Normal VEP waveform in a glaucoma suspect

ICD-10 Diagnosis Codes:

Open-angle glaucoma with borderline 
findings, low risk, right eye
H40.012–Open-angle glaucoma with borderline findings, low risk, left eye
H40.013–Open-angle glaucoma with borderline findings, low risk, bilateral
H40.021–Open-angle glaucoma with borderline findings, high risk, right eye
H40.022–Open-Angle Glaucoma with borderline findings, high risk, left eye
H40.023–Open-Angle Glaucoma with borderline findings, high risk, bilateral


Open-Angle Glaucoma Suspect, low risk




A glaucoma suspect is a person with clinical findings and/or a combination of risk factors that indicate an increased likelihood of developing glaucoma.

Glaucoma is an optic neuropathy showing distinctive changes in optic nerve morphology without associated pallor. The term “glaucoma” refers to a  group of chronic, progressive optic neuropathies that have in common characteristic morphologic changes at the optic nerve and retinal nerve fiber layer.

The glaucomas are associated with the following clinical features:

  • Aqueous outflow restrictions
  • Unphysiologic intraocular pressure
  • Abnormal ocular perfusion
  • Abnormal rate of apoptosis
  • Progressive retinal ganglion cell loss
  • Characteristic changes in optic nerve anatomy


Glaucoma is a diagnosis of exclusion.  According to the 2015 ICD-10 diagnosis codes, persons are considered open-angle glaucoma suspects based on the number of risk factors they possess.  Low-risk is one or two risk factors.  High-risk is three or more risk factors.  Commonly considered risk factors include:

  • Positive family history for glaucoma
  • Black or Hispanic race
  • Elevated intraocular pressure
  • Abnormal optic disc appearance (esp. vertical C/D changes)
  • Thin central corneal thickness below 500 microns combined with elevated intraocular pressures

Additional risk factors not included in the ICD-10 listing include the following:

  • Low blood pressure
  • Sleeping / breathing disorders
  • Diabetes
  • Angle abnormalities / outflow restrictions
  • Prior trauma to globe

For patients diagnosed as glaucoma suspects, there remains some controversy on whether unphysiologic intraocular pressure is the dominant factor involved in developing glaucomatous optic atrophy or if there is a secondary component such as compromised blood flow to the optic nerve head.

Normal Optic Nerve and Optic Cup

  • The border between the optic cup and the optic disc is based on contour, not color
  • The normal optic disc has a shape that is oriented vertically
  • The normal optic cup is horizontally oval – about 8% longer in the horizontal diameter than the vertical diameter
  • Normal optic cups are symmetrical and have equal shape between the eyes
  • Asymmetry of shape not attributable to differences in refractive error or congenital anomalies is suspicious for glaucoma
  • Vertically elongated optic cups in round nerve heads is suspicious for glaucoma
Normal Neuroretinal Rim Tissue

  • Most important component of the diagnostic evaluation
  • Healthy rim tissue is even in color and maintains a relatively flat plane
  • The shape of the neuroretinal rim follows the ISNT rule:
    • the rim tissue is broadest inferiorly
    • followed by the superior region
    • followed by the nasal region
    • followed by the temporal region, where it is narrowest
  • Changes in the appearance of the neuroretinal rim most closely correlate with visual field changes
  • Glaucoma has a predilection for localized inferior and superior neuroretinal rim loss
DG36512Pic17 Changes in Coloration of the Optic Nerve

  • Mild glaucomatous atrophy
  • Pallor of the tissue is indicative of ischemia
  • Generalized pallor of neuroretinal rim is more diagnostic of optic atrophy but localized pallor is more diagnostic of glaucoma
  • Temporal neuroretinal rim pallor in combination with increased cupping is highly suspicious for glaucoma
DG36512Pic16 Changes in Coloration of the Optic Nerve

  • Advanced glaucomatous atrophy
  • Diffuse enlargement of the optic cup
  • Wipe out of all or a portion of the neuroretinal rim
  • Nasalization of the vascular tree
  • The overall disc pallor seen in advanced glaucoma is due to a more excavated cup rather than pallor of the neuroretinal rim
Changes in the Position of the Optic Cup

