Cumulative Dose Of Hydroxychloroquine Research Articles

Hydroxychloroquine-induced pigmentation in rheumatic diseases: prevalence, clinical features and influencing factors.

To describe the clinical features of Chinese patients with hydroxychloroquine (HCQ)-induced pigmentation and analyze the potential risk factors associated with HCQ-induced pigmentation. A cross-sectional study was conducted over a duration of 7 months, during which patients who had received HCQ treatment for >6 months were included. Data was collected through a structured questionnaire that encompassed demographic and geographic characteristics, information on HCQ and concomitant medication usage, sun exposure characteristics, and hyperpigmentation-related characteristics. Univariate and multivariate analyses were employed to calculate the statistical association between HCQ-induced pigmentation and multiple variables. Out of 316 patients, 83 (26.3%) patients presented hyperpigmentation during HCQ treatment. Hyperpigmentation presented after a median duration of HCQ treatment of 12 months (interquartile range, 6.0 months-30.0 months) with a median cumulative dose of 108 g of HCQ (interquartile range, 36-288 g). The most frequently affected sites of pigmentation were the face (60.2%), lower limbs (36.1%), and hands (20.5%). There was a linear decrease in the incidence of pigmentation with increasing daily sun exposure time (p= 0.030). In the multivariate analysis, variables (cumulative HCQ dose and daily sun exposure time) were included in the final models. The results revealed an independent correlation between HCQ-induced pigmentation and daily sun exposure exceeding 1 h (OR: 0.431; 95%CI: 0.208-0.892; p= 0.023). The occurrence of HCQ-induced pigmentation is not uncommon, with an incidence rate of 26.3%. Daily sun exposure time exhibited a protective effect against HCQ-induced pigmentation.

Effect of hydroxychloroquine blood concentration on the efficacy and ocular toxicity of systemic lupus erythematosus.

In the absence of evidence-based guidance on the impact of hydroxychloroquine (HCQ) blood concentration on efficacy and ocular toxicity in systemic lupus erythematosus (SLE), the clinical monitoring of HCQ blood concentration is not yet widely performed, which raised concerns about the necessity of conducting HCQ blood concentration monitoring. In this retrospective study, we consecutively enrolled 135 patients with SLE who received HCQ treatment for more than 6months from July 2022 to December 2022. Ocular toxicity was evaluated by collecting relevant retinal parameters using optical coherence tomography angiography (OCTA). Therapeutic efficacy was evaluated using the SLE disease activity index (SLEDAI) and relevant clinical parameters. HCQ blood concentration was determined by high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). Spearman correlation analysis revealed that the cumulative dose of HCQ was positively correlated with the foveal avascular zone (FAZ) perimeter and FAZ area (r = 0.734, P < 0.001; r = 0.784, P < 0.001). Meanwhile, the treatment duration of HCQ was positively correlated with FAZ perimeter and FAZ area (r = 0.761, P < 0.001; r = 0.882, P < 0.001). The univariate and multivariate logistic regression analyses indicated that HCQ blood concentration was associated with the disease activity of patients with SLE (odds ratio 0.994, 95% CI 0.990-0.999). HCQ blood concentration may be an important factor in assessing the therapeutic effectiveness of SLE patients. The HCQ-related ocular toxicity was a long-term effect related to long term exposure, rather than the blood concentration of HCQ at the time of testing. More importantly, when addressing HCQ-related ocular toxicity, it may be crucial to pay attention to the cumulative dose and treatment duration of HCQ.

MICROVASCULATURE ALTERATIONS OF PERIPAPILLARY RETINA AND MACULA IN SYSTEMIC LUPUS ERYTHEMATOSUS PATIENTS WITHOUT OCULAR INVOLVEMENT BY OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY.

