Significant History

A family history of POAG and a personal history of vascular disease are considered significant risk factors by many authorities.

Ancillary Tests

• Threshold visual fields
  
• Pachymetry
  
• Optic nerve photography (stereo)
  
• Optic nerve and/or retinal nerve fiber layer imaging (HRT III, VCC GDx, OCT)
  
• Gonioscopy

The Treatment

The initial management is generally close observation. The OHTS demonstrated that patients with OHT are at risk for vision loss but that damage is generally slowly progressive and that most patients will never require treatment. It is critical to identify those patients at greatest risk (high IOP, thin CCT, large cup/disc ratio) and treat those patients. Treatment is usually topical medical therapy. Laser trabeculoplasty or surgical intervention would only be considered under extraordinary conditions without demonstrable visual field or optic nerve damage.

Initial Medical Therapy

The following medications are options for initial therapy:

• Topical prostaglandin analogs (latanoprost 0.005%, travoprost 0.004%, or bimatoprost 0.01% or 0.03%) once a day, typically at bedtime
  
• Topical β-blocker (timolol 0.25% to 0.5%, levobunolol 0.25% to 0.5%, betaxolol 0.25% or carteolol 1.0%) qam or b.i.d.
  
• Topical brimonidine 0.1% or 0.2% three times a day
  
• Topical carbonic anhydrase inhibitors (dorzolamide 2% or brinzolamide 1%) three times a day

Primary Open-Angle Glaucoma (POAG)

G. Richard Bennett and Fiaz Zaman

ICD-9: 365.11

     THE DISEASE

Pathophysiology

POAG is a progressive optic neuropathy that is associated with an elevated IOP, progressive cupping of the optic nerve, and visual field loss. IOP is thought to be elevated because of an obstruction to aqueous outflow through the trabecular meshwork.

Etiology

While the exact etiology is unclear, elevated IOP plays an important role in the development of POAG. Glaucoma probably has a polygenetic mode of inheritance.

The Patient

Clinical Symptoms

POAG is usually asymptomatic. In advanced stages, the patient may complain of decreased peripheral or central vision.

Clinical Signs

Ancillary Tests

• Threshold visual fields
  
• Pachymetry
  
• Optic nerve head photography (preferably stereo images)
  
• Optic nerve and/or retinal nerve fiber layer imaging (HRT III, GDx, OCT)
  
• Color vision testing
  
• Diurnal IOPs
  
• Gonioscopy

The Treatment

There is not a “cookbook” for the treatment of POAG. Each patient must be considered individually to determine the appropriate treatment and aggressiveness of treatment. Factors to consider include age of the patient, medical history (avoid topical β-blockers in patients with emphysema, asthma, heart block, decompensated heart failure, symptomatic bradycardia), ocular history (prostaglandin analogs may exacerbate epithelial HSV keratitis, CME), drug allergies, comfort, convenience, and compliance. Finally, each practitioner should consider the safety, cost, dosage frequency, side effects, and efficacy of all medications.

Topical medical treatment may include

1. Prostaglandin Analogs

Prostaglandin analogs have become the major first-line drug in the treatment of open-angle glaucoma because of superior efficacy, convenience, and safety.

2. Topical β-blockers

Topical β-blockers were traditionally the first line of medical therapy unless contraindicated by medical conditions.

A. Selective β-blockers

• Betaxolol (Betoptic 0.5% twice a day, Betoptic-S 0.25% twice a day)

B. Nonselective β-blockers

• Timolol maleate (Timoptic 0.25% twice a day, Timoptic 0.5% twice a day, Timoptic XE 0.25% or 0.5% qam, or Istalol 0.5% qam)
  
• Timolol hemihydrate (Betimol 0.25% or 0.5% twice a day)
  
• Levobunolol (Betagan 0.25% or 0.5% every day or twice a day)
  
• Metipranolol (Optipranolol 0.3% twice a day)—may be associated with uveitis

C. Nonselective with intrinsic sympathomimetic activity (ISA):

• Carteolol (Ocupress 1.0% twice a day)

D. Combination with dorzolamide (Cosopt twice per day = 0.5% timolol maleate + 2.0% dorzolamide)

• Combination with brimonidine (Combigan twice per day = 0.5% timolol maleate + 0.2% brimonodine)

3. Topical Carbonic Anhydrase Inhibitors (CAIs)

• Dorzolamide (Trusopt 2.0% three times a day)
  
• Brinzolamide (Azopt 1.0% three times a day)

4. Miotics

Note: Miotics are not commonly used in the United States today because of newer, more effective medications with fewer side effects.

