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Abstract Introduction Despite an improved understanding of its pathogenesis, dry eye disease (DED) remains relatively underestimated and its treatment challenging. A better alignment between the clinical evaluation and the patient self-assessment also requires capturing the whole patient experience of DED. This project aimed to unveil this experience through narrative medicine (NM). Methods The project involved 38 expert centres in Italy and one in San Marino, targeting adult patients with DED, their informal caregivers and their treating ophthalmologists. Written narratives and sociodemographic and quality of life (QoL)-related data were anonymously collected through the project’s webpage. Narratives were analysed through MAXQDA (VERBI Software, Berlin, Germany), NM classifications and content analysis. Results A total of 171 patients with DED, 37 informal caregivers and 81 ophthalmologists participated in the research. DED was defined as a disabling condition by 19% of patients and 35% of caregivers; 70% of patients reported that a therapeutic alliance is an integral part of DED treatment and 32% hope for more effective therapies. Forty-four per cent of patients assessed their own QoL as good; however, DED emerged as importantly impacting work performance and social events. DED physical, emotional and economic burden and the cruciality of a trusting care relationship represent the main themes that emerged across all narratives, while empathy and effective treatment are among the factors favouring coping with DED. Conclusion This project marked a pioneering initiative investigating the lived experience of patients with DED through NM, simultaneously involving all viewpoints involved in the care pathway. NM enabled the unveiling of factors favouring the ability to cope with DED and its associated QoL implications and provided valuable insights to improve the therapeutic alliance.

Abstract There is a lack of knowledge about the effect of flavanols-rich dark chocolate intake on the anatomy and functionality of retinal vessels. The aim of this study prospective, randomized, blind, crossover clinical trial (ClinicalTrials.gov Identifier: NCT05227248, 07/02/2022) was to evaluate the effect of dark-chocolate intake on the functionality and anatomy of the retinal vessels in healthy subjects using dynamic vessel analyzer (DVA) and optical coherence tomography angiography (OCT-A). Twenty eyes of 20 healthy subjects (mean age, 24.4 ± 1.6 years; 12 females) were enrolled. Participants were randomized to consume 20 g of dark chocolate or 7.5 g of milk chocolate. Visual function, DVA and OCT-A parameters were evaluated before chocolate consumption and two hours later. One week later, the same participants were tested before and after consuming the opposite chocolate. Using OCT-A, no differences were disclosed in terms of perfusion density changes after dark-chocolate and milk-chocolate intake analyzing all chorioretinal plexuses (p > 0.09 in all analyses). Using DVA, a significant increase in the arterial dilation percentage after flicker stimulation was disclosed comparing baseline (2.750 ± 2.054%) with values after the dark chocolate intake (4.145 ± 3.055%, p = 0.016). This difference was not disclosed after the milk chocolate intake (p = 0.465). We disclosed that a reasonable amount of flavanols-rich chocolate in healthy subjects has benefic functional short-term effects in retinal vessels measured with DVA. This suggests a potential role of dark chocolate intake on retinal vessels. Further studies with long-term follow-up are warranted to show if the chronic assumption of dark chocolate could play a favorable role in the prevention of retinal diseases.

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 The aim of this work is to estimate the sensitivity, specificity, and misclassification rate of an automated retinal image analysis system (ARIAS) in diagnosing active diabetic macular edema (DME) and to identify factors associated with true and false positives. Methods We conducted a cross-sectional study of prospectively enrolled patients with diabetes mellitus (DM) referred to a tertiary medical retina center for screening or management of DME. All patients underwent two-field fundus photography (macula- and disc-centered) with a true-color confocal camera; images were processed by EyeArt V.2.1.0 (Woodland Hills, CA, USA). Active DME was defined as the presence of intraretinal or subretinal fluid on spectral-domain optical coherence tomography (SD-OCT). Sensitivity and specificity and their 95% confidence intervals (CIs) were calculated. Variables associated with true (i.e., DME labeled as present by ARIAS + fluid on SD-OCT) and false positives (i.e., DME labeled as present by ARIAS + no fluid on SD-OCT) of active DME were explored. Results A total of 298 eyes were included; 92 eyes (31%) had active DME. ARIAS sensitivity and specificity were 82.61% (95% CI 72.37–89.60) and 84.47% (95% CI 78.34–89.10). The misclassification rate was 16%. Factors associated with true positives included younger age (p = 0.01), shorter DM duration (p = 0.006), presence of hard exudates (p = 0.005), and microaneurysms (p = 0.002). Factors associated with false positives included longer DM duration (p = 0.01), worse diabetic retinopathy severity (p = 0.008), history of inactivated DME (p

Abstract Introduction Macular neovascularization (MNV) secondary to age-related macular degeneration (AMD) is well managed by anti-vascular endothelial growth factor (anti-VEGF) intravitreal injections. However, outer retinal atrophy represents an unavoidable occurrence detected during follow-up. Several imaging metrics have been proposed as clinically relevant in stratifying the risk of onset of outer retinal atrophy. The main goal of this study is to evaluate the impact of noninvasive imaging metrics on the assessment of outer retinal atrophy onset in a large cohort of eyes with neovascular AMD managed in a real-world setting. Methods This study was a prospective, observational, case series. We included patients affected by newly diagnosed neovascular AMD, requiring anti-VEGF intravitreal injections. We collected clinical and imaging data, with a planned follow-up of 24 months. The multimodal imaging protocol included optical coherence tomography, optical coherence tomography angiography, and fundus autofluorescence. We collected noninvasive imaging metrics and we assessed the relationship with the morphological and functional outcome evaluated at 12-month and 24-month time points. Results We included 370 eyes of 370 patients with exudative AMD (210 male; mean age 79 ± 8 years). MNV were classified as follows: type 1, 198 (54%); type 2, 89 (24%); polypoidal choroidal vasculopathy, 29 (7%); and type 3, 54 (15%). A total of 120 out of 370 eyes (33%) showed complete outer retinal atrophy at the end of the 2-year follow-up. The presence of intraretinal fluid, thinning of the Sattler choroidal layer, late anti-VEGF switch, the overall number of anti-VEGF injections, and the perfusion characteristics of the MNV were found to be the most relevant factors associated with the onset of outer retinal atrophy. The other collected metrics were found to be less clinically relevant, also showing no cumulative effect in the multivariate analysis (p > 0.05). Conclusions We identified imaging metrics significantly associated with the 2-year risk onset of outer retinal atrophy. These metrics might pave the way for the development of future customized anti-VEGF treatment strategies.

