Genetics in Keratoconus – What is New?

Moussa, Sarah; Grabner, Günther; Ruckhofer, Josef; Dietrich, Marie; Reitsamer, Herbert A.

doi:10.2174/1874364101711010201

Cited by 21 publications

(21 citation statements)

References 83 publications

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“…It usually appears in adolescence, progressing into the third or fourth decade [1]. Although of unknown etiology, it has been related to genetic factors [2] such as environmental factors [3,4].…”

Section: Introductionmentioning

confidence: 99%

A predictive model for early diagnosis of keratoconus

Castro-Luna

Pérez-Rueda

2020

BMC Ophthalmol

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Background: The diagnosis of keratoconus in the early stages of the disease is necessary to initiate an early treatment of keratoconus. Furthermore, to avoid possible refractive surgery that could produce ectasias. This study aims to describe the topographic, pachymetric and aberrometry characteristics in patients with keratoconus, subclinical keratoconus and normal corneas. Additionally to propose a diagnostic model of subclinical keratoconus based in binary logistic regression models. Methods: The design was a cross-sectional study. It included 205 eyes from 205 patients distributed in 82 normal corneas, 40 early-stage keratoconus and 83 established keratoconus. The rotary Scheimpflug camera (Pentacam® type) analyzed the topographic, pachymetric and aberrometry variables. It performed a descriptive and bivariate analysis of the recorded data. A diagnostic and predictive model of early-stage keratoconus was calculated with the statistically significant variables. Results: Statistically significant differences were observed when comparing normal corneas with early-stage keratoconus/ in variables of the vertical asymmetry to 90°and the central corneal thickness. The binary logistic regression model included the minimal corneal thickness, the anterior coma to 90°and posterior coma to 90°. The model properly diagnosed 92% of cases with a sensitivity of 97.59%, specificity 98.78%, accuracy 98.18% and precision 98.78%. Conclusions: The differential diagnosis between normal cases and subclinical keratoconus depends on the mínimum corneal thickness, the anterior coma to 90°and the posterior coma to 90°.

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Section: Introductionmentioning

confidence: 99%

A predictive model for early diagnosis of keratoconus

Castro-Luna

Pérez-Rueda

2020

BMC Ophthalmol

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“…Clinical signs of KC usually manifest first at puberty and in young adults leading to visual deterioration due to irregular astigmatism, myopia, and corneal scarring in about 20% of patients. [2,3] Although KC manifests in only one eye in most patients, the disease can progress to bilaterality in severely affected individuals. [4] Histologically, KC is characterized by impaired collagen secretion resulting from degeneration of keratocytes as well as by epithelial and stromal changes leading to disorganization of fibers involved in tissue resistance and stability.…”

Section: Introductionmentioning

confidence: 99%

Screening for Novel LOX and SOD1 Variants in Keratoconus Patients from Brazil

Gadelha¹,

Feitosa²,

Silva³

et al. 2020

JOVR

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Purpose: To investigate the presence of the variants of lysyl oxygenase (LOX) and superoxide dismutase 1 (SOD1) genes in Brazilian patients with advanced keratoconus. Methods: Donor genomic DNA extracted from blood samples was screened for 5’UTR, exonic LOX, and SOD1 variants in a subset of 26 patients presenting with advanced keratoconus (KISA > 1000% and I–S > 2.0) by Sanger sequencing. The impact of non-synonymous amino acid changes was evaluated by SIFT, PMUT, and PolyPhen algorithms. The Mutation Taster tool was used to evaluate the potential impact of formation of new donor and acceptor splice sites in the promoter region of affected volunteers carrying sequence variants. A 7-base SOD1 deletion (IVS2 + 50del7bp) previously associated with keratoconus was screened in 140 patients presenting classical keratoconus by gel fragment analysis, and positive samples were sequenced for confirmation. Results: We found an unreported missense variant in LOX exon 6 in one heterozygous patient, leading to substitution of proline with threonine at residue 392 (p. Thr392Pro) of LOX protein sequence. This mutation was predicted to be potentially damaging to LOX protein. Another LOX variant, Arg158Gln, was also detected in another patient but predicted to be non-pathogenic. Two additional new polymorphisms in LOX 5’UTR region (–116C > T and –58C > T) were found in two patients presenting with advanced keratoconus and were predicted to modulate or create donor/acceptor splice sites in LOX transcripts. Additionally, SOD1 deletion was detected in one patient presenting with severe keratoconus, not in control samples. Conclusion: We described three novel LOX polymorphisms identified for the first time in Brazilian patients with advanced keratoconus, as well as a previously described SOD1 deletion strongly associated with keratoconus. A possible role of these variants in modulating transcript levels in the cornea of affected individual requires further investigation.

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“…The beginning in youth could influence people’s learning and their quality of life. Although unknown etiology, it has been related to genetic 5 and environmental factors 7 – 9 . Keratoconus incidence and prevalence are very variable.…”

Section: Introductionmentioning

confidence: 99%

A model of visual limitation in patients with keratoconus

Pérez-Rueda

Castro-Luna

2020

Sci Rep

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This paper aims to calculate a relevance model of visual limitation (V.L.) in keratoconus patients based on refractive and topographic parameters. A cross-sectional study was carried out in Torrecárdenas Hospital, Almería, Spain, between February 2018 and July 2019. It included 250 keratoconus patients. Two groups were created according to a grading system of V.L. based on RETICS (Red Temática de Investigación Cooperativa en Salud) classification: keratoconus patients with no V.L. (best spectacle-corrected visual acuity (BSCVA) ≤ 0.05 logMAR) and keratoconus patients with V.L. (BSCVA > 0.05 logMAR). Correlations and a binary logistic regression were established. V.L. was correlated with maximum curvature (r = 0.649, p < 0.001) and root mean square higher-order aberrations (HOARMS) (r = 0.625, p < 0.001). Binary logistic regression included V.L. as the dependent variable and spherical equivalent, HOARMS, spherical aberration and interaction between the anterior and posterior vertical coma as independent variables. The model was a good fit. Area under the curve (A.U.C.) of receiver operating characteristic (R.O.C.) curve was 0.924, sensitivity 91.90%, specificity 83.60%, accuracy 88.94%; and precision 91.17%. Binary logistic regression model of V.L. is a good fit model to predict the early loss of visual acuity in keratoconus patients.

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Genetics in Keratoconus – What is New?

Cited by 21 publications

References 83 publications

A predictive model for early diagnosis of keratoconus

A predictive model for early diagnosis of keratoconus

Screening for Novel LOX and SOD1 Variants in Keratoconus Patients from Brazil

A model of visual limitation in patients with keratoconus

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