Development of graphitic carbon nitride quantum dots-based oxygen self-sufficient platforms for enhanced corneal crosslinking.

Keratoconus, a disorder characterized by corneal thinning and weakening, results in vision loss. Corneal crosslinking (CXL) can halt the progression of keratoconus. The development of accelerated corneal crosslinking (A-CXL) protocols to shorten the treatment time has been hampered by the rapid depletion of stromal oxygen when higher UVA intensities are used, resulting in a reduced cross-linking effect. It is therefore imperative to develop better methods to increase the oxygen concentration within the corneal stroma during the A-CXL process. Photocatalytic oxygen-generating nanomaterials are promising candidates to solve the hypoxia problem during A-CXL. Biocompatible graphitic carbon nitride (g-C3N4) quantum dots (QDs)-based oxygen self-sufficient platforms including g-C3N4 QDs and riboflavin/g-C3N4 QDs composites (RF@g-C3N4 QDs) have been developed in this study. Both display excellent photocatalytic oxygen generation ability, high reactive oxygen species (ROS) yield, and excellent biosafety. More importantly, the A-CXL effect of the g-C3N4 QDs or RF@g-C3N4 QDs composite on male New Zealand white rabbits is better than that of the riboflavin 5'-phosphate sodium (RF) A-CXL protocol under the same conditions, indicating excellent strengthening of the cornea after A-CXL treatments. These lead us to suggest the potential application of g-C3N4 QDs in A-CXL for corneal ectasias and other corneal diseases.

Accuracy of a novel method for IOP measurement without applying pressure on the cornea.

PURPOSE: To assess the accuracy of a prototype novel instrument for intra ocular pressure (IOP) measurements not involving corneal pressure application. DESIGN: Prospective case control study. METHODS: An institutional study including 16 healthy volunteers without ocular pathology. IOP in both eyes of the participants was measured four times in different body positions with the novel prototype and reference instrument (Goldmann applanation tonometer (GAT) or iCare (iCare Finland OY, Vantaa, Finland)). IOP results were compared between the prototype and the reference instruments in 116 pairs of measurement. RESULTS: Overall no statistically significant difference was found between the presented prototype and the reference instrument. Stratifying measurements by instrument used revealed no significant difference for GAT and statistical significant (yet clinically insignificant) difference for iCare. CONCLUSIONS: The presented prototype demonstrates good clinical agreement of IOP measuring results with reference instruments Further large-scale studies assessing this instrument in glaucoma patients are warranted.

[Study of the growth temperature of ocular surface microorganisms in norm and in infectious keratitis]. / Izuchenie temperaturnykh uslovii rosta mikroorganizmov glaznoi poverkhnosti v norme i pri infektsionnykh keratitakh.

Standard bacteriological examinations, which involve culturing microorganisms at 37 °C, are commonly used in clinical practice for diagnosing infectious diseases. However, the growth temperature of microorganisms on the ocular surface (OS) during infectious keratitis (IK) may not coincide with the laboratory standard, which is due to the characteristic features of heat exchange in the eye. PURPOSE: This exploratory study examines the distribution and properties of OS microorganisms isolated under different temperature cultivation conditions in patients with IK and healthy volunteers without ophthalmic pathology. MATERIAL AND METHODS: Fifteen participants were divided into two groups. Group 1 (n=10) consisted of patients with signs of unilateral infectious keratitis, while group 2 (n=5) served as the control group. A novel microbiological method was employed to isolate pure cultures of microorganisms. This method involved cultivating microorganisms at two temperature regimes (37 °C and 24 °C) and subsequently identifying them using biochemical, immunological, and physicochemical techniques, including mass spectrometry. Scanning electron microscopy (SEM) with lanthanide staining used as the reference method. The temperature status of the ocular surface was assessed using non-contact infrared thermography. RESULTS: The study demonstrated the presence of psychrotolerant microorganisms on the ocular surface, which exhibited growth at a relatively low temperature of 24 °C. These psychrotolerant microorganisms were found to be isolated from the ocular surface displaying signs of temperature dysregulation. Among such microorganisms are Acinetobacter lwoffii, Achromobacter xylosoxidans, Bacillus licheniformis, Enterococcus faecalis, Klebsiella oxytoca, Klebsiella pneumoniae, Micrococcus luteus, Pseudomonas luteola, Streptococcus spp. CONCLUSION: When identifying the causative agent of infectious keratitis, it is crucial to consider the divergence of growth temperature of ocular surface microorganisms. The presence of psychrotolerant microorganisms on the ocular surface, which can effectively grow at room temperature, should be taken into account, especially in cases of temperature dysregulation.

