Is Balancing Blood Pressure Night Dips Effective in Preventing Glaucoma Progression ? A Pilot Study

C l i n M e d International Library Citation: Peretz G, Zalish M (2015) Is Balancing Blood Pressure Night Dips Effective in Preventing Glaucoma Progression? A Pilot Study. Int J Ophthalmol Clin Res 2:045 Received: October 26, 2015: Accepted: December 22, 2015: Published: December 24, 2015 Copyright: © 2015 Peretz G, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Peretz and Zalish. Int J Ophthalmol Clin Res 2015, 2:6 ISSN: 2378-346X


Methods
We did a retrospective chart review of an interventional case series of patients treated at our Glaucoma Unit between 1995-2014.The diagnosis of glaucoma was made by our glaucoma specialists and it was based on the presence of a glaucomatous optic neuropathy in at least one eye, and a glaucomatous visual field (VF) according to a 24-2 or 30-2 Swedish interactive thresholding algorithm (SITA) standard automated perimetry (SAP) examination (SITA-SAP, Humphry visual field analyzer; Carl Zeiss Meditec Inc., Dublin CA).
Inclusion criteria were open anterior chamber angles, no identifiable secondary causes for glaucoma, and progressive glaucoma with IOPs ≤ 12. Patients were categorized as having POAG if their IOPs were > 21 mmHg and NTG if their IOPs were < 21 mmHg at the time of glaucoma diagnosis.Only the glaucomatous eyes from each patient were included in this case series.Glaucoma was considered progressing if 3 adjacent points were considered progressing with a p-value < 0.05 in the glaucoma change probability analysis in 3 consecutive visual fields (a method based on the EMGT study [15]).All patients included in this case series were instructed to perform a 24-hour BP Holter monitor assessment in order to determine the presence of night dips.Physiologic night dips were diagnosed if nocturnal mean BP measurements (either mean systolic, mean diastolic, or mean BP) were between 10-20% lower than BP measurements during waking hours.Extreme night dips were diagnosed if nocturnal values were > 20% lower than values during waking hours [13].The family physicians were advised to lower the extent of the night dips by changing the medical treatment or the time of administration only for the patients with extreme nocturnal BP dips.We then conducted a long-term follow-up of these patients in order to determine whether

Introduction
Much has been written about the relationship between intraocular pressure (IOP) and glaucoma.An elevated IOP has been found to be a risk factor for both glaucoma development and progression, and IOP reduction has been useful in at least slowing disease progression [1][2][3][4].Some glaucoma patients continue to progress in spite of having low IOP levels, and this applies to treated patients with primary open angle glaucoma (POAG) as well as treated patients with normal tension glaucoma (NTG).This progression has been explained by mechanisms other than IOP reduction.One theory involved decreased ocular perfusion.It was shown that low blood pressure (BP) levels, and especially low nocturnal BPs (night dips), are related of their IOP stopped their glaucoma progression.We therefore feel more confident to provide additional IOP-lowering interventions to patients who are not extreme night dippers.
Limitations of our series include the low number of patients and its retrospective nature.Had this been a prospective study, we would have requested a second Holter assessment after the medical interventions were carried out by the family physician in order to verify the reduction of the night dips.Larger prospective studies are needed to establish our observation.In conclusion, we believe that normalizing extreme night dips in progressing glaucoma patients with low IOPs may be effective in stopping progression.We recommend further lowering of the IOPs in progressing glaucoma patients who are not extreme night dippers.they were still progressing after this intervention.The ethical review board of our institution approved this retrospective study, and the tenets of the Declaration of Helsinki were followed.Informed consent was waived.

Results
Nine patients (16 glaucomatous eyes) were included in the study.Epidemiological characteristics are described in table 1.Three patients were diagnosed as having NTG, and 6 as having POAG.All patients were being treated medically for systemic hypertension, and they were all considered as progressing by at least 3 consecutive visual fields while maintaining IOPs of ≤ 12 mmHg.After undergoing a 24hour BP Holter monitor assessment, 7 patients were considered as being extreme dippers and 2 were considered physiologic dippers (the latter included 1 patient with NTG and 1 with POAG).The family physicians of the 7 extreme dippers were asked to normalize their patients' night dips, and those patients were followed for a period of 1-7.3 years (mean 5.26 years, median 6.25 years).Five of those 7 extreme dippers (71%) did not progress any further during follow-up.The remaining 2 that did progress (1 with NTG and 1 with POAG, one eye in one patient and both eyes in the other) continued to do so even when medical treatment to further lower the IOP had been added.

Discussion
Lowering of the IOP is recognized as the mainstay of glaucoma treatment, but we occasionally encounter patients whose visual field defect continues to progress even though their IOPs are low and are considered to have been normalized.It was proposed that a reduction in optic nerve perfusion might play a role in such situations.Many studies have shown that glaucoma patients who demonstrate systemic BP night dips are prone to visual field deterioration, especially extreme night dippers, patients who are treated for systemic hypertension, and NTG patients [5,8,12,13,16].All the patients in the current series were being treated for systemic hypertension and most of them were diagnosed as being extreme night dippers.
We recommended that all glaucoma patients who were progressing under IOPs of ≤ 12 mmHg undergo 24-hour BP Holter monitor assessment.These patients were using an average of 2.5 topical medications and some even had undergone filtration surgery and/or laser trabeculoplasty.We believe that compliance and side effects affect our ability to add more IOP-lowering medications to patients at this stage of glaucoma treatment.
Five of our 7 (71%) patients who were diagnosed as extreme dippers did not progress after their family physicians reduced their night dips by changing their hypertension medications or the time of administration.This result is in agreement with other studies that suggest that extreme night dips in BP might play a role in glaucoma progression.To the best of our knowledge, however, this is the first report that actually investigates the long-term effect of reducing night dips on glaucoma progression.Two of those 7 (29%) patients continued to progress even though their night dips were reduced, and their progression persisted even when other topical IOPlowering medications were added, suggesting that other mechanisms of glaucomatous injury might be responsible for these therapeutic failures.Two of our 9 (11%) patients who were progressing under IOPs of ≤ 12 mmHg were physiologic dippers, and further reduction

Table 1 :
Epidemiologic characteristics of the study patients.Some patients had filtration surgery and/or laser trabeculoplasty NTG: Normal Tension Glaucoma, POAG: Primary Open Angle Glaucoma *