Ocular blood flow and vision in healthy and glaucomatous eyes.

The differential light sensitivity (DLS) in healthy, but not glaucomatous eyes, is stable and unaffected by substantial loss of the ocular perfusion pressure resulting either from increased intraocular pressure (IOP) or from moderate to severe stenosis of the internal carotid arteries. Results of pulsatile ocular blood flow measurements provide evidence that this stability of vision in healthy eyes is dependent on autoregulation of blood flow to the retinal ganglion cell axons. The onset and progression of glaucoma is shown to be associated with instability of the DLS at discrete retinal points, which develops prior to visual loss, and with an abnormal sensitivity of the DLS to increased IOP. The abnormal fluctuation of the DLS in glaucomatous eyes and the loss of DLS induced by increased IOP and decreased ocular blood flow provides evidence of a microvascular impairment to discrete areas of the optic nerve.

Choroidal blood flow in diabetic retinopathy.

The ocular hemodynamics in diabetic patients with increasingly severe retinopathy have been evaluated using a non-invasive computerized methodology. In a group of 19 healthy volunteers the mean ophthalmic arterial pressure and the ocular pulsatile blood flow were 83 +/- 2.4 mmHg and 648 +/- 42 microliters min-1 respectively. Nine diabetics with no apparent retinopathy had ophthalmic pressures and pulsatile blood flows similar to those in the control subjects. In 11 diabetic patients with background retinopathy the mean pulsatile blood flow was 471 +/- 70 microliters min-1. Thirteen diabetics with proliferative retinopathy had a pulsatile blood flow of 210 +/- 37 microliters min-1 and abnormally low ophthalmic arterial pressures. The results provide evidence that the choroidal blood flow decreases with the severity of the retinopathy in diabetes due to increased vascular resistance and a decreased ocular perfusion pressure.

Decreased choroidal blood flow associated with retinitis pigmentosa.

The intraocular pressure pulse has been measured and used to evaluate the ophthalmic arterial pressure and the ocular pulsatile blood flow in 13 retinitis pigmentosa patients and ten similar aged healthy volunteers. The light sensitivity thresholds of the central fields of all persons were recorded using the Heijl-Krakau automated perimeter. The mean pulse amplitudes of 1.2 +/- 0.2 (26) and 2.3 +/- 0.25 (20) mmHg in the affected and in the control groups respectively differed significantly (p less than 0.001). The corresponding pulsatile blood flows were 310 +/- 24 (26) and 628 +/- 40 (20) microliters min-1. The mean ophthalmic arterial pressures in the two groups were equal. The light sensitivities in pairs of eyes of four of the patients differed substantially and in all cases the eye with the better visual performance had the higher ocular pulsatile blood flow. It is concluded that relative choroidal ischaemia is closely associated with visual loss and pigment cell degeneration in patients with retinitis pigmentosa.

Estimation of pulsatile ocular blood flow from intraocular pressure.

A relationship has been derived between intraocular pressure and pulsatile blood flow in the eye. Measurements of intraocular pressure show a time variation that is associated with the pulsatile component of arterial pressure. Experimental results provide a means of transforming intraocular pressure changes into ocular volume changes. The eye is represented by a chamber with elastic walls, a pulsatile incoming flow of incompressible fluid (blood), and a steady outgoing flow of blood. Under these conditions, the rate of pulsatile blood flow through the eye can be approximated from the instantaneous intraocular pressure measurements. Data from a healthy human eye are used to illustrate the analysis.

A new procedure for the measurement of the outflow facility in conscious rabbits.

A new procedure for measuring the outflow facility in conscious rabbits is described. The Langham pneumatic tonometer is applied horizontally against the eye; the intraocular pressure (IOP) is recorded before, during and immediately following 2 min of a pre-determined increased ocular pressure that is maintained at a fixed value by digital pressure applied through the eyelids. An increased volume of aqueous humor outflow resulting from the IOP increase is evaluated from the initial and final IOP values and the pressure volume relation for eyes of living rabbits. Close agreement in values of the outflow facilities in pairs of eyes of individual rabbits and excellent reproducibility of the procedure were found in repeated measurements made over a 24-hr period. The mean values of the IOP and the total outflow facility in 60 eyes of 30 rabbits were 20.5 +/- 0.2 mmHg and 0.17 +/- 0.01 microliter min-1 mmHg-1 respectively. Thirty minutes after an intravenous injection of acetazolamide, the IOP had decreased in both eyes of individual rabbits. This was associated with a decrease in the outflow facility and with a decrease of more than 50% in the rate of aqueous humor formation. One hour after the unilateral application of epinephrine the IOP had decreased in the treated eyes while the outflow facility remained unchanged.

