Review for special issue: Corneal lamellar surgery: Present outcomes and future perspectives.

Since the establishment of the first eye bank in the 1940s, their role has evolved to face new challenges. With the recent development of lamellar keratoplasties, eye banks play an even bigger role in the selection and preparation of donor tissues. The increasing number of keratoplasty techniques and the high demand for "ready-to-use" tissues are challenging eye banks to improve and develop new preparation techniques. Besides necessary examinations, new approaches of tissue analysis in eye banks allow a better/optimized selection of corneal tissues. These new challenges in tissue preservation, preparation, and selection are propelling eye banks into a new era of modern eye banking.

Rose Bengal Photodynamic Therapy (RB-PDT) Modulates the Inflammatory Response in LPS-Stimulated Human Corneal Fibroblasts By Influencing NF-κB and p38 MAPK Signaling Pathways.

PURPOSE: To investigate the effect of rose bengal photodynamic therapy on lipopolysaccharide-induced inflammation in human corneal fibroblasts. Furthermore, to analyze potential involvement of the mitogen-activated protein kinase and nuclear factor kappa B signaling pathways in this process. METHODS: Human corneal fibroblast cultures underwent 0-2.0 µg/mL lipopolysaccharide treatment, and 24 h later rose bengal photodynamic therapy (0.001% RB, 565 nm wavelength illumination, 0.17 J/cm2 fluence). Interleukin-6, interleukin-8, intercellular adhesion molecule-1, interferon regulatory factor-3, interferon α2, and interferon ß1 gene expressions were determined by quantitative PCR. Interleukin-6, interleukin-8, and C-C motif chemokine ligand-4 concentrations in the cell culture supernatant were measured by enzyme-linked immunosorbent assays and intercellular adhesion molecule-1 protein level in human corneal fibroblasts by western blot. In addition, the nuclear factor kappa B and mitogen-activated protein kinase signaling pathways were investigated by quantitative PCR and phosphorylation of nuclear factor kappa B p65 and p38 mitogen-activated protein kinase by western blot. RESULTS: Rose bengal photodynamic therapy in 2.0 µg/mL lipopolysaccharide-stimulated human corneal fibroblasts triggered interleukin-6 and interleukin-8 mRNA (p < .0001) and interleukin-6 protein increase (p < .0001), and downregulated intercellular adhesion molecule-1 expression (p < .001). C-C motif chemokine ligand-4, interferon regulatory factor-3, interferon α2, and interferon ß1 expressions remained unchanged (p ≥ .2). Rose bengal photodynamic therapy increased IκB kinase subunit beta, nuclear factor kappa B p65, extracellular signal-regulated kinases-2, c-Jun amino terminal kinase, and p38 transcription (p ≤ .01), and triggered nuclear factor kappa B p65 and p38 mitogen-activated protein kinase phosphorylation (p ≤ .04) in lipopolysaccharide treated human corneal fibroblasts. CONCLUSION: Rose bengal photodynamic therapy of lipopolysaccharide-stimulated human corneal fibroblasts can modify the inflammatory response by inducing interleukin-6 and interleukin-8 expression, and decreasing intercellular adhesion molecule-1 production. C-C motif chemokine ligand-4, interferon regulatory factor-3, and interferon α and ß expressions are not affected by rose bengal photodynamic therapy in these cells. The underlying mechanisms may be associated with nuclear factor kappa B and p38 mitogen-activated protein kinase pathway activation.

[Impact of the ratio between graft and host corneal size on immune rejection, re-bubbling rate and postoperative endothelial cell loss in 457 eyes after Descemet membrane endothelial keratoplasty (DMEK)]. / Einfluss des Verhältnisses von Transplantatgröße zu Hornhautgröße auf Immunreaktion, Re-Bubbling-Rate und postoperativen Endothelzellverlust bei 457 Augen nach Descemet-Membrane-Endothelial-Keratoplastik (DMEK).

