How to interpret an Optical Coherence Tomography (OCT) report for hydroxychloroquine toxicity?

How to Interpret OCT Reports for Hydroxychloroquine Toxicity

Look for localized parafoveal thinning of the photoreceptor layers and focal interruption of the ellipsoid zone (outer segment structural lines) on spectral-domain OCT, as these are the most specific early anatomic markers of hydroxychloroquine retinopathy. 1

Key OCT Findings to Identify

Early Toxicity Signs (Most Important)

• Focal interruption or loss of the ellipsoid zone (previously called the inner segment/outer segment junction) in the parafoveal region—this is often the earliest detectable structural change 1, 2
• Attenuation of the parafoveal ellipsoid zone with loss of a clear continuous interdigitation zone, which may occur even when visual fields remain normal 2
• Localized thinning of photoreceptor layers in characteristic patterns: parafoveal distribution in non-Asian patients, or near the vascular arcades in Asian patients 1

Important Technical Considerations

• Wider scanning protocols are essential for Asian patients (30° line scans) because toxicity often manifests peripherally near the arcades rather than parafoveally 1
• The outer retinal thickness typically remains normal until focal photoreceptor loss develops, so you're looking for new focal abnormalities rather than gradual global thinning 1
• Ganglion cell analysis (ganglion cell + inner plexiform layer) may show concentric thinning in the affected area and can detect toxicity even when standard thickness maps appear normal 3

Progression Patterns by Disease Stage

Early Stage (Pre-RPE Damage)

• Patchy parafoveal photoreceptor damage visible on OCT 4
• Ellipsoid zone breadth remains relatively constant after drug cessation 4
• Minimal foveal thinning (approximately 4 μm/year) 4
• Critical point: Damage detected at this stage can stabilize without serious visual loss if hydroxychloroquine is discontinued 1, 4

Moderate Stage

• 50-100% parafoveal ring of OCT thinning but intact retinal pigment epithelium 4
• Some deepening of parafoveal loss but ellipsoid zone breadth remains stable 4
• Foveal thinning approximately 4 μm/year 4

Severe Stage (Bull's-Eye Maculopathy)

• Visible RPE damage with progressive foveal thinning (approximately 7 μm/year) 4
• Loss of ellipsoid zone approximately 100 μm/year 4
• Progressive expansion of damage even after drug discontinuation 4
• This stage should no longer occur with proper screening 1

Critical Interpretation Pitfalls

When OCT Changes Precede Visual Field Defects

• OCT abnormalities may develop before Humphrey visual field defects appear—this is a crucial finding that emphasizes why OCT cannot be omitted from screening 2
• If you see suspicious OCT changes with normal visual fields, consider ancillary testing (multifocal ERG, fundus autofluorescence, microperimetry) for confirmation 2, 1

Handling Borderline or Subtle Findings

• Early OCT changes can be subtle and hard to distinguish from normal variation 1
• Retinopathy develops slowly over years, so there is time to recheck suspicious findings after a few months 1
• Do not discontinue hydroxychloroquine based on questionable findings alone—repeat testing or obtain retina consultation with additional objective tests 1
• The decision to stop the drug should involve shared decision-making between patient, prescribing physician, and ophthalmologist, weighing disease severity against visual loss risk 1

Racial and Ethnic Considerations

• European descent patients: Look for parafoveal distribution of photoreceptor damage in the classic ring pattern 1, 5
• Asian descent patients: Examine the pericentral vascular arcade regions carefully, as initial damage often appears peripherally rather than parafoveally 1, 5
• Standard central 10-degree protocols may miss toxicity in Asian patients—use broader scanning patterns 1

Integration with Other Testing

• OCT is more definitive than visual fields when regional thinning is present in a typical pattern, though it may be slightly less sensitive than visual fields or multifocal ERG for earliest detection 1
• Whenever possible, screening should start with OCT as anatomic changes are more specific for detecting toxicity than subjective visual field testing 1
• Fundus autofluorescence can reveal early parafoveal or extramacular photoreceptor damage as increased autofluorescence that may precede OCT thinning 1

What NOT to Rely On

• Time-domain OCT lacks sufficient resolution to detect early toxic changes 1
• Fundus examination and ophthalmoscopy detect only late-stage disease and should not be used for screening 1
• Normal visual acuity is maintained until severe stages, so it cannot be used to rule out toxicity 1, 5