Relationships among systemic blood pressure, intraocular pressure, and open-angle glaucoma

Several vascular factors, including systemic hypertension (or high blood pressure [HBP]), ocular perfusion pressure, and nocturnal hypotension, have been identified as risk factors for the development and progression of glaucoma. The results of epidemiologic studies of these factors and their relationships to intraocular pressure (IOP) and open-angle glaucoma (OAG) have been contradictory. Inconsistent definitions of HBP and OAG, inconsistent design, and differing population characteristics within these studies have obfuscated definitive conclusions. Here, we review the relationships among blood pressure, IOP, and OAG.     

Determination of individually endurable intraocular pressure (pressure of target) in primary glaucoma

On the basis of ocular perfusion pressure a new method was suggested for determining an individually endurable intraocular pressure (IOP), i.e. pressure of target. A total of 390 eyes (232 patients with primary open-angle and normal-tension glaucoma) were examined before and after conservative and surgical treatment. The pressure of target was found, in a progressing worsening of visual functions, to be significantly lower versus the stabilized glaucoma, which was due to a low ocular perfusion pressure. The maximally tolerable IOP in a progressing glaucomatous optic neuropathy concomitant with a normalized IOP amounts to 13-15 mm Hg; while, in the stabilized glaucoma it can exceed the mean statistic norm. The pressure of target was shown to be a non-permanent value, which changes depending on the dynamics of the ophthalmic perfusion pressure and IOP. The sensitivity of the suggested method is 77.4%. It can be used in prognosticating the glaucomatous-process clinical course and in choosing an optimal tactics for the treatment of open-angle and normal-tension glaucoma.     

Abnormal systemic and ocular vascular response to temperature provocation in primary open-angle glaucoma patients: a case for autonomic failure?

PURPOSE: To assess systemic and ocular vascular reactivity in response to warm and cold provocation in untreated patients with primary open-angle glaucoma and normal control subjects. METHODS: Twenty-four patients with primary open-angle glaucoma and 22 normal control subjects were subjected to a modified cold pressor test involving immersion of the right hand in 40 degrees C warm water followed by 4 degrees C cold water exposure, and finger and ocular blood flow were assessed by means of peripheral laser Doppler flowmetry and retinal flowmetry, respectively. Finger and body temperature as well as intraocular pressure, systemic blood pressure, systemic pulse pressure, heart rate, and ocular perfusion pressure were also monitored. RESULTS: The patients with glaucoma demonstrated an increase in diastolic blood pressure (P = 0.023), heart rate (P = 0.010), and mean ocular perfusion pressure (P = 0.039) during immersion of the tested hand in 40 degrees C water. During cold provocation, the patients demonstrated a significant decrease in finger (P = 0.0003) and ocular blood flow (the parameter velocity measured at the temporal neuroretinal rim area; P = 0.021). Normal subjects did not demonstrate any blood flow or finger temperature changes during immersion of the tested hand in 40 degrees C water (P > 0.05); however, they exhibited increases in systolic blood pressure (P = 0.034) and pulse pressure (P = 0.0009) and a decrease in finger blood flow (P = 0.0001) during cold provocation. In normal subjects, the ocular blood flow was unchanged during high- and low-temperature challenge. CONCLUSIONS: Cold provocation elicits a different blood pressure, and ocular blood flow response in patients with primary open-angle glaucoma compared with control subjects. These findings suggest a systemic autonomic failure and ocular vascular dysregulation in POAG patients.     

中国陕西省农村人群血压、眼压和原发性开角型青光眼流行病学调查

目的：调查中国陕西省农村≥50岁人群原发性开角型青光眼、眼内压与全身血压的联系。 方法：2003-07／12，采用整体随机分层抽样法在陕西省洋县、靖边县及富平县调查8500人，其中≥50岁人群2125人，所有受检人员均进行标准问卷调查及详细的眼科检查，包括视力检查、裂隙灯检查、测量眼压及散瞳后直接检眼镜检查眼底。受检者于坐位测量血压。若有可疑青光眼性视盘损害或眼压高于22mmHg者则应进行视野检查。 结果：≥50岁人群中有1775人完成了青光眼的相关检查，受检率为83．53％。通过相关分析，发现此人群中眼压与全身性血压有显著相关性；眼压与收缩压均随年龄的增长而显著升高。通过多因素logistic回归分析，显示原发性开角型青光眼与低舒张期灌注压有显著联系，但未发现原发性开角型青光眼与高血压的显著联系。 结论：中国陕西省农村≥50岁人群中原发性开角型青光眼的患病率与中国其他报道相近。证实较低的舒张期灌注压是原发性开角型青光眼的一个重要危险因素。     

