Vitamin B3 Supplementation for Optic Neuropathies: A Comprehensive Review.

Optic neuropathies, such as glaucoma, are some of the leading causes of irreversible blindness worldwide. There has been a lot of research for potential therapies that could attenuate and even reduce the impact of the pathological pathways that lead to the loss of retinal ganglion cells (RGCs). In recent years, vitamin B3 (nicotinamide) has gained some interest as a viable option for these neurodegenerative diseases due to its fundamental role in enhancing the mitochondria metabolism of the RGCs. This review focuses on elucidating the impact of vitamin B3 on retinal cells, especially when in a dysfunctional state like what happens in optic neuropathies, especially glaucoma. This review also summarizes the existing and future research on the clinical effects of vitamin B3 in these optic neuropathies, and determines appropriate recommendations regarding its dosing, efficacy, and eventual side effects.

The Role of NAD+ and Nicotinamide (Vitamin B3) in Glaucoma: A Literature Review.

Glaucoma is a collection of irreversible optic neuropathies which, if left untreated, lead to severe visual field loss. These diseases are a leading cause of blindness across the globe and are estimated to affect approximately 80 million people, particularly women and people of Asian descent (Quigley HA, Broman AT. 2006. Br J Ophthalmol 90: 262-267). This represents a major burden on healthcare systems worldwide. Recently, there has been increasing interest in the potential of nicotinamide (vitamin B3) as a novel option in the management of glaucoma. This review aims to analyse the currently available literature to determine whether there is evidence of an association between nicotinamide adenine dinucleotide (NAD+) and glaucomatous optic neuropathy, and whether nicotinamide has the potential to prevent or reverse these effects. The literature showed a strong connection between reduced NAD+ levels and retinal ganglion cell dysfunction through multiple different studies. There is also evidence of the positive effect of nicotinamide supplementation on retinal ganglion cell function in models of mouse glaucoma and in a study involving humans. Based on the literature findings, a recommendation has been made that more research into the efficacy, appropriate dosing, and potential side effects of nicotinamide supplementation is needed before it can be definitively determined whether it is appropriate for widespread prophylactic and therapeutic use against glaucoma in humans.

Visual loss and optic neuropathy in a patient with Klinefelter's syndrome, open-angle glaucoma, vitamin B12 (cobalamin) and folate deficiency.

A 54-year-old man with Klinefelter's syndrome presented to the neuro-ophthalmology clinic with progressive painless visual blurring in the right eye over 2 years. He was receiving intramuscular testosterone therapy for hypogonadism and hypromellose for dry eye. Acuity was reduced bilaterally, and the right optic nerve head appeared pale and asymmetrically cupped. Optical coherence tomography revealed loss of retinal nerve fibre layer thickness in the right eye and visual field testing showed a developing right-ring scotoma. Blood tests showed vitamin B12 and folate deficiencies and polycythaemia. The patient was managed with intramuscular hydroxocobalamin, oral folate administration and re-initiation of his glaucoma medication. In Klinefelter's syndrome, signs of comorbid deficiency can be masked by the polycythaemic effect of testosterone therapy. For patients on long-term testosterone therapy, such as those with Klinefelter's syndrome, we recommend baseline ophthalmic examination and assessment, including intraocular pressure measurement, pachymetry, gonioscopy and screening 24-2 visual field testing.

[Centrally acting cholinomimetics in the complex therapy of progressive glaucomatous optic neuropathy].

