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R W Flower

Publications and source records attributed to R W Flower.

At least 37 records · Page 2Linked to original sources

An image processing approach to characterizing choroidal blood flow.

Indocyanine green (ICG) dye angiography has made possible routine visualization of choroidal blood flow in the human eye; however, to date, its clinical utility has been limited. An overlying layer of densely pigmented tissue and the complex, multilayered vascular structure of the choroid combine to produce angiographic images of low contrast which are difficult to interpret. Conventional image processing can enhance individual images of the blood vessels, but this approach contributes no information about the dynamics of blood flow. Using relatively inexpensive, commercially available personal computer hardware, angiographic image processing algorithms were developed which appear to characterize uniquely a subject choroid in terms of various blood flow parameters. We believe this to be the first successfully demonstrated approach to routinely characterizing the human choroidal circulation in a way that conserves spatial distribution of blood flow dynamics across the entire observed choroidal area. The computer system allows acquisition of digital images from photographic film negatives; alternatively, real-time direct digitization of images from a high-resolution video camera is possible. Once acquired, the digitized data are manipulated according to various algorithms that employ time-sequence analysis to generate two-dimensional curves or three-dimensional surfaces which characterize the choroidal circulation. The unique correspondence of each three-dimensional surface to the subject choroidal circulation from which it was derived is demonstrated. Grouping the characteristic three-dimensional surfaces according to various topographic features in common may provide a basis for discriminating between normal and abnormal choroidal circulations.

Animals↗

Physiology of the developing ocular vasculature.

A conservative view of some of the data discussed here would be that they are anecdotal, but the possibility that factors other than oxygen alone contribute to genesis of ROP is compelling, as is the possibility that clinically observed ROP is only a narrow range of a broad spectrum of retinopathies that could be produced in the immature retina were appropriate physiologic parameters varied outside the current clinically acceptable range. In this context, the significance of such preliminary investigations as these is that they should alert investigators and clinicians to look for correlations between incidence of ROP and factors other than oxygen alone.

Animals↗

Visualization of a developing vasculature.

The events involved in vasculogenesis still remain obscure. One difficulty has been the techniques employed to visualize angioblasts, i.e., vascular precursors, during the genesis of blood vessels. The retina provides a unique model for studying these events since it is not completely vascularized in some mammals at birth. Using a previously published magnesium-dependent ATPase technique to visualize the developing retinal vasculature and its precursors, and embedding this tissue in JB-4 methacrylate for serial sectioning, has permitted examination of the retinal vasculogenic processes in dual perspective. The technique has permitted observation of the stages in angioblast differentiation and the apparent importance of glycosaminoglycan-rich cell-free spaces in this process. Perhaps the most important observation is that initial vessel formation occurs by coalescence of angioblasts after differentiation in situ.

Adenosine Triphosphatases↗

Ten years experience with choroidal angiography using indocyanine green dye: a new routine examination or an epilogue?

The choroidal circulation can be studied by an angiographic technique which utilizes near-infrared light wavelengths and a biocompatible dye, indocyanine green (CardiogreenR). Near-infrared light is less absorbed than visible light by the pigment epithelium and the macular xanthophyll, and indocyanine green (ICG) dye doesn't leak from the choriocapillaris as sodium fluorescein dye typically does. Due to the high rate of choroidal blood flow, a fundus camera adapted with special filters and a continuous light source was used in order to make angiograms at the rate of 10 per second. Our experience at the Wilmer Institute and the Eye Clinic at St. Gallen includes 180 choroidal angiograms of normal volunteers and approximately 500 choroidal angiograms of patients with several fundus diseases, mainly senile macular degeneration, diabetic retinopathy and choroidal tumors. Although many of our results are preliminary, we present them to demonstrate the potential applications of this method in ophthalmology. Some factors which may have inhibited an extensive propagation of clinical choroidal angiography in the past are also discussed.

Aged↗

Postnatal retinal vascular development of the puppy.

