H40.1111-1133 Primary Open-Angle Glaucoma

Retinal Nerve Fiber Layer (RNFL)

• The retinal nerve fiber layer contains all the ganglion cells
• The structure has a striated appearance traversing across the major blood vessels and it can be seen with an ophthalmoscope
• Loss of vision from glaucoma is the result of axonal damage at the level of the optic disc and retinal ganglion cell axons follow an arcuate path to the optic disc
• Axons from the temporal retina curve around the macular area area, while neurons from the temporal superior and inferior retinal areas stay apart and respect the horizontal raphe

Functional Damage to the Eye

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 

Decreased of color vison

• Acquired loss of blue/yellow color discrimination

Visual evoked potential abnormalities on waveforms:

• Delayed P100 peak time is the usual finding in patients with glaucoma
• Decreased P100 amplitude may be found in patients with glaucoma
• Wave shape perturbation may be found in patients with glaucoma

Electroretinography abnormalities on waveforms generated by the NOVA-ERG testing device manufactured by DIOPSYS:

• Three unequally spaced sinusoidal-like wave peaks
• Magnitude of the pERG response below 1.2 microvolts
• Magnitude D value is less than half the value of the Magnitude

The main goal of the diagnostic evaluation in a patient with glaucoma is to accomplish the following:

1.  Determine the Presence of Glaucoma

2.  Classify the Type of Glaucoma:

• Elevated-tension glaucoma
• Normal-tension glaucoma
• Angle-closure glaucoma
• Glaucoma associated with other disorders and/or conditions

3.  Assess the Amount of Glaucomatous Damage to the Visual System:

• Mild damage
• Moderate damage
• Advanced damage

4.  Establish a Target Pressure Range

5.  Prescribe a Treatment Program:

• Topical medication
• Laser surgery
• Oral medication
• Implant surgery
• Filter surgery

6.  Monitor bi-weekly until target achieved

7.  Assess some or all of the following in six months:

• Optic nerve
• Intraocular pressure
• Visual fields
• Electrodiagnostics
• Color vision
• Retinal nerve fiber layer
• Visual acuity

Patient History

Patients will usually be asymptomatic in the early stages of glaucoma.  If the patient is complaining of a loss of visual field or visual acuity, the glaucoma is in an advanced stage of its progression.

Intraocular Pressure

Abnormal clinical signs include intraocular pressure in any of the following presentations:

• IOP above 22 mm Hg as measured by applanation tonometry
• Measurements above 24 mm Hg are clinically significant
• 99.85% of the population have IOPs below 24 mm Hg
• Increase in IOP over time
• Asymmetric > 5 mm Hg
• Diurnal variation > 6 mm Hg

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

Abnormal clinical signs in the anterior chamber that are associated with glaucoma:

Retinal Scanning Laser

• Can show attenuation of the retinal nerve fiber layer
• Excavation of the optic disc

Gonioscopy

• 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

Electrodiagnostics

• Visual evoked potential testing evaluates the function of the afferent visual sensory system 
• Electroretinography evaluates the function of the retinal ganglion cells

Extended Color Vision Examination

Dyschromatopsia of Glaucoma

New studies suggest that acquired color vision defects are common in glaucoma.  Most color vision defects associated with glaucoma are a blue-yellow type and in some patients, glaucoma-induced loss of color discrimination may precede glaucoma-induced visual field loss.  In diseases like glaucoma, the fact that color vision may be affected while visual acuity is preserved suggests that chromatic mechanisms may be more susceptible to damage than those of light sensitivity in some patients.

The prevalence of acquired color vision defects in glaucoma is as follows:

• Blue-yellow deficiency is found in 30% – 50% of patients
• General loss of chromatic discrimination affects 20% – 30%
• Red-green deficiency is seen in 5% of patients
• 20% – 40% of patients with glaucoma never develop chromatic defects
• Some patients develop them in only the advanced stages of the disease

Screening tests devised to diagnose genetic red-green color defects like Ishihara pseudoisochromatic plates cannot be used alone to diagnose patients with a loss of color vision caused by an eye disease like glaucoma.  If you are relying on pseudoisochromatic plates as your primary screening mechanism, you could add an auxiliary color vision tests such as Sahlgren’s Saturation Test or the Velhagen-Brosch-mann plates that concentrates on the bluish-green to purple color region to cover the full spectrum.

Although popular with some doctors, the Farnsworth D-15 test excludes the most important part of the color circle if your are looking for glaucoma-induced blue-yellow defects.  Alternatively, the Farnsworth D-100 is somewhat time-consuming and does not illuminate saturation deficits.

Current best practices involves testing for the dyschromatopsia of glaucoma with Konan Medical’s ColorDx software.The Extended Adult Adaptive Evaluation is the best testing strategy for diagnosing acquired color vision deficiencies.The extended evaluation consists of five sections and is adaptive based upon the results of the General Section.

General Section:  26 test plates for genetic color vision deficiencies
Tritan Section:  12 test plates for acquired deficiencies 

If parts of the General Section are missed, the Conditional Sections below are added to the testing strategy:

Protan Section:  Extended test for quantification of Protan (red) deficiencies
Deutan Section:  Extended test for quantification of Deutan (green) deficiencies
Farnsworth D-15:  Extended synergistic test for alternate evaluation methods 

Ultrasound Biomicroscopy (UBM) and/or Anterior Segment Imaging

• Determine iris configuration
• Evaluate anterior chamber anatomy

Serial Tonometry

• Establish diurnal curve 

Refraction

• Measurement of visual acuity
• Measurement of visual function

Provocative Tests for Glaucoma

• Risk assessment for angle-closure glaucomas

Glaucoma may be congenital or acquired and it can be further sub-classified into open-angle or angle-closure types based on anterior chamber anatomy.  Most patients have one of the acquired forms of the disease, and the open-angle glaucomas are the most common type. 

Open-angle glaucomas can be sub-classified into normal tension or elevated tension types based on intraocular pressure.  Elevated tension glaucomas can be further sub-classified into primary or secondary types based on the presence or absence of associated factors contributing to the elevated intraocular pressure.

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

Prostaglandins

• Lumigan
• Travatan Z
• Zioptan
• Xalatan

Beta-Blockers

• 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

Docosanoids

• Rescula

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

Prostaglandins

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

Beta-Blockers

• 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

Docosanoids

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

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