Evolution of retinal changes measured by optical coherence tomography in the assessment of hydroxychloroquine ocular safety in patients with systemic lupus erythematosus.

OBJECTIVE: The objective of this report is to analyse retinal changes over a five-year period, assessed by spectral domain-optical coherence tomography (SD-OCT), in patients from the Lupus-Cruces cohort treated with hydroxychloroquine (HCQ). METHODS: SD-OCT screening was performed annually between 2012 and 2017. Average macular thickness (AMT), ganglion cell layer thickness (GCLT) and qualitative data of retinal pigment epithelium (RPE) and external retina (ExtR) were collected prospectively. We compared data from 2012 (first) and 2017 (second) SD-OCT. RESULTS: We studied 110 patients and 195 eyes. No cases of HCQ toxicity were detected. At the time of the second SD-OCT, 99% patients had taken a daily dose of HCQ ≤5 mg/kg/day. The median time on HCQ was 133 months. The mean AMT and GCLT were significantly lower in both eyes at the second SD-OCT; however, all the differences were clinically insignificant at less than 1%. Qualitative analysis of RPE and ExtR showed no significant changes. Similar results were found among patients with risk factors for retinopathy. The comparison of patients with and without risk factors showed no differences. CONCLUSIONS: This study shows clinically irrelevant retinal changes in an SLE cohort on HCQ treatment over a five-year follow-up. Our findings support the safety of long-term HCQ at doses ≤5 mg/kg/day.

Study of Flare Assessment in Systemic Lupus Erythematosus Based on Paper Patients.

OBJECTIVE: To determine the level of agreement of disease flare severity (distinguishing severe, moderate, and mild flare and persistent disease activity) in a large paper-patient exercise involving 988 individual cases of systemic lupus erythematosus. METHODS: A total of 988 individual lupus case histories were assessed by 3 individual physicians. Complete agreement about the degree of flare (or persistent disease activity) was obtained in 451 cases (46%), and these provided the reference standard for the second part of the study. This component used 3 flare activity instruments (the British Isles Lupus Assessment Group [BILAG] 2004, Safety of Estrogens in Lupus Erythematosus National Assessment [SELENA] flare index [SFI] and the revised SELENA flare index [rSFI]). The 451 patient case histories were distributed to 18 pairs of physicians, carefully randomized in a manner designed to ensure a fair case mix and equal distribution of flare according to severity. RESULTS: The 3-physician assessment of flare matched the level of flare using the 3 indices, with 67% for BILAG 2004, 72% for SFI, and 70% for rSFI. The corresponding weighted kappa coefficients for each instrument were 0.82, 0.59, and 0.74, respectively. We undertook a detailed analysis of the discrepant cases and several factors emerged, including a tendency to score moderate flares as severe and persistent activity as flare, especially when the SFI and rSFI instruments were used. Overscoring was also driven by scoring treatment change as flare, even if there were no new or worsening clinical features. CONCLUSION: Given the complexity of assessing lupus flare, we were encouraged by the overall results reported. However, the problem of capturing lupus flare accurately is not completely solved.