Mueller matrix retinal imager with optimized polarization conditions.

A new Mueller matrix polarimeter was used to image the retinas of normal subjects. Light from a linearly polarized 780 nm laser was passed through a system of variable retarders and scanned across the retina. Light returned from the eye passed through a second system of retarders and a polarizing beamsplitter to two confocal detection channels. Optimization of the polarimetric data reduction matrix was via a condition number metric. The accuracy and repeatability of polarization parameter measurements were within +/- 5%. The magnitudes and orientations of retardance and diattenuation, plus depolarization, were measured over 15 degrees of retina for 15 normal eyes.

Blue on yellow perimetry with scanning laser ophthalmoscopy in patients with age related macular disease.

BACKGROUND/AIM: The loss of short wavelength sensitive (SWS) cone mechanism sensitivity is related to severe vision loss in patients with age related maculopathy (ARM). A case-control study of patients with ARM and age matched controls was performed, using blue on yellow static perimetry. METHODS: A bright yellow background at 594 nm isolated the responses of short wavelength cone mechanisms to 458 nm targets. A scanning laser ophthalmoscope produced stimuli and provided real time, simultaneous fundus illumination. The macula was probed with 16 Goldmann IV targets, 1-10 degrees from fixation, using a staircase method. RESULTS: 24 patients with non-exudative ARM were matched to 24 subjects with normal fundus appearance. SWS cone pathway sensitivity for macular targets was significantly reduced in the patients with ARM compared to normals--15.45 (SD 4.56) dB v 17.22 (0.28) dB, respectively (p<0.0005). There was not only a diffuse loss of sensitivity in ARM patients, but also a localised loss of sensitivity over drusen (p<0.025). Neither the mean age, 69 (8) years, nor the mean visual acuity differed between groups, logMAR 0.09 (0.10) v 0.05 (0.06) for ARM patients v normals, respectively. Patients with soft drusen had lower sensitivity than those with hard drusen (p<0.05). CONCLUSION: A loss of SWS cone pathway sensitivity occurred in most patients with early ARM, despite good visual acuity, demonstrating a loss of visual function that cannot be attributed to ageing changes. The loss of sensitivity, despite good visual acuity, included both a diffuse loss and localised losses.

Angioscotometry with the scanning laser ophthalmoscope. Comparison of the effect of different wavelengths.

PURPOSE: Angioscotomas are scotomata caused by vessel shadows. Their extent may be influenced by physiological and pharmacologic conditions and disease. In this study, the authors quantified angioscotomas in normal subjects using a fundus perimetry technique with a scanning laser ophthalmoscope. They further investigated the influence of two different wavelengths on scotoma depth. METHODS: For blue-on-yellow perimetry, the authors used two different lasers--an argon laser (lambda = 458 nm) for stimuli and a low background and a HeNE (lambda = 594 nm) for a superimposed yellow background. For red-on-red perimetry, the authors used another HeNe laser (lambda = 633 nm). Fundus illumination was provided by an infrared light. Five healthy subjects were examined. Twenty-one to 24 stimuli (200 msec duration, 0.4 degree x 0.4 degree) were presented at different intensities in randomized order in a 5 degrees x 2.5 degrees retinal test field, directly inferior and adjacent to the disk. RESULTS: The depth of scotomas caused by major vessels varied in all subjects and depended on perimetry condition. To quantify the influence of vessels on sensitivity, the authors analyzed psychometric functions for stimuli projected on the vessels and for those far from the vessels. The authors found a significant difference for targets on the vessel compared to those far, which was more pronounced for the blue-on-yellow condition. CONCLUSIONS: Angioscotomas are detected better with blue targets on a yellow background than with red-on-red perimetry. The greater light absorption by hemoglobin and oxyhemoglobin at short wavelengths compared to longer wavelengths is not compensated for by visual mechanisms.

Foveal cone photopigment distribution: small alterations associated with macular pigment distribution.

