Large diurnal variation of intraocular pressure despite maximal medical treatment in juvenile open angle glaucoma

PURPOSE: To report the clinical significance of large fluctuations in intraocular pressure (IOP) and the effect of trabeculectomy on diurnal IOP variations in 2 cases of maximally medically treated juvenile open angle glaucoma (JOAG). PATIENTS AND METHODS: A 24-hour IOP monitoring was performed before and after trabeculectomy on both eyes of 2 JOAG patients-one with transiently blurred vision early in the morning, the other with progression of visual field defect despite apparently well-controlled IOP. The patients' optic discs were scanned with Heidelberg retina tomograph (HRT) during peak and trough IOPs before trabeculectomy. RESULTS: Preoperatively, diurnal IOP varied widely up to 20/19 (OD/OS) mm Hg in case 1 and up to 16/22 (OD/OS) mm Hg in case 2, even though both patients were using 4 different types of antiglaucoma eye drops. Peak IOP was associated with temporary blurring of vision and mild corneal edema in 1 patient (case 1). Heidelberg retina tomograph revealed a deepening of the optic cup and a resultant narrowing of the neuroretinal rim at peak IOP in this patient; this was not detected in the second patient who had tilted optic discs. After trabeculectomy, diurnal IOP fluctuations were reduced to 4-6/2-4 (OD/OS) mm Hg in case 1 and to 6-7/3-7 (OD/OS) mm Hg in case 2, with a decrease in peak IOPs as well. CONCLUSIONS: Wide diurnal variation should be suspected in JOAG patients, even when receiving maximal medical treatment; this is especially important in cases with temporary blurred vision and/or progression of visual field defect despite apparently well-controlled IOP. Trabeculectomy was more effective in reducing diurnal IOP variation than medical treatment.     

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.     

Five-year risk of progression of ocular hypertension to primary open angle glaucoma. A population-based study

PURPOSE: To report the progression of ocular hypertension (OHT) to primary open angle glaucoma (POAG) during a 5-year follow up of a population-based sample. METHODS: Twenty-nine patients diagnosed to have OHT and 110 randomly selected normals from a population-based study in 1995 were invited for ocular examination in 2000. All patients underwent a complete ophthalmic examination; including the daytime diurnal variation of intraocular pressure (IOP) and measurement of central corneal thickness (CCT). The "corrected" IOP was used for analysis. Progression to POAG was based on typical optic disc changes with corresponding field defects on automated perimetry. RESULTS: Twenty-five of the 29 persons with OHT who could be contacted were examined. After correcting for CCT, two persons were reclassified as normal. Four of 23 (17.4%; 95% CI: 1.95-32.75) had progressed to POAG. One person amongst the 110 normals progressed to normal tension glaucoma (NTG). The relative risk of progression amongst OHT was 19.1 (95% CI: 2.2-163.4). All those who progressed had bilateral OHT. The mean and peak IOP in those who progressed was 25.4 mm Hg and 29.3 mm Hg compared to 23.9 mm Hg and 25.7 mm Hg in those who did not. Those who progressed had more than 8 mm Hg diurnal variation. The diurnal variation was less than 6 mm Hg in those who did not progress. No patient developed blindness due to glaucoma. CONCLUSION: The 5-year incidence of POAG amongst OHT in this population was 17.4% (3.5% per year). Bilateral OHT, higher peak IOP and large diurnal variation may be the risk factors for progression.     

