Corneal Fluorescein Staining Research Articles

Aprepitant Restores Corneal Sensitivity and Reduces Pain inDED.

This study aims to assess the efficacy of two aprepitant formulations (X1 and X2), in a preclinical model of dry eye disease (DED) induced by benzalkonium chloride (BAK). Two aprepitant formulations were tested on 7 to 8-week-old male mice for their efficacy. In vivo corneal fluorescein staining assessed epithelial damage as the primary end point on days 0, 3, 5, 7, 9, 12, and 14 using slit-lamp microscopy. The DED model was induced with 0.2% BAK twice daily for the first week and once daily for the next week. Mice were randomly assigned to 5 treatment groups: Aprepitant X1 (n = 10) and X2 (n = 10) formulation, 2mg/mL dexamethasone (n = 10), control vehicle X (n = 10), 0.2% hyaluronic acid (n = 10), or no treatment (n = 10). Eye wiping, phenol red, and Cochet Bonnet tests assessed ocular pain, tear fluid secretion, and nerve function. After 7days, the mice were euthanized to quantify leukocyte infiltration and corneal nerve density. Topical aprepitant X1 reduced BAK-induced corneal damage and pain compared to gel vehicle X (P = 0.007) and dexamethasone (P = 0.021). Aprepitant X1 and X2 improved corneal sensitivity versus gel vehicle X and dexamethasone (P < 0.001). Aprepitant X1 reduced leukocyte infiltration (P < 0.05) and enhanced corneal nerve density (P < 0.001). Tear fluid secretion remained statistically unchanged in both the X1 and X2 groups. Aprepitant formulation X1 reduced pain, improved corneal sensitivity and nerve density, ameliorated epitheliopathy, and reduced leukocyte infiltration in male mouse corneas. Aprepitant emerges as a safe, promising therapeutic prospect for the amelioration of DED's associated symptoms.

Efficacy of the combination of cyclosporine and sodium hyaluronate eye drops on dry eye syndrome

Purpose: To investigate the efficacy and adverse effect of cyclosporine combined with sodiumhyaluronate (SH) eye drops on dry eye syndrome (DES).Methods: 148 patients with DES treated in Nanjing Drum Tower Hospital Group Suqian Hospital,Jiangsu Province, China between January 2022 and February 2023 were randomly assigned to control(70 cases) and study groups (78 cases). Control group was treated with SH eye drop (1 drop each onboth eyes 5 - 6 times a day, for 2 months), while study group was treated with both SH (the samedosage and use with control group) and cyclosporine eye drop (1 - 2 drops each for both eyes, 4 - 6times a day, for two months). Tear film stability indices such as schirmer I test (SIT), tear break-up time(BUT) and corneal fluorescein stain (FL) of both groups were analyzed before and after therapy.Results: There was no significant difference in BUT, SIT and FL score between the two groups beforetreatment. Compared with before treatment, BUT and SIT increased significantly (p &lt; 0.05), while FLscore dropped significantly in both groups after treatment (p &lt; 0.05). After treatment, study groupshowed significantly higher BUT and SIT levels, and significantly lower FL score than control group (p &lt;0.05).Conclusion: The combination of cyclosporine eye drops with SH eye drops is effective in treating DES.This combination regimen protects tear film stability, effectively alleviates DES symptoms, improvesocular surface and meibomian gland function, and also increases lacrimal river height, withoutincreasing adverse reactions. Further studies will be required, to provide more evidence for clinicalapplication of this combination regimen.

Evaluation of tear film in patients with AIDS without opportunistic ocular infections in the era of COVID-19: A case-control study.

