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.

Update on the systemic management of noninfectious uveitis in children and adolescents.

Noninfectious uveitis (NIU) in children and adolescents is a rare but treatable cause of visual impairment in children. Treatments for pediatric NIU and their side effects, along with the risks of vision loss and the need for long-term disease monitoring, pose significant challenges for young patients and their families. Treatment includes local and systemic approaches and this review will focus on systemic therapies that encompass corticosteroids, conventional synthetic disease-modifying antirheumatic drugs (csDMARD), and biological disease-modifying antirheumatic drugs (bDMARD). Treatment is generally planned in a stepwise approach. Methotrexate is well-established as the preferential csDMARD in pediatric NIU. Adalimumab, an antitumor necrosis factor (TNF) agent, is the only bDMARD formally approved for pediatric NIU and has a good safety and efficacy profile. Biosimilars are gaining increasing visibility in the treatment of pediatric NIU. Other bDMARD with some evidence in literature for the treatment of pediatric NIU include infliximab, tocilizumab, abatacept, rituximab and, more recently, Janus kinase inhibitors. Important aspects of managing children on these systemic therapies include vaccination issues, risk of infection, and psychological distress. Also, strategies need to address regarding primary nonresponse/secondary loss of response to anti-TNF treatment, biological switching, and monitoring regimens for these drugs. Optimal management of pediatric uveitis involves a multidisciplinary team, including specialist pediatric uveitis and rheumatology nurses, pediatric rheumatologists, psychological support, orthoptic and optometry support, and play specialists.

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.

Acute-Onset Retinal Conditions Mimicking Acute Optic Neuritis: Overview and Differential Diagnosis.

Acute optic neuritis (AON) is a common cause of sudden visual loss in young patients. Because of the risk of demyelinating disease, patients affected by unilateral or bilateral optic neuritis should be evaluated and treated accordingly. Despite advancements in imaging of the brain and retina, misdiagnosis of AON is not uncommon. Indeed, some acute disorders of the retina have the potential to mimic AON and their prompt diagnosis may avoid unnecessary neurologic investigation, psychological stress to the patient, and delays in treatment. This review describes uncommon retinal disorders presenting with sudden-onset visual loss and absent or subtle funduscopic manifestation that can mimic AON. Multimodal retinal imaging is essential in detecting these conditions and in their differential diagnosis. It behooves neurologists and general ophthalmologists to be aware of these entities and be familiar with multimodal imaging of the retina.

Paracentral Acute Middle Maculopathy in A Young Girl Treated with Interferon-Beta for Nasopharyngeal Carcinoma.

PURPOSE: To describe a case of interferon-beta retinopathy associated with paracentral acute middle maculopathy. CASE REPORT: A 15-year-old girl with Epstein-Barr virus-positive advanced nasopharyngeal carcinoma WAS REFERRED with reduced visual acuity. Multimodal imaging findings, including optical coherence tomography angiography, at presentation and evolution following cessation of interferon therapy are presented. CONCLUSION: The presentation of paracentral acute middle maculopathy in this patient supports the presumed ischaemic pathogenesis in interferon retinopathy. The imaging findings provide evidence of deep capillary plexus involvement in interferon retinopathy with evolution to permanent structural damage within the inner nuclear layer.

Knowledge, Attitudes, Perceptions and Vaccination Acceptance/Hesitancy among the Community Pharmacists of Palermo's Province, Italy: From Influenza to COVID-19.

In Italy, following the start of the SARS-CoV-2 vaccination campaign, community pharmacies (CPs) were recruited on a voluntary basis in order to administer COVID-19 vaccines as part of their activities. The aim of the present study was to investigate the knowledge, attitudes, and practices regarding SARS-CoV-2 infection prevention, and vaccine acceptance/hesitancy towards COVID-19 and influenza vaccinations among the community pharmacists operating in the Palermo Province. A cross-sectional study was conducted, with two different questionnaires administered before and after the conduction of the vaccination campaign against SARS-CoV-2 at the COVID-19 vaccination center of the Palermo University Hospital (PUH). The baseline survey showed that 64% of community pharmacists (CPs) declared that they planned to vaccinate against SARS-CoV-2, and 58% were vaccinated against influenza during the 2020/2021 season. Factors significantly associated with willingness to receive the COVID-19 vaccination were confidence in vaccines (adjOR 1.76; CI 1.11-2.80), fear of contracting SARS-CoV-2 infection (adjOR 1.50; CI 1.06-2.11), considering COVID-19 vaccination to be the best strategy to counteract SARS-CoV-2 (adjOR 1.79; CI 1.39-2.29), and adherence to influenza vaccination during the 2020/2021 season (adjOR 3.25; CI 2.23-4.25). The adherence among CPs of the Palermo Province to COVID-19 vaccination was 96.5%. From the post-vaccination survey, the main reasons for changing opinions on vaccination adherence were the introduction of mandatory vaccinations, fear of contracting COVID-19, and limitations on work activities in the case of vaccine refusal. The achievement of very high COVID-19 vaccination coverage rates among healthcare professionals (HCPs) in the present study was mainly due to the mandatory vaccination policies; nevertheless, a willingness for COVID-19 vaccination was relatively high among pharmacists before the beginning of the vaccination campaign. HCPs and CPs should receive training on vaccination, which is recommended in the national immunization plan and is also suggested by the respondents in our study, in order to routinely re-evaluate their own vaccination profiles, as well as those of their patients.

