|Year : 2018 | Volume
| Issue : 3 | Page : 163-169
Management options for Meibomian gland dysfunction
Sally E Salloom, Molham A ElBakary, Amr M Awara, Osama E Shalaby
Department of Ophthalmology, Faculty of Medicine, Tanta University, Tanta, Egypt
|Date of Submission||07-Jan-2018|
|Date of Acceptance||15-Mar-2018|
|Date of Web Publication||24-Sep-2018|
Amr M Awara
Department of Ophthalmology, Faculty of Medicine, Tanta University, Tanta 31111
Source of Support: None, Conflict of Interest: None
Background Meibomian gland (MG) dysfunction is a chronic, diffuse abnormality of the MGs. At the end stage, it is characterized by terminal duct obstruction and/or qualitative/quantitative changes in the glandular secretions. This may result in alterations of the tear film.
Patients and methods This is a prospective randomized study that included two groups of patients;, with 40 eyes in each group. The first group (group I) received oral azithromycin for 5 days (500 mg in the first day and then 250 mg/day for 4 days), whereas the second group (group II) received oral doxycycline for 1 month (100 mg/twice daily). The patients were evaluated by the symptoms, signs, and special tests (Schirmer’s and tear break-up time tests) of dry eye. The patients were followed up at two main visits: at day 12 and at day 36 from the start of therapy.
Results There was no significant difference between group I and group II regarding age, sex, or presence of diabetes mellitus. At the first post-treatment visit, group I had significant improvement in itching (P=0.002), foreign body sensation (P=0.001), and ocular surface staining (P=0.01) compared with group II. At the second post-treatment visit, group I had significantly better results regarding foreign body sensation (P=0.05), eyelid swelling (P=0.04), and ocular surface staining (P=0.03).
Conclusion Both oral azithromycin and oral doxycycline had beneficial effects in patients with MG dysfunction. Azithromycin group was proved to have better results regarding symptoms, signs, and special tests with lower rates of adverse effects.
Keywords: azithromycin, doxycycline, dysfunction, management, Meibomian gland
|How to cite this article:|
Salloom SE, ElBakary MA, Awara AM, Shalaby OE. Management options for Meibomian gland dysfunction. Delta J Ophthalmol 2018;19:163-9
|How to cite this URL:|
Salloom SE, ElBakary MA, Awara AM, Shalaby OE. Management options for Meibomian gland dysfunction. Delta J Ophthalmol [serial online] 2018 [cited 2019 Mar 23];19:163-9. Available from: http://www.djo.eg.net/text.asp?2018/19/3/163/242145
| Introduction|| |
Meibomian gland More Details dysfunction (MGD) is a common disease that may involve inflammation, hypersecretion, and abnormal excretion of the gland . This can cause alteration in tear film, leading to evaporative type of dry eye . MGD can be classified into two major types: high delivery and low delivery .
Obstruction of Meibomian glands (MG) secondary to hyperkeratinization of the duct epithelium and accumulation of meibum results in gland inflammation and maybe increase in bacterial colonization . MGD may be asymptomatic and can only be detected by gland expression or more frequently by the symptoms of dry eye .
Foreign body (FB) sensation, burning sensation, red eye, excessive tearing, and photophobia are the commonest symptoms of MGD . The signs include loss of clarity and thickening of expressed meibum, pouting or plugging of MG orifices, MG drop-out which can be detected by meibography, increased thickness and vascularity of eyelid margin, loss of the eye lashes, trichiasis, and vascular invasion .
Conservative treatment is usually sufficient in most patients. This includes warm compresses, eyelid massage and cleansing with baby shampoo, and the use of artificial tears to maintain the ocular surface well lubricated ,. However, in severe and refractory cases to conservative treatment, antibiotics (topical and systemic) that have anti-inflammatory properties will be required ,.
| Patients and methods|| |
This is a randomized controlled study that included 40 patients having MGD who were recruited from the Outpatient Clinic of Tanta University Hospital during the period from January 2016 to June 2016. The inclusion criteria were plugging of MG orifices, dimpling of posterior lid margin, thickening and increased vascularity of the lid margin, and abnormal position of mucocutaneous junction. Preadolescent patients, patients with ocular cicatricial pemphigoid, hepatic disease, pregnant or lactating women, patients with altered lid anatomy for any reason, and patients with intraocular diseases (e.g. glaucoma) were excluded from the study.
All the patients were subjected to the following:
- Full history taking including age, sex, and symptoms of ocular discomfort. Four main symptoms were measured on a four-point categorical scale:
- Itching: grade 0=none, grade 1=awareness, grade 2=desire to rub, and grade 3=frequent rubbing.
