Prevalence data for total corneal astigmatism in cataract patients.

PURPOSE: To report the prevalence data for total corneal astigmatism (TCA) in cataract patients. METHODS: The authors retrospectively collected and analyzed the preoperative biometric data of the patients who underwent cataract surgery in the Department of Ophthalmology, Peking University Third Hospital, from January 2019 to May 2023. RESULTS: The mean age of the 10817 patients was 71 ± 10 years; the male/female ratio was 4653/6164. The mean TCA obtained by the IOLMaster 700 (Carl Zeiss Meditec AG, Jena, Germany), the Abulafia-Koch (AK) formula, and the Barrett toric calculator was 1.11 ± 0.81 diopter (D), 1.13 ± 0.75 D, and 1.12 ± 0.74 D respectively, which was significantly greater than the mean standard keratometric (K) astigmatism (0.99 ± 0.75 D) obtained by IOLMaster 700. Against-the-rule (ATR) astigmatism was dominant in all the TCA measurements, and its proportion increased with age. TCA measurements by different methods exhibit high variability, with a total of 1574 (8.9%) data sets from 1016 (9.4%) patients showing a difference larger than 0.5 D in at least one pair of TCA measurements. CONCLUSION: The use of TCA rather than K astigmatism significantly influenced the choice of intraocular lenses (IOLs) as more patients would be candidates for toric IOLs. It was essential to carefully compare and select TCA obtained with multiple methods for optimal postoperative visual quality.

Profiles, Distribution, and Functions of Gamma Delta T Cells in Ocular Surface Homeostasis and Diseases.

The ocular surface microenvironment, containing the cornea, conjunctiva, and lacrimal gland, constitutes the mucosal frontline of the eye and houses a myriad of immune cells. As a part of unconventional T cells, gamma delta (γδ) T cells differ in the development and functions from canonical alpha beta (αß) T cells. They are predominantly situated in mucosal sites throughout the body, including ocular surface tissues. Recent research has elucidated that γδ T cells serve as the primary interleukin-17A (IL-17A) source in the conjunctiva. They play a pivotal role in preserving ocular surface homeostasis and exhibit both protective and pathogenic roles in ocular surface diseases. This review delves into the general profiles of γδ T cells, their distribution in ocular surface tissues, and consolidates current insights into their functions in different conditions including dry eye disease, infectious keratitis, corneal wound healing, anterior chamber-associated immune deviation, allergic conjunctival disease, and diabetic ocular surface disease. The aim is to provide a systemic perspective on γδ T cells in the ocular surface microenvironment and outline potential directions for future studies.

Protocol to examine immune subpopulations in murine conjunctiva and lacrimal gland using flow cytometry.

Here, we present a protocol for the examination of immune cells in the murine conjunctiva and lacrimal gland using flow cytometry. We describe steps for dissection, preparation of high-quality single-cell suspensions, utilization of comprehensive staining panels, and optimization of flow cytometry voltage. We then detail procedures for compensation adjustments and the implementation of effective gating strategies. For complete details on the use and execution of this protocol, please refer to Ma et al.1.

Transmembrane Protein CMTM6 Alleviates Ocular Inflammatory Response and Improves Corneal Epithelial Barrier Function in Experimental Dry Eye.

Purpose: To investigate the impact of transmembrane protein CMTM6 on the pathogenesis of dry eye disease (DED) and elucidate its potential mechanisms. Methods: CMTM6 expression was confirmed by database analysis, real-time polymerase chain reaction (RT-PCR), western blot, and immunohistochemistry. Tear secretion was measured using the phenol red thread test. Immune cell infiltration was assessed through flow cytometry. Barrier function was evaluated by fluorescein sodium staining, immunofluorescence staining of zonula occludens 1 (ZO-1), and electric cell-substrate impedance sensing (ECIS) assessment. For silencing CMTM6 expression, siRNA and shRNA were employed, along with lentiviral vector-mediated overexpression of CMTM6. Proinflammatory cytokine levels were analyzed by RT-PCR and cytometric bead array (CBA) analysis. Results: CMTM6 showed high expression in healthy human and mouse corneal and conjunctival epithelium but was notably reduced in DED. Notably, this downregulation was correlated with disease severity. Cmtm6-/- dry eye (DE) mice displayed reduced tear secretion, severe corneal epithelial defects, decreased conjunctival goblet cell density, and upregulated inflammatory response. Additionally, Cmtm6-/- DE mice and CMTM6 knockdown human corneal epithelial cell-transformed (HCE-T) cells showed more severe barrier disruption and reduced expression of ZO-1. Knockdown of CMTM6 in HCE-T cells increased inflammatory responses induced by hyperosmotic stress, which was significantly mitigated by CMTM6 overexpression. Moreover, the level of phospho-p65 in hyperosmolarity-stimulated HCE-T cells increased after silencing CMTM6. Nuclear factor kappa B (NF-κB) p65 inhibition (JSH-23) reversed the excessive inflammatory responses caused by hyperosmolarity in CMTM6 knockdown HCE-T cells. Conclusions: The reduction in CMTM6 expression on the ocular surface contributes to the pathogenesis of DED. The CMTM6-NF-κB p65 signaling pathway may serve as a promising therapeutic target for DED.

