Ophthalmology

Magnetic resonance imaging (MRI) requires patient immobility and children generally need to be sedated. The ideal sedative agent for functional MRI (fMRI) should only minimally hamper the neurophysiologic effect of the administered sensorial stimulation. This study compares the effect of propofol and midazolam on the fMRI auditory activation pattern in children. Fourteen children in the 3 to 7 year age group without neurologic or auditory deficits were randomly assigned to receive propofol or midazolam for sedation during auditory fMRI. Two patients in the midazolam group were excluded due to positive baseline MRIs. The children were stimulated using a passive listening task. The fMRI signal was modeled using various functions (hemodynamic response function, temporal derivative, and dispersion derivative) to check for the differing temporal characteristics of the signal between the groups. Patients in the propofol group showed activation only in the primary auditory cortex and exhibited a pattern more similar to that of nonsedated adults. Patients in the midazolam group exhibited a more complex pattern, presenting activation areas other than the primary auditory cortex; a delay in the functional response and higher duration variability were also observed. Our sample sizes are too small to derive a conclusive inference. Our preliminary study encourages the hypothesis that propofol is preferable to midazolam to maintain sedation in 3 to 7-yearold children during auditory fMRI because it facilitates the elicitation of a more focused auditory cortical activation pattern with less temporal and spatial dispersion.

The topographical distribution of relative sensitivity to red and green lights across the retina was assayed using a custom-made wide-field color multifocal electroretinogram apparatus. There were increases in the relative sensitivity to red compared to green light in the periphery that correlate with observed increases in the relative amount of long L! compared to middle~M! wavelength sensitive opsin mRNA. These results provide electrophysiological evidence that there is a dramatic increase in the ratio of L to M cones in the far periphery of the human retina. The central to far peripheral homogeneity in cone proportions has implications for understanding the developmental mechanisms that determine the identity of a cone as L or M and for understanding the circuitry for color vision in the peripheral retina.

Red-green colour blindness, which results from the absence of either the long-(L) or middle-(M) wavelength-sensitive visual photopigments, is the most common single locus genetic disorder. Here, the possibility of curing colour blindness using gene therapy was explored in experiments on adult monkeys that had been colour blind since birth. A third type of cone pigment was added to dichromatic retinas, providing the receptoral basis for trichromatic colour vision. This opened a new avenue to explore the requirements for establishing the neural circuits for a new dimension of colour sensation. Classic visual deprivation experiments1 have led to the expectation that neural connections established during development would not appropriately process an input that was not present from birth. Therefore, it was believed that treatment of congenital vision disorders would be ineffective unless administered to the very young. Here, however, addition of a third opsin in adult red-green colour-deficient primates was sufficient to produce trichromatic colour vision behaviour. Thus, trichromacy can arise from a single addition of a third cone class and it does not require an early developmental process. This provides a positive outlook for the potential of gene therapy to cure adult vision disorders.

The electroretinogram (ERG) provides information about outer retina function in both clinical and research applications. ERG components elicited by light increments and decrements can be separated using a long-flash paradigm in which periods of light ON and OFF are alternated. Here, the ON-OFF ERG is combined with a silent substitution technique to elicit responses from individual cone photoreceptor classes by modulating the intensities of three color lights between the two periods. The results focus on the short wavelength (S) cone pathways since they are vulnerable to disease and because there are many unanswered questions about S-cone ON and OFF circuitry.

In 1993, DeValois and DeValois proposed a 'multi-stage color model' to explain how the cortex is ultimately able to deconfound the responses of neurons receiving input from three cone types in order to produce separate red-green and blue-yellow systems, as well as segregate luminance percepts (black-white) from color. This model extended the biological implementation of Hurvich and Jameson's Opponent-Process Theory of color vision, a two-stage model encompassing the three cone types combined in a later opponent organization, which has been the accepted dogma in color vision. DeValois' model attempts to satisfy the long-remaining question of how the visual system separates luminance information from color, but what are the cellular mechanisms that establish the complicated neural wiring and higher-order operations required by the Multi-stage Model? During the last decade and a half, results from molecular biology have shed new light on the evolution of primate color v...

