Search

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]

Purpose: To identify germline variants in myocilin (MYOC) and other known monogenic glaucoma genes in Finnish patients with juvenile open‐angle glaucoma (JOAG). Methods: Finnish patients with JOAG treated between 2010 and 2018 at the Department of Ophthalmology, Helsinki University Hospital, Finland, were enrolled. We sequenced all exonic regions and flanking splice sites of MYOC for five patients and one healthy relative using Sanger sequencing. In 48 patients, we performed exome sequencing to identify variants also in 28 other glaucoma‐related genes. Results: Fifty‐three individuals with JOAG from 50 pedigrees, and one healthy relative, participated. The mean age at diagnosis was 30.8 years [SD 7.6; range 11 to 39]. Five probands had probably pathogenic variants in MYOC: c.1102C>T p.(Gln368Ter), c.1109C>T p.(Pro370Leu), c.1130C>T p.(Thr377Met), c.1132G>A p.(Asp378Asn) and c.1456C>T p.(Leu486Phe). Four of these patients had a family history of dominantly inherited JOAG. The frequency of MYOC variants was 10% (5 of 50 families). One patient and his mother with JOAG had a novel loss‐of‐function variant in the FOXC1 gene, c.366G>A p.(Trp122Ter). A patient with sporadic JOAG had a homozygous likely pathogenic variant in the LTBP2 gene, c.3938G>A p.(Cys1313Tyr). The genetic variants explained 14% (7 out of 50 families; 95% CI, 6%–23%) of JOAG in our cohort. Conclusions: The frequency of pathogenic variants in previously known glaucoma‐associated genes is low in Finnish patients with JOAG. Because of the distinct genetic background of Finns, it might be possible to identify novel glaucoma genes through our JOAG series in the future. [ABSTRACT FROM AUTHOR]

Purpose: To compare intraocular pressure (IOP) and pain after a single versus split bolus of intravenous hypertonic saline (IVHTS). Methods: In a prospective, randomized, interventional trial, we enrolled patients with an IOP of 22–34 mmHg. Twenty patients in Group 1 received IVHTS as a single bolus of 1 mmol/kg 23.4% sodium chloride, and 13 patients in Group 2 received two boli of 0.5 mmol/kg separated by 10 min. They graded pain at the infusion site. We measured IOP, heart rate and blood pressure before and 10 and 20 min after IVHTS. Results: Eighteen patients (90%) in Group 1 felt pain (median, 6.5; range, 0–10). In Group 2, 11 patients (85%) felt pain after the first bolus (median, 6.0; range, 0–8) and 12 (92%) after the second one (median, 8; range, 0–10). We found no difference in pain grade between the groups after their first bolus (p = 0.33) or between the first bolus of Group 1 and the second bolus of Group 2 (p = 0.47). The median IOP reduction in Group 1 was 6.5 mmHg (range, 2–16) at 10 min and 7.0 mmHg (range, 4–16) at 20 min (p < 0.001 for both). In Group 2, the corresponding reductions after the second bolus were 9.0 mmHg (range, 4–10; p = 0.002) and 8.0 mmHg (range, 6–11; p = 0.002). The IOP reduction at 10 and 20 min was comparable between groups (p = 0.094 and p = 0.41, respectively). Conclusion: Splitting the bolus did not reduce pain associated with IVHTS. Single bolus is consequently recommended. [ABSTRACT FROM AUTHOR]

Purpose: To determine the risk of patients with an early diagnosis of heritable retinoblastoma being diagnosed with TRb (or pineoblastoma) asynchronously in a later stage and its effect on screening. Methods: We updated the search (PubMed and Embase) for published literature as performed by our research group in 2014 and 2019. Trilateral retinoblastoma (TRb) patients were eligible for inclusion if identifiable as unique and the age at which TRb was diagnosed was available. The search yielded 97 new studies. Three new studies and eight new patients were included. Combined with 189 patients from the previous meta‐analysis, the database included 197 patients. The main outcome was the percentage of asynchronous TRb in patients diagnosed before and after preset age thresholds of 6 and 12 months of age at retinoblastoma diagnosis. Results: Seventy‐nine per cent of patients with pineoblastoma are diagnosed with retinoblastoma before the age of 12 months. However, baseline MRI screening at time of retinoblastoma diagnosis fails to detect the later diagnosed pineal TRb in 89% of patients. We modelled that an additional MRI performed at the age of 29 months picks up 53% of pineoblastomas in an asymptomatic phase. The detection rate increased to 72%, 87% and 92%, respectively, with 2, 3 and 4 additional MRIs. Conclusions: An MRI of the brain in heritable retinoblastoma before the age of 12 months misses most pineoblastomas, while retinoblastomas are diagnosed most often before the age of 12 months. Optimally timed additional MRI scans of the brain can increase the asymptomatic detection rate of pineoblastoma. [ABSTRACT FROM AUTHOR]

