Effects of a Long-Acting Diquafosol Ophthalmic Solution on the Ocular Surface, Tolerability, and Usability in Dry Eye Disease.

INTRODUCTION: This study aimed to investigate the tolerability of high-viscosity diquafosol tetrasodium (DQS) ophthalmic solution (DIQUAS LX; DQSLX) and examine its usability and effect on clinical findings in patients with dry eye disease (DED). METHODS: This interventional retrospective study included 66 eyes of 66 patients with DED who switched from conventional DQS to DQSLX ophthalmic solution. Tear function assessments (tear film breakup time [BUT], keratoconjunctival vital staining [VS] score), evaluations of DED symptom relief, and a four-item usability questionnaire ("comfort upon instillation," "irritation upon instillation," "eye mucus discharge," "convenience of instillation frequency") assessed using a visual analog scale from 0 (worst) to 10 (best) were administered 4 weeks after switching to DQSLX. Factors associated with drug tolerability were assessed using multiple regression analysis. RESULTS: The symptoms improved by 64.2% after switching to DQSLX. The BUT value, VS score, and the questionnaire items "comfort upon instillation" and "convenience of instillation frequency" were significantly improved after switching to DQSLX. DQSLX tolerability was reported as acceptable in 56 (84.8%) and unacceptable in 10 (15.2%) patients. Overall, DQSLX tolerability was significantly associated with "comfort upon instillation" and "convenience of instillation frequency" and tended to be associated with a VS score ≥ 1. DQSLX tolerability depended on symptom and VS score improvements and absence of excessive "eye mucus discharge" in patients with a VS score ≥ 1 (39 patients), but on "comfort upon instillation" and absence of excessive "eye mucus discharge" in patients with a VS score = 0 (27 patients). CONCLUSION: The high-viscosity DQSLX ophthalmic solution was generally considered acceptable in the study population. However, drug tolerability seemingly differed between patients with DED with and without epithelial damage. The former were affected by improvements in symptoms and clinical findings, whereas the latter were affected by comfort upon instillation. TRIAL REGISTRATION: University Hospital Medical Information Network identifier, UMIN000051390.

Electroencephalogram-detected stress levels in the frontal lobe region of patients with dry eye.

PURPOSE: To evaluate stress levels extracted from prefrontal electroencephalogram (EEG) signals and investigate their relationship with dry eye symptoms. METHODS: This prospective, cross-sectional, comparative study included 25 eyes of 25 patients with aqueous tear-deficient dry eye (low Schirmer group), 25 eyes of 25 patients with short tear breakup time dry eye (short breakup time group), and 24 eyes of 24 individuals without dry eye. An EEG test, the Japanese version of the Ocular Surface Disease Index (OSDI), and a stress questionnaire were administered. EEG-detected stress levels were assessed under three conditions: eyes closed, eyes open, and eyes open under ocular surface anesthesia. RESULTS: Stress levels were significantly lower when the eyes were closed than when they were open in all groups (all P < 0.05). Stress levels during eyes open under ocular surface anesthesia were significantly lower than those during eyes open without anesthesia only in the low Schirmer group; no differences were found between the short breakup time and control groups. OSDI scores were associated with EEG-detected stress levels (P = 0.06) and vital staining score (P < 0.05) in the low Schirmer group; they were not associated with EEG-detected stress (P > 0.05), but with subjective stress questionnaire scores and breakup time values in the short breakup time group (P < 0.05). CONCLUSIONS: In the low Schirmer group, peripheral nerve stimulation caused by ocular surface damage induced stress reactions in the frontal lobe, resulting in dry eye symptoms. Conversely, in the short breakup time group, the stress response in the frontal lobe was not related to symptom development.

Autonomic Nerve Activity Features According to Dry Eye Type.