The assessment of tear film and ocular surface conditions in patients with acquired immunodeficiency syndrome (AIDS) has been poorly studied thus far. We aim to assess tear film parameters, ocular surface characteristics, and dry eye disease (DED) symptoms of patients with AIDS who did not undergo highly active antiretroviral treatment (HAART). This case-control study included 154 age-, sex-, and ethnicity-matched healthy controls and patients with AIDS. All participants underwent comprehensive ocular surface assessment and subjective DED symptomology evaluation. Data were collected between March 2022 and July 2022. HAART-naïve patients with AIDS had a shorter noninvasive tear film breakup time (median 3.76 vs. 8.54 s), thinner tear film lipid layer thickness (median 73.00 vs. 91.00 nm), and lower Schirmer I test values (median 5.00 mm/5 min vs. 12.00 mm/5 min) (all P < 0.001). Moreover, higher corneal fluorescein staining scores (median 1.00 vs. 0.00) and higher upper, lower, and total meibomian gland grades were observed in AIDS patients (all P < 0.05). Negative correlations between the blood viral load and the Ocular Surface Disease Index score ( r = -3.50, P = 0.027) and the Schirmer I test score ( r = -0.374, P = 0.017) were detected in patients with AIDS. Altered tear film status was observed in individuals with HAART-naïve AIDS, even when there were no other ocular symptoms present. Therefore, patients with AIDS should be encouraged to undergo comprehensive ocular surface examinations to detect any subclinical tear film alterations occurring.

Study of IL-17 and Intercellular Adhesion Molecule-1 in Conjunctivochalasis Using Correlation Analysis.

The aim of this study was to observe the expression of interleukin (IL)-17 and intercellular adhesion molecule (ICAM)-1 in conjunctivochalasis (CCH) and to analyze the correlations between cytokines and the severity of CCH. Serum samples were collected from 22 patients with CCH and 18 normal controls (NCs). The Ocular Surface Disease Index, tear film break-up time, Schirmer I test, and corneal fluorescein staining were used to evaluate the ocular surface signs and symptoms. The concentrations of IL-17, IL-23, and ICAM-1 in serum and cellular supernatants were measured by enzyme-linked immunosorbent assays, and the gene expression levels of cytokines were measured by a quantitative real-time polymerase chain reaction. The relationships between serum concentrations of IL-17, IL-23, and ICAM-1 with clinical ocular surface parameters in CCH were analyzed using the Spearman correlation analysis. The concentrations of IL-17 and ICAM-1 in serum and cellular supernatants of CCH were significantly higher than those of NCs (all P < 0.001). The concentrations of IL-23 in serum and cellular supernatants of CCH showed no significant difference from those of NCs ( P > 0.05). The mRNA expression levels of IL-17 and ICAM-1 in conjunctival fibroblasts of CCH were significantly higher than those of NCs (all P < 0.001). The mRNA expression of IL-23 in conjunctival fibroblasts of CCH was higher than that of NCs, without a significant difference ( P > 0.05). Furthermore, the serum concentrations of IL-17 and ICAM-1 were positively correlated with Ocular Surface Disease Index and fluorescein staining (all P < 0.05), and negatively correlated with break-up time and Schirmer I test of CCH (all P < 0.05). The expression levels of IL-17 and ICAM-1 were significantly increased in CCH serum and associated with the disease severity. We postulate that IL-17 and ICAM-1 may play a role in the pathogenesis of CCH. IL-17 and ICAM-1 antagonists may be a potential treatment option for CCH in the future.

A Preservative-Free Approach - Effects on Dry Eye Signs and Symptoms After Cataract Surgery.

To compare the effect of treatment with preservative-free dexamethasone, NSAIDs and trehalose/hyaluronic acid eye drops with the preservative benzalkonium chloride containing dexamethasone and NSAIDs after cataract surgery in dry versus non-dry eyes. In this prospective randomized intervention study, dry eye tests were performed before and 6 weeks after cataract surgery. Patients were considered as having dry eye, SDE (sign of dry eye), if at least one of the following dry eye tests were abnormal; corneal fluorescein staining (CFS), non-invasive keratograph breakup time (NIKBUT) or tear osmolarity. Patients with SDE were randomly assigned to one of two groups. Group 1 patients were treated with dexamethasone and bromfenac eye drops with the preservative benzalkonium chloride (BAC). Group 2 patients were treated with preservative-free dexamethasone and preservative-free diclofenac, as well as a preservative-free lubricant with trehalose and hyaluronic acid both before and after surgery. Patients with normal tear film status acted as the control group (group 3) and received same treatment as group 1. A total of 215 patients were enrolled six weeks after surgery, the number of patients with SDE decreased significantly in groups 1 and 2 (p <0.001). Subjective symptoms and objective measures including osmolarity, NIKBUT, CFS, and tear film thickness (TFT) improved after surgery, tear production remained unchanged, while corneal sensitivity and meibomian gland dysfunction (MGD) parameters worsened. In the control group with normal tear-film status, SDE increased significantly after the surgery (p <0.001). There were no statistically significant differences in tear film parameters between the three groups after surgery. After cataract surgery, patients with mild to moderate dry eyes may experience improved tear film status and reduced symptoms. However, we found no additional beneficial effect on dry eye parameters with treatment with preservative-free dexamethasone, NSAIDs, and lubricants compared to preservative-containing eye drops.

