Introduction To Glaucoma Student Slides 2024 PDF

INTRODUCTION TO GLAUCOMA Sarah Larose, BSc Pharm Instructor, Dalhousie College of Pharmacy Wednesday November 22nd 2023 Disclaimer This lecture was prepared for PHAR 1051 in the 2024-2025 academic year. It is as complete and accurate as possible, based on available...

INTRODUCTION TO GLAUCOMA Sarah Larose, BSc Pharm Instructor, Dalhousie College of Pharmacy Wednesday November 22nd 2023 Disclaimer This lecture was prepared for PHAR 1051 in the 2024-2025 academic year. It is as complete and accurate as possible, based on available resources at the time of preparation When read alone, these slides may give the reader an incomplete picture of the presenter’s intended message. The slides are intended to be used in conjunction with the content of Ms. Larose’s verbal lecture to understand the complete intended message. Therefore, please do not copy or reproduce these slides without permission from the author. This lecture is intended to supplement learning from the PBL case. Students are also expected to review content and build on knowledge from anatomy and physiology courses. Learning Objectives By the end of this lecture, students should be able to: Describe and illustrate the anatomy of the eye Explain processes involved in normal regulation of intraocular pressure Compare and contrast open-angle and closed-angle glaucoma (Considering pathophysiology, etiology, risk factors, and clinical presentation) List drugs which may precipitate closed-angle glaucoma Identify the goals of therapy & outcomes in managing open-angle and closed-angle glaucoma Describe management (pharmacological & surgical) of open-angle and closed-angle glaucoma Describe the pharmacologic class, mechanism of action, efficacy, most common and serious adverse effects and precautions of pharmacologic agents used to treat open- angle glaucoma: β-blockers, α-agonists, prostaglandin analogues, carbonic anhydrase inhibitors. ANATOMY REVIEW Anatomy of the Eye Hansen, John T., and Netter, Frank H. Netter's Clinical Anatomy. Third ed. Philadelphia: Saunders, 2014. Chapter 8: Head and Neck. Anatomy of the Eye Avascular The pathophysiology and treatment of glaucoma: a review. JAMA. 2014  Aqueous Humor Purpose: Provides nutrition, removes excretory products, transports neurotransmitters, stabilizes the ocular structure and contributes to regulation of homeostasis of ocular tissues. 3 mechanisms involved in its formation: Diffusion Solutes (esp. lipid soluble) transported proportional to a concentration gradient Ultrafiltration Flow of water + water-soluble substances in response to osmotic gradient Active secretion (80-90%) Selective transcellular movement of anions, cations, and other molecules across a concentration gradient in the blood aqueous barrier 2 passive-flow pathways by which it leaves the eye: Conventional Route (80-85%): via the Trabecular Meshwork to Schlemm’s canal Nonconventional Route: via the ciliary body then out through the sclera (aka. Uveoscleral pathway) Dipiro et al. Pharmacotherapy: A pathophysiologic approach. Chapter 103 Aqueous Humor Dynamics – A Review, 2010. PMID:21293732  Intraocular Pressure (IOP) Created by inflow of aqueous humor from ciliary body and resistance of outflow IOP should result in an inflow rate = outflow rate Median IOP approximately 15.5 +/- 2.5 mmHg IOP impacted by: HR and BP Coughing Neck compression Posture Circadian variation Increased IOP increases risk of optic disk changes and visual field loss Dipiro et al. Pharmacotherapy: A pathophysiologic approach. Chapter 103 Glaucoma “Refers to a variety of conditions with the common feature of an optic neuropathy characterized by a distinctive loss of retinal nerve fibers and optic disc changes” - COS Glaucoma Clinical Practice Guidelines, 2009 It is defined by the neuropathy Other signs “qualify” the diagnosis in relation to the mechanism for the neuropathy Anatomical features: cupping or hemorrhage of the optic disc, RNFL thinning Functional features: visual field changes (normal color vision and acuity*) Important Understanding: ↑ IOP ≠ Glaucoma Optic Disc Changes Image from: http://www.ranelle.com/adult-ophthalmology/glaucoma/ Glaucoma Two main types of glaucoma Open-angle glaucoma Closed-angle or narrow-angle glaucoma Can be: Primary Secondary (to disease, trauma, or drugs) Congenital (structural