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Ophthalmologic involvement in mitochondrial disorders

We read with interest the article by Zhu and colleagues about a retrospective study of 74 pediatric patients with a primary mitochondrial disorder (MID) and their ophthalmologic abnormalities, found in one third of this cohort. The most frequent abnormalities were pigmentary retinopathy (16%), optic atrophy (10%), progressive external ophthalmoplegia (8%), macular atrophy (3%), macular dystrophy (1%), and visual field defects (1%). We have the following comments and concerns. Not only tissues with high energy demand but generally all tissues of the eye can be affected in MIDs. The onset of clinical manifestations in a given tissue depends on the energy demand, the disease duration, and on the heteroplasmy rate in case of a mtDNA mutation. Drugs, toxins, concomitant disease, and environmental factors may further influence the progression of the disease. It is interesting to see that not a single patient with Leber’s hereditary optic neuropathy (LHON) was included. What is the reason for the absence of LHON patients in this cohort? Is it the age distribution of the cohort, were the included patients too young to develop LHON, or were LHON patients generally excluded for some reason? The authors say they have included 74 genetically confirmed MID patients. However, Table 1 lists only 71 patients. What about the three remaining patients? Which syndromic or nonsyndromic MID was diagnosed in these three patients? Which mutation did they carry? According to Table 1, 10 patients had non-syndromic MID. The authors should provide more information about the genotype and phenotype particularly of these 10 patients. Non-syndromic MIDs are of particular interest since they are more difficult to diagnose than syndromic MIDs and often overlap with more than a single syndromic MID. The authors mention that patients with Leigh syndrome were not diagnosed by genetic investigations. What were the criteria for diagnosing Leigh syndrome? MIDs are usually multiorgan disorders, variably affecting all body tissues also known as mitochondrial multiorgan disorder syndrome (MIMODS). Which other tissues or organs were affected by the genetic defect in the included patients? The presented figures about the ophthalmologic abnormalities in MID patients are uncertain due to several limitations of the study. First, the design was a retrospective one, Secondly, not all patients underwent the same battery of ophthalmologic investigations. Third, no follow-up investigation was carried out. Fourth, a number of ophthalmologic abnormalities previously reported in MID patients, such as ptosis, cataract, nystagmus, abnormalities of the cornea, ciliary body, the intraocular pressure, the choroidea, and the brain secondarily affecting the eyes, were not considered. MID patients frequently receive cocktails of vitamins, antioxidants, or cofactors, containing thiamin, riboflavin, vitamin C, coenzyme Q, idebenone, L-carnitine, or L-arginine. Did any of the 74 patients take such a cocktail and did these patients profit from the administration of these compounds? Overall, this interesting study could be further improved by a more comprehensive ophthalmologic investigation of the patients, by providing follow-up data, and by confirming the diagnosis of Leigh syndrome by genetic investigations. In patients carrying an mtDNA mutation it would be helpful to be informed about the heteroplasmy rate in various tissues.