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Biomedical subjects

William R Freeman

Publications and source records attributed to William R Freeman.

At least 19 recordsLinked to original sources
PubMed2006

In vivo histology of cotton-wool spots using high-resolution optical coherence tomography.

PURPOSE: To provide optical characteristics of cotton-wool spots (CWS) on optical coherence tomography (OCT) and scan the retina after CWS have ophthalmoscopically disappeared. DESIGN: Observational case reports. METHODS: We studied four eyes of four patients with retinopathy due to human immunodeficiency virus (HIV) and hypertension. The StratusOCT Model 3000 in single-line mode was used for imaging of acute and resolved CWS and adjacent normal retina. The fundus photography served as a template for OCT scanning in localization of CWS. Retinal tissue reflectivity images were compared. RESULTS: There were differences in reflectivity of normal retina, the retina in the area of active CWS, and the retina in the same area after CWS has resolved. Most striking was that the OCT documented a persistent focal area of hyper-reflectivity in the area of the resolved CWS, indicative of retinal gliosis that could be imaged. CONCLUSIONS: CWS show a hyper-reflective pattern on OCT that persists even after they become ophthalmoscopically invisible.

Diagnostic Techniques, Ophthalmological↗
PubMed2006

Nonprogressive extrafoveal retinal hole after foveal epiretinal membrane removal.

PURPOSE: To report an extrafoveal posterior retinal hole after surgical removal of foveal epiretinal membrane. DESIGN: Observational case reports. METHODS: We describe two patients who underwent vitrectomy surgery with an epiretinal membrane removal. Five months after vision improving surgery, a small retinal hole outside the macular area developed. RESULTS: Fundus photography and optical coherence tomography showed a full-thickness retinal hole with a surrounding cuff of subretinal fluid smaller than described in stage III or IV macular holes. The hole has been stable in shape and dimension, has not progressed to retinal detachment, and is not associated with an epiretinal membrane; the fluid is not impinging on the macular area. CONCLUSIONS: Asymptomatic full-thickness extrafoveal retinal holes, which do not progress to neurosensory detachment, can develop after epiretinal membrane peeling. These appear stable and have substantially smaller cuffs of subretinal fluid than typical macular holes.

Aged↗
PubMed2006

Long-term study of intraocular pressure changes in patients with human immunodeficiency virus treated with highly active antiretroviral therapy.

PURPOSE: To characterize a longitudinal relationship between highly active antiretroviral therapy immune recovery as defined by an increase in CD4 cell counts and any associated changes in intraocular pressure (IOP) in both patients with and patients without a history of cytomegalovirus (CMV) retinitis and to determine if human immunodeficiency (HIV)-induced reduction in IOP is reversible. DESIGN: Retrospective analysis of patient data collected from 1997 through 2004. PARTICIPANTS: Cohort of patients from one eye center, including patients from the Longitudinal Study of Ocular Complications of Acquired Immunodeficiency Syndrome. METHODS: Linear regression analyses were conducted within the CMV and non-CMV groups to determine the change in IOP per 100-unit change in CD4 count. Average changes in IOP per change in CD4 count were compared between the CMV and the non-CMV groups using a Wilcoxon rank-sum test. Linear regression analyses were conducted within the CMV and non-CMV groups to determine the linear relationship between the 12-month change in IOP per 12-month 100-unit change in CD4 count. MAIN OUTCOME MEASURE: Intraocular pressure in relation to changes in CD4 cell counts. RESULTS: Compared with the non-CMV group, the median IOP change per change in CD4 count was not statistically different from the CMV group (0.9 vs. 1.7 mmHg/100 CD4 cells, respectively; P = 0.20). Analysis of the linear relationship between the 12-month change in IOP and the 12-month change in CD4 count within both the CMV and non-CMV groups showed a strong linear relationship: 67% of the variability in a 12-month IOP change for the CMV group (P<0.0001) and 36% of the variability in a 12-month IOP change for the non-CMV group (P<0.001). CONCLUSIONS: Reduction in T-lymphocyte count in HIV infection is accompanied by a decrease in IOP in both CMV-infected and non-CMV-infected eyes, and immune recovery is associated with an increase in IOP.

