Normal-Tension Glaucoma; Abnormal Macular OCT Scan

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

Case Report

• 72-year-old black woman presented with a complaint of decreased vision
• Case history described a subjective decrease in vision in the right eye
• The patient had been examined by another eye doctor six months earlier, received new eyeglasses, and wanted to see if another new pair of eyeglasses would improve her vision

Conclusion

Glaucoma is a diagnosis of exclusion.  In particular, the diagnosis of normal-tension glaucoma can be difficult.  To avoid missing the diagnosis, remember that “normal” intraocular pressure relates to the statistical sense and is no guarantee that the patient does not glaucoma. 

Additionally, caution should be exercised in making the diagnosis of normal-tension glaucoma without multiple recordings of intraocular pressure several times during the day.  Intraocular pressure can vary dramatically during the twenty-four hour daily cycle, from day-to-day, and when influenced by environmental factors.  As thorough an understanding of a patient’s intraocular pressure is essential before beginning any treatment regimen. 

History of Present Illness

Associated Symptoms:  decreased vision was more bothersome when reading
Location:  right eye
Duration:  2 months
Quality:  vision is dim
Context:  constant
Severity:  moderate decrease in vision
Timing:  getting worse
Modifiers:  none, trying to see if new eyeglasses will help

Review of Systems

The patient reported that she was in good health for her age.

• Past history:  non-contributory
• Family history:  non-contributory
• Social history:  quit smoking ten years earlier

Best Corrected Distance Visual Acuity

• 20/25 in the right eye
• 20/20 in the left eye

Normal Examination Findings

• Mental status
• Intraocular pressure
• Gross medical observation
• Basic sensorimotor examination
• External examination
• Adnexal examination
• External ocular examination with biomicroscopy

Intraocular Pressure Measurements

• 16 mm Hg in the right eye @ 5:00 pm
• 16 mm Hg in the left eye @ 5:00 pm

Gross Visual Fields

• A constriction in the superior field of the right eye revealed with confrontation testing

Pupillary Examination

Pupillary reactivity testing using a RAPDx automated pupillographer was abnormal.

• A relative afferent pupillary defect was detected in the right eye
• Index of defect number was 0.81 for the amplitude of the pupillary response in the right eye 
• Numbers is calculated by determining the log of the difference in amplitude between the pupillary responses
• Numbers above 0.30 are considered abnormal
• Higher the number, the more likely pathology is present in the neural light reflex pathway

Ophthalmoscopy

The evaluation of the retina and the optic nerve was abnormal.

• Cup-to-disc ratio = .75/.80 in the right eye
• Cup-to-disc ratio = .70/.65 in the left eye 
• Peripapillary atrophy in both eyes

Clinical Diagnosis

The clinical diagnosis is determined based on the knowledge obtained fro the patient’s medical history and from the results of the eye examination alone, without the benefit of diagnostic tests or procedures.

The patient’s clinical disgnosis is normal-tension open-angle glaucoma based on the following clinical findings:

• Optic neuropathy in the right eye 
• Relative afferent pupillary defect in the right eye
• Visual field defect in the right eye

Treatment Plan

To gather the clinical information required to treat normal-tension open-angle glaucoma, a diagnostic and treatment program is initiated.  

• Determination of different types of diagnoses
• Selection of one or more treatment options

After a clinical diagnosis has been determined, the diagnostic process continues with a process that involves the identification and exclusion of differential diagnoses.  The differential diagnosis process allows the eye doctor to distinguish between two or more diseases with similar signs and symptoms by systematically comparing their signs and symptoms. 

Differential Diagnoses

Much like glaucoma, the first differential diagnosis that needs to be determined in this patient is showing any glaucomatous optic neuropathy versus some other retinal or neurological disease.  The list of possible differential diseases would include: 

• Retinal detachment
• Pituitary tumors and other neurological conditions
• Ischemic optic neuropathy
• Vascular disease
• Drusen of the optic disc
• Congenital disc anomalies

• Retinal nerve fiber layer scan
• Visual field examination
• Gonioscopy
• Fundus photography
• Visual evoked potential
• Electroretinography
• Serial tonometry

The decision to order and perform additional testing is totally based on the concept of medical necessity which can only be determined by the examining optometrist or ophthalmologist.

