Conjunctival Lissamine Green Staining Research Articles

Prevalence and Risk Factors of Dry Eye Disease in the South of Palestine.

The prevalence of dry eye disease (DED) is rising globally and needs to be urgently addressed by medical professionals because it lowers patients' quality of life. There are as yet no available data in the literature about the prevalence of and risk factors for DED in the Gaza Strip, a gap that the present study seeks to address. A cross-sectional study was carried out between March and August 2022 in Gaza governorates using a proportional stratified sampling technique. Only Gazan individuals ≥ 18 years old and able to follow the instructions were included. The Ocular Surface Disease Index (OSDI) questionnaire, which has previously been translated into Arabic and validated, was applied to evaluate DED symptoms. Subjective clinical tests for DED conducted were tear meniscus height (TMH), meibomian gland dysfunctions (MGDs), Marx line (ML), conjunctival Lissamine green staining (LGS), tear film break-up time test (TBUT), corneal fluorescein staining (CFS) and Schirmer II tear test (STT). DED was defined based on an Arab-OSDI score ≥ 13 and at least one positive clinical sign. A total of 426 participants were assessed from four areas (North Gaza Strip, 82; Gaza City, 147; Mid-Zone Gaza Strip, 62; South Gaza Strip, 135). The prevalence of DED in the present study was 31.5% (95% CI: 27.1, 36.1). Age > 50 years old (odds ratio [OR] = 10.45; 95% CI: 2.95, 37.05; P < 0.001), female gender (OR = 3.24; 95% CI: 1.40, 7.52, P = 0.006), menopause or pregnancy (OR = 2.59; 95% CI: 1.25, 5.35; P = 0.03) and pharmacotherapy (artificial tears; OR = 9.91; 95% CI: 2.77, 35.46; P < 0.001) were each associated with DED symptoms. South Gaza Strip (OR = 0.04; 95% CI: 0.01, 0.12; P < 0.001), unemployed (OR = 11.67; 95% CI: 1.43, 95.44; P = 0.02), non-consumption of caffeine (OR = 0.40; 95% CI: 0.19, 0.88; P = 0.02) and TMH < 0.2 (OR = 1.80; 95% CI: 1.02, 3.19; P = 0.04) were associated with TBUT < 5 s. LGS was associated with those > 50 years old (OR = 2.70; 95% CI: 1.38, 5.28; P = 0.004), previous refractive or ocular surface surgeries (OR = 2.97; 95% CI: 1.34, 6.59; P = 0.008) and CFS ≥ 1 (OR = 1.91; 95% CI: 1.07, 3.44; P = 0.03). Various aspects of DED were linked with different risk factors, suggesting that DED subtypes have different underlying pathophysiologies.

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.

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.

Improving Visual Comfort during Computer Gaming with Preservative-Free Hyaluronic Acid Artificial Tears Added to Ergophthalmological Measures.

Digital asthenopia (DA) or Computer Vision Syndrome can occur after prolonged use of digital devices and is usually managed with ergophthalmological measures and the use of artificial tears. This prospective, controlled study evaluated the use of hyaluronic acid artificial tears on the signs and symptoms of DA in participants of a videogame convention. Subjects (n = 56) were randomized into a control group (CG, n = 26), which followed ergophthalmological measures, and a study group (SG, n = 30), which followed ergophthalmological measures and instilled 1 drop of artificial tears with hyaluronic acid 0.15% four times a day. Subjects were evaluated before and after playing for three consecutive days for eye dryness (SPEED questionnaire), conjunctival hyperemia, corneal fluorescein staining, conjunctival lissamine green staining, tear breakup time, Schirmer I test, near convergence and accommodation, and using questionnaires for DA symptoms. After 3 days of intense videogaming, the SPEED score of CG increased significantly (p = 0.0320), while for the SG it was unchanged. Similarly, the CG presented significant increases in ocular fatigue (p = 0.0173) and dryness (p = 0.0463), while these parameters decreased significantly in the SG (p = 0.0149 and p = 0.00427, respectively). This study confirms the protective effect of hyaluronic acid artificial tears against DA symptoms associated with prolonged visual display terminal use.

