Negative electroretinograms: genetic and acquired causes, diagnostic approaches and physiological insights

The dark-adapted human electroretinogram (ERG) response to a standard bright flash includes a negative-going a-wave followed by a positive-going b-wave that crosses the baseline. An electronegative waveform (or negative ERG) results when the b-wave is selectively reduced such that the ERG fails to cross the baseline following the a-wave. In the context of a normally sized a-wave, it indicates a site of retinal dysfunction occurring after phototransduction (commonly at the photoreceptor to bipolar cell synapse). This is an important finding. In genetic disease, the pattern of ERG abnormality can point to variants in a small group of genes (frequently those associated with congenital stationary night blindness and X-linked retinoschisis, but negative ERGs can also be seen in other conditions including syndromic disease). In acquired disease, there are numerous causes, but specific features may point to melanoma-associated retinopathy (MAR). In some cases, the visual symptoms precede the diagnosis of the melanoma and so the ERG findings can initiate investigations facilitating early detection and treatment. Negative ERGs can occur in other paraneoplastic conditions, and in a range of other diseases. This review will outline the physiological basis for the negative ERG, report prevalences in the literature from different cohorts, discuss the range of causes, displaying examples of a number of ERG phenotypes, highlight features of a clinical approach to patients, and briefly discuss further insights relating to current flows shaping the a-wave trough and from single-cell transcriptome analysis.

Diagnostic Value of ERG in Prostate Needle Biopsies Containing Minute Cancer Foci

Background: Prostate carcinoma (PC) is the second most diagnosed cancer in men population worldwide. The small amount of the tissue in prostate needle biopsy is often sufficient for the correct interpretation. Novel antibodies, as ERG, could add to the diagnostic value of IHC study in analysing difficult core biopsies. Aim: The aim of the present study was to establish a diagnostic use of ERG in a work-up of prostate needle biopsies containing minute PC, individually and in combination with AMACR/34βE12. Materials and methods: From total number of 1710 consecutive prostate needle biopsies based on HE stain 114 biopsies containing minute PC. Selected biopsies were incubated with anti-ERG, AMACR and 34βE12 antibodies using immunohistochemical technique. Results: Among 98 selected biopsies, 57 showed positive and 41 negative ERG staining. AMACR staining was positively expressed in 86 of the cases and completely absent in remaining 12. In 9 of the AMACR-negative cases the final diagnosis was establish by manifestation of ERG expression in the tumour foci. 95 of the biopsies demonstrated lack of 34βE12 expression and only 3 cases showed weak patchy staining. Among these cases 2 were ERG-positive. Conclusion: ERG antibody could be especially helpful in the cases with controversial expression of AMACR and 34βE12.