UNLABELLED: Many factors exist that are associated with higher risk of glaucoma progression. Arterial hypotension, low perfusion pressure, vasospastic syndrome, diabetes mellitus, myopia, etc. increase the need for neuroprotective therapy, which is aimed at stabilizing the pathological process and creating favorable conditions for maintaining visual functions. The aim of this study was to assess the therapeutic efficacy of Gliatilin as part of the complex treatment of progressive glaucomatous optic neuropathy. MATERIAL AND METHODS: A total of 240 patients were randomly selected and divided into 2 groups, 120 patients each. Both groups were matched for age, somatic comorbidity, and the gravity of the glaucomatous process. Patient age averaged 71.3±1.6 years. Advanced glaucoma prevailed in both groups: 70.0 and 76.6% correspondingly. Neuroprotective therapy included drugs from different pharmacological classes so that different aspects of pathogenesis were addressed. Apart from that, patients from Group I first received intravenous Gliatilin (1000 mg/4ml, 12--15 doses) and then switched to oral (1 capsule b.i.d. for 4 months). All patients underwent standard ophthalmic examination and static perimetry. RESULTS: No adverse effects were observed over the first two weeks of Gliatilin course, during which the patients stayed in the hospital. IOP level was normal and stable. Although neuroprotective therapy does not directly affect IOP, stability of the latter describes the dynamics of the glaucomatous process. When assessing changes in visual functions, particular attention was paid to the central visual field, foveolar and total light sensitivity, peripheral visual field, and MD and PSD indices. All mean values showed a tendency toward improvement, more pronounced in the Gliatilin group. CONCLUSION: A complex therapy cannot be limited to a single drug only, and to make better decisions, one should consider not only ocular, but also general condition of the patient. Adjuvant Gliatilin in the complex therapy of progressive glaucoma is appropriate and efficient, especially in case of systemic atherosclerosis and cerebrovascular insufficiency. The frequency of stabilization therapy depends on the efficacy of the latest course and clinical manifestations of the glaucomatous process.

Neuroprotective effect of lignans extracted from Eucommia ulmoides Oliv. on glaucoma-related neurodegeneration.

Glaucoma is a progressive neurodegenerative disease, characterized by retinal ganglion cells (RGCs) and axon degeneration. The development of neuroprotective drug is required for improving the efficiency of glaucoma treatment. Eucommia ulmoides Oliv. has been used as a source of traditional medicine and as a beneficial health food. Lignans is one of the main bioactive components of Eucommia ulmoides. Here, we show that lignans protects RGCs against oxidative stress-induced injury in vitro. Moreover, lignans exerts neuroprotective effect on glaucoma-associated optic neuropathy in glaucomatous rats. Lignans treatment could improve oxidative stress response in RGCs and retinas of glaucomatous rats. Lignans plays an anti-oxidative stress role via the activation of AMPK signaling. This study provides evidence that lignans possesses protective effect on glaucoma-associated optic neuropathy. Lignans might be an alternative for the prevention and treatment of glaucomatous neurodegeneration.

[Optic neuropathy in a case of recurrent idiopathic hypertrophic pachymeningitis unresponsive to steroids and immunosuppressants]. / Neuropatía óptica en un caso de paquimeningitis hipertrófica idiopática recurrente sin respuesta a esteroides e inmunosupresores.

CASE REPORT: A 38-year-old female patient with bilateral papilledema who presented with loss of vision in her left eye. The Magnetic Resonance Imagining (MRI) showed thickening of the dura mater, and the intracranial pressure was elevated. A cancer, infectious, and autoimmune origin was ruled out. DISCUSSION: The initial response to high doses of corticoids was satisfactory, with disappearance of the optic disc enema, with visual acuity and an improvement in the MRI. However, after one year without treatment she had a new outbreak of the disease. Despite renewed treatment with corticoids and azathioprine, the patient developed a left optic neuropathy and irreversible visual loss.

[Options for correction of endothelial dysfunction and oxidative stress in patients with primary open-angle glaucoma].

OBJECTIVE: To evaluate the efficacy of Tanakan in patients with primary open-angle glaucoma (POAG) with respect to its influence on vascular endothelial function and oxidative stress. MATERIAL AND METHODS: Oxidative stress severity and antioxidant status were investigated in 52 patients with POAG divided into two groups. The effect of different treatment schemes on flow-dependent vasodilation and dynamic level of endotelin-1 (ET-1), which is a marker of endothelial dysfunction, was studied. RESULTS: In the main group glaucomatous optic neuropathy progressed significantly as compared to the baseline (p<0.05). A trend for a decrease in malondialdehyde-modified low-density lipoproteins (MDA-LDL) and plasma malondialdehyde (MDA) levels (p<0.1) was also found, which indicates the activation of antioxidant response and resolution of oxidative stress. Due to endothelial dysfunction, plasma ET-1 levels in glaucoma patients are on average 5 times higher than the corresponding median physiological concentration. After the treatment started plasma ET-1 levels reduced and 3 months later approached the normal range. Reactive hyperemia testing and assessment of flow-dependent vasodilation revealed a poor initial endothelial response in 64.6% of patients. During the treatment paradoxical vasoconstriction was noted in 12.4% of patients. After the treatment patients from the main group demonstrated a statistically significant increase in brachial artery diameter. CONCLUSION: Tanakan is showed to produce a positive effect on vascular remodeling in patients with POAG, which indicates its high antioxidant and antihypoxic activity. A significantly increased flow-dependent vasodilation found in the main group (especially 1-3 months after the beginning of the therapy) is thought to be due to an improved vasodilating ability of the vascular endothelium as the result of Tanakan use.

