Ординатура / Офтальмология / Английские материалы / Clinical Ocular Pharmacology 5th edition_Bartlett, Jaanus_2008

may exacerbate ciliary spasm and inflammation and may increase the likelihood of synechia. Prostaglandins are also avoided because this group of medications may exacerbate the inflammatory component.

Several treatment trials have provided guidance for the management of glaucoma, which are summarized in Table 34-9. In addition, several new studies are

under way that will likely provide information on questions that regularly confront clinicians. These include studies of glaucoma in African-Americans, the effects of corneal parameters on IOP, the comparison between imaging devices and the clinical assessment of the optic nerve, novel approaches to perimetry, and evaluations of new treatment options.

After 2 years of follow-up, more eyes were controlled by initial treatment with

ALT vs. timolol.

No significant differences between groups on visual acuity or visual fields.

ALT may be an alternative to medication as initial treatment.

Completed before prostaglandins, topical CAIs, or α agonists.

IOP is part of pathogenic process in NTG. Lowering IOP may be beneficial for patients with NTG.

A significant percentage of surgical patients developed visually significant cataracts.

Because 40% of untreated eyes showed no progression, the decision to treat aggressively must be weighed against the individual likelihood of progression.

Most patients who met these study criteria showed visual field progression during the length of the study.

Patients with IOP < 18 mm Hg for the entire duration of the study (average 12.3 mm Hg, over 6 years) had the most stable visual fields.

Suggests aggressive medical management from baseline IOP values is indicated in advanced glaucoma.

Vision better preserved if ALT first

(vs. trabeculectomy) in African-American patients (7-year follow-up).

Vision better preserved if trabeculectomy first in white patients (7-year follow-up).

Visual field loss was similar in both groups. Incidence of cataract removal was higher in

the surgery group.

Mean IOP was slightly lower with surgery (46% vs. 38%).

Visual acuity loss was greater with surgery in the short term but similar after 4 years.

Patients reported better comfort in medically managed group.

Aggressive medical treatment provides benefits comparable with those of trabeculectomy in the initial treatment of glaucoma.

PATIENT ADHERENCE TO MEDICATION AND FOLLOW-UP REGIMENS

The Nature of the Disease

There are many barriers to adherence in the treatment of glaucoma. Some are related to the inherent nature of the disease itself. Patients with the most common form of glaucoma (primary open-angle glaucoma) are generally asymptomatic, and the condition is diagnosed incidental to the patient’s chief complaint. Care should be taken to address the initial reason for the patient’s visit in addition to a new diagnosis. This may prevent the situation where a patient returns to the office to determine the efficacy of the initial treatment, only to find that he or she discontinued the medication because it did not address the entering complaint. This underscores the need for good doctor–patient communication.

Self-Medicating With Ophthalmic Medication

Unique to ophthalmic medical management, self-medicating with ophthalmic drops is a learned skill that does not come naturally. In fact, the natural defense systems of the eye (corneal reflex, blepharospasm) must be overcome to be successful. It is not uncommon, even for a patient who believes he or she is faring well, to complain that his or her 2.5-ml bottle of topical prostaglandin is lasting only

3 weeks.

Medication Costs

Ophthalmic medications are expensive. The costs of these drugs can be prohibitive for patients who do not have prescription drug coverage. Fortunately, most ophthalmic drug companies have patient assistance programs. These programs add a layer of office administration and must be regularly renewed, but they add great value to one’s glaucoma practice.

Insurance Companies

Effects on Quality of Life

Assuming that the patient understands he or she has glaucoma and that, in his or her case, it requires medical management, there will be obstacles associated with treatment that must be addressed.

Certain insurers have a preferred ophthalmic medication formulary. These select drugs typically represent the result of a negotiated price between a pharmaceutical company and an insurance provider. These costsaving measures are an integral part of the health care industry and serve to keep costs manageable for the

company and for the patient. Unfortunately, they can be a source of confusion and concern. When the practitioner recommends a certain medication, the choice was typically made by taking into account the unique needs of the individual patient.When this recommendation differs from the medications available in the patient’s formulary, the patient may express concern that he or she may not be receiving what is best. Although sometimes this actually is the case, it may also be a simple matter of brand preference on the part of the provider.

