Small Hyperreflective Retinal Foci as in vivo imaging feature of resident microglia activation in geographic atrophy.

Geographic atrophy (GA), the atrophic late stage of age-related macular degeneration (AMD), is one of the leading causes of vision loss in developed countries. Based on genetic, histological and preclinical studies, the role of the innate immune system in the development and progression of GA is well established. Microglia, the principal resident immune cells, are recognized as key players in innate immunity and contributors to AMD development. Optical coherence tomography (OCT) allows to identify small hyperreflective retinal foci (HRF) with specific features known as aggregates of activated microglial cells as possible in vivo imaging feature of local neuroretinal inflammation. The purpose of this study was to evaluate the presence and amount of small HRF in the eyes of patients with different macular atrophic phenotypes. Patients with GA in both eyes (bilateral GA: B-GA group), patients with GA in one eye and macular new vessels (MNV) in the fellow-eye (unilateral GA: U-GA group) and patients with extensive macular atrophy with pseudodrusen (EMAP), a rare and aggressive variant of atrophic AMD, were retrospectively analyzed. HRF, defined as isolated punctiform elements of small dimensions (≤30 µm) with intermediate reflectivity (similar to that of the nerve fiber layer) and without a shadow cone, were manually identified and quantified. The amount of HRF was correlated to best corrected visual acuity (BCVA), GA lesion size, measured both at near infrared reflectance (NIR), and blue wavelength fundus autofluorescence (FAF) images, to some GA features (multifocal versus unifocal GA; presence versus absence of foveal sparing) and to central retinal thickness (CRT). Forty-six patients (26 in the B-GA group, 16 in the U-GA group and 4 in the EMAP group) were studied. Patients with EMAP were younger compared to patients with B-GA and to patients with U-GA (63.5 ± 6.8 years vs 80.4 ± 8.4 years B-GA, and vs 83.3 ± 6.1 years U-GA; p = 0.0004 and p= <0.0001, respectively). Mean BCVA, mean GA area at NIR and at FAF images, foveal sparing and multifocal versus unifocal GA distribution and mean CRT were not significantly different among groups. GA area was wider on NIR versus FAF in all groups, significantly in B-GA and U-GA groups (11.7 ± 7.6 mm2 vs 10.6 ± 7.1 mm2, p = 0.0087 in B-GA; 7.8 ± 9.2 mm2 vs 7.7 ± 9.4 mm2, p = 0.004 in U-GA). The number of HRF was significantly higher in U-GA compared to B-GA and to EMAP (47.4 ± 7.1 vs 31.6 ± 7.3 B-GA and 28.0 ± 4.9 EMAP, p < 0.0001 for both), while mean HRF number did not significantly differ between B-GA and EMAP (p = 0.1960). HRF count correlated only to CRT, positively in B-GA and negatively in U-GA group. The increase of small HRF, which mirrors retinal microglial activation, characterizes eyes with unilateral GA (and MNV in the fellow eye) but not eyes with bilateral GA or EMAP. The role of activated microglia in the retina of GA eyes needs to be better investigated, mainly considering the actual and new therapeutic strategies with which to reduce either the development or progression of the atrophic macular changes.

Hyperreflective choroidal foci in diabetic eyes with and without macular edema: Novel insights on diabetic choroidopathy.

Histopathologic studies of diabetic choroid suggest that diabetic choroidopathy is a key aspect secondary to diabetes. Recently, hyperreflective choroidal foci (HCF) have been introduced as novel optical coherence tomography (OCT) parameter. The aim of this study was to identify and quantify HCF in diabetic subjects with retinopathy, with or without diabetic macular edema (DME). Eighty-five diabetic subjects with different degrees of DR were enrolled: 37 without DME and 48 with DME. All subjects underwent full ophthalmologic examination including spectral domain optical coherence tomography (OCT). OCT images were analyzed to quantify and localize HCF. Each image was analyzed by two independent, masked examiners. OCT images showed that all subjects (100%) had HCF in the different layers of the choroid. The number of HCF was significantly higher in diabetics with DME versus those without DME (p < 0.0001). HCF showed variable size, shape and location inside the choroid. They were mainly located in choriocapillaris and Sattler's layer, on the edges of blood vessels. The intraobserver and interobserver agreement was almost perfect (ICC >0.9). This study suggests that hyperreflective foci in the choroid of subjects with DR may be accurately identified with structural OCT. Their number significantly increases with the progression of DME. These HCF may represent, as in the retina, a sign of infiltration of inflammatory cells (mainly migrating microglia) into the choroid, according to the hypothesis raised by Jerry Lutty. HCF may confirm in vivo the histopathologic findings suggesting that diabetic choroidopathy may be primarily a neuroinflammatory disorder.

