macular edema is one of the most common complications in eyes with branch retinal vein occlusion ( brvo ) and a major cause of visual deterioration.1 in addition to macular grid laser photocoagulation,2 intravitreal injections of steroids,3 vitrectomy,4 and intravitreal injection of off - label bevacizumab,5 a monoclonal antibody against human vascular endothelial growth factor ( vegf ) , have been used to treat macular edema . tumor necrosis factor ( tnf)- is known to play a major role in inflammation , and is used to treat rheumatoid arthritis ( ra ) . infliximab , a humanized monoclonal anti - tnf- antibody , and etanercept , a dimeric fusion protein consisting of the extra - cellular domain of tnf receptor ii and the fc region of human immunoglobulin , are approved and used clinically to treat patients with ra.6,7 tnf- is known to break down the blood  retinal barrier,8 and neutrophils activated by tnf- release elastase which causes damage to endothelial cells and an increase in microvascular permeability . there are reports that anti - tnf- is effective in treating macular edema associated with uveitis9 and diabetic retinopathy.10 we report a case of macular edema secondary to brvo in which the degree of macular edema decreased during anti - tnf- treatment for ra , increased when the anti - tnf- treatment was stopped , then decreased again when the anti - tnf- treatment was restarted . a 59-year - old woman noticed a decrease in the vision of her right eye in early june 2006 , and because she was being treated for ra in the department of orthopedics at nagoya university hospital , she was referred to the department of ophthalmology at the same institution on 30 june 2006 . at that time , she was being treated with prednisolone 5 mg / day , diclofenac sodium 75 mg / day , salazosulfapyridine 1000 mg / day , and methotrexate 8 mg / week for her ra . her best - corrected visual acuity ( bcva ) was 20/40 od , and macular edema due to a brvo was detected . her foveal thickness determined by optical coherent tomography ( oct ; oct2000 or stratus , carl zeiss meditec , oberkochen , germany ) was 679 m . after obtaining approval from the nagoya university hospital internal ethics review board and her informed consent , she was treated with intravitreal bevacizumab ( ivb ) beginning on 07 august 2006 . she was injected with ivb three times , and the foveal thickness after each injection was 298 , 317 , and 237 m , and the bcva was 20/40 , 20/40 , and 20/33 , respectively . thus , the final bevacizumab injection was on november 14 , 2006 , and she was followed up without any ophthalmologic treatment . on 28 december 2006 , the foveal thickness determined by oct was 629 m , and the bcva was 20/50 ( figures 1a and 1b ) . because the ra was not well controlled with the oral treatment listed above , intravenous injections of infliximab 150 mg were started by the orthopedists on march 29 , 2007 . after the sixth injection of infliximab 150 mg , the amount of infliximab was increased to 200 mg , and after the second injection of 200 mg infliximab on february 7 , 2008 , the foveal thickness in her right eye decreased to 314 m , and her visual acuity was 20/25 ( figure 1c ) . there was no recurrence of macular edema during the infliximab injections , and her right foveal thickness was 309 m and her bcva was 20/20 on september 26 , 2008 ( figures 1d and 1e ) . the infliximab injections were stopped on december 12 , 2008 because she developed pneumonia and had joint surgery . she did not return to our department until may 29 , 2009 , more than five months after her last infliximab injection . we found that the macular edema had recurred , and the foveal thickness was 494 m ( figures 2a and 2b ) . on june 5 , 2009 , her orthopedists started a 25 mg / week subcutaneous injection of etanercept to treat the ra . on july 3 , 2009 , about one month after the start of the etanercept injections , the foveal thickness had decreased to 369 m ( figure 2c ) and , on october 23 , 2009 , about five months after the start of the etanercept injections , the foveal thickness was 260 m ( figures 2d and 2e ) . her bcva in the right eye was 20/25 or better throughout the period of etanercept treatment . we report the findings in a patient whose macular edema regressed after infliximab injections , as a secondary effect to her treatment for ra , then recurred after stopping the injections . the infliximab injections were started nine months after the onset of the brvo , and etanercept injection was started three years after the onset . these findings strongly suggest that these anti - tnf- drugs were effective in reducing the degree of macular edema . however , the foveal thickness decreased gradually for more than six months after starting the infliximab , and more than three months after starting etanercept . in addition , when the infliximab was stopped for eight months , the macular edema recurred . these results suggest that repeated anti - tnf- injections are needed to obtain the maximum effect , and the injections need to be continued to remain effective . because the reduction of foveal thickness was transient , similar to anti - vegf treatment , it is suggested that there could have been a systemic process occurring that may have influenced this localized inflammatory process . both vegf and tnf- are known to break down the blood  retinal barrier,8 and there are some reports that anti - tnf- treatment is effective against macular edema associated with uveitis.9 additionally , sfikakis et al reported that anti - tnf- treatment was effective in four of six eyes with diabetic macular edema , but not for two eyes with an epiretinal membrane.10 there is still no evidence that the ocular level of tnf- is increased in eyes with macular edema secondary to brvo.11 however , because injections of steroids are effective in treating the macular edema secondary to brvo,3 low - grade inflammation seems to play a role in the pathogenesis of chronic macular edema secondary to brvo . macrophages are found on the inner limiting membrane of eyes with macular edema,12 and tnf- is known to activate macrophages and increase vegf expression.13 in addition , there has been a report of a significant reduction of macrophages and vegf in ra patients after anti - tnf- treatment.14 these reports suggest that anti - tnf- therapy resolve the macular edema not by decreasing vascular permeability directly , but by decreasing the expression of vegf and/or other proteins related to inflammation . from the clinical course of our patient , we conclude that tnf- plays a role in the pathogenesis of her chronic macular edema secondary to brvo . these findings suggest that anti - tnf- should be considered for the treatment of macular edema secondary to brvo .
a patient with macular edema secondary to a branch retinal vein occlusion ( brvo ) was treated with intravenous injections of infliximab , an antitumor necrosis factor ( tnf)- antibody , for her rheumatoid arthritis ( ra ) . before the injection , 
 the thickness of the right fovea , determined by optical coherent tomography , was 629 m and the best - corrected visual acuity ( bcva ) was 20/50 . 
 after eight injections of infliximab and 10 months after the first injection , her foveal thickness was decreased to 293 m and the visual acuity improved to 20/20 . 
 there was no recurrence of macular edema during the infliximab injections . 
 however , the infliximab injection was stopped because the patient developed pneumonia . 
 eight months after stopping the infliximab injection , her foveal thickness increased to 494 m . to treat the ra , 
 her orthopedists began weekly subcutaneous injections of etanercept , a fusion protein of a section of the tnf receptor and immunoglobulin . 
 five months later , the foveal thickness had decreased to 260 m , and the visual acuity remained at 20/25 + . because tnf- is known to break down the blood 
 retinal barrier , the improvements in our case suggest that tnf- plays a role in the pathogenesis of macular edema in some patients with brvo .