Dry eye diagnosis and treatments: The Elevator speeches COPE # Dry eye diagnosis and treatments: The Elevator speeches COPE # 5/11/2015.

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1 Dry eye diagnosis and treatments: The Elevator speeches COPE # Dry eye diagnosis and treatments: The Elevator speeches COPE # Milton M. Hom, OD, FAAO, FACAAI (Sc). eyemage@mminternet.com Disclosures Last 12 months: Allergan AMO Bausch/Valeant Alcon Cooper Shire 1

2 ω6 ω3 Do you prescribe omegas for dry eyes? A. Not at all B. Seldom C. Sometimes D. Frequently E. Always 6 clinical trials 2005 to clinical trials 2010 to 2015 Hom MM. Asbell PA. Barry B. Omegas and dry eye: more knowledge, more questions. in press. 2

3 790 participants in 7 independent studies Meta-analysis 5 studies ω3 TBUT significantly greater by 1.58 s Liu, Aihua, and Jian Ji. "Omega-3 Essential Fatty Acids Therapy for Dry Eye Syndrome: A Meta-Analysis of Randomized Controlled Studies." Medical science monitor: international medical journal of experimental and clinical research 20 (2014): ω3 Significantly improve the Schirmer s test Did not significantly improve the OSDI test results Liu, Aihua, and Jian Ji. "Omega-3 Essential Fatty Acids Therapy for Dry Eye Syndrome: A Meta-Analysis of Randomized Controlled Studies." Medical science monitor: international medical journal of experimental and clinical research 20 (2014): Fatty acid designation 6 3 Dietary sources Dietary intake (dietary energy) Sunflower oil, safflower oil, corn oil, soy oil Large dietary intake (7 8% dietary energy) Flaxseed oil, walnut oil, canola oil, fish oil Small dietary intake ( % dietary energy) Metabolism 6 fatty acid metabolism Linoleic acid 3 fatty acid metabolism Linoleic acid Gamma linoleic acid (GLA) Steridonic acid Dihomo gamma linoleic acid (DGLA) Eicosatetraenoic acid (EPA) PGE1 Docosahexaenoic acid (DHA) Arachadonic acid Anti inflammatory & thromolyticinducing Eicosanoids (Caution: bleeding disorders) Inflammation & platelet aggregation inducing Eicosanoids (Caution: thrombosis, coronary heart problems) 3

Eicosanoids Omega-6 Increase blood pressure Inflammatory Platelet aggregation Thrombosis Vasospasm Allergic reactions Cell proliferation Eicosanoids Omega-3 Increase

4 Eicosanoids Omega-6 Increase blood pressure Inflammatory Platelet aggregation Thrombosis Vasospasm Allergic reactions Cell proliferation Eicosanoids Omega-3 Increase blood pressure-opposite Inflammatory-opposite Platelet aggregation-opposite Thrombosis-opposite Vasospasm-opposite Allergic reactions-opposite Cell proliferation-opposite 4

The ideal ω6:ω3 ratio in the diet is approximately 4:1 Current Western diets that ratio is closer to 15:1 Simopoulos AP. (2002) "The importance of the ratio of omega- 6/omega-3 essential fatty acids.

Greater bleeding with ω3 Not recommended for surgery This case reveals a significant rise in INR after the dose of concomitant fish oil was doubled Buckley, Mitchell S., Angela D. Goff, and Walter E.

5 The ideal ω6:ω3 ratio in the diet is approximately 4:1 Current Western diets that ratio is closer to 15:1 Simopoulos AP. (2002) "The importance of the ratio of omega- 6/omega-3 essential fatty acids." Biomed Pharmacother, 56(8): Greater bleeding with ω3 Not recommended for surgery This case reveals a significant rise in INR after the dose of concomitant fish oil was doubled Buckley, Mitchell S., Angela D. Goff, and Walter E. Knapp. "Fish oil interaction with warfarin." Annals of Pharmacotherapy 38.1 (2004): DHA-Lovaza-platelet-inhibition-bleeding-risk-mechanism High blood concentrations ω3 Linked to increase prostate cancer risk Brasky TM, Darke AK, Song X, et al. Plasma phospholipid fatty acids and prostate cancer risk in the SELECT Trial. J Natl Cancer Inst 2013;105:

