Keratoconjunctival Staining Scores Research Articles

Clinical efficacy of diquafosol sodium 3% versus hyaluronic acid 0.1% in patients with dry eye disease after cataract surgery: a protocol for a single-centre, randomised controlled trial

IntroductionThe number of cataract surgeries, the most common ophthalmic surgery, is expected to increase due to ageing populations. Dry eye disease (DED) is a frequent side effect of cataract surgery,...

A multicenter cross-sectional survey of dry eye clinical characteristics and practice patterns in Korea: the DECS-K study.

To compare the proportions of patients satisfying Korean dry eye guidelines and Asia Dry Eye Society (ADES) diagnostic criteria and to describe the clinical characteristics and practice patterns of dry eye patients in Korea. Prospective observational study. This study enrolled 160 patients, with 158 patients analyzed. ADES guidelines were applied to dry eye patients satisfying the Korean dry eye guidelines. Risk factors for dry eye (e.g. visual display terminal [VDT] use) were evaluated. Dry eye subtypes were categorized as aqueous-deficient or evaporative. Objective signs (e.g. corneal and keratoconjunctival staining scores, tear break-up time [TBUT], and Schirmer test) and symptoms (Dry Eye-Related Quality of Life Score [DEQS] and Ocular Surface Disease Index [OSDI] questionnaire) were evaluated. Treatment patterns were also recorded. Patients (mean age 43.1years) were mainly women (85.4%), with a high proportion (77.2%) of VDT users. Concordance between Korean and ADES guidelines was high (94.3%), with most patients (94.3%) having tear film instability (TBUT ≤ 5s). Evaporative dry eye occurred in 60.1% and aqueous-deficient in 39.9% of cases. Objective signs were significantly better in evaporative than in aqueous-deficient dry eye. The DEQS bothersome ocular symptoms' score was significantly higher in VDT users than in non-users. OSDI symptom severity and DEQS were significantly correlated (p < 0.001). The most common treatments were hyaluronic acid (33.5%) and diquafosol (15.2%), the latter used mainly for mild and evaporative dry eye. The study showed high concordance between Korean and ADES diagnostic guidelines, with most patients having tear film instability.

Association of Systemic Comorbidities with Dry Eye Disease.

We investigated the association between dry eye disease and systemic comorbidities, including dry eye subtype, quality of life (QOL) and health utility among patients with dry eye disease. This cross-sectional, observational study enrolled 449 patients with dry eye disease (386 females; mean age, 62.6 ± 15.7 [range, 21–90] years). Ophthalmic examination findings included tear film break-up time (TBUT), Schirmer I value and keratoconjunctival staining score. QOL and health utility were evaluated using the Dry Eye-Related Quality-of-Life Score (DEQS) and Human Utility Index Mark 3 (HUI-3), respectively. Background information, including systemic comorbidities, was obtained. Prevalence of systemic comorbidities was 48.8% (219/449). No significant difference occurred between DEQS and systemic comorbidity. However, patients with dry eye disease and systemic comorbidities (depression and insomnia) exhibited significantly worse ocular surface parameters, particularly regarding TBUT, than those without. Dry eye disease with insomnia or depression comorbidity significantly correlated with friction-related diseases (including conjunctivochalasis or lid wiper epitheliopathy). A high prevalence of several systemic comorbidities occurred in patients with dry eye disease. This study shows an association between ocular signs and systemic comorbidities, particularly depression and insomnia. Ophthalmologists should be aware of patients’ systemic comorbidities in the diagnosis and management of dry eye disease.

Persistently Worsened Tear Break-up Time and Keratitis in Unilateral Pseudophakic Eyes after a Long Postoperative Period.

