A Retrospective Longitudinal Study of 460 Patients with ABCA4-Associated Retinal Disease.

PURPOSE: To investigate the distribution of genotypes and natural history of ABCA4-associated retinal disease in a large cohort of patients seen at a single institution. DESIGN: Retrospective, single-institution cohort review. PARTICIPANTS: Patients seen at the University of Iowa between November 1986 and August 2022 clinically suspected to have disease caused by sequence variations in ABCA4. METHODS: DNA samples from participants were subjected to a tiered testing strategy progressing from allele-specific screening to whole genome sequencing. Charts were reviewed, and clinical data were tabulated. The pathogenic severity of the most common alleles was estimated by studying groups of patients who shared 1 allele. Groups of patients with shared genotypes were reviewed for evidence of modifying factor effects. MAIN OUTCOME MEASURES: Age at first uncorrectable vision loss, best-corrected visual acuity, and the area of the I2e isopter of the Goldmann visual field. RESULTS: A total of 460 patients from 390 families demonstrated convincing clinical features of ABCA4-associated retinal disease. Complete genotypes were identified in 399 patients, and partial genotypes were identified in 61. The median age at first vision loss was 16 years (range, 4-76 years). Two hundred sixty-five families (68%) harbored a unique genotype, and no more than 10 patients shared any single genotype. Review of the patients with shared genotypes revealed evidence of modifying factors that in several cases resulted in a > 15-year difference in age at first vision loss. Two hundred forty-one different alleles were identified among the members of this cohort, and 161 of these (67%) were found in only a single individual. CONCLUSIONS: ABCA4-associated retinal disease ranges from a very severe photoreceptor disease with an onset before 5 years of age to a late-onset retinal pigment epithelium-based condition resembling pattern dystrophy. Modifying factors frequently impact the ABCA4 disease phenotype to a degree that is similar in magnitude to the detectable ABCA4 alleles themselves. It is likely that most patients in any cohort will harbor a unique genotype. The latter observations taken together suggest that patients' clinical findings in most cases will be more useful for predicting their clinical course than their genotype. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Auditory Global Positioning System and Advanced Driver Assistance Systems: A Safer Alternative to Bioptic Telescopes for Drivers Who Are Visually Impaired?

This work challenges the standard of the past 40 years, which required the use of a bioptic telescope by individuals with vision loss wanting to be licensed to drive in most states in the United States.Driving continues to be the key to independence for many individuals, particularly older drivers who live in an area where public transportation is limited or nonexistent. For the past 40 years, the most frequently option to allow drivers who are visually impaired to maintain driving privileges was to require them to use a bioptic telescope. Bioptic telescopes were felt to be necessary for wayfinding when driving. In addition, it was thought that a person could look through a bioptic telescope and still be aware of the driving environment around him/her. Human factor research has shown that the assertion that an individual can attend to two tasks simultaneously is not possible. Taking one's eyes off the road for as little as 2 seconds can lead to lane position breakdown. In 2018, wayfinding can now be more easily accomplished with the use of ubiquitous technologies like Global Positioning System systems on our telephones and in our cars. Driver distraction principles support safer alternatives to bioptic telescopes because these audio options allow the drivers to maintain their eyes and their attention on the road and the traffic around them. The switching of view within the bioptic spectacles is attentionally demanding, and the visual field restriction of such devices reduces overall situation awareness by narrowing the driver's attention.

Peroxisome biogenesis disorders in the Zellweger spectrum: An overview of current diagnosis, clinical manifestations, and treatment guidelines.

Peroxisome biogenesis disorders in the Zellweger spectrum (PBD-ZSD) are a heterogeneous group of genetic disorders caused by mutations in PEX genes responsible for normal peroxisome assembly and functions. As a result of impaired peroxisomal activities, individuals with PBD-ZSD can manifest a complex spectrum of clinical phenotypes that typically result in shortened life spans. The extreme variability in disease manifestation ranging from onset of profound neurologic symptoms in newborns to progressive degenerative disease in adults presents practical challenges in disease diagnosis and medical management. Recent advances in biochemical methods for newborn screening and genetic testing have provided unprecedented opportunities for identifying patients at the earliest possible time and defining the molecular bases for their diseases. Here, we provide an overview of current clinical approaches for the diagnosis of PBD-ZSD and provide broad guidelines for the treatment of disease in its wide variety of forms. Although we anticipate future progress in the development of more effective targeted interventions, the current guidelines are meant to provide a starting point for the management of these complex conditions in the context of personalized health care.

