Normal optic nerve head topography in the early stages of dementia of the Alzheimer type.

In view of the existing controversy as to whether or not the optic nerve head (ONH) is altered in Alzheimer disease, we used modern imaging technology to evaluate the ONH structure in individuals with dementia of the Alzheimer type (DAT). Real-time topographical images of the ONH were obtained with a Heidelberg retina tomograph from individuals in the early stages of DAT and age-matched controls. The various ONH parameters examined in this study did not differ significantly between DAT and age-matched subjects. These results suggest that the deficits in visual function that are known to occur in DAT are not related to ONH structural anomalies, at least in the earlier stages of the disease.

Age-related changes in the flash electroretinogram and oscillatory potentials in individuals age 75 and older.

OBJECTIVES: To evaluate whether the inner plexiform layer of the retina is altered during senescence by examining the oscillatory potentials (OPs) of the flash electroretinogram (fERG) in individuals age 75 and older. DESIGN: Cross-sectional, observational study. SETTING: A university-based center. PARTICIPANTS: Fifty-six healthy volunteers (age 20-88 years). MEASUREMENTS: fERGs and OPs were first evaluated in scotopic conditions, following pupillary dilation and dark adaptation, in young (20-32 years; n = 30) and older (75-88 years; n = 26) individuals. Electrical signals were recorded with a Dawson-Trick-Litzkow type (DTL) fiber electrode in response to blue and white flashes. Red flashes were subsequently delivered to the test eye for photopic fERG and OP recordings following a period of light adaptation. RESULTS: The amplitude of the a- and b-waves in response to blue and white flashes was significantly decreased in older people and their implicit time was increased. The latency of the a- and b-waves under photopic conditions was also prolonged with senescence, but only the amplitude of the b-wave was reduced. The amplitude of most OPs recorded under both scotopic and photopic conditions decreased with age, whereas their implicit times were prolonged. CONCLUSIONS: Our results confirm previous findings regarding the age dependency of the fERG a- and b-waves. Furthermore, we provide novel information concerning the detrimental effects of age on the OPs, indicating that the neuronal elements within the inner plexiform layer of the retina are compromised with senescence.

Changes in the retinocortical evoked potentials in subjects 75 years of age and older.

OBJECTIVE: Current trends are showing a rapid increase in the elderly population, particularly the subgroup that is 75 years of age or more. Considering the fact that several ocular diseases are more prevalent among the elderly, it is increasingly important to investigate normal visual function in this subgroup of our population. The objective of this study was to determine the effects of advanced aging on visual retinocortical function by evaluating the electrophysiological responses of the most rapidly increasing segment of the geriatric population. METHODS: Fifty-eight healthy subjects between the ages of 20--32 years (n=30) and 75--88 years (n=28) participated in this study. We recorded their pattern electroretinograms (ERGs) and cortical visual evoked potentials (VEPs) under stimulus conditions biased toward the preferential response of the magnocellular and parvocellular subdivisions of the visual system. RESULTS: Elderly subjects showed reduced ERG amplitudes relative to young participants. The amplitude of the VEPs also decreased with age, while their latency increased. The effect of senescence was most apparent under stimulus conditions combining the magnocellular and parvocellular pathway contributions and less pronounced when the stimulus conditions were biased to favor the response of either system. CONCLUSIONS: Our results demonstrate that visual retinal and cortical function deteriorates with old age. Our data further indicate that senescence has widespread effects on the visual system, altering the functioning of both the magnocellular and parvocellular visual pathways.

Neuroretinal function is normal in early dementia of the Alzheimer type.