  • Mild glaucomatous atrophy
  • The normal optic cup is centered in the optic nerve head
  • Temporal decentration of the optic cup in the left eye
  • Temporal or inferior decentration of the optic cup is highly suspicious for glaucoma
DG36512Pic28 Changes in the Margins of the Optic Cup

  • Mild glaucomatous atrophy
  • The margin of the optic cup is typically smooth and slightly rounded
  • Very sharp or heavily sloped cup margins are suspicious for glaucoma
  • Sloping or contour of the cup margin indicates a loss of glial support tissue
DG36512Pic23 Changes in Optic Cup Depth

  • Mild glaucomatous atrophy
  • Normal eyes can have deep cupping simply due to the unique differences in individual anatomy
  • Depth of the cup is usually significant only as it relates to the width of the cup
  • Glial erosion may occur to the point that the lamina cribrosa becomes visible
  • Deepening of the cup generally occurs slowly over time
  • Deep cups that are also wide are more suspicious for glaucoma
  • It is normal for larger optic discs to have larger optic cups
  • Larger cups are normally deeper cups
Changes in Optic Cup Size

  • Mild glaucomatous atrophy
  • The size of the optic cup is what is commonly referred to as “cupping”
  • Optic cup size is represented by a fraction with the numerator indicating the size of the cup in relation to the size of the optic disc
  • Estimation of this relationship is made in both the horizontal and vertical orientations
  • Cup-to-disc ratios vary among individuals and in the normal population
  • Cup-to-disc ratio = .40/.60
Changes in Optic Cup Size

  • Moderate glaucomatous atrophy
  • Focal enlargement of the optic cup is a positive indicator for glaucoma
  • Focal enlargement is thought to be due to localized ischemia
  • Loss of tissue appears as a wedge-like bite taken out out the cup margin called a “notch”
  • Notches in the cup margin create wedge-like defects in the visual field with the apex pointing towards the blind spot
  • Inferior focal optic disc notch creates a wedge-shaped defect in the retinal nerve fiber layer
DG36512Pic15 Vessel Changes at the Optic Nerve

  • Moderate glaucomatous atrophy
  • Splinter-like optic disc hemorrhages can occur at the nerve margin
  • Collateral vessels at or near the optic nerve are also considered suspect for glaucoma – especially when seen in conjunction with other suspicious nerve head changes
  • Disc hemorrhages are detected in less than 8% of patients with glaucoma
  • Cilioretinal arteries and nasalization of vessels in an otherwise normal appearing optic cup are not indicative of glaucoma
DG36512Pic33 Loss of Retinal Ganglion Cells

  • Moderate glaucomatous atrophy
  • Defects in the retinal nerve fiber layer can occur in glaucoma
  • The normal nerve fiber layer appears light colored, somewhat glistening, and elevated (e.g., papillomacular bundle)
  • The retinal nerve fiber layer follows the course of the nerve fiber layer bundles and its loss is most evident in the arcuate bundles
  • Dropout of the nerve fibers appears as a darkened striation or wedge-shaped defect in the bundle

Functional Damage to the Visual System

1.  Associated visual field defects

  • Reduction in retinal sensitivity
  • Constriction of isopters
  • Nasal steps
  • Paracentral scotomas
  • Arcuate scotomas
  • Hemifield asymmetry
  • Temporal changes in visual field patterns 
  • Loss of central acuity

2.  Decreased color vision 

3.  Abnormal visual evoked potential

4.  Abnormal pattern electroretinogram

The main goal in a patient diagnosed as a glaucoma suspect is to accomplish the following:

  • Identify patients at high-risk for developing glaucoma
  • Establish a baseline of clinical findings for future comparative analysis
  • Identify and exclude any oculosystemic conditions associated with open-angle glaucoma
  • Consider medical treatment of high-risk patients to prevent or slow down the development of open-angle glaucoma

To obtain the information required to determine a clinical diagnosis of an open angle glaucoma suspect and prescribe a treatment program, the following service components of a medical eye examination should be performed:

  •  Patient history
  • General medical observation
  • Gross visual field
  • Pupillary examination
  • External ocular examination with biomicroscopy
  • Ophthalmoscopy


Patient History

  • Patients will usually be asymptomatic in the early stages of glaucoma


Intraocular Pressure

  • Measurements above 21 mm Hg
  • Asymmetry above 5 mm Hg

Gross Visual Fields

  • Normal
  • Constrictions

Pupillary Examination

  • A relative afferent pupillary defect (RAPD) may be present if one eye is more affected than the other

External Ocular Examination with Biomicroscopy

  • Normal

Ophthalmoscopic Examination

  • Cup-to-disc ratio > .40/.40
  • Cup-to-disc ratio asymmetry > .20/.20
  • Vertically elongated cup-to-disc ratios 

Patient is a 64-year-old black female with an optic disc appearance that is suspicious for glaucomatous optic atrophy.

  • Cup-to-disc ratio = .75/.70 in the right eye
  • Cup-to-disc ratio = .75/.70 in the left eye
  • Normal neuroretinal rim
  • Normal retinal nerve fiber layer
1a 2a


The following diagnostic tests can provide clincial information in the evaluation of glaucoma and its stage of damage.

Retinal Scanning Laser

  • Can show attenuation of the retinal nerve fiber layer
  • Excavation of the optic disc
3-page-001a Cirrus OCT Scan in a 64-year-old Glaucoma Suspect

Right Eye

  • Large optic cup
  • Moderate cup depth
  • Normal retinal nerve fiber layer thickness
  • Normal TSNIT curve profile

Left Eye

  • Large optic cup
  • Moderate cup depth
  • Normal retinal nerve fiber layer thicknes
  • Normal TSNIT curve profile

Both Eyes

  • No clinically significant asymmetry

Visual Field Examination

Research has shown that over 50% of the nerve fibers in any given retinal nerve fiber layer bundle can be irreversibly damaged before any visual field loss occurs.  Depending upon visual fields to separate those patients with glaucoma from those without the disease would still miss a large number of patients.

For most patients with glaucoma, there appears to be about a five year interval between the loss of enough nerve fibers to create a visual field defect during a visual field examination.  Relying on visual fields alone to diagnose glaucoma could mean delayed treatment for your glaucoma patients and unnecessary loss of visual field in these people.

Visual field defects will depend on the severity of the stage

  • No detectable visual field defect
  • Mild reduction in retinal sensitivity
  • Temporal changes in field patterns

Definite glaucomatous visual field defects

  • Arcuate scotomas
  • Paracentral scotomas
  • Nasal steps
6-page-001a Visual Field Examination Test Results in a 64-year-old Glaucoma Suspect

Right Eye

  • Mild loss of retinal sensitivity
  • Paracentral scotomas in the superonasal quadrant
  • Visual field defects do not correlate with structural evaluation
  • Test results are unreliable
Visual Field Examination Test Results in a 64-year-old Glaucoma Suspect

Left Eye

  • No loss of retinal sensitivity
  • Isolated paracentral scotomas
  • Visual field defects do not correlate with structural evaluation 
  • Test results are reliable


  • Can show abnormal angle structures
  • Abnormal pigmentation of the trabecular meshwork
  • Abnormal anterior chamber anatomy
  • Abnormal iris configuration

Corneal Pachymetry

  • A central corneal thickness of less than 500 microns is a risk factor for glaucoma in the presence of elevated IOPs

Extended Ophthalmoscopy

  • Evaluate optic disc morphology
  • Document structural changes to the optic disc


Fundus Photography

  • To document the progress or lack of progress of glaucoma
  • To document the delivery of medical treatment
  • To document the response to treatment
  • To help plan a treatment program
  • Fundus autofluorescence imaging can be used to detect structural abnormalities and predict functional deficits before standard color fundus photography
  • Multi-spectral imaging with the Annidis RHA System can be used to detect structural abnormalities and predict functional deficits before standard color fundus photography
1b 2b


  • Visual evoked potential testing evaluates the function of the afferent visual sensory system 
  • Electroretinography evaluates the function of the retinal ganglion cells
VEP Test Results in a 64-year-old Glaucoma Suspect

