Etiological distribution of isolated oculomotor nerve palsy: analysis of 633 patients and literature review.

BACKGROUND AND PURPOSE: The etiological distribution of oculomotor nerve palsy has varied amongst the studies. This study aimed to define the clinical features and underlying etiologies of isolated oculomotor nerve palsy by recruiting patients from all departments in a referral-based university hospital. METHODS: The medical records of 672 patients who had a confirmed diagnosis of isolated oculomotor nerve palsy at all departments of Seoul National University Bundang Hospital, Seongnam, South Korea, from 2003 to 2020 were reviewed. A proportion of the etiology of isolated oculomotor nerve palsy was also compared with that of patients pooled from the previous studies that were searched on PubMed in May 2022. RESULTS: The most common etiology was microvascular (n = 168, 26.5%), followed by vascular anomalies (n = 110, 17.4%), neoplastic (n = 86, 13.6%), inflammatory (n = 79, 12.5%), idiopathic (n = 60, 9.5%) and traumatic (n = 53, 8.4%). Neurologists were mainly involved in the management of microvascular and inflammatory oculomotor nerve palsies whilst ophthalmologists mainly participated in the care of idiopathic, neoplastic and traumatic palsies. Neurosurgeons mostly took care of oculomotor nerve palsy due to vascular anomalies. CONCLUSIONS: The proportion of etiologies of isolated oculomotor nerve palsy may differ according to the specialties involved in the management. The results of previous studies on the etiological distribution of isolated oculomotor nerve palsy should be interpreted with this consideration.

Mitochondrial DNA mutations in Korean patients with Leber's hereditary optic neuropathy.

In order to explore the spectrum of mitochondrial DNA (mtDNA) mutations in Korean patients with Leber's hereditary optic neuropathy (LHON), we investigated the spectrum of mtDNA mutations in 145 Korean probands confirmed with the diagnosis of LHON. Total genomic DNA was isolated from the peripheral blood leukocytes of the patients with suspected LHON, and mtDNA mutations were identified by direct sequencing. Analysis of mtDNA mutations revealed seven primary LHON mutations including the nucleotide positions (nps) 11778A (101 probands, 69.2%), 14484C (31 probands, 21.2%), 3460A (5 probands, 3.4%), and G3635A, G3733A, C4171A, and G13051A mutations in one proband each. In addition, two provisional mtDNA mutations at nps T3472C, and G13259A were each found in one proband, respectively. Another provisional mtDNA mutation at np T3394C was found in two probands. In conclusion, the spectrum of mtDNA mutations in Korean patients with LHON may differ from other ethnicities, which is characterized by high prevalence of 11778A and 14484C mutations, and a low prevalence of the 3460A mutation.

Poor visual prognosis of Asian patients with 3460 mitochondrial DNA mutation in Leber's hereditary optic neuropathy.

BACKGROUND: Among the 3 primary mutations of Leber's hereditary optic neuropathy (LHON), the incidence of LHON with a mutation at nucleotide position 3460 is the lowest in Asians. Therefore, information about the clinical manifestations of LHON mutations in Asians with the 3460 mutation is limited. OBJECTIVE: To determine the clinical manifestations including visual prognosis of Asians with the LHON 3460 mutation. METHODS: We performed a retrospective study of 5 Korean LHON patients with the 3460 mutation. RESULTS: All patients were male, and the age of onset for visual impairment varied from 17 to 35 years, with an average of 25.4 ± 7.16 years. Among the 10 affected eyes, only 1 eye of 1 patient showed visual improvement to 20/50 at 2 years after onset. The remaining patients had a visual acuity of worse than 20/200. CONCLUSION: The visual prognosis of Korean patients with the LHON 3460 mutation was generally poor. Further studies regarding Asian patients with the LHON 3460 mutation are necessary.

Efficacy of 3D-printed eye model to enhance retinoscopy skills.

