It starts from eyeball to optic foramen. It is covered by dura, arachnoid, pia. The pial sheath contains capillaries and sends septae to divide the nerve into fasciculi. The subarachnoid space contains cerebrospinal fluid. The central retinal artery along with its vein crosses the subarachnoid space to enter the nerve on its inferomedial part. Anteriorly nerve is separated from extraocular muscles by the orbital fat. Posteriorly optic nerve is surrounded by annulus of Zinn and orgin of four rectus muscles. Some fibres of superior rectus muscle and medial rectus muscle are adhered to optic nerve sheath and accounts for pain on ocular movements seen in retrobulbar neuritis. The long and short ciliary nerves and arteries surround the optic nerve before these enter the eyeball.
Opticneuritis (ON) is a common presenting symptom in pediatric CNS demyelinating disorders and may be associated with dramatic visual loss. Knowledge regarding clinical presentation, associated diseases, therapy, and outcomes in ON in children has grown over the past decade. These studies have shown that younger children (,10 years of age) are more likely to present with bilateral ON and older children with unilateral ON. Furthermore, studies focusing on visual recovery have shown excellent recovery of high-contrast visual acuity in the majority of children, but functional and structural studies have shown evidence of irreversible injury and functional decline after ON in children. Although randomized controlled treatment trials have not been performed in children and adolescents with ON, standard of care suggests that the use of high- dose pulse steroids is safe and likely effective. This article reviews current knowledge about the clinical presentation and management of pediatric ON, with attention to associated syndromes and evaluative tools that may inform diagnosis and interventions. Neurology ® 2016;87 (Suppl 2):
Our patients with SLE experienced recurrent severe unilateral or bilateral ON with loss of visual acuity worse than 20/400. Mean number of ON attacks was highest in the vasculitis group. Additional neurological and systemic symptoms and signs were observed during follow-up. Laboratory tests as well as brain and spinal cord MRI aided final diagnosis. Response to corticoste- roid therapy was limited, and aggressive immunosuppressive treatment was required to control the disease process.
further studies are needed for verification. Second, VEP amplitude will be affected by other causes of visual acuity loss because the pattern reversal visual evoked response (PVER) mainly represents the function of the macula and optic nerve [20-22]. However, we tried to exclude patients with disability registry with retinal dis- ease by reviewing the results of multifocal ERG and FAG. Third, there has been controversy about the relationship between amplitude of VER and age [23,24]. The unilateral amblyopia group in our study consisted of patients requiring exam for entering the army. There- fore, they were all about 20 years of age. We should consider age differences affecting VEP in future studies. Fourth, the statistical result of opticneuritis in the differ- ence between actually measured visual acuity and func- tion value was marginal (p = 0.07). This non-significant
Chapter 2 explored the effects of SIRT1 or NRF2 gene transfer in experimental opticneuritis. Under cellular conditions of redox equilibrium, NRF2 is sequestered within the cytoplasm and subject to proteasomal-mediated degradation (Dinkova-Kastova et al., 2002; Itoh et al., 2003; McMahon et al., 2003). During oxidative challenge, modifications to critical binding proteins free NRF2 to translocate into the nucleus, recruit transcriptional machinery to antioxidant response elements (AREs), and stimulate transcription of target genes associated with antioxidant defense and cellular detoxification (Johnson et al., 2015). SIRT1 is recruited to the nucleus and other cellular compartments where it modulates the activity of various protein targets. SIRT1 is known to deacetylate and inhibit the transcription factor, p53, thereby downregulating apoptotic gene expression and thus improving cell viability (Luo et al., 2001). SIRT1 promotes mitochondrial function and antioxidant metabolism by activating PGC-1α, a master transcriptional regulator of these responses (Nemoto et al., 2005). While SIRT1 and NRF2 are typically believed to function via separate pathways, recent evidence suggests SIRT1 involvement in regulating the expression and activation of NRF2 (Ding et al., 2016). In addition, treatment with pharmacological agents such as resveratrol, a known activator of SIRT1, was shown to enhance NRF2 expression and activity of its downstream effectors (Zhang et al., 2016; Xia et al., 2017). We hypothesized that gene augmentation of NRF2 or SIRT1 within RGCs could ameliorate pathological features of experimental opticneuritis. Our data demonstrates distinct effects upon RGC survival and functionfollowing AAV2-mediated overexpression of NRF2 or SIRT1, suggesting these candidate factors promote neuroprotective mechanisms that may modify MS pathogenesis.
