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Biomedical subjects

W R Freeman

Publications and source records attributed to W R Freeman.

At least 109 records · Page 6Linked to original sources

Clinicopathologic correlations in acute retinal necrosis caused by herpes simplex virus type 2.

The acute retinal necrosis syndrome is a rapidly progressive and potentially devastating disease. A case of acute retinal necrosis developed in an immunocompetent man, Presumably due to the stress, trauma, or immunomodulation related to a craniotomy for a parasellar craniopharyngioma. Vitrectomy and endoretinal biopsy were performed. Polymerase chain reaction studies of the vitreous revealed herpes simplex virus type 2 as the cause, which has not been previously well documented. Results of cerebrospinal fluid antibody studies were also consistent with the diagnosis. Results of cytology and histopathologic examination demonstrated extensive retinal destruction and mononuclear cell infiltration. Sloughing of the inner retina was evidenced by the presence of retinal vascular remnants in the vitreous cytology specimen. As is characteristic of this disease, the visual outcome of this patient was poor.

Adult↗

Optic neuropathy preceding acute retinal necrosis in acquired immunodeficiency syndrome.

OBJECTIVE: To describe the clinical course of varicella-zoster optic neuropathy preceding acute retinal necrosis in patients with acquired immunodeficiency syndrome. DESIGN: Case series. SETTING: Two tertiary care centers in San Diego, Calif, and London, England. PATIENTS: Three human immunodeficiency virus-positive men with previous cutaneous zoster infection, optic neuropathy, and necrotizing retinitis. RESULTS: All patients had an episode of zoster dermatitis treated with acyclovir. Visual loss consistent with an optic neuropathy ensued, followed by typical herpetic retinitis. The cause of visual loss was not suspected to be varicella-zoster until after the retinitis occurred. Despite aggressive medical treatment, 4 of 6 eyes progressed to retinal detachment. CONCLUSIONS: Varicella-zoster may cause an optic neuropathy in patients with acquired immunodeficiency syndrome, especially in those with previous shingles. A high index of suspicion is necessary to establish the diagnosis and begin early antizoster treatment.

AIDS-Related Opportunistic Infections↗

Prospective randomized trial of vitrectomy or observation for stage 2 macular holes. Vitrectomy for Macular Hole Study Group.

PURPOSE: To determine the risks and benefits of vitrectomy surgery in eyes with stage 2 macular holes. METHODS: A multicentered, controlled, randomized clinical trial was performed with participation of 16 community and university-based ophthalmology clinics. Thirty-six eyes with stage 2 macular holes and 12 months of follow-up were studied. Pars plana vitrectomy with separation of the posterior hyaloid membrane and intraocular injection of perfluoropropane (C3F8) was followed by postoperative face-down positioning for two weeks. This protocol was compared with observation alone. Outcome variables included anatomic closure of the macular hole, macular hole size, and four standardized measures of vision. RESULTS: At 12 months, 15 (71%) of 21 eyes randomly assigned to observation progressed to stages 3 or 4, compared with three (20%) of 15 eyes randomly assigned to surgery (P < .006). Compared with eyes randomly assigned to observation, eyes randomly assigned to surgery had significantly smaller hole diameters (P < .01) and significantly better visual acuity outcomes, as measured by the Word Reading (P = .02) and Potential Acuity Meter (P = .002) charts. No significant differences were found for the Early Treatment Diabetic Retinopathy Study chart and Contrast Sensitivity test. CONCLUSION: Compared with observation alone, surgical intervention in stage 2 macular holes resulted in a significantly lower incidence of hole enlargement and appeared to be associated with better outcome in some measures of visual acuity.

Aged↗

Correlation between intraocular pressure and CD4+ T-lymphocyte counts in patients with human immunodeficiency virus with and without cytomegalovirus retinitis.

