Carlos E. Mendoza-Santiesteban

Optical coherence tomography of the retina: applications in neurology.

Purpose of reviewThis review summarizes the mechanisms and recent developments of optical coherence tomography and its practical uses in neurology. The application of optical coherence tomography imaging of the retina in multiple sclerosis, neuromyelitis optica, Alzheimer disease, and Parkinson disease are reviewed. Recent findingsThinning of the peripapillary retinal nerve fibre layer has been detected in patients with optic neuritis, multiple sclerosis, neuromyelitis optica, Alzheimer disease, and Parkinson disease. However, the patterns of change differ in some aspects. SummaryThe findings indicate loss of retinal ganglion cells and may reflect degenerative change in the brain in these conditions. The retinal nerve fibre layer thickness may be used as a biological marker and may help to distinguish between optic neuritis associated with multiple sclerosis and optic neuritis in neuromyelitis optica.

Subretinal Fluid From Anterior Ischemic Optic Neuropathy Demonstrated by Optical Coherence Tomography

OBJECTIVE To demonstrate the development of subfoveal fluid associated with optic disc swelling from nonarteritic anterior ischemic optic neuropathy. METHODS Optical coherence tomographic studies obtained during a 3-year period (October 1, 2003, to December 30, 2006) from 76 patients who developed ischemic optic neuropathy from 2 institutions were evaluated. The presence or absence, and the distribution, of subretinal fluid was determined. RESULTS Seventy-six patients underwent macular optical coherence tomography within 4 weeks of developing sudden loss of vision in one eye, decreased visual acuity, a visual field defect, a relative afferent pupillary defect, and optic disc swelling with peripapillary hemorrhages. Eight patients had apparent subretinal fluid extending into the subfoveal space. Visual acuity improved in 5 of the 8 patients as the subfoveal fluid resolved. CONCLUSIONS Subretinal fluid develops in some patients with nonarteritic anterior ischemic optic neuropathy and may contribute to some of the visual loss associated with this condition. Furthermore, resolution of the subretinal fluid could account for some of the visual improvement that can follow anterior ischemic optic neuropathy.

Current treatments in familial dysautonomia

Introduction: Familial dysautonomia (FD) is a rare hereditary sensory and autonomic neuropathy (type III). The disease is caused by a point mutation in the IKBKAP gene that affects the splicing of the elongator-1 protein (ELP-1) (also known as IKAP). Patients have dramatic blood pressure instability due to baroreflex failure, chronic kidney disease, and impaired swallowing leading to recurrent aspiration pneumonia, which results in chronic lung disease. Diminished pain and temperature perception result in neuropathic joints and thermal injuries. Impaired proprioception leads to gait ataxia. Optic neuropathy and corneal opacities lead to progressive visual loss. Areas covered: This article reviews current therapeutic strategies for the symptomatic treatment of FD, as well as the potential of new gene-modifying agents. Expert opinion: Therapeutic focus on FD is centered on reducing the catecholamine surges caused by baroreflex failure. Managing neurogenic dysphagia with effective protection of the airway passages and prompt treatment of aspiration pneumonias is necessary to prevent respiratory failure. Sedative medications should be used cautiously due to the risk of respiratory depression. Non-invasive ventilation during sleep effectively manages apneas and prevents hypercapnia. Clinical trials of compounds that increase levels of IKAP (ELP-1) are underway and will determine whether they can reverse or slow disease progression.

Clinical neuro-ophthalmic findings in familial dysautonomia.

Background To define the clinical neuro-ophthalmic abnormalities of patients with familial dysautonomia (FD). Methods Sixteen patients (32 eyes) with the clinical and molecular diagnoses of FD underwent thorough neuro-ophthalmic clinical evaluation. Results Visual acuity ranged from 0.05 to 1.0 decimal units and was reduced in 15 of 16 patients. Mild to moderate corneal opacities were found in most patients but were visually significant in only 2 eyes. Red-green color vision was impaired in almost all cases. Depression of the central visual fields was present on automated visual fields in all patients, even in those with normal visual acuity. Temporal optic nerve pallor was present in all cases and was associated with retinal nerve fiber layer loss in the papillomacular region. Various ocular motility abnormalities also were observed. Conclusion Patients with FD have a specific type of optic neuropathy with predominant loss of papillomacular nerve fibers, a pattern similar to other hereditary optic neuropathies caused by mutations either in nuclear or in mitochondrial DNA, affecting mitochondrial protein function. Defects of eye movements, particularly saccades, also appear to be a feature of patients with FD.

Progressive retinal structure abnormalities in multiple system atrophy

Objective measures of disease progression that can be used as endpoints in clinical trials of MSA are necessary. We studied retinal thickness in patients with MSA and assessed changes over time to determine its usefulness as an imaging biomarker of disease progression.

Optical coherence tomography shows retinal abnormalities associated with optic nerve disease

Optical coherence tomography (OCT) of the macula in patients with primary optic neuropathy has revealed the presence of structural changes in the neurosensory retina in addition to the nerve fibre layer. Subretinal fluid has been documented in papilloedema and non-arteritic ischaemic optic neuropathy, and may account for decreased visual acuity in affected patients. Subretinal fluid has also been described from other causes of optic nerve head swelling including diabetic papillopathy and papillitis. Drugs used in the treatment of multiple sclerosis, such as corticosteroids and fingolimod can cause decreased vision due to central serous and cystoid macular oedema sometimes confused with recurrent optic neuritis. A subset of patients with various types of optic atrophy show microcystic changes in the inner nuclear layer on spectral domain OCT imaging. The pathophysiology and visual significance of these retinal changes remain unclear, but may affect the diagnosis and management of optic nerve disorders.

