[Retinal hazard from blue light emitting diode].

PURPOSE: To compare the effect of exposure time from a blue(460 nm) light emitting diode(LED) on the morphology of the outer retina and determine conditions where damage occurs. MATERIALS AND METHODS: Young adult rhesus monkeys were anesthetized, and received blue LED exposure from a modified slit-lamp. A 3 mm beam of 0.85 mW was imaged onto the retina through a lens positioned before the cornea and exposure damage was determined at time intervals for 12 to 90 min. Fundus photography, fluorescein angiography(FAG), retinal tomography(HRT), and s-cone electororetinogram(S-ERG) were recorded at baseline, 2, and 30 days. RESULTS: Two days after 40 min exposure, there was a grey, discolored region, which was over-fluorescent in FAG, and an incresse in HRT and S-ERG corresponding to the site which was exposed to LED light. In histological examination at 30 days, the LED had caused produced a marked disruption of the disks of photoreceptor cells, damaged retinal pigment epithelium(RPE) apical villi, and a loss of RPE melanin after 90 min exposure. CONCLUSION: A threshold level was found around 40 min. This morphological damage may impair function and continuous exposure to blue light is potentially dangerous to vision.

Primary open angle glaucomas in the rhesus monkey.

Rhesus monkeys from the closed Cayo Santiago colony of the University of Puerto Rico demonstrate elevated (> or = 22 mm Hg) intraocular pressure in a pattern which significantly favours certain maternal lineage groupings. The colony had remained genetically pure since 1938. Of nine matriarchal lineages (matrilines) examined, two had an incidence of ocular hypertension of more than 40% and six of more than 10%. Information on 18 matrilines is currently located in the colony data base which identifies each individual and its vital statistics. In 1990, six animals were moved to the laboratory in Florida. Among those from a low incidence matriline, we found abnormal optic nerve cups, pallor, reduced function of (mainly peripheral) fields, progression and loss of optic nerve axons in the presence of ocular hypertension. In another individual where the cup/disc ratio for the right eye was 0.7 and left eye 0.4 and outflow facility was normal, we excluded all other causes of optic nerve atrophy, and low tension glaucoma was diagnosed. This female was from a matriline with a low incidence of ocular hypertension. Relatively rapid aging (3-4 years/human year) monkeys with ocular hypertension and familial clustering produce a near ideal glaucoma research model.

A primate model for age related macular drusen.

A closed colony of semi-free-ranging rhesus monkeys maintained in isolation since 1938 by the Caribbean Primate Research Center (CPRC) is being studied as a model for age related macular drusen. Of examined colony animals 57.7% of the monkeys and 47.3% of their eyes have drusen. The prevalence and severity of drusen are linearly related to increasing age and are significantly higher in specific maternal lineages (matrilines). An electrophysiological estimate indicates loss of function associated with drusen. Prevalence of drusen in CPRC females is almost twice that of males, while the prevalence among CPRC animals in general appears to be several times that of monkeys from continental US facilities. Evidence suggests that the frequency of endstage lesions is also similar to that in human populations. The CPRC matriline monkeys appear to provide the best model yet reported for human age related macular drusen.

Maintenance of myelinated fibre g ratio in acute experimental allergic encephalomyelitis.

The spectra of myelin sheath thickness and g ratio (axon diameter/fibre diameter) of guinea pig optic nerves for 8 animals with acute experimental allergic encephalomyelitis (EAE) were compared with those for 6 normal animals. The mean myelin sheath thickness of 0.12 microns for the animals with EAE was significantly lower than the value of 0.16 microns for the normal animals. Since fibre diameter comprises axon diameter plus the thickness of its surrounding myelin sheath, a reduction in mean fibre diameter from 1.52 microns in normals to 1.20 microns in EAE was expected, but it was surprising to find that a mean g ratio of 0.85 obtained for normal nerves was not substantially different from a value of 0.86 for demyelinated optic nerves. A decrease in the mean axon diameter of 1.24 microns for normal animals to 0.94 microns for those with EAE tended to offset the decrease in mean myelin sheath thickness and contributed to the relative stability of the g ratio with acute demyelination. Our results showing reduction in axonal calibre and myelin sheath thickness may offer an explanation for apparent discrepancies between electrophysiological delays in conduction characteristics of experimental and, if not the result of a maturational effect on myelination, human primary demyelinating disorders associated with the scant histopathological demyelination of initial attacks of EAE and the visually asymptomatic patients with multiple sclerosis.

