FP692 : Does Reduction in Intraocular Pressure Affect the Optic Nerve Head Blood Flow?

Dr. Zia Sultan Pradhan, P13884, Dr.Harsha Rao, Dr. Dhanaraj Rao A S

Zia S. Pradhan, Harsha L. Rao, Dhanaraj A S Rao.

Narayana Nethralaya, Bangalore India

Correspondence: Zia S. Pradhan

+91 81054 15646

zedpradhan@gmail.com

Conflict of interest: none

ABSTRACT:

Purpose:

To determine if reduction in intraocular pressure (IOP) is associated with alterations in the peripapillary and optic nerve head (ONH) vessel density.

Methods: Thirty-eight eyes of 28 patients with ocular hypertension or glaucoma underwent Optical Coherence Tomography (OCT) and OCT Angiography (OCTA) prior to and following IOP reduction with anti-glaucoma medications. The scans were taken within 10 weeks of each other. Multi-level mixed effect modelling was used to determine the factors affecting peripapillary and ONHvessel density.

Results: Mean IOP at the time of initial OCTA was 25mmHg and after IOP reduction was 16mmHg (p<0.001). The change in SSI had a significant positive effect on the peripapillary and ONH vessel density in most sectors of the ONH (coefficient 0.26 to 0.83; p<0.01). Change in IOP did not significantly affect the peripapillary vessel densities, but did show a significant negative association with the optic nerve head vessel (inside disc) densities (coefficient -0.11 to -0.22)

Conclusions: Interpretation of alterations in vessel density should factor in the SSI of the images.  Reduction in IOP does not affect the peripapillary vessel density, but does result in an increase in the vessel density within the optic nerve head.

TEXT:

INTRODUCTION:

Glaucoma is a chronic, progressive optic neuropathy
characterized by optic disc changes and retinal nerve fiber layer (RNFL) defects with associated visual field loss. The pathogenesis is believed to be multifactorial with intraocular pressure (IOP) being the main risk factor. [1]A significant portion of glaucoma patients, however, never have a documented increase in IOP. To explain the development of glaucoma in these patients several theories have been postulated, one of which is the vascular theory. [1-3]Here, the axonal loss is believed to occur due to a reduction in the ocular blood flow due to systemic or local factors. [3] Although a lot of mechanisms have been proposed to explain the optic disc damage inpatients with normal tension glaucoma, a reduction in IOP in these eyes has been found to slow the progression of the disease. [4]This highlights the interplay of IOP and optic nerve head perfusion in the pathogenesis of glaucoma.

The distortion of the lamina cribrosa in response to acute changes in IOP has been well studied in animal and human cadaveric eyes. [5] Unlike the structural changes, the effect of change in IOP on the optic nerve head blood flow has not been well demonstrated in these in vitro models. The recent development of non-invasive imaging of the retinal and optic nerve head vasculature using optical coherence tomography (OCT) technology now allows more in vivo experiments. Using OCT angiography (OCTA), several studies have shown a reduction in the vessel densities in the optic nerve head and peripapillary region in eyes with glaucoma. [6-10] Additionally, several studies have reported good intra- and inter-visit repeatability of the vascular perfusion measurements of OCTA.[6-8,11] However, the literature on the effect of IOP reduction on the optic nerve blood flow is sparse. [12] The purpose of this study was to determine the effect of IOP reduction on the vessel density in the optic nerve head and peripapillary region in eyes with glaucoma or ocular hypertension using OCTA.

METHODS:

This was a prospective, interventional study conducted between May 2015 and October 2016. Ethical clearance was obtained and informed consent taken as per norms.

Participants of the study included untreated or inadequately treated patients with glaucoma or ocular hypertension who required additional IOP lowering medications. Exclusion criteria wererefractive error greater than ±5 D sphere and ±3 D cylinder, presence of any media opacities that prevented good quality OCT images, and any retinal or neurological disease other than glaucoma, which could confound the evaluation. All participants underwent a comprehensive ocular examination at baseline, which included a detailed medical history, best corrected visual acuity measurement, slit-lamp biomicroscopy, Goldmannapplanation tonometry, gonioscopy, dilated fundus examination, stereoscopic optic disc photography conventional OCT and OCTA imaging with RTVue-XR SDOCT.

OCTA imaging uses an 840 nm diode laser source, with an A-scan rate of 70 kHz per second. Optic disc imaging is performed covering an area of 4.5 × 4.5 mm. An orthogonal registration algorithm is used to produce merged 3-dimensional OCT angiograms. [13] The spilt spectrum amplitude-decorrelation angiography (SSADA) algorithm compares the consecutive B-scans at the same location to detect flow using motion contrast, thereby delineating blood vessels.[14]Vessel density is defined as the percentage area occupied by the large vessels and microvasculature in a particular region. Vessel densities are calculated over the entire scan area, i.e. whole enface disc, as well as defined areas within the scan as described below. In addition, the software calculates vessel densities in various layers of the retina and the ONH.

