Abstracts from the North American Rhinology & Allergy Conference, February 3, 2011, Puerto Rico.

INTRODUCTION: To establish the efficacy of bepotastine besilate ophthalmic solution (bepotastine) 1.5%, a dual acting histamine H1 receptor antagonist approved for treatment of ocular itching associated with allergic conjunctivitis, compared to placebo in relieving ocular itching and redness for subjects with active allergic rhinoconjunctivitis. METHODS: A randomized, double-masked, placebo-controlled, confirmatory natural exposure study of bepotastine 1.5% and placebo was conducted during allergy season at 12 clinical sites throughout the U.S. Following a 7-day screening period, eligible subjects ≥12 years old were assigned in a 1:1 ratio to dosing OU b.i.d. either bepotastine 1.5% (n = 123) or placebo (n = 122). Subjects recorded instantaneous grades for their ocular symptoms prior to their next dose for 14 consecutive days. Clinically significant reduction in ocular sign or symptom grades between treatment groups required p ≤ 0.05 as determined by ANCOVA analysis. RESULTS: Significant clinical effectiveness with bepotastine 1.5% was demonstrated over the 2-week treatment period in comparison to placebo in the intent-to-treat population for reducing mean instantaneous grades for both ocular itching (p = 0.007) and redness (p = 0.001). Investigator rating of efficacy over the 2-week treatment period across response categories was also superior for bepotastine 1.5% compared to placebo (p = 0.024). Only one subject discontinued participation in the study due to an adverse event. CONCLUSIONS: These data support bepotastine 1.5% as an effective treatment for allergen-induced signs and symptoms in a clinical study designed to closely resemble the conditions under which patients with allergic rhinoconjunctivitis would require treatment.

A population-based nested case-control study of the costs of hip and knee replacement surgery.

BACKGROUND: Studies of total joint arthroplasty (TJA) have not evaluated the costs and outcomes in the context of expected arthritis worsening. OBJECTIVES: Using a cost-consequence approach, to examine changes in direct health care costs and arthritis severity after TJA for hip/knee arthritis compared with contemporaneous changes in matched controls. RESEARCH DESIGN: Case control study nested in a population-based prospective cohort. SUBJECTS: In a population cohort with disabling hip/knee osteoarthritis followed from 1996 to 2003, primary TJA recipients were matched with cohort nonrecipients on age, sex, region of residence, comorbidity, and inflammatory arthritis diagnosis. MEASURES: Pre- and postoperative total and arthritis-attributable direct health care costs, arthritis severity, and general health status were compared for cases and matched controls. RESULTS: Of 2109 participants with no prebaseline TJA, 185 cases received a single elective TJA during the follow-up period; of these, 183 cases and controls were successfully matched. Mean age was 71 years, 77.6% were female, 35.5% had > or =2 comorbidities, and 81.5% had > or =2 joints affected. At baseline, controls had less pain and disability and lower total and arthritis-attributable health care costs than cases. After surgery, although overall health care utilization was unchanged, cases experienced significant decreases in arthritis-attributable costs (mean decrease $278 including prescription drugs) and pain and disability (P < 0.0001 for all). Over the same time period, controls experienced a significant increase in total health care costs (mean increase $1978 including prescription drugs, P = 0.04) and no change or worsening of their arthritis status. CONCLUSION: Compared with matched controls, arthroplasty is associated with significant reductions in pain, disability, and arthritis-attributable direct costs.

The transition study: a look at youth and adults with cerebral palsy, spina bifida and acquired brain injury.

A group of 100 adults and 190 youth who have cerebral palsy (CP), spina bifida (SB), and acquired brain injuries from childhood (ABIc) participated in a multi-method study focused on the transition to adult health care. The results show that 95% of youth and 61% of adults were living with their parents; 23% of the youth and 55% of adults were employed; and 60% of youth and 42% of adults reported "excellent" or "very good" health. The lowest health scores were reported by adults with SB. These findings provide a starting point for examining health issues specific to youth and young adults with CP, SB, and ABIc.

The Community Balance and Mobility Scale--a balance measure for individuals with traumatic brain injury.

