Juvenile open-angle Glaucoma associated with Leber's hereditary optic neuropathy: a case report and literature review

Abstract

Background: Leber's hereditary optic neuropathy (LHON) is a maternally inherited recessive disease rarely complicated with glaucoma. We conducted a clinical and genetic retrospective case series to describe three cases of juvenile open-angle glaucoma (JOAG) and an ND4 m11778G > A mitochondrial DNA (mtDNA) mutation, which is pathognomonic for LHON.

Case presentation: Patient 1 was a 16-year-old boy diagnosed with bilateral JOAG and high myopia. His intraocular pressure (IOP) was poorly controlled with the use of full topical anti-glaucoma medications. His best-corrected visual acuity (BCVA) decreased gradually over 5 years. Fundoscopic examination revealed bilateral enlarged disc cupping of the optic nerves with sectorial excavation and reduction of the neural rim in the left eye. His visual field (VF) was characterized by bilateral progressive central scotoma. Pattern visual evoked potentials (VEPs) and pattern electroretinograms (ERGs) showed extinguished responses in both eyes. Because of the non-specific visual field findings and the optic neuropathy disclosed by the pattern VEPs and pattern ERGs, we arranged a genetic test for the patient, which revealed an m11778G > A mtDNA mutation. Patient 2, the younger brother of Patient 1, was a 15-year-old boy who had been diagnosed with bilateral JOAG in 2010. The BCVA of both eyes remained at 1.0 during the follow-up period. Fundoscopic examination revealed bilateral mildly paled optic disc with enlarged cupping and reduction of the neural rim. The pattern ERG revealed a decreased N95 amplitude bilaterally. The genetic test revealed an m11778G > A mtDNA mutation. Patient 3 was a 35-year-old man with bilateral JOAG. His BCVA decreased gradually over 10 years. Fundoscopic examination revealed paled optic disc with enlarged disc cupping and reduction of the neural rim in both eyes. The pattern ERG revealed a decreased N95 amplitude bilaterally. The genetic test revealed an m11778G > A mtDNA mutation.

Conclusions: This case series describes three patients with concomitant occurrence of JOAG and LHON. These two diseases may have a cumulative effect on oxidative stress and retinal ganglion cell death with the rapid deterioration of vision, which may occur during adolescence.

Keywords: Juvenile open-angle glaucoma; Leber’s hereditary optic neuropathy; Mitochondria.

Fig. 1

Fundoscopic photographs of the right eye (a) and left eye (b) of Patient 1. The fundoscopic photographs of Patient 1 revealed bilateral enlarged disc cupping of the optic nerves with sectorial excavation and reduction of the neural rim in the left eye

Fig. 2

Optical coherence tomography angiography and vessel density results of the right eye (upper) and left eye (lower) of Patient 1. The optical coherence tomography angiography of Patient 1 revealed retinal nerve fiber layer thinning over the upper and lower temporal quadrants and upper nasal quadrant of the right eye and retinal nerve fiber layer thinning at the temporal quadrant and upper nasal quadrant of the left eye. The peripapillary vascularity of the capillary was 43.6% for the right eye and 49.15% for the left eye. Both eyes revealed a decrease in the sectoral division of the temporal regions

Fig. 3

The visual fields of the right eye (a) and left eye (b) of Patient 1 in 2013 and the visual fields of the right eye (c) and left eye (d) of Patient 1 in 2016 The visual field (30–2 SITA standard) was characterized by bilateral progressive central scotoma in the eyes from 2013 to 2016. *SITA: Swedish interactive thresholding algorithm.

Fig. 4

The electroretinogram (ERG), pattern visual evoked potential (VEP) and pattern ERG results of Patient 1. The full-field ERG was subnormal for both eyes, and there were more decreased amplitudes in the right eye than there were in the left eye, but there was no obvious implicit time delay noted. The pattern VEP and pattern ERG results showed bilateral extinguished responses in the eyes. *ERG: electroretinogram; VEP: visual evoked potential

Fig. 5

The family pedigrees of Patient 1 and Patient 2. Patient 1 and Patient 2 were both diagnosed with JOAG and an mtDNA m11778 G > A mutation. The genetic tests revealed an mtDNA ND4 m11778G > A mutation in the younger brother, younger sister, and mother. *mtDNA: mitochondrial DNA; y/o: year-old

Fig. 6

Fundoscopic photographs of the right eye (a) and left eye (b) of Patient 2. Fundoscopic photographs of Patient 2 revealed bilateral mildly paled optic disc with enlarged cupping and bilateral reduction of the neural rim in the eyes

Fig. 7

Optical coherence tomography angiography and vessel density results of the right eye (upper) and left eye (lower) of Patient 2. Optical coherence tomography angiography of Patient 2 revealed retinal nerve fiber layer thinning at the upper nasal quadrant of the left eye

Fig. 8

The electroretinogram (ERG), pattern visual evoked potential (VEP) and pattern ERG results of Patient 2. The pattern VEP showed no delay, and the pattern ERG revealed decreased amplitudes for N95 in both eyes. *ERG: electroretinogram; VEP: visual evoked potential

Fig. 9

Fundoscopic photographs of the right eye (a) and left eye (b) of Patient 3. Fundoscopic photographs of Patient 3 revealed paled optic disc with enlarged disc cupping of the optic nerves and sectorial excavation and reduction of the neural rim in both eyes

Fig. 10

Optical coherence tomography angiography and vessel density results of the right eye (upper) and left eye (lower) of Patient 3. Optical coherence tomography angiography of Patient 3 disclosed diffuse RNFL thinning and a bilateral decrease in the peripapillary vascularity in the eyes

Fig. 11

The electroretinogram (ERG), pattern visual evoked potential (VEP) and pattern ERG results of Patient 3. The ERG result was subnormal in both eyes, and the pattern ERG revealed decreased amplitudes for N95 in both eyes. *ERG: electroretinogram; VEP: visual evoked potential