Ординатура / Офтальмология / Английские материалы / Clinical Ocular Pharmacology 5th edition_Bartlett, Jaanus_2008

Box 34-3 Patterns of Visual Field Defects

Associated With Glaucoma

Nasal step

Partial arcuate

Arcuate

Paracentral

Temporal wedge (less common)

from three to one; however, the clinician must do this with the knowledge that significantly different, even normal, results may be produced with subsequent testing. Under these circumstances the clinician must decide if, taken in its totality, the evidence supporting a diagnosis of glaucoma still exists.

Visual Field Analysis in Advanced Glaucoma. When visual field loss extends into the central 10 degrees of fixation, it is recommended that some form of central visual field testing be used (e.g., 10-2 test pattern). The central test strategies use a significantly greater number of test points within the central 10 degrees. In areas where retinal sensitivity is consistently measured as 0 dB or <0 dB (the patient did not respond to the brightest stimulus available for a given instrument), a larger test target may be used (e.g., stimulus size V), but this is at the expense of sensitivity to change (much more retinal structural loss or dysfunction must occur to lower sensitivities to a larger stimulus). In addition, many of the available visual field testing strategies are based on the use of stimulus size III targets. For instance, use of stimulus size V in the 10-2 Humphrey test pattern precludes the use of the Swedish Interactive Threshold Algorithm and the progression analysis software.

Future Directions for Visual Field Analysis. Future developments in visual field analysis will likely incorporate each of the desirable elements of existing strategies. For instance, test stimuli will be introduced that produce less test–retest variability and a more rapid test time, but not at the expense of sensitivity to change. An example of this is contrast sensitivity perimetry, which uses 0.4 cycle/deg sinusoidal patches (Gabor stimuli) to measure contrast sensitivity in glaucomatous defects showing good sensitivity to defect and low test–retest variability even in regions of reduced sensitivity. In fact, reliable and repeatable measurements are obtainable even when sensitivity to standard perimetry is at 0 dB in areas corresponding to quadrants of the optic nerve head that are cupped to the rim.This ability to measure retinal sensitivity in the presence of advanced glaucoma may make this a particularly useful strategy. In addition, these stimuli, with slow temporal modulation, have a theoretical advantage over high temporal modulation stimuli (e.g., frequency doubling technology) that are more subject to the effects

of prereceptoral factors (pupil size, media opacity) and issues of adaptation. Contrast sensitivity perimetry has provided reliable measures of visual sensitivity with low variability in quadrants with dense scotomas and where clinical optic nerve assessment found little if any visible neuroretinal rim.

Clinical Pearls

•Variability should be expected, especially in areas of decreased sensitivity.

•A baseline should be established and all significant findings confirmed.

•Poor data (unreliable fields due to fixation or other patient factors) should be removed from the analysis.

• Periodically, a central visual field (e.g., 10-2, with 14 points per quadrant in the central 10 degrees) versus a peripheral field (e.g., 24-2, with 3 points per quadrant) should be used when field loss projects into the central 10 degrees.

•Do not expect visual field findings to correspond to the structural assessment of the optic nerve or retinal nerve fiber layer in early glaucoma.

TREATMENT

The goal of the management of glaucoma is to minimize, to the extent possible, the probability that a given patient, in their lifetime, will suffer a visual disability and/or diminished quality of life as a result of or due to treatment of their glaucoma. Most cases of glaucoma, given enough time, progress. As such, the focus is on managing risk as opposed to curing a disease. Unfortunately, from the onset of the condition it is not possible to predict with any meaningful degree of certainty the rate of progression or life span of an individual patient.

The Decision to Treat

The decision to treat a glaucoma patient is made after careful consideration of, among other things, the patient’s needs, medical and surgical history, age, and abilities (e.g., to self-medicate) and the practitioner’s treatment philosophy.

It might seem self-evident that if a patient has glaucoma, he or she should be treated by some means. Although all glaucoma patients should be offered therapeutic intervention, some may opt, justifiably and with concurrence of the practitioner, for careful observation. Of course, this depends, in part, on confidence that the patient will adhere to a regular follow-up schedule.An example might include a patient with a terminal medical condition and early glaucoma or a patient of very advanced age, poor medical health, and very early signs of glaucoma. In these instances, the patient should be made aware of the findings, the natural history of the type of glaucoma diagnosed, and the treatment options. Because, in general, primary open-angle glaucoma progresses slowly,

686 CHAPTER 34 The Glaucomas

observation may be the most appropriate management for some patients.