Correlation between finger blood flow and changes in optic nerve head blood flow following therapeutic intraocular pressure reduction

PURPOSE: To correlate finger blood flow and changes in optic nerve head (ONH) blood flow following therapeutic intraocular pressure (IOP) reduction in open-angle glaucoma (OAG) and ocular hypertension (OHT). METHODS: Seventeen open-angle glaucoma patients and nineteen ocular hypertension patients underwent therapeutic IOP reduction followed by a minimum of 4 weeks of follow-up. Optic nerve head blood flow measurements were obtained by scanning laser Doppler flowmetry using full-field perfusion image analysis. Finger blood flow was measured using the Transonic laser Doppler Flowmeter. Finger blood flow was measured at baseline, after immersion in warm water (40 degrees C) for 2 minutes (Flow Max), and after immersion in cold water (4 degrees C) for 10 seconds (Flow Min). Patients were identified as vasospastic if their Flow Max/Flow Min >7. Statistical comparisons were performed using two-tailed distribution paired T-test and Pearson's correlation factor. RESULTS: For similar mean percentage intraocular pressure reduction, vasospastic patients had greater improvements in rim blood flow than did non-vasospastic patients [+35% versus +13%] (P = 0.01). While there was no difference in rim blood flow changes in the vasospastic versus the non-vasospastic OAG group, the vasospastic ocular hypertension group showed 18% increase in rim blood flow whereas the non-vasospastic ocular hypertension group showed an 8% decrease. A significant negative correlation was also found in the open-angle glaucoma group between rim blood flow change and Flow Max (-0.681, P = 0.003). In contrast, no such correlation was found in the ocular hypertension group (+0.144, P = 0.556). CONCLUSION: OAG patients had a significant negative correlation between changes in rim blood flow and maximum finger Doppler flow. Among ocular hypertension patients, increased rim blood flow was only found in the vasospastic group, though this increase was not statistically significant. These results suggest that open-angle glaucoma and ocular hypertension patients with the most severe vasospastic disease may show the greatest improvements in rim blood flow after sustained intraocular pressure reduction.     

The impact of ocular blood flow in glaucoma

Two principal theories for the pathogenesis of glaucomatous optic neuropathy (GON) have been described--a mechanical and a vascular theory. Both have been defended by various research groups over the past 150 years. According to the mechanical theory, increased intraocular pressure (IOP) causes stretching of the laminar beams and damage to retinal ganglion cell axons. The vascular theory of glaucoma considers GON as a consequence of insufficient blood supply due to either increased IOP or other risk factors reducing ocular blood flow (OBF). A number of conditions such as congenital glaucoma, angle-closure glaucoma or secondary glaucomas clearly show that increased IOP is sufficient to lead to GON. However, a number of observations such as the existence of normal-tension glaucoma cannot be satisfactorily explained by a pressure theory alone. Indeed, the vast majority of published studies dealing with blood flow report a reduced ocular perfusion in glaucoma patients compared with normal subjects. The fact that the reduction of OBF often precedes the damage and blood flow can also be reduced in other parts of the body of glaucoma patients, indicate that the hemodynamic alterations may at least partially be primary. The major cause of this reduction is not atherosclerosis, but rather a vascular dysregulation, leading to both low perfusion pressure and insufficient autoregulation. This in turn may lead to unstable ocular perfusion and thereby to ischemia and reperfusion damage. This review discusses the potential role of OBF in glaucoma and how a disturbance of OBF could increase the optic nerve's sensitivity to IOP.     

