Longitudinal analysis of wound healing response post SMILE and LASIK surgery using proteomic profiling of tears.

Different types of refractive surgeries often exhibit differences in wound healing responses. The current study investigated post-operative tear protein profiles in subjects who underwent LASIK and SMILE to elucidate global changes to the proteomic profile during the period the patient cornea undergoes healing. In this study, 10 patients underwent LASIK and SMILE surgery with a contralateral paired eye design. Tear samples were collected using Schirmer's strips preoperatively, at 1 month, 3 months and 6 months postoperatively. Quantitative ITRAQ labeled proteomics was performed and the tear protein ratios were normalized to pre-operative protein levels for each subject. Whole proteomics identified 1345 proteins in tears from LASIK and 1584 proteins in SMILE across time points. About 67 proteins were common in LASIK and SMILE tears across all the time points. Wound healing responses were differentially regulated between two refractive surgeries (SMILE and LASIK). The proteins Ceruloplasmin, Clusterin, Serotransferrin were upregulated at 1 month and 3 months and downregulated at 6 months post operatively in LASIK surgery where as in SMILE these were downregulated. Galectin 3 binding protein showed upregulation at 1 month and the levels decreased at 3 months and 6 months postop in LASIK tears whereas the levels increased at 3 months and 6 months post-op in SMILE tears. The levels of proteins that protect from oxidative stress were higher in SMILE as compared to LASIK postoperatively. The extracellular matrix proteins showed an increase in expression at 6 months in SMILE tears and was stabilized at 6 months in LASIK tears post operatively. Different refractive surgeries induce distinct wound healing responses as identified in tears. This study has implications in targeting key proteins for improving the clinical outcome postrefractive surgery.

Corneal Biomechanics and Intraocular Pressure Following Scleral Lens Wear in Penetrating Keratoplasty and Keratoconus.

OBJECTIVE: To compare corneal biomechanics and intraocular pressure (IOP) in keratoconus and penetrating keratoplasty eyes before and after nonfenestrated scleral lens wear. METHODS: Twenty-three participants were enrolled, and 37 eyes were included in the analysis (11 penetrating keratoplasty and 26 keratoconus). A range of corneal biomechanical parameters and IOP were measured using the CORVIS ST before and after 8 hr of nonfenestrated scleral lens wear (Keracare, Acculens, Denver, CO). RESULTS: Before lens wear, penetrating keratoplasty eyes displayed significantly greater median values for central corneal thickness (97 µm thicker, P=0.02), IOP (3.89 mm Hg higher, P=0.01), and biomechanical parameter A2 length (0.48 mm longer, P=0.003) compared with keratoconic eyes. No significant changes in corneal biomechanical parameters or IOP were observed after scleral lens wear in either group (all P>0.05). CONCLUSION: Although nonfenestrated scleral contact lenses can induce a subatmospheric pressure after lens settling and compress tissue surrounding the limbus, no significant changes were detected in the corneal biomechanical parameters studied using CORVIS ST after scleral lens wear in eyes with penetrating keratoplasty and keratoconus.

Quantitative Proteomics Reveals Molecular Network Driving Stromal Cell Differentiation: Implications for Corneal Wound Healing.

The differentiation of keratocytes to fibroblasts and myofibroblasts is an essential requisite during corneal wound closure. The aim of this study is to uncover factors involved in differentiation-dependent alteration in the protein profile of human corneal stromal cells using quantitative proteomics. Human corneal fibroblasts were cultured and differentiated into keratocytes in serum-free media and myofibroblasts through treatment with TGF-ß. The protein cell lysates from the donors were tryptic and were digested and labeled using a 3-plex iTRAQ kit. The labeled peptides were subjected to LCMS analysis. Biological functional analysis revealed a set of crucial proteins involved in the differentiation of human corneal stromal cells which were found to be significantly enriched. The selected proteins were further validated by immunohistochemistry. Quantitative proteomics identified key differentially expressed proteins which are involved in cellular signaling pathways. Proteins involved in integrin signaling (Ras-RAP1b, TLN and FN) and SLIT-ROBO pathways (PFN1, CAPR1, PSMA5) as well as extracellular matrix proteins (SERPINH1, SPARC, ITGß1, CRTAP) showed enhanced expression in corneal fibroblasts and myofibroblasts compared to keratocytes, indicating their possible role in wound healing. Corneal stromal cell differentiation is associated with the activation of diverse molecular pathways critical for the repair of fibroblasts and myofibroblasts. Identified proteins such as profilin 1 and talin could play a tentative role in corneal healing and serve as a potential target to treat corneal fibrosis.

