Macular thickness as a predictor of loss of visual sensitivity in ethambutol-induced optic neuropathy

Ethambutol is a common cause of drug-related optic neuropathy.Prediction of the onset of ethambutol-induced optic neuropathy and consequent drug withdrawal may be an effective method to stop visual loss.Previous studies have shown that structural injury to the optic nerve occurred earlier than the damage to visual function.Therefore,we decided to detect structural biomarkers marking visual field loss in early stage ethambutol-induced optic neuropathy.The thickness of peripapillary retinal nerve fiber layer,macular thickness and visual sensitivity loss would be observed in 11 ethambutol-induced optic neuropathy patients（22 eyes） using optical coherence tomography.Twenty-four healthy age-and sex-matched participants（48 eyes） were used as controls.Results demonstrated that the temporal peripapillary retinal nerve fiber layer thickness and average macular thickness were thinner in patients with ethambutol-induced optic neuropathy compared with healthy controls.The average macular thickness was strongly positively correlated with central visual sensitivity loss（r2=0.878,P=0.000）.These findings suggest that optical coherence tomography can be used to efficiently screen patients.Macular thickness loss could be a potential factor for predicting the onset of ethambutol-induced optic neuropathy.

Ethambutol-induced optic neuropathy with rare bilateral asymmetry onset:A case report

BACKGROUND Ethambutol-induced optic neuropathy(EON)most commonly manifests as bilateral symmetrical loss of vision and often cause serious and irreversible visual impairment because of the lack of early detection and effective treatment.We followed a case of EON with rare binocular asymmetric clinical manifestations and observed the changes of visual function and retinal structure after drug withdrawal,so as to further understand the clinical characteristics of this disease.CASE SUMMARY A 54-year-old man complained of gradual visual decline in the left eye.The patient presented with best-corrected visual acuity of 20/20 in the right eye and 20/50 in the left eye.Color vision examination revealed difficulty in reading green color plates in the left eye.The visual field manifested as concentric contraction in the left eye.After nearly a month of drug withdrawal,the right eye had a similar decline in visual function.At the last visit,19 mo after drug withdrawal,the visual function significantly recovered in both eyes.During follow-up optical coherence tomography(OCT)examination,both eyes manifested the thickness of the retinal nerve fiber layer from mild thickening to thinning and finally temporal atrophy,and the ganglion cell-inner plexiform layer showed significant thinning.The difference was that a reversible structural disorder in the outer retina of the nasal macula was detected in the left eye by macular high-definition OCT.CONCLUSION Nephropathy and high blood pressure,which damage the retinal microcirculation,may cause damage to the outer layer of the retina.Ethambutol may influence photoreceptor as well as retinal ganglion cells.

A Prediction Model for Detecting Dysthyroid Optic Neuropathy Based on Clinical Factors and Imaging Markers of the Optic Nerve and Cerebrospinal Fluid in the Optic Nerve Sheath

Objective This study aimed to develop and test a model for predicting dysthyroid optic neuropathy(DON)based on clinical factors and imaging markers of the optic nerve and cerebrospinal fluid(CSF)in the optic nerve sheath.Methods This retrospective study included patients with thyroid-associated ophthalmopathy(TAO)without DON and patients with TAO accompanied by DON at our hospital.The imaging markers of the optic nerve and CSF in the optic nerve sheath were measured on the water-fat images of each patient and,together with clinical factors,were screened by Least absolute shrinkage and selection operator.Subsequently,we constructed a prediction model using multivariate logistic regression.The accuracy of the model was verified using receiver operating characteristic curve analysis.Results In total,80 orbits from 44 DON patients and 90 orbits from 45 TAO patients were included in our study.Two variables(optic nerve subarachnoid space and the volume of the CSF in the optic nerve sheath)were found to be independent predictive factors and were included in the prediction model.In the development cohort,the mean area under the curve(AUC)was 0.994,with a sensitivity of 0.944,specificity of 0.967,and accuracy of 0.901.Moreover,in the validation cohort,the AUC was 0.960,the sensitivity was 0.889,the specificity was 0.893,and the accuracy was 0.890.Conclusions A combined model was developed using imaging data of the optic nerve and CSF in the optic nerve sheath,serving as a noninvasive potential tool to predict DON.