We recently demonstrated that retinal ganglion cell function, optic nerve head parameters and the retinal nerve fiber layer thickness are not altered in early dementia of the Alzheimer type (DAT). Our current objective was to assess whether the function of cells located more distally in the retina is also unaffected by the disease. We evaluated 23 individuals with early to moderate DAT and 23 healthy age-matched subjects, all displaying clinically normal visual function. Scotopic and photopic flash electroretinograms (fERGs) and oscillatory potentials (OPs) were recorded. The amplitude and latency of the retinal potentials did not differ between DAT and control subjects. Our current results showing normal fERGs and OPs in early DAT indicate that the underlying neurons giving rise to these signals are not impaired by the disease process. These data support and extend our recent findings suggesting that visual deficits in DAT do not stem from neuroretinal dysfunction.

Age-related topographical changes in the normal human optic nerve head measured by scanning laser tomography.

PURPOSE: This study was designed to investigate the effects of advanced aging on the optic nerve head (ONH) structure and retinal nerve fiber layer (RNFL) thickness in the eldest segment of our population. METHODS: Twenty-seven healthy elderly subjects between 75 and 88 years of age (average, 80.1 +/- 0.83 years) and 30 healthy younger subjects between 20 and 32 years of age (average, 23.1 +/- 0.50 years) were recruited for a cross-sectional comparison between ONH morphology and RNFL thickness as measured by scanning laser tomography. The ONH disc, cup, and rim areas; cup-to-disc ratio; and the mean thickness of the RNFL were quantified. RESULTS: The cup and disc areas as well as the cup-to-disc area ratio increased with age, whereas the RNFL thickness decreased during the course of normal senescence. CONCLUSIONS: Any diagnoses of ocular pathology in the elderly must differentiate the effects of normal aging on the ONH topography and RNFL thickness. To that effect, the present study provides a clinical profile of ocular structures that extend into the oldest geriatric age group.

An evaluation of the retinal nerve fiber layer thickness by scanning laser polarimetry in individuals with dementia of the Alzheimer type.

PURPOSE: To determine, using scanning laser polarimetry, whether or not the retinal nerve fiber layer (RNFL) is altered in dementia of the Alzheimer type (DAT). METHODS: Thirty individuals with mild to moderate DAT and 30 healthy age-matched controls participated in the study. Fundus images were acquired with a Nerve Fiber Analyzer. RNFL thickness measurements were obtained under an ellipse located 1.75 disc diameter from the optic nerve head (ONH) center. RESULTS: No differences in RNFL thickness were observed between DAT and healthy subjects. The regional distribution of RNFL thickness was similar between the two test groups, with the RNFL being thickest in the superior and inferior retinal segments relative to the nasal and temporal regions. CONCLUSIONS: Our data indicate that the RNFL is not altered in DAT, at least in the earlier stages of the disease.

Effects of oxygen and carbogen breathing on choroidal hemodynamics in humans.

PURPOSE: Previous studies in humans have demonstrated that oxygen (O2) reduces retinal vessel caliber and blood flow, whereas carbon dioxide (CO2) usually has opposite effects. The influence of O2 and CO2 on choroidal circulation is not fully understood, however. This study was conducted to determine the effects of systemic hyperoxia and hypercapnia on global choroidal hemodynamics, as evaluated by pulsatile ocular blood flow (POBF) tonography. METHODS: In this experiment, 16 and 22 healthy volunteers breathed 100% O2 and carbogen, respectively. POBF and intraocular pressure (IOP) were measured twice with a UK OBF tonograph for each of the following conditions: in ambient room air breathing, after breathing pure O2 or carbogen through a face mask, and in ambient room air 10 minutes after mask removal. Heart rate (HR), hemoglobin oxygen saturation level (SaO2), and systemic arterial blood pressure (BP) were monitored throughout testing. The end-tidal CO2 (EtCO2) level and respiratory rate (RR) were also recorded during carbogen breathing. RESULTS: Results revealed that HR was reduced (P<0.004) and SaO2 was increased (P = 0.0001) by both oxygen and carbogen breathing. Systemic arterial BP remained stable throughout the experiment. EtCO2 was increased during carbogen breathing (P = 0.0001), whereas RR was reduced (P = 0.0175). IOP was significantly decreased during both phases of the experiment (P = 0.0001). Finally, POBF was not altered by pure O2 breathing, but it increased on average by 7.7% during carbogen breathing (P = 0.0222). CONCLUSIONS: The data obtained with POBF tonography indicate that the choroid reacts to increased blood CO2 concentration, but not to systemic hyperoxia, in a manner similar to that in retinal and brain vessels.