5. Epinephrine compounds (not commonly used in the United States today)

• Dipivefrin (Propine 0.1% twice a day)
  
• Epinephrine 1% to 2% (Epifrin once or twice daily)

6. α-Agonists

• Apraclonidine (Iopidine 0.5% to 1% three times a day)—not generally used as a maintenance drug because of significant tachyphalaxis. Very useful in short-term lowering of IOP.
  
• Brimonidine 0.2% three times a day, 0.1% with Purite (Alphagan-P) preservative three times a day.

Oral Medical Treatment

Note: Oral medical treatment may be used in urgent care for very elevated IOPs but is used rarely today for chronic treatment of POAG because of significant side effects.

1. Carbonic Anhydrase Inhibitors

• Methazolamide (25- or 50-mg tablets) 25 to 100 mg orally two to three times a day
  
• Acetazolamide (250 mg tablets orally four times a day or 500-mg sustained release capsules orally twice a day)

Laser and Surgical Therapy

1. Laser Surgery

• Argon laser trabeculoplasty (ALT) is effective in reducing the IOP in approximately 70% to 80% of patients with POAG. The IOP frequently increases over time, and the success rate drops to 40% to 50% after 5 years.
  
• Selective laser trabeculoplasty (SLT) is as effective as ALT and may be repeatable after the treatment effect decreases over time.

2. Filtration Surgery

• Trabeculectomy has an 80% to 90% success rate in lowering IOP to ≤21 mm Hg in patients with POAG. Antimetabolites, such as 5-FU and Mitomycin-C, are useful in cases that are at an increased risk for failure.

3. Other Surgical Options

• Glaucoma drainage devices or tube shunt (Molteno, Baerveldt, Ahmed, etc.)
  
• Cyclodestructive procedures (cyclo- cryotherapy or laser transscleral cyclophotocoagulation, or endophotocoagulation of the ciliary processes)
  
• Nonpenetrating procedures (viscocanalostomy, canaloplasty, transciliary filtration)

Low/Normal-Tension Glaucoma (NTG)

G. Richard Bennett and Fiaz Zaman

ICD-9: 365.12

     THE DISEASE

Pathophysiology

Etiology

NTG has been shown to be a pressure-dependent disease, with IOP lowering of 30% or more often proving beneficial in slowing the rate of progression. The etiology is elusive with non-IOP–dependent risk factors such as systemic hypotension, cardiovascular disease, atrial fibrillation, migraine syndrome, vasospasm, connective tissue disorders, anemia, sleep apnea, and hypothyroidism, potentially contributing to the disease process.

The Patient

Clinical Symptoms

Like many other types of glaucoma, patients are usually asymptomatic until the optic nerve damage is severe enough to cause significant visual loss.

Clinical Signs

The diagnosis of NTG should be approached as one of exclusion. Suggested testing includes

• Automated visual fields—defects tend to be more focal, deeper and closer to fixation.
  
• Stereoscopic evaluation of the optic nerve (with a 60 or 78-D lens, fundus contact lens, or Hruby lens). Patients with NTG have a greater incidence of zone beta parapapillary atrophy (PPA) and more frequent disc hemorrhages than patients with POAG.
  
• Pachymetry is indicated as thin corneas can underestimate the true IOP.
  
• Gonioscopy excludes intermittent angle closure and other secondary causes of glaucoma.
  
• Optic nerve and/or retinal nerve fiber layer imaging (HRT III, GDx, OCT).
  
• Color vision testing.
  