Comparison of ocular hypotensive effect and safety of brinzolamide and timolol added to latanoprost

PURPOSE: To compare the ocular hypotensive effect and safety of brinzolamide and timolol added to latanoprost monotherapy. METHODS: In prospective randomized fashion, we evaluated the ocular hypotensive effect and safety of brinzolamide or timolol in 1 eye of 32 patients with primary open-angle glaucoma, normal-tension glaucoma, or ocular hypertension who had been treated with latanoprost for more than 1 month. Intraocular pressure (IOP), blood pressure, and pulse were measured before and at 4, 8, and 12 weeks. Corneal endothelial cell density was measured at baseline and at 12 weeks. RESULTS: The IOP was 17.8+/-1.7 mm Hg (mean+/-SD) before the addition of brinzolamide (n=15) and 15.7+/-2.1 mm Hg at 12 weeks (P<0.01). In comparison, the IOP was 18.5+/-3.7 mm Hg before the addition of timolol (n=15) and 15.8+/-3.2 mm Hg at 12 weeks (P<0.01). Both brinzolamide and timolol significantly decreased IOP at 12 weeks, by a mean of 2.0 mm Hg and mean 2.7 mm Hg, respectively, and were more effective than latanoprost alone (P<0.01), but there were no significant differences between the drugs and no significant differences in corneal endothelial cell density and blood pressure before and after addition of either drug. At 12 weeks, pulse was decreased in patients receiving timolol (P<0.01). As systemic adverse events, there was one instance of malar flushing after brinzolamide addition and episodes of chest discomfort after timolol addition in 1 patient. Ocular adverse events were slight. CONCLUSIONS: Brinzolamide and timolol added to latanoprost have similar ocular hypotensive effects and safety in primary open-angle glaucoma, normal-tension glaucoma, or ocular hypertension.     

Status of blood supply to the eye in patients with primary open-angle glaucoma depending on the value of systemic arterial pressure and level of ophthalmic tone

Blood supply to the eye was studied in 756 patients aged 40-82 years (1339 eyes) with primary open-angle glaucoma, systemic arterial pressure (AP) 105-170 mm Hg, and various level of intraocular pressure (IOP). Control group consisted of 340 healthy subjects (680 eyes) aged 28-80 years without ophthalmic diseases with the same AP values. Blood supply values in the controls were taken for the norm. They were in high correlation with systemic AP. Ocular blood supply in patients with primary open-angle glaucoma depends on systemic AP and IOP, particularly perfusion pressure (Pperf) which decreases by 3.1 mm Hg in patients with systemic AP of 126-139 mm Hg and moderately (from normal to moderate) increased IOP. If IOP increases in the interval from moderate to high in patients with the same AP, Pperf drops by 12.5 mm Hg. Pperf values indicate deterioration of ocular blood supply in patients with primary open-angle glaucoma and different levels of IOP.     

The role of blood pressure in glaucoma

Although intraocular pressure (IOP) remains an important risk factor for glaucoma, it is clear that other factors can also influence disease development and progression. More recently, the role that blood pressure (BP) has in the genesis of glaucoma has attracted attention, as it represents a clinically modifiable risk factor and thus provides the potential for new treatment strategies beyond IOP reduction. The interplay between blood pressure and IOP determines the ocular perfusion pressure (OPP), which regulates blood flow to the optic nerve. If OPP is a more important determinant of ganglion cell injury than IOP, then hypotension should exacerbate the detrimental effects of IOP elevation, whereas hypertension should provide protection against IOP elevation. Epidemiological evidence provides some conflicting outcomes of the role of systemic hypertension in the development and progression of glaucoma. The most recent study showed that patients at both extremes of the blood pressure spectrum show an increased prevalence of glaucoma. Those with low blood pressure would have low OPP and thus reduced blood flow; however, that people with hypertension also show increased risk is more difficult to reconcile. This finding may reflect an inherent blood flow dysregulation secondary to chronic hypertension that would render retinal blood flow less able to resist changes in ocular perfusion pressure. Here we review both clinical and experimental studies that have attempted to clarify the relationships among blood pressure, OPP and blood flow autoregulation in the pathogenesis of glaucoma.     

原发性开角型青光眼进展的危险因素研究概况

原发性开角型青光眼(POAG)进展的危险因素包括全身性及眼部因素,眼部因素包括眼压及非眼压因素.在以往的多中心研究中,眼压对于由高眼压症发展为POAG及其在POAG进展中的作用已经明确,而目前降低眼压也是临床惟一有效地延缓、控制青光眼视神经损害进展的主要因素.制定目标眼压,进行降眼压治疗尤其是控制昼夜眼压波动对于阻止青光眼进展非常重要.非眼压危险因素包括高龄、中央角膜厚度增厚、视乳头出血、晶状体囊膜剥脱征、初始的青光眼严重程度及双眼罹患青光眼等.其他因素包括近视、青光眼家族史、眼部低灌注压、低血压、心血管疾病、高血压、高血脂等血管或血液性因素.POAG进展的危险因素研究在一定程度上揭示了POAG的发病机制及临床发病规律,对于指导临床医师决定随诊频率、选择治疗方案及提高治疗效率意义重大.     