Risk Analysis

Because of the results of the OHTS and the familiarity with assessments of risk in other medical specialties (e.g., the Framingham study), renewed attention has been focused on the concept of risk analysis in glaucoma.The OHTS evaluated which risk factors were more common in patients with ocular hypertension who converted to glaucoma in the course of the study (Box 34-4). Because only a small percentage of patients with ocular hypertension did convert (~10%), the OHTS concluded that treatment of ocular hypertension should be reserved for patients at greatest risk of converting to glaucoma. As the number of risk factors increases for a given patient, so does the probability that the patient will convert from ocular hypertension to glaucoma. It is important to bear in mind that the results of the OHTS are best applied to patients with ocular hypertension (who, by definition, do not have glaucoma) versus the glaucoma population at large.The OHTS does not address the risk of progression of an established glaucoma patient. Therefore, caution should be exercised when applying the results of this or any other study to the general population of glaucoma patients. The concept of risk analysis in glaucoma will likely continue to mature with time, although it is not without its challenges. Unlike the studies of cardiovascular morbidity and mortality (e.g., the presence of a myocardial infarct or cardiovascular death), the “end point” in glaucoma studies is more challenging to define. There is far less disagreement over which patient has suffered from a heart attack and/or died as a consequence. In contrast, glaucoma is a relatively slow symptomless disease where only one risk factor can be controlled by intervention (i.e., IOP).

In the 2002 OHTS predictive study, diabetes appeared to be protective against the development of primary open-angle glaucoma. However, diabetes mellitus was entirely self-reported and not confirmed by chart review or blood tests. Thus, these data are probably incomplete and incorrect. Subsequent extensive statistical analyses in 2007 revealed that the association of diabetes with development of primary open-angle glaucoma could not be estimated reliably in the OHTS.

Box 34-4 OHTS Risk Factors

Age

IOP > 25 mm Hg

Vertical cupping of the optic nerve head

Pattern standard deviation on visual fields

Thin central corneal thickness < 555 mcm

Target Intraocular Pressure

The target IOP is the IOP range at which the practitioner judges that the risk of progression of glaucoma is unlikely to affect a given patient’s quality of life. The target pressure can be expressed as a raw number or a percentage decrease from baseline IOP. In general, target pressures are typically set lower for younger patients with more advanced disease and higher IOPs. Practitioners use many guidelines to establish a target pressure. One approach is to establish a base pressure (e.g., express the maximum IOP as a percentage, e.g., an IOP of 30 mm Hg = 30%) and, at a minimum, lower the IOP by this percentage (30 − 9 = 21).Add to the baseline percentage additional pressure lowering for disease severity (e.g., an additional 10% for each level of severity of the disease: 10% for early, 20% for moderate, and 30% for advanced) or other factors. There are many variations on this approach, and all should be viewed as estimates and a starting point for treatment.

Clinical Pearl

•Target IOPs require periodic reevaluation, depending on the impact of treatment on the quality of the patient’s life and the stability of the patient’s glaucoma and other medical conditions.

Monocular Trials

It is generally assumed that, at least in disease-free eyes, the diurnal variation in IOP is approximately symmetric in each eye of a given individual. Following a monocular trial and a treatment period long enough to achieve a steadystate effect of the medication, the difference in IOP between the two eyes should be a result of the medication trial and not the normal diurnal fluctuation (assuming no appreciable crossover effect). In essence, the untreated eye serves as a control for the treated eye.This approach is recommended in several standard glaucoma textbooks and was used in the OHTS. The validity of this approach has been a matter of some debate because these assumptions may not apply to eyes with open-angle glaucoma. Perhaps most important, it assumes that the response to treatment of one eye accurately predicts the response to treatment of the other. In some patients it does not. However, we can increase the clinical utility of monocular trials by adding additional information to our assessment of the patient.

Diurnal Variations in Glaucoma

The maintenance of IOP is a dynamic process with peaks and troughs in a 24-hour cycle. It stands to reason that this normal disease-free cycle would be interrupted by disease-induced changes in the outflow facility of the eye (e.g., in the presence of glaucoma). There is little reason to believe that the influence of this disease would affect both eyes identically. As such, variations in the IOP

cycle would not be unexpected. Although approximately two-thirds of eyes with primary open-angle glaucoma may have symmetric diurnal curves with synchronized peaks and troughs, diurnal variations can be large in glaucoma patients, ranging on average between 6 and 11 mm Hg. Variations greater than or equal to 3 mm Hg may occur in more than 63% of glaucoma patients on stable medication regimens. This variation comprises three dynamic processes occurring together—one, the normal diurnal cycle, two, the effects of the disease on this cycle, and, three, the effects of medication on the disease and the normal cycle. Clinically, this means that an IOP reading for a patient with glaucoma varies with the time of day (and, maybe more importantly, time of night, which is not addressed in clinical practice) and the degree to which aqueous dynamics are influenced by the disease and IOP lowering medications.

Predictive Value of a Monocular Trial

Like the effects of disease on IOP, the effects of medications on IOP vary as a result of several variables, including the effects of the disease on aqueous dynamics, the magnitude of the increased IOP, and the ability of the patient to properly instill the medication.The therapeutic effects of medications may not be equivalent in each eye of a patient with glaucoma. In fact, whether expressed as an absolute value (e.g., a change in IOP from 20 to 14 after treatment, or a 6-mm decrease) or as a percentage decrease from baseline (a 30% drop from baseline), there is evidence that no correlation exists between the magnitude of IOP responses of fellow eyes of patients who had a monocular trial of glaucoma medications. It is therefore possible that the monocular drug trial does not predict second-eye IOP reductions after treatment with the same medication.As a practical matter, if a monocular trial does not achieve a desired outcome, the treatment would likely be switched to another medication, independent of how the nontreated eye responds.