Adult↗
PubMed2006

Risk of immune recovery uveitis in patients with AIDS and cytomegalovirus retinitis.

OBJECTIVE: To evaluate the prevalence of and risk factors for immune recovery uveitis (IRU) in eyes of patients with AIDS and cytomegalovirus (CMV) retinitis. DESIGN: Enrollment data from a 19-clinical center cohort study. PARTICIPANTS: Three hundred seventy-four patients with AIDS and CMV retinitis affecting 539 eyes. METHODS: Patients with AIDS were enrolled at 19 United States AIDS ophthalmology clinics. Data were collected by interview, review of medical records, ophthalmic examination, and phlebotomy. MAIN OUTCOME MEASURE: Immune recovery uveitis. RESULTS: Thirty-six patients (9.6%) were diagnosed with IRU involving 50 eyes. The CD4+ T-cell count of 31 of these had risen by > or =50 cells per microliter above nadir to a level > or = 100 cells per microliter (immune recovery), making up 17.6% of the patients known to have immune recovery after diagnosis of CMV retinitis (95% confidence interval, 12.3%-24.1%). No patients with IRU were observed to have active retinitis or detectable CMV DNA in peripheral blood (P<0.001 and P<0.001 with respect to patients without IRU). Other factors associated with IRU were > or =25% retinal area (odds ratio [OR], 2.72; P = 0.014) or posterior pole involvement with CMV retinitis (odds ratio, 0.43; P = 0.039), treatment with intravitreous injection of cidofovir (OR, 10.6 with respect to eyes never exposed to intravitreous or IV cidofovir; P<0.001), and male gender (OR, 0.26; P = 0.012). More eyes with IRU had visual acuity (VA) of 20/50 or worse (38.0% vs. 26.3%, P = 0.077) relative to eyes without IRU, but the proportions with VA of 20/200 or worse were similar (14.0% vs. 13.8%, P = 0.96). Eyes with IRU more commonly had cystoid macular edema (CME) (45.5% vs. 3.7%, P<0.001) and epiretinal membrane (48.9% vs. 13.3%, P<0.001) than eyes without IRU. CONCLUSIONS: Among eyes of patients with immune recovery, the prevalence of IRU is substantial. Eyes with IRU have a high risk of additional morbidity over and above that seen with CMV retinitis, with several-fold higher risk of CME and epiretinal membrane. Large CMV lesions and use of intravitreous cidofovir are risk factors for IRU.

AIDS-Related Opportunistic Infections↗
PubMed2006

Therapy with ribozyme to the proliferating cell nuclear antigen-ribozyme and 5-fluorouracil of experimental choroidal neovascularization in rats.

PURPOSE: The aim of this study was to evaluate the efficacy of hammerhead ribozyme to the proliferating cell nuclear antigen (PCNA-Rz) and 5-fluorouracil (5-FU) in experimental choroidal neovascularization (CNV) model in rats. METHODS: Laser was used to induce CNV in each eye of 44 rats. For angiography studies, injections of either a mixture of PCNA-Rz 10 microg/microL and 5-FU 1.5 microg/microL, versus the same dose of either drug alone versus a control injection of Hanks' Balanced Salt Solution (HBSS) were performed. We also studied this regimen to evaluate scar size and volume. RESULTS: There was significantly less angiographic leakage for the treated eyes compared to the controls by 3.53 grading points (P = 0.0005); CNV leakage was reduced in the combination group compared to 5-FU alone by 1.75 grading units (P = 0.04) and compared to PCNARz by 2.22 grading units (P = 0.07). The scar size and volume were smaller (diameter 354.6 +/- 174.2 microm vs 477.3 +/- 157.0 microm), (thickness 52.7 +/- 43.0 microm versus 79.6 +/- 46.2 microm) with a reduction in scar volume of 44.8%. CONCLUSIONS: Subretinal injection of PCNA-Rz and 5-FU mixture is more effective as treatment of laser-induced CNV, than either drug alone. The majority of the antiangiogenic effect is a result of 5-FU activity with a contribution by the PCNA ribozyme.

