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

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

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.

Posner-Schlossman Syndrome European Study Group: study protocol and baseline patients characteristics of a multicentre study.

BACKGROUND: The aim of the Posner-Schlossman Syndrome European Study Group (PSS-ESG) is to acquire a comprehensive dataset of European patients with PSS. Here, we present the first report on the study protocol and the clinical findings of the patients at baseline. METHODS: The PSS-ESG is a retrospective, multicentre study designed to evaluate patients with PSS. The study, designed and driven by a European Expert Committee includes three datasets: (1) the baseline, (2) the follow-up and (3) the intraocular pressure (IOP)/glaucoma dataset. RESULTS: A total of 11 centres adhered to the PSS-ESG and 107 patients were included (68 males, 39 females) mostly Caucasian (93.4%). At uveitis onset, the patient's age ranged between 11 and 76 years, (mean age: 42±15 years).Best-corrected visual acuity was >0.5 in 80.3% of the eyes, IOP was >40 mm Hg in 44% of the eyes. Keratic precipitates were found in 78.5% of the eyes. No flare or cells in anterior chamber were detected in 56% and 53% of the cases, respectively. PCR analysis on aqueous sample was positive for cytomegalovirus-DNA in 50.6% out of the 81 tested patients. CONCLUSIONS: The PSS-ESG is the first multicentre study aimed to collect a comprehensive dataset of patients with PSS in non-Asian countries. A middlde-aged Caucasian male with a low-grade anterior chamber inflammation, keratic precipitates, preserved visual acuity and marked increased in IOP seemed to be the standard PSS patient across the 11 uveitis and glaucoma centres participating in the PSS-ESG.

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.

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.

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

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

Ocular syphilis masquerading as CMV retinitis in a transplanted patient.

BACKGROUND: Syphilis has historically been referred to as "the great imitator", for the extent of disease manifestations secondary to infection. Ocular manifestations include a wide range of intra-ocular inflammation. METHODS: In this study, we report the case of a 52 years-old male patient with syphilitic hemorrhagic necrotizing retinitis. RESULTS: The patient presented to the emergency room for rapid and progressive vision loss and ocular redness lasting three weeks and was under immunosuppressive treatment. The diagnosis was syphilitic hemorrhagic necrotizing retinitis mimicking the typical clinical picture of retinitis caused by Cytomegalovirus infection in immunocompromised patients. CONCLUSIONS: The presented case highlights the need to consider ocular syphilis as a great masquerader even in the presence of atypical presentations such as hemorrhagic retinitis. Syphilis should be tested for treponemal and non-treponemal tests, and it should be ruled out as an etiological agent in every case of new-onset intra-ocular inflammation.

Sarcoid Uveitis: An Intriguing Challenger.

The purpose of our work is to describe the actual knowledge concerning etiopathogenesis, clinical manifestations, diagnostic procedures, complications and therapy of ocular sarcoidosis (OS). The study is based on a recent literature review and on the experience of our tertiary referral center. Data were retrospectively analyzed from the electronic medical records of 235 patients (461 eyes) suffering from a biopsy-proven ocular sarcoidosis. Middle-aged females presenting bilateral ocular involvement are mainly affected; eye involvement at onset is present in one-third of subjects. Uveitis subtype presentation ranges widely among different studies: panuveitis and multiple chorioretinal granulomas, retinal segmental vasculitis, intermediate uveitis and vitreitis, anterior uveitis with granulomatous mutton-fat keratic precipitates, iris nodules, and synechiae are the main ocular features. The most important complications are cataract, glaucoma, cystoid macular edema (CME), and epiretinal membrane. Therapy is based on the disease localization and the severity of systemic or ocular involvement. Local, intravitreal, or systemic steroids are the mainstay of treatment; refractory or partially responsive disease has to be treated with conventional and biologic immunosuppressants. In conclusion, we summarize the current knowledge and assessment of ophthalmological inflammatory manifestations (mainly uveitis) of OS, which permit an early diagnostic assay and a prompt treatment.

Macular Choroidal Thickness: Evaluation of Variability among Measurements and Assessment of Predictive Value of Glaucomatous Visual Field Damage.

INTRODUCTION: This study aimed to investigate the relationship between the choroidal circulation and glaucoma, assessing macular choroidal thickness (MCT) as a predictive value of glaucomatous visual field damage. METHODS: Twenty primary open-angle glaucoma patients were recruited. Patients underwent 2 SS-OCT scans: one with DRI OCT (Topcon) and the other with PLEX Elite 9000 (Zeiss). Standard OCT parameters were acquired by DRI OCT, while MCT was manually measured in 5 points on Plex ELITE 9000 images. The relationship among MCT, standard OCT parameters, and visual field indices was evaluated. Pearson's r correlation was calculated to evaluate these relationships. Reproducibility of measurements was analyzed. RESULTS: MCT measurements showed a good intra- and interobserver repeatability. A negative correlation appeared between MCT and BMI (r = -0.518, p = 0.023). Mean deviation showed a statistically significant correlation with MCT measured at subfoveal and at 1,000 µm nasally (r = 0.50, p = 0.03, and r = 0.52, p = 0.023). A correlation was found between the 2 MCT (Zeiss vs. Topcon) measurements and between MCT and peripapillary choroidal thickness (r = 0.944 and r = 0.740, p < 0.001, respectively). CONCLUSIONS: A good intra- and interobserver reproducibility was found. MCT showed a weak predictive value of glaucomatous visual field damage. A significant correlation was found between MCT and BMI.