Mitochondrial retinopathies and optic neuropathies: The impact of retinal imaging on modern understanding of pathogenesis, diagnosis, and management.

Advancements in ocular imaging have significantly broadened our comprehension of mitochondrial retinopathies and optic neuropathies by examining the structural and pathological aspects of the retina and optic nerve in these conditions. This article aims to review the prominent imaging characteristics associated with mitochondrial retinopathies and optic neuropathies, aiming to deepen our insight into their pathogenesis and clinical features. Preceding this exploration, the article provides a detailed overview of the crucial genetic and clinical features, which is essential for the proper interpretation of in vivo imaging. More importantly, we will provide a critical analysis on how these imaging modalities could serve as biomarkers for characterization and monitoring, as well as in guiding treatment decisions. However, these imaging methods have limitations, which will be discussed along with potential strategies to mitigate them. Lastly, the article will emphasize the potential advantages and future integration of imaging techniques in evaluating patients with mitochondrial eye disorders, considering the prospects of emerging gene therapies.

Retinal OCT biomarkers associated with reading performance in patients with persistent vs. resolved diabetic macular edema.

BACKGROUND: Recent advancements in imaging technologies, particularly structural optical coherence tomography (OCT), have improved the understanding of diabetic macular edema (DME) pathophysiology and provided valuable biomarkers for disease progression and visual outcomes. This prospective study aimed to investigate the association between specific retinal biomarkers identified through OCT imaging and reading performance metrics in patients with previously treated persistent versus resolved DME and good visual acuity. METHODS: Forty-nine eyes from 35 patients with a history of DME were enrolled. Reading performance was assessed using the Radner reading charts, which include standardized sentences with geometrically progressing print sizes. Structural alterations in the inner and outer retina, as well as the retinal pigment epithelium (RPE), were graded based on OCT images. RESULTS: Reading performance, measured as maximum reading speed, was associated with specific retinal biomarkers. The disruption of the ellipsoid zone (EZ) in the parafoveal region and the presence of disorganization of the inner retinal layers (DRIL) in the parafovea were correlated with reduced reading speed. These associations were independent of the presence of intraretinal or subretinal fluid. CONCLUSIONS: Understanding the relationship between retinal biomarkers and reading performance could contribute to a comprehensive evaluation of visual function and quality of life in patients with DME, leading to better management strategies and treatment 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.

Short-Term Morpho-Functional Changes before and after Strabismus Surgery in Children Using Structural Optical Coherence Tomography: A Pilot Study.

PURPOSE: To evaluate the immediate alterations in the thickness of the macular ganglion cell-inner plexiform layer (mGCIPL), peripapillary retinal nerve fiber layer (RNFL), inner retinal layer (IRL), and outer retinal layer (ORL) using spectral domain optical coherence tomography (SD-OCT) subsequent to strabismus surgery in pediatric patients diagnosed with horizontal esotropia. METHODS: Twenty-eight eyes from twenty-one child patients who had undergone uncomplicated horizontal rectus muscle surgery due to strabismus were included. Measurements of RNFL, mGCL-IPL, IRL, and ORL using structural OCT were conducted both before the surgery and one month after the surgical procedure. Importantly, a control group comprising 14 healthy eyes, matched for age and significant refractive error (<3.00 diopters), was included in the current analysis. RESULTS: Our analysis indicated no significant disparity before and after surgery in terms of best-corrected visual acuity (BCVA), RNFL, IRL, and ORL. Conversely, concerning the macular ganglion cell layer-inner plexiform layer analysis, a substantial increase in mGCL-IPL was observed following the surgical intervention. The mean mGCL-IPL measured 60.8 ± 9.2 µm at baseline and 66.1 ± 13.2 µm one month after the surgery (p = 0.026). Notably, comparison between the strabismus group at baseline and the healthy group revealed a significant reduction in mGCL-IPL in the strabismus group (60.8 ± 9.2) compared to the healthy control group (68.3 ± 7.2; p = 0.014). CONCLUSIONS: Following strabismus surgery, our observations pointed towards a thickening of the mGCL-IPL layer, which is likely attributable to transient local inflammation. Additionally, we identified a significant differentiation in the mGCL-IPL complex between the pediatric patient group with strabismus and the control group.

Structural OCT and OCT angiography biomarkers associated with the development and progression of geographic atrophy in AMD.

