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W R Freeman

Publications and source records attributed to W R Freeman.

At least 19 recordsLinked to original sources
PubMed2003

Long term visual outcome of patients with cytomegalovirus retinitis treated with highly active antiretroviral therapy.

BACKGROUND: Healed cytomegalovirus (CMV) retinitis in the setting of highly active antiretroviral therapy (HAART) is complicated by inflammatory sequelae and vision loss. AIM: To determine the long term visual outcome of AIDS patients with CMV retinitis who received HAART. METHODS: 90 eyes of 63 consecutive AIDS patients with extramacular CMV retinitis were studied prospectively. RESULTS: Immune recovery status was related to time to onset of epiretinal membrane (p=0.05) and cystoid macular oedema (p=0.06) as well as to the incidence of cataract (p=0.001) and moderate vision loss (p<0.0001). Severe vision loss was associated with retinal detachment (p<0.001). CONCLUSION: AIDS patients with extramacular CMV retinitis lose vision while on HAART. HAART related immune recovery is associated with increased frequencies of epiretinal membrane, cystoid macular oedema, cataract, and retinal detachment with resultant vision loss in AIDS patients with healed CMV retinitis.

AIDS-Related Opportunistic Infections↗
PubMed2002

[Correlation between ICG angiography verified networks in uveal melanomas and rate of tumor regression after brachytherapy].

INTRODUCTION: The post-irradiation regression rate of uveal melanomas is a prognostically significant factor for the development of metastases. Other predictive factors for metastases are histological networks which are imagable with confocal ICG angiography. The purpose of this study was to evaluate a possible connection of networks in the ICGA and tumor regression rates. METHODS: We compared the post-irradiation regression rates (as %) in 20 patients 1 year after brachytherapy with networks identified in pre-treatment indocyanine green angiography (ICGA). The ICG angiography was performed before irradiation, 10 patients were irradiated with Ru-106 and 10 were irradiated with Id-125. RESULTS: The mean preoperative maximum apical height was 5.2 mm [SD: 1.5 mm; Ru106 group: 5.7 mm (SD: 1.0 mm); Id-125 group: 5.0 mm (SD: 1.9 mm)]. In 11 patients (55%) (Ru-106: 5; Id-125: 6) we found networks in the preoperative ICG. The mean regression rate in tumors with networks was 51.3% (SD: 14.7%) and 28.0% (SD: 16.4%) in the group without networks. The difference between both groups was statistically significant (p = 0.003, Mann-Whitney test). No statistically significant difference in the regression rates was found between the two groups of brachytherapy Ru-106 and Id-125 (p = 0.165, Mann-Whitney test). DISCUSSION: Highly proliferative tumors are known to be more sensitive to irradiation. This may be one reason why tumors with a rapid post-irradiation regression are the more aggressive ones with regard to later development of metastases. Histopathological networks are also known to be a strong indication of more aggressive, metastasizing tumors. These networks are also imagable in ICG angiography. Our observation emphasizes a connection between networks in ICG angiography and regression rates of uveal melanomas after brachytherapy.

Adult↗
PubMed2002

[The Munich/San Diego/Iowa City Collaboration (MuSIC). MuSIC Report I: Design , characteristics of the collective and preliminary results].

