Cataract Candidates Research Articles

Cataracts in Havanese: genome wide association study reveals two loci associated with posterior polar cataract

BackgroundCataract is considered an important health issue in Havanese, and studies indicate a breed predisposition. Possible consequences of cataracts include lens induced uveitis, reduced eyesight, and blindness in severe cases. Reducing the prevalence of cataracts could therefore improve health and welfare significantly. The most frequently diagnosed forms of cataract in Havanese are cortical- and anterior suture line cataract, but cases of posterior polar cataract are also regularly reported. Out of the three, posterior polar- and cortical cataracts are considered the most clinically relevant.ResultsWe performed a genome wide association study that included 57 controls and 27 + 23 + 7 cases of cortical-, anterior suture line- and posterior polar cataract, respectively. An association analysis using a mixed linear model, revealed two SNPs on CFA20 (BICF2S23632983, p = 7.2e-09) and CFA21 (BICF2G630640490, p = 3.3e-09), that were significantly associated with posterior polar cataract, both of which are linked to relevant candidate genes. The results suggest that the two variants are linked to alleles with large effects on posterior polar cataract formation, possibly in a dominant fashion, and identifies regions that should be subject to further sequencing.Promising regions on CFA4 and CF30 were also identified in the association analysis of cortical cataract. The top SNPs on each chromosome, chr4_12164500 (p = 4.3e-06) and chr30_28836339 (p = 5.6e-06), are located within, or in immediate proximity to, potential cataract candidate genes.The study shows that age at examination is strongly associated with sensitivity of cataract screening. Havanese in Norway are on average 3.4 years old when eye examinations are performed: an age where most dogs that are genetically at risk have not yet developed clinically observable changes. Increasing the average age of breeding animals could increase accuracy of selection, leading to improved health.ConclusionsThe study identified two loci, on CFA20 and CFA21, that were significantly associated with posterior polar cataract in Havanese. SNPs that showed putative association with cortical cataracts, were observed on CFA4 and CFA30. All the top SNPs are located in close proximity to cataract candidate genes. The study also show that sensitivity of cataract screening is highly dependent on age at examination.

Anterior chamber parameters in cataract surgery candidates from middle China.

To determine the distribution of the anterior chamber parameters and associated factors in cataractous adults from middle China. In this cross-sectional study, axial length, anterior chamber depth (ACD) and lens thickness (LT) were measured with IOLMaster 700. The Pentacam HR was designed to measure the anterior chamber volume (ACV) and anterior chamber angle (ACA). Patients' data were collected and analyzed between 2020 and 2022. A total of 157 eyes of 157 Chinese adults (mean age: 64.43 ± 12.16 years) with a cataract were enrolled in this study. The mean values measured were as follows: axial length, 24.10 ± 2.44mm; ACD, 2.99 ± 0.52 mm; LT, 4.51 ± 0.48 mm; ACV, 113.98 ± 45.12 mm3; ACA, 32.33 ± 7.66 degrees. The ACD and ACV were statistically significantly greater in men than in women and had a decrease trend as age and LT increased. In the simulated linear equation of age with ACD and LT the absolute slope coefficients of equations were the same; however, the directions were opposite. The mean ACV was <100 mm3 when the patients were over 60 years. In the multivariate regression analysis of ACD, ACV and ACA there was a reasonable prediction with adjusted R2 = 0.878, 0.847 and 0.564, respectively. This study may provide normative data for cataract patients. The profile of anterior chamber can help improve the knowledge of the risk of angle closure in cataract candidates.

Visual Performance and Quality of Life after Femtosecond Laser-Assisted Cataract Surgery with Trifocal IOLs Implantation.

