Presentation on theme: "Ophthalmic Diseases Ahmed Shaman Clinical Pharmacy Department"— Presentation transcript:
Ophthalmic Diseases Ahmed Shaman Clinical Pharmacy Department
What is glaucoma? Optic neuropathy that is the leading cause of irreversible blindness in the world Major types are open angle and closed angle Glaucoma is commonly associated with elevated intraocular pressure (IOP), but the disease can occur with normal IOP Our understanding and treatment of the disease is very focused on IOP
What is glaucoma? Clear liquid called aqueous humor circulates inside the front portion of the eye To maintain a healthy level of pressure within the eye, a small amount of aqueous humor is produced constantly, while an equal amount flows out of the eye through a microscopic drainage system the trabecular meshwork With glaucoma, aqueous humor does not flow through the trabecular meshwork properly Over time, eye pressure increases, damaging the optic nerve fibers
Effect of Glaucoma
Classification Two main categories of primary glaucoma: Open-angle glaucoma: the most common form of glaucoma Closed-angle glaucoma: a less common and more urgent form of glaucoma
Open-angle glaucoma Trabecular meshwork becomes less efficient at draining aqueous humor Intraocular pressure (IOP) builds up, which leads to damage of the optic nerve Damage to the optic nerve occurs at different eye pressures among different patients. Typically, glaucoma has no symptoms in its early stages
Closed-angle Glaucoma The drainage angle of trabecular meshwork becomes blocked by the iris (the colored part of the eye) IOP builds up very fast Symptoms include severe eye or brow pain, redness of the eye, decreased or blurred vision Must be treated as a medical emergency Without treatment, blindness in as little as one or two days
Open vs. Closed angle Glaucoma
Risk factors for glaucoma include: Age Family history Elevated eye pressure (IOP) Nearsightedness or farsightedness African, Hispanic or Asian ancestry Diabetes Previous eye injury Thin cornea
Glaucoma Management Treatment Options: Medical: Topical systemic medications (PO or IV) Laser: Iridotomy Iridoplasty Trabeculoplasty Surgical: Filtration Surgery (e.g. Trabeculectomy) Tube shunt Destruction of the ciliary body (cyclodestruction)
TREATMENT RATIONALE LOWER IOP BY: (1) Decreasing Production of Aqueous Humor (2) Increasing Outflow of Aqueous Humor
DRUGS THAT DECREASE AQUEOUS PRODUCTION I.Beta-Blockers [levobunolol, timolol, carteolol, betaxolol] -Mechanism: Act on ciliary body to production of aqueous humor -Administration: Topical drops to avoid systemic effects -Side Effects: Cardiovascular (bradycardia, asystole, syncope), bronchoconstriction (avoid with 1- selective betaxolol), depression II.Alpha-2 Adrenergic Agonists [apraclonidine, brimonidine] -Mechanism: production of aqueous humor -Administration: Topical drops -Side Effects: Lethargy, fatigue, dry mouth [apraclonidine is a derivative of clonidine (antihypertensive) which cannot cross BBB to cause systemic hypotension] III.Carbonic Anhydrase Inhibitors [acetazolamide, dorzolamide] -Mechanism: Blocks CAII enzyme production of bicarbonate ions (transported to posterior chamber, carrying osmotic water flow), thus production of aqueous humor -Administration: Oral, topical -Side Effects: malaise, kidney stones, possible (rare) aplastic anemia
DRUGS THAT INCREASE AQUEOUS OUTFLOW I.Nonspecific Adrenergic Agonists [epinephrine, dipivefrin] -Mechanism: uveoscleral outflow of aqueous humor -Administration: Topical drops -Side Effects: Can precipitate acute attack in patients with narrow iris-corneal angle, headaches, cardiovascular arrhythmia, tachycardia II.Parasympathomimetics [pilocarpine, carbachol, echothiophate] -Mechanism: contractile force of ciliary body muscle, outflow via TM -Administration: Topical drops or gel, (slow-release plastic insert) -Side Effects: Headache, induced miopia. Few systemic SE for direct-acting agonists vs. AchE inhibitors (diarrhea, cramps, prolonged paralysis in setting of succinylcholine). III.Prostaglandins [latanoprost] -Mechanism: May uveoscleral outflow by relaxing ciliary body muscle -Administration: Topical drops -Side Effects: Iris color change
TREATMENT: OPEN-ANGLE GLAUCOMA Several large, randomised controlled trials have demonstrated the benefits of early diagnosis and treatment Some controversy exists as to whether the initial therapy of glaucoma should be surgical trabeculectomy (filtering procedure), or selective laser trabeculectomy, or medical therapy Drug therapy remains the most common initial treatment modality Drug therapy of patients with documented glaucomatous change with either elevated or normal IOP is initiated in a stepwise manner