We conducted a prospective study to evaluate the efficacy of simulation-based education using a three-dimensional (3D)-printed schematic eye model in improving the retinoscopy refraction skills of medical students. A schematic eye model was printed using a fused deposition modeling-based 3D printer. Twenty medical students randomized into 3D (n = 10) and control (n = 10) groups received a 1-h lecture on the principles and methods of manifest refraction and were shown how to use the retinoscope and sciascope bars. The 3D group additionally attended a tutorial on the schematic eye. Both groups performed refractive examinations on four eyes of volunteer patients, and the results were recorded as a baseline. Instructor feedback and refraction practice was provided with the 3D group or with control group. To account for subject fatigue, patients spent no more than 8 min on the examination. After a 1-h break to allow for fatigue and familiarity, refraction tests were repeated on four randomly selected eyes of patients. Students' refraction readings were compared with the autorefractor values using a spherical equivalent value and blur strength. All participants measured the time required to complete the refraction test and reported their subjective confidence in the results of each refraction test. Refractive errors before and after training did not differ between the control and 3D groups, with a significant improvement in errors observed in both groups (p = 0.005 and 0.008, respectively). The time to complete refraction before and after training did not differ between the two groups, both of which showed a significant reduction in time (p = 0.005 and 0.028, respectively). Pre- and post-training confidence scores for the accuracy of each refraction on a 10-point Likert scale were not significantly different. However, when comparing score changes between pre- and post-training, only the control group showed a significant increase in confidence (p = 0.005). Tests for the non-inferiority of refractive errors after training indicated that the 3D group was non-inferior to the control group. In conclusion, training in retinoscopy refraction skills using a 3D-printed eye model resulted in significant improvement in accuracy and speed compared to practice with real patients. Except for better confidence in the control group, schematic eye model training was not inferior to practice with real patients.

Self-Reported Findings of the Korean Intermittent Exotropia Multicenter Study Questionnaire.

PURPOSE: To determine subjective symptoms and medical history of patients with intermittent exotropia in a large study population. METHODS: The Korean Intermittent Exotropia Multicenter Study (KIEMS) is a nationwide, observational, cross-sectional, multicenter study conducted by the Korean Association for Pediatric Ophthalmology and Strabismus including 5,385 patients with intermittent exotropia. Subjective symptoms and medical history of patients with intermittent exotropia were extracted by a comprehensive survey based on a self-administered questionnaire according to the study protocol of the KIEMS. RESULTS: The mean age of symptom onset was 5.5 years. The most common symptom reported in patients with intermittent exotropia was photophobia (52.1%), followed by diplopia at near fixation (7.3%) and distance fixation (6.2%). Preterm birth was found in 8.8%, and 4.1% had perinatal complications. A family history of strabismus was present in 14.9%, and 5.5% of patients had a family member who underwent strabismus surgery. CONCLUSIONS: The KIEMS is one of the largest clinical studies on intermittent exotropia. Intermittent exotropia frequently caused photophobia and diplopia, and patients with a family history was not uncommon.

Novel Variant of FDXR as a Molecular Etiology of Postlingual Post-Synaptic Auditory Neuropathy Spectrum Disorder via Mitochondrial Dysfunction: Reiteration of the Correlation between Genotype and Cochlear Implantation Outcomes.

Objectives: FDXR encodes the mitochondrial ferredoxin reductase, which is associated with auditory neuropathy spectrum disorder (ANSD) and optic atrophy. Only two studies have described FDXRrelated hearing loss. The auditory rehabilitation outcomes of this disease entity have not been investigated, and the pathophysiologic mechanism is not well elucidated. Here we report a hearingimpaired subject with co-segregation of the FDXR variant and post-synaptic type ANSD, who underwent cochlear implantation (CI) with favorable outcomes. We suggest a possible pathophysiologic mechanism of adult-onset ANSD via mitochondrial dysfunction. Methods: A 35-year-old woman was ascertained to have ANSD. Exome sequencing identified the genetic cause of hearing loss, and functional study measuring mitochondrial activity was performed to provide molecular evidence of pathophysiology. Expression of FDXR in the mouse cochlea was evaluated by immunohistochemistry. Intraoperatively, electrically-evoked compound action potential (ECAP) responses were measured, and mapping parameters were adjusted accordingly. Audiological outcomes were monitored for over 1 year. Results: In lymphoblastoid cell lines (LCLs) carrying a novel FDXR variant, decreased ATP and MtMP levels and increased ROS levels were observed compared to control LCLs. These dysfunctions were restored by administering mitochondria isolated from umbilical cord mesenchymal stem cells, confirming the pathogenic potential of this variant via mitochondrial dysfunction. Partial ECAP responses during CI and FDXR expression in the mouse cochlea indicate that FDXR-related ANSD is postsynaptic. By increasing the pulse width during mapping, the patient's CI outcomes showed significant improvement over 1-year post-CI. Conclusion: Post-synaptic ANSD due to a novel FDXR variant linked to mitochondrial dysfunction was identified first in a Korean, and 1-year post CI outcomes were reported for the first time in the literature. Excellent audiologic results were obtained, and our results reiterate the correlation between genotype and CI outcomes in ANSD.