Ocular growth and metabolomics are dependent upon the spectral content of ambient white light.

Myopia results from an excessive axial growth of the eye, causing abnormal projection of remote images in front of the retina. Without adequate interventions, myopia is forecasted to affect 50% of the world population by 2050. Exposure to outdoor light plays a critical role in preventing myopia in children, possibly through the brightness and blue-shifted spectral composition of sunlight, which lacks in artificial indoor lighting. Here, we evaluated the impact of moderate levels of ambient standard white (SW: 233.1 lux, 3900 K) and blue-enriched white (BEW: 223.8 lux, 9700 K) lights on ocular growth and metabolomics in a chicken-model of form-deprivation myopia. Compared to SW light, BEW light decreased aberrant ocular axial elongation and accelerated recovery from form-deprivation. Furthermore, the metabolomic profiles in the vitreous and retinas of recovering form-deprived eyes were distinct from control eyes and were dependent on the spectral content of ambient light. For instance, exposure to BEW light was associated with deep lipid remodeling and metabolic changes related to energy production, cell proliferation, collagen turnover and nitric oxide metabolism. This study provides new insight on light-dependent modulations in ocular growth and metabolomics. If replicable in humans, our findings open new potential avenues for spectrally-tailored light-therapy strategies for myopia.

Light and myopia: from epidemiological studies to neurobiological mechanisms.

Myopia is far beyond its inconvenience and represents a true, highly prevalent, sight-threatening ocular condition, especially in Asia. Without adequate interventions, the current epidemic of myopia is projected to affect 50% of the world population by 2050, becoming the leading cause of irreversible blindness. Although blurred vision, the predominant symptom of myopia, can be improved by contact lenses, glasses or refractive surgery, corrected myopia, particularly high myopia, still carries the risk of secondary blinding complications such as glaucoma, myopic maculopathy and retinal detachment, prompting the need for prevention. Epidemiological studies have reported an association between outdoor time and myopia prevention in children. The protective effect of time spent outdoors could be due to the unique characteristics (intensity, spectral distribution, temporal pattern, etc.) of sunlight that are lacking in artificial lighting. Concomitantly, studies in animal models have highlighted the efficacy of light and its components in delaying or even stopping the development of myopia and endeavoured to elucidate possible mechanisms involved in this process. In this narrative review, we (1) summarize the current knowledge concerning light modulation of ocular growth and refractive error development based on studies in human and animal models, (2) summarize potential neurobiological mechanisms involved in the effects of light on ocular growth and emmetropization and (3) highlight a potential pathway for the translational development of noninvasive light-therapy strategies for myopia prevention in children.

Nicotinamide Deficiency in Primary Open-Angle Glaucoma.

Purpose: To investigate the plasma concentration of nicotinamide in primary open-angle glaucoma (POAG). Methods: Plasma of 34 POAG individuals was compared to that of 30 age- and sex-matched controls using a semiquantitative method based on liquid chromatography coupled to high-resolution mass spectrometry. Subsequently, an independent quantitative method, based on liquid chromatography coupled to mass spectrometry, was used to assess nicotinamide concentration in the plasma from the same initial cohort and from a replicative cohort of 20 POAG individuals and 15 controls. Results: Using the semiquantitative method, the plasma nicotinamide concentration was significantly lower in the initial cohort of POAG individuals compared to controls and further confirmed in the same cohort, using the targeted quantitative method, with mean concentrations of 0.14 µM (median: 0.12 µM; range, 0.06-0.28 µM) in the POAG group (-30%; P = 0.022) and 0.19 µM (median: 0.18 µM; range, 0.08-0.47 µM) in the control group. The quantitative dosage also disclosed a significantly lower plasma nicotinamide concentration (-33%; P = 0.011) in the replicative cohort with mean concentrations of 0.14 µM (median: 0.14 µM; range, 0.09-0.25 µM) in the POAG group, and 0.19 µM (median: 0.21 µM; range, 0.09-0.26 µM) in the control group. Conclusions: Glaucoma is associated with lower plasmatic nicotinamide levels, compared to controls, suggesting that nicotinamide supplementation might become a future therapeutic strategy. Further studies are needed, in larger cohorts, to confirm these preliminary findings.

Seeing the sound after visual loss: functional MRI in acquired auditory-visual synesthesia.

Acquired auditory-visual synesthesia (AVS) is a rare neurological sign, in which specific auditory stimulation triggers visual experience. In this study, we used event-related fMRI to explore the brain regions correlated with acquired monocular sound-induced phosphenes, which occurred 2 months after unilateral visual loss due to an ischemic optic neuropathy. During the fMRI session, 1-s pure tones at various pitches were presented to the patient, who was asked to report occurrence of sound-induced phosphenes by pressing one of the two buttons (yes/no). The brain activation during phosphene-experienced trials was contrasted with non-phosphene trials and compared to results obtained in one healthy control subject who underwent the same fMRI protocol. Our results suggest, for the first time, that acquired AVS occurring after visual impairment is associated with bilateral activation of primary and secondary visual cortex, possibly due to cross-wiring between auditory and visual sensory modalities.

Pupillary Responses to High-Irradiance Blue Light Correlate with Glaucoma Severity.

