Long-Term Efficacy and Safety of 0.1% Cyclosporine A Cationic Emulsion in Advanced Dry Eye Disease: A 24-Month Retrospective Study

Understanding the Dual Dilemma of Dry Eye and Glaucoma: An International Review.

To compare the ocular surface disease index (OSDI) questionnaire with objective tests in dry eye disease. A prospective observational study. Place and Duration of the Study: Department of Ophthalmology, Nigde Omer Halisdemir University, Nigde, Turkiye, from 9th June to 31st December 2022. All clinically diagnosed 323 eyes of patients with dry eye disease (DED) were included. The subjects were evaluated by the Oxford classification of corneal and conjunctival fluorescein staining, Schirmer I test, and fluorescein tear breakup time (TBUT). Symptoms of the patients were interpreted with OSDI and correlations of symptoms and objective markers were analysed. There was no significant association between any objective signs (Schirmer I, TBUT, and Oxford), and OSDI (p = 0.26, 0.52, 0.18, and respectively). Schirmer I score showed a significant positive correlation with TBUT (p <0.001, r = 0.21) and a significant negative correlation with Oxford scale (p <0.001, r = -0.19). There was a statistically negative correlation between TBUT and Oxford scale (p <0.001, r = -0.37). Except for the Schirmer test, TBUT and Oxford scale are effective tools in the diagnosis of DED. Symptom markers, such as OSDI may have lower reliability in diagnosing DED and determining its severity. Diagnostic tests are important in the detection of asymptomatic or less severe dry eye disease that can be ignored. Dry eye disease, Diagnosis, Ocular surface disease index (OSDI), Tear breakup time (TBUT), Oxford grading scale, Schirmer I test.

Dry eye is a multifactorial ocular surface disorder. While artificial tears and anti-inflammatory medications are standard treatment, blood derivatives such as platelet-rich plasma (PRP) offer regenerative benefits as well and are gaining popularity in ophthalmology. This study aimed at the comparative evaluation of the clinical outcomes of autologous PRP eye dropand artificial tear eye drop (AT) therapy in the treatment of chronic evaporative dry eye patients with moderate to severe symptoms. 100 patients with chronic (≥ 6 months duration) evaporative moderate to severe dry eye disease (DED) in the 18 years to 45 years age group were included in this prospective interventional study. We randomized patients into two equal groups (n = 50 each). One group received autologous PRP eye drops and the other AT drops. The outcome measures evaluated were subjective symptoms (ocular surface disease index (OSDI) score), objective tear film parameters (Oxford corneal fluorescence staining (CFS) score, tear breakup time (TBUT), and Schirmer's test (ST) score),and best-corrected visual acuity (BCVA) (converted to LogMAR, with improvement defined as a gain of ≥ 1 Snellen line). Within the group and between the group, comparisons were done at the end of 6 months using paired and unpaired student's t-tests, respectively. At the end of 6 months, both the treatment groups (PRP and AT) showed significant improvement in OSDI and CFS scores, whereas TBUT and BCVA improved significantly only in the PRP group. No significant changes were observed in ST in either group. The post-treatment, between-the-groups analysis also favored PRP in all the parameters except ST. The PRP group showed significantly better improvements than the AT group in OSDI (MD, i.e., mean difference= -20.9,t= -5.12,P< 0.0001), CFS score (MD = -0.83,t= -5.08,P< 0.0001), TBUT (MD = 1.28,t= 3.08,P= 0.003), and BCVA (MD = -0.025,t= -2.15,P= 0.034). No significant difference was found in ST (P= 0.4). No significant adverse effect was noted throughout the study. In chronic evaporative DED patients,autologous PRP showed significantly better clinical outcomes than AT and was found to be safe when given for a 6-month duration.