The effect of scleral lenses on vision, refraction and aberrations in post-LASIK ectasia, keratoconus and pellucid marginal degeneration.

PURPOSE: To quantify the effect of a single scleral lens design on visual acuity and ocular higher-order aberrations in eyes with post-LASIK ectasia, keratoconus and pellucid marginal degeneration (PMD) that could not achieve satisfactory vision with spectacles or soft contact lenses. METHODS: Forty-six eyes of 28 participants fitted with diagnostic scleral lenses (KeraCare) were analysed, including 19, 15 and 12 eyes with post-LASIK ectasia, keratoconus and PMD, respectively. Corrected distance visual acuity (CDVA) and ocular aberrations were measured prior to lens wear and during lens wear after 60 min of settling. An i-Trace aberrometer was used to determine aberrations over a 4.5 mm diameter pupil. RESULTS: Before lens wear, the median (95% confidence interval) values across all groups were: CDVA 0.30 (0.30, 0.40) logMAR, spherical equivalent refraction -2.75 (-5.25, -2.12) D, cylindrical refraction 3.75 (2.50, 5.00) D, higher-order-root-mean-square error (HO-RMS) 0.90 (0.64, 1.03) µm and vertical coma co-efficient C(3,-1) -0.32 (-0.42, -0.12) µm. RMS coma of 0.52 (0.40, 0.74) µm was higher for the keratoconus group than for the other groups (p < 0.05). During lens wear, values improved considerably across all groups: CDVA 0.0 (0.0, 0.00) logMAR, spherical equivalent refraction -0.50 (-0.75, +0.50) D, cylindrical refraction 0.50 (0.00, 0.50) D, HO-RMS 0.32 (0.26, 0.42) µm and C(3,-1) +0.12 (+0.02, +0.19) µm (all p < 0.001 compared to pre-lens wear). While reduced significantly, RMS coma remained higher in the keratoconus group at 0.35 (0.31, 0.52) µm than in the post-LASIK ectasia and PMD groups at 0.17 (0.12, 0.21) µm and 0.07 (0.02, 0.46) µm, respectively (p < 0.05). CONCLUSIONS: The KeraCare scleral contact lens reduced ocular aberrations and improved visual acuity in patients with post-LASIK ectasia, keratoconus and PMD. The sign of vertical coma changed in keratoconus and PMD.

Scleral Lens Visual Rehabilitation of Sequential Bilateral Corneal Hydrops With Post-LASIK Ectasia.

ABSTRACT: This case report describes a unique presentation of bilateral sequential acute corneal hydrops that manifested several years after laser in situ keratomileusis. Initial management included anterior chamber perfluoropropane gas injection and corneal suturing. Longer-term visual rehabilitation involved the use of scleral lenses which significantly reduced lower- and higher-order ocular aberrations.

Early biological responses in ocular tissue after SMILE and LASIK surgery.

We studied the early protein profile in the ocular tissue extracted after LASIK and SMILE surgery. SMILE and LASIK was performed in contralateral eyes and stromal tissue samples were collected from 10 eyes of 5 donors. The stromal tissue samples were analyzed using label free quantification approach and ITRAQ labelling approach in LC-MS/MS. Combined functional analysis revealed many differentially expressed proteins which were involved in important biological processes. About 117 unique differentially expressed proteins were identified using two different proteomic approaches. Collagens, proteoglycans, corneal crystallins were enriched and showed differential expression in SMILE and LASIK as compared to the non-surgical control. Apart from these, 14-3-3 class of proteins, Lysozyme (LYZ), Macrophage Migratory Inhibitory Factor protein (MIF), Pigment Epithelial Derived Factor (PEDF) were differentially expressed when compared between LASIK and SMILE. Peroxiredoxin 1 (PRDX1) expression was found to be reduced in LASIK as compared to SMILE. The expression of Lysozyme C and Macrophage Migratory Inhibitory Factor inflammatory response was found to be less in SMILE as compared to LASIK. Western blot validation of specific markers such as Collagen IV (COL4), Keratocan (KERA), Lumican (LUM), Aldehyde dehydrogenase 3 A1 (ALDH3A1), Lysozyme C (LYZC) confirmed the differences in the protein levels observed in SMILE and LASIK operated tissues as compared to non-surgical controls. In conclusion, this study revealed the early molecular changes occurring in the cornea resulting from these two surgical procedures which may have implications on managing post-operative complications.

