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Purpose: To evaluate the incidence, clinical features, diagnostic challenges, management and prognosis of cutaneous squamous cell carcinoma of the eyelid (ecSCC) in southern Finland, northern Europe, latitude 62° N. Methods: Patients were identified from the Finnish Cancer Registry and the Helsinki University Hospital databases during a 25‐year period (1998–2022). Age, sex, location, clinical and histopathological diagnosis, treatment and outcome were retrieved. Results: Cutaneous squamous cell carcinoma of the eyelid (ecSCC) was diagnosed in 58 patients. The mean age‐standardized incidence was 1.03 per 100 000. Median age at the time of histopathological diagnosis was 79 (range 55–93) years; sex ratio was 0.52. Clinical diagnosis in the referral was ecSCC in only three patients. The most frequent misdiagnosis (38%) was basal cell carcinoma (BCC). One or more of the known risk factors (smoking, history of extensive sun exposure, systemic immunosuppression and previous in situ cSCC/cSCC) were documented in 71% of the patients. More than one third (38%) of the patients developed in situ SCC elsewhere on the skin; one third (31%) of the patients had invasive cSCC elsewhere. During the median follow‐up time of 24 months, three patients experienced local recurrence, four patients developed metastatic disease (median 19 months) and two patients died of metastatic ecSCC. Conclusion: The estimated incidence of ecSCC in Finland (predominantly white Caucasian) was higher than in a previous study from Europe. Clinical diagnosis of ecSCC is difficult and often misdiagnosed as BCC. Immunosuppression as a risk factor should noticed. Recurrences of ecSCC, which may be lethal, were infrequent. [ABSTRACT FROM AUTHOR]

Purpose: To describe four Finnish families with epithelial recurrent erosion dystrophy (ERED) caused by the pathogenic variant c.3156C>T in collagen type XVII alpha 1 chain gene (COL17A1). Methods: Eleven affected and two unaffected individuals underwent clinical ophthalmological examination, anterior segment photography, and corneal topography. Two of them underwent phototherapeutic keratectomy (PTK). Genetic analysis included both next‐generation and Sanger sequencing. Specimens from the manual keratectomy of one patient were available for ophthalmic pathologic examination, including immunohistochemistry. Results: The common splice‐site altering synonymous variant c.3156C > T, p.(Gly1052=) in COL17A1 was confirmed in 15 individuals with ERED from the four families. Subepithelial corneal scarring grades varied and increased with age, leading to decreased best‐corrected visual acuity. PTK improved vision in 58‐ and 67‐year‐old individuals without reactivating the disease. The keratectomy specimens showed an uneven epithelium and a spectrum of basement membrane abnormalities, including breaks, fragmentation, multiplication and entrapment within the subepithelial scar, reflecting recurrent erosions. The stromal cells consisted of varying proportions of bland and activated fibroblasts and myofibroblasts, reflecting different ages of scars. The family with the largest number of known affected generations originated from Southern Sweden. Conclusion: The phenotype in the Finnish ERED families is consistent with earlier reports of the c.3156C > T variant, although the severity has varied between reports. The phenotype may be modulated by other genes. This study suggests a likely founder effect of the variant in both Finnish and Swedish populations due to their shared population histories. If vision is compromised, PTK can be considered especially in older patients. [ABSTRACT FROM AUTHOR]

Retinitis pigmentosa (RP) is a group of inherited degenerative retinal disorders affecting more than 1.5 million people worldwide. For 30-50% of individuals with RP, the genetic cause remains unresolved by current clinical diagnostic gene panels. It is likely explained by variants in novel RP-associated genes or noncoding regulatory regions, or by complex genetic alterations such as large structural variants. Recent developments in long-read sequencing techniques have opened an opportunity for efficient analysis of complex genetic variants. We analysed a Finnish family with dominantly inherited RP affecting six individuals in three generations. Two affected individuals underwent a comprehensive clinical examination in combination with a clinical diagnostic gene panel, followed by whole exome sequencing in our laboratory. They exhibited typical signs of RP, yet initial sequence analysis found no causative variants. Reanalysis of the sequencing data detected a LINE-1 (L1) retrotransposon insertion of unknown size in exon 4 of the RP1 axonemal microtubule-associated (RP1) gene. The large chimeric L1 insertion that segregated with the disease was further characterised using targeted adaptive nanopore sequencing of RP1, allowing us to identify a 5.6 kb L1 transposable element insertion in RP1 as the cause of RP in this family with dominantly inherited RP. [ABSTRACT FROM AUTHOR]

