Electroencephalogram-detected stress levels in the frontal lobe region of patients with dry eye.

PURPOSE: To evaluate stress levels extracted from prefrontal electroencephalogram (EEG) signals and investigate their relationship with dry eye symptoms. METHODS: This prospective, cross-sectional, comparative study included 25 eyes of 25 patients with aqueous tear-deficient dry eye (low Schirmer group), 25 eyes of 25 patients with short tear breakup time dry eye (short breakup time group), and 24 eyes of 24 individuals without dry eye. An EEG test, the Japanese version of the Ocular Surface Disease Index (OSDI), and a stress questionnaire were administered. EEG-detected stress levels were assessed under three conditions: eyes closed, eyes open, and eyes open under ocular surface anesthesia. RESULTS: Stress levels were significantly lower when the eyes were closed than when they were open in all groups (all P < 0.05). Stress levels during eyes open under ocular surface anesthesia were significantly lower than those during eyes open without anesthesia only in the low Schirmer group; no differences were found between the short breakup time and control groups. OSDI scores were associated with EEG-detected stress levels (P = 0.06) and vital staining score (P < 0.05) in the low Schirmer group; they were not associated with EEG-detected stress (P > 0.05), but with subjective stress questionnaire scores and breakup time values in the short breakup time group (P < 0.05). CONCLUSIONS: In the low Schirmer group, peripheral nerve stimulation caused by ocular surface damage induced stress reactions in the frontal lobe, resulting in dry eye symptoms. Conversely, in the short breakup time group, the stress response in the frontal lobe was not related to symptom development.

Models for Meibomian gland dysfunction: In vivo and in vitro.

Meibomian gland dysfunction (MGD) is a chronic abnormality of the Meibomian glands (MGs) that is recognized as the leading cause of evaporative dry eye worldwide. Despite its prevalence, however, the pathophysiology of MGD remains elusive, and effective disease management continues to be a challenge. In the past 50 years, different models have been developed to illustrate the pathophysiological nature of MGD and the underlying disease mechanisms. An understanding of these models is crucial if researchers are to select an appropriate model to address specific questions related to MGD and to develop new treatments. Here, we summarize the various models of MGD, discuss their applications and limitations, and provide perspectives for future studies in the field.

Efficacy and safety of trigeminal parasympathetic pathway stimulation for dry eye: A systematic review and meta-analysis.

This study aimed to investigate the efficacy and safety of trigeminal parasympathetic pathway (TPP) stimulation in the treatment of dry eye. A comprehensive search for randomized clinical trials was performed in seven databases (MEDLINE, Embase, CENTRAL, etc.) up to 28 February 2023. After screening the suitable studies, the data were extracted and transformed as necessary. Data synthesis and analysis were performed using Review Manager 5.4, and the risk of bias and quality of evidence were evaluated with the recommended tools. Fourteen studies enrolling 1714 patients with two methods (electrical and chemical) of TPP stimulation were included. Overall findings indicate that TPP stimulation was effective in reducing subjective symptom score (standardized mean difference [SMD], -0.45; 95% confidence interval [CI], -0.63 to -0.28), corneal fluorescence staining (mean difference [MD], -0.78; 95% CI, -1.39 to -0.18), goblet cell area (MD, -32.10; 95% CI, -54.58 to -9.62) and perimeter (MD, -5.90; 95% CI, -10.27 to -1.53), and increasing Schirmer's test score (SMD, 0.98; 95% CI, 0.65 to 1.31) and tear film break-up time (SMD, 0.57; 95% CI, 0.19 to 0.95). Compared to inactive or low-activity stimulation controls, it has a higher incidence of adverse events. Therefore, TPP stimulation may be an effective treatment for dry eye, whether electrical or chemical. Adverse events are relatively mild and tolerable. Due to the high heterogeneity and low level of evidence, the current conclusions require to be further verified.

Refitting contact lens dropouts into a modern daily disposable contact lens.

