Cost-effectiveness of the ADVISE trial: An intraoperative OCT protocol in DMEK surgery.

The intraoperative optical coherence tomography (iOCT) is recently introduced in Descemet membrane endothelial keratoplasty (DMEK) surgery, which aims to increase clinical performance and surgery safety. However, the acquisition of this modality is a substantial investment. The objective of this paper is to report on the cost-effectiveness of an iOCT-protocol in DMEK surgery with the Advanced Visualization in Corneal Surgery Evaluation (ADVISE) trial. This cost-effectiveness analysis uses data 6 months postoperatively from the multicentre prospective randomized clinical ADVISE trial. Sixty-five patients were randomized to usual care (n = 33) or the iOCT-protocol (n = 32). Quality-Adjusted Life Years (EQ-5D-5L), Vision-related Quality of Life (NEI-VFQ-25) and self-administered resources questionnaires were administered. Main outcome is the incremental cost-effectiveness ratio (ICER) and sensitivity analyses. The iOCT protocol reports no statistical difference in ICER. For the usual care group compared with the iOCT protocol, respectively, the mean societal costs are €5027 compared with €4920 (Δ€107). The sensitivity analyses report the highest variability on time variables. This economic evaluation learned that there is no added value in quality of life or cost-effectiveness in using the iOCT protocol in DMEK surgery. The variability of cost variables depends on the characteristics of an eye clinic. The added value of iOCT could gain incrementally by increasing surgical efficiency, and aiding in surgical decision-making.

Video Grading of Descemet Membrane Endothelial Keratoplasty Surgery to Identify Surgeon Risk Factors for Graft Detachment and Rebubbling: A Post Hoc Observational Analysis of the Advanced Visualization In Corneal Surgery Evaluation Trial.

PURPOSE: The aim of this study was to explore video-graded intraoperative risk factors for graft detachment (GD) and rebubbling in Descemet membrane endothelial keratoplasty surgery. METHODS: A post hoc analysis of 65 eyes of 65 pseudophakic subjects with Fuchs endothelial dystrophy that underwent Descemet membrane endothelial keratoplasty surgery as part of the Advanced Visualization In Corneal Surgery Evaluation trial. All surgical recordings were assessed by 2 graders using a structured assessment form. A multinominal regression was performed to estimate the independent effect of video-graded intraoperative factors on the incidence of GD and rebubbling. Secondary outcomes are corrected distance visual acuity and endothelial cell density. RESULTS: In total, 33 GDs were recorded, of which 17 required rebubbling. No significant predictors for GD or rebubbling were identified. However, the results revealed 2 clinically relevant patterns. An unfavorable graft configuration (ie, wrinkled, tight scroll, or taco-shaped) and a gas-bubble size smaller than the graft diameter were associated with an increased risk of GD [odds ratio (OR) 2.5 and OR 2.26, respectively] and rebubbling (OR 2.0 and OR 2.60, respectively). Inversely, a larger gas-bubble size was associated with a reduced risk of GD (OR 0.37) and rebubbling (OR 0.36). At 3 and 6 months postoperatively, corrected distance visual acuity was poorer in subjects requiring a rebubbling and endothelial cell density loss was higher in subjects with a partial GD. CONCLUSIONS: Our analysis revealed that the gas-bubble size and graft shape/geometry seem to be relevant clinical factors for GD and rebubbling, whereas descemetorhexis difficulty, degree of graft manipulation, graft overlap, and surgical iridectomy were not associated with an increased risk.

Establishing a Biomarker for the Prediction of Short-Term Graft Detachment After Descemet Membrane Endothelial Keratoplasty.

