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Review
. 2016 Jan:50:25-33.
doi: 10.1016/j.preteyeres.2015.11.001. Epub 2015 Dec 1.

Molecular diagnosis: Implications for ophthalmology

James T Rosenbaum  1 , Cailin H Sibley  2 , Dongseok Choi  3 , Christina A Harrington  4 , Stephen R Planck  5
Affiliations
Review

Molecular diagnosis: Implications for ophthalmology

James T Rosenbaum et al. Prog Retin Eye Res. 2016 Jan.

Abstract

The effort to subdivide diseases and to individualize therapies based on characteristics of the patient has been labeled precision medicine. Jameson and Longo define precision medicine as "treatments targeted to the needs of individual patients on the basis of genetic, biomarker, phenotypic or psychosocial characteristics that distinguish a given patient from other patients with similar clinical presentations" (Jameson and Longo, 2015). We illustrate how molecular diagnosis can be applied to orbital inflammatory disease to achieve the goals of precision medicine.

Keywords: Granulomatosis with polyangiitis; Molecular diagnosis; Nonspecific orbital inflammatory disease; Sarcoidosis; Thyroid eye disease; Transcriptomics.

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Conflict of interest statement

Conflict of Interest: Dr. Rosenbaum has received honoraria from Genentech which manufactures rituximab. The other authors report no conflicts of interest.

Figures

Figure 1
Figure 1
Principal coordinate analysis based on the gene expression from subjects with T (thyroid eye disease), S (sarcoidosis), G (granulomatosis with polyangiitis), or C (controls). Panel A is the discovery set; Panel B is the validation set. Each diagnosis tends to cluster indicating similarity in gene expression. The subjects with thyroid eye disease closely resemble the controls who have no known orbital disease.
Figure 2
Figure 2
Principal coordinate analysis similar to Figure 1 above except that subjects with nonspecific orbital inflammatory disease (N) are also included in panel A (discovery set) or panel B (validation set). The gene expression from tissue from subjects with NSOI is heterogeneous. A subset of subjects with NSOI have a pattern of gene expression that is very similar to the gene expression from subjects with GPA.
Figure 3
Figure 3
Venn diagram comparing the gene expression from subjects with NSOI compared to those with GPA. A total of 53,798 probe sets were studied. In the discovery set 832 probe sets were differentially expressed comparing the two diagnoses. In the validation set, 45 probe sets were differentially expressed. However, none of these 45 probe sets were also detected in the discovery set as differentially expressed. Thus there were no consistent statistically significant differences between the two diagnoses.
Figure 4
Figure 4
Heat map comparing gene expression for selected immunoglobulin related genes for various orbital inflammatory diseases. Red tones indicate increased gene expression; blue tones indicate reduced gene expression. For these selected transcripts, subjects with thyroid eye disease closely resemble the healthy controls. Subjects with GPA closely resemble the subjects with sarcoidosis. Most of the NSOI subjects resemble subjects with GPA and sarcoidosis, although some subjects with NSOI have low expression of immunoglobulin related genes similar to the controls or subjects with thyroid eye disease.
See this image and copyright information in PMC

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