The effect of age and ethnic background on the natural rebleed rate in untreated traumatic hyphema in children.

Controlling the natural tendency to rebleed in this condition is important because the serious vision threatening complications usually follow rebleeds. In evaluating treatments, it has been difficult to determine the natural rebleed rate. Recent reports on traumatic hyphema suggest that the natural rebleed rate in this condition may be higher in blacks and young children than in Caucasians and older children and adults. The records of 38 patients who were admitted to a children's hospital and who were the untreated control group in a previous study on systemic steroid treatment for traumatic hyphema, were reviewed to determine their ethnic background and age. The data was examined to see if these characteristics were related to the rebleed rate. The overall rebleed rate in this untreated group was 32% (12 out of 38). For specific ethnic groups, the rebleed rate was: Caucasians, including presumed Hispanics--32% (10 out of 31); Caucasians, not including presumed Hispanics--33% (8 out of 24); presumed Hispanics--29% (2 out of 7). There was no statistically significant (P greater than .95) difference in rebleed rates. With regard to age, the rebleeding rate was 54% (6 out of 11) for children under six years of age, and 22% (6 out of 27) for those over six years of age. This was a statistically significant difference (P less than .05). Ethnicity, therefore, in this group of untreated patients did not affect the natural rebleed rate. Younger age, under six years, is associated with a higher natural rebleed rate in traumatic hyphema, and these children should be most carefully treated.

Spectra of G ratio, myelin sheath thickness, and axon and fiber diameter in the guinea pig optic nerve.

The spectra of fiber and axon diameter, myelin sheath thickness, fiber density, and g ratio of the optic nerve were analyzed for the strain-13 guinea pig, an animal extensively utilized in the investigation of experimental disorders of demyelination. Our detailed analytical study of the normal guinea pig optic nerve provides the basis for comparison to disease states and the morphology of other species. As in the rat, mouse, and chipmunk, fiber diameters in the guinea pig were unimodal, but dissimilar to the trimodal fiber spectra of the cat and primate. The predominance of medium-sized fibers (0.80-2.00 microns), common to most species, contributed to the larger mean fiber diameter (1.45 microns) of the guinea pig optic nerve, in which small fibers (0.50 microns or less) were infrequent and fibers larger than 5.00 microns in diameter, seen in the cat and primate, were absent. While myelin sheath thickness increased with axon diameter in the guinea pig, as in other species, a g ratio of 0.81 in the guinea pig was greater than in most mammals. Since conduction velocity is dependent on axon size, as well as myelin properties, the relatively larger mean axon diameter of the guinea pig optic nerve (1.18 microns) may compensate for the decrease in its myelination.

Antioxidant enzymes reduce loss of blood-brain barrier integrity in experimental optic neuritis.

We studied the effect of antioxidant enzymes on the loss of integrity of the blood-brain barrier in the optic nerves of strain-13 guinea pigs with chronic experimental allergic encephalomyelitis, a demyelinating disorder with neurologic and histopathologic characteristics similar to multiple sclerosis. Animals with experimental allergic encephalomyelitis received daily intraperitoneal injections of either preservative-free saline (group 1), catalase (group 2), or glutathione peroxidase (group 3) for 2.2 months after the onset of appendicular paralysis. Following intravascular administration, extravascular leakage of horseradish peroxidase was histopathologically graded as mild, moderate, or severe within the optic nerve head and myelinated retrolaminar nerve. Severe extravasation of horseradish peroxidase was exclusive to group 1, in addition to moderate and mild leakage. In groups 2 and 3, leakage of horseradish peroxidase was infrequent, and when detected, it was graded as mild. Detoxification of hydrogen peroxide with catalase and glutathione peroxidase substantially reduced horseradish peroxidase leakage in experimental optic neuritis, suggesting a role for hydrogen peroxide and its reactive by-products in the pathogenesis of increased vascular permeability of the blood-brain barrier in experimental allergic encephalomyelitis.

Antioxidant enzyme suppression of demyelination in experimental optic neuritis.

Detoxification of hydrogen peroxide by the antioxidant enzyme catalase suppressed the neurologic manifestations of acute experimental allergic encephalomyelitis (EAE) and prevented death of treated adult strain-13 guinea pigs. The oxygen radical scavenger superoxide dismutase (SOD) delayed the onset of paralysis by one day, but did not prevent death from encephalomyelitis common to most of this group and all untreated animals. Histopathologic analysis of the optic nerves confirmed a statistically significant reduction in demyelination with catalase treatment, but not with SOD. Hydrogen peroxide, and/or its conversion products, discharged by phagocytic mononuclear cells, may play a role in the pathogenesis of demyelination in experimental optic neuritis.