Right Eye

  • Normal waveform shape for both high- and low-contrast responses
  • Normal peak times for both high- and low-contrast responses

Left Eye

  • Normal waveform shape for both high- and low-contrast responses
  • Normal peak times for both high- and low-contrast responses

Both Eyes

  • No clinically significant asymmetry
  • VEP test results correlate with structural evaluation

Serial Tonometry

  • Establish diurnal curve

Ultrasound Biomicroscopy (UBM) and/or Anterior Segment Imaging

  • Determine iris configuration
  • Evaluate anterior chamber anatomy
  • Determine the mechanism of primary glaucoma 
  • Determine the occludability of the angle


  • Measurement of visual acuity
  • Measurement of visual function

Provocative Tests for Glaucoma

  • Risk assessment for angle-closure glaucomas

Open-angle glaucoma suspects are classified based on the number of risk factors present.

  • Low risk — One or two risk factors
  • High risk — Three or more risk factors

Differential diagnosis will depend on if the damage is observed on the optic nerve or a visual field defect is present. Below is a list of possible differential diagnosis.

Optic Nerve Head

  • Congenital and hereditary anomalies of the disc
  • Ischemic optic neuropathy
  • Compressive lesions of the optic nerve

Visual Field Defect

  • Pituitary tumors
  • Ischemic optic neuropathy
  • Vascular disease
  • Drusen of the optic nerve
  • Neurological condition

When initiating treatment, assume that the pre-treatment measurement of intraocular pressure (IOP) is the level that produced damage to the optic nerve.  If the IOP remained at this level, additional damage to the optic nerve would follow.

To treat glaucoma, an IOP level is identified below which further optic nerve damage is unlikely to occur.  This IOP level is the target pressure range and it is selected based on the following:

  • Pre-treatment level of IOP
  • The rapidity with which the damage to the optic nerve occurred, if that is known
  • Patient age
  • General health of the patient

Treatment should maintain the IOP at or below the target level.  The status of the optic nerve, visual fields, electrodiagnostics, and the retinal nerve fiber layer are monitored over time for evidence of stability or deterioration.  In the event of further damage, the target pressure range is reset to a lower level.

Pharmacologic Treatment

Select your initial medication based upon target pressure range, medical history, and ocular history.  If the initial medication fails to achieve the target pressure range within one month, discontinue the initial medication and substitute another.

If the second medication fails to achieve the target pressure, begin combination therapy by using two different medications.  If this strategy fails, you could add still a third class of glaucoma medications to the regimen.  With three different eye drops, non-compliance becomes common and laser surgery may be a better treatment option.

Prostaglandins are the most popular class of medications for glaucoma therapy due to their excellent efficacy, safety index and tolerability.  They flatten the diurnal curve significantly and achieve the greatest IOP reduction of any class of topical medication.

Classes of Glaucoma Medications


  • Lumigan
  • Travatan Z
  • Zioptan
  • Xalatan


  • Timolol
  • Betagan
  • Betimol
  • OptiPranolol

Adrenergic Agonists

  • Alphagan P 0.1% and 0.15%
  • Brimonidine 0.2%
  • Propine

Carbonic Anhydrase Inhibitors

  • Azopt
  • Trusopt

Cholinergic Agonists

  • Pilocarpine
  • Carbachol
  • Echothiophate

Combination Glaucoma Medications

  • Cosopt – carbonic anhydrase inhibitor / beta-blocker
  • Cosopt PF – carbonic anhydrase inhibitor / beta-blocker
  • Combigan – adrenergic agonist / beta-blocker
  • Simbrinza – adrenergic agonist / carbonic anhydrase inhibitor

Changing the Treatment due to Side Effects


  • Red eye
  • Eye color change
  • Excessive eyelash growth
  • Uveitis
  • Macular edema


  • Bronchospasm
  • Pulmonary edema
  • Heart failure
  • Headache
  • Weakness
  • Depression
  • Lethargy
  • Itching
  • Stinging
  • Blurred vision
  • Photophobia
  • Loss of libido