For patients who require a copayment for their medications, it is sometimes advantageous for them to receive a prescription written for a 90-day supply (e.g., 2.5 ml bottle × 3 vs. one 2.5-ml bottle refilled three times). A 3-month prescription may avoid the cost associated with each refill and, more importantly, reduces the chances of a patient missing doses between refills.

SELECTED BIBLIOGRAPHY

IOP

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Doughty MJ, Zaman ML. Human corneal thickness and its impact on intraocular pressure measures: a review and meta-analysis. Surv Ophthalmol 2000;44:367–408.

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Kirstein EM. Dynamic contour tonometry. Optometric Glaucoma Society E-Journal 2006;2(1).

Liu JH, Kripke DF, Hoffman RE, et al. Nocturnal elevation of intraocular pressure in young adults. Invest Ophthalmol Vis Sci 1998;39:2707–2712.

Liu JH, Kripke DF, Twa MD, et al. Twenty-four hour pattern of intraocular pressure in the aging population. Invest Ophthalmol Vis Sci 1999;40:2912–2917.

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GONIOSCOPY

Coleman AL, Yu F, Evans SJ. Use of gonioscopy in Medicare beneficiaries before glaucoma surgery. J Glaucoma 2006;15:486–493.

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STRUCTURAL

Bowd C. Structure-function relationships using confocal scanning laser ophthalmoscopy, optical coherence tomography, and scanning laser polarimetry. Invest Ophthalmol Vis Sci 2006;47:2889–2895.

Budenz DL. Detection and prognostic significance of optic disc hemorrhages during the ocular hypertension treatment study. Ophthalmology 2006;113:2137–2143.

Jonas JB, Martus P, Budde WM, Hayler J. Morphologic predictive factors for development of optic disc hemorrhages in glaucoma. Invest Ophthalmol Vis Sci 2002;43:2956–2961.

Jonas JB, et al. Ranking of optic disc variables for detection of glaucomatous optic nerve damage. Invest Ophthalmol Vis Sci 2000;41:1764–1773.

Kim SH, Park KH.The relationship between recurrent optic disc hemorrhage and glaucoma progression. Ophthalmology 2006;113:598–602.

Siegner SW, Netland PA. Optic disc hemorrhages and progression of glaucoma.Am J Ophthalmol 2000;129: 707–714.

Zangwill LM, Medeiros FA, Bowd C, Weinreb RN. Optic nerve imaging: recent advances. In: Grehn F, Stamper R, eds. Glaucoma. Berlin: Springer-Verlag, 2004: 63–91.

VISUAL FIELDS

Anderson RS. The psychophysics of glaucoma: improving the structure/function relationship. Prog Retin Eye Res 2005;25:79–97.

Artes PH, Hutchison DM, Nicolela MT, et al. Threshold and variability properties of matrix frequency-doubling technology and standard automated perimetry in glaucoma. Invest Ophthalmol Vis Sci 2005;46:2451–2457.

Budenz DL, Rhee P, Feuer WJ, et al. Comparison of glaucomatous visual field defects using standard full threshold and Swedish interactive threshold algorithms. Arch Ophthalmol 2002; 120:1136–1141.

Dacey DM, Lee BB.The “blue-on” opponent pathway in primate retina originates from a distinct bistratified ganglion cell type. Nature 1994;367:731–735.

Dacey DM, Packer OS. Colour coding in the primate retina: diverse cell types and cone-specific circuitry. Curr Opin Neurobiol 2003;13:421–427.

Frisen L. High-pass resolution perimetry: evidence for parvocellular neural channel dependence. Neuroophthalmology 1992;4:257–264.

