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Abstract 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.

Abstract 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

Optical Coherence Tomography (OCT) and Optical Coherence Tomography Angiography (OCTA) are pivotal imaging techniques in diagnosing and managing macular disorders, providing high-resolution cross-sectional images of the retina. Although OCT artifacts are often deemed undesirable, they can paradoxically offer valuable insights into retinal pathology. This review explores the potential of OCT and OCTA artifacts to serve as indicators of pathological correlates in various macular conditions. The study emphasizes the importance of recognizing and leveraging these artifacts to refine clinicopathologic correlates characterizing several macular disorders, including age-related macular degeneration, diabetic retinopathy, and retinal vascular occlusive disease. OCT artifacts can reflect the ultrastructure and composition of pathological features, and their recognition can thus expand the understanding of the pathogenesis and improve the diagnostic interpretation of macular disorders. With the widespread use of OCT and OCTA technologies, identifying artifacts with clinicopathologic significance is of paramount importance and may have significant implications for management and prognosis.

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 Disclosure(s): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

PurposeTo 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).MethodsThis 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.ResultsA 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, pConclusionsVisual 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.

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.

Abstract To describe a novel optical coherence tomography (OCT) signature resembling sub-retinal pigment epithelium (RPE) tubules (SRT) in non-neovascular age-related macular degeneration (AMD). Patients suffering from non-neovascular AMD with complete medical records and multimodal imaging were retrospectively revised in three different tertiary care centers. Multimodal imaging included color fundus photograph, spectral-domain OCT (Spectralis, Heidelberg Engineering, Germany), fundus autofluorescence, OCT angiography (RTVue XR Avanti, Optovue, Inc., Fremont, CA). A total of 7 eyes of 7 patients with drusenoid pigment epithelium detachment (PED) were consecutively analyzed. The sub-RPE tubules appeared as ovoidal structures with a hyperreflective contour and hyporeflective interior appreciable in the sub-RPE-basal lamina (BL) space on OCT B-scan. The anatomical location of the sub-RPE formations was lying above the Bruch’s membrane in 5/7 cases (71.4%) or floating in the sub-RPE-BL space in 2/7 cases (28.6%). En-face OCTA revealed a curvilinear tubulation-like structure corresponding to SRT without flow signal. Sub-RPE tubules represent a newly identified OCT signature observed in eyes with drusenoid PED. The presumed origin may include a variant of calcified structure or alternatively activated RPE cells with some residual BL or basal laminar deposits attracted to BrM for craving oxygen.

Key Points High glucose quickly induces an atypical NF-kB pro-inflammatory program. CamKII phosphorylation of Rpt6 subunit of the proteasome stimulates IkBα turnover and p65-p50 release. Inhibition of either CamkII or proteasome blocks this pathway.

Abstract Background Retinal artery occlusion is a vascular entity caused by the temporary blockage of retinal arterioles. Case presentation We present the case of a 57-year-old woman a partial visual loss in the right eye due to a cilioretinal artery occlusion. Ophthalmoscopy revealed a focal area of retinal whitening superior to the optic nerve in the right eye, while the left eye was within the limit. Retinal imaging, in particular optical coherence tomography angiography (OCTA), showed a capillary drop out of the superficial capillary plexus and the corresponding b-scan showed a round hyporeflective grey dot (optical empty) corresponding to the dark grey spot on the enface view at the level of the retinal whitening area. Conclusion Although the images did not allow the differentiation between vasospasm or retinal emboli, the OCTA imaging might help to identify and to caught in the act the specific region causing the retinal impairment. Also, the possible formation of small microcavity should be considered in case with branch retinal artery occlusion. The use of this new imaging technology might help to evaluate the efficacy of the therapy in vivo.

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 β-amyloid (Aβ) 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.

