Chloroquine (CQ), primarily used in the management of malaria and autoimmune diseases, has long been known to cause retinal toxicity. However, modern literature with multimodal fundus imaging findings remains limited. This retrospective study explores presumed CQ retinopathy cases at a tertiary US referral center with an emphasis on multimodal fundus imaging characteristics. This was a retrospective series of cases of presumed CQ toxicity seen at the Emory Eye Center between 2015 and 2022. Four men were identified with presumed CQ retinopathy, with a median age of 57 years (range 50-59 years). Chloroquine use occurred in malaria-endemic regions in each case, and the medication was self-administered in three cases. Optical coherence tomography consistently revealed outer band loss and varying degrees of foveal sparing. Fundus autofluorescence imaging demonstrated symmetric a bull's-eye pattern of autofluorescence abnormality with hyperautofluorescence along the rim of the diseased tissue. One case exhibited paravascular hyperautofluorescence in the setting of repeated intravenous CQ exposure. Multimodal retinal imaging revealed distinct yet diverse patterns of degeneration not readily visible on clinical examination. More generally, these findings raise public health concerns regarding self-administration of CQ in malaria-endemic regions.

Hydroxychloroquine (HCQ) is a cornerstone treatment for systemic lupus erythematosus (SLE). Despite its long-standing use, recent studies have refined recommendations on dosage, toxicity, adherence, and benefits. The 2023 EULAR and 2024 KDIGO guidelines recommend a dose of 5mg/kg/day, with adjustments for renal impairment. However, reducing HCQ dose to≤5mg/kg/day increases the risk of moderate-to-severe flares (OR=6.04 [1.71-21.3]) and lupus-related hospitalizations (aOR=4.2 [1.45-12.19]). The prevalence of HCQ-related retinopathy reaches 8.6-11.5% after 15 years of use. Established risk factors include high daily doses, prolonged treatment, renal impairment, tamoxifen use, and pre-existing maculopathy. Recent studies have identified additional risks, including female sex (HR=3.83 [95% CI, 1.86-7.89]), darker skin phototypes (OR=5.5 [1.4-26.5]), serotonin-norepinephrine reuptake inhibitors (OR=6.6 [1.2-40.9]), an [HCQ]/[DCQ] ratio<7.2 (OR=8.4 [2.7-30.8]), and antiphospholipid syndrome (OR=8.9 [2.2-41.4]). The 2024 PNDS recommends annual ophthalmologic screening after five years of treatment. HCQ withdrawal significantly increases relapse risk, with severe flares occurring up to six times more frequently. A study on patients discontinuing HCQ due to retinopathy found a higher relapse rate compared to adherent patients (31.3 vs. 12.5%, OR=3.1 [1.2-8.2]). An algorithm for interpreting HCQ blood levels has been proposed, identifying levels below 200ng/mL as markers of poor adherence, correlating with an 80% missed-dose rate. Moreover, several studies confirm that HCQ is safe during pregnancy and does not increase the risk of congenital malformations. Finally, HCQ has been associated with a reduced risk of cardiovascular events in SLE. A study involving 52,883 patients found that HCQ use significantly lowered the incidence of cardiovascular events (OR=0.63 [0.57-0.69]). Recent evidence reinforces HCQ's essential role in SLE. Careful dose management, adherence monitoring, and ophthalmologic screening are crucial for optimizing treatment outcomes.

The aim of this study was to present a patient with systemic lupus erythematosus on longstanding hydroxychloroquine (HCQ) use for whom HCQ was stopped because of signs of toxicity and then resumed four years later because of dire systemic need. This is a long-term retrospective study. Humphrey visual fields (10-2 and 24-2), fundus autofluorescence imaging, and spectral domain optical coherence tomography (OCT) were used to follow progression over time. The patient was on HCQ for 26 years, with a cumulative dose over 3,000 g. HCQ was stopped in 2011 because of macular toxicity. She remained off HCQ for four years, during which time she developed type 1 diabetes due to an immunologic attack on the pancreas and then JC (John Cunningham) viremia after a period of treatment with mycophenolate, which put her at risk for progressive multifocal leukoencephalopathy. Mycophenolate was discontinued, and HCQ was resumed with careful follow-up over the next 7 years. The toxic maculopathy showed only mild slow progression since HCQ was resumed. Careful annual monitoring using Humphrey visual field 10-2 and spectral domain OCT imaging remains the standard of care for the patients on HCQ. However, it may be possible with close monitoring when there is compelling systemic need to resume HCQ after it has been stopped, with only slow progression of the retinopathy. This allowed the patient to have an improved quality of life and reduced the risk of severe morbidity and mortality.

Hydroxychloroquine (HCQ) retinal toxicity is an important entity that can be challenging to differentiate from its mimickers. Bull's eye maculopathy is the classical presentation of HCQ retinopathy; however, its differential includes several drug-related retinal toxicities, inherited retinal disorders, and systemic conditions with associated retinopathies. Given the similarities in clinical presentation, imaging findings, and other diagnostic data, it can be quite challenging for all but the retina specialists to successfully identify retinal toxicity from HCQ. This review summarises HCQ retinopathy and its mimickers of with a special emphasis on key clinical and ancillary distinctions that can help comprehensive ophthalmologists and primary care offices in clenching this diagnosis.

Chloroquine and hydroxychloroquine, while effective in rheumatology, pose risks of retinal toxicity, necessitating regular screening to prevent visual disability. The gold standard for screening includes retinal imaging and automated perimetry, with multifocal electroretinography (mfERG) being a recognized but less accessible method. This study explores the efficacy of Artificial Intelligence (AI) algorithms for detecting retinal damage in patients undergoing (hydroxy-)chloroquine therapy. We analyze the mfERG data, comparing the performance of AI models that utilize raw mfERG time-series signals against models using conventional waveform parameters. Our classification models aimed to identify maculopathy, and regression models were developed to predict perimetric sensitivity. The findings reveal that while regression models were more adept at predicting non-disease-related variation, AI-based models, particularly those utilizing full mfERG traces, demonstrated superior predictive power for disease-related changes compared to linear models. This indicates a significant potential to improve diagnostic capabilities, although the unbalanced nature of the dataset may limit some applications.