BACKGROUND: Geographic atrophy (GA) is an advanced, irreversible, and progressive form of age-related macular degeneration (AMD). Structural optical coherence tomography (OCT) and OCT angiography (OCTA) have been largely used to characterize this stage of AMD and, more importantly, to define biomarkers associated with the development and progression of GA in AMD. METHODS: Articles pertaining to OCT and OCTA biomarkers related to the development and progression of GA with relevant key words were used to search in PubMed, Researchgate, and Google Scholar. The articles were selected based on their relevance, reliability, publication year, published journal, and accessibility. RESULTS: Previous reports have highlighted various OCT and OCTA biomarkers linked to the onset and advancement of GA. These biomarkers encompass characteristics such as the size, volume, and subtype of drusen, the presence of hyperreflective foci, basal laminar deposits, incomplete retinal pigment epithelium and outer retinal atrophy (iRORA), persistent choroidal hypertransmission defects, and the existence of subretinal drusenoid deposits (also referred to as reticular pseudodrusen). Moreover, biomarkers associated with the progression of GA include thinning of the outer retina, photoreceptor degradation, the distance between retinal pigment epithelium and Bruch's membrane, and choriocapillaris loss. CONCLUSION: The advent of novel treatment strategies for GA underscores the heightened need for prompt diagnosis and precise monitoring of individuals with this condition. The utilization of structural OCT and OCTA becomes essential for identifying distinct biomarkers associated with the initiation and progression of GA.

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.

Validation of a deep learning model for automatic detection and quantification of five OCT critical retinal features associated with neovascular age-related macular degeneration.

PURPOSE: To develop and validate a deep learning model for the segmentation of five retinal biomarkers associated with neovascular age-related macular degeneration (nAMD). METHODS: 300 optical coherence tomography volumes from subject eyes with nAMD were collected. Images were manually segmented for the presence of five crucial nAMD features: intraretinal fluid, subretinal fluid, subretinal hyperreflective material, drusen/drusenoid pigment epithelium detachment (PED) and neovascular PED. A deep learning architecture based on a U-Net was trained to perform automatic segmentation of these retinal biomarkers and evaluated on the sequestered data. The main outcome measures were receiver operating characteristic curves for detection, summarised using the area under the curves (AUCs) both on a per slice and per volume basis, correlation score, enface topography overlap (reported as two-dimensional (2D) correlation score) and Dice coefficients. RESULTS: The model obtained a mean (±SD) AUC of 0.93 (±0.04) per slice and 0.88 (±0.07) per volume for fluid detection. The correlation score (R2) between automatic and manual segmentation obtained by the model resulted in a mean (±SD) of 0.89 (±0.05). The mean (±SD) 2D correlation score was 0.69 (±0.04). The mean (±SD) Dice score resulted in 0.61 (±0.10). CONCLUSIONS: We present a fully automated segmentation model for five features related to nAMD that performs at the level of experienced graders. The application of this model will open opportunities for the study of morphological changes and treatment efficacy in real-world settings. Furthermore, it can facilitate structured reporting in the clinic and reduce subjectivity in clinicians' assessments.

Distinct Pathways of Macular Atrophy in Type 3 Macular Neovascularization Associated With AMD.

Purpose: To explore the occurrence of macular atrophy (MA) in eyes with age-related macular degeneration (AMD)-associated Type 3 macular neovascularization (MNV) treated with anti-vascular endothelial growth factor (anti-VEGF) therapy. Importantly, we aimed at describing the existence of separate pathways leading to MA. Methods: We analyzed 41 participants (41 eyes) with treatment-naïve Type 3 MNV who were followed up for a duration of 12 months after beginning the anti-VEGF therapy. At the one-year follow-up visit, optical coherence tomography (OCT) scans were reviewed for the presence of MA. MA regions of interest (ROIs) were selected and traced back to their original dominant baseline lesion (i.e., precursor) through previous serially captured OCT scans. Baseline lesions included precursors associated with the development and exudation of MNV and causes external to the neovascularization itself. Results: At the one-year follow-up visit, MA was graded to be present in 38 (92.7%) out of 41 eyes. These 78 MA ROIs were divided into two subgroups according to the precursor lesion, yielding a group of 53 MA lesions with precursors associated with the development and exudation of MNV (i.e., MA caused by physical harm from Type 3 neovessels, collapse of a serous pigment epithelium detachment, and fibrosis) and 25 MA regions with precursors external to the neovascularization itself (i.e., MA caused by drusen or subretinal drusenoid deposits). Conclusions: Eyes with Type 3 MNV are commonly complicated by MA and precursors of MA include causes associated with the development and exudation of MNV, as well as lesions unrelated to the neovascularization process itself.

