A Mendelian randomization study on the causal relationship between smoking, alcohol consumption, and the development of myopia and astigmatism.

The influence of environmental factors like smoking and alcohol on myopia and astigmatism is controversial. However, due to ethical concerns, alternative study designs are urgently needed to assess causal inference, as mandatory exposure to cigarettes and alcohol is unethical. Following comprehensive screenings, 326 single nucleotide polymorphisms (SNPs) related to myopia and astigmatism were included in the dataset. To validate the causal association between exposures such as cigarette smoking, alcohol consumption, and coffee intake, and outcomes namely astigmatism and myopia, five regression models were employed. These models encompassed MR-Egger regression, random-effects inverse-variance weighted (IVW), weighted median estimator (WME), weighted model, and simple model. The instrumental variables utilized in these analyses were the aforementioned SNPs. Apply Cochran's Q test to determine heterogeneity of SNPs; if heterogeneity exists, focus on IVW model results. The IVW model showed a 1.379-fold increase in the risk of astigmatism (OR = 1.379, 95%CI 0.822~2.313, P = 0.224) and a 0.963-fold increase in the risk of myopia (OR = 0.963, 95%CI 0.666~1.393, P = 0.841) for each unit increase in smoking. For each unit increase in coffee intake, the risk of astigmatism increased 1.610-fold (OR = 1.610, 95%CI 0.444~5.835, P = 0.469) and the risk of myopia increased 0.788-fold (OR = 0.788, 95%CI 0.340~1.824, P = 0.578). For each additional unit of alcohol consumption, the risk of astigmatism increased by 0.763-fold (OR = 0.763, 95%CI 0.380~1.530, P = 0.446), and none of the differences were statistically significant. However, for each unit of alcohol consumption, the risk of myopia increased by 1.597 times, and the difference was statistically significant (OR = 1.597, 95%CI 1.023~2.493, P = 0.039). The findings indicate that alcohol consumption is a risk factor for myopia but smoking and coffee intake do not affect its development. Additionally, there is no association between smoking, alcohol consumption, coffee intake, and the risk of astigmatism.

Association of PDGFRA polymorphisms with the risk of corneal astigmatism in a Japanese population.

Corneal astigmatism is reportedly associated with polymorphisms of the platelet-derived growth factor receptor alpha (PDGFRA) gene region in Asian populations of Chinese, Malay, and Indian ancestry and populations of European ancestry. In this study, we investigated whether these PDGFRA polymorphisms are associated with corneal astigmatism in a Japanese population. We recruited 1,535 cases with corneal astigmatism (mean corneal cylinder power across both eyes: ≤ - 0.75 diopters [D]) and 842 controls (> - 0.75 D) to genotype 13 single-nucleotide polymorphisms (SNPs) in the PDGFRA gene region. We also performed imputation analysis in the region, with 179 imputed SNPs included in the statistical analyses. The PDGFRA SNPs were not significantly associated with the cases with corneal astigmatism ≤ - 0.75 D. However, the odds ratios (ORs) of the minor alleles of SNPs in the upstream region of PDGFRA, including rs7673984, rs4864857, and rs11133315, tended to increase according to the degree of corneal astigmatism, and these SNPs were significantly associated with the cases with corneal astigmatism ≤ - 1.25 D or ≤ - 1.50 D (Pc < 0.05, OR = 1.34-1.39). These results suggest that PDGFRA SNPs play a potential role in the development of greater corneal astigmatism.

Genetic causes of nystagmus, foveal hypoplasia and subnormal visual acuity- other than albinism.

