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.

Deep learning for automatic prediction of early activation of treatment naïve non-exudative MNVs in AMD.

BACKGROUND: Around 30% of non-exudative macular neovascularizations(NE-MNVs) exudate within 2 years from diagnosis in patients with age-related macular degeneration(AMD).The aim of the study is to develop a deep learning classifier based on optical coherence tomography(OCT) and OCT angiography(OCTA) to identify NE-MNVs at risk of exudation. METHODS: AMD patients showing OCTA and fluorescein angiography (FA) documented NE-MNV with a 2-years minimum imaging follow-up were retrospectively selected. Patients showing OCT B-scan-documented MNV exudation within the first 2 years formed the EX-GROUP while the others formed QU-GROUP.ResNet-101, Inception-ResNet-v2 and DenseNet-201 were independently trained on OCTA and OCT B-scan images. Combinations of the 6 models were evaluated with major and soft voting techniques. RESULTS: Eighty-nine (89) 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 3 single convolutional neural networks(CNNs).The major voting model resulting from the association of the 3 different CNNs resulted in improvement of performance both for OCTA and OCT B-scan (both significantly higher than human graders' performance). 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 enface imaging were more prevalent in QU GROUP. CONCLUSIONS: Artificial intelligence shows high performances in identifications of NE-MNVs 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 (OCT) phenotypes preceding atrophy related to age-related macular degeneration (AMD) on the progression of atrophic lesions. METHODS: In this observational retrospective cohort study, a total of 70 eyes of 60 consecutive patients with intermediate AMD 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.Main outcome measures were geographic atrophy (GA) progression rate (mm2/year) and square root-transformation GA (mm2/year). RESULTS: The best-fit model for GA (OR: 1.81, p<0.001) and square root-transformation GA (OR: 1.36, p<0.001) areas revealed that the main baseline predictor was the presence of an RPE-basal lamina-(BL)-Bruch's membrane (BrM) splitting. Large drusen at baseline appeared protective for the GA area lesion expansion over time (OR: 0.52, p<0.001) when considered with other confounders. CONCLUSION: A thin RPE-BL-BrM splitting without evidence of neovascularization on OCT angiography likely represents an OCT signature for late basal laminar deposits. Identifying this phenotype can help identify individuals with a higher risk of rapid progression and atrophy expansion.

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.

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.

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.

Nascent Geographic Atrophy as a Predictor of Type 3 Macular Neovascularization Development.

PURPOSE: To investigate the association of nascent geographic atrophy (GA) preceding the development of exudative type 3 macular neovascularization (MNV) in patients with age-related macular degeneration (AMD). DESIGN: Retrospective longitudinal study. PARTICIPANTS: Patients with AMD diagnosed with treatment-naive exudative type 3 MNV in 1 or both eyes were evaluated. Inclusion criteria included serial tracked structural OCT examinations for ≥ 2 years before the detection of exudative type 3 MNV. METHODS: Clinical characteristics and retinal imaging, including structural OCT at baseline and at each follow-up examination, were analyzed. Eyes showing the presence of nascent GA during the follow-up were selected for analysis of prevalence, and clinical characteristics at the site of subsequent type 3 MNV development. MAIN OUTCOME MEASURES: Description of the prevalence and clinical characteristics of nascent GA at the site of subsequent type 3 MNV development. RESULTS: Overall, 97 eyes affected by type 3 MNV meeting inclusion criteria were analyzed. Of 97 eyes (71 patients), 22 eyes of 21 patients (mean age 82 ± 9 years) showed nascent GA preceding exudative type 3 MNV. The observed prevalence of nascent GA preceding exudative type 3 MNV was 22.7% (95% confidence interval, 14.4%-31.0%). Exudative type 3 MNV developed a mean of 9 ± 6 months after detection of nascent GA. The presence of reticular pseudodrusen in the study eye did not significantly influence the timing of exudative type 3 MNV development after the observation of nascent GA (P > 0.1 in all analyses). Reduced best-corrected visual acuity was recorded at the exudative type 3 stage in comparison with the nascent GA stage (P = 0.003). CONCLUSIONS: As nascent GA may precede the development of exudative type 3 MNV, the detection of nascent GA in eyes with AMD may warrant closer surveillance to identify early exudative type 3 MNV warranting treatment. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.

