Purpose To describe changes in the acquired immunodeficiency syndrome (AIDS) epidemic that are important to ophthalmologists, to provide an overview of issues relevant to current evaluation and ...treatment of human immunodeficiency virus (HIV)-related eye disease, and to identify problems related to the eye and vision that require continued study. Design Literature review and commentary. Methods Selected articles from the medical literature and the author’s clinical and research experiences over 25 years were reviewed critically. Results The AIDS epidemic has had a profound impact on ophthalmology since the ophthalmic manifestations of AIDS were first described in 1982. The introduction of highly active antiretroviral therapy (HAART) has markedly reduced the incidence of cytomegalovirus (CMV) retinitis, but has not eliminated new cases altogether. Treatment strategies for CMV retinitis have evolved over the past decade. Current issues of importance include choice of initial anti-CMV drugs; time at which anti-CMV drug treatment is discontinued in patients who achieve immune recovery; strategies for monitoring patients at risk for disease reactivation; and management of complications (retinal detachment, immune recovery uveitis). Attention also is being directed to the problem of visual disturbances (reduced contrast sensitivity, altered color vision, visual field abnormalities) that can occur in HIV-infected individuals without infectious retinopathies. Conclusions Ocular disorders associated with HIV disease remain important problems in the United States, despite HAART, and increasingly are important worldwide. The approach to management of CMV retinitis has evolved from short-term treatment of a preterminal infection to the long-term management of what has become a chronic disease. Many challenges remain to be addressed.
To update clinical information about ocular toxoplasmosis. Part I reviews information about prevalence of disease, sources of infection, relation of ocular disease to time of
Toxoplasma gondii ...infection (congenital vs. postnatally acquired), and course of disease.
Literature review.
Selected articles from the medical literature, information from recent scientific meetings, and the author's personal experiences were reviewed critically in preparation for the LX Edward Jackson Memorial Lecture.
The prevalence of
T. gondii infection varies geographically and increases with age; in the United States, the overall proportion is 22.5%. The proportion of infected individuals in the United States who have had episodes of ocular toxoplasmosis is unknown, but may be approximately 2%. Prevalence of ocular involvement is substantially greater in other parts of the world, including southern Brazil. In addition to undercooked meat and unwashed vegetables, drinking water contaminated with oocysts may be an important source of infection in some settings. In contrast to traditional teaching, evidence suggests that most individuals with ocular toxoplasmosis were infected postnatally. Ocular lesions may first develop many years after
T. gondii infection. The risk of recurrent ocular disease appears to be greater during the first year after an episode of toxoplasmic retinochoroiditis than during subsequent years.
Reassessment of older publications in the light of recent observations provides a richer understanding of ocular toxoplasmosis, although knowledge about the disease remains incomplete. A better understanding of the clinical characteristics and course of ocular toxoplasmosis will have important implications for developing more effective prevention and treatment strategies.
The protozoan parasite Toxoplasma gondii is one of the most widely distributed and successful parasites. Toxoplasma gondii alters rodent behavior such that infected rodents reverse their fear of cat ...odor, and indeed are attracted rather than repelled by feline urine. The location of the parasite encysted in the brain may influence this behavior. However, most studies are based on the highly susceptible rodent, the mouse.
Latent toxoplasmosis was induced in rats (10 rats per T. gondii strains) of the same age, strain, and sex, after oral inoculation with oocysts (natural route and natural stage of infection) of 11 T. gondii strains of seven genotypes. Rats were euthanized at two months post inoculation (p.i.) to investigate whether the parasite genotype affects the distribution, location, tissue cyst size, or lesions. Tissue cysts were enumerated in different regions of the brains, both in histological sections as well in saline homogenates. Tissue cysts were found in all regions of the brain. The tissue cyst density in different brain regions varied extensively between rats with many regions highly infected in some animals. Overall, the colliculus was most highly infected although there was a large amount of variability. The cerebral cortex, thalamus, and cerebellum had higher tissue cyst densities and two strains exhibited tropism for the colliculus and olfactory bulb. Histologically, lesions were confined to the brain and eyes. Tissue cyst rupture was frequent with no clear evidence for reactivation of tachyzoites. Ocular lesions were found in 23 (25%) of 92 rat eyes at two months p.i. The predominant lesion was focal inflammation in the retina. Tissue cysts were seen in the sclera of one and in the optic nerve of two rats. The choroid was not affected. Only tissue cysts, not active tachyzoite infections, were detected. Tissue cysts were seen in histological sections of tongue of 20 rats but not in myocardium and leg muscle.