Scleral Lens-Induced Corneal Edema after Penetrating Keratoplasty.

SIGNIFICANCE: Modern highly oxygen-permeable nonfenestrated scleral lenses induce approximately 1 to 2% corneal edema after short periods of lens wear in healthy individuals. This study investigated the magnitude and regional variation in scleral lens-induced central corneal edema after penetrating keratoplasty. PURPOSE: The purpose of this study was to examine the magnitude and regional variation in corneal edema after a short period of scleral lens wear in post-penetrating keratoplasty eyes and a control group of eyes with healthy corneas. METHODS: Nine post-penetrating keratoplasty eyes (nine participants; mean age, 32 years) were fitted with highly oxygen-permeable nonfenestrated scleral lenses (Dk 100 × 10 cm O2 (cm)/[(s) (cm) (mmHg)]). Central corneal thickness was measured using Scheimpflug imaging before lens insertion and immediately after lens removal (mean wearing time, 6.2 hours). Corneal edema was quantified across the central 6 mm and compared with data obtained from a historical control group of healthy eyes using a similar experimental paradigm. RESULTS: Post-penetrating keratoplasty eyes exhibited significant corneal edema after lens wear (2.99% [95% confidence interval, 1.13 to 4.85%]) averaged across the central 6 mm (P = .006) and regional variations in edema (P < .001) (greater swelling toward the graft-host junction inferiorly). Compared with healthy eyes, post-penetrating keratoplasty eyes displayed a greater magnitude of corneal edema (by ~3×) and greater variability in the corneal response (by ~2.5×). CONCLUSIONS: Scleral lens-induced central corneal edema is greater in post-penetrating keratoplasty eyes and varies regionally compared with healthy corneas after short-term wear. Lens design and fitting factors contributing to hypoxic and mechanical corneal stress should be carefully considered for all post-penetrating keratoplasty scleral lens fits to minimize potential graft rejection or failure in the longer-term.

Insights into atypical segmental layer thicknesses and phase retardation in thick corneas using ultrahigh-resolution polarization-sensitive optical coherence tomography.

BACKGROUND: Accurately assessing corneal structural status is challenging when thickness deviates from the average. Polarization-sensitive optical coherence tomography (PS-OCT) measures tissue-specific polarization changes, providing additional contrast for accurate segmentations and aids in phase retardation (PR) measurements. Previous studies have shown PR's effectiveness in identifying sub-clinical keratoconus (KC) in asymmetric cases. Thus, this study aims to assess PR distribution in thick corneas with and without KC. METHODS: In this retrospective and cross-sectional study, 45 thick corneas from 30 Asian-Indian subjects, categorized into healthy (n = 26) and KC (n = 19) groups were analyzed. All eyes underwent standard clinical evaluations, tomographic assessments, and corneal biomechanics measurements. PR and individual layer thicknesses were measured using custom-designed ultrahigh-resolution PS-OCT. PR en-face maps were generated. Individual layer thicknesses and PR analysis was conducted across multiple zones, extending up to 8-10 mm in diameter. All eyes in the study had not undergone interventions, received topical medications, or had previous corneal disease history. RESULTS: Significant differences were found in spherical and cylindrical powers, keratometry, pachymetry, and biomechanical indices (all P < 0.01). Thickness profiles from PS-OCT showed significant differences in the 4-8 mm zones only. Bowman's layer thickness significantly differed only in the central 2 mm zone (P = 0.02). The median PR values showed marginal differences in the central 2 mm zone (P = 0.0565). Additionally, there were significant differences observed in the 2-4 mm and 4-6 mm zones (P = 0.0274 and P = 0.0456, respectively). KC eyes exhibited an atypical PR distribution and corneal thinning, while normal eyes maintained a uniform Bowman's layer thickness and PR maps with larger areas of higher PR. CONCLUSION: The study revealed distinctive PR distribution in thick corneas among healthy and KC groups. Using an ultrahigh-resolution PS-OCT the significance of Bowman's layer thickness in these groups was also emphasized. The study offered potential improvements in clinical diagnostics by enhancing our understanding of corneal structure and its altered function.

