Plaque brachytherapy is an effective eye and vision-sparing method to treat patients with intraocular tumors. Practitioners are encouraged to use ABS-OOTF guidelines to enhance their practice.

The frequency of BAP1 germline pathogenic variants in consecutive Finnish patients with uveal melanoma who come from a high-risk region for the development of this cancer is comparable with reports from other populations.

ABSTRACT.Purpose: To report a case of delayed fungal endophthalmitis by Paecilomyces variotii following uncomplicated cataract surgery. To our knowledge this is the first reported case of postoperative endophthalmitis by this species. Methods: We report the longterm clinical follow-up of an 83-year-old female who underwent uncomplicated sutureless, small-incision cataract surgery. She developed recurring uveitis 4 months after surgery. Vitreous tap and finally complete vitrectomy with removal of the capsular bag including the intraocular lens were performed. Fungi were studied by histopathology and culture. Results: At histopathological examination, the fungi were found to be closely related with the capsular bag. A few mononuclear inflammatory cells were encountered. At culture, Paecilomyces variotii, a common ubiquitous non-pathogenic saprophyte, was identified. Despite systemic, intravitreal and topical antifungal therapy after vitrectomy the uveitis recurred several times, but no fungal organisms were isolated from the repeat intraocular specimen. At 18 months postoperatively the subject's visual acuity was finger counting at 2 metres. At the time of surgery the operating room air-conditioning system was undergoing repairs. Cases of fungal endophthalmitis after contamination from air-conditioning ventilation systems have been reported before, but none of the cases reported have been caused by P. variotii. Conclusion: P. variotii, a non-pathogenic environmental saprophyte, may be disastrous if introduced into the eye. International recommendations on the environmental control of the operating room air-conditioning ventilation system should be strictly followed. No intraoperative surgery should be undertaken while the air-conditioning system is undergoing repairs or service.

Pathogenic germline variants in the BRCA1-associated protein 1 (BAP1) gene cause the BAP1 tumor predisposition syndrome (BAP1-TPDS) with increased risk of several cancers, the most frequent of which is uveal melanoma (UM). Pathogenicity of loss-of-function (LOF) BAP1 variants is clear, as opposed to that of missense and regulatory region variants. We sequenced the coding, promoter, untranslated region (UTR) and intronic regions of BAP1 and analyzed copy number variations (CNVs). In this nationwide study, the cohort comprised UM patients diagnosed between 2010 and 2017. These included 432 of 520 consecutive Finnish UM patients, 16 of whom were familial, and one additional patient from a Finnish–Swedish family. Twenty-one different rare variants were found: seven exonic, seven intronic, four 3′ UTR and three promoter. We considered five variants likely to be pathogenic by effect on splicing, nuclear localization or deubiquitination activity. Intron 2 (c.67+1G>T) and exon 14 (c.1780_1781insT) LOF variants were presumed founder mutations, occurring in two and four families, respectively; both abolished nuclear localization in vitro. Intron 2, exons 5 (c.281A>G) and 9 (c.680G>A) missense variants markedly reduced deubiquitinating activity. A deep intronic 25 base pair deletion in intron 1 caused aberrant splicing in vitro. On the basis of functional studies and family cancer history, we classified four exon 13 missense variants as benign. No CNVs were found. The prevalence of pathogenic variants was 9/433 (2%) and 4/16 (25%) in Finnish UM families. Family cancer history and functional assays are indispensable when establishing the pathogenicity of BAP1 variants. Deep intronic variants can cause BAP1-TPDS.