H40.1211-1233 Low-Tension Glaucoma

Normal-Tension Glaucoma A chronic, progressive optic neuropathy characterized by morphologic changes at the optic nerve and retinal nerve fiber layer Occurs in the presence of statistically normal intraocular pressure measurements Open drainage angles, no apparent resistance to aqueous outflow Affects 20% to 35% of all glaucoma patients Intraocular pressure is within the “statistically normal” range and under 21 mmHg

Glaucomatous Optic Atrophy

• Changes in coloration of the optic nerve
• Enlargement of the optic cup
• Wipe out of the neuroretinal rim
• Fallout of the retinal nerve fiber layer

For patients with normal-tension glaucoma, 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.

Because of this, understanding normal-tension glaucoma from an oculosystemic perspective is best when deciding on treatment options that allow for neuro-protection of the optic nerve.  Despite the etiology, normal-tension glaucoma has the same milestones of development as other types of open-angle glaucoma.

Normal-Tension Glaucoma vs Primary Open-Angle Glaucoma

• Sharper field loss in normal-tension glaucoma
• Shallower cupping in normal-tension glaucoma
• Larger overall disc area in normal-tension glaucoma
• Disc hemorrhages five-fold more prevalent in normal-tension glaucoma than primary open-angle glaucoma
• Higher and greater incidence of peripapillary atrophy and crescents in normal-tension glaucoma than primary open-angle glaucoma

Structural Damage to the Eye

• Atrophy of the optic nerve
• Acquired loss of retinal ganglion cells 

		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
		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
		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
		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
		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
		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

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

Electrodiagnostic abnormalities

• Delayed peak times
• Reduced amplitudes
• Abnormal waveform morphology

Color vision abnormalities

• Acquired color vision defects

Pupillary reactivity abnormalities

• Relative afferent pupillary defect

The main goal in a patient with normal-tension glaucoma is to accomplish the following:

• Make a clinical diagnosis of normal-tension glaucoma
• Identify and exclude any oculosystemic conditions associated with normal-tension glaucoma

Patient History

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

Intraocular Pressure

• Never measures above 21 mmHg

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

• Asymmetric optic disc cupping
  • cup-to-disc ratio = .50/.40 in the right eye
  • cup-to-disc ratio = .60/.60 in the left eye
• Inferior and superior focal optic disc notch in the left eye 
• Pallor of the temporal neuroretinal rim in the left eye 

Is the cupping physiologic or pathologic?

• Accurate visual fields as well as other optic nerve function and structure studies should identify truly diseased nerves
• Misdiagnosis of megalopapillae

Is the cupping progressive?

• Serial or sequential optic nerve function and structure studies will identify progression.  There are a host of masquerading conditions that present with field defects (e.g., filted discs) that are non-progressive.  Do not spend a lot of time trying to treat a non-progressive anomaly.

DIAGNOSTIC TESTS

Fundus Photography

Medical Evaluation

• Vascular studies
• Blood glucose
• CBC (Hyperviscosity/ anemia)
• B12
• ANA
• ACE
• CXR
• FTA-ABS/ RPR
• Lyme
• Thyroid
• Mitochondrial DNA
• SPEP retinal antibodies
• Serum chemistries (lipids)
• ESR (erythrocyte sedimentation rate)
• Carotid blood flow studies
• Neuroimaging (if under age 65, rapidly progressing, unilateral, dyschromatopsia, acuity loss) of the orbits and chiasm

Be patient in making a diagnosis of normal-tension glaucoma.  It should take at least 6-12 months in order to make the diagnosis when determining progression.

Normal-tension glaucoma is an acquired open-angle glaucoma.  The disease can be classified by its Level of Control and its Category of Damage.

Levels of Glaucoma Control

Good Control

• Achievement of an intraocular pressure at or below the target pressure without significant adverse effects.  Susequent observation confirms appropriateness of target pressure level by documenting lack of significant glaucomatous progression.

Borderline Control

• Achievement of an intraocular pressure near but higher than the target pressure, judged capable of inducing further glaucomatous damage. 

Uncontrolled

• Intraocular pressure above the target pressure, judged capable of causing significant progressive glaucomatous damage
• Any evidence of glaucoma progression
• Optic disc hemorrhage
• Reliable, reproducible, significant progression of visual field defects
• Progressive enlargement of the optic cup
• Progressive observable loss of the retinal nerve fiber layer
• Symptomatic decline in vision, consistent with glaucoma progression, otherwise unexplainable in a patient with moderate to advanced glaucoma

Category of Glaucoma Damage

Mild Damage — Visual Field

• No deteclable visual field defect
• Mild generalized reduction in retinal sensitivity
• Mild constriction of isopter
• Nasal step to 20 degrees
• Paracentral scotomas

Mild Damage — Optic Nerve

• No definite pathologic cupping
• Symmetric or vertically elongated cup enlargement
• Intact neuroretinal rim
• Previously observed optic disc hemorrhage

Moderate Damage — Visual Field

• Moderate generalized reduction in retinal sensitivity
• Moderate constriction of isopters, absolute defects within 9 degrees of fixation

Moderate Damage — Optic Nerve

• Enlarged optic cup
• Changes in coloration of the neuroretinal rim
• Sloped neuroretinal rim
• Focal optic disc notch
• Prominent lamina cribrosa

Advanced Damage — Visual Field

• Severe reduction in retinal sensitivity
• Severe constriction of isopters, absolute defects within 3 degrees of fixation
• Loss of central acuity
• Temporal island

Advanced Damage — Optic Nerve

• Diffuse enlargement of the optic cup
• Wipe out of all or a portion of the neuroretinal rim

Normal-tension glaucoma is a diagnosis of exclusion.  If the doctor investigates thoroughly, most cases of normal-tension glaucoma can be correctly ascribed to another disease.

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
• Optic nerve hypoplasia
• Tilted discs

Visual Field Defect 

• Pituitary tumors
• Ischemic optic neuropathy
• Hypovolemic optic neuropathy
• Non-glaucomatous optic neuropathy
• Arteritic and non-arteritic anterior ischemic optic neuropathy
• Burnt-out primary open-angle glaucoma
• Vascular disease
• Chronic angle-closure glaucoma
• Drusen of the optic nerve
• Intraocular pressure-lowering systemic medications, such as beta blockers for hypertension
• Abnormally thin cornea masking true ocular hypertension
• 70 um change in corneal thickness can approximate 5 mm Hg of intraocular pressure
• 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 eyedrops, 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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