To describe dry eye disease in French elderly subjects. The Alienor Study is a population-based study on age-related eye disease in 963 residents of Bordeaux (France), aged 73 years or more. Self-reported dry eye disease and use of artificial tears were documented through face-to-face interview. Dry eye symptoms were assessed using the Ocular Surface Disease Index (OSDI) questionnaire and tear film stability by tear break-up time measurements (TBUT). Definite dry eye disease was defined as self-reported dry eye, confirmed by use of artificial tears and/or OSDI greater or equal to 22. Nine hundred and fifteen subjects, with mean age of 80 ± 4 years, returned the OSDI questionnaire. Of these, 271 (29.6%) subjects reported a dry eye disease and 135 (14.7%) were using artificial tears. An OSDI score > 22 was found in 359 (39.2%) subjects and a TBUT < 5 seconds in 335/746 (44.9%) subjects. Overall, definite dry eye affected 21.9% of subjects and was more frequent in women (27.1%) than in men (13.6%). After multivariate adjustment, dry eye disease was also significantly less frequent in subjects with high educational level (odds ratio (OR) = 0.49, 95% confidence interval (CI): 0.31-0.78 for long secondary school) and more frequent in subjects with ocular hypertension (OR = 1.61, 95% CI: 1.02-2.57) and those using anxiolytics (OR = 1.53, 95% CI: 1.02-2.29). This large observational study confirmed the high prevalence of dry eye symptoms among elderly subjects and confirmed some of the previously identified risk factors (in particular female gender and use of anxiolytics).

Background: Dry eye disease (DED) is a multifactorial condition with a globally rising prevalence. Diagnosis relies on both symptoms and clinical tests, but these methods demonstrate variability. Strip meniscometry (SMTube) represents a rapid, non-invasive alternative method, but its diagnostic value remains uncertain. We evaluated the correlation of its findings with those of established DED evaluations. Methods: In this cross-sectional study, we recruited 100 individuals with and without DED (n = 50 each) who visited a tertiary ophthalmology clinic. Diagnosis of DED was based on symptomatology and standard criteria, including a tear break-up time (TBUT) &lt; 5 s or Schirmer test I result &lt; 5 mm, along with an Ocular Surface Disease Index (OSDI) score &gt; 12 and corneal fluorescein staining grade &gt; 1. The exclusion criteria included ocular surgery, allergy, or contact lens use. All participants underwent comprehensive ophthalmic examination and standardized DED assessments (OSDI, tear meniscus height [TMH], SMTube, TBUT, corneal fluorescein staining, and Schirmer test I), conducted in a controlled setting by a single examiner during 9–11 AM to ensure consistency. Results: The DED group was significantly older (P &lt; 0.05). No significant sex difference was observed between groups (P &gt; 0.05). The OSDI, TMH, SMTube, TBUT, corneal fluorescein staining, and Schirmer test I findings differed significantly (all P &lt; 0.001), while SMTube application discomfort rates were similar between groups (P &gt; 0.05). In the DED group, SMTube correlated moderately with TBUT (r = + 0.41, P &lt; 0.05) and OSDI (r = + 0.43, P &lt; 0.05), while the Schirmer test I correlated weakly with TBUT (r = + 0.34, P &lt; 0.05) and moderately with TMH (r = + 0.52, P &lt; 0.05). In the controls, no significant correlations were observed between tear metrics and SMTube or Schirmer test I findings (all P &gt; 0.05), except for corneal fluorescein staining, which showed a weak negative correlation with SMTube (r = - 0.28, P &lt; 0.05) and a moderate positive correlation with Schirmer test I findings (r = + 0.51, P &lt; 0.05). Conclusions: SMTube findings differed significantly between the DED and control groups and correlated moderately with those of established diagnostic assessments, particularly the TBUT and OSDI. Unlike Schirmer testing, SMTube results are closely associated with symptom severity, suggesting its utility in reflecting patient-reported discomfort. Given its simplicity, non-invasiveness, and correlation with key clinical indicators, SMTube may serve as a valuable adjunct in the multimodal assessment of DED. However, further studies are needed to establish its diagnostic accuracy and to confirm its clinical utility.

