Download Gadani, Priyal

Priyal Gadani, O.D.
Residents Day 2009 Submission
Abstract:
This report will present an atypical case of suspected normal tension glaucoma. Information will be
presented on differentiating between normal tension glaucoma and preexisting toxic optic neuropathy.
I.
Case History –
a. Patient demographics: 56 year old African American Male
b. Chief Complaint: Patient referred for glaucoma evaluation, secondary to large C/D ratio OU,
family history, and race
c. Ocular, Medical History: (+) Bell’s Palsy (left side of face), (+) Hypertension, (+) Heart
Disease, (+) CVA 9-10 months ago, (+) Exposure Keratopathy OS secondary to Bell’s Palsy,
lower lid ectropion OS, and lagophthalmos OS.
d. Medications: Vicodin, Enalapril, Aspirin
e. Other salient information: The patient had been seen one week prior for a comprehensive
eye exam. The patient was referred to the glaucoma clinic for a baseline glaucoma
evaluation secondary to large C/D ratio OU, positive family history, and race as the primary
risk factors. The referring doctor wanted to obtain further testing on the patient to
differentiate between previously undiagnosed normal tension glaucoma versus optic
neuropathy from another cause. At the initial visit on July 23, 2009, the C/D ratio was noted
in the right eye as 0.80(H)/0.85(V) with pallor noted, and in the left eye as 0.70(H)/0.70(V).
The patient’s BCVA was 20/30- in the right eye and 20/40+ in the left eye. IOP at the initial
visit was 10 mm Hg OD, OS by Goldmann applanation tonometry at 10:28 AM. No afferent
papillary defect (APD) was noted in either eye.
II.
Pertinent Findings:
Glaucoma Evaluation (July 27, 2009)
a. Family Ocular History: (+) glaucoma – mother (on Xalatan and one other unknown drop)
b. Clinical Findings
i. Distance Best Corrected Visual Acuity (BCVA)/Subjective Refraction:
1. OD +0.25-0.75x042 Distance VA 20/25+2
2. OS plano-1.00x070 Distance VA 20/40 (pin hole no improvement)
ii. Pupils equal, round, reactive to light, no APD
iii. EOMS: full range of motion OD, OS
iv. Slit Lamp Examination (SLE):
1. Lids/Lashes: lower lid ectropion and lagophthalmos OS
2. Conjunctiva: trace injection OD, 2+ injection nasal bulbar conjunctiva OS
3. Cornea: clear OD, 2+ to 3+ SPK/keratitis with NAFL staining centrally
4. A/C: deep and quiet OU
5. Iris: flat and intact OU
6. Lens: 2+ nuclear sclerosis OU
7. Vitreous: clear OU
v. IOP
1. OD: 15 mm Hg, OS: 8 mm Hg at 3:35 PM by Goldmann applanation
vi. Dilated Fundus Examination (DFE) (poor view of left eye secondary to exposure
keratitis)
1. C/D: OD: 0.9(V)/0.85(H), OS: 0.7(V)/0.7(H), laminar dots visible OU
2. NR Rim: no temporal rim OD, temporal rim thinning OS, no disc
hemorrhages OU, margins distinct OU
3. Vessels: attenuated OU
4. Macula: flat OU
5. Periphery: no holes, breaks, or tears 360 degrees OU
c. Physical
i. None
d. Laboratory Studies:
i. None
e. Radiology Studies:
i. None
Priyal Gadani, O.D.
Residents Day 2009 Submission
f.
