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.

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.

Histopathologic changes associated with Meibomian Gland dropout in a dog.

PURPOSE: To perform histopathologic analysis of tissue manifesting meibomian gland dropout on noncontact infrared meibography in a dog. METHODS: A 14-year-old intact male Cairn terrier was evaluated at Triangle Animal Eye Clinic for dense corneal opacity of the right eye. A complete ocular examination was performed, including slit-lamp biomicroscopy, tonometry, and noncontact meibography. Pigmentary glaucoma with elevation of intraocular pressure was diagnosed, and meibography revealed morphological changes suggestive of gland dropout in the middle of the upper right eyelid. RESULTS: The globe was enucleated by the transpalpebral method, and palpebral tissue was subjected to histopathologic analysis. The analysis revealed an almost complete loss of meibomian gland structure accompanied by slight enlargement and proliferation of fibroblasts as well as by infiltration of plasma cells and lymphocytes. CONCLUSIONS: Meibomian gland dropout as detected by meibography can be associated with chronic inflammation.

Assessment of meibomian gland morphology by noncontact infrared meibography in Shih Tzu dogs with or without keratoconjunctivitis sicca.

OBJECTIVE: To investigate meibomian gland (MG) morphology by noncontact infrared meibography in Shih Tzu dogs with or without keratoconjunctivitis sicca (KCS). PROCEDURES: Fourteen eyes of 12 Shih Tzu dogs (mean age of 10.7 years, range of 7-13 years) presented to Yakumo Animal Hospital or Triangle Animal Eye Clinic from 2011 to 2017 with clinical signs and a Schirmer tear test (STT) result consistent with KCS (<10 mm/min) were examined. Twenty-eight eyes of 16 Shih Tzu dogs (mean age of 12.4 years, range of 8 to 15 years) with a STT > 15 mm/min served as healthy controls. Both groups of dogs underwent routine slitlamp biomicroscopy followed by noncontact infrared meibography of the upper eyelid with both desktop-type and mobile-type systems. Results Meibography revealed morphological abnormalities of MGs in 13 eyes of 11 dogs with KCS. The abnormalities included gland shortening in 64% and gland dropout in 64% of the 14 eyes in the KCS group. Morphological changes were also observed in MGs of 16 eyes of 10 dogs in the control group. These changes included shortening in 46% and dropout in 17.8% of the 28 eyes in the control group. Dropout was significantly more common in eyes with KCS than in control eyes (P < 0.01). Conclusions The frequency of MG abnormalities is increased in Shih Tzus with KCS compared with control animals. A reduced quality of the tear film associated with increased evaporation and reduced retention of tear fluid likely exacerbates the effects of a reduced tear volume in animals with aqueous deficiency.

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.

Ocular surface inflammation impairs structure and function of meibomian gland.

Dysfunction of the meibomian glands alters secreted meibum quantitatively and qualitatively that can lead to damage to the ocular surface epithelium. In response to an unstable tear film cause by meibomian gland dysfunction, ocular surface epithelium is damaged and expresses inflammatory cytokines leading to secondary ocular inflammation. In turn, inflammatory disorders of the palpebral conjunctiva and lid margin may affect the structure and function of meibomian gland. The disorders include allergic conjunctivitis, long-term usage of contact lenses, dermatological diseases that affect conjunctival homeostasis, Stevens-Johnson's syndrome or chemical burning of the ocular surface and lid margin.

Clinical safety and efficacy of vitamin D3 analog ointment for treatment of obstructive meibomian gland dysfunction.