Retinal vascular development during the first three postnatal weeks was studied in 63 purebred beagle puppies. Use of a positive enzyme histochemical reaction for adenosine triphosphatase in the nuclei and nucleoli of vascular cells made visualization of the retinal vasculature possible. Animals were killed by decapitation. Thus, artifacts resulting from use of anesthetics or tracer substances were avoided. In general, this study demonstrates important similarities between canine and human retinal vascular development, and this gives further reason to use of the puppy retina as a superior model for studying retrolental fibroplasia pathogenesis. This staining technique demonstrates undifferentiated cells in the avascular retina that appear to be vascular precursors or angioblasts. Primordial vessels form by organization of differentiating angioblasts that exist in peripheral retinal cystic spaces at birth, or by addition of fully differentiated endothelium; they form unlike neovascularization. Müller cell processes appear to provide a structural matrix throughout the avascular puppy retina on which differentiated angioblasts organize into a vascular network. Arteries develop in beds of primordial capillaries lying near the leading edge of the developing vasculature. This precedes vein formation which occurs through a process involving coalescence of embryonic capillaries which themselves were derived from primordial capillaries. Preliminary examination of eight mongrel kitten retinas prepared by this method clearly indicates that the puppy retina is much more completely vascularized at birth than that of the newborn kitten. Moreover, the rate of postnatal retinal vascularization is significantly faster in the kitten. The kitten vasculature does appear to form by the organization of angioblasts as in the puppy, but kitten angioblasts have a different appearance from those in the puppy.

Adenosine Triphosphatases↗

Foreign body granulomas in normal ovaries.

In 100 consecutive cases in which grossly normal ovaries were removed at the time of pelvic surgery, 9% were found to contain crystalline foreign particles. An additional 9% contained cortical granulomas. In four of six cases, computer-assisted x-ray analysis of the crystalline foreign particles was successful and revealed magnesium and silicon.

Adult↗

Prostaglandins as mediators of vasotonia in the immature retina.

In vivo observations of the immature beagle puppy retina indicates that in general O2-breathing induces vasoconstriction whereas CO2 or CO2 combined with O2 induces vasodilation. It was the goal of this study to determine whether a specific correlation could be found between this pattern of vascular response to changes in blood gas content and production of prostaglandins in the eye. Prostaglandin production by puppy choroidal and retinal tissues and platelets exposed in vitro to these gas combinations was such that it appears platelet-derived thromboxane could have a significant influence in determining retinal vasotonia.

Animals↗

Scanning electron microscopic studies of the hyaloid vascular system in newborn mice exposed to O2 and CO2.

It has been suggested that the tunica vasculosa lentis of newborn mice undergoes vasoproliferation after oxygen exposure and might be used as an experimental model for intraocular neovascularization. A scanning electron microscopic technique which provides visualization of the entire hyaloid vascular system was used to study its response in mice exposed to various gas mixtures (70% O2/30% N2, 10% CO2/90% air, 10% CO2/70% O2/20% N2). Marked differences were found between hyaloid regression in gas exposed mice compared to air control mice, but no evidence of neovascularization was found in any group. The data support the possibility that changes in the hyaloid may be the consequence of the hydrostatic coupling which exists between this atrophic, possibly flow-resistant vasculature and the developing retinal vasculature whose blood flow characteristics are significantly altered by exposure to CO2 and O2.

Age Factors↗

Platelet-fibrin embolism in a rhesus macaque: angiographic and pathologic studies comparing fluorescein and indocyanine green.

A male rhesus macaque was found to have what appeared to be numerous platelet-fibrin emboli in retinal vessels in the perimacular area. Indocyanine green (ICG) dye fluorescence and fluorescein angiograms of the fundus demonstrated leakage of fluorescein, but not ICG, from the involved arterioles. Histopathologic changes in the eyes included occlusion of retinal and choroidal vessels with platelet-fibrin emboli, inner retinal ischemia, ischemic injury to the parafoveal capillary bed distally to occlusion of precapillary arterioles, and retinal exudate limited to the regions of capillary damage. Differential leakage of fluorescein may be explained by the difference in binding affinities of the 2 dyes to blood protein: 20% to 40% of the circulating fluorescein is unbound, and 98% of ICG is bound to serum albumin. Simultaneously or serially performed angiograms with fluorescent probes of different sizes might be used to obtain a qualitative measure of vascular integrity in persons with embolism, diabetic retinopathy, sickle cell retinopathy, vasculitis, and other disorders known to produce focal retinal and choroidal vascular occlusion.

Animals↗

Long-term continuous monitoring of intraocular pressure in conscious primates.

A technique for chronic implantation of a device for long-term continuous, quantitative monitoring of intraocular pressure (IOP) in experimental animals is presented. The methodology employed is straight forward and should be easily duplicated for experimental investigations where such monitoring might be useful. Continuous IOP data recorded from the device implanted in a conscious adult rhesus monkey are compared with continuous IOP data reported by other investigators.

