Abstract
Background and aim
Glaucoma is one of the leading causes of visual impairment worldwide. Next to intraocular pressure (IOP), vascular factors play a major role in glaucoma. Mindfulness-based stress reduction (MBSR) has been shown to reduce the IOP, normalize the stress biomarkers, modulate gene expression, and also improve the quality of life. This study was aimed to assess the effect of MBSR in optic disc perfusion of patients with primary open angle glaucoma (POAG).
Experimental procedure
POAG patients with controlled IOP (<21 mmHg) were randomised in to intervention group (n = 30) and control group (n = 30). Both the groups continued their routine glaucoma medications while the intervention group practiced 45 min of MBSR every day in addition. IOP and optic disc perfusion using OCT-Angiography were recorded at baseline and at 6 weeks for both the groups.
Results
The mean age of the participants were 53.23 ± 8.4yr in intervention and 50.23 ± 7.3yr in the control group (p = 0.06). All the baseline parameters were comparable in both groups. After MBSR, in the intervention group there was a significant reduction of IOP (p=0.001), increase in circum-papillary vessel density in superior quadrant (15.8%–17.4%, p=0.02) and nasal quadrant (14.2%–16.5%, p=0.01), increase in circum papillary vascular perfusion, in superior quadrant (38.9%–41.1%, p<0.001), in temporal quadrant (42.2%–44.5%, p<0.001), in inferior quadrant (40.1%–43.8%, p<0.001), and in nasal quadrant (40.6%–42.8%, p<0.001). There was also a significant increase in Flux Index after 6weeks (0.38–0.40, p<0.001).
Conclusion
MBSR can reduce barotrauma and improve optic disc perfusion in POAG patients and serve as a useful adjunct to the standard medical therapy.
1. Introduction
Glaucoma is a vision-threatening progressive optic neuropathy with primary open-angle (POAG) predominating other subtypes.1 It is a complex neurodegenerative disorder characterized by progressive degeneration of retinal ganglion cells (RGCs).2 The pathophysiology of glaucoma is multifactorial. Although the RGC death is related to the level of intraocular pressure (IOP), the factors which contribute to its progression are not fully characterized. Among the other contributing factors for glaucoma, vascular factor plays a major role in glaucoma.3 Optic nerve head microcirculation was found to be correlated with visual field defects and nerve fiber loss in glaucoma.4 Oxidative stress can cause trabecular meshwork dysfunction and may play an important role in the pathogenesis of primary open angle glaucoma.5 The current treatment protocol is mainly focused on the reduction of IOP to a level where the glaucoma progression is halted or delayed either by medical or surgical management. Various neuroprotective agents, antioxidants have been tried as add-on therapy in glaucoma with limited success.6,7 Psychological stress can lead to an elevation in oxidative stress, vascular dysregulations,8 elevations in IOP9 decline in parasympathetic activity, and worsen the glaucoma progression. Stress can be the cause as well as the consequence of vision loss in patients with glaucoma.10,11 Mindfulness meditation is an effective and most widely used technique to evoke relaxation responses and normalize the stress biomarkers.12 In primary open angle glaucoma, Mindfulness based stress reduction (MBSR) has been shown to reduce the IOP, normalize the stress biomarkers, modulate gene expression, and also improve the quality of life in glaucoma patients.13, 14, 15
The invention of Optical coherence tomography-angiography (OCT-A) to assess the retinal vascular density in glaucomatous eyes have allowed the objective study of optic nerve head perfusion. Studies have shown a reduced retinal vascular density and blood flow in eyes with primary open-angle glaucoma (POAG) compared to healthy eyes.16 The peripapillary and macular vascular density had a negative correlation with the severity of glaucoma.17 Along with the existing parameters, changes in peripapillary and macular vessel density can also be used to monitor glaucoma progression.
The present study was designed to answer the research question that whether MBSR can help to increase optic disc perfusion in patients with primary open angle glaucoma (assessed using OCT-A).
