The Correlation Between Juvenile Ocular Hypertension And Autonomic Nervous System Function

Ocular hypertension (OHT) is intraocular pressure higher than normal in the absence of optic nerve damage or visual field loss. Current consensus in ophthalmology defines normal intraocular pressure (IOP) as that between10mmHg and21mmHg. Elevated IOP is the most important risk factor for glaucoma, so those with ocular hypertension are frequently considered to have a greater chance of developing the condition.Nowadays, some juveniles or adolescences with unstable IOP were often referred in clinical practice, which is more occurred in teenage; IOP frequently fluctuated and increased even exceeds30mmHg by Goldmann applanation tonometry (GAT) but no any disturbance symptoms of eye feeling and visual acuity. There was no any pathological change of optic nerve damage or visual field loss and as for majority of these cases in long-term follow up, IOPs appeared to decline to average level after the adolescence stage without any medical treatment. This juvenile ocular hypertension (JOHT) is specifically identified as "adolescence IOP fluctuation" or "adolescence ocular hypertension".Currently, clinical practices are generally lacking sufficient knowledge about pathogenesis, influence factors and prognosis of JOHT, thus lead to tremendous formidable challenges towards diagnosis and managements of the disease.The autonomic nervous system (ANS) is the part of the peripheral nervous system that acts as a control system functioning largely below the level of consciousness, and controls visceral functions. The ANS affects heart rate, digestion, respiratory rate, salivation, perspiration, diameter of the pupils, micturition (urination), and sexual arousal. Whereas most of its actions are involuntary, some, such as breathing, work in tandem with the conscious mind. It is classically divided into two subsystems:the parasympathetic nervous system (PSNS) and sympathetic nervous system (SNS).The dynamics of the aqueous humor, which determine the IOP level, is highly controlled by the autonomic nervous system, mainly the sympathetic, regulating its production and parasympathetic controlling the evacuation of aqueous humor. Actually, some studies have demonstrated that ocular hypertension is related with autonomic nervous system dysfunction.Juveniles are in the stage of physical and mental growth, undertaking pressures of heavy school works, their autonomic nervous systems are also under developing progress. Besides, adolescence is also a stage with the obvious fluctuations of sex hormones that might be the possible factors in the pathogenesis of glaucoma.Hence, this study tends to focus on the clinical features and IOP fluctuations, autonomic nervous system status and function, blood catecholamine and sex hormones levels of JOHT, try to work out the clinical features and possible pathogenesis of JOHT so that to facilitate the diagnosis and management of JOHT in clinical practices and moreover, to offer enhanced clinical practice guidance and prognosis of JOHT as well.PartⅠ Analysis on Clinical Features of Juvenile Ocular HypertensionPurpose:To analyze clinical features and IOP fluctuation of juvenile ocular hypertension (JOHT) in order to facilitate the clinical diagnosis of JOHT.Method:Records of follow-up JOHT gathered from outpatients of Department of Ophthalmology, Eye&ENT Hospital, Fudan University, ranging from Mar2010to Mar2012, and healthy volunteers (control) and juvenile onset open angle glaucoma(JOAG) patients with matched sex, age and Body Mass Index (BMI) were enrolled in this study. Goldmann applanation tonometry(GAT), central corneal thickness (CCT) and corneal curvature were examined by individual, accompanied with24-hour IOP measurements in hospital by non-contact tonometer (NCT),2hours a time starting from8am, and the IOP between00:00to06:00am was measured in sitting position immediately after wake up.Results:68eyes of34subjects were included in JOHT, accordingly40eyes of20subjects in the control and24eyes of12subjects in JOAG. GAT of JOHT was26.2±5.2mmHg (21-42mmHg), CCT was574.1±28.1um, corneal curvature was7.87±0.26mm,24-hour average IOP was26.3±5.3mmHg, pe(?) value33.2±6.2mmHg, aggregately appeared at8:00to10:00(44/68, 64.7%, X2=84.452, P=0.000), valley value20.6±5.0mmHg, aggregately appeared at22:00-2:00(47/68,69.1%, X2=46.387, P=0.000), IOP fluctuation was12.6±3.8mmHg; GAT of the control was16.1±3.1mmHg (10-21mmHg), CCT was564±35.3um, corneal curvature was7.89±0.30mm,24-hour average IOP was17.4±3.8mmHg, peak value22.7±5.5mmHg, aggregately appeared at4:00-8:00(20/40,50.0%, X2=18.850, P=0.042), valley value13.2±3.0mmHg, aggregately appeared