Corneal Alterations Research Articles

Chemotherapy Induced Corneal Changes Assessed by Corneal Confocal Microscopy: A Review.

The eye, and the cornea in particular, is a common site of chemotherapy induced toxicity, and ocular side effects of both traditional and novel agents have been reported. Corneal confocal microscopy (CCM) is an in vivo technique that allows for the study of all the corneal layers in an easy, non-invasive and reproducible way via the direct visualization of corneal cell morphologies as well as of sub-basal nerve plexus. Thus, it represents a useful way to identify and monitor chemotherapy induced corneal alterations. This work aims to review the use of CCM in identifying corneal toxicity secondary to chemotherapy treatment, as regards both corneal nerves alterations in the setting of chemotherapy induced peripheral neuropathy (CIPN) and other corneal structure changes, particularly involving the corneal epithelium.

Changes and Influencing Factors of Corneal Endothelial Cells and Central Corneal Thickness after Pediatric Cataract Surgery

Introduction: This study aimed to examine the impact of cataract surgery on the corneal endothelium and central corneal thickness (CCT) in pediatric patients, and to identify the factors associated with corneal alterations. Methods: This retrospective study included consecutive children undergoing bilateral or unilateral cataract surgery and intraocular lens implantation at the Eye Hospital of Wenzhou Medical University, with or without posterior capsulorhexis and anterior vitrectomy, and an age-matched normal control group. This study aimed to assess whether changes in corneal parameters, including CCT, corneal endothelial cell density (CD), average cell area (AVE), standard deviation of size (SD), coefficient of variation (CV), percentage of hexagonal cells (6A) before and after surgery, and endothelial cell loss (ECL) differed among the bilateral cataract, unilateral cataract, and control groups. Furthermore, the potential effects of anterior vitrectomy, axial length, preoperative anterior chamber depth, surgical duration, horizontal corneal diameter, intraoperative pupil diameter (PD), and the number of corneal sutures on corneal endothelial parameters and CCT were investigated. Results: A total of 107 eyes from 107 children were included in the study. In the bilateral cataract group, CD significantly decreased, AVE and CCT significantly increased, and ECL was significantly higher than in the control group. The unilateral cataract group also exhibited a significant increase in CCT. Additionally, the number of corneal sutures was negatively correlated with CD, and PD was negatively correlated with CV in the unilateral cataract group. Conclusion: Cataract surgery in pediatric patients results in increased CCT, reduced CD, and morphological changes in corneal cells. A greater number of corneal sutures and a smaller PD increased the risk of CD reduction and elevated CV in the unilateral cataract group, underscoring the need for ophthalmologists to minimize corneal damage in these children.

Quantitative assessment of corneal biomechanical changes in vivo after photorefractive intrastromal corneal cross-linking using optical coherence elastography.

Photorefractive intrastromal corneal cross-linking (PiXL) treatment corrects myopia by enhancing localized central corneal biomechanics. However, the dose-effect relationship between the changes in corneal biomechanics and alterations in corneal curvature resulting from this treatment remain unclear. We therefore developed an acoustic radiation force optical coherence elastography (ARF-OCE) technique to investigate the dose-effect relationship in PiXL. ARF-OCE measurements and corneal topography were performed 3 days before and 1 week after PiXL treatment. Depth-resolved Young's modulus images of the in vivo corneas were obtained based on the phase velocity of the Lamb wave. PiXL treatments with five ultraviolet-A (UVA) energy doses (5.4, 15, 25, 35, and 45 J/cm2) were administered to rabbit corneas in vivo (n=15). The percentage change in Young's modulus (ΔE%) of the cornea increased from 0.26 to 1.71 as the UVA energy dose increased from group I (5.4 J/cm2) to group V (45 J/cm2). Meanwhile, the change in the mean keratometry (ΔKm ) of the cornea increased from 0.40 to 2.10 diopters (D) as the UVA energy dose increased from group I to group IV (35 J/cm2). Furthermore, a statistically significant positive correlation was observed between ΔE% and ΔKm in groups I to IV. With increasing UVA energy dose, the corneal Young's modulus significantly increased. Given the observed correlation, ΔE% holds promise as a new quantitative biomechanical parameter for determining the dose-effect relationship in PiXL treatment. It should be emphasized that there may be an inflection point of ΔE%, at which corneal keratometry ceases to flatten and begins to increase. The ARF-OCE system has demonstrated its efficacy in quantitatively assessing changes in corneal biomechanics in vivo following PiXL treatment. This technique has great potential in facilitating the quantitative determination of the dose-effect relationship in PiXL treatment.