Bilateral consecutive optic neuropathy in a patient with thrombophilia.

A 39-year-old man was admitted with a sudden visual loss in the left eye. Visual acuities were 10/10 on the right and 1/10 on the left. Fundus examination did not show any abnormalities. Visual acuity improved to 10/10 and visual field defect regressed in the following 2 weeks. Three years later, the patient returned with acute visual loss in the right eye. Visual acuities were 2/10 on the right and 10/10 on the left. Right optic disc had blurred margins with mild oedema. The tests revealed methylenetetrahydrofolate reductase A1298C mutation with positive lupus anticoagulant and hyperhomocysteinaemia. Enoxaparin was initialised with vitamin B12 supplementation. Complete visual recovery occurred in the following 3 weeks in both eyes. Thrombophilic screening seems to be important in the treatment and prevention of an attack in the second eye of patients with non-arteritic anterior ischaemic optic neuropathy.

[Value of non-IOP lowering therapy for glaucoma]. / Stellenwert der "nicht Augendruck senkenden Glaukomtherapie"

It is well established that an IOP reduction improves, on average, the prognosis of all types of glaucoma. It is also known, however, that even an ideal IOP does not stop progression in all patients. The insight into the pathogenesis of glaucomatous damage leads to new therapeutic approaches. Whilst most of these new avenues of treatment are still in the experimental phase, others, such as magnesium, Ginkgo, salt and fludrocortisone are already used by some physicians. Blood pressure dips can be avoided by intake of salt or fludrocortisone. Vascular regulation can be improved either locally by carbonic anhydrase inhibitors or systemically with magnesium or with low doses of calcium channel blockers. A number of other food ingredients such as polyphenolic flavonoids occurring in tea, coffee, dark chocolate or red wine and anthocyanosides found in bilberries have potential antioxidative effects. The oxidative stress at the level of the mitochondria can be reduced by Ginkgo biloba. Experimentally, glaucomatous optic neuropathy can be prevented by inhibition of astrocyte activation, either by blockage of epidermal growth factor receptor or by counteracting endothelin. Glaucomatous optic neuropathy can also be prevented by nitric oxide-2 synthase inhibition. Inhibition of matrix metalloproteinase-9 inhibits apoptosis of retinal ganglion cells and tissue remodelling. Up-regulation of heat shock proteins protects the retinal ganglion cells and the optic nerve head.

Late-onset radiation-induced optic neuropathy after radiotherapy for nasopharyngeal carcinoma.

Radiation-induced optic neuropathy (RION) is a rare but devastating late complication of radiotherapy, usually manifesting months to years after cancer treatment of the head and neck, resulting in rapidly progressive blindness in one or both eyes. The incidence of radiation-induced complications following radiotherapy, especially RION, is correlated with survival time of patients. Nasopharyngeal carcinoma (NPC), the most common type of cancer in southern China, has been primarily treated with radiotherapy, with associated neural injuries. To our knowledge, there are few reports of RION among patients with NPC who have undergone radiotherapy. To study this further, we reviewed nine patients with NPC and RION after radiotherapy and examined the clinical manifestations of RION, characteristics of the ophthalmologic examination, MRI results and the treatments used. Of the nine patients with RION, the most frequent clinical presentation was a decline of vision with visual field defects in one or both eyes. Ophthalmologic examinations showed flame hemorrhages in the retina, optic nerve atrophy and cotton wool spots. T1-weighted enhanced MRI showed enhancement of the optic nerve and optic chiasm in six patients. Treatment with corticosteroids, anticoagulation and hyperbaric oxygen (HBO) treatment did not reduce visual loss or blindness in patients.

Erythropoietin treatment for methanol optic neuropathy.

