Ron Tongbai, MD

The NY Eye and Ear Infirmary Ophthalmology Grand Rounds

3/16/12

No Relevant Financial Relationships with Commercial Interests

Case Presentation
44 yo Hispanic Male CC: desires 2nd opinion regarding diagnosis of gluacoma by outside ophthalmologist

NYEE, 2011

Case Presentation
HPI: c/o R eye pain which radiates to occiptal area Pohx: none Pmhx: none Meds: none Fhx: no glaucoma ROS: no history of trauma, anemia, loss of blood requiring transfusions

NYEE, 2011

Anterior segment exam

OD VA 20/40 (ph NI) OS 20/30 (ph NI)

IOP
Pupils Motility LLL C/S Corneal A/C Lens Gonio

9
4->3, 2+RAPD Full (no pain) +MGD WNL +arcus senilis d/q Clear CB in all 4 quadrants

10
4->3 Full (no pain) +MGD WNL +arcus senilis d/q clear CB in all 4 quadrants

Pachymeter
ICP

554
0/12

551
12/12

NYEE, 2006

NYEE, 2006

NYEE, 2006

NYEE, 2006

Differential Diagnosis
Significant findings: Normal IOP, +RAPD OD, decreased color vision OD, cup-todisc assymetry with temporal pallor

NYEE, 2006

Differential Diagnosis
Glaucoma Burned out open angle glaucoma POAG with diurnal IOP fluctuations Intermittent angle closure glaucoma Secondary open angle glaucomas (eg. PDS, pseudoexfoliative gluacoma) Thin CCT Normal or low tension glaucoma Disorders of the optic nerve Ischemic optic neuropathy Lebers hereditary optic neuropathy Optic nerve drusen Optic pits Compressive lesions of the optic nerve Systemic disorders Syphilis Tuberculosis Sarcoidosis Multilpe sclerosis Medications Ethambutol Isoniazid

NYEE, 2006

Workup of Cupped Disc with Normal IOP

Thorough history

o o o o o

Systemic medical conditions Medications Family history of glaucoma or normal tension glaucoma History of ocular trauma or surgery Symptoms suggesting elevated IOP from angle closure

Workup of Cupped Disc with Normal IOP

Examination

o o o o o o o o o

BCVA Color vision Pupillary examination Tonometry Pachymetry Gonioscopy Standardized automated perimetry Detailed evaluation of optic nerve and NFL Diurnal IOP curve

Workup of Cupped Disc with Normal IOP

Evaluation of the Optic Nerve

Distinguishing glaucomatous from nonglaucomatous is challenging Generally, optic disc in patients with intracranial compressive lesions is pale and lacks cupping o Many cases published (including Kupersmith et al) describing glaucoma-like cupping of the ON in patients with compressive lesions, and pallor can be lacking (especially early compression) or masked by lenticular changes o Even glaucoma and neuro-ophthalmologists have difficulty distinguishing between glaucomatous and non-glaucomatous cupping
o o

Workup of Cupped Disc with Normal IOP

Additional studies

o o o o o

Disc photos Auscultation and palpation of carotid arteries Exophthalmometry 24-hour blood pressure monitoring Laboratory testing for infectious or inflammatory conditions that can cause optic neuropathy

Workup of Cupped Disc with Normal IOP

Neuroimaging
Neuroimaging and consultation with neuro-ophthalmologist if: o Perimetry suggests damage is further posterior in visual pathway, or atypical visual field defects o ON demonstrates more pallor than cupping o < 65 yo and demonstrates rapid progression of optic nerve damage or marked assymetry of damage between the two optic nerves o Color deficiency o However, deciding who to image remains a significant challenge o Reportedly, 8% of patients diagnosed with NTG have associated compressive lesions of the anterior visual pathways o Compression of the intracranial optic nerve or the anterior chiasm can produce arcuate visual field defects resembling glaucoma with sparing of central vision- study found 6.5% of patients with NTG with glaucomatous like VF changes had compression of ON o Highly specific, but low sensitivity o Age younger than 50 years - sensitivity: 46.4% o Optic nerve pallor in excess of cupping - sensitivity: 45.5% o Vertically aligned visual field defects sensitivity: 47.7%
o

Workup of Cupped Disc with Normal IOP

Neuroimaging
o

Some groups advocate performing a careful evaluation of the total clinical picture initially and maintaining a high index of suspicion during follow-up

MRI

NYEE, 2011

MRI shows small old infarct in the right superficial cerebellar hemisphere (I am working on obtaining the images from BI, should have it in a few days)

Diurnal curve
OD 7:00 AM 10 OS 10

9:00 AM
11:00 AM 1:00 PM 3:00 PM 5:00 PM

12
10 10 9 10

12
12 11 10 11

Labs

CBC o WBC: 6.03 o HGB: 14.9 o HCT: 45.1 o PLT: 237 o SMA12: WNL o RPR: Nonreactive o MHA-TP: neg o ESR: 3 o ACE: 17 o ANA: <1:40 o TSH 1.2
o

Normal tension glaucoma:

Epidemiology and Etiology
Characterized by glaucomatous optic neuropathy in patients with IOP consistently < 21 mm Hg Diagnosis of exclusion Beavers Dam Eye Study reported nearly 1/3rd of glaucoma patients can be classified as NTG 2/3rds of Japanese patients with glaucoma Etiology: unclear Contributing factors: Vasospastic events Hypoperfusion Nocturnal hypotension Hypercoagulability Increased blood viscosity Genetic factors Low diastolic BP associated with glaucomatous VF progression- Okumara et al, 2012 Associations with migraine HAs, Raynauds phenomenon, diffuse cerebral ischemia, various autoimmune disorders

Normal tension glaucoma:

Distinguishing from POAG

Visual field defects typically steeper, deeper, closer to fixation VF defects typically greater than predicted based on ON NYEE, 2011 appearance More localized defects of the RNFL

Normal tension glaucoma:

Disc hemorrhage
Greater propensity for disc hemorrhages Worrisome sign of poorly controlled glaucoma, likely to experience progressive VF loss in 17-20 months 8.2% patients with DH have VF progression (3.6% without DH) Predicts damage to contralateral eye

NYEE, 2011

Normal tension glaucoma:

Treatment
Identify and treat comorbid medical conditions: anemia, arrythmias, hypothyroidism, autoimmune disease, migraines Collaborative Normal Tension Glaucoma Study Lowering IOP by 30% or more reduced rate of VF loss Rate of progression without treatment is variable and usually slow since half of untreated patients showed no progression in 5 years Factors that increase rate of progression: female gender, migraines, presence of disc hemorrhages Pharmacologic treatment Topical agents: prostaglandin analogs, alpha2-agonists, CAI, miotics Beta-blockers are controversial, thought to decrease perfusion Alpha2-agonists thought to have additional neuroprotective effects on optic nerve- no conclusive evidence available Calcium channel blockers useful Memantine Surgical treatment ALT if medications are ineffective, poor compliance Filtration surgery Target IOP: IOP at which no further structural or functional disease progression is observed

Normal tension glaucoma:

Low-Pressure Glaucoma Treatment Study

Randomized, double-masked, multicenter clinical trial comparing brimonidine and timolol in preserving visual function in NTG Statistically fewer brimonidine-treated patients had visual field progression than timolol-treated patients (9.1% vs 39.2%, P=.001) More brimonidine-treated than timolol-treated (28.3% vs 11.4%) patients discontinued study participation because of drug-related adverse events (P=.008) Mean treated IOP was similar for brimonidine- and timolol-treated patients at all time points

Patient follow-up:

Patient was followed for the next 10 years VF stable over 10 years (VFs are being scanned in, I will have them ready in the next few days) IOPS have been stable over the 10 years ON appearance similar to disc photos, no progression

Patient follow-up:
IOP over 10 years
20 18 16 14 12

Alphagan P started

IOP

10 8 6 4 2 0 Jan-99

OD OS

Jan-00

Jan-01

Jan-02

Jan-03

Jan-04

Jan-05

Jan-06

Jan-07

Jan-08

Jan-09

Jan-10

Jan-11

Jan-12

Time

References
1. Okumura Y, Yuki K, Tsubota K. Low Diastolic Blood Pressure Is Associated with the Progression of NormalTension Glaucoma. Ophthalmologica. 2012 Feb 25. 2. Krupin T, Liebmann JM, Greenfield DS, Ritch R, Gardiner S; Low-Pressure Glaucoma Study Group. A randomized trial of brimonidine versus timolol in preserving visual function: results from the Low-Pressure Glaucoma Treatment Study. Am J Ophthalmol. 2011 Apr;151(4):671-81. Epub 2011 Jan 22. 3. Stein JD and Challa P. Diagnosis and Treatment of Normal-Tension Glaucoma. EyeNet. 2007. American Academy of Ophthalmology Web Site. 4. Kupersmith MJ, Krohn D. Cupping of the optic disc with compressive lesions of the anterior visual pathway. Ann Ophthalmol 1984;16:948-53.

5. Nikhil S Choudhari1, Aditya Neog1, Vimal Fudnawala2, Ronnie George3. Cupped disc with normal intraocular pressure: The long road to avoid misdiagnosis. Indian Journal of Ophthalmology. 2011;59.6:491-497.

Thank you!
Dr. Teng Dr. Kupersmith Dr. Huang

Learning objectives
After completing this activity, the learner should have improved his/her ability to: Identify differential diagnosis for Normal Tension Glaucoma Describe the signs, symptoms, workup, pathophysiology, management, and prognosis for Normal Tension Glaucoma

Questions
1. Which one of the following is false A. MEWDS more commonly affects females B. MEWDS is predominantly a unilateral disease C. MEWDS has an excellent prognosis D. A systemic workup is often necessary when someone presents with MEWDS E. None of the above
Answer: D 2. UHR-OCT suggests that MEWDS is a disease primarily of the A. Inner retina B. Outer retina C. Choroid D. Vitreous E. None of the above Answer: B