PURPOSE: To determine the number of previous contact lens (CL) wearers who could be comfortably refitted into delefilcon A (DAILIES TOTAL1®) CLs. METHODS: This was a 6-month, three-visit study that recruited subjects who discontinued CLs within the past 2 years because of discomfort or dryness symptoms. Subjects were required to have Standard Patient Evaluation of Eye Dryness (SPEED) questionnaire scores ≤3 and to be able to wear spherical study CLs. Subjects were asked to complete a ±50 comfort visual analogue scale (VAS) at 1 month and a Likert questionnaire after 1 and 6 months of CL wear to understand the subjects' CL experience. RESULTS: All 60 subjects who were fitted with the study CLs were still wearing them after 1 month, while one subject had dropped out by 6 months. Subjects had a median (interquartile range) age of 24.0 (7.0) years (71.7% female). They reported a median VAS score of 44.0 (8.0) units at the 1-month visit, with all reporting a comfortable score. At the 1-month/6-month visits, 98.3%/93.2%, 86.5%/78.0% and 93.2%/91.5% of subjects responded that they were very satisfied or satisfied with their vision, their end-of-day CL comfort and overall CL comfort, respectively. The same subjects responded that they were very likely or likely to continue to wear the study CLs at 1 (89.6%) and 6 months (80.7%) and to recommend the study CLs to a friend at 1 (98.3%) and 6 months (93.2%). CONCLUSIONS: The results suggest that when encountering a CL dropout, a practitioner could educate a patient about trying an alternative CL and consider delefilcon A lenses as an option.

End-of-day assessment of asymptomatic versus highly symptomatic soft contact lens wearers.

PURPOSE: To investigate differences in key clinical parameters between asymptomatic and highly symptomatic soft contact lens (CL) wearers after 14 h of wear. METHODS: In this pilot investigation, Phase 1 identified asymptomatic (CLDEQ-8 score ≤ 7) and highly symptomatic (CLDEQ-8 score ≥ 20) subjects after fitting with nelfilcon A CLs. Phase 2 investigated the following over a single nelfilcon A CL-wearing day (14 ± 2 h): blinking characteristics, tear meniscus height (TMH), non-invasive tear break-up time (NIBUT), tear film osmolarity and eyelid margin staining. Parameters for the two groups were compared using linear mixed models and post-hoc testing. The relationship between comfort scores and the clinical parameters was also investigated. RESULTS: Overall, 161 and 42 subjects were enrolled into Phase 1 and 2, respectively. Twenty-five asymptomatic and 17 symptomatic subjects completed Phase 2. Lower eyelid TMH was decreased after 14 h in symptomatic compared with asymptomatic subjects (least square mean [LSM] difference -0.04 mm, 95% CI: -0.07, -0.01). Osmolarity was lower in symptomatic than in asymptomatic subjects at fitting (LSM difference -9.89, 95% CI: -18.91, -0.86). Upper eyelid margin staining was greater after 14 h in symptomatic than in asymptomatic subjects (LSM difference 0.53, 95% CI: 0.01, 1.05) and greater after 14 h than baseline in the symptomatic group (LSM difference 0.61, 95% CI: 0.16, 1.07). There was a significant relationship between comfort and upper eyelid margin staining (r = -0.40, 95% CI: -0.63, -0.11) and blink rate (r = -0.31, 95% CI: -0.57, -0.003). CONCLUSION: The potential parameters most effective in differentiating asymptomatic from symptomatic wearers were upper eyelid margin staining and lower TMH. The parameter with the strongest relationship to comfort was upper eyelid margin staining, where higher comfort scores were associated with lower levels of staining.

Rethinking Sjögren Beyond Inflammation: Considering the Role of Nerves in Driving Disease Manifestations.