BACKGROUND: The aim of this study was to assess the impact of the ratio between the graft and host corneal size (RGH) on postoperative complications, such as immune reactions, re-bubbling rate and endothelial cell loss (ECL) after Descemet membrane endothelial keratoplasty (DMEK). PATIENTS AND METHODS: Retrospectively, 457 patient eyes were included which had undergone surgery between 2016 and 2019 in the Department of Ophthalmology, Saarland University Medical Center in Homburg/Saar using DMEK or triple DMEK, diagnosed as Fuchs' endothelial dystrophy (n = 431), pseudophakic bullous keratopathy (n = 9) and others (n = 17). The follow-up period extended until the end of 2020. Main outcome measures included immune reaction (IR), re-bubbling rate and the postoperative endothelial cell loss (ECL) at 6 weeks, 6 months and 12 months and whether these measures depended on the RGH. RESULTS: The RGH in this study ranged from 0.35 to 0.62 (0.46 ± 0.04). There were 33 (7.2%) postoperative IRs (DMEK n = 25; triple DMEK n = 8). The average RGH without IR (0.46 ± 0.04) was significantly (p = 0.038) smaller than in the group with IR (0.47 ± 0.05). Re-bubbling was necessary in 159 of 457 (34.8%) patient eyes. The RGH in patient eyes with re-bubbling (0.47 ± 0.04) was significantly (p = 0.014) higher than that in eyes without re-bubbling (0.45 ± 0.04). The mean preoperative endothelial cell count (ECD) was 2603 ± 251 cells/mm2 (min: 2161, max: 3500 cells/mm2). It was shown that a larger RGH had no positive influence on endothelial cell loss (r = 0.001; p = 0.974). CONCLUSION: Our results suggest that a larger graft diameter compared to host corneal size is associated with an increased rate of immune reactions and a higher re-bubbling rate after DMEK. Otherwise, a larger RGH had no positive influence on endothelial cell loss after DMEK. Accordingly, the graft size for DMEK should not be unnecessarily large, especially in eyes with Fuchs' endothelial dystrophy.

Simulator-Based Versus Traditional Training of Fundus Biomicroscopy for Medical Students: A Prospective Randomized Trial.

INTRODUCTION: Simulation training is an important component of medical education. In former studies, diagnostic simulation training for direct and indirect funduscopy was already proven to be an effective training method. In this prospective controlled trial, we investigated the effect of simulator-based fundus biomicroscopy training. METHODS: After completing a 1-week ophthalmology clerkship, medical students at Saarland University Medical Center (n = 30) were block-randomized into two groups: The traditional group received supervised training examining the fundus of classmates using a slit lamp; the simulator group was trained using the Slit Lamp Simulator. All participants had to pass an Objective Structured Clinical Examination (OSCE); two masked ophthalmological faculty trainers graded the students' skills when examining patient's fundus using a slit lamp. A subjective assessment form and post-assessment surveys were obtained. Data were described using median (interquartile range [IQR]). RESULTS: Twenty-five students (n = 14 in the simulator group, n = 11 in the traditional group) (n = 11) were eligible for statistical analysis. Interrater reliability was verified as significant for the overall score as well as for all subtasks (≤ 0.002) except subtask 1 (p = 0.12). The overall performance of medical students in the fundus biomicroscopy OSCE was statistically ranked significantly higher in the simulator group (27.0 [5.25]/28.0 [3.0] vs. 20.0 [7.5]/16.0 [10.0]) by both observers with an interrater reliability of IRR < 0.001 and a significance level of p = 0.003 for observer 1 and p < 0.001 for observer 2. For all subtasks, the scores given to students trained using the simulator were consistently higher than those given to students trained traditionally. The students' post-assessment forms confirmed these results. Students could learn the practical backgrounds of fundus biomicroscopy (p = 0.04), the identification (p < 0.001), and localization (p < 0.001) of pathologies significantly better with the simulator. CONCLUSIONS: Traditional supervised methods are well complemented by simulation training. Our data indicate that the simulator helps with first patient contacts and enhances students' capacity to examine the fundus biomicroscopically.

Descemet Membrane Endothelial Keratoplasty (DMEK) Anesthesia Analysis.

PURPOSE: Comparison of safety and clinical results of Descemet membrane endothelial keratoplasty (DMEK) in topical, peribulbar, or general anesthesia. METHODS: Retrospective, post hoc matched study of 346 patients who received DMEK surgery with different types of anesthesia (n = 54 topical, n = 137 peribulbar, n = 155 general anesthesia). Outcome criteria were intraoperative complications, endothelial cell count (ECC), central corneal thickness (CCT) and graft rejection rate, rebubbling rate, and visual acuity (VA). Mean follow-up time was 9.4 ± 2.8 months. RESULTS: The group with topical anesthesia showed intraoperative difficulties such as vitreous pressure (p = 0.01) and difficult graft unfolding (p = 0.4), possibly leading to a higher rebubbling rate (p = 0.03) and therefore graft failure (p = 0.39). However, rebubbling and graft failure occurred more often when the graft preparation was more difficult (p = 0.2, p = 0.13, respectively), which was independent of anesthesia. All three groups achieved comparable functional results regarding VA, ECC, and CCT after 6 months. CONCLUSION: DMEK under topical anesthesia is feasible and shows comparable final visual outcomes but should be limited to selected cooperative patients and performed by experienced surgeons due to the potential for increased intraoperative challenges.