6 Hydro-Eye Hydrate Essential TheraTears Nutrition BioTears Dry Eye Formula EyePromise EZ Tears PRN Nordic Naturals Anshel J. A nutritional approach to treating dry eyes. Texas Optometric Association Supplement ω6 ω3 Dose PRN Dry eye Omega ω3 EPA 4 gels/day Dry Eye Formula ω3 EPA/DHA 3 gels/day TheraTears Nutrition Hydro-Eye BioTears EyePromise EZ Tears Nordic Naturals Complete Omegas ω3 EPA/DHA/ALA Flaxseed oil ω6 GLA ω3 EPA/DHA ω6 GLA ω3 EPA/DHA ω6 GLA ω3 EPA/DHA ω6 GLA ω3 EPA/DHA 3 gels 4 gels 4 gels/day 2 gels 2 gels Supplement ω6 ω3 MSRP Per gel/cap PRN Dry eye Omega ω3 120 $ Dry Eye Formula ω3 90 $ TheraTears Nutrition ω3 Flaxseed 90 $ Hydro-Eye ω6 ω3 120 $ BioTears ω6 ω3 120 $ EyePromise EZ Tears ω6 ω3 60 $ Nordic Naturals Complete Omegas ω6 ω3 120 $

7 DREAM study Dry eye assessment and management study (DREAM) First NIH sponsored dry eye study Multi-site 579 patients 2 years ω3 2000mg EPA, 1000mg DHA/day Placebo 7

"the direction of response of a body function to any agent depends to a large degree on the initial level of that function Wilder's law of initial value Buckley, Mitchell S., Angela D.

com/articles/fish-oil-omega-3-fatty-acids-epa- DHA-Lovaza-platelet-inhibition-bleeding-risk-mechanism Meat cuts 18 cattle Grain vs grass fed Trimmed of visible fat & connective tissue and then minced

8 "the direction of response of a body function to any agent depends to a large degree on the initial level of that function Wilder's law of initial value Buckley, Mitchell S., Angela D. Goff, and Walter E. Knapp. "Fish oil interaction with warfarin." Annals of Pharmacotherapy 38.1 (2004): DHA-Lovaza-platelet-inhibition-bleeding-risk-mechanism Meat cuts 18 cattle Grain vs grass fed Trimmed of visible fat & connective tissue and then minced 7 g were used for fatty acid (FA) analysis. Ponnampalam, Eric, Neil Mann, and Andrew Sinclair. "Effect of feeding systems on omega- 3 fatty acids, conjugated linoleic acid and trans fatty acids in Australian beef cuts: potential impact on humnan health." Asia Pacific Journal of Clinical Nutrition 15.1 (2006): significantly higher level of total omega- 3 (ω-3) in grass-fed beef (P< ) than the grain-fed groups regardless of cut types. Ponnampalam, Eric, Neil Mann, and Andrew Sinclair. "Effect of feeding systems on omega- 3 fatty acids, conjugated linoleic acid and trans fatty acids in Australian beef cuts: potential impact on humnan health." Asia Pacific Journal of Clinical Nutrition 15.1 (2006):

When cattle are taken off grass and shipped to a feedlot to be fattened on grain, they lose their valuable store of LNA as well as two other types of omega-3 fatty acids, EPA and DHA. http://www.

9 When cattle are taken off grass and shipped to a feedlot to be fattened on grain, they lose their valuable store of LNA as well as two other types of omega-3 fatty acids, EPA and DHA. Duckett, S. K., D. G. Wagner, et al. (1993). "Effects of time on feed on beef nutrient composition." J Anim Sci 71(8): Each day that an animal spends in the feedlot, its supply of omega-3s is diminished Duckett, S. K., D. G. Wagner, et al. (1993). "Effects of time on feed on beef nutrient composition." J Anim Sci 71(8):

10 What percentage of your patients have blepharitis? A. Less than 10% B. 10% to 25% C. 25% to 35% D. 35% to 50% E. Over 50% Demodex Demodex Ectoparasites-most common in man 100% in patients 70 years old plus Mite density rises in the sixth decade of life Level until the eighth decade of life. 10

11 1. Clinical history: blepharitis, dry eyes or ocular allergy 2. Slit-lamp examination: cylindrical dandruff 3.Microscopic confirmation: counting of Demodex eggs, lavae and adults. Hom MM, Mastrota KM, Schachter SE. Demodex. Optom Vis Sci Jul;90(7):e Clinical history Symptoms: Itch, burning, foreign body sensation, crusting, redness, blurry vision Hom MM, Mastrota KM, Schachter SE. Demodex. Optom Vis Sci Jul;90(7):e