BACKGROUND: Hyperkeratinization is a major cause of obstructive meibomian gland dysfunction (oMGD) and results in degenerative gland dilation and atrophy without inflammation. Ointment containing 1,25-dihydroxy-22-oxavitamin D3 (maxacalcitol), a noncalcemic analog of the active form of vitamin D3, is applied for the treatment of hyperkeratotic cutaneous conditions such as psoriasis and ichtyosis because it suppresses the proliferation and promotes the differentiation of keratinocytes through interaction with the vitamin D receptor. The aim of the present study was to evaluate the safety and efficacy of maxacalcitol ointment for the treatment of oMGD. METHODS: Six eyes of six healthy male subjects (mean age ± SD, 36.4 ± 10.8 years) and 12 eyes of eight oMGD patients (five men and three women; mean age ± SD, 55.6 ± 13.2 years) were enrolled in the study. Maxacalcitol ointment was applied to the upper and lower lid margins twice a day for 8 weeks. Subjective symptoms, lid margin abnormalities, tear film breakup time (BUT), ocular surface staining, meibum grade, Schirmer test value, and meibomian gland area were evaluated in the oMGD patients before, during, and after the treatment period. RESULTS: Severe adverse effects of ointment application were not observed in the healthy subjects or oMGD patients. The clinical scores for plugging of meibomian gland orifices and lid margin vascularity as well as BUT, meibum grade, and meibomian gland area were significantly improved in oMGD patients after the 8-week treatment period compared with pretreatment values (P values of <0.001, 0.020, 0.030, 0.020, and 0.017, respectively). CONCLUSIONS: Topical eyelid application of an analog of the active form of vitamin D3 was found to be safe as well as to improve the condition of patients with oMGD. Such ointment thus warrants further evaluation as a potential new treatment option for this condition. TRIAL REGISTRATION: This study was registered with the UMIN database (ID: UMIN000016230 ) on 16 January 2015.

New Insights Into the Lipid Layer of the Tear Film and Meibomian Glands.

Meibomian glands secrete lipids (meibum) that form the surface lipid layer of the tear film and thereby prevent excessive evaporation of tear fluid. Meibomian gland dysfunction is a major cause of evaporative dry eye, which is more prevalent than aqueous-deficient dry eye. Noninvasive meibography with infrared light and an infrared charge-coupled device camera can detect morphological changes of meibomian glands in both upper and lower eyelids, whereas tear interferometry allows qualitative and quantitative evaluations of the lipid layer of the tear film. Such assessment of meibomian gland morphology provides clinical information that contributes to the diagnosis of evaporative dry eye, whereas that of the lipid layer of the tear film allows the monitoring of meibomian gland function. In addition, the balance between the lipid and aqueous layers of the tear film revealed by tear interferometry has provided both support for the operation of a compensatory system that maintains tear film homeostasis as well as insight into the pathophysiology of dry eye.

Meibomian Gland Dysfunction and Contact Lens Discomfort.

Meibomian glands are located in the eyelids and secrete meibum, which gives rise to the lipid layer of the tear film. Changes to these glands can lead to the development of meibomian gland dysfunction (MGD), which is associated with various ocular symptoms such as fatigue, dryness, burning sensation, and heavy sensation. The diagnosis of MGD thus relies on evaluation of ocular symptoms, meibum condition, and lid margin abnormalities. The recent development of noninvasive meibography and tear interferometry has provided important insight into meibomian gland structure and function, respectively. Wearers of contact lenses complain of ocular symptoms that are thought to be attributable to a variety of causes, such as a diminished aqueous or mucin layer of the tear film, changes in tear protein concentration, and altered meibomian gland structure or function. Many studies have examined the relation between contact lens wear and meibomian gland changes. Such studies have found that lens wear is associated with adverse changes in meibomian gland morphology and in the condition of the lid margin and meibum, suggesting that contact lenses negatively affect meibomian glands. Meibomian gland dysfunction-like changes in meibomian glands induced by contact lens wear may thus be responsible for at least some of the ocular symptoms in lens wearers.

Linoleic acid content of human meibum is associated with telangiectasia and plugging of gland orifices in meibomian gland dysfunction.

To examine the relation between changes in the free fatty acid (FFA) composition of human meibum and both objective signs and subjective symptoms of meibomian gland dysfunction (MGD), we analyzed the FFA content of meibum collected from both MGD patients and control subjects. Thirty-eight patients with MGD (13 men and 25 women; mean age ± SD, 66.9 ± 15.0 years) were evaluated. Various objective signs and subjective symptoms of MGD were assessed. Meibum was analyzed by liquid chromatography-Fourier transform mass spectrometry, and the relation between the FFA composition of meibum and each objective sign and subjective symptom was examined by principal component analysis (PCA). No relation was apparent between the FFA composition of meibum and individual subjective symptoms or objective signs of MGD. However, a PCA score plot for meibum samples grouped on the basis of the severity of both telangiectasia and plugging of meibomian gland orifices revealed clear separation of mild and severe groups. This separation of the two groups was largely due to a significantly increased linoleic acid content in meibum of the severe group (3.56%, versus 0.70% of total FFAs in the mild group). The relative amount of linoleic acid in meibum was thus associated with the severity of telangiectasia and plugging of gland orifices in MGD, suggesting that this FFA might contribute to the pathogenesis of these signs.

