Integrating Machine Learning and Traditional Survival Analysis to Identify Key Predictors of Foveal Involvement in Geographic Atrophy.

Purpose: The purpose of this study was to investigate the incidence of foveal involvement in geographic atrophy (GA) secondary to age-related macular degeneration (AMD), using machine learning to assess the importance of risk factors. Methods: Retrospective, longitudinal cohort study. Patients diagnosed with foveal-sparing GA, having GA size ≥ 0.049 mm² and follow-up ≥ 6 months, were included. Baseline GA area, distance from the fovea, and perilesional patterns were measured using fundus autofluorescence. Optical coherence tomography assessed foveal involvement, structural biomarkers, and outer retinal layers thickness. Onset of foveal involvement was recorded. Foveal survival rates were estimated using Kaplan-Meier curves. Hazard ratios (HRs) were assessed with mixed model Cox regression. Variable Importance (VIMP) was ranked with Random Survival Forests (RSF), with higher scores indicating greater predictive significance. Results: One hundred sixty-seven eyes (115 patients, average age = 75.8 ± 9.47 years) with mean follow-up of 50 ± 29 months, were included in this study. Median foveal survival time was 45 months (95% confidence interval [CI] = 38-55). Incidences of foveal involvement were 26% at 24 months and 67% at 60 months. Risk factors were GA proximity to the fovea (HR = 0.97 per 10-µm increase, 95% CI = 0.96-0.98), worse baseline visual acuity (HR = 1.37 per 0.1 LogMAR increase, 95% CI = 1.21-1.53), and thinner outer nuclear layer (HR = 0.59 per 10-µm increase, 95% CI = 0.46-0.74). RSF analysis confirmed these as main predictors (VIMP = 16.7, P = 0.002; VIMP = 6.2, P = 0.003; and VIMP = 3.4, P = 0.01). Lesser baseline GA area (HR = 1.09 per 1-mm2 increase, 95% CI = 1.01-1.16) and presence of a double layer sign (HR = 0.42, 95% CI = 0.20-0.88) were protective but less influential. Conclusions: This study identifies anatomic and functional factors impacting the risk of foveal involvement in GA. These findings may help identify at-risk patients, enabling tailored preventive strategies.

Spontaneous remission of choroidal involvement by chronic myelomonocytic leukemia: a case report.

Chronic myelomonocytic leukemia (CMML) is a rare hematological disorder characterized by variable risk of evolution to acute myeloid leukemia; to date, allogeneic stem cell transplantation is the only curative treatment. We report a case of choroidal involvement in a woman affected by CMML and presenting only with visual impairment. The patient was initially evaluated for an intensive therapeutic approach, but after biopsy the ocular lesion spontaneously regressed. Thus a "watch and wait" strategy was preferred. One year and a half after initial diagnosis, the patient is alive, with stable hematological disease and without any ocular involvement. Therefore, a close, not invasive follow up could be useful to tailor treatment for patients affected by single ocular lesions in CMML.

Unraveling the Spectrum of Uveitis: Insights from an Epidemiological Study in a National Referral Center in Northern Italy.

PURPOSE: Uveitis embraces a heterogeneous group of vision-threatening inflammatory conditions. Understanding uveitis epidemiology, etiology, and clinical findings is fundamental for a prompt diagnosis and optimal patient management. The aim of the study is to report the epidemiology of uveitis in a national referral center in Northern Italy and investigate the visual prognosis. METHODS: This retrospective study was conducted at Uveitis Service (Ospedale San Raffaele) between June 2016 and May 2023. Demographic data, clinical characteristics, and etiological diagnoses of uveitis patients were collected, and visual prognosis was longitudinally explored. RESULTS: 1105 patients with uveitis were included in the study, while 47 patients presented neoplastic masquerade syndrome and have been excluded. The population had a slight majority of females (M/F ratio = 0.76), mean age was 47 years. 25% presented infectious uveitis, primarily due to herpetic etiology, toxoplasmosis, and tuberculosis. Non-infectious uveitis was the most prevalent diagnosis (38%), with sarcoidosis, HLA-B27-associated uveitis, and Fuch's uveitis as prominent causes. Anatomically, anterior segment was most frequently involved (41%). Significant improvement in visual acuity was observed at follow-up, particularly in patients with infectious uveitis. CONCLUSIONS: Our study sheds light into the epidemiological landscape of uveitis in Northern Italy, reflecting changing patterns due to factors such as migration and changing sexual habits. In particular, higher percentages of syphilis have been observed, compared to other European reports. The distribution of non-infectious uveitis reflects other epidemiological European series. Higher percentages of neoplastic masquerade syndromes support the need of early recognition. Our findings offer precious insights for uveitis epidemiology and daily clinical practice.