Long-term daily stream temperature record for Scotland reveals spatio-temporal patterns in warming of rivers in the past and further warming in the future.

Stream temperature is directly and indirectly affected by climate change. To be able to project future changes in stream temperature, historic trends and factors influencing these trends need to be understood. There is a demand for daily data to analyse historical trends and future changes in stream temperature. However, long-term daily stream temperature data are rare and observations of coarse temporal resolution (e.g. once-a-month) do not allow for robust trend analyses. Here, we present a methodology to reconstruct a national long-term daily stream temperature record (1960-2080) from 40 years of once-a-month observations (for 45 Scottish catchments). This involved implementing climatic and hydrological variables in generalized additive models. These models were then used in combination with regional climate projections (UKCP18 Strand 3 - RCP8.5) to predict future spatio-temporal temperature patterns. The results indicate that for the Scottish dataset (i) in addition to air temperature, the dominant environmental controls on stream temperature are unique combinations for each catchment; (ii) a general increase of up to 0.06 °C/year in historic stream temperature over all catchments resulted mainly from increases in spring and summer stream temperatures; (iii) future spatial patterns in stream temperature are more homogenous and differ therefore from the past where temperatures in N Scotland were relatively lower; (iv) future changes of up to +4.0 °C in annual stream temperature are strongest in those catchments which show lower stream temperature in the past (NW and W Scotland). These results are important in the context of water quality and stream temperature management. The methodology can be applied to smaller scale sites or to other national/global datasets enabling the analysis of historic trends and future changes at a high temporal resolution.

Predominance of hyperopia in autosomal dominant Best vitelliform macular dystrophy.

BACKGROUND/AIMS: Patients with BEST1-associated autosomal dominant Best vitelliform macular dystrophy (AD-BVMD) have been reported to be hyperopic, but the prevalence of refractive error has not been described. This study aimed to characterise the type and degree of refractive error in a large cohort of patients with AD-BVMD compared with an age-similar group with ABCA4-associated Stargardt disease. METHODS: This was a retrospective chart review of consecutive patients with molecularly confirmed AD-BVMD and Stargardt macular dystrophy seen at a single academic centre. Demographic information, including age, gender and genotype were extracted from the chart. The best corrected visual acuity (BCVA), as well as type and degree of refractive error on manifest refraction for each eye on each visit, were recorded and compared. RESULTS: A total of 178 eyes from 89 patients with AD-BVMD (35 women, 54 men; mean age 36.6 years) and 306 eyes from 153 patients (94 women, 59 men, mean age 30.2 years) with Stargardt disease were included in the study. Mean BCVA was excellent for both AD-BVMD and Stargardt eyes (logMAR 0.23 vs logMAR 0.31, respectively; p=0.55). At initial refraction, 73.0% of AD-BVMD eyes (130/178) were hyperopic, with mean spherical equivalent (SE) +1.38 dioptres (median +0.88) whereas 80.7% of Stargardt eyes (247/306) were myopic, with mean SE of -1.76 dioptres (median -1.19) (p<0.001). CONCLUSION: Patients with AD-BVMD are predominantly hyperopic, whereas those with Stargardt disease are predominantly myopic. The findings provide further evidence of a role for BEST1 in ocular growth and development.

Embankment lowering and natural self-recovery improves river-floodplain hydro-geomorphic connectivity of a gravel bed river.

Floodplain reconnection can potentially improve the hydrogeomorphology of river corridors and attenuate flood peaks. However, empirical evidence of its effectiveness - needed to inform future restoration - is limited. A 70 m long flood embankment was lowered on the upper River Dee, a medium sized gravel bed river in north-east Scotland to reconnect a backwater and floodplain. Comparison of two years pre- and three years of post-restoration hydro-geomorphic monitoring, shows the lowering and subsequent adjustment, assisted by several floods including a <1% annual exceedance probability event, have altered the morphology and hydrological dynamics. Channel aggradation of up to 1 m occurred. Erosion of the bank by up to 0.41 m in depth and deposition of gravel or sand within the backwater and the floodplain were the dominant geomorphic responses elsewhere. The channel adjustment, unexpected in the restoration design, improved hydrological connectivity with the floodplain; annual median water table levels were on average 0.037-0.089 m higher post-restoration although the correlation between river discharge and floodplain water levels did not change. Based on 1D modelling, the threshold river discharge for backwater connection decreased by 55% from 93 m3 s-1 (discharge exceedance percentile: Q0.4) to 42 m3 s-1 (Q8). Thus, overspill frequency increased. For a given peak discharge, floodplain water levels were higher on average by 0.25 m with a statistically significant difference (Mann Whitney U test: p < 0.05), due to improved hydrological connectivity. The monitoring demonstrates that localised but significant improvement of channel to floodplain hydro-geomorphic connectivity can result from targeted embankment lowering. Such actions could enhance future catchment resilience by improving water storage and biogeochemical processing.

