Endothelial Migration and Regeneration after Penetrating Trauma Injury in a Deep Anterior Lamellar Keratoplasty Graft: Case Presentation and Literature Overview.

Background: Traumatic injuries in eyes previously treated with Deep Anterior Lamellar Keratoplasty (DALK) can lead to ruptures in the Descemet Membrane (DM) and damage to the corneal endothelium, a crucial layer for maintaining corneal clarity. Due to cell cycle constraints, the human corneal endothelium cannot proliferate; instead, it compensates for injury through cell enlargement and migration from adjacent areas. Methods: This study examines a notable case of corneal endothelial cell migration following a penetrating eye injury in a patient previously treated with DALK for keratoconus, supplemented by a review of relevant literature to contextualize the regenerative response. Results: A 39-year-old male with a history of DALK suffered a traumatic eye injury, resulting in damage to the Descemet Membrane and loss of the crystalline lens. After primary repair and considerations for further surgery, the patient's cornea cleared remarkably, with an improved visual acuity. This demonstrates the DM's potential for self-repair through endothelial cell migration. Conclusions: The outcomes suggest that delaying corneal transplant surgery for up to 3 months following Descemet Membrane injury due to ocular trauma could be advantageous. Allowing time for natural healing processes might eliminate the need for further invasive surgeries, thereby improving patient recovery outcomes.

New forceps free injection technique for delivering descemet membrane endothelial keratoplasty preloaded endothelium-in grafts.

PURPOSE: To describe a new method for delivering DMEK grafts into the recipient's eye with endothelium inward configuration using a no-forceps injection technique. METHODS: We retrospectively review 11 patients that underwent DMEK surgery at our institution using a no-forceps injection technique. The graft was preloaded into an intraocular lens (IOL) cartridge and connected to an anterior chamber maintainer (ACM). A 5 ml non luer lock syringe was inserted into the other end of the ACM to create a one-flow system. The cartridge was inserted into the posterior end of an injector, and the graft was successfully delivered into the recipient's eye. RESULT: Twelve eyes of 11 patients were included. Mean follow-up was 9.16 ± 1.3 months. At baseline, mean best corrected visual acuity (BCVA) was 0.76 ± 0.13 logMAr and mean endothelial cell density (ECD) was 2619.00 ± 115.89 cells/mm2. At follow-up, BCVA significantly improved to 0.22 ± 0.05 logMAR (p = 0.003). Although we observed a significant reduction in ECD at follow-up (1688 ± 182.20, p = 0.002), our patients lost only 35.69 ± 6.36% of endothelial cells. CONCLUSION: Our technique can help surgeons safely deliver an endothelium-in graft into the recipient's eye. The method doesn't require the use of a forceps, minimizing the risk of endothelial cell loss or graft damage.

Preoperative surgeon evaluation of corneal endothelial status: the Viability Control of Human Endothelial Cells before Keratoplasty (V-CHECK) study protocol.

INTRODUCTION: The success of keratoplasty strongly depends on the health status of the transplanted endothelial cells. Donor corneal tissues are routinely screened for endothelial damage before shipment; however, surgical teams have currently no means of assessing the overall viability of corneal endothelium immediately prior to transplantation. The aim of this study is to validate a preoperative method of evaluating the endothelial health of donor corneal tissues, to assess the proportion of tissues deemed suitable for transplantation by the surgeons and to prospectively record the clinical outcomes of a cohort of patients undergoing keratoplasty in relation to preoperatively defined endothelial viability. METHODS AND ANALYSIS: In this multicentre cohort study, consecutive patients undergoing keratoplasty (perforating keratoplasty, Descemet stripping automated endothelial keratoplasty (DSAEK), ultra-thin DSAEK (UT-DSAEK) or Descemet membrane endothelial keratoplasty) will be enrolled and followed-up for 1 year. Before transplantation, the endothelial viability of the donor corneal tissue will be evaluated preoperatively through trypan blue staining and custom image analysis to estimate the overall percentage of trypan blue-positive areas (TBPAs), a proxy of endothelial damage. Functional and structural outcomes at the end of the follow-up will be correlated with preoperatively assessed TBPA values. ETHICS AND DISSEMINATION: The protocol will be reviewed by the ethical committees of participating centres, with the sponsor centre issuing the final definitive approval. The results will be disseminated on ClinicalTrials.gov, at national and international conferences, by partner patient groups and in open access, peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT05847387.