Morphological changes in the meibomian glands of patients with phlyctenular keratitis: a multicenter cross-sectional study.

BACKGROUND: Phlyctenular keratitis is a hypersensitivity reaction of the cornea, and a complication of eyelid margin disease in children and young adults. In this study, we compared the morphology of the meibomian glands in eyelids between phlyctenular keratitis patients and healthy young adults, using noncontact meibography. METHODS: The study included 16 eyes of 13 patients diagnosed with phlyctenular keratitis and 17 eyes of 17 healthy volunteers. Slit-lamp observations of the cornea and eyelid were performed on all subjects. The morphology of the meibomian glands was scored using non-contact meibography (meiboscore). The meiboscore in worse eye was used in bilateral phlyctenular keratitis. RESULTS: All eyes with phlyctenular keratitis, but not normal controls, showed corneal nodules, neovascularization, and superficial punctate keratopathy. The mean meiboscore in phlyctenular keratitis patients (upper lid: 2.9 ± 0.3, lower lid: 2.7 ± 0.5) was significantly higher than in controls (upper lid: 0.4 ± 0.6, lower lid: 0.1 ± 0.3). CONCLUSIONS: Noncontact meibography enabled visualization of meibomian gland loss in phlyctenular keratitis patients, suggesting a relationship between abnormalities of the meibomian glands in young individuals and the pathogenesis of phlyctenular keratitis.

Increased Tear Fluid Production as a Compensatory Response to Meibomian Gland Loss: A Multicenter Cross-sectional Study.

PURPOSE: To compare tear film parameters as well as meibomian gland morphologic features and function among patients with meibomian gland dysfunction (MGD), those with non-Sjögren syndrome aqueous-deficient dry eye (non-SS ADDE), those with non-SS ADDE and MGD, and normal subjects. DESIGN: Multicenter, cross-sectional, observational case series. PARTICIPANTS: Forty-one eyes of 41 patients (all women; mean age ± standard deviation, 62.1±9.9 years) with non-SS ADDE, 70 eyes of 70 patients (all women; 66.0±8.7 years) with MGD, 17 eyes of 17 patients (all women; 72.4±7.8 years) with non-SS ADDE and MGD, and 70 eyes of 70 normal control subjects (all women; 65.0±7.1 years). METHODS: Ocular symptoms were scored from 0 to 14 and lid margin abnormalities from 0 to 4 according to their respective number. Meibomian gland changes were scored from 0 to 6 (meiboscore) on the basis of noncontact meibography findings, and meibum was graded from 0 to 3 depending on its volume and quality. Conjunctival and corneal epithelial damage were scored from 0 to 9 (fluorescein score). Tear film break-up time (TBUT) was measured as an index of tear film stability, and tear fluid production was evaluated with Schirmer's test. MAIN OUTCOME MEASURES: Ocular symptom score, lid margin abnormality score, meiboscore, meibum grade, fluorescein score, TBUT, and Schirmer's test value. RESULTS: The ocular symptom score did not differ significantly between the MGD and non-SS ADDE groups (P = 0.762). The lid margin abnormality score, meiboscore, and meibum grade were significantly higher in the MGD group than in the non-SS ADDE group (P = 0.0012, P < 0.0001, and P < 0.0001, respectively). The fluorescein score, TBUT, and Schirmer's test value were significantly worse in the non-SS ADDE group than in the MGD group (P < 0.0001, P = 0.0061, and P < 0.0001, respectively). The meiboscore correlated significantly with Schirmer's test value only in the MGD group (ρ = 0.508, P = 8.3×10(-6)). CONCLUSIONS: An increase in tear fluid production likely compensates for loss of meibomian glands in individuals with MGD.

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.

Comparison of Intense Pulsed Light Treatments including Upper Lid or Lateral Canthus in Patients of Meibomian Gland Dysfunction.