Photoreceptor Integrity in MEWDS: Longitudinal Structure-Function Correlations.

Purpose: The purpose of this study was to investigate structure-function correlations in multiple evanescent white dot syndrome (MEWDS) using microperimetry (MP) and spectral-domain optical coherence tomography (SD-OCT). Methods: Single-center prospective observational study including 14 eyes from 13 patients with MEWDS monitored over a median of 49.5 days (interquartile range = 29-92 days). Investigations focused on best-corrected visual acuity (BCVA), foveal granularity, and the Photoreceptor Reflectivity Ratio (PRR) as a measure of photoreceptor integrity. MP assessed average retinal threshold sensitivity (RTS) and bivariate contour ellipse area (BCEA) for fixation stability. A linear mixed model was used to test associations and interactions among RTS, time, and clinical variables. A hierarchical linear mixed model was used to analyze structure-function relationships, addressing both individual and location-specific variations. Results: Overall, 2340 MP locations were tested. PRR revealed a transient decrease within 30 days post-presentation, indicative of early photoreceptor disruption, followed by a progressive increase, signaling recovery. Significantly lower foveal sensitivity (RTS = 14.8 ± 7.4 vs. 22.5 ± 4.4 decibel [dB], P = 0.04) and increased fixation spread (63% BCEA = 1.26 ± 0.97 vs. 0.48 ± 0.35 deg2, P = 0.06) were noted in eyes with foveal granularity compared to those without. A significant increase in RTS was demonstrated over time (0.066 dB/day, P < 0.001), with a central-to-peripheral gradient of improvement. The interaction between follow-up time and baseline BCVA (P < 0.001) indicated more rapid improvement in eyes with worse initial vision. There was a robust, nonlinear association between PRR and RTS across all tested locations (P < 0.001), becoming asymptotic for sensitivity losses exceeding 20 dB. Conclusions: Photoreceptor reflectivity accurately aligned with visual function in MEWDS on longitudinal examinations. The central-to-peripheral gradient of improvement may suggest specific vulnerabilities underlying the area around the disc.

Rate and Predictors of Misclassification of Active Diabetic Macular Edema as Detected by an Automated Retinal Image Analysis System.

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 < 0.001), and presence of hard exudates (p < 0.001), microaneurysms (p < 0.001), or epiretinal membrane (p = 0.06). CONCLUSIONS: The sensitivity of ARIAS was diminished in older patients and those without DME-related fundus lesions, while the specificity was reduced in cases with a history of inactivated DME. ARIAS performed well in screening for naïve DME but is not effective in surveillance inactivated DME.

Central Bouquet Hemorrhages in Pathologic Myopia: Clinical Characteristics and Prognostic Relevance.