PURPOSE: To evaluate whether a chromatic pupillometry test can be used to detect impaired function of intrinsically photosensitive retinal ganglion cells (ipRGCs) in patients with primary open-angle glaucoma (POAG) and to determine if pupillary responses correlate with optic nerve damage and visual loss. DESIGN: Cross-sectional study. PARTICIPANTS: One hundred sixty-one healthy controls recruited from a community polyclinic (55 men; 151 ethnic Chinese) and 40 POAG patients recruited from a glaucoma clinic (22 men; 35 ethnic Chinese) 50 years of age or older. METHODS: Subjects underwent monocular exposure to narrowband blue light (469 nm) or red light (631 nm) using a modified Ganzfeld dome. Each light stimulus was increased gradually over 2 minutes to activate sequentially the rods, cones, and ipRGCs that mediate the pupillary light reflex. Pupil diameter was recorded using an infrared pupillography system. MAIN OUTCOME MEASURES: Pupillary responses to blue light and red light were compared between control subjects and those with POAG by constructing dose-response curves across a wide range of corneal irradiances (7-14 log photons/cm(2) per second). In patients with POAG, pupillary responses were evaluated relative to standard automated perimetry testing (Humphrey Visual Field [HVF]; Carl Zeiss Meditec, Dublin, CA) and scanning laser ophthalmoscopy parameters (Heidelberg Retinal Tomography [HRT]; Heidelberg Engineering, Heidelberg, Germany). RESULTS: The pupillary light reflex was reduced in patients with POAG only at higher irradiance levels, corresponding to the range of activation of ipRGCs. Pupillary responses to high-irradiance blue light associated more strongly with disease severity compared with responses to red light, with a significant linear correlation observed between pupil diameter and HVF mean deviation (r = -0.44; P = 0.005) as well as HRT linear cup-to-disc ratio (r = 0.61; P < 0.001) and several other optic nerve head parameters. CONCLUSIONS: In glaucomatous eyes, reduced pupillary responses to high-irradiance blue light were associated with greater visual field loss and optic disc cupping. In POAG, a short chromatic pupillometry test that evaluates the function of ipRGCs can be used to estimate the degree of damage to retinal ganglion cells that mediate image-forming vision. This approach could prove useful in detecting glaucoma.

Serum vitamin D status is associated with the presence but not the severity of primary open angle glaucoma.

OBJECTIVES: Vitamin D is involved in visual health and function. Our objective was to determine whether age-related vitamin D insufficiency was associated with the presence and the severity of primary open angle glaucoma (POAG) in a case-control study of older adults. STUDY DESIGN: Case-control study. MAIN OUTCOME MEASURES: One hundred fifty cases diagnosed with moderate-to-severe POAG (mean, 75.1 ± 8.5 years; 42.0% female) and 164 healthy controls (mean, 73.0 ± 7.9 years; 59.8% female) were included. POAG diagnosis was based on classical diagnostic criteria of optic nerve cupping and/or RNFL thinning, measured with optical coherence tomography. Severe POAG was defined as Humphrey visual field mean deviation (MD) worse than -12 dB. Vitamin D insufficiency was defined as serum 25OHD ≤ 75 nmol/L. Age, gender, mean arterial pressure, vitamin D supplementation, visual acuity, and intraocular pressure were used as potential confounders. RESULTS: POAG cases had lower mean serum 25OHD concentration than controls (42.9 ± 25.7 nmol/L versus 49.4 ± 29.5 nmol/L, P=0.039) and a greater prevalence of vitamin D insufficiency (90.7% versus 82.3%, P=0.032). Increased mean serum 25OHD concentrations were associated with lower POAG frequency, even after adjustment for potential confounders (OR=0.89 per 10 nmol/L of 25OHD, P=0.045). Similarly, vitamin D insufficiency was associated with POAG (OR=2.09, P=0.034). Among POAG cases, no 25OHD difference was observed between moderate and severe POAG cases (respectively, 39.2 ± 23.3 nmol/L versus 45.1 ± 26.7 nmol/L, P=0.188); and no between-group difference regarding the prevalence of vitamin D insufficiency (88.9% versus 94.0%, P=0.313). CONCLUSIONS: Decreased serum 25OHD concentration was associated with POAG. There was no 25OHD difference between moderate and severe POAG.

Melanopsin retinal ganglion cells are resistant to neurodegeneration in mitochondrial optic neuropathies.

Mitochondrial optic neuropathies, that is, Leber hereditary optic neuropathy and dominant optic atrophy, selectively affect retinal ganglion cells, causing visual loss with relatively preserved pupillary light reflex. The mammalian eye contains a light detection system based on a subset of retinal ganglion cells containing the photopigment melanopsin. These cells give origin to the retinohypothalamic tract and support the non-image-forming visual functions of the eye, which include the photoentrainment of circadian rhythms, light-induced suppression of melatonin secretion and pupillary light reflex. We studied the integrity of the retinohypothalamic tract in five patients with Leber hereditary optic neuropathy, in four with dominant optic atrophy and in nine controls by testing the light-induced suppression of nocturnal melatonin secretion. This response was maintained in optic neuropathy subjects as in controls, indicating that the retinohypothalamic tract is sufficiently preserved to drive light information detected by melanopsin retinal ganglion cells. We then investigated the histology of post-mortem eyes from two patients with Leber hereditary optic neuropathy and one case with dominant optic atrophy, compared with three age-matched controls. On these retinas, melanopsin retinal ganglion cells were characterized by immunohistochemistry and their number and distribution evaluated by a new protocol. In control retinas, we show that melanopsin retinal ganglion cells are lost with age and are more represented in the parafoveal region. In patients, we demonstrate a relative sparing of these cells compared with the massive loss of total retinal ganglion cells, even in the most affected areas of the retina. Our results demonstrate that melanopsin retinal ganglion cells resist neurodegeneration due to mitochondrial dysfunction and maintain non-image-forming functions of the eye in these visually impaired patients. We also show that in normal human retinas, these cells are more concentrated around the fovea and are lost with ageing. The current results provide a plausible explanation for the preservation of pupillary light reaction despite profound visual loss in patients with mitochondrial optic neuropathy, revealing the robustness of melanopsin retinal ganglion cells to a metabolic insult and opening the question of mechanisms that might protect these cells.