Transcript GR7-13-07

Grand Rounds
Vanderbilt Eye Institute
7/13/07
Ryan Tarantola M.D. PGY-3
Initial Evaluation 6/6/07
CC: Decreased Vision OS
HPI:
• 62 year-old male
• 1 week hx of decreased vision OS
• Initial mild discomfort OS
• Central blind spot OS
PMH: GERD, Hyperlipidemia, Hypotension,
Syncope
POH: Non-Contributory
Allergies: Sulfa
FH: No eye disease
SH: 1ppd x 30 years
Occasional EtOH
ROS: Denies HA, scalp tenderness, muscle
weakness, weight change, jaw
claudication
VA: OD: 20/25
OS: 20/100
Motility: Full OU
Pupils: 32mm OU
Tr RAPD OS
CVF: Central scotoma OS
Ta: OD: 14
OS: 13
Color: OD: 15/15
OS: 10/15
SLE:
External: WNL OU
Lids/Lashes: Clear OU
Conj: White/Quiet OU
Cornea: Clear OU
AC: Deep/Quiet OU
Lens: tr NSC OU
Further Studies?
HVF24-2
Acute onset of unilateral visual loss with
trace RAPD, hyperemic optic nerve, and
central scotoma OS
Differential Diagnosis?
Differential Diagnosis
1. Vascular
a. NAION
b. AAION
c. Papillophlebitis
d. Diabetic Papillopathy
2. Demyelinating
a. Optic Neuritis
3. Toxic
4. Nutritional
5. Hereditary
a. Lebers
6. Infiltrative/Neoplastic
a. Sarcoid
b. Meningioma
c. Lymphoma
7. Infectious
a. TB
b. Syphilis
c. Toxocariasis
d. Toxoplasmosis
e. Syphilis
Additional History/Labs
Patient reports that he has a history of erectile dysfunction and
has used Viagra and Cialis in the past. Most recently he used
Cialis approximately 5 days prior to the onset of his symptoms.
ESR: 27
CRP: 3.4
NAION
• Incidence is 2.3-10.2 per 100,000 in persons > 50 years old
• Males affected in 55% cases
• Peak age range of 55-70 years old
• 95% of cases in Caucasians
NAION
Associations may include:
• Diabetes mellitus (10-25%)
• Hypertension (34-50%)
• Hyperlipidemia
• Migraine
• Smoking
• Hypotensive episode (nocturnal or intraoperative)
• Elevated IOP
• Post cataract extraction/LASIK
• Pro-Thrombotic risk factors
• Sleep apnea
• Optic disc drusen
• Small cup-to-disc ratio
Clinical Characteristics
• Vision loss: Ranges from 20/20-NLP, typically painless (90%)
31-52% > 20/64
34-54% <20/200
• Visual field loss: Altitudinal in 55-80%, mostly inferior
Central scotoma
Arcuate defect
Quadratid defect
Generalized constriction
• Dyschromatopsia
•RAPD
Clinical Characteristics
• Swollen optic disc: 75% diffuse 25% focal
• Hyperemic disc more common than pale disc
• Disc at risk in contralateral eye
• Flame-shaped hemorrhages
• Focal retinal artery narrowing
• Hard exudates: 7%, can form hemi-star or complete star (rare)
Clinical Characteristics
Clinical Characteristics
Fluorescein angiogram, early arteriovenous phase: The temporal portion of the
optic disc fills normally, but the remaining sectors demonstrate markedly delayed
filling.
Clinical Characteristics
IONDT (Ischemic Optic Neuropathy Decompression Trial):
• 38/89 (42.7%) improved 3 or more lines at 6 months
• 40/89 (44.9%) had no or little change
• 11/89 (12.4%) had worsening vision of 3 or more lines
• Recurrence in the same eye is rare 3.6-6.4% over 5 years
• Bilateral disease is extremely uncommon
• Risk of sequential NAION is 15% within 5 years
Optic Nerve Anatomy
•
Intraorbital portion (about 25mm long)
•
Intracanalicular portion (about 9mm long)
•
Intracranial portion (about 16 mm long)
Three zones occur within intraocular optic nerve:
•
prelaminar zone
•
laminar zone
•
retrolaminar zone
Optic Nerve Blood Supply
The ophthalmic artery derives from the top of the internal carotid artery siphon, where it joins up with and occupies an inferior
position to the nerve in the optic canal. In the canal and orbit, the artery gives off several branches that feed the pial circulation. At
8–12mm behind the globe, the ophthalmic artery passes through the nerve sheath and into the nerve, where it runs along the
central aspect of the nerve up to the optic disc; here, it is renamed as the central retinal artery this artery does not contribute
directly to the circulation of the optic nerve head. Instead, blood flow to the optic nerve head derives from the circle of Zinn-Haller,
which receives three major sources of blood: •
Choroidal vessels
•
Four or five short posterior ciliary arteries
•
Small contribution from the pial arterial network
Optic Nerve Blood Supply
Scanning electron photomicrograph of the vasculature of the posterior globe. Superior and inferior
anastomoses from the medial and lateral short posterior ciliary arteries suggest a possible anatomic
correlation for the altitudinal pattern of optic nerve damage often seen in NAION.
Pathophysiology
Most evidence supports insufficient perfusion of retrolaminar nerve head by
short posterior ciliary arteries
Mechanism and location of vasculopathy remains unknown
Possible Mechanisms:
• Altered perfusion of posterior ciliary circulation
• Nocturnal hypotension
• Structural crowding
• Watershed theory
• Autoregulation
Watershed Theory
Fluorescein angiograms showing examples of locations of the watershed zone
in four eyes with anterior ischemic optic neuropathy
Nocturnal Hypotension
Hayreh SS et al. AJO 1994. Nocturnal arterial hypotension and its role in optic
nerve head and ocular ischemic disorders.
