Elevated Neutrophils and reduced NK cells are associated with altered tear molecular signatures and clinical sequelae of chronic ocular Stevens-Johnson Syndrome.

PURPOSE: Stevens-Johnson syndrome (SJS) is characterised as an immuno-inflammatory condition with potentially blinding ocular sequelae. Therefore, we have investigated the ocular surface immune cell profile and correlated it with secreted tear molecular factors and clinical ocular sequelae in SJS patients. METHODS: 21 patients (42 eyes) with chronic ocular SJS and 16 healthy controls (20 eyes) were included in the study. Severity, types of keratopathies and ocular surface(OS) manifestations were determined. OS wash samples from study subjects were used to determine the status of 13 immune cell subsets using flow cytometry. Levels of 42 secreted immuno-inflammatory factors were measured by flow cytometry-based multiplex ELISA in tear samples. RESULTS: Neutrophils (Total, activated), neutrophils/NK cells ratio, neutrophils/T cells ratio were significantly (p<0.05) elevated in SJS, while, proportions of T cells and NKT cells were significantly lower in SJS patients. Positive association between neutrophils and chronic ocular surface complication score (COCS) was observed, whereas, a negative association was noted between NK cells and COCS. Tear fluid levels of IL-6, IL-8, IL-18, IFNα/ß/γ, TNFα, LIF, IL-8, HGF, sTNFR-I, NGAL, Granzyme, Perforins, MMP9/TIMP1 ratio were significantly higher in SJS. Loss of Limbal niche correlated significantly with immune profile and clinical sequelae. Increased neutrophils, decreased NK cells and specific set of altered secreted immuno-inflammatory mediators including bFGF, and IL-8 were observed in SJS patients with different types of keratopathies compared to those without keratopathy. CONCLUSION: Distinct ocular surface immune profile variations were observed to correlate with clinical stages of chronic ocular SJS. Our findings uncover novel mechanisms and potential for targeted therapy in chronic ocular SJS patients.

Safety of an Intracameral Fixed Combination for Mydriasis and Intraocular Anaesthesia During Cataract Surgery.

Purpose: To compare the safety of a standardized, commercially available intracameral combination of mydriatics and anesthetic (ICMA) with a reference topical mydriatic regimen for cataract surgery. Patients and Methods: The safety results from two international, randomized, controlled clinical studies were combined to compare ICMA at the beginning of cataract surgery (ICMA group) to the reference topical mydriatic regimen (reference group). Data were collected on ocular and systemic adverse events, corneal and anterior chamber examination, endothelial cell density, retinal thickness and visual acuity. Analysis was performed on a pooled safety set from both studies, preoperatively and up to 1 month postoperatively. Results: 342 patients received ICMA and 318 the reference topical regimen. Ocular adverse events were reported in 17.0% of patients in the ICMA group and 18.6% in the reference group. No difference was shown between groups in endothelial cell density (2208 ± 498 cells/mm2 for ICMA group versus 2241 ± 513 cells/mm2 for the reference group; p=0.547) and retinal thickness (change from baseline less than 50 µm in 94.7% versus 95.0% of patients, respectively) at 1 month postoperatively. At 1-day post-surgery, less patients in the ICMA group had moderate or severe (Grades 2 and 3) superficial punctate corneal staining (3.9% versus 7.0% for the reference group; p=0.064). Postoperatively, some ocular symptoms were also less frequently reported in the ICMA group. Best-corrected visual acuity increased in 96.0% of patients in the ICMA group and 95.8% in the reference group at 1 month. Conclusion: ICMA injection at the beginning of cataract surgery was demonstrated to be safe and may also provide perioperative and postoperative advantages over the standard topical mydriatic regimen.

Retrospective assessment of accuracy of nine intraocular lens power calculation formulae in eyes with axial myopia.