Other Tests:
i. Pachymetry: OD 515 microns, OS 470 microns
ii. HVF 24-2 Sita Standard: OD: superior arcuate defect, denser superior temporally,
defects also present inferior nasally; OS: scattered defects in no specific pattern (no
clusters), overall depression in sensitivity OS most likely due to exposure keratitis OS
iii. GDx: NFI: 80 (OD), 42 (OS); OD: Significant RNFL drop out superiorly and inferiorly,
overall flattening of TSNIT curve; OS: Mild RNFL drop out inferiorly, poor Q score OS
iv. OCT: unable to obtain due to poor fixation by patient
v. Flat fundus photos: obtained but poor quality
At this baseline glaucoma evaluation in July 2009, the patient was questioned in more detail
about his previous ocular history. He remarked that he had been treated with Vitamin B12 for
his eyes “going color blind” in 2001 or 2002, and that it seemed to help restore his color
vision. He was then asked if he had a history of heavy smoking or drinking, to which he
replied that he had been a heavy smoker and drinker for about 20 years from the 1970s to
1990s.
After the glaucoma examination, we were able to obtain records from his eye examinations in
1995 and 2003. A review of his past records revealed that he had previously been referred
for a neuro-ophthalmology evaluation in 1995 and was treated for “possible early toxic
neuropathy OS>OD” secondary to a gradual decrease in visual acuity over the past six
months, distortions in his inferior visual field, central scotoma on Humphrey visual field testing
and Amsler Grid testing, with a history of heavy alcohol and tobacco consumption. The
patient also subjectively described seeing out of his left eye a red spot with a blue halo
around it for the six months prior to this visit.
Pertinent Exam Findings from neuro-ophthalmology evaluation in 1995:
 BCVA: OD 20/20, OS 20/25+1
 Pupils: no afferent pupillary defect
 IOP: OD 13 mm Hg, OS 6 mm Hg at 2:25 PM by Goldmann applanation
 C/D ratio: OD 0.45/0.45, OS 0.5/0.5, margins distinct OU, no pallor noted OU, rim
tissue well perfused OU
 Macula: even pigmentation OU
 Ishihara and D-15 color testing: failed OS
 HVF 24-2 and 10-2 – central scotoma OU
At the conclusion of the neuro-ophthalmological examination in 1995, the patient was started
on treatment with “Berocca Plus” tablets, which are composed of B group vitamins, vitamin C,
magnesium, calcium, and zinc. The patient was educated to take one tablet once daily by
mouth (prescribed 100 tablets). In the neuro-ophthalmologist’s dictation, Leber’s neuropathy
was ruled out because of the patient’s “good visual acuity, negative family history, and
absence of peripapillary telangiectasias.” The following blood tests were ordered at this visit
to rule out pernicious anemia or lead/thallium toxicity: complete CBC, serum B-12, blood
lead, and blood thallium (heavy metal panel) to exclude a toxic source because of the
patient’s occupation. However, the patient’s blood test results were not included in the
records that were obtained, and there is no record that the original treatment plan had been
altered after obtaining the test results. The patient then appears to have been lost to followup until 2003 when the patient returned for a comprehensive eye examination. Therefore, it
is difficult to determine how fast his visual acuity and central scotoma improved after
beginning vitamin supplementation, assuming he was compliant with the recommended
treatment.
Comprehensive eye exam pertinent findings from February 2003:
 BCVA: OD 20/25+1, OS 20/30
 Pupils: no afferent pupillary defect
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Priyal Gadani, O.D.
Residents Day 2009 Submission
 IOP: OD: 19 mm Hg, OS 19 mm Hg at 10:10 AM by Goldmann applanation
 C/D ratio: 0.8/0.8 OD and 0.7/0.7 OS
In 2003, based on the findings, the assessment again was to rule out possible optic
neuropathy versus glaucoma (based on the large C/D ratio OU). The patient was asked to
return for a baseline glaucoma evaluation, which is summarized below.
Glaucoma evaluation pertinent findings from March 2003:
 BCVA: OD: 20/25+1, OS 20/20-2
 Pupils: No afferent pupillary defect
 IOP: OD: 14 mm Hg, OS: 15 mm Hg at 10:15 AM by Goldmann applanation
 Pachymetry: OD 541 microns, OS 546 microns
 C/D Ratio: OD: 0.75/0.7, OS: 0.65/0.65, temporal thinning OU
 Fundus/stereo photos taken
 HVF 24-2 Sita Fast: OD field shows paracentral defects (GHT outside normal limits),
OS shows scattered isolated defects in no particular pattern.
