Efficacy and retention of silicone punctal plugs for treatment of dry eye in patients with and without ocular graft-versus-host-disease

PurposeTo examine the retention rates and efficacy of silicone punctal plugs for the treatment of dry eye disease (DED) in patients with ocular graft-versus-host-disease (oGVHD) in comparison to dry eye disease due to non-oGVHD etiologies.MethodsWe reviewed the case-records of 864 consecutive patients with DED who were symptomatic despite topical therapy and had silicone punctal plugs placed over an eight-year- period at a single academic center. We compared plug retention rates in oGVHD and non-oGVHD DED patients using Kaplan–Meier analyses. Furthermore, we analyzed changes in objective ocular surface parameters including tear breakup time (TBUT), Schirmer's test, and corneal fluorescein staining (CFS) score in plug-retaining patients at two-, six- and twelve-month follow-up.ResultsMedian age of dry eye patients was 58 years, and 606 (70%) of patients were women. In the cohort, 264 (31%) patients were diagnosed with oGVHD. Plug retention was significantly lower in oGVHD-DED patients compared to non-oGVHD-DED patients (p < 0.0001). We observed significant improvement in CFS scores in plug retaining-oGVHD and non-oGVHD DED patients at all time points. Tear break-up time was significantly prolonged at six- and twelve-months follow-up in non-oGVHD patients, whereas significant change in TBUT in oGVHD patients was recorded only at twelve months post plug placement. Schirmer's score improved significantly in plug retaining-non-oGVHD DED patients at six- and twelve-months follow-up, however no significant change was observed in Schirmer's score in oGVHD DED patients.ConclusionsAn improvement in ocular surface disease parameters was observed in both plug-retaining oGVHD and non-oGVHD DED patients. However, a majority of oGVHD DED patients spontaneously lost their punctal plugs within 90 days of placement. Therefore, regular follow-up after plug placement is recommended to detect plug loss and ensure adequate disease control.     

Ocular pain in ocular graft-versus-host disease patients with neurotrophic keratopathy

PurposeNeurotrophic keratopathy (NK) is a degenerative disorder of the cornea characterized by decreased sensory innervation, epitheliopathy, and impaired epithelial healing. In this study, we assessed ocular pain and quality-of-life-related parameters in ocular graft-versus-host disease (oGVHD) patients with and without NK.MethodsWe included 213 oGVHD patients in this retrospective study, including 29 patients with NK assessed by the Cochet-Bonnet esthesiometer. We evaluated their records for ocular pain assessment survey (OPAS) scores and clinical parameters, including corneal sensation, corneal fluorescein staining (CFS) score, Schirmer's test, tear break-up time (TBUT), and ocular surface disease index (OSDI) score.ResultsoGVHD patients with NK had lower corneal sensation (3.4 ± 1.4 vs. 5.9 ± 0.3; p < 0.0001), higher CFS scores (6.4 ± 4.2 vs. 4.7 ± 4.0; p = 0.01), and lower TBUT scores (1.2 ± 2.1 vs. 2.2 ± 3.1; p = 0.08) compared to oGVHD patients without NK and additionally had significantly higher ocular pain intensity scores (OPAS 24-h average eye pain intensity: 2.0 ± 2.8 vs. 1.1 ± 1.9; p = 0.03). Patients with NK more commonly reported burning (0.2 ± 0.3 vs. 0.3 ± 0.4; p = 0.021) and sensitivity to light (0.2 ± 0.3 vs. 0.3 ± 0.4; p = 0.049) as compared to patients without NK.ConclusionClinical signs of ocular surface disease are worse in oGVHD patients with NK compared to oGVHD patients without NK. These patients additionally experience higher intensity ocular pain and lower quality-of-life-related parameters.     

Tear inflammatory mediators and protein in eyes of post allogenic hematopoeitic stem cell transplant patients

Aim

To analyze tear cytokines levels and their correlation to ocular surface parameters in allogenic hematopoietic stem cell transplants (allo-HSCT) patients.