OBJECTIVE: To provide evidence for the validity and reliability of a new outcome measure of balance, the Community Balance and Mobility Scale, developed for the ambulatory individual with traumatic brain injury. DESIGN: A validity and reliability study. SETTING: Acute care, in- and outpatient rehabilitation and day hospital settings. SUBJECTS: Two convenience samples (n=36, 32) of ambulatory patients with traumatic brain injury. MAIN MEASURES: The content and construct validity, test-retest, inter- and intra-rater reliability and internal consistency of the Community Balance and Mobility Scale. RESULTS: Content validity was demonstrated by the involvement of patients with traumatic brain injury (n=7) and clinicians (n=17) in the process of item generation and by physical therapists' ratings of item relevance. Further support is the correlation of the Community Balance and Mobility Scale scores with physical therapists' global balance ratings of the patient (r=0.62). Construct validity was supported by the ability of the measure to differentiate between patients along the continuum of care and also by comparisons with maximal walking velocity (r=0.64). Patients who scored greater than or less than 50 on the balance measure demonstrated significantly different Community Integration Questionnaire scores (P=0.004). The Community Balance and Mobility Scale demonstrated intraclass correlation coefficients (ICCs) of 0.977, 0.977, 0.975 and Cronbach's alpha of 0.96 for intra-, inter-, test-retest reliability and internal consistency, respectively. CONCLUSION: The Community Balance and Mobility Scale is a valid and reliable outcome measure for the ambulatory individual with traumatic brain injury.

Rasch analysis of the Western Ontario McMaster (WOMAC) Osteoarthritis Index: results from community and arthroplasty samples.

BACKGROUND AND OBJECTIVE: This study is based on secondary analysis of Western Ontario McMaster Osteoarthritis Index (WOMAC) data from a community sample over 55 years and total hip or knee arthroplasty samples presurgery and 1-year postoperative. METHODS: The WOMAC data were evaluated by Rasch analysis. Data were considered to fit the Rasch mathematical model for the pain and physical dimensions of the WOMAC if unidimensionality was confirmed by principle component analysis of the subscale and the residuals from the Rasch analysis, infit and outfit statistics were in the range of 0.80 to 1.20; if there was no differential item functioning based on gender or hip vs. knee subjects; and, if there was stability of the item logits across the three data samples. RESULTS: A three-item pain dimension (excluding night pain and pain on standing) and a 14-item physical dimension (excluding heavy domestic duties, getting in and out of the bath and getting on and off the toilet) fit the Rasch model based on these criteria. CONCLUSION: In evaluating existing health status questionnaires using Rasch methodology, it is important to evaluate relevant patient samples and longitudinal data when the measure is intended to evaluate change in status. By these criteria, a modified WOMAC questionnaire fits the Rasch model and has interval-level scaling properties.

A phase I and pharmacokinetic study of squalamine, a novel antiangiogenic agent, in patients with advanced cancers.

PURPOSE: A Phase I study of squalamine, a novel antiangiogenic agent originally isolated from the dogfish shark Squalus acanthias, was conducted in patients with advanced cancers to: (a) determine the maximum tolerated dose (MTD), dose-limiting toxicity (DLT) and pharmacokinetics of squalamine lactate when given as a 120-h continuous i.v. infusion every two weeks; and (b) to obtain information on prolonged (>120-h) continuous i.v. infusions in patients who have tolerated 120-h infusions. EXPERIMENTAL DESIGN: A rapid dose escalation scheme was used that permitted intrapatient dose escalation. Three or more patients were treated at each dose, of which at least one patient started treatment de novo at that dose. Once DLT was encountered, the dose was decreased by one dose level, and the duration of infusion was prolonged from 10 up to 30 days in 5-day increments. RESULTS: Nineteen patients were treated at eight squalamine dose levels; the number of patients/dose level who received 120-h infusions were [expressed as dose in mg/m(2)/day (number of patients initiated de novo at that dose/total number of patients treated at that dose)]: 6 (3/3), 12 (3/6), 24 (1/5), 48 (2/6), 96 (4/10), 192 (2/6), 384 (3/8), and 538 (1/5). DLT was encountered at 384 mg/m(2)/day (1/3 de novo patients, 5/8 total patients) and 538 mg/m(2)/day (1/1 de novo patients, 4/5 total patients) and consisted of hepatotoxicity, characterized by grade 3 transaminase elevations that resolved 3-11 days after ceasing squalamine infusion. Three patients did not experience hepatotoxicity when first treated at 384 mg/m(2)/day but developed DLT at the same dose when de-escalated from 538 mg/m(2)/day. Other toxicities included grade 1-3 fatigue, grade 1-2 nausea, anorexia, and neuromuscular symptoms. The maximum duration of continuous i.v. infusion was 20 days at a dose rate of 192 mg/m(2)/day in one patient without adverse effects. Pharmacokinetic calculations revealed a linear relationship between area under the curve or Cmax and squalamine dose rate up to 384 mg/m(2)/day, with a prolonged terminal squalamine persistence in patient plasma (median t(1/2) = 18 h; range, 8-48 h). Transient tumor responses were observed in a patient with synovial cell sarcoma and a patient with breast carcinoma with cutaneous metastases. CONCLUSIONS: The best tolerated dose rate of squalamine when administered as a 120-h continuous i.v. infusion was 192 mg/m(2)/day; however, patients without prior exposure to squalamine appeared to tolerate a dose rate of 384 mg/m(2)/day without DLT. On the basis of preclinical evidence of synergy with cytotoxic agents and demonstration of human safety from this trial, additional clinical trials have been initiated with squalamine in combination with chemotherapy for patients with late stage lung cancer and ovarian cancer.

