| Glaucoma is mainly due to the elevated pathological intraocular pressure (IOP) which leading to characteristic damage of the optic nerve and visual function loss. Early diagnosis and timely detection of progression is the key to glaucoma diagnosis and treatment.IOP is an important risk factor leading to glaucomatous optic neuropathy (GON)[1]. Reducing IOP is a main method to slow down progression of the disease[3-5], and evaluating IOP is an important way to set treatment goals and to indicate the efficacy of treatment[2]. However, IOP is not fixed, if we just rely on a single IOP value measured during working hour so as to diagnose and evaluate the patient’s condition, we can not get a whole picture of the level of IOP. In addition, more and more researchers believe that in order to control the progression of the glaucoma effectively, a sustained IOP below a certain level to maintain the stable environment of the optic nerve is really necessary. So it is valuable to study the relationship between IOP fluctuation and GON. Although the relationship of IOP and GON has been studied, but there are many theories of pathogenesis of glaucoma. Therefore, factors, other than IOP, and their relevance with the GON is also worth further exploration.This study is divided into three parts:In the first part, we will discuss characteristics of24-hour intraocular pressure fluctuation in different type of glaucoma patients (normal tension NTG, high-tension POAG) and explore possible ways of evaluation nocturnal IOP peak; In the second part, we will explore the patterns and differences of24-hour IOP level, and IOP fluctuation of different stage of visual field loss in glaucoma; In the third part, we will analyze the correlation between systemic condition, ophthalmic condition, and24-hour IOP parameters with GON, so as to provide evidence for control of IOP effectively and smoothly. Objective To study IOP level, IOP fluctuation and IOP peak distribution in24-hour and different time period of untreated NTG and POAG patients as well as compare their differences, so as to understand the pattern of24-hour IOP fluctuation in different types of glaucoma, and the necessity for24-hour IOP monitoring. And to explore the possibility to estimate nocturnal peak IOP with office hour or diurnal IOP level, so as to provide a basis for clinical diagnosis and treatment.Methods121patients with primary open-angle glaucoma (242eyes) meeting the inclusion criteria, were admitted to hospital to have24-hour IOP monitoring with a non-contact tonometer (NIDEK, Japan). The patients go to bed after10PM. During12AM-6AM, the patients were awaken and taken IOP measurement instantly in sitting position. Office hour is from8AM to4PM (5points), diurnal is from8AM to10PM (8points), and nocturnal is from12AM to6AM. And the patients measured central corneal thickness (CCT), axial length (AL) and had central visual field test. And according to peak IOP value after correcting, we divided all the patients into POAG group (>21mmHg) and NTG group (<21mmHg). GON is evaluated according to optic nerve longitudinal cup-disc ratio (CD ratio) morphologically and Glaucoma staging system2(GSS2) functionally. With each time point average IOP, we draw24-hour IOP curve, and then compare IOP fluctuation in24hours and each time period of NTG and POAG by independent T test. We also analyze peak IOP distribution. Finally, using Pearson correlation analysis and linear regression to evaluation the relationship between nocturnal peak IOP and office or diurnal mean and peak IOP.Results The overall trend of24-hour IOP fluctuation is similar in NTG and POAG patients. IOP reaches peak around6AM to8AM, then declines gradually, and presents a small peak around4PM, after then starts rising gradually from8PM and gets peak again around2AM, which is particularly apparent in POAG patients.The IOP fluctuation range of24-hour is greater than each time period. IOP fluctuation range of24-hour and each time period in POAG is significantly greater than NTG (IOP fluctuation range:24-hour t=4.195P<0.001, office hour t=3.308 P<0.001, diurnal t=4.195, P<0.001, and nocturnal t=4.328P<0.001). But when comparing Range/Mean, there shows no significance (t=0.613P=0.54) between two groups. Further24-hour IOP fluctuation range is correlated with mean IOP (r=0.487), which means1mmHg rise in mean IOP,0.4mmHg24-hour IOP fluctuation range expanding.In all glaucoma patients, IOP reach peak mainly from8AM to10AM and from12PM to6PM. In NTG group, peak IOP appears mainly from8AM to10AM and from12PM to6AM, the most of which is8AM (29eyes17.47%). Peak IOP appears in the office hour accounting for46.39%, and in nocturnal time accounting for49.40%. In POAG group, the probability of IOP reaching peak is more in night time, mainly from12PM to6AM, followed by8AM-10AM, the most of with is2AM (19eyes25%). Peak IOP appears in the office hour accounting for43.42%, and in nocturnal time accounting for65.79%.If we just use peak IOP during office hours to determine whether the presence of a high-tension glaucoma, POAG, there are only37%eyes having an abnormal IOP (>21mmHg),33%of