This prospective, observational, comparative cross-sectional study was performed between July and September 2018 at Dr. Sadi Konuk Training and Research Hospital at the Health Sciences University in Bakırköy. Patients aged 20–76 who received a diagnosis of SS in the Rheumatology Department of this hospital were included in this study. The research protocols for this study were approved by the Ethics Committee of Dr. Sadi Konuk Research and Education Hospital and conducted in accordance with the tenets of the Declaration of Helsinki. Written informed consent was obtained from each participant or his/her guardian(s). The consent procedure was approved by the ethics committee. All patients fulfilled the 2013 American College of Rheumatology/ European League against Rheumatism (ACR/EULAR) criteria for SS. Whether the patients were active or in remission was determined by the Physician Global Assessment. SS was also classified as diffuse and limited, morphea, or linear based on clinical examination.
The age- and gender-matched control group consisted of healthy individuals with no history of ocular or systemic disease.
All participants underwent complete ophthalmologic examinations, including best corrected visual acuity (decimal fraction), intraocular pressure (IOP), slit-lamp examination of the anterior segment, and fundoscopic examination, conducted by the same clinician (FG). After the examination, the retinal nerve fiber layer (RNFL) and OCTA measurements were made using the RTVue device (RTVue-XR OCT; Optovue Inc., Fremont, CA, USA).
Finally, based on the files in the rheumatology clinic, the patients’ age, year of diagnosis, autoantibody profile [anti-nuclear antibody (ANA) titer, anti-centromere anticore, anti-Cenp, and anti-Scl 70 positivity], systemic corticosteroid, hydroxychloroquine, calcium canal blocker, immunosuppressive agent, corticosteroid (CS), aminosalicylic acid, anti-tumor necrosis factor usage status, and ocular symptoms were recorded.
The exclusion criteria included systemic conditions that affect optic disc perfusion, such as sine-scleroderma (involvement of visceral organs in the absence of skin involvement), scleroderma overlap syndrome (SS associated with features of other connective tissue erythematosus), diabetes mellitus, severe hypertension, and retinal diseases, as well as diseases that affect the optic disc, such as glaucoma, optic neuropathy, previous intraocular surgery or trauma, and evidence that could confound OCT interpretation, such as intraocular pressure > 21 mm Hg or oral CS use above 10 mm. Individuals with conditions that cause media opacity, such as corneal opacity, fatal dry eye syndrome, grade 3–4 nuclear cataracts, retinal microvascular abnormalities (e.g., generalized and focal arteriole narrowing, arteriovenous nicking that can interfere with hypertensive retinopathy), drusen, presence of chorioretinal scarring, and previous retinal vein occlusion, were also excluded from the study. Only images with a signal strength index > 8/10 were used for the analysis of vessel density.
OCT angiography was examined by the same person (FY) using the spectral domain OCT (RTVue-XR Avanti version 2018.0.0.14, Optovue, Fremont, CA, USA) in the morning (9:00–11:00am) to avoid possible diurnal variations. The volumetric scans were processed by the SSADA algorithm. One eye of each participant was examined and scanned during the same visit. The eye with higher image quality in OCTA measurement was included to the study.
All scans were made up of two 4.5 mm × 4.5 mm images of the optic disc area. RNFL thickness was averaged from a circular sampling profile with a diameter of 3.4 mm centered on the disc.
The peripapillary retinal area was defined as a 700-µm-wide elliptical annulus extending outward from the optic disc boundary (Fig. 1). The sectorial division of the peripapillary region was automatically performed by the OCTA device as superior and inferior hemi-radial peripapillary capillaries, and all quantitative results were recorded.
The peripapillary vessel density was defined as the proportion of the total scanned area occupied by blood vessels. These vessels were defined as pixels with decorrelation values over the threshold in the noise region, which were two standard deviations higher than the mean decorrelation value .
All measurements were performed using the manufacturer’s tools and Analytical AngioVue software.
Data analyses were performed using SPSS software (SPSS for Windows, v. 20.0; SPSS, Inc., Chicago, IL, USA). Descriptive statistics included the mean and standard deviation for normally distributed variables and the median for non-normally distributed variables. A p value of ≤ 0.05 was considered statistically significant. The Kruskal-Wallis test was performed to compare the differences between the two groups. A chi-square test was used to analyze the frequency data on gender. Spearman correlation analysis was performed to determine the relationships between the peripapillary perfusion parameters and related factors. An independent t-test was used for comparing the normally distributed independent variables, and the Mann-Whitney U test was used for the analysis of the independent variables that did not conform to a normal distribution. Regression analysis was performed for values with significant correlations.