Medical management of glaucoma

medical management of chronic open angle glaucoma, primary angle closure glaucoma after iridotomy, normotensive glaucoma and acute angle closure attack.

1. MEDICAL MANAGEMENT OF GLAUCOMA Dr Kumar Siddharth

2. PRINCIPLES OF MEDICAL THERAPY Making accurate clinical diagnosis Assessing stage of the disease Assessing risk factors for disease progression Understanding patient’s access to healthcare and socioeconomic factors Considering patient’s lifestyle, health status and life expectancy Implementing treatment strategy on the basis of these factors and other considerations

3. TREATMENT PLAN Goal To manage all patients with glaucoma, preserving visual function while maintaining best possible quality of life Achieving the goal By preventing or slowing the progression of glaucomatous damage by lowering IOP to a level at which further damage is nil or minimal

4. WHEN TO TREAT Elevated IOP, without glaucomatous damage Evaluate risk factors Established glaucomatous damage or dangerously high IOP Treat Treat all if IOP > 28mmHg Treat if IOP < 28mmHG, But elevated Disc suspect (haemorrhage) Retinal vascular occlusion Positive family history Other eye open angle glaucoma Thin CCT < 500 micron Exfoliation OCT defect suspicious of glaucoma Follow up doubtful One eyed patient Angle closure suspect Angle closure

5. APPROACH TO A PATIENT WITH GLAUCOMA NEW PATIENT Chief complaints with medical and ocular history Visual acuity/refraction Tonometry and pachymetry External examination, pupil Slit lamp and gonioscopy Retina, optic nerve head with photo Visual field ESTABLISHED PATIENT Adherence to treatment Tolerance to treatment IOP Stability of optic nerve head and visual function Surgical site, if had surgical intervention

6. Glaucoma- need of medical management Chronic open angle glaucoma Normal tension glaucoma Primary angle closure glaucoma after iridotomy Secondary glaucoma Acute angle closure attack

7. HOW TO START Establishing target IOP Selecting initial medication

8. Target iop Sihota R, angmo D, ramaswamy D, dada T. Simplifying “target” intraocular pressure for different stages of primary open-angle glaucoma and primary angle-closure glaucoma. Indian J ophthalmol 2018;66:495-505 The European Glaucoma Society guidelines define target IOP as “an estimate of the mean IOP obtained with treatment that is expected to prevent further glaucomatous damage” The American Academy of Ophthalmology defines target IOP as “a range of IOP adequate to stop progressive pressure-induced injury” The World Glaucoma Association defines it as “an estimate of the mean IOP at which the risk of decreased vision-related quality of life due to glaucoma exceeds the risk of the treatment.” What is target IOP?? The concept of target IOP: IOP that prevent further progression of glaucomatous visual field loss, without compromising patient’s quality of life.

9. ESTABLISHING TARGET IOP Examination of optic nerve head Intraocular pressure Perimetry Age Additional risk factors

10. 1. Optic nerve Examination of the optic nerve Looking especially at the inferior and superior poles Identify thinning/notching/pallor of the neuroretinal rim retinal nerve fiber layer defects. This provides a measure of the amount of structural damage to the nerve Cup: disc (C: D) ratio is more commonly employed in clinical practice This is best assessed by a 90/78 D examination for accurate delineation of the neuroretinal rim Staging of glaucomatous damage C:D ratio Early <0.65 Moderate 0.7-0.85 Severe >0.9

11. 2. Intraocular pressure At least three IOP measurements Taken at different times of the day Ideally with an applanation tonometer Helps determine baseline IOP, the pressure at which optic nerve damage can be taken to have occurred. Any single IOP measurement taken between 7 am and 9 pm has a > 75% chance of missing the highest point of a diurnal curve. In PACG, it is important that the baseline IOP be recorded after iridotomy. On review, the IOP should be rechecked at the point of peak baseline IOP, if available

12. 3. perimetry Reliable perimetry with reproducible VF defects on at least two consecutive fields Allows staging of the functional visual loss in each patient. Rate of progression on glaucoma progression analysis of Humphrey field analyzer should also be noted, as it will indicate the need of aggression in therapy

