Rockefeller S.L. Young

Retinitis Pigmentosa: A Symposium on Terminology and Methods of Examination

This report represents a summary of opinions expressed at a meeting of specialists interested in retinitis pigmentosa (RP) and allied diseases, at which an attempt was made to define some minimum guidelines for ocular evaluation of these disorders. The term RP would be reserved for a group of hereditary disorders that diffusely involve photoreceptor and pigment epithelial function, and should not be used when a secondary cause is suspected. RP may be classified by genetic type (single cases without known affected relatives should be termed isolated or simplex), by the topography of retinal involvement, and by the severity of disease (to identify subtypes with mild or localized disease). Patients should have at least one comprehensive examination that conforms to basic standards, preferable early in the course of the disease. The visual field examination should use both a small and a large test light. Electroretinographic testing should (1) use a full-field stimulus, and (2) routinely document three independent responses (cone, rod, and mixed cone-rod). Patients should be identifiable for future study or therapeutic trials. They should be counseled about the disease and followed regularly. No specific therapy exists at present for most of these diseases, but optical and night vision aids are available. Sunglasses for outdoor use are recommended until more is known about whether long-term exposure to bright sunlight alters the course of these diseases.

Pupillary correlates of light-evoked melanopsin activity in humans

We investigated whether cones are the only photosensitive process mediating the photopic pupillary light reflex. New analyses were performed on previously published recordings, focusing on those evoked by the onset of photopically equated short- and long-wavelength stimuli. Comparisons between responses revealed contraction differences that slowly grew to a peak and gradually declined. The late contraction was associated with short wavelengths and appeared mostly at the higher stimulus intensities. We conclude that cones are not the only photoreception process mediating the photopic ON-reflex and infer that melanopsin is another. Melanopsin contributes to the steady-state pupil size in daylight illumination.

Transient and sustained components of the pupillary responses evoked by luminance and color

That the pupil reacts to changes in luminance and color, as well as to spatial features in the retinal image raises questions about whether phasic and tonic and/or color and luminance visual pathways project to the pretectal pupillomotor neurons. The present study compares pupillary responses evoked by heterochromatic and achromatic luminance increments to investigate whether the pupillary responses evoked by color and by luminance are independent of one another. Principal component analysis is used to examine the constituents of the pupil responses. The results support the belief that the visual input to the pupillomotor system is organized into phasic and tonic (but not necessarily independent color and luminance) pathways.

Evidence for genetic heterogeneity in X-linked congenital stationary night blindness

X-linked congenital stationary night blindness (CSNB) is a nonprogressive retinal disorder characterized by disturbed or absent night vision; its clinical features may also include myopia, nystagmus, and impaired visual acuity. X-linked CSNB is clinically heterogeneous, and it may also be genetically heterogeneous. We have studied 32 families with X-linked CSNB, including 11 families with the complete form of CSNB and 21 families with the incomplete form of CSNB, to identify genetic-recombination events that would refine the location of the disease genes. Critical recombination events in the set of families with complete CSNB have localized a disease gene to the region between DXS556 and DXS8083, in Xp11.4-p11.3. Critical recombination events in the set of families with incomplete CSNB have localized a disease gene to the region between DXS722 and DXS8023, in Xp11.23. Further analysis of the incomplete-CSNB families, by means of disease-associated-haplotype construction, identified 17 families, of apparent Mennonite ancestry, that share portions of an ancestral chromosome. Results of this analysis refined the location of the gene for incomplete CSNB to the region between DXS722 and DXS255, a distance of 1.2 Mb. Genetic and clinical analyses of this set of 32 families with X-linked CSNB, together with the family studies reported in the literature, strongly suggest that two loci, one for complete (CSNB1) and one for incomplete (CSNB2) X-linked CSNB, can account for all reported mapping information.