PURPOSE: To map the photopigment distribution of central foveal cones in healthy adult subjects before potential onset of age-related macular degeneration. To compare alterations in cone photopigment distribution to those of macular pigment and examine those loci for subretinal changes. METHODS: Eleven healthy subjects (age range, 31-59 years) underwent reflectometry with a scanning laser ophthalmoscope. The difference in cone photopigment density in the fovea was mapped for the long-wavelength- and middle-wavelength-sensitive cones, using 594-nm light. Macular pigment was mapped with 488-nm and 514-nm light. Subretinal changes were investigated with infrared imaging (830-860 nm). RESULTS: Most subjects had small alterations in the regularity of their foveal cone photopigment distribution. Alterations were spatially related to macular pigment alterations but not to the presence of subretinal defects. Subjects were classified into three groups according to the type of alterations in the regularity of pigment distributions: central peak of photopigment and macular pigment, small foveal alterations, and broad distribution with missing central peak of photopigment or macular pigment. The resultant groups differed significantly in age, 43, 46, and 59 years, for groups 1, 2, and 3, respectively (P < 0.05). CONCLUSIONS: Small alterations in the distributions of foveal cone photopigment or macular pigment were found that varied among the subjects. Larger alterations in older subjects may indicate changes in foveal architecture with age, including potential vulnerability of central cones before the onset of clinically significant changes in the retinal pigment epithelium.

Quantification of cystoid changes in diabetic maculopathy.

PURPOSE: In patients with diabetic macular edema and cysts, quantification of the extent of the cystoid formation has been difficult. This study was performed to introduce reliable measurements of cysts, the quantification of the extent, and its relation to visual acuity. METHODS: Fluorescein angiography generated with a scanning laser ophthalmoscope provided detailed recognition not only of the foveal microvasculature, but also of well-demarcated cystoid formations in the early phases. The sampling area included the central 2.5 degrees of the fovea. Using digital image analysis, two independent observers estimated the area covered by cysts, the number of cysts, and the foveal avascular zone (FAZ). RESULTS: Twenty-three subjects with diabetes and macular cysts were enrolled in the current study. The mean area of the cysts was 0.315 +/- 0.241 mm2 (0.05 mm2 to 0.9 mm2), and the number of cysts ranged from 1 to 7. Both parameters, area of cysts (r2 = 0.61), and number of cysts (r2 = 0.48) showed a significant correlation with visual acuity (P < 0.01), whereas FAZ (0.08 to 0.58 mm2) showed no significant correlation with visual acuity. CONCLUSIONS: Fluorescein angiography allows a reproducible quantification of the extent of macular cysts. The relation of visual acuity to the number of cysts and to the area covered by the cystoid formation is highly significant. Thus, both these measures can provide an objective criterion for the estimation of visual prognosis and an outcome for evaluation therapy techniques.

A psychophysical technique for measuring cone photopigment bleaching.

A new, clinically applicable test has been developed to measure the bleaching of the foveal cone photopigments. This noninvasive test is called steady-state color matching. Steady-state color matching is based on the dependence of a color match on the optical density of the cone photopigments. By measuring the color match as a function of retinal illuminance, it is possible to compute the optical density of the cone photopigments at each illuminance. Thus, abnormalities of photopigment bleaching can be detected. This study demonstrates that the technique is readily performed by a clinical population. Patients with central serous retinopathy and retinitis pigmentosa are shown to have low effective optical densities.

Cone photopigment bleaching abnormalities in diabetes.

We have used a color-matching technique to obtain estimates of the optical density of cone photopigments as a function of retinal illuminance in patients with insulin-dependent diabetes mellitus (IDDM). We found that the half-bleach illuminance of some patients is abnormally high. That is, it takes more light to bleach an equivalent amount of photopigment in these patients. Since low illuminance color matches for these patients are normal, this implies that these patients have normal amounts of photopigment, but the photopigment is not bleaching normally. This result clearly points to abnormalities in the outer retina of these diabetic patients. The most likely causes of this abnormality are either decreases in the ability of the cones to absorb light, or an increased rate of regeneration of the cone photopigments.

