Utility values and electronic device use in low-vision people attending rehabilitation services: Data from a nation-wide registry in Italy.

PURPOSE: To estimate utility values associated with visual loss using EuroQol (EQ-5D) questionnaire, the impact of low-vision (LV) device use on utilities and the contribution of Instrumental Activities of Daily Living (IADL) score in patients attending vision rehabilitation (VR) services enrolled in the Italian Device & Aids Register (D.A.Re). METHODS: This is a multicenter, prospective, cross-sectional study. D.A.Re. collects general and clinical information, vision-specific variables, use of electronic devices and quality of life questionnaires. RESULTS: A total of 442 patients (75.0±16.6 years, 275 female) were included, 88 (19.9%) used specialised electronic LV devices, and 116 (26.2%) used smartphones and tablets. Users of smartphones and tablets were younger than non-users (67.5 vs. 77.6 years, p<0.001), but overall, their age ranged between 20 and 93. Stronger associations were found between vision-specific variables and IADL score compared to EQ-5D score. In multivariable age-adjusted models, the utility value of using smartphones and tablets on EQ-5D score was 0.12 (p<0.01), slightly larger than that of 1.0 logMAR difference (-0.09, p<0.01) or visual field damage within 10° of fixation (-0.10, p<0.01). Use of portable low-vision electronic devices and being employed or student (vs. retired) was also associated with better utility values (0.12 and 0.15, respectively, p<0.05). CONCLUSIONS: Visual loss is associated with loss of utilities in Italian patients attending VR services, whereas special-purpose electronic aids, and smartphone and tablet use are associated with better utility values. We found that IADL may be more sensitive to visual loss than EQ-5D and could be a valid health-related quality of life outcome in trials on VR.

Whole Genome Sequencing Solves an Atypical Form of Bardet-Biedl Syndrome: Identification of Novel Pathogenic Variants of BBS9.

Bardet-Biedl syndrome (BBS) is a rare recessive multisystem disorder characterized by retinitis pigmentosa, obesity, postaxial polydactyly, cognitive deficits, and genitourinary defects. BBS is clinically variable and genetically heterogeneous, with 26 genes identified to contribute to the disorder when mutated, the majority encoding proteins playing role in primary cilium biogenesis, intraflagellar transport, and ciliary trafficking. Here, we report on an 18-year-old boy with features including severe photophobia and central vision loss since childhood, hexadactyly of the right foot and a supernumerary nipple, which were suggestive of BBS. Genetic analyses using targeted resequencing and exome sequencing failed to provide a conclusive genetic diagnosis. Whole-genome sequencing (WGS) allowed us to identify compound heterozygosity for a missense variant and a large intragenic deletion encompassing exon 12 in BBS9 as underlying the condition. We assessed the functional impact of the identified variants and demonstrated that they impair BBS9 function, with significant consequences for primary cilium formation and morphology. Overall, this study further highlights the usefulness of WGS in the diagnostic workflow of rare diseases to reach a definitive diagnosis. This report also remarks on a requirement for functional validation analyses to more effectively classify variants that are identified in the frame of the diagnostic workflow.

VITELLIFORM LESIONS ASSOCIATED WITH LEPTOCHOROID AND PSEUDODRUSEN.

OBJECTIVE: To characterize clinical and prognostic implications of leptovitelliform maculopathy (LVM), a distinctive phenotype of vitelliform lesion characterized by the coexistence of subretinal drusenoid deposits (SDD) and leptochoroid. DESIGN: Retrospective, cohort study. SUBJECTS: The study compares patients affected by leptovitelliform maculopathy with cohorts displaying a similar phenotypic spectrum. This includes patients with acquired vitelliform lesions (AVL) and those with SDD alone. METHODS: A total of 60 eyes of 60 patients were included, of whom 20 eyes had LVM, 20 eyes had AVL, and the remaining had SDD. Patients older than 50 years with complete medical records and multimodal imaging for at least 6 months of follow-up, including color fundus photograph (CFP) or MultiColor, optical coherence tomography (OCT), fundus autofluorescence (FAF), and OCT angiography (OCTA) were included. MAIN OUTCOME MEASURES: Choroidal vascularity index (CVI); proportion of late-stage complications (macular neovascularization, atrophy). RESULTS: The AVL subgroup exhibited a significantly higher CVI compared to both LVM (p<0.001) and SDD subgroups (p<0.001). The proportion of late-stage complications significantly differed among subgroups (χ2=7.5, p=0.02). Eyes with LVM presented the greatest proportion of complications (55%) after a mean of 29.3 months, while the remaining eyes presented a similar proportion of complications, including 20% in AVL after 27.6 months and 20% in SDD after 36.9 months. Kaplan-Meier estimates of survival demonstrated a significant difference in atrophy development between groups (p<0.001), with a median survival of 3.9 years for LVM and 7.1 years for controls. The presence of LVM correlated with a fourfold increase in the likelihood of developing complications. CONCLUSIONS: Leptovitelliform maculopathy, characterized by the association of vitelliform lesions with SDD and leptochoroid, represents a distinct clinical phenotype in the broader spectrum of vitelliform lesions. The importance of a clinical distinction for these lesions is crucial due to a higher propensity for faster progression and an elevated rate of complications, particularly toward atrophic conversion.