[Changes in the precorneal tear film at various stages of keratoconus]. / Izmenenie prekorneal'noi sleznoi plenki pri razlichnykh stadiyakh keratokonusa.

The combination of keratoconus (KC) with signs of dry eye disease (DES) has been described in numerous scientific publications. At the same time, there is a relationship between KC stage and an increase in the severity of DES symptoms, however, there is still no common understanding of the severity of xerotic process depending on the clinical course of keratectasia. PURPOSE: This study assesses the changes in the state of the precorneal tear film in KC relative to the stages of the disease. MATERIAL AND METHODS: The study included 50 patients (100 eyes) with bilateral non-operated KC from subclinical to stage IV. The following methods were used for a comprehensive assessment of the condition of the tear film: biomicroscopy of the anterior segment of the eye using vital dyes, functional tests (Norn, Schirmer, Jones tests), tearscopy of the lipid layer of the tear film with software processing of the results, OCT-meniscometry, as well as filling out the OSDI questionnaire by patients. RESULTS: The following significant changes were revealed as the KC stage progressed: an increase in the area of staining of the ocular surface with vital dyes, a decrease in the results of the Norn functional test and OCT-meniscometry, an increase in the areas of smaller thickness of lipids and areas of their complete absence according to tearscopy, as well as an increase in scores of the OSDI questionnaire. CONCLUSION: A comprehensive assessment of the condition of the tear film in KC indicates the relationship and the strengthening of the signs of DES as keratectasia progresses, and can be considered as justification for the need to prescribe tear replacement and reparative therapy that improves the condition of the ocular surface and stabilizes the precorneal tear film.

Visual restoration with KPro after face allotransplantation with a grade III phthisical eye.

The Boston Keratoprosthesis type I (KPro-I) has been shown to be successful in restoring vision after severe ocular burns; however, its long-term outcomes in phthisical eyes have rarely been reported. A monocular woman with a history of severe alkali chemical injury necessitating facial transplantation presented with a light perception left eye after a complicated course, including failed KPro-I, therapeutic penetrating keratoplasty, endophthalmitis, hypotony, total retinal detachment, and structural changes, including a shrunken 18 mm axial length and eye wall thickening. The patient underwent a combined vitrectomy with silicone oil and KPro-I implantation, resulting in her regaining ambulatory visual acuity (20/250) at 3 years' follow-up.

Drug-eluting contact lenses: Progress, challenges, and prospects.

Topical ophthalmic solutions (eye drops) are becoming increasingly popular in treating and preventing ocular diseases for their safety, noninvasiveness, and ease of handling. However, the static and dynamic barriers of eyes cause the extremely low bioavailability (<5%) of eye drops, making ocular therapy challenging. Thus, drug-eluting corneal contact lenses (DECLs) have been intensively investigated as a drug delivery device for their attractive properties, such as sustained drug release and improved bioavailability. In order to promote the clinical application of DECLs, multiple aspects, i.e., drug release and penetration, safety, and biocompatibility, of these drug delivery systems were thoroughly examined. In this review, we systematically discussed advances in DECLs, including types of preparation materials, drug-loading strategies, drug release mechanisms, strategies for penetrating ocular barriers, in vitro and in vivo drug delivery and penetration detection, safety, and biocompatibility validation methods, as well as challenges and future perspectives.

Case report: Nerve fiber regeneration in children with melanocortin 4 receptor gene mutation related obesity treated with semaglutide.

Melanocortin 4 receptor (MC4R) mutations are the commonest cause of monogenic obesity through dysregulation of neuronal pathways in the hypothalamus and prefrontal cortex that regulate hunger and satiety. MC4R also regulates neuropathic pain pathways via JNK signaling after nerve injury. We show evidence of corneal small fiber degeneration in 2 siblings carrying a heterozygous missense variant c.508A>G, p.Ille170Val in the MC4R gene. Both children were treated with once weekly semaglutide for 6 months with no change in weight, and only a minor improvement in HbA1c and lipid profile. However, there was evidence of nerve regeneration with an increase in corneal nerve fiber density (CNFD) [child A (13.9%), child B (14.7%)], corneal nerve branch density (CNBD) [child A (110.2%), child B (58.7%)] and corneal nerve fiber length (CNFL) [child A (21.5%), child B (44.0%)].