This study reevaluated in depth the rat model of toxoplasmosis visualizing cyst rupture and clarified many aspects of the biology of the parasite useful for future investigations.
To update clinical information about ocular toxoplasmosis. Part II reviews the spectrum of disease manifestations and factors that influence severity of disease. Implications for disease management ...are discussed.
Literature review.
Selected articles from the medical literature, information from several recent scientific meetings, and the author's personal experiences were reviewed critically in preparation for the LX Edward Jackson Memorial Lecture.
The appearance of toxoplasmic retinochoroiditis lesions varies with duration of active retinal infection and intensity of inflammation. Severe ocular disease occurs in immunocompromised hosts. Older patients who are recently infected with
Toxoplasma gondii may have a higher prevalence of ocular involvement and more severe ocular disease because of altered host defenses. Most disease-producing isolates of
T. gondii belong to one of three clonal lineages (types I, II, III); type I has been associated with severe disease in both animals and human beings. Many observational studies suggest a benefit of short-term antimicrobial therapy for toxoplasmic retinochoroiditis in immunocompetent patients, although the efficacy of these treatments has not been proven in randomized clinical trials. Intermittent trimethoprim/sulfamethoxazole treatment was associated with fewer recurrences than placebo during a 20-month randomized clinical trial.
Variations in disease characteristics may be related to host, parasite, or environmental factors. The genotype of the infecting parasite appears to be an important determinant of disease severity in immunocompetent patients. Secondary prophylaxis may reduce the rate of recurrences in high-risk patients. A better clinical understanding of ocular toxoplasmosis can lead to more effective prevention and treatment strategies.
To investigate a possible effect of intraocular inflammation on corneal endothelium by describing corneal endothelial cell density (ECD) and morphologic variables in eyes with anterior uveitis, and ...to investigate factors that may influence these findings.
Cross-sectional, observational study. Observers were not masked.
Volunteers with histories of unilateral or bilateral anterior segment inflammation (anterior, intermediate, or panuveitis); included were 52 patients (84 eyes with uveitis).
Endothelial cell density and morphologic variables of both eyes of all study participants were determined by specular microscopy; central corneal thickness was determined by ultrasound pachymetry.
Central corneal ECD, coefficient of variability, percentage hexagonality, and central corneal thickness.
Central ECD was lower among eyes that had undergone cataract or glaucoma surgery or both (n = 28; P = 0.0004). After exclusion of eyes with surgery, variables for eyes with uveitis (n = 56) were compared with 2 historical populations of normal, age-matched controls and with contralateral eyes in individuals with unilateral uveitis. Central ECD was lower in eyes with uveitis than in control eyes for all age groups (P ≤ 0.01 for four of six 10-year age intervals compared with the primary control group). Among patients with unilateral uveitis who had not undergone surgery in either eye (n = 12), central ECD was lower in eyes with uveitis (2324 cells/mm(2) range, 1543-3289 cells/mm(2)) than in contralateral eyes (2812.5 cells/mm(2) range, 1887-3546 cells/mm(2); P = 0.0005), and percentage hexagonality was lower in eyes with uveitis (54% range, 33%-66%) than in contralateral eyes (58.5% range, 52%-82%; P = 0.004). There was no significant difference in central corneal thickness between eyes with and without uveitis (P = 0.27). No eyes had clinically apparent central corneal edema. Relationships remained unchanged after exclusion of eyes with herpetic anterior uveitis. Host and disease-related characteristics were evaluated as risk factors for variations in outcome measures. Central ECD was correlated to the duration of active uveitis (r = -0.41; P < 0.0001), maximum intraocular pressure during the course of disease (r = -0.40; P = 0.0002), and maximum laser flare photometry value (r = -0.26; P = 0.020).
