Bioinformatics analysis of signature genes related to cell death in keratoconus.

Keratoconus is corneal disease in which the progression of conical dilation of cornea leads to reduced visual acuity and even corneal perforation. However, the etiology mechanism of keratoconus is still unclear. This study aims to identify the signature genes related to cell death in keratoconus and examine the function of these genes. A dataset of keratoconus from the GEO database was analysed to identify the differentially expressed genes (DEGs). A total of 3558 DEGs were screened from GSE151631. The results of Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis showed that they mainly involved in response to hypoxia, cell-cell adhesion, and IL-17 signaling pathway. Then, the cell death-related genes datasets were intersected with the above 3558 DEGs to obtain 70 ferroptosis-related DEGs (FDEGs), 32 autophagy-related DEGs (ADEGs), six pyroptosis-related DEGs (PDEGs), four disulfidptosis-related DEGs (DDEGs), and one cuproptosis-related DEGs (CDEGs). After using Least absolute shrinkage and selection operator (LASSO), Random Forest analysis, and receiver operating characteristic (ROC) curve analysis, one ferroptosis-related gene (TNFAIP3) and five autophagy-related genes (CDKN1A, HSPA5, MAPK8IP1, PPP1R15A, and VEGFA) were screened out. The expressions of the above six genes were significantly decreased in keratoconus and the area under the curve (AUC) values of these genes was 0.944, 0.893, 0.797, 0.726, 0.882 and 0.779 respectively. GSEA analysis showed that the above six genes mainly play an important role in allograft rejection, asthma, and circadian rhythm etc. In conclusion, the results of this study suggested that focusing on these genes and autoimmune diseases will be a beneficial perspective for the keratoconus etiology research.

[Current aspects of vernal and atopic keratoconjunctivitis]. / Aktuelles zur Keratoconjunctivitis vernalis und atopica.

BACKGROUND: Vernal keratoconjunctivitis (VKC) and atopic keratoconjunctivitis (AKC) are complex and rare diseases. Thus, their diagnosis and treatment are often a challenge. OBJECTIVE: Discussion on the epidemiology, new pathogenetic concepts, interesting clinical findings, diagnostic possibilities and new treatment options and their side effects in severe ocular allergies. Analysis of the presentation of VKC in the internet. MATERIAL AND METHODS: Evaluation of recent review articles, original publications, and case reports on the topics of VKC and AKC over the past 5 years. RESULTS: Ocular allergies have significantly increased over the last decades. Recent concepts discussed in the pathogenesis of VKC and AKC are the role of the local and gut microbiome as well as the influence of neuroinflammation. Keratoconus is significantly more common in patients with VKC and AKC compared to the normal population. It is associated with faster progression and a more severe course of disease. A conjunctival provocation test is only rarely necessary in the diagnosis of allergic conjunctivitis. Treatment of atopic dermatitis with dupilumab, an interleukin 4 receptor alpha (IL-4Ra) antagonist, can cause ocular side effects. Unfortunately, information available on the internet for patients and parents on the topic of VKC is sometimes dangerously incorrect. CONCLUSION: From the abovementioned new pathogenetic concepts, preventive and personalized treatment options could be developed in the future. Keratoconus in AKC/VKC must be recognized and treated early. Official guidelines are now available for a standardized conjunctival provocation test in the diagnosis of allergic conjunctivitis. The unwanted ocular side effects of dupilumab are often difficult to discriminate from the actual underlying AKC and respond well to anti-inflammatory treatment. Patients with VKC must be informed about the incorrect information on the internet regarding their disease.

Is Keratoconus More Than Just a Corneal Disease?