13. Grading of glaucomatous damage EARLY MODERATE SEVERE AAO Optic disc cupping but no visual field loss Glaucomatous neuropathy + visual field loss not within 5 degrees of fixation Visual field loss in both hemispheres or within 5 degrees of fixation CNADIAN GUIDELINES C:D ratio <0.65 or Mild visual field defect not within 10 degrees of fixation C:D ratio 0.7-0.85 or Visual field defect not within 10 degrees of fixation or Both C:D ratio > 0.9 or Visual field defect within 10 degrees of fixation or Both INTERNATIONAL CLASSIFICATION OF DISEASES 10 Optic nerve abnormalities consistent with glaucoma + Normal fields Optic nerve anomalies consistent with glaucoma + One hemifield anomaly, not within 5 degrees Optic nerve abnormalities consistent with glaucoma + Both hemifield abnormality or within 5 degrees

14. 4. AGE Collaborative Initial Glaucoma Treatment Study (CIGTS) found that patients who were a decade older had a 40% risk of perimetric loss. Early Manifest Glaucoma Trial (EMGT) reported that those > 68 years old were more likely to progress. On analysis, AGIS also noted that an older patient was more likely to progress. Similar association with age has been seen in PACG eyes as well 

15. 5. Additional risk factors High initial IOP Family history Thin CCT (<500 micron) Exfoliation glaucoma History of PACG attack Steroid use Presence of co morbidities Cardiovascular diseases Sleep apnoea TIA Pseudoexfoliation syndrome

16. Target IOP VALUES

17. B. SELCTING INITIAL MEDICATION The therapeutic goal is to use the least amount of medication that will accomplish the desired therapeutic effect with fewest adverse reactions and affordable for the patients Exceptions for glaucoma therapy with medications include Patients with very high IOP which pose immediate threat to vision History of medical therapy without success or intolerable side effects Problems with adherence to the therapy Angle closure glaucoma Childhood glaucoma

18. Beginning of the therapy– choice of drug Single topical drug Prostaglandin analogues and beta blockers being first choice High compliance Low side effects Low frequency Reasonable cost Systemic drugs can be added initially if IOP is very high (>30mm Hg) at presentation Uniocular trial Reverse uniocular trial If target not achieved with 3 drugs/intolerance – perform surgery

19. Treatment algorithm Prostaglandin analogues Target IOP achieved Target IOP not achieved Well tolerated Not tolerated Continue Switch within group Not tolerated Change group Switch within group Target IOP not achieved IOP fall <15% Change group IOP fall >15% Add drug

20. WHEN TO QUIT AND MOVE ON TO SURGERY Inability to maintain target IOP Progressive glaucomatous damage even on maximum medical therapy Inability of the patient to tolerate or adhere to the medical regimen

21. FOLLOW UP If the IOP is dangerously high or one eyed patient, they should be evaluated within days of the first visit For other cases, it is better to wait for a month or two to get a better sense of long term benefit of the drug After acceptable IOP reduction, revaluated every 3-6 months After years of follow up one may consider to stop the drug in one eye to determine if it is still contributing Patient adherence and general welfare

22. EDUCATING THE PATIENT About the disease Why the medications Treatment will not improve the VA Potential side effects of medication Therapeutic regimen Spacing if more than one drop is being used Administration of eye drops Nasolacrimal occlusion for 5 mins/gentle eyelid closure for 5 mins No frequent blinking movements

23. PHARMACOKINETICS OF TOPICAL DRUGS

24. FORMULATION OF TOPICAL DRUGS

25. PHARMACOGENETICS The study of impact of genetics on drug response is known as pharmacogenetics Predict the disease progression and treatment outcome by studying drug target genes, drug metabolizing enzymes and disease genes Example: One gene variation in Beta 2 adrenergic receptor was associated with 20% greater IOP decrease with use of topical Timolol

