Ischemic maculopathy in patients with acquired immunodeficiency syndrome.

PURPOSE: To describe the characteristics of ischemic maculopathy in patients with human immunodeficiency virus (HIV) infection, as a means of understanding this uncommon disorder more fully. METHODS: This is a multicenter, retrospective review of clinical data available for five HIV-infected patients who were given the diagnosis of ischemic maculopathy. RESULTS: All cases had been diagnosed on the basis of fluorescein angiograms obtained after patients complained of vision loss. Four of the five patients had bilateral macular disease. Visual acuity at presentation in the nine affected eyes ranged from 20/20 to count fingers. Vision loss was gradual in both eyes of one patient and was abrupt in onset in seven eyes. Each of the seven eyes with abrupt vision loss had opacification of the superficial retina and/or intraretinal hemorrhages near the fovea. Fluorescein angiography revealed enlargement of the foveal avascular zone and mild staining of the juxtafoveal vessels in affected eyes. Six eyes had active or clinically inactive cytomegalovirus retinitis at presentation, and a seventh eye developed cytomegalovirus retinitis 2 weeks later. All patients were receiving anticytomegalovirus drugs when they developed visual symptoms. Visual acuity remained stable in five eyes, became worse in two eyes, and improved in two eyes; final visual acuity ranged from 20/25 to count fingers. CONCLUSIONS: Ischemic maculopathy may cause profound and permanent vision loss in HIV-infected individuals. Fluorescein angiography should be considered in all HIV-infected patients with unexplained loss of vision. The pathogenesis of ischemic maculopathy remains unknown.

An association between Vogt-Koyanagi-Harada disease and Guillain-Barré syndrome.

PURPOSE: To describe an association between Vogt-Koyanagi-Harada disease and Guillain-Barré syndrome. METHODS: Case series, describing three patients. RESULTS: In two patients, the disorders had their onsets within 2 weeks of each other; in the third patient, Vogt-Koyanagi-Harada disease occurred after 3 months, as Guillain-Barré syndrome resolved. All three patients had bilateral panuveitis typical of Vogt-Koyanagi-Harada disease. Each also developed well-accepted manifestations of Guillain-Barré syndrome, including paresis of the lower extremities (all patients), paresis of the upper extremities (two patients), paresis of cranial nerves (two patients), areflexia (all patients), and abnormal electromyography findings (two patients). CONCLUSIONS: Vogt-Koyanagi-Harada disease may follow or occur simultaneously with Guillain-Barré syndrome. The fact that these two autoimmune disorders occur together in some patients suggest that they may share common disease mechanisms.

Use of the ganciclovir implant for the treatment of cytomegalovirus retinitis in the era of potent antiretroviral therapy: recommendations of the International AIDS Society-USA panel.

PURPOSE: To describe the risks, benefits, and recommended use of the ganciclovir implant for the treatment of human immunodeficiency virus-related cytomegalovirus (CMV) retinitis in the era of potent antiretroviral therapy. METHODS: A panel of physicians with expertise in the use of the ganciclovir implant and in the management of CMV retinitis was convened by the International AIDS Society-USA. The panel reviewed and discussed available data, and developed recommendations for the use of the ganciclovir implant, the surgical technique, and related management issues. Recommendations were rated according to the strength and quality of the supporting evidence. RESULTS: The effect of potent antiretroviral therapy on the immunologic status of patients with human immunodeficiency virus disease has changed the manifestation and course of CMV retinitis in many patients. The clinical management of CMV retinitis and the role of the ganciclovir implant are thus changing. Factors in the decision to choose the ganciclovir implant include the patient's potential for immunologic improvement, location and severity of CMV retinitis, and the risks and costs associated with implantation and concomitant oral ganciclovir therapy. CONCLUSIONS: The ganciclovir implant is safe and effective for the treatment of CMV retinitis. The indications for its use should be modified to account for increased patient survival and the potential for CMV retinitis to be controlled by effective antiretroviral therapy. Optimal use of the ganciclovir implant and discontinuation of therapy in selected patients with improvement in immunity may result in better long-term visual outcomes.

Surfing-related ocular injuries.

