the 12-month follow-up, 57.1% of eyes (12/21) developed exudative signs on 1 eye with early AMD and 11 eyes with neovascular AMD. CONCLUSION: Subretinal transient hyporeflectivity is a novel SD-OCT sign in patients with AMD. The eyes with isolated STHR should be closely monitored on a monthly basis to detect further exudation.

A COMMON FINDING IN FOVEAL-SPARING EXTENSIVE MACULAR ATROPHY WITH PSEUDODRUSEN IMPLICATES BASAL LAMINAR DEPOSITS.

PURPOSE: To characterize structural and clinical alterations preceding the diffuse macular atrophy in extensive macular atrophy with pseudodrusen (EMAP) and their evolution toward atrophic changes. METHODS: A retrospective chart review was performed of patients with early-onset reticular pseudodrusen (i.e., pre-EMAP) younger than 55 years and EMAP with foveal sparing. Patients were included if they had complete medical records and multimodal imaging. RESULTS: A total of 12 patients were reviewed, of whom 4 of 12 patients (7 eyes) presented a pre-EMAP stage, characterized by the presence of pseudodrusen-like deposits without atrophic changes, while the remaining 8 of 12 patients (10 eyes) exhibited EMAP with foveal sparing (60.1 ± 6.4 years). Subretinal deposits of various stages tended to fade, leaving subretinal pigment epithelium accumulation of hyperreflective material with a physical separation between the retinal pigment epithelium-basal lamina and the Bruch membrane, along with the persistence of hyperreflective material after retinal pigment epithelium loss. These findings preceded atrophy development in a pre-EMAP stage and the EMAP stage with foveal sparing. CONCLUSION: Our findings presented distinct multimodal imaging features in eyes with reticular pseudodrusen depicting a peculiar phenotype of rapidly progressing atrophy in midlife. The disease spectrum may include other forms of geographic atrophy allied by thickened basal laminar deposits.

INNER AND OUTER CHOROIDAL CHANGES IN THE FELLOW EYE OF PATIENTS WITH UNILATERAL CENTRAL SEROUS CHORIORETINOPATHY.

PURPOSE: To quantitatively evaluate the inner and outer choroidal changes in the fellow eyes of patients with unilateral central serous chorioretinopathy (CSC). METHODS: We analyzed data from patients with a diagnosis of unilateral CSC who had structural optical coherence tomography (OCT) and swept-source OCT angiography obtained. An additional group of age-matched healthy patients was included for comparison. The main outcome measures were: (1) choriocapillaris flow deficits' quantitative metrics; (2) choroidal luminal (LCA) and stromal (SCA) areas; and (3) choroidal vascularity index. RESULTS: Fellow unaffected eyes from 60 patients with unilateral CSC and 30 healthy subjects were included in the analysis. Mean ± SD age was 47.5 ± 9.9 years in the unilateral CSC group and 50.7 ± 10.8 years in the control group (P = 0.410). In the structural OCT assessment, both the LCA and SCA were increased in the unilateral CSC group (0.33 ± 0.11 and 0.29 ± 0.10 mm2) compared with healthy controls (0.28 ± 0.08 and 0.27 ± 0.05 mm2), although only differences in LCA reached a statistical significance (P = 0.041 and P = 0.286 for LCA and SCA, respectively). The choroidal vascularity index was higher in CSC patients (53.7 ± 3.6 and 50.9 ± 5.5%, P = 0.045). In the OCT angiography evaluation, the choriocapillaris flow deficits' percentage and number were increased in those patients affected by unilateral CSC. In multiple regressions, the strongest association with choriocapillaris percentage of flow deficits was with the presence of pachychoroid pigment epitheliopathy signs in the study eye (P < 0.0001). CONCLUSION: Our results corroborate the hypothesis that inner and outer choroidal changes affect both eyes of patients with unilateral disease.

CHOROIDAL VASCULARITY INDEX IS ASSOCIATED WITH GEOGRAPHIC ATROPHY PROGRESSION.

PURPOSE: To investigate the correlation between choroidal vascularity index and the enlargement of geographic atrophy (GA) lesion secondary to age-related macular degeneration during the 2-year follow-up. METHODS: In this longitudinal observational study, 26 eyes (26 patients, mean age 75.7 ± 8.8 years) affected by GA were included. Choroidal vascularity index was calculated in the subfoveal 3000-µm area. The main outcome measure included correlation analysis between baseline choroidal vascularity index and the rate of GA enlargement. RESULTS: During the 2-year follow-up, the mean GA area increased from 6.99 ± 5.28 mm2 to 10.69 ± 6.61 mm2(P < 0.001), accounting for a growth rate of 0.35 ± 0.20 and 0.31 ± 0.17 mm/year after the square root transformation in the first and second year of follow-up, respectively. Stromal choroidal area significantly decreased during the 2-year follow-up (P = 0.002). Interestingly, there was a significant correlation between the baseline choroidal vascularity index and the rate of GA enlargement (r=-0.432, P = 0.027) and between stromal choroidal area and the rate of GA enlargement (r = 0.422, P = 0.032). No other significant relationship was disclosed among choroidal parameters with the rate of GA enlargement. CONCLUSION: Choroidal vascularity index impairment is strictly related to the rate of GA enlargement during the 1-year and 2-year follow-up in patients affected by GA. For this reason, choroidal vascularity index could be considered a predictor of GA progression in the clinical setting, and it could be considered as a new potential biomarker in the efficacy evaluation of new GA interventions.

FLUID-BASED VISUAL PROGNOSTICATION IN TYPE 3 MACULAR NEOVASCULARIZATION-FLIP-3 STUDY.

PURPOSE: To analyze the effect of fluid on visual acuity in cases of Type 3 macular neovascularization. METHODS: This multicentric, retrospective cohort study included eyes with treatment-naïve Type 3 macular neovascularization. Analysis of fluid in different compartments was performed. Group A included eyes with isolated intraretinal fluid, whereas Group B included eyes with intraretinal fluid in conjunction with subretinal fluid and/or sub retinal pigment epithelial fluid. RESULTS: Eyes in Group A (31, 55.3%) had better best-corrected visual acuity of 20/50 snellen equivalent (0.42 ± 0.31 logarithm of the minimum angle of resolution) at baseline and 20/50 snellen equivalent (0.40 ± 0.28 logarithm of the minimum angle of resolution) at complete resolution compared with Group B with visual acuity of 20/80 snellen equivalent (0.64 ± 0.35 logarithm of the minimum angle of resolution) (P = 0.0181) at baseline and 20/100 snellen equivalent (0.70 ± 0.40 logarithm of the minimum angle of resolution) (P = 0.0021) at complete resolution. Subfoveal atrophy was more in Group B (82.6% 19/23) at complete resolution in comparison to Group A (16/31, 51.6%). Eyes in Group B needed more anti-vascular endothelial growth factor injections (10.3 ± 9.0) for complete resolution compared with Group A (5.7 ± 4.8). CONCLUSION: Intraretinal fluid may be associated with good visual acuity in Type 3 macular neovascularization in contrast to other forms of neovascular age related macular degeneration. Furthermore, intraretinal fluid in isolation may need fewer injections and could probably be associated with less subfoveal atrophy.