Dysfunction: disease process, but main issue is function of glands is disturbed, leading to instability (evaporation, increased surface tension, unsealed lids during sleep) and possible symptomsDiffuse: involves most of glands. Localized involvement (chalazion) doesn’t cause abnormalities in tear film or ocular surface, therefore not part of MGDObstruction: most prominent aspect of MGD
Hypersecretory: hyperresponse of glands to androgens is most likely explanation. Not assoc. w/ inflammation and normal appearance w/ meibography. Believed to occur is some systemic conditions such as seb dermatitis (fungus), atopy, rosaceaHyposecretory: decrease without obstruction. No published verified evidence, but assoc. clinically w/ gland atrophy. Decreased # of functional glands proportional to the duration of contact lens wear.
3. Stabilize tear film by reducing surface tension4. Enhance spreading over aqueous surface by presence of surfactant lowering surface tension. Surfactant also found in lacrimal glands, conjunctival epithelial cells, nasolacrimal system, auditory canal, lungs. More likely that the lipid layer collapses and expands with each blink than is actually re-spread with each blink.
EDES and ADDES are not mutually exclusive and symptoms do not necessarily specify a subtype of dry eye
UL tarsal plate: 10mm, LL: 5mmUL vs. LL production insufficiently investigated. LL focused on more due to easier accessibility to lower lids, especially w/ meibometry. Also, meibum from UL and LL mixed together during blinks so difficult to eval where it was produced.
Acini are constantly making new meibocytes, leading to constant production of meibum. Supported by increased amount of lipids in morning after sleep….less dryness in morning, seborrhea worse in mornings. Constant secretion increases pressure within an obstructed gland. Recovery time 2hrs…may be best to do WC and digital expressions at bedtime instead of mornings.
Bacterial lipases from commensal bacteria disrupt lipid formation, increasing melting point and leading to high viscosity lipid that mixes with desquamated epithelial cells, causing obstruction. Hormonal disturbances may also alter lipid production. Histology studies have shown lack of inflammatory leukocytes, chemokines and cytokines; indicating inflammation doesn’t represent a major etiologic factor in obstructive MGD, but rather part of a cascade of events to follow.
Normal tear meniscus: 0.34mm above lid margin w/ white lightOCT depth: 200 microns depth from personal experience
Low water content better for dry eyes. But high water content allows better continuity of lipid layer coverage.
Sources• The International Workshop on Meibomian Gland Dysfunction – Investigative Ophthalmology & Visual Science, March 2011 – >50 international experts, M.D.’s, O.D.’s, Ph.D’s; >2 year period• The Tear Film and Ocular Surface Society• The Ocular Surface• Ophthalmology Management• Optometric Management• Review of Optometry• Contact Lens Spectrum• Personal observations and experiences in clinical practice
MGD – Recommended DefinitionMeibomian 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.
Definition and Classification of MGD• MGD• Blepharitis: general term describing inflammation of the lid as a whole – Marginal Bepharitis: inflammation of the lid margin; includes both anterior and posterior blepharitis – Anterior Blepharitis: inflammation of lid margin anterior to gray line and centered around the lashes – Posterior Blepharitis: inflammation of posterior lid margin, of which MGD is only one cause (e.g. infectious, allergic)• Meibomian Gland Disease: used to describe a broader range of meibomian gland disorders, including neoplasia and congenital disease• Meibomitis/Meibomianitis: subset of MGD associated with inflammation of meibomian glands• Hypersecretory MGD/Seborrheic MGD: MGD with increased secretion of meibomian lipids• Hyposecretory MGD: decreased lipid secretion without obstruction of glands (result of CL wear?)• Obstructive MGD: decreased lipid secretion due to obstruction of meibomian glands. PROBABLY MOST COMMON FORM OF MGD.• COMD - Chronic Obstructive Meibomian Disease• NOMGD – Non-Obvious MGD: normal appearance of lids and gland orifices; found only by expression
PrevalenceThe International Workshop on Meibomian Gland Dysfunction:“MGD may well be the leading cause of dry eye disease throughout the world.”“…of the two currently accepted forms of dry eye, evaporative dry eye is thought to be significantly more common than aqueous- deficient dry eye.”• 3.5%-69.3% – Results vary widely depending on study populations (age, race) and lack of universal criteria for grading signs associated with MGD.
