Currently, coronavirus disease 2019 (COVID-19) is still widely prevalent around the world, leading to a major threat to the global public health. COVID-19 mainly involves the respiratory system, but extrapulmonary manifestations including that of the nervous system also exist in the setting of COVID-19. Misdiagnosis and delayed treatment of the disease may easily cause when ocular, especially neuro-ophthalmological symptoms are the first symptoms in early COVID-19, as the neuroophthalmological manifestations are rarely reported. First-line clinicians need to ask about not only respiratory symptoms such as fever, cough and sore throat, but also diplopia, impaired vision, eye motion pain, abnormal gait or other neurological deficits at the first reception, as these extrapulmonary manifestations are often signs of serious infection. The neuroophthalmological manifestations and possible underlying etiology of COVID-19 were summarized in this review, hoping to provide an early identification and effective treatment of COVID-19 for clinicians. More extensive studies are needed in the future to confirm the causal relationship between COVID-19 and neuroophthalmological disease to provide a sufficient basis for a comprehensive understanding of COVID-19. Copyright © 2021 by the Chinese Medical Association.

Objective To investigate the clinical, laboratory and imaging evaluation, treatment and prognosis of patients with idiopathic hypertrophic pachymeningitis (IHP) with ophthalmic manifestations as the first symptom. Methods A retrospective case analysis. Eight patients displaying symptoms of IHP were recruited from the Neuro-ophthalmology Department in the First Medical Center of Chinese PLA General Hospital from January 2016 to April 2019 were inculed in this study. There were 6 males and 2 females, aged from 11 to 65 years, with an average age of 48.00±19.08 years. The course of disease ranged from 30 days to 7.5 years, with an average course of 17.00±30.08 months. The age, symptoms and signs of all patients were recorded. All patients underwent ophthalmic examination, orbit or brain MRI or CT examinations, blood routine examination, biochemistry, tumor markers, immunity, hepatitis B, syphilis, HIV, thyroid function and other laboratory tests, and lumbar puncture was performed to measure the cerebrospinal fluid (CSF) pressure and indicators. The clinical manifestations, orbital or brain MRI imaging and laboratory examination characteristics were summarized. Treatment and prognosis were also observed. Results In total of 8 patients, visual loss was presented in 6 patients, visual loss and diplopia were presented in 1 patient, and diplopia was presented in 1patient. Binocular involvement in 7 patients and monocular involvement in 1 patient. Other symptoms including headache and hear loss and so on. Optic disc edema in 1 eye and optic disc pallor in 6 eyes were reviewed by fundus examination. The laboratory examination showed that the angiotensin converting enzyme abnormal in 4 patients, the anti-thyroid peroxidase antibody abnormal in 3 patients and immunoantibodies positive in 3 patients. CSF measurements showed that the protein level elevated in all patients. Orbit and/or brain MRI and CT examination showed that optic nerve involvement in 6 patients, oculomotor nerve involvement in 1 patient, and cavernous sinus region involvement in 2 patients. Glucocorticoid was effective in all patients, and the visual acuity significantly improved in 4 patients, the diplopia was completely resolved in 2 patients, and the disease modifying therapy (DMT) was combined to prevent recurrence in 7 patients. No recurrence was observed in an average follow-up time of 26.63±16.55 months. Conclusions IHP patients may be first visit an ophthalmologist due to vision loss in bilateral eyes simultaneous or sequentially. IHP patients are often associated with headache and other cranial nerve paralysis symptoms. Definitive diagnosis of IHP depends on imaging examination. Glucocorticoid treatment is effective in early phase, but it is tendency to progress and relapse, suggesting combined with DMT as early as possible. Key words: Meningitis; Vision, low; Diplopia; Glucocorticoids; Disease modifying therapy

