Macular pigment and lutein supplementation in retinitis pigmentosa and Usher syndrome.

PURPOSE: To determine macular pigment (MP) in patients with inherited retinal degeneration and the response of MP and vision to supplementation of lutein. METHODS: Patients with retinitis pigmentosa (RP) or Usher syndrome and normal subjects had MP optical density profiles measured with heterochromatic flicker photometry. Serum carotenoids, visual acuity, foveal sensitivity, and retinal thickness (by optical coherence tomography [OCT]) were quantified. The effects on MP and central vision of 6 months of lutein supplementation at 20 mg/d were determined. RESULTS: MP density in the patients as a group did not differ from normal. Among patients with lower MP, there was a higher percentage of females, smokers, and light-colored irides. Disease expression tended to be more severe in patients with lower MP. Inner retinal thickness by OCT correlated positively with MP density in the patients. After supplementation, all participants showed an increase in serum lutein. Only approximately half the patients showed a statistically significant increase in MP. Retinal nonresponders had slightly greater disease severity but were otherwise not distinguishable from responders. Central vision was unchanged after supplementation. CONCLUSIONS: Factors previously associated with lower or higher MP density in normal subjects showed similar associations in RP and Usher syndrome. In addition, MP in patients may be affected by stage of retinal disease, especially that leading to abnormal foveal architecture. MP could be augmented by supplemental lutein in many but not all patients. There was no change in central vision after 6 months of lutein supplementation, but long-term influences on the natural history of these retinal degenerations require further study.

Senescence of foveal and parafoveal cone sensitivities and their relations to macular pigment density.

Foveal and parafoveal increment thresholds were measured for 50 observers (12-88 years of age) under conditions that isolated retinal mechanisms dominated by short- (S-), middle- (M-), or long- (L-) wave-sensitive cones. Thresholds were obtained on the plateau of the threshold-versus-intensity function of each isolated mechanism and were referred to the retina by using individual measurements of ocular media and macular pigment density. Age-related increases in foveal thresholds, specified at the retina, were found for all three cone mechanisms. Parallel sensitivity losses for each cone mechanism were also observed at 4 degrees and 8 degrees in the temporal retina. A significant positive correlation was found between foveal macular pigment density and the S-cone, but not the M- and L-cone, log sensitivity difference (0 degrees-8 degrees) specified at the retina. This relation is expected from the hypothesis that the macular pigment protects the photoreceptors from senescent losses in sensitivity. However, because this result is independent of age, it is interpreted as being due to local gain changes resulting from differential filtering of incident light by the macular pigment between the fovea and the parafovea.

Effects of known variations in photopigments on L/M cone ratios estimated from luminous efficiency functions.

The extent to which known variations in photopigment lambda max and optical density may affect cone ratios estimated from the spectral luminous efficiency function (LEF) was examined. LEFs were generated using L- and M-cone fundamentals, one of which had been shifted in lambda max (+/- 1, 2, 4 or 6 nm) or varied in peak optical density (increased or decreased by 10, 25 or 50%). A curve-fitting program was then used to estimate the L/M cone ratios for the generated LEFs assuming standard L- and M-cone fundamentals. These modeling exercises indicate that L/M cone ratios estimated from LEFs are highly correlated with long-wave sensitivity and with known variations in L-cone lambda max. Variations in M-cone lambda max and photopigment optical density for both cone types are also correlated with L/M cone ratios, but have much less impact on the estimated ratios.

M- and L-cones in early infancy: I. VEP responses to receptor-isolating stimuli at 4- and 8-weeks of age.

A silent-substitution technique combined with measures of the visually-evoked potential (VEP) was used to determine whether M- and L-cones are functional in early infancy. Data were successfully collected from twenty six infants in response to three receptor-isolation conditions (rod, M- and L-cone isolation) and a luminance-modulation condition. The efficacy of the receptor-isolation conditions was first verified by measuring VEP responses from both dichromatic and color-normal adults to each of the receptor-isolation conditions. Both 4- and 8-week-old infants demonstrated VEP responses to the M- and L-cone isolating stimuli, though the amplitude of the the responses at 4-weeks were reduced compared to those at 8-weeks. These data suggest that the functioning of M- and L-cones can be differentiated as early as 4-weeks of age.

M- and L-cones in early infancy: II. Action spectra at 8 weeks of age.

Field sensitivities were measured under conditions of M- and L-cone isolation for seven infants (8-12 weeks-old) and two adults, using silent-substitution and the visually evoked potential (VEP). The efficacy of the receptor-isolation conditions were first verified by measuring psychophysical and VEP-derived action spectra from two color-normal adults under conditions of M- and L-cone isolation. M- and L-cone action spectra obtained from the two methods were found to be similar to the Smith and Pokorny M- and L-cone fundamentals, respectively. The VEP-derived action spectra obtained from infants and adults were well fit by the Smith and Pokorny M- and L-cone fundamentals. These data, in conjunction with our previous study, confirm that M- and L-cones are operating by 8 weeks and possibly as early as 4 weeks of age.

