Bull's Eye Maculopathy Research Articles

Bull's eye maculopathy

Bull's eye maculopathy

Hunter Syndrome and Bull's Eye Maculopathy.

Hunter Syndrome and Bull's Eye Maculopathy.

Natural history and biomarkers of KCNV2-associated retinopathy.

KCNV2-associated retinopathy is an autosomal recessive inherited retinal disease classically named cone dystrophy with supernormal rod response (CDSRR). This study aims to identify the best biomarker for evaluating the condition. A retrospective review of eight patients from seven families with genetically confirmed KCNV2-associated retinopathy was performed. The best corrected visual acuity (BCVA), full-field electroretinogram (ffERG), pattern ERG (pERG), fundus imaging: retinal photograph and fundus autofluorescence (FAF), and optical coherence tomography (OCT) were analysed. There was a disproportionate increase in b-wave amplitude with a relatively small light intensity increase, especially between the two dimmest stimuli of DA 0.002 and 0.01 (-2.7 and -2.0 log cd.s/m2). The a-wave amplitude was normal. The a-wave peak time was delayed in all stimuli. The b-wave peak time was delayed compared to normal, but the gap tightened as intensity increased. The b:a wave ratio was above or at the upper limit for the reference values. FAF bull's eye maculopathy pattern was prominent and variable foveal disruption on OCT was apparent in all patients. Legal blindness was reached before the age of 25. We identified three potential electrophysiology biomarkers to assist in evaluating future therapies: the disproportionate b-wave amplitude jump, delayed a-wave and b-wave peak time, and the higher than normal b:a wave ratio. Any of these biomarkers found with photoreceptor ellipsoid zone foveal-perifoveal disruption should prompt consideration for KCNV2 retinopathy. The BCVA natural history data suggests the probable optimum therapeutic window in the first three decades of life.

The Peripapillary Retina - A Common Juncture in Stargardt Disease and Idiopathic Intracranial Hypertension.

To present the multimodal imaging and functional exam findings in a case of combined Stargardt disease and idiopathic intracranial hypertension. The patient was evaluated with multimodal imaging including color fundus photography, short wavelength autofluorescence, spectral domain optical coherence tomography as well as functional testing such as Humphrey visual fields and full-field electroretinogram. A 35-year-old woman was referred for evaluation of bilateral transient visual obscurations over the course of 2 months. Optic disc edema was observed in both eyes as well as a bulls-eye maculopathy with pisciform flecks. Magnetic resonance imaging and subsequent lumbar puncture confirmed a diagnosis of idiopathic intracranial hypertension. Fundus autofluorescence demonstrated hyperautofluorescent flecks surrounding both the macula and the disc. Genetic testing and full-field electroretinogram confirmed a diagnosis of Stargardt disease. Notably, the peripapillary retina was not spared as is frequently seen in Stargardt disease, possibly due to the impact of disc edema in the area. The patient was treated with increasing doses of acetazolamide and familial testing for Stargardt disease was recommended. Both Stargardt disease and idiopathic intracranial hypertension are separately rare diseases with common anatomic intersection at the peripapillary retina. Stargardt disease typically spares the peripapillary retina; however, in the present case shows some evidence of peripapillary involvement. This finding suggests some relationship between disc edema due to idiopathic intracranial hypertension and the natural history of Stargardt disease.

Target in Sight: A Comprehensive Review of Hydroxychloroquine-Induced Bull's Eye Maculopathy.

We review the latest screening and diagnostic techniques, and the most recent recommendations on the management of hydroxychloroquine retinopathy. Hydroxychloroquine (HCQ) has been shown to cause retinal toxicity in a dose-dependent fashion. Early diagnosis is critical as the resultant retinopathy is not reversible. New imaging modalities, such as adaptive optics (AO), microperimetry, and retro-mode imaging, may show promise in the timely diagnosis of HCQ retinopathy. Automated visual fields and spectral-domain optical coherence tomography (SD-OCT) are the primary tests used in routine screening for HCQ retinopathy, but fundus autofluorescence (FAF) and multifocal electroretinogram (mfERG) have also been shown to be useful. A baseline ophthalmologic examination is recommended in all patients beginning long-term hydroxychloroquine therapy within the first year of starting therapy. Automated visual fields and SD-OCT should be included during this baseline exam in patients with pre-existing macular conditions. Afterwards, annual screening can be deferred for the first 5 years of HCQ treatment unless the patient has a major risk factor.