Background: To describe genetic molecular findings in individuals with congenital nystagmus, foveal hypoplasia, and subnormal vision, with normal ocular pigmentation (absence of diffuse transillumination or transparent retinal pigment typical for albinism).Methods: This is a retrospective, multicenter study of ophthalmic, systemic, and genetic features, as collected from medical records of patients diagnosed with infantile nystagmus and foveal hypoplasia. Ophthalmic findings include best-corrected visual acuity (BCVA), biomicroscopic examination, cycloplegic refraction, retinal examination, macular optical coherence tomography, and electroretinography. Genetic information was retrieved from the participating genetic clinics and included ethnicity and molecular diagnosis.Results: Thirty-one individuals met the inclusion criteria and had a secure molecular diagnosis. Mutations in two genes predominated, constituting 77.4% of all the represented genes: SLC38A8 (45.1%) and PAX6 (32.3%). Seventy-eight percent of the subjects who had a measurable BCVA had moderate and severe visual impairment (range 20/80 to 20/270). Most patients with a mutation in SLC38A8 had mild to moderate astigmatism, while most patients with PAX6 mutation had moderate and severe myopia. Patients in the PAX6 group had variable degrees of anterior segment manifestations.Conclusion: In our cohort, the main causative genes for congenital nystagmus and foveal hypoplasia in normally pigmented eyes were SLC38A8 and PAX6. A mild phenotype in PAX6 mutations may be an under-diagnosed cause of nystagmus and foveal hypoplasia. Reaching an accurate genetic diagnosis is essential for both the patients and their family members. This enables predicting disease prognosis, tailoring correct follow-up, and providing genetic counseling and family planning to affected families.

Alteraciones de la motilidad ocular en el síndrome de Kabuki / Changes in ocular motility in Kabuki síndrome

El síndrome de Kabuki es una enfermedad genética rara debida a una mutación genética en los genes KMT2D y KDM6A, que afecta a múltiples órganos, entre ellos los ojos, en la mayoría de los pacientes. Las características clínicas más típicas son: facies peculiar, baja estatura, anormalidades esqueléticas y bajo coeficiente intelectual. Las manifestaciones oculares más frecuentes son el estrabismo, la ptosis y los defectos refractivos. Presentamos una serie de casos de 5 pacientes (3 mujeres), 4 de ellos con estrabismo en forma de esotropía, hiperacción de oblicuos inferiores e hipofunción de oblicuos superiores asociado a un síndrome V. Son pocos los casos publicados de síndrome de Kabuki que describan las afectaciones oftalmológicas y las estrabológicas. Podría ser conveniente la realización de resonancias magnéticas orbitarias para detectar cambios en los trayectos musculares que estén relacionados con la patología de los movimientos oculares encontrados

Kabuki syndrome is a rare genetic disorder, caused by mutation in the KMT2D or KDM6A genes, which affects several organs in the majority of patients, among which are the eyes. The most typical clinical characteristics are mental retardation, postnatal growth retardation, skeletal anomalies, and characteristic facial features. As the eyes are affected in most of the cases, ophthalmological examination is recommended for the early detection of ocular anomalies, in order to prevent visual impairment. The most frequent ocular signs are strabismus, ptosis, and refractive anomalies. A series of cases of Kabuki syndrome is described in five children, four of whom exhibited strabismus with esotropia, over action of inferior oblique muscles, and under action of superior oblique muscles associated with a V pattern. Most published papers do not report or might underestimate the ocular problems. It may be appropriate to perform orbital magnetic resonances in order to detect changes in the muscle paths that are related to the pathology of the eye movements found

Changes in ocular motility in Kabuki syndrome. / Alteraciones de la motilidad ocular en el síndrome de Kabuki.

Kabuki syndrome is a rare genetic disorder, caused by mutation in the KMT2D or KDM6A genes, which affects several organs in the majority of patients, among which are the eyes. The most typical clinical characteristics are mental retardation, postnatal growth retardation, skeletal anomalies, and characteristic facial features. As the eyes are affected in most of the cases, ophthalmological examination is recommended for the early detection of ocular anomalies, in order to prevent visual impairment. The most frequent ocular signs are strabismus, ptosis, and refractive anomalies. A series of cases of Kabuki syndrome is described in five children, four of whom exhibited strabismus with esotropia, over action of inferior oblique muscles, and under action of superior oblique muscles associated with a V pattern. Most published papers do not report or might underestimate the ocular problems. It may be appropriate to perform orbital magnetic resonances in order to detect changes in the muscle paths that are related to the pathology of the eye movements found.

Origins of Refractive Errors: Environmental and Genetic Factors.

