MEIBOMIAN GLAND DYSFUNCTION & DRY EYE : WHAT DO THE EXPERTS SAY ?

Alan G. Kabat, OD, FAAO
(901) 252- 3691 Memphis, Tennessee  [email protected]

Course description: This course reviews the latest thoughts, theories and management strategies for meibomian gland dysfunction (MGD), which is now thought to be the most significant cause of evaporative dry eye.

LEARNING OBJECTIVES: At the conclusion of this lecture, the attendee will be able to:

1. Recognize the various clinical manifestations of blepharitis and meibomian gland dysfunction; 2. Understand the impact of the aforementioned conditions on the function and integrity ocular surface and tear film; 3. Identify the newest and best treatment modalities for managing chronic lid margin disease and evaporative dry eye.

Dry Eye Defined:

Dry eye is a multifactorial disease of the tears

and ocular surface that results in symptoms of discomfort, visual disturbance, and tear film instability with potential damage to the ocular surface. It is accompanied by increased osmolarity of the tear film and inflammation of the ocular surface.

The definition and classification of dry eye disease: Report of the Definition and Classification Subcommittee of the International Dry Eye WorkShop (2007). Ocul Surf. 2007 Apr;5(2):75-92.

Aqueous Deficient Dry Eye : implies that dry eye is due to a failure of lacrimal tear secretion.

Evaporative Dry Eye : is due to excessive water loss from the exposed ocular surface in the presence of normal lacrimal secretory function. Its causes have been described as intrinsic , where they are due to intrinsic disease affecting lid structures or dynamics, or extrinsic , where ocular surface disease occurs due to some extrinsic exposure.

Causes of Dry Eye • ADDE: − Sjögren Syndrome − Non-Sjögren Syndrome, e.g.  Age-related lacrimal gland deficiency  Congenital Alacrima  Lacrimal Gland Infiltration, Ablation or Denervation  Obstruction of Lacrimal Gland Ducts  Reflex Hyposecretionn • EDE: − Intrinsic  Meibomian Gland Dysfunction  Disorders of Lid Aperture and Lid/Globe Congruity  Low Blink Rate − Extrinsic  Ocular Surface Disorders • Vitamin A Deficiency • Topical Drugs & Preservatives (e.g. BAK)  Contact Lenses  Allergic Eye Disease

Meibomian Gland Dysfunction Defined:

Meibomian gland dysfunction (MGD) is a chronic, diffuse abnormality of the meibomian glands, commonly characterized by terminal duct 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.

Nelson JD, Shimazaki J, Benitez-Del-Castillo JM, et al. The international workshop on meibomian gland dysfunction: report of the definition and classification subcommittee. Invest Ophthalmol Vis Sci. 2011 Mar 30;52(4):1930-7.

“Overall, MGD is an extremely important condition, conceivably underestimated,

and very likely the most frequent cause of dry eye disease.” Nichols KK, Foulks GN, Bron AJ, et al. The international workshop on meibomian gland dysfunction: executive summary. Invest Ophthalmol Vis Sci. 2011 Mar 30;52(4): 1922 -9. Types of Blepharitis • Anterior − Bacterial / “ Staph ” − Seborrheic • Posterior − Clinically synonymous with Meibomian Gland Dysfunction (MGD) − Obstruction of meibomian ducts with associated inflammation of the lid margins − Secondary effects include compromised tear film

Meibomian Gland Dysfunction: Pathophysiology • Results from hyperkeratinization of ductal epithelium within meibomian glands • Leads to increased intraductal pressure and stagnation of normal meibum flow • Obstruction of meibomian ducts causes accumulation and thickening of lipids, bacterial colonization and inflammation of the lid margins • Secondary effects include compromised tear film & associated dry eye pathology

Diagnosis:

• Clinical symptoms − Burning, foreign body sensation, itching… consistent with dry eye − Unstable or intermittently blurred vision − Symptoms often worse after awakening; may improve with heat and/or massage

• Clinical signs: − “Foamy” or “frothy” tears − Inspissated orifices (“capped glands”) − Gland expression  turbid, thickened or “toothpaste-like” secretions − Thickened, “bumpy” lid margins & lid margin telangiectasis

Dry Eye Treatment Options • ADDE: − Environmental modifications − Tear replacement therapy (i.e. artificial tear drops, gels & ointments) − Immunomodulatory / anti-inflammatory agents (e.g. cyclosporine, steroids) − Secretagogues (?) − Nutritional support (e.g. flax-seed / omega-3 supplementation) − Punctal occlusion − Autologous serum − N-Acetylcysteine − Moist chamber goggles • EDE − Lid hygiene (i.e. “lid scrubs”) − Lid hyperthermia (i.e. warm compresses) & digital massage − Topical antibiotic (e.g. erythromycin) − Topical corticosteroid − Nutritional support (e.g. flax-seed / omega-3 supplementation) − Oral tetracycline drugs

MGD Treatment

• Rationale: 1. Diminish ocular surface friction 2. Restore the normal chemistry, consistency and flow of meibum 3. Reduce ocular surface inflammation