PURPOSE: The purpose of this study was to investigate the predictive value of pachymetry mapping 1 day after Descemet membrane endothelial keratoplasty (DMEK) as a biomarker for early graft detachment. METHODS: This was a post hoc analysis of 65 pseudophakic subjects with Fuchs endothelial dystrophy who underwent DMEK surgery between December 2018 and April 2021 as part of the Advanced Visualization In Corneal Surgery Evaluation international multicenter randomized controlled trial. One eye per patient was included. Preoperatively and 1 day postoperatively, patients underwent anterior segment optical coherence tomography imaging. Using a grid consisting of 25 zones (ie, pachymetry map), corneal thickness and presence of a graft detachment were mapped for each patient. Detachments of any size were considered, regardless of subsequent clinical interventions. Missing data were imputed and subsequently divided into a training and test set. Two prediction methods were evaluated: one model based on absolute corneal thickness and a regression model. RESULTS: A total of 65 eyes were included for analysis of which 33 developed any form of graft detachment. Preoperatively, no significant differences were observed between the groups ( P = 0.221). Corneal thickness in the corneal zones with a detached graft was significantly increased compared with corneal zones with an attached graft ( P < 0.001). The regression prediction model had an area under the curve of 0.87 (sensitivity: 0.79 and specificity: 0.75), whereas the absolute thickness cutoff model only reached 0.65. CONCLUSIONS: Pachymetry mapping 1 day after DMEK was predictive for early graft detachment, and the prediction model had a good to excellent performance. This aids in identifying patients at risk for graft detachment and subsequent tailored postoperative care.

Automatic evaluation of graft orientation during Descemet membrane endothelial keratoplasty using intraoperative OCT.

Correct Descemet Membrane Endothelial Keratoplasty (DMEK) graft orientation is imperative for success of DMEK surgery, but intraoperative evaluation can be challenging. We present a method for automatic evaluation of the graft orientation in intraoperative optical coherence tomography (iOCT), exploiting the natural rolling behavior of the graft. The method encompasses a deep learning model for graft segmentation, post-processing to obtain a smooth line representation, and curvature calculations to determine graft orientation. For an independent test set of 100 iOCT-frames, the automatic method correctly identified graft orientation in 78 frames and obtained an area under the receiver operating characteristic curve (AUC) of 0.84. When we replaced the automatic segmentation with the manual masks, the AUC increased to 0.92, corresponding to an accuracy of 86%. In comparison, two corneal specialists correctly identified graft orientation in 90% and 91% of the iOCT-frames.

Bilateral posterior lamellar corneal transplant surgery in an infant of 17 weeks old: Surgical challenges and the added value of intraoperative optical coherence tomography.

This study aimed to describe the surgical challenges, management, and value of intraoperative optical coherence tomography in a case of a bilateral Descemet Stripping Automated Endothelial Keratoplasty corneal transplantation at 17 weeks of age for the treatment of severe posterior polymorphous corneal dystrophy resulting from a de novo mutation of the OVOL2-gene.

Clinical applications for intraoperative optical coherence tomography: a systematic review.

In this systematic review, we provide an overview of the current state of intraoperative optical coherence tomography (iOCT). As iOCT technology is increasingly utilized, its current clinical applications and potential uses warrant attention. Here, we categorize the findings of various studies by their respective fields, including the use of iOCT in vitreoretinal surgery, corneal surgery, glaucoma surgery, cataract surgery, and pediatric ophthalmology. The trend observed in recent decades towards performing minimally invasive ophthalmic surgery has caused practitioners to recognize the limitations of using a conventional surgical microscope for intraoperative visualization. Thus, the superior visualization provided by iOCT can improve the safety of these surgical techniques and promote the development of new minimally invasive ophthalmic surgeries. Landmark prospective studies found that iOCT can significantly affect surgical decision making and can cause a subsequent change in surgical strategy, and the use of iOCT has potential to improve surgical outcome. Despite these advantages, however, iOCT is still a relatively new technique, and beginning users of iOCT can encounter limitations that can preclude their reaching the full potential of iOCT and in this respect several improvements are needed.

Correction: The evaluation of a web-based tool for measuring the uncorrected visual acuity and refractive error in keratoconus eyes: A method comparison study.