Red-green colour blindness, which results from the absence of either the long-(L) or middle-(M) wavelength-sensitive visual photopigments, is the most common single locus genetic disorder. Here, the possibility of curing colour blindness using gene therapy was explored in experiments on adult monkeys that had been colour blind since birth. A third type of cone pigment was added to dichromatic retinas, providing the receptoral basis for trichromatic colour vision. This opened a new avenue to explore the requirements for establishing the neural circuits for a new dimension of colour sensation. Classic visual deprivation experiments1 have led to the expectation that neural connections established during development would not appropriately process an input that was not present from birth. Therefore, it was believed that treatment of congenital vision disorders would be ineffective unless administered to the very young. Here, however, addition of a third opsin in adult red-green colour-deficient primates was sufficient to produce trichromatic colour vision behaviour. Thus, trichromacy can arise from a single addition of a third cone class and it does not require an early developmental process. This provides a positive outlook for the potential of gene therapy to cure adult vision disorders. Gene therapy was performed on adult squirrel monkeys (Saimiri sciureus) that were missing the L opsin gene. In this species, some females have trichromatic colour vision while males are red-green colour blind2. Serotype 2/5 recombinant adeno-associated virus (rAAV) containing a human L-opsin gene under control of the L/M opsin enhancer and promoter (Fig. 1a) was delivered to the photoreceptor layer via subretinal injections (see Full Methods online). Transcriptional regulatory elements were chosen to direct expression preferentially in M cones, but not short-(S) wavelength-sensitive cones or rods 3. To provide the receptoral basis for trichromacy, animals received three 100 μL injections (containing a total Users may view, print, copy, download and text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:

Midget retinal ganglion cells (RGCs) are the most common RGC type in the primate retina. Their responses have been proposed to mediate both color and spatial vision, yet the specific links between midget RGc responses and visual perception are unclear. previous research on the dual roles of midget RGCs has focused on those comparing long (L) vs. middle (M) wavelength sensitive cones. However, there is evidence for several other rare midget RGC subtypes receiving Scone input, but their role in color and spatial vision is uncertain. Here, we confirm the existence of the single Scone center OFF midget RGC circuit in the central retina of macaque monkey both structurally and functionally. We investigated the receptive field properties of the S-OFF midget circuit with single cell electrophysiology and 3D electron microscopy reconstructions of the upstream circuitry. Like the well-studied L vs. M midget RGCs, the S-OFF midget RGCs have a center-surround receptive field consistent with a role in spatial vision. While spectral opponency in a primate RGC is classically assumed to contribute to hue perception, a role supporting edge detection is more consistent with the S-OFF midget RGC receptive field structure and studies of hue perception.

To determine whether between-eye refractive and visual outcomes after same-session laser in situ keratomileusis (LASIK) surgery are correlated, and to determine whether suboptimal visual and refractive outcomes in one eye are predictive of poor results in the fellow eye. Observational case series. Retrospective chart review. A total of 484 eyes of 242 patients met inclusion criteria of having undergone same-day LASIK surgery and having 3-month refractive and visual acuity outcomes. Statistical comparisons of outcomes were performed, including between-eye Pearson correlation analysis and logistic regression models for predicting second-eye outcome. Main outcome measures were 1-month, 3-month, and 6-month uncorrected visual acuity and manifest refraction. Refractive outcomes at 1, 3, and 6 months between first (right) and second eyes were not found to be significantly different. No difference in uncorrected or best spectacle-corrected visual acuity was observed between first and second eyes Refractive outcomes of spherical equivalent, sphere, and cylinder and visual outcomes of uncorrected and best spectacle-corrected visual acuity were highly correlated between the two eyes. Analysis of cases with suboptimal outcomes (> or =1 diopter from intended correction or uncorrected acuity equal to or worse than 20/40) suggests that a poor refractive or visual outcome in the first eye increases the risk of a poor outcome in the second eye by approximately 20-fold. Retrospective analysis of refractive and visual outcomes from patients undergoing same-session bilateral LASIK demonstrates a high correlation of refractive and visual outcome between the eyes.