 GDx: NFI 49 (OD), 23 (OS); OD: inferior > superior RNFL thinning with overall
depression of TSNIT curve, OS: superior temporal RNFL thinning
At the time, no conclusions could be made based on the findings. It was noted that it was
unknown whether the findings were a result of glaucomatous changes versus preexisting
optic neuropathy. The patient was educated to return in six months to repeat glaucoma
testing and assess if there had been any progressive visual acuity or field loss, but the
patient was lost to follow-up again until 2009.
III.
Differential Diagnosis
a. Primary/leading: normal tension glaucoma versus previous toxic optic neuropathy secondary
to alcohol/tobacco consumption
b. Other metabolic/nutritional optic neuropathies (vitamin B12 deficiency, pernicious anemia,
radiation-related, ethambutol, isoniazid)
c. Leber’s hereditary optic neuropathy
d. Retrobulbar mass lesion
e. Previous anterior ischemic optic neuropathy
f. Previous acute blood loss or shock causing infarction of the optic nerve head
IV.
Diagnosis
a. Based on the findings from the July 2009 glaucoma evaluation and after reviewing the
patient’s records from 1995 and 2003, the patient’s assessment was normal tension
glaucoma OU versus other preexisting optic neuropathy OU.
b. The patient had many risk factors for normal tension glaucoma: increased C/D ratio > 0.6,
C/D asymmetry > 0.1, IOP asymmetry > 4, positive family history, race, age, thin central
corneal thickness (OU), thinning of superior and inferior RNFL on GDx (OU), thin rim OU, and
vascular disease (HTN).
c. Based on progressive RNFL thinning OU and HVF loss OD compared to previous GDx and
HVF testing from 1995 and 2003, the findings were suggestive of normal tension glaucoma,
and it was thought that the benefits of IOP lowering outweighed the risks.
d. In my opinion, the patient likely has some residual effects from the previous history of toxic
optic neuropathy with concurrent normal tension glaucoma that has developed over time.
V.
Discussion
a. Normal Tension Glaucoma
i. Normal tension glaucoma (NTG) constitutes a major differential diagnosis of toxic
optic neuropathy. Glaucoma can result in a chronic optic neuropathy that some
research indicates can be worsened by nutritional deficits. As in the case of our
patient, it can be difficult to distinguish between glaucoma with normal IOP and
toxic optic neuropathy. However, an increase in cup/disc ratio and specific visual
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Priyal Gadani, O.D.
Residents Day 2009 Submission
field patterns are characteristic of glaucomatous neuropathy and allow one to
make the distinction between glaucoma and other optic neuropathies.
ii. Normal tension glaucoma can present with normal or decreased visual acuity,
normal intraocular pressure, cupping of the optic nerve (large cup relative to field
loss), splinter hemorrhages at the disc margin, and visual field loss close to
fixation. NTG is more prevalent in women, in those having vasospastic disorders
including migraine, Raynaud’s phenomenon, ischemic vascular disease,
autoimmune disease, and coagulopathies. It is also associated with a history of
poor perfusion of the optic nerve from arteriosclerosis, hypotension, shock,
myocardial infarction, or massive hemorrhage.
b. Toxic Optic Neuropathy
i. Toxic or nutritional optic neuropathy, also known as tobacco-alcohol amblyopia,
most commonly affects individuals with a history of heavy drinking and tobacco
consumption. Those affected lack protein and B vitamins in their diet, and most
of their caloric intake has been from alcohol. However, in individuals with
tobacco amblyopia, particularly those with a history of pipe smoking, patients
may have good nutrition, but still present with visual impairment. Some
individuals may also present with coexisting pernicious anemia or deficiency in
vitamin B12 absorption.