Risk factors of non-arteritic anterior ischaemic optic neuropathy and central retinal artery occlusion

AIM:To investigate the difference in risk factors between non-arteritic anterior ischaemic optic neuropathy(NAION)and central retinal artery occlusion(CRAO)and develop a predictive diagnostic nomogram.METHODS:The study included 37 patients with monocular NAION,20 with monocular CRAO,and 24 with hypertension.Gender,age,and systemic diseases were recorded.Blood routine,lipids,hemorheology,carotid and brachial artery doppler ultrasound,and echocardiography were collected.The optic disc area,cup area,and cup-to-disc ratio(C/D)of the unaffected eye in the NAION and CRAO group and the right eye in the hypertension group were measured.RESULTS:The carotid artery intimal medial thickness(C-IMT)of the affected side of the CRAO group was thicker(P=0.039)and its flow-mediated dilation(FMD)was lower(P=0.049)than the NAION group.Compared with hypertension patients,NAION patients had higher whole blood reduced viscosity low-shear(WBRV-L)and erythrocyte aggregation index(EAI;P=0.045,0.037),and CRAO patients had higher index of rigidity of erythrocyte(IR)and erythrocyte deformation index(EDI;P=0.004,0.001).The optic cup and the C/D of the NAION group were smaller than the other two groups(P<0.0001).The diagnostic prediction model showed high diagnostic specificity(83.7%)and sensitivity(85.6%),which was highly related to hypertension,the C-IMT of the affected side,FMD,platelet(PLT),EAI,and C/D.CONCLUSION:CRAO patients show thicker C-IMT and worse endothelial function than NAION.NAION and CRAO may be related to abnormal hemorheology.A small cup and small C/D may be involved in NAION.The diagnostic nomogram can be used to preliminarily identify NAION and CRAO.

Evaluation of Clinical Efficacy of Wumen Acupuncture in the Adju-vant Treatment of Non-arteriticAnterior Ischemic Optic Neuropathy

[Objectives]To explore the clinical efficacy of Wumen acupuncture in the adjuvant treatment of non-arteritic anterior ischemic op-tic neuropathy(NAION).[Methods]From June 2023 to April 2024,40 NAION patients were randomly divided into treatment group(Wu-men acupuncture method+methylprednisolone sodium succinate+compound Danshen dripping pills orally)and control group(methylpred-nisolone sodium succinate+compound Danshen dripping pills orally).The clinical symptoms such as fundus condition and visual field were compared between the two groups before treatment,after 2 courses of treatment and 6 months after the first diagnosis.[Results](i)After 2 courses of treatment,the patients with optic disc edema in the treatment group were more than those in the control group,and the difference was significant(P<0.05).The number of patients with retinal hemorrhage in the treatment group was less than that in the control group,and the difference was significant(P<0.05).The color of the optic nerve in the treatment group was less than that in the control group,and the difference was not significant(P>0.05).(ii)Six months after the first diagnosis,the improvement of fundus in the treatment group was bet-ter than that in the control group(P<0.05).After 2 courses of treatment and 6 months after the first diagnosis,the visual evoked potential was significantly improved compared with the control group(P<0.05).After 2 courses of treatment and 6 months from the first diagnosis,the number of lines of visual acuity improvement in the treatment group was greater than that in the controlgroup(P<0.05).After 2 courses of treatment and 6 months from the first diagnosis,the average visual field defect in the treatment group was lower than that in the control group(P<0.05).[Conclusions]Wumen acupuncture method can significantly improve the symptoms of patients with non-arteritic anterior ische-mic optic neuropathy,which is worthy of clinical promotion.

Outbreak of methanol-induced optic neuropathy in early COVID-19 era;effectiveness of erythropoietin and methylprednisolone therapy