- Burning: grade 0=none, grade 1=awareness, grade 2=desire to rub, and grade 3=frequent rubbing.
- FB sensation: grade 0=none, grade 1=awareness, grade 2=desire to rub, and grade 3=frequent rubbing.
- Eyelid swelling: grade 0=none, grade 1=noticeable, grade 2=obvious, and grade 3=decrease to palpebral fissure.
- Full ophthalmological examination including slit-lamp examination to assess and record the severity of the main signs on a four-point categorical scale:
- Lid margin morphological changes:
- Plugging of MG orifices: grade 0=none, grade 1=less than 1/3 of the MG orifices, grade 2=between 1/2 and 2/3, and grade 3=more than 2/3.
- Notching of posterior lid margin, which was graded as follows: grade 0=none, grade 1=less than 1/3 of the posterior lid margin, grade 2=between 1/2 and 2/3, and grade 3=more than 2/3.
- Gland expression was performed (digital pressure) on the central third of lower eyelid and graded as follows: grade 0=none, grade 1=cloudy, grade 2=turbid, and grade 3=solid.
- Bulbar conjunctival redness was graded based on the color of the conjunctiva on the slit-lamp as follows: grade 0=none, grade 1=pink, grade 2=light red, and grade 3=bright red.
- Tear break-up time test (TBUT) and Schirmer 1 test: the patients were graded according to these tests as shown in [Table 1].
- Tear meniscus height measurement: the height of the meniscus formed between the lower lid margin and bulbar conjunctiva was measured in millimeter using cobalt blue filter of the slit-lamp beam and was graded as less than 1 mm or greater than 1 mm.
- Ocular surface staining with fluorescein, rose bengal, and lissamine green stains.
The patients were randomly and equally assigned into two groups:
- Group I (40 eyes of 20 patients) received oral azithromycin for 5 days (500 mg at the first day and then 250 mg/day for 4 days).
- Group II (40 eyes of 20 patients) received oral doxycycline for 1 month (100 mg/twice daily).
The two groups were maintained on conservative management in the form of eyelid massage, cleaning, warm foments twice daily, and artificial tears four time daily.
The first follow-up visit was at day 12 (1 week after 5 days of azithromycin therapy). The second follow-up visit was at day 36 (1 month after 5 days of azithromycin therapy in group I and 1 week after 1 month of doxycycline therapy in group II).
The study was approved by the Ethical Committee of Tanta University. An informed consent was obtained from each participant before all the steps of the interview process and examination procedures with adherence to the guidelines of the declaration of Helsinki.
Data were statistically analyzed by an IBM compatible personal computer with SPSS statistical package version 23 (SPSS Inc. Released 2015. IBM SPSS statistics for windows, version 23.0; Armonk, New York, USA). χ2-Test was used to study association between qualitative variables. Whenever any of the expected cells were less than five, Fischer’s exact test with Yates correction was used. P value of less than 0.05 was considered statistically significant.
| Results|| |
The two groups did not show any significant difference regarding age, sex, or diabetes mellitus. The mean age of group I was 52.4±13.08 years and of group II was 52.10±12.4 years (P=0.95). Males represented 45.0% (nine patients) of group I and 55.0% (11 patients) of group II. Diabetes mellitus was present in five (25.0%) patients in group I and in seven (35.0%) patients in group II.
There was no significant difference between both groups regarding the symptoms, signs, or the special tests of MGD before treatment ([Table 2],[Table 3],[Table 4]).
At the first post-treatment visit, group I had significantly more improvement in itching and FB sensation than group II (P=0.002 and 0.001, respectively; [Table 5] and [Table 6]). However, the special tests used did not differ significantly between the two group except the ocular surface staining which showed better results in group I than in group II (P=0.01; [Table 7]).
At the second post-treatment visit, group I still showed significantly better results regarding FB sensation (P=0.05) and eyelid swelling (P=0.04). Ocular surface staining also showed significantly more improvement in group I than in group II (P=0.03; [Table 5],[Table 6],[Table 7]).
The occurrence of adverse effects showed no significant difference between the two groups at the first follow-up visit. However, in the second visit, nausea was significantly higher in group II (P=0.04; [Table 8]).
|Table 8 Occurrence of complications at the first and second post-treatment visits|
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Systematic comorbidities were present in 72.5% of patients with MGD. A total of 12 (30.0%) patients had diabetes mellitus, 12 (30.0%) patients had hypertension, and five (12.5%) patients had both.
| Discussion|| |
MGD is a common and chronic disorder that has a significant adverse effect on patients’ quality of life. It is a leading cause of evaporative dry eye disease, as MGs play an important role in providing lipids to the tear film, which helps to retard the evaporation of tears from the ocular surface. MGD is also often present in conjunction with primary aqueous-deficient dry eye .