Systemic blood pressure in glaucoma patients

Blood pressure was monitored for 24 h in 32 control patients, 38 open-angle glaucoma patients referred because of decompensated IOP despite maximum treatment, 40 patients with open-angle glaucoma referred because of progressive damage despite controlled IOP, and 39 normal-tension glaucoma patients. In the control group a physiological drop in blood pressure during the night was observed. The patients referred with uncontrolled IOP had blood pressure very similar to that of the control group during both day and night. However, the open-angle glaucoma patients with progression despite well-controlled IOP and also the patients with normal-tension glaucoma had markedly, and statistically significantly, lower systolic blood pressure during both day and night. The difference in diastolic blood pressure was smaller. Thus, blood pressure should be considered in diagnosis.     

Open-angle glaucoma associated with Graves disease

PURPOSE: To estimate the prevalence of open-angle glaucoma, including normal-tension glaucoma, in association with Graves disease. METHODS: In a prospective study, a complete ophthalmic examination including applanation tonometry, exophthalmometry, automated static threshold perimetry, and computed tomography of the orbit was performed in 104 consecutive Japanese patients with Graves disease (age range, 11 to 86 years; mean, 42 years; 80 women, 24 men). Ocular hypertension was defined as an intraocular pressure greater than 21 mm Hg on at least two occasions during the period of follow-up. RESULTS: Of the 104 patients, 14 (13%) exhibited typical glaucomatous visual field defects in automatic static threshold perimetry in the absence of compressive optic neuropathy. The intraocular pressure in seven of the 14 patients was consistently less than 21 mm Hg during the follow-up period. Thus, these patients were diagnosed as having normal-tension glaucoma. Of the 104 patients, 23 (22%) were diagnosed as having ocular hypertension. CONCLUSIONS: The prevalence of normal-tension glaucoma as well as open-angle glaucoma and ocular hypertension was significantly higher among patients with Graves disease than in the general population.     

Weather influences on intraocular pressure in patients with chronic glaucoma or ocular hypertension

From January 1979 to August 1984 intraocular pressure (IOP) was measured on the first Friday of each month under comparable conditions (same instruments, nearly always the same examiner) in a total of 109 patients in whom a primary chronic open-angle glaucoma or ocular hypertension had been diagnosed: The IOP was correlated to the local weather parameters (atmospheric pressure, cloud cover, relative air humidity, mean, maximum and minimum temperature, precipitation, duration of sunshine, mean and maximum wind velocity). In the large number of measurements a significant correlation was found only between IOP and atmospheric pressure: IOP was lower when air pressure was high. There was only a suggestion of a significant correlation between IOP and relative air humidity. However, further statistical analysis revealed that in fact both atmospheric pressure and relative air humidity account for only a negligible part of the variation in IOP values. From a practical point of view, therefore, the IOP of patients with primary chronic open-angle glaucoma or ocular hypertension is not influenced by weather conditions.     

Open-angle glaucoma clinical presentation and management]

