[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.

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.

Hybrid bio-nanoporous peptide loaded-polymer platforms with anticancer and antibacterial activities.

In this study, hybrid bio-nanoporous peptides loaded onto poly(N-isopropylacrylamide-co-butylacrylate) (pNIPAM-co-BA) coatings were designed and obtained via matrix-assisted pulsed laser evaporation (MAPLE) technique. The incorporation of cationic peptides magainin (MG) and melittin (Mel) and their combination was tailored to target synergistic anticancer and antibacterial activities with low toxicity on normal mammalian cells. Atomic force microscopy, scanning electron microscopy, X-ray photoelectron spectroscopy, Fourier transform infrared spectroscopy as well as contact angle and surface energy measurements revealed the successful and functional incorporation of both the peptides within porous polymeric nanolayers as well as surface modifications (i.e. variation in the pore size diameter, surface roughness, and wettability) after Mel, MG or Mel-MG incorporation compared to pNIPAM-co-BA. In vitro testing revealed the impairment of biofilm formation on all the hybrid coatings while testing with S. aureus, E. coli and P. aeruginosa. Moreover, MG was shown to modulate the effect of Mel in the combined Mel-MG extract formulation released via pNIPAM-platforms, thus significantly reducing cancer cell proliferation through apoptosis/necrosis as revealed by flow cytometry analysis performed in vitro on HEK293T, A375, B16F1 and B16F10 cells. To the best of our knowledge, Mel-MG combination entrapped in the pNIPAM-co-BA copolymer has not yet been reported as a new promising candidate with anticancer and antibacterial properties for improved utility in the biomedical field. Mel-MG incorporation compared to pNIPAM-co-BA in in vitro testing revealed the impairment of biofilm formation in all the hybrid formulations.

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.

Prediction of compound-target interaction using several artificial intelligence algorithms and comparison with a consensus-based strategy.

For understanding a chemical compound's mechanism of action and its side effects, as well as for drug discovery, it is crucial to predict its possible protein targets. This study examines 15 developed target-centric models (TCM) employing different molecular descriptions and machine learning algorithms. They were contrasted with 17 third-party models implemented as web tools (WTCM). In both sets of models, consensus strategies were implemented as potential improvement over individual predictions. The findings indicate that TCM reach f1-score values greater than 0.8. Comparing both approaches, the best TCM achieves values of 0.75, 0.61, 0.25 and 0.38 for true positive/negative rates (TPR, TNR) and false negative/positive rates (FNR, FPR); outperforming the best WTCM. Moreover, the consensus strategy proves to have the most relevant results in the top 20 % of target profiles. TCM consensus reach TPR and FNR values of 0.98 and 0; while on WTCM reach values of 0.75 and 0.24. The implemented computational tool with the TCM and their consensus strategy at: https://bioquimio.udla.edu.ec/tidentification01/ . Scientific Contribution: We compare and discuss the performances of 17 public compound-target interaction prediction models and 15 new constructions. We also explore a compound-target interaction prioritization strategy using a consensus approach, and we analyzed the challenging involved in interactions modeling.

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.

MATEO: intermolecular α-amidoalkylation theoretical enantioselectivity optimization. Online tool for selection and design of chiral catalysts and products.

