Quantitative Fundus Autofluorescence in Systemic Chloroquine/Hydroxychloroquine Therapy

Abstract

To investigate the effect of systemic chloroquine/hydroxychloroquine (CQ/HCQ) on outer retinal health using quantitative fundus autofluorescence (QAF) imaging. Methods: For this prospective, cross-sectional study, 44 CQ/HCQ patients and 25 age-matched controls underwent multimodal retinal imaging including QAF (488 nm) and spectral-domain optical coherence tomography (SD-OCT) in addition to the recommended CQ/HCQ screening procedures. Custom written FIJI plugins enabled detailed QAF analysis and correlation with retinal thickness and comparison to the healthy controls. Results: Out of 44 patients, 29 (mean age 43.5 ± 12.2, range 22-59 years) exposed to CQ/HCQ (mean cumulative dose 724.2 ± 610.4 g, median 608.0 g, range 18.6-2171.0 g) met eligibility criteria. Four of these 29 patients had bull's-eye maculopathy (BEM). Mean QAF values were significantly higher in CQ/HCQ patients than in healthy controls. QAF increase started early after treatment onset, remained high even years after treatment cessation, and was not accompanied by pathologies in the other screening methods, including retinal thicknesses (except in BEM patients). Conclusions: QAF might be a useful tool in retinal imaging and in verifying systemic CQ/HCQ intake. The early onset and preserved high levels of QAF parallel findings of CQ deposition in the retina in animal models. Whether QAF can be used as a screening tool to detect early CQ/HCQ related maculopathy is the subject of long-term ongoing studies. Translation Relevance: Experimental QAF imaging in systemic CQ/HCQ therapy monitoring might be a useful tool to indicate the drug or its metabolites and to detect metabolic retinal changes.

Quantitative Fundus Autofluorescence in the Developing and Maturing Healthy Eye

“…In this context, we recently discussed the need for alternative QAF analysis patterns that enable a more detailed analysis and correlation with other imaging modalities or functional tests at distinct posterior pole regions 8 or pathologies. 12 Our functional (QAF)–structural (retinal thickness in SD-OCT) correlation revealed that in our young cohort, increasing QAF is related to a thickening of the RPE, which parallels findings from other studies. 13 In addition, in our study, diminished QAF intensities was found with thickening of the inner retina.…”

“…Since its release in 2011, 6 QAF values have then been reported for normal aging 7 and in several retinal diseases. 12 However, previous studies reported only one QAF value for each individual eye (QAF8, mean of QAF values from eight segments at the parafoveal region), with a risk of missing information for pathologic lesions from areas outside the QAF8 ring. Also, there were no appropriate patterns for structural and other functional tests that fit the QAF8 ring pattern, which complicates adequate structural-functional testing.…”

Frequency and risk factors for hydroxychloroquine retinopathy among patients with systemic lupus erythematosus

“…A well-known complication in long-term HCQ intake and high cumulative dose therapy is the development of a HCQ-related maculopathy, carrying the possibility of occurrence of irreversible sight-threatening bull’s-eye maculopathy (BEM). The primary site of toxicity in HCQ retinopathy is the photoreceptor layer with secondary degeneration of the retinal pigmented epithelium (RPE) [ 26 ].…”

Visual electrophysiology in the assessment of toxicity and deficiency states affecting the visual system

“…The exact mechanism of CQ and HCQ toxicity in the retina remains uncertain, though photoreceptors appear to be the primary target, with the retinal pigment epithelium showing damage at a later stage [ 6 ].…”

“…Early signs of CQ/HCQ toxicity include pericentral visual field defects with the Humphrey 10-2 protocol, perifoveal SD-OCT abnormalities (particularly disruption of the outer segment ellipsoid zone and loss of the external limiting membrane) [ 7 ]. Fundus Autofluorescence (FAF) changes (perifoveal hyper-autofluorescence with later mottled hyper- and hypo-autofluorescence) [ 6 ] and multifocal electroretinogram (mfERG) abnormalities. The mfERG is a cone-driven response recorded under light-adapted conditions from many areas of the retina simultaneously.…”