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Biomedical subjects

W R Freeman

Publications and source records attributed to W R Freeman.

At least 73 records · Page 4Linked to original sources
PubMed1999

Neuropsychological impairment-associated visual field deficits in HIV infection. HNRC Group. HIV Neurobehavioral Research Center.

PURPOSE: To examine the relationship between loss in peripheral visual sensitivity and neuropsychological functioning in seropositive patients with human immunodeficiency virus (HIV) without infectious retinopathy. METHODS: Subjects carefully screened for retinal disease and well-matched across demographic and medical variables were grouped according to normal (perimetry-nl) versus abnormal (perimetry-abnl) performance on achromatic automated perimetry and short-wavelength automated perimetry, standard clinical ophthalmologic measures of visual function. All subjects completed a detailed neuropsychological test battery and were classified as impaired or unimpaired, globally and across eight neurocognitive domains. Subjects were also classified according to whether they met diagnostic criteria for minor cognitive/motor disorder (MCMD) or HIV-associated dementia (HAD). RESULTS: Visual field loss was associated with lower performance in the abstraction, perceptual-motor, learning, and motor domains. Significant group differences were also found on numerous individual neuropsychological tests. Based on clinical ratings, we found deficits in learning and motor functioning. No perimetry-nl subjects met criteria for MCMD or HAD, whereas 32% of perimetry-abnl subjects met diagnostic criteria for syndromic cognitive disorders (five MCMD and one HAD). In a subset of subjects who underwent a lumbar puncture, there was a trend for the perimetry-abnl group to have a higher concentration of beta2 microglobulin, a marker for central nervous system immune activation. CONCLUSIONS: These results suggest that in some HIV-infected people reduced visual function may be caused by nonretinal disease, and perimetry may present a sensitive measure of HIV-related brain dysfunction.

Adult↗
PubMed1998

Imaging the microvasculature of choroidal melanomas with confocal indocyanine green scanning laser ophthalmoscopy.

OBJECTIVE: To image the microvasculature of choroidal melanoma with a new confocal scanning laser ophthalmoscope. METHODS: Eighteen consecutive patients, each with a unilateral choroidal melanoma, were examined prospectively. Indocyanine green angiography was performed with a new confocal scanning laser ophthalmoscope that enabled serial optical sectioning through the tumor. Two additional patients were studied with indocyanine green angiography and confocal scanning laser ophthalmoscopy just before enucleation for posterior choroidal melanomas. The histologic identification of microvasculature patterns was compared with the angiograms for these patients. RESULTS: In the series of 18 patients, 16 (89%) indocyanine green angiograms with optical sectioning revealed tubular structures within the melanoma that were identified as tumor vessels based on their angiographic appearance. The microvasculature patterns identified by indocyanine green angiography correlated well with the histologic appearance of these microvasculature patterns in both patients for whom histologic verification was available. CONCLUSIONS: This preliminary study suggests that indocyanine green angiography with confocal scanning laser ophthalmoscopy images the microvasculature of choroidal melanomas and may be capable of detecting microvasculature patterns that have been shown to be prognostically significant from histopathological studies.

Adult↗
PubMed1998

Immune recovery vitritis associated with inactive cytomegalovirus retinitis: a new syndrome.

