Visual Decline Research Articles

Unexplained visual loss after primary pars-plana-vitrectomy with silicone oil tamponade in fovea-sparing retinal detachment

BackgroundTo investigate the incidence and clinical characteristics of unexplained visual loss in patients with fovea-sparing rhegmatogenous retinal detachment (RRD) during or after silicone oil (SO) tamponade.MethodsThe medical charts of all patients with macula-on RRDs, who underwent pars-plana-vitrectomy (ppV) with SO tamponade were retrospectively assessed regarding unexplained visual loss (UVL) of ≥ 3 Snellen lines and alterations on optical coherence tomography (OCT) during or after SO tamponade. The clinical data analysed included visual acuity, surgical parameters, OCT images, duration of SO tamponade and the time point of visual decline. Cases with re-detachment or secondary causes of visual loss such as SO emulsification, epiretinal membranes or macular edema were excluded.ResultsOver a 15-year-period, 22 cases with macula-on RRD, which had primarily been treated with ppV and SO tamponade, met the inclusion criteria. In most eyes (n = 20; 91%), the RRD was caused by a giant retinal tear (GRT). In 11 of these 22 cases (50%), best-corrected visual acuity (BCVA) had dropped by at least 3 lines for no apparent reason. In these 11 cases, mean preoperative logMAR BCVA was 0.2 (SD 0.13; range 0-0.5), equal to Snellen’s VA of 0.63, and mean postoperative logMAR BCVA 1.0 (SD 0.24; range 0.5–1.3), equal to Snellen’s VA of 0.10. Visual decline occurred about 12 weeks postoperatively (SD 6.2; range 3–20 ) and comprised 8 lines (SD 2.3; range -11 to -4). SO was removed on average 139 (SD 50.0; range 88–271) days after the first ppV. In 9 cases visual decline occurred while the SO was in-situ. In 2 patients, BCVA decline was noted 2 weeks after SO removal. In all eyes, preoperative central foveal thickness (CFT) was 254 μm (SD 24.2), which decreased to 224 μm (SD 29.6) during SO tamponade and increased to 247 μm (SD 29.2) after SO removal, irrespective of the presence of UVL. The mean follow-up time was 20 months (SD 30.6) after SO removal.ConclusionUVL after SO tamponade for macula-on RRD is more frequent than expected. The incidence in our case series was 50%. The mechanism of this phenomenon is still unknown. In general, vitreoretinal surgeons should thoroughly question the need for SO tamponade, inform their patients of possible UVL and remove SO as early as possible.Trial registrationThe study was approved by the local ethics committee on 6th of May 2022 (Ethikkommission der Universität Regensburg, Votum 22-2925-104) and was conducted in accordance with the ethical standards of the Declaration of Helsinki.

Postoperative Echography for Optimization of Radiation Dosimetry in Patients with Uveal Melanoma Treated with Plaque Brachytherapy

1) To describe the technique of post-operative echography to confirm the intended treatment dose to the tumor apex in patients with uveal melanoma treated with plaque brachytherapy, 2) To describe the local tumor control rate and visual outcomes with the brachytherapy strategies used at our institution. Retrospective review SUBJECTS: 372 consecutive patients with uveal melanoma (small, medium, and large) treated with plaque brachytherapy at the University of Iowa from 8/2008-2/2019. Patient demographics and tumor characteristics were recorded for each patient. Patients with posterior tumors treated with plaque brachytherapy (n=355) underwent intra-operative ultrasound to confirm plaque placement, and additional post-operative ultrasound on day 1-3 post plaque insertion. In cases where intra-tumor/episcleral plaque edema or hemorrhage shifted the dose to the prescription point to less than 85 Gray (Gy), the duration of plaque brachytherapy was increased to compensate. Statistical analysis was performed to compare variables associated with need for plaque adjustment. Variables associated with plaque dose needing to be re-calculated, local tumor control, and visual acuity outcomes. In 31 cases (8.3%), post-operative echography showed the tumor apex had shifted outside of the 85 Gy isodose curve, requiring adjustment of the duration of brachytherapy (28 cases) or repositioning of the plaque (3 cases). Collaborative Ocular Melanoma Study (COMS) tumor size was significantly associated with need to adjust the plaque prescription dose (p=0.03), with large tumors having the highest rate of adjustment. Tumor thickness was larger in cases requiring plaque adjustment compared to those that were not adjusted (median 4.9 mm versus 3.0 mm, p<0.01). Local tumor control was 99% (95% CI: 97-100%) at 5 years and 99% (95% CI: 97-100%) at 10 years. The percentage of patients who had experienced a visual acuity decline of ≥3 lines of vision or had less than 20/200 acuity was 14.9% at one year post brachytherapy, 35.3% at three years, and 51.6% at five years. Post-operative ultrasound performed on post-operative day 1-3 after plaque insertion for patients undergoing brachytherapy for uveal melanoma may result in improved local tumor control, particularly in the setting of thicker or larger tumors.