PURPOSE: To compare the accuracy of nine conventional and newer-generation formulae in calculating intraocular lens power in eyes with axial myopia. SETTING: Tertiary eye care center, Bengaluru, India. DESIGN: Retrospective cross-sectional, comparative study conducted in India. METHODS: Patients undergoing uneventful phacoemulsification in eyes with axial length >26 mm were included. Preoperative biometry was done using Lenstar LS 900 (Haag-Streit AG, Switzerland). Single eye of patients undergoing bilateral implantation was randomly selected. Optimized lens constants were used to calculate the predicted postoperative refraction of each formula, which was then compared with the actual refractive outcomes to give the prediction errors, following which subgroup analysis was performed. The Kane formula, Barrett universal II, Emmetropia Verifying Optical (EVO) 2.0, Hill Radial Basis Function (Hill RBF) 3.0, Olsen formula, along with Wang Koch-adjusted four formulae, that is, Sanders Retzlaff Kraff/Theoretical (SRK/T), Holladay 1, Haigis, and Hoffer Q formula, were compared for intraocular lens power calculations. RESULTS: One hundred and sixty-five eyes that fulfilled all the inclusion criteria were studied. Hill RBF 3.0 had the lowest mean and median absolute prediction errors (0.355 and 0.275, respectively) compared to all formulas. In subgroup analysis (26-28, >28-30, and >30 mm), significant difference was seen only in extremely long eyes (>30 mm). The Hill RBF 3.0 formula generated the maximum percentage of eyes with refractive errors within ±0.25, ±0.5, ±0.75, and ±1 D (46%, 76.2%, 89.9%, and 95.8%, respectively). CONCLUSION: This is the first study evaluating all the formulas exclusively in the myopic eyes. Hill RBF 3 was found to be superior in accuracy to all other formulas.

Suboptimal visual outcome after femto-LASIK ablation in a high myopic patient.

A 28-year-old nurse had an aberration-free femto-laser in situ keratomileusis (LASIK) performed for her myopia of -6.25 -0.50 × 096 and -6.75 -0.50 × 175 in the right and left eye, respectively. Corrected distance visual acuity (CDVA) preoperatively was 20/16. Preoperatively, there were no abnormalities on Scheimpflug imaging, and a pachymetry of 585 µm was measured in both eyes. Flap thickness was 115 µm. The patient was quite nervous during the surgery. Since the surgery, her uncorrected distance visual acuity (UDVA) and CDVA are suboptimal at 20/30 and 20/20 in the right eye, and 20/20 and 20/16 in the left eye. 3 months postoperatively, there is a stable manifest refraction of +0.25 -1.25 × 030 and +0.25 -0.00 × 0. The keratometric astigmatism in the Scheimpflug imaging is 1.2 diopter (D) × 114 and 0.4 D × 78 in the right and left eyes, respectively (FIgures 1 and 2). Thinnest pachymetry is 505 µm and 464 µm in the right and left eye, respectively. Her wavefront analysis shows refraction in a 6 mm zone of -0.99 -1.22 × 32 and -0.91 -0.36 × 136. The cycloplegic refraction is 1.25 -1.00 × 023 and +1.00 -0.25 × 006 (Figures 3 and 4). What is the cause of the suboptimal visual outcome in this case? What would be your treatment strategy to improve visual outcome?

Cost-effectiveness of the ADVISE trial: An intraoperative OCT protocol in DMEK surgery.