Role of inflammation in diabetic macular edema and neovascular age-related macular degeneration.

Diabetic macular edema (DME) and neovascular age-related macular degeneration (nAMD) are multifactorial disorders that affect the macula and cause significant vision loss. Although inflammation and neoangiogenesis are hallmarks of DME and nAMD, respectively, they share some biochemical mediators. While inflammation is a trigger for the processes that lead to the development of DME, in nAMD inflammation seems to be the consequence of retinal pigment epithelium and Bruch membrane alterations. These pathophysiologic differences may be the key issue that justifies the difference in treatment strategies. Vascular endothelial growth factor inhibitors have changed the treatment of both diseases, however, many patients with DME fail to achieve the established therapeutic goals. From a clinical perspective, targeting inflammatory pathways with intravitreal corticosteroids has been proven to be effective in patients with DME. On the contrary, the clinical relevance of addressing inflammation in patients with nAMD has not been proven yet. We explore the role and implication of inflammation in the development of nAMD and DME and its therapeutical relevance.

Hyper-reflective foci changes in RRMS under natalizumab therapy.

Introduction: Microglia (MG) is suggested to play an immunopathological role of in Multiple Sclerosis (MS). Since hyper-reflective foci (HRF) might mark MG activation, in vivo analysis by Optic Coherence Tomography (OCT) in MS patients under disease modifying therapies may help to clarify MS immunopathology as well as drug's mechanism of intrathecal action. Objective: To analyze HRF in patients treated with Natalizumab (NTZ), a high efficacy therapy for MS. Materials and methods: The effect of NTZ on the retina of 36 Relapsing-Remitting MS patients was investigated in a prospective, single-center study. OCT was performed immediately before the first infusion and then between infusion 3 and 4, infusion 6 and 7, infusion 11 and 13. Peripapillary and macular scans were acquired, evaluating peripapillary RNFL thickness, macular volumes (vertical scans), and HRF count (horizontal scan) in Ganglion Cell Layer (GCL), Inner Plexiform Layer (IPL) and Inner Nuclear Layer (INL). Clinical examination was performed every six months. Results: HRF count significantly increased under NTZ therapy (p<0.001) in both GCL (18.85 ± 6.93 at baseline, 28.24 ± 9.55 after 12 months) and IPL (25.73 ± 7.03 at baseline, 33.21 ± 8.50 after 12 months) but remained stable in INL (33.65 ± 7.76 at baseline, 36.06 ± 6.86 after 12 months, p=0.87), while no relevant modification of pRNFL and macular volumes were observed during the study. EDSS remained stable and no clinical relapse was observed between month 6 and 12. Conclusion: In RRMS NTZ affects HRF count in GCL and IPL, but not in INL, suggesting that NTZ does not impact on some aspects of MS immunopathology.

The Disorganization of Retinal Inner Layers Is Correlated to Müller Cells Impairment in Diabetic Macular Edema: An Imaging and Omics Study.

The disorganization of retinal inner layers (DRIL) is an optical coherence tomography (OCT) biomarker strictly associated with visual outcomes in patients with diabetic macular edema (DME) whose pathophysiology is still unclear. The aim of this study was to characterize in vivo, using retinal imaging and liquid biopsy, DRIL in eyes with DME. This was an observational cross-sectional study. Patients affected by center-involved DME were enrolled. All patients underwent spectral domain optical coherence tomography (SD-OCT) and proteomic analysis of aqueous humor (AH). The presence of DRIL at OCT was analyzed by two masked retinal experts. Fifty-seven biochemical biomarkers were analyzed from AH samples. Nineteen eyes of nineteen DME patients were enrolled. DRIL was present in 10 patients (52.63%). No statistically significant difference was found between DME eyes with and without DRIL, considering the AH concentration of all the analyzed biomarkers except for glial fibrillary acidic protein (GFAP), a biomarker of Müller cells dysfunction (p = 0.02). In conclusion, DRIL, in DME eyes, seems to strictly depend on a major dysfunction of Müller cells, explaining its role not only as imaging biomarker, but also as visual function Müller cells-related parameter.