Animals↗

Retrolental fibroplasia: evidence for a role of the prostaglandin cascade in the pathogenesis of oxygen-induced retinopathy in the newborn beagle.

Aspirin administration, at a dosage producing plasma levels within the human therapeutic range, caused marked inhibition of production of both vascular prostacyclin (a vasodilator) and platelet thromboxane (a vasoconstrictor) in beagle puppies. In addition, aspirin-treated, oxygen-exposed puppies developed retinopathy of significantly greater severity than their unmedicated, oxygen-exposed littermates. Direct ophthalmoscopic observations indicated that whereas sustained oxygen breathing produced retinal vasoconstriction in unmedicated puppies, retinal vessels of aspirin-treated littermates became more dilated or remained unchanged. It is postulated that retinal vasoconstriction may be a normal physiologic mechanism to protect the immature retina from damaging effects of high blood oxygen levels; i.e., it may be a protective rather than a pathologic process in response to hyperoxia. Many vascular anomalies which characterize the human disease were present in the retinas of the puppies. Several of the most severely affected puppies treated with aspirin even displayed grade III cicatricial retinopathy (falciform retinal fold). Thus, a major criticism of the retrolental fibroplasia animal model has been addressed by producing cicatricial retrolental fibroplasia in puppies, and the confidence with which results from experimental animal studies might be extrapolated to the clinical situation is thereby strengthened.

Animals↗

Analysis of the retina via suprafusion electroretinography.

Electroretinographic (ERG) transient responses elicited in monkeys by abrupt changes in the periodicity of a rapidly intermittent (suprafusion) luminance stimulus were studied experimentally, and analyzed and interpreted through a theory of dynamic retinal responses. The suprafusion ERG transients are confirmed to behave in accord with theoretical expectation, as elemental responses (retinal Green's functions). By aid of the theory the ERG wave-forms can be reduced to two significant elements. One element, accounting for approximately two-thirds of the total ERG variance, is strictly linear, and correlates well with simultaneously evoked cortical (VEP) transients which were previously related to suprafusion perception in humans. The other element, comprising approximately one-third the ERG transient, is a rectification, with properties indicating that it may arise from a specific layer of retinal neurons (amacrine cells); on this assumption the theory demonstrates that high-frequency nonlinear ERG flicker can isolate activities proximal and distal to the rectifying (amacrine) layer. Thus, the hypothesis of an amacrine origin for the rectifying element entails the possibility that suprafusion ERG studies could accomplish in vivo "dissection" of the human retina.

Animals↗

Indocyanine green fluorescence angiography.

Indocyanine green (ICG) fluorescence angiography has been further refined for use in both laboratory and clinical investigations. In the present modification of the Zeiss fundus camera all lenses except the aspherical objective lens have been specially antireflection coated to increase light transmission in the spectral region around 800 nm. A 300 watt indium iodide lamp continuous light source has replaced the conventional xenon flash lamp. This light source produces a retinal irradiance of 265 mw, and therefore restricts retinal exposure time to 11.9 seconds, but that time is more than adequate to record passage of dye through the choroid. Spatial resolution of the fundus on the film has been increased from 11.7 microns to 7.4 microns. With these technical refinements the choroidal circulation can be studied at 20 frames per second, which is adequate to document the very rapid movement of blood through the vasculature. ICG angiography may change our interpretations of choroidal circulatory phenomena which are now based on fluorescein angiography, and it clearly is an effective tool in laboratory (experimental) investigations.

Animals↗

The mechanism of optic nerve damage in experimental acute intraocular pressure elevation.

We produced intraocular pressure (IOP) elevations in 32 primate eyes and studied retinal ganglion cell rapid axonal transport with autoradiography and electron microscopy. Animals breathing room air at sea level pressure were compared to animals breathing 100% oxygen at 3 atm pressure in a hyperbaric chamber. Despite major increases in arterial oxygen levels in the hyperbarically oxygenated animals, both groups had axonal transport blockade at the optic nerve head. Anoxia appears not to be the most important cause of acute axonal damage induced by elevated IOP. The pattern of axonal abnormality within individual fiber bundles at the optic nerve head provides support for mechanical compression as a more likely alternative cause for induced neural damage.

Animals↗