Reticulated Retinoic Acid Synthesis is Implicated in the Pathogenesis of Dry Eye in Aqp5 Deficiency Mice.

Abnormalities in aquaporins are implicated in the pathological progression of dry eye syndrome. Retinoic acid (RA) regulates cellular proliferation, differentiation, and apoptosis in the cornea, thereby being associated with dry eye disease (DED). The objective of this study is to explore the underlying mechanisms responsible for RA metabolic abnormalities in corneas lacking aquaporin 5 (AQP5). Dry eye (DE) models were induced via subcutaneous scopolamine hydrobromide. Aqp5 knockout (Aqp5-/-) mice and DE mice were utilized to assess corneal epithelial alterations. Tear secretion, goblet cell counts, and corneal punctate defects were evaluated. The impact of Aqp5 on RA-related enzymes and receptors was investigated using pharmacological RA or SR (A JunB inhibitor), a transcription factor JunB inhibitor, treatment in mouse corneal epithelial cells (CECs), or human corneal epithelial cells (HCECs). The HCECs and NaCl-treated HCECs underwent quantitative real-time PCR (qRT-PCR), immunofluorescent, Western blot, and TUNEL assays. The regulation of transcription factor JunB on Aldh1a1 was explored via ChIP-PCR. Aqp5 and Aldh1a1 were reduced in both CECs of DE mice and NaCl-induced HCECs. Aqp5-/- mice exhibited DE phenotype and reduced Aldh1a1. RA treatment reduced apoptosis, promoted proliferation, and improved the DE phenotype in Aqp5-/- mice. JunB enrichment in the Aldh1a1 promoter was identified by ChIP-PCR. SR significantly increased Aldh1a1 expression, Ki67, and ΔNp63-positive cells, and decreased TUNEL-positive cells in CECs and HCECs. Our findings demonstrated the downregulation of Aqp5 expression and aberrant RA metabolism in DE conditions. Knockout of Aqp5 resulted in reduced production of RA through activation of JunB, subsequently leading to the manifestation of DE symptoms.

Blepharoptosis and corneal epithelial thickness alterations, is there any relation?

BackgroundTo compare the epithelial thickness map of ptotic eyes of blepharoptosis patients with contralateral non- ptotic eyes.MethodsUnilateral blepharoptosis patients were enrolled consecutively. Patients were underwent full ophthalmologic examination and their demographic data such as age and gender and specific ptosis findings e.g. the cause and duration, MRD-1, and levator palpebralis superioris function were registered. Anterior segment imaging for epithelial thickness measurements was done using the Avanti RTVue-XR platform. The corneal epithelial thickness maps of ptotic and non-ptotic eyes were compared.Results44 patients with unilateral blepharoptosis were included in the study. 27 (61.4%) of them were female and 17 (38.6%) cases were male. The mean of the patients’ ages was 24.40 ± 15.16 years. Ptotic eyes had significantly thinner superior (p = 0.000), superior-temporal (p = 0.000) and superior-nasal (p = 0.005) sectors of the cornea and slightly thicker corneal epithelium (CE) in the inferior-nasal sector. The correlation of difference of superior-inferior CE was evaluated with different parameters including patient’s age (p = 0.457), type of blepharoptosis (p = 0.786), duration of blepharoptosis (p = 0.477) and MRD1 (p = 0.248), but no correlation was found.ConclusionsThis study revealed that lid position in blepharoptosis may have effects on the corneal epithelial thickness map. Because of the lower position of upper eyelid, a thinning effect on superior corneal sectors may happen.

The Severity of Diabetic Retinopathy Corresponds with Corneal Nerve Alterations and Ocular Discomfort of the Patient.