The enantioselective Brønsted acid-catalyzed α-amidoalkylation reaction is a useful procedure is for the production of new drugs and natural products. In this context, Chiral Phosphoric Acid (CPA) catalysts are versatile catalysts for this type of reactions. The selection and design of new CPA catalysts for different enantioselective reactions has a dual interest because new CPA catalysts (tools) and chiral drugs or materials (products) can be obtained. However, this process is difficult and time consuming if approached from an experimental trial and error perspective. In this work, an Heuristic Perturbation-Theory and Machine Learning (HPTML) algorithm was used to seek a predictive model for CPA catalysts performance in terms of enantioselectivity in α-amidoalkylation reactions with R2 = 0.96 overall for training and validation series. It involved a Monte Carlo sampling of > 100,000 pairs of query and reference reactions. In addition, the computational and experimental investigation of a new set of intermolecular α-amidoalkylation reactions using BINOL-derived N-triflylphosphoramides as CPA catalysts is reported as a case of study. The model was implemented in a web server called MATEO: InterMolecular Amidoalkylation Theoretical Enantioselectivity Optimization, available online at: https://cptmltool.rnasa-imedir.com/CPTMLTools-Web/mateo . This new user-friendly online computational tool would enable sustainable optimization of reaction conditions that could lead to the design of new CPA catalysts along with new organic synthesis products.

Long-term choroidal thickness changes based on the subtype of macular neovascularization in neovascular age-related macular degeneration (5-year follow-up).

PURPOSE: To evaluate the long-term choroidal thickness changes in combination with other morphological and functional outcomes during anti-vascular endothelial growth factor (VEGF) treatment for neovascular age-related macular degeneration (nAMD) based on the subtype of macular neovascularization (MNV): MNV-1 (within the subretinal pigment epithelium space) and MNV-2 (within the subretinal space). METHODS: This retrospective study included 58 eyes from 53 patients with naïve nAMD who received anti-VEGF therapy over a 60-month period. All eyes were treated initially with intravitreal bevacizumab following Pro re nata regimen. Main outcome measures included the following: subfoveal choroidal thickness (SFCT), best corrected visual acuity (BCVA), central macular thickness (CMT), development of subfoveal geographic atrophy (GA), and the number of injections. RESULTS: Thirty-four eyes had MNV-1 (group 1) and 24 eyes had MNV-2 (group 2). SFCT in group 1 vs group 2 was (210 ± 45 µm vs 191 ± 52 µm, p = 0.01) before treatment and (170 ± 47 µm vs 179 ± 48 µm, p = 0.24) after 60 months. BCVA (log MAR) in group 1 vs group 2 was (0.57 ± 0.18 vs 0.53 ± 0.22, p = 0.47) before treatment and (0.59 ± 0.23 vs 0.69 ± 0.16, p = 0.04) after 60 months. CMT in group 1 vs group 2 was (398 ± 154 µm vs 382 ± 103 µm, p = 0.86) before treatment and (297 ± 68 µm vs 283 ± 67 µm, p = 0.14) after 60 months. The number of injections per eye over a period of 60 months was significantly higher in group 1 (34.9 ± 11 vs 29.0 ± 14, p = 0.04). The proportion of eyes with subfoveal GA after 60 months was significantly higher in group 2 (13 eyes, 54%) than in group 1 (9 eyes, 25%) (p = 0.03). CONCLUSION: Over the full 60 months of anti-VEGF treatment, eyes with MNV-1 showed a greater reduction in choroidal thickness, better visual acuity, and less development of subfoveal geographic atrophy compared with eyes with MNV-2. The significantly thicker choroid in eyes with MNV type 1 at baseline seems to have a positive impact on long-term outcomes.

Chronic renal failure as predictive factor for acute elevation of systolic blood pressure after fluorescein angiography in patients with retinal diseases.

