Effect of nocturnal blood pressure reduction on circadian fluctuation of mean ocular perfusion pressure: a risk factor for normal tension glaucoma

PURPOSE: To study blood pressure (BP), intraocular pressure (IOP), and mean ocular perfusion pressure (MOPP) in patients with untreated normal tension glaucoma (NTG), and to investigate the relationship between circadian MOPP fluctuation and visual field status at initial presentation. METHODS: IOP and BP were evaluated in hospital over 24 hours in 132 patients with NTG, with measurements taken every 2 hours between 12 PM and 10 AM the following day, except for the period between 12 and 6 AM, during which measurements were taken every 3 hours. MOPP was calculated from the 24-hour IOP and BP data. Patients were classified into three groups-nondippers, dippers, and overdippers-corresponding to the degree of reduction in their nocturnal mean arterial pressure (MAP) compared with their diurnal MAP. IOP and systemic and ocular hemodynamic parameters were compared among the groups. The correlations between circadian MOPP fluctuation and visual field scores (mean deviation [MD] and corrected pattern standard deviation [CPSD]) at initial presentation were analyzed. RESULTS: Forty-one (31.1%) of the patients with NTGs were classified into the nondipper group, 36 (27.2%) into the dipper group, and 55 (41.7%) into the overdipper group. Marked circadian MOPP fluctuation was noted in the overdipper group (P < 0.05). Circadian MOPP fluctuation showed positive associations with visual field indices at initial diagnosis of NTG (P < 0.05, R2 = 0.056 with MD, R2 = 0.038 with CPSD). CONCLUSIONS: Marked circadian MOPP fluctuation was associated with nocturnal BP reduction. Circadian MOPP fluctuation may be a risk factor for the development of NTG.     

Circadian changes of intraocular pressure and ocular perfusion pressure after timolol or latanoprost in Caucasians with normal-tension glaucoma

Purpose To evaluate the circadian effects on intraocular pressure (IOP) and ocular perfusion pressure (OPP) of 0.5% timolol or 0.005% latanoprost in Caucasian patients affected by normal-tension glaucoma (NTG). Patients and methods In this crossover trial, 30 consecutive NTG subjects underwent three 24-hour assessments of IOP, blood pressure (BP), heart rate (HR), and OPP [calculated according to the formula OPP = (1/3 systolic BP + 2/3 diastolic BP) x 2/3 – IOP]: at baseline, and after 1-month treatment with timolol or latanoprost. These parameters were recorded at 4 a.m., 8 a.m., noon, 4 p.m., 8 p.m., and midnight. Results Both timolol and latanoprost reduced IOP (p < 0.001), with a difference in favour of latanoprost of 1.3 mmHg (95% CI 0.9, 1.6; p < 0.001). After timolol, BP and HR decreased with respect to baseline (p < 0.001). Latanoprost increased mean OPP (3.6 mmHg, 95% CI 2.9, 4.3; p < 0.001), whereas timolol did not improve it. Conclusions Latanoprost induces an IOP reduction greater than timolol, also achieving a better circadian flattening of the IOP curve. Only latanoprost significantly increased mean 24-hour OPP. The management of Caucasian NTG patients should be critically realized, considering the 24-hour influence of each IOP-lowering drug on the ocular blood perfusion.     

眼灌注压波动对青光眼患者病情的影响

目的：探讨眼灌注压波动对青光眼患者病情的影响。

方法：选取我院2013-01/2015-06收治的40例原发性开角型青光眼患者为观察组,同期我院患者家属40例为对照组。监测受试者24h的眼压、血压与眼灌注压的昼夜波动情况,得出收缩期眼灌注压(SOPP)、舒张期眼灌注压(DOPP)和平均眼灌注压(MOPP)。采用Pearson线性相关性分析MOPP昼夜波动与杯盘比、视野平均缺失(MD)及图形标准差(PSD)的相关性。

结果：观察组患者全天和夜间的MOPP、SOPP和DOPP波动均大于对照组(P<0.05)。MOPP 昼夜波动与MD存在显著的负相关(r=-0.389,95%CI：-0.612～-0.082; P=0.011); 与PSD呈正相关(r=0.512,95%CI：0.139～0.782; P=0.008); 与垂直杯盘比之间无相关性(r=0.115,95%CI：0.056～0.369; P=0.355)。