Diabetic retinopathy (DR) remains the leading cause of blindness in the working-age population. Its progression causes gradual damage to corneal nerves, resulting in decreased corneal sensitivity (CS) and disruption of anterior-eye-surface homeostasis, which is clinically manifested by increased ocular discomfort and dry eye disease (DED). This study included 52 DR patients and 52 sex- and age-matched controls. Ocular Surface Disease Index (OSDI) survey, tear film-related parameters, CS, and in vivo corneal confocal microscopy (IVCM) of the subbasal plexus were performed. Furthermore, all patients underwent tear sampling for neurotrophin and cytokine analysis. OSDI scores were greater in DR patients than in controls (p = 0.00020). No differences in the Schirmer test score, noninvasive tear film-break-up time (NIBUT), tear meniscus or interferometry values, bulbar redness, severity of blepharitis or meibomian gland loss were found. In the DR group, both the CS (p < 0.001), and the scotopic pupil diameter (p = 0.00008) decreased. IVCM revealed reduced corneal nerve parameters in DR patients. The stage of DR was positively correlated with the OSDI (Rs = +0.51, 95% CI: + 0.35-+0.64, p < 0.001) and negatively correlated with IVCM corneal nerve parameters and scotopic pupillometry (Rs = -0.26, 95% CI: -0.44--0.06, p = 0.0097). We found negative correlations between the OSDI and IVCM corneal innervation parameters. The DR group showed lower tear film-brain-derived neurotrophic factor (BDNF) levels (p = 0.0001) and no differences in nerve growth factor (NGF)-β, neurotrophin (NT)-4, vascular endothelial growth factor (VEGF), interleukin (IL)-1β, IL-4, IL-5, IL-6, or IL-12 concentrations. Tumor necrosis factor (TNF)-α, IL-2, IL-8, IL-10, granulocyte macrophage colony-stimulating factor (GM-CSF), and interferon (IFN)-γ levels were decreased among patients with DR. Corneal innervation defects have a direct impact on patients' subjective feelings. The evolution of DR appears to be associated with corneal nerve alterations, emphasizing the importance of IVCM.

Endothelial Involvement in Monocular Mpox Keratitis: In Vivo Confocal Microscopy Approach.

The aim of this study was to describe the clinical features and endothelial involvement in a case of Mpox virus keratitis by in vivo confocal microscopy (IVCM). This is a case report. A 35-year-old man presented with redness, photophobia, pain, tearing, and a low visual acuity of 0.09 (decimal) in the left eye with a 6-week history of Mpox and corneal trauma. Previous testing of blood, interdigital skin lesions, and conjunctival and eyelid margin swabs confirmed the presence of Mpox by polymerase chain reaction. Biomicroscopy displayed superficial stromal infiltrates with a continuous but irregular epithelium. IVCM revealed the presence of pseudoguttata, loss of defined cell boundaries, infiltration of inflammatory cells in the endothelial layer, endothelial ridges, and precipitated pigmented granules, consistent with endotheliitis. After this episode, the patient had 4 reactivations, also treated with topical corticoids and oral tecovirimat 600 mg twice a day for 2 weeks. On the fourth reactivation, this treatment was extended to 4 weeks. On the last visit, the patient presented a visual acuity of 0.5 with disciform keratitis and reduced endotheliitis signs. The endothelial cell density remained normal during the follow-up (2763 ± 376 cell/mm 2 at baseline and 2795 ± 238 cell/mm 2 at the last visit). Polymegathism and pleomorphism showed altered values during the follow-up. Patients with an altered corneal epithelial barrier could suffer Mpox endotheliitis, like other DNA viruses, before disciform keratitis appears. IVCM is a useful tool for the early detection of endotheliitis and for describing its evolution, improving patient care.

Clinical assessment of corneal alterations in endocrine disorders

Corneal alterations are frequent in many endocrine disorders like Grave’s ophthalmopathy and diabetes mellitus. Since early diagnosis of such a change can prevent visual impairment, it presents a challenge to an ophthalmologist.Clinical assessment &amp; significance of corneal alterations in endocrine disorders.1. To conduct comprehensive assessment of corneal alterations in endocrine disorders. 2. To Identify specific corneal abnormalities in patients with endocrine disorders. 3. To delineate the clinical significance of corneal alterations in endocrine disorders by determining their impact on visual function and guiding therapeutic strategies.This study was a prospective, observational, hospital-based study conducted over a period of two years including 150 patients of different endocrine disorders. Ocular examination included physical examination to check for any pain on ocular movements, ophthalmoplegia, diplopia, or proptosis. Visual acuity was examined by Snellen’s chart, anterior segment by slit-lamp, intra-ocular pressure by non-contact tonometer, qualitative measurement of corneal sensation by a cotton-wisp and central corneal thickness was measured by pachymetry. Corneal endothelial cell parameters like endothelial cell density (ECD), coefficient of variation of cell area (CV), percentage of hexagonal cell (HEX) were measured by clinical specular microscope.The age range was 14 to 82 years with mean age being 48.43±14.2 years. The male to female ratio was 1.34:1. Type-2 diabetes mellitus was the most frequently encountered endocrine disorder (64.7%), followed by hypothyroidism (13.3%). Addison’s disease was the least encountered (0.7%). The most severe changes to the cornea, such as chronic epithelial abnormalities, superficial punctate keratopathy, altered corneal sensations, and dry eyes, were observed in patients with type 2 diabetes, followed by Graves’s ophthalmopathy and hypothyroidism. Patients with T2DM and T1DM had elevated CCT values, reduced endothelial cell density, abnormally high coefficient of variance and low hexagonal cells.The present study showed that different corneal alterations can be possible in endocrine disorders. So all endocrine disorders should undergo comprehensive ophthalmological examination to prevent visual impairment.