Purpose: To investigate the influence of fluorescein angiography (FA) on blood pressure (BP) in patients with retinal diseases, and analyze the predictive factors for acute elevation of systolic BP after FA. Design: and Methods: A prospective study was conducted with 636 patients undergoing FA between April 2021 and October 2021. BP and pulse were measured in each patient before and 20 min after FA. The baseline characteristics of patients who developed an acute elevation in systolic BP (>10 mmHg) were compared with those of the remaining patients to detect factors that may predict this acute elevation. Results: Overall, mean systolic BP changed from 142 ± 17 mmHg to 140 ± 20 mmHg after 20 min (p = 0.1). Mean diastolic BP changed from 79 ± 15 mmHg to 78 ± 13 mmHg after 20 min (p = 0.45). Mean pulse rate changed from 73 ± 14 bpm to 70 ± 12 bpm after 20 min (p = 0.001). 103 patients (16 %) had acute elevation of systolic BP (>10 mmHg). Mean systolic BP changed from 143 ± 17 mmHg to 162 ± 19 mmHg after 20 min in this group (p = 0.001). Patients in this group were significantly older compared to the rest (73 ± 12 vs 67 ± 15, p = 0.001). The rate of chronic renal failure was significantly higher in this group compared to the rest of the patients (42/7.8 % vs 15/14.6 %, p = 0.01). Conclusions: This study demonstrated that fluorescein angiography is a relatively safe procedure with regards to blood pressure changes. However, chronic renal failure could be considered as predictive factor for acute elevation of systolic blood pressure after this procedure.

The Effect of Glaucoma Treatment on Aniridia-Associated Keratopathy (AAK) - A Report from the Homburg Register for Congenital Aniridia.

BACKGROUND: Congenital aniridia is a severe malformation of almost all eye segments. Aniridia-associated keratopathy (AAK) and secondary glaucoma, which occur in more than 50% of affected individuals, are typically progressive and pose a high risk of blindness for patients with congenital aniridia. Our aim was to investigate the effect of glaucoma treatment on AAK in patients of the Homburg Aniridia Center. METHODS: Our retrospective monocentric study included patients who underwent a comprehensive ophthalmological examination at the Homburg Aniridia Center between June 2003 and January 2022. RESULTS: There were 556 eyes of 286 subjects (20.1 ± 20.1 years; 45.5% males) included. In 307 (55.2%) eyes of 163 subjects (27.5 ± 16.3 years; 43.1% males), glaucoma was present at the time of examination. The mean intraocular pressure in the glaucoma group was 19.0 mmHg (± 8.0), while in the non-glaucoma group, it was 14.1 mmHg (± 3.6) (p < 0.001). In the glaucoma group, 68 patients used antiglaucomatous topical monotherapy, 51 patients used 2 agents, 41 patients used 3 agents, 7 patients used quadruple therapy, and 140 did not use topical therapy (e.g., after pressure-lowering surgery, pain-free end-stage glaucoma, or incompliance). Patients were classified according to the following stages of AAK: Stage 0 (96 eyes [17.2%], no keratopathy), Stage 1 (178 eyes [32.0%]), Stage 2 (107 eyes [19.2%]), Stage 3 (67 eyes [12.0%]), Stage 4 (62 eyes [11.1%]), Stage 5 (45 eyes [8.0%]). The mean stage of AAK was 1.4 (1.2 - 1.5) in the group without eye drops, 1.9 (1.5 - 2.2) in the group with monotherapy, 1.8 (1.5 - 2.1) in the group with 2 drugs, 1.9 (1.5 - 2.2) in the group with 3 drugs, 3.4 (2.3 - 4.6) in the group with 4 drugs, and 3.3 (3.1 - 3.6) after antiglaucomatous surgery. The stage of AAK was significantly positively correlated with the number of pressure-lowering eye drops (p < 0.05) and prior pressure-lowering surgery (p < 0.05). Prostaglandin analogues were not correlated with a higher AAK stage compared to the other drug groups. CONCLUSIONS: At the Homburg Aniridia Center, patients using topical antiglaucomatous quadruple therapy or who had previously undergone antiglaucomatous surgery had by far the highest AAK stage. The different drug groups had no influence on the AAK stage.

Vision-Related Quality of Life among Patients with Different Types of Age-Related Macular Degeneration.

