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.

Belgian Endothelial Surgical Transplant of the Cornea (BEST cornea) protocol: clinical and patient-reported outcomes of Ultra-Thin Descemet Stripping Automated Endothelial Keratoplasty (UT-DSAEK) versus Descemet Membrane Endothelial Keratoplasty (DMEK) - a multicentric, randomised, parallel group pragmatic trial in corneal endothelial decompensation.

OBJECTIVES: Corneal blindness is the third most frequent cause of blindness globally. Damage to the corneal endothelium is a leading indication for corneal transplantation, which is typically performed by lamellar endothelial keratoplasty. There are two conventional surgical techniques: Ultra-Thin Descemet Stripping Automated Endothelial Keratoplasty (UT-DSAEK) and Descemet Membrane Endothelial Keratoplasty (DMEK). The purpose of this study is to compare both techniques. METHODS AND ANALYSIS: The trial compares UT-DSAEK and DMEK in terms of clinical and patient reported outcomes using a pragmatic, parallel, multicentric, randomised controlled trial with 1:1 allocation with a sample size of 220 participants across 11 surgical centres. The primary outcome is the change in best-corrected visual acuity at 12 months. Secondary outcomes include corrected and uncorrected vision, refraction, proportion of high vision, quality of life (EQ-5D-5L and VFQ25), endothelial cell counts and corneal thickness at 3, 6 and 12 months follow-up appointments. Adverse events will also be compared 12 months postoperatively. ETHICS AND DISSEMINATION: The protocol was reviewed by ethical committees of 11 participating centres with the sponsor centre issuing the final definitive approval. The results will be disseminated at clinical conferences, by patient partner groups and open access in peer-reviewed journals. GOVERNANCE OF THE TRIAL: Both, trial management group and trial steering committee, are installed with representatives of all stakeholders involved including surgeons, corneal bankers, patients and external experts. TRIAL REGISTRATION NUMBER: NCT05436665.

DNA extraction protocol impacts ocular surface microbiome profile.

Purpose: The aim of this study is to provide a reference frame to allow the comparison and interpretation of currently published studies on 16S ribosomal ribonucleic acid amplicon sequencing of ocular microbiome samples using different DNA extraction protocols. Alongside, the quantitative and qualitative yield and the reproducibility of different protocols has been assessed. Methods: Both eyes of 7 eligible volunteers were sampled. Five commercially available DNA extraction protocols were selected based on previous publications in the field of the ocular surface microbiome and 2 host DNA depletion protocols were added based on their reported effective host DNA depletion without significant reduction in bacterial DNA concentration. The V3-V4 region of the 16S rRNA gene was targeted using Illumina MiSeq sequencing. The DADA2 pipeline in R was used to perform the bio-informatic processing and taxonomical assignment was done using the SILVA v132 database. The Vegdist function was used to calculate Bray-Curtis distances and the Galaxy web application was used to identify potential metagenomic biomarkers via linear discriminant analysis Effect Size (LEfSe). The R package Decontam was applied to control for potential contaminants. Results: Samples analysed with PowerSoil, RNeasy and NucleoSpin had the highest DNA yield. The host DNA depletion kits showed a very low microbial DNA yield; and these samples were pooled per kit before sequencing. Despite pooling, 1 of both failed to construct a library.Looking at the beta-diversity, clear microbial compositional differences - dependent on the extraction protocol used - were observed and remained present after decontamination. Eighteen genera were consistently retrieved from the ocular surface of every volunteer by all non-pooled extraction kits and a comprehensive list of differentially abundant bacteria per extraction method was generated using LefSe analysis. Conclusion: High-quality papers have been published in the field of the ocular surface microbiome but consensus on the importance of the extraction protocol used are lacking. Potential contaminants and discriminative genera per extraction protocol used, were introduced and a reference frame was built to facilitate both the interpretation of currently published papers and to ease future choice - making based on the research question at hand.

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.

Posterior chamber toric implantable collamer lenses vs LASIK for myopia and astigmatism: systematic review.