The intraoperative optical coherence tomography (iOCT) is recently introduced in Descemet membrane endothelial keratoplasty (DMEK) surgery, which aims to increase clinical performance and surgery safety. However, the acquisition of this modality is a substantial investment. The objective of this paper is to report on the cost-effectiveness of an iOCT-protocol in DMEK surgery with the Advanced Visualization in Corneal Surgery Evaluation (ADVISE) trial. This cost-effectiveness analysis uses data 6 months postoperatively from the multicentre prospective randomized clinical ADVISE trial. Sixty-five patients were randomized to usual care (n = 33) or the iOCT-protocol (n = 32). Quality-Adjusted Life Years (EQ-5D-5L), Vision-related Quality of Life (NEI-VFQ-25) and self-administered resources questionnaires were administered. Main outcome is the incremental cost-effectiveness ratio (ICER) and sensitivity analyses. The iOCT protocol reports no statistical difference in ICER. For the usual care group compared with the iOCT protocol, respectively, the mean societal costs are €5027 compared with €4920 (Δ€107). The sensitivity analyses report the highest variability on time variables. This economic evaluation learned that there is no added value in quality of life or cost-effectiveness in using the iOCT protocol in DMEK surgery. The variability of cost variables depends on the characteristics of an eye clinic. The added value of iOCT could gain incrementally by increasing surgical efficiency, and aiding in surgical decision-making.

Using adaptive optics to optimize the spherical aberration of eyes implanted with EDOF and enhanced monofocal intraocular lenses.

PURPOSE: To assess the effect of change in ocular spherical aberration (SA) with adaptive optics on visual acuity (VA) at different defocus after implantation of extended depth-of-focus (EDOF) and enhanced monofocal intraocular lenses (IOLs). SETTINGS: Narayana Nethralaya Eye Hospital, Bangalore, India. DESIGN: Prospective, longitudinal, observational. METHODS: 80 eyes (40 patients) that had cataract surgery were included in the study. 40 eyes were implanted with Eyhance EDOF IOLs and the remaining with Vivity EDOF IOLs. Baseline ocular aberrations were measured with a visual adaptive optics aberrometer, then the optimal SA was determined by increasing it in steps of -0.01 µm up to -0.1 µm until the maximum improvement in near distance VA was observed for a given eye. Then the defocus curve for each eye was measured after modifying the ocular SA by magnitude equal to optimal SA. RESULTS: Most of the eyes accepted a negative induced SA of -0.05 µm (Eyhance group: 67.6%; Vivity group, 45.2%). In the Eyhance group (dominant eyes), VA improved at -2 diopters (D) ( P < .02) only and degraded at 0 D, +0.5 D, and +1 D defocus ( P < .05). In the Vivity group, the VA remained unchanged at all defocus ( P > .05). In the Eyhance group (nondominant eyes), VA improved at -3.5 D defocus only and degraded at +1.5 D and +2 D defocus ( P < .05). In the Vivity group, VA improved at -2.5 D defocus ( P < .05) only. CONCLUSIONS: A negative induced SA of -0.05 µm in implanted eyes was optimal for a slight improvement in distance-corrected near and intermediate VA without any significant decrease in baseline distance-corrected VA.

Tear Fluid Inflammatory Proteome Analysis Highlights Similarities Between Keratoconus and Allergic Conjunctivitis.

Purpose: Keratoconus is characterized by the progressive thinning of the cornea, which leads to a cone-like appearance of the eye over time. Although conventionally defined as a noninflammatory condition, a number of recent studies have associated keratoconus (KC) with allergic conjunctivitis (AC) based on clinical parameters. This study aimed to consolidate this association by performing a proteomic analysis of tear fluid from patients with keratoconus and/or allergic conjunctivitis. Methods: Of 51 patients, 17 were diagnosed with KC, 17 were diagnosed with AC, and 17 were diagnosed with both KC and AC (combined). Nine of 34 patients with KC had a progressive form of the disease. Tear fluid samples (n = 51, one eye per patient) were collected by the Schirmer's strips. Tear proteins were extracted from the Schirmer's strips. Proteomic profiling of 384 inflammatory proteins was assessed by a multiplex proximity extension assay (Olink Explore 384 Inflammation Panel I). Results: A total of 384 inflammatory proteins were measured. Two hundred seventy-two of the 384 proteins passed stringent data cleaning and were compared among the patient groups. Compared to the 2 other groups, LGALS9 was upregulated uniquely in KC, whereas FGF19, PDGFB, HPCAL1, OSM, and FCAR were downregulated in KC. Similarly, TNFRSF4 and CCL13 were specifically upregulated in AC, whereas ectodysplasin A receptor (EDAR) was uniquely downregulated in AC. Conclusions: High-throughput proteomic profiling of tear fluid confirms the association between KC and AC on a molecular level and raise the importance of redefining KC as an inflammatory condition.

