Identification of amblyogenic risk factors with the Brückner reflex test using the low-cost Arclight direct ophthalmoscope

Background/objectives The Arclight is a novel, low-cost, solar-powered direct ophthalmoscope developed for low resource settings as an alternative to more expensive, conventional devices. The Brückner reflex test (BRT) is a quick and effective means to screen for eye disease and amblyogenic risk factors. This test is however rarely performed in low resource settings due to the lack of access to ophthalmoscopes and trained health care workers. Our aim was to establish the sensitivity and specificity of the BRT when performed by a non-expert using an Arclight and compare to an expert as well as the results of a full clinic workup. Subjects/methods In this prospective, blinded study, 64 patients referred to a paediatric ophthalmology clinic had the BRT performed by a ‘non-expert’ observer (medical student) then an ‘expert’ observer (consultant ophthalmologist). These results were then compared against the ‘gold standard’ outcomes of a full clinical workup. Results BRT screening by the expert observer led to a sensitivity of 75.0% [95% CI: 57.9–86.8%] and a specificity of 90.6% [95% CI: 75.8–96.8%] in picking up media opacity, strabismus, refractive error or a combination of the above. For the non-expert, the sensitivity and specificity were 71.9% [95% CI: 54.6–84.4%] and 84.4% [95% CI: 68.3–93.1%], respectively. Conclusions The Arclight can be effectively used to perform the BRT and identify eye disease and common amblyogenic risk factors. Even when performed by a non-expert the results are highly specific and moderately sensitive. This study consequently offers support for the use of this low-cost ophthalmoscope in the expansion of eye screening by health care workers in low resource settings.PostprintPeer reviewe

Evidence of a retinotopic organization of early visual cortex but impaired extrastriate processing in sight recovery individuals

Numerous studies in visually deprived nonhuman animals have demonstrated sensitive periods for the functional development of the early visual cortex. However, in humans it is yet unknown which visual areas are shaped to which degree based on visual experience. The present study investigated the functional organization and processing capacities of early visual cortex in sight recovery individuals with either a history of congenital cataracts (CC) or late onset cataracts (developmental cataracts, DC). Visual event-related potentials (VERPs) were recorded to grating stimuli which were flashed in one of the four quadrants of the visual field. Participants had to detect rarely occurring grating orientations. The CC individuals showed the expected polarity reversal of the C1 wave between upper and lower visual field stimuli at the typical latency range. Since the C1 has been proposed to originate in the early retinotopic visual cortex, we concluded that one basic feature of the retinotopic organization, upper versus lower visual field organization, is spared in CC individuals. Group differences in the size and topography of the C1 effect, however, suggested a less precise functional tuning. The P1 wave, which has been associated with extrastriate visual cortex processing, was significantly attenuated in CC but not in DC individuals compared to typically sighted controls. The present study thus provides evidence for fundamental aspects of retinotopic processing in humans being independent of developmental vision. We suggest that visual impairments in sight recovery individuals may predominantly arise at higher cortical processing stages

An Unusual Combination of Neurological Manifestations and Sudden Vision Loss in a Child with Familial Hyperphosphatemic Tumoral Calcinosis

Hyperphosphatemia in the absence of renal failure is an unusual occurrence, particularly in children, but is a common primary feature of familial hyperphosphatemic tumor calcinosis. We report a child with hyperphosphatemia who presented with multiple episodes of neurologic dysfunction involving lower motor neuron facial nerve palsy along with sequential visual loss. He also had an episode of stroke. There was an extensive metastatic calcification of soft tissue and vasculature. Hyperphosphatemia with normal serum alkaline phosphatase, calcium, parathyroid hormone, and renal function was noted. He was managed with hemodialysis and sevelamer (3 months) without much success in reducing serum phosphate level, requiring continuous ambulatory peritoneal dialysis (3 years). Intact fibroblast growth factor 23 (FGF23) was undetectable, with C-terminal FGF23 fragments significantly elevated (2575 RU/ml, normal A (p.N162K) mutation in FGF23 exon 3, confirming the diagnoses of primary FGF23 deficiency, the first case to be reported from India

