Genetic variants in the FOXO1 and ZNF469 genes are associated with keratoconus in Sweden: a case-control study.

BACKGROUND: Keratoconus (KC) is characterized by pathological thinning and bulging of the cornea that may lead to visual impairment. The etiology of sporadic KC remains enigmatic despite intensive research in recent decades. The purpose of this study was to examine the relationship between previously highlighted genetic variants associated with KC and sporadic KC in a Swedish cohort. METHODS: A total of 176 patients (age 16-70 years) with sporadic KC diagnosed by Scheimpflug-topography (Pentacam) were included. The control group (n = 418; age 70 years) was a subsample originating from the Gothenburg H70 Birth Cohort Studies of ageing. Extraction of DNA from blood samples was performed according to standard procedures, and genotyping was performed using competitive allele specific PCR (KASP) technology. A total of 11 single nucleotide polymorphisms (SNPs) were selected for analysis. RESULTS: Statistically significant associations (p = 0.005) were found between the SNPs rs2721051 and rs9938149 and sporadic KC. These results replicate earlier research that found associations between genetic variants in the FOXO1 and BANP-ZNF469 genes and sporadic KC in other populations. CONCLUSION: Genetic variations in the FOXO1 and BANP-ZNF469 genes may be involved in the pathogenesis of sporadic KC.

A Composite Risk Score for Capsule Complications Based on Data from the Swedish National Cataract Register: Relation to Surgery Volumes.

PURPOSE: To investigate case mix in relation to capsule complication, possible associations between case mix and operation volume, and change in case mix over time. DESIGN: Register-based study. PARTICIPANTS: Swedish patients who underwent cataract surgery between 2007 and 2016. METHODS: Demographics and data on ocular comorbidity, intraoperative difficulties, and capsule complications were registered from 2007 to 2016 and analyzed retrospectively in relation to coded data on individual surgeons' operation volume. Single factor analysis and logistic regression were performed, and a composite risk score was created. MAIN OUTCOME MEASURES: Risk of capsule complication, given as adjusted and composite odds ratio in relation to cataract surgery volume. RESULTS: Preoperative and intraoperative variables significantly associated with capsule complications were best-corrected visual acuity (BCVA) ≤0.1 (decimal, adjusted odds ratio [aOR], 1.82; P < 0.001); pseudoexfoliation (PEX) (aOR, 1.53; P < 0.001); sight-threatening ocular comorbidity other than age-related macular degeneration (AMD), diabetic retinopathy, glaucoma, or cornea guttata (aOR, 1.35; P = 0.006); use of Trypan blue (aOR, 1.76; P < 0.001); mechanical pupil dilation (aOR, 1.36; P = 0.024); and iris hooks at the rhexis margin (aOR, 6.99; P < 0.001). The composite risk score was 3.09 ± 6.40 (mean ± standard deviation) for patients with capsule complication and 1.28 ± 1.66 for uncomplicated procedures (P < 0.001). High-volume cataract surgeons (≥500 procedures yearly) had a significantly lower composite risk score (mean risk score ≤1.28; range, 1.01-2.02) compared with low- and medium-volume cataract surgeons (1.34 ± 0.56; range, 1.00-4.55 and 1.49 ± 0.58; range, 1.01-5.19), respectively. During the period 2007-2016, the proportion of patients aged >88 years, patients with BCVA ≤0.1, and patients with intraoperative difficulties decreased. CONCLUSIONS: Case mix, as calculated from a composite risk score based on preoperative and intraoperative parameters registered in the National Cataract Register (NCR), may contribute to the decrease in capsule complications from 2007 to 2016 and the lower complication rate observed in cases managed by high-volume cataract surgeons.

H2O2-induced cataract as a model of age-related cataract: Lessons learned from overexpressing the proteasome activator PA28αß in mouse eye lens.

