Dry Eye update

1. Dry Eye update Coordinating teaching, diagnosis and therapy Robert Fintelmann M.D., FACS, Kevin Helmuth O.D.

2. Robert Fintelmann, M.D., FACS Dr. Robert Fintelmann completed his doctorate at the University of Ulm in Germany, an ophthalmology residency at Wills Eye Institute in Philadelphia, PA, and a Corneal and Refractive Surgery Fellowship at the University of California, San Francisco. Dr. Fintelmann has performed thousands of cataract surgeries, over 2,000 vision correction procedures (LASIK, PRK, and ICL), &hundreds of corneal transplants. His experience includes: laser-assisted cataract surgery, full corneal transplants, partial thickness corneal transplants (DSAEK, DMEK, DALK), along with minimally invasive transplants of either the anterior or posterior portions of the cornea. In clinic, he enjoys treating ocular surface disease (dry eye), and helping patients achieve relief from their chronic eye irritation. Dr. Fintelmann is a board-certified Diplomate of the American Board of Ophthalmology and serves as an examiner for the oral board exams. He is a fellow of the American College of Surgeons and a member of multiple professional organizations, and he performs research &publishes articles in peer-reviewed journals.

3. Kevin Helmuth O.D. Dr. Kevin Helmuth, received his doctorate from the Pacific University College of Optometry. He currently serves as the Director of Clinic Operations at the AZ College of Optometry where he also works as an Associate Professor. Prior to coming to Midwestern University, Dr. Helmuth spent nearly 12 years working in Native American health facilities. He previously served as the Director of Optometry for the Gila River Indian Community, Hu Hu Kam Memorial Hospital in Sacaton, Arizona; and the Chief of Optometry for the Creek Nation in Okemah, Oklahoma. He has a clinical and research interest in Dry Eye.

4. Financial Disclosures Neither Dr. Fintelmann nor Dr. Helmuth have any financial disclosures to report. <a href='https://newvitruvian.com/image/pocket-clipart-poverty/1092570.html'>Image credit</a>

5. Objectives Discuss new dry eye therapies that will be coming to the marketplace soon Re-visit Meibomian Gland Dysfunction and therapies to address it Review the special challenges that are unique to treating dry eye Discuss the importance of developing a standardized method of evaluating dry eye patients Review some effective tools that assist in patient communication Examine a method for not losing site of the big picture in this complicated condition Understand the importance of incorporating a multi-disciplinary approach

6. New Therapies Medications New Technology CEQUA (cyclosporin A 0.09%) Highest concentration of Cyclosporin A Uses a novel nanomiceller technology which allows it to penetrate the tear layer better Purportedly shows quicker results than either Restasis or Xiidra in corneal staining and tear production KLARITY-C (cyclosporine/chondroitin sulfate 0.1% ophthalmic emulsion, Imprimis Pharmaceuticals) Compounded, preservative-free, BID Xiidra (lifitegrast 5%) Multiple Other Meds in Clinical Trials: KPI-121 (0.25% loteprednol etabonate ophthalmic suspension, Kala Pharmaceuticals)  Thymosin β-4.RGN-259 TearCare Automated heat device applied to the lids $5500 after rebate $250/procedure renewable costs 12-15 minute tx followed by manual expression

7. Therapy Update Medications New Technology VITAL TEARS (Autologous Serum) Ordered as a single 2–3 month supply or as an on-going subscription. Provided in 3 ml aliquots. The drops last 1 week in refrigeration and 6 months frozen COSMESIS DISCUSSION Digital Heat Inc.

8. Re-visiting MGD treatment Lipiflow and ILux Lipiflow is well established Studies and experience shows improvement of signs and symptoms when glands are present Promoting it as a silver bullet which would make money hurt its implementation Cost is a barrier (definition of success crucial) Results take time Does not fix all of the problems

9. MGD treatment Lipiflow and ILux Price created incentive for competition Ilux has the same goal Works in smaller fissures Smaller device Disposable first cheaper now more expensive than lipiflow

10. MGD treatment Intense Pulsed Light (IPL) Used for years in dermatology Suggested use in dry eye to address inflammation Exact mechanism of action unknown Best results in patients with rosacea Treatment parameters vary With/without expression Midface versus full face Different machines With/without probing?

