Infra-red Imaging of Meibomian Glands and Evaluation of Lipid Layer in Sjogren’s Syndrome Patients. Sjogren’s Syndrome has been defined as an autoimmune disease characterized by inflammation and destruction of sweat, salivary and tear glands.
Dry eye and Sjogren’s Syndrome occurs primarly in women, particularly during or post-menopause. Although the mechanism as to why this correlation exists is not fully understood, an underlying similarity between Sjogren’s Syndrome and menopausal women is a deficiency in androgens / hormones. The androgen-deficiency may lead to destruction of oil secreting glands (meibomian glands) in the eyelids or gland loss, leading to an increase in the evaporation of the tear film and subsequently dry eye experienced by many Sjogren’s Syndrome patients.
Meibomian glands and Dry Eyes
Meibomian glands are sebaceous oil glands located in the upper and lower eyelids. There are about 30-40 glands in the upper lid and 20-30 glands in the lower lid. Tears on the surface of the eye have two functional layers, the outermost layer composed of oils. The meibomian glands function to secrete the oils of the tears onto the surface of the eye which aids in preventing quick evaporation of the tear film and subsequent discomfort felt by the eye.
Meibomian gland dysfunction (MGD) has been classified by the International Workshop on Meibomian Gland Dysfunction as a chronic, diffuse abnormality of the meibomian glands, commonly characterized by terminal duct gland obstruction and / or qualitative / quantitative changes in the glandular secretion. This may result in alteration of the tear film, symptoms of eye irritation, clinically apparent inflammation, and ocular surface disease. Meibomian gland dysfunction (MGD) has been shown to increase with age, contact lens wear, and as mentionned above, androgen deficiency. Thus, the recent findings would suggest that not only are the severe dry eye manifestations experienced in Sjogren’s syndrome due to lack of tear production, but may also be due to poor tear quality due to lack of oil layer present over the pre-ocular tear film.
Few studies have investigated meibomian gland loss in patients with Sjogren’s syndrome and to our knowledge; none have compared gland loss evaluations to the measured lipid (oil) layer thickness in thes patients. Thus, the purpose of this study was to evaluate and compare the meibomian gland drop out and the lipid layer thickness in patient with and without Sjogren’s syndrome.
Lipid Layer Thickness Evaluation
The tear film lipid layer thickness was measured for each participant using the Keeler Tearscope Plus (Broomall, USA). During evaluation, the lipid layer of for each participant would reflect a certain pattern back to the examiner. From the reflected pattern, the examiner was able to determine the thickness of the lipid layer.
Non-Invasive Tear Break-Up Time
The non-invasive tear break-up time was measured using the Atlas Corneal Topographer (Oberkochen, Germany). Tear break-up time measures how quickly the tear film evaporates off of the surface of the eye. Each participant was asked to look at the center of the concentric ring pattern displayed on the instrument screen. The ring pattern was reflected off of the participant’s tear film and viewed by the experimenter on a screen. The participant was instructed to blink 3 consecutive times and then asked to hold their eyes open for as long as they could or until the researcher asked the participant to blink. The time elapsed between the last blink and first sign of distortion occurring of the ring pattern or subsequent blink was recorded as the non-invasive tear break-up time. This was repeated a number of 3 times for each eye.
Meibomian gland loss was analyzed using an infrared camera system. Multiple images were taken of the upper and lower eyelids of both eyes for each participant. Gland loss-out was first evaluated subjectively using a grading scale of 0-3 based on the grading system created by Arita et al. with grade 0 = no gland loss; grade 1 = areas of gland loss were less than 33% of total gland area; grade 2 = area of gland loss was between 33% and 67% of total area; grade 3 = area of gland loss was greater than 67%. Scores were for the upper and lower eyelids were summed to obtain a score for each eye.
Meibography images were also analysed using a computer software programme (ImagJ, National Institute of Health). Total area of the eyelid where glands should be present was calculated and the area that still had glands present was calculated. The gland area value was then subtracted from the total area and converted to a percent of area that had gland loss.
The investigator was not aware as to whether the participant had Sjogren’s syndrome or not during the subjective and digital analysis of gland loss.
There were 10 participants without Sjogren’s syndrome enrolled in the study (3 male and 7 females) with an average age of 58.5 years. 11 participants with Sjogren’s Syndrome were enrolled (1 male and 10 females) with an average age of 56.0 years. Not one participant in the control group reported the use of artificial tear drop and all 11 participants in the Sjogren’s group reported use of artificial tear drops.
All of the participants in the Sjogren’s group had been diagnosed with Sjogren’s syndrome for at least 4 years, the earliest diagnosis in the group being 1999 and the latest being 2008. All participants also reported that dry eye symptoms preceded diagnosis with Sjogren’s syndrome.
Tear evaporation was approximately 4x quicker in the participants with Sjogren’s syndrome compared to the participants without Sjogren’s. The Lipid layer thickness was also significantly reduced in the participants with Sjogren’s compared to those without Sjogren’s syndrome.
Subjective gland loss were different for the upper right eyelid and lower left eyelid with the scores in the Sjogren’s syndrome group being higher indicating more loss of the glands. There was little difference in subjective gland loss for the lower lid of the right eye and the upper lid of the left eye. Digital grading scores showed significant difference in gland loss values between the control and Sjogren’s syndrome groups for the upper lid of the right and left eye and the lower lid of the left eye, again with the Sjogren’s group exhibiting higher degree of gland loss than the control group. There was no significant difference between the digital gland loss scores between groups in the lower right lid.
In this study, the participants in the Sjogren’s syndrome group presented with a significantly thinner lipid layer, with the majority of the lipid layers being relatively thinner than the group of participants without Sjogren’s syndrome. The Sjogren’s group also had a shorter non invasive tear break-up time which could be attributed to the thinner lipid layer thickness leading to quicker evaporation of the tear film.
The shorter tear break-up time and thin lipid layer thickness found in the Sjogren’s group could be further explained by the higher degree of gland loss found in the Sjogren’s syndrome group. As mentionned previously, the meibomian glands secrete the lipid layer of the tears, thus if there are fewer glands present, not as much lipid would be secreted, leading to a thinner lipid layer and short tear break-up time.
In conclusion, this study supports previous work suggesting that meibomian gland dysfunction plays an essential role in the severe dry eye experienced by patients with Sjogren’s syndrome. It also exemplifies the use of meibography for a quick and easy assessment of the degree of gland dropout in patients with Sjogren’s syndrome which could aid in a better understanding and management of the disease.