PURPOSE: To compare the clinical implications of central bouquet hemorrhages (CBHs) to primarily subretinal hemorrhages, both occurring in the setting of pathologic myopia with lacquer crack formation. DESIGN: Multicenter retrospective cohort study. PARTICIPANTS: Twenty-five eyes (11 primarily subretinal hemorrhages and 14 CBH) were monitored over a median of 35 (interquartile range [IQR], 9.50-54) months. MAIN OUTCOMES MEASURES: Comprehensive ophthalmic examinations and OCT were reviewed. The study employed linear mixed-effects models to compare the impact of CBH versus primarily subretinal hemorrhages on baseline visual acuity (VA), rate of VA improvement, and final VA, adjusting for the follow-up period. Times of hemorrhages reabsorbtion and rate of ellipsoid zone (EZ) layer disruption on OCT were recorded. RESULTS: Eyes with CBH exhibited significantly worse baseline VA (0.93 ± 0.45 logarithm of the minimum angle of resolution [logMAR]; 20/160 Snellen vs. 0.36 ± 0.26 logMAR [20/50 Snellen], P < 0.001), a slower rate of VA improvement (P = 0.04), and a trend toward worse final VA (0.48 ± 0.47 logMAR [20/60 Snellen] vs. 0.16 ± 0.16 logMAR [20/30 Snellen], P = 0.06) compared with eyes with primarily subretinal hemorrhages. The CBH group experienced longer median reabsorption times (10 [IQR, 4.6-23.3] months vs. 2.3 [IQR, 2-3.2] months), and a higher prevalence of EZ layer disruption (86% vs. 0%), than the group with primarily subretinal hemorrhages. Central bouquet hemorrhage reabsorption was followed by the appearance of vertical hyperreflective lines in the central fovea in 67% of eyes, persisting for up to 6 years of follow-up. CONCLUSIONS: Central bouquet hemorrhage signifies a distinct condition in pathologic myopia, characterized by worse visual outcomes, prolonged structural impact, and possible irreversible damage, compared with primarily subretinal hemorrhages. Central bouquet hemorrhage regression should be taken into account in the differential diagnosis of vertical hyperreflective lesions in the central fovea on OCT in eyes with pathologic myopia. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Assessing Diabetic Retinopathy Staging With AI: A Comparative Analysis Between Pseudocolor and LED Imaging.

Purpose: To compare the diagnostic performance of artificial intelligence (AI)-based diabetic retinopathy (DR) staging system across pseudocolor, simulated white light (SWL), and light-emitting diode (LED) camera imaging modalities. Methods: A cross-sectional investigation involved patients with diabetes undergoing imaging with an iCare DRSplus confocal LED camera and an Optos confocal, ultra-widefield pseudocolor camera, with and without SWL. Macula-centered and optic nerve-centered 45 × 45-degree photographs were processed using EyeArt v2.1. Human graders established the ground truth (GT) for DR severity on dilated fundus exams. Sensitivity and weighted Cohen's weighted kappa (wκ) were calculated. An ordinal generalized linear mixed model identified factors influencing accurate DR staging. Results: The study included 362 eyes from 189 patients. The LED camera excelled in identifying sight-threatening DR stages (sensitivity = 0.83, specificity = 0.95 for proliferative DR) and had the highest agreement with the GT (wκ = 0.71). The addition of SWL to pseudocolor imaging resulted in decreased performance (sensitivity = 0.33, specificity = 0.98 for proliferative DR; wκ = 0.55). Peripheral lesions reduced the likelihood of being staged in the same or higher DR category by 80% (P < 0.001). Conclusions: Pseudocolor and LED cameras, although proficient, demonstrated non-interchangeable performance, with the LED camera exhibiting superior accuracy in identifying advanced DR stages. These findings underscore the importance of implementing AI systems trained for ultra-widefield imaging, considering the impact of peripheral lesions on correct DR staging. Translational Relevance: This study underscores the need for artificial intelligence-based systems specifically trained for ultra-widefield imaging in diabetic retinopathy assessment.

Multimodal Imaging of Vitreo-Retinal Lymphoma: A Comprehensive Review.