Complications during elective cataract surgery: did the COVID-19 lockdown affect outcomes of ophthalmic surgery?

PURPOSE: One of the many consequences of the COVID-19 pandemic was a worldwide lockdown of ophthalmic surgery procedures for several months in 2020. The present study aims to answer the following question: does an intermission of cataract surgery for two months cause an increase in complication rates? METHODS: In this retrospective clinical chart review, data was taken from Dutch cataract complication registration database that contains pre-, intra- and postoperative information of patients that underwent cataract surgery in the Netherlands. The amount as well as type of complications were extracted before and after the eight weeks surgical intermission period (SIP): six weeks before (SIP-6) and six weeks after this period (SIP+6) for the years 2016-2020. RESULTS: A significant decrease in complication rates was found between SIP-6 and SIP+6 in 2020. When SIP+6 2020 is compared to SIP+6 2019, a significant reduction is found. Overall, a downward trend in complication rates was observed in the period 2016-2020. CONCLUSION: A two-months intermission of performing elective cataract surgery does not cause an increase in complications. In contrast, we observe a reduction of postoperative complications. This implicates that refraining from cataract surgery for two months might not compromise operative skills. The possible downward trend over the years can be partially explained by improved training, education and equipment, as well as an increased use of intracameral antibiotics during operation. Possible explanations for the reduction of complications after lockdown could be decreased time pressure as a consequence of a reduced number of operations at the restart of surgeries, and heightened awareness and cautiousness when resuming the operations.

Accuracy of Toric Intraocular Lens Calculations Using Estimated Versus Measured Posterior Corneal Astigmatism.

PURPOSE: To compare the prediction accuracy of toric intraocular lens calculations using estimated vs measured posterior corneal astigmatism (PCA). DESIGN: Retrospective case series. METHODS: A total of 110 eyes of 110 patients with uncomplicated toric intraocular lens implantation were included in this study. Predicted postoperative refractive astigmatism was calculated with the Barrett Toric Calculator using the estimated PCA (E-PCA), the measured IOLMaster 700 PCA (I-PCA), and the measured Pentacam PCA (P-PCA). Refractive astigmatism prediction errors (RA-PEs), including their trimmed (tr-) centroid (mean vector), spread (precision), tr-mean absolute RA-PE (accuracy), and percentage within a certain threshold, were determined using vector analysis and compared between groups. SETTING: University Eye Clinic, Maastricht University Medical Center+, the Netherlands. RESULTS: The tr-centroid RA-PEs of the E-PCA (0.02 diopter [D] at 82.2°), the I-PCA (0.08 D at 35.5°), and the P-PCA (0.09 D at 69.1°) were significantly different from each other (P < .01), but not significantly different from zero (P = .75, P = .05, and P = .05, respectively). The E-PCA had the best precision (tr-mean 0.40 D), which was not significantly lower than the I-PCA (0.42 D, P = .53) and P-PCA (0.43 D, P = .06). The E-PCA also had the best accuracy (0.40 D), which was not significantly different from the I-PCA (0.42 D, P = .26) and significantly better than the P-PCA (0.44 D, P < .01). The precision and accuracy of the I-PCA did not significantly differ from those of the P-PCA. There were no statistically significant differences in the percentage of eyes within a certain absolute RA-PE threshold. CONCLUSIONS: The Barrett Toric Calculator using the E-PCA, I-PCA, or P-PCA showed a comparable prediction of postoperative refractive astigmatism in standard clinical practice.

Allogeneic Serum Eye Drops: A Randomized Clinical Trial to Evaluate the Clinical Effectiveness of Two Drop Sizes.

