Lecture 2 OcSurface Pharm 158.pdf

Ocular Surface Diesease Treatment Options Pharmacology II Other Treatment Considerations Avenova Mucolytics Hormones Tetracycline Nutritional 145 Diane T. Adamczyk, OD, FAAO Copyright © 2024 120 120 Ocular Surface Diesease Treatment Options Pharmacology II Aveno (Hypochlorous acid 0.01%) Hypochlorou...

Ocular Surface Diesease Treatment Options Pharmacology II Other Treatment Considerations Avenova Mucolytics Hormones Tetracycline Nutritional 145 Diane T. Adamczyk, OD, FAAO Copyright © 2024 120 120 Ocular Surface Diesease Treatment Options Pharmacology II Aveno (Hypochlorous acid 0.01%) Hypochlorous acid 0.01% Glass bottle - preserves the safety and efficacy of the pure HOCl (not compatible with plastic) BID 146 Diane T. Adamczyk, OD, FAAO Copyright © 2024 121 -has to be in a brown bottle in order to preserve the contents of the hypochlorous acid -OTC spray 121 Ocular Surface Diesease Treatment Options Pharmacology II Skin supports wide array of microorganisms Hypochlorous acid is a natural antibacterial – Is produced naturally as an element of immune response – During oxidative burst, HOCL with other molecules are generated as WBC respond to pathogens in the body à our body naturally does this and this is what the hypochlorous acid is mimicing 148 Diane T. Adamczyk, OD, FAAO Copyright © 2024 122 -skin has many microorganisms à can cause blpharitis, MG problems 122 Ocular Surface Diesease Treatment Options Pharmacology II Hypochlorous acid – Compound is an oxidant that kills bacteria through protein and lipid peroxidation and/or halogenation – Part of ocular hygiene product to clean lids/lashes 149 Diane T. Adamczyk, OD, FAAO Copyright © 2024 123 -hypocaloric acid interacts with the bacteria that is coming in and producing cytokines in the lids lashes and skin and the drug manages the bacteria overproduction, penetrates the biofilm killing the underlying pathogen and inactivates the lipase which is an enzyme produced by the bacteria -how can you tell there is bacterial lipase in the ocular surface? à see bubbles in the tear similar to frothing of the tears is a sign of overproduction of bacteria -people who have bacterial lipase on the ocular surface will also have DE problem as a result of that -the hypochlorous acid is basically trying to get the bacteria under control and inactivate the lipase 123 Ocular Surface Diesease Treatment Options Pharmacology II 147 Diane T. Adamczyk, OD, FAAO Copyright © 2024 124 -purpose of avenova is to break the cycle of lipase that turns into soap in the tear flim aka saponification which is the degrading the lipid layer 124 Ocular Surface Diesease Treatment Options Pharmacology II Mucolytic Agents Acetylcysteine (10%, 20%) à formulated into a drop – Softens mucous – Intracellular effect on goblet cells – Use: Bronchopulmonary conditions à when drug is used for systemic purposes Filamentary keratitis, VKC, GPC (dilute to 2-5%) – Decrease viscosity – Sting 150 Diane T. Adamczyk, OD, FAAO Copyright © 2024 125 -DE can have mucoid type of discharge à would use mucolytic agent but it is a bit more extreme and is not used frequently -drop comes in contact with the eye it’s mechanism breaks up the mucus however this is a specially made drop so its not OTC 125 Ocular Surface Diesease Treatment Options Pharmacology II Other Treatments Oral tetracycline – Posterior blepharitis --- inflammatory nature à used for deep MG issues – Inhibit matrix metalloproteinases Topical role for tetracycline?---to be determined, there are no studies as of yet 151 Diane T. Adamczyk, OD, FAAO Copyright © 2024 126 126 Ocular Surface Diesease Treatment Options Pharmacology II NUTRITIONAL CONSIDERATIONS 152 Diane T. Adamczyk, OD, FAAO Copyright © 2024 127 -a lot of controversy 127 Ocular Surface Diesease Treatment Options Pharmacology II Nutrition Considerations Dry Eye Inflammatory Component Considerations: – Omega 3 May affect clotting time (decrease platelet aggregation)– therefore use with caution and appropriate comanagement (clotting time monitored) with patients on blood thinners – Flax seed oil - Reduces T lymphocyte proliferation 153 Diane T. Adamczyk, OD, FAAO Copyright © 2024 128 -literature is considering if omega 3 is the answer to heart disease, dementia, DED and some stuff it helps some it doesn’t -omega 3 has an effect on blood thinners such as coumadin so pt will bleed more 128 Ocular Surface Diesease Treatment Options Pharmacology II