Natural history and biomarkers of retinal dystrophy caused by the biallelic TULP1 variant c.148delG

Purpose To report clinical features and potential disease markers of inherited retinal dystrophy (IRD) caused by the biallelic c.148delG variant in the tubby-like protein 1 (TULP1) gene. Methods A retrospective observational study of 16 IRD patients carrying a homozygous pathogenic TULP1 c.148delG variant. Clinical data including fundus spectral-domain optical coherence tomography (SD-OCT) were assessed. A meta-analysis of visual acuity of previously reported other pathogenic TULP1 variants was performed for reference. Results The biallelic TULP1 variant c.148delG was associated with infantile and early childhood onset IRD. Retinal ophthalmoscopy was primarily normal converting to peripheral pigmentary retinopathy and maculopathy characterized by progressive extra-foveal loss of the ellipsoid zone (EZ), the outer plexiform layer (OPL), and the outer nuclear layer (ONL) bands in the SD-OCT images. The horizontal width of the foveal EZ showed significant regression with the best-corrected visual acuity (BCVA) of the eye (p < 0.0001, R-2 = 0.541, F = 26.0), the age of the patient (p < 0.0001, R-2 = 0.433, F = 16.8), and mild correlation with the foveal OPL-ONL thickness (p = 0.014, R-2 = 0.245, F = 7.2). Modelling of the BCVA data suggested a mean annual loss of logMAR 0.027. The level of visual loss was similar to that previously reported in patients carrying other truncating TULP1 variants. Conclusions This study describes the progression of TULP1 IRD suggesting a potential time window for therapeutic interventions. The width of the foveal EZ and the thickness of the foveal OPL-ONL layers could serve as biomarkers of the disease stage.Peer reviewe

Diagnostic assistance system to detect progression of diabetic retinopathy (DR) in fundus images of follow up examinations of patients with diabetes

Abstract Purpose: An important step in detecting and monitoring DR is regular screening by fundus images. The aim is to identify patients with sight-threatening DR timely to be able to initiate adequate treatment and thus to prevent loss of vision (blindness). We developed an algorithm to detect progression between follow up examinations in order to minimize the time consuming diagnostic of the images by an ophthalmologist. Methods: Digital fundus images of 12 patients (4 female, 8 male) with diabetes (10 type 1, 2 type 2) were retrospectively selected from the records of the Department of Ophthalmology of the Oulu University Hospital. Red-free fundus images of each eye were clinically graded for DR, and eyes with progression were included. A 5-step classification was used: no DR, mild DR, moderate DR, severe non-proliferative DR or proliferative DR. There were at least 5 cases presenting every transition, e.g. from no DR to mild DR. A total of 158 grayscale fundus images of 24 eyes were included. The mean age at time of the first examination was 34 ± 15 years, and 43 ± 13 years at the latest examination. The number of examinations varied between 4 and 9 per eye. For each eye, the progression map of all possible combinations of two individual fundus images were calculated. First, the two images were roughly registered with help of a similarity transformation. A finer registration was implemented patchwise together with the adjustment of the contrast between them as a second step. The next step consisted of the calculation of the difference map between the two images. The remaining noise from the background was filtered as a last step by considering the local noise level from the two source images. Results: The transition between the different grades of DR was correctly detected (true positive) in 91% of the instances, and the absence of transition (true negative) in 94%. In 6% of the cases the algorithm signaled progression without clinically detectable change of DR grade (false positive), and in 9% (false negative) the algorithm was not able to detect clinically detected progression. Conclusions: The results demonstrate that the algorithm developed for the detection of progression of DR in fundus images does reliably highlight changes between the images, and has the potential to reduce the time needed for evaluation of images by an ophthalmologist

Low vision rehabilitation over the course of a year:the experiences and feelings of elderly people with visual impairments

Abstract Background/Objective: Low vision rehabilitation (LVR) services aim to help people of all ages with visual impairment (VI) to maintain and improve their quality of life and well-being. However, knowledge about elderly people’s subjective experiences of the usefulness as well as their expectations of LVR is very limited. The aim of this study was therefore to produce new knowledge that can be utilized in the development and improvement of LVR processes and services in order to better support well-being and quality of life, and encourage the ‘active aging’ of elderly people with VI. Methods: Qualitative research methods were used. The data was collected from elderly people with VI (n = 35) by unstructured telephone interviews one year after the onset of individual LVR. The data was analyzed by inductive content analysis. Results: Numerous and varied expectations were expressed for LVR, showing mainly hopes for vision improvement and the need for services and support. The impact of medical care on vision outcome was mentioned in relation to the perceived benefits of LVR. LVR was generally considered useful in terms of overall well-being and quality of life, the main practical benefits being the provision of different visual aids and assistive devices. Conclusions: The results proved the concept, process and multi-sided nature of LVR to be incompletely perceived by the participants in the study. In light of this, we argue that there is a need for improved communication between people with VI and medical staff when discussing the nature and the realistic possibilities of LVR; care should be taken to distinguish it from medical care. The benefits of LVR in enabling independence in daily tasks were commonly recognized, however

