Addressing excessive evaporation: an unmet need in dry eye disease.

Dry eye disease (DED) is a common condition in which tear film abnormalities result in a damaging cycle of tear hyperosmolarity, desiccating stress, inflammation, and ocular surface injury. In a healthy tear film, meibum produced by the meibomian glands forms a lipid layer that stabilizes the tear film and protects against aqueous tear evaporation. Excessive tear evaporation due to a deficient lipid layer is believed to be the most common cause of DED, and most evaporative DED is associated with meibomian gland dysfunction (MGD); this highlights the pathophysiologic importance of the dysfunctional tear lipid layer. Current treatments for DED may be used to supplement hyperosmolar aqueous tears, lubricate the ocular surface, increase meibum flow, decrease inflammation, promote tear production, or otherwise decrease clinical signs of ocular surface damage and/or improve symptoms. Until now, no prescription eye drop has directly addressed the excessive evaporation that occurs in most patients with DED. Perfluorohexyloctane (PFHO) ophthalmic solution (MIEBO™; Bausch + Lomb) is a preservative-free eye drop that has demonstrated the ability to form a long-lasting barrier that inhibits evaporation in preclinical studies. FDA approval of PFHO was based on results from 2 pivotal clinical trials (GOBI [NCT04139798] and MOJAVE [NCT04567329]) in patients with DED and clinical signs of MGD which demonstrated consistent improvements in both signs and symptoms of disease, with a safety profile similar to that of saline eye drops. PFHO is the first and only FDA-approved eye drop that directly targets tear evaporation in patients with DED, thereby promoting ocular surface healing and providing symptomatic relief.

The effect of pregnancy on meibomian gland, tear film, cornea and anterior segment parameters.

AIM: In this prospective study, we aimed to examine the effect of physiological and pathological changes that occur during pregnancy in regard to Meibomian Gland (MG) structure, tear film, cornea and anterior segment parameters. METHODS: The following groups were compared: 49 eyes of 49 pregnant women at 16-20 weeks of pregnancy (P16 Group), 46 eyes of 46 pregnant women at 32-36 weeks of pregnancy (P32 Group) and 51 eyes of 51 participants who were not pregnant (P0 Group). The groups were compared in terms of the first break-up time (NIF-BUT) and average break-up time (NIAvg-BUT) values. Non-contact meibography and MG loss rates were also compared. RESULTS: The groups were found to be compatible in terms of age (P=0.052). The mean NIF-BUT values in the P16, P32 and P0 groups were 4.7 ±2.7, 6 ±3 and 6.7 ±3.1 seconds, respectively (P=0.055). The mean MG loss rates for the upper lid in the P16, P32 and P0 groups were 35.3%±12.6, 33.4%±11.4 and 15.5%±5.4, respectively. The loss rates for the lower lid in the P16, P32 and P0 groups were found to be 40.5%±18.6, 40.5%± 14.4 and 20.1%±8.1, respectively (P=0.000, p=0.000). The mean anterior chamber value (ACV) was found in the P16, P32 and P0 groups with 160.8 ±31.8, 150.9 ±26.5 and 165.9 ±26.5 µm3, respectively (P=0.035). CONCLUSION: MG loss was found to be higher in pregnant groups compared to the non-pregnant groups. We found minimal instability in the tear film of the pregnant groups. We believe that pregnant women should be followed closely in terms of ocular surface diseases.

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

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

Comparative of meibomian gland morphology in patients with evaporative dry eye disease versus non-dry eye disease.

Many recent studies have showed that morphological changes are one of the key signs of meibomian gland disease (MGD). These changes can be seen even before symptom onset, potentially underestimating the prevalence of MGD; however, until now, there is no conclusive information about the impact of meibomian gland (MG) morphology in tear film physiology and disease. This study aimed to investigate the prevalence of anatomical and morphological MG alterations between patients with evaporative dry eye disease (DED) and healthy controls. Retrospective chart review of seventy-five patients with evaporative DED and healthy individuals who had dry eye assessments included Ocular Surface Disease Index questionnaire, meibum quality, meibum expressibility, lid margin abnormality, ocular staining, non-invasive tear film break-up time, and meibography. We did not find significant differences in MG alterations in the upper lid between healthy and DED subjects. Patients with evaporative DED presented MG alterations in the lower lid more frequently than healthy subjects (54.8 vs. 30.3%; p = 0.03). The presence of shortened glands was the only MG alteration that was more prevalent in the lower lid in dry-eye patients than in healthy subjects (p < 0.05). Subjects with evaporative DED presented more alterations in the lower lid than healthy subjects.

