Optical Coherence Tomography in Multiple Sclerosis and Neuromyelitis Optica: An Update

Optical coherence tomography (OCT) uses light interference patterns to produce a cross-sectional image of the retina. It is capable of measuring the unmyelinated axons of the retinal ganglionar cells as they converge on the optic disc. In a disease like multiple sclerosis (MS), in which axonal loss has been identified as an important cause of sustained disability, it may prove an invaluable tool. OCT has demonstrated that axonal loss occurs after each episode of optic neuritis and that the degree of axonal loss is correlated to visual outcomes. Furthermore, axonal loss occurs in MS even in the absence of inflammatory episodes, and the degree of this loss is correlated with the duration of the disease process, with more thinning as the disease advances and in progressive forms. Thus, OCT retinal nerve fiber layer measurements may represent an objective outcome measure with which to evaluate the effect of treatment

Molecular and genetic mechanism of non-syndromic congenital cataracts. Mutation screening in Spanish families

Our purpose was to identify mutations responsible for non-syndromic congenital cataracts through the implementation of next-generation sequencing (NGS) in our center. A sample of peripheral blood was obtained from probands and willing family members and genomic DNA was extracted from leukocytes. DNA was analyzed implementing a panel (OFTv2.1) including 39 known congenital cataracts disease genes. 62 probands from 51 families were recruited. Pathogenic or likely pathogenic variants were identified in 32 patients and 25 families; in 16 families (64%) these were de novo mutations. The mutation detection rate was 49%. Almost all reported mutations were autosomal dominant. Mutations in crystallin genes were found in 30% of the probands. Mutations in membrane proteins were detected in seven families (two in GJA3 and five in GJA8). Mutations in LIM2 and MIP were each found in three families. Other mutations detected affected EPHA2, PAX6, HSF4 and PITX3. Variants classified as of unknown significance were found in 5 families (9.8%), affecting CRYBB3, LIM2, EPHA2, ABCB6 and TDRD7. Mutations lead to different cataract phenotypes within the same familyThis research was funded by ONCE grant number 2020/0197782 and by FIS grant number PI18-1234-ISCII

Clinically Isolated Syndromes Suggestive of Multiple Sclerosis: An Optical Coherence Tomography Study

Background: Optical coherence tomography (OCT) is a simple, high-resolution technique to quantify the thickness of retinal nerve fiber layer (RNFL), which provides an indirect measurement of axonal damage in multiple sclerosis (MS). This study aimed to evaluate RNFL thickness in patients at presentation with clinically isolated syndromes (CIS) suggestive of MS. Methodology: This was a cross-sectional study. Twenty-four patients with CIS suggestive of MS (8 optic neuritis [ON], 6 spinal cord syndromes, 5 brainstem symptoms and 5 with sensory and other syndromes) were prospectively studied. The main outcome evaluated was RNFL thickness at CIS onset. Secondary objectives were to study the relationship between RNFL thickness and MRI criteria for disease dissemination in space (DIS) as well as the presence of oligoclonal bands in the cerebrospinal fluid. Principal Findings: Thirteen patients had decreased RNFL thickness in at least one quadrant. Mean RNFL thickness was 101.67±10.72 μm in retrobulbar ON eyes and 96.93±10.54 in unaffected eyes. Three of the 6 patients with myelitis had at least one abnormal quadrant in one of the two eyes. Eight CIS patients fulfilled DIS MRI criteria. The presence of at least one quadrant of an optic nerve with a RNFL thickness at a P<5% cut-off value had a sensitivity of 75% and a specificity of 56% for predicting DIS MRI. Conclusions: The findings from this study show that axonal damage measured by OCT is present in any type of CIS; even in myelitis forms, not only in ON as seen up to now. OCT can detect axonal damage in very early stages of disease and seems to have high sensitivity and moderate specificity for predicting DIS MRI. Studies with prospective long-term follow-up would be needed to establish the prognostic value of baseline OCT finding

Late Optic Neuropathy in Propionic Acidemia Following Surgical Intervention

Late Optic Neuropathy in Propionic Acidemia Following Surgical Intervention Traber et al (1) recently reported a case of "Subacute bilateral visual loss in methylmalonic acidemia" in a 23-year-old woman. Late-onset optic nerve damage has been described only rarely in organic acidemias. We present a similar case in propionic acidemia

Expanding the Phenotypic Spectrum of PAX6 Mutations: From Congenital Cataracts to Nystagmus

Background: Congenital aniridia is a complex ocular disorder, usually associated with severe visual impairment, generally caused by mutations on the PAX6 gene. The clinical phenotype of PAX6 mutations is highly variable, making the genotype–phenotype correlations difficult to establish. Methods: we describe the phenotype of eight patients from seven unrelated families with confirmed mutations in PAX6, and very different clinical manifestations. Results: Only two patients had the classical aniridia phenotype while the other two presented with aniridia-related manifestations, such as aniridia-related keratopathy or partial aniridia. Congenital cataracts were the main manifestation in three of the patients in this series. All the patients had nystagmus and low visual acuity. Conclusions: The diagnosis of mild forms of aniridia is challenging, but these patients have a potentially blinding hereditary disease that might present with a more severe phenotype in future generations. Clinicians should be aware of the mild aniridia phenotype and request genetic testing to perform an accurate diagnosis

Automated Evaluation of Choroidal Thickness and Minimum Rim Width Thickness in Nonarteritic Anterior Ischemic Optic Neuropathy

The aim of this study was to evaluate and compare peripapillary choroidal thickness (pCT) and macular choroidal thickness (CT), Bruch membrane opening-minimum rim width (BMO-MRW), retinal nerve fiber layer (RNFL) thickness, and optic disc area among nonarteritic anterior ischemic optic neuropathy (NAION) eyes, the contralateral unaffected eyes, and healthy control eyes.; Twenty-six patients diagnosed with NAION (29 affected and 21 unaffected eyes) and 29 healthy matched control individuals (29 eyes) were analyzed by swept-source optical coherence tomography. All participants underwent scanning by Spectralis optical coherence tomography to analyze BMO-MRW, RNFL thickness, and optic disc area.; Mean pCT in the NAION eyes, unaffected fellow eyes, and the control group was 130.5 ± 72.1 μm, 149.6 ± 75.7 μm, and 103.7 ± 36.7 μm, respectively (analysis of variance [ANOVA], P = 0.04). Mean macular CT in the NAION eyes, unaffected fellow eyes, and the control group was 226.1 ± 79.8 μm, 244.6 ± 81.4 μm, and 189.9 ± 56.4 μm, respectively (ANOVA, P = 0.03). Mean and all sectorial RNFL and BMO-MRW thickness values were significantly thinner in the NAION eyes vs the unaffected fellow and control eyes (P ≤ 0.00). The unaffected fellow eyes in NAION patients showed a significantly thicker average and sectorial BMO-MRW values than control eyes (P ≤ 0.02) except for the nasal sector (P = 0.09). Mean optic disc area derived from BMO analysis was not significantly different among groups (ANOVA, P = 0.86).; The fellow unaffected eyes in patients with NAION showed significantly thicker mean peripapillary and macular choroidal and BMO-MRW thicknesses than disease-free control eyes. No differences in the mean optic disc area were found. Both a thick peripapillary choroid and a thick neuroretinal rim might contribute to the development of NAION or possibly be a secondary phenomenon