Adult-onset macular degeneration in the Cayo Santiago macaques.

Since 1985 a group from the University of Florida has examined 136 rhesus monkeys from the Cayo Santiago colony. From the sample, 97 are older than nine years (approximately 30 human years) and 39 are younger. Drusen were found in 17% of the younger eyes and in 46% of the older eyes. All animals over 25 years of age had drusen in the central fundus. The incidence of drusen varied from 19-77% between five social groups. Incidence reported in random-source colonies in the continental U.S.A. is about six percent. Compared to near-age matched controls without drusen, selected rhesus exhibited visual resolution losses amounting to two Snellen-lines or more. The end-stage disciform changes and ultrastructural similarities are comparable with human macular disease. Future prospective studies may include therapies, surgical intervention, environmental manipulation and genetic research.

Macular disease in related rhesus monkeys.

During (January) 1986-(May) 1988, we examined 272 eyes in 136 rhesus monkeys in the closed Cayo Santiago colony of the Caribbean Primate Research Center of the University of Puerto Rico. Seventy-eight eyes were less than 10 years of age. One hundred and ninety-four were aged 10-28 years. The fundi were examined and photographed. Fluorescein angiography was performed in some eyes. Selected cases were evaluated for 'acuity' loss by recording of pattern-evoked retinal and cortical signals. Light and electron microscopy were used to evaluate the pigment epithelium of some animals. Thirty-eight percent of all eyes had posterior pole drusen. Incidence was highly age-related. When late-stage lesions were found, we did not see neovascularization, but late hyperfluorescence was consistent with degenerative scarring and atrophy. Electrophysiology demonstrated moderately reduced acuity in the presence of numerous macular drusen. Electrooculograms were low normal. Histopathology showed changes identical to those reported in human age-related macular degeneration. No eyes less than 10 years of age had confluent drusen or disciform-like lesions. The incidence of drusen in samples of some social groups was much higher than others.

Quantitative analysis of labelled inner retinal proteins in experimental optic neuritis.

In order to determine if axonal transport changes in chronic experimental allergic encephalomyelitis (EAE) were due to blockade or increased discharge of fast transported proteins from the inner retina, we examined the presence of pulse labeled proteins in autoradiograms of the optic nerve head, retinal ganglion cell and nerve fiber layers of juvenile strain-13 guinea pigs with chronic EAE and normal controls. Quantitative analysis of silver grains, performed six and twenty-four hours following the intravitreal injection of tritiated leucine, showed a decrease in inner retinal radioactivity in those with EAE, whereas no difference was detected between the two groups after three days. Grain counts within the optic nerve heads of guinea pigs with EAE were reduced at all time intervals studied. These results are consistent with an increase in discharge of fast transported proteins from retinal ganglion cells into optic nerve axons and support our previous observations of increased radioactivity at the foci of optic nerve demyelination.

Axonal transport reductions in acute experimental allergic encephalomyelitis: qualitative analysis of the optic nerve.

In order to determine if changes in axonal transport were different in adult animals with acute experimental allergic encephalomyelitis (EAE), in comparison to juvenile animals with chronic EAE, the effects of this acute demyelinating disorder on axonal transport were examined in the optic nerves of adult strain-13 guinea pigs. Utilizing autoradiographic analysis of silver grain counts, both the fast and slow components of orthograde transport were studied at intervals of thirty minutes, three hours, one day and three days after tritiated leucine injection into the vitreous cavity. In order to determine the contribution of fiber loss in acute EAE, optic nerve fiber density was analyzed from electron micrographs of normal and demyelinated nerves. Animals with acute EAE had a decrease in radioactivity at the lamina retinalis and lamina choroidalis after thirty minutes and three hours, and at the lamina scleralis and foci of demyelination after one and three days. A 16% loss of fibers did not account for as much as a 74% reduction in radioactivity with acute EAE. The global reductions in axonal transport observed in acute EAE animals may contribute to their progressive deterioration and eventual demise by lack of delivery of tubulo-vesicular materials for synaptic transmission, axolemmal proteins for electrogenesis and neurofilamentary components of the cytoskeleton. Moreover, they are unlike the increase of fast axonal transport associated with recovery of physiologic function characteristic of animals with the chronic form of the disease.