PURPOSE: Vitreoretinal lymphoma (VRL) is a rare lymphoma affecting the vitreous and the retina. Clinical diagnosis is challenging and often delayed and may lead to aggravated prognosis. This study aims to review multimodal imaging findings in VRL. METHODS: We performed a comprehensive narrative review of the multimodal imaging findings that might be useful in the detection of VRL lesions. RESULTS: The most frequent ocular manifestations of VRL are vitritis, and retinal and sub-retinal Pigmented Epithelium (RPE) infiltrations. Color Fundus Photography (CFP) detects vitreous haze, optic nerve, retinal and sub-RPE infiltration. Ultra-wide field imaging allows visualization of different patterns of vitreous haze and monitoring of VRL evolution through the detection of chorio-retinal atrophy (CRA). Fundus Autofluorescence shows granular hypo- and hyper-autofluorescent pattern. Optical Coherence Tomography (OCT) reveals vitreous cells, vertical hyper-reflective lesions and sub-RPE infiltrates. Fluorescein Angiography (FA) shows hypo or hyperfluorescent round lesions at the late stages of the examination, while Indocyanine Green Angiography (ICGA) detects round areas of focal hypo-fluorescence in the early phases that gradually enlarge in the late phases. B-scan ultrasonography detects vitreous opacities and homogeneous hyperreflective corpuscular material in the vitreous, and is a strongly recommended tool in suspecting VRL and is particularly useful when vitreous haze is impeding retinal examination. CONCLUSION: Diagnostic vitrectomy with cytopathological analysis remains the gold standard for VRL diagnosis, however multimodal imaging allows the identification of suggestive retinal and vitreal lesions for early suspicion, diagnosis, and treatment and monitoring disease progression and response to treatment.

Real-world experience with fluocinolone acetonide intravitreal implant in patients with diabetic macular edema.

OBJECTIVES: to evaluate long-term effectiveness and safety of fluocinolone acetonide (FAc) implant used as second-line treatment in patients with persistent diabetic macular edema (DME). METHODS: retrospective data chart review of 241 pseudophakic eyes of 178 patients treated with FAc from July 2017 to December 2021 in 10 medical retinal units in Italy. The primary endpoint was the change of best-corrected visual acuity (BCVA) and central macular thickness (CMT) at 2 years. A Student's paired t-test was used. Additional therapies for DME and intraocular pressure (IOP)-related events were also evaluated. RESULTS: efficacy of FAc was assessed in a subset of 111 eyes with at least 24 months of follow-up. Mean BCVA increased at 2 years by 5.1 ETDRS letters (95%CI = 2.6-7.5; p < 0.001) while mean CMT decreased by 189 µm (95% CI 151-227; p < 0.001). Thirty-eight of these eyes (34.2%) needed additional intravitreal treatments, mainly anti-VEGF. Safety was evaluated on the entire cohort of 241 eyes treated with FAc. Overall, 66 eyes (27.4%) required emergent IOP-lowering medications (typically within the first-year post FAc) while 14 eyes (5.8%) underwent trabeculectomy, mostly during the second year of follow-up. CONCLUSION: FAc implant provides a substantial long-term functional and anatomical benefit when used as second-line treatment in eyes with DME. IOP rise can be adequately managed with topical agents although some eyes may require IOP-lowering surgery.

Anterior segment involvement in vitreoretinal lymphoma: clinical manifestations, molecular findings and in vivo confocal microscopy.

BACKGROUND: Intermediate and posterior manifestations of vitreoretinal lymphoma (VRL) are well characterised. However, there is limited information on anterior segment involvement in VRL. This study aimed to describe the anterior manifestations of VRL, and their association with molecular testing. METHODS: Retrospective analysis of patients with biopsy-proven VRL. Study variables included anterior segment manifestations, findings from slit-lamp photos and in vivo confocal microscopy (IVCM) when available. MYD88 L265P mutation and cytology in the aqueous humour, retinal and systemic findings were also analysed. RESULTS: The analysis included 108 eyes of 55 VRL patients. Anterior segment involvement was present in at least one visit in 55 eyes (51%) of 33 patients (60%); it included keratic precipitates (dendritiform with branching and irregular margins in 33 eyes, dust-like in 16 eyes and large granulomatous in 12 eyes), cells in the anterior chamber (51 eyes) and posterior synechiae (2 eyes). IVCM was available for 41 eyes and showed different morphologies of keratic precipitates, including floral, spikes and mulberry patterns (66%, 56% and 20%, respectively). MYD88 L265P mutation in the aqueous humour was detected in 10/21 (48%) eyes with no anterior segment involvement and 24/37 (65%) eyes with anterior segment involvement. CONCLUSIONS: Anterior segment manifestations are often present in VRL and include dendritiform and dust-like keratic precipitates. IVCM in VRL can identify different patterns associated with keratic precipitates. MYD88 L265P mutation in the aqueous humour of VRL patients can also be found in eyes without significant anterior segment involvement.