Observed relationships suggest that anterior segment inflammation adversely affects the corneal endothelium. Longitudinal studies are warranted to determine whether long-standing anterior uveitis increases risk of endothelial dysfunction, especially in the setting of intraocular surgery.
Objective
Systemic immunosuppressive treatment of pediatric chronic anterior uveitis (CAU), both juvenile idiopathic arthritis–associated and idiopathic anterior uveitis, varies, making it difficult ...to identify best treatments. The Childhood Arthritis and Rheumatology Research Alliance (CARRA) developed consensus treatment plans (CTPs) for CAU for the purpose of reducing practice variability and allowing future comparison of treatments using comparative effectiveness analysis techniques.
Methods
A core group of pediatric rheumatologists, ophthalmologists with uveitis expertise, and a lay advisor comprised the CARRA uveitis workgroup that performed a literature review on pharmacologic treatments, held teleconferences, and developed a case‐based survey administered to the CARRA membership to delineate treatment practices. We held 3 face‐to‐face consensus meetings using nominal group technique to develop CTPs.
Results
The survey identified areas of treatment practice variability. We developed 2 CTPs for the treatment of CAU, case definitions, and monitoring parameters. The first CTP is directed at children who are naive to steroid‐sparing medication, and the second at children initiating biologic therapy, with options for methotrexate, adalimumab, and infliximab. We defined a core data set and outcome measures, with data collection at 3 and 6 months after therapy initiation. The CARRA membership voted to accept the CTPs with a >95% approval (n = 233).
Conclusion
Using consensus methodology, 2 standardized CTPs were developed for systemic immunosuppressive treatment of CAU. These CTPs are not meant as treatment guidelines, but are designed for further pragmatic research within the CARRA research network. Use of these CTPs in a prospective comparison effectiveness study should improve outcomes by identifying best practice options.
Objective
To develop recommendations for the screening, monitoring, and treatment of uveitis in children with juvenile idiopathic arthritis (JIA).
Methods
Pediatric rheumatologists, ophthalmologists ...with expertise in uveitis, patient representatives, and methodologists generated key clinical questions to be addressed by this guideline. This was followed by a systematic literature review and rating of the available evidence according to the GRADE (Grading of Recommendations Assessment, Development and Evaluation) methodology. A group consensus process was used to compose the final recommendations and grade their strength as conditional or strong.
Results
Due to a lack of literature with good quality of evidence, recommendations were formulated on the basis of available evidence and a consensus expert opinion. Regular ophthalmic screening of children with JIA is recommended because of the risk of uveitis, and the frequency of screening should be based on individual risk factors. Regular ophthalmic monitoring of children with uveitis is recommended, and intervals should be based on ocular examination findings and treatment regimen. Ophthalmic monitoring recommendations were strong primarily because of concerns of vision‐threatening complications of uveitis with infrequent monitoring. Topical glucocorticoids should be used as initial treatment to achieve control of inflammation. Methotrexate and the monoclonal antibody tumor necrosis factor inhibitors adalimumab and infliximab are recommended when systemic treatment is needed for the management of uveitis. The timely addition of nonbiologic and biologic drugs is recommended to maintain uveitis control in children who are at continued risk of vision loss.
Conclusion
This guideline provides direction for clinicians and patients/parents making decisions on the screening, monitoring, and management of children with JIA and uveitis, using GRADE methodology and informed by a consensus process with input from rheumatology and ophthalmology experts, current literature, and patient/parent preferences and values.
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