Managing Post-Keratoplasty Astigmatism: High-Tech vs. Low-Tech Imaging Techniques for Guiding Suture Manipulation.

Astigmatism is a visually significant condition that can develop after keratoplasty. The management of post-keratoplasty astigmatism can be performed both when transplant sutures are in place and when they have been removed. Fundamental for astigmatism management is its identification and characterization in terms of type, amount, and direction. Commonly, post-keratoplasty astigmatism is evaluated through corneal tomography or topo-aberrometry; however, many other techniques can be used in case these instruments are not readily available. Here, we describe several low-tech and high-tech techniques used for post-keratoplasty astigmatism detection in order to quickly understand if it contributes to low vision quality and to determine its characteristics. The management of post-keratoplasty astigmatism through suture manipulation is also described.

Deep Learning Using Preoperative AS-OCT Predicts Graft Detachment in DMEK.

Purpose: To evaluate a novel deep learning algorithm to distinguish between eyes that may or may not have a graft detachment based on pre-Descemet membrane endothelial keratoplasty (DMEK) anterior segment optical coherence tomography (AS-OCT) images. Methods: Retrospective cohort study. A multiple-instance learning artificial intelligence (MIL-AI) model using a ResNet-101 backbone was designed. AS-OCT images were split into training and testing sets. The MIL-AI model was trained and validated on the training set. Model performance and heatmaps were calculated from the testing set. Classification performance metrics included F1 score (harmonic mean of recall and precision), specificity, sensitivity, and area under curve (AUC). Finally, MIL-AI performance was compared to manual classification by an experienced ophthalmologist. Results: In total, 9466 images of 74 eyes (128 images per eye) were included in the study. Images from 50 eyes were used to train and validate the MIL-AI system, while the remaining 24 eyes were used as the test set to determine its performance and generate heatmaps for visualization. The performance metrics on the test set (95% confidence interval) were as follows: F1 score, 0.77 (0.57-0.91); precision, 0.67 (0.44-0.88); specificity, 0.45 (0.15-0.75); sensitivity, 0.92 (0.73-1.00); and AUC, 0.63 (0.52-0.86). MIL-AI performance was more sensitive (92% vs. 31%) but less specific (45% vs. 64%) than the ophthalmologist's performance. Conclusions: The MIL-AI predicts with high sensitivity the eyes that may have post-DMEK graft detachment requiring rebubbling. Larger-scale clinical trials are warranted to validate the model. Translational Relevance: MIL-AI models represent an opportunity for implementation in routine DMEK suitability screening.

Incidence and management of early postoperative complications in lamellar corneal transplantation.

PURPOSE: To provide a comprehensive review of the incidence, risk factors, and management of early complications after deep anterior lamellar keratoplasty (DALK), Descemet stripping automated keratoplasty (DSAEK), and Descemet membrane endothelial keratoplasty (DMEK). METHODS: A literature review of complications, that can occur from the time of the transplant up to 1 month after the transplant procedure, was conducted. Case reports and case series were included in the review. RESULTS: Complications in the earliest postoperative days following anterior and posterior lamellar keratoplasty have shown to affect graft survival. These complications include, but are not limited to, double anterior chamber, sclerokeratitis endothelial graft detachment, acute glaucoma, fluid misdirection syndrome, donor-transmitted and recurrent infection, and Uretts-Zavalia syndrome. CONCLUSION: It is essential for surgeons and clinicians to not only be aware of these complications but also know how to manage them to minimize their impact on long-term transplant survival and visual outcomes.

Assessment of Corneal Angiography Filling Patterns in Corneal Neovascularization.

The purpose of the paper is to describe vascular filling patterns in corneal neovascularization (CoNV) and evaluate the effect of corneal lesion location, CoNV surface area and multi-quadrant CoNV involvement on the filling pattern. It is a retrospective study of patients who were investigated for CoNV using fluorescein angiography (FA) or indocyanine green angiography (ICGA) between January 2010 and July 2020. Angiography images were graded and analyzed multiple independent corneal specialists. The corneal surface was divided into four quadrants and patient information was obtained through electronic records. A total of 133 eyes were analyzed. Corneal lesions were located on the peripheral (72%) or central (28%) cornea. Central lesions were associated with multi-quadrant CoNV more frequently than peripheral lesions (p = 0.15). CoNV located within the same quadrant of the corneal lesion was often first to fill (88.4%). In multi-quadrant CoNV, the physiological inferior-superior-nasal-temporal order of filling was usually respected (61.7%). Central lesions resulted in larger CoNV surface area than peripheral lesions (p = 0.09). In multi-quadrant CoNV, the largest area of neovascularization was also the first to fill in (peripheral lesion 74%, central lesion 65%). Fillings patterns in healthy corneas have previously been reported. Despite CoNV development, these patterns are usually respected. Several factors that may influence filling patterns have been identified, including corneal lesion location, CoNV surface area and aetiology of CoNV. Understanding filling patterns of neovascularization allows for the identification of areas at higher risk of developing CoNV, aiding in earlier detection and intervention of CoNV.