26. Factors affecting efficacy of drug Adherence Pharmacokinetics Environmental factors Genetics IOP response Mean IOP before and after treatment Change in IOP Percentage change in IOP Effect on diurnal IOP Drug peak effect on IOP Drug trough effect on IOP Target IOP Contralateral effect Regression to the mean Placebo effect

27. PROSTAGLANDINS AND HYPOTENSIVE LIPIDS Prostaglandins are eicosanoids, metabolic products of arachidonic acid Prostaglandins that reach the systemic circulation are inactivated by lung and liver Small doses (5mcg) lower the IOP

28. Mechanism of action Commercially used prostaglandin analogues are modifications of PGF2alpha which acts on FP receptor Increase in uveoscleral flow by two possible mechanisms: Relaxing the ciliary muscle Matrix metalloproteinase induced remodelling of extracellular matrix of the ciliary muscle (reduction in collagen IV and myocilin) Prostaglandin receptors have 4 subtypes EP, FP, IP, TP FP receptors are G protein coupled receptors with phospholipase C, and inositol phosphate as secondary messenger

29. molecules Name Concentration Frequency LATANOPROST 0.005% Once daily UNOPROSTONE 0.15% Twice daily TRAVOPROST 0.004% Once daily BIMATOPROST 0.03% Once daily TALFUPROST 0.0015% Once daily

30. Features of different molecules Name Features LATANOPROST Latanoprost exhibits thermal and ultraviolet instability Latanoprost unopened bottles should be refrigerated, once opened can be stored at room temperature of up to 25 degrees Celsius for 6 weeks UNOPROSTONE Low efficacy is due to increase in tissue matrix metalloproteinase inhibitors Storage - 2-25 degrees Celsius TRAVOPROST Storage - 2-25 degrees Celsius BIMATOPROST Hydrolysed by cornea to a lesser extent than other analogues Evidence that it also influences trabecular outflow Storage - 15-25 degrees Celsius TAFLUPROST Slightly less efficacious Better tolerated

31. SIDE EFFECTS SIDE EFFECTS PROSTAGLANDIN ANALOGUES Conjunctival hyperaemia [Travoprost >Bimatoprost >Unoprostone>latanoprost] Upregulation of conjunctival fibroblasts Reactivation of herpes simplex keratitis (except Unoprostone) Irreversible pigmentation of iris (stromal) Reversible pigmentation of periocular area Hypertrichosis, stimulating growth phase in the hair cycle Superficial epithelial lesion with long term Allergic contact dermatitis Iris cyst Anterior uveitis and CME has been

32. Drug interaction Additive effect Fixed dose combination Beta blockers Additional IOP reduction Bimatoprost 0.03% + Timolol 0.5%, OD Latanoprost 0.005% + Timolol 0.5%, OD Travoprost 0.004% + timolol 0.5%, OD Alpha agonists Additional IOP reduction Not available Carbonic anhydrase inhibitors (oral/ Additional IOP reduction Not available Cholinergics Additional IOP reduction Not available

33. ADRENERGIC ANTAGONISTS Beta adrenergic receptor antagonists Alpha adrenergic antagonists Not used for long term treatment of glaucoma

34. Mechanism of action of beta blockers Reduces aqueous humour production by acting on beta 2 subtype adrenergic receptor on the ciliary body It causes inhibition of catecholamine induced CAMP in the sympathetic nervous system No effect on outflow Long term use in primates showed degeneration and rarefaction of trabecular meshwork It is not clear whether beta blockers influence the ocular blood flow and its impact on IOP and visual field damage Does not reduce IOP during sleep They do not affect blood aqueous barrier

35. molecules Name Concentration Frequency TIMOLOL MALEATE [Non selective] 0.5% Twice daily Gel form once daily BETAXOLOL HYDROCHLORIDE [Cardio selective] 0.25% Twice daily LEVOBUNOLOL HYDROCHLORIDE [Non selective] 0.5% 0.25% Once daily Twice daily CARTEOLOL HYDROCHLORIDE [Non selective] 1% Twice daily METIPRANOLOL HYDROCHLORIDE [Non selective] 0.3% Twice daily

