Journal of Pediatric Ophthalmology and Strabismus

Original Article 

Analysis of Macular Vessel Density and Foveal Avascular Zone Using Spectral-Domain Optical Coherence Tomography Angiography in Children With Amblyopia

Bengi Demirayak, MD, FEBO; Asli Vural, MD, FEBO; Ismail Umut Onur, MD, FEBO; Fatma Selin Kaya, MD, FEBO; Fadime Ulviye Yigit, MD

Abstract

Purpose:

To quantify the foveal avascular zone and the whole, parafoveal, and foveal vessel density of superficial and deep capillary plexus in amblyopic eyes and age-matched controls and to compare the measurements.

Methods:

This cross-sectional study involved 49 eyes from 17 patients with amblyopia and 21 healthy children (aged 6 to 16 years). Optical coherence tomography angiography was performed for all participants and superficial capillary plexus, deep capillary plexus, and foveal avascular zone were evaluated. Data from amblyopic eyes, fellow eyes with unilateral amblyopia, and control eyes were compared using the Mann–Whitney U test.

Results:

The mean patient age was 8.6 ± 2.5 years in the amblyopia group and 9.6 ± 2.9 years in the control group. The mean foveal avascular zone measurements were 0.251 ± 0.1 mm2 in the amblyopia group and 0.291 ± 0.1 mm2 in the control group. The whole, foveal, and parafoveal vessel densities of superficial capillary plexus were 48.8% ± 3.7%, 23.8% ± 8.8%, and 50.9% ± 4.6% in the amblyopia group and 48.4% ± 2.5%, 19.3% ± 5.4%, and 51.3% ± 2.7% in the control group. The whole, foveal, and parafoveal vessel densities of deep capillary plexus were 51.8% ± 4.3%, 37.6% ± 5.8%, and 54.8% ± 4.2% in the amblyopia group and 54.4% ± 3.2%, 34.9% ± 7.4%, and 56.8% ± 3.2% in the control group. No statistically significant difference was detected in all measurements.

Conclusions:

Assessment of the foveal avascular zone and vessel density of superficial capillary plexus and deep capillary plexus with optical coherence tomography angiography revealed no difference between amblyopic eyes, controls, and fellow eyes of patients with unilateral amblyopia.

[J Pediatr Ophthalmol Strabismus. 201X;X(X):XX–XX.]

Abstract

Purpose:

To quantify the foveal avascular zone and the whole, parafoveal, and foveal vessel density of superficial and deep capillary plexus in amblyopic eyes and age-matched controls and to compare the measurements.

Methods:

This cross-sectional study involved 49 eyes from 17 patients with amblyopia and 21 healthy children (aged 6 to 16 years). Optical coherence tomography angiography was performed for all participants and superficial capillary plexus, deep capillary plexus, and foveal avascular zone were evaluated. Data from amblyopic eyes, fellow eyes with unilateral amblyopia, and control eyes were compared using the Mann–Whitney U test.

Results:

The mean patient age was 8.6 ± 2.5 years in the amblyopia group and 9.6 ± 2.9 years in the control group. The mean foveal avascular zone measurements were 0.251 ± 0.1 mm2 in the amblyopia group and 0.291 ± 0.1 mm2 in the control group. The whole, foveal, and parafoveal vessel densities of superficial capillary plexus were 48.8% ± 3.7%, 23.8% ± 8.8%, and 50.9% ± 4.6% in the amblyopia group and 48.4% ± 2.5%, 19.3% ± 5.4%, and 51.3% ± 2.7% in the control group. The whole, foveal, and parafoveal vessel densities of deep capillary plexus were 51.8% ± 4.3%, 37.6% ± 5.8%, and 54.8% ± 4.2% in the amblyopia group and 54.4% ± 3.2%, 34.9% ± 7.4%, and 56.8% ± 3.2% in the control group. No statistically significant difference was detected in all measurements.

Conclusions:

Assessment of the foveal avascular zone and vessel density of superficial capillary plexus and deep capillary plexus with optical coherence tomography angiography revealed no difference between amblyopic eyes, controls, and fellow eyes of patients with unilateral amblyopia.

