Drugs for Common Eye Problems

1. Drugs for Common Eye Problems Cecilia A. Jimeno, M.D. Ateneo School ond Medicine & Public Health

2. Anatomy & Physiology

3. Topical Ophthalmic Drugs: Considerations • They must be absorbed into the anterior chamber • They may be administered at different frequencies depending on whether they are in ointment or solution form • Ointments: have a longer duration of action (2-4 hrs) than drops • They must be relatively easy to administer for client compliance

4. INTRODUCTION: Tips on using Ophthalmological Preparations • Ophthalmological preparations are sterile but once opened they have the potential to be contaminated • Hence, dropper tips should NOT touch any surface • Maximum volume accommodated by the lids is 30μl; usual drop size of a standard eye drop bottle is 20 μl which will stimulate tearing for 5 minutes

5. TIPS • Only one drop should be placed in the eye at a time since by sheer volume it will just spill over • Allow a 5 minute interval between 2 consecutive eye drops • Some pts cannot tolerate ointments because of blurring of vision and the deposition on the eyelids (unacceptable cosmetic appearance and discomfort)

6. TIPS • Hence, prescribe drops during the day and ointments at night • Moreover, if necessary, drops should precede ointments because the latter impedes the absorption of the former

7. KINETICS: ADME • Topical drugs exert their effect by absorption via the cornea and conjunctival vessels • Excess drug is cleared via the lacrimal apparatus through the nasal mucosa and the nasopharynx ----- access to systemic circulation [and hence, systemic side effects] • Hence, instruct patients on manual nasolacrimal occlusion and eyelid closure for 1 to 2 min to decrease systemic absorption

8. Outline (based on PNDF) • Anti-infective agents • Anti-inflammatory agents - Steroids - NSAID’s • Diagnostic agents • Drugs used in glaucoma • Cholinergics • Beta-arenoceptor blocking drugs (Beta blockers) • Adrenergic agonsts • Prostglandin analogues • Carbonic anhydrase inhibitors • Hyperosmotic agents

9. Outline 6. Local anesthetics (not included) 7. Mydriatics and Cycloplegics (Anti-cholinergics)

10. Anti-Infective Agents: general • Avoid indiscriminate use of broad spectrum antibiotics, or • The use of antibiotics for excessively long periods of time • Caution on use of combined antibiotics & steroid preparations • RATIONAL PRESCRIBING: • To prevent emergence of resistant organisms • To avoid ADR’s (toxic eye reactions) • To avoid unnecessary expense

11. Anti-Infective Agents (general principles) • For maximal effect on ocular and periocular tissues, the properly dosaged and diluted IV antibiotic preparations may also be injected through the ff routes: subconjunctival, intracameral, intravitreal and retrobulbar areas

12. Chloramphenicol • Broad spectrum, bacteriostatic against most Gm (+), Gm (-) and anaerobic organisms • Resistance is increasing esp for hospital strains of staphylococci (50%) • High lipid solubility: good therapeutic evels in the aqueous humor • No route of admin can achieve good levels in the vitreous

13. Chloramphenicol • INDICATIONS: superficial infections of the eye caused by susceptible bacteria (used only when less toxic drugs are contraindicated or ineffective) • Local drug toxicity is rare • Consider systemic absorption ff topical ophtalmic application: “gray baby” syndrome, urticaria, allergic reactions (rash), bone marrow suppression (e.g. aplastic anemia) • Pregnancy Risk: C • Eye ointments (BID-TID) or drops (hourly or q 6hrs)

14. Erythromycin • Macrolide: gram positive cocci (staph, strep) and bacilli ; some gm (-) cocci (Neisseria) & bacilli (H. Influenzae, Moraxella, Chlamydiae, Treponema) • Recommended for prevention of neonatal ophthalmia • Pregnancy Risk Category: B

15. Erythromycin (cont) • Indications • Superficial infections of the eye caused by susceptible orgs • Adjunct to oral anti-infective therapy of Chlamydia infections (trachoma, inclusion conjunctivitis) • Prophylaxis of ophthalmia neonatorum from both gonococci and Chlamydia

16. Erythromycin (cont) • Dose: as eye ointment • Bacterial infections: OD to BID • Chlamydial ophtalmic infections: BID daily for 2 mos or BD for the first 5 days of each month for 6 mos • Prophylaxis of ophthalmia neonatorum: 1 cm ribbon of 0.5% ointment into each conjunctival sac immediately after birth: new tube for each neonate (single use)

17. Oxytetracycline • Bacteriostatic against gm (-) [Pseudomaonas aeruginosa, Entorobacteriacae] and gm (+) bacteria and against Rickettsia, Chlamydia, Mycoplasma, spirochetes, fungi & viruses • Penetrate ocular tissues better than other anti-infectives because of their high lipid solubility • Same indications as Erythromycin • Systemic absorption possible : serious dental & skeletal effects • Pregnancy risk category: D • Eye ointment

