Pars plana incisions of four patients: histopathology and electron microscopy.

The pathology of pars plana incisions of four patients is described: three with light microscopy and one with light and electron microscopy. Two eyes were removed because of choroidal melanoma, immediately and 8 days after vitrectomy and transvitreous retinal biopsy. Considerable disruption of tissues surrounding the pars plana incisions was observed. Vitreous was incarcerated in the wounds, which healed with granulation tissue. One eye was examined 4 months after vitrectomy for diabetic retinopathy and a failed pars plana filtering operation. It contained fibrovascular ingrowth from all the incisions, infiltrating the vitreous base with granulation tissue and causing vitreous haemorrhage and retinal detachment. One eye was removed 1 year after vitrectomy for anterior hyaloidal fibrovascular proliferation and early phthisis. The wound had fibrous ingrowth histologically and evidence of active fibroplasia.

Involvement of anterior chamber angle structures in disseminated histoplasmosis: report of three cases.

This study describes the involvement of anterior chamber (AC) angle structures in patients with disseminated histoplasmosis. The postmortem eyes from three patients (aged 33, 41, and 42 years, respectively) with disseminated histoplasmosis, two of whom had acquired immunodeficiency syndrome, were examined by light microscopy using hematoxylin-eosin, periodic acid-Schiff (PAS), and Gomori's methenamide silver (GMS) stains. Electron microscopy studies of the choroid were performed in one eye. Significant numbers of budding yeast forms of Histoplasma capsulatum measuring 2-5 microns in diameter were observed within the trabecular meshwork, Schlemm's canal and in the deep intrascleral plexuses. All eyes showed massive involvement of the choroidal vasculature, including the choriocapillaris. The organisms were observed freely as well as in small clusters within the cytoplasm of circulating monocytes. The vessels of the limbal conjunctiva (two eyes) and ciliary body (three eyes) contained many Histoplasma organisms. In one eye, several budding yeast were noted in an iris vessel and in occasional histiocytes within the ciliary muscle. Blood smears containing Histoplasma organisms were observed in two cases. None of the patients had an ophthalmologic examination prior to death. Involvement of the intravascular structures of the eye as well as the AC angle was observed in three patients with disseminated histoplasmosis. The fungus most likely reached the AC angle structures by direct hematogenous dissemination or via the aqueous humor by migration from vessels in the ciliary body and iris. An abnormal retrograde blood flow into the AC angle structures may have also played an important role. We suggested that the intraocular pressure be monitored in cases of suspected disseminated histoplasmosis to detect functional alterations indicative of a blockage in the outflow channels.

Screening corneas for human immunodeficiency virus type 1 proviral DNA by polymerase chain reaction.

PURPOSE: We evaluated the sensitivity of the polymerase chain reaction as a technique to directly screen potential donor corneas for human immunodeficiency virus type 1 (HIV-1) proviral DNA. METHODS: DNA from the central 8.0-mm cornea, limbal cornea, aqueous humor, and retina from 22 eyes of 11 cadavers seropositive for HIV was extracted and amplified by polymerase chain reaction using primers specific for the gag and env regions of the HIV-1 genome. The identity of amplification products was confirmed by Southern blot hybridization. RESULTS: Viral DNA was detected in four (18.2%) of 22 central corneas, one (4.5%) of 22 limbal corneas, one (6.3%) of 16 aqueous humor samples, and seven (31.8%) of 22 retinas. No correlation was noted between the presence of HIV-1 proviral DNA in samples from the central cornea and from the other tissues tested from the same eye. CONCLUSIONS: Within the limits of our assay, processing and analysis of limbal cornea, aqueous humor, and retina by polymerase chain reaction may not reliably ascertain the presence of HIV-1 in the central, transplantable cornea.

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.

Growth of the human optic disk and nerve during gestation, childhood, and early adulthood.

We measured vertical and horizontal diameters of the optic disk and retrobulbar optic nerve in eyes from 95 patients on whom autopsies were performed at the UCLA Medical Center over a 20-year period. Ages at death ranged from 4.8 months' gestation to 21.9 years. Optic disk surface area and nerve cross-sectional area were calculated for each subject by using the formula for an ellipse. Approximately 50% of the growth of the optic disk and nerve occurs by 20 weeks' gestation, and 75% by birth; 95% of the growth occurs before the age of 1 year. All optic disk and nerve measurements correlate strongly (correlations > .67; P < .0001) with subject height and globe anteroposterior diameter. We applied our results to the current understanding of optic disk and nerve development, and compared them to previous clinical and pathologic studies of optic nerve dimensions in adults and older children.

Immunocytologic findings in a case of Vogt-Koyanagi-Harada syndrome.

