Photodynamic therapy for corneal neovascularisation and lipid degeneration.
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Adult↗
Biomedical subjects
D M Marcus
Publications and source records attributed to D M Marcus.
Radiotherapy for recurrent choroidal neovascularisation complicating age related macular degeneration.
AIMS: To report the safety and visual outcome data of external beam irradiation for recurrent choroidal neovascularisation complicating age related macular degeneration. METHODS: Eighteen consecutive eyes received external beam irradiation with seven fractions of 2 Gy (total dose 14 Gy). The next 16 consecutive eyes received external beam irradiation with five fractions of 3 Gy (total dose 15 Gy). Main outcome measure was change in visual acuity. Secondary outcome variables were contrast sensitivity and fundus photographic/fluorescein angiographic progression. RESULTS: The 3 Gy fraction group lost fewer lines of distance visual acuity at the three and six month follow up. At one year follow up, this difference was not maintained with 2 Gy fraction and 3 Gy fraction eyes. At one year follow up a decrease in visual acuity of three or more lines (moderate visual loss) occurred in 58% of 2 Gy and 42% of 3 Gy fraction eyes (p<0.36). At one year follow up a decrease in visual acuity of six or more lines (severe visual loss) occurred in 41% of 2 Gy eyes and 17% of 3 Gy eyes (p<0.23). At three months follow up, 3 Gy eyes were less likely (0%) than 2 Gy eyes (47%) to show moderate visual loss (p<0.003). However, Kaplan Meier curves estimate a significantly lower rate of severe visual loss in the 3 Gy group (p = 0.02). There were no significant differences in contrast sensitivity loss or fluorescein angiographic stabilisation rates. No evidence of radiation toxicity was observed. CONCLUSION: Our results are consistent with trends for a palliative benefit with higher fraction sizes and doses. The radiobiologic differences between low and high fraction size groups in this study are modest and correlate with the modest and short term difference in visual outcomes. These trends support further investigation of radiotherapy using fraction sizes of 4 Gy or higher.
Aged↗
Review of alternative therapies for treatment of menopausal symptoms.
Many women use alternative therapies to treat hot flushes and other menopausal symptoms. The purpose of this review is to summarize current information on the efficacy and safety of phytoestrogens and the herbal medicine black cohosh. A preponderance of evidence indicates that phytoestrogens are ineffective in treating hot flushes. Trials of black cohosh, many of which are small, of limited duration and of poor methodological quality, provide conflicting results, and at present it is unclear whether black cohosh is more effective than placebo. Although phytoestrogens and black cohosh appear to be safe when used for short periods of time, much larger and longer studies are needed to detect infrequent but potentially serious adverse events. Women who do not wish to take hormone therapy to treat menopausal symptoms should be encouraged to consider using selective serotonin reuptake inhibitors and other conventional therapeutic options.
Cimicifuga↗
In memoriam. Elvin Abraham Kabat, September 1, 1914-June 16, 2000.
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Allergy and Immunology↗
Purtscher retinopathy as the initial sign of thrombotic thrombocytopenic purpura/hemolytic uremic syndrome.
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Fatal Outcome↗
Is there a role for ginger in the treatment of osteoarthritis?
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Complementary Therapies↗
How should alternative medicine be taught to medical students and physicians?
Advocates of alternative medicine are critical of current medical curricula, and have proposed fundamental changes, including the introduction of "integrative medicine" programs to teach alternative medicine. Medical educators have not replied to these criticisms, and have not developed basic curricula in alternative medicine. The author analyzes the alleged deficiencies in medical education, which are based on misrepresentations of medicine and medical training. (For example, critics state that physicians ignore mind-body interactions; in response, several examples are given to show that training physicians to consider the whole person and to identify and address emotional and social problems-the biopsycho-social model-are central tenets of medical education.) The author also examines fundamental differences between traditional and alternative medicine (e.g., their different attitudes toward the importance of evidence; the vitalistic versus the biomedical models of health and disease) that are central to the issue of how alternative medicine should be taught. He concludes that physicians need additional education in order to provide guidance to patients, but teaching about alternative medicine should be evidence-based, not merely the transmission of unproven practices.
Complementary Therapies↗
Traumatic giant macular hole.
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Epiretinal Membrane↗
Sleep disorders: a risk factor for pseudotumor cerebri?
