Retinal toxicity

Hydroxychloroquine may cause retinal toxicity, and patients must have their eyes examined at least annually to detect this abnormality. It is not associated with renal, hepatic, or bone marrow suppression and therefore may be an acceptable treatment option for patients with contraindications to other DMARDs because of their toxicities. 

Originally used in the treatment of malaria, the drugs chloroquine (Aralen) and hydroxychloroquine (Pla-quenil) have also been used to treat rheumatoid arthritis. In the past, these drugs have been used reluctantly because of the fear of retinal toxicity (see Adverse Side Effects ).25 There is now evidence, however, that these agents can be used safely, but they are only marginally effective when compared to other DMARDs. These drugs are therefore not usually the first choice, but they can be used in patients who cannot tolerate other DMARDs, or in combination with another DMARD (e.g., methotrexate) for more comprehensive treatment. 

Chloroquine Aralen Oral Up to 4 mg/kg of lean body weight per day. Periodic ophthalmic exams recommended to check for retinal toxicity. 

Mavrikakis I, Sfikakis PP, Mavrikakis E, et al. The incidence of irreversible retinal toxicity in patients treated with hydroxychloroquine a reappraisal. Ophthalmology. 2003 110 1321-1326. 

He nodded grudgingly. A not unreasonable hypothesis. Many physicians would make the same mistake. But oleander induces retinal toxicity only in chronic cases. ... 

The incidence of retinopathy increases with patient age, and in older patients retinal toxicity appears to be correlated with total drng dosage. 

Chlorpromazine (Thorazine) and thioridazine (Mellaril), both phenothiazine derivatives, are used for their antipsychotic effects in the control of severely disturbed or agitated behavior and in schizophrenia. Thioridazine has a higher incidence of antimuscarinic effects but a lower incidence of extrapyramidal symptoms. Pigmentary changes of the retina have been reported occasionally in association with chlorpromazine therapy, although it is recognized that only thioridazine produces retinal toxicity. 

Thioridazine can cause significant retinal toxicity, leading to reduced visual acuity, changes in color vision, and disturbances of dark adaptation.These symptoms typically occur 30 to 90 days after initiation of treatment. The fundus often appears normal during the early stages of symptoms, but within several weeks or months a pigmentary... 

It is now recognized that the primary clinical fector associated with thioridazine retinopathy is the daily dose of drug. Before becoming aware of the dose-related retinal toxicity, dosages exceeding 1,600 mg daily were commonly prescribed. Few cases of pigmentary retinopathy have been reported, however, with daily dosages of less than 800 mg. 

NSAIDs are commonly used for their analgesic, antiinflammatory, and antipyretic actions in the treatment of arthritis, musculoskeletal disorders, dysmenorrhea, and acute gout.Although these drugs are widely used and are often used for prolonged periods, retinal toxicity is rare. 

Retinal toxicity usually begins within 2 to 14 weeks after intra-arterial infusion of BCNU. Approximately 65% of patients develop retinal complications (Box 35-5). It is common to have loss of vision from the retinopathy, and visual acuity can be reduced to 20/60, to light perception, or even to no light perception. A definite relationship... 

Various other systemic chemotherapeutic agents have been associated with retinotoxic effects. Use of interferon-a, for example, has resulted in various retinal effects, including cotton-wool spot formation, macular edema, capillary nonperfusion, arteriolar occlusion, and intraretinal hemorrhage. Cisplatin and etoposide have induced retinal toxicity in both adults and children. 

Comeal deposits of chloroquine may be asymptomatic or may cause halos around lights or photophobia. These are not a threat to vision and reverse when the dmg is stopped. Retinal toxicity is more serious, however, and may be irreversible. In the early stage it takes the form of visual field defects late retinopathy classically gives the picture of macular pigmentation surrounded by a ring of pigment (the bull s-eye macula). The functional defect can take the form of scotomas, photophobia, defective colour vision and decreased visual acuity resulting, in the extreme case, in blindness. 

Lupus er/thennatosus (affecting tlic skin) Photoprotection is essential. Potent adrenal steroid topically or intralesionally. Hydroxychloroquine or mepacrine. Monitor for retinal toxicity when treatment is long-term.Other agents include auranofin, aceiretin and in severe chilblain LE. thalidomide. A systemic disease, but discoid iupus erythematosus typicaily has no systemic manifestations. 

Retinal toxicity can occur when aminoglycosides are given intravitreally for endophthalmitis. 

Shroyer NF, Lewis RA, Lupski JR. Analysis of the ABCR (ABCA4) gene in 4-aminoquinoline retinopathy is retinal toxicity by chloroquine and hydroxychloroquine related to Stargardt disease Am J Ophthalmol 2001 131(6) 761-6. 

Freeman WR. Retinal toxic effects associated with intra-vitreal fomivirsen. Arch Ophthalmol 2001 119(3) 458. 

