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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., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: To present ocular clinical, histological, systemic, and genetic findings of a patient with familial lecithin-cholesterol acyltransferase (LCAT) deficiency caused by a novel genetic variant of the LCAT gene associated with secondary corneal amyloidosis., Methods: Case report., Results: A 74-year-old woman presented with decreased visual acuity (VA), sensitivity to light, and progressive whitening of both corneas for approximately 20 years. The patient had undergone penetrating keratoplasty (PKP) on the right eye 6 years ago. Ophthalmologic examination revealed decreased VA in both eyes (OD: 0.05, OS: 0.3), and even further reduced glare VA (OD: 0.05, OS: 0.1), diffuse whitish corneal opacity involving the total thickness of the corneal stroma without crystalline deposits, and a marked peripheral diffuse arcus. Systemic examination revealed severely reduced plasma high-density lipoprotein cholesterol levels, target cells in blood smear, and chronic normochromic anemia. Clinically, LCAT deficiency was the most likely diagnosis. Further genetic analysis confirmed the diagnosis. The patient is homozygous for the novel variant c.943T>C (p.Trp315Arg) in the LCAT gene. Histologic examination of the cornea removed during the first keratoplasty revealed amyloid deposits. The cornea removed at the second keratoplasty had small vacuoles in the anterior stroma, indicating recurrence of lipid deposition., Conclusions: LCAT deficiency is a rare genetic disorder that can cause corneal opacities because of lipid deposition in the cornea. Systemic manifestations may help in the differential diagnosis to other diseases associated with severe high-density lipoprotein cholesterol reduction. Genetic analysis is employed to confirm the diagnosis. Some mutations in the LCAT gene seem to be associated with secondary corneal amyloidosis. Further investigation of this association is warranted. A recurrence of corneal opacity after PKP seems to occur mainly in the anterior corneal stroma., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

The human microbiome emerges as a promising reservoir for diagnostic markers and therapeutics. Since host-associated microbiomes at various body sites differ and diseases do not occur in isolation, a comprehensive analysis strategy highlighting the full potential of microbiomes should include diverse specimen types and various diseases. To ensure robust data quality and comparability across specimen types and diseases, we employ standardized protocols to generate sequencing data from 1931 prospectively collected specimens, including from saliva, plaque, skin, throat, eye, and stool, with an average sequencing depth of 5.3 gigabases. Collected from 515 patients, these samples yield an average of 3.7 metagenomes per patient. Our results suggest significant microbial variations across diseases and specimen types, including unexpected anatomical sites. We identify 583 unexplored species-level genome bins (SGBs) of which 189 are significantly disease-associated. Of note, the existence of microbial resistance genes in one specimen was indicative of the same resistance genes in other specimens of the same patient. Annotated and previously undescribed SGBs collectively harbor 28,315 potential biosynthetic gene clusters (BGCs), with 1050 significant correlations to diseases. Our combinatorial approach identifies distinct SGBs and BGCs, emphasizing the value of pan-body pan-disease microbiomics as a source for diagnostic and therapeutic strategies., (© 2024. The Author(s).)

Background: Early therapeutic penetrating keratoplasty (TKP) for Acanthamoeba keratitis (AK) is thought to have a worse visual prognosis than the delayed optical penetrating keratoplasty (OKP) after successful conservative treatment of AK. This has led to a tendency to prolong conservative therapy and delay penetrating keratoplasty in patients with AK. This retrospective series presents the results of patients with AK that underwent early penetrating keratoplasty after reducing the corneal amoeba load through intensive conservative therapy, so-called " low load keratoplasty " (LLKP)., Patients and Methods: The medical records of our department were screened for patients with AK, confirmed by histological examination and/or PCR and/or in vivo confocal microscopy, which underwent ab LLKP and had a follow-up time of at least one year between 2009 and 2023. Demographic data, best corrected visual acuity (BCVA) and intraocular pressure at first and last visit, secondary glaucoma (SG), and recurrence and graft survival rates were assessed., Results: 28 eyes of 28 patients were included. The average time from initiation of therapy to penetrating keratoplasty (PKP) was 68 ± 113 days. The mean follow-up time after LLKP was 53 ± 42 months. BCVA (logMAR) improved from 1.9 ± 1 pre-operatively to 0.5 ± 0.6 at last visit ( p < 0.001). A total of 14% of patients were under medical therapy for SG at the last visit, and two of them underwent glaucoma surgery. The recurrence rate was 4%. The Kaplan-Meier graft survival rate of the first graft at four years was 70%. The second graft survival rate at four years was 87.5%., Conclusion: LLKP appears to achieve a good visual prognosis with an earlier visual and psychological habilitation, as well as low recurrence and SG rates. These results should encourage us to reconsider the optimal timing of PKP in therapy-resistant AK.