Immediate and Delayed Effects of Punctal Plug Insertion on Tear Meniscus Height in Severe Aqueous-Deficient Dry Eye.

The aim of this study was to assess the immediate and delayed effects of tear punctal occlusion with punctal plugs on tear meniscus height (TMH) in severe aqueous-deficient dry eye (ADDE) disease. Consecutive patients with severe ADDE related to Sjögren syndrome or ocular graft-versus-host disease underwent inferior and superior occlusion with punctal plugs. TMH was measured using the LacryDiag ocular surface analyzer platform before, 10 minutes, and at least 1 month after punctal occlusion. The corneal fluorescein staining (CFS) score was graded with the Oxford scale (from 0 to 5). Ocular symptoms were graded with a visual analog scale (from 1 to 10). We included 24 eyes of 24 patients (mean age 61 ± 9 years; mean follow-up 7 ± 5 months). The mean TMH was 0.19 ± 0.06 mm at baseline and increased significantly to 0.41 ± 0.13 mm (P < 0.001) and 0.46 ± 0.17 mm (P < 0.001) at 10 minutes after punctal plug insertion and at the end of follow-up, respectively. The median CFS score decreased from 3 ± 1 before plug insertion to 1 ± 2 at the end of follow-up (P < 0.001). Many patients (67%; n = 16) reported subjective improvement of symptoms. TMH was negatively correlated with the CFS score and visual analog scale score assessing symptoms. Upper and lower punctal occlusion increased TMH in patients with severe ADDE as soon as 10 minutes after plug insertion. TMH remained stable over time, which led to the relief of symptoms and reduced corneal staining.

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

BackgroundThe 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.MethodsWe 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.ResultsAfter 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-1β, IL-6, and TNF-α levels were improved better than pre-treatment (P = 0.01, 0.03, 0.02, respectively).ConclusionIn 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 registrationRegistration number: NCT06043908.

The Role of IL-6, IL-10, and TNF-α in Ocular GVHD Following Allogeneic Transplantation

ABSTRACT Purpose To figure out the roles of tear inflammatory cytokines in Ocular graft-versus-host disease (oGVHD) symptoms by analyzing tear cytokine levels and related factors. Methods This prospective study involved 27 post-HSCT patients and 19 controls with dry eye disease. Analyses included tear cytokine (IL-6, IL-10, and TNF-α), ocular surface evaluation, and conjunctival impression cell examination. Tear cytokine levels were evaluated in three grades of corneal epithelial lesions. The study also analyzed the correlation between tear cytokine levels and ocular surface parameters. Tear cytokine levels were then used in a Receiver Operating Characteristic (ROC) curve and linear regression model to predict oGVHD related factors. Results IL-6 has good diagnostic efficacy in oGVHD related dry eye. Elevated levels of tear IL-6 and TNF-α were observed in the group with severe corneal epithelial lesions. IL-6 levels were positively correlated with corneal fluorescein staining (CFS), eyelid margin hyperemia, conjunctival lesions, and meibum secretion. IL-6 showed excellent predictive ability with Area Under the Curve (AUC) values all greater than 0.70 (p < 0.05). IL-10 and TNF-α were negatively correlated with the meibomian gland proportion and conjunctival goblet cell (GC) density, while TNF-α was positively correlated with CFS and eyelid margin hyperemia. Conclusion Dry eye symptoms related to ocular GVHD, can be partly diagnosed and assessed using various tear cytokine level detection methods.