36. TIMOLOL MALEATE IOP lowering effect on treating and non treating eye via systemic circulation

37. LONG TERM EFFICACY In long term the pressure responsiveness to timolol decreases with continued administration This happens in 2 phases Short term escape Long term drift

38. SHORT TERM DRIFT Dramatic lowering of IOP after initiating the therapy, after which pressure rises to reach a maintenance level The number of beta receptors increase after initiating the therapy Therefore it is prudent to wait for at least a month after initiating the therapy to determine the efficacy

39. LONG TERM DRIFT Some patients show decline in pressure response to timolol, usually after 3 months to 1 year Aqueous production was more in most patients after 1 year of therapy compared to after 1 week of therapy In a study patients were divided in 2 groups after continued timolol therapy In the 30 day timolol holiday period half of them received Dipivefrin and other half tear substitute After the reinstitution of timolol the group that received dipivefrin during the timolol holiday showed mean IOP reduction of 8.2mmHg, compared to IOP reduction of 3.9mmHg in group with tear substitute Based on this observation concept of pulsatile therapy came into the picture

40. FEATURES OF DIFFERENT MOLECULES Betaxolol IOP reduction less than timolol Retinal protection better than timolol Lower plasma level compared to timolol and double the aqueous concentration Levobunolol / Metipranolol IOP reduction and side effects were comparable to timolol Carteolol Intrinsic sympathomimetic action (early transient adrenergic agonist action) Less ocular irritation than timolol IOP reduction comparable to timolol

41. Drug interaction Additive effect Fixed dose combination PG analogues Additional IOP reduction Bimatoprost 0.03% + Timolol 0.5%, OD Latanoprost 0.005% + Timolol 0.5%, OD Travoprost 0.004% + timolol 0.5%, OD Alpha agonists Additional IOP reduction Brimonidine tartrate 0.2% + Timolol 0.5%, BD Carbonic anhydrase inhibitors Additional IOP reduction Timolol more effective with oral CAIs than topical Dorzolamide 2% + timolol 0.5%, BD Brinzolamide 1% + timolol 0.5%, BD Cholinergics Additional IOP reduction Not available

42. OCULAR SIDE EFFECTS Side effects Beta blockers Affects mucous layer of tear film Punctate keratopathy and corneal anaesthesia Cicatricial pemphigoid Betaxolol CME Periocular cutaneous pigmentary changes Metipranolol Granulomatous anterior uveitis

43. Systemic side effects Measurable plasma level is present within 8 minutes or less of topical application

44. Thymoxamine Produces miosis, without shallowing of the anterior chamber or ciliary spasm Role in angle closure glaucoma Miosis without cyclotropia prevents against pigment dispersion Causes substantial narrowing of the palpebral fissure, useful in thyroid ophthalmopathy Reversal of mydriasis Dipiprazole Commercially available for reversal of mydriasis ALPHA ADRENERGIC ANTAGONISTS

45. 3. Adrenergic stimulators Reduce IOP by reducing aqueous production acting on alpha 2 receptors on ciliary epithelium No effect on blood aqueous permeability Increase uveoscleral outflow Apraclonidine Reduce episcleral venous pressure

46. MOLECULES Name Concentration Frequency Apraclonidine hydrochloride [ALPFA 2 AGONIST] 1% 0.5% Thrice daily Brimonidine tartrate [ALPFA 2 AGONIST] 0.2% Thrice daily Dipivefrin and epinephrine [NON SELECTIVE ALPHA AGONIST] 0.1% Twice daily

47. Features of different molecules Apraclonidine Apraclonidine 1% can be used for short term therapy (post laser) Reduces IOP during sleep also Tachyphylaxis Brimonidine Useful to control IOP in post laser Prevents optic nerve head damage, neuroprotective (not confirmed in humans) Dipivefrin Dipivefrin is a modification of epinephrine which makes it lipophilic and increases its penetration 17 folds