Gupta N,Ang LC,Noel de Tilly L,et al. Human glaucoma and neural degeneration in intracranial optic nerve, lateral geniculate nucleus, and visual cortex. Br J Ophthalmol 2006;90:674–678.

Harwerth RS, Crawford ML, Frishman LJ, et al.Visual field defects and neural losses from experimental glaucoma. Prog Retin Eye Res 2002;21:91–125.

John L,Keltner JL.Normal visual field tests following glaucomatous visual field endpoints in the Ocular Hypertension Treatment Study (OHTS).Arch Ophthalmol 2005;123: 1201–1206.

Keltner JL, Johnson CA, Quigg JM, et al. Confirmation of visual field abnormalities in the Ocular Hypertension Treatment Study.Arch Ophthalmol 2000;118:1187–1194.

Sample PA. Identifying glaucomatous vision loss with visual- function-specific perimetry in the Diagnostic Innovations in Glaucoma Study. Invest Ophthalmol Vis Sci 2006:47: 3381–3389.

698 CHAPTER 34 The Glaucomas

Sample PA, Bosworth CF, Blumenthal EZ, et al. Visual functionspecific perimetry for indirect comparison of different ganglion cell populations in glaucoma. Invest Ophthalmol Vis Sci 2000;41:1783–1790.

Wyatt HJ, Dul MW, Swanson WH. Variability of visual field measurements is correlated with the gradient of visual sensitivity. Vision Res 2007;47:925–936.

Yucel YH, Zhang Q,Weinreb RN, et al. Effects of retinal ganglion cell loss on magno-, parvo-, koniocellular pathways in the lateral geniculate nucleus and visual cortex in glaucoma. Prog Retin Eye Res 2003;22:465–481.

TREATMENT

American Academy of Ophthalmology Glaucoma Panel. Preferred practice pattern. Primary open-angle glaucoma. Limited revision. San Francisco: American Academy of Ophthalmology, 2003.

Asrani S, Zeimer R,Wilensky J, et al. Large diurnal fluctuations in intraocular pressure are an independent risk factor in patients with glaucoma. J Glaucoma 2000;9:134–142.

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He M, Foster PJ, Johnson GI, Khaw PT. Angle-closure glaucoma in East Asian and European people. Different diseases? Eye 2006: 20(1):3-12.

Hoh ST,Aung T, Chew PT. Medical management of angle closure glaucoma. Semin Ophthalmol 2002;17:79–83.

Hughes E, Spry P, Diamond J. 24-Hour monitoring of intraocular pressure in glaucoma management: a retrospective review. J Glaucoma 2003;12:232–236.

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Liebmann JM, Ritch R. Laser surgery for angle closure glaucoma. Semin Ophthalmol 2002;17:84–91.

Piltz-Seymour J, Jampel H. The one-eye drug trial revisited. Ophthalmology 2004;111:419–420.

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Since the 1970s the effect of systemic drug therapies on ocular functions has received considerable attention.The dramatic increase in the number and diversity of drug therapies has necessitated the development of systematic mechanisms to identify the relative risk of adverse effects across populations. Although adverse drug reactions (ADRs) are identified in large clinical trials, often it is not until the drug is marketed and used by the public that the full picture of possible effects can be elucidated. When clinical observations are reported in significant numbers to central databases, these effects can be studied and possible causal connections between systemic drug use and ocular effects established. Because of their unique position in the health care system, primary eye care practitioners are often the first to see ADRs, in particular ocular ADRs (OADRs). The goal of early recognition and management strategies for OADRs can be complicated by numerous factors, such as multiple drug regimens, predisposing patient factors, and lack of conclusive evidence that the drug or drugs implicated are the cause of the observed reaction. Of course, an appropriate balance between the recognition, confirmation, and significance of an OADR against the physiologic need for the drug treatment in a given patient requires considerable understanding of the literature as well as collaboration with the patient and his or her team of health care professionals.