Prevalence of neurotrophic keratopathy in patients with chronic ocular graft-versus-host disease

PurposeTo determine the prevalence, clinical characteristics, and risk factors associated with neurotrophic keratopathy (NK) in patients with chronic ocular graft-versus-host disease (oGVHD).DesignRetrospective cohort study.MethodsWe performed a chart review of patients diagnosed with chronic oGVHD between January 2015 and December 2018 at a single academic institution and recorded demographic data, systemic and ocular comorbidities, history of hematologic malignancy, transplant characteristics, oGVHD severity scores, and adnexal and ocular examination findings. We determined the prevalence of NK and clinical characteristics associated with NK in these patients. A multivariate logistic regression analysis was performed to determine the risk factors associated with NK in these patients.Main outcome measurePrevalence of NK in chronic oGVHD.ResultsWe identified 213 patients diagnosed with chronic oGVHD following hematopoietic stem cell or bone marrow transplantation from our electronic patient database, and the prevalence of NK was 14%. The mean age of oGVHD patients with NK was 62.6 ± 12.9 years; 48% were women, 19 had unilateral NK, and ten had bilateral NK. In the cohort, 56%, 20%, and 24% eyes of the patients had grades 1, 2, and 3 of NK, respectively. The mean time to diagnose NK after transplantation was 52.9 ± 45.4 months. oGVHD patients diagnosed with NK had a significantly higher NIH oGVHD severity score (p = 0.04) and a lower corneal sensation score (p = 0.0001) than those without NK. Our analyses showed a significantly higher CFS score (p = 0.01) and a trend toward lower Schirmer test scores (p = 0.16) and tear break-up times (p = 0.08) in oGVHD patients with NK. Additionally, we observed a significantly higher prevalence of persistent epithelial defect (p = 0.0001), corneal ulceration (p = 0.0001), and corneal perforation (p = 0.005) in oGVHD patients diagnosed with NK. A logistic regression analysis to determine factors associated with NK showed that a higher NIH oGVHD score (odds ratio [OR] = 2.03, p = 0.026) and history of cataract surgery (odds ratio [OR] = 5.03, p = 0.001) are significant risk factors for NK in oGVHD patients.ConclusionsThe prevalence of NK in chronic oGVHD patients was 14% during the study period. Our analysis shows that oGVHD patients with a higher NIH oGVHD severity score and previous history of cataract surgery are at a higher risk of developing NK and may develop severe sequelae such as persistent epithelial defect or corneal ulceration.     

Autologous platelet-rich plasma eye drop versus artificial tear eye drop for symptomatic dry eye disease: A prospective comparative interventional study

Purpose:To evaluate and compare the efficacy of autologous platelet-rich plasma (aPRP) eye drop and artificial tear (AT) eye drop in moderate to severe symptomatic dry eye disease (DED).Methods:This prospective interventional study included 121 eyes of 61 patients of moderate to severe DED. Patients were divided into aPRP (31 patients) and AT (30 patients) group. Ocular Surface Disease Index (OSDI) score, tear film breakup time (TBUT) (s), corneal fluorescein staining (CFS) score, and Schirmer test score (mm) of both the groups were evaluated and compared pre-treatment and post-treatment at the end of 3 months.Results:The mean age of the aPRP group and AT group was 52.8 ± 12.8 years and 55.5 ± 13.4 years, respectively. At the end of 3 months, OSDI score reduced more in the aPRP group as compared to AT group, and the mean difference (−22.7) was statistically significant (P < 0.001). There was no significant difference in post-treatment Schirmer test score between the two groups (P = 0.44). Post-treatment improvement in TBUT and CFS score in the aPRP group was significantly higher in the aPRP group as compared to that in the AT group (P < 0.05). Bruising at the site of blood withdrawal was noted in two patients in the aPRP group.Conclusion:aPRP is safe and more effective than AT in treating patients with moderate to severe symptomatic DED.     