Cataract, the world-leading cause of blindness, is formed when crystallin aggregates cloud the eye lens. We overexpressed PA28αß, a proteasome activator with properties protective against aggregation and oxidative stress, and examined whether they are less prone to develop cataract arisen from aging and/or hydrogen peroxide (H2O2) treatment. Another objective of this work was to compare the H2O2-induced cataracts of mouse lenses ex vivo to cataracts formed upon aging in mice. As part of an aging study of F2 hybrid C57BL/6NxBALB/c mice, ocular lenses of mature adult (7 months), middle-aged (15 months), and old (22 months of age) PA28αOE mice and their wildtype littermates (n = 22-44 lenses per group) were dissected and evaluated with regard to their cataractous state. In parallel, ocular lenses from 3 to 4 months old PA28αOE and wildtype C57BL/6 N littermates were treated with 100 µM H2O2 every 24 h for 7 days, with progression of cataract and physical appearance monitored daily. Lenses from both studies were also subjected to analysis of oxidative protein damage (carbonylation) and protein solubility. We found that overexpression of PA28αß had no effect on neither age-related nor H2O2-induced cataract and conclude that overexpression of PA28αß does not protect mice from developing cataract. The inefficiency of PA28αß against cataract could be due to its anti-aggregation activity being already excessively present in the eye lens, exerted by crystallins. Crystallins are likely also constituting the 20-25 kDa proteins that were the dominant carbonyl targets in the eye lens irrespective of cataractous state. Assessment of H2O2-induced cataract in relation to age-related cataract demonstrated that high molecular weight protein carbonylation correlates to cataract both in vivo and ex vivo, while reduced protein solubility is more pronounced in age-related cataract. Furthermore, this work highlights vast dissimilarities in the physical manifestations of cataract upon aging and H2O2 ex vivo treatment. Age-related cataract initiation can take various forms, as a vague general blurriness or as a barely visible demarcated opacity, while H2O2-induced cataractogenesis seems to follow a specific scheme. In mice, this scheme begins with relatively opaque peripheral areas emerging that clear up later on as the lenses start to display a hat-like appearance. This transformation takes place synchronous to swelling of the eye lens, and is likely a result of osmotic disturbances causing a phase separation between the viscous lens cortex and the more solid fibers of the lens nucleus.

Cataract Surgery Volumes and Complications per Surgeon and Clinical Unit: Data from the Swedish National Cataract Register 2007 to 2016.

PURPOSE: To investigate the change in proportion of high-volume cataract surgeons during the period 2007 to 2016 and determine the impact of operation volume per surgeon and clinical unit on the rate of capsule complications. DESIGN: Retrospective, register-based study. PARTICIPANTS: Patients undergoing and surgeons performing cataract surgery at Swedish ophthalmologic departments 2007-2016. METHODS: All cataract procedures performed during a 10-year period were analyzed, and the change in operation volume of individual surgeons over time was determined. The yearly incidence of capsule complications was correlated to the operation volume of individual surgeons and clinical units. MAIN OUTCOME MEASURES: The number of cataract procedures yearly per surgeon and clinical unit, proportion of capsule complications, and change over time in operation volume and complication rate. RESULTS: The proportion of high-volume (≥500 procedures yearly) and very high-volume (≥1000 procedures yearly) surgeons increased from 15.0% to 34.0% and 2.1% to 10.9%, respectively (P < 0.001 for both categories). The proportion of all cataract procedures performed by high-volume surgeons was 36.9% in 2007, increasing to 68.1% in 2016. The yearly incidence of capsule complications decreased with increasing number of procedures; from a mean of 2.15% (standard deviation [SD], 3.17) for low-volume surgeons (10-99 procedures/year) to 1.32% (1.28) for medium-volume (100-499 procedures/year) surgeons and 0.59% (0.49) for high-volume surgeons (P = 0.016). Preoperative best-corrected visual acuity was significantly better in eyes operated on by high-volume and very high-volume cataract surgeons; the median best-corrected visual acuity (BCVA) was 0.5 (decimal) compared with a BCVA of 0.4 for patients who had their surgery performed by low- or medium-volume surgeons (overall P < 0.001). No significant difference in rate of capsule complications was seen between clinical units with high or low operation volume (P = 0.804). The overall incidence of capsule complications decreased gradually from 1.5% in 2007 to 0.8% in 2016, and preoperative BCVA increased from 0.46±0.10 (logarithm of the minimum angle of resolution) to 0.40±0.05 (P = 0.030). CONCLUSIONS: There is a strong association of rate of capsule complications with operation volume of individual surgeons but not with operation volume of individual clinical units. The decreased rate of capsule complications seen between 2007 and 2016 may be explained in part by a dramatic increase in the proportion of high-volume cataract surgeons during the period.