BACKGROUND: We have previously shown that histologically described microcirculation patterns (MCP) can be visualized with indocyanine green (ICG) angiography. We have designed a prospective study to evaluate the prognostic value of these angiographically imaged MCP in small choroidal melanocytic lesions. In this report we describe the design of the study, characterize the patient collective, and present the first results. PATIENTS AND METHODS: In this prospective nonrandomized observational study, unilateral choroidal melanocytic lesions with 1.5-5.5 mm maximum apical height are observed until growth is determined according to defined criteria. Variables are demographic parameters, subjective symptoms, subretinal fluid, location and dimension of tumor, hemorrhage, color, orange pigment, and MCP determined by ICG angiography: normal, straight, parallel without crosslinking, parallel with crosslinking, arcs without branching, arcs with branching, loop, and network. RESULTS: Seventy patients (22 males, 48 females; age: 33-88 years, median: 64 years) have been included up to now: 19 tumors showed growth so far (time to growth: 51-946 days, median: 127 days). The following parameters were statistically significantly correlated with time to tumor growth: flashes (p = 0.082), orange pigment (p = 0.012), subretinal fluid (p < 0.001), maximum basal tumor diameter (p = 0.001), maximum apical tumor height (p < 0.001), parallel with crosslinking (p < 0.001), arcs with branching (p = 0.006), loop (p < 0.001), and network (p < 0.001). Of these, complex MCP (parallel with crosslinking, arcs with branching, loop and/or network) showed the strongest correlation with time to tumor growth in a Cox regression model. Based on our data, the positive predictive value of imaging complex MCP (for growth within 12 months) is 78% and the negative predictive value is 98%. CONCLUSION: Our patient collective demonstrates comparable prognostic parameters for time to growth as described in the literature. In addition, the ICG angiographic detection of complex MCP is more strongly predictive of the time to growth than other clinically determinable factors. Thus, we recommend this examination for patients with small choroidal melanocytic lesions, if the patient is to be counseled regarding the likely biologic behavior of his tumor.

Adult↗
PubMed2002

Interobserver and intraobserver variability of measurements of uveal melanomas using standardised echography.

AIMS: To report on the intraindividual and interindividual variability of tumour size (height and base diameter) measurements using standardised echography in a masked prospective study. METHODS: 20 consecutive eyes of 20 patients were examined on four different visits by three experienced examiners using standardised echography. As common in standardised echography, tumour height was evaluated with A-scan technique, while transverse and longitudinal base diameter were calculated with B-scan. RESULTS: Tumour height measurements using A-scan were more accurate than base diameter measurements using B-scan. The standard deviation for tumour height over all visits/measurements was 0.18 mm (A-scan), 0.79 mm for transverse, and 0.69 mm for longitudinal base diameters (B-scan). The interclass correlation coefficient (ICC) was much higher for tumour height measurements with A-scan (0.7735 for three examiners on one visit) than for transverse (0.6563) or longitudinal (0.4522) base diameter measurements with B-scan techniques. CONCLUSIONS: A-scan techniques for tumour height measurements provide very reproducible results with little intraindividual and interobserver variability. As B-scan techniques for tumour base evaluation are less accurate they should be used for topographic and morphological examinations.

Adult↗
PubMed2001

Cytomegalovirus (CMV)-specific CD4+ T lymphocyte immune function in long-term survivors of AIDS-related CMV end-organ disease who are receiving potent antiretroviral therapy.

To better understand the relation of cytomegalovirus (CMV)-specific CD4+ T lymphocyte immunity and clinical outcome in AIDS-related CMV end-organ disease, 2 patient groups were prospectively studied: patients recently diagnosed with active CMV end-organ disease and survivors of CMV retinitis who had responded to highly active antiretroviral therapy and had quiescent retinitis when anti-CMV therapy was discontinued. Most patients with active CMV disease had negative CMV-specific CD4+ T lymphocyte responses at diagnosis, as measured by lymphoproliferation (7/7) or cytokine flow cytometry (3/5) assays. In contrast, all 10 subjects with quiescent retinitis and >150 absolute CD4+ T lymphocytes/microL whose anti-CMV therapy was discontinued during 6 months of follow-up had positive CMV-specific immune responses at least once by each assay. However, 6 of these 10 subjects also had negative CMV-specific immune responses > or =1 time. Such patients may be at risk for future CMV disease progression and should be closely monitored.

AIDS-Related Opportunistic Infections↗
PubMed2001

Retinal nerve fiber layer evaluation in human immunodeficiency virus-positive patients.