Abstract Introduction This study assessed the European School of Advanced Studies in Ophthalmology (ESASO) classification’s prognostic value for diabetic macular edema (DME) in predicting intravitreal therapy outcomes. Methods In this retrospective, multicenter study, patients aged > 50 years with type 1 or 2 diabetes and DME received intravitreal antivascular endothelial growth factor (anti-VEGF) agents (ranibizumab, bevacizumab, and aflibercept) or steroids (dexamethasone). The primary outcome was visual acuity (VA) change post-treatment, termed as functional response, measured 4–6 weeks post-third anti-VEGF or 12–16 weeks post-steroid injection, stratified by initial DME stage. Results Of the 560 eyes studied (62% male, mean age 66.7 years), 31% were classified as stage 1 (early), 50% stage 2 (advanced), 17% stage 3 (severe), and 2% stage 4 (atrophic). Visual acuity (VA; decimal) improved by 0.12–0.15 decimals in stages 1–2 but only 0.03 decimal in stage 3 (all p

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

Purpose: To report a case of multifocal vitelliform lesions in a patient affected by metabolic encephalomyopathy, lactic acidosis and stroke-like episodes (MELAS) with the m.3243A>G variant. Observations: A 37-year-old woman affected by MELAS was referred to our center for progressive vision deterioration. On fundus examination, she presented bilateral macular atrophy associated in the left eye with neurosensory detachment, along with several bilateral vitelliform lesions close to the vascular arcades. We describe the dynamic evolution of the vitelliform lesions, which could either enlarge and coalesce or undergo atrophic evolution. Conclusions: Mitochondrial retinopathy due to the m.3243A>G variant can be associated with multifocal vitelliform lesions.

Purpose: To report a challenging case of corneal descemetocele following Nd:YAG laser capsulotomy for posterior capsule opacification in a patient with Steven Johnson syndrome (SJS). Observations: A single-eye 52 year-old man, with a history of Steven Johnson syndrome, presented with severe eye pain and profound vision reduction in his left eye two days after undergoing Nd:YAG laser capsulotomy using the standard Abraham contact lens. A corneal descemetocele was identified and subsequently confirmed by anterior segment optical coherence tomography. He was promptly treated with the application of a therapeutic contact lens and sustained antibiotic regimen (preservative-free fluoroquinolone drops every 4 hours for 6 weeks) until healing of the corneal epithelium. Throughout the following eight weeks AS-OCT showed favorable anatomical and functional outcomes, achieving a substantial spontaneous healing. Conclusions and Importance: Corneal descemetocele may occur after Nd:YAG laser capsulotomy in patients with Steven Johnson syndrome. This case strengthens the critical importance of a careful preoperative assessment and meticulous postoperative management in high-risk patients, such as those with Steven Johnson syndrome, even after seemingly routine and safe ophthalmic procedures.

Purpose: To describe a case of bilateral panuveitis in a patient with Stimulator of Interferon Genes (STING)-Associated Vasculitis with Onset in Infancy (SAVI). Observations: A 45-year-old patient diagnosed with SAVI presented bilateral panuveitis and uncontrolled secondary intraocular hypertension due to structural complications from uveitis. Multimodal imaging revealed the presence of intraretinal fluid and bilateral vasculitis. The patient was started with systemic methotrexate. Conclusions and importance: This case is essential to characterize ocular involvement in patients with SAVI. Awareness of these ocular manifestations is crucial for timely management and improvement of visual prognosis.

Abstract Geographic atrophy is an eye disease that greatly interferes with the daily lives of patients and their families, posing a serious threat to the aging European demographic. Over the past 30 months, this initiative has assembled leading experts in the field of ophthalmology to share insights on the necessary policy steps that need to be taken to overcome this challenge on an EU-wide scale. Through analyzing best practices in Germany, Italy, France, and Spain, this consensus paper sets out a series of policy recommendations, which, if implemented, could greatly benefit all individuals affected by geographic atrophy. Amongst other features, these countries have provided valuable examples of awareness campaigns and an overall commitment to inclusive and comprehensive policies. The policy recommendations emerging from this paper include the adoption of comprehensive screening programs, retinal disease screening in the EU Driving License Directive, the development of a white paper at the European Commission, and the creation of Council recommendations on eye health screening. Given the significant improvements made at the national level throughout the EU, countries will require unitary support at the European level to further develop their policies and successfully address the burden of geographic atrophy.

Abstract Optical coherence tomography angiography (OCTA) has extensively enhanced our comprehension of eye microcirculation and of its associated diseases. In this narrative review, we explored the key concepts behind OCTA, as well as the most recent evidence in the pathophysiology of age-related macular degeneration (AMD) made possible by OCTA. These recommendations were updated since the publication in 2020, and are targeted for 2023. Importantly, as a future perspective in OCTA technology, we will discuss how artificial intelligence has been applied to OCTA, with a particular emphasis on its application to AMD study.

Abstract Purpose To report eplerenone use by retina specialists worldwide for central serous chorioretinopathy (CSCR). Methods A self-reporting questionnaire was distributed to retina specialists worldwide to gather clinicians’ perspectives on CSCR cases treated, eplerenone dosage and duration, reasons to use it, and side effects. Results The survey included 241 retina specialists (122 Indian and 119 international) with an average experience of 15.69 ± 9.59 years. Oral eplerenone was used to treat CSCR by 149 (62%) participants. Only 6% (n = 9) had easy access to verteporfin dye and photodynamic therapy. 30 (20%) of the 149 respondents changed their treatment with eplerenone after VICI trial results. Eplerenone was prescribed mostly for chronic CSCR (n = 86, 58%), regardless of involvement laterality. 62% (n = 92) had fewer than 25% CSCR cases treated with eplerenone. 85 (57%) respondents used eplerenone only when other treatments failed, while 36 (24%) used it as first-line treatment. 73 (49%) respondents, prescribed eplerenone at a 50 mg daily dose and 137 (92%) retina specialists used eplerenone for 0–3 months. The drug’s efficacy dissatisfied 21 (14%) study participants. 124 (83%) study participants did not encounter any ocular or systemic side effects with eplerenone use. Eplerenone related kidney and electrolyte issues were noted by 11 (7%) study participants. Conclusion The treatment of CSCR varies around the world and is primarily influenced by the photodynamic therapy availability and the findings of VICI trial. Despite the limited benefit of eplerenone reported by the VICI trial, it is still used as evidenced by real-world experience. Trial Registration Number Not applicable.

Abstract Background Photobiomodulation (PBM) relies on the pathophysiological mechanism whereby red to near-infrared light can target mitochondrial activity and promote ATP synthesis. Preclinical and clinical studies have shown promising results in treating intermediate age-related macular degeneration (AMD), since PBM can produce photochemical reactions in endogenous retinal chromophores. Currently, PBM is approved by the Food and Drug Administration and by the European Medicines Agency for the treatment of intermediate AMD. This narrative review aimed to evaluate the available evidence on the effectiveness and safety of PBM in treating intermediate AMD. Methods A comprehensive search was conducted using the PubMed database, employing the keywords “photobiomodulation” and “age-related macular degeneration.” All English-language studies published up to June 2023 were reviewed, and the search was expanded to include relevant references from selected articles. The included publications were analyzed for this review. Results The available studies on PBM in AMD demonstrated promising but inconsistent results. PBM showed potential in improving best-corrected visual acuity (BCVA) and contrast sensitivity (CS) in patients with AMD. Some studies also suggested a reduction in AMD lesions, such as drusen volume. However, the long-term efficacy and optimal treatment parameters of PBM in AMD remained to be fully determined due to the limitations of the available studies. These included variations in irradiation techniques, wavelengths, exposure times, and treatment sessions, making it challenging to generalize the effectiveness of PBM. Furthermore, the lack of accurate classification of AMD phenotypes in the available studies hindered the understanding of which phenotypes could truly benefit from this treatment. Finally, the strength of evidence varied among studies, with limited sample sizes, unpublished results, and only three randomized sham-controlled trials. Conclusions Currently, the effectiveness of PBM in promoting drusen resorption or preventing progression to advanced forms of AMD, as observed in the cited studies, remains uncertain.

