A New Small-Aperture Device Implanted on Top of the Intraocular Lens: Safety, Feasibility, and First Clinical Results.

PURPOSE: To investigate the feasibility and safety of a new small-aperture device, which is implanted on top of the intraocular lens. METHODS: Regular cataract surgery was performed in both eyes in 7 patients. In the non-dominant eye, a small-aperture device (VisionXtender; Morcher) was additionally implanted into the capsular bag at the end of the surgery. The mask had an inner diameter of 1.4 mm. Feasibility and safety were investigated 3 months and 2 years after surgery. RESULTS: In all cases, the device was successfully positioned in the capsular bag without any intraoperative complications. No inflammation was observed at the 3-month follow-up visit. All patients achieved binocular uncorrected distance visual acuity of 0 logarithm of the minimum angle of resolution (log-MAR) or better. Additionally, distance-corrected intermediate visual acuity of 0.1 logMAR or better was measured in the non-dominant eye. Two years postoperatively, Nd:YAG capsulotomy was performed in three patients in both eyes. CONCLUSIONS: This clinical feasibility trial demonstrates that the use of the new small-aperture device is both easy and safe. No intraoperative or postoperative complications were reported. All patients attained satisfactory distance, intermediate, and near visual acuity. The device shows significant potential when used in combination with different intraocular lenses (eg, toric). In the future, different opening shapes seem to be possible. [J Refract Surg. 2024;40(9):e662-e666.].

A cardiac-rehab behaviour intervention to reduce sedentary time in coronary artery disease patients: the SIT LESS randomized controlled trial.

BACKGROUND: High sedentary times (ST) is highly prevalent in patients with coronary artery disease (CAD), highlighting the need for behavioural change interventions that effectively reduce ST. We examined the immediate and medium-term effect of the SIT LESS intervention on changes in ST among CAD patients enrolled in cardiac rehabilitation (CR). METHODS: CAD patients participating in CR at 2 regional hospitals were included in this randomized controlled trial (1:1, stratified for gender and hospital). The control group received CR, whereas SIT LESS participants additionally received a 12-week hybrid behaviour change intervention. The primary outcome was the change in accelerometer-derived ST from pre-CR to post-CR and 3 months post-CR. Secondary outcomes included changes in ST and physical activity characteristics, subjective outcomes, and cardiovascular risk factors. A baseline constrained linear mixed-model was used. RESULTS: Participants (23% female; SIT LESS: n = 108, control: n = 104) were 63 ± 10 years. Greater ST reductions were found for SIT LESS compared to control post-CR (-1.7 (95% confidence interval (CI): -2.0; -1.4) versus - 1.1 (95% CI: -1.4; -0.8) h/day, pinteraction=0.009), but not at 3 months post-CR (pinteraction=0.61). Besides, larger light-intensity physical activity (LIPA) increases were found for SIT LESS compared to control post-CR (+ 1.4 (95% CI: +1.2; +1.6) versus + 1.0 (95% CI: +0.8; +1.3) h/day, pinteraction=0.020). Changes in other secondary outcomes did not differ among groups. CONCLUSION: SIT LESS transiently reduced ST and increased LIPA, but group differences were no longer significant 3 months post-CR. These findings highlight the challenge to induce sustainable behaviour changes in CAD patients without any continued support. TRIAL REGISTRATION: Netherlands Trial Register: NL9263. Registration Date: 24 February 2021.

Impact of Hypertension on the Dose-Response Association Between Physical Activity and Stroke: A Cohort Study.

BACKGROUND: Regular physical activity is associated with a reduced stroke risk. However, this relationship might be attenuated in the presence of hypertension and antihypertensive medication use. We examined the dose-response relationship between physical activity and stroke in normotensive and hypertensive individuals. METHODS: A Dutch population-based cohort including 139 930 individuals (41% men; mean age, 44±13) was performed (median follow-up, 6.75 years). Participants were stratified at baseline as hypertensive (44%) or normotensive (56%) and categorized into quartiles of the lowest (Q1) to the highest (Q4) moderate-to-vigorous, self-reported physical activity. The primary outcome was incident stroke (fatal and nonfatal). Cox regression estimated hazard ratios and 95% CIs. The main analyses were stratified on baseline blood pressure and adjusted for confounders. Hypertensives were stratified into medicated (21%) or non-medicated (79%). RESULTS: Compared with Q1, adjusted hazard ratios were 0.87 (0.69-1.10; P=0.23), 0.75 (0.59-0.95; P=0.02), and 0.94 (0.74-1.20; P=0.64) for Q2 to Q4, respectively in the total population. Hazard ratios for normotensives were 0.79 (0.50-1.25; P=0.32), 0.75 (0.48-1.18; P=0.22), 0.97 (0.62-1.51; P=0.90) for Q2 to Q4, respectively. In hypertensives, hazard ratios were 0.89 (0.68-1.17; P=0.41), 0.74 (0.56-0.98; P=0.03), 0.92 (0.69-1.23; P=0.56) for Q2 to Q4, respectively. There was no significant interaction between hypertension status for the relation between physical activity and stroke risk. The stratified analysis revealed a smaller benefit of moderate-to-vigorous physical activity in medicated hypertensives compared with nonmedicated hypertensives, but no significant interaction effect was found. CONCLUSIONS: Regular moderate-to-vigorous physical activity is beneficial for stroke risk reduction (Q3 compared with Q1), which is not affected by hypertension. Antihypertensive medication may be associated with a smaller benefit of moderate-to-vigorous physical activity on the risk of stroke, but further research is warranted.

