Coccidioidomycosis iridocyclitis.

BACKGROUND: Coccidioidomycosis has reached epidemic proportions in the southwest region of the United States. Despite the greater numbers of cases, isolated anterior segment ocular coccidioidomycosis in the absence of systemic infection continues to be rare, although its incidence may be increasing. METHODS: Two patients without clinical evidence of systemic disease and one patient with previously treated pulmonary coccidioidomycosis had granulomatous iridocyclitis and iris nodules that were unresponsive to corticosteroid therapy. All three patients underwent iris biopsy, anterior chamber tap, and washout for histopathologic diagnosis of anterior segment disease, and all subsequently received systemic antifungal therapy. Two patients also received multiple intraocular injections of amphotericin B. RESULTS: Papanicolaou and hematoxylin-eosin-stained preparations of anterior chamber tap and biopsies of the iris in each of these patients showed fibrinopurulent or granulomatous inflammatory exudate with intact and disrupted Coccidioides spherules. Despite aggressive systemic and intraocular therapy, one patient required enucleation for a blind, painful eye. The other two patients continue to have limited visual acuity but with at least partial resolution of the intraocular lesions. CONCLUSIONS: Ocular coccidioidomycosis without clinical evidence of systemic involvement is rare. Isolated anterior segment disease is also uncommon; however, because of the current epidemic in the southwest region of the United States, ocular coccidioidomycosis should be considered in any patient who traveled through or lived in endemic areas and who has a granulomatous iridocyclitis associated with iris mass that is unresponsive to corticosteroid therapy.

Surgical management of retinal detachment associated with the acute retinal necrosis syndrome.

We operated on nine eyes in eight patients with retinal detachment associated with acute retinal necrosis (ARN) syndrome. The patients were treated with scleral buckling, vitreoretinal surgery, or a combination of these treatments. Vitrectomised eyes underwent combinations of lensectomy, membrane dissection, scleral buckling, air-fluid exchange, endolaser photocoagulation, cryotherapy, and retinal tamponade with C3F8 gas or SF6 gas. Macular attachment was achieved in eight (89%) eyes. Vision improved in seven (78%) eyes, of which five (56%) achieved 20/200 or better vision. Three eyes that had received laser treatment posterior to areas of retinitis suffered retinal detachment despite this prophylactic treatment. Poor visual outcome resulted from viral infection of the optic nerve or macular involvement, macular hole formation, macular pucker, or hypotony.

Scleral buckling for rhegmatogenous retinal detachment associated with severe myopia.

From Jan. 1, 1980, to Dec. 31, 1989, we performed scleral buckling surgery on 48 eyes of 46 patients for rhegmatogenous retinal detachments associated with severe myopia (greater than 5.00 diopters). Forty eyes of 38 patients were observed for at least six months, and the mean follow-up period was 46 months. Intraoperative complications occurred in four of 48 eyes (8%) and included retinal incarceration (two eyes), choroidal hemorrhage (one eye), and choroidal detachment (one eye). Three of the 40 eyes (7.5%) followed up for more than six months developed a recurrent retinal detachment and underwent a revision of the scleral buckle. At the last follow-up examination, the retinas of all 40 eyes were totally reattached. Final visual acuity of 20/40 or better was attained in 26 of 40 eyes (65%). Because of the low rate of intraoperative complications and the high rate of success, scleral buckling is recommended for most patients with rhegmatogenous retinal detachments associated with severe myopia.

Rhegmatogenous retinal detachments in patients with AIDS and necrotizing retinal infections.

Rhegmatogenous retinal detachments can occur in patients with acquired immune deficiency syndrome (AIDS) and necrotizing retinal infections. Of 68 patients with AIDS and necrotizing retinal infections seen between 1983 and 1987, rhegmatogenous retinal detachments developed in 16 patients (27 eyes). In this group, cytomegalovirus retinopathy was present in 75% (12 of 16) of patients, 18.8% (3 of 16) had probable herpes simplex virus retinopathy, and 6.2% (1 of 16) had toxoplasmic retinochoroiditis. Retinal detachment was bilateral in 68.8% (11 of 16) of patients. The retina was reattached successfully in 91% (10 of 11) of operated eyes. Proliferative vitreoretinopathy was present preoperatively in 95% of these eyes. Seven of 11 operated eyes had initial improvement in visual acuity. However, 5 of 11 continued to lose vision despite successful reattachment. Techniques included pneumatic reattachment, scleral buckle, vitrectomy, and silicone oil injection. Complicated retinal detachments in AIDS patients with rhegmatogenous retinal detachments and necrotizing retinal infections are common and can be repaired, but the prognosis is guarded in many patients.