Efficacy of topical 0.05% cyclosporine A and 0.1% sodium hyaluronate in post-refractive surgery chronic dry eye patients with ocular pain.

BACKGROUND: The management of post-refractive surgery dry eye disease (DED) can be challenging in clinical practice, and patients usually show an incomplete response to traditional artificial tears, especially when it is complicated with ocular pain. Therefore, we aim to investigate the efficacy of combined topical 0.05% cyclosporine A and 0.1% sodium hyaluronate treatment in post-refractive surgery DED patients with ocular pain unresponsive to traditional artificial tears. METHODS: We enrolled 30 patients with post-refractive surgery DED with ocular pain who were unresponsive to traditional artificial tears. Topical 0.05% cyclosporine A and 0.1% sodium hyaluronate were used for 3 months. They were evaluated at baseline and 1 and 3 months for dry eye and ocular pain symptoms and objective parameters, including Numerical Rating Scale (NRS), Neuropathic Pain Symptom Inventory modified for the Eye (NPSI-Eye), tear break-up time (TBUT), Schirmer I test (SIt), corneal fluorescein staining (CFS), corneal sensitivity, and corneal nerve morphology. In addition, tear levels of inflammatory cytokines and neuropeptides were measured using the Luminex assay. RESULTS: After 3 months of treatment, patients showed a statistically significant improvement in the ocular surface disease index (OSDI), TBUT, SIt, CFS, and corneal sensitivity (all P < 0.01) using linear mixed models. As for ocular pain parameters, the NRS and NPSI-Eye scores were significantly reduced (both P < 0.05) and positively correlated with the OSDI and CFS scores. Additionally, tear IL-1ß, IL-6, and TNF-α levels were improved better than pre-treatment (P = 0.01, 0.03, 0.02, respectively). CONCLUSION: In patients with post-refractive surgery DED with ocular pain, combined topical 0.05% cyclosporine A and 0.1% sodium hyaluronate treatment improved tear film stability, dry eye discomfort, and ocular pain, effectively controlling ocular inflammation. TRIAL REGISTRATION: Registration number: NCT06043908.

Analysis of Clinical Characteristics and Neuropeptides in Patients with Dry Eye with and without Chronic Ocular Pain after FS-LASIK.

INTRODUCTION: Chronic ocular pain, particularly prevalent in patients with dry eye disease and post-femtosecond laser-assisted laser in situ keratomileusis (FS-LASIK) surgery, presents with unclear clinical characteristics and an undefined pathogenesis. In this study, we aimed to compare clinical characteristics and tear neuropeptide concentrations in patients with dry eye disease (DED) with and without chronic ocular pain following FS-LASIK, and investigate correlations between ocular pain, clinical characteristics, and tear neuropeptide levels. METHODS: Thirty-eight post-FS-LASIK patients with DED were assigned to two groups: those with chronic ocular pain and those without chronic ocular pain. Dry eye, ocular pain, and mental health-related parameters were evaluated using specific questionnaires and tests. The morphology of corneal nerves and dendritic cells (DCs) was evaluated by in vivo confocal microscopy. Function of corneal innervation was evaluated by corneal sensitivity. Concentrations of tear cytokines (interleukin [IL]-6, IL-23, IL-17A, and interferon-γ) and neuropeptides (α-melanocyte-stimulating hormone, neurotensin, ß-endorphin, oxytocin, and substance P [SP]) were measured using the Luminex assay. RESULTS: Most patients with chronic ocular pain experienced mild to moderate pain; the most common types included stimulated pain (provoked by wind and light), burning pain, and pressure sensation. More severe dry eye (P < 0.001), anxiety symptoms (P = 0.026), lower Schirmer I test values (P = 0.035), lower corneal nerve density (P = 0.043), and more activated DCs (P = 0.041) were observed in patients with ocular pain. Tear concentrations of SP and oxytocin were significantly higher in patients with ocular pain (P = 0.001, P = 0.021, respectively). Furthermore, significant correlations were observed among ocular pain severity, SP, and anxiety levels. CONCLUSIONS: Patients with DED after FS-LASIK who have chronic ocular pain show more severe ocular and psychological discomfort and higher tear levels of neuropeptides. Furthermore, ocular pain severity is correlated with tear SP levels. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT05600985.

