scots , the stem cell ophthalmology treatment study , is the largest ophthalmology stem cell study registered at the national institutes of health ( www.clinicaltrials.gov identifier nct number 01920867 ) . all patients that meet eligibility criteria and were enrolled in the study received active treatment . bone marrow aspirated from the posterior iliac crest was separated to provide bone marrow - derived stem cells ( bmscs ) within a stem cell concentrate . inclusion criteria for scots include : -have objective , documented damage to the retina or optic nerve unlikely to improve or have objective , documented damage to the retina or optic nerve that is progressive . -have less than or equal to 20/40 best corrected central visual acuity in one or both eyes and/or an abnormal visual field in one or both eyes . -be at least 3 months post - surgical treatment intended to treat any ophthalmologic disease and be stable . -if under current medical therapy ( pharmacologic treatment ) for a retinal or optic nerve disease be considered stable on that treatment and unlikely to have visual function improvement ( for example , glaucoma with intraocular pressure stable on topical medications but visual field damage ) . -have the potential for improvement after bmscs treatment and be at minimal risk of any potential harm from the procedure . -be medically stable and able to be medically cleared by their primary care physician or a licensed primary care practitioner for the procedure . medical clearance means that in the estimation of the primary care practitioner , the patient can reasonably be expected to undergo the procedure without significant medical risk to health . exclusion criteria include : -patients who are not capable of an adequate ophthalmologic examination or evaluation to document the pathology . -patients who are not capable or not willing to undergo follow up eye exams with the principle investigator or their ophthalmologist or optometrist as outlined in the protocol . -patients who may be at significant risk to general health or to the eyes and visual function should they undergo the procedure . there were three arms of scots with the type of treatment chosen based on the degree of visual loss , etiology of visual loss , associated risk factors for the treatment arms and the patient 's medical risk status . an fda cleared class 2 medical device was used to separate the bone marrow aspirate into a stem cell concentrate . this concentrate ( approximately 1415 cm ) contained 1.2 billion total nucleated cells including mesenchymal stem cells . 3 cm of concentrate was used for retrobulbar injection , 0.05 cm for intravitreal injection , 0.1 cm for subretinal injection , 0.2 cm for intraoptic nerve injection , and the remainder of the concentrate for intravenous injection . arm 1 consists of retrobulbar and subtenon injection , followed by intravenous injection , of stem cell concentrate . patients with ophthalmic conditions which preclude safe or effective utilization of intravitreal injection of concentrate , such as the presence of silicon oil , may be offered arm 1 if meeting inclusion criteria . arm 2 consists of retrobulbar , subtenon and intravitreal administration , followed by intravenous infusion , of concentrate . patients meeting inclusion criteria with visual acuity between 20/40 and 20/200 in one or both eyes and/or visual loss may be offered arm 2 . arm 3 is reserved for retinal and optic nerve patients with severe visual loss meaning visual acuity of 20/200 or worse in at least one eye . typically patients admitted to arm 3 have much poorer vision . arm 3 consists of the better - seeing eye receiving the same treatment as arm 1 or more typically , arm 2 , and the eye with more extensive visual acuity loss receiving a core pars plana vitrectomy with subretinal or intra - optic nerve injection of concentrate followed by intravenous infusion of stem cells . follow up was required at 1 , 3 , 6 and 12 months after treatment with reporting of the eye exam results to the principal investigator and study director . the importance of scots rests with its openness to various retinal and optic nerve diseases . scots is focused on the cellular damage to tissue which is causing the visual loss . this allows the study to enroll and assess improvements in a number of diseases including visual loss that may be a result of more than one disease . scots also provides bmscs in close proximity to the damaged tissue which may maximize paracrine effects . treatment is provided in a fully licensed ambulatory surgical center in coconut creek , florida , usa . the patient is a 54 year old female who developed sudden vision loss in the right eye to 20/400 on june 6 , 2010 . she was diagnosed with non - arteritic anterior ischemic optic neuropathy ( naion ) by her optometrist and ophthalmologist as her attack was sudden , painless , and she had a swollen optic nerve in the right eye . she felt she had lost the whole superior visual