BACKGROUND: This study aimed to assess the vision-related quality of life (VRQol) of patients with age-related macular degeneration (AMD) and to evaluate VRQol according to different types of AMD. METHODS: In this small-scale, single-center, prospective investigation, patients with AMD and subjects without any signs of macular disease were asked to complete the NEI-VFQ-39. A total of 159 subjects were included and grouped according to the type of AMD as follows: 40 patients with dry AMD in both eyes (DD), 40 patients with exudative AMD in one eye (DE), 41 patients with exudative AMD in both eyes (EE), and 38 subjects without any signs of macular disease, as a control group (CG). RESULTS: The average age of the participants was 76 ± 7 years, and 44% were male. Most participants were retired (22.4%), and 75% of patients were initially diagnosed by their ophthalmologist. All the AMD groups had significantly worse overall VRQol than the CG. For general vision, near vision, mental health, and role difficulties, all the AMD groups had significantly lower scores than the CG. For distance vision, color vision, peripheral vision, driving difficulties, dependency, and social functioning, only patients in the EE and DE groups had significantly worse scores than the CG. The type of retinal fluid in patients with exudative AMD had no effect on overall VRQol; however, we found that the presence of pigment epithelial detachment could be associated with more role difficulties, such as completing work or working long hours. CONCLUSION: All types of AMD had a negative effect on vision-related quality of life. This effect was significantly more pronounced in patients with exudative AMD in at least one eye. However, the type of retinal fluid in patients with exudative AMD had no influence on their overall vision-related quality of life.

A Cross-sectional Analysis of 556 Eyes Entering the Homburg Aniridia Centre.

PURPOSE: Congenital aniridia is a severe malformation of almost all eye segments. In addition, endocrinological, metabolic, and central nervous systems diseases may be present. In order to develop better treatment options for this rare disease, an aniridia center must be established. The purpose of this work is to summarize ophthalmic findings of aniridia subjects examined at the Department of Ophthalmology, Saarland University Medical Center in Homburg. METHODS: Our retrospective single-center study included patients who underwent a comprehensive ophthalmic examination through the head of the KiOLoN ("Kinderophthalmologie", Orthoptics, Low Vision and Neuroophthalmology) Unit of the department between June 2003 and January 2022. Data at the first examination time point have been included. RESULTS: Of 286 subjects, 556 eyes of (20.1 ± 20.1 years; 45.5% males) were included. There was nystagmus in 518 (93.7%) eyes, and strabismus in 327 (58.8%) eyes. There were 436 (78.4%) eyes with age-appropriate axial length, 104 (18.7%) eyes with microphthalmos, and 13 (2.3%) eyes with buphthalmos. There was iris malformation with atypical coloboma in 34 eyes (6.1%), more than 6 clock hours of iris remnants in 61 eyes (10.9%), less than 6 clock hours of iris remnants in 96 eyes (17.2%), and complete aniridia in 320 (57.5%) eyes. The patients were graded according to the following aniridia-associated keratopathy (AAK) stages: Stage 0 (96 eyes [17.2%], no keratopathy), Stage 1 (178 eyes [32.0%]), Stage 2 (107 eyes [19.2%]), Stage 3 (67 eyes [12.0%]), Stage 4 (62 eyes [11.1%]), Stage 5 (45 eyes [8.0%]). There was secondary glaucoma in 307 (55.5%), macular hypoplasia in 395 (71.4%), and congenital optic nerve head pathology in 223 (40.3%) eyes. The iris malformation type was significantly positively correlated with AAK stage, lens properties, presence of glaucoma, congenital macular, and optic nerve head properties (p < 0.001 for all), while complete aniridia showed the most complications. CONCLUSIONS: At the Homburg Aniridia Center, the most common ophthalmic signs in congenital aniridia were AAK, iris malformation, cataract, and macular hypoplasia. The iris malformation type may indicate future expression of AAK, cataract, and glaucoma development and it is correlated with a congenital optic nerve head and macular pathology. Our registry will support further detailed longitudinal analysis of ophthalmic and systemic diseases of aniridia subjects during long-term follow-up.

Incidence and treatment approach of intraocular pressure elevation after various types of local steroids for retinal diseases.

