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.

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.

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.

PREVALENCE AND MORPHOLOGIC BIOMARKERS OF METAMORPHOPSIA IN EYES WITH "RESOLVED" CHRONIC CENTRAL SEROUS CHORIORETINOPATHY.

PURPOSE: To assess relationships between demographics, clinical characteristics, and optical coherence tomography characteristics with persistence of metamorphopsia after resolution of subretinal fluid in eyes with chronic central serous chorioretinopathy. METHODS: One-hundred participants with "resolved" (absence of subretinal fluid) chronic central serous chorioretinopathy were retrospectively analyzed. Patients underwent a complete ophthalmologic evaluation, including assessment of the presence of metamorphopsia. At the study visit, optical coherence tomography scans were reviewed for qualitative and quantitative features. RESULTS: Sixty-six of 100 patients (66.0%) complained of metamorphopsia. Both the foveal and parafoveal ganglion cell complex thicknesses were thinner in central serous chorioretinopathy eyes with metamorphopsia (35.1 ± 10.6 µ m and 82.0 ± 18.1 µ m vs. 40.7 ± 11.8 µ m and 93.1 ± 13.5 µ m, P = 0.030 and P < 0.0001). In the foveal region, the outer plexiform layer and outer nuclear layer thicknesses were thinner in patients with metamorphopsia (24.6 ± 8.5 µ m and 63.1 ± 20.9 µ m vs. 29.1 ± 8.7 and 76.2 ± 18.2 µ m, P = 0.016 and P = 0.005). The ellipsoid zone band was more frequently discontinued in eyes with metamorphopsia (56.1% vs. 35.3%, P = 0.039). Multivariate stepwise linear regression analysis demonstrated that the strongest associations with the presence of metamorphopsia were with parafoveal ganglion cell complex thickness ( P = 0.004), foveal outer nuclear layer thickness ( P = 0.010), and number of previous recurrences of subretinal fluid accumulation ( P = 0.017). The time interval from the last subretinal fluid resolution was not associated with the presence of metamorphopsia. CONCLUSION: In "resolved" central serous chorioretinopathy, clinical aspects (i.e., number of previous recurrences) and structural changes (i.e., ganglion cell complex and outer nuclear layer thinning) are associated with metamorphopsia after subretinal fluid resolution.

FUNDUS AUTOFLUORESCENCE IN EXTENSIVE MACULAR ATROPHY WITH PSEUDODRUSEN AND DIFFUSE TRICKLING GEOGRAPHIC ATROPHY.

PURPOSE: To establish whether extensive macular atrophy with pseudodrusen (EMAP) can be distinguished from the diffuse-trickling phenotype of geographic atrophy (DTGA) secondary to age-related macular degeneration on the basis of its features on blue-light autofluorescence. METHODS: The authors reviewed our prospectively maintained database to enroll patients with a diagnosis of EMAP, DTGA, and non-DTGA with a minimum follow-up of 1 year. Atrophic areas and growth rates were measured on blue-light autofluorescence images, using the Heidelberg Region Finder tool. Circularity and roundness were chosen as atrophy shape descriptors, extracted using ImageJ, and compared between disease groups. RESULTS: A total of 28 EMAP, 27 DTGA, and 30 non-DTGA eyes were included in the analysis. The median follow-up time was around 3.5 years. Extensive macular atrophy with pseudodrusen was characterized by an irregular and elongated shape (low circularity and low roundness) and associated with a fast atrophy growth rate (3.6 mm 2 /year), compared with non-DTGA. However, these parameters were not significantly different between EMAP and DTGA. CONCLUSION: Our study found that EMAP and DTGA cannot be effectively differentiated on fundus autofluorescence. In both diseases, the macular atrophic area has a major vertical axis, fringed borders, and fast progression.

HYPERREFLECTIVE BAND IN THE GANGLION CELL LAYER IN RETINITIS PIGMENTOSA.