Purpose: The purpose of this study was to investigate the association between autonomic nerve activity and symptom intensity according to the type of dry eye (DE). Methods: This prospective, cross-sectional, comparative study included 25 eyes of 25 patients with short tear break-up time DE (sBUTDE; mean age = 57.4 ± 11.4 years, range = 30-74 years) and 24 eyes of 24 patients with aqueous tear-deficient DE (ADDE; mean age = 62.3 ± 10.7 years, range = 29-76 years) were studied. Autonomic nerve activity was examined, and the Japanese version of the Ocular Surface Disease Index (J-OSDI) and a stress check questionnaire were administered. Autonomic nerve activity was continuously measured for 10 minutes. The parameters were low-frequency (LF) and high-frequency (HF) components of heart rate variability, reflecting cardiac sympathetic and parasympathetic nerve activity, and parasympathetic nerve activity alone, respectively; and the coefficient of variation of R wave-to-R wave (RR) interval (cvRR), component coefficient of variation of LF (ccvLF), and component coefficient of variation of HF (ccvHF), reflecting fluctuation of RR interval, LF, and HF, respectively. Results: Higher J-OSDI scores were associated with higher HF, ccvHF, and subjective stress in sBUTDE, showing a significant correlation (r = 0.53, P < 0.01; r = 0.55, P = 0.01; and r = -0.66, P = 0.01); no correlations were observed between the J-OSDI score and autonomic parameters and stress in ADDE. Conclusions: DE symptoms were significantly associated with the magnitude and fluctuation of parasympathetic activity in sBUTDE. Thus, among the autonomic parameters, parasympathetic activity is involved in the development of symptoms in sBUTDE, whereas the involvement of the autonomic nervous system may be minimal in ADDE.

TFOS Lifestyle: Impact of nutrition on the ocular surface.

Nutrients, required by human bodies to perform life-sustaining functions, are obtained from the diet. They are broadly classified into macronutrients (carbohydrates, lipids, and proteins), micronutrients (vitamins and minerals) and water. All nutrients serve as a source of energy, provide structural support to the body and/or regulate the chemical processes of the body. Food and drinks also consist of non-nutrients that may be beneficial (e.g., antioxidants) or harmful (e.g., dyes or preservatives added to processed foods) to the body and the ocular surface. There is also a complex interplay between systemic disorders and an individual's nutritional status. Changes in the gut microbiome may lead to alterations at the ocular surface. Poor nutrition may exacerbate select systemic conditions. Similarly, certain systemic conditions may affect the uptake, processing and distribution of nutrients by the body. These disorders may lead to deficiencies in micro- and macro-nutrients that are important in maintaining ocular surface health. Medications used to treat these conditions may also cause ocular surface changes. The prevalence of nutrition-related chronic diseases is climbing worldwide. This report sought to review the evidence supporting the impact of nutrition on the ocular surface, either directly or as a consequence of the chronic diseases that result. To address a key question, a systematic review investigated the effects of intentional food restriction on ocular surface health; of the 25 included studies, most investigated Ramadan fasting (56%), followed by bariatric surgery (16%), anorexia nervosa (16%), but none were judged to be of high quality, with no randomized-controlled trials.

Variability of autonomic nerve activity in dry eye with decreased tear stability.

The autonomic nervous system plays a crucial role in the maintenance of homeostasis. Neurogenic inflammation due to decreased stability of tear film may induce changes in autonomic nerve activity, which could be associated with symptom expression.This study aimed to measure biological parameters that represent autonomic nerve activity in dry eye (DE)s caused by tear film dysfunction and investigate their relationship with symptom intensity. This prospective, cross-sectional, comparative study evaluated 34 eyes of 34 participants (mean age: 52.5 ± 13.4 years; range: 20-81 years) without keratoconjunctival damage. Nineteen eyes in the DE group showed DE symptoms and tear break-up time (TBUT) of ≤5 seconds (short TBUT DE); the 15 eyes in the non-DE group showed no DE symptoms. Autonomic nerve activity was measured for 10 minutes-starting and ending 5 minutes before and after instilling ophthalmic solution-and evaluated using the low-frequency component (LF) to the high-frequency component (HF) ratio of heart rate variability (autonomic balance). The pre-ophthalmic solution administration LF/HF ratio was not significantly different (P = 0.59) between the two groups, however, the standard deviation of the LF/HF ratio (LF/HF-SD) tended to be higher in the DE group than that in the non-DE group (P = 0.086). The DE symptom intensity was significantly related to LF/HF-SD (P = 0.005), which significantly decreased after ophthalmic solution administration in the DE group (P = 0.04). The large fluctuations in autonomic balance may be key for the understanding of the mechanism underlying DE symptoms.