Vitamin D and eye: Current evidence and practice guidelines.

Vitamin D is a steroid hormone that has widespread role in human physiology, not only in the maintenance of calcium homeostasis but also in immunomodulation, cellular differentiation, and proliferation. The immunomodulatory effects of vitamin D are well known and are applicable to the ocular surface immune cells and structural cells. The role of vitamin D in ocular surface conditions such as dry eye disease (DED), keratoconus (KC), and post-surgical outcomes has received widespread and well-deserved attention. Vitamin D supplementation is shown to improve DED clinically as well as in experimental models. The anti-inflammatory properties may be crucial in the treatment of ocular surface conditions such as DED and KC. Vitamin D plays a multifaceted role in corneal wound healing with its anti-inflammatory and extracellular matrix remodeling properties. In this review, we discuss how to approach patients with DED and those undergoing refractive surgery with the available basic and clinical knowledge on the role of vitamin D in these conditions. We aim to highlight the importance of clinically harnessing vitamin D-mediated natural immuno-inflammatory modulation in combination with currently available standard of care strategies to reduce the morbidity and disease duration associated with ocular surface diseases.

Hormones and dry eye disease.

The endocrine system influences all tissues and cells in the human body. The ocular surface is constantly exposed to circulating hormones and expresses their specific receptors. Dry eye disease (DED) is a disorder with multifactorial etiology, and endocrine anomalies are one of the inciting factors. The endocrine anomalies that cause DED include physiological conditions such as menopause, menstrual cycle variations, pathologies such as polycystic ovarian syndrome, androgen resistance, iatrogenic conditions such as contraceptive use, and antiandrogen treatment. This review highlights the status of these hormones in DED along with the mechanism of action of different hormones on the ocular surface structures and the clinical implications of these effects. The influence of androgens, estrogens, and progesterone on the ocular surface tissues, and the implications of androgen-deficient states in DED are also discussed. The physiological and pathological effects of menopause and sex hormone replacement therapy are discussed. The effects of insulin and insulin resistance on the ocular surface and DED, and the growing potential of topical insulin therapeutics for DED are mentioned. Thyroid-associated ophthalmopathy, its impact on the ocular surface, and the tissue effects of thyroid hormone in the context of DED are reviewed. Finally, the potential role of hormonal therapeutics in the management of DED has also been discussed. The compelling evidence suggests that it would be clinically beneficial to consider the possibility of hormonal imbalances and their impact while treating patients with DED.

Nexus of ocular motility and dry eye.

Purpose: To evaluate the effectiveness of vision therapy (VT) in patients with chronic presumed refractory dry eye disease (DED) and concurrent nonstrabismic binocular vision anomalies (NSBVAs). To propose an algorithmic approach to manage patients with refractory DED. Methods: Thirty-two patients with chronic (>1 year) presumed refractory DED and NSBVA were prospectively evaluated. The baseline dry eye evaluation and comprehensive orthoptic evaluation were done. VT was administered by a trained orthoptist for 2 weeks. The binocular vision (BV) parameters and percentage subjective improvement were assessed after the VT. Results: On evaluation, 12 patients (37.5%) had both DED and NSBVA, and 20 patients (62.5%) had only NSBVA. Twenty-nine patients (90.62%) showed significant improvement in BV parameters following VT. Binocular near point of accommodation (median, range) improved from 17 (8-40) to 12 (5-26) mm (P value < 0.0001), and near point of convergence (median, range) improved from 6 (3-33) to 6 (5-14) (P value 0.004) with VT. Thirty-one patients (96.87%) reported symptomatic improvement after VT, and 62.5% of these showed more than 50% improvement in symptoms. Conclusion: The present study confirms the beneficial role of VT in the treatment of patients with DED with concurrent NSBVA. It is essential to diagnose and treat NSBVA in patients with DED to ensure complete relief of symptoms and patient satisfaction. As there is a significant overlap between symptoms of dry eye disease and that of NSBVA, a complete orthoptic evaluation is recommended in all patients presenting with refractory dry eye disease related symptoms.