The effect of MGD on the patients can be severe with negative effects on their quality of life and may even lead to a loss of productivity .
In the present study, the age of the patients ranged from 23 to 65 years, with a mean of 52.40±13.08 years in group I, and ranged from 25 to 65 years, with a mean of 52.10±12.40 years in group II, with no statistically significant difference between the two groups. In the year 2011, Nien et al.  studied the effects of age on human MGs. They recruited 86 participants with MGD with a mean age of 72 years ranging from 18 to 95 years. Their study revealed a significant positive correlation between age and MG expression grade, as older participants displayed significantly higher grades of MGD .
Sex distribution, in the current study, did not show any significant difference between the two studied groups, as group I had 45% males and 55.0% females and group II had 60% males and 40% females. A study published in the year 2014 demonstrated the association between sex and MGD. It was done by Kwan et al. , who took a sample from 122 participants (75 females and 47 males) older than 18 years (mean age: 45.7±16.3 years) and classified them as having MGD dry eye or aqueous-deficient dry eye based on the accepted tests and Ocular Surface Disease Index. Females were found to have significantly higher frequency and intensity of dryness and vision disturbances than males .
The present study revealed that 72.5% of the patients with MGD had systemic morbidities, as 30% had DM, 30% had hypertension, and 17.5% had both DM and hypertension. This agrees with Lemp , who studied the systemic diseases and their effects on the ocular surface and found that there were relations between systemic diseases and dry eye, commonly owing to autoimmune disorders, for example Sjogren’s syndrome, rheumatoid arthritis, systemic lupus erythematosus, and skin disorders like rosacea and other systemic diseases including diabetes and some medications such as antihypertensive drugs and β–blockers, which can adversely affect the tear film and lead to dry eye .
Both groups studied in this work showed marked improvement in many symptoms (itching, burning sensation, FB sensation, and eyelid swelling) and signs (MG secretions and eyelid changing plugging). At the first follow-up visit, patients of group I reported significantly lower rates of itching and FB sensation than group II. At the second follow-up visit, patients of group I still had better improvement in FB sensation than group II. In addition, eyelid swelling showed more improvement in group I than in group II patients.
Regarding the special tests used, including TBUT, Schirmer 1 test, and tear meniscus height, they did not differ significantly between the two groups. However, the ocular surface staining showed better results in group I than in group II (at all the follow-up visits). This agrees with the results of Kashkouli et al.  who compared between oral azithromycin and doxycycline in MGD. Their study included 110 patients older than 12 years with MGD who were randomly assigned to receive oral 5-day azithromycin or doxycycline for 1 month. The improvement of the symptoms was nearly equal in both groups with no significant difference between them . Igami et al. , did their study on 26 eyes of 13 patients diagnosed with posterior blepharitis. They gave the patients oral azithromycin 500 mg per day in three cycles with 7-day interval. Subjective clinical outcomes were graded and scored 1 day before and 30 days after the end of treatment based on the severity of eyelid debris, telangiectasia, lid swelling and redness, and ocular mucus secretion. They found that all the clinical outcome scoring, Schirmer test, and ocular surface staining were statistically significantly improved except for the eyelid swelling . This agrees with the results of Foulks et al. , who compared between oral doxycycline and topical azithromycin which revealed that symptoms of MGD decreased or became absent after 8 weeks of treatment with doxycycline with statistically significant reduction in itching and FB sensation and absence of burning symptoms after 8 weeks .
Comparable results were reported by Yoo et al. , who divided 300 eyes with chronic resistant MGD into three groups: first with high dose of doxycycline (200 mg/day), second group with low dose of doxycycline (20 mg/day), and third placebo group. They observed that in comparison with the placebo group, both of the first and second groups showed statistically significant improvement in TBUT and Schirmer’s test. They observed also no statistically significant difference between high and low doses of doxycycline .In the present work, there were mild gastrointestinal and dermatological adverse effects in both groups, with no statistically significant difference between them. All these adverse effects were temporary and disappeared after cessation of the medications. The same was observed by Kashkouli et al.  as they observed mild gastrointestinal adverse effects which were not significantly different between the azithromycin and doxycycline groups except for the second visit, when the doxycycline group had significantly more adverse effects .