The "triple-layer sign": an optical coherence tomography signature for the detection of non-exudative macular neovascularization.

PURPOSE: To assess the sensitivity and specificity of the "triple layer sign" (TLS) (retinal pigment epithelium (RPE), neovascular tissue, and Bruch's membrane) on structural optical coherence tomography (OCT) images for the diagnosis of treatment-naïve non-exudative type-1 macular neovascularization (NE-MNV) in age-related macular degeneration (AMD). DESIGN: Cross-sectional study. METHODS: Two masked retinal experts evaluated the presence of the TLS in eyes with NE-MNV and controls with an RPE elevation without exudation due to other causes than NE-MNV in AMD [e.g., medium-large drusen, cuticular drusen, basal laminar deposits (BlamD)]. RESULTS: 130 eyes of 98 consecutive patients met the study criteria; 40 eyes of 40 patients satisfied the criteria for being included in the NE-MNV secondary to AMD group (27 females, 13 males, with a mean age of 73.8 ± 8.0 years), and 90 eyes of 58 patients met the criteria to be included in the control group (31 eyes were included in the medium-to-large drusen sub-group, 32 eyes in the cuticular drusen sub-group, and 27 eyes in the BlamD group. The TLS was observed in 39/40 patients with NE-MNV and 8/90 controls. The sensitivity and specificity of the TLS for the diagnosis of NE-MNV were 97% and 91%, respectively. CONCLUSIONS: The TLS on OCT demonstrated high sensitivity and specificity values in detecting treatment-naive type 1 NE-MNV.

LeptoVitelliform Maculopathy: delineating a distinct clinical entity from acquired vitelliform lesions.

OBJECTIVES: To characterize acquired vitelliform lesions associated with leptochoroid (i.e., diffuse choroidal thinning) and reticular pseudodrusen (RPD) and compare this phenotype to the acquired vitelliform lesion (AVL) in the dystrophic spectrum. METHODS: This retrospective, observational case-control study enrolled 56 patients (56 eyes) affected by vitelliform lesions (AVL), including 27 patients with AVL associated with RPD and leptochoroid (i.e., choroidal thinning) referred to as LeptoVitelliform Maculopathy (LVM), and 29 AVL patients without other funduscopic abnormalities. The main structural features analysed were the integrity of the external limiting membrane (ELM), ellipsoid zone (EZ), and retinal pigment epithelium (RPE), the presence of hyporeflective spaces, and hypertransmission. Choroidal vascular index (CVI) was calculated using ImageJ software. RESULTS: Patients with LVM were 6.69 years older and presented smaller vitelliform lesions considering both vertical (P < 0.001) and horizontal diameters (P < 0.001) with a similar visual impairment compared to the AVL group (P = 0.27). The LVM subgroup showed a greater alteration of the ELM (p < 0.001) and choroidal hypertransmission (i = 0.007), accompanied by less frequent RPE bumps (P = 0.001) and hyporeflective spaces within the vitelliform material (P = 0.002). Furthermore, the LVM group presented a lower CVI with a significant attenuation on both the luminal and stromal compartments compared to AVL (P < 0.001, both). CONCLUSIONS: The phenotypic combination of subretinal vitelliform lesion and RPD may delineate a distinct phenotype that shares with AVL only the presence of vitelliform material and a similar visual deterioration. The presented findings of LVM highlight significant structural and microvascular alterations that may hold prognostic relevance, warranting future longitudinal studies.