ABSTRACT: Sjögren syndrome (SS) is a chronic inflammatory autoimmune disease characterized by destruction of mucosal glands resulting in dry eye and dry mouth. Ocular presentations can be heterogenous in SS with corneal nerves abnormalities that are structural, functional, or both. Some individuals present with corneal hyposensitivity, with a phenotype of decreased tear production and epithelial disruption. Others present with corneal hypersensitivity, with a phenotype of neuropathic pain including light sensitivity and pain out of proportion to signs of tear dysfunction. A similar correlate can be found outside the eye, with dry mouth predominating in some individuals while pain conditions predominate in others. Understanding how nerve status affects SS phenotype is an important first step to improving disease management by targeting nerve abnormalities, as well as inflammation.

Lens and solution properties in patients with and without midday fogging.

INTRODUCTION: Midday fogging is a complication of scleral lens (SL) wear that interrupts clear vision during the course of wear. SLs can be made with a variety of gas permeable materials, sizes and surface treatments, and various solutions are available for storing the lenses and for filling them before application on the eye. Many of these factors have been implicated as possible contributors to midday fogging. This study explored the lens and solution properties in habitual SL wearers with and without midday fogging. METHODS: In this prospective study, 48 habitual SL wearers were evaluated and asked to report whether they experienced midday fogging and if they removed their lenses during the day. They completed the Ocular Surface Disease Index (OSDI), which is a validated tool for dry eye assessment. Lens parameters (material, coatings and diameter) and lens storage and filling solutions were documented. Backward elimination of regression terms evaluated the lens and solution properties in those with and without fogging. OSDI scores were compared using the Mann-Whitney analysis. RESULTS: Collectively, the lens properties and solutions accounted for 27.7% of the variance related to midday fogging. None of the factors alone had a significant impact upon midday fogging. The median (interquartile range) OSDI score for those with fogging [37 (35)] was significantly different from those without fogging [10 (15)], with the scores corresponding to severe dry eye and normal eyes, respectively. CONCLUSION: SL wearers with midday fogging exhibited similar symptoms to patients with severe dry eye. Lens and solution characteristics may play a small role in patients with midday fogging, although changing just a single factor is not likely to impact its presence.

The Yin and Yang of non-immune and immune responses in meibomian gland dysfunction.

Meibomian gland dysfunction (MGD) is a leading cause of dry eye disease and one of the most common ophthalmic conditions encountered in eye clinics worldwide. These holocrine glands are situated in the eyelid, where they produce specialized lipids, or meibum, needed to lubricate the eye surface and slow tear film evaporation - functions which are critical to preserving high-resolution vision. MGD results in tear instability, rapid tear evaporation, changes in local microflora, and dry eye disease, amongst other pathological entities. While studies identifying the mechanisms of MGD have generally focused on gland obstruction, we now know that age is a major risk factor for MGD that is associated with abnormal cell differentiation and renewal. It is also now appreciated that immune-inflammatory disorders, such as certain autoimmune diseases and atopy, may trigger MGD, as demonstrated through a T cell-driven neutrophil response. Here, we independently discuss the underlying roles of gland and immune related factors in MGD, as well as the integration of these two distinct mechanisms into a unified perspective that may aid future studies. From this unique standpoint, we propose a revised model in which glandular dysfunction and immunopathogenic pathways are not primary versus secondary contributors in MGD, but are fluid, interactive, and dynamic, which we likened to the Yin and Yang of MGD.

Influential Signs of Dry Eye-Related Ocular Symptoms in Participants With Unstable Tear Film.

