Ron Tongbai, MD

The NY Eye and Ear InfirmaryOphthalmology 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

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

 Anterior segment exam

OD OS

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

IOP 9 10

Pupils 4->3, 2+RAPD 4->3

Motility Full (no pain) Full (no pain)

LLL +MGD +MGD

C/S WNL WNL

Corneal +arcus senilis +arcus senilis

A/C d/q d/q

Lens Clear clear

Gonio CB in all 4 quadrants CB in all 4 quadrants

Pachymeter 554 551

ICP 0/12 12/12

NYEE, 2006

NYEE, 2006

NYEE, 2006

NYEE, 2006

 Differential Diagnosis

NYEE, 2006

Significant findings: Normal IOP, +RAPD OD, decreased color vision OD, cup-to-disc assymetry with temporal pallor

 Differential Diagnosis

NYEE, 2006

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• Leber’s hereditary optic neuropathy• Optic nerve drusen• Optic pits• Compressive lesions of the optic nerve

Systemic disorders• Syphilis• Tuberculosis• Sarcoidosis• Multilpe sclerosis

Medications• Ethambutol• Isoniazid

 

o Systemic medical conditions o Medicationso Family history of glaucoma or normal tension glaucomao History of ocular trauma or surgeryo Symptoms suggesting elevated IOP from angle closure

Workup of Cupped Disc with Normal IOPThorough history

 

o BCVAo Color visiono Pupillary examinationo Tonometryo Pachymetryo Gonioscopyo Standardized automated perimetryo Detailed evaluation of optic nerve and NFLo Diurnal IOP curve

Workup of Cupped Disc with Normal IOPExamination

 

o Distinguishing glaucomatous from nonglaucomatous is challenging o Generally, optic disc in patients with intracranial compressive lesions

is pale and lacks cuppingo 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

Workup of Cupped Disc with Normal IOPEvaluation of the Optic Nerve

 

o Disc photoso Auscultation and palpation of carotid arterieso Exophthalmometryo 24-hour blood pressure monitoringo Laboratory testing for infectious or inflammatory conditions that can

cause optic neuropathy

Workup of Cupped Disc with Normal IOPAdditional studies

 

o Neuroimaging and consultation with neuro-ophthalmologist if:o Perimetry suggests damage is further posterior in visual

pathway, or atypical visual field defectso ON demonstrates more pallor than cuppingo < 65 yo and demonstrates rapid progression of optic nerve

damage or marked assymetry of damage between the two optic nerves

o Color deficiencyo 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%

Workup of Cupped Disc with Normal IOPNeuroimaging

 Workup of Cupped Disc with Normal IOPNeuroimaging

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

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)

NYEE, 2011

 Diurnal curve

OD OS

7:00 AM 10 10

9:00 AM 12 12

11:00 AM 10 12

1:00 PM 10 11

3:00 PM 9 10

5:00 PM 10 11

 Labs

o CBCo WBC: 6.03o HGB: 14.9o HCT: 45.1o PLT: 237

o SMA12: WNLo RPR: Nonreactiveo MHA-TP: nego ESR: 3o ACE: 17o ANA: <1:40o TSH 1.2

 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, Raynaud’s 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

appearance More localized defects of the RNFL

NYEE, 2011

 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

 

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Patient follow-up:IOP over 10 years

Time

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Alphagan P started

References1. Okumura Y, Yuki K, Tsubota K. Low Diastolic Blood Pressure Is Associated with the Progression of Normal-

Tension 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. TengDr. KupersmithDr. 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 falseA. MEWDS more commonly affects femalesB. MEWDS is predominantly a unilateral diseaseC. MEWDS has an excellent prognosisD. A systemic workup is often necessary when someone presents with MEWDSE. None of the above

Answer: D

2. UHR-OCT suggests that MEWDS is a disease primarily of the…A. Inner retinaB. Outer retinaC. ChoroidD. VitreousE. None of the above

Answer: B