PURPOSE: The aims of this study were to compare the scleral thickness (ST), lamina cribrosa thickness (LCT), and lamina cribrosa curvature index between patients with keratoconus and healthy controls and to evaluate the relationship between these values and corneal parameters. METHODS: This cross-sectional study included 41 eyes of 41 patients with keratoconus and 30 eyes of 30 age-matched, sex-matched, and axial length-matched controls. Nasal and temporal STs were measured vertically, 4 mm posterior to the scleral spur, using anterior segment optical coherence tomography. The LCT was measured on the radial scans of the optic nerve head. The lamina cribrosa curvature index (lamina cribrosa curvature depth/curvature width × 100) was calculated to determine the degree of posterior bowing of the lamina cribrosa. RESULTS: The nasal ST and temporal ST were significantly lower in the keratoconus group than in the control group ( P = 0.016 and P = 0.023, respectively). The LCT was significantly lower in the keratoconus group compared with the control group ( P < 0.001). There was no significant difference between the groups for the lamina cribrosa curvature index ( P = 0.375). Correlation analysis revealed a significant correlation between the nasal and temporal STs and the central corneal thickness (r = 0.376, P < 0.001 and r = 0.387, P < 0.001, respectively). There was also a significant correlation between the temporal ST and the minimum corneal thickness in the keratoconus group (r = 0.332, P = 0.015). The LCT was significantly correlated with the central corneal thickness (r = 0.445, P < 0.001). CONCLUSIONS: Structural features of the cornea, sclera, and lamina cribrosa with similar collagen content may be similarly affected in patients with keratoconus. Further histologic studies are needed to confirm our results.

Association of torpedo maculopathy and keratoconus in a young patient: A multimodal imaging study.

PURPOSE: To report and document a case of torpedo maculopathy found in a patient affected by keratoconus.Case report: An healthy 16-year-old male patient, affected by keratoconus in both eyes, was referred to the cornea service of our hospital for a follow-up visit.During the dilated fundus examination of the left eye, an oval, well-demarcated, hypopigmented lesion was observed in the juxtafoveal temporal region, pointing towards the center of the macula. Multimodal imaging of the lesion was performed, and the diagnosis of Torpedo Maculopathy was established based on the clinical picture. CONCLUSION: This is the first case of torpedo maculopathy described in a patient affected by keratoconus. This association may be merely fortuitous or the result of developmental abnormalities affecting both corneal and retinal structures.

Sequence variants contributing to dysregulated inflammatory responses across keratoconic cone surface in adolescent patients with keratoconus.

Background: Keratoconus (KTCN) is the most common corneal ectasia resulting in a conical shape of the cornea. Here, genomic variation in the corneal epithelium (CE) across the keratoconic cone surface in patients with KTCN and its relevance in the functioning of the immune system were assessed. Methods: Samples from four unrelated adolescent patients with KTCN and two control individuals were obtained during the CXL and PRK procedures, respectively. Three topographic regions, central, middle, and peripheral, were separated towards the whole-genome sequencing (WGS) study embracing a total of 18 experimental samples. The coding and non-coding sequence variation, including structural variation, was assessed and then evaluated together with the previously reported transcriptomic outcomes for the same CE samples and full-thickness corneas. Results: First, pathway enrichment analysis of genes with identified coding variants pointed to "Antigen presentation" and "Interferon alpha/beta signaling" as the most overrepresented pathways, indicating the involvement of inflammatory responses in KTCN. Both coding and non-coding sequence variants were found in genes (or in their close proximity) linked to the previously revealed KTCN-specific cellular components, namely, "Actin cytoskeleton", "Extracellular matrix", "Collagen-containing extracellular matrix", "Focal adhesion", "Hippo signaling pathway", and "Wnt signaling" pathways. No genomic heterogeneity across the corneal surface was found comparing the assessed topographic regions. Thirty-five chromosomal regions enriched in both coding and non-coding KTCN-specific sequence variants were revealed, with a most representative 5q locus previously recognized as involved in KTCN. Conclusion: The identified genomic features indicate the involvement of innate and adaptive immune system responses in KTCN pathogenesis.

Automated cornea diagnosis using deep convolutional neural networks based on cornea topography maps.

Cornea topography maps allow ophthalmologists to screen and diagnose cornea pathologies. We aim to automatically identify any cornea abnormalities based on such cornea topography maps, with focus on diagnosing keratoconus. To do so, we represent the OCT scans as images and apply Convolutional Neural Networks (CNNs) for the automatic analysis. The model is based on a state-of-the-art ConvNeXt CNN architecture with weights fine-tuned for the given specific application using the cornea scans dataset. A set of 1940 consecutive screening scans from the Saarland University Hospital Clinic for Ophthalmology was annotated and used for model training and validation. All scans were recorded with a CASIA2 anterior segment Optical Coherence Tomography (OCT) scanner. The proposed model achieves a sensitivity of 98.46% and a specificity of 91.96% when distinguishing between healthy and pathological corneas. Our approach enables the screening of cornea pathologies and the classification of common pathologies like keratoconus. Furthermore, the approach is independent of the topography scanner and enables the visualization of those scan regions which drive the model's decisions.