Platelet rich plasma for primary macular hole: A case series.

OBJECTIVE: To evaluate the anatomical and functional macular results and rate of complications following surgical treatment of primary macular hole (MH) with autologous platelet rich plasma (a-PRP) use. DESIGN: retrospective, interventional, non-randomized case series. PARTECIPANTS AND METHODS: A cohort of 9 consecutive patients from January 1, 2019 to August 31, 2021 who underwent vitrectomy with a-PRP use for primary MH were included. Anatomical results based on spectral domain- optical coherence tomography (SD-OCT) and visual acuity were analyzed. RESULTS: 10 pseudophakic eye of 9 patients were enrolled. Six patients were female and three patients were male. The mean age was 69.9 years ± 1.48. The baseline MH minimum diameter was 486.1 µm ± 37.1, and mean pre operative best-corrected visual acuity (BCVA) was 0.91 ± 0.03 logMAR (Snellen equivalent 20/160). Mean 1 month post operative BCVA was 0.81 ± 0.57 logMAR (Snellen equivalent 20/130; p = 1.000); mean 3 month post operative BCVA was 0.66 ± 0.04 logMAR (Snellen equivalent 20/90; p = 0.006); mean 6 month post operative BCVA was 0.6 ± 0.04 logMAR (Snellen equivalent 20/80; p < 0.001). In all eyes, 10/10 (100%), there was a complete MH closure at 6 months follow up: 5 eyes (50%) with a U-type closure pattern, 4 eyes (40%) with a V-type pattern and 1 eye (10%) with an irregular foveal contour closure at 6 month follow-up. No ocular and systemic complications were reported. CONCLUSION: The a-PRP use is a successful and promising vitreoretinal surgical technique option for primary MH.

Pitchfork sign following pars Plana vitrectomy for idiopathic epiretinal membrane: A case report.

PURPOSE: To report a case of pitchfork sign following pars plana vitrectomy for idiopathic epiretinal membrane. STUDY DESIGN: Case report. RESULTS: A 75-year-old man was referred to the surgical retina service due to a quantitative and qualitative decline in vision in the left eye (LE) for several months. Optical coherence tomography (OCT) examination revealed the presence of a stage III epiretinal membrane (ERM) according to the Govetto classification. Seven days after undergoing a 25-gauge pars plana vitrectomy (PPV) with ERM peeling and balanced salt solution (BSS) tamponade, OCT examination revealed the presence of the 'pitchfork sign' in the macular region, along with the detection of a choroidal neovascularization (CNV) through OCT-A examination. After receiving two monthly intravitreal anti-VEGF injections, a complete regression of the MNV was observed. CONCLUSIONS: We reported, for the first time, the iatrogenic onset of the pitchfork sign following vitreoretinal surgery. This discovery highlights the unique presentation of the pitchfork sign in the context of surgical procedures, expanding our comprehension of its range of causes.

OCT risk factors for 2-year foveal involvement in non-treated eyes with extrafoveal geographic atrophy and AMD.

PURPOSE: To assess the relationship of optical coherence tomography (OCT) findings and progression to foveal atrophy in a cohort of eyes with extrafoveal geographic atrophy (GA) and age-related macular degeneration (AMD) at inclusion. METHODS: We retrospectively analyzed 45 participants (45 eyes) with extrafoveal GA at baseline and with 2 years of regular follow-ups. Several OCT qualitative features (i.e., presence of foveal flat pigment epithelium detachment with a thin double layer sign [DLS] and reticular pseudodrusen, GA focality) and quantitative measurements (outer retinal layer thickness, retinal pigment epithelium [RPE] to Bruch's membrane [BM] volume, minimum distance from the central foveal circle, and untransformed GA lesion size area) were assessed at baseline. Logistic regression analyses were carried out to identify independent significant predictors and compute odds ratios (ORs) for the risk of the development of atrophy. RESULTS: At month 24, 26 eyes (57.8%) developed atrophy in the foveal central circle, while 11 eyes (24.4%) developed atrophy in the foveal central point. Significant independent predictive features for the development of atrophy in the foveal central circle included foveal outer retinal thickness (OR, 0.867; p = 0.015), minimum distance from the foveal central circle (OR, 0.992; p = 0.022), and foveal thin DLS (OR, 0.044; p = 0.036). The only independent predictive feature for the development of atrophy in the foveal central point was the presence of foveal thin DLS (OR, 0.138; p = 0.017). CONCLUSIONS: We identified OCT risk factors for 2-year foveal atrophy in eyes with untreated extrafoveal GA at baseline.