OBJECTIVE: To describe a syndrome of posterior segment intraocular inflammation that causes visual loss in patients with acquired immunodeficiency syndrome and cytomegalovirus retinitis. This syndrome was associated with immune recovery mediated by combination antiretroviral treatment including protease inhibitors. DESIGN: A case-control study at 2 university medical centers. PARTICIPANTS: One hundred thirty patients with acquired immunodeficiency syndrome and cytomegalovirus retinitis were examined at 2 medical centers for 15 months. In addition, the medical records of 509 patients examined at 1 center for 11 years before the initiation of protease inhibitor therapy were analyzed retrospectively. RESULTS: Five patients with symptomatic vitritis and papillitis with cystoid macular edema or epiretinal membrane formation were documented. In each patient there was inactive cytomegalovirus retinitis that had not caused visual decrease before the onset of inflammation. All patients had elevated CD4+ T lymphocyte levels (median increase, 86x10(6)/L [86 cells/mm3]) after combination treatment including protease inhibitors. Two patients with cystoid macular edema were treated with corticosteroids and had resolution of the cystoid macular edema and an increase in visual acuity without reactivation of the retinitis. Retrospective analysis failed to disclose similar patients with intraocular inflammation in the era before the introduction of protease inhibitors. CONCLUSIONS: This newly described syndrome of posterior segment inflammation related to cytomegalovirus retinitis is a cause of visual morbidity in patients with acquired immunodeficiency syndrome. It is associated with increased immune competence as a result of combined antiretroviral treatment with protease inhibitors and may be amenable to corticosteroid therapy without reactivation of retinitis.

AIDS-Related Opportunistic Infections↗
PubMed1998

Clinical failure of CMV retinitis with intravitreal cidofovir is associated with antiviral resistance.

OBJECTIVES: To determine the incidence of clinical resistance to intraocular cidofovir injection for treatment of acquired immunodeficiency syndrome (AIDS)-related cytomegalovirus (CMV) retinitis, and to identify virologic features associated with cidofovir treatment failure. PATIENTS AND METHODS: Clinical resistance to intravitreal cidofovir was examined in 64 patients with CMV retinitis who received at least 1 injection of 20 pg of cidofovir. Histopathologic examination, culture, and polymerase chain reaction were used to detect CMV in ocular specimens. Antiviral resistance was assessed by plaque reduction assay and DNA sequencing. RESULTS: Clinical resistance to intravitreal cidofovir injections was identified in 3 patients (5%) and was associated with prior oral ganciclovir or intravenous cidofovir use. Ganciclovir- and cidofovir-resistant CMV isolates were cultured from 2 patients and harbored resistance-associated mutations in the UL97 and polymerase genes. Resistance mutations were also detected by direct analysis of vitreous. In 1 patient, different resistance mutations were identified in ocular vs extraocular CMV strains. CONCLUSIONS: Clinical failure of intravitreal cidofovir occurs infrequently, but may be associated with cidofovir-resistant CMV selected by prior ganciclovir or cidofovir treatment. Ocular CMV disease can result from a localized infection with a resistant CMV strain, and antiviral resistance may develop at a local site of infection independently from resistance that develops systemically.

AIDS-Related Opportunistic Infections↗
PubMed1998

Simultaneous indocyanine green and fluorescein angiography using a confocal scanning laser ophthalmoscope.

BACKGROUND: Fluorescein and indocyanine green (ICG) angiography are both useful in the diagnosis and treatment of many retinal diseases. In some cases, both tests must be performed for diagnosis and treatment; however, performing both is time-consuming and may require multiple injections. METHODS: We designed a compact digital confocal scanning laser ophthalmoscope to perform true simultaneous fluorescein and ICG angiography. We report our experience using the instrument to perform 169 angiograms in 117 patients. RESULTS: There were no unexpected adverse effects from mixing the dyes and administering them in 1 injection. An entire examination, including fundus photography, fluorescein angiography, and ICG angiography, could be performed in 45 minutes. It was possible to study differences in fluorescein patterns by comparing identically timed frames and to find cases in which ICG or fluorescein was optimal in visualizing retinal and subretinal structures. Confocal optical sections in the depth (z) dimension allowed viewing in different planes. It was possible to overlay ICG and fluorescein images or compare them side-by-side using a linked cursor. Digital transmission of the images was also performed. CONCLUSIONS: Simultaneous ICG and fluorescein angiography can be performed rapidly, safely, and conveniently. The availability of simultaneous angiography will allow critical determination of the relative advantages and disadvantages of both types of angiography.

Choroid↗
PubMed1998

Retinal blood flow measurements in branch retinal vein occlusion using scanning laser Doppler flowmetry.