INTRODUCTION: Allogeneic serum from blood donors is starting to be used to treat patients with dry eye disease (DED). However, the optimal dose is not known. We therefore aimed to evaluate the clinical efficaciousness and user-friendliness of micro-sized versus conventional-sized allogeneic serum eye drops (SEDs). METHODS: In a randomized trial, patients with DED first receive micro-sized SEDs (7 µl/unit) for 1 month, followed by a 1-month washout, before receiving conventional-sized SEDs (50 µl/unit) for 1 month; or vice versa. The primary endpoint was the Ocular Surface Disease Index (OSDI) score. Secondary endpoints were tear break-up time (TBT), tear production (TP), and presence of corneal punctate lesions (CP). The user-friendliness of both application systems was also compared. A linear mixed model for cross-over design was applied to compare both treatments. RESULTS: Forty-nine patients completed the trial. The mean OSDI score significantly improved from 52 ± 3 to 41 ± 3 for micro-sized SEDs, and from 54 ± 3 to 45 ± 3 for conventional-sized SEDs. Non-inferiority (margin = 6) of micro-sized SEDs was established. We demonstrate a significant improvement for TBT in case of conventional-sized SEDs and for CP in both treatment groups. TP trended towards an improvement in both treatment groups. The user-friendliness of the conventional drop system was significantly higher. CONCLUSIONS: For the first time, non-inferiority of micro-sized allogeneic SEDs was established. The beneficial effect of both SED volumes was similar as measured by the OSDI score. Although user-friendliness of the micro drop system was significantly lower, it is an attractive alternative as it saves valuable donor serum. TRIAL REGISTRATION: ClinicalTrials.gov (NCT03539159).

Minimum Corneal Diameter and Anterior Steep Axis Curvature Share the Same Meridian: A Novel Finding.

PURPOSE: To define the external scleral sulcus (ESS) on a Scheimpflug image and use it for a morphometric analysis of corneal diameter (CD). DESIGN: Retrospective, cross-sectional study of pediatric Asian-Indian eyes. METHODS: One random eye of 353 subjects between 5 and 18 years underwent 25-scan Pentacam HR imaging. For all scans, densitometry values along the anterior corneal edge were recorded and differentiated. The peaks on the differentiated curve were chosen as the ESS points, and this distance between them was called CD. Vertical (vCD), maximum (maxCD), minimum (minCD) CD and their meridians were defined. Multiple regression models (MRMs) with CD and other Pentacam parameters were built to predict astigmatism and its axis, mean keratometry (Kmean), and Belin/Ambrósio enhanced ectasia display deviation (BAD-D). MRMs were validated using intraclass correlation coefficient (ICC). Estimated horizontal CD (hCD) was validated against digital caliper measurement using ICC. RESULTS: The ICC (95% CI) between caliper and hCD was 0.96 (0.93, 0.97). MRM predictions (P < .001) used CD parameters, anterior chamber depth, corneal volume and distance from the corneal thinnest location to apex. These predictions achieved an ICC of 0.34 (0.18, 0.46), 0.82 (0.78, 0.86), 0.87 (0.84, 0.89), and 0.81 (0.76, 0.84), respectively. The astigmatism axis prediction depended on the minCD and maxCD meridians. Its within-subject SD (4.97°) was less than 2 consecutive Pentacam scan angles (7.2°). CONCLUSIONS: The CD metric strongly correlated with the astigmatism axis, keratometry, and BAD-D. Its spatial description may be significant in corneal treatment planning and disease diagnoses.

Measuring quality of vision including negative dysphotopsia.