Refractive errors are the product of a mismatch between the axial length of the eye and its optical power, creating blurred vision. Uncorrected refractive errors are the second leading cause of worldwide blindness. One refractive error currently attracting significant scientific interest is myopia, mostly owing to the recent rise in its prevalence worldwide and associated ocular disease burden. This increase in myopia prevalence has also been rapid, suggesting environmental influences in addition to any genetic influences on eye growth. This review defines refractive errors, describes their prevalence, and presents evidence for the influence of genetic and environmental factors related to refractive error development.

Heritability of Corneal Curvature and Pentacam Topometric Indices: A Population-Based Study.

PURPOSE: To investigate familial aggregation of anterior and posterior corneal curvature, corneal astigmatism, and some corneal topometric indices using the Pentacam. METHODS: Of 3,851 eligible individuals who resided in the selected areas, 2,779 met the conditions for analysis. However, analysis was limited to families whose Pentacam measures were available for at least 2 family members (father or mother and a child), resulting in 1,383 individuals in 382 families. All selected subjects underwent a set of examinations, including refraction, uncorrected and corrected visual acuity measurement, slitlamp biomicroscopy, and Pentacam imaging. Heritability estimation was used to calculate familial aggregation. RESULTS: The results of our study showed a fairly high corneal curvature heritability. The heritability of K2 and K1 in the anterior surface was 58.61% (95% confidence interval [CI], 54.99-62.23) and 55.82% (95% CI, 52.66-58.98), respectively. The heritability of posterior corneal curvature was slightly higher than that of the anterior corneal curvature. The heritability of K2 and K1 in the posterior surface was 63.42% (95% CI, 60.07-66.77) and 59.67% (95% CI, 55.85-63.49), respectively. Investigation of the quantitative topographic corneal indices showed that index of surface variance (ISV), central keratoconus index, and index of vertical asymmetry (IVA) had the highest levels of heritability (81.2% [95% CI, 73.64-88.76], 75.21% [95% CI, 67.19-82.28], and 66.46% [95% CI, 61.99-70.93], respectively). However, keratometric power deviation and index of height asymmetry had the lowest heritability levels (7.48% 95% CI, [4.94-10.02] and 18.31% [95% CI, 16.07-20.55], respectively). CONCLUSION: The familial aggregation and relatively high heritability of the corneal curvature and some keratoconus-related indices, such as ISV and IVA, confirm a high correlation between these phenotypes and genetic factors and warrant further investigation of the genetic mechanisms in keratoconus.

Síndrome de Moebius incompleto. Presentación de un caso clínico / Incomplete Moebius syndrome. Clinical case presentation

RESUMEN El síndrome de Moebius es un trastorno polimalformativo no progresivo que se caracteriza por parálisis facial congénita. Se define como una "parálisis congénita de los núcleos de los pares craneales VI y VII, cuyo espectro clínico es variable y se asocia a múltiples malformaciones óseas y musculares. Es poco frecuente y de etiología vascular, genética o multifactorial. El trabajo, basándose en los fundamentos teóricos más actualizados, pretendió describir las manifestaciones clínicas del síndrome de Moebius y su posible etiología, a propósito de un caso. Se trató de un paciente de 11 años de edad, que al nacimiento presentó asimetría facial, desviación de la comisura labial hacia la izquierda, boca semiabierta, lagrimeo constante y pabellón auricular derecho malformado. Por ser una entidad clínica poco conocida, se expuso el presente caso, portador de un síndrome de Moebius incompleto de causa vascular y multifactorial (AU).

ABSTRACT Moebius syndrome is a non-progressive poli-formative disorder characterized by facial congenital paralysis. It is defined as a congenital paralysis of the VI and VII cranial nerves nuclei, the clinical spectrum of which is variable and associated to several bone and muscular malformations. It is few frequent and has vascular, genetic or multifactorial etiology. This work, based on more updated theoretical fundaments, pretended to describe the clinical manifestations of the Moebius syndrome and its possible etiology on the purpose of a case. It is the case of a patient, aged 11 years, who presented facial asymmetry, lips commissure deviation to the left, semi-opened mouth, constant lagrimeo and deformed right auricular pavilion (pabellon auricular). Because it is a little known clinical entity, this case of a patient having an incomplete Moebius syndrome of vascular and multifactorial cause was presented (AU).