Retinitis Pigmentosa: Novel Therapeutic Targets and Drug Development.

Retinitis pigmentosa (RP) is a heterogeneous group of hereditary diseases characterized by progressive degeneration of retinal photoreceptors leading to progressive visual decline. It is the most common type of inherited retinal dystrophy and has a high burden on both patients and society. This condition causes gradual loss of vision, with its typical manifestations including nyctalopia, concentric visual field loss, and ultimately bilateral central vision loss. It is one of the leading causes of visual disability and blindness in people under 60 years old and affects over 1.5 million people worldwide. There is currently no curative treatment for people with RP, and only a small group of patients with confirmed RPE65 mutations are eligible to receive the only gene therapy on the market: voretigene neparvovec. The current therapeutic armamentarium is limited to retinoids, vitamin A supplements, protection from sunlight, visual aids, and medical and surgical interventions to treat ophthalmic comorbidities, which only aim to slow down the progression of the disease. Considering such a limited therapeutic landscape, there is an urgent need for developing new and individualized therapeutic modalities targeting retinal degeneration. Although the heterogeneity of gene mutations involved in RP makes its target treatment development difficult, recent fundamental studies showed promising progress in elucidation of the photoreceptor degeneration mechanism. The discovery of novel molecule therapeutics that can selectively target specific receptors or specific pathways will serve as a solid foundation for advanced drug development. This article is a review of recent progress in novel treatment of RP focusing on preclinical stage fundamental research on molecular targets, which will serve as a starting point for advanced drug development. We will review the alterations in the molecular pathways involved in the development of RP, mainly those regarding endoplasmic reticulum (ER) stress and apoptotic pathways, maintenance of the redox balance, and genomic stability. We will then discuss the therapeutic approaches under development, such as gene and cell therapy, as well as the recent literature identifying novel potential drug targets for RP.

A visually guided swim assay for mouse models of human retinal disease recapitulates the multi-luminance mobility test in humans.

The purpose of this study was to develop a visually guided swim assay (VGSA) for measuring vision in mouse retinal disease models comparable to the multi-luminance mobility test (MLMT) utilized in human clinical trials. Three mouse retinal disease models were studied: Bardet-Biedl syndrome type 1 (Bbs1M390R/M390R), n = 5; Bardet-Biedl syndrome type 10 (Bbs10-/-), n = 11; and X linked retinoschisis (retinoschisin knockout; Rs1-KO), n = 5. Controls were normally-sighted mice, n = 10. Eyeless Pax6Sey-Dey mice, n = 4, were used to determine the performance of animals without vision in VGSA. Eyeless Pax6Sey-Dey mice had a VGSA time-to-platform (TTP) 7X longer than normally-sighted controls (P < 0.0001). Controls demonstrated no difference in their TTP in both lighting conditions; the same was true for Pax6Sey-Dey. At 4-6 M, Rs1-KO and Bbs10-/- had longer TTP in the dark than controls (P = 0.0156 and P = 1.23 × 10-8, respectively). At 9-11 M, both BBS models had longer TTP than controls in light and dark with times similar to Pax6Sey-Dey (P < 0.0001), demonstrating progressive vision loss in BBS models, but not in controls nor in Rs1-KO. At 1 M, Bbs10-/- ERG light-adapted (cone) amplitudes were nonrecordable, resulting in a floor effect. VGSA did not reach a floor until 9-11 M. ERG combined rod/cone b-wave amplitudes were nonrecordable in all three mutant groups at 9-11 M, but VGSA still showed differences in visual function. ERG values correlate non-linearly with VGSA, and VGSA measured the continual decline of vision. ERG is no longer a useful endpoint once the nonrecordable level is reached. VGSA differentiates between different levels of vision, different ages, and different disease models even after ERG is nonrecordable, similar to the MLMT in humans.