After a clinical diagnosis has been determined, the diagnostic process continues with a process that involves the identification and exclusion of differential diagnoses.  The differential diagnosis process allows the eye doctor to distinguish between two or more diseases with similar signs and symptoms by systematically comparing their signs and symptoms. 

Differential Diagnoses

The first differential that needs to be determined in this patient is glaucoma vs. some other retinal or neurologic disease.  The list of possible diseases would include any pathology that produces an asymmetric partial optic atrophy and a relative afferent pupillary defect in the same eye.

The following diseases share some of the clinical signs and symptoms of glaucoma: 

• Retinal detachment
• Pituitary tumors and other neurological conditions
• Ischemic optic neuropathy
• Vascular disease
• Drusen of the optic disc
• Congenital disc anomalies 

• Retinal nerve fiber layer scan
• Visual field examination
• Gonioscopy
• Fundus photography
• Visual evoked potential
• Electroretinography
• Serial tonometry

The decision to order and perform additional testing is totally based on the concept of medical necessity which can only be determined by the examining optometrist or ophthalmologist.

INITIAL EXAMINATION – DAY 1

Refraction

• Measuring visual acuity is a method of evaluating functional vision loss
• Advanced glaucoma can produce central visual field defects which result in a loss of visual acuity 

Retinal Laser Scan — Nerve Fiber Layer 

• Measuring the average retinal nerve fiber layer thickness provides an overall assessment of retinal health
• The procedure can be accomplished by using the Cirrus OCT manufactured by Carl Zeiss Meditec

Retinal Laser Scan — Macula

		Right Eye Moderate overall loss of the retinal nerve fiber layer in the papillomacular bundle Clinical presentation is known as “splaying of the fovea” and is characterized by a flattening of the macular thickness scan Fovea “opens up” and the foveal pit looks bigger Condition usually caused by low-tension glaucoma or vascular compromise
Left Eye Normal macular structure Red spot in the center of the fovea is not clinically significant

Visual Field Examination

Automated threshold perimeters characterize specific parameters of the overall visual field status by the use of numbers called Global Indices.  One of the indices, Mean Deviation (MD), expresses the raw data generated by the instrument.

A visual field defect can be classified as mild, moderate or advanced based upon an abnormal Mean Deviation.

• Mild visual field defect = 0 through -5.99 dB
• Moderate visual field defect = -6.00 dB through -11.99 dB
• Advanced visual field defect = anything above -12.00 dB 

Right Eye

• Severe loss of retinal sensitivity
• Incomplete superior arcuate scotoma
• Enlarged blind spot
• Marginal test reliability
• Visual field defect appears to be a horizontal and vertical respect of the midline

Left Eye

• Mild loss of retinal sensitivity
• Incomplete superior arcuate scotoma
• Normal blind spot
• Good test reliability

Both Eyes

• Asymmetric loss of retinal sensitivity

Because of the apparent respect of the midline, the etiology of the visual field defect in the right eye could be neurologic in origin.  As a result, an MRI of the brain with contrast was ordered.

SUBSEQUENT ENCOUNTER — DAY 14

Magnetic Resonance Imaging (MRI)

One day after the eye examination, an MRI without and with intravenous gadolinium was performed at a nearby imaging center.  There was no prior examination for comparison.  

