Acute Bilateral Descemet Membrane Endothelial Keratoplasty Graft Rejection After the BNT162b2 mRNA COVID-19 Vaccine.

Purpose: We report a case of acute bilateral Descemet membrane endothelial keratoplasty (DMEK) rejection two weeks following BNT162b2 mRNA COVID-19 vaccine (Pfizer-BioNTech), reflecting on possible changes to the management of patients with DMEK scheduled for COVID-19 vaccination. Patients and Methods: A 94-year-old woman with Fuchs' endothelial dystrophy who underwent DMEK 24 months earlier (right eye) and 20 months earlier (left eye) demonstrated bilateral graft rejection two weeks after the first dose of COVID-19 vaccine. Standard treatment regimen was followed, and clinical status documented with slit-lamp examination and swept-source optical coherence tomography throughout. Results: Preoperative best corrected visual acuity (BCVA) and corneal thickness (CT) were 0.3 and 679µm right eye and 0.2 and 668µm left eye. Postoperative BCVA and CT were 0.7 and 559µm right eye and 0.4 and 590µm left eye. Standard treatment regimen consisted of dexamethasone/tobramycin and ketorolac, four times daily. At one month, both preparations were discontinued, replaced by dexamethasone 0.1% four times daily. At three months, this was tapered to once daily. Post-rejection, BCVA and CT were 0.2 and 710µm right eye and 0.3 and 710µm left eye. Treatment was with dexamethasone/tobramycin six times daily. Poor response resulted in re-DMEK transplantation, starting in the left eye. At one-month follow-up, BCVA and CT were 0.5 and 538µm right eye and 0.63 and 504µm left eye. Conclusion: We report the first acute bilateral DMEK graft rejection after a single dose of COVID-19 vaccine. We recommend clinicians exercise vigilance and consider dexamethasone 0.1% during the vaccination period.

Assessment of Anterior Uveitis Through Anterior-Segment Optical Coherence Tomography and Artificial Intelligence-Based Image Analyses.

Purpose: The purpose of this study was to develop an automated artificial intelligence (AI) based method to quantify inflammation in the anterior chamber (AC) using anterior-segment optical coherence tomography (AS-OCT) and to explore the correlation between AI assisted AS-OCT based inflammation analyses and clinical grading of anterior uveitis by Standardization of Uveitis Nomenclature (SUN). Methods: A prospective double blinded study of AS-OCT images of 32 eyes of 19 patients acquired by Tomey CASIA-II. OCT images were analyzed with proprietary AI-based software. Anatomic boundaries of the AC were segmented automatically by the AI software and Spearman's rank correlation between parameters related to AC cellular inflammation were calculated. Results: No significant (p = 0.6602) differences were found between the analyzed AC areas between samples of the different SUN grading, suggesting accurate and unbiased border detection/AC segmentation. Segmented AC areas were processed by the AI software and particles within the borders of AC were automatically counted by the software. Statistical analysis found significant (p < 0.001) correlation between clinical SUN grading and AI software detected particle count (Spearman ρ = 0.7077) and particle density (Spearman ρ = 0.7035). Significant (p < 0.001) correlation (Pearson's r = 0.9948) between manually and AI detected particles was found. No significant (p = 0.8080) difference was found between the sizes of the AI detected particles for all studies. Conclusions: AI-based image analysis of AS-OCT slides show significant and independent correlation with clinical SUN assessment. Translational Relevance: Automated AI-based AS-OCT image analysis suggests a noninvasive and quantitative assessment of AC inflammation with clear potential application in early detection and management of anterior uveitis.

Corneal pachymetry by AS-OCT after Descemet's membrane endothelial keratoplasty.

Corneal thickness (pachymetry) maps can be used to monitor restoration of corneal endothelial function, for example after Descemet's membrane endothelial keratoplasty (DMEK). Automated delineation of the corneal interfaces in anterior segment optical coherence tomography (AS-OCT) can be challenging for corneas that are irregularly shaped due to pathology, or as a consequence of surgery, leading to incorrect thickness measurements. In this research, deep learning is used to automatically delineate the corneal interfaces and measure corneal thickness with high accuracy in post-DMEK AS-OCT B-scans. Three different deep learning strategies were developed based on 960 B-scans from 50 patients. On an independent test set of 320 B-scans, corneal thickness could be measured with an error of 13.98 to 15.50 µm for the central 9 mm range, which is less than 3% of the average corneal thickness. The accurate thickness measurements were used to construct detailed pachymetry maps. Moreover, follow-up scans could be registered based on anatomical landmarks to obtain differential pachymetry maps. These maps may enable a more comprehensive understanding of the restoration of the endothelial function after DMEK, where thickness often varies throughout different regions of the cornea, and subsequently contribute to a standardized postoperative regime.