11. MGD treatment IPL Broad spectrum light source xenon bulbs 500-1200nm wavelength FDA approval 1995 Taken up by pigment (melanin, hemoglobin, artificial pigment e.g. eyeliner tattoo) Different filters and pulses Good safety profile when used as intended

12. MGD treatment IPL Complementary to lipiflow Works in inflammatory conditions Improvement in more advanced cases No renewables/Price point Several treatments necessary Improvement noted earlier # of treatments done at MWU

13. Probing of the Meibomian Glands Multiple probes are available 1mm, 2mm, 2.5mm, 4mm or 6mm. Start with 2mm. For clogged meibomian glands, particularly those inducing a feeling of pressure/discomfort. Takes 5-30 minutes Use lidocaine on the lid margin Provides both immediate and long-term effects on symptoms and signs Longevity of effect variable, retreat in 6-18 month time frame or possibly beyond. Price considerations Maskin Meibomian Gland Intraductal Probe

14. The Difficulty of Treating Dry Eye Glaucoma Treatments Prostaglandin analogs Beta Blockers Carbonic anhydrase inhibitors Alpha Agonists Rho khinase inhibitors Combination Drugs LPI ALT/SLT Trabeculectomy MIGS

15. The Difficulty of Treating Dry Eye Cyclosporin A variants Xiidra Warm compresses/Heat mask Moisture goggles Artificial tears (preserved) Artificial tears (non-preserved) Gels Ointments Sleep shields Nutraceuticals Intense Pulsed Light (IPL) Lipiflow iLux TearCare Aqueous secretagogues Mucin secretagogues Intraductal Gland Probing Lid debridement Manual gland expression Topical NSAIDS Tetracyclines Macrolides Topical antibiotics Tarsorrhaphy Conjunctivochalasis repair Environmental considerations Blinking exercises Increased fluid intake Dry Eye Treatments

16. The Difficulty of Treating Dry Eye Addressing other pathology is crucial Conjunctivochalasis variable in presentation and contribution to symptoms Can be addressed in clinic with cautery Improving surface prior to intervention results in smoother recovery EBMD, radial keratotomy, pterygium and scars Affect test results May need to be addressed surgically to get desired outcome Lid position Can be underlying pathology Work with surgeon who understands dry eye Limbal stem cell deficiency Mistaken for dry eye

17. InTEGRATING new treatments Both short and long-term views are important

18. Standardizing approach Consistency improves care and learning

19. Standardization Evaluation The Diagnosis of Dry Eye is mostly based on symptoms Our template standardizes approach to the patient, teaching, treatment and outcome evaluation. standardized grading scales e.g. staining, meibomian gland expression, redness scales, NIKTBUT, lissamine green, fluorescein etc. Immediate availability of these scales e.g. pictures within the E.H.R. that provide grading assistance for doctors and students alike. better teaching environment by synchronizing exam protocol and messaging to students/patients. Improved assessment of therapy success since both signs and or symptoms can improve

20. Standardization Use of technology Meibography NIKTBUT Tear film analysis Ocular surface analysis Provides communication tools to convey diagnosis and problems to patients Provides visualization of findings to students and doctors Underlines multifactorial and interconnected nature of Dry Eyes and its effects on vision and surgical outcomes

21. Standardization Treatment Treatment tables Standardize treatment, facilitate decision making Graphical analysis over time Emphasize treatment effect, enhance compliance Chronological record of treatment What has been done? What worked? Easier to integrate new treatment options while keeping established options on everybody’s mind. Provides framework for better and more impactful research opportunities.

22. Standardizing your Evaluations Case history Personal ocular/medical History OSDI / SPEED questionnaire Oculus 5M Meibography (dropout/truncation) NIKTBUT Tear meniscus Conjunctival Injection Tears Zone Quick and/or Schirmers Fl-TBUT Cornea/Conjunctiva Corneal staining (Fluorescein/Lissamine) Conjunctival staining (Fluorescein/Lissamine) Conjunctivochalasis Corneal/Conjunctival filaments Other corneal pathology Lids Floppy eyelids Blepharitis (Cylindrical?) Lid position Lid retraction Lagophthalmos Blink type Blink rate Meibomian gland expression Meibum quality Line of Marx Telangiectasia Other Dry Mouth Rosacea Contact lenses Systemic meds score Compliance rating For Dry Eye Work-Ups

23. Standardizing your Evaluations Case history Personal ocular/medical History OSDI / SPEED questionnaire Tears Fl-TBUT Cornea/Conjunctiva Corneal staining (Fluorescein/Lissamine) Conjunctival staining (Fluorescein/Lissamine) Lids Blepharitis (Cylindrical?) Meibomian gland expression Meibum quality Other Systemic meds score Compliance rating For Dry Eye Follow-Ups

