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.

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.

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.

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.

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.

Toxocara optic neuropathy: clinical features and ocular findings

We evaluated thirteen eyes of twelve patients diagnosed clinically and serologically with Toxocara optic neuropathy. Eleven patients had unilateral involvement and one patient had bilateral optic neuropathy. Eight patients （66.7%） had a possible infection source to Toxocara. Six patients （50%） had painless acute optic neuropathy. Ten eyes had asymmetric, sectorial optic disc edema with peripapillary infiltration and three eyes had diffuse optic disc edema. Eosinophilia was noted in five patients （41.7%） and optic nerve enhancement was observed in eight of eleven eyes （72.7%） with available orbit magnetic resonance imaging （MRI）. Mean visual acuity significantly improved following treatment [mean logarithmic of the minimum angle of resolution （IogMAR） 0.94±0.56 at baseline and 0.47±0.59 at the final （P=0.02）]. Asymmetric optic disc edema with a peripapillary lesion and a history of raw meat ingestion were important clues for diagnosing Toxocara optic neuropathy. Additionally, Toxocara IgG enzymelinked immunosorbent assay （ELISA） test and evaluating eosinophil may be helpful for diagnosis.

Clinical characteristics of progressive nonarteritic anterior ischemic optic neuropathy

AIM:To study whether patients with progressive nonarteritic anterior ischemic optic neuropathy(NAION)present earlier than patients with stable NAION and to describe their clinical characteristics and visual outcome.METHODS:This was a retrospective chart review.All patients with NAION seen during the acute stage from January 2012 to December 2018 were reviewed.Patients were included if they had documented disc edema and follow up of at least 3 mo.Patients with progressive NAION were identified if they worsened in 2 out of 3 parameters:visual acuity≥3 Snellen lines;Color vision≥4 Ishihara plates;the visual field defect involved a new quadrant.The clinical characteristics,time from symptom onset to presentation,systemic risk factors and visual outcome were compared to patients with stable NAION.RESULTS:Totally 122 NAION cases met the inclusion criteria.Mean age was 58.1 y(range 22-74),70%were men.Twenty cases(16.4%)had progressive NAION.Patients with progressive NAION did not differ from stable NAION in their demographics,systemic risk factors or in their initial visual deficit.At last follow up,median visual acuity was 1.0 log MAR(IQR 0.64-1.55)in patients with progressive NAION,vs 0.18(IQR 0.1-0.63)in stable NAION(P<0.001).Median color vision testing was 0 plates correct(IQR 0-2.5%)vs 92%plates correct(IQR 50%-100%)in the stable NAION group(P<0.001).Patients with progressive NAION differed in the time from symptom onset to presentation(median 2 d vs 5 d,P=0.011).CONCLUSION:We find no identifiable risk factors associated with progressive NAION.Progressors arrive earlier for ophthalmological evaluation.

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.

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.

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.

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.

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.

Glaucomatous optic neuropathy treatment options:the promise of novel therapeutics,techniques and tools to help preserve vision

Peripheral vision loss followed by ＂tunnel vision＂ and eventual irreversible blindness is the fate of patients afflicted by various forms of glaucoma including primary open-angle glaucoma（POAG） and normotensive glaucoma（NTG）.These complex and heterogeneous diseases are characterized by extensive death of retinal ganglion cells（RGCs） accompanied by retraction and severance of their axonal connections to the brain and thus damage to and thinning of the optic nerve.Since patients suffering from this glaucomatous optic neuropathy（GON） first notice visual impairment when they have lost 〉 40% of their RGCs,early diagnosis is the key to retard the progression of glaucoma.Elevated intraocular pressure（IOP）,low cerebrospinal and/or low intracranial fluid pressure,advancing age,and ethnicity are major risk factors associated with POAG.However,retinal vascular abnormalities and a high sensitivity of RGCs and optic nerve head components to neurotoxic,inflammatory,oxidative and mechanical insults also contribute to vision loss in POAG/GON.Current treatment modalities for POAG and NTG involve lowering IOP using topical ocular drugs,combination drug products,and surgical interventions.Two recently approved multi-pharmacophoric drugs（e.g.,rho kinase inhibitor,Netarsudil;a drug conjugate,Latanoprostene Bunod） and novel aqueous humor drainage devices（i Stent and Cy Pass） are also gaining acceptance for treating POAG/NTG.Neuroprotective and regenerative agents,coupled with electroceutical,mechanical support systems,stem cell transplantation and gene therapy are emerging therapeutics on the horizon to help combat GON.The latter techniques and approaches hope to rejuvenate RGCs and repair the optic nerve structures,thereby providing a gain of function of the visual system for the glaucoma patients.