TREATMENT: OPEN-ANGLE GLAUCOMA The goal of therapy is to prevent further visual loss A "target" IOP is chosen based on a patient baseline IOP and the amount of existing visual field loss as well as other risk factors An initial target IOP reduction of 20-30% is desired Greater reductions (30–50%)may be desired for patients with very high baseline IOPs or advanced visual field loss. Patients with normal baseline IOPs (normal-tension glaucoma) may have target IOPs of less than 10 to 12 mm Hg
TREATMENT: OPEN-ANGLE GLAUCOMA Drug choice The prostaglandin (PG) analogues (bimatoprost, latanoprost and travoprost) are replacing beta-blockers as first-line agents. Brimonidine or topical carbonic anhydrase inhibitors (brinzolamide, dorzolamide) tend to be used as alternatives Unless there are contraindications to using beta-blockers or PG analogues Use of pilocarpine is declining, although it may still be useful as adjunctive treatment
Practice Points Up to 50% of patients fail to use their medication correctly One strategy to aid compliance is to use an eye drop containing 2 drugs, eg timolol with a prostaglandin analogue Simple dosage regimens and patient education help compliance To reduce systemic absorption (by up to 70%) close eyes and press on the tear duct for 3 minutes after instillation of each eye drop When >1 type of eye drop is to be instilled at the same time, separate administration by at least 5 minutes
Comparative Information Drug classEffectDoses per day beta-blocker, eg timolol+++1–2 prostaglandin analogue, eg latanoprost+++1 carbonic anhydrase inhibitor, eg dorzolamide++2–3 alpha 2 agonist, eg brimonidine+++2–3 cholinergic (pilocarpine)++2–4
Beta-blockers (eye) Timolol, levobunolol, metipranolol and carteolol are nonselective Betaxolol has β1-selective properties Mode of action Reduce aqueous humour formation, probably by blockade of beta receptors on the ciliary epithelium Indications All types of glaucoma Ocular hypertension Precautions Reversible airways disease, eg asthma—use is generally contraindicated, however cardioselective agents, ie betaxolol, may be used with care.
Beta-blockers (eye) Cardiovascular Consider effects of systemic beta-blockade Use is contraindicated in bradyarrhythmia or second- or third-degree atrioventricular block. Treatment with a systemic beta-blocker reduces intraocular pressure (but less than with a topical beta-blocker). Avoid treatment with verapamil due to potential for profound bradycardia
Beta-blockers (eye) Elderly Systemic adverse effects are more common, e.g. hypotension (may cause falls) Children May cause apnea in neonates and bradycardia in children. Pregnancy May cause fetal bradycardia; Breastfeeding Unlikely to cause adverse effects at usual doses.
Beta-blockers (eye) Adverse effects The most important adverse effects are systemic Common Stinging on instillation (especially betaxolol solution), bradycardia, blurred vision Infrequent decreased corneal sensation, hypotension, syncope, fatigue, confusion, hallucinations, bronchospasm
Beta-blockers (eye) Comparative information Timolol (nonselective beta 1 and beta 2 receptor blocker) Reduces intraocular pressure by 25% when used in 0.25% solution
Beta-blockers (eye) Practice points Slight decrease in effect may occur during the first month of treatment; tolerance may develop after 1 year or more of treatment After stopping topical beta-blockers intraocular pressure may not return to baseline for 2–4 weeks If single daily dosage is required, consider timolol gel or Timoptol-XE ®
Beta-blockers (eye) Dosage – Betaxolol Adult, child, 1 drop twice daily. Dosage – Timolol Use the same way for adults and children. Conventional drops, 1 drop of 0.25% once or twice daily. Maximum 1 drop of 0.5% twice daily. Timoptol-XE ®, 1 drop of 0.25% once daily if necessary, increase to 1 drop of 0.5% once daily. Gel 0.1%, 1 drop once daily Infant <12 months 1 drop of 0.25% (of either formulation) once daily
Beta-blockers (eye) Counselling Gel: store bottle upside down after opening so that gel collects in the bottle neck and stops bubbles forming as it is applied.
Prostaglandin analogues (eye) Ocular Hypotensive Lipids Bimatoprost, latanoprost and travoprost Mode of action Reduce intraocular pressure by increasing uveoscleral outflow of aqueous humour. Indications Glaucoma Ocular hypertension
Prostaglandin analogues (eye) Ocular Hypotensive Lipids Pregnancy Avoid use; no data available; Breastfeeding Unlikely to be of concern; latanoprost is safe to use.
