Min Wang

Familial amyloid polyneuropathy (FAP) caused by a genetic mutation in transthyretin (TTR) is an autosomal dominant hereditary disease. The retrospective, observational case series study presents the ocular clinicopathological findings of five cases carrying the TTR mutation c.401A>G (p.Tyr134Cys). Multimodal retinal imaging and electrophysiological examination, Congo red staining and immunohistochemical analysis of specimens, and genetic analyses were performed. Cases 1 and 2 were symptomatic with vitreous and retinal amyloid deposition and poor visual recovery. Case 3 had a symptomatic vitreous haze in the left eye with good postoperative visual recovery. The right eye of case 3 and the eyes of cases 4 and 5 were asymptomatic. Thicker retinal nerve fiber layer, retinal venous tortuosity with prolonged arteriovenous passage time on fluorescein angiography and retinal dysfunction detected by multifocal electroretinogram occurred even in asymptomatic eyes. Moreover, the internal limiting membrane from patients with FAP was stained positive for Congo red and transforming growth factor-β1. The results highlight the amyloid deposition of mutant TTR in the optic disc and retina, even in the asymptomatic stage. The deposited amyloid leads to increased resistance to venous return and retinal functional abnormalities. Therefore, careful follow-up of structural and functional changes in the retina is needed, even in asymptomatic patients with FAP.

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.

Objective To compare the retinal vascular network and structure of optic neuritis associated with myelin oligodendrocyte glycoprotein antibodies (MOG-ON) or aquaporin-4 antibodies (AQP4-ON). Methods Nineteen patients with MOG-ON (29 eyes), 24 patients with AQP4-ON (43 eyes), and 25 healthy participants (50 eyes) were enrolled. The best-corrected visual acuity (BCVA), mean deviation (MD), retinal nerve fiber layer (RNFL) thickness, parafoveal ganglion cell and inner plexiform layer (GCIPL) thickness, and vessel densities in the peripapillary and parafoveal areas were measured. Results The BCVA, RNFL thickness, GCIPL thickness, and vessel densities in the peripapillary and parafoveal areas were significantly decreased in the AQP4-ON and MOG-ON eyes compared with healthy controls (all P < 0.05). There were no significant differences in the MD, RNFL thickness, GCIPL thickness, or vessel densities between the AQP4-ON and MOG-ON eyes (all P > 0.05). However, the BCVA was significantly worse in AQP4-ON eyes than in MOG-ON eyes (P = 0.001). The peripapillary vessel density was significantly correlated with the BCVA and MD in AQP4-ON eyes and with MD in MOG-ON eyes (all P < 0.05). Conclusions MOG-ON and AQP4-ON are associated with severe visual dysfunction, as well as retinal structural and vascular damage. The extent of visual dysfunction was strongly correlated with the peripapillary vessel density. Although we found no significant difference in the MD between MOG-ON and AQP4-ON, which are characterized by comparable vascular and structural damage within the peripapillary and parafoveal areas, the BCVA was worse in AQP4-ON eyes than in MOG-ON eyes.

To investigate the longitudinal microstructural and microvascular changes in patients with myelin oligodendrocyte glycoprotein antibody-associated optic neuritis (MOG-ON) without new attacks.We inc...

Background: To determine retinal vessel density in patients with myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD). Methods: Twenty-five patients with MOGAD and 20 healthy participants were enrolled. Patients with MOGAD were divided into myelin oligodendrocyte glycoprotein antibody (MOG-Ab)-positive eyes with a history of optic neuritis (ON; MOG-Ab-ON+ group) or without a history of ON (MOG-Ab-ON− group). Visual function, retinal vessel densities, and thickness were measured. Results: The retinal nerve fiber layer, parafoveal ganglion cell and inner plexiform layers, and vessel densities in the peripapillary and parafoveal areas were significantly decreased in the MOG-Ab-ON+ eyes compared with healthy eyes and MOG-Ab-ON− eyes (all P < 0.05). An increasing number of ON episodes was associated with greater decreases in these variables (all P < 0.05). Visual field mean deviation was not significantly decreased in patients with a history of 1 or 2 episodes of ON, although the relative decreases in retinal nerve fiber layer thickness, parafoveal ganglion cell and inner plexiform layer thickness, peripapillary vessel density, and parafoveal vessel density reached 33.1%, 23.2%, 17.0%, and 11.5% (all P < 0.05), respectively, in eyes with 2 episodes of ON. The mean deviation was significantly correlated with peripapillary vessel density (P < 0.05) after adjustment for other variables. Best-corrected visual acuity was not significantly correlated with optical coherence tomography variables (all P > 0.05). Conclusions: MOG-Ab-associated ON was associated with significant decreases in retinal structure and vessel density, without significant deteriorations in visual function. The peripapillary vessel density might predict the visual outcomes in patients with MOG-Ab-associated ON.

