Best Disease: Global Mutations Review, Genotype-Phenotype Correlation, and Prevalence Analysis in the Israeli Population.

Purpose: To review all reported disease-causing mutations in BEST1, perform genotype-phenotype correlation, and estimate disease prevalence in the Israeli population. Methods: Medical records of patients diagnosed with Best disease and allied diseases from nine Israeli medical centers over the past 20 years were collected, as were clinical data including ocular findings, electrophysiology results, and retina imaging. Mutation detection involved mainly whole exome sequencing and candidate gene analysis. Demographic data were obtained from the Israeli Bureau of Statistics (January 2023). A bibliometric study was also conducted to gather mutation data from online sources. Results: A total of 134 patients were clinically diagnosed with Best disease and related conditions. The estimated prevalence of Best disease was calculated to be 1 in 127,000, with higher rates among Arab Muslims (1 in 76,000) than Jews (1 in 145,000). Genetic causes were identified in 76 individuals (57%), primarily showing autosomal-dominant inheritance due to BEST1 mutations (58 patients). Critical conserved domains were identified consisting of a high percentage of dominant missense mutations, primarily in transmembrane domains and the intracellular region (Ca2+ binding domain) of the BEST1 protein. Conclusions: This study represents the largest cohort of patients with Best disease reported in Israel and globally. The prevalence in Israel is akin to that in Denmark but is lower than that in the United States. Critical conserved domains within the BEST1 protein are pivotal for normal functioning, and even minor missense alterations in these areas lead to a dominant disease manifestation. Genetic testing is indispensable as the gold standard for Best disease diagnosis due to the variable clinical presentation of the disease.

Endogenous fungal endophthalmitis: risk factors, clinical course, and visual outcome in 13 patients.

AIM: To analyze the risk factors, ophthalmological features, treatment modalities and their effect on the visual outcome in patients with endogenous fungal endophthalmitis (EFE). METHODS: Data retrieved from the medical files included age at presentation to the uveitis clinic, gender, ocular symptoms and their duration before presentation, history of fever, eye affected, anatomical diagnosis and laboratory evidence of fungal infection. Medical therapy recorded included systemic antifungal therapy and its duration, use of intravitreal antifungal agents and use of oral/intravitreal steroids. Surgical procedures and the data of ophthalmologic examination at presentation and at last follow-up were also collected. RESULTS: Included were 13 patients (20 eyes, mean age 58y). Ten patients presented after gastrointestinal or urological interventions and two presented after organ transplantation. In one patient, there was no history of previous intervention. Diagnostic vitrectomy was performed in 16 eyes (80%) and vitreous cultures were positive in 10 of the vitrectomized eyes (62.5%). In only 4 patients (31%), blood cultures were positive. All patients received systemic antifungal therapy. Sixteen eyes (80%) received intravitreal antifungal agent with voriconazole being the most commonly used. Visual acuity (VA) improved from 0.9±0.9 at initial exam to 0.5±0.8 logMAR at last follow-up (P=0.03). A trend of greater visual improvement was noted in favor of eyes treated with oral steroids (±intravitreal dexamethasone) than eyes that were not treated with steroids. The most common complication was maculopathy. Twelve eyes (60%) showed no ocular complications. CONCLUSION: High index of suspicion in patients with inciting risk factors is essential because of the low yield of blood cultures and the good general condition of patients at presentation. Visual prognosis is improved with the prompt institution of systemic and intravitreal pharmacotherapy and the immediate surgical intervention. Oral±local steroids could be considered in cases of prolonged or marked inflammatory responses in order to hasten control of inflammation and limit ocular complications.

Uveitis Induced by Biological Agents Used in Cancer Therapy.

Purpose: To report cases of uveitis induced by biological therapy given for cancer.Methods: Retrospective review of medical charts of patients.Results: Included were six patients aged 14-81 years. Three were treated with vemurafenib and one each with nivolumab, ipilimumab, and osimertinib. The oncological diagnoses were metastatic thyroid carcinoma, pleomorphic xanthoastrocytoma, metastatic melanoma, adenocarcinoma of the lung, and metastatic breast cancer. Ocular manifestations appeared 4-82 weeks after the biological treatment was initiated. The most common ocular presentation was anterior uveitis. Onset was sudden in all cases. The median duration of uveitis was 70 weeks. Treatment included topical or systemic corticosteroids; one patient received a single intravitreal steroid injection in one eye.Conclusions: Uveitis may rarely be induced by treatment with biological agents for cancer. Both oncologists and ophthalmologists should be aware of this potential side effect. Early detection and management can prevent permanent complications and save the patient's vision.