Managing Variability in Monocular Trials

Knowing that the IOP of a patient treated for open-angle glaucoma is a function of a therapeutic component (the effects of the medication) and a nontherapeutic component (the effects of diurnal variation, the influence of the disease on aqueous dynamics, and regression to the mean), some attempt should be made to account for as much of this variability as possible. The most logical approach would be to measure pretreatment serial IOP in an effort to establish a diurnal curve for each particular patient. This procedure provides information regarding variations during the day and between each eye and establishes a baseline to judge the effects of therapeutic interventions. Unfortunately, apart from 24-hour serial tonometry, which is not practical in a clinical setting, practitioners are overlooking pressure readings that may be substantially higher when compared with daytime (office time) measurements.

Summary

In practice, it would be prudent to explain to patients that their IOP will vary during the day and night (this sets the stage for future instructions on the proper use of aqueous suppressants during times of physiologic higher aqueous production) and ensures the patient that different readings at each visit are not uncommon.

TREATMENT MODALITIES

Once the decision has been made to proceed with treatment, the practitioner is faced with several options as the initial intervention. In broad terms surgical, laser, or medical options are available; however, medical management is the general standard of practice for the initial treatment of open-angle glaucoma.With the advent of selective laser trabeculoplasty (SLT), this procedure is being offered to some patients for initial treatment in an effort to avoid the cost, inconvenience, and adherence issues associated with topical medications. Although there may be some theoretical advantages for some patients for SLT as an initial intervention, to date, there has been no long-term, prospective, clinical trial to assess the efficacy of this approach.

Medical Management

When medical management is deemed the most appropriate treatment option for the patient, the choice of initial treatment is based, in part, on the most appropriate means of IOP reduction (e.g., aqueous suppression, outflow facilitation, or management of inflammation or some combination thereof) and the type of glaucoma. Absent any indication for intervention via aqueous suppression (e.g., glaucoma associated with hyphema; see Special Considerations in the Treatment of Glaucoma, below) or inflammation (e.g., Posner-Schlossman syndrome), the most common initial medical intervention is the use of prostaglandins (Table 34-3). These medications work by increasing uveoscleral outflow and are often chosen as initial treatment due to their efficacy (IOP is lowered, on average, ~ 30% from baseline), their relatively good patient tolerability, low incidence of significant side effects, few contraindications, one drop a day regimen, and coverage during the nighttime hours where IOP may be the highest during the circadian cycle.

Table 34-3

Prostaglandins Used in Clinical Practice

688 CHAPTER 34 The Glaucomas

Prostaglandins

Contraindications of Prostaglandins. The use of this class of medications should be deferred in the presence of an active uveitis and should be used with caution in patients with a known history of herpes simplex keratitis or cystoid macular edema.

Side Effects. The most common side effect of prostaglandins is conjunctival hyperemia. In general, this is most common and most apparent with the use of bimatoprost. Fortunately, this side effect often diminishes over the course of months. Another well-known side effect is eyelash growth and increased pigmentation of the iris and periorbital tissue.This pigmentary change of the iris is particularly noticeable in hazel-colored irides and occurs over the course of months of treatment. The change in periorbital tissue pigmentation is generally difficult to discern if it occurs bilaterally but can become quite noticeable when patients are treated monocularly. Patients should therefore be informed of this possibility.

Because the concentration of the topical prostaglandins in the systemic circulation is lower than endogenous prostaglandins, it is not surprising that there have been few reports of significant systemic adverse events.

Use in Clinical Practice. The introduction of this class of medication significantly changed the way in which glaucoma was managed. It was not uncommon among established patients to convert from being managed on two or more medications (including oral acetazolamide) with multiple daily doses (e.g., pilocarpine four times a day) to meeting target pressures on a prostaglandin drop taken once a day.The most common complaint during the introduction of this medication class was the size, shape, transparency, and pliability of the bottle. As patients were introduced to these medications sooner in their management and as it became less common to prescribe larger volume bottles (such as pilocarpine), these initial issues became less significant.

If target pressure is not met with an initial prostaglandin, it may be useful to switch to an alternative topical prostaglandin. However, there is little scientific evidence to support this approach. In fact, in a controlled environment there is little difference in efficiency among the various prostaglandin formulations. Although there are anecdotal reports of significantly different responses to treatment within individual patients, these results are clouded by issues of compliance with the initial treatment.