or functional anomalies that develop prenatally) Primary open-angle glaucoma is more common than closed or narrow-angle glaucoma Accounts for 80-90% Dipiro et al. Pharmacotherapy  Epidemiology Open-angle glaucoma affects approximately 67 million individuals worldwide Approximately 400,000 individuals in Canada 2.7% of Canadians at least 40 years of age and #2 cause of blindness 11% in those 80 years of age and older #1 cause of irreversible blindness Closed-angle glaucoma less common Increased prevalence in older age Dipiro et al. Pharmacotherapy http://www.glaucomaresearch.ca/ COS Canadian Glaucoma Guidelines  Etiology of Primary Glaucoma Open-Angle Glaucoma Closed-Angle Glaucoma Outflow tract is anatomically OPEN Outflow tract is anatomically OBSTRUCTED Increased IOP one factor in May occur as a medical emergency development Mechanical blockage of trabecular Exact cause unknown meshwork Genetic factors & co-morbidities Typically occurs intermittently Optic nerve ischemia Shallow anterior chambers Excitotoxicity Autoimmune reactions Dipiro et al. Pharmacotherapy Pathophysiology The pathophysiology and treatment of glaucoma: a review. JAMA. 2014 Pathophysiology: Closed Angle Glaucoma Physical blockage of trabecular meshwork → blockage of the AH outflow Pupillary block of AH flow from posterior to anterior chamber most common At least 270° of angle is occluded Single or repeated episodes of elevated IOP lead to optic nerve damage Occurs during periods of intermittent blockage “Creeping” angle closure is one type in which the iris adheres to the trabecular meshwork Outflow tract is anatomically OBSTRUCTED The pathophysiology and treatment of glaucoma: a review. JAMA. 2014 Pathophysiology: Open Angle Glaucoma Much less straight forward Pathogenesis is not fully understood Increased resistance to aqueous outflow through the trabecular meshwork Optic nerve damage May occur at normal or elevated IOPs Outflow tract is anatomically OPEN The pathophysiology and treatment of glaucoma: a review. JAMA. 2014 Pathophysiology: Glaucomatous Changes The pathophysiology and treatment of glaucoma: a review. JAMA. 2014  Risk Factors Open-Angle Glaucoma Closed-Angle Glaucoma Elevated IOP Older Age Older Age Female Sex Race/Ethnicity: non-white Race/Ethnicity: East Asian and Chinese (particularly black) race Family history of glaucoma Hyperopia Moderate to high myopia Iris characteristics Thick peripheral iris Low diastolic blood pressure Anterior iris insertion European Glaucoma Society Guidelines for Glaucoma  Clinical Presentation Open-Angle Glaucoma Closed-Angle Glaucoma Typically asymptomatic Acute angle closure Until severe disease Headache, N/V, halos around lights, blurred vision, unilateral eye pain Blind spots and blindness develop Narrow angle at risk of closure Glaucoma Simulator Usually no symptoms except during http://www.glaucomaresearch.ca/ episodes of intermittent closure Creeping/Chronic angle closure Asymptomatic COS Canadian Glaucoma Guidelines Risk Factors: Medications Which may increase IOP in Closed-Angle Glaucoma Anticholinergic agents Topical sympathomimetic agents Antihistamines HOW??? Tricyclic antidepressants (ex. amitriptyline, imipramine) For discussion in PBL Low potency phenothiazines Ipratropium SSRIs, venlafaxine Topiramate Low risk: benzodiazepines, theophylline, vasodilators, systemic sympathomimetics, CNS stimulants, topical cholinergics, MAOIs, carbonic anhydrase inhibitors Dipiro et al. Pharmacotherapy POAG Classification - Severity Medical Management of Glaucoma in the 21st Century from a Canadian Perspective, Journal of Ophthalmology 2016  MANAGEMENT OF OPEN-ANGLE GLAUCOMA Information Sources Tertiary Sources: Textbooks (ex. Dipiro / Pharmacotherapy, A Pathophysiologic Approach) Databases (ex. CPS/RxTx/Therapeutic Choices) Secondary Sources Systematic Review (ex. Cochrane Review) Clinical Practice Guidelines (ex. Canada, US, UK) Primary Sources Studies (ex. OHTS, EMGT, CIGTS) Pharmacy Library Guide https://dal.ca.libguides.com/pharmacy https://dal.ca.libguides.com/pharmacy  Reminder Goals of Therapy Goals need to be made patient specific when presented with a case and include progress and time factors Maintain Quality of Life Reduce IOP (%) Set patient specific IOP goals Resolve/Control Risk Factors Control Hypertension, Diabetes, Physical Activity, etc. Slow progression of