Opthalmic side effects of systemic medications from kanski and form question crisp and good
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Ophthalmic Side Effects of Systemic Medications (Kanski's Clinical Ophthalmology, Ch. 21 – Drug-Induced Disorders)
Organized by anatomical site
Eyelids
| Drug | Effect |
|---|---|
| EGFR inhibitors (e.g. erlotinib) | Dose-dependent trichomegaly (common); blepharitis, dry eye (less common); cicatricial ectropion (rare) |
| Imatinib | Periorbital oedema in up to two-thirds of patients (5-8 weeks after starting); occasional ptosis |
| Dasatinib | Eyelash poliosis (reversible) |
| Ipilimumab | Thyroid-eye-disease-like signs; responds to systemic steroids |
| Bortezomib | Recurrent chalazia |
| Isotretinoin | Blepharoconjunctivitis, xerosis, corneal opacities, night blindness, pseudotumour cerebri (all reversible) |
Cornea
- Vortex keratopathy (cornea verticillata): golden-brown whorl-like epithelial deposits, classically caused by amiodarone, chloroquine/hydroxychloroquine, chlorpromazine, tamoxifen, indomethacin.
- Amiodarone: virtually all patients develop keratopathy, dose- and duration-related, usually reversible.
- Chloroquine keratopathy: unlike its retinopathy, bears no relation to dose/duration; usually reversible.
Lens
- Corticosteroids (systemic or topical) → posterior subcapsular cataract.
Glaucoma
- Steroid-induced glaucoma: ~1 in 3 people are "steroid responders." IOP rise usually 2-4 weeks after starting topical/periocular/intravitreal/systemic steroid (intravitreal triamcinolone effect lasts 2-4 months; Ozurdex up to 6 months). Risk factors: pre-existing glaucoma/OHT, family history, high myopia, young age, rheumatoid arthritis. Management: stop/taper steroid or switch to a "softer" steroid (fluorometholone, rimexolone, loteprednol); ~3% have persistent IOP rise needing medical/surgical treatment.
- Topiramate, sulfonamides → acute angle-closure glaucoma (ciliochoroidal effusion/lens-iris shift), often bilateral, early in treatment.
Retina
- Chloroquine and hydroxychloroquine: bull's-eye maculopathy from cumulative toxicity; hydroxychloroquine much safer than chloroquine, especially if kept under 5 mg/kg real body weight/day. Risk rises with dose, duration (>5 years), renal impairment, and concurrent tamoxifen. Screening: baseline exam plus annual screening (after 5 years) with 10-2 visual fields, spectral-domain OCT, and fundus autofluorescence.
- Phenothiazines (thioridazine, chlorpromazine): pigmentary retinopathy, especially with thioridazine at high doses.
- Tamoxifen: crystalline maculopathy (refractile deposits), can occur even at standard doses; risk factor requiring closer chloroquine screening.
- Drug-induced crystalline maculopathies: tamoxifen, canthaxanthin, methoxyflurane, talc (IV drug use).
- Bevacizumab (intravitreal/systemic) and other anti-VEGF agents: retinal effects with prolonged systemic use.
Optic nerve
| Drug | Effect |
|---|---|
| Ethambutol | Dose-related optic neuropathy - typically bilateral, symmetric, progressive; red-green dyschromatopsia often precedes visual loss; usually reversible if stopped early |
| Isoniazid | Optic neuropathy, can potentiate ethambutol toxicity |
| Amiodarone | Optic neuropathy in 1-2% of long-term users, probably from demyelination, not clearly dose-related; must be distinguished from non-arteritic AION |
| Vigabatrin | Concentric visual field constriction |
| Methotrexate | Rare optic neuropathy |
| Sildenafil | Transient blue-tinged vision (cyanopsia) via PDE6 cross-inhibition; rare association with NAION |
| Rifabutin, cidofovir, bisphosphonates, sulfonamides, fluoroquinolones, TNF inhibitors | Various - uveitis (rifabutin, cidofovir, bisphosphonates), optic neuritis/demyelination (TNF inhibitors) |
Crisp Exam-Style Questions (with answers)
Q1. Which systemic drug produces vortex keratopathy in virtually all patients, often soon after starting treatment, related to dose and duration?
A) Chloroquine B) Amiodarone C) Ethambutol D) Isoniazid
Q2. The maximum "safe" dose of hydroxychloroquine to minimize retinal toxicity risk is:
A) 6.5 mg/kg ideal body weight/day B) ≤5 mg/kg real body weight/day C) 10 mg/kg/day D) 250 mg/day fixed dose
Q3. Which visual field test combined with which imaging modalities form the standard hydroxychloroquine screening protocol?
Answer: 10-2 automated visual field, spectral-domain OCT, and fundus autofluorescence (plus baseline exam).
Q4. A patient on ethambutol develops difficulty distinguishing red from green before any drop in visual acuity. This finding is an early sign of:
Answer: Ethambutol-induced (dose-related, usually bilateral symmetric) optic neuropathy - red-green dyschromatopsia typically precedes overt visual loss.
Q5. Which class of drug is most classically associated with acute bilateral angle-closure glaucoma via ciliary body/lens-iris shift, often within days to weeks of starting?
A) Beta-blockers B) Sulfonamides / Topiramate C) Statins D) ACE inhibitors
Q6. What proportion of the general population are "steroid responders" who develop significant IOP elevation with potent topical steroid use?
Answer: Approximately 1 in 3 (one-third).
Q7. Name two "softer" corticosteroids with lower propensity to raise IOP, useful when steroid therapy must continue.
Answer: Fluorometholone 0.1%, rimexolone 1%, or loteprednol etabonate.
Q8. Which anti-arrhythmic drug can cause an optic neuropathy in 1-2% of long-term users that must be distinguished from non-arteritic anterior ischaemic optic neuropathy (NAION)?
Answer: Amiodarone.
Q9. Tamoxifen use is a recognized risk factor requiring closer screening in patients also taking which antimalarial drug, due to additive retinal toxicity risk?
Answer: Chloroquine (and hydroxychloroquine).
Q10. Sildenafil's transient effect on color vision (typically a blue tinge) is due to its cross-inhibition of which retinal enzyme?
Answer: PDE6 (retinal phosphodiesterase).
Q11. Which tyrosine kinase inhibitor used for CML causes periorbital oedema in up to two-thirds of patients, typically 5-8 weeks after starting?
Answer: Imatinib.
Q12. Isotretinoin therapy for acne can cause which four ocular surface/visual effects, all reversible on discontinuation?
Answer: Blepharoconjunctivitis, xerosis (dry eye), corneal opacities, and night blindness (with rare pseudotumour cerebri).
Source: - Kanski's Clinical Ophthalmology: A Systematic Approach, 10th ed., Chapter 21 "Drug-Induced Disorders" (Eyelids, Cornea, Lens, Retina, Optic Nerve sections), and Glaucoma chapter section on Steroid-induced glaucoma.
This is stable, well-established textbook content (drug ocular toxicity mechanisms and screening protocols), so I did not run an additional PubMed check - there's no fast-moving controversy here beyond the well-known 2016 AAO hydroxychloroquine screening revision, which is already reflected in the dosing/screening figures above. Let me know if you want this expanded into a longer MCQ bank, flashcards, or a printable PDF/Word document.
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