24. Exam

25. Technology

26. Managing the Chronic Patient The value of graphical analysis

27. Systemic Medication Score Estrogen Progesterone Loratadine (Claritin) Chlorpheniramine (Chlor-Trimetan) Diphenhydramine (Benadryl) Furosemide (Lasix) Hydrochlorothiazide Isoretinoin IsoTretinoin Cyclophosphamide (Cytoxan) Cetirizine (Zyrtec) Desloratadine (Clarinex) Sertraline (Zoloft) Paroxetine (Paxil) Amitriptyline (Elavil/Endep) Doxepin (Adapin/Sinequan) Ibuprofen Propoxyphene Napsylate + Acetomeniphen (Darvocet-N) Hydrocodone (Lortab) Lansoprazole (Prevacid) Esomeprazole (Nexium) Omeprazole (Prilosec) Ranitidine (Zantac) Cidetidine (Tagamet) Thioridazine (Mellaril) Chlorpromazine (Thorazine) Dry Eye Inducing Systemic Drugs

28. Managing the Chronic Patient The value of graphical analysis

29. Managing the Chronic Patient Not losing the forest for the trees The importance of a treatment table

30. Managing the Chronic Patient The personalized treatment plan Building Compliance Through Improved Patient Communication

31. Interdisciplinary approach Rheumatology Psychology Dry Eye patients suffer from greater depression, anxiety and one case reported higher suicidal ideation Dry Eye patients have shown reduced quality of life in multiple studies Two Depression Screening Questions to ask your patients. 1) During the past 2 weeks, have you often been bothered by feeling down, depressed, or hopeless? 2) During the past 2 weeks, have you often been bothered by little interest or pleasure in doing things?

32. References J Vis Exp. 2019 Apr 1;(146). doi: 10.3791/57811 Toyos R, et al. Photomed Laser Surg. 2015;(33)1:41-46 Clin Ophthalmol. 2019 Jan 22;13:189-198. doi: 10.2147/OPTH.S191588. eCollection 2019 Graefes Arch Clin Exp Ophthalmol. 2019 Mar;257(3):591-599. doi: 10.1007/s00417-019-04241-1. Epub 2019 Jan 15. Cornea. 2019 Mar;38(3):311-317. doi: 10.1097/ICO.0000000000001854 Eye Contact Lens. 2018 Nov;44 Suppl 2:S404-S409. doi: 10.1097/ICL.0000000000000550 The British Journal of Dermatology. 2018;179(2):282-289 BMC Psychiatry. 2018 May 16;18(1):131. doi: 10.1186/s12888-018-1715-x Brain Behav. 2016 Oct 13;6(12):e00586. doi: 10.1002/brb3.586. eCollection 2016 Dec. Sci Rep. 2016 Mar 1;6:22480. doi: 10.1038/srep22480. Curr Eye Res. 2016 Aug;41(8):1044-1049. Epub 2015 Dec 7. Curr Eye Res. 2016 May;41(5):590-9. doi: 10.3109/02713683.2015.1056804. Epub 2015 Sep 4 Canadian Agency for Drugs and Technologies in Health; 2018 Feb 8 www.webmd.com/skin-problems-and-treatments/news/20120830/are-mites-causing-your-rosacea#1 Joint Bone Spine, 2016 Dec;83(6):681-685. doi: 10.1016/j.jbspin.2015.10.005. Epub 2016 Jan 13 Mickles,Chandra OD, MS, Review of Optometry, Dry Eye Drugs: New Approaches to an Old Problem, March 15, 2019 Maskin SL. Intraductal meibomian gland probing relieves symptoms of obstructive meibomian gland dysfunction. Cornea 2010;29(10):1145–1152. Fermon S, Hindi Zaga I, Alvarez Melloni D. Intraductal meibomian gland probing for the treatment of blepharitis. Arch Soc Esp Oftalmol 2015;90(2):76–80. Nakayama N, Kawashima M, Kaido M, Arita R, Tsubota K. Analysis of Meibum Before and After Intraductal Meibomian Gland Probing in Eyes With Obstructive Meibomian Gland Dysfunction. Cornea 2015;34(10):1206–1208. https://dryeyeandmgd.com/dry-eye-and-mgd-treatments/lipiflow-treatment-leading-cause-dry-eye/ http://www.eyelidsurgery.co.uk/ectropionentropion-surgery/ https://www.atlasophthalmology.net/photo.jsf;jsessionid=0AC5E47D464510B839F301A57DA39A59?node=625&locale=pt https://psychologybenefits.org/2015/01/29/4-tips-for-preventing-and-coping-with-hiv-related-short-term-memory-loss/ http://shine365.marshfieldclinic.org/wellness/feeling-anxious-worried-or-panicky/ https://www.dawn.com/news/1454338 https://www.seebetterflorida.com/lumenis-optima-ipl/