Síndrome de Moebius incompleto. Presentación de un caso clínico / Incomplete Moebius syndrome. Clinical case presentation

RESUMEN El síndrome de Moebius es un trastorno polimalformativo no progresivo que se caracteriza por parálisis facial congénita. Se define como una "parálisis congénita de los núcleos de los pares craneales VI y VII, cuyo espectro clínico es variable y se asocia a múltiples malformaciones óseas y musculares. Es poco frecuente y de etiología vascular, genética o multifactorial. El trabajo, basándose en los fundamentos teóricos más actualizados, pretendió describir las manifestaciones clínicas del síndrome de Moebius y su posible etiología, a propósito de un caso. Se trató de un paciente de 11 años de edad, que al nacimiento presentó asimetría facial, desviación de la comisura labial hacia la izquierda, boca semiabierta, lagrimeo constante y pabellón auricular derecho malformado. Por ser una entidad clínica poco conocida, se expuso el presente caso, portador de un síndrome de Moebius incompleto de causa vascular y multifactorial (AU).

ABSTRACT Moebius syndrome is a non-progressive poli-formative disorder characterized by facial congenital paralysis. It is defined as a congenital paralysis of the VI and VII cranial nerves nuclei, the clinical spectrum of which is variable and associated to several bone and muscular malformations. It is few frequent and has vascular, genetic or multifactorial etiology. This work, based on more updated theoretical fundaments, pretended to describe the clinical manifestations of the Moebius syndrome and its possible etiology on the purpose of a case. It is the case of a patient, aged 11 years, who presented facial asymmetry, lips commissure deviation to the left, semi-opened mouth, constant lagrimeo and deformed right auricular pavilion (pabellon auricular). Because it is a little known clinical entity, this case of a patient having an incomplete Moebius syndrome of vascular and multifactorial cause was presented (AU).

Clinical and imaging characteristics of posterior column ataxia with retinitis pigmentosa with a specific FLVCR1 mutation.

BACKGROUND: Posterior column ataxia retinitis pigmentosa (PCARP) with feline leukemia virus subgroup C cellular receptor 1 (FLVCR1) gene mutation is a rare disorder with significant ophthalmic features. MATERIALS AND METHODS: We conducted a retrospective case series study of patients diagnosed with PCARP and genetic testing positive for FLVCR1 mutation between 1 January 2015 and 1 October 2017 at the Children's Hospital of Pittsburgh. Clinical charts, visual fields, fundus autofluorescence, and spectral-domain optical coherence tomography (SD-OCT) were reviewed. RESULTS: Seven patients from three families were identified to have PCARP and FLVCR1 mutation. The median age at presentation was 13 years (range, 7-28 years). Common clinical exam findings were astigmatism, cataracts, and vitreous syneresis. Funduscopy on all patients revealed bull's eye maculopathy, retinal vessels attenuation, and bone spicule changes in the peripheral retina. Fundus autofluorescence showed bilateral hyperautofluorescent rings. SD-OCT demonstrated morphological changes, which differed based on age. The youngest sibling family exhibited peripheral loss, but subfoveal preservation of the outer retinal layers. These layers were lost in the oldest sibling family. Visual fields loss paralleled SD-OCT findings. CONCLUSION: There is limited published ophthalmic data on FLVCR1-related PCARP. We describe clinical and retinal imaging features in the one of the largest cohorts of affected patients in the literature. Given the availability of genetic testing for this phenotype, testing for FLVCR1 mutations should be considered in pediatric and adult patients with sensory ataxia and retinitis pigmentosa.

Genome-wide association studies for corneal and refractive astigmatism in UK Biobank demonstrate a shared role for myopia susceptibility loci.