MACULAR ATROPHY AND PHENOTYPIC VARIABILITY IN AUTOSOMAL DOMINANT STARGARDT-LIKE MACULAR DYSTROPHY DUE TO PROM1 MUTATION.

To describe the phenotypic variability and rates of progression of atrophy in patients with PROM1 -associated macular dystrophy. Patients in this retrospective, longitudinal case series from a tertiary center had clinical examination and multimodal imaging performed. Areas of retinal pigment epithelium and ellipsoid zone loss over time by optical coherence tomography were calculated by two independent graders. Fifteen patients from five kindreds with an Arg373Cys mutation in PROM1 were studied. The average age was 39 years, and 80% were women. The visual acuity was 20/40 at presentation and 20/57 at last follow-up (average 4.8 years). Three distinct macular phenotypes were observed: 1) central geographic atrophy (13%), 2) multifocal geographic atrophy (20%), and 3) bull's eye maculopathy (67%). The overall rate of atrophy progression was 0.36 mm 2 /year, but the average rate of atrophy progression varied by macular phenotype: 1.08 mm 2 /year for central geographic atrophy, 0.53 mm 2 /year for multifocal geographic atrophy, and 0.23 mm 2 /year for bull's eye maculopathy. Patients with PROM1 -associated macular dystrophy demonstrate distinct phenotypes, with bull's eye maculopathy being the most common. The average rate of atrophy progression may be similar to reported rates for ABCA4 -related Stargardt disease and less than age-related macular degeneration. These results provide important measures for following treatment response in future gene and stem cell-based therapies.

Low ceruloplasmin levels exacerbate retinal degeneration in a hereditary hemochromatosis model.

In a previous report, a 39-year-old patient with high serum iron levels from hereditary hemochromatosis (HH) was diagnosed with a form of retinal degeneration called bull's eye maculopathy. This is atypical for patients with HH, so it was theorized that the low serum levels of ferroxidase ceruloplasmin (CP) of this patient coupled with the high iron levels led to the retinal degeneration. CP, by oxidizing iron from its ferrous to ferric form, helps prevent the oxidative damage caused by ferrous iron. To test this, a hepcidin knockout (KO) mouse model of HH was combined with Cp KO to test whether the combination would lead to more severe retinal degeneration. Monthly in vivo retinal images were acquired and, after 11 months, mice were euthanized for further analyses. Both heterozygous and homozygous Cp KO increased the rate and severity of retinal degeneration. These results demonstrate the protective role of CP, which is most likely owing to its ferroxidase activity. The findings suggest that CP levels may influence the severity of retinal degeneration, especially in individuals with high serum iron.

Presumed Unindicated Implantation of Posterior Chamber Phakic Intraocular Lens.

BACKGROUND Refractive surgery is one of the most frequently performed ocular surgeries worldwide. Implantation of the posterior chamber phakic intraocular lens has advantages over laser vision correction, especially in high refractive error cases. We present a case of a young adult women with poor vision who underwent bilateral posterior chamber phakic intraocular lens explantation due to high vault, shallow anterior chambers, and a picture of cone-rod dystrophy. CASE REPORT A 23-year-old woman was referred for poor vision following an implantation of bilateral toric implantable collamer lens (ICL) implantation when she was 18 years old for high myopic astigmatism and anisometropia. On presentation, the best corrected visual acuity was 4-6/200 and 2-3/200 in the right eye and left eye, respectively. Slit lamp examination indicated a clear cornea with pigment deposition on the endothelium, high ICL vault, shallow anterior chamber, and bowing of the iris bilaterally. The patient underwent bilateral removal of the ICLs on separate visits, yet the vision remained unchanged. Diagnostics revealed that the patient had bull's eye maculopathy with atrophy due to her cone-rod dystrophy, which caused the poor vision. CONCLUSIONS This report emphasizes the need for careful and appropriate patient and intraocular size selection for refractive surgery. It indicates the importance of thorough medical examination, including genetic testing, fundus examination, and optical coherence tomography when retinal dystrophy is suspected. Generally, close follow-up is crucial in the setting of high vaulting following ICL implantation to prevent secondary complications.