BACKGROUND: To present the effect of erythropoietin for the treatment of methanol optic neuropathy. METHODS: Two patients with methanol optic neuropathy were treated with 10,000 IU of intravenous erythropoietin twice a day for 3 days, 500 mg of methylprednisolone twice a day for 5 days (followed by 2 weeks of oral prednisolone [1 mg/kg per day]), and daily doses of vitamin B12, vitamin B6, and folic acid for 1 month. RESULTS: At presentation, the patients had no perception of light in both eyes, associated with mildly swollen optic discs. Both responded dramatically to the treatment regimen. In the first patient, visual acuity improved to 20/20 in both eyes within 3 days, whereas in the second patient, visual acuity returned to counting fingers at 6 feet, right eye, and 20/30, left eye, within 3 weeks. CONCLUSION: Intravenous erythropoietin may be an effective adjuvant when combined with current treatment for patients with methanol optic neuropathy.

Ginkgo biloba: an adjuvant therapy for progressive normal and high tension glaucoma.

Gingko biloba has been used for hundreds of years to treat various disorders such as asthma, vertigo, fatigue and, tinnitus or circulatory problems. Two of the main extracts are EGb761 and LI 1370. Most pharmacological, toxicological and clinical studies have focused on the neuroprotective value of these two main extracts. Neuroprotection is a rapidly expanding area of research. This area is of particular interest due to the fact that it represents a new avenue of therapy for a frustrating disease that may progress despite optimal treatment. One such disease is glaucoma.Glaucoma leads to the loss of retinal ganglion cells and their axons but also to tissue remodelling which involves both the optic nerve head and the retina. In the retina the astrocytes get activated. In addition, the optic nerve gets thinner and the cells of the lateral geniculate ganglion disappear partially. On average, ocular blood flow (OBF) is reduced in glaucoma patients in various tissues of the eye. Increased intraocular pressure (IOP) is a major risk factor for glaucomatous damage. Nevertheless, there is little doubt that other risk factors besides IOP are involved. One such risk factor is a primary vascular dysregulation (PVD) occurring in patients with a disturbed autoregulation, another risk factor is oxidative stress.

Actualización en el tratamiento de la neuropatía óptica inflamatoria desmielinizante / Updating on the treatment of the demyelinating inflammatory optical neuropathy

Se realizó una revisión bibliográfica con el objetivo de proporcionar una actualización de las drogas que se emplean para retrasar la aparición de esclerosis múltiple en el manejo de la neuropatía óptica inflamatoria desmielinizante. El artículo presenta el origen y la justificación de la terapia esteroidea en este grupo de enfermedad, así como los mecanismos de acción y beneficios de tratamientos más modernos como los inmunomoduladores e inmunosupresores. El trabajo también introduce muchas de las drogas con efectos neuroprotectores que se encuentran en fases experimentales, cuyo uso prevendría la neurodegeneración que se produce a nivel de las células ganglionares retinianas en esta enfermedad neurológica. Las opciones terapéuticas actuales ofrecen variantes de tratamiento adicionales a pacientes con mayores probabilidades de desarrollo de esclerosis múltiple y retrasan la aparición de un segundo brote, así como las secuelas invalidantes que esta suele originar(AU)

A bibliographic review was conducted to provide an updating of drugs used to retard the appearance of multiple sclerosis in the management of the demyelinating inflammatory optical neuropathy. Present paper shows the origin and the justification of the steroid therapy in this disease, as well as the mechanisms of action and benefits of more recent treatments, e.g. the ongoing immunomodulations and immunosuppressive ones and also to introduce many drugs in experimental phase having neuroprotection effects whose use will prevent the neurodegenerative effect produced at level of the retinal ganglion cells in this neurologic disease. The current therapeutical options offer variants of additional treatment to those patients with greater possibilities to development multiple sclerosis and retarding the appearance of a second outbreak, as well as its disabling sequelae(AU)

Actualización en el tratamiento de la neuropatía óptica inflamatoria desmielinizante / Updating on the treatment of the demyelinating inflammatory optical neuropathy