Lacritin proteoforms prevent tear film collapse and maintain epithelial homeostasis.

Lipids in complex, protein-enriched films at air/liquid interfaces reduce surface tension. In the absence of this benefit, the light refracting and immunoprotective tear film on eyes would collapse. Premature collapse, coupled with chronic inflammation compromising visual acuity, is a hallmark of dry eye disease affecting 7 to 10% of individuals worldwide. Although collapse seems independent of mutation (unlike newborn lung alveoli), selective proteome and possible lipidome changes have been noted. These include elevated tissue transglutaminase and consequent inactivation through C-terminal cross-linking of the tear mitogen lacritin, leading to significant loss of lacritin monomer. Lacritin monomer restores homeostasis via autophagy and mitochondrial fusion and promotes basal tearing. Here, we discover that lacritin monomer C-terminal processing, inclusive of cysteine, serine, and metalloproteinase activity, generates cationic amphipathic α-helical proteoforms. Such proteoforms (using synthetic peptide surrogates) act like alveolar surfactant proteins to rapidly bind and stabilize the tear lipid layer. Immunodepletion of C- but not N-terminal proteoforms nor intact lacritin, from normal human tears promotes loss of stability akin to human dry eye tears. Stability of these and dry eye tears is rescuable with C- but not N-terminal proteoforms. Repeated topical application in rabbits reveals a proteoform turnover time of 7 to 33 h with gradual loss from human tear lipid that retains bioactivity without further processing. Thus, the processed C-terminus of lacritin that is deficient or absent in dry eye tears appears to play a key role in preventing tear film collapse and as a natural slow release mechanism that restores epithelial homeostasis.

Effect of warming eyelids on tear film stability and quality of life in visual display terminal users: a randomized controlled trial.

We aimed to evaluate the effect of warming eyelids on tear-film stability and quality of life (QoL) in video display terminal (VDT) users. A prospective study was conducted and 45 volunteers with ocular symptoms and tear-film instability associated with VDT use were randomly allocated into the study (n = 22) or control groups (n = 23). Subjects in the study group used eyelid warming steamer (EWS) for 2 weeks and tear fluorescein breakup time (TBUT) after single and 2-week EWS treatment, Schirmer I test, ocular surface staining scores, meibomian gland assessment, severity of dry eye disease (DED) and QoL scores after 2-week EWS treatment were analysed. The TBUT improved after both single and 2-week EWS treatment (P = 0.023 and 0.027, respectively) in the study group. The ocular surface staining scores were significantly decreased only in the study group (P = 0.038). About 60% DED patients in the study group shifted towards non-DED and the pattern of distribution was significantly different compared to baseline (P < 0.001). The QoL scores significantly improved in the study group (P = 0.002) with a negative correlation with TBUT. In conclusion, in VDT users with short TBUT, eyelid warming steamer is effective in improving tear-film stability and QoL.

Comparative Analysis of Age-Related Changes in Lacrimal Glands and Meibomian Glands of a C57BL/6 Male Mouse Model.

It is not known how biological changes in the lacrimal (LGs) and meibomian (MGs) glands contribute to dry eye disease (DED) in a time-dependent manner. In this study, we investigated time-sequenced changes in the inflammation, oxidative stress, and senescence of stem cells in both glands of an aging-related DED mouse model. Eight-week (8W)-, one-year (1Y)-, and two-year (2Y)-old C57BL/6 male mice were used. MG areas of the upper and lower eyelids were analyzed by transillumination meibography imaging. The number of CD45+, 8-OHdG+, Ki-67+, and BrdU+ cells was compared in both glands. Increased corneal staining and decreased tear secretion were observed in aged mice. The MG dropout area increased with aging, and the age-adjusted MG area in lower lids was negatively correlated with the National Eye Institute (NEI) score. Increased CD4+ interferon (IFN)-γ+ cells in LGs were found in both aged mice. An increase in 8-OHdG+ cells in both glands was evident in 2Y-old mice. Reduced Ki-67+ cells, but no change in CD45+ cells, was observed in the MGs of 1Y-old mice. Increased BrdU+ cells were observed in the LGs of aged mice. This suggests that age-dependent DED in C57BL/6 mice is related to inflammation of the LGs, the development of MG atrophy, and oxidative stress in both glands.

