No full-text available
To read the full-text of this research,
you can request a copy directly from the authors.
Meibomian Gland Dysfunction: A Clinical Scheme for Description, Diagnosis, Classification, and Grading
Abstract
Although meibomian gland disease (MGD) is one of the most common disorders encountered in ophthalmic practice, there has been no descriptive system consistently accepted to clinically characterize the anatomical and correlative biochemical alterations that occur in this condition. The purpose of this review is to synthesize a clinical description of meibomian gland disease and to provide a scheme for diagnosis, classification, and quantification that will be of value in the clinical setting and in the conduct of clinical trials.
... The score was graded using the following grades: 0 = no loss of meibomian glands; 1 = meibomian gland loss involve less than 1/3 of the total meibomian gland area (33%); 2 = loss between 1/3 and 2/3 of the total meibomian gland area and 3 = loss of more than 2/3 of the total meibomian gland area. 16,17 Both the upper and lower eyelids were everted and the slit lamp was used to detect the meibomian gland dropout. The ultraviolet Burton lamp was used to grade the meibomian gland loss. ...
... It was also expressed as the percentage when the areas of meibomian gland loss were divided by the total area of the everted eyelid. The score of the upper and lower eyelids were then added to obtain the total meiboscore ranging from 0 to 6. 16,17 Stable pressure was applied on the central third of the lids and the number of glands with secretions were noted. The degree of ease in expressing meibomian secretion was graded on a scale from 0 to 3, where grade 0 = easy expression, 1 = mild expression, 2 = moderate, and 3 could not be expressed. ...
... The diagnostic sequence for assessment of MGD include patient questionnaire using subjective symptoms, TBUT, eyelid margin, and evaluation of MGD dropout (loss). 17 The participants' symptoms were assessed using the OSDI questionnaire. The results of this study showed that HIV and AIDS participants had significantly higher OSDI score when compared with the control group, P = 0.00. ...
Background: Meibomian gland dysfunction (MGD) is one of the most encountered diseases in the clinical practice but appears to be underappreciated as it does not cause blindness. Meibomian gland dysfunction is a multifactorial and complex disorder of the ocular surface.Aim: This study aims to evaluate the characteristics of the meibomian glands in individuals living with HIV and AIDS undergoing antiretroviral therapy.Setting: The study was conducted at the antiretroviral (ARV) clinic, Mankweng Hospital.Methods: This was a prospective study conducted with 37 HIV and AIDS participants and 20 healthy controls. All participants were assessed using the Ocular Surface Diseases Index (OSDI) score and, tear break-up time and lid margin regularity (using the slit-lamp biomicroscopy). The loss of the meibomian glands was evaluated using the Marx’s line. For this study, this line represented a clinical parameter of meibomian function.Results: The OSDI score was significantly higher in the HIV and AIDS group than that of the control participants (39.95 ± 18.65 and 13.00 ± 9.09, respectively, P 0.05). The tear breakup time (TBUT) for the HIV and AIDS study group was lower than that of the control group (7.95 ± 3.54 and 9.90 ± 3.70, respectively, P 0.05). The HIV and AIDS participants showed greater meibomian gland loss relative to the healthy controls (9.30 ± 4.97 and 5.70 ± 2.1, P 0.05).Conclusion: The loss of eyelid meibomian glands is common in people living with HIV and AIDS in comparison with healthy controls.Contribution: Although there is a decrease in sight-threatening complications in the era of ARVs, ocular surface disorders (OSD) are still commonly found, which may reduce the quality of life of HIV and AIDS individuals.
... (2) Assessment of upper or lower eyelid laxity as determined based on rotation (0 = 0-25%; 1 = 25-50%; 2 = 50-100%) and the snapback test (0 = prompt snapback; 1 = slow return; 2 = does not return fully until blinking) [24], respectively; (3) Inferior meibomian gland plugging graded on a scale from 0 to 3 (0 = none; 1 = less than 1/3; 2 = between 1/3 and 2/3; 3 = greater than 2/3 lid involvement, graded without contact) [25]; (4) Telangiectasias of the lower eyelids (0 = none; 1 = mild; 2 = moderate; 3 = severe) [25]; (5) Assessment of conjunctivochalasis (0 = absent vs. 1 = present) in each area of the lower eyelid (nasally, medially, and temporally); (6) Non-invasive tear film stability based on TBUT (5 µL of fluorescein placed, 3 measurements taken in each eye and averaged) [26]; (7) Fluorescein corneal staining graded according to the National Eye Institute (NEI) scale [26], with 5 areas of the cornea being assessed, including the inferior, nasal, superior, temporal, and central areas, and scored from 0 to 3 in each (max. total = 15); (8) Tear production graded based on mm wetting of anesthetized Schirmer's test placed in the inferior fornix for 5 min (300 s) [26]; (9) Meibum quality graded based on a scale from 0 to 4 (0 = clear; 1 = cloudy; 2 = granular; 3 = toothpaste; 4 = no meibum extracted) [25]; (10) Inferior eyelid meibomian gland dropout graded according to the Meiboscale (0 = no dropout; 1 ≤ 25% dropout; 3 = 25% to 75% dropout; 3 ≥ 75% dropout) [27]. ...
... (2) Assessment of upper or lower eyelid laxity as determined based on rotation (0 = 0-25%; 1 = 25-50%; 2 = 50-100%) and the snapback test (0 = prompt snapback; 1 = slow return; 2 = does not return fully until blinking) [24], respectively; (3) Inferior meibomian gland plugging graded on a scale from 0 to 3 (0 = none; 1 = less than 1/3; 2 = between 1/3 and 2/3; 3 = greater than 2/3 lid involvement, graded without contact) [25]; (4) Telangiectasias of the lower eyelids (0 = none; 1 = mild; 2 = moderate; 3 = severe) [25]; (5) Assessment of conjunctivochalasis (0 = absent vs. 1 = present) in each area of the lower eyelid (nasally, medially, and temporally); (6) Non-invasive tear film stability based on TBUT (5 µL of fluorescein placed, 3 measurements taken in each eye and averaged) [26]; (7) Fluorescein corneal staining graded according to the National Eye Institute (NEI) scale [26], with 5 areas of the cornea being assessed, including the inferior, nasal, superior, temporal, and central areas, and scored from 0 to 3 in each (max. total = 15); (8) Tear production graded based on mm wetting of anesthetized Schirmer's test placed in the inferior fornix for 5 min (300 s) [26]; (9) Meibum quality graded based on a scale from 0 to 4 (0 = clear; 1 = cloudy; 2 = granular; 3 = toothpaste; 4 = no meibum extracted) [25]; (10) Inferior eyelid meibomian gland dropout graded according to the Meiboscale (0 = no dropout; 1 ≤ 25% dropout; 3 = 25% to 75% dropout; 3 ≥ 75% dropout) [27]. ...
... (2) Assessment of upper or lower eyelid laxity as determined based on rotation (0 = 0-25%; 1 = 25-50%; 2 = 50-100%) and the snapback test (0 = prompt snapback; 1 = slow return; 2 = does not return fully until blinking) [24], respectively; (3) Inferior meibomian gland plugging graded on a scale from 0 to 3 (0 = none; 1 = less than 1/3; 2 = between 1/3 and 2/3; 3 = greater than 2/3 lid involvement, graded without contact) [25]; (4) Telangiectasias of the lower eyelids (0 = none; 1 = mild; 2 = moderate; 3 = severe) [25]; (5) Assessment of conjunctivochalasis (0 = absent vs. 1 = present) in each area of the lower eyelid (nasally, medially, and temporally); (6) Non-invasive tear film stability based on TBUT (5 µL of fluorescein placed, 3 measurements taken in each eye and averaged) [26]; (7) Fluorescein corneal staining graded according to the National Eye Institute (NEI) scale [26], with 5 areas of the cornea being assessed, including the inferior, nasal, superior, temporal, and central areas, and scored from 0 to 3 in each (max. total = 15); (8) Tear production graded based on mm wetting of anesthetized Schirmer's test placed in the inferior fornix for 5 min (300 s) [26]; (9) Meibum quality graded based on a scale from 0 to 4 (0 = clear; 1 = cloudy; 2 = granular; 3 = toothpaste; 4 = no meibum extracted) [25]; (10) Inferior eyelid meibomian gland dropout graded according to the Meiboscale (0 = no dropout; 1 ≤ 25% dropout; 3 = 25% to 75% dropout; 3 ≥ 75% dropout) [27]. Statistical Analysis: Statistical analyses were performed using the SPSS 28.0 (SPSS Inc, Chicago, IL, USA) statistical package. ...
Dry eye disease is an umbrella term that includes a variety of symptoms and signs. A link between diabetes mellitus and dry eye disease exists, but the associated phenotype needs further examination. Thus, our aim was to determine how diabetes mellitus relates to the dry eye disease phenotype. A prospective, cross-sectional study was conducted at the Miami Veteran Affairs Medical Center ophthalmology clinic between October 2013 and September 2019. Participants included a volunteer sample of 366 South Florida veterans with one or more symptoms or signs of dry eye disease [Dry Eye Questionnaire-5 ≥ 6 OR tear break-up time ≤ 5 OR Schirmer’s test score ≤ 5 OR corneal fluorescein staining ≥ 2]. Participants were divided into three groups: (1) individuals without diabetes mellitus (controls); (2) individuals with diabetes mellitus but without end-organ complications; and (3) individuals with diabetes mellitus and end-organ complications. Dry eye metrics were compared across groups. The main outcome measures included ocular symptom questionnaires [e.g., 5-item Dry Eye Questionnaire, Ocular Surface Disease Index, and ocular pain assessment] and clinical parameters obtained from an ocular surface evaluation. A total of 366 individuals were included (mean age 59 ± 6 years; 89% males; 39% White; 11% diabetes mellitus and end-organ complications; 15% diabetes mellitus but without end-organ complications). Individuals with diabetes mellitus and end-organ complications had lower symptom scores on the dry eye disease and pain-specific questionnaires compared to individuals with diabetes mellitus but without end-organ complications and controls (Ocular Surface Disease Index: 42.1 ± 24.5 vs. 38.9 ± 25.1 vs. 23.6 ± 16.2; p < 0.001; numerical rating scale of ocular pain intensity: 4.9 ± 3.2 vs. 4.3 ± 2.7 vs. 3.5 ± 2.7; p = 0.02). Eyelid laxity was also more severe in the group with diabetes mellitus and end-organ complications (0.69 ± 0.64 vs. 0.73 ± 0.72 vs. 1.08 ± 0.77; p = 0.004) compared to the two other groups. The diabetic dry eye disease phenotype is driven by signs more so than by symptoms, with anatomic eyelid abnormalities being more frequent in individuals with diabetes mellitus and end-organ complications. Given this, ocular surface abnormalities in individuals with DM may be missed if screened by symptoms alone. As such, individuals with DM should undergo a slit lamp examination for signs of ocular surface disease, including anatomic abnormalities.
... Introduction The existing reports on the definitions, classification, and severity of MGD are summarized (Table 3) [1,45,46,[94][95][96][97][98][99]. Clear definitions are only provided in the two reports from the Japanese MGD Working Group and the TFOS MGD International Workshop [1,45]. ...
... Classification Foulks et al. [94] published a detailed MGD classification in 2003 (Fig. 14). They classify MGD as a meibomian gland disease, and further classify it into low and high-delivery types. ...
... In the high-delivery MGD, there are subjective symptoms and abnormal findings around the orifice of the meibomian glands (vascularity, displacement of the MCJ, and irregular eyelid margins) similar to the low-delivery type; however, lipids expressed from the meibomian glands by eyelid compression are increased [46]. In addition to the characteristic eyelid findings, Foulks et al. [94] put forward the following characteristics: normal tear dynamics, various ocular surface disorders, absence of meibomian gland dropout, quantity of meibum ≥0.8 mm, with normal viscosity and evaporation rate. ...
... However in MGD, most commonly there is a low delivery status of meibo m to the ocular surface by meibom gland hyposecretion or obstruction. [3][4][5] The hyposecretion of meibum results in improper tear lipid layer which in turn increased the tear evaporation and make tear lm instability. [4][5][6] As a result MGD can lead to altered tear lm composition, ocular surface disease and ocular pain including foreign-body sensation, photophobia, and conjunctival injection. ...
... [3][4][5] The hyposecretion of meibum results in improper tear lipid layer which in turn increased the tear evaporation and make tear lm instability. [4][5][6] As a result MGD can lead to altered tear lm composition, ocular surface disease and ocular pain including foreign-body sensation, photophobia, and conjunctival injection. [4] MGD is one of the leading cause of evaporative dry eye disease in human. ...
... MGD patients show a reduction in casual oil level compared with normal subjects. [5,16] Several studies using meibometry are reported in dog and cats. They only reported the normal meibometry values. ...
Background
Meibomian gland dysfunction (MGD) is defined as functional abnormalities of the meibomian gland and is commonly caused by meibomian gland hyposecretion or obstruction. This results in an improper tear lipid layer which increases the tear evaporation and makes the tear film instability, leading to qualitative dry eye disease. In humans, a mainstay of the management of MGD is eyelid warming. This improves meibum secretion by melting pathologically altered meibomian lipids. While nearly ubiquitous in human medicine, there are no reports of the effects of warming therapy on the eyelids in veterinary medicine. This study is to evaluate the effect of warm compress therapy on canine tear film quality parameters. Eight systemically healthy male Beagle dogs with normal ophthalmic examinations (16 eyes) were used for this study. The temperature of the outer upper eyelid, the upper palpebral conjunctiva, and the central cornea were evaluated with an infrared thermometer, and tear film quality was assessed with meibometry and evaluation of the tear film break up time (TFBUT). These parameters were measured before and immediately following the application of the warm compress. A paired t-test was used to compare the data before and after warm compress treatment. For statistical analysis, SPSS was used and a P value < 0.05 was considered significant.
Results
All parameters increased after warm compression. The temperature of the outer and upper palpebral eyelid, and the central cornea increased significantly, from 34.0±1.0°C to 35.3±1.0°C, from 34.2±0.8°C to 35.5±0.8°C, from 34.2±0.8°C to 35.0±0.7°C, respectively. In meibometry, the mean±SD meibomian level at the baseline was 109.0±44.1 MU, whereas after warm compress therapy, it significantly increased to 155.9±71.3MU (p<0.05). TFBUT increased from 8.9±3.0 to 10.5±2.3 seconds.
