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Biomedical subjects

Timothy G Murray

Publications and source records attributed to Timothy G Murray.

At least 19 recordsLinked to original sources
PubMed2006

Macular retinoblastoma: evaluation of tumor control, local complications, and visual outcomes for eyes treated with chemotherapy and repetitive foveal laser ablation.

OBJECTIVE: To determine tumor control rates, complication rates, and visual acuity (VA) for patients with macular retinoblastoma undergoing systemic chemotherapy and foveal diode laser ablation. DESIGN: Noncomparative retrospective case series. PARTICIPANTS: All patients with retinoblastoma in the macula at the Bascom Palmer Eye Institute between 1991 and 2004 were evaluated. Patients included in the study were managed by the same clinician with a planned therapeutic strategy. METHODS: Patients with Reese-Ellsworth groups I to IV disease underwent 4 to 9 cycles of systemic chemotherapy with vincristine, etoposide, and carboplatin, and patients with group V disease underwent 6 to 10 cycles with or without cyclosporine. All tumors underwent repetitive diode laser ablation (2-24 sessions) applied to the foveal and extrafoveal portions of tumors at each visit until tumors were deemed inactive for at least 6 months. MAIN OUTCOME MEASURES: Recurrence requiring external beam radiation therapy or enucleation; VA; and complications including iris atrophy, peripheral focal lens opacity, peripheral anterior synechiae, and foveal neovascular membrane. RESULTS: Forty-four eyes of 33 patients were treated. Eyes were classified as Reese-Ellsworth group I (1 [2%]), II (6 [12%]), III (3 [7%]), IV (5 [9%]), or V (29 [67%]). Thirty-eight eyes (86%) had successful tumor control and avoided enucleation at a median follow-up of 36 months. At 3 years, tumor control rates were 100% for Reese-Ellsworth groups I to IV and 83% for group V. All eyes requiring enucleation were in Reese-Ellsworth group V. No eyes required external beam radiation. The most common complications were iris atrophy (61%) and focal lens opacity (14%). Strabismus was noted in 16% of eyes. Snellen VA measured 20/40 or better in 36% of eyes, 20/80 or better in 57%, and 20/400 or better in 86%. An increasing number of laser applications and chemotherapy cycles was not associated with decreased VA, strabismus, or development of an afferent pupillary defect but was associated with development of local complications. CONCLUSIONS: A unique approach to the application of diode laser therapy characterized by repetitive foveal treatments and aggressive chemotherapy resulted in tumor control rates that exceed those previously published. Furthermore, despite laser application directly to the fovea, 57% of patients retained 20/80 or better vision.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2006

The Wnt signaling pathway has tumor suppressor properties in retinoblastoma.

Retinoblastoma is a pediatric retinal tumor caused by mutational inactivation of the tumor suppressor pRb. Additional genetic changes, as yet unidentified, are believed to be required for tumor initiation. Mutations in the Wnt signaling pathway have been implicated in the pathogenesis of many cancers. Multiple Wnt pathway genes are expressed in the retina and the pRb and Wnt pathways interact biochemically, raising the possibility that alterations in the Wnt pathway contribute to retinoblastoma. Our studies showed that Wnt signaling activation significantly decreased the viability of retinoblastoma cell lines by inducing cell cycle arrest, which was associated with upregulated p53. Furthermore, immunolocalization of the Wnt signaling mediator beta-catenin in human and mouse retinoblastoma tissue indicated that canonical Wnt signaling is suppressed in tumors in vivo. These studies are consistent with the Wnt pathway acting as a tumor suppressor in retinoblastoma and suggest that loss of Wnt signaling is tumorigenic in the retina.

Cell Cycle↗
PubMed2006

Quality of life after iodine 125 brachytherapy vs enucleation for choroidal melanoma: 5-year results from the Collaborative Ocular Melanoma Study: COMS QOLS Report No. 3.

