twenty - three consecutive , previously untreated patients with acute unilateral on were recruited from the ophthalmology outpatient clinics of isfahan university of medical sciences , iran between october 2009 and february 2010 . these included four men and 19 women , with a mean ( standard deviation [ sd ] ) age of 27.2 ( 7.0 ) years , ranging from 19 to 47 years .
the inclusion criterion was typical clinical presentation of acute unilateral on before the age of 50 years and exclusion criteria were bilateral on , recurrent on and any disease or anomaly of the contralateral eye .
no patient had a history of any major systemic diseases , including cardiovascular disease , arterial hypertension , hyperlipidemia or diabetes mellitus .
all patients underwent neurologic and ophthalmologic examinations including visual acuity assessment , direct ophthalmoscopy and measurement of visual evoked potentials ( vep ) .
the tenets of the declaration of helsinki were followed , institutional ethical committee approval was granted , patients were informed about the doppler method ; and an informed consent form was signed by each participant . on was diagnosed by an expert ophthalmologist ( ad ) .
cases of acute unilateral on were identified according to the degree of decrease in visual acuity , impaired perimetry findings , slight swelling of the optic disc and facultative retro- or parabulbar pain , afferent papillary defect and delayed vep responses .
the contralateral eye in all patients was un - affected by clinical signs of on before the study began .
however , we could not exclude the possibility that subclinical damage to the contralateral optic nerve may have occurred , although the veps in these eyes were normal .
multiple sclerosis ( ms ) was presumed to be the cause of on in 18 patients , with no obvious cause in the remaining five .
the best corrected visual acuity of the affected eyes varied from counting fingers to 20 / 20 ; the best corrected visual acuity of unaffected eyes was at least 20 / 20 in all cases .
the systolic and diastolic blood pressures measured during blood flow velocity investigations did not exceed 130 and 85 mmhg , respectively .
orbital doppler and gray - scale sonography was performed within one to seven days of presentation , prior to the initiation of corticosteroids treatment .
cdi of the eye was performed in all individuals by two expert sonographers ( mk and mr ) using a colour doppler unit and a 7.5- to 10-mhz linear - array transducer ( model g-60 ; siemens , erlangen , germany ) .
the nerve diameter was measured on both sides , with the unaffected nerve serving as a control .
a difference in nerve diameter of 0.3 mm or more , compared with the contralateral side , was defined as a sign of nerve thickening .
the patients were examined in the supine position in order to avoid any pressure on the eye .
sterile coupling gel was applied to their closed eyelids , with the examiner 's hand resting on the orbital margin to minimize pressure on the globe , and real - time gray - scale and colour - flow images were obtained .
we obtained peak systolic velocity ( psv ) and end - diastolic velocity ( edv ) measurements in the oa , cra and pcas of both orbits and used these to calculate the vascular resistance ( expressed by the ri and pi ) using the formulas ri = ( psv - edv ) / psv   and pi = ( psv - edv / vmean , where vmean = 1/3 ( psv - edv ) + edv , in all patients .
signals from short pca can be located in the lateral and medial sections of the eyeball and since numerous branches of short pcas were available for assessment , only the medial branch was chosen for analysis in this study . on the basis of an estimated standard deviation of 1.5 and accounting for pair - wise comparisons , we determined that 23 patients would be required to yield 80% power to detect ( with a two - sided alpha of 0.05 ) a 1.0 mm mean difference in optic nerve diameter .
psv , edv , ri , and pi obtained from the oa , cra , pcas , and the optic nerve diameter in the orbit with on were compared with those from the contralateral orbit without on using a paired student 's t - test .
the utility of optic nerve diameter , psv , edv , ri , and pi in diagnosing on was examined by analysis of the area under receiver operating characteristic ( roc ) curves , with sensitivity was plotted as a function of 1- specificity .
areas under the roc curves were compared using the algorithm developed by delong et al . .
all tests for statistical significance were two - tailed and performed assuming a type i error probability < 0.05 .
twenty - three consecutive , previously untreated patients with acute unilateral on were recruited from the ophthalmology outpatient clinics of isfahan university of medical sciences , iran between october 2009 and february 2010 . these included four men and 19 women , with a mean ( standard deviation [ sd ] ) age of 27.2 ( 7.0 ) years , ranging from 19 to 47 years .
