Conjunctival Staining Scores Research Articles

Short-term variability in ocular biometry and the impact of preoperative dry eye.

This study aimed to investigate the short-term variability of ocular biometric measurements and to analyze the factors associated with high variability of biometric values in patients with cataract. This retrospective study included 60 eyes of 60 patients who underwent ocular biometry twice with the IOLMaster 700 (March to November 2023). Ocular surface parameters included tear film break-up time (TBUT), corneal and conjunctival staining scores (CSS/ConSS). Refractive surprise was defined as a mean absolute error exceeding 0.5 diopter (D). Participants included 22 men and 38 women with a mean age of 70.6 ± 8.4 years. The variability of mean keratometric (K) values and astigmatism showed notable variability compared to axial length (mean K: 0.18 ± 0.17D, astigmatism: 0.21 ± 0.26D, axial length: 0.01 ± 0.01mm). A decreased TBUT and increased CSS were significantly associated with high variability (≥ 0.25D) of mean K (p = 0.040/0.008). The high K variability group (≥ 0.25D) revealed a significantly higher incidence of refractive surprise (> 0.5D) compared with the low K variability group (< 0.25D) (45.5%/17.9%, p = 0.037). Preoperative lower TBUT and higher CSS influenced the variability of K values in ocular biometry and may be related with postoperative refractive surprise due to erroneous K values.

Tolerability of Diquas LX on tear film and meibomian glands findings in a real clinical scenario.

Long-acting diquafosol ophthalmic solution (DQS-LX) has significant advantages regarding patient adherence owing to the reduced frequency of required eye drops; however, some patients prefer conventional diquafosol ophthalmic solution (DQS) over DQS-LX. Herein, to clarify the characteristics of patients according to their preference for ophthalmic solutions, dry eye (DE) and meibomian gland (MG) findings were retrospectively investigated. This study enrolled 341 patients with DE (mean age, 62.1 ± 11.7 years) treated at the Itoh Clinic between November 8, 2022, and July 31, 2023, who switched from DQS to DQS-LX. Patients were divided into two groups: those who continued DQS-LX administration (DQS-LX group) and those who wished to revert to conventional DQS (DQS group). Data regarding subjective symptoms assessed using the Standard Patient Evaluation of Eye Dryness (SPEED) questionnaire, tear film breakup time (BUT), tear meniscus height (TMH), corneal and conjunctival fluorescein staining (CFS), conjunctival hyperemia/papilla, meiboscore, plugging, vascularity, meibum grade, and Schirmer's score at the time of DQS-LX switch were evaluated. Of the 341 patients, 31 (9.1%) wished to revert to conventional DQS. In total, 16 eyes of 16 patients in the DQS group and 32 eyes of 32 patients in the DQS-LX group-for whom complete data were available-were included in the analysis. The DQS-LX group had higher SPEED scores, lower TMHs (P < 0.001, respectively), shorter FBUTs, greater CFS findings, larger meibum grades, lower Schirmer scores, and more pluggings compared with the DQS group (P = 0.005, 0.001, 0.001, 0.046, 0.003, respectively). Meiboscores and vascularity did not differ significantly between the two groups (P = 0.73 and 0.39, respectively). In conclusion, patients with low tear film volume and DE complicated by moderate or severe meibomian gland dysfunction (MGD) preferred DQS-LX, while those with allergic findings preferred conventional DQS.

Longitudinal Analysis of Tear Cytokine Ratios in Association with Dry Eye Signs and Symptoms in the Dry Eye Assessment and Management (DREAM) Study

