Glen A. Gole

The Effect of Amblyopia on Fine Motor Skills in Children

PURPOSE In an investigation of the functional impact of amblyopia in children, the fine motor skills of amblyopes and age-matched control subjects were compared. The influence of visual factors that might predict any decrement in fine motor skills was also explored. METHODS Vision and fine motor skills were tested in a group of children (n = 82; mean age, 8.2 +/- 1.7 [SD] years) with amblyopia of different causes (infantile esotropia, n = 17; acquired strabismus, n = 28; anisometropia, n = 15; mixed, n = 13; and deprivation n = 9), and age-matched control children (n = 37; age 8.3 +/- 1.3 years). Visual motor control (VMC) and upper limb speed and dexterity (ULSD) items of the Bruininks-Oseretsky Test of Motor Proficiency were assessed, and logMAR visual acuity (VA) and Randot stereopsis were measured. Multiple regression models were used to identify the visual determinants of fine motor skills performance. RESULTS Amblyopes performed significantly poorer than control subjects on 9 of 16 fine motor skills subitems and for the overall age-standardized scores for both VMC and ULSD items (P < 0.05). The effects were most evident on timed tasks. The etiology of amblyopia and level of binocular function significantly affected fine motor skill performance on both items; however, when examined in a multiple regression model that took into account the intercorrelation between visual characteristics, poorer fine motor skills performance was associated with strabismus (F(1,75) = 5.428; P = 0.022), but not with the level of binocular function, refractive error, or visual acuity in either eye. CONCLUSIONS Fine motor skills were reduced in children with amblyopia, particularly those with strabismus, compared with control subjects. The deficits in motor performance were greatest on manual dexterity tasks requiring speed and accuracy.

Deficient responses from the lateral geniculate nucleus in humans with amblyopia

Amblyopia or lazy eye is the most common cause of uniocular blindness in adults. It is caused by a disruption to normal visual development as a consequence of unmatched inputs from the two eyes in early life, arising from a turned eye (strabismus), unequal refractive error (anisometropia) or form deprivation (e.g. cataract). Animal models based on extracellular recordings in anesthetized animals suggest that the earliest site of the anomaly in the primate visual pathway is the primary visual cortex (corresponding to the striate cortex, cytoarchitectonic area 17 and area V1), which is where inputs from the two eyes are first combined in an excitatory fashion, whereas more distal and monocular processing structures such as the retina and lateral geniculate nucleus (LGN) are normal. Using high‐field functional magnetic resonance imaging in a group of human adults with amblyopia, we demonstrate that functional deficits are first observable at a thalamic level, that of the LGN. Our results suggest the need to re‐evaluate the current models of amblyopia that are based on the assumption of a purely cortical dysfunction, as well as the role for the LGN in visual development.

Angiogenic factors and their assay: Activity of formyl methionyl leucyl phenylalanine, adenosine diphosphate, heparin, copper, and bovine endothelium stimulating factor

A number of chemically unrelated substances have been compared for their neovasculogenic activity by two different in vivo tests, and for their ability to induce cultured endothelial cell migration and proliferation. Formyl methionyl leucyl phenylalanine, copper ions, heparin, adenosine diphosphate, and low-molecular-weight bovine endothelium stimulating factor were all neovasculogenic by the corneal pocket assay. By the chorioallantoic membrane assay, copper ions and formyl methionyl leucyl phenylalanine were not detectably neovasculogenic. By the same assay it has been possible to demonstrate angiogenic activity in bovine endothelium stimulating factor that is distinguishable from copper ions. This bovine factor, in contrast to the other agents, induced marked endothelial cell migration and also proliferation and may belong to a special class of agents which represents direct acting angiogenic activity.

Macular and nerve fiber layer thickness in amblyopia: the Sydney Childhood Eye Study.

PURPOSE To examine macular and peripapillary retinal nerve fiber layer (RNFL) thickness in amblyopia. DESIGN Population-based cross-sectional study. PARTICIPANTS Of 4118 children examined in the Sydney Childhood Eye Study (incorporating the Sydney Myopia Study) from 34 randomly selected primary schools and 21 secondary schools from 2003 to 2005, 3529 (85.7%) were included in this analysis. The median age of the 2 samples was 6 years (n = 1395) and 12 years (n = 2134), respectively. METHODS A detailed eye examination was conducted on all children, including determination of best-corrected visual acuity (logarithm of the minimum angle of resolution [logMAR]), autorefraction (RK-F1 autorefractor, Canon, Tokyo, Japan) after cyclopentolate (1%), cover testing to identify strabismus, and optical coherence tomography (StratusOCT, Carl Zeiss Meditec, Dublin, CA) through dilated pupils to obtain macula and peripapillary RNFL thickness. Amblyopia was defined as best visual acuity <0.3 logMAR units not explained by any obvious underlying eye or visual pathway abnormalities. Anisometropia was defined as an interocular difference of at least 1.0 diopter of the spherical equivalent refraction. MAIN OUTCOME MEASURES Macular and peripapillary RNFL thickness. RESULTS Amblyopic eyes had slightly greater foveal minimum thickness than the normal fellow eye (by 5.0 microm; 95% confidence interval 0.1-9.9) and right eyes of non-amblyopic children (by approximately 10 microm), both P<0.05. This was more pronounced in 6-year-old children (6.9 microm) than 12-year-old children (4.2 microm). Amblyopic eyes also had slightly thicker central macula (1 mm diameter region) in both comparisons, although these differences were not statistically significant. The inner macular ring (outer radius 1.5 mm) was thinner in amblyopic than normal fellow eyes. Peripapillary RNFL thickness was not significantly different between amblyopic and normal fellow eyes or normal eyes of non-amblyopic children. CONCLUSIONS In children aged predominantly 6 and 12 years, central macular thickness may be increased in eyes with amblyopia, although it is uncertain if this precedes or follows the development of amblyopia. No differences in peripapillary RNFL thickness were found when compared with normal eyes. FINANCIAL DISCLOSURE(S) The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Are we there yet? Bevacizumab therapy for retinopathy of prematurity