Silicone oil as a corneal lubricant to reduce corneal edema and improve visualization during vitrectomy.

To evaluate the efficacy and safety of silicone oil (SO) as a corneal lubricant to improve visualization during vitrectomy. Patients who underwent vitreoretinal surgery were divided into two groups. Group 1 was operated on with initial SO (Oxane 5700) as a corneal lubricant. Group 2 was operated on with initial lactated ringer's solution (LRS) and then replaced with SO as required. Fundus clarity was scored during the surgery. Fluorescein staining was performed to determine the damage to corneal epithelium. Totally 114 eyes of 114 patients were included. Single SO use maintained a clear cornea and provided excellent visualization of surgical image. In group 1, the fundus clarity was grade 3 in 41/45 eyes and grade 2 in 4/45 eyes. In group 2, corneal edema frequently occurred after initial LRS use. The fundus clarity was grade 3 in 19/69 eyes, 2 in 37/69 eyes and 1 in 13/69 eyes (P<0.05). SO was applied in 29 eyes of initial LRS use with subsequent corneal edema, which eliminated the corneal edema in 26 eyes. Corneal fluorescein staining score in group 1 was 0 in 28 eyes, 1 in 11 eyes and 2 in 6 eyes, and 40, 20 and 9, respectively, in group 2 (all P>0.05). The use of SO as a corneal lubricant is effective and safe for preserving and improving corneal clarity and providing clear surgical field during vitrectomy.

Short chain fatty acids inhibit corneal inflammatory responses to TLR ligands via the ocular G-protein coupled receptor 43

PurposeShort chain fatty acids (SCFAs) produced by gut microbiota are known to play primary roles in gut homeostasis by immunomodulation partially through G-protein coupled receptors (GPR) 43. Using mouse models of TLR ligand induced keratitis, we investigated whether SCFAs and GPR43 play any regulatory roles in the pathogenesis of inflammatory responses in the eye. MethodsBoth human and mouse eyes were labeled with a specific antibody for GPR43 and imaged by a laser scanning confocal microscope. Corneal cups from naïve C57BL/6J (B6) and GPR43 knockout (KO) mice were stimulated with TLR ligands in the presence or absence of sodium butyrate overnight and then processed for RT-PCR assay for expression of GPR43 and cytokines. Keratitis was induced by Poly I:C in wild type (WT) B6, GPR43KO and chimeric mice and the disease severity was evaluated by the corneal fluorescein staining test, and infiltrating cell staining and calculating in corneal whole mount. ResultsGPR43 is expressed in both human and mouse eyes and the expression is bidirectionally regulated by TLR ligands and butyrate. Butyrate significantly inhibited inflammation caused by several TLR ligands such as Poly I:C, Flagellin, and CpG-ODN (TLR-3, 5 and 9 agonists, respectively) in WT, but not GPR43KO, mice. Butyrate inhibition of TLR-induced keratitis is mediated by the GPR43 expressed in tissue but not hematopoietic, cells. ConclusionsThis is the first report to demonstrate of the protective effect of SCFAs on microbial keratitis, and the dynamic expression and anti-inflammatory function of GPR43 in the eye. SCFAs can modulate inflammation and immunity in the eye through GPR43.

ER-1 deficiency induces inflammation and lipid deposition in meibomian gland and lacrimal gland

PurposeTo investigated the role of estrogen receptor-1 (ER-1) in maintaining homeostasis in ocular surface. MethodsER-1-knockout (ER-1KO) mice were studied at 4 months of age. The ocular surface was examined using a slit lamp. Histological alterations in the meibomian gland (MG) and lacrimal gland (LG) were observed with H&E staining. Protein levels of P-ERK, peroxisome proliferator-activated receptor gamma (PPAR-γ), p-NFκB-P65, IL-1β, aquaporin 5 (AQP-5), fatty acid-binding protein 5 (Fabp5) and K10 were determined by immunofluorescence and Western blotting. Gene expressions of APO-F, APO-E, K10, ELOVL4, PPAR-γ, SCD-1, and SREBP1 were quantified by qPCR. Conjunctival (CJ) goblet cell alterations were detected by PAS staining. Lipid metabolism in MG and LG was assessed using LipidTox. Apoptosis in MG and LG was analyzed through the TUNEL assay. ResultsBoth male and female ER-1KO mice demonstrated increased corneal fluorescence staining scores. MG showed abnormal lipid metabolism and ductal dilation. LG displayed lipid deposition and reduced AQP-5 expression. CJ experienced goblet cell loss. MG, LG exhibited signs of inflammation and apoptosis. ConclusionER1 is pivotal for ocular surface homeostasis in both genders of mice. ER1 deficiency induces inflammation and lipid deposition to MG and LG, culminating in dry eye-like manifestations on the ocular surface.

