Outline Neo/Poly/Dex and Beyond: What ophthalmology essen:als to stock in your pharmacy and how to use them! Dr. Kimberly Hsu, DVM, MSc, DAVCO Eye Care For Animals St. Charles, IL 630-444-0393 stcharlesinfo@eyecareforanimals.com Introduc:on Topical An:bio:cs Medica:ons for KCS, Immune-Mediated Ocular Surface Disease Topical An:-inflammatories Topical An:-Glaucoma Medica:ons Ophthalmic Medica:on Toolkit Consider stocking in your clinic Be able to readily script out: Ointment vs. Drops Bacitracin/Neomycin/Polymixin Ini:al treatment for simple corneal ulcers as prophylaxis Terramycin Conjunc:vi:s in cats Neo/Poly/Dexamethasone Ocular surface immune-mediated disease, conjunc:vi:s, KCS, mild to moderate uvei:s Latanoprost Consider stocking if you see ER cases, acute primary glaucoma crisis cases O_en works in <1h! Dorzolamide Consider stocking if you see ER cases, acute glaucoma crisis Longer onset BUT can use with anterior lens luxa:on, uvei:s, etc. Tobramycin and Ofloxacin Deep or infected corneal ulcers, corneal abscesses Diclofenac or Flurbiprofen First line therapy lens-induced uvei:s (immature cataracts or more advanced) Adjunct therapy for uvei:s Prednisolone Acetate Moderate to severe uvei:s (beeer intraocular penetra:on than Neo/Poly/ Dex) Cyclosporine or Tacrolimus Ocular surface immune-mediated disease, KCS, etc. Cidofovir FHV-1 cats Famciclovir (tablets) FHV-1 cats Timolol An:-glaucoma medica:on, least potent Ocular lubricant OINTMENT Ointments stay on ocular surface for longer :me Soothe ocular surface in condi:ons such as KCS More difficult for owners to administer Wasteful Rice grain size strip is enough Ointments will melt and disperse over en:re ocular surface Wait at least 10-15 minutes in between ointments NOT IF THERE IS A DESCMETOCELE or ruptured corneal ulcer DROPS Drops easier to administer Some medica:ons only come in solu:ons Wait at least 5 minutes in between drops The eye can only accommodate one drop 1
Topical An:bio:cs Classifica:on of An:bio:cs Why? (goal of treatment) Prophylac:c vs. Therapeu:c Organisms of Concern Target your therapy (culture?) Topical vs. Systemic Mostly topical but consider systemic if bacterial blephari:s or endophthalmi:s suspected Development of Resistance Poten:al for adverse reac:on/toxicity BacteriostaDc Chloramphenicol Macrolides Sulfonamides Tetracyclines Trimethoprim Bactericidal Aminoglycosides Bacitracin Cephalosporins Fluoroquinolones Gramidicin Penicillins Polymixin C Vancomycin General Rules: Topical An:bio:cs Most pathogens on ocular surface are Gram + Most common causes of keratomalacia are Pseudomonas Hemoly:c Streptococcus Broad spectrum an:bio:c therapy if corneal mel:ng is noted!!! Frequency Prophylaxis= BID-TID (TID if superficial ulcer present) Infec:on=at least 4-6 :mes a day, up to q1h Common Topical Ocular An:bio:cs NPG (Neomycin/Polymyxin/Gramidicin) BNP (Bacitracin/Neomycin/Polymyxin) Ofloxacin/Ciprofloxacin Gentamicin/Tobramycin Chloramphenicol Oxytetracycline Erythromycin 2