Thinning rate over 24 months in ultrathin DSAEK.

AIM: To describe the changes in corneal graft thickness following ultrathin Descemet's Stripping Automated Endothelial Keratoplasty (UT-DSAEK) comparing pre- and postoperative values over a 24-month period. METHODS: In this retrospective single-center case series, patients who received eye bank-prepared tissues for UT-DSAEK surgery were included. Preoperative and postoperative graft thickness measurements were determined in the eye bank and in clinic using anterior segment optical coherence tomography (AS-OCT) images. Graft thickness measurements and their percentage change between preoperative values and values at 1 day, 1 week and 1, 6, 12, 24 months were calculated. RESULTS: In total, 47 eyes of 47 patients with a mean age of 69 ± 11 years (29 males) were included. Twnty-three patients had Fuchs' endothelial dystrophy (49%) and the remaining 24 had pseudophakic bullous keratopathy (51%). In total, 29/47 eyes underwent UT-DSAEK alone (62%) and 18/47 received combined cataract surgery as a triple procedure (38%). Preoperative donor graft thickness was 92 ± 28 µm. Compared to preoperative values, where graft thickness increased to 194 ± 101.3 µm at 1 day, 151.1 ± 71.4 µm at 1 week, and 108.4 ± 52.5 µm at 1 month. Graft thickness continued to gradually decrease over time until 6 months (91.7 ± 33.6 µm), and then plateaued at 12 months (83.9 ± 25.0 µm), showing minimal changes at 2 years (101.4 ± 37.5 µm). CONCLUSION: Preoperative DSAEK graft thickness measurements as reported by the eye bank are a valid approximation of DSAEK graft thickness at 6 months after surgery and these measurements tend to stabilize over time up to 2 years after surgery.

Surgical goniolens for tag identification and removal in DMEK surgery.

INTRODUCTION: We describe a novel technique for identifying endothelial Descemet membrane (DM) tags remaining after descemetorhexis in patients undergoing Descemet membrane endothelial keratoplasty (DMEK) surgery. METHODS: A surgical goniolens is applied to the corneal surface after descemetorhexis in order to visualize the peripheral inner corneal layer at 360° and identify endothelial-DM tags. RESULTS: A detailed visualization of the peripheral inner corneal layer is possible using goniolens, without using any staining in the anterior chamber. CONCLUSION: The technique may be used to screen the posterior corneal surface for any retained endothelial-DM tags. It may to lower the risk of remaining tags and indirectly lower the incidence of DMEK graft detachment.

Update on Suture Techniques in Corneal Transplantation: A Systematic Review.

Effective suturing remains key to achieving successful outcomes in corneal surgery, especially anterior lamellar keratoplasty and full thickness transplantation. Limitations in the technique may result in complications such as wound leak, infection, or high astigmatism post corneal graft. By using a systematic approach, this study reviews articles and conducts content analysis based on update 2020 PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses criteria). The aim of this paper is to summarize the state of the art of corneal suturing techniques for every type of corneal transplant and patient age and also their outcomes regarding astigmatism and complications. Future developments for corneal transplantation will be also discussed. This is important because especially the young surgeon must have knowledge of the implications of every suture performed in order to achieve consistent and predictable post-operative outcomes and also be aware of all the possible complications.

Eye bank versus surgeon prepared DMEK tissues: influence on adhesion and re-bubbling rate.

