Rapid improvement of rubeosis iridis from a single bevacizumab (Avastin) injection.
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Antibodies, Monoclonal↗
Biomedical subjects
Frederick H Davidorf
Publications and source records attributed to Frederick H Davidorf.
High frequency of submicroscopic hemizygous deletion is a major mechanism of loss of expression of PTEN in uveal melanoma.
PURPOSE: Although cytogenetic aberrations at 10q have been reported in up to 27% of uveal melanomas, the role of PTEN in the pathogenesis of uveal melanoma is largely unknown. Our aim was to determine the frequency and clinical significance of PTEN alterations in uveal melanomas. PATIENTS AND METHODS: We examined PTEN expression using immunohistochemistry in 75 sporadic uveal melanomas, with an average follow-up of 89 months. Molecular cytogenetic alterations were studied using comparative genomic hybridization (CGH). Genotyping was carried out using an intragenic PTEN marker and two flanking markers. Mutational analysis of PTEN was also carried out. RESULTS: Of the 75 tumors, 12 (16%) showed no PTEN immunostaining, 32 (42.7%) showed weak to moderate staining and the remaining 31 (38.2%) showed staining similar to the normal internal controls. Using CGH, only two (15.4%) of 13 samples showed any loss of 10q. However, in the 38 tumors with informative genotyping, we found that 29 (76.3%) had loss of heterozygosity (LOH) of at least one PTEN marker, and 15 (39.5%) showed LOH of at least two markers. Mutations in the coding region of PTEN were identified in four (11.4%) of 35 tumors. Further, loss of cytoplasmic PTEN expression by immunohistochemistry was associated with shortened disease-free survival (P = .029). CONCLUSION: This is the first demonstration that PTEN is a tumor suppressor involved in uveal melanoma pathogenesis and may be associated with clinical outcome. Our data also suggest that submicroscopic deletion, but not large deletions, is the major mechanism of loss of PTEN expression in uveal melanomas.
Adult↗
Expression of vascular endothelial growth factor in uveal melanoma is independent of 6p21-region copy number.
PURPOSE: Overexpression of vascular endothelial growth factor (VEGF) and overrepresentation of the 6p region have been reported with a wide variation in uveal melanoma. The aim of the current study is to identify the frequency of copy number alteration in the 6p21 region and its correlation with the expression of VEGF in uveal melanoma. EXPERIMENTAL DESIGN: We studied 88 uveal melanomas for copy number change in the 6p region by comparative genomic hybridization and/or chromogenic in situ hybridization. Expression of VEGF protein was estimated by immunohistochemistry. In 15 tumors, VEGF mRNA expression was also studied by quantitative reverse transcription-PCR (RT-PCR) and VEGF splice variants were detected by RT-PCR. RESULTS: Copy number of the 6p21 region was successfully estimated in 37 tumors. In 10 (27%) of those, overrepresentation of the 6p21 region was detected. There was no statistically significant difference in VEGF expression between tumors with and without gain of 6p21 (P = 0.82). VEGF expression was not confined to the tumors and was also detected in the surrounding normal tissue. Expression of VEGF, detected by quantitative RT-PCR, was concordant with expression of VEGF protein. Different VEGF isoforms were expressed in different tumors with no obvious correlation with disease status. CONCLUSION: VEGF is overexpressed in a significant number of uveal melanomas. It should be noted that VEGF is not a candidate oncogene in uveal melanoma with 6p gain/amplification. VEGF overexpression other than structural amplification is probably significant in the pathogenesis of uveal melanomas, and its mechanism must be sought.
Alternative Splicing↗
Delivery of antiangiogenic and antioxidant drugs of ophthalmic interest through a nanoporous inorganic filter.
PURPOSE: We propose a novel method of administration of antiangiogenic and antioxidant drugs, with potential clinical application in the treatment of proliferative diabetic retinopathy (PDR) and age-related macular degeneration (AMD). We suggest the encapsulation of drugs in implantable sustained release devices, limited by membranes with pores in the tens of nanometers diameter range, which display a slower, quasi-linear release kinetics, and a better selectivity than other membranes. In this paper we explored the feasibility of this approach by testing in vitro several key elements of the nanofilter system: diffusion of drugs of interest, efficacy in producing desirable effects on cells, and biocompatibility of used material with some of the cells encountered in the ocular cavity. METHODS: We used an aluminum oxide filter (Anopore) with pores of 20 nm as a limiting medium for the administration of drugs. First, we induced an oxidative stress in human retinal endothelial cells (HREC) by treating them with hydrogen peroxide diffused across the filter, in the absence or in the presence of catalase. HREC attached to the culture plate, or emerging as angiogenic sprouts from aggregates embedded in collagen gels, were also exposed to vitamin C or to endostatin delivered across the nanoporous filter. Direct exposure of the cells to the agents served as positive controls. Growth of cells on the filter was considered an indication for biocompatibility. RESULTS: Catalase diffused across the nanoporous membrane counteracted the cytotoxic effect of hydrogen peroxide on HREC. We also found that vitamin C, acting directly or after diffusion across the filter, up to concentrations physiologically present in the eye, was a concentration dependent modulator of HREC's ability to survive and sprout. Additionally, we confirmed the ability of endostatin to block the growth of HREC either attached or sprouting from cell aggregates, after diffusion across the Anopore nanofilter. CONCLUSIONS: The drug delivery method based on the administration of angiostatic and antioxidant agents across the inorganic aluminum oxide nanoporous filter passed the key in vitro tests for diffusibility and biocompatibility, opening the way for medical applications.