Macular hemodynamic responses to short-term acute exercise in young healthy adults.

We investigated the effects of vigorous exercise on blood flow in the macular vasculature. The velocity and density of entoptically viewed leukocytes in the paramacular retinal capillaries were measured with an Oculix BFS-2000 blue field simulator in 18 healthy adults first at rest, and then after 20 min of exercise. Exercise typically increased the density of leukocytes with more variable effects on their velocity. When leukocyte velocity and density were factored together, macular blood flow increased only marginally after exercise. We conclude that retinal blood flow in the macula is subject to the influence of autoregulatory mechanisms presumably to sustain normal central visual function during increased systemic blood flow.

Using the POBF as an index of interocular blood flow effects during unilateral vascular stress.

Kergoat and Lovasik [(1994). Ophthalmic and Physiological Optics, 14, pp. 401-407] reported that a transient decrease in ocular perfusion pressure (OPP) decreased the neural function in the test eye but increased the responsivity in the contralateral untouched (control) eye. Here the hypothesis tested was that a transient unilateral vascular stress would induce an increase in the Pulsatile Ocular Blood Flow (POBF) in the opposite eye. The POBF was measured in 20 healthy volunteers with normal intraocular pressure (IOP) and brachial blood pressure (BP). The OPP was decreased in the test (right) eye by scleral suction, and a Langham OBF system was used to make four readings of the POBF for each eye for baseline conditions, and when the OPP was decreased in the test eye alone by 20 and 40% for a 2 min period. Each individual, as well as the group averaged data showed a progressive decrease in the POBF in the test eye during a stepwise reduction in the OPP. No change was found for the POBF for the control eyes. Within the limitations of the systems and testing procedures employed, it is concluded that unilateral alterations in the OPP do not cause a change in the POBF in the contralateral eye.

Correlating increased ocular and systemic blood pressures with neuroretinal function.

BACKGROUND: The microgravity environment of spaceflights alters the systemic circulation, decreasing the peripheral resistance, while increasing the heart rate and systemic blood pressure. HYPOTHESIS: Body orientation simulating fluid shifts associated with microgravity during spaceflights affects the neural retinal function. METHODS: Fifteen healthy adults between 18 and 26 yr of age participated in this study. Scotopic flash electroretinograms and oscillatory potentials were compared for: 1) baseline, wherein subjects were declined 30 degrees from vertical; and 2) for microgravity simulation where subjects were in a 7 degrees head down tilt for 90 min. RESULTS: Group averaged implicit times for the ERG b-wave, as well as OP3, OP4 and OP5 were prolonged after microgravity simulation, and the group averaged OP index was reduced. CONCLUSIONS: The results suggest that microgravity of relatively short duration may cause retinal ischemia manifest as neuroretinal dysfunction with yet undetermined effects on visual and overall performance.

Correlation of an exercise-induced increase in systemic circulation with neural retinal function in humans.

