Inherited Retinal Diseases (IRD)

The ISCEV Guide to Electrodiagnostic Procedures advises using electrophysiology (ERG, mfERG, PERG, PhNR, EOG) responses are objective measures of retinal function and assist in accurately differentiating between IRDs as well as judging the severity of the specific IRD. The information from these tests can also assist with counseling and developing life management skills. In addition, ERG and the psychophysical tests (DA and FST) assist with gene therapy trials that may improve outcomes for people born with an IRD. 

Visual electrophysiology for IRDs

Bestrophinopathies 

Bestrophinopathies are a recognizable phenotype of degenerative eye diseases caused by inherited mutations in the BEST1 gene. BEST1 mutations may also play a role in other ophthalmic diseases like rod-cone dystrophy and early-onset cataracts. Bestrophinopathies are characterized by abnormal ocular development, which leads to impaired function in the retinal pigment epithelium (RPE) layer resulting in yellowish sub-retinal lesions. 

All bestrophinopathies are characterized by a decreased electrooculogram (EOG) Arden ratio (light peak/dark trough). Both full-field ERG (ffERG) and multifocal ERG (mfERG) can assist in differentiating within the phenotype as well as tracking the progression of the condition. 

Congenital Achromatopsia 

Congenital Achromatopsia is a hereditary vision disorder characterized by lack of cone vision due to malfunction of the retinal phototransduction pathway. The cone photoreceptors are unable to properly respond to a light stimulus. People with achromatopsia are partially or totally color blind. They also have poor visual acuity, photophobia, and pendular nystagmus. Currently, there are four known gene mutations that cause this disorder. There are two subtypes in this condition and both types have abnormal ERG recordings with preservation of the rod-mediated ERG. Patients with the more severe subtype show nondetectable cone function in an ERG test while patients with the less severe subtype show some residual cone function. Gene therapy studies of animal models of human achromatopsia have had some success in recovering cone function. 

Congenital Stationary Night Blindness 

Congenital Stationary Night Blindness (CSNB) is a clinically and genetically heterogeneous group of hereditary retinal disorders primarily affecting the photoreceptors, although the retinal pigment epithelium and the bipolar cells may also be affected. Types within this group differ in electrophysiological characteristics as well as fundus appearance and mode of inheritance. The full-field ERG can assist in diagnosing different forms of CSNB. 

Leber Congenital Amaurosis 

Leber Congenital Amaurosis (LCA) is a group of hereditary retinal diseases causing the most severe form of IRD in which both rods and cones are either nonfunctional at birth or are lost within the first years of life. It is also the most common cause of inherited blindness in children. 

LCA is characterized by a severely reduced or non-detectable scotopic and photopic ERG response. DiagnosysFST® was used in the first-ever successful gene therapy drug trial for (LUXTURNA™) by Spark Therapeutics. DiagnosysFST® is now used clinically for the assessment of vision pre and post LUXTURNA™ treatment.

Leber’s Hereditary Optic Neuropathy 

Leber Hereditary Optic Neuropathy (LHON) is a common inherited mitochondrial disorder and typically affects young males more than females. The disorder leads to degeneration of the retinal ganglion cells with painless sub-acute central vision loss in one or both eyes during the young adult years. 

Studies show that the PhNR amplitude is significantly decreased in people with LHON and can distinguish carriers from controls. Treatment options are limited but include the use of antioxidant supplements. Gene therapy trials are currently underway. 

Retinitis Pigmentosa 

Retinitis Pigmentosa (RP), also known as rod-cone degeneration, is the most common form of IRD. RP is a group of eye disorders that causes progressive vision loss as the rod photoreceptors degenerate in the early stages of the disease, followed by cone cell death. 

Full-field electroretinograms (ERGs) are valuable in diagnosing early-stage retinitis pigmentosa (RP), often detecting the condition before any fundus abnormalities become visible through ophthalmoscopy. Dark adaptation is typically prolonged; therefore, dark adaptometry (DA) can also be helpful in identifying early cases of the disease. 

Stargardt Disease 

Stargardt Disease is a common form of inherited macular degeneration. Electroretinograms (ERGs) provide useful information to assist in counseling and life management skills. Research is ongoing to help minimize vision loss due to this condition. ERGs and psychophysical tests are also being used in clinical trials for this condition. 

Usher Syndrome 

Usher Syndrome causes combined progressive hearing and vision loss. Newborns often have moderate to severe hearing impairment while symptoms of retinitis pigementosa (RP) start shortly after adolescence.  

Full-field electroretinograms (ERGs) aid in the early diagnosis of retinitis pigmentosa (RP), often identifying the condition before any visible fundus abnormalities can be detected with an ophthalmoscope. Dark adaptometry (DA) can also be valuable in early detection, as RP typically causes prolonged dark adaptation. 

X-linked Retinoschisis 

X-linked Retinoschisis (XLRS) is an inherited disease caused by mutations in the Retinoschisin 1 gene that causes loss of central and peripheral vision characterized by abnormal splitting within the inner retinal layers. 

The full-field ERG is useful in diagnosing X-linked retinoschisis (XLRS), as patients often show a reduced b-wave with a preserved a-wave under dark-adapted conditions, called an electronegative response. Meanwhile, full-field stimulus threshold (FST) testing is typically normal or near normal in XLRS. These functional tests offer valuable insights into XLRS abnormalities and may aid in future clinical trials.