Mitochondrial retinopathy
Kearns and Sayre described patients with “pigmentary degeneration” on funduscopy, night vision abnormalities, and some histologic similarities, but also clinical differences, to retinitis pigmentosa Subsequently, the retinal phenotype of KSS was described as retinitis pigmentosa, atypical retinitis pigmentosa, tapetoretinal degeneration, salt-and-pepper retinopathy, and pigmentary retinopathy. As the clinical characterization, however, was not always comprehensive the term "mitochondrial retinopathy" appears most accurate and the diagnosis of RP may have been imprecise. Patients with KSS show widespread granular pigmented alterations in the posterior fundus which correspond to granular patterns on fundus autofluorescence imaging. Associated changes on optical coherence tomography (OCT) include reflectivity changes predominantly at the level of the ellipsoid and interdigitation zone and an increased distance between the ellipsoid band and the retinal pigment epithelium. Night blindness may be seen in patients with KSS. Visual acuity loss is usually mild and only occurs in 40–50% of patients. Cardiac conduction abnormalities
These most often occur years after the development of ptosis and ophthalmoplegia. Atrioventricular (abbreviated "AV") block is the most common cardiac conduction deficit. This often progresses to a Third-degree atrioventricular block, which is a complete blockage of the electrical conduction from the atrium to the ventricle. Symptoms of heart block include syncope, exercise intolerance, and bradycardia. Cerebral folate deficiency
Kearns-Sayre patients are consistently found to have cerebral folate deficiency, a syndrome in which 5-MTHF levels are decreased in the cerebrospinal fluid despite being normal in serum.
One of the patients had characteristic KSS, while the other patient had a very different disease known as Pearson marrow pancreas syndrome. Complicating the matter, in some cases Pearsons syndrome has been shown to progress into KSS later in life.More recent studies have concluded that mtDNA duplications may also play a significant role in determining what phenotype is present. Duplications of mtDNA seem to be characteristic of all cases of KSS and Pearsons syndrome, while they are absent in CPEO.Deletions of mtDNA in KSS vary in size (1.3–8kb), as well as position in the mitochondrial genome. The most common deletion is 4.9kb and spans from position 8469 to position 13147 on the genome. This deletion is present in approximately ⅓ of people with KSS

Diagnosis
A neuro-ophthalmologist is usually involved in the diagnosis and management of KSS. An individual should be suspected of having KSS based upon clinical exam findings. Suspicion for myopathies should be increased in patients whose ophthalmoplegia does not match a particular set of cranial nerve palsies (oculomotor nerve palsy, fourth nerve palsy, sixth nerve palsy). Initially, imaging studies are often performed to rule out more common pathologies. Diagnosis may be confirmed with muscle biopsy, and may be supplemented with PCR determination of mtDNA mutations. Biopsy findings
It is not necessary to biopsy an ocular muscle to demonstrate histopathologic abnormalities. Cross-section of muscle fibers stained with Gömöri trichrome stain is viewed using light microscopy. In muscle fibers containing high ratios of the mutated mitochondria, there is a higher concentration of mitochondria.