A CRMP4-dependent retrograde axon-to-soma death signal in amyotrophic lateral sclerosis.

Amyotrophic lateral sclerosis (ALS) is a fatal non-cell-autonomous neurodegenerative disease characterized by the loss of motor neurons (MNs). Mutations in CRMP4 are associated with ALS in patients, and elevated levels of CRMP4 are suggested to affect MN health in the SOD1G93A -ALS mouse model. However, the mechanism by which CRMP4 mediates toxicity in ALS MNs is poorly understood. Here, by using tissue from human patients with sporadic ALS, MNs derived from C9orf72-mutant patients, and the SOD1G93A -ALS mouse model, we demonstrate that subcellular changes in CRMP4 levels promote MN loss in ALS. First, we show that while expression of CRMP4 protein is increased in cell bodies of ALS-affected MN, CRMP4 levels are decreased in the distal axons. Cellular mislocalization of CRMP4 is caused by increased interaction with the retrograde motor protein, dynein, which mediates CRMP4 transport from distal axons to the soma and thereby promotes MN loss. Blocking the CRMP4-dynein interaction reduces MN loss in human-derived MNs (C9orf72) and in ALS model mice. Thus, we demonstrate a novel CRMP4-dependent retrograde death signal that underlies MN loss in ALS.

Comparison of various treatment modalities in patients with primary vitreoretinal lymphoma: A systematic review and meta-analysis.

BACKGROUND: This systematic review and meta-analysis investigated different treatment modalities' effect on the risk of central nervous system lymphoma progression, ocular disease relapse, systemic lymphoma development and overall survival in primary vitreoretinal lymphoma patients. METHODS: PubMed, EMBASE, Scopus and the Cochrane Library of clinical trials were searched from inception to April 21, 2024. Cohort, cross-sectional and case series studies were included. Methodological quality was assessed using the NIH quality assessment tools. Heterogeneity between studies was assessed using Chi square test and I2 statistic. Outcomes were pooled as odds ratios (OR) using fixed-effects models. Risk of publication bias was assessed using a funnel plot. RESULTS: Included were 28 studies with 476 participants. Ocular treatments included intravitreal methotrexate and/or rituximab injections and ocular radiotherapy. Systemic treatments included intravenous and/or intrathecal chemotherapy, whole-brain radiotherapy and autologous stem cell transplantation. Ocular treatment alone, as compared to systemic or combined treatment, resulted in significantly lower risk of central nervous system lymphoma development (OR = 0.54, p = 0.02) and in no significant difference in the risk for progression to systemic disease (OR = 0.38, p = 0.30) or in overall survival. Significantly lower risk of ocular relapse was found in patients receiving ocular or combined therapy as compared to systemic therapy alone (OR = 0.26, p = 0.001). A subgroup analysis, comparing ocular treatment alone and combined treatment, found no significant difference regarding the risk of central nervous system or systemic lymphoma progression, ocular disease relapse and overall survival. CONCLUSIONS: No benefit was observed for the addition of systemic therapy to ocular treatment in patients with primary vitreoretinal lymphoma.

Online support group for patients with inflammatory eye disease: Characterisation of members and assessment of benefits.

BACKGROUND: Support groups in ophthalmology may be of utmost importance for patients and caregivers. We aimed to characterise members of an online support group for patients and parents of children with inflammatory eye disease and assess the members' expectations and perceived benefits. METHODS: A survey based on a voluntary, anonymous web questionnaire was distributed to the members of the 'Lirot' association online support group. The questionnaire included demographic, ocular and systemic information, functional and psychosocial data, support group use patterns, expectations and perceived benefits. Analysis was done for patients and parents. RESULTS: Out of 67 respondents, 43 (64%) were patients, and 24 (36%) were parents. Fifty-eight (88%) were women. The mean age of respondents was 42.9 ± 1.34 years. Anterior uveitis was the most common, and most patients had good visual acuity (<0.3 logMAR). Parents reported higher anxiety levels (p = 0.044) and a more significant effect of their child's disease on their general function (p = 0.005). Most members sought several experts' opinions, psychological treatments and alternative medicine. All members used the WhatsApp group, while only approximately half used Facebook (p < 0.001). Members' expectations were fulfilled for social support, a sense of shared experience and being able to help others, but not for receiving information (p < 0.001). All members reported being willing to recommend the group to others. CONCLUSIONS: Support group participation benefited group members. We suggest that ophthalmologists encourage their inflammatory eye disease patients to use online support groups, which may significantly improve their well-being.

Pseudophakic cystoid macular oedema and posterior capsular opacification rates after combined phaco-trabeculectomy vs. phaco alone.

