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Biomedical subjects

Paul Sternberg

Publications and source records attributed to Paul Sternberg.

30 records · Page 2Linked to original sources
PubMed2003

Clinicopathologic findings in choroidal melanomas after failed transpupillary thermotherapy.

PURPOSE: To review the clinicopathologic features of eyes enucleated after failed transpupillary thermotherapy. DESIGN: Retrospective review. METHODS: Pathology reports in the L.F. Montgomery Laboratory between 1998 and 2002 were searched for enucleated eyes with choroidal melanoma that had been treated only by transpupillary thermotherapy (TTT) prior to enucleation. The clinical features of the patients, including ultrasonography examination, were reviewed and compared with the pathologic findings. RESULTS: Seven eyes from seven patients had been enucleated, representing 8% of eyes treated with TTT at our institute during the period studied. The primary indication for enucleation was tumor growth. The melanomas tended to grow laterally, with minimal if any increase in thickness. Five of the seven eyes histologically demonstrated extrascleral extension, which was detected by ultrasonography prior to enucleation in only one of those eyes. CONCLUSIONS: Choroidal melanoma may continue to grow along a path of least resistance after TTT. The melanoma may extend laterally in the choroid and through emissary canals. Early extrascleral extension may be difficult to detect by ultrasonography.

Adult↗
PubMed2003

The prognostic significance of a system for classifying mechanical injuries of the eye (globe) in open-globe injuries.

PURPOSE: The aim of this study was to determine the prognostic significance of a previously published system for classifying mechanical injuries of the eye (globe) in open-globe injuries. METHODS: The medical records of 150 patients with open-globe injuries identified from an established institutional database were retrospectively reviewed to classify all injuries at presentation by the four specific variables of the classification system: type of injury, defined by the mechanism of injury; grade of injury, defined by visual acuity in the injured eye at initial examination; pupil, defined as the presence or absence of a relative afferent pupillary defect in the injured eye; and zone of injury, defined by the location of the eye-wall opening. Final visual outcomes for these injuries were also recorded. Logistic regression models were used to analyze the data and to determine whether relationships existed between the specific classification variables and final visual acuity in the injured eyes. RESULTS: All four classification variables were significant predictors of visual outcome. When adjusted for the other variables, grade and pupil were the most significant predictors of final visual acuity. CONCLUSION: This system for classifying mechanical injuries of the eye appears to be prognostic for visual outcomes in open-globe injuries. In particular, the measurement of visual acuity and testing for a relative afferent pupillary defect at the initial examination should be performed in all injured eyes because of their relative prognostic significance.

Adult↗
PubMed2002

Redox analysis of human plasma allows separation of pro-oxidant events of aging from decline in antioxidant defenses.

Oxidative stress is a component of diseases and degenerative processes associated with aging. However, no means are available to assess causative oxidative events separately from decline in function of protective antioxidant systems. Previous studies show that ongoing oxidative processes maintain plasma cysteine/cystine redox at a value that is more oxidized than the antioxidant glutathione/glutathione disulfide (GSH/GSSG) system, suggesting that redox analysis of these plasma thiols could allow separate evaluation of an increase in oxidative events from a decline in antioxidant function. The present study uses measurement of cysteine/cystine and GSH/GSSG redox in plasma of 122 healthy individuals aged 19-85 years to determine whether thiol-disulfide redox changes occur with age. The results show a linear oxidation of cysteine/cystine redox state with age at a rate of 0.16 mV/year over the entire age span. In contrast, GSH/GSSG redox was not oxidized prior to 45 years and subsequently was oxidized at a nearly linear rate of 0.7 mV/year. These data suggest that there is a continuous, linear increase in oxidative events throughout adult life but that the capacity of the GSH antioxidant system is maintained until 45 years and then declines rapidly. The data further suggest that redox states of cysteine/cystine and GSH/GSSG provide an approach to clinically distinguish between increased causative oxidative events and decreased GSH antioxidant function. In principle, such analyses can be used to assess efficacy of intervention strategies against oxidative stress prior to or early after onset of clinical symptoms in aging and age-related disease.

Adolescent↗
PubMed2002

Macrophage and retinal pigment epithelium expression of angiogenic cytokines in choroidal neovascularization.