Previous studies have suggested that naturally occurring genetic variation contributes to the risk of astigmatism. The purpose of this investigation was to identify genetic markers associated with corneal and refractive astigmatism in a large-scale European ancestry cohort (UK Biobank) who underwent keratometry and autorefraction at an assessment centre. Genome-wide association studies for corneal and refractive astigmatism were performed in individuals of European ancestry (N = 86,335 and 88,005 respectively), with the mean corneal astigmatism or refractive astigmatism in fellow eyes analysed as a quantitative trait (dependent variable). Genetic correlation between the two traits was calculated using LD Score regression. Gene-based and gene-set tests were carried out using MAGMA. Single marker-based association tests for corneal astigmatism identified four genome-wide significant loci (P < 5 × 10-8) near the genes ZC3H11B (1q41), LINC00340 (6p22.3), HERC2/OCA2 (15q13.1) and NPLOC4/TSPAN10 (17q25.3). Three of these loci also demonstrated genome-wide significant association with refractive astigmatism: LINC00340, HERC2/OCA2 and NPLOC4/TSPAN10. The genetic correlation between corneal and refractive astigmatism was 0.85 (standard error = 0.068, P = 1.37 × 10-35). Here, we have undertaken the largest genome-wide association studies for corneal and refractive astigmatism to date and identified four novel loci for corneal astigmatism, two of which were also novel loci for refractive astigmatism. These loci have previously demonstrated association with axial length (ZC3H11B), myopia (NPLOC4), spherical equivalent refractive error (LINC00340) and eye colour (HERC2). The shared role of these novel candidate genes for astigmatism lends further support to the shared genetic susceptibility of myopia and astigmatism.

A genome-wide association study of corneal astigmatism: The CREAM Consortium.

Purpose: To identify genes and genetic markers associated with corneal astigmatism. Methods: A meta-analysis of genome-wide association studies (GWASs) of corneal astigmatism undertaken for 14 European ancestry (n=22,250) and 8 Asian ancestry (n=9,120) cohorts was performed by the Consortium for Refractive Error and Myopia. Cases were defined as having >0.75 diopters of corneal astigmatism. Subsequent gene-based and gene-set analyses of the meta-analyzed results of European ancestry cohorts were performed using VEGAS2 and MAGMA software. Additionally, estimates of single nucleotide polymorphism (SNP)-based heritability for corneal and refractive astigmatism and the spherical equivalent were calculated for Europeans using LD score regression. Results: The meta-analysis of all cohorts identified a genome-wide significant locus near the platelet-derived growth factor receptor alpha (PDGFRA) gene: top SNP: rs7673984, odds ratio=1.12 (95% CI:1.08-1.16), p=5.55×10-9. No other genome-wide significant loci were identified in the combined analysis or European/Asian ancestry-specific analyses. Gene-based analysis identified three novel candidate genes for corneal astigmatism in Europeans-claudin-7 (CLDN7), acid phosphatase 2, lysosomal (ACP2), and TNF alpha-induced protein 8 like 3 (TNFAIP8L3). Conclusions: In addition to replicating a previously identified genome-wide significant locus for corneal astigmatism near the PDGFRA gene, gene-based analysis identified three novel candidate genes, CLDN7, ACP2, and TNFAIP8L3, that warrant further investigation to understand their role in the pathogenesis of corneal astigmatism. The much lower number of genetic variants and genes demonstrating an association with corneal astigmatism compared to published spherical equivalent GWAS analyses suggest a greater influence of rare genetic variants, non-additive genetic effects, or environmental factors in the development of astigmatism.

Micrometric Control of the Optics of the Human Eye: Environment or Genes?

Purpose: The human eye has typically more optical aberrations than conventional artificial optical systems. While the lower order modes (defocus and astigmatism) are well studied, our purpose is to explore the influence of genes versus the environment on the higher order aberrations of the optical components of the eye. Methods: We have performed a classical twin study in a sample from the Region of Murcia (Spain). Optical aberrations using a Hartmann-Shack sensor (AOnEye Voptica SL, Murcia, Spain) and corneal aberrations (using corneal topography data) were measured in 138 eyes corresponding to 69 twins; 36 monozygotic (MZ) and 33 dizygotic (DZ) pairs (age 55 years, SD 7 years). Intraclass correlation coefficients (ICCs) were used to estimate how strongly aberrations of twins resemble each other, and genetic models were fitted to quantify heritability in the selected phenotypes. Results: Genes had a significant influence in the variance of most of the higher order aberration terms (heritability from 40% to 70%). This genetic influence was observed similarly in both cornea and complete eye aberrations. Additionally, the compensation factor of spherical aberration in the eye (i.e., how much corneal spherical aberration was compensated by internal spherical aberration) was found under genetic influence (heritability of 68%). Conclusions: There is a significant genetic contribution to the variance of aberrations of the eye, not only at macroscopic levels, as in myopia or astigmatism, but also at microscopic levels, where a few micrometers changes in surface topography can produce a large difference in the value of the optical aberrations.