Not All Dry Eye in Contact Lens Wear Is Contact Lens-Induced.

OBJECTIVES: To compare subjective and clinical outcomes in three study groups: (1) asymptomatic contact lens (CL) wearers (ASYM); (2) symptomatic CL wearers who become asymptomatic on lens removal; and (3) symptomatic CL wearers who do not resolve on lens removal. METHODS: Ninety-two subjects completed the Berkeley Dry Eye Flow Chart with and without lenses, ocular surface examinations, and a battery of questionnaires. RESULTS: Thirty-seven subjects (40%) were ASYM, 30 (33%) had contact lens-induced dry eye (CLIDE), and 25 (27%) had underlying physiological DE. Visual Analog Scale ratings, OSDI score, and SPEED score were significantly better for the ASYM group (P<0.001) but did not distinguish CLIDE from DE. The DE group was significantly worse than CLIDE and ASYM, which were similar, in precorneal noninvasive tear breakup time (8.2 sec DE vs. 12.3 sec CLIDE and 14.3 sec ASYM; P=0.002), anterior displacement of the Line of Marx (P=0.017), and superior conjunctival staining (P=0.001). CONCLUSIONS: Many CL wearers presenting with dryness symptoms have an underlying DE condition and will not respond to treatments aimed at changing lenses or solutions. Contradictory results from research studies of DE in CL wearers could be due in part to a failure to distinguish subjects with symptoms due specifically to CL wear from those whose symptoms have underlying causes unrelated to CL wear.

Tear Film and Meibomian Gland Characteristics in Adolescents.

PURPOSE: To establish normative values of ocular surface parameters in adolescents and explore factors associated with meibomian gland (MG) dropout. METHODS: Subjects between 8 and 17 years of age were enrolled in this cross-sectional study. All subjects were given dry eye and lifestyle questionnaires. Tear film assessments and meibography were performed. Statistical tests included a one-way analysis of variance to test differences in ocular surface parameters between age groups and linear correlations between clinical findings and lifestyle factors. RESULTS: Two hundred twenty-five subjects completed the study. Thirty-four subjects (15%) reported ocular discomfort, primarily itching. Tear meniscus height increased with age and was greatest in the oldest subjects (mean = 0.25 mm, P < 0.01). Across all subjects, meibography showed that 39% of the upper and 39% of the lower eyelids had MG dropout. The average MG dropout score was 0.50 ± 0.57 for the upper eyelids and was 0.67 ± 0.93 for the lower eyelids. There was no correlation between phone/tablet usage and MG dropout for either the upper (P = 0.39) or lower (P = 0.56) eyelids. CONCLUSIONS: The frequency of ocular symptoms in these adolescents was 15%. Because MG dropout is thought to increase with age, it was unexpected to observe that most subjects in this study had mild MG dropout in 1 or both eyelids. Although electronic device usage did not correlate with MG dropout in this study sample, it is still unclear what the effects of long-term digital device usage may have as the subjects age.

Meibomian Gland Morphology: The Influence of Structural Variations on Gland Function and Ocular Surface Parameters.

