Fenofibrate for diabetic retinopathy.

BACKGROUND: Diabetic retinopathy (DR) remains a major cause of sight loss worldwide, despite new therapies and improvements in the metabolic control of people living with diabetes. Therefore, DR creates a physical and psychological burden for people, and an economic burden for society. Preventing the development and progression of DR, or avoiding the occurrence of its sight-threatening complications is essential, and must be pursued to save sight. Fenofibrate may be a useful strategy to achieve this goal, by reversing diabetes' effects and reducing inflammation in the retina, as well as improving dyslipidaemia and hypertriglyceridaemia.  OBJECTIVES: To investigate the benefits and harms of fenofibrate for preventing the development and progression of diabetic retinopathy in people with type 1 (T1D) or type 2 diabetes (T2D), compared with placebo or observation. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, and three trials registers (February 2022). SELECTION CRITERIA: We included randomised controlled trials (RCTs) that included people with T1D or T2D, when these compared fenofibrate with placebo or with observation, and assessed the effect of fenofibrate on the development or progression of DR (or both). DATA COLLECTION AND ANALYSIS: We used standard Cochrane methods for data extraction and analysis. Our primary outcome was progression of DR, a composite outcome of 1) incidence of overt retinopathy for participants who did not have DR at baseline, or 2) advancing two or more steps on the Early Treatment Diabetic Retinopathy Study (ETDRS) severity scale for participants who had any DR at baseline (or both), based on the evaluation of stereoscopic or non-stereoscopic fundus photographs, during the follow-up period. Overt retinopathy was defined as the presence of any DR observed on stereoscopic or non-stereoscopic colour fundus photographs. Secondary outcomes included the incidence of overt retinopathy, reduction in visual acuity of participants with a reduction in visual acuity of 10 ETDRS letters or more, proliferative diabetic retinopathy, and diabetic macular oedema; mean vision-related quality of life, and serious adverse events of fenofibrate. We used GRADE to assess the certainty of evidence. MAIN RESULTS: We included two studies and their eye sub-studies (15,313 participants) in people with T2D. The studies were conducted in the US, Canada, Australia, Finland, and New Zealand; follow-up period was four to five years. One was funded by the government, the other by industry. Compared to placebo or observation, fenofibrate likely results in little to no difference in progression of DR (risk ratio (RR) 0.86; 95% confidence interval (CI) 0.60 to 1.25; 1 study, 1012 participants; moderate-certainty evidence) in a population with and without overt retinopathy at baseline. Those without overt retinopathy at baseline showed little or no progression (RR 1.00, 95% CI 0.68 to 1.47; 1 study, 804 participants); those with overt retinopathy at baseline found that their DR progressed slowly (RR 0.21, 95% CI 0.06 to 0.71; 1 study, 208 people; test for interaction P = 0.02). Compared to placebo or observation, fenofibrate likely resulted in little to no difference in either the incidence of overt retinopathy (RR 0.91; 95% CI 0.76 to 1.09; 2 studies, 1631 participants; moderate-certainty evidence); or the incidence of diabetic macular oedema (RR 0.39; 95% CI 0.12 to 1.24; 1 study, 1012 participants; moderate-certainty evidence). The use of fenofibrate increased severe adverse effects (RR 1.55; 95% CI 1.05 to 2.27; 2 studies, 15,313 participants; high-certainty evidence). The studies did not report on incidence of a reduction in visual acuity of 10 ETDRS letters or more, incidence of proliferative diabetic retinopathy, or mean vision-related quality of life. AUTHORS' CONCLUSIONS: Current, moderate-certainty evidence suggests that in a mixed group of people with and without overt retinopathy, who live with T2D, fenofibrate likely results in little to no difference in progression of diabetic retinopathy. However, in people with overt retinopathy who live with T2D, fenofibrate likely reduces the progression. Serious adverse events were rare, but the risk of their occurrence was increased by the use of fenofibrate. There is no evidence on the effect of fenofibrate in people with T1D. More studies, with larger sample sizes, and participants with T1D are needed. They should measure outcomes that are important to people with diabetes, e.g. change in vision, reduction in visual acuity of 10 ETDRS letters or more, developing proliferative diabetic retinopathy; and evaluating the requirement of other treatments, e.g. injections of anti-vascular endothelial growth factor therapies, steroids.

Scleral buckling versus pars plana vitrectomy in simple phakic macula-on retinal detachment: a propensity score-matched, registry-based study.

