RESUMEN
Hereditary optic neuropathies (HON) - a group of neurodegenerative diseases characterized by primary loss of structure and function of the retinal ganglion cells and subsequent death of their axons, development of partial optic nerve atrophy. Autosomal dominant optic neuropathy and Leber`s hereditary optic neuropathy until recently were considered the most common genetic hereditary optic neuropathies, while autosomal recessive optic neuropathies (ARON) were described as rare types of HON, usually accompanying severe syndromic pathologies. In the 2000s it has become clear that ARON occur significantly more often, are underestimated, and their clinical variability is poorly studied. Despite the fact that non-syndromic ARON are less common than syndromic optic neuropathies, their contribution to the development of isolated hereditary optic neuropathies should be considered. This article presents a literature review on non-syndromic ARON developing as a result of mutations in the ACO2, MCAT, WFS1, RTN4IP1, TMEM126A, NDUFS2, DNAJC30 genes.
Asunto(s)
Atrofia Óptica Hereditaria de Leber , Atrofia Óptica , Enfermedades del Nervio Óptico , Humanos , Enfermedades del Nervio Óptico/diagnóstico , Enfermedades del Nervio Óptico/genética , Atrofia Óptica Hereditaria de Leber/diagnóstico , Atrofia Óptica Hereditaria de Leber/genética , Nervio Óptico/patología , Mutación , ADN Mitocondrial , Proteínas Portadoras/genética , Proteínas Mitocondriales/genética , Proteínas de la Membrana/genéticaRESUMEN
Folate metabolism disorders are known to have a potential involvement in the pathophysiology of mitochondrial diseases. Many researchers suggest that profound systemic folate deficiency may contribute to mitochondrial folate deficiency. Folic acid metabolism is closely related to vitamin B12 and homocysteine. Considering that hereditary optic neuropathies (HON) are mitochondrial diseases, it is important to study the folate status, the content of vitamin B12 and homocysteine in patients with this pathology. OBJECTIVE: To compare the content of folic acid, vitamin B12 and homocysteine in the blood serum of patients with Leber's hereditary optic neuropathy (LHON) and autosomal recessive optic neuropathy (ARON), optic neuropathy of other genesis, and the comparison group. MATERIAL AND METHODS: The study involved 58 patients with LHON and ARON, the control group of 49 patients with ischemic, inflammatory, traumatic and compressive optic neuropathies, and the comparison group of 20 healthy volunteers. RESULTS: A decrease in blood folic acid levels was revealed (4.0±1.6 ng/mL) in patients with HON compared to the control group (p=1.3·10-8) and the comparison group (p=1·10-17). The content of vitamin B12 in patients with HON was 380.8±168.1 pg/mL, which was significantly lower than in the comparison group (p=0.0001). The homocysteine content was 14.1±5.6 µmol/L in patients with HON, which was significantly higher than in the control group (p=0.0007) and the comparison group (p=0.000003). At the same time, an increase in homocysteine level of more than 10 µmol/L was revealed in 75% of patients with HON. Similar metabolic disorders were found in groups with various mutations in mitochondrial and nuclear DNA. CONCLUSION: Patients with HON showed marked decrease in the levels of folic acid and vitamin B12, as well as hyperhomocysteinemia. It is very important to identify the causes of metabolic disorders in order to determine the role of folate deficiency in the development of HON, as well as the possibility of its pharmacological treatment.
Asunto(s)
Deficiencia de Ácido Fólico , Hiperhomocisteinemia , Atrofia Óptica Hereditaria de Leber , Enfermedades del Nervio Óptico , Ácido Fólico , Deficiencia de Ácido Fólico/complicaciones , Deficiencia de Ácido Fólico/diagnóstico , Homocisteína , Humanos , Hiperhomocisteinemia/complicaciones , Hiperhomocisteinemia/diagnóstico , Atrofia Óptica Hereditaria de Leber/diagnóstico , Enfermedades del Nervio Óptico/diagnóstico , Enfermedades del Nervio Óptico/etiología , VitaminasRESUMEN
PURPOSE: To study the capabilities of electrophysiological and psychophysical examination methods for assessment of the functional state of ganglion cells, retina and optic nerve in patients with hereditary optic neuropathy (HON). MATERIAL AND METHODS: The study included 60 patients (118 eyes) with a genetically confirmed diagnosis of HON. All study patients underwent visual field test (VFT), spectral optical coherence tomography (OCT), flash and pattern visual evoked potentials (VEP) (Flash-VEP, FVEP; Pattern-VEP, PVEP), photopic electroretinography with photonegative response (PhNR) registration and the color vision test. In 24 patients (46 eyes), these parameters were assessed before the start of treatment and one year later. The treatment involved the mitochondria-targeted antioxidant SkQ1 - plastoquinonyl-decyl-triphenylphosphonium bromide (PDTP) in the form of eye drops. RESULTS: The main PVEP components for 1.0° and 0.3° were registered in 20% and in 14% of patient eyes with HON and high visual functions, respectively. After one year of PDTP use, a significant decrease in P100 peak latency was found only in the group with disease duration of ≤1.5 years as of the time of treatment start (p<0.05). Significant differences were observed in the PhNR amplitude (p<0.004) between patients of the main and the control groups, as well as in the PhNR amplitude between patients with visual acuity of ≤0.1 and ≥0.13 (p<0.01). Patients with high visual functions were found to have a correlation between the PhNR amplitude, GCC thickness and the global loss index (GLV). CONCLUSION: Along with VFT, OCT and color vision tests, electrophysiological studies are one of the main methods of examining patients with HON. After one year of PDTP use, there was a significant decrease in the FVEP P2 peak latency in the group with a disease duration of ≤1.5 years as of the time of treatment start. The PhNR amplitude in patients with high visual functions was found to correlate with structural changes in the ganglion cell layer and the retinal nerve fiber layer.