Validation of an Automated Artificial Intelligence Algorithm for the Quantification of Major OCT Parameters in Diabetic Macular Edema.

Artificial intelligence (AI) and deep learning (DL)-based systems have gained wide interest in macular disorders, including diabetic macular edema (DME). This paper aims to validate an AI algorithm for identifying and quantifying different major optical coherence tomography (OCT) biomarkers in DME eyes by comparing the algorithm to human expert manual examination. Intraretinal (IRF) and subretinal fluid (SRF) detection and volumes, external limiting-membrane (ELM) and ellipsoid zone (EZ) integrity, and hyperreflective retina foci (HRF) quantification were analyzed. Three-hundred three DME eyes were included. The mean central subfield thickness was 386.5 ± 130.2 µm. IRF was present in all eyes and confirmed by AI software. The agreement (kappa value) (95% confidence interval) for SRF presence and ELM and EZ interruption were 0.831 (0.738-0.924), 0.934 (0.886-0.982), and 0.936 (0.894-0.977), respectively. The accuracy of the automatic quantification of IRF, SRF, ELM, and EZ ranged between 94.7% and 95.7%, while accuracy of quality parameters ranged between 99.0% (OCT layer segmentation) and 100.0% (fovea centering). The Intraclass Correlation Coefficient between clinical and automated HRF count was excellent (0.97). This AI algorithm provides a reliable and reproducible assessment of the most relevant OCT biomarkers in DME. It may allow clinicians to routinely identify and quantify these parameters, offering an objective way of diagnosing and following DME eyes.

Current Management of Patients with RPE65 Mutation Associated Inherited Retinal Degenerations in Europe: Results of a 2-Year Follow-Up Multinational Survey.

INTRODUCTION: The aim of this study was to evaluate the current management of RPE65 biallelic mutation-associated inherited retinal degeneration (RPE65-IRD) in Europe since market authorization of voretigene neparvovec (VN, LuxturnaTM) in 2018. By July 2022, over 200 patients have been treated outside the USA, of whom about 90% in Europe. We conducted among all centers of the European Vision Institute Clinical Research Network (EVICR.net) and health care providers (HCPs) of the European Reference Network dedicated to Rare Eye Diseases (ERN-EYE) the second multinational survey on management of IRDs in Europe elaborated by EVICR.net with a special focus on RPE65-IRD. METHODS: An electronic survey questionnaire with 48 questions specifically addressing RPE65-IRD (2019 survey 35) was developed and sent by June 2021 to 95 EVICR.net centers and 40 ERN-EYE HCPs and affiliated members. Of note, 11 centers are members of both networks. Statistical analysis was performed with Excel and R. RESULTS: The overall response rate was 44% (55/124); 26 centers follow RPE65 biallelic mutation-associated IRD patients. By June 2021, 8/26 centers have treated 57 RPE65-IRD cases (1-19/center, median 6) and 43 planned for treatment (range 0-10/center, median 6). The overall age range was 3-52 years, and on average 22% of the patients did not (yet) qualify for treatment (range 2-60%/center, median 15%). Main reasons were too advanced (range 0-100, median 75%) or mild disease (range 0-100, median 0). Eighty-three percent of centers (10/12) that follow RPE65 mutation-associated IRD patients treated with VN participate in the PERCEIVE registry (EUPAS31153, http://www.encepp.eu/encepp/viewResource.htm?id=37005). Quality of life and full-field stimulus test improvements had the highest scores of the survey-reported outcome parameters in VN treatment follow-up. CONCLUSION: This second multinational survey on management of RPE65-IRD by EVICR.net centers and ERN-EYE HCPs in Europe indicates that RPE65-IRD might be diagnosed more reliably in 2021 compared to 2019. By June 2021, 8/26 centers reported detailed results including VN treatment. Main reasons for non-treatment were too advanced or mild disease, followed by absence of 2 class 4 or 5 mutations on both alleles or because of a too young age. Patient satisfaction with treatment was estimated to be high by 50% of the centers.

