Open-angle glaucoma

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Rohan Bir Singh, M.B.B.S.[2]

Historical Perspective

Glaucoma has been known in medicine since Antiquity. In Greek 'glaukos' a word appearing in the works of Homer where it seems to mean a sparkling silver glare. Later the word was used for colours such as sky-blue or green.The word entered ophthalmology when Hippocrates, in his “Aphorisms”, lists among the infirmities of the aged a condition he called “glaucosis” which he associated with “dimness of vision”. The implied meaning is that of a clouded or blue-green hue of the cornea in end stage forms that may result in corneal edema and/or coinciding cataract. The Hippocratic writings make no clear distinction between cataract and glaucoma. Both Classical and Alexandrian Greeks did not recognize the specific disease which we now call glaucoma.

The definition of glaucoma has changed drastically since its introduction around the time of Hippocrates in approximately 400 BC. The first recognition of a disease associated with a rise in intraocular pressure and thus corresponding to what is now known as glaucoma occurred in the Arabian writings, “Book of Hippocratic treatment”, of At-Tabari (10th century). In European writings, it was Richard Bannister (1622), an English oculist and author of the first book of ophthalmology in English, who recognized glaucoma as a disease with four features: increased intraocular pressure, long duration of the disease, the absence of perception of light and the presence of a fixed pupil. However, throughout the 18th century the term glaucoma was still merely a label applied to an inflamed eye wherein the pupil appeared greenish-blue and the visual prognosis was bad, but the tension of the eye was not stressed.

It was only after the careful description by Antoine-Pierre Demours (1818) that the central concept of a rise in intraocular pressure became fully established. G.J. Guthrie (1823) and William McKenzie, a Scottish clinician (1835) confirmed these findings. Donders (1862) described an incapacitating increased eye tension occurring without any inflammatory symptoms as "simple glaucoma". In 1973 Drance provided for the first time the definition of glaucoma as an optic neuropathy caused by increased intraocular pressure and other associated risk factors.

The first patient in the United States federal government's Compassionate Investigational New Drug program, Robert Randall, was afflicted with glaucoma and had successfully fought charges of marijuana cultivation because it was deemed a medical necessity (U.S. v. Randall) in 1976.

Classification

Open-angle Glaucoma
Primary open-angle glaucoma (POAG) (H40.11)	not associated with known ocular or systemic disorders that cause increased resistance to aqueous outflow or damage to optic nerve usually associated with elevated IOP
Normal-tension glaucoma (H40.12)	considered in continuum of POAG; often used when IOP is not elevated
Juvenile open-angle glaucoma	used when open-angle glaucoma diagnosed at young age (typically 10-30 years of age)
Glaucoma suspect (H40.0)	normal optic disc and visual field associated with elevated IOP suspicious optic disc and/or visual field with normal IOP
Secondary open-angle glaucoma	increased resistance to trabecular meshwork outflow associated with other conditions (e.g. pigmentary-, phacolytic-, steroid-induced-) increased posttrabecular resistance to outflow secondary to elevated episcleral venous pressure (e.g. carotid cavernous sinus fistula)

Epidemiology and Demographics

Primary open-angle glaucoma (POAG) poses a significant public health problem. The estimated prevalence of POAG in the United States in individuals older than 40 years is 1.86% (95% confidence interval, 1.75%–1.96%), based on a meta-analysis of population-based studies. Applied to data from the 2000 US census, this percentage translates to nearly 2.22 million Americans affected. The number of POAG patients is estimated to increase by 50%, to 3.36 million in 2020.

The World Health Organization (WHO) undertook an analysis of the literature to estimate the prevalence, incidence, and severity of the different types of glaucoma on a worldwide basis. The data collected predominantly in the late 1980s and early 1990s, it was estimated the global population of persons with high IOP (>21 mm Hg) to be 104.5 million. The incidence of POAG was estimated at 2.4 million persons per year. Blindness prevalence for all types of glaucoma was estimated at more than 8 million persons, with 4 million cases caused by POAG. Glaucoma was theoretically calculated to be responsible for 12.3% of blindness. This makes glaucoma the second leading cause of blindness worldwide, following cataract.

The estimated prevalence varies widely as per different studies population-based samples; the Rotterdam Study (northern European population) showing a prevalence of 0.8% and the Barbados Eye Study (Caribbean population) showing a prevalence of 7% in individuals older than 40 years. In these studies, there is an increase in the prevalence of glaucoma in older individuals, with estimates for persons in the 7th decade being generally 3 to 8 times higher than those for persons in their 4th decade.