PURPOSE: To determine the intraocular pressure in patients with human immunodeficiency virus (HIV) with and without cytomegalovirus retinitis, and to correlate intraocular pressure with CD4+ T-lymphocyte count and the presence, extent, and activity of cytomegalovirus retinitis. METHODS: Intraocular pressure was measured with calibrated Goldmann applanation tonometers in two groups of patients. Group A included 84 patients with HIV (120 eyes) with cytomegalovirus retinitis, and Group B included 110 patients with HIV (183 eyes) without cytomegalovirus retinitis. Thirty-three patients without HIV (66 eyes) were included as a control group. Step-wise regression analysis of intraocular pressure included correlation with cytomegalovirus retinitis (presence, extent, and activity), CD4+ T-lymphocyte count, age, and gender. RESULTS: The mean intraocular pressure was 9.8 mm Hg in Group A, 12.6 mm Hg in Group B, and 16.1 mm Hg in the control group. All three groups were statistically different from each other when intraocular pressure was compared (P < .0001). Step-wise regression showed that low CD4+ T-lymphocyte count (r2 = .20; P < .0001) and extent of cytomegalovirus retinitis (r2 = .08; P = .007) both correlated to low intraocular pressure. CONCLUSION: Intraocular pressure is lower than normal in patients with HIV. Decreased CD4+ T-lymphocyte count is the major association with low intraocular pressure (20% of the effect); extent of cytomegalovirus retinitis accounts for 8% of the effect. Knowledge of the normal range of intraocular pressure in patients with HIV will be important to the understanding and treatment of glaucoma and other disorders or treatments affecting intraocular pressure.

Adult↗

Visual field loss in HIV-positive patients without infectious retinopathy.

PURPOSE: To determine the extent of vision loss in a cross-sectional study of HIV-positive individuals who had no infectious retinopathy. METHODS: Visual field loss was determined by computerized achromatic automated perimetry and short-wavelength automated perimetry in both eyes in 65 HIV-positive individuals without infectious retinopathy and in one randomly selected eye each in 57 age-matched normal controls. Results were analyzed using the global index of mean defect and the Glaucoma Hemifield Test, and significance was determined through analysis of variance, chi-square, and Tukey-Kramer tests. RESULTS: We found that HIV-positive patients, compared with age-matched HIV-negative controls, demonstrated significant (at least P < .01) localized defects as well as an increased mean defect. The HIV-positive patients also had a significantly greater number of defective points, especially on short-wavelength automated perimetry, even while ophthalmoscopic examination and fundus photographs suggested that the retinas were normal. CONCLUSIONS: There is a significant loss of visual function in HIV-positive individuals that is not the result of infectious retinopathies. The finding by short-wavelength perimetry of more severe defects suggests that the vision defects are not caused by attentional or other suprachiasmatic problems because the neurologic difficulty of both achromatic and short-wavelength perimetry is similar. The effects of this vision loss on the daily living and occupational tasks of this population require further study.

Adult↗

Intravitreal cidofovir for the maintenance treatment of cytomegalovirus retinitis.

PURPOSE: To evaluate the efficacy and safety of multiple intravitreal cidofovir (HPMPC) injections given every 5 to 6 weeks for the maintenance treatment of cytomegalovirus (CMV) retinitis. METHODS: A prospective consecutive case series of 53 eyes in 35 patients with acquired immune deficiency syndrome and CMV retinitis was treated with maintenance intravitreal injections of cidofovir (20 micrograms) at one referral center between April 1994 and September 1995. Twenty-four eyes received intravitreal cidofovir as their initial treatment for CMV retinitis (group A), and 29 eyes previously had received systemic therapy (group B). None of the patients in either group received systemic anti-CMV therapy at any time during the study period. Progression of retinitis was the primary end point. RESULTS: All eyes with active retinitis healed in response to treatment. None of the 24 eyes in group A demonstrated any progression during the study period. Four (14%) of the 29 eyes in group B had one episode each of retinitis progression (mean follow-up, 15 weeks; range, 0-58 weeks). In 1 (1.9%) of the 53 eyes, a retinal detachment developed. A mild iritis was observed after 14% of injections, which were prophylaxed with oral probenecid. Irreversible visually significant hypotony developed in two eyes (3.8%). CONCLUSION: Treatment and subsequent maintenance therapy of CMV retinitis with 20 micrograms intravitreally injected cidofovir, given at 5- to 6-week intervals, is highly effective, with only rare episodes of re-activation and progression.

AIDS-Related Opportunistic Infections↗

Posterior vitreoschisis. An echographic finding in proliferative diabetic retinopathy.