Effects of flicker adaptation and temporal gain control on the flicker ERG.

The flicker electroretinogram (ERG) to stimuli varying in temporal frequency and modulation depth was recorded to investigate retinal gain control. With increasing modulation of a sinusoidal flickering stimulus, the flicker ERG shows an amplitude compression and a phase retardation (of the fundamental component) at 16 Hz, an amplitude expansion and a phase advance around 40-48 Hz, and an approximately linear response at 72 Hz. With sum-of-two-sinusoids stimuli, the second stimulus enhances the fundamental response to a 40 or 48 Hz test stimulus at low modulations, and reduces the variation in phase with modulation. This interaction depends primarily on the amplitude of the response to the second stimulus, but not its frequency. With temporally alternating stimuli, a similar but smaller interaction effect is measured. The results suggest that there is an active nonlinear gain control mechanism in the outer retina and this gain control works by adjusting the phase delay of the retinal response. The phase control mechanism is set by the amplitude of the outer retinal response integrated over time.

Foveal cone spacing and cone photopigment density difference: objective measurements in the same subjects.

Foveal cone spacing was measured in vivo using an objective technique: ocular speckle interferometry. Cone packing density was computed from cone spacing data. Foveal cone photopigment density difference was measured in the same subjects using retinal densitometry with a scanning laser ophthalmoscope. Both the cone packing density and cone photopigment density difference decreased sharply with increasing retinal eccentricity. From the comparison of both sets of measurements, the computed amounts of photopigment per cone increased slightly with increasing retinal eccentricity. Consistent with previous results, decreases in cone outer segment length are over-compensated by an increase in the outer segment area, at least in retinal eccentricities up to 1 deg.

Flicker brightness enhancement and visual nonlinearity.

The purpose of this study was to investigate the nonlinear mechanism underlying brightness enhancement, in which a flickering stimulus appears brighter than a steady stimulus of equal mean luminance. The flickering and matching stimuli were temporally alternated. Both were cosine windowed to minimize the potential effects of temporal transients. Subjects adjusted the amplitude of the matching stimulus to match it in brightness to the flickering stimulus. The temporal frequency, modulation, and waveform of the flickering stimulus were varied. With sinusoidal flicker, brightness enhancement increased with increasing modulation at all frequencies, peaking at about 16 Hz at full modulation. The results were modeled by a broad temporal filter followed by a single accelerating nonlinearity. The derived temporal sensitivity of the early filter inferred from brightness enhancement decreased more slowly at high frequencies than the filter(s) inferred from flicker modulation thresholds. With low frequency sawtooth flicker, brightness enhancement was phase-dependent at low, but not at high modulations, suggesting that multiple neural mechanisms may also be involved in addition to an early nonlinearity.

Short wavelength automated perimetry in age related maculopathy.

BACKGROUND/AIMS: Previous studies reported the predictive value of the short wavelength sensitive (SWS) cone mediated sensitivity for visual outcome in age related macular degeneration. In this study SWS sensitivity was measured by commercially available blue on yellow perimetry in patients with non-exudative age related maculopathy (ARM) and compared with the presence of morphological risk factors and the status of the fellow eye. METHODS: In a prospective cross sectional study, 126 patients (57 males, 69 females, mean age 71 (SD 6) years) with ARM (visual acuity >20/50) were tested. Central visual fields (blue on yellow) were obtained with a conventional perimeter. Fundus slides were graded by two independent observers for soft drusen and presence of focal hyperpigmentation. RESULTS: Mean sensitivity and standard deviation of all patients exhibited a significant reduction with age. Patients with soft drusen had significantly lower sensitivity than those without, whereas there were no differences in visual acuity (log MAR). Sensitivity was also reduced in those eyes with fellow eyes having a sight threatening complication of age related macular degeneration (AMD). Eyes with focal hyperpigmentation compared with those without had no loss of sensitivity, but did have a significant decrease in the central part of the field compared with the more eccentric. CONCLUSION: SWS sensitivity loss is associated with common risk factors for progression to AMD. Short wavelength automated perimetry is moderately rapid and readily available. It may serve as a tool in future ARM trials.