Both primary open-angle and normal-tension glaucoma belong to an identical spectrum of diseases. Clinical presentations of primary open-angle or high-tension glaucoma (POAG) and normal-tension glaucoma (NTG) were studied in an attempt to determine prognostic, clinical factors and define the appropriate management. Clinical data obtained from 826 primary open-angle and normal-tension glaucoma patients were analyzed. In addition, the results of laboratory studies, including the immunological assay of heat shock protein (hsp) and gene analyses which were undertaken to identify risk factors at the molecular level, are discussed. 1. The identified prognostic factors were disk hemorrhage, peripapillary chorioretinal atrophy (PPA), maximum intraocular pressure (IOP), the recovery rate of skin temperature after exposure to cold, family history of glaucoma, systemic systolic channel blood pressure, and oral administration of Ca(2+)-channel antagonists. 2. Disk hemorrhage was observed in 30.5% of NTG patients and 15.4% of POAG patients. Cumulative probability of hemorrhagic events was 16.9% in POAG and 38.4% in NTG patients at the end of a 14.8-year follow-up. 3. The hazard ratio of disk hemorrhage decreased with the increase of IOP(26%/5 mmHg) and was 1.46 times higher in females than in males. Disk hemorrhage was closely associated with PPA: PPA becomes greater in association with the progression of glaucomatous optic neuropathy in both POAG and NTG. No such correlation was noted in primary angle-closure glaucoma. 4. Color Doppler imaging analyses and the hourly determination of ocular perfusion pressure (OPP) indicated a difference in retrobulbar hemodynamics between OPP-mean deviation concordant and OPP-mean deviation discordant patients: a circulatory disturbance causally unrelated to OPP seems to be involved in the OPP-mean deviation discordant patients. 5. The oral administration of Ca(2+)-channel antagonists was shown to favorably influence retrobulbar hemodynamics in NTG patients. 6. Serum antigen titer to hsps(hsp 27, alpha B crystallin, human & bacterial hsp 60) was higher in both POAG and NTG patients than in normal subjects. None of the hsp-antigens was correlated to any morphometric parameters of the optic disk or any global indices of the visual field. 7. Myocilin mutation was noted in only 0.5% of POAG patients and 2.37% of NTG patients. The very low rate of occurrence precludes the value of mutation of the gene as a prognostic factor in open-angle glaucoma(OAG). 8. IOP reduction achieved by mitomycin-C trabeculectomy is effective in maintaining visual function in OAG eyes. 9. Brovincamine fumarate is effective in inhibiting the progression of glaucomatous field loss in NTG.     

Relative risk factors in chronic open-angle glaucoma: an epidemiological study.

Some hypothesized risk factors in chronic open-angle glaucoma were investigated in a sample of 87 patinets with glaucoma and 87 matched controls. A significant positive association was found with diabetes, a systolic blood pressure/intraocular pressure (BP/IOP) ratio less than 5.75, and the taking of medication for systemic hypertension. No significant association was found with a history of smoking or an elevated systemic blood pressure. Analysis indicates that the systolic BP/IOP index may be useful as a screening test for the detection of glaucoma in samples where the prevalence of glaucoma is high.     

Oculo-oscillodynamography findings in glaucoma without hypertension

Oculo-oscillodynamography after Ulrich was performed in 27 patients suffering from glaucoma without hypertension (so-called low-tension glaucoma). Patients who had severe systemic disease or were receiving systemic medication which might influence IOP, and patients with narrow angle and an IOP higher than 22 mm Hg were excluded. In 85% of the patients a severe decrease in systolic ciliary perfusion pressure was found, whereas the systolic retinal and diastolic ocular perfusion pressures were significantly lower in almost 30% of the cases. Glaucoma without hypertension appears to be caused by the vascular change at the disk.     

The relationship between intraocular pressure and glaucoma in a defined population. Data from the Egna-Neumarkt Glaucoma Study

PURPOSE: To provide data on the prevalence of ocular hypertension and glaucoma and on the diagnostic validity of tonometry. METHODS: In this cross-sectional, population-based study, 4,927 subjects over 40 years of age were examined. Each subject underwent a complete ocular examination as part of the Egna-Neumarkt Glaucoma Study. These examinations were carried out by trained, quality-controlled ophthalmologists, according to a predetermined standard protocol that included a medical interview, applanation tonometry, computerized perimetry, optic nerve head examination and other ocular measurements. The following data were recorded: mean IOP, prevalence of ocular hypertension, primary open-angle glaucoma and normal tension glaucoma. Sensitivity, specificity and the predictive value of the tonometric test, as well as the distribution of IOP in the different groups were also determined. RESULTS: The overall prevalence of ocular hypertension, hypertensive primary open-angle glaucoma and normal tension glaucoma corresponded to 2.1, 1.4 and 0.6%, respectively. Other types of glaucoma accounted for a further 0.9%. The sensitivity and specificity of the tonometric test in recognizing glaucoma (cut-off between 21 and 22 mm Hg) were, respectively, 80.1 and 97.8%. The predictive values of the positivity and negativity of the test were 52.1 and 99.4%, respectively. CONCLUSIONS: The prevalence of ocular hypertension and glaucoma was similar to that found in several recent epidemiological studies. Tonometry alone is obviously not sufficient to ascertain or to exclude the presence of glaucoma; its diagnostic validity however is high and should never be underestimated. An elevated IOP is the main risk factor for glaucoma, with the degree of risk increasing as the level of IOP increases.     