Effect of Autologous Platelet-Rich Plasma Drops in the Treatment of Ocular Surface Disease.

Platelet rich plasma (PRP) is an autologous preparation that concentrates platelets in a small volume of plasma. The purpose of this study was to determine if PRP eye drops improved the symptoms and signs of ocular surface disease. A retrospective case series was conducted of patients who were prescribed PRP eye drops. Subjects were excluded if they did not have follow-up, underwent intraocular surgery prior to follow-up, received nerve growth factor treatments, or did not have a baseline examination with photography. Symptoms were assessed using the Ocular Surface Disease Index (OSDI). Patients also underwent a slit lamp exam, ocular surface staining with fluorescein and lissamine green, and Schirmer testing. The charts of 47 patients treated with PRP drops for ocular surface disease were reviewed. Sixty-four eyes of 32 patients were included in the study who had photographs of lissamine green staining taken at baseline and at follow-up. Thirteen patients (28%) had ocular graft-versus-host disease, 16 patients (34%) had Sjögren's syndrome, and 4 patients (8.5%) had rheumatoid arthritis. There was a statistically significant decrease in OSDI score from baseline to follow-up (39.5 vs 30.8 points, p = 0.02). Among the 64 eyes included, 9 (14%) had an improvement in conjunctival lissamine green staining, while 6 (9%) had an increase in staining at follow-up. Among the 20 eyes with Schirmer testing, there was a borderline significant increase in score from baseline to follow-up (5.9 vs 9.7, p = 0.06). Among the 44 eyes that had corneal fluorescein staining (CFS) reported, 8 (18.2%) had decreased staining and 2 (4.5%) had increased staining at follow-up. Treatment with PRP drops was associated with a significant improvement in symptoms in patients with ocular surface disease. Future larger prospective studies are needed to further evaluate the efficacy of PRP drops for treating ocular surface disease.

Effect of Thermoelectric Warming Therapy for the Treatment of Meibomian Gland Dysfunction

To evaluate the efficacy of thermoelectric warming therapy (MiBoFlo) in improving patient symptoms with standardized questionnaires and objective signs of meibomian gland dysfunction (MGD), which is an important underlying treatable factor in dry eye disease (DED), such as ocular surface staining, tear quality, and meibomian gland morphology. Multivariate analysis to identify predictors for the improvement in Ocular Surface Disease Index (OSDI) was also performed. Retrospective before-and-after study. A total of 203 eyes of 102 patients with DED were treated with MiBoFlo at the dry eye center. The OSDI and Standard Patient Evaluation of Eye Dryness (SPEED) questionnaires, best-corrected visual acuity, tear osmolarity, tear film breakup time (TBUT), corneal and conjunctival staining, meibography, number of glands expressing liquid, and quality of the improved meibum were assessed before and 6 months after MiBoFlo. Exclusion criteria included active ocular inflammation. Dry eye symptoms improved in the population, with both SPEED and OSDI lowering of dry eye symptoms by approximately 35% (P < .001) at month 6. Significant improvements in lissamine green conjunctival staining, corneal fluorescein staining, TBUT, osmolarity, and secreting meibomian glands and meibum quality were also seen. Improvement was seen across all domains of the questionnaires and across all baseline parameters. Eyes with blepharitis and autoimmune disease improved less than average. No complications or adverse events occurred. MiBoFlo treatments produced clinical and statistically significant improvements in the signs and symptoms of MGD, irrespective of underlying ocular conditions. This improvement was sustained for the 6-month period of observation after initiating the treatment.

A Randomized Trial of Topical Fibrinogen-Depleted Human Platelet Lysate Treatment of Dry Eye Secondary to Chronic Graft-versus-Host Disease.