Medications Damaging Retinal Pigment Epithelium and Photoreceptor Complex-3: Pathogenesis, Diagnosis and Treatment (Clofazimine, Deferoxamine, Vitamin A Deficiency and Celiac Disease, Digoxin)

Toxic retinopathies are a variety of conditions resulting from retinal damage caused by systemically administered drugs. Although relatively rare, these conditions should be considered, especially when features of unusual retinopathy or maculopathy such as bilateral pigmentary disorder or retinal crystal deposition are present. It has been observed that some drugs damage the RPE and photoreceptor layer. Of these drugs, clofazimine; can be used in the treatment of tuberculosis, leprosy, and various cutaneous diseases, but it can cause color vision defects and bulls-eye maculopathy in a dose-dependent manner. Lesions detectable by various imaging methods have been described as associated with the use of deferoxamine mesylate, which is used as an iron-chelating agent. In vitamin A deficiency characterized by xerophthalmia symptoms, drusenoid deposits have been observed in the photoreceptor outer segment, in which rod function defects are prominent. In the use of digoxin, which has a very narrow therapeutic range, photoreceptor dysfunctions, which are manifested by deterioration in color perception, may develop. Most ocular side effects associated with systemic drug use are reversible after discontinuation of therapy if detected early. However, toxic effects can progress if undetected and cause retinal dysfunction associated with potentially irreversible vision loss.

Application of multicolour reflectance imaging for the characterisation of inherited retinal disorders.

To describe the role of multicolour reflectance images (MCI) in the phenotypic diagnosis of inherited retinal disorders (IRDs). A retrospective review of consecutive patients affected by IRDs examined with MCI techniques from January to December 2019 at a tertiary care referral centre. All patients had MCI, fundus autofluorescence and optical coherence tomography taken at the same time point. The ability of each modality to highlight clinical features was assessed. Lesions' size was also measured and compared among imaging modalities. Thirty eyes of 15 patients were included in the study, 6 males and 9 females, with a mean age of 44 years (range: 19-57.5). The most frequent clinical diagnosis were: pattern dystrophies, and late-onset retinal degeneration. Next-generation or Sanger sequencing analysis was carried out in all patients. Blue and green reflectance were relevant in highlighting peripheral mottling in fundus albipunctatus, pseudoreticular drusen in late-onset retinal degeneration, parafoveal hyperreflective area in bull's eye maculopathy and crystals in Bietti's crystalline dystrophy. Likewise, it is to mention the ability of infrared reflectance to detect hyperreflective patches in posterior pole in neurofibromatosis type 1 and retinal changes in pattern dystrophies and cone dystrophies. Multicolour imaging technique enables the detection of clinical features that could be overlooked by other imaging modalities, allowing accurate phenotypic characterisation of IRDs and guiding genetic diagnose, and may become a meaningful monitoring tool for future treatments.

Early onset monocular hydroxychloroquine maculopathy in a systemic lupus erythematosus patient with history of central retinal artery occlusion: a case report

BackgroundHydroxychloroquine is a widely used medication for various clinical conditions mainly rheumatological and dermatological autoimmune diseases e.g. systemic lupus erythematosus, rheumatoid arthritis and psoriasis. While it is considered a safe medication, it is well-established that it can cause retinal toxicity i.e. HCQ maculopathy. Guidelines for HCQ retinal toxicity screening include factors like body weight, daily dose, duration, systemic diseases and retinal diseases. In this case study, we report a specific association between CRAO as a retinal disease and early onset HCQ maculopathy in a SLE patient.Case presentationA 42-year-old Caucasian female SLE patient presented with a complaint of gradual progressive painless diminution of vision in the left eye that started 16 months earlier. Clinical evaluation of the patient revealed a history of sudden profound painless diminution of vision in the same eye 18 months earlier after which the patient experienced only partial improvement of vision. That episode of sudden diminution of vision was attributed to left CRAO, complicating SLE-related thrombophilia, confirmed by fundus fluorescein angiography. Based on that diagnosis, the patient had been prescribed HCQ. At the time of presentation, fundus examination revealed left bull's eye maculopathy and right normal fundus. Therefore, a diagnosis of HCQ maculopathy in the left eye was made after exclusion of other causes of unilateral bull's eye maculopathy.ConclusionOur case study is the first to report an association between CRAO as a specific retinal disease and early onset of HCQ maculopathy in a SLE patient. The unilateral bull's eye presentation which occurred in the eye with CRAO after only 16 months of HCQ treatment highly suggests that CRAO is probably the cause of such unusually early maculopathy. This case report highlights the importance of retinal diseases as risk factors for HCQ maculopathy. It also points out the lack of specific evidence concerning the association between specific retinal diseases and HCQ maculopathy.