PURPOSE: This report evaluates the clinical characteristics of surfing-related ocular trauma to learn the nature of such injuries and propose possible preventive measures. METHODS: The authors reviewed 11 cases of surfing-related eye injuries caused by direct trauma from the surfboard, studying their mechanism of injury, the associated ocular complications, and the anatomic and visual outcomes of surgical repair. RESULTS: Surfing-related ocular injuries occurred exclusively in young males (mean age, 24.8 years; range, 14-37 years). The mechanism of injury most frequently responsible was impact with the sharp nose of the surfboard following a fall. Serious posterior segment complications were observed in all 11 patients, with nine patients suffering ruptured globes. Despite immediate medical attention, five patients did not recover ambulatory levels of visual acuity (>5/200). CONCLUSIONS: Surfing-related ocular trauma presenting to the retinal specialist typically leaves the patient with a permanent visual disability. Important factors contributing to these high-velocity injuries include the sharply pointed nose of the surfboard and the leash keeping the surfer in close proximity to the board following a fall. A simple modification in surfboard design such as blunting the sharp nose of the surfboard, or appropriate protective guards fitted over the surfboard nose, should lessen the severity of such injuries.

Bilateral endogenous Fusarium endophthalmitis associated with acquired immunodeficiency syndrome.

A 51-year-old man with acquired immunodeficiency syndrome and cytomegalovirus retinitis had bilateral endogenous fungal endophthalmitis. Cultures yielded Fusarium species. Histopathologic examination showed a severe necrotizing acute and granulomatous reaction, with numerous fungal elements in the retina and uveal tract. Fungal elements were seen in the lens, sclera, and emissarial vessels. Angiopathic infiltration by fungus and widespread thrombosis produced retinal and choroidal infarction. In some areas, fungal infection coexisted with cytomegalovirus retinitis. The bilateral distribution suggests hematogenous seeding of the eyes. The eye findings were the first clinically apparent manifestations of fungal disease in this patient.

Local therapy for cytomegalovirus retinopathy.

PURPOSE: We sought to understand better the efficacy and risks of local therapies (direct placement of drug into the eye) for the treatment of cytomegalovirus retinopathy. This understanding can be used to design rational treatment regimens, to formulate indications for use of local therapy, and to establish criteria for assessment of future results in this area. METHODS: We collected information about local therapies through a review of published literature. RESULTS: Intraocular injection of ganciclovir and foscarnet and implantation of intraocular devices that slowly release ganciclovir are able to decrease the activity of cytomegalovirus retinopathy lesions and prevent their enlargement for variable periods of time. The time to disease progression (lesion enlargement) may be longer with intraocular devices than with current treatments using intravenously administered antiviral drugs. Local therapies have many advantages (for example, convenience, reduced cost, and lack of systemic toxicity), but there are potential disadvantages, including endophthalmitis, increased rates of retinal detachment, and development of nonocular cytomegalovirus disease and cytomegalovirus retinopathy in fellow, uninvolved eyes. CONCLUSIONS: Local therapies are effective for the treatment of cytomegalovirus retinopathy, but their relative risks and benefits, when compared with those of intravenous drug therapy, have yet to be fully evaluated. We anticipate that local therapy will be an important treatment modality for selected patients with cytomegalovirus retinopathy. Indications include the use of local therapy as an alternative therapy for patients who are unable to receive systemic therapy (intolerance to intravenous or oral medication, or lack of intravenous access) and as supplementation in patients whose retinal disease is incompletely controlled by maximum tolerated systemic medications. The use of local therapy as sole initial treatment in lieu of systemic therapy remains controversial. Its most useful role may be in conjunction with oral forms of antiviral drugs now in development.

The progressive outer retinal necrosis syndrome. A variant of necrotizing herpetic retinopathy in patients with AIDS.

BACKGROUND: The progressive outer retinal necrosis syndrome is a recently recognized variant of necrotizing herpetic retinopathy. This report characterizes more fully its clinical features and course. METHODS: Using standardized clinical criteria, patients with progressive outer retinal necrosis syndrome from four institutions were identified. Patient records were reviewed retrospectively for the following data: medical and demographic characteristics, presenting symptoms, physical findings, course, responses to treatment, and outcomes. RESULTS: Thirty-eight patients (65 involved eyes) were studied. All had acquired immune deficiency syndrome. A known history of cutaneous zoster was documented in 22 (67%) of 33 patients. Median CD4 lymphocyte count was 21/mm3 (range, 0-130/mm3). Median follow-up was 12 weeks. The most common presenting symptom was unilateral decreased vision (35 of 65 eyes, 54%); median visual acuity at presentation was 20/30 (range, 20/20 to no light perception [NLP]). Anterior chamber and vitreous inflammatory reactions were absent or minimal in all patients. Typical retinal lesions were multifocal, deep opacities scattered throughout the periphery, although macular lesions also were present in 21 eyes (32%) at diagnosis. Lesions progressed rapidly to confluence. Initial intravenous antiviral therapy appeared to reduce disease activity in 17 (53%) of 32 eyes, but treatment did not alter final visual outcome. Visual acuity was NLP in 42 (67%) of 63 eyes within 4 weeks after diagnosis. Retinal detachment occurred in 43 (70%) of 61 eyes, including 13 (93%) of 14 eyes that received prophylactic laser retinopexy. CONCLUSION: The progressive outer retinal necrosis syndrome is characterized by features that distinguish it from cytomegalovirus retinopathy, acute retinal necrosis syndrome, and other necrotizing herpetic retinopathies. Visual prognosis is poor with current therapies.