Aminoglycosides: Neomycin, Gentamicin, Tobramycin Affect bacterial protein synthesis: 30S ribosome Strong Gram nega:ve spectrum Pseudomonas, Proteus, E.Coli, Enterobacter Excep:on: Neomycin ineffec:ve against Pseudomonas Minimal Gram + spectrum so not great for prophylaxis No anaerobes Neomycin No corneal penetra:on if epithelium intact Prophylaxis in superficial corneal ulcera:ons Non specific treatment of ocular surface infec:ons Good Gram nega:ve ac:vity but NO PSEUDOMONAS Contact hypersensi:vity Controversial in cats? BNP and NPD Idiosyncra:c reac:on in cats Medica:ons Neomycin is combined with (BNP, NPG) Gramidicin Alters cell membranes Gram + Stable in solu:on Bacitracin Inhibits cell wall synthesis Gram + No transcorneal penetra:on Not good for deep infec:ons Hypersensi:vity Not stable in solu:on Polymyxin B Ca:onic surfactant: interacts with phospholipids on cell surface Gram nega:ve including Pseudomonas! Poor transcorneal penetra:on Hypersensi:vity USES Non-infected superficial corneal ulcers (simple ulcers) Non-specific ocular surface infec:on BNP and NPG LIMITATIONS Poor corneal penetra:on Broad spectrum but limited ac:vity against Pseudomonas BNP only in ointment form 3
Tobramycin/Gentamicin Infec:ous kera::s with Gram nega:ve infec:on Effec:ve vs. Pseudomonas in dogs (but growing resistance in horses) Limited use in prophylaxis due to limited gram + spectrum Limited transcorneal penetra:on in intact cornea, therapeu:c levels reached with ulcers Can inhibit epithelializa:on Fluoroquinolones Bactericidal Inhibit DNA synthesis Also may poten:ally slow re-epithelializa:on Ciprofloxacin/Ofloxacin/Moxifloxacin Uses for Tobramycin and Ofloxacin Ciprofloxacin & Ofloxacin: 2 nd generadon Gram nega:ve, including Pseudomonas Good Gram + ac:vity Intraocular penetra:on into the cornea & anterior chamber Ciprofloxacin doesn t penetrate as well Ciprofloxacin may s:ng more due to lower ph Moxifloxacin: 4 th generadon Gram but more Gram + Less efficacy against Pseudomonas Superior intraocular penetra:on Ex. Hypopyon Ex. Stromal abscesses No preserva:ves O_en used in combina:on Ofloxacin should be considered if: Ac:ve corneal infec:on (keratomalacia) Corneal abscesses In cases where there could be infec:on within the globe/globe is compromised Corneal perfora:on (descemetocele) Trauma such as dog bite/cat claw wound to the eye Start these pa:ents on systemic an:bio:cs at the same :me Despite lack of Gram + spectrum, Tobramycin o_en used for Anterior stromal corneal ulcers Following debridement for indolent corneal ulcers (increased infec:on risk) Cats with herpe:c ulcers who won t tolerate an ointment 4
Oxytetracycline Inhibit bacterial protein synthesis: 30S ribosome Spectrum of ac:vity Chlamydophila, Mycoplasma Moraxella, Borrelia, Rickeesial Gram + resistance may be increasing NO PSEUDOMONAS Good op:on for cats with conjunc:vi:s! Ok for superficial herpe:c ulcers but may need to broadened spectrum Possible inhibi:on of MMPs; Accelerate healing in indolent corneal ulcers? Reduce keratomalacia (but ointment should not be used if risk of corneal rupture) Polymyxin reac:on? Erythromycin Macrolide Ointment Inhibits bacterial growth: 50S ribosome Gram-posi:ve except enterococci. Mycoplasma spp and Chlamydophila spp, along with Borrelia burgdorferi. Good op:on for cats An:bio:c Toolkit BNP ointment Superficial corneal ulcers, non-specific infec:on Helps to lubricate Tobramycin (2 nd line) or Ofloxacin (3 rd line) Deeper or infected corneal ulcers Terramycin or Erythromycin Conjunc:vi:s in cats Tear S:mulants and Subs:tutes Improve aqueous tear produc:on and tear quality Improve ocular comfort Improve ocular clarity Oral cephalosporin if ruptured or high risk of corneal rupture Increased spectrum of oral an:bio:cs (ie. Clavamox, Baytril) if cat claw, penetra:ng plant foreign body, etc. 5