The role of graft cross-linking during keratoplasty in patients with corneal melting.

The purpose of this study was to investigate the role of corneal crosslinking (CXL) of grafts during keratoplasty (KP) in patients with refractory corneal melting (CM). This is a retrospective case series reporting the clinical outcomes of patients who received a crosslinked corneal graft during penetrating or deep anterior lamellar KP for refractory infectious or sterile CMs. Outcome measures were the recurrence of CM, the time required for epithelial healing following KP, incidence of complications, and necessity for re-transplantation. Twenty eyes of 18 patients with a follow-up of 29.2 ± 15.8 months were included in this study. All but two eyes had undergone previous KPs during the course of their disease (mean 1.9 ± 1.6). After CXL-enhanced KP, three eyes (15%) experienced recurrence of CM, three eyes developed an infectious keratitis and six eyes (30%) required a re-transplantation (three of them within 12 months). The mean time to epithelium closure after CXL-enhanced KP was 63 ± 90 days. The number of postoperative re-transplantations was significantly lower than the number of KPs performed before the CXL-enhanced transplantation (before CXL 1.9 ± 1.6 vs after CXL: 0.3 ± 0.57, p = 0.002). To conclude, CXL of the graft at the time of keratoplasty decreased the need for re-transplantations. However, further studies are needed in order to establish its role in the management of severe CM necessitating therapeutic corneal transplantation.

Potential therapeutic effects of peroxisome proliferator-activated receptors on corneal diseases.

The cornea is an avascular tissue in the eye that has multiple functions in the eye to maintain clear vision which can significantly impair one's vision when subjected to damage. Peroxisome proliferator-activated receptors (PPARs), a family of nuclear receptor proteins comprising three different peroxisome proliferator-activated receptor (PPAR) isoforms, namely, PPAR alpha (α), PPAR gamma (γ), and PPAR delta (δ), have emerged as potential therapeutic targets for treating corneal diseases. In this review, we summarised the current literature on the therapeutic effects of PPAR agents on corneal diseases. We discussed the role of PPARs in the modulation of corneal wound healing, suppression of corneal inflammation, neovascularisation, fibrosis, stimulation of corneal nerve regeneration, and amelioration of dry eye by inhibiting oxidative stress within the cornea. We also discussed the underlying mechanisms of these therapeutic effects. Future clinical trials are warranted to further attest to the clinical therapeutic efficacy.

The Role of Vimentin in Human Corneal Fibroblast Spreading and Myofibroblast Transformation.

Vimentin has been reported to play diverse roles in cell processes such as spreading, migration, cell-matrix adhesion, and fibrotic transformation. Here, we assess how vimentin impacts cell spreading, morphology, and myofibroblast transformation of human corneal fibroblasts. Overall, although knockout (KO) of vimentin did not dramatically impact corneal fibroblast spreading and mechanical activity (traction force), cell elongation in response to PDGF was reduced in vimentin KO cells as compared to controls. Blocking vimentin polymerization using Withaferin had even more pronounced effects on cell spreading and also inhibited cell-induced matrix contraction. Furthermore, although absence of vimentin did not completely block TGFß-induced myofibroblast transformation, the degree of transformation and amount of αSMA protein expression was reduced. Proteomics showed that vimentin KO cells cultured in TGFß had a similar pattern of protein expression as controls. One exception included periostin, an ECM protein associated with wound healing and fibrosis in other cell types, which was highly expressed only in Vim KO cells. We also demonstrate for the first time that LRRC15, a protein previously associated with myofibroblast transformation of cancer-associated fibroblasts, is also expressed by corneal myofibroblasts. Interestingly, proteins associated with LRRC15 in other cell types, such as collagen, fibronectin, ß1 integrin and α11 integrin, were also upregulated. Overall, our data show that vimentin impacts both corneal fibroblast spreading and myofibroblast transformation. We also identified novel proteins that may regulate corneal myofibroblast transformation in the presence and/or absence of vimentin.