field in that attack as well as the central vision in the right eye . at that time , visual acuity in the left eye was 20/30 and the left eye had small inferior and superior arcuate visual field defects . four months later , she experienced a second episode of vision loss in the right eye and her inferior nasal visual field was obviously lost . a third episode of vision loss in the right eye occurred in january 2011 , 7 months after the first attack . a second opinion was sought and concurred that it was probably naion , although a rare variant with recurrences . her fourth visual attack was on her  good  left eye in june 2011 , a year after the first attack on her right eye . her visual acuity of the left eye fell to 20/70 with superior and inferior arcuate defects . her first exam by a neuro - ophthalmology unit on june 7 , 2011 showed visual acuities of 20/400 eccentrically in the right eye and 20/70 in the left eye . visual field analysis of the right and left eyes performed using a humphrey visual field analyzer with program 30 - 2 revealed both superior temporal and inferonasal losses . ocular coherence tomography of macular thickness showed thinning of the retinal nerve fiber layers in the lowest percentile compared to her age - matched controls . mri of the brain did not demonstrate white matter lesions suggesting demyelinating disease and there was no orbital abnormality . hematologic evaluation showed a low thyroid stimulating hormone , slightly elevated t3 and t4 , normal complete blood count , normal chemistries , and a normal erythrocyte sedimentation rate . further testing for autoimmune disorders included a neuromyelitis optica antibody measuring 1.398 ( below the 3.0 cut - off for  positive  ) , a positive thyroid stimulating immunoglobulin ( 313 , n < 130 ) for graves disease , a positive microsomal antibody at 380 ( n < 35 ) for auto - immune thyroid disorders , a slightly elevated thyroglobulin antibody at 50 ( n < 29 ) , a positive anti - saccharomyces cerevisiae ab 32 ( asca iga , n < 20 ) for gluten - sensitive enteropathy . important negatives were antinuclear antibodies , rapid plasma reagin , angiotensin converting enzyme , lysozyme , toxoplasmosis , lyme 's ab , herpes simplex virus 1 and 2 ab , b12 and anti - phospholipid antibodies . blood sent to an oregon laboratory revealed anti - optic nerve antibodies to both 35 and 70 kda proteins . multiple bands are common in auto - immune disorders , but are non - specific . the patient received a steroid pulse therapy after the second episode of vision loss in the right eye and the visual acuity in the left eye improved from 20/70 to 20/20 . daily mycophenylate ( 1,500 mg ) began but did not prevent two more attacks of vision loss in the left eye to 20/70 ( nmo ab 1.496 on august 8 , 2011 ) and 20/80 ( nmo ab 1.9 on 3/12 ) . her neuromyelitis optica antibody titers never exceeded 3.0 and were not rechecked until august 14 , 2011 . after the third steroid pulse therapy , her visual acuities were between 20/35020/400 in the right eye and 20/70 in the left eye , and her general health remained stable from march , 2012 , until her scots treatment in november , 2013 . postoperative visual field analysis was performed using the humphrey field analyzer 30 program ( carl zeiss meditech inc . , oberkochen , germany ) at the scots center in florida , usa on november 4 , 2013 . results showed a mean deviation ( md ) of 26.25 in the right eye and 6.25 in the left eye . humphrey 30 visual field data of the right ( figure 1 ) and left eyes ( figure 2 ) . the patient was assigned to scots arm 3 with a vitrectomy and intra - optic nerve injection of bmscs in the right eye . her left eye received arm 2 with retrobulbar , subtenon and intravitreal injection of bmscs . the surgery was performed under general anesthesia without complications and with no cessation of her mycophenylate on november 5 , 2013 . on december 9 , 2013 ( 1 month after scots treatment ) , she reported  brighter and clearer vision  and was able to safely drive the hour and a half to her check - up . her visual acuities on that day had improved to 20/300 in the right eye and 20/15 in the left eye . at 3 months after scots treatment , the macular thickness had improved to 6.388 in the right eye and 6.578 in the left eye . on february 5 , 2014 , 3 months after scots treatment , her fast retinal nerve fiber layer thickness had improved to 39.02 on average in the right eye and 83.02 in the left eye ( figure 3 ) . fast retinal nerve fiber layer optic nerve thickness maps taken on february 5 , 2014 . 