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.

Purpose: This study aimed to develop an automated system with artificial intelligence algorithms to comprehensively identify pathologic retinal cases and make urgent referrals. Methods: To build and test the intelligent system, this study obtained 28,664 optical coherence tomography (OCT) images from 2254 patients in the Eye and ENT Hospital of Fudan University (EENT Hospital) and Shanghai Tenth People's Hospital (TENTH Hospital). We applied a deep learning model with an adapted feature pyramid network to detect 15 categories of retinal pathologies from OCT images as common signs of various retinal diseases. Subsequently, the pathologies detected in the OCT images and thickness features extracted from retinal thickness measurements were combined for urgent referral using the random forest tool. Results: The retinal pathologies detection model had a sensitivity of 96.39% and specificity of 98.91% from the EENT Hospital test dataset, whereas those from the TENTH Hospital test dataset were 94.89% and 98.76%, respectively. The urgent referral model achieved accuracies of 98.12% and 98.01% from the EENT Hospital and TENTH Hospital test datasets, respectively. Conclusions: An intelligent system capable of automatically identifying pathologic retinal cases and offering urgent referrals was developed and demonstrated reliable performance with high sensitivity, specificity, and accuracy. Translational Relevance: This intelligent system has great value and practicability in communities where exist increasing cases of retinal disease and a lack of ophthalmologists.

Purpose: We aim to reveal the disease-causing mutations in 15 Chinese families with optic atrophy (OA). Methods: In total, 15 families with OA were recruited in the present study. Medical histories were carefully reviewed and comprehensive ophthalmic examinations were received by all recruited patients. Targeted next-generation sequencing (NGS) was selectively performed on all probands for mutation detection. Intrafamilial cosegregation and in-silico analyses were subsequently applied to predict the potential pathogenic effects of identified mutations. Results: All included patients presented bilateral vision loss. Their fundus photographs showed temporal or total pallor of the optic discs. Fourteen mutations in the optic atrophy 1 (OPA1) gene were revealed as disease-causing mutations for the 15 families, including eight novel (c.968A>G, c.193C>G, c.1071dupT, c.987_988del, c.2012+2T>G, c.1036-1G>C, c.2126A>G, and c.1036_1038del) and six recurrent (c.1499G>A, c.1800C>A, c.1034G>A, c.2873_2876del, c.112C>T, and c.804_805del) mutations. Conclusions: In conclusion, our study expands the mutational spectrum for the OPAL gene and implies targeted NGS as an effective approach for the genetic diagnosis of OA, which might help to improve the clinical diagnosis for patients with OA.

Giant cell arteritis (GCA) is a systemic vasculitis of medium and large-size vessels and can led to permanent visual loss in elderly patients. GCA is very rare among Asians. We report a Chinese patient presenting with acute bilateral anterior ischemic optic neuropathy, and the temporal artery biopsy proved the diagnose of GCA. A 77-year-old Chinese man presented with sudden bilateral blindness for 5 days with a severe headache. Funduscopic examination revealed bilateral optic disc swollen with “chalky white” pallid appearance. The blood tests showed the erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) elevated dramatically. The color duplex ultrasonography (CDUS) of the superficial temporal artery revealed the inflammation of the vessel wall as a “halo sign”. The temporal artery biopsy was perfumed and the pathology revealed luminal occlusion with multinuclear giant cell infiltration. The patient was treated with intravenous methylprednisolone for 3 days and oral prednisone weaning for 12 months. The visual acuity remained no light perception at one year follow-up. Although very rare in Asian, GCA can led to permanent blindness in elderly Chinese caused by anterior ischemic optic neuropathy. The noninvasive CDUS might be a promising technique for diagnose GCA in highly suspected patients.