EPA=eicosapentaenoic acid TheraTears web site DHA=docosahexaenoic acid 154 Diane T. Adamczyk, OD, FAAO Copyright © 2024 129 -omega-3 are the good guys à break down into alpha-linolenic acid which is flax seed oil and breaks down into EPA and that breaks down further into anti-inflammatory -omega 6 breaks down into linoleic acid then into gamma linolenic acid which further breaks down into two components of anti inflammatory and pro-inflammatory which is the arachidonic acid cycle -omega 3 and 6 sometimes are taken together bc when taken together it blocks the pro inflammatory arachidonic acid aspect of omega 6 129 Ocular Surface Diesease Treatment Options Pharmacology II Considerations When Taking Omega-3 Supplements Cautions in patients with or taking: – Phenothiazines + Evening primrose oil (omega 6) à may lower seizure threshold and precipitate seizures – Blood thinners or aspirin + omega 3 and 6 (per PI) à reduces blood platelet aggregation so don’t take coumadin or aspirin – Flaxseed oil (omega 3) increases stool bulk and frequency, may cause intestinal blockage à not recommended in Bowel obstruction, irritable bowel syndrome, diverticular disease – Pregnancy category C per product information 155 Diane T. Adamczyk, OD, FAAO Copyright © 2024 130 -pt who has epiliepsy à should avoid taking these supplements 130 Ocular Surface Diesease Treatment Options Pharmacology II Omega and Blood Thinning EPA and DHA >3g/day may increase prothrombin time and risk of bleeding Omega 3 may lower thromboxane A2 supplies in platelets and decrease clotting factor VII – EPA specifically inhibits platelet aggregation – Therefore can consider using only DHA as an option 156 Diane T. Adamczyk, OD, FAAO Copyright © 2024 131 131 Ocular Surface Diesease Treatment Options Pharmacology II Nutrition and the Eye Suggested Use: total of four capsules daily, with meals (two capsules twice daily). 157 Diane T. Adamczyk, OD, FAAO Copyright © 2024 132 -ex of hydroeye -versions of one of the supplements 132 Ocular Surface Diesease Treatment Options Pharmacology II 158 Diane T. Adamczyk, OD, FAAO Copyright © 2024 133 133 Ocular Surface Diesease Treatment Options Pharmacology II Background: use of n-3 fatty acid supplements for DED treatment Methods: Each active capsule: ◦ 400 mg of EPA and 200 mg of DHA, ◦ for a total daily dose of 2000 mg of EPA and 1000 mg of DHA Each placebo capsule: ◦ 1000 mg of refined olive oil (68% oleic acid, 13% palmitic acid, and 11% linoleic acid) Active and placebo capsules contained: ◦ 3 mg of vitamin E (alpha-tocopherol), as an antioxidant, ◦ As well as masking flavor and lemon flavor 159 Diane T. Adamczyk, OD, FAAO Copyright © 2024 134 -dream study à are the omega going to help with DE problem -won’t ask about this 134 Ocular Surface Diesease Treatment Options Pharmacology II Methods Each active capsule: – 400 mg of EPA and 200 mg of DHA, – for a total daily dose of 2000 mg of EPA and 1000 mg of DHA Each placebo capsule: – 1000 mg of refined olive oil (68% oleic acid, 13% palmitic acid, and 11% linoleic acid) Active and placebo capsules contained: – 3 mg of vitamin E (alpha-tocopherol), as an antioxidant, – As well as masking flavor and lemon flavor 160 Diane T. Adamczyk, OD, FAAO Copyright © 2024 135 135 Ocular Surface Diesease Treatment Options Pharmacology II 161 Diane T. Adamczyk, OD, FAAO Copyright © 2024 136 136 Ocular Surface Diesease Treatment Options Pharmacology II 162 Diane T. Adamczyk, OD, FAAO Copyright © 2024 137 -in short, they didn’t find difference between the omega and placebo (olive oil) 137 Ocular Surface Diesease Treatment Options Pharmacology II 163 Diane T. Adamczyk, OD, FAAO Copyright © 2024 138 -the study said “they’re (omega-3) no better than olive oil” à means its no better than olive oil but not taking omega is not any better à impt keypoint 138 Ocular Surface Diesease Treatment Options Pharmacology II Considerations – More patients in treated group vs placebo – Is the placebo truly a placebo? – Patients still using other treatments (how does that affect outcomes?) 