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Objectives: To determine whether expression of thrombospondin-1 (TSP1), an endogenous inhibitor of angiogenesis, is downregulated during progression of uveal melanoma and whether administration of TSP1 and/or its antiangiogenic peptides attenuate tumor growth. Methods: Tyrosinase-SV40 T-antigens (Tyr Tag) transgenic mice were used for evaluation of TSP1 expression during tumor progression using immunohistological methods. The therapeutic potential of TSP1 on tumor progression was evaluated either by crossing Tyr Tag mice with a line of transgenic mice overexpressing TSP1 in the eye or by administration of TSP1-mimetic peptide with known antiangiogenic, antitumor activity. Tumor areas were measured in histological sections using Optima software (Media Cybernetics, Inc). Results: The Tyr Tag tumors from 3-week-old mice showed significant TSP1 expression, which was dramatically downregulated in tumors from 12-week-old mice. Furthermore, the development and progression of tumor was significantly delayed in Tyr Tag TSP1 transgenic mice or Tyr Tag mice receiving TSP1-mimetic peptide (100 mg/kg/d). Conclusions: Expression of TSP1 was decreased with the angiogenic switch during progression of uveal melanoma, and TSP1 and/or its antiangiogenic peptides were effective in attenuation of tumor growth. Clinical Relevance: Modulation of TSP1 expression and/ or activity may be beneficial in treating uveal melanoma. [ABSTRACT FROM AUTHOR]

Objective: To investigate a correlation between the severity of histologic changes of the Descemet membrane in patients with Fuchs endothelial dystrophy and the best corrected visual acuity (VA) after Descemet membrane- stripping automated endothelial keratoplasty (DSAEK). Methods: In a retrospective study design, we created a histologic grading system based on common characteristics observed histologically among 92 DSAEK specimens sent to the University of Wisconsin Eye Pathology Laboratory with a clinical diagnosis of Fuchs dystrophy from 3 separate corneal surgeons. Cases were graded as mild, moderate, or severe on the basis of guttae dispersion, presence of a laminated Descemet membrane, presence of embedded guttae, and density of guttae. Regression models were built to study the relationship among preoperative VA, histologic findings, and best corrected VA 6 months and 1 and 2 years after DSAEK. Results: No correlation was found between the severity of histologic changes of Descemet membrane and preoperative VA. However, a correlation was noted between the preoperative and final VA. Cases with a laminated Descemet membrane but no embedded guttae (n=8) appeared to be less responsive to DSAEK. Otherwise, the severity of histologic changes of Descemet membrane observed in patients with Fuchs corneal dystrophy after DSAEK did not show a statistically significant correlation with final VA. Conclusions: Our analysis fails to show an inverse relationship between the severity of histologic changes of the Descemet membrane and the best-corrected VA of at least 20/40 after DSAEK for Fuchs endothelial dystrophy. However, in a subset of patients with Fuchs dystrophy who develop a laminated Descemet membrane without embedded guttae, the visual recovery after DSAEK is less than expected. The laminated architecture of Descemet membrane without embedded guttae may facilitate separation between the membrane layers and, thus, incomplete removal of the recipient's Descemet membrane during DSAEK, which may then limit the postoperative visual outcome. [ABSTRACT FROM AUTHOR]

Presents a list of reviewers who assisted the editorial board of the "Archives of Ophthalmology" for 2004. Mark Abelson; Gary Abrams; Anthony P. Adamis; Anita Agarwal; Eduardo Alfonso.

Objective: To study the effectiveness of the vitamin D analogue 1α-hydroxyvitamin D2 (1α-OH-D2) in inhibiting ocular tumor growth in transgenic ‘Tyr-Tag’ mice that developed pigmented ocular tumors produced with the simian virus 40 T and t antigens under the control of the mouse tyrosinase gene. These animals develop pigmented intraocular tumors primarily from the retinal pigment epithelium that closely resemble the histologic features and growth pattern of human choroidal melanoma. Methods: A total of 73 Tyr-Tag transgenic mice between 6 and 7 weeks old were randomly assigned by sex and litter to 3 treatment groups to receive 0.05 μg/d, 0.1 μg/d, or 0.2 μg/d of 1α-OH-D2; a control group received vehicle (coconut oil). The drug was administered by oral gavage 5 times a week for 5 weeks. The animals were then euthanized and their eyes were enucleated and processed histologically. Three serial sections from each eye were examined microscopically and the mean tumor area measured using Optimus software version 6.5 (Media Cybernetics LP, Silver Spring, Md). Toxic adverse effects were assessed on the basis of mortality, weight loss, and serum calcium levels. Results: The mean tumor size in the 0.1-μg/d and 0.2-μg/d dose groups was smaller than in the controls (Pα.001). No significant difference was seen between the 0.05-μg/d dose group and the control group (P=.64). Survival for the 0.1-μg/d and 0.2-μg/d dose groups was lower than for the controls (95% in the controls vs 85.7% and 73.7%, respectively; P<.01). Conclusion: In the Tyr-Tag transgenic mouse, 1α-OH-D2 inhibits pigmented ocular tumor growth at moderate drug levels with relatively low mortality. Clinical Relevance: Vitamin D analogues merit further preclinical study in the treatment of ocular melanoma. [ABSTRACT FROM AUTHOR]