A case of Vogt-Koyanagi-Harada-like uveitis secondary to dabrafenib/trametinib therapy for advanced melanoma.

We report a case of ocular drug toxicity consistent with bilateral Vogt-Koyanagi-Harada (VKH) like disease in a patient with cutaneous melanoma treated with Dabrafenib/Trametinib therapy. A 53-year-old man with a history of metastatic cutaneous melanoma, treated with Dabrafenib/Trametinib, developed a severe acute panuveitis with granulomatous anterior uveitis and multiple serous retinal detachments. The ocular inflammatory reaction was classified as a bilateral Vogt-Koyanagi-Harada disease. Intraocular inflammation resolved after discontinuation of chemotherapeutic agents and aggressive topical and systemic corticosteroid therapy. The present case outlines the importance of recognizing VKH-like syndrome as a possible consequence of therapy with dabrafenib and trametinib.

MULTIMODAL IMAGING AND TREATMENT OF SYPHILITIC CHOROIDAL NEOVASCULARIZATION.

PURPOSE: To report a rare case of choroidal neovascularization (CNV) developed 2 years after successful treatment of ocular syphilis, identified by optical coherence tomography angiography. METHODS: Case report. RESULTS: A 31-year-old man with a history of syphilitic chorioretinitis developed a CNV 2 years after clinical remission of the infection. Structural optical coherence tomography (OCT) and optical coherence tomography angiography were helpful in providing detailed evidence of an extrafoveal CNV in an easy and noninvasive way. In comparison, the identification of CNV on fluorescein angiography was difficult because of the retinal blood barrier breakdown and intense choroidal background fluorescence for diffuse chorioretinal scarring of syphilitic chorioretinitis. The patient underwent 3 intravitreal injections of anti-vascular endothelial growth factor in addition to 25 mg/day of oral prednisone, with the restoration of previous visual acuity. CONCLUSION: Choroidal neovascularization is a rare, but sight-threatening complication of syphilitic chorioretinitis. The combination of different imaging modalities, and in particular optical coherence tomography angiography, allowed reaching a definite diagnosis of CNV. Combined treatment of systemic steroid and intravitreal anti-vascular endothelial growth factor was effective in controlling the CNV and improving the visual outcome.

The identification of activity of choroidal neovascularization complicating angioid streaks.

OBJECTIVES: To inspect the inter-reader agreement of different diagnostic modalities in identifying choroidal neovascularization (CNV) activity secondary to angioid streaks (AS) and to analyze the prevalence of subretinal hyper-reflective material (SHRM) in active CNV. METHODS: Retrospective study of patients with AS with active CNV; optical coherence tomography (OCT), OCT angiography (OCTA), fundus fluorescein angiography (FFA), and indocyanine green angiography (ICGA) from each patient were collected. Agreement between two readers using different diagnostic modalities is presented as free-marginal kappa (k) and 95% confidence interval (CI). RESULTS: This study included 19 eyes of 12 patients with active CNV (5 naive and 14 previously treated). Agreement among readers on CNV activity was excellent for OCT (k =0.88; 95% CI 0.71-1.00), good for FFA (k = 0.70; 95% CI 0.46-0.94) and ICGA (k = 0.58; 95% CI 0.31-0.84), and poor using OCTA (k = 0.39; 95% CI 0.11-0.68). SHRM was the most common OCT finding associated with active CNV (100%); fuzzy borders were present in 53% of SHRM cases at baseline. CONCLUSIONS: Identification of CNV activity in AS is challenging; OCT was the best modality to inspect active CNV. The identification of SHRM contributed to recognizing active CNV. Further studies are needed to assess the role of SHRM in anticipating prognosis and guiding treatment of CNV secondary to AS.

Intravitreal aflibercept for management of choroidal neovascularization secondary to angioid streaks : The Italian EYLEA-STRIE study.