Interpretable Detection of Diabetic Retinopathy, Retinal Vein Occlusion, Age-Related Macular Degeneration, and Other Fundus Conditions.

Diabetic retinopathy (DR), retinal vein occlusion (RVO), and age-related macular degeneration (AMD) pose significant global health challenges, often resulting in vision impairment and blindness. Automatic detection of these conditions is crucial, particularly in underserved rural areas with limited access to ophthalmic services. Despite remarkable advancements in artificial intelligence, especially convolutional neural networks (CNNs), their complexity can make interpretation difficult. In this study, we curated a dataset consisting of 15,089 color fundus photographs (CFPs) obtained from 8110 patients who underwent fundus fluorescein angiography (FFA) examination. The primary objective was to construct integrated models that merge CNNs with an attention mechanism. These models were designed for a hierarchical multilabel classification task, focusing on the detection of DR, RVO, AMD, and other fundus conditions. Furthermore, our approach extended to the detailed classification of DR, RVO, and AMD according to their respective subclasses. We employed a methodology that entails the translation of diagnostic information obtained from FFA results into CFPs. Our investigation focused on evaluating the models' ability to achieve precise diagnoses solely based on CFPs. Remarkably, our models showcased improvements across diverse fundus conditions, with the ConvNeXt-base + attention model standing out for its exceptional performance. The ConvNeXt-base + attention model achieved remarkable metrics, including an area under the receiver operating characteristic curve (AUC) of 0.943, a referable F1 score of 0.870, and a Cohen's kappa of 0.778 for DR detection. For RVO, it attained an AUC of 0.960, a referable F1 score of 0.854, and a Cohen's kappa of 0.819. Furthermore, in AMD detection, the model achieved an AUC of 0.959, an F1 score of 0.727, and a Cohen's kappa of 0.686. Impressively, the model demonstrated proficiency in subclassifying RVO and AMD, showcasing commendable sensitivity and specificity. Moreover, our models enhanced interpretability by visualizing attention weights on fundus images, aiding in the identification of disease findings. These outcomes underscore the substantial impact of our models in advancing the detection of DR, RVO, and AMD, offering the potential for improved patient outcomes and positively influencing the healthcare landscape.

Comparison of binocular visual quality in six treatment protocols for bilateral cataract surgery with presbyopia correction: a prospective two-center single-blinded cohort study.

OBJECTIVE: To compare the postoperative binocular visual quality in six treatment protocols for bilateral age-related cataract surgery with presbyopia correction for clinical decisions. MATERIALS AND METHODS: In this prospective two-center single-blinded cohort study, participants from North or South China who underwent bilateral phacoemulsification and intraocular lens implantation were divided into six protocols: monovision, diffractive bifocal, mixed, refractive bifocal, trifocal, and micro-monovision extended range of vision (EROV). Binocular visual quality was evaluated at 3 months postoperatively, including binocular uncorrected full-range visual acuity, binocular defocus curves (depth of focus [DoF] and area under the curve [AUC]), binocular visual function (fusion function and stereopsis), binocular subjective spectacle independence rates, visual analog scale (VAS) of overall satisfaction, 25-item visual function questionnaire (VFQ-25), and binocular dysphotopsia symptoms. RESULTS: Of the 300 enrolled patients, 272 (90.7%; 544 eyes) were analyzed. The trifocal protocol showed excellent binocular full-range visual acuity and the best performance for most DoFs and AUCs. The monovision protocol presented the worst binocular visual quality in most perspectives, especially in convergence, distance, and near stereopsis (p < 0.001). The full-range subjective spectacle independence rates were sorted from highest to lowest as follows: trifocal (84.8%), refractive bifocal (80.9%), EROV (80.0%), mixed (73.3%), diffractive bifocal (65.2%), and monovision (32.6%) protocols, with no statistically significant differences between the former five protocols (p > 0.05). The EROV protocol achieved the highest VAS and VFQ-25 scores. The incidence of postoperative binocular dysphotopsia symptoms was comparable in all protocols. CONCLUSIONS: The trifocal protocol showed the best performance, and the monovision protocol presented the worst performance in most perspectives of binocular visual quality for presbyopia correction. The refractive bifocal, mixed, or EROV protocols can provide an approximate performance as a trifocal protocol. Ophthalmologists can customize therapies using different protocols.