• 24-hour ambulatory blood pressure in 166 white patients with AION, NTG, POAG,
and other optic nerve head disorders.
• Significant (P < .0001) decrease in mean systolic (26%) and diastolic (33%) blood
pressure measurements at night.
• Patients with arterial hypertension taking oral hypotensive therapy showed a significant
association between progressive visual field deterioration and nocturnal hypotension,
particularly in anterior ischemic optic neuropathy.
Conclusion: Nocturnal hypotension, in the presence of other vascular risk factors, may
reduce the optic nerve head blood flow below a critical level, and thereby may play a
role in the pathogenesis of anterior ischemic optic neuropathy and glaucomatous
optic neuropathy.
NAION and Erectile Dysfunction Drugs
• Sildenafil (Viagra)
• Vardenafil (Levitra)
• Tadalafil (Cialis)
NAION and Erectile Dysfunction Drugs
Mechanism: Selective inhibitors of cGMP phosphodiesterase type 5 (PDE5)
• Cavernous nerves release NO increased cGMP smooth muscle
relaxation and increased blood flow to corpus cavernosum
• PDE 5 causes cGMP breakdown resulting in decreased blood flow
•Sildenafil has up to 10% inhibitory effect on retinal PDE 6
PDE 5 Inhibitor Ocular Side Effects
Certain:
• Changes in color perception: blue or blue-green tinge
• Blurred vision
• Changes in light perception
• Transient ERG changes
• Conjunctival hyperemia
• Photophobia
Possible:
• Mydriasis
• Retinal vascular accidents
• Subconjunctival hemorrhage
• Ischemic optic neuropathy
NAION and Erectile Dysfunction Drugs
Argument for cause/effect:
Hayreh SS. J Neuro-Ophthalmology 2005:
”The nature of the optic nerve head blood flow and the various factors that influence it,
the systemic vascular effects of these agents, and the clinical features of NAION lead
me to believe that these agents are contributory factors.”
• Cardiovacular risk factors are common in patients using ED drugs
• In reported cases, NAION has occurred soon after drug use
• ED drugs cause systemic hypotension
•Studies showing no change in optic nerve head blood flow with sildenafil may not
be valid
Recommendation: Patients who have CV risk factors, DM, take arterial hypotensive
meds, or have hx of NAION should not take ED drugs.
NAION and Erectile Dysfunction Drugs
Argument against cause/effect:
Fraunfelder et al. J Neuro-Ophthalmology 2005:
• Many reported cases of NAION do not have a temporal association to drug use
• No data to evaluate does response
• De-challenge: clinical course once med is stopped is no different that spontaneous
cases
• Positive re-challenge: single case report
• Plausible mechanism exists, but has not been proven
• Most cases of NAION arise in patients at risk for spontaneous NAION
Recommendation: “The authors believe that the only patients who need to avoid
phosphodiesterase type 5 inhibitors for visual reasons are those who have previously
suffered NAION in 1 eye.”
NAION Treatment
Medical
Prophylactic Measures
• Hyperbaric Oxygen
• Control risk factors
• Corticosteroids
• Minimize nocturnal hypotension
• Aspirin
• Levodopa
• Neuroprotective agents
Surgical
• Optic nerve sheath decompression
• Optic neurotomy
Take Home Points
• NAION is a common cause of unilateral optic nerve dysfunction
• Multiple risk factors suggested to be associated with NAION
• PDE-5 inhibitors may cause increased risk of NAION
• Counsel patients on these medications appropriately
• No effective treatment for NAION has been identified
References
N.J. Newman, R. Scherer and P. Langenberg et al., The fellow eye in NAION: report from the Ischemic Optic
Neuropathy Decompression Trial follow-up study, Am J Ophthalmol 134 (2002), pp. 317–328.
S.S. Hayreh, K.M. Joos, P.A. Podhajsky and C.R. Long, Systemic diseases associated with nonarteritic anterior
ischemic optic neuropathy, Am J Ophthalmol 118 (1994), pp. 766–780.
S.S. Hayreh, Acute ischemic disorders of the optic nerve: pathogenesis, clinical manifestations and management,
Ophthalmol Clin North Am 9 (1996), pp. 407–442.
S.S. Hayreh, M.B. Zimmerman, P. Podhajsky and W.L. Alward, Nocturnal arterial hypotension and its role in optic
nerve head and ocular ischemic disorders, Am J Ophthalmol 117 (1994), pp. 603–624.
R.W. Beck, S.S. Hayreh and P.A. Podhajsky et al., Aspirin therapy in nonarteritic anterior ischemic optic neuropathy,
Am J Ophthalmol 123 (1997), pp. 212–217.
R.A. Egan and F.W. Fraunfelder, Viagra and anterior ischemic optic neuropathy, Arch Ophthalmol 123 (2005), pp. 709–710.
F.W. Fraunfelder, Visual side effects associated with erectile dysfunction agents, Am J Ophthalmol 140 (2005),pp. 723–724.
A.G. Lee and N.J. Newman, Erectile dysfunction drugs and nonarteritic anterior ischemic optic neuropathy,
Am J Ophthalmol 140 (2005), pp. 707–708.
S.S. Hayreh. The blood supply of the optic nerve head and the evaluation of it: myth and reality. Prog Retin Eye Res
2001;20:563-93.
J.E. Grunwald, Siu KK, Jacob SS, et al. Effect of sildenafil citrate (Viagra) on the ocular circulation. Am J Ophthalmol 2001;
131:751-5.
S.S. Hayreh. Erectile dysfunction drugs and non-arteritic anterior ischemic optic neuropathy: is there a cause and effect
relationship? J Neuroophthalmol 2005;25:295-8.