Developing evidence-based guidance for the treatment of dry eye disease with artificial tear supplements: A six-month multicentre,double-masked randomised controlled trial

PurposeTo assess the six-month therapeutic profiles of lipid and non-lipid-based artificial tear supplements in managing dry eye disease (DED).MethodsNinety-nine participants fulfilling the TFOS DEWS II diagnostic criteria for DED (64% females; mean ± SD age, 44 ± 16 years) were enrolled in a prospective, multicentre, double-masked, parallel group, randomised controlled trial. Participants instilled lipid-based nanoemulsion drops or non-lipid-based aqueous drops for six months, at least four times daily. Symptomology, tear film and ocular surface characteristics were assessed at Days 0, 30, 60, 90, 120, 150 and 180.ResultsSustained reductions in OSDI, DEQ-5, and SANDE symptom scores from baseline were observed from Day 30 onwards in both groups (all p < 0.05) and decreased superior lid wiper epitheliopathy grades from Day 60 onwards (all p ≤ 0.01). Improvements in non-invasive tear film breakup time, and sodium fluorescein and lissamine green staining scores followed from Day 120 onwards in both groups (all p < 0.05). Tear lipid layer grades increased from Day 90 onwards only with the lipid-based drops, and with significantly greater improvement in those with suboptimal lipid layer thickness at baseline (grade ≤3; p = 0.02). By Day 180, 19% of participants no longer fulfilled the diagnostic criteria for DED.ConclusionsOver a six-month treatment period, improvements in dry eye symptomology preceded tear film and ocular surface changes with regular use of both lipid and non-lipid-based artificial tear supplements. Both formulations addressed most mild-to-moderate forms of aqueous deficient and evaporative DED, while evaporative cases benefitted preferentially from lipid-based supplementation. This represents a first step towards mapping DED therapeutic strategies according to disease subtype and severity.     

Corneal fluorescein staining and ocular symptoms but not Schirmer test are useful as indicators of response to treatment in chronic ocular GVHD

Purpose

To evaluate long-term ocular surface clinical signs and symptoms response to therapy in patients with chronic ocular GVHD.

Efficacy of topical cyclosporine 0.05% and osmoprotective lubricating eye drops in treating dry eye disease and inflammation

Purpose:To evaluate the effect of topical cyclosporine 0.05% and osmoprotective lubricating eye drops on patients with dry eye disease (DED) with inflammation as measured by raised tear matrix metalloproteinases (MMP-9).Methods:This prospective study included 106 eyes of 53 patients diagnosed with DED based on any of the following DED criteria (Ocular Surface Disease Index [OSDI] score >12, tear film breakup time [TBUT] <10 s, Schirmer’s I test result <10 mm/5 min, ocular surface staining). Ocular surface inflammation was assessed by assessing MMP-9 positivity from tears of the patients in the study (Inflammadry kit Quidel corporation). Patients were prescribed osmoprotective lubricating eye drops (Osmodrops, Cipla Ltd) four times a day and cyclosporine A 0.05% eye drops (Imudrops, Cipla Ltd) twice a day for 6 months. Efficacy of the formulations was evaluated by OSDI scores, Schirmer’s test, TBUT change, reduction in ocular surface staining, and reduction in MMP-9 levels after 6 months of usage. Check P value and add from resultsResults:After 6 months of topical therapy, improvement was observed in OSDI scores (mean pretreatment: 25.7 ± 12.8, and mean posttreatment: 15.2 ± 8.4), P < 0.001. There was also reduction number of patients who were MMP-9 positive. Out of 75 eyes that tested MMP-9 positive, 70.66% showed reduction in MMP-9 levels P < 0.0001). Ocular surface staining also improved.Conclusion:Topical osmoprotective lubricating eye drops and cyclosporine A 0.05% reduce inflammation in cases of DED, which correlates with improvement in OSDI scores, ocular surface staining, and reduction in inflammation as measured by levels of tear MMP-9.     

