Can data in optometric practice be used to provide an evidence base for ophthalmic public health?

Purpose: The purpose of this paper is to investigate the potential of using primary care optometry data to support ophthalmic public health, research and policy making. Methods: Suppliers of optometric electronic patient record systems (EPRs) were interviewed to gather information about the data present in commercial software programmes and the feasibility of data extraction. Researchers were presented with a list of metrics that might be included in an optometric practice dataset via a survey circulated by email to 102 researchers known to have an interest in eye health. Respondents rated the importance of each metric for research. A further survey presented the list of metrics to 2000 randomly selected members of the College of Optometrists. The optometrists were asked to specify how likely they were to enter information about each metric in a routine sight test consultation. They were also asked if data were entered as free text, menus or a combination of these. Results: Current EPRs allowed the input of data relating to the metrics of interest. Most data entry was free text. There was a good match between high priority metrics for research and those commonly recorded in optometric practice. Conclusions: Although there were plenty of electronic data in optometric practice, this was highly variable and often not in an easily analysed format. To facilitate analysis of the evidence for public health purposes a UK based minimum dataset containing standardised clinical information is recommended. Further research would be required to develop suitable coding for the individual metrics included. The dataset would need to capture information from all sectors of the population to ensure effective planning of any future interventions

Comparison of OCT and HRT Findings Among Normal, Normal Tension Glaucoma, and High Tension Glaucoma

Purpose: To evaluate the relationship between optic disc and retinal nerve fiber layer (RNFL) measurements obtained with the optical coherence tomography (OCT) and the Heidelberg retina topography (HRT) in normal, normal tension glaucoma (NTG), and high tension glaucoma (HTG). Methods: Normal, NTG and HTG subjects who met inclusion and exclusion criteria were evaluated retrospectively. One hundred seventy eyes of 170 patients (30 normal, 40 NTG, and 100 HTG) were enrolled. Complete ophthalmologic examination, HRT, OCT, and automated perimetry were evaluated. Results: Disc area, cup area and cup/disc area ratio measured with HRT were significantly different between NTG and HTG (all p0.05). Mean deviation and corrected pattern standard deviation measured by automated perimetry was significantly correlated with mean and inferior RNFL thickness in both NTG and HTG (Pearson`s r, p<0.05). Mean RNFL thickness/disc area ratio was significantly larger in HTG than NTG (35.21±18.92 vs. 31.30±10.91, p=0.004). Conclusions: These findings suggest that optic disc and RNFL damage pattern in NTG may be different from those of HTGope

The optic nerve head is the site of axonal transport disruption, axonal cytoskeleton damage and putative axonal regeneration failure in a rat model of glaucoma

The neurodegenerative disease glaucoma is characterised by the progressive death of retinal ganglion cells (RGCs) and structural damage to the optic nerve (ON). New insights have been gained into the pathogenesis of glaucoma through the use of rodent models; however, a coherent picture of the early pathology remains elusive. Here, we use a validated, experimentally induced rat glaucoma model to address fundamental issues relating to the spatio-temporal pattern of RGC injury. The earliest indication of RGC damage was accumulation of proteins, transported by orthograde fast axonal transport within axons in the optic nerve head (ONH), which occurred as soon as 8 h after induction of glaucoma and was maximal by 24 h. Axonal cytoskeletal abnormalities were first observed in the ONH at 24 h. In contrast to the ONH, no axonal cytoskeletal damage was detected in the entire myelinated ON and tract until 3 days, with progressively greater damage at later time points. Likewise, down-regulation of RGC-specific mRNAs, which are sensitive indicators of RGC viability, occurred subsequent to axonal changes at the ONH and later than in retinas subjected to NMDA-induced somatic excitotoxicity. After 1 week, surviving, but injured, RGCs had initiated a regenerative-like response, as delineated by Gap43 immunolabelling, in a response similar to that seen after ON crush. The data presented here provide robust support for the hypothesis that the ONH is the pivotal site of RGC injury following moderate elevation of IOP, with the resulting anterograde degeneration of axons and retrograde injury and death of somas

