1. John Koziarski, MD Family Surgical Veins Battle Creek, MI

2. I will be discussing the off-label use of medications

3. 2005 25 Year old Female 6 yr history of pain, heaviness, aching since pregnancy 6 years prior No significant PMH No hx of migraines

4. Ultrasound Exam Bilat GSV reflux Bilat SSV refluv Incompetent Cockett perforator right leg Bilat deep system insufficiency

5. Treatment Surgical Sclerotherapy Thermal ablation bilat GSV and bilat SSV Ligation incompetent Cockett perforator Multiple sessions with 0.66% Polidocanol liquid

6. 2009 Over the previous 1 yr Ultrasound Increasing pain and aching and swelling left leg despite compression stockings 5-6 mm reticular veins over thighs, 2-3 mm varicosities legs No evidence of bilat GSV of bilat SSS No neovascularity or refluxing acc veins 3 incompetent perforators left thigh/leg Bilat deep system reflux

7. Treatment Chemoablation Perf Sclerotherapy Superficial Varicosites 3 perforators left thigh/leg treated 0.5 ml of 2% STS/ CO2 foam (1:4) Perivenous injection of NS to compress vein Perforators closed No complications

8. Jan 2010 Treatment of superficial varicosities Left thigh 2 ml 0.2% liquid STS 4 ml 0.4% STS/CO2 foam (1:4) Stocking applied Pt went to work (in another physician’s office)

9. 30 min post injection 60 min post injection Called office c/o blurred vision left eye Reassured that visual disturbances can happen and should resolve. Said she would lie down for a while at work. Called office again Still blurred vision left eye Now pain in right eye (10/10) and blurred vision rt eye Nausea BP 90/60 HR 70 SaO2 97%

10. To ER Chief Complaint Diagnostic Work Up Blurred vision left eye resolved Still had pain IN her rt eye and decreased vision Headache Chest pain/pressure Nausea No focal neurologic deficit EKG Troponin CXR MRI Brain MRA/MRV brain All Normal

11. ER Disposition Treated Discharged Dilaudid Zofran Imitrex No real improvement in pain, but nausea improved Vicodin, Zofran F/U Family Dr in am

12. 24 hours post injection Family Physician Ophthamologist Main complaint right eye pain and vision loss Some chest pain/pressure Did not “seem” like a migraine Later- CT scan chest- No PE Vision right- 20/100 left- 20/20 Retina normal IOP normal Rt cornea “ground glass” appearance Ischemic?

13. Right Eye Left Eye

14. Cornea

15. Treatment Eye patch Drops 6 Weeks Cornea Healed Visual acuity normal Some light sensitivity

16. Further Workup Transthoracic Echo Small PFO TEE with bubble study No PFO TCD with bubble study No PFO

17. Further Workup Neurologist Hypercoagulable w/u Negative Repeat MRI (Jun 2010) Normal Repeat MRI (Dec 2010) Normal

18. Frequency of Visual Disturbances (VD) after Foam Sclerotherapy of 1.4% Could be “positive” or “negative” or both 50% headache Other Sx included nausea, photophobia, chest pressure, and parathesias. 18/20 pts with sx had Diffusion-Weighted MRI All were normal. 5 had Non specific White Matter lesions

19. Hypothesizes that endothelin-1, released from the treated vessel endothelium, may be the mediator VD can occur with liquid or foam, though more frequent with foam (Guex et al Dermatol Surg 2005) Endothelin-1 has been associated with retinal vasospasm, migraine with aura, and bronchconstriction

20. Cornea No blood supply Receives O2 and nutrients from tears and aqueous humor Endothelin-1 has been found in the Epithelium and tears (Lu et al.Exp Biol Med 2001) Effects on Cornea are not well understood. May effect cell growth and apoptosis, and may promote corneal healing. (Salvatore, et al. J of Ophth 2010)

21. Summary 30 yr old female, no history of migraine, underwent foam sclerotherapy of reticular veins with 4 ml of 0.4% STS/CO2 foam and 2 ml 0.2% STS liquid Experienced what seemed to be “typical” visual disturbances, but with the addition of corneal injury Etiology is unclear