TAMOXIFEN
It’s a nonsteroidal estrogen antagonist used in treatment of advanced breast carcinoma & as adjuvant therapy after surgical resection of early disease.
Risk factors for retinopathy
Toxic doses – 60-100mg/day
Total dosage > 100g
Recent studies has shown that chronic low dosage (10-20mg/day) with as little as 7.7g total dose can also ocular toxicity.
Symptoms – decreased VA & color vision
Ocular signs –
Anterior segment - vortex keratopathy
Fundus – bilateral multiple, yellow, crystalline, ring like deposits in the maculae. These persists even on cessation of treatment
macular edema
punctuate retinal pigmentary changes
Work up
- FFA – late focal staining in the macula consistent with CME.
- ERG – decreased photopic & scotopic a & b wave amplitude.
Histopathology – intraretinal deposits in the nerve fiber layer & inner plexiform layer
More numerous in the paramacular areas.
Visual function & edema improve after discontinuation of the drug, but the refractile deposits remain.
Differential diagnosis – juxtafoveal telangiectasia – FFA to rule out
In a confirmed case of tamoxifen toxicity with visual complaints, the drug must be stopped.
Since maculopathy is rare , routine screening is not needed with current loe dose therapy ( 10-20mg/day).
CANTHAXANTHINE
It is a naturally occurring carotenoid used as a tanning agent. It is also used as a food coloring agent, for skin pigmentation in vitiligo & treatment of photosensitivity in psoriasis & erythrocytic porphyrias.
Histopathology – lipid soluble crystals are found pathologically in the entire inner retina
& ciliary body.
Risk factors for retinopathy
dose related ( >19gms over 2 yrs)
Symptoms - most of the patients are asymptomatic.
Fundus – bilateral ring-shaped deposition of yellow orange crystals in the superficial retina arranged in a doughnet shape at the posterior poles surrounding the fovea.
Work up
FFA – normal
With discontinuation of treatment, deposits may slowly clear over many years.
METHOXYFLURANE
It is a inhalational anesthetic agent.Mechanism
It is metabolized to oxalic acid which combines with calcium to form insoluble calcium oxalte salt. This is deposited in various body tissues & the RPE & inner retina in the eye.
Ocular signs
Fundus – numerous yellow-white punctuate lesions in the posterior pole & periarterially.
CLOFAZIMINE
Used to treat dapsone resistant leprosy, pyoderma gangrenosum, discoid lupus.
Symptoms
Visual acuity mildly affected, with reduced scotopic, photopic and flicker ERG amplitudes
Ocular signs – crystals may accumulate in the cornea
Bull’s eye maculopathy with pigmentary retinopathy
Cessation of treatment may result in clearence but does not appear to affect the retinopathy.
CISPLATIN & CARMUSTINE
Used for treatment of malignant glioma & metastatic breast cancer
Three types of retinal toxicity
- Pigmentry maculopathy with marked decreased VA, and abnormal electrophysiologic testing.
- Cotton wool spots, intraretinal hemorrhages, macular exudates & optic neuropathy with disc swelling
- Vascular retinopathy or optic retinopathy include arterial occlusion, vasculitis & papillitis.
Other effects – orbital pain, chemosis, secondary glaucoma, internal ophthalmoplegia and cavernous sinus syndrome
Visual loss is usually progressive.
TALC
Usually occurs in intravenous abusers.
Mechanism - oral medications like methylphenidate hydrochloride (Ritalin) or methadone contains talc as inert filler material. Intravenous drug abusers crush these medications and create an aqueous suspension by adding water and heating the mixture. This solution is subsequently drawn up into syringe and injected intravenously. The talc particles embolize to the pulmonary vasculature and get trapped. After repeated injections, collateral vasculature develops, allowing the particles to enter the systemic circulation and embolizes to other organs, including the eye.
