Lecture 2 OcSurface Pharm.pdf

Ocular Surface Diesease Treatment Options Pharmacology II Ocular Surface Disease Treatment Options Diane T. Adamczyk, OD,FAAO Pharmacology II 1 Diane T. Adamczyk, OD, FAAO Copyright © 2024 1 1 Ocular Surface Diesease Treatment Options Pharmacology II Dry Eye TFOS DEWS II (Tear Film and Ocu...

Ocular Surface Diesease Treatment Options Pharmacology II Ocular Surface Disease Treatment Options Diane T. Adamczyk, OD,FAAO Pharmacology II 1 Diane T. Adamczyk, OD, FAAO Copyright © 2024 1 1 Ocular Surface Diesease Treatment Options Pharmacology II Dry Eye TFOS DEWS II (Tear Film and Ocular Surface Dry Eye WorkShop II) global dry eye definition: “Dry eye is a multifactorial disease of the ocular surface characterized by a loss of homeostasis of the tear film, and accompanied by ocular symptoms, in which E Ø tear film instability and hyperosmolarity, t i o Ø ocular surface inflammation and damage, and l Ø neurosensory abnormalities play etiological roles.” o g y The Ocular Surface 15 (2017) 276e283 (TFOS DEWS II Definition and Classification Report 2 Diane T. Adamczyk, OD, FAAO Copyright © 2024 2 -balance between the tears and the cornea is not happening -starts to suck fluid from the cornea epithelial cells causing an inflammatory process -all three play a role in etiology of dry eye 2 Ocular Surface Diesease Treatment Options Pharmacology II The Vicious Circle of Dry Eye Disease (hyperosmolarity) The core mechanism of DED is tear hyperosmolarity. >>>It damages the ocular surface both directly and by initiating inflammation. The Ocular Surface 15 (2017) 438e510 (Pathophysiology Report) 3 Diane T. Adamczyk, OD, FAAO Copyright © 2024 3 -want to know how to treat hyperosmolarity and inflammation 3 Ocular Surface Diesease Treatment Options Pharmacology II The Vicious Circle of Dry Eye Disease (hyperosmolarity) In DED, tear hyperosmolarity: • Sets up a cascade of signaling events within surface epithelial cells • This leads to the release of inflammatory mediators and proteases. • Mediators and tear hyperosmolarity cause: • goblet cell and epithelial cell loss and • damage to the epithelial glycocalyx Damage is reinforced by inflammatory mediators from activated T-cells, recruited to the ocular surface. The net result is: • Punctate epitheliopathy and tear film instability >>> leads to tear film break-up. • This break-up exacerbates and amplifies tear hyperosmolarity>>> completes the Vicious Circle of events >>>> leads to ocular surface damage. The Ocular Surface 15 (2017) 438e510 (Pathophysiology Report) 4 Diane T. Adamczyk, OD, FAAO Copyright © 2024 4 There is a cycle that occurs which comes first the inflammation or hyperosmolarirty or vice versa or both at the same time and it depends - 4 Ocular Surface Diesease Treatment Options Pharmacology II The Vicious Circle of Dry Eye Disease (DED Forms) Two forms of DED are recognized: ADDE (Aqueous Deficient Dry Eye) and EDE (Evaporative Dry Eye). 1. In ADDE: • Tear hyperosmolarity results when lacrimal secretion is reduced • Normal evaporation from the eye is present 2. In EDE: • Tear hyperosmolarity osmolarity is caused by excessive evaporation from the exposed tear film • Normally functioning lacrimal gland is present The Ocular Surface 15 (2017) 438e510 (Pathophysiology Report) 5 Diane T. Adamczyk, OD, FAAO Copyright © 2024 5 5 Ocular Surface Diesease Treatment Options Pharmacology II Circle of Dry Eye Disease Ophthalmology 2017;124:S14-S19 10 Diane T. Adamczyk, OD, FAAO Copyright © 2024 6 -many things can cause DED and this is a circle showing what can cause it such as Lasik, viral/bacteria, allergy, blepharitis, apoptosis of the conj and cornea -if you can manage and treat it, it will help with DED 6 Ocular Surface Diesease Treatment Options Pharmacology II Ocular Surface Disease • Treatment – Relieve Symptoms – Heal ocular surface – Prevent complications such as neovascularization 12 Diane T. Adamczyk, OD, FAAO Copyright © 2024 7 7 Ocular Surface Diesease Treatment Options Pharmacology II Dry Eye Treatment • • • • • • Tear Supplements Tear Conservation Tear Stimulation Anti-inflammatory Nutrition Miscellaneous other 13 Diane T. Adamczyk, OD, FAAO Copyright © 2024 8 8 Ocular Surface Diesease