Effects of cataract surgery and intra-ocular lens implantation on visual function and quality of life in age-related cataract patients: a systematic review protocol.
ABSTRACT: BACKGROUND:Cataract is the leading cause of blindness and low vision worldwide. Presently, cataract surgery is the only treatment for cataract and is very effective in restoring sight. In cataract surgery, the natural lens of the eye that becomes clouded is removed and replaced with an artificial intraocular lens. There are multiple techniques for removal of lens as well as many types of intraocular lenses available for implantation. For this reason, it becomes imperative to monitor the impact of different surgical techniques and different intraocular lenses on health-related quality of life (HRQoL) of the patients. This systematic review aims to evaluate HRQoL evidences on effects of different types of cataract surgeries and intraocular lenses on visual function and quality of life in age-related cataract patients. METHOD:Databases like Cochrane, EMBASE, SCOPUS, NHS Economic Evaluation Database (NHS EED), Health Technology Assessment (HTA) database, MEDLINE, ClinicalTrials.gov , Current Controlled Trials and World Health Organization International Clinical Trials Registry Platform (WHO ICTRP) will be searched systematically. Two reviewers will independently screen studies using predefined inclusion and exclusion criteria along with the extraction of data, and assessment of methodological quality using a standard checklist. DISCUSSION:This systematic review will help in understanding how different types of cataract surgeries and intraocular lenses make a difference on quality of life of age-related cataract patients in terms of visual function and health-related quality of life. As the review attempts to bring together all the cataract-related HRQoL evidences pertaining to different cataract surgical techniques, different intraocular lenses and cataract-related complications, it will also identify gaps in evidence. SYSTEMATIC REVIEW REGISTRATION:PROSPERO CRD42018092377.
Project description:Posterior capsular opacification (PCO) is a common long-term complication of cataract surgery. Intraocular lens design and material have been implicated in influencing the development of PCO. This study evaluated the association of hydrophobic and hydrophilic intraocular lenses on preventing PCO.Medline, Cochrane, EMBASE, and Google Scholar databases were searched until August 3, 2016, using the following search terms: cataract, posterior capsule opacification, and intraocular lens. Eligible studies included randomized controlled trials (RCTs), retrospective, and cohort studies.Eleven studies were included in the study with a total of 889 eyes/patients. The overall analysis revealed that hydrophobic intraocular lenses were associated with lower Nd:YAG laser capsulotomy rates than hydrophilic lenses [odds ratio (OR)?=?0.38, 95% confidence interval (95% CI)?=?0.16-0.91, P?=?.029]. Hydrophobic intraocular lenses were also associated with lower subjective PCO score (diff. in means: -1.32, 95% CI?=?-2.39 to -0.25, P?=?.015) and estimated PCO score (diff. in means: -2.23; 95% CI, -3.80 to -0.68, P?=?.005) as compared with hydrophilic lenses. Objective PCO score was similar between lens types. (diff. in means: -0.075; 95% CI, -0.18 to 0.035; P?=?.182). Pooled analysis found that visual acuity was similar between hydrophobic and hydrophilic intraocular lenses (diff. in means: -0.016; 95% CI, -0.041 to 0.009, P?=?.208).In general, PCO scores and the rate of Nd:YAG laser capsulotomy were influenced by intraocular lens biomaterial. Lens made of hydrophobic biomaterial were overall superior in lowering the PCO score and the Nd:YAG laser capsulotomy rate, but not visual acuity.
Project description:Rhegmatenous retinal detachment (RRD) is one of the most serious complications after phacoemulsification combined with intraocular lens implantation surgery. It has been reported that vision-related quality of life (VRQoL), as well as visual acuity rapidly decreased when RRD developed. However, little is known of the VRQoL in those RRD patients after anatomical retinal re-attachment, especially whether or not the VRQoL is higher than that before cataract surgery. In this prospective case series study, we use the Chinese-version low vision quality of life questionnaire (CLVQOL) to assess the changes of VRQoL in age-related cataract patients who suffered from RRD after phacoemulsification with intraocular lens (phaco-IOL) implantation. All participants were asked to complete questionnaires in face- to-face interviews one day before and two weeks after cataract surgery, as well as one day before and three months after RRD surgery. A total of 10,127 consecutive age-related cataract patients were followed up to one year after phaco-IOL implantation; among these patients, 17 were diagnosed as RRD. The total CLVQOL scores and subscale scores except "Mobility" decreased significantly when RRD developed. After retinal surgery, only the score of "General vision and lighting" in the CLVQOL questionnaires improved when compared to the scores two weeks after cataract surgery, although the best corrected visual acuity of all patients significantly raised up. However, the mean CLVQOL scores and subscale scores were still considerably higher than the level prior to cataract surgery. Our study suggests that cataract patients at high risk of postoperative RRD should not deny the opportunity to undergo phaco-IOL implantation, even though potential VRQoL impairment induced by RRD exists.