Conclusions
Application of warm compress to the external eyelids has a significant effects of tear film quality parameters and may be useful to improve tear film stability in dogs.
... A score of 0 indicated clean meibum, 1 cloudy, 2 cloudy and grainy, and 3 thick, like toothpaste. 32 (ii) Evaluation of MG expression: Five middle region meibomian glands were scored from 0 to 3. A score of 0 means all glands were expressible, 1 means 3-4, 2 means 1-2, and 3 means none. We calculated the aggregate score from these eight glands' mean scores. ...
... We calculated the aggregate score from these eight glands' mean scores. 32 Double vital staining technique, as described by Arita et al, 33 was employed to evaluate the extent of injury to the conjunctival and corneal epithelium. Two microliters of a preservative-free mixture comprising 1% sodium fluorescein and 1% lissamine green were dropped into the conjunctival sac. ...
Purpose
The objective of this study was to assess the effectiveness of intense pulsed light (IPL) therapy in individuals diagnosed with glaucoma and dry eye disease (DED).
Methods
This randomized control study recruited 22 individuals diagnosed with glaucoma, ranging in age from 33 to 82 years. These participants were undergoing treatment with hypotensive eyedrops and had clinical indications and subjective complaints associated with dry eye. Each patient underwent three sessions of IPL therapy in one eye, while the contralateral eye served as the control eye (CT). The following parameters were assessed at three time points: baseline, week-2, and week-4. These parameters include non-invasive breakup time (NITBUT), tear meniscus height (TMH), conjunctivocorneal epithelial staining score (CS), tear film lipid layer (TFLL), meibomian gland expressibility score (MGEx), Schirmer I test, ocular bulbar redness score (OBRS), and ocular surface disease index (OSDI). Intraocular pressure (IOP), best-corrected visual acuity (BCVA), and corneal endothelial cell count (ECC) were assessed for safety. The clinical trial was registered on 25/12/2023 at ClinicalTrials.gov website (NCT06158984).
Results
Comparing baseline and 4-week measurements revealed that the IPL group found significant improvements in NITBUT (IPL: 8.74±2.60 sec. vs CT: 5.76±1.75 sec. p<0.01), TMH (IPL: 0.23±0.05mm vs CT: 0.19±0.06mm, p=0.011), C.S. (IPL: 1.14±0.56 vs CT: 1.95±1.17, p=0.005), TFLL (IPL: 2.91±2.91 vs CT:3.36±0.58, p=0.047), MGEx score (IPL: 1.14±0.35 vs CT: 1.45±0.51, p=0.020) and OSDI scores (IPL: 31.77±15.59 vs 50.59±21.55, p=0.002) significantly improved. Conversely, other parameters showed no significant improvements (p>0.05).
Conclusion
The progression of ocular surface disease in individuals using topical anti-glaucoma medication may worsen if the condition is not addressed. Nevertheless, IPL therapy has the potential to result in significant improvements in both objective and subjective measures of dry eye. Best-corrected visual acuity, endothelial cell count, and intraocular pressure were determined to be within the permitted limits. No adverse events were reported during the course of the study.
... Sebum is the secretion of SGs while meibum is the secretion of MGs; they both play a vital role in maintaining basic human biological activities [16][17][18][19]. Meibum seals the opposing lid margins during sleep, stabilizes the tear film, maintains a smooth optical surface for the cornea at the air-lipid interface, helps to spread the tear film on the ocular surface, reduces tear film evaporation, prevents spillover of tears from the lid margin, and prevents contamination of the tear film by sebum [14,16,19,20]. Sebum lubricates the skin and hair, makes them supple, and contributes significantly to the regulation of body temperature. ...
... Sebum lubricates the skin and hair, makes them supple, and contributes significantly to the regulation of body temperature. In addition, the secreted sebum protects the skin, creating the physiologically acidic skin environment, thus conditioning the skin flora and enabling the skin to be protected against pathogens [18,20]. To date, there are only a few studies that have described the localization of human eyelid biomarkers in detail by immunohistochemistry [21,22]. ...
Meibomian gland dysfunction (MGD) is one of the main causes of dry eye disease. To better understand the physiological functions of human meibomian glands (MGs), the present study compared MGs with free sebaceous glands (SGs) and hair-associated SGs of humans using morphological, immunohistochemical, and liquid chromatography—mass spectrometry (LCMS)-based lipidomic approaches. Eyelids with MGs, nostrils, lips, and external auditory canals with free SGs, and scalp with hair-associated SGs of body donors were probed with antibodies against cytokeratins (CK) 1, 8, 10, and 14, stem cell markers keratin 15 and N-cadherin, cell–cell contact markers desmoglein 1 (Dsg1), desmocollin 3 (Dsc3), desmoplakin (Dp), plakoglobin (Pg), and E-cadherin, and the tight junction protein claudin 5. In addition, Oil Red O staining (ORO) was performed in cryosections. Secretions of MGs as well as of SGs of nostrils, external auditory canals, and scalps were collected from healthy volunteers, analyzed by LCMS, and the data were processed using various multivariate statistical analysis approaches. Serial sections of MGs, free SGs, and hair-associated SGs were 3D reconstructed and compared. CK1 was expressed differently in hair-associated SGs than in MGs and other free SGs. The expression levels of CK8, CK10, and CK14 in MGs were different from those in hair-associated SGs and other free SGs. KRT15 was expressed differently in hair-associated SGs, whereas N-cadherin was expressed equally in all types of glands. The cell–cell contact markers Dsg1, Dp, Dsc3, Pg, and E-cadherin revealed no differences. ORO staining showed that lipids in MGs were more highly dispersed and had larger lipid droplets than lipids in other free SGs. Hair-associated SGs had a smaller number of lipid droplets. LCMS revealed that the lipid composition of meibum was distinctively different from that of the sebum of the nostrils, external auditory canals, and scalp. The 3D reconstructions of the different glands revealed different morphologies of the SGs compared with MGs which are by far the largest type of glands. In humans, MGs differ in their morphology and secretory composition and show major differences from free and hair-associated SGs. The composition of meibum differs significantly from that of sebum from free SGs and from hair-associated SGs. Therefore, the MG can be considered as a highly specialized type of holocrine gland that exhibits all the histological characteristics of SGs, but is significantly different from them in terms of morphology and lipid composition.
... Non-PL-MRKC is not accompanied with nodular-shaped cell infiltration and manifests keratoepitheliopathy [12,14]. It has been suggested that the pathogenesis of epitheliopathy is characterized by an unstable tear film due to free fatty acids resulting from bacterial lipolysis, evaporative dry eye accompanied with meibomian gland dysfunction, and possible direct epithelial damage due to fatty acids or bacterial exotoxins [12][13][14][15][16][17][18]. For the treatment of non-PL-MRKC, the use of antibiotics such as a cephem antibiotic, minocycline, and clarithromycin has previously been reported [14]; however, a standard treatment protocol has yet to be established. ...
... McCulley et al. [7] postulated that in their cases, the corneal epithelial damage described as SPK might have been due to tear film instability caused by fatty acid associated with bacterial lipolysis, or direct damage caused by fatty acids, rather than staphylococcal exotoxin [21][22][23]. In addition, since meibomitis is often associated with meibomian gland dysfunction, lipids secreted by the meibomian glands are thought to function in the tear film to retard evaporation from the aqueous layer of the tear film, and it was thought that obstructive meibomian gland dysfunction could result in evaporative dry eye [17,18]. The findings in a study by Suzuki et al. [12] indicated that SPK in non-PL-MRKC might be caused by bacterial exotoxin or damaged by altered lipids [12], and tear film instability caused by fatty acid associated with bacterial lipolysis, or direct damage caused by fatty acids as described by McCulley, and accompanied with evaporative dry eye [14]. ...
Meibomitis-related keratoconjunctivitis (MRKC) is characterized by meibomitis with corneal epithelial abnormalities, and can be divided into two types: MRKC accompanied with phlyctenular keratitis, and MRKC accompanied with keratoepitheliopathy that is similar to superficial punctate keratopathy (SPK). The purpose of this retrospective study was to investigate the characteristic features of keratoepitheliopathy and treatment outcomes for MRKC. This study involved 27 eyes of 18 MRKC patients (3 males and 15 females). National Eye Institute (NEI) scores and visual acuity were compared at pre and post treatment. All subjects were treated with a small-dose administration of clarithromycin. Keratoepitheliopathy characteristic to MRKC, yet different in appearance from SPK, was noted in 24 of the 27 eyes. Fluorescein staining revealed granular epithelial lesions generally larger than SPK that coexisted with small dark spots. In 17 eyes, keratoepitheliopathy was located within the pupillary zone, and the visual acuity in 12 eyes was less than 1.0. Our findings showed significant improvement in the NEI score in MRKC (p < 0.0001) and in visual acuity (p = 0.0157) post treatment, and the characteristic features of keratoepitheliopathy in MRKC that are often associated with decreased visual acuity were elucidated. The treatment of clarithromycin was found to be effective for MRKC with keratoepitheliopathy.
... Importantly, clinical studies have linked obstruction of the meibomian glands to meibomian gland dysfunction (MGD) leading to signs and symptoms of dry eye disease; a common disorder characterized by burning of the eye and blurry vision related to tear film abnormalities, increased tear evaporation, and ocular surface inflammation [3]. Based on early studies of MGD in rabbits, mice, primates and humans [4][5][6][7], a general mechanism associated with hyperkeratinization of the meibomian gland orifice causing ductal plugging, dilation, and a disuse acinar atrophy has been proposed as the most common cause of MGD [8]. ...
... It is likely that as meibum flow is decreased, internal ductal pressure may have effects on the lateral wall of the common duct causing increased mechanical strain. While 'acinar disuse atrophy' is an often-cited mechanism for obstructive MGD [8], a more plausible alternative is that reduced meibum flow regardless of cause leads to increased mechanical strain and stretching of the ductal and acinar cells that cause downstream effects on cell differentiation. To more clearly understand these potential effects, a more complex modeling of the entire meibomian gland is needed, which requires better understanding of the tissue compliance of the ductal epithelium and surrounding extracellular matrix. ...
This is the very first finite element modeling paper in Meibomian gland dysfunction, a common cause of dry eye. The results are of great interest as they support a novel pathophysiologic theory of Meibomian gland dysfunction, which also has an impact on therapeutic issues.
... MGD can be classified into three categories based on whether the terminal duct is obstructed and the quantitative and qualitative characteristics of glandular secretion are affected: hypersecretory, hyposecretory, and obstructive, with the latter generally considered the most common form [56]. The obliteration of meibomian gland ducts and obstruction of orifices due to hyperkeratinization are significant findings in hyposecretory MGD [57]. ...
The meibomian glands produce a lipid-rich secretion that forms the superficial layer of the tear film, preventing excessive evaporation. Dysfunction of these glands (MGD) is the primary cause of dry eye disease (DED), a growing public health concern. Currently, there are limited pharmacological treatments for DED. However, α-/β-melanocyte-stimulating hormones (α-/β-MSH), ligands of the melanocortin receptors (MCR), are known to regulate lipogenesis and differentiation in sebaceous glands. This study investigated the influence of α-/β-MSH on exocrine secretion in human meibomian glands. Methods: Immunohistochemistry and RT-PCR for MCR expression were performed in human meibomian glands and an immortalized human meibomian gland epithelial cell line (ihMGECs). The effects of α-/β-MSH (agonists) and JNJ-10229570 (antagonist) in ihMGECs on lipid production and MCR response were analyzed using Oil-RedO staining, transmission electron microscopy, qPCR, and a cAMP assay. Additionally, the effect of α-/β-MSH on an ex vivo organotypic slice culture (OSC) of human eyelids was investigated. Results: MCR expression was confirmed in human meibomian glands. Stimulation with α-/β-MSH increased cAMP levels and MCR expression. α-/β-MSH dose-dependently induced lipid production in ihMGECs and OSC, resulting in increased lipid droplet formation and upregulation of lipogenesis markers. Co-administration of JNJ-10229570 suppressed this effect. Conclusion: Our data show for the first time that human meibomian glands express MCRs and that stimulation/ inhibition of MCRs alters cAMP response, MCR expression, and lipogenesis markers, thereby affecting the genesis of meibum. Therefore, α-/β-MSH positively impacts meibum production and should be considered in the context of changes in glandular secretion in MGD and potential treatments.
... Meibomian gland dysfunction (MGD) is a chronic and diffuse ocular condition characterized by obstruction of the terminal duct of meibomian gland (MG) or abnormal tear secretion [1][2][3][4]. Recent clinical studies have indicated a common occurrence of abnormal serum cholesterol levels in patients with mild to severe eye dysfunction [5][6][7][8][9][10][11][12]. ...
Aim
To explore the regulatory mechanism of meibomian gland (MG) in hyperlipidemic mice under a diurnal rhythm by transcriptomic analysis based on high-throughput sequencing.
Methods
The mouse model of hyperlipidemia induced by four months of high-fat diet (HFD) feeding to a regular light–dark (LD) cycle for 2 weeks was used in this study. Phenotypic observation and RNA sequencing (RNA-seq) of MGs of the experimental mice were then performed to investigate transcriptional changes due to hyperlipidemia and the diurnal rhythm and their effects on meibomian gland dysfunction (MGD).
Results
The expression levels of the identified dysregulated genes were then validated by qRT–PCR. Several significantly regulated genes and enriched pathways were identified as associated with MGD in hyperlipidemic mice under a diurnal rhythm; these genes included some core diurnal clock genes, e.g., Clock, Per2 and Per3. Phenotypic and histological analysis reveals abnormal morphology concomitantly with a modification of the transcriptional landscape of MG caused by HFD.
Conclusion
Our findings provide us with a deeper understanding of the diurnal rhythm regulation of MG in hyperlipidemic mice altered by daily nutritional challenge.
... Meibomian glands secrete the lipid component of the tears, which contribute to increased lubrication, surface wettability, and tear breakup time (TBUT). 2,8,10,[16][17][18][19][20][21][22][23] This lipid layer also helps in tear distribution in an evenly manner, as well as preventing tear spillage from the palpebral margins and sealing the eyelids during sleep. 8,15 MGD is diagnosed based on a myriad of clinical features, such as conjunctival blood vessel ingurgitation, foamy tear film, Meibomian gland ostial dilation and increased viscosity of their secretions, and corneal epithelial damage secondary to TF instability. ...