结论：原发性开角型青光眼患者眼灌注压波动可反映病情的严重程度,可能会导致疾病向严重方向发展,因此通过行24h的灌注压的监测可帮助我们了解原发性开角型青光眼患者全天的眼部血流状态,了解病情发展。     

Relative change in diurnal mean ocular perfusion pressure: a risk factor for the diagnosis of primary open-angle glaucoma

PURPOSE: To investigate diurnal change and pattern of variation in intraocular pressure (IOP) and systolic (SBP) and diastolic (DSP) blood pressures in a group with untreated primary open-angle glaucoma (uPOAG) and compare it with an age-matched, normal group. METHODS: IOP, SBP, and DBP were measured in 14 patients with uPOAG and in 14 normal subjects, every hour between 7 AM and 10 PM and the mean ocular perfusion pressure (MOPP) was calculated. Mixed-effect linear models were used to analyze the repeated-measures data in which both fixed and random effects were included. The relative diurnal change was calculated as the percentage decrease from maximum. RESULTS: The uPOAG group had the higher IOP (P < 0.001) and lower MOPP (P = 0.025). There was a significant diurnal change in IOP, SBP, DBP, and MOPP in both groups (P < 0.001). The pattern of diurnal variation in IOP (P = 0.137), SBP (P = 0.569), and DBP (P = 0.937) was not significantly different between groups but was significantly different for MOPP (P = 0.040). MOPP and IOP were most similar at 7 AM and 1 PM. Postprandial hypotension was significant for SBP, DBP, and MOPP (P < 0.001), but not IOP (P = 0.388) in both groups. The relative change in MOPP was larger in the uPOAG group (38% vs. 26%, P < 0.001), but the change in IOP was similar (42% vs. 41%, P = 0.786). There was a significant effect of DBP on IOP over the course of the day in the uPOAG group (P = 0.011) but not in the normal group (P = 0.733). CONCLUSIONS: The relative diurnal change in IOP was similar in both uPOAG and normal subjects but MOPP showed a significant difference. MOPP significantly decreased after lunch, and was at its lowest in uPOAG at 7 AM, when IOP was at its highest. A significant association was found between diurnal DBP and IOP in uPOAG.     

Retrobulbar hemodynamics in normal-tension glaucoma with asymmetric visual field change and asymmetric ocular perfusion pressure

PURPOSE: To investigate retrobulbar hemodynamics by means of color Doppler imaging in normal-tension glaucoma with asymmetric visual field change and asymmetric ocular perfusion pressure. METHODS: Forty-nine consecutive patients who met the enrollment criteria were enrolled in a prospective study. We measured intraocular pressure at 2-hour intervals for 24 hours and performed color Doppler imaging of the orbital arteries, 48-hour ambulatory blood pressure monitoring, and visual field testing. Color Doppler parameters were compared between subjects with higher ocular perfusion pressure in the eye that had a better mean deviation (concordant group) and worse mean deviation (discordant group). RESULTS: In the eyes with the better mean deviation, the end-diastolic velocity of the ophthalmic artery was significantly slower in the discordant group (P=.0145), while in the eyes with the worse mean deviation, the peak systolic and end-diastolic velocities of the ophthalmic artery were significantly slower and the resistance index of the ophthalmic artery was significantly higher in the discordant group (P=.0395, P=.0088, and P=.0324, respectively). In the concordant group, the end-diastolic velocity of the central retinal artery was slower in eyes with a worse mean deviation. CONCLUSION: Retrobulbar hemodynamics are significantly altered in patients with normal-tension glaucoma who have better ocular perfusion pressure in the eye that has a worse mean deviation.     

