Ophthalmic Surgery, Lasers and Imaging Retina

Clinical Science 

Choroidal Vascularity Index in Retinitis Pigmentosa: An OCT Study

Roy Tan, MMed; Rupesh Agrawal, MD; Swathi Taduru, BsOptom; Arushi Gupta, MBBS; Kiran Vupparaboina, PhD; Jay Chhablani, MS

Abstract

BACKGROUND AND OBJECTIVE:

To evaluate structural changes in the choroid of patients with retinitis pigmentosa (RP) using swept-source optical coherence tomography (OCT) scans.

PATIENTS AND METHODS:

A prospective study was conducted comparing 35 eyes of 35 patients with RP and 26 eyes of 26 normal patients. OCT images of the choroid were binarized into luminal and stromal areas to derive choroidal vascularity index (CVI). Subfoveal choroidal thickness (CT) was also measured and compared.

RESULTS:

There was a significant decrease in the mean CVI among eyes with RP as compared to normal eyes (56.91 ± 1.43% vs. 59.47 ± 1.55%; P < .0001). Mean subfoveal CT was significantly greater in eyes with RP as compared to normal eyes (262.82 μm ± 69.69 μm vs. 194.65 μm ± 23.55 μm; P < .0001).

CONCLUSION:

Patients with RP showed a significant reduction in CVI and an increase in CT as compared to normal eyes.

[Ophthalmic Surg Lasers Imaging Retina. 2018;49:191–197.]

Abstract

BACKGROUND AND OBJECTIVE:

To evaluate structural changes in the choroid of patients with retinitis pigmentosa (RP) using swept-source optical coherence tomography (OCT) scans.

PATIENTS AND METHODS:

A prospective study was conducted comparing 35 eyes of 35 patients with RP and 26 eyes of 26 normal patients. OCT images of the choroid were binarized into luminal and stromal areas to derive choroidal vascularity index (CVI). Subfoveal choroidal thickness (CT) was also measured and compared.

RESULTS:

There was a significant decrease in the mean CVI among eyes with RP as compared to normal eyes (56.91 ± 1.43% vs. 59.47 ± 1.55%; P < .0001). Mean subfoveal CT was significantly greater in eyes with RP as compared to normal eyes (262.82 μm ± 69.69 μm vs. 194.65 μm ± 23.55 μm; P < .0001).

CONCLUSION:

Patients with RP showed a significant reduction in CVI and an increase in CT as compared to normal eyes.

[Ophthalmic Surg Lasers Imaging Retina. 2018;49:191–197.]

Introduction

Retinitis pigmentosa (RP) is an inherited retinal disease that results in progressive deterioration of rod and cone photoreceptors. This process is associated with retinal pigment epithelium (RPE) changes.1 It is thought that RPE cell loss leads to atrophy of choroidal vessels.2 Several studies have reported changes in choroidal structure and thickness in eyes with RP.3–6 Several histopathological studies have confirmed that the reduced ocular blood flow is the primary event (cause) secondary to retinal vessels damage in patients with RP. Narrowing of vessels and sclerosis of vessels, followed by thickening of the blood vessels' walls and consequently luminal occlusion, have been demonstrated as consistent features of RP.7 Histological studies have also shown structural damage of choriocapillaris among patients with RP.7 Fundus fluorescein angiography and indocyanine green angiography have also demonstrated abnormalities in choroidal vessels among patients with RP.7

With the advent of optical coherence tomography (OCT) with enhanced depth imaging (EDI), there has been much interest in studying the angioarchitectural changes of the choroidal layer.8 In patients with RP, it has been shown that there is a reduction in the choroidal and retinal blood flow velocity and vascular diameter, correlating with retinal vessel attenuation and tortuosity.9

There are recent publications describing choroidal vascular changes in various retinal diseases such as age-related macular degeneration (AMD)10 and diabetic retinopathy (DR).11 Our group introduced a relatively novel application of image binarization for EDI-OCT images to compute choroidal vascularity index (CVI), providing a more detailed understanding of the choroidal structures.12,13 This technique has previously been used to study other conditions that affect the choroidal layer and has been shown to be more robust and less variable as compared to choroidal thickness (CT) measurements.14–18

There is limited understanding of choroidal vascular changes in patients with RP. Using swept-source OCT (SS-OCT) scans, our study aims to analyze the choroidal structural changes in eyes with RP and its correlation to CT and visual acuity (VA).

