Detecting Hydroxychloroquine Retinal Toxicity using a Novel Multifocal Electroretinography Stimulus
Bibliographic record
Abstract
Abstract Purpose To evaluate a novel 5‐ring multifocal electroretinogram (mfERG) stimulus as a screening test for detecting hydroxychloroquine (HCQ) retinopathy. Study Design A stratified case‐control study conducted in accordance to the Standards for Reporting of Diagnostic Accuracy Studies (STARD). Methods Consecutive patients referred to the University of Ottawa for HCQ retinopathy screening from July 2018 to September 2018 underwent testing using a novel 5‐ring mfERG stimulus and the standard 61‐hexagon mfERG stimulus. Patients with amblyopia, high myopia or hyperopia, coexisting retinal disease, and prior retinal surgery were excluded. mfERG parameters were compared between protocols and against cumulative dose (CD), dose by real body weight (RBW), and duration of HCQ therapy. Ring amplitudes (R1‐R5) and ring ratios (R1‐R4/R5) were collected for each stimulus protocol. mfERG data was collected from an additional group of controls with no previous exposure to HCQ. Stata 15.1 software was used to perform the regression analyses, and to compute Spearman correlation coefficients between variables. Results 24 eyes (10 patients, 2 controls) were included in the final analysis. The novel R2 and R3 P1 amplitudes and R2/R5 were moderately correlated with the respective R2 (r = 0.434, p = 0.034) and R3 (r = 0.429, p = 0.036) P1 amplitudes and R2/R5 (r = 0.422, p = 0.040) of the 61‐hexagon stimulus. The novel R2 P1 amplitude was highly correlated with CD (r = −0.687, p < 0.001), treatment duration (r = −0.687, p < 0.001), and dose by RBW (r = −0.763, p < 0.001). Similarly, novel R2/R5 was highly correlated with CD (r = −0.743, p < 0.001), treatment duration (r = −0.743, p < 0.001), and dose by RBW (r = −0.567, p = 0.004). The correlations between the 61‐hexagon stimulus R2/R5 and HCQ risk factors also reached significance but were not as robust. Linear regression analysis showed that CD may account for almost half of the variance in the novel R2/R5. (r2 = 0.486, R2/R5 = 9.68063 + cumulative dose ‐0.00286) Conclusions The 2016 AAO guidelines focused primarily on the use of subjective functional testing and objective structural testing and relegated mfERG based on a lack of accessibility. This pilot study describes a new 5‐ring mfERG protocol specific for HCQ retinopathy screening and suggests equivalence to the 61‐hexagon protocol at characterizing parafoveal function. This novel 5‐ring stimulus has a significantly shorter acquisition period and the ring design may be more sensitive to HCQ induced electrophysiologic change in the parafoveal region. R2 P1 amplitude and R2/R5 ring ratios acquired using this novel mfERG stimulus are strongly correlated to treatment duration and HCQ dosing. Additional prospective cohort studies are needed to validate this novel stimulus which may decrease the resource burden associated with objective functional testing.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".