Analysis of the initial orbital MRI in aquaporin-4 antibody-positive optic neuritis (AQP4-ON): lesion location and lesion length can be predictive of visual prognosis.

PURPOSE: Despite mounting evidence indicating that aquaporin-4 antibody-positive optic neuritis (AQP4-ON) presents a less favorable prognosis than other types of optic neuritis, there exists substantial heterogeneity in the prognostic outcomes within the AQP4-ON cohort. Considering the persistent debate over the role of MRI in assessing the prognosis of optic neuritis, we aim to investigate the correlation between the MRI appearance and long-term visual prognosis in AQP4-ON patients. METHODS: We retrospectively reviewed the ophthalmological and imaging data of AQP4-ON patients admitted to our Neuro-ophthalmology Department from January 2015 to March 2018, with consecutive follow-up visits for a minimum of 3 years. RESULTS: A total of 51 AQP4-ON patients (59 eyes) meeting the criteria were enrolled in this research. After assessing the initial orbital MR images of each patient at the first onset, we observed the involvement of the canalicular segment (p < 0.001), intracranial segment (p = 0.004), optic chiasm (p = 0.009), and the presence of LEON (p = 0.002) were significantly different between recovery group and impairment group. For quantitative measurement, the length of the lesions is significantly higher in the impairment group (20.1 ± 9.3 mm) than in the recovery group (12.5 ± 5.3 mm) (p = 0.001). CONCLUSION: AQP4-ON patients with involvement of canalicular, intracranial segment and optic chiasm of the optic nerve, and the longer range of lesions threaten worse vision prognoses. Timely MR examination during the initial acute phase can not only exclude the intracranial or orbital mass lesions but also indicate visual prognosis in the long term.

Adult-onset neuronal intranuclear inclusion disease related retinal degeneration: a Chinese case series.

Purpose: To evaluate adult-onset neuronal intranuclear inclusion disease (NIID)-related retinopathy with guanine-guanine-cytosine repeat expansions in NOTCH2NLC. Materials and methods: Neuro-ophthalmic evaluations, including best-corrected visual acuity, slit-lamp biomicroscopy, intraocular pressure (IOP), ultrasound biomicroscopy, pupillometry, fundus photography, fundus autofluorescence (FAF), optical coherence tomography (OCT), Humphrey visual field, full-field electroretinography (ERG), and multifocal ERG (mf-ERG) were performed in patients with gene-proven NIID. Results: Nine patients (18 eyes) were evaluated, with a median age of 62 years (55-68) and only one man was included in our study. Six patients presented with decreased visual acuity or night blindness, whereas the other three were asymptomatic. The visual acuity was measured from 20/200 to 20/20. Miosis was present in eight patients, four of whom had ciliary process hypertrophy and pronation, and three of whom had shallow anterior chambers. Fundus photography, FAF, and OCT showed consistent structural abnormalities mainly started from peripapillary areas and localized in the outer layer of photoreceptors and inner ganglion cell layer. ERG and mf-ERG also revealed retinal dysfunction in the corresponding regions. Conclusion: Patients with NIID showed both structural and functional retinopathies which were unique and different from common cone-rod dystrophy or retinitis pigmentosa. Patients with miosis may have a potential risk of an angle-closure glaucoma attack. Neuro-ophthalmic evaluations is essential for evaluating patients with NIID, even without visual symptom.

Giant Cell Arteritis Presenting With Ocular Symptoms: Clinical Characteristics and Multimodal Imaging in a Chinese Case Series.

Purpose: To evaluate demographic and clinical characteristics of a Chinese population with giant cell arteritis using multimodal imaging focusing on ophthalmic examinations. Design: Retrospective observational case series. Materials and Methods: In the neuro-ophthalmology division of the Eye, Ear, Nose, and Throat Hospital, Shanghai, we evaluated the demographic and clinical characteristics of patients diagnosed with giant cell arteritis between January 2016 and June 2021. Results of routine ophthalmic examinations including fundus examination, optical coherence tomography, color duplex ultrasonography of ocular and superficial temporal arteries, orbital magnetic resonance imaging, and superficial temporal artery biopsy were evaluated. Results: A total of 15 patients (22 eyes; ten male and five female) were evaluated with a mean age of 77.0 ± 8.5 years. Among them, seven had bilateral involvement that occurred simultaneously or sequentially. Twelve patients presented with arteritic anterior ischemic optic neuropathy, two with arteritic anterior ischemic optic neuropathy combined with cilioretinal artery occlusion, and one with cotton-wool spots. In acute stages of optic neuropathy and retinopathy, optical coherence tomography revealed optic disc edema, thickening of the inner retinal nerve fiber layer and ganglion cell layer, and loss of layer structure. In late stages, optical coherence tomography revealed diffuse atrophy of the inner retina. The "halo" sign was observed in 12 patients in the superficial temporal artery ultrasound, and seven out of eight patients who underwent biopsy demonstrated classic giant cell arteritis pathological changes. Most patients having poor visual acuity but ability to perceive light; 10/22 eyes had permanent vision loss. Conclusion: Although rare in Asians, giant cell arteritis may be underdiagnosed among elderly Chinese patients presenting with anterior ischemic optic neuropathy. Non-invasive superficial temporal artery ultrasound detecting inflammatory thickening of the intima as the "halo" sign combined with routine elevated erythrocyte sedimentation rate and C-reactive protein may be helpful in diagnosing patients with a high probability of having giant cell arteritis.