Purpose To extend cross-sectional data on cytokine ratios (CRs) in dry eye disease (DED) signs by investigating longitudinal change in pro- to anti-inflammatory CRs and associations with change in DED signs and symptoms. Methods Secondary analysis of fifty-four subjects [mean age 57.3 (SD 13.2) years, 85.2% female; 68.5% white] with ≥ 4 uL pooled tear volumes at months 0, 6, and 12. Pro-inflammatory (IL-1b, IL-6, IL-8, IL-17A, IFN-g, and TNF-a) to anti-inflammatory (IL-6, IL-10) cytokine ratios (CR) were calculated. DED signs (corneal and conjunctival staining scores, tear break-up time, Schirmer test, Meibomian gland plugging, tear osmolarity, composite sign severity score) and symptoms [Ocular Surface Disease Index (OSDI)] were measured. Changes over time in DED signs, symptoms, and CRs were evaluated using longitudinal models. Correlations between changes in CR and changes in DED signs and symptoms were evaluated using Spearman correlation coefficients (rho). Results DED signs which improved over time (p < 0.001) included corneal and conjunctival staining score, tear break-up time, tear osmolarity, and composite sign severity score. Using IL-10 as anti-inflammatory, changes in corneal and conjunctival staining and composite severity score significantly correlated with changes in pro- to anti-inflammatory CRs from month 0 to 6 (|rho|: 0.29-0.45, p: 0.003-0.04) but not between month 0 to 12 (|rho|: 0.01 to 0.24, all p > 0.08). DED symptoms decreased across one year (p < = 0.001) for all OSDI measures; these changes did not correlate with changes in CRs (|rho|: 0.00 to 0.29, all p > 0.04). Conclusions Improvement in some DED signs across one year correlated weakly with decreases in pro- to anti-inflammatory CRs, in alignment with the understanding of DED as inflammatory. CRs may provide greater insight than absolute tear cytokine concentrations as possible DED biomarkers. Additional studies that provide standardized clinical information and tear collection and analysis are needed to validate CRs in DED.

Sleep Disturbances and Dry Eye Symptoms and Signs, Systemic Conditions, and Inflammatory Markers in the Dry Eye Assessment and Management Study

Purpose: To investigate the association between sleep disturbances, dry eye disease (DED) severity, and DED risk factors. Methods: We conducted a secondary analysis of the Dry Eye Assessment and Management (DREAM) study, a randomized trial of 535 patients with moderate-to-severe DED. Participants self-reported sleep disturbances at baseline. DED symptoms were assessed using the Ocular Surface Disease Index and Brief Ocular Discomfort Index. DED signs were assessed using tear film break-up time, Schirmer test, corneal and conjunctival staining, tear osmolarity, and meibomian gland dysfunction assessment. Immune cells were assessed using conjunctival impression cytology. Outcomes were compared between participants with ongoing and no history of sleep disturbances, adjusting for confounders. Results: The mean age was 58 years, and 81% were women. Ongoing sleep disturbances (n = 113) were significantly associated with older age (mean 60.5 vs. 57.4; P = 0.03), smoking (39.8% vs. 28.7%; P = 0.02), and DED treatment. Systemic conditions associated with sleep disturbances included thyroid dysfunction (26.5% vs. 15.7% P = 0.007), irritable bowel (18.6% vs. 5.4%; P &lt; 0.0001), osteoarthritis (38.9% vs. 21.6%; P = 0.0007), and depression (30.1% vs. 11.5%; P &lt; 0.0001). Sleep disturbances were associated with lower conjunctival staining scores (2.46 vs. 2.77; P = 0.03) and higher concentrations of dendritic cells in ocular surface white blood cells (12.0% vs. 8.1%; P = 0.01). Conclusions: Sleep disturbances were associated with older age, smoking history, systemic diseases, and higher dendritic cell concentration among patients with moderate-to-severe DED. These findings support further investigation of sleep disturbances as a comorbidity of patients with DED. Additional research is needed to understand the mechanisms behind this relationship.

Efficacy and Clinical Outcome of Single and Combined Therapies for Refractory Meibomian Gland Dysfunction: Probing, Intense Pulsed Light, and Thermal Pulsation Treatments

Background: Refractory meibomian gland dysfunction (MGD) is a prevalent condition characterized by chronic functional abnormalities of the meibomian glands, leading to altered tear film and ocular discomfort despite medical treatments. Traditional management strategies include various single-modality treatments, although there is growing interest in the efficacy of combined therapies. Aim: The aim of this study was to evaluate the efficacy of regimens used individually and in combination for the treatment of refractory MGD. Methods: This retrospective study involved pre- and posttreatment evaluations of the ocular surface and symptoms in patients with refractory MGD. Treatments included meibomian gland probing (MGP), intense pulsed light (IPL) therapy, thermal pulsation (LipiFlow), IPL + MGP, and MGP + LipiFlow. Results: In total, 325 eyes of 241 patients with refractory MGD were assessed. The MGP group showed significant improvements in the ocular surface disease index (OSDI), tear meniscus height (TMH), corneal and conjunctival staining, lid wiper epitheliopathy (LWE), and meibomian gland expression (MGX) score. The IPL group showed significant improvements in OSDI, TMH, redness, conjunctival staining, and MGX score. IPL + MGP resulted in significant improvements in corneal and conjunctival staining, LWE, and MGX score, while LipiFlow significantly improved conjunctival staining, LWE, and MGX score. No significant improvements were observed in the MGP + LipiFlow group. Conclusion: IPL or MGP alone could alleviate the signs and symptoms of refractory MGD, while LipiFlow and IPL + MGP could improve the ocular surface parameters. However, no significant improvements were observed with MGP + LipiFlow. These findings provide a valuable guide for ophthalmologists for the selection of effective treatment modalities for refractory MGD, suggesting a potential advantage of combined IPL + MGP to maximize therapeutic benefits.