Corneal reinnervation in patients with severe neurotrophic keratopathy secondary to herpes zoster ophthalmicus after treatment with autologous serum tear drops.

To study potential corneal reinnervation and recovery of corneal sensation in patients with severe neurotrophic keratopathy (NK) secondary to herpes zoster ophthalmicus (HZO) after treatment with topical autologous serum tears (AST). Four cases of HZO with severe NK were followed clinically and by serial laser in vivo confocal microscopy (IVCM, HRT3/RCM, Heidelberg Engineering) before and during treatment with 20% AST drops eight times a day. Two masked observers reviewed the IVCM images and assessed corneal nerve alterations. At baseline, all patients had complete loss of corneal sensation. In addition, IVCM showed complete lack of the subbasal corneal nerve plexus in all patients. All four patients were refractory to conventional therapies and were treated with AST drops. All patients demonstrated significant nerve regeneration by IVCM within 3-7 months of treatment. The total nerve density increased to a mean ± SEM of 10,085.88±2,542.74 μm/mm2 at the last follow up. Corneal sensation measured by Cochet-Bonnet esthesiometry improved to a mean ± SEM of 3.50±1.30 cm. Interestingly, 3 of 4 patients developed stromal keratitis with ulceration within weeks of corneal reinnervation, which was reversed by adding topical steroids. Autologous serum tears are effective in restoring corneal subbasal nerves and sensation in patients with severe NK secondary to HZO. However, this group of patients may require concurrent topical immunomodulation and antiviral therapy while on AST to prevent stromal keratitis.

Diabetic corneal neuropathy and its relation to the severity of retinopathy in patients with type 2 diabetes mellitus: an in vivo confocal microscopy study.

To investigate corneal neuropathy and corneal nerve alterations in type 2 diabetes mellitus (DM) patients with different diabetic retinopathy (DR) status. A total of 87 eyes of 87 patients with DM and 28 eyes of 28 healthy control subjects were included in the study. DM patients were further classified into 3 groups: patients without DR (NDR), patients with non-proliferative DR (NPDR), and patients with proliferative DR (PDR). PDR patients were classified into 2 groups regarding having undergone retinal argon laser photocoagulation treatment (ALP). Ocular surface disease index score (OSDI), average tear break-up time (A-BUT), corneal sensitivity and cornea nerve fiber length (CNFL), cornea nerve fiber density (CNFD), and cornea nerve branch density (CNBD) of the cornea subbasal nerve plexus (SBNP) were measured using in vivo confocal microscopy (IVCM). OSDI scores increased and A-BUT decreased in DM patients compared to the control group, but no significant difference was found between DM patient groups. Corneal sensitivity decreased in DM patients who developed DR, compared to both the controls and the NDR group. CNFD and CNFL decreased in NPDR and PDR patients compared to controls. CNFD and CNBD decreased in patients who had developed PDR, compared to all three groups. All IVCM parameters decreased with DR progression. IVCM can detect early structural corneal nerve changes in diabetic patients. The presence of DM affects ocular surface parameters, especially in long-term DM patients. Corneal sensitivity loss is increased with the presence of DR. All IVCM parameters decrease with DR development and its progression.

Diabetic Keratopathy: Redox Signaling Pathways and Therapeutic Prospects.

Diabetes mellitus, the most prevalent endocrine disorder, not only impacts the retina but also significantly involves the ocular surface. Diabetes contributes to the development of dry eye disease and induces morphological and functional corneal alterations, particularly affecting nerves and epithelial cells. These changes manifest as epithelial defects, reduced sensitivity, and delayed wound healing, collectively encapsulated in the context of diabetic keratopathy. In advanced stages of this condition, the progression to corneal ulcers and scarring further unfolds, eventually leading to corneal opacities. This critical complication hampers vision and carries the potential for irreversible visual loss. The primary objective of this review article is to offer a comprehensive overview of the pathomechanisms underlying diabetic keratopathy. Emphasis is placed on exploring the redox molecular pathways responsible for the aberrant structural changes observed in the cornea and tear film during diabetes. Additionally, we provide insights into the latest experimental findings concerning potential treatments targeting oxidative stress. This endeavor aims to enhance our understanding of the intricate interplay between diabetes and ocular complications, offering valuable perspectives for future therapeutic interventions.