TGF-ß-Based Therapies for Treating Ocular Surface Disorders.

The cornea is continuously exposed to injuries, ranging from minor scratches to deep traumas. An effective healing mechanism is crucial for the cornea to restore its structure and function following major and minor insults. Transforming Growth Factor-Beta (TGF-ß), a versatile signaling molecule that coordinates various cell responses, has a central role in corneal wound healing. Upon corneal injury, TGF-ß is rapidly released into the extracellular environment, triggering cell migration and proliferation, the differentiation of keratocytes into myofibroblasts, and the initiation of the repair process. TGF-ß-mediated processes are essential for wound closure; however, excessive levels of TGF-ß can lead to fibrosis and scarring, causing impaired vision. Three primary isoforms of TGF-ß exist-TGF-ß1, TGF-ß2, and TGF-ß3. Although TGF-ß isoforms share many structural and functional similarities, they present distinct roles in corneal regeneration, which adds an additional layer of complexity to understand the role of TGF-ß in corneal wound healing. Further, aberrant TGF-ß activity has been linked to various corneal pathologies, such as scarring and Peter's Anomaly. Thus, understanding the molecular and cellular mechanisms by which TGF-ß1-3 regulate corneal wound healing will enable the development of potential therapeutic interventions targeting the key molecule in this process. Herein, we summarize the multifaceted roles of TGF-ß in corneal wound healing, dissecting its mechanisms of action and interactions with other molecules, and outline its role in corneal pathogenesis.

Modified femtosecond laser-assisted arcuate keratotomy for managing low corneal astigmatism using trifocal intraocular lens implantation in Chinese cataract patients.

To evaluate the visual outcome and astigmatic correction following trifocal intraocular lens (IOL) implantation using the modified femtosecond laser-assisted arcuate keratotomy (FSAK) in Chinese cataract patients with low astigmatism. This retrospective study included consecutive cataract patients with regular corneal astigmatism ranging from 0.75 to 1.5 D who underwent FSAK combined with the trifocal IOL implantation between November 2020 and September 2022. Monocular uncorrected distance visual acuity, uncorrected intermediate visual acuity, uncorrected near visual acuity, and refractive data were collected at the 3-month follow-up. The pre- and post-operative high-order aberrations (HOAs) were recorded. The variation in astigmatism was analyzed using Alpins vector analysis. A total of 27 eyes from 23 patients were analyzed. The monocular uncorrected distance visual acuity (UDVA) (5 m) at the 3-month follow-up was 0.04 ± 0.09 logarithm of the minimum angle of resolution (logMAR), which was significantly improved compared with the preoperative value of 0.95 ± 0.51 logMAR (P <.001). The corneal astigmatism was significantly reduced from 1.24 ± 0.42 D to 0.49 ± 0.34 D (P <.001). The target-induced astigmatism (TIA) was 1.25 ± 0.43 D, the surgically induced astigmatism (SIA) was 1.16 ± 0.52 D, and the difference vector (DV) was 0.5 ± 0.34 D. The magnitude of error (ME) (difference between SIA and TIA) was -0.1 ± 0.41 D, and the correction index (CI) (ratio of SIA to TIA) was 0.93 ± 0.36. The angle of error was 3.92° ± 16.90°. Total HOA was reduced from 0.89 ± 1.11 to 0.41 ± 0.55 (P = 0.184), and the corneal HOA was lowered from 0.17 ± 0.18 to 0.10 ± 0.10 (P = 0.129). Implantation of trifocal IOL following the modified FSAK in Chinese cataract patients exhibited excellent visual efficacy and effectively reduced corneal astigmatism.

A case of prolonged corneal sulfur foreign bodies and review of literature.