Changes in intraocular pressure and ocular perfusion pressure after latanoprost 0.005% or brimonidine tartrate 0.2% in normal-tension glaucoma patients

OBJECTIVE: To evaluate and compare the effects of latanoprost 0.005% once daily and brimonidine tartrate 0.2% twice daily in patients with normal-tension glaucoma (NTG). DESIGN: A randomized, open-label, crossover study. PARTICIPANTS: Twenty-eight NTG patients with progressive visual field defects/optic disc excavation, new disc hemorrhage, or field defects that threatened fixation. INTERVENTION: Patients were randomly allocated to one of two groups. Patients in group 1 were treated with latanoprost, lubricant, and brimonidine for 4 weeks each, whereas patients in group 2 were treated with brimonidine, lubricant, and latanoprost for 4 weeks each. MAIN OUTCOME MEASURES: Intraocular pressure (IOP), pulse rate, and blood pressure were measured at 8 am, 12 noon, and 4 pm after each 4-week treatment. Ocular perfusion pressure (OPP) was calculated. RESULTS: Latanoprost and brimonidine reduced the average IOP by 3.6 +/- 1.9 mmHg (P < 0.001) and 2.5 +/- 1.3 mmHg (P < 0.001), respectively, with a significant difference between the two regimens (P = 0.009). Both drugs significantly reduced IOP at each time point. Latanoprost decreased IOP significantly more than did brimonidine at 8 am (11.7 +/- 2.2 mmHg vs. 13.7 +/- 2.1 mmHg, P = 0.004) and 4 pm (11.4 +/- 2.1 mmHg vs. 13.2 +/- 2.9 mmHg, P = 0.004), but IOP was equal between the two agents at 12 noon (11.5 +/- 2.6 mmHg vs. 11.5 +/- 2.3 mmHg, P = 0.967). IOP was maintained at 12 mmHg or lower in 18 (66.7%) of 27 patients after treatment with latanoprost and in 9 (33.3%) of 27 patients after treatment with brimonidine. Latanoprost monotherapy reduced IOP by 30% in 8 patients (29.6%), but brimonidine monotherapy did not reduce IOP by that much in any of the patients. OPP increased after latanoprost treatment (P < 0.001) but did not increase after brimonidine treatment (P = 0.355). There was no significant change in pulse rate or blood pressure. CONCLUSIONS: Both latanoprost and brimonidine reduce IOP in NTG patients. Brimonidine has a peak IOP-lowering effect equal to that of latanoprost but produces a higher mean diurnal IOP than does latanoprost because of its shorter effect. Latanoprost might favorably alter optic disc blood perfusion by increasing OPP.     

Disk hemorrhage is a significantly negative prognostic factor in normal-tension glaucoma

PURPOSE: We investigated the relationship between disk hemorrhage in normal-tension glaucoma and the progression of visual field defects and, additionally, whether hemorrhage plays a role in the pathogenic process of the chronic disease.METHODS: We retrospectively reviewed the charts of 70 patients with normal-tension glaucoma (mean follow-up, 5.6 years) who were not medicated for glaucoma, and we applied a regression analysis of survival data based on the Cox proportional hazards model. Several clinical factors were investigated to find a possible association with the progression of glaucomatous visual field defined by two different definitions: one by mean deviation change and the other by glaucoma change probability analysis.RESULTS: Disk hemorrhage, corrected-pattern standard deviation, age, systolic blood pressure, and pulse rate had a significant influence on the visual field defect. The cumulative probability of progression of visual field loss was significantly greater for patients with disk hemorrhage than for patients without disk hemorrhage by either criterion for progression (P 相似文献   

