The ability of electrophysiological testing to provide objective evidence of function at different levels of the visual system enables accurate localization of dysfunction in the vast majority of patients. This chapter provides an overview of lesion localization in clinical practice; it does not set out to address specific diseases in detail; those are covered elsewhere in this volume. The patients and disorders chosen to illustrate diagnostic points have been selected merely to be representative for the nature of the associated electrophysiological findings. Referencing has also been restricted, and the reader is referred to the relevant chapters of this volume or to another standard text (e.g., Fishman et al.⁴) for more information, particularly clinical details, on specific diseases.

Conventional clinical diagnosis relates the symptoms, history, and family history reported by the patient to the signs found on examination. The difficulties in accurate lesion localization based purely on this approach are clearly manifest in the visual system. For example, night blindness can arise from disorders of the photoreceptors, such as retinitis pigmentosa (RP) or enhanced S-cone syndrome, or may arise post-phototransduction, as in X-linked congenital stationary night blindness or melanoma-associated retinopathy. Fundus examination might not be helpful; a retina may look grossly normal on ophthalmoscopic examination but not function normally, as in Leber congenital amaurosis or vitamin A deficiency. Also, the degree of intraretinal pigment deposition in a patient with RP may be a poor indicator of the extent of retinal degeneration; there may be only mild pigmentary changes but profound loss of function. Equally, an abnormal retinal appearance may be associated with normal function, such as in a choroideremia carrier. Further, blurring of vision, central field loss, color vision disturbance, and a relative afferent pupillary defect can occur in macular dysfunction but are more commonly associated with optic nerve disease. Many diagnostic dilemmas can be resolved by appropriate electrophysiological testing.

The approach adopted relates to the nature of the electrophysiological findings. In summary, the electro-oculogram (EOG) will give information regarding the function of the retinal pigment epithelium (RPE) and its interaction with the photoreceptors. Electroretinography (ERG) assesses the photoreceptor and inner nuclear layers of the retina, with additional diagnostic dissection enabled in the cone system by the use of short-wavelength stimulation to assess the function of the S-cone pathway and long-duration stimulation to separate the function of the ON (depolarizing) and OFF (hyperpolarizing) pathways associated with L- and M-cones. If disease is confined to the macula, the full-field ERG will be unaffected, and pattern electroretinography (PERG) or multifocal electroretinography (mfERG) is needed. The reader is reminded that these tests of central retinal function are technically demanding; both are small signals, and the latter is particularly dependent on the ability of the patient to maintain accurate fixation. The PERG consists of two main components: P50 and N95. Although much of P50 arises in relation to spiking cell function, it is driven by the macular photoreceptors, and P50 component amplitude may be used to assess macular function quantitatively. The function of the retinal ganglion cells, which do not significantly contribute to the routine clinical full-field ERG, is objectively measured using the PERG N95 component. The cortical visual evoked potential (VEP) enables conclusions to be drawn regarding the intracranial visual pathways, including the optic nerves, the optic chiasm, and the visual cortex. However, it should always be borne in mind that the VEP is a “downstream” response that arises largely in the visual cortex and, as such, can be affected by disease anywhere “upstream” in the visual system, exemplified by the delayed pattern VEP common in macular disease. Thus, a combined approach, incorporating and integrating information from different tests, might be needed for accurate disease characterization and lesion localization.⁷