Late-Onset Traumatic Corneal Conjunctival Epithelial Disorders due to Granular Formation After Cosmetic Suture Blepharoplasty.

PURPOSE: The purpose of this study was to report conjunctival granular formation as one of the causative factors of a traumatic corneal conjunctival epithelial disorder after plastic suture blepharoplasty. METHODS: Clinical charts of 7 patients who had visited Ohshima Eye Hospital with a symptomatic corneal epithelial disorder and history of suture blepharoplasty were reviewed. Clinical evidence of conjunctival granular formations was observed in all patients at the tarsal conjunctiva facing to corneal conjunctival traumatic epithelial disorders. The desired outcome was to alleviate the disorder. The assessment included tabulating results after the placement of a soft contact lens bandage and subsequent partial tarsal plate resection of the granular formation. RESULT: Seven women (mean age 45.0 ± 10.9 years) enrolled in this study had previously undergone suture blepharoplasty (mean 18.3 ± 6.9 years before). Soft contact lens bandages relieved all of the patients' complaints immediately. After resecting the granular formation, the traumatic corneal conjunctival epithelial disorder disappeared, and no recurrence was observed after surgery. CONCLUSIONS: The conjunctival granular formation within the tarsal conjunctiva after suture blepharoplasty caused the late-onset traumatic corneal conjunctival epithelial disorder. A complete cure was obtained after resection of the granular formation at the tarsal conjunctiva. To the best of our knowledge, this is the first report to identify the removal of granular formations in 7 patients with late-onset traumatic corneal conjunctival disorders many years after blepharoplasty. The resection of these lesions is a promising procedure to treat late-onset ocular epithelial disorder after suture blepharoplasty.

Exploratory Search for Characteristic Symptoms to Distinguish Meibomian Gland Dysfunction from Dry Eye in a Population-Based Study in Japan.

Symptom overlap between meibomian gland dysfunction (MGD) and dry eye (DE) makes it difficult to distinguish between these two conditions on the basis of symptoms alone. We searched for characteristic symptoms that might help to distinguish MGD from DE on the basis of a population-based study. Subjects comprised 311 residents of Takushima island (18 to 96 years), including 117 individuals with MGD and 114 with DE. Responses to a symptom-related questionnaire (19 items) were subjected to factor analysis, and univariate regression analysis was performed to identify ocular surface parameters associated with characteristic symptoms of MGD. Factor analysis revealed aggregation of symptoms according to three factors: Factor 1 related to Symptom Score, Factor 2 to DE, and Factor 3 to MGD. Symptoms associated with DE included 11 items, whereas the only item related to MGD was tearing sensation. Pearson's correlation analysis revealed that tearing sensation was associated with tear meniscus height (TMH), noninvasive tear-film breakup time, fluorescein staining score, meiboscore, meibum grade, and Schirmer value. Subjects with MGD experienced significantly more tearing and had a larger TMH than did those without MGD (p = 0.0334). Tearing sensation may thus be a characteristic symptom of MGD. Physicians should suspect MGD who complain of tearing sensation.

Prediction of cycloplegic refraction for noninvasive screening of children for refractive error.

Detection of refractive error in children is crucial to avoid amblyopia and its impact on quality of life. We here performed a retrospective study in order to develop prediction models for spherical and cylinder refraction in children. The enrolled 1221 eyes of 617 children were divided into three groups: the development group (710 eyes of 359 children), the validation group (385 eyes of 194 children), and the comparison group (126 eyes of 64 children). We determined noncycloplegic and cycloplegic refraction values by autorefractometry. In addition, several noncycloplegic parameters were assessed with the use of ocular biometry. On the basis of the information obtained from the development group, we developed prediction models for cycloplegic spherical and cylinder refraction in children with the use of stepwise multiple regression analysis. The prediction formulas were validated by their application to the validation group. The similarity of noncycloplegic and predicted refraction to cycloplegic refraction in individual eyes was evaluated in the comparison group. Application of the developed prediction models for spherical and cylinder refraction to the validation group revealed that predicted refraction was significantly correlated with measured values for cycloplegic spherical refraction (R = 0.961, P < 0.001) or cylinder refraction (R = 0.894, P < 0.001). Comparison of noncycloplegic, cycloplegic, and predicted refraction in the comparison group revealed that cycloplegic spherical refraction did not differ significantly from predicted refraction but was significantly different from noncycloplegic refraction, whereas cycloplegic cylinder refraction did not differ significantly from predicted or noncycloplegic values. Our prediction models based on ocular biometry provide estimates of refraction in children similar to measured cycloplegic spherical and cylinder refraction values without the application of cycloplegic eyedrops.