正常眼压性青光眼与原发性开角型青光眼24小时眼压曲线的比较

目的 通过24 h眼压的测量来深入分析比较正常眼压性青光眼(NTG)与原发性开角型青光眼(POAG)的眼压曲线特征.方法 前瞻性病例对照研究.收集2006年4月至2009年4月在上海市闸北区北站医院和复旦大学附属眼耳鼻喉科医院门诊就诊的NTG患者131例及POAG患者102例,测量24 h眼压,用非接触性眼压计从8 am起每隔2 h测一次眼压,0 am至6 am之间测得的为唤醒后即刻坐位眼压.主要观察指标为眼压波动曲线、平均眼压、峰值时间及眼压、谷值时间及眼压和眼压波动值.采用独立样本t检验和卡方检验比较各指标在两组之间的差异.结果 NTG组双眼平均眼压为(14.2±2.1)mmHg,低于POAG组[(19.9±3.5)mmHg];NTG组双眼峰值眼压为(17.0±2.4)mmHg,低于POAG组[(24.7±4.3)mmHg];NTG组双眼谷值眼压为(11.8±2.2)mmHg,低于POAG组[(16.5±3.1)mmHg];NTG组双眼眼压波动值为(5.2±1.8)mmHg低于POAG组(8.2±3.1)mmHg];两组的平均眼压、峰值、谷值及眼压波动值的差异均有统计学意义(t=-14.52、-16.44、-13.16、-8.90,P均＜0.01).NTG组63.3%患者、POAG组73.5%患者的峰值眼压位于门诊工作时间以外;尤其是NTG组有51.5%患者、POAG组有64.7%患者的峰值位于0 am至6 am时间段,两组差异有统计学意义(X2=8.150,P=0.017).结论 NTG及POAG患者24 h眼压曲线的变化规律具有相似性,是诊断和个体化治疗方案制订的依据,并可用作治疗随访中评价疗效和调整方案的重要参考指标.     

Sequential office pressure measurements in the management of glaucoma

PURPOSE: To evaluate the usefulness of day-long sequential office measurements of intraocular pressure (IOP) to make therapeutic decisions in patients with progressive glaucomatous damage despite apparently 'controlled' IOP. METHODS: We reviewed the records of 93 consecutive glaucoma patients (185 eyes) who underwent sequential office IOP measurements (every hour from 7 AM to 5 PM on a single day). These included 53 patients with normal-tension glaucoma (NTG), 12 glaucoma suspects (GS), and 28 patients with primary open-angle glaucoma (POAG) whose visual field deteriorated despite apparently 'controlled' IOP. Only one eye per patient was included in the study. RESULTS: The pattern of the day-long IOP curve was similar in the 3 groups of patients. IOPs were highest in the early morning hours in all groups. The mean +/- SD of the IOP range was 5 +/- 2 mm Hg. An IOP > 21 mm Hg was found in 3 eyes (3%), whereas a range of IOPs > 5 mm Hg was detected in 33 eyes (35%). In the NTG group, there was a significant correlation between visual field deterioration and the peak and range of IOP (P = 0.0002 and P = 0.05, respectively). CONCLUSIONS: Day-long sequential office IOP measurements are useful in selected patients who demonstrate progressive glaucomatous damage. Early morning measurements are most frequently highest. The range of IOP may be as important, or more important than, the peak IOP level.     

Effect of latanoprost on diurnal variations of intraocular pressure in normal-tension glaucoma

OBJECTIVES: To study the effect of instillation of latanoprost on the diurnal variation in the intraocular pressure(IOP), blood pressure, and pulse rate in patients with normal-tension glaucoma(NTG). SUBJECTS AND METHODS: The diurnal variation in the IOP was determined in 23 eyes in 23 NTG patients after a washout period of 4 weeks or longer. The diurnal variation in IOP was then remeasured after latanoprost monotherapy of 8 weeks or longer. The IOP was measured by the Goldmann applanation tonometer at 10:00, 13:00, 16:00, 19:00, 22:00, 01:00, 03:00, 07:00, and 10:00 before and after treatment, and the IOP at each time point, mean diurnal IOP, maximum IOP, minimum IOP, and range of variation in IOP were compared before and after treatment. The blood pressure and pulse rate before and after treatment were also measured and compared. RESULTS: The IOP decreased significantly at all time points. The treatment caused significant decreases in the mean diurnal IOP, maximum IOP, minimum IOP, and range of variation in IOP. There were no differences in the blood pressure and pulse rate before and after treatment. CONCLUSIONS: Latanoprost significantly decreases the IOP throughout the day in NTG patients, and has no effects on the blood pressure and pulse rate. It is therefore useful in the treatment of NTG.     

