A view from the clinic – Perspectives from Dutch patients and professionals on high myopia care

Purpose: To understand and compare perspectives of patients and professionals on current ophthalmologic care for high myopia, and to identify challenges and future opportunities. Methods: Self-reported data were collected through two online questionnaires. Patient perspective was obtained from highly myopic members of a patient organisation based in the Netherlands using a 17-item questionnaire consisting of open and multiple-choice questions regarding personal experience with myopia care. The ophthalmologist perspective was obtained from practising Dutch ophthalmologists with a 12-item questionnaire of multiple-choice questions on work-related demographics, myopia care in daily practice and need for improvement. The response rate for patients was 27% (n = 136/500) and for ophthalmologists, 24% (n = 169/716). Results: Patients were highly concerned about personal progressive loss of vision (69%) and feared their psychological well-being (82%) in case this would happen. The quality of performance of care provided by ophthalmologists was rated as excellent or satisfactory by 64% of the patients. These ratings for multidisciplinary care and insurance reimbursement were as low as 28% and 18% respectively. The mean concern among ophthalmologists about the rise in high myopia was 6.9 (SEM 0.1) on a 10-point scale. Sixty-nine per cent of the ophthalmologists reported that asymptomatic myopic patients should not be examined regularly at outpatient clinics. Ophthalmologists urged the development of clinical guidelines (74%), but did report (95%) that they informed patients about risk factors and complications. This contrasted with the view of patients, of whom 42% were discontent with information provided by ophthalmologists. Conclusions: These questionnaires demonstrated that the current clinical care delivered to highly myopic patients is in need of improvement. The expected higher demand for myopia care in the near future requires preferred practice patterns, professionals specifically trained to manage myopic pathology, accurate and comprehensive information exchange and collaboration of in- and out-of-hospital professionals across the full eye care chain.</p

Descemet Membrane Endothelial Keratoplasty versus Ultrathin Descemet Stripping Automated Endothelial Keratoplasty A Multicenter Randomized Controlled Clinical Trial

Purpose: To compare best spectacle-corrected visual acuity (BSCVA), endothelial cell density (ECD), refractive astigmatism, and complications after Descemet membrane endothelial keratoplasty (DMEK) and ultrathin Descemet stripping automated endothelial keratoplasty (UT-DSAEK). Design: Prospective, multicenter randomized controlled trial. Participants: Fifty-four pseudophakic eyes of 54 patients with corneal endothelial dysfunction resulting from Fuchs endothelial corneal dystrophy were enrolled in 6 corneal centers in The Netherlands. Methods: Participants were allocated to DMEK (n = 29) or UT-DSAEK (n = 25) using minimization randomization based on preoperative BSCVA, recipient central corneal thickness, gender, age, and institution. Donor corneas were prestripped and precut for DMEK and UT-DSAEK, respectively. Six corneal surgeons participated in this study. Main Outcome Measures: The primary outcome measure was BSCVA at 12 months after surgery. Results: Central graft thickness of UT-DSAEK lamellae measured 101 mu m (95% confidence interval [CI], 90-112 mu m). Best spectacle-corrected visual acuity did not differ significantly between DMEK and UT-DSAEK groups at 3 months (0.15 logarithm of the minimum angle of resolution [logMAR] [95% CI 0.08-0.22 logMAR] vs. 0.22 logMAR [95% CI 0.16-0.27 logMAR]; P = 0.15), 6 months (0.11 logMAR [95% CI 0.05-0.17 logMAR] vs. 0.16 logMAR [95% CI 0.12-0.21 logMAR]; P = 0.20), and 12 months (0.08 logMAR [95% CI 0.03-0.14 logMAR] vs. 0.15 logMAR [95% CI 0.10-0.19 logMAR]; P = 0.06). Twelve months after surgery, the percentage of eyes reaching 20/25 Snellen BSCVA was higher in DMEK compared with UT-DSAEK (66% vs. 33%; P = 0.02). Endothelial cell density did not differ significantly 12 months after DMEK and UT-DSAEK (1870 cells/mm 2 [95% CI 1670-2069 cells/mm(2)] vs. 1612 cells/mm(2) [95% CI 1326-1898 cells/mm(2)]; P = 0.12). Both techniques induced a mild hyperopic shift (12 months: +0.22 diopter [D; 95% CI -0.23 to 0.68 D] for DMEK vs. +0.58 D [95% CI 0.13-1.03 D] for UT-DSAEK; P = 0.34). Conclusions: Descemet membrane endothelial keratoplasty and UT-DSAEK did not differ significantly in mean BSCVA, but the percentage of eyes achieving 20/25 Snellen vision was significantly higher with DMEK. Endothelial cell loss did not differ significantly between the treatment groups, and both techniques induced a minimal hyperopic shift. (C) 2020 by the American Academy of Ophthalmolog

