Effect of Aging on Retinal Macular Microcirculation: A Blue Field Simulation Study

Purpose. Structural changes in the retina are known to occur with aging. This study was performed to investigate whether aging also affects the retinal macular microcirculation. Methods. Healthy volunteers with ages ranging from 20 to 78 years (mean ± SD, 49 ± 19 years) were included in this study. The retinal macular microcirculation was assessed with the blue field simulation technique, based on the blue field entoptic phenomenon. Subjects were asked to match the velocity and density of computer-simulated particles displayed on a screen with those of their entoptically observed leukocytes. Ten matching trials were performed, and an average leukocyte velocity and density were calculated. Results. Significant negative linear correlations were observed between velocity and age (P = 0.0001) and density and age (P = 0.009). Older subjects (50 to 78 years of age) had a significantly slower velocity (0.61 ± 0.21 mm/s) and smaller density (90 ± 43 particles per field of view) than younger subjects (0.92 ±0.12 mm/s and 135 ± 65 particles, respectively; unpaired Student's t-test, P = 0.001 and P = 0.01, respectively). Conclusions. These results suggest that, in normal subjects, retinal macular blood flow decreases with age. The 20% decrease in average velocity with age is very similar to the age-related decrease in number of cells observed in the human foveal ganglion cell layer. Invest Ophthalmol Vis Sci. 1993;34:3609-3613. X he retina undergoes several structural changes with aging

Linking complex forest fuel structure and fire behaviour at fine scales

Abstract. Improved fire management of savannas and open woodlands requires better understanding of the fundamental connection between fuel heterogeneity, variation in fire behaviour and the influence of fire variation on vegetation feedbacks. In this study, we introduce a novel approach to predicting fire behaviour at the submetre scale, including measurements of forest understorey fuels using ground-based LIDAR (light detection and ranging) coupled with infrared thermography for recording precise fire temperatures. We used ensemble classification and regression trees to examine the relationships between fuel characteristics and fire temperature dynamics. Fire behaviour was best predicted by characterising fuelbed heterogeneity and continuity across multiple plots of similar fire intensity, where impacts from plot-to-plot variation in fuel, fire and weather did not overwhelm the effects of fuels. The individual plot-level results revealed the significance of specific fuel types (e.g. bare soil, pine leaf litter) as well as the spatial configuration of fire. This was the first known study to link the importance of fuelbed continuity and the heterogeneity associated with fuel types to fire behaviour at metre to submetre scales and provides the next step in understanding the complex responses of vegetation to fire behaviour

Molecular medicine and concepts of disease: the ethical value of a conceptual analysis of emerging biomedical technologies

Although it is now generally acknowledged that new biomedical technologies often produce new definitions and sometimes even new concepts of disease, this observation is rarely used in research that anticipates potential ethical issues in emerging technologies. This article argues that it is useful to start with an analysis of implied concepts of disease when anticipating ethical issues of biomedical technologies. It shows, moreover, that it is possible to do so at an early stage, i.e. when a technology is only just emerging. The specific case analysed here is that of ‘molecular medicine’. This group of emerging technologies combines a ‘cascade model’ of disease processes with a ‘personal pattern’ model of bodily functioning. Whereas the ethical implications of the first are partly familiar from earlier—albeit controversial—forms of preventive and predictive medicine, those of the second are quite novel and potentially far-reaching

Effect of Topical Corteolol on the Normal Human Retinal Circulation

The effect of topical carteolol 1%, a beta-adrenergic blocker with intrinsic sympathomimetic activity, on the retinal circulation was investigated in 15 normal subjects using laser Doppler velocimetry and monochromatic fundus photography. In a double-masked randomized design, one eye received one drop of carteolol 1% and the fellow eye one drop of placebo. Vessel diameter, maximum erythrocyte velocity, and volumetric blood flow rate were determined in a major temporal vein of each eye just before instillation of the drops and then 120 min later. No significant changes in heart rate or mean brachial artery blood pressure were detected after treatment. Intraocular pressure decreased by 28% in the carteolol-treated eye (P < 0.0001) and by 15% in the placebo-treated eye (P < 0.001). No significant changes in vessel diameter, maximum erythrocyte velocity, and volumetric blood flow rate were observed in the carteolol-treated eyes (0.3%, 4.3%, and 3.6%, respectively) or the placebo-treated eyes (0.5%, 5.8%, and 6.7%, respectively). Invest Ophthalmol Vis Sci 33:1853-1856,1992 The influence of timolol maleate, a beta-adrenergic blocking agent, on retinal blood flow has been investigated using bidirectional laser Doppler velocimetry (BLDV) and monochromatic fundus photography (MFP). After a single instillation of timolol maleate 0.5%, a significant average increase was reported in retinal volumetric blood flow of approximately 13% in normal subjects 1 and 8% in eyes with ocular hypertension. 2 A somewhat similar effect also was observed after 2 weeks of timolol treatment. 3 Carteolol is a relatively new beta-adrenergic blocking agent with partial beta-agonist activity commonly referred to as intrinsic sympathomimetic activity (ISA). Particularly because of its ISA, we were interested in testing whether carteolol could influence retinal volumetric blood flow. Carteolol is the only approved ophthalmic beta blocker in the United States with ISA and enhancement of ocular blood flow could be therapeutically beneficial. The contribution of ISA to beta-blocker therapeutic potential has been studied extensively for cardiovascular hypertension. From th

