[Update on Current Care Guideline: Glaucoma]. / Avokulmaglaukooma.

The up-date of the Finnish Current Care Guideline for glaucoma is based primarily on systematic reviews searched up by March 2014. The recommendations are presented in nine tables, which are based on 95 graded statements with evidence summaries. The online availability (www.kaypahoito.fi) of the English translation of guideline and evidence summaries enables the verification of the evidence and recommendations. Ten external stakeholders gave a mean value of 1.8 (range of 1 = completely agree to 4 = completely disagree) for the structured questions (e.g. definitions, goals, questions, target users) and judged the evidence and the recommendations.

[Current status of genome research on open-angle glaucoma in Finland]. / Avokulmaglaukooman geenitutkimuksen nykytilanne Suomessa.

Loss of vision and visual impairment due to glaucoma can be prevented or delayed, if the disease is detected at an early stage. The most important risk factors for open-angle glaucoma include age, elevated intraocular pressure, exfoliation of the lens, i.e. exfoliation syndrome, and genetic factors. To date, genetic studies on glaucoma have revealed more than 20 gene loci and three candidate genes, myocilin (MYOC), optineurin (OPTN) and WD repeat domain 36 (WDR36). A mutation in both the MYOC and WDR36 genes has been found in Finnish families.

Association of LOXL1 gene with Finnish exfoliation syndrome patients.

In this study, three single-nucleotide polymorphisms (SNPs) on the lysyl oxidase-like 1 (LOXL1) gene associated with exfoliation syndrome (XFS) and exfoliation glaucoma (XFG) were investigated in the Finnish population. A case-control study of 59 sporadic patients with XFS, 82 with XFG, 71 with primary open-angle glaucoma (POAG) and 26 individuals without these disorders from the southern Finnish population, and a family study of an extended family with 28 patients with XFS or XFG and 92 unaffected relatives from Kökar islands, Southwestern Finnish archipelago, were conducted. Anonymous blood donors (n=404) were studied as population-based controls. Three SNPs, rs1048661 (R141L), rs3825942 (G153D) and rs2165241, of the LOXL1 gene were genotyped by PCR sequencing. Association and linkage analyses were carried out. In both case-control and family materials, significant association for allele G of rs1048661 (P=2.65 x 10(-5); P=0.0007), allele G of rs3825942 (P=2.24 x 10(-8); P=0.49) and allele T of rs2165241 (P=2.62 x 10(-13); P<0.0001) was found in XFS/XFG. However, linkage was not observed for LOXL1 risk alleles. The corresponding three-locus haplotype GGT increased the risk of XFS/ XFG nearly 15-fold relative to low-risk haplotype GAC (odds ratio (OR): 14.9, P=1.6 x 10(-16)). In conclusion, the earlier reported polymorphisms of the LOXL1 gene showed significant association also in the Finnish population.

Genome-wide scan of exfoliation syndrome.

PURPOSE: Exfoliation syndrome (XFS) is an age-related ocular condition that is characterized by the accumulation of fibrillogranular extracellular material in intra- and extraocular tissues. The purpose of the present study was to identify the genetic basis of XFS in a large Finnish family. METHODS: A genome-wide scan with 1000 microsatellite markers was performed in an extended family from an island in the southwestern Finnish archipelago where XFS demonstrates an autosomal dominant mode of inheritance with incomplete penetrance. Two-point linkage analyses were performed with MLINK and multipoint linkage, using the Vitesse program. RESULTS: Five chromosomal regions with markers showing two-point LOD scores more than 1.5 was identified by using a dominant mode of inheritance for the XFS trait. The most promising locus was assigned to 18q12.1-21.33 with a maximum two-point LOD score of 3.45 and a multipoint LOD score of 4.2. Some evidence of linkage was obtained at chromosomes 2q, 17p, and 19q, which were suggested in earlier reports to be possible regions of linkage to primary open-angle glaucoma (POAG). CONCLUSIONS: The study presented herein offers a starting point to unravel the molecular background of XFS.

Exfoliation syndrome: prevalence and inheritance in a subisolate of the Finnish population.