Non-leaking cystoid macular edema and bull’s eye maculopathy caused by hydroxychloroquine toxicity in Asian patients

Introduction: Hydroxychloroquine (HCQ) is used for treating systemic lupus erythematosus (SLE). It can cause irreversible toxic retinopathy, we discuss the outcome of HCQ retinopathy and emphasize the distinct toxicity pattern in Asian patients. Case Series: We report a retrospective case series of two systemic lupus erythematosus (SLE) patients who presented with HCQ toxicity. Both Asian SLE patients were treated with HCQ over five years with cumulative dose of >1000 g. Both had characteristic findings on spectral domain optical coherence tomography (SD-OCT) and fundus autofluorescence (FAF). First patient had non-leaking cystoid macula edema (CME) associated with HCQ retinopathy and second patient had bull’s eye maculopathy (BEM). They exhibited different outcome after drug cessation. There was no disease progression in former whereas latter lost her central vision over two years. Conclusion: Non-leaking CME is rare and can be a sequence of HCQ retinopathy. Bull’s eye maculopathy is another manifestation of severe HCQ toxicity. Toxic damage to retina is irreversible, and may progress even after the drug is stopped, so is crucial to discontinue once toxicity is detected. Patients on HCQ warrant annual screening with multimodal imaging. There are racial differences in HCQ toxicity, hence distinct screening tests should be performed in Asian population.

Clinical Characterization of Autosomal Dominant and Autosomal Recessive PROM1 Mutation With a Report of Novel Mutation.

This study aims to provide clinical characterization of PROM1 mutation with a report of novel mutation. This study is a retrospective case series of six patients from a single institution with multimodal imaging, electroretinography, and genetic testing. Six patients aged 12 to 47 years were identified. Patients with autosomal recessive (AR) variants showed more severe panretinal dystrophy with symmetrical macular involvement and peripheral retinal pigment epithelium atrophy. The autosomal dominant (AD) variants, on the other hand, showed milder macular involvement with bull's eye maculopathy phenotype with minimal peripheral involvement. Among patients with AR variants, a younger patient with aberrant splicing showed a milder phenotype compared with patients with a nonsense mutation and an additional ABCA4 mutation. The authors describe patients with PROM1 retinopathy inherited AD and AR inherited patterns. Novel mutations of c.1909C>T and c.2050C>T were identified, leading to truncation of the protein at sequence p.Gln637* and p.Arg684*, respectively. [Ophthalmic Surg Lasers Imaging Retina 2022;53:422-428.].

Hydroxychloroquine Causes Early Inner Retinal Toxicity and Affects Autophagosome-Lysosomal Pathway and Sphingolipid Metabolism in the Retina.

Hydroxychloroquine (HCQ) is an anti-malarial drug but also widely used to treat autoimmune diseases like arthritis and lupus. Although there have been multiple reports of the adverse effect of prolonged HCQ usage on the outer retina, leading to bull's-eye maculopathy, the effect of HCQ toxicity on the inner retina as well as on overall visual functions has not been explored in detail. Furthermore, lack of an established animal model of HCQ toxicity hinders our understanding of the underlying molecular mechanisms. Here, using a small clinical study, we confirmed the effect of HCQ toxicity on the inner retina, in particular the reduction in central inner retinal thickness, and established a mouse model of chronic HCQ toxicity that recapitulates the effects observed in human retina. Using the mouse model, we demonstrated that chronic HCQ toxicity results in loss of inner retinal neurons and retinal ganglion cells (RGC) and compromises visual functions. We further established that HCQ treatment prevents autophagosome-lysosome fusion and alters the sphingolipid homeostasis in mouse retina. Our results affirm the notion that HCQ treatment causes early damage to the inner retina and affects visual functions before leading to characteristic toxicity in the macular region of the outer retina, 'bull's-eye maculopathy.' We also provide insights into the underlying molecular mechanisms of HCQ retinal toxicity that may involve autophagy-lysosomal defects and alterations in sphingolipid metabolism.