Therapeutic Efficacy and Safety of Intense Pulsed Light for Refractive Multiple Recurrent Chalazia.

To evaluate the efficacy and safety of intense pulsed light (IPL) combined with meibomian gland expression (MGX) for the treatment of refractory multiple and recurrent chalazia without surgery or curettage. This was a retrospective controlled study. Patients with multiple and recurrent chalazia, who had performed the conventional treatment at least 2 months without any surgery or curettage, were enrolled in this study. Twenty-nine consecutive multiple recurrent chalazia (12 patients) were assigned to receive either the combination of IPL and MGX or MGX alone as a control. Each eye underwent one to four treatment sessions with 2-week intervals. Parameters were evaluated before and 1 month after the final treatment session. Clinical assessments included symptom, size of each chalazion, lid margin abnormalities, corneal and conjunctival fluorescein staining, meibum grade, the number of Demodex mites, the Schirmer value and meiboscore. All parameters except meiboscore and the Schirmer value were significantly improved with IPL-MGX therapy, whereas only meibum grade was significantly improved with MGX alone. There were no adverse events which occurred in either group. IPL-MGX was safe and effective for multiple and recurrent chalazia without surgery or curettage by reducing the size of chalazion and improving lid margin abnormalities and meibum grade.

Topical glaucoma medications - Clinical implications for the ocular surface.

Glaucoma is a leading cause of irreversible blindness. The use of topical eye drops to reduce intraocular pressure remains the mainstay treatment. These eye drops frequently contain preservatives designed to ensure sterility of the compound. A growing number of clinical and experimental studies report the detrimental effects of not only these preservatives but also the active pharmaceutical compounds on the ocular surface, with resultant tear film instability and dry eye disease. Herein, we critically appraise the published literature exploring the effects of preservatives and pharmaceutical compounds on the ocular surface.

Comparison of Intense Pulsed Light Therapy on Patients with Meibomian Gland Dysfunction Using AQUA CEL and M22 Devices.

The purpose of this study was to compare the efficacy of Intense Pulsed Light (IPL) therapy for meibomian gland dysfunction (MGD) using the new AQUA CEL (AC, Jeisys) device and the traditional M22 (Lumenis) device. A total of 59 eyes of 59 patients with MGD (12 men and 47 women, mean age 49 ± 12 years) were enrolled. They randomly received four sessions of IPL therapy every three weeks either with AC (30 eyes) or M22 (29 eyes). Standard Patient Evaluation of Eye Dryness (SPEED) questionnaire score, noninvasive breakup time (NIBUT), lid margin abnormalities, corneal and conjunctival fluorescein staining, fluorescein breakup time (FBUT), Schirmer's test, meiboscore and meibum grade were evaluated before treatment and one month after treatment. Before IPL, no significant differences were seen in age, gender, or measured parameters between the AC and M22 groups (p > 0.05, respectively). SPEED score, NIBUT, lid margin abnormalities, fluorescein staining, FBUT, and meibum grade improved significantly in both groups after IPL compared to before IPL (p < 0.001, respectively). There were no significant differences in measured parameters between the two groups after IPL (p > 0.05, respectively). IPL therapy with AC and M22 devices has been shown to be equally effective for the treatment of MGD.

Association of Serum Lipid Level with Meibum Biosynthesis and Meibomian Gland Dysfunction: A Review.