BACKGROUND Methanol is a highly toxic,non-potable alcohol.Outbreaks of methanol toxicity occur due to its fraudulent addition to alcoholic beverages as a cheaper substitute for ethanol.Recently,alongside the coronavirus disease 2019(COVID-19)pandemic,rumors circulated on social media that consuming alcohol can prevent or cure the virus,leading to a COVID-19 and methanol-induced optic neuropathy(MON)syndemic.AIM To investigate the impact of erythropoietin(EPO)on the outcomes of patients diagnosed with MON.METHODS In this prospective study,105 patients presenting with acute bilateral visual loss secondary to methanol intoxication were enrolled from March to May 2020 at Farabi Eye Hospital.A comprehensive ocular examination was conducted for all participants.Recombinant human EPO and methylprednisolone were administered intravenously to all patients for three consecutive days.RESULTS The mean age of the participants was 39.9 years(±12.6).Ninety-four patients were male and eleven were female.The mean pre-treatment best corrected visual acuity(BCVA)improved from 2.0±0.86 to 1.39±0.69 logarithm of the minimum angle of resolution post-treatment(P<0.001),with significant improvement observed in all age categories and genders(P<0.001).Visual acuity improvement was also significant regardless of whether the patient presented before or after 72 h(P<0.001),and the post-treatment BCVA remained significant at all monthly follow-up visits(P<0.001).CONCLUSION EPO and methylprednisolone therapy have been shown to be effective in improving visual outcomes in patients with MON when administrated within the first month of exposure.Public awareness efforts are necessary to prevent further outbreaks of methanol toxicity in the current COVID-19 era.

Photoreceptor changes in Leber hereditary optic neuropathy with m.G11778A mutation

·AIM:To evaluate the functional and structural changes of photoreceptors in patients and asymptomatic carriers with Leber hereditary optic neuropathy(LHON)using fullfield electroretinography(FERG)and optical coherence tomography(OCT).·METHODS:Individuals diagnosed with LHON at the Renmin Hospital of Wuhan University and their family members were included in this cross-sectional observational study.The FERG a-wave amplitude of affected patients and asymptomatic carriers was analyzed.The thickness of the outer nuclear layer(ONL),inner and outer segment(IS/OS)and total photoreceptors in the macular fovea and parafovea were measured.·RESULTS:This study included 14 LHON patients(mean age:20.00±9.37y),12 asymptomatic carriers(mean age:39.83±6.48y),and 14 normal subjects(mean age:24.20±1.52y).The FERG results showed that the darkadapted 3.0 electroretinography and light-adapted 3.0 electroretinography a-wave amplitudes of patients and carriers were significantly decreased(P<0.001).The ONL and photoreceptors layers were slightly thicker in patients than in normal subjects(P<0.05),whereas they were thinner in carriers(P<0.05).There were no differences in IS/OS thickness among the groups(P>0.05).·CONCLUSION:Photoreceptors function is significantly impaired in LHON-affected patients and asymptomatic carriers.Meanwhile,photoreceptors morphology is slightly altered,mainly manifesting as a change in ONL thickness.

Impact of Selected Processing Methods of High-Level Cyanide in Cassava on Optic Neuropathy in Wistar Albino Rats—An Experimental Study

Background: Cassava tuber crop is a staple food rich in carbohydrates and utilized in various forms by millions of Nigerians. The storage root of the cassava contains linamarin, a cyanogenic glycoside that is easily hydrolyzed to release cyanide salt compounds which is toxic to the nervous system especially the optic nerve, sometimes leading to optic neuropathy and visual impairment. Aim: The aim of this study is to find out the impact of selected processing methods of high-level cyanide in cassava on optic neuropathy in Wistar albino rats. Methodology: Twenty-four Wistar albino rats were fed with different concentration and duration of predetermined high-cyanide content cassava root cultivar which was processed using different processing methods adopted by various communities in Rivers State, Nigeria (for human consumption). A control group of 3 Wistar albino rats was fed with normal “Growth Mesh” meals. The pre and post weights of the animals and the fundoscopic optic nerve status of the rats were evaluated after 30 and 60 days. SPSS Version 25 was employed for descriptive and inferential statistical analyses. A p-value of ≤0.05 was considered statistically significant. Results: The Cassava species available in Rivers State have high cyanide content (2336.79 mg CN-/kg dry weight of cassava). There was statistically significant reduction in the cyanide content (p = 0.000) depending on the various common processing methods (into garri for human consumption): 24 hours, 48 hours, fermentation;with and without red palm oil additive. The individual weights as well as the mean weight of the 24 rats in the experimental group increased gradually from the first week to the 9th week with a slight weight reduction on the third and fourth weeks which was not statistically significant (p = 0.092). However, there was a steady increase in the weights of the animals in the control group throughout the 9 weeks. Varying degrees of optic neuropathy occurred, worse with the rats that had 24-hour fermented cassava twice daily for 60 days. The intra and inter group differences in the optic disc changes was statistically significant (p = 0.000). Conclusion: Longer duration of processing cassava roots into garri for human consumption reduces its cyanide content and minimizes the adverse impact on the optic nerve.

