Visual dysfunction in macular telangiectasia type 2

Macular telangiectasia type 2 (macular telangiectasia type 2) is a bilateral neurodegenerative condition of the macula of the human eye which can lead to loss of central vision. There is evidence that metabolic dysfunction leads to slow degeneration of the retinal neuroglia, eventually leading to circumscribed loss of neuronal tissue (photoreceptor atrophy). A characteristic feature of macular telangiectasia type 2 is the temporal epicenter where the disease typically begins, and its limitation to a central oval shaped area of approximately five by ten degrees, called the macular telangiectasia type 2 area. Knowledge about visual function of people with macular telangiectasia type 2 was limited to visual acuity testing, investigations of reading performance, visual field testing with fundus-controlled perimetry (microperimetry), and scotopic perimetry (not fundus-controlled). This thesis summarises research aimed at exploring visual function in macular telangiectasia type 2 in more detail. In particular, visual acuity and reading performance are investigated in more detail, the (para)central scotomas are better characterised, and visual function in low light is elucidated by testing contrast sensitivity, low luminance visual acuity and dark-adapted microperimetry. Visual acuity data was collected as part of the international research collaboration The macular telangiectasia type 2 study, which started in 2005 and has since then accrued data of more than 3000 individuals with macular telangiectasia type 2. It was taken with Early Treatment of Diabetic Retinopathy Study (ETDRS) charts on a harmonised protocol. Distribution of visual acuity in the entire study cohort was investigated and eyes with low visual acuity were looked at in detail. It was found that only about half of eyes with very poor visual acuity showed evidence of neovascularisations, until recently still considered disease end stage, but nearly all eyes showed photoreceptor atrophy, which is therefore more likely to define the disease end stage. Scotomas were characterised further on retrospective analysis of microperimetry examinations from four large centers of the macular telangiectasia type 2 study. This analysis confirmed previous data which suggested mono-focality of the scotomas and the limitation to a specific size. Further microperimetry assessment was performed with a recently introduced new technology, allowing dark-adapted microperimetry with two wavelengths, aiding differentiation of cone and rod dysfunction. This test showed more general sensitivity reduction for blue light under low light conditions. This may be in keeping with the findings from contrast sensitivity testing in mesopic light conditions, showing strong impairment already in early disease stages, possibly indicating inner retinal dysfunction rather than photoreceptor dysfunction in those disease stages. Reading performance and the effect of binocularity was measured with Radner Reading charts. Reading was consistently slower when patients were using both eyes, strongly indicating binocular inhibition, in particular when arising from scotomas in left eyes. Based on the above, the findings resulted in new insights into visual function with implications on our understanding of the condition. Understanding visual impairment not only helps patient counselling, but also helps driving directions of future research

Intraretinal pigmented cells in retinal degenerative disease

PURPOSE: Invasion of pigmented cells into the retina occurs in retinal degenerative diseases, such as macular telangiectasia type 2 (MacTel) and retinitis pigmentosa (RP). These intraretinal pigmented cells may be derived from the retinal pigment epithelium (RPE), but differences and similarities between intraretinal pigmented cells and RPE have so far not been well characterised.Clinicopathologic case report. METHOD: Here, we compared intraretinal pigment cells with RPE cells by immunohistochemistry. Immunohistological stains for classic RPE markers (RPE65, CRALBP and KRT18) and blood vessel markers (lectin and collagen 4) were done on sections from postmortem eye tissue from two MacTel donors, an RP donor and a control donor. MAIN OUTCOME MEASURES: Presence of specific immunohistochemistry markers on intraretinal pigmented and RPE cells. RESULTS: We found that intraretinal pigmented cells did not express RPE65 and CRALBP, with a small subset expressing them weakly. However, they all expressed KRT18, which was also present in normal RPE cells. Interestingly, we also found clusters of KRT18-positive cells in the retina that were not pigmented. CONCLUSIONS: Our findings suggest that RPE cells invading the retina dedifferentiate (losing classic RPE markers) and can be pigmented or unpigmented. Therefore, the number of RPE cells invading the retina in retinal degenerative disease may be underappreciated by funduscopy

