Low-dose radiation therapy for age-related macular degeneration

Background: The study was carried out to evaluate the effect of low-dose radiation therapy in patients with age-related macular degeneration. Methods: One hundred eyes of 78 patients (mean age 72 years) with different forms of age-related macular degeneration were treated with external beam radiotherapy between 1971 and 1989. In four fractions a total dose of 2 Gy was administered over 7 days. Radiation therapy was performed by the conventional 200-kV technique. The mean duration of follow-up period was 7 years (range 0.5 to 20 years). A control group was composed of 96 eyes from patients with AMD who received no therapy. The mean visual acuity at first presentation and the duration of follow-up was the same as in the treatment group. Results: No difference in visual acuity between the treatment and control groups could be observed. After 1, 2, 5 and 10 years the mean visual acuity was equal in the radiation group and the control group. Even in subgroup analysis regarding only the eyes with exudative forms of AMD, no effect of this treatment strategy could be demonstrated. Conclusion: Our results suggest that low-dose radiation therapy in patients with age-related macular degeneration has no beneficial effect. However, it must be considered that the dose of 2 Gy is low in comparison to doses used in recently published studies (5–24 Gy).Parts of this work were presented at the XXth Meeting of the Club Jules Gonin, Bern, 1–6 September 1996 and at the 94th Congress of the German Ophthalmological Society, Mannheim, 21–24 September 1996     

Disturbances of binocular vision in macular heterotopia]

BACKGROUND: Tractive translocation of the macula (secondary macular heterotopia) may result in disturbance of binocular vision. The report of a case shall discuss the sensorial problems of these patients. HISTORY AND SIGNS: We report of a 40-years old male who had decreased visual acuity and loss of binocular vision for several years due to episodes of uveitis with intravitreous hemorrhage and cataract formation. After bilateral vitrectomy and cataract extraction a good visual acuity was restored in both eyes. Postoperatively, the patient monocularly complained about disturbed egocentric localization (tilting of the visual environment, "past-pointing") and metamorphopsia. Binocularly he was confused by doubled vision with tilted images. Both maculae showed a tractive translocation of 15 degrees downward. Measurements of binocular alignment with the tangent screen showed an excyclotropia of 8 degrees and an exotropia of 7 degrees in all directions of gaze. Haploscopic examination with fusion images demonstrated that sensorial fusion was not possible even with perfect ocular alignment due to disturbed relative retinal localization (obligate fixation disparity). THERAPY AND OUTCOME: Initially, full time occlusion of the left eye was required. After improvement of symptoms occlusion therapy was slowly tapered. Within one year the patient had learned to suppress the image of his left eye and reported only minor residual visual disturbances even without occlusion of his left eye. CONCLUSIONS: Secondary translocation of the macula monocularly results in a disturbance of egocentric localization and in metamorphopsia. Binocularly doubled vision with tilted images and a loss of sensorial fusion are seen. With monocular vision, perceptual adapting to the aberration in egocentric localisation is possible within weeks by reallocation of the retinal meridians in the central nervous system. Binocular improvement of symptoms is limited to the learning of suppression. Improvement of binocular symptoms by adaptation of retinal correspondence does not occur.     

Management of acute submacular hemorrhage using recombinant tissue plasminogen activator and gas

· Purpose: To assess the effects of intravitreal injection of recombinant tissue plasminogen activator (rTPA) and gas on submacular hemorrhage in age-related macular degeneration (ARMD). · Methods: Eleven consecutive patients (11 eyes) with subretinal hemorrhage due to ARMD involving the fovea with elevation of the neurosensory retina were included in this study. Subretinal hemorrhage occured 12 h to 14 days before onset of therapy. Injection of rTPA through the pars plana in a dose of 50 or 100 μg was performed. Gas instillation (0.2–0.4 ml) followed rTPA injection, either immediately after injection (7 patients) or during the following day (4 patients). · Results: After intravitreal injection of rTPA, subretinal clots were totally or partially liquefied when treatment started up to 3 days after onset of bleeding. In all patients treated with 100 μg rTPA a large exudative retinal detachment of the inferior retina resulted, which reabsorbed spontaneously within 2 weeks. After reattachment of the exudative retinal detachment hyperpigmentation of the retinal pigment epithelium was noted. Temporary opacification of the vitreous was observed between the 2nd and 7th postoperative day in 5 eyes (45.5%). Postoperative visual acuity increased in 5 patients (45.5%). · Conclusion: Intravitreal application of rTPA followed by gas injection is a sufficient and convenient technique for effective removal of freshly formed submacular hemorrhage. Removal is mediated through combined enzymatic (rTPA) and mechanical (gas) effects. This technique offers a quick recovery of vision in eyes with less severe ARMD. Received: 5 January 1998 Revised version received: 25 March 1998 Accepted: 23 June 1998     

Randomized trial of radiation for age-related macular degeneration.