Objective To observe the clinical, radiographic features and prognosis of aquaporin-4 antibody positive pediatric optic neuritis (AQP4-PON). Methods A retrospective case series. Twenty-three eyes of 14 children with AQP4-PON who were clinically confirmed in the Department of Ophthalmology of the First Medical Center of the Chinese PLA General Hospital from January 2015 to December 2018 were included in the study. All patients underwent BCVA, fundus color photography, and magnetic resonance imaging (MRI). OCT was performed on 15 eyes of 10 patients, and the peripapillary retinal nerve fiber layers (pRNFL), macular ganglion cell-inner plexiform layers (mGCIPL) thickness of the affected eyes were measured. Cell-based indirect fluorescent immunoassay was used to detect serum AQP4 antibodies and myelin oligodendrocyte glycoprotein antibodies. The follow-up time ranged from 28 to 59 months. The clinical, neuroimaging characteristics and prognosis of the children were analyzed. Results Among 14 children, 2 were male (14.3%) and 12 were female(85.7%). The mean age of onset was 13.3±3.0 years. On the first visit, there were 10 unilateral patients and 4 bilateral patients. The first manifestations were 11 patients of optic neuritis (78.6%), 2 patients of posterior pole syndrome (14.3%), and 1 patient of myelitis (7.1%). There were 10 patients (71.4%) with eye pain, and 5 patients(35.7%) combined with autoantibodies positive. When the first onset time was less than 2 weeks, fundus examination revealed disc edema in 7 eyes (38.9%). After 3 months, the average pRNFL and mGCIPL thickness of 15 eyes underwent OCT examination were 62.33±11.07 and 54.17±5.42 μm, respectively. Orbital MRI showed that the optic nerve showed a long T2 signal in 14 patients (100.0%) and 11 patients (78.6%) with T1 intensive lesions. When the first onset was less than 2 weeks, 16 eyes (88.9%) had BCVA≤0.1, and 7 eyes(38.9%) had BCVA≤0.1 and 9 eyes (50.0%) with BCVA≥0.5 after glucocorticoid treatment. Recurrence occurred in 11 patients during follow-up and was treated with immunosuppressive agents. At the last visit, in 14 patients, 9 eyes (64.3%) were involved in both eyes, and 5 patients (35.7%) progressed to neuromyelitis optica; in 23 eyes, 8 eyes (34.8%) had BCVA≥0.5. Conclusions AQP4-PON patients are more common in women, severely impaired visual function, easy to relapse, and some patients will progress to neuromyelitis optica. Key words: Aquaporin 4; Optic neuritis; Neuromyelitis optica; Child

Objective To observe the macular vascular density and the area of foveal avascular zone(FAZ) in the follow eyes of monocular retinal vein occlusion (RVO) patients. Methods Retrospective case-control study. From May to November 2018, 78 follow eyes of 78 monocular RVO patients who were clinically diagnosed in Changsha Aier Eye Hospital were included in the study. Among them, 44 were male and 34 were female. The average age was 53.17±10.12 years. There were 42 patients with central retinal vein occlusion(CRVO group) and 36 patients with branch retinal vein occlusion (BRVO group). Forty-two eyes of 33 gender and age matched healthy volunteers were selected as the control group. Among them, 17 were male (22 eyes) and 16 were female (20 eyes), with the mean age of 53.48±10.84 years. OCT angiography was performed on all eyes in CRVO group, BRVO group and control group. The scanning region in the macular area was 6 mm× 6 mm. Macular vascular density and FAZ area in the superficial and deep retinal capillary plexi were measured. Results The mean overall vascular density measured in the entire scan was lower in the CRVO group(t=-4.26, -4.93) and BRVO group (t=-4.79, -4.74) compared with the control group in both the superficial and deep capillary plexus (P 0.05). Conclusions The macular vascular density in the follow eyes of monocular RVO patients is lower than that of normal healthy eyes. The reduce degree of vascular density in the deep capillary plexus is higher than that in the superficial plexus. Compared with normal healthy eyes, the FAZ area in the follow eyes of monocular CRVO patients decreased, while it did not change significantly in the follow eyes of monocular BRVO patients. Key words: Retinal vein occlusion; Regional blood flow; Tomographyoptical coherence