Effect of Topical Timolol Maleate on the Ophthalmic Artery Blood Pressure

The effects of topical timolol maleate 0.5% on the ophthalmic artery diastolic (OABP d ), systolic (OABP S ) and mean blood pressure (OABP m ) were investigated in 19 healthy subjects using compression ophthalmodynamometry. In a randomized, double-blind study, one eye of each subject received one drop of timolol maleate 0.5% and the fellow eye received a drop of placebo. Measurements of OABP d and OABP S were performed just prior to instillation of the drops, and then 2 hr later. In a previous study using bidirectional laser Doppler velocimetry and monochromatic fundus photography, we have reported that topical timolol maleate 0.5% produces an average increase in retinal blood flow of 13% in the normal eye. 1 Since the average increase in perfusion pressure in these eyes was 13% and since we found a significant correlation between the individual changes in blood velocity and the changes in perfusion pressure, we concluded that the increase in blood flow is produced by the increase in perfusion pressure. In order to calculate perfusion pressure, one must determine the central retinal artery blood pressure. In this previous work, however, the central retinal artery pressure was not measured and was estimated as % of the mean brachial artery pressure minus the intraocular pressure (IOP). Measurements of the human central retinal artery blood pressure cannot be determined noninvasively at this time. A close estimation of the blood pressure in the ophthalmic artery pressure, which is only slightly higher than the central retinal artery, can be obtained, however, by compression ophthalmodynamometry. 23 To investigate whether topical timolol maleate may have an effect on the diastolic, systolic From the Scheie Eye Institute, Department of Ophthalmology, School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania. This investigation was supported in part by a grant from Chibret International, Merck Sharp and Dohme and was assisted by the use of Clinfo data management and analysis provided by a grant (RR-00040) from the NIH. Submitted for publication: January 28, 1988; accepted December 12, 1988. Reprint requests: Dr. Juan E. Grunwald, Scheie Eye Institute, 51 N. 39th Street, Philadelphia, PA 19104. and mean ophthalmic artery blood pressure (OABP d , OABP S and OABP m , respectively) we have performed the current study in which these pressures were estimated from compression ophthalmodynamometry measurements. Our results showed no significant change in OABP d , OABP S or OABP m from baseline. However, when the changes in OABP m in the timolol-treated eye were compared to the changes in the placebo-treated eyes, a statistically significant difference between eyes was detected. Although the effect of timolol maleate on aqueous humor secretion and IOP has been extensively studied in the literature, very little is known about any influence that this drug may have on the ophthalmic and retinal artery blood pressures. The ophthalmic artery and the extraocular part of the central retinal artery are known to have adrenergic innervation. Although such innervation was previously believed to be absent in the blood vessels of the mammalian retina, 45 recent reports have suggested that adrenergic nerves are present in the rabbit. Materials and Methods Nineteen healthy volunteers aged 20 to 47 years (average 28.5 ± 7.2 years, ±1 SD) with no history of systemic or intraocular disease were included in th

Effect of topical timolol on the human retinal circulation. Invest Ophthalmol Vis Sci

The effect of topical timolol maleate 0.5% on the retinal circulation was investigated in 14 normal subjects using laser Doppler velocimetry and monochromatic fundus photography. In a double masked, randomized design, one eye received two drops of timolol maleate 0.5% and the fellow eye received two drops of placebo. Vessel diameter, maximum velocity of red blood cells, and volumetric blood flow rate were determined in a major temporal vein of each eye just prior to the instillation of drops, and then 90 min later. In comparison to the baseline value, there was a significantly larger average percentage increase in maximum velocity of red blood cells and volumetric blood flow rate in the timolol-treated eyes (11.0% and 13.2%, respectively) than in the control eyes (2.2% and 1.5%, respectively, paired t-test, P < 0.05). No significant change in venous diameter was detected. No significant linear correlations were found between the percentage change in maximum velocity of red blood cells and mean brachial artery blood pressure, and between the percentage change in volumetric blood flow rate and mean brachial artery pressure in the placebo-treated eyes, whereas significant correlations were present between these quantities in the timolol-treated eyes (P < 0.01 and P < 0.05, respectively). The lack of such correlations in the control eyes is probably due to autoregulation of the retinal circulation. The presence of correlations in the timolol-treated eyes suggests that the drug may affect the capacity of the retina to autoregulate. Invest Ophthalmol Vi