PURPOSE: To determine the effect of human immunodeficiency virus (HIV) infection on topographic measures of the optic disk and the retinal nerve fiber layer. METHODS: A cross-sectional study at the Acquired Immunodeficiency Syndrome (AIDS) Ocular Research Unit at the University of California, San Diego. Retinal nerve fiber layer thickness at the optic nerve head was evaluated using the Heidelberg Retinal Tomograph, a confocal scanning laser tomograph in 38 HIV-positive and 24 age-matched HIV-negative subjects. RESULTS: HIV-positive patients without CMV retinitis showed significant differences from HIV-negative normal controls in a number of measures of the retinal nerve fiber layer. This indicated a loss of retinal ganglion cells in HIV-positive patients without retinitis. HIV-positive patients with CMV retinitis were worse in most measurements than both HIV-negative controls and HIV-positive patients without CMV. CONCLUSIONS: Significant thinning of the retinal nerve fiber layer occurs in HIV-positive patients without infectious retinopathy, and there are further changes in the optic disk associated with CMV retinitis. Confocal scanning laser tomography may be of use in the diagnosis of early HIV-associated visual function loss.

AIDS-Related Opportunistic Infections↗
PubMed2001

Macular hole surgery in an eye with an optic pit.

PURPOSE: To report an eye with a full-thickness macular hole and an associated optic pit and the noteworthy intraoperative findings. METHODS: Case report. A 56-year-old woman presented with visual acuity LE: 20/100, a full thickness macular hole, and an optic pit. Optical coherence tomography and ophthalmic examination were performed preoperatively and postoperatively. RESULTS: Although usually a macular hole associated with an optic pit tends to be a lamellar and characterized by outer layer defects within preexisting macular detachments or schisis-like cavities, this type of macular hole was not presented in this case. Although the macular hole resembled the idiopathic type on clinical examination as well as on optical coherence tomography, it could only be closed in the third surgical attempt after using silicone oil as a long-standing tamponade. Peeling of an epiretinal membrane or the internal limiting membrane was not possible during any of the three surgeries. CONCLUSION: Our observations suggest that in cases of macular hole in association with optic pit, instillation of silicone oil should be considered in the first surgical procedure, especially if no epiretinal membrane or internal limiting membrane peeling is possible intraoperatively.

Diagnostic Techniques, Ophthalmological↗
PubMed2001

Duration of vitrectomy and postoperative cataract in the vitrectomy for macular hole study.

PURPOSE: To report the association between duration of vitrectomy, as well as other risk factors, and the progression of nuclear sclerosis and posterior subcapsular cataract in the Vitrectomy for Macular Hole Study. DESIGN: A cohort study nested within a randomized controlled clinical trial. METHODS: Using a system similar to the Lens Opacities Classification System II, nuclear sclerosis (NS) and posterior subcapsular cataract (PSC) were scored in the vitrectomy and fellow eye of 74 patients at baseline and at 6, 12, and 24 months postoperatively. Age, baseline blood pressure and refractive power, and duration of surgery were evaluated as risk factors for NS or PSC progression and cataract extraction. RESULTS: The incidence of NS progression in the surgical group of vitrectomy eyes was 81% at 6 months, 98% at 1 year, and 100% at 2 years of follow-up. In contrast, NS progression in the control group of fellow eyes was only 18% at 6 months, 20% at 1 year, and 8% at 2 years. The incidence of PSC progression in the surgical group remained at approximately 11% throughout follow-up, which was not significantly higher than the 3% to 5% incidence in the control group. Vitrectomy was significantly related to progression of NS cataract (P <.001) and cataract extraction (P <.01). No statistically significant differences were found for NS scores, PSC scores, or progression rates between eyes that had less than median surgical duration (60 min.) or more than the median surgical duration. Additionally, no significant differences were found when eyes that experienced 45 minutes or less surgical duration were compared with eyes that endured more than 75 minutes surgical duration. Age, blood pressure, and refractive power were not found to be predictors for NS and PSC progression. CONCLUSIONS: Although vitrectomy is a risk factor for NS progression, the duration of vitrectomy does not increase the risk.