原发性开角型青光眼患者不同体位眼灌注压昼夜波动趋势分析

Objective To characterize the circadian fluctuation of ocular perfusion pressure (OPP) in different position  in patients with newly diagnosed, untreatedprimary open-angle glaucoma（POAG）. Design Cohort study. Participants Nineteen patients with POAG (19 eyes) and eighteen healthy controls (18 eyes) were included in the Peking University Shenzhen Hospital. Methods POAG patients and healthy controls were included and underwent 24-hour monitoring of IOP and blood pressure. On 10:00, 14:00, 18:00 and 22:00 o’clock in the daytime, all the subjects were monitored in sitting position, then POAG patients were monitored again after lying down for 5 minutes. On 2:00, 5:00 and 7:00 o’clock at night all the subjects were monitored in supine position, then POAG patients were monitored again after sitting for 5 minutes. Calculating the mean ocular perfusion pressure (MOPP), the systolic ocular perfusion pressure (SOPP) and diastolic perfusion pressure (DOPP) by the formula and analyzing the data. Main Outcome Measures  MOPP, SOPP, DOPP. Results In both groups of habitual position (sitting position in day and supine position in night), the nocturnal MOPP, SOPP and DOPP were lower than diurnal. In both groups, the nocturnal MOPP was lower than diurnal in habitual position (POAG group t=4.092, P=0.000; healthy group t=4.513, P=0.000). However, there was no obvious difference between those two groups (t=-0.973, P=0.350). POAG group had higher 24-hour fluctuation of MOPP (t=2.204, P=0.039), higher nocturnal fluctuation of SOPP (t=3.097, P=0.018), higher nocturnal and 24-hour fluctuation of DOPP than healthy group, all the differences had statistical significance (all P<0.05).  In POAG group , there was no statistical difference between the nocturnal MOPP and the diurnal MOPP in sitting position or in supine position of 24 h (all P>0.05). POAG group had higher 24-hour mean MOPP in sitting position than in supine position, the difference had statistical significance (t=4.306, P=0.001).  Comparing the MOPP of  POAG group  in habitual position with in sitting position of 24 h, there was no statistical difference(t=-2.101, P=0.080). However, POAG group had higher 24-hour mean MOPP in habitual position than in supine position of 24 h, the difference had statistical significance (t=2.707, P=0.035). Conclusions There circadian fluctuation of  OPP in different position in POAG pations can not be treated as the same. The nocturnal MOPP  was lower than diurnal in habitual position, but there was no obvious difference in the 24h-sitting position and 24h-supine position.  (Ophthalmol CHN, 2017, 26: 20-25）     

POAG患者习惯性体位眼压及眼灌注压昼夜波动趋势的研究

目的：探讨初诊未行治疗的原发性开角型青光眼( prilary open angle glaucola,POAG)患者习惯性体位眼压及眼灌注压(ocular perfusion pressure,OPP)波动趋势,并验证由日间平均坐位及卧位眼压推导夜间峰值眼压的可行性。
　　方法：选取POAG患者19例19眼及正常对照组18例18眼,分别于10：00,14：00,18：00及22：00时行坐位眼压及血压监测,为验证由日间卧位眼压推导夜间峰值眼压的可行性,另对POAG组于卧位5 lin后再行监测。2：00,5：00及7：00行卧位监测,计算出OPP并行数据分析。由已知公式通过日间眼压计算夜间峰值眼压,并与实际值对比。
　　结果：24h习惯性体位下,POAG患者平均眼压及眼压波动均高于正常对照组(P<0.05),POAG组平均眼压峰值出现于凌晨5：00,对照组则为7：00。两组夜间眼压均值均大于日间,差异有统计学意义(P<0.05)。两组内习惯性体位平均眼灌注压( MOPP )均表现为夜间低于日间( P<0.05),而两组间 MOPP 无明显统计学差异( P>0.05)。POAG患者MOPP波动较对照组大,差异有统计学意义( P<0.05)。由两公式推导所得夜间眼压峰值均与所测值无明显统计学差异(P>0.05)。
　　结论：习惯性体位下POAG组及正常人的眼压峰值多出现在凌晨至上午,POAG患者的习惯性体位平均眼压及眼压波动均高于对照组。两组内夜间灌注压均较日间低,且POAG患者有更大的MOPP波动。由日间眼压推导夜间峰值眼压具有一定的可行性。     

Prolonged retinal arteriovenous passage time is correlated to ocular perfusion pressure in normal tension glaucoma