Quantifying Graft Detachment after Descemet's Membrane Endothelial Keratoplasty with Deep Convolutional Neural Networks.

Purpose: We developed a method to automatically locate and quantify graft detachment after Descemet's membrane endothelial keratoplasty (DMEK) in anterior segment optical coherence tomography (AS-OCT) scans. Methods: A total of 1280 AS-OCT B-scans were annotated by a DMEK expert. Using the annotations, a deep learning pipeline was developed to localize scleral spur, center the AS-OCT B-scans and segment the detached graft sections. Detachment segmentation model performance was evaluated per B-scan by comparing (1) length of detachment and (2) horizontal projection of the detached sections with the expert annotations. Horizontal projections were used to construct graft detachment maps. All final evaluations were done on a test set that was set apart during training of the models. A second DMEK expert annotated the test set to determine interrater performance. Results: Mean scleral spur localization error was 0.155 mm, whereas the interrater difference was 0.090 mm. The estimated graft detachment lengths were in 69% of the cases within a 10-pixel (∼150 µm) difference from the ground truth (77% for the second DMEK expert). Dice scores for the horizontal projections of all B-scans with detachments were 0.896 and 0.880 for our model and the second DMEK expert, respectively. Conclusions: Our deep learning model can be used to automatically and instantly localize graft detachment in AS-OCT B-scans. Horizontal detachment projections can be determined with the same accuracy as a human DMEK expert, allowing for the construction of accurate graft detachment maps. Translational Relevance: Automated localization and quantification of graft detachment can support DMEK research and standardize clinical decision-making.

Deep anterior lamellar keratoplasty: dissection plane with viscoelastic and air can be different.

AIMS: To investigate and define the nature of big bubbles (BB) formed by injection of viscoelastic in deep anterior lamellar keratoplasty. METHODS: Intrastromal injections of 0.1 and 0.3 mL of sodium hyaluronate 1.2% and 0.6% were made into sclera-corneal discs (n = 32) at superficial (anterior-third), midstromal (middle-third) and deep (posterior-third) levels to simulate deep anterior lamellar keratoplasty. Postinjection optical coherence tomograms (OCT) were obtained with the needle in situ. The samples were sectioned and examined histologically. Twelve control samples were injected with air. RESULTS: With superficial injections (n=8) only intrastromal accumulation of viscoelastic was noted. With midstromal injections (n=10) intrastromal accumulation of viscoelastic (n=6) and intrastromal big bubbles (IBB) (n=4) with substantial and variable stromal tissue in the walls were noted. No type 1, type 2 or mixed BB were noted. With deep injections (n=14), type 1 BB (n=4), IBB (n=4) and mixed BB (n=6) were obtained.There was no difference in the results with the two different concentrations of viscoelastic used. With air injection (n=12), 10 type 1 and 1 type 2 BB and 1 mixed BB were obtained. No IBB was noted. CONCLUSIONS: BB obtained by injection of viscoelastic and air can be different. The former tends to occur at the site of injection, especially with midstromal injections, takes the form of tissue separation by stretch and tearing and does not cleave in a consistent plane like air. Surgeons should be aware of IBB created by viscodissection and not confuse it for a type1 BB. Intraoperative OCT should help identify IBB.

Scanning electron microscopy assessment of the Descemet membrane interface during DMEK graft preparation.

We set out to determine microscopic characteristics of the Descemet membrane interface during Descemet membrane endothelial keratoplasty (DMEK) graft preparation. Ten corneas were partially prepared, preserving half of the Descemet membrane attached to the stroma to enable visualisation of the Descemet-stroma interface. This tissue was prepared for viewing with a scanning electron microscope. The Descemet-stroma interface was categorised into three regions: centre, mid-periphery and periphery. We classified adhesions in these regions as either minor thread-like adhesions or major bridge-like adhesions with stromal detachments. We found a region-specific differentiation of the Descemet-stroma morphology. The presence of minor (P = 0,0001) and major (P = 0,0001) adhesions at the explored regions of the Descemet-stroma interface were found to be statistically significant. Fibrotic linear adhesions were predominant in the centre and mid-periphery, whereas the larger bridge-like adhesions were found mainly in the periphery. In addition, we observed a positive correlation between the size of the adhesions and the presence of ruptures in the underlying stromal bed. Viewing of the Descemet-stroma interface with electron microscopy reveals morphological differences between the centre of a graft and its periphery. These findings are of potential clinical relevance in terms of developing a better understanding of tissue behaviour during graft preparation.

Changes in lipidomic profile of aqueous humour in Fuchs endothelial dystrophy.