Age Factors↗
PubMed2001

Retinal detachment.

RD is a serious and well-known complication after cataract surgery, developing in 1% to 3% of all patients undergoing cataract extraction. High myopia, disruption of the posterior capsule intraoperatively or postoperatively by Nd: YAG laser, and vitreous loss increases the risk for RD. Retinal evaluation with detailed indirect ophthalmoscopy with scleral indentation and prophylactic treatment to all lesions that contribute to retinal tear and RD is strongly advocated before cataract surgery and Nd: YAG laser capsulotomy. Intraoperative vitreous loss should be managed meticulously, and these patients should be examined more frequently in the postoperative period. During phacoemulsification, no attempts should be made to retrieve the dislocated nuclear fragments without proper vitrectomy. It is best advised that a vitreoretinal surgeon handles the complication. Early recognition and prompt treatment following the detachment can result in good visual recovery.

Cataract Extraction↗
PubMed2001

Imaging the microcirculation of untreated and treated human choroidal melanomas.

INTRODUCTION: Histologically demonstrable microcirculation patterns (microcirculation pattern) of human choroidal melanomas have prognostic significance for the patient. We report on our experience in imaging these microcirculation pattern in vivo using simultaneous confocal Fluorescein (FA)- and Indocyaninegreen (ICG) angiography before and after brachytherapy. PATIENTS AND METHODS: The simultaneously procured confocal FA- and ICG angiograms of 50 patients with untreated choroidal melanomas were studied for the visibility of microcirculation pattern. Patients were also followed with simultaneous FA/ICG after brachytherapy. RESULTS: Confocal FA disclosed signs of tumor vascularization in 12 (24%) of the 50 examined patients but microcirculation pattern only in 3 patients (6%). In contrast, simultaneously obtained confocal ICG disclosed microcirculation pattern in 47 patients (94%). In 10 (77%) of the 13 patients the tumor microcirculation changed considerably after brachytherapy: Distortion, thickening, thinning, as well as complete obliteration of vessels could be observed. CONCLUSION: Histologically demonstrated microcirculation pattern can be imaged in vivo. This offers the possibility to assess the likely biologic behavior of the individual tumor without the need for obtaining a cytologic or histologic specimen via enucleation or fine-needle biopsy. Confocal ICG angiogiography images microcirculation pattern better than FA which can be explained by the different absorption-, fluorescence- and exudation-characteristics ICG. Follow-up with confocal ICG of choroidal melanomas after brachytherapy shows different features and allows for visualization of the microcirculation reaction to the treatment which might be a useful tool for studying the effects of future anti-angiogenesis based tumor therapies.

Adult↗
PubMed2001

Evaluation of intraocular pharmacokinetics and toxicity of prinomastat (AG3340) in the rabbit.

To determine the ocular pharmacokinetics, physiological and histological effects of prinomastat (a matrix metalloprotease inhibitor), a total of seventy-seven eyes of New Zealand White rabbits received intravitreous and subtenon injections of prinomastat or of acidified water vehicle as control, Doses of 0.5 mg in 0.05 mL of prinomastat or acidified water were used for intravitreal injection. For the subtenon injections, doses of 5 mg prinomastat in 0.5 mL of acidified water were administered in the superotemporal quadrant. Intraocular pharmacokinetics were determined by analyzing vitreous samples at different postinjection time points using Liquid Chromatography-Mass Spectroscopy/Mass Spectroscopy (LC-MS/MS). The toxicity was evaluated by biomicroscopy, electroretinography (ERG), pneumatonometry, and histology. No toxicity was found with either administration method. At day 14 after intravitreal injection, levels of prinomastat in the vitreous and choroid were 1.4 ng/mg and 7.8 ng/mg, respectively. The retinal levels of prinomastat were 22 ng/mg at 24 hr and dropped below 1 ng/mg at 48 hr. Prinomastat remained well above minimum effective concentration in the choroid for at least four weeks after a single intravitreal injection, suggesting that local intravitreal injection may have potential in treating choroidal neovascularization.