Varying Clinical Phenotypes of Mitochondrial DNA T12811C Mutation: A Case Series Report.

The T12811C mitochondrial DNA (mtDNA) mutation has been reported in Leber hereditary optic neuropathy (LHON) previously, with vision loss as the main manifestation. The involvement of other organ systems, including the central and peripheral nervous system, heart, and extraocular muscles, has not been well described. This case series report investigated four patients with T12811C mtDNA mutation, verified through a next generation sequencing. Two male patients presented with bilateral subacute visual decrease combined with involvement of multiple organ systems: leukoencephalopathy, hypertrophic cardiomyopathy, neurosensory deafness, spinal cord lesion and peripheral neuropathies. Two female patients presented with progressive ptosis and ophthalmoplegia, one of whom also manifested optic atrophy. This study found out that patients harboring T12811C mtDNA mutation manifested not only as vision loss, but also as a multi-system disorder affecting the nervous system, heart, and extraocular muscles.

Cancer-associated retinopathy after anti-programmed death 1 (PD-1) antibody for treating hepatocellular carcinoma--a case report of a Chinese patient.

PURPOSE: Programmed death-1 (PD-1) receptor antibody immune therapy has been widely used for treating solid tumors, and cancer-associated retinopathy after the anti-PD1 treatment have not been reported yet. We report a Chinese patient presenting with acute constriction of visual fields after nivolumab treatment for hepatocellular carcinoma. The diagnosis of cancer-associated retinopathy was confirmed with optical coherence tomography, electroretinography, and positive results for recoverin paraneoplastic antibodies. OBSERVATIONS: A 57-year-old Chinese man complained of acute visual fields constriction in both eyes for 20 days. He was diagnosed with hepatocellular carcinoma 5 months earlier and treated with chemotherapy for 4 months. He was administered 100 mg of nivolumab as an immune checkpoint inhibitor treatment once every 2 weeks. After 2 cycles of nivolumab, he presented with acute visual problems and was referred to a neuro-ophthalmologist. Brain magnetic resonance imaging excluded optic nerve infiltration and brain metastasis. Optical coherence tomography revealed binocular diffuse loss of outer retinal structures like the circumferential fovea of the macula, and full-field electroretinography showed an almost extinguished response. A serum anti-paraneoplastic antibody panel was positive for anti-recoverin antibodies. He was diagnosed with cancer-associated retinopathy. He was treated with systemic steroids, followed by tryptophan immunoadsorption for 3 cycles. His visual field had slightly improved at a 2-year follow-up. CONCLUSIONS AND IMPORTANCE: Although paraneoplastic retinopathy could be diagnosed in tumor patients, acute-onset vision disturbance after anti-PD-1 treatment might be related to complications of the immune checkpoint inhibitor therapy. Cancer-associated retinopathy, as well as uveitis and optic neuropathy, might arise after anti-PD-1 therapy.

Clinical characteristics of optic neuritis phenotypes in a 3-year follow-up Chinese cohort.