Optimising the glaucoma signal/noise ratio by mapping changes in spatial summation with area-modulated perimetric stimuli

Identification of glaucomatous damage and progression by perimetry are limited by measurement and response variability. This study tested the hypothesis that the glaucoma damage signal/noise ratio is greater with stimuli varying in area, either solely, or simultaneously with contrast, than with conventional stimuli varying in contrast only (Goldmann III, GIII). Thirty glaucoma patients and 20 age-similar healthy controls were tested with the Method of Constant Stimuli (MOCS). One stimulus modulated in area (A), one modulated in contrast within Ricco's area (C R ), one modulated in both area and contrast simultaneously (AC), and the reference stimulus was a GIII, modulating in contrast. Stimuli were presented on a common platform with a common scale (energy). A three-stage protocol minimised artefactual MOCS slope bias that can occur due to differences in psychometric function sampling between conditions. Threshold difference from age-matched normal (total deviation), response variability, and signal/noise ratio were compared between stimuli. Total deviation was greater with, and response variability less dependent on defect depth with A, AC, and C R stimuli, compared with GIII. Both A and AC stimuli showed a significantly greater signal/noise ratio than the GIII, indicating that area-modulated stimuli offer benefits over the GIII for identifying early glaucoma and measuring progression

Bioinformatic and statistical analysis of the optic nerve head in a primate model of ocular hypertension

<p>Abstract</p> <p>Background</p> <p>The nonhuman primate model of glaucomatous optic neuropathy most faithfully reproduces the human disease. We used high-density oligonucleotide arrays to investigate whole genome transcriptional changes occurring at the optic nerve head during primate experimental glaucoma.</p> <p>Results</p> <p>Laser scarification of the trabecular meshwork of cynomolgus macaques produced elevated intraocular pressure that was monitored over time and led to varying degrees of damage in different samples. The macaques were examined clinically before enucleation and the myelinated optic nerves were processed post-mortem to determine the degree of neuronal loss. Global gene expression was examined in dissected optic nerve heads with Affymetrix GeneChip microarrays. We validated a subset of differentially expressed genes using qRT-PCR, immunohistochemistry, and immuno-enriched astrocytes from healthy and glaucomatous human donors. These genes have previously defined roles in axonal outgrowth, immune response, cell motility, neuroprotection, and extracellular matrix remodeling.</p> <p>Conclusion</p> <p>Our findings show that glaucoma is associated with increased expression of genes that mediate axonal outgrowth, immune response, cell motility, neuroprotection, and ECM remodeling. These studies also reveal that, as glaucoma progresses, retinal ganglion cell axons may make a regenerative attempt to restore lost nerve cell contact.</p

Attenuated Age-Related Thinning of Peripapillary Retinal Nerve Fiber Layer in Long Eyes

PURPOSE: To assess the impact of axial length on the age-related peripapillary retinal nerve fiber layer (RNFL) thinning. METHODS: This cross-sectional observational comparative case series included 172 eyes from 172 healthy Korean subjects. Peripapillary RNFL thickness was measured using an Optic Disc Cube 200 x 200 scan of spectral domain Cirrus HD OCT and the axial length was measured using IOL Master Advanced Technology. In age groups based on decade, the normal ranges of peripapillary RNFL thickness for average, quadrant, and clock-hour sectors were determined with 95% confidence intervals. After dividing the eyes into two groups according to axial length (cut-off, 24.50 mm), the degrees of age-related RNFL thinning were compared. RESULTS: Among the eyes included in the study, 53 (30.81%) were considered to be long eyes (axial length, 25.04 +/- 0.48 microm) and 119 (69.19%) were short-to-normal length eyes (axial length, 23.57 +/- 0.60 microm). The decrease in average RNFL thickness with age was less in long eyes (negative slope, -0.12 microm/yr) than in short-to-normal length eyes (negative slope, -0.32 microm/yr) (p < 0.001). CONCLUSIONS: Age-related thinning of peripapillary RNFL thickness is attenuated in long eyes compared to short-to-normal length eyes.ope

