Rare single nucleotide variants in COL5A1 promoter do not play a major role in keratoconus susceptibility associated with rs1536482.

BACKGROUND: Keratoconus is a chronic degenerative disorder of the cornea characterized by thinning and cone-shaped protrusions. Although genetic factors play a key role in keratoconus development, the etiology is still under investigation. The occurrence of single-nucleotide polymorphisms (SNPs) associated with keratoconus in Russian patients is poorly studied. The purpose of this study was to validate whether three reported keratoconus-associated SNPs (rs1536482 near the COL5A1 gene, rs2721051 near the FOXO1 gene, rs1324183 near the MPDZ gene) are also actual for a Russian cohort of patients. Additionally, we investigated the COL5A1 promoter sequence for single-nucleotide variants (SNVs) in a subgroup of keratoconus patients with at least one rs1536482 minor allele (rs1536482+) to assess the role of these SNVs in keratoconus susceptibility associated with rs1536482. METHODS: This case-control study included 150 keratoconus patients and two control groups (main and additional, 205 and 474 participants, respectively). We performed PCR targeting regions flanking SNVs and the COL5A1 promoter, followed by Sanger sequencing of amplicons. The additional control group was genotyped using an SNP array. RESULTS: The minor allele frequency was significantly different between the keratoconus and control cohorts (main and combined) for rs1536482, rs2721051, and rs1324183 (p-value < 0.05). The rare variants rs1043208782 and rs569248712 were found in the COL5A1 promoter in two out of 94 rs1536482+ keratoconus patients. CONCLUSION: rs1536482, rs2721051, and rs1324183 were associated with keratoconus in a Russian cohort. SNVs in the COL5A1 promoter do not play a major role in keratoconus susceptibility associated with rs1536482.

Complete corneal ring (MyoRing) implantation versus MyoRing implantation combined with corneal collagen crosslinking for keratoconus: 3-year follow-up.

PURPOSE: To estimate the effectiveness of complete corneal ring (MyoRing) implantation compared with MyoRing implantation combined with corneal collagen crosslinking (CXL) for keratoconus treatment for 36 months follow-up. DESIGN: Retrospective cohort study. MATERIALS AND METHODS: MyoRing implantation was performed in a series of 78 patients (80 eyes) with keratoconus II-III Amsler classification, of these 39 eyes had MyoRing implantation combined with CXL. Implantation of a MyoRing in the corneal pocket was performed using a PocketMaker microkeratome and corneal intrastromal implantation system. During CXL, riboflavin solution 0.1% was injected into the corneal pocket through the incision tunnel and standard surface UVA irradiation (370 nm, 3 mW/cm2) was then applied from 5-cm distance for 30 min. RESULTS: Significant improvements in uncorrected distance visual acuity and corrected distance visual acuity were observed for both groups, which was relatively better 12 months after procedure in MyoRing alone group; however, in 36 months there was no difference between groups. Keratometry was reduced in both groups; after MyoRing implantation for 8.45 D and MyoRing + CXL for 9.43 D, the spherical equivalent decreased from 8.45 to 7.72 D and from 9.43 to 6.25 D, respectively. The cylinder decreased to 3.33 D with MyoRing alone and to 3.31 D with MyoRing + CXL. Corneal thickness remained nearly unchanged (from 433.69 ± 38.76 to 434.21 ± 34.98) in MyoRing group and decreased from baseline (from 426.93 ± 46.58 to 401.24 ± 39.12 µm) in MyoRing + CXL group 36 months postoperatively, which corresponds with pachymetry reduction after conventional CXL. CONCLUSION: Both MyoRing implantation and MyoRing combined with CXL were effective for treating keratoconus. At 36 months, there were slightly better outcomes in MyoRing + CXL group; however, in MyoRing alone group visual and refractive outcomes were stable overtime.

Prevalence and Associations of Keratoconus Among Children, Adults, and Elderly in the Population-Based Ural Eye Studies.

PURPOSE: To estimate prevalence and associations of keratoconus in populations in Russia with an age from childhood to seniority. METHODS: The study population consisted of the cohorts of 3 population-based studies performed in urban and rural areas within the same geographical region in Bashkortostan/Russia: the Ural Children Eye Study (UCES; age = 6-18 y; n = 4890), the Ural Eye and Medical Study (UEMS; age = >40 y; n = 5314), and the Ural Very Old Study (UVOS; age = >85 y; n = 651). Based on Scheimflug imaging, keratoconus was defined by a keratometric reading of ≥48 diopters (D) in any eye. RESULTS: The mean maximal and minimal corneal refractive power increased from the UCES (43.58 ± 1.50 D and 42.70 ± 1.42 D, respectively) to the UEMS (44.26 ± 1.70 D and 43.61 ± 1.76 D, respectively) and to the UVOS (45.1 ± 1.72 D and 43.98 ± 1.68 D, respectively). Correspondingly, keratoconus prevalence increased from the UCES (42/4890; 0.086%; 95% CI = 0.060, 0.112) to the UEMS (112/5314; 2.11%; 95% CI = 1.72, 2.49) and to the UVOS (42/651; 6.45%; 95% CI = 4.56, 8.34). In the UCES, higher keratoconus prevalence was associated (multivariable analysis) with higher birth order [odds ratio (OR) = 2.34; 95% CI = 1.32, 4.15; P = 0.004], lower birth weight (OR = 0.99; 95% CI = 0.99, 0.99; P < 0.001), and shorter axial length (OR = 0.15; 95% CI = 0.08, 0.30; P < 0.001). In the UEMS, keratoconus prevalence correlated with shorter axial length (OR = 0.15; 95% CI = 0.10, 0.23; P < 0.001), larger corneal volume (OR = 1.17; 95% CI = 1.09, 1.25; P = 0.001), thicker lens (OR = 2.27; 95% CI = 1.06, 5.28; P = 0.04), cortical cataract degree (OR = 1.02; 95% CI = 1.01, 1.04; P = 0.01), and higher stage of age-related macular degeneration (OR = 1.65; 95% CI = 1.09, 2.51; P = 0.02). In the UVOS, keratoconus prevalence correlated with lower educational level (OR = 0.84; 95% CI = 0.71, 0.99; P = 0.04) and lower dynamometric handgrip force (OR = 0.92; 95% CI = 0.88, 0.97; P = 0.003). CONCLUSIONS: In this study on multiethnic groups from Russia, keratoconus prevalence increased from the pediatric group (0.09%) to the adult group (2.11%) and seniority group (6.45%), correlated mostly with biometric ocular parameters and was in all age groups statistically independent of most systemic parameters.