Relation of Dietary Fatty Acids and Vitamin D to the Prevalence of Meibomian Gland Dysfunction in Japanese Adults: The Hirado-Takushima Study.

Intervention studies have shown that n-3 polyunsaturated fatty acid (PUFA) supplementation is effective for the treatment of meibomian gland dysfunction (MGD). Ointment containing an analog of vitamin D has also been found to improve symptoms and signs of MGD. We have now evaluated the relation of MGD prevalence to dietary intake of fatty acids (FAs) and vitamin D among a Japanese population. Subjects comprised 300 adults aged 20 to 92 years residing on Takushima Island. MGD was diagnosed on the basis of subjective symptoms, lid margin abnormalities, and meibomian gland obstruction. Dietary FA and vitamin D intake was estimated with a brief-type self-administered diet history questionnaire. MGD prevalence was 35.3%. Multivariate adjusted odds ratios (95% confidence intervals) between extreme quintiles of intake for MGD prevalence were 0.40 (0.16-0.97) for total fat, 0.40 (0.17-0.97) for saturated FAs, 0.40 (0.17-0.97) for oleic acid, 0.52 (0.23-1.18) for n-3 PUFAs, 0.63 (0.27-1.49) for n-6 PUFAs, 1.32 (0.59-2.95) for the n-6/n-3 PUFA ratio, and 0.38 (0.17-0.87) for vitamin D. Total fat, saturated FA, oleic acid, and vitamin D intake may thus be negatively associated with MGD prevalence in the Japanese.

Multicenter Study of Intense Pulsed Light for Patients with Refractory Aqueous-Deficient Dry Eye Accompanied by Mild Meibomian Gland Dysfunction.

Aqueous-deficient dry eye (ADDE) and meibomian gland dysfunction (MGD) can be refractory to therapy. Intense pulsed light (IPL) was recently introduced as an effective treatment for MGD. We here evaluated the efficacy of IPL combined with MG expression (MGX) compared with MGX alone (n = 23 and 20, respectively) for patients with refractory ADDE with mild MGD at three sites. Symptom score, visual acuity (VA), noninvasive breakup time (NIBUT) and lipid layer thickness (LLT) of the tear film, lid margin abnormalities, fluorescein BUT (FBUT), fluorescein staining, tear meniscus height (TMH), meibum grade, meiboscore, and Schirmer's test value were assessed at baseline and 1 and 3 months after treatment. LLT, plugging, vascularity, FBUT and NIBUT were improved only in the IPL-MGX group at three months compared with baseline. All parameters with the exception of VA, meiboscore, TMH, Schirmer's test value were also improved in the IPL-MGX group compared with the control group at three months, as was VA in patients with central corneal epitheliopathy. Although IPL-MGX does not affect aqueous layer, the induced improvement in quality and quantity of the lipid layer may increase tear film stability and ameliorate symptoms not only for evaporative dry eye but for ADDE.

Relations Among Corneal Curvature, Thickness, and Volume in Keratoconus as Evaluated by Anterior Segment-Optical Coherence Tomography.

Purpose: To provide insight into the mechanism underlying corneal deformation in keratoconus, we examined the relations among corneal curvature, thickness, and volume as well as the association of corneal scar formation with these parameters. Methods: A total of 288 corneas of 174 keratoconus patients and 114 corneas of 57 control subjects were examined by anterior segment-optical coherence tomography (AS-OCT). Anterior and posterior refractive values, corneal thickness (CT), and corneal volume (CV) were determined by AS-OCT for both control and keratoconic eyes. The pattern of corneal stromal scarring was also determined from the AS-OCT images. Results: The distribution of CV was similar for keratoconic and control eyes, whereas anterior and posterior refractive values as well as CT showed a wider distribution for keratoconic eyes. The progression of corneal deformation initially occurred without corneal thinning but was later associated with a decrease in CT and an eventual loss of CV. The progression of scarring from the anterior to the posterior stroma was associated with an increase in anterior refractive value and decreases in posterior refractive value, CT, and CV. Conclusions: The progression of keratoconus as reflected by corneal deformation was associated with a reduction in CT and CV as well as stromal scar formation. The loss of CV occurred after the initial decline in CT, suggesting that stromal degradation occurred only at the advanced stage of keratoconus.