SUBRETINAL LIPID GLOBULES AN EARLY BIOMARKER OF MACULAR NEOVASCULARIZATION IN EYES WITH INTERMEDIATE AGE-RELATED MACULAR DEGENERATION.

PURPOSE: To explore the association between subretinal lipid globules (SLGs) detected in eyes with intermediate age-related macular degeneration with the presence of nonexudative macular neovascularization. METHODS: This was a retrospective analysis of 113 consecutive patients with bilateral intermediate age-related macular degeneration (226 eyes) followed for a least 6 months. All eyes underwent multimodal imaging with fundus autofluorescence, spectral-domain optical coherence tomography, and optical coherence tomography angiography. Subretinal lipid globules were identified on spectral-domain optical coherence tomography as round hyporeflective lesions measuring 31 to 157 µ m located between the ellipsoid zone and the retinal pigment epithelium/Bruch membrane complex. Nonexudative macular neovascularization was detected with optical coherence tomography angiography. The features of NE-MNV lesions detected in eyes with SLGs were compared with those in eyes without SLGs. RESULTS: Subretinal lipid globules were identified in 15 eyes of which 14 eyes (93.3%) demonstrated NE-MNV on optical coherence tomography angiography. In the remaining 98 eyes without SLGs, 18 (18.4%) displayed NE-AMD on optical coherence tomography angiography. The macular neovascularization area was larger in the SLG subgroup (+0.38 vs. +0.21 mm 2 , P = 0.008) and showed faster horizontal growth (+727 µ m, CI 95% 250.4, 1,205.4) than MNV in eyes without SLGs (+64.9 µ m, CI 95%, 24.3, 154) on optical coherence tomography B-scans. After a mean of 11.6 months, the conversion rate to exudative MNV was similar between eyes with SLGs and those without SLGs [8/26 (38.5%) versus 3/13 (27.3%), P = 0.56)]. CONCLUSION: The detection of SLGs in eyes with intermediate age-related macular degeneration was strongly correlated with the presence of NE-MNV. Although these MNV lesions were larger and grew faster than NE-MNV detected in eyes lacking SLGs, the rates of conversion to exudative MNV appeared similar.

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.

In vivo assessment of associations between photoreceptors structure and macular perfusion in type 1 diabetes.

PURPOSE: To explore the potential relationships between macular vascular network and different adaptive optics (AO) metrics in patients with type 1 diabetes mellitus (DM1) with no signs (NoDR) or mild non-proliferative diabetic retinopathy (NPDR). DESIGN: Observational cross-sectional study. METHODS: Forty eyes of consecutive patients with DM1 (12 NoDR and 28 NPDR) and 10 healthy age-matched control subjects were included. All patients and controls were imaged using AO retinal camera and PLEX Elite 9000 optical coherence tomography (OCT) angiography (OCTA). The AO outcome measures to evaluate the cone photoreceptor mosaic characteristics were as follows: (1) Cone density (CD); (2) Linear Dispersion Index (LDi) and (3) Heterogeneity Packing Index (HPi). The OCTA outcome measures included: (1) superficial capillary plexus (SCP) perfusion density (PD); (2) deep capillary plexus (DCP) PD and (3) the choriocapillaris (CC) flow deficit percentage (FD%). RESULTS: NPDR group exhibited a close relationship between cone metrics and CC FD. Notably, CC FD% increase along with LDi (p=0.035), while the increasing CC FD% were associated with reducing CD (p=0.042) and the HPi (p=0.017). Furthermore, the OCTA parameters, including PD SCP and DCP, showed a significant negative correlation with CD. CONCLUSIONS: Our results demonstrated the relationship between macular perfusion at both retinal and choroidal levels and the cone mosaic in patients with DM1 interpolating swept-source-OCTA and AO metrics. In NPDR eyes, the photoreceptor damage was accompanied by CC insufficiency since the early stages of the disease.

Towards a better understanding of non-exudative choroidal and macular neovascularization.

