Biomedical subjects
S H Sinclair
Publications and source records attributed to S H Sinclair.
The retinal venous pulse. Its relation to optic disc characteristics and choroidal pulse.
PURPOSE: The presence or absence of the spontaneous retinal venous pulse is an important clinical sign, especially when one is evaluating a patient who may have increased intracranial pressure. The purpose of this study is to evaluate a large group of healthy patients, correlating optic disc characteristics, choroidal pulse, and brachial pulse pressure with the presence and intensity of the spontaneous retinal venous pulse. METHODS: Ninety-seven patients were studied correlating these parameters with their fundus photographs. Ocular pneumotonometry as a measure of the choroidal pulse and the brachial pulse pressure were correlated with the optic disc characteristics and the intensity of the retinal venous pulse statistically. RESULTS: The results showed a highly significant correlation with these parameters. The greater the pulse amplitude--especially the choroidal pulse the more likely the spontaneous retinal venous pulse would be present. More importantly, the anatomic variable of optic disc cup and vascular configuration had the greatest influence on whether the spontaneous retinal venous pulse is present or absent. CONCLUSION: The authors conclude that unless the clinician is aware of the importance of optic nerve characteristics and pulse amplitude in the choroid (indirectly measured in a normal clinical setting by the brachial pulse) the significance of the spontaneous retinal venous pulse cannot be properly determined.
Pentoxifylline increases retinal capillary blood flow velocity in patients with diabetes.
OBJECTIVE: The purpose of this study was to determine whether oral pentoxifylline would improve retinal microvascular hemodynamics and blood rheology in patients with diabetes. DESIGN: Patients were enrolled in a double-masked, placebo-controlled trial of pentoxifylline at 2000 mg/d. Retinal capillary blood velocity and leukocyte density, filterability, viscosity, and fibrinogen content were measured by the blue-field entoptic phenomenon simulation, filtration, rotational viscosimetry, and heat precipitation techniques, respectively, before, during, and after drug therapy. RESULTS: Treatment with pentoxifylline resulted in a 23.2%, 26.8%, and 37.8% increase in capillary blood flow velocity at 1, 2, and 3 months of therapy, respectively, with a return to pretreatment baseline levels 1 month after cessation of therapy. There were no apparent effects on the remaining variables during treatment. CONCLUSION: Pentoxifylline increases retinal capillary blood flow velocity in patients with diabetes.
Macular capillary hemodynamic changes associated with Raynaud's phenomenon.
BACKGROUND: Raynaud's phenomenon is an episodic, reversible spasm of the digital arterioles. Previous studies have suggested that Raynaud's phenomenon may be associated with alterations in the ocular circulation. The authors used the blue field entoptic simulation technique to study macular retinal capillary hemodynamics in patients with Raynaud's phenomenon. METHODS: Forty-two volunteers participated in the study: 18 with a connective tissue disease and secondary Raynaud's phenomenon, 8 with a connective tissue disease and no Raynaud's phenomenon, and 16 healthy volunteers. The mean of three blue field entoptic density and velocity measurements was determined before as well as during and 10 minutes after the immersion of one hand in ice water. RESULTS: Patients with severe Raynaud's phenomenon demonstrated a statistically significant 30% decrease in retinal capillary flow during immersion of a hand in ice water (P less than 0.05), which remained 17% reduced (P less than 0.05) for at least 10 minutes after removal. The decrease in capillary flow was not observed in control individuals or in individuals with connective tissue disease who demonstrated minimal or no Raynaud's phenomenon. CONCLUSION: The prolonged reduction in retinal capillary flow observed in subjects with Raynaud's phenomenon is probably caused by retinal arteriolar vasoconstriction and is similar to concurrent arteriolar vasoconstriction reported in other systemic vascular beds. In the retina, the recurrent ischemic episodes may result in dysfunction or injury.
Idiopathic choriovitreal membrane--a case report.