Angiogenesis Inhibitors↗
PubMed2001

Immune recovery vitritis and uveitis in AIDS: clinical predictors, sequelae, and treatment outcomes.

PURPOSE: To determine 1) clinical predictors of an inflammatory syndrome associated with cytomegalovirus (CMV) retinitis (immune recovery vitritis or uveitis [IRV or IRU]); 2) clinical sequelae of IRV; and 3) the effect of corticosteroid treatment on visual acuity. METHODS: A cohort study from the AIDS Ocular Research Unit of the University of California, San Diego, and a case series from the Cleveland Clinic consisted of patients who had acquired immunodeficiency syndrome and inactive CMV retinitis who responded to highly active antiretroviral therapy (HAART) with CD4 T-lymphocyte levels >60 cells/mm3. The cohort was followed for a median of 13.5 months following increase in CD4 count. The authors studied the occurrence of IRV, defined as symptomatic (vision decrease and/or floaters) vitritis of 1+ or greater severity associated with inactive CMV retinitis. Macular edema or epiretinal membrane formation was determined by clinical examination and fluorescein angiography. Five eyes were treated with sub-Tenon corticosteroid injections. RESULTS: In the cohort study, 19 (63%) of 30 HAART responders developed IRV (26 eyes). The clinical spectrum of inflammation included vitritis, papillitis, macular edema, and epiretinal membranes. Eyes with CMV surface area >30% of the retina were at the highest risk (relative risk = 4.5) of developing IRV (P = 0.03). During follow-up, inflammation persisted without treatment for a median of 20 weeks and 14 patients (16 eyes) developed macular changes. Treatment resulted in vision improvement without reactivation of retinitis. Histology and immunohistochemistry of associated epiretinal membranes showed evidence of chronic inflammation with a predominant T-lymphocyte cell population. In the case series, 3 (38%) of 8 HAART responders developed IRV (4 eyes). All four eyes were treated and resulted in visual acuity improvement of one line. CONCLUSIONS: Symptomatic IRV or IRU develops in a significant number of patients with CMV retinitis following successful HAART. Eyes with CMV surface area >30% of the retina are at the greatest risk. Eyes with IRV respond favorably to antiinflammatory therapy without reactivation of retinitis. Immune recovery vitritis may be the result of an immunologic reaction to latent CMV antigens in the eye in which T-lymphocytes play a role.

AIDS-Related Opportunistic Infections↗
PubMed2001

Highly active antiretroviral therapy-associated regression of cytomegalovirus retinitis: long-Term results in a small case series.

PURPOSE: To report the stability of acquired immunodeficiency syndrome (AIDS)-associated cytomegalovirus (CMV) retinitis lesions that have undergone regression in the absence of specific anti-CMV medications owing to highly active antiretroviral therapy (HAART)-generated immune recovery. METHODS: The initial examination revealed HAART-associated regression of CMV retinitis lesions in eight subjects at two institutions. Patients were monitored for recurrences of CMV activity. CD4+ T-lymphocyte counts and human immunodeficiency virus (HIV) loads were measured. RESULTS: All patients had positive initial responses to HAART with an average HIV load decrease of 2.26 log units (range 0.3-5.57). Mean CD4+ T-lymphocyte count at baseline was 45.6 (range 4-107) and increased by an average of 132.5 (range 7-266) within the first 2 to 4 months of HAART. Patients were observed for an average of 15.5 months (range 11-20 months). Six subjects had a vigorous and sustained response to therapy, achieving an average HIV load of 9,400 copies/mL (3.32 log10 decrease) and CD4+ T-lymphocyte count of 158.2 cells/microL. These patients had no CMV retinitis progression. By contrast, two others who attained an average log10 decrease of only 0.48 had modest and short-lived increases in the CD4+ T-lymphocyte count. These patients experienced reactivation of CMV retinitis after 5 and 7 months, respectively. CONCLUSIONS: Regressed CMV retinitis may remain healed for long periods. However, failure of HAART to induce substantial decreases in HIV load may predict poor or unsustainable rises in the CD4+ T-lymphocyte count and presage recurrence of CMV retinitis. Vigilance in ophthalmic examinations is especially mandatory in these subjects.