BACKGROUND/AIMS: To assess the anatomical and visual results of uncomplicated phakic macula-on retinal detachment (RD) in patients treated with pars plana vitrectomy (PPV) or scleral buckling (SB). METHODS: A retrospective cohort of patients aged <65 years and diagnosed with uncomplicated phakic macula-on primary RD, who were registered in the Japan-Retinal Detachment Registry, was compiled between February 2016 and March 2017. We performed propensity score matching using preoperative findings and surgeon-related factors as covariates to account for relevant confounders. The primary outcome was anatomical failures at 6 months postoperatively, classified as follows: level 1, an inoperable state; level 2, anatomical recovery with silicone oil tamponade; and level 3, need for additional surgery to repair the detachments. The secondary outcome was change in best-corrected visual acuity (BCVA). RESULTS: Of the 822 included patients, 552 underwent PPV and 270 underwent SB. After propensity score matching, 137 matched cases between the PPV and SB groups were analysed. The total proportion of surgical failures in the PPV group was higher than that in the SB group (risk difference, 0.10 (0.02 to 0.18), p=0.011, McNemar's test). Conversely, the change in BCVA was not significantly different between the two groups (logMAR units, -0.015 (-0.084 to 0.053), p=0.66, paired samples t-test). CONCLUSIONS: Although the indications for PPV are becoming broader, PPV may not be the optimal approach for repairing all types of RD. Therefore, careful consideration is needed when selecting the right surgical technique for treating uncomplicated phakic macula-on RD cases.

Differences in primary retinal detachment surgery conducted on holidays and workdays analyzed using the Japan Retinal Detachment Registry.

PURPOSE: To investigate the characteristics of retinal detachment (RD) and compare the outcomes of surgical interventions, such as scleral buckling (SB), pars plana vitrectomy (PPV), or PPV combined with SB, conducted on holidays and on workdays to determine the optimal surgical timing for primary RD treatment in clinical practice. STUDY DESIGN: Retrospective cohort study. METHODS: The cohort included 3178 patients with primary RD registered in the Japan Retinal Detachment Registry between February 2016 and March 2017. Surgery data were divided into holiday and workday groups. A descriptive analysis of primary RD characteristics was performed, and the outcomes for each surgical intervention were assessed. The primary outcome was anatomical failure at 6 months post-surgery classified as follows: level 1, inoperable state; level 2, anatomical recovery with silicone-oil use; and level 3, additional surgery required for RD repair. RESULTS: The holiday group comprised 108 and the workday, 3070 cases of primary RD. Compared with those in the workday group, surgery in the holiday group took longer (PPV, P < 0.0001; SB, P = 0.047) and was performed by less experienced surgeons (P = 0.014). However, there were no statistically significant differences in surgical failure 6 months post-surgery between the workday and holiday groups. CONCLUSION: Although surgery conducted on holidays and workdays was not significantly different in terms of outcome, some surgery should be postponed with proper preoperative interim measures to limit RD progress until it can be conducted on workdays by a well-prepared team.

Quantitative evaluations of vortex vein ampullae by adjusted 3D reverse projection model of ultra-widefield fundus images.

The purpose of this study was to determine the number and location of vortex vein ampullae (VVA) in normal eyes. This was an observational retrospective study. Montage images of one on-axis and two off-axis ultra-widefield images of 74 healthy eyes were enhanced, and reverse projected onto a 3D model eye. The number and distance between the optic disc to each VVA in the four sectors were compared. The significance of correlations between these values and age, sex, visual acuity, refractive error, and axial length was determined. The mean number of VVA was 8.10/eye with 1.84, 2.12, 2.19 and 1.95 in upper lateral, lower lateral, upper nasal, and lower nasal sectors, respectively. The mean number of VVA/eye was significantly greater in men at 8.43 than women at 7.76 (P = 0.025). The mean distance between the optic disc and VVA was 14.15 mm, and it was 14.04, 15.55, 13.29 and 13.66 mm in the upper lateral, lower lateral, upper nasal and lower nasal sectors, respectively (all P < 0.05). The number and location of VVA can be obtained non-invasively, and the number was significantly higher in men than women. This technique can be used to determine whether these values are altered in a retinochoroidal disease.

Japan-Retinal Detachment Registry Report I: preoperative findings in eyes with primary retinal detachment.

