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Editors Selection IGR 10-3

Forms of Glaucoma: Low Perfusion Pressure and NTG Progression Risk

Comment by Gustavo de Moraes on:

76600 Low nocturnal diastolic ocular perfusion pressure as a risk factor for NTG progression: a 5-year prospective study, Raman P; Suliman NB; Zahari M et al., Eye, 2018; 32: 1183-1189

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Raman et al. investigated the predictive value of simultaneous 24-hour intraocular pressure (IOP) and blood pressure (BP) monitoring on visual field progression in normal-tension glaucoma (NTG) patients followed for a minimum of five years. They defined NTG based upon the presence of manifest glaucoma, open angles, and all IOP measurements prior to 24-hour monitoring not exceeding 21 mmHg during office-hours with Goldmann applanation tonometry.

Before coming to the sleep lab, patients underwent a wash-out period and the 24-hour curves were performed on no anti-glaucoma medications. This was done to rule out IOP peaks and misclassification of NTG. IOP and BP measurements were performed every two hours - in the sitting position during the diurnal period and in the supine position during the nocturnal period. Anti-glaucoma medications were re-started after the curves and continued (sometimes modified) during follow-up. In addition, they classified severity based upon the AGIS criteria and defined visual field progression using the modified Anderson criteria as a function of baseline severity. Survival analyses with Kaplan-Meier curves and Cox proportional hazards regression were used to test the association between BP and IOP parameters and an event-based visual field progression endpoint during follow-up.

They found that 35% of patients progressed over the study period with an average mean sensitivity slope of -0.70 ± 1.1 dB/year. In the multivariable analysis, the main predictor of visual field progression was nocturnal diastolic ocular perfusion pressure, which was defined as the difference between the mean diastolic BP and the mean IOP during sleep. Interestingly, they also found that eyes with central field visual field defects at baseline had a 3.5 higher risk of progression than those without it. The main finding, however, was that the cumulative probability of non-progression was 38% at 60 months in patients with diastolic ocular perfusion pressure < 35 mmHg and 88% in those with DOPP > 43.7 mmHg, which translates to a 2.3-fold higher risk among those with lower perfusion (P = 0.01).

The study adds to the current evidence of a strong association between BP, particularly nocturnal BP dips, and glaucoma progression

The study was well-designed and included a very rich database, as many previous studies did not include simultaneous 24-hour IOP and BP monitoring at baseline. Moreover, other studies did not follow all patients for such a long period (five years). The study adds to the current evidence of a strong association between BP, particularly nocturnal BP dips, and glaucoma progression.

One limitation, however, is that the 24-hour IOP monitoring was done after wash-out, thus we cannot infer whether the ocular perfusion estimates reflect the actual perfusion status over the course of follow-up on anti-glaucoma treatment. Therefore, the actual ocular perfusion pressure estimates were likely higher (i.e.: not as severe) than what the study reported during the five years patients were treated. Nonetheless, the study provides compelling evidence that patients with NTG may benefit from 24-hour BP monitoring.

Another interesting finding was the lack of association between BP treatment and visual field progression. Studies have shown that certain types of drugs - and sometimes excessive treatment - could be detrimental to glaucoma patients. Testing or confirming this hypothesis is challenging, however, as studies often lack information on duration of treatment and treatment changes during follow-up. One suggestion to the authors would be to investigate the interaction between drug classes and BP parameters and their association with visual field progression.

The authors should be congratulated for their study and for helping elucidate the relationship between BP, IOP, and glaucoma progression. We now have overwhelming evidence to support future clinical trials testing the hypothesis that BP could be a new modifiable risk factor in glaucoma.

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