Chiropractic manipulation and stroke: a population-based case-control study.

BACKGROUND AND PURPOSE: Several reports have linked chiropractic manipulation of the neck to dissection or occlusion of the vertebral artery. However, previous studies linking such strokes to neck manipulation consist primarily of uncontrolled case series. We designed a population-based nested case-control study to test the association. METHODS: Hospitalization records were used to identify vertebrobasilar accidents (VBAs) in Ontario, Canada, during 1993-1998. Each of 582 cases was age and sex matched to 4 controls from the Ontario population with no history of stroke at the event date. Public health insurance billing records were used to document use of chiropractic services before the event date. RESULTS: Results for those aged <45 years showed VBA cases to be 5 times more likely than controls to have visited a chiropractor within 1 week of the VBA (95% CI from bootstrapping, 1.32 to 43.87). Additionally, in the younger age group, cases were 5 times as likely to have had >/=3 visits with a cervical diagnosis in the month before the case's VBA date (95% CI from bootstrapping, 1.34 to 18.57). No significant associations were found for those aged >/=45 years. CONCLUSIONS: While our analysis is consistent with a positive association in young adults, potential sources of bias are also discussed. The rarity of VBAs makes this association difficult to study despite high volumes of chiropractic treatment. Because of the popularity of spinal manipulation, high-quality research on both its risks and benefits is recommended.

Inhibition of serotonin reuptake by antidepressants and upper gastrointestinal bleeding in elderly patients: retrospective cohort study.

OBJECTIVES: To determine the association between inhibition of serotonin reuptake by antidepressants and upper gastrointestinal bleeding. DESIGN: Retrospective cohort study from population based databases. SETTING: Ontario, Canada. PARTICIPANTS: 317 824 elderly people observed for more than 130 000 person years. The patients started taking an antidepressant between 1992 and 1998 and were grouped by how much the drug inhibited serotonin reuptake. Patients were observed until they stopped the drug, had an upper gastrointestinal bleed, or died or the study ended. MAIN OUTCOME MEASURE: Admission to hospital for acute upper gastrointestinal bleeding. RESULTS: Overall, 974 bleeds were observed, with an overall bleeding rate of 7.3 per 1000 person years. After controlling for age or previous gastrointestinal bleeding, the risk of bleeding significantly increased by 10.7% and 9.8%, respectively, with increasing inhibition of serotonin reuptake. Absolute differences in bleeding between antidepressant groups were greatest for octogenarians (low inhibition of serotonin reuptake, 10.6 bleeds/1000 person years v high inhibition of serotonin reuptake, 14.7 bleeds/1000 person years; number needed to harm 244) and those with previous upper gastrointestinal bleeding (low, 28.6 bleeds/1000 person years v high, 40.3 bleeds/1000 person years; number needed to harm 85). CONCLUSIONS: After age or previous upper gastrointestinal bleeding were controlled for, antidepressants with high inhibition of serotonin reuptake increased the risk of upper gastrointestinal bleeding. These increases are clinically important for elderly patients and those with previous gastrointestinal bleeding.

Making decisions about cancer screening when the guidelines are unclear or conflicting.