The Gothenburg H70 Birth cohort study 2014-16: design, methods and study population.

To improve health care for older persons, we need to learn more about ageing, e.g. identify protective factors and early markers for diseases. The Gothenburg H70 Birth Cohort Studies (the H70 studies) are multidisciplinary epidemiological studies examining representative birth cohorts of older populations in Gothenburg, Sweden. So far, six birth cohorts of 70-year-olds have been examined over time, and examinations have been virtually identical between studies. This paper describes the study procedures for the baseline examination of the Birth cohort 1944, conducted in 2014-16. In this study, all men and women born 1944 on specific dates, and registered as residents in Gothenburg, were eligible for participation (n = 1839). A total of 1203 (response rate 72.2%; 559 men and 644 women; mean age 70.5 years) agreed to participate in the study. The study comprised sampling of blood and cerebrospinal fluid, psychiatric, cognitive, and physical health examinations, examinations of genetics and family history, use of medications, social factors, functional ability and disability, physical fitness and activity, body composition, lung function, audiological and ophthalmological examinations, diet, brain imaging, as well as a close informant interview, and qualitative studies. As in previous examinations, data collection serves as a basis for future longitudinal follow-up examinations. The research gained from the H70 studies has clinical relevance in relation to prevention, early diagnosis, clinical course, experience of illness, understanding pathogenesis and prognosis. Results will increase our understanding of ageing and inform service development, which may lead to enhanced quality of care for older persons.

PA28αß overexpression enhances learning and memory of female mice without inducing 20S proteasome activity.

BACKGROUND: The proteasome system plays an important role in synaptic plasticity. Induction and maintenance of long term potentiation is directly dependent on selective targeting of proteins for proteasomal degradation. The 20S proteasome activator PA28αß activates hydrolysis of small nonubiquitinated peptides and possesses protective functions upon oxidative stress and proteinopathy. The effect of PA28αß activity on behavior and memory function is, however, not known. We generated a mouse model that overexpresses PA28α (PA28αOE) to understand PA28αß function during healthy adult homeostasis via assessment of physiological and behavioral profiles, focusing on female mice. RESULTS: PA28α and PA28ß protein levels were markedly increased in all PA28αOE tissues analyzed. PA28αOE displayed reduced depressive-like behavior in the forced swim test and improved memory/learning function assessed by intersession habituation in activity box and shuttle box passive avoidance test, with no significant differences in anxiety or general locomotor activity. Nor were there any differences found when compared to WT for body composition or immuno-profile. The cognitive effects of PA28αOE were female specific, but could not be explained by alterations in estrogen serum levels or hippocampal regulation of estrogen receptor ß. Further, there were no differences in hippocampal protein expression of neuronal or synaptic markers between PA28αOE and WT. Biochemical analysis of hippocampal extracts demonstrated that PA28α overexpression did not increase PA28-20S peptidase activity or decrease K48-polyubiquitin levels. Instead, PA28αOE exhibited elevated efficiency in preventing aggregation in the hippocampus. CONCLUSIONS: This study reveals, for the first time, a connection between PA28αß and neuronal function. We found that PA28α overexpressing female mice displayed reduced depressive-like behavior and enhanced learning and memory. Since the positive effects of PA28α overexpression arose without an activation of 20S proteasome capacity, they are likely independent of PA28αß's role as a 20S proteasome activator and instead depend on a recognized chaperone-like function. These findings suggest that proteostasis in synaptic plasticity is more diverse than previously reported, and demonstrates a novel function of PA28αß in the brain.