Health-related quality of life and related factors among older adults with visual impairments

Abstract Aim was to explore the health-related quality of life (HRQoL) and related factors among older adults with visual impairment (VI). A total of 39 independently living subjects aged ⩾65 years (83 ± 6.5), referred to the Low Vision Center of the Oulu University Hospital, Finland during one year participated in the study. The participants had low vision or blindness as defined by the World Health Organization (WHO). The 15D, a generic HRQoL instrument, was used to assess the HRQoL, and an ophthalmic examination was performed to assess vision. A population-based control group (n = 1074) was available for comparison. The mean 15D index scores for the participants and the control group were 0.768 (SD = 0.089) and 0.827 (SD = 0.044), respectively, (p &lt; 0.002). In the dimensions of move (p &lt; 0.05), see (p &lt; 0.001), breath (p &lt; 0.05), usual activities (p &lt; 0.001), depression (p &lt; 0.05), and distress (p &lt;0 .05), the study participants scored statistically significantly lower than the control group. However, the participants had better mental function scores (0.856 vs 0.773, p &lt; 0.05). Among the participants, there was no difference in the 15D by gender (men 0.755, women 0.774, p > 0.05), habitation (alone 0.768, with someone 0.770, p >0 .05), or age (r = –0.084), nor did the extent of low vision appear to affect the 15D index in this material. The older adults with VI had poorer 15D index score than Finnish population of equal age, but they scored better in the dimension of mental function. Mental skills may indeed be crucial for independent living despite VI

Characteristics of individual low-vision rehabilitation counseling among older adults:a qualitative 2-year follow-up study

Abstract Visual impairments (VI) burden particularly the aging population globally. To ensure healthy aging despite disability, the health care systems must provide effective low-vision rehabilitation services (LVR) for those in need. Low-vision rehabilitation counseling (LVRC) requires specialized multidisciplinary teamwork and has not been studied in detail among the elderly. This study aims to provide a comprehensive picture of individual LVRC actions and introduce a LVRC classification to use for attempts to improve the LVRC processes. This study employed a qualitative follow-up design. Data describing the individual LVRC processes in a prospective cohort of elderly patients with VI (n = 39) were collected individually over 2 years during the years 2016–2019. The data were analyzed through deductive content analysis. The analyzed LVRC provided assistive devices, services, and home modifications, but problems related to independent movement in the living environment, psychosocial burdens, adaptation to disability, and learning new compensatory skills received less attention. To ensure effective LVRC, the multiprofessional team providing the rehabilitation should emphasize goal-setting and continuous assessment. LVRC should be seen as a process of adaptation, adherence, and learning. LVRC should support and promote older adults to participate and function to their full potential in the modern society, which includes utilizing digital technologies

The impact of the image conversion factor and image centration on retinal vessel geometric characteristics

Abstract Background: This study aims to use fundus image material from a long-term retinopathy follow-up study to identify problems created by changing imaging modalities or imaging settings (e.g., image centering, resolution, viewing angle, illumination wavelength). Investigating the relationship of image conversion factor and imaging centering on retinal vessel geometric characteristics (RVGC), offers solutions for longitudinal retinal vessel analysis for data obtained in clinical routine. Methods: Retinal vessel geometric characteristics were analyzed in scanned fundus photographs with Singapore-I-Vessel-Assessment using a constant image conversion factor (ICF) and an individual ICF, applying them to macula centered (MC) and optic disk centered (ODC) images. The ICF is used to convert pixel measurements into μm for vessel diameter measurements and to establish the size of the measuring zone. Calculating a constant ICF, the width of all analyzed optic disks is included, and it is used for all images of a cohort. An individual ICF, in turn, uses the optic disk diameter of the eye analyzed. To investigate agreement, Bland-Altman mean difference was calculated between ODC images analyzed with individual and constant ICF and between MC and ODC images. Results: With constant ICF (n = 104 eyes of 52 patients) the mean central retinal equivalent was 160.9 ± 17.08 μm for arteries (CRAE) and 208.7 ± 14.7.4 μm for veins (CRVE). The individual ICFs resulted in a mean CRAE of 163.3 ± 15.6 μm and a mean CRVE of 219.0 ± 22.3 μm. On Bland–Altman analysis, the individual ICF RVGC are more positive, resulting in a positive mean difference for most investigated parameters. Arteriovenous ratio (p = 0.86), simple tortuosity (p = 0.08), and fractal dimension (p = 0.80) agreed well between MC and ODC images, while the vessel diameters were significantly smaller in MC images (p &lt; 0.002). Conclusion: Scanned images can be analyzed using vessel assessment software. Investigations of individual ICF versus constant ICF point out the asset of utilizing an individual ICF. Image settings (ODC vs. MC) were shown to have good agreement