In all fields of medicine, many investigators choose to present their research at scientific meetings before publication. In ophthalmology, a variety of organizations provide venues for such presentations, for example, at the annual meetings of the Association for Research in Vision and Ophthalmology or the American Academy of Ophthalmology. Presentations at scientific meetings provide an important venue for researchers to share their methods, results, and conclusions with some of their peers. Valuable feedback may result in the adoption of different methods, analysis of additional results, or restructuring of conclusions. The end result may be that the scientific community benefits as the work is refined and improved before publication. [ABSTRACT FROM AUTHOR]

The article presents names of reviewers who have assisted the editorial Board, authors, and readers of the journal "Archives of Opthalmology", in various publications of the year 2003. Some names included in the list are: Gary Abrams, Eduardo Alfonso, Jack Antel, Alfonso Alton, David Apple, Carl Awh, Dimitri Azar, Roy Beck, Michael W. Belin, Jurij Bilyk, Curtis Brandt, Anthony J. Brown, Jane Edmond, Traci Clemens, Kay Dickersin, Robert Folberg, Arnd Gandorfer, Roberta Gausas, Julia A. Haller, Tim Johnson, Rohit Verma.

Background: Although calcitriol (1,25-dihydroxycholecalciferol) and vitamin D[sub 2] inhibit retinoblastoma growth in the athymic (nude) mouse xenograft (Y-79 cell line) model of retinoblastoma, they can cause severe toxicity. Objective: To examine the toxicity of and dose-dependent response for the inhibition of tumor growth for 1α-hydroxyvitamin D[sub 2] (1α-OH-D[sub 2]), an analogue with reduced systemic toxicity, in the athymic Y-79 mouse model. Methods: Mice were randomized into treatment and control groups for 5-week toxicity and dose-response studies. Treatment was via oral gavage 5 times per week. Dose-response studies measured tumor inhibition and drug serum levels. Tumor size and body weight were measured weekly together with various criteria for toxicity. Animals were euthanized at the end of the treatment period. Tumors and kidneys were harvested, and serum was analyzed for calcium and drug levels. Results: Doses of 0.1 to 1.2 µg/d were selected on the basis of toxicity studies for the dose-response trial. Tumor weight and volume in the 0.2-µg and 0.3-µg doses were significantly lower than in controls. Mortality rates and kidney calcification in mice treated with doses of 0.1 to 0.3 µg were lower than those observed in studies of calcitriol and vitamin D[sub 2]. Conclusion: A vitamin D analogue, 1α-OH-D[sub 2], inhibits tumor growth in this xenograft model of retinoblastoma with less toxicity than calcitriol and vitamin D[sub 2]. [ABSTRACT FROM AUTHOR]

Background: The tumor suppressor gene p53 is expressed without apoptosis in the limbal basal stem cells of all pterygia and limbal tumors and most pingueculae from which these growths seem to originate. Oncogenic human papillomaviruses (HPVs) have been found in pterygia and limbal tumors, and HPV and p53 overexpression commonly coexist in oropharyngeal and penile carcinomas. Objective: To search for HPV DNA as a cofactor in the development of pingueculae, pterygia, and limbal tumors. Methods: We examined specimens—1 of pinguecula, 13 of pterygia (7 primary, 1 recurrent, 1 with dysplasia, and 4 primary not tested for p53), and 10 of limbal tumors (2 with actinic keratosis dysplasia, 1 with conjunctival intraepithelial neoplasia, 3 with carcinoma in situ, and 4 with squamous cell carcinoma)—expressing p53. Specimens were tested for the presence of HPV DNA by the polymerase chain reaction using degenerate consensus primers for the highly conserved portion of the L1 region that encodes a capsid protein of the virus. This assay has a wide spectrum with capability of detecting essentially all known HPV types. Nested polymerase chain reaction was performed on all specimens. Primers of the cystic fibrosis gene were used to confirm the presence of genomic DNA and to rule out inhibitors. Purified HPV DNA type 11 was the positive control, and HPV-negative genomic DNA was the negative control. Results: Using consensus primers for the highly conserved portion of the L1 region, all specimens of pingueculae, pterygia, and limbal tumors studied were negative for HPV DNA by nested polymerase chain reaction. Conclusions: Human papillomavirus DNA is not required as a cofactor in the development of pterygia and limbal tumors. These data support the theory that increased p53 expression in the limbal epithelia of pingueculae, pterygia, and limbal tumors indicates the probable existence of p53 mutations in these cells as an early event in their development, which is... [ABSTRACT FROM AUTHOR]