Abstract Introduction This study investigates factors associated with recurrent rhegmatogenous retinal detachment (RRD), macular complications, and visual outcomes after pars plana vitrectomy (PPV) without perfluorocarbon liquids (PFCLs) for primary RRD. Methods A longitudinal cohort study included consecutive patients with RRD who underwent PFCL-free PPV. Postoperative visual acuity and spectral-domain optical coherence tomography findings [cystoid macular edema (CME), epiretinal membrane (ERM), ellipsoid zone/interdigitation zone (EZ/IZ) damage] were collected. Logistic regression and linear mixed models analyzed rates and risk factors for RRD recurrence, CME, ERM, EZ/IZ damage, and visual acuity at 12 months. Results 346 eyes with RRD were studied. Single-operation success rates were 96% and 93% for uncomplicated (n = 274 eyes) and complicated (n = 72 eyes) RRD, respectively. Factors associated with RRD recurrence were posterior retinal breaks [odds ratio (OR) = 10.7 compared to peripheral retinal breaks, p = 0.008], silicone oil tamponade (OR = 5.66 compared to gas, p = 0.01), and sectorial laser retinopexy (OR = 4.34 compared to 360° laser retinopexy, p = 0.007). The prevalence of CME, ERM, and EZ/IZ damage at 12 months was 10%, 9%, and 6%, respectively. Eyes with EZ/IZ defects had worse postoperative visual acuity in both uncomplicated and complicated RRD. Proliferative vitreoretinopathy (OR = 2.95, p = 0.03) and silicone oil tamponade (OR = 3.70 compared to gas, p = 0.05) were associated with EZ/IZ damage. Conclusions PFCL-free PPV demonstrated satisfactory single-operation success rates for uncomplicated and complicated RRD, with a low prevalence of macular complications. Analyzing factors associated with RRD recurrence can provide provisional recommendations for PFCL-free approaches in the absence of randomized trials.

Background and objectives: Age-related macular degeneration (AMD) is a complex and multifactorial condition that can lead to permanent vision loss once it progresses to the neovascular exudative stage. This review aims to summarize the use of deep learning in neovascular AMD. Materials and Methods: Pubmed search. Results: Deep learning has demonstrated effectiveness in analyzing structural OCT images in patients with neovascular AMD. This review outlines the role of deep learning in identifying and measuring biomarkers linked to an elevated risk of transitioning to the neovascular form of AMD. Additionally, deep learning techniques can quantify critical OCT features associated with neovascular AMD, which have prognostic implications for these patients. Incorporating deep learning into the assessment of neovascular AMD eyes holds promise for enhancing clinical management strategies for affected individuals. Conclusion: Several studies have demonstrated effectiveness of deep learning in assessing neovascular AMD patients and this has a promising role in the assessment of these patients.

Abstract Introduction To describe subclinical angioid streaks (AS) as a frequent, peculiar age-related macular degeneration (AMD) phenotype, comparing features of eyes with subclinical AS with those of eyes with AMD without AS. Methods This was a retrospective, observational study. Among a patient cohort with AMD, we selected patients without known causes for AS whose eyes showed signs of angioid streaks (AS) on structural optical coherence tomography (OCT) but not on fundus examination. Selected OCT features of AS were Bruch’s membrane (BM) breaks and large BM dehiscences. Results Among 543 eyes of 274 patients with AMD (mean ± standard deviation: 82 ± 7 years), 73 eyes of 46 patients (81 ± 7 years; p = 0.432) showed AS features on OCT (OCT AS) that were not visible on fundus examination. Estimated prevalence of subclinical age-related AS was 13.4% (95% confidence interval 10.3–16.3%) in this AMD population. Fifty-three eyes (73%) with AS features were affected by peripapillary atrophy, often with a “petaloid-like” pattern, similar to typical features of AS disease. Almost all cases (97%) presented reticular pseudodrusen (RPD), with (41%) or without (59%) drusen showing a significant difference in RPD prevalence in OCT AS eyes in comparison to AMD eyes without subclinical AS using generalized estimating equations (P

Abstract Introduction Foveal eversion (FE) is a recently described optical coherence tomography (OCT) finding associated with negative outcome in diabetic macular edema. The main goal of the present study was to investigate the role of the FE metric in the diagnostic workup of retinal vein occlusion (RVO). Methods This study was a retrospective, observational case series. We included 168 eyes (168 patients) affected by central RVO (CRVO) and 116 eyes (116 patients) affected by branch (RVO). We collected clinical and imaging data from CRVO and BRVO eyes affected by macular edema with a minimum follow-up of 12 months. On structural OCT, we classified FE as pattern 1a, characterized by thick vertical intraretinal columns, pattern 1b, presenting thin vertical intraretinal lines, and pattern 2, showing no signs of vertical lines in the context of the cystoid macular edema. For statistical purposes, we considered data collected at baseline, after 1 year and at the last follow-up. Results The mean follow-up was 40 ± 25 months for CRVO eyes and 36 ± 24 months for BRVO eyes. We found FE in 64 of 168 CRVO eyes (38%) and in 25 of 116 BRVO eyes (22%). Most of the eyes developed FE during the follow-up. For CRVO eyes, we found 6 eyes (9%) with pattern 1a, 17 eyes (26%) with pattern 1b and 41 eyes (65%) with pattern 2. Of those BRVO eyes with FE, we found 8 eyes (32%) with pattern 1a + 1b and 17 eyes (68%) with pattern 2. In both CRVO and BRVO the presence of FE was significantly associated with higher persistence of macular edema and worse outcome, with FE pattern 2 representing the most severe condition. Remarkably, FE patterns 1a and 1b were characterized by BCVA stability over the follow-up, whereas FE pattern 2 showed significant bestcorrected visual acuity (BCVA) worsening at the end of the follow-up. Conclusions FE can be considered a negative prognostic biomarker in RVO, associated with higher persistence of macular edema and worse visual outcome. Müller cell impairment might represent the pathogenic mechanism leading to the loss of macular structural support and impairment of fluid homeostasis.