Ophthalmic Manifestations of Arterial Tortuosity Syndrome: Case Series of Patient and Carriers.

PURPOSE: The aim of this study was to report the detailed ophthalmic findings in a young patient with genetically confirmed arterial tortuosity syndrome (ATS) and the findings in 8 family members who were carriers. METHODS: Nine members of the same Saudi family were assessed at King Khaled Eye Specialist Hospital in Riyadh, Saudi Arabia, for ATS-related ocular changes after homozygosity for the pathogenic variant of SLC2A10 gene was confirmed in 1 member. All family members underwent complete ophthalmic examination, genetic testing, and corneal tomography at presentation and at 6-month follow-up. RESULTS: All ophthalmic features were manifested in our patient with ATS including schisis-like splitting of the stromal layer with greater peripheral thinning, pannus, deep posterior stromal opacities, myopia, high astigmatism, and keratoglobus. The ocular phenotype was also expressed in some carriers ranging from mild myopia to the full spectrum of corneal abnormalities associated with ATS. CONCLUSIONS: Our study provided further insights into the phenotype in both patients with ATS and carriers. Annual ophthalmic examination is warranted in both types of patients and must undergo from early life onward to detect progressive ectasia which may necessitate corneal crosslinking.

Corneal topography in preterm children aged 2 years to 12 years with or without retinopathy of prematurity.

OBJECTIVES: To evaluate corneal topography in full-term and preterm children with or without retinopathy of prematurity (ROP). METHODS: We enrolled children aged from 2 years to 12 years between January 2019 and May 2021 in the following four groups: full-term (group 1), premature without ROP (group 2), untreated premature with ROP (group 3), and laser-treated and/or intravitreal injection (IVI) of anti-vascular endothelial growth factor (VEGF)-treated premature with ROP (group 4). Corneal topography was measured with the Galilei Placido-dual Scheimpflug analyzer G4 every half year, and was compared among the groups using generalized estimating equation models at approximately 7 years of age. RESULTS: We included 77, 178, 45, and 131 participants in groups 1, 2, 3, and 4, respectively. The mean (standard deviation) number of visits per patient was 2.9 (1.4). Compared with full-term eyes, premature eyes demonstrated steeper anterior corneal curvature (p = 0.016 and p = 0.008 for the mean and steep K, respectively), higher anterior and posterior corneal astigmatism (p = 0.036 and p = 0.016, respectively), and thinner thinnest pachymetry (p < 0.001). The laser-treated ROP eyes displayed steeper anterior corneal curvature (p = 0.040 for steep K) and higher anterior corneal astigmatism (p = 0.005) than the IVI-treated eyes. Moreover, they exhibited high cone location and magnitude index (1.96) reaching the cut-off for detecting keratoconus (1.82). CONCLUSIONS: The premature status led to greater corneal ectasia, and laser treatment for ROP caused further corneal steepness. Higher anterior corneal astigmatism was associated with laser treatment. The ROP pathology and IVI anti-VEGF treatment exerted a marginal effect on corneal topography.

Corneal biomechanical stiffness and histopathological changes after in vivo repeated accelerated corneal cross-linking in cat eyes.