To evaluate microvasculature alterations of the peripapillary retina and macula and to assess whether the changes can detect preclinical retinopathy in systemic lupus erythematosus patients. Cross-sectional study of 32 systemic lupus erythematosus patients without retinopathy and 22 normal controls. Optical coherence tomography angiography was used to measure the microvasculature of the peripapillary retina and macula. Vessel densities (VD, %) and fractal dimensions of superficial capillary plexus (SCP) and deep capillary plexus were calculated. Compared with controls, macular vessel densities of the whole image SCP (macular vessel density of SCP-wi) and macular vessel density of inferior SCP (macular vessel density of SCP-i) were significantly reduced in systemic lupus erythematosus patients ( P < 0.05). The peripapillary vessel densities (peripapillary vessel density [pVD]) of a 2.5-mm circle of SCP (pVD of SCP Φ2.5 ), pVD of SCP Φ3.5 , and pVD of inferior region of the inner circle of SCP (pVD of SCP-ii) were significantly reduced in patients treated with hydroxychloroquine >5 years. Macular vessel density of SCP-wi declined with age (β = -0.12; P < 0.01) and pVD of SCP-ii declined with hydroxychloroquine cumulative dose (β = -0.01; P < 0.01). Macular vessel density of SCP-i had the best discrimination power of 0.77 ( P < 0.01). Systemic lupus erythematosus patients without ocular involvement had microvasculature alterations that were particularly evident in the SCP. Peripapillary retina microvasculature may be reduced in patients with longer hydroxychloroquine treatment.

Factors affecting bone mineral density in children and adolescents with systemic lupus erythematosus.

Patients with juvenile-onset systemic lupus erythematosus (JSLE) are at a high risk of entering adulthood with disease-related morbidities like reduced bone mass and osteoporosis. This study aimed to evaluate the clinical characteristics of JSLE and to analyze the factors associated with low bone mineral density (BMD) in these patients. Children and adolescents diagnosed with JSLE at a single institution in Korea were included. Demographic, clinical, and laboratory data as well as details about the use of glucocorticoids (GCs) and disease-modifying antirheumatic drugs were collected. The lumbar spine (LS) BMD z-score was measured using dual energy x-ray absorptiometry, and lateral thoracolumbar spine radiographs were collected. A total of 29 patients with JSLE were included in this study. Of these patients, 7 had a BMD z-score of -2.0 or lower and were designated as the low BMD group. The differences in the clinical parameters and treatment variables between the low BMD and non-low BMD groups were compared. Higher cumulative GC dose, longer GC exposure, and higher cumulative hydroxychloroquine (HCQ) dose were all associated with low BMD; among them, the main factor was the duration of GC exposure. There was no significant correlation between BMD and clinical profile, disease activity, or bone-metabolism markers. The duration of GC exposure, cumulative GC dose, and cumulative HCQ dose were risk factors for low BMD in patients with JSLE, with the main factor being the duration of GC exposure. Thus, patients with JSLE should be routinely monitored for low BMD and potential fracture risks, and GC-sparing treatment regimens should be considered.

Evaluation of early retinal changes in patients on long-term hydroxychloroquine using optical coherence tomography angiography.

Connective tissue diseases (CTD), including systemic lupus erythematosus and rheumatoid arthritis (RA), have long been treated with hydroxychloroquine (HCQ). However, prolonged HCQ use poses a risk of adverse effects, particularly retinopathy. To detect early retinal changes assessed by optical coherence tomography angiography (OCTA) in CTD patients with long-term HCQ treatment and to explore the relationship between OCTA parameters and the concentrations of HCQ and its metabolites. A cross-sectional study conducted from March 2020 to October 2021 at the First Affiliated Hospital of Anhui Medical University. The area and perimeter of the foveal avascular zone (FAZ), the thickness of the fovea and parafovea, and the vascular density of the superficial capillary plexus (SCP) and deep capillary plexus (DCP) in each area of the macula were measured by OCTA in 43 CTD patients treated with HCQ for over 6 months. Meantime, blood concentrations of HCQ and its metabolites were determined by high-performance liquid chromatography-tandem mass spectrometry, and the clinical documents of all 43 involved patients were collected. There is no significant correlation between OCTA outcomes and the patient's age, disease duration, and weight-dependent dose. HCQ cumulative duration positively correlated with FAZ area and perimeter (r = 0.419, p = 0.005 and r = 0.407, p = 0.007, respectively) and negatively correlated with the foveal vessel density in DCP (r = -0.378, p = 0.012). HCQ cumulative dose had a positive correlation with FAZ area and perimeter (r = 0.445, p = 0.003 and r = 0.434, p = 0.004, respectively) and had a negative correlation with foveal vessel density in SCP and DCP (r = -0.383, p = 0.011 and r = -0.424, p = 0.005, respectively). OCTA outcomes did not correlate with HCQ and its metabolite concentrations. OCTA could be used to detect microvascular changes in the macula of CTD patients with long-term HCQ therapy. It was not found the concentrations of HCQ and its metabolites were associated with retinal vascular changes.

