An Evaluation of Vascular Density Changes by Optical Coherence Tomography Angiography in Patients with Ocular Hypertension

doi:10.21203/rs.3.rs-2007637/v1

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An Evaluation of Vascular Density Changes by Optical Coherence Tomography Angiography in Patients with Ocular Hypertension

https://doi.org/10.21203/rs.3.rs-2007637/v1

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Purpose

To evaluate Optical Coherence Tomography Angiography (OCT-A) findings in patients with Ocular Hypertension (OHT) and compare them with healthy individuals.

Material and Methods

Thirty-four patients with ocular hypertension (OHT) and 22 healthy individuals were included in the study. Foveal thickness, retinal vascular density in superficial and deep capillary plexus and choriocapillaris, foveal avascular zone (FAZ), acircularity index (AI), foveal vessel density (FD), non-flow area, capillary and all vessel densities in the peripapillary area and the disc were automatically measured using the Angiovue software of OCT-A and compared between groups.

Results

The comparison of the macular OCT-A findings did not reveal a significant difference between the two groups in terms of central macular thickness, superficial and deep capillary plexus vessel density (p > 0.05). The foveal avascular zone width was significantly higher in OHT patients compared to the control group (0.30 ± 0.08µ and 0.25 ± 0.11 µ, respectively; p = 0.04). The comparison of optic nerve OCT-A findings revealed that the whole-field vessel density (wVD) (p = 0.007), peripapillary vessel density (pVD) (p = 0.001), inferior, superior and temporal radial peripapillary capillary plexus vessel density (p = 0.006, p = 0.008, p = 0.02) and the mean retinal nerve fiber layer thickness (p = 0.02) were significantly lower in the OHT group.

Conclusion

Our findings suggest that the decrement in the optic disc vascular density and foveal avascular zone width was significantly higher in OHT patients. The possible effect or role of these microvascular changes in terms of glaucoma development should be examined through further studies.

vascular density

ocular hypertension

optical coherence tomography angiography

Glaucoma is the leading cause of irreversible blindness worldwide [1]. Since glaucomatous damage can be prevented but is irreversible, early diagnosis and close follow-up of glaucoma patients are very important. It is known that besides intraocular pressure (IOP), vascular, and hemodynamic factors also play an important role in the development of glaucoma. Ocular hypertension (OHT) is characterized by an intraocular pressure value (IOP) greater than 21 mmHg in the absence of any glaucomatous changes in the optic nerve head and visual field. Studies have shown that approximately 1% of patients with OHT develop glaucoma every year.

Optical coherence tomography angiography (OCT-A) is a recently developed technique that allows a quantitative evaluation of microcirculation in the retina and choroid in a rapid and non-invasive manner. This study aimed to evaluate the peripapillary and macular microvasculature of patients with OHT using OCT-A and to compare the obtained data with the data obtained from healthy individuals.

Thirty-four patients with OHT and 22 age- and gender-matched healthy individuals were included in this study. The study protocol was approved by the Institutional Review Board of Ankara Numune Training and Research Hospital (E-19-2642) and adhered to the tenets of the Declaration of Helsinki. Informed consent was obtained from all participants prior to the enrollment.

Patients with a history of diabetes mellitus, hypertension, cardiovascular disease, and eye disease (such as cataract, macular degeneration, high myopia or hypermetropia, active uveitis, macular edema, or choroidal diseases) which may affect the measurement of retinal vascular density with OCT-A, and those who used drugs, which might affect vascular structures (such as calcium channel blockers, beta-blockers), were excluded from the study.

All patients underwent a detailed ophthalmologic evaluation including measurement of best-corrected visual acuity, slit-lamp biomicroscopy, diurnal intraocular pressure (IOP) measurement with Goldmann applanation tonometer, central corneal thickness measurement with ultrasonic pachymeter (IOPac Advanced Pachymeter, Heidelberg Engineering Inc., Germany) and fundus examination. The diagnosis of OHT was made by two glaucoma specialists (OGK and AY) in the presence of untreated IOP > 21 mmHg (recorded during normal clinic hours at 8 AM, 10 PM, 12 PM, 2 PM and 4 PM during the same day), normal Humphrey 30 − 2 visual field test. A minimum of two reliable normal visual fields, defined as a pattern standard deviation (PSD) within 95% confidence limits and a glaucoma hemifield test (GHT) result within normal limits. Normal optic disc appearance without glaucomatous changes and open anterior chamber angle by gonioscopy.

The microvascular structure in the macula was evaluated with 6x6 mm OCT-A (Optovue, Inc., Freemont, CA) and the microvascular structure in the optic nerve area was evaluated with 4.5x4.5 mm OCTA. Mean retinal nerve fiber layer (RNFL) thickness was evaluated with the same OCT (Figs. 1 and 2).

Statistical analysis was performed using SPSS ver. 17.0 (Chicago, IL, USA). The categorical variables were analyzed by the Pearson X2 test. Mann-Whitney U test was used to compare the RNFL thickness, macular and peripapillary OCT-A measurements in patients with OHT and healthy controls. A p-value of less than 0.05 was accepted as statistically significant.

