Evaluation of retinal microvasculature in exotropia with abnormal binocular vision by optical coherence tomography angiography

This retrospective study was conducted at the First Affiliated Hospital of Soochow University between October 2020 and November 2021. The study was approved by the Ethics Committee of the First Affiliated Hospital of Soochow University and adhered to the Declaration of Helsinki. Informed parental consent was obtained for all participants. Patients with concomitant exotropia of ≥ 45 prism diopters (PD) and over 6 years of age were included in the study. The binocular function was measured with the Synoptophore at three levels. The abnormal binocular function was defined as the absence of all grades. Those with high myopia (≤ -6.0 D), hyperopia, anisometropia (≤ -2.50 D), amblyopia, oblique muscle overaction, paralytic strabismus, restrictive strabismus, previous strabismus surgery, or organic eye disease were excluded. Controls were required to have normal binocular vision and a complete absence of any other type of strabismus. Patients with chronic systemic diseases and neurological disorders were also excluded. In total, 50 patients and 26 controls were recruited finally. We compared the difference between the exotropia and the control group. We also made a comparison between the dominant eye and the deviated eye in the exotropia group. The deviated eye was identified as the eye that was always fixated. We chose the right eye of the control group as the dominant eye. All patients underwent a complete ophthalmic examination, including best-corrected visual acuity (BCVA), refraction (Topcon; Tokyo, Japan), prism alternating cover test with accommodative targets for fixation (6 m), ocular motility tests, slit-lamp, posterior segment examination, axial length (IOL Master 700; Carl Zeiss Meditec AG, Jena, Germany) and OCTA. The ability to control exotropia was assessed using the Newcastle Control Score (NCS). Those with a high (poor) NCS (⩾ 4) were identified [17]. Ocular deviations in patients with concomitant exotropia were measured after 45 min of patch application. Refractive errors were analyzed as spherical equivalent values.

All participants underwent OCTA imaging with an undilated pupil. The OCTA images were acquired using a spectral-domain device with software (RTVue-XR Avanti with AngioVue software, OptoVue, Inc., Fremont, CA, USA). A 6*6-mm macular scan was performed on each patient. Split-spectrum amplitude-decorrelation angiography was used to examine the OCTA information. Each scan was automatically segmented to visualize the retinal thickness (RT), SCP, DCP of the retina, and FAZ using AngioVue [18]. The representative fundus photographs, OCT, and OCTA images from the deviated eyes and the dominant eyes are shown in Fig. 1.

The middle and outer rings centered on the fovea were divided into four quadrants: superior, nasal, inferior, and temporal. The SCP and DCP vessel density of each region was calculated from the binarised image, using the Otsu method [19], as the percentage of the area defined as the perfusion area [10] over the total area. The SCP en face images were segmented, with an inner boundary below the internal limiting membrane and an outer boundary at 9 μm above the inner plexiform layer. The DCP en face images were segmented with an inner boundary 9 μm above the inner plexiform layer and an outer boundary 15 μm below the outer plexiform layer. FAZ parameters were measured in the 1*1-mm scan. Images with the signal strength of less than 7, or unclear boundaries were excluded. All spectral-domain OCT examinations were performed by a single experienced technician. The technician was blinded to the baseline information of the patients. The OCTA images were included in the hospital’s medical records.

To the best of our knowledge, this was the first study to investigate RT and macular microvasculature in patients with large-angle deviation whose binocular vision was abnormal in comparison with healthy controls based on OCTA. In addition, we analysed nine zones of macular values from the perspective of the deviated eye and the dominant eye. More importantly, we investigated the difference between the deviated eye and the contralateral eye in large-angle exotropia to explore the retinal morphological alternation and the possible pathogenesis of strabismus. In addition, we set a more stringent p-value of less than 0.01 to reduce the bias of comparisons.

It should be noted that our study had some limitations. First and foremost, a relevant small sample size was included in the analysis, which may introduce a little bias. The comparisons for various metrics inevitably caused statistical error. Therefore, we established standard inclusion and exclusion criteria to avoid possible errors, such as excluding those with poor control (NCS ≥ 4) and considering a significant p-value less than 0.01. Then, all subjects had a large exodeviation and required strabismus surgery, whether the remaining binocular vision alters the results is still unclear. In addition, patients with concomitant strabismus may not be attentive to the blue spot in OCTA imaging. Due to the limited economic condition of the hospital, we could not provide an ultra-widefield fluorescein angiography image. The 6*6-mm scan of the macular area may also be sufficient for basic identification. This may be one of the reasons for data bias. Further studies with a larger sample size are needed, including the evaluation of the macular vasculature and binocular vision to provide identical guidance for clinical diagnosis.