Rate and associations of inner retinal thinning in eyes with retinal vein occlusion and regressed macular oedema.

PURPOSE: To investigate the associations between visual acuity (VA) and structural optical coherence tomography (OCT) features in retinal vein occlusion (RVO) eyes after cystoid macular oedema (CMO) regression and to assess whether inner retinal thinning is progressive. METHODS: Retrospective observational study of RVO eyes with regressed CMO for at least 6 months. OCT scans at CMO regression were analysed, and features were correlated with VA at that visit. The inner retinal thickness was longitudinally compared between RVO and unaffected fellow eyes (controls) with linear mixed models. The rate of inner retinal thinning was obtained as the interaction term between disease status and time. Associations between inner retinal thinning and clinical characteristics were explored. RESULTS: Thirty-six RVO eyes were followed for 34.2 ± 21.1 months after CMO regression. The presence of ellipsoid zone disruption (regression estimate[standard error(SE)] = 0.16[0.04] LogMAR vs. intact, p < 0.001) and lower inner retinal thickness (regression estimate[SE] = -0.25[0.12] LogMAR for 100-µm increase, p = 0.01) were associated with worse VA. The inner retinal thickness decreased faster in RVO than controls (rate of retinal thinning -0.27 ± 0.09 µm/month vs. -0.08 ± 0.11 µm/month, p = 0.01). Macular ischaemia was associated with a faster rate of retinal thinning (interaction term macular ischaemia*follow-up time, p = 0.04). CONCLUSION: Inner retinal and photoreceptors' layers integrity are associated with better visual acuity once CMO resolves. RVO eyes undergo progressive inner retinal thinning after CMO regression, faster in eyes with macular ischaemia.

Validation of Esaso Classification of Diabetic Maculopathy.

PURPOSE: To test reliability and reproducibility of ESASO morphologic OCT-based classification of diabetic maculopathy (DM). METHODS: This is a multi-center cross-sectional study including a coordination center (CC) and 18 participating centers (PCs). After instruction on the correct use of ESASO Classification, the validation process was carried out in two consecutive stages. In the first retrospective phase, we evaluated the concordance between PCs and CC in the staging of OCT images collected during PCs' daily activity (608 images). In a second prospective phase, we analyzed the inter-observer agreement of staging assigned by each PCs to OCT images selected by the CC (22 images). RESULTS: The overall concordance achieved in the retrospective phase was 89.8% (Kappa = 0.83 (95% CI: 0.78-0.87); p<0.0001). In 99.5% of cases, concordance did not differ by more than one stage. In the prospective phase, PCs reached an inter-operator agreement of 93.0% (Krippendorff's Alpha = 0.953, 95% CI: 0.929-0.977, p<0.0001). Any discrepancy among the 22 images was within one stage. CONCLUSION: The results achieved in this study confirm that ESASO OCT-based Classification can be considered as an easy and reproducible method to stage DM during clinical practice. A diffused use of a common and validated method to describe the progression of retinal damage in DM may offer several clinical and scientific advantages.

From diagnosis to prognosis: A paradigm shift for multimodal imaging in assessing diabetic macular edema.

Diabetic macular edema (DME) is one of the leading causes of visual impairment in patients with diabetes. Multimodal imaging (MMI) has allowed a shift from DME diagnosis to prognosis. Although there are no accepted guidelines, MMI may also lead to treatment customization. Several study groups have tried to identify structural biomarkers that can predict treatment response and long-term visual prognosis. The purpose of this editorial is to review currently proposed optical coherence tomography (OCT) and optical coherence tomography angiography (OCT-A) biomarkers.

Clinical and imaging biomarkers of response to intravitreal dexamethasone implant in eyes with non-infectious uveitic macular oedema.