Treatment Options Pharmacology II Tear Supplementation Artificial Tears Lubricants 14 Diane T. Adamczyk, OD, FAAO Copyright © 2024 9 9 Ocular Surface Diesease Treatment Options Pharmacology II Lubricants • Dry eye • Corneal abrasion • Keratitis • GPC, SLK, VKC à allergic conjunctivitis putting a lubricant washes out the allergens relieves the pt • Viral à doesn’t have the best treatment but lubricant might be a better option • Others 15 Diane T. Adamczyk, OD, FAAO Copyright © 2024 10 -lubricants aren’t only for dry eyes but can be used for other ocular purposes -if a corneal abrasion is very small you don’t want to treat with a topical antibiotic but instead use a lubricant to provide pt with comfort might be adequate enough 10 Ocular Surface Diesease Treatment Options Pharmacology II Tear Supplementation • Polymer based artificial tears • Ideal artificial tear – Reproduce characteristics of natural tears 16 Diane T. Adamczyk, OD, FAAO Copyright © 2024 11 -what makes up the optical lubricant à if it can mimic our natural tears but no artificial tear does - 11 Ocular Surface Diesease Treatment Options Pharmacology II Tear Supplementation: Artificial Tear Formulation • Water based + polymer • Buffers • Tonicity and pH • Preservatives • Nutrients 17 Diane T. Adamczyk, OD, FAAO Copyright © 2024 12 -what is put in artificial tears 12 Ocular Surface Diesease Treatment Options Pharmacology II Tear Supplementation: Artificial Tear Formulation • Water based + polymer • Buffers • Tonicity and pH • Preservatives • Nutrients 18 Diane T. Adamczyk, OD, FAAO Copyright © 2024 13 13 Ocular Surface Diesease Treatment Options Pharmacology II Tear Supplementation: Artificial Tear Formulation • Polymer: – A compound formed by joining smaller molecules – Functions to • Enhance: – – – – – Viscosity Lubrication Retention time Tear stability Wettability • Decrease blink friction • Minimize surface tension – Polysaccharides are the most common polymers 19 Diane T. Adamczyk, OD, FAAO Copyright © 2024 14 -every time you blink if tears are not smooth it will be irritant to the pt 14 Ocular Surface Diesease Treatment Options Pharmacology II Tear Supplementation: Artificial Tear Formulation • Polysaccharides include: – Mucilages • An artificial sticky paste used as a vehicle or excipient • Examples: – Methylcellulose (MC), hydroxyethylcellulose, hydroxypropylcellulose, hydroxypropyl methylcellulose (HPMC), carboxymethylcellulose (CMC) – Dextrans • High molecular weight polymer of D-glucose 20 Diane T. Adamczyk, OD, FAAO Copyright © 2024 15 -mucilage's: anything “cellulose” has a good amount of viscosity allowing more staying power and vehicle for the drug bc it allows it to stay on the ocular surface for a long time 15 Ocular Surface Diesease Treatment Options Pharmacology II Tear Supplementation: Artificial Tear Formulation • Polysaccharides include: – Viscoelastic substances • Both viscous and elastic • Examples: – Sodium hyaluronate (500,000 x viscosity saline) – Chondroitin sulfate (350,000 x viscosity saline) – Vinyl Derivatives • Water soluble polymers • Increase viscosity • Examples: – Polyvinyl Alcohol (PVA) – Polyvinylpyrrolidone (PVP) • Wetting agent for CL Agents or gel solutions 21 Diane T. Adamczyk, OD, FAAO Copyright © 2024 16 16 Ocular Surface Diesease Treatment Options Pharmacology II Tear Supplementation: Artificial Tear Formulation • Water based + polymer • Buffers • Tonicity and pH • Preservatives • Nutrients 22 Diane T. Adamczyk, OD, FAAO Copyright © 2024 17 17 Ocular Surface Diesease Treatment Options Pharmacology II Tear Supplementation: Artificial Tear Formulation • Buffers – Resist a change in pH – Normal tear pH: 7.4 • Dependent on bicarbonates, proteins, phosphates, ammonium, others – Buffers include: • • • • • • Phosphate, Phosphate-acetate, Phosphate-citrate, Phosphate-citrate-bicarbonate, Borate, Sodium hydroxide 23 Diane T. Adamczyk, OD, FAAO Copyright © 2024 18 -hyperosmolarity à sucks fluid out of the cornea so not a good thing 18 Ocular Surface Diesease Treatment Options Pharmacology II Tear Supplementation: Artificial Tear Formulation • Tonicity and pH – Tonicity: measure of effective osmolarity (hyper,hypo, iso tonic) – Tonicity and pH examples: • Sodium