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Biomedical subjects

W R Freeman

Publications and source records attributed to W R Freeman.

At least 37 records · Page 2Linked to original sources
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↗
PubMed2000

Systemic toxicity of topical and periocular corticosteroid therapy in an 11-year-old male with posterior uveitis.

PURPOSE: To report a case of systemic corticosteroid toxicity resulting from topical and periocular therapy. METHODS: Treatment and follow-up of an 11-year-old male with uveitis are illustrated. Initial presentation of the patient was bilateral iridocyclitis, for which he was treated with prednisolone acetate 1% every 2 hours for 6 months. Subsequently, posterior uveitis developed, necessitating posterior subtenon injections. RESULTS: After initial topical corticosteroid therapy, the patient developed a cushingoid habitus accompanied by increased lanugo hair, acanthosis nigricans, posterior subcapsular lens opacities, and increased intraocular pressure. Cushingoid stigmata worsened after administration of posterior subtenon injection of corticosteroids. The patient's truncal obesity worsened, and his linear growth stopped. CONCLUSIONS: Systemic toxic effects may develop as a result of topical and local use of ophthalmic corticosteroid preparations in susceptible patients.

Acanthosis Nigricans↗
PubMed2000

Long-term posterior and anterior segment complications of immune recovery uveitis associated with cytomegalovirus retinitis.

PURPOSE: To identify and describe long-term posterior and anterior segment complications of immune recovery uveitis in patients with inactive cytomegalovirus retinitis who are undergoing highly active antiretroviral therapy-mediated recovery of immune function. METHODS: A prospective cohort study at a university medical center. Twenty-nine eyes of 21 patients with immune recovery uveitis and inactive cytomegalovirus retinitis were followed for 14.5 to 116 weeks (median, 43 weeks) after diagnosis of immune recovery uveitis. RESULTS: Nine eyes of nine patients developed visually important complications involving the posterior segment, anterior segment, or a combination of both. Posterior segment complications included severe proliferative vitreoretinopathy in three eyes and spontaneous vitreous hemorrhage from avulsion of a blood vessel secondary to contraction of the inflamed vitreous in one eye. Proliferative vitreoretinopathy recurred in all cases after surgery, severely compromising the visual outcome. Anterior segment complications included posterior subcapsular cataracts with vision decrease in five eyes and persistent anterior chamber inflammation after cataract extraction, resulting in posterior synechiae and large visually important lens deposits in three eyes. CONCLUSION: Persistent inflammation in immune recovery uveitis may lead to vision-threatening complications, such as proliferative vitreoretinopathy, posterior subcapsular cataracts, and severe postoperative inflammation. Immune recovery uveitis is a chronic inflammatory syndrome that may result in complications months to years after the onset of inflammation.

Adult↗
PubMed2000

Highly active antiretroviral therapy-related immune recovery in AIDS patients with cytomegalovirus retinitis.

OBJECTIVE: To characterize cytomegalovirus (CMV) retinitis in human immunodeficiency virus (HIV)-infected patients who demonstrate immune recovery while receiving highly active antiretroviral therapy (HAART). DESIGN: Consecutive, noncomparative case series. PARTICIPANTS: Twenty-two HIV-positive patients, from two institutions, with a history of CMV retinitis, and with elevated CD4 cell counts after HAART. MAIN OUTCOME MEASURES: Duration of healed CMV retinitis without anti-CMV therapy, CD4 cell count, and HIV viral load. INTERVENTION: Discontinuation of anti-CMV therapy after persistent elevation of CD4 cell count over 50 cell/mm3 (median, 161/mm3; range, 85-408/mm3). RESULTS: The median period of healed CMV retinitis without anti-CMV therapy was 72 weeks (range, 33-116 weeks). Nineteen of 22 patients were still healed without anti-CMV therapy at study end. The three patients with CMV retinitis progression simultaneously had HAART, fail with CD4 cell counts of 37, 35, and 47/mm3. CONCLUSIONS: HIV-positive patients with CMV retinitis, who demonstrate a sustained HAART-induced elevation of CD4 cell count on two consecutive counts 3 months apart and whose retinitis remains healed on anti-CMV therapy for greater than 4 months, are likely to remain healed if the anti-CMV therapy is withdrawn. It is important to monitor these patients with indirect ophthalmoscopy because HAART failure may occur and allow CMV retinitis reactivation.