Objective: To assess the efficacy of 0.1% cyclosporine A (CsA) cationic emulsion (CE) in the treatment of dry eye disease (DED) in terms of ocular surface disease index (OSDI). Methods: DED patients with corneal fluorescein staining grade (CFS) ≤ 3 on the Oxford scale and Schirmer test score < 10 mm/ 5 min were enrolled for once-daily CsA use in this observational, prospective, one-center study. Efficacy of CE at 30, 60, and 90-day follow-up visit was evaluated using OSDI questionnaire. Both the overall OSDI score and the outcomes for all subscales - ocular symptoms (OS), vision-related function (VRF) and environmental triggers (ET) were considered.Results: Twelve patients (10 women and 2 men), whose baseline OSDI ranged between 27.08 and 70.03 mm (48.2 ± 11.8), were included. Their achieved mean scores for subscales such OS, VRF and ET were 66.6 ± 16.8, 42.2 ± 12.0 and 42.2 ± 12.5, respectively. Statistically significant results were obtained after 30 days for OSDI (45.5 ± 10.0; p=0.011), whereas after 90 days for both OSDI (35.4 ± 7.4; p=0.003) and OS (47.2 ± 10.9; p=0.005), VRF (30.5 ± 6.1; p=0.003) and ET (33.3 ± 11.2; p=0.008).Conclusions: CsA CE significantly reduced symptoms of patients with DED. Recovery was the most successful after 90 days of treatment and included OSDI, OS, VRF and ET.Abbreviations: CE = cationic emulsion, CFS = corneal fluorescein staining, CsA = cyclosporine A, DED = dry eye disease, ET = environmental triggers, OS = ocular symptoms, OSDI = ocular surface disease index, VRF = vision-related function

The aim of this study was to evaluate the role of topical human IgG eye drops (4 mg/mL) as adjunct therapy in eyes with moderate to severe refractory dry eye disease (DED). A prospective, longitudinal, open label, dual cohort study of patients with chronic DED of moderate to severe grade comprise of OSIG therapy group cohort on topical immunoglobulin IgG 0.4% four times daily, as adjunctive therapy for one year, to study the role of OSIG therapy in comparison with conventional treatment. Patients above 18 years of age with chronic moderate to severe grade DED with tear break-up time (TBUT) ≤7 seconds, Schirmer test ≤9 mm/5 minutes, ocular surface disease index (OSDI) score ≥13, National Eye Institute (NEI) corneal staining score >3, and conjunctival staining score >3 were recruited into the study. Study participants in the conventional treatment cohort group were on topical lubricants four hourly (carboxymethyl cellulose 0.5% and lubricant ointment at bedtime), topical steroids (prednisolone 1%/fluorometholone 0.1%/loteprednol 0.5%) therapy as per the severity of the DED requirement and topical immunomodulators (cyclosporine A 0.1% eye drops or tacrolimus 0.1% eye ointment) twice daily. Study participants in the OSIG treatment cohort group were started on topical human immunoglobulin IgG 0.4% four times daily as adjunct therapy in addition to the all the above-mentioned medications for a period of 12 months. Study parameters included DED severity level assessment, NIH score, ocular surface evaluation tests, Schirmer's I test, TBUT, corneal and conjunctival staining score, OSDI score, and conjunctival hyperemia score. Ocular surface imaging using LipiView and ocular surface analyzer imaging for non-invasive TBUT (NITBUT), meibomian gland, and tear imaging was performed for the OSIG treatment cohort. Study characteristics were evaluated at time of recruitment into the study (baseline visit) and at serial follow-up of months 3, 6, and 12 in OSIG treatment group and follow-up at month 6 in conventional treatment group. Treatment grading score was devised in accordance to the frequency of application of lubricants and steroids and potency of steroids. Our study of 71 eyes of 36 patients [mean age 39 ± 11.80 years] in OSIG treatment cohort group and 64 eyes of 32 patients [mean age 40 ± 11.53 years] in conventional treatment cohort group observed a significant reduction in the objective ocular surface symptom assessment parameters of OSDI scores, and dry eye severity level with improvement in clinical assessment parameters of TBUT, ocular surface staining scores, and conjunctival hyperemia grades in eyes on adjunct OSIG treatment cohort as compared to the conventional therapy cohort. The frequency of topical lubricants and steroids along with the potency of steroids used showed a decreasing trend with 45.28% noted to have become free of steroid dependence at the end of 12 months of OSIG therapy. Adjunct topical IgG therapy also enabled the shifting of 37.14% of eyes from higher to lower potency steroids by the end of 12 months of treatment with OSIG therapy. The frequency of administration of lubricants decreased in 83.33% of eyes 12 months follow-up. The success rate determined based on improvement in ocular surface evaluation was 75.76%, treatment scores improved in 74.98%, and symptoms evaluation (OSDI) was 75.76% in the OSIG therapy cohort. Topical immunoglobulin IgG 0.4% as adjunct therapy seems to have a definitive role in reducing topical steroid and lubricant dependency in moderate to severe chronic DED compared to conventional therapy.