PURPOSE: To determine capillary blood flow measurements in eyes with branch retinal vein occlusion using a scanning laser Doppler flowmeter. METHODS: Retinal capillary blood flow in branch retinal vein occlusion areas and corresponding ipsilateral nonbranch retinal vein occlusion areas, 11 equivalent areas of the contralateral fellow eye of 12 consecutive untreated branch retinal vein occlusion patients, and 16 eyes of 11 age-matched normal control subjects were measured with scanning laser Doppler flowmetry. A template consisting of eight squares, each with a field of 100 x 100 microm (10 x 10 pixel) with space interval of 500 microm equidistant horizontally and vertically was used to obtain blood flow measurements in all subjects. Mean blood volume, flow, and velocity were obtained by averaging the mean values measured in each field. We avoided measurement over large retinal vessels to prevent the aliasing artifact of blood cells from moving faster than the sampling frequency. RESULTS: Branch retinal vein occlusion areas have significantly decreased microvascular blood volume (P = .0009), flow (P = .02), and velocity (P = .016) compared with ipsilateral nonbranch retinal vein occlusion areas in the same eye. Branch retinal vein occlusion areas also have decreased blood volume (P = .001), flow (P = .0042), and velocity (P = .0044) compared with areas of contralateral fellow eyes of branch retinal vein occlusion subjects. Branch retinal vein occlusion areas have significantly decreased blood volume (P = .0012), flow (P = .008), and velocity (P = .02) compared with age-matched normal areas. CONCLUSION: Average retinal blood volume, flow, and velocity in areas of branch retinal vein occlusion are significantly lower than in healthy retinas. The ability to noninvasively measure hemodynamic changes in the retinal capillary bed may be relevant to development of new therapies for retinovascular disease.

Aged↗
PubMed1998

The effect of deep posterior subtenon injection of corticosteroids on intraocular pressure.

PURPOSE: To investigate the effect of posterior subtenon injections of corticosteroids on intraocular pressure in a variety of ocular diseases. METHODS: We retrospectively analyzed 202 consecutive posterior subtenon corticosteroid injections (148 of methylprednisolone acetate, 80 mg, and 54 of triamcinolone acetonide, 40 mg) in 63 eyes of 55 patients (26 male, 29 female; mean age +/- SD, 60.17 +/- 26.55 years). All patients had received topical or systemic corticosteroids before the injection, and no rise in intraocular pressure had been noted. Preinjection and postinjection intraocular pressure measurements were compared by two-tailed paired t test. Statistical analysis was performed separately by patient (first injection of first injected eye), by eye (first injection of each eye), and by all injections. To detect increase in intraocular pressure during follow-up, statistical analysis was performed separately 14 to 90 days, 91 to 150 days, and 151 to 270 days after injection. RESULTS: No statistically significant difference was found between preinjection and postinjection intraocular pressure measurements. A power calculation in the most stringent subanalysis (by patient) proved that there is only a 3.87% chance to statistically miss a clinically significant rise in intraocular pressure from 15 to 21 mm Hg. CONCLUSIONS: Posterior subtenon injection of corticosteroids does not cause an increase in intraocular pressure. All patients in our study had been treated previously with topical or systemic corticosteroids and did not react with an excessive increase in intraocular pressure. This safety of repository corticosteroids may therefore not apply to patients whose status in responding to corticosteroids is not known.

Adolescent↗
PubMed1998

High-dose (2000-microgram) intravitreous ganciclovir in the treatment of cytomegalovirus retinitis.