PURPOSE: To describe the echographic characteristics of splitting the outer posterior cortical vitreous in patients with proliferative diabetic retinopathy and vitreous hemorrhage. METHODS: The authors retrospectively reviewed the echographic findings in 270 patients who were evaluated at the Doheny Eye Institute between January 1983 to December 1989 for proliferative diabetic retinopathy and vitreous hemorrhage. None of the eyes had undergone pars plana vitrectomy before echographic examination. RESULTS: Forty-five patients (17%) had echographic evidence of splitting of the outer posterior vitreous cortex, a finding the authors have termed posterior vitreoschisis. In all patients, differentiation of the posterior vitreoschisis from a true posterior hyaloid detachment was possible, either on the initial or on serial echographic examination, by the separate detachment of the inner wall of the vitreoschisis cavity and the true posterior hyaloid from the retinal surface. The vitreoschisis cavities often were found to contain unclotted blood. In some eyes, the inner wall of the vitreoschisis cavity was adherent to the apex of the most highly elevated area of traction retinal detachment, suggesting that posterior vitreoschisis may itself result in clinically significant vitreoretinal traction, independent of the presence or extent of true posterior hyaloid separation. CONCLUSIONS: The authors' finding suggest that spontaneous splitting of the outer posterior vitreous cortex may occur in patients with proliferative diabetic retinopathy and vitreous hemorrhage, which may mimic a true posterior cortical vitreous detachment on echographic examination. Preoperative recognition of posterior vitreoschisis may be important in the surgical management of these patients.

Adult↗

Liposome-encapsulated (S)-1-(3-hydroxy-2-phosphonylmethoxypropyl)cytosine for long-acting therapy of viral retinitis.

The effect of liposome-encapsulated (S)-1-(3-hydroxy-2-phosphonylmethoxypropyl)cytosine (HPMPC; cidofovir) was evaluated as prophylaxis in a rabbit model of experimentally induced retinitis caused by preretinal inoculation of herpes simplex virus type 1 (HSV-1). Cidofovir (100 micrograms) in liposomes (0.1 mL) was injected intravitreally 10-120 days before retinal inoculation with HSV-1. Twenty-two of 26 eyes pretreated with liposome-encapsulated cidofovir 10-60 days before HSV-1 inoculation were protected from experimentally induced retinitis, and 2 of 5 eyes pretreated 120 days before inoculation were protected. Intravitreal levels of cidofovir were low (0.7 microgram/mL) but detectable 120 days after injection. One 100-micrograms intravitreal injection of liposome-encapsulated cidofovir appears to have a remarkably potent and prolonged (up to 4 months) antiviral effect in this experimental model of HSV-1 retinitis. Since HPMPC is even more potent against cytomegalovirus than HSV-1, liposome-encapsulated cidofovir may prove to be effective local therapy for AIDS patients with cytomegalovirus retinitis.

Animals↗

Polyradiculopathy associated with ganciclovir-resistant cytomegalovirus in an AIDS patient: phenotypic and genotypic characterization of sequential virus isolates.

To investigate the role of antiviral drug resistance in cytomegalovirus (CMV) disease progression, CMV cultured from an AIDS patient who developed progressive CMV disease despite continual anti- CMV treatment was characterized. In 7 CMV isolates, 1 ganciclovir-resistant strain predominated. Ganciclovir-resistant CMV, containing a UL97 mutation, was cultured from blood and urine before clinical indication of CMV central nervous system (CNS) disease, suggesting that the development of ganciclovir resistance preceded the dissemination of CMV to the CNS. Quantitative competitive polymerase chain reaction indicated that the isolation of ganciclovir-resistant CMV was concurrent with increased CMV DNA in plasma. The results suggest that antiviral resistance should be considered when selecting therapy for CMV CNS disease that develops in patients receiving treatment for CMV retinitis. In addition, plasma CMV DNA in AIDS patients receiving anti-CMV therapy may be a useful marker of disease progression and antiviral resistance.

AIDS-Related Opportunistic Infections↗

Use of perflubron as a new temporary vitreous substitute and manipulation agent for vitreoretinal surgery. Wills Eye Hospital Perflubron Study Group.

PURPOSE: The authors determine the intraocular tolerance of a new widely used liquid perfluorocarbon, perfluoroctylbromide (perflubron). METHODS: Pars plana vitrectomy was performed on 54 eyes of 54 patients with vitreoretinal disorders at three centers. Diagnoses included giant retinal tears, proliferative vitreoretinopathy, and dislocated intraocular and crystalline lenses. At the conclusion of the vitrectomy, perflubron was removed. RESULTS: Perflubron was efficacious for vitreoretinal manipulation. Of the 45 eyes with retinal detachment, 23 (51.1%) of the retinas were reattached after a single surgery; redetachment occurred in 22 (48.9%) after the initial procedure, and further surgery was necessary to reattach the retina. Final retinal reattachment was achieved in 40 (88.9%) eyes. Mean visual acuity improvement was six lines (P < 0.0019). Visualization of the water/perfluorocarbon interface was good. There was no evidence of adverse effects from perflubron on the retina, lens, or anterior segment. CONCLUSION: Findings indicate that perflubron is safe for temporary intraoperative use intravitreally. The absence of adverse effects is consistent with the properties of perflubron that our group has studied in the eyes of animals and in other uses in human patients.