A randomised study comparing performance and safety of Eyestil Plus® vs Vismed Multi® in moderate-to-severe dry eye syndrome patients.

This clinical investigation compared the performance and safety of Eyestil Plus® (SIFI) and Vismed Multi® (TRB Chemedica) for reducing keratitis lesions in moderate-to-severe dry eye disease (DED) patients. This was a randomised, double-blind, multicentre investigation. 96 adults (>18 years of age) with moderate-to-severe DED received Eyestil Plus® (N = 48) or Vismed Multi® (n = 48) 6 times daily for 3 months. The primary objective clinical performance after 1 month as global corneal and conjunctival staining scores. The secondary objectives were clinical performance after 3 months, tear film stability (tear break up time (TBUT), tear production (Schirmer test), patient-reported outcomes (PROs), investigator satisfaction, and safety. 96 participants were randomised to receive the clinical investigations' treatments, 82.3% of them were female and their mean age was 65.8 years. The non-inferiority of Eyestil Plus® for moderate-to-severe DED was demonstrated at 1 month. No statistical difference was found for any of the study's objectives: change at 1 and 3 months of the global corneal and conjunctival staining score (p-value = 0.506 and 0.661, respectively), change at 1 and 3 months (p-value = 0.538 and 0.302) for TBUT test; change at 3 months for Schirmer test (p-value = 0.540). There were no changes for PROs either. Investigator satisfaction was high for both products. 16.6% of the participants experienced adverse events. This clinical investigation showed the non-inferiority of Eyestil Plus® compared to Vismed Multi® regarding performance and safety in a moderate-to-severe DED population.

Effects of combined intense pulsed light and cyclosporine 0.05% eyedrops in ocular surface matrix metalloproteinase-9 levels in patients with moderate-to-severe MGD.

To investigate the changes in meibomian gland dysfunction (MGD) and tear matrix metalloproteinase-9 (MMP-9) levels in patients with moderate-to-severe MGD after combined treatment with intense pulsed light (IPL) therapy and cyclosporine 0.05%. Thirty-six patients concurrently treated with IPL and cyclosporine 0.05% ophthalmic drops were retrospectively enrolled. Tear break up time (TBUT), corneal and conjunctival staining scores, Schirmer test, and ocular surface disease index (OSDI) questionnaire responses were recorded. Meibum quality, consistency, and eyelid margin telangiectasia were evaluated. MMP-9 levels were examined by the positivity and signal intensity of red lines (scored 0-4). IPL was performed four times with a vascular filter at 2-week intervals, followed by a 1-month follow-up after treatment cessation. Immediately after each IPL treatment, gentle meibomian gland expression was performed in both the upper and lower eyelids using meibomian gland expressor forceps. TBUT (1.88 ± 1.02s to 3.12 ± 1.08s, p < 0.001), corneal and conjunctival staining (6.19 ± 2.11 to 3.12 ± 1.89, p < 0.001), Oxford staining grade (2.66 ± 0.89 to 1.35 ± 0.76, p < 0.001), and OSDI (52.97 ± 21.86 to 36.36 ± 22.45, p < 0.001) scores significantly improved after the combined treatment. Meibum quality, consistency and lid margin telangiectasia showed significant post-treatment improvement in both the upper and lower eyelids. MMP-9 positivity showed a significant decrease (97-69%, p = 0.026) with a reduction in signal intensity (2.72 ± 0.87 to 2.09 ± 0.95, p = 0.011). The combination of IPL therapy and 0.05% cyclosporine eye drops effectively treats moderate-to-severe MGD by reducing symptoms and signs of MGD and by decreasing ocular surface MMP-9-associated inflammation.

Advantages of Lissamine Green Vital Staining as an Endpoint in Dry Eye Clinical Trials.