The Abney effect: chromaticity coordinates of unique and other constant hues.

We compared unique and other constant hue loci measured at a fixed retinal illuminance for the same observers. When expressed in Judd chromaticity coordinates, unique hue and constant hue data agreed. Unique blue loci were curved, and unique red and green loci were noncollinear. These data imply that unique hues are not a linear transformation of color matching functions. Linear models are only an approximation, even at a single luminance level.

Infrared imaging of sub-retinal structures in the human ocular fundus.

The interaction of infrared light with the human ocular fundus, particularly sub-retinal structures, was studied in vivo. Visible and infra-red wavelengths and a scanning laser ophthalmoscope were used to acquire digital images of the human fundus. The contrast and reflectance of selected retinal and sub-retinal features were computed for a series of wavelengths or modes of imaging. Near infrared light provides better visibility than visible light for sub-retinal features. Sub-retinal deposits appear light and thickened; the optic nerve head, retinal vessels, and choroidal vessels appear dark. Contrast and visibility of features increases with increasing wavelength from 795 to 895 nm. Optimizing the mode of imaging improves the visibility of some structures. This new quantitative basis for near infrared imaging techniques can be applied to a wide range of imaging modalities for the study of pathophysiology and treatment in diseases affecting the retinal pigment epithelium and Bruch's membrane, such as age-related macular degeneration.

Entoptic image quality of the retinal vasculature.

Spatial details of entoptically visible retinal vessels were investigated using transcleral and Maxwellian-view stimulators. Nine normal subjects provided detailed drawings of the entoptic images which were digitized and superimposed onto digitized fundus photographs and fluorescein angiograms from the same eyes. Subjects also used a tracing method to locate visible entoptic features. The trans-scleral method provided images similar in detail to standard fundus photography (lacking capillary detail, but capturing larger arteries, veins, arterioles and venules) in the macula and around the disk. The Maxwellian-view method illuminated the fovea (7.7 degree field) and provided foveola capillary detail (capillaries traversing the foveola, the capillary arcade forming the FAZ) as well as the larger foveal vessels supplying the foveola, and often contained more foveal detail that available with fluorescein angiography.

Small incision cataract surgery and placement of posterior chamber intraocular lenses in patients with diabetic retinopathy.

BACKGROUND AND OBJECTIVE: Diabetic patients undergoing cataract surgery have been demonstrated to have a guarded prognosis. Small incision cataract surgery has been postulated to cause fewer complications than other techniques of cataract extraction. We looked at small incision cataract surgery to see how diabetics fared. PATIENTS AND METHODS: One hundred fifty-four eyes of diabetic patients were evaluated preoperatively through dilated fundus examination and Snellen visual acuity. The eyes then underwent small incision cataract surgery and were followed, undergoing periodic ophthalmoscopy, Snellen visual acuity measurement and additional postoperative therapeutic and surgical intervention. RESULTS: Final visual acuity improved by two Snellen lines or more in 61 out of 154 (40%) eyes. Final visual acuity worsened in 38 out of 154 (25%) eyes. CONCLUSIONS: Our results are similar to those reported for extracapsular surgery and phacoemulsification, suggesting that the prognosis is guarded for diabetics, even when undergoing small incision cataract surgery.

Relationship between foveal birefringence and visual acuity in neovascular age-related macular degeneration.

PURPOSE: To investigate the relationship between visual acuity and foveal birefringence in patients with neovascular age-related macular degeneration. METHODS: In total, 40 patients with choroidal neovascularization underwent macular imaging with scanning laser polarimetry. Bowtie patterns, typically seen in birefringence images of the macula, were evaluated and classified into three categories: (1) regular bowtie present; (2) bowtie present, but disrupted; and (3) no bowtie present. The relation of the bowtie appearance to the best-corrected logMAR visual acuities was tested (ANOVA). RESULTS: Mean visual acuity was best for the group that had regular bowties (mean logMAR=0.34) and differed statistically significantly from the disrupted bowtie group and no bowtie group (P=0.01 and 0.0007). Ages for the three groups did not differ (P=0.31). CONCLUSIONS: Appearance of a regular bowtie indicates a substantially intact Henle fibre layer with the potential for good visual function, despite the presence of underlying pathology. Conversely, disruption or absence of a bowtie may indicate severe damage to the photoreceptors, consistent with the finding of poorer visual acuity.