Retinal debris triggers cytotoxic damage in cocultivated primary porcine RPE cells.

Introduction: One of the most common causes of vision loss in the elderly population worldwide is age-related macular degeneration (AMD). Subsequently, the number of people affected by AMD is estimated to reach approximately 288 million by the year 2040. The aim of this study was to develop an ex vivo model that simulates various aspects of the complex AMD pathogenesis. Methods: For this purpose, primary porcine retinal pigment epithelial cells (ppRPE) were isolated and cultured. One group was exposed to medium containing sodium iodate (NaIO3) to induce degeneration. The others were exposed to different supplemented media, such as bovine serum albumin (BSA), homogenized porcine retinas (HPR), or rod outer segments (ROOS) for eight days to promote retinal deposits. Then, these ppRPE cells were cocultured with porcine neuroretina explants for another eight days. To assess the viability of ppRPE cells, live/dead assay was performed at the end of the study. The positive RPE65 and ZO1 area was evaluated by immunocytochemistry and the expression of RLBP1, RPE65, and TJP1 was analyzed by RT-qPCR. Additionally, drusen (APOE), inflammation (ITGAM, IL6, IL8, NLRP3, TNF), oxidative stress (NFE2L2, SOD1, SOD2), and hypoxia (HIF1A) markers were investigated. The concentration of the inflammatory cytokines IL-6 and IL-8 was determined in medium supernatants from day 16 and 24 via ELISA. Results: Live/dead assay suggests that especially exposure to NaIO3 and HPR induced damage to ppRPE cells, leading in a significant ppRPE cell loss. All supplemented media resulted in decreased RPE-characteristic markers (RPE65; ZO-1) and gene expression like RLBP1 and RPE65 in the cultured ppRPE cells. Besides, some inflammatory, oxidative as well as hypoxic stress markers were altered in ppRPE cells cultivated with NaIO3. The application of HPR induced an enhanced APOE expression. Pre-exposure of the ppRPE cells led to a diminished number of cones in all supplemented media groups compared to controls. Discussion: Overall, this novel coculture model represents an interesting initial approach to incorporating deposits into coculture to mimic AMD pathogenesis. Nevertheless, the effects of the media used need to be investigated in further studies.

Left ventricular strain-volume loops in bicuspid aortic valve disease: new insights in cardiomechanics.

Aims: By combining temporal changes in left ventricular (LV) global longitudinal strain (GLS) with LV volume, LV strain-volume loops can assess cardiac function across the cardiac cycle. This study compared LV strain-volume loops between bicuspid aortic valve (BAV) patients and controls, and investigated the loop's prognostic value for clinical events. Methods and results: From a prospective cohort of congenital heart disease patients, BAV patients were selected and compared with healthy volunteers, who were matched for age and sex at group level. GLS analysis from apical views was used to construct strain-volume loops. Associations with clinical events, i.e. a composite of all-cause mortality, heart failure, arrhythmias, and aortic valve replacement, were assessed by Cox regression. A total of 113 BAV patients were included (median age 32 years, 40% female). BAV patients demonstrated lower Sslope (0.21%/mL, [Q1-Q3: 0.17-0.28] vs. 0.27%/mL [0.24-0.34], P < 0.001) and ESslope (0.19%/mL [0.12-0.25] vs. 0.29%/mL [0.21-0.43], P < 0.001) compared with controls, but also greater uncoupling during early (0.48 ± 1.29 vs. 0.05 ± 1.21, P = 0.04) and late diastole (0.66 ± 1.02 vs. -0.07 ± 1.07, P < 0.001). Median follow-up duration was 9.9 [9.3-10.4] years. Peak aortic jet velocity (HR 1.22, P = 0.03), enlarged left atrium (HR 3.16, P = 0.003), E/e' ratio (HR 1.17, P = 0.002), GLS (HR 1.16, P = 0.008), and ESslope (HR 0.66, P = 0.04) were associated with the occurrence of clinical events. Conclusion: Greater uncoupling and lower systolic and diastolic slopes were observed in BAV patients compared with healthy controls, suggesting presence of altered LV cardiomechanics. Moreover, lower ESslope was associated with clinical events, highlighting the strain-volume loop's potential as prognostic marker.

Detecting Keratoconus in Adolescents with Anterior Segment Optical Coherence Tomography.

