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Biomedical subjects

W R Freeman

Publications and source records attributed to W R Freeman.

At least 145 records · Page 8Linked to original sources
PubMed1994

A masked prospective evaluation of outcome parameters for cytomegalovirus-related retinal detachment surgery in patients with acquired immune deficiency syndrome.

PURPOSE: The management of cytomegalovirus (CMV)-related rhegmatogenous retinal detachments in patients with acquired immune deficiency syndrome (AIDS) has been the subject of recent attention and controversy because of the high degree of variability in visual outcome, as well as significant differences in the reported incidence of profound postoperative optic atrophy. This study was designed to evaluate the various parameters affecting postoperative visual outcome, and to quantitate the degree of postoperative optic disc pallor. METHODS: The results of 65 consecutive surgeries for CMV-related retinal detachments in 51 patients with AIDS were prospectively studied. Postoperative vision, survival, optic disc pallor, and retinitis extent were analyzed. Serial photographs of optic discs underwent masked evaluation. RESULTS: Mean postoperative survival was 30 weeks (range, 2-146 weeks). Mean best postoperative visual acuity was 20/66 (range, 20/20-2/200) and mean final postoperative visual acuity was 20/100 (range, 20/25-no light perception). Analysis of visual outcome for eyes with no macular or papillo-macular retinitis showed a best postoperative visual acuity of 20/60 (range, 20/25-2/200) and mean final postoperative visual acuity of 20/80 (range, 20/25-no light perception). Postoperative vision was not affected by the presence of a preoperative macular detachment, with both groups (macula on or off detachments), achieving a best postoperative visual acuity of 20/60 in the absence of macular retinitis. Mild postoperative optic disc pallor was observed in 30% of surgical eyes at the final postoperative visit, and moderate pallor was noted in 13%. The mean degree of optic disc pallor was not different from the degree of optic disc pallor seen in fellow, nonsurgical eyes with CMV retinitis (surgical versus fellow nonsurgical eyes, 29% +/- 23% versus 26% +/- 30%; P = 0.64). CONCLUSION: In this largest reported series of reattachment surgery for CMV-related retinal detachments, patients are experiencing increased postoperative survival, good vision, and relative optic nerve health.

AIDS-Related Opportunistic Infections↗
PubMed1994

CMV-specific immune responses and HLA phenotypes of AIDS patients who develop CMV retinitis. HNRC Group. HIV Neurobehavioral Research Center.

HLA phenotype and immune responses to CMV were studied to determine whether the subset of AIDS patients who developed CMV retinitis were immunogenetically or immunologically predisposed. CMV retinitis develops in approximately 28-35% of AIDS patients and CMV encephalitis develops in 40% of those with retinitis, often leading to death. T-cell proliferation responses to CMV and HIV were assayed prospectively in individuals enrolled in a longitudinal study at the HIV Neurobehavioral Research Center (HNRC) in San Diego. Seventy-three participants, at various stages of disease, have been HLA typed and followed, clinically and immunologically, for up to 5 years. Six HIV infected individuals who eventually developed CMV retinitis, and were assayed prospectively, had a history of low T-cell proliferation to CMV antigens before they were profoundly immunosuppressed. All 10 individuals with CMV retinitis had at least one of three HLA alleles (or combinations): A2B44 (p = 0.02), B51(p = 0.02), or DR7 (p = 0.01) (collective p value = 0.007). Three of the 10 had two or more of these alleles. Of AIDS patients with CD4 counts below 100 and actively at risk for retinitis, 7/15 with A2B44,51, or DR7 have developed retinitis compared to 0/13 without these HLA alleles (relative risk = 23.8). All 4 patients with these alleles who have died, had retinitis. These results suggest that HIV infected individuals with HLA phenotypes A2B44, B51, and DR7 have low T-cell immune responses to CMV and are predisposed to CMV retinitis and encephalitis as immunodeficiency progresses.