48. SIDE EFFECTS Ocular toxicity Ocular side effects Systemic side effects Apraclonidine Follicular conjunctivitis Contact dermatitis Alpha receptor cross reactivity Eyelid retraction Mydriasis Conjunctival blanching Brimonidine Lesser allergic side effects Oral dryness Sedation/ drowsiness/ headache/ fatigue Pronounced CNS depression in children (NOT GIVEN IN LESS THAN 5 YEARS) Dipivefrin Reactive hyperaemia Dark deposits in various ocular structures (adrenochrome) CME (aphakic eyes) Fewer systemic sympathetic side effects compared to epinephrine since it converts to epinephrine after it enters in the eye

49. Drug interactions PG Analogues Additive Not available Beta blockers Additive Brimonidine 0.2% + Timolol 0.5%, BD Carbonic anhydrase inhibitors Additive Brinzolamide 1% + brimonidine 0.2%, TID Pilocarpine Additive Not available

50. 4. Carbonic anhydrase inhibitors Sulphonamide class of drugs Systemic and topical preparations available Decrease aqueous humour flow by inhibition of carbonic anhydrase in ciliary epithelium

51. Mechanism of action In the eye there are 4 variants of carbonic anhydrase The main therapeutic target is the CAII form They alter the ion transport and pH which affect aqueous humour secretion Acetazolamide creates local acidic environment, it inhibits chloride flux across the ciliary epithelium It also creates metabolic acidosis which influences the production of aqueous humour To achieve therapeutic effect 90% of carbonic anhydrase activity needs to be inhibited Increases blood flow velocities in retinal circulation , central retinal and short posterior ciliary arteries but not in ophthalmic artery

52. Molecules Acetazolamide Traditional dose is 250mg QID/ 500mg BD Children 5-10mg/kg body weight every 4-6 hours IV – 250mg stat, followed by 250 mg tabs Tablet - Peak at 2 hrs, lasts 6 hrs Capsule - Peak 8 hrs, lasts 12 hrs Methazolamide 25 mg BD to 100 mg TDS Dorzolamide 2% Thrice daily Brinzolamide 1% Thrice daily

53. Features of different molecules Oral ADDITIVE THERAPY OF TIMOLOL and Acetazolamide Acetazolamide is highly protein bound, needed in higher dose compared to methazolamide Methazolamide Methazolamide Longer half life and lower protein binding Dorzolamide Dorzolamide was most effective and best tolerated in childhood glaucoma Brinzolamide Efficacy same as Dorzolamide

54. Ocular side effects Carbonic anhydrase inhibitors Transient shallowing of AC due to ciliary body oedema, can lead to angle closure Irritation, transient blurred vision occasional hypersensitivity reactions (Dorzolamide>brinzolamide due to lower pH) Periorbital dermatitis Increased mean corneal thickness Potential effect on CAII on corneal endothelium, loss of transparency Dorzolamide Thrombocytopenia Erythema multiforme Bitter taste Brinzolamide Bitter taste

55. Systemic side effects Paraesthesia around fingers, toes and mouth is common Increased urinary frequency Metabolic acidosis Aspirin combined with CAIs can cause salicylate toxicity Potassium depletion (specially combined with other hypokalaemic drugs) Renal calculi Blood dyscrasias (neutropenia, aplastic anaemia)are rare Maculopapular, urticarial type skin eruptions, SJS TERATOGENIC EFFECTS

56. Drug interaction Prostaglandin analogue Additional IOP lowering Not available Beta blockers Additional IOP lowering Dorzolamide 2% + timolol 0.5%, BD Brinzolamide 1% + timolol 0.5%, BD Alpha agonist Additional IOP lowering Brinzolamide 1% + brimonidine 0.2%, TID Cholinergics Additional IOP lowering Not available

57. 5. Cholinergic stimulators Indicated for all forms of open angle glaucoma Stimulate m3 muscarinic cholinergic receptors expressed in human ciliary muscles and iris sphincters (either direct or by acetylcholinesterase action) They lower IOP by increasing facility of aqueous outflow Ciliary muscle contraction which causes traction on scleral spur and alters the configuration of trabecular meshwork and Schlemm canal Minimal stimulation of aqueous humour formation Decreases uveoscleral outflow