Accelerated hydroxychloroquine toxic retinopathy.

To report a case series of patients with retinal toxicity due to hydroxychloroquine (HCQ) within a short span of treatment. A retrospective review of case records of patients with accelerated HCQ toxicity within 1year of starting the treatment was done. Systemic co-morbidities, details of HCQ treatment, details of ocular examination, and results of multimodal investigations were noted. Nine patients (1 male, 8 females) with age ranging from 40 to 73years (mean 54.2 ± 13.4years) who showed accelerated HCQ toxicity were included. None had systemic conditions or drug history predisposing to early HCQ toxicity. The treatment duration ranged from 2 to 11months and the cumulative HCQ dose ranged from 18 to 120g (mean 45.0 ± 33.0g). The visual acuity was normal in 8 (88.9%) patients and retinal evaluation was normal in 4 (44.4%). Optical coherence tomography was abnormal in 4 (44.4%). Six (66.6%) cases had reduced sensitivity in the parafoveal point on visual field testing. All 9 cases had multifocal electroretinographic changes diagnostic of HCQ toxicity. The HCQ treatment was stopped in 8 and continued with reduced dose in 1 patient. The mean duration of follow-up was 11.2 ± 9.6months during which 5 patients showed improved mfERG and 1 patient had a stable mfERG. Visual fields improvement was noted in 2 cases. Patients on HCQ need to be kept on regular monitoring with more frequent follow-ups to detect signs of early onset toxicity and prevent permanent visual impairment. mfERG is an important diagnostic tool for HCQ toxicity.

Effects of hydroxychloroquine therapy on choroidal volume and choroidal vascularity index.

To determine changes in choroidal volume (CV) and choroidal vascularity index (CVI) in patients on hydroxychloroquine (HCQ) therapy. Retrospective analysis of patients on HCQ therapy. CV and CVI were assessed below the central foveal region on spectral-domain optical coherence tomography using an automatic denoising and localization algorithm. CV and CVI were compared with age-matched controls. Regression analyses were performed to generate associations between CV and CVI with demographics and HCQ treatment parameters. Associations were assessed using a generalized estimating equation model adjusted for intra-subject inter-eye correlations. A total of 137 adult patients (23 males and 114 females) were included. Mean age was 45.6 ± 13.7 years and most patients identified as Caucasian (79%). Total duration of HCQ therapy ranged from 3 months to 20 years. Daily HCQ intake varied from 150-600 mg (mean = 304 mg), while cumulative doses ranged from 18-2,800 g. At presentation, the median CV was 0.51 (IQR:0.356-0.747) mm, and median CVI was 0.559 (IQR:0.528-0.578). Increased cumulative HCQ dose was associated with decreased CV (p = 0.006). Compared to age-matched controls, CV, CVI, and luminal area were significantly lower in the study group (p = 0.0003, 0.0001, and 0.0002). In this study, we present a novel analysis of key biomarkers which predate the occurrence of HCQ retinopathy. Choroidal volume and vascularity index are significantly reduced in patients on HCQ therapy, especially at higher cumulative doses. These findings suggest new tools to guide medical decision-making for patients receiving HCQ therapy for rheumatologic diseases.

Evaluation of Retinal Toxicity by SD-OCT due to Long-Term Exposure to Hydroxycholorquine among Rheumatoid Arthritis Patients

