Primary open-angle glaucoma (POAG) and myopia are common ocular conditions among the global population.1–3 Epidemiologic evidence has confirmed a remarkable relationship between POAG and myopia, especially high myopia.3–5 High myopia and increased axial length have been considered as risk factors for developing POAG.6 Recently, many studies focused on the faster rate of glaucomatous progression of POAG combined with high myopia (POAG-HM).4,5 However, the reason for this has not yet been identified.
Other risk factors such as, intraocular pressure (IOP) and IOP fluctuation are most closely associated with glaucomatous progression. High IOP remains an undeniable risk factor.7,8–10 Results from the Early Manifest Glaucoma Trial (EMGT) showed that each 1 mmHg higher mean IOP was associated with an 11% increase in the risk of glaucomatous progression.11 However, there is controversy that whether IOP fluctuations, that is, short-term IOP (or 24-hour) fluctuation and long-term (or intervisit) IOP fluctuation, are independent risk factors for glaucomatous progression.7,12,13 Short-term IOP (or 24-hour) fluctuation refers to the change of IOP occurring only during a 24-hour period, which is calculated as peak IOP minus trough IOP. Asrani et al14 reported that 24-hour IOP fluctuation was a significant risk factor for glaucomatous progression whereas Liu et al15 showed negative outcomes. Long-term (or intervisit) IOP fluctuation refers to the change of IOP obtained during different visits over the follow-up period, which is calculated as the standard deviation (SD) of IOP measurements. Medeiros et al16 and EMGT8 reported that long-term IOP fluctuations were not associated with glaucomatous progression, while others showed each 1 mmHg higher long-term IOP fluctuation was associated with 31% higher risk of glaucomatous visual field loss progression.17,18 As IOP and IOP fluctuation are known risk factors for glaucoma, it is important to understand the effects of high myopia on these ocular parameters.
The focus of this study was to only investigate if POAG patients on only pharmacological glaucoma therapy who also have high myopia exhibit higher IOP and greater IOP fluctuations at resting conditions over 24 hours.
Consecutive Chinese patients, between 18 and 70 years of age, with POAG were screened from November 2010 to March 2011 at the Glaucoma Outpatient Department of Beijing Tongren Hospital in Beijing, China. All patients had a baseline IOP ≥21 mmHg, open angles (performing gonioscopy), glaucomatous change in the appearance of the optic disc on baseline stereophotographs (focal or diffuse thinning of the neuro-retinal rim, increased excavation, or appearance of retinal nerve fiber layer defects); and/or 3 consecutive abnormal but reliable visual field (VF) test results (a glaucoma hemifield test result outside normal limits and/or pattern SD with P <0.05). Reliable VF was defined as 33% or fewer of false-positive results, false-negative results, and fixation losses. All eligible patients included in the study were definitely diagnosed with POAG and locally used prostaglandin analogue alone at 10 pm. Exclusion criteria included: (1) previously treated with anti-glaucoma surgeries, and (2) presence of comorbid cardio-cerebral diseases. All patients signed informed consents to participate in the study and the entire study was reviewed and approved by the local Ethics Committee of Beijing Tongren Hospital. All experimental procedures were regulated to adhere to the Declaration of Helsinki of the World Medical Association. The trial was registered in the Chinese Clinical Trial Registry, and the trial registration number was ChiCTR-TRC-10001055 (registration site: http://www.chictr.org).
Eighty-two eligible patients with POAG were divided into 3 groups according to various myopic grades, namely, group POAG-HM (n=27): POAG combined with high myopia (-6 diopters (D) or less), group POAG-NHM (n=33): POAG combined non-high myopia (-0.76 to -5.99 D), group POAG-NM (n=22): POAG combined with non-myopia (emmetropia, -0.75 to 0.75 D). Refractive status was measured via a manifest refraction test using a spherical equivalent.
All study subjects were hospitalized, and asked not to perform any physical activity upon waking up. Before the start of the test, all subjects were asked to maintain a supine position for 15 minutes. The IOP measurements were taken from 8 am to minimize the effect of diurnal variation. The subjects were subjected to IOP recordings at 8 am, 10 am, 2 pm, 6 pm, 10 pm, 2 am and 6 am. These were considered the IOP measurements over 24 hours at resting conditions. In between the measurements, the study subjects rested in their respective beds in the hospital. The IOPs were measured using a non-contact pneumatonometer (NCT, Cannon HY9-RK-F1 Japan, automatic mode) in the sitting position. In each phase of the protocol, the IOP was measured in the right eye throughout by the same technician who was in another room and masked to study details. Every IOP measurement was performed automatically at least 3 times and, in the case a reading was unavailable on the display screen, a fourth measurement was performed, finally taking into account the mean of the 3 reliable values. Single time IOP at 10 am was measured using both Goldmann applanation tonometer (GAT) and NCT to correct IOP. Corrected IOP values in this paper=IOPNCT+ (IOPGAT-IOPNCT at 10 am). Single time IOP at 10 am refers to the IOP value measured by GAT. Mean corrected 24-hour IOP refers to the mean IOP after corrected at the seven time points. Mean corrected night IOP refers to the mean IOP at the time points of 6 pm, 10 pm, and 2 am. The 24-hour IOP fluctuation refers to the value of peak IOP minus trough IOP in 24 hours.
Goldmann applanation tonometry attached to the slitlamp (Hagg-Streit, Switzerland)) was used to measure IOP at 10 am in the right eye. Before each measurement, one drop of a combination of benoxinate hydrochloride (0.4%) and fluorescein sodium (0.25%) was instilled in the eye. Each IOP measurement was performed at least twice and, in the case of more than a 2 mmHg difference, a third measurement was performed, finally taking into account the mean of the two highest values.