Non-exudative macular and choroidal neovascularization (MNV and CNV) usually refers to the entity of treatment-naïve type 1 neovascularization in the absence of associated signs of exudation. Histopathological studies, dating back in the early 70s, identified the presence of non-exudative MNV, but the first clinical report of this finding was in the late 90s using indocyanine green angiography in eyes with age-related macular degeneration (AMD). With more advanced retinal imaging, there has been an ever increasing appreciation of non-exudative MNV associated with AMD and CNV with other macular disorders. However, consensus regarding the exact definition and the clinical management of this entity is lacking. Furthermore, there may be variation in the imaging features and clinical course suggesting that a spectrum of disease may exist. Herein, we review the large body of published work that has provided a better understanding of non-exudative MNV and CNV in the last decade. The prevalence, multimodal imaging features, clinical course, and response to treatment are discussed to elucidate further key insights about this entity. Based on these observations, this review also proposes a new theory about the origin and course of different sub-types of non-exudative MNV/CNV which can have different etiologies and pathways according to the clinical context of disease.

Ocular Biomarkers for Alzheimer Disease Dementia: An Umbrella Review of Systematic Reviews and Meta-analyses.

Importance: Several ocular biomarkers have been proposed for the early detection of Alzheimer disease (AD) and mild cognitive impairment (MCI), particularly fundus photography, optical coherence tomography (OCT), and OCT angiography (OCTA). Objective: To perform an umbrella review of systematic reviews to assess the diagnostic accuracy of ocular biomarkers for early diagnosis of Alzheimer disease. Data Sources: MEDLINE, Embase, and PsycINFO were searched from January 2000 to November 2021. The references of included reviews were also searched. Study Selection: Systematic reviews investigating the diagnostic accuracy of ocular biomarkers to detect AD and MCI, in secondary care or memory clinics, against established clinical criteria or clinical judgment. Data Extraction and Synthesis: The Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guideline checklist was followed and the Risk Of Bias in Systematic reviews tool was used to assess review quality. Main Outcomes and Measures: The prespecified outcome was the accuracy of ocular biomarkers for diagnosing AD and MCI. The area under the curve (AUC) was derived from standardized mean difference. Results: From the 591 titles, 14 systematic reviews were included (median [range] number of studies in each review, 14 [5-126]). Only 4 reviews were at low risk of bias on all Risk of Bias in Systematic Reviews domains. The imaging-derived parameters with the most evidence for detecting AD compared with healthy controls were OCT peripapillary retinal nerve fiber layer thickness (38 studies including 1883 patients with AD and 2510 controls; AUC = 0.70; 95% CI, 0.53-0.79); OCTA foveal avascular zone (5 studies including 177 patients with AD and 371 controls; AUC = 0.73; 95% CI, 0.50-0.89); and saccadic eye movements prosaccade latency (30 studies including 651 patients with AD/MCI and 771 controls; AUC = 0.64; 95% CI, 0.58-0.69). Antisaccade error was investigated in fewer studies (12 studies including 424 patients with AD/MCI and 382 controls) and yielded the best accuracy (AUC = 0.79; 95% CI, 0.70-0.88). Conclusions and Relevance: This umbrella review has highlighted limitations in design and reporting of the existing research on ocular biomarkers for diagnosing AD. Parameters with the best evidence showed poor to moderate diagnostic accuracy in cross-sectional studies. Future longitudinal studies should investigate whether changes in OCT and OCTA measurements over time can yield accurate predictions of AD onset.

Cortisol awake response imbalance as an indicator of acute central serous chorioretinopathy: Relationship with choriocapillaris and choroidal features.