OBJECTIVE: To determine whether sleep-related breathing disorders are common in patients with idiopathic intracranial hypertension. MATERIALS AND METHODS: Medical records of 53 patients with idiopathic intracranial hypertension from a tertiary center neuroophthalmology practice were reviewed. Thirty-seven patients were identified who had a history of snoring, difficulty sleeping, or daytime somnolence. The data from polysomnograms were tabulated to determine the frequency of apneas, hypopneas, and arousals. RESULTS: Fourteen of 37 patients with idiopathic intracranial hypertension and symptoms of sleep disturbance underwent polysomnography. There were two men and 12 women varying in age from 24 to 58 years (mean, 39.4 +/- 11.9). These patients were obese with body mass indexes varying from 33.0 to 63.2 (mean, 46.0 +/- 9.5). A diagnosis of sleep apnea was made in six and upper airway resistance syndrome in seven patients. CONCLUSIONS: Sleep-related breathing problems were common in our patients with idiopathic intracranial hypertension. Obesity was common in these patients and may be playing a causative role in sleep apnea and idiopathic intracranial hypertension. It is suggested that idiopathic intracranial hypertension patients who have symptoms of sleep disturbance should be further evaluated for the presence of sleep-related breathing problems.
Adult↗
Sleep disorders: a risk factor for normal-tension glaucoma?
PURPOSE: To determine the prevalence of sleep-related symptoms and sleep-related breathing disorders by polysomnography in patients with normal-tension glaucoma (NTG). PATIENTS AND METHODS: This comparative case series included 23 patients with NTG, 14 NTG suspects, and 30 comparison patients without NTG. A sleep history was obtained and determined to be positive or negative. Polysomnography was offered for patients with a positive sleep history. Prevalence of a positive sleep history and prevalence of sleep disorders were the main outcome measures. RESULTS: The NTG, NTG suspect, and comparison groups did not differ with respect to age, body mass index, systemic disease, gender, or race. Thirteen (57%) of 23 patients with NTG, 6 (43%) of 14 NTG suspects, and 1 (3%) of 30 comparison patients had a positive sleep history (P = 0.001). Nine of 13 patients with NTG and four of six NTG suspects with a positive sleep history chose to undergo polysomnography. Seven (78%) of nine patients with NTG and all four NTG suspects undergoing polysomnography were diagnosed with a sleep disorder. Five patients with NTG had sleep apnea and two had sleep hypopnea. Two NTG suspects had sleep apnea; one had sleep hypopnea; and one had upper airway resistance syndrome. The one comparison patient with a positive sleep history had upper airway resistance syndrome by polysomnography. CONCLUSIONS: Sleep-disturbed breathing may be a risk factor for NTG. Although we do not provide evidence for a cause-and-effect relationship, various physiologic factors produced by sleep-disturbed breathing may play a significant role in the pathogenesis of this optic neuropathy. We recommend obtaining a sleep history from patients with NTG and performing polysomnography in those patients with sleep disturbance symptoms.
Adult↗
Reduced severity of oxygen-induced retinopathy in eNOS-deficient mice.
PURPOSE: Exposure of premature human infants to hyperoxia results in the obliteration of developing retina capillaries, leading to a vision-threatening retinopathy termed retinopathy of prematurity (ROP). The authors hypothesized that this process may be mediated in part by endothelial nitric oxide (NO)-derived oxidants such as peroxynitrite and tested this hypothesis in a mouse model of ROP. METHODS: Normal mice, mice treated with the nitric oxide synthase (NOS) inhibitor N:(G)-nitro-L-arginine (L-NNA), and knockout mice carrying a homozygous targeted disruption of the gene for endothelial NOS (eNOS) were studied in an experimental model of ROP. Retinas were compared for extent of capillary obliteration in hyperoxia, vascular endothelial growth factor (VEGF) expression, nitrotyrosine formation, and vitreous neovascularization. RESULTS: Oxygen-induced retinal vaso-obliteration was significantly reduced by L-NNA treatment (43% decrease from controls). The eNOS-deficient mice showed a similar reduction in vaso-obliteration (46% decrease from controls), and vitreous neovascularization was also substantially reduced (threefold decrease). Retinal nitrotyrosine formation, a measure of in situ peroxynitrite modification of proteins, was significantly elevated in normal mice during hyperoxia, in a spatial and temporal pattern consistent with a role in oxygen-induced vaso-obliteration. This was not seen in eNOS-deficient mice. VEGF expression was similar in both groups of mice, although suppression in hyperoxia was slightly blunted in eNOS-deficient mice. CONCLUSIONS: These data suggest a role for NO and peroxynitrite in the pathogenesis of ROP. Therapies aimed at modulation of eNOS activity may have therapeutic potential for preventing ROP.