Objective To observe the protective effect of Zhicao Tea Mixture on Muller cells and the expression of inflammatory factors in mice with diabetic retinopathy. Methods Seventy-five C57BL/6J mice were randomly divided into the normal control group, diabetes mellitus (DM) group, low concentrations group, medium concentrations group and high concentrations group, with 16 mice in each group. The diabetes model of mice in all groups except the normal control group were established by intraperitoneal injection of STZ (60 mg/kg). Four weeks after the successful modeling, the Zhicao Tea Mixture with low (30 ml/kg), medium (60 ml/kg) and high concentrations (120 ml/kg) were respectively administered by gavage. Weight and blood glucose of mice in each group were measured every two weeks. After 8 weeks, Western blot method was used to detect the mice retina Muller cells activation marker gelatinous fibrous acidic protein (GFAP). Immunofluorescence was performed to detect the expression GFAP and glutamine synthetase (GS). Real-time quantitative PCR (RT- qPCR) and ELISA were used to determine the mRNA and protein expression levels of mouse retinal VEGF, TNF-α, IL-1β and IL-6 respectively. Results The weight of mice in the DM group was lower than that of the normal control group, and the blood glucose was increased. Zhicao Tea Mixture had no effect on the weight of DM mice, but had a significant hypoglycemic effect. The GFAP expression (t=38.318, P<0.001) in the retina of mice in the DM group was increased and GS expression (t=29.737, P<0.001) was decreased compared with the control group. The GFAP expression (t=13.677, 19.387, 16.305; P<0.05) in the retina of mice in the low, medium and high concentrations group were decreased and GS expression (t=5.170, 19.399, 6.705; P<0.05) were increased compared with the DM group. The expressions of retinal inflammatory factors VEGF, TNF-α, IL-1β and IL-6 in DM group all increased, while the expressions of the above-mentioned inflammatory factors in the retina of mice decreased in the low, medium and high concentrations group. Conclusion Zhicao Tea Mixture can decrease the blood glucose of DM mice and reduces the diabetic retinal inflammatory response. Key words: Diabetic retinopathy/physiopathology; Inflammation; Muller cells; Zhicao Tea Mixture

Objective To observe the clinical features and visual prognostic factors of ethambutol-induced optic neuropathy (EON). Methods A cohort study. Twenty-four inpatients (46 eyes) identified as EON in Neuro-Ophthalmology Department of Chinese PLA General Hospital from January 2014 to December 2017 were enrolled, including 14 males (26 eyes) and 10 females (20 eyes) with a ratio of 1.4/1 male/female. The average age was 42.79±15.12 years and the average weight was 62.46±12.31 kg. The average time duration between oral administration of ethambutol and occurrence of EON was 9.94±16.49 months. The average time of ethambutol duration was 7.06±11.68 months, with an average accumulative dose of 156.7±1 779.0 g and the average daily dose of 15.07±8.95 mg/(kg·d). All patients were tested with visual acuity, fundus photos, colour vision, OCT, visual field, VEP, orbital MRI and the gene of OPA1 and mitochondrial deoxyribonucleic acid(mtDNA). All the patients accepted drug withdrawal immediately after diagnosis, and were given the treatment of systemic nerve nutrition and improvement of microcirculation for 2 weeks. The time of follow-up was more than 12 months. According to whether the visual acuity (VA) in any of eyes was over than 0.1 at the last follow- up, all the patients were divided into two groups: the bad VA group (VA less than or equal to 0.1) and the better VA group (VA over than 0.1) group. The χ2 test and Fisher's exact probabilistic method test were used to compare the counting data between groups, and the Wlincox rank sum test was used to compare the measurement data. Multiple factors of VA outcome between the patients with bad or better va were analyzed by logistic regression. Results Thirty eyes (65.2%) had VA less than or equal to 0.1 and 5 eyes (10.9%) had VA over than 0.5 at EON onset. The VA of the rest 11 eyes (23.9%) was higher than 0.1 and lower than 0.5. At the last follow- up, 20 eyes (43.5%) had VA less than or equal to 0.1 and 9 eyes (19.6%) had VA over than 0.5, the VA of the rest 17 eyes (36.9%) was higher than 0.1 and lower than 0.5. Fundus examination revealed 7 eyes (15.3%) with optic disc edema. OCT revealed significant loss of the retinal nerve fiber layer (RNFL) in the affected eyes, mainly in the temporal RNFL of the optic disc. All patients had dyschromasia, mainly in distinguishing the color of red and green. The types of visual field defect was as following: central dark spot (52.2%), diffuse visual acuity decreased (30.4%), temporal hemianopsia (17.4%). Orbital MRI revealed that 12/24 (50.0%) patients had T2 lesions with T1 enhancement in 6/24 patients (25.0%). Genetic test showed that 4 patients (16.7%) had gene mutation. Among them, there were 2 patients with OPA1 mutation, 1 with mtDNA 14340 point mutation and 1 with the mtDNA 11778 point mutation. Thirteen patients showed better VA outcomes (over than 0.1) while 11 showed bad VA outcomes after discontinuation of ethambutol. Between the better VA group and the bad VA group, there were statistically significant differences in the daily dose of ethambutol and gene mutation(P=0.031, 0.023). The daily dose was related to visual prognosis of EON while only the daily dose of more than 18 mg/(kg·d) may lead to bad VA outcomes according to the logistic analysis (95% CI 0.007-0.736, OR=0.069, P=0.027). Conclusions EON may have OPA1 and mtDNA mutation with more bilateral eyes involved and less optic edema, which about 43.5% of the patients showed irreversible visual impact. The daily dose of ethambutol is related to the vision recovery. Key words: Ethambutol/adverse effects; Optic nerve diseases; Disease attributes; Prognosis; Root cause analysis