In the optic disc scan, the software automatically fits an ellipse to the optic disc margin and calculates the average vessel density within the ONH (referred to as the inside disc vessel density). The peripapillary region is defined as a 0.75 mm-wide elliptical annulus extending from the optic disc boundary; the average vessel density within this region is calculated. Both the ONH and the peripapillary regions are divided into 6 sectors based on the Garway-Heath map and the vessel densities in each sector is calculated (nasal, inferonasal, inferotemporal, superotemporal, superonasal and temporal sectors). [15]For each scanned region, the software calculates the vessel densities in various layers of the retina and ONH.

IOP lowering medication was initiated for all patients as determined by the glaucoma specialist based on the age, baseline IOP and disease severity. Patients were then reviewed to assess the adequacy of IOP reduction. At this follow-up visit, OCT and OCTA imaging were repeated.  Baseline scans and post-treatment scans were taken not more than 10 weeks apart.

The primary outcome measure was the change in ONH and peripapillary vessel density following IOP reduction which was studied using multi-level mixed effect modelling.

RESULTS:

Sixty-seven eyes with glaucoma or ocular hypertension underwent OCTA before and after IOP reduction. All OCTA and OCT images were reviewed to exclude those of poor quality. The final analysis included 38 eyes of 28 patients. The average duration between the scans was 2 weeks. There was a significant reduction in IOP between the visits (p<0.001)

A comparison of the means of the various OCTA parameters (SSI and vessel density in different regions) showed no difference in the values before and after IOP reduction. A similar analysis done for the structural parameters on OCT showed no difference in the SSI or RNFL parameters, but the total neuro-retinal rim area and inferior neuro-retinal rim area showed a significant increase after IOP reduction.

A significant positive association was seen between the vessel densities in most regions on OCTA and the SSI (co-efficient 0.26 – 0.83) as shown in Table 3. Therefore, an improvement in the SSI was associated with an increase in the vessel density in all regions except the infero-temporal sector within the disc margin. This was accounted for when studying the effect on change in IOP on vessel density using mixed model analysis. These results showed no significant change in the peripapillary vessel densities on IOP reduction. However, certain vessel density measurement within the optic disc margin showed a significant increase in response to IOP lowering. These included the vessel densities in the temporal sector (coefficient -0.19), the Supero-temporal sector (coefficient -0.22) and inside disc region (coefficent -0.11).

A similar analysis based on mixed models was performed on the structural data derived from OCT as shown in Table 3. There was no effect of SSI on the neuroretinal rim area or the peripapillary RNFL thickness. All quadrants of the rim area, however, had a negative association with change in IOP (coefficient -0.001 to -0.01). On the contrary, a positive association was seen between the change in IOP and the change in average and inferior peripapillary RNFL thickness (coefficient 0.06-0.10).

DISCUSSION:

In the recent past, OCT angiography has been used extensively to image the ONH and peripapillary vascular changes in glaucoma. Glaucomatous damage has been shown to be associated with a reduction in the peripapillary vessel densities. [6-10] In the present study, OCT was used to study the effect of IOP reduction on the vascular and structural parameters of the ONH and surrounding peripapillary region.

As noted in previous studies, we found as increase in the rim area on IOP reduction. [16]Both filtering surgery and topical medications have been shown to cause this topographic change in the nerve head. [16-18]  Additionally, we also found an increase in the vessel density within the disc margin following IOP reduction. The effect of IOP on the optic nerve head blood flow has been studied using experimental models and an increase in IOP was found to result in filling defects in the capillary network of the optic disc. [19] Fluorescein Blood Cell Angiography (FBCA) is atechnique that examines the capillary blood flow for each blood component (blood cells and plasma). Using this method, response to IOP elevation was studied in cats and the authors found that if the IOP increased to 45% of the mean systolic blood pressure for 2 hours, it resulted in blood cell stagnation in capillaries within the optic disc. [19]This study is important because it uses labelled blood cells to determine flow which is similar to the principle of motion detection in OCTA, even though the technique is completely different.

The development of OCTA now allows us to image the human ONH vasculature in vivo. The present study showed that there is some increase in the vessel densities of the optic disc following medical reduction in IOP. This may be the result of reperfusion of small capillaries following IOP lowering. In contrast, we found no change in the peripapillary vessel densities on change in IOP. The reason for the difference in response between papillary and peripapillary vasculature may be in their ability to auto regulate flow. The purpose of autoregulation is to ensure continued flow of blood to essential organs despite fluctuations in perfusion pressure. The peripapillary vessels measured in our study were in the superficial RNFL layer and represent the branches of recurrent retinal arterioles (epipapillaryvessels). [20] The retinal vasculature is shown to have autoregulation similar to that of the brain. [5] This may account for the lack of difference in the peripapillary vessel densities on change in IOP. Although autoregulation of the choroidal vasculature is poorly understood, the optic nerve head is believed to have efficient autoregulation in healthy individuals. [5,20] Impaired autoregulation of the ONH has been implicated in the pathogenesis of glaucoma, and this may explain the change in vessel density seen in the optic head but not in the peripapillary region following IOP reduction in the present study.

