RESOLUTION OF REFRACTORY CYSTOID MACULAR EDEMA OF BIRDSHOT CHORIORETINOPATHY WITH TOCILIZUMAB AND AFLIBERCEPT CASE REPORT Mónica Martínez Díaz, José Gregorio García García Enrique Júdez Navarro, Virginia Bautista Ruescas

INTRODUCTION Birdshot chorioretinopathy (BCR) is a bilateral, autoinmune posterior uveítis with a distinct clinical phenotype and a strong association with HLA-A29. The HLA-A*29.02 subtype is strongly associated with BCR ( 95% of patients) The disease is chronic, often progressive and has significant potential for irreversible tissue damage and visual loss. It is a rare cause of uveítis. The actual prevalence is uncertain but is likely to be less tan 1 per 100.000, posible in the range 0.1-0.6/100.000. It is predominantly seen in the middle-aged and it appears to be more common in females. BCR is most prevalent in Caucasian populations. DIAGNOSTIC CRITERIA by The International Workshop -UCLA Required characteristics - Bilateral disease - ≥3 characteristic birdshot lesions peripapilary in 1 eye - Low-grade anterior chamber inflammation (≤1+cells) - Low-grade vitreous inflammation (≤2+) Supportive characteristics HLA-A29 + Retinal vasculitis and Cystoid Macular Oedema (CMO) Birdshot lesions were defined as being “cream-coloured, irregular or elongated, choroidal lesions with indistinct borders, the long axis of which is radial to the optic disk”

CASE REPORT A 52 years-old woman diagnosed of idiopathic bilateral posterior uveitis in 2005, with confirmed HLA-A29+ that suggested BSRC in 2009. AV:OD 0.5 EST 0.8;OS 0.2 , EST 0.5 From the beginning of the disease developed persistent refractory CME and diverse grade of vitritis despite being treated several times with intravitreal and systemic steroids, cyclosporine A, mycophenolate mofetil, tacrolimus, infliximab, adalimumab and intravitreal, and dexamethasone implants.

In Mars 2013 started treatment only with Tocilizumab with substantial improvement in the visual acuity (VA), CME, ocular inflammation (OS) and OCT images. That was maintained until the middle-end of 2015, then CME with very low-grade vitritis reappeared again only in the left eye (OS) despite of additional periocular steroids an intravitreal bevacizumab. In February 2016 she started additional off-label treatment with intravitreal Aflibercept in OS. Minos E et al. Birdshot chorioretinopathy: current knowledge and new concepts in pathophysiology, diagnosis, monitoring and treatment . Orphanet Journal of Rare Diseases .2016;11: 61

RESULTS After one month the patient presented complete resolution of the CME and a low-grade vitritis in OS and maintained no inflammation in the right eye (OD). Until now, she has required quarterly dose of Aflibercept OS and Tocilizumab as base therapy to maintain no CME and no inflammation in both eyes. AV 0,7 OA CONCLUSIONS Tocilizumab seems to be an effective therapy to BCR but with limited effect over time. The addition of aflibercept to tocilizumab can be useful to the management of CME in BCR. Mesquida M, Molins B, Llorenç V, Sainz de la Maza M and Adán A. Long-Term Effects of Tocilizumab Therapy for Refractory Uveitis-Related Macular Edema. Optalmol. 2014; 121 (12):2381-2386. Papo M. et al. Tocilizumab in severe and refractory non-infectiour uveítis.Clin Exp Rheumatol. 2014; 32 (Suppl 84): S75-S79. Mackensen F, Heinz C, Becker MD, Heiligenhaus A. Intravitreal bevacizumab (avastin) as a treatment for refractory macular edema in patients with uveitis: a pilot study. Retina. 2008;28(1):41–5. Weiss K, Steinbrugger I, Weger M, et al. Intravitreal VEGF levels in uveitis patients and treatment of uveitic macular oedema with intravitreal bevacizumab. Eye (Lond). 2009;23(9):1812–8.