Abnormal Complement Activation and Inflammation in the Pathogenesis of Retinopathy of Prematurity

Retinopathy of prematurity (ROP) is a neurovascular complication in preterm babies, leading to severe visual impairment, but the underlying mechanisms are yet unclear. The present study aimed at unraveling the molecular mechanisms underlying the pathogenesis of ROP. A comprehensive screening of candidate genes in preterms with ROP (n = 189) and no-ROP (n = 167) was undertaken to identify variants conferring disease susceptibility. Allele and genotype frequencies, linkage disequilibrium and haplotypes were analyzed to identify the ROP-associated variants. Variants in CFH (p = 2.94 x 10(-7)), CFB (p = 1.71 x 10(-5)), FBLN5 (p = 9.2 x 10(-4)), CETP (p = 2.99 x 10(-5)), and CXCR4 (p = 1.32 x 10(-8)) genes exhibited significant associations with ROP. Further, a quantitative assessment of 27 candidate proteins and cytokines in the vitreous and tear samples of babies with severe ROP (n = 30) and congenital cataract (n = 30) was undertaken by multiplex bead arrays and further validated by western blotting and zymography. Significant elevation and activation of MMP9 (p = 0.038), CFH (p = 2.24 x 10(-5)), C3 (p = 0.05), C4 (p = 0.001), IL-1ra (p = 0.0019), vascular endothelial growth factor (VEGF) (p = 0.0027), and G-CSF (p = 0.0099) proteins were observed in the vitreous of ROP babies suggesting an increased inflammation under hypoxic condition. Along with inflammatory markers, activated macrophage/microglia were also detected in the vitreous of ROP babies that secreted complement component C3, VEGF, IL-1ra, and MMP-9 under hypoxic stress in a cell culture model. Increased expression of the inflammatory markers like the IL-1ra (p = 0.014), MMP2 (p = 0.0085), and MMP-9 (p = 0.03) in the tears of babies at different stages of ROP further demonstrated their potential role in disease progression. Based on these findings, we conclude that increased complement activation in the retina/vitreous in turn activated microglia leading to increased inflammation. A quantitative assessment of inflammatory markers in tears could help in early prediction of ROP progression and facilitate effective management of the disease, thereby preventing visual impairment

Effect of strabismus surgery on torticollis caused by congenital superior oblique palsy in young children

Purpose: To evaluate the outcome of strabismus surgery for congenital superior oblique palsy (SOP) in relation to correction of head tilt and hypertropia. The cohort of patients mainly involved very young children. This is the first study to use a standardized instrument to objectively measure torticollis before and after surgery. Materials and Methods: A non-comparative interventional case series of 13 cases of congenital superior oblique palsy with head tilt, who underwent simultaneous superior oblique tuck and inferior oblique recession between Jan 2000 and Dec 2008, were studied. Results: The mean duration of SOP until surgery was 36.8 months. Of the 12 unilateral cases, 8 were right-sided. Mean follow-up period was 17 months (range 7-36). The outcome was determined at the last follow-up. Mean pre-and post-operative hypertropia (p.d.) in forced primary position was 19 ± 7 and 2 ± 6, respectively ( P < 0.0001). The head tilt reduced from mean of 17 ± 9 to 2 ± 2 degrees ( P < 0.0001). Success, defined as hypertropia <5 PD and head tilt less than 5 degrees, was achieved in 69% (9/13. C.I. 42-88%) and 85% (11/13. C.I. 56-96%), respectively. The success rate for achieving both criteria was 61.5% (C.I. 35-88%). Five patients required additional surgery; usually a contralateral inferior rectus muscle recession, which was successful in all cases. One case developed asymptomatic Brown syndrome (7.69% - C.I. 6.7-22.2). Conclusions: Simultaneous superior oblique tuck and inferior oblique muscle recession can successfully treat selected cases of congenital superior oblique palsy. About one-third required an additional procedure, which led to total normalization of the head position