Current Management of Inherited Retinal Degeneration Patients in Europe: Results of a 2-Year Follow-Up Multinational Survey by the European Vision Institute Clinical Research Network - EVICR.net.

INTRODUCTION: An increasing number of gene-specific therapies are being developed for inherited retinal degenerations (IRDs). Identification of well-characterized patients is an emerging need. We conducted the second multinational survey among the EVICR.net and ERN-EYE members to understand the management and treatment of IRDs in Europe and compared it to the 2019 survey. METHODS: An electronic survey questionnaire was developed and sent to 124 clinical centers (25 countries) by June/July 2021. Statistical analysis was performed with Excel and R. RESULTS: The overall response rate was 44% but varied among countries. Only 9% of responding centers do not see IRD patients (2019 survey 14%), 42% follow at least 200 patients per year, 18% follow 500-999, and 2% more than 1,000. Databases exist in 86% of the centers (local 86%; national web based 12%). IRD patients are referred to EVICR.net and ERN-EYE centers mainly by general ophthalmologists, patient self-referral, or medical retina specialists. Most IRD patients are first seen as adults. Signs and symptoms depend on age of onset: in infancy, nystagmus; at older age, night blindness and reduced visual field; reduced visual acuity is described at any age. Comprehensive ophthalmic examination always includes visual acuity and almost always visual field multimodal retinal imaging, electrophysiology, color vision testing, and refraction. Identification of genotypes is successful in 72% of centers in 40-80% of cases (2019 survey 69% of centers). The time for confirmation of the genetic diagnosis varies from 2-4 weeks to 24 months (2019 survey >4 weeks ≤10 years). Genetic testing is covered by public health service in 83%, private health insurance in 29%, research funds in 24%; 5% do not have access to genetic testing (2019 survey 15%). The most striking result is the high increase in the involvement of centers in natural history and gene therapy trials that more than doubled for the latter. DISCUSSION: This second multinational survey on management of IRDs in Europe highlights persistent important differences in the number of IRD patients managed per center, comparable diagnostic work-up, and increasing genotyping in diagnostic laboratories. The important increase in involvement of centers in natural history and gene therapy trials reflects the rapidly evolving field of gene therapy development. The survey provides important follow-up data for researchers, clinicians, caregivers, patient advocate groups, pharmaceutical companies, and investors.

Proptosis secondary to bilateral extraocular muscle enlargement in Noonan syndrome with hypertrophic cardiomyopathy: A case report.

PURPOSE: To report and investigate proptosis in a young girl with Noonan syndrome. METHODS: Observational case report. RESULTS: A 16-year-old girl affected by Noonan syndrome underwent a complete ophthalmological examination showing bilateral proptosis with hypofunction of lateral rectus and superior oblique muscles. Visual acuity, color discrimination and fundus examination were unremarkable. The orbital MRI showed bilateral proptosis and symmetrical enlargement of extraocular muscles, with bellies thickening and tendon sparing. The young patient also complained restrictive hypertrophic cardiomyopathy. CONCLUSIONS: Proptosis is an uncommon ocular manifestation of Noonan syndrome and its pathophysiology has never been clarified. The MRI evidence of extraocular muscles enlargement associated with hypertrophic cardiomyopathy, led us to hypothesize a common altered pathway beneath these features, more specifically the MAP kinase pathway, since extraocular and cardiac muscles share a mesenchymal embryological origin.

Outer Retinal and Choroidal Changes in Adolescents with Long-Lasting Type 1 Diabetes.

This study aimed to assess outer retinal layer (ORL), retinal pigment epithelium (RPE), choroid (Ch) and choriocapillaris (CC) modifications in adolescents with long-lasting (>10 years) type 1 diabetes (T1D) without (noDR) or with diabetic retinopathy (DR). ORL and RPE thickness were measured at optical coherence tomography (OCT) macular scans. Vascular parameters of Ch and CC were quantified after elaboration of macular OCT-angiography (OCTA) images. Insulin dose and auxological and metabolic parameters were correlated with OCT and OCTA findings in patients. ORL thickness was higher in DR eyes than in noDR and healthy controls (HC), and RPE thickness was higher in noDR and DR eyes than in HC, with statistical significance for some sectors in noDR versus HC. No OCTA parameters of CC and Ch differed among groups, and no significant correlation was observed with auxological and metabolic parameters. In conclusion, ORL and RPE were both increased in adolescents with long-lasting T1D. Such changes were not associated with insulin dose and glycemia control, nor to any choroid or choriocapillaris flow change clinically detectable at OCTA, and they could be potential imaging biomarkers of disease progression.

