In vitro efficacy of carboplatin and hyperthermia in a murine retinoblastoma cell line.

PURPOSE: To determine the cell-killing activity of varying doses of carboplatin, graded hyperthermia, and the combination of carboplatin and hyperthermia in the treatment of a transgenic murine retinoblastoma cell line. METHODS: Replicate cell wells (more than six wells per dose point) from an established transgenic murine retinoblastoma cell line (Rb-6) were exposed to a single application of hyperthermia for 15, 30, 60, and 120 minutes at temperatures of 37 degrees C (control), 40 degrees C, and 43 degrees C. Carboplatin dose response treatment was studied at doses of 2000, 1000, 500, 400, 300, 200, 100, and 50 ng per well. Combined treatment studies used these carboplatin dosages with each of the graded hyperthermia exposure temperatures at each exposure time. At 24 hours, all wells were pulsed with 3H-thymidine for 24 hours, washed three times, harvested, and counted. Raw counts (3H-thymidine) were fitted to a linear regression model to calculate the lethal dose for 50% (LD50) of cells. RESULTS: The LD50 for carboplatin exposure at 37 degrees C occurred at 542 ng. The LD50 for hyperthermia at 40 degrees C occurred at 90 minutes and at 43 degrees C it occurred at 62 minutes. Combined hyperthermia and carboplatin exposure yielded a synergistic interaction with an LD50 of 327 ng at 43 degrees C for 30 minutes. Determination of a thermal enhancement ratio yielded an enhancement range of 1.1 to 25.8. CONCLUSIONS: The synergistic cytocidal interaction of heat and carboplatin in a transgenic murine retinoblastoma cell line has been established in this study. The increased thermal enhancement ratio documents the potential utility of combined treatment applications in reducing treatment levels of single-modality therapy, potentially allowing for a decrease in treatment-related morbidity.

Nonsurgical management of macular hemorrhage secondary to retinal artery macroaneurysms.

OBJECTIVE: To report visual acuity outcomes of nonsurgical management of macular hemorrhage secondary to retinal artery macroaneurysms. METHODS: Forty-one patients at multiple centers with macular hemorrhage secondary to retinal artery macroaneurysms managed with observation alone were reviewed. Time to clearance of macular hemorrhage, visual acuity at final follow-up, and presence or absence of macular pigmentary changes after absorption of the hemorrhage were recorded for each patient. RESULTS: On initial examination, visual acuity was 20/200 or worse in all except 4 patients (3 with 20/70, 1 with 20/80). At an average follow-up of 15. 7 months, a final visual acuity of 20/40 or better was achieved in 15 eyes (37%), between 20/50 and 20/100 in 12 (29%), and 20/200 or worse in 14 (34%). Macular pigmentary abnormalities were noted after clearance of the hemorrhage in 23 (56%) of 41 cases, and these eyes generally had worse visual acuity outcomes. CONCLUSIONS: In eyes with macular hemorrhage secondary to retinal artery macroaneurysms managed with observation alone, good visual acuity outcomes can often be achieved. Poorer visual acuity outcomes are associated with macular pigmentary changes after resorption of blood. Arch Ophthalmol. 2000;118:780-785

Juxtapapillary capillary hemangiomas. Clinical features and visual acuity outcomes.

OBJECTIVE: To describe the clinical features, association with von Hippel-Lindau (VHL) disease and visual acuity outcomes of patients with a juxtapapillary capillary hemangioma. DESIGN: Retrospective observational case series. PARTICIPANTS: Seventy-two eyes of 68 patients identified with a juxtapapillary capillary hemangioma. Follow-up data of at least 6 months duration were available for 60 eyes. METHODS: A retrospective chart review of patients diagnosed with a juxtapapillary capillary hemangioma examined at four medical centers. MAIN OUTCOME MEASURES: Age at diagnosis, visual acuity (VA) at first examination and at last follow-up, tumor growth pattern and location, associated clinical features, type of treatment, association with VHL, and presence of peripheral hemangiomas were recorded for each patient. RESULTS: On initial examination, VA was >/=20/40 in 43 of 70 eyes (61%) and was >/=20/200 in 60 eyes (86%). At an average follow-up of 5.4 years (range, 0.5-19 years), VA of >/=20/40 was achieved in 21 eyes (35%) and >/=20/200 in 33 eyes (55%). Patients with VHL had poorer initial VA (48% vs. 70% with VA >/=20/40, and 74% vs. 93% with VA >/=20/200) and final VA (26% vs. 41% with VA >/=20/40, and 39% vs. 65% with VA >/=20/200) compared with patients without VHL. Patients with VHL more commonly were seen at an earlier age (average, 20 vs. 44 years, P: < 0.001), with bilateral (17% vs. 0%), and/or peripheral (39% vs. 0%) (P: < 0.001) tumors that more often had an endophytic growth pattern (63% vs. 22%, P: = 0.001) compared with patients without VHL. Patients selected for laser treatment generally had poorer initial (52% vs. 74% with VA >/=20/40, 79% vs. 96% with VA >/=20/200) and final VAs (18% vs. 56% with VA >/=20/40, 45% vs. 67% with VA >/=20/200) compared with patients not treated with laser. CONCLUSIONS: On long-term follow-up of patients with a juxtapapillary capillary hemangioma, the VA generally worsens. Patients with VHL and a juxtapapillary hemangioma more often present at a younger age, have tumors with an endophytic growth pattern, and have bilateral, multiple tumors. Treatment with laser photocoagulation results in variable VA outcomes.