Re-epithelialization is a complex process that involves migration and proliferation of keratinocytes, in addition to the production of cytokines and growth factors that affect other cells. The induction of transcription factors during these processes is crucial for successful wound healing. The transcription factor forkhead boxO-1 (FOXO1) has recently been found to be an important regulator of wound healing. In particular, FOXO1 has significant effects through regulation of transforming growth factor-beta (TGF-β) expression and protecting keratinocytes from oxidative stress. In the absence of FOXO1, there is increased oxidative damage, reduced TGF-β1 expression, reduced migration and proliferation of keratinocytes and increased keratinocytes apoptosis leading to impaired re-epithelialization of wounds.
Statistically significant visual improvement was observed in association with anti-vascular endothelial growth factor therapy in patients with severe neovascular age-related macular degeneration, even in patients whose initial VA was worse than that studied in large anti-vascular endothelial growth factor clinical trials. Numerous clinically discernable or potentially modifiable factors may influence outcome in such patients.
Purpose
To evaluate sensitivity, specificity, and reproducibility of color difference plot analysis (CDPA) of 103-Hexagon multifocal electroretinogram (mfERG) in detecting established hydroxychloroquine (HCQ) retinal toxicity.
Methods
23 patients taking HCQ were divided into those with and without retinal toxicity, and were compared with a control group without retinal disease and not taking HCQ. CDPA with two masked examiners was performed using age-corrected mfERG responses in the central ring (Rc; 0 to 5.5 degrees from fixation) and paracentral ring (Rp; 5.5 to 11 degrees from fixation). An abnormal ring was defined as containing any hexagons with a difference of 2 or more standard deviations from normal (color blue or black).
Results
Categorical analysis (ring involvement or not) showed Rc had 83% sensitivity and 93% specificity. Rp had 89% sensitivity and 82% specificity. Requiring abnormal hexagons in both Rc and Rp yielded sensitivity and specificity of 83% and 95% respectively. If required in only one ring, they were 89% and 80%, respectively. In this population, there was complete agreement in identifying toxicity when comparing CDPA using Rp with ring ratio analysis using R5/R4 P1 ring responses (89% sensitivity, 95% specificity). Continuous analysis of CDPA with receiver operating characteristic analysis showed optimized detection (83% sensitivity, 96% specificity) when ≥4 abnormal hexagons were present anywhere within the Rp ring outline. Intergrader agreement and reproducibility were good.
Conclusions
CDPA had sensitivity and specificity that approached that of ring ratio analysis of R5/R4 P1 responses. Ease of implementation and reproducibility are notable advantages of CDPA.
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