Retina Imaging Conference Brett Mueller, D.O., Ph.D. 9/10/2015 University of Louisville Department of Ophthalmology and Visual Sciences

Patient Presentation CC: Decreased Vision Right Eye CC: Decreased Vision Right Eye HPI: HPI: 38 yo WM presents w/ blurry vision OD for one week. Pt states it happened suddenly w/out pain. Pt denies any history of trauma or straining. Of note, the patient is an avid weightlifter that uses supplements including ephedera (dietary supplement containing ephedrine and pseudoephedrine).

History POHx: none PMHx: Hypertension w/ most recent PCP visit being 178/81. He stated he is not taking any blood pressure medications at this time. FAMHx: none ROS: none MEDS: none ALLERGIES: none

Exam VA TP P 20/80+1 (+1.25 sph) 20/ no RAPD EOM: full OU CVF: full OU 3→2

Exam OD OS LIDS/LASHES WNL WNL CONJ WNL WNL CORNEA WNL WNL IRIS WNL WNL LENS WNL WNL

Fundus Photos OD photo demonstrates pre-retinal and intraretinal hemorrhages extending along the arcades and in the macula OD OS

FAF Photos OD OS OD photo demonstrates pre-retinal and intraretinal hemorrhages extending along the arcades and in the macula

1.Macula is flat with no evidence of CME. 2.Pre-retinal, sub-ILM blood demonstrated through the retinal hemorrhages. 1.OD 2.OD

FA Arterial Phase 00:13:00 Early AV Phase 00:20:00 Early arterial phase shows good arterial filling w/ no ischemic retinal areas. Early AV phase demonstrates venous laminar filling.

FA AV Phase 00:30:00 AV Phase 00:40:00 Both AV phase photos at 30 and 40 seconds demonstrate delayed filling of the venous circulation w/ prolonged laminar flow.

Labs WBC: 5.2 (4.5-10) Hemoglobin: 14.6 ( ) Hematocrit: 44.2 ( ) Platelets: 250 ( ) Fibrinogen: 236 ( ) PT: 13.6 ( ) PTT: 27.2 ( )

Labs Protein C: 86 (70-180) Protein S: 123 (70-150) Antiphospholipid antibody: Anticardiolipin, Beta-2 glycoprotein, antiphospholipid antibody and lupus anticoagulation: negative Factor V Leiden: negative

Summary DDx:  Non-ischemic Central Retinal Vein Occlusion  Valsalva Retinopathy PLAN: OBSERVATION with 1 month f/u 38 y/o WM with decreased vision OD. Examination and FA reveal multiple pre-retinal and intraretinal hemorrhages with delayed venous filling. Patient has a history of weight lifting and supplement consumption that contain ephedrine and pseudophedrine.

Exam 1 month later VA TP P 20/CF 2ft (+1.25 sph) 20/ no RAPD EOM: full OU 4→2 SC

1 month later ODOS OCT: OD demonstrates serous neurosensory retinal detachment

Central Retinal Vein Occlusion  Disease of the arterial circulation  Divided into non-ischemic and ischemic disease  Mechanism of action: Thrombosis of the central retinal vein at or posterior to the level of the lamina cribrosa.

 Age (90% greater than 50), systemic arterial hypertension, open-angle glaucoma, diabetes mellitus and hyperlipidemia.  Oral contraceptives and diuretics have also been associated as risk factors for the development of CRVO Risk Factors for Central Retina Vein Occlusion

 Rare predisposing hypercoagulable conditions associated with this disease include:  Hyperhomocysteinemia  Protein S deficiency  Protein C deficiency  Disorders associated with vasculitis like sarcoidosis and lupus. Risk Factors for Central Retina Vein Occlusion

Central Retinal Vein Occlusion Evaluation and Management  Determination should be made if the patient has non-ischemic or ischemic CRVO.  Absence of treatment, patients with CRVO should be monitored monthly for the first 6 month for the development of anterior segment neovascularization.  Most common complications include vitreous hemorrhage, anterior segment neovascularization, and neovascular glaucoma.