Animals↗
External beam irradiation of subfoveal choroidal neovascularization complicating age-related macular degeneration: one-year results of a prospective, double-masked, randomized clinical trial.
OBJECTIVES: To determine the effects of low-dose external beam irradiation compared with observation on the visual function of eyes with subfoveal choroidal neovascularization (CNV) complicating age-related macular degeneration (ARMD). DESIGN: Prospective, double-masked, randomized clinical trial. Patients randomized to the radiation group received external beam irradiation at a dose of 14 Gy in 7 fractions of 2 Gy. Patients randomized to the observation group received sham radiation. SETTING: Tertiary care retinal referral practice. PATIENTS: Individuals with classic, mixed, or occult subfoveal CNV secondary to ARMD. MAIN OUTCOME MEASURES: Change in visual acuity from baseline to specified time periods. Secondary outcome variables were contrast sensitivity and fundus photographic/fluorescein angiographic progression. RESULTS: Forty-two eyes were randomized to observation; 41 eyes, to radiation. Baseline characteristics and demographics did not differ between groups. The median distance visual acuity (DVA) in radiation-treated eyes decreased from 20/80 at baseline to 20/320 (mean loss rate, 4.14 lines) at 1-year follow-up. The median DVA in observation group eyes decreased from 20/125 at baseline to 20/250 (mean loss rate, 3.39 lines) at 1-year follow-up. There were no statistically significant differences in changes in DVA, contrast sensitivity, or fluorescein angiographic progression from baseline between groups at any follow-up period. CONCLUSIONS: At 1-year follow-up, low-dose external beam irradiation at 14 Gy in 7 fractions of 2 Gy is neither beneficial nor harmful for subfoveal CNV complicating ARMD.
Aged↗
Ultrastructural and ERG findings in mice with adenomatous polyposis coli gene disruption.
PURPOSE: In order to continue the previous morphological studies of eyes from mice with adenomatous polyposis coli (APC) gene mutation at codon 1638, we determined the ultrastructural and electrophysiologic characteristics of these eyes. METHODS: Thirty-eight eyes from 20 mice heterozygous for APC gene mutation and 22 eyes from 11 wild-type mice were examined by light microscopy. Six APC-modified eyes without light microscopic abnormalities, four APC-modified eyes with focal light microscopic abnormalities, and four wild-type eyes were examined by electron microscopy. Electroretinograms were recorded from four APC-modified and three wild-type mice. RESULTS: Four of 38 APC-modified eyes demonstrated ultrastructural evidence of focal RPE cells with increased melanosome production and atrophy. Other areas of the RPE in these four eyes demonstrated no ultrastructural abnormalities. Three APC-modified eyes demonstrated electron and light microscopic evidence of RPE hyperplasia. Electron microscopic examination of APC-modified eyes without light microscopic evidence of abnormalities demonstrated no ultrastructural differences from age-matched controls. Electroretinography demonstrated no differences in the b-wave or c-wave amplitudes between APC-modified and wild-type mice. CONCLUSIONS: While light microscopic RPE alterations are observed in these APC-modified mice, the absence of a generalized, ultrastructural murine RPE defect is in contradistinction to observations in electron microscopic investigations of humans with colonic polyposis, pigmented ocular fundus lesions, and APC gene mutations between codons 463 and 1444. Our results in mice with APC mutation at codon 1638, however, are consistent with a previously identified association between the expression of pigmented ocular fundus lesions and region-specific mutation in the human APC gene. The APC protein may possess a physiologic function for both retinal and RPE development.
Adenomatous Polyposis Coli↗
Structure-function studies of an anti-asialo GM1 antibody obtained from a phage display library.
Although gangliosides elicit human autoantibodies, they are extremely weak immunogens in mice. We obtained a monoclonal antibody Fab fragment (clone 10) that is specific for asialo GM1 (GA1), from a phage display library. The Vkappa domain of clone 10 could be replaced by two different Vkappa domains without changing the specificity of the antibody. Mutagenesis of the third hypervariable regions of the heavy and light chains of clone 10 yielded three mutants that exhibited a 3 to 4 times increase in avidity for GA1. A molecular model of clone 10 indicated that the putative antigen-binding site contained a shallow surface pocket. These data illustrate the use of recombinant DNA techniques to obtain anti-ganglioside antibodies, and to explore the molecular basis of their antigen-binding activity.
Amino Acid Sequence↗
Treatment outcome in fellow eyes after laser photocoagulation for retinopathy of prematurity.