eyes may be misdiagnosed as NTG. Besides in those whose peak IOP is within normal range,16%and8%of eyes suffering from slight GON functionally and morphologically, separately, and6%of eyes without significant GON functionally and morphologically. Similarly, if we just use peak IOP during diurnal hours to determine whether the presence of a high-tension glaucoma, POAG, there are only47%eyes having an abnormal IOP (>21mmHg),31%of eyes may be misdiagnosed as NTG. Besides in those whose peak IOP is within normal range,10%and7%of eyes suffering from slight GON functionally and morphologically, separately, and5%of eyes without significant GON functionally and morphologically. Those people might be missed, and do not have timely intervention.There shows a good linear correlation coefficient between office hours or diurnal peak and mean IOP with nocturnal peak IOP in POAG and NTG patients. The correlation coefficient is as followed, from strong to weak:diurnal mean IOP(r=0.731), office time mean IOP(r=0.694), diurnal peak IOP(r=0.686) and office time peak IOP(r=0.649). Both NTG and POAG group have a good correlation. Clinically, we can use IOP level in these time periods shown above to estimate nocturnal peak IOP.Conclusions There is a certain rhythm of24-hour IOP fluctuation in NTG and POAG, with similar trend, but having its own characteristics. IOP fluctuation range in POAG is greater than in NTG. However, the difference of IOP fluctuation range between glaucoma patients and normal people and its inner possible mechanism need to be further study. Because IOP fluctuation range of24-hour is greater than each time period and more than50%patients have their peak IOP out of office hour,24-hour IOP monitoring is irreplaceable in clinical work. Clinically, we can use IOP level in office hours or diurnal period to estimate nocturnal peak IOP as reference.Part TwoCharacteristics and differences of24-hour intraocular pressure with different degree of visual field damage in NTG and POAGObjective To compare IOP level and fluctuation pattern in24-hour and each time period of different stage of visual field damage in untreated NTG and POAG patients and explore possible intrinsic link with GON.Methods121patients with primary open-angle glaucoma (242eyes) meeting the inclusion criteria, were admitted to hospital to have24-hour IOP monitoring with a non-contact tonometer (NIDEK, Japan). The patients go to bed after10PM. During12AM-6AM, the patients were awaken and taken IOP measurement instantly in sitting position. Office hour is from8AM to4PM (5points), diurnal is from8AM to10PM (8points), and nocturnal is from12AM to6AM. And the patients measured central corneal thickness (CCT), axial length (AL) and had central visual field test. And according to peak IOP value after correcting, we divided all the patients into POAG group (>21mmHg) and NTG group (≤21mmHg). GON is evaluated according to central visual field test and classified into3groups according to Glaucoma staging system2(GSS2), that is F1early stage (0to1), F2medium stage (2to3) and F3late stage (4to5). With average IOP value at each time point, we draw24-hour IOP curve of different stage of visual field damage in NTG and POAG. We use ANOVA analysis to compare IOP level and fluctuation trend in different visual field damage group, and independent T test to compare IOP pattern between NTG and POAG. Results Different visual field damage groups of all the glaucoma patients show a similar24-hour IOP fluctuation trend, without significant difference in IOP level, but in terms of IOP fluctuation, there shows significant difference (SD P=0.011,24-hour fluctuation range P=0.031), mainly in early stage (SD2.44±0.96mmHg,24-hour fluctuation range7.82±3.14mmHg) compared to medium (SD2.1±0.87mmHg,24-hour fluctuation range6.81±2.73mmHg) and late stage (SD2.04±0.79mmHg,24-hour fluctuation range6.8±2.56mmHg)(SD P=0.014, P=0.020, respectively,24-hour fluctuation range P=0.020, P=0.029, respectively).In NTG patients, IOP fluctuation range in early stage is greater than medium and late stage, especially from8AM to8PM. The trend of IOP fluctuation in early stage is different from medium and late stage. While, the trend of IOP fluctuation medium and late stage is similar, but overall IOP level in medium stage is greater than late stage (24-hour mean IOP P=0.012, peak IOP P=0.003, valley IOP P=0.011). In terms of IOP fluctuation range,24-hour IOP SD and nocturnal IOP fluctuation range of three groups show significant difference (P=0.036and P=0.017, respectively), and occur mainly between the early and late stage (SD P=0.010, nocturnal IOP fluctuation range P=0.004).In POAG patents,24-hour IOP fluctuation trend in different stage of visual field damage is similar. But there is a significant rise of nocturnal IOP in early stage, with significant difference of nocturnal mean IOP between early with medium, and early with late stage (P=0.033and P=0.049, respectively). Nocturnal mean IOP in early stage is higher than medium or late stage (Nocturnal mean IOP:early stage20.11+3.88, medium stage18.24±2.96, late stage18.39±2.79). As for IOP