Toric IOL implantation in a patient with keratoconus and previous penetrating keratoplasty: a case report and review of literature.

BACKGROUND: Cataract surgery in patients with keratoconus with or without previous penetrating keratoplasty (PKP) can be demanding due to difficulties in selecting the intraocular lens (IOL) and predicting the refractive outcome. We report a case of cataract surgery in a patient with keratoconus and previous PKP in one eye. CASE PRESENTATION: A 71-year-old man with bilateral cataract and advanced bilateral keratoconus and previous PKP in the left eye. Preoperatively, best corrected visual acuity (BCVA) was 20/150, with - 5.75 sph - 9.75 cyl 72°, in the right eye and 20/40, with - 0.25 sph - 5.0 cyl 50°, in the left eye. The patient was subjected to phacoemulsification with implantation of a spherical IOL in the right eye and a toric IOL in the left eye. BCVA postoperatively was 20/80 with + 1.25 sph - 3 cyl 65° in the right eye and 20/25 with - 0.5 sph - 3.25 cyl 80° in the left eye. CONCLUSIONS: Correction of post-PKP astigmatism and cataract with phacoemulsification and implantation of a toric IOL can be an effective and safe choice. Predicting the refractive outcome in cataract surgery is difficult in patients with advanced keratoconus even when using non-toric IOLs, and the surgeon should be aware of different sources of biometric errors and the possible consequences.

Oestradiol levels and superoxide dismutase activity in age-related cataract: a case-control study.

BACKGROUND: It has been suggested that the higher prevalence of cataract in women is caused by a withdrawal effect of oestrogen at menopause. In vitro studies have demonstrated protection of serum oestradiol (E2) against oxidative stress through upregulation of antioxidant enzymes, including superoxide dismutase (SOD). The purpose of the present study was to investigate E2 levels and SOD erythrocyte activity in patients with age-related cataract. METHODS: The studied subjects consisted of 103 patients with age-related cataract and 22 controls. Cataracts were classified as nuclear, cortical, or posterior subcapsular. Blood samples were collected and data on smoking, hormonal use, diabetes and age at menarche/menopause was obtained for all individuals. Serum oestradiol analyses were performed with radioimmunoassay (RIA) and SOD activity was measured in erythrocyte lysates. RESULTS: A negative correlation between age and E2 concentration was seen in a linear regression analysis. No correlation was seen between SOD activity and age or gender and no correlation between E2 levels and SOD activity was found using multiple linear regression. The mean level of E2 for all male subjects was 50.1 ± 16.3 pmol/L, significantly higher compared to 13.8 ± 11.8 pmol/L for postmenopausal women. CONCLUSION: The present study does not support a role for E2-induced effects on SOD in cataract formation. The findings of higher E2 levels in men than in postmenopausal women may suggest that decreased oestrogen at menopause is partially responsible for the gender-related difference in cataract prevalence. However, the latter can only be verified through prospective randomized trials using hormonal replacement therapy.

Five-year incidence of Nd:YAG laser capsulotomy and association with in vitro proliferation of lens epithelial cells from individual specimens: a case control study.