BACKGROUND: This case mainly describes a relatively rare case of an old mineral-like corneal foreign body that existed for up to 20 years, and did not significantly affect the visual quality of the patient. CASE PRESENTATION: A 56-year-old male miner complained of right eye vision loss for 3 years, swollen and painful for 4 months. Admission examination: Best corrected visual acuity was no light perception in the right eye and 20/20 in the left eye. Anterior segment examination: A large number of spot-like grayish-brown mineral foreign bodies in the conjunctiva of the nasal conjunctiva, emulsified silicone oil floating in the anterior chamber, Corneal foreign bodies in the right eye were widely distributed in the upper cortex and the proelastic layer. There were fewer foreign bodies in the left cornea. Previous medical history, 20 years ago due to forging and burning sulphur mine explosion, resulting in a large number of ore foreign bodies in the conjunctiva of both eyes. As these corneal foreign bodies did not affect the visual quality of the patient, we adopted a conservative treatment plan, did not remove these foreign bodies, and only carried out symptomatic treatment for the patient's secondary ocular hypertension. The patient was followed up normally in the outpatient department, and no cornea-related complications occurred up to now. CONCLUSIONS: First of all, it is necessary to understand the source and nature of the foreign body in patients with corneal and conjunctival foreign body injuries. In the second, for the old corneal metal foreign body, when the patient's visual acuity is stable and there are no symptoms of corneal irritation and inflammatory reaction, it can be Conservative treatment or outpatient follow-up observation. In the end, corneal Optical coherence tomography imaging should not be ignored, which is very important for determining the depth of embedding and the location of the corneal foreign body.

Biomechanical changes of the cornea after orbital decompression in thyroid-associated orbitopathy measured by corvis ST.

This study aims to investigate the changes in ocular biomechanical factors in patients with inactive thyroid eye disease (TED) who undergo orbital decompression surgery. This observational prospective study include 46 eyes of 31 patients with inactive TED undergoing orbital decompression at a tertiary university hospital from October 2021 to September 2023. All participants underwent a full ophthalmic examination, and a biomechanical examination was performed using corvis ST at baseline, 1 month, and 3 months postoperatively. The study participants had a mean age of 45 ± 11.6 years, and 58.1% of them were female. The second applanation time (A2T) increased from baseline to postoperative month 1 and continued to increase to postoperative month 3 (P < 0.001). The first applanation velocity (A1V), highest concavity (HC) peak distance, and pachymetry parameters also increased from postoperative month 1 to postoperative month 3 (P = 0.035, P = 0.005, and P = 0.031, respectively). The HC time increased from baseline to postoperative month 3 (P = 0.027). Other changes were statistically insignificant. The P-values were adjusted according to biomechanically corrected intraocular pressure (bIOP). Baseline Hertel significantly influenced A2 time (P < 0.001). Our findings suggest that ocular biomechanical parameters may change following decompression surgery in patients with inactive TED. Specifically, an increase in A2T, A1V, and HC peak distance suggests a decrease in corneal stiffness, although the increased HC time contradicts this. It is recommended to postpone keratorefractive or intraocular lens implantation surgeries until corneal biomechanics stabilize after decompression surgery for optimal results.

Corneal nerve fiber morphology following COVID-19 infection in vaccinated and non-vaccinated population.

To examine corneal subbasal nerve changes in patients who received vaccination against SARS-CoV-2 virus and underwent COVID-19 infection compared to infected non-vaccinated patients and healthy controls. Twenty-nine eyes of 29 vaccinated patients (mean age: 36.66 ± 12.25 years) within six months after PCR or Ag test proven COVID-19 infection and twenty-eight eyes of 28 age-matched infected, non-vaccinated patients (mean age: 42.14 ± 14.17 years) were enrolled. Twenty-five age-matched healthy individuals (mean age: 47.52 ± 18.45 years) served as controls. In vivo confocal microscopy (Heidelberg Retina Tomograph II Rostock Cornea Module, Germany) was performed in each group. Corneal subbasal nerve plexus morphology and corneal dendritic cells (DC) were evaluated. Significantly higher corneal nerve fiber density (P < 0.001), nerve branch density (P < 0.001), nerve fiber length (P < 0.001), total branch density (P = 0.007), nerve fiber area (P = 0.001) and fractal dimension (P < 0.001) values were observed in vaccinated patients after COVID-19 infection compared to the non-vaccinated group. Significantly higher DC density was observed in the non-vaccinated group compared to the control group (P = 0.05). There was a statistically significant difference in the size of mature DCs (P < 0.0001) but the size of immature DCs did not differ significantly among the 3 groups (P = 0.132). Our results suggest that SARS-CoV-2 vaccination may have a protective effect against the complications of COVID-19 disease on the corneal subbasal nerve fibers.

Pseudonectria keratitis-emerging pathogenic fungi in the eye.