Non-arteritic anterior ischemic optic neuropathy combined with branch retinal vein obstruction:A case report

BACKGROUND Non-arteritic anterior ischemic optic neuropathy(NAION)is an independent disease characterized by edematous optic discs.In eyes with branch retinal vein occlusion(BRVO),the arteries and veins in the ethmoid plate of the optic disc are relatively crowded;however,a combination of the two is clinically uncommon.Herein,we reported a patient with NAION and concealed BRVO,for which the treatment and prognosis were not similar to those for NAION alone.CASE SUMMARY Herein,we report a case of NAION with concealed BRVO that did not improve with oral medication.A week later,we switched to intravenous drug administration to improve circulation,and the patient’s visual acuity and visual field recovered.Hormonal therapy was not administered throughout the study.This case suggested that:(1)Fundus fluorescein angiography(FFA)can help detect hidden BRVO along with the NAION diagnosis;(2)intravenous infusion of drugs to improve circulation has positive effects in treating such patients;and(3)NAION with concealed BRVO may not require systemic hormonal therapy,in contrast with the known treatment for simple NAION.CONCLUSION NAION may be associated with hidden BRVO,which can only be observed on FFA;intravenous therapy has proven effectiveness.

Automated evaluation of parapapillary choroidal microvasculature in crowded optic discs:a controlled,optical coherence tomography angiography study

AIM:To compare superficial and deep vascular properties of optic discs between crowded discs and controls using optical coherence tomography angiography(OCT-A).METHODS:Thirty patients with crowded discs,and 47 control subjects were enrolled in the study.One eye of each individual was included and OCT-A scans of optic discs were obtained in a 4.5×4.5 mm^(2) rectangular area.Radial peripapillary capillary(RPC)density,peripapillary retinal nerve fiber layer(pRNFL)thickness,cup volume,rim area,disc area,cup-to-disc(c/d)area ratio,and vertical c/d ratio were obtained automatically using device software.Automated parapapillary choroidal microvasculature(PPCMv)density was calculated using MATLAB software.When the vertical c/d ratio of the optic disc was absent or small cup,it was considered as a crowded disc.RESULTS:The mean signal strength index of OCT-A images was similar between the crowded discs and control eyes(P=0.740).There was no difference in pRNFL between the two groups(P=0.102).There were no differences in RPC density in whole image(P=0.826)and peripapillary region(P=0.923),but inside disc RPC density was higher in crowded optic discs(P=0.003).The PPCMv density in the inner-hemisuperior region was also lower in crowded discs(P=0.026).The pRNFL thickness was positively correlated with peripapillary RPC density(r=0.498,P<0.001).The inside disc RPC density was negatively correlated with c/d area ratio(r=-0.341,P=0.002).CONCLUSION:The higher inside disc RPC density and lower inner-hemisuperior PPCMv density are found in eyes with crowded optic discs.

Small extracellular vesicles derived from human induced pluripotent stem cell-differentiated neural progenitor cells mitigate retinal ganglion cell degeneration in a mouse model of optic nerve injury

Several studies have found that transplantation of neural progenitor cells(NPCs)promotes the survival of injured neurons.However,a poor integration rate and high risk of tumorigenicity after cell transplantation limits their clinical application.Small extracellular vesicles(sEVs)contain bioactive molecules for neuronal protection and regeneration.Previous studies have shown that stem/progenitor cell-derived sEVs can promote neuronal survival and recovery of neurological function in neurodegenerative eye diseases and other eye diseases.In this study,we intravitreally transplanted sEVs derived from human induced pluripotent stem cells(hiPSCs)and hiPSCs-differentiated NPCs(hiPSC-NPC)in a mouse model of optic nerve crush.Our results show that these intravitreally injected sEVs were ingested by retinal cells,especially those localized in the ganglion cell layer.Treatment with hiPSC-NPC-derived sEVs mitigated optic nerve crush-induced retinal ganglion cell degeneration,and regulated the retinal microenvironment by inhibiting excessive activation of microglia.Component analysis further revealed that hiPSC-NPC derived sEVs transported neuroprotective and anti-inflammatory miRNA cargos to target cells,which had protective effects on RGCs after optic nerve injury.These findings suggest that sEVs derived from hiPSC-NPC are a promising cell-free therapeutic strategy for optic neuropathy.