PurposeThe purpose of the study was to evaluate, as a pilot trial, safety and tolerability of CAM-101 10% and 30% topical ophthalmic fibrinogen-depleted human platelet lysate (FD hPL) solution in patients with dry eye disease (DED) secondary to graft-versus-host disease (GvHD) after 6 weeks of treatment.DesignA phase I/II, pilot, prospective, multicenter, randomized, double-masked clinical trial.ParticipantsPatients with DED secondary to GvHD.MethodsSixty-four adult patients were stratified by “symptom severity” (Ocular Surface Disease Index [OSDI], ocular discomfort Visual Analog Scale (VAS), ocular symptom frequency, and use of artificial tears) and then randomized 1:1:1 to CAM-101 (FD hPL) at 10% or 30% concentration or an electrolyte (Plasma-Lyte A) vehicle control, 1 drop in both eyes, 4 times daily, for 42 days. After 42 days, control patients were offered 42 days of open-label treatment with 30% FD hPL.Main Outcome MeasuresPrimary outcome safety measures were ocular and systemic adverse events and the number of patients in each group with clinically significant change from normal to abnormal in any ocular findings. Secondary outcomes were changes from baseline to day 42 in ocular discomfort, OSDI, fluorescein corneal staining, and lissamine green conjunctival staining relative to the vehicle control. The ocular symptom frequency was assessed on a 100-point VAS.ResultsFD hPL 10% and 30% were safe and well tolerated. Relative to the vehicle control, significant decreases from baseline to day 42 were seen in the FD hPL 30% group with regard to ocular discomfort (mean decrease = −18.04; P = 0.018), frequency of burning/stinging (−20.23; P = 0.022), eye discomfort (−32.97; P < 0.001), eye dryness (−21.61; P = 0.020), pain (−15.12; P = 0.044), photophobia (−24.33; P = 0.0125), and grittiness (−20.08; P = 0.0185). Decreases were also seen for itching and foreign body sensation, though not statistically significant. Improvements were seen in tear breakup time (mean increase = 1.30 seconds; P = 0.082) and the investigator’s global evaluation 4-point scale (mean decrease = −0.86; P = 0.026). Corneal fluorescein staining was not improved. The OSDI had a mean decrease of −8.88 compared to the vehicle, although not statistically significant.ConclusionsFibrinogen-depleted human platelet lysate appears to be well tolerated, with no significant toxicity at concentrations of 10% and 30%. These initial data suggest some efficacy, especially for subjective outcome measures relative to baseline assessments and treatment with the vehicle, but larger studies are needed to confirm these effects.

The effect of time on grading corneal fluorescein and conjunctival lissamine green staining

PurposeTo explore the effect of time on grading corneal fluorescein and conjunctival lissamine green staining in dry eye disease (DED). MethodsPhotographs of 68 subjects with non-Sjogren's DED (nSS DED) and 32 with Sjogren's DED (SS DED) were taken of corneal fluorescein staining, then conjunctival lissamine green staining every 30 s for at least 5 min. Photographs of one randomly selected eye were then randomly ordered and graded on a scale from 0 to 5 (severe staining) by two clinicians, masked to both site and subject. The average time required to reach the maximum grade of staining (Gmax) was calculated. ResultsThe median time (upper and lower quartiles) to corneal fluorescein Gmax was 2.6 (1.3–5.3) minutes for nSS DED and 3.8 (2.6–5.4) minutes for SS DED, a statistically significant difference (Mann Whitney U test, p = 0.018). In contrast, the median time to the Gmax for lissamine green staining of the nasal and temporal conjunctiva was 0.5 (0.5–1.1 nasal, 0.5–0.8 temporal) minutes for nSS DED and 0.5 (0.5–0.8 nasal, 0.5–0.5 temporal) minutes for SS DED subjects, which was not statistically significant (p ≥ 0.383). ConclusionsThe time required to reach the maximum grade of corneal fluorescein staining, but not conjunctival lissamine green staining, varied widely and was significantly longer in subjects with Sjögren's Syndrome. Early observation of corneal fluorescein staining can lead to under-grading, which may impact the diagnosis and assessment of treatment in DED. Further study of the best time to assess corneal fluorescein staining in various DED populations is warranted.

Results from a Prospective, Open-Label, Phase 4 Pilot Study of Repository Corticotropin Injection for Moderate and Severe Dry Eye Disease.