High-resolution in vivo fundus angiography using a non-adaptive optics imaging system

Purpose: We provide a proof of concept for the detailed characterization of retinal capillary features and surrounding photoreceptor mosaic using a customized nonadaptive optics angiography imaging system. Methods: High-resolution fluorescein angiography (FFA) and/or indocyanine green angiography (ICGA) images were obtained using a modified Heidelberg retina angiograph (HRA2) device with a reduced scan angle enabling 3° field of view. Colocalized images of the photoreceptor mosaic also were captured in vivo using the same instrument. Visibility of vascular subbranches were compared between high-resolution images and conventional fundus angiography (FA) with a 30° field of view. Results: High-resolution angiographic and infrared images (3° × 3° field of view, a 10-fold magnification) were obtained in 10 participants. These included seven patients with various retinal diseases, including myopic degeneration, diabetic retinopathy, macular telangiectasia, and central serous chorioretinopathy, as well as three healthy controls. Images of the retinal vasculature down to the capillary level were obtained on angiography with the ability to visualize a mean 1.2 levels more subbranches compared to conventional FA. In addition, imaging of the photoreceptor cone mosaic, to a sufficient resolution to calculate cone density, was possible. Movement of blood cells within the vasculature also was discernible on infrared videography. Conclusions: This exploratory study demonstrates that fast high-resolution angiography and cone visualization is feasible using a commercially available imaging system. Translational Relevance: This offers potential to better understand the relationship between the retinal neurovascular system in health and disease and the timing of therapeutic interventions in disease states

Validation of automated artificial intelligence segmentation of optical coherence tomography images

PURPOSE To benchmark the human and machine performance of spectral-domain (SD) and swept-source (SS) optical coherence tomography (OCT) image segmentation, i.e., pixel-wise classification, for the compartments vitreous, retina, choroid, sclera. METHODS A convolutional neural network (CNN) was trained on OCT B-scan images annotated by a senior ground truth expert retina specialist to segment the posterior eye compartments. Independent benchmark data sets (30 SDOCT and 30 SSOCT) were manually segmented by three classes of graders with varying levels of ophthalmic proficiencies. Nine graders contributed to benchmark an additional 60 images in three consecutive runs. Inter-human and intra-human class agreement was measured and compared to the CNN results. RESULTS The CNN training data consisted of a total of 6210 manually segmented images derived from 2070 B-scans (1046 SDOCT and 1024 SSOCT; 630 C-Scans). The CNN segmentation revealed a high agreement with all grader groups. For all compartments and groups, the mean Intersection over Union (IOU) score of CNN compartmentalization versus group graders' compartmentalization was higher than the mean score for intra-grader group comparison. CONCLUSION The proposed deep learning segmentation algorithm (CNN) for automated eye compartment segmentation in OCT B-scans (SDOCT and SSOCT) is on par with manual segmentations by human graders

Safety and Feasibility of a Novel Sparse Optical Coherence Tomography Device for Patient-Delivered Retina Home Monitoring

Purpose To study a novel and fast optical coherence tomography (OCT) device for home-based monitoring in age-related macular degeneration (AMD) in a small sample yielding sparse OCT (spOCT) data and to compare the device to a commercially available reference device. Methods In this prospective study, both eyes of 31 participants with AMD were included. The subjects underwent scanning with an OCT prototype and a spectral-domain OCT to compare the accuracy of the central retinal thickness (CRT) measurements. Results Sixty-two eyes in 31 participants (21 females and 10 males) were included. The mean age was 79.6 years (age range, 69-92 years). The mean difference in the CRT measurements between the devices was 4.52 μm (SD ± 20.0 μm; range, -65.6 to 41.5 μm). The inter- and intrarater reliability coefficients of the OCT prototype were both >0.95. The laser power delivered was <0.54 mW for spOCT and <1.4 mW for SDOCT. No adverse events were reported, and the visual acuity before and after the measurements was stable. Conclusion This study demonstrated the safety and feasibility of this home-based OCT monitoring under real-life conditions, and it provided evidence for the potential clinical benefit of the device. Translational Relevance The newly developed spOCT is a valid and readily available retina scanner. It could be applied as a portable self-measuring OCT system. Its use may facilitate the sustainable monitoring of chronic retinal diseases by providing easily accessible and continuous retinal monitoring