PURPOSE: The aim of this study was to investigate the factors influencing dry eye disease (DED)-related ocular symptoms in participants with short fluorescein tear break-up time (FTBUT). METHODS: This cross-sectional study included 82 participants with short FTBUT (<10 seconds). Examinations included Ocular Surface Disease Index (OSDI), FTBUT, average noninvasive tear break-up time (NIBUTave), lid wiper epitheliopathy, lipid layer thickness, blink rate, partial blink, tear meniscus height, and meibomian gland (MG) evaluation which included ratio of residual MG area (RMGA) and MG grade in tarsal plates. One-way analysis of variance was used to detect differences between symptomatic tear film instability group (FTBUT <5 s, OSDI ≥13), asymptomatic tear film instability group (FTBUT <5 s, OSDI <13), and control group (FTBUT ≥5 s, OSDI <13). A bivariate correlation, partial correlation, and multiple linear regression analyses were used to identify major factors. Only the right eye was included. RESULTS: Among the participants with FTBUT <5 seconds, symptomatic group showed less upper RMGA ( P < 0.001) and NIBUTave ( P = 0.010). OSDI was negatively associated with upper RMGA ( r = -0.450, P < 0.001) and NIBUTave ( r = -0.414, P = 0.001), and positively associated with upper MG grade ( r = 0.277, P = 0.027). Linear regression analysis showed that the upper RMGA significantly affected OSDI (B = -41.895, P = 0.001), while not significantly correlated with age, upper MG grade, and NIBUTave. CONCLUSIONS: The upper RMGA might be the main factor affecting DED-related discomfort in participants with unstable tear film, indicating an early ocular change in DED.

Review of clinical outcomes of a cationic emulsion tear substitute in patients with dry eye disease.

First-line options for the treatment of dry eye disease (DED) rely on artificial tears (ATs), among which cationic emulsion (CE)-based ATs have been developed in order to mimic the healthy tear film for an improved restoration of the ocular surface homeostasis. In this review, we describe the outcomes reported in several studies, assessing the mode of action, ocular tolerance and clinical performance of a CE-based AT. Pilot studies have revealed that CE-based ATs can increase the volume and stability of the tear film while limiting its evaporation rate. Larger studies have demonstrated that CE-based ATs play a significant role in the improvement of both objective and subjective DED parameters, including superior efficacy on DED symptoms compared to several other available AT formulation types. Concomitantly, CE-based ATs have been shown to help patients to prevent or recover from corneal defects associated with refractive surgery. These positive outcomes on ocular surface epithelia are likely due to the combination of unique rheological behaviour and intrinsic anti-inflammatory properties. Based on all clinical findings, CE-based ATs represent a valuable treatment option for patients with various etiologies of DED including evaporative forms and would deserve evaluation of benefits in other surgical intervention types triggering DED.

Is the Sex Difference a Clue to the Pathomechanism of Dry Eye Disease? Watch out for the NGF-TrkA-Piezo2 Signaling Axis and the Piezo2 Channelopathy.

Dry eye disease (DED) is a multifactorial disorder with recognized pathology, but not entirely known pathomechanism. It is suggested to represent a continuum with neuropathic corneal pain with the paradox that DED is a pain-free disease in most cases, although it is regarded as a pain condition. The current paper puts into perspective that one gateway from physiology to pathophysiology could be a Piezo2 channelopathy, opening the pathway to a potentially quad-phasic non-contact injury mechanism on a multifactorial basis and with a heterogeneous clinical picture. The primary non-contact injury phase could be the pain-free microinjury of the Piezo2 ion channel at the corneal somatosensory nerve terminal. The secondary non-contact injury phase involves harsher corneal tissue damage with C-fiber contribution due to the lost or inadequate intimate cross-talk between somatosensory Piezo2 and peripheral Piezo1. The third injury phase of this non-contact injury is the neuronal sensitization process with underlying repeated re-injury of the Piezo2, leading to the proposed chronic channelopathy. Notably, sensitization may evolve in certain cases in the absence of the second injury phase. Finally, the quadric injury phase is the lingering low-grade neuroinflammation associated with aging, called inflammaging. This quadric phase could clinically initiate or augment DED, explaining why increasing age is a risk factor. We highlight the potential role of the NGF-TrkA axis as a signaling mechanism that could further promote the microinjury of the corneal Piezo2 in a stress-derived hyperexcited state. The NGF-TrkA-Piezo2 axis might explain why female sex represents a risk factor for DED.