Dry eye disease may develop and persist after cataract surgery; however, unilateral cases have not been fully documented. This cross-sectional, observational study was conducted in five eye clinics in Japan. A total of 1023 outpatients were initially enrolled, and 89 unilateral pseudophakic subjects with 1+ year of follow-up after uncomplicated cataract surgery were included. The tear break-up times (TBUTs) and keratoconjunctival staining results were compared between phakic and pseudophakic eyes. The mean age of the patients was 69.3 ± 10.4 years (32 men, 36.0%), and the mean postoperative period was 4.6 ± 4.4 (1–20) years. For the ophthalmic parameters, the TBUTs were 4.4 ± 1.9 and 3.8 ± 1.9 s (p < 0.001), the keratoconjunctival staining scores were 0.11 ± 0.38 and 0.22 ± 0.56 (p = 0.02), the spherical equivalents were −1.27 ± 2.51 and −0.99 ± 1.45 D (p = 0.21), the astigmatic errors were 0.79 ± 0.66 and 0.78 ± 0.58 D (p = 0.80), and the intraocular pressures were 13.6 ± 2.9 and 13.5 ± 2.6 mmHg (p = 0.62) for the phakic and pseudophakic eyes, respectively. The corneal status was significantly worse in the pseudophakic eyes than in the contralateral phakic eyes, even after more than one year after implant surgery. The present results suggested that long-term ocular surface problems should be examined further since they may not originate only from surgery or postoperative ocular surface diseases.

Long-Term Safety and Effectiveness of Diquafosol for the Treatment of Dry Eye in a Real-World Setting: A Prospective Observational Study.

IntroductionDiquafosol is a P2Y2 receptor agonist that has been shown to be effective in the treatment of dry eye disease (DED) in short-term studies; however, its long-term safety and effectiveness have not been evaluated in a real-world setting.MethodsThis prospective, multicentre, open-label observational study was conducted in patients with DED over 12 months. Safety endpoints included the incidence of adverse drug reactions (ADRs) and serious ADRs. Effectiveness endpoints included change from baseline in keratoconjunctival staining score, tear film break-up time (BUT) and Dry Eye-related Quality of Life Score (DEQS).ResultsA total of 580 patients were included, most of whom were female (82.9%). The proportion of patients who completed 12 months of observation was 55.0%, the most common reason for discontinuation was patient decision (54.6%). The incidence of ADRs was 10.7% and was highest during the first month of treatment (5.5%); no serious ADRs were reported. Compared with baseline, significant improvements in all effectiveness outcomes, including keratoconjunctival fluorescein staining score, BUT and DEQS summary score, were observed at each evaluation during the treatment period (p < 0.001).ConclusionThe present, real-world study showed that diquafosol 3.0% ophthalmic solution was well tolerated and effective in the long-term treatment of DED.Electronic supplementary materialThe online version of this article (10.1007/s12325-019-01188-x) contains supplementary material, which is available to authorized users.

Discrepancies in Persistent Dry Eye Signs and Symptoms in Bilateral Pseudophakic Patients.

Despite the increased awareness of early prophylaxis and treatment for dry eye disease (DED) during the first few weeks after cataract surgery, the chronic effect of cataract surgery on the risk of ocular surface abnormalities has not been fully explored. This study was to assess the prevalence of DE subjective symptoms and clinical tests according to the cataract surgery. A total of 172 patients who underwent bilateral cataract surgeries at least 5 months before the recruitment date and 1225 controls with no cataracts were evaluated for their subjective DE symptoms (dry sensation, foreign-body sensation, ocular pain, ocular fatigue, sensitivity to bright light, and blurred vision) and ophthalmic parameters (tear break-up time, keratoconjunctival staining scores, and maximum blinking interval). The presence of subjective DE symptoms was generally inversely associated with cataract surgeries, whereas abnormal clinical tests were more pronounced among postsurgical cataract patients than among controls. Pseudophakic patients showed a 57% increased prevalence of severe keratoconjunctivitis, compared to controls (P = 0.02). In contrast, among subjective DE symptoms, significantly lower odds of sensitivity to bright light were detected among cases than controls; the multivariable-adjusted odds ratio (95% confidence interval) comparing pseudophakic patients with noncataract patients was 0.56 (0.34–0.92) (P = 0.02). In conclusion, persistent tear instability and corneal epitheliopathy were found even at several months or more after cataract surgery. This study demonstrates the importance of evaluating ocular surface conditions in pseudophakic patients, even if they lack DE symptoms.