Among whites aged 40 years and older, a prevalence of between 1.1% and 2.1% has been reported based on population-based studies performed throughout the world. The prevalence among black persons and Latino persons is up to 4 times higher compared to the prevalence among whites. Black individuals are also at greater risk of blindness from POAG, and this risk increases with age: in persons aged 46–65 years, the likelihood of blindness from POAG is 15 times higher among blacks than that among whites.

Risk Factors

• Age : The risk increases with the increase in age.The visual field defects were 7 times more likely to progress in patients aged 60 years or older than in those younger than 40 years. Although increased lOP with age has been observed in many populations and may account for part of the relationship between age and glaucoma, studies in Japan have shown a relationship between glaucoma and age even with no increase in lOP in the population.
• Race : The prevalence of POAG is 3 to 4 times greater in black persons and Hispanic persons than in non-Hispanic white individuals. Blindness from glaucoma is at least 4 times more common in blacks than in whites. Glaucoma is more likely to be diagnosed at a younger age and likely to be at a more advanced stage at the time of diagnosis in black patients than in white patients.The Baltimore Eye Survey found that the prevalence of glaucoma increases dramatically with age, particularly among black persons, exceeding 11% in those aged 80 years or older.
• Family History: A positive family history is also a risk factor for POAG. The relative risk of POAG is increased approximately 3.7-fold for individuals who have a sibling with POAG.
• Myopia : The evidence supports an association between POAG and myopia. The concurrence of POAG and myopia cause difficulty in diagnosis and management of POAG. There is an increased difficulty in evaluation of the optic disc is particularly complicated in highly myopic eyes that have tilted discs or posterior Staphyloma. The magnification of the disc due to the myopic refractive error interferes with optic disc evaluation. Myopia-related retinal abnormalities can cause visual field defects apart along with glaucoma. High refractive error may also make it difficult to perform accurate perimetric measurement and to interpret visual field abnormalities.
• Diabetes Mellitus : The role of diabetes mellitus in causing POAG is still controversial. Though some studies have found diabetes plays a significant role in the disease, other studies have not found diabetes to be major risk factor.
• Hypertension : The systemic hypertension is associated with a low risk of the presence of glaucoma in younger patients and with an increased risk in older (>65 years) patients. It is considered that with advancing age, the adverse effects of chronic hypertension on the optic nerve microcirculation may lead to the nerve's susceptibility to the development of glaucomatous optic neuropathy. Many studies demonstrate that lower ocular perfusion pressure is a strong risk factor for the development of glaucoma, independent of lOP alone. Some research groups define ocular perfusion pressure as blood pressure (systolic, diastolic, or mean arterial) minus lOP. The overtreatment of systemic hypertension may be a contributing factor to glaucoma progression in some cases and hence, should be avoided.
• Retinal vein occlusion : The patients with central retinal vein occlusion may lead to an elevated lOP and glaucoma. In some case, there may be presentation of preexisting POAG or other types of glaucoma. After CRVO, patients may develop angle-closure glaucoma or, at a later stage, neovascular glaucoma. The comorbidity is due to elevated lOP in susceptible individuals, thus are at risk of developing CRVO.
• Sleep apnea
• Thyroid disorders
• Hypercholesterolemia
• Migraine
• Raynaud Phenomenon

Diagnosis

History and Symptoms | Physical Examination | Laboratory Findings | Electrocardiogram | Chest X Ray | CT | MRI | Echocardiography or Ultrasound | Other Imaging Findings | Other Diagnostic Studies

Treatment

Medical Therapy | Surgery |

Medical Management of Glaucoma

1. Two decisions arise in choosing an appropriate glaucoma therapy:

   • when to treat
   • how to treat

2. Primary angle-closure and infantile glaucoma are treated as soon as the diagnosis is made.
3. Open-angle glaucoma is treated:

   • when damage to the optic nerve has been demonstrated in the form of progressive pathologic cupping and/or characteristic visual field defects
   • when IOP is elevated to an extent that it is likely to cause damage to the optic nerve.

4. The goal of currently available glaucoma therapy

   • To preserve visual function by lowering IOP below a level that is likely to produce further damage to the nerve.
   • The treatment regimen should have lowest risk, fewest side effects, and least disruption of the patient’s life

5. Target pressure goal

   • Should actually be a range with an upper IOP limit that is unlikely to lead to further damage of the nerve in a given patient
   • The more advanced the glaucomatous process on initial presentation, the lower the target pressure generally needs to be prevent further progression.
   • An initial reduction in the IOP of 20%-30% from baseline is suggested, but those patients who have progressive NTG may require a decrease of at least 30% from baseline.
   • The target pressure range needs to be reassessed or changed as comparisons of IOP fluctuations, optic nerve changes, and/or visual field progression dictate.