Central Retinal Vein Occlusion Treatment  CRUISE (Study of the Efficacy and Safety of Ranibizumab Injection in Patients With Macular Edema Secondary to CRVO)  Phase III Multicenter, randomized, controlled clinical trial 392 eyes with CRVO and secondary macular edema (>250μm), BCVA of 20/40 to 20/320  3 groups: Sham injection Ranibizumab (Lucentis) 0.3mg Ranibizumab 0.5mg

Central Retinal Vein Occlusion Treatment  CRUISE (Study of the Efficacy and Safety of Ranibizumab Injection in Patients With Macular Edema Secondary to CRVO)  Results: At month 6, BCVA gains of >15 ETDRS letters in 46.2% of patients receiving 0.3 mg, 47.7% of those receiving 0.5 mg, and 16.9% of those receiving sham injections.  GALILEO and COPERNICUS  Demonstrated similar effects but with aflibercept.

Central Retinal Vein Occlusion in the Young  Anomalous retinal anatomy at the level of the optic nerve  Hyperviscosity syndromes caused by autoimmune diseases or cancers (usually bilateral)  Antiphospholipid syndrome, increased homocysteine, Factor C/S def.  Malignant hypertension w/ CRF

 Case report identifying 2 healthy, athletic young patients (< 40 yo) that developed a CRVO and had a negative hypercoagulation workup.  Both patients had complete resolution of their ME and returned to 20/20 vision after getting 3 monthly intravitreal injections of Avastin. Moisseiev E, Sagiv O, Lazar M. Intense exercise causing central retinal vein occlusion in a young patient: case report and review of the literature. Case Rep Ophthalmol Apr 5;5(1): doi: / eCollection 2014 Jan. PubMed PMID: ; PubMed Central PMCID: PMC

 Studied 55 patients younger than 56 years of age (mean age 44) to investigate whether hypercoagulability plays a role in the thrombus formation in patients with a CRVO.  Results  27% of patients had one positive test result suggesting hypercoagulability.  4 patients had elevated homocysteine levels  2 patients had a Factor V Leiden mutation  3 patients had protein S deficiency.  3 patients had + lupus anticoagulant  3 patients had + anticardiolipin antibodies Lahey JM, Tunç M, Kearney J, Modlinski B, Koo H, Johnson RN, Tanaka S. Laboratory evaluation of hypercoagulable states in patients with central retinal vein occlusion who are less than 56 years of age. Ophthalmology Jan;109(1): PubMed PMID:

THANK YOU

References 1. Retina and Vitreous, BSCS 2. Moisseiev E, Sagiv O, Lazar M. Intense exercise causing central retinal vein occlusion in a young patient: case report and review of the literature. Case Rep Ophthalmol Apr 5;5(1): doi: / eCollection 2014 Jan. PubMed PMID: ; PubMed Central PMCID: PMC Lahey JM, Tunç M, Kearney J, Modlinski B, Koo H, Johnson RN, Tanaka S. Laboratory evaluation of hypercoagulable states in patients with central retinal vein occlusion who are less than 56 years of age. Ophthalmology Jan;109(1): PubMed PMID: Kanski’s Clinical Ophthalmology A systemic Approach, Eighth Edition. Brad Bowling 5. Gass JDM. Stereoscopic Atlas of Macular Diseases: Diagnosis and Treatment, 4th ed. St. Louis, Mosby, Barry C, Singh J, Constable IJ. Are optic disc drusen exhibiting Autofluorescence, pseudofluorescence or reflectance? Journal of Ophthalmic Photography 22:32-35, Thach AB, Yau L, Hoang C, Tuomi L. Time to clinically significant visual acuity gains after ranibizumab treatment for retinal vein occlusion: BRAVO and CRUISE trials. Ophthalmology May;121(5): doi: /j.ophtha Epub 2014 Jan Kavoussi SC, Kempton JE, Huang JJ. Central retinal vein occlusion resulting from anomalous retinal vascular anatomy in a 24-year-old man. Clin Ophthalmol May 20;9: doi: /OPTH.S eCollection PubMed PMID: ; PubMed Central PMCID: PMC