What are the potential eye side effects of Hydroxychloroquine (HCQ)?

Hydroxychloroquine Eye Side Effects

Hydroxychloroquine can cause irreversible retinal damage that may progress even after discontinuation of the medication, with the primary risk being retinopathy that can lead to permanent vision loss if not detected early. 1, 2

Primary Retinal Toxicity

Hydroxychloroquine (HCQ) retinopathy is characterized by:

• Early stages:

  • Photoreceptor damage in the retina without visible fundus changes
  • Parafoveal pattern in patients of European descent
  • Extramacular pattern near the arcades in patients of Asian descent 1
  • No visual symptoms initially (visual acuity remains excellent) 1

• Progressive stages:

  • Paracentral scotomas (blind spots near central vision) 1
  • Retinal pigment epithelium (RPE) involvement 1
  • Bull's eye maculopathy in advanced cases 3
  • Eventual loss of central vision if drug exposure continues 1

• Advanced stages:

  • Cystoid macular edema 1
  • Widespread RPE and retinal atrophy 1
  • Loss of visual acuity, peripheral vision, and night vision 1

Risk Factors for Retinopathy

The primary risk factors include:

• Daily dosage >5.0 mg/kg real body weight (most critical risk factor) 1, 2
• Duration of use >5 years (risk increases sharply after 10 years) 1, 4
• Renal disease (subnormal glomerular filtration rate) 1, 2
• Concurrent tamoxifen use (increases risk by 4.5 times) 4
• Pre-existing macular disease 1

Prevalence and Risk Statistics

• Overall prevalence of retinopathy: 7.5% in long-term users 4
• Risk with proper dosing (<5.0 mg/kg real weight):
  • <1% in first 5 years
  • <2% up to 10 years
  • Rises to almost 20% after 20 years 1, 4

Other Ocular Side Effects

• Corneal changes: Whorl-like intraepithelial deposits (verticillata) 1
  • Less frequent with HCQ than with chloroquine
  • Not associated with visual loss
  • Usually reversible, unlike retinopathy
  • Not a direct marker for retinal damage

Screening Recommendations

Early detection is critical as retinopathy is not reversible but can be stabilized if detected early:

• Baseline examination: Within first year of starting HCQ 1, 2

  • Best corrected visual acuity
  • Automated threshold visual field of central 10 degrees
  • Spectral domain optical coherence tomography (SD-OCT)

• Annual screening:

  • Begin after 5 years of use if no risk factors 1
  • Begin immediately if risk factors present 1, 2
  • Include both SD-OCT and automated visual fields 1
  • For Asian patients: Use wider field testing (24-2 or 30-2) 1

Important Clinical Considerations

• Retinopathy can progress even after drug discontinuation 1, 5
• Early detection before RPE damage limits progression after discontinuation 1
• Inner retina is generally not involved in HCQ toxicity 6
• No clinically apparent warning signs on SD-OCT until actual appearance of retinopathy 6

Common Pitfalls to Avoid

1. Relying solely on visual acuity: Visual acuity remains excellent until severe stages 1
2. Waiting for symptoms: Most patients are asymptomatic in early stages 1
3. Using only fundus examination: Bull's eye changes are late findings 1
4. Calculating dose by ideal body weight: Real body weight is more accurate for risk assessment 1, 4
5. Stopping medication prematurely: Uncertain findings should be verified before discontinuation 1

Early detection through proper screening is essential to prevent irreversible vision loss from hydroxychloroquine retinopathy, as the damage cannot be reversed once it occurs.