Quality of life measures and health utility values among dry eye subgroups

BackgroundTo determine whether quality of life (QOL) and health utility are affected to the same extent among dry eye (DE) patients with short tear film break-up time dry eye (TBUT-DE) with minimal clinical signs were as severe as aqueous-deficient dry eye (ADDE).MethodsA multicenter cross-sectional study was conducted among DE patients who visited one of 10 eye clinics in Japan. Among the 463 registered patients, this study involved 449 patients with DE who were aged 20 years or older. Ophthalmic examination findings were assessed, including tear film break-up time (TBUT), Schirmer I value, and keratoconjunctival staining score. QOL was evaluated with the Dry Eye-Related Quality-of-Life Score (DEQS; 0 [best], 100 [worst]) and health utility (1 [total health], 0 [worst]) with the Health Utilities Index Mark 3 (HUI-3); scores were stratified by DE subgroup.ResultsMedian (interquartile range) of DEQS and HUI-3 scores across all participants were 21.7 (10.0–40.0) and 0.82 (0.69–0.91), respectively. Median (interquartile range) DEQS and HUI-3 scores in the ADDE group were 23.3 (10.0–40.0) and 0.79 (0.69–0.88), respectively; those in the short TBUT-DE group were 23.3 (13.3–38.3) and 0.82 (0.74–0.92), respectively. There were no significant between-group differences in questionnaire scores. Among the ophthalmic examination findings, a weak significant correlation between TBUT, corneal staining score and keratoconjunctival staining score to DEQS; TBUT and Schirmer test values to HUI-3, were seen.ConclusionsThe burden of short TBUT-DE on QOL as assessed by the DEQS and HUI-3 was as severe as that in ADDE. Our findings suggest that clinicians should be aware of the impact of short TBUT-DE on patients QOL and utility values.Trial registrationUniversity Hospital Medical Information Network (registration no. UMIN 000015890). Registered 10th December 2014, retrospectively registered.

The effect of rebamipide ophthalmic suspension on ocular surface mucins in soft contact lens wearers.

To evaluate the changes in ocular surface mucins with 2%rebamipide ophthalmic suspension treatment in soft contact lens (SCL) wearers. Rebamipide suspension is a mucin secretagogue approved for the treatment of dry eye syndrome in Japan. In this study, the fluorescence intensity of wheat germ agglutinin conjugate of fluorescein (F-WGA) was used as a marker of membrane-associated mucins, and sialic acid concentration in tear fluids as a marker of secreted mucins. Thirty-two eyes of 16 SCL wearers with discomfort were treated with rebamipide suspension at a dose of one drop in each eye four times daily for two weeks. The parameters of clinical efficacy were tear break-up time, fluorescein staining scores for the cornea and conjunctiva, and Schirmer test values. Fluorescence intensities in the central cornea were measured by fluorophotometry after the application of 5% F-WGA solution. Tears collected by Schirmer test strips were analyzed by high-performance liquid chromatography, and the concentrations of sialic acid, total protein, and the four major tear proteins, namely secretory IgA, lactoferrin, lipocalin-1, and lysozyme were measured. Significant increases in F-WGA fluorescence intensities (p < 0.005) were seen in the corneal surfaces. Sialic acid concentrations increased over time; however, the differences were not statistically significant. Except for a slight increase in kerato-conjunctival staining scores (p < 0.05) and secretory IgA (p < 0.05), no other significant differences were seen among clinical parameters or tear proteins. Topical application of rebamipide suspension significantly increased F-WGA intensity, a marker of membrane-associated mucins in SCL wearers.