BACKGROUND: Infectious keratitis, a significant contributor to blindness, with fungal keratitis accounting for nearly half of cases, poses a formidable diagnostic and therapeutic challenge due to its delayed clinical presentation, prolonged culture times, and the limited availability of effective antifungal medications. Furthermore, infections caused by rare fungal strains warrant equal attention in the management of this condition. CASE PRESENTATION: A case of fungal keratitis was presented, where corneal scraping material culture yielded pink colonies. Lactophenol cotton blue staining revealed distinctive spore formation consistent with the Fusarium species. Further analysis using Matrix-Assisted Laser Desorption/Ionization Time-of-Flight Mass Spectrometry (MALDI-TOF MS) identified the causative agent as Fusarium proliferatum. However, definitive diagnosis of Pseudonectria foliicola infection was confirmed through ITS sequencing. The patient's recovery was achieved with a combination therapy of voriconazole eye drops and itraconazole systemic treatment. CONCLUSION: Pseudonectria foliicola is a plant pathogenic bacterium that has never been reported in human infections before. Therefore, ophthalmologists should consider Pseudonectria foliicola as a possible cause of fungal keratitis, as early identification and timely treatment can help improve vision in most eyes.

The Role of LC3-Associated Phagocytosis Inhibits the Inflammatory Response in Aspergillus fumigatus Keratitis.

Purpose: The purpose of this study was to investigate the role and mechanism of microtubule-associated protein light chain-3 (LC3)-associated phagocytosis (LAP) in the immune response to Aspergillus fumigatus (A. fumigatus) keratitis. Methods: The formation of single-membrane phagosomes was visualized in the corneas of healthy or A. fumigatus-infected humans and C57BL/6 mice using transmission electron microscopy (TEM). Rubicon siRNA (si-Rubicon) was used to block Rubicon expression. RAW 264.7 cells or mice corneas were infected with A. fumigatus with or without pretreatment of si-Rubicon and scrambled siRNA. RAW 264.7 cells were pretreated with Dectin-1 antibody or Dectin-1 overexpressed plasmid and then stimulated with A. fumigatus. Flow cytometry was used to label macrophages in normal and infected corneas of mice. In mice with A. fumigatus keratitis, the severity of the disease was assessed using clinical scores. We used lentiviral technology to transfer GV348-Ubi-GFP-LC3-II-SV40-Puro Lentivirus into the mouse cornea. The GFP-LC3 fusion protein was visualized in corneal slices using a fluorescence microscope. We detected the mRNA and protein expressions of the inflammatory factors IL-6, IL-1ß, and IL-10 using real-time PCR (RT-PCR) and ELISA. We detected the expression of LAP-related proteins Rubicon, ATG-7, Beclin-1, and LC3-II using Western blot or immunofluorescence. Results: Accumulation of single-membrane phagosomes within macrophages was observed in the corneas of patients and mice with A. fumigatus keratitis using TEM. Flow cytometry (FCM) analysis results show that the number of macrophages in the cornea of mice significantly increases after infection with A. fumigatus. LAP-related proteins were significantly elevated in the corneas of mice and RAW 264.7 cells after infection with A. fumigatus. The si-Rubicon treatment elevated the clinical score of mice. In A. fumigatus keratitis mice, the si-Rubicon treated group showed significantly higher expression of IL-6 and IL-1ß and lower expression of IL-10 and LC3-II compared to the control group. In RAW 264.7 cells, treatment with the Dectin-1 overexpressed plasmid upregulated the expression of LAP-related proteins, a process that was significantly inhibited by the Dectin-1 antibody. Conclusions: LAP participates in the anti-inflammatory immune process of fungal keratitis (FK) and exerts an anti-inflammatory effect. LAP is regulated through the Dectin-1 signaling pathway in A. fumigatus keratitis.

Physiological Effects of Soat1 Inactivation on Homeostasis of the Mouse Ocular Surface.