IntroductionThere is a substantial unmet need for effective therapies to treat patients with refractory dry eye disease (DED). The goal of this open-label pilot study was to investigate the efficacy and safety of repository corticotropin injection (RCI; Acthar® Gel; Mallinckrodt Pharmaceuticals) in subjects with DED, most of whom did not experience adequate response to standard-of-care therapies.MethodsAdults with moderate or severe-acute DED received 80 U of subcutaneous RCI twice weekly for 12 weeks. Primary efficacy outcomes were improvements in corneal fluorescein staining of superficial punctate keratitis (SPK) lesions and Symptom Assessment in Dry Eye (SANDE) scores. Secondary outcomes included changes in Schirmer’s test scores, conjunctival lissamine green staining, erythema, intraocular pressure (IOP), and best corrected visual acuity (BCVA). Adverse events (AEs) were assessed continuously throughout the study.ResultsFifteen subjects received at least 1 dose of RCI, and 12 subjects completed the study. Compared to baseline (day 1), significantly fewer fluorescein-stained SPK lesions were detected at day 14 (p = 0.0250) and day 84 (p = 0.0240) after RCI treatment. Mean SANDE scores progressively declined from 62.0 at baseline to 46.9 at day 84. Erythema (p = 0.0046), conjunctival lissamine green staining of SPK lesions (p = 0.0317), and IOP (p = 0.0052) were all significantly improved after 12 weeks of RCI therapy. Schirmer’s test scores and BCVA showed no significant changes throughout the study. No ocular AEs or deaths occurred, and no new safety signals were identified for RCI.ConclusionsThese results suggest that RCI may be a safe and effective treatment for moderate and severe DED.Trial registrationClinicalTrials.gov identifier: NCT03287635.

Effect of low-level light therapy in patients with dry eye: a prospective, randomized, observer-masked trial

To evaluate the efficacy of low-level light therapy (LLLT) with near-infrared light-emitting diodes (LED-LLLT) for the treatment of dry eye. 40 patients were randomly assigned with a 1:1 allocation ratio to receive LED-LLLT (LLLT group, n = 20) or placebo treatment (placebo group, n = 20). Patients in the LLLT group received LLLT twice a week for 3 weeks, for a total of 6 treatment sessions. The primary endpoint was the changes in the fluorescein corneal staining (FCS) score. The secondary endpoints were the changes in the ocular surface disease index (OSDI) score, lissamine green conjunctival staining (LGCS) scores, tear film break-up time (TBUT), Schirmer test, and the meibomian gland dysfunction (MGD) index. These were evaluated before treatment and 4 weeks after start of treatment. The mean difference of score change in primary endpoint revealed significant improvement in the LLLT group, compared to the placebo. Among secondary endpoints, LGCS, Schirmer's test, upper meibography scores showed significant improvements, while TBUT, lid debris, lid swelling, lid telangiectasia, meibomian gland secretion and expressibility scores had slight improvement without significant differences. No serious adverse events were observed. The use of LED-LLLT for the treatment of dry eye and MGD appears to be safe and beneficial.

Correlation between the presumed pterygium with dry eye and with systemic and ocular risk factors.

To estimate the epidemiology of the pterygium and its correlation with dry eye symptoms and with the potential systemic and ocular predictors. This study is a population-based, cross-sectional study in which random visits were made to the 600 households of 600 participants of age ≥40 years in Ribeirão Preto-SP (n=420) and Cassia dos Coqueiros-SP (n=180) in Brazil. The participants were subjected to a structured interview with a detailed questionnaire to collect information on demography and the potential risk factors. Next, random participants with pterygium (n=63) or not (n=110) were evaluated for the ocular surface changes. The frequency of pterygium in Ribeirão Preto was 21% (15.7% among women and 32.1% among men; p=0.0002). In Cássia dos Coqueiros, the corresponding frequency was 19.4% (17.3% among women and 25.5% among men; p=0.28). The mean age of the affected individuals was higher than that of the unaffected ones (65.6 ± 10.5 years vs. 61.2 ± 12.0 years, p=0.02). A positive correlation was noted between pterygium and any prior radiotherapy and chemotherapy (p<0.0001, for both). A higher score on corneal fluorescein and conjunctival lissamine green staining was asso ciated with pterygium (p=0.0003 and 0.0001, respectively). We noted a high frequency of pterygium in two Brazilian adult populations, mainly among the men and elderly. Ocular surface damage and a previous history of radiotherapy and/or chemotherapy were found to be associated with pterygium.