Structural impairment patterns in peripapillary retinal fiber layer and retinal ganglion cell layer in mitochondrial optic neuropathies

AIM：To evaluate the structural injure patterns in peripapillary retinal fiber layer （pRNFL）, retinal ganglion cell layer （RGCL） and their correlations to visual function in various mitochondrial optic neuropathies （MON） to offer help to their differential diagnosis.METHODS：Totally 32 MON patients （60 eyes） were recruited within 6mo after clinical onsets, including 20 Leber hereditary optic neuropathy （LHON） patients （37eyes）, 12 ethambutol-induced optic neuropathy （EON）patients （23 eyes）, and 41 age-gender matched healthy controls （HC, 82 eyes）. All subjects had pRNFL and RGCL examinations with optic coherence tomography （OCT） and visual function tests.RESULTS：In the early stages of MON, the temporal pRNFL thickness decreased （66.09±22.57μm）, but increased in other quadrants, compared to HC （76.95±14.81μm）. The other quadrants remaining stable for LHON and EON patients besides the second hour sector of pRNFL thickness reduced and the temporal pRNFL decreased （56.78±15.87μm） for EON. Total macular thickness in MON reduced remarkably（279.25±18.90μm; P=0.015）, which mainly occurring in the inner circle （3 mm diameter of circle） and the nasal temporal sectors in the outer circle （5.5 mm diameter of circle）, in contrast to those in HC. RGCL thickness reduced in each sector of the macula （61.90±8.73μm; P≤0.001）. It strongly showed the correlationship of best corrected visual acuity （R=0.50, P=0.0003） and visual field injury （R=0.54,P=0.0002） in MON patients.CONCLUSION：OCT is a potential tool for detecting structural alterations in the optic nerves of various MON. Different types of MON may have different damage patterns.

Stem Cell Ophthalmology Treatment Study (SCOTS)： bone marrow-derived stem cells in the treatment of Leber＇s hereditary optic neuropathy

The Stem Cell Ophthalmology Treatment Study （SCOTS） is currently the largest-scale stem cell ophthal- mology trial registered at ClinicalTrials.gov （identifier： NCT01920867）. SCOTS utilizes autologous bone marrow-derived stem cells （BMSCs） to treat optic nerve and retinal diseases. Treatment approaches include a combination of retrobulbar, subtenon, intravitreal, intra-optic nerve, subretinal, and intravenous injection of autologous BMSCs according to the nature of the disease, the degree of visual loss, and any risk factors related to the treatments. Patients with Leber＇s hereditary optic neuropathy had visual acuity gains on the Early Treatment Diabetic Retinopathy Study （ETDRS） of up to 35 letters and Snellen acuity improvements from hand motion to 20/200 and from counting fingers to 20/100. Visual field improvements were noted. Macular and optic nerve head nerve fiber layer typically thickened. No serious complications were seen. The increases in visual acuity obtained in our study were encouraging and suggest that the use of autolo- gous BMSCs as provided in SCOTS for ophthalmologic mitochondrial diseases including Leber＇s hereditary optic neuropathy may be a viable treatment option.

Optical coherence tomography angiography of optic disc perfusion in non-arteritic anterior ischemic optic neuropathy

AIM：To compare the optic disc blood flow of non-arteritic ischemic optic neuropathy（NAION）eyes with normal eyes.METHODS：The optic disc blood flow densities of diagnosed non-acute phase NAION eyes（21 eyes,14 individuals）and normal eyes（19 eyes,12 individuals）were detected via Optovue optical coherence tomography angiography（OCTA）.The optic disc blood flow was measured via Image J software.Correlations between optic disc perfusion and visual function variables were assessed by linear regression analysis.RESULTS：The average percentage of the optic disc nonperfusion areas in the non-acute phase NAION patients（17.84%±6.18%）was increased,when compared to the normal control eyes（8.61%±1.65%）,and the difference was statistically significant（P〈0.01）.Moreover,there was a proportional correlation between the visual field mean defect（MD）and the optic disc non-perfusion area percentage,and the relationship was statistically significant（t=3.65,P〈0.01,R2=0.4118）.In addition,the critical correlation between the best corrected visual acuity（BCVA）and the optic disc non-perfusion area percentage was statistically significant（t=4.32,P〈0.01,R2=0.4957）.CONCLUSION：The optic disc non-perfusion area percentages detected via OCTA in NAION eyes were significantly increased when compared with the normal eyes.Both the BCVA and MD were correlated with the optic disc flow detected,revealing that OCTA may be valuable in the diagnosis and estimation of NAION.