Effect of sodium hyaluronate eye drop on tear film stability and tear secretion in patients with rigid gas permeable contact lens associated xerophthalmia

Purpose: To evaluate the impact of sodium hyaluronate eye drops on tear film stability and tear secretion in patients suffering from rigid gas-permeable contact lenses (RGPCL)-associated xerophthalmia.&#x0D; Methods: 88 patients treated at Shangrao Aier Eye Hospital, China with RGPCL-associated xerophthalmia were enrolled in this study from May 2021 to May 2022. They were randomly and equally divided into two groups: a study group (treated with sodium hyaluronate eye drops) and a control group (treated with meibomian gland massage). Tear secretion parameters (lacrimal river width, Schirmer I test (S1t), tear fluid lysozyme content), tear film stability indicators (tear film break-up time, tear film thickness, corneal fluorescein staining score), ocular surface disease index (OSDI), therapeutic effect and incidence of adverse reactions were compared between the two groups.&#x0D; Results: Following the treatment, study group exhibited significantly improved tear secretion compared to control group (p &lt; 0.05). Similarly, tear film stability indicators significantly improved in study group after treatment, accompanied by a reduction in corneal fluorescein staining score (p &lt; 0.05). Although both groups showed decreased OSDI scores after treatment, the reduction was more substantial in study group. Additionally, the therapeutic effect and incidence of adverse reactions were superior in study group compared to control group.&#x0D; Conclusion: The use of sodium hyaluronate eye drops in the treatment of patients with RGPCL-associated xerophthalmia enhances tear secretion, and improves tear film stability and therapeutic outcomes, leading to a reduction in ocular surface disease index and the incidence of adverse reactions. However, this treatment strategy warrants a large-scale clinical trial prior to application in clinical practice.

Sialylated IVIg promotes clinical improvements in a rabbit dry eye model by regulating inflammatory cytokines

Dry eye disease (DED) is caused by a loss of homeostasis of the tear film, which results in visual disturbance, ocular surface inflammation and damage, and neurosensory abnormalities. Although it is prevalent in 5–50% of the global population, there are limited clinical options for its treatment. This study explored the potential use of human intravenous immunoglobulin (IVIg) and its enriched fractions of sialylation, sialylated IVIg (sIVIg), as a treatment for DED. Fifteen female New Zealand white rabbits were topically instilled with 0.2% benzalkonium chloride (BAC) twice daily for five consecutive days to induce experimental dry eye. Saline, 0.4% IVIg, or 0.04% sIVIg eye drops were instilled twice daily for 20 consecutive days. Clinical evaluations, such as non-invasive tear break-up time (NIBUT) and corneal fluorescein staining (CFS), were conducted. mRNA levels of mucin 4, mucin 16, TNF-α, IL-1β, MMP9, IL-10, TGF-β, and CD209 in rabbit conjunctival tissues were examined using reverse transcription polymerase chain reaction (RT-PCR) or quantitative RT-PCR (qRT-PCR). The relationships between CD209 family members in rabbits and various mammalian species were analyzed using a phylogenetic tree. IVIg or sIVIg treatment resulted in clinical improvements in the rabbit DED model. The inflammatory cytokines, TNF-α and IL-1β, were increased and mucin 4 and mucin 16, cell surface-associated mucins, were decreased in BAC-induced dry eye. Following IVIg or sIVIg treatment, inflammatory cytokines decreased, whereas the anti-inflammatory cytokine, IL-10, increased substantially. Moreover, a 10-fold lower sIVIg treatment dose resulted in prolonged IL-10 production, representing a significantly improved DED compared to IVIg. Furthermore, the expression of rabbit CD209 mRNA in the rabbit conjunctiva and its close relationship with primate homologs suggest that it may interact with IVIg or sIVIg to promote IL-10 expression, as previously described in humans. At a lower dosage, sIVIg showed a more efficient improvement in DED, making it a promising new candidate medication for DED.

