nonarteritic anterior ischemic optic neuropathy ( naion ) is a relatively frequent cause of irreversible vision loss in the middle - aged and elderly , with an estimated annual incidence of 2.3 per 100,000 . the risk factors for naion can be divided into two groups : systemic and ocular . the systemic factors include nocturnal hypotension , sleep apnea syndrome , arterial hypertension , diabetes mellitus , coronary artery disease , arteriosclerosis , hypercholesterolemia and prolonged surgical procedures such as spinal or cardiac bypass surgery [ 2 , 3 , 4 ] . a significant association of naion with a number of ocular and optic nerve head conditions has also been reported . these include small and crowded optic disks , angle closure glaucoma or other causes of markedly raised intraocular pressure , optic disk drusen and cataract extraction [ 4 , 5 ] . in addition , reports of thrombotic tendencies in some patients with naion have raised the question of whether there is a causative link between thrombophilia and naion [ 2 , 6 , 7 ] . here we present , to the best of our knowledge , the first case of naion associated with combined protein s deficiency and heterozygosity for prothrombin g20210a mutation . a 58-year - old male patient presented with painless visual loss in his right eye upon awakening in the morning . his best - corrected visual acuity was 3/10 in the right eye and 10/10 in the left eye . funduscopic examination of the right eye revealed a hyperemic optic disk with blurred superior optic disk border , sectoral nerve fiber layer edema , few flame - shaped peripapillary hemorrhages and solitary cotton - wool exudates . examination of the fellow eye showed a small left optic disk with a cup - disk ratio of 0.2 and slight blurring of the nasal margin , indicating a probable contributory mechanical effect in the pathogenesis of the disease . complete blood count , erythrocyte sedimentation rate and c - reactive protein were normal ; therefore , the diagnoses of giant cell arteritis or other arteritic optic neuropathies were considered unlikely . the clinical and laboratory findings were compatible with naion and a complete workup of potential cardiovascular risk factors was ordered . it revealed hyperlipidemia , arterial hypertension and high - risk coronary artery disease . due to the family history of two episodes of deep vein thrombosis in the patient 's daughter ( before and during pregnancy ) , laboratory testing included protein c , protein s , antithrombin iii , lupus anticoagulant , homocysteine level , anticardiolipin antibodies , activated protein c resistance and prothrombin g20210a mutation . the results revealed a double thrombophilic defect , namely congenital protein s deficiency and heterozygosity for prothrombin g20210a mutation , which were also identified in the patient 's daughter . anticoagulant therapy with warfarin was initiated and the patient also underwent a triple bypass surgery . follow - up visits were performed at 1 week , 2 weeks and at 1 , 3 , and 6 months . the right optic disk edema had resolved , leaving a pale superior optic nerve head ( atrophy ) . visual acuity in the right eye had slightly improved to 4/10 ; however , the dense inferior altitudinal field defect had remained unchanged . re - evaluation at six months revealed no significant changes in visual acuity , funduscopic findings and visual field . the patient is currently treated with warfarin ( target inr 2.53.0 ) , atorvastatin ( 20 mg / day ) , irbesartan ( 150 mg / day ) and metoprolol ( 25 mg twice a day ) . several observations have suggested that thrombophilic disorders , such as elevated homocysteine , lipoprotein(a ) and high frequency of leiden mutation , may be pathogenetically relevant in the development of naion by increasing the risk for venous thromboembolism ( vte ) [ 2 , 6 , 7 ] . on the other hand , recent studies did not demonstrate an association between naion and a wide range of thrombophilic risk factors . however , naion is primarily not a thromboembolic disorder but an arterial ischemic disorder of the optic nerve head [ 3 , 8 ] . its pathogenesis has been attributed to optic nerve head hypoperfusion , which is mostly due to nocturnal hypotension [ 5 , 8 ] . an acute blood flow reduction in the prelaminar portion of the optic disk is generally accepted as the underlying mechanism for the development of naion . six - month follow - up of the present patient revealed a slight improvement in visual acuity ( from 3/10 to 4/10 ) , which is in consistence with previous reports . in the review by hayreh and zimmerman   looking at the natural history of visual outcome in naion , 41% of patients seen within two weeks of symptom onset and with