Isolation and characterization of bovine choroidal microvessel endothelium and pericytes in culture.

The invasion of Bruch's membrane and subsequently the subpigment epithelial and subretinal spaces by proliferating choroidal capillaries are prominent features of age-related macular degeneration. To facilitate study of this process, pure cell lines of bovine choroidal microvessel endothelium and pericytes were isolated and propagated in cell culture media. Their biological and biochemical properties are described. Choroidal microvascular endothelial cells displayed the characteristic cobblestone morphology, required fibronectin or gelatin for attachment to plastic culture dishes, displayed contact inhibition of growth and spontaneously formed tubules in culture. These cells contained antigens for Factor VIII and were able to phagocytize acetylated-low density lipoprotein. Choroidal microvascular pericytes were nonrectangular in shape and did not require substrate attachment factors. They were unable to form tubules in culture, were Factor VIII antigen negative, were unable to phagocytize acetylated-low density lipoprotein and did not display contact inhibition of growth. Choroidal microvascular pericytes contained antigens for muscle and nonmuscle actin.

Inflammatory mediators in the vitreous humor of AIDS patients with retinitis.

We measured levels of protein, of complement-derived anaphylatoxins (C3a, C4a, and C5a), and of the lymphokines interleukin-2 and gamma interferon, in vitreous humor from 10 AIDS patients with vitritis and retinitis (group 1). We compared these measurements with levels in vitreous from 7 patients with vitritis but without AIDS (group 2), 10 patients with vitreous hemorrhages (group 3), and 20 patients with retinal detachments or epiretinal membranes without clinical evidence of vitreal inflammation (group 4). Vitreous humor from 10 AIDS patients had measurable levels of interleukin-2 in three of nine samples, gamma interferon in six of nine samples, C3a and C4a in all ten samples, and C5a in only one of ten samples. Vitreous humor from group 1 did not differ significantly from vitreous from group 2. On the other hand, vitreous from group 1 had significantly higher levels of gamma interferon, C3a, and C4a, and higher ratios of these anaphylatoxins to protein, in comparison to vitreous in groups 3 and 4. The results of this study suggest that vitreous humor from AIDS patients with retinitis contains activated complement and may contain interleukin-2 and gamma interferon. Viral retinitis is associated with the presence of lymphokines in vitreous humor. Additionally, anaphylatoxin and gamma interferon levels, but not interleukin-2 levels, correlate with vitreal inflammation. This is the first study to measure interleukin-2, gamma interferon, and C5a levels in human vitreous humor.

Localization of gamma glutamyl transpeptidase in bovine retina.

Gamma-glutamyl transpeptidase (GGTP) is a membrane bound enzyme which has an important role in regulation of glutathione and glutamate in the retina. We have used histochemical and colorimetric enzyme assays to localize GGTP in the bovine retina and choroid. Our results demonstrate that (i) GGTP is present in retinal microvessels but not choroidal microvessels. (ii) Retinal microvascular endothelium loses the ability to express GGTP in cultured cells. (iii) GGTP is present in Muller cells. (iv) Isolated and purified rod outer segments contain high levels of GGTP. (v) Retinal pigment epithelial cells (RPE) in vivo and in culture contain GGTP. The findings of this study lend support to the concept that GGTP may be a biochemical marker for cellular systems which are part of specialized diffusion barriers.

Bovine retinal pigment epithelium promotes proliferation of choroidal endothelium in vitro.

The invasion of Bruch's membrane and subsequently the subpigment epithelium and subretinal spaces by proliferating choroidal capillaries is a prominent feature of age-related macular degeneration. The ability to isolate and propagate pure cultures of bovine choroidal microvascular endothelium, choroidal pericytes, turbinate fibroblasts, and bovine retinal pigment epithelium allowed us to identify a growth-promoting activity produced by the retinal pigment epithelium that stimulated the proliferation of these cells in vitro. This mitogenic activity is present in both retinal pigment epithelium-conditioned medium and retinal pigment epithelium extract and enhances the mitogenic activity of retinal-derived extract. The activity is resistant to extremes of temperature and pH but partially sensitive to trypsin inactivation.

The successful removal of a subretinal cysticercus by pars plana vitrectomy.