Detecting Keratoconus in Adolescents with Anterior Segment Optical Coherence Tomography.

Assessing the applicability of an algorithm developed for keratoconus detection in adolescents. This algorithm relies on optical coherence tomography (OCT) and incorporates features related to corneal pachymetric and epithelial thickness alterations. We retrospectively reviewed charts of patients under the age of 18 and divided them into four groups according to the Belin-Ambrosio display (Pentacam): normal, manifest, and subclinical keratoconus, as well as very asymmetric eye with normal topography and tomography (VAE-NTT). Corneal and epithelial thickness maps (Cirrus 5000 HD-OCT, Carl Zeiss Meditec, Germany) were evaluated by a human grader. In the first step, if at least one of four parameters (pachymetry minimum (pachy min), pachy minimum-median (min-med), pachy superonasal-inferotemporal (SN-IT), or epithelial (epi SN-IT)) exceeded its cut-off value, the eye was considered as suspect. In the second step, the combined presence of coincident thinning of total cornea and epithelium as well as concentric epithelial thinning lead to the diagnosis of keratoconus. Receiver operating characteristic (ROC) curves were generated to determine area under the curve (AUC), sensitivity, and specificity for the parameters. The study involved 19 pediatric patients diagnosed with keratoconus, comprising 29 manifest keratoconic eyes, 3 eyes with subclinical keratoconus, and 5 VAE-NTT eyes. In addition, 22 eyes from 11 normal adolescents were included in the analysis. The AUC values of parameters in step 1 were 0.889 for pachy min, 0.997 for pachy min-med, 0.893 for pachy SN-IT, and 0.998 for epi SN-IT. When both steps were performed, this algorithm captured all manifest and subclinical pediatric keratoconic eyes. When all eyes of the keratoconus patients were combined, step 1 had 97.3% sensitivity and step 2 had 100% specificity. Using this OCT-based approach in adolescents yielded a high level of agreement with the current gold standard, tomography. Using them together, potentially also with other examinations may improve the diagnostic accuracy of KC in the pediatric population. Integration of this approach into the software of the device to facilitate automated evaluations is desired.

Sterile donor tomography for improvement of refractive results after keratoplasty

Purpose: Any corneal microsurgeon may have inadvertently transplanted a donor corneal tissue with (subclinical) keratoconus or prior keratorefractive surgery, which typically leads to postoperative refractive surprises and cannot always be detected in the eye bank with only slit lamp. Given the increased number of keratorefractive procedures performed in the last decades, eye banks will soon have to face this problem more intensively. Thus, the efficiency and reliability of anterior segment optical coherence tomography (AS‐OCT) as a non‐invasive and sterile screening method in the eye bank to detect corneal grafts with curvature and/or thickness abnormalities was assessed.Methods: 1315 donor corneal tissues mounted in sterile tissue cultivation flasks were imaged using an AS‐OCT. The corneal tissues were preserved in organ culture medium I and transferred into organ culture medium II (containing dextran T‐500 6%) for deswelling at least 24 h prior to measurement and keratoplasty. Depth raster scans were performed through the posterior surface of the corneal tissues within a 7 mm central zone to create 3D volume data. The volume data set was preprocessed to eliminate flask reflections artefacts and to define the region of interest (ROI). Subsequently, the adaptation of a sphero‐cylindrical surface model was carried out with raytracing. Thus, the radii of curvature for the front and back surfaces can be determined and a corneal thickness map is generated.Results: The mean steep/flat front surface radius was 7.46 ± 0.29 (5.07–9.29)/7.69 ± 0.24 (6.70–9.50) mm, the corresponding values for the back surface being 6.47 ± 0.32 (5.00–8.00)/6.80 ± 0.31 (5.81–8.00) mm and the mean central thickness was 610 ± 84 (379–1457) μm. Abnormalities (beyond ±2 or ± 3 SD) were found in 140 or 34 corneas (10.6% or 2.6%) for anterior surface curvature, 120 or 38 corneas (9.1% or 2.9%) for the posterior surface, and 55 or 16 corneas (4.2% or 1.2%) for thickness.Conclusions: The AS‐OCT provides an objective, sterile and semi‐automated screening method to identify corneal morphological and refractive alterations (e.g. keratoconus, status post PRK/LASIK) and further optimize corneal donor selection in the eye bank. Corneal donors with curvature or thickness abnormalities ±3 SD do not have to be discarded but can be used for posterior lamellar keratoplasty or tectonic keratoplasty.

Corneal structural alterations in autism spectrum disorder: An in vivo confocal microscopy study.