OBJECTIVE: To describe health- and vision-targeted quality of life following treatment with iodine 125 brachytherapy vs enucleation for choroidal melanoma in a subgroup of patients who were treated and observed prospectively as part of a large randomized clinical trial. MAIN OUTCOME MEASURES: Difficulty with driving, near vision activities, and activities using stereopsis or binocularity; anxiety; and depression. PARTICIPANTS: Two hundred nine patients who enrolled in the Collaborative Ocular Melanoma Study trial for medium-sized tumors between March 1995 and July 1998 and gave informed consent prior to randomization to participation in an ancillary study of quality of life. METHODS: Patients were interviewed by telephone by a trained interviewer from the Collaborative Ocular Melanoma Study Coordinating Center at baseline (prior to randomization), at 6 months, and on annual anniversaries of enrollment. The questionnaire battery included the Medical Outcomes Study Short Form 36, the Activities of Daily Vision Scale, the National Eye Institute Visual Function Questionnaire, and the Hospital Anxiety and Depression Scale. Additional questions concerning satisfaction with posttreatment appearance and concerns about cancer recurrence also were included in posttreatment interviews. RESULTS: There was a significant increase in both treatment groups in levels of reported difficulty for most vision-oriented activities, and in bodily and ocular pain, 6 months following treatment. Differences in visual function between treatment groups reported during follow-up were relatively small, but significant differences favoring brachytherapy-treated patients were observed for driving during the first year of follow-up and for peripheral vision during the first 2 years of follow-up. Anxiety levels in both groups decreased significantly following treatment, but patients treated with brachytherapy with symptoms of anxiety were less likely to report later resolution of symptoms than patients with symptoms of anxiety who were treated with enucleation. This study was unable to assess impact of treatment on satisfaction with appearance and concern about cancer recurrence during the first year after treatment, but no treatment-related differences were found on these measures at 2 years and later follow-up times. CONCLUSIONS: Patients treated with brachytherapy reported significantly better visual function than patients treated with enucleation with respect to driving and peripheral vision for up to 2 years following treatment. Differences between treatments in visual function diminished by 3 to 5 years posttreatment, paralleling decline in visual acuity in brachytherapy-treated eyes. Patients treated with brachytherapy were more likely to have symptoms of anxiety during follow-up than patients treated with enucleation. APPLICATION TO CLINICAL PRACTICE: Given that no significant differences in survival between enucleation and brachytherapy have been found, the differences demonstrated here for driving and anxiety will allow the individual patient and physician to make informed choices regarding treatment based on personal preferences.

Activities of Daily Living↗
PubMed2006

Early onset endophthalmitis caused by Aspergillus species following cataract surgery.

PURPOSE: To report a series of patients with early onset Aspergillus endophthalmitis following cataract surgery. DESIGN: Retrospective consecutive case series. METHODS: Medical records were reviewed of all cases of endophthalmitis caused by Aspergillus after cataract surgery treated at the authors' practices between 1992 and 2005. RESULTS: Five patients were identified. Two patients were immunocompromised (one on oral corticosteroids and one on chemotherapy for lung cancer). The mean number of days between cataract surgery and diagnosis with endophthalmitis was 29 (range, 10 to 62 days). Three eyes (60%) were enucleated despite a variety of treatments. In addition to vitrectomy and injection of antifungal agents, the other two eyes underwent surgical debridement of a localized necrotic nidus. Final visual acuity was 20/30 in one eye and 20/200 in the remaining eye. CONCLUSIONS: Aspergillus should be considered in the differential diagnosis of early onset endophthalmitis following cataract surgery. Visual outcomes are generally poor and enucleation is common in these patients.

Aged↗
PubMed2006

One-year safety and efficacy of intravitreal triamcinolone acetonide for the management of macular edema secondary to central retinal vein occlusion.

PURPOSE: To evaluate the safety and efficacy of intravitreal triamcinolone acetonide (IVTA) as treatment for macular edema associated with central retinal vein occlusion (CRVO). METHODS: A retrospective review was performed of data for 40 consecutive patients (40 eyes) with CRVO and macular edema treated with IVTA at the Bascom Palmer Eye Institute (Miami, FL). RESULTS: Median duration of symptoms before the first injection was 3 months (range, 1 day to 8 years). Median Snellen visual acuity was 20/400 at baseline (range, 20/60 to light perception; n = 40), 20/300 at 1 month (P = 0.010; n = 37), 20/300 at 3 months (P = 0.007; n = 33), 20/400 at 6 months (P = 0.726; n = 28), and 8/200 at 1 year (P = 0.569; n = 17). Vision improved by > or =3 lines in 21% of eyes at 1 month, 27% at 3 months, 14% at 6 months, and 12% at 1 year. Visual acuity was unchanged from baseline in 71% of eyes at 6 months and 1 year. By 1 year, 50% of eyes received more than one injection (mean = 1.6 injections; range 1-4 injections). Overall, intraocular pressure increased by > or =10 mmHg in 24% of eyes at 1 year. Trabeculectomy was performed on 2 of 12 eyes with preexisting open-angle glaucoma. CONCLUSION: IVTA can substantially improve vision in some patients, but most patients have stable visual acuity compared with baseline at 1 year despite repeated injections.

