An oneiropenic account of an ophthalmological career.
The author has done pretty much what he wanted to do throughout his professional life. Little harm resulted. A few findings may survive.
Anecdotes as Topic↗
Biomedical subjects
D M Maurice
Publications and source records attributed to D M Maurice.
The Von Sallmann Lecture 1996: an ophthalmological explanation of REM sleep.
The hypothesis is advanced that the purpose of the eyeball movements during REM sleep is to stir the aqueous humor behind the closed lids and so avoid the risk that its stagnation could cause corneal anoxia. The relevance of the hypothesis to evolutionary biology and intensive care nursing is discussed.
Aqueous Humor↗
The regurgitation of large vitreous injections.
The same quantity of fluorescein labelled dextran was injected into the vitreous humor of 5 rabbits; in one eye, dissolved in 10 microliters solution and in the other, 100 microliters. The level of fluorescence in the two eyes was compared a few days later and found to average only 12% less with the larger volume. It is concluded that regurgitation through the needle hole can be ignored in spite of the very high intraocular pressure created by the 100 microliter injection.
Animals↗
The fate of scleral grafts in the cornea.
There have been reports of the clearing of sclera that has been grafted into the cornea. This clearing was studied in the rabbit by transplanting full-thickness scleral buttons or by implanting slivers of sclera, both autografts and allografts, into the cornea. Some clearing around the edges of the implanted scleral tissues was observed to take place slowly over the following months. Electron microscopic observation of the borders of either type of graft showed that the collagen fibrils of the sclera were breaking down either by unraveling into smaller fibrils similar in diameter to those of the cornea by fraying into microfibrils. Attracting blood vessels over the scleral slivers did not appear to accelerate the changes. Both active macrophages and fibroblasts could be found in the transitional area.
Animals↗
Local pressure effects on vitreous kinetics.
Fluorescein (F) or carboxyfluorescein (CF) was injected subconjunctivally in rabbits and its penetration into and subsequent loss from the vitreous body and anterior segment was measured. Pressure was applied over the site of the injected dye, sufficient to close down the local choroidal circulation. This raised the penetration of F about 30 times and delayed its loss, and raised the penetration of CF about seven times without affecting its loss rate. Cooling the tissue, in addition to local pressure, had little additional effect on the penetration. When F was made to penetrate by transcleral iontophoresis, pressure over the site had no effect on its kinetics. This behavior was compared with the predictions by a mathematical model in which the dye was released as a pulse at the inside of the retina and then diffused freely in the vitreous, loss occurring at the retinal surface by an outward transport process. Two experimental observations, the time at which the fluorescence behind the lens reached its peak and its subsequent loss rate, were related in a graphical representation to two physiological parameters, the rate of diffusion of the dye in the vitreous body and the outward permeability of the retinal layer. In some sets of experiments, particularly those in which iontophoresis was used, the kinetics conformed well to the predictions of this model. In other cases, the agreement was poor, and mechanisms such as storage of dye in the retina and its penetration into the vitreous by an anterior pathway appear to play a role.
Animals↗
Poor mixing of microdrops with the tear fluid reduces the accuracy of tear flow estimates by fluorometry.
The initial rapid fall in tear film fluorescence after instilling a 1 microliter drop of fluorophore could be a result of stimulated tear flow or of distribution of the dye throughout the tear fluid present in the conjunctival sac. An attempt was made to decide this by comparing the fall in fluorescence of two different fluorophores instilled at an interval of several minutes. In fact, very few patterns of initial rapid loss were found, but it was noted that there was usually a strong gradient of fluorescence from side to side across the cornea that took several minutes to dissipate. It seems that lateral mixing of a microdrop with the tear fluid is not instantaneous and that caution should be exercised in interpreting such measurements to estimate the total volume of tear fluid.
Conjunctiva↗
Fluorometric measurement of light absorption by the rabbit cornea.
