Grand RoundsVanderbilt 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: 32mm 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. Vasculara. NAIONb. AAIONc. Papillophlebitisd. Diabetic Papillopathy

2. Demyelinatinga. Optic Neuritis

3. Toxic

4. Nutritional

5. Hereditarya. Lebers

6. Infiltrative/Neoplastica. Sarcoidb. Meningiomac. Lymphoma

7. Infectiousa. TBb. Syphilisc. Toxocariasisd. Toxoplasmosise. 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

• 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

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

• 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

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

  •   

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 Anatomy

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.

Optic Nerve Blood Supply

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.

• Sildenafil (Viagra)

• Vardenafil (Levitra)

• Tadalafil (Cialis)

NAION and Erectile Dysfunction Drugs

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

• Hyperbaric Oxygen

• Corticosteroids

• Aspirin

• Levodopa

• Neuroprotective agents

Surgical

• Optic nerve sheath decompression

• Optic neurotomy

Prophylactic Measures

• Control risk factors

• Minimize nocturnal hypotension

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

ReferencesN.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.