Melanopsin-mediated amplification of cone signals in the human visual cortex.

The ambient daylight variation is coded by melanopsin photoreceptors and their luxotonic activity increases towards midday when colour temperatures are cooler, and irradiances are higher. Although melanopsin and cone photoresponses can be mediated via separate pathways, the connectivity of melanopsin cells across all levels of the retina enables them to modify cone signals. The downstream effects of melanopsin-cone interactions on human vision are however, incompletely understood. Here, we determined how the change in daytime melanopsin activation affects the human cone pathway signals in the visual cortex. A 5-primary silent-substitution method was developed to evaluate the dependence of cone-mediated signals on melanopsin activation by spectrally tuning the lights and stabilizing the rhodopsin activation under a constant cone photometric luminance. The retinal (white noise electroretinogram) and cortical responses (visual evoked potential) were simultaneously recorded with the photoreceptor-directed lights in 10 observers. By increasing the melanopsin activation, a reverse response pattern was observed with cone signals being supressed in the retina by 27% (p = 0.03) and subsequently amplified by 16% (p = 0.01) as they reach the cortex. We infer that melanopsin activity can amplify cone signals at sites distal to retinal bipolar cells to cause a decrease in the psychophysical Weber fraction for cone vision.

Protocol for isolation of melanopsin and rhodopsin in the human eye using silent substitution.

Melanopsin-mediated visual and non-visual functions are difficult to study in vivo. To isolate melanopsin responses, non-standard light stimulation instruments are required, with at least as many primaries as photoreceptor classes in the eye. In this protocol, we describe the physical light calibrations of the display instrumentation, control of stimulus artefacts, and correction of individual between-eye differences in human observers. The protocol achieves complete photoreceptor silent substitution in psychophysical, pupillometry, and electroretinographic experiments for probing melanopsin, rod, and cone function. For complete details on the use and execution of this protocol, please refer to Uprety et al. (2022).1.

Melanopsin photoreception differentially modulates rod-mediated and cone-mediated human temporal vision.

To evaluate the nature of interactions between visual pathways transmitting the slower melanopsin and faster rod and cone signals, we implement a temporal phase summation paradigm in human observers using photoreceptor-directed stimuli. We show that melanopsin stimulation interacts with and alters both rod-mediated and cone-mediated vision regardless of whether it is perceptually visible or not. Melanopsin-rod interactions result in either inhibitory or facilitatory summation depending on the temporal frequency and photoreceptor pathway contrast sensitivity. Moreover, by isolating rod vision, we reveal a bipartite intensity response property of the rod pathway in photopic lighting that extends its operational range at lower frequencies to beyond its classic saturation limits but at the expense of attenuating sensitivity at higher frequencies. In comparison, melanopsin-cone interactions always lead to facilitation. These interactions can be described by linear or probability summations and potentially involve multiple intraretinal and visual cortical pathways to set human visual contrast sensitivity.

Optimizing methods to isolate melanopsin-directed responses.

The intrinsic melanopsin photoresponse may initiate visual signals that differ in spatiotemporal characteristics from the cone-opsin- and rhodopsin-mediated signals. Applying the CIE standard observer functions in silent-substitution methods can require individual differences in photoreceptor spectral sensitivities and pre-receptoral filtering to be corrected; failure to do so can lead to the intrusion of more sensitive cone processes with putative melanopsin-directed stimuli. Here we evaluate heterochromatic flicker photometry (HFP) and photoreceptor-directed temporal white noise as techniques to limit the effect of these individual differences. Individualized luminous efficiency functions (V(λ)) were compared to the CIE standard observer functions. We show that adapting chromaticities used in silent-substitution methods can deviate by up to 54% in luminance when estimated with the individual and standard observer functions. These deviations lead to inadvertent cone intrusions in the visual functions measured with melanopsin-directed stimuli. To eliminate the intrusions, individual HFP corrections are sufficient at low frequencies (∼1Hz) but temporal white noise is also required at higher frequencies to desensitize penumbral cones. We therefore recommend the selective application of individualized observer calibration and/or temporal white noise in silent-substitution paradigms when studying melanopsin-directed photoresponses.