Background: To determine the differences in the effects of intense pulsed light (IPL) treatment when including the upper and lower lid or lateral canthus area in patients with meibomian gland dysfunction (MGD). Methods: Patients who underwent three IPL treatment sessions at 3-week intervals were divided into three groups according to the treatment sites: group A, lower lid; group B, upper and lower lids; and group C, lower lid and lateral canthal area. Before and after the IPL treatment sessions, we obtained the lid abnormality score (LAS), meibum expressibility (ME), meibum quality (MQ), lipid layer thickness (LLT), type I Schirmer test (ST), tear break-up time (TBUT) test, corneal fluorescein staining scores (CFSs), and Ocular Surface Disease Index (OSDI). Results: IPL treatment significantly improved LASs, ME, MQ, TBUT, CFS, and OSDI values in all groups. Differences in LAS values before and after IPL treatment were significantly greater in groups B and C than those in group A. Conclusions: IPL treatment encompassing the upper lid and lateral canthus together with the lower lid elicited additional improvement in patients with MGD. The additional effect on treating the lateral canthus was similar to the effect observed on the additional treatment of the upper lid.

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.

Caffeine increases tear volume depending on polymorphisms within the adenosine A2a receptor gene and cytochrome P450 1A2.

PURPOSE: The primary aim of the present study was to examine the effect of caffeine on tear volume. The secondary aim was to investigate the relation between caffeine-induced changes in tear volume and polymorphisms in ADORA2A and CYP1A2. DESIGN: Double-masked, placebo-controlled, crossover study. PARTICIPANTS: Seventy-eight healthy volunteers were recruited for the study. METHODS: Subjects participated in 2 sessions in which they received capsules containing either placebo or caffeine. The caffeine capsules were given to the subjects to keep the caffeine volume per body weight within 5 to 7 mg/kg. After caffeine intake, tear meniscus height (TMH) was measured. Subjects provided a blood sample for genotyping. MAIN OUTCOME MEASURES: Tear meniscus height, single nucleotide polymorphism. RESULTS: The tear volume increased after caffeine consumption. The net increase in TMH was 0.08 mm (95% confidence interval, 0.05-0.10) greater when participants were given caffeine than when given placebo (P<0.0001). In ADORA2A, the difference in the net increase in TMH for participants who were heterozygous at rs5751876 and rs2298383 was 0.07 mm (P = 0.001) and who were minor homozygous was 0.08 mm (P = 0.007). In CYP1A2, the net increase in TMH for participants who were minor homozygous at rs2472304 was lower than for those who were major homozygous; the difference was 0.06 mm (P = 0.039). CONCLUSIONS: Caffeine intake increases tear volume and polymorphisms within ADORA2A, and CYP1A2 is associated with the tear increase after caffeine intake. Genetic polymorphisms had a significant effect on tear meniscus that was of limited clinical significance.

Effects of long-term topical anti-glaucoma medications on meibomian glands.

OBJECTIVE: To examine effects of long-term topical anti-glaucoma medications on meibomian gland morphology and function and assess their relationship with slit-lamp findings. METHODS: This was a cross-sectional observational case series of 31 patients with glaucoma (mean age ± standard deviation, 65.0 ± 13.0 years; mean duration of eye drop use, 7.9 ± 6.0 years) treated with topical anti-glaucoma drugs in only one eye for more than 1 year: 13 receiving prostaglandin analogues (PGs) alone, eight receiving ß-blockers alone, and ten receiving multiple treatments. Untreated contralateral eyes served as controls. Lid margin (lid margin abnormality score: 0-4) and superficial punctate keratopathy (SPK score: 0-1) were observed with a slit lamp. Upper and lower eyelids were turned over to observe meibomian glands using non-contact meibography. Meibomian gland loss was scored for each eyelid from grade 0 (no loss of meibomian glands) through grade 3 (loss >2/3 of total meibomian gland area). Meibomian lipid content (meibum) was scored (meibum score: 0-3). RESULTS: Treated eyes had significantly higher scores for lid margin abnormality (P= 0.001), SPK (P< 0.001), meibo-score (P< 0.001), and meibum (P< 0.001) than control eyes. Tear film break-up time (BUT) was significantly shorter in treated eyes than in control eyes (P= 0.001). Schirmer values were significantly lower in treated eyes than in control eyes (P= 0.0039). Subgroup analysis indicated a significantly higher meibo-score in eyes treated with PGs (P= 0.0046) and in eyes treated with ß-blockers (P= 0.0231) than in the corresponding controls. CONCLUSIONS: Long-term anti-glaucoma eye drop use affects meibomian gland morphology and function.

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.