PURPOSE: To investigate the effect and the safety of intravitreal aflibercept in patients affected by choroidal neovascularization secondary to angioid streaks with a long-term follow-up. METHODS: Multicentre, open-label, phase IIb study (EYLEA-STRIE, EudraCT Number 2014-000986-30) involving four Italian centres (IRCCS Ospedale San Raffaele (Milano), Fondazione G.B. Bietti (Roma), Policlinico (Milano), Ospedale Luigi Sacco (Milano)). Patients with active choroidal neovascularization secondary to angioid streaks with foveal involvement were prospectively enrolled and followed for 18 months. All the patients received intravitreal 2 mg/0.05 mL aflibercept at the time of enrolment, followed by a pro-re-nata regimen for 48 weeks. Best-corrected visual acuity and central macular thickness were measured monthly. Adverse events were monitored at each visit. RESULTS: Twenty-three eyes of 20 patients were analysed. Mean number of injections per patient was 4.30 ± 1.2. At week 48, the best-corrected visual acuity was 0.42 ± 0.40 LogMAR (p = 0.6 from baseline) and 18 eyes (81.8%) featured stability within 15 letters. The central macular thickness significantly reduced (p = 0.03). Eleven ocular non-serious adverse events and two serious adverse events were observed (one case of endophthalmitis and one case of acute gastritis were reported). CONCLUSION: Intravitreal aflibercept represents a valid option for the management of choroidal neovascularization complicating angioid streaks. Further studies with longer follow-up and different therapeutic regimens are warranted to ascertain the best control of the disease.

Features of Retinitis-like Lesions in Vitreoretinal Lymphoma.

Purpose: To describe the distinguishing features of retinitis-like lesions seen in vitreoretinal lymphoma (VRL) from viral and toxoplasma retinitis.Methods: In this multicenter, retrospective study, we reviewed charts and imaging of consecutive patients with VRL. The associated features and the characteristics of retinitis-like lesions were assessed and compared with those of viral and toxoplasmic retinochoroiditis. Primary outcome measures were the unique features of VRL retinitis-like lesions.Results: Out of 76 eyes of 38 patients with VRL, retinitis-like lesions were identified in 6 eyes and confirmed on OCT. Distinctive features of VRL retinitis-like lesions were massive retinal thickening, associated sub-retinal pigment epithelium infiltrates and partial restoration of retinal layers after specific therapy.Conclusion: VRL can present with retinitis-like lesions that have distinctive OCT features on presentation as well as healing that can help to differentiate them from other lookalike etiologies and can guide further diagnostic and therapeutic interventions.

Severe Hypotony Maculopathy in Anterior Uveitis Associated with Hodgkin Lymphoma.

Purpose: To describe the clinical course and management of anterior uveitis complicated by ocular hypotony associated with Hodgkin lymphoma.Design: Case report.Methods: Chart and multimodal imaging review, including ultrasound biomicroscopy, widefield fundus pictures, fundus autofluorescence, fluorescein angiography, and indocyanine green angiography.Results: A 44-year-old female with progressive visual deterioration and history of low-grade fever developed bilateral granulomatous anterior uveitis complicated by severe hypotony maculopathy, not improving with systemic and topical steroids. After starting ibopamine 2% eye drops, ocular hypotony progressively resolved with visual recovery. Histologic examination of a biopsied enlarged lymph node of the neck revealed the presence of Hodgkin lymphoma, for which the patient underwent systemic chemotherapy.Conclusion: Severe hypotony maculopathy complicating anterior uveitis can be associated with Hodgkin lymphoma. Topical ipobamine 2% was safe and effective in the treatment of ocular hypotony in this case.

The "Sponge sign": A novel feature of inflammatory choroidal neovascularization.

INTRODUCTION: To investigate choroidal thickness changes related to the clinical activity of inflammatory choroidal neovascularization in punctate inner choroidopathy/multifocal choroiditis as compared to myopic choroidal neovascularization. MATERIALS AND METHODS: Consecutive inflammatory choroidal neovascularization secondary to punctate inner choroidopathy/multifocal choroiditis, and myopic choroidal neovascularization were retrospectively reviewed. By means of enhanced-depth imaging optical coherence tomography, choroidal thickness was assessed at the same location before choroidal neovascularization development, at choroidal neovascularization onset (baseline), and after treatment. RESULTS: Eleven eyes with inflammatory choroidal neovascularization and 11 eyes with myopic choroidal neovascularization were analyzed. Choroidal thickness beneath inflammatory choroidal neovascularization significantly increased at baseline and decreased after therapy ("Sponge sign"), reaching preclinical values. In particular, mean choroidal thickness under inflammatory choroidal neovascularization was 145 ± 85 µm at the preclinical stage, increased to 210 ± 103 µm at baseline (p = 0.006), and decreased to 136 ± 87 µm after treatment (p = 0.017). Conversely, no significant choroidal thickness changes were disclosed in myopic choroidal neovascularization eyes, under any location. CONCLUSION: Optical coherence tomography-based choroidal thickness evaluation may represent an additional useful tool to monitor inflammatory choroidal neovascularization activity. Moreover, choroidal thickness under choroidal neovascularizations could be used to discriminate the origin of choroidal neovascular membrane, either inflammatory or myopic, in doubtful cases and guide the therapeutic management.