Purpose: To examine the in-vitro expression of matrix metalloproteinases (MMP) and tissue inhibitors of metalloproteinases (TIMP) in corneal stromal cells by distinguishing between fibroblasts and keratocytes of healthy and keratoconus (KC) corneas., Methods: Stromal cells were isolated from healthy and KC corneas (n = 8). A normal-glucose, serum-containing cell culture medium (NGSC-medium) was used for cultivation of healthy human corneal fibroblasts (HCFs) and KC human corneal fibroblasts (KC-HCFs). In order to obtain a keratocyte phenotype, the initial cultivation with NGSC-medium was changed to a low-glucose, serum-free cell culture medium for healthy (Keratocytes) and KC cells (KC-Keratocytes). Gene and protein expression of MMP-1, -2, -3, -7, -9 and TIMP-1, -2, -3 were measured by quantitative PCR and Enzyme-Linked Immunosorbent Assay (ELISA) from the cell culture supernatant., Results: KC-HCFs demonstrated a lower mRNA gene expression for MMP-2 compared to HCFs. In contrast to their respective fibroblast groups (either HCFs or KC-HCFs), Keratocytes showed a higher mRNA gene expression of TIMP-3, whereas TIMP-1 mRNA gene expression was lower in Keratocytes and KC-Keratocytes. Protein analysis of the cell culture supernatant revealed lower concentrations of MMP-1 in KC-HCFs compared to HCFs. Compared to Keratocytes, TIMP-1 concentrations was lower in the cell culture supernatant of KC-Keratocytes. In HCFs and KC-HCFs, protein levels of MMP-1 and TIMP-1 were higher and MMP-2 was lower compared to Keratocytes and KC-Keratocytes, respectively., Conclusion: This study indicates an imbalance in MMP and TIMP expression between healthy and diseased cells. Furthermore, differences in the expression of MMPs and TIMPs exist between corneal fibroblasts and keratocytes, which could influence the specific proteolytic metabolism in-vivo and contribute to the progression of KC., (© 2024. The Author(s).)

Purpose: To report functional and refractive outcomes of manual arcuate keratotomy (AK) with compression sutures for high regular postkeratoplasty astigmatism.Setting: not specified (review)., Design: Retrospective analysis., Methods: This study included 90 eyes with high regular postkeratoplasty astigmatism (>4 diopters, D) who received AK with compression sutures between 2010 and 2022. Functional and refractive outcomes were assessed by evaluating topographic indices and by performing vector astigmatism and Fourier analysis., Results: At last follow-up (mean=13.7±16.6 months), BCDVA improved from 0.59±0.28 logMAR to 0.34±0.25 logMAR. Cylinder magnitude decreased from 9.91±2.88 D to 5.42±3.35 D. Surface Asymmetry Index, Irregular Astigmatism Index, Corneal Eccentricity Index were equal to preoperative values, whereas Surface Regularity Index approached normal values at last follow-up. Fourier analysis indicated a decrease in the regular astigmatic component, whereas non-regular components (asymmetry and higher-order irregularity) remained stable. In vector astigmatism analysis, Target Induced Astigmatism magnitude was 9.92±2.86 D and Surgically Induced Astigmatism magnitude was 10.16±4.86 D (Correction Index of 0.91±0.48) with a Difference Vector of 5.42±3.35 D at last follow-up. Correction of astigmatism magnitude was adequate in 40% of the eyes, under-corrected in 30% and over-corrected in 30%. Angle of Error was <|22.5°| in 88% resulting in a low risk of off-axis treatment., Conclusion: AK with compression sutures is a simple, relatively effective and safe surgical procedure for astigmatism reduction after keratoplasty. In case of regular astigmatism, the procedure does not increase corneal irregularities. The remaining refractive error might be further corrected by spectacles, contact lenses or toric IOL implantation (in-the-bag / add-on), thus reducing the need for repeat keratoplasty., (Copyright © 2024 Published by Wolters Kluwer on behalf of ASCRS and ESCRS.)