In most cases, visual functions return to near normal within eight to ten weeks, but they may also advance to a complete and permanent state of visual loss. Therefore, systemic intravenous treatment with corticosteroids, which may quicken the healing of the optic nerve, is often recommended, but it does not have a significant effect on the visual acuity at one year, when compared against placebo. Intravenous corticosteroids have also been found to reduce the risk of developing MS in the following two years in those patients who have MRI lesions; but this effect disappears by the third year of follow up 26 .
In trials of disease-modifying MS medications that have included visual outcomes, treatment benefit on visual func- tion has been demonstrated. There are candidates in the pipeline and on the market to improve visual outcomes following acute opticneuritis and to improve optic nerve function in patients with established optic neuropathy. Two recently approved disease-modifying MS drugs have specific neuro-ophthalmic risks. Fingolimod is associated with a low risk of ME that responds well to treatment dis- continuation. Alemtuzumab is associated with autoimmune thyroid dysfunction and thyroid orbitopathy in a proportion of those affected. Many of the newer disease-modifying MS drugs have powerful immune effects and are associated with potentially life-threatening infections including PML and herpes virus infections. However, absence of evidence is not evidence of absence with regard to both benefit and harm. Clinical experience in terms of numbers of patients treated and longer durations of treatment are necessary to determine the incidence and extent of many harmful consequences.
Corticosteroids (CS) have been recommended for treating acute ON relapses. There is still no consensus about the application of CS (intravenous [iv] or oral forms), dosage, and treatment duration. Often, clinical presentation of opticneuritis is the main factor for the decision maker for initiat- ing and duration of acute therapy. ONTT is a multicentered randomized clinical trial that assessed multiple parameters for patients with ON. ONTT also questioned acute management strategies and in a previous study, patients were assigned to three groups: 1) patients on oral prednisone (1 mg/kg/d for 14 days), 2) patients who received iv methylprednisolone (MP, 250 mg every 6 hours for 3 days) followed by an oral prednisone taper (1 mg/kg/d for 11 days), or 3) patients on oral placebo (for 14 days). Each regimen was followed by a short oral dosage taper of prednisone or placebo on days 15, 16, and 18. ONTT showed that while high-dose CS accelerated visual recovery, long-term visual outcome did not change when compared to the placebo. Visual outcomes for the patient group on oral CS did not improve and ONTT results even showed an increased recurrence rate in the same or fellow eye (twofold). Thus, the recommendation of ONTT is to treat acute ON with iv high-dose CS. Oral CS treat- ments did not seem to have a beneficial effect and thus they are not recommended. 30,31 When patients were followed up
and were not considered typical of MS, and hypothalamic involvement has been emphasized . NMO has a more negative outcome than MS, with frequent and early relapses. Within 5 years of onset, 50% of patients have become blind in both eyes and cannot walk unassisted, and 20% die of respiratory failure due to cervical myelitis . Although no controlled therapeutic trials have been specifically performed in NMO, case series and observa- tional studies suggest that azathioprine in combination with oral steroid reduces the frequency of attacks [4,5], and rituximab and plasmapheresis can induce clinical remission of NMO [6-8]. Immuno-suppression rather than interferon β is the preferred treatment. Thus, distin- guishing NMO from MS is very important for the thera- peutic strategy of these disorders. Recently, clinical,
Abstract: The involvement of macular function in its preganglionic elements, during the neurodegenerative process of multiple sclerosis (MS), is controversial. In this case-control observational and retrospective study, we assessed multifocal electroretinogram (mfERG) responses from 41 healthy Controls, 41 relapsing-remitting MS patients without opticneuritis (ON) (MS-noON Group), 47 MS patients with ON: 27 with full recovery of high-contrast best corrected visual acuity (BCVA) (MS-ON-G Group) and 20 with poor recovery of BCVA (MS-ON-P Group). MfERG N1 and P1 implicit times (ITs), and N1-P1 response amplitude densities (RADs) were measured from concentric rings (R) with increasing foveal eccentricity: 0-5° (R1), 5-10° (R2), 10-15° (R3), 15-20° (R4), 20- 25° (R5), and from retinal sectors [superior, nasal, inferior and temporal] between 0-15° and 0- 25°. In MS-ON-P Group, mean mfERG RADs detected from R1 (0-5°) and from the central nasal quadrant (0-15°) were significantly reduced (p<0.01) with respect to those of Control, MS-noON and MS-ON-G Groups. No other significant differences between Groups for any mfERG parameters were found. Our results suggest that in MS, exclusively after ON with poor recovery of BCVA, the neurodegenerative process can induce dysfunctional mechanisms involving photoreceptors and bipolar cells of the fovea and of the more central nasal macular area.