Clinical Characteristics and Tear Film Biomarkers in Patients With Chronic Dry Eye Disease After Femtosecond Laser-Assisted Laser in Situ Keratomileusis.

PURPOSE: To investigate clinical characteristics and tear film biomarkers of patients with chronic dry eye disease (DED) following femtosecond laser-assisted laser in situ keratomileusis (FS-LASIK). METHODS: Patients were divided into the chronic DED after FS-LASIK (n = 36), DED without FS-LASIK (n = 39), and normal control (without FS-LASIK; n = 34) groups. Dry eye, pain, and psychological-related symptoms were evaluated using the Ocular Surface Disease Index (OSDI), Numerical Rating Scale (NRS), Neuropathic Pain Symptom Inventory Modified for the Eye (NPSI-Eye), and Hamilton Anxiety Rating Scale (HAMA) questionnaires. Ocular surface parameters, tear cytokines, and neuropeptide concentrations were evaluated with specific tests. RESULTS: The DED after FS-LASIK group showed higher corneal fluorescein staining scores, but lower OSDI and NPSI-Eye scores than the DED without FS-LASIK group (all P < .05). Corneal sensitivity and nerve density decreased in the DED after FS-LASIK group (all P < .01). Granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin (IL)-17A, IL-23, alpha-melanocyte stimulating hormone (α-MSH), oxytocin, and substance P levels were highest in the DED after FS-LASIK group, followed by the DED without FS-LASIK and normal control groups (all P < .05). Interferon-γ and neurotensin levels were only significantly higher in the DED after FS-LASIK group (all P < .05). CONCLUSIONS: Patients with chronic DED after FS-LASIK showed milder ocular symptoms, greater epithelial damage, and higher levels of tear inflammatory cytokines and neuropeptides than patients with DED without FS-LASIK, indicating that the nervous and immune systems may play significant roles in FS-LASIK-related chronic DED development. [J Refract Surg. 2023;39(8):556-563.].

Comparison of mucin levels at the ocular surface of visual display terminal users with and without dry eye disease.

BACKGROUND: The long-term use of visual display terminals (VDT) is linked to an increased risk of dry eye disease (DED). Numerous studies have indicated that ocular mucins play a vital role in the pathogenesis of DED. Therefore, we aimed to evaluate (1) whether mRNA levels of membrane-associated mucins (MAMs), including MUC1, MUC4, MUC16, and MUC20, as well as MUC5AC are altered in conjunctival cells of VDT users with and without DED and (2) the relationship between mucin levels and subjective and objective tests of DED in VDT users. METHODS: Seventy-nine VDT users were enrolled and divided into DED (n = 53) and control (n = 26) groups. All participants were evaluated for parameters of DED using the Ocular Surface Disease Index (OSDI) questionnaire, tear breakup time (TBUT), corneal fluorescein staining (CFS), lissamine green (LG) staining, and tear meniscus height (TMH). Based on the conjunctival impression cytology (CIC) method, differences in MUC1, MUC4, MUC16, MUC20, and MUC5AC mRNA expression levels were observed between the DED and control groups, and between symptomatic and asymptomatic participants. RESULTS: The DED group showed significantly decreased MUC1, MUC16, and MUC20 expressions (all P < 0.05) compared to the control group. In addition, these mucin levels were lower in subjects with frequent ocular symptoms (foreign body sensation, blurred vision and painful or sore eyes) than in asymptomatic participants (all P < 0.05). Correlation analysis revealed that MUC1, MUC16, and MUC20 levels in VDT users were positively correlated with TBUT or TMH, or both. However, no significant relationship was found between MUC4 and MUC5AC levels and the DED parameters. CONCLUSION: VDT users with an increased frequency of ocular discomfort or a diagnosis of DED had a decreased MUC1, MUC16 and MUC20 mRNA expression in their conjunctival cells. MAMs deficiency in the conjunctival epithelium may be one of the mechanisms leading to tear film instability and DED in VDT users.