18. Gentamicin • Bactericidal for gm (-) aerobic organisms through bacterial ribosomal inhibition • Limited bioavailability: After topical application , much of the drug is bound to the iris and choroidal pigment • For superficial infections of the eye caused by susceptible orgs: Pseudomonas aeruginosa, E. Coli, Enterobacter, Klebsiell, Proteus, Serratia • Pregnancy risk: C • Ointment 2-3x/d, drops q1-4 hr

19. Tobramycin • Also an aminoglycoside against gm (-) orgs • Unlike gentamicin, has poor activity against Enterococcus and Mycobacterium • When inflammation is severe, there is a combined tobramycin + dexamethasone preparation (eye drops and ointment)

20. Framycetin • Aminoglycoside closely related to the neomycin group; bactericidal & active against both gm (+) and gm(-) bacteria found in superficial eye infections (staph, Pseudomonas, coliforms, and Pneumococci) • Treatment of local eye infections (Conjunctivitis, blepharitis) due to susceptible organisms; corneal abrasions, ulers and burns • Eye drops, 1 drop 3-4x/d

21. Aciclovir • Purine analog, 1st or 2nd gen antiviral specific for local treatment of Herpes simplex keratoconjunctivitis and varicella zoster viral infection • Highly effective effective viral DNA polymerase inhibitor in affected cells • For local treatment of HSV 1 and 2, varicella zoster infections affecting eye • Apply eye ointment to cover all lesions 5x/d for 14 days to start as soon as with signs & sx

22. Ganciclovir • Purine analog much like acyclovir but differs by an additional hydroxymethyl group on the side chain with wider spectrum of activity • HSV 1 and 2, Herpes varicella-zoster, EBV • Inhibits viral DNA synthesis by competitive inhibition of viral DNA polymerase and is incorporated into viral DNA as DNA chain terminator • Has potential to cause cancer, birth defects, azospermia (unlikely for topical but possible) • Pregnancy Risk category: C

23. Trifluridine • Thymidine analog which inhibits DNA polymerase and incorporates itself into DNA • Very effective against HSV 1 and 2,and vaccinia. Inhibits CMV and adenovirus in vitro • Precaution: may impair wound healing (post-op and thinned corneas) • Pregnancy risk category: C

24. Fusidate sodium (fusidic acid) • Antibiotic derived from Fusidium coccineum • Inhibits protein synthesis in bacteria, active against a wide range of gm (+) orgs esp staphy & Strep and some gm (-) orgs (pneumococus, Neisseria, Hemophilus, Moraxella, Corynebacterium) • No known cross-resistance with other antibiotics • Stable to bacterial beta-lactamases • Penetrates well into the aqueous humor • Drops suspension: 1 drop q 12 h

25. Ofloxacin • One of the 4 quinolones, bactericidal to a large number of gm (+) and gm (-) orgs through inhibition of DNA gyrase • For Staph aureus, H. influenzae, Pseudomonas aeruginosa, E. Coli, Klebsiella & enterobacteriacae, anerobes, legionella, Neisseria gonorrhea, Chlamydia trachomatis • Pregnancy risk category: C • Eye ointment, Eye drops solution

26. Povidone-iodine (topical) • Used as an epitheolytic agent causing destruction of corneal epithelium; • Does not remove viruses or enter live cells • Cocaine inactivates this agent; should not be used for corneal anesthesia • Indicated for superficial dendritic forms of herpes simplex keratitits when aciclovir and ganciclovir are not available • Used for peri-operative preparations of the conjunctiva and periocular skin

27. Anti-inflammatory Agents STEROIDAL NSAID

28. STEROIDAL • WARNING: Intake or application of corticosteroids to the eye may induce an attack of or aggravate open angle glaucoma • Inhibit inflammatory response of whatever cause: mechanical, chemical or immunologic agents • Inhibit redness, edema, exudation, capillary dilatation, fibroblastic proliferation and fibrin deposition, and cellular infiltration & migration of leukocytes and phagocytes, collagen deposition and cicatrization

29. Steroids • Stablize lysosomal membranes with prevention of release of kinins, inhibition of prostaglandin synthesis, and with chronic use decrease Ab production • Following instillation into the conjunctival sac, corticosteroids are absorbed into the aqueous humor and systemic absorption may occur

30. STEROIDS: Indications • Corneal & conjunctival inflammation such as allergic keratoconjunctivitis, episcleritis, immune viral interstitial keratitis • To decrease inflammation and rejection in corneal transplant • For uveitis, iritis and cyclitis, scleritis • Corneal, conjunctival, and scleral injuries from chemical, radiation and thermal burns • Treatment of post-op inflammation