BACKGROUND: The pathogenesis of normal tension glaucoma (NTG) might be related to impaired autoregulation of ocular blood flow. The purpose of the study is to evaluate retinal haemodynamics by fluorescein angiography and to correlate arteriovenous passage times (AVP) with ocular perfusion pressure in patients with NTG and controls. METHODS: Thirty-five patients with NTG without any topical treatment (mean age 53 +/- 11 years) and 35 age-matched controls (mean age 53 +/- 11 years) were included in this study. Retinal AVP was assessed by video fluorescein angiography using a scanning laser ophthalmoscope (Rodenstock, Germany). Dye dilution curves of temporal superior and inferior arterioles and venules were evaluated by digital image analysis. AVP was correlated to mean arterial blood pressure and ocular perfusion pressure. RESULTS: The AVP was significantly prolonged in patients with NTG compared to controls (1.82 +/- 0.57 versus 1.42 +/- 0.46, p = 0.002). Patients with NTG and controls showed no significant differences in intraocular pressure, mean arterial pressure and mean and diastolic ocular perfusion pressure. The AVP was significantly correlated to mean arterial pressure and mean and diastolic ocular perfusion pressure in patients with NTG (r = -0.54; p = 0.0006, r = -0.51; p = 0.002, r = -0.49, p = 0.002), but not in controls (r = -0.21; p = 0.23, r = -0.19; p = 0.27, r = 0.02, p = 0.93). CONCLUSIONS: Patients with NTG exhibit prolonged retinal AVP compared to controls. A significant correlation of retinal haemodynamics to mean arterial blood pressure and ocular perfusion pressure might reflect impaired autoregulation in NTG.     

The complex interaction between ocular perfusion pressure and ocular blood flow – Relevance for glaucoma

Glaucoma is an optic neuropathy of unknown origin. The most important risk factor for the disease is an increased intraocular pressure (IOP). Reducing IOP is associated with reduced progression in glaucoma. Several recent large scale trials have indicated that low ocular perfusion pressure (OPP) is a risk factor for the incidence, prevalence and progression of the disease. This is a strong indicator that vascular factors are involved in the pathogenesis of the disease, a hypothesis that was formulated 150 years ago. The relation between OPP and blood flow to the posterior pole of the eye is, however, complex, because of a phenomenon called autoregulation. Autoregulatory processes attempt to keep blood flow constant despite changes in OPP. Although autoregulation has been observed in many experiments in the ocular vasculature the mechanisms underlying the vasodilator and vasoconstrictor responses in face of changes in OPP remain largely unknown. There is, however, recent evidence that the human choroid regulates its blood flow better during changes in blood pressure induced by isometric exercise than during changes in IOP induced by a suction cup. This may have consequences for our understanding of glaucoma, because it indicates that blood flow regulation is strongly dependent not only on OPP, but also on the level of IOP itself. Indeed there is data indicating that reduction of IOP by pharmacological intervention improves optic nerve head blood flow regulation independently of an ocular vasodilator effect.     

Diurnal variation of intraocular pressure in normal-tension glaucoma

PURPOSE: Measurement of diurnal variation of intraocular pressure(IOP) is important for precise diagnosis of normal-tension glaucoma(NTG). We studied diurnal variation of IOP of NTG using a self-measuring tonometer. METHODS: A total of 159 patients(318 eyes) who were diagnosed as having NTG in Osaka Koseinenkin Hospital between 1994 and 2002 measured their own diurnal variation of IOP at home every 3 hours (8 times a day) using a prototype self-measuring non-contact air-puff tonometer(Hometonometer). RESULTS: The maximum IOP, the minimum IOP, and the range of diurnal variation of IOP were 16.8 +/- 2.0 mmHg(mean +/- standard deviation), 12.8 +/- 1.7 mmHg, and 4.0 +/- 1.3 mmHg, respectively. Maximum IOP occurred most frequently at noon(24.3%), 9:00 am(21.4%), and 6:00 am(17.4%). In 69.2% of eyes, maximum IOP was found during outpatient clinic hours(9:00 am to 6:00 pm). Minimum IOP occurred most frequently at midnight(34.1%), 3:00 am(22.8%), and 9:00 pm(17.8%). CONCLUSIONS: Approximately 30% of NTG patients have maximum IOP outside of outpatient clinic hours, and therefore measuring IOP in the early morning is important for determining the precise diurnal variation of their IOP. We hope that a safe self-measuring tonometer with which patients can measure their own IOP will be come commercially available soon, so that we can provide them with more individualized glaucoma treatment using the appropriate combination of medicines.