Drugs can cause direct ocular toxicity through the production of arachidonic acid derivatives, the liberation of free radicals, and the disruption of blood–aqueous and blood–retinal barriers. In addition, because of the rich blood supply and relatively small mass,the eye exhibits an unusually high susceptibility to toxic substances. Drug molecules present in systemic circulation can reach the ocular structures by way of both the uveal and retinal blood supplies. Lipophilic drugs are more able to penetrate ocular structures, including the blood–retinal barriers, at both the tight junctions of the retinal pigment epithelium (RPE) and the retinal capillary endothelium. Once in the eye, drugs and chemicals may deposit in ocular tissues. These structures, including the cornea, lens, and retina, may then act as drug reservoirs, trapping

and slowly releasing drug or enhancing the potential toxicity of the drug. Finally, the RPE is highly active metabolically and is critical in drug biotransformation via the cytochrome P-450 system, a system that is highly variable. This may further complicate the wide variation in drug effects noted between individuals, despite the attempt to control for similar dosing regimens and other clinical parameters.

Because the eye is highly accessible to clinical examination, drugs that cause a deposit or change to an ocular structure can be readily observed, often before there is any functional change noted by the patient.Thus, many systemically administered drugs can cause adverse ocular effects, nearly all structures of the eye are vulnerable, and eye care professionals must be vigilant to detect such changes.

Many reports of OADRs involve individual cases in which the administration of one or more drugs resulted in some unexpected sign or symptom. Practitioners are encouraged to report any suspected OADRs to one of a number of sources:the U.S.Food and Drug Administration’s Medwatch system (www.fda.gov/medwatch/index.html), the World Health Organization’s (WHO) spontaneous reporting database (www.who-umc.org), the National Registry of Drug-Induced Ocular Side Effects (www. eyedrugregistry.com), the Canadian Adverse Drug Reaction Information System (http://www.hc-sc.gc.ca/), and the Canadian Ophthalmological Society’s Canadian Ocular Drugs Reporting System (www.eyesite.ca). Although reports received may be imperfect, these postmarketing efforts by clinicians are considered to be critical “signals” to identify possible trends in OADRs that may not have been triggered by the initial clinical trials.

To attempt to deal with the incompleteness of data in these case-based reports, the WHO developed a classification system for these adverse events (Table 35-1). This involves identifying a temporal association with the use of the drug and the OADR, a dose–response relationship, both positive dechallenge and positive rechallenge corroboration for the effect, and a plausible scientific explanation of the effect, including similar responses being noted with other drugs in the same class. Rarely is

the patient rechallenged with the implicated drug so that absolute causation of an adverse event is difficult to determine; however, collectively, these isolated observations may represent significant findings and warrant further study.The WHO’s Causality Assessment Guide is useful not only to categorize ADRs with the drug but as a guide to clinicians in counseling patients and identifying problems.

This chapter considers primarily those prescription drugs that have been frequently implicated in OADRs. Some of the common OADRs noted in vitamin and herbal supplements are listed toward the end of the chapter. Clinically important drug effects are categorized in the ocular structure or function affected rather than in specific drug classes. A comprehensive review chart at the end of the chapter serves as a reference and study guide (Appendix 35-1). Recommendations for eye care practitioners for reporting suspected drug-induced ocular adverse effects are reviewed.

DETERMINANTS OF ADVERSE

DRUG REACTIONS

Amount of Drug Administered

Nearly every drug, if administered in excessive amounts, may produce toxic effects.Toxic levels of drugs can result even when daily doses are in the normal therapeutic ranges if administration is prolonged or when other drugs potentiate the effects or when drug detoxification or excretion mechanisms operate more slowly than expected. The effect of excessive drug intake has been observed

with several drugs and is particularly well documented with chloroquine. When it is used as a malaria suppressant, ocular complications are rare. In control of chronic rheumatoid arthritis and systemic lupus erythematosus, however, relatively large dosages of chloroquine had been administered, and irreversible ocular complications involving the retina were determined to be a “certain” adverse effect of the drug.

