Quantifying biomarkers of axonal degeneration in early glaucoma to find the disc at risk.

To evaluate regional axonal-related parameters as a function of disease stage in primary open angle glaucoma (POAG) and visual field (VF) sensitivity. Spectral domain optical coherence tomography was used to acquire 20° scans of POAG (n = 117) or healthy control (n = 52) human optic nerve heads (ONHs). Region specific and mean nerve fibre layer (NFL) thicknesses, border NFL and peripapillary NFL, minimum rim width (MRW)/ area (MRA) and prelamina thickness; and volume were compared across POAG disease stages and with visual field sensitivity. Differences identified between early glaucoma (EG), preperimetric glaucoma (PG) and control (C) ONHs included thinner PG prelamina regions than in controls (p < 0.05). Mean border NFL was thinner in EG (p < 0.001) and PG (p = 0.049) compared to control eyes; and EG mean, and inferior and ST, border NFL was thinner than in PG (p < 0.01). Mean, superior and inferior PG peripapillary NFL were thinner than in controls (p < 0.05), and EG ST peripapillary NFL was thinner than in PG (p = 0.023). MRW differences included: PG SN and inferior less than in controls (p < 0.05); thinner EG mean regional, inferior, nasal, and ST MRW versus PG MRW (p < 0.05). Regional border NFL, peripapillary NFL, MRW, MRA, prelamina thickness (except centre, p = 0.127) and prelamina volume (p < 0.05) were significantly associated with VF mean deviation (MD). Novel axon-derived indices hold potential as biomarkers to detect early glaucoma and identify ONHs at risk.

The relationship between stimulus intensity and response amplitude for the photopic negative response of the flash electroretinogram.

The aim of this study was to investigate the relationship between stimulus intensity and response amplitude for the photopic negative response (PhNR) of the flash ERG. Specific aims were (i) to determine whether a generalized Naka-Rushton function provided a good fit to the intensity-response data and (ii) to determine the variability of the parameters of the best-fitting Naka-Rushton models. Electroretinograms were recorded in 18 participants, on two occasions, using both DTL fibre and skin active electrodes, in response to Ganzfeld red stimuli (Lee filter "terry red") ranging in stimulus strength from -1.30 to 0.53 log cd.s.m(-2) (0.28-2.11 log phot td.s) presented over a steady blue background (Schott glass filter BG28; 3.9 log scot td). PhNR amplitude was measured from b-wave peak and from pre-stimulus baseline. The Naka-Rushton function was fitted to all intensity-response data, and parameters, 'n', 'Vmax' and 'K' were obtained. Coefficients of variation (CoV), and inter-ocular and inter-session limits of agreement (LoA) were calculated for both Naka-Rushton parameters. A generalized Naka-Rushton function was found to provide a good fit to the intensity-response data, except at the highest stimulus intensity, where a reduction in amplitude occurred in many individuals. The 'Vmax' parameter was less variable than 'K' for all intensity-response data. Variability was lower for DTL than skin electrodes, and for peak-to-trough PhNR measurements, compared to baseline-to-trough. This study has demonstrated for the first time that the Naka-Rushton model provides a useful means of quantifying the intensity-response relationship of the PhNR.

The s-cone PHNR and pattern ERG in primary open angle glaucoma.

PURPOSE: To compare the sensitivity of the photopic negative response (PhNR) from the shortwave (S)-sensitive and the long (L)- and medium (M)-wave-sensitive cone electroretinograms (ERGs), with the pattern electroretinogram (PERG) in the early stages of primary open-angle glaucoma (POAG). METHODS: Eighteen patients under treatment for diagnosed POAG and 19 normal control subjects were investigated. S-cone ERGs were elicited using adaptation to 650-nm light to suppress L-cone activity, and substitution between 450 nm and 535 nm to silence M-cone response at luminances higher than rod saturation. PhNRs from the L&M-cone pathways were elicited by a 200-msec pulse of red light (650 nm) on a continuous blue (450 nm) background. PERGs were recorded in accordance with the International Society for Clinical Electrophysiology of Vision (ISCEV) standard. RESULTS: Each method showed a statistically significant difference in the two groups. The S-cone PhNR was the most sensitive test and provided the most statistically significant results, with the largest area enclosed by the receiver operating characteristic (ROC) curve. CONCLUSIONS: The findings indicate that all three types of ERG may be useful in glaucoma investigation. The L- and M-cone PhNRs may have a role in monitoring established glaucoma. The previously reported high sensitivity of the PERG was confirmed. Extensive diffuse damage to S-cone bipolar and bistratified ganglion cells appears to occur at a very early stage in POAG, owing to a pressure-related mechanism, and the S-cone PhNR was the most sensitive test. It may in future have an important role in diagnosis and monitoring of early glaucoma. Further investigation of this possibility is recommended.