The absence of a standardized diagnostic method for clinical signs of Dry Eye Disease (DED) complicates clinical trials for future treatments. This paper evaluated Lissamine Green (LG) conjunctival staining as a valid, stable and modifiable endpoint for both clinical practice and clinical trials. Screening and pre-randomization data from two identically designed clinical trials for DED resulted in a pooled dataset of 494 subjects. Inclusion was based on reported symptoms, lissamine green (LG) conjunctival staining, Fluorescein (Fl) corneal and conjunctival staining, and Schirmer's Test (ST). Outcome measures were assessed based on the modifiability of LG staining to exposure to a Controlled Adverse Environment (CAE®), correlation of LG to Fl staining, relative variation of LG staining scores and Schirmer test scores, and the correlation of LG staining with symptom scores. The modifiability of LG conjunctival staining to environmental exposure was demonstrated, with nasal LG and FL staining displaying the most similar percent change. Nasal LG conjunctival staining scores for subjects with ST scores of less than 8mm were significantly higher than for subjects with ST greater than 8mm. LG staining scores were more consistent (25% change from baseline threshold) than ST scores. Finally, statistically significant correlations were found between LG staining and a number of symptom scores. This evaluation demonstrates the superiority of the utilization of a clinical endpoint focused on ocular surface damage. The reproducibility and modifiability of LG conjunctival staining to controlled adverse environment, coupled with its significant correlation with symptoms, positions it as an exemplary clinical sign endpoint for clinical management and in clinical trials. Our findings advocate for the adoption of LG conjunctival staining as a primary endpoint in both clinical research and drug development, offering a more effective means of identifying and addressing ocular surface damage in the realm of DED.

Clinical ocular surface characteristics and expression of MUC5AC in diabetics: a population-based study.

To investigate the clinical characteristics and the expression of mucin 5AC (MUC5AC) in in diabetic and non-diabetic subjects with or without dry eye disease. A total of 399 participants (796 eyes) aged 50-80 years were enrolled in this study. Participants were divided into 4 groups: non-diabetic without dry eye group (normal group), non-diabetic with dry eye group, diabetic without dry eye group and diabetic with dry eye group. Demographic information, fasting plasma glucose (FBG), and glycated haemoglobin A1C (HbA1C) data were collected. Additionally, ocular surface disease index (OSDI) questionnaire, signs of dry eye, tear osmolarity, and meibomian glands were evaluated. Tear MUC5AC expression and conjunctival goblet cells density (GCD) were tested. Compared with non-diabetic with dry eye group, diabetic with dry eye group showed significantly lower tear film osmolarity (TFO), but higher corneal fluorescein and conjunctival lissamine green staining scores. In comparison with diabetic without dry eye group, diabetic with dry eye group showed significantly higher TFO, corneal fluorescein and conjunctival lissamine green staining scorers. The MUC5AC concentration and GCD of diabetic with dry eye group was significantly lower than those of the non-diabetic with dry eye group. Diabetic subjects with higher HbA1c levels (≥7.8%) showed higher TFO and shorter fluorescein tear break time. Diabetics with dry eye exhibited notably higher corneal fluorescein and conjunctival lissamine green staining scores. Conjunctival goblet cells and MUC5AC were significantly reduced in diabetics. Higher TFO was associated with the duration of diabetes and HbA1c levels.

Discriminative performance of ocular surface staining and lid wiper epitheliopathy in dry eye disease: An investigator-masked, prospective registry-based, diagnostic accuracy study

PurposeTo evaluate the diagnostic performance of corneal and conjunctival staining, and lid wiper epitheliopathy (LWE) in detecting dry eye disease, as defined by the global consensus Tear Film and Ocular Surface Society Dry Eye Workshop II (TFOS DEWS II) criteria. MethodsA total of 2066 community residents (1285 females; mean ± SD age, 40 ± 19 years) were recruited in an investigator-masked, prospective registry-based, diagnostic accuracy study. Dry eye symptomology and ocular surface parameters were assessed in a single clinical session. The Sjögren's International Collaborative Clinical Alliance (SICCA) corneal and conjunctival staining scoring and Korb lid wiper epitheliopathy (LWE) grading were evaluated by an independent masked assessor. ResultsOverall, 807 (39 %) participants fulfilled the TFOS DEWS II criteria for dry eye disease, of which 178 (9 %) participants were classified as moderate-to-severe disease. The discriminative abilities of superior and inferior LWE (C-statistics, 0.724 and 0.712, respectively) were greater than corneal and conjunctival staining (C-statistics, 0.573 and 0.627, respectively). The Youden-optimal diagnostic cut-offs for the SICCA corneal and conjunctival staining scores were both ≥1, and the optimal thresholds for the Korb superior and inferior LWE grades were both ≥1. LWE was more commonly detected in both mild-to-moderate and moderate-to-severe dry eye disease, and demonstrated more consistent correlation with other ocular surface parameters across a broader range of disease severity. ConclusionsLWE demonstrates superior diagnostic performance relative to corneal and conjunctival staining. These findings would support the routine incorporation of LWE evaluation as part of the diagnostic workup of dry eye disease.