The primary role of meibomian glands (MGs) is to actively synthesize and secret lipids and proteins spread onto the tear film, and the glandular lipids promote tear stability, prevent evaporation, and reduce friction. Meibomian gland dysfunction (MGD) is the leading cause of dry eye disease and one of the most common ophthalmic problems worldwide. MGs are densely innervated and regulated by hormones and growth factors. However, since the polar and nonpolar lipids are produced through processes in MGs that are not completely understood, a relevant question has been raised: Would the altered systemic lipids metabolism affect the physiology and structure of MGs? This review introduces the recent update regarding the relationships between serum lipid and MGD in clinical and basic research while providing answers to this question. A causal relationship remains to be established; however, serum lipid level or dyslipidemia may be related to MGD directly or indirectly, or both. Further studies are warranted to establish the role of serum lipid level and meibocyte differentiation/maturation and lipid synthesis.

Adverse Effects and Safety in Glaucoma Patients: Agreement on Clinical Trial Outcomes for Reports on Eye Drops (ASGARD)-A Delphi Consensus Statement.

PURPOSE: The purpose of this study is to establish consensus among experts on outcomes and methods to be used in clinical trials to assess adverse effects of anti-glaucomatous eye drops. DESIGN: Modified Delphi method. METHODS: Clinical experts from Europe, North America, South America, the Middle East, and Asia were invited to participate in 2 sequential web-based surveys administered from June 27 to August 29, 2021. A total of 91 clinical experts were invited to participate. Of these, 71 (78%) experts from 23 different countries accepted the invitation and answered the first questionnaire. The importance of items was ranked using a 10-point scale (1 as not important, 10 as very important). RESULTS: A total of 84 items were rated in round one by 71 participants. Of these, 68 (81%) reached consensus. In round 2, 19 items, including 3 additional items, were rated by 53 (75%) participants. Consensus was reached in 98% of investigated items. Eight outcomes were agreed as important to assess when conducting future trials: ocular surface, dryness, epithelial damage, local adverse effects related to eye drops as reported by patients, periocular surroundings and eyelids, quality of life questionnaires, hyperemia, visual acuity, tear film, and anterior chamber inflammation. CONCLUSION: We propose a consensus-based series of outcomes and assessment methods to be used in clinical trials assessing adverse effects of antiglaucomatous eye drops. This, we hope, will improve the comparability of results from future trials and thus facilitate meta-analyses and progress in this field.

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.

Relationship between serum lipid level and meibomian gland dysfunction subtype in Korea using propensity score matching.

To analyze the relationship between systemic lipid profile levels and meibomian gland dysfunction (MGD) subtype in Korea. The ophthalmic data of 95 eyes and the serum lipid profiles of 95 patients were reviewed. These factors were compared with those of the general population using data from the Korean National Health and Nutrition Examination Survey (KNHANES), which evaluated 2,917 subjects. Of these, the comparison group (1:5 ratio; n = 475) was selected using propensity score matching according to age and sex. In addition, we analyzed the relationship between serum lipid profile levels and MGD subtypes in MGD patients. The mean high-density lipoprotein (HDL) value of the MGD patients was significantly higher than that of the general population (P < 0.0001). Moreover, the mean low-density lipoprotein (LDL) levels of the MGD patients was significantly lower than that of the general population (P = 0.0002). However, the mean total cholesterol (TC), and triglyceride (TG) levels of the MGD patients were not significantly different from those of the general population (TC: P = 0.4282, TG: P = 0.5613). In addition, no serum lipid levels statistically differed among the MGD subtypes (TC: P = 0.7650, HDL: P = 0.2480, LDL: P = 0.3430, TG: P = 0.7030). A statistically significant increase in HDL and decrease in LDL concentration were observed in the MGD group, although there was no difference in any serum lipid level among the MGD subtypes.

Effects of Lipiflow Treatment Prior to Cataract Surgery: A Prospective, Randomized, Controlled Study.