PURPOSE: To objectively and quantitatively characterize meibomian gland morphology and to investigate the influence of morphological variations on gland function and ocular surface and tear film parameters. METHODS: One hundred fifty subjects were enrolled. The examinations included tear osmolarity, tear meniscus height, bulbar conjunctival hyperemia, noninvasive tear film breakup time, lid margin thickness, foam secretion, meibomian gland expressibility, count of functioning glands, corneal and conjunctival staining, fluorescein breakup time, lid wiper epitheliopathy, and Schirmer test. Patient symptoms were assessed using the Ocular Surface Disease Index questionnaire. Images from noncontact meibography were analyzed using an automated method that objectively estimates dropout area, number of glands, gland length and width, and gland irregularity. RESULTS: Gland irregularity highly correlated with dropout area (r = -0.4, P < 0.001) and showed significant partial correlations with fluorescein breakup time (r = 0.162, P = 0.049) and the Ocular Surface Disease Index questionnaire (r = -0.250, P = 0.002) Subjects with dropout area <32% were divided into 2 groups: high and low irregularity. Gland expressibility was statistically significantly different between the 2 groups (U = 319.5, P = 0.006). In the high irregularity group, gland irregularity correlated with the Schirmer test (r = 0.530, P = 0.001) and corneal fluorescein staining (r = -0.377, P = 0.021). CONCLUSIONS: Automated morphological analysis of meibomian gland structure provides additional quantitative and objective information regarding gland morphology. The link between dropout area and gland function is not clear. Assessment of gland irregularity might better predict gland function and its effects on ocular surface and tear film parameters.

Ectodysplasin-A signaling is a key integrator in the lacrimal gland-cornea feedback loop.

A lack of ectodysplasin-A (Eda) signaling leads to dry eye symptoms, which have so far only been associated with altered Meibomian glands. Here, we used loss-of-function (Eda-/-) mutant mice to unravel the impact of Eda signaling on lacrimal gland formation, maturation and subsequent physiological function. Our study demonstrates that Eda activity is dispensable during lacrimal gland embryonic development. However, using a transcriptomic approach, we show that the Eda pathway is necessary for proper cell terminal differentiation in lacrimal gland epithelium and correlated with modified expression of secreted factors commonly found in the tear film. Finally, we discovered that lacrimal glands present a bilateral reduction of Eda signaling activity in response to unilateral corneal injury. This observation hints towards a role for the Eda pathway in controlling the switch from basal to reflex tears, to support corneal wound healing. Collectively, our data suggest a crucial implication of Eda signaling in the cornea-lacrimal gland feedback loop, both in physiological and pathophysiological conditions. Our findings demonstrate that Eda downstream targets could help alleviate dry eye symptoms.

Tear film analysis and evaluation of optical quality: A review of the literature.

Dry eye is a complex multifactorial disease of the ocular surface and tears. It is associated with ocular surface symptoms and is one of the most common causes for ophthalmologic consultation. Despite their frequent use in clinical practice, the usual tests to evaluate dry eye and ocular surface disease-history of symptoms, tear break-up time (TBUT), Meibomian gland evaluation, corneal fluorescein staining, Schirmer test-have shown low reproducibility and reliability. In addition, subjective symptoms are often weakly or poorly correlated with objective signs. Since the tear film is the first system through which light must pass, the optical quality of the eye is highly dependent on the homogeneity of the tear film. Various investigative methods have been developed to evaluate both the structural and functional quality of the tear film, such as corneal topography, interferometry, tear meniscus measurement, evaporation rate, tear osmolarity and even aberrometry. Some are easily accessible to clinicians, while others remain in the field of clinical research. All of these tests provide a better understanding of the pathophysiology of the tear film. This review hopes to provide an overview of the existing tests and their role in evaluating the significance of the tear film in visual function.

Investigating the subjective cooling effect of eyelid cleansing gel on eyelid and ocular surface temperature.

PURPOSE: To investigate if the application of Blephagel, an eyelid cleansing gel, causes subjective and/or objective cooling effects by measuring ocular symptomology and temperature. METHODS: Twenty-five healthy subjects underwent baseline non-invasive temperature measurements on the closed upper eyelid (centrally, nasally, and temporally) and ocular surface temperature (OST) on both eyes using an infrared camera. A standard application of Blephagel was then applied to the closed upper eyelid and eyelashes with a sterile cotton-wool to one eye selected at random. Temperature measures were then repeated on both eyes after 30-60, 120-150, and 180-210 s. At each interval, subjects rated the comfort and any cooling sensation of each eye on a 0-10 scale. RESULTS: After application of the gel, there was a significant difference in temperature at all locations on the eyelid between the test and control eyes over time (F = 9.322, p < 0.001). Post hoc analysis revealed this was significant from 30 to 60 s interval (36.3 ± 1.1 °C versus 37.2 ± 0.7 °C; p < 0.001) and the 120-150 s interval (36.8 ± 0.8 °C versus 37.2 ± 0.6 °C; p < 0.001). There was no significant variation between the OST locations over time (F = 3.350, p = 0.07). With respect to symptoms, there was a significant increase in cooling sensation in the test eye compared to the control eye over time (F = 10.438, p < 0.001), that remained throughout the experiment. CONCLUSIONS: Blephagel produces a reduction in temperature of the eyelids that is accompanied with a subjective cooling sensation.