Although the effects of physical exertion on intraocular pressure and systemic blood pressure are well established, the retinal response to such physiologic stress has not been examined. We studied the effect of short-term intense exercise on the principal waves in the scotopic and photopic flash electroretinograms, as well as the lower-amplitude oscillatory potentials. Sixteen healthy volunteers between 20 and 30 years of age participated in this experiment. The electroretinograms and oscillatory potentials were recorded with a Nicolet CA-1000 clinical averager, using DTL-type fiber electrodes. All retinal potentials were taken immediately before and after a minimum 20-min period of stationary bicycling that increased the heart rate to about 140 beats per minute. The electroretinograms were recorded from eyes with dilated pupils, 10 min after white-light adaptation of the right eye, and 30 min after dark adaptation of the left eye. Red flashes and dim white flashes were used to elicit photopic and scotopic electroretinograms, respectively. While no changes were recorded for any of the electroretinogram components recorded under photopic conditions, the amplitude of OP5 was decreased and the implicit time of OP4 was delayed after exercise for scotopic conditions. We concluded that exercise caused component-specific changes in the scotopic oscillatory potentials. Since it is well known that oscillatory potentials are vulnerable to ischemia, scotopic oscillatory potentials may be used as simple noninvasive indices of the reactivity of the retinal vascular autoregulatory system during exercise.

Response of parapapillary retinal vessels to exercise.

PURPOSE: Using blue field entoptoscopy, we have recently shown that blood flow in the paramacular capillaries remained constant after moderate exercise. In the present study, our objective was to identify a mechanism by which perfusion of an area populated by capillaries of invariable diameter can be maintained constant during exercise, which changes blood flow throughout the body. METHODS: Twelve healthy volunteers between 20 and 30 years of age participated in the present study. Color fundus slides centered on vessels within 1 disc diameter of the optic nerve head and synchronized with systole or diastole were taken while subjects rested, and after 20 min of stationary bicycling. High resolution measurements of vessel diameter were based on density plot profiles generated from magnified and digitized images of neighboring arteries and veins. RESULTS: Our results showed that the group-averaged diameter of arteries measured either in systole or diastole decreased after exercise, but the group-averaged diameter of veins did not differ from baseline. CONCLUSIONS: We interpret the constriction of parent arteries as an effective mechanism for gating the flow of blood to downstream vessels such as those perfusing the macular area.

Gravity-induced homeostatic reactions in the macular and choroidal vasculature of the human eye.

We quantified the changes in macular and choroidal blood flow during body inversion to elaborate their hemodynamic attributes and relate them to our previously reported effects of inversion on visual neural function. Ten healthy subjects took part in the study. The intraocular pressure (IOP) was altered through graded body tilts. Macular and choroidal pulsatile ocular blood flow (POBF) were measured with an Oculix BFS 2000 and a Langham OBF system, respectively. Body inversion caused a systematic decrease in the POBF for all subjects. Systematic changes in macular leukocyte velocity and density were also found with inversion. Six of ten subjects showed a reciprocal relationship between the leukocyte density and velocity as a function of body orientation, while parallel changes in the leukocyte density and velocity were seen during inversion for the remaining subjects. Our results may reflect individual strategies for autoregulation within the macular circulation and an absence of autoregulation in the pulsatile component of the choroidal circulation.

Unilateral ocular vascular stress in man and retinal responsivity in the contralateral eye.

Autoregulation (AR), the capacity of retinal vessels to maintain a constant flow of blood during alterations in vascular perfusion pressure, has been studied by a variety of techniques. Psychophysical and electrophysiological procedures have been used as indirect measurements of the effectiveness of AR for maintaining normal visual function during altered ocular perfusion pressure (OPP) in a single eye. However, there have been no studies in normal subjects which have investigated the responsivity of the contralateral eye while the fellow eye undergoes transient vascular stress. In the present study, the components of the bilaterally recorded scotopic flash electroretinogram (ERG) were used as objective indices of visual neural function during transiently altered OPP. The principal finding was that a decrease in the OPP for the test eye was associated with a reversible attenuation of the retinal responsivity in that eye, and a supranormal oscillatory potential index in the contralateral eye. The existence of a central control mechanism, triggered at the eye level, may be responsible for this contralateral neural phenomenon.

A novel noninvasive videographic method for quantifying changes in the chromaticity of the optic nerve head with changes in the intraocular pressure, pulsatile choroidal blood flow and visual neural function in humans.