Purpose: This study investigated the influence of cleanroom conditions on the discard rates of donor corneas in a German university eye bank., Methods: Discard rates were analysed from 2017 to 2020 at the LIONS Cornea Bank at Saarland University Medical Center. 1941 corneas from 971 donors were included. 1262 corneas (65.1%) were stored in a class D cleanroom from 2017 to 2019 and processed in a cleanroom class A sterile bank (group 1). 679 corneas (34.9%) were continuously stored in a class B cleanroom and processed in a class A cleanroom safety cabinet in the same room from 2019 to 2020 (group 2). The target parameter of this work was the number of contamination-related discards. Although they cannot be influenced by the spatial conditions, the discards due to insufficient endothelial quality, serology, contraindications, scars and technical causes were also recorded. Statistical analysis was performed using SPSS and various testing procedures., Results: In group 1, significantly more corneas were discarded due to positive serology (6.9%|3.8%, p = 0.020). There was no significant change between both groups for either contamination or the other reasons for discard., Conclusion: Optimization of hygiene standards from cleanroom class D to B did not reduce contamination. Serology, endothelial quality, medical contraindications and the presence of scars cannot be influenced by cleanroom conditions., (© 2023 The Authors. Acta Ophthalmologica published by John Wiley & Sons Ltd on behalf of Acta Ophthalmologica Scandinavica Foundation.)

Purpose: Assessment of tomographic characteristics and interdevice comparability between Scheimpflug imaging (Pentacam HR, Oculus Optikgeräte GmbH, Wetzlar, Germany) and swept-source optical coherence tomography (CASIA2, Tomey Corp., Nagoya, Japan) in eyes with macular corneal dystrophy (MCD)., Methods: Eyes with MCD were examined by Pentacam HR and CASIA2. Interdevice comparison was performed using a Wilcoxon matched pairs test and Bland-Altman plots with 95% limit of agreement. A Spearman rank correlation coefficient was used for correlating indices of both devices., Results: This retrospective study included 31 eyes of 18 patients (mean age: 32.1 ± 10.7 years). Eyes with MCD demonstrated a moderate astigmatism with a Cylinder anterior of 2.56 ± 1.50 D (Pentacam HR) and 2.52 ± 1.57 D (CASIA2) without a difference between both devices. CASIA2 (0.34 ± 0.14 D) measured lower values of Cylinder posterior compared with Pentacam HR (0.96 ± 0.66 D) (P < 0.0001). Comparison of pachymetry (Pentacam HR vs. CASIA2) showed higher values of the central corneal thickness (619 ± 227 μm vs. 445 ± 67 μm, P = 0.0001) and the thinnest corneal thickness (499 ± 165 μm vs. 430 ± 60 μm, P = 0.0167) for Pentacam HR. Corneal densitometry measurement revealed that increasing gray scale units caused a greater interdevice difference for pachymetry values, as Pentacam HR measured higher than CASIA2 for more opaque corneas., Conclusions: Eyes with MCD tend to have thinner corneas and a higher amount of corneal astigmatism than healthy eyes. In advanced MCD, Scheimpflug technology may mistakenly overestimate corneal thickness. The pachymetry measurement of the optical coherence tomography should be used when planning corneal surgery such as excimer laser-assisted phototherapeutic keratectomy to determine the ablation depth., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Until recently, corneal topography has been the gold standard in detecting keratectasia and monitoring its progression. The recently introduced ABCD tomographic keratoconus staging system focuses on anterior ("A") and posterior ("B") radius of curvature, thinnest corneal thickness ("C"), best-corrected visual acuity with spectacles ("D") and is supplemented with the introduction of the biomechanical E-staging (BEST, "E"). The need for biomechanical staging arose from the fact of altered biomechanical characteristics of keratectasia in comparison to healthy corneas. Ectatic corneas usually exhibit a biomechanical weakening and greater deformation than healthy corneas when exposed to a biomechanical stressor such as a standardized air puff indentation as provided by the Corvis ST® (CST, Oculus, Wetzlar, Germany). The BEST is based on the linear term of the Corvis Biomechanical Index (CBI) and provides a biomechanical keratoconus severity staging and progression assessment within the CST software. This review traces the development of the BEST as an addition to the tomographic ABCD staging system and highlights its strengths and limitations when applied in daily practice for the detection, monitoring and progression assessment in keratectasia., (© 2024. The Author(s).)

Purpose: To investigate expression of cytokines and ROS-related genes in stromal cells of healthy and keratoconus (KC) corneas., Methods: Expression analysis was performed for cytokines including several interleukins (IL), Tumor necrosis factor-α (TNF-α), Transforming growth factor-β1 (TGF-β1), Interferon-γ (IFN-γ) and ROS-related genes such as Catalase, Glutathione peroxidase 1, NADPH oxidase 1, superoxide dismutase 1 in corneal fibroblasts (HCFs/KC-HCFs) or keratocytes (Keratocytes/KC-Keratocytes) by qPCR and ELISA., Results: Gene and protein expression of most inflammatory markers was decreased in keratocytes compared to fibroblasts, whereas no differences were found between healthy and keratoconus cells for the majority of cytokines measured. TNF-α expression was increased at gene (KC keratocytes) and protein levels (supernatant of Keratocytes/KC-Keratocytes) compared to corneal fibroblasts. No differential expression of ROS-related genes was detected between healthy and diseased cells in both fibroblasts and keratocytes., Conclusion: Increased expression of several inflammatory markers described as altered in KC was not evident in KC cells in vitro .