Switching within this classification is useful because it keeps the patient’s regimen simple (once a day dosing) with few side effects, and with the idea that additional medications may be required if this strategy fails, the patient may be more inclined to be compliant. Because bimatoprost typically causes the greatest hyperemia and

is often least tolerated, it is advisable to start a patient on either of the other two choices and switch to bimatoprost if the alternatives have been exhausted.This has the added advantage of exposing the patient to this group of medications for a period of time, which tends to reduce the hyperemic effects of bimatoprost when compared with the effect if bimatoprost had been used initially. Care should be taken when treating a patient monocularly because the increased pigmentation can become cosmetically unacceptable.

Cholinergic Agonists

The cholinergic agonists (Table 34-4) represent another classification of glaucoma medication that functions primarily by its influence on aqueous outflow.

Indications. This classification of drugs is often useful in the management of acute ACG (once the pressure is reduced to ~30 mm Hg).The pupillary miosis and mechanical deformation of the scleral spur move synechia or appositional iris tissue from the angle and prepare the iris for laser peripheral iridotomy. In high concentrations, however, these drugs are capable of displacing the lens–iris diaphragm, which can exacerbate the closure.

Contraindications. The use of cholinergic agonists is contraindicated in the presence of acute uveitis or any condition where miosis is undesirable.

Cholinergic Agonists in Clinical Practice. This class of medications is not used as frequently as in the past. Pilocarpine is, however, an important medication to have available in the office in the presence of an acute ACG and is used to prepare the iris for laser peripheral iridotomy. There are instances where the use of miotics has theoretical advantages over other classifications of medications, such as the treatment of pigmentary glaucoma, where moving the iris away from the lens zonules might be desirable. However, there are also distinct disadvantages to these medications. The dosing, with the exception of pilocarpine ointment, is often three or four times a day.The resultant miosis, although appreciated by some patients as increased depth of focus and sharper visual acuity as a result of the pinhole effect, can reduce retinal illuminance to the point that it influences a

Table 34-4

Cholinergic Agonists Used in Clinical Practice

patient’s functional ability.This effect also had a dramatic impact on visual field testing and dilated fundus examinations.The longer the duration of treatment and the higher the concentration, the more difficult it is to obtain a satisfactory pupillary dilation. This and the loss of the suppleness of the conjunctiva with chronic use also make ophthalmic surgery (e.g., cataract, trabeculectomy) more challenging. There is some evidence that chronic miosis also may place patients at greater risk for retinal detachment. These potential complications make the use of miotics even less appealing, and with the introduction of newer classifications of medications, the use of miotics has waned.

Aqueous Suppressants

The aqueous suppressants include the β-adrenergic antagonists, α-agonists, carbonic anhydrase inhibitors (CAIs; topical and oral), and hyperosmotics (intravenous).The topical forms of this classification are used routinely in clinical practice. The oral and intravenous formulations are generally reserved for use under special circumstances.

b-Adrenergic Antagonists. The β-adrenergic antagonists (Table 34-5) were considered the first-line medication for glaucoma for many years. Before the introduction of this class of medications, the most commonly used medications were pilocarpine, epinephrine, and oral acetazolamide (Diamox). The arrival of this class offered a twice-daily topical dosing regimen with generally comparable or better IOP lowering when compared with the other topical agents. There were fewer side effects, and over time clinicians became increasingly comfortable with their use.

Side Effects and Clinical Problems Associated with Topical b-Adrenergic Antagonists

Ocular. Eye irritation,burning,tearing,and foreign body sensation can occur with the use of topical β-adrenergic antagonists; however, these effects are usually short term. Notable long-term manifestations include dry eye and

Table 34-5

β-Adrenergic Antagonists Used in Clinical Practice

tachyphylaxis; after years of use the IOP lowering effects of β-adrenergic antagonists diminish in some patients. Switching from one brand or formulation to another does not appreciably change this effect. If target pressure is not being met as a result of this loss of IOP control, it is advisable to replace the drug with an alternative class of medication.

Systemic. The systemic side effects of topical β-adrenergic antagonists are summarized in Box 34-5.These drugs are known to cause cardiovascular, respiratory, and nervous system side effects—and even death. Even with cardioselective options, this group should be used with caution in patients with known respiratory or pulmonary dysfunction.Although the safety of this class of medications periodically comes under scrutiny, the track record of these medications is now almost three decades in duration, and they continue to play an integral part in the management of glaucoma.

Contraindications and Drug–Drug Interactions of b-Adrenergic Antagonists. Contraindications to topical β-adrenergic antagonists include sinus bradycardia, secondor third-degree heart block, cardiogenic shock, uncompensated overt cardiac failure, severe bronchial asthma, or severe chronic obstructive pulmonary disease. Caution should be exercised when topical β-adrenergic antagonists are prescribed in tandem with adrenergic psychotropic, catecholamine-depleting, calcium antagonist drugs, or digitalis.

b-Adrenergic Antagonist Use in Clinical Practice.

Topical β-adrenergic antagonists remain an integral part of glaucoma management, although they are more commonly used as a second-line medication. They may work well when added to a regimen of once-at-bedtime prostaglandins because this class of medication uses a different mechanism to reduce IOP. Although the combination of these two classes (prostaglandins and betaantagonist) is available in other parts of the world, they have not received FDA approval in the United States.

