Universal ocular screening of 481 infants using wide-field digital imaging system.

BACKGROUND: Universal ocular screening of infants is not a standard procedure in children's health care system in China. This pilot study investigated prevalence of ocular abnormalities of 6 weeks-age infants using wide-field digital imaging system. METHODS: Infants aged 6 weeks around were consecutively enrolled in a public hospital between April 2015 and August 2016. All the infants who were enrolled in the study underwent vision assessment, eye position examination, external eye check, pupillary light reflex, red reflex examination, anterior and posterior ocular segments were examined using flashlight, ophthalmoscope, and wide-field digital imaging system. RESULTS: A total of 481 infants at 45.1 ± 6.1 days after birth were enrolled in the study. 198 infants had abnormal findings (41.2%). Retinal white spots and retinal white areas were the most common findings (42.9% of abnormalities and 17.7% of all infants screened). The second major finding was retinal hemorrhage (16.2% of abnormalities and 6.7% of all infants screened). Other abnormal findings include retinal pigmentation, concomitant exotropia, neonatal dacryocystitis, retinopathy of prematurity, 'albinism-like fundus', congenital nasolacrimal duct obstruction, familial exudative vitreoretinopathy, immature retina, corneal dermoid tumor, large physiologic cupping of optic disc, congenital persistent pupillary membrane, entropion trichiasis, subconjunctival hemorrhage, congenital cataract, vitreous hemorrhage, ptosis and choroidal nevus. Intervention of any form was required in 22 infants, which accounted for 11.1% of abnormalities detected and 4.6% of all infants screened. CONCLUSION: Universal ocular screening is not only necessary for preterm infants but also for full-term infants. Addition of red reflex examination with wide-field digital imaging system can enhance the sensitivity of screening for ocular fundus abnormities. Further study with a long-term follow-up is needed in the future.

Nystagmus And Beyond: A Rare Ocular Motility Disorder.

Joubert syndrome is a rare autosomal recessive disorder predominantly involving the cerebellar vermis and brain stem. It is characterized clinically by global developmental delay, abnormal ocular movements, hypotonia, ataxia, intellectual disability and neonatal breathing abnormalities. Due to its uncommon and unconventional presentation, its diagnosis is usually delayed. Diagnosis of this atypical disease essentially relies upon the atypical finding of the "molar tooth" sign on Magnetic Resonance Imaging (MRI). We report a case of a 5-year-old boy who presented with abnormal eye movements, regression of milestones and developmental delay. MRI investigation revealed the distinctive molar tooth sign and bat wing shaped 4th ventricle. It requires high levels of clinical suspicion and holistic approach to such children who present with delayed milestones and abnormal eye movements, to reach at early detection and diagnosis of such rare pathologies.

Absence of associative motor learning and impaired time perception in a rare case of complete cerebellar agenesis.

Primary cerebellar agenesis (PCA), a brain disease where the cerebellum does not develop, is an extremely rare congenital disease with only eleven living cases reported thus far. Studies of the PCA case will thus provide valuable insights into the necessity of cerebellar development for controlling and modulating cognitive functions of the brain. In this follow-up study, we further investigated the performance of associative learning and time perception of a 26-year-old female complete PCA case. We assessed whether delayed eyeblink conditioning (EBC), which represents prototypical associative motor learning function of the cerebellum, could be partially compensated by the extracerebellar brain regions in complete absence of the cerebellum. We also assessed whether the cerebellum, a critical brain region for millisecond-range interval timing, is essential for perception of the second-range time interval. Twelve neurotypical age-matched individuals were used as controls. We found that although the complete PCA patient had only mild to moderate motor deficits, she was unable to perform the delayed EBC even after 1-week of extensive training. Additionally, the PCA patient also performed poorly during time reproduction experiments in which she overproduced the millisecond-range time intervals, while underproduced the second-range time intervals. The PCA patient also failed to perform the temporal eyeblink conditioning with a 5 s fixed interval as the conditioned stimulus. These results indicate that the cerebellum is indispensable for associative motor learning and involved in timing of sub-second intervals, as well as in the perception of second-range intervals.

Zebrafish retinal defects induced by ethanol exposure are rescued by retinoic acid and folic acid supplement.