the inclusion criterion was typical clinical presentation of acute unilateral on before the age of 50 years and exclusion criteria were bilateral on , recurrent on and any disease or anomaly of the contralateral eye .
no patient had a history of any major systemic diseases , including cardiovascular disease , arterial hypertension , hyperlipidemia or diabetes mellitus .
all patients underwent neurologic and ophthalmologic examinations including visual acuity assessment , direct ophthalmoscopy and measurement of visual evoked potentials ( vep ) .
the tenets of the declaration of helsinki were followed , institutional ethical committee approval was granted , patients were informed about the doppler method ; and an informed consent form was signed by each participant .
cases of acute unilateral on were identified according to the degree of decrease in visual acuity , impaired perimetry findings , slight swelling of the optic disc and facultative retro- or parabulbar pain , afferent papillary defect and delayed vep responses .
the contralateral eye in all patients was un - affected by clinical signs of on before the study began .
however , we could not exclude the possibility that subclinical damage to the contralateral optic nerve may have occurred , although the veps in these eyes were normal .
multiple sclerosis ( ms ) was presumed to be the cause of on in 18 patients , with no obvious cause in the remaining five .
the best corrected visual acuity of the affected eyes varied from counting fingers to 20 / 20 ; the best corrected visual acuity of unaffected eyes was at least 20 / 20 in all cases .
the systolic and diastolic blood pressures measured during blood flow velocity investigations did not exceed 130 and 85 mmhg , respectively .
orbital doppler and gray - scale sonography was performed within one to seven days of presentation , prior to the initiation of corticosteroids treatment .
cdi of the eye was performed in all individuals by two expert sonographers ( mk and mr ) using a colour doppler unit and a 7.5- to 10-mhz linear - array transducer ( model g-60 ; siemens , erlangen , germany ) .
the nerve diameter was measured on both sides , with the unaffected nerve serving as a control . a difference in nerve diameter of 0.3 mm or more , compared with the contralateral side , was defined as a sign of nerve thickening .
the patients were examined in the supine position in order to avoid any pressure on the eye .
sterile coupling gel was applied to their closed eyelids , with the examiner 's hand resting on the orbital margin to minimize pressure on the globe , and real - time gray - scale and colour - flow images were obtained .
we obtained peak systolic velocity ( psv ) and end - diastolic velocity ( edv ) measurements in the oa , cra and pcas of both orbits and used these to calculate the vascular resistance ( expressed by the ri and pi ) using the formulas ri = ( psv - edv ) / psv   and pi = ( psv - edv / vmean , where vmean = 1/3 ( psv - edv ) + edv , in all patients .
signals from short pca can be located in the lateral and medial sections of the eyeball and since numerous branches of short pcas were available for assessment , only the medial branch was chosen for analysis in this study .
on the basis of an estimated standard deviation of 1.5 and accounting for pair - wise comparisons , we determined that 23 patients would be required to yield 80% power to detect ( with a two - sided alpha of 0.05 ) a 1.0 mm mean difference in optic nerve diameter .
psv , edv , ri , and pi obtained from the oa , cra , pcas , and the optic nerve diameter in the orbit with on were compared with those from the contralateral orbit without on using a paired student 's t - test .
the utility of optic nerve diameter , psv , edv , ri , and pi in diagnosing on was examined by analysis of the area under receiver operating characteristic ( roc ) curves , with sensitivity was plotted as a function of 1- specificity .
areas under the roc curves were compared using the algorithm developed by delong et al . .
all tests for statistical significance were two - tailed and performed assuming a type i error probability < 0.05 .
on involved the right eye in 12 patients ( 52.2% ) and the left eye in the remaining 11 ( 47.8% ) patients . of the 23 eyes with on , 20 ( 86.9% ) showed a thickening of the affected optic nerve . only three eyes with on had a difference in nerve diameter less than 0.3 mm .
the increase in diameter of the affected nerve compared with the unaffected contralateral nerve averaged ( sd ) 1.1 ( 0.6 ) mm ( range , 0.1 to 2.2 mm ) . when the cut - off value for nerve pathology was set at a nerve diameter of 4 mm , 15 ( 65.2% ) of the affected nerves and 100% of the unaffected nerves were correctly assessed .