BACKGROUND: The aims of this study were to determine the 5-year incidence of posterior capsule opacification (PCO) requiring Nd:YAG laser capsulotomy in a representative mixed cohort of cataract patients, to determine risk factors for PCO and to investigate possible association with growth of human lens epithelial cells (HLEC) in vitro. METHODS: Pieces of the anterior lens capsule and adhering HLEC were obtained at cataract surgery and cultured individually. After one and two weeks respectively, cultured cells were stained with carboxy-fluorescein diacetate succinimidyl ester (CFDA SE), after which image processing software was used to determine the area of the confluent cell layer. The 5-year incidence of Nd:YAG laser capsulotomy in this cohort was determined through medical records and by mail or telephone interviews. For statistic analyses Mann-Whitney U-test, Fisher's exact test and binary logistic regression were used. RESULTS: Data on treatment/no treatment for PCO was obtained from 270 patients with a median follow-up time of 57 months (range 50-64 months). The three-year cumulative incidence of PCO was 5.2% and the cumulative 5-year incidence was 11.9%. Patients who had undergone Nd:YAG laser capsulotomy were significantly younger (median 71 years) than patients who did not receive treatment for PCO (median 75 years, p = 0.022). Logistic regression demonstrated that apart from younger age, follow-up time and type of intraocular lens (IOL) were associated with risk of PCO, with hydrophilic 1-piece IOLs conferring a higher risk than hydrophobic acrylic 1-piece or 3-piece IOLs (adjusted OR = 9.4, 95% CI 2.5-35.7, p = 0.001). Of the 270 patients from whom information could be retrieved regarding PCO treatment, in vitro cell culture could be established and quantified from 185 patients. No significant difference in cell growth in vitro was shown between patients subsequently requiring/not requiring Nd:YAG laser capsulotomy. CONCLUSIONS: The cumulative 5-year incidence of 11.9% is comparable or slightly higher than reported in other recent studies. The type of IOL was the most important risk factor for PCO in this study, whereas intrinsic proliferative capacity of the individual's lens epithelial cells seems to be less important for subsequent PCO development.

Optimal Performance of Selective Laser Trabeculoplasty: Results from the Swedish Optimal SLT Multicenter Randomized Controlled Trial.

PURPOSE: Selective laser trabeculoplasty (SLT) is a first-line treatment for glaucoma and ocular hypertension. However, due to insufficient comparative evidence in efficacy and safety, several SLT treatment protocols are currently used in practice. The objective of this trial was to compare the clinical outcomes of the 4 most significant SLT variants. DESIGN: Prospective, multicenter, masked, randomized controlled trial (RCT). PARTICIPANTS: Four hundred patients with glaucoma or ocular hypertension. The cohort consisted of both treatment-naive patients and patients undergoing glaucoma treatment, at different stages of disease. METHODS: Selective laser trabeculoplasty was performed with 50 ± 5 laser spots in 180 degrees or with 100 ± 10 spots in 360 degrees. The laser power was titrated to either just below the cavitation bubble level ("standard energy") or to a level producing cavitation bubbles at 50% to 75% of laser applications ("high energy"). Thus, 4 different treatment protocols were included - 180/standard, 180/high, 360/standard, and 360/high. The study adhered as close as possible to regular clinical management, but within a scientific framework. MAIN OUTCOME MEASURES: Reduction of intraocular pressure (IOP) 1 to 6 months after SLT. The proportion of patients achieving a 20% IOP reduction without any further intervention. Time to glaucoma treatment escalation in a Kaplan-Meier survival analysis. RESULTS: SLT performed with the 360/high protocol was shown to be superior regarding all primary endpoints. The IOP reduction 1 to 6 months after SLT was 5.4 mmHg in the 360/high group, compared to 3.4, 3.2, and 4.2 mmHg with the 180/standard, 180/high, and 360/standard protocols, respectively (P < 0.001). Furthermore, the success rate after 6 months was significantly higher -58.3%, compared with 30.2%, 29.3%, and 41.7% (P < 0.001). The median time to glaucoma treatment escalation was more than twice as long with 360/high SLT -1323 days, compared to 437 days, 549 days, and 620 days (P < 0.001). Although postoperative discomfort was more frequent with the 360/high protocol, symptoms were generally mild and transient. Adverse events were rare in all groups. CONCLUSIONS: The magnitude and longevity of SLT results increases substantially if SLT is performed according to the 360/high protocol, without compromising safety. Therefore, we recommend that 360/high SLT be considered as standard treatment. FINANCIAL DISCLOSURES: The authors have no proprietary or commercial interest in any materials discussed in this article.