Prostaglandin analogues (eye) Ocular Hypotensive Lipids Adverse effects Common Iris hyperpigmentation, eyelash changes, eye irritation (itching, stinging), allergic conjunctivitis, blurred vision, blepharitis, headache Infrequent Reversible macular oedema, eyelid and conjunctival oedema, darkening of eyelid skin, iritis or uveitis
Prostaglandin analogues (eye) Ocular Hypotensive Lipids Iris hyperpigmentation Gradual (over months to years), usually irreversible, increase in iris pigmentation in treated eyes Eyelash changes Gradual darkening, lengthening and thickening of the eyelashes; reversible when treatment stopped.
Prostaglandin analogues (eye) Ocular Hypotensive Lipids Comparative information Bimatoprost, latanoprost and travoprost appear to have similar efficacy. Counselling These eye drops may slowly change the colour of your eye making the iris appear darker. This change is permanent and may be more noticeable when only one eye is being treated. Practice points Instil in the evening for optimal effect Drugs in this class are structurally different; if response to one is poor, consider trying another a paradoxical increase in intraocular pressure may occur if 2 ocular prostaglandin analogues are used together; avoid combination
Alpha 2 agonists Brimonidine and apraclonidine Mode of action Reduce IOP by suppressing formation and increasing outflow of aqueous humour Indications Chronic open-angle glaucoma Prevention of ocular hypertension following laser surgery Acute closed-angle glaucoma (before laser iridotomy)
Alpha 2 agonists Precautions Severe cardiovascular disease—may worsen; use with caution. Pregnancy Apraclonidine: avoid use; Brimonidine: suitable if necessary; Breastfeeding No data available; unlikely to be a concern.
Alpha 2 agonists Comparative information Apraclonidine Reduce IOP by 25% Effect declines after a month Short-term use (up to 3 months) High incidence of allergic blepharoconjunctivitis with chronic use Brimonidine Reduce IOP by 20% Effective and well tolerated on chronic use
Topical Carbonic anhydrase inhibitors Dorzolamide and brinzolamide Mode of action Inhibit carbonic anhydrase II (predominant subtype found in the eye), which reduces aqueous humour formation Indications Ocular hypertension Open-angle glaucoma
Topical Carbonic anhydrase inhibitors Precautions Allergy to sulfonamides—may increase risk of allergy to carbonic anhydrase inhibitors Pregnancy Avoid use; no human data available; Australian category B3. Breastfeeding No human data available.
Topical Carbonic anhydrase inhibitors Counselling Your eye may feel uncomfortable for a little while after you have put in the drop. If you have blurred vision, avoid driving or operating machinery until your sight improves. Practice points May be used when beta-blocker is ineffective or not tolerated May be used in combination with ophthalmic beta-blockers
Other Drugs for Glaucoma Acetazolamide (Systemic Carbonic Anhydrase Inhibitors) Hyperosmotics Glycerin, isosorbide, and mannitol Cholinergic Agents Pilocarpine and carbachol Nonselective Adrenergic Agonists Epinephrine and its prodrug, dipivefrine
Acetazolamide Systemic carbonic anhydrase inhibitor Mode of action Inhibits carbonic anhydrase and therefore bicarbonate synthesis In the eye this reduces aqueous humour secretion and IOP Indications Perioperative reduction of intraocular pressure, eg acute closed-angle glaucoma Chronic open-angle glaucoma where other treatments have failed
Acetazolamide Precautions Adrenal or respiratory failure or metabolic acidosis—contraindicated (increased risk of profound acidosis). Sodium or potassium depletion—contraindicated (will worsen depletion). Gout—may worsen. Allergy to sulfonamides—may increase risk of allergy to acetazolamide; manufacturer contraindicates use.
Acetazolamide Renal Contraindicated when CrCl <10 mL/minute (increased risk of profound acidosis); reduce dose if CrCl 10–30 mL/minute. Acetazolamide increases risk of recurrence of urolithiasis. Hepatic Contraindicated in hepatic impairment or cirrhosis due to the risk of hepatic encephalopathy. Elderly Increased risk of adverse effects, eg metabolic acidosis.