First-Year Real-Life Experience with Intravitreal Faricimab for Refractory Neovascular Age-Related Macular Degeneration.

Background: To evaluate the outcomes of intravitreal faricimab (IVF) for refractory neovascular age-related macular degeneration (nAMD) and investigate the impact of baseline optical coherence tomography, biomarkers for total IVF injections are needed. Methods: A retrospective analysis of 33 eyes of patients who completed one year (52 W) of treatment with IVF. The eyes received four IVF injections (6 mg/0.05 mL) as the upload phase. Thereafter, the treatment interval was extended to 8 or 12 weeks if disease activity was not recorded. The outcome measures included best-corrected visual acuity (BCVA), central macular thickness (CMT), subfoveal choroidal thickness (SFCT), and retinal fluid distribution. Results: A total of 33 eyes were included. CMT decreased significantly at 52 W (p < 0.01). BCVA and SFCT did not change significantly at 52 W (p > 0.05). The number of eyes with subretinal fluid decreased significantly at 52 W (p < 0.01). Complete fluid resolution was achieved in 20 eyes (60%). The total number of injections was significantly negatively correlated with the presence of hyperreflective dots at baseline (HRDs, p < 0.01) and SFCT at baseline (p < 0.01). Conclusions: IVF led to a significant reduction in CMT with stabilization of BCVA. The total number of injections was lower in eyes with HRDs and increased SFCT at baseline. This might provide clues regarding response to IVF for future studies.

Evaluation of dynamic corneal response parameters and the biomechanical E-staging after Intacs® SK implantation in keratoconus.

PURPOSE: This retrospective longitudinal study evaluated the biomechanical E-staging in KC corneas before and after intracorneal ring segment (ICRS) implantation (Intacs® SK, Addition Technology, Illinois, United States). METHODS: Biomechanical E-staging for ectatic corneal diseases was applied retrospectively on 49 KC corneas of 41 patients who underwent ICRS implantation. The main outcome parameters included the Corvis Biomechanical Factor (CBiF, the linearized Corvis Biomechanical Index and the biomechanical parameters included), the resulting biomechanical E-staging, the stress-strain index, thinnest corneal thickness (TCT), maximal anterior keratometry (Kmax), and the anterior radius of curvature (ARC). They were evaluated at 1.9 ± 1.1 months preoperatively and postoperatively after 2.8 ± 0.7, 5.8 ± 1.0, and 10.6 ± 2.3 months. RESULTS: The CBiF decreased (4.9 ± 0.5 | 4.7 ± 0.5, P = 0.0013), and the E-staging increased significantly (2.8 ± 0.8 | 3.1 ± 0.9, P = 0.0012, paired t-test) from preoperatively to the first postoperative follow-up. The difference remained significant after 6 months; however, there was no more difference after 11 months. TCT was stable, whereas Kmax and ARC significantly decreased after ICRS implantation (TCT: 464 ± 49, 470 ± 51, 467 ± 38, 461 ± 48; Kmax: 56.3 ± 4.5, 54.7 ± 4.5, 54.2 ± 4.8, 54.1 ± 4.3; ARC: 51.5 ± 3.4, 48.3 ± 3.8, 48.6 ± 3.0, 48.6 ± 3.2 preoperatively and 3, 6, and 11 months postoperatively, respectively). Besides Kmax and ARC, Ambrósio's relational thickness to the horizontal profile (ARTh) was the only parameter that was significantly lower than preoperatively at any follow-up (P ≤ 0.0024, Wilcoxon matched-pairs test). CONCLUSION: Intacs® SK implantation results in an increasing biomechanical E-staging in the first postoperative months with stabilization near preoperative values after 1 year. Significantly lower ARTh values at any follow-up document the ICRS effect and contribute to a slightly higher postoperative biomechanical E-staging value.