Abstract The aim of this study was to measure macular perfusion in patients with type 1 diabetes and no signs of diabetic retinopathy (DR) using volume rendered three-dimensional (3D) optical coherence tomography angiography (OCTA). We collected data from 35 patients with diabetes and no DR who had OCTA obtained. An additional control group of 35 eyes from 35 healthy subjects was included for comparison. OCTA volume data were processed with a previously presented algorithm in order to obtain the 3D vascular volume and 3D perfusion density. In order to weigh the contribution of different plexuses’ impairment to volume rendered vascular perfusion, OCTA en face images were binarized in order to obtain two-dimensional (2D) perfusion density metrics. Mean ± SD age was 27.2 ± 10.2 years [range 19–64 years] in the diabetic group and 31.0 ± 11.4 years [range 19–61 years] in the control group (p = 0.145). The 3D vascular volume was 0.27 ± 0.05 mm3 in the diabetic group and 0.29 ± 0.04 mm3 in the control group (p = 0.020). The 3D perfusion density was 9.3 ± 1.6% and 10.3 ± 1.6% in diabetic patients and controls, respectively (p = 0.005). Using a 2D visualization, the perfusion density was lower in diabetic patients, but only at the deep vascular complex (DVC) level (38.9 ± 3.7% in diabetes and 41.0 ± 3.1% in controls, p = 0.001), while no differences were detected at the superficial capillary plexus (SCP) level (34.4 ± 3.1% and 34.3 ± 3.8% in the diabetic and healthy subjects, respectively, p = 0.899). In conclusion, eyes without signs of DR of patients with diabetes have a reduced volume rendered macular perfusion compared to control healthy eyes.

PurposeThe 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.MethodsIn 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).ResultsBoth 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.ConclusionIn 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.

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.

PurposePeripheral neuropathy could complicate diabetes mellitus (DM). In vivo confocal microscopy (IVCM) is an ocular examination for the diagnosis of small fiber neuropathies and the detection of the earliest corneal sub-basal nerve plexus (SBP) alterations. Corneal SBP characteristics include focal enlargement along with the nerve fiber, called corneal beadings. These dilatations represent a mitochondrial accumulation induced by the reactive oxygen stress, as a consequence of hyperglycemia. For this reason, corneal beadings are considered indicative of metabolic activity. This study aimed to describe the corneal characteristics of a population of type 1 diabetes mellitus (T1DM) well metabolically controlled, using a new algorithm for the analysis of corneal beading size (BS).MethodsPatients aged ≥18 years affected by T1DM were compared with healthy subjects who underwent IVCM (Confoscan 4; Nidek Technologies Padova, Italy). Starting from the coordinates of the beadings detected by the IVCM, we implemented a new algorithm for automatically measuring BS in corneal SBP images.ResultsWe compared 20 eyes of T1DM patients with 26 healthy controls. The corneal nerves' fiber length (p = 0.008), corneal nerves' fiber length density (p = 0.008), and the number of fibers (p = 0.017) were significantly lower in the diabetic group compared with controls. There was no difference between diabetic and healthy eyes in the mean number of corneal beadings both in the frame of analysis (p = 0.606) and for 0.1 mm of SBP nerve (p = 0.145). Regarding the BS, patients with T1DM had corneal beadings larger than controls (p = 0.036).ConclusionsWe found that the corneal beadings parameters are similar in healthy and T1DM individuals. Nevertheless, measuring the BS with our algorithm, we showed that corneal beadings are enlarged in patients affected by T1DM when compared with healthy controls. Identifying beading expansion in corneal nerve fiber using IVCM should become a useful tool to predict peripheral neuropathy at an early stage.

Abstract Optical coherence tomography angiography (OCTA) has significantly expanded our knowledge of the ocular vasculature. In this review, we provide a discussion of the fundamental principles of OCTA and the application of this imaging modality to study the retinal and choroidal vessels. These guidelines are focused on 2020, and include updates since the 2019 publication. Importantly, we will comment on recent findings on OCTA technology with a special focus on the three-dimensional (3D) OCTA visualization.

Purpose: This study evaluates if the addition of a curcumin formulation with a polyvinylpyrrolidone-hydrophilic carrier (CHC; Diabec®, Alfa Intes, Italy) to intravitreal injections of dexamethasone (DEX-IVT) can affect the morphological retinal characteristics, extending the steroid re-treatment period in patients with diabetic macular edema (DME).Methods: A randomized controlled clinical trial was carried out in DME patients, randomly assigned to receive DEX-IVT or DEX-IVT and a CHC. The evaluation of the mean difference of central retinal thickness (CRT) was the primary aim. Secondary aims were the evaluations of best-corrected visual acuity, differences in the predetermined retinal layer thickness, the number/time of re-treatment, and the assessment of safety.Results: A total of 73 DME patients were included (35 in the control group and 38 in the combined therapy group). In both the control and combined therapy groups, the mean CRT change from T0 to the 6 months’ evaluation was significant (p = 0.00). The mean CRT result was significantly different at month 4 (p = 0.01) between the control and combined therapy groups, with a greater reduction in the combined therapy group, in particular, in patients with ≤10 years of diabetes. A trend of CRT reduction in the combined therapy group has been observed also considering patients with subfoveal neuroretinal detachment. In addition, we observed that the reduction of inner retinal layer thickness was greater in the combination group, in comparison with controls.Conclusion: The combination of a CHC to DEX-IVT is a promising therapeutic option in case of DME, in particular, for patients with early-stage diabetes and with an inflammatory phenotype. Further studies will be necessary to confirm these findings.

