Quantitative fiber tracking of the optic radiation is correlated with visual-evoked potential amplitude in preterm infants.

BACKGROUND AND PURPOSE: Children born preterm are at risk for adverse outcome, including visual impairment. We examined the relationship between neonatal DTI and sVEP in children born preterm to determine whether visual outcomes are related to early measurements of brain microstructure. MATERIALS AND METHODS: Subjects were born at <34 weeks gestation and imaged before term-equivalent age. DTI fiber tracking was used to delineate the optic radiations and measure tract-specific average FA, D(av), and parallel and transverse diffusivity. Visual-evoked response amplitudes were measured as a function of spatial frequency, contrast, and vernier offset size with sVEP at 6-20 months after birth. The association between DTI and sVEP was assessed by using the Spearman correlation coefficient and linear regression for repeated measures. RESULTS: Nine children with 15 scans were included. The peak response amplitudes for spatial frequency sweeps were associated with increasing FA and decreasing D(av) and transverse diffusivity (P ≤ .006) but not with parallel diffusivity (P = 1). There was only modest association with the swept contrast condition and no detectable association with the vernier offset sweeps. CONCLUSIONS: Microstructure of the optic radiations measured shortly after birth is associated with quantitatively measured responses elicited by moderate-to-high contrast spatiotemporal gratings in infancy. These findings are in keeping with studies showing a relationship between brain microstructure and function. While the clinical impact is not known, quantitative neuroimaging of white matter may ultimately be important for predicting outcome in preterm neonates.

Ketamine anaesthesia for paediatric ophthalmology surgery.

AIMS: Children with treatable, vision impairing conditions may not have access to surgical care when they live in regions where anaesthesia is unavailable. The use of ketamine anaesthesia in a developing region was studied to determine its safety and effectiveness. METHODS: This is a consecutive series of 679 children who had a variety of paediatric eye disorders necessitating a short general anaesthesia. Ketamine was administered intravenously by a paediatrician with training in paediatric resuscitation procedures. Both intraocular and extraocular procedures were performed. The location of treatment was the Tilganga Eye Hospital in Kathmandu, Nepal, a developing region of the world. The study took place over a 5 year period. RESULTS: All procedures were performed without any anaesthetic complications. No child required unanticipated resuscitation or laryngeal intubation. Postoperative dysphoria occurred occasionally and was difficult to measure quantitatively. This side effect of ketamine resolved by the first postoperative day. CONCLUSION: Ketamine is an effective agent for both intraocular and extraocular surgery in the paediatric age group. None of the children in this series needed resuscitation or intubations, and the ophthalmic surgery was carried out safely. Ketamine can be used safely in any ophthalmic procedure of short duration by a person having some training in anaesthetic resuscitation procedures. Because of its simplicity and safety, ketamine may be useful in a simple ophthalmic setup in the developing word.

Tubedown-1 in remodeling of the developing vitreal vasculature in vivo and regulation of capillary outgrowth in vitro.

Tubedown-1 (tbdn-1) is a mammalian homologue of the N-terminal acetyltransferase subunit NAT1 of Saccharomyces cerevisiae and copurifies with an acetyltransferase activity. Tbdn-1 expression in endothelial cells becomes downregulated during the formation of capillary-like structures in vitro and is regulated in vivo in a manner which suggests a functional role in dampening blood vessel development. Here we show that tbdn-1 is expressed highly in the vitreal vascular network (tunica vasculosa lentis and vasa hyaloidea propria) during the pruning and remodeling phases of this transient structure. The vitreal blood vessels of mice harboring a targeted inactivation of TGF-beta2 fail to remodel and abnormally accumulate, a phenomenon reminiscent of the ocular pathology resembling persistent fetal vasculature (PFV) in humans. Since suppression of normal tbdn-1 expression has been previously observed in retinal vessel proliferation, we analyzed vitreal vascular changes and tbdn-1 expression in TGF-beta2(-/-) eyes. The nuclei of vitreal vessel endothelial cells in TGF-beta2(-/-) eyes express proliferating cell nuclear antigen (PCNA) and exhibit increased levels of active (P42/44)mitogen-activated protein kinase (phospho-(P42/44)MAPK), characteristics consistent with proliferative endothelial cells. In contrast to normal vitreal vessels, collagen IV expression exhibited a disorganized pattern in the TGF-beta2(-/-) vitreal vessels, suggesting vessel disorganization and possibly a breakdown of vessel basal laminae. Moreover, vitreal vessels of TGF-beta2(-/-) mice lack expression of pericyte markers (CD13, alpha smooth muscle actin) and show ultrastructural changes consistent with pericyte degeneration. The accumulating vitreal blood vessels of TGF-beta2(-/-) mice, while maintaining expression of the endothelial marker von Willebrand Factor, show a significant decrease in the expression of tbdn-1. We addressed the functional role of tbdn-1 in the regulation of vitreal blood vessels using an in vitro model of choroid-retina capillary outgrowth. Clones of the RF/6A fetal choroid-retina endothelial cell line showing suppression of tbdn-1 levels after overexpression of an antisense TBDN-1 cDNA display a significant increase in the formation of capillary-like structures in vitro compared with controls. These findings suggest that tbdn-1 inhibits capillary-like formation in vitro and may serve to dampen vitreal blood vessel formation preceding the regression of the vitreal vasculature during development. Our results also suggest that tbdn-1 may participate with TGF-beta2 in regulating normal development of the vitreal vasculature.