disease Progressive Visual Field and Optic Nerve damage CANNOT halt progression Visual Function & Quality of Life Prevent or minimize ADRs of therapy Minimize cost JAMA. Vol 107, Number 3. March 2023 COS Clinical Practice Guidelines Glaucoma, 2009 European Glaucoma Society, Glaucoma Guidelines 2020 Reduce IOP – What is the Target? Suggested IOP Targets from “Guidelines” “Evidence-based clinical practice guidelines for the management of glaucoma in the adult eye” - 2009, Canadian Ophthalmological Society Suggested IOP Targets from “Guidelines” “Primary Open-Angle Glaucoma Preferred Practice Pattern” - 2020, American Academy of Ophthalmology No table, only recommends to target IOP lowering by 25% Or MORE based on severe optic nerve damage, rapid progression or other risk factors Or LESS based on risks of treatment outweighing the benefits Suggested IOP Targets from “Guidelines” “Glaucoma: diagnosis and management NICE Guideline” - 2017, National Institute for Health and Care Excellence No table, recommends “a reduction in IOP of between 25% and 35% from baseline”. Landmark Randomised controlled trials for Glaucoma  Asked the question: Will Topical medication (vs. no treatment) delay/prevent the onset of glaucoma in patients with ocular hypertension? Multicentre, randomized, clinical trial, designed to study the effect of topical medication in delaying or preventing the onset of glaucoma in patients with OHT Treatment goal to lower IOP < 24mm Hg and at least 20% reduction from baseline and followed patients over 5 years These numbers may look familiar. Why? → they are in the Canadian Guidelines IOP Target table!  N:1,636 patients Treatment No Treatment Mean +/- SD reduction in 22.5% +/- 9.9% 4.0% +/- 11.6% IOP Probability of developing 4.4% 9.5% POAG Relative Risk reduction of 50% (p < 0.0001)  Asked the question: Will treatment (vs. no treatment) prevent the progression of glaucoma? Randomized, prospective trial comparing treatment vs. no treatment to evaluate the effectiveness of IOP reduction in early, previously untreated, OAG.  Treatment No Treatment (Laser Trabeculoplasty & Betaxolol) Glaucoma progression, based on visual field, over 5 years 45% 62% A 25% decrease of IOP from baseline reduced the relative risk of progression by 50% Risk of progression was smaller with lower baseline IOP values Risk of progression was smaller with a larger initial IOP drop induced by treatment  Asked the Question: Does the way we lower IOP affect the progression of glaucoma? The CIGTS, a randomized trial, aimed to find out the importance of the means of IOP reduction was examined by comparing intial treatment with medications vs. immediate surgery Target IOP for each patient was individualized using formulas and Medical treatment was escalated in a stepwise manner until target IOP was achieved  Medical Treatment Trabeculectomy Mean IOP 17-18mm Hg (>35% 14-15mm Hg (>45% (post treatment) reduction) reduction) Despite the surgical group achieving lower mean IOP, overall glaucoma field progression rates were the same  Evidence Summary Will topical medication delay/prevent the onset of glaucoma in patients with ocular hypertension? Ie. Patients at RISK of glaucoma (Elevated IOP only – no optic nerve damage) Will treatment prevent the progression of glaucoma? Ie. Patients HAVE glaucoma Does the way we lower IOP affect the progression of glaucoma? Ie. Is surgery better than topical medication? What is Target IOP? The target IOP principle recognizes “lower IOP equals better IOP” and “lower IOP is needed with increasing disease severity” A range from 20% to 40% is used and depends on the extent of damage at presentation and other factors such as age of the patient, family history, life expectancy, etc. 1. At present, the target IOP is estimated and cannot be determined with any certainty in a particular patient. 2. There is no validated algorithm for the determination of a target IOP. This does not, however, negate its use in clinical practice. What is Target IOP? European Glaucoma Society – 2020 Guidelines TREATMENT OPTIONS: PHARMACOLOGICAL  Sites of Medication Activity Aqueous Humour Production: - Beta Blockers - Alpha Agonists - Carbonic Anhydrase Inhibitors Aqueous Humour Outflow: Uveoscleral Outflow: - Prostaglandin Analogues - *Alpha-Agonists Trabecular outflow? The pathophysiology and treatment of glaucoma: a review. JAMA. 2014  Important Guidance Justification ≠ “It is a 1st line treatment” Justification = the reasons WHY it is a 1st line treatment for this patient  What is “First Line” Treatment? European Glaucoma Society, Glaucoma Guidelines 2020 Topical IOP-lowering medications Latanoprostene 2017 ? 