Visual Improvement and Lowered Intraocular Pressure After Surgical Management of In-The-Bag Intraocular Lens Dislocation and Aphakia Correction; Retrospective Analysis of Scleral Suturing versus Retropupillary Fixated Iris-Claw Intraocular Lens During a 5-Year Period.

Purpose: We compare and evaluate the visual outcome and complication rate of two different techniques of surgical management of in-the-bag intraocular lens (IOL) dislocation or aphakia correction. In addition, we evaluate possible risk factors for IOL dislocation or aphakia. Patients and Methods: This retrospective case series reviewed medical records for all patients who had undergone surgery for IOL dislocation or aphakia during a 5-year period at a single ophthalmic center in Sweden. The two most common procedures, scleral suturing of dislocated in-the-bag IOL and retropupillary fixation of iris-claw IOL, were further analyzed. Main outcome measures were best-corrected visual acuity (BCVA), reoperations, and complications. Results: The study comprised 110 eyes, including scleral suturing procedures (n=35) and retropupillary iris-claw IOL (n=75). There was a significantly higher rate of dense cataract (p=0.030) and posterior capsular rupture (PCR), (p=0.016) among iris-claw cases at the primary cataract extraction with pseudoexfoliations in about two-thirds of patients in both groups. All eyes in the scleral suturing group had an IOL dislocation. In the iris-claw group, 23 eyes (30.7%) were aphakic following complicated cataract surgery with PCR. No intraoperative complications occurred in any eyes during the secondary IOL procedure. Both groups showed significant improvement in BCVA, yet there was no significant difference between groups in postoperative BCVA (p=0.263). However, the scleral suturing group experienced a significantly larger improvement in BCVA due to worse BCVA preoperatively (p=0.005). Intraocular pressure decreased significantly after both repositioning and exchange surgery (p=0.002 and 0.010 respectively), but improvement between groups was not significantly different (p=0.264). Conclusion: Both surgical methods resulted in significantly improved BCVA and lowering of IOP and can be considered safe with limited complications. The outcome was similar between groups. Pseudoexfoliation prevalence was high in both groups indicating that it may be a risk factor for either aphakia or late IOL dislocation.

Vision-related quality of life among 70-year-olds diagnosed with glaucoma.

PURPOSE: To evaluate the effect of glaucoma on vision-related quality of life (VRQoL), lifestyle, physical factors and socioeconomic status in a 70-year-old population in Gothenburg, Sweden. METHODS: Responses to questionnaires (N = 1182) between groups with and without self-reported glaucoma were analysed. Questionnaires included National Eye Institute Visual Functioning Questionnaire (NEI VFQ-25), Short-Form Health Survey (SF-36), physical activity, socioeconomics, alcohol and tobacco consumption. Balance test and body mass index were also included. About half of the participants were randomized to ophthalmic examination (N = 560), variables were analysed separately according to known and confirmed glaucoma, ocular hypertension and/or cases of previously unknown glaucoma. RESULTS: Both conventional and Rasch analysis of the NEI VFQ-25 showed that VRQoL was lower for individuals self-reporting glaucoma (p = 0.003/p = 0.024). Regarding general QoL, the participants did not differ apart from people self-reporting glaucoma reported worse general health (p = 0.01). Using logistic regression with lower VRQoL as the dependent variable glaucoma was not a significant predictor of poor VRQoL, odds ratio (OR) 1.83 (95% confidence interval (CI) 0.76-4.39, p = 0.18). Low household income was associated with lower VRQoL (OR 1.63, 95% CI 1.14-2.33, p = 0.01). Socioeconomics, physical activity and lifestyle factors were comparable between the groups (N = 915). Among participants who underwent ophthalmic examination no significant differences were found between glaucoma cases and non-glaucoma cases in relation to VRQoL (N = 560). CONCLUSIONS: Patients with self-reported glaucoma assessed a lower VRQoL but not lower general quality of life. Poorer household income was associated with worse VRQoL. General health was reported low in the glaucoma population but lifestyle or physical factors did not diverge.