AIM: To investigate the difference in adhesion and rebubbling rate between eye bank and surgeon prepared Descemet membrane endothelial keratoplasty (DMEK) tissues. METHODS: Laboratory and clinical retrospective comparative interventional case series. Research corneal tissues were obtained for laboratory investigation. The clinical study involved patients with endothelial dysfunction who underwent DMEK surgery and tamponade with air. Tissues were stripped using a standard DMEK stripping technique (SCUBA) and shipped as prestripped or loaded in a 2.2 intra-ocular lens cartridge with endothelium facing inwards (preloaded) before transporting from the eye bank to the surgeon. For surgeon prepared tissues, all the grafts were stripped in the theatre and transplanted or stripped in the laboratory and tested immediately. Adhesion force and elastic modulus were measured in the centre and mid-periphery in a laboratory ex vivo investigation using atomic force microscopy, while rebubbling rates were recorded in the clinical study. RESULTS: There was no difference in endothelial cell viability between surgeon or eye bank prepared tissue. Surgeon-stripped DMEK grafts in the laboratory investigation showed significantly higher elastic modulus and adhesion force compared to prestripped and preloaded tissues (p<0.0001). In the clinical data, rebubbling rates of 48%, 40% and 15% were observed in preloaded, prestripped and surgeon-stripped DMEK grafts, respectively. Rebubbling rates were significantly associated with combined cataract surgery (p=0.009) and with time from harvesting the graft to the surgery (p=0.02). CONCLUSIONS: Decreased adhesion forces and elastic modulus in eye bank prepared tissues may contribute to increased rebubbling rates.

Cost analysis of eye bank versus surgeon prepared endothelial grafts.

BACKGROUND: Selective lamellar corneal transplantation (keratoplasty) has overtaken full thickness penetrating keratoplasty as the graft choice for endothelial failure. Even more recently eye bank prepared tissues are becoming increasing popular as a way to reduce the risks of tissue loss and stress during endothelial keratoplasty preparation in the surgical theatre. This study compares costs between surgeon and eye bank prepared tissues for Descemet's stripping automated endothelial keratoplasty (DSAEK) and Descemet's membrane endothelial keratoplasty (DMEK). METHODS: Retrospective study conducted at the Royal Liverpool University Hospital including endothelial keratoplasties with a minimum of 6 months follow-up time. Cost analysis included surgical expenses, tissue acquisition fees, cost of patient's ward admission and out-patient expenses, including cost of re-bubbling procedures, costs of visits, anterior segment imaging and optometrist visits within the first 6 months follow-up. RESULTS: Ninety-eight eyes of 98 patients were included in the study of which 42 underwent DSAEK surgery and 56 DMEK surgery. Cost analysis of surgical expenses in the DSAEK group showed a significant difference between using surgeon prepared and eye bank prepared tissue (£3866 ± 296 and £4389 ± 360, respectively; p < 0.01) and the same was found in the DMEK group (£3682 ± 167 and £4162 ± 167 for surgeon prepared and eye bank prepared tissues, respectively; p < 0.01). Cost of out-patient visits did not differ significantly in either group. CONCLUSIONS: At the Royal Liverpool University Hospital, eye bank prepared tissues had higher surgical expenses compared to those prepared by the surgeon, while the post-operative care expenses were similar between the two groups.

Tips, Tricks, and Guides in Descemet Membrane Endothelial Keratoplasty Learning Curve.

Lamellar keratoplasty is fast becoming the most popular form of corneal transplantation. The adoption of Descemet membrane endothelial keratoplasty (DMEK) in the management of Fuchs endothelial dystrophy and pseudophakic bullous keratopathy is partly responsible for this shift in the paradigm of management of corneal pathology. The learning curve of DMEK, however, has been proven to be much steeper than previous endothelial keratoplasty procedures. To ease the procedure, experts have proposed multiple innovative techniques from tissue preparation to graft unfolding to aid the more novice surgeon. Here, we collate and share tips and tricks from our collective experiences to support the learning curve and outcomes in DMEK for both the novice and more experienced corneal transplant surgeons.

Rebubbling rate in preloaded versus surgeon prepared DSAEK.

