Patients with treatment-naïve active non-infectious uveitis who were referred to Uveitis Clinic of Seoul National University Hospital during the period from June 2017 to March 2020 were enrolled in this retrospective, comparative study. When both eyes met the inclusion criteria, data were recorded for both. This study was approved by the Institutional Review Board of Seoul National University Hospital (IRB No. 2112-086-1285) and adhered to the Declaration of Helsinki. Informed consent was obtained from each patient. The exclusion criteria were as follows; infectious uveitis or posterior uveitis with retinochoroidal infiltrating lesion in the posterior pole; preexisting maculopathy including epiretinal membrane, macular degeneration or pathologic myopia; present or history of glaucoma or optic neuropathy; ONH drusen. Patients with a history of vitreoretinal surgery or retinal photocoagulation, and poor quality images on OCT (signal strength index lower than 5) were also excluded.

At baseline, a detailed demographic and medical history was collected, and all subjects underwent a thorough ophthalmic evaluation, including examination for Snellen visual acuity, anterior segment examination, dilated fundus examination, spectral domain OCT (Cirrus 5000, Carl Zeiss Meditec, Inc., Dublin, CA, USA), and FA (Heidelberg Engineering, Heidelberg, Germany). The causes of uveitis were investigated through a meticulous systemic review and laboratory tests. Patients were referred to internists if systemic diseases were suspected. Uveitic activities were identified and recorded according to the SUN working group guidelines by one uvea specialist (H.G.Y.) [11]. Uveitic activity was defined as “active” in the case of 1+ or more cells in the anterior chamber or anterior vitreous, or active involvement of the posterior segment, and as “minimally active” when there were only 0.5+ cells in the anterior chamber or anterior vitreous without any involvement of the posterior segment. OCT scans were reacquired after treatment when uveitic activity decreased equal to or less than “minimally active.”

Fluorescein angiograms were assessed for the presence of ODH according to the FA grading scheme proposed by the Angiography Scoring for Uveitis Working Group [12]. The integrated software (version 5.1; Carl Zeiss Meditec, Inc.) was used for OCT image analysis obtained from ‘macular and optic disc cube 200 × 200 scans’ and following parameters were measured: central subfield thickness (CSFT), peripapillary RNFL thickness, optic disc rim area and disc area. Mean thicknesses from automated analysis algorithm were used for analysis. Subclinical edema (macular and optic disc) was defined as a thickening of less than the 99th percentile compared to the normal control, and more than the 99th percentile was defined as clinically significant edema, as assessed by the standard distribution scale of the integrated software. Comparisons between baseline and post-treatment were performed for the subgroup with subclinical macular or optic disc edema subjects.

Snellen visual acuity were converted into logarithm of the minimum angle of resolution (logMAR) values. The main outcome variable was the frequency of ODH and OCT parameters including CSFT, peripapillary RNFL thickness, optic disc rim area and disc area. Secondary outcomes included visual acuity, causative diagnosis, anatomic classification of uveitis, time to uveitic activity equal to or less than “minimal,” and frequency of clinically significant macular and optic disc edema at baseline. Comparisons at baseline and after treatment were performed using the Wilcoxon signed-rank test or paired t-test following the Shapiro-Wilk normality test. Correlations between the visual acuity and OCT parameters were determined with Spearman’s rank correlation coefficient. The statistical analysis was performed using SPSS software version 22.0 (IBM Corp, Chicago, IL, USA). A p-value < 0.05 was considered statistically significant.