Mapping Resident Immune Cells in the Murine Ocular Surface and Lacrimal Gland by Flow Cytometry.

BACKGROUND: The ocular surface and lacrimal gland have a frontline position in mucosal immunology. However, there have been few updates to the immune cell atlas of these tissues in recent years. PURPOSE: To map the immune cells in murine ocular surface tissues and lacrimal gland. METHODS: Central and peripheral corneas, conjunctiva, and lacrimal gland were dissociated into single cell suspensions, followed by flow cytometry. Discrepancy of immune cells between the central and peripheral corneas was compared. In the conjunctiva and lacrimal gland, myeloid cells were clustered by tSNE and FlowSOM based on the expression of F4/80, Ly6C, Ly6G, and MHC II. ILCs, type 1 immune cells, and type 3 immune cells were analyzed. RESULTS: The number of immune cells in peripheral corneas was about 16 folds of that in central corneas. B cells accounted for 8.74% of immune cells in murine peripheral corneas. In the conjunctiva and lacrimal gland, most myeloid cells tended out to be monocytes, macrophages, and classical dendritic cells (cDCs). ILC3 were 6.28% and 3.63% of ILCs in the conjunctiva and lacrimal gland, respectively. Th1, Tc1, and NK cells were predominant type 1 immune cells. γδ T17 cells and ILC3 outnumbered Th17 cells among type 3 T cells. CONCLUSION: B cells resident in murine corneas were reported for the first time. Additionally, we proposed a strategy of clustering myeloid cells to better understand their heterogeneity in the conjunctiva and lacrimal gland based on tSNE and FlowSOM. Furthermore, we identified the ILC3 in the conjunctiva and lacrimal gland for the first time. Compositions of type 1 and type 3 immune cells were summarized. Our study provides a fundamental reference and novel insights for ocular surface immune homeostasis and diseases.

Elevated Neuropeptides in Dry Eye Disease and Their Clinical Correlations.

PURPOSE: The goal of this study was to assess neuropeptide levels in patients with dry eye disease (DED) and investigate their correlations with clinical characteristics. METHODS: This study included 38 eyes of 38 patients diagnosed with DED (DED group) and 38 eyes of 38 healthy volunteers without DED (control group). Ocular surface evaluation was performed. The severity of dry eye symptoms and signs in the DED group was graded. Neuropeptides [substance P (SP), alpha-melanocyte-stimulating hormone (α-MSH), ß-endorphin, neurotensin, and oxytocin] and inflammatory cytokines levels were measured in basal tears. The link between neuropeptides and clinical parameters was investigated using Spearman rank correlation. RESULTS: Overall, 76.3% of patients in the DED group showed dry eye symptoms and signs that were inconsistent in severity. Compared with the control group, the DED group showed higher levels of SP, α-MSH, and oxytocin in tears (P = 0.012, P = 0.030, and P = 0.006, respectively), but similar levels of ß-endorphin and neurotensin (P = 0.269 and P = 0.052). The levels of SP, α-MSH, and oxytocin were elevated in DED patients with higher grading of symptoms than clinical signs (all P < 0.05). SP, α-MSH, and oxytocin levels in tears were positively correlated with Ocular Surface Disease Index scores, frequency of sensitivity to light, and frequency of blurred vision (all P < 0.05). CONCLUSIONS: The increased tear levels of SP, α-MSH, and oxytocin may be linked to ocular discomfort in DED. Neuropeptides may play a key role in the development of DED, especially in DED patients with more severe symptoms than clinical signs.

Cost-Effectiveness of Presbyopia Correction Among Seven Strategies of Bilateral Cataract Surgery Based on a Prospective Single-Blind Two-Center Trial in China.