All our patients in this study were treated with intra venous methyl prednisolone 250mg four times daily for three days followed by oral prednisolone 1mg per kg body wt for 11 days (As per ONTT guidelines). Majority of patients showed good gain (better than 6/18)in visual acuity after treatment. 11 patients showed visual acuity worse than 6/18 in Snellen chart. Visual acuity was very poor (after treatment) in only 2 patients. We found that poor gain in visual acuity after treatment was due to optic atrophy, lens changes and marked RNFL thinning. Wang Jc et al 41 in 2001 found that 83.9%had 6/12 or better with tratement and 38.7% had 6/6 vision after treatment.
A year and a half later, the patient came to our attention complaining of loss of vision in the right eye, accompanied by headache, neck stiffness, slight subjective left hearing loss and tinnitus. At fundu- scopic examination, optic nerve head edema was de- tected in the right eye (Fig. 3). The relapsing nature of the condition along with the protean clinical mani- festations of the disease through the years raised the suspect of VKH disease. The medical history of the patient was hence retrospectively investigated and the CSF pleocytosis identified at the first presentation was finally correctly reinterpreted. In addition to those de- scribed, the patient reported other preceding episodes of visual loss diagnosed elsewhere as ONs and treated with intravenous steroid therapy followed by slow oral taper. There was no laboratory evidence suggestive of other autoimmune or infective ocular disease entities, nor a previous history of penetrating ocular trauma or surgery. According to revised diagnostic criteria for VKH disease (Read et al., 2001), a diagnosis of in- complete VKH was finally made. She was treated with oral steroid therapy, with partial edema resolution on a 3-months eye examination. A long-term treatment with Azathioprine was then started.
Many of the initial features of A-ON are the same as T-ON but painless or very painful onset is more common (absence of pain was only seen in 8% of people with T-ON in the pivotal OpticNeuritisTreatment Trial ). Severe visual loss with haemorrhages and exudates on fundoscopy are red flags for A-ON, especially in non-Caucasian patients, in whom alternative inflammatory disorders such as sarcoidosis and lupus erythematosis (SLE) have a higher prevalence. Progression of visual loss beyond three weeks of onset, or failure of significant recovery at six weeks, suggest A-ON. The clinical features that help identify patients with A-ON are summarised in Table 1, together with some of the more common alternative causes to consider. Atypical inflammatory causes include neuromyelitis optica spectrum disorder with anti-aquaporin-4 (AQ4) or anti-myelin oligodendrocyte glycoprotein (MOG) antibodies, sarcoidosis, SLE, Behcet s disease or Wegener s granulomatosis and are important to identify
Identifying NMO as soon as possible and putting in place the most adapted treatment is critical for a lesion with poor ocular prognosis and for which vital prognosis is very unfavorable. The VF lesions observed after one episode of ON in NMO are different from those usually observed in MS. Given a total VF loss, the positive predictive value in favor of an NMO was 92.8% and the negative predictive value was 47.3%. Obtained with an ambispective study, these values should be confirmed with a prospective study. The VF analysis helps to invoke the NMO diagnosis when faced with severe or altitudinal lesions that appeared during the first ON attack.
73.3% of the patients (30 eyes) have visual acuity 6/60 or worse during presentation. This included 70.0% (20 eyes) who suffered attacks of papillitis, and 83.4% (10 eyes) with signs of retrobulbar ON. All adult patients were treated with intravenous methylprednisolone and oral corticosteroid as recommended by the OpticNeuritisTreatment Trial 2 , while
In August 1994, after returning from a summer vacation at Cape Cod, Massachusetts, a 16-year-old boy developed a painful, swollen knee (Table 1). He had no recollection of a tick bite during the summer, nor did he remember a skin rash or flu-like illness. A Lyme antibody test was positive. He was treated with tetracycline, 1 g once a day for 10 days, and doxycycline, 100 mg twice a day for 20 days. The arthritis resolved during the course of treatment. Six months later he awoke with blurred vision in his left eye. He had no other symptoms. Ophthalmologic evaluation of the right eye was normal, but examination of the left eye revealed a central scotoma, a swollen optic disk, and a visual acuity of 20/200. He was diagnosed with unilateral anterior opticneuritis. A MRI of the brain was normal, as was spinal fluid analysis, including a negative test for myelin basic protein and negative cultures for syphilis, tuberculosis, and other common bacteria. An antibody test for Lyme disease showed an IgG response of 1600 U by ELISA with 8 bands on Western blot (Table 1). He was treated with a 30-day course of intravenous ceftriaxone, 2 g daily. By the time the antibiotic course was completed, the opticneuritis had completely resolved and vision had improved to 20/30. Four months later his vision had normalized to 20/20. In the subse- quent 6 years he has been well, with no recurrence of visual symptoms or arthritis.