OBJECTIVE: To investigate clinical and spectral-domain optical coherence tomography (SD-OCT) biomarkers correlating with pre-injection visual acuity (VA), post-injection VA, and the likelihood of macular oedema (MO) regression following dexamethasone (DEX) implant injection in non-infectious uveitic (NIU) patients. METHODS: Patient data from Uveitis Services in Milan, Paris, and Berlin were analysed. Eligible participants were NIU patients aged >18 years with MO as the primary indication for DEX treatment. SD-OCT scans and clinical data were collected at the time of DEX injection (pre-injection visit) and after 3 months (post-injection visit). Multivariable regression models, adjusted for pre-injection VA and lens status, were employed to explore associations. MO regression was defined as the absence of intraretinal/subretinal fluid at the post-injection visit. RESULTS: Our analysis comprised data from 173 DEX treatments, encompassing 103 eyes from 80 patients, with 38 eyes (37%) receiving repeated DEX injections. The absence of the ellipsoid zone (EZ) layer and disorganisation of the inner retinal layers (DRIL) were associated with worse pre- (+0.19 LogMAR, 95% CI 0.01-0.38, p = 0.06, and +0.10 LogMAR, 95% CI 0.02-0.21, p = 0.01) and post-injection VA (+0.33 LogMAR, 95% CI 0.08-0.57, p = 0.01, and +0.17 LogMAR, 95% CI 0.01-0.32, p = 0.04). EZ disruption and DRIL increased significantly (p = 0.01 and p = 0.04), and the chance of gaining ≥5 letters declined in eyes undergoing repeated DEX (p = 0.002). The rate of MO regression after each DEX was 67%. Prolonged MO duration (OR = 0.75/each year, p = 0.02) was associated with reduced likelihood of MO regression. Subretinal fluid was associated with higher rate of MO regression (OR = 6.09, p = 0.01). CONCLUSION: Integrity of the inner and outer retina is associated with better visual response to DEX. Long-standing or recurrent MO is associated with less chance of both visual and anatomic response. Timely treatment is necessary to maximise the outcomes of MO in NIU patients.

Acute atrophic evolution of drusenoid pigment epithelium detachment after photobiomodulation.

PURPOSE: To report the acute onset of macular atrophy soon after photobiomodulation (PBM) administration in a patient with intermediate age-related macular degeneration (AMD). METHODS: Optical coherence tomography (OCT) was performed in the study eye before and after PBM. RESULTS: A patient with drusenoid pigment epithelium detachment (D-PED) underwent PBM. A few weeks after PBM the D-PED collapsed, resulting in incomplete retinal pigment epithelium and outer retinal atrophy with visual acuity worsening. CONCLUSION: Thinning of the outer retinal layers over a D-PED and posterior hypertrasmission may represent bad prognostic factors for PBM, accelerating the lesion's natural history towards atrophic evolution.

Morphometric Risk Factors for Drusenoid Pigment Epithelium Detachment Collapse and Retinal Pigment Epithelium Atrophy Expansion.

Purpose: The purpose of this study was to investigate factors associated with drusenoid pigment epithelium detachment (dPED) growth rate, incidence of dPED collapse, and retinal pigment epithelium (RPE) atrophy enlargement rate following dPED collapse and their impact on visual acuity (VA). Methods: This was a retrospective longitudinal study on 44 eyes. Serial spectral-domain optical coherence tomography (SD-OCT) and fundus autofluorescence (AF) imaging were performed. Qualitative features and quantitative dPED-related metrics were assessed. The surface-to-volume ratio (S/V) was computed to evaluate dPED shape irregularity. AF imaging was utilized to measure RPE atrophy area in eyes experiencing dPED collapse. Regression models were used to analyze associations among VA, dPED growth rate, and RPE atrophy enlargement rate. Cox regression was used to identify risk factors for dPED collapse. Results: Significant correlations were observed between dPED area, surface, and volume (P < 0.05 for all pairs). The dPED metrics were inversely correlated with the S/V. Incidence of dPED collapse was 22 per 100 eye-years over a mean follow-up of 59 ± 41 months. Eyes experiencing collapsed dPED had worse baseline VA (P < 0.001). RPE hypertransmission (hazard ratio [HR] = 3.68, P = 0.004) and hyper-reflective foci (HR = 3.45, P = 0.02) were risk factors for dPED collapse; a higher S/V ratio was protective (HR = 0.78, P = 0.03). A faster rate of RPE atrophy enlargement was associated with a faster rate of dPED volume increase (r = 0.47, P = 0.02) and worse VA over time (P = 0.02). Conclusions: Risk stratification in patients with dPED can be aided by identifying risk factors for dPED collapse. Identifying factors associated with RPE atrophy enlargement may have implications for treatment decision making.