Adrenergic Agonist       

  • Red eye
  • Allergic follicular conjunctivitis
  • Dry mouth
  • Drowsiness

Carbonic Andydrase Inhibitors   

  • Sulfa allergy
  • Red eye
  • Ocular itching
  • Metallic taste
  • Paresthesia of fingers or toes
  • Headache
  • Blood dyscrasias
  • Depression
  • Loss of libido
  • Impotence

Cholinergic Agonists      

  • Red eye
  • Induced myopia
  • Reduced vision in low illumination
  • Headaches
  • Lens opacities
  • Iris cysts
  • Increased risk of angle closure
  • Increased risk of retinal detachment
  • Sweating
  • Salivation
  • Diarrhea
  • Bradycardia
  • Dyspnea


  • Eye color change
  • Stinging
  • Increase in periocular eyelid pigmentation
  • Increase in upper eyelid sulcus deepening

1.  Ventura LM, Golubev I, Feuer W, Porciatti V.  The PERG in Diabetic Glaucoma Suspects With No Evidence of Retinopathy.  J Glaucoma 2010; 19(4): 243-247.
2.  Tsai JC.  VEP Technology for the Detection of Glaucomatous Visual Field Loss.  Glaucoma Today.  2009 March.  Last accessed June 25, 2015.
3.  Banitt M, Ventura L, Feuer W, Savatovsky E, Luna G, Shif O, Bosse B, Porciatti V.  Progressive Loss of Retinal Ganglion Cell Function Precedes Structural Loss by Several Years in Glaucoma Suspects.  National Institutes of Health-National Eye Institute. 7 Feb 2013.  Last accessed June 25, 2015.
4.  Malik R, Swanson W, Garway-Teath D.  The ‘Structure-function’ Relationship in Glaucoma — Past Thinking and Current Concepts.  Clin Experiment Ophthalmol. 2012 May-Jun;40(4):369-80. doi: 10.1111/j.1442-9071.2012.02770.x. Epub 2012 Apr 12. Last accessed June 29, 2015.
5.  Bremmer F.D.  Pupil Assessment in Optic Nerve Disorders.   Eye (Lond). 2004 Nov;18(11):1175-81.  Last accessed June 29, 2015.
6.  Chew S, Cunningham W, Gamble G, Danesh-Meyer H.  Retinal Nerve Fiber Layer Loss in Glaucoma Patients with a Relative Afferent Pupillary Defect.  Invest Ophthalmol Vis Sci. 2010 Oct;51(10):5049-53. doi: 10.1167/iovs.09-4216. Epub 2010 May 5.  Last accessed June 29, 2015.
7.  Tielsch JM, Sommer A, Katz J, Royall RM, Quigley HA, Javitt J.  Racial Variations in the Prevalence of Primary Open-Angle Glaucoma The Baltimore Eye Survey.  JAMA. 1991 Jul 17;266(3):369-74.  Last accessed June 29, 2015.
8.  Rabin J, Gooch J, Ivan D.  Rapid Quantification of Color Vision:  The Cone Contrast Test.  Invest Ophthalmol Vis Sci. 2011 Feb 9;52(2):816-20. doi: 10.1167/iovs.10-6283.  Last accessed June 29, 2015.

Open angle with borderline findings, low risk

Retinal nerve fiber laser scan

Visual field examination

Fundus photography

Extended ophthalmoscopy

Subsequent ophthalmoscopy


Visual evoked potential


Serial tonometry

Anterior segment imaging

Anterior segment ultrasound

Corneal pachymetry

Open angle glaucoma, low risk


The prevalence of open-angle glaucoma is almost 2% of the population over 40 years old.


Glaucoma is not distributed evenly throughout the population.

  • Black Americans 4 to 5 times more likely to develop glaucoma
  • More women than men develop glaucoma
  • Latino Americans have very high risk in advanced age

Risk Factors

  • Vertically elongated cup-to-disc ratios
  • Asymmetric cup-to-disc ratios
  • Intraocular pressures greater than 21 mmHg
  • Advancing age
  • Black or Latino race
  • Thin corneas in the presence of elevated IOPs
  • Family history
  • Medical history