Thirty-four eyes of the 34 patients with OHT and 22 eyes of 22 healthy controls were included in this study. The mean age of patients with OHT was 52.3 ± 5.4 and the mean age of healthy controls was 50.4 ± 3.5 years. There was no statistically significant difference in the mean age (p = 0.1), gender (p = 0.5) of the two groups. The central macular thickness was found to be 249.9 ± 23.1 µ in the OHT group, and 259.2 ± 17.4 µ (p = 0.07) in the Control group, which was not statistically significant. The retinal nerve fiber layer thickness was determined to be significantly lower in the OHT group (106.7 ± 10.5 µ) than in the control group (115.9 ± 11.8 µ) (p = 0.02). Detailed demographic characteristics of the study groups can be found in Table 1.

Table 1

Clinical and demographic characteristics of the study groups
	Ocular Hypertension (n = 34)	Control (n = 22)	p
Age (years)	52.3±5.4	50.4±3.5	0.1
Gender, F/M	23/11	13/9	0.5
Intraocular pressure (mmHg)	23.8±1.5	16.3±1.9
Central Macular Thickness (µ)	249.9±23.1	259.2±17.4	0.07
Retinal nerve fiber layer thickness (µ)	106.7±10.5	115.9±11.8	0.02

When the macular OCTA findings were examined, the Foveal avascular zone (FAZ) area was significantly higher in OHT patients compared to the control group (0.30 ± 0.08µ and 0.25 ± 0.11µ respectively; p = 0.04) (Table 2). The mean RNFL thickness was lower in the OHT group (p = 0.02). No statistically significant difference was found between the two groups in terms of central macular thickness, superficial and deep capillary plexus vessel density (p > 0.05).

Table 2

Macular OCT-A findings in ocular hypertension and control groups
	Ocular Hypertension (n = 34)	Control (n = 22)	p
CMT (µ)	249.91±23.08	259.23±17.46	0.07
SCP foveal VD (%)	17.31±6.66	19.69±6.68	0.17
SCP parafoveal VD (%)	47.31±5.76	48.58±4.45	0.54
SCP perifoveal VD (%)	46.83±4.18	48.33±3.45	0.23
DCP foveal VD (%)	33.85±7.37	36.21±7.75	0.21
DCP parafoveal VD (%)	52.78±5.01	50.33±5.76	0.36
DCP perifoveal VD (%)	48.01±7.07	46.42±3.70	0.50
FAZ area (mm2)	0.30±0.08	0.25±0.11	0.04
FAZ perimetry (mm)	2.13±0.28	1.93±0.42	0.05
AI	1.1±0.03	1.1±0.04	0.48
FD-300 (%)	50.78±7.39	50.07±4.56	0.26
Area without flow	0.60±0.22	0.51±0.14	0.12
AI: acirculatory index; VD: vein density; DCP: deep capillary plexus; FAZ: foveal avascular zone; CMT: central macular thickness; SCP: superficial capillary plexus, Mann-Whitney-U test used for the statistical significancy (P < 0.05).

The optic nerve OCT-A findings are summarized in Table 3. The mean whole image vessel density (wiVD) and peripapillary vessel density (VD) were significantly lower in the OHT group than the control group (p = 0.007 and p = 0.001; respectively). The average vessel densities in the inferior, temporal and superior quadrants were also significantly lower in the eyes with OHT (p = 0.006, p = 0.008, p = 0.025; respectively).

Table 3

OCTA findings of the optic disc in ocular hypertension and control groups
	Ocular Hypertension (n = 34)	Control (n = 22)	p
Whole image VD	49.04±2.27	50.84±1.91	0.007
Inside disc VD	46.17±5.29	46.33±4.77	0.88
Peripapillary VD	52.17±2.85	54.7±1.55	0.001
Nasal VD	52.78±5.45	52.47±4.13	0.73
Inferior VD	53.77±4.72	56.42±2.65	0.006
Temporal VD	51.45±5.47	55.26±3.12	0.008
Superior VD	53.09±5.25	55.95±2.61	0.025
VD: vessel density, Mann-Whitney-U test used for the statistical significancy (P < 0.05).

The OCT-A is a novel non-invasive imaging method that detects blood flow from the motion contrast of erythrocytes within the vessel [2]. The OCT-A has the potential to bring new insights in glaucoma diagnosis and follow-up as it allows the evaluation of microvascular structures both qualitatively and quantitatively [3]. Recent studies have reported that macular superficial plexus vessel density was lower in glaucomatous eyes compared to normal eyes [4, 5, 6]. Such changes in retinal microvasculature can be associated with structural changes in the early stages of glaucoma.