Short-term outcomes of intravitreal faricimab for refractory neovascular age-related macular degeneration.

PURPOSE: To assess the short-term outcomes of intravitreal faricimab (IVF) for previously treated refractory neovascular age-related macular degeneration (nAMD) in a real-world setting. METHODS: A retrospective monocentric study including 44 eyes treated with an upload of 4 × monthly intravitreal injections (IVI) of faricimab 6 mg/0.05 mL and followed for 4 weeks after last IVI (16 W). Patients were switched to IVF after treatment with at least three other anti-vascular endothelial growth factors (anti-VEGF). Main outcome measures included best-corrected visual acuity (BCVA), central macular thickness (CMT), subfoveal choroidal thickness (SFCT) and retinal fluid distribution. RESULTS: 44 eyes of 44 patients with previously treated refractory nAMD (63% males) were included. Mean age was 79 ± 7 years. The total number of previous anti-VEGF before switching to IVF was 32 ± 15 IVIs/eye. BCVA (logMAR) improved significantly from 0.65 ± 0.26 to 0.50 ± 0.23 at 16 W (p < 0.01). CMT (µm) decreased significantly from 422 ± 68 to 362 ± 47 at 16 W (p < 0.01). SFCT did not change significantly at 16 W (p = 0.06). The number of eyes with subretinal fluid (SRF) decreased significantly from 29 (65%) to 13 (29%) at 16 W (p = 0.001). There were no significant changes regarding the distribution of intraretinal fluid or pigment epithelial detachment (p > 0.05). A complete fluid resolution was achieved in 8 eyes (18%). No adverse events were noticed. CONCLUSION: In the short term, IVF led to a significant decrease in CMT as well as a significant improvement of BCVA and thus appears to be an effective treatment option for previously treated refractory nAMD without relevant adverse effects.

Analysis of Graft Detachments and Re-Bubblings After 450 Descemet Membrane Endothelial Keratoplasty Procedures.

PURPOSE: To objectify the indication for re-bubbling by analyzing graft detachments (GDs) after Descemet membrane endothelial keratoplasty. METHODS: In this retrospective monocentric observational study, re-bubbling cases of 450 Descemet membrane endothelial keratoplasties and the percentage of the residual gas filling (RGF) in the anterior chamber on the first postoperative day were collected. The number/location/extent of GDs and the corneal thickness above GDs were analyzed using anterior segment optical coherence tomography. RESULTS: From a total of 450 grafts, 384 (85.3%) had at least a minimal degree GD. One hundred twenty-two of 450 grafts (27.1%) underwent at least 1 re-bubbling. The mean RGF was significantly lower in eyes with GD (67.7 ± 12.6%) than in eyes without GD (74.2 ± 11.3%). GDs occurred most frequently in the inferotemporal quadrant (46.0%). GDs were significantly more likely to require a re-bubbling when the central parts of the graft were affected (94.0% vs. 35.7%). The number of detachments per graft was directly proportional to the re-bubbling rate. The GDs which required a re-bubbling were on average 56 µm higher and 461 µm wider than the untreated ones. The cornea above the GDs that needed a re-bubbling was significantly thicker than above the untreated GDs (mean 988 ± 102 µm vs. 951 ± 99 µm). CONCLUSIONS: The RGF seems to be a major influencing factor for graft attachment. The most susceptible location of the GD is inferotemporal. The main factors that need to be investigated to decide if a re-bubbling is required are the number of detachments per graft, their dimensions, whether the central portions of the graft are involved, and the corneal thickness above GDs.

PCR testing for herpesviruses in aqueous humor samples from patients with and without clinical corneal endothelial graft rejection.