• Hematologic studies including a CBC (for anemia or polycythemia), RPR, FTA-ABS (for syphilis), ANA (for connective tissue disorders), and an ESR and CRP (for temporal arteritis in the elderly) may be useful in some cases.
  
• Blood pressure and pulse should be measured and tilt testing should be considered. Some patients may benefit from ambulatory blood pressure monitoring.
  
• Diurnal IOP measurements (IOP measurements at different times of the day) should be obtained prior to initiating therapy to identify large variations in IOP.
  
• It may be appropriate to have the patient see an internist for a complete exam, emphasizing the need to investigate for cardiovascular disease and carotid occlusive disease.
  
• Neuroimaging (CT scan or MRI) should be considered in unusual or atypical cases, such as
  

  1. Patients less than 50 years of age

  
  

  2. Visual fields that are rapidly progressive, out of proportion to optic disc changes, or show defects that respect the vertical midline

  
  

  3. Central vision loss (<20/40)

  
  

  4. Asymmetry of the nerves or visual fields with symmetrical IOPs

  
  

  5. Discs that show more neuroretinal rim pallor than cupping

One should also be suspicious when finding an APD that does not correspond to the degree of asymmetry in the visual fields or the optic discs.

The Treatment

Treatment for low-tension glaucoma is similar to POAG. The IOP should be lowered by at least 30% below the level where damage has occurred, which is often best identified by diurnal measurements. While not all untreated patients with NTG show progression, a faster rate of progression has been observed in women, patients with migraine headaches, and in the presence of disc hemorrhages.

Reduction in pressure may be accomplished by medical therapy, laser trabeculoplasty, or filtration surgery. Once the target IOP has been achieved, IOP measurements should be obtained at various times of the day to exclude diurnal fluctuations.

Medical Therapy

One should consider initiating a monocular trial of the medication so that the contralateral eye can be used as a control to access efficacy and adverse effects.

Laser and Surgical Therapy

• ALT or SLT may be effective in some low-tension patients; however, the results have been inconsistent.
  
• Filtration surgery is used when progressive optic nerve cupping and visual field loss occur and there is significant danger of loss of quality of life and the IOP cannot be lowered with more conservative therapy.

Steroid-Induced Glaucoma

G. Richard Bennett and Fiaz Zaman

ICD-9: 365.03

     THE DISEASE

Pathophysiology

Steroid-induced elevations in IOP appear to be secondary to decreased facility of aqueous outflow. There are several proposed mechanisms: (a) structural changes of the trabecular meshwork, (b) mechanical obstruction of the trabecular meshwork by steroid particles, extracellular matrix, or glycosaminoglycans, (c) debris in the trabecular meshwork because of inhibition of phagocytosis by trabecular meshwork cells, or (d) steroid-induced proteins (myocilin) may initiate the response.

Etiology

Elevated IOP has been associated most commonly with the use of topical steroid eyedrops or periocular repository steroid injections. The pressure response can occur within a week or may be delayed for months or years. Systemic steroids, steroid creams used on the skin near the eye or in areas away from the eye, inhaled steroids, injected steroids, implantable steroids, and nasal corticosteroids have all been associated with an increase in IOP.

The Patient

Clinical Symptoms

The patient is usually asymptomatic unless the IOP increases enough to cause corneal edema (decreased vision, halos, photophobia) or pain. The patient may have symptoms from the ocular disorder that is being treated with steroids (photophobia from iritis).

Clinical Signs

Demographics

Steroid-induced elevations in IOP are more common in glaucoma suspects and patients with preexisting glaucoma, high myopes (>5 D), diabetics, and in those with a family history of glaucoma.

Approximately one third of the normal population will develop a moderate increase in IOP following topical ocular corticosteroid use; however, 5% to 6% will show a markedly elevated IOP response.

Significant History

Significant history includes the type of steroid and the duration of use, previous ocular disorders, a history of diabetes mellitus or myopia, or a family history of glaucoma.

Ancillary Tests

• Threshold visual fields
  
• Stereo disc photographs
  
• Gonioscopy
  
• Pachymetry is indicated as thin corneas can underestimate the true IOP.
  