INTRODUCTION: The aim of this study was to explore a method to rank the cost-effectiveness of presbyopia correction in diverse strategies of bilateral cataract surgery to provide references for healthcare policymakers in rationalizing resource utilization and surgeons in customizing patient management. METHODS: The cost-effectiveness analysis based on a prospective single-blind two-center clinical trial included seven strategies in bilateral cataract surgery: monofocal, monovision, diffractive bifocal, blended, refractive bifocal, trifocal, and extended depth of focus (EDOF) strategies. The effectiveness according to the objective spectacle independence rate (hereafter "rate", a novel indicator defined as the proportion of patients with binocular uncorrected distance, intermediate and near visual acuity all better than 0.1 logMAR, logarithm of the minimum angle of resolution), costs, average cost-effectiveness ratios (ACERs, $/1% rate), and incremental cost-effectiveness ratios (ICERs, $/1% incremental rate) were estimated. RESULTS: In 194 participants (388 eyes), the trifocal strategy achieved the highest rate [93.10% (95% confidence interval (CI) 83.8-102.35%)]. The refractive bifocal strategy had the minimum ACER [$45.54/1% rate (95% CI 34.57-56.50)], followed by the blended [$59.10/1% rate (95% CI 31.72-86.48)], diffractive bifocal [$69.06/1% rate (95% CI 30.89-107.21)], EDOF [$72.85/1% rate (95% CI 52.02-93.70)], trifocal [$93.01/1% rate (95% CI 83.23-102.79)], monovision [$136.83/1% rate (95% CI - 55.40 to 329.14)], and monofocal [$264.45/1% rate (95% CI - 97.45 to 626.55)] strategies. Compared with the refractive bifocal strategy, the probabilities that the trifocal strategy (ICER $289.74/1% incremental rate) is very cost-effective and cost-effective were 81.7% and 93.2%, respectively, at the wiliness-to-pay threshold of one and three times China's annual disposable income per capita in 2021 per 10% incremental rates. CONCLUSIONS: Cost-effectiveness analysis with ACER and ICER according to objective spectacle independence rate is a helpful tool to identify highly cost-effective presbyopia-correcting strategies in cataract surgery for clinical and policy decisions. TRIAL REGISTRATION: Clinicaltrials.gov (NCT04265846).

Progress of Bulbar Conjunctival Microcirculation Alterations in the Diagnosis of Ocular Diseases.

Bulbar conjunctival microcirculation is a microvascular system distributed in the translucent bulbar conjunctiva near the corneal limbus. Multiple ocular diseases lead to bulbar conjunctival microcirculation alterations, which means that bulbar conjunctival microcirculation alterations would be potential screening and diagnostic indicators for these ocular diseases. In recent years, with the emergence and application of a variety of noninvasive observation devices for bulbar conjunctiva microcirculation and new image processing technologies, studies that explored the potential of bulbar conjunctival microcirculation alterations in the diagnosis of ocular diseases have been emerging. However, the potential of bulbar conjunctival microcirculation alterations as indicators for ocular diseases has not been exploited to full advantage. The observation devices, image processing methods, and algorithms are not unified. And large-scale research is needed to concrete bulbar conjunctival microcirculation alterations as indicators for ocular diseases. In this paper, we provide an update on the progress of bulbar conjunctival microcirculation alterations in the diagnosis of ocular diseases in recent five years (from January 2017 to March 2022). Relevant ocular diseases include contact lens wearing, dry eye, conjunctival malignant melanoma, conjunctival nevus, and diabetic retinopathy.

Evaluation of Ocular Surface Characteristics in Dry Eye Disease With and Without Soft Contact Lens Wear: A Comparative Study.