Se realizó una revisión bibliográfica con el objetivo de proporcionar una actualización de las drogas que se emplean para retrasar la aparición de esclerosis múltiple en el manejo de la neuropatía óptica inflamatoria desmielinizante. El artículo presenta el origen y la justificación de la terapia esteroidea en este grupo de enfermedad, así como los mecanismos de acción y beneficios de tratamientos más modernos como los inmunomoduladores e inmunosupresores. El trabajo también introduce muchas de las drogas con efectos neuroprotectores que se encuentran en fases experimentales, cuyo uso prevendría la neurodegeneración que se produce a nivel de las células ganglionares retinianas en esta enfermedad neurológica. Las opciones terapéuticas actuales ofrecen variantes de tratamiento adicionales a pacientes con mayores probabilidades de desarrollo de esclerosis múltiple y retrasan la aparición de un segundo brote, así como las secuelas invalidantes que esta suele originar

A bibliographic review was conducted to provide an updating of drugs used to retard the appearance of multiple sclerosis in the management of the demyelinating inflammatory optical neuropathy. Present paper shows the origin and the justification of the steroid therapy in this disease, as well as the mechanisms of action and benefits of more recent treatments, e.g. the ongoing immunomodulations and immunosuppressive ones and also to introduce many drugs in experimental phase having neuroprotection effects whose use will prevent the neurodegenerative effect produced at level of the retinal ganglion cells in this neurologic disease. The current therapeutical options offer variants of additional treatment to those patients with greater possibilities to development multiple sclerosis and retarding the appearance of a second outbreak, as well as its disabling sequelae

Optic neuropathy in methylmalonic acidemia: the role of neuroprotection.

We report the case of a patient with an optic neuropathy induced by neurotoxicity in the setting of methylmalonic acidemia. The patient responded with a significant and long-term improvement in visual acuity, perimetry, and chromatic function after a neuroprotective treatment with vitamin E and coenzyme Q10 was started. Coenzyme Q10 levels had been proven to be normal before starting treatment. This case report is particularly important because it describes a possible treatment for optic neuropathy in methylmalonic patients. Although the response might be, in part, specific to the individual, it suggests the existence of a cause-effect relationship between the treatment undergone by our patient and the improvement in her visual acuity. To date, no other treatments with beneficial effects have been reported for the few optic neuropathies caused by methylmalonic acidemia. Further studies should determine the applicability of coenzyme Q10 and vitamin E for the treatment of optic neuropathies in methylmalonic acidemia.

Perry syndrome due to the DCTN1 G71R mutation: a distinctive levodopa responsive disorder with behavioral syndrome, vertical gaze palsy, and respiratory failure.

Perry syndrome is a rare form of autosomal dominant Parkinsonism with respiratory failure recently defined as being due to mutations in the DCTN1 gene. We describe a new family carrying a G71R mutation in the DCTN1 gene. The proband displayed a series of distinctive features not previously described in Perry syndrome: a disorder of vertical downward saccades accompanied by progressive midbrain atrophy, predominant nonmotor symptoms responsive to levodopa, distinctive craniocervical levodopa induced dyskinesias, and a good response to high-dose levodopa therapy and respiratory support. The family was initially thought to have autosomal dominant behavioral variant frontotemporal dementia with Parkinsonism. This report expands the clinical definition of this distinctive syndrome.

Respuesta a la idebenona asociada a multivitaminoterapia en neuropatía óptica hereditaria de Leber / Response to idebenone and multivitamin therapy in leber´s hereditary optic neuropathy

Objetivo: Determinar la eficacia del tratamiento con idebenona y multivitamínico en la neuropatía óptica hereditaria de Leber (NOHL). Método: Dos pacientes diagnosticados de NOHL, fueron tratados con idebenona, vitamina C y riboflavina durante un año. Ambos fueron evaluados clínicamente antes, durante y después del tratamiento. Resultado: Ninguno de los dos pacientes experimentó mejoría visual y ambos sufrieron afectación en el segundo ojo. Conclusiones: A pesar de casos publicados en la literatura de recuperación visual con idebenona en pacientes con NOHL, nuestra experiencia indica que este tratamiento no es efectivo para la enfermedad de Leber

Objective: To ascertain the efficacy of idebenone and multivitamin treatment in Leber’s hereditary optic neuropathy (LHON). Method: Two patients diagnosed of unilateral LHON were treated with megadoses of idebenone, vitamin C and riboflavin for one year. They were examined clinically before, during and after treatment. Results: No improvement of visual function was observed. Despite the idebenone treatment, in both cases the second eye became involved. Conclusions: Despite previous reports of visual recovery with idebenone in patients with LHON, our experience shows that an effective treatment for Leber’s disease remains to be found

[The efficiency of the use of cerebrolysin in optic nerve diseases in children of different age].