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.

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.

PRPH2 gene mutations are frequently found in inherited retinal dystrophies (IRD) and are associated with a wide spectrum of clinical phenotypes. We studied 28 subjects affected by IRD carrying pathogenic PRPH2 mutations, belonging to 11 unrelated families. Functional tests (best-corrected visual acuity measurement, chromatic test, visual field, full-field, 30 Hz flicker, and multifocal electroretinogram), morphological retino-choroidal imaging (optical coherence tomography, optical coherence tomography angiography, and fundus autofluorescence), and clinical data were collected and analyzed. Common primary complaints, with onset in their 40s, were visual acuity reduction and abnormal dark adaptation. Visual acuity ranged from light perception to 20/20 Snellen. Visual field peripheral constriction and central scotoma were found. Chromatic sense was reduced in one third of patients. Electrophysiological tests were abnormal in most of the patients. Choroidal neovascular lesions were detected in five patients. Three novel PRPH2 variants were found in four different families. Based on the present multimodal study, we identified seven distinct PRPH2 phenotypes in 11 unrelated families carrying either different mutations or the same mutation, both within the same family or among them. Fundus autofluorescence modality turned out to be the most adequate imaging method for early recognition of this dystrophy, and the optical coherence tomography angiography was highly informative to promptly detect choroidal neovascularization, even in the presence of the extensive chorioretinal atrophy phenotype.

Carfilzomib is a last generation proteasome inhibitor (PI) with proven clinical efficacy in the treatment of relapsed/refractory multiple myeloma. This drug is considered to be extremely specific in inhibiting the chymotrypsin-like activity of the 20S proteasome, encoded by the β5 subunit, overcoming some bortezomib limitations, the first PI approved for multiple myeloma therapy which is however burdened by a significant toxicity profile, due also to its off-target effects. Here, molecular approaches coupled with molecular docking studies have been used to unveil that the Insulin-Degrading Enzyme, a ubiquitous and highly conserved Zn2+ peptidase, often found to associate with proteasome in cell-based models, is targeted by carfilzomib in vitro. The drug behaves as a modulator of IDE activity, displaying an inhibitory effect over 10-fold lower than for the 20S. Notably, the interaction of IDE with the 20S enhances in vitro the inhibitory power of carfilzomib on proteasome, so that the IDE-20S complex is an even better target of carfilzomib than the 20S alone. Furthermore, IDE gene silencing after delivery of antisense oligonucleotides (siRNA) significantly reduced carfilzomib cytotoxicity in rMC1 cells, a validated model of Muller glia, suggesting that, in cells, the inhibitory activity of this drug on cell proliferation is somewhat linked to IDE and, possibly, also to its interaction with proteasome.

Background: To employ optical coherence tomography angiography (OCTA) to evaluate the effects of hydroxychloroquine (HCQ) on the superficial capillary plexus (SCP) and deep retinal capillary plexus (DCP) in patients affected by rheumatoid arthritis (RA). Methods: Patients with recent diagnosis of “definite RA”, based on 2010 Rheumatoid Arthritis Classification Criteria, were included in a prospective, observational imaging study carried out by the G.B. Bietti Foundation between March 2019 and January 2020. Vessel density (VD) of SCP and DCP, central foveal thickness (CFT) and foveal avascular zone (FAZ) values were collected by OCTA. The primary outcome measure was the VD alteration of SCP and DCP in RA-patients after one year of HCQ treatment. Results: OCTA data analysis showed no statistically significant reduction in the mean VD of SCP and DCP, including the mean global area, central subfield, inner ring and temporal, superior, nasal, and inferior sectors, as well as in the mean CFT and FAZ areas. Conclusions: OCTA demonstrated no early change in the VD in the SCP and DCP, in RA-patients after one year of HCQ treatment. A longer monitoring period would more precisely establish the treatment’s effect on the VD and its correlation with HCQ toxicity.