Comparing two mucin secretagogues for the treatment of dry eye disease: a prospective randomized crossover trial

This study aimed to compare the clinical efficacy and investigate patients’ preferences for two mucin secretagogues in the treatment of dry eye disease (DED). Thirty patients with DED were randomly treated with either 3% diquafosol or 2% rebamipide ophthalmic solution for 4 weeks, followed by an additional 4-week treatment using the other eye drop after a 2-week washout period. Objective and subjective assessments, including the corneal and conjunctival staining score, tear breakup time (TBUT), Schirmer 1 test, tear osmolarity, tear matrix metalloproteinase-9 (MMP-9), lipid layer thickness (LLT) and ocular surface disease index (OSDI), were performed at baseline, 4 weeks, 6 weeks, and 10 weeks. Patient preferences were assessed based on four categories (comfort, efficacy, convenience, willingness to continue) using a questionnaire and the overall subjective satisfaction score for each drug was obtained at the end of the trial. In total, 28 eyes from 28 patients were included in the analysis. Both diquafosol and rebamipide significantly improved the OSDI (p = 0.033 and 0.034, respectively), TBUT (p < 0.001 and 0.026, respectively), and corneal (p < 0.001 and 0.001, respectively) and conjunctival (p = 0.017 and 0.042, respectively) staining after 4 weeks of treatment. An increase in Schirmer test scores was observed only after rebamipide treatment (p = 0.007). No significant changes were detected in tear osmolarity, MMP-9, and LLT following both treatments. The patients’ preference was slightly greater for diquafosol (46.4%) than rebamipide (36.7%), presumably due to rebamipide's bitter taste. The self-efficacy of both drugs and overall satisfaction scores were comparable. These findings indicate that two mucin secretagogues showed comparable effects in ameliorating symptoms and improving signs (TBUT, corneal and conjunctival staining) in patients with DED.

Two-Year Progression of Dry Eye Disease in Dry Eye Assessment and Management Study.

The purpose of this study was to evaluate the progression of dry eye disease (DED) symptoms and signs over 2 years through a secondary analysis of data collected from the Dry Eye Assessment and Management study. Participants who were assigned to omega-3 fatty acid in the first year were rerandomized in the second year to either continue with omega-3 fatty acid or switch to placebo. At baseline, 3, 6, 12, 18, and 24 months, DED symptoms were evaluated by using the Ocular Surface Disease Index and the Brief Ocular Discomfort Index (BODI). DED signs were assessed using conjunctival staining, corneal staining, tear break-up time, Schirmer testing, and keratography measures. Medication usage was documented at each visit. Because the treatment and placebo groups displayed no statistical differences in both signs and symptoms, data from the 43 participants were combined to assess longitudinal changes in symptoms and signs. At 3 months after omega-3 fatty acid treatment, there were significant improvements from baseline in Ocular Surface Disease Index and Brief Ocular Discomfort Index scores (all P ≤ 0.002) and less use of artificial tears or gel ( P = 0.02), but between 3 and 24 months, no significant changes in symptoms and treatments were observed ( P ≥ 0.06). Except for a significant improvement in conjunctival staining score over 2 years ( P = 0.001), there were no significant sign changes in corneal staining ( P = 0.32), tear break-up time ( P = 0.43), Schirmer test ( P = 0.09), and additional measures (all P ≥ 0.07). We did not observe a progression of DED signs or symptoms over a 2-year period, except for a probable placebo response in symptoms in the first 3 months and an improvement in conjunctival staining score.

The Effect of Autografts from the Inferior and Superior Bulbar Conjunctiva on the Ocular Surface in Primary Pterygium Surgery: A Cytology Study.