正常眼压性青光眼与高眼压性青光眼视神经图像分析的对比研究

目的 探讨正常眼压性青光眼 (normal-tension glaucoma, NTG)与高眼压性青光眼(high-tension glaucoma, HTG)视盘和视神经纤维层(retinal nerve fiber layer, RNFL)损害的差异。 方法 选择具有青光眼性视神经损害或RNFL缺损、相应的视野缺损的青光眼患者,NTG至少2次24 h眼压曲线和多次眼压测量均≤21 mm Hg(1 mm Hg =0.133 kPa)，HTG的眼压至少2次测量≥25 mm Hg。患者进行详细的眼科检查，同时用扫描激光偏振仪(scanning laser polarimetry, SLP)、光学相干断层扫描（optical coherence tomography, OCT）和海德堡视网膜成像仪(Heidelberg retinal tomography, HRT)定量测定视盘形态和RNFL厚度。比较两组视盘总体和相同象限测量参数。 结果 30例 NTG和 19例 HTG (共49只眼)患者的平均年龄分别为(59.6±8.6)岁(39～71岁)和(59.2±12.3)岁(36～75岁)。两组间视野缺损的平均偏差(mean deviation, MD)差异不显著(P＞0.05)。HRT测量的视盘 C/D面积比，除鼻侧象限外,NTG者视盘总体和上、下、颞侧3个象限均显著大于HTG者(P＜0.05 ),而盘缘面积小于HTG者(P＜0.05)；两组间其他视盘参数差异不显著。3种激光扫描技术所测定的总体和象限RNFL厚度，两组间差异不显著。 结论 NTG趋向大 C/D面积比和窄盘缘面积。RNFL缺损的形态分布须更精细和节段性分析。 (中华眼底病杂志, 2002, 18: 109-112)     

Effect of hospitalization on intraocular pressure in patients with normal-tension glaucoma

OBJECTIVE: To investigate the effect of hospitalization on intraocular pressure (IOP) in patients with normal-tension glaucoma (NTG). METHODS: The study was conducted in 52 patients with a definite diagnosis of NTG. The correlation between IOP measured from 9.00 a.m. to 12.00 p.m. on an outpatient basis within 3 months each prior to and after hospitalization (ambulatory IOP) and IOP measured during the same time period after admission (inpatient IOP) was investigated in NTG patients. RESULTS: Inpatient IOP (13.9 +/- 2.4 mm Hg) was significantly lower than ambulatory IOP (15.2 +/- 2.1 mm Hg), with a difference of 1.3 +/- 2.0 mm Hg (p < 0.01). The difference between inpatient IOP and ambulatory IOP was negatively correlated with inpatient IOP (r = 0.58, p < 0.01). CONCLUSIONS: These results revealed that hospitalization decreased IOP in NTG patients, with the decrease being particularly pronounced in cases of low ambulatory IOP. Interpretation of inpatient IOP should be carefully included in glaucoma treatment.     

Impact of intraocular pressure fluctuations on progression of normal tension glaucoma

AIM: To investigate short- and long-term intraocular pressure (IOP) fluctuations and further ocular and demographic parameters as predictors for normal tension glaucoma (NTG) progression. METHODS: This retrospective, longitudinal cohort study included 137 eyes of 75 patients with NTG, defined by glaucomatous optic disc or visual field defect with normal IOP (<21 mm Hg), independently from therapy regimen. IOP fluctuation, mean, and maximum were inspected with a mean follow-up of 38mo [standard deviation (SD) 18mo]. Inclusion criteria were the performance of minimum two 48-hour profiles including perimetry, Heidelberg retina tomograph (HRT) imaging, and optic disc photographs. The impact of IOP parameters, myopia, sex, cup-to-disc-ratio, and visual field results on progression of NTG were analyzed using Cox regression models. A sub-group analysis with results from optical coherence tomography (OCT) was performed. RESULTS: IOP fluctuations, average, and maximum were not risk factors for progression in NTG patients, although maximum IOP at the initial IOP profile was higher in eyes with progression than in eyes without progression (P=0.054). The 46/137 (33.5%) eyes progressed over the follow-up period. Overall progression (at least three progression confirmations) occurred in 28/137 eyes (20.4%). Most progressions were detected by perimetry (36/46). Long-term IOP mean over all pressure profiles was 12.8 mm Hg (SD 1.3 mm Hg); IOP fluctuation was 1.4 mm Hg (SD 0.8 mm Hg). The progression-free five-year rate was 58.2% (SD 6.5%). CONCLUSION: Short- and long-term IOP fluctuations do not result in progression of NTG. As functional changes are most likely to happen, NTG should be monitored with visual field testing more often than with other devices.     