6 months after scots treatment , her best corrected visual acuity remained 20/150 in the right eye and 20/15 in the left eye . in august , 2014 , 9 months after scots treatment , the patient reported that she subjectively felt healthier than she had felt since 2010 . she had tapered her mycophenylate to 500 mg per day , required no steroids since surgery , and was on stable amounts of methimazole ( 5 mg ) , evista , dehydroepiandrosterone ( dhea ) , and vitamin e. her blood tests demonstrated a thyroid stimulating immunoglobulin down to 88 from the 313 in november 6 , 2013 , microsomal ab down to 149 from 380 , and asca iga 0 and nmo antibody 0.0 . she still had a measurable anti - optic nerve antibody to the 35 kda protein , and no ab to the 70 kda protein . on november 12 , 2014 , i.e. , 12 months after scots treatment , the patient had a snellen acuity of 20/300 in the right eye through a now - denser posterior subcapsular cataract and 20/15 in the left eye through a trivial cataract . her early treatment of diabetic retinopathy study ( etdrs ) distance score was 15 in the right eye and 50 in the left eye . biomicroscopy showed a posterior subcapsular cataract in the right eye and a lesser one in the left eye with an intraocular pressure of 9 in the right eye and 11 in the left eye . at 12 months after scots treatment , the visual fields for the right eye averaged 20.52 db with a temporal island of intact vision sliding toward fixation ( figure 5 ) and that for the left eye averaged 0.56 db with a residual inferonasal spotty defect ( figure 6 ) . the visual field improved at 12 months in both eyes despite the right macula measured thinner than it had at the 3 and 6 month visits ( figure 7 ) . humphrey visual field of the right eye on november 12 , 2014 ( 1 year after the stem cell ophthalmology treatment study treatment ) . humphrey visual field of the left eye on november 12 , 2014 ( 1 year after the stem cell ophthalmology treatment study treatment ) . macular thickness maps taken on november 12 , 2014 ( 1 year after the stem cell ophthalmology treatment study treatment ) . after scots treatment , her optical coherence tomography macular retinal thickness data showed that manular thickness was 5.973 in the right eye ( in the lowest 5 percentile compared to her age - matched controls ) ( figure 7 ) and 6.905 in the left eye ( in the normal 595 percentile for her age ) . at 1 year after scots treatment , her circular peripapillary fast retinal nerve fiber layer thickness was 40.56 in the right eye ( 1 percentile ) , with the nasal quarter of the nerve now averaging in the normal thickness for her age , and 67.64 in the left eye ( still the lowest first percentile ) , with the temporal half of the nerve back in the normal retinal nerve fiber layer thickness ( figure 8) . fast retinal nerve fiber layer thickness analysis report taken on november 12 , 2014 ( 1 year after the stem cell ophthalmology treatment study treatment ) . in this case report , a relapsing auto - immune optic neuropathy caused progressive bilateral visual loss , which started in june 2010 and lasted till fall 2013 with visual acuities of 20/35020/400 in the right eye and 20/70 in the left eye . the patient chose to participate in the scots study and underwent a right eye vitrectomy with intra - optic nerve injection of bmscs in the right eye and retrobulbar , subtenon and intravitreal injection of bmscs in the left eye . after scots treatment , her central acuity was 20/150 for the right eye at 3 months after scots treatment , remained this level for a 6-month period , and then declined to 20/300 at 12 months after scots treatment at which time a psc cataract had formed in the vitrectomized eye . an intraocular lens was inserted at 13 months after scots treatment and vision returned to 20/150 at 15 months after scots treatment . the visual acuity of the left eye was 20/15 within the first 3 weeks after scots treatment and remained stable throughout the 1st year . at 15 months after scots treatment , her visual acuity was 20/20 in the left eye . both eyes continued to have visual field improvements at 1 year after scots treatment . at 3 and 6 months after scots treatment , both macular thickness maps and fast retinal nerve fiber layer thickness improved . despite the thinner measurements of the macular thickness and fast retinal nerve fiber layer thickness in the right eye at 9 and 12 months after scots treatment , the visual field function continued to improve in both eyes . based on the scans , the decreases in macular thickness and fast retinal nerve fiber layer thickness in the right eye mainly occurred in the nasal and inferior regions , corresponding to the superior temporal field . summary of best corrected visual acuities at 1 year after scots treatment , the impaired visual field of the right eye remained primarily in the temporal part . kok et al . ( 2013 ) reported a linear relationship between the optical coherence tomography - effective optical density of cataracts and an underestimation of retinal nerve fiber layer thickness . given the development of a moderately dense cataract in the right eye in conjunction with an improved visual field , it is plausible that a degree of the measured decrease in retinal nerve fiber layer thickness is an artifact , according to mwanza et al . immune modulation as described by karantalis and hare ( 2015 ) may play