To compare prevalence of positive PCR tests for herpesviruses between patients with and without a history of clinical corneal endothelial allograft rejection (AGR). Retrospective cross-sectional study with two-group comparison. A total of 307 aqueous humor (AH) samples from 235 Patients and 244 eyes who underwent penetrating keratoplasty or Descemet membrane endothelial keratoplasty or had a diagnostic AH aspiration due to clinical AGR between 2019 and 2023 were tested for DNA of herpes simplex virus (HSV), varicella-zoster virus (VZV), cytomegalovirus (CMV), and Epstein-Barr virus (EBV). PCR test results were compared between the two groups (with/without AGR). Another sub-analysis examined the results of patients without a history of herpetic keratitis. A total of 8% of eyes with clinical AGR (9/108) had a positive PCR result for one of the herpesviruses (HSV:3, CMV:3, EBV:2, VZV:1). All patients in the group without AGR had negative PCR results for all previous viruses (0/136). The difference was statistically significant (p < 0.001). The sub-analysis of eyes without a history of herpetic keratitis also revealed significantly more positive herpes PCR results (7/87) in eyes with AGR than in eyes without AGR (0/42, p = 0.005). Clinical AGR after keratoplasty shows a significant correlation to viral replication. Herpetic infection and AGR could occur simultaneously and act synergistically. Timely differentiation between active herpetic infection and/or AGR is pivotal for proper treatment and graft preservation.

UV light-mediated corneal crosslinking as (lymph)angioregressive pretreatment to promote graft survival after subsequent high-risk corneal transplantation (CrossCornealVision): protocol for a multicenter, randomized controlled trial.

BACKGROUND: Good vision highly depends on the transparency of the cornea, which is the "windscreen" of the eye. In fact, corneal blindness due to transparency loss is the second most common cause of blindness worldwide, and corneal transplantation is the main cure. Importantly, the cornea is normally avascular but can secondarily be invaded by pathological (blood and lymphatic) vessels due to severe inflammation, and the survival prognosis of a corneal graft mainly depends on the preoperative vascular condition of the recipient's cornea. Whereas transplants placed into avascular recipient beds enjoy long-term survival rates of > 90%, survival rates significantly decrease in pathologically pre-vascularized, so-called high-risk recipients, which account for around 10% of all performed transplants in Germany and > 75% in lower and middle-income countries worldwide. METHODS: This parallel-grouped, open-randomized, multicenter, prospective controlled exploratory investigator-initiated trial (IIT) intends to improve graft survival by preconditioning pathologically vascularized recipient corneas by (lymph)angioregressive treatment before high-risk corneal transplantation. For this purpose, corneal crosslinking (CXL) will be used, which has been shown to potently regress corneal blood and lymphatic vessels. Prior to transplantation, patients will be randomized into 2 groups: (1) CXL (intervention) or (2) no pretreatment (control). CXL will be repeated once if insufficient reduction of corneal neovascularization should be observed. All patients (both groups) will then undergo corneal transplantation. In the intervention group, remaining blood vessels will be additionally regressed using fine needle diathermy (on the day of transplantation). Afterwards, the incidence of graft rejection episodes will be evaluated for 24 months (primary endpoint). Overall graft survival, as well as regression of corneal vessels and/or recurrence, among other factors, will be analyzed (secondary endpoints). DISCUSSION: Based on preclinical and early pilot clinical evidence, we want to test the novel concept of temporary (lymph)angioregressive pretreatment of high-risk eyes by CXL to promote subsequent corneal graft survival. So far, there is no evidence-based approach to reliably improve graft survival in the high-risk corneal transplantation setting available in clinical routine. If successful, this approach will be the first to promote graft survival in high-risk transplants. It will significantly improve vision and quality of life in patients suffering from corneal blindness. TRIAL REGISTRATION: ClinicalTrials.gov NCT05870566. Registered on 22 May 2023.

Severe ulcerative keratopathy following implantation of an acellular porcine corneal stromal lenticule in a patient with keratoconus.

PURPOSE: To report a case of ulcerative keratopathy following implantation of acellular porcine corneal stroma (APCS) in a patient with keratoconus (KC). METHODS: A 58 year-old patient initially presented with an ulcerative keratopathy in the left eye. Previously, several corneal procedures (including radial keratotomy, laser-in-situ keratomileusis, crosslinking) were performed for KC. Eight months ago, an APCS lenticule (Xenia corneal implant, Gebauer Medizintechnik GmbH, Neuhausen, Germany) was implanted into a stromal pocket because of progressive keratectasia. Visual acuity was hand movement. Anterior segment optical coherence tomography showed a space between the APCS lenticule and the host stroma. Excimer laser-assisted penetrating keratoplasty (PKP, 8.0/8.1 mm) was performed in the left eye. The corneal explant was investigated by light and transmission electron microscopy. RESULTS: Best-corrected visual acuity was 20/40 six weeks after PKP. Light microscopy demonstrated a stromal ulceration down to the APCS lenticule. No stromal cells could be found within the APCS lenticule eight months after implantation. The APCS lenticule did not show a green stain of the collagens with Masson-Goldner staining and exhibited a strong Periodic acid-Schiff positive reaction. Electron microscopy of the APCS lenticule revealed cross-linked collagen lamellae without cellular components. Close to the interface, corneal collagen lamellae of the host cornea were disorganized. Few vital keratocytes were present on the surface of the lenticule and appeared to cause mechanical disruption of the host stroma along the lenticule-stroma interface. CONCLUSION: APCS implantation may lead to severe complications such as ulcerative keratopathy in otherwise uncomplicated KC corneas. In such cases, excimer laser-assisted PKP or Deep Anterior Lamellar Keratoplasty are the methods of choice to restore visual acuity.