chloride • Potassium chloride • Boric acid • Ions 24 Diane T. Adamczyk, OD, FAAO Copyright © 2024 19 -want to use something hypertonic if there is corneal edema 19 Ocular Surface Diesease Treatment Options Pharmacology II Tear Supplementation: Artificial Tear Formulation • Electrolytes – Maintain or lower osmolarity – Corneal epithelial metabolism or buffer system – Sodium chloride, potassium 25 Diane T. Adamczyk, OD, FAAO Copyright © 2024 20 20 Ocular Surface Diesease Treatment Options Pharmacology II Tear Supplementation: Artificial Tear Formulation • Water based + polymer • Buffers • Tonicity and pH • Preservatives • Nutrients 26 Diane T. Adamczyk, OD, FAAO Copyright © 2024 21 21 Ocular Surface Diesease Treatment Options Pharmacology II Tear Supplementation: Artificial Tear Formulation • Preservatives – Kill or inhibit microorganism growth – “First Generation*” • Bacteriostatic (cidal) • Includes: – – – – – Quaternary ammonium compounds (BAK*, polyquaternium) Mercurials (thimerosal*) Alcohols (chlorobutanol*) Esters of parahydroxybenzoic acid (methylparaben* and propylparaben*) EDTA* enhances quaternary ammonium base 27 Diane T. Adamczyk, OD, FAAO Copyright © 2024 22 -glaucoma are preserved with BAK in their topical agent 22 Ocular Surface Diesease Treatment Options Pharmacology II Tear Supplementation: Artificial Tear Formulation • Preservatives – Potential ADR: • Epithelial toxicity (BAK) • Tear disruption (BAK) • Allergic reaction (thimerosal) – Possible solution to ADR: • Unpreserved unit dose packages – Discard 12 hours use 28 Diane T. Adamczyk, OD, FAAO Copyright © 2024 23 23 Ocular Surface Diesease Treatment Options Pharmacology II Tear Supplementation: Artificial Tear Formulation • Preservatives – Next Generation - formulations preserved in bottle: • Break down to nontoxic substances when exposed to light or ocular surface – Stabilized Oxychloro Complex: • Sodium chlorate + light > sodium chloride + water – Sodium Perborate: • Sodium perborate + water > H202 • Sodium perborate + eye > catalase decomposes to H20 + O2 29 Diane T. Adamczyk, OD, FAAO Copyright © 2024 24 -want the cornea and conj to heal with ocular surface and lubricants 24 Ocular Surface Diesease Treatment Options Pharmacology II Tear Supplementation: Artificial Tear Formulation • Water based + polymer • Buffers • Tonicity and pH • Preservatives • Nutrients 30 Diane T. Adamczyk, OD, FAAO Copyright © 2024 25 25 Ocular Surface Diesease Treatment Options Pharmacology II Tear Supplementation: Artificial Tear Formulation • Nutrients – Vitamin A • Differentiation and maintenance of mucosal epithelium • Absence of VitA: loss of goblet cells, epithelial keratinizing metaplasia • Topical may help when goblet cells affected 31 Diane T. Adamczyk, OD, FAAO Copyright © 2024 26 -vit A deficiency can lead to loss of goblet cells so topical supplements help with goblet cells 26 Ocular Surface Diesease Treatment Options Pharmacology II 32 Diane T. Adamczyk, OD, FAAO Copyright © 2024 27 27 Ocular Surface Diesease Treatment Options Pharmacology II Various Artificial Supplements Various Formulations 33 Diane T. Adamczyk, OD, FAAO Copyright © 2024 28 28 Ocular Surface Diesease Treatment Options Pharmacology II 35 Diane T. Adamczyk, OD, FAAO Copyright © 2024 29 29 Ocular Surface Diesease Treatment Options Pharmacology II Systane lubricant family • Proprietary polymer HP-Guar (which chemically combines with borate in the pH environment of the eye to create a meshwork gel that helps to retain active lubricants on the ocular surface) • Systane COMPLETE • For all major forms of dry eye • Nano-droplet technology which helps retain lubricant on ocular surface 36 Diane T. Adamczyk, OD, FAAO Copyright © 2024 30 -HP guar creates a polymer meshwork gel and has a better staying power on the ocular surface -what it does is, it contains nanocides (small but effective) lipid droplets 30 Ocular Surface Diesease Treatment Options Pharmacology II Artificial Tears • Thera Tears (ATF) – Hypotonic solution • Decreases osmolarity – Preservative free (unit dose) – Sodium perborate (preservative) • Dissociates to H2O2 • Then to oxygen and water by tear catalase – Electrolyte balance • restores conjunctival goblet cells and