Modulation of mucin secretion using combined polyethylene glycol-propylene glycol topical formulation in a hyperosmotic stress-based explant model.

Purpose: Ocular surface discomfort and dry eye disease are caused by a dysfunctional tear film. The efficacy of lubricating eye drops on the human eye is known, but the compositions may show differential effects on rescuing the tear film. Mucins form a critical layer of the tear film, a reduction of which may be causative for ocular surface conditions. Therefore, it is essential to develop relevant human-derived models to test mucin production. Methods: Human corneoscleral rims were obtained from a healthy donor (n = 8) post-corneal keratoplasty and cultured in DMEM/F12 media. Hyperosmolar stress mimicking dry eye disease was induced by exposing the corneoscleral rim tissues to +200 mOsml NaCl-containing media. The corneoscleral rims were treated with polyethylene glycol-propylene glycol (PEG-PG)-based topical formulation. Gene expression analysis was performed for NFAT5, MUC5AC, and MUC16. Secreted mucins were measured by enzyme-linked immunosorbent assay (ELISA) (Elabscience, Houston, TX, USA) for MUC5AC and MUC16. Results: The corneoscleral rims responded to hyperosmolar stress by upregulating NFAT5, a marker for increased osmolarity, as observed in the case of dry eye disease. The expression of MUC5AC and MUC16 was reduced upon an increase in hyperosmotic stress. The corneoscleral rim tissues showed induction of MUC5AC and MUC16 expression upon treatment with PEG-PG topical formulation but did not show significant changes in the presence of hyperosmolar treatments. Conclusion: Our findings showed that PEG-PG-based topical formulation slightly alleviated hyperosmolar stress-induced decrease in MUC5AC and MUC16 gene expression that is encountered in DED.

Universal architecture of corneal segmental tomography biomarkers for artificial intelligence-driven diagnosis of early keratoconus.

AIMS: To develop a comprehensive three-dimensional analyses of segmental tomography (placido and optical coherence tomography) using artificial intelligence (AI). METHODS: Preoperative imaging data (MS-39, CSO, Italy) of refractive surgery patients with stable outcomes and diagnosed with asymmetric or bilateral keratoconus (KC) were used. The curvature, wavefront aberrations and thickness distributions were analysed with Zernike polynomials (ZP) and a random forest (RF) AI model. For training and cross-validation, there were groups of healthy (n=527), very asymmetric ectasia (VAE; n=144) and KC (n=454). The VAE eyes were the fellow eyes of KC patients but no further manual segregation of these eyes into subclinical or forme-fruste was performed. RESULTS: The AI achieved an excellent area under the curve (0.994), accuracy (95.6%), recall (98.5%) and precision (92.7%) for the healthy eyes. For the KC eyes, the same were 0.997, 99.1%, 98.7% and 99.1%, respectively. For the VAE eyes, the same were 0.976, 95.5%, 71.5% and 91.2%, respectively. Interestingly, the AI reclassified 36 (subclinical) of the VAE eyes as healthy though these eyes were distinct from healthy eyes. Most of the remaining VAE (n=104; forme fruste) eyes retained their classification, and were distinct from both KC and healthy eyes. Further, the posterior surface features were not among the highest ranked variables by the AI model. CONCLUSIONS: A universal architecture of combining segmental tomography with ZP and AI was developed. It achieved an excellent classification of healthy and KC eyes. The AI efficiently classified the VAE eyes as 'subclinical' and 'forme-fruste'.

Impact of crossplay between ocular aberrations and depth of focus in topo-guided laser-assisted in situ keratomileusis outcomes.