the mean ( sd ) values of parameters obtained from cdi measurements in the oa , cra , pcas and optic nerve in the 23 pairs of eyes with and without on are shown in table 1 . as expected ,
the mean ( sd ) optic nerve diameter was 4.1 ( 0.8 ) mm for eyes with on and 3.0 ( 0.4 ) mm for eyes without on ( p < 0.001 ) .
there were no statistically significant differences between eyes with and without on in terms of psv , edv , ri , and pi in oa and cra measurements .
the mean ri in the pcas was slightly lower in eyes with on than in control eyes ( 0.60 vs. 0.64 , p < 0.05 ) .
the areas under the roc curves for the occurrence of on for orbital blood flow velocities and resistance indices of oa , cra , pcas , and optic nerve diameter are shown in fig . 1 and table 2 .
the area under the roc curve was 0.928 ( 95% ci [ confidence interval ] : 0.843 , 0.101 ) for optic nerve diameter .
the areas under the roc curves were 0.497 ( 95% ci : 0.306 , 0.688 ) for psv , 0.504 ( 95% ci : 0.314 , 0.695 ) for edv , 0.534 ( 95% ci : 0.345 , 0.722 ) for ri and 0.503 ( 95% ci : 0.311 , 0.695 ) for pi in oa .
psv , edv , ri , and pi of the oa , cra , and pcas covered a similar area .
the edv of the cra and pcas had areas slightly but not significantly larger than that of the other blood flow parameters .
in this study we found no significant difference in psv , edv , or pi of the oa , cra , and pcas between eyes with and without on .
the mean ri in the pca was slightly lower in the eyes with on than in the contralateral eyes .
thickening of the optic nerve results from the inflammation in on and has been described previously .
the observed thickening is likely to be a major cause of the initial loss of visual acuity .
the enlarged optic nerve in on compresses the oa within the optic canal and this compression may contribute to the impairment of orbital hemodynamics . in this study
the ri is angle - independent and provides a good measurement by which to quantify vascular resistance in circulation , particularly in tortuous vessels like the pca .
few studies have performed cdi to assess orbital blood flow velocities and optic nerve diameter in on ; these were usually of limited sample size and the results produced were inconsistent .
the inconsistency may be explained in part by differences in patient characteristics , the cause of on , definitions of on , blood flow velocity measurements and the amount of time elapsed between the acute attack and examination . while differences in hemodynamic parameters over the course of the disease may partly account for the range of results seen in the literature ,
it is much more likely that the main component of variance in on doppler studies results from differences in instrumentation and technique .
large foot - print transducers , in the 7.5- to 10.0-mhz range , with poor lateral resolution , placed directly on the closed eyelid at the orbital ridge while not specifically avoiding the lens will not yield optimal measurements .
evaluated only the resistive indices of the cra ; they found resistive indices increased in the affected side and attributed the difference to nerve swelling and the resultant resistance to flow .
our findings also differ from those of karaali et al . , who found that psv , edv , and ri in the oa are increased in patients with acute on although the velocities and resistive indices of the cra in affected and normal eyes did not differ significantly .
also reported that psv , pi , and ri in the oa are increased in patients with acute on although the edv in affected and normal eyes did not differ significantly .
furthermore , pache et al .   reported a significant reduction in the psv and edv of the oa , pcas , and cra in patients with ms compared with healthy controls .
modrzejewska et al .   also reported statistically significant diminishing blood flow velocity parameters in the eyeball arteries of patients with both ms and on .
they did not observe any changes in vascular resistance indices when compared with the control group .
the absence of abnormalities in vascular resistance could be due to a comparatively long passage of time between the clinical manifestation of on and the study .
reported that in patients with ms , the mean psv , edv , and ri in the oa of eyes with on were not significantly different from those in unaffected fellow eyes and healthy control eyes .
the mean edv in the cra was lower and the mean resistivity indices in the cra and pca were higher in eyes with on than in control eyes .
they found that orbital hemodynamics in all retrobulbar vessels did not significantly differ from normal controls in patients with compressive , inflammatory , toxic or hereditary optic neuropathy .