Nature of the Drug

The inherent pharmacologic properties of a drug determine its pharmacodynamic effects, and drug absorption, distribution, metabolism, and excretion are determined by the pharmacokinetic effects. The ease with which a drug passes into the systemic circulation and its ability to penetrate the blood–brain, blood–aqueous, or blood– retinal barriers determines the propensity to affect ocular tissues and functions.

The binding of drugs to melanin can lead to ocular toxicity.The free-radical nature of melanin, which is present in ocular structures such as the uveal tract and RPE, may contribute to the binding ability of certain drugs, including psychotropic agents such as chlorpromazine. Drugs can bind to ocular structures other than melanin. Digitalis accumulates in the retina and ciliary body. Other drugs may produce OADRs by their systemic pharmacologic activity. For example, subconjunctival or retinal hemorrhages can be caused by use of anticoagulants such as heparin or aspirin and with the use of hormone replacement therapy or oral contraceptives.

Route of Administration

All routes of drug administration can affect ocular structures and functions. OADRs have been associated with topical ophthalmic administrations as well as local injections. Systemically, oral drug administration has been implicated most frequently in the development of OADRs. However, parenteral as well as inhaled or nasally applied drugs have also produced OADRs. Topical application to the skin, particularly if it is abraded or burned, may result in sufficient systemic absorption to lead to ocular side effects. Dermatologic use of antibiotics has resulted in ocular hypersensitivity reactions.

Pathophysiologic Variables

The presence of systemic disease can alter the way an individual detoxifies or excretes a drug. Liver and kidney disease, in particular, can markedly influence drug response by allowing the drug to accumulate to toxic levels. The rate of excretion of digoxin, for example, is reduced considerably in patients with renal impairment, thus causing an increased risk of alterations in color vision in these patients.

Age and Gender

Because ADRs are more likely to occur in the very young and the elderly, lower drug dosages may be indicated at these two extremes of the human life span. The elderly are more likely to have diseases such as cancer, coronary heart disease, dementia, diabetes mellitus, hypertension, and osteoporosis and may also have adverse nutritional reactions. Deficiencies in liver and kidney function can result in marked delay of drug detoxification and elimination. Constant review of established diagnoses and treatments is important to minimize the number of drugs administered,and care must be taken to determine whether other nutritional supplements and herbal products are being incorporated into self-treatment.

In general, more adverse systemic drug reactions are reported in women than in men, although it is not clear whether this also applies to OADRs. Among the factors that may explain these gender differences are pharmacokinetic differences, including body size; the impact of hormonal changes; and the use of oral contraceptives and other medications used selectively or primarily by women.

Multiple Drug Therapies,

Recreational Drugs, Herbal

Supplements, and Nutrition

In general, the incidence of ADRs increases with the number of drugs administered. Interactions can occur when a drug is added to, or withdrawn from, a therapeutic regimen. Dietary supplementation occurs in over half of

the U.S. population, whereas only half of these patients report the use of additional agents to their physicians. With the increase in the number of vitamins and herbal products being introduced to the market and being consumed by the general population, ADRs are presumed to be both increasingly numerous and more difficult to isolate to a particular agent. Social habits, including alcohol, recreational drug use, and smoking, should also be considered.

Many different sites or mechanisms can be involved. For example, an addition of an agent, be it a drug, herbal, or nutritional supplement, can alter the absorption, distribution, biotransformation, or excretion of other drugs. In addition, a drug may alter the sensitivity of certain tissues to other drugs or act at the same cellular site or on the same physiologic system. Other factors, such as drug incompatibility, can lead to inactivation and loss of pharmacologic activity.

History of Allergy to Drugs

Adverse reactions to drugs are more likely to occur in patients with a history of previous reactions. For a drug to cause an allergic reaction,it must combine with an endogenous protein and form an antigenic complex. Subsequent exposure of the patient to the drug or an agent similar to it results in an antigen–antibody interaction that invokes the allergic response. Such reactions are not usually dose related, and relatively small quantities of drugs that act as allergens can provoke a significant reaction.