Vision loss in glaucoma may be due to the compressive effects of the intraocular pressure (IOP) on the ganglion cell axons, impaired blood flow to the optic nerve, or some combination of these two factors. While reducing the IOP may preserve vision in patients with elevated IOP, not all patients experience longterm benefits from this therapeutic approach. The survival of ganglion cells may be more dependent upon the degree of vascular perfusion of the optic nerve head (ONH). In this report we present some preliminary data on a new noninvasive videographic technique for elaborating the capacity of the ONH vasculature to maintain perfusion constancy in the presence of transient elevations of the IOP and reductions of the ocular perfusion pressure (OPP). Shortterm, stepwise reductions of the OPP in the test eye of visually normal subjects (n = 5) systematically altered both the chromaticity (hue, saturation, brightness) of the ONH and the pulsatile ocular blood flow (POBF) in the choroid. Similar transient reductions in the OPP were seen to impair normal retinal physiology, as indicated by a significant attenuation of the bilateral pattern-reversal electroretinograms (pERGs) in visually normal subjects (n = 7). This technique was also used to reveal spontaneous rhythmical variations in the ONH chromaticity which were linked to the cardiac pulse rate. This so-called "chromatic pulse" of the ONH offers potential as a useful clinical index for evaluating the vascular perfusion of the ONH. The diagnostic and prognostic potential of dynamic digital imaging for the detection of abnormal hemodynamics in the ONH is discussed.

Comparison of noninvasive methods to derive the mean central retinal artery pressure in man.

PURPOSE: The pressure within the ophthalmic artery can be estimated by several noninvasive procedures based on measurements of the pressure either within the central retinal artery (CRA) or the brachial artery. In this study we compared 5 methods of deriving the mean pressure within the ophthalmic artery in 10 healthy volunteers 21 to 31 years of age. METHODS: The pressure within the ophthalmic artery was calculated from estimates of the systolic and diastolic pressures within the CRA derived by suction ophthalmodynamometry (s-ODM), compression ophthalmodynamometry (c-ODM), interpolation from scleral compression/intraocular pressure (IOP) conversion tables, and measurements of the brachial blood pressure (BP). RESULTS: Group average CRA pressure values varied significantly across techniques, with the largest difference among methods being about 15 mm Hg. CRA pressures derived by s-ODM or c-ODM and direct measurements of the IOP yielded statistically identical values. These latter values were significantly lower than CRA pressures estimated by either scleral compression/IOP conversion tables, or those predicted from brachial BP measurements with the arm held up alongside the head, both of which produced equivalent values. The highest estimates of CRA pressures were obtained when brachial BP values were derived with the arm in its normal anatomical position. CONCLUSION: The patency of the vascular network to the eye and subsequent perfusion of intraocular neural tissue essential to normal visual function can be evaluated by simple clinical procedures. Although all techniques to estimate the pressure in the ophthalmic artery are relatively simple to use, they do not all yield the same absolute values and consequently should be interpreted in this light when used for either clinical or research purposes.

Electroretinogram in unilateral vascular stress in nondiabetic and diabetic subjects.

PURPOSE: The oscillatory potentials (OP's) of the flash-elicited electroretinogram (ERG) are vulnerable to changes in retinal circulation such as occur in insulin-dependent diabetes mellitus (IDDM). In an earlier study it was shown that rod-isolated ERG's were more sensitive than cone-isolated ERG's to transient changes in the ocular perfusion pressure (OPP). In the present study, a comparison was made of the susceptibility of scotopic white, red, and blue flash OP's to transiently decreased perfusion in normals. Scotopic white flash OP's were then compared to those obtained in subjects with IDDM. METHODS: The OPP was decreased by 20 and 40% through scleral suction in 10 normotensive healthy volunteers, as well as in 11 young subjects with IDDM. RESULTS: The data indicate that white flash OP's include early cone and later rod contributions. Both red and blue OP's were more variable than white OP's. For white flash OP's, component-specific changes to decreased OPP were found. CONCLUSION: The overall OP response profiles for the diabetic subjects during a stepwise short-term decrease in the OPP did not differ from those for nondiabetic subjects. The results are discussed in relation to retinal vascular autoregulation (AR) and choroidal blood flow.