Hyper-reflective retinal foci as possible in vivo imaging biomarker of microglia activation in von Hippel-Lindau disease.

PURPOSE: von Hippel-Lindau (VHL) disease is caused by a mutation of the VHL gene and characterized by the development of retinal hemangioblastomas (RH). Current pathophysiologic mechanisms of RH development and progression are still insufficient to predict RH behavior. VHL gene is involved in the cellular response to hypoxia and in many intracellular signaling pathways expressed both in angiogenesis and inflammation. Optical coherence tomography (OCT) allows to identify hyper-reflective retinal foci (HRF) known as aggregates of activated microglial cells as possible in vivo biomarker of local inflammation. The aim of the present study was to investigate the presence of HRF in patients with genetically confirmed VHL disease. METHODS: In this cross-sectional study, patients with VHL underwent complete ophthalmological examination and OCT with HRA + OCT Spectralis. HRF were manually identified and calculated in inner (IR), outer (OR) and full retina. Age-matched healthy subjects were enrolled as controls. RESULTS: 113 eyes of 63 VHL patients and 56 eyes of 28 healthy subjects were evaluated. HRF number was significantly higher in VHL than in controls in IR (28.06 ± 7.50 vs 25.25 ± 6.64, p = 0.042). No difference was observed in OR and in full retina (OR: 7.73 ± 2.59 vs 7.95 ± 2.51, p = 0.599; full retina: 35.79 ± 8.77 vs 33.20 ± 7.47, p = 0.093). CONCLUSION: The increase of HRF, which mirror retinal microglial activation, characterizes VHL eyes. The role of activated microglia in the retina of VHL eyes needs to be better investigated, mainly considering local VHL disease manifestations.

The Narrative Medicine Approach in the Treatment of Diabetic Macular Edema: An Italian Experience.

The study retraces the healthcare pathway of patients affected by diabetic macular edema (DME) through the direct voice of patients and caregivers by using a "patient journey" and narrative method approach. The mapping of the patient's journey was developed by a multidisciplinary board of health professionals and involved four Italian retina centers. DME patients on intravitreal injection therapy and caregivers were interviewed according to the narrative medicine approach. Narratives were analyzed through a quali-quantitative tool, as set by the narrative medicine method. The study involved four specialized retina centers in Italy and collected a total of 106 narratives, 82 from DME patients and 24 from caregivers. The narratives reported their difficulty in identifying the correct pathway of care because of a limited awareness of diabetes and its complications. Patients experienced reduced autonomy due to ocular complications. In the treatment of diabetes and its complications, a multidisciplinary approach currently appears to be missing. DME reduces the quality of life of affected patients. The narrative medicine approach offers qualitative and emotional patient-guided information. The patient journey provides all of those involved in the management of DME with flowcharts to refer to, identifying the critical points in the healthcare journey of DME patients to improve the management of the disease.

Retinal Microvascular and Neuronal Changes Are Also Present, Even If Differently, in Adolescents with Type 1 Diabetes without Clinical Diabetic Retinopathy.

The purpose of this study was to evaluate retinal changes in adolescents with childhood-onset, long-lasting type 1 diabetes mellitus (T1D). Patients and healthy controls (HC) underwent optical coherence tomography (OCT) and OCT-angiography (OCTA). Individual macular layers, peripapillary retinal nerve fiber layer (pRNFL), and vascular parameters (vessel area density (VAD), vessel length fraction (VLF) and vessel diameter index (VDI)) of macular superficial vascular (SVP), intermediate (ICP), deep (DCP) and radial peripapillary capillary plexuses (RPCP) were quantified. Thirty-nine patients (5 with (DR group) and 34 without (noDR group) diabetic retinopathy) and 20 HC were enrolled. The pRNFL and ganglion cell layer (GCL) were thicker in noDR compared to HC and DR, reaching statistically significant values versus HC for some sectors. At the macular level, VAD and VLF were reduced in DR versus HC in all plexuses, and versus noDR in SVP (p < 0.005 for all). At the RPCP level, VAD and VDI were increased in noDR versus HC, significantly for VDI (p = 0.0067). Glycemic indices correlated to retinal parameters. In conclusion, in T1D adolescents, retinal capillary and neuronal changes are present after long-lasting disease, even in the absence of clinical DR. These changes modify when clinical retinopathy develops. The precocious identification of specific OCT and OCTA changes may be a hallmark of subsequent overt retinopathy.