Patients and Methods

Study Population

We conducted a cross-sectional study looking at 35 patients with RP and 26 matched healthy controls. The study period was from July 2016 through January 2017 at a tertiary referral eye care institute in Southern India. Prior approval was obtained from the institutional review board.

Medical records of patients with diagnosis of RP and SS-OCT scans were retrieved and analyzed further. Diagnosis of RP was based on history of nyctalopia, restricted peripheral vision, dilated fundus examination with or without visual field testing, and electroretinography. Not all patients had visual field and electrophysiology studies. Patients with inability to fixate, pathological myopia (−6 diopters or more), systemic illness (eg, diabetes, hypertension), or any other ocular or systemic diseases were excluded from this study. The control group included age-matched heathy subjects' data and OCT scans from the normative database. Demographic details and VA for all the patients and healthy controls were recorded.

Imaging of the Choroid

Images of the choroid obtained via SS-OCT scan using DRI-OCT Triton (Topcon, Tokyo, Japan) (Figure 1A) were retrieved. It utilizes a 1,050-nm wavelength light source, a scanning speed of 100,000 A-scans/second, and an axial and transversal resolution of 7 μm and 20 μm in tissue, respectively. Scans were obtained using our protocol, which included 256 scans over a 6 × 6 mm2 area of the macula. The entire volume scans were extracted for further analysis. Subfoveal CT measurements were derived from the OCT machine.

(A) Representative swept-source scan passing through fovea of a patient with retinitis pigmentosa. (B) The automated choroidal segmentation. (C) The binarized image of the scan.

Figure 1.

(A) Representative swept-source scan passing through fovea of a patient with retinitis pigmentosa. (B) The automated choroidal segmentation. (C) The binarized image of the scan.

Image Binarization

We used an automated algorithm to analyze choroidal vascularity, as described before by our group.14,15 Briefly, choroidal stroma and vessel area analysis involved (i) automated binarization of the OCT B-scans and (ii) automated segmentation of the binarized choroid layer. The task of automated binarization involved (a) preprocessing, (b) exponential and non-linear enhancement, and (c) thresholding.

Finally, the binarized choroid layer was used to quantify the stromal area and vessel area, and CVI was derived (vessel: [stromal + vessel] area ratio) (Figures 1B and 1C). The automated algorithm was applied on total choroidal scans to get the CVI across the entire volume of the choroid.

Visual Field and Electrophysiology

Visual field and electrophysiology were not performed for all the patients. Furthermore, as the available visual field and electrophysiology studies were not obtained at the same time as SS-OCT scans, neither of these variables were considered for further correlation with CVI and VA.

Statistical Analysis

Demographic parameters, best-corrected VA (BCVA), subfoveal CT, and volume CVI were obtained. Baseline characteristics like age, gender, and BCVA were compared between normal and affected eyes. The mean CT as well as CVI were compared between two eye categories using t-test for independent samples. These variables were adjusted with covariates age and gender using analysis of covariance (ANCOVA), and the adjusted variables were compared between the two groups. The correlation of CVI and CT with BCVA was also studied using Pearson's correlation coefficient. All analyses were performed using SPSS version 20.0 (IBM, Armonk, NY), and statistical significance was tested at 5%.

Results

Comparison of baseline characteristics of the patients is shown in Table 1.

Descriptive Statistics for Baseline Characteristics of Patients

Table 1:

Descriptive Statistics for Baseline Characteristics of Patients

Mean CT for the study group was significantly higher than that of the normal group. Mean CVI in eyes with RP was significantly lower than that of normal eyes (Table 2).