Abstract Case-control observational study to evaluate the microvascular and macrovascular changes in patients with hypertension secondary to primary aldosteronism (PA), essential hypertension (EH) and healthy subjects. Measurements of arterial stiffness including augmentation index (AIx) and pulse wave velocity (PWV) were assessed using a TensioClinic arteriograph system. Retinal microcirculation was imaged by a Retinal Vessel Analyzer (RVA) and a non-midriatic camera (Topcon-TRC-NV2000). IMEDOS software analyzed the retinal artery diameter (RAD), retinal vein diameters (RVD) and arteriole-to-venule ratio (AVR) of the vessels coming off the optic disc. Thirty, 39 and 35 patients were included in the PA, EH and control group, respectively. The PA group showed higher PWV values compared only with the control group. The mean brachial and aortic AIx values did not show significant difference between groups. In the PA group, the mean RVD and AVR values were significantly lower than in the EH and control groups, whereas the parameters did not differ between the EH and control groups. In conclusion, AVR appears significantly modified in the PA group compared with the EH group and could represent an early and more reliable indicator of microvascular remodeling.

Purpose. To assess retinal sensitivity and retinal morphologic changes of capillary nonperfused areas in diabetic macular ischemia. Methods. Observational cross-sectional study. Patients were examined at IRCCS—Bietti Foundation, Rome, Italy. Fourteen consecutive diabetic eyes showing outer retinal changes on spectral domain optical coherence tomography B-scan were included. Ten eyes of ten diabetic patients with normal outer retinal structure on SD-OCT were included as controls. All eyes underwent optical coherence tomography angiography (OCTA) and MP1 microperimetry. To explore the outer retina findings and localized areas of capillary nonperfusion at the superficial and deep capillary plexus, we used the Spectralis HRA + OCTA (Heidelberg Engineering, Heidelberg, Germany). The B-scans as either normal or having outer retinal disruption and the enface images at the level of the superficial and/or deep capillary plexus were evaluated to identify areas of capillary nonperfusion. Results. Fourteen eyes of 12 consecutive type 2 diabetic patients with outer retinal disruption on SD-OCT showed that areas of capillary nonperfusion of the deep capillary plexus were colocalized to areas of reduced retinal sensitivity. Conclusions. On optical coherence tomography angiography, areas of capillary nonperfusion of deep capillary plexus due to macular ischemia are associated with photoreceptor structural abnormalities and retinal sensitivity loss on microperimetry. This highlights that the health status of deep capillary plexus and not only the choroid is important to the oxygen requirements of the photoreceptors in patients with diabetic macular ischemia. Also, the anatomical and functional consequences of these findings might help to explore the efficacy of new therapy into the macular area in clinical practice.

Purpose. The purpose of our study is to describe the in vivo corneal confocal microscopy characteristics of subbasal nerve plexus in a highly selected population of patients affected by type 1 diabetes mellitus (T1DM) without any microvascular diabetes complications. Methods. We included 19 T1DM patients without diabetic peripheral neuropathy, diabetic autonomic neuropathy, diabetic retinopathy, and microalbuminuria. All patients underwent in vivo corneal confocal microscopy and blood analysis to determine subbasal nerve plexus parameters and their correlation with clinical data. We compared the results with 19 healthy controls. Results. The T1DM group showed a significant decrease of the nerve fiber length (P=0.032), the nerve fiber length density (P=0.034), the number of fibers (P=0.005), and the number of branchings (P=0.028), compared to healthy subjects. The nerve fiber length, nerve fiber length density, and number of fibers were directly related to the age at onset of diabetes and inversely to the duration of DM. BMI (body mass index) was highly related to the nerve fiber length (r = −0.6, P=0.007), to the nerve fiber length density (r = −0.6, P=0.007), and to the number of fibers (r = −0.587, P=0.008). No significant correlations were found between the corneal parameters and HbA1c. Conclusions. Early subclinical fiber corneal variation could be easily detected using in vivo corneal confocal microscopy, even in type 1 diabetes without any microvascular diabetes complications, including diabetic peripheral neuropathy, diabetic autonomic neuropathy, diabetic retinopathy, and microalbuminuria.