Purpose: To develop a nomogram in cases with mismatch between subjective and Topolyzer cylinder, and based on the magnitude of the mismatch, customize a treatment plan to attain good visual outcomes post-laser-assisted in situ keratomileusis (LASIK) surgery. Methods: The patients were evaluated preoperatively using corneal tomography with Pentacam. Five optimal corneal topography scans were obtained from the Topolyzer Vario were used for planning the LASIK treatment. For the nomogram purpose, the patients were divided into three categories based on the difference between the subjective cylinder and Topolyzer (corneal) cylinder. The first group (group 1) consisted of eyes of patients, where the difference was less than or equal to 0.4 D. The second group (group 2) consisted of eyes, where the difference was more than 0.4 D and the subjective cylinder was lesser than the Topolyzer cylinder. The third group (group 3) included eyes where the difference was more than 0.4 D but the subjective cylinder was greater than the Topolyzer cylinder. LASIK was performed with the WaveLight FS 200 femtosecond laser and WaveLight EX500 excimer laser. Assessment of astigmatism correction for the three groups was done using Aplins vector analysis. For comparison of proportions, Chi-square test was used. A P value less than 0.05 was considered statistically significant. Results: The UDVA was statistically significantly different when compared between groups 1 and 2 (P = 0.02). However, the corrected distance visual acuity (CDVA) was similar among all the three groups (P = 0.1). Group 3 showed an increase of residual cylinder by -0.25 D, which was significant at intermediate and near reading distances (P < 0.05). Group 3 showed significantly higher target-induced astigmatism (TIA) compared to groups 1 and 2 (P = 0.01). The mean surgically induced astigmatism (SIA) was the least in group 2, which was statistically significant (P < 0.01). Conclusion: The outcomes for distance vision using our nomogram postoperatively were excellent, but further refinement for improving the near vision outcomes is required.

Role of artificial intelligence in determining factors impacting patients' refractive surgery decisions.

Purpose: To create a predictive model using artificial intelligence (AI) and assess if available data from patients' registration records can help in predicting definitive endpoints such as the probability of patients signing up for refractive surgery. Methods: This was a retrospective analysis. Electronic health records data of 423 patients presenting to the refractive surgery department were incorporated into models using multivariable logistic regression, decision trees classifier, and random forest (RF). Mean area under the receiver operating characteristic curve (ROC-AUC), sensitivity (Se), specificity (Sp), classification accuracy, precision, recall, and F1-score were calculated for each model to evaluate performance. Results: The RF classifier provided the best output among the various models, and the top variables identified in this study by the RF classifier excluding income were insurance, time spent in the clinic, age, occupation, residence, source of referral, and so on. About 93% of the cases that did undergo refractive surgery were correctly predicted as having undergone refractive surgery. The AI model achieved an ROC-AUC of 0.945 with an Se of 88% and Sp of 92.5%. Conclusion: This study demonstrated the importance of stratification and identifying various factors using an AI model which could impact patients' decisions while selecting a refractive surgery. Eye centers can build specialized prediction profiles across disease categories and may allow for the identification of prospective obstacles in the patient's decision-making process, as well as strategies for dealing with them.

Simultaneous Topography-guided Custom Ablation With Corneal Cross-linking for Keratoconus: 10-Year Prospective Outcomes.

PURPOSE: To assess 10-year visual and tomographic outcomes of topography-guided custom ablation (T-CAT) with corneal cross-linking (CXL) in eyes with keratoconus. METHODS: T-CAT with CXL was performed in 600 eyes (522 patients). Based on the T-CAT ablation plan, the theoretical maximum ablation depth was 50 µm after epithelium removal. After ablation, accelerated corneal cross-linking (CXL) was performed in the central 8-mm zone (9 mW/cm2 for 10 minutes in "epi-off" mode). The visual acuity and tomography were assessed. RESULTS: There was significant improvement in uncorrected (P = .001) and corrected (P = .001) distance visual acuity after the procedure. Keratometry, root mean square lower order aberrations and higher order aberrations, defocus, coma 90°, and spherical aberration reduced significantly after surgery at 10 years of follow-up (P < .005). All Pentacam (Oculus Optikgerate GmbH) tomographic variables showed significant changes indicating regularization after T-CAT (P < .005). Flattening of greater than 5.00 diopters in maximum keratometry was noted in 6 eyes (1%). Two of 600 eyes progressed postoperatively and required repeat CXL. CONCLUSIONS: T-CAT plus CXL is a safe and effective technique even in the long term for regularizing the anterior corneal surface with significant visual improvement and reduction in higher order corneal aberrations. [J Refract Surg. 2023;39(11):759-766.].