PURPOSE: For the treatment of macular edema, in addition to the use of antivascular endothelial growth factors, steroids are also used intravitreally and sub-Tenon. Side effects include among others cataract formation and elevation of intraocular pressure (IOP). The aim of this retrospective study was to elicit the IOP elevation after administration of various steroidal medication, the time of onset, and the efficacy of the administered IOP-lowering therapies. METHODS: We included 428 eyes with a postoperative (n = 136), diabetic (n = 148), uveitic macular edema (n = 61), and macular edema after retinal vein occlusion (n = 83). These patients were treated with one or more diverse steroidal agents once or multiple times. These drugs included: triamcinolone acetonide (TMC) as intravitreal injection (TMC IVI) or sub-Tenon (TMC ST), as well as dexamethasone (DXM) and fluocinolone acetonide (FA) intravitreally. An increase of IOP of ≥ 25 mmHg was designated as pathological. A steroid response in anamnesis, the time of onset of IOP rise from the first administration, and the therapy administered were documented. RESULTS: Of 428 eyes, 168 eyes (39.3%) had IOP elevation up to a mean of 29.7 (SD ± 5.6) mmHg, which occurred at a median of 5.5 months. Steroids most frequently leading to rise of IOP included DXM (39.1% of all eyes receiving that drug), TMC IVI (47.6%), TMC ST combined with DXM (51.5%), DXM with FA (56.8%), and TMC IVI with DXM (57.4%). A Kaplan-Meier analysis and the Log Rank test showed a significant difference (p < 0.001). IOP rise was treated as follows: 119 conservatively (70.8%), and 21 surgically (12.5%, cyclophotocoagulation 8.3%, filtering surgery 1.8%, in 4 the steroidal drug implant was removed 2.4%), and 28 eyes received no therapy (16.7%). Sufficient IOP regulation was achieved in 82 eyes (68.9%) with topical therapy. In 37 eyes (31.1%) with persistently elevated intraocular pressure, topical therapy had to be continued over the follow-up of 20 ± 7 months. CONCLUSIONS: IOP increases after any type of steroid application are not rare. Results of our study let us suspect that especially therapy with intravitreal dexamethasone, either as a monotherapy or in combination with another steroid, tends to increase IOP more than other steroids. Regular IOP checks are necessary after each steroid administration, with possible initiation of long-term conservative and/or surgical therapy if necessary.

NPC1 plays a role in the trafficking of specific cargo to melanosomes.

Niemann-Pick type C1 (NPC1) protein is a multimembrane spanning protein of the lysosome limiting membrane that facilitates intracellular cholesterol and sphingolipid transport. Loss-of-function mutations in the NPC1 protein cause Niemann-Pick disease type C1, a lysosomal storage disorder characterized by the accumulation of cholesterol and sphingolipids within lysosomes. To investigate whether the NPC1 protein could also play a role in the maturation of the endolysosomal pathway, here, we have investigated its role in a lysosome-related organelle, the melanosome. Using a NPC1-KO melanoma cell model, we found that the cellular phenotype of Niemann-Pick disease type C1 is associated with a decreased pigmentation accompanied by low expression of the melanogenic enzyme tyrosinase. We propose that the defective processing and localization of tyrosinase, occurring in the absence of NPC1, is a major determinant of the pigmentation impairment in NPC1-KO cells. Along with tyrosinase, two other pigmentation genes, tyrosinase-related protein 1 and Dopachrome-tautomerase have lower protein levels in NPC1 deficient cells. In contrast with the decrease in pigmentation-related protein expression, we also found a significant intracellular accumulation of mature PMEL17, the structural protein of melanosomes. As opposed to the normal dendritic localization of melanosomes, the disruption of melanosome matrix generation in NPC1 deficient cells causes an accumulation of immature melanosomes adjacent to the plasma membrane. Together with the melanosomal localization of NPC1 in WT cells, these findings suggest that NPC1 is directly involved in tyrosinase transport from the trans-Golgi network to melanosomes and melanosome maturation, indicating a novel function for NPC1.