Purpose: The purpose of the present study was to measure in central serous chorioretinopathy (CSC) the salivary cortisol awake response (CAR) delta percentage (Δ%) variation, a distinct and robust indicator of cortisol rhythm during wakefulness, commonly proposed as a marker of hypothalamic-pituitary adrenal (HPA) axis activity, whose alteration is frequently associated with several adverse health outcomes. Methods: In the present cross-sectional observational study, salivary CAR Δ% variation was assessed in 17 adult male subjects affected by acute naïve CSC and compared to 17 matched healthy controls. Choroid vasculature metrics were assessed in the study population by measuring the subfoveal choroidal thickness (FCT) and the choroidal vascularity index (CVI) by the imaging technique of enhanced-depth imaging spectral-domain optical coherence tomography (EDI-SD-OCT). Furthermore, flow signal void area features of the choriocapillaris were evaluated in the study population using OCT angiography (OCTA). Results: Both the control and CSC groups showed a physiological cortisol increase that occurred during the first 30 min after awaking. However, CSC adult male patients showed remarkably blunted CAR Δ% variation in comparison with controls, which might reflect a CSC-related imbalance of HPA axis activity. Statistically significant correlations were shown by Pearson's correlation test between salivary CAR Δ% and the selected choroidal and choriocapillaris imaging biomarkers (FCT, CVI, and flow signal void area) in the study population. Conclusion: In conclusion, alterations of the CAR Δ% increase, associated with choroidal-retinal metrics, might provide a window into the physiopathology of acute CSC, suggesting a possible common factor to explain the association between stress and CSC.

Biallelic Inactivating TUB Variants Cause Retinal Ciliopathy Impairing Biogenesis and the Structure of the Primary Cilium.

Inherited retinal degeneration (IRD) represents a clinically variable and genetically heterogeneous group of disorders characterized by photoreceptor dysfunction. These diseases typically present with progressive severe vision loss and variable onset, ranging from birth to adulthood. Genomic sequencing has allowed to identify novel IRD-related genes, most of which encode proteins contributing to photoreceptor-cilia biogenesis and/or function. Despite these insights, knowledge gaps hamper a molecular diagnosis in one-third of IRD cases. By exome sequencing in a cohort of molecularly unsolved individuals with IRD, we identified a homozygous splice site variant affecting the transcript processing of TUB, encoding the first member of the Tubby family of bipartite transcription factors, in a sporadic case with retinal dystrophy. A truncating homozygous variant in this gene had previously been reported in a single family with three subjects sharing retinal dystrophy and obesity. The clinical assessment of the present patient documented a slightly increased body mass index and no changes in metabolic markers of obesity, but confirmed the occurrence of retinal detachment. In vitro studies using patient-derived fibroblasts showed the accelerated degradation of the encoded protein and aberrant cilium morphology and biogenesis. These findings definitely link impaired TUB function to retinal dystrophy and provide new data on the clinical characterization of this ultra-rare retinal ciliopathy.

Effect of intravitreal dexamethasone implant in treatment-naive and previously-treated patients with diabetic macular edema.

PURPOSE: To document the effects of intravitreal dexamethasone implant on retinal microvasculature in patients with diabetic retinopathy complicated by center-involving macular edema. METHODS: 35 eyes of 35 patients affected by retinopathy due to type 2 diabetes (15 treatment-naïve and 20 previously treated) were included in this retrospective study with a follow-up of 4 months. Foveal avascular zone (FAZ) area and superficial capillary plexus (SCP) and deep capillary plexus (DCP) densities in the foveal and parafoveal areas were measured by optical coherence tomography angiography (OCTA) at baseline and 2 and 4 months post-injection. Intraocular pressure, morphological and functional parameters were evaluated. RESULTS: a significant difference was found in both groups at 2 months after injection in terms of functional (BCVA, p < 0.05) and morphological (CMT, p < 0.05) parameters. During follow-up, FAZ area, SCP, and DCP in the foveal and parafoveal areas did not change significantly. CONCLUSIONS: intravitreal dexamethasone implant is effective in the treatment of diabetic center-involving macular edema and was associated with significant improvements in BCVA and CMT at 2 months after injection. After a single dexamethasone implant injection, FAZ area and retinal vascular density does not show significant variations in both naive and non-naive DME patients subgroups.

Morpho-Functional Macular Assessment in a Case of Facioscapulohumeral Muscular Dystrophy: Photoreceptor Degeneration as Possible Cause for Reduced Visual Acuity over Three Years of Follow-Up.