[This corrects the article DOI: 10.1371/journal.pone.0256087.].

The evaluation of a web-based tool for measuring the uncorrected visual acuity and refractive error in keratoconus eyes: A method comparison study.

PURPOSE: To evaluate the outcome of a web-based digital assessment of visual acuity and refractive error, compared to a conventional supervised assessment, in keratoconus patients with complex refractive errors. MATERIAL AND METHODS: Keratoconus patients, aged 18 to 40, with a refractive error between -6 and +4 diopters were considered eligible. An uncorrected visual acuity and an assessment of refractive error was taken web-based (index test) and by manifest refraction (reference test) by an optometrist. Corrected visual acuity was assessed with the prescription derived from both the web-based tool and the manifest refraction. Non-inferiority was defined as the 95% limits-of-agreement (95%LoA) of the differences in spherical equivalent between the index and reference test not exceeding +/- 0.5 diopters. Agreement was assessed by a Bland-Altman analyses. RESULTS: A total of 100 eyes of 50 patients were examined. The overall mean difference of the uncorrected visual acuity measured -0.01 LogMAR (95%LoA:-0.63-0.60). The variability of the differences decreased in the better uncorrected visual acuity subgroup (95%LoA:-0.25-0.55). The overall mean difference in spherical equivalent between the index and reference test exceeded the non-inferiority margin: -0.58D (95%LoA:-4.49-3.33, P = 0.008). The mean differences for myopic and hyperopic subjects were 0.09 diopters (P = 0.675) and -2.06 diopters (P<0.001), respectively. The corrected visual acuities attained with the web-based derived prescription underachieved significantly (0.22±0.32 logMAR vs. -0.01±0.13 LogMAR, P <0.001). CONCLUSIONS: Regarding visual acuity, the web-based tool shows promising results for remotely assessing visual acuity in keratoconus patients, particularly for subjects within a better visual acuity range. This could provide physicians with a quantifiable outcome to enhance teleconsultations, especially relevant when access to health care is limited. Regarding the assessment of the refractive error, the web-based tool was found to be inferior to the manifest refraction in keratoconus patients. This study underlines the importance of validating digital tools and could serve to increase overall safety of the web-based assessments by better identification of outlier cases.

Intraoperative Optical Coherence Tomography-Assisted Descemet Membrane Endothelial Keratoplasty: Toward More Efficient, Safer Surgery.

PURPOSE: To evaluate the clinical value of intraoperative optical coherence tomography (iOCT) and prolonged overpressure in Descemet membrane endothelial keratoplasty for surgical safety, efficiency, and outcome. METHODS: All Descemet membrane endothelial keratoplasties performed by the same surgeon from November 2016 through April 2018 at the University Medical Center Utrecht were included, including 6 months of follow-up. The primary outcome was the prevalence of adverse events, and the secondary outcomes included critical decision-making and surgery time. Surgeries that included prolonged (ca. 12 minutes) overpressurization of the globe were classified as group 1, and those without prolonged overpressurization of the globe were classified as group 2. In all cases, iOCT was used to determine the graft orientation, apposition, and assessment of interface fluid. RESULTS: A total of 38 cases were included for analysis. In groups 1 and 2, 7 (43.6%) and 4 (18.1%) adverse events, respectively, were recorded (P = 0.29). Specifically, in groups 1 and 2, 4 and 3 cases, respectively, required rebubbling because of graft dislocation (P = 0.15). In 43% of surgeries, iOCT proved to be of value for surgical decision-making. Surgery time differed significantly between groups 1 and 2 (P < 0.001) and was the result of a shortened pressurization time in group 2. CONCLUSIONS: iOCT provides a direct assessment of the graft orientation and apposition, allowing the surgeon to refrain from prolonged pressurization of the globe after graft insertion. Optimizing the surgical protocol using iOCT can lead to a significant reduction in surgery time without compromising surgical safety or outcome.