Radiologist’s Findings:

• There is no restricted diffusion to suggest recent infarction
• There is no intracranial mass effect or midline shift
• The ventricular system, sulci, and cisterns are normal in size and morphology
• No brain parenchymal signal abnormality or abnormal enhancement is demonstrated
• No orbital mass or optic nerve enhancement is demonstrated
• Sinuses and mastoids are clear
• There are scattered T2 hyperintensities in the supratentorial white matter and brainstem

Radiologist’s Impression:

• No acute intracranial abnormality
• No enhancing mass lesion or recent infarct
• T2 hyperintensities are most compatible with chronic small vessel ischemia, particularly given the patient’s age

Physical Diagnosis

A lesion of the lateral geniculate nucleus near the sulcus could produce the visual field defect seen in the right eye, but it should have been revealed on the MRI examination.  Because of this, the differential diagnosis of neurologic disease was excluded and the clinical diagnosis of normal-tension glaucoma was confirmed.

Visual Field Examination

A 60-4 testing strategy sometimes gives a different perspective compared to traditional 30-2 field examinations.

Right Eye

• Superior arcuate scotoma
• Good test reliability

Left Eye

• Superior arcuate scotoma
• Good test reliability
  

Both Eyes

• Clinically significant asymmetry correlates with abnormal OCT test results, abnormal RAPDx automated pupillography and decreased visual acuity in the right eye

Visual Evoked Potential Testing

The VEP is an objective electric sign of visual pathway function and its parameters are sensitive to abnormalities in the visual system.  By measuring the speed and strength of the neural responses along the visual pathway, VEP testing evaluates the integrity of the afferent visual sensory system.

• Abnormal waveform peak latencies and shape helps to identify pathologies ranging from the eye through the brain to the primary visual cortex
• The procedure can be accomplished with the NOVA-LX VEP Testing Device manufactured by DIOPSYS

Measuring the conduction speed and magnitude of the neural response from the eye to the cortex can be helpful in assessing early changes in glaucoma.  Although not diagnostic of glaucoma, abnormal VEP test results in addition to other abnormal clinical findings can assist in making the difficult diagnosis of early glaucomatous damage. 

All of the diagnostic test results confirmed the clinical diagnosis of normal-tension open-angle glaucoma, although this diagnosis may change with additional trending of intraocular pressure.  Additional diagnostic tests for glaucoma such as serial tonometry, provocative glaucoma testing, gonioscopy or extended ophthalmoscopy were not considered medically necessary on this patient’s last two visits.  Photographic documentation of the optic nerve would be an additional medically necessary test that could be obtained at any follow-up examination.

According to Current Procedural Terminology, when eye doctors perform ophthalmological examinations, the complexity of medical decision-making is not separated from the examining techniques used.  As a guideline to assist eye doctors in enhancing their medical decision-making skills, consider that the complexity of medical decision-making involves three components. 

The first component concerns the number of possible diagnoses and treatment options that must be considered. Modern glaucoma diagnosis involves the determination of structural damage to the eye and/or functional loss to the visual system.  Once these assessments are made, the glaucoma must be classified by type and ICD-9 lists multiple designations of glaucoma suspect (ICD-10 includes many more).  The most specific diagnosis in this case would be 365.12, low-tension glaucoma.

The second component concerns the amount and complexity of medical records and diagnostic tests that have to be obtained, reviewed and analyzed.  In addition to an eye examination, this visit required the review and analysis of a subjective refraction, a retinal laser scan and a threshold visual field examination.  In addition, an MRI of the brain was ordered for the next day.  Also, orders were entered into the medical record to perform a confirmatory visual field examination and visual evoked potential testing at the next visit.

Third, the complexity of medical decision-making is affected by the risk of significant complications and/or morbidity associated with mild glaucoma and the risks involved in any treatment options.  This patient’s glaucoma was classified as a significant problem where the risk of total vision loss without treatment was possible.  In addition, because the treatment plan would involve chronic pharmaceutical treatment with the potential for ocular and systemic side effects, the pharmacology complications had to be considered when deciding on the initial treatment options.

Treatment Guidelines

To begin the treatment of glaucoma, intraocular pressure must be lowered and an initial target pressure range must be established.  A general guideline is to base the initial pressure range on the category of damage to the visual system.