Deleterious variants in CRLS1 lead to cardiolipin deficiency and cause an autosomal recessive multi-system mitochondrial disease.

Mitochondrial diseases are a group of inherited diseases with highly varied and complex clinical presentations. Here, we report four individuals, including two siblings, affected by a progressive mitochondrial encephalopathy with biallelic variants in the cardiolipin biosynthesis gene CRLS1. Three affected individuals had a similar infantile presentation comprising progressive encephalopathy, bull's eye maculopathy, auditory neuropathy, diabetes insipidus, autonomic instability, cardiac defects and early death. The fourth affected individual presented with chronic encephalopathy with neurodevelopmental regression, congenital nystagmus with decreased vision, sensorineural hearing loss, failure to thrive and acquired microcephaly. Using patient-derived fibroblasts, we characterized cardiolipin synthase 1 (CRLS1) dysfunction that impaired mitochondrial morphology and biogenesis, providing functional evidence that the CRLS1 variants cause mitochondrial disease. Lipid profiling in fibroblasts from two patients further confirmed the functional defect demonstrating reduced cardiolipin levels, altered acyl-chain composition and significantly increased levels of phosphatidylglycerol, the substrate of CRLS1. Proteomic profiling of patient cells and mouse Crls1 knockout cell lines identified both endoplasmic reticular and mitochondrial stress responses, and key features that distinguish between varying degrees of cardiolipin insufficiency. These findings support that deleterious variants in CRLS1 cause an autosomal recessive mitochondrial disease, presenting as a severe encephalopathy with multi-systemic involvement. Furthermore, we identify key signatures in cardiolipin and proteome profiles across various degrees of cardiolipin loss, facilitating the use of omics technologies to guide future diagnosis of mitochondrial diseases.

NPHP1 Full Deletion Causes Nephronophthisis and a Cone-Rod Dystrophy.

To describe in detail the structural and functional phenotype of a patient with cone-rod dystrophy associated with a full deletion of the NPHP1 gene. A 30-year-old male with history of end-stage renal disease (ESRD) presented with progressive vision loss in early adulthood prompting evaluation for retinal disease. Ophthalmic evaluation was performed including, kinetic fields, electroretinography (ERG), spectral domain optical coherence tomography (SD-OCT), fundus auto-fluorescence (FAF), wide-angle fluorescein angiography and near infrared imaging (NIR). Visual acuity was 20/60 in each eye. Fundus examination revealed a subtle bull's-eye maculopathy confirmed with fundus autofluorescence. SD-OCT demonstrated perifoveal loss of the outer retinal layers with structural preservation further peripherally. Testing of retinal function confirmed loss of cone greater than rod sensitivities in a manner that co-localized to structural findings. ERG revealed decreased photopic and scotopic responses. Genetic testing confirmed a homozygous whole gene deletion of the NPHP1 gene. NPHP1-associated retinal degeneration may present as a cone-rod dystrophy in addition to the previously reported rod-predominant phenotypes and can notably be associated with systemic abnormalities, including renal disease. Our work further expands upon the growing literature describing retinal disease associated with systemic ciliopathies.