Validation of an Independent Web-Based Tool for Measuring Visual Acuity and Refractive Error (the Manifest versus Online Refractive Evaluation Trial): Prospective Open-Label Noninferiority Clinical Trial.

BACKGROUND: Digital tools provide a unique opportunity to increase access to eye care. We developed a Web-based test that measures visual acuity and both spherical and cylindrical refractive errors. This test is Conformité Européenne marked and available on the Easee website. The purpose of this study was to compare the efficacy of this Web-based tool with traditional subjective manifest refraction in a prospective open-label noninferiority clinical trial. OBJECTIVE: The aim of this study was to evaluate the outcome of a Web-based refraction compared with a manifest refraction (golden standard). METHODS: Healthy volunteers from 18 to 40 years of age, with a refraction error between -6 and +4 diopter (D), were eligible. Each participant performed the Web-based test, and the reference test was performed by an optometrist. An absolute difference in refractive error of <0.5 D was considered noninferior. Reliability was assessed by using an intraclass correlation coefficient (ICC). Both uncorrected and corrected visual acuity were measured. RESULTS: A total of 200 eyes in 100 healthy volunteers were examined. The Web-based assessment of refractive error had excellent correlation with the reference test (ICC=0.92) and was considered noninferior to the reference test. Uncorrected visual acuity was similar with the Web-based test and the reference test (P=.21). Visual acuity was significantly improved using the prescription obtained by using the Web-based tool (P<.01). The Web-based test provided the best results in participants with mild myopia (ie, <3 D), with a mean difference of 0.02 (SD 0.49) D (P=.48) and yielding a corrected visual acuity of >1.0 in 90% (n=77) of participants. CONCLUSIONS: Our results indicate that Web-based eye testing is a valid and safe method for measuring visual acuity and refractive error in healthy eyes, particularly for mild myopia. This tool can be used for screening purposes, and it is an easily accessible alternative to the subjective manifest refraction test. TRIAL REGISTRATION: Clinicaltrials.gov NCT03313921; https://clinicaltrials.gov/ct2/show/NCT03313921.

Clinical Evaluation and Validation of the Dutch Crosslinking for Keratoconus Score.

Importance: Defining keratoconus progression is fundamental in clinical decision making because crosslinking treatments are indicated when the disease is considered progressive. Currently, there is no consensus which parameters should be used to define progression. Objective: To assess and validate a novel clinical scoring system as an easy-to-use assessment tool for crosslinking treatment in patients with keratoconus. Design, Setting, and Participants: Prospective cohort study at 2 academic treatment centers. Patients with keratoconus referred between January 1, 2012, and June 30, 2014, with 2-year follow-up were included. Analysis began March 2017. Interventions: The Dutch Crosslinking for Keratoconus (DUCK) score is based on changes in 5 clinical parameters that are routinely assessed: age, visual acuity, refraction error, keratometry, and subjective patient experience. The DUCK score is derived by scoring 0 to 2 points per item, and cutoffs were determined by clinical experience. We compared the DUCK scores to the conventional 1.0-diopter increase in maximum keratometry criterion, within the last 12 months, in a longitudinal discovery and a validation cohort. Sensitivity analyses and intraitem correlations were performed. Main Outcomes and Measures: Overall treatment rate reduction and the duly withheld treatment rate. Results: A total of 504 eyes of 388 patients were available for analysis on disease progression in the course of 12 and 24 months. Baseline patient characteristics of the discovery cohort and the validation cohort were comparable in terms of age (mean [SD], 26.8 [8.3] years vs 26.3 [9.1]), sex (216 of 332 [65%] vs 123 of 172 [72%] men), and maximum keratometry (mean [SD], 53.5 [7.1] vs 52.7 [6.3]). Adhering to the DUCK score, rather than maximum keratometry, was associated with a reduction in overall treatment rate by 23% (95% CI, 18%-30%), without increasing the risk of disease progression (ie, the rate of progression for both groups was equal; ±0%). The DUCK score appears to better identify eyes that were duly withheld treatment by 35% (95% CI, 22%-49%). Conclusions and Relevance: These results provide validation of the DUCK score as a tool to determine whether a crosslinking treatment might be warranted. Compared with the conventional maximum keratometry criterion of more than 1.0 diopter, the DUCK score may better select patients who might benefit from crosslinking treatment. Potentially, it may prevent unnecessary treatments, reduce exposure to treatment risks, and improve the cost effectiveness of crosslinking.