Allergic reactions are not infrequent and, more often than not, are unpredictable and sometimes difficult to manage. The skin is the most commonly involved tissue. Reactions can range from a mild rash to exfoliative dermatitis and erythema multiforme. Ocular structures most commonly affected are the eyelids and the conjunctiva.

Numerous systemic drugs have been implicated, including the penicillins and sulfonamides, which can cause swelling of the lids and conjunctiva as part of a generalized urticaria or localized angioneurotic edema. Other drugs implicated in ocular allergic reactions are antidepressants, antipsychotics, antihypertensives, antirheumatics, sedatives, and hypnotics.

Individual Idiosyncrasy

Idiosyncrasy refers to an unexpected reaction that can occur in some patients after administration of a drug. These qualitatively abnormal responses have been attributed to heritable characteristics that result in altered handling of or abnormal tissue responsiveness to drugs.

Alterations in enzymatic mechanisms could be responsible for some observed toxicities.Thus, the drug itself or metabolites formed in the liver or other organs of the body could enter the eye. It is also possible for metabolites

isolated from various ocular tissues, including the corneal epithelium, iris, ciliary body, and RPE.

DIAGNOSIS AND MANAGEMENT

OF OADRs DUE TO SYSTEMIC DRUGS

An effective approach to the diagnosis of OADRs is to take a detailed drug history that includes over-the-counter drugs, nutritional and herbal medications, prescription agents, and recreational and social substances.A temporal relationship between drug use and ocular signs or symptoms is one of the first clues to diagnosis.“Dechallenge” refers to removal of the drug with concomitant elimination of the OADR.“Rechallenge” refers to the return of the effect on reintroduction of the drug.The practitioner must be familiar with the possible ocular effects of all agents that patients may be taking and be prepared to research the literature for new reports and management strategies. Detailed data should be gathered from each patient, and the practitioner should consider reporting the OADRs to an appropriate drug registry.

When used in normal therapeutic doses, most drugs have a relatively low incidence of drug-induced ocular complications. Many drugs, however, can cause adverse effects, whereas others may cause changes to ocular tissues or visual functioning when taken in excess.

Table 35-2

Drugs That Can Affect the Cornea and Crystalline Lens

The following sections consider the most important drugs that have the potential to affect the eye. Where possible, the WHO Classification for Causality is listed for each sign or symptom. Where available, a brief explanation of the etiology is provided and the management strategy for the OADR is discussed.

DRUGS AFFECTING THE CORNEA AND CRYSTALLINE LENS

Systemic drugs and their metabolites may reach the cornea and lens via the tear film, limbal vasculature, and also the aqueous humor. Deposition may occur, as can direct toxicity to the structures of the cornea and lens. Although corneal opacities secondary to drug therapies are often irreversible with drug cessation or reduction, these opacities may signal more permanent deposits of drug in the lens and, possibly more importantly, the retina.

Many drugs have been associated with corneal and crystalline lens opacities, including phenothiazines, allopurinol, phenytoin, diuretics, and heavy alcohol consumption. Over 16 drugs are listed to be associated with epithelial vortex keratopathy alone in a recent review, whereas the stroma is affected much less frequently. A variety of ocular toxicities are well recognized, aside from isolated case reports, and the drugs responsible for these side effects are listed in Table 35-2.

Corticosteroids

Natural and synthetic steroids are used extensively to treat arthritis and other rheumatoid diseases, including rheumatic heart disease.They are also used in some cases of autoimmune diseases such as systemic lupus erythematosus, severe asthma and in some respiratory diseases, and in some ocular allergy and inflammatory conditions. Steroids can be administered orally, intravenously, or intranasally or be inhaled.

Clinical Signs and Symptoms

The ocular side effects of corticosteroids are many and are related to the route of administration. The most common concerns are increased intraocular pressure (IOP) and cataracts, but delayed epithelial wound healing and increased risk of infection due to immune modulation and decreased tear lysozyme levels are issues for the cornea. Changes to other ocular tissues have been noted (subconjunctival hemorrhages, blue sclera, eyelid hyperemia and edema, retinal embolic events, central serous choroidopathy) and neurologic complications reported (diplopia, nerve palsies, intracranial hypertension) (see Appendix 35-1).