at18:00-20:00(17/40,40.5%, X2=18.300, P=0.050),IOP fluctuation was9.5±4.8mmHg; GAT of JOAG was24.0±4.1mmHg (18-31mmHg), CCT was559.2±36.3um, corneal curvature was7.80±0.29mm, peak value35.9±9.9mmHg, valley value22.2±7.8mmHg, distributed discretely (X2=6.750and5.000, P=0.564and0.931), IOP fluctuation was13.7±4.3mmHg. Variance of CCT and corneal curvature did not have statistical significance (F=2.102and0.582; P=0.127and0.561). Pearson correlation coefficient showed that CCT, GAT and24-hour average IOP were not statistically significant correlation (r=0.070and-0.016; P=0.587and0.900). Variance of GAT,24-hour IOPs, IOP peak, valley and IOP fluctuation of the three groups were statistically significant (F=49.245,31.683,30.797,25.54and8.252; all P=0.000), IOPs of JOHT and JOAG were similar to each other, both were statistically higher than those of the control (P<0.01). Comparison results of GAT,24-hour IOPs, IOP Peak and valley of JOHT and JOAG in summer and winter respectively were statistically significant (JOHT t=-3.192,-3.56,-2.07,-3.223; P=0.004,0.002,0.049,0.003; JOAG t=-2.887,-4.942,-3.702,-5.004; P=0.034,0.003,0.01,0.002),but only considering variance of IOP fluctuation in summer and winter did not form any statistical significance (t=0.067and-0.204; P=0.947and0.845); Variance of IOPs and fluctuation of control in summer and winter respectively had no statistical significance (t=2.018,-1.102,-0.727,-1.483,0.085; P=0.078,0.296,0.484,0.169,0.934). Following2years’ observation without any medicine, IOPs of4out of34subjects of JOHT declined to below21mmHg (4/34,11.8%),3were diagnosed as JOAG with characteristically glaucomatous optic nerve damage or visual field loss (3/34,8.8%).Conclusions:Average GAT of JOHT is generally above21mmHg, with no statistical correlation of CCT and corneal curvature; peak value of24-hour IOPs appeared to be aggregated in the mornings and valley value in the Part II Study on correlation of Juvenile Ocular Hypertension and Autonomic Nervous System FunctionPurpose:To study the correlation between juvenile ocular hypertension (JOHT) and autonomic nervous system (ANS) function in order to explore the possible pathogenesis of JOHT.Methods:Records of follow-up JOHT gathered from outpatients of Department of Ophthalmology, Eye%ENT Hospital, Fudan University, ranging from Mar2010to Mar2012, and healthy volunteers (control) and juvenile onset open angle glaucoma(JOAG) patients with matched sex, age and Body Mass Index (BMI) were enrolled in this study.24-hour IOP tonometry and24-hour Holter monitoring were performed.NCT was used to measure IOPs2hours a time starting from8am, and the IOP between00:00to06:00am was measured in sitting position immediately after wake up, to calculate24-hour average IOP and IOP fluctuation. Time domain analysis (SDNN, SDANN, RMSSD, pNN50) and frequency domain analysis (LF, HF, TF, and LF/HF) were used in24-hour Holter monitoring to evaluate autonomic nervous system function.Results:34subjects were included in JOHT, accordingly20subjects in the control and12subjects in JOAG. Average IOP/IOP fluctuation of JOHT, the control and JOAG were26.3±5.3mmHg/12.6±3.8mmHg,17.4±3.8mmHg/9.5±4.8mmHg and28.8±8.4mmHg/13.7±4.3mmHg respectively.24-hour average IOP and IOP fluctuation of JOHT and JOAG were quite similar to each other (P=0.120and0.364) and were apparently higher than those of the control, with variance statistically significant (all P=0.000). Variance among average heart rate (HR) of three groups were not statistically significant (P= evenings, fluctuation is obvious, IOPs fluctuated significantly with season changes; in2years without medicine, about11.8%of the subjects can be found IOPs decline to normal level and8.8%grow up to JOHT. 0.812), and the minimum HR of JOAG was statistically lower than that of the control (P=0.046). SDNN, SDANN of JOHT were significantly lower than those of JOAG (P=0.043and0.030), while LF, TP all apparently lower than those of JOAG (P=0.046and0.028) and LF/HF statistically lower than the control (P=0.011). Average HR of three groups and LF/HF were of diurnal variability (P=0.000,0.000,0.011and0.000,0.000,0.016). Diurnal variability of LF of3groups were not statistically significant (P=0.074,0.181,0.328). HF, TP of JOHT and the control were of diurnal variability (P=0.000,0.002and0.000,0.019), while diurnal variation of HF, TP of JOAG appeared to be weaker (P=0.055and0.136). Average HR of JOAG was quite low at day time while LF and LF/HF were quite high at night, variance was statistically significant compared with those of JOHT and the control (P<0.05).24-hour average IOP and LF, LF/HF were of negative correlation (P=0.016and0.023);24-hour IOP of JOHT and