We initiated this study in VKH patients who had been systemically treated with glucocorticoids and immunosuppressive agents but whose condition was poorly controlled. All patients had been treated for no less than 6 months. The medical records of VKH patients who were refractory to conventional therapy were collected and analyzed. This study was granted by the Zhongshan Ophthalmic Center Ethics Committee and conducted under the Declaration of Helsinki. The patients or their guardians were thoroughly informed of the potential hazards, and written informed consent was obtained before initiation of treatment.
Patients were eligible for inclusion if they met all of the following requirements: 1) they fulfilled the diagnostic criteria for VKH disease and received systemic medical glucocorticoids and immunosuppressive agents, but their condition was poorly controlled, with continuous degradation of visual function in the last 3 months and at least 2 relapses; 2) ocular inflammatory activity was present (anterior chamber cell grade or/and vitritis grade ≥ 1+ cells, optic nerve injury, vasculitis, retinitis or choroiditis); 3) patients had negative T-SPOT test results, or, in the event of a positive test, they had no signs of active tuberculosis and received precautionary anti-tuberculosis treatment.
Patients were excluded if: 1) presence of active systemic infections; 2) coexisting of contraindications to ADA, such as malignant diseases or tuberculosis; or 3) had received any surgeries that could improve visual acuity.
Treatment: ADA treatment was started with an induction dose of 80 mg subcutaneously, followed by 40 mg one week later and 40 mg every other week thereafter. Withdrawal of ADA or extension of the injection interval was based on stability of inflammation remission, patients’ wishes and other situations (such as inadequate response, intolerance, side effects or treatment costs). Glucocorticoids (given orally or intravenously) and immunosuppressants, such as methotrexate, cyclosporine A or mycophenolate mofetil, were prescribed depending on the previous medication and baseline severity of disease, and the doses of glucocorticoids and immunosuppressants were adjusted according to changes in diseases. Local treatments, such as intraocular anti-vascular endothelial growth factor treatment, glucocorticoid droplets, dexamethasone implants, and anti-glaucoma treatment, were provided according to the conditions.
The patient evaluations comprised a comprehensive physical examination, a thorough ophthalmic examination and laboratory blood tests (including routine bloodwork, liver and renal function tests, urinalysis, blood chemistry, the T-spot test, and other infectious disease tests). The primary outcomes included best corrected visual acuity (BCVA), intraocular inflammation, relapse and glucocorticoid sparing effects. Other outcomes included retinal morphology, intraocular manifestations and adverse events. All parameters were recorded at baseline and at every visit. All surgical information was recorded, especially for procedures that could improve visual function, such as cataract extraction.
Visual acuity: BCVA was evaluated by Snellen chart. In patients with exceptionally poor visual function of “counting fingers /hand motion /light perception”, BCVA was converted to a quantified visual acuity value for statistical convenience .
Intraocular inflammation: The recommendation of the Standardization of Uveitis Nomenclature Group in 1990 was used to assess anterior chamber inflammation, and the Nussenblatt scale was used to assess the vitritis grade [14, 15].
Relapse: A relapse was defined as the emergence or exacerbation of anterior chamber cells, vitritis, mutton-fat keratic precipitates or iris nodules.
Central macular thickness (CMT): CMT was defined as the average retinal thickness within a 1-mm-diameter region in the macular fovea.
Intraocular manifestations: These manifestations included new onset of complicated cataracts, serous retinal detachment (SRD), sunset glow fundus, Dalen-Fuchs nodules, iris nodules, mutton-fat KPs, iris neovascularization, pigmentation scatter, iris nodules (including Koeppe nodules and Busacca nodules), iris synechiae and any other associated complications.
Glucocorticoid-sparing effect: The glucocorticoid-sparing effect was defined as the reduction of glucocorticoid use at the final visit.
Adverse events (AEs): Patients were instructed to report any AEs during the treatment so that their regimen could be evaluated and adjusted. AEs were defined as activation of infections, allergic reactions and any other immunogenicity-related events.
For continuous parameters, the mean (SD) or median (interquartile range, or IQR) was used to describe the data. For categorical parameters, numbers or percentages were used. Student’s t-test was used to compare the BCVA and CMT before and after the treatment. The Wilcoxon test was used to compare pretreatment and posttreatment intraocular inflammation. SPSS ver.25.0 software was used for statistical analysis. P-value less than 0.05 was considered as statistically significant.