PURPOSE: To identify and determine differences in lipid profile of aqueous humour (AH) in patients with Fuchs endothelial corneal dystrophy (FECD). METHODS: Lipidomic profile of eight AH samples of FECD patients and 10 control samples was analysed. Patients with previous history of anterior segment surgery, anterior segment pathology or intraocular injections were excluded. Topical ocular medications within the last 6 months were reported. Aqueous humour (AH) was obtained during the first step of Descemet membrane endothelial keratoplasty in FECD patients and during refractive lensectomy in the control group. Lipidomic ultra-performance liquid chromatography mass spectrometry was used to perform an optimal profiling of glycerolipids, sterol lipids, sphingolipids and glycerophospholipids. Metabolite extraction was accomplished by fractionating the samples into pools of species with similar physicochemical properties. RESULTS: The levels of 27 of 110 lipids change significantly in the AH of FECD eyes when compared to control samples. The concentration of most diacylglycerophosphocholines and 1-ether, 2-acylglycerophosphocholines increases in the AH of FECD eyes when compared to healthy controls. In addition, eight sphingomyelins and up to two long-chain highly unsaturated cholesteryl esters present higher levels in FECD samples when compared to controls. CONCLUSION: The lipid composition of AH in FECD patients differs from that of healthy subjects. Those changes may reflect oxidative stress-related changes in the lipid metabolism of the corneal endothelial cells in FECD.

Changes in the Lipidomic Profile of Aqueous Humor in Open-Angle Glaucoma.

PURPOSE: To identify and determine differences in lipid profiles of aqueous humor (AH) in patients with open-angle glaucoma (OAG). MATERIALS AND METHODS: The lipidomic profile of 10 samples of AH of patients with OAG and 10 controls was analyzed. Patients with a history of anterior segment surgery, anterior segment pathology, or intraocular injections were excluded. Topical ocular medications within the last 6 months were reported. AH was obtained during the first step of nonperforating deep sclerotomy in OAG patients and during refractive lensectomy in controls. Lipidomic ultra-performance liquid chromatography mass spectrometry was used to perform an optimal profiling of glycerolipids, sterol lipids, sphingolipids, and glycerophospholipids. Metabolite extraction was accomplished by fractionating the samples into pools of species with similar physicochemical properties. RESULTS: The levels of 37 of 110 lipids changed in OAG when compared with controls samples. The concentration of most diacylglycerophosphocholines and 1-ether, 2-acylglycerophosphocholines increases in OAG when compared with healthy controls. In addition, 14 sphingomyelins increased significantly, up to 2.75-fold, in OAG. 5 cholesteryl esters are also present at higher levels in OAG when compared with controls. CONCLUSIONS: The lipid composition of AH in OAG patients shows differences when compared with healthy individuals. Changes in lipid synthesis may relate to oxidative stress metabolic response in OAG and may play an important role in the pathophysiology of the disease.

Changes in Surface Tension of Aqueous Humor in Anterior Segment Ocular Pathologies.

The aim of this study was to identify and determine differences in surface tension (ST) of aqueous humor (AH) in patients with cataract, glaucoma and Fuchs endothelial dystrophy (FED). Two hundred and two samples of AH were analyzed (control n = 22; cataract n = 56; glaucoma n = 81; and n = FED 43). Patients with previous history of anterior segment surgery, anterior segment pathology or intraocular injections were excluded from the study. Different types of glaucoma were identified, cataracts were graded using total phaco time data during surgery and clinical severity of FED was assessed by clinical examination. Around 150 microliters AH were obtained during the first step of a surgical procedure, lensectomy, phacoemulsification, nonpenetrating deep sclerotomy (NPDE) and Descemet membrane endothelial keratoplasty (DMEK). A pendant drop-based optical goniometer OCA-15 (Dataphysics, Filderstadt, Germany) was used to measure surface tension. Mean ST was 65.74 ± 3.76 mN/m, 63.59 ± 5.50 mN/m, 64.35 ± 6.99 mN/m, and 60.89 ± 3.73 mN/m in control, cataract, glaucoma and FED patients respectively. Statistically significant differences between FED and control group were found (p < 0.001). Lens condition, cataract maturity, age, and gender did not show influence in ST. ST of AH is significantly decreased in FED patients independently from age and lens condition. These findings may aid to the understanding of the physiopathology of the disease.

Changes in color vision and contrast sensitivity after descemet membrane endothelial keratoplasty for fuchs endothelial dystrophy.