LF/HF were of negative correlation (P=0.049). IOP fluctuation and LF, TP were of negative correlation (P=0.017and0.032).Ages and LF, HF and TP were of positive correlation (P=0.001,0.044,0.003); ages of JOHT and LF, TP, LF/HF were of positive correlation (P=0.004,0.015,0.023).Results:LF/HF of JOHT was lower than those of the control, while SDNN, SDANN, LF and TP were lower than JOAG. IOPs, ages and autonomic nervous system function were of correlation, which indicated that the immature autonomic nervous function might play a role in the pathogenesis of JOHT. Part Ⅲ Study on Correlation of Juvenile Ocular Hypertension and Catecholamine HormonesPurpose:To study the correlation between JOHT and blood plasma catecholamine hormones in order to explore possible pathogenesis and influence factors of JOHT.Methods:Records of follow-up JOHT gathered from outpatients of Department of Ophthalmology, Eye&ENT Hospital, Fudan University, ranging from Mar2010to Mar2012, and healthy volunteers (control) and juvenile onset open angle glaucoma (JOAG) patients with matched sex, age and Body Mass Index (BMI) were enrolled in this study.24-hour IOP tonometry and24-hour Holter monitoring were performed. Calculate24-hour average IOP and IOP fluctuation based on24-hour IOP tonometry. Use frequency domain analysis (LF, HF, TF, and LF/HF) to evaluate autonomic nervous system function. Blood plasma catecholamine hormones in setting position after30minutes rest at8am were detected by high performance liquid chromatographic method (HPLC), including dopamine (DA), norepinephrine (NE) and adrenaline (AD).Results:34subjects were included in JOHT, accordingly20subjects in the control and12subjects in JOAG.24-hour average IOP and IOP fluctuation were similar to each other (P=0.120and0.364), all apparently higher than those of the control, variance was of statistical significance (all P=0.000). Average HR of three groups were not statistically significant, and the minimum HR of JOAG was statistically lower than that of the control (P=0.046). LF, TP of JOHT were significantly lower than those of JOAG (P=0.046and0.028), while LF/HF of JOHT was apparently lower than that of the control (P=0.011). DA concentration of blood plasma of JOHT was higher than that of the control and JOAG, but with no statistically significant variance (P=0.807); NE and AD concentration of JOHT were higher than those of the control but lower than JOAG, but with no statistically significant variance (P=0.757and0.278). Blood plasma AD level of all subjects included in the study were of positive correlation with LF (P=0.024).24-hour average IOP and IOP fluctuation of JOHT were of positive correlation with AD level (P=0.027and0.003); LF and AD level were of correlation (P=0.040); average HR and NE level were of correlation (P=0.019).Conclusions:Blood plasma adrenaline level is related with autonomic nervous system function, especially sympathetic nerve activity.24-hour average IOP and IOP fluctuation of JOHT are related with blood plasma AD level, this indicates that JOHT may be influenced by autonomic nervous system function. Part ⅣStudy on Correlation of Juvenile Ocular Hypertension andAdolescence Sex Hormones LevelPurpose:To study juvenile sex hormones level of JOHT in order to explorepossible protection mechanism of optic nerve under high IOP status.Methods;Records of follow-up JOHT gathered from outpatients ofDepartment of Ophthalmology,Eye&ENT Hospital,Fudan University,rangingfrom Mar2010to Mar2012,and healthy volunteers (control) and juvenileonset open angle glaucoma (JOAG) patients with matched sex，age and BodyMass Index (BMI) were enrolled in this study. Calculate24-hour average IOPand IOP fluctuation based on24-hour IOP tonometry. Blood serum sexhormones level at8am on the third day of the female menstrual period wereexamined by radioactive immunoassays (RIA),including estrogen (E),progesterone (P),testosterone (T),no specific testing date criteria for theothers.Results:Blood serum E of JOHT was37.48±43.26pg/mL,blood serum Pwas0.66±1.42ng/L,all significantly higher than those of JOAG (E19.34±15.58pg/mL and P0.580.21ng/L),variance with statistical significance (P=0.045and0.027),blood serum T of JOAG was1.68±2.22ng/mL,significantlyhigher than that of the control (T0.89±1.40ng/mL) while apparently lowerthan that of JOAG (T2.71±1.78ng/mL),variance with statistical significance(P=0.018). Three sex hormones were not statistically correlated with24-houraverage IOP and IOP fluctuation.Conclusions,Blood serum estrogen and progesterone of JOHT are higherthan those of JOAG,which could be the protection mechanism of optic nerveunder high IOP status. And the higher blood serum testosterone may be a...