Intraocular pressure asymmetry and undiagnosed open-angle glaucoma in an older population

PURPOSE: To quantify prevalence of asymmetric intraocular pressure (IOP) and assess associations with undiagnosed open-angle glaucoma. DESIGN: Population-based cross-sectional study. METHODS: Participants underwent applanation tonometry. Intraocular pressure asymmetry was defined for differences > or = 3 mm Hg; open-angle glaucoma was diagnosed if glaucomatous optic disk and field changes were congruous. Analyses excluded subjects using glaucoma medication, known glaucoma, pseudoexfoliation, and cataract surgery. RESULTS: Intraocular pressure asymmetry was present in 5.1% of subjects and was greater for patients older than 70 years (6.2%). Of subjects with maximum IOP > 21 mm Hg, IOP asymmetry was present in 41.1%. Undiagnosed open-angle glaucoma was more frequent among subjects with (4.8%) than without (1.2%) IOP asymmetry. This relationship remained significant for maximum IOP < or = 21 mm Hg. CONCLUSIONS: Intraocular pressure asymmetry may be a useful sign of undiagnosed glaucoma in subjects without elevated IOP.     

Three and five year changes in intraocular pressures after clear corneal phacoemulsification in open angle glaucoma patients, glaucoma suspects, and normal patients

PURPOSE: This study evaluates the change in intraocular pressure (IOP) and glaucoma medication requirements after clear corneal phacoemulsification in open angle glaucoma patients, glaucoma suspects, and normal patients at 3 years and last follow-up (mean 5 y). PATIENTS AND METHODS: This study represents a retrospective analysis of patients who had clear corneal phacoemulsification and at least 3 years of follow-up. The patients were classified into 3 groups: glaucoma (G), glaucoma suspects (GS), and no glaucoma (NG). No patient had a history of previous intraocular surgery. Single factor analysis of variance, Fisher exact tests, 2-tailed paired Student t tests and Kaplan-Meier analysis were applied. RESULTS: Forty-eight patients (55 eyes) in the glaucoma group, 41 patients (44 eyes) in the GS group, and 59 patients (59 eyes) in the NG group met the above criteria. At 3 years follow-up IOP was significantly decreased in all groups; (G) group decreased 1.4+/-3.3 mm Hg (P = 0.0025), GS 1.4+/-4.2 mm Hg (P = 0.004), and NG 1.7+/-3.1 mm Hg (P = 0.0005). At the final follow-up visit (mean near 5 y for all groups) the IOP was significantly decreased in all groups, (G) group 1.8+/-3.5 mm Hg (P = 0.005), GS 1.3+/-3.7 mm Hg (P = 0.025), and NG 1.5+/-2.5 mm Hg (P < 0.0001). The number of preoperative and postoperative glaucoma medications in the (G) group did not show any significant change at 3 and 5 years (P = 0.36, P = 0.87). Kaplan-Meier analysis shows that at 3 years, 85% of the (G) group, 81% of GS, and 90% of the NG had IOPs less than or equal to their preoperative IOP, with the same number of glaucoma medications or less. At 5 years the percentages were 76%, 79%, and 85%, respectively. CONCLUSIONS: This study demonstrates that cataract removal by clear cornea phacoemulsification in glaucoma patients, glaucoma suspects, and normal patients results in a small but significant decrease in IOP that is sustained at 3 years and a mean of 5 years in all groups. This study does not imply that cataract removal by phacoemulsification is a substitute for a combined procedure but may be an appropriate procedure for certain patients based on medication requirements and extent of optic nerve damage.     

Clinical features and course of patients with glaucoma with the E50K mutation in the optineurin gene