The function and morphology of Meibomian glands in patients with thyroid eye disease: a preliminary study.

BACKGROUND: To investigate function and morphology of the meibomian gland (MG) in patients with thyroid eye disease (TED). METHODS: In this prospective case series study, patients with unilateral or bilateral TED were consecutively enrolled. The diagnosis of TED was based on the typical orbital findings and/or radiographic evidence. The disease activity of TED was classified according to the clinical activity score (CAS). Degrees of lagophthalmos and exophthalmos, blinking rates, and results of the Schirmer test 1 were also recorded. All patients completed the SPEED questionnaire and underwent MG assessment, including lipid layer thickness (LLT), MG dropout (MGd), and MG expression. RESULTS: In total 31 eyes from 17 patients with unilateral or bilateral TED were included. Patients were divided into inactive TED (CAS 0-1; 20 eyes from 11 patients) and active TED (CAS 2-3, 11 eyes from 6 patients) groups. MGd was significantly more severe in the active TED than the inactive TED group [Median (Inter-quartile region): 3.0 (2.0-3.0) vs. 2.0 (1.0-2.0) degree, P = 0.04]. However, patients with active TED had thicker LLT than those with inactive TED (90.0 [80.0-100.0] vs. 65.0 [47.8-82.5] nm, P = 0.02), and LLT was positively correlated with lagophthalmos (r = 0.37, P = 0.04). CONCLUSIONS: Patients with active TED had more severe MGd, but thicker LLT. Active TED may cause periglandular inflammation of MGs, leading to MGd, but compensatory secretion from residual MGs and lagophthalmos-induced forceful blinking might temporarily release more lipids over the tear film.

The significance of meibomian gland changes in asymptomatic children.

PURPOSE: To evaluate meibomian gland morphology and function in children without ocular discomfort. METHOD: A total of 266 eyes of 266 children without signs or symptoms of ocular surface dysfunction were enrolled. Morphology of meibomian glands (MG) and non-invasive break-up time (BUT) was assessed by noncontact meibography. Based on lipid layer thickness (LLT) of the tear film measurements, 66 children were chosen to be assessed by meibomian glands yielding liquid secretion (MGYLS). RESULTS: Based on the presence of physiologic conjunctival follicles (PCF), participants were divided into normal or PCF groups. The distortion and deficiency of MG function was significantly higher in PCF group (P = 0.002, 0.007, respectively). Five different gland duct shapes (vertical, tortuous, overriding, hooked, U-shaped) were observed. MG deficiency was positively correlated with age (R = 0.362, P < 0.001). Distortion and the number of MG showed no correlation with age (P > 0.05). However, distortion and deficiency of MG were negatively correlated with LLT (P < 0.001, P < 0.01). CONCLUSION: Children with PCF had significantly more MG distortion and deficiency which was associated with LLT. These results prompt future studies to determine if changes in MG morphology are congenital or acquired.

The correct diagnosis and therapeutic management of tear dysfunction: recommendations of the P.I.C.A.S.S.O. board.