Trial-based cost-effectiveness analysis of ultrathin Descemet stripping automated endothelial keratoplasty (UT-DSAEK) versus DSAEK

Purpose: To evaluate the cost-effectiveness of ultrathin Descemet stripping automated endothelial keratoplasty (UT-DSAEK) versus standard DSAEK. Methods: A cost-effectiveness analysis using data from a multicentre randomized clinical trial was performed. The time horizon was 12 months postoperatively. Sixty-four eyes of 64 patients with Fuchs’ endothelial dystrophy were included and randomized to UT-DSAEK (n = 33) or DSAEK (n = 31). Relevant resources from healthcare and societal perspectives were included in the cost analysis. Quality-adjusted life years (QALYs) were determined using the Health Utilities Index Mark 3 questionnaire. The main outcome was the incremental cost-effectiveness ratio (ICER; incremental societal costs per QALY). Results: Societal costs were €9431 (US$11 586) for UT-DSAEK and €9110 (US$11 192) for DSAEK. Quality-adjusted life years (QALYs) were 0.74 in both groups. The ICER indicated inferiority of UT-DSAEK. The cost-effectiveness probability ranged from 37% to 42%, assuming the maximum acceptable ICER ranged from €2500–€80 000 (US$3071–US$98 280) per QALY. Additional analyses were performed omitting one UT-DSAEK patient who required a regraft [ICER €9057 (US$11 127) per QALY, cost-effectiveness probability: 44–62$29 271) per QALY, cost-effectiveness probability: 36–59%]. Furthermore, the ICER was €2101 (US$2581) per patient with clinical improvement in best spectacle-corrected visual acuity (≥0.2 logMAR) and €3274 (US$4022) per patient with clinical improvement in National Eye Institute Visual Functioning Questionnaire-25 composite score (≥10 points). Conclusion: The base case analysis favoured DSAEK, since costs of UT-DSAEK were higher while QALYs were comparable. However, additional analyses revealed no preference for UT-DSAEK or DSAEK. Further cost-effectiveness studies are required to reduce uncertainty

Quality of vision and vision-related quality of life after Descemet membrane endothelial keratoplasty:a randomized clinical trial

PURPOSE: To compare quality of vision and vision‐related quality of life (QOL) in patients undergoing Descemet membrane endothelial keratoplasty (DMEK) or ultrathin Descemet stripping automated endothelial keratoplasty (DSAEK). METHODS: Fifty‐four eyes of 54 patients with Fuchs' dystrophy from six corneal clinics in the Netherlands were randomized to DMEK or ultrathin DSAEK and examined preoperatively, and 3, 6 and 12 months postoperatively. Main outcome measures were corneal higher‐order aberrations (HOAs), contrast sensitivity, straylight and vision‐related QOL. RESULTS: Posterior corneal HOAs decreased after DMEK and increased after ultrathin DSAEK (p ≤ 0.001) 3 months after surgery and correlated positively with best spectacle‐corrected visual acuity (12 months: r = 0.29, p = 0.04). Anterior and total corneal HOAs did not differ significantly between both techniques at any time point. Contrast sensitivity was better (p = 0.01), and straylight was lower (p = 0.01) 3 months after DMEK compared with ultrathin DSAEK; 95% confidence interval [CI] of log(cs) 1.10–1.35 versus 95% CI: 0.84 to 1.12, and 95% CI: log(s) 1.18 to 1.43 versus 95% CI: 1.41 to 1.66, respectively. Both were comparable at later time points. Vision‐related QOL (scale 0–100) did not differ significantly between both groups at any time point and improved significantly at 3 months (β = 12 [95% CI: 7 to 16]; p < 0.001), and subsequently between 3 and 12 months (β = 5 [95% CI: 0 to 9]; p = 0.06). CONCLUSIONS: Descemet membrane endothelial keratoplasty (DMEK) results in lower posterior corneal HOAs compared with ultrathin DSAEK. Contrast sensitivity and straylight recover faster after DMEK but reach similar levels with both techniques at 1 year. Vision‐related QOL improved significantly after surgery, but did not differ between both techniques