The purpose of the study was to evaluate the efficiency of cerebrolysin used in partial atrophies of the optic nerve in relation to the method of drug injection and to whether treatment was used in combination with percutaneous electrostimulation of the optic nerve. The study was based on the results of clinical and electrophysiological studies of 646 children (810 eyes) aged 8 weeks to 18 years. All the examinees were divided into 4 groups: 1) patients in whom cerebrolysin was administered as retrobulbar injections made once daily; 2) those in whom cerebrolysion was injected in combination with microcirculation-improving agents through the irrigation system into the retrobulbar and Tenon space; 3) patients who received cerebrolysin only through the irrigation system; 4) those in whom the agents affecting the microcirculatory bed in the optic nerve system were administered through the irrigation system. Cerobrolysin has turned out to be highly effective as a drug that improved the outcomes of percutaneous stimulation of the optic nerve due to the use of two-stage treatment of children with partial atrophy of the optic nerve of various genesis, involving irrigation therapy supplemented by cerebrolysin and vascular agents at the first stage and percutaneous stimulation of the optic nerve at the second one.

Configuration of the drainage angle, intraocular pressure, and optic disc cupping in subjects with chronic angle-closure glaucoma.

OBJECTIVE: To investigate the relationship between drainage angle configuration with untreated intraocular pressure (IOP) and optic disc cupping in subjects with chronic angle-closure glaucoma (CACG). DESIGN: Prospective, observational study. PARTICIPANTS: Two hundred seventy-five Asian subjects with CACG who participated in a randomized controlled trial that investigated the IOP-reducing effect of latanoprost and timolol. METHODS: Chronic angle-closure glaucoma was defined as the presence of glaucomatous optic neuropathy (with or without a visual field defect), an anterior chamber angle in which the pigmented trabecular meshwork was not visible for at least 180 degrees on gonioscopy, and evidence of peripheral anterior synechiae (PAS) in association with elevated IOP of 21 mmHg or more. Static and dynamic gonioscopy were performed, the angles were graded in each quadrant according to the Shaffer scheme, and the number of clock hours of PAS was recorded. The untreated IOP and vertical cup-to-disc ratio were correlated with mean angle width and extent of PAS. MAIN OUTCOME MEASURES: Mean angle width, clock hours of PAS, IOP, and vertical cup-to-disc ratio. RESULTS: Most subjects were female (75%), and the mean age was 62.9+/-9.4 years. The mean angle width was 0.77+/-0.53 and the mean number of clock hours of PAS was 4.77+/-3.2 hours. Untreated IOP correlated with angle width (r = -0.23; P<0.001) and clock hours of PAS (r = 0.22; P<0.001). Vertical cup-to-disc ratio also correlated with angle width (r = -0.17; P = 0.004) and PAS (r = 0.28; P<0.001). Performing a multiple linear regression using baseline IOP as the outcome variable with age, gender, clock hours of PAS, and angle width as predictors, there was a 0.39-mmHg (95% confidence interval, 0.15-0.63) increase in baseline untreated IOP for each unit increase in clock hours of PAS (P = 0.002). CONCLUSIONS: In subjects with CACG, the extent of PAS and a narrower width of the drainage angle were associated with higher untreated IOP and a larger vertical cup-to-disc ratio.

Optic neuropathy secondary to radiotherapy for nasal melanoma.

Optic neuropathy is a rare but important complication of radiotherapy used in the treatment of cancers of the head and neck, usually resulting in rapidly progressive blindness in one or both eyes. The case is presented of a 77-year-old woman with bilateral optic neuropathy resulting in blindness, secondary to radiotherapy for a melanoma of the nasal cavity. The onset of optic neuropathy occurred 9 months post-radiotherapy, at a cumulative dose of 6000 rad. The left eye was first involved, with the right eye becoming involved within 2 weeks. Despite treatment with oral anticoagulation and high dose intravenous methylprednisolone, there was progressive deterioration resulting in bilateral optic atrophy, with final visual acuities of perception of light in the right eye and no perception of light in the left eye. This case demonstrates that oral anticoagulation was ineffective in the treatment of progressive radiation-induced optic neuropathy.