Abstract Introduction This study aimed to describe the effects of no-dose full-fluence photodynamic therapy without verteporfin (no-dose PDT) and to compare no-dose PDT with half-dose verteporfin full-fluence photodynamic therapy (HDFF PDT) for managing chronic central serous chorioretinopathy (cCSC). Methods This retrospective study evaluated 11 patients with chronic recurrent CSC treated with no-dose PDT between January 2019 and March 2022. Most of these patients were also treated with HDFF PDT a minimum of 3 months before and were considered as the control group. We described the changes of best corrected visual acuity (BCVA), maximum subretinal fluid (mSRF), foveal subretinal fluid (fSRF), and choroidal thickness (CT) 8 ± 2 weeks after no-dose PDT, and we compared BVCA, mSRF, fSRF, and CT of no-dose PDT with those of the of same patients previously treated with HDFF PDT. Results Fifteen eyes of 11 patients (10 male, mean age 54 ± 12 years) received no-dose PDT; among these, 10 eyes of 8 patients (7 male, mean age 53 ± 12 years) also received HDFF PDT. Three eyes showed complete resolution of fSRF after no-dose PDT. No significant differences were disclosed between treatment with and without verteporfin comparing BCVA, mSRF, fSRF, and CT at baseline and 8 ± 2 weeks from the treatment (p > 0.05 in all analyses). Conclusion BVCA and CT significantly improved after no-dose PDT. Short-term functional and anatomical treatment outcomes for cCSC were similar for HDFF PDT and no-dose PDT. We hypothesize that the potential benefits of no-dose PDT may arise from thermal elevation that triggers and enhances photochemical activities by endogenous fluorophores, activating a biochemical cascade response that rescues/replaces sick, dysfunctional retinal pigment epithelial (RPE) cells. Results of this study suggest the potential value of a prospective clinical trial to evaluate no-dose PDT for managing cCSC, especially when verteporfin is contraindicated or unavailable.

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.

Purpose: To analyze fixation location and stability in best vitelliform macular dystrophy (BVMD) and test their association with best-corrected visual acuity (BCVA). Design: Observational, cross-sectional study. Participants: Thirty patients (55 eyes) affected by genetically confirmed BVMD were followed up at the Retinal Heredodystrophies Unit of IRCCS San Raffaele Scientific Institute, Milan. Methods: Patients underwent testing with macular integrity assessment (MAIA) microperimeter. Fixation location was measured as distance in degrees (°) between preferred retinal locus (PRL) and estimated fovea location (EFL); fixation was defined as eccentric when the distance between PRL and EFL exceeded 2°. Fixation stability was graded as stable, relatively unstable, or unstable and expressed as bivariate contour ellipse area (BCEA, °2). Main Outcome Measures: Fixation location and stability. Results: The median distance of the PRL from the anatomic fovea was 0.7°, and fixation location was eccentric in 27% of eyes. Fixation was graded as stable in 64% of eyes, relatively unstable in 13%, and unstable in 24%, with a median 95% BCEA of 6.2°2. The atrophic/fibrotic stage was associated with worse fixation parameters (all P

Abstract Introduction In current clinical practice, several optical coherence tomography (OCT) biomarkers have been proposed for the assessment of severity and prognosis of different retinal diseases. Subretinal pseudocysts are subretinal cystoid spaces with hyperreflective borders and only a few single cases have been reported thus far. The aim of the study was to characterize and investigate this novel OCT finding, exploring its clinical outcome. Methods Patients were evaluated retrospectively across different centers. The inclusion criterion was the presence of subretinal cystoid space on OCT scans, regardless of concurrent retinal diseases. Baseline examination was set as the first time the subretinal pseudocyst was identified by OCT. Medical and ophthalmological histories were collected at baseline. OCT and OCT-angiography were performed at baseline and at each follow-up examination. Results Twenty-eight eyes were included in the study and 31 subretinal pseudocysts were characterized. Out of 28 eyes, 16 were diagnosed with neovascular age-related macular degeneration (AMD), 7 with central serous chorioretinopathy, 4 with diabetic retinopathy, and 1 with angioid streaks. Subretinal and intraretinal fluid were present in 25 and 13 eyes, respectively. Mean distance of the subretinal pseudocyst from the fovea was 686 µm. The diameter of the pseudocyst was positively associated with the height of the subretinal fluid (r = 0.46; p = 0.018) and central macular thickness (r = 0.612; p = 0.001). At follow-up, subretinal pseudocysts disappeared in most of the reimaged eyes (16 out of 17). Of these, two patients presented retinal atrophy at baseline examination and eight patients (47%) developed retinal atrophy at follow-up. Conversely, seven eyes (41%) did not develop retinal atrophy. Conclusion Subretinal pseudocysts are precarious OCT findings, usually disclosed in a context of subretinal fluid, and are probably transient alterations within the photoreceptor outer segments and retinal pigment epithelium (RPE) layer. Despite their nature, subretinal pseudocysts have been associated with photoreceptor loss and incomplete RPE definition.

Abstract The aim of this study was to study the retinal vessels in patients affected by vasculogenic erectile dysfunction (ED), using dynamic vessel analyzer (DVA). Patients with vasculogenic ED and control subjects were prospectively enrolled to undergo a complete urological and ophthalmologic evaluation, including DVA and structural optical coherence tomography (OCT). The main outcome measures were: (1) arterial dilation; (2) arterial constriction; (3) reaction amplitude (the difference between arterial dilation and constriction); and, (4) venous dilation. Thirty-five patients with ED and 30 male controls were included in the analysis. Mean ± SD age was 52.0 ± 10.8 years in the ED group and 48.1 ± 16.3 years in the control group (p = 0.317). In the dynamic analysis, the arterial dilation was lower in the ED group (1.88 ± 1.50%), as compared with the control group (3.70 ± 1.56%, p

Abstract The aim of this study was to assess the relationship of clinical characteristics to the rate of retinal thinning in eyes with diabetic macular edema (DME) treated with anti-vascular endothelial growth factor (VEGF) therapy. We analyzed subjects with a long-term follow-up (≥ 3 years) and evidence of resolved DME after the initiation of anti-VEGF therapy (baseline visit). To measure the long-term rate of retinal thinning during treatment, a second visit (first visit with evidence of resolved DME after 3 years) was also considered. A longitudinal quantitative topographical assessment of the inner and outer retinal thicknesses was provided. Clinical characteristics were associated with the rate of longitudinal retinal thinning. We included 56 eyes (50 patients) in the analysis. A significant longitudinal thinning in the inner and outer retina was detected in all the analyzed regions (p values between 0.027 and

Abstract To compare clinical and imaging characteristics of extensive macular atrophy with pseudodrusen-like appearance (EMAP) versus diffuse-trickling geographic atrophy (DTGA) and non-diffuse-trickling geographic atrophy (nDTGA) phenotypes of age-related macular degeneration. Prospective, observational study performed in the Ophthalmology Department of IRCCS San Raffaele Hospital between January 2015 and January 2021. Patients examination included fundus autofluorescence (FAF) and optical coherence tomography at baseline and follow-up visits. We measured subfoveal choroidal thickness (SCT), Sattler/choroid ratio (SCR), choroidal vascularity index and ellipsoid zone disruption distance on OCT scans. We calculated progression rates and circularity of the atrophic lesions on FAF images. These variables were compared between the three groups and correlations with progression rates and visual acuity were assessed. Sixty-three eyes from 63 patients were included: 18 with EMAP, 18 with DTGA and 27 with nDTGA. Mean follow-up was 3.73 ± 2.12 years. EMAP and DTGA shared a faster progression, lower circularity and SCR, and higher EZ disruption distance than nDTGA, while SCT and CVI were similar between the three groups. Baseline circularity and SCR correlated with progression rates. EMAP and DTGA show similar OCT and FAF characteristics, which differ from nDTGA.

