In this issue, of JNO, Drs. Deborah I. Friedman and Mark L. Moster discuss the following 4 journal articles: Jonzzon S, Price A, Troung N, Naftel RP, Phillips PH, Wellons JC, Isaacs AM. Neuro-ophthalmological findings in...In this issue, of JNO, Drs. Deborah I. Friedman and Mark L. Moster discuss the following 4 journal articles: Jonzzon S, Price A, Troung N, Naftel RP, Phillips PH, Wellons JC, Isaacs AM. Neuro-ophthalmological findings in pediatric ventricular shunt failure: a systematic review. J Neurosurg Pediatr. 2025;36:29-35. doi: 10.3171/2024.12.PEDS24397.Barton JJS, Özturan G. The varieties of junctional scotoma: 17 cases, a review, and a taxonomy. Eye (Lond). 2025;39:1673-1687. doi: 10.1038/s41433-025-03789-z.Shah SK, Indurkar A, Patel BK. Surgical management and visual outcomes of optic-pathway cavernous malformations: A comprehensive literature review of 80 reported cases (1979-2025). Clin Neurol Neurosurg. 2025;256:108988. doi: 10.1016/j.clineuro.2025.108988.Ko J, Lee MJ, Khwarg SI, Yoon JS, Yang SW, Son J, Kim N, Lew H; Multicenter Study Committee of the Korean Society of Ophthalmic Plastic and Reconstructive Surgery. Immunoglobulin G4-related ophthalmic disease: A Nationwide Multicenter Study in Korea. Ophthalmology. 2025;132:995-1004. doi: 10.1016/j.ophtha.2025.04.031.
BACKGROUND: CN III is a pure motor cranial nerve that innervates the majority of the extraocular muscles. CN III palsy is the most common cranial nerve palsy with an incidence of 3-4 cases per 100,000. EVIDENCE ACQUISITI...BACKGROUND: CN III is a pure motor cranial nerve that innervates the majority of the extraocular muscles. CN III palsy is the most common cranial nerve palsy with an incidence of 3-4 cases per 100,000. EVIDENCE ACQUISITION: High-resolution, 3-dimensional, skull base MRI allows for high spatial resolution and high signal-to-noise ratio allowing for optimal evaluation of CN III pathology by segment. RESULTS: A systemic approach is used to describe the segmental anatomy of CN III, its vascular supply, clinical pathologic manifestations, and imaging correlate. CONCLUSIONS: We present a segmental approach to high-resolution 3-dimensional MRI of the oculomotor nerve from nuclear to extraforaminal segments.
BACKGROUND: The aim of this study was to evaluate the retinal safety profile of flow-diverting stents in the treatment of carotid-ophthalmic aneurysms with ophthalmic artery coverage. METHODS: In this cohort study, patie...BACKGROUND: The aim of this study was to evaluate the retinal safety profile of flow-diverting stents in the treatment of carotid-ophthalmic aneurysms with ophthalmic artery coverage. METHODS: In this cohort study, patients treated with a flow-diverting stent for carotid-ophthalmic aneurysm were prospectively included from January 2021 to January 2023. A systematic ophthalmological examination was performed before and at 15 days and at 6 months after the procedure. We compared the retinal thickness and the vascular density of the retinal capillary plexuses using optical coherence tomography (OCT). RESULTS: Twenty-five patients were included (median age: 52.3 years, range: 36.6 to 76.4; women: 92.4%). Postoperative retinal events were reported in 24% patients (cotton wool spots in 6 patients [24%], retinal hemorrhages in 3 patients [12.5%]), with no functional repercussions detected on examination. The macular vascular framework assessed by OCT-angiography remained unchanged postoperatively. We observed immediate postoperative foveal thinning and temporal papillary optic fiber thickening which was not clinically significant. After 6 months, all clinical events had resolved, and both macular and peripapillary OCT had returned to normal. CONCLUSIONS: This study provides evidence for retinal safety when using flow-diverting stents covering the ophthalmic artery. Fundus changes may occur in the postoperative course, but without impact on visual function.
BACKGROUND: To report the association of downbeat nystagmus and chin-down head posture with cerebellar dysfunction and the results of treatment with bilateral superior rectus recession and bilateral inferior oblique ante...BACKGROUND: To report the association of downbeat nystagmus and chin-down head posture with cerebellar dysfunction and the results of treatment with bilateral superior rectus recession and bilateral inferior oblique anteriorization. METHODS: This is a retrospective series of patients with cerebellar ataxia treated for downbeat nystagmus, oscillopsia, and abnormal head posture with bilateral superior rectus recession and bilateral inferior oblique anteriorization between 2000 and 2022. RESULTS: Four patients underwent the procedure. All 4 patients had systemic signs and symptoms of cerebellar ataxia, confirmed by a neurologist as well as MRI findings involving the cerebellum. All patients had oscillopsia, downbeat nystagmus with damping in up gaze, and chin-down head posture. All patients underwent bilateral superior rectus recession and bilateral inferior oblique anteriorization. Median follow-up period was 3 years. Oscillopsia in primary position and abnormal head posture resolved in all patients. CONCLUSIONS: Downbeat nystagmus with oscillopsia associated with cerebellar disorders respond well to surgical treatment with bilateral superior rectus recession and bilateral inferior oblique anteriorization.