Purpose: To assess the clinical relevance of myocilin (MYOC) gene variants as risk factors for glaucoma in literature and to estimate their prevalence in different populations. Methods: We reviewed the literature for published MYOC variants in glaucoma patients and estimated their prevalence in general population using gnomAD and BRAVO databases. We used several bioinformatics tools and the criteria of the American College of Medical Genetics and Genomics (ACMG) to assess the pathogenicity of the variants. We evaluated the carrier frequency of the variants in gnomAD, including its subpopulations. Results: We found 13 missense and 5 loss‐of‐function (LOF) reported variants in MYOC that were both probable pathogenic or risk variants and listed in gnomAD. Six likely pathogenic missense variants were p.(Cys25Arg), p.(Gln48His), p.(Gly326Ser), p.(Thr353Ile), p.(Thr377Met) and p.(Gly399Val). They were most prevalent in East and South Asia (frequency, 0.92% and 0.81%, respectively). The most common missense variants were p.(Thr353Ile) (0.91% in East Asia) and p.(Gln48His) (0.79% in South Asia). Five LOF variants were p.(Arg46Ter), p.(Arg91Ter), p.(Arg272Ter), p.(Gln368Ter) and p.(Tyr453MetfsTer11). We considered these glaucoma risk variants. They were most prevalent in the East Asian and the Finnish population (0.93% and 0.33%, respectively). Conclusion: Pathogenic MYOC variants appear to be population‐associated. Our results highlight allelic heterogeneity of MYOC variants in open‐angle glaucoma. Many of the probable pathogenic variants are over‐represented in some of the populations causing doubt of their status as monogenic disease‐causing variants. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the clinical features, diagnostic challenges, management, and prognosis of sebaceous carcinoma (SC) of the eyelids and periocular region in a Nordic country. Methods: Patients were identified from the Finnish Cancer Registry and the Helsinki University Hospital databases during the 21‐year period 1998–2018. Age, sex, location, clinical and histopathologic diagnosis, treatment and outcome were registered. Results: Sebaceous carcinoma (SC) was diagnosed in 32 patients. The incidence was 0.6 per million. Median age at the time of histopathologic diagnosis was 74 years, and 72% of patients were women. Diagnostic delay was often long, median 12 months. The most common cause for delay was misdiagnosis (72%): a chalazion in 34% and a benign tumour in 22%. The most common location was the upper eyelid (53%) and tumour type a solitary nodule (94%). The SC was not correctly diagnosed in 12 (40%) of 30 preoperative biopsies. The treatment for 31 (97%) patients was complete surgical removal with reconstruction. Conjunctival intraepithelial growth was found in 50%. The leading postoperative problem was ocular irritation (30%). During a median follow‐up of 58 months, two patients (6%) experienced a local recurrence and one patient died from metastatic SC. Conclusions: The estimated incidence of SC in Finland was somewhat higher than in other Western countries. The diagnosis was often markedly delayed. Especially differentiation from chalazion continues to be essential. To improve outcomes, it is essential to inform the pathologist about the possibility of SC in eyelid biopsies and specimens and ideally submit them to an ophthalmic pathology service. [ABSTRACT FROM AUTHOR]

Abstract: James Wardrop (1782–1869), a young Scottish surgeon and an early ophthalmologist in Edinburgh, is credited for describing in 1809 retinoblastoma as an entity in his treatise ‘Observations on Fungus Hæmatodes or Soft Cancer’. His treatise also reveals that Allan Burns (1781–1813), another young Scottish surgeon and anatomist, had invited Wardrop to assist in enucleating an eye from a 41‐year‐old Glasgow woman who, in retrospect, had a uveal melanoma. Her eye had become blind 4 months after symptoms of exudative retinal detachment had appeared, and it had become painful after a further 2–4 months. The tumour eventually perforated the sclera, and she died within a year thereafter of hepatic metastases. Burns and Wardrop went on to publish detailed parallel accounts of the symptoms, signs, ophthalmic pathology and post‐mortem findings regarding the primary, recurrent and metastatic tumour. Burns may have performed the post‐mortem after exhuming the body, a common occurrence in early 19th Century Scotland, a thriving hub for teaching morbid anatomy to young surgeons at the time. [ABSTRACT FROM AUTHOR]