164 Diane T. Adamczyk, OD, FAAO Copyright © 2024 139 139 Ocular Surface Diesease Treatment Options Pharmacology II Purpose DREAM Extension Study: Determine effects of continued vs discontinued use of omega-3 supplements (placebo = refined olive oil) Method: Those who received omega 3 supplement as part of the primary DREAM trial for 12 months, were then randomized for an additional 12 months to continue with the omega 3 supplements or be given a placebo 165 Diane T. Adamczyk, OD, FAAO Copyright © 2024 140 -extension study à take pt off omega and if it makes a difference à there was no difference between the two groups 140 Ocular Surface Diesease Treatment Options Pharmacology II What is the difference? (Dream Extension 2020) 166 Diane T. Adamczyk, OD, FAAO Copyright © 2024 141 141 Ocular Surface Diesease Treatment Options Pharmacology II Conclusions Findings: No significant differences/similar findings between both groups: Ocular Surface Disease Index score, conjunctival staining, corneal staining, Results from 2 DREAM clinical trials does not support a beneficial effect of omega 3 supplementation on DED Conclusion: Patients discontinuing use of omega 3 did not have significantly worse outcomes compared to those who continued using omega 3 supplements 167 Diane T. Adamczyk, OD, FAAO Copyright © 2024 142 142 Ocular Surface Diesease Treatment Options Pharmacology II 168 Diane T. Adamczyk, OD, FAAO Copyright © 2024 143 143 Ocular Surface Diesease Treatment Options Pharmacology II 169 Diane T. Adamczyk, OD, FAAO Copyright © 2024 144 -each individual study favors the omega 3 -study on bottom left is comparing the omega 3 and the placebo and its effect on DE showing that it favors the omega 3 -study on bottom right is showing individuals who took placebo or omega 3 and their Schirmer's test after taking the supplement and it either shows favoring omega 3 or no difference between the placebo and omega 3 144 Ocular Surface Diesease Treatment Options Pharmacology II Omega-3 and Omega-6 for DED Main Results: Although much evidence was uncertain, long-chain omega-3 supplements may have little to no benefit relative to placebo on DE symptoms BUT did improve some clinical signs Beneficial effect on symptoms when omega-3 supplements combined with standard dry eye tx (e.g. artificial tears, warm compresses, steroids) vs standard treatment alone For combined omega-3 and omega-6 supplements, relative to placebo, no benefit for tear production, but small amount of improvement in tear stability OVERALL: review suggest possible role for long-chain omega- 3 supplementation in managing DED, although evidence is uncertain and inconsistent 170 Diane T. Adamczyk, OD, FAAO Copyright © 2024 145 -main results of previous slides studies -highlighted is the main point 145 Ocular Surface Diesease Treatment Options Pharmacology II Note differences which can affect efficacy: In doses Sources of omega-3 E.g. Fish oil rich in EPA and DHA versus flaxseed oil which contains short chain ALA Nutrients 2020, 12, 952; doi:10.3390/nu12040952 171 Diane T. Adamczyk, OD, FAAO Copyright © 2024 146 -point is that study is very heterogenous bc the study used diff omega 3 at diff concentrations and pt were taking other supplements -there’s variability which is the issue 146 Ocular Surface Diesease Treatment Options Pharmacology II Symptom Score Schirmer TBUT Fluorescein Stain Cornea Volume 38, Number 5, May 2019 Considerations: *Most studies very controlled (vs DREAM: allowed other Tx) *Variability in diet may affect results (location example) Conclusion: May recommend Omega 3 supplement for DED 172 Diane T. Adamczyk, OD, FAAO Copyright © 2024 147 147 Ocular Surface Diesease Treatment Options Pharmacology II 1000-3000 mg EPA/DHA per day (within therapeutic dosage) Caution above 3000mg EPA/DHA with elderly and blood thinners, hemophilia also Omega 3 Considerations Check bp on patients taking HT meds – high dose omega-3 may have hypotensive effect Omega 3 may lower blood pressure and may increase effect with bp meds Avoid fish or fish oil on day before to day after chemotherapy – has chemotherapy negating effect May take 3-6 months for maximum omega 3 blood level Obtain baseline omega 3 level prior to starting regimen 175 Diane T. Adamczyk, OD, FAAO Copyright © 2024 148 -high dose of omega 3 can have an effect on bp 148 Ocular Surface Diesease Treatment Options Pharmacology II OTHER 176 Diane T. Adamczyk, OD, FAAO Copyright © 2024 149 149 Ocular Surface Diesease Treatment Options Pharmacology II Neurotrophic Keratitis Neurotrophic keratitis: a degenerative corneal disease caused by damage of trigeminal innervation, resulting in reduction (hypoesthesia) or loss (anesthesia) of corneal sensitivity. – Corneal denervation can result in: Reduction in lacrimal reflex/vitality and epithelial breakdown Corneal edema, ulceration, melting, perforation – Corneal