Toxic keratitis

Anaphylactoid keratitis Allergic contact keratitis Irritative or toxic keratitis Phototoxic keratitis Toxic calcific band keratopathy Pseudotrachoma Cumulative deposition Microbial imbalance... 

Toxic keratitis has also been reported after abuse of cyclopentolate. Instillation of 100 to 400 drops of the 1% solution over several months caused a diffuse epithelial punctate keratitis with marked conjunctival hyperemia. As expected, the pupils were widely dilated and unresponsive to light. 

A wide range of substances that are toxic to the cornea may produce epithelial insult known as toxic keratitis. This terminology is generally reserved for mild superficial corneal irritation after contact with a harmful substance. Solutions foreign to the eye that commonly cause toxic keratitis include shampoos, lotions, and chlorinated pool water. Toxic corneal reactions have been reported from tonometer tips contaminated with 70% isopropyl alcohol or hydrogen peroxide that was not fully removed after disinfection of the probe. Irreversible corneal scarring has resulted from inadvertent ocular contamination with chlorhexidine gluconate, a skin cleanser used preop-eratively. The mistaken use of nonophthalmic products for eyedrops may result in various forms of corneal trauma. 

The patient with toxic keratitis or medicamentosa generally reports recent exposure to the offending substance or the use of an ophthalmic preparation on a short- or long-term basis. In the case of mild toxic keratitis, the patient may have few or no symptoms. More involved cases may produce very definite symptoms of redness, irritation, burning, tearing, and ocular discomfort upon instillation. 

Figure 26-38 Diffuse punctate epithelial erosions in a patient with toxic keratitis. (Courtesy of Pat Caroline.)...

In the case of mild transient toxic keratitis, patient comfort may be enhanced with the use of topical nonpre-served lubricating agents while the condition resolves. In the case of more pronounced toxic keratitis, particularly with conjimctival injection, topical decongestant agents... 

More severe forms of toxic keratitis may require prophylactic antibiotic therapy to protect the inflamed cornea. The use of topical aminoglycosides should be avoided, however, as they tend to exacerbate the condi-tion.The use of a mild steroid, such as 0.12% prednisolone drops four times a day, aids the resolution of more advanced cases. Any allergic component involving the eyelids or conjunctiva should be treated appropriately. 

If topical anesthetic abuse is suspected, discontinuation is critical. A broad-spectrum topical antibiotic such as 0.5% moxifloxacin three times daily is used to protect the disrupted corneal epithelium from secondary infection as the tissue heals. Topical NSAIDs, such as 0.1% diclofenac sodium solution or 0.5% ketorolac solution, and a therapeutic soft contact lens help to reduce pain. Cycloplegic and topical steroids are indicated if an anterior chamber reaction is present.Toxic keratitis can heal without permanent vision loss within days after discontinuing the use of the anesthetic but may result in permanent scarring, vascularization, and visual loss. Surgical treatment, such as a penetrating keratoplasty, may be necessary. 

Wasserman BN, Liss RP, Santander SH. Recurrent corneal ulceration as late compUcation of toxic keratitis. Br J Ophthalmol... 

Abuse of these medications often results in irreversible corneal damage and visual loss (330). Two patients continued to instil their topical 0.5% tetracaine eye-drops, despite medical advice. The result was bilateral corneal perforation in the first case and a large unilateral desce-metocele in the second. Surgery was required to correct the perforations, but the long-term anatomical and functional results were poor. A third patient had obtained 0.5% tetracaine hydrochloride drops over the counter to relieve discomfort in his eye after colleagues at work had attempted to remove a foreign body from his eye. He had developed chronic toxic keratitis and was persuaded to discontinue the eye-drops. With appropriate treatment the cornea returned to normal. 

Trifluridine, C2qH22F2N20, (5-trifluoromethyl-2 -deoxyuridine [70-00-8] F TdU, 14) was first prepared (30) in 1962. It is used for topical therapy of herpes vims-infected eyes. It is especially usefiil for treating infections that are resistant to IdU therapy. Like IdU, trifluridine is incorporated into DNA in place of thymidine in both infected and uninfected cells. But it is 10 times more potent than IdU against herpes keratitis in rabbits and 10 times more soluble in water. Trifluridine is also usefiil in treating human cytomegalovims (HCMV), but its toxicity to bone marrow may limit its clinical use. 

Cyanide toxicity was tested in rabbits by applying 1.69-5.28 mg CNVkg/day as sodium cyanide to the inferior conjunctival sac of one eye (Ballantyne 1983b, 1988). Irritation, lacrimation, and conjunctival hyperemia were present immediately after the treatment. Keratitis developed in some rabbits after a cyanide application of 0.9 mg CNTkg as hydrogen cyanide, 2.1 mg CNTkg as sodium cyanide, and 2.5 mg CN /kg as potassium cyanide. 

Epithelial keratitis that has not responded clinically to topical idoxuridine, or when ocular toxicity or hypersensitivity to idoxuridine has occurred. In a smaller number of patients resistant to topical vidarabine, trifluridine was also effective. 

