Morphology, Fundus Autofluorescence, and Retinal Sensitivity of Photocoagulated Lesions in Proliferative Diabetic Retinopathy.

Purpose: To evaluate the relationships among morphology, fundus autofluorescence (FAF), and retinal sensitivity of photocoagulated lesions more than 1 year after panretinal photocoagulation in patients with proliferative diabetic retinopathy and good vision. Methods: This retrospective cohort study included patients with proliferative diabetic retinopathy who had undergone panretinal photocoagulation more than 1 year ago. The photocoagulated lesions were classified according to FAF levels: group A, no FAF; group B, diffuse FAF; group C, white-dotted centers with diffuse FAF; group D, white-dotted centers without FAF; and group E, controls. The main outcome measures were FAF, retinal sensitivity, and morphology of the photocoagulated lesions. Results: The median sensitivity values and number of photocoagulated lesions in groups A (n = 37), B (n = 39), C (n = 4), D (n = 15), and E (n = 39) were 0 dB, 18.0 dB, 13.9 dB, 0.3 dB, and 21.5 dB, respectively. EZ lines were absent in 93.5%, 18.1%, 50%, 93.3%, and 0% of lesions in groups A, B, C, D, and E, respectively. The inner retinal layer was damaged in 45.2%, 3.0%, 50%, 73.3%, and 0% lesions in groups A, B, C, D, and E, respectively. Statistically significant between-group differences were observed in the retinal sensitivities of the photocoagulated lesions, presence of EZ lines, and damage to the inner retinal layer (p < 0.05). Conclusions: The photoreceptors in most photocoagulated lesions with diffuse FAF retain their morphology and function. Translational Relevance: Using fundus autofluorescence, the damage to photoreceptors after panretinal photocoagulation in patients with diabetes can be estimated in a noninvasive manner. This process can help in determining the need for additional panretinal photocoagulation.

Optical coherence tomography angiography as a potential tool in differential diagnosis of multiple sclerosis and rheumatic disorders with central nervous system involvement.

PURPOSE: The aim of this study is to analyse whether optical coherence tomography angiography (angio-OCT, OCTA) measurements can be a useful tool to differentiate central nervous system (CNS) involvement in rheumatic disorders (RD) from multiple sclerosis (MS). METHODS: A total of 85 patients- 41 with MS, 21 with RD with CNS involvement and 23 healthy controls were included in the study. All individuals underwent OCTA and the following parameters were measured in each eye separately: average foveal and parafoveal vessel density (VD), average foveal and parafoveal vessel length (VL) of the superficial capillary plexus (SCP) and deep capillary plexus (DCP), as well as area, perimeter, and circularity of the foveal avascular zone. RESULTS: OCTA showed a VD reduction in the foveal region of the SCP in eyes of RD patients when compared to MS patients (21.96 ± 3.39 vs.23.88 ± 3.05 (p = 0.003)). There have been no significant differences in any of the assessed parameters that is average VD and total average VL in the foveal area of the SCP as well as of the DCP in the general population comprising healthy controls, MS and RD groups (p > 0.05 for all). CONCLUSIONS: Our results suggest that an OCTA finding of decreased VD in the foveal region of the SCP may be considered as a potentially useful biomarker of RD in comparison with MS patients.

Sema4D Knockout Attenuates Choroidal Neovascularization by Inhibiting M2 Macrophage Polarization Via Regulation of the RhoA/ROCK Pathway.