Adult↗
PubMed2006

Anecortave acetate as single and adjuvant therapy in the treatment of retinal tumors of LH(BETA)T(AG) mice.

PURPOSE: To evaluate the tumor control efficacy of the antiangiogenic agent anecortave acetate as single and combined therapy, in retinal tumor reduction using the LH(BETA)T(AG) mouse model of retinoblastoma. METHODS: Group A: Ten-week-old, LH(BETA)T(AG) mice received a single subconjunctival injection of anecortave acetate (1200, 600, 300, and 150 microg) delivered to right eyes only. Group B: Ten-week-old, LH(BETA)T(AG) mice received a single subconjunctival injection of anecortave acetate (600, 300, and 150 microg) delivered to right eyes only, either during a cycle of carboplatin (six subconjunctival deliveries) or after the completed cycle. Carboplatin was delivered at the subtherapeutic concentration of 62.5 microg. All animals were euthanatized at 16 weeks of age, and the eyes were examined histopathologically. RESULTS: A statistically significant reduction in tumor burden was detected after a single periocular injection of anecortave acetate. The reduction of tumor burden followed a U-shaped dose-response curve. Tumor burden was significantly decreased when anecortave acetate and carboplatin were combined. However, varying doses and delivery schedule of these agents had significant impact on the effectiveness of the combined treatment. The most effective scheme was delivering a low dose (150-300 microg) of anecortave acetate after a complete cycle of carboplatin. Histopathological evaluation showed no signs of retinal toxicity to anecortave acetate delivery alone or in combination with carboplatin. CONCLUSIONS: Anecortave acetate, as monotherapy or as adjuvant therapy, significantly controlled tumor burden in a murine model of retinoblastoma. Moreover, adjuvant therapy enabled the use of typically subtherapeutic carboplatin doses without decreasing efficacy of the therapy.

Animals↗
PubMed2006

Iontophoretic delivery of carboplatin in a murine model of retinoblastoma.

PURPOSE: To evaluate the efficacy and dose-response of transcorneoscleral Coulomb controlled iontophoresis (CCI) of carboplatin in the treatment of retinal tumors of a murine model of retinoblastoma. METHODS: Thirty 6-week-old LHBETATAG mice underwent a total of six, serial iontophoretic treatments administered two times per week using a current density of 2.57 mA/cm2 for 5 minutes. Fourteen animals received carboplatin treatments at concentrations of 1.4, 7.0, 10.0, or 14.0 mg/mL without current. Ten control mice underwent treatment with balanced saline solution. RESULTS: A dose-dependent inhibition of intraocular tumor was observed after repetitive iontophoretic treatment. At carboplatin concentrations of 7 mg/mL, 50% of the treated eyes (4/8) exhibited tumor control. No corneal toxicity was observed in eyes treated at carboplatin concentrations under 10 mg/mL. CONCLUSIONS: CCI delivery of carboplatin safely and effectively controls intraocular tumors in a dose-dependent manner in this murine model of retinoblastoma. CCI is a noninvasive, painless option for the focal delivery of carboplatin. However, further clinical and laboratory research is needed before this method of drug delivery is available for children with retinoblastoma.

Animals↗
PubMed2005

Outcomes of complex retinal detachment repair using 1000- vs 5000-centistoke silicone oil.

OBJECTIVE: To compare anatomic and visual acuity outcomes, as well as complication rates, after retinal detachment repair using 1000- vs 5000-centistoke silicone oil. METHODS: Records of all patients who underwent retinal detachment repair with silicone oil at one institution between January 1, 1995, and December 31, 2000, were reviewed. Anatomic outcomes included retinal redetachment and macula-off retinal redetachment. Visual acuity outcomes included ambulatory vision (> or =5/200) and change in visual acuity from preoperative examination. Complications included rates of secondary intraocular pressure elevation, hypotony, corneal opacification, cataract, and oil emulsification. Outcomes were assessed at 1 week, 1 month, 3 months, 6 months, and 1 year. RESULTS: The study included 82 eyes that underwent retinal detachment repair with 1000-centistoke silicone oil and 243 eyes that underwent retinal detachment repair with 5000-centistoke silicone oil. Demographic characteristics, cause of retinal detachment, and preoperative ocular characteristics were similar in the 2 groups. There was no significant difference in the rate of retinal redetachment at each of the follow-up intervals investigated. The cumulative retinal detachment rate was also similar between the 2 groups except among trauma cases, for which 1000-centistoke silicone oil was associated with a higher cumulative redetachment rate (P<.001). There was no significant difference between the groups with respect to (1) change in visual acuity from preoperatively to 6 months postoperatively and (2) the proportion of patients who achieved ambulatory vision at each of the follow-up intervals investigated. Rates of elevated intraocular pressure, hypotony, corneal abnormality, cataract, and silicone oil emulsification were similar in the 2 groups. CONCLUSIONS: Anatomic and visual acuity outcomes, as well as complication rates, were similar in both groups; retinal reattachment and ambulatory vision were achieved in most eyes regardless of oil viscosity.