Adolescent↗

Polymerase chain reaction detection of cytomegalovirus and human immunodeficiency virus-1 in the retina of patients with acquired immune deficiency syndrome with and without cotton-wool spots.

PURPOSE: The authors determine the association, if any, between detection of human cytomegalovirus (CMV) and human immunodeficiency virus (HIV) nucleic acids and retinal lesions in patients with acquired immune deficiency syndrome. METHODS: Postmortem eyes were examined with a dissecting microscope and light microscopy. Retinal cotton-wool spots (CWS) were removed using a clean touch punch biopsy technique. Equivalent amounts of retinal tissue from the posterior pole of the retina not affected by CWS and from the retinal periphery also were studied. Polymerase chain reaction (PCR) detection of retinal cellular DNA (GA3PD gene), human CMV DNA (major immediate early gene), and HIV (gag gene) was performed using ethidium bromide and liquid hybridization detection. RESULTS: Ninety percent of CWS were positive for CMV DNA versus 22% of peripheral retinal biopsies (P < 0.025). Liquid hybridization showed similar results. Analysis of lesions in which results of both tests were positive (ethidium and liquid hybridization) versus lesions in which results of either test were negative also showed a strong association between CWS and CMV, but not HIV nucleic acids (P < 0.02). Studies of HIV showed no association between retinal CWS lesions and HIV nucleic acid; with liquid hybridization HIV, RNA was detected equally at low levels in all areas. CONCLUSION: There is a statistically significant association between the presence of human CMV nucleic acids and retinal CWS detected by PCR. There is a low level presence of HIV in the retinal tissue studied that is only detectable using liquid hybridization techniques and is not associated with a particular area or lesions in the retina; this may represent detection of HIV in blood. The presence of CMV in areas of retinal CWS may have implications for their pathogenesis, but further study is necessary because other explanations are possible.

AIDS-Related Opportunistic Infections↗

Clinical versus fundus photographic evaluation of the status of cytomegalovirus retinitis in AIDS patients.

PURPOSE: To evaluate the accuracy of clinical examinations and serial fundus photographic readings in determining the response of cytomegalovirus retinitis to antiviral therapy in patients with acquired immune deficiency syndrome. METHODS: Fifty two consecutive patients with cytomegalovirus retinitis who were prospectively evaluated over a 30-month period for a minimum of 6 months (or until death) were included in this study. There was a total of 708 patients visits. The clinical evaluations included indirect ophthalmoscopy, fundus drawings, 60 degrees fundus photographs, and a comparison of the photographs with those of the previous visit. The fundus photographs were reevaluated in a blinded fashion. Cytomegalovirus retinitis was classified as active (progression of border since last examination) intermediate (border activity without progression), healed (no activity since last visit), or normal (no retinitis). RESULTS: Using the photographic data as the measure of cytomegalovirus retinitis activity, the sensitivity and specificity of clinical assessments were determined. The sensitivity and specificity of clinical versus photographic evaluations varied with retinitis status. In healed retinitis the sensitivity of the clinical examination was 98%, and the specificity was 83%. In cases of border opacification without progression the sensitivity was 80%, and the specificity was 96%. In cases of clinically active retinitis the sensitivity was 63% with a specificity of 100%. Clinical detection of active retinitis and border opacification without progression was reduced when potential problems were present that made visualization of the retinitis border difficult, such as smoldering retinitis, progressive retinal destruction without border opacification, poor media, or fundus pigmentation. CONCLUSIONS: Progressive retinal destruction and visual loss can occur in patients with cytomegalovirus retinitis despite antiviral therapy. Examining the patient through indirect ophthalmoscopy only can result in failure to detect subtle changes.

AIDS-Related Opportunistic Infections↗

The Agar sandwich technique for retinal biopsy processing.