BackgroundTo evaluate the therapeutic effect of intense pulsed light (IPL) therapy with optimal pulse technology (OPT) on meibomian gland dysfunction (MGD) with and without ocular Demodex infestation.MethodsThis prospective study included 150 patients with MGD who were divided into Demodex-infested (DI) and non-infested (control) groups according to Demodex counts determined by epilating eyelashes to evaluate. Each patient underwent three OPT treatment sessions at 3-week intervals. Best corrected visual acuity (BCVA), intraocular pressure (IOP), Demodex counts, Ocular Surface Disease Index (OSDI) score, conjunctival congestion, tear meniscus height (TMH), tear breakup time (TBUT), Schirmer I test (SIT), corneal and conjunctival fluorescein staining scores, meibomian gland (MG) macrostructure, lid margin abnormality, MG expressibility, and meibum quality were assessed before the first treatment as baseline and at 1, 2, and 3 months (M1, M2 and M3, respectively) after treatment.ResultsThe incidence of Demodex infestation was 59.15% (84/142) at baseline and the final Demodex eradication rate at M3 was 83.3% (70/84). Corneal staining and conjunctival congestion showed slower improvement in the DI group than in the control group at M1 and M2 (P<0.05), but was significantly improved at M3 than that at with baseline (P<0.01). Both the groups showed significant improvement in OSDI, conjunctival congestion, TBUT, corneal and conjunctival staining, MG dropout, lid margin abnormality, MG expressibility, and meibum quality at M3 (P<0.05). No differences were observed for BCVA, IOP, SIT, and TMH before and after treatment in both the groups (P>0.05).ConclusionsThis new-generation IPL with OPT treatment results in greater improvement in MG expressibility and meibum quality in MGD patients with Demodex infestation than in those without, but not for corneal staining.

This study aims to understand the effect of vitamin B12 deficiency on neuropathic ocular pain (NOP) and symptoms in patients with dry eye disease (DED). Patients with severe DED (without receiving topical artificial tears treatment) and ocular pain were enrolled (n = 90). Patients with severe DED and vitamin B12 deficiency (group 1, n = 45) received parenteral vitamin B12 supplement + topical treatment (artificial tears treatment + cyclosporine), and patients with severe DED and normal serum vitamin B12 level (group 2, n = 45) received only topical treatment (artificial tears treatment + cyclosporine). Patients were evaluated by the ocular surface disease index (OSDI) questionnaire, 3rd question (have you experienced painful or sore eyes during last week?) score of OSDI as a pain determiner and pain frequency measure), tear break up time (TBUT), and Schirmer's type 1 test. We compared the groups' OSDI, TBUT, and Schirmer's test recordings at the first visit and after 12 weeks retrospectively. The OSDI score, 3rd OSDI question score, TBUT, and Schirmer's test results improved after 12 weeks (p < 0.001 for each group). The mean vitamin B12 level at enrollment was 144.24 ±43.36 pg/ml in group 1 and 417.53 ±87.22 pg/ml in group 2. The mean vitamin B12 level in group 1 reached to 450 ±60.563 pg/ml after 12 weeks of treatment. The mean score changes between the groups were not statistically significant; however, the decrease in the OSDI questionnaire score (-30.80 ±5.24) and 3rd OSDI question score (-2.82 ±0.53) were remarkable in group 1 (Table 2). The mean TBUT increase was +7.98 ±2.90 s and Schirmer's test result increase was +12.16 ±2.01 mm in group 1. The mean TBUT increase was +6.18 ±1.49 s and Schirmer's test result increase was +6.71 ±1.47 mm in group 2. These findings indicate that vitamin B12 deficiency is related with NOP. It may be important to consider measuring the serum vitamin B12 level in patients with severe DED presenting with resistant ocular pain despite taking topical treatment.