To investigate the effects of preoperative Lipiflow (Johnson & Johnson, Jacksonville, FL, USA) treatment before cataract surgery on meibomian gland dysfunction (MGD) and dry eye induced by surgery. DESIGN: Prospective, randomized controlled study. METHODS: This study comprised 124 eyes of 124 patients with planned surgery for senile cataract. Participants were randomly allocated into control and Lipiflow groups based on administration of Lipiflow treatment 3 weeks before cataract surgery. For meibomian gland (MG) evaluation, MG atrophy, degree of gland expressibility, and quality of gland secretions were examined at the baseline visit and 1 and 3 months postoperatively. Ocular surface parameters of tear film break-up time, Oxford corneal staining score, and tear film lipid layer thickness were measured at each visit. Ocular Surface Disease Index and Dry Eye Questionnaire were also assessed. RESULTS: The control group exhibited a significant decrease in MG expressibility, worsened meibum quality, decreased lipid layer thickness, and worsened corneal staining after cataract surgery. Also, dry eye symptom showed significant worsening. Conversely, the Lipiflow group showed significantly improved MG patency and meibum quality, increased tear film break-up time, and reduced corneal staining, and presented improved subjective outcomes reported on both Ocular Surface Disease Index and Dry Eye Questionnaire. The improvement of each parameter in the Lipiflow group showed a linear correlation with baseline MGD grade. In addition, patients without baseline MGD showed less worsening or improvement of MGD and dry eye induced by surgery, with preoperative Lipiflow treatment. CONCLUSIONS: Preoperative Lipiflow treatment conducted before cataract surgery may be a safe and effective intervention for relieving MGD and dry eye induced by surgery. It might be recommended not only for the patients with preoperative MGD but also for those without baseline MGD, to prevent the development of MGD and dry eye induced by ocular surgeries.

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.

Morphological Changes of Meibomian Glands in Men With Benign Prostate Hyperplasia.

PURPOSE: Meibomian glands are subject to regulation by sex hormones. We have now investigated the possible relation between benign prostate hyperplasia (BPH) and meibomian gland dysfunction (MGD). METHODS: Men diagnosed with BPH and receiving treatment with tamsulosin and age-matched male control subjects who attended Itoh Clinic, Saitama, Japan, were enrolled. An ocular symptom score, lid margin abnormality score, and superficial punctate keratopathy score as well as the meiboscore (0-6), meibum grade, breakup time of the tear film, and Schirmer test values were evaluated. Male pattern baldness was also graded according to the Hamilton-Norwood scale. RESULTS: Forty-four eyes of 44 men with BPH (mean age ± SD, 76.1 ± 2.2 years) and 46 eyes of 46 control subjects (mean age ± SD, 75.3 ± 6.2 years) were enrolled. The meiboscore in the BPH group (4.5 ± 1.4) was significantly higher than that in the control group (1.8 ± 1.5, P < 0.0001). Breakup time of the tear film was significantly shorter (3.6 ± 1.7 vs. 5.6 ± 2.5 seconds, P < 0.0001), and Schirmer test value was significantly smaller (9.8 ± 4.8 vs. 13.3 ± 8.0 mm, P = 0.048) in the BPH group than that in the control group. Other ocular parameters did not differ significantly between the 2 groups. The proportion of men with androgenic alopecia was also higher in the BPH group than that in the control group. CONCLUSIONS: BPH was associated with meibomian gland loss and instability of the tear film as well as with the presence of androgenic alopecia.

Efficacy of Azithromycin Eyedrops for Individuals With Meibomian Gland Dysfunction-Associated Posterior Blepharitis.

