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Alex J. Shortt, Hannah J. Levis, Peter Blows, Stephen J. Tuft, Julie T. Daniels; Standardized Outcome Measures For Limbal Stem Cell Transplantation. Invest. Ophthalmol. Vis. Sci. 2012;53(14):1715.
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To design, validate and test the reliability of a system for quantifying treatment outcomes in corneal limbal stem cell deficiency (LSCD)
A range of clinical, biological and functional outcomes were investigated. To quantify the clinical signs of LSCD, standardized grading plates of increasingly severe LSCD were designed so that corneal haze, neovascularization, irregularity and epithelial integrity could be independently graded from corneal photographs. Grading was performed masked and independently by a grading technician and a clinician. Validity and reliability were tested using photographs from 26 patients with varying degrees of LSCD. Inter and intra-observer variability were calculated. Confocal microscopy (CM) and impression cytology were investigated as potential tools for quantifying cell morphology. Both were performed on 10 patients prior to and following limbal stem cell (LSC) transplantation. Visual acuity (VA) data from 14 patients treated with LSC transplantation were used to investigate the optimal means of handling and presenting this data a meaningful functional outcome.
Validity of the photograph grading system was confirmed by the fact that objective scores reflected the subjective appearance of corneas and the spread of scores reflected the varying levels of LSCD severity. The system had a score range of 0 to 12. The mean difference (SD) in score between observers was 0.39(0.8) and the 95% levels of agreement were +1.96 & -1.19. The repeatability for observer 1 was 1.567 and observer 2 was 2.478 (i.e. 95% of the time, the observer would assign scores within this difference or less). A treatment success was arbitrarily defined as reduction of score by four points or more. This allowed survival curves to be plotted. It was not possible to design a reliable method of quantifying CM changes but CM was useful in determining whether the cornea was covered by a monolayer or multilayered epithelium and whether normal cell boundaries were forming indicating healthy cells and normal differentiation. Impression cytology and cytokeratin profiling of limited additional value. The most effective way of reporting visual acuity, based on range of data available were using pre- versus post-op plots and also bar charts demonstrating the number of lines lost or gained
Using the described combination of objectively graded clinical features, imaging of cellular morphology and standardized representation of visual results it was possible to analyze the outcomes of LSC transplantation in a cohort of 14 patients to level of detail that far exceeds any measures currently in use. As these are standardized and validated they will enable comparison of outcomes between different studies and techniques
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