Abstract The aim of the study was to characterize macular edema (ME) in retinitis pigmentosa (RP) by means of quantitative optical coherence tomography (OCT)-based imaging. The study was designed as observational, prospective case series, with 1-year follow-up. All RP patients underwent complete ophthalmologic assessment, including structural OCT, OCT angiography, and microperimetry (MP). The primary outcome was the characterization through quantitative OCT-based imaging of RP eyes complicated by ME. A total of 68 RP patients’ eyes (68 patients) and 68 eyes of 68 healthy controls were recruited. Mean BCVA was 0.14 ± 0.17 LogMAR at baseline and 0.18 ± 0.23 LogMAR at 1-year follow-up (p > 0.05). Thirty-four eyes (17 patients; 25%) showed ME, with a mean ME duration of 8 ± 2 months. Most of the eyes were characterized by recurrent ME. The ME was mainly localized in the inner nuclear layer in all eyes. LogMAR BCVA was similar in all RP eyes, whether with or without ME, although those with ME were associated with higher vessel density values, as well as thicker choroidal layers, than those without ME. In conclusion, the inner retina is closely involved in the pathogenesis of ME. The impairment of retinal-choroidal exchanges and Müller cell disruption might be a major pathogenic factor leading to the onset of ME in RP.

Diabetic retinopathy (DR) is the most common microangiopathic complication of diabetes mellitus, representing a major cause of visual impairment in developed countries. Proliferative DR (PDR) represents the last stage of this extremely complex retinal disease, characterized by the development of neovascularization induced by the abnormal production and release of vascular endothelial growth factor (VEGF). The term VEGF includes different isoforms; VEGF-A represents one of the most important pathogenic factors of DR. Anti-VEGF intravitreal therapies radically changed the outcome of DR, due to combined anti-angiogenic and anti-edematous activities. Nowadays, several anti-VEGF molecules exist, characterized by different pharmacological features and duration. With respect to PDR, although anti-VEGF treatments represented a fundamental step forward in the management of this dramatic complication, a big debate is present in the literature regarding the role of anti-VEGF as substitute of panretinal photocoagulation or if these two approaches may be used in combination. In the present review, we provided an update on VEGF isoforms and their role in DR pathogenesis, on current anti-VEGF molecules and emerging new drugs, and on the current management strategies of PDR. There is an overall agreement regarding the relative advantage provided by anti-VEGF, especially looking at the management of PDR patients requiring vitrectomy, with respect to laser. Based on the current data, laser approaches might be avoided when a perfectly planned anti-VEGF therapeutic strategy can be adopted. Conversely, laser treatment may have a role for those patients unable to guarantee enough compliance to anti-VEGF injections.Key messagesVEGF increased production, stimulated by retinal hypoperfusion and ischaemia, is a major pathogenic factor of neovascular complication onset in diabetic retinopathy and of DR stages progression.Nowadays, several anti-VEGF molecules are available in clinical practice and other molecules are currently under investigation. Each anti-VEGF molecule is characterized by different targets and may interact with multiple biochemical pathways within the eye.All the data agreed in considering anti-VEGF molecules as a first line choice for the management of diabetic retinopathy. Laser treatments may have a role in selected advanced cases and for those patients unable to guarantee enough compliance to intravitreal treatments schemes.

Objective: The aim of the current review is to summarize the available evidence to aid clinicians in the surveillance, treatment and follow-up of the different primary tumors developed by patients diagnosed with von Hippel-Lindau (VHL) syndrome. Methods: A non-systematic narrative review of original articles, meta-analyses, and randomized trials was conducted, including articles in the pre-clinical setting to support relevant findings. Results: VHL disease is the most common rare hereditary disorder associated with clear cell renal cell carcinoma. Affected individuals inherit a germline mutation in one VHL allele, and any somatic event that disrupt the other allele can trigger mutations, chromosomal rearrangements, or epigenetic regulations leading to oncogenesis. From a clinical perspective, patients continuously develop multiple primary tumors. Conclusion: Because VHL is considered a rare disease, very limited evidence is available for diagnosis, surveillance, active treatment with local or systemic therapy and follow-up.

Purpose: To identify the vascular biomarkers of peripheral capillary nonperfusion in patients affected by naive central retinal vein occlusion (CRVO), and to analyze their changes over the follow-up. Study Design: Consecutive prospective case series with a planned follow-up of 2 years. Participants: Thirty-five patients affected by CRVO and 35 healthy gender- and age-matched subjects were enrolled in the study. Methods: Ophthalmic examination included best corrected visual acuity (BCVA), ultrawidefield fluorescein angiography (UWFFA), OCT, and OCT angiography (OCTA). Main Outcome Measures: Vessel density (VD) at the superficial capillary plexus and deep capillary plexus (DCP) were calculated on OCTA images. The ischemic index (ISI) was calculated on UWFFA. Results: The mean baseline ISI was 37%, increasing to 40% at the end of the follow-up, whereas it was 4.9% in the patients’ fellow eyes and 4.5% in the control group with no change over the follow-up. OCT angiography revealed VD reduction in the DCP, considering both 3 × 3 mm and 12 × 12 mm scans. The correlation analyses revealed that DCP VD was the only parameter showing a statistically significant correlation with the foveal avascular zone (FAZ) area, BCVA, and ISI. Conclusions: Deep capillary plexus VD impairment is detectable in all CRVO cases, variably involving both the central retina (with enlarged FAZ) and the periphery (with VD reduction in the peripheral retina). The severity of DCP VD reduction has correlates with various clinical markers. Deep capillary plexus VD may represent a crucial biomarker to characterize CRVO, and further studies are necessary to identify the cutoff thresholds for the different clinical manifestations. Financial Disclosure(s): Proprietary or commercial disclosure may be found after the references.