Objective: To determine if quality of life differs between patients with choroidal melanoma treated with enucleation and those treated with radiation therapy. Materials and Methods: Patients treated for choroidal melanoma at 5 Midwest centers were asked to participate. There were 65 participants treated with enucleation and 82 treated with radiation therapy. Quality of life was assessed using the Medical Outcome Study Short Form 36 and the National Eye Institute Visual Function Questionnaire and by the Time-Tradeoff interview method. Results: The average length of follow-up was 4.9 years for the group treated with radiation therapy and 6.3 years for the group treated with enucleation (P = .05). After adjusting for age, sex, years of follow-up, and the number of chronic conditions, there were few differences in any of the quality-of-life measures by treatment status. Participants in the group treated with radiation therapy were more likely to have higher (better) scores on the Vitality and Mental Component subscales of the Medical Outcome Study Short Form 36 than participants treated with enucleation. There were no differences on the National Eye Institute Visual Function Questionnaire or the TimeTradeoff measures of quality of life. Conclusion: Choice of treatment for choroidal melanoma does not seem to be associated with large differences in quality of life in long-term follow-up. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate the in vivo efficacy and toxicity of the 1,25-dihydroxy-16-ene-23-yne-vitamin D[sub 3] (16,23-D[sub 3]) analogue in athymic nude mice injected with Y-79 human retinoblastoma cells and to compare the efficacy and toxicity of this compound with those of 1,25dihydroxycholecalciferol (D[sub 3], calcitriol). Methods: Thirty athymic nude mice (4-6 weeks old) were injected subcutaneously with 1 x 10[sup 7] Y-79 human retinoblastoma cells suspended in a 1:1 mixture of Iscove culture medium supplemented with 20% fetal bovine serum and basement membrane matrix suspension. Five days after tumor injection, the mice were randomized to 3 groups of 10 mice each. The first group served as a control group and received intraperitoneal injections of 0.25 mL of mineral oil (vehicle) 5 times a week. The second group received intraperitoneal injections of 0.05 µg of calcitriol in 0.25 mL of mineral oil intraperitoneally 5 times a week. The third group received intraperitoneal injections of 0.5 µg of 16,23-D[sub 3] in 0.25 mL of mineral oil 5 times a week. Injections were continued for 5 weeks, during which tumor size and mouse weight were individually measured. Toxicity was assessed by clinical measures such as lethargy, weight loss, and death. The mice were then killed and the size, volume, and weight of each tumor were determined. Also, in representative animals in each group, kidneys were evaluated for calcification and serum calcium concentration was measured. Results: All experimental and control animals developed tumors subcutaneously. The 16,23-D[sub 3]-treated mice had significantly smaller average tumor size (1.55 cm[sup 3]) than the control mice (3.45 cm[sup 3]) (P = .02), less gain in average body weight from the beginning of treatment (2.4 g vs 5.5 g) (P = .06), and a 40% mortality. The calcitrioltreated mice did not have significantly smaller average tumor size (1.26 cm[sup 3]) than the 16,23-D[sub 3]-treated mice (P = .35), had... [ABSTRACT FROM AUTHOR]

Objectives: To present and discuss 2 patients with acquired peripapillary pigmented lesions. Methods: We reviewed the patients' clinical records and histopathologic findings. Results: The first patient was diagnosed with a pigmented papillary lesion that was followed up for 38 years. The second patient was a child with neurofibromatosis type 1 who developed a pigmented peripapillary lesion following excision of an optic nerve glioma. Histologic findings in both cases demonstrated hyperplasia of the retinal pigment epithelium with associated findings. Conclusions: The lesions presented an idiopathic reactive hyperplasia of the retinal pigment epithelium. The clinical and histopathologic findings resemble findings reported with the combined hamartoma. We suggest that such lesions are reactive in nature, rather than hamartomatous. [ABSTRACT FROM AUTHOR]

Lists the reviewers for the 1998 issue of the periodical 'Archives of Ophthalmology.' T. Aaberg; M. Behrens; C. Burgoyne; T. Cowden; H. Edelhauser; R. Gausas; R. Hemady; J. Jumblan; S. Lambert; K. Joos; E. Helveston; J.D. Gass; C. Becker; D. Budenz; M.F. Cotch; R. Eagle.