Purpose
To compare the meibographies and dry eye parameters of paretic vs non-paretic sides of patients with a facial palsy diagnosis.
Patients and Methods
Twenty patients with unilateral facial palsy were recruited and the severity of the disease was staged using the House-Brackmann scale. A comprehensive dry eye evaluation was performed using the Oculus 5M Keratograph. A Pearson correlation coefficient was performed to determine correlation strength between House-Brackmann score and Meibomian gland atrophy. Meibographies were analyzed via ImageJ software to determine the affected area, and they were compared to the observer manual score. Cohen’s Kappa coefficient was calculated to compare agreement between manual and ImageJ meibography scoring.
Results
Tear breakup time was reduced in the affected side (p = 0.21), tear meniscus height was much greater in the non-affected side (p = 0.02). Finally, Meibomian gland alterations were more evident in the affected side, with upper Meibomian glands having a loss of 29.55 ± 13.31% (p = 0.03) and lower glands presenting a loss of 44.44 ± 16.9% (p =< 0.001). Pearson correlation coefficient between House-Brackmann score and Meibomian gland atrophy was 0.841 (p < 0.001 [95% CI: 0.64–0.94]). Cohen’s kappa coefficient was 0.643 (p < 0.001).
Conclusion
A clear difference in Meibomian gland and tear film dynamics can be observed in paretic vs non-paretic sides. A greater House-Brackmann score was correlated with a greater Meibomian gland atrophy area. A strong positive correlation is seen between the House-Brackmann score and Meibomian gland atrophy. Software-based analysis also showed a greater glandular area loss when compared to clinician’s analysis. The level of agreement was moderate, so disparities are observed, especially in grade 2 Meibomian gland dropout where the least level of agreement was seen in cross tabulation. This study further incentivizes multimodal patient evaluation, which has been a growing area of interest in healthcare.
... The correlation between blinking dynamics and meibomian gland dysfunction (MGD) plays a critical role in the pathogenesis of DED [33]. Meibomian glands secrete meibum, a lipid substance which serves as a barrier to reduce tear evaporation [34,35]. Normal blinking behavior ensures the consistent delivery and even distribution of meibum across the ocular surface [36,37]. ...
Dry eye disease (DED) has become increasingly prevalent in the digital era, largely due to prolonged screen exposure. The excessive use of digital devices contributes to inappropriate blink frequency and dynamics, leading to ocular surface dryness and discomfort. Additionally, digital screen use has broader implications for systemic health, including visual strain, headaches, and disrupted circadian rhythms caused by blue light exposure. Previous studies have shown that prolonged screen time correlates with altered blink frequency and increased symptom severity in DED patients, exacerbating the imbalance in tear film production and evaporation. Blinking dynamics, particularly blink rate and completeness, are crucial in maintaining ocular surface moisture. Incomplete blinking impairs meibomian gland function, reducing lipid secretion, which is essential for preventing tear evaporation. Raising patient awareness through educational material, ergonomic adjustments, and blinking exercises has been shown to mitigate these effects. Digital tools that provide targeted educational interventions can be particularly effective in improving blink dynamics and overall ocular comfort. This study evaluates the efficacy of digital applications in optimizing blinking dynamics and enhancing tear film stability. The findings suggest that these innovations improve patient outcomes by encouraging healthier eye care practices. However, further research is needed to assess their long-term impact across diverse populations.
... MGD is a prevalent condition that contributes to OSD via obstruction and alterations in the meibomian gland secretions. 19 While conservative management is the primary approach for MGD treatment, antibiotics with antiinflammatory properties are recommended for severe cases. 5 Oral doxycycline and oral azithromycin are commonly prescribed antibiotics for managing MGD. ...
Purpose
The first-line treatment approach of Meibomian gland dysfunction (MGD) comprises conservative management, but antibiotics with anti-inflammatory properties are recommended in severe or persistent cases. Oral doxycycline and oral azithromycin are commonly used antibiotics for managing MGD. However, a systematic review and meta-analysis comparing their efficacy and safety is needed.
Patients and Methods
This study adhered to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and included randomized controlled trials (RCTs) focusing on patients with MGD. The primary outcomes assessed were symptom score, sign score, and overall clinical response. Adverse events were also evaluated. Multiple databases were comprehensively searched, and data extraction and quality assessment were performed by two independent authors.
Results
Four trials and a quasi-experimental study involving 612 participants/eyes were included. Meta-analysis showed a statistically significantly lower mean sign score in the oral azithromycin group than in the doxycycline group. However, one RCT reported a lower mean symptom score in the doxycycline group. No significant differences were found in the means of total scores between the two groups. Systemic adverse events such as nausea, abdominal cramps, decrease in appetite, and diarrhea were more prevalent in the doxycycline group.
Conclusion
The systematic review and meta-analysis suggest that oral azithromycin may be more effective in reducing signs of MGD than oral doxycycline. However, the results regarding symptom scores and total scores were inconclusive. Azithromycin also demonstrated a better safety profile with fewer gastrointestinal adverse events. Further research is needed to determine the optimal antibiotic treatment for MGD.
... The tarsal plate is the most important component of the eyelid and is composed of dense connective tissue, abundant elastic fibers, and numerous meibomian glands [1,2]. In addition, the tarsal plate is present in both the upper and lower eyelids and not only serves as a structural support for maintaining the shape of the eyelid but also contributes to the stabilization of the tear film and prevents the cornea from drying out by forming the lipid layer of the tear layer, with lipid components secreted from the meibomian gland in the tarsal plate [3,4]. ...
Background: The aim of this study was to develop 3D-bioprinted scaffolds embedded with human adipose-derived stem cells (hADSCs) to reconstruct the tarsal plate in a rat model. Methods: Scaffolds were printed using a 3D bioprinter with a bioink composed of atelocollagen and alginate. hADSCs (5 × 10⁵ cells/mL) were embedded within the bioink. A total of 30 male Sprague Dawley (SD) rats (300 g) were divided into three groups: group 1 (normal control, n = 10), group 2 (3D-bioprinted scaffolds, n = 10), and group 3 (3D-bioprinted scaffolds with hADSCs, n = 10). Four weeks after surgery, a histopathological analysis was performed using hematoxylin and eosin (H&E) staining, Masson’s trichrome (MT) staining, and immunofluorescence staining. Gene expression of SREBP-1, PPAR-γ, FADS-2, and FAS was assessed via real-time polymerase chain reaction (PCR). Results: No abnormalities were observed in the operated eyelids of any of the 30 rats. The histopathological analysis revealed lipid-secreting cells resembling meibocytes in both group 2 and group 3, with more pronounced meibocyte-like cells in group 3. Immunofluorescence staining for phalloidin expression showed a significant increase in group 3. Additionally, the RNA expression of SREBP-1, PPAR-γ, FADS-2, and FAS, all related to lipid metabolism, was elevated in group 3. Conclusions: The 3D-printed scaffolds combined with hADSCs were effective for tarsal plate reconstruction, with the hADSCs notably contributing to the generation of cells associated with lipid metabolism.
... Sullivan et al. (2010) measured dry eye signs and symptoms in each eye of 299 subjects, approximately half of whom were dry eye patients and the other half normal volunteers. Measurements of dry eye indicator variables for each subject eye included tear osmolarity (in mOsm/L), tear volume (Schirmer's test expressed as mm of wetting of a filter paper wick making contact with the eye under the lower lid), tear film breakup time (TBUTin seconds post blink), meibomian gland dropout score (Foulkes & Bron, 2003), corneal staining-type score (NEI/Industry Workshop fluorescein staining-type scoring system), corneal staining area score, conjunctival staining-type score (NEI/Industry Workshop scoring system), conjunctival staining area score, and Ocular Surface Disease Index (OSDI) rating scale questionnaire raw score (patient self-report of symptom severity) (Schiffman et al., 2000). Indicator variable values have either a positive monotonic relationship with dry eye severity (e.g., tear osmolarity increases as dry eye worsens) or a negative monotonic relationship with dry eye severity (e.g., TBUT decreases as dry eye worsens). ...
... (MMP-9) in tears [121]. MMP-9 is recognized as an inflammation biomarker of chronic ocular surface inflammation (OSI), including DES and meibomian gland dysfunction [122,123]. To achieve a transparent and scalable biosensor structure, the graphene-based hybrid with randomly distributed AgNWs was combined with the original graphene channel for the source and electrodes, leveraging the superior electrical and mechanical properties of graphene-AgNW hybrids [71]. ...
The eye is a remarkably intricate organ, encompassing various healthrelated biophysical signals and biochemical signals. Smart contact lenses (SCLs) have
emerged as wearable intelligent devices capable of noninvasively and continuously
monitoring these signals in the eyes. Recent advancements in wearable SCLs
have significantly transformed the landscape of physiological signal monitoring for
health-related diseases. Herein, this review aims to comprehensively explore and
emphasize a selection of materials, specifically focusing on their integration into SCLs with different physiological signal outputs for health monitoring. We also provide rational design strategies to help researchers make decisions when developing SCLs with desired selection criteria depending on physiological signals, sensing materials, signal outputs, and applications. Finally, the challenges and perspectives for the next generation of SCLs are proposed.
... A specific threshold value of 5 was determined as the cutoff point for diagnosing MGD. [22] Those with an MGD score above 5 were excluded from both groups. ...
Purpose
To perform tear meniscus particle analysis using anterior segment spectral domain-optical coherence tomography (SD-OCT) and ImageJ software in keratoconus patients.
Methods
A total of 76 participants (76 eyes) were included in the study. A comprehensive analysis of tear meniscus parameters, including tear meniscus height (TMH), tear meniscus depth (TMD), tear meniscus turbidity (TMT), and percentage of area occupied by particles (PAOP) within the meniscus, was performed in kerataconus patients and healthy controls.
Results
TMT was significantly higher in the keratoconus group, while PAOP was significantly lower ( P < 0.05). However, TMH and TMD did not show significant differences between the two groups ( P > 0.05). There was a negative correlation observed between TMT and PAOP. In binary logistic regression analysis, TMT and Schirmer score were found to be the most influential factors in predicting keratoconus (odds ratio [OR] = 0.995, P = 0.039 and OR = 1.143, P = 0.021, respectively).
Conclusion
This study revealed novel findings on analysis of the tear film in keratoconus patients, with higher TMT and lower POAP levels in the keratoconus group compared to the healthy control group.
... The grading of severity of meibomian gland disease was assessed as described by Foulks and Bron. [12] The flare was graded as per the Uveitis Nomenclature Working Group grading system, and when present, the cataract was evaluated by the Lens Opacities Classification System III. [13,14] All patients were provided treatment as per standard protocols (systemic corticosteroids with or without disease-modifying agents) followed in the clinics. ...
Background
Ocular involvement in autoimmune bullous dermatoses (AIBD) remains underappreciated.
Objectives
The objective was to study the prevalence and characteristics of ocular involvement in patients with AIBD.
Methods
The medical records of 25 patients (males: females 11:14) aged between 27 and 85 years (mean ± standard deviation = 44.9 ± 15.6 years) with AIBD were analyzed retrospectively for clinico-epidemiological attributes and the presence of ocular abnormalities.
Results
There were 20 (80%) pemphigus patients, of which most were pemphigus vulgaris (PV, n = 14) and pemphigus foliaceus (PF, n = 6). Other 5 (20%) patients included bullous pemphigoid (BP, n = 4) and cicatricial pemphigoid (CP, n = 1). Seventeen (68%) patients comprising 11 (78.6%) of PV, 3 (50%) of PF, 2 (50%) of BP, and 1 (100%) of CP had 27 ocular abnormalities. Erosions of lid margins ( n = 3, 27.3%), blepharitis with meibomitis ( n = 1, 9.1%), chalazion ( n = 1, 9.1%), and conjunctival vesicles over bulbar conjunctivae ( n = 2, 18.2%), conjunctivitis (PV = 5, 45.5%, PF = 1, 33.3%), and symblepharon and keratoconjunctivitis sicca in one (9.1%) patient each, respectively, were major ocular manifestations in pemphigus. Entropion with trichiasis, shallow fornices, and corneal opacities were major abnormalities in patients with BP ( n = 2, 100%) and CP ( n = 1, 100%).
Conclusion
Ocular comorbidities vary in prevalence and severity between subtypes of AIBD. These are mainly from complications of ocular surface disease predominantly affecting the anterior segment of the eye. They are more severe in patients with CP compared to others. The study is limited by a single-center, retrospective-study design, a small number of patients in each group for stratification, and long-term follow-up.
... The quantification of MG loss by meibography has rapidly become popular for the diagnosis of MGD, but other features of the MGs also play an important role in the pathophysiology of the disease, such as eyelid margin abnormalities [12,[32][33][34]. The ortho-DA analysis performed in the present study was able to discriminate between group 1 and group 2 according to the presence of different lipids species and MG loss. ...
Meibomian Glands (MG) are sebaceous glands responsible for the production of meibum, the main component of the Tear Film Lipid Layer (TFLL). The TFLL facilitates the spread of the tear film over the ocular surface, provides stability and reduces tear evaporation. Alterations in meibum composition lead to different ocular alterations like Meibomian Gland Dysfunction (MGD) and subsequent Evaporative Dry Eye (EDE). The aim of the present study was to investigate the composition and abundance of meibum lipids and their relationship with eyelid margin abnormalities, lipid layer patterns and MG status. The study utilizes a lipidomic approach to identify and quantify lipids in meibum samples using an Elute UHPLC system. This system considered all four dimensions (mass/charge, retention time, ion mobility and intensity) to provide the accurate identification of lipid species. Samples were categorized as healthy or low/no signs of alteration (group 1) or severe signs of alteration or EDE/MGD (group 2). The current investigation found differences in Variable Importance in Projection lipid abundance between both groups for the MGD signs studied. Changes in meibum composition occur and are related to higher scores in eyelid margin hyperaemia, eyelid margin irregularity, MG orifice plugging, MG loss and lipid layer pattern.