Characteristics of exudative age-related macular degeneration determined in vivo with confocal and indirect infrared imaging.

PURPOSE: To evaluate the current and future interventions in age-related macular degeneration (AMD), it is essential to delineate the early clinical features associated with later visual loss. The authors describe the retinal pigment epithelium (RPE)/Bruch membrane region in ten patients with advance exudative AMD using current angiographic techniques and a noninvasive method: infrared (IR) imaging with the scanning laser ophthalmoscope. METHODS: Ten patients with exudative AMD, evidence by choroidal neovascularization (CNV), fibrovascular scar formation, pigment epithelial detachment, or serous subretinal fluid,were examined using IR imaging, fluorescein angiography, indocyanine green angiography, and stereoscopic viewing of fundus slides. The authors determined the number and size of drusen and subretinal deposits and the topographic character of the RPE/Bruch membrane area and of CNV. RESULTS: In all patients, IR imaging yielded the greatest number of drusen and subretinal deposits. Sheets of subretinal material, but few lesions consistent with soft drusen, were seen. Infrared imaging provided topographic information of evolving CNV. Choroidal neovascularization appeared as a complex with a dark central core, an enveloping reflective structure which created a halo-like appearance in the plane of focus, and outer retinal/subretinal striae. CONCLUSIONS: Infrared imaging provides a noninvasive, in vivo method to image early changes in the RPE/Bruch membrane. It offers advantages over current imaging techniques by minimizing light scatter through cloudy media and enhancing the ability to image through small pupils, retinal hyperpigmentation, blood, heavy exudation, or subretinal fluid. It provides additional information regarding early CNV, and the character of drusen and subretinal deposits.

Response of the retina at low temporal frequencies.

We investigated the low-frequency temporal response of the retina by measuring the corneal electroretinogram elicited by flickering lights. A sum of two temporal sine-wave modulations was used to generate difference frequencies between a 36-Hz standard stimulus and a series of low-frequency stimuli. The response of the retina at the difference frequency did not change as the low-frequency component of the stimulus was varied from 0.5 to 4 Hz. We also replicated an earlier study, stimulating the retina with a sum of two sine waves that were varied in average frequency but keeping the difference frequency constant. These data showed no change in the amplitude of the difference frequency as the average stimulus frequency was varied from 8 to almost 40 Hz. Taken together, the two sets of data support the notion that the in vivo early retinal response is low pass and extends without attenuation to frequencies greater than 30 Hz, in contrast to the sensitivity of the visual system measured by psychophysical techniques.

Color matching at high illuminances: photopigment optical density and pupil entry.

Changes in the effective optical density of the cones are sufficient to explain changes in color matches with retinal illuminance and pupil entry. We performed three experiments. In the first experiment, six observers made color matches under both bleached and unbleached conditions to a series of six standard wavelengths. The effects of bleaching could be modeled by a decrease in optical density of the L and M cone photopigments. Slight spectral shifts in the peak wavelengths of the photopigments were required for different observers. In the second experiment we varied retinal illuminance of the color-matching field from 2.4 to 5.4 log Td for a series of long-wavelength primaries. The shape of the color match versus the intensity function was unchanged by the wavelength composition of the matching field. In the third experiment we measured the change in color match with retinal illuminance for different pupil entry positions. At low luminances there was a marked dependence of the color match on pupil entry positions. At high illuminance there was only a small dependence. The half-bleach illuminance values varied as expected from the Stiles-Crawford I effect. We conclude that for wavelengths > 540 nm, changes in color matches with bleaching and pupil entry can be explained by changes in the effective optical density of the cones.