Advancements in Imaging and Therapeutic Options for Dry Age-Related Macular Degeneration and Geographic Atrophy.

Age-related macular degeneration (AMD) is a leading cause of vision loss in the elderly, with dry AMD (d-AMD) leading to geographic atrophy (GA) and significant visual impairment. Multimodal imaging plays a crucial role in d-AMD diagnosis and management, allowing for detailed classification of patient phenotypes and aiding in treatment planning and prognosis determination. Treatment approaches for d-AMD have recently witnessed profound change with the development of specific drugs targeting the complement cascade, with the first anticomplement agents recently approved for GA treatment. Additionally, emerging strategies such as gene therapy and laser treatments may offer potential benefits, though further research is needed to fully establish their efficacy. However, the lack of effective therapies capable of restoring damaged retinal cells remains a major challenge. In the future, genetic treatments aimed at preventing the progression of d-AMD may emerge as a powerful approach. Currently, however, their development is still in the early stages.

Multimodal imaging in diabetic retinopathy and macular edema: An update about biomarkers.

Diabetic macular edema (DME), defined as retinal thickening near, or involving the fovea caused by fluid accumulation in the retina, can lead to vision impairment and blindness in patients with diabetes. Current knowledge of retina anatomy and function and DME pathophysiology has taken great advantage of the availability of several techniques for visualizing the retina. Combining these techniques in a multimodal imaging approach to DME is recommended to improve diagnosis and to guide treatment decisions. We review the recent literature about the following retinal imaging technologies: optical coherence tomography (OCT), OCT angiography (OCTA), wide-field and ultrawide-field techniques applied to fundus photography, fluorescein angiography, and OCTA. The emphasis will be on characteristic DME features identified by these imaging technologies and their potential or established role as diagnostic, prognostic, or predictive biomarkers. The role of artificial intelligence in the assessment and interpretation of retina images is also discussed.

DEEP LEARNING FOR AUTOMATIC PREDICTION OF EARLY ACTIVATION OF TREATMENT-NAIVE NONEXUDATIVE MACULAR NEOVASCULARIZATIONS IN AGE-RELATED MACULAR DEGENERATION.

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

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

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

Macular Neovascularization Secondary to Subclinical Angioid Streaks in Age-Related Macular Degeneration: Treatment Response to Anti-VEGF at 2-Year Follow-up.

INTRODUCTION: To characterize the response to antivascular endothelial growth factor (VEGF) treatment of macular neovascularization (MNV) secondary to age-related macular degeneration (AMD) with subclinical angioid streaks (AS) during a 2-year follow-up. METHODS: Retrospective, longitudinal, case-control, and multicentric study. Among a cohort of neovascular AMD population, we selected patients with subclinical AS and treatment-naïve MNV treated with anti-VEGF for a 2-year follow-up. An age- and sex-matched control group with treatment-naïve MNV secondary to AMD without subclinical AS was selected. Demographics and differences in treatment response (i.e., number of injections needed, anatomical and functional outcomes) between the two groups were analyzed. RESULTS: Among 102 eyes of 102 patients with neovascular AMD, 34 eyes of 34 patients (82 ± 6 years old) were included in the subclinical AS group, whereas 68 eyes of 68 patients (81 ± 6 years old, p = 0.342) in the control group. All eyes with subclinical AS presented RPD compared to 56% of eyes without subclinical AS (p < 0.001). During the 2-year follow-up, eyes with subclinical AS needed more injections (10.6 ± 3.2 vs 8.3 ± 3.1 injections for eyes with and without subclinical AS, respectively, p < 0.001). Visual acuity (VA) decreased during the treatment (from 0.53 ± 0.37 at the baseline to 0.69 ± 0.45 LogMAR at 2-year follow-up, p = 0.044) in eyes with subclinical AS; no VA changes were observed in the control group (p = 0.798). RPE atrophy at the end of the 2-year follow-up affected 74% of cases with subclinical AS and 29% of cases of the control group (p < 0.001). CONCLUSIONS: MNVs secondary to AMD with subclinical AS are characterized by worse functional and anatomical outcomes after 2-year anti-VEGF treatment compared to MNV secondary to AMD without subclinical AS, supporting the different pathophysiological mechanisms involved in this recently described AMD phenotype.

