Correct Answer: B. Chloroquine
Chloroquine is a lipophilic weak base that accumulates in melanin-rich tissues, particularly the cornea, retina, and skin. The drug binds to melanin and concentrates in corneal epithelium, leading to characteristic corneal deposits (whorl-like or crystalline opacities) that are pathognomonic for chloroquine toxicity. These deposits are reversible and typically asymptomatic, appearing as fine vertical lines in the corneal epithelium on slit-lamp examination. This is a well-documented adverse effect in Indian patients receiving chloroquine for malaria prophylaxis, rheumatoid arthritis, or systemic lupus erythematosus. The mechanism involves the drug's high lipophilicity (pKa 8.4) allowing it to cross the blood-aquine barrier and bind to corneal melanin. While chloroquine can also deposit in the retina (causing more serious retinopathy), corneal deposition is the more characteristic and earlier finding. This distinguishes chloroquine from other antimalarials and DMARDs used in Indian clinical practice.
Why the other options are wrong
A. Sulfasalazine — Sulfasalazine is a sulfonamide-based DMARD used in rheumatoid arthritis and inflammatory bowel disease in India. While it causes ocular toxicity (mainly keratitis sicca and reversible corneal opacities), it does not characteristically deposit in the cornea as a primary mechanism. Its ocular effects are primarily inflammatory rather than deposition-based, making it incorrect for this specific question about drug deposition. C. Methotrexate — Methotrexate, a folate antagonist DMARD widely used in India for rheumatoid arthritis and malignancies, causes ocular toxicity primarily through retinal and conjunctival involvement (conjunctivitis, retinal hemorrhages) rather than corneal deposition. It does not accumulate in melanin-rich corneal tissues, and its adverse effects are dose-dependent systemic toxicity rather than tissue-specific deposition. D. Leflunomide — Leflunomide, a newer DMARD used in Indian rheumatology practice, causes ocular adverse effects primarily through retinal toxicity and optic neuritis rather than corneal deposition. It lacks the lipophilic, melanin-binding properties of chloroquine and does not characteristically accumulate in corneal epithelium, making it an incorrect choice for corneal deposition.
High-Yield Facts
- Chloroquine corneal deposits appear as fine vertical lines or whorl-like opacities in the corneal epithelium on slit-lamp examination, reversible upon drug discontinuation.
- Chloroquine retinopathy (bull's-eye maculopathy) is irreversible and requires baseline and periodic ophthalmology screening in Indian patients on long-term therapy.
- Melanin binding is the mechanism: chloroquine's lipophilic weak base nature allows accumulation in melanin-rich tissues (cornea, retina, skin, hair).
- Corneal deposits are asymptomatic and appear earlier than retinopathy; they do not affect vision and resolve after stopping the drug.
- Indian DOC for malaria prophylaxis: chloroquine 300 mg base weekly (or 5 mg/kg weekly) for endemic areas; corneal deposits are a known monitoring point.
Mnemonics
CLORO deposits in CORNEA Chloroquine → Cornea (and retina). The 'C' alliteration helps recall that chloroquine uniquely deposits in cornea among antimalarials and DMARDs. Use when comparing ocular toxicity profiles of antimalarials. Melanin Magnet Chloroquine is a lipophilic weak base that acts as a 'melanin magnet'—it binds melanin in cornea, retina, skin. This explains why it deposits in pigmented tissues. Use to understand the pathophysiology of chloroquine toxicity.
NBE Trap
NBE may pair chloroquine with retinopathy (the more serious adverse effect) to lure students into choosing a drug that causes retinal rather than corneal deposition. The trap is confusing corneal deposits (reversible, asymptomatic, early) with retinopathy (irreversible, vision-threatening, late)—the question specifically asks for corneal deposition.
Clinical Pearl
In Indian malaria-endemic regions, patients on chloroquine prophylaxis should undergo baseline slit-lamp examination to detect corneal deposits early. While these deposits are benign and reversible, they serve as a clinical marker of drug accumulation and warrant periodic ophthalmology review to screen for the more serious irreversible retinopathy—a critical point in long-term management of Indian patients with SLE or rheumatoid arthritis on chloroquine.
_Reference: KD Tripathi Pharmacology Ch. 51 (Antimalarials); Harrison Ch. 218 (Malaria)_