Madeleine Zetterberg

Late dislocation of in-the-bag and out-of-the bag intraocular lenses: Ocular and surgical characteristics and time to lens repositioning

PURPOSE: To characterize patients with late intraocular lens (IOL) dislocation to evaluate possible risk factors, determine the time between cataract surgery and IOL repositioning, describe the surgical management, and estimate the incidence. SETTING: Department of Ophthalmology, Sahlgrenska University Hospital, Mölndal, Sweden. DESIGN: Case series. METHODS: Medical records from the cataract surgery and IOL repositioning were reviewed. RESULTS: The study enrolled 84 eyes, 63 with in‐the‐bag IOL dislocation and 21 with out‐of‐the‐bag IOL dislocation. The prevalence of pseudoexfoliation (PXF) was 60% and of glaucoma, 36%. A high proportion of eyes with IOL dislocation (37%) had zonular dehiscence at cataract surgery. The median time from cataract surgery to IOL repositioning surgery was significantly shorter in eyes with out‐of‐the‐bag IOL dislocation (3.2 years) than in eyes with in‐the‐bag IOL dislocation (6.7 years) (P = .029). The interval was also significantly shorter in eyes with zonular dehiscence. Using data from the National Cataract Register, the calculated incidence of IOL repositioning surgery per pseudophakic individuals in western Sweden was 0.050%. CONCLUSIONS: The possible major predisposing factors for late IOL dislocation were PXF, glaucoma, and cataract surgery complicated by zonular dehiscence. Primary placement of the IOL in the ciliary sulcus was associated with earlier IOL dislocation. Intraocular lens repositioning surgery using a posterior or anterior approach was successful in many cases. Financial Disclosure: No author has a financial or proprietary interest in any material or method mentioned.

Nrf2-encoding NFE2L2 haplotypes influence disease progression but not risk in Alzheimer's disease and age-related cataract.

Alzheimers disease (AD) and age-related cataract, disorders characterized by protein aggregation causing late-onset disease, both involve oxidative stress. We hypothesize that common variants of NFE2L2 and KEAP1, the genes encoding the main regulators of the Nrf2 system, an important defence system against oxidative stress, may influence risk of AD and/or age-related cataract. This case-control study combines an AD material (725 cases and 845 controls), and a cataract material (489 cases and 182 controls). Genetic variation in NFE2L2 and KEAP1 was tagged by eight and three tag single nucleotide polymorphisms (SNPs), respectively. Single SNPs and haplotypes were analyzed for associations with disease risk, age parameters, MMSE and AD cerebrospinal fluid biomarkers. NFE2L2 and KEAP1 were not associated with risk of AD or cataract. However, one haplotype allele of NFE2L2 was associated with 2 years earlier age at AD onset (p(c)=0.013) and 4 years earlier age at surgery for posterior subcapsular cataract (p(c)=0.019). Another haplotype of NFE2L2 was associated with 4 years later age at surgery for cortical cataract (p(c)=0.009). Our findings do not support NFE2L2 or KEAP1 as susceptibility genes for AD or cataract. However, common variants of the NFE2L2 gene may affect disease progression, potentially altering clinically recognized disease onset.

Capsule complication during cataract surgery: Retinal detachment after cataract surgery with capsule complication: Swedish Capsule Rupture Study Group report 4.

PURPOSE: To study the incidence, characteristics, and results of retinal detachment (RD) after cataract surgery with a capsule complication. SETTING: Ten ophthalmic surgery departments in Sweden. METHODS: In this case‐control study, data on cataract surgery cases with a capsule complication (study group) or with no complication (control group) in 2003 were extracted from the Swedish National Cataract Register. Patients with RD during a 3‐year follow‐up were identified. RESULTS: The study group comprised 324 patients and the control group, 331 patients. Retinal detachment occurred in 13 study group patients, for a 3‐year incidence of 4.0%. In the control group, 1 patient (0.3%) had RD. Multivariate analysis showed an adjusted odds ratio (OR) of 14.8 for RD after capsule complication (95% confidence interval [CI], 1.9‐114; P = .01). Subgroup analysis of the study group using a binary logistic regression model showed that male sex (OR, 8.5; 95% CI, 1.7‐43.8; P = .001) and lens remnants in the vitreous (OR, 14.4; 95% CI 2.6‐78.8; P = .002) were additional risk factors. Axial myopia was significantly associated with an increased risk as a single factor but not as a multiple factor. In general, the final visual outcome for RD after a capsule complication was poor; 3 eyes had a visual acuity of 0.50 or better. Eight eyes (62%) had a final visual acuity worse than 0.10 and 6 eyes, 0.02 or worse. CONCLUSIONS: The risk for RD after cataract surgery increased significantly when a capsule complication occurred, leading to poor final visual acuity in most cases.