Hyper-Reflecting Foci in Multiple Sclerosis Retina Associate With Macrophage/Microglia-Derived Cytokines in Cerebrospinal Fluid.

Background: Increasing evidence suggests that retinal hyper-reflecting foci (HRF) might be clusters of activated and proliferating microglia. Since microglia are widespread activated in multiple sclerosis (MS) brain, its evaluation in retina may help to understand and monitor MS-related pathology. Aim: This study aims at investigating the association of HRF with cerebrospinal fluid (CSF) cytokines and MRI parameters in relapsing-remitting MS (RRMS). Methods: Nineteen RRMS at clinical onset and 15 non-inflammatory neurological disorders (NIND) underwent brain 3T MRI and CSF examination. Optical coherence tomography (OCT) analysis, including HRF count, was performed on RRMS patients. Sixty-nine cytokines/chemokines were analyzed in the CSF by multiplex technology. Results: In RRMS, HRF count in the ganglion cell layer (GCL) was associated with IL-1Ra, IL-9, IL-15, IFN-γ, and G-CSF. Moreover, in RRMS patients CSF concentrations of IL-1Ra and G-CSF associated with global cortical thickness. The HRF count in the inner nuclear layer (INL) correlated with IL-22, IL-34, IL-35, CXCL-2, CXCL-10, and CXCL-13, and multivariate analysis confirmed a strong association (r2: 0.47) with both CXCL-2 (ß: -0.965, p = 0.0052) and CXCL-13 (ß: 0.241, p = 0.018). This latter cytokine increased in RRMS with high HRF count compared with NIND and RRMS with low HRF count. Finally, the CXCL-13/CXCL-2 ratio strongly associated with HRF count (r: 0.8, p < 0.005) and cortical lesion volume (r: 0.5, p < 0.05). Conclusions: The association of HRF with intrathecally produced monocyte/microglia-derived cytokines confirms their microglial origin and indicates they are worth further evaluating as markers of activated microglia.

Retinal Hyperreflecting Foci Associate With Cortical Pathology in Multiple Sclerosis.

BACKGROUND AND OBJECTIVES: Microglia, the resident immune cell of the brain and retina, is widespread activated in the white and gray matter (GM) in multiple sclerosis (MS). The objective of this study is to evaluate the presence and number of hyperreflecting foci (HRF), considered clusters of activated and proliferating retinal microglia, and their association with clinical and radiologic disease parameters in relapsing-remitting MS (RRMS). METHODS: At baseline, 80 patients with RRMS underwent optical coherence tomography (OCT) and 3T-MRI (including 3-dimensional T1, fluid-attenuated inversion recovery, and double inversion recovery sequences), closed to their disease onset (6.3 ± 5.1 months). These patients were then clinically and radiologically followed up for a mean of 43 months, evaluating the no evidence of disease activity (NEDA) condition, further divided into clinical (cNEDA) and radiologic (rNEDA). Patients with a clinical history or MRI/OCT findings suggestive of optic neuritis (ON) were excluded from the study. RESULTS: Compared with healthy controls, the HRF number was significantly higher in the inner nuclear layer (INL) of patients with RRMS (19.55 ± 5.65 vs 13.84 ± 2.57, p < 0.001) and associated with INL volume (ß: 1.21, p < 0.001). GM lesion volume significantly correlated with the INL HRF count (p = 0.008). Survival analysis revealed a significant association between INL HRF and both cNEDA (p = 0.017) and rNEDA (p = 0.002). DISCUSSION: We found a strong association between retinal microglial proliferation and cortical pathology in RRMS, a finding suggesting a possible underlying common immunopathologic mechanism. Furthermore, microglial activation at baseline was observed to predict subsequent inflammatory events, indicating that HRF might be a candidate prognostic biomarker worthy of further investigation. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that in patients with early RRMS but without ON, the number of HRF on OCT of the retinal inner nuclear layer is associated with cNEDA and rNEDA.