Animals↗
PubMed2006

The effect of recombinant human hyaluronidase on dexamethasone penetration into the posterior segment of the eye after sub-Tenon's injection.

PURPOSE: The aim of this study was to investigate the extent if recombinant human hyaluronidase (rhuPH20) can enhance trans-scleral penetration of sub-Tenon's dexamethasone (DM) into the posterior segment of the eye. METHODS: rhuPH20 was purified from conditioned media through a series of ion exchange, hydrophobic interaction, aminophenylboronate, and hydroxyapatite chromatography to greater than 90% purity based upon specific activity. Only the right eye of each rabbit was injected. The first group (n = 16) received an injection of DM and rhuPH20, whereas the second group (n = 16) received DM only. The eyes were enucleated 1, 2, 3, and 6 h after the injection, and the choroid, retina, vitreous, aqueous, and serum were harvested. DM concentration was assessed by mass spectrometry. Histology (n = 2) and immunohistochemistry (n = 2) was performed to detect toxicity and the presence of the rHuPH20, respectively. RESULTS: We observed no histopathologic damage to ocular tissues after sub-Tenon's injection. This enzyme significantly increased DM level in the choroid and the retina 3 h after administration. The rise in levels was transient returning to normal levels by 6 h. CONCLUSIONS: Sub-Tenon's coinjection of rHuPH20 with DM resulted in a general increase in DM levels in ocular tissues and the serum, with significant increase in the choroid and the retina, 3 h after administration.

Animals↗
PubMed2006

Intraocular viral and immune pathogenesis of immune recovery uveitis in patients with healed cytomegalovirus retinitis.

PURPOSE: To investigate immune and viral contributions to the pathogenesis of immune recovery uveitis (IRU), which presents as vitritis, macular edema, or formation of epiretinal membranes, and develops in patients with acquired immunodeficiency syndrome (AIDS) who experienced cytomegalovirus (CMV) retinitis before antiretroviral treatment (ART) induced immune reconstitution. METHODS: Aqueous and vitreous fluids from patients with IRU, active CMV retinitis, and control human immunodeficiency virus (HIV)-negative, noninflamed eyes were compared for presence of cytokines IL-6, IL12, interferon gamma using enzyme-linked immunosorbent assay techniques, and CMV DNA (by polymerase chain reaction). RESULTS: IRU eyes (11 patients, 18 samples) had the highest levels of IL-12 (median 48 pg/mL), moderate levels of IL-6 (median 146 pg/mL), and low but significant interferon gamma (median 15 pg/mL), compared to controls (P < 0.01). All uveitis eyes tested (9/9) were CMV DNA negative. In contrast, active CMV retinitis eyes were CMV DNA positive, had higher levels of IL-6 (median 349 pg/mL) (25 patients, 41 samples) than both control (P = 0.0001) and uveitis eyes (P = 0.048), similar levels of interferon gamma (median 27 pg/mL) to uveitis eyes, but less IL-12 (median 0 pg/mL) than uveitis eyes. CONCLUSIONS: Inflammatory IRU can be differentiated from active CMV retinitis by the presence of IL-12, less IL-6, and absence of detectable CMV replication.

AIDS-Related Opportunistic Infections↗
PubMed2006

Effect of a novel octapeptide urokinase fragment, A6, on experimental choroidal neovascularization in the monkey.