Multimodal Imaging of a novel MFSD8/CLN7 mutation associated with non-syndromic symmetric adult-onset macular dystrophy.

PURPOSE: To report multimodal imaging features of a novel MFSD8/CLN7 pathogenic variant associated with bilateral and symmetric non-syndromic macular dystrophy. METHODS: A 63-year-old female patient presented complaining of a gradual subjective decline in visual acuity in both eyes over the previous months. This patient underwent a comprehensive ophthalmological assessment, including multimodal retinal imaging and electrophysiological testing. Given suspicion for a hereditary retinal disorder, genetic testing was pursued. RESULTS: The eye examination revealed blunted foveal reflexes and no lesions or abnormalities in the equatorial or anterior retinal periphery. Multimodal imaging showed a bilateral and almost symmetrical subfoveal interruption of the outer retinal layers including an optical gap. Genetic testing revealed that the MFSD8/CLN7 gene exhibited a homozygous variant, specifically p.Ala484Val (c.1451C>T). This variant was identified as the likely causative factor for the condition. CONCLUSION: We herein describe the clinical findings of a previously unreported homozygous variant in the MFSD8/CLN7 gene, resulting in a non-syndromic form of bilateral central macular dystrophy.

Relationship of Topographic Distribution of Macular Atrophy Secondary to Neovascular AMD and Reading Performance.

Purpose: The purpose of this study was to provide a topographical assessment of macular atrophy in successfully treated neovascular age-related macular degeneration (AMD) eyes to investigate determinants of monocular reading performance. Methods: A total of 60 participants (60 eyes) with previously treated neovascular AMD and absence of optical coherence tomography (OCT) signs of exudation were enrolled. Reading performance was assessed monocularly using Radner charts. The following variables were obtained: (i) the reading acuity was defined as the logarithm of the reading acuity determination (LogRAD), at the smallest sentence, a patient is able to read in less than 30 seconds; (ii) the maximum reading speed was defined as the fastest time achieved and is calculated in words per minute (wpm). OCT images were reviewed for the presence of macular atrophy within the central, 4 inner and 4 outer Early Treatment Diabetic Retinopathy Study (ETDRS) grid subfields. Contributory factors affecting reading performance were examined using univariable and multivariable linear mixed model considering reading acuity and reading speed as dependent variables. Results: Median (interquartile range [IQR]) values were 0.53 (IQR = 0.17) LogRAD for reading acuity, and 144 (60) wpm for maximum reading speed. Thirty-five out of 60 (58.3%) eyes were characterized by the presence of macular atrophy. In multiple regression analysis, reading acuity was significantly associated with presence of macular atrophy in the foveal central circle (P = 0.024). Conversely, the maximum reading speed was associated with presence of macular atrophy in the inner-right ETDRS subfield (P = 0.005). Conclusions: We showed a significant relationship between presence and location of macular atrophy and reading performance in neovascular AMD.

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.

Platelet concentrates in macular hole surgery. A journey through the labyrinth of terminology, preparation, and application: a comprehensive review.

The surgical management of macular holes is undergoing continuous evolution, with recent focus on the utilization of platelet concentrates as a promising adjunctive intervention. Currently, they present a valid surgical approach for achieving anatomical and functional success with a non-inferiority comparably to the alternative surgical techniques. Nonetheless, the utilization of varied platelet concentrates terminologies, coupled with the lack of standardization in their preparation methodologies, engenders both lexical confusion and challenges in comparing scientific studies published up until now. In this review, we summarized the published evidence concerning the application of platelet concentrates in macular holes surgery, aiming to clarify the terminology and methodologies employed and to establish a common consensus facilitating further development and diffusion of this promising technique.

Sectorial Ganglion Cell Complex Thickness as Biomarker of Vision Outcome in Patients With Dominant Optic Atrophy.