AIDS-Related Opportunistic Infections↗
PubMed2000

Prevalence, correlates, and natural history of epiretinal membranes surrounding idiopathic macular holes. Virectomy for Macular Hole Study Group.

OBJECTIVE: To report on the prevalence, correlates, and natural history of epiretinal membranes (ERM) in eyes with stage II or III/IV macular holes. DESIGN: A subgroup analysis arising from a multicentered, controlled, randomized clinical trial. SETTING: Community and university-based ophthalmology clinics. PATIENTS: Two hundred twenty four eyes with stage II or III/IV macular holes. INTERVENTIONS: No intervention for 100 eyes randomly assigned to observation. OUTCOME MEASURES: Grade of ERM determined by stereoscopic examination of fundus photographs at baseline and at 3, 6, 12, and 24 months of follow-up. RESULTS: The prevalence of ERM was 65% (145 of 224 eyes), was greater in pseudophakic than in phakic eyes (80% vs. 63%, P = 0.10), and increased with increasing severity of the hole (P < 0.0001). Stage III/IV eyes with ERM had a significantly larger hole size than did eyes without ERM (P < 0.01); however, no association between presence of ERM and visual acuity was found (P > 0.5). In the 100 phakic eyes that were randomly assigned to observation, there was a significant increase in the severity of ERM over follow-up (P < 0.0001). CONCLUSIONS: ERM are common in eyes with full-thickness idiopathic macular holes. Although ERM prevalence increases with severity and size of the macular hole, the presence of ERM are not closely correlated with visual acuity. These factors may be important in considering the removal of ERM during vitrectomy for macular hole.

California↗
PubMed2000

Correlation between static automated and scanning laser entoptic perimetry in normal subjects and glaucoma patients.

OBJECTIVE: To compare the effectiveness of scanning laser entoptic perimetry with static automated perimetry as a noninvasive instrument for screening for glaucomatous damage in visually asymptomatic subjects within the central 60 degrees (diameter) of vision. DESIGN: A masked cross-sectional study comparing entoptic perimetry to achromatic threshold perimetry. PARTICIPANTS: Twenty-three subjects and controls from the Sharp Rees-Stealy Hospital and the Shiley Eye Center at the University of California, San Diego. TESTING: Virtual reality-based entoptic perimetry was compared with achromatic threshold perimetry. MAIN OUTCOME MEASURES: For each testing session, we compared the presence of a disturbance in the entoptic perimetry stimulus with the presence of defects in visual function as measured by Humphrey automated visual field perimetry. RESULTS: Scanning laser entoptic perimetry reasonably estimates the overall visual field loss for moderate-to-severe scotomas as measured by the pattern deviation in standard visual field perimetry. Scanning laser entoptic perimetry has a sensitivity from 27% to 90% and a specificity from 50% to 100% for screening moderate-to-severe visual field defects caused by glaucoma within the central 60 degrees diameter of vision. CONCLUSIONS: Scanning laser entoptic perimetry may be an effective and inexpensive screening test in hospitals and community clinics for diagnosing visual field loss caused by glaucoma.

Cross-Sectional Studies↗
PubMed2000

Choroidal melanoma microcirculation with confocal indocyanine green angiography before and 1 year after radiation brachytherapy.

PURPOSE: The authors previously demonstrated that confocal indocyanine green (ICG) angiography is capable of imaging the microcirculation of choroidal melanomas. The purpose of this study is to report their observations regarding the response of the microcirculation using confocal ICG at 1 year after radiation brachytherapy. METHODS: Thirteen patients with unilateral choroidal melanoma were examined once before and several times up to 1 year after radiation brachytherapy (Iodine-125 or Ruthenium-106 plaque). At each visit, a complete ophthalmologic examination including standardized echography and fluorescein and ICG angiography was obtained, the latter using a confocal scanning laser ophthalmoscope. RESULTS: In 10 patients (77%), the tumor microcirculation changed considerably within 1 year after treatment. Distortion, thickening, thinning, and complete obliteration of vessels could be observed. In the other 3 patients (23%), no changes in the microcirculation were noticed within the observation period. CONCLUSIONS: Follow-up with confocal ICG of choroidal melanomas after treatment with local radiation brachytherapy allows for visualization of the microcirculation reaction following radiation brachytherapy. This provides the clinician with additional information for the posttreatment monitoring of these patients. Confocal ICG might also be a useful tool to monitor the effects of future antiangiogenesis-based tumor therapies in choroidal melanomas.