Purpose Methods Results Conclusions To report national practices and recent progress in competency‐based medical education (CBME) implementation in ophthalmology across European countries.A 30‐question online survey was emailed to European Union of Medical Specialists (UEMS) ophthalmology section delegates, European Board of Ophthalmology Diploma (EBOD) examiners and presidents of ophthalmology societies affiliated with UEMS/EBO.A total of 230 ophthalmologists with an average age of 54.7 years [30–77] and from 28 countries completed the survey. Half of them had been involved as medical educators for more than 10 years. The majority (74%) exercised their educational role in a University Hospital. Ninety six percent of them dedicated less than 50% of their activity to teaching. A third dedicated more than a half of their activity to patient care. The teaching of skills reported (medical, surgical, research, attitudinal and theoretical knowledge) was significantly better applied than their assessment. While 91% of the respondents found it necessary to harmonize European Training Requirements (ETR) in ophthalmology, competency‐based education concepts were rarely implemented in their country (for instance, 8% for CBME; 6% for entrustable professional activities (EPAs) and 3% for ETR).Despite considerable diversity in European residency programmes, post‐graduate medical education leaders in ophthalmology agree on the need to find a platform for equivalence in the content of the basic training requirements that constitute the professional identity of a practicing ophthalmologist. [ABSTRACT FROM AUTHOR]

Purpose Methods Results Conclusion To describe clinical characteristics in Finnish patients with X‐linked retinoschisis (XLRS) longitudinally with emphasis on retinal morphology and genotype–phenotype correlations.A retrospective cohort study reviewed medical records from patients with genetically confirmed XLRS from the Department of Ophthalmology, Helsinki University Hospital. Best‐corrected visual acuity (BCVA), refraction, colour fundus photography, spectral‐domain optical coherence tomography and genetic information were collected.Fifty‐two males were diagnosed at the median age of 7 years (range 1–57) and followed for a median of 8 years (range, 1–49). Baseline findings included macular retinoschisis in 92 (89%), macular atrophy in 25 (24%) and peripheral retinoschisis in 22 (21%) eyes. Vitreous haemorrhage occurred in 10 (10%) eyes, more frequently with peripheral schisis (p < 0.001). Nearly half of the patients, 22 (42%) were classified as visually impaired according to WHO. Median central retinal thickness was similar between initial (355 μm) and latest visits (360 μm) (p = 0.781). Low BCVA was associated with macular atrophy (p < 0.001), ellipsoid zone disruption (p = 0.007) and peripheral retinoschisis (p = 0.006). The three Finnish founder mutations c.214G >A, c.221G >T, and c.325G >C in exon 4 of retinoschisin 1 (RS1) were identified in 40 patients (77%). No associations were found between the genotypes and phenotypes.Three‐fourths of the patients carried the Finnish founder mutations in RS1, but we did not detect any genotype–phenotype association. Macular atrophy was associated with the poorest visual acuity. Ocular compilations were associated with peripheral retinoschisis, suggesting that these patients should be followed more frequently. [ABSTRACT FROM AUTHOR]