There are not many studies investigating FAZ width in OHT patients in the literature. In their study, Chao et al. found no significant difference in FAZ width between OHT and control groups [7]. In his study, Yener found no significant difference between OHT patients and the control group [8]. In contrast to these studies, in our study, the foveal avascular zone was found to be wider in the OHT group. Chihara et al. found that the vascular density in the superficial peripapillary retina was lower in OHT patients than in the healthy control group [9]. Here they commented that the blood supply is decreasing. Since the fovea is avascular and receives its nutrition from neighboring structures, it is affected by ischemia resulting from the deterioration of the surrounding vascular nutrition. This is manifested by the expansion of the avascular structure in the fovea. Also, Chao et al. found significant FAZ enlargement in OAG and NT glaucoma compared to OHT and normal healthy individuals. They commended that FAZ enlargement can be an early sign of glaucomatous damage [7]. Considering that OHT patients progress to glaucoma, the FAZ enlargement we obtained from our study may be an early sign of glaucoma progression in OHT patients.

No significant difference was found between the two groups in terms of central macular thickness, superficial and deep capillary plexus vessel density. The OCTA findings of the optic nerve head were examined, it was found that the whole image vessel density, peripapillary vessel density, inferior, temporal and superior radial peripapillary capillaries (RPC) vessel density were significantly lower in the OHT group compared to the control group.

Jia et al. used OCTA in cases with glaucoma for the first time and detected decreased vascular density in the glaucoma group, more in the temporal region, by measuring the optic nerve head vascularity [10].

Chen et al., in their study, found a lower nasal-inferior and temporal RPC-VD and a borderline level of negative correlation with IOP more than 21 mmHg in Juvenil OHT. They suggested that peripapillary scans should be analyzed individually based on different levels of cup-disc ratio [11].

Yarmohammadi et al. investigated peripapillary vessel density and RNFL in primary open-angle glaucoma cases, glaucoma suspects cases, and healthy volunteers. As a result, they determined the thinnest vein density in the primary open-angle glaucoma group, then in the glaucoma suspects, and the thickest vein density was shown in the healthy control group. Similarly, they reported the lowest RNFL thickness in the primary open-angle glaucoma group and then in the ocular hypertension group and the highest RNFL thickness in the healthy control group [12].

Köse et al. reported that there was no statistically significant difference between peripapillary vessel density and RNFL between the OHT and control groups, but there was a decrease in the superficial and deep plexus vessel density in the OHT group [13].

Chihara et al., similarly, investigated peripapillary vessel density, optic disc prelaminar flow index, and RNFL thickness in primary open-angle glaucoma cases, ocular hypertension cases, and healthy volunteers. They found that peripapillary vessel density, optic disc prelaminar flow index, and RNFL thickness were significantly lower in glaucoma patients than in healthy volunteers, while they found only the peripapillary vessel density to be lower in OHT patients, and reported similar optic disc prelaminar flow index and RNFL thickness values. They reported that peripapillary vessel density was more effective in distinguishing glaucoma and ocular hypertension cases [9].

Hollo et al. investigated the peripapillary vessel density and RNFL in primary open-angle glaucoma cases, ocular hypertension cases, and healthy volunteers and suggested that peripapillary angioflow density measurements can identify decreased peripapillary perfusion early in the glaucomatous RNFL thinning process, prior to the development of clinically significant RNFL damage and visual field deterioration [14].

In this study, similar to previous studies, peripapillary and whole-area vessel density and radial peripapillary capillary plexus vessel density in the other three quadrants except the nasal quadrant were found to be statistically significantly lower in the OHT group. Current findings suggest reduced vascular density in ocular hypertension patients without further glaucomatous changes.

As a result, the optic disc vascular density decreases in OHT cases. We think that using OCT-A in OHT and glaucoma follow-up may provide early diagnosis and treatment in these patients. However, further studies are needed to investigate the effect of microvascular changes seen in these cases on the prognosis in terms of glaucoma development.

Conflict of Interest The authors declare that they have no conflict of interest.

Funding None.

Author Contributions Dr. S Çomçalı and Dr P Topçu Yılmaz- Data collection,wrote the main manuscript text, submission manuscript and statistical analysis; Dr. Ç Coşkun, Dr. C Çavdarlı, Dr. Ö Gürbüz Köz, Dr. A Yarangümeli and Dr. E Yıldız Özdemir – Coordination, data collection, prepared figures , Manuscript Editing and Consultants to the procedure.All authors reviewed the manuscript.

Data availability The manuscript has no associated data in a data repository.

Animal Research This article does not contain any studies with animals performed by any of the authors.

Consent to Participate Informed consent was obtained from all individual participants included in the study.

Consent to Publish Informed consent for potential research publication was obtained from all individual participants included in the study at the time of their treatments performed.

Ethical approval All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee (Ankara Numune Education and Research Hospital E-19-2642) and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

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No competing interests reported.

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An Evaluation of Vascular Density Changes by Optical Coherence Tomography Angiography in Patients with Ocular Hypertension

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Abstract

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Material and Methods

Results

Conclusion

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Introduction

Materials And Methods

Results

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