Hydrostatic pressure does not cause detectable changes to survival of human retinal ganglion

Purpose: Elevated intraocular pressure (IOP) is a major risk factor for glaucoma. One consequence of raised IOP is that ocular tissues are subjected to increased hydrostatic pressure (HP). The effect of raised HP on stress pathway signaling and retinal ganglion cell (RGC) survival in the human retina was investigated. Methods: A chamber was designed to expose cells to increased HP (constant and fluctuating). Accurate pressure control (10-100mmHg) was achieved using mass flow controllers. Human organotypic retinal cultures (HORCs) from donor eyes (<24h post mortem) were cultured in serum-free DMEM/HamF12. Increased HP was compared to simulated ischemia (oxygen glucose deprivation, OGD). Cell death and apoptosis were measured by LDH and TUNEL assays, RGC marker expression by qRT-PCR (THY-1) and RGC number by immunohistochemistry (NeuN). Activated p38 and JNK were detected by Western blot. Results: Exposure of HORCs to constant (60mmHg) or fluctuating (10-100mmHg; 1 cycle/min) pressure for 24 or 48h caused no loss of structural integrity, LDH release, decrease in RGC marker expression (THY-1) or loss of RGCs compared with controls. In addition, there was no increase in TUNEL-positive NeuN-labelled cells at either time-point indicating no increase in apoptosis of RGCs. OGD increased apoptosis, reduced RGC marker expression and RGC number and caused elevated LDH release at 24h. p38 and JNK phosphorylation remained unchanged in HORCs exposed to fluctuating pressure (10-100mmHg; 1 cycle/min) for 15, 30, 60 and 90min durations, whereas OGD (3h) increased activation of p38 and JNK, remaining elevated for 90min post-OGD. Conclusions: Directly applied HP had no detectable impact on RGC survival and stress-signalling in HORCs. Simulated ischemia, however, activated stress pathways and caused RGC death. These results show that direct HP does not cause degeneration of RGCs in the ex vivo human retina

Quantification of Retrograde Axonal Transport in the Rat Optic Nerve by Fluorogold Spectrometry

PURPOSE: Disturbed axonal transport is an important pathogenic factor in many neurodegenerative diseases, such as glaucoma, an eye disease characterised by progressive atrophy of the optic nerve. Quantification of retrograde axonal transport in the optic nerve usually requires labour intensive histochemical techniques or expensive equipment for in vivo imaging. Here, we report on a robust alternative method using Fluorogold (FG) as tracer, which is spectrometrically quantified in retinal tissue lysate. METHODS: To determine parameters reflecting the relative FG content of a sample FG was dissolved in retinal lysates at different concentrations and spectra were obtained. For validation in vivo FG was injected uni- or bilaterally into the superior colliculus (SC) of Sprague Dawley rats. The retinal lysate was analysed after 3, 5 and 7 days to determine the time course of FG accumulation in the retina (n = 15). In subsequent experiments axona transport was impaired by optic nerve crush (n = 3), laser-induced ocular hypertension (n = 5) or colchicine treatment to the SC (n = 10). RESULTS: Spectrometry at 370 nm excitation revealed two emission peaks at 430 and 610 nm. We devised a formula to calculate the relative FG content (c(FG)), from the emission spectrum. c(FG) is proportional to the real FG concentration as it corrects for variations of retinal protein concentration in the lysate. After SC injection, c(FG) monotonously increases with time (p = 0.002). Optic nerve axonal damage caused a significant decrease of c(FG) (crush p = 0.029; hypertension p = 0.025; colchicine p = 0.006). Lysates are amenable to subsequent protein analysis. CONCLUSIONS: Spectrometrical FG detection in retinal lysates allows for quantitative assessment of retrograde axonal transport using standard laboratory equipment. It is faster than histochemical techniques and may also complement morphological in vivo analyses