A comprehensive overview of diagnosis, imaging and treatment of vitreoretinal lymphoma.

Vitreoretinal lymphoma (VRL) is a rare B-cell intraocular neoplasia characterized by poor long-term prognosis and lack of effective therapies. It mainly involves the vitreous humor, the retina, and the retinal pigment epithelium (RPE), although anterior segment involvement can occur. VRL is classified as a lymphoma of immune privileged sites, along with testis lymphoma and primary central nervous system lymphoma (PCNSL). VRL and PCNSL are strictly connected indeed: 80% of VRL develop PCNSL, while 20% of patients with PCNSL present VRL during natural history of lymphoma. Due to the lack of worldwide consensus about diagnosis, therapy, and follow-up timing, VRL represents one of the most challenging ocular affections.VRL commonly masquerades as a posterior uveitis, and misdiagnosis often occurs because of partial response to topical steroids. Gold standard for diagnosis is cytological analysis of vitreous humor. However, this technique lacks sensitivity and supplemental molecular analyses can improve the diagnostic process. Multimodal imaging allows ophthalmologists to empower their clinical suspicion and a comprehensive examination can highlight typical features of VRL and justify further invasive procedures.There is no consensus about VRL therapy, and none of the therapeutical scheme has demonstrated to prevent cerebral involvement and improve patient's overall survival. Intravitreal injections of chemotherapeutics drugs, ocular radiation therapy and systemic chemotherapy can be considered in the treatment of VRL. Once cerebral involvement occurs, systemic chemotherapy must be included in the treatment as a life-saving therapy. Further multicentric studies are required to find out the best treatment of patients with VRL.

Presumed Müller Cell Activation in Multiple Evanescent White Dot Syndrome.

Purpose: The purpose of this study was to investigate the foveal changes occurring in multiple evanescent white dot syndrome (MEWDS) using multimodal imaging techniques with a specific focus on hyper-reflective dots (HRDs). Methods: This was a retro-prospective observational study including 35 eyes with active MEWDS. Structural and en face optical coherence tomography (OCT) was performed, with follow-up visits at 2 weeks, 6 weeks, and 2 months from baseline. HRD percentage area (HRD % area) was calculated in a 600 µm fovea centered circle on en face OCT, after background subtraction and image binarization. HRD % area was compared with 23 fellow control eyes. Longitudinal changes in the HRD % areas were assessed using repeated-measure statistics. Results: HRDs were observed as scattered hyper-reflective spots on the vitreoretinal interface on en face OCT images, colocalizing with HRDs or vertical hyper-reflective lines on structural OCT images. The baseline evaluation showed a significantly higher HRD % area in MEWDS eyes compared to fellow eyes (0.10 ± 0.03 vs. 0.08 ± 0.04, P = 0.01). The HRD % area correlated positively with LogMAR visual acuity and inversely with the duration of symptoms. Longitudinal analysis revealed a significant reduction in the HRD % area over time. There was no significant interaction between the rate of HRD disappearance and clinical or demographic factors at baseline. Conclusions: As HRD potentially represents the end-feet projections of activated Müller cells on the retinal surface, this study supports the involvement of Müller cells in the pathogenesis of the disease. The findings highlight the potential of en face OCT imaging for monitoring the progression of MEWDS.