Pupil size and the ablation zone in laser refractive surgery: considerations based on geometric optics

Purpose: To determine whether the currently accepted method of selecting a minimum ablation zone size for refractive surgery based on dark‐adapted pupil diameter is substantiated by geometric optical analysis. Setting: Department of Ophthalmology and Visual Sciences, Texas Tech University Health Sciences Center, Lubbock, Texas, USA. Methods: An optical model of the anterior segment was developed to calculate the effective corneal refractive diameter (ECRD), which is the diameter of the area of cornea that refracts all incident light rays arising from objects along the line of sight though the physical pupil (PP). The concept of the entrance pupil (EP) was reexamined and developed, and the ECRD was calculated over a range of corneal curvatures (K), anterior chamber depths (ACDs), and EP sizes. The model was generalized to include oblique light rays. Calculations were performed using MatLab Optimization Toolbox® software (The MathWorks). Results: For a given EP size, the ECRD was significantly influenced by K and slightly influenced by ACD. For objects on the line of sight, the ECRD was smaller than the EP in all cases. Regarding rays from objects in the periphery, the ECRD expanded rapidly as the angle of oblique incidence increased. Conclusions: For objects on the line of sight, the ECRD is always smaller than the clinically measured pupil (EP) because the EP is substantially magnified relative to the PP. Ablation zones larger than the EP should, in theory, prevent scattered or defocused light rays from contributing to the foveal image. When considering objects in the periphery, the increase in ECRD is sufficiently rapid that current refractive procedures cannot stop scattered light from these objects from contributing to the retinal image.

Transient and sustained components of the pupil response evoked by achromatic spatial patterns

The present study provides new clues about visual processes underlying the human pupillary responses evoked by achromatic spatial patterns. The pupillary responses can be modeled as a combination of two processes, a temporally transient process which saturates with increasing contrast and a temporally sustained process which varies linearly with increasing grating contrast. The transient process has low-pass, whereas the sustained process has a middle band-pass spatial filter characteristic. the results support the hypothesis that the visual input to the pupillomotor nuclei is composed of phasic and tonic visual neurons that are functionally similar to those in the magno (M)- and parvo (P)- cellular layers in the lateral geniculate nucleus.

Nature of the pupillary responses evoked by chromatic flashes on a white background

Color flashes on a steady-white background are classically used to isolate the response of the chromatic (color-opponent), as opposed to achromatic (luminance), channel in psychophysical investigations. The present study shows that pupillary responses evoked by such stimuli behave as if they are composed of functionally separable components. One component has a temporally transient waveform and has an action spectrum that is similar to the spectral sensitivity curve of the psychophysical chromatic channel. The present study discusses the possibility that the pupillary response is mediated by phasic (M-like) neurons and/or by tonic (P-like) neurons.

S-cone contribution to pupillary responses evoked by chromatic flash offset.

On a green or red background, the action spectrum of the pupillary responses evoked following the offset of chromatic test flashes shows a prominent short-wavelength lobe and suggests the contribution from photoreceptors other than the previously inferred M- and L-cones (Kimura & Young, Vision Research (1996). 36, 1543-1550), most likely from S-cones. Systematic changes in the shape of the intensity versus amplitude functions with test wavelengths and in the shape of the short-wavelength lobe with response amplitude criteria suggest an antagonistic interaction involving the short- and longer-wavelength photoreceptors.

A chromatic-cancellation property of human pupillary responses

The pupil exhibits a response property somewhat analogous to perceptual red-green cancellation. Across a limited range of flash intensities near threshold, pupillary constrictions evoked by red flashes can be reduced, if not nulled, by the simultaneous addition of a green flash. The percentage of trials on which a stimulus-evoked response can be correctly discriminated from noise also falls to chance level as a green flash is added to the red flash. In terms of the quanta absorbed by L and M cones, the cancellation can be modelled as a function of magnitude of 0.65*L-M.

Effect of adaptation and wavelength on the power spectrum of human oscillatory potentials

Oscillatory potentials were recorded from four adult subjects under dark- and light-adapted conditions with photopically balanced red and blue flashes. The responses between 80 and 200 Hz were analyzed by means of a Fast Fourier transform program. The results show a robust change in the power - but not in the frequency composition - with the different stimulus conditions. We suggest that an analysis of the total power within this frequency band may provide a quantitative way of evaluating the duplex nature of the oscillatory potentials.