2. Methods
This is a prospective, randomized, interventional study conducted at a tertiary care centre in North India after obtaining approval from the institute’s ethical committee (IEC, All India Institute of Medical Sciences, New Delhi, Ref. No. IECPG-384) and following the recommendations of the Declaration of Helsinki. Written informed consent was obtained from all the participants. Due to the lack of previous studies to evaluate the effect of MBSR on optic disc perfusion in patients with glaucoma, a convenient sample of 60 patients was decided. Out of 100 patients assessed, 60 patients who fulfilled the criteria were enrolled in the study. Patients were randomized into 2 groups: 30 in the interventional group and 30 in the control group. Randomization was done by computer-based randomization using permuted blocks.
2.1. Study participants
The inclusion criteria were: age >40 years, moderate/severe POAG (according to Hodapp- Parrish-Anderson [HPA] classification) with IOP <21 mmHg with/without topical medical therapy, and best-corrected visual acuity > 6/60 in the better eye. Exclusion criteria were: any co-morbid condition (other than glaucoma) leading to visual loss, previous practice/experience of meditation or yoga in any form, history of ocular surgery in previous 6 months, having chronic systemic diseases like diabetics which could affect OCT-A parameters, medical therapy for any other illnesses, and significant physical/mental disability.
2.2. Baseline parameters assessed
Complete glaucoma workup including IOP, optic disc perfusion using OCT-A was done for participants (both intervention and control group). Baseline vitals (pulse, blood pressure) were also recorded.
OCT-A was performed using Zeiss AngioPlex (Cirrus HD-OCT 5000, Zeiss Meditec. Inc.). The enface images of the optic nerve head for vessel density and vessel perfusion were calculated in a 6 × 6 mm scan. Three circle scans were drawn on the enface image with a diameter of 1 mm, 3 mm, and 6 mm. 3 mm circle scan was divided into four sectors; superior, temporal, inferior, and nasal. The circumpapillary vessel density (cpVD) and circumpapillary vessel perfusion (cpVP) were calculated in the 3 mm circle scans in all four quadrants. The vessel density was defined as the total length of perfused vasculature per unit area in the region of measurement. The vessel perfusion was defined as the total area of perfused vasculature per unit area of measurement. Using a 4.5∗4.5 mm scan we also measured the flux index of all patients. Flux Index indicates the number of blood cells passing through a retinal vessel cross-sectional area per unit of time. The blood flux index can be defined as the mean flow intensity in the vessel area, where the blood flow signal was normalized from 0 to 1 by dividing by the full dynamic range of blood flow signal intensity. Flux Index is a unit-less ratio.
2.3. Intervention
In the intervention group, the patients underwent a 6 weeks course of MBSR for 45 min under a certified YOGA instructor. No change was done to the standard glaucoma treatment of any patient. The session was for 45 min every day in the morning between 9 a.m. and 10 a.m. The Control group was continued on regular glaucoma medications.
After 6 weeks of IOP, optic disc perfusion and other parameters were recorded for the participants. The control group was also waitlisted for MBSR after the completion of the study.
2.4. Statistical analysis
Both eyes of the participants were taken for the analysis. SPSS Software version 26 was used for data analysis. Chi-square test and Fisher’s exact test were employed to compare categorical characteristics at baseline. Independent t-test was used to compare parameters between two groups and paired t-test was used to compare within-group parameters for parametric data. Wilcoxon sign rank test (within-group) and Mann-Whitney test (intergroup) were used for non-parametric data. Spearman correlation test was used to assess correlation. P-value < 0.05 was considered significant.
3. Results
The mean age of the participants (intervention: 53.23 ± 8.4 yr, controls: 50.23 ± 7.3 yr; p = 0.06) were comparable between the two groups. There was male predominance in both the groups with comparable sex distribution (intervention: 4:1, controls: 3.3:1; p = 0.08). The baseline parameters of the eyes (60) like IOP, cup-disk ratio, number of topical glaucoma medications used, mean deviation in the visual field (Humphrey field analyzer, Zeiss, San Leandro, USA) were comparable in both groups (Supplementary Table 1).
3.1. Changes in optic nerve head perfusion
After 6 weeks, a 3 mm circle scan showed a significant increase in cpVD in the superior and nasal quadrant for the intervention group, while there was no significant change in the controls (Table 1). The 3 mm circle scan also showed a significant increase in cpVP in all four quadrants for the intervention group (Fig. 1a and b), while there was no significant change in the controls (Table 1).
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