Recurrence of presumed varicella-zoster virus retinopathy in patients with acquired immunodeficiency syndrome.

Five patients with acquired immunodeficiency syndrome (AIDS) and presumed varicella-zoster virus retinopathy had recurrence of retinopathy after stabilization with initial intravenous antiviral therapy. Recurrences were recognized as increased retinal opacification at the borders of preexisting lesions or as new lesions. In four of the five patients, recurrences were temporally associated with a reduction in the amount of antiviral medication being received. Changes included switch from intravenous to oral acyclovir (two patients), taper of oral acyclovir (one patient), and discontinuation of medications (one patient). In four patients disease was initially unilateral; in three of these four, disease subsequently developed in the previously unaffected fellow eye at the time of recurrence. The median time from stabilization of disease to recurrence was 51 days (range, 14 to 90 days). In contrast to the management of varicella-zoster virus retinopathy in immunocompetent patients and varicella-zoster virus lesions of the skin, varicella-zoster virus retinopathy in patients with AIDS appears to require chronic suppressive antiviral therapy to prevent recurrences. In this respect it is similar to other opportunistic retinal infections in patients with AIDS. The best drugs and optimal treatment regimens for maintenance antiviral therapy remain unknown.

Immune response to Staphylococcus epidermidis-induced endophthalmitis in a rabbit model.

Although Staphylococcus epidermidis is the most common cause of postoperative pseudophakic endophthalmitis, little is known about the immune response to S. epidermidis-induced endophthalmitis. Using a rabbit model, the immune response to an intravitreal injection of 7000 S. epidermidis (group 1) or 30,000 S. epidermidis (group 2) organisms was investigated. Clinical evaluations showed that rabbits in group 2 had a more severe inflammatory reaction in the conjunctiva, cornea, iris, and vitreous than those in group 1. The inflammatory reaction in group 1 largely resolved by day 30; group 2 continued to show a severe inflammatory response. Histopathologic findings correlated with clinical findings, with rabbits in group 2 showing a more severe inflammatory reaction in both the anterior and posterior segments of the globe. Positive vitreous cultures for S. epidermidis were present in rabbits in group 1 on days 3, 7, 10, 14, and 21 but not thereafter. However, group 2 had higher vitreous colony counts at days 3, 7, and 14 and negative vitreous cultures thereafter. Neither group showed delayed hypersensitivity to S. epidermidis antigens (evaluated by skin tests). Serum immunoglobulin (Ig) G antibody levels to phenol-inactivated S. epidermidis and glycerol teichoic acid (GTA) increased progressively, reached a peak at days 10-14, and then declined in both groups. Serum IgA antibody levels to these antigens were not detected. Group 2 had a more prolonged IgG antibody response in vitreous and aqueous than group 1. Tear fluid showed the weakest IgG and IgA antibody response to S. epidermidis and GTA. S. epidermidis-induced endophthalmitis was associated with a humoral but not a delayed hypersensitivity response to this organism.

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.

Immune response to Staphylococcus aureus endophthalmitis in a rabbit model.

Staphylococcus aureus is an important cause of severe bacterial endophthalmitis. Both immunoglobulin (Ig) G and A antibody titers to ribitol teichoic acid (RTA), the major antigenic determinant of the S. aureus cell wall, were measured by an enzyme-linked immunosorbent assay in serum, tears, aqueous, and vitreous on days 3, 7, 10, 14, 21, and 30 after intravitreal injection of viable S. aureus in rabbits. Clinical examination showed vitreous opacification in all rabbits from days 7-30. Histopathologic examination showed acute inflammation on day 3 and chronic inflammation on days 7-30 in the conjunctiva, cornea, iris, ciliary body, and trabecular meshwork. The vitreous cavity contained neutrophils and necrotic cells on all days. Retinal necrosis was present on days 14-30. Lymphoid follicles with plasma cells were identified in the conjunctiva, ciliary body, and choroid. The vitreous of experimental eyes showed increasing numbers of bacteria from days 3-14, followed by a decrease in numbers on day 21 and absence of viable bacteria on day 30. Increases in IgG antibody levels to RTA were first detected in serum where they were higher than in tears, aqueous, and vitreous until day 14. Vitreous IgG antibody levels to RTA in experimental eyes exceeded all other samples on day 14 and progressively increased thereafter; the other samples declined. The IgA antibody levels were increased in tears on day 14 and in the vitreous of experimental eyes on days 14, 21, and 30. Vitreous IgG antibody levels to RTA were substantially higher than vitreous IgA antibody levels. An inverse correlation was found between vitreous IgG antibody levels and positive vitreous cultures, suggesting that the humoral immune response may be important in the spontaneous sterilization of the vitreous in this model.