Individuals with autism spectrum disorder (ASD) often exhibit joint hypermobility and connective tissue disorders. However, it remains unclear if ASD individuals also have structural alterations in the connective tissue of the cornea. This study aims to determine whether the Kobayashi structure (K-structure) characteristics differ between adults with ASD and typically developing controls (TDC) and explore the clinical correlates of the K-structure abnormality. We recruited 30 ASD adults and 35 TDC. Corneal structures, particularly the K-structure in the Bowman's layer, of the participants were examined using in vivo confocal microscopy (IVCM), and a K-grading ranging from 1 to 4 was given to each eye based on the level of morphological mosaicism. The ASD participants' eyes received a significantly higher single-eye K-grading than that of the TDC eyes (p < 0.001), and the medians [25th, 75th percentile] of bilateral-eye summed K-grading were 8 [7, 8] and 5 [4, 6] in ASD and TDC, respectively (p < 0.001). A significantly higher K-grading in the ASD participants' eyes was still observed after adjusting for the within-subject inter-eye correlation (p < 0.001). Youden Index showed the optimal cutoffs to differentiate ASD from TDC by bilateral-eye summed K-grading and single-eye K-grading was >6 and >3, respectively. Additionally, a higher K-grading was associated with fewer visual sensation seeking in ASD (Spearman's correlation coefficient ρ = -0.518, p = 0.008) and low visual registration (i.e., higher sensory threshold) in TDC (ρ = 0.446, p = 0.023). This study provided novel evidence of corneal structural alterations in ASD by IVCM. Our findings may not only support the prior hypothesis of the association between ASD and connective tissue abnormalities but also shed light on the relationship between connective tissue disorder and neurodevelopmental disorders.

Localized Corneal Biomechanical Alteration Detected In Early Keratoconus Based on Corneal Deformation Using Artificial Intelligence.

This study aimed to develop a novel method to diagnose early keratoconus by detecting localized corneal biomechanical changes based on dynamic deformation videos using machine learning. Diagnostic research study. We included 917 corneal videos from the Tianjin Eye Hospital (Tianjin, China) and Shanxi Eye Hospital (Xi'an, China) from February 6, 2015, to August 25, 2022. Scheimpflug technology was used to obtain dynamic deformation videos under forced puffs of air. Fourteen new pixel-level biomechanical parameters were calculated based on a spline curve equation fitting by 115,200-pixel points from the corneal contour extracted from videos to characterize localized biomechanics. An ensemble learning model was developed, external validation was performed, and the diagnostic performance was compared with that of existing clinical diagnostic indices. The performance of the developed machine learning model was evaluated using precision, recall, F1 score, and the area under the receiver operating characteristic curve. The ensemble learning model successfully diagnosed early keratoconus (area under the curve = 0.9997) with 95.73% precision, 95.61% recall, and 95.50% F1 score in the sample set (n=802). External validation on an independent dataset (n=115) achieved 91.38% precision, 92.11% recall, and 91.18% F1 score. Diagnostic accuracy was significantly better than that of existing clinical diagnostic indices (from 86.28% to 93.36%, all P <0.01). Localized corneal biomechanical changes detected using dynamic deformation videos combined with machine learning algorithms were useful for diagnosing early keratoconus. Focusing on localized biomechanical changes may guide ophthalmologists, aiding the timely diagnosis of early keratoconus and benefiting the patient's vision.

Impact of Age on the Characteristics of Corneal Nerves and Corneal Epithelial Cells in Healthy Adults.

The aim of this study was to investigate age-related changes in corneal nerves and corneal epithelial cell parameters and to establish age-adjusted reference values. A total of 7025 corneal nerve images and 4215 corneal epithelial images obtained using in vivo confocal microscopy from 281 eyes of 143 healthy participants were included. Seven corneal nerve parameters and 3 corneal epithelial cell parameters were quantified using 2 automatic analytic software and analyzed across 6 age groups ranging from 21 to 80 years. There was a declining trend in all 7 nerve parameters with advancing age. In particular, corneal nerve fiber length and corneal nerve fiber density demonstrated a significant decrease in subjects aged 65 years or older compared with subjects younger than 65 years (10.8 ± 2.6 mm/mm 2 vs. 9.9 ± 2.0 mm/mm 2 , P = 0.011 in corneal nerve fiber length; 15.8 ± 5.2 fibers/mm 2 vs. 14.4 ± 4.3 fibers/mm 2 , P = 0.046 in corneal nerve fiber density), whereas corneal nerve fractal dimension demonstrated a borderline significant decrease ( P = 0.057). Similarly, there was a general declining trend in all epithelial cell parameters with advancing age. Corneal epithelial cell circularity was significantly lower in subjects aged 65 years and older as compared to subjects younger than 65 years (0.722 ± 0.021 μm 2 vs. 0.714 ± 0.021 μm 2 ; P = 0.011). Advancing age results in reduced corneal nerve metrics and alteration of corneal cell morphology. Aging effects should be considered when evaluating patients with corneal neuropathy.