A Clinic-based Survey of Clinical Characteristics and Practice Pattern of Dry Eye in Japan.

The aim of this study was to investigate the clinical characteristics and practice pattern of patients with dry eye disease (DED) in eye clinics across Japan. A multi-center, cross-sectional study was conducted among patients with DED who visited eye clinics in Japan. Subjective symptoms, patient's background, ocular surface features, and tear function were evaluated. Main outcome measures were tear break-up time (TBUT), Schirmer I value, kerato-conjunctival staining score, and dry eye symptom questionnaire score. Initially, 463 subjects were enrolled, and 449 cases (63 male and 386 female; mean age, 62.6±15.7years) were included in the final analysis. Overall, 94.9% of patients had a shortened TBUT (≤5s), and 54.6% had an aqueous tear deficiency (Schirmer I value ≤5mm). The most prevalent subtype of dry eye was aqueous-deficient dry eye, which was present in 35.0% of all patients, followed by short-BUT-type dry eye, which was seen in 26.7%. The two most common DED subtypes were aqueous-deficient and short-BUT-type dry eye. Shortened TBUT is the most common feature of dry eye, regardless of subtype. The current treatment choice mainly consisted of hyaluronic acid, two novel mucin secretagogues, diquafosol and rebamipide, and steroidal eye drops. University Hospital Medical Information Network: UMIN (registries no. UMIN 000015890). Japan Dry Eye Society, Tokyo, Japan, and Santen Pharmaceutical Co., Ltd., Osaka, Japan.

Influence of Ophthalmic Solutions on Tear Components.

Tear fluids are a mixture of secretions derived from lacrimal glands, accessory lacrimal glands, conjunctiva, and meibomian glands. Compositional changes to tears occur in the normal state and during ocular surface disease, such as dry eye conditions. We have investigated compositional changes to tears after topical application of ophthalmic solutions, with regard to tear-specific proteins (secretory immunoglobulin A, lactoferrin, lipocalin-1, and lysozyme) and ocular surface mucin in normal and dry eye conditions using high-performance liquid chromatography. After application of saline solution (0.9% sodium chloride) in normal subjects, transient but significant decreases in all tear components were observed. The recovery of protein concentrations took up to 30 minutes and lasted longer when the saline solution was applied more frequently. When applying ophthalmic solutions, a balance between washout and dilutional effects should be considered in addition to the therapeutic effect. Investigation of the effect of diquafosol solution (3%) in normal subjects revealed a significant increase in sialic acid concentration, a marker of ocular mucin, at 5 minutes after application, whereas a significant decrease was observed with saline. This result indicates the accelerated secretion of mucin from ocular tissues induced by diquafosol. A clinical study to determine the efficacy of diquafosol in patients with dry eye revealed improvements in tear breakup time, keratoconjunctival staining scores, and Schirmer test score, accompanied by an increase in sialic acid concentration in tears. Investigating normal and dry eye conditions through tear analysis may clarify the pathophysiology of dry eye conditions and support the efficacy of treatments.

Diquafosol for Soft Contact Lens Dryness: Clinical Evaluation and Tear Analysis.