Background Hydroxychloroquine is used increasingly in the management of a variety of autoimmune disorders, with well-established roles in dermatology and rheumatology and emerging roles in oncology. However, Hydroxychloroquine and chloroquine (CQ) have been associated with irreversible visual loss due to retinal toxicity. Cessation of the use of hydroxychloroquine at an early stage of damage might prevent functional loss; however, after maculopathy has developed, cessation of the drug does not show clinical recovery. Because discontinuation of Therapy may reverse retinal toxicity, early detection of toxicity changes is vitally important. Objective to evaluate the involvement of retina in hydroxychloroquine (HCQ) retinopathy among rheumatoid arthritis patients using data from spectral domain optical coherence tomography (SDOCT) and to correlate toxicity with dose, duration of use and cumulative effect of HCQ. Patients and Methods Cross sectional Study. In total 13 patients (26 eyes) attending the rheumatological outpatient clinic of El Demerdash hospital, from October 2019 to February 2020 were enrolled in the study after the approval of the research ethical committee in the Faculty of Medicine, Ain Shams University. A full history was taken from the patients and full ophthalmological examination was done. In our study we perform OCT for all patients by using the Nidek RS-3,000 Advance SD-OCT with the “Macula Map” protocol that imaged a 6 × 6 mm area with 64 raster B-scans, each composed of 1024 A-scans. Results The study showed that was highly significant negative correlation between duration of exposure and CMT (p-value =0.008) and highly significant negative correlation between cumulative dose and CMT (p-value =0.005). Also, there was statistically significant negative correlation between age and thickness of inner and outer nasal quadrant (p-value= 0.015, p-value= 0.001) respectively and between age and inner and outer superior quadrant (p-value= 0.048, p-value= 0.000) respectively, in ETDRS thickness map. It also found statistically significant negative correlation between daily dose and thickness of outer nasal quadrant of thickness map (p-value= 0.045). Conclusion The present study show the presence / absence of retinal toxicity in rheumatoid arthritis patients use hydroxychloroquine for 5years or more using SD-OCT and found a statistically significant negative correlation between central macular thickness and cumulative dose of HCQ and between central macular thickness and duration of HCQ use.

Analysis of choroidal thickness in juvenile systemic lupus erythematosus and its correlation with laboratory tests

BackgroundThe aim of this study is to investigate the alterations of choroidal thickness (CT) in juvenile systemic lupus erythematosus (JSLE) using enhanced depth imaging optical coherence tomography (EDI-OCT). We also aimed to assess whether CT parameters correlated with systemic health status in JSLE patients.MethodsJSLE patients and age- and sex-matched healthy subjects were recruited. A detailed ophthalmological examination was applied to all participants. CT measurements were acquired in the macular region using EDI-OCT. Moreover, a spectrum of laboratory tests was examined to evaluate the systemic conditions, and the Th1/Th2/Th17/Treg cytokine profiles in the peripheral blood were also analyzed in JSLE group.ResultsA total of 45 JSLE patients with no visual impairment and 50 healthy individuals were enrolled in the study. CT values in the macular region were decreased in JSLE patients when compared with healthy controls, even adjusting for age, axial length and refraction. There were no significant correlations between CT and cumulative dose of hydroxychloroquine or duration of hydroxychloroquine use (all P > 0.05). The average macular, temporal and subfoveal CT in JSLE group was negatively correlated with IL-6 and IL-10 (all P < 0.05), but had no significant correlations with other laboratory results (all P > 0.05).ConclusionsJSLE patients without ocular involvement may have significant variations in choroidal thickness at the macular area. Choroidal alterations might be associated with the systemic cytokine profiles in JSLE.

Evaluation of Changes in the Ganglionic Cell inner Plexiform Layer and Macular Retinal Nerve Fiber Layer in Patients Receiving Hydroxychloroquine

Backgrounds: To evaluate changes in the thickness of ganglion cell-inner plexiform layer and macular retinal nerve fiber layer using ocular coherence tomography in patients exposed to hydroxychloroquine .&#x0D; Methods: This was a retrospective, cross-sectional study of patients on hydroxychloroquine therapy. Ocular coherence tomography images showing ganglion cell-inner plexiform cell layer and macular retinal nerve fiber layer thickness were obtained and compared to controls. The relationship between the thickness of ganglion cell-inner plexiform and macular retinal nerve fiber layer, duration and cumulative dose of hydroxychloroquine were evaluated.&#x0D; Results: In all, 219 subjects were included. The Thickness of the ganglion cell-inner plexiform thickness was significantly less than controls (p = 0.006). The average macular RNFL thickness was less in the study compared to the control groups, but not statistically significant (p = 0.389). There was no significant correlation between ganglionic cell-inner plexiform and macular retinal nerve fiber layer with duration, daily dose, or cumulative dose of hydroxychloroquine.&#x0D; Conclusion: Thinning of the ganglionic cell- inner plexiform layer could be an early indicator of retinal toxicity before the appearance of clinical retinopathy.