Purpose To report the indications and the outcomes of keratoplasties in children over four decades. Methods A retrospective cohort study of patients aged 16 years or younger who underwent keratoplasty in the Helsinki University Eye Hospital during 1968-2011. Diagnosis, preoperative status, age at the time of surgery, surgical technique, complications and follow-up time were registered. Main outcome measures were visual acuity and graft survival as assessed by Kaplan-Meier analysis. The independent role of risk factors on outcomes was evaluated by Cox multivariate regression analysis. Results Forty-eight keratoplasties, 42 penetrating and six lamellar, were performed in 44 eyes of 39 children at the age of 4.5 months to 16 years (median, 12 years). Five patients had bilateral grafts, and five grafts were regrafts. The indication for keratoplasty was injury for 13 grafts, non-traumatic acquired corneal opacities for 11, keratoconus for eight, corneal dystrophy for seven, congenital corneal opacities for six and aniridia for three grafts. The cumulative proportion of clear grafts was 46% at 5 years postoperatively, and the median follow-up time of clear grafts was 5.1 years (range, 0.4-29 years) for 41 penetrating allografts ( PKP). Simultaneous intraocular surgery at the time of grafting [hazard ratio ( HR) 9.7], corneal vascularization ( HR 8.1) and regrafting ( HR 5.4) were the main independent risk factors for graft failure in this PKP cohort. The cumulative proportion of clear grafts was 84% at 5 years in the absence of any of these risk factors. PKP for keratoconus and corneal dystrophy yielded clear grafts in 83% of the eyes, and a visual acuity ≥0.3 (Snellen) in 75% of the eyes. Seventeen of the 20 graft failures were due to rejection. Conclusions Favourable graft survival was obtained in primary keratoplasties for non-vascularized corneal opacities performed without any other simultaneous intraocular surgery. Visual outcome was favourable in keratoconus and corneal dystrophies and poor in most eyes with injury. [ABSTRACT FROM AUTHOR]

Purpose: To report genetic findings in patients with suspected inherited retinal disorders (IRD) in a large Finnish cohort. Methods: The study was conducted retrospectively on IRD‐patients treated at the Department of Ophthalmology, Helsinki University Hospital between January 1, 2012, and December 31, 2020. Eligibility criteria were met by 786 patients. Clinical diagnosis, genetic testing method and result, relevant family history, and mode of inheritance were drawn from the electronic health registries. Results: Of the 638 patients who underwent genetic testing, 79% received a genetic diagnosis. The genetic findings corresponded to autosomal recessive (AR) inheritance in 242 patients, X‐linked in 158, and autosomal dominant (AD) in 94, whereas pathogenic variants in mitochondrial genes were found in 22 patients. The most common genetic diagnosis was a pathogenic variant in RS1 causing X‐linked retinoschisis (n = 86, 17% of all patients with a positive genetic finding). Of retinitis pigmentosa ‐associated genes, causative variants were most commonly found in CERKL (n = 43, 8.5%), RPGR (n = 31, 6.1%), and EYS (n = 25, 5.0%). CERKL variant c.375C > G, p.(Cys125Trp) and EYS variant c.1155 T > A, p.(Cys385Ter), both with known founder effects in the Finnish population, were frequently discovered (n = 69 and 53, respectively). Variants in the ABCA4 gene explained IRD in 24 patients. Pathogenic variants were also found in CHM (n = 26), OPA1 (n = 16), and CLRN1 (n = 16). Conclusions: The genetic causes of IRDs in Finland differ from other countries because of its isolated population history. Compared to similar studies in other countries, the percentage of patients with a positive genetic finding was higher (79%), which can partly be explained by the enriched founder mutations in the population. About 20% of the patients still lack a genetic diagnosis. These patients might have causative variants that are difficult to detect with current testing methods (such as complex structural variants) or the variants are in genes not yet associated with IRD. [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]