Cornea
Vortex keratopathy (cornea verticillata)
Clinical features
In approximately chronological order:
- •
Fine golden-brown opacities form an irregular horizontal line in the lower corneal epithelium of both eyes, similar to that of the common age-related Hudson–Stähli iron line.
- •
Several irregular branching horizontal lines form a pattern resembling the whiskers of a cat.
- •
With an increasing number of branches a whorled pattern develops, centred on a point below the pupil and swirling outwards, usually sparing the limbus.
- •
Associated pigmented clumps and iron deposition have been described.
Causes
- •
Amiodarone
- ○
Amiodarone is a cardiac antiarrhythmic agent.
- ○
Virtually all patients develop keratopathy ( Fig. 20.1A ), often soon after commencement. In general, the higher the dose and the greater the duration of use the more substantial the corneal changes.
Fig. 20.1
Drug-induced keratopathies. (A) Amiodarone-induced vortex; (B) chlorpromazine; (C) argyrosis; (D) chrysiasis
(Courtesy of L Zografos – fig. C)
- ○
Vision is minimally impaired in around 5%, with loss of a single line of Snellen acuity, mild blurring and haloes, though rarely are these sufficient for discontinuation of the drug. The keratopathy reverses (slowly) on discontinuation.
- ○
Amiodarone can also cause anterior subcapsular lens deposits and optic neuropathy (see below).
- ○
- •
Antimalarials
- ○
Chloroquine and hydroxychloroquine are quinolones used in the treatment of certain autoimmune connective tissue diseases and in the prophylaxis and treatment of malaria.
- ○
In contrast to chloroquine retinopathy (see below), keratopathy bears no relationship to dosage or duration of treatment. The changes are usually reversible on cessation of therapy, and sometimes clear despite continued administration.
- ○
- •
Others. Numerous other drugs have been reported as occasional causes of vortex keratopathy.
- •
Fabry disease.
Chlorpromazine
Chlorpromazine is used as a sedative and to treat psychotic mental illness. Some patients on long-term therapy may develop subtle diffuse yellowish-brown granular deposits in the corneal endothelium, Descemet membrane and deep stroma ( Fig. 20.1B ) within the palpebral fissure area. Anterior lens capsule deposits and retinopathy may also occur (see below).
Argyrosis
Argyrosis is a discoloration of ocular tissues secondary to silver deposits, and may be iatrogenic or from occupational exposure. Keratopathy is characterized by greyish-brown granular deposits in Descemet membrane ( Fig. 20.1C ). The conjunctiva may also be affected.
Chrysiasis
Chrysotherapy is the therapeutic administration of gold, usually in the treatment of rheumatoid arthritis. Chrysiasis is the deposition of gold in living tissue, and typically occurs only after prolonged administration. Virtually all patients who have received a total dose of gold compound exceeding 1500 mg develop corneal deposits, characterized by dust-like or glittering purple granules scattered throughout the epithelium and stroma, concentrated in the deep layers and the periphery ( Fig. 20.1D ). The findings are innocuous and are not an indication for cessation of therapy. In some cases the deposits clear after stopping treatment whilst in others they may persist. Other toxic effects of gold are innocuous lens deposits and, occasionally, marginal keratitis.
Amantadine
Amantadine is an oral agent used in the treatment of Parkinson disease and related conditions. Some patients develop diffuse white punctate opacities that may be associated with epithelial oedema, 1–2 weeks after commencement of the drug, which resolve with discontinuation.
Ciliary Effusion
Topiramate
Topiramate is an anticonvulsant also used in the treatment of migraine. It can cause acute angle-closure glaucoma with associated myopia due to ciliochoroidal effusion. A similar phenomenon has been reported with other drugs, especially other sulfonamides including acetazolamide.
- •
Presentation is usually within a month of starting treatment, with blurred vision, and sometimes haloes, ocular pain and redness.
- •
Signs include shallowing of the anterior chamber and raised intraocular pressure.
- •
Treatment consists of reducing the intraocular pressure and stopping the drug.
- •
Prognosis is usually good provided the complication is recognized.
Lens
Steroids
Both systemic and topical steroids are cataractogenic; resultant opacities are initially posterior subcapsular ( Fig. 20.2A ), with subsequent anterior subcapsular involvement. Individual liability seems to vary; children may be more susceptible than adults. The relationship between dose and duration and cataract formation is unclear, though higher doses and length of treatment are associated with greater risk. Early opacities may regress if steroids are discontinued, though sometimes progression may occur despite withdrawal.