Rationale and Design of VOYAGER: Long-term Outcomes of Faricimab and Port Delivery System with Ranibizumab for Neovascular Age-Related Macular Degeneration and Diabetic Macular Edema in Clinical Practice.

Purpose: To describe the rationale and design of the VOYAGER (NCT05476926) study, which aims to investigate the safety and effectiveness of faricimab and the Port Delivery System with ranibizumab (PDS) for neovascular age-related macular degeneration (nAMD) or diabetic macular edema (DME) in clinical practice. VOYAGER also aims to understand drivers of clinical practice treatment outcomes by gaining novel insight into the intersection of treatment regimens, decisions, anatomic outcomes, and vision. Design: Primary data collection, noninterventional, prospective, multinational, multicenter clinical practice study. Participants: At least 5000 patients initiating/continuing faricimab or PDS for nAMD/DME (500 sites, 31 countries). Methods: Management will be per usual care, with no mandated scheduled visits/imaging protocol requirements. Using robust methodologies, relevant clinical and ophthalmic data, including visual acuity (VA), and data on treatment clinical setting/regimens/philosophies, presence of anatomic features, and safety events will be collected. Routinely collected fundus images will be uploaded to the proprietary Imaging Platform for analysis. An innovative investigator interface will graphically display the patient treatment journey with the aim of optimizing treatment decisions. Main Outcome Measures: Primary end point: VA change from baseline at 12 months per study cohort (faricimab in nAMD and in DME, PDS in nAMD). Secondary end points: VA change over time and per treatment regimens (fixed, treat-and-extend, pro re nata, and other) and number. Exploratory end points: VA change in relation to presence/location of anatomic features that impact vision (fluid, central subfield thickness, fibrosis, atrophy, subretinal hyperreflective material, diabetic retinopathy severity, and disorganization of retinal inner layers) and per treatment regimen/philosophies. The impact of regional and practice differences on outcomes will be assessed as will safety. Results: Recruitment commenced in November 2022 and will continue until late 2027, allowing for up to 5 years follow-up. Exploratory interim analyses are planned annually. Conclusions: VOYAGER is an innovative study of retinal diseases that will assess the effectiveness and safety of faricimab and PDS in nAMD and DME and identify clinician- and disease-related factors driving treatment outcomes in clinical practices globally to help optimize vision outcomes. Financial Disclosures: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

NONEXUDATIVE INTRARETINAL FLUID IN INTERMEDIATE AGE-RELATED MACULAR DEGENERATION.

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

Use of the Patient Health Questionnaire-9 (PHQ-9) and Generalized Anxiety Disorder-7 (GAD-7) questionnaires for clinical decision-making and psychological referral in ophthalmic care: a multicentre observational study.

OBJECTIVES: The aim of this study was to evaluate the influence of anxiety and depression on clinician decision-making in patients suffering from chronic eye disease in ophthalmological clinical practice. DESIGN AND SETTING: This multicentre observational study, in collaboration with the WHO, included ophthalmologists and their patients affected by chronic eye disease. States of anxiety and depression were screened with specific questionnaires, the Patient Health Questionnaire-9 (PHQ-9) and Generalized Anxiety Disorder-7 (GAD-7), self-administered by patients before the visit. In the present analysis, we report data from three major eye care centres in Italy between 2021 and 2022. PRIMARY AND SECONDARY OUTCOMES: To assess self-reported changes in ophthalmologists' clinical approach (communication style and their clinical-therapeutic strategies) and decisions after knowing questionnaire scores (primary aim), and to analyse the PHQ-9 and GAD-7 scores in patients with chronic eye diseases (secondary aim). RESULTS: 41 ophthalmologists and 359 patients were included. The results from PHQ-9 and GAD-7 scores showed critical depression and anxiety status scores (PHQ-9 ≥5 and GAD-7 ≥10) in 258 patients. In 74% of cases, no actions were taken by the ophthalmologists based on these scores; in 26% of cases, they changed their clinical approach; and in 14% of cases, they referred the patients for psychological/psychiatric evaluation. CONCLUSIONS: States of anxiety and depression affect many patients with chronic eye conditions and need to be detected and managed early to improve patients' well-being. Providing ophthalmologists with knowledge of their patients' psychological conditions can change the clinical management and attitude towards referral for a psychological evaluation. Further studies are needed to expand our knowledge of how to raise awareness among ophthalmologists regarding multimorbidity of patients suffering from chronic eye diseases in order to achieve better clinical outcomes.