Purpose: Dominant optic atrophy (DOA) is an inherited condition caused by autosomal dominant mutations involving the OPA-1 gene. The aim of this study was to assess the relationship between macular ganglion cell and inner plexiform layer (GC-IPL) thickness obtained from structural optical coherence tomography (OCT) and visual outcomes in DOA patients. Methods: The study recruited 33 patients with confirmed OPA-1 heterozygous mutation and DOA. OCT scans were conducted to measure the GC-IPL thickness. The average and sectorial Early Treatment Diabetic Retinopathy Study (ETDRS) charts (six-sector macular analysis to enhance the topographical analysis) centered on the fovea were considered. Several regression analyses were carried out to investigate the associations between OCT metrics and final best-corrected visual acuity (BCVA) as the dependent variable. Results: The mean BCVA was 0.43 ± 0.37 logMAR, and the average macular GC-IPL thickness was 43.65 ± 12.56 µm. All of the GC-IPL sectors were significantly reduced and correlated with BCVA. The univariate linear regression and the multivariate stepwise regression modeling showed that the strongest association with final BCVA was observed with the internal superior GC-IPL thickness. Dividing patients based on BCVA, we found a specific pattern. Specifically, in patients with BCVA ≤ 0.3 logMAR, the external superior and inferior sectors together with the internal superior were more significant; whereas, for BCVA > 0.3 logMAR, the external superior sector and internal superior sector were more significant. Conclusions: The study identified OCT biomarkers associated with visual outcomes in DOA patients. Moreover, we assessed a specific OCT biomarker for DOA progression, ranging from patients in the early stages of disease with more preserved GC-IPL sectorial thickness to advanced stages with severe thinning.

INTERSESSION REPEATABILITY OF READING PERFORMANCE MEASURES IN PATIENTS WITH NEOVASCULAR AGE-RELATED MACULAR DEGENERATION.

PURPOSE: To assess the intersession repeatability of reading performance measures in patients with previously treated neovascular age-related macular degeneration and good best-corrected visual acuity (≥20/40 Snellen). METHODS: Ninety-one patients (91 eyes) with a diagnosis of previously treated neovascular age-related macular degeneration and good best-corrected visual acuity (≥20/40 Snellen) were prospectively enrolled. Reading performance metrics were assessed using Radner charts, and these measurements were repeated after 7 days to obtain the intersession repeatability. To test repeatability, we calculated the intraclass correlation coefficient, the 95% coefficient of repeatability, and the coefficient of variation for each reading parameter: 1) reading acuity (RA-LogRAD); 2) maximal reading speed-words per minute; 3) RA score (RA score-LogRAD); and 4) critical print size-LogRAD. RESULTS: Mean ± standard deviation best-corrected visual acuity was 0.13 ± 0.01 logMAR [range: 0.00-0.30 logMAR]. The intraclass correlation coefficient values indicated a good reliability for all the analyzed metrics (0.901 for RA; 0.859 for max reading speed; 0.906 for RA score; and 0.868 for critical print size). The coefficient of repeatability was 0.2 LogRAD for RA, 63.2 words per minute for max reading speed, 0.2 LogRAD for RA score, and 0.2 LogRAD for critical print size. Coefficient of variation was 5.5% for RA, 8.9% for max reading speed, 5.8% for RA score, and 6.9% for critical print size. CONCLUSION: Reading performance metrics are characterized by good values of intersession repeatability in patients with neovascular age-related macular degeneration with good best-corrected visual acuity. Our findings may grant the employment of such measures in trials assessing the visual outcome in these patients.

Ocular Surface Disease in Patients With Atopic Dermatitis Treated With Dupilumab: A Prospective Case-Control Study.

PURPOSE: The aim of this study was to evaluate the variation of dry eye disease (DED) prevalence in patients with atopic dermatitis (AD) treated with dupilumab. METHODS: This prospective case-control study included consecutive patients with moderate-to-severe AD scheduled for dupilumab between May and December 2021 and healthy subjects. DED prevalence, the Ocular Surface Disease Index, tear film breakup time test, osmolarity, Oxford staining score, and Schirmer test results were collected at baseline, 1 month, and 6 months after dupilumab therapy. The Eczema Area and Severity Index was assessed at baseline. Ocular side effects and discontinuation of dupilumab were also recorded. RESULTS: Seventy-two eyes from 36 patients with AD treated with dupilumab and 36 healthy controls were included. Prevalence of DED increased from 16.7% at baseline to 33.3% at 6 months in the dupilumab group ( P = 0.001), whereas it remained unchanged in the control group ( P = 0.110). At 6 months, the Ocular Surface Disease Index and Oxford score increased (from 8.5 ± 9.8 to 11.0 ± 13.0, P = 0.068, and from 0.1 ± 0.5 to 0.3 ± 0.6, P = 0.050, respectively), the tear film breakup time test and Schirmer test results decreased (from 7.8 ± 2.6 s to 7.1 ± 2.7 s, P < 0.001, and from 15.4 ± 9.6 mm to 13.2 ± 7.9 mm, P = 0.036, respectively) in the dupilumab group, whereas they remained stable in the control group ( P > 0.05). Osmolarity was unchanged (dupilumab P = 0.987 and controls P = 0.073). At 6 months after dupilumab therapy, 42% of patients had conjunctivitis, 36% blepharitis, and 2.8% keratitis. No severe side effects were reported, and none of the patients discontinued dupilumab. No association between Eczema Area and Severity Index and DED prevalence was shown. CONCLUSIONS: DED prevalence increased in patients with AD treated with dupilumab at 6 months. However, no severe ocular side effects were found and no patient discontinued therapy.