Handheld Fundus Camera for Diabetic Retinopathy Screening: A Comparison Study with Table-Top Fundus Camera in Real-Life Setting.

The aim of the study was to validate the performance of the Optomed Aurora® handheld fundus camera in diabetic retinopathy (DR) screening. Patients who were affected by diabetes mellitus and referred to the local DR screening service underwent fundus photography using a standard table-top fundus camera and the Optomed Aurora® handheld fundus camera. All photos were taken by a single, previously unexperienced operator. Among 423 enrolled eyes, we found a prevalence of 3.55% and 3.31% referable cases with the Aurora® and with the standard table-top fundus camera, respectively. The Aurora® obtained a sensitivity of 96.9% and a specificity of 94.8% in recognizing the presence of any degree of DR, a sensitivity of 100% and a specificity of 99.8% for any degree of diabetic maculopathy (DM) and a sensitivity of 100% and specificity of 99.8% for referable cases. The overall concordance coefficient k (95% CI) was 0.889 (0.828-0.949) and 0.831 (0.658-1.004) with linear weighting for DR and DM, respectively. The presence of hypertensive retinopathy (HR) was recognized by the Aurora® with a sensitivity and specificity of 100%. The Optomed Aurora® handheld fundus camera proved to be effective in recognizing referable cases in a real-life DR screening setting. It showed comparable results to a standard table-top fundus camera in DR, DM and HR detection and grading. The Aurora® can be integrated into telemedicine solutions and artificial intelligence services which, in addition to its portability and ease of use, make it particularly suitable for DR screening.

Case Report: Multiple Retinal Astrocytic Hamartomas in Congenital Disorder of Glycosylation-Ia.

Congenital disorder of glycosylation-Ia (CDG-Ia) is a rare autosomal recessive genetic disorder, characterized by systemic and ophthalmological abnormalities. Here, we report multiple retinal astrocytic hamartomas as a new retinal finding in an adolescent affected by congenital disorder of CDG-Ia. A 15-year-old boy affected by CDG-Ia underwent full ophthalmic examination, full field electroretinography (ERG) evaluation and retinal multimodal imaging, including: fundus photography, spectral domain optical coherence tomography (SD-OCT) and blue fundus autofluorescence (FAF). Blue FAF showed multiple papillary and iuxtapapillary bilateral hyper-FAF lesions, corresponding to hyperreflective thickening of the retinal nerve fiber layer, with internal optical empty spaces and posterior dense optical shadowing at SD-OCT. These imaging findings were consistent with retinal astrocytic hamartomas. Scotopic ERG response was significantly reduced in both eyes. Macular edema and absence of the retinal outer segments layer were also detectable. Retinal multi-modal imaging provides additional insights about retinal involvement of patients affected by CDG-Ia. In particular, this case shows the presence of multiple retinal astrocytic hamartomas.

RETINAL DYSTROPHY IN JEUNE SYNDROME: A MULTIMODAL IMAGING CHARACTERIZATION.

PURPOSE: To report multimodal imaging findings in a patient affected by Jeune syndrome-associated retinal dystrophy. METHODS: Observational case report. RESULTS: An 18-year-old girl affected by Jeune syndrome was referred to our low vision unit. She presented with bilateral high myopia, reduced visual acuity, exotropia, and nystagmus. Fundus examination detected posterior myopic staphyloma and diffuse retinal dystrophy confirmed using a full-field electroretinogram as a cone-rod dystrophy. Spectral domain optical coherence tomography detected a thick anomalous hyperreflective band located beneath an irregular and disrupted external limiting membrane, showing the primary involvement of the photoreceptors outer segment with relative sparing of the retinal pigment epithelium, as confirmed by fundus autofluorescence. CONCLUSION: This is a case of Jeune syndrome with retinal abnormalities studied with fundus autofluorescence and optical coherence tomography. Retinal noninvasive multimodal imaging could provide significant insight in the retinal involvement of patients affected by Jeune syndrome and should have an essential role in the multidisciplinary diagnostic approach and follow-up.