Purpose: The aim of this study was to analyze changes in corneal biomechanical properties after implantation of intracorneal ring segments (ICRSs) in keratectasia., Methods: This retrospective single-center study included 112 patient eyes that underwent femtosecond laser-assisted ICRS implantation (Intacs SK; Addition Technology Inc, Des Plaines, IL) for keratectasia. Biomechanical analysis was performed using the Ocular Response Analyzer (ORA; Reichert Inc, Depew, NY), with determination of corneal resistance factor, corneal hysteresis, and Keratoconus Match Index, as well as by Corvis ST (OCULUS, Wetzlar, Germany), with determination of stiffness parameter A1, Ambrosio relational thickness to the horizontal profile (Arth), integrated radius, deformation amplitude ratio, and stress-strain index as well as Corvis Biomechanical Index and Tomographic Biomechanical Index. Data collection was performed preoperatively and 6 months postoperatively for ORA and Corvis ST and additionally after 1 and 2 years for ORA., Results: The corneal resistance factor decreased significantly postoperatively (5.8 ± 1.7 mm Hg) compared with preoperatively (6.75 ± 3.7 mm Hg; P = 0.021) and increased again during follow-up (6.2 ± 1.9 mm Hg; P = 0.024), without regaining preoperative values. Corneal hysteresis and Keratoconus Match Index did not change significantly. Stiffness parameter A1 ( P = 0.045) increased significantly after ICRS implantation and Arth decreased significantly from 181 ± 85 to 150 ± 92 ( P = 0.016). However, there was no significant postoperative change for others Corvis parameters., Conclusions: Corneal biomechanical properties showed inconsistent changes after ICRS implantation. Classical corneal biomechanical parameters (using single central air-puff tonometers) do not seem to be suitable for follow-up after ICRS implantation., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

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., (© 2024. The Author(s).)

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., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

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., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background/aims: This retrospective multicentric panel study provides absolute numbers, types of and indications for corneal transplantation in Germany from 2011 to 2021 and sets them into the international context., Methods: A questionnaire was sent to the 104 German ophthalmologic surgery departments and 93 (89%) provided their data., Results: The number of reported keratoplasties more than doubled from 2011 (n=4474) to 2021 (n=8998). Lamellar keratoplasties (49% posterior (n=2883), 4% anterior (n=231)) surpassed penetrating keratoplasty (PKP, 47%, n=2721) for the first time in 2014. Since 2016, Descemet's membrane endothelial keratoplasty (DMEK) has become the predominant keratoplasty procedure in Germany. Its number increased by 1.5-fold from 3850 (2016) to 5812 (2021). Main indications in 2021 were Fuchs' endothelial corneal dystrophy (FECD, 43%), pseudophakic corneal decompensation (12%), repeated keratoplasty (11%), infections (7%), keratoconus (6%) and corneal scarring (4%, others: 9%). The PKP percentage decreased from 70.2% in 2011 (n=3141) to 31.7% in 2021 (n=2853). Descemet's stripping (automated) endothelial keratoplasties (DSAEKs) decreased to 1% in 2021 (n=74). 98.6% of all posterior lamellar keratoplasties were DMEKs in Germany in 2021. The number of deep anterior lamellar keratoplasties (DALKs) remained comparable from 2011 (n=269) to 2021 (n=251, 2.8%)., Conclusion: Main indications for corneal transplantation in Germany (2021) were FECD and pseudophakic corneal decompensation. DMEK is by far the predominant corneal transplantation procedure since 2016 followed by PKP, whose absolute number decreased only slightly during the decade from 2011 to 2021. DALK proportions remain low, but stable, whereas DSAEK decreased annually and plays a minor role in Germany., Trial Registration Number: NCT03381794., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

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., (Copyright © 2024 Copyright: © 2024 Indian Journal of Ophthalmology.)