Parental Corneal Tomographic and Biomechanical Characteristics of Patients With Keratoconus

To investigate the hereditability of corneal tomographic and biomechanical parameters in keratoconus (KC). Prospective cohort study. This study was conducted at Qingdao Eye Hospital of Shandong First Medical University in Qingdao, China. Forty-four patients with KC and their biological parents (n=88) were recruited as the study group. The control group consisted of 84 healthy adults with matched age and gender. Both eyes of each participant underwent clinical examinations, and 1 eye was selected for statistical analysis. Exclusion criteria were as follows: individuals with glaucoma, ocular surgery, systemic diseases known to affect the eyes, or poor cooperation during examination. Subjects were asked to discontinue soft contact lens (CL) wear for 2 weeks and rigid gas permeable CL wear for 4 weeks before ocular examination. All participants underwent a comprehensive assessment including Pentacam Scheimpflug tomography, Corvis ST, visual acuity, refraction examination, axial length, and slitlamp examination for both eyes. Individuals presenting with KC manifestations in at least 1 eye were classified as having KC. A total of 9 Pentacam indices including keratometry in the flat/steep meridian (K1/K2), maximal keratometry (Kmax), thinnest point pachymetry (TP), and maximum/average Ambrósio relational thickness (ARTmax/ARTave), anterior and posterior surfaces elevation of the cornea (Ef/Eb) and total deviation value (Final D), and 21 biomechanical indices were collected. Associations of these factors with KC were evaluated using multiple comparison and binary logistics regression analyses. Two parents (2.27%) from 2 different families were diagnosed with KC. Parents of patients with KC had thinner corneas with altered corneal biomechanical parameters compared with healthy controls (P < .05). The combined tomographic and biomechanical index demonstrated the highest discriminatory power (area under the receiver operating characteristic curve 0.785) and strong specificity (84.5%). Parental corneal tomographic and biomechanical index, Corvis biomechanical index, and TP were identified as the major influential factors for KC in their offspring by logistic regression analysis, with a 73.3% accuracy in identifying offspring with KC. Parental corneal tomographic and biomechanical properties of patients with KC suggest a possible predisposition to KC. A combination of tomography and corneal biomechanics can be helpful in predicting the incidence rate of KC in the offspring of patients with subclinical KC.

Experimental glaucoma triggers a pro-oxidative and pro-inflammatory state in the rat cornea

BackgroundIncreasing evidence suggests that glaucoma affects the ocular surface. We aimed to investigate the cellular mechanisms underlying the glaucoma-associated corneal alterations in an animal model. MethodsWistar rats underwent the cauterization of two episcleral veins of the left eye to elevate the intraocular pressure (ipsilateral, G-IL). Control animals received a sham procedure (C-IL). Contralateral eyes did not receive any procedure (G-CL or C-CL). Enzymes related to the redox status, oxidative damage to macromolecules, and inflammatory markers were assessed in corneal lysates. ResultsCompared to C-IL, NOX4, NOX2, and iNOS expression was increased in G-IL (68%, p < 0.01; 247%, p < 0.01; and 200%, p < 0.001, respectively). We found an increase in SOD activity in G-IL (60%, p < 0.05). The GSH/GSSG ratio decreased in G-IL (80%, p < 0.05), with a decrease in GR activity (40%, p < 0.05). G-IL displayed oxidative (90%, p < 0.01) and nitrosative (40%, p < 0.05) protein damage, and enhanced lipid peroxidation (100%, p < 0.01). G-IL group showed an increased in CD45, CD68 and F4/80 expression (50%, p < 0.05; 190%, p < 0.001 and 110%, p < 0.05, respectively). G-CL displayed a higher expression of Nrf2 (60%, p < 0.001) and increased activity of SOD, CAT, and GPx (60%, p < 0.05; 90%, p < 0.01; and 50%, p < 0.05, respectively). ConclusionsGlaucoma induces a redox imbalance in the ipsilateral cornea with an adaptive response of the contralateral one. General significanceOur study provides a possible mechanism involving oxidative stress and inflammation that explains the corneal alterations observed in glaucoma. We demonstrate that these changes extend not only to the ipsilateral but also to the contralateral cornea.