• Mild damage needs a 20-30% reduction in pre-treatment IOP as the initial target pressure range
• Moderate damage needs a 30-40% reduction in pre-treatment IOP as the initial target pressure range
• Advanced damage needs a 40-50% reduction in pre-treatment IOP as the initial target pressure range

Doctors should always remember that the goal of glaucoma therapy is to prevent additional or future vision loss, not achieve some arbitrary target therapy range.

Due to the advanced glaucomatous damage to the right eye, a 40-50% reduction in the pre-treatment intraocular pressure was selected as the initial target pressure range.

Treatment Program

Modern glaucoma therapy generally utilizes prostaglandins as the primary therapy.  The first goal of treating glaucoma is to achieve the lowest possible IOP on a single agent and prostaglandins generally have the greatest efficacy of all glaucoma medications.

Monotherapy with prostaglandins improves patient compliance, may decrease costs, and improves the safety profile and tolerability of using topical medications.  These drugs reduce intraocular pressure by increasing uveoscleral outflow. IOP reduction averages almost 30% with some patients showing even greater response but a small percentage showing minimal to no response.

Monotherapy with combination medications such as Combigan (Allergan, Inc.) is another primary therapy.

Avoiding medicolegal liability if complications arise is an important part of modern ophthalmic practice.  This avoidance is best accomplished by making sure that you have obtained the patient’s informed consent to treat their glaucoma. Once you have made the patient fully aware that using topical glaucoma medicine involves the risks of side effects, you can proceed with the treatment plan.

After obtaining the patient’s informed consent to treat her glaucoma, Combigan ophthalmic solution was prescribed 1 drop twice daily in both eyes.

A target pressure range of 8-10 mm Hg was established for each eye.

Next visit scheduled for three weeks.

Discussion

This case demonstrates several key aspects of treating a patient with an initial diagnosis of normal-tension open-angle glaucoma.  On initial examination, the damage to the optic disc and the loss of visual field was advanced in both eyes. The glaucomatous damage in the right eye’s visual system was more advanced and the intraocular pressure was never measured above 16 mm Hg in either eye.

• First, no additional or second opinions are required.  Even thought there was advanced damage in the right eye, there was no ocular emergency and no need for a referral to a glaucoma sub-specialist at this time.
• Second, this patient’s clinical history supports the modern understanding of the pathophysiology of glaucoma. We know that glaucoma is an optic neuropathy.  Structural damage to the retinal nerve fiber layer is usually the first milestone in the natural history of glaucoma.  The loss of retinal nerve fibers is closely followed by changes in the appearance of the optic disc.
• Third, functional loss, which is documented by abnormal visual field testing, abnormal visual evoked potential testing, abnormal pupil reactivity, abnormal color vision or loss of visual acuity, usually occurs later in the natural history of the disease.  This case demonstrates that the patient’s glaucoma could have been easily missed without the benefit of automated pupillography.
• Fourth, even though elevated intraocular pressure is a risk factor for glaucoma, we must always be mindful that the glaucomas are a family of diseases characterized by optic neuropathy – not elevated intraocular pressure.

Baltimore Eye Study

• This patient was examined by another eye doctor in another practice six months earlier.

The findings from the Baltimore Eye Study are still true.  One of the findings from the Baltimore Eye Study is that glaucoma can be hard to diagnose.  The study revealed that 50% of all people found to have glaucoma during the study had seen an eye doctor within the past year and were unaware that they had glaucoma.  This failure to diagnose glaucoma is most explained by a function of concentrating on intraocular pressure as a diagnostic indicator as opposed to the appearance of the optic disc.  

Early Manifest Glaucoma Trial

Regarding intraocular pressures as a diagnostic indicator, the Early Manifest Glaucoma Trial demonstrated that there is considerable variability of the intraocular pressures in patients with glaucoma.  The study also determined that 20-35% of glaucoma patients do not have elevated intraocular pressures.  In this group of patients, the intraocular pressure will consistently measure below 21 mm Hg.  In addition, the study demonstrated that 50% of patients with glaucoma – even if they had elevated intraocular pressures most of the time – had screening intraocular pressures below 22 mm Hg.

SUBSEQUENT ENCOUNTER — DAY 7