Different perception of dry eye symptoms between patients with and without primary Sjogren's syndrome.

Here, we investigated the different perception of dry eye symptoms between in patients with and without primary Sjogren's syndrome (pSS). In this study, 221 patients with dry eye disease (DED) without pSS (non-SS DED group) and 55 patients with DED with pSS (SS DED group) were included. The ocular discomfort was evaluated using ocular surface disease index (OSDI) questionnaire and patients were further divided into 3 severity subgroups according to OSDI scores. The OSDI score was higher in the non-SS DED group even after matching corneal erosion scores despite the ocular surface erosions and tear deficiency was worse in the SS DED group. The corneal sensitivity was nearly normal in both groups without inter-group difference (Non-SS DED group: 5.82 ± 0.54 cm, SS DED group: 5.90 ± 0.29 cm, p = 0.217). Moreover, all clinical parameters were not significantly correlated with OSDI scores in both non-SS DED group and SS DED group. In the mild and severe OSDI subgroups, the ocular surface erosions and tear deficiency were worse in the SS DED group whereas the OSDI scores were not different between groups. In conclusion, clinicians should be aware that pSS patients may complain less of their discomfort unlike their actual severe status of DED.

Investigation of changes in the activity and function of dry eye-associated brain regions using the amplitude of low-frequency fluctuations method.

OBJECTIVE: The local characteristics of spontaneous brain activity in patients with dry eye (DE) and its relationship with clinical characteristics were evaluated using the amplitude of low-frequency fluctuations (ALFF) method. METHODS: A total of 27 patients with DE (10 males and 17 females) and 28 healthy controls (HCs) (10 males and 18 females) were recruited, matched according to sex, age, weight and height, classified into the DE and HC groups, and examined using functional magnetic resonance imaging (fMRI) scans. Spontaneous brain activity changes were recorded using ALFF technology. Data were recorded and plotted on the receiver operating characteristic (ROC) curve, reflecting changes in activity in different brain areas. Finally, Pearson correlation analysis was used to calculate the potential relationship between spontaneous brain activity abnormalities in multiple brain regions and clinical features in patients with DE. GraphPad Prism 8 (GraphPad Software, Inc.) was used to analyze the linear correlation between the Hospital Anxiety and Depression Scale and ALFF value. RESULTS: Compared with HCs, the ALFF values of patients with DE were decreased in the right middle frontal gyrus (MFG)/right inferior orbitofrontal cortex (OFC), left triangle inferior frontal gyrus, left MFG, and right superior frontal gyrus. In contrast, the ALFF value of patients with DE was increased in the left calcarine. CONCLUSION: There are significant fluctuations in the ALFF value of specific brain regions in patients with DE versus HCs. This corroborates previous evidence showing that the symptoms of ocular surface damage in patients with DE are related to dysfunction in specific brain areas.

Pathogenic Mechanism of Dry Eye-Induced Chronic Ocular Pain and a Mechanism-Based Therapeutic Approach.

Purpose: Dry eye-induced chronic ocular pain is also called ocular neuropathic pain. However, details of the pathogenic mechanism remain unknown. The purpose of this study was to elucidate the pathogenic mechanism of dry eye-induced chronic pain in the anterior eye area and develop a pathophysiology-based therapeutic strategy. Methods: We used a rat dry eye model with lacrimal gland excision (LGE) to elucidate the pathogenic mechanism of ocular neuropathic pain. Corneal epithelial damage, hypersensitivity, and hyperalgesia were evaluated on the LGE side and compared with the sham surgery side. We analyzed neuronal activity, microglial and astrocytic activity, α2δ-1 subunit expression, and inhibitory interneurons in the trigeminal nucleus. We also evaluated the therapeutic effects of ophthalmic treatment and chronic pregabalin administration on dry eye-induced ocular neuropathic pain. Results: Dry eye caused hypersensitivity and hyperalgesia on the LGE side. In the trigeminal nucleus of the LGE side, neuronal hyperactivation, transient activation of microglia, persistent activation of astrocytes, α2δ-1 subunit upregulation, and reduced numbers of inhibitory interneurons were observed. Ophthalmic treatment alone did not improve hyperalgesia. In contrast, continuous treatment with pregabalin effectively ameliorated hypersensitivity and hyperalgesia and normalized neural activity, α2δ-1 subunit upregulation, and astrocyte activation. Conclusions: These results suggest that dry eye-induced hypersensitivity and hyperalgesia are caused by central sensitization in the trigeminal nucleus with upregulation of the α2δ-1 subunit. Here, we showed that pregabalin is effective for treating dry eye-induced ocular neuropathic pain even after chronic pain has been established.