The prevalence of glaucoma in a 70-year-old Swedish population in the city area of Gothenburg.

PURPOSE: To determine the prevalence of and risk factors for open-angle glaucoma in a population of 70-year-olds in Gothenburg, Sweden and to compare the visual function between the glaucoma population and the non-glaucoma population. METHODS: Of the entire cohort (n = 1203), 1182 participants responded a questionnaire on self-reported glaucoma and were tested for blood pressure (BP) and diabetes. In all, 560 participants underwent ophthalmic examination including best-corrected visual acuity (BCVA), intraocular pressure (IOP), central corneal thickness (CCT), contrast sensitivity (CS), perimetry and photos of the retina and lens. RESULTS: Glaucoma prevalence was 4.8% (95% confidence interval, 3.0%-6.6%), of which 56% was previously undiagnosed. The proportion of participants with diastolic BP >90 mmHg was higher in the non-glaucomatous group (8.3%) than the glaucoma group (0%), p < 0.001. A family history of glaucoma was present in a larger proportion of the glaucoma group (39%) than of the non-glaucomatous group (1.1%), p = 0.001. Mean IOP in individuals without glaucoma was 16 mmHg, versus 21 mmHg in participants with glaucoma detected at the examination. IOP was ≤21 mmHg in 67% among participants with previously unknown glaucoma. BCVA was lower in eyes with previously unknown glaucoma than in eyes without glaucoma (p = 0.017) but BCVA in the best eye did not differ. CCT and CS were similar in all cases. CONCLUSIONS: The prevalence of glaucoma was comparable to that reported previously. A family history of glaucoma and higher IOP were risk factors associated with glaucoma. BCVA in the best eye did not differ significantly between subjects with and without glaucoma.

A Novel Primary Porcine Retinal Pigment Epithelium Cell Model with Preserved Properties.

PURPOSE: To establish an ethical, reliable, and expandable retinal pigment epithelial (RPE) cell model with maintained RPE properties compatible with multifarious assays. METHODS: RPE cells from abattoir-obtained porcine eyes were cultured under various conditions. Morphology, RPE cell-specific protein markers (RPE-65, CRALBP), and the tight junction marker ZO-1 were analyzed by phase-contrast microscopy, immunocytochemistry, and western blot, and transepithelial electrical resistance (TEER) was determined to assess barrier function. RESULTS: The porcine RPE cells (pRPE) were best established using TrypLE Express, 10% fetal bovine serum (FBS) supplemented high-glucose media, and subculturing at semi-confluency. The pRPE cells maintained epithelioid morphology with ZO-1 positive tight junctions at the cell-to-cell borders, the ability to establish proper barrier function (TEERmax: 346/375 Ω⋅cm2 at passage I/passage VI), and expressed CRALBP and RPE-65 for several passages. The RPE characteristics decreased and disappeared with transdifferentiation. CONCLUSIONS: This work describes, for the first time, a pRPE cell model that exhibits preserved RPE properties for several passages on cell culture plastic plates. Though RPE characteristics were maintained for at least 6 passages, the reduced CRALBP and RPE-65 with passaging emphasize that lower passage cells are advantageous to utilize, and that morphology, barrier function, and ZO-1 localization cannot be solely employed as a quality measure of RPE identity. Pigs are phylogenetically similar to humans, including similar physiology, anatomy and immune system. Therefore, porcine RPE cells constitute a relevant model system for studying human eye diseases, such as AMD.

Ten-year trends of immediate sequential bilateral cataract surgery (ISBCS) as reflected in the Swedish National Cataract Register.