Two Cases with Ring Chromosome 13 at either End of the Phenotypic Spectrum.

Ring chromosome 13 is a rare genetic condition with an incidence of 1/58,000 in live births. Major clinical features of patients with ring chromosome 13 include growth and developmental retardation, microcephaly, facial dysmorphism, ambiguous genitalia, anal atresia, eye malformations, retinoblastoma, and hand, foot, and toe abnormalities. The severity of the phenotype depends on the amount of genetic material lost during ring chromosome formation. Here, we report 2 cases with ring chromosome 13 at either end of the phenotypic spectrum.

Anisometropia of ocular refractive and biometric measures among 66- to 79-year-old female twins.

PURPOSE: To examine the prevalence of anisometropia of spherical refraction (AnisoSR), astigmatism (AnisoAST) and spherical equivalent (AnisoSE) and their associations with spherical refraction (SR), refractive astigmatism (AST), spherical equivalent (SE) and interocular differences of ocular biometric parameters among elderly female twins. METHODS: Refraction of 117 monozygotic (MZ) and 116 dizygotic (DZ) female twin subjects aged 66-79 years was assessed with an auto-refractor (Topcon AT) and controlled by subjective refraction. Corneal refraction, anterior chamber depth and axial length were measured with a Zeiss IOL Master. Participants with eyes operated for cataract or glaucoma were excluded, but the grade of nuclear opacity was not recorded. The associations between the absolute values of AnisoSR, AnisoAST and AnisoSE with SR, AST, SE, corneal refractive power (CR), corneal astigmatism (CAST), anterior chamber depth (ACD) and axial length (AL) and with their interocular differences were calculated. When calculating the interdependencies of the differences, the real and absolute differences between the right and left eye were used. RESULTS: Means ± standard deviations for AnisoSR, AnisoAST and AnisoSE were 0.67 ± 0.92 D, 0.42 ± 0.41 D and 0.65 ± 0.71 D, respectively. AnisoSR, AnisoAST and AnisoSE >1.0 D were present in 14.7%, 4.2% and 17.7% of cases, respectively. Anisometropia of spherical refraction (AnisoSR), AnisoAST and AnisoSE were higher the more negative the values of SR or SE. Hyperopic ametropia did not increase these anisometropia values. The correlations of AnisoSR and AnisoSE with the absolute values of interocular differences in CR and AL were non-significant. Using the real values of the interocular differences, the respective correlations were significant. The correlation between the real interocular differences in CR and AL was negative (r = -0.258, p < 0.001). Thus, the combined effect of the real interocular differences in CR and AL was a decrease in AnisoSR and AnisoSE (emmetropization). CONCLUSION: Higher AnisoSR and AnisoSE were associated with more myopic refraction and longer AL. Higher AnisoAST was associated with more negative SR and higher AST and CAST. The negative correlation between real interocular differences in CR and AL indicated their influence of emmetropization in AnisoSR and AnisoSE.

The genetic and environmental factors for keratoconus.

Keratoconus (KC) is the most common cornea ectatic disorder. It is characterized by a cone-shaped thin cornea leading to myopia, irregular astigmatism, and vision impairment. It affects all ethnic groups and both genders. Both environmental and genetic factors may contribute to its pathogenesis. This review is to summarize the current research development in KC epidemiology and genetic etiology. Environmental factors include but are not limited to eye rubbing, atopy, sun exposure, and geography. Genetic discoveries have been reviewed with evidence from family-based linkage analysis and fine mapping in linkage region, genome-wide association studies, and candidate genes analyses. A number of genes have been discovered at a relatively rapid pace. The detailed molecular mechanism underlying KC pathogenesis will significantly advance our understanding of KC and promote the development of potential therapies.