All data were described by mean and SD if the continuous data were normally distributed. Analysis of variance (ANOVA) were used to analyze single time IOP at 10 am, mean corrected diurnal IOP, mean corrected night IOP and 24-hour IOP fluctuation. Repeated measurement analysis of variance was used to analyze 24-hour corrected IOP. A chi-square test was used to analyze the differences in the frequency of sex among groups. All statistical analyses were conducted using SPSS software version 11.0 (SPSS, Inc., Chicago, Illinois, USA). Two-sided significance tests were used throughout at an alpha of 0.05.
Demographic and clinical characteristics of the 82 eyes of 82 POAG subjects (male/female: 39/43, aged 27 to 68 years, mean (49±11) years) included in the study are shown in Table 1. There was no statistical significance among groups regarding the subject’s sex and age.
Table 1 shows IOP and fluctuation over 24 hours of the 3 groups. Group POAG-HM had higher single time IOP at 10 am ((19.76±4.32) mmHg), mean corrected diurnal IOP ((19.66±3.94) mmHg) and mean corrected night IOP ((19.8±4.07) mmHg) than other groups, but the difference was not statistically significant (P >0.05), and group POAG-HM had not greater 24-hour IOP fluctuation at resting conditions ((7.89±3.46) mmHg) than other groups.
Table 2 shows corrected IOP at resting conditions at the seven time points of 10 am, 2 pm, 6 pm, 10 pm, 2 am, 6 am and 8 am of the 3 groups. There was no statistical significance of IOP at each time point among groups using ANOVA (P >0.05). Further, using repeated measurement ANOVA, there was no statistical significance among groups regarding the IOPs (P=0.77) and there was no interaction of groups and seven time points (P=0.71), but the difference of IOPs at the seven time points in same group was statistically significant (P=0.01).
Figure 1 shows the nocturnal sitting IOP was higher than the diurnal sitting IOP and the nocturnal sitting IOP was higher in group POAG-HM than that in other groups.
Our results showed that the IOP was higher in POAG patients with high myopia over those POAG alone in three ways: the elevated IOP value was 0.65 mmHg measured in single time IOP at 10 am, 0.84 mmHg in mean corrected 24-hour IOP, 0.97 mmHg in mean corrected night IOP. Similarly, the Blue Mountains Eye Study found mean IOP was approximately 0.5 mmHg higher in myopic eyes than in non-myopic eyes.3 It suggested that POAG patients with high myopia, even on pharmacological glaucoma therapy, still had higher IOP, especially nocturnal
IOP. The 24-hour IOP fluctuation at resting conditions was not different significantly among POAG patients with different degrees of myopia, consistent with Liu et al’s19 finding among young adults with moderate to severe myopia. Our results also showed the difference of IOPs at the seven time points was statistically significant, but this difference was not associated with the degrees of myopia. In addition, the 24-hour IOP fluctuation was lower in the two myopia groups than that in non-myopia group. It suggested that POAG patients with high myopia, even on pharmacological glaucoma therapy, still had a 24-hour IOP fluctuation, but it was lower in patients with myopia than in those without myopia.
Surprisingly, our study subjects were POAG patients with high myopia on only pharmacological glaucoma therapy, while Loewen et al20 showed same outcomes in healthy young adults with hyperopia considering the effect of posture on the IOP. They found that average diurnal sitting IOP was lower in the hyperopia group than that in the myopia group, but the nocturnal supine IOP was higher than the diurnal sitting IOP in two groups and shorter eyes (hyperopia) had a larger 24-hour IOP fluctuation than longer eyes (myopia) in healthy young adults. We and Loewen et al, in patients with high myopia or hyperopia respectively, proved that various refractive status affected IOP and IOP fluctuation.
In addition, there were other effects of high myopia on glaucomatous progression, as following: (1) the fact that high myopia patients were susceptible to glaucoma was first reported by Posner and Scholssman21 in 1948, and was also confirmed by many epidemiology studies4,22,23 after that (2) high myopic eyes have longer axial length,6 larger and/or tilted optic disc, perpapillary atrophy,24 attenuation of the retinal nerve fiber layer (RNFL),25 and insufficient hemoperfusions on the choroid and the retina.26–28 These abnormal anatomical structures are risk factors to POAG.6 (3) Myopia and high IOP had a synergistic effect on the incidence of glaucoma.29 This means that glaucoma patients with myopia had a higher risk in glaucoma development than glaucoma patients alone.
There were several limitations in this study. First, IOP measurements in 24 hours were obtained using NCT and IOP values in this study were after corrected using GAT. We knew that the accuracy and precision of measuring IOP using a NCT in high myopia was worse than that of using GAT.30 The reason for using a NCT was the following: taking IOP measurements 7 times in 24 hours might result in cornea epithelium injury; the long duration of IOP measurement, especially at night, might affect the resting period of the patients, and thus induce an error in measurement of IOP; repeated applanation measurements had been shown to lower IOP on re-measurement.31 Accordingly, the IOP values were approximately the same as their face values. Second, prostaglandin analogue might have had effects on IOP in our study. These effects might potentially mess up the IOP fluctuation and eliminated the effect of high myopia. Finally, the effect of central corneal thickness was not taken into consideration.
In conclusion, high-tension POAG patients with high myopia, even on pharmacological glaucoma therapy, still have higher IOP, but 24-hour IOP fluctuation at resting conditions was lower in these patients.
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