PURPOSE: To adapt the Quality of Vision Questionnaire (QoV) for measuring negative dysphotopsia and to validate the original and modified versions in the Dutch population. METHODS: The QoV was translated into Dutch according to standardized methodology. Negative dysphotopsia items were constructed based on focus group interviews, literature review and clinical data. The questionnaire was completed by 404 subjects, including contact lens wearers, patients with cataract and after cataract surgery (95.5% with a monofocal, 4.5% with a multifocal intraocular lens). Rasch analysis was applied for evaluation of reliability and validity of the original QoV and modified version, Negative Dysphotopsia QoV (ND-QoV). RESULTS: The frequency, severity and bothersome scales of the QoV and ND-QoV demonstrated good measurement precision, good fit statistics for all but one item, but significant mistargeting of more than one logit. Item estimations were stable across the study groups and scales were unidimensional with more than 50% of variance explained by the measurements. There was a positive correlation between questionnaire scores and best corrected visual acuity (r = 0.3, p < 0.01). The quality of vision measured by all three scales was significantly poorer (p < 0.01) in patients with negative dysphotopsia compared to asymptomatic pseudophakic patients. CONCLUSION: The Dutch version of the QoV questionnaire has shown good psychometric properties comparable to the native version as well as good reliability and validity. The addition of negative dysphotopsia items is a valuable modification for the reliable assessment of quality of vision in pseudophakic patients.

(Pre)diabetes and a higher level of glycaemic measures are continuously associated with corneal neurodegeneration assessed by corneal confocal microscopy: the Maastricht Study.

AIMS/HYPOTHESIS: To assess the associations between glucose metabolism status and a range of continuous measures of glycaemia with corneal nerve fibre measures, as assessed using corneal confocal microscopy. METHODS: We used population-based observational cross-sectional data from the Maastricht Study of N=3471 participants (mean age 59.4 years, 48.4% men, 14.7% with prediabetes, 21.0% with type 2 diabetes) to study the associations, after adjustment for demographic, cardiovascular risk and lifestyle factors, between glucose metabolism status (prediabetes and type 2 diabetes vs normal glucose metabolism) plus measures of glycaemia (fasting plasma glucose, 2 h post-load glucose, HbA1c, skin autofluorescence [SAF] and duration of diabetes) and composite Z-scores of corneal nerve fibre measures or individual corneal nerve fibre measures (corneal nerve bifurcation density, corneal nerve density, corneal nerve length and fractal dimension). We used linear regression analysis, and, for glucose metabolism status, performed a linear trend analysis. RESULTS: After full adjustment, a more adverse glucose metabolism status was associated with a lower composite Z-score for corneal nerve fibre measures (ß coefficients [95% CI], prediabetes vs normal glucose metabolism -0.08 [-0.17, 0.03], type 2 diabetes vs normal glucose metabolism -0.14 [-0.25, -0.04]; linear trend analysis showed a p value of 0.001), and higher levels of measures of glycaemia (fasting plasma glucose, 2 h post-load glucose, HbA1c, SAF and duration of diabetes) were all significantly associated with a lower composite Z-score for corneal nerve fibre measures (per SD: -0.09 [-0.13, -0.05], -0.07 [-0.11, -0.03], -0.08 [-0.11, -0.04], -0.05 [-0.08, -0.01], -0.09 [-0.17, -0.001], respectively). In general, directionally similar associations were observed for individual corneal nerve fibre measures. CONCLUSIONS/INTERPRETATION: To our knowledge, this is the first population-based study to show that a more adverse glucose metabolism status and higher levels of glycaemic measures were all linearly associated with corneal neurodegeneration after adjustment for an extensive set of potential confounders. Our results indicate that glycaemia-associated corneal neurodegeneration is a continuous process that starts before the onset of type 2 diabetes. Further research is needed to investigate whether early reduction of hyperglycaemia can prevent corneal neurodegeneration.

Tear biomarkers for Alzheimer's disease screening and diagnosis (the TearAD study): design and rationale of an observational longitudinal multicenter study.

