we recruited patients who were initially diagnosed with ntg at seoul national university hospital glaucoma clinic from september 2007 to march 2009 .
ntg was diagnosed based on clinical and visual field evaluations as well as glaucomatous optic nerve changes with corresponding visual field defects and a peak iop of less than 22 mmhg .
patients diagnosed with ntg were admitted overnight and underwent circadian bp and iop measurements as described below . for unilateral ntg , the affected eye was evaluated ; in bilateral ntg , we evaluated a randomly selected eye .
those patients with a previous or current history of anti - glaucoma medication use , severe heart or renal failure causing hemodynamic instability or any other ocular disease that might cause visual field loss and peak iop exceeding 22 mmhg during a hospitalized circadian iop measurement and subsequently lead to the diagnosis of primary open angle glaucoma ( poag ) were excluded from this study . during the same time period , we recruited a control group of age- and gender - matched patients who were not diagnosed with glaucoma but who had been admitted to kangbuk samsung hospital for cataract surgery .
iop was adjusted by 2.5 mmhg for every 50 m that deviated from 525 m .
all procedures conformed to the declaration of helsinki , and our study was approved by the institutional review board of the clinical research institute .
ntg patients were admitted in the afternoon ( between 1 and 2 pm ) , and they underwent bp and iop measurements at 3 , 5 , 7 , 9 , and 11 pm ; 1 , 7 , 9 , and 11 am ; and at 1 pm the following day .
systolic blood pressure ( sbp ) and diastolic blood pressure ( dbp ) measurements was taken using an automated bp monitor ( pa350 ; mediana , wonju , korea ) placed on the patient 's upper arm after at least three minutes of rest .
iop was subsequently measured using goldmann applanation tonometry three times alternatively for each eye , and the average of the three values was recorded as the iop .
control patients were hospitalized in the morning ( at 7 am ) the day before the cataract surgery and underwent bp and iop measurement in the same manner as our ntg patients every two hours until 11 pm .
the 1 am measurement was omitted in the control group to guarantee enough sleep time since most of the patients had cataract surgery scheduled early the next day .
all ntg patients had visual field examinations with the 30 - 2 full - threshold humphrey field analyzer ( carl zeiss ; meditec inc . , dublin , ca , usa ) within two weeks after discharge .
only those patients with reliable results ( false - positive error less than 20% , false - negative error less than 20% and a fixation loss less than 20% ) were included in our study . visual field indices for analysis were mean deviation ( md ) and pattern standard deviation ( psd ) .
mean arterial pressure ( map ) and mean ocular perfusion pressure ( mopp ) were calculated as follows : map = dbp+1/3(sbp - dbp ) ; mopp=2/3map - iop .
the fluctuation of each parameter was defined as the difference between the peak and the trough measurement of each parameter . additionally , we measured the degree of bp reduction during the night or morning using the following indices : nocturnal dip index=(diurnal average map - nocturnal lowest map)/diurnal average map100 ( % ) ; morning dip index=(24-hour average map - morning lowest map)/24-hour average map100 ( % ) .
the nocturnal period was defined as from 8 pm to 6 am the following day , and the diurnal period included the remaining times of the day [ 13 , 21 ] .
ntg patients were divided into three groups according to the degree of morning bp reduction as follows : non - dipper , morning dip index<5% ; dipper , morning dip index 5% but < 10% ; and over - dipper , morning dip index 10% .
spss ver . 15.0 ( spss inc . , chicago , il , usa ) was used for all statistical analyses .
patient demographics and hemodynamic and iop parameters were compared between the ntg and control groups using mann - whitney u test and chi - square tests .
patient demographics , hemodynamic and iop parameters and visual field indices were compared among three ntg subgroups using kruskal - wallis h test and chi - square tests .
we recruited patients who were initially diagnosed with ntg at seoul national university hospital glaucoma clinic from september 2007 to march 2009 .