The effects of a steam warming eye mask on the ocular surface and mental health

PurposeThe continuous use of warming eye masks improves tear function. In this double-blind randomized controlled trial, we aimed to analyze the effects of warming eye mask use on the ocular surface and mental health.MethodsWe enrolled 86 participants (age range: 23–89 years) from affiliated institutions who were divided into two groups: the warm group that used warming eye masks that generate moist heat at 40 °C for 10 min and the control group that used non-warming eye masks. The participants used the masks for 10 min once daily for 2 weeks. Before and after the intervention, in 79 participants (warm group 39, control group 40), we analyzed the tear break up time (TBUT) and corneal and conjunctival fluorescein staining results in the right eye and Hospital Anxiety and Depression Score (Anxiety: HADS-A, Depression: HADS-D), and Subjective Happiness Scale (SHS) questionnaires. The parameters before and after the intervention were compared via paired-t tests.ResultsThe following variables changed after the intervention: TBUT (warm group: 1.4 ± 2.1 s vs. control group: −0.01 ± 2.38 s), fluorescein staining score (−0.7 ± 1.1 vs.-0.2 ± 1.1), HADS-A (−0.8 ± 3.1 vs. −0.2 ± 2.2), and HADS-D (−1.0 ± 2.4 vs. −0.4 ± 1.9). Significant changes were observed in the TBUT (warm group), fluorescein staining score (warm group), and HADS-D (warm group).ConclusionsUsing a warming eye mask improves not only the ocular surface conditions but also the subjective depression scores.     

Disruption of blood-aqueous barrier in dry eye disease

PurposeTo evaluate level of flare in aqueous humor of dry eye disease (DED) and compare it with normal controls.MethodsIn this cross-sectional study, we compared the anterior chamber flare between 28 patients with DED (the DED group) and 27 normal age- and gender-matched controls (the control group). DED group was divided in Sjӧgren's syndrome dry eye (SDE, n = 10) and non- Sjӧgren's syndrome dry eye (non-SDE, n = 18) groups.ResultsThis study enrolled 55 participants including 28 patients with DED and 27 normal controls. The mean age was 53.4 ± 14.7 years in the DED group and 48.5 ± 14.7 years in the control group (P = 0.086). Mean flare was significantly higher in DED group (12.1 ± 10.2 ph/ms, range 2.7–68.3) compared to the control group (5.0 ± 3.9 ph/ms, range 1.30–30.0, P < 0.001). There was no statistically significant difference in the flare intensity between the Sjӧgren syndrome dry eye (SDE) group (14.5 ± 14.4 ph/ms) and the non-Sjӧgren dry eye (non-SDE) group (10.8 ± 6.9 ph/ms, P = 0.330). A significant correlation was observed between the flare intensity and the ocular surface staining in the SDE group (r = 0.62, P = 0.018).ConclusionThere is a significant increase in aqueous humor flare in patients with DED. Such finding, which is a marker of disruption of blood-aqueous barrier, demonstrates deeper tissue involvement than ocular surface in these patients.     

Corneal higher-order aberrations in eyes with chronic ocular graft-versus-host disease