6. The anticipated benefits of any therapeutic regimen should justify the risks, and regimens associated with substantial side effects should be reserved for patients with a high probability of eventual severe visual dysfunction.

Drugs

• Ocular hypotensive agents are divided into several group based on chemical structure & pharmacologic action:

1. Beta-adrenergic antagonists (nonselective and selective)
2. Parasympathomimetic(miotic)agents,including cholinergic and anticholinesterase agents
3. Carbonic anhydrase inhibitors (oral, topical)
4. Adrenergic agonists (nonselective and selective alpha2 agonists)
5. Prostaglandin analogues
6. Combination medications
7. Hyperosmotic agents

1. Beta Adrenergic Agonists (Beta Blockers)

   • Mechanism of action of topical beta blockers
     • Inhibition of cAMP production in ciliary epithelium → reduction of aqueous humor secretion 20%-50% (2.5 ml/min to 1.9 ml/min) → IOP reduction of 20%-30%.
   • The effect of beta blockers on aqueous production occurs within 1 hour of instillation and can be present for up to 4 weeks after discontinuation.
   • As systemic absorption occurs, a contralateral effect with lowering of the IOP in the unilateral eye can also be observed.
   • Beta blockers are additive in combination with miotics, adrenergic agonists, CAIs (oral, topical) and prostaglandin analogues.
   • Approximately 10%-20% of the patients treated with topical beta blockers fail to respond with significant lowering of the IOP.
   • If a patient is on systemic beta-blocker therapy, the addition of topical beta blockers may be significantly less effective.
   • Use of beta blockers for more than months to years may reduce their effectiveness, as the response of beta receptors is affected by constant exposure to an agonist (long-term drift, tachyphylaxis). Similarly, receptor saturation (drug-induced upregulation of beta receptors) may occur within a few weeks, with loss of effectiveness (short-term escape)
   • Six topical beta blockers are approved for use for the treatment of glaucoma in the US. All except betaxolol are non cardioselective beta1 and beta2 antagonists. Beta1 activity is largely cardiac and beta2 activity largely pulmonary.
     • Betaxolol (0.25%, bid)
     • Carteolol hydrochloride (1.0%, qd, bid)
     • Levobunolol ( 0.25%, 0.5%, qd, bid)
     • Metipranolol (0.3%, bid)
     • Timolol maleate (0.25%, 0.5%. qd, bid)
     • Timolol hemihydrate (5.12 mg/ml, qd, bid)
   • Since betaxolol is a selective beta1 antagonist, it is significantly safer than the nonselective beta blockers when pulmonary, CNS, or other systemic conditions are considered. Betaxolol may be useful in patients with a history of bronchospastic disorders, although other therapies should be tried in lieu of betaxolol, as beta selectivity is only relative and not absolute, and some beta2 effect can therefore remain. In general, the IOP-lowering effect of betaxolol is less than the nonselective beta blockers.
   • Carteolol demonstrates intrinsic sympathomimetic activity, which means that, while acting as a competitive antagonist, it also causes a slight to moderate activation of receptors. Thus, even though carteolol produces beta-blocking effects, these may be tempered, reducing the effect on cardiovascular and respiratory systems. Carteolol may also be less likely to adversely affect the systemic lipid profile when compared with other beta blockers.
   • Ocular and systemic side effects
     • bronchospasm
     • bradycardia
     • increased heart block
     • lowered blood pressure
     • reduced exercise tolerance
     • CNS depression
     • Diabetic patients may experience reduced glucose tolerance and masking of hypoglycemic signs and symptoms.
     • Abrupt withdrawal of ocular beta blockers can exacerbate symptoms of hyperthyroidism.
     • Other side effects include lethargy, mood changes, depression, altered mentation, light-headedness, syncope, visual disturbance, corneal anesthesia, punctate keratitis, impotence, reduced libido, allergy and alteration of serum lipids.