In conclusion, both oral azithromycin and oral doxycycline had beneficial effects in patients with MGD. Azithromycin group was proved to have better effect regarding symptoms, signs, and special tests, with lower rates of the adverse effects.
This research was entirely financially supported by the authors.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Lemp MA, Foulk GN. Report of the definition and subcommittee of the international dry eye work shop. Ocul Surf 2007; 5:75–92.
Nelson JD, Shimazaki J, Benitez-del-Castillo JM, Craig JP, McCulley JP, Seika Den S, Foulks GN. The international workshop on Meibomian gland dysfunction: report of the definition and classification subcommittee. Invest Ophthalmol Vis Sci 2011; 52:1930–1937.
Nichols KK, Foulks GN, Bron AJ, Glasgow BJ, Dogru M, Tsubota K et al.
The international workshop on Meibomian gland dysfunction: executive summary. Invest Ophthalmol Vis Sci 2011; 52:1922–1929.
Lee H, Min K, Kim EK, Kim TI. Minocycline controls clinical outcomes and inflammatory cytokines in moderate and severe Meibomian gland dysfunction. Am J Ophthalmol 2012; 154:949–957.
Akyol-Salman I, Azizi S, Mumcu U, Kaykal O. Efficacy of topical N
-acetylcysteine in the treatment of Meibomian gland dysfunction. J Ocul Pharmacol Ther 2010; 26:329–333.
Perry HD, Doshi-Carnevale S, Donnenfeld ED, Solomon R, Biser SA, Bloom AH. Efficacy of commercially available topical cyclosporine A 0.05% in the treatment of Meibomian gland dysfunction. Cornea 2006; 25:171–175.
Tomlinson A, Bron AJ, Korb DR, Amano S, Paugh JR, Pearce EI et al.
The international workshop on Meibomian gland dysfunction: report of the diagnosis subcommittee. Invest Ophthalmol Vis Sci 2011; 52:2006–2049.
Romero JM, Biser SA, Perry HD, Levinson DH, Doshi SJ, Terraciano A et al.
Conservative treatment of Meibomian gland dysfunction. Eye Contact Lens 2004; 30:14–19.
Guillon M, Maissa C, Wong S. Eyelid margin modification associated with eyelid hygiene in anterior blepharitis and Meibomian gland dysfunction. Eye Contact Lens 2012; 38:319–325.
Igami TZ, Holzchuh R, Osaki TH, Santo RM, Kara-Jose N, Hida RY. Oral azithromycin for treatment of posterior blepharitis. Cornea 2011; 30:1145–1149.
Geerling G, Tauber J, Baudouin C, Goto E, Matsumoto Y, O’Brien T et al.
The international workshop on meibomian gland dysfunction: report of the subcommittee on management and treatment. Invest Ophthalmol Vis Sci 2011; 52:2050–2064.
Qiao J, Yan X. Emerging treatment options for Meibomian gland dysfunction. Clin Ophthalmol 2013; 7:179–803.
Fenga C, Aragona P, Cacciola A, Spinella R, Di Nola C, Ferreri F, Rania L. Meibomian gland dysfunction and ocular discomfort in video display terminal workers. Eye 2008; 22:91–95.
Nien CJ, Paugh JR, Massei S, Wahlert AJ, Kao WW, Jester JV. Age-related changes in the Meibomian gland. Exp Eye Res 2009; 89:1021–1027.
Kwan JT, Opitz DL, Hom MM, Paugh JR. Gender differences in a Meibomian gland dysfunction-specific symptom questionnaire. Invest Ophthalmol Vis Sci 2014; 55:22–30.
Lemp MA. Dry eye (Keratoconjunctivitis Sicca), rheumatoid arthritis, and Sjogren syndrome. Am J Ophthalmol 2005; 140:898–899.
Kashkouli MB, Fazel AJ, Kiavash V, Nojomi M, Ghiasian L. oral azithromycin versus doxycycline in Meibomian gland dysfunction: a randomized double-masked open-label clinical trial. Br J Ophthalmol 2015; 99:199–204.
Foulks GN, Borchman D, Yappert M, Kakar S. Topical azithromycin and oral doxycycline therapy of Meibomian gland dysfunction: a comparative clinical and spectroscopic pilot study. Cornea 2013; 32:44–53.
Yoo SE, Lee DC, Change MH. The effect of low-dose of doxycycline in chronic Meibomian gland dysfunction. Korean J Ophthalmol 2005; 19:258–263.
[Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6], [Table 7], [Table 8]