Ocular signs
Due to embolic phenomenon on retinal vasculature, a characteristic picture of an ischemic retinopathy begins to develop. Capillary nonperfusion, microaneurysm formation, cotton wool spots and venous loops.
Severe cases may develop optic disc & peripheral new vessels and vitreous hemorrhage.
Treatment - laser photocoagulation for new vessels and vitrectomy for hemorrhage.
ORAL CONTEACEPTIVE
CRVO, CRAO, Cilioretinal artery occlusion have been reported.
AMINOGYCOSIDE
Intravitreal injection for bacterial endophthalmitis, prophylactic intravitreal injection after pars plana vitrectomy, prophylactic subconjunctival injections after ocular surgery, and with the use of small amounts in the infusion fluid during cataract extraction.
Preservatives add to the toxicity.
Occurs after the inadvertent injection of massive doses.
Gentamicin is the most toxic aminogycoside followed by tobramycin and amicacin.
Mechanism
Affects the retinal vasculature.
Formation of abnormal lamellar lysosomal inclusions in the RPE.
Necrosis of outer then inner segments.
Histopathologic changes - vascular occlusion by granuocytes
Risk factors for retinopathy
Injection directed towards posterior pole with the bevel toward the retina
Increased rate off injection
Ocular signs
Superficial & intraretinal hemorrhages, retinal edema, cotton wool spots, arteriolar narrowing & venous beading
Rubeiosis iridis, neovascular glaucoma, pigmentary retinopathy and optic atrophy in late stages.
Work up
FFA – severe vascular nonperfusion in the acute stages.
Prevention by inadvertent use
If inadvertent use occurs, immediate pars plana vitrectomy with posterior segment lavage
INTERFERON
Mechanism
Immune complex deposition & activated complement C5a with leucocyte infilteration.
Risk factors for retinopathy
More frequent in diabetic & Hypertensive patients
Changes noted within 4-8 weeks of therapy
Ocular signs
Multiple cotton wool spots with retinal hemorrhages.
Optic disc edema, BRAO, BRVO, CME
EPINEPHRINE
Macular edema in aphakic eyes.
CME indistinguishable from clinically & angiographically from postoperative ahakic CME.
CME resolves with cessation of epinephrine.
Should be avoided in the tratment of the glaucomatous aphalic and pseudophakic eye.
NICOTINIC ACID
Niacin used in high doses to reduce serum lipid & cholestrol levels.
Blurred vision & paracentral scotoma.
FFA – typical CME
With cessation of drug cme resolves, vision returns to normal.
LATANOPROST
2-5% patients develops CME , which resolves after discontinuation.
SULFA DERIVATIVES
Ciliary body swelling leads to anterior chamber shallowing.
Retinal folds as a result of vitreous traction on the macula that is caused by the forward shift of the lens & iris.
CORTICOSTEROID PREPARAEATION
Intravitreal injections have been shown to cause retinal necrosis. Corticosteroid themselves probably have minimal toxic effects on the retina but the vehicles causes the retinal necrosis.
NITROFURANTOIN
May cause crystalline retinopathy.
RIFABUTIN
Used for Mycobacterium avium complex in AIDS patients
Toxic dose –……….. mg/day
Causes anterior uveitis, posterior vitritis and retinal vasculitis
CIDOFOVIR
Used I treatment of CMV retinitis
Cause anterior uveitis, hypotony and visual loss.
Fewer side effects on retina.
CARDIAC GLYCOSIDES
Direct toxicity on photoreceptors
Blurred vision, scintillating scotomas& xanthopsia.
Reversible with discontinuation of drug
METHANOL
Occasionally ingested by alcoholics
Toxicity – caused by formic acid
Visual blurring and field deficits within 18 hrs
Early fundus changes – optic nerve hyperemia & retinal edema
Late – optic atrophy
Treatment – early haemodialysis is effective in removing methanol from the body, but if visual recovery is not evident by 6 days, it often remains permanently decreased.