our findings indicate that optic nerve diameter is the most reliable and practical predictor of on .
the pathophysiology of on has not been fully described , but thickening of the nerve in association with demyelination and inflammation may compress the blood vessels within the optic canal .
alternatively , vasospasm due to an increased plasma level of endothelin-1 , a potent vasoconstrictor , may result in vasospasm and vascular dysregulation .
this could cause an increase in resistance to flow in the artery and through ischemia lead to eventual exoplasmic stasis and visual loss .
evaluation with gray - scale sonography of the optic nerve and cdi of orbital hemodynamics in patients with acute on , combined with proof of decreased ri in pcas may facilitate an accurate diagnosis .
one limitation of this study is that blood flow measurements were only performed in the contralateral eyes of the patients without an additional control group . however , as values of orbital blood flow velocity are variables within the healthy population , any differences in values between the orbit affected by on and the unaffected orbit are highly significant .
use of the contralateral eye as an internal control therefore seems practical since cdi measurement is known to be influenced by cardiac output and the patient 's stress level .
moreover , on swelling may influence cdi readings to an unknown degree independent of changes in blood flow due to the altered scattering properties of tissue .
additionally , akarsu et al .   demonstrated that there was a similarity in blood flow velocities between contralateral unaffected eyes and healthy control eyes .
the patients in our series were under 50 years old , an age at which glaucoma is uncommon and intraocular pressure was normal in all patients .
an experimental study by guthoff et al .   showed that an increase in intraorbital pressure leads to a decrease in cra flow .
great care was thus taken to apply as little pressure as possible to the patient 's eye during cdi examination .
even though the study included the thorough examination of 23 pairs of eyes , the findings should be interpreted with caution due to the relatively small sample size .
although we have not carried out any special reliability studies , cdi measurements of the eye vessels   and between the right and left eyes   have been shown to be reproducible over time . in conclusion ,
our findings indicates that gray - scale sonography is a non - invasive and repeatable diagnostic method , which reveals significant optic nerve thickening on the side affected by on and could play a role in disease diagnosis .
no unilateral differences were observed in the average psv , edv , ri , or pi of the oa and cra .
the reduced ri in pcas may indicate disturbances in retinal and choroidal circulation in patients with on .
further studies with larger groups of patients are needed with age- and sex - matched control groups in order to better understand the role of retrobulbar hemodynamics in the pathogenesis of on .
 purposeto evaluate orbital blood flow velocities and optic nerve diameter with doppler and gray - scale sonography in patients with acute unilateral optic neuritis ( on).methodsorbital doppler and gray - scale sonography was performed in 46 eyes of 23 patients aged 19- to 47-years with acute unilateral on . on was diagnosed by an ophthalmologist on the basis of clinical presentation , presence of decreased visual acuity and assessment of visual evoked potentials . 
 the peak systolic velocity ( psv ) and end - diastolic velocity ( edv ) , as well as the resistance index ( ri ) and pulsatile index ( pi ) of the ophthalmic artery ( oa ) , central retinal artery ( cra ) , posterior ciliary arteries ( pcas ) and optic nerve diameter were measured in both eyes . 
 we compared results from affected and unaffected eyes using the paired t - test . 
 the area under the receiver operating characteristic ( roc ) curves was used to assess the diagnosis of on based on measured blood flow parameters of the oa , cra and pcas and optic nerve diameter.resultsthe mean ( standard deviation ) optic nerve diameter in eyes with on was 4.1 ( 0.8 ) mm , which was significantly larger than the 3.0 ( 0.4 ) mm diameter measured in unaffected control eyes ( p < 0.001 ) . 
 there were no differences in average psv , edv , ri , or pi of the oa and cra between affected and unaffected eyes ( p > 0.05 ) . 
 the mean ri in the pcas was slightly lower in the eyes with on than in the contralateral eyes ( 0.60 vs. 0.64 , p < 0.05 ) . 
 the area under the roc curves indicated that optic nerve diameter was the best parameter for the diagnosis of on.conclusionsoptic nerve diameter was related to on , but orbital blood flow parameters were not . 
Materials and Methods
Patients
Ascertainment of optic neuritis
Sonography
Statistical analysis
Results
Discussion