Ocular Toxicity of Systemic Medications

Ocular Drug Toxicity: Intro - Eye Trouble Origins

• Systemic medications can affect any ocular structure: cornea, lens, retina, optic nerve.
• Mechanisms of damage:
  • Direct cellular toxicity.
  • Hypersensitivity reactions.
  • Idiosyncratic responses.
  • Indirect effects (e.g., tear film alteration, ↑IOP).
• Risk factors: dose, duration of use, patient susceptibility (e.g., genetics, renal/hepatic status).

⭐ Many drugs, like chloroquine and thioridazine, bind to melanin in the uveal tract (iris, ciliary body, choroid), leading to accumulation and potential toxicity over time (uveal toxicity).

Corticosteroids: Ocular Effects - Sneaky Sight-Stealers

• Posterior Subcapsular Cataract (PSC): Most common; dose & duration-dependent. Irreversible.
• Steroid-induced Glaucoma: ↑IOP, mimics POAG; higher risk with topical, genetic predisposition.
• Central Serous Chorioretinopathy (CSCR): Can precipitate or worsen existing.
• Infections: Increased risk & severity (e.g., HSV keratitis reactivation, fungal keratitis).
• Delayed Wound Healing: Especially post-ocular surgery.
• Papilledema: Rare, associated with rapid withdrawal (pseudotumor cerebri).

⭐ PSC is the most common ocular side effect of long-term systemic corticosteroid use.

Antimalarials: Retinopathy - Bullseye Beware!

• Chloroquine (CQ) & Hydroxychloroquine (HCQ) can cause irreversible retinopathy.
• Classic sign: Bull's eye maculopathy (late stage).
• Risk factors:
  • HCQ dose > 5 mg/kg/day (actual body weight)
  • CQ dose > 2.3 mg/kg/day
  • Duration of use > 5 years
  • Cumulative dose (e.g., HCQ > 1000g)
  • Renal disease, tamoxifen co-therapy.
• Screening: Baseline exam within 1st year, then annual screening after 5 years of use (or earlier if high risk).
  • Key tests: SD-OCT (detects earliest changes), automated visual fields (10-2).

⭐ Early HCQ retinopathy often manifests as parafoveal RPE disruption or loss of the photoreceptor inner/outer segment junction on SD-OCT (e.g., "flying saucer sign") before visual symptoms or the classic bull's eye maculopathy appears funduscopically. This makes SD-OCT crucial for early detection.

Ethambutol & Amiodarone: Toxicities - Nerve & Cornea Concerns

• Ethambutol:
  • Optic neuropathy (retrobulbar neuritis); dose-dependent (>15-25 mg/kg/day).
  • Symptoms: ↓ VA, red-green dyschromatopsia, central/centrocaecal scotoma.
  • Reversible if detected early; regular vision monitoring is crucial.
  • 📌 "E"thambutol affects "E"yes (optic nerve).
• Amiodarone:
  • Corneal deposits (vortex keratopathy/cornea verticillata); common, dose-related.
  • Usually asymptomatic or mild (halos, glare); reversible upon discontinuation.
  • Optic neuropathy (NAION-like) is rare but serious.

  ⭐ Amiodarone-induced vortex keratopathy, though common (seen in >70% of patients on long-term therapy), rarely causes significant visual impairment.

Other Systemic Drugs: Ocular Risks - Diverse Eye Dramas

Drug Toxicity: Monitoring - Safe Sight Steps

• Pre-Tx: Baseline exam (VA, fundus, special tests). Counsel on symptoms.
• On-Tx: Drug-specific scheduled follow-ups & testing.
• Action: Suspected toxicity? Confirm, stop/modify drug with prescriber, manage.

⭐ Hydroxychloroquine: Annual screening (SD-OCT, VF 10-2) after 5 yrs use, or earlier if high risk.

High‑Yield Points - ⚡ Biggest Takeaways

• Chloroquine/HCQ: Bull's eye maculopathy (irreversible retinal toxicity), corneal verticillata (reversible).
• Ethambutol: Dose-dependent optic neuropathy; presents as retrobulbar neuritis, red-green dyschromatopsia.
• Amiodarone: Corneal verticillata (whorl-like keratopathy, most common), optic neuropathy (less common).
• Corticosteroids: Posterior subcapsular cataract (PSC), ↑IOP leading to steroid-induced glaucoma.
• Tamoxifen: Crystalline retinopathy (refractile deposits), macular edema, corneal opacities.
• Vigabatrin: Bilateral, irreversible, concentric visual field constriction; regular perimetry essential.
• Digitalis: Xanthopsia (yellow-tinged vision), chromatopsia, blurred vision, scotomas.