Role of in vivo confocal microscopy in dry eye disease and eye pain.

Dry eye disease is known to have a lot of variability in presentation with overlapping subtypes. Understanding the pathology of this condition will guide therapeutic options. In vivo confocal microscopy is a diagnostic and imaging modality that provides high magnification and high-resolution images of all layers of the cornea and ocular surface. Various structures in the cornea and their alterations due to dry eye have been imaged. The impact of the tear film instability, inflammation, and altered homeostasis on the corneal epithelium, nerves, keratocytes, and dendritic cells have been evaluated across different studies. In addition, key features of IVCM in patients with neuropathic pain have been highlighted in this paper.

Ion channels in dry eye disease.

Dry eye disease (DED) which affects millions of people worldwide is an ocular surface disease that is strongly associated with pain, discomfort, and visual disturbances. Altered tear film dynamics, hyperosmolarity, ocular surface inflammation, and neurosensory abnormalities are the key contributors to DED pathogenesis. The presence of discordance between signs and symptoms of DED in patients and refractoriness to current therapies in some patients underpin the need for studying additional contributors that can be modulated. The presence of electrolytes or ions including sodium, potassium, chloride, bicarbonate, calcium, and magnesium in the tear fluid and ocular surface cells contribute to ocular surface homeostasis. Ionic or electrolyte imbalance and osmotic imbalance have been observed in DED and feed-forward interaction between ionic imbalances and inflammation alter cellular processes in the ocular surface resulting in DED. Ionic balances in various cellular and intercellular compartments are maintained by dynamic transport via ion channel proteins present in cell membranes. Hence, alterations in the expression and/or activity of about 33 types of ion channels that belong to voltage-gated channels, ligand-gated channels, mechanosensitive ion channel, aquaporins, chloride ion channel, sodium-potassium-chloride pumps or cotransporters have been investigated in the context of ocular surface health and DED in animal and/or human subjects. An increase in the expression or activity of TRPA1, TRPV1, Nav1.8, KCNJ6, ASIC1, ASIC3, P2X, P2Y, and NMDA receptor have been implicated in DED pathogenesis, whereas an increase in the expression or activity of TRPM8, GABAA receptor, CFTR, and NKA have been associated with resolution of DED.

Autophagy in dry eye disease: Therapeutic implications of autophagy modulators on the ocular surface.

Dry eye disease (DED) is a chronic ocular surface disorder, associated with inflammation, which can cause severe morbidity, visual compromise, and loss of quality of life, affecting up to 5-50% of the world population. In DED, ocular surface damage and tear film instability due to abnormal tear secretion lead to ocular surface pain, discomfort, and epithelial barrier disruption. Studies have shown the involvement of autophagy regulation in dry eye disease as a pathogenic mechanism along with the inflammatory response. Autophagy is a self-degradation pathway in mammalian cells that reduces the excessive inflammation driven by the secretion of inflammatory factors in tears. Specific autophagy modulators are already available for the management of DED currently. However, growing studies on autophagy regulation in DED might further encourage the development of autophagy modulating drugs that reduce the pathological response at the ocular surface. In this review, we summarize the role of autophagy in the pathogenesis of dry eye disease and explore its therapeutic application.

Patient stratification using point of care biomarkers in dry eye disease.

With changes in lifestyle, such as the increasing use of digital screens and rising demand for refractive surgery, dry eye disease has become increasingly prevalent in recent times. While we are equipped with a number of diagnostic modalities and a myriad of treatment forms, ranging from topical medication to procedural therapies, the condition remains an enigma in terms of varied patient satisfaction. An understanding of the molecular basis of a disease may open up new avenues in the customization of its treatment. We attempt to simplify this in the form of a stepwise protocol to incorporate biomarker assays in dry eye management.