Corneal cross-linking (CXL) has been proved efficiency for treating progressive keratoconus and other corneal ectasia diseases by stabilizing corneal geometry and biomechanics. However, the necessity of repeated CXL treatment in patients is unknown. This study aimed to investigate corneal biomechanical stiffness and change in corneal histopathological characteristics after repeated accelerated CXL (A-CXL) in cat eyes. A-CXL was performed with 0.1% riboflavin applied for 10 min, followed by ultraviolet A irradiation at 30 mW/cm2 for 3 min at 365 nm in 15 domestic cats. Corneas (n = 30) were divided into three groups: one-time accelerated corneal cross-linking (A-CXL*1 group), repeated accelerated corneal cross-linking (A-CXL*2 group), and an untreated control group. In A-CXL*2 group, A-CXL was repeated at 1-month intervals. In vivo ocular examinations were performed pre- and postoperatively. Biomechanical analysis was performed using a biotester biaxial testing system. We used the Mooney-Rivlin strain-energy function to describe corneal material properties. No infection in any case after A-CXL was observed. Biomechanical tests showed that the stress-strain curves of the two A-CXL groups were significantly different from those of the control group (P < 0.01), whereas stress-strain curve of the A-CXL*2 group was similar to that of the A-CXL*1 group (P > 0.05). Delayed epithelial healing and haze were observed 1 month after surgery. Stromal demarcation line depth measured with anterior spectral-domain optical coherence tomography was 187.6 ± 20.4 and 197.1 ± 11.5 µm for the A-CXL*1 and A-CXL*2 groups, respectively (P > 0.05). These results show that A-CXL can increase corneal biomechanics in cat eyes. The biomechanical enhancement of cat corneas treated with repeated A-CXL at 1-month intervals was similar to that of performing a one-time A-CXL. Repeated cross-linking procedures at short intervals may increase the risk of adverse reactions, and more caution should be taken in clinical applications.

Differential Diagnosis of Keratoconus Based on New Technologies.

Keratoconus (KC) must be distinguished from other corneal ectatic diseases and thinning disorders for stage-appropriate and suitable management of each condition. The most relevant corneal pathologies that may imitate the tomographic KC pattern are pellucid marginal degeneration (PMD), keratoglobus, posterior keratoconus, and Fuchs-Terrien marginal degeneration (FTMD). In moderate cases of KC, differentiation is typically possible using slit lamp examination and corneal tomography with evaluation of the location of the corneal thinning region. In early cases, however, differential diagnosis may be more challenging since the cornea may look relatively normal. In severe cases, the extended area of corneal thinning also complicates differentiation. Biomicroscopic findings cannot always give all the information needed to distinguish KC from related ectatic corneal conditions. The aim of this work is to discuss contemporary techniques and findings to assist physicians to identify the correct diagnosis. Corneal topography has been used in recent decades as the main tool for imaging in ectatic corneal diseases. Moreover, Scheimpflug cameras (corneal tomographers), which analyze both anterior and posterior corneal surfaces, curvatures, pachymetry, elevation data, higher order aberrations, Fourier analysis of keratometric data, and corneal density have become the most promising tools for diagnosis and follow-up of ectatic diseases. A noninvasive air pulse tonometer in conjunction with an ultrahigh-speed Scheimpflug camera complements tomographic findings by analyzing biomechanical corneal properties. Α confocal microscopy system, which is a novel clinical technique for the study of corneal cellular structure, could contribute effectively in the same direction. Moreover, anterior segment optical coherence tomography (AS-OCT) creates cross-sections, which can be generated into a three-dimensional structure to produce corneal epithelial thickness (ET) measurements. ET mapping is increasingly recognized as a sensitive tool for the diagnosis of ocular surface disorders. Combining information of all these systems could lead to a more effective identification and differential diagnosis of ectatic corneal disorders.

Corneal Crosslinking: Present and Future.

Keratoconus is a progressive corneal thinning disorder that can lead to vision loss. In the last 2 decades, corneal crosslinking (CXL) has emerged as an effective method to halt the progression of keratoconus and reduce the number of patients requiring keratoplasty. The procedure has been adopted globally and has evolved to become a part of combination treatments to regularize the cornea and improve visual outcomes. CXL has even been extrapolated in managing other ocular pathologies such as progressive myopia, infectious keratitis, and bullous keratopathy. This review aims to summarize the current role of CXL in keratoconus and its alternative uses, and provide insights into future developments in this fast-developing field.

Fresh Human Myopic Lenticule Intrastromal Implantation for Keratoconus Using SMILE Surgery in a Long-term Follow-up Study: Ultrastructural Analysis by Transmission Electron Microscopy.