Tear Film Lipid Layer Function1. Provide a smooth optical surface for the cornea at the air-lipid interface2. Reduce evaporation of the tear film3. Enhance the stability of the tear film4. Enhance spreading of the tear film5. Prevent spillover of tears from the lid margin6. Prevent contamination of the tear film by microbial agents and organic matter7. Seal the apposing lid margins during sleep
Symptoms• Dryness • Eyelid redness• Redness • Eyelid itching• Watering/tearing • Crust on lids/lashes,• Burning/stinging especially in mornings• Eye irritation • Eyelids stuck together,• Itchy eyes especially in mornings• Gritty/sandy • Puffy eyelids• Sticky sensation • Sensitivity to light • Increased glare
Anatomy & Physiology• Arrangement – Parallel, length of tarsal plate, UL longer than LL• Number of glands – Depending on study, UL: 25-40 and LL: 20-30 – Total volume of UL glands approximately double that of LL glands – Central duct wider in lower lid – Insufficient studies to date as to which lid and where secretes most sebum (Nasal 1/3 or LL may be faulty given volume of UL glands)
Anatomy & Physiology• Pathway of meibum 1. Secretory acini filled with meibocytes create meibum 2. Short, lateral connecting ductule 3. Long, central duct 4. Excretory duct 5. Lipid reservoir 6. Tear film• Driving force of meibum delivery – Continuous secretion of meibum – Mechanical muscular action of blink• Recovery time after full expression: approx. 2 hours• Meibum melting point: 82-89F
Pathophysiology of MGDHyperkeratinization of excretory duct and orifice/ Altered lipid compensation → obstruction → increased intraglandular pressure → degenerative dilatation of ductal system → hyposecretion due to loss of meibocytes → gland atrophy → cell stress may ultimately trigger downstream occurrence of inflammation
Symptom Questionnaire• Does not distinguish between MGD and dry eye, or between aqueous deficient dry eye (ADDES) and evaporative dry eye (EDES)• Patients likely to develop over time elements of both ADDES and EDES• Not always high correlation of signs and symptoms• Source of symptoms from meibomian glands or from ocular surface?• MGD risk factor or cause of dry eye? Or dry eye risk factor or cause of MGD?• Timeline of events or severity before symptoms develop?
Eyelids• Telangiectasia • Anterior blepharitis• Overall lid margin • Tenderness to touch injection/hyperemia • Lid wiper epitheliopathy• Lid margin keratinization • Epithelial ridge• Eyelid thickening formation between• Dimpling/notching/pitting meibomian glands• Meibomian gland • Distichiasis concretions
Meibomian Glands Meibography/Meiboscopy!! Express!, Express!, Express!• Atrophy of terminal ducts • Number of functional glands• Absence of entire glands • Obstructive capping/plugging• Scarring of orifice • Expressibility• Obstructive capping/plugging • Color of meibum• Microchalazia/lipogranulomas • Consistency of meibum• Meibomian gland concretions
Tear Film ADDES vs. EDES vs. combination Quantity Quality• TBUT • TBUT pattern• Ocular Protective Index • Frothy tear film (OPI) and Blink Rate (BR) • Debris in tear film• Meniscus height/depth – Measured prior to NaFl dye • Osmolarity – OCT measurement of depth • Interferometry• Schirmer test • Evaluate in both white light• Phenol Red Test and with fluorescein• Osmolarity• Interferometry
Topical Rx Therapeutics• AzaSite, erythromycin – inhibit protein synthesis; Coverage and penetration of AzaSite >> erythromycin – immunomodulatory and anti-inflammatory effects; mechanism unclear• Besivance, et al fluoroquinilones – Minimal ocular surface toxicity; excellent coverage• Combo’s: Tobradex, Tobradex ST, Zylet• Restasis• FreshKote – Supplements all 3 layers; improves stability by increasing adhesion of molecules• metronidazole 1% ointment – Antibiotic for rosacea; mechanism unclear• Tea tree shampoo QD, 50% tea tree oil QW in presence of Demodex – No evidence yet that Demodex can cause MGD• Steroids?• NSAIDs??