PURPOSE: To describe a sign that takes the form of a continuous hyperreflective band within the thickness of the ganglion cell layer (GCL), thus dubbed the "hyperreflective ganglion cell layer band" (HGB), which the authors detected in a fraction of patients affected by retinitis pigmentosa (RP). METHODS: Retrospective, cross-sectional, observational study. Optical coherence tomography (OCT) images of patients with RP examined between May 2015 and June 2021 were retrospectively reviewed for the presence of HGB, epiretinal membrane (ERM), macular hole, and cystoid macular edema (CME). The ellipsoid zone (EZ) width was also measured. A subgroup of patients underwent microperimetry in the central 2°, 4°, and 10°. RESULTS: One hundred and fifty-four eyes from 77 subjects were included in the study. The HGB was present in 39 (25.3%) eyes with RP. Mean best-corrected visual acuity (BCVA) was 0.39 ± 0.05 logMAR (approximately 20/50 Snellen equivalent) and 0.18 ± 0.03 logMAR (approximately 20/32 Snellen equivalent) in eyes with and without HGB, respectively ( P < 0.001). The two groups did not differ regarding EZ width; mean 2°, 4°, and 10° retinal sensitivity; and prevalence of CME, ERM, and macular hole. The multivariable analysis showed the presence of HGB to be a predictor of poorer BCVA ( P < 0.001). CONCLUSION: HGB is an OCT finding detectable in approximately a quarter of eyes with RP and is associated with a poorer visual function. In the discussion, the authors speculate about possible morphogenetic scenarios to explain this observation.

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.

No difference in clinical outcomes between functionally aligned cruciate-retaining and posterior-stabilized robotic-assisted total knee arthroplasty.

PURPOSE: To compare the clinical outcomes of subjects undergoing primary robotic-assisted total knee arthroplasty (RA-TKA), following functional alignment (FA) principles, with cruciate-retaining (CR) or posterior-stabilized (PS) bearing designs, at a minimum of 24 months of follow-up. METHODS: This observational, retrospective study included 167 consecutive patients undergoing RA-TKA with cemented PS and cementless CR implants performed with a CT-base robotic-arm assisted system (Mako, Stryker), following FA principles, between 2017 and 2020. Patients were followed up with a clinical and radiographic assessment and were administered the Forgotten Joint Score-12 (FJS-12), Knee Injury and Osteoarthritis Outcome Score for Joint Replacement (KOOS-JR), and the 5-level Likert scale (5-LLS). RESULTS: Three TKA revisions were performed (2 PS, 1 CR); therefore, a total of 164 knees with a mean age of 71.7 years (SD 8.9) were considered (80 cemented PS; 84 cementless CR). No statistically significant differences were recorded between study groups relative to FJS-12, KOOS-JR, and 5-LLS at a minimum of two year follow-up (FJS-12 89.3 ± 9.2 vs 87.5 ± 12.8, p-value 0.46; KOOS-JR 88.8 ± 10.0 vs 86.7 ± 14.0, p-value 0.31; 5-LLS 4.5 ± 0.7 vs 4.5 ± 0.8, p-value 0.34). CONCLUSION: No significant outcome differences were reported between patients undergoing PS and CR RA-TKA at a minimum of two year follow-up. RA-TKA achieves excellent clinical results and high satisfaction scores, regardless of the implant design used.

Intermediate- and long-term oncological outcomes of active surveillance for localized renal masses: a systematic review and quantitative analysis.