ABSTRACT Uveal melanoma (UM) is a rare yet aggressive eye cancer causing over 50% mortality from metastasis. Familial UM, amounting to 1%–6% of patients in Finland and the United States, mostly lack identified genetic cause, while 8% show associations with other cancer syndromes. We searched novel genetic associations for predisposition to UM, additional to already studied BAP1 and MBD4, by using targeted amplicon sequencing of 19 genes associated with UM, BAP1, or renal cell carcinoma in 270 consecutively enrolled Finnish patients with UM. Key UM drivers GNAQ, GNA11, CYSLTR2, PLCB4, EIF1AX, and SF3B1 lacked pathogenic germline variants. One patient carried the pathogenic BRCA1 variant c.3626del p.(Leu1209*), and one harbored a novel truncating MET variant c.252C > G p.(Tyr84*), classified as likely pathogenic. FLCN and BRCA2, previously identified with pathogenic variants in patients with UM, did not have such variants in our cohort. Two patients were heterozygous for a pathogenic recessive BLM variant c.2824‐2A > T. None of the carriers of identified variants had familial UM. We identified BRCA1 and MET as genes with pathogenic germline variants in Finnish UM patients, each with a frequency of 0.4% (95% confidence interval, 0–2). [ABSTRACT FROM AUTHOR]

Purpose: To analyze central corneal in vivo confocal microscopy (IVCM) in Terrien marginal degeneration (TMD)., Methods: An observational prospective case-control study. Ten Finnish patients with TMD from a tertiary referral center were compared with 10 age- and sex-matched healthy volunteers. Seven patients had bilateral TMD. Age, anterior segment optical coherence tomography, extent of thinning in clock hours, grade of microdots, and stage of TMD were analyzed., Results: According to Süveges and Wang classification, the median stage of TMD was 2 (range, 2-3) and 2 (range, 2-6), respectively. Twelve (71%) of 17 eyes with clinical TMD showed corneal thinning at all clock hours. The median age at the time of examination was 70 years (range, 28-81), and the median time from diagnosis 8.8 years (range, 6.0-15.2). By IVCM, the epithelium, subepithelial nerve plexus, and endothelium were intact in all eyes. The anterior stroma showed bilateral hyperreflective dots in the central cornea beneath the subepithelial nerve plexus in all eyes, and larger patches were detected in the posterior stroma anterior to Descemet membrane; both were invisible by anterior segment optical coherence tomography. As compared with controls, the grade of anterior microdots increased faster with age before the age of 65, and that of posterior stromal patches was higher. Two patients additionally had bilateral hyperreflective needle-like deposits in the anterior and midstroma., Conclusions: By IVCM, TMD is characterized regardless of clinical laterality by bilateral microdots in the central corneal stroma. They might be a supporting diagnostic criterion and alone could suggest subclinical disease., Competing Interests: M. Ruutila and T. T. Kivelä report personal fees from Santen Finland outside the submitted work. J. A. Turunen received lecture fees from Thea Finland and Santen Finland outside the submitted work. The remaining authors have no funding or conflicts of interest to disclose., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: To explore the genetic background of choroidal and ciliary body melanoma among children and young adults, with special focus on BAP1 germline variants in this age group., Methods: Patients under the age of 25 and with confirmed choroidal or ciliary body melanoma were included in this retrospective, multicenter observational study. Nuclear BAP1 immunopositivity was used to evaluate the presence of functional BAP1 in the tumor. Next-generation sequencing using Ion Torrent platform was used to determine pathogenic variants of BAP1, EIF1AX, SF3B1, GNAQ and GNA11 and chromosome 3 status in the tumor or in DNA extracted from blood or saliva. Survival was analyzed using Kaplan-Meier estimates., Results: The mean age at diagnosis was 17 years (range 5.0-24.8). A germline BAP1 pathogenic variant was identified in an 18-year-old patient, and a somatic variant, based mainly on immunohistochemistry, in 13 (42%) of 31 available specimens. One tumor had a somatic SF3B1 pathogenic variant. Disomy 3 and the absence of a BAP1 pathogenic variant in the tumor predicted the longest metastasis-free survival. Males showed longer metastasis-free survival than females (P = 0.018)., Conclusions: We did not find a stronger-than-average BAP1 germline predisposition for choroidal and ciliary body melanoma among children and young adults compared to adults. Males had a more favorable survival and disomy 3, and the absence of a BAP1 mutation in the tumor tissue predicted the most favorable metastasis-free survival. A BAP1 germline pathogenic variant was identified in one patient (1%), and a somatic variant based mainly on immunohistochemistry in 13 (42%).