PURPOSE: To estimate the prevalence of pseudoexfoliation syndrome or exfoliation syndrome (ES) in a cross-sectional study and during a long-term follow-up, and to analyse how ES has been inherited in a large pedigree on an isolated population of Kökar island in southern Finland. METHODS: In a population-based study conducted between 1960 and 1962, a comprehensive ophthalmological examination was performed on 595 subjects (85% of the population). From then until 2002, 965 subjects were examined at least once. A pedigree was constructed for all ES-affected subjects according to genealogical studies. The genetic contribution to ES was investigated in this pedigree by segregation analysis and the heritability of the intraocular pressure (IOP) quantitative trait estimated using SOLAR and SAGE software. RESULTS: In the cross-sectional study, the prevalence of ES was 8.1% for 247 subjects over 50 years of age (males 7%, females 9%) and increased to 18.4% for 70 subjects over 70 years of age (males 13%, females 25%). In addition, two females less than 50 years of age were ES-affected. Between 1960 and 2002, 76 (14.3%) of 530 subjects over 50 years of age had ES [23 males (10%) and 53 females (18%)]. Exfoliation glaucoma (EG) was found more often in males (11 patients, 48%) than in females (13 patients, 25%) whereas primary open-angle glaucoma (POAG) was almost as frequent in males (seven patients, 3%) as in females (five patients, 2%). The relative risk (RR) of glaucoma (ES versus no ES) was 11.9 [95% confidence interval (CI) 6.2-22.9] for all the subjects - 14.6 for males (95% CI 6.3-34.0) and 11.8 for females (95% CI 4.4-31.6). Seventy-five pedigrees of 78 ES-affected patients were linked together into one large pedigree with 110 nuclear families. The segregation ratio of ES was 18% (8% for males, 24% for females) when both parents were unaffected, and 16% (9% for males, 27% for females) when at least one parent was affected. The heritability of IOP was estimated to be 30%. CONCLUSION: In this population-based family study, ES is consistent with an autosomal dominant trait with incomplete penetrance, where the penetrance is more reduced in males than in females. However, the presence of ES was a greater risk factor for developing glaucoma in males than in females.

Lifetime visual disability in open-angle glaucoma and ocular hypertension.

PURPOSE: To study how many of the patients with treated glaucoma or ocular hypertension go blind during their lifetime and which factors are associated with blindness. PATIENTS: The data on 106 consecutive patients who had died between 1991 and 2002 was retrospectively evaluated. At diagnosis 39 patients had primary open-angle glaucoma, 27 had exfoliation glaucoma, and 40 had ocular hypertension. METHODS: Clinical records and causes of death were reviewed. Visual disability at the last visit before death was evaluated. Outcome measures were visual handicap and blindness based on visual acuity and/or visual fields. RESULTS: At the last visit, 17 patients [16%, 95% confidence interval (CI) 9-23] were visually handicapped. Thirteen patients (14%) were bilaterally blind. Glaucoma was the cause of blindness in one or both eyes in 16 patients (15%, 95% CI 8-22) and in both eyes in 6 patients (6%, 95% CI 1-10). In the analysis of only 1 eye of each patient, the cumulative incidence of glaucoma-caused blindness was 6% (95% CI 2-11) at 5 years, 9% (95% CI 4-15) at 10 years, and 15% (95% CI 9-23) at 15 years. An advanced stage of glaucoma at diagnosis, fluctuation in intraocular pressure during treatment, the presence of exfoliation syndrome, and poor patient compliance increased the occurrence of blindness. Positive family history of glaucoma and vascular causes of death had no effect on visual outcome. CONCLUSIONS: Glaucoma-caused blindness was associated with an advanced stage of glaucoma at diagnosis, fluctuation of intraocular pressure during treatment, the presence of exfoliation syndrome, and poor patient compliance. The risk of going blind from glaucoma in both eyes was 6%.

Exclusion of 14 candidate loci for primary open angle glaucoma in Finnish families.