ii. Toxic optic neuropathy usually presents with progressive, bilateral, and
symmetrical vision loss, central scotoma, and dyschromatopsia in the red-green
axis. The decrease in visual acuity may be mild to severe, ranging from acuities
from 20/20 to worse than 20/400. Since the neuropathy is usually bilateral and
symmetric, an afferent pupillary defect is uncommon, but an APD has been
present in some asymmetric cases. On dilated fundus examination, the optic
discs may appear normal or may show subtle temporal pallor. Some cases have
also presented with splinter disc hemorrhages, disc hyperemia, or disc edema.
On visual field testing, most patients show a bilateral, central or ceco-central
scotoma. Optic atrophy may result over time with loss of the nerve fiber layer in
the papillo-macular bundle. Patients may also demonstrate an abnormal visual
evoked response.
iii. The pathophysiology of toxic optic neuropathy involves the biochemical pathways
in cell energy production and the reduction of free radicals. In tobacco
amblyopia, the toxic factor is the production of cyanide. In experimental models,
chronic exposure to high levels of cyanide results in demyelination.
VI.
Treatment
a. Treatment of our patient:
A monocular trial of Travatan-Z 1 gt qhs OD was initiated (to allow for healing of left eye
exposure keratopathy). The right eye also showed more RNFL thinning and HVF loss compared
to the left eye, and the IOP in the right eye was higher than the left eye’s. The patient was
scheduled to return in one month for an IOP check and D-15 testing.
b. Response to Treatment:
The patient returned on August 31, 2009 for a one month IOP check. IOP was 10 mm
Hg OD and 12 mm Hg OS at 3:15 pm by Goldmann applanation. The patient seemed to respond
well to treatment in the right eye, so Travatan-Z was started in the left eye as well. D-15 color
testing was also performed at this visit, which confirmed the presence of a deutan defect in both
eyes, consistent with the D-15 findings from 2003. The patient is scheduled to see a glaucoma
specialist on October 13, 2009 for further evaluation to determine if glaucoma treatment should
be continued.
VII.
Management
a. Normal Tension Glaucoma
i. Patients who are suspected to suffer from NTG should have the following workup: slit lamp examination, tonometry, gonioscopy, ophthalmoscopy, and corneal
pachymetry. Visual fields should be tested every four to six months. One should
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Priyal Gadani, O.D.
Residents Day 2009 Submission
also consider testing the diurnal curve (IOP measurement q2h for 10-24 hours)
and tonography. Patients with questionable NTG or atypical cases should also
be evaluated for other causes of optic neuropathy. Additional testing that can be
performed includes the following: cardiovascular work-up, blood pressure
monitoring, carotid auscultation, ECG, CBC (to check for anemia), ESR,
cholesterol and triglycerides, and blood sugar levels. Lastly, a neurological
examination can be requested to rule out possible optic nerve compression by
tumor (diagnosis by exclusion).
ii. The Collaborative Normal Tension Glaucoma Study showed evidence that IOP
lowering by 30% or more influenced the course of normal tension glaucoma,
showing a “slower rate of incident visual field loss.” Thus, for patients with
numerous risk factors, it is important to begin therapy with topical IOP-lowering
medication to slow progression in visual field loss.
b. Toxic Optic Neuropathy
i. Evaluation of patients with suspected toxic optic neuropathies includes obtaining
a complete history with particular attention to ocular symptoms, ocular and
neurological examination including: color vision, pupils, motility, Hertel
exophthalmometry, and ophthalmoscopy. Visual fields should be tested. A head
and orbital CT scan or MRI can be obtained to rule out intracranial mass lesions.