A bench specular microscope, modified to perform as a scanning microfluorometer, was used to make simple and precise measurements of the absorption of visible light by the isolated rabbit cornea. The tissue was scanned while identical FITC dextran solutions were perfused over both the surfaces, and the measured fluorescence levels in the solutions on the two sides were compared. The alteration in level corresponds to the difference between the absorption of the cornea and that of of an equal thickness of the solution, which was determined in a separate experiment. The absorption of light at 500 nm ranged from 0-8% with a mean of 3.3% (n = 20; S.E. = 0.52). Pigmented and non-pigmented rabbits did not show any clear difference in absorption. These results suggests that light absorption is not a major source of error in anterior segment fluorophotometry.
Absorption↗
Mixing of the tear film under the eyelids.
Explore the source record for details and available documents.
Conjunctiva↗
The effect of age on the penetration of fluorescein into the human eye.
The penetration into the eye of fluorescein from a normal drop was found to increase with age and averaged twelve times more in the elderly than in the young. Examination of the literature suggests that this is a result of a greater contact time with the cornea rather than a rise in epithelial permeability.
Adolescent↗
Short-term reproducibility of impression cytology.
Goblet cell impressions free from epithelial cells could be collected more consistently from the rabbit conjunctiva by creating a space between the applied cellulose acetate filter and the tissue surface. Successive impressions taken over the same region of the conjunctiva could not be matched. When tight control of the area being sampled was established, the impressions left by cells on successive filters varied widely in intensity.
Animals↗
Use of fluorometry in assessing the efficacy of a cation-sensitive gel as an ophthalmic vehicle: comparison with scintigraphy.
Gelrite, a heteropolysaccharide that forms a gel in the presence of cations, was tested in humans for its efficacy as an ophthalmic vehicle by a nonivasive fluorometric technique. Fluorescein was used as the tracer, and its concentration in the anterior chamber was used as the principal measure of bioavailability. The gel afforded a twofold increase in penetration of fluorescein compared with an isotonic buffer solution; this increase is slightly more than can be obtained with simple viscous vehicles. The increase in penetration caused by Gelrite was confirmed by measurements of the contact time of fluorescein in the tear film with the cornea. Earlier experiments with scintigraphy suggested a considerably greater contact time of fluorescein with the cornea when Gelrite was used. However, this increased contact time may be because the technique also measures radioactive tracer that had dried out on the lid margins. Accordingly, significant quantities of fluorescein could be eluted from the lids after the penetration experiments were completed.
Adult↗
A microfluorometer for measuring diffusion of fluorophores across the cornea.
A microscope has been modified to a confocal spatially scanning fluorometer so that the concentration profile of a fluorophore across an isolated cornea can be measured. A slit of light is focused through one half of the objective to excite fluorescence. A confocal slit is placed at the image-plane of the microscope to collect the fluorescent light from the tissue which passes through the other half of the objective. The fluorescent light falls on to the cathode of a photomultiplier whose output is amplified by a lock-in amplifier. Scanning across the cornea is achieved by a stepper motor coupled to the fine focus of the microscope. The performance of the instrument has been assessed by studying the transport of fluorescein, carboxyfluorescein, and rhodamine B through intact rabbit corneas. A depth resolution of about 10 microns has been achieved with a 40x objective. This resolution is sufficient to determine concentration gradients in the epithelium as well as the stroma and to partially resolve the endothelium. The potential errors in the technique, resulting from limited resolution, light scattering and absorption, quenching of fluorescence, and binding of the fluorophores, are discussed.
Animals↗
The loss of fluorescein, fluorescein glucuronide and fluorescein isothiocyanate dextran from the vitreous by the anterior and retinal pathways.
