Volume 3, Number 51
Monday, December 22, 2003



In this issue: (click heading to view article)
Effects of Smoking on Choroidal Blood Flow Regulation
Postnatal Serum IGF-I Deficiency Associated With ROP, Other Premature Birth Complications
Dyslipidemia, Hyperglycemia and Inflammatory Adhesion Molecules in hRVE Cells
Retinal Vascular Abnormalities in Type I Diabetics
Briefly





Review of Ophthalmology Online will not be published next Monday, December 29. We will return on January 5, 2004. A safe, healthy and happy holiday to all our readers, from the staff of Review.

Stephen E. Pascucci, MD, Medical Editor
Gretchyn Bailey, Editor Therese DeAngelis, Associate Editor
Joe Morris, Art/Production Director Layla Voll, Circulation Director











Effects of Smoking on Choroidal Blood Flow Regulation

Little is known about potential effects of smoking on ocular blood flow regulation. This study by the Department of Clinical Pharmacology, Vienna University, Austria, hypothesizes that in chronic smokers, choroidal blood flow changes are altered during an increase in ocular perfusion pressure induced by isometric exercise.

In an observer-masked, two-cohort study, 24 healthy male volunteers (12 smokers and 12 nonsmokers) were tested for the difference in choroidal blood flow regulation between the smokers and nonsmokers during isometric exercise over six minutes. Researchers assessed choroidal blood flow with laser Doppler flow; they calculated ocular perfusion pressure (OPP) from mean arterial pressure and intraocular pressure (IOP).

Six minutes of isometric exercise induced a significant increase in mean arterial pressure, pulse rate, OPP and choroidal blood flow in smokers and nonsmokers. The increase in choroidal blood flow was significantly higher in the smoking group than in nonsmokers, whereas a comparable increase in mean arterial pressure, pulse rate and OPP occurred in smokers and nonsmokers. IOP remained unchanged during isometric exercise in both groups. Moreover, in smokers, choroidal blood flow started to increase at OPPs more than 49 percent above baseline, whereas choroidal blood flow in nonsmokers remained stable until an increase in OPP of 74 percent over baseline. This difference between the two groups was significant.

Authors of the study believe that the data shows abnormal choroidal blood flow regulation in chronic smokers compared with age-matched nonsmoking subjects during isometric exercise. However, the pathways responsible for this abnormal blood flow response remain to be elucidated.

SOURCES: Wimpissinger B, Resch H, Berisha F, et al. Effects of isometric exercise on subfoveal choroidal blood flow in smokers and nonsmokers. Invest Ophthalmol Vis Sci 2003;44(11):4859-63.		 Table of Contents











Postnatal Serum IGF-I Deficiency Associated With ROP, Other Premature Birth Complications

Insulin-like growth factor I (IGF-I) is necessary for normal development of retinal blood vessels in mice and humans. Because retinopathy of prematurity (ROP) is initiated by abnormal postnatal retinal development, Sweden"s Goteborg Pediatric Growth Research Center, Institute of the Health of Women and Children researched the hypothesis that prolonged low IGF-I in premature infants might be a risk factor for ROP.

Researchers at the center conducted a prospective, longitudinal study measuring serum IGF-I concentrations weekly in 84 premature infants from birth (postmenstrual ages 24 to 32 weeks) until discharge from the hospital. Infants were evaluated for ROP and other morbidity of prematurity: bronchopulmonary dysplasia (BPD), intraventricular hemorrhage (IVH) and necrotizing enterocolitis (NEC).

Results showed that low serum IGF-I values correlated with later development of ROP. The mean IGF-I +/- SEM level during postmenstrual ages 30 to 33 weeks was lowest with severe ROP (25 +/- 2.41 micro g/L); it was 29 +/- 1.76 micro g/L with moderate ROP and 33 +/- 1.72 micro g/L with no ROP. The duration of low IGF-I also correlated strongly with the severity of ROP. The interval from birth until serum IGF-I levels reached greater than 33 micro g/L was 23 +/- 2.6 days for no ROP, 44 +/- 4.8 days for moderate ROP, and 52 +/- 7.5 days for severe ROP. Each adjusted stepwise increase of 5 micro g/L in mean IGF-I during postmenstrual ages 30 to 33 weeks decreased the risk of proliferative ROP by 45 percent. Other complications were correlated with ROP and with low IGF-I levels. The relative risk for any morbidity--ROP, BPD, IVH or NEC--increased more than two-fold if IGF-I was less than or equal to 33 micro g/L at 33 weeks" postmenstrual age.

The authors of the study believe the results indicate that persistent low serum concentrations of IGF-I after premature birth are associated with later development of ROP and other complications of prematurity. IGF-I is at least as strong a determinant of risk for ROP as postmenstrual age at birth and birth weight.

SOURCES: Hellstrom A, Engstrom E, Hard AL, et al. Postnatal serum insulin-like growth factor I deficiency is associated with retinopathy of prematurity and other complications of premature birth. Pediatrics 2003;112(5):1016-20.		 Table of Contents











Dyslipidemia, Hyperglycemia and Inflammatory Adhesion Molecules in hRVE Cells

The initial determinants of retinal microvascular damage in diabetic retinopathy are not well understood, but are likely to be induced by hyperglycemia and/or dyslipidemia. The purpose of this study by Michigan State University and the University of Florida was to examine the effect of fatty acids and hyperglycemia on human retinal vascular endothelial (hRVE) cells, as a means of mimicking diabetic metabolic disorders.