The Onchocerca volvulus micro- and macrofilarial responses in onchocerciasis patients to increased dosage of diethylcarbamazine.

The response of 45 severely infected onchocerciasis patients to relatively high doses of diethylcarbamazine citrate (DEC-C) has been determined. The treatment comprised two sequential phases; the first phase comprised the topical applications of a DEC-C lotion and of the anti-inflammatory steroid betamethasone. The second phase comprised the daily oral administration of high doses of DEC-C (30 mg/kg body wt) for seven days. Onchocerca volvulus microfilarial (o.v.mf.) counts in skin snips of the 45 patients decreased by 96 +/- 1.5% after 5 days of treatment with topical DEC-C lotion. Following the administration of oral DEC, the average O.v.mf. counts in the skin snips at days 51, 97, and 143 remained decreased by 85 to 93%. The mean O.v.mf. counts in 10 nodules excised from 5 treated patients at day 77 had decreased by 93% compared to the mean O.v.mf. counts in 11 nodules taken from 5 untreated patients with similar initial O.v.mf. infection. No visual loss resulted from the treatment.

The intraocular pressure and the pupillary responses of conscious rabbits to racemic erythro-alpha-methylnorepinephrine.

The intraocular pressure and the pupillary responses in conscious rabbits to racemic erythro-alpha-methylnorepinephrine (alpha MeNE) have been investigated and its activity compared to L-norepinephrine (NE). Aqueous solutions of alpha MeNE applied topically caused dose-dependent decreases of intraocular pressure and of pupil dilatation. The maximal intraocular pressure response to alpha MeNE exceeded that to NE, and the sensitivity of the intraocular pressure response exceeded that to NE by 10-20 times. The onset of the decrease in intraocular pressure to alpha MeNE was rapid and contrasted to the slow onset of the intraocular hypotensive response to NE. Preganglionic cervical sympathotomy did not effect the intraocular pressure and the pupillary responses to either alpha MeNE or NE. Superior cervical ganglionectomy induced supersensitivity to NE but not to alpha MeNE. Studies using alpha 1, alpha 2, and beta adrenoceptor antagonists indicated that the intraocular pressure responses to alpha MeNE were mediated primarily by alpha 2 and beta adrenoceptors whereas the responses to NE were mediated primarily by alpha 1 adrenoceptors. The observations are discussed in the light of recent data of the affinities of alpha MeNE and NE to alpha 1, alpha 2, and beta adrenoceptors. The high potency of alpha MeNE compared to NE in decreasing intraocular pressure and in dilating the pupil does not correlate with their binding affinities to alpha and beta adrenoceptors. The observations support an alternative explanation that the differences in the potencies of alpha MeNE and NE are due to differences in rates of inactivation of the two compounds in the adrenergic neurone.

Non-invasive diagnosis of mild to severe stenosis of the internal carotid artery.

A prospective masked study of the Langham Ocular Pressure Pulse Amplitude Procedure was made on 20 patients with arteriographically-confirmed completely patent carotid arteries (Group 1) and on 20 patients with either unilateral or bilateral stenoses of the internal carotid arteries (Group 2). The results are compared to similar studies previously reported on 20 patients with radiographically confirmed unilateral or bilateral occlusions of the internal carotid arteries (Group 3). The intraocular pressures, the pulse/intraocular pressure relations, and the ophthalmic arterial pressures were equal in pairs of eyes of Group 1 patients, and similar to those found in normal healthy subjects. The mean ophthalmic/brachial arterial pressure ratio in Group 1 patients was significantly higher than in normal subjects. In the Group 2 patients, the intraocular pressures were normal and all the measured parameters were similar in pairs of eyes, whereas, the ophthalmic/brachial arterial pressure ratios were significantly less than in the eyes of the Group 1 patients. The degree of stenoses of the internal carotid arteries (0 to 100%) as evaluated from arteriography varied inversely with the ophthalmic/brachial arterial pressure ratios (correlation coefficient 0.85). The coefficients of the sensitivity, the specificity, and the accuracy of the ophthalmic/brachial arterial pressure ratios in identifying the presence of stenotic lesions of the internal carotid artery defined by arteriography in the 120 eyes of the three groups were 89, 80, and 86% respectively. The ability of the Procedure to identify hemodynamic lesions of less than 50% is in keeping with published results of theoretical and experimental studies of the pressure gradient across stenoses in arteries with high rates of blood flow.

Carotid occlusive disease: effect of complete occlusion of internal carotid artery on intraocular pulse/pressure relation and on ophthalmic arterial pressure.