... 1 2 MGD is often found in clinical practice and is a main cause of evaporative dry eye disease in the elderly. [3][4][5] Morphological changes called meibomian gland drop-out (MG drop-out) can be seen in vivo with a technique called meibography. 6 Meibography can help evaluate morphological changes, assess the degree of MG drop-out, guide treatment decisions and monitor therapeutic effects as well as patient education tools to improve adherence. ...
Objective
The objective of this study is to determine the validity and reliability of the red filter meibography by smartphone compared with infrared in assessing meibomian gland drop-out.
Methods and analysis
An analytical cross-sectional study was done with a total of 35 subjects (68 eyes) with suspected MGD based on symptoms and lid morphological abnormalities. Meibomian glands were photographed using two smartphones (Samsung S9 and iPhone XR) on a slit-lamp with added red filter. Images were assessed subjectively using meiboscore by the two raters and drop-out percentages were assessed by ImageJ.
Results
There was no agreement in meiboscore and a minimal level of agreement in drop-out percentages between red filter meibography and infrared. Inter-rater reliability showed no agreement between two raters. Intra-rater reliability demonstrated weak agreement in rater 1 and no agreement in rater 2.
Conclusion
Validity of the red filter meibography technique by smartphones is not yet satisfactory in evaluating drop-out. Further improvement on qualities of images must be done and research on subjective assessment was deemed necessary due to poor results of intrarater and inter-rater reliability.
... Infrared imaging has emerged as an effective clinical technique for assessing the morphological characteristics of the MGs [4] . Ophthalmologists employ these images to observe and analyze various MGs features, providing valuable insights for diagnosing MGD [5] . However, relying solely on visual observation and clinical experience is subjective and yields relatively low reproducibility. ...
AIM: To investigate a pioneering framework for the segmentation of meibomian glands (MGs), using limited annotations to reduce the workload on ophthalmologists and enhance the efficiency of clinical diagnosis. METHODS: Totally 203 infrared meibomian images from 138 patients with dry eye disease, accompanied by corresponding annotations, were gathered for the study. A rectified scribble-supervised gland segmentation (RSSGS) model, incorporating temporal ensemble prediction, uncertainty estimation, and a transformation equivariance constraint, was introduced to address constraints imposed by limited supervision information inherent in scribble annotations. The viability and efficacy of the proposed model were assessed based on accuracy, intersection over union (IoU), and dice coefficient. RESULTS: Using manual labels as the gold standard, RSSGS demonstrated outcomes with an accuracy of 93.54%, a dice coefficient of 78.02%, and an IoU of 64.18%. Notably, these performance metrics exceed the current weakly supervised state-of-the-art methods by 0.76%, 2.06%, and 2.69%, respectively. Furthermore, despite achieving a substantial 80% reduction in annotation costs, it only lags behind fully annotated methods by 0.72%, 1.51%, and 2.04%. CONCLUSION: An innovative automatic segmentation model is developed for MGs in infrared eyelid images, using scribble annotation for training. This model maintains an exceptionally high level of segmentation accuracy while substantially reducing training costs. It holds substantial utility for calculating clinical parameters, thereby greatly enhancing the diagnostic efficiency of ophthalmologists in evaluating meibomian gland dysfunction.
... Posterior blepharitis, on the other hand, is caused by dysfunction of the meibomian glands, which secrete lipids that form the outer layer of the tear film. Dysfunction of the meibomian glands can lead to alterations in the lipid composition of the tear film, resulting in evaporative dry eye and inflammation of the eyelid margins [8,9]. ...
Blepharitis is a common chronic inflammatory condition affecting the eyelid margins; the pathophysiology of blepharitis is complex and not fully understood. The disease is anatomically divided into anterior (inflammation of eyelashes) and posterior (meibomian gland dysfunction) types. Diagnosis relies on clinical examination, revealing characteristic features like scurf, vascular changes, and meibomian gland dysfunction. The main goals of blepharitis treatment are symptom relief, recurrence prevention, and complication risk minimization. Treatment options include lid hygiene, topical and systemic antibiotics, topical corticosteroids, and omega-3 supplements. However, it is important to highlight reported cases of blepharitis as side effects of systemic therapies, particularly in the context of chemotherapy, bortezomib, cetuximab, TNFα inhibitors, and dupilumab. It is crucial to monitor patients undergoing such treatments regularly and attentively in order to promptly set up adequate supportive therapy. Of even more importance is future research on the pathophysiological mechanisms responsible for the occurrence of these ocular side effects in order to find a nosological cure for the issue.
... The TMH in Group A decreased significantly at postoperative 1 week compared to that at baseline because the lipid layer was thinner then, and the evaporation of the tear film increased correspondingly 24 . The outermost layer of the tear film, the tear film lipid layer, plays an important role in maintaining tear film stability and preventing tear evaporation [25][26][27][28] . Tear film lipid layer deterioration leads to tear film instability and evaporative dry eye 29 . ...
To evaluate the changes of dry eye parameters after small incision lenticule extraction (SMILE) surgery in patients with different ocular surface disease index (OSDI) scores. Prospective research. Participants were divided into two groups: Group A, OSDI < 13; and Group B, OSDI ≥ 13. The OSDI scores, tear meniscus height (TMH), first non-invasive tear film break-up time (NIBUT-First), and meibomian gland loss (MGL, %) were recorded at postoperative 1 -week and 1-month.113 eyes (57 patients) were enrolled, 70 eyes in Group A, and 43 eyes in Group B. In Group A, the OSDI scores significantly increased at 1-week and 1-month postoperative (all P < 0.001); the TMH, NIBUT-First and lipid layer grade significantly decreased at postoperative 1-week (P = 0.003, 0.005, 0.007, 0.004, respectively), but returned to preoperative level at 1-month postoperative. In Group B, only the lipid layer grade significantly decreased at postoperative 1-week (P < 0.05). Patients with different preoperative OSDI scores may experience different changes early after SMILE surgery. Patients with OSDI scores < 13 may experience more dramatic changes in dry eye symptoms which would resolve, while subjective complains could still exists at 1 month after surgery.
... This results in a range of symptoms, including dry eye, eye discomfort, and tear film instability [1]. The causes of MGD are numerous, including terminal gland obstruction caused by hyperkeratinization of the orifice [2], and changes in glandular secretion, leading to a detrimental effect on the homeostasis and integrity of the ocular surface [3,4]. ...
... This exposure to chemicals generated by exploration can result in ocular disorders, which reduces manpower, lowering the total output and production in the community [24,25]. Therefore, adequate ocular pharmaceutical cares, as well as government intervention are very necessary in this region because uncontrolled exposure could lead to partial or total blindness. ...
Background: The eye provides vision, can receive and process visual detail, and enables several photo response functions. Crude oil is a mix of different chemicals; it may be irritating or cause mild to severe conditions when in contact with the eyes . Aim: the study aimed to analyze the prevalence and therapeutic interventions of ocular disorders among the two communities in Southern, Ijaw, Bayelsa, Nigeria. Method: A descriptive cross-sectional design was used to describe the ocular disorders in selected crude oil-producing communities in the Niger Delta. A sample of 400 individuals from Korokorosei (200) and Amassoma (200) communities were enlisted using the convenience sampling technique; the questionnaire was administered and retrieved after filling. Results: There was a high prevalence of ocular disorders in Korokorosei than in Amassoma, and also a majority of the respondents visited the
local medicine outlet to get medication in the management of ocular disorders. Respondents from Korokorosei visit the local clinic for treatment; when they had ocular disorder (11% - always, 66% -
sometimes, 23%, etc.), 22% (always). 29.5% - always, 65% - sometimes,
5.5% - rarely visit the pharmacy for necessary checks and get medication
to treat eye disorders, 6.5%-always, 42%-sometimes, 34%-never visit
traditional healer for herbal treatment, 18.5%-always, 52%-sometimes,
29.5%-rarely visit an eye doctor for treatment, 30.5%-always, 64%-
sometimes, 5.5%-rarely indicated they make effort to handle the treatment by themselves and 24%-always, 82.5%-sometimes, 5.5%- rarely also said they buy medicines from drug sellers in vehicles and open market to handle their eye problem. Conclusion: The prevalence of ocular diseases and related problem were seen more in the oil-producing community than in the non-oil-producing community, and pharmaceutical intervention in these communities was very minimal.
... Meibomian glands secrete the lipid component of the tears, which contribute to increased lubrication, surface wettability, and tear breakup time (TBUT). 2,8,10,[16][17][18][19][20][21][22][23] This lipid layer also helps in tear distribution in an evenly manner, as well as preventing tear spillage from the palpebral margins and sealing the eyelids during sleep. 8,15 MGD is diagnosed based on a myriad of clinical features, such as conjunctival blood vessel ingurgitation, foamy tear film, Meibomian gland ostial dilation and increased viscosity of secretions, and corneal epithelial damage can be appreciated by slitlamp examination. ...
Purpose: To describe the correlation between facial palsy of any etiology and Meibomian gland dysfunction and to report the tear film parameters found in patients with facial palsy diagnosis. Design: Observational, longitudinal, and comparative study. Methods: A sample of 20 patients with unilateral facial palsy was obtained its severity was staged using the House-Brackmann scale. A dry eye evaluation using an Oculus 5M keratograph was performed, which included infrared meibography, tear breakup time, and a dry eye questionnaire. Meibographies were analyzed using ImageJ software to determine the affected area. Results: 11 patients (55%) were
female, mean age of diagnosis was 57.80 plus-or-minus sign 18.28 (range of 22-80), 10 (50%) cases were due to Bell's palsy. Tear breakup time was markedly reduced in the affected side but was statistically insignificant (p=0.2167) and tear meniscus height was much greater in the non-affected side (p=0.0199). Finally, Meibomian gland alterations were more evident in the affected side, with upper Meibomian glands having a loss of 29.55 plus-or-minus sign 13.31 percent (p=0.0374) and lower glands presenting a loss 44.44 plus-or-minus sign 16.9 percent (p=<0.001). Conclusions: A clear difference in Meibomian gland and tear film dynamics can be observed in paretic vs non paretic sides in the same patients. Multiple mechanisms contribute to this ailment, such as an incomplete blinking pattern and Meibomian gland dysfunction due to orbicularis oculi weakness. Software based analysis also showed a greater glandular area loss when compared to clinician's analysis, which may help aide in therapeutic decisions for patients with meibomian gland dysfunction.
... MG atrophy and dropout are the pathognomonic features of MGD, and conventionally thought to be caused by obstruction of the meibomian gland secretory duct leading to cystic dilation of ducts and acini causing a disuse acinar atrophy and a hyposecretory disease [50]. Other histopathologic features that have also been identified in human MGD including; basement membrane thickening, granulation, keratinization of the MG ducts and orifices and lipogranulomatous inflammation [51]. ...
Meibomian glands (MGs) secrete lipid (meibum) onto the ocular surface to form the outermost layer of the tear film. Proper meibum secretion is essential for stabilizing the tear film, reducing aqueous tear evaporation, and maintaining the homeostasis of the ocular surface. Atrophy of MG as occurs with aging, leads to reduction of meibum secretion, loss of ocular surface homeostasis and evaporative dry eye disease (EDED). Since MGs are holocrine glands, secretion of meibum requires continuous self-renewal of lipid-secreting acinar meibocytes by stem/progenitor cells, whose proliferative potential is dramatically reduced with age leading to MG atrophy and an age-related meibomian gland dysfunction (ARMGD). Understanding the cellular and molecular mechanisms regulating meibocyte stem/progenitor cell maintenance and renewal may provide novel approaches to regenerating MG and treating EDED. Towards that end, recent label retaining cell and lineage-tracing experiments as well as knock-out transgenic mouse studies have begun to identify the location and identities of meibocyte progenitor cells and potential growth and transcription factors that may regulate meibocyte renewal. In addition, recent reports have shown that ARMGD may be reversed by novel therapeutics in mice. Herein, we discuss our current understanding of meibocyte stem/progenitor cells and the hunt for gland renewal.
... The glands of affected individuals often show terminal duct obstruction, inflammation, and changes in glandular secretion. The condition is diagnosed based on various factors, including glandular dropout, reduced secretion upon gland expression, meibum secretion quality, inflammation, and meibography [1,2]. Treatments for MGD in the setting of evaporative dry eye include warm compresses, lid hygiene, intraductal meibomian gland probing, lipid-emulsion eye drops, thermal pulsation, n-acetyl-cysteine, azithromycin, omega-3 fatty acid supplementation, cyclosporine A eye drops, and intense pulse-light therapy [3,4]. ...
Meibomian gland dysfunction (MGD) is associated with evaporative dry eye syndrome, which is characterized by a reduction in meibum secretion and tear film instability. Present treatments provide only temporary relief, thereby necessitating the exploration of novel therapeutic strategies for chronic treatment. This study aims to evaluate topical spironolactone, a medication with anti-mineralocorticoid, anti-androgenic, and anti-inflammatory properties, in treating dry eye. A retrospective observational study was performed on the medical records of 102 patients diagnosed with dry eye disease. These patients were categorized into two groups based on their Schirmer's tear test scores. Various clinical indicators, including subjective global assessment scores, visual acuity, keratitis, conjunctival staining scores, and lid margin health, were evaluated prior to and following treatment with topical spironolactone eye drops. The group with higher Schirmer's scores exhibited improvement in self-reported global assessment scores after treatment. Significant improvements were also observed in keratitis and conjunctival staining scores, visual acuity, and lid margin inflammation. Similarly, the group with lower Schirmer's scores demonstrated improvements in self-reported global assessment scores and visual acuity after treatment. Topical spironolactone may improve tear film quality and address the inflammatory processes associated with MGD and evaporative dry eye. Moreover, the topical administration of spironolactone in an ocular vehicle appears to be well tolerated and may mitigate the risk of systemic adverse effects. Further studies are warranted to explore the long-term effects of topical spironolactone in the treatment of evaporative dry eye disease.
... Obstructive meibomian gland dysfunction (MGD) is the most common cause of evaporative dry eye disease, characterized by stagnation of meibomian gland lipids with or without qualitative / quantitative changes in meibum. Hyposecretion of lipids may result in tear lm instability, ocular irritation, and ultimately [7][8][9] ocular surface disease. ...