Mice lacking rods and cones retain pupillary light reflexes that are mediated by intrinsically photosensitive retinal ganglion cells (ipRGCs). Melanopsin is necessary and sufficient for this nonvisual photoreception. The mammalian inner retina also expresses the potential blue light photopigments cryptochromes 1 and 2. Previous studies have shown that outer retinal degenerate mice lacking cryptochromes have lower nonvisual photic sensitivity than retinal degenerate mice, suggesting a role for cryptochrome in inner retinal photoreception.

Retinitis pigmentosa (RP) and age-related macular degeneration (AMD) are blinding diseases caused by the degeneration of rods and cones, leaving the remainder of the visual system unable to respond to light. Here, we report a chemical photoswitch named DENAQ that restores retinal responses to white light of intensity similar to ordinary daylight. A single intraocular injection of DENAQ photosensitizes the blind retina for days, restoring electrophysiological and behavioral responses with no toxicity. Experiments on mouse strains with functional, nonfunctional, or degenerated rods and cones show that DENAQ is effective only in retinas with degenerated photoreceptors. DENAQ confers light sensitivity on a hyperpolarization-activated inward current that is enhanced in degenerated retina, enabling optical control of retinal ganglion cell firing. The acceptable light sensitivity, favorable spectral sensitivity, and selective targeting to diseased tissue make DENAQ a prime drug candidate for vision restoration in patients with end-stage RP and AMD.

We present here a case of a 9-year-old boy with bilateral anterior uveitis and an extremely elevated urinary β2-microglobulin level (25,400 μg/l). The normal range for urinary excretion of β2-microglobulin is 0-300 μg/l. In patients with tubulointerstitial nephritis and uveitis syndrome (TINU), elevations typically range from 1,260 to 5,160 μg/l. Renal biopsy was pursued, and significant granulomatous interstitial nephritis consistent with sarcoidosis was identified. Systemic immune modulation was required for control of ocular inflammation. This case highlights the importance of urinary β2-microglobulin testing in the pediatric patient uveitis population, and additionally the need to pursue kidney biopsy in the presence of extreme elevations in urinary β2-microglobulin to differentiate between TINU and sarcoidosis.

PURPOSE. To determine the relative contributions of inner and outer retinal photoreception to the pupillary light response. METHODS. Wild-type, retinal degenerate (rd/rd), and melanopsin mutant (opn4 Ϫ/Ϫ) mice were tested for pupillary light responsiveness by video pupillometry before, during, and after exposure to supersaturating light intensities. Similar lighting protocols were used to probe responses of intrinsically photosensitive retinal ganglion cells (ipRGCs) recorded with multielectrode arrays ex vivo. RESULTS. Both outer retinal photoreceptors (rods and cones) and inner retinal photoreceptors (intrinsically photosensitive retinal ganglion cells [ipRGCs]) are sufficient to drive the pupillary light response in mice. After supersaturating light exposure, rather than bleaching or adapting, rd/rd mice showed paradoxical potentiation of responses to subsaturating light exposure. opn4 Ϫ/Ϫ mice, in contrast, could not sustain pupillary constriction under continuous bright illumination, and showed desensitization after bright-light exposure. Both the intensity of light necessary to induce potentiation and the spectral sensitivity for sustained and potentiated responses differed from that necessary to trigger pupillary constriction, suggesting that photopotentiation is dependent on a pigmentstate distinct from that triggering the pupillary light response itself. Multielectrode array recordings of ipRGCs from rd/rd retinas demonstrated persistent cell firing under continuous light exposure but did not show potentiation. CONCLUSIONS. Unique photoreceptive properties of intrinsically photosensitive RGCs confer resistance to bleaching and/or adaptation under continuous bright illumination to the pupillary light response and suggest the presence of a photopigment with multiple absorption states.