[J Pediatr Ophthalmol Strabismus. 201X;X(X):XX–XX.]

Introduction

Amblyopia is a visual disorder characterized by subnormal visual acuity and contrast sensitivity in one or both eyes. It is caused by either visual deprivation or abnormal binocular interactions.1 Recently, some authors have shown that the amblyopic process may involve the choroid and the macula by using objective quantitative optical coherence tomography (OCT) measurements. Kara et al.2 reported that amblyopic eyes had a significantly thicker choroid than control eyes. Kasem and Badawi3 also demonstrated that higher central macular thickness and thicker global retinal nerve fiber layer were present in unilateral amblyopic eyes compared to those of the healthy fellow eyes.

Recently, OCT angiography, which is a relatively new and non-invasive imaging technique, has been used to visualize the retinal microvasculature and foveal avascular zone.4 OCT angiography is capable of detection and measurement of intravascular erythrocyte movement and provides three-dimensional maps of the macular perfusion.5 Two studies in the literature were conducted in children with amblyopia using OCT angiography.6,7 Both of these studies showed that amblyopic eyes had lower macular capillary densities. The purpose of our study was to evaluate and compare measurements of macular vessel density and foveal avascular zone using OCT angiography in amblyopic eyes and age-matched controls and to determine whether our results were concordant with the previous two studies.

Patients and Methods

This cross-sectional, comparative study was conducted in Bakirköy Dr. Sadi Konuk Training and Research Hospital, Istanbul, Turkey. The study was approved by the ethics committee of Bakirköy Dr. Sadi Konuk Training and Research Hospital and adhered to the tenets of the Declaration of Helsinki. Participants were recruited from patients aged 6 to 16 years presenting to our clinic.

Amblyopia was defined as visual acuity of 20/30 or worse or a difference of two or more lines on the Snellen chart between the better and worse eye without an organic cause for the decreased vision. Only amblyopia due to strabismus or anisometropia was included. In bilateral amblyopia, the eye with poorer vision was selected. Children who presented to our clinic with 20/20 best corrected visual acuity (BCVA) and no evidence of any ocular abnormality were enrolled in the normal control group. We selected the right eye only for analysis to eliminate similarities of the measurements in the same person as a confounding factor.

Patients with deprivation amblyopia, nystagmus, media opacity, history of prematurity, history of ocular or systemic disease, or history of intraocular surgery were excluded. Patients with a spherical refractive error greater than 5.00 diopters (D) were also excluded to avoid these factors influencing OCT measurements.

All participants underwent standard ophthalmologic examinations, including cycloplegic refraction, BCVA, and slit-lamp and fundus examinations. To qualify BCVA, the patients were retested 3 days after cycloplegic refraction and Snellen acuity was measured. Snellen BCVA was converted to logarithm of the minimum angle of resolution (logMAR) units for analysis.

OCT angiography using the split-spectrum amplitude decorrelation angiography algorithm (RTVue XR Avanti with Angio Vue; Optovue, Inc., Fremont, CA) was performed for all participants. A macular 3 × 3 mm scan was used. Each scan was automatically segmented by the software to visualize the superficial capillary plexus and deep capillary plexus of the retina. The whole, foveal, and parafoveal vessel densities (as a percentage) of the superficial capillary plexus and deep capillary plexus, foveal avascular zone area (mm2), and central foveal thickness were analyzed (Figure 1).

Results from 3 × 3 mm macular scans of vessel density of a normal eye. (A) superficial capillary plexus, (B) deep capillary plexus, and (C) foveal avascular zone

Figure 1.

Results from 3 × 3 mm macular scans of vessel density of a normal eye. (A) superficial capillary plexus, (B) deep capillary plexus, and (C) foveal avascular zone

MedCalc Statistical Software (version 12.7.7; MedCalc Software bvba, Ostend, Belgium; http://www.medcalc.org; 2013) was used for data analysis. Categorical variables were recorded as numbers and numerical variables as mean and standard deviation. The Mann–Whitney U test was used to compare values. A P value of less than .05 was considered statistically significant.