Unadjusted and Adjusted Means of Choroidal Parameters for Normal and Study Eyes

Table 2:

Unadjusted and Adjusted Means of Choroidal Parameters for Normal and Study Eyes

Although baseline characteristics like age and gender were insignificantly different in the two groups, mean age in the normal group was higher than in the study group. To understand if this age difference has any influence on the parameters of interest (ie, CT and CVI), one-way ANCOVA was performed with the adjusted means shown in Table 2. The change in mean values of the parameters after adjustment was around 1%, implying limited influence of covariates on the parameters.

The relationship of VA with CT and CVI was obtained using Pearson's correlation coefficient. The correlation between CT and BCVA was positive but statistically insignificant, with coefficient 0.11 (P = .4) (Figure 2A). The correlation of CVI and BCVA was negative but statistically insignificant, with coefficient −0.048 (P = .713) (Figure 2B). A statistically significant negative correlation was observed between CT and CVI, with a coefficient of −0.422 (P = .001) (Figure 3).

Scatter plots showing overall relationship of choroidal thickness (A) and choroidal vascularity index (B) with best-corrected visual acuity.

Figure 2.

Scatter plots showing overall relationship of choroidal thickness (A) and choroidal vascularity index (B) with best-corrected visual acuity.

Scatter plot showing the relationship between choroidal thickness and choroidal vascularity index.

Figure 3.

Scatter plot showing the relationship between choroidal thickness and choroidal vascularity index.

Discussion

Recently, there has been much interest in studying the choroid in various retinal pathologies.19 With EDI-OCT, a noninvasive in vivo study of the choroid can be performed.20 Various studies have been conducted to analyze the CT in patients with RP using EDI-OCT.3–6,21 However, there is no definite consensus of CT in patients with RP. Chhablani et al.21 have shown no significant difference in CT between RP and normal eyes, and correlation of CT with age but not with vision or outer retinal structures in eyes with RP. In contrast, Ayton et al.4 and Dhoot et al.6 showed decrease in CT in eyes with RP. In the current study, we found statistically significant difference in CT between the two groups and this further adds to the existing inconclusive nature of CT in patients with RP among the current literature. This inconsistency in the literature and our study may be the result of CT being influence by systemic and ocular variables such as age, axial length, intraocular pressure, and blood pressure.14

In our study, we additionally computed CVI, which is a relatively novel tool that describes choroidal vasculature.12,13 Unlike CT, CVI is independent of the systemic and ocular factors mentioned above,13 making it a more robust tool in monitoring choroidal changes in RP. Our study showed that eyes with RP have reduced CVI as compared to normal eyes. A similar study by Kawano et al.,5 also using a binarization technique, showed that the luminal (vascular) areas of the choroid in eyes with RP were significantly smaller than that in normal eyes, whereas the stromal areas of the choroid in RP eyes were not significantly different from that in normal eyes. This supports our result of decreased CVI among eyes with RP. Histopathological studies have demonstrated changes in retinal vasculature preceding pigmentary retinal changes and functional changes.7 The reduction in choroidal vascular density can either be a cause or an effect of retinal vascular and structural changes in the retina.

In RP, the death of the photoreceptors leads to the migration of the neighboring RPE cells from the Bruch's membrane. These RPE cells migrate to the inner retina forming bony spicule pigments.22 It is believed that either the death of the photoreceptors or the loss of the RPE cells results in the loss of the adjacent choriocapillaries.22 We postulate that not only the choriocapillary layer is involved, but the larger choroidal vessels in the Haller's and Sattler's layers are involved, which explains the decrease in CVI. In addition, studies have shown a decrease in choroidal blood flow in patients with RP, which may be a cause or effect of the reduced choroidal vessels.23 However, with the current study, it will be difficult to establish a causal association between choroidal vascularity and structural changes in the retina among patients with RP, and further studies are warranted.

In consideration for future treatments for RP, photoreceptors and RPE cells transplantation may be impeded by an impaired choroidal vascularity. The choroid layer is essential for the survival of transplanted photoreceptors and RPE cells.24 It is unknown if the impaired choroid layer can be reestablished after relocation of the RPE. Hence, stringent selection of patients with adequate choroidal layer may be necessary, as a suitability requirement for transplant. CVI can play an important role in this selection and follow-up tool. Furthermore, future advancement of medical therapy in re-establishing the choroidal flow25 can use CVI as a marker to determine the adequacy of the choroid vascularity.