POS1393 QUANTITATIVE AUTOFLUORESCENCE FINDINGS IN PATIENTS UNDERGOING HYDROXYCHLOROQUINE TREATMENT

Background:Hydroxychloroquine (HCQ) is a relatively safe and effective drug widely used as primary or adjunctive treatment for several rheumatological and dermatological disorders1. HCQ modulates immune response through several mechanisms and has a tropism for pigmented ocular tissues, particularly retinal pigment epithelium (RPE)2. Its accumulation within RPE cells can lead to sight threatening retinal toxicity, with bull’s eye maculopathy (BEM) representing its advanced phenotype. 3 Quantitative Auto-Fluorescence (qAF) is an imaging modality that allows the measurement of retinal auto-fluorescence following short-wavelength light (488nm) excitation of retinal fluorophores (lipofuscin). 4 Two recent studies have focused on qAF values in patients treated with HCQ 5,6. In both cases qAF was increased in eyes with BEM. Furthermore, Reichel et al.6 were able to detect increased values of qAF in patients without BEM as early as 6 months after the start of HCQ treatment using an experimental imaging analysis procedure.Objectives:To measure quantitative autofluorescence (qAF) in patients under treatment with hydroxychloroquine (HCQ) with no apparent signs of retinal toxicity and to compare it with that of untreated subjects.Methods:Consecutive patients at risk for the development of HCQ retinal toxicity (duration of treatment >5 years or daily HCQ dose >5 mg/kg of actual body weight (ABW) and/or renal insufficiency)7 but no alterations on Spectral Domain - Optical Coherence Tomography, Short-Wavelength Autofluorescence and 10-2 Visual Field examination were recruited. Healthy subject matched by age and sex were also enrolled in the study. All subjects underwent qAF measurements in one eye. Images were analyzed using the conventional qAF grid by Delori calculating the qAF of 8 sectors of the intermediate ring and the mean of those values (qAF8).Results:Thirty-nine patients treated with HCQ (38 females, mean age 52,1 ± 8,6 years) and 39 untreated subjects (38 females, mean age 51,2 ± 8,6 years). In both HCQ patients and untreated subjects, qAF8 was positively correlated with age (p=0.004) (Figure 1). Although HCQ patients showed a higher mean qAF8 compared to untreated subjects (294,7 ±65,3 vs 268,9 ± 57,5), the difference was not significant (p=0.068). HCQ patients showed significantly higher mean qAF values in the inferior-temporal, inferior and inferior-nasal sectors of the intermediate ring of qAF grid compared to untreated subjects (all p<0.05).Figure 1.Visual representation of a model predicting the standardized qAF values as influenced by age and HCQ daily dose/ABW, calculated for a treatment duration of 15 years.Conclusion:These results suggest a possible preclinical increase of qAF values in inferior parafoveal sectors probably induced by HCQ exposure. Further studies are required to improve our understanding of preclinical stages of HCQ retinopathy and the possible role of qAF in the HCQ toxicity screening.

5-Year Progressive Bull's Eye Maculopathy Despite Cessation of Hydroxychloroquine in Asian Systemic Lupus Erythematosus Lady

A 57-year-old systemic lupus erythematosus Chinese lady with maintenance hydroxychloroquine (HCQ) therapy of 200mg daily for 21years was weighed 61.5 kg-67.7 kg (mean 65.6 kg) throughout [1]. Regular ophthalmological tests in past decades first revealed subtle retinal pigment epithelium (RPE) changes, simulating early pericentral retinopathy pattern, on 2014’s fundus autofluorescence photos (Figure-1), and HCQ was immediately stopped [2,3]. Bull’s eye maculopathy was progressing inferiorly (Figure-2), to a combined parafoveal and pericentral retinopathy pattern (Figure-3), eventually generalized RPE atrophy (Figure-4) [3,4]. Safety HCQ dosage is 5mg/kg/day, yet retinal toxicity risk increases with consumption duration [1]. Maculopathy could progress after cessation of HCQ, given its long half-life of >1month [5].

Visual loss under chloroquine treatment-and not (only) due to bull's eye maculopathy!

Visual loss under chloroquine treatment-and not (only) due to bull's eye maculopathy!

Quantitative Fundus Autofluorescence in Systemic Chloroquine/Hydroxychloroquine Therapy.

PurposeTo investigate the effect of systemic chloroquine/hydroxychloroquine (CQ/HCQ) on outer retinal health using quantitative fundus autofluorescence (QAF) imaging.MethodsFor 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.ResultsOut 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).ConclusionsQAF 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 RelevanceExperimental 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.