Automated Measurement of Tear Meniscus Height with the Kowa DR-1α Tear Interferometer in Both Healthy Subjects and Dry Eye Patients.

Purpose: To develop and assess a method for quantitation of lower tear meniscus height (TMH) with the Kowa DR-1α tear interferometer. Methods: Sixty-nine eyes of 49 men and 20 women (36 healthy volunteers, 33 patients with aqueous-deficient dry eye [ADDE]; mean age ± SD, 50.0 ± 14.0 years) were enrolled. TMH of each subject was measured by two observers both with DR-1α and newly developed software and with anterior-segment swept-source optical coherence tomography (SS-OCT). Intraoperator repeatability and interoperator and intersession reproducibility of measurements were assessed based on the within-subject SD (Sw), coefficient of variation (CV), and intraclass correlation coefficient (ICC). Agreement between the two devices was assessed by regression and Bland-Altman analysis. Results: The CV for system repeatability of DR-1α was <2.0%. The CV for intraoperator repeatability and interoperator and intersession reproducibility for DR-1α measurements was ≤9.6%, ≤4.5%, and ≤4.4% in healthy subjects, respectively, and ≤16.8%, ≤9.8%, and ≤10.3% in ADDE patients. All corresponding ICC values were ≥0.87 in healthy subjects and ≥0.48 in ADDE patients. Bland-Altman plots indicated a high level of agreement between the two devices. Schirmer test value was significantly correlated with interferometric TMH in both healthy subjects (ß = 0.59, P < 0.001) and ADDE patients (ß = 0.47, P = 0.017). Conclusions: Tear interferometry allows measurement of TMH as reliably as does SS-OCT. DR-1α may inform not only the diagnosis of dry eye disease but also identification of disease subtype.

Meibomian Gland Dysfunction and Dry Eye Are Similar but Different Based on a Population-Based Study: The Hirado-Takushima Study in Japan.

PURPOSE: To evaluate the prevalence and risk factors of and the relationship between meibomian gland dysfunction (MGD) and dry eye (DE) in Japan. DESIGN: A population-based cross-sectional study. METHODS: Participants filled in questionnaires regarding ocular symptoms, systemic diseases, and lifestyle factors. Meibomian gland-related parameters and tear film-related parameters were evaluated. Risk factors for MGD and DE were analyzed by using univariate and multivariate logistic regression. Age-specific prevalence of MGD and DE was estimated by using a general additive model with degree-3 natural splines. The structural relation between MGD and DE was assessed by factor analysis using the principal components method and promax rotation. RESULTS: A total of 356 residents of Takushima Island (133 males, 223 females) at the mean ± SD age of 55.5 ± 22.4 years (range, 6-96 years) were enrolled. The prevalence of MGD and DE was 32.9% and 33.4%, respectively, with a coexistence rate of 12.9%. The prevalence of MGD was associated with male sex (odds ratio [OR], 2.42), age (OR per decade increment,1.53), and oral intake of lipid-lowering agents (OR, 3.22). The prevalence of DE was associated with female sex (OR, 3.36), contact lens wear (OR, 2.84), conjunctivochalasis (OR, 2.57), and lid margin abnormalities (OR, 3.16). The age-specific prevalence of MGD and DE differed, and factor analysis for 16 parameters showed that MGD and DE had independent hidden sources (interfactor correlation, -0.017). CONCLUSIONS: MGD and DE are common in this population. Although their ocular symptoms are similar, the pathogenesis of MGD differs from that of DE.

Therapeutic efficacy of intense pulsed light in patients with refractory meibomian gland dysfunction.

PURPOSE: To evaluate the efficacy and safety of intense pulsed light (IPL) combined with meibomian gland expression (MGX) for treatment of refractory meibomian gland dysfunction (MGD). METHODS: Ninety eyes of 45 patients were randomly assigned to receive either the combination of IPL and MGX or MGX alone (control). Each eye underwent eight treatment sessions at 3-week intervals. Parameters were evaluated before and during treatment as well as at 3-11 weeks after the last treatment session. Measured parameters included the Standard Patient Evaluation of Eye Dryness (SPEED) questionnaire score, noninvasive breakup time (NIBUT), fluorescein breakup time (BUT), lipid layer grade, lipid layer thickness (LLT), lid margin abnormalities, corneal and conjunctival fluorescein staining (CFS) score, meibum grade, and meiboscore. RESULTS: A significant improvement in lipid layer grade was apparent in the IPL-MGX group from 6 to 32 weeks after treatment onset (adjusted P < 0.001) but was not observed in the control group. The IPL-MGX group also showed significant improvements in LLT, NIBUT, BUT, lid margin abnormalities, and meibum grade compared with the control group at 24 and 32 weeks (adjusted P < 0.001) as well as significant improvements in the SPEED score at 32 weeks (adjusted P = 0.044) and in CFS score at 24 (adjusted P = 0.015) and 32 (adjusted P = 0.006) weeks. CONCLUSIONS: The combination of IPL and MGX improved homeostasis of the tear film and ameliorated ocular symptoms in patients with refractory MGD and is thus a promising modality for treatment of this condition.