Abstract The aim of the present study was to describe foveal eversion patterns in diabetic macular edema (DME) and to assess their relationship with the course of the disease and the outcome. The study was designed as prospective, observational, with two years of follow-up. DME patients were divided in two groups, one treated by combined anti-VEGF injections and dexamethasone (DEX) implants, and the other treated by fluocinolone acetonide (FAc) implant with additional anti-VEGF retreatments if needed. Main outcome measures were foveal eversion prevalence, foveal eversion patterns, best-corrected visual acuity (BCVA), central macular thickness (CMT), structural OCT metrics, number of intravitreal injections. One hundred and forty-six eyes (146 patients; 80 males; mean age 67 ± 8 years) affected by already treated DME, with 84 eyes treated with anti-VEGF/DEX treatments (mean of 10 ± 3 injections) and 62 treated with FAc implant. Looking at the treatments administered before the inclusion into the study, 84 eyes (58%) were treated with anti-VEGF injections, whereas 62 eyes (42%) underwent a combination of anti-VEGF and corticosteroids implants. DME eyes showed statistically significant improvements of LogMAR BCVA and CMT over the 2-year follow-up. Foveal eversion was found in 83 eyes (57%), categorized as follows: Pattern 1a (16;19%); Pattern 1b (22;27%) and Pattern 2 (45;54%). BCVA improvement was detected in all the subgroups, excepting for Pattern 2, which showed also significantly worse structural OCT parameters. Pattern 1b and Pattern 2 were characterized by significantly higher prevalence of persistent DME (64% and 89% of cases, respectively). Foveal eversion patterns were correlated with progressively worse DME outcome. Foveal eversion may be associated to the loss of foveal homeostasis, with consequent poor response to intravitreal treatments and worse DME outcome.

Background: Leber congenital amaurosis is the first form of inherited retinal dystrophy (IRD) treated with a gene therapy approach using voretigene neparvovec (VN). To date, 42 patients have been treated, 25 of whom, treated at Clinica Oculistica Vanvitelli (Naples), have shown – after 45 days of treatment – a significant increase in dim-light visual function, a widening of the visual field, and an increase in central visual acuity. Objective: A workshop has been organized to foster rapid access, investigate the current organizational scenario, and identify a value framework suitable for making gene therapy delivery efficient in terms of efficacy, safety, and sustainability. Methods: The workshop involved 14 experts in clinical genetics, ophthalmology, and vitreoretinal surgery. All experts were subjected to questions related to three topics: diagnostic-therapeutic pathway of IRD patients, essential requirements for gene therapy delivery centres, and standardized model for therapy delivery. All contributions were judged to be of equal value. Results: The panel identified: the steps of the diagnostic pathway to achieve early diagnosis; the essential criteria that delivery centres must possess in terms of experience, multidisciplinary team, and technical equipment; a standardized model for VN administration. A network of few centres was identified as the best organizational model for VN delivery since it would ensure the gaining of experience and clinical excellence. Conclusion: This paper provides a perspective that can be used as a starting point to standardize the diagnostic-therapeutic pathway of IRD patients and define the essential requirements that centres must meet for VN administration.

Capillary non-perfusion (CNP) is one of the key hallmarks of diabetic retinopathy (DR), which may develop both in the periphery and at the posterior pole. Our perspectives on CNP have extended with the introduction of optical coherence tomography angiography (OCTA) and ultra-widefield imaging, and the clinical consequences of peripheral and macular CNP have been well characterized. Fluorescein angiography (FA) continues to be the gold standard for detecting and measuring CNP, particularly when ultra-widefield imaging is available. OCTA, on the other hand, is a quicker, non-invasive approach that allows for a three-dimensional examination of CNP and may soon be regarded as an useful alternative to FA. In this review, we provide an updated scenario regarding the characteristics, clinical impact, and management of central and peripheral CNP in DR.

Abstract To evaluate differences in macular and optic disc circulation in patients affected by Wolfram Syndrome (WS) employing optical coherence tomography-angiography (OCTA) imaging. In this retrospective study, 18 eyes from 10 WS patients, 16 eyes of 8 patients affected by type I diabetes and 17 eyes from 17 healthy controls were enrolled. All patients were imaged through OCT and OCTA and vascular parameters, as perfusion density (PD) and vessel length density (VLD) were measured. OCTA showed reduced PD in WS patients at the macular superficial capillary plexus (SCP, 27.8 ± 5.3%), deep vascular complex (DVC, 33.2 ± 1.9%) and optic nerve head (ONH, 21.2 ± 9.1%) compared to both diabetic patients (SCP 33.9 ± 1.9%, P

Abstract To develop a novel scoring system aiming at guiding the differential diagnosis between macular neovascularization secondary to pachychoroid disease (pMNV) and neovascular age-related macular degeneration (AMD) in patients aged 50 years and older. In this retrospective study performed at University Vita-Salute San Raffaele (Milan, Italy) and Créteil University Eye Clinic (Créteil, France), we enrolled patients 50 years of age and older, visited between January 2017 and January 2019, who were diagnosed with either treatment-naïve pMNV or neovascular AMD. At the time of diagnosis, all patients underwent a comprehensive ophthalmologic evaluation, spectral-domain optical coherence tomography, fluorescein angiography, indocyanine green angiography, and optical coherence tomography angiography. Univariate comparison between pMNV and neovascular AMD groups was performed to identify the main clinical predictors for pMNV. The selected predictors were taken into a binomial logistic regression and eventually served as the basis for the development of InCASEOf scoring system. Receiver operating characteristic (ROC) curves were used to study the model performance. Forty-eight right eyes from 48 patients with pMNV and 39 right eyes from 39 patients with neovascular AMD were considered in this study. Age (+ 2 points), sex (+ 2 points), choroidal thickness (+ 2 points), early pachyvessels (+ 2 points), and evidence of MNV at OCTA (+ 3 points) turned out to be predictors for pMNV. Four additional factors significant at univariate analysis were considered: type 2 and type 3 MNVs and presence of intraretinal fluid (− 0.5 points each), and presence of subretinal fluid (+ 0.5 points). InCASEOf scoring system was built with a high score of 11.5 points. The cutoff value of 6.5 showed good accuracy in separating pMNVs from neovascular AMDs. InCASEOf is a straightforward clinical scoring system, accessible to comprehensive ophthalmologists, with the purpose of enabling easy distinction and expert-like diagnosis of pMNV and neovascular AMD in patients aged 50 years or older.

Purpose: Antioxidants have been lately postulated as supportive and prophylactic supplements for various retinal disorders, especially age-related macular degeneration (AMD). Forty-eight brands of such supplements containing lutein and zeaxanthin are available in India. The aim of the study was to assess the market leaders in supplements for ophthalmology in view of AREDS recommendations. Methods: Descriptive review of top-selling supplements for eye health were compared to the contents of the AREDS-recommended levels. Results: None of the top 10 selling brands had exact or near similar composition as recommended in the AREDS-2 study, which is the most widely accepted level-1 evidence in AMD prevention. Conclusion: Physicians prescribing these antioxidants, especially for the prevention of advanced AMD, should be vigilant and aware of the contents of the prescribed brands.

Graft-versus-host disease (GVHD) is characterized by tissue inflammation in the host following an allogeneic hematopoietic cell transplantation (HCT). The pathophysiology is complex and only incompletely understood yet. Donor lymphocyte interaction with the histocompatibility antigens of the host plays a crucial role in the pathogenesis of the disease. Inflammation may affect multiple organs and tissues, e.g., the gastrointestinal tract, liver, lung, fasciae, vaginal mucosa, and the eye. Subsequently, alloreactive donor-derived T and B lymphocytes may lead to severe inflammation of the ocular surface (i.e., cornea and conjunctiva) and the eyelids. Furthermore, fibrosis of the lacrimal gland may lead to severe dry eye. This review focuses on ocular GVHD (oGVHD) and provides an overview of current challenges and concepts in the diagnosis and management of oGVHD. Ophthalmic manifestations, diagnostic procedures, grading of severity and recommendations for ophthalmic examination intervals are provided. Management of ocular surface disease with lubricants, autologous serum eye drops, topical anti-inflammatory agents and systemic treatment options are described based on the current evidence. Ocular surface scarring and corneal perforation are severe complications of oGVHD. Therefore, ophthalmic screening and interdisciplinary treatment approaches are highly relevant to improve the quality of life of patients and to prevent potentially irreversible visual loss.