PurposeChronic ocular graft-versus-host disease (GVHD) is a long-term complication after hematopoietic stem cell transplantation (HSCT) and leads to irreversible visual morbidity due to severe ocular surface impairments including visual disfunction. However, knowledge about the optical function in chronic ocular GVHD is limited because it is difficult to assess quantitative optical function objectively. The development of anterior segment optical coherence tomography has allowed objective quantification of optical function by evaluating corneal higher-order aberrations (HOAs). Therefore, we applied this quantification in chronic ocular GVHD patients and verified the correlation between corneal HOAs and visual acuity.MethodsWe retrospectively reviewed chronic ocular GVHD patients and the recipients after HSCT. Then, analyzed the relationship between visual function and the severity of chronic ocular GVHD.ResultsThe eyes of patients with chronic ocular GVHD had higher corneal HOAs than those of non-GVHD patients (HOAs; 0.481 ± 0.306 vs 0.254 ± 0.084, and 0.917 ± 0.609 vs 0.529 ± 0.130. P < 0.001, and 0.002. 4-mm and 6-mm diameters respectively. Corneal HOAs were correlated with the severity of chronic ocular GVHD (r = 0.436. P < 0.001). Moreover, corneal HOAs were correlated with visual acuity, especially in eyes with severe chronic ocular GVHD cases (HOAs; 4-mm r = 0.636. P = 0.036. Total 6-mm r = 0.871. P =<0.001).ConclusionsWe succeed to assess the objective value in the optical function of the chronic ocular GVHD. Quantification of corneal HOAs could be an objective evaluation to assess optical function in eyes with chronic ocular GVHD.     

Correlations between tear fluid and aqueous humor cytokine levels in bullous keratopathy

PurposeTo evaluate the correlation between tear fluid and aqueous humor (AqH) cytokine levels in eyes with bullous keratopathy (BK) and with normal endothelium.MethodsThis prospective consecutive case-series study included 71 eyes of 71 patients: 31 eyes with BK, 18 eyes with non-BK corneal diseases, and 22 eyes with uncomplicated cataract (healthy controls). Total protein and cytokine (interleukin [IL]-1α, IL-1β, IL-4, IL-6, IL-8, IL-10, MIP-1α, MIP-1β, monocyte chemotactic protein [MCP]-1, E-selectin, P-selectin, soluble intercellular adhesion molecule [sICAM]-1, and IP-10) levels in the tear fluid and AqH were measured using multiplex beads immunoassay. The correlations between tear and AqH cytokine levels were assessed.ResultsThe AqH protein level was significantly higher in BK eyes (1.09 ± 0.08 mg/mL) than in non-BK (0.63 ± 0.11, P = 0.0004) and healthy control (0.62 ± 0.06, P = 0.0002) eyes. The tear total protein and IL-4 levels were significantly higher in the BK group compared to healthy controls (P = 0.0374 and 0.0032, respectively). The AqH IL-8 and sICAM-1 levels were significantly higher in the BK group compared to controls (P = 0.0001 and 0.0083, respectively). In BK eyes, the tear IL-4 level was significantly correlated with the MCP-1(r = 0.563, P = 0.001) and total protein (r = 0.589, P = 0.001) AqH levels. The tear IL-8 level was significantly correlated with the MCP-1(r = 0.598, p = 0.001) and IL-4 (r = 0.781, p < 0.0001) AqH levels in BK eyes. However, no significant correlations were found between tear and AqH cytokine levels in non-BK and healthy controls eyes.ConclusionsThe tear cytokine levels are correlated with those of AqH only in BK, but not in non-BK and healthy controls.     

Sex and age differences in symptoms and signs of dry eye disease in a Norwegian cohort of patients

