Also known as dominant optic atrophy, Kjer's optic neuropathy is an autosomally inherited disease that affects the optic nerves, causing reduced visual acuity and blindness beginning in childhood. Dominant optic atrophy is due to mitochondrial dysfunction mediating the death of optic nerve fibers. It was first described clinically by Batten in 1896 and named Kjer’s optic neuropathy in 1959 after Danish ophthalmologist Poul Kjer, who studied 19 families with the disease. Although Kjer's optic neuropathy is the most common autosomally inherited optic neuropathy (disease of the optic nerves), it is often misdiagnosed.
Kjer's optic neuropathy usually affects both eyes roughly symmetrically in a slowly progressive pattern of vision loss beginning in childhood. Vision testing will reveal areas of impaired visual acuity (scotomas) in the central visual fields with peripheral vision sparing and impaired color vision (color blindness). Visual acuity loss varies from mild to severe, typically ranging from 6/6 (in meters, equivalent to 20/20, ft) to 6/60 (20/200, ft) with a median value of 6/36 (roughly equivalent to 20/125 ft), corrected vision. In rare cases, vision loss is more severe. Characteristic changes of the fundus evident on examination is temporal pallor (indicating atrophy) of the optic disc and in its end stage, excavation of the optic disc, as is also seen in Leber hereditary optic neuropathy and normal tension glaucoma.
Since the onset of Kjer's optic neuropathy is insidious, symptoms are often not noticed by the patients in its early stages and are picked up by chance in routine school eye screenings. First signs of Kjer's typically present between 4–6 years of age, though presentation at as early as 1 year of age has been reported. In some cases, Dominant optic atrophy may remain subclinical until early adulthood. Progression of dominant optic atrophy varies even within the same family.
Kjer's Optic Neuropathy Pathophisiology
Vision loss in Dominant optic atrophy is due to optic nerve fiber loss from mitochondria dysfunction. Dominant optic atrophy is associated with mutation of the OPA1 gene found on chromosome 3, region q28-qter. Also, 5 other chromosomal genes are described causing optic atropy: OPA2 (x-linked), OPA3 (dominant), OPA4 (dominant), OPA5 (dominant) and OPA6 (recessive) (see OMIM 165500).
The OPA1 gene codes for a dynamin-related GTPase protein targeted to the mitochondrial inner membrane. Although the mechanism of action of the OPA1 gene product is unknown, it is likely involved in stabilization of mitochondrial membrane complexes. OPA1 has been implicated in the fusion of mitochondrial inner membranes during mitochondrial fusion events, indicating that a mitochondrial fusion dysfunction may be important in the development of OPA1 related optic atrophy. Mitochondria are subcellular structures that generate and transform energy from metabolism into discrete usable units (ATP) for the cell’s functions.