Medical treatment of primary open angle glaucoma

this slide show has highlighted about medical treatment of glaucoma

1. Treatment of PRIMARY OPEN ANGLE GLAUCOMA

2. Goals of Therapy Lowering intraocular pressure (IOP) has been shown to reduce the risk of glaucomatous progression of visual field loss and/or optic disc changes and is the primary goal of therapy.

3. Two Approaches : Medical Surgical

4. Classification of the Drugs Drugs increasing uveoscleral outflow:- Prostaglandin F2alpha analogues Alpha-2-agonists Drugs decreasing Aqueous production:- Beta-Blockers Alpha-2-agonists Carbonic anhydrase inhibitors Drugs increasing trabecular outflow:- Parasympathomimetics Non-Selective Agonists Prostaglandin F2alpha analogues

5. Principles of Medical Therapy 1 st line- Prostaglandin F2alpha analogues Beta-Blockers 2 nd line- alpha- agonists Prostaglandin F2alpha analogues Topical Carbonic anhydrase inhibitors Pilocarpine 3 rd line- Pilocarpine Alpha-agonists Systemic Carbonic anhydrase inhibitors

6. Prostaglandin F2alpha analogues Mechanism of Action- It acts by increasing the uveoscleral outflow by possibly increasing the permeability of tissues in the ciliary muscle or by an action on the episcleral vessels. It also increases trabecular outflow Duration of action- 24 hours Peak effect and wash out period- 2 weeks( stabilizes at 6 weeks) 6 weeks

7. Latanoprost (0.005%) A selective agonist of FP prostanoid receptor and enhances outflow mainly through uveoscleral route . Given at bedtime , OD and is superior to timolol . Produces an additive reduction of IOP of 14- 28% when combined with timolol . Travoprost (0.004%)- similar to latanoprost except it is more effective in black patients. Conjunctival hyperemia in 50% of patients and tends to subside with time.

8. Bimatoprost (0.03%) Synthetic analogue , structurally similar to Prostaglandins. Lowers IOP by increasing flow through both uveoscleral and trabecular routes. OD dose at bedtime , may cause conjunctival hyparemia but few headaches and iris hyperpigmentation . Tafluprost (0.0015%)- synthetic analogue and acts through the FP receptor. OD dose at bedtime. ( first available in preservative FREE form)

9. Side-Effects Systemic:- Local:- Skin rash Skin hyperpigmentation Iris Hyperchromia Conjunctival hyperemia and foreign body sensation. Reactivation of herpetic keratitis . Cystoid macular edema in pseudophakic and aphakic patients. Eyelash lengthening , thickening and hyperpigmentation .

10. Iris Hyperchromia

11. Lengthening of Eyelashes

12. Eyelid Pigmentation

13. Beta-Blockers They are drugs that antagonise the effects of catecholamines at beta receptors which are mainly of two types:- Beta-1 receptors are located in the myocardium and give rise to tachycardia and increased cardiac output when stimulated. Beta-2 receptors are located in the bronchi and ciliary epithelium. stimulation causes bronchodilatation and increased aqueous production. Non- selective Beta-Blockers are equipotent at beta 1 and beta2 receptors, while cardioselective are more potent at Beta-1 Receptors. The advantage of the later, atleast in theory is that broncoconstrictive effect of Beta-2 blocade is minimised . Betaxolol is the only cardioselective agent used.

14. Mechanism of action Beta blockers reduce IOP by decreasing aqueous secretion, irrespective of the state of the angle. In approximately 10% of the cases, the pressure response decreases with time: tachyphylaxis . This may occur within a few days of starting treatment (‘short term escape’) or within a few months (‘long term drift’). A combination with the topical carbonic anhydrase reduces the IOP by 15% additionally and the combination with PG analogue the reduction is even greater (20%). Duration of Action – 12 hours Peak effect and wash out period-4-6 weeks and 4-6 weeks.

15. Preparations Timolol is available in three forms; 0.25% and 0.50% used BD 0.25% and 0.50% L A used OD 0.1% gel OD or BD Betaxolol 0.5% BD has less hypotensive effect them Timolol , but the effect on the preservation of the visual field may be superior. It increases optic disc blood flow probably because of a calcium channel blocking effect on the microcirclation on the disc. Levobunolol 0.5% daily or BD Carteolol 1%, 2% BD and exhibits intrinsic sympathomimetic activity. It has a more selective action on the eye then on the cardiopulmonary system and causes less bradycardia then timolol . Metipranolol0.1%, 0.3% bd and causes occasional granulomatous uveitis and is available only in preservative free units.