ntg was diagnosed based on clinical and visual field evaluations as well as glaucomatous optic nerve changes with corresponding visual field defects and a peak iop of less than 22 mmhg .
patients diagnosed with ntg were admitted overnight and underwent circadian bp and iop measurements as described below . for unilateral ntg , the affected eye was evaluated ; in bilateral ntg , we evaluated a randomly selected eye .
those patients with a previous or current history of anti - glaucoma medication use , severe heart or renal failure causing hemodynamic instability or any other ocular disease that might cause visual field loss and peak iop exceeding 22 mmhg during a hospitalized circadian iop measurement and subsequently lead to the diagnosis of primary open angle glaucoma ( poag ) were excluded from this study . during the same time period , we recruited a control group of age- and gender - matched patients who were not diagnosed with glaucoma but who had been admitted to kangbuk samsung hospital for cataract surgery .
iop was adjusted by 2.5 mmhg for every 50 m that deviated from 525 m .
all procedures conformed to the declaration of helsinki , and our study was approved by the institutional review board of the clinical research institute .
ntg patients were admitted in the afternoon ( between 1 and 2 pm ) , and they underwent bp and iop measurements at 3 , 5 , 7 , 9 , and 11 pm ; 1 , 7 , 9 , and 11 am ; and at 1 pm the following day .
systolic blood pressure ( sbp ) and diastolic blood pressure ( dbp ) measurements was taken using an automated bp monitor ( pa350 ; mediana , wonju , korea ) placed on the patient 's upper arm after at least three minutes of rest .
iop was subsequently measured using goldmann applanation tonometry three times alternatively for each eye , and the average of the three values was recorded as the iop .
control patients were hospitalized in the morning ( at 7 am ) the day before the cataract surgery and underwent bp and iop measurement in the same manner as our ntg patients every two hours until 11 pm .
the 1 am measurement was omitted in the control group to guarantee enough sleep time since most of the patients had cataract surgery scheduled early the next day .
all ntg patients had visual field examinations with the 30 - 2 full - threshold humphrey field analyzer ( carl zeiss ; meditec inc . , dublin , ca , usa ) within two weeks after discharge .
only those patients with reliable results ( false - positive error less than 20% , false - negative error less than 20% and a fixation loss less than 20% ) were included in our study . visual field indices for analysis were mean deviation ( md ) and pattern standard deviation ( psd ) .
mean arterial pressure ( map ) and mean ocular perfusion pressure ( mopp ) were calculated as follows : map = dbp+1/3(sbp - dbp ) ; mopp=2/3map - iop .
the fluctuation of each parameter was defined as the difference between the peak and the trough measurement of each parameter . additionally , we measured the degree of bp reduction during the night or morning using the following indices : nocturnal dip index=(diurnal average map - nocturnal lowest map)/diurnal average map100 ( % ) ; morning dip index=(24-hour average map - morning lowest map)/24-hour average map100 ( % ) .
the nocturnal period was defined as from 8 pm to 6 am the following day , and the diurnal period included the remaining times of the day [ 13 , 21 ] .
ntg patients were divided into three groups according to the degree of morning bp reduction as follows : non - dipper , morning dip index<5% ; dipper , morning dip index 5% but < 10% ; and over - dipper , morning dip index 10% .
spss ver . 15.0 ( spss inc . , chicago , il , usa ) was used for all statistical analyses .
patient demographics and hemodynamic and iop parameters were compared between the ntg and control groups using mann - whitney u test and chi - square tests .
patient demographics , hemodynamic and iop parameters and visual field indices were compared among three ntg subgroups using kruskal - wallis h test and chi - square tests .
twenty - four patients were included in the ntg group ( mean age , 49.813.4 years ; 10 males and 14 females ) , and 22 patients were included in the control group ( mean age , 53.113.7 years ; 15 males and 7 females ) .
two patients admitted for bp and iop measurement after initial diagnosis of ntg revealed peak iop values over 22 mmhg , and these patients were excluded from the study .