Box 34-5 Systemic Side Effects of β-Adrenergic

Antagonists

690 CHAPTER 34 The Glaucomas

Topical β-adrenergic antagonists may be prescribed in once-daily dosing with adequate therapeutic effect for some patients.This effectively halves the concentration of medication that the patient receives. If twice-daily dosing is indicated, it is advisable to have the patient use the medications in the early morning and then approximately 12 hours later, which, for many patients, occurs around supper-time. Nighttime administration is not ideal because, as an aqueous suppressant, the drug is not being used to its maximum potential due to the normal physiologic circadian trough in IOP, which begins in many patients in the evening. In the setting of normal tension glaucoma, nighttime administration of topical beta-blockers should be used with caution because this class of medication may negatively influence the profusion pressure to the optic nerve head (e.g., by its influence on the heart and possibly the vessels of the optic nerve head). A prostaglandin at bedtime is a more appropriate choice to compensate for the gradual increase in IOP that occurs during the sleep cycle.

Before use of topical β-adrenergic antagonists and following a careful history to assess the potential risk to the patient, it is advisable to evaluate the patient’s blood pressure and pulse. Patients with concurrent use of oral β-adrenergic antagonists should typically avoid topical agents in the same class. Patients should be informed of the potential side effects of these medications and should discontinue their use if warranted.

a-Adrenergic Agonist Use in Clinical Practice. The α agonists (Table 34-6) represent a class of glaucoma medications that function, primarily, as aqueous suppressants, although they may also facilitate outflow.

Two α-adrenergic agonists are available on the market. Apraclonidine 0.5% is indicated when a patient on maximum tolerated medical therapy requires short-term additional IOP lowering. Before the introduction of brimonidine, apraclonidine was the only available α-adrenergic agonist and was FDA approved for short-term use. Approximately one-third of patients using apraclonidine showed little or no treatment effect. For another third the treatment effect (3 to 5 mm Hg) was short in duration (3 to 6 months); for the remainder the effect was more lasting. Consequently, this medication

Table 34-6

α Agonists Used in Clinical Practice

was used as an adjunctive treatment for some patients. Today, apraclonidine is most commonly used as a pretreatment medication to prevent spikes in IOP after glaucoma laser procedures (although brimonidine is a reasonable alternative).

Brimonidine can be used either in the short term (e.g., to prevent IOP spikes after glaucoma laser procedures) or in the long term, as an adjunctive therapy or as a first-line treatment. Although it is FDA approved for three times a day dosing, it is commonly prescribed as twice daily. Introduced as a 0.2% solution, a significant percentage of patients developed a delayed hypersensitivity reaction to this preparation. Consequently, the concentration was reduced, first to 0.15% and then 0.1%, and a new preservative was used. These changes significantly reduced the incidence of adverse reactions. IOP reductions are typically 20% to 30% (approximately equivalent to timolol maleate) in all concentrations.

Contraindications and Drug Interactions.

Apraclonidine and brimonidine are both contraindicated with concurrent use of monoamine oxidase inhibitors (Table 34-7). Patients with hypersensitivity to clonidine should not be prescribed apraclonidine. These two compounds (apraclonidine more so than brimonidine) also have the potential to interact synergistically with central nervous system depressants and β-adrenergic antagonists. With brimonidine, caution should be exercised in patients susceptible to side effects of fatigue, drowsiness, somnolence, and dry mouth and should not be used in infants and young children due to increased risks of lethargy and somnolence. Long-term use of brimonidine may produce varying degrees of systemic hypotension.

Table 34-7

Monoamine Oxidase Inhibitors and Indications

Table 34-8

Carbonic Anhydrase Inhibitors Used in Clinical Practice

Carbonic Anhydrase Inhibitors. The CAIs (Table 34-8) are aqueous suppressants not typically used as first-line medications in the treatment of glaucoma.

Use of Topical CAIs in Clinical Practice. Although, as monotherapy, this class of medication can lower IOP by ~20%, topical CAIs are generally used as adjunctive therapy either as an additional separate administration or, more commonly, in a fixed combination with timolol maleate (Cosopt). It is important to explain to patients that this medication can be uncomfortable on the eye and that they may experience a bitter metallic taste associated with its use. This side effect is far more common with dorzolamide than brinzolamide.

Serious Side Effects. Corneal decompensation in patients with preexisting endothelial compromise (e.g., Fuchs’ endothelial dystrophy) and hypotony have been reported with topical CAIs. Common adverse reactions to oral CAIs are summarized in Box 34-6.

Use of Oral CAIs in Clinical Practice. Use of oral CAIs is generally limited to the management of acute primary ACG or in cases where other efforts have been proven to be inadequate or contraindicated. In chronic use, methazolamide 25 or 50 mg three times a day generally carries a more favorable side effect profile than acetazolamide in any form. If acetazolamide must be used chronically, then 500 mg (at bedtime or twice daily) in a sustained-release form is preferred. This formulation may

Box 34-6 Common Side Effects of Oral CAIs

dampen the side effects. It is noteworthy that approximately half of all patients offered oral CAIs for chronic management of glaucoma cannot tolerate these medications long term. In addition, topical and oral CAIs do not act synergistically, and therefore there is no advantage to using both formulations together.