PURPOSE: To investigate the clinical features of subjects with glaucoma with the E50K mutation in the optineurin (OPTN) gene and to compare the onset, severity, and clinical course of these patients with a control group of subjects with glaucoma without this mutation. METHODS: The phenotype of well-characterized subjects from Moorfields Eye Hospital, London, who had been identified as carrying the OPTN E50K mutation was examined. A wide range of structural, psychophysical, and demographic factors were then compared with those in a control group of subjects with glaucoma without this mutation. RESULTS: Eleven subjects with glaucoma with the E50K mutation (nine in two families and two sporadic cases) were studied. All 11 subjects had normal tension glaucoma (NTG), with presenting and highest IOP of 15.3 +/- 3.0 and 16.5 +/- 2.5 mm Hg (+/-SD) on diurnal testing. Compared with 87 NTG control subjects who did not have this mutation, subjects with E50K presented at a younger age (40.8 +/- 15 years, P = 0.0001) and had more advanced optic disc cupping (mean cup-disc ratio +/- SD 0.86 +/- 0.1, P = 0.001) and smaller neuroretinal rim area (+/-SD; 0.5 +/- 0.28 mm2, P = 0.001) at diagnosis. The rate of filtration surgery performed for progressive visual field loss in those with and without the E50K mutation was 72.7% and 25.3%, respectively (P = 0.003), and all subjects with E50K were found to have progressing visual fields. In addition, seven E50K mutation-carrying individuals in two families (age range, 23-58 years) presented with normal optic discs and visual fields and, as yet, no signs of glaucoma. CONCLUSIONS: In this study, subjects with glaucoma who had the OPTN E50K mutation were found to have NTG that appeared to be more severe than that in a control group of subjects with NTG without this mutation. The findings emphasize the importance of early detection and treatment of glaucoma in such individuals, to minimize visual loss.     

Primary open angle glaucoma in cornea plana masked by false normal applanation tonometry (Goldman) - a case report

BACKGROUND: Cornea plana is a rare syndrome, which leads to a flat corneal curvature due to a reduced sclero-corneal angle. Depending on the regularity of the corneal astigmatism the frequently resulting hyperopia may be difficult to compensate for. Because of the flatness of the cornea the anterior chamber is also flat, the anterior chamber angle can be restricted, and the applanatory intraocular pressures (IOPs) are measured too low. A primary open angle glaucoma is therefore not diagnosed for a long time, until changes of the optic nerve head occur.Patient and methods We report on a 66-year-old male with cornea plana. Although his intraocular pressure (IOP), measured with an applanation tonometer (Goldmann), had always been normal (< 21 mm Hg), he suffered from an increasing glaucomatous atrophy of the optic disc. We carried out a complete ophthalmological investigation, including keratometry and corneal topography analysis (TMS-1, Tomey). Furthermore, visual field was determined (G1, Octopus) and the optic nerve heads were documented and analysed by papillometry. A 48-hour tension profile was worked out for both eyes including applanation and Schi?tz tonometry.Results The central refractive power of the cornea was 31 diopters and the cornea seemed to be flattened on slit lamp evaluation. The glaucomatous atrophy of the optic disc was more pronounced in the OD than in the OS (OD=neuroretinal rim loss in the upper part, at the bottom and in the lateral part of the optic disc, OS=laterally distinct neuroretinal rim loss). While the anterior parts of the eye were shortened (depth of the anterior chamber was OD/OS=1.9 mm), a macrophthalmus posterior was stated (axial length OD=25.78 mm, OS=25.72 mm). However, the IOPs were measured below 21 mm Hg by applanation during the entire tension analysis, comparable values measured with the Schi?tz tonometer showed values above 21 mm Hg. We converted the applanatory IOP values according to the flat corneal power, as described in literature (addition of 1 mm Hg to the applanatory values per 3 diopters decreased corneal power). The tension analysis now showed increased values, as expected after observation of the glaucomatous excavated optic nerve head.Conclusion In patients with cornea plana applanatory IOPs are measured too low. Therefore in case of very flat corneas a mathematical correction of the applanatory IOP should be carried out, in order to diagnose a primary open angle glaucoma early enough.     