table 1 summarizes patient demographics and hemodynamic and iop parameters of both ntg patients and normal controls .
six of the 24 patients in the ntg group had hypertension and were under medical management for this condition , while none of the control group patients had underlying hypertension .
there were no significant differences in the hemodynamic parameters between the two groups in terms of mean sbp , mean dbp , mean map , and map fluctuation ( table 1 ) .
we found no definite nocturnal bp dip in either group , but the ntg group showed a prominent morning bp dip .
therefore , we made a new index , the morning dip index , exhibiting the degree of morning bp dip as represented in our methods section .
the ntg group showed a significantly large morning bp dip compared to the control group ( 7.14.2% vs. 3.83.4% , p=0.022 ) fig .
the ntg group usually showed a higher iop level than the control group , but this difference was not statistically significant ( fig . 2 and table 1 ) .
in both groups , the mean iop was low during the nighttime and high during the daytime , especially in the early morning . there were no significant differences in peak iop between the two groups , but the ntg group showed a significantly large iop fluctuation compared to the control group ( 3.91.1 mmhg vs. 3.02.0 mmhg , p=0.040 ) .
the ntg group also showed a lower mopp than the control group at all times , and the difference was statistically significant at 9 am and 7 pm ( fig.1 ) .
however , there were no significant differences in opp between the two groups in terms of mean mopp and mopp fluctuations ( table 1 ) .
the ntg group was subdivided into three groups according to the degree of morning bp dip : non - dipper , dipper and over - dipper groups .
table 2 presents patient demographics , hemodynamic and iop parameters and visual field indices of each subgroup .
morning non - dippers were younger than dippers or over - dippers , but this difference did not reach statistical significance .
there were no significant differences in mean sbp , mean dbp or mean map among the three groups , while the over - dipper group showed a significantly large map fluctuation .
the mean and peak and fluctuation of iop among the subgroups also were not significantly different . while the mean mopp was not significantly different , the mopp fluctuation showed significant differences among the groups .
finally , there were no significant differences in md and psd among the groups ( table 2 ) .
both the ntg and the non - glaucoma control group did not show a significant nocturnal bp dip ( 2.54.7% in ntg , 3.43.7% in control group ) compared to previous studies .
investigated circadian bp patterns using ambulatory blood pressure monitoring in 51 ntg patients and 28 age - matched controls , and their study showed that the mean nocturnal arterial dip was 14.16.4% in ntg patients and 15.98.6% in controls , which was higher than our results , although their method of bp measurement differed somewhat from ours .
several studies have suggested a correlation between nocturnal hypotension and glaucoma [ 5 , 17 , 23 , 24 ] .
others have reported that there are no significant differences in nocturnal bp dips between glaucoma and control groups [ 25 , 26 ] . in our study
, we did not find any significant differences in nocturnal bp dips between the ntg and control groups .
however , ntg patients revealed a marked bp dip during the morning ( 7 am to 11 am ) .
reported that sbp and dbp are low at 7 am and also after lunch ( 1 pm ) in both untreated poag patients and age - matched normal control groups , while mopp showed a significantly different pattern between the two groups .
the minimum mopp in the untreated poag group was recorded at 7 am when iop is at its highest .
therefore , we evaluated the degree of bp dip in the morning compared to the whole day .
the ntg group showed a larger morning bp dip compared to the control group ( 7.14.2% in ntg and 3.83.4% in controls ) , although the mean sbp , dbp and map were similar in the two groups .
the map fluctuation was larger in the ntg group , but it did not reach statistical significance ; there were also no significant differences in mean mopp and mopp fluctuations between the two groups .
therefore , in this study , a larger morning bp dip in ntg patients was not linked to significant map or mopp fluctuations .
however , it is possible that a morning bp dip compromises ocular perfusion status along with the increase in morning iop ; 50% of ntg patients experienced peak iop in the morning .
when the ntg group was divided into three subgroups according to the degree of morning bp dip , over - dippers showed significantly large map and mopp fluctuations compared to non - dippers or dippers .