BACKGROUND: Alzheimer's disease (AD) is the most common cause of dementia, and due to increasing life expectancy the number of patients is expected to grow. The diagnosis of AD involves the use of biomarkers determined by an amyloid PET scan or cerebrospinal fluid analyses that are either invasive or expensive, and not available in each hospital, thus limiting their usage as a front-line screener. The TearAD study aims to use tear fluid as a potential source for AD biomarkers. In previous reports, we demonstrated that AD biomarkers amyloid-beta and tau, are measurable in tear fluid and are associated with disease severity and neurodegeration. This study aims to validate previous results in a larger cohort and evaluate the diagnostic accuracy of tear biomarkers to discriminate between individuals with and without neurodegeneration as determined by hippocampal atrophy. METHODS: The TearAD study is an observational longitudinal multi-center study that will enroll 50 cognitively healthy controls, 50 patients with subjective cognitive decline, 50 patients with mild cognitive impairment and 50 patients with AD dementia from the memory clinic. Participants will be examined at baseline, after one year, and after two years follow-up. Study assessments include neuropsychological tests and ophthalmic examination. All participants will receive a MRI scan, and a subset of the study population will undergo cerebral spinal fluid collection and an amyloid PET scan. Tear fluid will be collected with Schirmer strips and levels of Aß38, Aß40, Aß42, t-tau and p-tau in tear fluid will be determined using multiplex immunoassays. Blood samples will be collected from all participants. Images of the retina will be obtained with a standard, hyperspectral and ultra-wide field fundus camera. Additionally, macular pigment optical density will be measured with the macular pigment reflectometer, and cross-sectional images of the retina will be obtained through optical coherence tomography imaging. DISCUSSION: The TearAD study will provide insight into the potential diagnostic use of tear biomarkers as a minimally invasive and low cost tool for the screening and diagnosis of AD. TRIAL REGISTRATION: Retrospectively registered at clinicaltrials.gov (NCT05655793).

Artificial intelligence-based stratification of demographic, ocular surface high-risk factors in progression of keratoconus.

Purpose: The purpose of this study was to identify and analyze the clinical and ocular surface risk factors influencing the progression of keratoconus (KC) using an artificial intelligence (AI) model. Methods: This was a prospective analysis in which 450 KC patients were included. We used the random forest (RF) classifier model from our previous study (which evaluated longitudinal changes in tomographic parameters to predict "progression" and "no progression") to classify these patients. Clinical and ocular surface risk factors were determined through a questionnaire, which included presence of eye rubbing, duration of indoor activity, usage of lubricants and immunomodulator topical medications, duration of computer use, hormonal disturbances, use of hand sanitizers, immunoglobulin E (IgE), and vitamins D and B12 from blood investigations. An AI model was then built to assess whether these risk factors were linked to the future progression versus no progression of KC. The area under the curve (AUC) and other metrics were evaluated. Results: The tomographic AI model classified 322 eyes as progression and 128 eyes as no progression. Also, 76% of the cases that were classified as progression (from tomographic changes) were correctly predicted as progression and 67% of cases that were classified as no progression were predicted as no progression based on clinical risk factors at the first visit. IgE had the highest information gain, followed by presence of systemic allergies, vitamin D, and eye rubbing. The clinical risk factors AI model achieved an AUC of 0.812. Conclusion: This study demonstrated the importance of using AI for risk stratification and profiling of patients based on clinical risk factors, which could impact the progression in KC eyes and help manage them better.

Efficacy of customized corneal crosslinking versus standard corneal crosslinking in patients with progressive keratoconus (C-CROSS study): study protocol for a randomized controlled trial.