Growth Suppression of Human Colorectal Cancer Cells with Mutated KRAS by 3-Deaza-cytarabine in 3D Floating Culture.

BACKGROUND/AIM: During screening for compounds that selectively suppress growth of human colorectal cancer (CRC) spheroids with mutant (mt) KRAS, the uridine analogue, 5-bromouridine (BrUrd) was identified and its derivatives were explored. MATERIALS AND METHODS: DNA incorporation in two-dimensional (2D) and three-dimensional floating (3DF) cultures was examined with the uridine analogue, 5-ethynyl-2'-deoxyuridine (EdU). The area of HKe3 CRC spheroids expressing wild type (wt) KRAS (HKe3-wtKRAS) and mtKRAS (HKe3-mtKRAS) were measured in 3DF culture with 11 BrUrd derivatives. RESULTS: EdU was strongly incorporated into newly-synthesized DNA from HKe3-mtKRAS cells compared to HKe3-wtKRAS in 2D and 3DF culture. 3-Deaza-cytarabine, which has properties of BrUrd and cytidine, was the most effective inhibitor of HKe3-mtKRAS spheroids with the least toxicity to HKe3-wtKRAS. Growth suppression of 3-deaza-cytarabine was stronger than cytarabine in 2D culture, and toxicity was lower than gemcitabine in long-term 3DF culture. CONCLUSION: 3-Deaza-cytarabine exhibits properties useful for the treatment of CRC patients with mtKRAS.

Multicenter Study of Intense Pulsed Light Therapy for Patients With Refractory Meibomian Gland Dysfunction.

PURPOSE: To evaluate the efficacy of intense pulsed light (IPL) therapy combined with meibomian gland expression (MGX) for refractory meibomian gland dysfunction (MGD) in a prospective study conducted at 3 sites in Japan. METHODS: Patients with refractory obstructive MGD were enrolled and underwent 4 to 8 IPL-MGX treatment sessions at 3-week intervals. Clinical assessment included the Standard Patient Evaluation of Eye Dryness questionnaire; noninvasive breakup time of the tear film and interferometric fringe pattern as determined by tear interferometry; lid margin abnormalities, fluorescein breakup time of the tear film, corneal and conjunctival fluorescein staining (CFS), and meibum grade as evaluated with a slit-lamp microscope; meibomian gland morphology (meiboscore); and tear production as measured by the Schirmer test without anesthesia. RESULTS: Sixty-two eyes of 31 patients (17 women, 14 men; mean age ± SD, 47.6 ± 16.8 years) were enrolled. The Standard Patient Evaluation of Eye Dryness score (P < 0.001), noninvasive breakup time (P < 0.001), and interferometric fringe pattern (P < 0.001) were significantly improved after therapy, with 74% of eyes showing a change in the interferometric fringe pattern from 1 characteristic of lipid deficiency to the normal condition. Meibum grade, lid margin abnormality scores, fluorescein breakup time, and CFS were also significantly improved (P < 0.001, P < 0.001, P < 0.001, and P = 0.002, respectively) after treatment, whereas the meiboscore and Schirmer test value remained unchanged. CONCLUSIONS: IPL-MGX ameliorated symptoms and improved the condition of the tear film in patients with refractory MGD and is therefore a promising treatment option for this disorder.

Optimization of fixative solution for retinal morphology: a comparison with Davidson's fixative and other fixation solutions.