Introduction- Modern cataract surgery despite having favourable outcome in most of the aspects, comes with an unavoidable complication i.e. dry eye. Dry eye syndrome is an ocular surface disease either due to lacrimal undersecretion or overevaporation. Obstructive meibomian gland dysfunction (MGD) is the most common cause of evaporative dry eye disease, characterized by stagnation of meibomian gland lipids with or without qualitative/quantitative changes in meibum. Hyposecretion of lipids may result in tear lm instability, ocular irritation, and ultimately ocular surface disease. To study the prevalence of meibomian gland dysfunction in pa Aim: tients undergoing cataract surgery in A Tertiary Care Center in Barabanki. The present study was Cross sectional and was conducted from Materials and method: September 2021 to November 2022. It included 130 patients presented to ophthalmology department with the chief complaint of diminution of vision and was evaluated thoroughly under slit lamp for cataract and MGD and underwent a series of tests like Schirmer's Test, TFBUT, Ocular Protection index, MGD grading and DEQS. After examining 130 patients with varying cataract status, MGD (Dry Result: eye) was found to have a prevalence of 49.2% (59 out of 120). The mean age of the study participants was 57.54 (7.67) years. Among the patients, 30 (25.0%) were of aged 40-50 years, 45 (37.5%) were aged 51- 60 years, 43 (35.8%) were aged 61-70 years and rest 2 (1.7%) were of aged more than 70 years. Among the study participants, 65 (54.2%) were males and 55 (45.8%) were females. Addressing MGD and DED before cataract sur Conclusion: gery is important to achieving the best visual outcomes.To achieve optimum patient compliance and quality of life post-operatively, screening for dry eye should be made part of the protocol for pre-operative evaluations
Meibomian gland dysfunction (MGD) is a leading cause of dry eye disease, characterized by abnormal meibum production and glandular obstruction, resulting in compromised tear film stability and ocular discomfort. This review article aims to provide a comprehensive overview of the latest developments in the diagnosis and treatment of MGD. Diagnostic innovations, including non-invasive imaging techniques, tear film analysis, and interferometry, have enhanced our ability to detect early-stage MGD and assess disease severity more accurately. Newer therapeutic modalities like intense pulsed light therapy, and pharmacological agents targeting inflammation and glandular function, along with standard measures like hot fomentation, eyelid massage have shown promising results in improving symptoms and restoring meibomian gland health. By summarizing the current landscape of MGD diagnostics and therapeutics, this article highlights the ongoing efforts to refine clinical care and enhance patient outcomes in this prevalent ocular condition.
Background/Aims: To investigate the effectiveness of re-esterified triglyceride form of omega 3 (rTG-omega 3) on patients with meibomian gland dysfunction (MGD) after cataract surgery. Methods: This multicenter, randomized, investigator-blinded, clinical study was conducted between June 2021 and March 2023 and enrolled 107 patients with MGD who had undergone cataract surgery within 3 months at seven sites across South Korea. Patients were randomly assigned to rTG-omega 3 group or a control group. We compared (1) tear film break-up time (TBUT) (s), (2) corneal fluorescein staining score [National Eye Institute/Industry (NEI) scale], (3) conjunctival fluorescein staining score (NEI scale), (4) strip meniscometry (SM) tube score (mm), (5) MGD stage, (6) MG quality, (7) MG expressibility, (8) Standard Patient Evaluation of Eye Dryness (SPEED) score, and (9) Ocular Surface Disease Index (OSDI) scores at baseline and 6 and 12 weeks. Results: TBUT, corneal fluorescein staining score, and SM tube score were significantly improved in the rTG-omega 3 group compared with control group (P = 0.005, P = 0.003, and P = 0.0049, respectively). Subjective questionnaire responses were also improved significantly (SPEED score, P = 0.022; OSDI score, P = 0.0011). MGD parameters were not significantly different. However, during subanalysis, significant improvements in MG quality and expressibility were observed in the MGD stage 4 group with rTG-omega 3 supplementation (P = 0.0177 and P = 0.0205, respectively). Discussion: rTG-omega 3 supplementation facilitated improvements in both objective and subjective parameters. In particular, MG quality and expressibility were significantly improved in the severe MGD group.
Purpose: Meibomian gland dysfunction (MGD) may cause chronic ocular surface pain (COSP) with a neuropathic component that can significantly impact quality of life and be poorly responsive to conventional treatments of MGD. Intense pulsed light (IPL) is an emerging treatment already acknowledged as improving refractory MGD, potentially modulating inflammatory mediators on the ocular surface. This study aimed to assess the impact of IPL on COSP associated with unresponsive MGD. Methods: A monocentric prospective study has been conducted from 2021 to 2023 on patients presenting with moderate MGD and COSP non-responsive to conventional treatments of MGD. Neuropathic pain components were suspected when severe discomfort (OSDI score above 33/100) was observed despite moderate objective signs. Three sessions of IPL were performed at a two-week interval. The primary outcome was change in OSDI at day 60. Secondary outcomes included OSDI modification at D120, DEQ-5, and Pentascore results at D60/D120, together with changes in clinical [Schirmer I, Fluorescein Break-up time (BUT), fluorescein staining, and MGD classification] and paraclinical tests [noninvasive BUT, tear meniscus height (TMH), and meibography]. Results: A significant improvement of COSP (p < 0.05 for changes in OSDI and Pentascore results) was observed 2 and 4 months after the last IPL session, together with an improvement in tear film stability, corneal epitheliopathy, meibomian gland obstruction, and TMH. Conclusion: The results of this study suggest the beneficial effect of IPL on neuropathic component of COSP associated with MGD. The underlying mechanisms involved in that improvement, presumably related to downgrading of inflammatory effectors, remain however to be explored.
Purpose
To evaluate the ability of swept-source optical coherence tomography angiography (SS-OCTA) to assess lid margin vascularity.
Methods
This prospective, cross-sectional trial enrolled 125 participants, including 15 control subjects and 110 meibomian gland dysfunction (MGD) patients. Lid margin blood flow density (LMBFD) was obtained using SS-OCTA. LMBFD was assessed for repeatability in 54 of 125 participants and for reproducibility in 23 of 125 participants. The efficacy of LMBFD was validated in the 125 participants, who were divided into mild (n = 46), moderate (n = 42), and severe groups (n = 37) according to the lid margin vascularity severity shown in the slit-lamp photographs. Correlations between LMBFD and MG-related parameters, such as ocular surface disease index (OSDI), fluorescein tear break-up time (FTBUT), cornea fluorescein staining (CFS), lid margin score (LMS), and meibomian gland expressibility (ME), were analyzed in all 125 participants.
Results
Repeatability and reproducibility coefficients were satisfactorily high in the scan mode with a scan area of 6 mm × 6 mm (intraclass correlation coefficient [ICC] repeatability = 0.905; ICC reproducibility = 0.986) and a scan area of 9 mm × 9 mm (ICC repeatability = 0.888; ICC reproducibility = 0.988). The LMBFD gradually increased in the mild, moderate, and severe groups (P < 0.001). LMBFD was significant correlated with OSDI (r = 0.290, P = 0.001), FTBUT (r = −0.195, P = 0.030), CFS (r = 0.352, P < 0.001), ME (r = 0.191, P = 0.033), and LMS (r = 0.370, P < 0.001).
Conclusions
LMBFD may be a noninvasive, repeatable, reproducible, and efficient index for the quantitative evaluation of eyelid margin vascularity in the future.
Translational Relevance
We demonstrated that SS-OCTA has the potential to evaluate the eyelid margin vascularity in MGD patients and guide future treatment strategies in clinics.
Importance
Taking ω-3 supplements has been associated with a reduction in symptoms of dry eye disease (DED) associated with meibomian gland dysfunction (MGD). However, a recent relatively large clinical trial concluded that treating DED with ω-3 consumption was ineffective, potentially warranting additional investigations.
Objectives
To investigate the effect of re-esterified triglyceride (rTG) ω-3 fatty acid supplementation on DED associated with MGD.
Design, Setting, and Participants
This double-masked, parallel-group, randomized clinical trial was conducted at 7 institutions from September 2020 to January 2023. Patients with DED associated with MGD were included and randomly assigned to the ω-3 group (received 1680 mg of eicosapentaenoic acid and 560 mg of docosahexaenoic acid), whereas those in the grape-seed group received 3000 mg of grape-seed oil daily.
Interventions
rTG ω-3 Fatty acid supplementation vs grape-seed oil.
Main Outcome Measures
The primary end point was the Ocular Surface Disease Index (OSDI) from baseline to 6 and 12 weeks. The safety parameters were visual acuity and intraocular pressure change.
Results
A total of 132 patients (mean [SD] age, 50.6 [13.8] years; 103 female [78.0%]) were included in this study. The mean (SD) baseline OSDI scores of the ω-3 and grape-seed groups were 43.5 (16.5) and 44.1 (16.6), respectively. A total of 58 patients (87.9%) and 57 patients (86.4%) in the ω-3 and grape-seed groups, respectively, completed 12 weeks of follow-up. There were no differences in compliance with the dietary supplement intake between groups (ω-3, 95.8% and grape-seed, 95.4%). The OSDI (SD) change from baseline to 6 and 12 weeks was −20.5 (16.0) and −22.7 (15.7), respectively, in the ω-3 group and −15.1 (20.2) and −18.8 (21.7), respectively, in the grape-seed control group (difference at 6 weeks = −5.4; 95% CI, −12.15 to 1.33; P = .12 and at 12 weeks = −3.9; 95% CI, −10.90 to 3.13; P = .28). There were no changes in safety parameters or adverse events related to taking the dietary supplement in either group.
Conclusions and Relevance
This randomized clinical trial did not show a benefit of the rTG form of ω-3 for ameliorating symptoms of DED associated with MGD, although fewer than 60 participants were evaluated in each group. Any secondary outcomes from this study should be considered for hypothesis generation of future evaluations of the effect of the rTG form of ω-3 on DED associated with MGD.
Trial Registration
CRIS Identifier: KCT0004927
Aim:
To assess the relationship between systemic inflammation markers and ocular surface parameters in hazelnut harvesters.
Material and method:
This prospective study included 30 patients presenting with moderate ocular surface diseases during the hazelnut harvesting season. A detailed ophthalmological examination was performed during the harvesting season and the first month after the end of treatment (control). Schirmer test, tear break-up time (TBUT), and ocular surface disease index (OSDI) scores were determined. In complete blood count analysis, in addition to the evaluation of inflammatory cells, the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and systemic immune-inflammation index (SII) were calculated.
Results:
Eosinophil percentage had a high level of negative correlation with the TBUT and Schirmer values and a high level of positive correlation with the OSDI score during the hazelnut picking season (r = -0.727, r = -0.735, r = 0.750, respectively). During the hazelnut harvesting season, the NLR and SII parameters had a moderate level of negative correlation with the TBUT (r = -0.29 and r = -0.276) and Schirmer (r = -0.33 and r = -0.298) values and a moderate level of positive correlation with the OSDI score (r = 0.389 and r = 0.264).
Conclusion:
In hazelnut harvesters, ocular allergy and inflammation may be associated with systemic biomarkers.
Background:
Meibomian gland dysfunction (MGD) is the most common underlying cause of dry eye disease (DED). MGD leads to pathological alteration of the composition or quantity of meibum, or both, which subsequently results in tear evaporation and the typical signs and symptoms associated with DED. The LipiFlow Thermal Pulsation System (LipiFlow) is a medical device used to treat MGD in office; however, it is unclear if LipiFlow can outperform other DED treatments.
Objectives:
To evaluate the effectiveness of LipiFlow for treating DED signs and symptoms and the safety of LipiFlow compared with sham or other available treatments for MGD in adults.
Search methods:
The Cochrane Eyes and Vision Information Specialist searched the electronic databases for randomized controlled trials. There were no restrictions on language or date of publication. We searched the Cochrane Central Register of Controlled Trials (CENTRAL, including the Cochrane Eyes and Vision Trials Register; 2022, Issue 6), MEDLINE Ovid, Embase.com, PubMed, LILACS (Latin American and Caribbean Health Science Information database), ClinicalTrials.gov, and World Health Organization International Clinical Trials Registry Platform (WHO ICTRP) electronic databases. We also examined the reference lists of identified trials, review articles, and guidelines for information about relevant trials that may not have been identified by our search strategy. We contacted investigators regarding ongoing trials. The last database search was performed on 24 October 2022.
Selection criteria:
We included studies conducted in adults (over 18 years of age) with DED or MGD as defined by the primary trial investigators. We imposed no restrictions on race, ethnicity, or sex. We considered trials involving contact lens wearers if they were equally represented between groups.
Data collection and analysis:
We applied standard Cochrane methodology.
Main results:
We included 13 trials that randomized a total of 1155 participants (28 to 236 participants randomized per study). Six trials were conducted in the USA, three in China, two in Thailand, one in France, and one in Italy. Eight trials were of single-center design, while four trials were of multicenter design; one trial did not report the number of participating centers. Study characteristics The study population of the included trials was 66% female (range 48% to 80%), with an age range of 19 to 86 years. LipiFlow, used as a stand-alone intervention, was compared with basic warm compresses in five studies, thermostatic device in five studies, oral intervention in one trial, and topical dry eye medications in one trial. LipiFlow was also evaluated together with eyelid hygiene product versus eyelid hygiene products alone in one trial. Findings Five trials compared LipiFlow with a basic warm compress applied for varying durations and frequencies during the trial period; only one of these trials combined a warm compress with eyelid massage. Analyzing symptom scores by different questionnaires (Ocular Surface Disease Index [OSDI] and Standard Patient Evaluation of Eye Dryness [SPEED]) yielded conflicting evidence of a difference in symptoms between LipiFlow and basic warm compresses after four weeks. There was no evidence of a difference in meibomian gland expression, meibum quality, or tear breakup time when comparing LipiFlow with basic warm compresses. Another five trials compared LipiFlow with thermostatic devices. Analysis of symptom scores at four weeks showed that thermostatic devices had reduced OSDI scores by a mean difference (MD) of 4.59 (95% confidence interval [CI] 1.23 to 7.95; I2 = 0, P = 0.007; 553 participants; very low certainty evidence) as compared with LipiFlow. When we compared LipiFlow plus eyelid hygiene with eyelid hygiene alone, there was no evidence of difference in signs or symptoms at any time point evaluated. Only one trial compared LipiFlow with a topical DED medication (lifitegrast 5%). The single-trial estimate suggested that 5% lifitegrast may increase meibomian gland expression scores compared with LipiFlow at day 42 (MD -1.21, 95% CI -2.37 to -0.05; 50 participants; low certainty evidence) by using a meibomian gland expression scale of 0 to 8. One trial compared LipiFlow with an oral intervention (doxycycline), finding that LipiFlow may result in significantly better SPEED scores than doxycycline at three months (MD -4.00, 95% CI -7.33 to -0.67; 24 participants; very low certainty evidence). No other significant differences in signs or symptoms were found between LipiFlow and doxycycline at three months. We did not find any other statistically significant differences in symptoms or signs for any other analysis performed in this review at the one- to four-week time point. Adverse events No trial reported any intervention-related, vision-threatening adverse events.