BACKGROUND: Vogt-Koyanagi-Harada (VKH) syndrome is a form of chronic panuveitis that often has a poor long-term visual outcome. To the authors' knowledge, there have been only two previous reports describing immunocytologic findings in the eyes of patients with VKH syndrome, all studied in relatively late stages of the disease. METHODS: The authors performed immunocytologic studies on the enucleated eyes of a patient with active VKH syndrome, using monoclonal antibodies to mononuclear subsets, major histocompatibility antigens, and viral and treponemal agents, to better understand the pathophysiologic mechanisms underlying the disease. Emulsified chorioretinal tissue also was processed for viral isolation in tissue culture and for Treponema pallidum by rabbit inoculation studies. RESULTS: The dense uveal infiltrates in active VKH syndrome are composed predominantly of T lymphocytes and HLA-DR+ macrophages. Scattered T cells and plasma cells were present in the retina. In addition, nondendritic-appearing CD1 (Leu-6) positive cells were localized in the choroid, in close proximity to choroidal melanocytes. No microbial agents were identified. CONCLUSION: Whereas the etiology of the VKH syndrome remains an enigma, the authors' immunocytologic findings are consistent with a T-cell-mediated disorder. In demonstrating CD1 (Leu-6) positive cells in the infiltrates, the authors propose a potential role for these cells in the etiology of VKH syndrome.

Mycobacterium fortuitum keratitis. Clinicopathologic correlates and corticosteroid effects in an animal model.

Mycobacterium fortuitum keratitis is an indolent infection of traumatized corneas in humans. To study this disorder in an animal model, 10(4) M fortuitum organisms (10 microliters) were inoculated into the stroma of both corneas of 16 New Zealand albino rabbits. Eight of the rabbits were also given bilateral subconjunctival injections of methylprednisolone acetate (20 mg in 0.5 ml) at the time of inoculation. Two corticosteroid-treated and two untreated rabbits were selected each week after inoculation for histopathological examination and quantitative cultures. Corneal lesions in corticosteroid-treated eyes were characterized clinically by indolent ulcerations and satellite lesions that slowly enlarged; on histopathologic examination at each week, acute inflammation and microorganisms were consistently present. Corneal lesions in untreated eyes were characterized clinically by small infiltrates that progressed little over time; at weeks 1 and 2, light microscopic examination showed intrastromal granulomatous and/or mixed acute and chronic inflammation with focal intrastromal necrosis, but at weeks 3 and 4 there was no evidence of active disease. Organisms could not be identified microscopically in corneas of any untreated rabbits. Mean values for quantitative cultures of corneas were higher in corticosteroid-treated rabbits after week 1, although standard deviations were large. These results suggest that M fortuitum keratitis in rabbits is made worse by corticosteroid use. Clinical and histopathologic changes were compared with human disease and found to be similar in corticosteroid-treated rabbits.

Intravitreous granulation tissue and retinal detachment following pars plana injection for cytomegalovirus retinopathy.

Recently, the pars plana route of injection has been used to administer drugs for the treatment of severe intraocular infections. We observed a complication of this method in a patient with AIDS and cytomegalovirus (CMV) retinopathy.

Immunopathologic features of retinal lesions in multiple sclerosis.

To further characterize the nature of retinal periphlebitis and retinitis in multiple sclerosis, immunoperoxidase studies were performed on retinal tissue from multiple sclerosis patients at autopsy. Antibodies against myelin basic protein stained the optic nerve but not the retina. Both normal and multiple sclerosis retinas showed staining of Müller cells with Leu-7 (a monoclonal antibody that cross-reacts with myelin associated glycoprotein and natural killer cells). Nerve fiber bundles of the optic nerve in cases with multiple sclerosis and controls also showed staining with Leu-7 antibody. Tissue-bound IgG was demonstrated on retinal ganglion cells in six of seven multiple sclerosis cases but not in controls.

Ultrastructural and immunohistochemical features of coronal adenomas.

We studied by electron microscopy three coronal adenomas discovered incidentally in eyes removed surgically. Tumor cells displayed prominent intercellular interdigitations with numerous desmosomes, mitochondria, abundant rough endoplasmic reticulum, and nuclei with membrane infoldings and a granular chromatin pattern. In these characteristics, the tumor cells were identical to nonpigmented ciliary epithelium of the ciliary processes. These growths contained abundant extracellular material, which showed a dimorphic pattern of complex reduplicated basal lamina and granular areas without structure. Immunohistochemical studies on formalin-fixed, paraffin-embedded coronal adenomas demonstrated type IV collagen and laminin in the extracellular material. These findings confirm that coronal adenomas develop from nonpigmented ciliary epithelium and that the extracellular material of these tumors contains components normally present in basement membranes.

Necrotizing retinopathy after intraocular inoculation of murine cytomegalovirus in immunosuppressed adult mice.