Effectiveness of acupuncture combined with artificial tears in managing dry eye syndrome: A systematic review and meta-analysis.

Dry eye syndrome is an ocular surface disease with high incidence. Acupuncture combined with artificial tears is effective for treating dry eye syndrome. This study aimed to evaluate the evidence for the efficacy of acupuncture combined with artificial tears in dry eye syndrome by conducting a systematic review and meta-analysis. A systematic online search was performed from the date of database establishment to July 1, 2023. The study groups that addressed acupuncture combined with artificial tears for patients with dry eye syndrome (DES) and the control groups that addressed artificial tears were analyzed. The main outcomes were tear breakup time (BUT) and Schirmer I test (SIT), assessed as previously described. Sixteen randomized or controlled trials met the selection criteria, and 1383 patients with DES were included in this study. The analysis results showed that BUT [Standard mean difference (SMD) = 1.25, 95% confidence interval (CI) (1.14, 1.37), P < .0001], SIT [SMD = 1.55, 95% CI (1.08, 2.02), P < .0001], and corneal fluorescein staining [SMD = -2.08, 95% CI (-2.96, -1.20), P < .00001] significantly improved in the trial groups compared with the control groups. The acupuncture treatment was more effective in reducing the levels of IL-6 (P < .0001) and TNF-α (P < .00001). The overall efficacy rate was better in the trial group than in the control group [odds ratio = 4.09, 95% CI (3.04, 5.51), P < .00001]. However, no significant difference was observed in the ocular surface disease index (P = .15) between the trial and control groups. The results of this study indicated that acupuncture combined with artificial tears could be considered safe, effective to patients with DES.

Effect of Topical Programmed Death-Ligand1 on Corneal Epithelium in Dry Eye Mouse.

Dry eye disease (DED) is a growing health concern that impacts millions of individuals every year, and is associated with corneal injury, excessive oxidative stress and inflammation. Current therapeutic strategies, including artificial tears and anti-inflammatory agents, are unable to achieve a permanent clinical cure due to their temporary nature or adverse side effects. Therefore, here, we investigated the effectiveness of the topical administration of programmed death-ligand 1 (PD-L1) in the mouse model of DED. The model was generated in C57BL/6 mice by excising the extra orbital lacrimal gland and causing desiccation stress with scopolamine injections. Subsequently, either phosphate-buffered saline (3 µL/eye) or PD-L1 (0.5 µg/mL) was topically administered for 10 days. Tear volume was evaluated with phenol red thread, and corneal fluorescein staining was observed to quantify the corneal epithelial defect. Corneas were collected for histological analysis, and the expression levels of inflammatory signaling proteins such as CD4, CD3e, IL-17, IL-1β, pIkB-α, pNF-kB and pERK1/2 were assessed through immunofluorescence and Western blot techniques. Our results demonstrate that desiccating stress-induced corneal epithelial defect and tear secretion were significantly improved by topical PD-L1 and could reduce corneal CD4+ T cell infiltration, inflammation and apoptosis in a DED mouse model by downregulating IL-17 production and ERK1/2-NFkB pathways.

Effects of climate factors and Demodex infestation on meibomian gland dysfunction-associated dry eye diseases.