Tear Subs:tutes Subs:tutes Goal is to mimic natural precorneal tear film Comfortable ph Good surface tension (efficiently cover cornea) Minimize preserva:ves Most are water-based Gel rather than drop preferred (longer dura:on) Top Picks for Subs:tute Water Soluble Gels Early KCS; quan:ta:ve KCS cases while tear s:mulants kick in; mild lubrica:on (ie. eyelid mass) Aven:x Op:xcare (carbomer [green] +/- hyaluron [purple]) Novar:s Genteal Gel Severe (HPMC) Ointment Severe KCS; heavy lubrica:on (ie. ectopic cilium) Paralube or Lacrilube Hyaluronic Acid (mucin subsdtute) Remend Lubrica:ng Drops (cross-linked hyaluronic acid) Clinical Uses for Tacrolimus and Cyclosporine Mechanisms of Ac:on KeratoconjuncDviDs Sicca Increase aqueous tear produc:on Lymphocy:c plasmacy:c lacrimal gland inflamma:on Direct lacrimos:mulant Improve tear quality Effect on goblet cells? Other Ocular Surface Disease May reduce corneal angiogenesis O_en reduces or stabilizes corneal pigment May reduce corneal lipid Pannus (Chronic Superficial Kera::s) Immune-mediated kera::s Immune-mediated conjunc:vi:s & episcleri:s Cyclosporine Source - fungus Tolypocladium inflatum Binds to cyclophillin Inhibits prolifera:on & ac:va:on of T-lymphocytes May inhibit mast cells Inhibits fibroblasts and is directly lacrimomime:c Available as Op:mmune (0.2% ointment) 1-2% compounded oil solu:on Tacrolimus Macrolide an:bio:c from Streptomyces tsukubaensis Bind to FK-binding protein Similar mechanism to CSA 10-100X more potent than cyclosporine Available in compounded 0.02-0.03% ointment, oil or aqueous solu:on 6
Tacrolimus and Cyclosporine An:-Inflammatories Both Tacrolimus and Cyclosporine o_en tapered: TID > BID > q24h, eod, twice weekly, etc. Most quan:ta:ve KCS pa:ents need BID long-term Tear produc:on begins to decrease within 24h a_er discon:nua:on but a couple of skipped doses in well-controlled pa:ents does not typically lead to relapse of signs Can be used in the face of corneal ulcera:on May be associated with decrease in number of microorganisms a_er treatment No significant effect on corneal wound healing For KCS (and likely other immune-mediated diseases), take 2-4 weeks to start seeing an effect, o_en 3-4 months for effect to plateau O_en used in conjunc:on with Neo/Poly/Dex, BNP-HC, etc., which provide faster ac:ng an:-inflammatory effects NSAIDS Diclofenac (Voltaren) Flurbiprofen Cor:costeroids Pred Acetate Pred Phosphate Dexamethasone Phosphate Neo/Poly/Dex BNP-Hydrocor:sone Frequency of use will depend on the severity of disease Can be from 4-6 :mes and as low as twice a week NSAIDS NSAIDS Author s first line treatment for non-surgical cataracts (immature or more advanced) to address subclinical lens-induced uvei:s Reduces risk of secondary glaucoma and need for enuclea:on O_en not sufficient enough alone to treat moderate to severe uvei:s Can increase IOP in the face of uvei:s Can promote MMP produc:on which can worsen keratomalacia Cau:on or avoid with a stromal ulcer Can cause direct ocular surface irrita:on Diclofenac Voltaren More potent compared to Flurbiprofen Flurbiprofen Less dura:on of ac:on More frequent administra:on to treat uvei:s 7