Both acetazolamide and methazolamide are contraindicated in

•The presence of depressed sodium and/or potassium blood serum levels

•Severe kidney and/or liver disease or dysfunction

•Suprarenal gland failure

•Hyperchloremic acidosis

•Chronic congestive ACG (long-term use)

Because CAIs are sulfonamides, care should be taken to

exclude a known sulfonamide allergy. Severe reactions to sulfonamides such as aplastic anemia, Stevens-Johnson syndrome, and fulminant hepatic necrosis are uncommon but have been known to occur. CAIs should be discontinued if any signs or symptoms of these conditions occur.

Topical CAIs are a considerably safer alternative. However, in theory, they carry the same potential risks due to systemic absorption.

TREATMENT STRATEGIES

There is no “cookbook” approach to the management of glaucoma. Each case must be tailored to suit the needs of the individual patient. In all instances proper drop instillation is very important. Patients should be reminded to occlude their puncta with each drop and wait several minutes between drops in an effort to maximize the amount of medication reaching target receptors in the eye and to minimize systemic absorption.

As a general guideline, the greater the number of times a patient must take medications during the day, the greater the likelihood of nonadherence to treatment and the greater the risk of a negative impact on the quality of an individual’s life.The following strategy is one of many possibilities that keeps this simplicity in mind and assumes no contraindications to any class of medications.

1.Start with a once-daily medication, for example,

a.Travoprost

b.Latanoprost

c.Expect ~30% reduction in IOP

2.If target pressure is not met

a.Reeducate the patient

b.Have the patient demonstrate proper drop instillation, including punctal occlusion

c.Reschedule for subsequent IOP check

3.If target pressure still not met

a.Switch within this category of medication, for example,

i.Latanoprost

ii.Travoprost, or

b.Switch to bimatoprost

692 CHAPTER 34 The Glaucomas

c.Instill a drop in the patient’s eye in office and have them return later in the day for an IOP check

d.At this point, the patient has been instilling one drop using one bottle, once a day. Further IOP reduction requires either another medication or laser trabeculoplasty (argon laser trabeculoplasty/selective laser trabeculoplasty). Alternatively, discontinuing the

prostaglandin and continuing treatment with aqueous suppressants alone (e.g., β-adrenergic antagonist, α-adrenergic agonist) is a reasonable alternative,

although, on average, less IOP reduction is expected from aqueous suppressants as monotherapy.

e.Administering the drop in the office assists in ruling out poor adherence as a variable.

4.If target pressure still not met

a.Add morning β-adrenergic antagonist

b.Increase to every 12 hours as needed (care should be taken in the patient with normal tension glaucoma)

c.Expect additional ~15 % reduction of IOP

d.At this point the patient is taking two medications, from two bottles, two to three times per day.

5.If some treatment effect but target pressure still not met

a.Discontinue β-adrenergic antagonist and replace with β-adrenergic antagonist–CAI combination

every 12 hours

b.Expect additional ~10% reduction of IOP

c.Three medications, two bottles, three times per day

6.If some treatment effect from addition of topical β-adrenergic antagonist–CAI combination, but target

pressure not met.

a.Add brimonidine twice daily

7.If target pressure still not met

a.Consider argon or selective laser trabeculoplasty

b.Consider surgical intervention (e.g., trabeculectomy)

Drug Holidays

There are times, especially when a new patient uses several glaucoma medications, that selectively discontinuing medications is indicated to help reestablish the least amount of prescribing to achieve a target pressure. It may also help the patient reestablish good medication-taking habits. As a general rule, if the patient is on two or more medications with a similar mechanism of action (e.g., aqueous suppression), then discontinuing one medication at a time from this group is the preferred approach. This is followed by an appropriate washout period and clinical follow-up. It is not uncommon to have patients discontinue medications (under clinical guidance) and find that fewer prescriptions are possible to maintain adequate control.

Special Considerations in the

Treatment of Glaucoma

Increased IOP in the Presence of Hyphema

Traumatic hyphema may lead to an increase in IOP. IOP reduction should be accomplished by aqueous suppressants.

The use of miotics is typically avoided in the management of this condition because their use may exacerbate ciliary spasm and inflammation and may increase the likelihood of peripheral anterior synechia. Prostaglandins are also avoided because this group of medications may exacerbate the inflammatory component. Increased IOP associated with hyphema is often of relatively short duration (2 to 3 days), and in the presence of a healthy optic nerve and moderately elevated IOPs (30 mm Hg), observation and daily follow-up may be all that is required to manage the IOP component. Surgical intervention (paracentesis and anterior chamber washout) should be considered in instances where IOP remains above 50 mm Hg for more than 24 hours or more than 35 mm Hg for more than a week. Surgical intervention may also be considered depending on the size and duration of the hyphema, presence of a second hyphema (rebleed), or the presence of corneal blood staining (erythrocyte products and hemosiderin deposition in the corneal endothelial keratocytes).