Novel pressure-to-cornea index in glaucoma

BACKGROUND: Several conversion tables and formulas have been suggested to correct applanation intraocular pressure (IOP) for central corneal thickness (CCT). CCT is also thought to represent an independent glaucoma risk factor. In an attempt to integrate IOP and CCT into a unified risk factor and avoid uncertain correction for tonometric inaccuracy, a new pressure-to-cornea index (PCI) is proposed. METHODS: PCI (IOP/CCT(3)) was defined as the ratio between untreated IOP and CCT(3) in mm (ultrasound pachymetry). PCI distribution in 220 normal controls, 53 patients with normal-tension glaucoma (NTG), 76 with ocular hypertension (OHT), and 89 with primary open-angle glaucoma (POAG) was investigated. PCI's ability to discriminate between glaucoma (NTG+POAG) and non-glaucoma (controls+OHT) was compared with that of three published formulae for correcting IOP for CCT. Receiver operating characteristic (ROC) curves were built. RESULTS: Mean PCI values were: Controls 92.0 (SD 24.8), NTG 129.1 (SD 25.8), OHT 134.0 (SD 26.5), POAG 173.6 (SD 40.9). To minimise IOP bias, eyes within the same 2 mm Hg range between 16 and 29 mm Hg (16-17, 18-19, etc) were separately compared: control and NTG eyes as well as OHT and POAG eyes differed significantly. PCI demonstrated a larger area under the ROC curve (AUC) and significantly higher sensitivity at fixed 80% and 90% specificities compared with each of the correction formulas; optimum PCI cut-off value 133.8. CONCLUSIONS: A PCI range of 120-140 is proposed as the upper limit of "normality", 120 being the cut-off value for eyes with untreated pressures or=22 mm Hg. PCI may reflect individual susceptibility to a given IOP level, and thus represent a glaucoma risk factor. Longitudinal studies are needed to prove its prognostic value.     

Autonomic system activity and 24-hour blood pressure variations in subjects with normal- and high-tension glaucoma

PURPOSE: As suggested by findings of abnormal responses to posture in patients with normal-tension glaucoma (NTG), cardiovascular autoregulation may also be defective in primary open-angle glaucoma (POAG). PATIENTS AND METHODS: Both 24-hour ambulatory blood pressure monitoring and the head-up tilt test were performed in 17 subjects with NTG and in 13 subjects with high-tension POAG (ht-POAG). These groups were compared with 17 age-matched healthy individuals. Subjects undergoing cardiovascular therapy were excluded. RESULTS: No significant differences in diurnal and nocturnal blood pressure and heart rate were found between the groups. A significant reduction in diurnal heart rate variability was found in NTG (12.1 +/- 2.8 bpm) compared with the ht-POAG (15.0 +/- 2.4 bpm, P < 0.01) and control groups (15.8 +/- 3.0 bpm, P = 0.01]). Nocturnal diastolic blood pressure variability was also reduced in NTG (6.9 +/- 2.2 mm Hg) compared with controls (8.6 +/- 2.3 mm Hg, P < 0.05]) as was heart rate variability (6.3 +/- 1.4 vs 8.3 +/- 2.6 in ht-POAG, P < 0.05), suggesting blunted blood pressure and heart rate modulation in NTG subjects. Spectral analysis of short-term heart rate variability showed a significant reduction of total power in the supine position (1064 +/- 600 in NTG vs 1688 +/- 889 ms2 in controls, P < 0.05]). This was not accompanied either by a physiological reduction in total power or in a high-frequency component during the passive orthostatic stimulus. These differences tend to become more prominent in the clinically more severe forms of NTG (as identified by scores based on the extent of optic disk excavation, visual field damage, and progression of disease). This would suggest a correlation between the extent of autonomic disorder and severity of glaucoma. The alpha index (root-square of low-frequency heart rate to low-frequency blood pressure ratio) was lower in the supine position in NTG subjects (8.1 +/- 3.1 vs 10.6 +/- 3.3 ms/mm Hg in controls, P < 0.05), confirming the reduced baroreflex sensitivity. CONCLUSIONS: The results confirm the hypothesis that dysfunction of autonomic control of the cardiovascular response may be a contributing pathogenetic factor in NTG, inducing a chronic ischemia of the optic nerve.     

Diurnal variation of intraocular pressure in suspected glaucoma patients and their outcome