A case of a macular idiopathic choriovitreal membrane is described which developed in a diabetic man. On initial examination the patient was found to have a pigment epithelial detachment with a choroidal neovascular membrane (CNVM) in the right eye. Two months after the first visit the CNVM was seen to have penetrated the retina and presented as a choriovitreal membrane. Panretinal photocoagulation was applied after which the choriovitreal membrane demonstrated fibrotic involution. This case is unusual in that the choriovitreal membrane developed in the absence of a choroidal or retinal pigment epithelial disease process that may be associated with a CNVM as well as in the absence of previous macular laser treatment.
Macular retinal capillary hemodynamics in diabetic patients.
Macular retinal capillary hemodynamics was evaluated in 39 nonhypertensive insulin-dependent diabetic patients and 24 age-matched control subjects using the blue field entopic simulation technique. A statistically significant 25% increase in macular capillary flow velocity was observed among the diabetic eyes along with a 37% decrease in the density of the entoptically perceived leukocytes. When the eyes of diabetic patients were graded according to the modified composite scale of Klein et al, capillary flow velocity was elevated in the group without retinopathy as well as in those with mild background retinopathy and those with preproliferative or proliferative retinopathy. The density of the entopically perceived leukocytes was more severely reduced in those with retinopathy than in those without retinopathy but was poorly correlated with the composite grading scale. These results are consistent with the concept that in diabetes, capillary obstruction, either transient or permanent, may focally occur within the retina associated with vasodilation in the adjacent microvasculature because of relative tissue hypoxia.
Long-term outpatient treatment of CMV retinitis with ganciclovir in AIDS patients.
Cytomegaloviral retinitis was diagnosed in nine eyes of seven patients with acquired immune deficiency syndrome (AIDS) on the basis of the characteristic ocular findings and a positive culture for cytomegalovirus (CMV) obtained systemically. Treatment with ganciclovir was begun on a protocol which provided two weeks of inpatient therapy at daily doses of 2.5 to 10 mg/kg followed by outpatient therapy at a reduced dosage three to six days per week. Outpatient maintenance dosage ranged from 15 mg/kg per week to 30 mg/kg per week. In seven eyes of six patients the treatment decreased retinal inflammation and stabilised the margins of the lesions. Six patients have tolerated long term maintenance therapy for 10-30 weeks. Six of seven patients (85%) in this study developed side effects from ganciclovir which required periods of a reduction in dosage or interruption of therapy. The side effects from ganciclovir included neutropenia, thrombocytopenia, drug fever, and neuropathy. Physicians using ganciclovir in AIDS patients must watch for the signs of drug toxicity and adjust treatment accordingly. Ganciclovir appears to be a promising therapy for CMV retinitis, but further work is necessary to determine the best regimen for optimal efficacy with minimal side effects.
Investigation of the source of the blue field entoptic phenomenon.
The cellular source of the blue field entoptic phenomenon was investigated in two microvascular preparations using video-microscopy with lighting conditions similar to those under which the entoptic phenomenon is visualized within the human eye. In the wing of the hibernating bat, microvascular flow was simultaneously videotaped under transmission illumination at 430 nm and under unfiltered illumination. In the rat cremaster alternating observations were made using transmission illumination at 430 nm and epi-illumination fluorescence microscopy with leukocytes rendered fluorescent by intravenous Quinacrine. In both preparations, low magnification video-microscopy using 430 nm illumination produced a field of particles, which were brighter than the background, flowing within a network of dark vessels. The appearance of the particles and their movement simulated the blue field entoptic particle motion. Under higher magnification, the particles appeared brighter than the plasma gaps between red blood cells and were demonstrated to be leukocytes by morphology, by specific staining and by typical behavioral movement. The particles were observed in terminal arteriols capillaries, and post-capillary venules where they were not obscured by red blood cells. The results of this study of two microvascular preparations strongly suggest that in the human eye the blue field entoptic phenomenon is produced by leukocytes flowing within the macular retinal microvasculature.
A long Krupin-Denver valve implant attached to a 180 degrees scleral explant for glaucoma surgery.