AIDS-Related Opportunistic Infections↗
PubMed2000

CMV retinitis recurs after stopping treatment in virological and immunological failures of potent antiretroviral therapy.

OBJECTIVES: To determine predictors of clinical relapse of cytomegalovirus (CMV) end-organ disease in a cohort of 17 HIV-infected patients with healed and treated CMV retinitis (CMVR) who responded to HAART with an increase in CD4 cell counts to above 70 cells/mm3 and discontinued CMV maintenance therapy (MT). DESIGN: Seventeen patients were monitored for reactivation of retinitis. The CD4 cell counts, HIV RNA and peripheral blood mononuclear cell (PBMC) lymphoproliferative assays to CMV at 3 month intervals were compared between patients with and without reactivation of CMVR. Positive lymphoproliferative responses were defined as a stimulation index of 3 or greater. RESULTS: Five out of 17 (29%) patients experienced a recurrence of CMVR a mean of 14.5 months after stopping CMV MT and between 8 days and 10 months after CD4 cell counts fell below 50 cells/mm3. Median CD4 cell counts and plasma HIV RNA at reactivation were 37 cells/mm3 and 5.3 log10 copies/ml. Three patients recurred at a previously active site of the retina, one had contralateral CMVR, and one a recurrence of retinitis and pancreatitis simultaneously. Mean lymphoproliferative responses to CMV were 2.4 in patients with reactivation versus 21.0 stimulation index (SI) in patients without reactivation (P= 0.01). A model incorporating four variables (CD4 cell counts and HIV RNA at maintenance discontinuation, highest CD4 cell count, nadir HIV RNA and median lymphoproliferative responses) identified correctly 88% of patients with and without reactivation. CONCLUSION: CMV disease recurs after virological and immunological failure of HAART if CD4 cell counts drop below 50. In this situation, anti-CMV agents should be resumed before clinical reactivation ensues, because of the risk of contralateral retinal involvement and systemic disease.

AIDS-Related Opportunistic Infections↗
PubMed2000

Scanning laser entoptic perimetry for the screening of macular and peripheral retinal disease.

OBJECTIVE: To determine the effectiveness of scanning laser entoptic perimetry as a noninvasive platform for screening for retinal damage in visually asymptomatic patients within the central 120 degrees (diameter) of vision. DESIGN: A masked study comparing entoptic perimetry with fundus photographs. SETTING: The Shiley Eye Center and the AIDS Ocular Research Unit at the University of California, San Diego. PATIENTS: Fifty-eight patients recruited during ophthalmologic visits for treatment or follow-up of ocular disease. MEASUREMENTS: For each testing session, we compared the presence of a disturbance in the entoptic stimulus with the presence of retinal disease within the central 120 degrees of vision, centered on the fovea. RESULTS: Scanning laser entoptic perimetry has a sensitivity and specificity of more than 90%, a positive predictive value of 100%, and a negative predictive value of 89% for screening retinal lesions within the central 120 degrees diameter of vision. CONCLUSION: Scanning laser entoptic perimetry may be an effective and inexpensive screening test for diagnosing retinal disease in hospitals and community clinics. Arch Ophthalmol. 2000;118:1205-1210

False Positive Reactions↗