Acetazolamide Adverse effects Up to 50% of patients do not tolerate acetazolamide. Common paraesthesia (of hands, face, feet or mucocutaneous junctions), fatigue, drowsiness, depression, decreased libido, bitter or metallic taste, nausea, vomiting, abdominal cramps, diarrhoea, black faeces, polyuria, renal stones, metabolic acidosis, electrolyte changes (hypokalaemia, hyponatraemia) Infrequent transient myopia (ciliary body swelling), bullous skin eruptions (Stevens-Johnson syndrome) Rare aplastic anaemia (especially in the first 6 months), thrombocytopenia, agranulocytosis or neutropenia, anaphylaxis
Mannitol Hyperosmotic agent Mode of action Increases plasma osmolality; dehydrates vitreous body. Produces a rapid (30 minutes) but temporary (6 hours) drop in intraocular pressure. Indications Acute closed-angle glaucoma unresponsive to conventional treatment Intraocular pressure reduction before intraocular surgery (prevents prolapse of intraocular contents)
Mannitol Adverse effects Adverse effects are generally infrequent Fluid and/or electrolyte shift can produce pulmonary congestion, acidosis, electrolyte loss, dry mouth, thirst, oedema, headache, blurred vision, seizures and heart failure. Nausea, vomiting, local pain, skin necrosis and thrombophlebitis (injection site), chills, dizziness, urticaria, hypotension, tachycardia, fever, angina-like chest pains Dosage – Mannitol Adult, IV 1–2 g/kg (5–10 mL/kg of 20% solution) over 30 minutes.
Mannitol Administration advice Mannitol crystallises at low temperatures (especially 20% solution); redissolve by warming in hot water and shaking vigorously; allow to cool to body temperature before giving via infusion set with filter. Practice points Mannitol produces a marked osmotic diuresis; urinary catheterisation is required for anaesthetised or unconscious patients The hyperosmotic agent most often used in the treatment of acute ocular hypertension is IV mannitol (oral glycerol is used infrequently)
Cholinergic Agents Pilocarpine and carbachol Mode of action Cholinergic effect contracts Iris sphincter and ciliary muscle Increases outflow through the trabecular meshwork Indications Chronic open-angle glaucoma Acute closed-angle glaucoma
Cholinergic Agents Adverse effects Common blurred vision, headache, ocular irritation (eg burning, itching), myopia, miosis Infrequent lacrimation Rare retinal detachment Headache Accommodative spasm and frontal headache (browache) are common initially usually decrease after 2–4 weeks; simple analgesics may reduce pain Miosis Causes blurred vision, occurs infrequently but is potentially permanent with long-term use and may reduce vision in dim light, worsen the effect of a central visual opacity and constrict the visual field
Nonselective Adrenergic Agonists Dipivefrine Pro-drug, enzymatically cleaved to epinephrine Increase the outflow of aqueous humor through the trabecular meshwork Reduce IOP by 15% to 25% Rarely used now Adverse effects Ocular irritation (include allergic blepharoconjunctivitis) mydriasis, conjunctival hyperemia and frontal headache Not used in patients with narrow angles since these agents can cause acute angle closure
TREATMENT: OCULAR HYPERTENSION Ocular hypertension; i.e., patients with IOP >22 mm Hg [>2.9 kPa] Ocular Hypertensive Treatment Study (OHTS) helped to identify risk factors for treatment Patients with IOPs higher than 25 mm Hg (3.3 kPa) vertical cup-to-disk ratio of more than 0.5 central corneal thickness of less than 555 µm Are at greater risk for developing glaucoma Risk factors such as family history of glaucoma, black ethnicity, severe myopia, and patients with only one eye must also be taken into consideration
TREATMENT: OCULAR HYPERTENSION Patients with significant risk factors usually are treated with a well- tolerated topical agent such as β-blockers Prostaglandin analog a2-Adrenergic Agonist (brimonidine) Topical carbonic anhydrase inhibitor Depending on individual patient characteristics.
TREATMENT: OCULAR HYPERTENSION Optimally, therapy is initiated in one eye to assess efficacy and tolerance Use of second- or third-line agents (e.g., pilocarpine or dipivefrin) when first-line agents fail to reduce IOP depends on the risk-to- benefit assessment of each patient
Acute closed-angle glaucoma This is a rare ophthalmic emergency Treatment is by peripheral laser iridotomy Oral, IV, and topical medication is necessary to stabilise the eye and lower the pressure before laser iridotomy IV acetazolamide, Topical pilocarpine, A topical beta-blocker, IV Mannitol or oral glycerol
Glaucoma surgery Laser iridotomy: creates a small hole in the iris to improve flow of aqueous humor into drainage angle.
Glaucoma surgery Laser trabeculoplasty: stimulates the trabecular meshwork (drainage angle) to function more efficiently
Glaucoma surgery Trabeculectomy: creates new drainage channel for the eye Goal is to stabilize disease and prevent further damage/vision loss Does not reverse damage to the optic nerve Performed on an outpatient basis
Regular Eye Exams Everyone should regularly visit their ophthalmologist at the following intervals: Age years: At least once during this period Those with risk factors for glaucoma (people of African descent or those who have a family history of glaucoma) should be seen every 3-5 years Age years: At least twice during this period Those with risk factors for glaucoma (people of African descent or those who have a family history of glaucoma) should be seen every 2-4 years Age years: Every 2-4 years Age 65 years or older: Every 1-2 years