CVI also has possible potential to be a surrogate marker in monitoring and analyzing the progression of RP. It can also potentially be used to diagnose RP in the early stages before the presence of clinical signs. However, further prospective cohort studies will be needed to analyze this potential.

In our study, CT among patients with RP are greater than those in normal patients. We postulate that it may be due to remodeling of the choroidal structure in patients with RP, leading to fibrotic changes that results in an increase in the stromal structure of the choroid relative to the vascular structure. Hence this leads to an increase in CT and a decrease in CVI. There is no histopathological study of the choroid supporting our postulation due to the technical challenges faced in choroidal vascular histological analysis. However, the histopathological studies present in the literature suggest reduced vascularity preceding retinal changes in RP. Our current noninvasive analysis of the choroid along with similar study from Kawano et al.5 support our hypothesis of reduced vascular channels in the choroid. Another possibility may be due to other confounding factors affecting CT, as mentioned above (ie, age, axial length, intraocular pressure, and blood pressure).14

Limitations of this study include the lack of categorizing patients with RP base on their severity or RP genetic subtypes. Also, we could not correlate the changes in CVI with visual field and electrophysiological changes as the imaging study was not performed concurrently and that may hence lead to inaccurate correlation with CVI. This being a cross-sectional study instead of a longitudinal study limits the analysis of the progression in CVI or CT as the severity of RP worsens. Strengths of this study include the volume scans used for computing CVI, the standardization of the data collection, and use of a robust imaging protocol that is reliable and reproducible.13

In conclusion, CVI is a potential noninvasive imaging tool that can be used to monitor choroidal disease in RP. Future research with a larger group of RP patients categorized into the stages of disease or genetic subtypes with concurrent visual field and electrophysiological changes can provide a more in-depth knowledge on the choroidal structural changes and remodeling as the disease progresses.

References

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Descriptive Statistics for Baseline Characteristics of Patients

CharacteristcsEyesP Value
Normal Group (n = 26)Study Group (n = 35)
Age (Years) [M ± SD]40.04 ± 13.1635.26 ± 16.39.212 (NS)
Gender [No. (%)]Male13 (50)17 (48.57).999 (NS)
Female13 (50)18 (51.43).999 (NS)
BCVA (logMAR)0.02 ± 0.100.43 ± 0.60< .001 (S)

Unadjusted and Adjusted Means of Choroidal Parameters for Normal and Study Eyes

Choroidal ParameterUnadjusted M ± SDP ValueAdjusted* M ± SDP Value
Normal Eyes (n = 26)Study Eyes (n = 35)Normal Eyes (n = 26)Study Eyes (n = 35)
Average choroidal thickness (μm)194.65 (23.55)262.83 (69.69)< .001 (S)197.05 ± 23.68261.04 ± 65.61< .001 (S)
Choroidal Vascularity Index (CVI)59.47 (1.55)56.91 (1.43)< .001 (S)59.39 ± 1.4456.97 ± 1.32< .001 (S)
Authors

From the National Healthcare Group Eye Institute, Tan Tock Seng Hospital, Singapore (RT, RA); the School of Material Science and Engineering, Nanyang Technological University, Singapore (RA); L.V. Prasad Eye Institute, Hyderabad, Telangana, India (ST, AG, JC); and the Department of Electrical Engineering, Indian Institute of Technology Hyderabad, Telangana, India (KV).

The authors report no relevant financial disclosures.

Drs. Tan and Agrawal contributed to this manuscript equally as first authors.

Address correspondence to Jay Chhablani, MS, Smt. Kanuri Santhamma Retina Vitreous Centre, L.V. Prasad Eye Institute, Kallam Anji Reddy Campus, Banjara Hills, Hyderabad 500 034 India; email: jay.chhablani@gmail.com.

Received: May 25, 2017
Accepted: November 01, 2017

10.3928/23258160-20180221-07

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