2. Parasympathomimetic agents

   • Classification
     • Direct-acting cholinergic agonists (e.g., pilocarpine)
       • Affect the motor end plates in the same way as acetylcholine, which is transmitted at postganglionic parasympathetic junctions, as well as at other autonomic, somatic, and central synapses.
     • Indirect-acting anticholinesterase agents (e.g., echothiophate iodide,demecarium bromide)
       • Inhibit the enzyme acetylcholinesterase, thereby prolonging and enhancing the action of naturally secreted acetylcholine.
   • Carbachol has both direct and indirect actions, although its primary mechanism is direct.
   • Mechanism of IOP Reduction
     • both direct- and indirect-acting agents Contraction of the ciliary muscle, which pulls the scleral spur to tighten the trabecular meshwork, increasing the outflow of aqueous humor.
   • These agents can reduce the IOP by 10%-20%.
   • The currently accepted indications for miotic therapy
     • Chronic treatment of increased IOP in patient with at least some filtering angle
     • Prophylaxis for ACG prior to iridectomy
   • Other actions of the parasympathomimetic agents
     • Reduce uveoscleral outflow. This action may actually worsen the glaucoma if miotics are used in patients with little to no trabecular outflow.
     • Cause the pupillary sphincter to contract, stimulate secretory activity in the lacrimal and salivary glands, and disrupt the blood-aqueous barrier. These actions have little bearing on the IOP-lowering effect, except in ACG, where the mechanical action of the contracting pupillary sphincter may pull the iris away from the trabecular meshwork.
   • Side effects of miotic agents
     • Retinal detachment, especially in patients with peripheral retinal disease.
     • Induced myopia, brow ache, alteration of vision in dim light and in patients with lens opacities.
     • Paradoxical angle closure (indirect-acting miotics or the stronger direct- acting agents), caused by the contraction of ciliary muscle leads to forward movement of the lens-iris diaphragm, an increase in the anteroposterior diameter of the lens, and a very miotic pupil. The concomitant administration of an alpha-adrenergic agonist such as phenylephrine may cause a larger pupil without interfering with the reduction of IOP.
     • Generalized cataract formation in addition to anterior subcapsular opacity (indirect-acting miotics). Direct-acting agents may also be weakly cataractogenic.
     • Formation of iris pigment epithelial cysts (indirect-acting miotics)
     • Ocular surface changes (pseudopemphigoid) (indirect-acting miotics)
     • Increased inflammation following surgery (stronger miotics) : Anti- cholinesterase agents should be discontinued and other agents substituted at least 2-4 weeks prior toocular surgery, because they cause significant bleeding during surgery and severe fibrinous iridocyclitis postoperatively.
     • Breakdown of the blood-aqueous barrier. Thus, their use in treating uveitic glaucoma should be limited.
     • Systemic parasympathetic stimulation such as diarrhea, abdominal cramps, increased salivation, bronchospasm and enuresis (indirect-acting miotics). Since cholinesterase is suppressed throughout the body, depolarization agents such as succinylcholine should be avoided while the patient is using these eyedrops and for 6 weeks after discontinuation.
   • Preparations
     • Pilocarpine HCl 0.2%, 0.5%, 1.0%, 2.0%, 3.0%, 4.0%, 6.0%, bid-qid
     • Pilocarpine nitrate 1.0% - 4.0%, bid-qid
     • Pilocarpine membrane 20ug, 40ug, q5-7d → releases drug at a steady rate for approximately 1 week; the induced myopia is more stable and the miosis is less marked than with eyedrop therapy; the release of drug and the induced symptoms are greatest during the first 24 hours; tolerated better when administered at bedtime.
     • Pilocarpine gel 4.0% qhs,it may lead to loss of drug effect after 18-20 hours; induced myopia and miosis are less prominent than with drops.
     • Carbachol 1.5%, 3.0%, bid, tid
     • Echothiophate iodide 0.03%, 0.06%, 0.125%, 0.25%, qd, bid
     • Physostigmine 0.25%, 0.5%, qd, bid
     • Demecarium bromide 0.125%, 0.25%, qd, bid
     • Pilocarpine membrane and pilocarpine gel may be useful:
       • In some younger patients.
       • In patients bothered by variable myopia or intense miosis.
       • In older patients with lens opacities.
       • In patients who have difficulty complying with more frequent dosing regimen
     • Indirect-acting agents are usually reserved for treatment of glaucoma:
       • In aphakic and pseudophakic eyes when IOP is not controlled by less toxic agents
       • In phakic eyes when filtering surgery has failed.

