Gary N. Holland

The Tubulointerstitial Nephritis and Uveitis Syndrome

The worlds medical literature on tubulointerstitial nephritis and uveitis (TINU) syndrome was reviewed, and data on 133 patients with TINU syndrome were identified. The median age of onset was 15 years (range 9-74 years) with a 3:1 female-to-male predominance. Common laboratory abnormalities included elevated Westergren erythrocyte sedimentation rates and elevated urinary beta-2-microglobulin levels. Ocular symptoms preceded systemic symptoms in 21% of cases, and followed systemic symptoms by up to 14 months in 65% of cases. Uveitis involved only the anterior segment in 80% of cases. Uveitis was bilateral at presentation in 77% of cases. Patients were treated with systemic corticosteroids in 80% of cases and with immunosuppressive drugs in 9% of cases. Uveitis recurred or followed a chronic course in 56% of patients and persisted for several years in some cases. Ocular complications (including posterior synechiae, cataracts, and elevated intraocular pressure) were reported in 21% of cases. The visual prognosis appears to be good. Persistent renal dysfunction was reported in 11% of cases, including five patients who required renal dialysis. TINU syndrome is a distinct clinical entity that may be under-recognized and may account for some cases of unexplained chronic or recurrent uveitis. It is important for ophthalmologists, nephrologists, and primary care providers to be familiar with this disorder to ensure early diagnosis and appropriate treatment.

Ocular Disorders Associated with a new Severe Acquired Cellular Immunodeficiency Syndrome

Among the prominent features of a newly described acquired cellular immunodeficiency syndrome that affects previously healthy male homosexuals are multiple opportunistic infections and Kaposis sarcoma. Immunosuppression induced by cytomegalovirus infection may play a major role in the pathogenesis of this disorder. We have performed ophthalmic examinations on seven such patients and found ocular abnormalities in all cases. Six patients were examined during the course of their illness and one patient at autopsy only. Each patient had several cotton-wool spots in the affected eye. Other ocular findings included cytomegalovirus retinitis, severe retinal periphlebitis, and conjunctival Kaposis sarcoma (one case each).

The effect of Long-term intermittent trimethoprim/sulfamethoxazole treatment on Recurrences of toxoplasmic retinochoroiditis

PURPOSEnTo determine the effect of long-term intermittent trimethoprim/sulfamethoxazole treatment on recurrences of toxoplasmic retinochoroiditis.nnnDESIGNnProspective randomized open-labeled interventional clinical trial.nnnMETHODSnA total of 124 patients with a history of recurrent toxoplasmic retinochoroiditis were randomized to treatment with one tablet of trimethoprim (160 mg)/sulfamethoxazole (800 mg) (Bactrim F; Roche Pharmaceuticals, Rio de Janeiro, Brazil) every 3 days (61 patients) or to observation without treatment (63 patients) and were followed monthly for up to 20 consecutive months for clinical signs of disease recurrence. A recurrence was defined as a new focus of necrotizing retinochoroiditis with active inflammation either adjacent to or remote from preexisting retinochoroidal scars.nnnRESULTSnRecurrences developed in four (6.6%) treated patients and in 15 (23.8%) controls (P =.01). Treatment was discontinued prematurely in four patients because of mild drug reactions.nnnCONCLUSIONnLong-term intermittent treatment with trimethoprim/sulfamethoxazole can reduce the rate of recurrent toxoplasmic retinochoroiditis.

A follow-up study of Toxoplasma gondii infection in southern Brazil ☆

PURPOSEnTo understand better the natural history of ocular toxoplasmosis by reexamining a well-characterized population in Southern Brazil.nnnMETHODSnOphthalmological examination and serologic tests for Toxoplasma gondii infection were performed in 1997 on 383 individuals who had undergone the same evaluation in 1990.nnnRESULTSnOf 109 seronegative subjects in 1990, 21 (19.3%) became seropositive by 1997, and 2 (1.5% of previously seronegative patients; 9.5% of those known to have seroconverted) developed ocular toxoplasmosis. Seroconversion occurred more frequently in individuals under 17 years of age (16 of 46 patients, 34.8%) than in those greater than 17 years of age (5 of 63 patients, 7.9%; p = 0.002). Of 131 seropositive individuals who did not have ocular lesions in 1990, 11 (8.3%) had typical toxoplasmic lesions in 1997. Of the 13 individuals with non-specific hyperpigmented small retinal lesions in 1990, 3 (23%) presented with typical lesions in 1997.nnnCONCLUSIONSnAcquired T. gondii infection can result in late development of ocular lesions. Small, non-specific hyperpigmented retinal lesions may represent sites of T. gondii infection in seropositive individuals.