58. Molecules Molecules Concentration Frequency Pilocarpine 0.5-4% 4% in high viscosity acrylic vehicle QID OD Bedtime Carbachol 1.5% TDS

59. Features of different molecules Pilocarpine The miotic effect of pilocarpine by action on sphincter pupillae short term management of angle closure glaucoma resulting from pupillary block Carbachol Direct and indirect cholinergic action (blocks acetylcholinesterase enzyme) Poor corneal penetration (needs adjuvant such as benzalkonium chloride) Intracameral carbachol/ acetylcholine for post cataract IOP control Echothiophate iodide Acetylcholinesterase inhibitors Very rarely used Prolonged duration of action

60. Ocular side effects Ciliary muscle spasm, causing browache Transient myopia, axial thickening and forward displacement of the lens (15 mins to 2 hrs after dosing) Retinal detachment suspected, due to vitreoretinal traction Cataractogenic effect has been suggested Corneal haze Increase blood aqueous permeability, increases inflammation, contraindicated in uveitis or anterior segment neovascularisation Cicatricial pemphigoid Hypersensitivity reaction

61. Systemic Side effects Diaphoresis/ increased secretions Nausea vomiting diarrhoea Smooth muscle contraction – bronchospasm, abdominal pain, genitourinary effects Av block Cognitive dysfunctions Antidote – Atropine

62. Drug interaction Additive effects Pilocarpine + timolol Pilocarpine + PGA Pilocarpine + adrenergic agonists Pilocarpine + CAI Fixed dose combinations not available

63. 6. Hyperosmotic agents Reduction in vitreous volume due to change in osmotic gradient between blood and ocular tissues Used as an emergency method of lowering IOP Can be used preoperatively to minimise the pressure effect of the vitreous in supine position

64. Administration Mannitol If crystals are present, it should be warmed to 60-80 degrees and cooled to room temperature before administration Glycerine is safer than mannitol, since it gets metabolised Glycerine Mannitol Dose Orally 1-1.5g/kg body weight (50%solution) IV over 30 mins 1-2 g/kg body weight 25% solution Action Effect peaks at 30 mins, lasts for 5 hours Onset of action is 20-60 mins, duration 2-6 hours

65. Side effects Diuresis, acidaemia, anaphylactic reaction Fluid overload Chills, fever Confusion, stroke Renal insufficiency Increase post operative inflammation Nausea vomiting due to sweet taste, serve with ice and tart flavouring High caloric content can cause dehydration

66. Pregnancy, lactation and children Pregnancy Lactation and paediatric age group Category A (Proven no risk) None Category B (Proven risk in animals, none in humans) Brimonidine Category C (risk in animals but benefit in humans outweigh) Beta blockers Carbonic anhydrase inhibitors Cholinergic agents Prostaglandin analogues Hyperosmotic agents Category D (proven human foetal risk) None Brimonidine Crosses blood brain barriers CNS depression Not given <10 years Cholinergics and adrenergics have systemic side effects and are almost never used in children Oral carbonic anhydrase can cause acidosis and growth retardation with long term use Timolol and dorzolamide are the drug of choice

67. Investigational antiglaucoma drugs Anecortave Angiostatic steroid without glucocorticoid activity Therapeutic potential for ARMD and glaucoma Cannabinoids Smoking marijuana lowers IOP (tetrahydrocannabinol) No effect of topical application in humans Decreases aqueous production Cellular cytoskeletal modulators Ethacrynic acid Changes actin, alpha-actinin, vinculin and vimentin in trabecular meshwork Side effects – corneal and trabecular toxicity Latrunculins Toxins produced by marine sponge Disrupts actin cytoskeleton Cellular signalling pathways Olmesartan (angiotensin II receptor antagonists) Lomerizine (calcium channel blocker) Nivaldipine (calcium channel blocker) Nerve growth factors Memantine NMDA receptor antagonists NMDA receptor excitotoxicity causes inner retinal layer damage Nitric oxide Role in aqueous humour dynamics, blood flow, retinal and optic nerve function Rho kinase inhibitors Rho kinases regulate smooth muscle contractions in calcium independent manner Rho kinase inhibitors increase trabecular outflow