To evaluate the clinical characteristics of optic neuritis (ON) with different phenotypes. This prospective study recruited patients with new-onset ON between January 2015 and March 2017 who were followed-up for 3 years. They were divided into the myelin oligodendrocyte glycoprotein-seropositive (MOG-ON), aquaporin-4-seropositive (AQP4-ON), and double-seronegative (seronegative-ON) groups, and their clinical characteristics and imaging findings were evaluated and compared. Two-hundred-eighty patients (405 eyes) were included (MOG-ON: n = 57, 20.4%; AQP4-ON: n = 98, 35.0%; seronegative-ON: n = 125, 44.6%). The proportion of eyes with best-corrected visual acuity > 20/25 at the 3-year follow-up was similar between the MOG-ON and seronegative-ON groups; the proportion in both groups was higher than that in the AQP4-ON group (p < 0.001). Relapse rates were higher in the MOG-ON and AQP4-ON groups than in the seronegative-ON group (p < 0.001). Average retinal nerve fiber layer (RNFL) thickness at 3 years was similar between the MOG-ON and AQP4-ON groups (63.41 ± 13.39 and 59.40 ± 11.46 µm, p = 0.476) but both were thinner than the seronegative-ON group (74.06 ± 11.14 µm, p < 0.001). Macular ganglion cell-inner plexiform layer (GCIPL) revealed the same pattern. Despite RNFL and GCIPL thinning, the MOG-ON group's outcome was as favorable as that of the seronegative-ON group, whereas the AQP4-ON group showed unsatisfactory results.

Oculomotor Nerve Palsy Due to Unusual Causes.

BACKGROUND: An isolated oculomotor nerve (CN III) palsy is a diagnostic concern because of the potential for serious morbidity or life-threatening causes. We present 5 unusual causes of oculomotor nerve palsy that escaped initial diagnosis in order to raise awareness of their associated features that will facilitate correct diagnosis. METHODS: This study consisted of a retrospective analysis of clinical features and imaging of 5 patients who were referred for neuro-ophthalmologic evaluation with presumed diagnosis of oculomotor nerve palsy of unknown reasons. RESULTS: A complete CN III palsy and an inferior division CN III palsy were diagnosed with a schwannoma in the cavernous sinus and orbital apex portion, respectively; a middle-aged woman with aberrant regeneration was found to have a small meningioma; an adult man with ptosis was diagnosed with cyclic oculomotor paresis with spasms; and a patient after radiation was diagnosed with neuromyotonia. CONCLUSIONS: Localizing the lesion of oculomotor nerve palsy and careful examination of the imaging is crucial. Aberrant regeneration, cyclic pupil changes, and past medical history of amblyopia, strabismus, or radiation are also very helpful for diagnosis.

Neurosarcoidosis presenting as CRVO combined CRAO: a biopsy-proven case report of a Chinese patient.

BACKGROUND: Neurosarcoidosis is a rare systemic disorder that can affect the eye and other organs, including the central nervous system. Neurosarcoidosis infiltrating the optic nerve presenting as central retinal vein occlusion combined with artery ischaemia has not been reported in the literature previously. We describe a Chinese patient presenting with acute monocular vision loss, in whom an optic nerve biopsy confirmed the diagnosis of neurosarcoidosis. CASE PRESENTATION: A 47-year-old woman complained of acute decreased vision in her left eye over the course of 1 month. She reported that her vision deteriorated quickly within first 3 days of consulting an ophthalmologist at a local hospital. She was diagnosed with central retinal vein occlusion after funduscopic examination and fundus fluorescein angiography, and the vision in her left eye further deteriorated to no light perception. An orbital magnetic resonance imaging showed an abnormal T1-weighted image of the optic nerve after contrast enhancement. She was referred to a neuro-ophthalmologist for further evaluation. After routine blood tests ruled out infectious and metastatic diseases, she was prescribed 500 mg/d methylprednisolone for 5 days, but her vision did not improve. As she could still not perceive light, an optic nerve biopsy was performed, and the histopathology revealed non-necrotising granuloma that was consistent with neurosarcoidosis. CONCLUSIONS: Isolated optic nerve infiltration by neurosarcoidosis without the involvement of the central nervous system or other systemic organs is challenging to diagnose. Biopsy of the optic nerve sheath is crucial for the final diagnosis of neurosarcoidosis. Therefore, a comprehensive ophthalmologic and systemic examination and work-up for inflammation of the eye, chest, and central nervous system should be conducted for atypical cases.

Pseudotumour Cerebri Syndrome in China: A Cohort Study.