An update on current practices in the management of ocular toxoplasmosis

PURPOSEnTo update information that was published by the AMERICAN JOURNAL OF OPHTHALMOLOGY in 1991 about treatment practices for ocular toxoplasmosis by uveitis specialists.nnnDESIGNnPhysician survey.nnnMETHODSnA written questionnaire was distributed to all physician-members (n = 147) of the American Uveitis Society. The questionnaire was modeled after a similar device used to survey uveitis specialists in 1991. Information contained on 96 returned questionnaires was tabulated.nnnRESULTSnAmong 79 respondents who evaluate and manage patients with ocular toxoplasmosis, 15% treat all cases regardless of clinical findings (in contrast to 6% in 1991). The major indications for treatment among other respondents were severe inflammatory responses and proximity of retinal lesions to the fovea and optic disk. The majority of clinical factors considered in five categories (vision, lesion location, lesion size, lesion characteristics, and vitreous inflammatory reaction) were identified to be relative or absolute indications for treatment by a greater proportion of respondents in the current survey than in the 1991 survey. A total of nine drugs (or commercially available combinations) were used in 24 different regimens as treatments of choice for typical cases of recurrent toxoplasmic retinochoroiditis, with the combination of pyrimethamine, sulfadiazine, and prednisone being the most commonly used regimen (29% of respondents).nnnCONCLUSIONSnUveitis specialists appear to be more likely to treat patients with ocular toxoplasmosis in 2001 than in 1991. Although the majority of survey respondents adhere to a traditional approach to the management of toxoplasmic retinochoroiditis (a discrete course of systemic drug treatment during active disease using multiple antiparasitic drugs with or without corticosteroids), there is still no consensus regarding the choice of antiparasitic agents for treatment regimens. Survey results provide useful information for treating physicians and for clinical investigators interested in therapy.

AIDS and ophthalmology: the first quarter century.

PURPOSEnTo 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.nnnDESIGNnLiterature review and commentary.nnnMETHODSnSelected articles from the medical literature and the authors clinical and research experiences over 25 years were reviewed critically.nnnRESULTSnThe 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.nnnCONCLUSIONSnOcular 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.

Cluster of Mycobacterium Chelonae keratitis cases following laser in-situ keratomileusis ☆

PURPOSEnTo describe a cluster of Mycobacterium chelonae keratitis cases involving patients who underwent laser in-situ keratomileusis (LASIK) at a single refractive surgery center.nnnDESIGNnDescriptive case series of four patients and cohort study to identify disease associations.nnnMETHODSnExamination schedules, diagnostic tests, and therapy were based on best medical judgment. Isolates from three patients were compared by pulsed-field gel electrophoresis. Epidemiologic studies were performed to identify the source of infection.nnnRESULTSnSeven of eight eyes developed M. chelonae keratitis following bilateral simultaneous LASIK. Each patient was thought to have diffuse lamellar keratitis initially, but all seven eyes were noted to have opacities suggestive of infectious keratitis by 13 to 21 days after surgery. All eyes had undergone hyperopic LASIK over four days in April 2001 by one surgeon in a community-based refractive surgery center. A cohort study of all patients undergoing LASIK at the same center in April 2001 revealed that M. chelonae keratitis occurred only in persons undergoing correction of hyperopia (seven of 14 eyes vs. none of 217 eyes undergoing myopic LASIK, P <.001). The only difference identified between procedures was use of masks created from a soft contact lens in hyperopic LASIK. Three isolates (three patients) were indistinguishable by pulsed-field gel electrophoresis. Eyes were treated with a combination of antimicrobial agents, including topical azithromycin in three patients, with resolution of infection in all eyes over 6 to 14 weeks. The source of infection was not identified on environmental cultures.nnnCONCLUSIONnPostoperative nontuberculous mycobacterial keratitis can occur in an epidemic fashion following LASIK. Topical amikacin, azithromycin, clarithromycin, ciprofloxacin, or a combination of these agents, appears to be effective treatment for these infections.