Vision and driving in multiple sclerosis.

OBJECTIVE: To examine the relationship between measures of visual dysfunction and driving performance in persons with multiple sclerosis (MS). DESIGN: Between-group comparison. SETTING: All data were collected in an outpatient research setting. PARTICIPANTS: Persons (N=66) with MS of the relapsing remitting type (26 self-reporting visual difficulties; 40 self-reporting no visual difficulties) and 26 age- and sex-matched healthy controls. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Measures of vision included visual acuity, depth perception, and color perception. Driving was measured using documented accident/violation rate and self-reported driving behaviors. RESULTS: Quantitative analysis only revealed that MS persons with self-reported visual difficulties performed significantly worse than healthy controls on color perception (Kruskal-Wallis; chi(2)(2)=8.89, P=.01). There were no group differences on driving behaviors, and correlational analysis revealed a lack of relationship between the selected visual (visual acuity, depth perception, color perception) and driving performance measures (documented accident/violation rate and self-limiting driving behaviors). CONCLUSIONS: Persons with MS who self-reported difficulties with vision had acceptable visual acuity, despite demonstrating impairment in color perception. The fact that visual acuity remains the most common measure for visual fitness to drive remains problematic. There is a need to further define measures of visual dysfunction relevant to driving among this clinical population.

Vision and driving: the United States.

Minimal visual standards for obtaining driving licensure in the United States principally use 2 measures: visual acuity and visual field. Although research studies have established a correlation between performance on these measures and safe driving, the correlations are weak and mostly retrospective. These measures remain in place in screening centers largely because they (especially visual acuity) are practical. A newer test of visual attention, called the useful field of view, may be more predictive of safe driving than the traditional measures, but it has not been widely applied in licensing bureaus.

Evaluation and management consideration for children who are visually impaired.

Clinical low vision evaluations provided by optometrists or ophthalmologists trained and experienced in low vision rehabilitation care should be recommended for all children with a visual impairment, regardless of the cause of their vision loss, their age or the severity of their additional disabilities. This article discusses an effective model for pediatric vision rehabilitation service.

Attaining functional levels of visual acuity after vitrectomy for retinal detachment secondary to proliferative diabetic retinopathy.

Most patients needing diabetic tractional retinal detachment (TRD) surgery are working-age adults that drive and participate in other vision-dependent activities of daily living. We sought to determine the proportion of patients that achieve functional visual acuity (VA) based on the World Health Organization (WHO) definition of 'low vision' (≤ 20/80) and US driving standards (≥ 20/40) after vitrectomy for diabetic TRD. In this 10-year retrospective review, consecutive patients who underwent primary vitrectomy for TRD from proliferative diabetic retinopathy were studied. 240 eyes in 203 patients met criteria for analysis (38 eyes were lost to follow up at 3 months; 68 at 12 months; 146 at 60 months). While most patients (nearly 80%) having TRD surgery had low vision pre-op, almost half attained VA that was > 20/80 five years post-op. Those most likely to achieve significant visual improvement (p < 0.0001) had concomitant vitreous hemorrhage pre-op. Only 6% of eyes met the US minimum driving standard before surgery based on VA compared to 28% after vitrectomy however this study did not examine visual fields which could warrant additional assessment depending on local requirements. In summary, significant gains in visual acuity are seen after vitrectomy for diabetic TRD that can result in functional improvement in activities of daily living.

Integration of juvenile habitat quality and river connectivity models to understand and prioritise the management of barriers for Atlantic salmon populations across spatial scales.