Future directions in managing aniridia-associated keratopathy

Congenital aniridia is a panocular disorder that is typically characterized by iris hypoplasia and aniridia-associated keratopathy (AAK). AAK results in the progressive loss of corneal transparency and thereby loss of vision. Currently, there is no approved therapy to delay or prevent its progression, and clinical management is challenging because of phenotypic variability and high risk of complications after interventions; however, new insights into the molecular pathogenesis of AAK may help improve its management. Here, we review the current understanding about the pathogenesis and management of AAK. We highlight the biological mechanisms involved in AAK development with the aim to develop future treatment options, including surgical, pharmacological, cell therapies, and gene therapies

Development of machine learning models to predict posterior capsule rupture based on the EUREQUO registry

Purpose: To evaluate the performance of different probabilistic classifiers to predict posterior capsule rupture (PCR) prior to cataract surgery. Methods: Three probabilistic classifiers were constructed to estimate the probability of PCR: a Bayesian network (BN), logistic regression (LR) model, and multi‐layer perceptron (MLP) network. The classifiers were trained on a sample of 2 853 376 surgeries reported to the European Registry of Quality Outcomes for Cataract and Refractive Surgery (EUREQUO) between 2008 and 2018. The performance of the classifiers was evaluated based on the area under the precision‐recall curve (AUPRC) and compared to existing scoring models in the literature. Furthermore, direct risk factors for PCR were identified by analysing the independence structure of the BN. Results: The MLP network predicted PCR overall the best (AUPRC 13.1 ± 0.41%), followed by the BN (AUPRC 8.05 ± 0.39%) and the LR model (AUPRC 7.31 ± 0.15%). Direct risk factors for PCR include preoperative best‐corrected visual acuity (BCVA), year of surgery, operation type, anaesthesia, target refraction, other ocular comorbidities, white cataract, and corneal opacities. Conclusions: Our results suggest that the MLP network performs better than existing scoring models in the literature, despite a relatively low precision at high recall. Consequently, implementing the MLP network in clinical practice can potentially decrease the PCR rate

Anesthesia techniques and the risk of complications as reflected in the European Registry of Quality Outcomes for Cataract and Refractive Surgery

Purpose: To determine the trends in anesthesia techniques for cataract surgery over the past decade and their relationship to surgical complications. Setting: Clinics affiliated with the European Registry of Quality Outcomes for Cataract and Refractive Surgery (EUREQUO). Design: Retrospective cross-sectional register-based study. Methods: Variables include patient demographics, visual acuity, ocular comorbidities, surgery characteristics, intraoperative complications, and postoperative complications for the study period from January 2008, to December 2018. The anesthesia methods registered in the EUREQUO and included in the study are topical, combined topical and intracameral, sub-Tenon, regional, and general anesthesia. Multivariate logistic regression models for each complication were constructed to estimate the adjusted odds ratio (OR) and 95% CIs. Results: Complete data were available of 1 354 036 cataract surgeries. Topical anesthesia increased significantly over time (from 30% to 76%, P < .001). Sub-Tenon and regional anesthesia decreased (from 27% and 38% to 16% and 6%, respectively, P < .001), and general and combined topical and intracameral anesthesia remained stable (around 2%). Sub-Tenon (OR, 0.80; 95% CI, 0.71-0.91, P < .001), regional (0.74; 95% CI, 0.71-0.78, P < .001), general (0.53; 95% CI, 0.50-0.56, P < .001), and intracameral anesthesia (0.76; 95% CI, 0.64-0.90, P = .001) carried a significantly decreased risk of posterior capsule rupture (PCR), with and without dropped nucleus, compared with topical anesthesia. The risk of endophthalmitis was significantly lower with regional anesthesia compared with topical anesthesia (OR, 0.60; 95% CI, 0.44-0.82, P = .001). Conclusions: The use of topical anesthesia for cataract surgery increased over time. Topical anesthesia is associated with an increased risk of PCR with and without dropped nucleus, and endophthalmitis