Project description:Post-translational modifications in lens proteins are key causal factors in cataract. As the most abundant post-translational modification in the lens, racemization may be closely related to the pathogenesis of cataract. Racemization of αA-crystallin, a crucial structural and heat shock protein in the human lens, could significantly influence its structure and function. In previous studies, elevated racemization from l-Asp 58 to d-isoAsp58 in αA-crystallin has been found in age-related cataract (ARC) lenses compared to normal aged human lenses. However, the role of racemization in high myopic cataract (HMC), which is characterized by an early onset of nuclear cataract, remains unknown. In the current study, apparently different from ARC, significantly increased racemization from l-Asp 58 to d-Asp 58 in αA-crystallin was identified in HMC lenses. The average racemization rates for each Asp isoform were calculated in ARC and HMC group. In ARC patients, the conversion of l-Asp 58 to d-isoAsp 58, up to 31.89%, accounted for the main proportion in racemization, which was in accordance with the previous studies. However, in HMC lenses, the conversion of l-Asp 58 to d-Asp 58, as high as 35.44%, accounted for the largest proportion of racemization in αA-crystallin. The different trend in the conversion of αA-crystallin by racemization, especially the elevated level of d-Asp 58 in HMC lenses, might prompt early cataractogenesis and a possible explanation of distinct phenotypes of cataract in HMC.
Project description:Mutations in the human phosphatase and tensin homolog (PTEN) gene cause PTEN hamartoma tumor syndrome (PHTS), which includes cataract development among its diverse clinical pathologies. Currently, it is not known whether cataract formation in PHTS patients is secondary to other systemic problems, or the result of the loss of a critical function of PTEN within the lens. We generated a mouse line with a lens-specific deletion of Pten (PTEN KO) and identified a regulatory function for PTEN in lens ion transport. Specific loss of PTEN in the lens resulted in cataract. PTEN KO lenses exhibited a progressive age-related increase in intracellular hydrostatic pressure, along with, increased intracellular sodium concentrations, and reduced Na+/K+-ATPase activity. Collectively, these defects lead to lens swelling, opacities and ultimately organ rupture. Activation of AKT was highly elevated in PTEN KO lenses compared to WT mice. Additionally, pharmacological inhibition of AKT restored normal Na+/K+-ATPase activity in primary cultured lens cells and reduced lens pressure in intact lenses from PTEN KO animals. These findings identify a direct role for PTEN in the regulation of lens ion transport through an AKT-dependent modulation of Na+/K+-ATPase activity, and provide a new animal model to investigate cataract development in PHTS patients.
Project description:The Emory mouse is a well-characterized model for age-onset cataract. The purpose of the present study was to identify differentially expressed genes between pre- and postcataract Emory mouse lenses.Eyes were extracted from Emory mice at 3 weeks (precataract) and 7.5 months (postcataract) of age, and lenses were dissected. Lens RNA was compared for gene expression differences by RT-PCR differential display, and transcripts exhibiting altered levels of gene expression were cloned and identified by sequencing. The levels of two transcripts were further evaluated by RT-PCR in 3-week- and 7.5-month-old lenses and the remainder of the eye. The same transcripts were also measured in lenses from three non-Emory mouse strains (FVB/N, 129Sv, and CD1) ages 4 weeks to 11.5 months.Three transcripts were identified as exhibiting altered levels of gene expression between 3-week- and 7.5-month-old Emory mouse lenses. These encoded alphaA-crystallin (decreased), betaA3/A1-crystallin (decreased), and adhesion-related kinase (ARK) receptor tyrosine kinase (increased). Decreased alphaA-crystallin and increased ARK expression were not detected in lenses isolated from three non-Emory mouse strains of similar age. Increased expression of ARK was not detected between 3-week- and 7.5-month-old Emory mouse eye nonlens tissues.The present data confirm that expression of the alphaA-crystallin gene is decreased in cataract in the Emory mouse lens relative to age-matched control lenses and they provide evidence for cataract- and lens-specific upregulation of the ARK receptor tyrosine kinase in the Emory mouse.