PURPOSE: To investigate new intrastromal histological structures that develop after myopic human lenticular implantation in keratoconus with femtosecond laser-assisted small incision lenticule extraction (SMILE) surgery using transmission electron microscopy. METHODS: Sixty eyes with advanced keratoconus indicated for corneal transplantation were included in this study. Fresh myopic lenticular implants were placed in all eyes through SMILE surgery. Lenticular implants were extracted from patients with myopic refractive errors of the cornea, untreated keratoconus, and treated keratoconus following 1, 2, and 3 years of surgery. These five lenticular samples were examined under the electron microscope and compared. RESULTS: Disorganized and thinned collagen fibers were observed in the stroma with degenerative stromal cells (telocyte-like cells and keratocytes) in the keratoconic cornea. Apoptotic bodies and cell debris were easily observed near the disorganized fibers. In contrast, the myopic refractive error of the control and treatment groups demonstrated well-organized parallel lamellar structures. Healthy keratocytes and telocyte-like cells were observed in samples obtained 1, 2, and 3 years after lenticular implantation. Thus, telocyte-like cells may be activated by appropriate stimuli, such as stem cells, and be involved in stromal regeneration. CONCLUSIONS: Fresh myopic intrastromal lenticular implantation is a safe, economical, and reliable technique that leads to increased corneal thickness, improved visual acuity, and the regeneration of healthy keratocytes and telocyte-like cells that are involved in stromal regeneration. [J Refract Surg. 2022;38(8):520-528.].

Late onset of a persistent, deep stromal and endothelial scarring after corneal collagen crosslinking for keratoconus: A case report.

INTRODUCTION: To report a late onset, deep stromal and endothelial corneal scar in a keratoconus patient after corneal collagen cross-linking (CXL). CASE DESCRIPTION: Observational case report. A 29-year-old man with bilateral keratoconus received an accelerated (A-CXL 10*9) epithelium-off CXL procedure in the left eye.6-months postoperatively, a 2.2 × 1.2 mm inferocentral corneal scar was detected, which was located in the posterior stroma ranging from approximately 350 µm until the endothelium, therefore was situated below the demarcation line. A topical corticosteroid treatment did not influence the magnitude or configuration of the scar. Visual acuity was never affected, which includes the examination 12 months postoperatively. CONCLUSIONS: We report a case of a late onset deep stromal and endothelial corneal scar 6 months after accelerated CXL as postoperative complication without affecting visual acuity.

Ruthenium-induced corneal collagen crosslinking under visible light.

Corneal collagen crosslinking (CXL) is a commonly used minimally invasive surgical technique to prevent the progression of corneal ectasias, such as keratoconus. Unfortunately, riboflavin/UV-A light-based CXL procedures have not been successfully applied to all patients, and result in frequent complications, such as corneal haze and endothelial damage. We propose a new method for corneal crosslinking by using a Ruthenium (Ru) based water-soluble photoinitiator and visible light (430 nm). Tris(bipyridine)ruthenium(II) ([Ru(bpy)3]2+) and sodium persulfate (SPS) mixture covalently crosslinks free tyrosine, histidine, and lysine groups under visible light (400-450 nm), which prevents UV-A light-induced cytotoxicity in an efficient and time saving collagen crosslinking procedure. In this study, we investigated the effects of the Ru/visible blue light procedure on the viability and toxicity of human corneal epithelium, limbal, and stromal cells. Then bovine corneas crosslinked with ruthenium mixture and visible light were characterized, and their biomechanical properties were compared with the customized riboflavin/UV-A crosslinking approach in the clinics. Crosslinked corneas with a ruthenium-based CXL approach showed significantly higher young's modulus compared to riboflavin/UV-A light-based method applied to corneas. In addition, crosslinked corneas with both methods were characterized to evaluate the hydrodynamic behavior, optical transparency, and enzymatic resistance. In all biomechanical, biochemical, and optical tests used here, corneas that were crosslinked with ruthenium-based approach demonstrated better results than that of corneas crosslinked with riboflavin/ UV-A. This study is promising to be translated into a non-surgical therapy for all ectatic corneal pathologies as a result of mild conditions introduced here with visible light exposure and a nontoxic ruthenium-based photoinitiator to the cornea. STATEMENT OF SIGNIFICANCE: Keratoconus, one of the most frequent corneal diseases, could be treated with riboflavin and ultraviolet light-based photo-crosslinking application to the cornea of the patients. Unfortunately, this method has irreversible side effects and cannot be applied to all keratoconus patients. In this study, we exploited the photoactivation behavior of an organoruthenium compound to achieve corneal crosslinking. Ruthenium-based organic complex under visible light demonstrated significantly better biocompatibility and superior biomechanical results than riboflavin and ultraviolet light application. This study promises to translate into a new fast, efficient non-surgical therapy option for all ectatic corneal pathologies.