AIDS-Related Opportunistic Infections↗
PubMed1994

Long-acting therapy of viral retinitis with (S)-1-(3-hydroxy-2-phosphonylmethoxypropyl)cytosine.

(S)-1-(3-hydroxy-2-phosphonylmethoxypropyl)cytosine (HPMPC), a high-potency antiherpes and anticytomegalovirus (CMV) drug was evaluated in the treatment of experimental retinitis caused by preretinal herpes simplex virus (HSV-1) injection in rabbits. HPMPC (100 micrograms/0.1 mL) was intravitreally injected 10, 15, 21, 30, or 46 days before, concurrently, or 3, 5, or 7 days after viral inoculation. Ganciclovir (200 micrograms/0.1 mL) was intravitreally injected 3, 7, or 10 days before HSV-1 inoculation, concurrent with viral inoculation, or 3, 5, or 7 days after viral inoculation. Eyes pretreated with HPMPC were protected from retinitis for 15-21 days. Ganciclovir did not protect completely even if administered 3 days before inoculation. Early treatment of established retinitis with HPMPC markedly delayed the progression of the infection. However, with ganciclovir there was delayed progression only in rabbits treated 3 days after viral inoculation. HPMPC had a remarkably potent and prolonged (< or = 1 month) antiviral effect in this retinitis model and may prove more useful than ganciclovir in local treatment of CMV retinitis.

Animals↗
PubMed1994

Retinal toxicity of the antimetabolite 5-fluorouridine 5'-monophosphate administered intravitreally using multivesicular liposomes.

BACKGROUND: Liposome-encapsulated 5-fluorouridine-5'-monophosphate (FUMP) has been shown to inhibit proliferative vitreoretinopathy in a rabbit model. Liposome encapsulation extends the intravitreal half-life of this antiproliferative drug by a factor of 28 times. METHODS: The current study investigated the retinal toxicity of intravitreal injections of 10, 50, and 100 micrograms FUMP as free drug or within liposomes in rabbits. Evaluation included ophthalmoscopic examination, electroretinography, and histologic analysis by light and electron microscopy. RESULTS: No electroretinographic evidence for toxicity of FUMP was found. Light and electron microscopy showed only mild transient vacuolization in the outer segment layer, without inflammation. Empty liposomes incurred no toxic effects on the retina. CONCLUSIONS: Our results suggest that liposome-encapsulated FUMP may be non-toxic to the retina at doses that inhibit proliferative retinopathy.

Animals↗
PubMed1993

Risk factors for development of rhegmatogenous retinal detachment in patients with cytomegalovirus retinitis.

We studied 259 patients to determine the time-dependent risk and risk factors for the development of retinal detachment in patients with cytomegalovirus retinitis. The six-month and one-year retinal detachment rates (by eye) were 11% and 24%, respectively. Increasing retinal surface involvement outside of the posterior pole and the presence of retinitis activity were found to be the two covariates that best predicted retinal detachment. Eyes with peripheral involvement greater than 25% had a fivefold risk for detachment, compared to eyes with 10% involvement. If there was retinitis activity and more than 25% peripheral (external to major vascular arcades) involvement, the risk increased to 24-fold. The presence of a fellow eye with retinal detachment was not an independent risk factor. These observations should help in the design of a prophylactic trial intended to prevent retinal detachment and should also help ophthalmologists counsel patients with cytomegalovirus retinitis.

AIDS-Related Opportunistic Infections↗
PubMed1993

Correlation between CD4+ counts and prevalence of cytomegalovirus retinitis and human immunodeficiency virus-related noninfectious retinal vasculopathy in patients with acquired immunodeficiency syndrome.