Background A case-controlled prospective study was conducted to evaluate the diurnal variation of intraocular pressure (IOP); the mean, the amplitude of variation and the peak and trough times of pressure readings in the suspected open-angle glaucoma patients as compared with a control group. We also looked at the outcome of these suspects after diurnal variation of IOP measurements. Methods Diurnal variation of intraocular pressure was measured in 202 eyes of suspected open-angle glaucoma patients and 100 control eyes, at 4-hourly intervals for 24 hours (phasing). Based on the phasing results, optic disc changes and visual field defects, the patients were diagnosed as primary open angle glaucoma (POAG), normal tension glaucoma (NTG), ocular hypertension (OHT), or physiologic cup (PC), or still remained as glaucoma suspects due to inconclusive diagnosis. The last group (glaucoma suspects) was then followed up 6-monthly for their eventual outcome. Results The highest percentage of suspected glaucoma patients had peak (maximum) readings in the mid-morning (10–11 a.m.) and trough (minimum) readings after midnight (2–3 a.m.); the highest percentage of control group had peak readings in the late evening (6–7 p.m.) and trough readings after midnight (2–3 a.m.). The mean amplitude of variance was 6 mm Hg in suspected glaucoma group and 4 mm Hg in the control group. After ‘phasing’, 18.8% of the suspected glaucoma patients were diagnosed as POAG, 16.8% as NTG, 5% as OHT, and 28.7% as physiologic cup; 30.9% remained as glaucoma suspects. After 4 years follow-up, 70% of the glaucoma suspects still remained as glaucoma suspects, 6.7% developed NTG and another 6.7% POAG; 16.6% were normal. Conclusions Serial measurement of IOP ( phasing) in a 24-hour period is still needed, in order not to miss the peak and the trough IOP readings in suspected open-angle glaucoma patients, which helps in better management of glaucoma. Among 30.9% of patients who remained as glaucoma suspects after the initial phasing, 13.4% developed NTG/POAG over a period of 4 years. This paper was presented in part at the 19th Congress of Asia Pacific Academy of Ophthalmology (APAO), Bangkok, Thailand, 28 November-3 December 2003. The authors have no financial support in the writing of this paper.     

Central corneal thickness in low-tension glaucoma

BACKGROUND: It is possible that the intraocular pressure (IOP) is underestimated in eyes whose central cornea is thinner than normal. The objective of this study was to determine and establish the significance of central corneal thickness in patients with low-tension (normal-tension) glaucoma compared with those with chronic open-angle glaucoma (COAG) or ocular hypertension and healthy eyes. METHODS: The study was carried out from February 1998 to May 1999. Central corneal thickness was measured by ultrasonic pachymetry and IOP was measured by Goldmann applanation tonometry in 25 patients with low-tension glaucoma (untreated IOP less than 21 mm Hg with evidence of optic nerve head damage and corresponding visual field loss on automated perimetry), 80 patients with COAG (untreated IOP 21 mm Hg or greater with evidence of optic nerve head damage and corresponding visual field loss on automated perimetry), 16 patients with ocular hypertension (untreated IOP 21 mm Hg or greater, with normal optic nerve head and no history of glaucoma or elevated IOP, and normal visual field on automated perimetry) and 50 control subjects (untreated IOP less than 21 mm Hg with normal optic nerve head and no history of glaucoma or elevated IOP). Analysis with Pearson's product-moment correlation was performed to determine the correlation of IOP and central corneal thickness, and one-way analysis of variance was used to compare corneal thickness between groups. RESULTS: The central cornea was significantly thinner in the low-tension glaucoma group (mean 513.2 mu [standard deviation (SD) 26.1 mu]) than in the COAG group (mean 548.2 mu [SD 35.0 mu]) and the control group (mean 556.7 mu [SD 35.9 mu]) (p < 0.001). No significant difference in corneal thickness was found between the COAG and control groups. The ocular hypertension group had significantly thicker corneas (mean 597.5 mu [SD 23.6 mu]) than the three other groups (p < 0.001). INTERPRETATION: Patients with low-tension glaucoma may have thinner corneas than patients with COAG and healthy subjects. This results in underestimation of their IOP. Corneal thickness should be taken into account when managing these patients to avoid undertreatment.     

Lack of association between interleukin-1 gene cluster polymorphisms and glaucoma in Chinese subjects