Purpose: To assess visual performance and quality of life after implantation of diffractive trifocal IOLs with enhanced depth of focus (Acriva Reviol Tri-ED) compared to monofocal IOLs. Setting: Ophthalmology Clinic, Department of Medicine and Science of Ageing, University “G. d’Annunzio” Chieti-Pescara, Italy. Design: Prospective clinical study. Methods: This study comprised 36 eyes of 18 patients with senile cataract candidates for phacoemulsification and implantation of the Acriva Reviol Tri-ED (Group 1–18 eyes) and the AcrySof IQ Monofocal IOL SN60WF (Group 2–18 eyes). The main outcome measures, over a 6-month follow-up period, were uncorrected and corrected visual acuity at different distances (40, 60 cm and 4 m), defocus curve, contrast sensitivity and wavefront error. Patient satisfaction was evaluated by means of the NEI-RQL-42 questionnaire. Results: At 180 days postoperatively, the difference of the UCDVA and CDVA between the groups was not statistically significant (p = 0.888 and p = 0.843, respectively). The difference between the groups was statistically significant for UCIVA (p = 0.019) and UCNVA (p = 0.036). The mean values of contrast sensitivity under photopic and mesopic conditions were not significantly different between the groups. The RMS of spherical aberration was significantly lower in Group 1 compared to Group 2. The NEI-RQL-42 questionnaire showed statistically significant differences between the groups for the dependence on correction (p < 0.001). Conclusions: The diffractive trifocal IOL with enhanced depth of focus Acriva Reviol Tri-ED was effective in improving functional capacity for intermediate and near vision compared to monofocal IOLs and provided a good quality of vision due to a significant reduction in spherical aberration.

Rapid and efficient cataract gene evaluation in F0 zebrafish using CRISPR-Cas9 ribonucleoprotein complexes.

Cataract is the leading cause of blindness worldwide. Congenital or paediatric cataract can result in permanent visual impairment or blindness even with best attempts at treatment. A significant proportion of paediatric cataract has a genetic cause. Therefore, identifying the genes that lead to cataract formation is essential for understanding the pathological process of inherited paediatric cataract as well as to the development of new therapies. Despite clear progress in genomics technologies, verification of the biological effects of newly identified candidate genes and variants is still challenging. Here, we provide a step-by-step pipeline to evaluate cataract candidate genes in F0 zebrafish using CRISPR-Cas9 ribonucleoprotein complexes (RNP). Detailed descriptions of CRISPR-Cas9 RNP design and formulation, microinjection, optimization of CRISPR-Cas9 RNP reagent dose and delivery route, editing efficacy analysis as well as cataract formation evaluation are included. Following this protocol, any cataract candidates can be readily and efficiently evaluated within 2weeks using basic laboratory supplies.

Comparison of Ocular Biometry Profiles in Urban and Rural Cataract Candidates in Eastern China.

Purpose To compare ocular biometric parameters between urban and rural cataract patients in Shanghai, China. Methods A study of ocular biometry records from urban and rural hospitals was performed for cataract patients at least 50 years of age. The ocular biometrical parameters, which were measured with partial coherence laser interferometry (IOL Master, Zeiss), were axial length (AL), anterior chamber depth (ACD), radius of corneal curvature (K, including steep/flat/average K), astigmatism, and axis. Only the right eye record of each patient was analysed. Results Ocular biometric data included 2839 urban patients (73.15 ± 9.54 years) and 2646 rural patients (73.64 ± 7.32 years). Mean AL, ACD, and K were 24.35 ± 2.34 mm, 3.14 ± 0.58 mm, and 44.38 ± 1.52 D, respectively, in urban patients and 23.58 ± 1.70 mm, 3.08 ± 0.57 mm, and 44.53 ± 1.50 D, respectively, in rural patients. The urban subjects had significantly longer axial lengths (in both univariate and multivariate linear regression analyses) and deeper ACDs (in univariate analysis) than rural subjects (p < 0.01). There was no significant difference in steep K, flat K, and average K between the two groups. With-the-rule (WTR) corneal astigmatism was found in 1787 eyes (32.58%), against-the-rule (ATR) corneal astigmatism was found in 2727 eyes (49.72%), and oblique corneal astigmatism was found in 971 eyes (17.70%). Conclusions We report biometry and astigmatism data in a large cohort of urban and rural adult subjects for the first time. In our study, a short AL, shallow ACD, and axis turned in an ATR direction had higher prevalence rates in the rural subjects. This profile of ocular biometric data and corneal astigmatism will be helpful in planning for intraocular lens (IOL) power calculations and astigmatism correction in subjects in different locations.

Studies of congenital cataract-related TSR1 mutation and its expression in the lens.