PURPOSE: To determine the expression of angiogenic cytokines in macrophages and retinal pigment epithelium cells in choroidal neovascularization (CNV). METHODS: Ten surgically-excised subfoveal CNV specimens and ten eye bank eyes with subfoveal CNV were routinely processed, serially sectioned, and immunostained for factor VIII (F8), CD68 (KP1), cytokeratin 18 (CK18), vascular endothelial growth factor (VEGF), tissue factor (TF), and monocyte chemotactic protein (MCP). The CNV was classified as "inflammatory active" (more inflammation than fibrosis) or "inflammatory inactive" (morefibrosis than inflammation). The immunostaining was graded as none, mild (+), moderate (++), or heavy (+++). Five additional surgically-excised CNV specimens were dual labeled with CK18/MCP or CD68/TF and confocal scanning laser microscopy was performed. RESULTS: Vascular endothelium, macrophages, and RPE expressed F8, KP1, and CK18 respectively. Macrophages expressed + to ++ VEGF and ++ to +++ TF; RPE expressed ++ to +++ VEGF and ++ to +++ MCP. Staining for angiogenic cytokines was stronger in inflammatory active versus inflammatory inactive CNV. RPE dual labeled for CK18/MCP and macrophages dual labeled for CD68/TF. CONCLUSIONS: This study shows that RPE cells express MCP, a cytokine involved with macrophage recruitment, and that macrophages express TF in CNV. Macrophages and RPE express VEGF, thus perpetuating angiogenesis. TF is involved with fibrin formation and provides a scaffold effect for growth of the CNV complex. CNV likely represents a dynamic process with inflammatory active and inflammatory inactive (involutional) stages.

Adult↗
PubMed2002

Retinal pigment epithelial changes after macular hole surgery with indocyanine green-assisted internal limiting membrane peeling.

PURPOSE: To report the results of macular hole surgery using indocyanine green to improve visualization and facilitate peeling of the internal limiting membrane. METHODS: A retrospective noncomparative review of a consecutive series of 22 patients (22 eyes) who underwent macular hole repair using indocyanine green to facilitate visualization of the internal limiting membrane was performed. One patient was excluded because of a history of a rhegmatogenous retinal detachment. All patients underwent a three-port pars plana vitrectomy with internal limiting membrane peeling. Indocyanine green (0.1% solution) was used to assist in the visualization of the internal limiting membrane. The main outcome measures were postoperative visual acuity, macular hole status, and postoperative retinal pigment epithelial changes. RESULTS: In 21 eyes, the median preoperative best-corrected visual acuity was 20/200 (range, 20/60 to counting fingers at 5 feet). The median postoperative visual acuity was 20/400 (range, 20/60-1/200) with an average follow-up of 13 weeks. The macular hole was closed in 18 eyes (86%) at the most recent follow-up. Ten eyes were found to have atrophic retinal pigment epithelium changes in the area of the previous macular hole. CONCLUSIONS: Indocyanine green assists in visualization of the internal limiting membrane in macular hole surgery. In our series, 10 eyes had unusual atrophic changes in the retinal pigment epithelium at the site of the previous macular hole, or in the area where the indocyanine green solution would have had direct access to the bare retinal pigment epithelium cells. Although the use of indocyanine green improves visualization and assists with peeling of the internal limiting membrane, the safety and potential toxicity of indocyanine green to the retinal pigment epithelium require further investigation.

Aged↗
PubMed2002

Photodynamic therapy of subfoveal choroidal neovascularization with verteporfin in the ocular histoplasmosis syndrome: one-year results of an uncontrolled, prospective case series.

OBJECTIVE: To evaluate the safety and effect on visual acuity of photodynamic therapy with verteporfin (Visudyne, Novartis AG) in patients with subfoveal choroidal neovascularization (CNV) secondary to the ocular histoplasmosis syndrome (OHS). DESIGN: Open-label, three-center, noncomparative prospective case series. PARTICIPANTS: OHS patients with subfoveal CNV lesions no larger than 5400 micro m in greatest linear dimension (GLD) with classic or occult CNV extending under the geometric center of the foveal avascular zone and best-corrected visual acuity letter score of 73 to 34 (approximate Snellen equivalent 20/40-20/200). METHODS: Twenty-six patients received verteporfin (6 mg/m(2)) infused IV over 10 minutes. Fifteen minutes after the start of infusion, a laser light at 689 nm delivered 50 J/cm(2) at an intensity of 600 mW/cm(2) over 83 seconds using a spot size with a diameter 1000 micro m larger than the GLD of the lesion. At 3-month follow-up examinations, retreatment with the same regimen was applied if angiography showed fluorescein leakage. Safety assessments were also made. MAIN OUTCOME MEASURES: Visual function measurements were the changes from baseline in visual acuity and contrast sensitivity scores and the proportion of patients who, based on best-corrected visual acuity scores, (1) gained 7 or more letters, (2) lost 8 or more letters, and (3) lost 15 or more letters. RESULTS: One patient was omitted from the study at the month 3 examination for not meeting the visual acuity eligibility requirements at baseline. By the month 12 examination, but excluding any retreatment at that visit, patients had received an average of 2.9 treatments of a maximum of 4 possible treatments. The month 12 median improvement from baseline in visual acuity of the remaining 25 patients was 7 letters, and median contrast sensitivity improved by 2 letters. Median visual acuity improvement was also 7 letters when three patients, who failed to meet all photographic eligibility requirements at baseline, were excluded. At the month 12 examination, 14 (56%) patients gained 7 or more letters of visual acuity from baseline, whereas 4 (16%) patients lost 8 or more letters, of which 2 (8%) lost 15 or more letters. No serious systemic or ocular adverse events were reported. CONCLUSIONS: Median visual acuity improved after verteporfin therapy for at least 1 year in a small uncontrolled prospective case series of patients with subfoveal CNV caused by OHS. Verteporfin therapy seemed to be safe and well tolerated in these patients. Two-year data from this study will provide important, additional information on the safety and effect of verteporfin therapy for the treatment of subfoveal CNV secondary to OHS.