Purpose: The aim of this study was to elucidate the role of Sema4D in the pathogenesis of senescence-associated choroidal neovascularization (CNV) and to explore its underlying mechanisms. Methods: In this study, we utilized a model of laser-induced CNV in both young (3 months old) and old (18 months old) mice, including those with or without Sema4D knockout. The expression and localization of Sema4D in CNV were assessed using PCR, Western blot, and immunostaining. Subsequently, the morphological and imaging examinations were used to evaluate the size of CNV and vascular leakage. Finally, the expression of M2 markers, senescence-related markers, and molecules involved in the RhoA/ROCK pathway was detected. Results: We found that Sema4D was predominantly expressed in macrophages within CNV lesions, and both the mRNA and protein levels of Sema4D progressively increased following laser photocoagulation, a trend more pronounced in old mice. Moreover, Sema4D knockout markedly inhibited M2 polarization in senescent macrophages and reduced the size and leakage of CNV, particularly in aged mice. Mechanistically, aging was found to upregulate RhoA/ROCK signaling, and knockout of Sema4D effectively suppressed the activation of this pathway, with more significant effects observed in aged mice. Conclusions: Our findings revealed that the deletion of Sema4D markedly inhibited M2 macrophage polarization through the suppression of the RhoA/ROCK pathway, ultimately leading to the attenuation of senescence-associated CNV. These data indicate that targeting Sema4D could offer a promising approach for gene editing therapy in patients with neovascular age-related macular degeneration.

Multimodal Imaging Characteristics and Diagnostic Value of Choroidal Nodules in Patients with Neurofibromatosis Type 1.

Objectives: Yasunari nodules are choroidal lesions observed in patients diagnosed with neurofibromatosis type 1 (NF-1) and characterized by relatively irregular dome-shaped, plaque-like, or patchy boundaries. The present study examines the multimodal imaging characteristics of Yasunari nodules and their value in the diagnosis of NF-1. Materials and Methods: Medical records including optical coherence tomography (OCT), enhanced depth imaging OCT, infrared reflectance (IR) imaging, OCT angiography, and color fundus images of NF-1 patients who were examined at the Department of Ophthalmology in Dokuz Eylül University Faculty of Medicine between January 2022 and December 2023 were retrospectively reviewed for the presence of Yasunari nodules. Results: A total of 54 eyes of 27 patients were included in the study. At least one choroidal nodule was detected on IR imaging in 52 eyes (96.3%). In 31 (72.1%) of the 43 eyes (79.6%) with available high-quality OCT angiography images, choroidal nodules were observed as areas showing a flow deficit in the choriocapillaris layer. Of the total 54 eyes included, Lisch nodules without choroidal nodules were observed in 2 eyes (3.7%). In 16 eyes (29.6%), Lisch nodules were not detected despite the presence of choroidal nodules. Both Lisch nodules and choroidal nodules were detected in the other 36 eyes (66.7%). Conclusion: Yasunari nodules are frequently observed in NF-1 cases and can be easily detected with multimodal imaging techniques, especially IR imaging. The ability to visualize choroidal nodules before the appearance of Lisch nodules demonstrates the importance of Yasunari nodules in the diagnosis of NF-1.

Prognostic factors for intravitreal conbercept in the treatment of choroidal neovascularization secondary to pathological myopia.

PURPOSE: To identify risk factors influencing visual outcomes in patients with pathological myopia-associated choroidal neovascularization (PM-CNV) following intravitreal injections of conbercept. METHODS: A total of 86 eyes from 86 patients received intravitreal conbercept in a 1 + PRN regimen. After the initial injection, patients were followed for 12 months. They were categorized into two groups based on their 12-month visual acuity change: those who achieved greater than a one-line improvement in BCVA (improved group; n = 65) and those who experienced a one-line or lesser improvement or a decrease in BCVA (non-improved group; n = 21). RESULTS: Over the 12-month period, the mean BCVA in the improved group significantly improved from 0.82 to 0.41 LogMAR. In the non-improved group, BCVA changed from 1.24 to 1.09 LogMAR. Similarly, the mean CRT decreased from 426.21 µm at baseline to 251.56 µm at 12 months in the improved group, and from 452.47 to 382.45 µm in the non-improved group. Multivariable logistic regression analyses revealed that older age (OR 1.287; 95% CI 1.019-1.625; P = 0.034), poorer baseline BCVA (OR 6.422; 95% CI 1.625-25.384; P = 0.008), the presence of subfoveal CNV (OR 4.817; 95% CI 1.242-18.681; P = 0.023), and organized interlacing patterns of CNV morphology (OR 5.593; 95% CI 1.397-22.392; P = 0.015) emerged as independent risk factors correlated with worsened visual prognosis following intravitreal conbercept injections. CONCLUSIONS: Conbercept demonstrates significant efficacy and safety in treating PM-CNV. Key factors influencing visual recovery post-treatment include older age, poorer baseline BCVA, the presence of subfoveal CNV, and organized interlacing patterns of CNV morphology.