We prospectively studied 132 patients with acquired immunodeficiency syndrome (AIDS) to determine the cross-sectional prevalence of cytomegalovirus retinitis. All patients had serum CD4+ lymphocyte counts to determine the degree of immune dysfunction. Correlations between CD4+ counts, the presence of cytomegalovirus retinitis or human immunodeficiency virus (HIV)-related noninfectious retinal vasculopathy, and ocular symptoms were made. The study disclosed that 26 of 132 patients with AIDS (20%) had cytomegalovirus retinitis. However, subset analysis according to CD4+ count disclosed that in patients with CD4+ counts of 50 cells/mm3 or less, 26 of 87 (30%) had cytomegalovirus retinitis, whereas in patients with CD4+ counts of 50 cells/mm3 or more, none of 45 was noted to have cytomegalovirus retinitis. Similarly, 46 of 132 patients (35%) were noted to have HIV-related noninfectious retinal vasculopathy, with a trend toward increasing prevalence associated with declining CD4+ count. In patients with CD4+ counts of 50 cells/mm3 or less, 39 of 87 (45%) had HIV-related noninfectious retinal vasculopathy, whereas seven of 45 patients (16%) with CD4+ counts of 50 cells/mm3 or more were noted to have these changes. We confirmed the clinical impression that cytomegalovirus retinitis and HIV-related noninfectious retinal vasculopathy are late manifestations of AIDS, demonstrated an increased risk for patients with low CD4+ counts, and suggested a basis for coherent chemoprophylaxis and screening strategies for cytomegalovirus retinitis.

AIDS-Related Opportunistic Infections↗
PubMed1993

Miliary toxoplasmic retinitis in acquired immunodeficiency syndrome.

A unique pattern of bilateral miliary retinitis due to ocular toxoplasmosis developed in a patient in the late stages of acquired immunodeficiency syndrome. Results of serologic tests for toxoplasmosis remained negative throughout the clinical course of his ocular disease. The retinitis was unresponsive to a brief course of anti-toxoplasmosis therapy. At autopsy, the histopathologic material was consistent with toxoplasmic retinitis and the DNA polymerase chain reaction was positive for toxoplasmosis. Recognition of this pattern of retinitis is important in the appropriate treatment of immunosuppressed patients with retinitis.

AIDS-Related Opportunistic Infections↗
PubMed1993

Combination ganciclovir and foscarnet in the treatment of clinically resistant cytomegalovirus retinitis in patients with acquired immunodeficiency syndrome.

OBJECTIVE: To assess the clinical response and patient tolerance to daily infusions of both ganciclovir sodium and foscarnet sodium for the treatment of clinically resistant cytomegalovirus retinitis in patients with acquired immunodeficiency syndrome. DESIGN AND PATIENTS: Nine patients with clinically resistant cytomegalovirus retinitis who had shown progression of retinitis despite extended intravenous induction single-drug therapy or alternating therapy with induction doses of ganciclovir or foscarnet at 6 weeks were subsequently treated with a combination of ganciclovir and foscarnet. The dosing regimen for induction combination therapy was ganciclovir at 5 mg/kg every 12 hours and foscarnet at 60 mg/kg every 8 hours. Maintenance combination therapy was ganciclovir at 5 mg/kg every 12 to 24 hours and foscarnet at 90 to 120 mg/kg every day. Patients were observed closely for signs of a toxic effect or intolerance to the drug regimen. RESULTS: All patients exhibited a favorable response to combination therapy, with complete healing of retinitis in 12 of 14 eyes and partial healing of retinitis with decreased border activity and a cessation of border advancement in two of 14 eyes. Two of the nine patients stopped receiving combination therapy before completion of the study owing to their dissatisfaction with the time commitment. The regimen was otherwise well tolerated, with no significant medical toxic effects attributable to the drugs requiring cessation of therapy. CONCLUSIONS: Combination anticytomegalovirus therapy should be considered in those patients who have shown a poor clinical response to sustained single-drug induction therapy and alternating drug therapy. As survival time for patients with cytomegalovirus retinitis continues to improve, clinical resistance may become more common. Further work to delineate the optimal dosing and indications for combination therapy will be important.

