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Therapy of ocular fungal infections represents a challenge for the ophthalmic clinician. Although ocular fungal infections are relatively uncommon in developed countries compared with bacterial infections, the need for improved antifungal therapy is emphasized by the potentially poor clinical outcomes in patients with severe ocular mycoses. An increased number of fungal infections of the eye have been reported in the past few decades, in part, because of increased clinical awareness and improved laboratory techniques. The increase reflects more significantly the widespread use of antibiotics, immunosuppression, chemotherapy, and ocular prosthetic devices. Although the number of cases of ocular mycoses have increased, the number of antifungal agents available for therapy are few, given the number of fungal pathogens capable of infecting the eye. Current treatment for systemic fungal infections is not always sufficiently effective for ocular mycoses. The slower research and development progress in antifungal therapy compared with antibacterial therapy stems from the fact that fungal cells, unlike bacteria, are eukaryotic, so any drug that is toxic to fungal cells could potentially exert similar effects on mammalian cells. There also has been less financial incentive for pharmaceutical companies to invest in the development of ocular antifungal agents. Fungal infections can involve various regions of the eye and periocular tissues, including the lacrimal apparatus, conjunctiva, eyelids, and bony orbit. The two most common sites for fungal infections of the eye are the cornea and retina or vitreous. Successful medical treatment of fungal keratitis and endophthalmitis depends not only on the spectrum of antifungal activity of the particular drug but also on the pharmacokinetic properties of the agent (i.e., its ability to achieve therapeutic concentrations in the cornea or vitreous). This article reviews the antifungal agents currently available and under development for use in therapy of ocular fungal infections.

Herpes simplex virus (HSV) eye infections are a major cause of corneal opacity and visual loss in developed countries. The main goals of the treatment of HSV keratitis are: 1To eradicate the live virus 2To promote healing of corneal tissues 3To minimize the scarring resulting from the associated inflammation To decrease the chance for future recurrence The successful management of HSV keratitis depends on clinical recognition of the specific tissue layers involved and the various immune components of the keratitis. Modulation of HSV ocular disease relies upon the appropriate application of antiviral and anti-inflammatory medications.

Varicella-zoster virus (VZV) belongs to the Alphaherpesvirus subfamily along with herpes simplex virus types 1 and 2. The VZV virion consists of a double-stranded DNA core, icosahedral nucleocapsid and a glycoprotein-containing tegument. The tegument is enclosed in a lipid envelope composed of host cell membranes and viral glycoproteins. 2 Only enveloped virions are infectious. Glycoproteins are one of the most important antigens responsible for eliciting both humoral and cell-mediated immunity. Varicella-zoster virus is the causal agent of varicella (chickenpox) and herpes zoster (shingles). The common origin of these two diseases was first suggested in 1892 by Bokay, 119 who reported chickenpox in people exposed to herpes zoster patients, and later confirmed by Kundratitz, 60 who inoculated healthy children with herpes zoster vesicle fluid, causing a chickenpox outbreak. Subsequent studies proved viruses of chickenpox and zoster to be morphologically and histologically identical. 109,124

Parasitic infection of the retina has recently attracted more attention because of an increase in clinical cases occurring in AIDS patients. Recent developments in molecular microbiology have enabled more definitive diagnosis of these retinal parasites in many cases. In this article, a review of the most frequent parasitic infections involving the posterior segment is provided. A summary of retinal parasitic infections and associated systemic diseases is given in Table 1. The suggested therapy of choice is summarized as an outline in Table 2 for quick reference. This review includes a detailed discussion of the different therapeutic strategies and a recent update on medical and surgical methodology.

Efforts to improve the overall quality and efficiency of medical care within limited budgets are ongoing across all medical specialties, including ocular infectious disease. As part of this movement, decision makers are requesting data regarding the value of medical treatments increasingly, in addition to traditional measures of efficacy and safety. The demand for value data within medical care has spurred the growth of outcomes research that is focused on the final end points of treatments, as opposed to intermediate end points, surrogate markers, or the structure and process of providing medical care. Value is a multidimensional concept that requires simultaneous assessment and balancing of many factors affecting the costs and benefits of a treatment. A model illustrating a decision-making structure for conducting multidimensional value assessments for medical interventions has been proposed by Kozma and colleagues. 6 The model includes three types of outcomes of medical care: economic, clinical, and humanistic outcomes (ECHO). Examples of variables within each outcome category are presented below.* *Adapted from Kozma CM, Reeder CE, Schulz RM: Economic, clinical, and humanistic outcomes: A planning model for pharmacoeconomic research. Clin Ther 15:1121–1132, 1993; with permission. Economic Outcomes Direct medical costs Cost of drug Cost of drug administration Cost of treating adverse events Direct nonmedical costs Transporation to clinic Indirect Costs Lost work days Decreased productivity Lost earnings Intangible costs Pain Suffering Clinical Outcomes Efficacy Onset of action Percentage of patients who become pain free Recurrence of symptoms Adverse events Humanistic Outcomes Health-related quality of life Return to normal functioning Satisfaction with therapy Some category examples may be relevant to a significant other or caregiver as well as the patient. The relevance of each type of outcome is dependent chiefly on the clinical characteristics of a disease. For example, the indirect cost of lost work days may be relevant in the treatment of a disease with debilitating symptoms, such as migraine, but have less relevance in a silent, less symptomatic disease, such as hypertension or glaucoma. Chronic diseases with high prevalence and expenditure rates have been first priority for identifying which treatments offer the most value by maintaining or improving quality of care in a cost-efficient manner. Many of these first-priority areas have been addressed to date, and the outcomes movement is now expanding to assess the value of treatments for acute or less prevalent diseases that have several alternative medical treatments available. Given the recent advances in therapies for many diseases of the eye, ophthalmologic treatments should be expected to come under increasing value scrutiny. Glaucoma is an obvious choice, given the number of recently introduced alternative treatments for this chronic disease that effects a growing segment of our population. Perhaps less obvious is the need to assess the comparative value of treatments for ocular infections that are less prevalent and generally of a more acute nature. Over the past few years, however, an increasing array of new, broader spectrum, higher cost treatments (antibacterials, antifungals, and antivirals) have become available, making relative value decisions more important. The purpose of this article is to describe the basic principles of pharmacoeconomic analyses that can be used to enhance the treatment selection process for ocular infections by including a value component.