OBJECTIVE: The authors prospectively studied visual outcome, relapse, complications, and survival of patients with acquired immune deficiency syndrome (AIDS)-related cytomegalovirus (CMV) treated with high-dose intravitreous ganciclovir (2 mg/0.1 ml) injections. The outcomes were compared with those of patients treated with standard doses of intravenous ganciclovir in the same institution. The histopathologic and electrophysiologic effects of high-dose intravitreous ganciclovir injections in rabbits also were studied. DESIGN: A nonrandomized case series. PARTICIPANTS: A total of 42 patients (74 eyes) were treated with intravitreous injections and 18 patients (27 eyes) were treated with intravenous ganciclovir. Five eyes of three New Zealand white rabbits were injected with ganciclovir, and the sixth eye was a control specimen. INTERVENTION: Patients treated with intravitreous injections received twice-weekly doses of 2 mg/0.1 ml ganciclovir for 3 weeks, then weekly injections. Patients treated with intravenous ganciclovir received standard doses. Patients were monitored with regular examinations. Rabbit eyes were given intravitreous injections of 1 mg/0.1 ml of ganciclovir weekly for 4 weeks. MAIN OUTCOME MEASURES: Assessments of vision, retinal inflammation, and survival were made. Electroretinograms were performed on the rabbit eyes, and they were processed for light and electron microscopy. RESULTS: In the intravitreous group, visual acuity (VA) was stable in 64 of 74 eyes, 5 improved, and 5 deteriorated. Sixty-three (85%) of 74 eyes had final VA of 20/20 to 20/40. Relapse occurred in five eyes (7%; median time, 42 weeks). There were three cases of endophthalmitis. Median survival after diagnosis of CMV retinitis was 36 weeks. In the intravenous group, VA was stable in 18 eyes, 0 improved, and 9 deteriorated. Sixteen (59%) of 27 eyes had final VA of 20/20 to 20/40. Relapse occurred in 15 eyes (56%) at a median time of 21 weeks. Median survival was 21 weeks. The rabbit studies showed no evidence of toxicity. CONCLUSION: High-dose intravitreous ganciclovir effectively suppressed CMV retinitis, preserved vision, and prevented relapse without deterioration in survival.

AIDS-Related Opportunistic Infections↗
PubMed1998

Vogt-Koyanagi-Harada syndrome in children compared to adults.

PURPOSE: To study the course and visual outcome of Vogt-Koyanagi-Harada (VKH) syndrome in children. METHODS: The medical records of 97 consecutive patients with VKH syndrome were reviewed. Patients had been seen at King Khaled Eye Specialist Hospital in Riyadh, Saudi Arabia. The records were divided into two groups: those in whom the onset of the disease occurred at the age of 14 years or younger (pediatric group) and those in whom the disease manifested after the age of 14 years (adult group). RESULTS: Eight (61%) of the 13 children required cataract surgery compared to 14(17%) of 84 adult patients. Despite medical and surgical therapy, eight (61%) of the pediatric group had a final visual acuity of 20/200 or worse compared with 22 (26%) of the 84 adult patients (p=0.0103). CONCLUSION: The course of early-onset VKH (before the age of 14 years) appears to be aggressive. The ocular complications are more severe in children than in adults, leading to rapid deterioration in vision. Despite therapy, the final visual outcome of VKH in children is poor.

Adolescent↗
PubMed1998

Lack of reactivation of cytomegalovirus (CMV) retinitis after stopping CMV maintenance therapy in AIDS patients with sustained elevations in CD4 T cells in response to highly active antiretroviral therapy.

The suppression of human immunodeficiency virus (HIV) replication and elevation in CD4 cells observed with protease inhibitor combination regimens known as HAART (highly active antiretroviral therapy) may allow AIDS patients to undergo an immune recovery that allows them to suppress the progression of cytomegalovirus (CMV) retinitis. Eleven AIDS patients receiving HAART with healed CMV retinitis in whom CMV-specific maintenance therapy was discontinued were studied. Median CD4 cell counts were 42 before the initiation of HAART and 183 at discontinuation of anti-CMV therapy. While a median 1.1 log10 drop in plasma HIV-1 RNA was obtained between starting HAART and withdrawal of maintenance therapy for CMV, only 3 of 11 patients maintained plasma HIV RNA below the limits of detection. Reactivation of CMV retinitis after withdrawal of anti-CMV therapy did not occur in any of the patients observed for a median of 156 days (range, 92-558).