This systematic review compares the visual and refractive outcome of laser in situ keratomileusis with (toric) implantable collamer lens (ICL) in the treatment of myopic astigmatism. An electronic literature search led to 19 comparative articles. Refractive outcome, efficacy, safety, predictability, and stability as well as differences in contrast sensitivity and higher-order aberrations (HOAs) were analyzed for moderate (-3 to -6 diopters [D]) and high (≥-6 D) myopia. Results were either significantly in favor of (toric)-ICL or equal. Fewer HOAs and better contrast sensitivity after (toric)-ICL seem to be the largest asset in its refractive and clinical superiority. However, longer follow-up studies are indicated, specifically for systematically comparing long-term adverse effects.

The Effect of Topical Anesthetics on 16S Ribosomal Ribonucleic Acid Amplicon Sequencing Results in Ocular Surface Microbiome Research.

PURPOSE: To clarify the short-term effect of topical anesthetics on 16S ribosomal ribonucleic acid amplicon sequencing results in ocular surface microbiome research. METHODS: Both eyes of 24 eligible volunteers undergoing general anesthesia were sampled. Before sampling, a drop of artificial tears or a drop of topical anesthetic was applied in a randomized way. By using artificial tears as a control, we assured blinding of the executer and took a potential diluting effect into account. Bacterial DNA was extracted using the QIAGEN RNeasy PowerMicrobiome Kit with specific adaptations. Amplified DNA was sequenced with the Illumina MiSeq sequencing platform. RESULTS: Four sample pairs were excluded due to low yield of bacterial DNA. In the remaining 20 sample pairs, no differences were observed with topical anesthetics at the levels of amplicon sequence variants (ASVs), phylum, genera, or alpha and beta diversity. Weighted UniFrac distance confirmed that the intraindividual distance between the right and left eye was smaller than the effect of the topical anesthetic. Interestingly, however, we identified Cutibacterium as a potential discriminative biomarker for topical anesthetic use. Overall, a significantly higher number of observed reads were assigned to genera with Gram-positive characteristics. CONCLUSIONS: Based on our targeted, double-blinded, within-subject study, topical anesthetics do not affect the overall sequencing results but display a specific effect on Cutibacterium. When comparing research results, the impact of topical anesthetics on prevalence and abundance of Cutibacterium should be considered. TRANSLATIONAL RELEVANCE: Understanding and standardization of sampling techniques are indispensable to properly execute clinical microbiome research.

Putting drug resistant epithelial herpes keratitis in the spotlight: A case series.

PURPOSE: To strengthen the sparse evidence on acyclovir (ACV) resistance, especially in recalcitrant herpetic keratitis (HK), by describing the clinical course of 3 genotypically proven ACV resistant HK cases. An overview of mechanisms of resistance and therapeutic options currently available to ophthalmologists is provided based upon recent literature search. OBSERVATIONS: Resistance to ACV due to known mutations in the gene encoding the viral thymidine kinase was confirmed in 2 cases, and a novel mutation in the UL23 gene (N202K) conferring phenotypical resistance to ACV was discovered in 1 case. Three unique therapeutic strategies finally led to epithelial closure. CONCLUSIONS: The novel thymidine kinase mutation (N202K) should be considered to infer resistance to all molecules requiring activation by the viral thymidine kinase. Current topical alternatives in the ophthalmologist's armamentarium include trifluridine 1%, foscarnet 1,2%-1,4% or cidofovir 0,2-0,5%. Epithelial debridement, high-frequency dosing and reduction of immunosuppression are useful adjuncts. IMPORTANCE: Clinicians should perform epithelial debridement in recalcitrant HK, allowing geno- and phenotypically guided therapy, even without a history of long-term anti-viral prophylaxis or recurrent HK. This report provides mandatory knowledge allowing the reader to comprehend how therapy should be altered based upon these results. To the best of our knowledge, successful treatment of proven ACV resistant HK with topical foscarnet has not yet previously been published.Furthermore, this paper highlights a lack of controlled studies investigating alternative topical treatments in case of viral resistance, offering opportunities for future research.

Late-onset toxic anterior segment syndrome after possible aluminum-contaminated and silicon-contaminated intraocular lens implantation.