Prospective evaluation of clinical outcomes between pre-cut corneal grafts prepared using a manual or automated technique: with one-year follow-up.

PURPOSE: Posterior lamellar corneal surgery is considered the standard of care for irreversible endothelial cell dysfunction. Pre-cut grafts can be prepared either manually (Descemet stripping endothelial keratoplasty; DSEK) or mechanically (Descemet stripping automated endothelial keratoplasty; DSAEK). We performed a head-to-head clinical comparison between DSEK and DSAEK grafts. METHODS: All DSEK and DSAEK procedures performed by two corneal specialists at the University Medical Center Utrecht from 1 January 2016 through 31 October 2016 were prospectively included. Pre-cut grafts were delivered by two eye banks, which either exclusively prepared the DSEK or DSAEK grafts. Preoperative and postoperative measurements were obtained, and all surgical events and adverse events were recorded. RESULTS: A total of 21 DSEK and 53 DSAEK procedures were included for analysis; the two groups were similar at baseline, with the exception of graft endothelial cell density, which was 2531 ± 67 versus 2748 ± 148 cells/mm2 , respectively (p < 0.001). At the one-year follow-up visit, corrected distance visual acuity and endothelial cell loss were similar between the groups. Mean pachymetry was significantly lower in the DSEK group (521 ± 39 versus 588 ± 59 µm; p < 0.001), whereas the rebubbling rate was significantly higher in the DSEK group (47.6% versus 18.9%; p = 0.001). Finally, three grafts in the DSEK group experienced failure compared to one graft in the DSAEK group (14% versus 1.9%, respectively). CONCLUSION: Manually dissected and microkeratome-dissected grafts performed similarly with respect to vision and endothelial cell loss assessed one year after surgery. The higher incidence of graft failure among manually dissected (i.e. DSEK) grafts may be attributable to reduced relative thickness compared to DSAEK grafts and/or the resulting differences in tissue handling and the surgeon's learning curve.

Autorefraction Versus Manifest Refraction in Patients With Keratoconus.

PURPOSE: To compare visual performance using autorefraction and manifest refraction assessments in patients with keratoconus and investigate whether autorefraction measurements lead to suboptimal visual performance. METHODS: Corrected distance visual acuity (CDVA) was measured in 90 eyes of 61 patients with keratoconus with both autorefraction and manifest refraction, in a random order. Maximum keratometry (Kmax), cone location, and wavefront aberration were determined with Scheimpflug tomography. The difference between the autorefraction and manifest refraction outcomes was converted to vectors and a multivariable analysis was performed to identify potential underlying causes of this difference. RESULTS: A significantly better CDVA was achieved with manifest refraction (0.06 vs 0.29 logMAR [20/23 vs 20/38 Snellen], P < .001). After vector analysis, a mean difference of 4.83 diopters was found between autorefraction and manifest refraction. Increased Kmax was strongly and significantly associated with better visual performance of manifest refraction compared to autorefraction (B = 0.496, P = .002). CONCLUSIONS: This study showed that a superior CDVA is achieved with manifest refraction compared to autorefraction in patients with keratoconus. Furthermore, the difference between the two refraction methods increases as the cornea steepens. According to this study, autorefraction is unreliable in patients with keratoconus and should be avoided. [J Refract Surg. 2018;34(1):30-34.].