68. RHO KINASE INHIBITORS Rho kinases regulate smooth muscle contractions in calcium independent manner Ripasudil 0.4% twice daily Netrasudil Mechanism Increase trabecular outflow Increases matrix metalloproteinase expression Increase intraocular blood flow

69. Newer modes of treatment Immunomodulation Gene based and cell based treatment Drug delivery Using drainage devices as drug reservoirs Impregnated nasolacrimal plugs

70. Medical management of Secondary glaucoma Aim should be removing the cause of glaucoma. IOP lowering agents can be given Prostaglandin analogues (if no inflammation is present) Beta adrenergic antagonists Alpha analogues Carbonic anhydrase inhibitors Pilocarpine Cycloplegics

71. Medical management of acute angle closure attack Reduction of intraocular pressure IV carbonic anhydrase inhibitors Topical beta blockers Alpha agonists Prostaglandin analogues In difficult cases IV mannitol / Oral Glycerol can be given Miotics Unless the pressure is controlled, miotics will not work because of pressure induced ischaemia of the iris, causing paralysis of ciliary muscle To break the pupillary block 1-3 hours after IOP lowering agent 1%-2% pilocarpine

72. Summary OD - CDR FIELD OF VISION TARGET IOP MILD <0.65 Mild to no visual loss 15-17 MODERATE 0.7-0.85 One hemisphere, not within 10 degrees of central fixation 12-15 SEVERE >0.9 Both hemispheres or within 10 degrees of central fixation 10-12 1. POAG and PACG after iridotomy 2. Ocular hypertension - 18mmHG If IOP>28mmHg If risk factors are present 3. Normal tension glaucoma – IOP fall by 30%

73. summary Prostaglandin analogues Target IOP achieved Target IOP not achieved Well tolerated Not tolerated Continue Switch within group Not tolerated Change group Switch within group Target IOP not achieved IOP fall <15% Change group IOP fall >15% Add drug

74. summary Topical drugs Concentration Frequency Side effects Latanoprost 0.005% OD Conjunctival hyperaemia Pigmentation Inflammation Hypertrichosis Herpes simplex reactivation Travoprost 0.004% OD Bimatoprost 0.03% OD Tafluprost 0.0015% OD Timolol 0.5% BD Systemic adrenergic side effects Mucous layer of tear film Cicatricial pemphigoid Corneal anaesthesia, PEEs Betaxolol 0.25% BD Apraclonidine 1%, 0.5% TID Allergic reaction Oral dryness CNS depression Brimonidine 0.2% TID Dorzolamide 2% TID Corneal endothelial loss Allergic reaction Bitter taste Brinzolamide 1% TID Pilocarpine 0.5% - 4% QID Brow ache Can cause inflammatory reaction Systemic sympathetic side effects

75. Summary Systemic drugs Dose Side effects Acetazolamide Traditional dose is 250mg QID/ 500mg BD Children 5-10mg/kg body weight every 4-6 hours IV – 250mg stat, followed by 250 mg tabs Paraesthesia Potassium depletion Metabolic acidosis Glycerol 1-1.5g/kg body weight Nausea Vomiting Dehydration Mannitol 5 x body weight 20% solution IV over 30 mins Given up to 3 times Acidemia Chills, fever Volume overload Fixed drug combinations Bimatoprost 0.03% + Timolol 0.5% Latanoprost 0.005% + Timolol 0.5% Travoprost 0.004% + Timolol 0.5% Brimonidine 0.2% + Timolol 0.5% Dorzolamide 2% + Timolol 0.5% Brinzolamide 1% + Timolol 0.5% Brinzolamide 1% + Brimonidine 0.2%

76. Thank you