Retinal Neurodegeneration and Visual Acuity Decline in Patients with Chronic Kidney Disease.

Chronic kidney disease (CKD) has been associated with accelerated retinal neurodegeneration. The purpose of this study is to evaluate the association between retinal neurodegeneration and the best-corrected visual acuity (BCVA) decline in patients with CKD. Post hoc analysis of two prospective studies. Patients with CKD stage≥3 were enrolled. Macular thickness, peripapillary retinal nerve fiber layer (pRNFL) thickness, and macular ganglion cell complex (GCC) thickness were measured by optical coherence tomography. Eyes were classified into three groups: Group 1, no GCC defect; Group 2, GCC defect confined to parafoveal area; and Group 3, GCC defects extending beyond the parafoveal area. Each group was matched for age, sex, axial length, lens status, and cataract grading. A total of 120 eyes (40 eyes in each group) from 120 patients (age 63.0±10.3years) were included. The logMAR BCVA was 0.076±0.101, 0.100±0.127, and 0.196±0.191 in Group 1, 2, and 3, respectively. Group 3, but not Group 2, had a significantly worse BCVA than Group 1. In simple linear regression, parafoveal inner retinal thickness, pRNFL thickness, presence of pRNFL defect, GCC thickness, GCC global loss volume, GCC focal loss volume, and GCC defect extending beyond parafoveal area were associated with BCVA. Central subfield retinal thickness (CRT), parafoveal full retinal thickness, and parafoveal outer retinal thickness were not associated with BCVA. In backward stepwise linear regression, age and GCC defects extending beyond the parafoveal area were factors associated with BCVA. Moreover, GCC defect extending beyond parafoveal area was connected with worse BCVA in both phakic and pseudophakic subgroups. GCC defect extending beyond parafoveal area could be an independent biomarker associated with decreased BCVA in patients with CKD. However, macular thinning measured by CRT or parafoveal full retinal thickness might have low discriminative power in determining BCVA.

VISUAL IMPAIRMENT PREDICTS PHYSICAL FUNCTION DECLINE: THE HEALTH, AGING, AND BODY COMPOSITION (HEALTH ABC) STUDY

Abstract The relationship between visual impairment (VI) and decline in physical function with age is poorly understood. We constructed separate linear mixed models to evaluate the relationship of self-reported (visual function question (VFQ) score) or performance-based (visual acuity (VA); log contrast sensitivity (LCS); stereoacuity (SA)) VI with change in performance on the Short Physical Performance Battery (SPPB) over 8 years in 2219 Health ABC participants. Mean age was 75.5 years (range 71-82); 52.4% were female, and 37.4% were black. For all measures of visual function, better vision was associated with loss of approximately -0.3 SPPB units/year which was similar to the unadjusted change in SPPB over time (-0.328 units/year 95%CI (-0.35, -0.31)). Participants with LCS ≤1.3 log units experienced 58% faster rate of decline versus those with better LCS (test of difference in slopes p&amp;lt; 0.0001). Those with poor VA ≥20/50 showed a 50% greater decline in SPPB (p=0.0029), and those with low SA ≤85 arcsec demonstrated a 33% faster decline (p&amp;lt; 0.001) relative to those with better visual function. Compared to the slope at the mean VFQ score, a 1 standard deviation lower score was associated with 23% greater decline in SPPB (p&amp;lt; 0.0001). The difference in SPPB slopes remained significant across VI measures after adjusting for longitudinal decline associated with age, sex, and black race (all p&amp;lt; 0.05). Both self-reported and performance-based VI predicted faster declines in SPPB over time. Whether older adults with VI might benefit from targeted intervention to prevent declining mobility function remains to be evaluated.