Visual functions and multimodal imaging of patients with idiopathic focal choroidal excavation.

This study aimed to evaluate visual function and perform multimodal imaging on patients with focal choroidal excavation without any chorioretinal disease (idiopathic focal choroidal excavation [iFCE]). Seventeen eyes of 15 patients with iFCE (8 men, 7 women; mean ± standard deviation age, 56.0 ± 10.8 years) were assessed for visual function including visual acuity, metamorphopsia, aniseikonia, and retinal sensitivity. Multimodal imaging included optical coherence tomography (OCT), fundus autofluorescence (FAF), and OCT angiography. This study found that the maximum width and depth of the excavation were 597 ± 330 (238-1809) µm and 123 ± 45 (66-231) µm, respectively, and that FAF showed normal or hypoautofluorescence corresponding to iFCE. The fundus examination findings were stable during the follow-up period (96 ± 48 months). None of the eyes showed any abnormalities in central retinal sensitivity or aniseikonia. Metamorphopsia was detected using Amsler grid testing and M-CHARTS in two eyes. Therefore, this study is the first to quantitatively and qualitatively study metamorphopsia of patients with iFCE. Our results showed that most patients with iFCE did not have visual impairments, despite the presence of morphological changes in the outer retina and choroid.

Associations of retinal microvascular alterations with diabetes mellitus: an OCTA-based cross-sectional study.

BACKGROUND: Diabetes, a health crisis afflicting millions worldwide, is increasing rapidly in prevalence. The microvascular complications triggered by diabetes have emerged as the principal cause of renal disease and blindness. The retinal microvascular network may be sensitive to early systemic vascular structural and functional changes. Therefore, this research endeavored to discern the systemic determinants influencing the retinal microvascular network in patients with and without diabetes. METHODS: The Kailuan Eye Study is a cross-sectional study based on the community-based cohort Kailuan Study. Participants underwent optical coherence tomography angiography (OCTA) (Zeiss Cirrus 5000; Carl Zeiss Meditec) and comprehensive systemic examination. Metrics such as perfusion density (PD), vascular density (VD), foveal avascular zone (FAZ) parameters of the superficial capillary plexus (SCP) in the macula were assessed. RESULTS: This study included 860 eligible participants (average age = 62.75 ± 6.52 years; 21.9% female), of which 449 were diabetics. People with diabetes had diminished PD and VD in the entire macular and parafoveal regions compared to people without diabetes. Reduced PD in the whole macular region was correlated with higher fasting plasma glucose (FPG, mmol/L) concentration (Beta = -0.19, 95% CI = -0.42 to -0.36, P < 0.001), longer axial length (AL, mm) (Beta = -0.13, 95%CI = -0.48 to -0.25, P = 0.002), and elevated heart rate (Beta = -0.10, 95%CI = -0.14 to -0.19, P = 0.014), after adjusting for younger age (Beta = -0.18, 95%CI = -0.24 to -0.35, P < 0.001), consistent with VD of the whole macular region. A higher FPG level was significantly correlated with lower SCP density of both PD and VD in the macular and parafoveal region (P < 0.05 for all), as well as increased systolic blood pressure and low-density lipoprotein cholesterol concentration (P < 0.01 for all). CONCLUSIONS: In this large-sample cross-sectional study, OCTA evaluation revealed that high prevalence of diabetes and elevated FPG levels were correlated with reduced retinal VD and PD. Hypertension and hyperlipidemia are important risk factors for the development of atherosclerotic cardiovascular disease but have no significant effect on retinal microvascular abnormalities.