PURPOSE: To describe a standard approach to manage tear dysfunction (TD), in order to obtain a clinically favourable outcome. TD is a highly prevalent, yet largely underdiagnosed, condition that affects from 5 to 30% of the population above 50 years old. Left untreated, TD is associated with eye discomfort and ocular surface disease, substantially affecting quality of life. Although the prevalence of this problem is increasing significantly, a standard approach to its prevention and treatment is not available yet. METHODS: In September 2015, a team of Ocular Surface Italian Experts convened for a roundtable to discuss on the latest knowledge about diagnosis and treatments for TD and the real issues in the management of these patients. The discussion centred on the appropriate definition of TD, proposing a new classification of risk factors and how to identify them, how to make a correct diagnosis choosing the rational therapy (questionnaires, symptoms' time relation, seasonality, low tech diagnostic manoeuvres, specific tests for the detection of tear film disturbances leading to recognition of the level of disease and of the ocular system elements involved), which artificial tear matches the ideal profile for a rational therapy and which questions should be done to the patient. RESULTS: A multi-item flowchart for tear film dysfunction, with point-by-point explanatory guide, to better identify and manage the patient with this disorder is provided. CONCLUSIONS: The growing prevalence of TD demands increased attention. An appropriate prevention and a treatment pattern for the patient, combined with greater patient-practitioner interaction, and patient education is offered.

Function of meibomian gland: Contribution of proteins.

The meibomian gland is the major contributor to the tear film lipid layer. It is generally accepted that meibomian gland secretions, i.e, meibum, play a critical role in the homeostasis of the tear film. Lipid components of meibum and their structure, as well as functions were intensively studied. However, the proteins from meibum have not attracted enough attention. This review summarizes current knowledge about protein components of the meibum, particularly their function on tear film and ocular surface, and changes in the proteins during meibomian gland dysfunction (MGD).

Role of EGF receptor signaling on morphogenesis of eyelid and meibomian glands.

The epidermal growth factor receptor (EGFR) signaling has a pivotal role in the regulation of morphogenesis during development and maintenance of homeostasis in adult eyelid and its adnexa. Studies have demonstrated that during eyelid morphogenesis the EGFR signaling pathway is responsible for keratinocyte and mesenchymal cell proliferation and migration at the eyelid tip. For meibomian gland morphogenesis, EGFR signaling activation stimulates meibomian gland epithelial cell proliferation. EGFR signaling pathway functions through multiple downstream signals such as ERK, Rho/ROCK and integrin and is regulated by a variety of upstream signals including Adam17, GPR48 and FGFR signaling. Herein we review the literature that describe the role of EGFR and its related signaling pathways in eyelid and meibomian gland morphogenesis.

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.

[Analysis of structure and function of meibomian glands in healthy population at different ages].

Objective: To observe the structure and function of meibomian glands in normal population at different ages. Methods: From October 2011 to August 2012, meibomian gland information was collected in healthy volunteers without any symptoms of ocular discomfort, aged more than 5 years. The people were grouped by every 10 years of age. The meibomian gland opening, secretion state and characteristics and Max's line were observed by slit lamp microscopic examination, and the meibomian gland dropouts were examined by noncontact infrared meibomian gland microscopy. The changes of meibomian glands were scored from 0 to 3, 0 for a normal state, 1 for mild abnormality, 2 for moderate abnormality and 3 for severe abnormality. The Mann-Whitney U test was used to compare the meibomian scores between male and female, and between left and right eyes. The correlation of these scores and the age of volunteers was analyzed by the Spearman test. Results: Among all the 100 volunteers, there were 47 males and 53 females, aged from 5 to 83 years (mean, 40.9±22.9). The meibomian gland dropouts were gradually increasing with age, significantly faster after 40 years old (scores for each age group were 2(1), 2(1), 2(1), 2(1), 3(2), 3.5(1.75), 4(3), 6(2). Meibomian gland opening, secretion traits and secretor status gradually became poorer with age, and changes were dramatically fast in the group of 40-49 years of age [scores of this group were 3(1.5), 3(3) and 2(2)], but slowed down after age of 50 years. Moreover, the Max's line position moved to the front gradually with age, with a marked change in the group of 40-49 years of age [scores for each age group were 0(1), 1(1), 2(2), 2(2), 3(2), 2(2), 3(2)], 4 gland changes showed a significantly positive relation to age(r=0.729, 0.635, 0.669, 0.639, 0.470. P<0.01), but not to gender and eye dominance (P>0.05). Conclusions: Meibomian gland opening and meibomian gland secretion become worse with age. The age of 50 years old is the key period for the meibomian gland changes. (Chin J Ophthalmol, 2017, 53: 528-533).