The natural history of emerging diabetic retinopathy and microalbuminuria from prepuberty to early adulthood in Type 1 diabetes:a 19-year prospective clinical follow-up study

Abstract Objective: To evaluate the impact of long-term glycaemic control and glycaemic variability on microvascular complications in adolescents and young adults with childhood-onset Type 1 diabetes. Methods: Twenty-six participants took part in a prospective follow-up study. We used univariate generalised estimating equations (GEE) analysis with first-order autoregressive AR(1) covariance structure for repeated measurements to evaluate the relationship between emerging diabetic retinopathy (DR) and each single explanatory variable, namely age at developmental stages from late prepuberty until early adulthood, duration of diabetes and long-term HbA1c. Thereafter, the simultaneous effect of these three explanatory variables to DR was analysed in a multivariate model. Results: Twenty-five participants developed DR by early adulthood after a median diabetes duration of 16.2 years (range 6.3–24.0). No participants had DR during prepuberty. Each of the three variables was independently associated with emerging DR: age (OR 1.47, 95% CI to 1.25 to 1.74, p &lt; 0.001) stronger than diabetes duration (OR 1.42, 95% CI 1.23 to 1.63, p &lt; 0.001) and HbA1c (OR 1.02, 95% CI 1.001 to 1.05, p = 0.041) in this population. In the multivariate analysis of these three explanatory variables, only age was associated with DR (adjusted OR 1.52, 95% CI 1.10 to 2.10, p = 0.012). Conclusions: The emergence of DR during adolescence and early adulthood is not rare and increases with age in patients with deteriorating metabolic control during puberty and thereafter. This underpins the need to prevent deterioration of glycaemic control from taking place during puberty—seen again in this follow-up study—in children with diabetes

A novel frameshift variant in CEP78 associated with nonsyndromic retinitis pigmentosa, and a review of CEP78-related phenotypes

Abstract Background: Pathogenic variants in the CEP78 gene can present as atypical Usher syndrome or as retinitis pigmentosa. Here, we present a review of all reported cases of CEP78 variants in the literature to date and present a novel variant of CEP78, c.1261_1262delinsA, in a consanguineous northern Finnish family with two individuals. Materials and methods: Our patients were first discovered in a registry-based study. Later, they gave their written consent for this study. In order to describe the genotype and phenotype, their historic clinical patient data and genetic data were gathered, and a clinical ophthalmic examination and an audiogram were performed. For this review, a PubMed search using the keyword CEP78 was carried out. The first article on CEP78 was published in the year 2007, and the publications from the years 2007–2021 were included. Results: A large gene panel identified a homozygous CEP78 c.1261_1262delinsA variant in two affected siblings. In addition to the classical signs of retinitis pigmentosa, both siblings had large round atrophic spots in the mid periphery, and hyperautofluorescence of the macula. Patient 1 had age-related hearing impairment; patient 2 had normal hearing. In total, 20 articles have been published about CEP78. Eight of these papers report patient data with the affected individuals typically having retinal dystrophy combined with sensorineural hearing impairment, classified as atypical Usher syndrome. Conclusions: Here, we present a comprehensive review of CEP78 and expand the knowledge of pathogenic CEP78 variants and the phenotypic variety

The extent to which mobile applications support independence among the visually impaired:a pilot study

Abstract Background and aim: Visual impairment (VI) problems are increasing as the global aging population grows. Mobile devices have become essential to interacting with friends and society. Because the visually impaired are no exception, it would be useful to determine the functionalities that best support the independence of people with VI. The currently available functionalities and applications were analysed to provide insight about which features the visually impaired value most. Materials and methods: A Webropol survey with structured and open-ended questions was carried out. The participants (n = 26) were asked about their use of mobile applications and opinions regarding the usefulness of certain applications in promoting independent functioning. An instrument was developed for this study based on previous literature, and its quality was assured through an expert panel evaluation and pre-testing. The collected data were analysed statistically and by inductive content analysis. Results: A majority of the participants were active users of mobile devices. Substantial variation was observed in the evaluations of how useful various applications are to different everyday tasks. The participants suggested numerous improvements, such as additional customization, to the current mobile devices and applications. Implications for Rehabilitation: People with VI benefit from the use of mobile devices in the same way that the population with normal vision does, and mobile devices and applications can be pivotal to supporting their independence. The participants offered innovative ideas and suggestions for how mobile devices and applications could be designed to better meet the needs of the visually impaired