The Insulin-Degrading Enzyme from Structure to Allosteric Modulation: New Perspectives for Drug Design.

The insulin-degrading enzyme (IDE) is a Zn2+ peptidase originally discovered as the main enzyme involved in the degradation of insulin and other amyloidogenic peptides, such as the ß-amyloid (Aß) peptide. Therefore, a role for the IDE in the cure of diabetes and Alzheimer's disease (AD) has been long envisaged. Anyway, its role in degrading amyloidogenic proteins remains not clearly defined and, more recently, novel non-proteolytic functions of the IDE have been proposed. From a structural point of view, the IDE presents an atypical clamshell structure, underscoring unique enigmatic enzymological properties. A better understanding of the structure-function relationship may contribute to solving some existing paradoxes of IDE biology and, in light of its multifunctional activity, might lead to novel therapeutic approaches.

Use of electronic devices by people attending vision rehabilitation services in Italy: A study based on the device and aids registry (D.A.Re).

PURPOSE: To investigate the characteristics of electronic device users, specifically smartphones and tablets, in the Device & Aids Register (D.A.Re), from several low-vision rehabilitation services in Italy. METHODS: We collected general and clinical information about ocular and systemic diseases, visual function, reading speed and Instrumental Activities of Daily Living (IADL) questionnaire score. Technological details of each optical and electronic device, (including screen size, touch-screen and OCR functions, text-to-speech function) were also collected. RESULTS: 1218 patients (752 females and 466 males) were included in our analysis, mean age 71.5 (±18.8) years. Users of electronic aids (n.237) were slightly younger (67 vs 72 years, p < 0.001) than non-users (n.981), had a worse reading speed (38 vs 65 words/minute), critical print size (43 vs 28 print size, p < 0.001), poorer visual acuity (VA)(1.0 logMAR or less: 30% non-users vs 73% users, p < 0.001) and more commonly visual field restriction within 10° (23% vs 14%, p = 0.001). A similar proportion of users and non-users were retired (about 70%) and about 16-17% were employed. The use of portable electronic devices (5″or less, p < 0.001; 6″ to 18″ screen size, p = 0.017) was associated with better IADL scores, and the use of stand devices with worse IADL score (p < 0.001); Furthermore, using smartphones and tablets (193 subjects) was strongly associated with better IADL scores. CONCLUSION: We found that using electronic devices, and especially smartphone and tablets, were associated with better vision-related quality of life in low-vision people attending rehabilitation services. While this association does not mean causality, these findings seemed robust to confounder adjustment.

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

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

Polytherapy and Multimorbidity Pattern of Users of Anti-VEGF Drugs and Dexamethasone for the Treatment of Age-Related Macular Degeneration and other Vascular Retinopathies in Clinical Practice.

Introduction: Our aim was to describe the polytherapy and multimorbidity pattern of users of anti-VEGF and dexamethasone drugs for the treatment of these conditions, and to investigate their polytherapy and multimorbidity profiles, together with adherence and the burden of care. Methods: Descriptive, population-based, pharmacoepidemiology study on the users of anti-VEGF drugs, and secondarily intravitreal dexamethasone, for the treatment of age-related macular degeneration and other vascular retinopathies in clinical practice, using administrative databases of Lazio region, Italy. We used a cohort of 50,000 residents in Lazio in 2019 with same age as comparison. Polytherapy was assessed using databases of prescribed drugs intended for outpatient use. Multimorbidity was investigated with additional sources, such as hospital discharge records, outpatient care records, and disease-specific exemptions from co-payment. Each patient was followed for 1 to 3 years from the first intravitreal injection received. Results: 16,266 residents in Lazio who received the first IVI from 1 January 2011 to 31 December 2019, with at least 1 year of observation before index date, were included. The proportion of patients with at least one comorbidity was 54.0%. Patients used an average 8.6 (SD 5.3) concomitant drugs other than anti-VEGF used for injections. A large percentage of patients (39.0%) used 10 or more concomitant drugs, including antibacterials (62.9%), drugs for peptic ulcers (56.8%), anti-thrombotics (52.3%), NSAIDs (44.0%), and anti-dyslipidaemics (42.3%). The same proportions were found across patients of all ages, probably due to high prevalence of diabetes (34.3%), especially in younger age groups. When stratified by diabetes, a comparison of multimorbidity and polytherapy with a sample of 50,000 residents of the same age found that patients receiving IVIs used more drugs and had more comorbidities, particularly in non-diabetics. Lapses of care, whether short (absence of any type of contact for at least 60 days in the first year of follow-up and 90 in the second year) or long (90 days in the first and 180 days in the second year) were common: 66% and 51.7%, respectively. Conclusions: Patients receiving intravitreal drugs for retinal conditions have high multimorbidity and polytherapy rates. Their burden of care is aggravated by the large number of contacts with the eye care system for examinations and injections. Pursuing Minimally Disruptive Medicine to optimise patient care is a difficult goal for health systems, and more research on clinical pathways and their implementation is warranted.