Methionine oxidation selectively enhances T cell reactivity against a melanoma antigen.

The impact of the peptide amino acids side-chain modifications on the immunological recognition has been scarcely explored. We investigate here the effect of methionine oxidation on the antigenicity of the melanoma immunodominant peptide 369-YMDGTMSQV-377 (YMD). Using CD8+ T cell activation assays, we found that the antigenicity of the sulfoxide form is higher when compared to the YMD peptide. This is consistent with free energy computations performed on HLA-A∗02:01/YMD/TCR complex showing that this is lowered upon oxidation, paired with a steep increase in order at atomic level. Oxidized YMD forms were identified at the melanoma cell surface by LC-MS/MS analysis. These results demonstrate that methionine oxidation in the antigenic peptides may generate altered peptide ligands with increased antigenicity, and that this oxidation may occur in vivo, opening up the possibility that high-affinity CD8+ T cells might be naturally primed in the course of melanoma progression, as a result of immunosurveillance.

The Biomechanical E-Staging: In Vivo Biomechanics in Keratoconus. / Das biomechanische E-Staging: In-vivo-Biomechanik beim Keratokonus.

Belin's ABCD keratoconus classification system allows keratoconus staging based on the criteria of anterior (A) and posterior (B) corneal curvature, thinnest corneal thickness (C), and best spectacle-corrected visual acuity (D). These parameters also provide a progression assessment, but do not take corneal biomechanics into account. The analysis of corneal biomechanics by the Corvis ST (Oculus, Wetzlar, Germany) allows for separation of healthy and keratoconus corneas, based on the Corvis Biomechanical Index (CBI) and the Tomographic Biomechanical Index (TBI). As Corvis ST measurements are highly reliable and are independent of keratoconus severity, a biomechanical parameter was developed for keratoconus corneas based on the linear term of the CBI. This provides biomechanical keratoconus staging. The Corvis Biomechanical Factor (CBiF) is the basis for the introduction of the biomechanical E-staging, which augments the ABCD classification to the ABCDE classification, thus including the cornerstone of corneal biomechanics. This article highlights strengths and limitations of the ABCDE classification. "Unilateral keratoconus" supposedly turns out to be mostly a snapshot of a highly asymmetric keratectasia. Regular astigmatism is sometimes an important differential diagnosis to keratectasia and may be difficult to differentiate from it. Furthermore, the use of the biomechanical E-staging in daily practice for progression assessment of keratoconus and after its treatment by corneal cross-linking or implantation of intracorneal ring segments will be demonstrated and discussed.

Factors Associated With SARS-CoV-2 Infection at a German Medical Congress During the Omicron Wave.

This cross-sectional study assesses factors associated with SARS-CoV-2 infection rates at the 122nd Annual Congress of the German Society of Ophthalmology in 2022, which was held in-person for the first time in 3 years, during the Omicron wave.

Culturing Limbal Epithelial Cells of Long-term Stored Corneal Donors (Organ Culture) In Vitro - A Stepwise Linear Regression Algorithm.

