Glaucoma, Suspect, Adult Clinical Presentation

Patients do not usually experience any symptoms. Intermittent headaches, haloes, and blurred vision may suggest risk for angle-closure glaucoma.

Ocular history includes the following ocular conditions that have been implicated as risk factors for developing glaucoma ^{[13, 14]} :

• Myopia: Risk factor for glaucoma; disc evaluation difficult (myopic fundus, tilted disc); visual field testing more difficult (fundus abnormalities, refraction-related inaccuracies)

• Pseudoexfoliation: Increases with advanced age

• Pigment dispersion: 25%-50% risk of developing glaucoma

• Ocular trauma

• Glaucoma in one eye: Associated with increased risk of future damage in the other eye; development of visual field defects in an average of 5 years in about 29% of untreated undamaged fellow eyes

• History of uveitis/inflammatory ocular disease

• Congenital anomalies

• Prior eye surgery

• Retinal vascular occlusion: In susceptible individuals, increased IOP associated with a risk of developing central retinal vein occlusion (CRVO)

• Current or past use of steroids: Topical steroids may elevate pressure in certain individuals; optic nerve damage may be residual from previous increased IOP associated with steroid use; the elevation of IOP is usually seen within a few weeks of starting topical steroids

Systemic history includes the following conditions that have been associated as risk factors for developing glaucoma ^{[13, 14]} :

• Low blood pressure: Also includes overmedication of systemic hypertension

• A previous episode of hypotensive shock, trauma, vascular surgery, or hemorrhage can be significant; it may indicate that optic nerve damage is not progressive but may have been a onetime insult

• History of vasospastic disorders: A higher prevalence of migraine headaches and Raynaud syndrome exists with normal-tension glaucoma

• Medications: In susceptible individuals, steroids may cause a rise in IOP; anticholinergics (antihistamine and antipsychotics) may precipitate angle-closure glaucoma

• Cardiovascular disease may be a factor in low-tension glaucoma

• Hypertension

• Diabetes mellitus: Small association; some studies have reported a higher prevalence of increased mean IOP and POAG with diabetes mellitus; diabetes is a questionable risk factor for glaucoma (association may be a result of self-selection into the health care system)

• Smoking ^[15]

• Omega-3 fatty acids have been associated with a protective effect ^[15]

Family history is a definite risk factor. Heritable susceptibility has been shown. Between 10-20% of patients with glaucoma have a positive family history. Ask about family history of glaucoma, especially in first-degree relatives. Family history of glaucoma in a sibling is the greatest risk factor, followed by glaucoma in a parent. Also, ask if glaucoma in other family members resulted in vision loss (the individual may have only had ocular hypertension). The Baltimore Eye Survey found that the relative risk of having glaucoma is increased 3.7-fold for individuals who have siblings with POAG.

Heritable susceptibility (genetics of glaucoma) has been shown for the following:

• POAG: Juvenile onset; genetic linkage mapped to band 1q23 ^[16]

• POAG: Adult onset ^{[17, 18]}

• Pigmentary glaucoma: Gene responsible for fragment dispersion syndrome mapped to band 7q35q36 ^[19]

• Pseudoexfoliation

• Aniridia

• Axenfeld-Rieger syndrome

• Primary congenital glaucoma

Review of old records: Note previous IOP, cup-to-disc ratios, ocular surgery, and past visual fields. (Caution: Poor agreement and observer variability can occur in disc examinations over time.)

Intraocular pressure

Elevated IOP is a definite and important risk factor for developing glaucomatous damage but is not sufficient for a diagnosis. ^{[20, 21, 14, 22]} The prevalence of POAG is higher with increasing IOP. One tenth of patients with ocular hypertension develop field loss within 10 years. Each year, about 1% of all individuals with increased IOP progress to glaucomatous damage. As many as 50% of patients with glaucomatous optic neuropathy or visual field changes have IOP of less than 21 mm Hg on initial evaluation. Some eyes undergo damage at IOP of less than 18 mm Hg; others tolerate IOP of more than 30 mm Hg.

A pressure of 10-21 mm Hg is considered normal; a nongaussian distribution occurs with a skew toward higher pressures.

