Molecular diagnosis: Implications for ophthalmology

Abstract

The effort to subdivide diseases and to individualize therapies based on characteristics of the patient has been labelled 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.

Gene Expression Profiling and Heterogeneity of Nonspecific Orbital Inflammation Affecting the Lacrimal Gland

“…All tissues had been reviewed by an ophthalmic pathologist from the contributing center and then further reviewed by two additional pathologists (DJW and HEG) who collaborated in the preparation of this report. These centers and the pathologists have previously used a similar method of tissue collection to analyze gene expression from a variety of orbital diseases including TED 13 , GPA 12 , sarcoidosis 16 , and nonspecific orbital inflammation 14 . Control tissue from healthy individuals was obtained at the time of cosmetic surgery or blepharoplasty.…”

“…These centers and the ocular pathologists have previously used a similar method of tissue collection to analyze gene expression from a variety of orbital diseases, including TED, 13 GPA, 12 sarcoidosis, 16 and NSOI. 14 Control tissue from healthy individuals was obtained at the time of cosmetic surgery or blepharoplasty. In some instances, surgeons removed portions of normal lacrimal gland if the gland prolapsed during the course of orbital surgery.…”

“…For example, gene expression profiling can distinguish different causes of synovitis, esophagitis, or myocarditis . Our group previously used gene expression profiling to characterize different causes of uveitis and orbital adipose tissue inflammation . In another study, our group analyzed gene expression in blood, lacrimal gland, and orbital adipose tissue from individuals affected by sarcoidosis.…”

“…9 Our group previously used gene expression profiling to characterize different causes of uveitis 10,11 and orbital adipose tissue inflammation. [12][13][14][15] In another study, 16 our group analyzed gene expression in blood, lacrimal gland, and orbital adipose tissue from individuals affected by sarcoidosis. In that study, a set of 40 messenger RNA transcripts was selected that were differentially expressed in all 3 diseased tissue samples of patients compared with the same tissue samples from healthy controls.…”

Ocular sarcoidosis

“…[40 ▪ ] Furthermore, mRNA transcripts which are either up or down regulated in lacrimal gland or orbital adipose tissue are often similarly altered in whole blood. [41] This suggests the possibility that the measurement of gene expression in peripheral blood could ultimately become an accurate diagnostic modality for sarcoidosis or for identifying the cause of orbital inflammatory disease. Pathway analsysis suggests that transcripts which are upregulated in blood, orbital fat and lacrimal gland from patients with sarcoidosis are frequently regulated by the transcription factors, interferon response factors 1 and 2 and nuclear factor kappa B [42 ▪ ].…”