AIDS-Related Opportunistic Infections↗
PubMed1998

Visual dysfunction in HIV-positive patients without infectious retinopathy.

Persons with HIV disease are susceptible to various manifestations of retinal damage, such as infectious retinopathies (e.g., cytomegalovirus [CMV] retinitis and toxoplasmosis) and noninfectious complications (microangiopathic infarctions or cotton-wool spots [CWS]); CWS being quite common in AIDS patients. Until recently, little research focused on noninfectious ocular pathology in HIV disease. These disorders may all affect normal functioning of the visual system while funduscopic examination results appear normal. A review of the psychophysical changes, color and contrast sensitivity, peripheral visual function, electrophysiologic and morphologic changes, the relationship of vision loss and neuropsychological changes, postretinal damage, and imaging capabilities cast important new light on quality of life issues and vision function for all HIV/AIDS patients regardless of CD4 count, other measures of wellness, or treatment protocols. Entopic perimetry, a low-cost psychophysical technique screening test, allows sensitive and specific identification of very peripheral areas of visual field loss. The authors recommend its implementation and use by primary care providers, particularly for early detection of retinal damage when funduscopic examination results may appear normal.

Acquired Immunodeficiency Syndrome↗
PubMed1998

Intravitreal and plasma cidofovir concentrations after intravitreal and intravenous administration in AIDS patients with cytomegalovirus retinitis.

This study was undertaken to evaluate the intravitreal and plasma concentrations of cidofovir (HPMPC) after intravitreal and intravenous administration in AIDS patients with cytomegalovirus retinitis. Cohort series; undiluted vitreous and blood were collected from 9 patients at the time of pars plana vitrectomy. Vitreous samples from 9 eyes of 9 patients and plasma samples from 4 patients were assayed with high-performance liquid chromatography to determine cidofovir levels. The only eye that had a detectable vitreous concentration (673.7 ng/ml) was injected with 20 microg 24 hours prior to the surgery. The remaining samples including plasma were below the detection point of the assay (100 ng/ml) and were injected between 5 and 40 days prior to sampling. The intravitreal concentration of cidofovir in humans is consistent with pharmacokinetics data in laboratory animals, and suggests that the long duration of antiviral effect (1-3 months) in clinical trials is due to a prolonged intracellular half-life in retinal tissue.

Acquired Immunodeficiency Syndrome↗
PubMed1998

Modeling human eye aberrations and their compensation for high-resolution retinal imaging.

We introduced a mathematical eye model using Gullstrand's six-surface eye model modified by clinically measured aspherical data to study human eye aberrations and their compensation for high-resolution retinal imaging. Ray tracing was used to characterize aberrations and point spread functions (PSFs) of the eye model. By using the Zernike polynomial decomposition of the calculated pupil function, we quantified the wavefront aberrations. Based on calculated PSFs, we designed optical inverse filters to reduce the aberrations for a large pupil size and improve the resolution. Spherical aberration and oblique astigmatism were found to be in good agreement with published experimental measurements. Spherical aberration and defocus were the most significant aberrations for on-axis imaging, whereas oblique astigmatism and coma combined with spherical aberration and defocus were most significant for off-axis imaging. The best retinal image resolution occurred at 2- to 3-mm pupil diameter. After aberration correction for an 8-mm diameter pupil, the resolutions for on-axis or 9 degrees off-axis imaging points were very close to diffraction-limited resolutions. Over a limited field of view (FOV), retinal image resolution of the eye model can be greatly improved by aberration correction using aspheric and astigmatic lenses. For imaging large FOVs, space-variant compensation techniques will be required for aberration correction.

Astigmatism↗
PubMed1998

Influence of intravitreal injections of HPMPC and related nucleoside analogues on intraocular pressure in guinea pig eyes.