Postmortem sympathomimetic iris excitability.

BACKGROUND: A reliable estimation of time since death can be important for the law enforcement authorities. The compound method encompassing supravital reactions such as the chemical excitability of the iris can be used to further narrow intervals estimated by temperature-based methods. Postmortem iris excitability was mostly assessed by parasympatholytic or parasympathomimetic substances. Little is known regarding sympathomimetic agents. The present study aims to describe the postmortem iris excitability using the sympathomimetic drug phenylephrine. METHODS: Cadavers were included after body donors gave written informed consent during lifetime. Exclusion criteria were known eye disease, or a postmortem interval exceeding 26 hours. A pupillometer with a minimum measurement range of 0.5 mm was used to determine the horizontal pupil diameter before and 20 minutes after the application of phenylephrine. Increase in pupil diameter was labeled as positive reaction, unchanged pupil diameter was labeled as negative reaction, and decrease in pupil diameter was labeled as paradox reaction. RESULTS: 30 eyes from 16 cadavers (median age = 80.0; 9 males, 7 females) were examined. Initial pupil size was in median 3.5 mm (interquartile range [IQR]: 3.0-4.5 mm) and progressed to 4.0 mm (IQR: 3.5-5.0 mm) 20 minutes after drug instillation. The achieved pupil diameter difference comprised in median 0.5 mm (IQR: 0.0-1.0 mm). A positive reaction was observed in 21 cases. Negative reactions were observed in 5 cases and paradox reactions in 4 cases. Overall, there was a statistically significant difference in diameter between the initial and the reactive pupil (P = 0.0002). CONCLUSION: Although relatively rarely used, sympathomimetic drugs seem to be eligible for chemical postmortem iris excitability. Currently, assessment of postmortem iris excitability usually only involves parasympatholytic and parasympathomimetic agents. The findings of the present study give a hint that the application of a third agent with a sympathomimetic mechanism of action could provide additional information. Further studies assessing such a triple approach in the compound method in comparison with the current gold standard for estimation of time since death are mandatory to ensure reliable results.

Long-Term Follow-Up of Pediatric Excimer Laser-Assisted Penetrating Keratoplasty for Congenital Stromal Corneal Dystrophy.

PURPOSE: The purpose of this study was to highlight characteristic clinical and microscopic findings and report the long-term follow-up of pediatric excimer laser-assisted penetrating keratoplasty (excimer-PKP) for congenital stromal corneal dystrophy (CSCD). METHODS: A 2-year-old Greek child presented with CSCD at our department. Clinical examination showed bilateral flake-like whitish corneal opacities affecting the entire corneal stroma up to the limbus. Genetic testing identified a mutation of the decorin gene (c.962delA). The variant was not present in the parents and represented a de novo mutation. The uncorrected visual acuity was 20/100 in both eyes. Excimer-PKP (8.0/8.1 mm) was performed on the right eye at the age of 2.5 years and on the left eye at the age of 3 years. Postoperatively, alternating occlusion treatment was performed. RESULTS: The light microscopic examination demonstrated a disorganized extracellular matrix of the corneal stroma characterized by a prominent irregular arrangement of stromal collagen lamellae with large interlamellar clefts containing ground substance, highlighted by periodic acid-Schiff- and Alcian blue-positive reaction detecting acid mucopolysaccharides. Electron microscopy showed disorganization and caliber variation of collagen lamellae and thin filaments within an electron-lucent ground substance. The postoperative course was unremarkable. Both grafts remained completely clear 14 years postoperatively. Corneal tomography showed moderate regular astigmatism with normal corneal thickness. The corrected distance visual acuity was 20/25 in both eyes. CONCLUSIONS: Excimer-PKP for CSCD might be associated with excellent long-term results and a good prognosis, particularly when the primary surgery is performed at a very young age. However, this requires close postoperative follow-up examinations by an experienced pediatric ophthalmologist to avoid severe amblyopia.