This study aimed to evaluate the effect of using an inferior or superior conjunctival autograft in primary pterygium surgery on the postoperative ocular surface. Forty eyes of 40 patients who underwent pterygium surgery with autograft were included in the study. Cytological cell counts were performed on samples taken from the bulbar conjunctiva by impression cytology before and 1 year after the operation. Schirmer 1 test score, lissamine green conjunctival staining score, tear film break-up time (TBUT), and fluorescein corneal staining scores were evaluated. The pain levels of the patients were evaluated with visual analog scale at postoperative 1 day and 1 week. Corneal and conjunctival staining, TBUT, and Schirmer test results demonstrated significant improvement in all patient groups after surgery, but there was no difference between groups (p>0.05). In both preoperative and postoperative impression cytology, the number of goblet cells in the inferior bulbar conjunctiva was higher than in the superior bulbar conjunctiva (p<0.001), while there was no such difference in epithelial cell or mucin staining. There were no significant cytological changes postoperatively in either group (p>0.05). Pterygium surgery with autografting improved tear function tests regardless of graft location. Goblet cell count was higher in the inferior bulbar conjunctiva than in the superior bulbar conjunctiva in both postoperative and preoperative impression cytology. However, there was no significant difference in postoperative epithelial and goblet cell counts or mucin staining between the groups before and after surgery. We think that using the inferior bulbar conjunctiva is an appropriate choice in cases where the superior conjunctiva cannot be used as a graft or when future glaucoma surgery is possible.

Comparison of the Effects of 0.05% and 0.1% Cyclosporine for Dry Eye Syndrome Patients after Cataract Surgery

Purpose: We compared the effects of 0.05% and 0.1% cyclosporine on dry eye symptoms following cataract surgery.Methods: We retrospectively reviewed the medical records of patients with dry eye syndrome who underwent cataract surgery. The patients were separated into 0.05% and 0.1% cyclosporine groups. Each group had been treated with their routine eye drops for 3 months after cataract surgery. We evaluated dry eye symptoms and signs using the Schirmer test, tear film breakup time (TBUT), corneal and conjunctival staining score, ocular surface disease index (OSDI), and matrix metalloproteinase 9 (MMP-9) testing of the tear film preoperatively and at 2 weeks, 1 month, and 3 months postoperatively. We also compared dry eye symptoms between the groups by dividing all patients according to dry eye severity.Results: The study included 84 eyes (84 patients). The 0.05% cyclosporine group had an increase in the Schirmer test and improved corneal and conjunctival staining scores at 3 months postoperatively. The 0.1% cyclosporine group had improved corneal and conjunctival staining scores at 1 and 3 months postoperatively. The OSDI and MMP-9 results indicated a significant decrease in both groups at 2 weeks, 1 month and 3 months postoperatively. There were no significant differences in the change in dry eye symptoms after cataract surgery between the 0.05% and 0.1% cyclosporine groups. In the patients with level II dry eye syndrome, the 0.05% cyclosporine group showed a significant increase in the Schirmer test compared to the 0.1% cyclosporine group at 3 months postoperatively. The 0.1% cyclosporine group showed a significant improvement in TBUT compared to the 0.05% cyclosporine group at 3 months postoperatively.Conclusions: Both 0.05% and 0.1% cyclosporine are effective treatments for improving dry eye symptoms and ocular surface inflammation after cataract surgery. Both eye drops are considered to have similar effectiveness.

Efficacy and safety of platelet-rich plasma and autologous-serum eye drops for dry eye in primary Sjögren’s syndrome: a randomized trial

We compared the efficacy and safety of autologous-serum (AS) and platelet-rich plasma (PRP) eye drops for dry eye (DE) treatment in primary Sjögren’s syndrome (SS). This prospective, randomized, double-blinded clinical study included patients diagnosed with primary SS DE. Thirty-eight participants were randomly assigned to the AS or PRP groups. Corneal and conjunctival staining scores, Schirmer I test, tear film break-up time (TBUT), and ocular surface disease index (OSDI) scores were evaluated at 4 and 12 weeks. Conjunctival impression cytology (CIC) metaplasia grade and goblet cell density grade at 12 weeks were compared with those at baseline. Corneal and conjunctival staining scores and TBUT significantly improved at 4 and 12 weeks in both groups (all p < 0.005). No significant difference between the AS and PRP groups was observed at 4 and 12 weeks. The Schirmer I values, OSDI scores, CIC metaplasia grade, and goblet cell density grade did not significantly change at 4 and 12 weeks in either group. Both AS and PRP eye drops are effective for primary SS DE without a significant difference. Considering that the preparation time of PRP is shorter than that of AS, PRP can be a good alternative treatment for primary SS DE.