Evaluation of Corneal Biomechanical Indices in Distinguishing Between Normal, Very Asymmetric, and Bilateral Keratoconic Eyes.

PURPOSE: To evaluate the ability of biomechanical indices provided by the Ocular Response Analyzer (ORA; Reichert Ophthalmic Instruments) and dynamic Scheimpflug analyzer (Corvis ST; Oculus Optikgeräte GmbH) to distinguish between normal eyes and eyes with very asymmetric ectasia (VAE) and mild and moderate keratoconus. METHODS: This prospective, observational, and monocentric study included normal eyes (defined as keratoconus percentage index < 60, Belin/Ambrósio total deviation value [BAD-D] < 1.6, inferior-superior keratometry [I-S value] < 1.45 and maximum keratometry [Kmax] < 47) and eyes with clinical bilateral keratoconus (mild and moderate) and VAE (defined as unilateral keratoconus, where one eye showed a clinical keratoconus and the fellow eye was topographically normal [VAE-NT] or topographically and tomographically normal [VAE-NTT]). All eyes were measured by the Pentacam (Oculus Optikgeräte GmbH), ORA, and Corvis ST. Receiver operating characteristic curve analysis was performed to test the diagnostic ability. RESULTS: Fifty-eight normal eyes and 238 ectatic eyes were included. The highest area under the curve (AUC) was provided by the Corvis Biomechanical Index (CBI) with an AUC of 0.979, followed by ORA corneal resistance factor (0.865), and corneal hysteresis (0.824) separating normal eyes from all ectatic subgroups. The AUC of the CBI was statistically significantly higher than all other parameters (DeLong test, P < .001). A sensitivity of 100% and 70.9%, respectively, and a specificity of 93.1% was found to distinguish normal eyes from VAE-NT and VAE-NTT using a cut-off value of 0.2. CONCLUSIONS: The assessment of biomechanical properties is an additional important method to evaluate corneal ectasia independent of its stage. The CBI provides further information for ectasia screening in cases where corneal topography and tomography are clinically not suspicious by using a cutoff of 0.2. [J Refract Surg. 2022;38(6):364-372.].

Use of a Single Radial Incision to Improve Curvature Matching and Graft Adhesion in Descemet Membrane Endothelial Keratoplasty in a Patient With Keratoconus.

PURPOSE: The purpose of this study was to report a novel surgical technique for altering donor Descemet membrane endothelial keratoplasty (DMEK) curvature to match host posterior stroma in a patient with advanced keratoconus (KC) and endothelial decompensation. METHODS: We report a 56-year-old man with Fuch endothelial dystrophy and KC, who underwent DMEK due to endothelial decompensation. A triangular area of graft detachment centered on the apex of cones persisted after repeat gas tamponade. A radial incision from the graft edge to the apex was used to allow overlapping of the graft, thereby increasing the grafts curvature. RESULTS: The use of a radial incision in the Descemet membrane (DM) graft was made to allow the graft overlap and adapt to the new shape. By matching the donor curvature to that of the hosts posterior curvature, full adhesion of the graft was achieved with the use of a short-acting air bubble by 1 week after the procedure. CONCLUSIONS: The mismatch in the curvature of the DM graft and the host posterior corneal surface, in cases with KC or very steep corneas, should be taken into consideration because it can lead to redundancy folds. These can result in atypical, conical detachments, distinct from the typical peripheral detachments seem commonly in DMEK. A single radial incision in the DM graft combined with air tamponade is a feasible treatment option in cases where DMEK fails to attach because of apparent curvature mismatch between the donor and host.

Pathogenesis of keratoconus: NRF2-antioxidant, extracellular matrix and cellular dysfunctions.

Keratoconus (KC) is a degenerative disease associated with cell and extracellular matrix (ECM) loss that causes gradual thinning and steepening of the cornea and loss of vision. Collagen cross linking with ultraviolet light treatment can strengthen the ECM and delay weakening of the cornea, but severe cases require corneal transplantation. KC is multifactorial and multigenic, but its pathophysiology is still an enigma. Multiple approaches are being pursued to elucidate the molecular changes that underlie the corneal phenotype to identify relevant genes for tailored candidate searches and to develop potential biomarkers and targets for therapeutic interventions. Recent proteomic and transcriptomic studies suggest dysregulations in oxidative stress, NRF2-regulated antioxidant programs, WNT-signaling, TGF-ß, ECM and matrix metalloproteinases. This review aims to provide a broad update on the transcriptomic and proteomic studies of KC with a focus on findings that relate to oxidative stress, and dysregulations in cellular and extracellular matrix functions.