PurposeTo investigate sex and age differences in symptoms and signs in a Norwegian clinic-based cohort of patients with dry eye disease (DED).MethodsVisitors at the Norwegian Dry Eye Clinic were examined using Ocular Surface Disease Index (OSDI) questionnaire score, tear osmolarity, tear break-up time (TFBUT), ocular surface staining, corneal sensitivity, Schirmer I test, and meibum expressibility (ME) and quality (MQ). A diagnosis of DED was made by an ophthalmologist based on symptoms and signs, and only DED patients were enrolled in the study: 1823 patients (338 males; mean age 51.2 ± 16.2 years; 1485 females; mean age 52.5 ± 16.0 years). The patients were divided into age subgroups: 20–39 years, 40–59 years and ≥60 years. Sex differences in the aforementioned tests were analyzed. Values were reported as mean ± standard deviation (SD), and intergroup comparisons were performed using Mann-Whitney U test. Multiple regression was used to analyze sex and age influences on symptoms and signs.ResultsWhen patients of all ages were analyzed, females had increased osmolarity, shorter TFBUT, reduced MQ and ME and higher corneal sensitivity. OSDI, Schirmer I test, ocular surface staining and corneal staining were not significantly different between the sexes. Only with TFBUT and ME were the sex difference present in all age subgroups. Multiple regression showed that all parameters were influenced by either sex or age, but only TFBUT and ME were influenced by both sex and age. (all p < 0.05).ConclusionsSex and age differences in dry eye were most consistent in TFBUT and ME, that indicate differences in meibomian gland functionality. Sex and age subgroup stratification is important in future studies investigating DED in other populations.     

Meibomian gland dysfunction is the primary determinant of dry eye symptoms: Analysis of 2346 patients

PurposeTo determine relative contributions of various ocular surface clinical signs and predisposing factors to the magnitude of dry eye symptoms.MethodsClinical audit data were prospectively collected for newly referred dry eye patients. All 2346 patients had an initial visit evaluation of the Ocular Surface Disease Index (OSDI), and a detailed ophthalmic examination including tear breakup time (TBUT), ocular surface fluorescein staining, Schirmer's I test. Among the participants, 1414 had number of liquid meibum expressing glands (NLMEG) evaluated on standard force expression. Other variables collected included history of glaucoma or glaucoma surgery, and history of allergies.ResultsIn patients aged 46.2 ± 14.8 years, 77.4% were women and 87.1% Chinese. The mean ± SD OSDI was 35.2 ± 21.7. On univariate analysis, higher OSDI was associated with glaucoma diagnosis (p = 0.003), glaucoma surgery (p = 0.002), greater temporal corneal staining (p = 0.002), reduced NLMEG (p < 0.001), and higher inferior forniceal papillary grade (p < 0.001). OSDI was not significantly associated with gender, TBUT, Schirmer's I test values, or the use of cyclosporine eyedrops. On multivariate regression, higher OSDI scores were associated with fewer NLMEG (p = 0.002) and increased lower eyelid forniceal papillary grading (p = 0.002). Corneal staining, glaucoma status and glaucoma surgery were not significantly associated with OSDI. Logistic regression showed that severe symptoms (OSDI>32) was associated with <2 NLMEG [OR(95%CI): 1.34(1.08–1.66)], and presence of inferior eyelid forniceal papillae [1.50(1.17–1.91)].ConclusionsMeibomian gland dysfunction (MGD) and lower forniceal papillary reaction had significant contributions to the severity of symptoms, in contrast to traditional dry eye signs. MGD should be objectively assessed and treated to improve symptoms.     

The physical and mental burden of dry eye disease: A large population-based study investigating the relationship with health-related quality of life and its determinants

PurposeThis large cross-sectional population-based study investigated the relationship between dry eye disease (DED) and health-related quality of life (HR-QoL).MethodsDry eye and HR-QoL were assessed in 78,165 participants (19–94 yrs, 59.2% female) from the Dutch population-based Lifelines cohort, using the WHS and the SF36 questionnaire, respectively. Logistic regression was used to assess the relationship between DED and below median Physical Component Summary (PCS) and Mental Component Summary (MCS) score, corrected for age, sex, education, BMI, and 52 comorbidities.ResultsOverall, 8.9% of participants had DED. Participants with DED had an increased risk of low PCS (OR 1.54 (95% CI 1.46–1.62)) and MCS scores (OR 1.39 (95% CI 1.32–1.46)), corrected for age and sex. This risk remained significant after correction for comorbidities (P < 0.0005). Increasing DED symptom frequency was associated with decreasing HR-QoL (P < 0.0005). Undiagnosed DED subjects had a significantly increased risk of low mental HR-QoL with increasing dry eye symptoms compared to diagnosed subjects (P < 0.0005). Compared to allergic conjunctivitis, glaucoma, macular degeneration and retinal detachment, DED showed the highest risk of low HR-QoL. Compared to other common systemic and chronic disorders, such as depression, rheumatoid arthritis, and COPD, DED was distinctive by having a substantial reduction in both PCS and MCS.ConclusionDED is associated with substantial reductions in both physical and mental HR-QoL, also after correction for associated comorbidities. Not having a diagnosis is associated with worse mental HR-QoL in subjects with severe DED. Our results underline the importance of recognizing dry eye as a serious disorder.     