Usefulness of critical flicker fusion frequency measurement and its laterality for evaluating compressive optic neuropathy due to pituitary neuroendocrine tumors.

Critical flicker fusion frequency (CFF) is a short but sensitive method for evaluating optic nerve function. We measured CFF in patients with pituitary neuroendocrine tumors (Pit-NETs) to assess its usefulness. Data from 184 patients with nonfunctioning Pit-NETs, who had been treated with transsphenoidal surgery and had no medical history of eye diseases, was used in this retrospective study. Visual acuity decline (VAD) was defined as > 0.10 reduction in logMAR visual acuity and CFF decline (CFD) was defined as CFF value < 35Hz. Visual field defect (VFD) was evaluated by automated perimetry on a Humphrey visual field analyzer. Potential associations between abnormal test results and tumor height from the suprasellar were analyzed. Contact between the optic nerve or chiasma and the tumor was present and absent in 161 and 23 patients, respectively. In patients showing contact, the difference in CFF between the left and right eyes was larger (p = 0.0008), and the optimal cutoff value using the receiver operating characteristic curve was 3Hz. Therefore, ≥ 3Hz was considered positive for CFF laterality (CFL), the most prevalent condition. Tumor height was lower in patients with CFL positivity compared to those with VAD or VFD (p < 0.01). The prevalence of test abnormalities was the highest for small tumors compared to those of other tests. Changes in CFL permit early detection of Pit-NETs. Our results indicate that CFF laterality can be seen in the early stages of compressive optic neuropathy due to Pit-NET.

Is the retinal senescent due to neuronal disfunction or neuronal death?

AbstractThe continuous decline in vision due to aging is a common and irreversible degenerative process that is a consequence of multiple cumulative factors. Genetic heritage, behaviour, nutrition, and environmental factors are tangled along the course of life making aging a heterogeneously complex process. This contributes to make the inherent effects of aging difficult to evaluate in vision, and more so, when its outcome is often masked by other chronic ocular pathologies.Thus, investigating small mammals (rodents) under controlled conditions (food, environmental light, and temperature), we characterized the functional and anatomical changes in the aged retina. Full field electroretinograms in aged rodents displayed retinal function reduced by ~50% of the averaged response observed in juvenile ones. However, we did not observe any corneal or lens opacification that could provide any functional deficit. Therefore, based on the literature, we investigated whether neuronal loss in any of the different retinal layers could explain the reduced functionality. First, we estimated neuronal loss by examining the retinal thickness in vivo by Optical Coherence Tomography. As reported for aged mice and rats, we also observed a significant retinal thinning (&lt;20%) as measured by the total retinal thickness. However, this retinal thinning could not completely account for the ~50% reduction in retinal function.Consequently, we focused on the anatomical changes on aged retinas by quantifying two key neurons in the visual pathway: the photoreceptors, responsible for light capture, and the retinal ganglion cells (RGC), unique afferent neurons in the retina that project to the brain. First, Immunohistochemical analysis corroborated the retinal thinning; and second, quantitative analysis of Opsin and Brn3a (markers for photoreceptors and RGC respectively) demonstrated reduced densities in both cell populations as reported in other mammals. Interestingly, we found photoreceptor degeneration in the central retina of aged rodents. However, total quantification of RGCs in aged animals showed no significant differences compared to juvenile ones. By taking into account the growth of the retina over the lifetime of the rodents, the difference in retinal area provided an explanation to the observed retinal thinning and reduced RGC density across the retinal surface since volumetric analysis did not provide clear evidence of neuronal loss.Next, we assessed the glial state on aged brain and retina samples. In aged tissues, the microglial cells (Iba1) had ramified morphology, but quantitative analysis revealed a significant reduced dendritic arbor. Expression of GFAP in astrocytes and CD68, a lysosomal protein expressed on active phagocytic cells, showed a significant increase during healthy aging. Features that may contribute to a chronic parainflammation.Overall, these and previous data suggest that the reduced retinal function caused by aging may derive from neuronal disfunction, photoreceptor degeneration and imbalance of immune processes, including alterations in inflammation. Thus, the importance to better understanding of the aging processes become more crucial than ever before since our livespan is increasing over the years. Therefore, an early detection of these symptoms may help to identify healthier lifestyles to prevent vision loss, or to design new potential treatments to preserve or to restore vision.