PURPOSE: To describe an outbreak of late-onset toxic anterior segment syndrome (TASS) after the implantation of a specific hydrophilic acrylic intraocular lens (IOL). SETTING: University Hospitals of Leuven, Belgium. DESIGN: Retrospective, single-center, observational study. METHODS: All eyes undergoing cataract surgery with a monofocal, toric, or enhanced depth-of-focus (EDoF) Synthesis (Cutting Edge) IOL between August 2019 and March 2020 were reviewed. Data were collected on the surgical procedure, postoperative course, time until onset of symptoms, clinical features, and additional treatments. A laboratory surface analysis of all 3 IOL subtypes was performed in the Intermountain Ocular Research Center at the University of Utah, USA. Furthermore, other possible causes of prolonged postoperative inflammation rather than the IOL itself were investigated. RESULTS: Among the 203 eyes included, 28 TASS cases were identified (13.8%), among which 25 received a monofocal IOL, and 3 received an EDoF IOL. The mean time until onset was 28.9 (±19.9) days. Patients presented with anterior chamber cells (92.9%), deposits on the IOL (57.1%), or fibrinous inflammation (35.7%). 4 eyes (14.3%) underwent a surgical intervention, whereas 24 eyes showed a resolution of inflammation with topical therapy alone. Laboratory analysis showed the presence of both aluminum and silicon particles on the monofocal IOL, silicon particles only on the EDoF IOL, and no particles on the toric IOL surface. CONCLUSIONS: This report describes an outbreak of atypical, late-onset TASS after cataract surgery, possibly correlated with aluminum and silicon contamination of the IOL surfaces.

Alternative indications for corneal crosslinking.

Corneal crosslinking (CXL) is the current mainstay treatment for progressive keratoconus. In the past 15 years, a variety of other indications have been tested. A systematic review was conducted to examine these alternative indications for CXL. In total, 143 papers on crosslinking as a treatment for infectious keratitis, bullous keratopathy, pellucid marginal degeneration, and postlaser in situ keratomileusis (LASIK) ectasia and as a way to improve vision either on its own or in combination with other interventions were included. Post-LASIK ectasia is a definite indication for crosslinking. Surprisingly, only limited research has been performed on pellucid marginal degeneration, with no randomized trials available to date. Other interesting applications are the combined use of refractive lasers and crosslinking for suspicious or ectatic corneas and crosslinking as a standalone intervention for minor refractive errors. CXL might offer a solution for refractory bacterial keratitis. In bullous keratopathy, it seems to offer only a transient benefit.

Current knowledge on the human eye microbiome: a systematic review of available amplicon and metagenomic sequencing data.

Insights in the ocular surface microbiome are still at an early stage and many more questions remain unanswered compared with other human-associated microbial communities. The current knowledge on the human microbiome changed our viewpoint on bacteria and human health and significantly enhanced our understanding of human pathophysiology. Also in ocular medicine, microbiome research might impact treatment. Here, we summarize the current knowledge on ocular microbiome research with a particular focus on potential confounding factors and their effects on microbiome composition. Moreover, we present the ocular surface core microbiome based on current available data and defined it as genera present in almost half of the published control cohorts with a relative abundance of at least 1%.

How a Devastating Case of Acanthamoeba Sclerokeratitis Ended up with Serious Systemic Sequelae.

A 35-year old soft contact lens wearer with a proven bilateral Acanthamoeba keratitis developed a nodular scleritis. Based on the stepladder approach described by Iovieno et al. [Ophthalmology. 2014 Dec;121(12):2340-7], nonsteroidal anti-inflammatory drugs, methylprednisolone, and later azathioprine were added to the antiamoebic treatment. Unfortunately, there was further deterioration and an endophthalmitis developed. Unbearable pain and concerns of spread to the brain urged an enucleation. Histopathological examination confirmed Acanthamoeba cysts in the cornea, sclera, retina, choroid, and vitreous body. As a side effect of the immunosuppressive treatment, the patient developed myopathy, pulmonary aspergillosis, and an avascular necrosis of the hip. Scleritis is a devastating complication of Acanthamoeba keratitis with a poor prognosis and a high enucleation rate. Acanthamoeba sclerokeratitis is, due to cyst-free biopsies, mostly assigned to an immune-mediated mechanism, justifying the use of immunosuppressive treatment. Scleritis in our case contributed to the extracorneal spread of Acanthamoeba. Our case is the first documented extracorneal spread of Acanthamoeba without previous surgery. Extracorneal spread of Acanthamoeba should be considered, even in the case of false-negative biopsies. We strongly recommend serial sections of the retrieved scleral specimen in case of negative histopathological examination to exclude an infection. Even when an immune-mediated scleritis is suspected, systemic immunosuppressive treatment should always be used with the greatest caution. Awareness of the side effects and monitoring by an experienced physician is mandatory.