Adult↗
PubMed2002

Submacular surgery trials update.

Submacular surgery is a method of therapy for subfoveal CNV from multiple causes. It was first reported in the late 1980s. Since then, refinements in patient selection and surgical technique have reduced complications and made it a viable alternative to existing treatments and natural history for this condition. The Submacular Surgery Trials (SST) is a series of prospective, randomized, multicenter clinical trials designed to evaluate submacular surgery for exudative and hemorrhagic subfoveal CNV from AMD and for exudative subfoveal CNV from OHS and idiopathic causes. Recruitment has been completed for these trials, and the DSMC is continuously monitoring safety and efficacy and evaluating any modifications of study design to accommodate new therapies for subfoveal CNV.

Choroidal Neovascularization↗
PubMed2002

Increased oxidant-induced apoptosis in cultured nondividing human retinal pigment epithelial cells.

PURPOSE: To determine whether long-term cultured nondividing human retinal pigment epithelial (hRPE) cells are sensitive to oxidant-induced apoptosis and whether the Fas pathway is involved in the process. METHODS: Confluent hRPE cells were maintained for 2 to 3 months in the basal medium (DMEM containing 2% fetal bovine serum) with one medium change per week. DNA synthesis was measured by incorporation of bromodeoxyuridine (BrdU) and the cell cycle was analyzed by flow cytometry. Intracellular glutathione (GSH) and glutathione disulfide (GSSG) were measured by HPLC. Apoptosis was triggered with the oxidant tert-butylhydroperoxide (tBH), recombinant soluble Fas ligand (sFasL), or agonistic anti-Fas antibody (CH-11). Cell viability was assessed by tetrazolium salt (WST-1) assay, and apoptosis was determined by measuring DNA cleavage or phosphatidylserine exposure. FasL and Fas proteins were detected by flow cytometry and Western blot. FasL and Fas transcripts were analyzed by RT-PCR. RESULTS: After incubation in basal medium for more than 2 months, hRPE cells were largely nondividing and accumulated autofluorescent granules identified by electron microscopy to be lysosomes. Compared with proliferating hRPE cells, the nondividing cells had lower intracellular GSH, GSSG, and GSH/GSSG and a more oxidized redox potential (E(h)). Downregulation of Fas but upregulation of FasL was observed in these cells. The nondividing hRPE cells appeared more susceptible to tBH-induced apoptosis. Similar to proliferating hRPE cells, the apoptosis induced by tBH was preceded by induction of FasL, and antioxidants inhibited both FasL increase and apoptosis. Apoptosis was also inhibited with the antagonistic anti-Fas antibody ZB4. However, the nondividing hRPE cells had decreased sensitivity to apoptosis triggered by sFasL or CH-11. CONCLUSIONS: Long-term hRPE culture created cells that were nondividing and accumulated autofluorescent granules. The increased sensitivity to tBH-induced apoptosis in these cells was associated with intracellular oxidation and upregulation of FasL. These results suggest that an increase in FasL may contribute to the vulnerability of nondividing hRPE cells to oxidant-induced apoptosis.

Apoptosis↗
PubMed2002

Protection of retinal pigment epithelial cells from oxidative damage by oltipraz, a cancer chemopreventive agent.

OBJECTIVE: To determine whether oltipraz (4-methyl-5-pyrazinyl-3H-1,2-dithiole-3-thione) protects against oxidative injury in cultured human retinal pigment epithelial (hRPE) cells. METHODS: Primary cultured hRPE cells were incubated with various concentrations of oltipraz followed by treatment with the chemical oxidant tert-butylhydroperoxide (tBH). Cell viability was assessed by release of lactate dehydrogenase (LDH) and cleavage of WST-1. Intracellular and mitochondrial levels of glutathione (GSH) were measured by HPLC. Glutathione S-transferase (GST), NADPH-quinone reductase (NQR), and glutathione peroxidase (GPx) were measured by specific enzyme activity assays. RESULTS: Treatment of hRPE cells with oltipraz inhibited tBH-induced cell death in a concentration-dependent manner with significant inhibition at 50 micro M. Olitpraz (50 micro M) increased GSH levels in hRPE cells by approximately 18% and in hRPE mitochondrial fractions by approximately 50% after 24 hours of exposure. Treatment with oltipraz increased GST and NQR activities by approximately 21% and 11%, respectively. CONCLUSIONS: Oltipraz protects hRPE cells against tBH induced injury. The mechanism of protection is likely to include increased cellular and mitochondrial GSH levels and induction of detoxification enzymes, including GST and NQR. Dietary supplementation with oltipraz or other dithiolethiones may help protect the hRPE against oxidant induced injury.

Anticarcinogenic Agents↗