Prognostic factors of trans-ethmosphenoid optic canal decompression for indirect traumatic optic neuropathy

AIM： To investigate a possible correlation between visual acuity（VA） prognosis and the presence at baseline of various orbital and ocular signs in patients affected by indirect traumatic optic neuropathy（ITON）. METHODS： From July 1 st, 2012 to July 1 st, 2015, 224 adults diagnosed with ITON who underwent endoscopic transethmosphenoid optic canal decompression（ETOCD） were reviewed. Visual outcome before and after treatment were taken into comparison. RESULTS： Accompanied older in age, longer time to medical treatment and existence of optic canal fracture（OCF） were the independent predictors for poor postoperative VA and lower improvement degree of visual acuity（IDVA）, while worse preoperative VA was predictive factor for poor postoperative VA only. Mean value of IDVA in patients with OCF was 0.19±0.30. Mean value of IDVA in patients without OCF was 0.29±0.35. IDVA in cases without OCF was significant higher than those with OCF（t=2.272, P〈0.05）. CONCLUSION： Patients suffered from ITON without OCF before ETOCD have better surgical outcome than those with OCF. Older in age, longer time to medical treatment and existence of OCF are independent factors for poor VA prognosis and lower IDVA. Preoperative VA is independent factor for VA prognosis only.

Indirect traumatic optic neuropathy:modeling optic nerve injury in the context of closed head trauma

Traumatic optic neuropathy:Traumatic brain injury is one of the leading causes of disability and mortality in the United States.It impacts people of all ages and demographics,particularly younger males and members of the military.Vision loss is commonly associated with traumatic brain injuries of all severities and can leave patients permanently disabled.This vision loss can be caused by injury to the visual system at multiple levels,including the eyes,optic nerves,and many different sites in the brain and brainstem(Sen,2017).Despite the far-reaching effects of visual impairment after traumatic brain injury,its incidence after traumatic brain injury is not well measured,and few successful treatments have been identified or implemented.

Newly onset indirect traumatic optic neuropathy-surgical treatment first versus steroid treatment first

AIM: To investigate the efficacy and safety of the treatment of endoscopic trans-ethmosphenoid optic canal decompression(ETOCD) with combination of steroid in patients with newly onset indirect traumatic optic neuropathy(ITON) and compare the outcome between immediate ETOCD treatment and ETOCD with preoperative steroid treatment. METHODS: Patients presented as newly onset ITON(suffered trauma within 3 d) at a tertiary medical center between Mar 1 st, 2016 and Mar 1 st, 2018 were enrolled in this study. All patients were equally and randomly divided into 2 groups. Cases in group A were performed ETOCD immediately after admition while cases in group B were prescribed by methylprednisolone(20 mg/kg · d) for 3 d before ETOCD. Methylprednisolone(20 mg/kg · d) was used after surgery for 6 d in group A and 3 d in group B. Follow-up was up to 3 mo in all cases. Visual acuity(VA) before and after treatment between the two groups were taken into comparison. RESULTS: Complete postoperative data were acquired from 34 patients in group A and from 32 patients in group B. Group A had significantly higher effective rate in VA than group B(χ~2 =4.905, P=0.027).CONCLUSION: For patients with newly onset ITON, combination treatment of ETOCD with high-dose steroid is an effective and safe way. Immediate surgery will lead to better prognosis for these cases.

Stem Cell Ophthalmology Treatment Study(SCOTS) for retinal and optic nerve diseases: a case report of improvement in relapsing auto-immune optic neuropathy