Association between cumulative dose of hydroxychloroquine and electrocardiographic abnormalities in patients with systemic lupus erythematosus

ObjectiveHydroxychloroquine (HCQ) is one of the most used drugs in patients with systemic lupus erythematosus (SLE). In these patients, where heart involvement is common, cardiac HCQ toxicity may lead to fatal outcomes. The aim of this work is to study the influence of cumulative HCQ (cHCQ) in a selected group of patients with SLE and its association with electrocardiographic (EKG) abnormalities. MethodsSingle-center retrospective, observational study in which data were collected from the medical records of consecutive patients with a diagnosis of SLE who started treatment with HCQ and who had a 12-lead EKG before starting treatment and during follow-up. EKG abnormalities were grouped as conduction or structural abnormalities. The association of cHCQ with the occurrence of EKG disturbances was analyzed together with other demographic and clinical variables through univariate and multivariate logistic regression models. Results105 patients were selected with median cHCQ of 913 g. The sample was classified into two groups, above or below 913 g. Significantly, more conduction disturbances were observed in the group above the median (OR: 2.89; 95%CI: 1.01–8.23). In the multivariate analysis, the OR per 100 g of cHCQ dose was 1.06 (95%CI: 0.99–1.14). Age was the only variable associated with conduction disturbances. There were no significant differences in the development of structural abnormalities and a tendency for more high-grade atrioventricular block was shown. ConclusionOur study suggests an association between the cHCQ and the development of EKG conduction disturbances that disappears after multivariate adjustment. No increased number of structural abnormalities was observed.

Possible relationship between hydroxychloroquine and electrocardiographic and echocardiographic abnormalities in patients with inflammatory rheumatic diseases--a monocentric study.

Hydroxychloroquine (HCQ) is used in the treatment of inflammatory rheumatic diseases and is considered a safe drug. The role of HCQ in the COVID-19 pandemic highlighted some deleterious cardiac effects of HCQ. We aim to evaluate the prevalence and development of cardiac-adverse events in HCQ-treated patients with inflammatory rheumatic diseases. We performed a cross-sectional study where patients aged ≥18years with a diagnosis of inflammatory rheumatic disease currently exposed or not to hydroxychloroquine underwent electrocardiogram (ECG) and echocardiogram. Comparisons between groups were evaluated using chi-square, t test, and Mann-Whitney U test. Logistic regression was performed to determine predictors of changes in ECG and echocardiography. Eighty patients were included, 75 (93.8%) female, aged 52 ± 13years. ECG changes were seen in higher proportion in patients with hypertension (40.6% vs 12.5%, p = .004) and higher median potassium levels-4.5 (4.1-4.8) versus 4.2 (4.0-4.4), p = .023. Echocardiography changes were seen in older patients (59 ± 11 vs 50 ± 13years, p = .003) and in patients with higher cumulative dose-1752 (785-2190) versus 438 (328-1022) g, p = 0.008 - and time of exposure to HCQ - 12 (6-15) versus 4 (2-9) years, p = 0.028. HCQ cumulative dose (OR 1.001, CI95% 1.000-1.002, p = .033) and exposure time (OR 1.136, CI95% 1.000-1.289, p = .049) were predictors of echocardiography changes, but when adjusted for age, neither HCQ cumulative dose nor exposure time were predictors of echocardiography changes. No association was found between changes in ECG and echocardiogram in patients under HCQ, which remains a safe drug in patients with inflammatory rheumatic diseases.

Retinal microvascular density analysis in patients with rheumatoid arthritis treated with hydroxychloroquine