Cor:costeroids Cor:costeroids Generally more potent than NSAIDs for inflamma:on Rule out corneal ulcera8on before using topical cor8costeroids as they delay epithelializa8on Okay to use in a diabe:c pa:ent Frequency usually limited to no more than QID Try to taper Prednisolone Acetate has superior an:- inflammatory when compared to phosphate Prednisolone Acetate 1% suspension Pred Acetate is the most effec:ve drug for anterior uvei:s Other drugs such as Durezol can be used - very expensive Dexamethasone More potent than prednisolone but does not penetrate cornea well Clinically works well for mild to moderate uvei:s only Mostly used to treat superficial inflammatory disease KCS, episcleri:s, immunemediated kera::s, conjunc:vi:s Usually used as Neo/Poly/Dex suspension or ointment or Dexamethasone 0.1% suspension Ocular Hypotensive Agents Carbonic Anhydrase Inhibitors: Dorzolamide (Trusopt) Brinzolamide (Azopt) Methazolamide: oral Prostaglandin Analogues: Latanoprost (Xalatan) Travoprost (Travatan) Beta-blockers (Timop:c): Timolol Glycerin: oral Mannitol: IV Canine Breeds Predisposed to Glaucoma Arc:c breeds * Bassee hound * Chow Chow * Beagle Boston terrier Bouvier de flandres Bullmas:ff Cairn terrier (other terriers too) Cocker spaniel * Shiba Inu 8
Assess Your Pa:ent Treat aggressively and quickly due to threat to vision IOP lowering effect: latanoprost > dorzolamide > :molol +/- topical steroid Hospitalized: IV Mannitol Is pa:ent blind? How long has pa:ent been blind? Is a lens luxa:on present? Is this primary vs. secondary glaucoma? Is there uvei:s? Carbonic Anhydrase Inhibitors Decrease the produc:on of aqueous humor Dorzolamide 2%: Trusopt BID-TID 20-25% reduc:on in IOP Author o_en uses this for prophylaxis of contralateral visual eye in cases of primary glaucoma Brinzolamide 1%: Azopt Difference in ph makes this drug less irrita:ng May be less effec:ve in cats O_en $$$ BID-TID Dorzolamide/Timolol: Cosopt BID medica:on (Methazolamide) Oral: very expensive now Systemic side effects: electrolyte was:ng and subsequent acidosis Prostaglandin Analogues Xalatan: Latanoprost Up to 60% reduc:on in IOP Travatan: Travoprost Cause miosis and mild uvei:s Increases ou low from ICA and uveosceral ou low Most potent an:-glaucoma medica:on Effect o_en seen in <1 hour Contraindicated Anterior lens luxa:on Lens entrapment Uvei:s (last resort?) Poor choice for feline glaucoma Q24h (in PM) to TID Timolol 0.25% or 0.5% Non-selec:ve Beta Blocker Decreases produc:on of aqueous humor Wimpy an:-glaucoma medica:on on its own Typically 15-20% reduc:on in IOP Use with cau:on in cardiac pa:ents Monitor heart rate especially in smaller pa:ents» Up to 10-15% reduc:on in heart rate Use with cau:on in cats with asthma Combined with Dorzolamide: Cosopt Used for its addi:ve effect BID medica:on Consider 0.25% in pa:ents < 20lb 9
IV and Oral An: Glaucoma Meds Mannitol Use with cau:on in cardiac and renal pa:ents Use with cau:on in severe uvei:s causing glaucoma 1 gram/kg IV with filter Give slowly over 30 min No water for 4-6 hours Lasts about 3-5 hours Reduces IOP within 15 minutes Oral Glycerin Cheap Send home with owner in case of acute vision loss Instruc:ons Weight in lbs x0.75 Can mix with ½ to ¼ cup of milk Give over 15-20 minutes No food or water for 4 hours, then slowly introduce water May produce hyperglycemia Avoid in diabe:cs Reduces IOP within 10 minutes, lasts up to 10 hours Prophylac:c Treatment Miller: Dem Br/Gentamicin/Betamethasone vs. Betaxolol both delayed onset of glaucoma to 30-31m vs. 8m without tx in dogs with primary glaucoma Dees et. al: Time to medical failure not significant between hypotensive medica:ons but es:mated :me to failure with an:-inflammatory meds was longer (324d) vs. without (195d) Vet Ophthalmol. 2014;17(3):195 200. J Am Anim Hosp Assoc. 2000 Sep-Oct;36(5):431-8. 10