The 2025 Jacobson Lecture revealed a scientific journey that began with the Cuban epidemic of blindness to recent studies of the quantum mechanical underpinnings of Leber's Hereditary Optic Neuropathy (LHON). A sudden ou...The 2025 Jacobson Lecture revealed a scientific journey that began with the Cuban epidemic of blindness to recent studies of the quantum mechanical underpinnings of Leber's Hereditary Optic Neuropathy (LHON). A sudden outbreak of bilaterally symmetrical optic neuropathy and peripheral neuropathy in more than 50,000 Cubans in 1993 had been blamed on a viral infection. Further investigations by our team revealed synergistic toxicity of folic acid deficiency and the consumption of homemade rum containing small amounts of methanol. This research led to subsequent findings relevant to LHON, a maternally inherited mitochondrial disease involving Complex I, resulting in retinal ganglion cell death. Later studies show that this was not due to the depletion of adenosine triphosphate but through the accumulation of reactive oxygen species (ROS). The quantum mechanical model, which identifies alterations of quantum electron tunneling as the origin of spilled ROS, changes our understanding of mitochondrial optic neuropathies and redefines LHON as a disease of oxidative stress rather than energy deficit.
BACKGROUND: Retrograde trans-synaptic retinal degeneration (RTSD) occurs after injury to the postgeniculate visual pathways, and the distribution of retinal thinning mirrors the pattern of visual field defects (VFDs), wh...BACKGROUND: Retrograde trans-synaptic retinal degeneration (RTSD) occurs after injury to the postgeniculate visual pathways, and the distribution of retinal thinning mirrors the pattern of visual field defects (VFDs), which reflects the topographical organization of the visual pathway. We aimed to quantitatively assess how RTSD evolves over time in a topographically specific manner based on lesion location and to identify factors associated with its progression. METHODS: This longitudinal cohort study included patients with RTSD caused by structural lesions in the visual pathway, including 29 patients who have had a stroke and 22 with tumors. Optical coherence tomography was used to measure the thickness of the peripapillary retinal nerve fiber layer (pRNFL) and the macular ganglion cell-inner plexiform layer (mGCIPL) in RTSD and non-RTSD areas, defined by the side and VFD patterns. A mixed-effects model was applied to evaluate the longitudinal changes in pRNFL and mGCIPL thickness over the follow-up period and to identify associated factors. RESULTS: In the RTSD area, the estimated rate of pRNFL thinning was 6.44 µm/log year (95% confidence interval [CI], 4.85-8.02 µm/log year), whereas the estimated rate of mGCIPL thinning was 5.44 µm/log year (95% CI, 4.66-6.21 µm/log year). Thinning was most pronounced during the first 4 years, after which the rate of thinning slowed and stabilized at 0.33 µm/year (95% CI, -0.30 to 0.97 µm/year) for pRNFL and 0.31 µm/year (95% CI, 0.06-0.56 µm/year) for mGCIPL. The thinning rates in the RTSD area were significantly faster than those in the non-RTSD area (pRNFL: 3.50 µm/log year [95% CI, 2.30-4.70 µm/log year], P = 0.005; mGCIPL: 0.29 µm/log year [95% CI, -0.14 to 0.72 µm/log year], P < 0.001). Older age, male sex, and more severe VFD were associated with faster RTSD progression. Regarding the causes, RTSD progression did not differ significantly between stroke and tumor, but hemorrhagic stroke and malignant tumors (glioblastoma, metastatic) showed faster thinning than ischemic stroke and meningioma, respectively. CONCLUSIONS: RTSD progression was pronounced in both the pRNFL and mGCIPL during the first 4 years, with greater severity observed in areas topographically linked to the brain lesion. Although RTSD developed regardless of lesion etiology, older age, male gender, severe VFD, intracerebral hemorrhage, and malignant tumors were associated with significantly faster progression.
BACKGROUND: C12orf65 (chromosome 12 open reading frame 65) gene encodes a mitochondrial matrix protein essential for the release of newly synthesized proteins from mitochondrial ribosomes. Biallelic pathogenic variants r...BACKGROUND: C12orf65 (chromosome 12 open reading frame 65) gene encodes a mitochondrial matrix protein essential for the release of newly synthesized proteins from mitochondrial ribosomes. Biallelic pathogenic variants result in loss of function in the protein complex necessary for oxidative phosphorylation. Pathogenic C12orf65 variants have been associated with various inherited neurological diseases, including Behr syndrome, Leigh syndrome, combined oxidative phosphorylation deficiency 7, and hereditary spastic paraplegia. METHODS: This was a retrospective case series of 4 children with C12orf65 mutation from 3 unrelated pedigrees of Chinese descent. Clinical and diagnostic data were collected via retrospective medical record review. The phenotypic manifestations were systematically documented, and the genotypic data were analyzed in conjunction with previous reports. RESULTS: Four subjects exhibited optic nerve atrophy, strabismus, progressive lower limb dystonia, and abnormal gait. Whole exome sequencing revealed the c.394C>T variant in C12orf65 in all 4 patients. Three of the patients had coexisting novel MT-ND4 (m.11696 G>A) and OPA1 (c.1817G>A) variants. CONCLUSIONS: We analyzed the gene-phenotypic associations of 4 patients in conjunction with previous reports which added to the current understanding of C12orf65 -related neurodegenerative disorders. The superimposed mutations in 2 of these patients suggest that the heterogeneity of optic neuropathy and the systemic features associated with C12orf65 pathogenic variants may be altered by the genetic background of mitochondrial or nuclear genes that influence mitochondrial function. We recommend genetic evaluation of C12ORF65-related diseases, including other genes responsible for optic neuropathy, and not just limited to Sanger sequencing.