IC3D Classification of Corneal Dystrophies-Edition 3.

PURPOSE: The International Committee for the Classification of Corneal Dystrophies (IC3D) was created in 2005 to develop a new classification system integrating current information on phenotype, histopathology, and genetic analysis. This update is the third edition of the IC3D nomenclature. METHODS: Peer-reviewed publications from 2014 to 2023 were evaluated. The new information was used to update the anatomic classification and each of the 22 standardized templates including the level of evidence for being a corneal dystrophy [from category 1 (most evidence) to category 4 (least evidence)]. RESULTS: Epithelial recurrent erosion dystrophies now include epithelial recurrent erosion dystrophy, category 1 ( COL17A1 mutations, chromosome 10). Signs and symptoms are similar to Franceschetti corneal dystrophy, dystrophia Smolandiensis, and dystrophia Helsinglandica, category 4. Lisch epithelial corneal dystrophy, previously reported as X-linked, has been discovered to be autosomal dominant ( MCOLN1 mutations, chromosome 19). Classic lattice corneal dystrophy (LCD) results from TGFBI R124C mutation. The LCD variant group has over 80 dystrophies with non-R124C TGFBI mutations, amyloid deposition, and often similar phenotypes to classic LCD. We propose a new nomenclature for specific LCD pathogenic variants by appending the mutation using 1-letter amino acid abbreviations to LCD. Pre-Descemet corneal dystrophies include category 1, autosomal dominant, punctiform and polychromatic pre-Descemet corneal dystrophy (PPPCD) ( PRDX3 mutations, chromosome 10). Typically asymptomatic, it can be distinguished phenotypically from pre-Descemet corneal dystrophy, category 4. We include a corneal dystrophy management table. CONCLUSIONS: The IC3D third edition provides a current summary of corneal dystrophy information. The article is available online at https://corneasociety.org/publications/ic3d .

Altered Corneal Biomechanics According to the Biomechanical E-Staging in Pellucid Marginal Degeneration.

PURPOSE: The purpose of this study was to investigate corneal biomechanics in pellucid marginal degeneration (PMD) compared with healthy controls using Corvis ST (Oculus, Germany) by using the new biomechanical E-staging (based on the Corvis Biomechanical Factor, the linearized Corvis Biomechanical Index) together with tomographic parameters. METHODS: Corneal biomechanical and topographic data of 75 eyes of 75 patients with PMD and 75 eyes of 75 age-matched and sex-matched healthy controls were investigated. Topographic parameters (K1, K2, Kmax, central corneal thickness (CCT), and Belin/Ambrósio Deviation Index (BAD-D) were evaluated in dependence of and correlated with the biomechanically defined E-stages. Biomechanical parameters were also recorded for the 2 groups. RESULTS: Patients with PMD showed higher K2, Kmax, BAD-D, and Corvis Biomechanical Factor values and a lower CCT compared with healthy controls (P < 0.001). The E-stage was positively correlated with K1, K2, Kmax, BAD-D, and intraocular pressure difference and negatively correlated with CCT. Stage-dependent analysis revealed a significant increase in K1, K2, Kmax (P < 0.001), and BAD-D (P = 0.041) in stage E3 compared with E0 and a significant decrease in stage E2 in CCT (P = 0.009) compared with E0. CONCLUSIONS: This study showed that patients with PMD may have a reduced corneal stiffness compared with healthy controls which worsens with increasing E-stage. Significant changes in topographic parameters were observed at stage E2 for CCT and at stage E3 for K1, K2, Kmax, and BAD-D when compared with stage E0.

Impact of Pachychoroid and DRIL on the Treatment of Diabetic Macular Oedema with Intravitreal Bevacizumab.

