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Editors Selection IGR 16-4

Epidemiology: Perfusion Pressure and POAG

Comment by Gustavo de Moraes on:

75704 Inter-relationship between ocular perfusion pressure, blood pressure, intraocular pressure profiles and primary open-angle glaucoma: the Singapore Epidemiology of Eye Diseases study, Tham YC; Lim SH; Gupta P et al., British Journal of Ophthalmology, 2018; 0:

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There is growing and compelling evidence that systemic blood pressure (BP) may play a role in the pathogenesis of glaucoma. Population-based studies, randomized clinical trials, and longitudinal observational studies have shown that different BP-related parameters have a significant association with the incidence, prevalence, and progression of glaucomatous damage.

In this large population-based study (the Singapore Epidemiology of Eye Diseases Study), which included 19,587 eyes of 9,877 participants, Tham et al. investigated the relationship between inter-relationship between ocular perfusion pressure (OPP), intraocular pressure (IOP) profiles and primary open-angle glaucoma (POAG) in a multiethnic Asian population. This is an important study as it aims to address limitations and inconsistencies from previous studies by evaluating a larger sample and addressing issues related with how OPP, BP and IOP are analyzed in statistical models testing their relationship with glaucoma prevalence. Another important point is that the Singapore Epidemiology of Eye Diseases Study comprises three major ethnic groups in Singapore (Malays, Indians and Chinese) that represent the majority of the Asian population.

When defining POAG based on the Society of Geographical and Epidemiological Ophthalmology criteria, the authors found a prevalence of 2.1% (213 participants), which is consistent with estimates of glaucoma prevalence in Asia. Moreover, POAG participants were older, more likely to be male, Malays and hypertensive than those without this diagnosis (all P ≤ 0.017). Interestingly, after adjusting for a set of confounders (age, gender, ethnicity, diabetes, body mass index, smoking status and antihypertensive medication), in addition to IOP and IOP-lowering treatment, the authors found no significant association between mean arterial pressure (MAP) and diastolic blood pressure (DBP) profiles and POAG. Nonetheless, eyes in the lowest quartile of mean OPP (MOPP, < 50 mmHg) were 1.96 times more likely to be diagnosed with POAG when compared with eyes in the highest quartile (> 61 mmHg). Similarly, eyes in the lowest quartile of diastolic OPP (DOPP, < 56 mmHg) were 1.78 times more likely to be diagnosed with POAG relative to the highest quartile (> 70 mmHg). Of note, these associations became non-significant when further adjusting for IOP-lowering treatment and IOP. This finding suggests that the association between MOPP and DOPP and POAG may be largely the result of the use of IOP in the equation used to calculate these parameters; in other words, with regards to diastolic BP parameters, the effect of IOP may be more important than that of the mean arterial pressure or diastolic pressure alone.

On the other hand, when looking at parameters based on the systolic BP, they found that eyes with both low (< 110 mmHg) and high (> 137 mmHg) systolic OPP (SOPP) levels were significantly more likely to be diagnosed with POAG than those in the mid-range group (123-137 mmHg), even after adjusting for IOP and non-IOP-related confounders. In addition, they found that eyes of patients with low levels of systolic BP (SBP, < 124 mmHg) were 1.69 times more likely to have POAG, compared with mid-range SBP levels (138-153 mmHg). This finding suggests that, with regards to systolic BP parameters, the relationship with POAG prevalence follows a 'U'-shaped curve, reflecting higher risk among those with extreme values of SBP and SOPP, regardless of their IOP.

The authors outlined that one potential explanation for their findings was that a low SBP may indirectly compromise ocular blood supply to the ONH - more so than the DBP - causing ischaemic damage to retinal ganglion cells and initiating glaucomatous development. As a result, the authors suggested that the identification of concurrent low SBP and ocular hypertension (IOP > 21 mmHg) may potentially be a clinically-useful parameter to stratify the risk of glaucoma.

In addition to the large sample size and diverse population studied, two relevant strengths of the present study are the fact that the investigators took into account the effects of IOP and IOP-lowering as well as systemic medications. Also, by dividing the groups into nominal categories (low, mid, and high) without an assumption of linearity enabled the authors to detect a 'U'-shaped effect. This is an important message as it allows us to understand why other studies may have failed to find an association between BP parameters and glaucoma. Notwithstanding, the authors did not employ the same approach when investigating the effect of MAP and DBPP. Note, for instance, that in Tables 2 and 3 they defined the reference group as the highest quantile for MAP, MOPP, DBP, and DOPP, but not for SBP and SOPP (for which they used the mid quantile). It would be important to describe what the results would look like had the same approach been applied across BP-related parameters.

As a limitation, the cross-sectional nature of the study and the collection of BP data at a single time-point may limit our ability to determine a causal association and the effects of circadian rhythms, respectively. Nevertheless, this is a milestone paper that provides a better understanding of the relationship between BP, IOP, and POAG prevalence in addition to cementing the need to include BP monitoring to the arsenal of tests employed in glaucoma management.¹

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