Purpose: To provide insights into morphologic and functional features of eyes with complicated Descemet's membrane detachment (DMD) and report clinical outcomes after surgical intervention., Methods: Retrospective study of 18 eyes with complicated DMD between 2010 and 2022. Complicated DMD was defined if any of the following criteria applied: prior penetrating keratoplasty (PKP), corneal thinning, total DMD or persistent DMD after Air/Gas-Descemetopexy. Causes, surgical management, and clinical outcomes were analyzed. Scheimpflug tomography, anterior segment optical coherence tomography (AS-OCT) and histologic examination were performed to characterize corneas with DMD., Results: Fourteen eyes with prior PKP developed spontaneous DMD after 24.2 ± 12.9 years (range = 18 months - 47 years, median = 25.7 years). Complicated DMD without prior PKP was associated in three eyes after cataract surgery and in one eye after infectious keratitis. In cases with previous PKP, AS-OCT demonstrated rupture of Descemet's membrane (DM) in five eyes and spontaneous reattachment was found in four eyes within 8 weeks of initial diagnosis, with no rupture of DM in any of the cases. There was no rupture of DM in corneas without previous PKP. After prior keratoplasty, definitive surgical treatment was repeat PKP in 13 eyes and Air/Gas-Descemetopexy in one eye. In corneas without prior keratoplasty, three eyes underwent PKP and one eye Air/Gas-Descemetopexy. Histological examination of two corneal explants revealed a severely thinned graft-host junction and a disrupted DM close to the graft-host junction. Visual acuity improved from 1.80 ± 0.58 logMAR to 0.75 ± 0.69 logMAR after prior PKP and from 1.45 ± 0.65 logMAR to 0.85 ± 1.13 logMAR without prior PKP. The postoperative course was uneventful in 16 of 18 eyes., Conclusion: PKP is an effective treatment option for complicated DMD, especially in ectatic corneas, whereas Air/Gas-Descemetopexy or Descemet Membrane Endothelial Keratoplasty do not address the primary issue of the curvature anomaly., (© 2023. The Author(s).)

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., (© 2024 The Authors. Journal of Medical Virology published by Wiley Periodicals LLC.)

Purpose: The aim of this study is to compare the healing of corneal epithelial defects or ulcers on the corneal graft in comparison with the patient's own cornea after treatment with 100%, undiluted autologous serum eye drops., Methods: In a retrospective study over 7 years, we analysed 263 treatments with autologous serum eye drops of persistent corneal epithelial defects (erosions [88%] vs. ulcers [12%]). We compared the epithelial healing tendency of patients with defects on their own cornea (51.9%) vs. patients who had previously undergone penetrating keratoplasty (48.1%). Complete epithelial healing during the 28 days of treatment was considered as therapeutic success. In addition, the recurrence rate of the epithelial defects after finishing the therapy was analysed., Results: 88.2% of the epithelial defects healed during 28 days of therapy. The recurrence rate during follow-up was 5.1%. There was no significant difference with respect to success rate between corneal defects on the patient's own cornea (87.8%) and on the graft (88.6%; p = 0.137). There was a significantly lower success rate for corneal ulcers (74.2%) than for erosions (90.3%; p < 0.001). The recurrence rate of erosions was 4.4%, vs. 4.3% in ulcers during follow-up., Conclusion: The results of our study suggest that autologous serum eye drops are a non-invasive and safe alternative treatment for persistent corneal epithelial defects - with no significant difference in patients with a defect on their own cornea vs. defects on the corneal graft. The success rate, but not the recurrence rate, is significantly worse in ulcers than in erosions., Competing Interests: Die Autorinnen/Autoren geben an, dass kein Interessenkonflikt besteht., (Thieme. All rights reserved.)

Corneal diseases include a wide spectrum of different manifestations (inflammatory/noninflammatory) that need to be accurately classified for precise diagnosis and targeted treatment. In addition to the anamnesis and slit lamp biomicroscopy, further device-based examinations can be performed to narrow down the diagnosis. Nowadays, modern corneal imaging provides a variety of technologies, such as topography, tomography, in vivo confocal microscopy and analysis of biomechanics, which are able to reliably classify different pathologies. Knowledge of the available examination modalities helps to guide differential diagnostic considerations, facilitating the indication for stage-appropriate microsurgical intervention., (© 2023. The Author(s).)

Background and Purpose: The etiology of keratoconus (KC) is probably multifactorial but remains essentially unknown. Previous scientific observations have suggested that hypothyroidism might play a role in the development and progression of KC. The purpose of this study was to analyze the tomographic and biomechanical parameters in KC patients with or without hypothyroidism., Methods: Twenty-eight patients with KC and hypothyroidism (HT group) and fifty-six KC patients without thyroid dysfunction (WHT group) with matching gender and age were analyzed. Mean age was 40.3 years (range 14 - 57) in the HT group and 40.3 years (range 14 - 57) in the WHT group. Routine ophthalmic examinations consisted of corneal tomography and biomechanical parameters. We extracted the following KC parameters from the Pentacam (Pentacam HR, Oculus, Wetzlar, Germany): Keratoconus Index (KI), maximum keratometry (K max ), astigmatism, and thinnest pachymetry (TP). From the ocular response analyzer (ORA, Reichert Ophthalmic Instruments, Depew, NY, USA), we extracted corneal hysteresis (CH), corneal resistance factor (CRF), and KC match index (KMI)., Results: The comparison of the tomographic and biomechanical values from cross-sectional and longitudinal analyses showed no significant differences between the HT and WHT groups., Conclusion: The severity of KC based on tomographical and biomechanical parameters does not seem to depend on the presence of hypothyroidism., Competing Interests: The authors declare that they have no conflict of interest., (Thieme. All rights reserved.)