Effects of oxygen and carbon dioxide on human retinal circulation

Purpose. Carbogen, a gas mixture of 95% O 2 and 5% CO 2 , is given to patients with retinal artery obstruction in an attempt to improve retinal oxygenation. The purpose of this study was to compare the effects of carbogen and 100% O 2 breathing on retinal blood flow. Methods. On two separate occasions, 12 normal, healthy volunteers breathed air and then either 100% O 2 or carbogen while laser Doppler velocimetry measurements and monochromatic fundus photographs were taken. Retinal vessel diameter, maximum velocity of red blood cells, and volumetric blood flow rate were determined in a main temporal vein. Results. Both 100% O 2 and carbogen caused significant average reductions in vessel diameter (14.1% and 10.6%, respectively), maximum red blood cell velocity (42.1% and 27.3%, respectively), and blood flow (56.4% and 42.2%, respectively). The average vasoconstriction of the large retinal veins caused by carbogen was not significantly smaller than that caused by 100% O 2 . The average reductions in maximum red blood cell velocity and blood flow caused by carbogen were significantly smaller than those caused by 100% O 2 (P < .001 and P < .01, respectively). Conclusions. In normal subjects, inhalation of carbogen leads to less reduction in blood flow than inhalation of 100% O 2 , presumably by reducing the vasoconstriction of small arterioles induced by elevated oxygen levels. Invest Ophthalmol Vis Sci 1993;34:2866-2870. Central retinal artery occlusion is a medical emergency treated by ocular massage, reduction of intraocular pressure (IOP), and inhalation therapy with gases containing high oxygen concentrations. Carbogen, a gas mixture of 95% O 2 and 5% CO 2 , is one of the gases that has been recommended for administration 10 minutes every hour during the day and every 4 hours at night. 1 " 3 Inhalation therapy is provided with the hope that hyperoxic blood from the choroid circulation may supply the ischemic inner retina and that additional oxygen may be delivered through a partially perfused retinal circulation. Flower and Patz 4 reported that hyperbaric oxygen was necessary to improve the oxygenation of the inner retina in cats and dogs with occluded August 7, 1992; accepted Novejnber 23, 1992. Proprietary interest category: N. Reprint requests: Juan E. Grunwald, M.D., Scheie Eye institute, 51 North 39th Street, Philadelphia, PA 19104. retinal circulation. One hundred percent O 2 breathing returned the electroretinographically recorded bwave (a measure of functional integrity of the Miiller cells in the inner retinal layers) to only 45% of normal amplitude. More recent studies, however, have suggested that normobaric 100% oxygen breathing can provide some oxygen to the inner retina in cats 5 ' 6 and miniature pigs 7 with occluded retinal circulation. In normal subjects, inhalation of 100% O 2 for 5 minutes causes a 12% and 15% decrease in the diameter of the large retinal arteries and veins, respectively, and also results in a decrease in retinal blood flow of approximately 64%. Carbon dioxide has been found to diminish the vasoconstrictive effect of high O 2 concentrations. 9 Carbogen is therefore used in the treatment of central retinal artery occlusion in the hope that it will cause a smaller decrease in vessel diameter and blood flow than 100% O 2

Choroidal blood flow in the foveal region of the human ocular fundus

Purpose. To develop a noninvasive method for the investigation of choroidal blood flow (ChBF) and its regulation in the foveal region of the human ocular fundus. Methods. Measurement of ChBF was based on the technique of laser Doppler flowmetry (LDF). Sixteen normal subjects (age range, 20 to 64 years), with normal eye examination results, were asked to fixate on a diode laser beam (wavelength = 811 nm, 60 //W at the cornea) delivered to the undilated eye through a fundus camera. Light scattered by red blood cells in the tissue volume sampled by the incident laser beam was detected at the fundus image plane of the camera by an optical fiber. The diameter of the beam at the fundus of the emmetropic eye was about 300 fxm. Relative ChBF was measured in both eyes by analyzing the Doppler signal with commercial skin blood flowmeters. The average pulsatile component of ChBF, ChBFp, was determined over the cardiac cycle, and its value was compared to the average total ChBF, ChBF AV . Responses of ChBF to various physiological stimuli, such as increased blood O 2 and CO2 concentrations, rapid increases in intraocular pressure, and valsalva maneuvers, were documented. Results. Significant correlations were obtained between the ChBF AV values measured with both flowmeters (P < 0.001) and between the ChBF AV values measured in the right and left eye (P < 0.001). ChBFp represented less than 23% of ChBF AV . ChBF AV was not significantly affected by 5 minutes of breathing 100% oxygen. Raising end-tidal CO2 in one subject from 37 to 59 mm Hg increased ChBF AV by approximately 40%. Acute elevation of the intraocular pressure by suction cup or finger pressure on the globe reduced ChBF AV by as much as 90%. Valsalva maneuvers induced reproducible responses that were very different from those recorded from the skin microcirculation. Conclusions. Although LDF of the choroidal circulation is still at an early stage of development, this noninvasive method appears to provide continuous and sensitive measurements of relative choroidal blood flow in the foveal region of the human fundus. Near-infrared laser diodes enable measurements through undilated pupils. Examples of responses suggest new avenues in the investigation by LDF of the effect of various physiological stimuli, pharmacologic agents, and pathologic processes on the choroidal circulation in man. Invest Ophthalmol Vis Sci. 1994; 35:4273-4281. JL he lack of a noninvasive technique to measure choroidal blood flow (ChBF) in humans has compelled researchers to acquire information on this important hemodynamic parameter from studies in anesthetized animals. Numerous techniques have been used for thi