The diurnal variation is as follows:

• 2-6 mm Hg - Normal

• Greater than 10 mm Hg - Variation suggestive of glaucoma

Peak usually occurs in the morning hours.

Goldmann-type applanation tonometry is the criterion standard for IOP measurement. In patients who are obese, handheld tonometry may be more accurate by minimizing strain to fit to the slit lamp.

Landers et al proposed an ibopamine challenge test to differentiate patients who are glaucoma suspect from those who have either stable glaucoma or progressive glaucoma. ^[23]

Common pitfalls in IOP measurement are as follows:

• Too much/too little fluorescence occurs

• Meridians are not averaged in patients with high astigmatism

• The upper lid is not held gently

• Patients should breathe normally

• Unless dangerously elevated, IOP is checked numerous times before initiating treatment to assess diurnal variation

• Abnormally thick corneas may result in artificially high IOP measurements by applanation tonometry, while abnormally thin corneas may result in artificially low IOP measurements

Corneal pachymetry

The Ocular Hypertension Treatment Study (OHTS) showed central corneal thickness as a significant predictor of the development of POAG. ^{[9, 20]}

Patients with a central corneal thickness of less than 555 µm had a 3 times greater risk of developing POAG than patients with a central corneal thickness of greater than 588 µm.

Slit-lamp examination

Look for signs of secondary causes/risk factors of glaucoma, as follows:

• Corneal endothelium: Krukenberg spindle; keratic precipitates; pigmentary changes on endothelial cells

• Anterior chamber angle depth: Identification of narrow occludable depth; avoidance of mydriatics in such eyes

• Iris: Mid iris spokelike transillumination defects (seen in pseudoexfoliation and pigment dispersion); dandrufflike material on pupillary margin and on lens capsule (pseudoexfoliation); neovascularization

Gonioscopy

Perform on all patients who are glaucoma suspect, and repeat it periodically. It is especially important in the following cases:

• The chamber shallows, and IOP rises

• Angle problems (eg, hyperopia, symptoms of subacute/acute angle-closure glaucoma, narrow angle) are evident

• The patient is diabetic

• Vein occlusion is present

• A history of ocular trauma exists

Evaluation of angle depth, signs, and risk factors for secondary glaucoma

Examine for the following:

• Narrow-angle depth

• Angle recession

• Heavy pigmentation of TM (pigment dispersion)

• Patchy pigmentation of TM (pseudoexfoliation)

• Hemorrhage

• Inflammatory changes

• Angle closure

• Peripheral anterior synechiae

• Neovascularization of the angle

Evaluation of the optic nerve head

The best examination method is a slit lamp combined with a 60-D, 78-D, or 90-D Hruby lens or a posterior pole lens through a dilated pupil, which offers the following benefits: ^{[24, 25]}

• High magnification

• Stereoscopic view

• Excellent illumination

• Special attention to contour and color

The normal vertical cup-to-disc ratio is 0.3. In a normal rim, the inferior portion is thickest, followed by the superior rim. Patients with myopia have larger eyes and larger discs and cups. Assessing optic nerve damage in small optic discs with minimal cupping may be difficult. ^[26] Large optic discs may appear pathologic when they actually show only physiologic cupping, especially in African Americans.

Signs of early glaucomatous damage can be subtle, as follows: ^[27]

• Generalized enlargement of cup

• Focal notching

• Superficial splinter hemorrhage

• Asymmetry of cupping between 2 eyes

• Nerve fiber layer dropout

• Asymmetry of neuroretinal rim

• Focal thinning of neuroretinal rim

• Acquired change in disc rim appearance

• Acquired change in retinal nerve fiber layer

• Nerve fiber layer deficit

• Thinning of inferior-temporal rim

• Progressive enlargement of cup

• Vertical elongation of cup

• Cupping to rim margin

• Exposure of lamina cribrosa

• Peripapillary atrophy

• Baring of circumlinear vessels

Search for other abnormalities that may account for the visual field defect, as follows:

• Tilted disc

• Disc drusen

• Optic pits

• Retinal disease

• Optic atrophy

Document the appearance of the optic nerve head. The preferred technique is baseline stereo disc photographs for future comparison. Detailed description and drawings should be obtained.