The association between steroid use and cataracts has been well known since the early 1960s. Visual impairment is uncommon, though patients may report light sensitivity, photophobia, reading difficulty, or glare.

The use of systemic,topical ophthalmic,topical dermatologic, and nasal aerosol or inhalation steroids has been implicated as causing posterior subcapsular (PSC) cataracts that are clinically indistinguishable from other causes, including age-related PSC cataracts. PSC cataract formation is irreversible and is likely dose dependent.The usual time of onset to cataract formation is 1 year with a dosage of 10 mg/day of prednisone, although it has been seen after as little as 5 mg/day for as short as 2 months. The range of incidence of (oral) corticosteroid-related cataract is 6.4% to 38.7%. A strong association has been found between the use of inhaled steroids and PSC cataracts,but no clear association has been noted between intranasal steroids and the development of PSC cataracts. Because of considerable variation in the numbers of patients studied, dosage and duration of treatment, criteria for diagnosis, route of drug administration, and the underlying disease process itself, attention has focused on the possibility that PSC cataract formation may be related more to factors of individual susceptibility than to drugrelated factors. Hispanics appear to be more predisposed to steroid-induced PSC cataracts than are either whites or blacks. It was thought that children were more susceptible than adults, developing PSC cataracts at a lower dosage and in a shorter time; however,this may have been due to the relatively large doses of steroids used in relation to low body weight and is not seen in contemporary treatment of children, except in children in whom frequent courses of systemic steroids are used.

Etiology

The pathogenesis of steroid-induced cataract is likely multifactorial, including bonding of certain chemicals, water accumulation,protein agglutination,and various biochemical consequences of abnormal glucose metabolism.

Management

The short-term use of systemic steroids is not associated with a significant risk of cataract. Patients who take long-term oral or inhaled steroids, however, should have careful slit-lamp examinations performed through a dilated pupil every 6 to 12 months. Although the longterm administration of inhaled steroids is relatively safe compared with the long-term use of oral steroids, prolonged use of high dosages of inhaled steroids increases the risk of PSC and nuclear cataracts. Because it is possible for patients to develop cataracts even when taking very low dosages of steroid, every patient, regardless of dosage or route of administration, should be evaluated carefully for the presence of drug-induced cataract. When drug-induced cataracts are discovered, the prescribing practitioner should be notified. Normally, because of the ADR profile of systemic steroids, care has already been taken to taper the patient to the lowest tolerable dosage required to control his or her inflammation. However, consideration may be given to attempt to further reduce the dosage in light of the OADR.There is generally no increased risk to the patient having cataract extraction secondary to steroid-induced PSC cataracts.

Chloroquine and Hydroxychloroquine

Chloroquine and hydroxychloroquine are quinoline drugs used for the chronic management of rheumatoid arthritis, discoid and systemic lupus erythematosus, and other collagen diseases. Because chloroquine is rapidly absorbed and becomes highly concentrated in various tissues due to melanin and protein binding, it is now used only for malaria prophylaxis. Hydroxychloroquine has replaced it primarily because of its superior safety profile.

Clinical Signs and Symptoms

The pattern of hydroxychloroquine and chloroquine keratopathy can be divided into three stages of severity. In the early stages, fine diffuse deposits appear in the corneal epithelium. Later, the deposits aggregate into curved lines that converge and coalesce just below the central cornea. Finally, green-yellow pigment spots appear as concentric lines in a “whorl-like” opacity. Corneal deposits can be observed as early as 2 to 6 weeks after beginning therapy, and there is no relationship between the development of corneal deposits and the occurrence of retinopathy, the more significant OADR of these drugs.

Keratopathy is rare in patients taking hydroxychloroquine (1% to 28%) versus up to 95% of those who took chloroquine. Though studies have found no correlation