PURPOSE: Numerous fixative solutions are available but many are not amenable to the histomorphological preservation of retinae. The investigators specifically focused on retinal histological studies, which rather than 4% formaldehyde (FA), often use Davidson's fixative. However the latter has its limitations. The purpose of this study was to produce a new fixative which maintains retinae closer to the in vivo conditions. STUDY DESIGN: Experimental design. METHODS: Four fixative formulations (4% paraformaldehyde, Davidson's fixative, modified Davidson's fixative and an in-house fixative - TB-Fix) were tested on retinae and the outcomes on histomorphology and immunohistochemical staining for selected antigenic markers was compared. RESULTS: TB-Fix markedly improved morphological detail following hematoxylin and eosin staining, most importantly eliminating the spongiform appearance in the plexiform layer and the swelling of somata (including Müller cells), when compared to FA, Davidson's fixative and its modified version. Retinal samples fixed with TB-Fix or FA showed comparable results in immunohistological staining for neurons and glia in the retina. Importantly, while the whole eye fixed with FA collapsed in shape and induced artificial retinal detachment, the eye fixed with TB-Fix avoided deformation and detachment. Furthermore, we found that TB-Fix also prevented detachment from the culture plate when used to fix HEK293 cells, which are known to detach from the plate easily. CONCLUSION: It was demonstrated that TB-Fix provides an overall improvement in the preservation of retinal morphology and chemical composition.

Functional Morphology of the Lipid Layer of the Tear Film.

Meibomian glands secrete the oily layer of the tear film, which prevents excessive evaporation of tear fluid. Dysfunction of meibomian glands is not only one of the causes of evaporative dry eye but also one of the main causes of entire dry eye. To understand the pathophysiology of meibomian gland dysfunction, it is important to evaluate both the morphology and function of the meibomian gland. We previously reported that meibography enabled visualization of the morphology of the meibomian gland. Meanwhile, tear interferometry was introduced as an evaluation method for the function of the meibomian gland. We combined observations of the oily layer and the aqueous layer of the tear film and found that a tear film compensatory system may work toward maintenance of tear film homeostasis. In this review, we describe both morphological evaluation systems for the meibomian gland, including noninvasive meibography, and functional evaluation systems, including tear interferometry. We further describe the morphological changes of the meibomian glands in various ocular surface diseases. Finally, we demonstrate the concept of a tear film compensatory system and propose a method for tear film component-oriented diagnosis.

New insights into the morphology and function of meibomian glands.

Meibomian glands secrete meibum, which gives rise to the lipid layer of the tear film and thereby prevents excessive evaporation of tear fluid. Meibomian gland dysfunction (MGD) is a major causative condition of evaporative dry eye, which is more common than the aqueous-deficient type of dry eye. Noninvasive meibography relies on infrared light and an infrared-sensitive camera to reveal the morphology of meibomian glands in both the upper and lower eyelids, whereas tear interferometry allows both qualitative and quantitative evaluation of the lipid layer of the tear film. These two techniques not only provide valuable clinical information related to dry eye but also allow clinical evaluation of MGD. Tear interferometry also has the potential to distinguish the condition of the tear film between normal individuals and dry eye patients. Furthermore, combined evaluation of the noninvasive breakup time of the tear film and the interferometric fringe pattern as determined by tear interferometry allows classification of the subtype of dry eye disease.

Promotion of Corneal Epithelial Wound Healing in Diabetic Rats by the Fibronectin-Derived Peptide PHSRN.

PURPOSE: Topical application of the fibronectin-derived peptide PHSRN facilitates corneal epithelial wound healing in healthy animals and in patients with nonhealing epithelial defects. We have now examined the effect of PHSRN eye drops on the healing of corneal epithelial wounds in diabetic rats. METHODS: Wistar rats were injected intraperitoneally with streptozotocin to induce diabetes or with a vehicle as a control. Four weeks after confirmation of the corresponding presence or absence of glycosuria, a 3-mm-diameter portion of the corneal epithelium of the right eye was excised and eye drops containing PHSRN (200 µM) or phosphate-buffered saline (PBS) vehicle were administered to the injured eye every 6 hours. RESULTS: The area of the epithelial defect did not differ significantly among the 4 experimental groups (diabetic or nondiabetic rats treated with PHSRN or vehicle) at 12 hours after wounding. At 18 hours, however, the area of the defect in diabetic rats treated with PHSRN (0.50 ± 0.34 mm) was significantly (P < 0.05) smaller than that in diabetic rats treated with PBS (1.06 ± 0.42 mm) and was similar to that in nondiabetic rats treated with PBS (0.60 ± 0.23 mm). The decrease in the size of the epithelial defect in diabetic rats treated with PHSRN was also found to be dependent on the dose of the peptide. CONCLUSIONS: Administration of PHSRN significantly facilitated healing of corneal epithelial wounds in diabetic rats, which suggests that PHSRN eye drops warrant further investigation as a treatment option for patients with diabetic keratopathy.

