[Pathogenetic basis of optic nerve atrophy in methanol poisoning]. / Patogeneticheskie osnovy razvitiya atrofii zritel'nogo nerva pri toksicheskom porazhenii metanolom.

Optic nerve atrophy is a pathomorphological consequence of diseases of the peripheral neuron of the visual pathway, manifested as atrophy of nerve fibers of varying severity. The toxic effect of methanol is mainly associated with formic acid and formaldehyde, which suppress the cytochrome system, inhibit oxidative phosphorylation, and thereby cause a deficiency of adenosine triphosphoric acid, to which brain and retinal tissues are especially susceptible. When formiate accumulates, tissue respiration is disrupted, leading to pronounced tissue hypoxia. As a result of such methanol metabolism, metabolic acidosis occurs. Tissue hypoxia develops in the first few hours as a result of the action of formic acid on the respiratory enzyme chain at the cytochrome oxidase level. Hypoxia and, as a consequence, a decrease in energy supply lead to a disruption of biological oxidation and the development of apoptosis in the optic nerve fibers. Understanding the process of optic nerve atrophy development at the pathogenetic level in methyl alcohol intoxication will help make a correct early diagnosis and prescribe timely treatment.

Potentially blinding adverse drug reaction to peribulbar lignocaine anesthesia: A rare case report.

Peribulbar lignocaine anesthesia is commonly used in ophthalmic surgeries. It rarely causes any severe allergic reaction. A 63-year-old male presented with complicated pseudophakia. He underwent successful vitrectomy under local anesthesia. He later presented with acute-onset proptosis, orbital swelling, and extraocular movement restriction. He was afebrile with normal blood workup and radiological investigations and gave a similar past history. The patient was treated successfully with intravenous medications but two months later developed optic atrophy. An adverse reaction to lignocaine appears to be the most probable cause. Early detection and prompt management of this condition may avert a potentially grave visual outcome. Literature review shows that this case is one of its kinds to report this potentially blinding complication of peribulbar lignocaine anesthesia.

Optic atrophy after cabazitaxel treatment in a patient with castration-resistant prostate cancer: a case report.

Taxanes are a group of cytotoxic anti-cancer agents used in the treatment of solid tumours. The neurotoxic adverse effects of docetaxel and paclitaxel, including optic neuropathy, are well known. Cabazitaxel is a new generation taxane showing lesser drug resistance when compared with previous ones. Optic atrophy due to the use of cabazitaxel has not been previously reported. Herein, we report a patient with prostate cancer who developed optic atrophy after cabazitaxel treatment.

NEGATIVE EFFECTS OF VITAL DYES AFTER UNEVENTFUL VITREOMACULAR SURGERY.

PURPOSE: Vital dyes have become a clinical standard during chromovitrectomy but toxicity remains an issue. We compared the clinical outcome of one supposedly toxic vital dye (AV 17 with 5% mannitol) with a standard vital dye (MBB Dual) and performed a power analysis for future comparative studies. METHODS: Retrospective analysis of 270 eyes after chromovitrectomy with internal limiting membrane peeling because of macular holes. Primary endpoint was loss in BCVA >2 lines and photoreceptor atrophy as seen on optical coherence tomography examination. RESULTS: In 173 eyes, staining of the epiretinal membrane and extracellular matrix was performed using MBB (Group A), and in 97 using AV 17-M (Group B). The mean BCVA was not significantly different after more than 3 months and also not in the early postoperative period after surgery between Group A and Group B. The number of patients suffering from a decline in BCVA of two lines and more was not significantly higher in patients of Group B. There was not a significantly higher percentage of patients with an inner segment/outer segment defect. CONCLUSION: Our rather homogeneous study showed no significant difference between both dyes. Thousand five hundred patients would need to be examined to find a significant difference in future studies.

Visual and neurologic sequelae of methanol poisoning in Saudi Arabia.

OBJECTIVES: To present the visual sequelae of methanol poisoning and to emphasize the characteristics of methanol exposure in the Kingdom of Saudi Arabia (KSA). METHODS: A retrospective case series was carried out on 50 sequential patients with methanol poisoning seen at the King Khaled Eye Specialist Hospital and King Saud University Hospitals in Riyadh, KSA between 2008 and 2014. All patients were examined by a neuro-ophthalmologist at least one month after methanol intoxication. RESULTS: All 50 patients were young or middle-aged males. All admitted to drinking unbranded alcohol within 2-3 days before profound or relatively profound, painless, bilateral visual loss. Mean visual acuity in this group was hand motions (logMAR 2.82; range 0.1 - 5.0) with some eye to eye variability within individuals. Worse visual acuity was correlated with advancing age (Pearson correlation: oculus dextrus [right eye] - 0.37, p=0.008; oculus sinister [left eye] - 0.36, p=0.011). All patients had optic atrophy bilaterally, and all tested patients had visual field defects. Tremors with or without rigidity were present in 12 patients, and 11 of 30 patients who had neuroimaging performed had evidence of putaminal necrosis. CONCLUSION: Methanol intoxication causes visual loss within 12-48 hours due to relatively severe, painless, bilateral optic nerve damage that may be somewhat variable between eyes, and is generally worse with advancing age. The coincidence of bilateral optic nerve damage and bilateral putaminal necrosis in a young or middle-aged male is very suspicious for methanol-induced damage.