Increased IOP in the Hyphema Patient With Sickle Cell Disease or Trait

Sustained elevated IOPs require treatment, as does any elevated IOP associated with hyphema in a patient with sickle cell disease or trait. These patients have a higher incidence of increased IOP (sickled cells do not pass through trabecular meshwork as freely as normal red blood cells), optic atrophy, and secondary hemorrhage in the setting of traumatic hyphema compared with non–sickle cell patients.

Patients with sickle cell disease are far more sensitive to increases in IOP, even of short duration (2 to 4 days) and IOPs as low as 30–35 mm Hg. These conditions are capable of occluding the central retinal artery (due, in part, from stagnation of blood in small vessels, excessive deoxygenation of erythrocytes, erythrostasis, sickling, and increased blood viscosity). It is therefore prudent to order a sickle prep (Sickledex) or hemoglobin electrophoresis on all patients suspected of having sickle cell disease or trait (more common among African-Americans and people of Mediterranean descent) in the presence of increased IOP associated with hyphema.

Medical Management of Increased IOP in the Hyphema Patient With Sickle Cell Disease or Trait

Treatment of IOP should concentrate on aqueous suppression, and timolol and brimonidine (or apraclonidine) should be the mainstays of IOP management. CAIs (especially oral acetazolamide and methazolamide) are capable of promoting hemoconcentration and can induce systemic acidosis, which is known to exacerbate erythrocyte sickling.

The use of dorzolamide or brinzolamide (topical CAIs) has an advantage because of their suppression of aqueous production and lack of systemic acidosis. However, there is a theoretical risk of anterior chamber acidosis, and with

no study proving safety of topical dorzolamide in sickle cell disease patients with hyphema, its use should be curtailed.

Surgical Management of Hyphema Patient With Sickle Cell Disease or Trait

Surgical intervention (evacuation of the hyphema) should be considered if the IOP averages more than 24 mm Hg over any consecutive 24-hour period despite maximum tolerated medical therapy or if the IOP increases transiently and repeatedly above 30 mm Hg.

NEOVASCULAR GLAUCOMA

Neovascular glaucoma is a condition marked by new blood vessel proliferation on the iris and in the anterior chamber angle usually as a result of retinal or anterior segment ischemia/hypoxia. Neovascularization of the iris usually appears first on the surface of the iris adjacent to the pupillary border.These vessels are fine in caliber and may have aneurysm-like outpouchings. Gonioscopic evaluation may reveal vessels in the anterior chamber angle even in the absence of iris vessels.

Treatment

Prompt treatment of the underlying ischemia (e.g., panretinal photocoagulation) can prevent anterior chamber neovascularization. In the presence of neovascularization, it can often prevent neovascular glaucoma. Prompt (within 1 to 2 days) treatment of neovascularization of the iris is essential especially if accompanied by high IOP. Angle closure can occur within days to weeks. Left untreated, neovascular glaucoma can lead to no light perception, pain, and potential loss of the globe.

Medical Management

The goal of medical management is to reduce inflammation and pain. The mainstay of medical management is topical atropine 1% (three times a day) to decrease ocular congestion and prednisolone acetate 1% (every 1 to 6 hours, depending on severity) to decrease inflammation. Concurrent use of traditional aqueous suppressant antiglaucoma medications should also be used as indicated. Miotics and prostaglandins are not recommended due to the risk of increasing inflammation, and prostaglandins may exacerbate the inflammatory component.

Surgical Management

Surgical procedures are often aimed at pain management and include cyclocryotherapy, trabeculectomy, and tube implant. In general, outcomes are less successful compared with primary open-angle glaucoma.

no usable visual acuity, the focus of treatment may shift to strictly pain management with steroids and cycloplegics.

ANGLE-CLOSURE GLAUCOMA

Clinical Presentation of Acute

Primary ACG

The classic presentation of a patient with acute ACG includes complaints of eye pain, headache, blurred vision, photophobia, the perception of halos around lights, nausea, and vomiting. Clinical signs include an edematous cornea, a fixed mid-dilated pupil, ciliary injection, high IOP, convex iris (iris bombé), and cells and flare in the anterior chamber. There may also be evidence of previous episodes such as peripheral anterior synechiae, anterior subcapsular lens opacities (glaukomflecken), sector iris atrophy, an irregular pupil, and a narrow angle in the contralateral eye.

Medical Management of ACG

Acute ACG should be considered a true ocular urgency. Treatment should therefore be promptly initiated even if the patient is ultimately referred for further care. In general, medical management is aimed at reducing IOP to levels and reopening the angle to allow for subsequent treatment with laser (e.g., laser peripheral iridotomy, laser iridoplasty).