Multiple evanescent white dot syndrome associated with COVID-19 infection: a case report.

BACKGROUND: To report a case of Multiple Evanescent White Dot Syndrome (MEWDS) one month after a COVID-19 infection in a female patient at an age unusual for the occurrence of this disease. CASE PRESENTATION: A 69-year-old Caucasian female reported the presence of floaters, photopsia, and enlarging vision loss in her left eye following the COVID-19 infection. Clinical and multimodal imaging was consistent with the MEWDS diagnosis. Fluorescein angiography examination revealed characteristic hyperfluorescent spots around the fovea in a wreath-like pattern. An extensive lab workup to rule out other autoimmune and infectious etiologies was inconclusive. Visual acuity and white dots resolved after a course of corticosteroids, which was confirmed on follow-up dilated fundus exam and multimodal imaging. CONCLUSIONS: MEWDS is a rare white dot syndrome that may occur following COVID-19 infection in addition to other reported ophthalmic disorders following this infection.

Investigation of factors that may affect the foveal avascular zone: An optical coherence tomography angiography study.

SIGNIFICANCE: An understanding of factors that affect the foveal avascular zone (FAZ) in healthy eyes may aid in the early identification of patients at risk of retinal pathology, thereby allowing better management and preventive measures to be implemented. PURPOSE: The size and shape of the FAZ can change due to retinal diseases associated with oxidative stress, including diabetic retinopathy, glaucoma, and macular degeneration. This study aimed to assess the relationship, if any, between factors that may affect the superficial FAZ (i.e., vessel density, vessel perfusion, overweight/obesity) and possible links with macular pigment optical density in young, healthy participants. METHODS: One hundred thirty-nine participants aged 18 to 35 years were recruited to this cross-sectional study. The superficial FAZ area, foveal vascularity, and central macular thickness (CMT) were assessed using the Cirrus 5000. Health parameters, body mass index, trunk fat %, and macular pigment were analyzed to determine possible associations with the superficial FAZ. RESULTS: Mean FAZ area was 0.23 ± 0.08 mm2. Females had a significantly larger mean FAZ area than males (p=0.002). The FAZ area was positively correlated with body mass index (Pearson's r = 0.189, p=0.026). Significant correlates of the FAZ area in the multivariate model included vessel perfusion (central), CMT, and trunk fat %, collectively explaining 65.1% of the overall variability. CONCLUSIONS: Study findings suggest that reduced vessel perfusion, thinner CMT, and higher trunk fat % are plausible predictors of a larger FAZ area in healthy Caucasian adults. Low macular pigment optical density was, however, not associated with increased FAZ size in young healthy eyes. Noninvasive optical coherence tomography angiography testing, in association with these predictors, may aid in the early detection and monitoring of retinal diseases associated with oxidative stress.

Intereye Microvascular Differences in Patients With Same-Stage Diabetic Retinopathy Revealed by OCTA.

