Analysis of Inner and Outer Retinal Thickness in Patients Using Hydroxychloroquine Prior to Development of Retinopathy

Abstract

IMPORTANCE Retinopathy is a known risk of long-term use of hydroxychloroquine sulfate. However, whether the inner as well as outer retina are involved before retinopathy develops and whether changes in the retina might signal impending toxic effects during screening remain unknown. OBJECTIVE To determine the degree of inner and outer retinal involvement in short-and long-term use of hydroxychloroquine before the development of retinopathy. DESIGN, SETTING, AND PARTICIPANTS This retrospective medical record review of spectral-domain optical coherence tomography (SD-OCT) findings was performed at an academic medical center. Thirty-two patients without retinopathy and with high-quality SD-OCT images were studied. Twenty-seven patients were age matched (49-65 years old) for comparison of retinal layers among patients who used the drug less than 5 years (n = 12) or longer than 15 years (n = 15) at the initial visit. Populations were also defined (without age limitation) for comparison of change during 25 to 52 months of follow-up among patients with initial use of less than 5 years (n = 7) or longer than 15 years (n = 8). Data were collected from 2010 to 2015. MAIN OUTCOMES AND MEASURES Measurements of inner and outer retinal thickness in SD-OCT images using commercial software and a Stanford pixel-by-pixel segmentation software that also provided topographic maps of thickness dimensions and change. RESULTS Thirty-two patients (5 men and 27 women) were included in the analysis. Measurements of inner retinal thickness between short-and long-term hydroxychloroquine users (n = 27) in different retinal regions, and during a median 39 months of follow-up (n = 15), showed no statistically significant differences or change. Similarly, no significant differences or changes were identified in outer retinal thickness except for the final visit of 1 patient who developed focal parafoveal thinning, a toxic effect of hydroxychloroquine use. Cirrus ganglion cell analysis measurements were inaccurate in the presence of outer retinal damage. CONCLUSIONS AND RELEVANCE The inner retina appears not to be involved in hydroxychloroquine-induced retinopathy to any clinically relevant degree within the limitations of our sample size. No clinically apparent warning of outer retinal damage was seen in the SD-OCT images of long-term hydroxychloroquine users until the actual appearance of focal retinopathy. Early detection of hydroxychloroquine-induced retinopathy is known to prevent visual acuity loss and serious progression after the therapy is stopped, and these data suggest that screening should seek distinct new areas of retinopathy (shown by topographic thickness maps) rather than long-term progressive thinning.

Structural and Functional Characterization of the Retinal Effects of Hydroxychloroquine Treatment in Healthy Eyes

“…Pasadhika and Fishman [19] also showed that a selective thinning of the inner retina can be quantified in the absence of any changes clinically visible in the fundus. Like almost all studies on the topic of hydroxychloroquine retinopathy [7, 15, 20-22], we are not able to draw any definite conclusion regarding the sequence of events associated with the disease, due to the retrospective cross-sectional design. However, our results also emphasize that the effects of long-term hydroxychloroquine are not limited to the outer retina.…”

“…Although with a sample size greater than the vast majority of studies with OCT data in hydroxychloroquine retinopathy [7-10, 13, 18, 22, 27, 28], we still recognize that stronger evidence could be derived from a larger cohort. We only included structural and functional characterization related to the central macular area, because there is a general consensus that the retinal effects of hydroxychloroquine are mainly targeted at the parafovea [1, 4].…”

“…This allowed us to have a consistent and thorough amount of raw data to objectively characterize, quantify, and locate the long-term effects of hydroxychloroquine. Another research group used a similar methodology but through a self-designed segmentation algorithm [7, 13]. Our approach, using the built-in software of a widely used commercial equipment, greatly favours replication of these results.…”

“…One group included patients under hydroxychloroquine treatment for less than 5 years, considered as “short-term” users. The same 5-year cut-off has been used in similar papers [7]. The remaining sample, under hydroxychloroquine treatment for a minimum of 5 years, was considered to represent the “long-term” effects of the drug.…”

Sicherheitsmanagement der Therapie mit Antimalariamitteln: was bedeuten die neuen Empfehlungen für die Praxis?

“…optische Kohärenztomografie (OCT) [13][14][15][16][17][18][19][20][21][22][23]. Die aGF sollte stan dardmäßig mit 10 Grad Durchmesser, 2 Grad Prüfabstand = 10-2 durchgeführt werden, bei asiatischen Patienten sind z.T.…”