a role in this later response . in a review article by pula and macdonald ( 2012 ) , optic neuritis can be classified as typical ( as in multiple sclerosis ) or atypical ( not associated with multiple sclerosis and which may improve after steroid treatment ) . in atypical optic neuritis , autoimmune optic neuritis is associated with connective tissue diseases such as systemic lupus erythematosus , vasculitis , sarcoidosis , and neuromyelitis optica . treatment for typical or demyelinating optic neuritis may include intravenous steroids . as shown in the optic nerve treatment trial , steroids may hasten the visual recovery but do not change the overall outcomes of visual acuity after 6 months of treatment . therapeutic plasma exchange may be used to potentially help remove pathogenic immunoglobulins or complement from plasma ; immunoadsorption is sometimes used similar to therapeutic plasma exchange but with absorption of immunoglobulins . other interventions explored have included the use of statins , heat killed mycobacterium w , and fingolimod ( used for the prevention of multiple sclerosis relapses ) . there are few studies regarding recurrent autoimmune optic neuropathy to which we might compare scots . in a study by stiebel - kalish et al . ( 2010 ) , patients with recurrent inflammatory optic neuropathy treated with intravenous immunoglobulins acquired stable vision and in most cases , steroid avoidance was achieved but there was no visual improvement . treatments for atypical optic neuritis also primarily involve steroids and mainly focus on associated systemic diseases , if identified . systemic causes can include vasculitis such as microscopic polyarteritis , wegener 's granulomatosis , henoch - schnlein purpura ; collagen vascular diseases include systemic lupus erythematosus , neurosarcoidosis , and sjgren 's syndrome . neuromyelitis optica or devic 's disease is an inflammatory disease of the central nervous system producing optic neuritis and myelitis . according to collongues et al . ( 2010 ) , there is a female predominance ; the median age of onset is the mid to late 30s with more than 80% of patients having a relapsing course with progressive disability ( collongues et al . , 2010 ) . neuromyelitis optica tends to be worse than multiple sclerosis for both visual loss and physical disability . this identifies an antibody to the plasma membrane channel aquaporin-4 which is responsible for water movement . aquaporin-4 is present in the astrocytes which form the blood - brain barrier and neuromyelitis optica - igg is associated with 7791% of sensitivity and 94100% of specificity for neuromyelitis optica , as concluded by wingerchuk et al . ( 2004 ) , neuromyelitis optica may be present without transverse myelitis . in this patient , neuromyelitis optica antibodies were only weakly present , and given the other antibodies identified , a diagnosis of relapsing autoimmune optic neuritis was made . this 54 year old female patient had significant improvements in visual acuity , visual field and ocular coherence tomography following treatment with autologous bmscs as given in the protocols developed for the scots . while this is a single patient and results may not be reproducible , autologous bmscs may prove a valuable addition to treatment of relapsing autoimmune optic neuritis as well as other optic neuropathies , demonstrating an immunologic component .
we present the results from a patient with relapsing optic neuropathy treated within the stem cell ophthalmology treatment study ( scots ) . 
 scots is an institutional review board approved clinical trial and has become the largest ophthalmology stem cell study registered at the national institutes of health to date ( www.clinicaltrials.gov identifier nct 01920867 ) . 
 scots utilizes autologous bone marrow - derived stem cells ( bmscs ) for treatment of retinal and optic nerve diseases . 
 pre - treatment and post - treatment comprehensive eye exams of a 54 year old female patient were performed both at the florida study center , usa and at the eye center of columbus , usa . as a consequence of a relapsing optic neuritis , the patient 's previously normal visual acuity decreased to between 20/350 and 20/400 in the right eye and to 20/70 in the left eye . 
 significant visual field loss developed bilaterally . 
 the patient underwent a right eye vitrectomy with injection of bmscs into the optic nerve of the right eyeand retrobulbar , subtenon and intravitreal injection of bmscs in the left eye . at 15 months after scots treatment , 
 the patient 's visual acuity had improved to 20/150 in the right eye and 20/20 in the left eye . 
 bilateral visual fields improved markedly . both macular thickness and fast retinal nerve fiber layer thickness 
 were maximally improved at 3 and 6 months after scots treatment . 
 the patient also reduced her mycophenylate dose from 1,500 mg per day to 500 mg per day and required no steroid pulse therapy during the 15-month follow up .