however , there were no significant differences in visual field indices ( md and psd ) among the three subgroups ( table 2 ) .
these results disagree with previous studies that emphasized the correlation between mopp fluctuations and visual field indices or glaucoma severity [ 18 , 19 ] .
these discrepancies might be due to our study 's small sample size and short follow - up period .
long - term serial follow - up of visual field tests with larger number of cases might reveal the true relationship between mopp or fluctuations between it and visual field indices . in this study
, we measured circadian iop and bp profiles without disturbing nocturnal sleep , and we found that there were no significant differences in nocturnal bp dips between the ntg patients and the normal control group .
however , ntg patients revealed a significant morning bp dip compared to the control group .
our study is the first report that found that ntg patients showed a more prominent morning bp dip than a control group , but it is still inconclusive whether this resulted from undisturbed sleep that is not considered in other studies or if it is just a representation of the hemodynamic instability of ntg patients . further studies with a larger number of patients may clarify the relationship between undisturbed sleep and morning bp dips in ntg patients .
previous studies on circadian bp measurement with ambulatory blood pressure monitoring have shown that bp declines during sleep , reaching a trough level roughly between 2 and 4 am . as we did not measure bp during these hours ,
ntg patients were significantly more likely to have underlying hypertension than members of the control group .
we compared iop parameters ( including mean and peak and fluctuation of iop ) and hemodynamic parameters ( including mean sbp , mean dbp , mean map , map fluctuation , and nocturnal and morning dip indices ) between those with and without hypertension in ntg patients .
we found that there were no significant iop or hemodynamic parameter differences between the two groups ( results not shown ) .
therefore , the significant morning bp dip seen in the ntg group could be attributed more to glaucoma than to hypertension .
regardless of whether bp dips occur at night or in the morning , ocular perfusion status compromise is possible in ntg patients as both morning and night are well known for having the highest iop level .
the morning bp dip might represent the hemodynamic instability of ntg patients and support the vascular theory of glaucoma development . in conclusion
a marked morning bp dip was associated with significantly large map or mopp fluctuations , but it was not associated with visual field indices . long - term and serial follow - up of these patients are needed to further investigate the association between hemodynamic changes and the severity and functional aspects of glaucoma .
 purposeto investigate and compare the circadian pattern of blood pressure ( bp ) , intraocular pressure ( iop ) and mean ocular perfusion pressure ( mopp ) while experiencing undisturbed sleep in normal - tension glaucoma ( ntg ) and non - glaucoma control patient groups.methodstwenty-four eyes from 24 patients diagnosed with ntg and 22 eyes from 22 control group patients were enrolled . 
 systolic bp , diastolic bp and iop were measured every two hours except for the period of time from 1 am to 7 am in the ntg group and from 11 pm to 7 am in the control group over a one - day period . 
 iop and hemodynamic parameters were then compared between the two groups . 
 ntg patients were subdivided according to the degree of morning bp dip and iop , and hemodynamic parameters and visual field indices ( mean deviation and pattern standard deviation ) were also compared among these subgroups.resultsthere were no significant differences in mean systolic bp , mean diastolic bp and mean arterial pressure ( map ) between the ntg and the control groups . 
 the ntg group showed a significantly large morning bp dip compared to the control group ( 7.14.2% vs. 3.83.4% , p=0.022 ) . 
 however , there were no significant differences in mean or fluctuation of mopp between the two groups . 
 morning over - dippers showed significantly large map and mopp fluctuations compared to non - dippers and dippers , while there were no significant differences in visual field indices among the three subgroups.conclusionsntg patients showed significant morning bp dips compared to the control group . 
 the marked morning bp dip was associated with significantly large map or mopp fluctuations but was not associated with visual field indices . 
Materials and Methods
Patients
Measurement of circadian BP and IOP
Visual field examination
Hemodynamic parameters and nocturnal dip and morning dip indices
Statistical analysis
Results
Discussion