Cytidine 5’-diphosphocholine has been widely studied in systemic neurodegenerative diseases, like Alzheimer’s disease, Parkinson’s disease, and brain ischemia. The rationale for the use of citicoline in ophthalmological neurodegenerative diseases, including glaucoma, anterior ischemic optic neuropathy, and diabetic retinopathy, is founded on its multifactorial mechanism of action and the involvement in several metabolic pathways, including phospholipid homeostasis, mitochondrial dynamics, as well as cholinergic and dopaminergic transmission, all being involved in the complexity of the visual transmission. This narrative review is aimed at reporting both pre-clinical data regarding the involvement of citicoline in such metabolic pathways (including new insights about its role in the intracellular proteostasis through an interaction with the proteasome) and its effects on clinical psychophysical, electrophysiological, and morphological outcomes following its use in ophthalmological neurodegenerative diseases (including the results of the most recent prospective randomized clinical trials).

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Central serous chorioretinopathy represents the fourth most frequent retinal disorder, occurring especially in young age. Central serous chorioretinopathy is mainly characterized by macular serous retinal detachment and although the clinical course moves frequently toward a spontaneous resolution, the subretinal fluid may persist for a long time, thus evolving to the chronic form, and leading to a potential damage of the retinal pigment epithelium and to photoreceptors. The photodynamic therapy with verteporfin plays an important role in the armamentarium among the many therapeutic options employed in this complex retinal disorder. In this review, the authors aim to summarize data of efficacy and safety of PDT focusing especially on mechanisms of action of the PDT and providing comparative outcomes with the alternative therapeutic approaches, including especially the subthreshold laser treatment.

Objectives. It has been already confirmed that retinal neurodegeneration has a predictive value in the development of microvascular alterations in diabetic retinopathy. However, no data are available on the association between neuroretinal dysfunction and peripheral motor unit loss. Our study, therefore, was aimed at investigating the hypothesis that retinal neurodegeneration could be considered an early marker of diabetic peripheral neuropathy (DPN). Methods. 20 T1DM patients with no symptoms/signs of peripheral polyneuropathy, without DR or with very mild nonproliferative DR, and 14 healthy controls (C) age- and gender-matched were enrolled. The following electrophysiological tests were performed: standard nerve conduction studies (NCS) and incremental motor unit number estimation (MUNE) from the abductor hallux (AH) and abductor digiti minimi (ADM). Neuroretinal function was studied by multifocal electroretinogram (MfERG) recordings, measuring response amplitude density (RAD) and implicit time (IT) from rings and sectors of superior (S)/inferior (I)/temporal (T)/nasal (N) macular sectors up to 10 degrees of foveal eccentricity. Results. MfERG RADs from rings and sectors were significantly reduced in T1DM (p

Adaptive optics (AO) is a technology used to improve the performance of optical systems by reducing the effects of optical aberrations. The direct visualization of the photoreceptor cells, capillaries and nerve fiber bundles represents the major benefit of adding AO to retinal imaging. Adaptive optics is opening a new frontier for clinical research in ophthalmology, providing new information on the early pathological changes of the retinal microstructures in various retinal diseases. We have reviewed AO technology for retinal imaging, providing information on the core components of an AO retinal camera. The most commonly used wavefront sensing and correcting elements are discussed. Furthermore, we discuss current applications of AO imaging to a population of healthy adults and to the most frequent causes of blindness, including diabetic retinopathy, age-related macular degeneration and glaucoma. We conclude our work with a discussion on future clinical prospects for AO retinal imaging.

PURPOSE:To investigate a set of adaptive optics (AO) imaging biomarkers for the assessment of changes of the cone mosaic spatial arrangement in patients with type 1 diabetes mellitus (DM1). METHODS:16 patients with ≥20/20 visual acuity and a diagnosis of DM1 in the past 8 years to 37 years and 20 age-matched healthy volunteers were recruited in this study. Cone density, cone spacing and Voronoi diagrams were calculated on 160x160 μm images of the cone mosaic acquired with an AO flood illumination retinal camera at 1.5 degrees eccentricity from the fovea along all retinal meridians. From the cone spacing measures and Voronoi diagrams, the linear dispersion index (LDi) and the heterogeneity packing index (HPi) were computed respectively. Logistic regression analysis was conducted to discriminate DM1 patients without diabetic retinopathy from controls using the cone metrics as predictors. RESULTS:Of the 16 DM1 patients, eight had no signs of diabetic retinopathy (noDR) and eight had mild nonproliferative diabetic retinopathy (NPDR) on fundoscopy. On average, cone density, LDi and HPi values were significantly different (P