initial visual acuity of 20/70 or worse showed improvement at 6 months . according to the same study , therefore , although the patient is still under observation , a further change in his visual acuity or visual field is not expected unless a recurrence of naion occurs . however , reported episodes of recurrence in the same eye are uncommon and range from 3% to 6.4% [ 10 , 11 ] . the only significant association for recurrence of naion was with nocturnal arterial hypotension , while thrombophilia was not associated with recurrence of naion [ 3 , 10 ] . although it is uncommon for naion to recur in the same eye , it may involve the fellow eye in 14.7% of patients after a median follow - up of 5 years . a history of diabetes has been associated with increased risk of naion in the fellow eye . in a study by salomon et al . , none of the parameters tested ( i.e. , gender , age at onset of first naion , ischemic heart disease , hypercholesterolemia , diabetes , arrhythmia , hypertension , history of stroke , current smoking , crowded disk , and prothrombotic factors ) proved to be significant predictors of second eye involvement . according to these findings , the risk of second eye involvement is not increased in the present patient . however , a regular follow - up is suggested , because naion is a multifactorial disease and other risk factors so far unknown may also play a role . in conclusion , although we report the first case of naion associated with a double thrombophilic defect ( protein s deficiency and prothrombin g20210a mutation ) , the inference that naion was invoked by the thrombophilia is difficult to reconcile with the cardiovascular risk profile and the crowded disks also coexistent in our patient . hence we suggest that the first line of investigation in all patients with naion involves assessment of cardiovascular risk factors , in order to detect and treat even life - threatening conditions , such as coronary artery disease , whenever possible . however , it can not be excluded that thrombogenic tendency may act as a trigger in susceptible individuals . therefore careful history taking is important , in order to identify naion patients with thrombophilic defects . thrombophilia screening is justifiable in selected naion cases : young ( less than 45 years of age ) patients without vasculopathic risk factors , bilateral simultaneous naion or recurrent naion in the same eye , idiopathic or recurrent vte , positive family history of vte , and vte in young age or in unusual sites ( e.g. cerebral , hepatic , mesenteric , or renal vein ) [ 15 , 16 ] .
we report the first case of nonarteritic anterior ischemic neuropathy ( naion ) associated with double thrombophilia : protein s deficiency and prothrombin g20210a mutation . 
 a 58-year - old man is presented including the clinical and laboratory findings , cardiovascular profile and thrombophilia screening . 
 the patient presented with 3/10 vision and an inferior altitudinal defect in the right eye . 
 funduscopic examination of the right eye revealed a hyperemic optic disk with blurred superior optic disk border and sectoral nerve fiber layer edema . 
 complete blood count , erythrocyte sedimentation rate and c - reactive protein were normal , suggesting a naion . 
 a workup of cardiovascular risk factors revealed hyperlipidemia , arterial hypertension and high - risk asymptomatic coronary artery disease . due to the family history of deep vein thrombosis in the patient 's daughter , 
 a thrombophilia screening was additionally performed . 
 the results revealed a double thrombophilic defect , namely congenital protein s deficiency and heterozygosity for prothrombin g20210a mutation , which were also identified in the patient 's daughter . 
 anticoagulant warfarin therapy was initiated and the patient underwent a triple bypass surgery . at three - month follow - up , 
 the right optic disk edema had resolved , leaving a pale superior optic nerve head . 
 visual acuity in the right eye had slightly improved to 4/10 ; however , the dense inferior altitudinal field defect had remained unchanged . 
 the patient is currently treated with warfarin , atorvastatin , irbesartan and metoprolol . 
 this case suggests that the first line of investigation in all patients with naion involves assessment of cardiovascular risk factors . 
 however , careful history taking will identify naion patients who are eligible for additional thrombophilia screening : young patients without vasculopathic risk factors , bilateral or recurrent naion , idiopathic or recurrent venous thromboembolism ( vte ) , positive family history of vte , and vte in young age or in unusual sites ( e.g. cerebral , hepatic , mesenteric , or renal vein ) .