PURPOSE: To report the demographics and clinical characteristics of patients with a primary retinal detachment (RD). DESIGN: Prospective cohort study by a registry design. PARTICIPANTS: Patients with RD treated at vitreoretinal sub-specialty institutions in Japan from February 2016 to March 2017. METHODS: Descriptive statistics for the primary RD, and multivariable ordered logistic regression and multiple linear regression analyses were performed. RESULTS: 3178 eyes of 3178 cases were analyzed. The interval from onset to surgery was significantly shorter in patients in the 40-year age group than in other age groups except for the 50-year age group (P<0.05, Steel-Dwass test). The proportion of complex cases was significantly higher in the 10-year, 70-year, and 80+ year age groups than in the 40 and 50-year age groups (P<0.05, Steel-Dwass test). The size of RD was significantly associated with the male sex (odds ratio, 1.29; 95% confidence interval [CI], 1.07 to 1.56; P=0.0085) and the interval from onset to surgery (odds ratio, 1.03 95% CI, 1.01 to 1.04; P=0.0014). Low IOPs in eyes with RD were significantly associated with an older age (-0.24 mmHg/10 years, 95% CI, -0.32 to -0.16], P<0.0001) and larger RD area (-0.91 mmHg/quadrant, 95% CI, [-1.06 to -0.76], P <0.0001). CONCLUSION: Profile and clinical characteristics of patients with a primary RD were not exactly the same as previous reports. A preoperative low IOP was associated with several ocular factors while the area of RD was associated not only with ocular but with social factors as well.

Current status of late and recurrent intraocular lens dislocation: analysis of real-world data in Japan.

PURPOSE: To describe relevant patient demographic characteristics and investigate the influence of known risk factors for late intraocular lens (IOL) dislocation. To explore the associations between these risk factors and the incidence of recurrent IOL dislocation. STUDY DESIGN: Retrospective cohort study. METHODS: This study was performed using Nationwide Diagnostic Procedure Combination data in Japan from April 1, 2008 through July 31, 2016. Descriptive statistics for late and recurrent IOL dislocation, incidence rates, and risk factors for recurrent IOL dislocation were analyzed using a Cox proportional hazard model. RESULTS: We identified 678 patients with late IOL dislocation. Most were men (72%, 488/678), and the men were younger than their women counterparts (mean age 65.2 years vs. 74.5 years). The incidence rate of recurrent IOL dislocation was 5.1 per 100 person-years. All 20 cases of recurrent IOL dislocation were observed within the year following surgery. There were no significant associations between potential risk factors and recurrent IOL dislocation (adjusted hazard ratio [HR] 1.53, 95% confidence interval [CI] 0.55-4.26 for diabetes mellitus; adjusted HR 0.77, 95%CI 0.09-6.40 for atopic dermatitis); no recurrences occurred in patients with pseudoexfoliation syndrome, retinitis pigmentosa, or connective tissue disease. CONCLUSIONS: Late IOL dislocation occurs more frequently in men. We found that recurrent IOL dislocation was rare during long-term follow-up and there were no significant associations between the potential risk factors and recurrent IOL dislocation. Further studies are needed to clarify the sex-related differences involved in IOL dislocation.

Quantitative analysis of the effects of extracellular matrix proteins on membrane dynamics associated with corneal epithelial cell motility.

PURPOSE: Interaction of corneal epithelial cells with components of the basement membrane regulates cell morphology, adhesion, and migration. The authors examined the effects of basement membrane components on the behavior of human corneal epithelial (HCE) cells, including movement of the cell membrane in relation to the direction of cell migration. METHODS: HCE cells were plated on fibronectin, laminin, collagen types I and IV, and bovine serum albumin (BSA). Cell adhesion was evaluated by staining with crystal violet. Cell movement was monitored by time-lapse microscopy, and an image processing program was developed for quantitative analysis of movement of the cell membrane in relation to the direction of cell migration. Actin cytoskeleton, focal adhesions, and the K+ channel Kv2.1 were detected by fluorescence microscopy. RESULTS: Laminin, fibronectin, and collagen types I and IV each promoted cell adhesion compared with that apparent with BSA. Fibronectin and collagen types I and IV, but not laminin, increased cell motility. Laminin had no effect on membrane movement compared with that observed in the presence of BSA. Collagen types I and IV each increased membrane movement but in a manner independent of the direction of cell migration. Fibronectin induced membrane movement in the direction of cell migration. Fibronectin induced the formation of thick bundles of F-actin and focal adhesions at the cell periphery and the localization of Kv2.1 at the leading edge of the cell, whereas laminin and collagen types I and IV elicited the formation of thinner bundles of F-actin and smaller focal adhesions. CONCLUSIONS: Fibronectin may modulate the directional migration of corneal epithelial cells.