2019 Netarsudil (not yet in Canada) Medical Management of Glaucoma in the 21st Century from a Canadian Perspective, Journal of Ophthalmology 2016  Available Options Grouped by Class α2-adrenergic agonists Apraclonidine, Brimonidine β-adrenergic antagonists Betaxolol, Timolol Carbonic anhydrase inhibitors Brinzolamide, Dorzolamide Prostaglandin analogue Bimatoprost, Latanoprost, Latanoprostene*, Travoprost Parasympathomimetic agents Pilocarpine RxFiles: Glaucoma Drug Comparison Chart JAMA. Vol 107, Number 3. March 2023 COS Clinical Practice Guidelines Glaucoma, 2009  Mechanism of Action General impact on IOP via aqueous humor α2-adrenergic agonists Decrease aqueous humor production & increase outflow** β-adrenergic antagonists Decrease aqueous humor production Carbonic anhydrase inhibitors Decrease aqueous humor production Prostaglandin analogue Increase uveoscleral outflow of aqueous humor Parasympathomimetic agents Increase aqueous humor outflow RxFiles: Glaucoma Drug Comparison Chart JAMA. Vol 107, Number 3. March 2023 COS Clinical Practice Guidelines Glaucoma, 2009  Efficacy Approximate expected reduction in intra-ocular pressure α2-adrenergic agonists 20-25% β-adrenergic antagonists 20-25% Carbonic anhydrase inhibitors 15-20% Prostaglandin analogue 25-35% Parasympathomimetic agents 20-30% RxFiles: Glaucoma Drug Comparison Chart JAMA. Vol 107, Number 3. March 2023 COS Clinical Practice Guidelines Glaucoma, 2009  Safety Contraindications/Precautions and Drug Interactions Fatigue, drowsiness, hypotension α2-adrenergic agonists Sedatives; hydrocodone, MAOIs Severe asthma, COPD, bradycardia, heart block, heart failure; β-adrenergic antagonists High doses of systemic β-blockers, digoxin, quinidine, non-DHP CCB Sickle cell disease; Carbonic anhydrase inhibitors Use caution in patients with sulfa allergy Active uveitis; Prostaglandin analogue No interactions reported Ocular inflammation; Parasympathomimetic agents Dicyclomine RxFiles: Glaucoma Drug Comparison Chart JAMA. Vol 107, Number 3. March 2023 COS Clinical Practice Guidelines Glaucoma, 2009  Safety Adverse Drug Reactions - LOCAL α2-adrenergic agonists Allergy (esp. apraclonidine – 50%), burning, stinging β-adrenergic antagonists Best tolerated. Burning, stinging Carbonic anhydrase inhibitors Burning, stinging, bitter taste, punctate keratitis Hyperemia, burning, stinging, itching, foreign body sensation, eye Prostaglandin analogue pain, iris pigmentation, eyelash lengthening, photophobia Rare: anterior uveitis, cystoid macular edema Miosis with refractive changes, burning, stinging, headache, Parasympathomimetic agents cataracts; paradoxical angle closure RxFiles: Glaucoma Drug Comparison Chart JAMA. Vol 107, Number 3. March 2023 COS Clinical Practice Guidelines Glaucoma, 2009  Safety Adverse Drug Reactions - SYSTEMIC α2-adrenergic agonists Dry mouth/nose, ↓HR, ↓BP, somnolence, fatigue Cardiopulmonary (exacerbate obstructive pulmonary conditions, β-adrenergic antagonists ↓HR, ↓BP) hallucinations, fatigue, malaise; mask hypoglycemia Carbonic anhydrase inhibitors Bitter taste. Few, if any, systemic adverse effects Skin reaction, URTI. Prostaglandin analogue Rare: dyspnea, asthma Rare cholinergic adverse effects; increased salivation; headache; Parasympathomimetic agents tremor, ↓BP/HR RxFiles: Glaucoma Drug Comparison Chart JAMA. Vol 107, Number 3. March 2023 COS Clinical Practice Guidelines Glaucoma, 2009  Dosing Frequency Relevant for convenience / adherence α2-adrenergic agonists BID-TID (duration of effect is 8-12 hours) β-adrenergic antagonists BID (unless XE product = once daily) Carbonic anhydrase inhibitors BID (combination therapy) – TID (monotherapy) Prostaglandin analogue qHS Parasympathomimetic agents TID - QID RxFiles: Glaucoma Drug Comparison Chart JAMA. Vol 107, Number 3. March 2023 COS Clinical Practice Guidelines Glaucoma, 2009 Treatment Algorithm(s) CPS, Therapeutic Choices Chapter: Glaucoma  Special Considerations of a Pharmacist Adherence Unable/Difficult to detect non-adherence, unless VOLUNTEERED by patients Questions to consider asking: “Have you forgotten to use your eye drops in the last week? If yes how many times? “Does anyone help you administer your drops?” “Can you show me how you put your drops in?” Common Obstacles: Medication: cost, ADR, complicated regimen Individual: situational/environmental, forgetfulness, poor understanding disease, gender, stage of disease Clinician: lack of communication Pregnancy & Breastfeeding Balance the potential risks to the fetus (and neonate) against the risk of vision loss in the mother IOP levels may decrease during pregnancy temporarily, temporary treatment discontinuation MAY be considered Use techniques to reduce systemic absorption: Punctal occlusion and eyelid closure None are labelled for “Use in Pregnancy” – Why might that be? CPS, Therapeutic Choices Chapter: Glaucoma Pregnancy & Breastfeeding  MANAGEMENT OF CLOSED-ANGLE GLAUCOMA Goals of Therapy Reminder Goals need to be made patient specific when presented with a Resolve patient specific signs and symptoms case and include progress and time factors Reduce IOP Set patient specific IOP goals Slow progression of disease Maintain visual field Prevent Blindness, Prevent damage to the optic disk, Improve quality of life Prevent or minimize AEs of therapy Prevent Recurrence/Lengthen Symptom Free Interval Minimize cost Maintain QoL CPS, Therapeutic Choices Chapter: Glaucoma COS Clinical Practice Guidelines Glaucoma, 2009 Overview Consider stage and severity of disease Remove underlying causes Laser or surgical interventions first line for management of closed-angle glaucoma Ongoing elevations in IOP post-procedure may warrant initiation of pharmacologic therapy similar to management of open angle glaucoma Weinred RN et al. Pathophysiology and Treatment of Glaucoma: A Review. Nonpharmacologic Treatment Laser and surgical procedures Laser iridotomy: hole in iris to permit flow of aqueous humor from posterior to anterior chamber Iridectomy: removal of part of the iris ↑ OUTflow Typically used for cases refractory to iridotomy Drainage tube insertion: Tube inserted into anterior chamber to permit drainage of aqueous humor Refractory cases Laser ciliary body ablation ↓ INflow Advanced glaucomas CPS, Therapeutic Choices Chapter: Glaucoma  Laser Iridotomy Image from: Weinreb RN, Aung T, Medeiros FA. The Pathophysiology and Treatment of Glaucoma: A Review. JAMA 2014;311(18):1901-11.  Pharmacologic Adjunct Treatment Reduce Reduce IOP Re-open the angle Inflammation Reduce/Block AH Production Pupillary Constriction Anti-inflammatory Topical Therapy (also reduces iris thickness and Topical therapy α-agonists or β-blockers facilitates perforation) Corticosteroids Topical therapy Pilocarpine Systemic Therapy Carbonic anhydrase inhibitor (Acetazolamide) Dehydrate the Vitreous Body Hyperosmotics Oral: glycerol IV: manitol European Glaucoma Society Acute Closed-Angle Glaucoma Tx Summary EMERGENCY requiring IMMEDIATE treatment Institute agents to lower IOP (ophthalmic and systemic) while awaiting laser/surgical intervention Laser iridotomy (first line) and successful in 42-72% of attacks Many patients recover without optic disc or visual field damage if the pressure is promptly and adequately controlled. Weinred RN et al. Pathophysiology and Treatment of Glaucoma: A Review. Closed-Angle Glaucoma Narrow angle with normal IOP Moderate to high risk of angle closure attack suggest laser iridotomy Chronic angle closure After iridotomy is completed, achieve control of IOP as per open angle glaucoma SOC Glaucoma Clinical Practice Guidelines, 2009  Role of the Pharmacist Recognize risk factors, including medications, that put a patient at higher risk for experiencing ACAG Recognize signs & symptoms of ACAG and refer appropriately State the medications used to treat ACAG and describe their purpose Select References & Resources Canadian Glaucoma Guidelines: Canadian Ophthalmological Society Evidence-Based Clinical Practice Guidelines for the Management of Glaucoma in the Adult Eye. Canadian Journal of Ophthalmology 2009;44(Suppl 1) European Guidelines European Glaucoma Society Terminology and Guidelines for Glaucoma, 5th Edition. Br J Ophthalmol. 2021 Jun;105(Suppl 1):1-169. Dipiro et al. Pharmacotherapy: A Pathophysiologic Approach Therapeutic Choices, CPhA (CPS) Glaucoma: Diagnosis and Management. American Family Physician. Volume 107, Number 3. March 2023.