A Novel Role for Corneal Pachymetry in Planning Cataract Surgery by Determining Changes in Spherical Equivalent Resulting from a Previous LASIK Treatment

Objectives. To provide a metric to differentiate between hyperopic and myopic ablation of a prior LASIK treatment based on the corneal pachymetry profile after laser vision correction (LVC). Methods. Pachymetry data were retrospectively recovered from patients who had previous LASIK for refractive purposes between 2019 and 2020. Patients with any corneal disorder were excluded. Ablation spherical equivalent was predicted from the central to semiperipheral corneal thickness (CPT) ratio, both values were provided by using the Pentacam user interface software (UI), and values were computed from extracted raw pachymetry data. Results. Data of 157 eyes of 81 patients were collected, of which data were analysed for 73 eyes of 73 patients to avoid concurrence of measurements in both eyes per subject (42% female; mean age 40.9; SD 12.8). The CPT ratio cutoff for distinction between myopic and hyperopic LASIK was 0.86 for Pentacam UI data. Sensitivity and specificity were 0.7 and 0.95, respectively. Accuracy increased with computation of the CPT ratio based on extracted raw data with sensitivity and specificity of 0.87 and 0.99, respectively. There was a marked linear correlation between the CPT ratio and the ablation spherical equivalent (R2 = 0.93). Conclusions. CPT ratio cutoffs can correctly classify if a cornea previously had a hyperopic versus myopic LASIK surgery and estimate the ablation spherical equivalent of such treatment. This could prove useful for increased accuracy of intraocular lens (IOL) calculations for patients with no historical data of their prior LVC surgery at the time of cataract surgery planning

Description of a patient cohort with Hereditary Sensory Neuropathy Type 1 without retinal disease Macular Telangiectasia type 2 – implications for retinal screening in HSN1

BACKGROUND AND AIMS: Pathogenic variants in the genes encoding serine palmitoyl transferase (SPTLC1 or SPTLC2) are the most common causes of the rare peripheral nerve disorder Hereditary Sensory Neuropathy Type 1 (HSN1). Macular telangiectasia type 2 (MacTel), a retinal disorder associated with disordered serine-glycine metabolism and has been described in some patients with HSN1. This study aims to further investigate this association in a cohort of people with HSN1. METHODS: Fourteen patients with a clinically and genetically confirmed diagnosis of HSN1 from the National Hospital for Neurology and Neurosurgery (NHNN, University College London Hospitals NHS Foundation Trust, London, United Kingdom) were recruited to the MacTel Registry, between July 2018 and April 2019. Two additional patients were identified from the dataset of the international clinical registry study (www.lmri.net). Ocular examination included fundus autofluorescence, blue light and infrared reflectance, macular pigment optical density mapping, and optical coherence tomography. RESULTS: Twelve patients had a pathogenic variant in the SPTLC1 gene, with p.Cys133Trp in eleven cases (92%) and p.Cys133Tyr in one case (8%). Four patients had a variant in the SPTLC2 gene. None of the patients showed clinical evidence of MacTel. INTERPRETATION: The link between HSN1 and MacTel seems more complex than can solely be explained by the genetic variants. An extension of the spectrum of SPTLC1/2-related disease with phenotypic pleiotropy is proposed. HSN1 patients should be screened for visual symptoms and referred for specialist retinal screening, but the association of the two diseases is likely to be variable and remains unexplained. This article is protected by copyright. All rights reserved