PURPOSE: To determine the concordance in structural outcome between fellow eyes in patients undergoing diode laser peripheral retinal photocoagulation for threshold retinopathy of prematurity. METHODS: Records from 103 patients undergoing bilateral diode laser peripheral retinal photocoagulation for retinopathy of prematurity at three academic medical centers were reviewed. Information regarding infant gestational ages, birth weights, characteristics of retinopathy of prematurity, laser treatment variables, complications, and structural outcomes were obtained. The data were analyzed to determine the rate of successful structural outcomes among all eyes as well as the interocular outcome concordance. RESULTS: A successful structural outcome was observed in 182 (88%) of the 206 eyes. Eighty-eight patients (85.4%) had bilateral favorable outcomes. Nine patients (8.7%) had bilateral unfavorable outcomes, and six patients (5.8%) had one favorable and one unfavorable eye. The outcome was concordant between fellow eyes in 94.2% of patients. This rate was higher than predicted if fellow-eye outcomes were truly independent (P < .00001) and did not depend on study center, laser settings, or location of the retinopathy of prematurity. Serious complications related to treatment were uncommon. CONCLUSIONS: Diode laser peripheral retinal photocoagulation is a safe and effective procedure for treating threshold retinopathy of prematurity. The concordance of structural outcomes between fellow eyes is higher than expected by chance and suggests that patient-specific factors play a key role in treatment response.
Birth Weight↗
Discordant retinoblastoma in monozygotic twins.
PURPOSE: We report cases of discordant retinoblastoma in twins confirmed to be monozygotic by DNA analysis. METHODS: Twin A demonstrated severe, bilateral, multifocal retinoblastoma, which was recalcitrant to external beam irradiation and chemoreduction. Twin B has not demonstrated retinoblastoma. DNA analysis was performed with polymorphic microsatellite markers to confirm monozygosity. Single-stranded conformation polymorphism and Southern blot analysis of the retinoblastoma gene were performed. RESULTS: Molecular genetic analyses confirmed monozygosity but failed to disclose a retinoblastoma gene mutation in either twin. CONCLUSIONS: The extreme phenotypic discordance may best be explained by an unidentified, postzygotic retinoblastoma gene mutation in early embryonic development of the affected twin.
Blotting, Southern↗
Use of peptide ligands to analyze the fine specificity of antibodies against asialo GM1.
We recently described clone 10, a monoclonal Fab fragment that binds to asialo GM1 (GA1), and three mutated Abs derived from it that also bind GA1 and have a three to four times increase in avidity. We selected a phage display linear heptapeptide library with these four Abs, and an IgM mAb, 156, which binds to GM1 and GD1b, but not to GA1. Peptides with the same motif, KL/VWQXXX, were selected by clones 10 and the two heavy chain mutants 227 and 109. In contrast, the light chain mutant L3 58 selected an entirely different peptide motif, TFGLQSL. Moreover, a different motif, K/SWTNL/MPP, was selected by mAb 156. Although mAbs clone 10 and its mutants 109, 227 and L3 58 all bind only to GA1, differences in their fine specificity were revealed by binding to peptide ligands.
Amino Acid Sequence↗
Sham radiation in clinical trials assessing radiotherapy for exudative age-related macular degeneration.
BACKGROUND: To evaluate the effectiveness of sham radiation treatments in masking patients to their randomization group in the Radiation of Age-Related Macular Degeneration (ROARMD) Study. METHODS: Patients with choroidal neovascularization complicating age-related macular degeneration were randomized to a treatment (RAD) group that received external beam irradiation (seven treatment sessions) or to a control (SHAM) group that received sham radiation (one sham treatment session). During a telephone survey, 62 of 73 randomized patients responded to the following questions: Do you think you received radiation? Why do you feel that way? Did the vision in your study eye worsen after enrollment? RESULTS: Eighty-one percent of the RAD group and 59% of the SHAM group thought that they had received radiation. In patients who thought that their vision had stabilized or improved, 82% thought that they had received radiation. In patients who thought that their vision was worse, only 39% thought that they had received radiation. In 54% of patients, subjective perception of vision influenced their guess as to whether they received radiation. CONCLUSIONS: Subjective patient perception of visual outcome was the most influential variable for masking. Variation between radiation treatment and sham session techniques, such as equipment used and duration of treatments, played a lesser role in the masking of patients. Seven treatment days correlated with a higher number of patients who thought that they had received radiation. Although our procedures do not strictly mask the two groups, one sham radiation session was effective in keeping patients guessing their randomization group.
Aged↗