Hypochlorous Acid Can Be the Novel Option for the Meibomian Gland Dysfunction Dry Eye through Ultrasonic Atomization.

BACKGROUND: Dry eye is a multifactor disease which needs comprehensive treatments to keep the homeostasis of ocular surface. OBJECTIVE: To explore the effect of hypochlorous acid on the meibomian gland dysfunction dry eye through ultrasonic atomization. METHODS: We set this study of 0.01% HOCL and 0.1% hyaluronate by ultrasonic atomization. All the data was recorded at the 1st, 15th, 30th, and 55th days. The patients' complains, the meibum analysis, conjunctive congestion, corneal staining, Schirmer's I test, and NIBUT were recorded by K5M, the MMP-9, and IL-2 of tear by inflammation kit; the Demodex was recorded by microscopy. RESULTS: 53 patients have joined this study. There is no statistic difference between them on OSDI (day 15: p = 0.061, 30: p = 0.055, 55: p = 0.052); results show the 10.57 ± 0.13 and 12.54 ± 0.17 reduction on OSDI; the differences of both treatments are significant (∗∗ p < 0.01). Increased Schirmer's and TBUT are 3.27 ± 0.10 and 6.29 ± 0.10 (∗∗ p < 0.01) or 7.32 ± 1.72 s and 9.22 ± 1.41 s (∗ p < 0.05); the decreased conjunctive and corneal staining are 0.23 ± 0.07 and 0.45 ± 0.06 (∗∗ p < 0.01) or 0.42 ± 0.03 and 0.37 ± 0.02 (∗ p < 0.05) at both groups. The differences of MMP-9 and IL-2 negative rate are significant (Z = 0.896, ∗∗ p = 0.002 < 0.01; Z = 0.659, ∗∗ p = 0.001 < 0.01); the number of Demodex mites at first is 10 or 11, while the last is 2 or 6 (Z = -4.642, ∗∗ p < 0.01; Z = 2.742, p > 0.05). The Demodex count between them is significant (Z = -2.310, ∗ p = 0.032 < 0.05). The survival times (ST) of each stage at the HOCL are 110.75 (108.50 ± 24.50), 95.50 (90.25 ± 14.50), and 75.25 (73.48 ± 8.50) min which are shorter than those of control which are 155.50 (160.10 ± 21.50), 130.25 (128.25 ± 16.50), and 105.75 (102.50 ± 14.50) min (∗∗ p < 0.01). The Demodex eradication rate of HOCL is statistic significant (∗ p15th vs. 1stday = 0.028 < 0.05; ∗∗ p30th vs. 1stday = 0.002 < 0.01; ∗∗ p55th vs. 1stday = 0.0018 < 0.01). CONCLUSIONS: 0.01% HOCL improves the Demodex eradication by shortening the survival time; the HOCL acts on the ocular surface by reducing the inflammation. The ultrasonic atomization helps for the drug usage.

TearCare for the Treatment of Meibomian Gland Dysfunction in Adult Patients With Dry Eye Disease: A Masked Randomized Controlled Trial.