Results

A total of 49 eyes of 38 children were included in this study, 17 (44.7%) of which were amblyopic eyes and 21 (55.3%) were control eyes. The mean patient age was 8.6 ± 2.5 years in the amblyopia group and 9.6 ± 2.9 years in the control group. Clinical characteristics of patients and controls were summarized in Table 1.

Clinical Characteristics of the Study Participantsa

Table 1:

Clinical Characteristics of the Study Participants

The whole, foveal, and parafoveal vessel densities of the superficial capillary plexus and deep capillary plexus measurements of participants are shown in Table 2. There was no statistically significant difference between amblyopic eyes and controls. The mean foveal avascular zone measurements were 0.251 ± 0.1 mm2 in the amblyopic group and 0.291 ± 0.1 mm2 in the control group. The difference between groups was not statistically significant (P = .23). The mean subfoveal thickness was 250.6 ± 27.8 µm in the amblyopic group and 244.8 ± 15 µm in the control group. The difference was not significant statistically significant (P = .93).

OCT Angiography Measurements

Table 2:

OCT Angiography Measurements

We also compared 11 amblyopic eyes of patients with unilateral amblyopia with 11 fellow eyes (Table 3). We did not find any significant difference with regard to superficial capillary plexus, deep capillary plexus, foveal avascular zone, and central foveal thickness.

OCT Angiography Measurements of Patients With Unilateral Amblyopia

Table 3:

OCT Angiography Measurements of Patients With Unilateral Amblyopia

Discussion

OCT angiography is a new imaging technology and several studies have verified the reliability and reproducibility of its measurements.8–10 However, most previous studies using OCT angiography mainly included adult patients. Consequently, few studies about children have been reported.11–13 Zhang et al.12 reported that the mean size of the foveal avascular zone was 0.290 mm2 in their study including 75 healthy children. Falavarjani et al.13 showed that 15 children born preterm had a smaller or no foveal avascular zone when compared with normal children.

We investigated the size of the foveal avascular zone and the vessel density at the level of the superficial capillary plexus and deep capillary plexus in amblyopic children and normal children to determine whether there is a difference. We found the mean size of the foveal avascular zone was 0.291 mm2 in normal children and 0.261 mm2 in amblyopic children. This findings were similar to other investigators' findings in children.

Two reports were conducted in amblyopic children in the literature. Yilmaz et al.6 found that superficial capillary plexus and deep capillary plexus values were significantly lower in amblyopic eyes than in fellow eyes and controls. Lonngi et al.7 demonstrated a statistically significant lower vessel density in both the superficial capillary plexus and deep capillary plexus in 6 × 6 mm scans that were not found in 3 × 3 mm scans. No difference was reported with regard to foveal avascular zone in both studies. Similarly, we did not find any difference in foveal avascular zone measurement among groups. Unlike other studies, our results showed that there was no difference in retinal capillary plexus densities. Lonngi et al.7 had a wide range of refractive errors (−14.00 to +13.50 D) and ethnically diverse cases in their study that could have affected their results. Yilmaz et al.6 used a 6 × 6 mm area for macular scans that might reduce density and resolution because of the large field. We preferred to use a 3 × 3 mm area and we had a more homogeneous group with regard to refractive errors and ethnicity. Those might be reasons why our results were different from the other studies.

Our results indicate that amblyopic eyes and normal eyes have similar retinal capillary plexus densities and foveal avascular zone. Small subgroup analysis showed there was no difference between amblyopic eyes and fellow eyes. Based on our results, we hypothesize that the amblyopic process does not involve retinal microvasculature because animal models could not detect such evidence.14,15 Different levels of the visual pathways might or might not be affected in amblyopia. Also, these alterations might be structural or functional. Studies including histological sections are required to respond to these questions.

This study is limited by the relatively small sample size. It is unclear whether our findings would be generalizable to a larger group of patients. However, it is novel that amblyopic eyes and control eyes have analogous retinal microvasculature. Further studies using a larger sample size will clarify our findings.