PURPOSE: Cidofovir (HPMPC) is a potent long-acting anticytomegalovirus agent. In humans, its dose-limiting intravitreal toxicity results in the lowering of intraocular pressure (IOP). The purpose of the present study was to determine the effects of HPMPC and various acyclic nucleoside phosphonate (ANP) analogues when administered intravitreally in guinea pig eyes and to establish the structural and functional relation of these compounds in connection with their effects on the ciliary body and retina. METHODS: Ninety-six guinea pig eyes were injected with various doses of HPMPC and ANP analogues. RESULTS: Severe lowering of IOP with structural alterations of the ciliary body was observed when doses were administered that achieved final intravitreal concentrations greater than 25 microg/ml HPMPC, 200 microg/ml cyclic HPMPC (cHPMPC), 25 microg/ml (S)-HPMPA, and 625 microg/ml PMEG. Concentrations of 25 microg/ml HPMPC, 200 microg/ml cHPMPC or less, and all concentrations of (R)-HPMPA, HPMPU, PMEA, PMEC, PMEDAP, (R)-PMPA, and (S)-PMPA did not lower IOP significantly, nor did they cause significant histologic changes. CONCLUSIONS: Of the HPMP series, the cyclic analogue of HPMPC (cHPMPC) and HPMPC are the least toxic of the compounds that show potent anti-human cytomegalovirus activity (HCMV). PMEG, the most potent anti-HCMV compound of the PME series, is toxic at higher doses. Further evaluation of lower doses is needed. Compounds of the PMP series are not toxic, but they show no anti-HCMV activities. The IOP-lowering effect of these compounds appears to be associated with an effect on the ciliary body.

Animals↗
PubMed1998

Effects of topical and subconjunctival cidofovir (HPMPC) in an animal model.

PURPOSE: To characterize the anterior segment effects of cidofovir, using an animal model. METHODS: Cidofovir drops, at concentrations of 0.04%, 0.4% and 4%, were instilled in eyes of guinea pigs once daily for 10 days. Fellow eyes (controls) received normal saline. The corneal epithelium was debrided at day one and then at every other day for 10 days. Subconjunctival injections of 20 microl of 4% cidofovir were given in another group of animals. A micromanometer was used to determine the intraocular pressure (IOP). Eyes were studied histopathologically at the conclusion of the study. RESULTS: There was no significant drop in IOP after 10 days, using the 0.04% concentration of cidofovir drops. Histology revealed mild corneal edema and inflammatory infiltrate; iris, ciliary body and retina were normal. There was a statistically significant drop in IOP in the eyes treated with 0.4% and 4.0% cidofovir eye drops at 10 days (p = 0.005 and p < 0.0001, respectively) compared to baseline. Morphological changes included moderate to severe corneal edema, vascularization and inflammatory infiltration. The iris and ciliary body revealed mild inflammatory changes only at the 4% cidofovir dose. No changes were seen in the retina with any doses. No change in IOP was observed following subconjunctival injections of 4% cidofovir, and histologically, only localized inflammatory changes in the conjunctiva were observed. CONCLUSIONS: The IOP-decreasing effect of cidofovir occurs at doses below those causing intraocular inflammation and is likely due to an effect on the anterior segment. The anterior segment effects of cidofovir in guinea pigs were similar to those in humans. Thus, the guinea pig appears to be a good animal model for studying the effects of cidofovir on the anterior segment structures.

Administration, Topical↗
PubMed1998

Cytomegalovirus iritis.

We describe a case of focal cytomegalovirus iritis in a patient with acquired immunodeficiency syndrome (AIDS) who had CMV retinitis. The autopsy showed histologic evidence of focal iritis in the left eye. This iritis was characterized by infiltration of acute inflammatory cells mixed with cytomegalic cells, which was confirmed by CMV-specific immunohistochemical staining. The case suggested that cytomegalovirus could be a direct causative agent of infectious iritis in AIDS patients.

AIDS-Related Opportunistic Infections↗