3. Carbonic Anhydrase Inhibitors
   • Mechanism of action

   • Direct antagonist activity upon ciliary epithelial carbonic anhydrase, producing a generalized acidosis.
   • The enzyme carbonic anhydrase is also present in many other tissues, including corneal endothelium, iris, retinal pigment epithelium, brain and kidney.
   • Over 90% of the ciliary epithelial enzyme activity must be abolished to decrease aqueous production and lower IOP.
   • Systemic Agents
     • Most useful in acute situations (e.g., acute ACG). Can be given orally, intramuscularly, and intravenously.
     • Because of the side effects of the systemic CAIs, chronic therapy with these agents should be reserved for patients whose glaucoma cannot be controlled by alternative topical therapy.
     • The oral agents most commonly used are acetazolamide and methazolamide. The lowest dose that reduces the IOP to an acceptable range should be used. Methazolamide has longer duration of action; less bound to serum protein; metabolized by liver, thereby decreasing the risk of systemic side effects; 25-50 mg 2-3 times daily. Acetazolamide is not metabolized; excreted in urine; may be started at 62.5mg every 6 hours, and higher doses may be used if tolerated.
     • Side effects
       • paresthesias of the fingers or toes, lassitude, loss of energy, anorexia, weight loss, abdominal discomfort, diarrhea, loss of libido, impotence, unpleasant taste in the mouth, several mental depression, increased risk in formation of calcium oxylate and calcium phosphate renal stones, allergic reactions (sulfa derivatives), cross reactivity, hypokalemia, aplastic anemia, thrombocytopenia, agranulocytosis.
   • Preparations:
     • acetazolamide 62,5mg, 125mg, 250mg, 500mg, bid-qid (oral)
     • acetazolamide 500mg (parenteral) 5-10mg/kg, usually ≤ 1qd q6-8hrs
     • methazolamide 25mg, 50mg, 100mg, bid, tid
     • dichlorphenamide 50mg, bid, tid
   • Topical Agents
     • Dorzolamide and brinzolamide are topical CAI agents available for chronic treatment of IOP elevation. They reduce IOP (monotherapy) by 14%-17%.
     • Side effects
       • bitter taste, blurred vision, punctate keratopathy, and systemic lassitude. Ocular surface irritation with dorzolamide may be a result of the relative greater acidity (lower pH)when compared with brinzolamide. The brinzolamide solution may cause more blurring than the dorzolamide solution.
   • Preparations:
     • dorzolamide 2.0%, bid, tid
     • brinzolamide 1%, bid, tid

4. Non Selective Adrenergic Agonists

   • Mechanism of action
     • increase conventional trabecular and uveoscleral outflow
   • Epinephrine-related agents may initially increase aqueous production; with chronic use, they decrease it.
   • Systemic side effects include headache, increase blood pressure, tachycardia, arrhythmia, and nervousness.
   • Ocular side effects
     • Epinephrine causes adrenochrome deposits from oxidized metabolites in the conjunctiva, cornea and lacrimal system. It may stain soft contact lenses.
     • Pupillary dilation as a consequence of alpha-agonist action that stimulates norepinephrine receptors may precipitate or aggravate angle closure in susceptible individuals.
     • Allergic blepharoconjunctivitis
     • Cystoid macular edema may be precipitated or exacerbated in aphakic and pseudophakic eyes without intact posterior capsules.
     • Rebound conjunctiva hyperemia is common when they are discontinued.

   • Epinephrine(alpha and beta agonist)

   • • Epinephrine and related compounds have less hypotensive effect in eyes with dark irides.
     • The IOP-lowering effect begins at 1 hour and is maximal at 2-6 hours.
     • IOP reduction (monotherapy) by 15%-30%.
     • Tolerance, or tachyphylaxis, is common with long-term use.
     • Preparation:
       • epinephrine hydrochloride (1.0%, 2.0%, bid)
       • epinephrine borate (0.5%, 1.0%, 2.0%, bid)
       • epinephrine bitartrate (2.0%, bid)

   • Dipivefrin

   • A pro-drug that is chemically transformed into epinephrine by esterase enzymes in the cornea. Has greater corneal penetration, and its activity is relatively low.
   • Two major advantages over epinephrine salt
     • A lower topical concentration of dipivefrin has an intraocular effect similar to a higher dosage of epinephrine salt.
     • Therapeutic effectiveness in they eye can be achieved with fewer topical and systemic side effects.
     • Tolerated by some patients who are allergic to epinephrine salt.
   • Its effectiveness may be diminished if an anticholinergic agent is added because anticholinergic agent may prevent dipivefrin’s cleavage and activation bycorneal esterases.
   • Preparation: 0.1%, bid