12 Demodex mite infestation 85% also have MGD de Venecia AB. Siong RLB. Demodex sp. infestation in anterior blepharitis, meibomian gland dysfunction and mixed blepharitis. Phillipine Journal of Ophthalmology. 2011;36(1): Blepharitis & demodex Meta-analysis of 11 studies Statistically significant association Zhao YE,Wu LP,Hu L,Xu JR. Association of blepharitis with Demodex: a meta-analysis. Ophthalmic Epidemiol 2012;19:95Y102. Lid Debris Grade 4 (Very Severe) 50 year-old 3 clumps/strands >40 collarettes 12

13 2. Slit lamp evaluation 12.9 mites per patient with cylindrical dandruff (CD) 0.35 mites without CD 30 times higher when cylindrical dandruff is present. 1. Gao YY. Di Pascuale MA. Li W. et.al. High Prevalence of Demodex in Eyelashes with Cylindrical Dandruff. Invest. Ophthalmol. Vis. Sci. 2005;46(9): Cylindrical dandruff was pathognomonic for the presence of demodex infestation. 1. Gao YY. Di Pascuale MA. Li W. et.al. High Prevalence of Demodex in Eyelashes with Cylindrical Dandruff. Invest. Ophthalmol. Vis. Sci. 2005;46(9):

Alejo RL, Valenton MJ, Abendanio R. Demodex folliculorum infestation of the lids in Filipinos. Philipp J Ophthalmol 1972;4:110Y3.

14 Blepharitis with demodex 62.9% Sumer et. al. 88% Alejo et.al. 97% De Venecia and Siong Sumer Z, Arıcı MK,Topalkara A,Ozçelik S, Yıldırım S.[Incidence of Demodex folliculorum in chronic blepharitis patients]. Cumhuriyet Univ Tıp Fak Dergisi 2000;22:69Y72. Alejo RL, Valenton MJ, Abendanio R. Demodex folliculorum infestation of the lids in Filipinos. Philipp J Ophthalmol 1972;4:110Y3. De Venecia AB, Siong RL. Demodes sp. infestation in anterior blepharitis, meibomian gland dysfunction, and mixed blepharitis. Philipp J Ophthalmol 2011;36:15Y22. 14

15 Distention caused by waste products Half of mites are follicle opening are dead Demodex have no anus, and stores its waste in large cells within its gut. When the mite dies, its body disintegrates and an explosion of waste can be released. 3. Epilate and microscope 15

16 Celestron LCD Digital Microscope II (Black) Celestron 5 MP LCD Deluxe Amazon $200 approx Have not tried 16

17 What percentage of your patients have rocasea? A. Less than 10% B. 10% to 25% C. 25% to 35% D. 35% to 50% E. Over 50% 17

Rosacea and demodex Meta-analysis of 48 studies 10 different countries 28,527 subjects Rosacea patients 7-8x chance have Demodex Zhao YE, Wu LP, Peng Y, Cheng H.

18 Rosacea and demodex Meta-analysis of 48 studies 10 different countries 28,527 subjects Rosacea patients 7-8x chance have Demodex Zhao YE, Wu LP, Peng Y, Cheng H. Retrospective analysis of the association between Demodex infestation and rosacea. Arch Dermatol 2010;146:896Y902. Demodex is highly photophobic and avoids light hundreds of mites appear in severely infested lids but has never seen a mite emerge completely. Coston Coston TO. Demodex folliculorum blepharitis. Trans Am Ophthalmol Soc. 1967;65:

19 Tea Tree oil Ocusoft Cliradex Australian generic brand (Target) Oust Ocusoft Blephadex Macular Health 19

20 1. Clean lids with lid scrub (Ocusoft, etc) 2. Instill proparacaine/tetravisc/nsaid as drop in eyes and along lid margins with cotton swab. 3. Apply TTO (Ocusoft or mix) with cotton swab along lid margins. Use a fresh swab for each lid margin. Modified from Cliff Silverman, OD 4. Clean lashes with the short Bleph brush (Ocusoft demodex kit) removing all collarettes and debris that remain. Optional: cotton swab 5. After 5 or more minutes, irrigate. I prefer CL solution with PHMB ( acaricide ) 6. Clean again with lid cleaning pads. 7. Repeat TTO, irrigate and scrub again 8. Send home with Cliradex 2x day if moderate/severe, 1x day if mild/moderate 9. Return in about 2 weeks for 2nd treatment 20