The effects of latanoprost and brimonidine on blood flow velocity of the retrobulbar vessels: a 3-month clinical trial

OBJECTIVE: To investigate the effects of topical latanoprost 0.005% and topical brimonidine tartrate 0.2% on retrobulbar blood flow in patients with primary open-angle glaucoma (POAG) and ocular hypertension (OHT). METHODS: Forty-one consecutive patients with POAG and OHT were enrolled in this prospective, open-label, randomized, parallel study. Patients received either latanoprost 0.005% or brimonidine 0.2% for 3 months. Baseline retrobulbar blood flow measurements of the ophthalmic artery, central retinal artery and temporal short posterior ciliary artery were taken using colour Doppler imaging ultrasound, concurrently with systemic blood pressure, heart rate, ocular perfusion pressure and intraocular pressure (IOP) measurements. These measurements were repeated after 3 months. RESULTS: Both latanoprost and brimonidine significantly reduced IOP (p < 0.05). While there was a statistically significant increase in peak systolic velocity of the ophthalmic artery, no significant change was observed in the other vessels with latanoprost treatment (p < 0.05). Topical brimonidine did not significantly alter flow velocities or resistive indices in the retrobulbar vessels after 3 months. CONCLUSION: Topical latanoprost and brimonidine significantly reduced IOP in patients with POAG and OHT without causing significant haemodynamic alterations in the retrobulbar vessels.     

Efficacy and safety of latanoprost eye drops for glaucoma treatment: a 1-year study in Japan

PURPOSE: To evaluate the intraocular pressure (IOP)-lowering effect and safety of latanoprost, a prostaglandin analogue, in patients with primary open-angle glaucoma or ocular hypertension. METHOD: One hundred and twenty-four Japanese patients with primary open-angle glaucoma or ocular hypertension were enrolled in this open-labeled study and were treated with 0.005% latanoprost once daily for 1 year. RESULTS: At all follow-up visits there was a significant (P < .001) reduction in IOP compared with the baseline value. After 1 year, the IOP was reduced by 5.4 +/- 2.9 (mean +/- SD) mm Hg from a baseline value of 23.5 +/- 2.2 mm Hg. No evidence of an upward drift in the IOP was observed during the treatment period. The most frequently reported adverse ocular events were mild conjunctival hyperemia and iris pigmentation. Very few adverse systemic events were observed. CONCLUSIONS: Latanoprost eye drops showed a marked and stable IOP-lowering effect during the 1-year treatment period. Furthermore, latanoprost was well-tolerated and should be a valuable contribution to the management of glaucoma.     

Effects of caffeine on intraocular pressure: the Blue Mountains Eye Study

PURPOSE: To examine the relationship between coffee and caffeine intakes and intraocular pressure (IOP). MATERIALS AND METHODS: The Blue Mountains Eye Study examined 3654 participants aged 49+ years in an area west of Sydney, Australia. A detailed medical history questionnaire included average daily intakes of coffee and tea. The eye examination included Goldmann applanation tonometry and automated perimetry. Participants using glaucoma medications or who had previous cataract or glaucoma surgery or signs of pigmentary glaucoma/pigment dispersion, were excluded. Mean and maximum IOP calculations were used. RESULTS: Participants with open-angle glaucoma (OAG) who reported regular coffee drinking had significantly higher mean IOP (19.63 mm Hg) than participants who said that they did not drink coffee (16.84 mm Hg), after multivariate adjustment, P = 0.03. Participants consuming > or = 200 mg caffeine per day had higher mean IOP (19.47 mm Hg) than those consuming < 200 mg caffeine per day (17.11 mm Hg), after adjusting for age, sex, and systolic blood pressure (SBP), P = 0.06. This association did not reach statistical significance after multivariate adjustment. No association between coffee or caffeine consumption and higher IOP was found in participants with ocular hypertension (OH) and those without open-angle glaucoma. CONCLUSIONS: In participants with open-angle glaucoma, this study identified a positive cross-sectional association between coffee consumption/higher caffeine intakes and elevated intraocular pressure.