PurposeRheumatoid arthritis (RA) is the most common inflammatory joint disease, and hydroxychloroquine (HCQ) is an established treatment. The extent to which HCQ impacts ocular microvascular vessel density (VD) in patients with RA without evidence of HCQ retinopathy has not yet been conclusively clarified. The main aim of this study was to evaluate VD measured by optical coherence tomography angiography (OCTA) in patients with RA treated with HCQ.MethodsThe VD data of the 3 × 3 mm OCT angiogram (RTVue XR Avanti, Optovue Inc., Fremont, California, USA) as well as the retinal thickness (RT) data of patients with RA (n = 30) and healthy controls (n = 30) were extracted and analyzed. The study group was further divided into patients undergoing HCQ treatment for > 5 years (high-risk-group) and < 5 years (low-risk group).ResultsPatients with RA showed no evidence of VD reduction compared to the control group in all obtained regions (p > 0.05). Correlation analysis revealed no dependency between VD, RT, and HCQ therapy duration or cumulative HCQ dose (p > 0.05). High-risk patients showed a decreased VD in the superficial quadrant of the superficial capillary plexus compared to low-risk-patients (p = 0.022). Whole-en-face RT was reduced in the high-risk group compared to the control group (p = 0.019).ConclusionOur study showed no evidence that HCQ diminishes VD in patients with RA without HCQ retinopathy measured by OCTA. However, RA patients with a long duration of therapy showed a significantly reduced RT. Our results suggest that quantitative VD analysis by OCTA may not be suitable for early detection of HCQ retinopathy and that the focus on detecting early HCQ retinopathy should be on intensive and sequential OCT diagnostics.

Macular and peripapillary vessel density alterations in a large series of patients with systemic lupus erythematosus without ocular involvement

The aim of this study was to investigate changes in both macular and peripapillary retinal microcirculation in the subclinical period of systemic lupus erythematosus (SLE) patients and to assess the relationship of these changes with disease activity, damage index, renal involvement, and use of hydroxychloroquine (HCQ). Sixty eyes of 60 SLE patients and 60 age-matched, healthy controls were evaluated with optical coherence tomography angiography (OCTA). Vessel densities, structural parameters, and foveal avascular zone (FAZ) assesments were made. There was no significant correlation between activity and damage index and all regions of both superficial (SCP-VD) and deep capillary plexus vessel densities (DCP-VD) in the SLE group. There were no significant difference between groups in terms of FAZ, structural parameters, and radial peripapillary capillary vessel densities (RPC-VD). The mean SCP-VD and DCP-VD of most regions showed a significant decrease in the SLE group, except for parafovea superior and parafovea temporal. The decrease in vessel density (VD) in the perifoveal regions of DCP-VD in SLE patients was remarkable. DCP-VD showed good specifity and sensitivity in detecting vascular changes in SLE patients with whole image area under the curve (AUC) = 0.671, p < 0.001, odds ratio (OR) = 0.909, p = 0.009, and perifovea AUC = 0.671, p < 0.001, OR = 0.918, p = 0.012. Similarly, the SCP-VD whole image AUC = 0.609, p = 0.037, and OR = 0.825, p = 0.018 and perifovea AUC = 0.608, p = 0.037, and OR = 0.918, p = 0.012. The DCP-VD of perifovea superior showed a diagnostic accuracy for discrimination between SLE patients with and without nephritis (AUC = 0.671, p = 0.016). The SCP-VD and cumulative dose of HCQ demonstrated significant negative correlation in the SLE group (whole image, r = - 0.332, p = 0.010). SLE patients without ocular involvement had vascular changes that were particularly evident in the DCP and primarily in the perifovea. The perifovea superior of DCP had diagnostic utility in patients with nephropathy.

Machine Learning–Based Automated Detection of Hydroxychloroquine Toxicity and Prediction of Future Toxicity Using Higher-Order OCT Biomarkers