OBJECTIVE: Our purpose was to determine the factors involved in the cancer screening decisions of family physicians in situations where the clinical practice guidelines are unclear or conflicting as opposed to when they are clear and uncontroversial. STUDY DESIGN: We analyzed discussions with focus groups using a constant comparative approach. POPULATION: A total of 73 family physicians in active practice participated in 10 focus groups (1 urban group and 1 rural group in each of 5 Canadian provinces). OUTCOME MEASURES: Our main outcome measures were participants' perceptions regarding cancer screening when the guidelines were unclear or conflicting. RESULTS: We propose a model of the determinants of cancer screening decision making with regard to unclear and conflicting guidelines. This model is rooted in the physician-patient relationship, and is an interactive process influenced by patient factors (anxiety, expectations, and family history) and physician factors (perception of guidelines, clinical practice experience, influence of colleagues, distinction between the screening styles of specialists and family physicians, and the amount of time and financial costs involved in performing the maneuver). CONCLUSIONS: Our model is unique, because it is embedded in the physician-patient relationship. Ultimately, a modified model could be used to design interventions to assist with the implementation of preventive services guidelines.

Cross-cultural comparisons of health status in Canada using the Health Utilities Index.

OBJECTIVE: The purpose of this study was to examine the differences in health status, as measured by the Health Utilities Index (HUI), among seven cultural groups in Canada defined by place of birth and language. DESIGN: The study analysed cross-sectional data from the National Population Health Survey conducted by Statistics Canada in 1994-95. RESULTS: Age-standardized prevalence of dysfunction, defined as HUI < 0.83, varied from 12.7% in English-speaking immigrants to 17.8% in French-speaking Canadians. Considerable differences between the groups were found in the reporting of pain, emotional function, and cognitive function. The variation in HUI scores across the cultural groups could not be explained by differences in socioeconomic status and self-reported chronic conditions. CONCLUSIONS: Although the healthy immigrant effect is probably responsible for some of the variation in health status among cultural groups in Canada, considerable differences exist within the immigrant and Canadian-born populations. Cultural factors may have a substantial effect on the reporting of pain and mental health problems. Further studies are needed to determine the cross-cultural validity of the HUI.

A spermine-coupled cholesterol metabolite from the shark with potent appetite suppressant and antidiabetic properties.

OBJECTIVE: We describe the pharmacological properties of a novel spermine-cholesterol adduct, MSI 1436 (3beta-N-1(spermine)-7alpha, 24R-dihydroxy-5alpha-cholestane 24-sulfate), which causes reversible suppression of food and fluid intake in mammals resulting in profound weight loss, not associated with other signs or symptoms of illness, and which exhibits antidiabetic properties in genetically obese mice. METHODS: Wild-type rodents and strains with genetic obesity were studied. Effects on food and fluid intake, body weight and composition were examined along with pharmacological and toxicological parameters. RESULTS: MSI-1436 induces profound inhibition of food and fluid intake in rats and mice, resulting in significant weight loss. MSI-1436 is active when introduced directly into the third ventricle of the rat, suggesting the compound acts on central targets. Pair-feeding studies suggest that MSI-1436 causes weight loss by suppressing food intake. Fluid intake is also profoundly reduced but animals remain normally hydrated and defend both water and electrolyte balance from parenteral administration. MSI-1436 is active in ob/ob, db/db, agouti and MC4 receptor knockout mice. MSI-1436 has been administered to ob/ob mice over a 4 month period via a regimen that safely controls body weight, glucose homeostasis and serum cholesterol levels. Following MSI-1436 treatment, db/db mice preferentially mobilize adipose tissue and hyperglycemia is corrected. CONCLUSION: A naturally occurring spermine metabolite of cholesterol, isolated from the dogfish shark, Squalus acanthias, has been identified that induces profound reduction in food and fluid intake in rodents in a setting where thirst is preserved and fluid and electrolyte homeostasis appears to be functioning normally. MSI-1436 probably acts on a central target involving neural circuits that lie downstream from the leptin and the MC4 receptors. Although long-term administration can be accomplished safely in mice, the utility of this compound as a potential human therapeutic awaits an analysis of its pharmacological properties in man.

Squalamine treatment of human tumors in nu/nu mice enhances platinum-based chemotherapies.