16. Side effects Sytemic Local Bradycardia , asthma, hypotension, broncospasm , dyspnea , impotence , insomnia, hypoglycemia Allergic blepharoconjunctivitis , dry eye, corneal anesthesia

17. Reduction of systemic absorption maybe achieved by Lacrimal occlusion following instillation,by closing the eye and applying digital pressure over the lacrimal sac area for about 3 mins . Closing the eye for 3 mins reduces the systemic absorption by 50%

18. Contraindications to Beta-Blockers Asthma and obstructive airway disease Bradycardia CCF 2 nd or 3 rd degree heart block Beta- blockers should not be instilled at bedtime as they cause a profound drop in blood pressure as the individual is asleep , thus reducing optic disc perfusion and potentially causing visual field deterioration.

19. Alpha-2-Agonists They act on alpha- 2- inhibitory receptors located in the ciliary epithelium. Stimulation results in increase in the facility of aqueous outflow - Mechanism of Action:-They decrease IOP by both enhancing aqueous secretion and enhancing uveo scleral outflow. Because the drug crosses the BBB they should not be used in children.

20. Preparations: Brimonidine 0.2% BD in addition to its alpha-2-agonistic action it also has a neuroprotective effect. Apraclonidine 1% is mainly used after laser surgery on the anterior segment to offset an acute rise in IOP. The 0.5% is used shorterm for patient awaiting glaucoma surgery . Not used long term because of tachyphyllaxis .

21. Side-Effects Allergic conjunctivitis Acute granulomatous anterior uveitis Systemic- Xerostomia , drowsiness and fatigue.

22. Follicular Conjunctivitis due to Brimonidine

23. Carbonic anhydrase inhibitors Mechanism of action: They decrease aqueous humor production and are useful for short term therapy in acute cases.

24. Preparations Topical Dorzolamide 2% used TID or BD, has an additive effect with Timolol . Brinzolamide 1% BD or TID ,has lower incidence of stinging and local allergy. Systemic Acetazolamide -the dose is 250-1000mg daily in divided doses with onset of action within 1 hour , peak-4 hours with a duration of upto 12 hours. Dichlorphenamide - The dose is 50mb BID to TID with onset of action within 1 hours, peak-3 hours, with a duration of upto 12 hours. Methazolamide – the dose is 50mb BID to TID with onset of action within 3 hours, peak-6 hours, with a duration of upto 10-18 hours.

25. Side-Effects Parasthesias , numbness lethargy malaise. Metabolic acidosis, hypokalemia , increased serum urate . Urinary Frequency Anorexia, cramps,weight loss flatulence diarrhoea . Sulphonamide related- Renal calculi, blood dyscrasias , Steven Johnson s Syndrome. Topical- allergic blepharoconjunctivitis and bitter taste.

26. Parasympathomimetics Classifiction : Agonists(direct acting)- Pilocarpine Cholinesterase inhibitors (indirect acting):- REVERSIBLE- Physostigmine IRREVERSIBLE- echopthiophate iodide, demacarium Dual action- Carbachol .

27. Mechanism of action POAG- They reduce IOP by , contraction of the ciliary muscle, which increases the facility of aqueous outflow through the trabecular meshwork. Preparations:- Pilocarpine e\d (1%,2%,4%) BID to QID dosage Ocuserts (pilo20, pilo40) Pilocarpine gel 4% HS Carbachol (0.75%,1.5%,3%) BD- TDS dosage maybe useful in pilocarpine sensitivity. Echothiophate iodide (1.25%) OD to BD dosage intense miosis , GI side- effects Demarcarium Bromide (0.125%,0.5%) Physostigmine (0.5%)

28. Side-Effects: Occular - miosis , brow ache,myopic shift, iritis , iris cyst, posterior synechaie , exacerbation of symptoms of cataract and visual field defects appear denser. Systemic- increased salivation, abdominal cramps, diarrhoea , increased sweating , anxiety and bradycardia .

29. Hyperosmotic Agents Mechanism of Action- They lower IOP by creating an osmotic gradient between blood and vitreous so that water is drawn out from the vitreous. Indications- to control acute rise in IOP, prior to intraocular surgery when the IOP is raised.

30. Preparations: Mannitol IV ( 20% solution given 1-2gm/kg over 20 to 30 minutes) cautiously used in hypertensives . Glycerol oral(50% solution 1.5gm/kg to be mixed with equal amount of lime juice or water) cautious use in diabetics. Urea IV not used routinely Isosorbide – metabolically inert.