Progression Biomarkers of Microvascular and Photoreceptor Changes Upon Long-Term Evaluation in Type 1 Diabetes.

Purpose: To assess demographic, metabolic, and imaging predictors influencing microvasculature and photoreceptors changes over a 4-year follow-up in type 1 diabetes mellitus (DM1). Methods: This prospective cohort study enrolled patients with DM1 with mild non-proliferative diabetic retinopathy. Complete medical records, glycosylated hemoglobin (HbA1c), optical coherence tomography angiography, and adaptive optics were collected for the 4 years of follow-up. The main outcome measures included perfusion density at the superficial capillary plexus (SCP) and deep capillary plexus (DCP), choriocapillaris (CC) flow deficits (FDs, %), cone density, linear dispersion index (LDi), and heterogeneity packing index (HPi). Results: The SCP presented a dichotomic perfusion trend, with increasing PD at 1 and 2 years and a subsequent decline (P < 0.001). DCP presented a similar trend in the first 2 years (P < 0.01) but not at the following time points, whereas CC FDs constantly increased over time (P < 0.01). The best-fitted model for the microvascular parameters demonstrated that the main factors affecting SCP included time (P < 0.001), duration of diabetes (P = 0.007), and HbA1c (P = 0.03), whereas the DCP was influenced by LDi modifications (P = 0.006). The LDi and HPi were mainly influenced by SCP and CC perfusion in the parafovea (P = 0.02). Conclusions: This study demonstrated an initial vasodilatory phenomenon resulting from a compensatory mechanism from the superficial vasculature, followed by capillary dropout. Initially, it would seem that there was an adaptive response by the DCP to the needs of the photoreceptors. Although the SCP may initially support the DCP, when the microvascular damage becomes diffuse and involves the SCP and CC it directly affects photoreceptor integrity.

Prognostic Imaging Biomarkers in Diabetic Macular Edema Eyes Treated with Intravitreal Dexamethasone Implant.

BACKGROUND: The aim was to evaluate predictive value of baseline optical coherence tomography (OCT) and OCT angiography (OCTA) parameters in diabetic macular edema (DME) treated with dexamethasone implant (DEXi). METHODS: OCT and OCTA parameters were collected: central macular thickness (CMT), vitreomacular abnormalities (VMIAs), intraretinal and subretinal fluid (mixed DME pattern), hyper-reflective foci (HRF), microaneurysms (MAs) reflectivity, ellipsoid zone disruption, suspended scattering particles in motion (SSPiM), perfusion density (PD), vessel length density, and foveal avascular zone. Responders' (RES) and non-responders' (n-RES) eyes were classified considering morphological (CMT reduction ≥ 10%) and functional (BCVA change ≥ 5 ETDRS letters) changes after DEXi. Binary logistic regression OCT, OCTA, and OCT/OCTA-based models were developed. RESULTS: Thirty-four DME eyes were enrolled (18 treatment-naïve). OCT-based model combining DME mixed pattern + MAs + HRF and OCTA-based model combining SSPiM and PD showed the best performance to correctly classify the morphological RES eyes. In the treatment-naïve eyes, VMIAs were included with a perfect fit for n-RES eyes. CONCLUSION: The presence of DME mixed pattern, a high number of parafoveal HRF, hyper-reflective MAs, SSPiM in the outer nuclear layers, and high PD represent baseline predictive biomarkers for DEXi treatment responsiveness. The application of these models to treatment-naïve patients allowed a good identification of n-RES eyes.