Objective To evaluate the efficacy and safety of reduced-dose intravitreal ganciclovir for the treatment of acquired immunodeficiency syndrome (AIDS) patients with cytomegalovirus retinitis (CMVR). Methods A prospective observational cohort study observed 15 AIDS patients (28 eyes) who suffered from CMVR onset between January 2016 and December 2018 at Nanning Aier Eye Hospital. Among this 28 eyes, BCVA of 6 eyes (21.4%) were between moving hand to counting finger, 15 eyes (53.6%) were between 0.02 to 0.1 and 7 eyes were better than 0.1 (25.0%). All eyes received intravitreal injection 0.1 ml of ganciclovir at 4 mg/ml (contain ganciclovir 0.4 mg). The induction regimen was twice weekly for 2 weeks and a maintenance period of the same dose weekly. The mean number of injections was 7.1±1.7 times. For hospitalized patients who had no contraindicated received a 14-day twice daily intravenous ganciclovir (IVG) 5.0 mg/kg·d until complete resolution of CMVR. All patients were divided into intravitreal ganciclovir (IVTG) group and IVTG+IVG group according to different treatment plans, which were 5 cases with 8 eyes and 10 cases with 20 eyes, respectively. The follow-up was more than 6 months. BCVA, complete resolution or stable of the lesion and complications were observed. Results Six months later, 20 eyes (71.4%) had a obvious reduced or disappeared of the anterior chamber and vitreous inflammation, and the retinal lesions became stable or complete resolution. 24 eyes showed improvements of BCVA and 4 eyes showed stable. 2 eyes (7.1%) presented with BCVA ≤ counting finger, 7 eyes (25.0%) were 0.02- 0.1 and 19 eyes were ≥ 0.1 (67.9%). Compared with before treatment, the ratio of BCVA that less than or equal to counting finger and between 0.02 to 0.1 decreased(21.4% vs 7.1% and 53.6% vs 25.0%, respectively), but the ratio of BCVA better than 0.1 increased (25.0% vs 67.9%). When IVTG+IVG group was compared with IVTG group, the average time-to-resolution of CMVR were 83.2±25.2 and 85.3±24.4 days respectively. There was no significant difference in resolution times(Z=0.17, P=0.87). The ratio of retinal lesions became stable or complete resolution were 75.0% (15 eyes) and 62.5% (5 eyes), there was no evident difference in time-to-resolution between the two groups (F=0.42, P=0.51). No recurrence was seen during the follow-up period. In cases of unilateral CMVR, there were no patients with a second eye involvement during the follow-up period. No endophthalmitis, vitreous hemorrhage, retinal detachment were found in our study. Conclusion Reduced-dose intravitreal ganciclovir is a safe and effective treatment option for CMVR. Key words: Acquired immunodeficiency syndrome/complications; Cytomegalovirus retinitis/drug therapy; Ganciclovir/therapeutic use; Treatment outcome