Very large neurons of the inner retina of humans and other mammals.

Large ganglion cells, called parasol cells, are known to occur in the Golgi-stained, human retina. This report describes a population of much larger cells that is not stained by Golgi technique. These cells may be located in the human ganglion cell layer using Nomarski differential interference contrast optics and unstained, flatmounted tissue. These cells are regularly distributed in young and old adults in a Gaussian fashion along the radii that extend from the perimacula toward the far periphery. The author did not find the cells in the central retina. The most frequent (J-type) cells have soma diameters between 26 and 40 microns. Rare (S-type) cells measure up to 55 microns in diameter. Many cells have processes that appear to be axons or dendrites. These cell types may be especially sensitive to damage early in diseases of the inner retina.

Division of the pattern-evoked retinal response by respiratory acidosis.

Analysis in the frequency domain divided the pattern-evoked retinal response (PERR) of the cat into two analog components. A mild respiratory acidosis was produced by raising the end-tidal CO2 from 4-6% to 12-14%. The onset of the acidosis (without hypoxia) was highly correlated with marked decreases in the low-frequency PERR component and in the b-wave of the flash-elicited ERG. The high-frequency PERR component was unchanged relative to the labile low-frequency component (p less than 0.01). The literature has established a firm link between local pH and Müller cell function. These data tend to confirm the hypothesis that the cat's PERR to some grating stimuli of less than 100% contrast may contain separable components of different cellular origin(s).

Tissue responses of the monkey retina: tuning and dependence on inner layer integrity.

Recent technical and conceptual advances have made it possible to experiment with models of local human inner retinal disease and changes in very small, tissue-specific signals. Local retrograde degeneration of the ganglion cells was induced in four rhesus monkeys by 160 degrees microdiathermy fiber layer burns at the nasal or temporal edges of the optic disc. There were no abnormalities of the classical electroretinograms (ERGs) during the following 210 days. With nasal lesions, pattern-evoked retinal (PERR) and cortical responses over a range of grating contrasts and spatial frequencies were largely normal. The authors found a cortical spatial tuning peak near 0.5 cycles/deg (cpd) and a retinal peak at 0.25-0.3 cpd. With temporal lesions, the retinal signals to high frequency stimuli (greater than 1.0 cpd) approached zero between 20-60 days. The cortical evoked signal declined with a course similar to the retinal components. Histological evidence was found for extensive loss of ganglion cells and fibers in a central 30-40 degrees temporal area, including the macula, 210 days after the temporal lesions. This is strong evidence that local ganglion cell-dependent electrical potentials, bearing little relation to the ERG, can be measured in response to selected stimuli.

Influence of antioxidant enzymes in reduction of optic disc edema in experimental optic neuritis.

Acute experimental allergic optic neuritis was induced in 18 adult strain-13 guinea pigs. The animals were divided into three groups. The first group of six animals received intraperitoneal injections of saline, the second group received superoxide dismutase (SOD), and the third group received catalase, given daily, starting 1 week after encephalogenic myelin sensitization. Morphometric analysis of longitudinal histopathologic sections of the optic nerve head revealed that the animals treated with the antioxidant enzyme catalase had a statistically significant reduction of optic disc edema when compared to the saline-treated group. Although animals treated with SOD had less optic disc swelling than the saline-treated controls, the differences were not statistically significant. These results indicate that detoxification of hydrogen peroxide, released by invading inflammatory cells, can reduce the severity of axonal swelling within the optic nerve head.

Night myopia.

Although the phenomenon of night myopia has been recognized for two centuries, its causes are still not fully understood. Early studies implicated spherical aberration and accommodation, but the degree to which either contributed was not clearly established. More recently, "laser speckle" techniques to measure myopia have allowed the collection of data on large subject populations and it appears that night myopia represents a tendency for accommodation to approximate the dark focus as low luminance levels degrade the clarity of the retinal image. In this article, the authors review the past and present literature on night myopia and related anomalous myopias, and describe techniques for their evaluation and correction.

Electrical response of bat retina to spectral stimulation: comparison of four microhiropteran species.

Electrical responses of the retinas of 4 species of microchiropteran bats stimulated by spectrally restricted light flashes were found to diverge systematically from the rhodopsin absorption spectrum. The divergence was progressively greater across the 4 species. The results appeared explainable by assuming a second photoreceptor class and photopigment which was present in progressively greater numbers in the retinas of Eptesicus fuscus, Desmodus rotundus, Artibeus jamaicensis and Carollia perspicillata.