PURPOSE: To evaluate the inhibitory effects of a urokinase-derived octapeptide, A 6, on laser-induced choroidal neovascularization (CNV) in monkeys. METHODS: Twenty female cynomolgus monkeys were randomly grouped into weekly or monthly A 6 treatment groups, each consisting of 10 animals. CNV was induced in both eyes by perimacular laser treatment. In each right eye, a single 22.25-mg A 6 dose (monthly group) or 4 22.25-mg A 6 doses each week (weekly group) were given by intravitreal injections. Each left eye received phosphate buffer on the same schedule. Monkeys were observed for 4 weeks by ophthalmic examinations, color photography, and fluorescein angiography. RESULTS: Weekly treated eyes had a 35% reduction of CNV compared with controls (P = 0.23). In contrast, monthly treated eye had a 71% reduction of CNV compared with controls (P = 0.0009). There was no evidence of toxicity at both clinical and pathologic examinations. CONCLUSIONS: Intravitreal A 6 injections effectively inhibited CNV in cynomolgus monkeys without evidence of toxicity. The overall reduction in CNV was greater for monthly treated eyes than for weekly treated eyes. This study suggests that A 6 has promise as a local antiangiogenic treatment of CNV. Further work is indicated to evaluate the potential role of A 6 in therapy for human CNV associated with age-related macular degeneration.

Angiogenesis Inhibitors↗
PubMed2006

Intravitreal toxicity of the kenalog vehicle (benzyl alcohol) in rabbits.

PURPOSE: To test the toxicity of intravitreal injections of benzyl alcohol. METHODS: Nine New Zealand rabbits were injected with either a control or a test article at elevating concentrations. The test article was benzyl alcohol calculated to give final injected concentrations of 0.0073%, 0.022%, 0.073%, 0.222%, and 0.733% benzyl alcohol. The 0.022% concentration corresponds to the concentration of benzyl alcohol in human eyes when 0.1 mL of commercial Kenalog (Bristol-Myers Squibb, Princeton, NJ) is used. Baseline examination of the rabbits was performed along with postinjection examinations on days 1, 3, 7, and 14. The eyes were enucleated and examined by light and electron microscopic examinations. RESULTS: Eyes injected with benzyl alcohol concentrations of 0.073%, 0.222%, and 0.733% displayed changes in the outer retina including loss of, and shortening of, outer segments and photoreceptors. CONCLUSIONS: Benzyl alcohol at concentrations modestly higher than what is present in commercial Kenalog is toxic to the rabbit eye. This has been shown in other organ systems. If commercial preserved Kenalog is to be used clinically, decanting the supernatant or using other means to remove the benzyl alcohol may be considered, especially if a volume of >0.1 mL of solution is used. We hypothesize that the noninfectious inflammation seen clinically after Kenalog injection is due to the presence of a toxic preservative at unsafe concentrations.

Animals↗
PubMed2006

Evaluation of the toxicity of subretinal triamcinolone acetonide in the rabbit.

PURPOSE: Subretinal triamcinolone acetonide (TCA) might be a useful adjuvant in the treatment of subretinal neovascularization. The purpose of this study was to test the toxicity of subretinal TCA in the rabbit eye. METHODS: Sixteen New Zealand rabbits were vitrectomized and injected with either decanted TCA solution or vehicle. The concentration of injected TCA was 2 mg, and the delivered volume was 10 microL. Rabbits were examined on days 1, 3, and 7 and then once a week up to 3 months after surgery. Optical coherence tomography was performed at months 1, 2, and 3. After the last examination, which included electroretinography, the rabbits were killed, and the eyes were enucleated for histopathologic analysis. RESULTS: Subretinal TCA appeared as a white circumscribed deposit. As the drug disappeared, areas of hyperpigmentation were seen adjacent to the drug deposit. Electroretinography tracings were normal, indicating no widespread toxic effect. Histologic analysis revealed areas of absence and/or hyperpigmentation of the retinal pigment epithelium and damage to photoreceptors and the outer nuclear layer of the retina. CONCLUSION: Subretinal injection of TCA crystals can be toxic to the outer retina and retinal pigment epithelium. Whether the potential beneficial effect of such a high-dose steroid in limiting subretinal inflammation, angiogenesis, and proliferation outweighs toxicity can only be determined from a clinical trial.