Retinopathy of prematurity.

The majority of cases of ROP regress spontaneously, but better treatment methods are needed to prevent retinal detachment and other effects of ROP such as myopia. In the future, molecular mechanisms may be exploited to treat ROP.

Suppressed expression of tubedown-1 in retinal neovascularization of proliferative diabetic retinopathy.

PURPOSE: Retinal neovascularization occurring as a complication of diabetes mellitus can cause vision loss and blindness. The identification and study of novel genes involved in retinal angiogenesis may define new targets to suppress retinal neovascularization in diabetes and other ocular diseases. A novel acetyltransferase subunit, tubedown-1 (tbdn-1), has been isolated, the expression of which is regulated during blood vessel development. Tbdn-1 is not detected in most adult vascular beds but persists at high levels in the adult ocular vasculature. The purpose of this study was to gain insight into the possible role of tbdn-1 in retinal blood vessels by characterizing its expression patterns in adult homeostasis and in retinal neovascularization associated with diabetes. METHODS: Western blot analysis and immunohistochemistry were performed to study the expression patterns of tbdn-1 during adult homeostasis in normal human retinas, in a model of choroid-retina endothelial capillary outgrowth in vitro, and in retinas showing neovascularization in patients with proliferative diabetic retinopathy (PDR). RESULTS: In adults during homeostasis, tbdn-1 was expressed highly in normal endothelium of retinal and limbic blood vessels. Tbdn-1 was also expressed in RF/6A, a rhesus macaque choroid-retina-derived endothelial cell line. In an in vitro model system using the RF/6A cell line, tbdn-1 expression was downregulated during the outgrowth of these cells into capillary-like structures on a reconstituted basement membrane matrix. Similar to this in vitro model, tbdn-1 expression is specifically suppressed in the endothelial cells of blood vessels and capillary fronds in vivo in both the neural retinal tissue and in preretinal membranes in eyes of patients with PDR. CONCLUSIONS: High levels of expression of tbdn-1 are associated with ocular endothelial homeostasis in adults. Conversely, low levels of tbdn-1 expression are associated with endothelial capillary outgrowth in vitro and retinal neovascularization in vivo. Because the tbdn-1 acetyltransferase subunit is a member of a family of regulatory enzymes that are known to control a range of processes, including cell growth and differentiation, through posttranslational modification, the current results support a hypothesis that tbdn-1 may be involved in maintaining homeostasis and preventing retinal neovascularization.

Development of a quantitative method to measure vision in children with chronic cortical visual impairment.

PURPOSE: Cortical visual impairment (CVI) is the most common cause of bilateral vision impairment in children in Western countries. Better quantitative tools for measuring vision are needed to assess these children, to allow measurement of their visual deficit, and to monitor their response to treatment and rehabilitation. The author performed a series of experiments to assess the use of the sweep visual evoked potential (VEP) as a quantitative tool for measuring vision in CVI. METHODS: The first experiment was a reliability measure (test/retest) of VEP grating acuity thresholds of 23 children with CVI. To validate the VEP procedure, VEP grating acuity was compared to a clinical measure of vision, the Huo scale, and to a psychophysical measure of vision, the Teller Acuity Card procedure. Finally, the sweep VEP was tested as a tool for defining optimal luminance conditions for grating acuity in 13 children with CVI, by measuring grating thresholds under 2 different luminance conditions: 50 and 100 candela per square meter (cd/m2). RESULTS: Retest thresholds were similar to original thresholds (r2 = 0.662; P = .003, 1-tailed t test). Grating VEP measures correlate significantly with the clinical index (r2 = 0.63; P = .00004). Teller acuity measurements are also similar to VEP measures in children (r2 = 0.64; P = .0005) but show lower acuities compared to the VEP for children with particularly low vision. Finally, 3 of 13 children tested under 2 background luminance conditions showed paradoxical improvement in grating threshold with dimmer luminance. CONCLUSIONS: The sweep VEP tool is a reliable and valid means for measuring grating acuity in children with CVI. The tool also shows promise as a means of determining the optimal visual environment for children with CVI.