Repeatability and Comparison of Corneal Tomography in Mild to Severe Keratoconus Between the Anterior Segment OCT MS-39 and Pentacam HR.

PURPOSE: To detect keratoconus progression, accuracy of tomographic measurements is crucial. The impoved axial resolution of optical coherence tomography (OCT) compared to Scheimpflug photography serves as the motivation to investigate and compare the repeatability of the anterior segment OCT MS-39 (CSO) to Pentacam HR (Oculus Optikgeräte GmbH) in patients with keratoconus. METHODS: One hundred twenty-three eyes of 123 patients with keratoconus were enrolled and subdivided in four groups by maximum keratometry (Kmax): Kmax < 48.00 diopters (D), Kmax of 48.00 to 53.01 D, Kmax of 53.00 to 58.00 D, and Kmax > 58.00 D. Three consecutive measurements per eye were acquired with the MS-39 and compared to the Pentacam HR. Kmax, thinnest pachymetry, anterior asphericity, and posterior elevation data were compared. Within-subject standard deviation (Sw), coefficient of variation (CoV), test-retest repeatability (TRT), and the intra-class correlation (ICC) were calculated and evaluated. Bland-Altman plots were also analyzed. RESULTS: The Pentacam HR measures significantly higher Kmax values than the MS-39, with a more pronounced difference for severe cases of keratoconus (0.57 D for all cases; 1.88 D for cases with Kmax > 58.00 D). Thinnest pachymetry was approximately 5 µm thinner when measured by the Pentacam HR than the MS-39, independently of keratoconus stage. A further progressed keratoconus stage was significantly associated with increased measurement errors and resulted in worse repeatability (Kmax < 48.00 D: Sw = 0.18 D, TRT = 0.50 D, CoV = 0.39%, ICC = 0.989; Kmax > 58.00 D: Sw = 0.53 D, TRT = 1.48 D, CoV = 0.90%, ICC = 0.984). The behavior was similar for other tomographic parameters. CONCLUSIONS: The Pentacam HR and the MS-39 have an overall good agreement for keratoconus; however, the Pentacam HR measures steeper and thinner than the MS-39. The association between the magnitude of topographic and tomographic parameters and their measurement errors suggests that the diagnosis of keratoconus disease progression should be based on the stage and the test-retest repeatability rather than on a fixed value (eg, 1.00 D). [J Refract Surg. 2022;38(4):250-255.].

Management of Late Descemet's Membrane Detachment After Penetrating Keratoplasty in Keratoconus.

PURPOSE: The purpose of this study was to describe the feasibility of Descemet membrane endothelial keratoplasty (DMEK) as a treatment modality for spontaneous detachment of DM (DMD) decades after penetrating keratoplasty (PK) for keratoconus. METHODS: We describe the clinical characteristics and therapeutic surgical approach in 6 eyes of 5 patients with DMD. Clinical images, anterior segment optical coherence tomography scans, and histological findings are presented. RESULTS: Mean age of patients at time of diagnosis was 60 years (range 56-66 years). Mean interval between PK and occurrence of DM detachment was 36 years (range 29-45 years). In 4 of 6 eyes, air injections into the anterior chamber were initially attempted to reattach DM to the stroma but without long-lasting effect. Two eyes underwent repeat PK because of pronounced ectasia after long-standing DMD and stromal scars. DMEK was performed successfully in 4 eyes leading to an increase in visual acuity and a reduction in central corneal thickness. Electron microscopy showed abnormal vacuolar inclusions and collagenous material in the posterior nonbanded layer and a separation of the anterior banded layer from the posterior nonbanded layer. CONCLUSIONS: This case series provides evidence that DMEK is a viable option in eyes with spontaneous DM detachment after PK. Visual outcome is limited by the persisting high astigmatism in the ectatic cornea. Illustrated by a small series of patients, the results of DMEK in this condition are presented and new findings about the pathophysiology are given.