Multicenter prospective validation study for international chronic ocular graft-versus-host disease consensus diagnostic criteria

PurposeTo validate the international chronic ocular graft-versus-host disease (GVHD) diagnostic criteria (ICCGVHD) compared to the National Institute of Health diagnostic criteria 2014 (NIH2014) for chronic ocular GVHD.MethodsBetween 2013 and 2019, the study enrolled 233 patients with or without chronic ocular GVHD combined with the presence or absence of systemic chronic GVHD in an internationally prospective multicenter and observational cohort from 9 institutions. All patients were evaluated for four clinical parameters of ICCGVHD.ResultsThe relation between the ICCGVHD score (0-11) and NIH2014 eye score (0–4) was relatively high (r = 0.708, 95% CI: 0.637–0.767, p < 0.001). The sensitivity and specificity of ICCGVHD for NIH 2014 for 233 patients were 94.3% (95% CI: 89.6%–98.1%) and 71.7% (95% CI: 63.0–79.5%), respectively (cutoff value of the ICCGVHD score = 6). The positive predictive value was 77.1% (95% CI: 71.1%–82.1%), and the negative predictive value was 87.0% (95% CI:81.6–92.5%). For the patients with systemic GVHD (n = 171), the sensitivity and specificity were 94.2% and 67.2%, respectively (ICCGVHD-score cutoff value = 6). By receiver operating characteristic (ROC) curve analysis, the area under the curve (AUC) was 0.903 (95% CI: 0.859–0.948). For patients without systemic GVHD (n = 62), the sensitivity and specificity were 100% and 76.7%, respectively (ICCGVHD-score cutoff value = 6). The AUC was 0.891 (95% CI 0.673–1.000).ConclusionsGood sensitivity, specificity, predictive value and correlation were found between ICCGVHD and NIH2014. ICCGVHD scores ≥6 can be useful to diagnose ocular GVHD with or without systemic GVHD for clinical research.     

NLRP12- and NLRC4-mediated corneal epithelial pyroptosis is driven by GSDMD cleavage accompanied by IL-33 processing in dry eye

PurposeDry eye disease (DED) is a common and multifactor-induced autoimmune ocular surface disease. Environmental factors, such as desiccating stress (DS) and hyperosmolarity, affect the corneal epithelium to induce ocular surface inflammation in DED. We aimed to explore the potential mechanisms by which innate immunity and pyroptosis are initiated in the mucosal epithelium in response to environmental stress.MethodsExperimental dry eye was established in C57BL/6 J mice and genetic mice on the background of C57BL/6 J mice by subcutaneous injection of scopolamine and exposure to a desiccating environment. SDHCEC cell line was subjected to hyperosmolarity stress (450 mOsM). The phenol red thread tear test and corneal epithelial defects evaluation were used as assessments of severity of DED. RNA-sequencing, quantitative real-time PCR, western blotting and immunofluorescence staining were performed in this study.ResultsLoss-of-function studies indicated that genetic deletion of GSDMD alleviates DS-induced corneal epithelium defects, and GSDMD is needed for IL-33 processing. We further found that NLRP12 collaborates with NLRC4 inflammasome to initiate GSDMD-dependent pyroptosis, which requires TLR4-induced caspase-8 (CASP8) activation in the mucosal corneal epithelium in response to DS.ConclusionsThese findings provide compelling evidence that GSDMD-dependent pyroptosis plays a pivotal role in DED. A novel mechanism involving NLRP12 and NLRC4 inflammasomes-induced GSDMD-dependent pyroptosis, accompanied by IL-33 processing is responsible for ocular surface epithelial defects in response to environmental stress. GSDMD is required for IL-33 processing and the subsequent amplification of inflammatory cascades. These findings reveal novel therapeutic targets for treating DED.     