Purpose: Assessing the applicability of an algorithm developed for keratoconus detection in adolescents. This algorithm relies on optical coherence tomography (OCT) and incorporates features related to corneal pachymetric and epithelial thickness alterations. Methods: We retrospectively reviewed charts of patients under the age of 18 and divided them into four groups according to the Belin-Ambrosio display (Pentacam): normal, manifest, and subclinical keratoconus, as well as very asymmetric eye with normal topography and tomography (VAE-NTT). Corneal and epithelial thickness maps (Cirrus 5000 HD-OCT, Carl Zeiss Meditec, Germany) were evaluated by a human grader. In the first step, if at least one of four parameters (pachymetry minimum (pachy min), pachy minimum-median (min-med), pachy superonasal-inferotemporal (SN-IT), or epithelial (epi SN-IT)) exceeded its cut-off value, the eye was considered as suspect. In the second step, the combined presence of coincident thinning of total cornea and epithelium as well as concentric epithelial thinning lead to the diagnosis of keratoconus. Receiver operating characteristic (ROC) curves were generated to determine area under the curve (AUC), sensitivity, and specificity for the parameters. Results: The study involved 19 pediatric patients diagnosed with keratoconus, comprising 29 manifest keratoconic eyes, 3 eyes with subclinical keratoconus, and 5 VAE-NTT eyes. In addition, 22 eyes from 11 normal adolescents were included in the analysis. The AUC values of parameters in step 1 were 0.889 for pachy min, 0.997 for pachy min-med, 0.893 for pachy SN-IT, and 0.998 for epi SN-IT. When both steps were performed, this algorithm captured all manifest and subclinical pediatric keratoconic eyes. When all eyes of the keratoconus patients were combined, step 1 had 97.3% sensitivity and step 2 had 100% specificity. Conclusion: Using this OCT-based approach in adolescents yielded a high level of agreement with the current gold standard, tomography. Using them together, potentially also with other examinations may improve the diagnostic accuracy of KC in the pediatric population. Integration of this approach into the software of the device to facilitate automated evaluations is desired.

Risk Factors for Re-treatment After Keratorefractive Lenticule Extraction (KLEx) for Myopia and Myopic Astigmatism.

PURPOSE: To identify potential risk factors that increase the likelihood of re-treatment following keratorefractive lenticule extraction (KLEx) for myopia and myopic astigmatism. METHODS: This was a retrospective study of patients with myopia and myopic astigmatism who underwent KLEx using the VisuMax 500 laser (Carl Zeiss Meditec) between April 2015 and December 2020. Patients were assigned to one of two groups: the control group and the re-treatment group (if they had additional refractive surgery within 2 years of the primary treatment). The effect of different preoperative, intraoperative, and postoperative parameters on the re-treatment rate was analyzed. RESULTS: Overall 1,822 eyes of 938 patients were analyzed. In total, 2.96% of eyes (n = 54) underwent re-treatment. The re-treated patients were more likely to be women and have high myopia, high astigmatism, steep corneas, higher ocular residual astigmatism, and residual myopic and/or astigmatic refractive error. In contrast, no significant correlation was found between re-treatment rate and age, chord µ, type of astigmatism, and corneal thickness. CONCLUSIONS: Factors associated with higher rates of retreatment after KLEx included female gender, manifest refractive high myopia (> -5.00 diopters [D]), astigmatism (> 2.00 D), spherical equivalent (> 6.00 D), ocular residual astigmatism, steeper corneas, and postoperative residual myopic and astigmatic refractive errors. This study may help to preoperatively detect patients at risk for re-treatment, improve preoperative patient counseling, and optimize patient selection to reduce future re-treatment rates. [J Refract Surg. 2024;40(6):e362-e370.].

[Cell loss in retinal ischemia is associated with increased necroptosis]. / Zellverlust bei retinaler Ischämie ist assoziiert mit vermehrter Nekroptose.

BACKGROUND: Retinal ischemia plays a central pathophysiological role in numerous eye diseases, such as glaucoma. In addition to apoptosis, autophagy, necroptosis and ferroptosis are among the cell death mechanisms of ischemia; however, their role is not clearly understood and controversially discussed. OBJECTIVE: The aim of this study is to gain an improved understanding of the role of alternative cell death mechanisms such as autophagy and necroptosis after retinal ischemia. Based on this, future autophagy-based or necroptosis-based therapeutic approaches could be developed. MATERIAL AND METHODS: Retinal ischemia reperfusion was induced in one eye of 6 to 8­week-old rats by temporarily increasing the intraocular pressure to 140 mm Hg (60 min), followed by reperfusion. The untreated contralateral eye served as a control. Retinas after ischemia and control retinas were examined 7 days after ischemia immunohistochemically with markers for retinal ganglion cells (RGC), astrocytes (GFAP) as well as an autophagy (LAMP1) and a necroptosis marker (RIPK3) (n = 6/group). RESULTS: Ischemia reperfusion resulted in both significant RGC loss (p ≤ 0.001) and a significant increase of astrocyte area (p = 0.026) after 7 days. Interestingly, the number of autophagic LAMP1 positive cells was unchanged 7 days after ischemia (p = 0.272), whereas the number of necroptotic RIPK3 positive cells was significantly increased (p ≤ 0.001). CONCLUSION: Necroptotic processes appear to be activated 7 days after ischemia reperfusion, contributing to retinal cell death and activation of astrocytes. Late autophagic processes are not activated 7 days after ischemia. Necroptosis-associated parameters could therefore be targeted as an early therapeutic approach after ischemia in the future.