Proteasome activity in human lens nuclei and correlation with age, gender and severity of cataract.

Purpose. The aim of this study was to measure proteasome activity in human lens nuclei resulting from cataract surgery and in different regions of donor lenses. Methods. The chymotrypsin-like, the trypsin-like and the peptidylglutamyl-peptide hydrolysing activities of the proteasome were studied using synthetic flourogenic substrates. Results. Proteasome activity did not show any correlation with age of the patients or with gender. Increased opacification of the lens nucleus, as estimated prior to surgery using a 4-grade scale, was significantly correlated with decreased activity of all peptidase activities in the insoluble fraction. In the donor lenses, all peptidase activities were highest in the epithelium and decreased rapidly towards the nucleus. Conclusions. The present study demonstrates that proteasome activity is preserved in the nucleus of lenses from elderly individuals, although a decrease can be seen with cataract formation. This finding may be of importance for elucidating the mechanism behind the formation of nuclear cataract.

Age-related eye disease and gender

Worldwide, the prevalence of moderate to severe visual impairment and blindness is 285 millions, with 65% of visually impaired and 82% of all blind people being 50 years and older. Meta-analyses have shown that two out of three blind people are women, a gender discrepancy that holds true for both developed and developing countries. Cataract accounts for more than half of all blindness globally and gender inequity in access to cataract surgery is the major cause of the higher prevalence of blindness in women. In addition to gender differences in cataract surgical coverage, population-based studies on the prevalence of lens opacities indicate that women have a higher risk of developing cataract. Laboratory as well as epidemiologic studies suggest that estrogen may confer antioxidative protection against cataractogenesis, but the withdrawal effect of estrogen in menopause leads to increased risk of cataract in women. For the other major age-related eye diseases; glaucoma, age-related macular degeneration (AMD) and diabetic retinopathy, data are inconclusive. Due to anatomic factors, angle closure glaucoma is more common in women, whereas the dominating glaucoma type; primary open-angle glaucoma (POAG), is more prevalent in men. Diabetic retinopathy also has a male predominance and vascular/circulatory factors have been implied both in diabetic retinopathy and in POAG. For AMD, data on gender differences are conflicting although some studies indicate increased prevalence of drusen and neovascular AMD in women. To conclude, both biologic and socioeconomic factors must be considered when investigating causes of gender differences in the prevalence of age-related eye disease.

Potential Protective Effects of NSAIDs/ASA in Oxidatively Stressed Human Lens Epithelial Cells and Intact Mouse Lenses in Culture

Purpose: To study possible toxic effects of indomethacin, diclofenac, and celecoxib (NSAIDs) and acetylsalicylic acid (ASA) as well as potentially protective effects of these substances in oxidatively stressed human lens epithelial cells (HLEC) and in intact mouse lenses in culture. Methods: HLEC and mouse lenses were incubated with NSAIDs or ASA alone or in the presence of H2O2. To study apoptosis the cells were then either stained with Hoechst 33342 or assayed for caspase-3 activity. Mouse lenses were studied with respect to lens transparency. Results: Low concentrations of NSAIDs/ASA caused a significant protection against H2O2-induced apoptosis in HLEC whereas higher concentrations were toxic. Conclusion: The protective effects of NSAIDs/ASA against oxidative damage are confined to a relatively small therapeutic window.

Cytomegalovirus Retinitis in a Patient Who Received Ruxolitinib.

The Janus kinase 2 inhibitor ruxolitinib can produce defects in host defenses that may lead to opportunistic infections such as cytomegalovirus retinitis.