homeostasis is interplay between corneal nerves and epithelial cells mediated through production of trophic factors (e.g. neuromediators and nerve growth factor) 177 Diane T. Adamczyk, OD, FAAO Copyright © 2024 150 -something that is affecting the corneal innervation -in herpes simplex or someone gets splashed with acid can affect corneal nerves and decrease sensitivity 150 Ocular Surface Diesease Treatment Options Pharmacology II Neurotrophic Keratitis Most common causes: – Herpes keratitis, – Chemical burns, – Long-term use of contact lenses, – Corneal surgery, – Chronic severe blepharitis, – Diabetes Signs of neurotrophic keratitis 178 Diane T. Adamczyk, OD, FAAO Copyright © 2024 151 -neurotrophic keratitis is rare but know that it is out there 151 Ocular Surface Diesease Treatment Options Pharmacology II Neurotrophic Keratitis Treatment – D/C meds that can cause NK – Artificial tears – Corneal or scleral CL – Amniotic membrane – Tarsorrhaphy à sowing of lateral canthus of the upper and lower lids so there is less exposure to the ocular surface – Autologous serum with growth factors – Topical NGF (Cenegermin) 179 Management of neurotrophic keratitis. www.co-ophthalmology.com Vol 32 (Number 4) July 2021 Diane T. Adamczyk, OD, FAAO Copyright © 2024 152 -these are ways to prevent the pt from getting neurotrophic keratitis 152 Ocular Surface Diesease Treatment Options Pharmacology II Oxervate (cenegermin-bkbj ophthalmic solution) 0.002% 1st FDA approved treatment for neurotrophic keratitis Escherichia coli derived recombinant form of human nerve growth factor Structurally identical to nerve growth factor naturally produced by eyes Mechanism of Action of Nerve Growth Factor: – Is an endogenous protein involved in the differentiation and maintenance of neurons – Acts through specific nerve growth factor receptors in the anterior segment of the eye – To support corneal innervation and integrity 180 Diane T. Adamczyk, OD, FAAO Copyright © 2024 153 -oxervate is a treatment and management of the neurotrophic keratitis -biological mean is coming from e.coli and it’s mimicking the nerve growth factor that is in our eye naturally to help regenerate those nerves and grow back - 153 Ocular Surface Diesease Treatment Options Pharmacology II Oxervate (cenegermin-bkbj ophthalmic solution) 0.002% Dosage: one drop 6 times/day at 2 hour intervals for 8 weeks No CL or other eye drops for at least 15 minutes Adverse Effects: – Pain on instillation (16%). Ocular hyperemia, ocular inflammation, tearing, fb sensation, corneal deposits Shipped directly to home (insulated packed with dry ice) Refrigerate within 5 hours of delivery Cost: Oxeívate is aíound $25,418.76, 12% off the aveíage íetail píice of $29,141.35 (1-30-22) – (on line 1-16-23: $70,000) 181 Diane T. Adamczyk, OD, FAAO Copyright © 2024 154 -biologics are typically given IV or IM not really topically bc of its instability - 154 Ocular Surface Diesease Treatment Options Pharmacology II Conclusion: Topical rhNGF is safe and more effective than vehicle in promoting healing of moderate to severe NK 182 Diane T. Adamczyk, OD, FAAO Copyright © 2024 155 -study shows that oxervate works well and there is cloudiness to the cornea but is still able to heal 155 Ocular Surface Diesease Treatment Options Pharmacology II SUMMATION 183 Diane T. Adamczyk, OD, FAAO Copyright © 2024 156 156 Ocular Surface Diesease Treatment Options Etiology Lubricants (the components) Lacrimal Occlusion Tears Stimulation – – – Collagen/Extended dissolvable/Silicone /Smart Plug Adverse effects Candidates – – – Pilocarpine, Cevimeline, Diquafosol iTear 100 Tyrvaya (varenicline) – – Steroids Cyclosporine 0.05% (Restasis) Emulsion Expectations (1 month-dec symptoms, 3 months - improvement, 6 months - maintenance) Pharmacology II Ocular Surface Review Anti-inflammatory – Cyclosporine 0.09% (Cequa) Nanomicelle Improvement as early as 28 days – Cyclosporine 0.1% (Verkazia) – Cyclosporine 0.1% (Vevye) – Lifitegrast (Xiidra) Other – Miebo (perfluorohexyloctane ophthalmic solution) – Mucolytics/Hormones/Nutrition (Omega 3) – Oxervate 184 Diane T. Adamczyk, OD, FAAO Copyright © 2024 157 157 Ocular Surface Diesease Treatment Options Pharmacology II Conclusions Many Causes of Dry Eye Many Therapeutic Approaches Multiple Deficiencies within same patient Combination Therapy Anti-inflammatories Anti-evaporatives Secretagogues Improved Polymers Mucomimetics 185 Diane T. Adamczyk, OD, FAAO Copyright © 2024 158 158