Purpose: To evaluate the efficacy of accelerated (9 mW/cm 2 , 10 min) epithelium-off (epi-off) corneal crosslinking (A-CXL) in keratoconus (KC) patients < 18 years of age., Patients and Methods: Our retrospective study included 41 eyes (25 male and 5 female patients, mean age 15.3 ± 1.2 years) who underwent A-CXL (9 mW/cm 2 , 10 min) because of progressive KC or critical KC at first presentation or asymmetrical finding in the partner eye. Outcome measures were best-corrected visual acuity (BCVA) and tomography readings (Pentacam HR, Oculus, Wetzlar, Germany), evaluated 2 years, 1 year, 6 months preoperatively, prior to surgery (pre-CXL) and 6 weeks, 6 months, 1 year, 2 years, > 2 years postoperatively (post-CXL). The demarcation line was assessed by anterior segment optical coherence tomography (SS-1000 and CASIA 2, Tomey, Nagoya, Japan)., Results: Total deviation value increased statistically significantly 6 months pre-CXL to pre-CXL. Anterior steep, flat, and mean keratometry values showed a statistically significant increase 6 weeks post-CXL (p < 0.05), followed by a significant decrease until 2 years post-CXL for steep and mean keratometry. K max increased 6 weeks post-CXL without statistical significance and decreased significantly even > 2 years post-CXL (p < 0.0001). Posterior keratometry as well as anterior and posterior astigmatism did not show any significant changes post-CXL. Thinnest and apical pachymetry decreased significantly until 6 months post-CXL (p < 0.05) and remained stable > 2 years post-CXL (p > 0.05). BCVA decreased 6 weeks post-CXL but improved significantly > 2 years post-CXL (p = 0.003). The demarcation line reached an average depth of 52.1%., Conclusions: Epi-off A-CXL stabilizes KC progression in patients < 18 years even > 2 years postoperatively and leads to a deep demarcation line. A "pseudoprogression" is observed up to the 6-week follow-up, which is not indicative of the long-term results., Competing Interests: E. Flockerzi has received a travel grant to the Second and Third Ophthalmology Cystinosis Forum (Orphan Europe, Ulm, Germany) and an invitation to a seminar on presentation training organized by Santen GmbH (Munich, Germany). The remaining authors have no conflicts of interest to disclose., (Thieme. All rights reserved.)

Objective: The aim of this study was to analyze the effect of corneal cross-linking (CXL) on corneal biomechanics and visual acuity., Patients and Methods: The examination results before and after CXL in 56 eyes of 56 patients between 2017 and 2021 were evaluated retrospectively. The last preoperative examination was compared to the postoperative follow-up values after 6 and 12 months. The main outcome measures included various biomechanical parameters from the Corvis ST (CST), Pentacam and the visual acuity (logMAR, "logarithm of the Minimal Angle of Resolution"). For longitudinal evaluation, a general linear model for repeated measurements was used. A p-value of less than 0.05 was considered to show a statistically significant result. Bonferroni correction was applied for multiple comparisons., Results: The maximum corneal refractive power K max decreased slightly without statistical significance from 57.1 ± 6.1 diopters (dpt) to 56.6 ± 6.3 dpt after 6 months (p = 0.076) and 56.8 ± 6.6 dpt after 12 months (p = 0.443). The Pentacam parameter Belin/Ambrósio Enhanced Ectasia Total Deviation Display (BAD D) showed a statistically significant increase from the preoperative value of 8.4 ± 3.7 to the postoperative value of 9.1 ± 3.6 after 6 months (p < 0.001) and to 8.9 ± 3.5 after 12 months (p = 0.051). The CST parameter Ambrósio's relational thickness to horizontal profile (ARTh) decreased statistically significantly from 229.9 ± 109.6 to 204.8 ± 84.9 at 6 months (p = 0.017) and 205.3 ± 93.7 at 12 months (p = 0.022). The CST parameter stiffness parameter A1 (SP A1) increased slightly from the preoperative value 69.9 ± 17.2 to 70.4 ± 17.2 after 6 months (p = 1) and 71 ± 18.2 after 1 year (p = 1). Mean best-corrected visual acuity (logMAR) showed an improvement from 0.39 ± 0.3 to 0.34 ± 0.3 at 6 months (p = 0.286) and to 0.31 ± 0.3 at 12 months (p = 0.077). Regarding the ABCD classification, the parameters were determined preoperatively with an average of A2B3C1D2. They showed the same value of A2B3C1D2 after 6 and 12 months., Conclusion: In progressive keratoconus, corneal cross-linking has the potential to positively influence the biomechanics of the cornea and visual acuity as a low complication treatment option., (© 2023. The Author(s).)