Authors' conclusions:
LipiFlow performs similarly to other commonly used DED treatments with regard to DED signs and symptoms. The best available evidence was deemed to have a high level of bias, leading to low or very low certainty evidence. Additional research with adequate masking, a standardized testing methodology, and a sample representative of the MGD population is therefore needed before any firm conclusions can be drawn regarding comparative benefits and harms.
Sixty-seven patients (38 woman; median age, 69 years) were enrolled to assess complement activation products (CAPs) in tear fluid with/without dry eye (DE) and with/without meibomian gland dysfunction (MGD). Patients were divided into four groups based on the presence/absence of DE and MGD: group DM had both DE and MGD, group DN had DE without MGD, group NM had MGD without DE, and group NN had neither DE nor MGD. The levels of C3a and C5a in the collected tears were analyzed using a cytometric bead array. The C3a concentrations in the DM, DN, NM, and NN groups were 2326 pg/ml, 1411 pg/ml, 1821 pg/ml, and 978 pg/ml, respectively. The C5a concentrations in the DM, DN, NM, and NN groups were 24.7 pg/ml, 15.3 pg/ml, 24.1 pg/ml, and 12.9 pg/ml, respectively. The concentrations of C3a and C5a in the DM and NM groups were significantly higher than in the NN group (P < 0.05 for both comparisons). The CAPs in the tear fluid in MGD and DE increased. Local dysregulation of the innate immune system can be associated with the development of MGD and DE in elderly patients.
In this study, we investigated whether a combination of 2-methacryloyloxyethyl phosphorylcholine (MPC) polymer with commercially available diquafosol sodium (DIQ eye-drops) or sodium hyaluronate eye drops (HYA eye-drops) enhances the therapeutic effect for dry eyes. An N-acetylcysteine-treated rabbit model was used to evaluate the therapeutic effect for dry eyes in this study. The instillation of eye-drops containing DIQ and HYA enhanced mucin levels, and promoted the improvement in the tear film breakup in the N-acetylcysteine-treated rabbit model. In addition, the combination of MPC polymer increased the dry eye therapy in DIQ eye-drops and HYA eye-drops. Although the mucin levels in the N-acetylcysteine-treated rabbit model were also enhanced by the combination of DIQ eye-drops and MPC polymer, the mucin levels were similar between HYA eye-drops co-instillated with or without MPC polymer. These results show that the combination of MPC polymer may enhance the therapeutic effect for dry eyes in commercially available eye-drops.
The eye contains a complex network of physiological information and biomarkers for monitoring disease and managing health, and ocular devices can be used to effectively perform point-of-care diagnosis and disease management. This comprehensive review describes the target biomarkers and various diseases, including ophthalmic diseases, metabolic diseases, and neurological diseases, based on the physiological and anatomical background of the eye. This review also includes the recent technologies utilized in eye-wearable medical devices and the latest trends in wearable ophthalmic devices, specifically smart contact lenses for the purpose of disease management. After introducing other ocular devices such as the retinal prosthesis, we further discuss the current challenges and potential possibilities of smart contact lenses.
Degenerative diseases of the outer retina, including age-related macular degeneration (AMD), are characterized by atrophy of photoreceptors and retinal pigment epithelium (RPE). In these blinding diseases, macrophages are known to accumulate ectopically at sites of atrophy, but their ontogeny and functional specialization within this atrophic niche remain poorly understood, especially in the human context. Here, we uncovered a transcriptionally unique profile of microglia, marked by galectin-3 upregulation, at atrophic sites in mouse models of retinal degeneration and in human AMD. Using disease models, we found that conditional deletion of galectin-3 in microglia led to defects in phagocytosis and consequent augmented photoreceptor death, RPE damage and vision loss, suggestive of a protective role.
Mechanistically, Trem2 signaling orchestrated the migration of microglial cells to sites of atrophy, and there, induced galectin-3 expression. Moreover, pharmacologic Trem2 agonization led to heightened protection, but only in a galectin-3-dependent manner, further signifying the functional interdependence of these two molecules. Likewise in elderly human subjects, we identified a highly conserved population of microglia at the transcriptomic, protein and spatial levels, and this population was enriched in the macular region of postmortem AMD subjects. Collectively, our findings reveal an atrophy-associated specialization of microglia that restricts the progression of retinal degeneration in mice and further suggest that these protective microglia are conserved in AMD.
One Sentence Summary
A common neuroprotective response of microglia at the site of retinal atrophy is identified in mice and humans.
Purpose:
To determine pathological changes of meibomian glands (MGs) after transient exposure of the rat eyelid margin to alkali solution.
Methods:
Filter paper infiltrated with 1 N sodium hydroxide solution was applied to the eyelid margin of Sprague-Dawley rats for 30 s under general anesthesia, without touching the conjunctiva, after which the ocular surface and eyelid margin were examined by slit-lamp microscopy. In vivo confocal microscopy and stereomicroscopy were subsequently applied to observe MG morphology on day 5, day 10 and day 30 post alkali injury. Eyelid cross-sections were processed for H&E staining, Oil red O staining and immunofluorescent staining.
Results:
After alkali injury, there was marked plugging of MG orifices, telangiectasia and hypertrophy of the eyelid margin, while corneal epithelium was intact at post-injury days 5 and 10. However, 30 days after alkali injury, mild corneal epithelial damage was observed. Degeneration of MG acini was observed at days 5 and became aggravated at days 10 and 30, along with MG duct dilation and acini loss. Oil red O staining showed lipid accumulation in the dilated duct. Inflammatory cell infiltration and the presence of apoptotic cells was seen in the MG loci 5 days post injury, but diminished at days 10 and 30. Cytokeratin 10 expression was increased in dilated duct, while cytokeratin 14, PPAR-γ, Ki67 and LRIG1 expression were decreased in the acini of injured loci.
Conclusions:
Transitory alkali exposure of the rat eyelid margin obstructs the MG orifice and induces pathological changes of MG dysfunction.
Purpose: The study is to evaluate the effect of demodex mite infection on the ocular surface characteristics changes of patients with dry eye disease (DED) using non-invasive instruments.
Methods: 127 patients with DED and 52 normal control subjects were enrolled in this study. All DED patients were divided into demodex negative group and demodex positive group based on the result of the demodex mite infection under microscope. Non-invasive tear break-up time (NIBUT), tear meniscus height (TMH), ocular redness, meibomian gland secretions (MGS), morphology of palpebral margin, meibomian gland loss score (MGLS), and cornea fluorescence staining (CFS) were evaluated under oculus corneal topography and slit-lamp.
Results: The demodex positive group showed longer NIBUT (P=0.003), lower TMH(P=0.021), worse morphology of palpebral margin (P＜0.001) and worse MGS (P=0.007) than demodex negative group. The score of ocular redness in patients with DED were higher than in the control group (P＜0.05). In demodex positive group, age had a positive correlation with the degree of palpebral margin morphological damage (rs=0.332 P＜0.05) and a negative correlation with the severity of meibomian gland loss (rs=-0.345 P＜0.05).
Conclusion: A significant association between demodex mite infection and abnormal morphology of the palpebral margin, a lower meibomian gland quality, and lacrimal gland hyposecretion in patients with DED. Prompt recognition of the possible co-occurrence of demodex mite infection in patients with DED is crucial for optimal management and improved patient comfort and prognosis.
To identify diagnostic accord and disagreement between general practitioners and an ophthalmologist and thereby determine how undergraduate and non-specialist postgraduate ophthalmic training could be improved.
Comparison of diagnosis of presenting conditions by general practitioners and one ophthalmologist in patients consulting general practitioners for ophthalmic problems during March 1989 to February 1990.
12 general practices in west Nottingham.
1474 patients presenting to the study general practitioners with new ophthalmic conditions or new episodes of recurrent conditions.
Diagnoses of general practitioners and ophthalmologist.
1121 (76%) of patients with eye problems agreed to see the ophthalmologist and most were seen within three days. Sufficient data for comparison were available on 1103 patients. Diagnostic agreement was found in 638 cases (58%), but potentially serious misdiagnosis was found in only 15 cases; management in three of these cases would have ensured later identification. Most commonly confused conditions were infective and allergic conjunctivitis, blepharitis, and dry eyes. General practitioners assessed visual acuity in only 114 cases yet eight of the 15 patients seriously misdiagnosed had reduced acuity, an important diagnostic sign.
Most ophthalmic disease seen in general practice does not require specialised equipment for diagnosis. Most cases of misdiagnosis have no serious consequences for the patient. Undergraduate and postgraduate training in ophthalmology should ensure that common conditions can be easily differentiated and more serious conditions identified and referred.
In recent years attention has been paid to meibomian gland dysfunction (MGD) as a distinct clinical entity responsible for chronic symptoms and signs and occurring independently or in association with atopy, cicatrising mucosal disorders and rosacea. Attempts to correlate MGD with microbiological and lipid biochemical changes are confounded by the absence of a clear descriptive language for the disorder and its associated changes. Such a language is crucial for the conduct of cross-sectional and natural history studies and therapeutic clinical trials. We present a comprehensive classification and grading scheme of meibomian gland disease, supporting our observations with illustrations.
This study was performed to determine the prevalence of Meibomian gland dysfunction (MGD) and to determine which patient profile factors might be associated with the syndrome. Patients were randomly selected, apparently normal patients presenting for routine vision examinations. Of the 398 patients for whom Meibomian gland expression was performed and a detailed history obtained, 155 patients or 38.9% exhibited MGD based on the principal clinical criterion of an absent or cloudy Meibomian gland secretion upon expression. Patient profile factors of gender, age, allergy occurrence, and contact lens wear were analyzed for correlation with MGD. Age was found to be the only significant correlating factor (positive correlation, p less than 0.0001).
A 16-year-old girl presented with contact lens intolerance. She was found to have a marked deficiency of meibomian glands in the upper lids and almost total absence in the lower lids. Evidence of tear film instability was found and attributed to deficient lid oil production. A daily wear soft contact lens was later fitted and tolerated.
Anterior blepharitis affects the lash-bearing region of the lids. It may be seborrhoeic or non-seborrhoeic and is associated with an increased prevalence of lid commensals. Colonization with S. aureus, although not necessarily associated with blepharitis, increases the risk and may be accompanied by lid crusting, collarettes, styes, and folliculitis. Enhanced cell-mediated immunity to S. aureus may provide a partial explanation for the folliculitis. S. aureus carriage is very high in atopes, while ulcerative blepharitis is associated with Candida superinfection. There is a strong link between anterior blepharitis and skin diseases such as seborrhoeic dermatitis, acne rosacea, atopy, and psoriasis.
Posterior blepharitis is usually due to obstructive meibomian gland disease resulting from hyperkeratinization of the meibomian ducts, or from cicatricial events. The latter may dominate the picture in cicatrizing disorders such as trachoma. Posterior blepharitis is strongly associated with skin disorders; focal blepharitis occurs with seborrhoeic dermatitis and diffuse blepharitis with atopy and acne rosacea. Meibomian seborrhoea may be a hypersecretory disorder, although an obstructive element may explain the excess of expressible lipid; a hyposecretory form of meibomian gland disease is also a theoretical possibility. In both anterior and posterior blepharitis, constitutional features of meibomian lid composition, together with the action of lipid commensals on such lipids, may determine some features of the diseases.
The author describes the different pathological appearances of the Meibomian glands when examined under the biomicroscope, generally by transillumination, and investigates the way these may develop. This investigation is of practical interest in determining the Meibomian origin of chronic or recurrent attacks of conjunctivitis, of blepharitis or swelling of the eyelid. Observation of these glands, which are the largest of the sebaceous glands, when practised on a living subject is of theoretical interest, too. Suggesting the different ways in which lesions occur from functional or inflammatory disorders of these glands may contribute to our knowledge of their pathology and can be linked with the study of seborrhea and its consequences.
Objective To determine whether androgen receptors affect the fatty acid profiles of neutral and polar lipids in human meibomian gland secretions. Methods Meibomian gland secretion samples were obtained from both eyes of (1) women with complete androgen insensitivity syndrome, a condition characterized by dysfunctional androgen receptors, and (2) age-matched female and male controls. Samples were processed for high-performance liquid chromatography, mass spectrometry, or both and for analysis of the mass spectra of neutral and polar lipid fatty acid fragment ions by 3 different methods. Results Androgen receptor dysfunction is associated with significant alterations in the appearance of numerous molecular species in the neutral and polar lipid fractions of meibomian gland secretions. The ability to detect these differences, and to assess their nature and extent, was facilitated by the use of several analytic approaches. Sex-related differences exist in the expression of a variety of neutral and, especially, polar fatty acid products in meibomian gland secretions. Conclusions Androgens exert a significant effect on neutral and polar lipids in human meibomian gland secretions, and these hormonal effects may be mediated through androgen receptors.
Results. OAERs in the UVB wavelength band generally are higher than in the visible (13% versus 6%), display no significant variation with job category, show a seasonal effect (highest in the winter-spring (18%), lowest in the summer (10%), and intermediate in the fall (14%)), and are reduced 34% by the use of hats. In the visible wavelength band, OAERs are affected weakly by job function, although this variation is not significant, display a seasonal effect with three seasons as in the UVB, and are not affected significantly by the use of hats. In neither the UVB nor the visible portions of the spectrum did the authors find an effect on the OAER due to photophobia or eye color. Conclusions. With the authors' exposure model, the authors have at their disposal a valuable tool for exploring the relation between UVB, UVA, and visible radiation and a number of age-related eye diseases. Invest Ophthalmol Vis Sci. 1997;38:1003-1011.