There is no universally accepted standard for the medical management of ACG. Treatment should be tailored to fit the needs of each patient, accounting for contraindications (e.g., use of β-adrenergic antagonists in the presence of asthma) and the nature of the presenting condition. The following are general guidelines for the management of acute primary ACG:

•Acetazolamide (Diamox 250 mg, 2 tablets by mouth in one dose, or 250 to 500 mg intravenously)

•Topical β-adrenergic antagonist (e.g., timolol maleate 0.5%), 1 drop

•Topical α-adrenergic agonist every 15 minutes (e.g., apraclonidine 0.5%), 1 drop

• Topical steroid (prednisolone acetate 1%) every 15 minutes three times, then every 1 hour

If the eye is phakic and the angle closure is a result of pupillary block:

•Pilocarpine 1% to 2% every 15 minutes two times and pilocarpine 0.5% 1 drop to the contralateral eye

If the eye is aphakic or pseudophakic:

• Mydriatic and cycloplegic (e.g., cyclopentolate 2%, phenylephrine 2.5% every 15 minutes four times)

•Recheck visual acuities and IOP in 1 hour. If no improvement, repeat all topicals (with the possible exception of pilocarpine as this agent may shallow anterior

USE OF HYPEROSMOTICS

Use of hyperosmotics in the United States is limited to intravenous preparations. Hyperosmotics cause increased blood serum osmolarity, which pulls water from tissues into the bloodstream. By increasing the osmotic gradient between plasma and the eye, vitreal dehydration occurs, which results in reduced ocular volume and correspon-

8 hours). Hyperosmotics are indicated when there is a need for rapid temporary reduction in high IOP.

Mannitol

Mannitol is an intravenous hyperosmotic (1.5 to 2 g/kg intravenous as 20% solution [7.5 to 10 mL/kg] or as 15% solution [10 to 13 mL/kg]) over a period as short as 30 minutes. Cardiovascular status must be carefully evaluated before rapid administration of mannitol because a sudden increase in extracellular fluid may lead to fulminating congestive heart failure.

Urea

Urea is also an intravenous preparation (1 to 1.5 g/kg; 0.45 to 0.68 g/lb [30% solution] by slow infusion; not to exceed 4 ml/min or 120 g/d). It has a lower molecular weight than mannitol and less of a diuretic effect. Urea is contraindicated in the presence of an intracranial hemorrhage. Urea may increase risk of venous thrombosis and hemoglobinuria in patients who are hypothermic.

Contraindications to Hyperosmotics

The following are contraindications for the use of hyperosmotics:

•Documented hypersensitivity

•Frank or impending acute pulmonary edema

•Anuria

•Severe dehydration

•Severe cardiac decompensation

•Active intracranial bleeding (especially mannitol, urea) Precautions should be taken in the following instances:

•Severe dehydration

•Confused mental states

•Congestive heart disease

•Other cardiac, renal, or hepatic disease

•Hypothermia (urea may increase risk of venous thrombosis and hemoglobinuria)

•Lithium levels decrease (mannitol and urea)

If IOP still does not decrease, consider laser peripheral

iridotomy if the cornea is clear enough to accomplish

GLAUCOMA ASSOCIATED WITH INFLAMMATION

Scleritis, uveitis (e.g., Posner-Schlossman syndrome), keratitis, trabeculitis (e.g., herpetic), and/or episcleritis may be associated with an increase in IOP substantial enough to cause glaucomatous optic atrophy. If the patient is a “steroid responder,” the use of corticosteroids for the treatment of these conditions may also be responsible for increased IOP.

In most cases of glaucoma associated with inflammation, the anterior chamber angle is open, and the increase in IOP results from direct involvement of the trabecular meshwork as a consequence of local inflammation (e.g., secondary trabeculitis) or preexisting outflow anomalies exacerbated by perilimbal inflammation elevating episcleral venous pressure. Less commonly, local inflammation causes an increase in IOP as result of a secondary angle closure (Box 34-7).

In most cases the treatment of these conditions involves both anti-inflammatory (typically topical corticosteroids) and antiglaucoma (typically aqueous suppressants) medications. Cycloplegics are used to prevent or manage posterior synechia, secondary neovascular glaucoma, and choroidal effusion. Miotics are typically avoided in the management of these conditions because their use

Box 34-7 Pathophysiology of Increased IOP in the Presence of Inflammation

Angle open

Local inflammation of the trabecular meshwork Response to corticosteroid treatment Inflammatory debris impeding aqueous outflow

Secondary closed angle

Peripheral anterior synechia resulting from inflammation and adherence of the iris to the trabecular meshwork

Posterior synechia, with pupillary block resulting from inflammation and adhesion of the iris to the lens or vitreous

Forward rotation of the ciliary body resulting from edema of the ciliary body and/or choroidal effusion, causing a forward displacement of the lens–iris diaphragm

Angle neovascularization as a result of chronic anterior chamber inflammation or retinal hypoxia

Treatment Corticosteroids Aqueous suppressants Cycloplegics