Objectives: The study objective was to analyze the baseline characteristics of keratoconus (KC) patients at the Homburg Keratoconus Center from 2010 to 2021., Methods: This cross-sectional study included 3,674 eyes, with analysis of demographics, clinical findings, visual function, endothelial measurements, and topographic, tomographic, and corneal biomechanical data from the first visit., Results: Mean patient age was 36.3±13.8 years. The mean uncorrected distance visual acuity in log of minimal angle of resolution was 0.60 (20/80, Snellen equivalent), and the corrected mean was 0.3 (20/40). Of 1976 patients, 48.9% reported eye rubbing. Mean values (ranges) were 49.4±6.3 (36.3-78.0) D for steep keratometry, 462.4±66.0 (48.0-659.0) μm for thinnest corneal thickness, 9.7±8.7 (-0.5 to 88.8) for Belin/Ambrósio enhanced ectasia total deviation, 0.8±0.4 (0.0-1.0) for the Corvis biomechanical index, 0.9±0.2 (0.0-1.0) for the tomographic biomechanical index, 0.1±0.5 (-0.9 to 2.0) for the KC match index, 8.3±1.8 (2.2-17.7) mm Hg for corneal hysteresis, 7.1±2.2 (0.0-17.0) mm Hg for corneal resistance factor, and 2,562.9±326.3 (1,011-3,937) cells/mm2 for endothelial cell density. The average ABCDE KC stage was A2B3C1D1E2. Distance-corrected visual acuity correlated strongly with topometric, tomographic, and biomechanical data ( P <0.001)., Conclusions: This comprehensive description of baseline features of KC patients at a tertiary center provides a reference for further longitudinal and international multicentric studies., Competing Interests: The authors have no conflicts of interest to declare., (Copyright © 2023 Contact Lens Association of Ophthalmologists.)

Introduction: Simulation training has an important role in medical education. In ophthalmology, simulation-based training has been shown to be significantly effective for surgical and diagnostic training in direct and indirect ophthalmoscopy. In this study, we analysed the effects of simulator-based slit lamp training., Methods: In this prospective controlled trial, medical students in their eighth semester at Saarland University Medical Center (n = 24) who had attended a 1-week ophthalmological internship were randomized into two groups: The traditional group (n = 12) was examined directly after the 1-week internship; the simulator group (n = 12) was trained with the slit lamp simulator before passing an objective structured clinical examination (OSCE). A masked ophthalmological faculty trainer assessed the students' slit lamp skills (maximum total score 42 points [pts]): preparation (5 pts), clinical examination (9.5 pts), assessment of findings (9.5 pts), diagnosis (3 pts), commentary on the examination approach (8 pts), measurement of structures (2 pts) and recognition of five diagnoses (5 pts). All students completed post-assessment surveys. Examination grades and survey responses were compared between the groups., Results: The overall performance of the slit lamp OSCE was significantly better (p < 0.001) in the simulator group than in the traditional group (29.75 [7.88] vs. 17.00 [4.75]) with significantly higher scores for the preparation and assessment of slit lamp controls (5.0 [0.0] vs. 3.0 [3.5]; p = 0.008) and localization of relevant structures (6.75 [3.13] vs. 4.0 [1.5]; p = 0.008). Consistently higher scores, but not significant, were assigned for the description of structures found (4.5 [3.38] vs. 3.25 [2.13]; p = 0.09) and the correct diagnosis (3.0 [0.0] vs. 3.0 [0.0]; p = 0.48). Surveys reflected the students' subjectively perceived knowledge gain during the simulator training for slit lamp illumination techniques (p = 0.002), recognition (p < 0.001), and assessment of the correct localization of pathologies (p < 0.001)., Conclusion: Slit lamp examination is an important diagnostic method in ophthalmology. Simulator-based training improved students' examination techniques for localizing anatomical structures and pathological lesions. The transfer of theoretical knowledge into practice can be achieved in a stress-free atmosphere., (© 2023. The Author(s).)