promotes healing – 2-6 gtts/QID x 3 mos 37 Diane T. Adamczyk, OD, FAAO Copyright © 2024 31 -seems to really help the ocular surface à drop has to be used consistently for weeks to months to see results 31 Ocular Surface Diesease Treatment Options Pharmacology II OTC Artificial Tears: Cochrane Review 2016 Quality of Evidence: low *Cannot propose 1 OTC artificial tear superior to another 38 Diane T. Adamczyk, OD, FAAO Copyright © 2024 32 32 Ocular Surface Diesease Treatment Options Pharmacology II Other Considerations 39 Diane T. Adamczyk, OD, FAAO Copyright © 2024 33 33 Ocular Surface Diesease Treatment Options Pharmacology II Eyesol® (perfluorohexyloctane based solution) • Used in : Vevye (cyclosporine ophthalmic solution) and Miebo • Formerly NOV03 • Proprietary water free technology • Preservative free ophthalmic drop 40 Diane T. Adamczyk, OD, FAAO Copyright © 2024 34 -there are some vehicle that are soley used as ocular lubricants, not carrying the drug but are just helping the ocular surface heal -the perflurohexoloctane is the lubricant in miebo but in vevye it has both the perlurohexyloctane and cyclosporine -vevye is a vehicle but also a lubricant -miebo is the self driven vehicle bc the drop used for ocular surface attached without a drug attached which is the cyclosporine à self driving car -vevye is the same as miebo but it has the drug attached to it (cyclosporine solution) à water free technology helps make this drop preservative free so bacteria can’t grow à don’t need a huge drop a small drop spreads evenly, more is not better sometimes -miebo is the self driven vehicle bc the drop used for ocular surface attached without a drug attached à self driving car 34 Ocular Surface Diesease Treatment Options Pharmacology II Miebo (Perfluorohexyloctane Ophthalmic Solution) • Miebo – Is 100% perfluorohexyloctane drop • No water, no preservative, no other ingredients – Spreads uniformly over ocular surface, forming protective surfactant layer, preventing evaporation and sensitizing osmolarity changes – Penetrates meibomian glands – Minimal visual disturbances because refractive index is similar to water (vs gels or ointments) – Dosage: QID – Prescription only 41 Diane T. Adamczyk, OD, FAAO Copyright © 2024 35 35 Ocular Surface Diesease Treatment Options Pharmacology II Miebo (Perfluorohexyloctane Ophthalmic Solution) • Perfluorohexyloctane: – Low surface tension = strong spreading properties/rapid spread oc surface • Facilitating small drop sizes • Interacting with the lipophilic layer of tears = prevent evaporation – Semifluorinated alkane liquid – Amphiphilic (hydrophobic and hydrophilic) – Nonaqueous liquid= microbial growth is not possible, therefore no need for preservative 42 Diane T. Adamczyk, OD, FAAO Copyright © 2024 36 - 36 Ocular Surface Diesease Treatment Options Pharmacology II MEIBO (Perfluorohexyloctane Ophthalmic Solution) • NOV03 (perfluorohexloctane) – Preservative free, sterile ophthalmic solution – Inert, anhydrous semifluorinated alkane – Dual mode of action affects abnormalities in: • Lipid layer • Meibomian glands – Rapidly spreads across ocular surface because of low surface/interfacial tension – Interacts with tear film lipophilic part • Forming layer at tear film-air interface • Results: prevention of evaporation of aqueous layer – Penetrates meibomian glands: interacts and dissolves the altered, viscous meibum in the glands • SEECASE study: – RCT: NOV03 (BID or QID) compared to Saline (BID or QID) – Findings/Conclusion: • NOV03 showed benefits for signs and symptoms favoring QID 43 Diane T. Adamczyk, OD, FAAO Copyright © 2024 37 -won’t ask specifics on dosing 37 Ocular Surface Diesease Treatment Options Pharmacology II Ophthalmic Drug Delivery • Lacrisert – Hydroxypropyl cellulose ophthalmic insert – Softens within 1 hour and dissolves in 14-18 hours – Blurred vision, FB sensation – Once (twice-if needed) a day http://www.lacrisert.com/ECP (accessed 1-18-2022) 44 Diane T. Adamczyk, OD, FAAO Copyright © 2024 38 -treatment for moderate to severe dry eye -lubricant, zero order kinetic 38 Ocular Surface Diesease Treatment Options Pharmacology II Tear Conservation 45 Diane T. Adamczyk, OD, FAAO Copyright © 2024 39 -quiz 1 is up to here 39