PURPOSE: The aim of this study was to demonstrate the safety and effectiveness of a single TearCare procedure compared with a single LipiFlow procedure in treatment of the dry eye disease associated with meibomian gland dysfunction. METHODS: In a multicenter, masked, randomized controlled trial, 135 subjects received a single TearCare (TC) treatment (n = 67) or a single LipiFlow (LF) treatment (n = 68) at baseline and were followed up for 1 month posttreatment. Tear film breakup time, meibomian gland function, and corneal and conjunctival staining scores were assessed as dry eye signs at baseline, 2 weeks, and 1 month; dry eye symptoms were assessed using the Ocular Surface Disease Index, Symptom Assessment in Dry Eye, and eye dryness questionnaires at baseline and 1 month. RESULTS: At 1 month posttreatment, both groups demonstrated significant improvements (P < 0.0001) in mean tear film breakup time and meibomian gland secretion score to 3.0 ± 4.4 and 11.2 ± 11.1 in the TC group and 2.6 ± 3.3 and 11.0 ± 10.4 in the LF group, respectively. The mean eye dryness, Symptom Assessment in Dry Eye, and Ocular Surface Disease Index scores were significantly reduced (P < 0.0001) by 35.4 ± 34.1, 38.2 ± 31.0, and 27.9 ± 20.5 in the TC group and 34.9 ± 26.9, 38.0 ± 25.9, and 23.4 ± 17.7 in the LF group, respectively. There were no statistically significant differences for any result between the groups. However, the TC group demonstrated numerically greater improvements consistently in all signs and symptoms. Device-related ocular adverse events were reported in 3 patients in the TC group (superficial punctate keratitis, chalazion, and blepharitis) and 4 patients in the LF group (blepharitis, 2 cases of foreign body sensation, and severe eye dryness). CONCLUSIONS: A single TearCare treatment significantly alleviates the signs and symptoms of dry eye disease in patients with meibomian gland dysfunction and is equivalent in its safety and effectiveness profile to LipiFlow treatment as shown in this 1-month follow-up study.

Impact of Graves Disease on Ocular Surface and Corneal Epithelial Thickness in Patients With and Without Graves Orbitopathy.

PURPOSE: Our aim was to assess ocular surface and tear film stability and corneal epithelial thickness (CET) in patients with Graves disease (GD) with and without Graves orbitopathy (GO). METHODS: This study included healthy age-matched controls and patients with GD. Symptoms (Ocular Surface Disease Index questionnaire) and signs (schirmer test and tear breakup time test) of dry eye disease were determined, according to the International Dry Eye Workshop II criteria of DED. CET map was also assessed. RESULTS: Twenty-four eyes were included in the control group, with a mean age of 41.00 ± 13.65 years, and 34 in the GD group, 18 with GO and 16 without GO, with a mean age of 44.44 ± 13.95 and 45.75 ± 10.59 years, respectively. All patients with GO had inactive disease (mean clinical activity score: 1.33 ± 0.69). Patients with GD had higher proportion of clinical diagnosis of dry eye disease (GO vs. GD without GO vs. controls: 77.77% vs. 75.00% vs. 4.17%), with higher Ocular Surface Disease Index (GO vs. GD without GO vs. controls: 15.44 vs. 15.06 vs. 9.88) and lower tear breakup time test (GO vs. GD without GO vs. controls: 6.33 s vs. 7.25 s vs. 11.63 s). Superior CET was lower in patients with GD (P < 0.05). No differences were found between patients with and without GO (P > 0.05). CONCLUSIONS: GD negatively influenced ocular surface and CET, with a higher level of eye dryness and corneal thinning regardless of GO status, suggesting that subclinical chronic inflammation may play a role in the pathogenesis of tear film and ocular surface stability.

Differential effect of maximal incremental treadmill exercise on tear secretion and tear film stability in athletes and non-athletes.