Pseudotumour cerebri syndrome (PTCS) remains to be fully investigated in Chinese patients and our study reported PTCS-related clinical differences between Chinese patients and Western patients. This study enrolled 55 consecutive patients (females: 44, median age: 37 y, age range: 14-62 y) with PTCS diagnosed from October 2015 to December 2017. Nine (16.4%, females) patients had primary PTCS, and 46 (83.6%) had secondary PTCS (P = 0.001). At presentation, 81.8% of patients had grade >3 papilloedema, with 23.6% having diffusely constricted fields. Mean subarachnoid space around the optic nerve measured by retrobulbar ultrasonography during lumbar puncture was 1.12 ± 0.17 mm and decreased to 0.86 ± 0.11 mm after treatment. Optical coherence tomography (OCT) showed that 92.9% of eyes with intact macular ganglion cell-inner plexiform layer (GCIPL) at baseline had good outcomes after treatment. Patients' demographic and clinical characteristics showed that secondary PTCS was more common than primary idiopathic intracranial hypertension in Chinese patients. Polycystic ovarian syndrome was the main associated factor in females. Poor visual function was common at presentation. Noninvasive ocular ultrasonography and OCT are the prognostic indicators of PTCS treatment in intracranial pressure and visual function, respectively, after PTCS treatment.

Diagnostic Performance of MALDI-TOF MS Compared to Conventional Microbiological Cultures in Patients with Suspected Endophthalmitis.

Purpose: To evaluate the performance and speed of matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) when identifying the pathogenic microorganism of endophthalmitis compared to conventional microbiological culturing.Methods: Forty-four patients with suspected endophthalmitis who had undergone vitrectomy were enrolled. Vitreous specimen was analyzed using either conventional culturing or MALDI-TOF MS.Results: The identification rates of the conventional microbiological culture and MALDI-TOF MS were 45.5% (20/44) and 65.9% (29/44), respectively (Kappa value 0.787, P < 0.000). The mean detection times by the standard culturing method and MALDI-TOF MS were 5.39 ± 0.56d and 3.17 ± 0.40d (P < 0.001). The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of MALDI-TOF MS were 70.59%, 54.17%, 80.00%, and 86.67%, respectively. Polymicrobial endophthalmitis was identified in 6.82% of the patients (3/44) using conventional microbiological culturing. However, MALDI-TOF MS failed to identify any polymicrobial infection.Conclusions: With a higher sensitivity, acceptable specificity and a shorter detection time, MALDI-TOF MS was an efficient technique for the rapid identification of a pathogenic microorganism in endophthalmitis.

Expression of CCL2 and its receptor in activation and migration of microglia and monocytes induced by photoreceptor apoptosis.

Purpose: To explore the effect of the CCL2 and CCR2 system on the activation and migration of microglia and monocytes in light-induced photoreceptor apoptosis. Methods: At 1 day, 3 days, 7 days, and 14 days after light exposure, OX42 and ED1 immunostaining were used to label the activation and migration of microglia and monocytes. Double immunostaining of CCL2 with terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL), OX42, or glial fibrillary acidic protein (GFAP) was applied to explore the relationships among CCL2, apoptotic photoreceptors, activated microglia and monocytes, and macroglial cells (Müller cells and astrocytes). Real-time PCR was used to evaluate the mRNA levels of retinal CCL2 and CCR2 and the proinflammatory factors interleukin (IL)-1 beta and tumor necrosis factor (TNF)-alpha. Results: Real-time PCR analyses showed that CCL2 and CCR2 expression gradually increased after light exposure and peaked at 3 days, coinciding with the infiltration of OX42-positive cells and the expression of IL-1 beta and TNF-alpha in the outer retina. Double immunostaining of CCL2 with TUNEL revealed that CCL2 was expressed robustly in about 30% of the apoptotic photoreceptors at the early stage. As degeneration progressed, immunostaining of CCL2 with OX42 showed that activated and migrated microglia and monocytes expressed CCL2. At the late stage, Müller cells became the main source of CCL2, which was illustrated by CCL2 immunostaining with GFAP. Conclusions: Light exposure led to apoptosis of photoreceptors, which expressed CCL2, accelerating an inflammation-mediated cascade by activating and attracting microglia and monocytes and promoting their secretion of CCL2 in the injured position.

Evaluation of Retinal Nerve Fiber Layer and Ganglion Cell Complex in Patients with Optic Neuritis or Neuromyelitis Optica Spectrum Disorders Using Optical Coherence Tomography in a Chinese Cohort.

We evaluate a cohort of optic neuritis and neuromyelitis optica (NMO) spectrum disorders patients in a territory hospital in China. The peripapillary retinal nerve fiber layer (RNFL) and macular ganglion cell complex (GCC) were measured using spectral-domain OCT after 6 months of acute onset. The results showed that both the peripapillary RNFL and macular GCC were significantly thinner in all optic neuritis subtypes compared to controls. In addition, the recurrent optic neuritis and NMO groups showed more severe damage on the RNFL and GCC pattern.