BACKGROUND: The authors developed an agar sandwich technique for retinal biopsy processing. This tissue agar embedding technique allows for a rapid and reliable method to handle and transport retinal biopsies from the operative field to the histology laboratory. METHODS: Biopsies from rabbit retinas infected with herpes simplex virus, epiretinal membranes from patients with macular pucker, and retinas from patients with acute retinal necrosis were studied. Each retinal biopsy was fixed, mounted on an agar disc, and covered with liquid agar. Light microscopy, electron microscopy, immunocytochemistry, and polymerase chain reaction were employed on the agar-embedded tissue. RESULTS: The tissues remained mounted in the agar sandwich and maintained their orientation throughout the processing. The morphologic integrity, histologic characteristics, antigenic properties, and DNA quality all were preserved using the agar sandwich technique. CONCLUSION: The agar sandwich technique is an efficient and simple technique for handling small biopsy specimens that require various analyses.

Agar↗

Pattern electroretinograms and visual evoked potentials in HIV infection: evidence of asymptomatic retinal and postretinal impairment in the absence of infectious retinopathy.

Retinal microangiopathy associated with HIV infection is usually asymptomatic and escapes detection unless funduscopic examination is performed when evanescent cotton-wool spots are present. The aim of this study was to assess retinal and optic nerve/retrochiasmal function in HIV infection by means of electrophysiologic techniques that are sensitive to the detection of subclinical visual impairment. We studied transient and steady state pattern electroretinograms grams (PERGs) and pattern-reversal visual evoked potentials (PVEPs) in 21 HIV-negative controls and 33 HIV-positive subjects (16 with CD4 > or = 200/mL and 17 with CD4 < 200/mL) without visual symptoms or infectious retinopathy. HIV-positive subjects with CD4 > or = 200/mL had reduced amplitude of the transient PERG P1 potential, but no other latency or amplitude abnormalities. The HIV-positive group with CD4 < 200/mL had reduced P1 transient PERG amplitude, as well as latency delay of the transient PVEP. These findings suggest that HIV infection is associated with subclinical retinopathy and that, when severe immunosuppression occurs, both retinopathy and optic nerve/retrochiasmal dysfunction are present. Transient PERGs are more sensitive measures of visual system disease in HIV infection than are steady state responses.

Adolescent↗

Rhegmatogenous retinal detachments in HIV-positive patients with ocular syphilis.

The purpose of this study is to report retinal manifestations of lues in human immunodeficiency virus (HIV)-positive patients and to suggest a method for treatment of rhegmatogenous retinal detachments in these patients. Two HIV-positive patients with bilateral retinitis were examined and treated at the authors' institution for a period of 14 months. Ocular syphilis was diagnosed clinically, confirmed by cerebrospinal fluid serologic testing, and treated with intravenous penicillin. Both patients experienced bilateral rhegmatogenous retinal detachments complicated by proliferative vitreoretinopathy after resolution of the active retinitis. All four eyes underwent surgical repair with trans pars plana vitrectomy, epiretinal membrane delamination, gas-fluid exchange, endolaser, scleral buckle, and silicone oil instillation. The recognition of ocular syphilis as a cause of retinal detachment in HIV-positive patients is important. Prompt intervention with the appropriate medical and surgical treatments may result in the preservation of vision in these patients.

Adult↗

The predictive value of cytomegalovirus retinitis for cytomegalovirus encephalitis in acquired immunodeficiency syndrome.

Cytomegalovirus (CMV) infection of the brain, optic nerves, and retinas from 47 consecutive autopsies of patients with acquired immunodeficiency syndrome (AIDS) were examined. Immunocytochemistry demonstrated CMV infection in 11 (23%) brains, two (2%) of 94 optic nerves, and 38 (40%) of 94 retinas. Ten (91%) of 11 patients with CMV encephalitis had concurrent retinitis. While 10 (42%) of 24 patients with CMV retinitis had CMV encephalitis, when the retinitis included the peripapillary region, 75% had encephalitis. Usually, the optic nerve parenchyma was not infected histologically despite extensive peripapillary retinitis. The strength of these associations suggests that CMV retinitis defines a group of patients with AIDS at risk for development of CMV encephalitis (relative risk, 9.5), particularly when the retinitis involves the peripapillary region (relative risk, 13). Furthermore, in patients with AIDS without CMV retinitis, central nervous system symptoms are unlikely to be attributable to CMV encephalitis.

AIDS-Related Opportunistic Infections↗