We present the results from a patient with relapsing optic neuropathy treated within the Stem Cell Ophthalmology Treatment Study （SCOTS）. SCOTS is an Institutional Review Board ap- proved clinical trial and has become the largest ophthalmology stem cell study registered at the National Institutes of Health to date （www.clinicaltrials.gov Identifier NCT 01920867）. SCOTS utilizes autologous bone marrow-derived stem cells （BMSCs） for treatment of retinal and optic nerve diseases. Pre-treatment and post-treatment comprehensive eye exams of a 54 year old female patient were performed both at the Florida Study Center, USA and at The Eye Center of Columbus, USA. As a consequence of a relapsing optic neuritis, the patient＇s previously normal visual acuity decreased to between 20/350 and 20/400 in the right eye and to 20/70 in the left eye. Significant visual field loss developed bilaterally. The patient underwent a right eye vitrectomy with injection of BMSCs into the optic nerve of the right eyeand retrobulbar, subtenon and in- travitreal injection of BMSCs in the left eye. At 15 months after SCOTS treatment, the patient＇s visual acuity had improved to 20/150 in the right eye and 20/20 in the left eye. Bilateral visual fields improved markedly. Both macular thickness and fast retinal nerve fiber layer thickness were maximally improved at 3 and 6 months after SCOTS treatment. The patient also reduced her mycophenylate dose from 1,500 mg per day to 500 mg per day and required no steroid pulse therapy during the 15-month follow up.

Mitochondrial variants may influence the phenotypic manifestation of Leber's hereditary optic neuropathy-associated ND4 G11778A mutation

We report here the characterization of a five-generation Han Chinese family with Leber＇s hereditary optic neuropathy （LHON）. Strik- ingly, this Chinese family displayed high penetrance and expressivity of visual loss. The average age-of-onset of vision loss was 18 years in this family. Nineteen （11 males/8 females） of 29 matrilineal relatives in this family developed visual loss with a wide range of severity, ranging from blindness to normal vision. Sequence analysis of mitochondrial genome in this pedigree revealed the presence of the ND4 G 11778A mutation and 44 other variants belonging to Asian haplogroup M7b. The G 11778A mutation is present at homoplasmy in matri- lineal relatives of this Chinese family. Of other variants, the C01 G6480A, ND5 T12811C and Cytb A15395G located at highly conserved residues of corresponding polypeptides. In fact, these variants were implicated to be involved in other clinical abnormalities. Here, these variants may act in synergy with the primary LHON-associated Gl1778A mutation. Thus, the mitochondrial dysfunction caused by the primary ND4 G11778A mutation may be worsened by these mitochondrial variants. The results imply that the G6480A, T12811C and A15395G variants might have a potential modifier role in increasing the penetrance and expressivity of the primary LHON-associated G11778A mutation in this Chinese family.

Protective effects of Rutin against methanol induced acute toxic optic neuropathy：an experimental study

AIM：To determine the effects of Rutin on methanol induced optic neuropathy and compare the results with the effects of ethanol.METHODS：Totally 30 rats were divided into 5 groups,with 6 rats in each group as follows：healthy controls（C）,methotrexate（MTX）,methotrexate＋methanol（MTM）,methotrexate＋methanol＋ethanol（MTME） and methotrexate＋ methanol＋Rutin（MTMR）.In all rabbits except those of the control group,MTX,diluted in sterile serum physiologic,0.3 mg/kg per oral was applied for 7 d by the aid of a tube.After this procedure to the rats of MTM,MTME and MTMR groups,20% methanol with a dose of 3 g/kg per oral was given by the aid of a tube.In MTME group,4 h after the application of methanol,20% ethanol was applied by the same way with a dose of 0.5 g/kg.On the other hand,in MTMR group 4 h after the application of methanol,Rutin,which was dissolved in distilled water,was applied by the same way with a dose of 50 mg/kg.RESULTS：There were statistically significant differences in tissue 8-hydroxy-2 deoxyguanine（8-OHdG）,interleukin-1β（IL-1β）,tumor necrosis factor-alpha（TNF-α）,malondialdehyde（MDA）,myeloperoxidase（MPO）.glutathione peroxidase（t GSH） and superoxide dismutase（SOD） levels between groups（P〈0.001）.In MTMR group tissue 8-OHdG,IL-1β,MDA,and MPO levels were similar with the healthy controls but significantly different than the other groups.In histopathological evaluations,in MTX group there was moderate focal destruction,hemorrhage and decrease innumber of astrocytes and oligodendrocytes;in MTM group there was severe destruction and edema with decrease in number of astrocytes and oligodendrocytes;in MTME group there was mild hemorrhage,mild edema,mildly dilated blood vessels with congestion while in MTMR group,optic nerve tissue was resembling the healthy controls.CONCLUSION：Rutin may prevent methanol-induced optic neuropathy via anti-inflammatory effects and decreasing the oxidative stress.New treatment options are warranted in this disease to avoid loss of vision in patients.