Despite guidelines for hydroxychloroquine (HCQ) toxicity screening, there are clear challenges to accurate detection and interpretation. In the current report, the feasibility of automated machine learning (ML)-based detection of HCQ retinopathy and prediction of progression to toxicity in eyes without preexisting toxicity has been described. Retrospective, longitudinal cohort study. Subjects on HCQ therapy. This was an institutional review board-approved, retrospective, longitudinal image analysis of 388 subjects on HCQ. Multilayer, compartmental, retinal segmentation with ellipsoid zone (EZ) mapping was used to harvest quantitative spectral-domain (SD)-OCT biomarkers. Using a combination of clinical features (i.e., cumulative HCQ dose and the duration of therapy) and quantitative imaging biomarkers (e.g., volumetric EZ integrity and compartmental measurements), ML models were created to detect toxicity and predict progression based on ground-truth OCT-based toxicity readings by 2 masked retina specialists. Furthermore, 10-fold cross-validation was performed. The model performance was visualized using receiver operator curves and calculating the area under the curve (AUC). The corresponding sensitivity and specificity values were evaluated for the feasibility of HCQ toxicity screening and prediction. The prevalence of HCQ toxicity in this cohort of 388 patients was 9.8% (n= 38). Twenty-one eyes progressed to toxicity during follow-up. OCT-based features (i.e., partial EZ attenuation, EZ volume, outer nuclear layer volume, and compartmental thicknesses) and clinical features (i.e., HCQ daily dose, HCQ cumulative dose, and duration of therapy) showed significant differences between the toxic and nontoxic groups. Percentage area with partial EZ attenuation (i.e., percentage of the macula with an EZ-retinal pigment epithelium thickness of ≤ 20 μm) was the most discriminating single feature (toxic, 35.7 ± 46.5%; nontoxic, 1.8 ± 4.4%; P < 0.0001). Using a random forest model, high-performance, automated toxicity detection was achieved, with a mean AUC of 0.97, sensitivity of 95%, and specificity of 91%. Furthermore, the toxicity progression prediction model had a mean AUC of 0.89, with a sensitivity and specificity of 90% and 80%, respectively. This report described the feasibility of high-performance automated classification models that used a combination of clinical and quantitative SD-OCT biomarkers to detect HCQ retinal toxicity and predict progression to toxicity in cases without toxicity. Future work is needed to validate these findings in an independent dataset.

Evaluation of Corneal and Retinal Toxicity in Rheumatoid Arthritis Patients Treated with Hydroxychloroquine

Introduction: The study aimed to assess the ocular toxicity of hydroxychloroquine (HCQ) by confocal microscopy, multifocal electroretinography (mfERG), and scanning laser polarimetry with variable corneal compensation (GDxVCC) in patients with rheumatoid arthritis (RA). Methods: A cross-sectional, comparative case series study was retrospectively conducted on 61 patients under HCQ treatment for RA without fundoscopic anomalies (group 1), 65 RA patients with no HCQ treatment (group 2), and 27 normal subjects (group 3). A comprehensive ophthalmological examination, including confocal microscopy, mfERG, and GDxVCC, was performed in the three groups. Results: In group 1, the duration of treatment ranged from 19 to 96 months (54.9 ± 15.2 months). The mean cumulative dose of HCQ was 446.1 ± 164.0 g (range 114–864 g). Confocal microscopy revealed hyper-reflective abnormal particles in 45 patients (73.8%) and beaded, tortuous fibers in 34 patients (55.7%) in group 1. No corneal change was observed in the other two groups. The mfERG responses in the 6 concentric rings (R1–R6) among the three groups differed except at R3 (all p < 0.05), and data from R1–R6 were not significantly different between groups 2 and 3. The retinal nerve fiber layer thicknesses were statistically thinner in group 1 than in groups 2 and 3 (all p < 0.05). Conclusions: Early signs of corneal and neural retina structure changes were detected in patients with RA treated with HCQ. Whether these findings should be a mark of drug recession still needs further study and more evidence.

Hydroxychloroquine's Early Impact on Cone Density.

Purpose To evaluate early effects of hydroxychloroquine (HCQ) on the retina using adaptive optics (AO). Methods This was a prospective observational single-center study of 29 eyes of 29 patients who had been treated with HCQ for the first time and followed with AO for a minimum of two years. Cone counting was performed in 4 quadrants, nasal, temporal, superior, and inferior, at 0.75 mm from the foveal center. The changes of cone density on AO, visual acuity, and foveal thickness within two years of use were analyzed. The changes of mean cone density of patients whose cumulative dose was over 200 g in 2 years were also assessed. We evaluated the correlation between cone density and cumulative dose of HCQ. Results There was no significant decrease in cone density in the first 2 years of HCQ use. VA and foveal thickness did not show obvious change, either. Among 9 patients whose cumulative dose was over 200 g in 2 years, the mean cone density showed no significant change at 6, 12, 18, and 24 months compared with baseline (P=0.381, P=0.380, P=0.281, and P=0.534, respectively). There was no correlation between cone density and cumulative dose of HCQ at two years (Spearman's correlation coefficient, r = −0.0553, P=0.780; n = 29). Conclusion AO showed no change in cone density in the first two years of HCQ use.