BACKGROUND: Autosomal-dominant facioscapulohumeral muscular dystrophy (FSHD) is a muscular dystrophy with associated retinal abnormalities such as retinal vessel tortuosity, focal retinal pigment epithelium defect and large telangiectasia vessels. METHODS: Case report of an FSHD 16-year-old female referred for blurred vision in both eyes (20/40), evening fever and shoulder muscle weakness over the past month preceding assessment. A multimodal assessment including visual acuity (VA), microperimetry (MP), multifocal electroretinogram (mfERG), optical coherence tomography (OCT), fluorescein angiography (FA) and fundus autofluorescence (FAF) was performed. RESULTS: OCT showed pseudocyst macular abnormalities and disruption of the photoreceptor layer with no signs of macular ischemia/exudation. Macular function showed foveal impairment recorded by mfERG and MP as a reduction of the response amplitude density and retinal sensitivity, respectively. No medical treatment was prescribed. After three years, patient's VA slightly improved to 20/32. OCT showed resolution of bilateral pseudocyst macular changes and persistence of photoreceptor disruption. By contrast, mfERG recordings remained abnormal for impaired foveal function and microperimetry mean sensitivity was reduced as well. CONCLUSIONS: This multimodal assessment showed persistent VA impairment at three years follow-up associated to abnormal foveal function and reduced retinal sensitivity, with spontaneous resolution of morphological macular changes, suggesting a retinal neurodegenerative process on the basis of the disease.

Middle-Inner Macular Layers Dysfunction in a Case of Stellate Foveomacular Retinoschisis Detected by Abnormal Multifocal Photopic Negative Response Recordings.

We describe the macular morpho-functional assessment of a 65-year-old man affected by stellate nonhereditary idiopathic foveomacular retinoschisis (SNIFR), studied by visual field, SD-OCT, autofluorescence, full-field electroretinogram (ffERG), multifocal electroretinogram (mfERG) and multifocal Photopic Negative Response (mfPhNR) recordings. The typical presentation consists of the foveal appearance of radial cartwheel pattern for the splitting of the retinal layers at the level of the Henle fiber layer (HFL) and the outer plexiform layer (OPL), perfectly seen by Spectral Domain-Optical Coherence Tomography (SD-OCT). Despite a normal function of the outer retina of the peripheral and central retina evaluated by ffERG and mfERG respectively, we observed a reduced function of the retinal elements involved in the retinoschisis by recording mfPhNR that assesses mainly inner retina function (retinal ganglion cells and their axons). Therefore, it is likely that the observed impaired mfPhNR responses reflect the signaling defects derived from the delaminated middle retina and transmitted to the innermost retinal layers.

Impact of Intravitreal Anti-VEGF Therapy on Microperimetry of the Retinal Nonperfusion Areas of Patients with Proliferative Diabetic Retinopathy.

INTRODUCTION: This study assessed retinal nonperfusion area (NPA) changes after anti-VEGF treatment in proliferative diabetic retinopathy (PDR) eyes using swept-source widefield optical coherence tomography angiography (SS-WF OCTA) and investigated the relationships with the microperimetry (MP-1) functional changes observed in the same areas. METHODS: This was a single-center observational case series. Seven PDR eyes naïve to treatment that received three monthly intravitreal injections of aflibercept were included. All eyes were imaged with SS-WF OCTA and MP-1 at baseline (T0) and 1 month after the third injection (T1). The regions of interest (ROIs) with evidence of NPAs at T0 OCTA images were selected. Qualitative and quantitative [perfusion density (PD) and vessel length density (VLD)] OCTA vascular changes in the selected ROIs between T0 and T1 were compared with the corresponding MP-1 functional changes [mean sensitivity (MS)]. RESULTS: Twenty-five ROIs were selected. In 52% of the ROIs, an improvement in MS was observed at T1, which was associated with qualitative and quantitative improvement in 92.3% of NPAs by OCTA. In 32% of the ROIs, MS worsening was observed at T1, which was associated with qualitative and quantitative worsening in 75% of NPAs by OCTA. Positive correlations between MS and both PD and VLD were found. Fisher's test showed an association between the improvements in MP and VLD. CONCLUSIONS: An association between OCTA and MP-1 parameter changes was found. The concomitant functional and morphological improvement in half of the ROIs suggests that anti-VEGF treatment may promote retinal changes that result in a better functional response.