The intraocular pressure (IOP), the intraocular pulse to pressure (pulse/pressure) relationship, and the ophthalmic arterial pressure have been measured in 20 patients with either unilateral or bilateral hemodynamically significant lesions of the internal carotid arteries (ICA) as determined from arteriography. Studies were repeated in 5 of hte patients after surgical endarterectomy on the obstructed ICA. In age matched normal subjects the pulse/pressure relations were symmetrical in pairs of eyes, and the ophthalmic arterial systolic pressure was 89.0 +/- 2.1 mm Hg; this was 66 +/- 1% of the brachial arterial systolic pressure. In 19 of 20 patients with carotid occlusive disease in this study the IOP, pulse amplitudes and the pulse/pressure relationships differed in pairs of eyes. The ophthalmic arterial systolic pressure on the sides with 95 to 100% ICA stenosis was 49.9 +/- 4.05 mm Hg, which was 33 +/- 3% of the brachial arterial systolic pressure. In the remaining eyes the degree of stenosis of the ipsilateral ICA was 36.5 +/- 7.9%; the corresponding eyes had an ophthalmic arterial systolic pressure of 70.f1 +/- 51.18 mm Hg, which was 45 +/- 4% of the brachial arterial systolic pressure. Endarterectromy of the occluded arteries caused a significant increase in the ophthalmic arterial pressure on the ipsilateral side and a smaller increase in the contralateral eye; these changes were associated with a statistically significant increase in the intraocular pulse and improvement in the pulse/pressure relation.

Onchocerciasis diagnosis and the probability of visual loss in patients with skin snips negative for Onchocerca volvulus microfilariae.

Two methods have been used to verify the diagnosis of patients living in the onchocerciasis hyperendemic region of Liberia found to have O.v. negative skin snips. The first was based on a histological and an electronmicroscopic examination of the skin to determine whether the characteristic onchocerciasis dermatitis was absent, and to compare the results with age matched subjects having minimal to densely O.v. mf infested skin. The second method involved the skin response of patients with O.v. mf negative skin snips to topically applied DEC. No O.v. mf were found in skin snips serially sectioned and examined histologically from patients in which the results of incubation studies were completely negative. Skin snips from these seemingly O.v. mf negative patients had a dermatitis, whereas no dermatitis was found in skin snips taken from subjects living in nearby nonendemic areas. Patients with O.v. mf positive skin snips responded to DEC applied topically with increased pruritus and a papular rash whose severity was proportionate to the intensity of infestation. Patients with O.v. mf negative skin snips responded to DEC applied topically with increased pruritus and developed either a localized papular rash or widely dispersed papules; confirmation of onchocerciasis in these patients was found in the identification of O.v. mf in histological sections of the papules.

Chemotherapy of onchocerciasis: a controlled clinical trial of topical diethylcarbamazine (DEC) in Guatemala.

A double-masked, controlled clinical trial was conducted in Guatemala to assess the safety and efficacy of diethylcarbamazine (DEC) lotion as compared to placebo lotion in the treatment of onchocerciasis. One hundred eighty-seven people were enrolled in this study and were followed for two months. Lotion was applied daily for seven days, then weekly for seven weeks. The decrease in mean microfilarial counts per skin snip was significantly greater in those receiving DEC lotion than for those receiving placebo lotion. The proportionate reduction in microfilarial counts was similar for people with light, moderate, or heavy microfilarial loads. Side effects were mainly related to skin changes, fever, and malaise, and occurred in nearly one-third of the people receiving DEC lotion. These reactions occurred almost as commonly in those people who were lightly infected as in those who had moderate or heavy infections.

An evaluation of currently available, noninvasive tests of carotid artery disease.

A clinical study compared compression ophthalmodynamometry, suction ophthalmodynamometry, oculoplethysmography, modified oculopneumoplethysmography, and Doppler flow studies with graded arteriography for the detection of carotid artery stenosis. Compression ophthalmodynamometry and suction ophthalmodynamometry were the most accurate tests in this series with the results of both types of ophthalmodynanometry almost identical. A new, noninvasive procedure, oculocerebrovasculometry, was also performed in a slightly different group of patients. This procedure has theoretic advantages over the others tested because it measures directly the intraocular pressure as the end point of the test.

Controlled clinical trial of oral and topical diethylcarbamazine in treatment of onchocerciasis.

In a double-blind controlled clinical trial comparing the safety and efficacy of oral diethylcarbamazine citrate (DEC) with topical DEC for the treatment of onchocerciasis twenty men with moderate skin-snip microfilarial counts received daily therapy for 1 week, then weekly therapy for the rest of 6 months. The number of microfilariae per skin snip dropped quickly to 2% of initial levels and remained at low levels in those receiving oral DEC, and to 20% of initial levels in patients treated with DEC lotion. Side-effects in both groups included lymphadenopathy, fever, pruritus, rash, proteinuria, and chorioretinitis; they were commoner with topical DEC.