BACKGROUND: Keratoconus is a degenerative disorder of the cornea leading to a protrusion and thinning with loss of visual acuity. The only treatment to halt the progression is corneal crosslinking (CXL), which uses riboflavin and UV-A light to stiffen the cornea. Recent ultra-structural examinations show that the disease is regional and does not affect the entire cornea. Treating only the affected zone with CXL could be as good as the standard CXL, that treats the entire cornea. METHODS: We set up a multicentre non-inferiority randomized controlled clinical trial comparing standard CXL (sCXL) and customized CXL (cCXL). Patients between 16 and 45 years old with progressive keratoconus were included. Progression is based on one or more of the following changes within 12 months: 1 dioptre (D) increase in keratometry (Kmax, K1, K2); or 10% decrease of corneal thickness; or 1 D increase in myopia or refractive astigmatism, requiring corneal crosslinking. DISCUSSION: The goal of this study is to evaluate whether the effectiveness of cCXL is non-inferior to sCXL in terms of flattening of the cornea and halting keratoconus progression. Treating only the affected zone could be beneficial for minimalizing the risk of damaging surrounding tissues and faster wound healing. Recent non-randomized studies suggest that a customized crosslinking protocol based on the tomography of the patient's cornea may stop the progression of keratoconus and result in flattening of the cornea. TRIAL REGISTRATION: This study was prospectively registered at ClinicalTrials.gov on August 31st, 2020, the identifier of the study is NCT04532788.

Ocular surface immune cell diversity in dry eye disease.

Dry eye disease (DED) is a multifactorial chronic ocular surface inflammatory condition. Disease severity has been directly related to the immuno-inflammatory status of the ocular surface. Any perturbation in the orchestrated functional harmony between the ocular surface structural cells and immune cells, both resident and trafficking ones, can adversely affect ocular surface health. The diversity and contribution of ocular surface immune cells in DED have been of interest for over a couple of decades. As is true with any mucosal tissue, the ocular surface harbors a variety of immune cells of the innate-adaptive continuum and some of which are altered in DED. The current review curates and organizes the knowledge related to the ocular surface immune cell diversity in DED. Ten different major immune cell types and 21 immune cell subsets have been studied in the context of DED in human subjects and in animal models. The most pertinent observations are increased ocular surface proportions of neutrophils, dendritic cells, macrophages, and T cell subsets (CD4+; CD8+; Th17) along with a decrease in T regulatory cells. Some of these cells have demonstrated disease-causal association with ocular surface health parameters such as OSDI score, Schirmer's test-1, tear break-up time, and corneal staining. The review also summarizes various interventional strategies studied to modulate specific immune cell subsets and reduce DED severity. Further advancements would enable the use of ocular surface immune cell diversity, in patient stratification, i.e. DED-immunotypes, disease monitoring, and selective targeting to resolve the morbidity related to DED.

Type 1-type 2 interferon imbalance in dry eye disease.

Purpose: Dry eye disease (DED) is characterized by altered ocular surface proinflammatory and antiinflammatory factors. Interferons (IFNs) are a class of pleiotropic cytokines well known for their antimicrobial, inflammatory, and immunomodulatory roles. Hence, this study investigates the ocular surface expression of different types of IFNs in patients with DED. Methods: The cross-sectional, observational study included patients with DED and normal subjects. Conjunctival impression cytology (CIC) samples were obtained from the study subjects (controls, n = 7; DED, n = 8). The mRNA expression levels of type 1 IFN (IFNα, IFNß), type 2 IFN (IFNγ), and type 3 IFN (IFNλ1, IFNλ2, IFNλ3) were measured by quantitative PCR (polymerase chain reaction) in CIC samples. IFNα and IFNγ expression under hyperosmotic stress was also studied in human corneal epithelial cells (HCECs) in vitro. Results: The mRNA expression levels of IFNα and IFNß were significantly lower and that of IFNγ was significantly higher in DED patients compared to healthy controls. The mRNA levels of IFNα, IFNß, and IFNλ were significantly lower compared to IFNγ in DED patients. An inverse association between tonicity-responsive enhancer-binding protein (TonEBP; hyperosmotic stress maker) and IFNα or IFNß expression and a positive association between TonEBP and IFNγ expression was observed in CIC samples. The expression of IFNα was lower than IFNγ in HCECs undergoing hyperosmotic stress compared to HCECs without the stress. Conclusion: The presence of an imbalance between type 1 and type 2 IFNs in DED patients suggests newer pathogenic processes in DED, plausible ocular surface infection susceptibility in DED patients, and potential therapeutic targets in the management of DED.