Purpose: Soat1/SOAT1 have been previously reported to be critical for the biosynthesis of cholesteryl esters (CEs) in the mouse Meibomian glands (MGs) as the loss of function led to an arrest of CE production and a substantial accumulation of nonesterified cholesterol in the meibum, causing an increase in its melting temperature. The purpose of this study was to further investigate the role of Soat1 in meibogenesis and ocular surface physiology. Methods: The mouse ocular features of knockout Soat1-/- and wild type (WT) mice were studied using various ophthalmic and histological techniques, mouse lipidomes were monitored using liquid chromatography/mass spectrometry, whereas their transcriptomes were compared to characterize the effects of the mutation on the gene expression profiles in the MG and cornea. Results: Soat1-/- mice displayed increased tear production and severe corneal abnormalities, such as corneal thinning, (neo)vascularization, ulceration, and opacification that progressed with aging. Transcriptomic analyses led to identification of a range of significantly disrupted pathways, which included general and specific lipid metabolism-related pathways, keratinization, angiogenesis/(neo)vascularization, muscle contraction, and several other pathways. In addition, histological and histochemical experiments revealed morphological changes in the MG, cornea, and conjunctiva in Soat1-/- mice. Notably, the mRNA microarray expression level of Soat1 in WT MGs (log2 17.5) was 1000 × of that in the mouse cornea (log2 7.5). Conclusions: These findings suggest a direct involvement of Soat1/SOAT1 in MGs in maintaining ocular surface homeostasis, in general, and corneal health, specifically.

Tear Fluid Progranulin as a Noninvasive Biomarker for the Monitoring of Corneal Innervation Changes in Patients With Type 2 Diabetes Mellitus.

Purpose: This study aimed to investigate the expression levels of progranulin (PGRN) in the tears of patients with diabetic retinopathy (DR) versus healthy controls. Additionally, we sought to explore the correlation between PGRN levels and the severity of ocular surface complications in patients with diabetes. Methods: In this prospective, single-visit, cross-sectional study, patients with DR (n = 48) and age-matched healthy controls (n = 22) were included and underwent dry eye examinations. Tear fluid was collected, and its components were analyzed using the Luminex assay. The subbasal nerve plexus of all participants was evaluated by in vivo confocal microscopy. Results: Patients with DR exhibited more severe dry eye symptoms, along with a reduction in nerve fiber density, length, and branch density within the subbasal nerve plexus, accompanied by an increase in the number of dendritic cells. Tear PGRN levels were also significantly lower in patients with diabetes than in normal controls, and the levels of some inflammatory factors (TNF-α, IL-6, and MMP-9) were higher in patients with DR. Remarkably, the PGRN level significantly correlated with nerve fiber density (R = 0.48, P < 0.001), nerve fiber length (R = 0.65, P < 0.001), and nerve branch density (R = 0.69, P < 0.001). Conclusions: Tear PGRN levels might reflect morphological changes in the corneal nerve plexus under diabetic conditions, suggesting that PGRN itself is a reliable indicator for predicting the advancement of neurotrophic keratopathy in patients with diabetes. Translational Relevance: PGRN insufficiency on the ocular surface under diabetic conditions was found to be closely associated with nerve impairment, providing a novel perspective to discover the pathogenesis of diabetic complications, which could help in developing innovative therapeutic strategies.

Analysis of the performance of the CorneAI for iOS in the classification of corneal diseases and cataracts based on journal photographs.

CorneAI for iOS is an artificial intelligence (AI) application to classify the condition of the cornea and cataract into nine categories: normal, infectious keratitis, non-infection keratitis, scar, tumor, deposit, acute primary angle closure, lens opacity, and bullous keratopathy. We evaluated its performance to classify multiple conditions of the cornea and cataract of various races in images published in the Cornea journal. The positive predictive value (PPV) of the top classification with the highest predictive score was 0.75, and the PPV for the top three classifications exceeded 0.80. For individual diseases, the highest PPVs were 0.91, 0.73, 0.42, 0.72, 0.77, and 0.55 for infectious keratitis, normal, non-infection keratitis, scar, tumor, and deposit, respectively. CorneAI for iOS achieved an area under the receiver operating characteristic curve of 0.78 (95% confidence interval [CI] 0.5-1.0) for normal, 0.76 (95% CI 0.67-0.85) for infectious keratitis, 0.81 (95% CI 0.64-0.97) for non-infection keratitis, 0.55 (95% CI 0.41-0.69) for scar, 0.62 (95% CI 0.27-0.97) for tumor, and 0.71 (95% CI 0.53-0.89) for deposit. CorneAI performed well in classifying various conditions of the cornea and cataract when used to diagnose journal images, including those with variable imaging conditions, ethnicities, and rare cases.