Changes in meibomian gland morphology and ocular higher-order aberrations in eyes with chalazion.

PURPOSE: To examine the changes in meibomian gland morphology and ocular higher-order aberrations (HOAs) in eyes with chalazion and its excision. METHODS: Seven male patients with previous history of chalazion excision and seven control male subjects were enrolled. Changes in meibomian gland morphology (meiboscores, gland dropout, and shortening) were evaluated by using meibography equipped in a wavefront analyzer KR-1W and in a slit-lamp device BG-4M. Ocular HOAs were measured sequentially with KR-1W. The tear film breakup time (BUT) was measured. RESULTS: Both KR-1W and BG-4M visualized meibomian gland as clear similar images. The tear film BUT (mean ± SD, 5.6±3.0 vs 9.4±2.3 seconds, P=0.025), the total meiboscore (median [interquartile range], 2 (2-3) vs 0 (0-1), P=0.007) as well as the meibomian gland dropout rate (86% vs 14%, P=0.008) and shortening rate (100% vs 29%, P=0.031) differed significantly between the patient and control groups. The first total ocular HOAs (0.142±0.063 vs 0.130±0.015, P=0.80) were similar in both groups, whereas the stability index of the total HOAs over time (0.0041±0.0048 vs -0.0012±0.0020, P=0.030) differed significantly between the patient and control groups. CONCLUSIONS: Chalazion and its excision were associated with dropout and shortening rate of meibomian glands. The morphological changes of meibomian glands in chalazion may be associated to instability of the tear film, which was suggested by the tear film BUT and the stability of ocular HOAs.

Morphology and Function of Meibomian Glands and Other Tear Film Parameters in Junior High School Students.

PURPOSE: We measured tear film parameters, including the morphology and function of meibomian glands, in junior high school students at 15 years of age. METHODS: A total of 111 eyes of 111 students (56 males and 55 females) were enrolled in the study. The ocular symptom score (0-14), after-school study time, lipid layer thickness (LLT) of the tear film, partial blink rate, lid margin abnormalities (0-4), tear film breakup time, corneal and conjunctival epithelial damage (fluorescein staining score, 0-9), meiboscore as determined by noncontact meibography (0-6), Schirmer test value, and meibum grade (0-3) were determined. The relationships between parameters were evaluated with the Spearman correlation coefficient (ρ). RESULTS: The meiboscore was 2.8 ± 1.2, and the meibum grade was 1.8 ± 1.2. The meiboscore significantly correlated with the meibum grade (ρ = 0.272, P = 0.004), Schirmer test value (ρ = -0.220, P = 0.021), and LLT (ρ = -0.264, P = 0.005). The breakup time significantly correlated with LLT (ρ = 0.261, P = 0.006), meibum grade (ρ = -0.338, P < 0.001), and fluorescein staining score (ρ = -0.214, P = 0.025). The partial blink rate significantly correlated with the Schirmer test value (ρ = -0.240, P = 0.011). The meiboscore (P < 0.001) and meibum grade (P = 0.032) were significantly greater in males than in females. CONCLUSIONS: The morphology and function of meibomian glands are altered even at 15 years of age, with the changes being more prominent in males than in females.

Effects of a warm compress containing menthol on the tear film in healthy subjects and dry eye patients.

Menthol is thought to stimulate lacrimation via activation of cold-sensitive primary afferent neurons in the cornea. We evaluated a warm compress containing menthol as a potential treatment for dry eye by examining its effects on the tear film in healthy subjects (n = 20) and dry eye patients (n = 35). Disposable eyelid-warming steamers that either did (MH) or did not (HO) contain menthol were applied to one eye of each subject either once only for 10 min or repeatedly over 2 weeks. Single application of MH significantly increased tear meniscus volume (P = 8.6 × 10-5, P = 1.3 × 10-5) and tear film breakup time (P = 0.006, P = 0.002) as well as improved meibum condition in healthy subjects and dry eye patients, respectively. Repeated application of MH significantly increased tear meniscus volume (P = 0.004, P = 1.7 × 10-4) and tear film breakup time (P = 0.037, P = 0.010) in healthy subjects and dry eye patients, respectively. Repeated application of MH thus induced persistent increases in tear fluid volume and tear film stability in dry eye patients, suggesting that repeated use of a warm compress containing menthol is a potential novel treatment for dry eye disease.