Adult↗
PubMed2000

Characterization of reactivation of cytomegalovirus retinitis in patients healed after treatment with highly active antiretroviral therapy.

PURPOSE: To delineate the immune parameters associated with reactivation of cytomegalovirus (CMV) retinitis in patients for whom highly active antiretroviral therapy (HAART) was not successful. METHODS: Prospective, longitudinal observational study of a cohort of 102 patients with CMV retinitis treated with HAART and being followed up at the AIDS Ocular Research Unit of the University of California, San Diego from November 1995 to November 1998. The study included serial clinical and fundus photographic examinations with CD4 T-lymphocyte counts and HIV viral load measurements. RESULTS: Forty-seven of the 102 patients with CMV retinitis responded to HAART. Thirty-five of the patients were successfully withdrawn from anti-CMV therapy. During a median follow-up of 74.71 weeks (range, 4.86-144 weeks) after discontinuation of anti-CMV therapy, four patients experienced a reactivation of CMV retinitis. In each case, the CD4 count decreased before reactivation to a median of 31.5 cells/mm3 (mean, 31.25 cells/mm3; range, 23-39 cells/mm3). The association between the CD4 count decreasing to less than 50 cells/mm3 and reactivation of CMV retinitis was statistically significant (P < 0.0003). CONCLUSION: Four patients treated with HAART experienced reactivation of CMV retinitis as their CD4 count decreased. The threshold CD4 count below which reactivation of CMV retinitis occurred in patients for whom HAART was not successful appeared to be 50 cells/mm3. Despite an initial response to HAART, patients are still at risk for reactivation of CMV retinitis if their CD4 count decreases to less than 50 cells/mm3. The HIV viral load did not appear to predict CMV reactivation.

AIDS-Related Opportunistic Infections↗
PubMed2000

Intravitreal toxicology and duration of efficacy of a novel antiviral lipid prodrug of ganciclovir in liposome formulation.

PURPOSE: To evaluate the intraocular safety and antiviral treatment efficacy of the sustained lipid prodrug of ganciclovir, 1-O-hexadecylpropanediol-3-phospho-ganciclovir (HDP-P-GCV), as an intravitreal injectable drug system for viral retinitis. METHODS: HDP-P-GCV was synthesized by coupling 1-O-hexadecyl-propanediol-3-phosphate to either free hydroxyl of ganciclovir in pyridine with dicyclohexylcarbodiimide as catalyst. The compound was formulated into liposomes. The antiviral activity was assessed by DNA reduction in vitro, and intraocular safety was assessed by ophthalmoscopy, electrophysiology, and histology after intravitreal injections, with resultant intravitreal concentrations of 0.2, 0.632, 1.12, and 2 mM. The treatment efficacy was evaluated by simultaneous intravitreal injection of HDP-P-GCV and herpes simplex virus type 1 (HSV-1) or by intravitreal injection of HDP-P-GCV at various times before HSV-1 intravitreal inoculation. Retinitis was scored with ophthalmoscopy and compared with controls. RESULTS: In vitro, the IC50 of HDP-P-GCV against HSV-1 and human cytomegalovirus (HCMV) infected cells was 0.02 and 0.6 microM, respectively. In rabbits in vivo, HDP-P-GCV dispersed evenly and maintained a good vitreous clarity at all doses except 2 mM final intravitreal concentration. Although cataracts were observed in some eyes at the higher doses, they were not observed in eyes with 0.2 mM final intravitreal concentration. No other indications of ocular toxicity were observed. Intravitreal injection of HDP-P-GCV with resultant 0.2 mM intravitreal concentration in the HSV-1 retinitis rabbit model demonstrated a complete protection of the retina with the simultaneous treatment strategy and a 4 (P = 0.03) to 6-(P = 0.058) week significant protection of retina with the pretreatment strategies when compared with ganciclovir or blank liposome controls. CONCLUSIONS: In the rabbit model of HSV-1 retinitis HDP-P-GCV acts as a long-lasting intravitreal injectable anti-CMV or anti-HSV compound. This self-assembling liposome system could be applicable for many compounds available for intraocular diseases.