Optical coherence tomography for neuro-ophthalmologic diagnoses.

OCT is probably one of the most revolutionary technologies that has appeared in ophthalmology in recent years. We are still trying to understand and clarify the use of OCT in neuro-ophthalmology. In this article we share our experience using various OCT devices over the last ten years, as well as the experience of others as reported in the literature.

Optical Coherence Tomography Angiography in Nonarteritic Anterior Ischemic Optic Neuropathy.

Background: Optical coherence tomography angiography (OCTA) has demonstrated good utility in qualitative analysis of retinal and choroidal vasculature and therefore may be relevant in the diagnostic and treatment efforts surrounding nonarteritic anterior ischemic optic neuropathy (NAION). Methods: Retrospective, cross-sectional study of 10 eyes of 9 patients with a previous or new diagnosis of NAION that received imaging with OCTA between November 2015 and February 2016. Two independent readers qualitatively analyzed the retinal peripapillary capillaries (RPC) and peripapillary choriocapillaris (PCC) for flow impairment. Findings were compared with automated visual field and structural optical coherence tomography (OCT) studies. Results: Flow impairment seen on OCTA in the RPC corresponded to structural OCT deficits of the retinal nerve fiber layer (RNFL) and ganglion cell layer complex (GCC) in 80% and 100% of eyes, respectively, and to automated visual field deficits in 90% of eyes. Flow impairment seen on OCTA in the PCC corresponded to structural OCT deficits of the RNFL and GCC in 70% and 80% of eyes, respectively, and to visual field deficits in 60%–80% of eyes. Conclusions: OCTA can noninvasively visualize microvascular flow impairment in patients with NAION.

Pathological Confirmation of Optic Neuropathy in Familial Dysautonomia

Clinical data suggest that optic neuropathy and retinal ganglion cell loss are the main cause of visual decline in patients with familial dysautonomia, but this has not previously been confirmed by pathological analyses. We studied retinas and optic nerves in 6 eyes from 3 affected patients obtained at autopsy. Analyses included routine neurohistology and immunohistochemistry for neurofilaments, cytochrome c oxidase (COX), and melanopsin-containing ganglion cells. We observed profound axon loss in the temporal portions of optic nerves with relative preservation in the nasal portions; this correlated with clinical and optical coherence tomography findings in 1 patient. Retinal ganglion cell layers were markedly reduced in the central retina, whereas melanopsin-containing ganglion cells were relatively spared. COX staining was reduced in the temporal portions of the optic nerve indicating reduced mitochondrial density. Axonal swelling with degenerating lysosomes and mitochondria were observed by electron microscopy. These findings support the concept that there is a specific optic neuropathy and retinopathy in patients with familial dysautonomia similar to that seen in other optic neuropathies with mitochondrial dysfunction. This raises the possibility that defective expression of the IkB kinase complex-associated protein (IKAP) resulting from mutations in IKBKAP affects mitochondrial function in the metabolism-dependent retinal parvocellular ganglion cells in this condition.

Ganglion Cell Complex Loss in Chiasmal Compression by Brain Tumors

Background: Patterns of ganglion cell complex (GCC) loss detected by optical coherence tomography provide an objective measure of optic nerve injury. These patterns aid in early diagnosis and localization of chiasmal lesions. Methods: Twenty-three patients with chiasmal compression seen between 2010 and 2015 were imaged with the Cirrus high-definition optical coherence tomography macular cube 512 × 128, retinal nerve fiber layer (RNFL) scan protocols and automated (30-2 Humphrey) visual fields (VFs). Age-matched controls were included for comparison. Generalized estimating equations were performed comparing RNFL and GCC thicknesses between patients and their controls. Effect size (d) was calculated to assess the magnitude of difference between patients and controls. The average GCC and RNFL thicknesses also were correlated with VF mean deviation (MD). Pre operative average GCC thickness was correlated to post operative VF MD. Results: Patterns of GCC thinning corresponded to VF defects. The average GCC thickness was 67 ± 9 &mgr;m in patients and 86 ± 5 &mgr;m in controls (P < 0.001). The effect size was the greatest for GCC thickness (d = 2.72). The mean deviation was better correlated with GCC thickness (r2 =0.25) than RNFL thicknesses (r2 =0.15). Postoperatively, VF MD improved in 7 of 8 patients with persistent nasal GCC thinning. Six patients had no VF defect and showed statistically significant loss of GCC compared with controls (P = 0.001). Conclusions: Distinct patterns of GCC loss were identified in patients with chiasmal compression. Binasal GCC loss was typical and could be seen with minimal or no detectable VF loss. Thinning of the GCC may be detected before loss of the RNFL in some patients. After decompression, the majority of patients showed improvement in VF despite persistent GCC loss. Patients with less GCC loss before decompression had better postoperative VFs. Therefore, GCC analysis may be an objective method to diagnose and follow patients with chiasmal lesions.