Clinical Experience in a Large Cohort of Patients with Vitreoretinal Lymphoma in a Single Center.

Background/aims: To report our five-year experience on vitreoretinal lymphoma (VRL) as a single-center tertiary hospital. Methods: The ophthalmic, cytopathology, and onco-hematologic records of patients with VRL consecutively seen from 2014 to 2019 were reviewed. Results: Fifty-nine eyes of 31 patients with large B-cell VRL were included. Eighty-one percent has developed central nervous system lymphoma at the end of follow-up. Several different imaging findings were noted, including vitritis, leopard spot appearance, Bruch's membrane/RPE infiltrations, and ellipsoid zone disruption. A variable combination of MYD88-L265P mutation in the aqueous and/or in the vitreous and positive cytology/histology allowed to reach a definite diagnosis in all the patients. Therapies included intravitreal injections of methotrexate and rituximab, systemic chemotherapy, pan-encephalic radiotherapy, and hematopoietic stem cell transplantation. Conclusion: No definite guidelines exist for VRL management. It is crucial to collect as much data as possible from tertiary referral hospitals, which suitably manage a conspicuous number of VRL patients.

Management of Juvenile idiopathic arthritis-associated uveitis duringthe COVID-19 pandemic in a pediatric referral center in Lombardy.

Italy was the first European country to be affected by the SARS-CoV-2 pandemic. In this scenario, we had to face a new clinical approach in our Pediatric Rheumatology Unit for the management of patients affected by juvenile idiopathic arthritis (JIA)-associated uveitis. During the lockdown (phase 1), the weekly outpatient clinic was discontinued and telephone consultations were set up. A toll-free telephone number was instituted for emergencies. None of our children with JIA-associated uveitis was advised to stop the ongoing immunosuppressant systemic therapy. We had no cases of COVID-19 infection and uveitis activity was under control in all but two out of 125 patients, which was comparable with the pre-COVID-19 situation. During phase 2 of the pandemic, hospital and ambulatory rearrangements were made to minimize the risk of SARS-CoV-2 infection. Overall, during the first 4 weeks of phase 2, we did not notice an increased number of patients with uveitis activity.

Choroidal involvement in Rosai-Dorfman disease successfully treated with cobimetinib.

Rosai- Dorfman disease (RDD) is a rare systemic pseudo-lymphomatous disorder with unknown etiology. No guidelines exist regarding its management and treatment when the disease is progressing. Choroidal involvement in RDD has rarely been reported and has often been misdiagnosed. We describe a case of a 64-year-old male diagnosed with RDD by means of choroidal biopsy, successfully treated with a MEK inhibitor, namely Cobimetinib, and its follow-up over 5 years, with good final anatomical and functional results. This is the first reported case of RDD diagnosed with an intraocular biopsy performed on a non-enucleated globe, thus preserving the integrity and function of the eye. This case emphasizes the need for a choroidal biopsy when the diagnosis is not straightforward and the starting of targeted therapy to retain a good visual function.

Macular optical coherence tomography findings after vitreoretinal surgery for rhegmatogenous retinal detachment.

The primary aim of this study was to summarize and illustrate the main structural cross-sectional optical coherence tomography findings encountered after vitreoretinal surgery for rhegmatogenous retinal detachment. This was a non-systematic review of literature on structural cross-sectional optical coherence tomography findings after vitreoretinal surgery for rhegmatogenous retinal detachment. Adequate illustrations of the main findings described were found after a retrospective analysis of imaging and charts of patients operated at the department where this study was performed. The main structural cross-sectional optical coherence tomography findings after vitreoretinal surgery for rhegmatogenous retinal detachment included persistent subretinal fluid, subretinal blebs, retinal folds, subretinal perfluorocarbon liquids, macular alterations related to silicone oil, epiretinal membranes, proliferative vitreoretinopathy, cystoid macular edema, macular holes, and recurrent retinal detachment. In conclusion, optical coherence tomography was a useful tool after vitreoretinal surgery for rhegmatogenous retinal detachment. Some optical coherence tomography findings may not be evident on fundus examination, and optical coherence tomography can reveal essential details for the clinical management and the visual prognosis. Other findings, despite being visible on funduscopic examination, may be better assessed with the aid of optical coherence tomography. All these elements contribute to support the importance of tomographic assessment in the follow-up of eyes treated for vitreoretinal conditions.