Clinical Analysis of Dry Eye Syndrome According to Anterior Displacement of the Marx Line

Purpose: To evaluate the clinical characteristics of patients with dry eye syndrome according to anterior displacement of the Marx line.Methods: This retrospective study involved 127 eyes in 127 patients with dry eye, who were divided into three groups: group 1, aqueous-deficient, including Sjögren syndrome; group 2, meibomian gland dysfunction (MGD) dry eye; and group 3, other tear layer instability. A detailed assessment was conducted, involving the Ocular Surface Disease Index, corneal fluorescein staining (score: 0-15), conjunctival Lissamine green staining (score: 0-12), measurement of tear breakup time, and Schirmer’s test.Results: The proportion of patients with MGD was highest in the group with anterior displacement of the Marx line (&lt;i&gt;p&lt;/i&gt; &lt; 0.05). The correlation between anterior dislocation of the Marx line and Schirmer’s test, an objective indicator of dry eye syndrome, was significantly weaker when there was anterior displacement of the Marx line.Conclusions: Anterior dislocation of the Marx line was more common in patients with MGD. The Marx line is a useful marker for diagnosing MGD.

Analysis of the Association between Galectin-3 Concentration in Tears and the Severity of Dry Eye Disease: A Case-Control Study.

This study aimed to investigate the relationship between the severity of dry eye disease (DED) and galectin-3 concentration (gal-3) and its cleavage (gal-3C) in tear fluid. Twenty-eight DED patients and 14 controls were recruited at Keio University Hospital. The lissamine green conjunctival staining (LG) score, fluorescein corneal staining (FL) score, tear film break-up time (TBUT), Schirmer’s test, and ocular symptoms questionnaire score (dry eye questionnaire score, DEQS) were evaluated. Furthermore, the correlation between these parameters and the concentrations of gal-3 in tears (ng/µg) and the detection rate of gal-3C (%) were analyzed. Gal-3 concentration in tears was positively correlated with the LG score (R = 0.60, p < 0.01), FL score (R = 0.49, p < 0.01), and DEQS (R = 0.45, p < 0.01), and negatively correlated with the TBUT score (R = −0.40, p < 0.01) and Schirmer’s I value (R = −0.36, p < 0.01). The detection rate of gal-3C in tears was significantly associated with the severity of DED, especially with the LG (p < 0.01) and FL (p < 0.01) scores. Therefore, the concentration of gal-3 and the detection rate of gal-3C in tears had a significant relationship with the severity of ocular surface barrier disruption.

Outcomes of Sjögren's versus non-Sjögren's related dry eye in a longitudinal, tertiary clinic-based sample.

PurposeTo assess the long-term treatment outcomes of dry eye in patients with and without underlying primary Sjögren’s syndrome (SS).DesignRetrospective longitudinal cohort.MethodsSS and non-SS dry eye patients with clinic visits for a minimum of 5 consecutive years at a tertiary, dedicated dry eye clinic were included. Electronic health records were reviewed to collect data regarding demographics, objective dry eye parameters, treatments utilized at baseline and final visit, and corneal complications observed during follow-up.ResultsTwo hundred and two patients (101 SS and 101 randomly selected non-SS), with a mean follow-up of 7.1 years were included. At baseline, mean conjunctival lissamine green staining score was 2.9 and mean corneal fluorescein staining score was 2.0. At last visit, notable improvement in staining score for cornea (–1.1, P < .001) and conjunctiva (–1.8, P < .001) was seen equally in both dry eye groups. Most patients (88.1%) had an escalation of treatment by the final visit, with similar rates in both groups (P = .51). Half (48.9%) of the patients had no conjunctival staining, and a third (34.4%) had no corneal staining at their last visit. Twenty (9.9%) patients experienced a vision-threatening corneal complication, including ulcers and melt, with no difference in occurrences between the groups (P = .64).ConclusionsThe majority of patients in this longitudinal, tertiary clinic-based sample demonstrated improvement in their ocular surface staining score by the final visit with escalation in treatment. Treatments used, improvement achieved, and corneal complication rates leading to loss of vision were similar in both SS and non-SS dry eye groups.