Squalamine, an antiangiogenic aminosterol, is presently undergoing Phase II clinical trials in cancer patients. To broaden our understanding of the clinical potential for squalamine, this agent was evaluated in nu/nu mouse xenograft models using the chemoresistant MV-522 human non-small cell lung carcinoma and the SD human neuroblastoma lines. Squalamine was studied alone and in combination with either cisplatin or paclitaxel plus carboplatin. Squalamine alone produced a modest MV-522 tumor growth inhibition (TGI) and yielded a TGI with cisplatin that was better than cisplatin alone. Squalamine also significantly enhanced the activity of paclitaxel/carboplatin combination therapy in the MV-522 tumor model. Squalamine similarly improved the effectiveness of cisplatin in producing TGI when screened against the SD human neuroblastoma xenograft. Xenograft tumor shrinkage was seen for the MV-522 tumor in combination treatments including squalamine, whereas no tumor shrinkage was seen when squalamine was omitted from the treatment regimen. To gain a greater understanding of the mechanism by which squalamine inhibited tumor growth in the xenograft studies, in vitro experiments were carried out with vascular endothelial growth factor-stimulated human umbilical vein endothelial cells in culture exposed to squalamine. Squalamine treatment was found to retard two cellular events necessary for angiogenesis, inducing disorganization of F-actin stress fibers and causing a concomitant reduction of detectable cell the surface molecular endothelial cadherin (VE-cadherin). We propose that the augmentation by squalamine of cytotoxicity from platinum-based therapies is attributable to interference by squalamine with the ability of stimuli to promote endothelial cell movement and cell-cell communication necessary for growth of new blood vessels in xenografts after chemotherapeutic injury to the tumor.

Determining the need for hip and knee arthroplasty: the role of clinical severity and patients' preferences.

BACKGROUND: Area variation in the use of surgical interventions such as arthroplasty is viewed as concerning and inappropriate. OBJECTIVES: To determine whether area arthroplasty rates reflect patient-related demand factors, we estimated the need for and the willingness to undergo arthroplasty in a high- and a low-use area of Ontario, Canada. RESEARCH DESIGN: Population-based mail and telephone survey. SUBJECTS: All adults aged > or =55 years in a high (n = 21,925) and low (n = 26,293) arthroplasty use area. MEASURES: We determined arthritis severity and comorbidity with questionnaires, established the presence of arthritis with examination and radiographs, and evaluated willingness to have arthroplasty with interviews. Potential arthroplasty need was defined as severe arthritis, no absolute contraindication for surgery, and evidence of arthritis on examination and radiographs. Estimates of need were then adjusted for patients' willingness to undergo arthroplasty. RESULTS: Response rates were 72.0% for questionnaires and interviews. The potential need for arthroplasty was 36.3/1,000 respondents in the high-rate area compared with 28.5/1,000 in the low-rate area (P <0.0001). Among individuals with potential need, only 14.9% in the high-rate area and 8.5% in the low-rate area were definitely willing to undergo arthroplasty (P = 0.03), yielding adjusted estimates of need of 5.4/1,000 and 2.4/1,000 in the high- and low-rate areas, respectively. CONCLUSIONS: Demonstrable need and willingness were greater in the high-rate area, suggesting these factors explain in part the observed geographic rate variations for this procedure. Among those with severe arthritis, no more than 15% were definitely willing to undergo arthroplasty, emphasizing the importance of considering both patients' preferences and surgical indications when evaluating need and appropriateness of rates for surgery.

Devolution to democratic health authorities in Saskatchewan: an interim report.

BACKGROUND: In 1995 Saskatchewan adopted a district health board structure in which two-thirds of members are elected and the rest are appointed. This study examines the opinions of board members about health care reform and devolution of authority from the province to the health districts. METHODS: All 357 members of Saskatchewan district health boards were surveyed in 1997; 275 (77%) responded. Analyses included comparisons between elected and appointed members and between members with experience as health care providers and those without such experience, as well as comparisons with hypotheses about how devolution would develop, which were advanced in a 1997 report by another group. RESULTS: Most respondents felt that devolution had resulted in increased local control and better quality of decisions. Ninety-two percent of respondents believed extensive reforms were necessary and 83% that changes made in the previous 5 years had been for the best. However, 56% agreed that there was no clear vision of the reformed system. A small majority (59%) perceived health care reform as having been designed to improve health rather than reduce spending, contrary to a previous hypothesis. Many respondents (76%) thought that boards were legally responsible for things over which they had insufficient control, and 63% perceived that they were too restricted by rules laid down by the provincial government, findings that confirm the expectation of tensions surrounding the division of authority. Respondents with current or former experience as health care providers were less likely than nonprovider respondents to believe that nonphysician health care providers support decisions made by the regional health boards (45% v. 63%, p = 0.02), a result that confirmed the contention that the role of health care providers on the boards would be a source of tension. INTERPRETATION: Members of Saskatchewan district health boards supported the general goals of health care reform and believed that changes already undertaken had been positive. There were few major differences in views between appointed and elected members and between provider and nonprovider members. However, tensions related to authority and representation will require resolution.