Researchers assayed the expression of adhesion molecules in hRVE and human umbilical vein endothelial cells using Western blot analysis, and they confirmed results by leukocyte adhesion assay. They further investigated the mechanisms underlying the induction of adhesion molecules by fatty acids using cyclooxygenase (COX), lipoxygenase (LOX) and P450 monooxygenase (MOX) inhibitors.

Treatment of hRVE cells with polyunsaturated fatty acids for up to 24 hours resulted in a significant induction of intercellular adhesion molecule (ICAM)-1 and vascular cell adhesion molecule (VCAM)-1 protein levels. In contrast, treatment with high glucose (22 mM) for 24 hours did not affect cell adhesion molecule expression. Induction of cell adhesion molecule by the PUFAs correlated with enhanced leukocyte binding to hRVE cells. An inhibitor of LOX blocked the effect of the polyunsaturated fatty acid on ICAM-1 and VCAM-1, but COX or MOX inhibitors did not. In contrast to hRVE cells, the polyunsaturated fatty acid did not induce ICAM-1 or VCAM-1 in human umbilical vein endothelial cells.

Researchers believe that the data obtained in this study demonstrates that acute exposure to linoleic or arachidonic acid, but not hyperglycemia, induces inflammatory adhesion molecule expression in the presence of LOX in microvascular hRVE cells, but not in human umbilical vein endothelial cells. These results are consistent with the emerging hypothesis that recognizes early-stage diabetic retinopathy as a low-grade chronic inflammatory disease.

SOURCE: Chen W, Jump DB, Grant MB, et al. Dyslipidemia, but not hyperglycemia, induces inflammatory adhesion molecules in human retinal vascular endothelial cells. Invest Ophthalmol Vis Sci 2003;44:5016-22. 		Table of Contents










Retinal Vascular Abnormalities in Type I Diabetics

A recent study by the University of Wisconsin Medical School documented the frequency and distribution of retinal vascular characteristics and their relationships to various factors in persons with Type I diabetes.

In a population-based study, researchers studied 996 people in an 11-county area in south-central Wisconsin who were diagnosed with diabetes before age 30 and who were taking insulin. In addition to the 996 diabetic patients, 225 people without diabetes also participated in the baseline examination from 1980 to 1982.

Researchers took retinal photographs of seven standard fields and performed lightbox grading to determine arteriovenous (A/V) nicking and focal retinal arteriolar narrowing. They performed computer-assisted grading from a digitized image of Field 1 to determine central retinal arteriolar equivalent (CRAE), central retinal venular equivalent (CRVE) and the arteriole-to-venule ratio (AVR).

In multivariate analyses, retinopathy severity, mean arterial blood pressure, presence of gross proteinuria, glycosylated hemoglobin and history of cardiovascular disease were associated with CRAE. Retinopathy severity, age, mean arterial blood pressure, duration of diabetes, glycosylated hemoglobin level and body mass index were associated with CRVE. With the exception of glycosylated hemoglobin, similar factors were associated with AVR. Age and retinopathy severity were associated with focal retinal arteriolar narrowing and A/V nicking, respectively. In subjects 18 years or older, smoking was associated with CRAE, CRVE and A/V nicking, but not with AVR or focal arteriolar narrowing.

SOURCE: Klein R, Klein BEK, Moss SE, et al. Retinal vascular abnormalities in persons with Type 1 diabetes. Ophthalmol 2003;110(11):2118-25. 		Table of Contents




BRIEFLY
  • ACCUTOME LAUNCHES NEW BIOMETRY TRAINING PROGRAM. Accutome Inc., of Malvern, PA, recently introduced an Immersion Biometry training program. The company will send a service technician to your office to train your staff on how to use its AccuSonic A-Scan; the training includes hands-on "immersion training." Alternatively, Accutome will pay tuition for one staff member to attend a hands-on CME-certified course on biometry with the purchase of an AccuSonic A-Scan. For more information, call 800-979-2020 in U.S. and Canada, or go to www.accutome.com.
  • COOPERVISION ANNOUNCES NEW MULTIFOCAL LENS-FITTING CALCULATOR. CooperVision has introduced a new lens-fitting calculator called MultiTrack, which will offer eyecare practitioners a new system for guiding the fitting process for Frequency 55 Multifocal lenses. MultiTrack is a Palm handheld computer calculator that assists with the technical presbyopic lens fitting process. The calculator uses computer-generated fitting suggestions to offer a variety of variables from which practitioners can select to ensure initial fit success and decrease chair time. MultiTrack will be available January 7, 2004, via a no-charge download from the company website. Practitioners may also request a complimentary copy of CooperVision"s Right Fit CD, which includes MultiTrack, ToriTrack and clinical reference files for their Palm. For more information, go to www.coopervision.com.
  • ALLERGAN REINFORCES R&D ASSOCIATION. Allergan, Inc., is strengthening its research and development relationship with San Diego-based Discovery Partners International, Inc., a leader in drug discovery collaborations. The two companies are entering into a lead finding collaboration for multiple unique G Protein-Coupled Receptor (GPCR) and enzyme targets of significance to ophthalmology and neurology therapeutic areas. Financial terms of the collaboration were not disclosed. Discovery has thus far contributed to numerous drug discovery collaborations, aimed at promising new biological target areas for the biotech and pharmaceutical industries. For more information on Discovery Partners, Inc., to www.discoverypartners.com.

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