Prevalence of hydroxychloroquine retinopathy with long-term use in a cohort of Indian patients with rheumatic diseases

The study aims to estimate the prevalence of hydroxychloroquine (HCQ) retinopathy in a cohort of Indian patients and analyse the associated factors. Adult patients with rheumatological disorders aged ≥ 18years using HCQ for more than 5years and/or having received a cumulative dose > 400g were included. Demographic and clinical data were collected and all underwent ophthalmological tests which included Humphrey automated visual fields (AVF) and spectral domain optical coherence tomography (SD-OCT). The various clinical characteristics of the patients were compared. The study included 110 patients with a mean age of 43.5 ± 10.1years and predominantly females. Eleven patients (10%) were diagnosed with definite HCQ retinopathy. The mean daily dose of HCQ (mg/kg of real body weight) was significantly different in the groups with and without retinopathy (5.7 ± 0.9 vs 5.1 ± 0.8, p = 0.04). Patients with retinopathy had significantly more colour vision abnormalities (odds of 16.9; confidence interval 4.1-69.1, p = 0.0001) and higher prevalence of both parafoveal and perifoveal thinning (p < 0.0001). Age, gender, duration of HCQ use, cumulative HCQ dose and body mass index were not found to be associated with retinopathy. Four out of 11 patients had abnormalities only on 30-2 protocol for AVF testing, two had abnormalities only on 10-2 protocol, whereas five patients had abnormalities on both protocols. SD-OCT abnormalities were present in all patients with retinopathy. Hydroxychloroquine retinopathy was prevalent in the study cohort and significantly associated with a higher daily dose of HCQ (mg/kg real body weight).

Use of Hydroxychloroquine and Risk of Heart Failure in Patients With Rheumatoid Arthritis.

To examine the relationship between the use of hydroxychloroquine (HCQ) and risk of developing heart failure (HF) in rheumatoid arthritis (RA). In this nested case-control study, cases were Olmsted County, Minnesota residents with incident RA (based on 1987 American College of Rheumatology criteria) from 1980 to 2013 who developed HF after RA incidence. Each case was matched on year of birth, sex, and year of RA incidence with an RA control who did not develop HF. Data on HCQ use including start and stop dates, as well as dose changes, were reviewed and used to calculate HCQ duration and cumulative dose. Age-adjusted logistic regression models were used to examine the association between HCQ and HF. The study identified 143 RA cases diagnosed with HF (mean age 65.8 yrs, 62% females) and 143 non-HF RA controls (mean age 64.5, 62% female). HCQ cumulative dose was not associated with HF (OR 0.96 per 100-g increase in cumulative dose, 95% CI 0.90-1.03). Likewise, no association was found for patients with a cumulative dose ≥ 300 g (OR 0.92, 95% CI 0.41-2.08). The HCQ duration of intake in years prior to index was not associated with HF (OR 0.98, 95% CI 0.91-1.05). Use of HCQ was not associated with development of HF in patients with RA in this study. Further studies are needed to understand the effect of higher doses of HCQ on the development of HF in RA.

HCQ prophylaxis in COVID-19 did not show any QTc prolongation in Healthcare workers

BackgroundHCQ is a commonly recommended drug for the prophylaxis of COVID-19. One of its rare side-effect includes QTc prolongation. MethodsThis was a prospective, cross sectional and observational study conducted on Hydroxychloroquine (HCQ) among Healthcare Workers (HCWs) at Max Super Speciality Hospital, Saket, New Delhi, India. A 3-lead ECG (only limb leads, it does not require chest leads) was performed. The QTc cut offs were pre decided, QTC < 470 ms for males and <480 ms for females was considered within the normal limits and anything above this was regarded as QTc prolongation. ResultsThere were 274 HCWs enrolled into the study, including 175 males and 99 females. Majority of the HCWs were young and had a mean age of 32.19 ± 9.29 years. Out of these, 218 were taking HCQ as per the Indian Council of Medical Research (ICMR) guidelines. The median cumulative dose being taken was 1600 mg and the median QTc of these participants was 390 ms in males and 391.5 ms in females. Subsequently, 33 participants were followed-up and found to have a median QTc of 389 ms and a cumulative dose of HCQ as 2000 mg. ConclusionIn conclusion, ours is a first study in the middle of the pandemic which showed that HCQ prophylaxis in young HCWs without comorbidities did not show any QTc prolongation.