PURPOSE: The aim of the present study was to examine the genetic background of primary open angle glaucoma (POAG) in the Finnish population by analyzing previously reported candidate loci GLC1B on 2cen-q13, GLCIC on 3q21-q24, GLC1D on 8q23, GLC1F on 7q35-q36, as well as other candidate regions on chromosomes 2p14, 2q33-34, 10p12-13, 14q11, 14q21-22, 17p13, 17q25, and 19q12-14. In addition, we analysed loci for the MYOC gene on 1q23-24 and the OPTN gene on 10p14-15. METHODS: Eight Finnish families (92 family members; 27 individuals with POAG; 19 individuals with ocular hypertension or glaucoma suspicion) were genotyped using 35 microsatellite markers on the candidate loci and analyzed for linkage. RESULTS: No significant evidence for linkage was found in two point and multipoint linkage analyses to the tested markers in the analyzed families. CONCLUSIONS: Our results support further genetic heterogeneity underlying POAG and encourage a search of novel genetic loci and predisposing genes in order to understand the genetic mechanisms underlying POAG.

The role of TIGR and OPTN in Finnish glaucoma families: a clinical and molecular genetic study.

PURPOSE: The aim of the present study was to analyze the role of the two primary open angle glaucoma (POAG) genes, trabecular meshwork-induced glucocorticoid response (TIGR/MYOC) and optineurin (OPTN), in Finnish glaucoma families originating from southern coast of Finland. METHODS: In total, 136 patients were examined to determine their ophthalmological status. Genealogical studies were performed using church records. Direct PCR-sequencing of the coding regions of the TIGR and OPTN genes was performed in 11 subjects. RESULTS: Inheritance resembling autosomal dominant mode was detected in eight families with open-angle glaucoma. Glaucoma was diagnosed in 53 subjects, of them 44 had POAG, 7 had exfoliative glaucoma (EG), and 2 had other types of glaucoma. Of the first degree relatives, 22 out of 79 (28%) were glaucoma suspects. No mutations in these families were identified. Instead, two polymorphisms in the TIGR gene and three polymorphisms in the OPTN gene, in which one was novel, were found in three phenotypes: POAG, exfoliative glaucoma, and exfoliation syndrome. CONCLUSIONS: Our results give evidence that novel, unidentified genes will underlie POAG and exfoliation syndrome in the Finnish population.

Exfoliation syndrome: frequency, gender distribution and association with climatically induced alterations of the cornea and conjunctiva.

PURPOSE: To investigate exfoliation syndrome (ES) in order to elucidate gender distribution and the roles of genetic and climatic factors in its manifestation. MATERIAL AND METHODS: We studied the gender distribution of ES and the association between ES and the appearance of certain climatically induced disorders (pterygium, climatic droplet keratopathy) and the size of pingueculae in populations living in the Arctic region, in temperate regions and in tropical regions. This involved a total of 11 samples taken in eight different countries, comprising 2206 persons of both genders over the age of 50 years. RESULTS: A total of 1051 males were investigated for ES and 147 of them (14.0%) were found to have it. The corresponding figures for females were 1093 and 177 (16.2%). After standardization according to age, no systematic difference between the genders was found in the study. The frequency of ES varied greatly. It was not observed at all in the Inuit (Eskimos) but was found most frequently (about 30%) among the Saami (Lapps), Aland Islanders, Finns, Icelanders and Russians over 70 years of age. After the age of 50, the frequency of ES increases rapidly with age in all populations. However, the curves for ES in people living in the tropics show a delay of about 10 years. In contrast, the frequency of climatically caused changes (pterygium, climatic keratopathy and pronounced pinguecula) mostly peaks at the age of 50 years and is highest in the tropics and in the Arctic. Males in these regions tended to be more affected by climatically caused changes than females. Likewise, in tropical climates, where radiation from the sun is strong, and in Lapland and Novosibirsk, where there is radiation from snow, males showed more evidence of ES than females. However, examination of 506 patients from a private practice in South Finland, who were under observation for glaucoma or for risk of glaucoma, showed females to be in the majority of those with ES. CONCLUSIONS: As a rule, climate does not appear to influence the occurrence of ES. However, in tropical countries, where radiation from the sun is strong, ES was more common among males than among females. In the light of its peculiar population distribution, even when climatic factors are considered, there would appear to be an important genetic factor involved in the manifestation of ES.