• Optic nerve and/or retinal nerve fiber layer imaging (HRT III, GDx, OCT)

The Treatment

Steroid-induced IOP elevations almost always respond within days to weeks of discontinuing the steroid. It is not always possible to abruptly stop the steroid because of the underlying ocular disorder being treated. In patients with iritis, it is often difficult to determine whether the increased IOP is because of steroids or inflammation. If iritis is still present, the steroid should be continued to treat the inflammation, with the addition of medical therapy to reduce the IOP. When the inflammation has decreased, the steroid can be tapered.

Options for treatment include

Glaucoma Associated with Inflammation

G. Richard Bennett

Fiaz Zaman

ICD-9: 365.62

     THE DISEASE

Pathophysiology

Intraocular inflammation can cause an elevated IOP by several different mechanisms. Inflammation can increase resistance to aqueous outflow by causing dysfunction or swelling of trabecular sheets and endothelial cells, or by causing a breakdown in the blood–aqueous barrier, allowing inflammatory cells or fibrin to accumulate in the trabecular meshwork. Production of inflammatory prostaglandins may produce elevated IOP by causing a breakdown in the blood–aqueous barrier. If posterior synechiae, secondary to inflammation, obstructs the flow of aqueous humor from the posterior to the anterior chamber, the peripheral iris will bow forward, causing iris bombe. This bowing can cause acute or chronic angle-closure glaucoma. Peripheral anterior synechiae formation may cause chronic angle-closure glaucoma. In many instances, multiple mechanisms occur simultaneously.

Etiology

There are many etiologies of intraocular inflammation (see sections on “Uveitis”). Frequently, the cause of iridocyclitis is never determined.

One must distinguish uveitic glaucoma from angle-closure glaucoma, which may produce a mild to moderate iritis.

The Patient

Clinical Symptoms

Photophobia, red eye, pain, and decreased vision may be present.

Clinical Signs

Elevated IOP, ciliary flush, flare and cells in the anterior chamber and anterior vitreous, miosis, keratic precipitates, and engorged iris vessels may be seen. Gonioscopy is important to determine whether the angle is open or whether peripheral anterior synechiae partially or completely close the angle. Chronically elevated IOP may cause optic nerve and visual field changes.

Demographics

The demographics of the group at risk will depend on the etiology of the intraocular inflammation.

Significant History

• Previous history of intraocular inflammation
  
• Duration of current symptoms
  
• Presence of systemic diseases associated with intraocular inflammation
  
  
  
  • Sarcoidosis, tuberculosis, syphilis, etc.
    
  • Ankylosing spondylitis
    
  • Juvenile idiopathic arthritis
    
  • Behçet’s disease, ulcerative colitis, Crohn’s disease, etc.
  
  
• History of trauma

Ancillary Tests

See the section on “Uveitis” for the evaluation and suggested ancillary testing for suspected etiologies of intraocular inflammation. Secondary causes of glaucoma should specifically be excluded. Usual glaucoma testing (visual fields, gonioscopy, optic nerve photography, etc.) may be indicated in some patients.

• Topical steroids are titrated, depending on the severity of intraocular inflammation. The specific steroid used will depend on the amount of inflammation and how well the IOP can be controlled. Traumatic uveitis may not require aggressive therapy, while some inflammatory situations require frequent (every hour) instillation of steroids. Prednisolone acetate 1.0% and dexamethasone 0.1% are potent anti-inflammatory agents and are very useful in treating moderate to severe inflammatory disease. However, these agents often show a higher incidence of steroid-induced elevated IOP when compared to “soft steroids” such as fluorometholone 0.1% or 0.25%. Rimexolone 1% or loteprednol 0.5% also offer potent anti-inflammatory properties with a potentially lower incidence of IOP elevation than prednisolone acetate, prednisolone phosphate, or dexamethasone. Certain inflammatory conditions (epithelial herpes simplex keratitis, fungal infections, etc.) may preclude intervention with topical steroids.
  