Asunto(s)
Potenciales Evocados Visuales , Enfermedades del Nervio Óptico , Electrorretinografía/métodos , Humanos , Enfermedades del Nervio Óptico/diagnóstico , Enfermedades del Nervio Óptico/etiología , Tomografía de Coherencia Óptica , Pruebas del Campo VisualRESUMEN
PURPOSE: To investigate the features of various parameters of the density of retinal blood vessels, optic nerve head (ONH) and peripapillary region in hereditary optic neuropathy (HON) patients revealed with optical coherence tomography angiography (OCTA). MATERIAL AND METHODS: The study included 29 HON patients divided into three groups based on symptoms duration (less than 1 year; 1-5 years, more than 5 years) and visual acuity (0.5-1.0; 0.04-0.4; 0.03 and lower). Relative macular, optic disc and peripapillary vessel density (VD, %) was assessed by OCTA (xR Avanti, Optovue Inc., USA). RESULTS: Significant progressive VD reduction in superficial capillary plexus (SCP) was detected in all parafovea sectors and in the temporal sector of perifovea over the course of disease progression. No significant differences of these parameters were found in correlation with visual acuity. Patients with VA of 0.5-1.0 turned out to have greater VD in deep capillary plexus (DCP), whereas no differences were found in relation to the duration of HON. A strong significant correlation between the SCP and DCP VD only in central foveal area was revealed in all groups depending on the VA and symptoms duration. Over the course of HON progression, VD in the temporal sector and in temporal segments of superior and inferior sectors has gradually reduced. In patients with VA of 0.5-1.0, the retinal nerve fibers layer (RNFL) thickness in the temporal sector and optic nerve VD was notably greater compared to patients with lower VA. The most significant correlation was established between VA and structural changes (K=0.75, p<0.001) and VD in the temporal sector (K=0.57-0.61, p<0.001). CONCLUSION: The obtained data suggest that derivative microvascular changes play an active role in the clinical progression of the disease.
Asunto(s)
Atrofia Óptica Hereditaria de Leber , Disco Óptico , Angiografía con Fluoresceína , Humanos , Vasos Retinianos , Tomografía de Coherencia ÓpticaRESUMEN
PURPOSE: To identify the specifics of structural and functional changes in patients with toxic optical neuropathy caused by acute methanol poisoning. MATERIAL AND METHODS: One female patient with toxic optic neuropathy (TON), 2 male patients with partial optic atrophy caused by methanol poisoning, and 1 male patient with methanol intoxication after ethanol containing alcohol use were examined with kinetic perimetry and optical coherence tomography. RESULTS: Patients with TON caused by acute methanol poisoning were observed to have decreasing visual acuity to the extent of complete blindness. OCT follow-up studies revealed thinning of the retinal nerve fiber layer (RNFL) as well as formation of microcysts in the inner retinal layers, destruction of ellipsoid zone and outer segments of photoreceptors. The patient with methanol intoxication after use of ethanol containing alcohol had retained his visual functions; he was found to have microcysts and RNFL thinning during the first few months after the intoxication, but they were within normal range of OCT parameters. CONCLUSION: Patients with TON caused by acute methanol poisoning are common to have optic atrophy with either residual visual functions or complete blindness as well as microcysts formation, structural changes and destruction of the ellipsoid zone and outer segments of photoreceptors. In patient with methanol intoxication after use of ethanol, which is known to be an antidote, complete visual recovery was observed, although some microcystic changes and ganglion cells layer thinning were noted.