Congenital cataract (CC) is a rare disease with dysplasia of the lens, mainly characterized by partial or complete opacity of the lens. The molecular basis of the disease is complex, mutations in over 266 genes associated with congenital cataracts had been reported. In this study, a novel congenital cataract candidate gene TSR1 was identified by whole genome sequencing and Sanger sequencing in a Chinese congenital cataract family. The TSR1 c.202-1G>A substitution affected splicing of TSR1 mRNA was confirmed by a minigene assay. The expression of TSR1 in mouse lens, anterior lens capsule of age-related cataract patients and 24-week human fetal lens were determined by RT-PCR, Western blotting, and immunofluorescence assays. The expression of TSR1 in the embryonic and different developmental stages of the mouse lens was confirmed by analyzing the iSyTE database. The expression of TSR1 was down-regulated in the lens-specific CBP:p300 double knockout mouse, and a set of genes with the same expression pattern of Tsr1 in the CBP:p300 double knockout mouse lens were extracted for protein-protein interaction network analysis, and six proteins were screened for direct interaction with Tsr1. GO function analysis indicated that Tsr1 might play a role in the MAPK-Erk signaling pathway in addition to its involvement in ribosome assembly. This study provided valuable research clues to further clarify the function of Tsr1 in the lens.

Diabetes and diabetic retinopathy in patients undergoing cataract surgery: a prevalence study-DiCat study report #2.

To report on the prevalence of diabetes, diabetic macula oedema (DME) and retinopathy and their respective grading in a large cohort of patients undergoing cataract surgery. Data on previous diagnosis of diabetes, fasting glucose, glycated haemoglobin, presence and type of retinopathy and other maculopathy of 3657 patients over 55years of age undergoing cataract surgery in 13 centres scattered throughout Italy were analysed. A total of 20.4% of patients were known diabetics and 27.9% of diabetics showed signs of retinopathy. Haemoglobin A1C was higher than 48mmol/L (6.5%) in 32% of diabetics and 2.4% non-diabetics. Fasting blood glucose level was higher than 120mg/dL in 4.3% non-diabetics and 50% diabetics. Duration of diabetes did not significantly correlate with either fasting glucose or glycated haemoglobin, while higher grades of diabetic retinopathy were significantly more prevalent as duration of disease increased. DME was present in almost 40% of diabetics and 22% of patients showed non-diabetic maculopathy. Diabetic retinopathy and DME worsen after cataract extraction thus complicating long-term prognosis and requiring expensive injective therapy. Since unknown diabetics represent 2-4% of the many million cataract candidates and even known diabetics show poor metabolic control and high rates of DME, preoperative medical testing and accurate retinopathy screening may prove both ethically necessary and cost-effective.

Analysis of corneal astigmatism with NIDEK axial length scan in caucasian cataract surgery candidates.

The aim of the study was to analyze and quantify the pattern of corneal astigmatism in Caucasian cataract surgery patients using a new optical biometer (axial length [AL] Scan, NIDEK Co., Gamagori, Japan). The datasets of cataract surgery patients acquired between March 1, 2014, and April 15, 2016, were collected and analyzed. The corneal power (flat keratometry, steep keratometry, and mean keratometry), negative cylinder power, and axis of astigmatism were recorded. Keratometry values were optically measured by optical low coherence interferometry (AL-Scan, NIDEK Co., Ltd.,) before cataract extraction. The study comprised 1233 eyes of 838 consecutive cataract candidates with a mean age of 66.8 ± 10.7 years (range 40-97 years). The mean keratometry value and corneal astigmatism were 43.69 ± 1.61 D and 0.84 ± 0.70 D, respectively. Corneal astigmatism of 1.00 D or greater was found in 344 eyes (27.9%), and 548 eyes (44.4%) had against-the-rule astigmatism. A trend toward decreasing J0 and J45 with age was found by linear regression models. The per-year increase in age was associated with a J0 and J45 decrease of 0.002 D and 0.001D, respectively. This study provides the distribution of astigmatism axis and power for cataract patients in age subsets from Turkey.

Lenstar LS 900 Analysis of 2000 Cataract Patients: A Cross-Sectional Study

Purpose: To analyze biometry data and corneal astigmatism in cataract candidates from Yazd. Methods: The corneal thickness, anterior chamber depth and keratometry measurements of anteroposterior width were measured using the IOL Master system. Ocular biometric data were collected and analyzed in the year 2015. Results: The study comprised of 2000 patients' cataract candidates with a mean age of 66.79 ± 10.72 years (range 28 to 100 years). No significant differences were found between these variables for mean ± SDs of age and gender (p<0.05). The correlation coefficients analysis between four evaluated variables and age showed there is a significant correlation between anterior chamber depth and age; however, there was no association between age and other factors. Also, the results showed a significant correlation between the radius of cornal curvature, anterior chamber depth, corneal thickness and anterior-posterior length. Conclusions: This study provides reference data for cataract patients from Yazd. The profiles of ocular biometric data can help improve surgical procedures and intraocular lens design for the Yazd population.