PURPOSE: A recent study identified single nucleotide polymorphisms (SNPs) within the IL-1 gene cluster at chromosomal locus 2q13 that were associated with reduced risk for primary open-angle glaucoma (POAG) in whites. The purpose of this study was to investigate the association between IL-1 SNPs and glaucoma in Chinese patients with either POAG or primary-angle closure glaucoma (PACG). METHODS: Patients with POAG with a mean IOP without treatment that was consistently <21 mm Hg on diurnal testing were classified as having normal-tension glaucoma (NTG) and those with higher IOP were classified as having high-tension glaucoma (HTG). Subjects with PACG had at least 180 degrees of angle closure on gonioscopy. Genotypes were determined by polymerase chain reaction and restriction digest enzymes at the following loci: IL1A (-889C/T), IL1B (+3953C/T), and IL1B (-511C/T). The association of individual SNPs with glaucoma was evaluated by using chi(2) testing. Haplotype analysis was performed with the PHASE program, with haplotype frequency estimated for combined cases and controls, assuming Hardy-Weinberg equilibrium (HWE) of haplotypes. RESULTS: Of the Chinese subjects studies, 194 had POAG (94 NTG and 100 HTG), 125 had PACG, and 79 were normal control subjects. There was no significant difference in IL-1 SNP or allele frequencies for in subjects with POAG or PACG compared with control subjects, or between NTG and HTG. None of the common haplotypes showed any significant difference between the HTG, NTG, PACG, and normal control subjects. CONCLUSIONS: This study did not find an association between IL-1 gene cluster polymorphisms and glaucoma in this sample of Chinese subjects.     

Episcleral venous pressure in untreated primary open-angle and normal-tension glaucoma

The aim of this prospective study was to investigate episcleral venous pressure (EVP) in different forms of glaucoma in comparison with age-matched controls. EVP was measured by means of a venomanometer in 32 eyes with untreated primary open-angle glaucoma (POAG), 36 eyes with untreated normal-tension glaucoma (NTG) as well as 56 control eyes without ophthalmological disease other than cataract. In addition to ophthalmological standard examination, cardiovascular parameters such as systolic and diastolic blood pressure and heart rate were recorded. In the POAG group, EVP was 12.1 +/-0.5 mm Hg and in the NTG group 11.6 +/- 0.4 mm Hg. This was significantly different from EVP of the controls (9.5 +/- 0.2 mm Hg). The EVP/intraocular pressure (IOP) ratio was significantly different in NTG patients (80.0% +/- 3.2) in comparison with both POAG patients (67.1% +/- 2.8) and controls (69.2% +/- 2.4). The difference between IOP and EVP (IOP - EVP) was 6.2 +/- 0.6 in the POAG, 3.1 +/- 0.45 in the NTG and 4.5 +/- 0.4 in the control group. All these values were significantly different from each other. Regression analysis revealed a significant linear correlation between EVP and IOP in both the NTG and the POAG group. In the control group, however, the correlation was weak. This study is the first to demonstrate differences in EVP between untreated NTG and POAG and an age-matched healthy control group.     

Comparison of the intraocular pressure lowering effect of latanoprost and carteolol-pilocarpine combination in newly diagnosed glaucoma

PURPOSE: To evaluate the comparative efficacy of latanoprost monotherapy versus combined carteolol and pilocarpine therapy in patients with newly diagnosed glaucoma. METHODS: Masked randomized prospective trial. This study included 51 patients (64 eyes) with newly diagnosed glaucoma or ocular hypertension. The cases were randomly divided into two treatment groups for administration of latanoprost 0.005% once daily, or of carteolol 2% twice daily and pilocarpine 2% twice daily. Mean diurnal intraocular pressure (IOP) was measured at baseline, week 2, week 4, and month 3 after the beginning of treatment. Changes in mean IOP from baseline to the 3-month visit were determined by an analysis of variance. RESULTS: Mean diurnal IOP values were 25.1 +/- 3.1 mm Hg and 25.5 +/- 2.5 mm Hg at baseline in the latanoprost monotherapy group and in the carteolol-plus-pilocarpine group, respectively. Diurnal IOP was significantly decreased from baseline to 3 months in both groups (P <.001). At this time point, latanoprost monotherapy had reduced mean diurnal IOP by 7.2 +/- 2.5 mm Hg (28.7%) and carteolol plus pilocarpine had reduced mean diurnal IOP by 7.4 +/- 2.7 mm Hg (29%). There was no difference between the groups in terms of their IOP reduction effect (P =.51). Decreased visual acuity and twilight vision, blurred vision, and headache were more frequent in the carteolol-plus-pilocarpine group than in the latanoprost group (P <.05). CONCLUSIONS: We concluded that latanoprost monotherapy was at least as effective as the carteolol-pilocarpine combination therapy in reducing mean diurnal IOP in newly diagnosed glaucoma or ocular hypertension.