OBJECTIVES: To investigate ocular surface alterations and in vivo confocal microscopic characteristics of the cornea in dry eye disease (DED) with contact lens wear (CLW). METHODS: Sixty participants were divided into three groups: DED with CLW (n=20), DED without CLW (n=20), and normal control (n=20). Ocular surface parameters were evaluated. Basal tears and in vivo confocal microscopy images of the cornea were collected. Multiplex bead analysis was used to assess interleukin (IL)-6, IL-1ß, tumor necrosis factor (TNF)-α, nerve growth factor (NGF), and substance P (SP) in tears. Nerve morphology and dendritic cell density in corneal subbasal nerve images were calculated. RESULTS: The DED with CLW group showed significantly higher ocular surface staining scores ( P =0.022) and higher levels of IL-1ß, NGF, and SP in tears ( P =0.014, P =0.004 and P =0.025) than the DED without CLW group. Corneal dendritic cell density in the DED with CLW group was significantly higher than that in the normal controls ( P =0.001) and DED without CLW group ( P =0.043). Tear cytokine levels of IL-1ß, NGF, and SP were correlated with ocular surface parameters in the DED with CLW group. Moreover, the years of CLW were positively correlated with corneal dendritic cell density (r=0.527, P =0.017) and negatively correlated with corneal nerve density (r=-0.511, P =0.021). CONCLUSIONS: Patients with DED with CLW showed greater epithelial damage, elevated inflammatory cytokines and neuromediators in tears, and higher corneal dendritic cell density than patients with DED without CLW. The immune and nervous systems may be involved in contact lens-related DED.

Evaluations of wavefront aberrations and corneal surface regularity in dry eye patients measured with OPD Scan III.

AIM: To compare the wavefront aberrations and corneal surface regularity between dry eye (DE) patients and normal subjects and assess its diagnostic performance for DE measured with OPD Scan-III. METHODS: Fifty right eyes of 50 DE patients and 31 right eyes of normal subjects were included. The examinations for ocular surface including logarithm of the minimum angle of resolution best-corrected distance visual acuity (logMAR BCVA) the ocular surface disease index (OSDI), tear film break-up time (TBUT) and corneal fluorescein staining (CFS). OPD Scan-III was used to measure anterior corneal aberrations including total corneal aberrations, high order aberration (HOA), coma, trefoil, spherical aberration (SA), standard deviation of corneal power (SDP), surface regularity index (SRI) and surface asymmetry index (SAI). Statistical analysis were assessed with nonparametric tests and Spearman's correlations. All parameters were also analyzed for sensitivity, specificity, and receiver operating characteristics (ROC) curves. RESULTS: Wavefront aberrations parameters including total corneal aberrations, HOA, coma, trefoil, and SA in DE group were significantly higher than those in normal group (P<0.001). Corneal surface regularity parameters including SRI and SAI in DE group were significantly higher than both in normal group (P<0.05). All the wavefront aberrations parameters had significant correlations with ocular surface parameters (P<0.05). The logMAR BCVA had positive correlations with SAI and SRI (all P<0.001). CFS scores had positive correlations with SAI and SRI (all P<0.001). All the wavefront aberrations parameters showed good diagnosis sensitivity and specificity, however, the corneal regularity parameters showed only good specificity but poor sensitivity. The cut-off value selected for trefoil in diagnosis DE showed the highest area under the curve (AUC, 0.921) values as compared to the other parameters with sensitivity of 0.955 and specificity of 0.867. CONCLUSION: Wavefront aberrations and corneal surface regularity are increased in DE patients and also correlated with ocular surface parameters. Wavefront aberrations parameters have potential to be indicators to diagnosis and monitor DE.

Quantification of Increased Corneal Subbasal Nerve Tortuosity in Dry Eye Disease and Its Correlation With Clinical Parameters.

Purpose: This study quantified corneal subbasal nerve tortuosity in dry eye disease (DED) and investigated its correlation with clinical parameters by proposing an aggregated measure of tortuosity (Tagg). Methods: The sample consisted of 26 eyes of patients with DED and 23 eyes of healthy volunteers, which represented separately the dry eye group and the control group. Clinical evaluation of DED and in vivo confocal microscopy analysis of the central cornea were performed. Tagg incorporated six metrics of tortuosity. Corneal subbasal nerve images of subjects and a validation data set were analyzed using Tagg. Spearman's rank correlation was performed on Tagg and clinical parameters. Results: Tagg was validated using 1501 corneal nerve images. Tagg was higher in patients with DED than in healthy volunteers (P < 0.001). Tagg was positively correlated with the ocular surface disease index (r = 0.418, P = 0.003) and negatively correlated with tear breakup time (r = -0.398, P = 0.007). There was no correlation between Tagg and visual analog scale scores, corneal fluorescein staining scores, or the Schirmer I test. Conclusions: Tagg was validated for quantification of corneal subbasal nerve tortuosity and was higher in patients with DED than in healthy volunteers. A higher Tagg may be linked to ocular discomfort, visual function disturbance, and tear film instability. Translational Relevance: Corneal subbasal nerve tortuosity is a potential biomarker for corneal neurobiology in DED.