OBJECTIVE: To evaluate intermediate- and long-term oncological outcomes of active surveillance (AS) for localized renal masses (LRMs). METHODS: This systematic literature review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement and registered on PROSPERO (CRD42021230416). Studies on AS for LRMs with at least 3 years' follow-up were eligible. Two review authors independently screened the literature, extracted data, and assessed risk of bias. The primary outcomes were metastasis rate, renal cell carcinoma (RCC)-specific mortality (RCC-SM) and all-cause mortality (ACM). Pooled estimates were obtained from random-effects models. Subgroup analyses were performed for small renal masses (SRMs; ≤4 cm) and non-SRMs (>4 cm). RESULTS: We analysed 18 unique cohorts comprising 2066 patients. The pooled initial maximum tumour size was 2.8 cm (95% confidence interval [CI] 2.7-3.0) and the percutaneous biopsy rate was 28%. The pooled mean annual growth rate was 2.8 mm (95% CI 2.1-3.4). Within a pooled mean follow-up of 53 months, 2.1% (95% CI 1.0-3.6) of patients developed metastatic disease, 1.0% (95% CI 0.3-2.1) died from RCC and 22.6% (95% CI 15.8-30.2) died from any cause. For patients with SRMs (nine studies, n = 987), the pooled metastasis rate was 1.8% (95% CI 0.5-3.7), RCC-SM was 0.6% (95% CI 0-2.1), and ACM was 28.5% (95% CI 17.4-41.4). Across five studies reporting on outcomes of 239 patients with non-SRMs, the pooled metastasis rate was 5.1% (95% CI 0-17.3), RCC-SM was 2.1% (95% CI 0-8.9) and ACM was 29.1% (95% CI 13.6-47.3). This review is limited by non-standardized inclusion criteria, definitions and follow-up, data heterogeneity, limited patient numbers in sub-analyses and absence of high-quality studies. CONCLUSIONS: Active surveillance is a safe intermediate- and long-term management option for well-selected patients with LRMs, especially those with SRMs. Limited data are available for non-SRMs, but current evidence would support further evaluation of this approach in selected patients. It is not possible to draw definitive conclusions until more high-quality data become available.

Contrast-enhanced ultrasound (CEUS) imaging for active surveillance of small renal masses.

PURPOSE: To assess the safety and efficacy of contrast-enhanced ultrasound (CEUS) imaging for monitoring small (< 4 cm) renal masses (SRM) in patients undergoing active surveillance (AS). METHODS: We retrospectively selected all consecutive patients with SRMs who underwent AS for at least 6 months at our Institution between January 2014 and December 2018. CEUS imaging was performed by two experienced genitourinary radiologists at established time points. The accuracy of CEUS for monitoring SRM size was compared with that of CT scan. For solid SRMs, four enhancement patterns (EP) were recorded. Radiological progression was defined as SRM growth rate ≥ 5 mm/year. RESULTS: Overall, 158/1049 (15.1%) patients with SRMs underwent AS. At a median follow-up of 25 months (IQR 13-39), no patient died due to renal cell carcinoma (RCC). No patients experienced CEUS-related adverse events. There was a large variability in the pattern of growth of SRMs (overall median growth rate: 0.40 mm/year), with 9.5% of SRMs showing radiological progression. The median SRM size was comparable between CEUS and CT scan examinations at all time points. The vast majority (92.7%) of SRMs did not show a change in their EP over time; and there was no association between the SRM's EP and radiological progression or SRM size. Overall, 43 (27.2%) patients underwent delayed intervention (DI); median SRM size, and median growth rate were significantly higher in these patients as compared to those continuing AS. CONCLUSION: In experienced hands, CEUS is a safe and effective strategy for active monitoring of SRMs in well-selected patients undergoing AS.

Rate and associations of inner retinal thinning in eyes with retinal vein occlusion and regressed macular oedema.

PURPOSE: To investigate the associations between visual acuity (VA) and structural optical coherence tomography (OCT) features in retinal vein occlusion (RVO) eyes after cystoid macular oedema (CMO) regression and to assess whether inner retinal thinning is progressive. METHODS: Retrospective observational study of RVO eyes with regressed CMO for at least 6 months. OCT scans at CMO regression were analysed, and features were correlated with VA at that visit. The inner retinal thickness was longitudinally compared between RVO and unaffected fellow eyes (controls) with linear mixed models. The rate of inner retinal thinning was obtained as the interaction term between disease status and time. Associations between inner retinal thinning and clinical characteristics were explored. RESULTS: Thirty-six RVO eyes were followed for 34.2 ± 21.1 months after CMO regression. The presence of ellipsoid zone disruption (regression estimate[standard error(SE)] = 0.16[0.04] LogMAR vs. intact, p < 0.001) and lower inner retinal thickness (regression estimate[SE] = -0.25[0.12] LogMAR for 100-µm increase, p = 0.01) were associated with worse VA. The inner retinal thickness decreased faster in RVO than controls (rate of retinal thinning -0.27 ± 0.09 µm/month vs. -0.08 ± 0.11 µm/month, p = 0.01). Macular ischaemia was associated with a faster rate of retinal thinning (interaction term macular ischaemia*follow-up time, p = 0.04). CONCLUSION: Inner retinal and photoreceptors' layers integrity are associated with better visual acuity once CMO resolves. RVO eyes undergo progressive inner retinal thinning after CMO regression, faster in eyes with macular ischaemia.