To evaluate the efficacy of topical application of 3% diquafosol tetrasodium solution for the treatment of soft contact lens (SCL) wearers with dryness. In addition to clinical tests and subjective symptoms, we assessed the fluorescence intensity of wheat germ agglutinin conjugate of fluorescein (F-WGA) used as a marker of membrane-associated mucins and sialic acid concentration in tear fluids as a marker of secreted mucins. Twelve SCL wearers with dryness symptoms were treated with diquafosol for 4 weeks. Clinical tests included the tear film break-up time (BUT), corneal and conjunctival fluorescein staining scores, and Schirmer values. Subjective symptoms were evaluated by the Dry Eye-Related Quality-of-Life Score (DEQS). Fluorescence intensities in the central cornea were measured by fluorophotometry at 5 minutes after a 5% F-WGA solution was applied to the eye. The tears collected by the Schirmer test strips were analyzed by high-performance liquid chromatography (HPLC), and the concentrations of sialic acid; total protein; and the four major tear proteins secretory IgA, lactoferrin, lipocalin-1, and lysozyme proteins were measured. Comparing the results before and after diquafosol treatment, BUT (p < 0.01), kerato-conjunctival staining score (p < 0.05), corneal staining score (p < 0.05), and DEQS score (p < 0.01) showed statistically significant improvements. The F-WGA fluorescence intensities (p < 0.0001) significantly increased after treatment, whereas the concentrations of sialic acid and tear proteins remained unchanged. Topical application of diquafosol solution to the SCL wearers with dryness improved biomarker of membrane-associated mucins, BUT, staining of cornea and conjunctiva, and subjective symptoms.

Diquafosol sodium ophthalmic solution for the treatment of dry eye: clinical evaluation and biochemical analysis of tear composition.

To evaluate the clinical efficacy of 3% diquafosol sodium ophthalmic solution for dry eye, and to analyze the concentration of tear proteins and mucin-like substances after the treatment. Fifty eyes of 25 patients with dry eye syndrome were prospectively enrolled. The patients were treated with diquafosol solution at a dose of 1 drop in each eye 6 times daily for 4 weeks. The parameters of clinical efficacy were tear osmolarity, tear breakup time (BUT), fluorescein staining scores for the cornea and conjunctiva, Schirmer test values, and subjective symptoms evaluated using the ocular surface disease index (OSDI). Tears collected with Schirmer test strips were analyzed by high-performance liquid chromatography, and the concentrations of the total protein and the 4 major tear proteins, namely, secretory IgA, lactoferrin, lipocalin-1, lysozyme, and N-acetyl-neuraminic acid (Neu5Ac), were measured. Neu5Ac is a major sialic acid, a marker of secretory mucins. The BUT, keratoconjunctival staining scores, and Schirmer test values were improved with statistical significance after the treatment with diquafosol solution, while changes in the other parameters, including tear osmolarity, corneal staining scores, and OSDI scores were not significant. The Neu5Ac concentration was significantly increased, which was not accompanied by changes in tear proteins. Topical application of diquafosol significantly improved the clinical parameters of the BUT, keratoconjunctival staining scores, and Schirmer test values and was accompanied by increased sialic acid content in the tears of patients with dry eye.

Meibum Color and Free Fatty Acid Composition in Patients With Meibomian Gland Dysfunction.

We measured the components of meibum in patients with meibomian gland dysfunction (MGD) and control subjects and then examined the relation between meibum composition and clinical parameters. Thirty-eight patients with MGD (13 men and 25 women; mean age ± SD, 66.9 ± 15.0 years) and 20 control subjects (8 men and 12 women; 64.5 ± 6.7 years) were enrolled. Ocular symptom score, keratoconjunctival staining score, tear film breakup time, and Schirmer's test value were determined. Lid margin abnormalities and meibomian gland morphology were assessed for upper and lower eyelids, and meibum properties were evaluated at temporal, central, and nasal sites of each lid. Free fatty acid (FFA) composition of meibum was analyzed by liquid chromatography-Fourier transform mass spectrometry. Upper meibum color score was significantly correlated with epiphora and sticky sensation in MGD patients. Meibum grade, color, or viscosity did not differ significantly among the sites evaluated. A total of 103 species of FFA--including very long chain (such as C36 and C37) and odd-numbered chain (such as C17, C19, and C21) FFAs--were detected in meibum. Free fatty acid composition differed between clear and colored (cloudy or yellow) meibum, with unsaturated FFAs tending to be more abundant in colored meibum. Free fatty acid composition of human meibum correlates with meibum color as determined with a slit-lamp microscope. This finding may provide insight into the pathogenesis of MGD.