Central nervous system vascular disease can be combined with a variety of ocular signs, such as orbital pain, flash, visual field defects, vision loss, eye muscle paralysis. Therefore, some patients were first diagnosed in ophthalmology, including aneurysm rupture, arterial dissection, cerebral apoplexy and other critical nervous system diseases that need rapid treatment. If the doctors didn't know enough, the diagnosis and treatment might be delayed. Most of the vascular diseases of the central nervous system related to ophthalmology have clinical manifestations that cannot be explained by ophthalmology. In the face of chronic conjunctivitis, unexplained visual field defect or cranial nerve paralysis with local ineffective treatment, it is necessary to broaden the thinking of differential diagnosis. To understand the characteristics of vascular diseases of the central nervous system that are prone to ocular manifestations can provide references for the clinical diagnosis and treatment of ophthalmology. Key words: Central nervous system diseases; Intracranial aneurysm; Carotid-cavernous sinus fistula; Intracranial hypertension; Review

Objective To investigate the protective effects of different concentrations of chloroquine on RGC in n-methyl-d-aspartate (NMDA) injured mice and its possible mechanisms. Methods Fifty-four healthy male C57/BL6 mice were randomly divided into three groups, 18 in each group. The mice in low-dose chloroquine group were intraperitoneally injected with chloroquine solution at a dose of 10 mg/kg daily. Mice in high-dose chloroquine group were intraperitoneally injected with chloroquine solution at a dose of 100 mg/kg, and the mice in control group were intraperitoneally injected with the same volume of PBS. NMDA intravitreal injection was performed 2 days after intraperitoneal injection, 5 nmoles NMDA was injected into the left eye, and the same volume of PBS was injected into the right eye as a control. The RGC staining of retinal plaques were performed 7 days after NMDA injection, and the number of alive RGC was calculated. The visual acuity and electroretinogram were used to evaluate the electrophysiological functions of RGC at 9 and 10 days after modeling. Real-time quantitative PCR and retinal frozen sections and glial fibrillary acidic protein (GFAP) immunofluorescence staining were performed 11 days after NMDA injection to evaluate the glial activation of the retina. The density, visual acuity, and the amplitude of PhNR-wave of RGC between groups were compared by one-way analysis of variance. Results At 7 days after NMDA injection, the density of RGC in retinal patch of low-dose chloroquine group was significantly higher than that of intraperitoneal injection of PBS control group (F=54.41, P 0.05). The visual acuity was higher than control group, and the difference was statistically significant (F=9.10, P<0.05). The amplitude of PhNR-wave was significantly higher in low-dose chloroquine group than that of the control group (F=17.60, P<0.01). The mRNA level of inflammatory factor and GFAP positive signal was also significantly lower than that of the control group (F=23.66, P<0.05). The amplitude of PhNR-wave, the expression of GFAP (F=110.20, P<0.01) and the mRNA level of inflammatory factors (F=167.60, 17.78; P<0.01) in the high-dose chloroquine group were higher than the other two groups, and the differences were statistically significant. Conclusions In NMDA injury retinal model, low-dose chloroquine significantly increased the survival and physiological function of RGC, and the mechanism may be related to the inhibition of glial activation and inflammatory response. High-dose of chloroquine would aggravate the apoptosis of RGC. Key words: Chloroquine; Retinal ganglion cells; N-methylaspartate; Toxic actions; Animal experimentation

Choroidal neovascularization is the leading causes of central vision loss in wet age-related macular degeneration (wAMD) patients. Smoking not only aggravates the incidence and severity of the choroidal neovascularization of wAMD, but also affects the clinical treatment, making the prognosis worse. Nicotine, as an important harmful substance in tobacco, is an easily addictive and highly toxic alkaloid. Animal experiments and clinical studies have confirmed that nicotine can aggravate wAMD by mediating angiogenesis through nicotinic acetylcholine receptor, bone marrow blasts, inflammation, complement system, etc. Therefore, in order to early take appropriate intervention measures to prevent and delay the development, we should actively explore the exact pathogenesis by which nicotine aggravates the choroidal neovascularization. Key words: Wet macular degeneration/etiology; Choroidal neovascularization/etiology; Nicotine; Review