References

  1. Von Noorden GK. Amblyopia: a multidisciplinary approach. Proctor lecture. Invest Ophthalmol Vis Sci. 1985;26:1704–1716.
  2. Kara O, Altintas O, Karaman S, Emre E, Caglar Y. Analysis of choroidal thickness using spectral-domain OCT in children with unilateral amblyopia. J Pediatr Ophthalmol Strabismus. 2015;52:159–166. doi:10.3928/01913913-20150311-11 [CrossRef]
  3. Kasem MA, Badawi AE. Changes in macular parameters in different types of amblyopia: optical coherence tomography study. Clin Ophthalmol. 2017;11:1407–1416. doi:10.2147/OPTH.S143223 [CrossRef]
  4. Tan CS, Lim LW, Chow VS, et al. Optical coherence tomography angiography evaluation of the parafoveal vasculature and its relationship with ocular factors. Invest Ophthalmol Vis Sci. 2016;57:224–234. doi:10.1167/iovs.15-18869 [CrossRef]
  5. Jia YL, Tan O, Tokayer J, et al. Split spectrum amplitude decor-relation angiography with optical coherence tomography. Opt Express. 2012;20:4710–4725. doi:10.1364/OE.20.004710 [CrossRef]
  6. Yilmaz I, Ocak OB, Yilmaz BS, Inal A, Gokyigit B, Taskapili M. Comparison of quantitative measurement of foveal avascular zone and macular vessel density in eyes of children with amblyopia and healthy controls: an optical coherence tomography angiography study. J AAPOS. 2017;21224–228.
  7. Lonngi M, Velez FG, Tsui I, et al. Spectral-domain optical coherence tomographic angiography in children with amblyopia. JAMA Ophthalmol. 2017;135:1086–1091. doi:10.1001/jamaophthalmol.2017.3423 [CrossRef]
  8. You Q, Freeman WR, Weinreb RN, et al. Reproducibility of vessel density measurement with optical coherence tomography angiography in eyes with and without retinopathy. Retina. 2017;37:1475–1482. doi:10.1097/IAE.0000000000001407 [CrossRef]
  9. La Spina C, Carvali A, Marchese A, Querques G, Bandello F. Reproducibility and reliability of optical coherence tomography angiography for foveal avascular zone evaluation and measurement in different settings. Retina. 2017;37:1636–1641. doi:10.1097/IAE.0000000000001426 [CrossRef]
  10. Mastropasqua R, Toto L, Mattei PA, et al. Reproducibility and reliability of foveal avascular zone area measurements using swept-source optical coherence tomography angiography in healthy subjects. Eur J Ophthalmol. 2017;27:336–341. doi:10.5301/ejo.5000858 [CrossRef]
  11. Golebiewska J, Olechowski A, Wysocka-Mincewicz M, et al. Optical coherence tomography angiography vessel density in children with type 1 diabetes. PloS One. 2017;12:e0186479. doi:10.1371/journal.pone.0186479 [CrossRef]
  12. Zhang Z, Huang X, Meng X, et al. In vivo assessment of macula in eyes of healthy children 8 to 16 years old using optical coherence tomography angiography. Sci Rep. 2017;7:8936. doi:10.1038/s41598-017-08174-9 [CrossRef]
  13. Falavarjani KG, Iafe NA, Velez FG, et al. Optical coherence tomography angiography of the fovea in children born preterm. Retina. 2017;37:2289–2294. doi:10.1097/IAE.0000000000001471 [CrossRef]
  14. Cleland BG, Crewther SG, Crewther DP. The cat as a model for visual deprivation. Aust N Z J Ophthalmol. 1985;13:263–269. doi:10.1111/j.1442-9071.1985.tb00433.x [CrossRef]
  15. Crewther SG, Crewther DP, Cleland BG. Convergent strabismic amblyopia in cats. Exp Brain Res. 1985;60:1–9. doi:10.1007/BF00237012 [CrossRef]

Clinical Characteristics of the Study Participantsa

CharacteristicControl (n = 21)Amblyopia (n = 17)
Age (y)9.6 ± 2.9 (6 to 16)8.6 ± 2.5 (6 to 16)
Sex
  Male9 (42.8%)8 (47%)
  Female12 (57.2%)9 (53%)
Spherical equivalent (D)0.67 ± 1.30 (−2.00 to +3.50)3.34 ± 0.90 (−1.50 to +4.50)
Visual acuity (logMAR)00.32 ± 0.06 (0.2 to 0.6)

