Optical Coherence Tomography Detects Hydroxychloroquine Toxicity Severity

Eye examination. Ophthamologist using an optical coherence tomograph (OCT) to measure the thickness of a patient’s retina. This machine images the retina in cross-section. The retina is the light sensitive membrane at the back of the eyeball. Both increases and decreases in retinal thickness can be symptoms of disease, although thickness does decrease with age.
Researchers noted significantly thinner inner retinal thicknesses among participants with higher levels of hydroxychloroquine toxicity.

Hydroxychloroquine (HCQ) toxicity severity levels can be assessed through the use of optical coherence tomography (OCT), according to research published in the British Journal of Ophthalmology. 

Investigators included patients who were exposed to HCQ for at least 5 years (N=85, average duration of exposure:14 years) in a prospective, case-control study. They classified the patients into affected and unaffected groups using the American Academy of Ophthalmology’s (AAO’s) 2016 recommendations. The team stratified affected individuals into 4 subgroups based on severity, which they determined by ellipsoid zone (EZ) band loss (group 1 <100 µm loss, group 2 ≥100 µm, but < 1mm, group 3 ≥1mm, and group 4 foveal island <500 µm intact). The investigators assessed spectral domain-OCT scans in all eyes to determine inner retinal thickness (IRT), outer retinal thickness (ORT), and minimum signal intensity (MI), and compared these measurements across toxicity groups.

They found that 30 of 85 patients exhibited retinal toxicity, with significant differences in ORT and MI noted between each severity group and unaffected eyes. Among affected participants, investigators classified 7 as group 1, 4 as group 2, 12 as group 3, and 7 as group 4. They observed significant differences in IRT for groups 3-4, but not in groups 1-2. ORT and MI discriminated between unaffected and group 1 eyes with the most discrimination at the inner subfields.

Researchers also noted an association between age and toxicity (P =.02) with individuals over the age of 60 accounting for 100% of group 4 members (P =.03).

“Identifying abnormalities using two different quantitative OCT metrics could enhance the confidence of the diagnosis while capturing different characteristics of the underlying pathologic changes,” according to the investigators. “The robustness of detecting toxicity could thus be improved when the two metrics are used in combination, providing independent, objective additions to the current clinical decision-making process.”

Limitations of the study include its single-site and cross-sectional design, with minimal inclusion of participants of Asian ethnicity.

Disclosure: This research was supported by the Colgate-Palmolive Company. Please see the original reference for a full list of disclosures. 


Membreno RF, De Silva T, Agrón E, Keenan TDL, Cukras CA. Quantitative analysis of optical coherence tomography imaging in patients with different severities of hydroxychloroquine toxicity. Br J Ophthalmol. Published online March 14, 2022. doi:10.1136/bjophthalmol-2021-319197