Non-syndromic inherited retinal diseases in Poland: Genes, mutations, and phenotypes.

Purpose: Inherited retinal diseases (IRDs), encompassing many clinical entities affecting the retina, are classified as rare disorders. Their extreme heterogeneity made molecular screening in the era before next-generation sequencing (NGS) expensive and time-consuming. Since then, many NGS studies of IRD molecular background have been conducted in Western populations; however, knowledge of the IRD mutational spectrum in Poland is still limited. Until now, there has been almost no comprehensive analysis of this particular population regarding the molecular basis and inheritance of IRDs. Therefore, the purpose of this study was to gain knowledge about the type and prevalence of causative variants in the Polish population. Methods: We recruited 190 Polish families with non-syndromic IRDs, including Stargardt disease (STGD), retinitis pigmentosa (RP), cone- and cone-rod dystrophy (CD/CRD), achromatopsia, and congenital stationary night blindness. A pool of molecular inversion probes was used, which targeted 108 genes associated with non-syndromic IRDs known in 2013. We applied filtering for known variants occurring with an allele frequency >0.5% in public and in-house databases, with the exception of variants in ABCA4, when the frequency filter was set to 3.0%. Hypomorphic p.(Asn1868Ile) was added manually. In the case of novel missense or splicing variants, we used in silico prediction software to assess mutation causality. Results: We detected causative mutations in 115 of the 190 families with non-syndromic IRD (60.2%). Fifty-nine individuals with STGD, RP, and CD/CRD carried causal variants in ABCA4. Novel single nucleotide variants were found in ABCA4, CEP290, EYS, MAK, and CNGA3. The complex allele c.[1622T>C;3113C>T], p.[Leu541Pro;Ala1038Val] was found in 33 individuals with ABCA4-associated disorders, which makes it the most prevalent allele in the Polish population (17% of all solved cases). Diagnosis was reevaluated in 16 cases. Conclusions: Previously, there were no comprehensive reports of IRDs in the Polish population. This study is the first to indicate that the most common IRDs in Poland are ABCA4-associated diseases, regardless of the phenotype. In Polish patients with RP, the second most prevalent causal gene was RHO and the third RPGR, while there were not as many mutations in EYS as in Western populations. The number of initial erroneous diagnoses may be the result of limited access to diagnostics with advanced tools, such as electroretinography; however, it is necessary to raise awareness among Polish ophthalmologists of rare IRDs. Additionally, it must be emphasized that in some cases genetic analysis of the patient is necessary to achieve an accurate diagnosis.

Genetic Spectrum of ABCA4-Associated Retinal Degeneration in Poland.

Mutations in retina-specific ATP-binding cassette transporter 4 (ABCA4) are responsible for over 95% of cases of Stargardt disease (STGD), as well as a minor proportion of retinitis pigmentosa (RP) and cone-rod dystrophy cases (CRD). Since the knowledge of the genetic causes of inherited retinal diseases (IRDs) in Poland is still scarce, the purpose of this study was to identify pathogenic ABCA4 variants in a subgroup of Polish IRD patients. We recruited 67 families with IRDs as a part of a larger study. The patients were screened with next generation sequencing using a molecular inversion probes (MIPs)-based technique targeting 108 genes involved in the pathogenesis of IRDs. All identified mutations were validated and their familial segregation was tested using Sanger sequencing. In the case of the most frequent complex allele, consisting of two variants in exon 12 and 21, familial segregation was tested using restriction fragment length polymorphism (RFLP). The most prevalent variant, a complex change c.[1622T>C;3113C>T], p.[Leu541Pro;Ala1038Val], was found in this cohort in 54% of all solved ABCA4-associated disorder cases, which is the highest frequency reported thus far. Additionally, we identified nine families displaying a pseudo-dominant mode of inheritance, indicating a high frequency of pathogenic variants within this population.

Comparison of Visual Field Measurement with Heidelberg Edge Perimeter and Humphrey Visual Field Analyzer in Patients with Ocular Hypertension.

BACKGROUND: Glaucoma is a group of eye diseases which result in damage to the optic nerve and vision loss. The most important examination in glaucoma patients is visual field assessment. One of the newer perimeters is Heidelberg Edge Perimeter (HEP). OBJECTIVES: The aim of the study was to compare visual field measurements made with Humphrey II 740 Visual Field (Carl Zeiss Meditec) and Heidelberg Edge Perimeter (HEP) (Heidelberg Engineering). FDF stimulus (flicker defined form) in HEP stimulates magnocellular retinal cells, which are the first to be damaged in the early stage of glaucoma. Even a small loss of magnocellular cells may influence HEP visual field. MATERIAL AND METHODS: The observed group consisted of 45 patients (82 eyes), age 60 ± 9.8 years, glaucoma suspects, not treated pharmacologically or surgically before, with intraocular pressure ≥ 22 mm Hg. Visual field values were measured with two different devices: Humphrey II 740 Visual Field (Carl Zeiss Meditec, Jena, Germany) and Heidelberg Edge Perimeter (Heidelberg Engineering, Heidelberg, Germany). The patients were divided into two groups: Group 1 - tested with SITA Standard program on Humphrey perimeter and ASTA Standard HEP, and Group 2 - tested with SITA Fast program on Humphrey perimeter and ASTA Standard on HEP. RESULTS: Few positive ΔMD results (ΔMD = MD HEP - MD HUM) were obtained in Groups 1 and 2, which means that the deviation value on the HEP perimeter was only slightly higher than the mean deviation value on Humphrey. Therefore, one can conclude that HEP perimeter may detect visual field defects with greater precision. The visual field measurements between ASTA Standard on HEP and SITA Standard on Humphrey as well as ASTA Standard on HEP and SITA Fast on Humphrey are not equal: MD values on HEP perimeter are lower than MD on Humphrey, which can mean that HEP perimeter provides more precise results and shows even early visual field lesions. CONCLUSIONS: HEP perimeter measures visual field defects with greater precision so it should be taken into consideration for earlier glaucoma detection in routine ophthalmological diagnosis.