We examined the effects of climatic factors and Demodex infestations on meibomian gland dysfunction (MGD)-associated dry eye disease (DED) in a cross-sectional study. This study included 123 patients from Tianjin and Chengdu regions, and climate factors and the Air Quality Index (AQI) were recorded for one year. Ocular surface parameters and Demodex infestations were evaluated using various tests. Significant differences in all climatic factors and AQI were observed between Tianjin and Chengdu (P < 0.01), and ocular surface parameters also differed significantly between the two regions (P < 0.05). Temperature, relative humidity, and precipitation positively correlated with tear break-up time (BUT), meibum gland expressibility, and lid margin irregularity but negatively correlated with lissamine green staining scores (P < 0.05). Wind speed and atmospheric pressure positively correlated with corneal fluorescein staining and lissamine green staining but negatively correlated with BUT and lid margin irregularity (P < 0.05). AQI positively correlated with DED symptoms and corneal findings but negatively correlated with tear film stability and meibomian gland characteristics (P < 0.05). Demodex infestation was only positively correlated with meibum quality scores (P < 0.05). Our findings suggest that geographic climates influence ocular surface characteristics in MGD-associated DED, with daily precipitation potentially playing a significant role, and Demodex infestation contributes to meibum gland degeneration.

The Effect of Vidian Neurectomy on the Ocular Surface - The Primary Results from a Six-Month Pilot Study.

To evaluate the effect of vidian neurectomy (VN) on the ocular surface and the possibility of dry eye in the treatment of allergic rhinitis. Twelve participants were recruited in this prospective study. Prior to and after 1 and 6 months of VN, an ocular surface disease index (OSDI) questionnaire was obtained, and the Schirmer's tear test (STT), break-up time (BUT), corneal fluorescence staining (CFS) score, and Keratograph 5M were used to evaluate the ocular surface condition. Two patients (16.67%) met the dry eye diagnosis criteria one month after surgery; however, their symptoms were relieved after to 3-4 months and none of them met the diagnostic criteria for dry eye after six months. Compared with the baseline values, the STT was significantly reduced (P=0.002), while the tear meniscus height (TMH) (P=0.262), break-up time (BUT) (P=0.916), first keratographic tear film break-up time (NK-BUTfirst) (P=0.791), and average keratographic break-up time (NK-BUTave) (P=0.970) did not change significantly 6 months after surgery. The degree of STT decreased from baseline to 6-month and was related to the basic STT (ρ= 0.837, P=0.001) and sex (ρ= -0.584, P= 0.026) but not to age, OSDI score, BUT, NK-BUTfirst, NK-BUTave or CFS (all P>0.05). Among these factors, STT at baseline was confirmed to be a predictor of a decline in tear secretion after surgery (B = 0.731, P<0.001). In this 6-month prospective pilot study, decreased tearing was observed after VN, but this decrease did not increase the possibility of dry eyes.

Corneal complications of ocular GvHD

Corneal fluorescein staining is one of the tests recommended to diagnose and grade ocular graft versus host disease (GvHD) according to the International Chronic Ocular GvHD Consensus Group. Despite superficial punctate keratopathy is the most common corneal manifestation, patients with more severe stages may develop corneal neovascularization, sterile corneal ulceration and even perforation. Previous in vivo confocal microscopy (IVCM) studies reported significant microstructural changes in the cornea of patients with ocular GvHD, including a higher density of dendritic cells and globular immune cells, a network of hyper‐reflective activated keratocytes, and a lower density and higher tortuosity of sub‐basal corneal nerves. Dendritic cells act as antigen‐presenting cells, and play a key role in ocular surface immune homeostasis. Thus, their increased density may be indicative of immune activation and inflammation of the ocular surface in patients with ocular GvHD. Interestingly, Kheirkhah et al. reported higher dendritic cell density in patients with DED owing to systemic immune disease (i.e., Sjögren syndrome and ocular GvHD) compared to patients with DED of other origins. Recently, our group employed a fully automated IVCM analysis system to compare corneal sub‐basal nerve plexus in patients with DED owing to both ocular GvHD and Sjögren syndrome and in healthy control subjects. Although overall patients with DED showed lower density of nerve fibres and branches, shorter nerve fibres and higher fibre width compared to healthy controls, no significant difference was observed between patients with ocular GvHD and Sjögren syndrome for all IVCM metrics. In agreement with this observation, other studies reported no significant difference of IVCM parameters in DED patients with and without ocular GvHD after adjusting for clinical severity of dry eye. This suggests that the ocular surface changes observed by IVCM in ocular GvHD may be possibly reflective of the local disease severity rather than the underlying systemic process.