Collagen shield delivery of amphotericin B.

By using a high-pressure liquid chromatography assay, we investigated the ability of collagen shield therapeutic contact lenses to release amphotericin B and deliver it to the anterior segment of rabbit eyes. In vitro studies showed that presoaked collagen shields released most of the amphotericin B within the first hour of elution. We compared the corneal and aqueous humor amphotericin B levels produced by collagen shields soaked in amphotericin B and frequent-drop therapy at four time points over a six-hour period. The collagen shields soaked in amphotericin B produced corneal levels that were higher than those produced by frequent-drop therapy at one hour, equivalent to drop therapy at two and three hours, and lower than drop therapy at six hours. There were no differences in amphotericin B levels in aqueous humor at any time point between rabbits treated with collagen shield delivery and rabbits treated with frequent-drop delivery. The results of this study suggest that amphotericin B delivery to the cornea by collagen shields is comparable to frequent-drop delivery but has the potential benefit of added convenience and compliance.

Hemorheologic abnormalities in patients with human immunodeficiency virus infection and ophthalmic microvasculopathy.

The severity of conjunctival microvascular changes and the presence of cotton-wool spots were compared to factors that may affect blood flow (hematocrit level, red cell aggregation, fibrinogen level, plasma viscosity, circulating immune complexes, and quantitative immunoglobulin levels) in 22 human immunodeficiency virus-infected individuals. The severity of conjunctival disease was associated with increased zeta sedimentation ratios (a measure of red cell aggregation) and fibrinogen levels. The presence of cotton-wool spots was also associated with higher fibrinogen levels. Plasma viscosity and quantitative IgG levels were above normal levels in most patients, although a relationship to disease severity was not established. Altered blood flow may contribute to vascular damage and ocular ischemic lesions in patients with human immunodeficiency virus infection.

Herpes simplex keratitis in patients with acquired immune deficiency syndrome.

Acquired immune deficiency syndrome (AIDS) is associated with a wide spectrum of systemic and ocular infectious diseases. Little information is known about herpes simplex virus type 1 (HSV-1) keratoconjunctivitis in association with AIDS. The authors present six cases of recurrent HSV keratitis occurring in AIDS patients. Features of the herpetic keratitis in these patients included unilateral dendritic or geographic epithelial keratopathy; predilection for peripheral versus central corneal involvement; one to three recurrences per patient over a mean observation period of 17 months, with a median dendrite-free interval of 7 months; and a moderately prolonged clinical course with a median healing time of 3 weeks using topical antiviral therapy. Only one of six cases had stromal infiltrative involvement. These cases raise the question of whether the immunologic abnormalities associated with AIDS may affect the clinical characteristics and course of HSV keratitis.

Ocular toxoplasmosis in patients with the acquired immunodeficiency syndrome.

In seven of eight cases of presumed ocular toxoplasmosis in patients with AIDS, the diagnosis was supported by a reduction or resolution of intraocular inflammation and healing of necrotic retinal lesions after initiation of antiparasitic drug therapy including one or more of the following medications: pyrimethamine, sulfadiazine, clindamycin, tetracycline, or spiramycin. In two cases the diagnosis was confirmed histologically. The cases differed clinically and histopathologically from those in immunocompetent patients. There was no evidence that disease originated in preexisting retinochoroidal scars. Lesions frequently were bilateral and multifocal. Vitreous inflammatory reaction was a common clinical finding, but histopathologic examination demonstrated scant retinal inflammation in areas of necrosis. Ocular toxoplasmosis in these patients with AIDS probably resulted from newly acquired infection or dissemination of organisms from nonocular sites of disease. Infections became clinically inactive with drug therapy in all treated patients, but reactivation and progression of disease occurred when therapy was stopped in two of three patients. Severe retinal necrosis led to retinal tears or detachment in three cases. Ocular lesions were the first manifestation of Toxoplasma gondii infection in four of five patients with evidence of multisystem infection.