PURPOSE: To examine the safety and efficacy of azithromycin eyedrops in Japanese individuals with meibomian gland dysfunction (MGD)-associated posterior blepharitis. METHODS: Individuals with MGD-associated posterior blepharitis who visited the Itoh Clinic, Saitama, Japan, were randomly assigned to receive azithromycin (1%) eyedrops (AZM group, 16 eyes of 16 patients) or preservative-free artificial tears (control group, 20 eyes of 20 patients) for 2 weeks. All subjects also applied a warming eyelid compress twice per day. Subjective symptoms (Standardized Patient Evaluation of Eye Dryness [SPEED] score), lipid layer thickness (LLT) and interferometric pattern of the tear film, plugging and vascularity of the lid margin, noninvasive break-up time of the tear film (NIBUT) and fluorescein-based break-up time of the tear film (TBUT), corneal-conjunctival fluorescein staining score, tear meniscus height, meibum grade, meiboscore, tear osmolarity, and Schirmer test value were determined before and after treatment. Side effects of treatment were also recorded. RESULTS: In the AZM group, SPEED score, LLT, interferometric pattern, plugging and vascularity of the lid margin, NIBUT, TBUT, meibum grade, and tear osmolarity were significantly improved after treatment compared with baseline. The SPEED score, interferometric pattern, plugging, vascularity, meibum grade, and tear osmolarity were also significantly improved after treatment in the AZM group compared with the control group. Common side effects in the AZM group were transient eye irritation and blurred vision. CONCLUSION: Azithromycin eyedrops improved eyelid inflammation, the quality and quantity of the lipid layer of the tear film, and tear film stability. Such eyedrops thus seem to be a safe and effective treatment for MGD-associated posterior blepharitis.

The role of meibography in ocular surface diagnostics: A review.

The meibomian glands are lipid-secreting glands located in the tarsal plates, whose secretory products cover the tear film, thereby reducing evaporation as well as ensuring lubrication of the ocular surface. The meibomian glands can be visualized at different levels of magnification by infrared meibography, laser confocal microscopy, and optical coherence tomography. These imaging modalities have been subject to much research and progress in clinical practice and have shaped our current understanding of meibomian glands in health and disease. In this review, we explore the evolution of meibography over the past decades, the major contributions of various meibographic modalities, and discuss their clinical significance.

Intraductal meibomian gland probing and its efficacy in the treatment of meibomian gland dysfunction.

Meibomian gland dysfunction (MGD) is a major cause of dry eye, affecting millions worldwide. Intraductal meibomian gland probing (MGP) aims to open obstructed meibomian glands using a small probe to promote meibum secretion. MGP has received increasing interest since 2010, and we critically evaluated the literature on the efficacy and safety of MGP. Despite positive results of MGP on dry eye symptoms in early single-group studies, MGP was not shown to consistently outperform controls in later controlled trials. Furthermore, MGP alone did not show improvement beyond placebo in the only placebo-controlled RCT conducted. Overall, the procedure appears safe. Self-limited intraoperative bleeding was frequent, but no major complications were reported. In conclusion, MGP has not yet been shown to be an effective treatment for MGD. Larger placebo-controlled trials need to be conducted to establish the potential effect of this novel treatment modality.

Punctate fluorescein staining scores in dogs with or without aqueous tear deficiency.

OBJECTIVE: To compare the superficial punctate fluorescein staining in dogs with and without aqueous tear deficiency. PROCEDURES: An eye from each client-owned dogs presented to Triangle Animal Eye Clinic between January and December 2018 underwent tear and ocular surface tests, which included the Schirmer tear test (STT), phenol red thread test (PRT), and strip meniscometry tube tear test (SMT). Punctate fluorescein staining of the cornea (PFS-C) and the upper palpebral conjunctiva (PFS-UPC) were also performed. Fifty-seven dogs with STT results of <15 mm/min had aqueous tear deficiency (AD); 31 dogs had <10 mm/min and 26 dogs had ≥10 mm/min. The 162 dogs with STT results of ≥15 mm/min did not have AD. The test results of the groups were compared using Kruskal-Wallis and Steel-Dwass multiple comparison tests. RESULTS: Two hundred and nineteen eyes from 219 dogs were enrolled in this study. The PRT and SMT results, presented as mean ± SD, were significantly lower in the AD group than in the non-AD group (PRT: 29.5 ± 8.1 vs 36.9 ± 5.6 mm/15 s; SMT: 6.2 ± 3.8 vs 10.8 ± 2.8 mm/5 s). The PFS scores were significantly higher in the AD group than in the non-AD group (PFS-C: 4.4 ± 0.7 and 3.7 ± 0.8; PFS-UPC: 2.3 ± 0.5 and 1.7 ± 0.5). CONCLUSIONS: These results suggest that aqueous tear deficiency is not only reflected by PRT and SMT but also PFS-C and PFS-UPC.