We evaluated the meibomian gland function of 11 patients before and during treatment with isotretinoin (Accutane) by assessing tear osmolarity, meibomian gland morphology, tear production, rose bengal staining, and meibomian gland excreta. We found, during Accutane use, that meibomian glands appeared significantly less dense and atrophic by meibography. Excreta thickness increased from 1.7 +/- 0.9 to 3.1 +/- 1.2 (p < 0.005), and expressible excreta volume decreased from 1.52 +/- 0.68 to 1.10 +/- 0.3 (p < 0.05) (scale 1-4). We also found a significant increase in tear osmolarity from 304.9 +/- 11 to 316.3 +/- 10 mosmol/L (p < 0.005). There was no significant change in the Schirmer test during treatment. We suggest that the clinical symptoms of blepharitis during Accutane therapy are related to decreased meibomian gland function and consequent increased tear evaporation and tear osmolarity.
(C) Lippincott-Raven Publishers.
Abstract— We have developed an empirical model with which to estimate the ocular exposure in the UVB wavelength band. This model incorporates aspects of personal behavior, geographic location, season and wavelength that have been developed from population-based data. This model, in conjunction with job history interviews, allows the estimate of cumulative exposures from age 30 in our population-based study. We present data on average annual exposure by age, gender, race, education and reported photophobia. The exposures in the general population are considerably lower than exposures reported in previous works based on occupational groups. There is a statistically significant difference between males and females, with females having lower exposures. African-Americans have median exposures similar to whites. Exposures decrease with education and with reported photophobia. These data provide the basis for characterizing lifetime exposure for the general population. The variability of exposure is much greater than found in occupational groups and includes numbers in the lowest exposure. The model should permit determination of a dose response relationship with eye disease, even to the lower dose ranges.
In order to gain information about the thickness of the oily layer of the precorneal film, a clinical method of measuring the reflectivity of the precorneal film was developed. The method entails the use of a slit-lamp photometer to measure the reflectivity at 2 selectecd wavelengths, 500 and 700 nm, at 20° incidence. Based on a physical model of the oily layer acting as a thin dielectric film, a theory is given on the interpretation of the results in terms of the thickness of the oily layer. In 10 normal subjects a mean reflectivity (+ SD) of 4.06% (+0.83) and 3.16% (+0.79) was found at 500 and 700 nm, respectively. A significant positive correlation between the measurements at the 2 wavelengths was found. It is shown, that these results are consistent with a thickness of about 40 nm, as being the most probable thickness of the oily layer. This value seems to be in accordance with other experimental data. Objective reflectometry may provide an important new tool for the study of the anteriormost part of the ocular surface.
Over the last few years the number of patients with chronic bilateral blepharitis has increased dramatically. From January 1985 until the end of 1989, a total of 407 patients with this diagnosis underwent ophthalmological and dermatological investigations at our out-patient clinic. Keratoconjunctivitis sicca (KCS) in conjunction with blepharitis occurred in 14.5% of the patient population who also suffered from acne rosacea. A comparison of the spectrum of microorganisms that have previously been isolated from affected sites with data obtained in the present study revealed that the range of microorganisms associated with this chronic localized inflammation has apparently shifted in recent years. The prevalence of Staphylococcus aureus, which was considerable in the pre-antibiotic era, has markedly decreased, although a distinct entity of staphylococcal blepharitis seems to remain, either alone or in combination with seborrheic blepharitis (62.8% of our patients). The clinical picture, microbiological findings and therapy for this condition are presented.
Background. Ocular symptoms occur in approximately 10% of patients with psoriasis vulgaris.
Patient. We report the clinical course of a 35-year-old male patient with obstructive meibomian gland dysfunction, keratoconjunctivitis and reduced reflex secretion of both eyes. Psoriasis vulgaris and hypothalamic hypogonadism were also present. Genetic testing (cytogenetic and DNA analysis) was performed because of additional facial dysmorphia, brachydactylia and obesity. No chromosomal anomaly was found and no genetic syndrome has yet been diagnosed. The therapeutic regimen included preservative-free artificial tears, occlusion of the puncta and a systemic dose of doxycycline. Dermatological symptoms were treated topically and the hypogonadism was treated with intramuscular injections of testosterone.
Conclusion. Lacrimal and meibomian glands are influenced by androgens. Therefore hormonal dysfunction can also have contributed to the blepharokeratoconjunctivitis in this patient.
The rate of water evaporation from the tear film depends on the conditions under which it is determined. If measured in a controlled and easily reproducible setting, tear evaporation rate could serve as a useful diagnostic and research tool. We have developed a tear evaporimeter that provides a non-invasive method for evaluating water evaporation rate in eyes with normal or pathologic tear films. The subject is fitted with a pair of swimmer's goggles modified so that the air over the test eye is conditioned to a desired baseline of relative humidity (29·5%) and temperature (23 ± 1°C). To eliminate other sources of water, the lids and skin under the goggles are covered with petroleum jelly. The subject is asked to keep his/her eye open and to avoid blinking during the 1-min test. The increase in relative humidity due to water evaporation from the tears is then determined. The surface area of the eye exposed to evaporation is calculated from the lid aperture.We measured the water evaporation rate in 52 normal eyes (average = 4·07 × 10−7 ± 0·40 × 10−7 g/cm2/sec) and compared the results with values obtained in 52 eyes with various tear-film abnormalities (average = 8·17 × 10−7 ± 2·65 × 10−7 g/cm2/sec). The difference between the two groups is statistically significant (P < 0·01). In normal eyes, after the instillation of one drop of 0·5% proparacaine, the increase in evaporation rate was statistically significant.
The rate of evaporation from the surface of the rabbit's eye was investigated by following changes in its corneal thickness. Normally, the cornea remains unchanged if it is exposed to the air without any possibility of the tear film being replaced. If, however, the surface of the eye is washed with saline the cornea will begin to dry rapidly. By filling the anterior chamber with oil the rate at which water evaporated from the corneal surface could be estimated. It was found to be 6 μl hr−1 for the untouched eye and 100 (μl hr−1 when the surface had been washed.The structure which normally prevents evaporation is a superficial oily layer over the tear film. It was found experimentally to be derived entirely from the Meibomian glands. The epithelium offers a negligible barrier to evaporation.
A 27-year-old woman with the syndrome characterized by ectrodactyly, ectodermal dysplasia, and cleft lip-palate had an absent lacrimal punctum in each eye, with signs and symptoms of nasolacrimal obstruction during childhood. Examination disclosed bilateral corneal vascularization and opacification, with diffuse superficial punctate staining of the ocular surface epithelium by fluorescein, an instantaneous tear film break-up time, and normal Schirmer tear measurements. A full-thickness biopsy specimen of the eyelid confirmed the absence of meibomian glands that had been suspected because of absent meibomian gland orifices and secretions. The total absence of meibomian gland secretions in this patient may be a primary feature of this case and may contribute to a lipid-deficient and unstable tear film with resultant desiccation and destruction of the ocular surface epithelium. Breakdown of the corneal epithelium in association with obstruction and infection of the nasolacrimal system may be a particularly disastrous combination for the cornea that resulted in the recurrent, severe bacterial corneal ulcers found in our patient.
Poisoning by polychlorinated biphenyl(s) (PCB) in humans leads to cutaneous and ocular findings. A white, cheeselike secretion issuing from the orifice of the Meibomian gland duct when the eyelid is squeezed is one sign of this intoxiation. In the rhesus monkey, abnormal hyperkeratosis of the ductal epithelium was observed histopathologically.
We evaluated, dermatologically and ophthalmologically, 26 patients who had chronic blepharitis (meibomitis); we also investigated 26 age- and sex-matched controls. All of the blepharitic patients had an abnormality of sebaceous gland function ranging from seborrhea sicca to seborrheic dermatitis or acne rosacea, suggesting a generalized sebaceous gland dysfunction that included the meibomian glands. Sebaceous gland abnormalities most frequently involved the cool areas of the face or scalp. Stagnation of the meibomian glands presumably caused a defect in the tear lipid layer; this resulted in an unstable tear film that produced superficial punctate keratopathy. The break-up time was much lower in these patients than in controls. The break-up time returned to normal or super-normal levels when fresh meibomian secretions were expressed into the tear film. The superficial punctate keratopathy had the characteristics of those seen in conditions with a known unstable tear film and not of those experimentally produced by staphylococcus toxin.
Blepharoconjunctivitis developed as a side-effect of treatment of patients with basal cell carcinomas, keratinizing dermatoses, and cystic acne with oral 13-cis-retinoic acid. Forty-two of the 97 dermatologic patients had signs and symptoms of blepharoconjunctivitis that were dose related and abated one week after discontinuation of the medication. About half of the patients had a history of similar symptoms prior to treatment. Staphylococcus aureus was present in eye cultures of 73% to 79% of the patients, whether symptomatic or not. Patients whose clinical appearance was that of staphylococcal blepharoconjunctivitis and whose cultures grew S aureus were successfully treated with topical erythromycin ointment to the lids even while being treated with the 13-cis-retinoic acid.
The conditions of tear film formation and stability are governed by the surface chemical characteristics of the tear film system and by the proper functioning of the lacrimal apparatus. The tear film has to remain continuous between blinks in order to fulfill it function. The presence of an abnormal tear film results in dry eye states that can be detrimental to vision. The diagnostic tests presently available are limited mainly to approximately determining tear secretion rate and estimating epithelial damage by staining techniques. The only test that directly measures tear film stability is one which determines tear film breakup time. The treatment modalities depend on the type of irregularity causing the dry eye state and range from the application of artificial tear substitutes or the obstruction of the puncta to surgical alterations of the lacrimal system.
Reflecting colours from the fatty layer of the precorneal film have been studied using mat filter (grease-proof paper, parchment paper, tracing paper) in front of the slit lamp mirror, maximally open light slit in a half-lit room, and magnification × 15. The palpebral fissure was narrowed until occurrence of red interference colour (2000 Å).
In 206 normal eyes the fatty layer was 102 ± 3 nm (±SEM), or about 0.1 μm, independent of age, sex and BUT (break up time). Maximum on awakening. Coefficient of variation 12.7 per cent.
An increased fatty layer was noticed in cases of blepharitis (129±8 nm), in 91 per cent wearing hard contact lenses and 73 per cent wearing soft contact lenses.
The fatty layer was likewise seen to be augmented in patients with acute infectious conjunctivitis (193±3 nm), chronic infectious conjunctivitis (164±7 nm), and in all states complicated by bacterial infection.
The fatty layer is normal in allergic and chronic simple conjunctivitis. Silicone oil was found to effect reduction of the fatty layer.
Since 1968, many patients have been registered as suffering from chronic chlorobiphenyl poisoning in the western part of Japan. 147 Registered patients (male 67 and female 80) with this disease were re examined in a follow up study in January 1975. Hypersecretion of the Meibomian gland and abnormal pigmentation of the conjunctiva, which are the main ocular signs of the disease, had improved.
A total of 50 patients suffering both from atopic skin disease and different clinical forms of blepharitis have been included in this study. Microbiological investigations (for bacteria and fungi) of the lid margins were performed in all cases. In 21 (42%) of the patients an ulcerative blepharitis which heavily involved the follicles of the lashes was diagnosed. The remaining 29 cases presented with blepharitis of the squamous type. The cultures revealed that 19 of the 21 patients with ulcerative blepharitis were found to grow Candida species, whereas fungi could not be detected in any of the other cases of blepharitis. The frequencies of concomitant bacterial organisms found in the cultures were similar in both groups. As atopic patients are known to exhibit a defect in their cell-mediated immunity and possibly also a defective IgA antibody response it is a widely accepted assumption that these immunological changes are contributing factors to the development of a localised inflammation of the lids which is initiated by a variety of micro-organisms. We postulate that when Candida species happen to coincide with severe inflammation in atopic patients a blepharitis of the ulcerative type will develop or deteriorate thereby implying that these microorganisms may play an important role in the development or deterioration of this severe chronic inflammation. It is therefore advisable to perform repeated scrapings and cultures in every case of recalcitrant blepharitis.
In this prospective pilot study we saw 42 consecutive giant papillary conjunctivitis (GPC) patients (80 eyes), all of whom were found to have some meibomian gland dysfunction blepharitis. Severity of GPC at presentation correlated with severity of meibomian gland dysfunction blepharitis (Kendall's tau b averaged 0.246 across the adjusted statistical analyses). Thirty-two patients (63 eyes) were refit after treating meibomian gland dysfunction blepharitis. Twenty-eight of these patients (55 eyes; 87%) continue to wear contact lenses, maintaining an improvement in GPC (mean follow-up 21 months; range 11-36 months). We hypothesize that meibomian gland dysfunction blepharitis may play a role in the pathogenesis of GPC and suggest that a large, controlled, multi-observer study be performed to further investigate this possible association.
A simple method was developed to measure tear evaporation. A sensor was inserted into a chamber covering the eye. The humidity inside each chamber then was measured every 10 sec for 2 min with both eyes either closed or open but allowing normal blinking. The difference between these conditions represented evaporation from the ocular surface. Using this method, the tear evaporation rate at 40% ambient humidity (TEROS 40) was calculated. The average TEROS 40 in normal subjects (n = 43) was 15.6 +/- 3.8 x 10(-7) g/sec. It was 9.5 +/- 5.6 x 10(-7) g/sec in patients with dry eye symptoms (n = 72, P less than 0.001). The insertion of lacrimal collagen implants in one group of such patients (n = 10) increased the TEROS 40 from 10.2 +/- 5.5 x 10(-7) g/sec to 18.2 +/- 4.8 x 10(-7) g/sec (P less than 0.01). The instillation of eye drops increased the TEROS 40 significantly in patients with dry eye symptoms for at least 1 min (n = 10, P less than 0.01); a continued effect depended on the type of eye drop. Increased TEROS 40 still was observed 5 min after instillation of viscous eye drops (0.1% and 0.3% sodium hyaluronic acid); the TEROS 40 returned to original levels within 5 min after instillation of artificial tears of normal viscosity with or without 0.05% sodium hyaluronate. In all cases, TEROS 40 returned to original levels within 10 min. This was a quick reliable method for measuring tear evaporation from the ocular surface, and it can be applied to evaluate tear dynamics and subclassifications of dry eyes.
