Oxidative Stress in Antibiotic Toxic Optic Neuropathy Mimicking Acute LHON in a Patient with Exacerbation of Cystic Fibrosis

Abstract

The striking similarity of disc edema without leakage on fluorescein angiography, which is pathognomonic of Leber hereditary optic neuropathy (LHON), was present in a patient with cystic fibrosis with antibiotic toxic optic neuropathy. This similarity suggested the common effect of oxidative stress on retinal ganglion cells in inherited mitochondrial and antibiotic optic neuropathies. We present the case of a patient with advanced cystic fibrosis on chronic antibiotic treatment who experienced a rapid painless bilateral visual decline over a course of a few weeks. At examination, his corrected visual acuity was reduced to 0.3 in both eyes, with dyschromatopsia and central scotoma. The appearance of the fundus resembled the typical clinical features of acute LHON with hyperemic optic discs and tortuous vessels with no dye leakage from the optic discs on fluorescein angiography. Ganglion cell layer loss was seen on optic coherence tomography, with all findings pointing to LHON. Genetic testing did not reveal any LHON-specific mutations. After extended genetic testing, a heterozygous variant c.209C>T in the OPA3 gene on chromosome 19, g.46032648G>A, classified as a variant of unknown significance, was also found. After discontinuing antibiotics and general improvements in his health, surprisingly, his visual function completely improved. Later, he also received a bilateral lung transplant that further improved his general condition, and his vision remained normal. Excluding LHON, the transient optic neuropathy in our patient could be mainly due to antibiotic toxicity of linezolid and ciprofloxacin, which have been linked to mitochondrial dysfunction and advanced cystic fibrosis with hypoxic status. We suggest the possibility that patients with cystic fibrosis may be more prone to developing mitochondrial optic neuropathy, especially with additional risk factors such as chronic antibiotic therapy, which affect mitochondrial function, and can perhaps serve as a model for LHON.

Oxidative Stress: A Suitable Therapeutic Target for Optic Nerve Diseases?

“…Nutritional deficits, such as in case of vitamin B12 (cyanocobalamin), B1 (thiamine), or B9 (folic acid) deficiency, as well as intoxications, caused, for example, by ethambutol, amiodarone, or antibiotics, such as chloramphenicol [556][557][558], may cause optic nerve disorders. The prevalence of these pathologies is variable and typically depends on social, economic, geographical, and historical factors [31,32].…”

“…Both intoxications or vitamin deficiencies usually manifest with optic disc pallor and anomalies in the papillomacular nerve fiber bundle and symptomatically through reduced color perception and detectable visual field defects, corresponding to the central or cecocentral scotomas, as observed in cases of LHON [556,562]. For example, toxic optic neuropathies caused by a chronic intake of chloramphenicol can mimic an acute stage of LHON [558]. Chloramphenicol can suppress mitochondrial protein synthesis, inducing an alteration in the mitochondrial structure and subsequently, dysfunction, with decreasing ATP and increasing ROS, which collectively reflect in LHON-like symptoms [563].…”

Oxidative Stress: A Suitable Therapeutic Target for Optic Nerve Diseases?

“…Nutritional deficits, such as in case of vitamin B12 (cyanocobalamin), B1 (thiamine) or B9 (folic acid) deficiency, as well as intoxications, caused for example by ethambutol, amiodarone, or also antibiotics such as chloramphenicol [553][554][555], may cause optic nerve disorders. Prevalence of these pathologies is variable and typically depends on social, economic, geographical and historical factors [31,32].…”

“…Both intoxications or vitamin deficiencies usually manifest with optic disc pallor and anomalies in the papillomacular nerve fiber bundle, and symptomatically through reduced color perception and detectable visual field defects, corresponding to central or cecocentral scotomas, as observed in cases of LHON [559,560]. For example, toxic optic neuropathies caused by a chronic intake of chloramphenicol, can mimic an acute stage of LHON [555]. Chloramphenicol can suppress a mitochondrial protein synthesis, inducing alteration in the mitochondrial structure and subsequently dysfunction, with decreasing ATP and increasing ROS, which collectively reflect in a LHON-like symptomatic [561].…”