Other drugs
- •
Chlorpromazine may cause the deposition of innocuous, fine, stellate, yellowish-brown granules on the anterior lens capsule within the pupillary area ( Fig. 20.2B ) in 50% of patients who have received a cumulative dose of 1000 g. The deposits persist despite discontinuation.
- •
Gold (see ‘ Cornea ’ above) causes innocuous anterior capsular deposits in about 50% of patients on treatment for longer than 3 years.
- •
Allopurinol , used in the treatment of gout, increases the risk of cataract formation in elderly patients with a high cumulative dose or extended treatment duration.
Uveitis
Rifabutin
Rifabutin is used mainly in the management and prophylaxis of mycobacterial infections. It may cause acute anterior uveitis (AAU), typically associated with a hypopyon; associated vitritis may be mistaken for endophthalmitis. Concomitant use of drugs such as clarithromycin and fluconazole that inhibit the metabolism of rifabutin will increase the risk of uveitis. Treatment involves dose reduction or withdrawal of the drug.
Cidofovir
Cidofovir is used in the management of cytomegalovirus (CMV) retinitis in acquired immunodeficiency syndrome (AIDS). AAU with few cells but marked fibrinous exudate may develop following repeated intravenous infusions. Vitritis is common and hypopyon may occur with long-term administration. Treatment with topical steroids and mydriatics is usually successful, obviating the need to discontinue therapy.
Bisphosphonates
Bisphosphonates are a class of drugs that retard absorption of bone, commonly in osteoporosis but also in several other conditions. They activate certain T cells, and it is thought that uveitis (usually anterior) and scleritis sometimes seen following administration is related to this. Inflammation typically occurs within two days of commencement of a bisphosphonate, or earlier after intravenous administration.
Sulfonamides
Uveitis has been reported associated with sulfonamide treatment, but is rare. Sulfonamides can also precipitate ciliary effusion with myopia and angle closure (see above) and are a well-documented cause of Stevens–Johnson syndrome.
Fluoroquinolones
Systemic administration of fluoroquinolone antibiotics, particularly moxifloxacin, has been associated with acute extensive anterior segment pigment dispersal (see also bilateral acute iris transillumination (BAIT) and bilateral acute depigmentation of the iris (BADI) in Ch. 10 ). It is not clear whether inflammation is the primary mechanism, which may be phototoxicity due to sensitization by the drug in predisposed individuals.
Tumour necrosis factor inhibitors
Although these drugs (e.g. etanercept, infliximab, adalimumab) have been adopted for the treatment of ocular inflammation, paradoxically uveitis has also been documented as an adverse effect. The induction of sarcoidosis has also been reported.
Retina
Antimalarials
Introduction
Antimalarials are melanotropic: they are concentrated in melanin-containing structures of the eye, such as the retinal pigment epithelium (RPE) and choroid. Irreversible retinal toxicity develops in a small proportion of patients taking the drug; progression can occur subsequently despite discontinuation of the drug. It is now considered that retinal adverse effects may be more common than previously believed. Significant damage can occur without signs on fundus examination, so ancillary testing is a key part of assessment. In theory, hepatic or renal impairment might increase the risk of toxicity. Obesity may lead to miscalculation of the safe dose, as hydroxychloroquine is not stored in fat. Corneal signs are discussed above.
- •
Chloroquine is now much less commonly used given the availability of safer and more effective drugs. Retinal toxicity is related to cumulative dose, the risk of toxicity increasing significantly when the cumulative dose exceeds 300 g. Individual susceptibility seems highly variable, however.
- •
Hydroxychloroquine is much safer than chloroquine. The risk of retinal toxicity is considerably more marked (over 1%) with a cumulative dose over 1000 g, equating to a standard twice-daily dose of 200 mg for around seven years. Fewer than 20 cases have been documented with doses less than 6.5 mg/kg/day, and in none of these had there been less than five years of treatment.
Diagnosis
- •
Premaculopathy consists of early functional and structural changes prior to visible fundus signs; the goal of screening is to detect toxicity at this stage prior to irreversible damage.
- ○
Higher-resolution optical coherence tomography (OCT) imaging can show loss of the inner-segment/outer-segment junctional line ( Fig. 20.3A ) as an early feature, and is relatively sensitive.
- ○