Refractive Status in Nepalese Pre-Term and Full-Term Infants Early in Life.

SIGNIFICANCE: This study suggests that pre-term infants, even without retinopathy of prematurity, are at risk for abnormal refractive development and informs the need for close monitoring of refractive error in such infants, regardless of their retinopathy of prematurity status. PURPOSE: The present study aims to investigate the refractive error trend in Nepalese pre-term infants without retinopathy of prematurity (ROP) in the first 6 months of life and explore the association of refractive error with birth weight (BW) and gestational age (GA). METHODS: Thirty-six pre-term infants without ROP and 40 full-term infants underwent cycloplegic retinoscopy at birth, term (for pre-term only), 3 months, and 6 months chronologically. Refractive status was classified into emmetropia (mean spherical equivalent refraction [SER] 0 to +3.00D), myopia (SER < 0.00D), and significant hyperopia (SER > +3.00D). Refractive parameters at various age points were compared between the pre-term and full-term infants using general linear model repeated measures ANOVA. RESULTS: At birth, the SER in the pre-term infants was +0.84 ± 1.72D; however, there was a shift toward myopia at 6 months of age (SER = -0.33 ± 1.95D). There was a significant difference in SER, astigmatism, and anisometropia between pre-term and full-term infants by 6 months of age (P < .01). Astigmatism and anisometropia showed an increasing trend with age in pre-term infants (P < .05 at 6 months) in contrast to a decreasing trend in full-term infants (P < 0.05 at 3 and 6 months). In pre-term infants, there was a statistically significant positive relationship between GA and SER (ß = 0.32, R = 17.6%, P < .05) but a negative relationship between BW and astigmatism (ß = -1.25, R = 20.6%, P < .01). CONCLUSIONS: Pre-term infants who do not develop ROP show a trend toward increasing myopia and demonstrate greater astigmatism and anisometropia than full-term infants in their first 6 months of life.

Profile of paediatric low vision population: a retrospective study from Nepal.

BACKGROUND: Childhood blindness and low vision have become major public health problems in developing countries. The purpose of this study was to categorise the causes of visual impairment according to aetiology and provide detailed local information on visually impaired children seeking low-vision services in a tertiary eye centre in Nepal. METHODS: A retrospective study was conducted of all visually impaired children (visual acuity of less than 6/18 in the better eye), aged less than 17 years seen in the low-vision clinic at the Sagarmatha Chaudhary Eye Hospital in Lahan between January 1, 2012 and December 31, 2013. RESULTS: Of the 558 visually impaired children, the majority were males, 356 (63.7 per cent). More than half (56.5 per cent) of the children were in the 11 to 16 years age group. Many of the low-vision children (52.9 per cent) were identified as having moderate visual impairment (visual acuity less than 6/18 to 6/60). Most children were diagnosed with childhood (36.2 per cent) or genetic (35.5 per cent) aetiology, followed by prenatal (22.2 per cent) and perinatal (6.1 per cent) aetiologies. Refractive error and amblyopia (20.1 per cent), retinitis pigmentosa (14.9 per cent) and macular dystrophy (13.4 per cent) were the most common causes of paediatric visual impairment. Nystagmus (50.0 per cent) was the most common cause of low vision in the one to five years age group, whereas refractive error and amblyopia were the major causes in the six to 10 and 11 to 16 years age group (17.6 and 22.9 per cent, respectively). Many of the children (86.0 per cent) were prescribed low-vision aids and 72.0 per cent of the low-vision aid users showed an improvement in visual acuity either at distance or near. CONCLUSION: Paediatric low vision has a negative impact on the quality of life in children. Data from this study indicate that knowledge about the local characteristics and aetiological categorisation of the causes of low vision are essential in tackling paediatric visual impairment. The findings also signify the importance of early intervention to ensure a better quality of life.