PURPOSE: To assess various potential factors on human limbal epithelial cell (LEC) outgrowth in vitro using corneal donor tissue following long-term storage (organ culture) and a stepwise linear regression algorithm. METHODS: Of 215 donors, 304 corneoscleral rings were used for our experiments. For digestion of the limbal tissue and isolation of the limbal epithelial cells, the tissue pieces were incubated with 4.0 mg/mL collagenase A at 37 °C with 95% relative humidity and a 5% CO2 atmosphere overnight. Thereafter, limbal epithelial cells were separated from limbal keratocytes using a 20-µm CellTricks filter. The separated human LECs were cultured in keratinocyte serum-free medium medium, 1% penicillin/streptomycin (P/S), 0.02% epidermal growth factor (EGF), and 0.3% bovine pituitary extract (BPE). The potential effect of donor age (covariate), postmortem time (covariate), medium time (covariate), size of the used corneoscleral ring (360°, 270°180°, 120°, 90°, less than 90°) (covariate), endothelial cell density (ECD) (covariate), gender (factor), number of culture medium changes during organ culture (factor), and origin of the donor (donating institution and storing institution, factor) on the limbal epithelial cell outgrowth was analyzed with a stepwise linear regression algorithm. RESULTS: The rate of successful human LEC outgrowth was 37.5%. From the stepwise linear regression algorithm, we found out that the relevant influencing parameters on the LEC growth were intercept (p < 0.001), donor age (p = 0.002), number of culture medium changes during organ culture (p < 0.001), total medium time (p = 0.181), and size of the used corneoscleral ring (p = 0.007), as well as medium time × size of the corneoscleral ring (p = 0.007). CONCLUSIONS: The success of LEC outgrowth increases with lower donor age, lower number of organ culture medium changes during storage, shorter medium time in organ culture, and smaller corneoscleral ring size. Our stepwise linear regression algorithm may help us in optimizing LEC cultures in vitro.

Different Course of Immune Reactions and Endothelial Cell Loss after Penetrating Low-Risk Keratoplasty and Descemet Membrane Endothelial Keratoplasty for Fuchs Endothelial Dystrophy. / Unterschiedlicher Verlauf von Immunreaktionen und Endothelzellverlust nach perforierender Low-Risk-Keratoplastik und Descemet Membrane Endothelial Keratoplasty bei Fuchs-Endotheldystrophie.

BACKGROUND: The aim of this study was to compare the incidence of immune reactions and endothelial cell loss after penetrating keratoplasty (PKP) vs. Descemet membrane endothelial keratoplasty (DMEK) in patients with Fuchs endothelial dystrophy (FED). PATIENTS AND METHODS: In the present retrospective study, a total of 962 surgeries (225 excimer laser PKP and 727 DMEK) of 700 patients performed between 28.06.2007 and 27.08.2020 in the Department of Ophthalmology at Saarland University Medical Center UKS were statistically evaluated. On the one hand, the prevalence and the temporal course of the immune reactions that occurred were analysed using the Kaplan-Meier method, as well as the effect of the immune reactions on the endothelial cells and corneal thickness. Secondly, endothelial cell density, pleomorphism, and polymegethism of the endothelial cells were evaluated for the time points U1 = preoperative, U2 = 6 weeks postoperative, U3 = 6 to 9 months postoperative, U4 = 1 to 2 years postoperative, and U5 = 5 years postoperative. In addition, statistical tests were carried out for differences between the two types of surgery and in the longitudinal course. RESULTS: A total of 54 immune reactions occurred during the observed period, whereby the probability of such a reaction was significantly greater in the PKP group with 8.9% than in the DMEK group with 4.5% (p = 0.011). The comparison of the two Kaplan-Meier curves also showed a significant difference between the two surgical techniques in the log-rank test (p = 0.012). The endothelial cell loss due to the immune reaction was only significant in PKP (p = 0.003). For all surgical procedures, endothelial cell density decreased significantly with time in both surgical techniques (p < 0.0001 in each case), but more strongly with DMEK than with PKP (p < 0.0001). Furthermore, this cell density was significantly higher with PKP than with DMEK for the whole observation time (p < 0.0001). Polymegethism decreased significantly in the DMEK group (p < 0.0001). Pleomorphism was significantly higher, on average, in DMEK than in PKP (p < 0.0001). CONCLUSION: The prognosis of DMEK in patients with FED seems to be more favourable after immune reactions than that of PKP, as not only were immune reactions less frequent, but they were also milder. However, endothelial cell density was significantly higher in the PKP group during the entire follow-up.