PURPOSE: To assess the risk for pseudophakic cystoid macular oedema (PCME) and posterior capsular opacification (PCO) associated with combined cataract surgery and trabeculectomy compared to cataract surgery alone. METHODS: Data analysis of subjects who underwent routine cataract surgery without and with concomitant trabeculectomy at the Department of Ophthalmology, Bristol Eye Hospital, the UK, between January 2008 and December 2017. Odds ratios (ORs) for PCME between the types of surgeries were calculated using univariate and multivariate regression analysis. Multivariate Cox regression controlling for age and gender was used to estimate the hazard ratio (HR) for neodymium-doped yttrium aluminium garnet (Nd:YAG) laser capsulotomies. RESULTS: This study included 56 973 cataract surgeries without and 288 with concomitant trabeculectomy (phaco-trab) with a mean follow-up time of 6.9 ± 4.2 years. Baseline variables (age and gender, diabetes, pseudoexfoliation, use of pupil expansion device and postoperative follow-up time) were comparable between the groups. Postoperative rates of PCME remained non-significant between the cataract surgery and phaco-trabe groups both in uni- and multi-variate analysis (OR 0.347, 95%CI 0.049-2.477, p = 0.291). Furthermore, in Cox regression analysis adjusted for the patients' age and gender, Nd:YAG laser capsulotomy rates remained non-significant between the cataract surgery and phaco-trabe groups (HR 1.250, 95%CI 0.883-1.769, p = 0.209). CONCLUSIONS: In our large cohort study, combining trabeculectomy with cataract surgery did not predispose to an increased PCME or Nd:YAG laser capsulotomy rates.

Retinal vascular occlusions in ocular Behçet disease - a comparative analysis.

PURPOSE: The literature on retinal vascular occlusions in Behçet disease (BD) patients is limited. The aim of this study is to thoroughly investigate retinal vascular occlusions among ocular BD patients. METHODS: Retrospective, multicentre case-control study. Three-hundred and three eyes of 175 patients with ocular BD, from 13 hospitals in Israel and Palestine, were included. Patients were assigned into two groups according to the presence of retinal vascular occlusion. Epidemiology, systemic and ocular manifestations, treatments and outcomes were compared between the groups and risk factors for retinal vascular occlusions were identified. RESULTS: One hundred twenty-five patients (71.4%) were male. The mean age at presentation was 28.2 ± 0.86 years. Retinal vascular occlusions were found in 80 eyes of 54 (30.9%) patients, including branch retinal vein occlusion (51.3%), peripheral vessels occlusions (32.5%), central retinal vein occlusion (13.8%) and arterial occlusions (7.5%). Systemic manifestations were similar among both groups. Anterior uveitis was more common in non-occlusive eyes (p < 0.01). Non-occlusive retinal vasculitis (p = 0.03) and ocular complications were more common in occlusive eyes (p < 0.01). Treatments including mycophenolate mofetil, Infliximab or a combination therapy of anti-metabolite and calcineurin inhibitor were more commonly used by occlusive patients (p < 0.05). Occlusive patients underwent more cataract surgeries (p = 0.03). The occlusive group had worse mean best-corrected visual acuity (BCVA) throughout follow-up (p < 0.01). Risk factors for retinal vascular occlusions included male sex and Jewish ethnicity (p < 0.05). CONCLUSION: Retinal vascular occlusions were found in a third of ocular BD patients. Occlusive eyes had a worse prognosis. Risk factors for vascular occlusions were identified.

Ocular Behçet Disease-Clinical Manifestations, Treatments and Outcomes According to Age at Disease Onset.

Behçet disease (BD) is a multisystemic disease that commonly involves the eyes. Although it affects patients in all age groups, data on ocular disease by age of onset are limited. This retrospective, multicenter study aimed to compare epidemiology, systemic and ocular manifestations, treatments and outcomes between three age groups: juvenile (<18 years), adult (18-39 years) and late (≥40 years) disease onset. The study included 175 ocular BD patients (303 eyes) from Israel and Palestine: juvenile-onset (n = 25, 14.3%), adult-onset (n = 120, 68.6%) and late-onset (n = 30, 17.1%). Most patients in all groups were male. Systemic manifestations were similar in all groups. Systemic co-morbidities were more common in late-onset patients. Bilateral panuveitis was the most common ocular manifestation in all patients. Non-occlusive retinal vasculitis, peripheral vessel occlusions, cataract and elevated intraocular pressure were found more commonly among juvenile-onset eyes. Anterior uveitis and macular ischemia were most common among late-onset eyes, while branch retinal vein occlusion was most common in adult and late-onset eyes. All patients were treated with corticosteroids. Methotrexate, immunomodulatory combinations and biologic treatments were more commonly used for juvenile-onset patients. All groups had a similar visual outcome. Our study showed that patients with ocular BD have varied ocular manifestations and require different treatments according to age of disease onset, but visual outcome is similar.