21 Tip sheet If you see rosacea and see no demodex, you are missing it Everyone has it, normal mites; like bacteria Q: infestation or not In-office will not get rid all of them We only try to control the numbers Add Tea tree oil shampoo Add Tea tree oil soaps Tip sheet Space 1-2 weeks apart, lifecycle of the mite Minimum 2 treatments, sometimes more is needed Use Cliradex pads 2 x day or 1x day evenings Squeeze pads before opening to spread TTO, sometimes pads are dry Use pads on eyebrows and rest of face Tip sheet Squeeze and fan Lay pads on lids without scrubbing for most sensitive patients Q: Do your own mix or not? Use at own risk TTO:Macadamian nut oil; 50:50 mix Be careful of too much TTO with Bleph brush Caraway oil can be used, but $$ Emulsion drops with oil activates the mites 21

22 Tip sheet Mites in children - Poster Friday Scott Schachter Mites mistaken for allergy Look for lots of cuff dandruff to epilate. Look for distended bases. Waste products & dead mites. Go for juicy or sick lashes (short, discolored, mis-directed, etc) Tip sheet Drop cover slip first, then add emulsion drop at the side Show and tell Give patients cell phone number 82 female patients with perioral dermatitis 70 control female subjects. Mite density increased significantly with length of treatment with topical steroids (p<0.001) Dolenc-Voljc M, Pohar M, Lunder T. Density of Demodex folliculorum in perioral dermatitis. Acta Derm Venereol. 2005;85(3):

23 Strong link to rosacea Strong link to MGD (85%) Under-diagnosis = increasing mite counts? Zhao YE. Wu LP. Peng Y. et.al. Retrospective analysis of the association between Demodex infestation and rosacea. Arch Dermatol Aug;146(8): De Venecia AB. Siong RLB. Demodes sp. infestation in anterior blepharitis, meibomian gland dysfunction, and mixed blepharitis. Phillipp J Ophthalmol 2011;36(1):15-22 Kheirkhah A, Casas V, Li W, Raju VK, Tseng SC. Corneal manifestations of ocular Demodex infestation. Am J Ophthalmol. 2007;143(5): Steroids 2. Emulsion drops 3. Restasis 4. Prostaglandins 5. Latisse 6. Antibiotics (waste of time) e-cigarettes 23

24 How many vape/e-cig shops/kiosks are in your area? A. None B. 1 C. 2 D. 3-5 E. More than 5 Battery operated Vaporizes nicotine Projected to surpass cigarettes in 10 years Foggs MB. ACAAI News. American College of Allergy, Asthma and Immunology

25 Dyethylene glycol-antifreeze toxin Cartridges leak-toxic exposure nicotine Smoking five minutes-pulmonary function effects Foggs MB. ACAAI News. American College of Allergy, Asthma and Immunology Available to minors online and shopping malls in some states Flavors to appeal Foggs MB. ACAAI News. American College of Allergy, Asthma and Immunology E-cigarette are typically solutions of propylene glycol, glycerol, or both, plus nicotine and flavorant chemicals. Jensen RP. Luo W. Pankow JF. et.al. Hidden Formaldehyde in E-Cigarette Aerosols N Engl J Med 2015; 372:

26 Formaldehyde is a known degradation product of propylene glycol that reacts with propylene glycol and glycerol during vaporization Jensen RP. Luo W. Pankow JF. et.al. Hidden Formaldehyde in E-Cigarette Aerosols N Engl J Med 2015; 372: inhaling gaseous formaldehyde longterm vaping is associated with an incremental lifetime cancer risk of Jensen RP. Luo W. Pankow JF. et.al. Hidden Formaldehyde in E-Cigarette Aerosols N Engl J Med 2015; 372: risk is 5 times as high or even 15 times as high as the risk associated with longterm smoking. Jensen RP. Luo W. Pankow JF. et.al. Hidden Formaldehyde in E-Cigarette Aerosols N Engl J Med 2015; 372:

27 What percentage of your patients have allergy? A. Less than 10% B. 10% to 25% C. 25% to 35% D. 35% to 50% E. Over 50% Hom MM. Nguyen AL. Bielory L. Allergic conjunctivitis and dry eyes. Annals of Allergy, Asthma & Immunology. Volume 108, Issue 3, Pages , March