The publication of the BEAT-ROP study of bevacizumab (Avastin) treatment for Zone I and II retinopathy of prematurity (ROP) has raised hopes that there might now be a simpler, cheaper and more effective treatment than laser therapy, the current standard of care. However, we would urge caution at this point in time. We review the scientific background to the use of intravitreal anti-vascular endothelial growth factor for ROP, highlight a number of design issues in the BEAT-ROP study and problems with interpretation of the results. For example, no visual outcomes were reported and the study was underpowered to assess longer term safety. Intravitreal bevacizumab leaks into the systemic circulation in animals and adult humans and there are real concerns of potential harm to the developing preterm infant because vascular growth factors play a critical role in organogenesis. We conclude that bevacizumab should be reserved for exceptional circumstances and compassionate use pending further studies. Laser remains the proven effective therapy for first line treatment of all forms of ROP with little systemic morbidity. Neonatology and ophthalmology have an impressive record of conducting collaborative multicentre studies and we urgently need further rigorously designed, adequately powered randomised trials of anti-VEGF agents that evaluate visual outcomes as well as short and long term ocular and systemic safety.

Epidemiology of open‐ and closed‐globe trauma presenting to Cairns Base Hospital, Queensland

Purpose:  To review the epidemiology of serious ocular trauma presenting to Cairns Base Hospital, from the far north Queensland health districts.

Retinopathy of Prematurity-Incidence Today

Retinopathy of prematurity (ROP) in high-income countries now occurs, mostly in extreme low birth weight infants. In those countries, the incidence of ROP seems to have declined incrementally over the last few decades. But in middle-income countries, high rates of premature birth and increasing resuscitation of premature infants, often with suboptimal standards of care, have resulted in a third epidemic of ROP. Improved maternal and neonatal care, ROP screening guidelines appropriate for middle-income countries, and widespread timely treatment are urgently called for to control this third epidemic.

Effect of amblyopia on self-esteem in children.

Purpose. In an investigation of the psychosocial impact of amblyopia on children, the perceived self-esteem of children who had been treated for amblyopia was compared with that of age-matched controls. The influence of amblyopia condition or treatment factors that may impact self-perception scores was also explored. Methods. Children with a history of treatment for amblyopia (n = 47; age 9.2 ± 1.3 years) and age-matched controls (n = 52; age 9.4 ± 0.5 years) completed a standardized age-appropriate questionnaire based evaluation of perceived self-esteem (Harter Self Perception Profile for Children). Their vision characteristics and treatment regimen were also recorded. Bivariate correlation analysis was used to investigate the amblyopic characteristics and treatment factors that may have influenced self-perception scores in the amblyopic group. Results. Children treated for amblyopia had significantly lower social acceptance scores than age-matched control children. In other areas related to self-esteem, including scholastic competence, physical appearance, athletic competence, behavioral conduct and global self worth, amblyopic children gave scores similar to those of control children. Within the amblyopic group, a lower social acceptance score was significantly correlated with a history of treatment with patching but not with a history of strabismus or wearing of glasses. Conclusions. Self-perception of social acceptance was lower in children treated for amblyopia compared with age-matched controls. A reduction in these scores was associated with a history of patching treatment but not with a history of strabismus or spectacle wear.

Selective inner retinal dysfunction precedes ganglion cell loss in a mouse glaucoma model

Background/aims: To correlate ganglion cell function with defined parameters of the elevated intraocular pressure profile (IOP) in a mouse glaucoma model and to determine the temporal relationship of these functional changes with ganglion cell death. Methods: Unilateral chronic ocular hypertension was induced in C57BL6/J mice by laser ablation of the limbal episcleral veins. Scotopic flash electroretinograms were recorded after 5, 10, 20, and 40 days to isolate specific outer and inner retinal responses. Inner retinal function was correlated with the pressure differential between treated and non-treated eyes at the time of electroretinographic recording, and with the cumulative IOP insult (the integral of the IOP.time profile). Peripheral and central ganglion cell densities were quantified by Brn-3 immunohistochemistry. Results: Elevated IOP induced a preferential deficit in inner retinal function. The positive scotopic threshold response (pSTR) was suppressed by 68% on day 5, by 50% on day 10, by 54% on day 20 and by 46% on day 40 after laser treatment. Inhibition of the STR correlated with the pressure differential between treated and non-treated eyes but not with the IOP.time integral. Inner retinal dysfunction preceded the progressive death of ganglion cells. Ganglion cell loss occurred preferentially in peripheral retina and correlated with the cumulative IOP insult. Conclusion: We have demonstrated specific inner retinal dysfunction in an inducible mouse glaucoma model. STRs are sensitive to elevated IOP per se, and their early suppression reflects ganglion cell dysfunction rather than cell death. The correlation between IOP elevation and suppression of inner retinal function, in the context of the temporal progression of ganglion cell death, suggests that a portion of the IOP-mediated ganglion cell dysfunction may be reversible.

The effects of acute intraocular pressure elevation on rat retinal glutamate transport.

Purpose:  To investigate the relationship between intraocular pressure (IOP), retinal glutamate transport and retinal hypoxia during acute IOP elevations of varying magnitude.