New insights in the multimodal imaging of retinitis pigmentosa.

Retinitis pigmentosa (RP) is a group of inherited rod-cone dystrophies, noted for a high genotypical and phenotypical heterogeneity.Traditionally, VA, visual field, and electroretinography have been used to assess RP progression. However, visual acuity and visual field tests are essentially subjective and, especially in the late stages of the disease, are unable to confidently reveal minor progression. Therefore, there is a need for novel examination modalities that rely on quantitative, structural measurements. In this regard, several non-invasive imaging techniques have been studied, including spectral-domain optical coherence tomography, optical coherence tomography angiography, and fundus autofluorescence. By correlating surrogate biomarkers with functional measurements of the disease, these techniques may be able to develop reliable outcome meters that can be used to gain a deeper understanding of the underlying causes of the disease and to assess the effectiveness of therapy even before an actual loss of vision occurs.In this review, we will summarize the recent imaging findings and biomarkers that have been identified in RP patients. Our goal is to provide information that can promptly aid in selecting patients for clinical trials and new gene therapies, monitoring the disease progression, and evaluating treatment outcomes.

Multimodal imaging in Best Vitelliform Macular Dystrophy: Literature review and novel insights.

Best Vitelliform Macular Dystrophy (BVMD) is a dominantly inherited retinal disease caused by dominant variants in the BEST1 gene. The original classification of BVMD is based on biomicroscopy and color fundus photography (CFP); however, advancements in retinal imaging provided unique structural, vascular, and functional data and novel insights on disease pathogenesis. Quantitative fundus autofluorescence studies informed us that lipofuscin accumulation, the hallmark of BVMD, is unlikely to be a primary effect of the genetic defect. It could be due to a lack of apposition between photoreceptors and retinal pigment epithelium in the macula with subsequent accumulation of shed outer segments over time. Optical Coherence Tomography (OCT) and adaptive optics imaging revealed that vitelliform lesions are characterized by progressive changes in the cone mosaic corresponding to a thinning of the outer nuclear layer and then disruption of the ellipsoid zone, which are associated with a decreased sensitivity and visual acuity. Therefore, an OCT staging system based on lesion composition, thus reflecting disease evolution, has been recently developed. Lastly, the emerging role of OCT Angiography proved a greater prevalence of macular neovascularization, the majority of which are non-exudative and develop in late disease stages. In conclusion, effective diagnosis, staging, and clinical management of BVMD will likely require a deep understanding of the multimodal imaging features of this disease.

Multimodal Imaging of Vitreo-Retinal Lymphoma: A Comprehensive Review.

PURPOSE: Vitreoretinal lymphoma (VRL) is a rare lymphoma affecting the vitreous and the retina. Clinical diagnosis is challenging and often delayed and may lead to aggravated prognosis. This study aims to review multimodal imaging findings in VRL. METHODS: We performed a comprehensive narrative review of the multimodal imaging findings that might be useful in the detection of VRL lesions. RESULTS: The most frequent ocular manifestations of VRL are vitritis, and retinal and sub-retinal Pigmented Epithelium (RPE) infiltrations. Color Fundus Photography (CFP) detects vitreous haze, optic nerve, retinal and sub-RPE infiltration. Ultra-wide field imaging allows visualization of different patterns of vitreous haze and monitoring of VRL evolution through the detection of chorio-retinal atrophy (CRA). Fundus Autofluorescence shows granular hypo- and hyper-autofluorescent pattern. Optical Coherence Tomography (OCT) reveals vitreous cells, vertical hyper-reflective lesions and sub-RPE infiltrates. Fluorescein Angiography (FA) shows hypo or hyperfluorescent round lesions at the late stages of the examination, while Indocyanine Green Angiography (ICGA) detects round areas of focal hypo-fluorescence in the early phases that gradually enlarge in the late phases. B-scan ultrasonography detects vitreous opacities and homogeneous hyperreflective corpuscular material in the vitreous, and is a strongly recommended tool in suspecting VRL and is particularly useful when vitreous haze is impeding retinal examination. CONCLUSION: Diagnostic vitrectomy with cytopathological analysis remains the gold standard for VRL diagnosis, however multimodal imaging allows the identification of suggestive retinal and vitreal lesions for early suspicion, diagnosis, and treatment and monitoring disease progression and response to treatment.