There are a few limitations of the study. The diverse population included prevents understanding of the vascular pathophysiology of a particular disease subtype. The study, however, was aimed at looking at the effect of IOP reduction on blood flow, irrespective of the etiology. Another drawback is that blood pressure recording was not performed and therefore, estimation of perfusion pressure and its effect on ONH blood flow could not be analyzed.

In conclusion, the present study has highlighted the importance of SSI in the interpretation of alterations in vessel density in OCTA images.  Reduction in IOP does not affect the peripapillary vessel density, but does result in an increase in the vessel density within the optic nerve head.

REFERENCES:

  1. Ching HS, Harris A, Evans DW, et al. Vascular Aspects in the Pathophysiology of Glaucomatous Optic Neuropathy. SurvOphthalmol 1999; 43: S43 – S50.
  2. Flammer J, Mozaffarieh M. What is the present pathogenetic concept of Glaucomatous Optic Neuropathy? SurvOphthalmol 2007; 52:S162-S173.
  3. Yanagi M, Kawasaki R, Wang JJ, et al. Vascular risk factors in glaucoma: a review. Clin ExperimentOphthalmol 2011; 39: 252-258.
  4. Collaborative Normal-Tension Glaucoma Study Group. Comparison of glaucomatous progression between untreated patients with normal-tension glaucoma and patients with therapeutically reduced intraocular pressures. Am J Ophthalmol 1998; 12:487-497.
  5. Fetchtner RD, Weinreb RN. Mechanisms of optic nerve damage in primary open angle glaucoma. SurvOphthalmol 1994; 39: 23 – 42.
  6. Jia Y, Morrison JC, Tokayer J, et al. Quantitative OCT angiography of optic nerve head blood flow. Biomed Opt Express 2012;3:3127-37.
  7. Jia Y, Wei E, Wang X, et al. Optical coherence tomography angiography of optic disc perfusion in glaucoma. Ophthalmology 2014;121:1322-32.
  8. Wang X, Jiang C, Ko T, et al. Correlation between optic disc perfusion and glaucomatous severity in patients with open-angle glaucoma: an optical coherence tomography angiography study. Graefes Arch ClinExpOphthalmol 2015;253:1557-64.
  9. Leveque PM, Zeboulon P, Brasnu E, et al. Optic Disc Vascularization in Glaucoma: Value of Spectral-Domain Optical Coherence Tomography Angiography. J Ophthalmol 2016;2016:6956717.
  10. Yarmohammadi A, Zangwill LM, Diniz-Filho A, et al. Optical Coherence Tomography Angiography Vessel Density in Healthy, Glaucoma Suspect, and Glaucoma Eyes. Invest Ophthalmol Vis Sci 2016;57:OCT451-9.
  11. Yu J, Jiang C, Wang X, et al. Macular perfusion in healthy Chinese: an optical coherence tomography angiogram study. Invest Ophthalmol Vis Sci 2015;56:3212-7.
  12. Hollo G. Influence of Large Intraocular Pressure reduction on Peripapillary OCT vessel density in Ocular Hypertensive and Glaucoma Eyes. J Glaucoma 2016.
  13. Kraus MF, Potsaid B, Mayer MA, et al. Motion correction in optical coherence tomography volumes on a per A-scan basis using orthogonal scan patterns. Biomed Opt Express 2012;3:1182-99.
  14. Jia Y, Tan O, Tokayer J, et al. Split-spectrum amplitude-decorrelation angiography with optical coherence tomography. Opt Express 2012;20:4710-25.
  15. Garway-Heath DF, Poinoosawmy D, Fitzke FW, Hitchings RA. Mapping the visual field to the optic disc in normal tension glaucoma eyes. Ophthalmology 2000;107:1809-15.
  16. Prata TS, Lima VC, Vasconcelos de Moraes CG, et al. Factors associated with topographic changes of the optic nerve head induced by acute intraocular pressure reduction in glaucoma patients. Eye 2011; 25:201-207.
  17. Raghu N, Pandav SS, Kaushik S, Ichhpujani P, Gupta A. Effect of trabeculectomy on RNFL thickness and optic disc parameters using optical coherence tomography. Eye 2012;26(8):1131-1137. doi:10.1038/eye.2012.115.
  18. Lesk MR, Spaeth GL, Azuara-Blanco A, et al. Reversal of optic disc cupping after glaucoma surgery analyzed with a scanning laser tomograph. Ophthalmology 1999;106(5):1013-1018.
  19. Ben-nun J, Nemet P. Intraocular pressure and blood flow of the optic disk: A Fluorescent Blood Cell Angiography Study. SurvOphthalmol 1995; 39: S33-S39.
  20. Prada D, Harris A, Guidoboni G, et al. Autoregulation and neurovascular coupling in the optic nerve head. SurvOphthalmol 2016; 61: 164-168.

 

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