Purpose: Macular retinal pigment epithelium (RPE) hypopigmentation is a recently described very rare condition and its pathogenesis is not completely understood. We report the case of a 23-year-old female who presented with bilateral whitish, oval-shaped foveal lesions and we speculated about the possible etiopathogenetic origin. Observations: A 23-year-old female presented to our consideration for a routine ophthalmology visit. Visual acuity was 20/20 in both eyes. The fundus examination revealed a perifoveal choroidal nevus in the right eye and a bilateral yellowish, oval-shaped lesion centered on the fovea. Imaging tests (Spectral Domain-Optical Coherence Tomography, short wavelength and near-infrared autofluorescence) and functional tests (microperimetry and multifocal electroretinogram) were within normal limits, supporting the diagnosis of macular hypopigmentation without functional loss. Conclusions: A complex dysregulation of both choroidal and RPE with melanin loss may be responsible for this condition.

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.

Abstract Purpose To assess the rate of occurrence and the risk factors of postsurgical macular edema (PSME) in eyes with idiopathic epiretinal membrane (iERM) or full-thickness macular hole (FTMH). Methods Retrospective longitudinal analysis of all subjects scheduled for vitrectomy with or without combined cataract surgery over a 6-month period. Electronic medical charts and imaging data were analyzed preoperatively and at 1, 3 and 6 months after surgery. Results From 101 patients diagnosed with iERM or FTMH, 71 patients were eligible for the study. Forty-nine eyes with iERM (69.0%) and 22 eyes with FTMH (31.0%) underwent vitrectomy either isolated (31.0%) or combined with cataract extraction (69.0%). The overall rate of PSME was 26.7%, without differences between the two groups (P = 0.9479). Combined cataract extraction did not affect the overall occurrence of PSME rate in both groups (P = 0.9255 in FTMH and P = 0.8658 in iERM). If grouped by stage, eyes with stage 4 iERM though disclosed an increased rate of PSME (57.1%) compared to lower (1 to 3) stages (14.3%, P = 0.0021), particularly when combined with cataract surgery (71.4% vs. 15.4% in stages ≤ 3, P = 0.0021). The PSME odds ratio for a stage 4 iERM is 8 (95% CI: 1.933–33.1; P = 0.0041) compared to stages 3 and below. Conclusions PSME remains a clinically relevant and frequent event after surgery for iERM and FTMH. Patients with stage 4 iERM have an 8-fold higher likelihood of developing PSME in a 6-month postsurgical period compared to iERM in 1–3 stages, especially when combined with cataract extraction.

Abstract Optical coherence tomography angiography (OCTA) provides several data regarding the status of retinal capillaries. This information can be further enlarged by employing quantitative metrics, such as vessel density (VD). A mandatory preliminary step of OCTA quantification is image binarization, a procedure used to highlight retinal capillaries on empty background. Although several binarization thresholds exist, no consensus is reached about the thresholding technique to be used. In this study, we tested thirteen binarization thresholds on a dataset made by thirty volunteers. The aim was to assess the impact of binarization techniques on: (I) detection of retinal capillaries, assessed by the calculation of overlapping percentages between binarized and original images; (II) quantitative OCTA metrics, including VD, vessel tortuosity (VT) and vessel dispersion (Vdisp); (III) foveal avascular zone (FAZ) detection. Our findings showed Huang, Li, Mean and Percentile as highly reliable binarization thresholds (p

Abstract Outer retinal tubulations (ORT) are a relatively new finding characterizing outer retinal atrophy. The main aim of the present study was to describe ORT development in advanced age-related macular degeneration (AMD) and to assess its relationship with disease’s severity. Patients with advanced AMD characterized either by macular neovascularization or geographic atrophy, showing signs of outer retinal disruption or retinal pigment epithelium atrophy on structural optical coherence tomography (OCT) at the inclusion examination were prospectively recruited. All the patients underwent complete ophthalmologic evaluation, structural OCT scans and fundus autofluorescence imaging. The planned follow-up was of 3-years. Main outcome measures were ORT prevalence, mechanism of ORT formation, mean time needed for complete ORT formation, best-corrected visual acuity (BCVA), definitely decreased autofluorescence (DDAF) area, questionably decreased autofluorescence (QDAF) area, retinal layer thickness, foveal sparing, number of intravitreal injections. We also assessed the possible role of external limiting membrane (ELM) and Müller cells in ORT pathogenesis. Seventy eyes (70 patients) were included; 43 showed dry AMD evolving to geographic atrophy, while 27 displayed the features of wet AMD. Baseline BCVA was 0.5 ± 0.5 LogMAR, decreasing to 0.9 ± 0.5 LogMAR at the 3-year follow-up (p

Diabetic retinopathy (DR) is the most common complication of diabetes and has been historically regarded as a microangiopathic disease. Now, the paradigm is shifting toward a more comprehensive view of diabetic retinal disease (DRD) as a tissue-specific neurovascular complication, in which persistently high glycemia causes not only microvascular damage and ischemia but also intraretinal inflammation and neuronal degeneration. Despite the increasing knowledge on the pathogenic pathways involved in DR, currently approved treatments are focused only on its late-stage vasculopathic complications, and a single molecular target, vascular endothelial growth factor (VEGF), has been extensively studied, leading to drug development and approval. In this review, we discuss the state of the art of research on neuroinflammation and neurodegeneration in diabetes, with a focus on pathophysiological studies on human subjects, in vivo imaging biomarkers, and clinical trials on novel therapeutic options.

Direct leukemic infiltration of the eye is most frequently associated with acute lymphoblastic leukemia (ALL), probably due to its well-known central nervous system (CNS) tropism. Systemic treatment alone may not be sufficient for intraocular leukemia. Data on local treatment are scarce. Here, we present two cases of intraocular ALL treated with intravitreal methotrexate (MTX). Initially, anatomical improvement and visual stability were observed. The first patient experienced anatomical and visual worsening after a year of treatment. Treatment was withheld after 2 months for the second patient due to poor systemic conditions. Corneal toxicity and intraocular pressure elevation were observed in the first case. In both cases, eye involvement was associated with CNS or systemic relapse. This highlights the importance of incorporating ocular disease management in a comprehensive approach to therapy. Our experience corroborates previous findings on MTX injections as an effective and safe therapeutic option for intraocular leukemia. Further evidence is needed to consolidate the use of intravitreal MTX to treat such a debilitating localization of leukemia.