Project description:The accumulation of crystallin fragments in vivo and their subsequent interaction with crystallins are responsible, in part, for protein aggregation in cataracts. Transgenic mice overexpressing acylpeptide hydrolase (APH) specifically in the lens were prepared to test the role of protease in the generation and accumulation of peptides. Cataract development was seen at various postnatal days in the majority of mice expressing active APH (wt-APH). Cataract onset and severity of the cataracts correlated with the APH protein levels. Lens opacity occurred when APH protein levels were >2.6% of the total lens protein and the specific activity, assayed using Ac-Ala-p-nitroanilide substrate, was >1 unit. Transgenic mice carrying inactive APH (mt-APH) did not develop cataract. Cataract development also correlated with N-terminal cleavage of the APH to generate a 57-kDa protein, along with an increased accumulation of low molecular weight (LMW) peptides, similar to those found in aging human and cataract lenses. Nontransgenic mouse lens proteins incubated with purified wt-APH in vitro resulted in a >20% increase in LMW peptides. Crystallin modifications and cleavage were quite dramatic in transgenic mouse lenses with mature cataract. Affected lenses showed capsule rupture at the posterior pole, with expulsion of the lens nucleus and degenerating fiber cells. Our study suggests that the cleaved APH fragment might exert catalytic activity against crystallins, resulting in the accumulation of distinct LMW peptides that promote protein aggregation in lenses expressing wt-APH. The APH transgenic model we developed will enable in vivo testing of the roles of crystallin fragments in protein aggregation.
Project description:Purpose:Cataract, a clouding of the intraocular lens, is the leading cause of blindness. The lens-expressed long noncoding RNA OIP5-AS1 was upregulated in lens epithelial cells from patients with cataracts, suggesting its pathogenic role in cataracts. We investigated the regulatory role of OIP5-AS1 in the development of cataracts as well as potential RNA binding proteins, downstream target genes, and upstream transcription factors. Methods:Clinical capsules and ex vivo and in vitro cataract models were used to test OIP5-AS1 expression. Cell apoptosis was detected using Western blots, JC-1 staining, and flow cytometry. Ribonucleoprotein immunoprecipitation-qPCR was performed to confirm the interaction of OIP5-AS1 and POLG. Chromatin immunoprecipitation-qPCR was used to determine the binding of TFAP2A and the OIP5-AS1 promoter region. Results:OIP5-AS1 was upregulated in cataract lenses and B3 cells under oxidative stress. OIP5-AS1 knockdown protected B3 cells from H2O2-induced apoptosis and alleviated lens opacity in the ex vivo cataract model. HuR functioned as a scaffold carrying OIP5-AS1 and POLG mRNA and mediated the decay of POLG mRNA. POLG was downregulated in the cataract lens and oxidative-stressed B3 cells, and POLG depletion decreased the mtDNA copy number and MMP, increased reactive oxygen species production, and sensitized B3 cells to oxidative stress-induced apoptosis. POLG overexpression reversed these effects. TFAP2A bound the OIP5-AS1 promoter and contributed to OIP5-AS1 expression. Conclusions:We demonstrated that OIP5-AS1, activated by TFAP2A, contributed to cataract formation by inhibiting POLG expression mediated by HuR, thus leading to increased apoptosis of lens epithelial cells and aggravated lens opacity, suggesting that OIP5-AS1 is a potential target for cataract treatment.