The area of complete scotopic spatial summation enlarges with age.

The maximal area of complete scotopic spatial summation (Ricco's area) was determined for 50 subjects ranging in age from 19 to 87 yr. Increment thresholds were measured for 10-ms, 520-nm circular test lights of varying diameters that were superimposed and concentric with a 10 degrees, 640-nm circular background. The test lights were imaged in Maxwellian view along the horizontal meridian, 6 degrees nasal from a foveal fixation point. The results demonstrate a statistically significant enlargement of Ricco's area with age. The average angular subtenses of Ricco's areas for the ten youngest (mean = 26 yr) and ten oldest (mean = 75 yr) observers were approximately 48 and 69 arc min, respectively. Model simulations based on a series of optical transfer functions of the eye and varying degrees of intraocular light scatter for younger and older observers show that preneural factors cannot account for these results. Therefore changes in neural mechanisms must be invoked to explain the enlargement in the size of Ricco's area under scotopic conditions.

M- and L-cones in early infancy: III. Comparison of genotypic and phenotypic markers of color vision in infants and adults.

Genetic analyses were performed on five male children (approximately 3 years), two suspect color-normals and three suspects for congenital color vision deficiencies. These classifications were based on visually-evoked potential (VEP) responses to M- and L-cone-isolating stimuli obtained in a previous study when each subject was either 4- or 8-weeks old. The present analyses were performed in a blind study to characterize the genotypes of these subjects. Four male adults with various color vision phenotypes were also tested as a control. DNA was isolated using a non-invasive technique followed by polymerase chain reaction (PCR) amplification and restriction enzyme analysis to examine the genomic DNA of each subject. The genetic analyses confirmed the VEP identification of two color defective infants, and were consistent with the diagnosis of two other infants as color normal. A third infant was predicted by VEP analysis to have a protan defect, but he did not have a gene array typically found in protan observers.

Sensitizing properties of spectral lights in 4-month-old human infants.

Previous studies of infant attention, learning, and memory have revealed that certain stimulus properties may increase an infant's arousal or excitation level, thereby increasing responsiveness and facilitating the encoding and processing of information. In a series of experiments aimed at identifying stimulus determinants of sensitization, we examined visual responses from 4-month-old infants to spectral lights. Habituation data were obtained from 92 full-term infants separated into one of five groups. Each group viewed either a broadband white light (correlated color temperature approximately 2800 K) or one of four different spectral lights (lambda d = 470, 510, 570, or 650 nm) approximately corresponding to the elemental hues blue, green, yellow and red, respectively, for adults with normal trichromatic vision. Stimuli were equated in luminous efficiency for a standard infant observer. Stimulus fixation was recorded for twelve 10-s presentations, each separated by 10-s interstimulus intervals (ISIs). The results show that mean fixation times to the red and green lights were significantly greater than those for the blue and white light. Mean fixation time for the yellow light was also reduced (significantly) compared to the red but not the green light. These results suggest that the chromatic properties of red and green spectral lights may be more sensitizing to infants than those of the blue, yellow, or white lights.

Spectral efficiency measured by heterochromatic flicker photometry is similar in human infants and adults.

Spectral efficiency functions based on heterochromatic flicker photometry (HFP) were measured for three adults and 42 infants using a rapid visually-evoked potential (VEP) method. A 5 degrees-diameter, broadband standard (0.6 cd/m2) was presented in square-wave counterphase (15 Hz) with one of 13 monochromatic lights (420-660 nm; 20 nm steps). The intensity of the monochromatic light was continuously varied while extracting the phase-locked VEP amplitude of the fundamental component. HFP functions measured psychophysically by the method of adjustment were also obtained for the adults. Adult HFP functions from the two methods were found to be essentially the same. Both of these functions were compared to Vos'-modified 2 degrees V(lambda) function and the 10 degrees CIEV(lambda) function. The mean adult data were slightly better fit to the 2 degrees V(lambda) function than to the 10 degrees CIEV(lambda) function, although there was an elevation in sensitivity at 420 and 440 nm. Infant HFP functions were similar to Vos' modified V(lambda) except for an elevation in efficiency at short wavelengths. The mean infant HFP function agreed better with the 10 degrees CIEV(lambda) function than Vos'-modified V(lambda) function, but infant sensitivity was elevated by 0.4 log units at 420 nm compared to the 10 degrees CIE observer. The elevation found at short wavelengths for both adults and infants is attributed to individual and age-related variation in the density of the ocular media, and to reduced macular pigment screening resulting from use of a 5 degrees field size.(ABSTRACT TRUNCATED AT 250 WORDS)