PURPOSE: To compare the clinical outcomes of eye bank preloaded Descemet stripping automated endothelial keratoplasty (DSAEK) grafts and surgeon prepared. METHODS: In this retrospective study, the data were obtained from two groups (a) surgeon cut DSAEK where tissue was prepared by the surgeon immediately before surgery, and (b) preloaded DSAEK tissue shipped to the surgeon after preparation by the eye bank. Standard DSAEK preparations using Moria microkeratome with single pass method were performed. For the tissues prepared by the eye banks, they were preloaded in an iGlide device and shipped in transport media. Standard DSAEK surgery using bimanual pull-through technique was performed for all the grafts. Air was used as a tamponade. Main outcome measures included best corrected visual acuity (BCVA) and rebubbling rate. RESULT: Out of 107 eyes of 101 patients that underwent DSAEK surgery, 33 tissues were prepared by the surgeon (sc-DSAEK), while 74 were prepared by the eye bank (pl-DSAEK). sc-DSAEK showed a rebubbling rate of 9.1%, compared to the 16.2% for the preloaded DSAEK (p = 0.11). There was no statistical difference in postoperative BCVA between the two groups. Logistic regression analysis showed no association between detachment rate and cataract surgery, graft preparation method, graft diameter and reason for graft. CONCLUSION: Preloaded grafts have similar rebubbling rate and visual acuity achieved compared with surgeon prepared grafts.

Impact of COVID-19 on keratoconus patients waiting for corneal cross linking.

PURPOSE: Royal College of Ophthalmologist recent guidance recommended delaying cross-linking services during the COVID-19 pandemic. This study investigates the effects of such delays in the delivery of cross-linking services in patients with keratoconus progression. METHODS: Retrospective observational study of 46 patients with keratoconus progression, whose cross-linking was delayed due to the COVID-19 pandemic. Demographic and clinical details were obtained from assessments on the day of listing, and subsequent review on the day of the procedure. Topographic indices included keratometry of the posterior and anterior corneal surface, maximum keratometry (Kmax), thinnest corneal thickness, ABCD progression and progression based on standard criteria recommendations (1.5 D Kmax & 20 microns thinning). RESULTS: A total of 46 eyes were analysed with an average time between being listed for CXL and having the procedure done was 182 ± 65 days. The delay due to COVID-19 was of 3 months. In this time period they had a significant worsening of all keratometric indices and lost almost one line of visual acuity (0.19 ± 0.19 to 0.26 ± 0.18 LogMAR, p: 0.03). Thirty two eyes (70%) demonstrated progression in accordance with the ABCD progression criteria, while 18 eyes (39%) showed either an increase in Kmax of more than 1.5D or a thinning in corneal thickness of at least 20 µm. CONCLUSIONS: The treatment delay for the keratoconus patients caused further progression and vision worsening. We recommend that corneal collagen crosslinking needs to be considered as a high priority intervention.

Influence of Corneal Visualization Scheimpflug Technology Tonometry on Intraocular Pressure.

Purpose: To investigate the effect of Corneal Visualization Scheimpflug Technology tonometry (CST) on intraocular pressure (IOP). Design: Cohort study. Participants: Patients with and without primary open-angle glaucoma (POAG) were included. Methods: Intraocular pressure was measured using the Icare rebound tonometer (ICRT; Icare Finland Oy) and the biomechanically corrected IOP (bIOP) using the CST. Intraocular pressure was measured at baseline with ICRT, followed by a CST measurement in one eye with the fellow eye acting as a control. Icare measurements were repeated at 10 seconds and 1, 2, 4, 8, 15, 30, and 60 minutes in both eyes. The ratio of test eye IOP to fellow eye IOP was used to control for intrasubject variation. Main Outcome Measures: Intraocular pressure change following Corneal Visualization Scheimflug Technology tonometry. Results: Forty participants (mean age, 54.09 ± 20.08 years) were included comprising 20 patients with POAG and 20 patients with no ocular abnormalities other than cataract. Mean central corneal thickness was similar in those without POAG (547.4 ± 55.05 µm) and with POAG (520.22 ± 37.59 µm; P = 0.14). No significant change was found in IOP measured with the ICRT in the fellow eye versus the 1-hour period in either the healthy (P = 0.87) or POAG (P = 0.92) group. Significant changes were found in IOP after CST measurement for both healthy (P < 0.01) and glaucomatous (P < 0.01) eyes. After the CST measurement, the IOP reduced continuously from a mean of 13.75 mmHg to 10.84 mmHg at 4 minutes for healthy eyes and from 13.28 mmHg to 11.11 mmHg at 8 minutes for glaucomatous eyes before approaching (83% for healthy eyes and 92% POAG eyes) the pre-CST measurement at 1 hour. Conclusions: Corneal Visualization Scheimpflug Technology tonometry causes a significant reduction in IOP in both glaucomatous and healthy eyes that lasts for at least 1 hour afterward.