King Edward I Banned coal burning England, 1306 Death

com/offbeatnews/environmentalism-in-1306/725 http://www.

com/offbeatnews/environmentalism-in-1306/725 Fel d-i

28 King Edward I Banned coal burning England, 1306 Death penalty or torture Fel d-i glycoprotein: Secreted by sebaceous glands Found in fur, urine, saliva Can remain airborne for months 10x smaller than pollen 28

29 Approximately 17% are allergic to cats One third ignore medical advice Males castrated much lower (5.46 to 1.28) Washing/baths only effective for 3 hours HEPA vacuum + HEPA room filtration works, each alone has diminished effect Plug-ins have 20 Volatile organic compounds (VOC) 1/3 classified as toxic or hazardous Scented candles produce: Soot, lead, organic compounds and VOCs. 29

PataDay HD olopatadine (0.77%) Legacy versions PataDay (0.2%); Patanol (0.1%) Ocular itch significantly reduced at 24- hours McLaurin, Eugene, Narvekar, Abhijit, Gomes, Paul J.

30 PataDay HD olopatadine (0.77%) Legacy versions PataDay (0.2%); Patanol (0.1%) Ocular itch significantly reduced at 24- hours McLaurin, Eugene, Narvekar, Abhijit, Gomes, Paul J. Phase 3 Study of Efficacy and Safety of Once-daily Olopatadine Hydrochloride, 0.77% Ophthalmic Formulation in Patients With Allergic Conjunctivitis Using the Ora Conjunctival Allergen Challenge Model (Ora-CAC *) ARVO 2014 Hom, MM. O Dell LE. May CJ. Bielory L. (2015). Ocular Papillary Changes on the Caruncle Surface in Allergic Conjunctivitis. Journal of Allergy and Clinical Immunology, 134(2) 30

285 consecutive patients were seen in two clinics. Caruncle scores were consistently higher (mean 1.76 SD 0.82) than palpebral conjunctiva scores (mean 1.34 SD 0.74).

31 285 consecutive patients were seen in two clinics. Caruncle scores were consistently higher (mean 1.76 SD 0.82) than palpebral conjunctiva scores (mean 1.34 SD 0.74). Significant differences were found between the caruncle and palpebral surfaces scores (p<.0001) Pearson correlation was 0.3 (p<.0001) Hom, MM. O Dell LE. May CJ. Bielory L. (2015). Ocular Papillary Changes on the Caruncle Surface in Allergic Conjunctivitis. Journal of Allergy and Clinical Immunology, 134(2) Papillary changes in the lids are the hallmark of allergic conjunctivitis signs Can also occur in caruncle (mild correlation) Caruncle surface changes are more severe than lid surface changes. May be due to greater inflammatory response in caruncle than rest of the eye May explain why allergic eye rubbing more likely to occur in the corner of the eyes (caruncle area) Along with the location of eye rubbing, this can help to diagnose allergic conjunctivitis. Hom, MM. O Dell LE. May CJ. Bielory L. (2015). Ocular Papillary Changes on the Caruncle Surface in Allergic Conjunctivitis. Journal of Allergy and Clinical Immunology, 134(2) 31

32 White Mulberry White Mulberry 32

33 Sycamore Sycamore Ash/Washington springbeauty 33

..despite some floristic differences between the two areas Ortu E, Klotz S, Brugiapaglia E, et.al.

34 Ash/Washington springbeauty Tree ATL January to June strong relationship exists between altitude and variations in pollen...despite some floristic differences between the two areas Ortu E, Klotz S, Brugiapaglia E, et.al. Elevation-induced variations of pollen assemblages in the North-western Alps: An analysis of their value as temperature indicators. C R Biol Nov-Dec;333(11-12): Epub 2010 Nov 5. 34

35 $ tablets Thank you! Milton M. Hom, OD, FAAO. 35

COPE#37748-AS. Demodex. Scott Schachter Scott Hauswirth Katherine Mastrota Mario Gutierrez Ben Gaddie Christine Sindt Scheffer Tseng.

COPE#37748-AS. Demodex. Scott Schachter Scott Hauswirth Katherine Mastrota Mario Gutierrez Ben Gaddie Christine Sindt Scheffer Tseng. Disclosures Mites that eat and live on your lids Mites that eat and live on your lids COPE#37748-AS COPE#37748-AS Last 12 months: Allergan AMO Bausch/Valeant NiCox Cooper Milton M. Hom, OD, FAAO, FACAAI(Sc).