Adolescent↗
PubMed2005

Retinoblastoma: animal models.

Employment of animal models in basic research has significantly advanced the understanding of fundamental processes underlying tumorigenesis in retinoblastoma, including elucidating the complex role of pRb and other related protein products in cell cycle regulation, apoptosis, DNA damage responses, and terminal differentiation. The evolution of therapy for retinoblastoma has also been facilitated through translational research using in vivo models, including xenograft and genetically engineered systems. In retinoblastoma, these models provide a valuable preclinical context for testing the efficacy and safety of conventional chemotherapy, radiotherapy, or novel agents on tumor growth, tissue invasion, and metastasis.

Animals↗
PubMed2005

Pars plana lensectomy and intraocular lens implantation in pediatric radiation-induced cataracts in retinoblastoma.

OBJECTIVE: To investigate visual outcomes, surgical complications, and tumor recurrence among children with retinoblastoma (RB) undergoing pars plana lensectomy, vitrectomy, and simultaneous intraocular lens insertion for radiation-related cataract secondary to external beam radiotherapy (EBRT). DESIGN: Retrospective, noncomparative, consecutive case series. METHODS: The medical records for all patients treated with pars plana lensectomy, vitrectomy, and posterior chamber intraocular lens implantation for radiation-induced cataract after EBRT for RB at a single institution between January 1, 1990, and December 31, 2000, were reviewed. PARTICIPANTS: The study included 16 eyes of 12 children with Reese-Ellsworth stage V RB. MAIN OUTCOME MEASURES: Visual acuity, surgical and postoperative complications, postoperative refraction, and tumor recurrence. RESULTS: The median age at diagnosis of RB was 6 months (range, 1-49 months). All patients received EBRT as primary treatment and experienced radiation-induced cataracts. The median interval from RB diagnosis to cataract surgery was 42 months (range, 28-95 months). Preoperative mean visual acuity was 20/400, with 12 of 16 eyes (75%) having macular tumor involvement. All patients underwent pars plana lensectomy, vitrectomy, and posterior chamber intraocular lens insertion. Vitreous samples were evaluated by cytopathologic examination, and no viable tumor cells were identified in any of the vitreous specimens. Postoperative complications included transient cystoid macular edema in 5 eyes (31%) and iridocyclitis in 3 eyes (19%). The mean follow-up after cataract surgery was 66 months (range, 30-94 months). Final visual acuity was 20/40 or better in 11 of 16 eyes (69%). No late intraocular recurrence, orbital tumors, or metastatic disease was noted in this study. CONCLUSIONS: Pars plana lensectomy, vitrectomy, and simultaneous intraocular lens implantation is an effective means of managing EBRT-induced cataracts in eyes with previously treated RB. There was no evidence of active tumor in eyes undergoing surgery at least 28 months after the diagnosis and commencement of therapy for RB, and no late intraocular, orbital, or metastatic tumors were detected. Visual acuity was limited by the presence of primary macular tumor pathologic features in a subset of patients, but final vision better than 20/400 may be achieved in these eyes.

Cataract↗
PubMed2005

Outcomes of iodine 125 plaque radiotherapy after initial observation of suspected small choroidal melanomas: a pilot study.

PURPOSE: To determine the visual and survival outcomes for patients undergoing plaque radiotherapy of suspected small choroidal melanomas after observation for growth in a pilot study. DESIGN: Noncomparative interventional case series. PARTICIPANTS: Forty-five patients with suspected small choroidal melanomas who were seen at the Bascom Palmer Eye Institute between 1974 and 2001 and had iodine 125 (I125) plaque radiotherapy between 1991 and 2002. METHODS: Patients with suspected small choroidal melanomas were monitored by clinical examination, photography, and echography. When the melanoma grew or developed orange pigment, patients were treated with I125 plaque radiotherapy. Outcomes included visual acuity, ocular complications, tumor dimensions, metastasis, and death. MAIN OUTCOME MEASURE: Melanoma-specific mortality. RESULTS: In our pilot study, 1 patient died from metastatic melanoma. One patient developed metastatic disease and is still alive. One patient developed marginal tumor recurrence after treatment and after enucleation was performed. Globe conservation was achieved in 97.8% of patients. In patients with tumor margins >2 mm from the optic nerve, vision was preserved with less than a doubling of the visual angle (within approximately 2 Snellen lines of preoperative acuity) in 90.6% (29/32) of patients at 1 year postoperatively, 65.6% (21/32) at 2 years, and 52.2% (12/23) in the long term (4-11 years). CONCLUSIONS: Five-year melanoma-specific mortality after I125 plaque radiotherapy of suspected small choroidal melanomas was 3.9% (95% confidence interval, 0%-11.2%). This information can be used to counsel patients with small suspected choroidal melanomas and to compare with other treatment modalities.