Objective To compare the effects of intraoperative corneal wetting by Croma, balanced salt solution (BSS), and hydroxypropyl methylcellulose (HPMC) on xerophthalmia after cataract surgery. Methods This prospective study included 79 patients (90 eyes) who were randomly assigned to a Croma corneal wetting properties group, balanced salt solution (BSS) group, or domestic hydroxypropyl methylcellulose (HPMC) group. Croma is a ophthalmological product to protect corneal epithelium, whose main ingredients is 2%HPMC. The solutions were applied to the ocular surface during the surgery to keep it moist. The following were measure pre-operatively and at 1, 7, and 30 days after cataract surgery, and the effect of each solution was assessed: objective scatter index (OSI) and the amplitude of OSI (OSI-A), tear break-up time (BUT), corneal fluorescein staining (CFS), Schirmer I test (SIt), and the ocular surface disease index (OSDI) questionnaire scores. Data were analyzed by repeated ANOVA or Kruskal-Wallis test. Results There were significant differences for OSI and SIt among the three groups (P<0.05). For OSI and SIt, the Croma group had significantly better results than the BSS group at post-operative days 1, 7, and 30 (all P<0.05). The Croma group had significantly higher SIt scores for tear secretion than the HPMC group at 7 and 30 days after surgery (P<0.05). Similar changes in trends were discovered with repeated measures analysis. BUT of the three groups all declined and revealed a significant difference among the pre- and post-operative (P<0.05). For the BSS group, several of the measured parameters were worse than the pre-operative values. On post-surgical day 1, SIt and OSI-A were worse (P<0.05 each), subjective complaints were worse on day 7 (P<0.05), and CFS was worse on day 30 (P<0.001). In the HPMC group, SIt and OSI-A increased significantly on post-operative day 1 (P<0.05). In the Croma group, and there was a slight increase in OSI-A and SIt at the same time. Neither CFS nor OSDI scores increased for either the HPMC or the Croma groups. Conclusion Both Croma corneal wetting properties and domestic HPMC were more beneficial than BSS for alleviating xerophthalmia after cataract surgery. The reduction of tear secretion and the increase in corneal epithelial staining were smaller in the Croma group than in the HPMC and BSS groups, and patients had less discomfort. Therefore, the Croma corneal wetting properties were significantly better than the others. Key words: Cataract extraction; Xerophthalmia; Corneal wetting properties; Stability of tear film; Tear secretion

To evaluate the effectiveness of conventional therapy and 20% autologous platelet-rich plasma (aPRP) eye drops for moderate to severe dry eye disease (DED). In this prospective interventional study, 40 individuals (80 eyes) with moderate to severe DED were analyzed. Twenty patients each were randomly assigned to the study and control groups. The study group was given 20% aPRP eye drops; the control group was given artificial tears as per conventional treatment. Comprehensive eye examinations including evaluation of best corrected visual acuity (BCVA), tear meniscus height, tear break-up time (TBUT), Schirmer's test, corneal fluorescein staining, conjunctival impression cytology, and Ocular Surface Disease Index (OSDI) were conducted in both groups for 3 months. Pre- and posttreatment results were compared. The average age of patients in the study group was 51±14 years (range, 37-65 years), whereas that of the control group was 50±17 years (range, 33-67 years). After 3 months, there was a more significant decrease in OSDI score in the study group than in the control group (p<0.01). The BCVA data demonstrated no statistically significant difference (p>0.05). Measurements of tear meniscus height, Schirmer's value, and TBUT at 3 months showed statistically significant differences (p<0.01). The posttreatment improvements in fluorescein staining and impression cytology scores in the study group were markedly superior to those in the control group (p<0.01). aPRP is both safe and more effective than conventional treatments for moderate to severe symptomatic DED.

ObjectivesTo address the lack of nerve and blood supply after labial salivary gland transplantation (LSGT) resulting in glandular atrophy. We designed a modified LSGT, called insular infraorbital neurovascular pedicle LSGT,...