Deep-learning based automated quantification of critical optical coherence tomography features in neovascular age-related macular degeneration.

PURPOSE: To validate a deep learning algorithm for automated intraretinal fluid (IRF), subretinal fluid (SRF) and neovascular pigment epithelium detachment (nPED) segmentations in neovascular age-related macular degeneration (nAMD). METHODS: In this IRB-approved study, optical coherence tomography (OCT) data from 50 patients (50 eyes) with exudative nAMD were retrospectively analysed. Two models, A1 and A2, were created based on gradings from two masked readers, R1 and R2. Area under the curve (AUC) values gauged detection performance, and quantification between readers and models was evaluated using Dice and correlation (R2) coefficients. RESULTS: The deep learning-based algorithms had high accuracies for all fluid types between all models and readers: per B-scan IRF AUCs were 0.953, 0.932, 0.990, 0.942 for comparisons A1-R1, A1-R2, A2-R1 and A2-R2, respectively; SRF AUCs were 0.984, 0.974, 0.987, 0.979; and nPED AUCs were 0.963, 0.969, 0.961 and 0.966. Similarly, the R2 coefficients for IRF were 0.973, 0.974, 0.889 and 0.973; SRF were 0.928, 0.964, 0.965 and 0.998; and nPED were 0.908, 0.952, 0.839 and 0.905. The Dice coefficients for IRF averaged 0.702, 0.667, 0.649 and 0.631; for SRF were 0.699, 0.651, 0.692 and 0.701; and for nPED were 0.636, 0.703, 0.719 and 0.775. In an inter-observer comparison between manual readers R1 and R2, the R2 coefficient was 0.968 for IRF, 0.960 for SRF, and 0.906 for nPED, with Dice coefficients of 0.692, 0.660 and 0.784 for the same features. CONCLUSIONS: Our deep learning-based method applied on nAMD can segment critical OCT features with performance akin to manual grading.

Peripapillary hyperreflective ovoid mass-like structures (PHOMS) in patients with acute Leber's hereditary optic neuropathy.

PURPOSE: Peripapillary hyperreflective ovoid mass-like structures (PHOMS) represent an optical coherence tomography (OCT) finding that has been characterized in different forms of pseudopapilledema. The aim of this study was to investigate the prevalence of PHOMS in patients affected by acute LHON using structural OCT, and to provide a detailed description of these findings. METHODS: Patients with a clinical and molecularly confirmed diagnosis of acute LHON (visual loss having occurred less than 6 months) were enrolled from the neuro-ophthalmology clinic at San Raffaele Scientific Institute. Patients had a complete ophthalmologic evaluation, including imaging with structural OCT. RESULTS: Our analysis included 16 patients (21 eyes-8 males and 8 females) with acute LHON. Structural OCT exhibited PHOMS in 12 eyes from 9 patients with a prevalence rate of 57.1%. In a subsequent topographical assessment in the peripapillary area, the most common location of PHOMS was the temporal region (12 out of 12 eyes), while the nasal region was affected in 2 eyes (16.7%). Considering the 12 eyes with PHOMS, mean ± SD temporal peripapillary RNFL thickness was 87.5 ± 28.4 microns. The temporal peripapillary RNFL thickness was significantly lower in eyes without PHOMS (63.7 ± 32.2 microns; P = 0.40). At the 12-month follow-up visit, PHOMS disappeared in 10 out of 12 eyes. CONCLUSIONS: Acute LHON eyes have PHOMS which are mainly confined to the temporal peripapillary sector. PHOMS may represent swelled retinal fibers that have herniated or are in stasis.