Association of Tear Cytokine Ratios with Symptoms and Signs of Dry Eye Disease: Biomarker Data from the Dry Eye Assessment and Management Study

Purpose To assess the relationship between tear inflammatory cytokine ratios (CRs) and signs and symptoms of dry eye disease (DED) to investigate the possible use of tear CRs, which may better address the complexity of cytokine interactions than absolute cytokine levels, as a DED biomarker. Methods Tear concentrations of IL-1b, IL-6, IL-8, IL-10, IL-17A, IFN-g, and TNF-a were measured using standardized procedures, as were DED signs (corneal and conjunctival staining scores, tear break-up time, Schirmer test, Meibomian gland plugging, tear osmolarity, composite sign severity score) and symptoms [Ocular Surface Disease Index (OSDI)]. Ratios between pro-inflammatory (IL-1b, IL-8, IL-17A, IFN-g, and TNF-a) and anti-inflammatory (IL-10) cytokines were calculated. Given its opposing roles in inflammation, IL-6 was tested as both a pro- and anti-inflammatory cytokine. Correlations between CR and DED symptoms and signs were calculated using Spearman correlation coefficients (rho). Results At baseline, 131 patients, 80.2% female and mean age 54.2 years (SD 14.1, range 20–82), from 10 sites of the Dry Eye Assessment and Management study had sufficient tear volumes ≥4 μL for analysis. IL-6:IL-10, IL-8:IL-10, and TNF-a:IL-10 had some significant correlations, mostly with conjunctival or corneal staining or the composite sign severity score (IL-8:IL-10 and conjunctival staining: rho = 0.19, p = 0.03; IL-6:IL-10 and corneal staining: rho = 0.31, p < 0.001; IL-8:IL-10 and corneal staining: rho = 0.21, p = 0.01; IL-6:IL-10 and composite sign severity score: rho = 0.26, p = 0.003; IL-8:IL-10 and composite sign severity score: rho = 0.26, p = 0.003; TNF-a:IL-10 and corneal staining: rho = 0.29, p < 0.001; TNF-a:IL-10 and Schirmer test: rho = −0.23, p = 0.009). CRs had no significant correlation with DED symptoms. All significant correlations using IL-6 in the denominator (anti-inflammatory) produced counterintuitive results based on clinical understanding of the disease. Conclusions Pro- to anti-inflammatory CR was weakly correlated with some DED signs and not with symptoms, as measured by OSDI. Future studies in different dry eye populations are needed and should address sampling biases and tear collection techniques.

Association of Dry Eye Symptoms and Signs in Patients with Dry Eye Disease

ABSTRACT Purpose To determine the correlations among symptoms and signs of dry eye disease (DED) in the Dry Eye Assessment and Management (DREAM) study. Methods A total of 535 patients with moderate-to-severe DED were assessed for symptoms using the Ocular Surface Disease Index (OSDI) and four DED signs in both eyes (conjunctival lissamine green staining, corneal fluorescein staining, Schirmer’s testing, and tear break-up time (TBUT)) following standardized protocols at baseline and follow-up visits (months 3, 6, and 12). Spearman correlation coefficients (rho) were calculated for correlations among symptoms and signs of DED at baseline and among changes in symptoms and signs from baseline at 12 months. The confidence intervals and p-values for correlation coefficients were calculated using a cluster bootstrapping to account for inter-eye correlation. Results At baseline, OSDI total score was not correlated with signs; however, OSDI subscale score of ocular symptoms was weakly correlated with corneal staining score (rho = 0.14, p = .002) and Schirmer test score (rho = 0.11, p = .01). There were statistically significant correlations among the four signs (p < .001), with absolute correlation coefficient ranging from 0.14 (conjunctival staining score vs. TBUT) to 0.33 (conjunctival staining score vs. cornea staining score). The correlations among changes in symptoms and signs were weaker, with the highest correlation between change in conjunctival staining and corneal staining (rho = 0.21, p < .001). Conclusions Consistent with previous studies, among DREAM participants with moderate-to-severe DED at baseline, correlations of DED symptoms with signs were low and correlations among four objective signs were low to moderate. The correlations among changes in symptoms and signs were even weaker.

Efficacy and safety of 1% and 2% rebamipide clear solution in dry eye disease: a multicenter randomized trial