• Periocular or systemic steroids are sometimes indicated for severe inflammation or inflammation that is not responsive to topical steroids.
  
• Cycloplegic eye drops, one to three times per day (scopolamine 0.25%, homatropine 5.0%, cyclopentolate 1.0%, or atropine 1.0%), are used to decrease pain from ciliary spasm and decrease the potential for posterior synechiae.
  
• Topical nonsteroidal anti-inflammatory drops (ketorolac 0.5%, diclofenac 0.1%) are sometimes helpful as an adjuvant to topical steroids. They are titrated according to the level of inflammation.
  
• IOP Management
  
  
  
  • Topical β-blockers (timolol 0.25% to 0.5% twice a day, levobunolol 0.25% to 0.5% twice a day, Timoptic XE 0.25% to 0.5% once a day, carteolol 1.0% twice a day, betaxolol 0.25% to 0.5% twice a day)
    
  • Carbonic anhydrase inhibitors (dorzolamide 2% or brinzolamide 1% drops three times a day, methazolamide 25 to 50 mg one to two tablets orally two to three times a day, acetazolamide 250 mg orally four times a day or 500-mg sustained-release capsules twice a day)
    
  • Topical apraclonidine 0.5% three times a day or brimonidine 0.1% or 0.2% three times a day
    
  • Oral or intravenous osmotic agents if the initial pressure is very high (oral isosorbide 45% 1.0 to 1.5 g/kg, oral glycerol 50% 1.0 to 1.5 g/kg or IV mannitol 20% 1 to 2 g/kg over 45 to 60 minutes)
    
  • Occasionally glaucoma filtration surgery with local antimetabolite therapy (mitomycin-C or 5 FU) is indicated if the IOP cannot be controlled medically

Note: Miotics (pilocarpine), prostaglandin analogs, and laser trabeculoplasty should be avoided while inflammation is present.

• The underlying systemic disease, if present, should be treated.

Glaucomatocyclitic Crisis (Posner-Schlossman’s Syndrome)

Nicky R. Holdeman

ICD-9: 364.22

     THE DISEASE

Pathophysiology

Glaucomatocyclitic crisis is an unusual type of acute, typically unilateral, recurrent uveitis, and secondary glaucoma.

Etiology

While the exact etiology has yet to be defined, herpes virus, cytomegalovirus (CMV), and prostaglandin E have all been implicated as possible causes. Helicobacter pylori infection has been shown to occur significantly more often in Posner-Schlossman’s syndrome (PSS) patients than in the general population.

Some research has shown that about half of all presumed cases of PSS are CMV positive, but there are no clinical features that can differentiate between CMV-positive and CMV-negative eyes.

Increased levels of prostaglandins in the anterior chamber may account for the decreased facility of outflow and breakdown of the blood–aqueous barrier.

The Patient

Clinical Symptoms

In general, symptoms are remarkably mild and few in relation to the magnitude of the IOP.

The patient may be asymptomatic, or may report slight discomfort, redness, blurred vision, and halos if the IOP is significantly elevated and corneal epithelial edema is present.

Clinical Signs

Glaucomatocyclitic crisis is generally unilateral and is associated with a significant increase in IOP (>30 mm Hg and often between 40 and 60 mm Hg). Inflammation is minimal. There are a few cells and mild flare in the anterior chamber (grades ½ to 2+). Keratic precipitates appear for a few days; are small, flat, and nonpigmented; and tend to appear in the lower third of the cornea. There may be mild corneal epithelial edema and the conjunctiva will have only minimal injection. The angle is open, and there are no anterior or posterior synechiae. Slight pupillary constriction, dilation, or slowly reactive pupil may be observed in the affected eye.

Between attacks, all tests are within normal limits, including the IOP and outflow facility. On occasion, a “sentinel” keratic precipitate is seen during the quiescent phase.

Demographics

Usually occurs in patients between the ages of 20 and 50 years and is seldom seen after the age of 60.

Significant History

The patient may report intermittent episodes of unilateral blurred vision and ocular discomfort, as recurrent attacks are common. Recurrences tend to manifest at intervals of a few months to several years.