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.

Optical coherence tomography (OCT) and OCT-angiography in syndromic versus non-syndromic USH2A-associated retinopathy.

PURPOSE: To compare non-syndromic and syndromic forms of USH2A-related retinitis pigmentosa (RP) by means of structural optical coherence tomography (OCT) and OCT-angiography (OCTA). METHODS: Observational, cross-sectional, multicenter study. All patients underwent best corrected visual acuity (BCVA) measurement, OCT (Spectralis HRA + OCT, Heidelberg Engineering) and OCTA (OCT DRI Topcon Triton, Topcon Corporation). We compared subfoveal choroidal thickness (SCT), choroidal vascularity index (CVI), presence of cystroid macular edema (CME), macular vessel density (VD) at the superficial and deep capillary plexa, as well as VD of the radial peripapillary capillary (RPC) network, between syndromic and non-syndromic patients with USH2A-associated retinopathy. RESULTS: Thirty-four eyes from 18 patients (7 females) were included. Thirteen patients (72.2%) were affected by Usher syndrome type 2, whereas the remaining 5 subjects (27.8%) had non-syndromic retinitis pigmentosa (nsRP). Syndromic patients were younger than nsRP (p = 0.01) and had a worse visual acuity than those with the exclusively retinal phenotype. Patients with Usher syndrome type 2 had a higher prevalence of CME and a thicker choroid compared to nsRP, although these results were not statistically significant (p = 0.775 and p = 0.122, respectively). Similarly, none of the other quantitative OCT and OCTA parameters was statistically different between the two groups. CONCLUSIONS: Despite their younger age, patients with Usher syndrome type 2 displayed similar choroidal and microvascular changes compared to those with nsRP.

Photoreceptor Integrity in MEWDS: Longitudinal Structure-Function Correlations.

Purpose: The purpose of this study was to investigate structure-function correlations in multiple evanescent white dot syndrome (MEWDS) using microperimetry (MP) and spectral-domain optical coherence tomography (SD-OCT). Methods: Single-center prospective observational study including 14 eyes from 13 patients with MEWDS monitored over a median of 49.5 days (interquartile range = 29-92 days). Investigations focused on best-corrected visual acuity (BCVA), foveal granularity, and the Photoreceptor Reflectivity Ratio (PRR) as a measure of photoreceptor integrity. MP assessed average retinal threshold sensitivity (RTS) and bivariate contour ellipse area (BCEA) for fixation stability. A linear mixed model was used to test associations and interactions among RTS, time, and clinical variables. A hierarchical linear mixed model was used to analyze structure-function relationships, addressing both individual and location-specific variations. Results: Overall, 2340 MP locations were tested. PRR revealed a transient decrease within 30 days post-presentation, indicative of early photoreceptor disruption, followed by a progressive increase, signaling recovery. Significantly lower foveal sensitivity (RTS = 14.8 ± 7.4 vs. 22.5 ± 4.4 decibel [dB], P = 0.04) and increased fixation spread (63% BCEA = 1.26 ± 0.97 vs. 0.48 ± 0.35 deg2, P = 0.06) were noted in eyes with foveal granularity compared to those without. A significant increase in RTS was demonstrated over time (0.066 dB/day, P < 0.001), with a central-to-peripheral gradient of improvement. The interaction between follow-up time and baseline BCVA (P < 0.001) indicated more rapid improvement in eyes with worse initial vision. There was a robust, nonlinear association between PRR and RTS across all tested locations (P < 0.001), becoming asymptotic for sensitivity losses exceeding 20 dB. Conclusions: Photoreceptor reflectivity accurately aligned with visual function in MEWDS on longitudinal examinations. The central-to-peripheral gradient of improvement may suggest specific vulnerabilities underlying the area around the disc.

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.

