A new era of uveitis: impact of polymerase chain reaction in intraocular inflammatory diseases

Abstract

Uveitis is a sight-threatening intraocular inflammatory disorder which may occur from both infectious and non-infectious or autoimmune causes. The frequency of infectious uveitis and autoimmune uveitis varies depending on countries and regions. According to a nationwide survey conducted by the Japanese Ocular Inflammation Society, infectious and non-infectious uveitis accounted for 16.4 and 50.1% of new patients, respectively while the remaining 33.5% of new uveitis cases were not classified or were idiopathic uveitis. Infectious uveitis is particularly important because it causes tissue damage to the eye and may result in blindness unless treated. However, it can be treated if the pathogenic microorganisms are identified promptly and accurately. Remarkable advancements in molecular and immunological technologies have been made in the last decade, and the diagnosis of infectious uveitis has been greatly improved by the application of molecular and immunological investigations, particularly polymerase chain reaction (PCR). PCR performed on a small amount of ocular samples provides a prompt, sensitive, and specific molecular diagnosis of pathogenic microorganisms in the eye. This technology has opened a new era in the diagnosis and treatment of uveitis, enabling physicians to establish new clinical entities of uveitis caused by infectious microorganisms, identify pathogens in the eyes of many patients with uveitis, and determine prompt diagnosis and appropriate therapy. Here we review the PCR process, new PCR tests specialized for ocular diseases, microorganisms detected by the PCR tests, diseases in the eye caused by these microorganisms, and the clinical characteristics, diagnosis, and therapy of uveitis.

Evaluation of a Multiplex Strip PCR Test for Infectious Uveitis: A Prospective Multicenter Study

“…Its use has been validated for ocular samples. 4,6,7,10,11,15 In addition, it is difficult to test for viruses using other traditional methods, such as culturebased and microscopy-based tests, and antibody-based tests require large amounts of sample. After performing the Shapiro-Wilk test for normality and the Levene test for distribution and variance of samples in each population, the Pearson correlation coefficient was calculated for the copy numbers (copies/mL) obtained by qPCR and the Cq values (cycles) obtained by Strip PCR.…”

“…It covers 9 of the main pathogens responsible for infectious uveitis, excluding other pathogens and unknown pathogens. In addition, Strip PCR includes pathogens like EBV 5,11 for which the mechanism of infectious uveitis is not yet established. Strip PCR and conventional qPCR were unable to detect pathogens with late Cq values in 3 samples, because of their detection limits ( Supplemental Table S9; Supplemental Material available at AJO.com), which need to be addressed by repeating the test multiple times.…”

“…O CULAR INFECTIOUS DISEASES ARE OFTEN DIFFIcult to diagnose because they are caused by a wide variety of pathogens. 1,2 Although quantitative polymerase chain reaction (qPCR) is the standard method for the etiologic examination, [3][4][5][6][7][8][9][10][11] its complexity and lack of a standardized protocol, including different primers, prevent its widespread use. Our aim was to develop a standardized convenient real-time PCR test, which would be equivalent to qPCR in targeting the main pathogens of ocular infectious diseases, with a kit that will yield consistent results in different laboratories with different users, while permitting use with relative ease.…”

HTLV-1 in Ophthalmology

“…Infiltration of ATL cells into the eye provides a specific sign, which we have termed the "knob-like ATL cell multiple ocular infiltration" (KAMOI) sign. At the ocular surface, this KAMOI sign can be seen most prominently at the bulbar conjunctiva around the corneal limbus and at the palpebral conjunctiva around each lacrimal punctum Mochizuki et al, 2017; Figure 4A). KAMOI sign can also be detected in the retina (Kamoi and Ohno-Matsui, 2020; Figure 4B).…”

Autoimmunity, Autoinflammation, and Infection in Uveitis

“…3 Infections are proven causes of some cases of uveitis. [4][5][6][7] In others, activation of innate immune processes in response to infection may cause tissue damage through a mechanism of autoinflammation.…”