• Historical / Conventional Therapies: 1. Support the (lipid aspect of the) tear film 2. Lid hygiene (i.e. “lid scrubs”) 3. Lid hyperthermia (i.e. warm compresses) & massage 4. Topical corticosteroid – usually in combination with antibiotic (e.g. TobraDex) 5. Nutritional support (e.g. flax-seed / omega-3 supplementation) 6. Oral tetracycline drugs (especially low-dose doxycycline)

• Newer & experimental therapies − Topical cyclosporine-A (Restasis) - off-label use for blepharitis − Topical azithromycin 1% (AzaSite ®) - off-label use for blepharitis − N-acetylcysteine − Meibomian gland probing (Maskin technique) − Automated thermodynamic manipulation of glands

REFERENCES / RECOMMENDED READING LIST:

− Behrens A, Doyle JJ, Stern L, et al. Dysfunctional tear syndrome: A delphi approach to treatment recommendations. Cornea. 2006;25(8):900-907. − 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 Feb;25(2):171-5. − Lemp M, Nichols K. Blepharitis in the United States 2009: A survey-based perspective on prevalence and treatment. Ocul Surf. 2009 Apr;7(2 suppl):S1-14. − Foulks GN, Borchman D. Meibomian gland dysfunction: the past, present, and future. Eye Contact Lens. 2010 Sep;36(5):249-53. − Luchs J. Efficacy of topical azithromycin ophthalmic solution 1% in the treatment of posterior blepharitis. Adv Ther. 2008 Sep;25(9):858-70. − Haque RM, Torkildsen GL, Brubaker K, et al. Multicenter open-label study evaluating the efficacy of azithromycin ophthalmic solution 1% on the signs and symptoms of subjects with blepharitis. Cornea. 2010 Aug;29(8):871-7. − Foulks GN, Borchman D, Yappert M, et al. Topical azithromycin therapy for meibomian gland dysfunction: clinical response and lipid alterations. Cornea. 2010 Jul;29(7):781-8. − Blackie CA, Korb DR, Knop E, Bedi R, Knop N, Holland EJ. Nonobvious obstructive meibomian gland dysfunction. Cornea. 2010 Dec;29(12):1333-45. − Korb DR, Blackie CA. Restoration of meibomian gland functionality with novel thermodynamic treatment device-a case report. Cornea. 2010 Aug;29(8):930-3. − Opitz DL, Tyler KF. Efficacy of azithromycin 1% ophthalmic solution for treatment of ocular surface disease from posterior blepharitis. Clin Exp Optom. 2010 Nov 17. [Epub ahead of print] − Maskin SL. Intraductal meibomian gland probing relieves symptoms of obstructive meibomian gland dysfunction. Cornea. 2010 Oct;29(10):1145-52. − Akyol-Salman I, Azizi S, Mumcu U, Baykal O. Efficacy of topical N-acetylcysteine in the treatment of meibomian gland dysfunction. J Ocul Pharmacol Ther. 2010 Aug;26(4):329-33. − Viso E, Gude F, Rodríguez-Ares MT. The association of meibomian gland dysfunction and other common ocular diseases with dry eye: a population-based study in Spain. Cornea. 2011 Jan;30(1):1-6. − Nichols KK. The international workshop on meibomian gland dysfunction: introduction. Invest Ophthalmol Vis Sci. 2011 Mar 30;52(4):1917-21. − Nichols KK, Foulks GN, Bron AJ, et al. The international workshop on meibomian gland dysfunction: executive summary. Invest Ophthalmol Vis Sci. 2011 Mar 30;52(4):1922-9. − Nelson JD, Shimazaki J, Benitez-Del-Castillo JM, et al. The international workshop on meibomian gland dysfunction: report of the definition and classification subcommittee. Invest Ophthalmol Vis Sci. 2011 Mar 30;52(4):1930-7. − Knop E, Knop N, Millar T, et al. The international workshop on meibomian gland dysfunction: report of the subcommittee on anatomy, physiology, and pathophysiology of the meibomian gland. Invest Ophthalmol Vis Sci. 2011 Mar 30;52(4):1938-78. − Green-Church KB, Butovich I, Willcox M, et al. The international workshop on meibomian gland dysfunction: report of the subcommittee on tear film lipids and lipid-protein interactions in health and disease. Invest Ophthalmol Vis Sci. 2011 Mar 30;52(4):1979-93. − Schaumberg DA, Nichols JJ, Papas EB, et al. The International Workshop on Meibomian Gland Dysfunction: Report of the Subcommittee on the Epidemiology of, and Associated Risk Factors for, MGD. Invest Ophthalmol Vis Sci. 2011 Mar 30;52(4):1994-2005. − Tomlinson A, Bron AJ, Korb DR, et al. The international workshop on meibomian gland dysfunction: report of the diagnosis subcommittee. Invest Ophthalmol Vis Sci. 2011 Mar 30;52(4):2006-49. − Geerling G, Tauber J, Baudouin C, et al. The international workshop on meibomian gland dysfunction: report of the subcommittee on management and treatment of meibomian gland dysfunction. Invest Ophthalmol Vis Sci. 2011 Mar 30;52(4):2050-64. − Asbell PA, Stapleton FJ, Wickström K, et al. The international workshop on meibomian gland dysfunction: report of the clinical trials subcommittee. Invest Ophthalmol Vis Sci. 2011 Mar 30;52(4):2065-85.