Atypical Corneal Ectasia Associated With Vitamin C Deficiency.

PURPOSE: To demonstrate a possible correlation between corneal ectasia and vitamin C deficiency. METHODS: Case series. RESULTS: This case series covers 3 patients with atypical features of corneal ectasia. All 3 had a peculiar general history and visited our tertiary ophthalmology department complaining about decreased visual acuity. Corneal tomography by Scheimpflug imaging (Pentacam) indicated an irregular astigmatism congruent with a corneal ectasia. A blood test diagnosed vitamin C deficiency. CONCLUSIONS: To the best of our knowledge, this is the first time a possible correlation between corneal ectasia and vitamin C deficiency is established. Although more research is of course of the essence, it proves useful to determine vitamin C plasma levels in patients presenting with atypical ectasia. To the extent that vitamin C deficiency is indeed diagnosed, it should be substituted orally.

Trabeculectomy With Moorfields Conjunctival Closure Technique Offers Safety Without Astigmatism Induction.

PURPOSE: To evaluate the safety profile and possible change in corneal astigmatism following trabeculectomy with a fornix-based conjunctival flap which is closed with 4 corneal groove-embedded sutures. MATERIALS AND METHODS: Patients scheduled for a primary trabeculectomy were included in this single center, prospective trial between February and April 2013. Refractive status was assessed with an automated refractokeratometer preoperatively and at months 1, 3, 6, and 18 postoperatively, together with clinical assessment of intraocular pressure, visual acuity, postoperative complications, and medication use. Preoperative and postoperative variables were compared using paired samples t tests and vector analysis for corneal astigmatism change was performed. RESULTS: Forty-four eyes of 44 patients were included. Vector analysis showed a transient significant with-the-rule shift in astigmatism without influence on spherical equivalent. Visual acuity was transiently reduced in the first month but recovered to preoperative values with no need to change optical correction. Two patients developed postoperative wound leakage, which was successfully treated with a bandage corneoscleral contact lens. CONCLUSIONS: Trabeculectomy with a fornix-based conjunctival flap closed by 4 corneal groove-embedded sutures results in a low complication rate. This safe suturing technique induces a transient shift of with-the-rule astigmatism, reverting to the preoperative values within 3 months of surgery. Adjustments to refractive correction are recommended to be postponed until after this period.

The Effect of Trabeculectomy on Astigmatism.

PURPOSE: To investigate the change in corneal astigmatism after trabeculectomy. PATIENTS AND METHODS: Between January and April 2012, patients who underwent a primary trabeculectomy were enrolled in this prospective study. We measured the visual acuity, automated keratorefractometry, and the intraocular pressure preoperatively and postoperatively at 1, 3, and 6 months. Changes in astigmatism were quantified using the vector analysis described by Cravy. A Friedman test and a linear model for longitudinal measures were used to compare changes in the refraction and the intraocular pressure. A binomial test was used to compare the proportion of eyes with a shift in astigmatism with or against-the-rule. RESULTS: A total of 47 eyes (47/48 patients) were included for analysis. The mean (±SD) intraocular pressure decreased from 17.5 ± 5.4 mmHg preoperatively to 9.8 ± 4.0 mmHg after 6 months (P<0.001). At this time-point, 32/47 eyes showed a shift in astigmatism with-the-rule (P=0.02), with a median difference in cylinder of +0.50 D (range, 0 to 4 D) (P=0.004). The mean (±SD) axis of the positive cylinder changed from 169 ± 148 to 135 ± 146 degrees after 6 months (P=0.12) and the mean (±SD) spherical equivalent changed from -0.47 ± 2.27 to -0.07 ± 1.93 D (P=0.15). The mean (±SD) logMAR was 0.17 ± 0.22 preoperatively and 0.14 ± 0.14 after 6 months (P=0.9). CONCLUSIONS: Trabeculectomy induced a small but statistically significant shift in astigmatism with-the-rule after 6 months. The spherical equivalent did not change compared with the preoperative value. Most often, glasses will not need to be changed after trabeculectomy.