edema resolved and was followed by severe optic atrophy. Neurologic examination, brain and orbits computerized tom- ography and magnetic resonance imaging (MRI) scans, cere- brospinal fluid (CSF) analysis and extensive laboratory investigation including anti-aquaporin 4 antibody assay were unrevealing, except for a weakly positive antinuclear anti- body test (1/160, granular pattern). Because of sequential in- volvement and the lack of significant improvement the patient was considered to have atypical ON, presumably from NMO-spectrum disease. Oral azathioprine 150 mg/day was introduced and kept for the following years. Her visualfunction remained stable, and significant peripapillary RNFL loss developed on sequential spectral-domain (SD) OCT ex- aminations, directed at quantifying peripapillary RNFL. However, high-resolution OCT scanning passing through the optic nerve were not obtained.
In this study, approximately a quarter of participants believed that treatment with corticosteroids improved their final visual outcome. This is in conflict with the ONTT findings presented which clearly emphasized that corticosteroids accelerate visual recovery but do not reduce long term recurrence. There is a significant step between information provided by the clinician and that interpreted by the patients. The information and patient education should not be offered solely on the basis of what professionals believe to be necessary for the patient to know, but also on the basis of what patients want to know. The patients ’ actual worries and uncertainties should be taken as a basis for providing information and answers. In opticneuritis, re-gaining vision is a genuine concern for the patient affected and hence may affect the person ’ s adaptation of what they ’ d like to believe. In promoting patient self care management, the health care professional has an explicit educational role, as well as a monitoring role  to ensure not just information is provided, but that information is correctly interpreted.
Opticneuritis (ON) is defined as inflammation of the optic nerve. This general definition describes a common pathological phenotype, which may be caused by a wide range of heterogeneous conditions, varying greatly in their clinical features, natural history, treatment, and prognosis. The most commonly encountered syndrome is acute, inflam- matory, demyelinating ON that may be associated with multiple sclerosis (MS). This will be referred to as typical ON in this review. Patients with typical ON generally make a good visual recovery and, although steroids are sometimes used to reduce the duration of the clinical attack, the overall visual recovery is unaffected by treatment. This is in contrast to some of the other, atypical, inflammatory, and infective causes of ON, in which the visual prognosis may be poor if left untreated. These types of ON differ in their clinical features from typical ON, and will be referred to collectively as atypical ON in this review. Atypical ON may be associated with non-MS inflamma- tory diseases of the central nervous system (CNS). In these patients, visual recovery is dependent on prompt immunosuppressive treatment, and delays in diagnosis can have serious consequences. Therefore, it is critical that these steroid-responsive, atypical optic neuritides are distinguished from typical ON, in order to select the group of patients who will benefit from immunosuppression.
In the visual system, Jacobson et al. (1979) studied the recovery of visualfunction in cats with experimentally induced degenerative lesions in the intracranial optic nerve. Visualfunction was quantified by the ability to recognize stripes of different degrees of contrast (contrast sensitivity) and spatial frequencies. Following training, the lesion was made and the recovery of function was monitored. An initial rapid recovery was seen in parallel with a considerable resolution of optic nerve oedema. A less rapid recovery of the ability to recognize the thinner stripes was demonstrated over several months. Histological analysis showed that this recovery could occur even when up to 77% of optic nerve fibres were destroyed. In the absence of any known alternative anterior visual pathways these results suggest that adaptive changes in the brain must contribute to visual recovery after optic nerve damage. The possible role of cortical adaptation in recovery from demyelination in humans has not been widely studied, in part due to a lack of available techniques to investigate brain function, but also because of the considerable methodological difficulties in applying them to a multifocal, variable and often progressive disease like MS.