Ancillary Tests

The implication of CMV as an etiologic agent may be important, as effective treatments for CMV infection exist and have been used for many years. Confirmation of aqueous CMV, by polymerase chain reaction (PCR), would be a prerequisite before considering systemic antiviral agents (i.e., valganciclovir, gancyclovir) in these patients.

There appears to be an association of glaucomatocyclitic crisis with primary open-angle glaucoma. Some patients can experience optic nerve cupping and visual field loss due to repeated attacks or due to underlying POAG. Consequently, patients with PSS should undergo a complete glaucoma evaluation of both eyes (e.g., gonioscopy, pachymetry, nerve fiber layer analysis, stereoscopic disc photos, and baseline visual field-testing).

It is always prudent to exclude other common etiologies of uveitis by requesting an RPR, FTA-ABS, HLA-B27, and a CXR.

Glaucomatocyclitic crisis is self-limited and will usually resolve with or without treatment. The episodes typically last from several hours to a few weeks. Between attacks, the patient is asymptomatic, the IOP is normal, and there is no intraocular inflammation.

The treatment of glaucomatocyclitic crisis is aimed at controlling the IOP, decreasing inflammation, and maintaining ocular comfort during an acute attack. Further study will be required in order to elucidate the relationship between H. pylori infection and PSS and to determine if treatment for H. pylori may improve the clinical course of the disease.

During an acute episode, treatment may include

• Topical β-blockers q.d. or b.i.d.
  
• Topical α-agonists b.i.d.–t.i.d.
  
• Topical carbonic anhydrase inhibitors or oral CAI if necessary
  
• Topical steroids—prednisolone acetate 1% q.i.d.
  
• Cycloplegic agents if needed for comfort. Cycloplegics are seldom required as there is little ciliary muscle spasm and synechiae do not form.
  
• Oral NSAIDs and topical NSAIDs may be effective in reducing inflammation and in lowering the IOP in some patients.
  
• Should a CMV infection be confirmed, valganciclovir is a potential treatment. However, valganciclovir is an expensive medication with potential for renal and bone marrow toxicity.

Note: Patients with PSS may show an elevated IOP in response to topical steroids. Prolonged treatment with corticosteroids should be avoided.

Uveitis has been considered a relative contraindication to the use of PGAs due to the risk of inflammation and CME that have been reportedly associated with this class of glaucoma medications. Recent studies suggest that these problems are not likely to occur, and that patients with uveitic glaucoma may benefit from the significant IOP lowering effects of these drugs. However, it might be prudent to avoid PGAs in favor of other medications if possible and to use them as a latter option before proceeding to more invasive interventions.

Laser trabeculoplasty (ALT/SLT) is generally not effective in controlling the elevations in IOP associated with PSS.

Neovascular Glaucoma (NVG)

G. Richard Bennett and Fiaz Zaman

ICD-9: 365.63

     THE DISEASE

Pathophysiology

Retinal hypoxia and ischemia, leading to subsequent release of angiogenic factors such as vascular endothelial growth factors (VEGFs), provides the stimulus for neovascularization of the retina, iris (NVI), and the anterior chamber angle (NVA). Neovascularization of the anterior chamber angle consists of a fibrovascular membrane that can obstruct outflow through the trabecular meshwork either by covering the anterior chamber angle or by contracting, which causes peripheral anterior synechiae formation.

Etiology

The most common causes of retinal hypoxia, resulting in NVG, are diabetic retinopathy, central retinal vein occlusion (CRVO), and ocular ischemic syndrome (carotid occlusive disease). Some of the other etiologies include branch retinal vein occlusion, central retinal artery occlusion, chronic retinal detachment, chronic uveitis, intraocular tumors, radiation therapy, and trauma.

Clinical Symptoms

Occasionally NVG is asymptomatic. More often, symptoms include red eye, pain, decreased vision, and photophobia. Nausea, vomiting, and headache may be reported if the elevation of IOP is acute and/or the IOP is very high.

Clinical Signs