A light microscopic study was done to investigate retinal changes in healthy and immunosuppressed mice after intraocular inoculation of murine cytomegalovirus (MCMV). A 0.01-ml inoculum containing 10(5) plaque-forming units of MCMV was placed behind the lens in 138 4-week-old Swiss Webster mice. Ninety-eight mice were immunosuppressed with 0.2 mg/g of cyclophosphamide given intraperitoneally at the time of inoculation and 0.1 mg/g of cyclophosphamide every 5 days thereafter. Selected eyes were examined on postinoculation days 5, 10, 15, and 16-20. Evidence of viral infection was most prominent in uveal tissue. Uveal infection developed whether or not animals received cyclophosphamide, but retinal necrosis developed only in immunosuppressed mice. Focal retinal necrosis, primarily involving the outer retinal layers and retinal pigment epithelium, was first observed in an eye examined on day 10. Retinopathy from MCMV was present in three of five eyes (60%) examined on day 15, and in six of 16 eyes (37.5%) examined between days 16-20. Retinal disease was characterized by full-thickness retinal necrosis, scattered cytomegalic cells, intranuclear and intracytoplasmic viral inclusions, and acute and chronic inflammation. These results indicate that MCMV can produce a necrotizing retinopathy in mice and that immunosuppression facilitates infection. Although ocular MCMV infection in immunosuppressed adult mice is a potential model for study of human CMV retinopathy, many differences exist between human CMV and MCMV and between the ocular diseases they produce.

HMB-45 antibody reactivity in pigmented lesions of the conjunctiva.

Conjunctival pigmented lesions, including ten compound nevi, three subepithelial nevi, two acquired melanoses, and six melanomas, were examined histologically and immunohistochemically to determine the specificity of mouse monoclonal HMB-45 antibody for these lesions. Eleven of 13 nevi, two of two acquired melanoses, and six of six melanomas stained with this antibody. Conjunctival melanomas showed intense and diffuse cytoplasmic staining; compound nevi and subepithelial nevi showed less intense but diffuse reaction. There was strong staining in melanocytic cells at the junction of the epithelium and substantia propria in compound nevi and acquired melanoses. Unlike skin nevi, conjunctival nevi show HMB-45 reactivity in their stromal components. Immunoreactivity to HMB-45 does not distinguish benign from atypical or malignant melanocytic lesions of the conjunctiva.

Infectious crystalline keratopathy in a neonatal infant.

Bilateral white crystalline opacities of the central corneas were found at autopsy in the eyes of a 17-day-old girl with Turner's Syndrome. Corticosteroid therapy had not been used. Histopathologic and electron microscopic evaluation revealed clusters of gram-negative rods between relatively intact stromal lamellae. Inflammation was mild and restricted to the limbus and peripheral cornea. This case represents an unusual presentation of an infectious crystalline keratopathy.

Traumatic neuroma of the eyelid associated with ptosis.

A 17-year-old boy presented with persistent swelling and ptosis of the eyelid after blunt injury. Histologic examination revealed a clinically unsuspected traumatic neuroma. Ptosis and the traumatic neuroma persisted despite two eyelid operations. Traumatic neuroma is rare after blunt trauma; it has not been previously reported in the eyelid. It is important to identify this lesion because complete excision may help to prevent recurrence.

Keratinizing corneal intraepithelial neoplasia.

Corneal intraepithelial neoplasia (CIN) is the term applied by some authors to the spectrum of disease ranging from mild dysplasia to carcinoma in situ. Such lesions usually are associated with dysplastic or neoplastic processes at the limbus or adjacent conjunctiva; isolated corneal dysplasia is rare. Clinically, CIN appears as a geographic, gray, translucent thickening of the epithelium with fimbriated or scalloped borders and lesions often contain scattered white dots. We report a case of intraepithelial neoplasia limited to the cornea that had the unusual clinical appearance of a white plaque, which prompted the misdiagnosis of a calcific scar. Histopathologic examination of the debrided tissue revealed intraepithelial neoplasia and marked hyperkeratosis as the cause of the opacification.

Dual infection of retina with human immunodeficiency virus type 1 and cytomegalovirus.

We examined retinal tissue from eight human immunodeficiency virus type 1 (HIV-1) seropositive patients with acquired immunodeficiency syndrome (AIDS) or AIDS-related complex for evidence of dual infection with HIV-1 and cytomegalovirus. Culture demonstrated simultaneous infection with HIV-1 and cytomegalovirus in two of 13 retinal specimens. This was confirmed by both immunofluorescence and immunohistochemical staining. Moreover, coinfection of individual cells with cytomegalovirus and HIV-1 was observed by immunohistochemical staining. Infection of retina with cytomegalovirus or HIV-1 alone occurred in one and six of the 13 retinal specimens, respectively. HIV-1 antigens were present on scattered cells in all layers of the retina and on retinal vascular endothelium. HIV-1 was isolated from retinal tissue derived from eyes both with and without gross ocular lesions. Cytomegalovirus antigens were found in all layers of the retina, but not on vascular endothelial cells. The atypically rapid clinical progression of retinitis in one of the patients with dual HIV-1 and cytomegalovirus infection suggests the possibility that interactions between these two viruses may influence retinal disease in patients with AIDS.