A 39-year-old woman from Belize presented with recent vision loss in her left eye due to a subretinal cysticercus located near the macula. We are reporting the use of standard vitrectomy instrumentation and techniques to successfully remove the subretinal cysticercus by a transretinal approach. Pars plana vitrectomy with transretinal removal of the cysticercus is a useful alternative to the traditional external sclerotomy.

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.

Anaphylatoxin levels in human vitreous humor.

The complement system is involved not only in host defense against infection but also in autoimmune tissue damage. Using a radioimmunoassay, we sought to measure levels of C3a, C4a and C5a (activated complement fragments with anaphylatoxin functions) in human vitreous humor from eyes with and without vitreal inflammation. Vitreous from 11 patients with clinical evidence of vitritis (Group 2) had significantly higher levels of protein, C3a and C4a and significantly higher ratios of these anaphylatoxins to protein than vitreous from 19 patients without clinical evidence of vitritis (Group 1). The finding that not only the absolute levels of anaphylatoxins but also the ratios of anaphylatoxins to protein were significantly higher in vitreous from Group 2 than vitreous from Group 1 or normal plasma suggested that complement activation was taking place in inflamed vitreous. Because of irreversible binding to leukocytes, C5a is difficult to measure and correlate with complement activation, and we were unable to detect it in any vitreous sample.

Treatment of cytomegalovirus retinopathy with ganciclovir.

Ganciclovir is an experimental antiviral drug with activity against human cytomegalovirus (CMV). Forty patients with acquired immune deficiency syndrome (AIDS) and CMV retinopathy were treated with ganciclovir on a compassionate protocol basis. Initial treatment doses ranged from 5.0 to 14.0 mg/kg/day for 9 to 26 days. Signs of drug response were a halt to enlargement of lesions, decreased opacification of retinal tissue, and resolution of hemorrhage and vasculitis. Complete response was seen in 88% of patients and incomplete response was seen in 9%. Vision improved or remained stable in 88% of patients. Initial treatment did not eradicate live virus from the eye. To prevent reactivation of disease, 26 patients received low-dose maintenance therapy ranging from 1.5 to 7.5 mg/kg/day, once or twice daily, 3 to 7 days per week. Reactivation of disease developed for unknown reasons in 50% of patients on continuous, uninterrupted maintenance therapy for longer than 3 weeks. Reversible neutropenia, requiring cessation of treatment, developed in 30% of patients on initial treatment and in 38% of patients on maintenance therapy. Rhegmatogenous retinal detachment was a late complication in seven patients. By reducing or delaying visual loss, ganciclovir appears to be useful in the management of CMV retinopathy in patients with AIDS.

Latent nystagmus and strabismic amblyopia.

Conventional occlusion of the sound eye improved visual acuity in 11 of 12 patients with latent nystagmus and strabismic amblyopia. The successful results reported in this study are in contradiction to current views that occlusion therapy is futile or even contraindicated in patients with amblyopia and latent nystagmus.

Treatment of cytomegalovirus retinopathy in patients with acquired immunodeficiency syndrome. Use of the experimental drug 9-[2-hydroxy-1-(hydroxymethyl)ethoxymethyl]guanine.

Cytomegalovirus (CMV) retinopathy, a relentlessly progressive disease that results in permanent blindness, is the most common opportunistic infection of the eye in patients with the acquired immunodeficiency syndrome. Twenty patients with the acquired immunodeficiency syndrome with CMV retinopathy were treated with a new, experimental, antiviral drug, 9-[2-hydroxy-1-(hydroxymethyl)ethoxymethyl]guanine (BW B759U), in dosages ranging from 5.0 to 14.0 mg/kg/d for a ten- to 20-day course. In 19 patients (95%), treatment halted the progression of infection and decreased retinal opacification, hemorrhage, and vasculitis. Vision remained stable in most cases. Six patients received no additional treatment. Fourteen patients received continued treatment with a lower maintenance dosage. Retinal disease reactivated in all patients who did not receive maintenance therapy immediately after initial treatment, indicating persistence of live virus despite drug therapy. Reactivation of disease also developed in four (40%) of ten patients receiving continuous, uninterrupted maintenance therapy for longer than three weeks. Reversible neutropenia, requiring cessation of treatment, developed in five (25%) of 20 patients on initial treatment and five (36%) of 14 patients receiving maintenance therapy. Rhegmatogenous retinal detachment was a late complication in four patients. BW B759U appears to be useful in the management of CMV retinopathy by reducing or delaying visual loss.