Improving ocular surface comfort in contact lens wearers

PurposeContact lens discomfort (CLD) is a major concern that can lead to the decreased or abandoned use of contact lenses. Contact lens users with dry eye disease are more likely to present with CLD. This study was conducted to evaluate the efficacy of a bioprotective preservative free, hypotonic, 0.15% hyaluronic acid (HA)-3% Trehalose artificial tear in managing dry eye symptoms in contact lens wearers. MethodsA prospective, single-arm, observational pilot study to evaluate the effectiveness of treatment with HA-Trehalose artificial tears in contact lens wearers (N = 33) aged 18–45 years with symptoms of ocular discomfort. Participants used a preservative-free, hypotonic HA-Trehalose artificial tear (1 drop/4 times per day) for 84 days. Participants were assessed using Visual Analogue Scale (VAS) for dry eye symptoms (pain, photophobia, dry eye sensation, blurry vision, foreign body sensation, itching, tingling/burning, and sticky eye feeling), Ocular Surface Disease Index (OSDI), Contact Lens Dry Eye questionnaire (CLDEQ-8), Berkley Dry Eye Flow-Chart (DEFC) on Day 0 and Day 84 and tear break-up time (TBUT), ocular surface staining with fluorescein and lissamine green, tear meniscus evaluation, and visual acuity on Day 0, 35, and 84. ResultsAll VAS symptoms (except tingling/burning and sticky eye feeling), OSDI, CLEDQ-8, and DEFC showed statistically significant (p < 0.05) improvement from baseline (Day 0) to Day 84. Similarly, corneal (fluorescein) and conjunctival (lissamine green) quality improved during the study (p < 0.05 at Day 84 versus baseline). Tear break-up time (TBUT), conjunctival (lissamine green) staining, and tear meniscus decreased but the changes were not statistically significant. Visual acuity did not change during the study. There were no ocular or systemic adverse events. ConclusionsThis study showed that the instillation of a preservative-free, hypotonic, HA-Trehalose artificial tear in contact lenses wearers with dry eye syndrome significantly improved symptoms and reduced associated signs such as corneal and conjunctival staining.

Repository Corticotropin Injection (Acthar® Gel) for Refractory Severe Noninfectious Keratitis: Efficacy and Safety from a Phase 4, Multicenter, Open-Label Study.

IntroductionNoninfectious keratitis is a painful corneal inflammation treated with topical cyclosporine and other immunosuppressants. Additional treatment options are needed for keratitis that does not improve with standard therapies. Repository corticotropin injection (RCI; Acthar® Gel) is approved to treat severe acute and chronic allergic and inflammatory processes involving the eye and its adnexa, including keratitis. This phase 4, multicenter, open-label study assessed the efficacy and safety of RCI for refractory severe noninfectious keratitis.MethodsPatients were ≥ 18 years old with persistent severe keratitis despite treatment with topical immunosuppressants. Patients received 80 U of RCI subcutaneously twice weekly for 12 weeks followed by a 4-week taper. Assessments included all domains of the Impact of Dry Eye on Everyday Life (IDEEL) Questionnaire, Ocular Discomfort and 4-Symptom Questionnaire, and Visual Analog Scale (VAS). Corneal fluorescein and conjunctival lissamine green staining, Conjunctival Redness Scale, tear production (Schirmer’s test), visual acuity, slit lamp examination, and intraocular pressure were also assessed. Safety was evaluated via treatment-emergent adverse events. Analyses were performed using the modified intent-to-treat (mITT) population (patients who received ≥ 1 dose of RCI and contributed any post-baseline efficacy data).ResultsIn the mITT population (N = 35), 50.0% (95% confidence interval, 33.2% to 66.8%) of patients experienced clinically important improvements in the symptom bother domain of the IDEEL Questionnaire at week 12 of RCI therapy. All domains of the IDEEL and the Ocular Discomfort and 4-Symptom Questionnaire showed improvements at week 12 of RCI treatment. The most pronounced improvements in the VAS at week 12 were for eye dryness and eye discomfort. Corneal staining, conjunctival staining, conjunctival redness, and tear production showed early improvements that were sustained through week 12. No new safety signals for RCI were identified.ConclusionsRCI is safe and effective for refractory severe noninfectious keratitis that has not improved with other approved therapies.Trial registration numberClinicalTrials.gov NCT04169061.Supplementary InformationThe online version contains supplementary material available at 10.1007/s40123-021-00400-y.