Oral Rx Therapeutics• Tetracycline derivatives – Tetracycline 250mg QD-QID: anti-inflammatory, not anti- microbial – Doxycycline 50-100mg QD-BID: anti- inflammatory, potentially mildly anti-microbial – Minocycline 50-100mg QD-BID: Both anti-inflammatory and anti-microbial – Suppresses microbial lipase production, which is responsible for release of pro-inflammatory FFA’s and diglycerides – Usually well-tolerated; be knowledgeable of side effects• Erythromycin – Children and women
OTC Topical “therapeutics”• Systane Balance • Preservative-free?• Soothe XP • Best served cold?• Blink Tears • Gel, ointment ?• Refresh Optive• Systane Ultra• …and many others
Nutritional• Essential fatty acids: Omega-3,6,9 – Omega-3,9 vs. Omega-6 – Fish oil vs. flaxseed oil – No consensus on dosing yet• Hydration vs. dehydration• Spicy foods, and other triggers of rosacea• Fatty foods
Home Therapy & Maintenance• Warm compresses with lid massage/digital expression still gold standard• Forceful blinks with lid massage• Lid scrubs, saline-soaked cotton tip scrub• Hot/Cold goggles, face masks• Moisture Release Eyewear• Humidifiers
• Video of mastrota expression• Video of mastrota + MG expressor• Video of maskin probing
Contact Lens Considerations• Daily disposable lenses• Thin edge lenses• Low water content vs. High water content• No significant difference in evaporation between hydrogels vs. SiHy’s, but worse than non-wearers• Lipid deposits substantially higher in silicone hydrogels than conventional hydrogels – lotrafilcon A (Ciba) < galyfilcon A (Acuvue) < balafilcon A (B&L)• Hydrogen peroxide based solutions
Billing• Examination, 92002, 92012, 92004, 92014, E/M level codes:• External Photography, 92285: $27.64, bilateral• OCT of anterior segment, 92132: $36.05, bilateral• Tear Osmolarity, 83861: $24.01, unilateral, when CLIA Waiver categorization from FDA• Interferometry, 92136: $82.49, bilateral• Punctum Plug, 68761: $140.20, E1-E4• Evacuation of Meibomian Glands, 0207T: unilateral, Category III code• Advanced Beneficiary Notice of Noncoverage (ABN)• Informed Consent
My Recommendations from Experience• Mastrota Meibomian Paddle forceful • Maskin Intraductal Probing expressions – Pre-Op: – Pre-Op: • prior forceful expression preferred to • prior digital palpation preferred to understand which glands to target understand which glands to target • Insertion of BCL to protect cornea from • Insertion of BCL to protect cornea from anesthetics anesthetics • TetraVisc Forte ophthalmic gel • TetraVisc Forte ophthalmic gel • Compounded lidocaine 4% jelly in fornix • Compounded lidocaine 4% jelly in fornix and lid margin and lid margin • WC for 20 minutes • EMLA cream to dermal side of lids – Post-Op: • WC for 20 minutes • Irrigate eye and everted lids with – Post-Op: eyewash • Irrigate eye and everted lids with • Remove BCL eyewash • In-office antibiotic • Remove BCL • In-office NSAID • In-office antibiotic • Tobradex ST QID x2d • In-office NSAID • AzaSite qhs • Tobradex ST QID x2d • PF Blink/Optive/Systane • AzaSite qhs • RTC 1-2wks • PF Blink/Optive/Systane • RTC depends on diagnostic outcome of procedure
What’s in the Pipeline?• Tear Science LipiFlow Thermal Pulsation System – not approved in U.S. yet• Maskin Meibum Expressor, Rhein Medical, launches mid-July• Resolvyx RX-10045, topical resolvin• Remura (bromfenac for dry eye), ISTA Pharmaceuticals, Phase III• T-Pred (tobramycin 3%, prednisolone acetate 1%), ISTA Pharmaceuticals, likely enter Phase III in 2012• Can-Fite CF101, oral anti-inflammatory, Phase III for DES and psoriasis, ongoing studies for rheumatoid arthritis and glaucoma• Zylet ointment?? – come on Bausch&Lomb!!
Take Home Points Understand the differences in terminology; THEY ARE NOT SYNONYMOUS Distinguish the difference clinically between ADDES and EDES and treat specifically, not generically Develop a clinical evaluation routine. CEE’s may not be the same as targeted dry eye evaluations Consider the possible long-term effects of contact lens wear modalities Be the EXPERT for your patients. This is OUR specialty!