BackgroundTo evaluate the efficacy of 1% and 2% rebamipide clear solution in the treatment of dry eye disease (DED).MethodsTwo hundred twenty patients with DED were randomly assigned to one of three groups: the 1% rebamipide, 2% rebamipide, or placebo (eye drops containing the same ingredients, except for the active components). Each eye drop was instilled four times daily for 12 weeks. Changes in tear film break-up time (TBUT), corneal and conjunctival staining score, Schirmer 1 test, and the Ocular Surface Disease Index (OSDI) from baseline to 12-week visit between the study groups were compared for efficacy assessment.ResultsThe mean age of study patients was 43.8±14.2 years. The 1% and 2% rebamipide groups showed greater improvement in TBUT (1.99±1.87 and 2.02±2.21 s) at 12 weeks from baseline than the placebo group (1.25±2.93 s). The 2% rebamipide group showed greater improvement in the corneal staining score (− 3.15±2.00) at 12 weeks from baseline than the placebo group (− 2.85±1.80). The 1% and 2% rebamipide groups showed improvement in Schirmer 1 test (1.27±3.86 and 1.50±4.14 mm) at 12 weeks of treatment, but not the placebo group (0.55±2.99 mm). Both the rebamipide groups and the placebo group showed significantly improved OSDI after treatment for 12 weeks; however, there was no significant difference among the three groups.Conclusions1% and 2% rebamipide clear solutions are an effective therapeutic option for improving TBUT and tear volume, and stabilizing the corneal staining score in DED.

Topical Spironolactone in the Treatment of Evaporative Dry Eye Disease.

Meibomian gland dysfunction (MGD) is associated with evaporative dry eye syndrome, which is characterized by a reduction in meibum secretion and tear film instability. Present treatments provide only temporary relief, thereby necessitating the exploration of novel therapeutic strategies for chronic treatment. This study aims to evaluate topical spironolactone, a medication with anti-mineralocorticoid, anti-androgenic, and anti-inflammatory properties, in treating dry eye. A retrospective observational study was performed on the medical records of 102 patients diagnosed with dry eye disease. These patients were categorized into two groups based on their Schirmer's tear test scores. Various clinical indicators, including subjective global assessment scores, visual acuity, keratitis, conjunctival staining scores, and lid margin health, were evaluated prior to and following treatment with topical spironolactone eye drops. The group with higher Schirmer's scores exhibited improvement in self-reported global assessment scores after treatment. Significant improvements were also observed in keratitis and conjunctival staining scores, visual acuity, and lid margin inflammation. Similarly, the group with lower Schirmer's scores demonstrated improvements in self-reported global assessment scores and visual acuity after treatment. Topical spironolactone may improve tear film quality and address the inflammatory processes associated with MGD and evaporative dry eye. Moreover, the topical administration of spironolactone in an ocular vehicle appears to be well tolerated and may mitigate the risk of systemic adverse effects. Further studies are warranted to explore the long-term effects of topical spironolactone in the treatment of evaporative dry eye disease.

Transcutaneous Electrical Stimulation for the Prevention of Dry Eye Disease after Photorefractive Keratectomy: Randomized Controlled Trial.

To evaluate the efficacy and safety of transcutaneous electrical stimulation (TES) for the prevention of dry eye after photorefractive keratectomy (PRK). Prospective, single-center, single-blinded, parallel group, placebo-controlled, randomized clinical trial. Between February 2020 and October 2020, patients at the Samsung Medical Center scheduled to undergo PRK to correct myopia were screened and enrolled. The participants in the TES group were instructed to use the electrical stimulation device (Nu Eyne 01, Nu Eyne Co) at the periocular region after the operation, whereas those in the control group were to use the sham device. Dry eye symptoms were evaluated preoperatively and postoperatively at weeks 1, 4, and 12 using the Ocular Surface Disease Index (OSDI) questionnaire, the 5-Item Dry Eye Questionnaire (DEQ-5), and the Standard Patient Evaluation for Eye Dryness II (SPEED II) questionnaire. Dry eye signs were assessed using tear break-up time (TBUT), total corneal fluorescein staining (tCFS), and total conjunctival staining score according to the National Eye Institute/Industry scale. The pain intensity was evaluated using a visual analog scale. Primary outcomes were OSDI and TBUT. Twenty-four patients were enrolled and completed follow-up until the end of the study (12 patients in the TES group, 12 patients in the control group). Refractive outcomes and visual acuity were not different between the groups. No serious adverse event was reported with regard to device use. No significant difference in OSDI and SPEED II questionnaires and the DEQ-5 was observed between the groups in the 12th week after surgery. The TBUT scores 12 weeks after the surgery were 9.28 ± 6.90 seconds in the TES group and 5.98 ± 2.55 seconds in the control group with significant difference (P= 0.042). The tCFS and total conjunctival staining score were significantly lower in the TES group than in the control group at postoperative 4 weeks. Pain intensity at the first week was significantly lower in the TES group than in the control group by 65% (P= 0.011). The application of TES is safe and effective in improving dry eye disease after PRK. The author(s) have no proprietary or commercial interest in any materials discussed in this article.