The pathways by which fluorescein (F), fluorescein glucuronide (FG) and fluorescein dextran (FD) leave the vitreous body of the rabbit were examined by measuring the concentration distribution of the injected fluorophores in sections of the frozen eyes. The contours of F, as already known, show that it leaves the vitreous predominantly across the retinal surface. Mathematical analysis of the concentration gradient leads to an average outward permeability coefficient of 1.4 x 10(-3) cm min-1 for the retinal layers. The contours of FG and FD show that they leave predominantly by diffusion into the posterior chamber, encountering only a minor barrier at the anterior hyaloid membrane. The anterior contours indicate that there can be no substantial posteriorly directed fluid flow through the vitreous; if it occurs its velocity across the retinal surface must be less than 2 x 10(-5) cm min-1. The contours of FD near the posterior pole of the retina suggest that such a flow may be taking place. Some time after the systemic administration of F, an analysis of the rate of loss of fluorescence from the vitreous body shows that this corresponds to the movement of FG out through the anterior chamber. Its value bears little relationship to the condition of the blood-vitreal barrier.
Animals↗
The kinetics of tear fluid under the lower lid.
A very small drop of fluorescein solution was placed at the bottom of the lower fornix in human volunteers and its appearance in the tear film was measured. This was quite variable, but its appearance time averaged about 4 min and the peak of fluorescence 8 min. The time was shortened by blinking. The appearance time was too fast to be accounted for by simple diffusion in an unmixed tear fluid. Under normal circumstances, the release of the dye from the fornix is faster than its loss from the conjunctival sac, so that it does not seem to be a controlling factor in this loss.
Adult↗
Loss of fluorescein across the conjunctiva.
The rate of disappearance from the tear film of fluorescein and rhodamine dextran instilled together into the human eye was compared. In many cases fluorescein disappeared more rapidly, which was attributed to its penetration across the conjunctival surface. A corresponding mean fluorescein permeability across this surface of 2.5 x 10(-5) cm min-1 was calculated. This route of loss of fluorescein from the tears leads to an average overestimate of tear turnover of 25%.
Adult↗
Synchrotron x-ray diffraction studies of the cornea, with implications for stromal hydration.
The intermolecular and interfibrillar spacings of collagen in bovine corneal stroma have been measured as a function of tissue hydration. Data were recorded from low- and high-angle x-ray diffraction patterns obtained using a high intensity synchrotron source. The most frequently occurring interfibrillar spacing varied from 34 nm in dry corneas to 76 nm at H = 5 (the hydration, H, is defined as the ratio of the weight of water to the dry weight). The most frequently occurring intermolecular Bragg spacing increased from 1.15 nm (dry) to approximately 1.60 nm at normal hydration (H approximately 3.2) and continued to increase only slowly above normal hydration. Most of the increase in the intermolecular spacing occurred between H = O and H = 1. Over this hydration range the interfibrillar and intermolecular spacings moved in tandem, which suggests that the initial water goes equally within and between the fibrils. Above H = 1 water goes preferentially between the fibrils. The results suggest that, even at normal hydration, water does not fill the interfibrillar space uniformly, and a proportion is located in another space or compartment. In dried-then-rehydrated corneas, a larger proportion of the water goes into this other compartment. In both cases, it is possible to postulate a second set or population of fibrils that are more widely and irregularly separated and therefore do not contribute significantly to the diffraction pattern.
Animals↗
Cohesive strength of corneal lamellae.
Strips of rabbit stroma were prepared, and the force required to tear them apart along their length was determined. This amounted to an average of 10 g mm-1 width of tissue and it is independent of the depth of the plane in which the splitting of the cornea takes place. It could not be determined, however, whether the cohesive strength of the tissue is due to occasional collagen fibrils binding it together, interweaving of the lamellae or enmeshing of the collagen fibrils by ground substances. Other corneas were split by blunt dissection in vivo and allowed to recover for various periods of time, when the reformed strength of the split was measured. It was found to be negligible for about 5 days and rose quickly to 0.25-0.5 of the value of the untouched cornea. No increase in the force of adhesion of the split stroma was observed if an extract of corneal epithelium or a suspension of platelets was injected into the wound.
Adhesiveness↗