Methylenetetrahydrofolate Reductase Genetic Polymorphisms in Patients with Primary Open-Angle Glaucoma

Purpose: Hyperhomocysteinemia has been found in patients with primary open-angle glaucoma. The purpose of the present study was to determine if hyperhomocysteinemia-associated polymorphisms of the methylenetetrahydrofolate reductase gene (MTHFR) are overrepresented in primary open-angle glaucoma. Methods: Patients with primary open-angle glaucoma (n = 243) and controls (n = 187) were analyzed for the MTHFR 677 C > T and 1298 A > C polymorphisms using minisequencing technique. Results: No significant differences were observed in allele and genotype frequencies of the MTHFR 677C > T and 1298A > C polymorphisms between controls and the primary open-angle glaucoma group. Conclusions: If hyperhomocysteinemia is important in the pathogenesis of glaucoma, this study does not support a role for MTHFR polymorphisms in this context.

Surgical repositioning of intraocular lenses after late dislocation: Complications, effect on intraocular pressure, and visual outcomes

Purpose To study outcomes after surgery for late intraocular lens (IOL) dislocation and, more specifically, to evaluate different surgical techniques to find predictors of worse visual outcomes, describe postoperative complications, and analyze the effect on intraocular pressure (IOP). Setting Department of Ophthalmology, Sahlgrenska University Hospital, Mölndal, Sweden. Design Prospective observational cohort study. Methods Medical records from cataract surgery, IOL repositioning, and follow‐up examinations were reviewed. Results Ninety‐one eyes with in‐the‐bag (80) or out‐of‐the‐bag (11) late IOL dislocation were consecutively included. In 94% of eyes, the IOLs were repositioned using scleral sutures; 76% of cases were operated on with a posterior approach, including pars plana vitrectomy. The median follow‐up was 17 months. Pseudoexfoliation was detected in 57% of eyes. A significant decrease in IOP (mean 3.0 mm Hg) from preoperative values (P=.028) was seen in glaucoma patients. Thirteen eyes had additional surgical procedures. Three cases of retinal detachment occurred. Of the eyes, 59% obtained a Snellen corrected distance visual acuity (CDVA) of 0.5 or more at follow‐up; 23% of eyes had worse CDVA during the follow‐up than preoperatively. Conclusions Repositioning surgery for late IOL dislocation with a posterior pars plana approach using scleral suturing of the preexisting IOL appears to be a safe and effective method for restoring visual acuity. Postoperative complications were comparable to previous findings in this field. Patients with glaucoma may have improved IOP regulation. Financial Disclosure No author has a financial or proprietary interest in any material or method mentioned.

Gender and Cataract – The Role of Estrogen

Abstract There is evidence from epidemiologic data that cataract is more common in women than men. This is not solely due to a higher rate of cataract extraction in women, as is the case in the western world, but several population-based studies show that females have a higher prevalence of lens opacities, especially cortical. There is no firm evidence that lifestyle-related factors are the cause of this gender discrepancy. Focus has therefore been directed towards the role of estrogen in cataract formation. Although data on endogenous and exogenous estrogen involvement in cataractogenesis are conflicting, some studies have indicated that hormone therapy may decrease the risk of cataract and thus be protective. It has been hypothesized that the decrease in estrogen at menopause cause increased risk of cataract in women, i.e. not strictly the concentration of estrogen, but more the withdrawal effect. Estrogens are known to exert several anti-aging effects that may explain the longer lifespan in women, including metabolically beneficial effects, neuroprotection, preservation of telomeres and anti-oxidative properties. Since oxidative stress is considered important in cataractogenesis, studies have investigated the effects of estrogens on lens epithelial cells in culture or in animal models. Several investigators have found protection by physiological concentrations of 17β-estradiol against oxidative stress induced by H2O2 in cultured lens epithelial cells. Although both main types of estrogen receptors, ERα and ERβ, have been demonstrated in lens epithelium, most studies so far indicate that the estrogen-mediated protection in the lens is exerted through non-genomic, i.e. receptor-independent mechanisms, possibly through phosphorylation of extracellular signal-regulated kinase (ERK1/ERK2), a member of the mitogen-activated protein kinase (MAPK)-signaling pathway. Further studies are needed, both epidemiologic as to the role of hormone therapies, and laboratory studies regarding molecular estrogen-mediated mechanisms, in order to comprehend the role of estrogens on cataract formation.