Animals↗
PubMed2000

The effect of prinomastat (AG3340), a potent inhibitor of matrix metalloproteinases, on a subacute model of proliferative vitreoretinopathy.

PURPOSE: To determine the efficacy of prinomastat (AG3340), a synthetic inhibitor of matrix metalloproteinase, in the treatment of experimental proliferative vitreoretinopathy (PVR) induced by intravitreal dispase injection. METHODS: One eye each of 53 New Zealand white rabbits was injected in the vitreous cavity with 0.07 unit of dispase to induce PVR. One week after PVR induction, 53 rabbits were randomized (27:26) to receive 0.5 mg prinomastat or the vehicle of the drug (acidified water) intravitreally every two weeks. The scores of PVR severity (scale of 1-5) were graded to compare the prinomastat-treated animals with the control group. RESULTS: The average PVR scores in the treatment and control groups were 2.62 and 3.57 respectively (p = 0.038; Wilcoxon rank sum). Clinically significant PVR with retinal detachment (PVR > or = grade 3) developed in 76% of rabbits in the control group versus 51% of rabbits treated with prinomastat. CONCLUSIONS: Intravitreally administered prinomastat decreased development of PVR in an experimental model which made use of dispase to induce PVR.

Animals↗
PubMed1999

A multicentered clinical study of serum as adjuvant therapy for surgical treatment of macular holes. Vitrectomy for Macular Hole Study Group.

OBJECTIVE: To evaluate and compare the risks and benefits of autologous serum as an adjuvant therapy in macular hole surgery for stage 3 or 4 macular holes. METHODS: Comparison of 2 consecutive (nonrandomized) cohorts using standardized methods for the determination of hole size and for surgical procedures, and using the same study surgeons. The serum cohort consisted of 106 eyes using autologous serum as an adjuvant, and the no serum cohort consisted of 58 eyes without adjuvants. The primary end point was the closure of the macular hole as determined by the 6-month fundus photographs. Secondary end points included the number and types of postoperative complications. Comparison in outcomes between the 2 cohorts used chi2 and logistic regression procedures, adjusting for preoperative differences between the study cohorts. RESULTS: At 6 months, the (unadjusted) rate of hole closure was significantly greater for the eyes treated with serum than for the eyes not treated with serum (90 [85%] of 106 vs. 40 [69%] of 58, P = .04). However, after adjusting for preoperative differences in hole diameter and the prevalence of epiretinal membranes, no overall difference in hole closure rates due to serum was found (P = .44). In contrast, benefit due to serum for large holes (diameter >573 microm) was seen (12 [75%] of 16 vs 13 [57%] of 23, P = .04). No differences in complication rates were found between the cohorts. CONCLUSIONS: Any beneficial effect of serum used as an adjuvant to macular hole surgery is small, and, if present, the beneficial effect may be limited to larger holes. A randomized, prospective, controlled study in larger macular holes is needed.

Adult↗
PubMed1999

The utility of entoptic perimetry as a screening test for cytomegalovirus retinitis.

OBJECTIVE: To determine the sensitivity and specificity of entoptic perimetry as a noninvasive test for detecting retinal damage due to peripheral cytomegalovirus (CMV) retinitis. DESIGN: A masked study comparing entoptic perimetry with fundus photography under 4 experimental conditions (determined by increasing pixel sizes) on 2 separate testing sessions. SETTING: Acquired immunodeficiency syndrome Ocular Research Unit at the University of California, San Diego. PATIENTS: Twenty-four human immunodeficiency virus-positive and 8 human immunodeficiency virus-negative subjects; 21 eyes with documented CMV retinitis, and 26 eyes that were retinitis free. MEASUREMENTS: For each testing session, screening method, and condition, the presence of CMV retinitis was determined for each meridian (i.e., clock hour), each quadrant (consisting of 3 meridians), and each eye (consisting of all meridians); the amount of retinitis was defined as the percentage of meridians or quadrants with CMV retinitis. RESULTS: Entoptic perimetry was as sensitive and specific as fundus photography in determining the presence of CMV retinitis. Determination of the amount of CMV retinitis tended to be underestimated by perimetry for larger pixel sizes. CONCLUSION: Entoptic perimetry may be an effective and inexpensive alternative to fundus photography for CMV retinitis in hospitals and community clinics.

AIDS-Related Opportunistic Infections↗