Corneal Endothelial Morphological Alterations in Type 2 Diabetes: Associations with Glycemic Control, Disease Duration, and Diabetic Retinopathy Severity—A Cross-Sectional Study in Benghazi, Libya

Background The corneal endothelium is essential for maintaining corneal transparency and fluid regulation, and its dysfunction can lead to corneal edema and decreased visual acuity. Corneal specular microscopy is used to detect corneal disorders early. Aim This study aimed to evaluate morphological changes in the corneal endothelium of patients with type 2 diabetes mellitus (DM) using specular microscopy. Methods This study enrolled 50 individuals with type 2 diabetes and 50 nondiabetic individuals as control subjects. Patients with certain ocular and systemic conditions were excluded. The collected data included demographic information, medical history, recent hemoglobin A1c (HbA1c) values, visual acuity, ophthalmological examination, and diabetic retinopathy (DR) staging. The corneal endothelial morphology was evaluated using a noncontact specular microscope, which measured corneal endothelial cell density (ECD), central corneal thickness (CCT), coefficient of variation of cell size (CV), and hexagonality. The data were analyzed using SPSS software, and the results were presented as mean ± standard deviation, numbers, and percentages. An unpaired t-test was used to compare different means, and a p-value less than 0.05 was considered statistically significant. Results A majority of diabetic patients (62%) had diabetes for more than 10 years, and 58% of them had higher than 7.5% HbA1c levels. In terms of DR severity, 46% of patients had mild nonproliferative diabetic retinopathy (NPDR), 36% had moderate NPDR, and 10% had severe NPDR. There were significant differences between diabetic and nondiabetic groups in corneal ECD (2480 ± 223 cells/mm2 for DM group vs. 2652 ± 234 cells/mm2 for non-DM), hexagonality (39.6 ± 2.8% for DM group vs. 47 ± 2.1% for non-DM), CV (42 ± 2.9% for DM group vs. 35.5 ± 2.3% for non-DM), and CCT (550 ± 14.8 µm for DM group vs. 530 ± 9.6 µm for non-DM). Patients who had diabetes for more than 10 years had significantly lower ECD (2356 cells/mm2 vs. 2689 cells/mm2), lower hexagonality (39 vs. 41%), and higher CV (43 vs. 41%) and higher CCT (553.9 ± 4.6 vs. 545.5 ± 4.0) than those with less than 10 years of diabetes. As the severity of DR increased, there was a significant decrease in ECD (from 2641 ± 194 cells/mm2 for mild NPDR to 2310 ± 82 cells/mm2 for severe PDR), a decrease in hexagonality (from 40.9 ± 3.2% for mild PDR to 37.4 ± 1.1% for severe PDR), an increase in CV (from 40.1 ± 2.3% for mild PDR to 44 ± 2.9% for severe PDR), and an increase in CCT (from 543.7 ± 13.8 for mild PDR 563.8 ± 2.9 for severe PDR). Conclusion This study revealed that type 2 diabetes is associated with significant reductions in ECD and hexagonality, as well as an increase in CV and CCT. The severity of DR and the duration of diabetes were correlated with changes in these parameters. These findings underscore the need for a comprehensive evaluation of corneal health in diabetic patients.

Prevalence and clinical characteristics of neurotrophic keratopathy in hispanic population in northeastern Mexico

PurposeTo evaluate the prevalence and clinical characteristics of neurotrophic keratopathy (NK) in northeastern Mexico.MethodsRetrospective cross-sectional study in which NK patients admitted to our ophthalmology clinic between 2015 and 2021 were consecutively enrolled. Data regarding demographics, clinical characteristics, and comorbidities were collected at the time diagnosis of NK was made.ResultsIn the period from 2015 to 2021, a total of 74,056 patients were treated and of these 42 had a diagnosis of neurotrophic keratitis. The prevalence found was 5.67 [CI95 3.95–7.38] in 10,000 cases. The mean age observed was 59 ± 17.21 years occurring more frequently in males in 59% and with corneal epithelial defects in 66.7%. The most frequent antecedents were the use of topical medications in 90%, the presence of diabetes mellitus 2 in 40.5% and systemic arterial hypertension in 26.2%. A higher proportion of male patients with corneal alterations and a higher proportion of female patients with corneal ulcerations and/or perforation were observed.ConclusionNeurotrophic keratitis is an underdiagnosed disease with a broad clinical spectrum. The antecedents that were contracted corroborate what was reported in the literature as risk factors. The prevalence of the disease in this geographical area was not reported, so it is expected to increase over time when searching for it intentionally.