Eyelid metrics assessment in patients with chronic ocular graft versus-host disease

Purpose

To assess eyelid metrics in the setting of chronic ocular graft versus-host disease (oGVHD), and to further correlate them with hematological and ocular characteristics.

Assessment of dry eye disease in N95 versus surgical face mask wearers during COVID-19

Purpose:Investigating the effect of different face masks on dry eye disease (DED) among healthcare workers during the COVID-19 pandemic.Methods:This was a comparative, cross-sectional study. Participants were included into two groups: group 1 (n = 30) wore surgical masks, and group 2 (n = 30) wore N95 masks with face shields. Demographic and ocular surface disease index questionnaires (OSDI) were performed. In addition, Tear break-up time (TBUT), corneal and conjunctival fluorescein staining, and meibography to assess meibomian gland loss (MGL) were performed on all participants. Independent T-test was used to compare continuous parameters and Chi-square test for categorical variables. The relationship between continuous variables was tested using bivariate Pearson correlation.Results:Sixty healthcare workers participated in this study (36 females and 24 males). The mean (±SD) age of the surgical mask and N95 groups was 35.33 (±14.94) and 36.63 (±10.64) years, respectively. Both masks caused dryness according to TBUT, MGL, and OSDI scores. DED per DEWS II definition was observed in 14 (46.7%) and 16 (53.3%) patients in groups 1 and 2, respectively. Comparing the two groups, N95 mask caused significantly more dryness according to TBUT (P = 0.042) and fluorescein staining (P = 0.038 for the right eye and P = 0.015 for the left eye).Conclusion:Physicians should be aware of the potential dry eye signs secondary to face mask wear during the COVID-19 pandemic. Further attention should be taken in patients who suffer from preexisting dry eye syndrome and in patients who undergo intraocular operations.     

The Role of Multisystem Disease in Composition of Autologous Serum tears and ocular surface symptom improvement

PurposeAutologous serum tears (AST) contain growth factors and vitamins similar to those in healthy tears and are an effective treatment option for ocular surface disease. This study determined the differences in composition of AST in patients with systemic diseases versus patients with localized ocular surface diseases and the effects on ocular surface symptom improvement.MethodAn observational study was performed on 53 patients with either systemic diseases (Group I) or localized ocular surface diseases (Group II) who were prescribed AST. Concentrations of epidermal growth factor (EGF), interleukin 8 (IL-8), fibronectin, vitamin A, and tumor necrosis factor-α (TNF-α) were determined through ELISA assays from patients in both groups. The Ocular Surface Disease Index (OSDI) scores were calculated prior to and 6 weeks after initiation of treatment with AST for new patients.ResultsThe average concentration of EGF in Group I (29.39 pg/ml ± 52.85 pg/ml) was significantly lower than in Group II (88.04 pg/ml ±113.75 pg/ml) (p < 0.05). Levels of fibronectin, IL-8, and vitamin A were similar in both groups. There was a 24% reduction in OSDI score 6 weeks after initiation in Group I compared to a 36% reduction reported in Group II (p = 0.065). The OSDI score was reduced significantly after the treatment in all subjects (p = 0.002).ConclusionSerum tears are a promising therapy for management of ocular surface disease and associated symptoms. The differences between levels of EGF in patients with localized ocular surface disease and systemic inflammatory disease may account for differences in therapeutic outcome.