The following lab tests should be obtained to rule out pernicious anemia and
vitamin B deficiencies: CBC, vitamin B1, B2, B6, and B12 levels.
ii. In most cases, treatment of toxic optic neuropathy involves weekly injections of
1000 units of hydroxocobalamin administered for ten weeks. Patients are also
advised to take multivitamins as well as to eat a well-balanced diet. Education
on drinking and smoking cessation should also be provided.
iii. A complete medical and neurological evaluation is necessary for those patients
who exhibit systemic manifestations of nutritional deficiencies.
iv. The prognosis for most patients with toxic optic neuropathy is relatively good if
treatment is obtained early and the patient is compliant. Visual recovery may be
slow. Permanent visual loss secondary to optic atrophy may occur in advanced
cases or those unresponsive to treatment.
VIII.
Conclusion/Clinical Pearls
a. Patients may sometimes present with a syndrome of central or ceco-central scotoma,
reduction in visual acuity, and dyschromatopsia. In addition to normal tension glaucoma,
these patients should be evaluated for toxic or nutritional causes for their visual impairment.
b. Nutritional deficiencies should be considered and appropriate lab testing acquired to
differentiate between toxic, nutritional, and hereditary causes. Nutritional vitamin
supplementation can be used for treatment in combination with smoking cessation and
abstinence from alcohol use.
c. Normal tension glaucoma must be differentiated from other optic neuropathies by examining
change in cup to disc ratio and retinal nerve fiber layer drop out over time. If progression
appears to exist, one must weigh the benefits and risks of IOP lowering and begin treatment
if indicated.
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Priyal Gadani, O.D.
Residents Day 2009 Submission
IX.
Bibliography/Literature Review
1. Anderson, Douglas R. Collaborative Normal Tension Glaucoma Study. Current Opinion in
Ophthalmology. 2003; Volume 14: pp. 86-90
2. Aung, T., K. Okada, D. Poinoosawmy, et al. The phenotype of normal tension glaucoma patients with
and without OPA1 polymorphisms. Br J Ophthalmology 2003 87: pp. 149-152.
3. Behbehani, R., R C Sergott, and P J Savino. Tobacco-alcohol amblyopia: a maculopathy?. British
Journal of Ophthalmology. 2005 November; 89(11): pp. 1543–1544.
4. Gill, G.V. and D.R. Bell, Persisting nutritional neuropathy amongst former war prisoners, J Neurol
Neurosurg Psychiatry 45 (10) (1982), pp. 861–865.
5. Hsu, Cynthia, Neil R. Miller. Optic Neuropathy from Folic Acid Deficiency without Alcohol Abuse.
Ophthalmologica 2002; 216: pp. 65-67.
6. Kaiser, Peter, and Neil Friedman. The Massachusetts Eye and Ear Infirmary Illustrated Manual of
Ophthalmology. 2nd ed. Philadelphia: Saunders, 2004. pp. 434-435.
7. Kanski, Jack J. Clinical Ophthalmology. 6th edition. Edinburgh: Butterworth Heinemann, 2007, p. 799.
8. Kerrison, J.B., N.R. Miller, F. Hsu, T.H. Beaty, I.H. Maumenee and K.H. Smith et al., A case-control
study of tobacco and alcohol consumption in Leber hereditary optic neuropathy, Am J Ophthalmol
130 (2000), pp. 803–812.
9. Orssaud C., O. Roche, J.L. Dufier. Nutritional Optic Neuropathies. Journal of the Neurological
Sciences. 2007 November; Volume 262, Issues 1-2: pp. 158-164.
10. Phillips PH. Toxic and deficiency optic neuropathies; In: Miller NR, Newman NJ (eds): Walsh and
Hoyt’s Clinical Neuro-Ophthalmology, 6th edition, Volume 1. Philadelphia, Lippincott Williams &
Wilkins, 2005: pp. 447-463.
11. Woon, Cybele, Rosa Tang, Gabriel Pardo. Nutrition and Optic Nerve Disease. Seminars in
Ophthalmology, Vol. 10, No. 3, 1995: pp. 195-202
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