Electroretinographic results and ocular vascular perfusion in type 1 diabetes.

PURPOSE: Although functional changes in vision are known to occur before overt diabetic retinopathy, the relationship between (1) the degree and timing of any visual dysfunction and (2) the duration and control of diabetes remains poorly defined. The authors compared the ability of patients with insulin-dependent diabetes mellitus and nondiabetic subjects to sustain normal retinal function during transient physiologic stress. Such provocative testing may be clinically useful to show subclinical dysfunction. METHODS: Retinal function during altered ocular perfusion pressure (OPP) produced by body inversion and scleral suction was quantified by scotopic white-flash electroretinography (ERG) in 11 young volunteers with insulin-dependent diabetes mellitus but without significant retinopathy and a group of normal subjects. RESULTS: Baseline ERG a- and b-waves did not differ across test groups, but the a-wave implicit time was prolonged for diabetic patients. Furthermore, four of five oscillatory potentials (OP) in the diabetic patients were smaller than those in the nondiabetic subjects. Although the amplitude and implicit time of some OP in the diabetic patients were changed to a larger degree, the overall OP response profile did not differ widely from that for the nondiabetic subjects. Also, the a- and b-waves and the OP index for the test eye in diabetic and normal subjects did not differ, but the control eyes showed some differences in these parameters. CONCLUSIONS: Retinal function and vascular autoregulation in young diabetic patients without visible retinopathy did not differ from those in nondiabetic subjects; they were reduced in both groups by a short-term attenuation of the OPP.

Differential effects of compression and suction ophthalmodynamometry on the scotopic blue-flash electroretinogram.

Several studies have investigated the effect of elevated intraocular pressure with reduced ocular perfusion pressure on visual neural function by means of compression and suction ophthalmodynamometry. We compared the effects of nominally equivalent reductions in the ocular perfusion pressure induced by compression and suction ophthalmodynamometry retinal function as measured by flash electroretinography. Scotopic blue-flash electroretinograms were recorded in five subjects for baseline conditions; during a 40% reduction in the ocular perfusion pressure effected in a first test session by compression ophthalmodynamometry; and then in a second test session some 4 hours later by suction ophthalmodynamometry. Fifteen consecutive electroretinographic sets were recorded during scleral compression or suction, and also after compression or suction was removed. Compression and suction ophthalmodynamometry decreased the electroretinogram b-wave to different degrees; overall, the electroretinogram was attenuated more by compression than by suction ophthalmodynamometry. In the recovery phase, the group averaged b-wave quickly increased to exceed baseline after both scleral compression and suction. The trends for prolonged implicit times over the duration of the study were similar for compression and suction ophthalmodynamometry.

Improving the diagnostic power of electroretinography by transient alteration of the ocular perfusion pressure.

In this report we present the results of a series of studies focusing on the effects of transient changes in the ocular perfusion pressure (OPP) on retinal function in normals as assessed by the flash electroretinogram (ERG). A transient increase or decrease in the OPP affected by body inversion and compression/suction ophthalmodynamometry (ODM), respectively, is shown to affect differentially the b-wave of scotopic and photopic ERG's. However, under dark-adapted conditions, the cone component of the red flash ERG b-wave exhibited a vulnerability to decreased OPP which approached that seen for the b-wave of the scotopic blue flash ERG b-wave. Similar test procedures used to investigate the functional response of the inner plexiform layer during altered OPP revealed component-specific changes in white flash scotopic oscillatory potentials (OP's). The results of these provocative tests of retinal function offer new insights into basic retinal physiology and encouraging prospects for practical clinical diagnostic procedures with enhanced sensitivity and specificity for subclinical retinal disorders.