BackgroundDiabetic Macular Edema (DME) is the most common cause of vision loss in diabetic patients. Currently, the Vascular Endothelial Growth Factor inhibitors (anti-VEGFs) are used as the first line of DME treatment and corticosteroid implants are usually used as a second-line treatment. These implants are a safe and effective therapeutic option that can improve the quality of life of DME patients by reducing the intravitreal injections number. We determined the economic impact related to DME, also from the social perspective, and the consequences of the increased use of the dexamethasone implant.MethodsThe analysis compares two scenarios: the first based on the current rate of recourse to the therapeutic alternatives available in the Italian healthcare setting (as is) and the second based on the assumption of an increased recourse to dexamethasone implants (to be). The results are expressed both in terms of the resource absorption associated with the two scenarios and in terms of the cost differential yielded by their comparison.ResultsThe increased use of the dexamethasone implant allows considerable savings in terms of healthcare professionals' time, follow-up and productivity lost by patients/caregivers. These savings would reduce healthcare costs for the management of DME patients in Italy by €2,058,238 in 5 years.ConclusionsTo optimize the healthcare resources allocation, it is necessary to implement treatments that yield not only cost reductions but also a clinical benefit for patients. The dexamethasone implant use is an example of DME management that generates value for patients, health system and society.

Purpose: To report a case of progressive resolution of exudation in a patient affected by perifoveal vascular anomalous complex (PVAC) undergoing topical diclofenac therapy. Observations: A 74-year-old man presented to our department with visual decrease in his right eye lasting six months. Lack of clinical history of arterial hypertension, diabetes, or any other systemic or local vasculopathy, together with retinal multimodal imaging, led to the diagnosis of exudative (e)PVAC. Serial spectral-domain optical coherence tomography (SD-OCT) examinations documented a resolution of intraretinal exudation after one-month topical diclofenac therapy. Conclusion and Importance: Initiation of topical diclofenac was associated with resolution of exudation, therefore we hypothesize its potential role in the treatment of ePVAC.

Purpose: Occult Macular Dystrophy (OMD) is an autosomal dominant inherited retinal dystrophy caused by mutations in the retinitis pigmentosa 1-like 1 (RP1L1) gene. The present study describes a novel RP1L1 variant, identified for the first time in two Italian sisters diagnosed with OMD, along with multimodal imaging features, including Optical Coherence Tomography (OCT) Angiography. Methods: We performed multimodal imaging including spectral-domain OCT, blue light autofluorescence (BAF), infrared autofluorescence (IRAF), swept-source OCT Angiography (OCTA), full-field and multifocal electroretinography. Genetic analysis was performed using Next-Generation Sequencing. Pathogenic potential of nonsynonymous novel variants was scored with two in silico algorithms. Results: Proband 1 (P1) and proband 2 (P2) were two Italian sisters of 61 and 56 years old. Both reported a history of progressive visual loss without fundoscopic alterations. P1 reported a 4-year history of rapid visual function worsening, and her best-corrected visual acuity (BCVA) was counting fingers in both eyes. P2 reported a 20-year history of mild but progressive visual acuity loss, and her BCVA was 1/10 and 2/10 respectively in her right and left eye. Structural OCT displayed disorganization of outer retinal bands at the macula and foveal cavitation; loss of foveal photoreceptors was remarkably evident on en-face OCT slabs. OCTA quantitative analysis found that vessel density was reduced both at SCP and DCP while choriocapillaris blood flow was relatively spared. Genetic analysis found the same rare dominant c.2873G > C, p.Arg958Pro variant in the RP1L1 gene. The substitution was regarded as moderately radical according to Grantham score while PolyPhen2 classified the amino acidic substitution as probably damaging. Conclusions and importance: Our study expands the mutational spectrum of RP1L1 gene: the rare c.2873G > C, p.Arg958Pro missense variant may be considered a new pathogenic variant for OMD, the first to be identified exclusively in an Italian family. Moreover, our quantitative OCTA data suggest that OMD is characterized by a rarefaction of superficial and deep capillary plexus.

Purpose: To report a case of a 7-year-old male patient with bilateral choroidal caverns (CC) and pachychoroid. Observations: During the Italian COVID-19 lockdown, a 7-year old boy presented with bilateral vision decline that had started two weeks before. Structural optical coherence tomography revealed pachychoroid and CC bilaterally. Other ocular examinations were negative. The patient had an apprehensive personality and symptoms quickly resolved when he was provided with non-prescription glasses; his visual disturbances were thus considered to be functional and factitious. Conclusions and Importance: Our patient's symptoms remind us that the distress imposed upon psychologically frail subjects by the COVID-19 pandemic may have multifaceted manifestations. The discovery of CC in a pediatric patient with healthy eyes presents us with new questions about the processes of degeneration thought to be the cause for CC. Further studies are needed to estimate the prevalence of CC in the general adult and pediatric populations, as well as in patients with chorioretinal diseases.

Abstract Optical coherence tomography (OCT) angiography (OCTA) is a non-invasive tool for the in-vivo study of the intraretinal vascular network. It is based on the analysis of motion particles within the retina to reconstruct the paths followed by the erythrocytes, i.e. retinal capillaries. To date, qualitative and quantitative information are based on the morphological features disclosed by retinal capillaries. In the present study, we proposed new quantitative functional metrics, named Total Flow Intensity (TFI), Active Flow Intensity (AFI), and Volume-related Flow Intensity (VFI), based on the processing of the blood flow signal detected by OCTA. We studied these metrics in a cohort of healthy subjects, and we assessed their clinical utility by including a cohort of age-matched patients affected by Stargardt disease. Moreover, we compared TFI, AFI, and VFI to the widely used vessel density (VD) parameter. TFI, AFI, and VFI were able to describe in detail the different properties of the retinal vascular compartment. In particular, TFI was intended as the overall amount of volumetric retinal blood flow. AFI represented a selective measure of voxels disclosing blood flow signal. VFI was developed to put in relationship the volumetric blood flow information with the not vascularized retinal volume. In conclusion, TFI, AFI, and VFI were proposed as feasible functional OCTA biomarkers based on the analysis of retinal blood flow signal.

Abstract There is a lack of treatment aimed at the regression of reticular pseudodrusen (RPD) secondary to age-related macular degeneration (AMD). The aim of this prospective, pilot study is to evaluate the safety and short-term efficacy of subthreshold laser treatment (SLT) in patients affected by RPD secondary to dry AMD (dAMD). Twenty eyes of 20 patients (mean age 78.4 ± 6.8 years) with RPD secondary to dAMD were prospectively enrolled. All patients were treated in an extrafoveal area of 1.27 mm2 using end-point management yellow subthreshold laser and followed for 3 months. Best-corrected visual acuity was 0.140 ± 0.09 LogMAR at the baseline and no changes were observed during the follow-up (p = 0.232). No significant worsening was disclosed before and after the treatment analyzing the macular sensitivity of the treated area (p = 0.152). No topical and/or systemic side effects were disclosed during the 3-month follow-up. The distribution among the RPD stages changed after the treatment (p