ENU mutagenesis identifies mice modeling Warburg Micro Syndrome with sensory axon degeneration caused by a deletion in Rab18.

Mutations in the gene of RAB18, a member of Ras superfamily of small G-proteins, cause Warburg Micro Syndrome (WARBM) which is characterized by defective neurodevelopmental and ophthalmological phenotypes. Despite loss of Rab18 had been reported to induce disruption of the endoplasmic reticulum structure and neuronal cytoskeleton organization, parts of the pathogenic mechanism caused by RAB18 mutation remain unclear. From the N-ethyl-N-nitrosourea (ENU)-induced mutagenesis library, we identified a mouse line whose Rab18 was knocked out. This Rab18(-/-) mouse exhibited stomping gait, smaller testis and eyes, mimicking several features of WARBM. Rab18(-/-) mice were obviously less sensitive to pain and touch than WT mice. Histological examinations on Rab18(-/-) mice revealed progressive axonal degeneration in the optic nerves, dorsal column of the spinal cord and sensory roots of the spinal nerves while the motor roots were spared. All the behavioral and pathological changes that resulted from abnormalities in the sensory axons were prevented by introducing an extra copy of Rab18 transgene in Rab18(-/-) mice. Our results reveal that sensory axonal degeneration is the primary cause of stomping gait and progressive weakness of the hind limbs in Rab18(-/-) mice, and optic nerve degeneration should be the major pathology of progressive optic atrophy in children with WARBM. Our results indicate that the sensory nervous system is more vulnerable to Rab18 deficiency and WARBM is not only a neurodevelopmental but also neurodegenerative disease.

Hemorrhagic retinal infarction due to inadvertent overdose of cefuroxime in cases of complicated cataract surgery: retrospective case series.

PURPOSE: To present 4 patients that developed hemorrhagic retinal infarction attributable to inadvertent overdose of cefuroxime after cataract surgery. DESIGN: Case series. SUBJECTS AND METHODS: Surgery in 4 patients was complicated-the posterior capsule was absent or torn-and anterior vitrectomy was performed. Cefuroxime was inadvertently injected at a dose higher than recommended in all 4 cases. RESULTS: Case 1 had hemorrhage in the central and inferior retinal regions, as well as optic atrophy. Case 2 had hemorrhage in the peripapillary and macular regions, as well as optic atrophy. Case 3 had hemorrhage in the peripapillary and inferior retinal regions, as well as macular pucker attributable to fibrovascular formation in the central retinal region. Case 4 had hemorrhage in the peripapillary, macular, and inferior retinal regions. The cefuroxime doses administered to the presented patients were much higher than reported in other cases and resulted in a higher concentration in the vitreous. Consequently, the severity of toxicity was much higher than in other reported cases of cefuroxime-induced toxicity. CONCLUSION: In cases of intracameral cefuroxime overdose, hemorrhagic retinal infarction can develop after cataract surgery.

Bilateral total optic atrophy due to transdermal methanol intoxication.

In this case report, we document a 54-year-old woman with total bilateral optic nerve atrophy after local application of methanol containing spirit. Almost all the reported cases of methanol intoxication in the literature are caused by oral ingestion. In this rare case, we present transdermal absorption of methanol that may cause irreversible blindness in addition to intracerebral lesions.

Optic atrophy after anti-vascular endothelial growth factor injection in diabetic patients with proliferative diabetic retinopathy.

OBJECTIVE: To study the prevalence of optic atrophy in patients with proliferative diabetic retinopathy (PDR) who underwent intravitreal bevacizumab injection and risk factors associated with optic atrophy. MATERIAL AND METHOD: A retrospective case control study enrolled 269 cases (394 eyes) of patients with PDR, in which 166 cases (219 eyes) received intravitreal bevacizumab injection. Associated factors such as type of DM, hemoglobin A1c level, hypertension, hypercholesterolemia, chronic kidney disease, previous intravitreal surgery retinal detachment, and vitreous hemorrhage were recorded. Criteria for diagnosis of optic atrophy were decreased visual acuity, pale optic disc and decreased nerve fiber layer thickness, which was measured by Stratus optical coherence tomography (OCT). The association between intravitreal bevacizumab injection and optic atrophy was analyzed by multiple logistic regression. RESULTS: Two hundred sixty nine patients with PDR, consisting of 166 patients with intravitreal bevacizumab injection and 103 cases without bevacizumab injection. Optic atrophy was found in 11.4% (25/219 eyes) and 8% (14/175 eyes) respectively. There was no evidence that intravitreal bevacizumab injection and associated systemic diseases were related to optic atrophy. The risk factor that was related to optic atrophy was previous intravitreal surgery (adjusted odds ratio (OR), 2.57 [95% CI, 1.13, 5.84], p = 0.024). CONCLUSION: Anti-VEGF (bevacizumab) does not increase the risk of optic atrophy. The ophthalmologists should be aware of subsequent optic atrophy development in patients with PDR who undergo surgical intervention.