Change of retinal nerve fiber layer thickness in patients with nonarteritic inflammatory anterior ischemic optic neuropathy

In this study, 16 patients （19 eyes） with nonarteritic anterior ischemic optic neuropathy in the acute stage （within 4 weeks） and resolving stage （after 12 weeks） were diagnosed by a series of complete ophthalmic examinations, including fundus examination, optical coherence tomography and fluorescein fundus angiography, and visual field defects were measured with standard automated perimetry. The contralateral uninvolved eyes were used as controls. The retinal nerve fiber layer thickness was determined by optical coherence tomography which showed that the mean retinal nerve fiber layer thickness and the retinal nerve fiber layer thickness from temporal, superior, nasal and inferior quadrants were significantly higher for all measurements in the acute stage than the corresponding normal values. In comparison, the retinal nerve fiber layer thickness from each optic disc quadrant was found to be significantly lower when measured at the resolving stages, than in the control group. Statistical analysis on the correlation between optic disc nerve fiber layer thickness and visual defects demonstrated a positive correlation in the acute stage and a negative correlation in the resolving stage. Our experimental findings indicate that optical coherence tomography is a useful diagnostic method for nonarteritic anterior ischemic optic neuropathy and can be used to evaluate the effect of treatment.

Efficacy of granulocyte-colony stimulating factor treatment in a rat model of anterior ischemic optic neuropathy

Non-arteritic anterior ischemic optic neuropathy （NA-AION） is the most common cause of acute ischemic damage to the optic nerve （ON）, and the leading cause of seriously impaired vision in people over 55 years of age. It demonstrated that subcutaneous administration of Granulocyte colony-stimulating factor （G-CSF） reduces RGC death in an ON crush model in rats, and that the neuroprotective effects may involve both anti-apoptotic and anti-inflammatory processes. Our recent work shows that the protective actions of G-CSF in rAION models may involve both anti-apoptotic and anti-inflammatory processes. However, the exact rescuing mech- anisms involved in the administration of G-CSF in rAION models need further investigation. In addition, further studies on the administration of G-CSF at different time intervals after the induction of rAION may be able to illustrate whether treatment given at a later time is still neu- roprotective. Further, it is unknown whether treatment using G-CSF combined with other drugs will result in a synergistic effect in a rAION model. Inflammation induced by ischemia plays an essential role on the ON head in NA-A1ON, which can result in disc edema and compartment changes. Therefore, it is reasonable that adding an anti-inflammatory drug may enhance the therapeutic effects of G-CSF. An ongoing goal is to evaluate the novel sites of action of both G-CSF and other anti-inflammatory drugs, and to identify the functionally protective pathways to enhance RGC survival. These investigations may open up new therapeutic avenues for the treatment of ischemic optic neuropathy.

A Meta-analysis of the association between different genotypes(G11778A, T14484C and G3460A ) of Leber hereditary optic neuropathy and visual prognosis

AIM：To analyze the influences of different genotypes（G11778A,T14484 C and G3460A） of Leber hereditary optic neuropathy（LHON） on visual prognosis. METHODS： After a systematic literature search,all relevant studies evaluating the association between the three primary mutations of LHON and visual prognosis were included.All statistical tests were calculated with Revman 5.2 and STATA 12.0. RESULTS： Ten independent studies were included finally.A significant association between the three primary mutations and prognostic vision over 0.3 were found in G11778 A versus T14484 C [odds ratio（OR） =0.10,95% confidence interval（CI） =0.05-0.17,P 〈0.001],G11778 A versus G3460A（OR=0.18,95%CI=0.09-0.37,P 〈0.001） and T14484 C versus G3460A（OR =2.45,95% CI =1.10-5.48,P 〈0.05）.In addition,obtained by pairwise comparison,the vision during onset,age of onset and sex ratio of these three kinds of patients,have no statistical significance（P 〉0.05）.CONCLUSION： From pairwise comparison,we conclude that these three different genotypes of LHON are related to patients＇ visual prognosis.The T14484 C patients might have a best prognostic vision,G3460 A second,and G11778 A worst.And there is little relation between the three different genotypes and patients＇ vision,age of onset and sex ratio.

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.

The transcorneal electrical stimulation as a novel therapeutic strategy against retinal and optic neuropathy: a review of experimental and clinical trials

Transcorneal electrical stimulation （TES） is a novel therapeutic approach to activate the retina and related downstream structures. TES has multiple advantages over traditional treatments, such as being minimally invasive and readily applicable in a routine manner. Series of animal experiments have shown that TES protects the retinal neuron from traumatic or genetic induced degeneration. These laboratory evidences support its utilization in ophthalmological therapies against various retinal and optical diseases including retinitis pigmentosa （RP）, traumatic optic neuropathy, anterior ischemic optic neuropathy （AION）, and retinal artery occlusions （RAOs）. Several pioneering explorations sought to clarify the functional mechanism underlying the neuroprotective effects of TES. It seems that the neuroprotective effects should not be attributed to a solitary pathway, on the contrary, multiple mechanisms might contribute collectively to maintain cellular homeostasis and promote cell survival in the retina. More precise evaluations y/a functional and morphological techniques would determine the exact mechanism underlying the remarkable neuroprotective effect of TES. Further studies to determine the optimal parameters and the long-term stability of TES are crucial to justify the clinical significance and to establish TES as a popularized therapeutic modality against retinal and optic neuropathy.