OCT Angiography Measurements

ParameterControl (n = 21)Amblyopia (n = 17)Pa
SCP to whole (%).352
  Mean ± SD48.4 ± 2.548.8 ± 3.7
  Median (range)48.9 (42.9 to 52.6)50.6 (39.1 to 53.1)
SCP to foveal (%).199
  Mean ± SD19.3 ± 5.423.8 ± 8.8
  Median (range)19.4 (6.9 to 27.5)20.8 (15.3 to 48.1)
SCP to parafoveal (%).820
  Mean ± SD51.3 ± 2.750.9 ± 4.6
  Median (range)51.4 (45.6 to 55.9)52.1 (41.3 to 55.7)
DCP to whole (%).064
  Mean ± SD54.4 ± 3.251.8 ± 4.3
  Median (range)54.2 (49 to 61)52.9 (42.9 to 58.5)
DCP to foveal (%).416
  Mean ± SD34.9 ± 7.437.6 ± 5.8
  Median (range)36.2 (17.1 to 45)36.8 (30.7 to 48.5)
DCP to parafoveal (%).279
  Mean ± SD56.8 ± 3.254.8 ± 4.2
  Median (range)56.2 (52.3 to 63.5)55.5 (47.7 to 61.7)
FAZ (mm2).238
  Mean ± SD0.29 ± 0.10.25 ± 0.1
  Median (range)0.3 (0.1 to 0.57)0.24 (0.1 to 0.38)
CFT (µm).931
  Mean ± SD244.8 ± 15250.6 ± 27.8
  Median (range)247 (218 to 268)244 (220 to 336)

OCT Angiography Measurements of Patients With Unilateral Amblyopia

ParameterAmblyopic Eyes (n = 11)Fellow Eyes (n = 11)Pa
SCP whole (%).222
  Mean ± SD48.7 ± 4.547.1 ± 3.3
  Median (range)51.3 (39.1 to 53.1)47.2 (41.7 to 51.4)
SCP foveal (%).546
  Mean ± SD21.1 ± 5.821.06 ± 11
  Median (range)20.8 (15.3 to 34)17.8 (12 to 48.4)
SCP parafoveal (%).161
  Mean ± SD51.7 ± 4.749.7 ± 3.3
  Median (range)54.2 (41.3 to 55.7)49.5 (43.6 to 53.6)
DCP whole (%).161
  Mean ± SD53.9 ± 3.950.5 ± 4.04
  Median (range)55 (47.5 to 58.5)49.9 (44.7 to 59.2)
DCP foveal (%).340
  Mean ± SD38.2 ± 5.137.6 ± 8.6
  Median (range)37.2 (32.8 to 48.5)35.5 (30 to 57.9)
DCP parafoveal (%).136
  Mean ± SD56.3 ± 453.5 ± 3.9
  Median (range)57.4 (49.2 to 61.7)53.3 (48.5 to 61.6)
FAZ (mm2).370
  Mean ± SD0.26 ± 0.10.29 ± 0.04
  Median (range)0.26 (0.13 to 0.36)0.29 (0.23 to 0.34)
CFT (µm).863
  Mean ± SD243 ± 13.6244.4 ± 25.6
  Median (range)243 (225 to 271)241 (214 to 302)
Authors

From the Department of Ophthalmology, University of Health Sciences, Bakirköy Dr. Sadi Konuk Training and Research Hospital, Istanbul, Turkey.

The authors have no financial or proprietary interest in the materials presented herein.

The authors thank Prin Statistical Data Analysis Service for statistical analysis and Gokhan Demirayak for proofreading the article.

Correspondence: Bengi Demirayak, MD, FEBO, Department of Ophthalmology, University of Health Sciences, Bakirköy Dr. Sadi Konuk Training and Research Hospital, Istanbul, Turkey. E-mail: bengiyucel@hotmail.com

Received: May 31, 2018
Accepted: August 20, 2018
Posted Online: October 26, 2018

10.3928/01913913-20181003-02

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