Biometry and corneal astigmatism in cataract surgery candidates from Southern China

To analyze biometry data and corneal astigmatism in cataract candidates from Southern China. Guangdong Eye Institute, Guangdong General Hospital, Guangzhou, China. Cross-sectional hospital-based study. The axial length (AL), anterior chamber depth (ACD), horizontal corneal diameter (white to white [WTW]), and corneal power (keratometry [K], flat K, steep K) were measured using the IOLMaster system. Ocular biometric data were collected and analyzed between 2007 and 2011. The study comprised 6750 eyes of 4561 consecutive cataract candidates with a mean age of 70.4 years ± 10.5 (SD). The mean AL, ACD, and WTW were 24.07 ± 2.14 mm, 3.01 ± 0.57 mm, and 11.68 ± 0.45 mm, respectively. All values were statistically significantly greater in men than in women (P < .001) and had a significant trend toward a decrease as age increased (P < .001). The mean K value was 44.13 ± 1.63 D. The median corneal astigmatism was 0.90 D (interquartile range, 0.54-1.43). Corneal astigmatism of 1.00 D or greater was found in 2963 eyes (43.9%), and 3590 eyes (53.2%) had against-the-rule (ATR) astigmatism. The axis of corneal astigmatism turned in the ATR direction with age. This study provides reference data for cataract patients from Southern China. The profiles of ocular biometric data and corneal astigmatism can help improve surgical procedures and intraocular lens design for the Chinese population. No author has a financial or proprietary interest in any material or method mentioned.

Attention to the research about congenital cataract candidate gene

Congenital cataracts is the leading cause of visual disability in children worldwide.With the evolution of molecular biological technique,the researches of inherited congenital cataract mainly focus on localization and fuction characterization of the disease-associated gene,including crystallin,connexin,major intrinsic protein gene,etc.And great progress has been made for such genes in eye development,age-related cataract,epigenetics study.Thus,great attention must be paid to the functional research about congenital cataract candidate gene. Key words: Congenital cataract; Gene mutation; Crystallin; Connexin; Major intrinsic protein; Epigenetics

Development of Feline Microsatellites and SNPs for Evaluating Primary Cataract Candidate Genes as Cause for Cataract in Angolan Lions (Panthera leo bleyenberghi)

Primary cataracts (CAT) are characterized as any form of opacities of the eye lenses and are not accompanied by other diseases. CAT may impair vision depending on their size, location, and their state of progression. In order to investigate the cause of congenital or juvenile CAT in inbred Angolan lions kept in German zoos, we analyzed the genomic sequences of 4 crystalline genes CRYAA, CRYAB, CRYBB2, and CRYBB1. In addition, 10 CAT candidate genes (GJA3, LIM2, CRYGA, CRYGB, CRYGC, CRYGD CRYGS, BFSP2, CRYBA4, and CRYBB1) were analyzed using adjacent microsatellites. We identified 10 single nucleotide polymorphisms in the Angolan lion crystalline genes and 9 segregating microsatellites. Nonparametric and parametric linkage analyses did not reveal any linkage between one of the analyzed markers and CAT. So, we concluded that these genes can be excluded as causative for the familial primary cataract phenotype in these Angolan lions.

Analysis on gene mutations in a Chinese pedigree with autosomal dominant inheritance cataract

The aim of this study was to reveal the genetic defect of the autosomal dominant inheritance cataract in a Chinese pedigree. Case-control study. There were 26 individuals investigated with clinical examination in a Chinese four generations pedigree. The genome DNA of the individuals was extracted by the improved NaI method. The exons of six cataract candidate genes in 204 normal controls and 42 senile cataract patients were screened for the mutation by PCR restriction fragment length polymorphism (PCR-RFLP) methods. The phenotype of the cataract was pulverulent nuclear cataract. A novel C/T transition at nucleotide position 827 was identified in the GJA8 gene that led to a serine to phenylalanine change in codon 276. This mutation was not found in 42 senile cataract patients and in 204 controls. Four single nucleotide polymorphisms (SNPs) were also found in a cataract candidate gene in the family members. A novel GJA8 gene mutation was found in a Chinese autosomal dominant inheritance cataract pedigree. A substitution, C276T in GJA8 gene, was identified as the most likely causative mutation underlying the phenotype of pulverulent nuclear cataract in all affected family members.