Adult↗
PubMed2005

Subconjunctival antibiotics in the treatment of endophthalmitis managed without vitrectomy.

PURPOSE: To determine if the treatment outcomes for endophthalmitis are influenced by subconjunctival antibiotics. METHODS: A retrospective, nonrandomized consecutive series of patients with clinically diagnosed bacterial endophthalmitis confirmed with positive cultures who presented between December 1, 1995, and February 28, 2002, was studied. Patients with cataract surgery, glaucoma filtering blebs, or trauma who presented with visual acuity of hand motions or better were included. All patients received intravitreal and topical antibiotics. Management by pars plana vitrectomy or vitreous tap and use or nonuse of subconjunctival antibiotics were at the discretion of the treating physician. RESULTS: There were 59 patients identified; 54 met the follow-up criteria. These patients were divided into two groups based on whether subconjunctival antibiotics were used (group ABX; n = 21) or not used (group noABX; n = 33). The median pretreatment visual acuity was hand motions in both groups. The median age in both groups was 74 years. Etiology, duration of symptoms, vitreous culture organisms, percentage of cases with wound complications such as leaks or vitreous incarceration, and intraocular lens type were similar in the two study groups. Intravitreal and topical antibiotics and corticosteroids used were not significantly different in the two groups, except that topical ceftazidime was used less frequently in group ABX than in group noABX (43% vs. 82%, respectively; P = 0.007). The median follow-up was 13 months in both groups (range: 3-87 months for group ABX and 3-63 months for group noABX). Final visual acuity in groups ABX and noABX was at least 20/50 (33% vs. 39%, respectively), 20/60 to 5/200 (29% vs. 39%, respectively), 4/200 to better than hand motions (0 vs. 3%, respectively), or hand motions or worse (38% vs. 18%, respectively). These differences were not significant (P = 0.37). Reinjection rates (14% vs. 15%, respectively) were also similar in groups ABX and noABX. The additional procedures rate was significantly higher in group ABX than in group noABX (P = 0.024), with cumulative rates of 33% and 3%, respectively, at the 12-month follow-up. CONCLUSIONS: These data suggest that subconjunctival antibiotics may not be necessary to treat infectious endophthalmitis managed with otherwise standard tap and injection techniques and topical antibiotics.

Administration, Topical↗
PubMed2005

Combretastatin A-4 prodrug in the treatment of a murine model of retinoblastoma.

PURPOSE: To evaluate the effect of subconjunctival injections of combretastatin A-4 phosphate (CA-4P) prodrug treatment on tumor vasculature and growth in an animal model of hereditary retinoblastoma. METHODS: Twenty-four, 12-week-old simian virus-40 T-antigen-positive mice received six subconjunctival CA-4P injections at doses of 0.5, 1.0, 1.5, and 2.0 mg delivered at 72-hour intervals to the right eye only. Six control animals received placebo treatment. All animals underwent serial ophthalmic evaluations and were euthanatized at 16 weeks of age, and eyes were obtained for histopathologic examination. Eyes were graded for presence or absence of tumor, delay of tumor growth, and intratumoral vascularity. RESULTS: The use of subconjunctivally injected CA-4P prodrug induced an extensive, dose-dependent decrease in microvessel density and led to significant tumor reduction in treated eyes compared with the placebo control (P <0.001). No evidence of corneal, lenticular, choroidal, or retinal toxicity was observed by histopathologic evaluation. CONCLUSIONS: Subconjunctival delivery of CA-4P is associated with extensive dose-dependent reduction in blood vessel count in this murine model of retinoblastoma. A combination treatment of retinoblastoma incorporating CA-4P may allow enhanced tumor reduction enabling a decrease in standard treatment doses of both chemotherapy and external beam radiotherapy.

Animals↗