Automated techniques are as follows:

• Scanning lasers: Advantages include accurate, reproducible, and patient comfort (nondilated); a disadvantage is the cost (expensive)

• Weinreb et al found that baseline confocal scanning laser ophthalmoscopy Glaucoma Progression Scores, either alone or combined with baseline clinical and demographic factors, can be used to predict the development of primary open-angle glaucoma, and are as effective as stereophotographs in ocular hypertensive patients in predicting the development of primary open-angle glaucoma. ^[28]

• Polarimetry - Advantages include accurate and reproducible. A disadvantage is the cost (expensive).

Evaluation of the retinal nerve fiber layer

Look for nerve fiber layer defects/dropout.

Techniques are as follows:

• Ophthalmoscopic examination with red-free (green) filter

• Good color photography

• Red-free photography

Instruments for retinal nerve fiber layer analysis are very accurate, but they are expensive. ^[29] Sehi et al have shown that progressive atrophy of the retinal nerve fiber layer has been associated with subsequent visual field loss. ^[30] Miki et al found that faster retinal nerve fiber layer thinning corresponded to an increased risk of developing visual field defects. ^[31]

Visual field testing

Results of visual field testing should be normal.

Absence of visual field defects does not ensure absence of glaucoma.

As many as 50% of optic nerve fibers in a single optic nerve may be damaged before visual field defects are found by Goldmann perimetry.

Common pitfalls in visual field testing are as follows:

• Pupillary diameter should be maximized

• Correct refraction should be used

• Patient reliability is limited in some cases

Interpretation of visual field testing: Use comparable tests when comparing fields. For example, one cannot directly compare Swedish interactive thresholding algorithm (SITA) with Fastpac or HVF 30-2 threshold testing. If a field defect is detected, ensure that it is reproducible. The abnormal points should be contiguous, paralleling the pattern of the nerve fiber layer in an arcuate pattern respecting the horizontal midline. The greater the abnormal points and the deeper the defects, the more likely it represents a true scotoma.

The standard testing strategy used by many ophthalmologists in past evaluations has been HVF 30-2 or 24-2 traditional threshold testing with statistical analysis.

Humphrey Fastpac requires less testing time; decrease in precision of threshold algorithm estimate.

SITA reduces testing time by about 50% without sacrificing accuracy. Less interindividual variability occurs, and gray scale printouts may look lighter.

Short wavelength automated perimetry (SWAP) uses blue target on a yellow background to isolate those visual pathways that are believed to be damaged selectively in early glaucoma. Many studies suggest that it is capable of earlier detection of glaucomatous defects, which may be useful in detecting progression to glaucoma in those patients who are glaucoma suspect and at a high risk. ^{[32, 33]} It requires longer testing time with 3-minute adaptation to yellow background.

Frequency-doubling technology perimetry uses a coarse striped grating of rapidly alternating dark and light bands. It takes 4-5 minutes for each eye; screening test takes less than 1 minute. A potential role exists in diagnosing early glaucoma and in detecting moderate-to-advanced glaucoma. ^[34] Liu et al suggest that frequency-doubling technology is effective in monitoring visual field progression and that it may detect field defects earlier than standard automated perimetry. ^[35]

Risk factors that are associated with developing glaucomatous damage include the following:

• Elevated IOP

• Suspicious optic nerve head appearance

• Nerve fiber layer defects

• Increasing age

• Family history of glaucoma

• African American ethnicity

• Myopia

• Diabetes mellitus

• Pseudoexfoliation

• Pigment dispersion

• History of ocular trauma with associated angle recession

• History of uveitis

• Glaucoma in one eye

• Narrow anterior chamber angle depth

• Prior eye surgery

• Steroid use

• Migraine headache

• Cardiovascular disease

• Tight neck tie ^[36]

The greater the number and the degree of risk factors, the greater the risk of developing glaucoma over time.

Some risk factors, such as pigment dispersion, increased IOP, suspicious optic nerve head appearance, increasing age, glaucoma in one eye, pseudoexfoliation, a strong family history of glaucoma, and race (ie, African American), are more important than other factors.