31. Steroids: contraindications • Microbial, viral, fungal and tuberculous infections of the eye, unless these infections are controlled by appropriate chemotherapy, and use is under close supervision of a specialist • Precaution: some preparations contain sulfite, which may cause allergic reactions • Chronic use may cause corneal perforation • Example: prednisolone, dexamethasone drops suspension

32. Combination of Antibiotics & Steroids • Sulfacetamide + Prednisolone: eye drops suspension – 10% sulfacetamide + 0.25% prednisolone (as acetate), 5 mL bottle • Tobramycin + dexamethasone: • Eye Drops Suspension: 0.3% tobramycin + 0.1% dexamethasone, 5 mL bottle • Eye Ointment: 0.3% tobramycin + 0.1% dexamethasone, 3.5 g tube

33. NSAID’s • Used for local treatment of ocular inflammation without the disadvantages of steroids • E.g. diclofenac eye drops suspension • Reduces leukocyte accumulation and exudation into the chamber fluid • Has good penetration into the ant chamber • Re-epithelialization of the corneal epithelium is not inhibited by local diclofenac treatment

34. NSAID’s: Indications • Inhibition of intra-operative miosis during cataract surgery • Treatment of macular edema • Chronic conjunctivitis, ketaoconjunctivitis, keratitis, episcleritis • Painful post-traumatic conditions of the cornea and conjunctiva • Pre-op and in short- and long-term post-operative inflammatory process, to reduce ciliary and conjunctival injection • Corneal margin ulcers

35. NSAID’s: precautions • Use with caution on pts with known bleeding tendencies, or on medications that prolong bleeding • Pregnancy risk category: B • Generally well tolerated with only mild transient burning • Examples: Nepafenac Eye Suspension: 1 mg/mL, 5 mL bottle

36. DIAGNOSTIC AGENT: Fluorescein • Yellow water-soluble dibasic that produces an intense green fluorescence in alkaline medium • An indicator dye for the diagnosis of corneal epithelial defects or abrasions, & detection of foreign bodies; for testing the patency of the nasolacrimal drainage, fitting of contact lenses, etc • IV preparation is used to study the aqueous secretion of the ciliary body; for fluorescein angiography, and vitreous fluorophotometry

37. DRUGS USED IN GLAUCOMA

38. Anatomy & Physiology

39. Flow of aqueuos humor

42. Pathophysiology of glaucoma • Increased intraocular pressure causes optic nerve damage, visual field deterioration and eventually blindness • Degree of damage depends on the level of the IOP and the chronicity of the conditio • Major therapeutic objective: reduce IOP urgently to arrest the damage to the optic nerve

43. Therapeutic options • Options for lowering IOP include • the use of topical or systemic medications, • laser trabeculoplasty, • surgery to improve outflow facility, and • cyclodestructive laser to reduce aqueous production.

44. Treatment of Glaucoma • Primary open-angle glaucoma is primarily treated medically, while angle closure glaucoma and congenital glaucoma are treated surgically, although short term drug therapy should be initiated to decrease intra-ocular pressure prior to surgery • IOP may be decreased by increasing the rate of outflow (drainage) of aqueous humor from the anterior chamber OR decreasing rate of production

45. Glaucoma Medications Used for Chronic Treatment

46. CHOLINERGIC AGONISTS (miotics) • Parasympathomimetics which duplicate the effects of acetylcholine • Exerts effects on muscarinic receptors of the ciliary body stimulating the contraction of the longitudinal muscle fibers inserting to the scleral spur which then widens the valve-like pores of the trabecular meshwork facilitating outflow of aqueous humor • Possibly also a direct effect on the cholinergic receptors of the meshwork itself

47. CHOLINERGIC AGONISTS (miotics) • Pupilary constriction is NOT an imp’t factor for pressure reduction in open-angle glaucoma but is relevant in angle closure glaucoma • Constriction of pupil pulls the peripheral iris away from the trabecular meshwork • Other effects: vasodilatation of blood vessels of the conjunctiva, iris and ciliary body & inc permeability of blood-aqueous barrier leading to vascular congestion & ocular inflammation

49. CHOLINERGIC AGONISTS (miotics) • Contraindications: cause a breakdown of the blood-aqueous barrier- they are contraindicated in pts with acute ant chamber inflammation, pupillary block glaucoma, neovascular glaucoma • Caution in elderly (miosis leads to decrease in ambient light reception/dark adaptation). • Retinal detachment may rarely occur because of the drug-induced pull on the peripheral retina as the iris-lens diaphragm is pulled forward

50. Parasympathomimetics(cholinergic agents) *Values reported are relative change (%) from baseline (peak to trough effect). Canadian Ophthalmological Society evidence-based clinical practice guidelines for the management of glaucoma in the adult eye. Can J Ophthalmol 2009;44(Suppl 1):S1S93.