Major ReviewThe Negative ERG: Clinical Phenotypes and Disease Mechanisms of Inner Retinal Dysfunction
Introduction
There is a wide spectrum of retinal disorders where the primary or predominant site of dysfunction is in the inner retina. These can be either inherited or acquired, and although some are associated with characteristic fundus abnormalities, the diagnosis in the majority of these disorders is dependent upon careful electrophysiological assessment of retinal function. Full-field electroretinography (ERG) will usually show a negative (electronegative) waveform to a high intensity flash under scotopic conditions such that the inner nuclear layer derived b-wave, a positive component, is selectively reduced and the waveform is dominated by the negative a-wave. Karpe originally defined an electronegative or “negative” ERG as a waveform evoked by a bright flash with a larger a-wave than b-wave resulting in a b/a ratio below 1.0.126 In a large referral center, such as that of the authors, a negative ERG has been shown to occur in approximately 3–5% of cases referred for assessment.141, 210 In recent years advances in the fields of retinal physiology and molecular genetics have revealed data that allow a greater understanding of the pathogenesis of these disorders. This review addresses the range of disorders in which there is predominantly inner retinal dysfunction, initially summarizing the techniques used clinically to explore abnormal retinal function.
Section snippets
Photoreceptors and Phototransduction
Retinal processing involves complex mechanisms of spatio-temporal and chromatic contrast coding from the rod and cone photoreceptor outer segments to the retinal ganglion cells. The rod system is involved in scotopic or dim light vision and has low temporal resolution, characteristics that may be exploited in attempts to selectively stimulate rod and cone systems (see subsequent description). Light perception in vertebrates is mediated by a group of G protein–coupled receptors called opsins,
Probing Inner Retinal Function in Humans
Inner retinal function can be assessed through different electrophysiological and psychophysical techniques. Psychophysical tests such as dark adaptometry, color vision, or contrast sensitivity may be abnormal in inner retinal function, but do not allow the localization of dysfunction and distinction between photoreceptor and post-receptoral dysfunction. Electrophysiological techniques allow the major sites of dysfunction in the retina to be identified. The main electrophysiological procedures
Clinical Conditions
The clinician may encounter many different disorders selectively or predominantly affecting inner retinal function. The following discussion is organized according to whether the disorders are inherited, stationary or progressive, or acquired.
Conclusion
Many disorders can give rise to primary or predominant dysfunction that is post-phototransduction or inner retinal. Fundus examination is often normal in inherited inner retinal dysfunction and objective data obtained from electrophysiology is of particular importance in diagnosis. Identification of the causative genetic mutations has led to new insights into the generation of the inner retinal ERG responses. In acquired disease, the objective documentation of post-receptoral function may have
Method of Literature Search
The authors performed a Medline search with Pubmed for articles published from 1966 until September 2007. The search was restricted to publication in English language and other languages when an English abstract was available. Search terms included inner retina, inner retinal dysfunction, negative ERG, and inherited retinal disorders with inner retinal dysfunction.
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The authors want to thank the Foundation Fighting Blindness for their grant support (in particular Isabelle Audo, MD, PhD, FFB carrier development award) as well as the European Commission IP EVI-GenoRet LSHG-CT-512036 and the NHS National Institute for Healthcare Research. The authors reported no proprietary or commercial interest in any product mentioned or concepet discussed in this article.