Issues Affecting The Eyes / Vision
Vision is a very energy-dependent biologic function. The retina and optic nerve are particularly dependent on mitochondrial oxidative phosphorylation (Carelli, 2006). Defects in oxidative phosphorylation with disruption of ATP production can lead to retinal degeneration (Cooper, 2003) and abnormalities on electroretinography (Isashiki, 1998). The extraocular muscles also have a high content of mitochondria and a high metabolic rate (Carelli, 2006).
The hallmark clinical findings are ophthalmoplegia, ptosis, optic neuropathy with atrophy, pigmentary retinopathy, and cortical visual field defects with scotomata (Johns, 1995). Nystagmus is a less common finding in mitochondrial disease, usually indicating cerebellar atrophy or brainstem involvement (Finsterer, 2006). Leber hereditary optic neuropathy may be the most common form of mitochondrial disease (Chinnery, 2000).
Symptomatically, patients may complain of night blindness, an early sign of retinitis pigmentosa leading to degeneration of the photoreceptor cells in the retina. With progression, peripheral vision is more affected (Listernick, 2007). Central blindness is often a late finding (Listernick, 2007). Blurring may be caused by retinopathy and diplopia occurs in patients with ophthalmoplegia (Richardson, 2005). However, much more common is transient blurring and double-vision that can occur in association with generalized muscle fatigue and which improves with rest and amelioration of the fatigue.
Alacrima or dry eyes can occur in mitochondrial disease, not unlike Sjogren syndrome (Axelrod, 2006), and may be related to autonomic dysfunction or autoimmune disease.
Finally, patients with migraine or seizures can develop unilateral or bilateral vision impairment that resolves as the seizure ends or headaches dissipates. Vision or visual field defects that occur during a stroke-like episode may not show complete resolution.
Mitochondrial Differential Diagnosis
1. Mitochondrial eye disease -
a. Permanent disease due to the underlying mitochondrial disease
b. Temporary symptoms associated with significant fatigue, migraine, seizures, or stroke-like episodes
2. Muscle -
a. Permanent weakness
b. Temporary weakness associated with significant fatigue, migraine or seizures
1. Determine what symptoms are associated with the visual problems and whether or not there are any trigger factors (such as fatigue).
2. Are the effects temporary or permanent/progressive?
1. An ophthalmologist is an important specialist to monitor a patient with mitochondrial disease. A formal examination includes evaluation of acuity, dark adaptation, visual fields, and visual function.
2. When changes in function or visual ability occur, consultation with a neuro-ophthalmologist and electroretinography may provide extra information.
3. If patients are experiencing transient visual loss, a referral to a neurologist should be considered for evaluation of migraine, seizures, or stroke-like episodes.
4. Where acuity is moderate-severely compromised, a referral should be made to a program that provides services to the visually-challenged population.
Axelrod F, Chelimsky GG, Weese-Mayer DE. Pediatric autonomic disorders. Pediatrics 2006;118;309-21.
Carelli V, Barboni P, Sadun AA. Mitochondrial ophthalmology. In Mitochondrial Medicine. DiMauro S, Hirano M, Schon EA, eds. Informa Healthcare, Abingdon UK, 2006, 105-42.
Chinnery PF, Johnson MA, Wardell TM, et al. The epidemiology of pathogenic mitochondrial DNA mutations. Ann Neurol 2000;48(2);188-93.
Cooper LL, Hansen RM, Darras BT, Korson M, et al. Rod photoreceptor function in children with mitochondrial disorders. Arch Ophthalmol 2002;120(8):1055-62.
Finsterer J. The central nervous system manifestations of mitochondrial disorders. Acta Neurol Scand 2006;114(4):217-38.
Isashiki Y, Nakagawa M, Ohba N, et al. Retinal manifestations in mitochondrial diseases associated with mitochondrial DNA mutations. Acta Ophthalmol Scand 1998;76(1);6-13.
Johns DR. Mitochondrial DNA and disease. N Engl J Med 1995;333(10);638-44.
Listernick R. A 9-year old boy with labored breathing. Pediatr Ann 2007;36(5):254-7.
Richardson C, Smith T, Schaefer A, et al. Ocular motility findings in chronic progressive external ophthalmoplegia. Eye 2005;19(3):258-63.