Aluminum Oxide↗
Surgical removal vs observation for subfoveal choroidal neovascularization, either associated with the ocular histoplasmosis syndrome or idiopathic: I. Ophthalmic findings from a randomized clinical trial: Submacular Surgery Trials (SST) Group H Trial: SST Report No. 9.
OBJECTIVE: To present visual acuity findings and related outcomes from eyes of patients enrolled in a randomized trial conducted by the Submacular Surgery Trials (SST) Research Group (SST Group H Trial) to compare surgical removal vs observation of subfoveal choroidal neovascular lesions that were either idiopathic or associated with ocular histoplasmosis. METHODS: Eligible patients 18 years or older had subfoveal choroidal neovascularization (new or recurrent) that included a classic component on fluorescein angiography and best-corrected visual acuity of 20/50 to 20/800 in 1 eye ("study eye"). Patients were examined 3, 6, 12, and 24 months after enrollment to assess study outcomes and adverse events. Best-corrected visual acuity was measured by a masked examiner at the 24-month examination. A successful outcome was defined a priori as 24-month visual acuity better or no more than 1 line (7 letters) worse than at baseline. RESULTS: Among 225 patients enrolled (median visual acuity 20/100), 113 study eyes were assigned to observation and 112 to surgery. Forty-six percent of the eyes in the observation arm and 55% in the surgery arm had a successful outcome (success ratio, 1.18; 95% confidence interval, 0.89-1.56). Median visual acuity at the 24-month examination was 20/250 among eyes in the observation arm and 20/160 for eyes in the surgery arm. The prespecified subgroup of eyes with visual acuity worse than 20/100 at baseline (n = 92) had more successes with surgery; 31 (76%) of 41 eyes in the surgery arm vs 20 (50%) of 40 eyes in the observation arm examined at 24 months (success ratio, 1.53; 95% confidence interval, 1.08-2.16). Five (4%) of 111 eyes in the surgery arm subsequently had a rhegmatogenous retinal detachment. Twenty-seven (24%) of 112 initially phakic eyes in the surgery arm (none in the observation arm) had cataract surgery during follow-up, all among patients older than 50 years. Recurrent choroidal neovascularization developed by the 24-month examination in 58% of surgically treated eyes. CONCLUSIONS: Overall, findings supported no benefit or a smaller benefit to surgery than the trial was designed to detect. Findings support consideration of surgery for eyes with subfoveal choroidal neovascularization and best-corrected visual acuity worse than 20/100 that meet other eligibility criteria for the SST Group H Trial. Other factors that may influence the treatment decision include the risks of retinal detachment, cataract among older patients, and recurrent choroidal neovascularization and the possibility that additional treatment will be required after submacular surgery.
Adult↗
Juxtafoveal telangiectasis-a name change?
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Female↗
Custom-made "Nag" eye plaques for 125I brachytherapy.
PURPOSE: To report our experience in treating medium-size ocular melanomas with custom-made "Nag" eye plaques. METHODS: Seventy-eight patients with medium-size ocular melanomas were treated with plaques of 0.6-mm-thick, 18k gold with a radius of curvature of 12 mm to conform to the curvature of the eyeball. These plaques were custom-made in various sizes and shapes to encompass the base of the tumor and a 1-mm margin on all sides. Apertures in three wings of these plaques allowed sutures to be easily placed to hold the plaques onto the sclera. A dose of 100 Gy (before TG-43) or 85 Gy (after TG-43) was delivered with (125)I in 4 days. The dose was prescribed to the periphery of tumor at the level of tumor apex to ensure that the entire tumor volume received at least this dose. RESULTS: The median follow-up was 49 months (range 8-112 months). The progression-free survival (Kaplan-Meier method), overall survival, and disease-specific survival at 5 years were 93%, 86%, and 97%, respectively. Fifty of 78 (64%) patients retained useful visual acuity (20/200 or better). Thirty-one of 78 (40%) patients developed retinopathy or papillopathy. In the subgroup of 22 patients with tumor distance < or =2 mm from optic disc or macula, 12 patients (54%) developed retinopathy or papillopathy. Only 7 of these patients (32%) had useful vision (20/200 or better). Short distance to optic disc or macula was associated with significantly poor visual acuity and moderate to severe retinopathy or papillopathy (ANOVA, p = 0.004 and p = 0.002, respectively). CONCLUSION: Our experience suggests that custom-made Nag plaque brachytherapy can control medium-size choroidal melanoma and that a 1-mm, rather than the standard 2-mm, minimum margin is sufficient when this plaque and prescription methods are used. Patients with tumors close (< or =2 mm) to optic disc or macula have a significantly poorer visual outcome.
Brachytherapy↗
Management of medulloepithelioma of the ciliary body with brachytherapy.
PURPOSE: To report a case of an adult with a ciliary body mass diagnosed as a medulloepithelioma by fine-needle aspiration, confirmed by tissue biopsy, and successfully treated with brachytherapy. DESIGN: Interventional case report. METHODS: A 23-year-old white woman presented with a large mass originating in the ciliary body of the left eye. The mass, which measured 6 x 5 x 7.6 mm, was at the upper limits for resection. Treatment with iodine-125 brachytherapy (4,648 cGy) was employed to debulk the mass before eyewall resection. RESULTS: The elevation of the mass by ultrasonography 5 months after brachytherapy was 3.9 mm with no evidence of growth during the 18-month follow-up period. CONCLUSION: We report a case in which a ciliary body medulloepithelioma treated with brachytherapy had a favorable response through 18 months of follow-up after treatment. This is a single case report, and longer follow-up is necessary before treatment efficacy can be fully evaluated.
Adult↗