Project description:Age-related cataract is a multi-factorial disease with a poorly understood etiology. Numerous studies provide evidence that the human eye lens has evolved specific regulatory and protective systems to ameliorate lens damage associated with cataract. Other studies suggest that the presence of cataract is associated with the altered expression of specific genes including metallothionein IIa, osteonectin, transglutaminase 2, betaig-h3, multiple ribosomal proteins, ADAM9, and protein phosphatase 2A. Here, we sought to identify further gene expression changes that are associated with cataract and to cluster the identified genes into specific biological pathways.Oligonucleotide microarray hybridization was used to analyze the full complement of gene expression differences between lens epithelia isolated from human age-related cataract relative to clear lenses. The expression levels of a subset of the identified genes were further evaluated by semi-quantitative RT-PCR. The identified genes were functionally clustered into specific categories and the probability of over-representation of each category was determined using the computer program EASE.412 transcripts were observed to be increased and 919 transcripts were observed to be decreased by 2 fold or more in lens epithelia isolated from age-related cataract relative to clear lenses. Of these, 74 were increased and 241 were decreased at the 5 fold level or greater. Seventeen genes selected for further confirmation exhibited similar trends in expression when examined by RT-PCR using both the original and separately prepared clear and cataract RNA populations. Functional clustering of the identified genes using the EASE bioinformatics software package revealed that, among others, transcripts increased in cataract are associated with transcriptional control, chromosomal organization, ionic and cytoplasmic transport, and extracellular matrix components while transcripts decreased in cataract are associated with protein synthesis, defense against oxidative stress, heat-shock/chaperone activity, structural components of the lens, and cell cycle control.These data suggest that cataract is associated with multiple previously identified and novel changes in lens epithelial gene expression and they point to numerous pathways likely to play important roles in lens protection, maintenance, and age-related cataract.
Project description:Long-lived proteins are widespread in man, yet little is known about the processes that affect their function over time, or their role in age-related diseases.Racemization of two proteins from normal and cataract human lenses were compared with age using tryptic digestion and LC/mass spectrometry. Asp 151 in ?A crystallin and Asn 76 in ?S crystallin were studied.Age-dependent profiles for the two proteins from normal lenses were different. In neither protein did the modifications increase linearly with age. For ?A crystallin, racemization occurred most rapidly during the first 15 years of life, with approximately half of L-Asp 151 converted to D-isoAsp, L-isoAsp, and D-Asp in a ratio of 3:1:0.5. Values then changed little. By contrast, racemization of Asn 76 in ?S crystallin was slow until age 15, with isoAsp accounting for only 5%. Values remained relatively constant until age 40 when a linear increase (1%/year) took place. When cataract lenses were compared with age-matched normal lenses, there were marked differences in the time courses of the two crystallins. For ?A crystallin, there was no significant difference in Asp 151 racemization between cataract and normal lenses. By contrast, in ?S crystallin the degree of conversion of Asn 76 to isoAsp in cataract lenses was approximately double that of normals at every age.Modification of Asn and Asp over time may contribute to denaturation of proteins in the human lens. An accelerated rate of deamidation/racemization at selected sites in proteins, such as ?S crystallin, may contribute to cataract formation.
Project description:The Shumiya cataract rat (SCR) is a model for hereditary cataract. Two-thirds of these rats develop lens opacity within 10-11 weeks. Onset of cataract is attributed to the synergetic effect of lanosterol synthase (Lss) and farnesyl-diphosphate farnesyltransferase 1 (Fdft1) mutant alleles that lead to cholesterol deficiency in the lenses, which in turn adversely affects lens biology including the growth and differentiation of lens epithelial cells (LECs). Nevertheless, the molecular events and changes in gene expression associated with the onset of lens opacity in SCR are poorly understood. In the present study, a microarray-based approach was employed to analyze comparative gene expression changes in LECs isolated from the precataractous and cataractous stages of lenses of 5-week-old SCRs. The changes in gene expression observed in microarray results in the LECs were further validated using real-time reverse transcribed quantitative PCR (RT-qPCR) in 5-, 8-, and 10-week-old SCRs. A mild posterior and cortical opacity was observed in 5-week-old rats. Expressions of approximately 100 genes, including the major intrinsic protein of the lens fiber (Mip and Aquaporin 0), deoxyribonuclease II beta (Dnase2B), heat shock protein B1 (HspB1), and crystallin ? (?Cry) B, C, and F, were found to be significantly downregulated (0.07-0.5-fold) in rat LECs derived from cataract lenses compared to that in noncataractous lenses (control). Thus, our study was aimed at identifying the gene expression patterns during cataract formation in SCRs, which may be responsible for cataractogenesis in SCR. We proposed that cataracts in SCR are associated with reduced expression of these lens genes that have been reported to be related with lens fiber differentiation. Our findings may have wider implications in understanding the effect of cholesterol deficiency and the role of cholesterol-lowering therapeutics on cataractogenesis.