Purpose: To evaluate microvascular intereye differences in diabetic patients with same-stage diabetic retinopathy (DR) in both eyes as assessed using optical coherence tomography angiography (OCTA). Methods: In this cross-sectional study, fovea-centered swept-source 6 × 6 mm OCTA scans were acquired using a 200 kHz OCTA device. Vessel density (VD) and fractal dimension were calculated on binarized, vessel-segmented images in the superficial capillary plexus (SCP) and deep capillary plexus (DCP). Foveal avascular zone (FAZ) area (FAZA) and perimeter (FAZP) was measured and FAZ circularity (FAZC) calculated. Absolute difference (δabs) and asymmetry index between eyes was assessed and compared across DR stages. Differences of VD, FD, and FAZ parameters between left and right eye were evaluated using linear mixed models. Results: A total of 336 eyes of 168 diabetic patients without DR and with DR stages ranging from mild nonproliferative to proliferative DR were included for analysis. The intereye comparison revealed significantly lower VD in the SCP (estimate [95% CI] = -0.009 [-0.01; -0.006], P < 0.01), as well as a significantly lower FD in the SCP (-0.007 [-0.009; -0.005], P < 0.01) of the left compared to the right eye. FAZC of the left compared to the right eye was lower in eyes without DR, moderate DR, and PDR (P < 0.05). FAZ δabs and asymmetry index were higher in more advanced disease stages (P < 0.05). Conclusions: OCTA metrics provide important information on the retinal microvasculature in systemic diseases such as DR. Our results reveal a significant intereye difference with lower VD and FD in the SCP as well as higher FAZ impairment of the left compared to the right eye.

Swept-source optical coherence tomography and swept-source optical coherence tomography angiography findings in circumscribed choroidal hemangioma before and after transpupillary thermotherapy.

PURPOSE: To investigate the swept-source optical coherence tomography (SS-OCT) and SS-OCT angiography (SS-OCTA) findings in circumscribed choroidal hemangioma (CCH) before and after treatment with transpupillary thermotherapy (TTT). METHODS: The clinical records of 21 eyes having CCH imaged with SS-OCT/SS-OCTA between September 2018 and December 2022 were evaluated. RESULTS: SS-OCT examination in CCH showed dome-shaped appearance (100%), choroidal shadowing (100%), expansion of choroidal structures (100%), subretinal fluid (66.7%), intraretinal edema/schisis (33.3%), retinal pigment epithelium (RPE) atrophy (19.0%), hyperreflective dots (19.0%), and epiretinal membrane (4.8%). Internal arborizing tumor vessels showing hyperreflectivity were observed in the choriocapillaris slab on SS-OCTA in all eyes. In the deep capillary plexus (DCP), flow void changes were seen in 7 eyes with intraretinal schisis/cystoid macular edema. Four CCHs > 2 mm in thickness showed outer retinal involvement due to unmasking of flow in intratumoral vessels related to RPE atrophy. Following TTT/indocyanine green-enhanced TTT (ICG-TTT) of CCH, SS-OCT findings included total/partial resolution of subretinal fluid (57.1%), complete/partial regression of the tumor (52.4%), and RPE atrophy (33.3%). After treatment; loss of choriocapillaris, decrease in tumor vascularity together with increase in the fibrous component and flow void areas were detected on SS-OCTA. CONCLUSIONS: SS-OCT/SS-OCTA are useful non-invasive tools for imaging the structural/vascular changes in CCHs managed with TTT or ICG-TTT. On SS-OCTA, hyporeflective spaces localizing to edema/schisis in the DCP and arborizing tumor vessels within a hyporeflective stromal background in the choriocapillaris slab were observed. After TTT/ICG-TTT, a decrease in tumor vessels and an increase in the fibrous component and flow-void areas inside the CCH were detected on SS-OCTA.

FROM OUTER RETINAL NEOVACULARIZATION TO EXUDATIVE SUBRETINAL NEOVASCULARIZATION IN MACULAR TELANGIECTASIA TYPE 2.