Purpose To evaluate the clinical efficacy of oral hyaluronic acid (HA) in patients with dry eye disease (DED). Study Design Prospective randomized controlled trial. Methods This trial enrolled 54 subjects and they were randomized into the study or control group. The inclusion criteria were as follows: (1) >18 years of age; (2) distance best-corrected visual acuity ≥ 20/40 Snellen equivalent in each eye; (3) IOP ≤ 21 mmHg in both eyes; (4) ocular surface disease index (OSDI) score of ≥18 and <65; (5) <10 seconds of tear break up time (TBUT); (6) >5 corneal spots of corneal fluorescein staining (CFS); and (7) ≤ 10 mm/5 min of the Schirmer test. All subjects were treated with a topical HA, and the study group was supplemented with oral HA. OSDI, TBUT, CFS, and the Schirmer test were evaluated for ocular surface parameters. Results 24 patients were assigned in the study group. Significant improvement of OSDI, TBUT, and CFS was observed at 1 month and 3 months after oral HA administration in the study group. At baseline and follow-up at 1 and 3 months, OSDI scores were 61.8 ± 16.2, 47.3 ± 11.6, and 42.3 ± 9.1, respectively (P < 0.001). TBUT was improved after treatment for 1 month and 3 months (4.2 ± 1.1; P=0.005 and 4.7 ± 1.1; P < 0.012). There were also statistically significant improvements in the CSF (1.8 ± 1.0, 0.8 ± 0.7; P < 0.001) at baseline compared with those at 1 month. Conclusions A combined supplement of both oral and topical HA more efficiently improves corneal epithelial wound healing and related symptoms than topical HA alone, in DED.

This study aimed to evaluate the relationship between the objective severity of dry eye disease subjective symptoms, and corneal sensitivity. The study included 62 eyes from 31 healthy volunteers and 150 eyes from 75 patients diagnosed with dry eye disease . Participants underwent the Schirmer I test, tear break-up time assessment, and corneal staining evaluation using the Oxford Scale. Subjective symptoms were assessed through the Ocular Surface Disease Index questionnaire and a modified Ocular Surface Pain Score questionnaire. Corneal sensitivity was measured in five corneal regions using a Cochet-Bonnet esthesiometer. Dry eye disease severity was graded from 1 to 5 based on the Oxford Scale. Comparative analyses were performed. Schirmer I and tear break-up time values were significantly lower in the DED group, while Ocular Surface Disease Index and Ocular Surface Pain Score were significantly higher (p<0.001 for all). Corneal sensitivity in all quadrants was significantly lower in DED patients (p<0.001 for all). A strong correlation was observed between the Ocular Surface Pain Score and the Ocular Surface Disease Index (r=0.983, p<0.001). Central corneal sensitivity exhibited a moderate positive correlation with Schirmer I and tear break-up time (p<0.001, r=0.583 and 0.657, respectively) and a moderate negative correlation with Ocular Surface Disease Index and Ocular Surface Pain Score (p<0.001, r=0.625 and -0.631, respectively). Disease severity progression was associated with increased Ocular Surface Disease Index and Ocular Surface Pain Score, but no statistically significant difference was found between Grades 3 and 5. Similarly, corneal sensitivity decreased with advancing disease severity, yet no significant difference was observed between Grades 4 and 5. Corneal sensitivity decreases in dry eye disease and is negatively correlated with disease severity. Subjective symptoms increase with disease progression and show a positive correlation with severity. The absence of significant differences between the advanced stages suggests that neuropathic mechanisms and subbasal nerve plexus deterioration play a role in chronic and late-stage dry eye disease.

PURPOSE:To evaluate the efficacy and safety of 0.1% cyclosporine A cationic emulsion (CsA CE) following prior treatment with 0.05% cyclosporine A anionic emulsion (CsA AE) in moderate to severe dry eye disease (DED).MATERIALS AND METHODS:We retrospectively identified patients with moderate-to-severe DED who had shown an inadequate response to twice-daily use of topical 0.05% CsA AE but showed a significant improvement after switching to 0.1% CsA CE daily. Dry eye parameters before and after CsA CE were evaluated by tear break-up time (TBUT), corneal fluorescein staining (CFS), cornea sensitivity, Schirmer's test without anesthetics, and Ocular Surface Disease Index questionnaire.RESULTS:Twenty-three patients, including ten patients with Sjogren syndrome and five patients with rheumatoid arthritis, were reviewed. After a 2-month course of treatment with topical 0.1% CsA CE, significant improvements were noted for CFS (P < 0.001), corneal sensitivity (P = 0.008), and TBUT (P = 0.01). Efficacy was similar in the autoimmune versus nonautoimmune group. 39.1% of patients reported treatment-related adverse events, while the majority was transient instillation pain. Visual acuity and intraocular pressure had no significant changes during the study.CONCLUSION:In patients with moderate to severe DED refractory to 0.05% cyclosporine, shifting to 0.1% cyclosporine showed improvement in objective signs but with lower treatment tolerability in the short term.