Current Practices in the Management of Ocular Toxoplasmosis

To determine current practices in the management of ocular toxoplasmosis, 72 of 85 uveitis specialists (85%) in the American Uveitis Society completed a detailed questionnaire. Questions involved the indications for beginning treatment, choice of antiparasitic/antimicrobial agents, and experience with treatment of ocular toxoplasmosis in special situations including pregnancy, neonatal infections, and immunocompromised patients. Most of the respondents treat patients whose visual acuity had decreased to worse than 20/200, lesions located in the peripapillary, perifoveal, or maculopapillary bundle regions, and lesions associated with severe vitreous inflammation. Most would not treat patients who retained visual acuity of 20/20, lesions located in the far peripheral retina, or lesions associated with only trace to mild vitreous inflammation. Treatment of other combinations of factors remains controversial. Eight different antimicrobial drugs are used in various combinations for lesions threatening the macula or optic nerve head. Systemic corticosteroids are used by 59 of 62 respondents (95%) as part of their initial treatment regimen. The most commonly used regimens are pyrimethamine/sulfadiazine/corticosteroids (20 of 62 [32%]) and pyrimethamine/sulfadiazine/clindamycin/corticosteroids (17 of 62 [27%]). Adjunctive therapies (photocoagulation, cryotherapy, or vitrectomy) have been used by 20 of 60 respondents (33%). Most alter treatment during pregnancy, in newborn patients, and in patients with the acquired immunodeficiency syndrome.

Association between Vogt-Koyanagi-Harada Syndrome and HLA-DR1 and -DR4 in Hispanic Patients Living in Southern California

BACKGROUNDnVogt-Koyanagi-Harada (VKH) syndrome is associated with human leukocyte antigen (HLA)-B54, -DR4, -DR beta 1*0405, -DQ4, and -DR53 in Japanese patients. Disease-associated HLA specificities may differ among races. This study examined HLA associations with VKH syndrome in Hispanic patients living in southern California, a racial subgroup at increased risk for the disease.nnnMETHODSnHuman leukocyte antigen specificities were determined on 25 Hispanic patients with VKH syndrome and compared with HLA specificities of 217 healthy Hispanic control subjects. Inclusion criteria for study patients were nontraumatic panuveitis with exudative retinal detachments, with or without extraocular manifestations. Tests were performed using standard cytotoxic assays.nnnRESULTSnHLA-DR4 was present in 14 (56%) patients with VKH syndrome and in 62(29%) control subjects (relative risk = 1.96). HLA-DR1 was present in 9 (36%) patients with VKH syndrome and in 19 (9%) control subjects (relative risk = 4.11). HLA-DR1 and DR4 share a common epitope within the DR beta 1 gene. HLA-DR1 and/or DR4 were present in 21 (84%) patients with VKH syndrome and in 76 (35%) control subjects (relative risk = 2.40).nnnCONCLUSIONSnHLA-DR1 and -DR4 were found in a significantly disproportionate number of Hispanic patients with VKH syndrome living in southern California. HLA-DR4, although not HLA-DR1, has been previously associated with VKH syndrome in other groups. These associations suggest a common immunogenic predisposition to VKH among different racial groups, and suggest that a common epitope shared by DR1 and DR4 may be involved in the pathogenesis of the disease.

The progressive outer retinal necrosis syndrome

The progressive outer retinal necrosis (PORN) syndrome is a recently described clinical variant of necrotizing herpetic retinopathy in patients with the acquired immunodeficiency syndrome (AIDS). It is caused by varicellazoster virus infection of the retina. Its course and clinical features distinguish it from the acute retinal necrosis syndrome and CMV retinopathy. Early disease is characterized by multifocal deep retinal opacification. Lesions rapidly coalesce and progress to total retinal necrosis over a short period of time. Despite aggressive therapy with intravenous antivirial drugs, prognosis is poor; disease progression and/or recurrence is common, and the majority of patients develop no light perception vision. Total retinal detachments are common. Prophylaxis against retinal detachment using laser retinopexy has not been useful in most cases. PORN syndrome is an uncommon, but devastating complication of AIDS.