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Background The location of Plasmodium falciparum within the body is determined by the life cycle of the parasite; young rings are in the peripheral blood, whereas mature parasites are sequestered in deep tissues. We can calculate a "ring ratio," the proportion of parasites in the periphery to the total number of parasites in the body. Artesunate acts on all parasite life stages, whereas quinine is effective only on sequestered parasites. Children with cerebral malaria (CM) treated with artesunate clear parasites faster than those treated with quinine. In this study, we established the relationship between ring ratio and parasite clearance rate and used the ring ratio to determine if the benefit derived from artesunate treatment could be attributed to its broader effect on life cycle stages. Methods Ring ratios were calculated for 400 hospitalized children with CM in Blantyre, Malawi between 2010 and 2019 (quinine: 2010–2013, artesunate: 2014–2019). Results In both treatment groups, parasite clearance rates were positively associated with the ring ratios, with a stronger association in the artesunate era than the quinine era. In the quinine era, an increase of 1-unit log10 difference between parasitemia and plasma P falciparum histidine-rich protein 2 (a proxy for ring ratio) resulted in a 0.27-unit increase in the parasite clearance rate, whereas in the artesunate era an equal increase resulted in a 0.41-unit increase (P =.04 for the difference). Conclusions This analysis provides in vivo evidence supporting the hypothesis that more rapid parasite clearance rates in artesunate recipients are due to its superiority over quinine in killing ring-stage parasites. [ABSTRACT FROM AUTHOR]

Purpose: Multifocal electroretinogram (mfERG) shows great utility as a screening tool to detect early hydroxychloroquine (HCQ) retinopathy, but its widespread use is limited by the lack of accessibility and long test duration. In this study, we evaluated a novel concentric 5-ring mfERG stimulus to provide a simplified and rapid protocol for screening HCQ toxicity. Methods: Patients referred for HCQ retinopathy screening were consented to this observational cross-sectional study. Patients with amblyopia, high refractive error (more than 8 diopters), other retinal diseases precluding appropriate evaluation or history of retinal surgery were excluded. The data were collected from patients undergoing HCQ screening at a single center from July 2019 to March 2020. Patients were tested with the new concentric 5-ring mfERG stimulus, standard 61-hexagon mfERG stimulus, spectral domain optical coherence tomography and automated 10-2 visual fields. For the main outcome, the 5-ring mfERG was compared to 61-hexagon stimulus to determine the time-to-test completion and assess the association between ring (R1–R5) amplitude and ring ratio compared against cumulative dose, dose by real body weight and duration of therapy using Pearson correlation. Results: In total, 52 patients (104 eyes; 5 males and 47 females) were recruited with a mean age of 59 years (range 23–85 years). The 5-ring protocol was markedly quicker to perform (1.3 ± 0.2 min; mean (SD)) compared to the 61-hexagon protocol (5.2 ± 0.6 min), p < 0.0001; n = 10 patients. The new R2/R5 ring ratio showed a moderate correlation with daily dose (r = − 0.640), cumulative dose (r = − 0.581) and duration of therapy (r = − 0.417). Similar correlations were observed with the new R2/R4 ring ratio which were not significantly different from the new R2/R5 correlation coefficients. The new R2/R5 ring ratio demonstrated a stronger correlation with daily (p = 0.002) and cumulative dose (p = 0.0001) compared to the 61-hexagon stimulus. Conclusions: In this exploratory study, our novel 5-ring mfERG protocol significantly shortened data acquisition time while providing comparable results to the standard 61-hexagon stimulus for detecting HCQ-induced electrophysiological changes that are correlated with HCQ dosages and treatment duration. Our protocol has the potential to be more clinically practical by simplifying routine screening. [ABSTRACT FROM AUTHOR]

Purpose: Pericentral visual field changes and disruption of the ellipsoid layer on spectral domain optical coherence tomography (SD-OCT) are the main features of antimalarial retinal toxicity. C-Scan OCT or “en face” enables a topographic frontal view of the changes observed within the different retinal layers in particular the ellipsoid layer. The aim of this prospective study was to compare multifocal ERG (mfERG) responses with the results of C-Scan OCT (“en face” OCT) in patients with abnormal visual field and to analyze relationships between the structural and functional abnormalities.Methods: In 354 consecutive patients screened for antimalarial toxicity between January 1, 2014 and December 31, 2016, central visual field, mfERG recording, C-Scan OCT and short-wavelength fundus autofluorescent imaging were performed.Results: Among the 17/354 patients with abnormal central visual field results, all presented with abnormalities on the mfERG at least in one eye. In 16/33 eyes, there was a good concordance between focal loss of the mfERG response and the disruption of the ellipsoid layer on C-Scan OCT. In one eye with characteristic changes in the ellipsoid layer on the C-Scan OCT, the mfERG was normal, whereas in three eyes the mfERG was abnormal in eyes with a normal C-Scan OCT.Conclusions: The contribution of the C-Scan OCT changes remains difficult to establish as there is no strict concordance with the local ERG responses. Although C-Scan OCT technology provides a new approach in analyzing focal abnormalities in the photoreceptor-retinal pigment epithelium interface, the sensitivity of this method compared with mfERG and other tests (central visual field, B-Scan OCT) needs to be evaluated. This study is still ongoing on a larger cohort. [ABSTRACT FROM AUTHOR]

Purpose: To compare retinal function by using fundus-guided microperimetry (MP) and multifocal electroretinography (mfERG) for detecting hydroxychloroquine (HCQ) maculopathy., Methods: Forty-six eyes of 25 patients referred to our clinical practice for HCQ maculopathy assessment and 3 groups of normal control subjects were evaluated by mfERG and MP. Macular structure was assessed using spectral-domain optical coherence tomography (SD-OCT). Ring ratios from the three innermost mERG rings were compared with average sensitivity of each MP ring at approximately equivalent distances from the fovea. HCQ toxicity was defined as an mfERG ring ratio or mean MP ring sensitivity >2 standard deviations below the normal mean. The sensitivity and specificity of MP to detect HCQ toxicity relative to mfERG were evaluated., Results: MP rings MR2 and MR3 were positively correlated with corresponding mfERG ring ratios (r = 0.52, P = 0.002 and r = 0.56, P < 0.001 respectively). Ring 2 and ring 3 measures of MP and mfERG were significantly worse in HCQ eyes than controls ( P < 0.001). The sensitivity of MP to detect toxicity for MR1 through MR3 ranged from 33% to 88%, whereas specificity ranged from 72% to 85%. Through rings 1 to 3, the frequency of abnormal function ranged from 20% to 48% for MP, 11% to 35% for mfERG, and 41% to 45% for SD-OCT., Conclusions: The frequency of detection of HCQ toxicity with MP was greater than with mfERG. MP showed an overall good sensitivity and moderate specificity in detecting HCQ-induced functional deficits., Translational Relevance: Results from this study may allow clinicians to improve screening accuracy for HCQ toxicity by using the alternative modality of MP., (Copyright 2019 The Authors.)