PURPOSE: To evaluate the long-term outcome of intravitreal bevacizumab in eyes with diabetic macular oedema (DME) following a PRN (pro re nata) regimen. Additionally, we investigated the effect of the presence of disorganisation of the retinal inner layers (DRILs) and pachychoroid (PC) at baseline on clinical outcome. METHODS: This retrospective study included 112 naïve eyes with DME that were followed up for 2 years. All eyes were treated with six initial bevacizumab injections at monthly intervals and then received treatment according to a PRN regimen. In case of poor response to bevacizumab, therapy was switched to other agents. Main outcome measures included: best-corrected visual acuity (BCVA), central macular thickness (CMT), and number of intravitreal injections (IVI s). In addition, we examined the effect of the presence of DRILs and PC at baseline on clinical outcome. RESULTS: BVCA improved significantly and CMT decreased significantly during the first 2 years of treatment. The number of IVI s per eye was 11.1 ± 4.8 at the end of the second year. Treatment had to be switched to other agents in 47 eyes (42%). The timing of switching was 12.4 ± 6.1 months after a mean of 9.2 ± 3.3 IVI s. Patients with DRILs at baseline (29.5%) had significantly worse BCVA at all time points before and after treatment, although CMT was significantly lower before treatment and comparable to patients without DRILs during treatment. Patients with PC at baseline (35.7%) had no significant differences in BVCA and CMT at all time points compared with patients without PC. CONCLUSIONS: This study demonstrates statistically significant functional and anatomical improvement in patients with DME treated with intravitreal bevacizumab after 2 years. However, more than 40% of eyes required a switch in therapy. The presence of DRILs at baseline had a negative effect whereas the presence of PC at baseline had no effect on clinical outcome.

Descemet Membrane Endothelial Keratoplasty after failed penetrating keratoplasty- case series and review of the literature.

BACKGROUND: This study aims to evaluate visual outcome, central corneal thickness, and re-bubbling rate in a cohort with undersized sequential Descemet Membrane Endothelial Keratoplasty (DMEK) due to endothelial graft decompensation following primary penetrating keratoplasty (PK). METHODS: All patients who received a sequential DMEK (n = 16) or triple DMEK (n = 2) after failed primary PK between November 2020 and June 2022 were retrospectively evaluated. Analyzed parameters were corrected distance visual acuity (CDVA), central corneal thickness (CCT), re-bubbling rate and graft survival. RESULTS: 18 eyes of 18 patients were included. All patients underwent a DMEK with undersized graft after failed PK(s). Mean time between the last PK and DMEK was 102 ± 82 weeks. Mean follow-up time was 8.9 ± 4.6 months. CDVA increased significantly from 1.12 ± 0.60 logMAR preoperatively to 0.64 ± 0.49 logMAR 6 weeks postoperatively (p = 0.013). Mean CCT decreased significantly from 807 ± 224 µm before to 573 ± 151 µm 6 weeks after DMEK (p = 0.003). Re-bubbling was necessary in eight eyes (44.4%) after a median time of 7 days. The 12-month Kaplan Meier survival was 66.7%. CONCLUSION: In case of endothelial graft decompensation without stromal scars after primary PK, a DMEK can be performed for selected patients who had satisfying CDVA before the endothelial decompensation. Prior to DMEK indication, an AS-OCT should routinely be performed to circularly search for posterior steps at the PK graft margin, as well as shortly after DMEK to exclude a detachment of the endothelial graft. All patients should be informed about a higher re-bubbling rate in comparison to primary DMEK.

Calcium Electroporation versus Electrochemotherapy with Bleomycin in an In Vivo CAM-Based Uveal Melanoma Xenograft Model.

Despite recent advancements in the diagnosis and treatment of uveal melanoma (UM), its metastatic rate remains high and is accompanied by a highly dismal prognosis, constituting an unmet need for the development of novel adjuvant therapeutic strategies. We established an in vivo chick chorioallantoic membrane (CAM)-based UM xenograft model from UPMD2 and UPMM3 cell lines to examine its feasibility for the improvement of selection of drug candidates. The efficacy of calcium electroporation (CaEP) with 5 or 10 mM calcium chloride (Ca) and electrochemotherapy (ECT) with 1 or 2.5 µg/mL bleomycin in comparison to monotherapy with the tested drug or electroporation (EP) alone was investigated on the generated UM tumors. CaEP and ECT showed a similar reduction of proliferation and melanocytic expansion with a dose-dependent effect for bleomycin, whereas CaEP induced a significant increase of the apoptosis and a reduction of vascularization with varying sensitivity for the two xenograft types. Our in vivo results suggest that CaEP and ECT may facilitate the adequate local tumor control and contribute to the preservation of the bulbus, potentially opening new horizons in the adjuvant treatment of advanced UM.