Are phosphodiesterase type 5 inhibitors associated with vision-threatening adverse events? A critical analysis and review of the literature.

INTRODUCTION: Phosphodiesterase type 5 (PDE5) inhibitors are the first line drugs for treatment of erectile dysfunction. Sildenafil (Viagra(R)), tadalafil (Cialis(R)), and vardenafil (Levitra(R)) are from the same class of drugs that inhibit PDE5. Transient visual symptoms such as change in color perception and increased light sensitivity are well-known adverse effects of these drugs and occur in 3-11% of sildenafil users. Vision-threatening (serious) ocular complications, such as nonarteritic ischemic optic neuropathy and cilio-retinal artery occlusion have rarely been reported in PDE5 inhibitor users. AIMS: To highlight and analyze the most recently published case literature on serious ocular complications of PDE5 inhibitors. METHODS: Search of the peer-reviewed English literature was conducted using Medline. The following databases also were searched: Cumulative Index to Nursing and Allied Health Literature, Cochrane Library, Global Health, and MD Consult. The causality assessment of the reported adverse drug reactions was analyzed by applying both the World Health Organization (WHO) Probability Scale and the criteria utilized by the National Registry of Drug-Induced Ocular Side Effects. MAIN OUTCOME MEASURES: To scientifically and objectively find out if PDE5 inhibitors are associated with vision-threatening ocular complications. RESULTS: Eight case reports of serious PDE5 inhibitor-associated ocular complications were identified since January 2006 until February 2011. Case reports included cases of anterior and posterior nonarteritic ischemic optic neuropathy, central retinal vein occlusion, cilio-retinal artery occlusion, acute angle closure glaucoma and optic atrophy after sildenafil use. CONCLUSION: There is lack of conclusive evidence to indicate a direct cause-effect relationship between PDE5 inhibitor use and vision-threatening ocular events. Men who use PDE5 inhibitors appear to suffer vision-threatening complications at the same frequency as the general population. However, minor visual adverse effects occur in 3-11% of users and they are transient and reversible.

A case of optic nerve atrophy with severe disc cupping after methanol poisoning.

We report a rare case of optic nerve atrophy with severe disc cupping resulting from methanol poisoning. A 30-year-old man presented to the hospital complaining of decreased visual acuity in both eyes a day after drinking alcohol containing methanol. His initial visual acuity allowed for only visualizing hand motion and not corrected in either eye. Initial intraocular pressure was within normal limits in both eyes. Initial fundus examination showed optic disc swelling in both eyes. Four years later, he visited our hospital for an eye evaluation. Visual acuity in both eyes still only allowed for visualizing hand motion. No nystagmus was observed in either eye during the optokinetic nystagmus test, and no waves were found in a visual evoked potential test. No specific change was noted on brain magnetic resonance imaging. On fundus examination, there was disc pallor in both eyes and disc cupping with a high cup/disc (C/D) ratio above 0.9 in the left eye. C/D ratio of the right eye was 0.5. Methanol poisoning may induce glaucomatous disc cupping in the late stage as well as optic atrophy. One possible mechanism of disc cupping is ganglion cell loss due to acute demyelination of the retrobulbar optic nerve. This report is the first photographic evidence of methanol induced optic disc cupping in Korea.

Taurine deficiency damages photoreceptors and retinal ganglion cells in vigabatrin-treated neonatal rats.

The anti-epileptic drug vigabatrin induces an irreversible constriction of the visual field, but is still widely used to treat infantile spasms and some forms of epilepsy. We recently reported that vigabatrin-induced cone damage is due to a taurine deficiency. However, optic atrophy and thus retinal ganglion cell degeneration was also reported in children treated for infantile spasms. We here show in neonatal rats treated from postnatal days 4 to 29 that the vigabatrin treatment triggers not only cone photoreceptor damage, disorganisation of the photoreceptor layer and gliosis but also retinal ganglion cell loss. Furthermore, we demonstrate in these neonatal rats that taurine supplementation partially prevents these retinal lesions and in particular the retinal ganglion cell loss. These results provide the first evidence of retinal ganglion cell neuroprotection by taurine. They further confirm that taurine supplementation should be administered with the vigabatrin treatment for infantile spasms or epilepsy.

Anterior segment ischemia and retinochoroidal vascular occlusion after intralesional steroid injection.

A 19-year-old woman was admitted with sudden severe pain and loss of light perception that began immediately after eyelid injection of the depot form of corticosteroid. Ecchymosis of the lower eyelid, corneal edema, and a fixed dilated pupil were noted. Fundus examination could not be performed because of corneal edema. Embolic material packed in the episcleral vessels was detected. With these findings, the diagnosis was anterior and posterior segment ischemia. Despite administration of an intravenous hyperosmotic agent, in addition to topical and systemic pulse corticosteroid (1.0 g/day), vision was not recovered. The most serious complication of intralesional injection of corticosteroid is vascular occlusion. This catastrophic complication after intralesional steroid injection should prompt immediate ophthalmoscopic fundus examination to allow early recognition of ischemic signs and immediate intervention.