Estudio comparativo en queratoplastia para queratocono entre las técnicas lamelar profunda de Anwar (big bubble) y penetrante procedente de conversión / Comparative study of keratoconus between Anwar's deep anterior lamellar keratoplasty versus converted penetrating keratoplasty

OBJETIVO: El propósito de este grupo de estudio fue comparar los resultados entre los procedimientos de queratoplastia lamelar profunda anterior (deep anterior lamellar keratoplasty [DALK]) y queratoplastia penetrante (penetrating keratoplasty [PK]) en pacientes con queratocono. DISEÑO: Estudio de cohorte retrospectivo. MÉTODO: Se analizaron los resultados de 90 DALK y 49 PK procedentes de reconversión en pacientes con queratocono. Todos los procedimientos fueron realizados por el mismo cirujano (R.D.) desde 2006 hasta 2011. Entre ambos grupos se comparó la agudeza visual a distancia corregida (AVCC), el astigmatismo, el tiempo de la primera refracción, la paquimetría, el recuento de células endoteliales y las complicaciones postoperatorias. RESULTADOS: La media de edad fue de 28,2 años para DALK y de 31,7 años para PK (p = 0,17). El seguimiento medio fue de 14,7 meses para DALK y 19,4 meses para PK (p = 0,13). No hubo diferencia significativa alguna entre los grupos de PK y DALK en la media postoperatoria de AVCC (LogMAR) (0,17 frente a 0,17; p = 0,59), astigmatismo refractivo (-3,19 frente a -3,01 dioptrías; p = 0,65) ni en el tiempo de la primera refracción subjetiva (60,5 frente a 68 días; p = 0,50). Las principales complicaciones postoperatorias fueron 8% de rechazo endotelial en el grupo PK y 10% de vascularización de la interfaz en el grupo DALK. CONCLUSIONES: La única diferencia entre ambos grupos fue la neovascularización estromal profunda en DALK y el rechazo endotelial en PK, por lo que el procedimiento DALK debe ser considerado como primera opción en el tratamiento de pacientes con queratocono

OBJECTIVE: To compare outcomes between penetrating keratoplasty (PK) and deep anterior lamellar keratoplasty (DALK) in patients with keratoconus. DESIGN: Retrospective cohort study. METHODS: Data of 90 DALK and 49 procedures from conversion to PK, performed by a single surgeon (R.D.) from 2006 to 2011 were analysed. Outcomes on corrected distance visual acuity (BCVA), astigmatism, time to first refraction, pachymetry, endothelial count cell, and postoperative complications were compared between these groups. RESULTS: The mean age of the patients who underwent DALK and PK was 28.2 and 31.7 years, respectively (P=.17). The mean follow up for DALK and for the PK group was 14.7 and 19.4 months, respectively (P=.13). There was no significant difference between PK and DALK groups in the mean postoperative for: BCVA (LogMAR) (0.17 vs. 0.17; P=.59); refractive astigmatism (-3.19 vs.-3.01 diopters; P=.65), and time for the first subjective refraction (60.5 versus 68 days; P=.50). Main postoperative complications were 8% of endothelial rejection in PK group and 10% of deep stromal vascularization in DALK group. CONCLUSIONS: The only differences in postoperative results between groups were stromal neovascularization in DALK group and endothelial rejection in PK group. DALK should be considered as the first option when keratoplasty is indicated in keratoconus

Genome-wide association study for refractive astigmatism reveals genetic co-determination with spherical equivalent refractive error: the CREAM consortium.