Animals↗
PubMed2006

Assessment of retinal function in patients with HIV without infectious retinitis by multifocal electroretinogram and automated perimetry.

PURPOSE: To determine if multifocal electroretinogram (mfERG) testing shows abnormalities that correspond to perimetric defects in HIV positive patients without infectious retinitis. METHODS: We studied three groups of patients: HIV negative controls, HIV high CD4 nadir patients (lowest CD4 T cell count is over 100) and low CD4 nadir patients (below 100 for over 6 months). Twenty-six HIV positive eyes and 16 HIV negative control eyes were studied by mfERG. A subset of 10 eyes also underwent computerized perimetry for comparison. We analyzed mfERG by hexagons as well as by quadrants and rings. RESULTS: Of 103 hexagon locations there was no significant difference in the amplitudes P1 and N1 (nV/degree) between the three studied groups (p>0.05), similarly, the latencies were not different (p>0.05). All eyes with significant visual field defects at the 0.01 and 0.005 level (Humphrey pattern deviation; 24-2) were compared to mfERG amplitudes and latencies at those locations-there were no corresponding defects in mfERG data (p>0.2). CONCLUSION: In the era of HAART there are still demonstrable visual field defects and other evidence of damage to the retinal nerve fiber layer in HIV patients. Our mfERG studies show that the damage appears to affect the inner retina, the outer retina is spared. Further studies of inner retinal structure and function are indicated to elucidate this process.

Adult↗
PubMed2005

Results of silicone oil removal in patients with cytomegalovirus retinitis related retinal detachments.

PURPOSE: To evaluate the percentage and risk indicators leading to retinal redetachment in HIV (human immunodeficiency virus) patients with CMV (cytomegalovirus) retinitis related retinal detachments that were repaired with silicone oil, and then subsequently underwent oil removal. DESIGN: Retrospective, noncomparative interventional case series. METHODS: The study cohort consisted of a series of 15 eyes in 14 patients with HIV and CMV retinitis with a retinal detachment (RD) repaired with silicone oil at a single center and followed from the time of the CMV retinitis diagnosis through the time of silicone oil removal. Patient- and eye-specific data regarding demographic and clinical characteristics were collected retrospectively and statistical analyses were performed to compare differences between the eyes that had retinal detachments versus the eyes that remained attached following removal of silicone oil. RESULTS: Eight eyes (53%) redetached after a median of 4.0 months following oil removal. Cataract surgery performed at the time of oil removal was a statistically significant risk factor for redetachment (P = .01). There was a trend for lower CD4 levels to be associated with a higher risk of retinal redetachment. The use of a scleral buckle at the time of surgery (initial RD repair or at the time of oil removal) did not reduce the risk of redetachment. CONCLUSIONS: Approximately half of the eyes with CMV related retinal detachment may safely undergo oil removal. The risk factor for redetachment was simultaneous cataract extraction at the time of silicone oil removal. There was also a trend for lower CD4 levels to be associated with a higher risk of retinal redetachment.

AIDS-Related Opportunistic Infections↗
PubMed2005

Objective analysis of retinal damage in HIV-positive patients in the HAART era using OCT.