Quality of life assessment in children with congenital bilateral cataract

To study the influence of congenital bilateral cataract on visual-related quality of life (QoL) in children. The scale of QoL for children with congenital bilateral cataract was used to evaluate the QoL of 81 children with congenital bilateral cataract and 28 healthy children with normal visual acuity. The average age of congenital bilateral cataract candidates was 9.8 years (from 8 to 15 years) and 37 patients were female. Thirty-six cataract children took part in the both preoperative and postoperative investigations. The patients' QoL were also categorized by age, gender, score, visual acuity, surgery and density of cataract. Multiple-linear regression model was applied to analyze the influence factors of QoL. Statistically significant difference was found at the QoL between healthy children and children with congenital bilateral cataract (P = 0.00). The QoL in children with non-dense cataract was increased after cataract surgery (P = 0.00). A high correlation was found between visual acuity and QoL (r = 0.53, P = 0.00). A statistically significant difference was found in QoL between dense and non-dense cataract (P = 0.00). Three variances enrolled in the multiple-linear regression equation included the density of cataract, surgery and visual acuity. Their partial regression coefficients were 6.14 (P = 0.00), 3.21 (P = 0.01) and 1.07 (P = 0.01) respectively. Compared with the healthy children, the QoL score was severely impaired in children with congenital bilateral cataract, which was influenced by the density of cataract, surgery and visual acuity. Visual acuity is the most critical factor influencing the QoL.

Genetic Heterogeneity in Microcornea-Cataract: Five Novel Mutations inCRYAA,CRYGD, andGJA8

To unravel the molecular genetic background in families with congenital cataract in association with microcornea (CCMC, OMIM 116150). CCMC families were recruited from a national database on hereditary eye diseases; DNA was procured from a national gene bank on hereditary eye diseases and by blood sampling from one large family. Genomewide linkage analysis, fine mapping, and direct genomic DNA sequencing of nine cataract candidate genes were applied. Restriction enzyme digests confirmed identified mutations. Analyses of 10 Danish families with hereditary congenital cataract and microcornea revealed five novel mutations. Three of these affected the crystallin, alpha-A gene (CRYAA), including two mutations (R12C and R21W) in the crystallin domain and one mutation (R116H) in the small heat shock domain. One mutation (P189L) affected the gap junction protein alpha 8 (GJA8), and one mutation (Y134X) was detected in crystallin gamma-D (CRYGD). The identification of a CRYGD mutation adds another gene to those that may be mutated in CCMC and underscores the genetic heterogeneity of this condition. Three CRYAA mutations at the R116 position, in association with CCMC, suggest that R116 represents a CCMC-mutational hotspot. The CCMC phenotype demonstrates variable expression with regard to cataract morphology and age of appearance. Clinical heterogeneity, including additional malformation of the anterior segment of the eye, confirm that dedicated cataract genes may be involved in the largely unknown developmental molecular mechanisms involved in lens-anterior segment interactions.

A novel mutation in the DNA‐binding domain of MAF at 16q23.1 associated with autosomal dominant “cerulean cataract” in an Indian family

Congenital cataract, a clinically and genetically highly heterogeneous eye disorder, is one of the significant causes of visual impairment or blindness in children. It is frequently inherited as an autosomal dominant trait. We investigated a three-generation family of Indian origin with 12 members affected with cerulean cataract. Linkage analysis was carried out in this family using more than 100 microsatellite markers for the known cataract candidate gene loci. A positive two-point lod score of 3.9 at theta = 0.000, indicative of linkage, was obtained with three microsatellite markers for chromosome 16. Multipoint and haplotype analysis narrowed the cataract locus to a 15.3 cM region between markers D16S518 and D16S511 that corresponds to the region 16q23.1. Direct sequencing of the candidate gene MAF, which lies in the critical linked region, revealed a novel heterozygous missense mutation in the basic region (BR) of the DNA-binding domain. This sequence change was considered pathogenic as it segregated in all affected family members, neither seen in unaffected family members nor in 106 unrelated controls. The mutation also results in substitution of highly conserved lysine 297 by arginine (K297R) that affects a residue that forms a part of a predicted DNA-interaction region of the protein. The association of microcornea with congenital cataract in some affected individuals further underlines the role of the MAF transcription factor in lens and anterior ocular development. Our findings expand the mutation spectrum of MAF in association with congenital cataract and highlight the genetic and phenotypic heterogeneity of congenital cataract.