The study investigated the differential response to a single bout of maximal incremental treadmill exercise between athletes and non-athletes without dry eyes regarding tear secretion, tear film stability, visual acuity (VA), and stereoacuity. Additionally, the study examined the effect of gender and the duration of exercise on exercise-induced changes. Study participants included young university students aged 18-25 years who were athletes (male/female: 13/13) or non-athletes (male/female: 17/9). Participants underwent an aerobic exercise session using a treadmill and following the laid down Bruce treadmill test protocol till exhaustion. Measurements were taken in the order of distance VA, stereopsis, non-invasive tear break-up time (TBUT), and phenol red thread test, at baseline and after the exercise regimen. Within- and between-subject analyses using multiple t-tests with correction for multiple comparisons were performed to determine differences before and after exercise in athletes and non-athletes. Subsequently, ANCOVA was used to assess the influence of gender and the duration of exercise. The mean age (SD) of the athletes and the non-athletes was 22.4 ± 2.1 years and 21.8 ± 2.1 years, respectively (p = 0.357). Before exercise, the athletes had higher TBUT than non-athletes (14.6 ± 2.9 s vs. 11.9 ± 3.8 s; p = 0.021), but no difference was observed in any other ocular measurements. After exercise, the athletes showed significant improvement in tear secretion with the basal tear secretion increasing from 22.3 ± 2.5 mm to 25.8 ± 1.7 mm (p < 0.001). The non-athletes on the other hand had a borderline increase in tear secretion from 21.42 ± 2.85 mm to 23.73 ± 2.68 mm (p = 0.08). Also, the TBUT was much improved in the athletes after exercise compared to the non-athletes (17.7 ± 2.7 s vs. 14.8 ± 2.9 s, p = 0.004). Additionally, exercise improved the VA indifferently between the groups, while stereoacuity was unchanged after exercise in either group. Gender had no influence on the differences in the tear function measures between athletes and non-athletes after exercise. The duration of exercise, however, showed a borderline effect on the tear film stability (p = 0.068) after exercise. Our findings support the differential effect of maximal incremental treadmill exercise on tear secretion and tear film stability between athletes and non-athletes. Thus, increased physical fitness and the duration of exercise might be crucial in the improvement of tear function through aerobic exercise.

Optogenetic Inhibition of Nav1.8 Expressing Corneal Afferents Reduces Persistent Dry Eye Pain.

Purpose: The aim of the present study was to investigate the contribution of Nav1.8 expressing corneal afferent neurons to the presence of ongoing pain in lacrimal gland excision (LGE)-induced dry eye. Methods: The proton pump archaerhodopsin-3/eGFP (ArchT/eGFP) was conditionally expressed in corneal afferents using Nav1.8-cre mice. Dry eye was produced by unilateral LGE. Real time place preference was assessed using a three-chamber apparatus. A neutral, unlit center chamber was flanked by one illuminated with a control light and one illuminated with an ArchT activating light. For real-time preference, animals were placed in the neutral chamber and tracked over five 10-minute sessions, with the lights turned on during the second and fourth sessions. In other studies, movement was tracked over three 10-minute sessions (the lights turned on only during the second session), with animals tested once per day over the course of 4 days. A local anesthetic was used to examine the role of ongoing corneal afferent activity in producing place preference. Results: The corneal afferent nerves and trigeminal ganglion cell bodies showed a robust eGFP signal in Nav1.8-cre;ArchT/eGFP mice. After LGE, Nav1.8-cre;ArchT/eGFP mice demonstrated a preference for the ArchT activating light paired chamber. Preference was prevented with pre-application to the cornea of a local anesthetic. Nav1.8-cre;ArchT/eGFP mice with sham surgery and LGE wild-type control mice did not develop preference. Conclusions: Results indicate LGE-induced persistent, ongoing pain, driven by Nav1.8 expressing corneal afferents. Inhibition of these neurons represents a potential strategy for treating ongoing dry eye-induced pain.