Nitisinone is a reversibile inhibitor of 4-hydroxy-phenylpyruvate oxidase, an enzyme that plays a crucial role in the tyrosine catabolic pathway. Nitisinone prevents the accumulation of the toxic metabolites fumaryl acetoacetate, succinyl acetoacetate and succinyl acetone. Nitisinone is used for the treatment of hereditary tyrosinemia type 1. After oral administration bioavailability is 90% and peak levels are reached at 2.5 hours after dosing. The drug is eliminated mainly in the urine but some CYP3A4-mediated metabolism seems to occur. The elimination half-life is 45 hours. Blood dyscrasias are frequently occurring side effects as are eye problems like conjunctivitis, corneal opacity and keratitis. Exfoliative dermatitis, erythematous rash and pruritus... 

Local or topical administration of amphotericin has been used with success. Mycotic corneal ulcers and keratitis can be cured with topical drops as well as by direct subconjunctival injection. Fungal arthritis has been treated with adjunctive local injection directly into the joint. Candiduria responds to bladder irrigation with amphotericin B, and this route has been shown to produce no significant systemic toxicity. 

Research in antiviral chemotherapy began in the early 1950s, when the search for anticancer drugs generated several new compounds capable of inhibiting viral DNA synthesis. The two first-generation antivirals, 5-iododeoxyuridine and trifluorothymidine, had poor specificity (ie, they inhibited host cellular as well as viral DNA) that rendered them too toxic for systemic use. However, both are effective when used topically for the treatment of herpes keratitis. 

Vidarabine [vye DARE a been] arabinofuranosyl adenine, ara-A, adenine arabinoside) is one of the most effective of the nucleoside analogs and is also the least toxic. However, it has been supplanted clinically by acyclovir, which is more efficacious and safe. Although vidarabine is active against herpes simplex virus type 1 (HSV-1), HSV-2, and varicella-zoster virus (VZV), its use is limited to treatment of immunocompromised patients with herpes simplex keratitis or encephalitis, or VZV infections. Vidarabine, an adenosine analog, is converted in the cell to its 5 -triphosphate analog (ara-ATP), which is postulated to inhibit viral DNA synthesis. Some resistant herpes virus... 

In addition to the acute toxic effects on the eyes, skin, and respiratory tract, both acute and longer-term neuropsychiatric effects (e.g. depression, anxiety, neurasthenia, insomnia, post-traumatic stress syndrome) have been documented for individuals exposed to sulfur mustard (Romano et al, 2008). Many of these effects have been documented for individuals exposed during noncombat (e.g. munitions plant workers) activities and are not always the result of high-level exposure that result in serious overt effects. Longer-term effects such as chronic bronchitis have been associated with occupational exposures that included episodes of acute toxicity, and delayed or recurrent keratitis may occur 8-40 years after a severe vapor exposure. Sulfur mustard-induced immunosuppression resulting in greater susceptibility to infections has also been reported. 

In studies involving human exposure (Rengstorff and Mershon, 1969a, b), CS (0.1% or 0.25% in water 1.0% in triocyl phosphate) sprayed or administered as ophthalmic drops onto the eyes, caused apraxia of eyelid opening with blepharospasm upon eyelid closure for 10 to 135 s. It also caused a transient conjunctivitis but no comeal damage upon further inspection with a slit lamp. Rabbit eyes contaminated with CS as a solution (0.5-10% in polyethylene glycol), as a solid, or thermally dispersed as a smoke (15 min at 6,000 mg/m ) showed a greater toxicity with solution. CS in solution caused profuse lacrimation, conjunctivitis, iritis, chemosis, keratitis, and corneal vascularization at concentrations at or above 1%. 

Higginbottom and Suschitzky (1962), the chemists who discovered CR, first noted the intense lacrimal response to this compound. A splash of CR (0.01 to 0.1% range solution) causes immediate ophthalmodynia, lacrimation, and blepharospasm, similar to CS and CN (Sidell, 1997). These effects can last 15 to 30 min before subsiding. Blepharitis (edema of the eyelids), periorbital edema, and injected conjunctivae can last for up to 6 h. In rabbits and monkeys, CR (0.1% solution) causes mild, transient erythema, che-mosis, and keratitis in the eye. Moderate conjunctivitis has been demonstrated with higher CR concentrations (5% solution) applied directly to the rabbit eye (Rengstorff et al, 1975). Ballantyne et al (1975) showed that increasing CR concentrations as a solution caused dose-dependent corneal thickening but minor eye effects (mild conjunctivitis and lacrimation) as an aerosol. In animal studies, the effects of CR on the eye are very transient as they are cleared in 1 h, and it produces far less toxicity to the eye than CN (Salem et al, 2006). 

Abuse of topically administered drugs by practitioners or patients can cause significant ocular toxicity. Infiltrative keratitis has occurred from long-term use of anesthetic eyedrops for relief of pain associated with corneal abrasions. Bilateral posterior subcapsular cataracts have developed after the topical administration of prednisolone acetate 0.12% twice daily over long durations. Practitioners should closely monitor patients treated with drugs known to have potentially significant ocular or systemic side effects. 

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