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Frisca F.,University of Melbourne | Sabbadini R.A.,LPATH | Sabbadini R.A.,San Diego State University | Goldshmit Y.,OBrien Institute | And 4 more authors.
International Review of Cell and Molecular Biology | Year: 2012

Lysophosphatidic acid (LPA) is a bioactive lipid that regulates a broad range of cellular effects in various cell types, leading to a variety of responses in tissues, including in the nervous system. LPA and its receptors are found in the nervous system, with different cellular and temporal profiles. Through its ability to target most cells of the nervous system and its induction of pleiotropic effects, LPA mediates events during neural development and adulthood. In this review, we summarize the current knowledge on the effects of LPA in the nervous system, during development and adulthood, and in various pathologies of the nervous system. We also explore potential LPA intervention strategies for anti-LPA therapeutics. © 2012 Elsevier Inc.

Phillipou A.,University of Melbourne | Douglas J.,La Trobe University | Krieser D.,Paediatric Emergency | Ayton L.,Center for Eye Research Australia | Abel L.,University of Melbourne
Developmental Medicine and Child Neurology | Year: 2014

Aim: The aim of this study was to determine whether volitional saccadic impairments are present in children with mild closed head injury (mCHI) and whether these deficits are predictive of ongoing cognitive impairment. Method: We analysed a sample of 26 children with mCHI (20 males, 6 females; mean age 13y 1mo, SD 2y) and 29 age-matched comparison children (20 males, 9 females; mean age 12y 2mo, SD 2y). Participants completed a battery of saccadic eye movement tasks and a set of computer-based cognitive tasks at three time points: within 2 weeks of mCHI, and at 3 months and 6 months. Results: The group with mCHI made fewer errors on the antisaccade task at the first time point and showed increased latencies on prosaccades, correct antisaccades, and corrected antisaccade errors at the third time point (6mo). The group with mCHI also showed poorer performance on the cognitive tasks assessing memory. Interpretation: Even very mild, uncomplicated mCHI in children may persistently affect aspects of executive control and visual processing. © 2013 Mac Keith Press.

Sandhu S.S.,Sunderland Eye Infirmary | Sandhu S.S.,Center for Eye Research Australia | Manvikar S.,Sunderland Eye Infirmary | Steel D.H.W.,Sunderland Eye Infirmary
Clinical Ophthalmology | Year: 2010

Background/aims: To evaluate retrospectively the clinical outcomes of patients presenting with submacular hemorrhage (SMH) secondary to neovascular age-related macular degeneration (nAMD), treated by vitrectomy, submacular tissue plasminogen activator (tPA) injection and pneumatic displacement of SMH with air followed by postoperative intravitreal ranibizumab (RZB). Methods: Patients with SMH and nAMD had 25-guage vitrectomy and subretinal tPA (12.5 micrograms/0.1 mL) with fluid/air exchange. Intravitreal RZB was administered postoperatively to patients eligible for National Health Service (NHS) funded treatment. Results: Of the total of 16 patients, 11 (68.7%) had complete displacement of SMH. The remaining five had residual SMH, mainly subretinal pigment epithelium in location. Three of the four patients who previously had a failed expansile gas pneumatic displacement were successfully displaced with vitrectomy surgery. At presentation 5/16 (31.3%) patients were eligible for NHS funded intravitreal RZB. This increased to 12 patients after the vitrectomy procedure (75.0%). At 6 months postoperatively all improved by ≥1 line. Ten of the 16 patients (63%) improved by ≥2 lines, with 10 of the 12 patients (83%) treated with RZB improving by ≥2 lines. Conclusion: Vitrectomy/subretinal tPA/air to displace SMH followed by intravitreal RZB injection can stabilize/improve vision in patients with nAMD. This technique displaces hemorrhage not displaced by attempted expansile gas techniques. © 2010 Sandhu et al.

Du Toit R.,Fred Hollows Foundation New Zealand | Palagyi A.,Fred Hollows Foundation New Zealand | Ramke J.,Fred Hollows Foundation New Zealand | Brian G.,Fred Hollows Foundation New Zealand | And 2 more authors.
Ophthalmology | Year: 2010

Purpose: To determine the independent, relative, and combined impact of reduced distance and near vision on the vision-specific quality of life (VS QOL) of adults in Timor-Leste. Design: A population-based cross-sectional eye health survey was conducted in urban and rural areas in Timor-Leste. Participants: Participants were 40 years or older. Those with better eye presenting distance vision worse than 6/18, and every third participant with 6/18 or better vision, completed the VS QOL questionnaire: in total 704 of the 1414 participants. Methods: Distance and near visual acuities were measured and eye health was assessed. The VS QOL questionnaire administered by interview was analyzed using Rasch analysis, univariate analysis, and linear regression to determine associations between VS QOL, demographic factors, and levels of visual impairment. Main Outcome Measures: The Timor-Leste VS QOL questionnaire results. Results: Rasch analysis confirmed that for participants both with and without visual impairment, the Timor-Leste VS QOL questionnaire provided a valid and reliable measure, was unidimensional, and had appropriate response categories. There was a consistent pattern of deterioration in VS QOL as vision worsened: for each category of distance- and near-vision impairment, there was an independent and significant change in Timor-Leste VS QOL scores between no visual impairment and either mild, moderate, or severe impairment (P<0.05). Combined distance- and near-vision impairment was associated with a greater impact on VS QOL than categories separately, the impact of severe distance- and near-vision impairment being the greatest and clinically significant: -3.05 (95% confidence interval [CI], -3.60 to -2.49; P<0.05; and 95% CI, <-1.0). Distance vision (37.2%) contributed relatively more than near vision (4.7%) to the total variance in VS QOL (41.9%). Older people, those not married, not literate, and rural dwellers had significantly worse Timor-Leste VS QOL scores (P<0.05). Conclusions: This study provides evidence of independent dose-response relationships between distance- and near-vision impairment and poorer VS QOL. Distance-vision impairment had a relatively larger impact on VS QOL than near-vision impairment. Combined distance- and near-vision impairment was associated with a greater impact on VS QOL compared with the independent impact of distance- or near-vision impairment at similar levels. Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article. © 2010 American Academy of Ophthalmology.

Steel D.H.W.,University of Sunderland | Sandhu S.S.,University of Sunderland | Sandhu S.S.,Center for Eye Research Australia
British Journal of Ophthalmology | Year: 2011

The exact incidence of submacular haemorrhage (SMH) in patients with neovascular age-related macular degeneration (nAMD) is unknown, and risk factors for its occurrence ill defined. It is known, however, to be a relatively common problem and important because the visual prognosis of these patients is poor. Unfortunately, patients with significant SMH were excluded from all the recent major randomised control trials for nAMD with antivascular endothelial growth factor (VEGF) agents and photodynamic therapy, and as such, the optimum management of patients is uncertain. SMH can present initially or during treatment of nAMD. The location, size, thickness and duration of SMH have an important bearing on treatment and outcomes. Thin or extrafoveal SMH are probably best treated with anti-VEGF agents alone. It has been proposed that patients with moderate-sized SMH, particularly thick haemorrhages, have an improved prognosis with surgical SMH displacement combined with treatment of CNVM if present. SMH drainage, macular translocation and RPE patch grafting are reserved for more severe extensive cases of SMH. Using these techniques, outcomes better than the natural history have been achieved. This review aims to summarise what is known about SMH in nAMD and will discuss a variety of therapeutic interventions.

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