Establishing an experimental model of photodynamic induced anterior ischemic optic neuropathy

BACKGROUND： Scholars have supposed to establish animal models of optic neuropathy by pressing and partially amputating optic nerve, increasing intraocular pressure and injecting vasoconstrictor, etc., but the models are greatly different from anterior ischemia optic neuropathy. Therefore, a more ideal method is needed to establish animal model of anterior ischemic optic neuropathy （AION）. OBJECTIVE ： To establish AION models in rats, observe the functional changes of fundus, fundus fluorescein angiography （FFA）, optical coherence tomography （OCT）, flash visual evoked potential （F-VEP）, and histopathologically confirm its reliability. DESIGN： A randomized control tria SETTINGS ： Department of Ophthalmology, Xi＇an Fourth Hospital; Xi＇an Institute of Ocular Fundus Diseases MATERIALS ： The experiments were carried out in the research room of Xi＇an Institute of Ocular Fundus Diseases from February 2005 to May 2006. Thirty healthy male SD rats of 4-5 weeks old, weighing 140-160 g, were provided by the animal experimental center of the Fourth Military Medical University of Chinese PLA [SCXK （Military）2002-005], and those without eye disease examined by slit lamp and direct ophthalmoscope after mydriasis were enrolled. The conditions for feeding mice without special pathogen were strictly followed. The rats were randomly divided into blank control group （n =5）, laser group （n =5）, hematoporphyrin derivative （HPD） group and AION group （n =15）, each group was numbered randomly. For each rat, the right eye was taken as the experimental eye, and the left one as the control one. METHODS： In the AION group, the rats were injected with HPD （10 mg/kg） via caudal vein, and then the optic discs were exposed to krypton red （647 nm, 80 mV） for 120 s, and the rats were in avoidance of light for 2 weeks postoperatively. Rats in the laser group were only exposed to krypton red （647 rim, 80 mV） for 120 s, and in avoidance of light for 2 weeks postoperatively; Those in the HPD group were only injected with HPD （10 mg/kg） via caudal vein; Those in the blank control group were untouched. （1） Visual electrophysiological test： The F-VEP was used to evaluate the function of visual nerve. （2） FFA： After mydriasis and anesthesia as describe above, the fluorescein sodium parenteral solution （1 mL/kg） was injected v/a caudal vein and finished within about 3 s, the time of FFA was recorded from the beginning of injection, the video sight aimed at the optic disc and the surrounding area. （3） After mydriasis and anesthesia as describe above, the rats were examined with OCT. （4） Histological observation： After hematoxylin and eosin （HE） staining, the optic disc and surrounding blood vessels of retina were observed under light microscope at high power field. MAIN OUTCOME MEASURES： The results of fundus, FFA, visual electrophysiological test and OCT detection within 90 days after model establishment were observed. RESULTS： Of the 30 rats, 1 died after anesthesia in the laser group and 2 died in the AION group respectively, and finally 27 rats were involved in the analysis of results. （1） Changes in fundus： In the AION group, there was edema in upper optic disc and unclear boundary at 1 day after establishment, edema still could be observed at 6 days, and upper optic disc atrophied and appeared as pale at 90 days. （2） FFA results： In the AION group, early ＂low fluorescence＂, middle and late ＂high fluorescence＂ were observed in upper optic disc 1 day after model establishment, and there was ＂low fluorescence＂ at 6 days, and the low fluorescence could be observed all the time at 23 days. （3） Visual electrophysiological changes： In the AION group as compared with the control eyes, the experimental ones had prolonged F-VEP P100 latency [（71.65±8.81）, （57.58±8.38） ms, t =3.148, P =0.012], and decreased wave amplitude [（4.77±1.90）, （10.06±3.66） μV, t =4.082, P =0.003], and these changes lasted to 35 days after model establishment. （4） OCT results： In the AION group, the reflection surface of part nerve fiber layer was higher than the retina plane, the surface was rough and the thickness was increased at 6 days after model establishment. （5） Histopathological results： At 1 day after model establishment, part optic discs had highly edema, edema of nerve fibers, and loose tissue, also accompanied by the displacement of surrounding retina; At 23 days, the optic disc and surrounding nerve fiber layers became thinner, and the numbers of ganglion nuclei in the retina tissue sections were obviously decreased. These changes were not observed in the laser group, HPD group and blank control group. CONCLUSION ： The changes of fundus, FFA, OCT, visual electrophysiology and histopathology confirmed that the krypton red laser irradiation （647 nm） at 2 hours after HPD was injected via caudal vein can establish more ideal animal models of AION.