To identify genetic variants associated with refractive astigmatism in the general population, meta-analyses of genome-wide association studies were performed for: White Europeans aged at least 25 years (20 cohorts, N = 31,968); Asian subjects aged at least 25 years (7 cohorts, N = 9,295); White Europeans aged <25 years (4 cohorts, N = 5,640); and all independent individuals from the above three samples combined with a sample of Chinese subjects aged <25 years (N = 45,931). Participants were classified as cases with refractive astigmatism if the average cylinder power in their two eyes was at least 1.00 diopter and as controls otherwise. Genome-wide association analysis was carried out for each cohort separately using logistic regression. Meta-analysis was conducted using a fixed effects model. In the older European group the most strongly associated marker was downstream of the neurexin-1 (NRXN1) gene (rs1401327, P = 3.92E-8). No other region reached genome-wide significance, and association signals were lower for the younger European group and Asian group. In the meta-analysis of all cohorts, no marker reached genome-wide significance: The most strongly associated regions were, NRXN1 (rs1401327, P = 2.93E-07), TOX (rs7823467, P = 3.47E-07) and LINC00340 (rs12212674, P = 1.49E-06). For 34 markers identified in prior GWAS for spherical equivalent refractive error, the beta coefficients for genotype versus spherical equivalent, and genotype versus refractive astigmatism, were highly correlated (r = -0.59, P = 2.10E-04). This work revealed no consistent or strong genetic signals for refractive astigmatism; however, the TOX gene region previously identified in GWAS for spherical equivalent refractive error was the second most strongly associated region. Analysis of additional markers provided evidence supporting widespread genetic co-susceptibility for spherical and astigmatic refractive errors.

Peripheral hypertrophic subepithelial corneal degeneration: characterization, treatment and association with human leucocyte antigen genes.

PURPOSE: To evaluate the efficacy of keratectomy in treating irregular astigmatism caused by peripheral hypertrophic subepithelial corneal degeneration (PHSD) and to study the possible underlying immunological risk factors. MATERIALS AND METHODS: Patients (14 eyes) with diagnosed PHSD were treated with superficial keratectomy with or without the assistance of phototherapeutic keratectomy (VisX S4; VisX Inc., Santa Ana, CA, USA). Thirteen patients were subjected to analysis of human leucocyte antigen (HLA) genes, complement C4 gene numbers and total plasma immunoglobulin levels. Immunological risk factors between patients and a control group comprising 150 individuals were compared. RESULTS: The mean preoperative best spectacle corrected visual acuity (BCVA) improved from 0.16 ± 0.22 (LogMAR scale range 0-0.7) to 0.06 ± 0.13 (-0.1-0.4) (p < 0.01). The mean preoperative astigmatism decreased significantly from 3.8 ± 2.1 D (range 1.2-8.2) to 2.1 ± 1.4 (range 0.6-5.0, p = 0.02) based on corneal topography. The HLA-B*44 allele and the ancestral haplotype (AH) 8.1 were found significantly more often in PHSD patients than in controls (both p = 0.03). No differences in the C4 genes were found. CONCLUSIONS: Astigmatism secondary to PHSD can be effectively treated with keratectomy. Peeling of the fibrotic tissue reduced astigmatism and improved visual performance. We suggest that HLA-B*44 allele and AH 8.1 haplotype are immunological factors predisposing to the development of PHSD. The consequent disruption/alteration of the limbal barrier may lead to corneal peripheral fibrous formation inducing astigmatism.

Heritability of refractive astigmatism: a population-based twin study among 63- to 75-year-old female twins.

PURPOSE: To examine the heritability of refractive astigmatism in older women. METHODS: Astigmatism was measured with an autorefractor in 88 monozygotic and 82 dizygotic female twin pairs aged 63 to 75 years. The prevalence and distribution of astigmatism and polar values J0 and J45 were estimated by standard statistical methods. Bivariate maximum likelihood model fitting was used to estimate genetic and environmental variance components using information from both eyes. RESULTS: Mean astigmatism of the more astigmatic eye was 0.93 diopters (D; SD ±0.58). Astigmatism of at least 0.25 D, 0.5 D, 0.75 D, or 1.0 D in either eye was present in 99.7%, 88.5%, 66.5%, and 46.2% of cases, respectively. The main direction of astigmatism was against the rule. The age-adjusted quantitative genetic modeling revealed that additive genetic effects accounted for 33.3% (95% confidence interval [CI], 21.9%-43.8%) of the total variance of astigmatism and for 18% (95% CI, 4%-31%) of the total variance of polar value J45 of both eyes (bivariate model), with the remaining variances due to nongenetic effects. There were no significant correlations between the twin pairs for polar value J0. CONCLUSIONS: In elderly female twins, additive genetic effects accounted for one-third of the variance of the amount of astigmatism and only a small fraction of the total variance of polar value J45.