PURPOSE: To describe the progression from outer retinal neovascularization (ORNV) to exudative subretinal new vessels (SRNVs) in idiopathic macular telangiectasia type 2. METHODS: A total of 135 patients (270 eyes) imaged with optical coherence tomography angiography were included. MAIN OUTCOME MEASURES: Ellipsoid zone loss, outer retinal hyperreflectivity, ORNV, and SRNVs. Outer retinal neovascularization was defined as a flow signal passing through the outer plexiform layer, with or without vertical linear outer retinal hyperreflectivity on the optical coherence tomography B-scan. Subretinal new vessels were defined as an abnormal capillary network with a peripheral anastomotic arcade seen on en face optical coherence tomography angiography and a convex hyperreflectivity at the retinal pigment epithelium. RESULTS: Subretinal new vessels were observed in 38/270 eyes (14%). Subretinal new vessels were at a fibrotic stage in 24/38 eyes and at an exudative stage in 6/38 eyes, and a progression from ORNV to SRNVs was documented in 8/38 eyes. All cases showed an ellipsoid zone loss. In seven eyes (2.5%), SRNVs were also associated with subepithelial neovascularization. No retinochoroidal anastomosis was detected. The visual acuity dropped when SRNVs were present. CONCLUSION: In this case series, SRNVs were found in 14% of eyes. In all cases, they were associated with an ellipsoid zone loss and with outer retinal hyperreflectivity. A progression from ORNV to SRNVs was observed.

Update on central retinal artery occlusion.

The medical condition referred to as "central retinal artery occlusion" (CRAO) was first documented by Albrecht von Graefe in 1859. Subsequently, CRAO has consistently been identified as a serious medical condition that leads to substantial visual impairment. Furthermore, it is correlated with vascular complications that have the potential to affect crucial organs such as the brain and heart. A considerable amount of research has been extensively published on the various aspects of this topic, which is marked by notable debates and misconceptions, especially regarding its management and outcomes. The primary aim of this review article is to analyze the latest developments in the understanding of CRAO, which includes its causes, techniques for retinal imaging, systemic evaluation, and therapeutic strategies, such as vitrectomy. This review article offers readers a comprehensive learning experience to gain knowledge on the fundamental principles and recent advancements in CRAO.

Predictive factors of age-related macular degeneration with poor response to three loading doses of anti-vascular endothelial growth factor.

PURPOSE: To evaluate the predictive factors of neovascular age-related macular degeneration (nAMD) with poor response to three loading doses of intravitreal bevacizumab (IVB). METHODS: A retrospective cohort study was performed on nAMD patients three loading IVB initial treatment. The patients were divided into two groups, without residual fluid on optical coherence tomography (OCT) images (Group 1) and with residual fluid (Group 2). Demographic data, OCT findings, and morphological features of macular neovascularization (MNV) in optical coherence tomography angiography (OCTA) were recorded. RESULTS: The study included one hundred thirty-six eyes of 120 patients (Group 1: n = 66 eyes, Group 2: n = 70 eyes). Central macular thickness, presence of intraretinal fluid, subretinal fluid, hyperreflective foci-band, pigment epithelial detachment (PED), and prechoroidal cleft were similar between the two groups. Pre-injection central choroidal thickness (CCT) was 214.17 ± 50.28 µm in Group 1 and 247.40 ± 60.55 µm in Group 2 (p = 0.021). PED width (p = 0.028) and PED area (p = 0.042) were statistically significantly higher in Group 1. When the morphology of MNV in OCTA was examined, branching (p = 0.736), loops (p = 0.442), peripheral arcade (p = 0.600), hypointense halo (p = 0.779), sea fan (p = 0.250), medusa (p = 0.255), pruned vascular tree pattern (p = 0.148), capillary fringe (p = 0.683) were similar in both groups. The presence of a closed circuit pattern was significantly higher in Group 2 (p = 0.028). CONCLUSION: Initial CCT and closed circuit pattern MNV were higher in IVB-resistant cases. It was observed that PEDs with large bases and areas responded significantly better to loading therapy. The presence of a closed-circuit pattern was an independent risk factor for poor response to loading therapy. Retrospectively registered. REGISTRATION NUMBER: 2011-KAEK-25 2023/05-08.

Efficacy of anti-VEGF intravitreal injection in traumatic submacular hemorrhage: a retrospective study.