We examined 42 contact lens-wearing patients for clinical evidence of giant papillary conjunctivitis and for meibomian gland dysfunction with gland dropout. Fifteen patients were free of clinical signs and symptoms of giant papillary conjunctivitis, whereas 27 had clinical symptoms and evidence of giant papillary conjunctivitis. Patients with giant papillary conjunctivitis had significantly more gland dropout with an average of 0.6 +/- 1.2 gland absent in both lower eyelids compared with 0.2 +/- 0.4 gland absent in patients without giant papillary conjunctivitis. Additionally, the viscosity of meibomian gland excreta was greater in the giant papillary conjunctivitis group. There was no difference in tear osmolarity or in the Schirmer test results between the two groups. These results indicated patients with giant papillary conjunctivitis were more likely to have meibomian gland dysfunction with gland dropout than patients without giant papillary conjunctivitis.
Hyperkeratinization of meibomian glands has been postulated to cause gland dysfunction. Recent investigations on rabbits show that keratin proteins are indeed present in the meibomian fluids of these animals. In this report we present our findings on the presence of these water-insoluble proteins in human meibomian secretions. 6 anti-cytokeratin antibodies, CK8, 18, 19, CK7, CK8, CK14, CK19 and AE1/AE3 were used against the keratin proteins expressed from the human meibomian fluids. Using the immunoblotting (dot blot) technique, abnormal waxy meibomian fluids obtained from subjects diagnosed to have meibomian gland dysfunction (MGD) were compared to normal clear meibomian fluids. The results show that keratins are present in a higher concentration (10%) in the abnormal human meibomian excreta as compared to the normals. Even though the presence of protein markers for keratinization in the abnormal meibomian excreta were not shown, the increased presence of keratin proteins in the abnormal meibomian fluids suggests that, in MGD patients, hyperkeratinization of ductal epithelium may have taken place. More keratin proteins (possibly those of higher molecular weights) were produced in addition to the keratin proteins normally produced by the duct epithelium. The increased amount of keratin proteins in the abnormal meibomian fluids may be explained by the susceptibility of duct epithelium to undergo the process of hyperkeratinization as postulated by other researchers.
Over the last few years the number of patients with chronic bilateral blepharitis has increased dramatically. From January 1985 until the end of 1989, a total of 407 patients with this diagnosis underwent ophthalmological and dermatological investigations at our out-patient clinic. Keratoconjunctivitis sicca (KCS) in conjunction with blepharitis occurred in 14.5% of the patient population who also suffered from acne rosacea. A comparison of the spectrum of microorganisms that have previously been isolated from affected sites with data obtained in the present study revealed that the range of microorganisms associated with this chronic localized inflammation has apparently shifted in recent years. The prevalence of Staphylococcus aureus, which was considerable in the pre-antibiotic era, has markedly decreased, although a distinct entity of staphylococcal blepharitis seems to remain, either alone or in combination with seborrheic blepharitis (62.8% of our patients). The clinical picture, microbiological findings and therapy for this condition are presented.
We examined 57 patients with symptoms of chronic blepharitis using meibomian gland expression, meibography, tear osmolarity, and the Schirmer's test. We also performed meibography on 20 normal patients free of chronic blepharitis. We found that 42 blepharitis patients (74%) had evidence of meibomian gland loss, whereas only four of 20 normal patients (20%) had any gland dropout. We performed cluster analysis on the data from the patients with blepharitis and found that these patients tended to fall into distinct groups with clinically relevant characteristics. We also found that tear osmolarity correlated positively with gland dropout (+0.413) and negatively with excreta volume (-0.499). This study demonstrates that an objective analysis of meibomian gland function may be used to assess chronic blepharitis and define subsets of blepharitis with measurable differences. It also supports the significance of meibomian gland dysfunction on tear osmolarity and the evaporative state of the eye.
Chronic blepharitis has been a difficult disease to define either microbiologically or biochemically. Sterols from meibomian secretions of normal subjects and patients were analyzed, and important differences were observed. Based on analyses of these secretions, two significantly different (P less than 0.001) types of normal subjects were found, those with and those without cholesterol esters [Norm(CP) and Norm(CA), respectively]. All patients' secretions contained cholesterol esters. Evidence was obtained which suggests that oxysterols may control the ester cholesterol accumulation. Furthermore, only when cholesterol esters were present did wax and sterol esters containing unsaturated fatty acids accumulate. Over 90% of these unsaturated fatty acids were normal (unbranched); the rest were iso-fatty acids. Preliminary results also suggest that the ester fatty alcohols are much more complex than previously reported; seven alcohols were common to all samples analyzed. Additionally, highly oxygenated alcohols were detected, especially in the meibomian keratoconjunctivitis (MKC) disease group. The MKC samples also contained an alcohol (mass, M/Z 378) not present in any of the other samples analyzed. Based on analysis of variance and linear-regression models, it was determined that the long-chain (C20-28) fatty acids were more important in determining disease signs. Furthermore, in the MKC group, the ratio of unsaturated C18 fatty acids to cholesterol in the wax and sterol esters was significantly different (P less than 0.05) from the Norm(CP) group. The authors discuss the fact that rabbit meibomian secretions are stable, despite containing a very high percentage of ester sterols, and relate this to their high percentage of branched-chain fatty acids and low percentage of unsaturated fatty acids.(ABSTRACT TRUNCATED AT 250 WORDS)
Dysfunction of the meibomian glands resulting from contact lens wear has recently been recognized. This study shows that 30% of lens wearers develop some degree of meibomian gland dysfunction after 6 months of wear whereas only 20% of non-lens wearers have similar problem. Thirty-three per cent of the male wearers have dysfunctioning glands compared with 28% of female wearers. The incidence does not depend on the type of lenses worn. There was no detectable differences between the composition of the abnormal fluid secreted by the dysfunctioning glands and the clear fluid coming out of the normal unblocked glands, as shown by thin layer chromatography. On studying the melting point of the lipids, we found that material from abnormal glands melted at approximately 3 degrees C higher than the normal fluid.
The ciliary margins of the lower lids have been vital stained by the lipid-specific Sudan III powder, fluorescein 0.1% and the bottom of the lacrimal river (Marx's line) by lissamine green 1% in 100 cases. The Meibomian orifices are situated in a straight row just in front of the Marx's line in the lipid phase. With increasing age (greater than 50 years) the orifices are more often displaced and also discharge their lipid in the depth of the aqueous phase. The number averaged 21.5 in the lipid phase and 1.7 in the aqueous phase. Active orifices staining with lipid were found in 45% of all orifices in normals, independent of age, and were increased in conjunctivitis in the lipid phase. Lissamine green-stained orifices were independent of age, phase and diagnosis. The anterior edge of Marx's line may run an irregular course in elderly normals (greater than 50 years), significantly more often in conjunctivitis and blepharitis.
The rhino mouse, a single gene recessive mutation, is characterized by abnormal epidermal differentiation and maturation leading to the loss of hair at 1 month of age as well as follicular and epidermal hyperkeratoses. We evaluated the lids and corneas of nine rhino mice and their normal litter mates at various ages from 3 months to 1 year. Tissue specimens were studied by light microscopy, scanning and transmission electron microscopy as well as immunoperoxidase using a polyclonal rabbit anti-keratin antibody. At 3 months of age there was a thickening and hyperkeratinization of the palpebral epidermis which extended into and included the meibomian gland central duct. Whereas in the skin, hyperkeratinization is followed by follicular hyperkeratosis and dermal cyst formation, in the meibomian gland, ductal hyperkeratinization appeared to lead to loss of well developed acini followed by atrophy of the gland at 1 year as confirmed by immunostaining for keratin proteins. Scanning electron microscopy revealed marked plugging of the meibomian gland orifice with keratinized cells or debris in contrast to the patent orifice of the normal lid. Ocular surface changes included the presence of a whitish exudate covering the surface of the eye and increased numbers of preexfoliative corneal epithelial cells. These findings suggest that the rhino mouse may represents the first naturally occurring disorder of the meibomian gland.
Meibomian gland dysfunction (MGD) was induced in 34 albino rabbits by the twice-daily topical application of 2% epinephrine over a period of 6 months to 1 year. Seven age-matched control rabbits, not receiving epinephrine, were followed up for a similar period. All lids were evaluated pre- and post-treatment by gross clinical examination and by transillumination biomicroscopy and photography. Of the 68 rabbit lids evaluated, 56% developed signs of MGD, which ranged from plugging of the meibomian gland orifice and presence of microcysts (subclinical lesions; 30.9% of the lids) to opacification and enlargement of the glands with increasing severity (clinical lesions; 25.0% of the lids). The remaining lids (44%) remained normal. MGD did not develop in the seven control rabbits. After the development of MGD, lids were evaluated by immunofluorescent microscopy, SDS-PAGE and Western blotting using mouse monoclonal antibodies to keratin proteins. Development and progression of MGD in the rabbit appears to correlate with increasing stratification and keratinization of the meibomian gland duct epithelium. In the early stages of MGD, focal areas of epithelial hyperkeratinization were identified by immunohistochemical staining using AE2 monoclonal antibody, specific for the 56.5 kD and 65-67 kD keratin protein marker for keratinized epidermis. As the severity of MGD progressed there was progressive increase in the AE2 staining of the duct epithelium. SDS-PAGE and immunoblotting of proteins from meibomian gland excreta in chronic MGD showed a progressive increase in both the 56.5 kD and 65-67 kD keratinization protein markers during development of MGD. We conclude that hyperkeratinization of the duct epithelium leading to plugging and dilation of the meibomian gland underlies the development of MGD following topical epinephrine treatment.
The expression of keratin proteins from meibomian glands and their correlation with skin epidermal keratins were determined. Keratin proteins were localized in both human and rabbit meibomian glands by indirect immunofluorescence using mouse monoclonal antibodies AE1, AE2 and AE3, which are known to react with human epidermal keratins as well as with keratins from other sources. Keratin proteins from rabbit meibomian glands were further isolated and characterized by SDS-PAGE and immunoblot using mouse monoclonal antibodies AE1 and AE3. Meibomian glands from human and rabbit showed similar immunofluorescent staining with each monoclonal antibody. AE1 antibody, which stains human basal epithelial cells of skin, stains all duct epithelial cells in the human but only the superficial duct epithelial cells in the rabbit meibomian gland. AE2 antibody, which stains human suprabasal epithelial cells of skin and is a marker for fully keratinized epithelia, stains the suprabasal epithelial cells of the central duct and ductules in both the human and rabbit meibomian gland. AE3 antibody, which stains all human epithelial cells of skin, stains all epithelial cells of the duct and ductules, as well as the basal epithelial cells of the acinus in both the human and rabbit meibomian gland. Keratins isolated from whole rabbit meibomian glands contained a 65-67 kD and 58 kD AE3-positive, and a 56.5 kD and 50 kD AE1-positive keratin protein. Expression of 65-67 kD/56.5 kD keratin proteins, and the immunofluorescent staining of the duct epithelium by the AE2 antibody, indicate that the meibomian gland duct epithelium is committed to the process of keratinization.
To determine whether meibomian gland dysfunction can increase tear film osmolarity and produce ocular surface changes analogous to those seen with lacrimal gland disease (keratoconjunctivitis sicca [KCS]), the authors closed the meibomian gland orifices in the right eyes of 11 rabbits by light cautery and studied the changes for 20 weeks. Tear film osmolarity was increased throughout the observation period. Conjunctival goblet cell density and corneal epithelial glycogen levels declined progressively. Closure of the meibomian gland orifices thus increased tear film osmolarity in the presence of normal lacrimal gland function and caused ocular surface abnormalities similar to KCS.
Systemic administration of 13-cis-retinoic acid caused a reduction of acinar tissue in the hamster meibomian gland. Histologic examination of treated meibomian gland tissue revealed a thickening of gland ductal epithelium and a decrease in the numbers of mature lipid-laden acinar cells. Morphometric analysis showed a reduction of up to 75% in mean volume of meibomian acinar tissue from animals fed a high dose of 13-cis-retinoic acid. Clinical observations in these animals included alopecia and weight loss. Ocular complications included crusting of the eyelid margin and the external surface of the lid and erythema of the conjunctiva. The model supports previous observations by the authors that systemic 13-cis-retinoic acid affects meibomian gland structure in a laboratory animal. The ocular side effects described in this model suggest that future functional studies may yield important insights into the complex relationship between meibomian gland morphology and function, and events on the ocular surface.
The outer surface of mammalian skin and hair is covered by the lipid secretion of the sebaceous glands; in birds, this function is fulfilled by the secretion of the large uropygeal or preen gland, sebaceous glands are numerous around all body apertures, and might be modified in form or nature of secretion to suit the special conditions of these sites. Meibomian glands are found in well-developed form in mammals. They appear to be elongated sebaceous glands, embedded in the fibrous tarsal plate of upper and lower eyelids. Meibomian secretions have much in common with sebaceous lipids, and similar analytical techniques can be used for both. Many of these are similar to the techniques that are used for analysis of a variety of other biological lipids; however, the “differentness” of sebaceous-type lipids means that additional methods must be used to cope with chain branching, wax esters of high molecular weight, a variety of unusual steryl esters, complex diesters, and other unique factors.
The lower lids of 274 normal subjects have been examined in the slit-lamp for expressibility of secretion from the Meibomian glands. Secretion could be expressed from on an average 10 glands (median 11), dependent on age, decreasing with increasing age (from 14.5 glands at about the age of 20 to 7 glands above the age of 80). The expressibility was seen to be positively correlated to the thickness of the lipid layer of the precorneal film, estimated by the semiquantitative interference method. It was positively correlated to pigmentation and to ordinary greasy scales on the lid margin. The expressibility negatively correlated to retraction of the Meibomian orifices. The expressibility was found not to be correlated to elevated orifices, foam formation in the external part of the eye, cysts in the tarsus, nor with casts round the eyelashes. It is important to distinguish between cylindric casts (Demodex-induced) and ordinary greasy scales on eye lashes and lid margin.
Meibomian lipid promotes the formation and stabilisation of the precorneal tear film. The deposited layer of this material at the lid margins prevents entry into the eye of skin surface fatty acids which would disrupt the film. The external oily layer also acts to reduce the rate of evaporative loss of fluid from the tear film. The relationship between composition of the secretion and its physical properties is discussed.