A long glaucoma valve implant attached to an external scleral explant was used during filtration surgery in 72 eyes: 39 eyes with neovascular glaucoma and 33 eyes with other types of secondary glaucomas or with primary glaucoma in which prior filtration surgery had failed. The implant consisted of an open Silastic tube (outside diameter, 0.64 mm), which was placed into the anterior chamber. The external end of the tube contained a pressure-sensitive (opening pressure, 11 mmHg) and unidirectional slit-valve, and was sutured within the groove of a #220 Silastic explant. The 180 degree explant was placed beneath three rectus muscles and then sutured so that the grooved side was against the sclera, with the anterior edge 8 to 12 mm posterior to the limbus. The long glaucoma valve implant resulted in a large, posterior bleb extending over the area of the Silastic explant. The mean preoperative intraocular pressure (IOP) of 43.9 mmHg in the eyes with neovascular glaucoma was reduced to 17.4 mmHg after a mean follow-up of 20.2 months. The mean preoperative IOP of 38.1 mmHg in the eyes after failure of previous filtration surgery was reduced to 17.6 mmHg at a mean follow-up of 21.0 months. Postoperative IOP was less than 21 mmHg in 77% of eyes with neovascular glaucoma (47% required additional medication) and in 82% of eyes with previous failure of filtration surgery (56% required additional medication).
Pupillary dilation with tropicamide 1% for funduscopic screening. A study of duration of action.
Primary care practitioners omit pupillary dilation from funduscopic examination, possibly because of time constraints, poor patient compliance, or fear of adverse reactions. Nevertheless, the omission of this procedure may lead to the inadequate visualization of the fundus for screening. We administered a topical solution of 1% tropicamide to 30 adults to determine the course of pupillary dilation over time and whether adequate dilation could be attained within a routine clinic visit. Pupil diameters were measured every 5 minutes in a 30-minute period. The initial mean pupillary diameter was 2.4 mm and the endpoint was 5.5. Dilation was significantly slower in those older than 50 years of age. However, at 15 minutes 87% of the patients, regardless of age, had achieved dilation to at least 4 mm, which should be sufficient for screening under most circumstances. We conclude that adequate pupillary dilation in adults usually can be achieved within the time frame of a routine office visit and thus should not be a deterrent to routine funduscopic screening by primary care practitioners.
Laser Doppler velocimetry study of retinal circulation in diabetes mellitus.
Bidirectional laser Doppler velocimetry and monochromatic fundus photography were used to investigate retinal circulation in 26 normal subjects and in 51 insulin-treated diabetic patients with no retinopathy, background retinopathy (BDR), proliferative retinopathy (PDR), and patients with PDR who had been treated by panretinal photocoagulation (PDR-PRP). Measurements were obtained from main temporal retinal vessels in each eye. Venous diameter at the site of laser Doppler velocimetry measurements was significantly greater than normal in patients with BDR and PDR. The maximum velocity of red blood cells was significantly lower than normal in eyes with diabetic retinopathy. Calculated volumetric blood flow rate, however, was not significantly different from normal in eyes with no retinopathy, BDR, and PDR, and was significantly decreased from normal in patients with PDR who had been treated by panretinal photocoagulation. A comparison between this technique and the fluorescein dye dilution technique is provided.
Effect of panretinal photocoagulation on retinal blood flow in proliferative diabetic retinopathy.
The effect of panretinal photocoagulation (PRP) on retinal volumetric blood flow rate and its regulatory response to hyperoxia was investigated in a main temporal vein of 15 eyes with proliferative diabetic retinopathy, using bi-directional laser Doppler velocimetry and monochromatic fundus photography. At an average of 4 +/- 2 months after the beginning of PRP, retinal venous diameter decreased from an average of 174 +/- 20 micron to 162 +/- 19 micron (P less than 0.01), red blood cell velocity decreased from 1.3 +/- 0.4 cm/sec to 1.1 +/- 0.4 cm/sec (P less than 0.01), and blood flow decreased from 11.5 +/- 3.8 microliter/min to 8.4 +/- 3.3 microliter/min (P less than 0.001). The regulatory response to hyperoxia, characterized by the percentage decrease in retinal blood flow during 100% oxygen breathing, improved from 20 +/- 15% prior to treatment to 45 +/- 12% following treatment (P less than 0.001). The decrease in retinal blood flow is most likely due to a decrease in viable retinal tissue and an improvement in retinal oxygenation following PRP. The increase in the regulatory response to 100% O2 breathing following PRP may also result from such an improved retinal oxygenation.