AIDS-Related Opportunistic Infections↗
PubMed1993

Laser-tissue interaction and artifacts in confocal scanning laser ophthalmoscopy and tomography.

The goal of the present study was to analyze the interaction between incident laser light and retinal tissue in confocal scanning laser ophthalmoscopy and tomography. We examined the change in axial intensity distribution during evaluation of the retinal surface topography in macular and optic nerve head evaluation in normal volunteers and patients with different retinal diseases. Additionally, we examined a model eye with a model cyst and human globes in an eye mounting chamber. We found that confocal scanning laser tomographs record specular reflected light originating from intraocular surfaces as well as light scattering from deeper retinal structures. Concave and convex retinal surfaces and eye movements may influence accurate topographic detection. Knowledge of the exact mechanism of image formation in confocal tomography is of great importance for the understanding of validity of these measurements. Proper identification of observed artifacts and preventive measures will increase the utility, reproducibility, and validity of this technology.

Cysts↗
PubMed1993

A randomized, controlled study of intravenous ganciclovir therapy for cytomegalovirus peripheral retinitis in patients with AIDS. AIDS Clinical Trials Group and Cytomegalovirus Cooperative Study Group.

This prospective, randomized, multicenter, controlled trial was designed to evaluate the efficacy and safety of intravenous ganciclovir for the treatment of peripheral cytomegalovirus (CMV) retinitis in patients with AIDS. Patients were randomly assigned to receive either immediate treatment, intravenous ganciclovir, 5 mg/kg twice daily for 14 days followed by 5 mg/kg once daily for 14 weeks, or deferred treatment. Patients randomized to deferred treatment whose retinitis progressed were offered ganciclovir. Of the 22 patients randomized to deferred treatment who were included in the final analysis, 20 were found to have progressive CMV retinitis compared with 10 of the 13 randomized to immediate treatment. The median time to progression in the deferred treatment group, as determined by a masked fundus photography reading center, was 13.5 days compared with 49.5 days in the immediate treatment group (mean +/- SD, 19.3 +/- 4.1 vs. 66.4 +/- 14.0; P = .001, log rank test). These data indicate that ganciclovir delays the progression of CMV peripheral retinitis in persons with AIDS.

Acquired Immunodeficiency Syndrome↗
PubMed1993

Intravitreal ganciclovir concentration after intravenous administration in AIDS patients with cytomegalovirus retinitis: implications for therapy.

To determine whether therapeutic intravitreal concentrations of ganciclovir are achieved after intravenous administration, vitreous samples were obtained intraoperatively from 23 eyes of 22 AIDS patients with retinal detachments associated with cytomegalovirus (CMV) retinitis. The mean intravitreal ganciclovir concentration of all samples was 0.93 +/- 0.39 microgram/mL (3.6 +/- 1.5 microM). This level is near the published trough serum concentrations obtained with every-12-h intravenous dosing and well below the peak. It is significantly below the concentration of ganciclovir required to achieve 50% of viral plaque formation for many human CMV strains. Only a small decrease in vitreous drug levels was observed as a function of time after last dose. Intravenous administration of ganciclovir results in near-steady-state subtherapeutic intravitreal ganciclovir concentrations for many CMV isolates. This may explain the difficulty of long-term complete suppression of CMV retinitis.

AIDS-Related Opportunistic Infections↗
PubMed1993

Retinal calcifications in cytomegalovirus retinitis.

Cytomegalovirus (CMV) retinitis has been well documented in the literature, both in patients with acquired immune deficiency syndrome (AIDS) and in other immunocompromised hosts. The clinical and histopathologic findings in three patients with AIDS and CMV retinitis are presented. In areas of healed retinitis, focal, yellow-white, plaque-like lesions and small refractile retinal lesions were noted clinically. Histopathologic studies confirmed the plaque-like lesions to be intraretinal calcifications. Detailed clinical pathologic correlation between fundus photographs and histologic material is made and its clinical importance discussed.