PURPOSE: To assess retinal nerve fiber layer (RNFL) thickness in patients with human immunodeficiency virus (HIV) disease without cytomegalovirus retinitis (CMV). DESIGN: A case-control study. METHODS: The study included 113 eyes of 65 patients in one center. Thickness of RNFL along a 3.4-mm-diameter circle centered on the optic nerve head was evaluated using third-generation optical coherence tomography. Patients in group A (39 eyes of 22 patients) were human immunodeficiency virus-negative control subjects. Group B (36 eyes of 18 patients) was composed of HIV patients with no history of CMV retinitis and CD4 counts consistently above 100. Group C (38 eyes of 25 patients) comprised HIV patients with no history of CMV retinitis but a history of CD4 count less than 100 at some point lasting for at least 6 months. RESULTS: The average RNFL thicknesses in groups A, B, and C were 103.33 +/- 8.50 microm, 103.30 +/- 9.28 microm, and 90.10 +/- 12.50 microm, respectively. Group C had significantly thinner overall RNFL than either of the groups A and B (Tukey-Kramer). This difference was most prominent in temporal, superior, and inferior retinal areas. No difference was in nasal retinal area, nor between groups A and B in any of the areas. CONCLUSIONS: Significant RNFL thinning occurs in HIV patients without CMV retinitis and with low CD4 counts compared with the same subgroup of patients with CD4 count increased to above 100 and HIV-negative control subjects. Third-generation OCT may be useful in diagnosis of early subclinical HIV-associated visual functional loss.

Adult↗
PubMed2005

Effect of subthreshold infrared laser treatment for drusen regression on macular autofluorescence in patients with age-related macular degeneration.

BACKGROUND: Subthreshold laser therapy has been shown to cause drusen reduction. Using this method, visible laser burns are not created in the retina; presumably, the energy is absorbed by the retinal pigment epithelium (RPE) and stimulates reabsorption of drusen material, sparing photoreceptors from destruction. We hypothesized that autofluorescence (AF) changes would be visible after such treatment and might be sensitive to quantify RPE changes. METHODS: Twenty eyes of 13 patients with non-exudative age-related macular degeneration were studied. Forty-eight subthreshold infrared diode laser spots were applied as treatment to cause drusen regression. Before, immediately after, and 3 months after treatment, color fundus photography, fluorescein angiography (FA), and autofluorescence (AF) imaging were performed. Treated lesions were identified on overlay images of all three imaging methods. RESULTS: : The averaged sensitivity of AF imaging compared with FA was 29.6+/-28.7% versus 10.2+/-12.2% (P=0.008) at the immediate posttreatment time point and 43.5+/-28.7% versus 33.8+/-26.5% (P=0.043) at the 3-month posttreatment time point, respectively. Reduction of drusen at 3 months correlated with the detection sensitivity of AF imaging at the immediate posttreatment time point (P=0.022). CONCLUSION: Immediately after subthreshold laser treatment, AF imaging was more sensitive to detect RPE changes than FA. This suggests that noninvasive AF imaging may allow prediction of the effect of subthreshold laser treatment and might be used to titrate treatment dose.

Aged↗
PubMed2005

Lidocaine gel anesthesia for intravitreal drug administration.

PURPOSE: To describe the use of topical gel anesthesia for intravitreal injection drug delivery. METHODS: The first group (n=12) of patients is a crossover group of patients who on separate occasions received intravitreal injections after both 2% lidocaine subconjunctival injection (SC) and 2% lidocaine topical gel anesthesia using 30-gauge needle. The second group (n=16) is a consecutive group of patients who received either SC (n=8) or gel (n=8) anesthesia before intravitreal injection of triamcinolone using 27.5-gauge needle. Descriptive and numerical pain analog scale was used to assess pain sensation. RESULTS: : There was no difference in pain score between gel and SC within the first group (P=0.67, paired, nonparametric test) and no difference in pain score comparing patients who had either SC or gel anesthesia before 27.5-gauge intravitreal injections (P=0.82, unpaired t-test) in the second group. However, there were significant differences in incidence of chemosis (P<0.001) and subconjunctival hemorrhage (P<0.001) after injection versus gel anesthesia in both groups. CONCLUSION: Anesthesia with lidocaine 2% gel provides satisfactory patient comfort for administration of intravitreal injection and causes less chemosis and hemorrhage than SC anesthesia.

Administration, Topical↗