Factors predictive of adolescents' intentions to use birth control pills, condoms, and birth control pills in combination with condoms.

Using the Theory of Planned Behaviour (Ajzen, 1988) as a conceptual framework, 705 secondary school students were surveyed to identify their intentions to use birth control pills, condoms, and birth control pills in combination with condoms. Hierarchical multiple regression revealed that the theory explained between 23.5% and 45.8% of the variance in intentions. Variables external to the model such as past use, age, and ethnicity exhibited some independent effects. Attitudes were consistently predictive of intentions to use condoms, pills, and condoms in combination with pills for both male and female students. However, there were differences by gender in the degree to which subjective norms and perceived behavioural control predicted intentions. The findings suggest that programs should focus on: creation of positive attitudes regarding birth control pills and condoms; targeting important social influences, particularly regarding males' use of condoms; and developing strategies to increase students' control over the use of condoms.

Health-adjusted life expectancy at the local level in ontario.

Health expectancy measures are becoming a common method of combining information on mortality and health-related quality of life into one summary population health measure. However, health expectancy measures are infrequently measured at the local level, despite a shift toward health service planning to that level. Using a modified Sullivan method, we calculated health-adjusted life expectancy (HALE) for the 42 public health units in Ontario using life tables that were derived from mortality and population data for 1988-1992 and the Health Utilities Index from the 1990 Ontario Health Survey. There were large variations among health units in HALE at age 15 for both men (range: 51.3-58.2 years) and women (range: 56.6-62.9 years). Generally, rural and northern areas had the lowest HALE. Local differences in male HALE were greater than for life expectancy (7.1 versus 6.0 years). Despite a relatively large health survey (45,583 respondents, range: 729-1,746 per health unit), few HALE differences deviated significantly from the Ontario mean, raising concerns about the feasibility of estimating local health expectancy measures with adequate precision. Nevertheless, the wider local differences and different geographic distribution of local HALE compared with mortality measures, along with the additional benefit of being able to model the complex interaction of mortality and morbidity, suggest that HALE may be a useful population health measure.

A short formal synthesis of squalamine from a microbial metabolite.

A short formal synthesis of squalamine is described, utilizing the biotransformation product 2, which is available in one step from commercially available 3-keto-23,24-bisnorchol-4-en-22-ol (1). Regioselective C-22 oxidation and C-24 sulfation of the corresponding alcohols in the presence of a free C-7 alcohol make for an efficient preparation of squalamine intermediate 11.

Squalamine improves retinal neovascularization.

PURPOSE: Modalities for inhibiting neovascularization may be one avenue to the development of effective therapies for retinopathy. The effect of squalamine, an antiangiogenic amino sterol, on oxygen-induced retinopathy (OIR) was assessed in a mouse model. METHODS: OIR was induced in C57BL6 mice by a 5-day exposure to 75% oxygen from postnatal day (P)7 through P12. Squalamine (25 mg/kg, subcutaneous)treated animals received either daily doses for five days from P12 to P16 or one dose just after removal from oxygen on P12. Each set of animals was killed at P17 to P21. Retinopathy was assessed with a retinopathy scoring system evaluation of retinal wholemounts and by quantification of neovascular nuclei on retinal sections. RESULTS: Animals receiving 5 days of squalamine after a 5-day exposure to oxygen had total retinopathy scores (expressed as median score with 25th and 75th quartiles in parentheses) of 4(3, 5) versus oxygen-only-reared animals with scores of 8(7, 9; P < 0.001). Animals reared in room air and animals exposed to squalamine only had similar retinopathy scores: 1(1, 2) and 1(0, 2). Oxygen-reared animals receiving single-dose squalamine also showed improvement, with a median retinopathy score of 4(4, 6.75) versus oxygen-only-reared animals with median retinopathy score of 9(7, 10; P < 0.001). There was a decreased number of neovascular nuclei extending beyond the inner limiting membrane on retinal sections in animals treated with 5 days (P < 0.01) and 1 day (P < 0.001) of squalamine. CONCLUSIONS: Squalamine significantly improved retinopathy and may be a novel agent for effective treatment of ocular neovascularization.