Long‐term results and persistence of topical cyclosporine a 0.1% treatment in patients with dry eye disease in a tertiary eye centre

Aims/Purpose: This study aims to assess clinical effectiveness, outcome and safety of long‐term topical Cyclosporine A 0.1% Cationic Emulsion (CsA 0.1% CE; Ikervis®) treatment in patients with dry eye disease.Methods: Retrospective chart review of 55 patients (110 eyes) with dry eye disease and severe keratitis treated with Ikervis® since 2016 for at least 12 months without interruption was performed. Study outcomes were median change from baseline in corneal fluorescein staining (CFS, Oxford Grade Scale) score, clinical outcome, treatment discontinuation reason, ocular symptom severity and adverse events (AEs) during long follow‐up.Results: The mean age of patients was 65.96 ± 1.9 years, 81.8% women and 18.2% men. The mean follow‐up was 33.8 ± 19.1 (12–80) months. 43.6% eyes had grade III of CFS at baseline and 4.5% had grade I of CFS at the last follow up. The median CFS score reduced from 2 (1–3) at baseline to 0 (0–1) at the last follow up and this reduction was statistically significant (p &lt; 0.001) from the fourth week. Clinical outcome was defined as active/worsening in 1.8%, stabilization in 14.5%, improvement in 69.1% and resolution in 14.5% of the cases. 65.5% of the patients have continued the treatment without interruption during the whole follow‐up, the treatment discontinuation in 35.5% of the cases were due to improvement (14.5%), AEs (5.5%), patient decision (5.5%), treatment failure (3.6%), other reason (5.5%). Ocular symptom severity was significantly reduced from baseline during the follow up (p &lt; 0.001). In 27.3% cases treatment‐related AEs were reported, most of them (64.7%) were mild.Conclusions: This study shows a long‐term clinical effectiveness and persistence of the topical CsA 0.1% CE treatment in patients with dry eye disease. The significantly reduction of the dry eye symptoms severity from the fourth week of the initiated Ikervis® treatment sustains for a long follow up, and thus definitely improves the quality of life of patients.Reference1. Geerling G, Hamada S, Trocmé S, Ræder S, Chen X, Fassari C, Lanzl I; PERSPECTIVE study group. Real‐World Effectiveness, Tolerability and Safety of Cyclosporine A 0.1% Cationic Emulsion in Severe Keratitis and Dry Eye Treatment. Ophthalmol Ther 2022; 11(3): 1101–1117. doi: 10.1007/s40123‐022‐00487‐x.

Impact of TearCare on Reading Speed in Patients with Dry Eye Disease.

To evaluate the impact of TearCare (TC) treatment on clinical, quality of life, and functional visual outcome metrics in patients with dry eye disease (DED) and meibomian gland disease (MGD). This is a prospective, single-center clinical trial. Adults with MGD and a DED diagnosis and tear break-up time (TBUT) <10seconds were included. All subjects had at least 20/40 vision and no surgery or new treatment for DED within 60 days prior to enrollment. All patients had one baseline visit prior to undergoing TC and one follow-up visit 1 month after TC. At each visit, the meibomian gland secretion score (MGSS), TBUT, and corneal fluorescein staining (KFL) were assessed. DED symptoms were evaluated using the Ocular Surface Disease Index (OSDI) questionnaire, Visual Function Questionnaire 25 (VFQ-25), and the Fatigue Severity Scale. Reading speed was determined through the International Reading Speed Texts (IReST), Minnesota Low Vision Reading Test (MNREAD), and Wilkins Rate of Reading Test (WRRT). Thirty-two subjects were included. The average age was 55.9 years. Sixteen (52%) participants had a clinically significant improvement in reading speed after treatment with TC, defined as >10 words per minute increase in their IReST score. Improvement on the IReST and the MNREAD reached statistical significance (p = 0.012 and p = 0.028, respectively). OSDI scores significantly decreased and VFQ-25 scores significantly increased after TC treatment (p < 0.001). All of the clinical exam parameters showed statistically significant improvements after treatment (p < 0.001). TC is an effective treatment both clinically and with respect to visual function. Patients who had TC exhibited improvements in quality of life and improved reading speed after a single treatment. This treatment should be frequently considered and utilized to reduce the disease burden of DED related to MGD.