Retinal blood flow autoregulation in response to an acute increase in blood pressure.
The response of the retinal circulation to an acute elevation in systemic blood pressure was studied in three healthy normotensive volunteers using the noninvasive laser Doppler velocimetry (LDV) technique combined with retinal vessel size measurements. Isometric exercise was employed to induce the acute rise in arterial pressure. There was no detectable change in retinal blood flow until the mean brachial artery blood pressure was elevated to an average of 115 mm Hg, which represented an average rise in mean blood pressure of 41% above baseline values. Above this value, blood flow increased along with further increments in blood pressure. The parallel rise between the ophthalmic artery pressure and the brachial artery pressure indicates that the regulation of retinal blood flow observed in the above mentioned pressure range is achieved through an increase in retinal vascular resistance rather than by a mechanism that would act to maintain a constant ocular perfusion pressure.
Rubeola retinopathy and pigmented paravenous retinochoroidal atrophy.
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Does topical phenylephrine, tropicamide, or proparacaine affect macular blood flow?
The acute effect of topical phenylephrine HCl 10%, tropicamide 1% and proparacaine HCl 0.5% on macular capillary blood flow was studied in six healthy human volunteers using the blue field simulation technique. This technique provides a method for quantifying the velocity of leukocytes flowing in one's own retinal macular capillaries. Patients adjusted the velocity of computer simulated leukocytes moving on a CRT screen to match that of their own entoptically perceived leukocytes before instillation of each of the tested preparations and for 35 minutes immediately thereafter A 5% NaCl solution was used as a control. We found no significant difference in leukocyte velocity between the control drop and any of the tested drugs. With the six subjects tested, the calculated average minimum percentage change in leukocyte velocity detectable with this technique (P less than 0.05, paired t-test) was 9%. None of the tested drugs affected macular leukocyte velocity, and presumably blood flow, by more than this amount.
Diabetic nephropathy in pregnancy.
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Retinopathy in the pregnant diabetic.
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Blood velocity and volumetric flow rate in human retinal vessels.
The distributions of blood velocity and volumetric flow rate in individual vessels of the normal human retina were determined as a function of vessel diameter. The mean velocity of blood, Vmean, was calculated from the centerline velocity measured by bidirectional laser Doppler velocimetry (LDV). Volumetric flow rate was determined from Vmean and the vessel diameter, D, measured from monochromatic fundus photographs. Diameter of the arteries and veins at the site of the LDV measurements ranged from 39 to 134 microns and 64 to 177 microns, respectively. Flow velocity correlated with D (P less than 0.001 for both arteries and veins). Volumetric flow rate varied with D at a power of 2.76 +/- 0.16 for arteries and 2.84 +/- 0.12 for veins, in close agreement with Murray's law. Calculated from 12 eyes, the average total arterial and venous volumetric flow rates were 33 +/- 9.6 and 34 +/- 6.3 microliters/min, respectively. The good agreement between both flow rates suggests that the technique and the assumptions for calculating flow yield results that satisfy mass conservation. Total arterial and venous volumetric flow rates correlated with total arterial and venous vessel cross-section. Volumetric flow rate in the temporal retina was significantly greater than in the nasal retina, but the difference is likely to be due to the larger area of the temporal retina. No difference in flow rate was observed between the superior and inferior retinal hemispheres. Finally, blood velocity in the major retinal vessels measured under normal experimental conditions appears remarkably constant over short (hours) and long (months) periods of time.