PURPOSE: To assess external beam radiation efficacy for subfoveal neovascularization associated with age-related macular degeneration. METHODS: All patients were evaluated in the same institution. In this prospective trial, 27 eyes (27 patients) with subfoveal neovascularization associated with age-related macular degeneration were randomized to either single fraction radiation (750 centigray) or observation. Endpoints were assessed by fluorescein angiography and Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity. Examiners were masked to patient treatment status. Parametric and nonparametric statistical analyses were performed. RESULTS: Twenty-seven patients were entered into the trial with a mean age of 76 years (range, 64 to 89) and a mean follow-up of 17 months (range, 7 to 32). The visual acuity loss was slightly less in the irradiated group, a finding of borderline significance (P < .046). There was no significant difference in fluorescein angiographic evidence of subretinal neovascular membrane change in the control group vs the irradiated group. CONCLUSIONS: External beam radiation, at this dose and fractionation, did not appear harmful. There was slightly less visual loss in irradiated eyes. No difference in fluorescein angiographic characteristics of subfoveal neovascularization size or progression in eyes with age-related macular degeneration was noted.     

Children's perceptions of parental drinking: the eye of the beholder

OBJECTIVE: Children learn about alcohol and about how to drink through modeling experience, in part. Modeling is typically studied by asking parents to describe their drinking behavior. However, children's perception of parents' drinking may differ from the way parents describe it. This study examined the degree to which children's perceptions and parents' reports agreed. METHOD: A sample of 177 grade-school children and their parents was drawn from a public school in Kentucky. Children completed questionnaires inquiring about their perceptions of the quantity, frequency and the positive and negative consequences of their parents' drinking. Their parents completed similar questionnaires describing their own drinking and its consequences. RESULTS: As hypothesized, first and second grade children's perceptions of parents' drinking were unrelated to parents' self-reports: Most of these children perceived their parents as nondrinkers even though parents reported drinking. Also as hypothesized, children's perceptions and parents' reports were significantly correlated for third through sixth grade students. However, there was a great deal of reliable, but unshared variance between these older children's perceptions and parents' reports. Children's perceptions and parents' reports were consistently quite different, even when both child and parent described the parent as a drinker. CONCLUSIONS: Studies of modeling influences on children regarding drinking should assess children's perceptions of their parents' behavior rather than parents' self-reports.     

Continuous infusion cisplatin and etoposide chemotherapy for cancer of unknown primary site (CUPS) in Taiwan, a region with a high prevalence of endemic viral infections

BACKGROUND: To evaluate the efficacy and toxicity of cisplatin/etoposide continuous infusion chemotherapy for cancer of unknown primary site in Taiwan, a region with a high prevalence of endemic viral infections. METHOD: Between April 1994 and February 1996, 20 patients with a diagnosis of CUPS were treated, including 15 males and five females, of average age 63.3 years (range 41-83 years). Continuous intravenous infusion of etoposide 80 mg/m2 and cisplatin 25 mg/m2 was given for 3 days every 3 weeks. Pretreatment tumor marker and viral serology studies were performed for baseline evaluation. Nearly two-thirds of the patients had poorly differentiated carcinoma. The average number of metastatic sites was 2.65 (range 1-4), with liver and lymph node involvement predominating. RESULTS: The overall response rate was 25% (95% CI 17.7-32.3%); 30.7% for poorly differentiated cancers and 25% for well differentiated cancers. Median survival was 4 months (range 1-12 months), 4.8 months for patients attaining partial response. Toxicity was moderate, grade 3 and 4 neutropenia occurred in 55% and grade 3 and 4 thrombocytopenia in 40%; other toxicities were mild. CA125 and CA199 were elevated in more than 50% of patients. Viral serology studies were not significantly different from those of the indigenous population. CONCLUSION: Etoposide and cisplatin combination chemotherapy has modest activity in patients with extensive CUPS and, at the schedule and dosage given, it is associated with moderate toxicity.      

Abbreviated chemotherapy with fludarabine followed by tositumomab and iodine I 131 tositumomab for untreated follicular lymphoma.

PURPOSE: To evaluate the safety and efficacy of a sequential chemotherapy plus radioimmunotherapy (RIT) regimen in previously untreated follicular non-Hodgkin's lymphoma. PATIENTS AND METHODS: Thirty-five patients received an abbreviated course (three cycles) of fludarabine followed 6 to 8 weeks later by tositumomab and iodine I 131 tositumomab. RESULTS: After fludarabine, 31 (89%) of 35 patients responded, with three (9%) of 31 patients achieving a complete response (CR). After the full regimen of fludarabine and iodine I 131 tositumomab, all 35 patients responded; 30 (86%) of 35 patients achieved CR, and five (14%) of 35 achieved partial response. After a median follow-up of 58 months, the median progression-free survival (PFS) had not been reached (95% CI, 27 months to not reached), but it will be at least 48 months. The 5-year estimated PFS rate is 60%. Baseline Follicular Lymphoma International Prognostic Index (FLIPI) was significantly associated (P = .003) with PFS. Five of six patients with more than 25% bone marrow involvement at baseline achieved adequate bone marrow cytoreduction to receive standard-dose iodine I 131 tositumomab. Ten (77%) of 13 patients with baseline bone marrow Bcl-2 positivity demonstrated molecular remissions at month 12. Toxicities were manageable and principally hematologic. Two (6%) of 35 patients developed human antimurine antibodies (HAMA) after RIT. CONCLUSION: Use of abbreviated fludarabine before iodine I 131 tositumomab can reduce bone marrow involvement, when needed, to allow the use of RIT and can suppress HAMA responses. This sequential treatment regimen is highly effective as front-line therapy for follicular lymphoma, particularly for low- or intermediate-risk FLIPI patients.