PURPOSE: The aim of this study is to evaluate contrast sensitivity, color vision, and subjective patient satisfaction after Descemet membrane endothelial keratoplasty (DMEK) in patients with bilateral Fuchs endothelial dystrophy (FED). METHODS: From a group of 500 DMEK surgeries performed in our center, patients with a history of bilateral FED and unilateral DMEK were identified. A total of 29 patients were included in the study and divided into 2 groups: phakic (n = 12) and pseudophakic unilateral DMEK (n = 17) and their contralateral, untreated FED-affected eye. In addition, a control group of 10 healthy eyes of 10 patients was included. Pelli-Robson contrast sensitivity and Farnsworth-Munsell 100 hue color vision tests were performed. Subjective optical quality was graded with a questionnaire. RESULTS: Compared with untreated FED-affected eyes, best spectacle-corrected visual acuity was higher after DMEK in phakic and pseudophakic eyes (P = 0.030 and P < 0.001, respectively); a similar result was obtained for contrast sensitivity (P < 0.001 and P < 0.001, respectively). Color vision did not differ between untreated FED-affected and DMEK-operated eyes in the phakic group (P = 0.802) and the pseudophakic group (P = 0.227). Subjective optical quality was better in DMEK-operated eyes than in untreated FED-affected eyes in the phakic group (P < 0.001) and in the pseudophakic group (P < 0.001). CONCLUSIONS: In FED, DMEK may not only be effective for obtaining a higher visual acuity but particularly improving the contrast sensitivity may also lead to better subjective optical performance. Although frequently mentioned spontaneously by patients, an objective change in color vision could not be substantiated. Hence, quantifying contrast sensitivity before surgery may aid in the decision for surgery, and in the evaluation of surgical outcome.

Potential causes of incomplete visual rehabilitation at 6 months postoperative after descemet membrane endothelial keratoplasty.

PURPOSE: To determine the various causes of unexpected incomplete visual rehabilitation at 6 months postoperative after Descemet membrane endothelial keratoplasty (DMEK). DESIGN: Retrospective study of prospectively collected data at a tertiary referral center. METHODS: From a larger group of 400 consecutive DMEK surgeries, the last 200 consecutive eyes were reviewed for visual discomfort despite a best-corrected visual acuity (BCVA) of ≥20/25 (≥0.8) or unexpected subnormal BCVA (≤20/28; ≤0.7) at 6 months after DMEK. Biomicroscopy, funduscopy, Pentacam imaging, noncontact specular microscopy, anterior segment optical coherence tomography, and surgical videos were used to determine the causes of incomplete visual rehabilitation. RESULTS: A total of 69 eyes out of 178 eyes that were included in the analysis (38.8%) presented with incomplete visual rehabilitation after DMEK, further categorized as "primarily patient-related" in 40 of 178 (22.5%), "primarily graft-related" in 21 of 178 (11.8%), and a combination of "patient-/graft-related" in 8 of 178 cases (4.5%). Unrecognized pre-existing ocular pathology and/or posterior segment disease in 19 of 178 eyes (10.7%), clinically significant corneal irregularities and/or central corneal scarring often secondary to long-standing preoperative corneal edema in 14 of 178 eyes (7.9%), or (partial) graft detachment in 20 of 178 eyes (11.2%) were the main causes of unexpected incomplete visual rehabilitation. Transient or persistent monocular ghost images or diplopia occurred in 10 of 178 eyes (5.6%), sometimes requiring contact lens fitting. CONCLUSIONS: In contrast to earlier endothelial keratoplasty techniques that may frequently be associated with undefined transplant-related subnormal visual outcomes, incomplete visual rehabilitation after DMEK may virtually always be explained by concomitant ocular pathology or evident graft failure.

Outcomes of phacoemulsification after Descemet membrane endothelial keratoplasty.

PURPOSE: To evaluate the feasibility and outcomes of phacoemulsification after Descemet membrane endothelial keratoplasty (DMEK) for Fuchs endothelial dystrophy and bullous keratopathy. SETTING: Tertiary referral center. DESIGN: Comparative case series. METHODS: The case notes of all phakic DMEK patients who subsequently had cataract surgery were reviewed, and data from a prospectively recorded database were analyzed. This included demographic details, visual acuity, corneal pachymetry, endothelial cell density (ECD), refractive outcomes, and complications. RESULTS: From a series of 106 consecutive phakic DMEK eyes, 5 eyes (4.7%) required phacoemulsification a mean of 9.2 months ± 3.7 (SD) (range 4 to 14 months) after the initial DMEK. All phacoemulsification procedures were uneventful, and no dislocations and/or detachments of the Descemet graft were observed. At 6 to 12 months, all eyes reached a corrected distance visual acuity of 20/30 (0.6) or better and were within ±0.50 diopter of the target refraction. Endothelial cell density decreased from a mean of 1535 ± 195 cells/mm(2) before phacoemulsification to 1158 ± 250 cells/mm(2) 6 to 12 months after phacoemulsification. No significant changes in pachymetry values were observed, and all corneas remained clear throughout the study. CONCLUSIONS: Phacoemulsification after DMEK can be performed with minimal risk for graft detachment. The postoperative refractive outcomes were predictable, and visual acuity is likely to improve; there was an acceptable decrease in ECD. FINANCIAL DISCLOSURE: Dr. Melles is a consultant to D.O.R.C. International BV/Dutch Ophthalmic USA. No author has a financial or proprietary interest in any material or method mentioned.