AIDS-Related Opportunistic Infections↗
PubMed1993

Evaluation of cytologic specimens obtained during experimental vitreous biopsy.

Vitreous specimens can be useful for diagnosis of intraocular infection, inflammation, and neoplasms. Concern has been raised that obtaining vitreous specimens through a guillotine cutter might result in suboptimal cytologic changes. To determine if aspiration yields better cytologic information than vitrectomy, the authors performed experimental vitreous biopsies on rabbit eyes with vitritis to compare specimens taken by aspiration or vitrectomy with cutting rates of 100, 300, 600 per minute. The specimens were processed by cytospin preparations and stained with Papanicolaou and May-Grünwald-Giemsa stain. There was no difference in the adequacy of the specimens. Cell loss or damage to cell morphologic features when obtaining specimens through aspiration or vitrectomy at different cutting rates could not be differentiated by a blinded cytologic evaluation. A theoretical model of shear stress on cells passing through a guillotine cutter was also developed. The experimental and theoretical data show that vitrectomy with a cutting rate as fast as 600 per minute yields an adequate specimens with a sufficient number of well preserved cells to make definite cytologic interpretations, and that vitreous aspiration is not necessary.

Animals↗
PubMed1993

Visual outcome in acute retinal necrosis.

Acute retinal necrosis (ARN) is generally a progressive retinitis, often complicated by retinal detachment and a poor visual outcome. A series of 12 consecutive patients (13 eyes) with ARN is reported. All patients were examined early, with a limited extent of disease (in 77% of the eyes, less than 25% of retina involved). Patients were treated with high-dose intravenous acyclovir (10 mg/kg every 8 hours) and laser photocoagulation. During a follow-up period of 3 to 21 months, only 1 patient developed a rhegmatogenous retinal detachment resulting in visual loss. No patients developed bilateral disease once intravenous antiviral therapy was begun. Final visual acuity was 20/40 or better in 6 eyes (46%), and 20/400 or better in 12 eyes (92%). Two patients were examined within 6 weeks of extracapsular cataract extraction with intraocular lens implantation. In the majority of the cases, clinical findings were limited to several quadrants of the peripheral retina. Eyes with limited disease, if aggressively treated, have a relatively good visual prognosis.

Acyclovir↗
PubMed1993

An animal model of focal, subacute, viral retinitis.

To study local intravitreal therapies for retinitis due to herpes viruses, an animal model of focal, subacute, relatively nonlethal herpes family retinitis is needed. Herpes simplex virus type 1 (HSV-1) was injected into the subretinal space of 33 Dutch pigmented rabbit eyes. The animals were observed for up to 42 days after the inoculation. All inoculated eyes developed a focal, enlarging area of retinitis in a predictable manner, showing focal enlarging areas of retinal opacification and necrosis with variable retinal hemorrhage. In the inoculated eyes, retinal detachment developed in all animals within 21 days; 33% of the animals developed focal retinitis in the uninoculated eye. Histologic examination showed encephalitis to be present in 11 (73%) of the 15 animals studied after 1 week. This model may be used to evaluate the therapeutic efficacy of new antiviral agents and modalities in the treatment of herpes family viral retinitis. The model is most similar to herpes simplex or zoster retinitis in humans, but also shares some similarities (and differences) with cytomegalovirus (CMV) retinitis in humans.

Acute Disease↗
PubMed1993

Retinal disease associated with AIDS.

In recent years an enormous amount of new information in the area of retinitis and retinal disease in immunosuppressed patients has been acquired. There have been exciting new developments in our understanding of the pathogenesis of retinal disease in AIDS patients as well as important advances in the diagnosis and therapy of infectious retinitis. This article will summarise the recent advances in this area and outline the direction of future research as it applies to the clinical management of patients with retinal manifestations of AIDS. Diagnostic and therapeutic difficulties will be addressed including the appropriate selection of antiviral drugs and other therapeutic modalities in patients with sight-threatening retinitis.

AIDS-Related Opportunistic Infections↗