Loewenstein A, Zemel E, Vered Y, Lazar M, Perlman I. Retinal toxicity of gentamicin after subconjunctival injection performed adjacent to thinned sclera. Ophthalmology 2001 108(4) 759-64. 

Prolonged therapy can cause a number of adverse reactions in the eyes. Trivial effects are ocular discomfort, conjunctival pain, and increased ocular tension, but mydriasis, photophobia, blurred vision, diplopia, amblyopia, and loss of vision can occur. The most serious complications are retinopathy with reduced retinal sensitivity, and corneal and retinal pigmentation. They are reversible, but improvement is slow. A report on indometacin retinopathy has added more doubt than certainty to the question of the frequency and severity of retinal toxicity (SEDA-14, 93). Patients taking prolonged therapy should have regular ophthalmic examinations. 

The authors added that retinal toxicity of the local anesthetic agent did not affect the visual outcome in this patient. Scleral perforation is a well-known complication of eye blocks for ophthalmic surgery. The incidence with retrobulbar techniques is 0.075% and with peribulbar blocks 0.0002%. When recognized, ocular perforation usually requires a vitreoretinal procedure and is associated with a poor visual outcome. Risk factors include an anxious or oversedated patient, long sharp needles, superior injection, incorrect angle of needle insertion, and myopic eyes. If the intraocular pressure is increased, paracentesis may acutely reduce it, preventing retinal and optic nerve ischemia and possible permanent visual loss. 

Ocular effects, including optic neuritis, papilledema, and retrobulbar neuritis, are uncommon adverse effects of cisplatin-containing cancer chemotherapy. The risk of retinal toxicity is restricted to high-dose cisplatin therapy (for example 200 mg/m over 5 days) and can result in blurred vision and altered color perception, which can persist for several months. In contrast to cisplatin, carbo-platin is seldom involved in drug-induced visual disturbances. In two cases there was a relation between the administration of carboplatin (800-1200 mg/m ) and the occurrence of chnical cortical blindness (122). However, both patients had impaired renal function before the start of therapy with carboplatin. 

Intoxication may present as inebriation and drowsiness similar to ethanol use. Other symptoms are vomiting, diarrhea, delirium and agitation, back and abdominal pain, and clammy skin. Toxic effects usually follow a latent period of several hours. Formate inhibits mitochondrial cytochromes resulting in neurotoxicity. Ocular signs include blurred vision, dilated pupils, and direct retinal toxicity with optic disc hyperemia and ultimately permanent blindness [91]. Cerebral hemorrhagic necrosis has been reported [92]. Severe poisoning may result in Kussmaul respiration, inspiratory apnea, coma, and death. Urine samples may have the characteristic smell of formaldehyde. An elevated serum osmolal gap from methanol will be evident early in presentation but may disappear after approximately 12 hours. At this time, an elevated anion gap metabolic acidosis from retained formate may be evident. 

Quinine The antimalarial agent quinine is derived from the bark of the cinchona tree along with several other alkaloids and salicylate (aspirin). Many of these agents produce similar toxic features (cinchon-ism) in patients with excessive intake, but only quinine produces blindness. Cinchonism consists of abdominal pain and vomiting, ringing in the ears (tinnitus), and confusion. Visual loss after quinine overdose is due to direct retinal toxicity, although until recently it was believed to be due to spasm of the arterial blood supply to the retina. Treatment is difficult, but limited evidence suggests charcoal hemoperfusion may be beneficial (hemoperfusion is similar to hemodialysis, except in place of a semi-permeable membrane to filter the toxin from the blood, charcoal is used to bind the toxin). 

Dosage and duration of therapy depend on patient response, tolerance of side effects, and development of retinal toxicity, which is a potentially irreversible adverse reaction associated with long-term therapy, especially with chloroquine. Current recommended doses of antimalarials in SLE are hydroxychloroquine 200-400 mg/day and chloroquine 250-500 mg/day. After 1 or 2 years of treatment, gradual tapering of dosage can be attempted. Some patients may require only one or two tablets per week to suppress cutaneous manifestations. ... 

Side effects of these drugs include CNS effects (e.g., headache, nervousness, insomnia, and others), rashes, dermatitis, pigmentary changes of the skin and hair, gastrointestinal disturbance (e.g., nausea), and reversible ocular toxicities such as cycloplegia and corneal deposits. Potentially serions retinal toxicity is uncommon when the currently recommended doses are used and is least common with hydroxychloroquine. However, because of the possibility of permanent damage associated with the retinopathy, an ophthalmologic evaluation should be done at baseline and every 3 months when chloroquine is used and every 6 to 12 months when hydroxychloroquine is used. If retinal abnormalities are noted, antimalarial therapy should be discontinued or the dose reduced. ... 

Talamo JH, D Amico DJ, Hanninen LA. The influence of aphakia and vitrectomy on experimental retinal toxicity of aminoglucoside antibiotics. Am J Ophthalmol 1985 100 840-847. 

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