The Total Macular Burden of Hyperreflective Foci and the Onset of Persistent Choroidal Hypertransmission Defects in Intermediate AMD.

PURPOSE: The association between the total macular burden of hyperreflective foci (HRF) in eyes with intermediate AMD (iAMD) and the onset of persistent choroidal hypertransmission defects (hyperTDs) was studied using swept-source optical coherence tomography (SS-OCT). DESIGN: Post hoc subgroup analysis of a prospective study. METHODS: A retrospective review of iAMD eyes from subjects enrolled in a prospective SS-OCT study was performed. All eyes underwent 6×6 mm SS-OCT angiography (SS-OCTA) imaging at baseline and follow-up visits. En face sub-retinal pigment epithelium (subRPE) slabs with segmentation boundaries positioned 64-400 µm beneath Bruch's membrane (BM) were used to identify persistent choroidal hyperTDs. None of the eyes had persistent hyperTDs at baseline. The same subRPE slab was used to identify choroidal hypotransmission defects (hypoTDs) attributable to HRF located either intraretinally (iHRF) or along the RPE (rpeHRF) based on corresponding B-scans. A semiautomated algorithm was used by two independent graders to validate and refine the HRF outlines. The HRF area and the drusen volume within a 5mm fovea-centered circle were measured at each visit. RESULTS: The median follow-up time for the 171 eyes from 121 patients included in this study was 59.1 months (95%CI: 52.0-67.8 months). Of these, 149 eyes (87%) had HRF, and 82 (48%) developed at least one persistent hyperTD during the follow-up. Although univariable Cox regression analyses showed that both drusen volume and total HRF area were associated with the onset of the first persistent hyperTD, multivariable analysis showed that the area of total HRF was the sole significant predictor for the onset of hyperTDs (P<0.001). ROC analysis identified an HRF area ≥ 0.07 mm² to predict the onset of persistent hyperTDs within one year with an area under the curve (AUC) of 0.661 (0.570-0.753), corresponding to a sensitivity of 55% and a specificity of 74% (P<0.001). CONCLUSIONS: The total macular burden of HRF, which includes both the HRF along the RPE and within the retina, is an important predictor of disease progression from iAMD to the onset of persistent hyperTDs and should serve as a key OCT biomarker to select iAMD patients at high-risk for disease progression in future clinical trials.

Calcified Drusen Prevent the Detection of Underlying Choriocapillaris Using Swept-Source Optical Coherence Tomography Angiography.

Purpose: In age-related macular degeneration (AMD), choriocapillaris flow deficits (CCFDs) under soft drusen can be measured using established compensation strategies. This study investigated whether CCFDs can be quantified under calcified drusen (CaD). Methods: CCFDs were measured in normal eyes (n = 30) and AMD eyes with soft drusen (n = 30) or CaD (n = 30). CCFD density masks were generated to highlight regions with higher CCFDs. Masks were also generated for soft drusen and CaD based on both structural en face OCT images and corresponding B-scans. Dice similarity coefficients were calculated between the CCFD density masks and both the soft drusen and CaD masks. A phantom experiment was conducted to simulate the impact of light scattering that arises from CaD. Results: Area measurements of CCFDs were highly correlated with those of CaD but not soft drusen, suggesting an association between CaD and underlying CCFDs. However, unlike soft drusen, the detected optical coherence tomography (OCT) signals underlying CaD did not arise from the defined CC layer but were artifacts caused by the multiple scattering property of CaD. Phantom experiments showed that the presence of highly scattering material similar to the contents of CaD caused an artifactual scattering tail that falsely generated a signal in the CC structural layer but the underlying flow could not be detected. Similarly, CaD also caused an artifactual scattering tail and prevented the penetration of light into the choroid, resulting in en face hypotransmission defects and an inability to detect blood flow within the choriocapillaris. Upon resolution of the CaD, the CC perfusion became detectable. Conclusions: The high scattering property of CaD leads to a scattering tail under these drusen that gives the illusion of a quantifiable optical coherence tomography angiography signal, but this signal does not contain the angiographic information required to assess CCFDs. For this reason, CCFDs cannot be reliably measured under CaD, and CaD must be identified and excluded from macular CCFD measurements.