Is there a role for tapered topical dose steroidal treatment for dry eye disease? A randomized, pilot study.

To evaluate the effect of tapered doses of loteprednol-etabonate in dry eye disease patients. Dry eye and treatment outcomes were assessed by Schirmer I test, tear BUT, lissamine green conjunctival staining, fluorescein corneal staining, and HLA-DR expression on conjunctival cells. Patients received either loteprednol-etabonate 0.5% twice daily for 14 days tapered to once daily for 14 days, and then twice weekly for 28 days (n = 10), or NaCl 0.9%. A significant decrease of ocular surface inflammation and improvement of symptoms was recorded in the study group compared with controls at days 14 and 56. Change from baseline in HLA-DR expression in CD45+ conjunctival cells was significantly higher in treated patients at day 14. Intraocular pressure and best corrected visual acuity were preserved in all treated eyes. Tapered doses of loteprednol etabonate 0.5% suspension controlled ocular surface inflammation, improving dry eye symptoms.

Canonical Grading Scales of Corneal and Conjunctival Staining Based on Psychophysical and Physical Attributes.

PurposeIn this study, we apply psychophysical scaling principles based on physical (photometric) attributes of images to better understand the factors involved in clinician judgement of ocular surface staining and, using that knowledge, to develop photographic scales for the assessment of staining for dry eye (DE) and related conditions.MethodsSubjects with noninfectious ocular surface staining were enrolled at five clinical sites. Following instillation of fluorescein, photographs of corneal staining were taken every 30 seconds for at least 5 minutes. The same procedure was followed for conjunctival staining after instillation of 2 µl of 1% lissamine green. A subset of the best corneal and bulbar conjunctival staining images were anonymized and a spectroradiometer measured photometric attributes (luminance and chromaticity). The images were scaled psychophysically by study investigators, who participated in constructing grading scales based on physical and psychophysical analyses. The final grading scales were refined following consultation with outside DE experts.ResultsPhotographs were collected from 142 subjects (81% women), with an average age of 58 ± 17 years; 89% were diagnosed with DE. There was a monotonic relationship between between physical measurements and psychophysically scaled staining of both corneal (fluorescein) and bulbar (lissamine green) staining. Michelson contrast and u’ (chromaticity) accounted for 66% and 64% of the variability in the psychophysically scaled images of fluorescein corneal and lissamine green conjunctival staining, respectively.Translational RelevanceThis paper provides examples of the first ever clinically usable ocular surface staining scales validated using psychophysical scaling and the physical attributes (luminance and chromaticity) of the staining itself. In addition, it provides a generalizable method for the development of other clinical scales of ocular appearance.

Ocular Surface Pathology in Patients Suffering from Mercury Intoxication.