31. Side-Effects Systemic:- Cardiovascular overload Urinary retention Backache Headache Nausea Confusion Ocular- rebound increase in IOP, aqueous flare.

32. Combined Preparations Combined Preparation with similar ocular hypotensive effects to the sum of the individual components improve convenience and patient compliance. They are also more cost effective. Examples include : Cosopt ( Timolol+Dorzolamide ) b.d Xalacom ( Timolol+Latanoprost ) o.d TimPilo ( Timolol + pilocarpine ) b.d Combigan ( Timolol+Brimonidine ) b.d Ganfort ( Timolol+Bimatoprost ) o.d

33. Frequency of Follow-UP The frequency of follow-up evaluation of a glaucoma patient under active treatment depends upon the IOP level and the stability and severity of the disease . “Stability” refers to the status of IOP, ON, and VF. The higher the IOP or the more severe the glaucoma, the more frequently the patient needs to be evaluated. Every patient diagnosed with glaucoma should be seen at least every 6 months. A dilated-pupil fundus examination and threshold perimetry should be performed at least once per year. The recommended frequencies for follow-up of patients with glaucoma are as follows:  OH and stable mild-stage disease: Every 3-6 months, depending on the duration of IOP control.  Stable moderate-stage disease: Every 2-4 months, depending on the duration of stability and the IOP.  Stable severe disease: Every 1-3 months, depending on the duration of stability and the IOP.  Recently established stability: Every 1-3 months, depending on both the severity of the disease and the IOP.  Unstable disease: Cases in which IOP, ON, or VF is unstable require adjustment of therapy, which could involve weekly or biweekly follow-up for a brief period or until stability is achieved.

34. Surgical approaches for the treatment of POAG Indications Uncontrolled Glaucoma despite maximum medical therapy(3 drugs) and laser trabeculoplasty . Failure of Medical therapy or laser trabeculoplasty . The patient does not tolerate medical therapy. Reactions include allergy, reduced vision due to narrowing of pupil, pain and ciliary spasms. Non-compliance to therapy. Advanced disease requiring low target pressure may benefit from surgery As a primary line of treatment.

35. SURGICAL PROCEDURES TRABECULECTOMY FULL- THICKNESS SCLERECTOMY VISCOCANALOSTOMY Other Procedures-Argon Laser Trabeculoplasty Selective laser Trabeculoplasty Nd -YAG laser Iridotomy Diode laser Cryoablation

36. Argon Laser Trabeculoplasty (ALT) Involves the application of laser burns to the trabecular meshwork and is adjunct to medical therapy. It increases outflow facility by :- 1. Mechanical tightening of the trabecular meshwork to open the adjacent untreated trabecular spaces. 2. It induces cell division and migration of macrophages to clear the trabecular meshwork from debris.

37. Technique 40-50 spots on the anterior half of the trabecular meshwork over 180 degree using a Goniolens . COMPLICATIONS- Acute rise in IOP, Uveitis , hemorrhage , peripheral anterior synechiae .

38. Nd -YAG Laser Iridotomy

39. TRABECULECTOMY It lowers IOP by creating a fistula, to allow aqueous outflow from, the anterior chamber to the sub- tenon’s space. The fistula is protected or guarded by a superficial scleral flap.

40. PROCEDURE Conjunctival Flap Partial thickness scleral Flap Excision of Trabecular tissue Peripheral iridectomy Closure using 10-0 monofilament sutures Subconjunctival injection of dexamethasone and gentamycin

41. Use of Antimetabolites 5- Fluorouracil- Dose is 25-50mg/ml for 2-5 minutes. Mitomycin C- Dose is o.2-0.5mg/ml for 2-5 minutes. Originally advocated for patients with high risk like aphakia , pseudophakia , neovascular glaucoma, H/o failed operations, now also being used routinely by many surgeons.

42. Complications of Trabeculectomy Post-operative shallow AC Hyphaema Iritis Cataract due to accidental injury to the lens Endophthalmitis

43. DRAINAGE SHUNTS Shunts using episcleral explants TYPES:- These create a communication between the anterior chamber and sub- tenon space. All such Shunts consists of a tube attached to a posterior episcleral explant . Some contain pressure sensitive valves for regulation of aqueous flow. Reduction of IOP is due to passive, pressure dependent flow of aqueous across the capsular wall. Molteno , Baerveldt , Ahmed

44. Newer Shunts ExPress Mini Shunt iStent Shunt

45. IMPLANTS

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