Diadromous fish populations are strongly affected by in-stream barriers that cause river network fragmentation, constraining productivity or preventing completion of their lifecycle. Removal or reduction of barrier impacts is a restoration measure associated with unambiguous benefits. Management of barriers is therefore often prioritised above other restoration actions. Barrier management is prioritised at local and national scales depending on funding. However, barrier prioritisation is potentially sub-optimal because existing tools do not consider habitat quality. Furthermore, effects of partial barriers (those passable under certain conditions) are uncertain, depending on location and potential cumulative effects. A framework is presented for assessing effects of impassable manmade barriers (IMBs) on longitudinal river network connectivity (percentage of upstream habitat accessible from the river mouth) for Atlantic salmon across spatial scales, using Scotland as an example. The framework integrates juvenile habitat quality and network connectivity models to (1) provide information necessary for local and national prioritisation of barriers, and (2) assess potential effects of passable manmade barriers (PMBs) within a sensitivity framework. If only IMBs are considered, high levels of longitudinal connectivity are observed across most of Scotland's rivers. Barrier prioritisation is sensitive to habitat weighting: not accounting for habitat quality can lead to over- or underestimating the importance of IMBs. Prioritisation is also highly sensitive to the passability of PMBs: if passability drops to <97% (combined up- and downstream passability), the mean effect of PMBs becomes greater than IMBs at the national level. Moreover, impacts on catchment connectivity, and thus production (number of juvenile salmon produced by the river), could be severe, suggesting a better understanding of the passability of PMBs is important for future management of migration barriers. The presented framework can be transferred to other catchments, regions, or countries where necessary data are available, making it a valuable tool to the broader restoration community.

Structure from motion photogrammetry in ecology: Does the choice of software matter?

Image-based modeling, and more precisely, Structure from Motion (SfM) and Multi-View Stereo (MVS), is emerging as a flexible, self-service, remote sensing tool for generating fine-grained digital surface models (DSMs) in the Earth sciences and ecology. However, drone-based SfM + MVS applications have developed at a rapid pace over the past decade and there are now many software options available for data processing. Consequently, understanding of reproducibility issues caused by variations in software choice and their influence on data quality is relatively poorly understood. This understanding is crucial for the development of SfM + MVS if it is to fulfill a role as a new quantitative remote sensing tool to inform management frameworks and species conservation schemes. To address this knowledge gap, a lightweight multirotor drone carrying a Ricoh GR II consumer-grade camera was used to capture replicate, centimeter-resolution image datasets of a temperate, intensively managed grassland ecosystem. These data allowed the exploration of method reproducibility and the impact of SfM + MVS software choice on derived vegetation canopy height measurement accuracy. The quality of DSM height measurements derived from four different, yet widely used SfM-MVS software-Photoscan, Pix4D, 3DFlow Zephyr, and MICMAC, was compared with in situ data captured on the same day as image capture. We used both traditional agronomic techniques for measuring sward height, and a high accuracy and precision differential GPS survey to generate independent measurements of the underlying ground surface elevation. Using the same replicate image dataset (n = 3) as input, we demonstrate that there are 1.7, 2.0, and 2.5 cm differences in RMSE (excluding one outlier) between the outputs from different SfM + MVS software using High, Medium, and Low quality settings, respectively. Furthermore, we show that there can be a significant difference, although of small overall magnitude between replicate image datasets (n = 3) processed using the same SfM + MVS software, following the same workflow, with a variance in RMSE of up to 1.3, 1.5, and 2.7 cm (excluding one outlier) for "High," "Medium," and "Low" quality settings, respectively. We conclude that SfM + MVS software choice does matter, although the differences between products processed using "High" and "Medium" quality settings are of small overall magnitude.

Low vision rehabilitation: An update.

This article provides information concerning issues related to the care of individuals who are visually impaired. Issues reviewed include determining who should be referred for vision rehabilitation services, Charles Bonnet syndrome, visual acuity, contrast sensitivity and visual field testing along with Useful Field of View testing. This article also discusses technology advances that can enhance the visual functioning of individuals who are visually impaired, including how these advances can help drivers with visual impairments to continue to safely operate motor vehicles, at least on a limited basis. Finally, resources that are available to both encourage and motivate patients to take advantages of vision rehabilitation services are reviewed.

The science, policy and practice of nature-based solutions: An interdisciplinary perspective.

In this paper, we reflect on the implications for science, policy and practice of the recently introduced concept of Nature-Based Solutions (NBS), with a focus on the European context. First, we analyse NBS in relation to similar concepts, and reflect on its relationship to sustainability as an overarching framework. From this, we derive a set of questions to be addressed and propose a general framework for how these might be addressed in NBS projects by funders, researchers, policy-makers and practitioners. We conclude that: To realise their full potential, NBS must be developed by including the experience of all relevant stakeholders such that 'solutions' contribute to achieving all dimensions of sustainability. As NBS are developed, we must also moderate the expectations placed on them since the precedent provided by other initiatives whose aim was to manage nature sustainably demonstrates that we should not expect NBS to be cheap and easy, at least not in the short-term.

Low vision rehabilitation: a concise overview.

This article provides a concise overview of low vision, evaluation and rehabilitation.