PURPOSE: To analyse trends of ISBCS reported to the Swedish National Cataract Register (NCR) over a 10-year period. METHODS: Since 2010 the NCR contains social security number of all individuals in the list of parameters reported to NCR after each cataract procedure. Bilateral surgeries were mapped out using social security numbers. When dates of both-eye surgeries are identical for an individual it is classified as an immediate sequential bilateral cataract surgery (ISBCS). This study includes all data reported during the period 1st of January 2010 to 31st of December 2019. During the study period 113 cataract surgery clinics affiliated to the NCR reported their data on consecutive cataract cases. RESULTS: For the whole period 54 194 ISBCS were reported. The total number of bilateral cataract extractions was 422 300. There was a significant trend of increasing ISBCS over time with linear regression (Beta = 1.75, p < 0.001). In ISBCS the occurrence of an ocular comorbidity decreased over time. The use of a capsular tension ring was significantly more common in ISBCS than in delayed sequential bilateral cataract surgery (DSBCS). All other measures taken during surgery were more common in DSBCS. The use of multifocal IOL was significantly more frequent in ISBCS compared to DSBCS (p < 0.001). CONCLUSIONS: The use of ISBCS has increased over the study period. The operated eyes have less risk factors than eyes going through a DSBCS, but both ocular comorbidities and surgical complications occur in ISBCS eyes.

[2.6 million cataract surgeries: 31 years with the Swedish National Cataract Register 1992-2022]. / 2,6 miljoner kataraktoperationer.

This review summarizes data collected by the Swedish National Cataract Register (NCR), which by the end of 2022 contained data on more than 2.6 million cataract surgeries between 1992-2022. During these 31 years, the cataract surgery rate (CSR) rose from 3 700 to 14 407. The coverage of NCR is very high, including 93% of all cataract procedures in Sweden during the last decade. A clear trend is that the procedure is performed in eyes with increasingly high visual acuity. The proportion of patients with Snellen 0.5 or worse in the first eye at surgery has decreased from 88% in 2007 to 69% in 2022. Patient Reported Outcome Measures (PROM) have been registered with the Catquest-9SF questionnaire since 2008, demonstrating stable favorable outcomes. Surgical complications have decreased; endophthalmitis has decreased from 0.10% to below 0.02%, and posterior capsule rupture from 2.8% to 0.6%.

The impact of topical NSAID treatment on selective laser trabeculoplasty efficacy.

PURPOSE: Selective laser trabeculoplasty (SLT) is a first-line intervention for glaucoma, with the aim to reduce the intraocular pressure (IOP). Topical non-steroidal anti-inflammatory drugs (NSAIDs) are sometimes prescribed after SLT. However, it has been proposed that such treatment may either increase or reduce SLT efficacy. The purpose of this study was to investigate this further. METHODS: The study was a retrospective chart review, including 192 eyes of 192 patients, half of which received a course of NSAID eyedrops after SLT. Absolute and relative IOP reduction 3-12 weeks after SLT was compared. Furthermore, subgroup analyses, a multiple linear regression analysis, and a Kaplan-Meier survival analysis regarding time to treatment escalation were performed. RESULTS: The mean absolute IOP reduction was 4.3 ± 3.4 mmHg in the NSAID group and 5.4 ± 4.1 mmHg in the control group (p = 0.049). Relative IOP reduction was 17.5% ± 13.0% and 21.8% ± 14.8% in the NSAID and control groups, respectively (p = 0.033). The same tendency of superior results in control eyes compared with NSAID eyes was seen in an extensive subgroup analysis. A multiple linear regression analysis confirmed NSAID treatment as a negative predictor of IOP reduction after adjustment for covariates (p = 0.023). Survival analysis showed a longer median time to treatment escalation in the control group, though not statistically significant. CONCLUSION: Topical NSAID treatment was not associated with an increased SLT efficacy. On the contrary, the present study is the first to demonstrate that SLT effectiveness may even be reduced by NSAIDs.