Purpose: To optimize artificial intelligence (AI) algorithms to integrate Scheimpflug-based corneal tomography and biomechanics to enhance ectasia detection., Design: Multicenter cross-sectional case-control retrospective study., Methods: A total of 3886 unoperated eyes from 3412 patients had Pentacam and Corvis ST (Oculus Optikgeräte GmbH) examinations. The database included 1 eye randomly selected from 1680 normal patients (N) and from 1181 "bilateral" keratoconus (KC) patients, along with 551 normal topography eyes from patients with very asymmetric ectasia (VAE-NT), and their 474 unoperated ectatic (VAE-E) eyes. The current TBIv1 (tomographic-biomechanical index) was tested, and an optimized AI algorithm was developed for augmenting accuracy., Results: The area under the receiver operating characteristic curve (AUC) of the TBIv1 for discriminating clinical ectasia (KC and VAE-E) was 0.999 (98.5% sensitivity; 98.6% specificity [cutoff: 0.5]), and for VAE-NT, 0.899 (76% sensitivity; 89.1% specificity [cutoff: 0.29]). A novel random forest algorithm (TBIv2), developed with 18 features in 156 trees using 10-fold cross-validation, had a significantly higher AUC (0.945; DeLong, P < .0001) for detecting VAE-NT (84.4% sensitivity and 90.1% specificity; cutoff: 0.43; DeLong, P < .0001) and a similar AUC for clinical ectasia (0.999; DeLong, P = .818; 98.7% sensitivity; 99.2% specificity [cutoff: 0.8]). Considering all cases, the TBIv2 had a higher AUC (0.985) than TBIv1 (0.974; DeLong, P < .0001)., Conclusions: AI optimization to integrate Scheimpflug-based corneal tomography and biomechanical assessments augments accuracy for ectasia detection, characterizing ectasia susceptibility in the diverse VAE-NT group. Some patients with VAE may have true unilateral ectasia. Machine learning considering additional data, including epithelial thickness or other parameters from multimodal refractive imaging, will continuously enhance accuracy. NOTE: Publication of this article is sponsored by the American Ophthalmological Society., (Copyright © 2022. Published by Elsevier Inc.)

Purpose: To report a case of corneal perforation as a rare and late manifestation of choroidal melanoma and to highlight the major histopathological findings of this unusual combined clinical presentation., Methods: A 74-year-old male patient presented to our department due to corneal perforation of the right eye with the absence of light perception for 6 months. The intraocular pressure was hard on palpation. Because of the protracted finding and reduced visual prognosis, primary enucleation was performed., Results: The histopathological examination revealed choroidal melanoma with epithelioid and spindle cell components at the posterior pole, which was positive for Melan-A, Human Melanoma Black 45 (HMB45), BAP1, and SOX10. The anterior segment showed complete anterior chamber hemorrhage and blood remnants in the trabecular meshwork. The cornea displayed diffuse blood staining with hemosiderin and hemosiderin-loaded macrophages and keratocytes. No inflammatory cells were present near the corneal perforation, which had a width of 3 mm. Intraocular heterotopic ossification was indicative of a long-standing condition. Postoperative cancer staging was normal., Conclusion: Corneal perforation should be considered as a very rare and late manifestation of advanced choroidal melanoma and may result from interaction between intraocular hemorrhage, elevated IOP, and its secondary signs such as corneal blood staining., Competing Interests: The authors declare that they have no conflict of interest., (Thieme. All rights reserved.)

Purpose: Intraocular pressure (IOP) measurement may be difficult in keratoconus (KC) due to corneal protrusion and irregular astigmatism. This study aimed to assess which IOP measurement modality is least affected by KC severity., Methods: Data from 246 corneas of 246 patients with KC were retrospectively analyzed. KC stages were determined using the Topographic KC (TKC) and ABCD KC classifications derived from Pentacam (Oculus, Germany). IOP was measured using Goldmann applanation tonometry (GAT), Ocular Response Analyzer (ORA, Reichert Instruments, USA), and Corvis ST (CST, Oculus, Germany). Cronbach alpha (CA), analysis of variance with Bonferroni correction, Dunnett T3, and Pearson correlation were performed., Results: Using CA, the reliability of measurements using various modalities increased to 0.764 to 0.943 when excluding IOP Goldmann overall and in each KC stage (TKC and ABCD). Analysis of variance revealed significant differences between TKC and ABCD stages for almost all IOP modalities. The Bonferroni post hoc test showed significant differences between the measured IOP in earlier and advanced KC stages, except for the biomechanically CST-corrected IOP (bIOP). Pearson correlation analysis showed a significant correlation between IOP and thinnest corneal thickness (TCT) for all IOP modalities except bIOP., Conclusions: CST-based bIOP seems to be best suited for IOP measurement in KC because it did not correlate with TCT in contrast to IOP measurements by ORA or GAT. The measurement results from GAT in patients with KC should be interpreted with care and always in view of corneal thickness. As a thumb rule, we suggest to add at least 2 mm Hg to the measured GAT value., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)