OBJECTIVE: In this study we investigated the efficacy of short-term intravitreal injections of anti-vascular endothelial growth factors (anti-VEGF) in treating traumatic submacular hemorrhage. METHODS: A total of 115 patients were diagnosed with submacular hemorrhage between 2018 and 2022 at Shenzhen Eye Hospital. In a retrospective analysis, we examined 13 of these patients who presented with submacular hemorrhage and choroidal rupture due to ocular trauma. Eight patients were treated with intravitreal anti-VEGF injection and 5 with oral drugs. We systematically analyzed changes in their ocular conditions pre and post-treatment. The evaluations encompassed best-corrected visual acuity (BCVA), optical coherence tomography, fundus fluorescein angiography, and retinal imaging. RESULTS: The 13 patients diagnosed with submacular hemorrhage comprised of 10 males and 3 female, with their age ranging between 27 and 64 years, with an average age of 38.1 years (standard deviation [SD]: 11.27). A statistically significant reduction in central foveal thickness (CFT) was observed following intravitreal injections of anti-VEGF drugs (P = 0.03). In control group, the CFT was reduced without statistical significance (P = 0.10). The BCVA of the patients in treatment group improved significantly from 1.15 (SD: 0.62. Range: 0.4-2) to 0.63 (SD: 0.59. Range: 0.1-1.6), indicating an average increase of 4.13 lines (SD: 3.36. Range: 0-9) as measured by the visual acuity test using an eye chart (P = 0.01). The difference between baseline visual acuity and final visual acuity was not statistically significant in control group (P = 0.51). CONCLUSION: Short-term administration of anti-VEGF drugs exhibited significant efficacy in reducing submacular hemorrhage following ocular trauma and enhancing visual acuity.

Multicentric Longitudinal Prospective Study in a European Cohort of MYO7A Patients: Disease Course and Implications for Gene Therapy.

Purpose: We investigated the natural history of retinal dystrophy owing to variants in the MYO7A gene. Methods: Fifty-three patients (mean age, 33.6 ± 16.7 years) with Usher syndrome owing to biallelic, mostly pathogenic, variants in MYO7A underwent baseline and two annual follow-up visits. Best-corrected visual acuity (BCVA), semiautomatic kinetic visual field, full-field electroretinogram, color fundus imaging, microperimetry, spectral-domain optical coherence tomography, and fundus autofluorescence were assessed. Results: At baseline, all patients presented with decreased BCVA (66.4 ± 17.9 Early Treatment Diabetic Retinopathy score and 59.5 ± 21.7 Early Treatment Diabetic Retinopathy score, in the better- and worse-seeing eyes, respectively), restricted semiautomatic kinetic visual field (III4e area, 3365.8 ± 4142.1°2; 4176.4 ± 4400.3°2) and decreased macular sensitivity (9.7 ± 9.9 dB; 9.0 ± 10.2 dB). Spectral-domain optical coherence tomography revealed reduced central macular thickness (259.6 ± 63.0 µm; 250.7 ± 63.3 µm) and narrowed ellipsoid zone band width (2807.5 ± 2374.6 µm; 2615.5 ± 2370.4 µm). Longitudinal analyses (50 patients) showed a significant decrease of BCVA in better-seeing eyes, whereas no changes were observed in worse-seeing eyes for any parameter. BCVA, semiautomatic kinetic visual field (III4e and V4e) and macular sensitivity were related significantly to age at baseline. Hyperautofluorescent foveal patch (16 eyes [31.4%]) and abnormal central hypoautofluorescence (9 eyes [17.6%]) were significantly associated with worse morphological and functional read-outs compared with the hyperautofluorescent ring pattern (22 eyes [43.1%]). Conclusions: Our European multicentric study offers the first prospective longitudinal analysis in one of the largest cohorts of MYO7A patients described to date, confirming the slow disease progression. More important, this study emphasizes the key role of fundus autofluorescence patterns in retinal impairment staging and advocates its adoption as an objective biomarker in patient selection for future gene therapy 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.