Purpose: To report the ocular surface pathology of patients suffering from acute/subacute mercury vapor intoxication. Design: Cross-sectional study. Participants: Male workers intoxicated with inorganic mercury referred for ophthalmic involvement and healthy control subjects. Methods: The following tests were performed: dry eye (DE)-related symptoms indicated by the ocular surface disease (OSDI) index questionnaire; tear osmolarity; analysis of 23 tear cytokine concentrations and principal component and hierarchical agglomerative cluster analyses; tear break-up time (T-BUT); corneal fluorescein and conjunctival lissamine green staining; tear production by Schirmer and tear lysozyme tests; mechanical and thermal corneal sensitivity (non-contact esthesiometry); and corneal nerve analysis and dendritic cell density by in vivo confocal microscopy (IVCM). Results: Twenty-two out of 29 evaluated patients entered the study. Most had DE-related symptoms (OSDI values > 12), that were severe in 63.6% of them. Tear osmolarity was elevated (>308 mOsms/L) in 83.4% of patients (mean 336.23 (28.71) mOsm/L). Corneal and conjunctival staining were unremarkable. T-BUT was low (<7 s) in 22.7% of patients. Schirmer test and tear lysozyme concentration were low in 13.6% and 27.3% of cases, respectively. Corneal esthesiometry showed patient mechanical (mean 147.81 (53.36) mL/min) and thermal thresholds to heat (+2.35 (+1.10) °C) and cold (−2.57 (−1.24) °C) to be significantly higher than controls. Corneal IVCM revealed lower values for nerve density (6.4 (2.94) n/mm2), nerve branching density (2 (2.50) n/mm2), and dendritic cell density (9.1 (8.84) n/mm2) in patients. Tear levels of IL-12p70, IL-6, RANTES, and VEGF were increased, whereas EGF and IP-10/CXCL10 were decreased compared to controls. Based on cytokine levels, two clusters of patients were identified. Compared to Cluster 1, Cluster 2 patients had significantly increased tear levels of 18 cytokines, decreased tear lysozyme, lower nerve branching density, fewer dendritic cells, and higher urine mercury levels. Conclusions: Patients suffering from systemic mercury intoxication showed symptoms and signs of ocular surface pathology, mainly by targeting the trigeminal nerve, as shown by alterations in corneal sensitivity and sub-basal nerve morphology.

Systemic Conditions Associated with Severity of Dry Eye Signs and Symptoms in the Dry Eye Assessment and Management Study

Certain systemic conditions are reported to be risk factors for dry eye disease (DED), but their associations with DED severity are not well studied. We evaluated whether systemic conditions reported to be DED risk factors are associated with severity of DED signs and symptoms. Secondary analysis of data from the Dry Eye Assessment and Management Study, a large-scale multicenter randomized clinical trial of patients with moderate to severe DED. Five hundred thirty-five adult patients with moderate to severe DED from 27 United States centers. Patients reported their medical history at baseline. They underwent ocular surface examinations and symptom evaluation using standardized protocols at baseline, 6 months, and 12 months. We analyzed the associations of systemic conditions (a systemic disease or smoking history) reported as potential DED risk factors with the severity of DED signs and symptoms using generalized linear regression models adjusted by age, gender, race, and visit. Dry eye disease symptoms assessed using the Ocular Surface Disease Index (OSDI), 6 DED signs (tear film break-up time, anesthetized Schirmer testing, corneal fluorescein staining, conjunctival lissamine green staining, tear osmolarity, and meibomian gland dysfunction), and a composite signs severity score from 0 to 1 (1= most severe). The mean age was 58 years; 81% were women. More severe DED signs were associated significantly with Sjögren syndrome (mean composite signs severity score 0.52 with disease vs. 0.43 without disease; P < 0.001), facial rosacea (0.47 vs. 0.43; P= 0.002), rheumatoid arthritis (0.47 vs. 0.42; P= 0.002), peripheral artery disease (0.50 vs. 0.43; P < 0.001), and daily smoking history (0.45 vs. 0.43; P= 0.047). Thyroid dysfunction, osteoarthritis, diabetes, irritable bowel syndrome, hypercholesterolemia, hypertension, and hypertriglyceridemia were not associated significantly with DED signs. No conditions were associated significantly with OSDI. In this large, well-characterized cohort of patients with DED assessed under standardized procedures, patients with certain systemic diseases and smoking history showed more severe DED signs compared with patients without the conditions. The profile of significant DED signs varied by systemic condition, reflecting different DED causes. Understanding the systemic conditions and underlying causes that predispose some patients to severe DED can improve management.