Pigment epithelium-derived factor (PEDF) plays anti-inflammatory roles in the pathogenesis of dry eye disease.

PURPOSE: To investigate the expression of pigment epithelium-derived factor (PEDF) in ocular surface in dry eye disease (DED) and its anti-inflammatory roles and mechanisms, clinically and by experiments in vivo and in vitro. METHODS: A cross-sectional study was conducted to detect the expression of PEDF in tears of dry eye patients by enzyme-linked immunosorbent assay (ELISA). Using dry eye mouse model and human corneal epithelial cells (hCECs) stimulated by hyperosmolarity or inflammatory cytokines, expression of PEDF in corneal epithelial cells, stroma and conjunctiva was quantified by real-time polymerase chain reaction, ELISA and Western blot. Next, either dry eye mice or hyperosmotic hCECs were treated with recombinant PEDF or neutralizing antibodies, and the expressions of inflammatory cytokines and immune cells were detected. Finally, Western blot was performed on MAPK and NF-κB to investigate the signaling pathways by which PEDF played its roles. RESULTS: Concentrations of PEDF were increased in tears of dry eye patients. Increased PEDF was observed in corneal epithelial cells (CECs) rather than corneal stroma or conjunctiva in dry eye mice. Furthermore, hCECs exposed to hyperosmolarity showed upregulation of PEDF. In vivo and in vitro studies showed that PEDF suppressed the expression of inflammatory cytokines including IL-1ß, IL-6, TNF-α and IL-17A, as well as the percentage of Th17 cells in DED. Further investigation showed that PEDF inhibited the phosphorylation of MAPK p38 and JNK in hyperosmotic hCECs. CONCLUSIONS: CECs derived PEDF is increased in DED. PEDF plays anti-inflammatory and immunoregulatory roles in the pathogenesis of DED.

Optical quality in patients with dry eye before and after treatment.

CLINICAL RELEVANCE: Dry eye disease could result in vision-related subjective symptoms even in patients with good best-corrected visual acuity. The standard deviation of corneal power and the surface asymmetry index could be indicators of treatment efficacy in dry eye. BACKGROUND: Few studies have examined changes in optical quality before and after dry eye treatment. Here, we evaluated changes in optical quality in patients with dry eye before and after treatment and identified potential indicators of dry eye-treatment efficacy. METHODS: Twenty-five right eyes of 25 untreated patients with dry eye were included. The same ocular-surface and optical-quality examinations were performed before and after two-weeks of treatment with hyaluronate in conjunction with fluorometholone eye drops. The Ocular Surface Disease Index, tear film break-up time, and corneal fluorescein staining were measured. Contrast sensitivity was used to measure resolution capability, the double-pass Optical Quality Analysis System to examine the modulation transfer function, Strehl ratio, and objective scattering index, and OPD Scan III to measure anterior corneal aberrations over 4-mm analytical zones including total corneal and high-order aberrations. The standard deviation of corneal power, surface regularity index, and surface asymmetry index were also measured. Paired sample t-tests and Spearman's correlations were used for the analyses. RESULTS: The Ocular Surface Disease Index, tear film break-up time, and corneal fluorescein staining improved after two weeks of treatment. Contrast sensitivity in photopic, photopic with glare, scotopic, and scotopic with glare conditions all improved (p < 0.05), as did the modulation transfer function, Strehl ratio, and objective scattering index (p = 0.001, p = 0.008, and p = 0.001, respectively). Total corneal aberrations and the surface regularity index did not significantly differ before and after treatment; corneal high-order aberrations, standard deviation of corneal power, and the surface asymmetry index significantly improved after treatment (p = 0.045, p = 0.019, and p = 0.049, respectively). Changes in standard deviation of corneal power and in surface asymmetry index correlated with change in corneal fluorescein staining (p = 0.006 and p = 0.007, respectively). CONCLUSION: Optical quality in patients with dry eye improved after treatment. The standard deviation of corneal power and surface asymmetry index could be indicators of treatment efficacy in dry eye.