A single-cell RNA-seq analysis unravels the heterogeneity of primary cultured human corneal endothelial cells

Abstract The cornea is a transparent and avascular tissue located in front of the eye. Its inner surface is lined by a monolayer of corneal endothelial cells (CECs), which maintain the cornea transparency. CECs remain arrested in a non-proliferative state and damage to these cells can compromise their function leading to corneal opacity. The primary culture of donor-derived CECs is a promising cell therapy. It confers the potential to treat multiple patients from a single donor, alleviating the global donor shortage. Nevertheless, this approach has limitations preventing its adoption, particularly culture protocols allow limited expansion of CECs and there is a lack of clear parameters to identify therapy-grade CECs. To address this limitation, a better understanding of the molecular changes arising from the primary culture of CECs is required. Using single-cell RNA sequencing on primary cultured CECs, we identify their variable transcriptomic fingerprint at the single cell level, provide a pseudo-temporal reconstruction of the changes arising from primary culture, and suggest markers to assess the quality of primary CEC cultures. This research depicts a deep transcriptomic understanding of the cellular heterogeneity arising from the primary expansion of CECs and sets the basis for further improvement of culture protocols and therapies

Single-Pass Dissection of Ultrathin Organ-Cultured Endothelial Lamellae Using an Innovative Microkeratome System

Purpose: To determine the feasibility, dissection accuracy, and endothelial viability of ultrathin endothelial lamellae harvested from organ-cultured corneas using a single-pass with an innovative motor-driven linear microkeratome system. Methods: Forty-eight (n = 48) paired organ-cultured human corneas were randomly assigned to dissection (study eyes, n = 24) with fellow eyes serving as the control (fellow eyes, n = 24). After organ culture and deswelling in a medium containing 6% dextran, endothelial lamellae with a target thickness &lt;=100 µm were dissected using a motor-driven linear microkeratome system (SLc, Gebauer, Neuhausen, Germany) equipped with 400-µm (n = 4), 450-µm (n = 10), 500-µm (n = 5), or 550-µm (n = 5) heads. Central corneal thickness (CCT) and posterior and anterior lamellar thicknesses were measured using ultrasound pachymetry (Pachette 3; DGH Technology Inc, PA) and anterior segment optical coherence tomography (Casia SS-1000; Tomey, Nagoya, Japan). Endothelial viability [endothelial cell density (ECD)] was measured using trypan vital staining. Results: CCT measured 595 ± 66 µm (n = 48) on arrival, 846 ± 131 µm (n = 48) after organ culture, and 565 ± 58 µm (n = 48) after deturgescence. CCT did not differ between study and control eyes. Posterior lamellar thickness measured 88 ± 18 µm (n = 24) immediately after dissection, 126 ± 30 µm (n = 24) 1 hour after dissection, and 131 ± 41 µm (n = 24) 2.3 ± 0.6 days after dissection. ECD measured 2637 ± 264 cells per square millimeter (n = 48) on arrival, 2524 ± 232 cells per square millimeter (n = 48) after organ culture, 2493 ± 253 cells per square millimeter (n = 48) after dissection, and 2311 ± 218 cells per square millimeter (n = 48) 2.3 ± 0.6 days after dissection. ECD did not differ between study and control eyes at all time points. Conclusions: Single-pass motor-driven linear microkeratome dissection provides an accurate and safe alternative for harvesting ultrathin endothelial lamellae from organ-cultured donor corneas