Fetal Alcohol Spectrum Disorder (FASD) is caused by prenatal alcohol exposure, producing craniofacial, sensory, motor, and cognitive defects. FASD is highly prevalent in low socioeconomic populations, which are frequently accompanied by malnutrition. FASD-associated ocular pathologies include microphthalmia, optic nerve hypoplasia, and cataracts. The present study characterizes specific retinal tissue defects, identifies ethanol-sensitive stages during retinal development, and dissects the effect of nutrient supplements, such as retinoic acid (RA) and folic acid (FA) on ethanol-induced retinal defects. Exposure to pathophysiological concentrations of ethanol (during midblastula transition through somitogenesis; 2-24 h post fertilization [hpf]) altered critical transcription factor expression involved in retinal cell differentiation, and produced severe retinal ganglion cell, photoreceptor, and Müller glial differentiation defects. Ethanol exposure did not alter retinal cell differentiation induction, but increased retinal cell death and proliferation. RA and FA nutrient co-supplementation rescued retinal photoreceptor and ganglion cell differentiation defects. Ethanol exposure during retinal morphogenesis stages (16-24 hpf) produced retinal defects like those seen with ethanol exposure between 2 and 24 hpf. Significantly, during an ethanol-sensitive time window (16-24 hpf), RA co-supplementation moderately rescued these defects, whereas FA co-supplementation showed significant rescue of optic nerve and photoreceptor differentiation defects. Interestingly, RA, but not FA, supplementation after ethanol exposure could reverse ethanol-induced optic nerve and photoreceptor differentiation defects. Our results indicate that various ethanol-sensitive events underlie FASD-associated retinal defects. Nutrient supplements like retinoids and folate were effective in alleviating ethanol-induced retinal defects.

The temporal requirement for vitamin A in the developing eye: mechanism of action in optic fissure closure and new roles for the vitamin in regulating cell proliferation and adhesion in the embryonic retina.

Mammalian eye development requires vitamin A (retinol, ROL). The role of vitamin A at specific times during eye development was studied in rat fetuses made vitamin A deficient (VAD) after embryonic day (E) 10.5 (late VAD). The optic fissure does not close in late VAD embryos, and severe folding and collapse of the retina is observed at E18.5. Pitx2, a gene required for normal optic fissure closure, is dramatically downregulated in the periocular mesenchyme in late VAD embryos, and dissolution of the basal lamina does not occur at the optic fissure margin. The addition of ROL to late VAD embryos by E12.5 restores Pitx2 expression, supports dissolution of the basal lamina, and prevents coloboma, whereas supplementation at E13.5 does not. Surprisingly, ROL given as late as E13.5 completely prevents folding of the retina despite the presence of an open fetal fissure, showing that coloboma and retinal folding represent distinct VAD-dependent defects. Retinal folding due to VAD is preceded by an overall reduction in the percentage of cyclin D1 positive cells in the developing retina, (initially resulting in retinal thinning), as well as a dramatic reduction in the cell adhesion-related molecules, N-cadherin and beta-catenin. Reduction of retinal cell number combined with a loss of the normal cell-cell adhesion proteins may contribute to the collapse and folding of the retina that occurs in late VAD fetuses.

Essential role of Ca2+-binding protein 4, a Cav1.4 channel regulator, in photoreceptor synaptic function.

CaBP1-8 are neuronal Ca(2+)-binding proteins with similarity to calmodulin (CaM). Here we show that CaBP4 is specifically expressed in photoreceptors, where it is localized to synaptic terminals. The outer plexiform layer, which contains the photoreceptor synapses with secondary neurons, was thinner in the Cabp4(-/-) mice than in control mice. Cabp4(-/-) retinas also had ectopic synapses originating from rod bipolar and horizontal cells tha HJt extended into the outer nuclear layer. Responses of Cabp4(-/-) rod bipolars were reduced in sensitivity about 100-fold. Electroretinograms (ERGs) indicated a reduction in cone and rod synaptic function. The phenotype of Cabp4(-/-) mice shares similarities with that of incomplete congenital stationary night blindness (CSNB2) patients. CaBP4 directly associated with the C-terminal domain of the Ca(v)1.4 alpha(1)-subunit and shifted the activation of Ca(v)1.4 to hyperpolarized voltages in transfected cells. These observations indicate that CaBP4 is important for normal synaptic function, probably through regulation of Ca(2+) influx and neurotransmitter release in photoreceptor synaptic terminals.

Daily patterns of running wheel activity in male anophthalmic mice.

Circadian rhythms are generated by the suprachiasmatic nuclei (SCN) and synchronized (entrained) to environmental light-dark cycles by the retinohypothalamic tract (RHT), a direct pathway from the retina to the suprachiasmatic nuclei. In anophthalmic mice, the optic primordia are resorbed between embryonic days 11.5 and 13, before retinal ganglion cells emerge. Thus the retinohypothalamic tract, which is the primary "zeitgeber" for circadian rhythms in sighted animals, never forms, and there is no retinal or photic input to the circadian system. We have used wheel running activity, a highly consistent and reliable measure of circadian rhythmicity in rodents, to establish the properties of endogenous locomotor rhythms of anophthalmic mice. We have identified three subpopulations of anophthalmic mice: a) rhythmic with strong stable circadian period but significantly increased period length; b) rhythmic with unstable circadian period; and c) arrhythmic. Future correlation of locomotor rhythms with properties of the suprachiasmatic nuclei in these mice will clarify the relationship between generation and properties of circadian rhythms and the neuroanatomical, neurochemical, and molecular organization of the circadian clock.