5. Alpha-2 Adrenergic Agonists

   • Alpha1 effects include vasoconstriction, pupillary dilation, and eyelid retraction, while alpha2 effects are primarily IOP reduction and possible neuroprotection.
   • Apraclonidine and brimonidine are relatively selective alpha2 agonists that havebeen developed for glaucoma therapy. Brimonidine is much more highly selective for the alpha2 receptor than apraclonidine. Apraclonidine has a muchgreater affinity for alpha1 receptor than does brimonidine.
   • Caution is recommended when using them in patients on a MAO inhibitor ortricyclic antidepressant therapy, in patients with severe cardiovascular disease,and concomitant with beta blockers, antihypertensives, and cardiac glycosides(ophthalmic and systemic)

   • Apraclonidine Hydrochloride

   • Mechanism of action
     • Prevents release of norepinephrine at nerve terminals.
     • Decreases aqueous production and episcleral venous pressure
     • Improves trabecular outflow
   • May be effective for the short-term lowering of IOP (e.g., following argon laseriridectomy, argon laser trabeculoplasty, Nd:YAG laser capsulotomy, and cataract extraction)
   • Development of topical sensitivity and tachyphylaxis often limits long-term use. More likely to produce vasoconstriction and can prolong iris sphincter ischemia
   • Preparation: 0.5%, 1.0%. bid, tid

   • Brimonidine Tartarate

   • Encounters less tachyphylaxis in long-term use, and allergenicity such asfollicular conjunctivitis and contact blepharitis-dermatitis is also lower. Crosssensitivity to brimonidine in patient with known hypersensitivity to apraclonidine is minimal and is less likely to induce vasoconstriction.
   • Actions:
     • IOP reduction, by:
       • Decreased aqueous production
       • Increased uveoscleral outflow
     • Neuroprotection, independent of IOP reduction by:
       • Upregulation of a neurotrophin, basic fibroblast growth factor
       • Cellular regulatory genes
   • Preparation: 0.2%, bid, tid

6. Prostaglandin Analogues(PGF2α)
   • Latanoprost

   • • A pro-drug that penetrates the cornea and becomes biologically active after being hydrolyzed by corneal esterase.
     • Mechanism of action: enhancing uveoscleral outflow.
     • Can reduce IOP by 25%-35%.
     • Advantages of this agent:
       • Once-daily dosing
       • Lack of cardiopulmonary effects
       • The additivity to other antiglaucoma medications except, perhaps, higher concentration miotic agents
     • Ocular side effects:
       • Darkening of the iris and periocular skin,caused by increased numbers of melanosomes within the melanocytes. The risk of iris pigmentation correlates with baseline iris pigmentation.Blue irides may experience increased pigmentation in 10%-20% of eyes in the initial 18-24 months of therapy, whereas nearly 60% of eyes that are light brown, blue-green, or two-toned may experience increased pigmentation over the same time period.
       • Hypertrichosis of the eyelashes
       • Cystoid macular edema, uveitis, and possible herpetic keratitis.
     • Topical application is performed at night to mitigate the conjunctival injection and perhaps potentiate hypotensive effect.
     • Preparation: latanoprost 0.005%, qd

7. Medications in Combination

   • Potential benefits:
     • improved efficacy, convenience, and compliance
     • reduced cost
   • Combinations used :
     • Adrenergic agonists & parasympathomimetic agent (epinephrine & pilocarpine)
     • Adrenergic agonists & beta blockers (dipivefrin & levobunolol)
     • Beta blockers & parasympathomimetic agent (timolol & pilocarpine)
     • Beta blockers & CAIs (timolol & dorzolamide)

8. Hyperosmotic Agents

   • Common hyperosmotic agents include:
     • Oral glycerin (50% soln, 4-7oz)
     • Oral isosorbide is particularly useful oral agent for diabetic patient because it is not metabolized into sugar; 45% soln, 4-7 soln
     • Intravenous mannitol (5.25% solution, 2 g/kg body weight)
       • Used to control acute episodes of elevated IOP.
     • Mechanism of action: Increasing the blood osmolarity which creates an osmoticgradient between the blood and the vitreous humor and leads to drawing water from the vitreous cavity and hence, reduction in IOP.
     • They are rarely administered for longer than a few hours because the effects ofhyperosmotic agents are transient as a result of the rapid re-equilibration of the osmotic gradient. They become less effective over time, and rebound elevationin IOP may occur if the agent penetrates the eye and reverses the osmotic gradient.
     • The larger the dose and the more rapid the administration, the greater the reduction in IOP because of the increased gradient.

Case Studies

Case #1