fluctuation, no significant differences among the three groups are shown.When comparing NTG and POAG patients of different visual field damage stage, two groups show significant different in mean IOP, peak IOP, valley IOP, SD, IOP fluctuation range (P<0.001), apart from office hour IOP fluctuation range in medium stage. POAG patients show a higher IOP level and fluctuation In addition, IOP changes after falling asleep in NTG and POAG patients have significant difference (IOP mean change t=3.529P<0.001、IOP peak change t=2.172P=0.032、IOP valley change t=3.522P=0.005), that is IOP changes in POAG are greater than in NTG, and this difference is mainly between early stage of NTG and early stage of POAG(IOP mean change t=3.874P,0.001、IOP peak change t=2.598P=0.032、IOP valley change t=4.657P=0.005), while medium and late stage of NTG and POAG without significant difference.Conclusions There is some certain regularity of24-hour IOP fluctuation change in NTG and POAG patients, but they have different characteristics. But those with advanced visual field damage, their IOP level and fluctuation are not necessarily great. There are differences in the different stage of visual field damage, especially in early stage between medium and late stage, which indicates us the factors leading to GON could be different between NTG and POAG. So those factors, other than IOP, which might lead to pathological IOP fluctuation and could correlated with GON need to be further studied.Part ThreePossible correlated factors with glaucomatous optic neuropathy in NTG and POAGObjective By analyzing the correlation between systemic, ophthalmic conditions and24-hour IOP levels, fluctuation and related parameters with GON in NTG and POAG patients, to explore relevant factors with GON and provide recommendations for early clinical diagnosis and treatment.Methods121patients with primary open-angle glaucoma (242eyes) meeting the inclusion criteria, were admitted to hospital to have24-hour IOP monitoring with a non-contact tonometer (NIDEK, Japan). The patients go to bed after10PM. During12AM-6AM, the patients were awaken and taken IOP measurement instantly in sitting position. Office hour is from8AM to4PM (5points), diurnal is from8AM to10PM (8points), and nocturnal is from12AM to6AM. And the patients measured central corneal thickness (CCT), axial length (AL) and had central visual field test. Besides, their systemic and ophthalmic conditions were also analyzed, including gender, age, diabetes, high blood pressure, smoking, family history and refraction condition After correcting the IOP value, the following IOP parameters will be analyzed:IOP level (mean, peak and valley IOP), IOP fluctuation (SD, Range, Peak to mean), IOP level and IOP fluctuation range changes after sleep, and IOP stability (Times above mean IOP, time points above mean IOP, area under the curve above mean IOP and increasing speed of IOP). GON is evaluated according to optic nerve longitudinal cup-disc ratio (CD ratio) morphologically and Glaucoma staging system2(GSS2) functionally. Continuous variables use Pearson correlation analysis and linear regression, and categorical variables use Spearman correlation analysis. Partial correlation analysis is used to the correction variables. For those relevant factors, logistic regression or linear regression analyze is used.Results Our study found that the age (OR=1.03395%CI1.010～1.057), the refraction condition (OR=0.83395%CI0.708～0.980), central corneal thickness (OR=0.987,95%CI0.979to0.996), smoking (CD ratio r=0.231P=0.044, GSS2r=0.211P=0.009) is positively correlated with GON especially in NTG.In newly diagnosed and untreated NTG and POAG patients with different severity of GON, IOP level and IOP fluctuation parameters are not found correlated with GON or any possibility to increase the risk of advanced vision field damage. Only in POAG patients, after corrected mean IOP, the diurnal IOP fluctuation range reveals positively correlated (r=0.231P=0.037) with CD ratio. In NTG patients, with1mmHg increasing in valley IOP change after sleep, the risk for advanced vision field damage may increase by23.5%.GON is also related to the stability of IOP fluctuation, especially in POAG patients. The maximum rate (Rmax) and average rate (Rmean) of IOP rising are positively correlated with CD ratio in POAG patients (Rmax r=0.26P=0.020Rmean r=0.284P=0.010). With10units increasing of Rmax, the possibility of CD ratio could enlarge by0.1～0.2(r=0.250P=0.020).Conclusions Age, smoking, central corneal thickness, and myopia are associated with GON, so we need to pay more attention to diagnosis, treatment and follow-up of these patients with those factors clinically. IOP level, fluctuation and rate of change have some certain correlation with POAG patients, so we need to actively control IOP level, fluctuation and rate of change. As for NTG patients, our study support the treatment strategy of controlling nocturnal IOP level. Furthermore, factors, other than IOP, that might cause advanced GON should catch our attention and need further study. |
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