Mystery of changing choroidal thickness.

Mystery of changing choroidal thickness.

A systematic literature review of disease progression in RPGR‐associated X‐linked retinitis pigmentosa

AbstractPurpose: To assess disease progression qualitatively and quantitatively in RPGR‐associated X‐linked retinitis pigmentosa (RPGR‐XLRP).Methods: PubMed was used to identify relevant studies (01/2000–09/2021). Search terms included RP, XLRP, history, progress, disease state, health state, and burden. Included studies focused on RPGR‐XLRP (ie, results specific to RPGR or RP studies with ≥80% of patients with RPGR variants). Endpoints of interest included changes in visual acuity (VA), visual field (VF), and ellipsoid zone width (EZW), progression to legal blindness, and patient‐reported outcomes (PROs).Results: Of 1325 studies captured by search criteria (including those examining XLRP [n = 17], RP [127], and both XLRP and RP [6]), 11 met inclusion criteria for assessment of RPGR‐XLRP disease progression. In those with RPGR‐XLRP, data suggest progressive decline in VA, VF, and EZW. Annual changes in VA were equivocal, with two studies reporting positive or minimal change in best‐corrected VA (BCVA; +2%, −0.07%) and two studies reporting VA decline (−3.5 to −5.3%, −8.2%). Annual declines in VF, measured via Goldmann or Humphrey perimetry, were observed across studies (range, −4.5, −9.0%; n = 4 studies). EZW, measured via Heidelberg Spectralis OCT, became constricted over time (n = 5 studies); 2 studies showed an 8%–9% annual exponential rate of decline. In two studies, patients reached VA‐based legal blindness (BCVA &lt;20/400 in the better seeing eye or &lt;6/60) by median ages of 48 and 51.3 years; in another study, 18% reached blindness (BCVA &lt;20/400) by age 40. PRO data in this patient population were limited.Conclusions: Published evidence shows that those with RPGR‐XLRP experience significant progressive decline in VA, VF, and EZW, eventually resulting in blindness. There is a need for more standardized longitudinal data and expanded collection of PROs to better assess visual decline in RPGR‐XLRP.

The fast‐aging killifish: A unique vertebrate model to identify molecular targets for neuroreparative strategies in the aged retina

AbstractThe rise in life expectancy in our modern societies concurs with an increasing prevalence of age‐associated neurodegenerative disorders and central nervous system (CNS) trauma. Despite many research attempts trying to unravel aging processes and their role in functional decline, the mechanisms underlying healthy CNS aging remain elusive. Moreover, the reparative approaches proposed to combat loss of neurons due to damage or (age‐associated) disease are failing. One of the reasons might be that the currently used animal models often lack the capability to properly recapitulate the aged environment in which these pathologies manifest and the repair processes need to occur. We introduce the African turquoise killifish as an opportune model to study CNS aging as well as neuroreparative strategies. Indeed, while sharing adult neuroregenerative potential with other teleost fish like zebrafish, the short‐lived killifish displays many of the human aging hallmarks, making it a promising biogerontology model.As vision decline manifests during human aging and in many neurodegenerative diseases, we performed a comprehensive characterization of the aged killifish visual system, comprising the retina, optic projections and optic tectum. Immunohistochemical, biochemical and molecular analyses revealed the presence of many aging traits in this system, including oxidative stress, genomic damage, cellular senescence, altered cellular communication, reduced neurogenic potential and even neurodegeneration. Specifically, microglia changed to a pro‐inflammatory secretion profile upon aging and macroglia became gliotic in the aging killifish visual system. Altogether, these age‐related changes led to a diminished visual performance in old killifish.Using an optic nerve injury model, we further disclosed an age‐related decline in functional circuit restoration, with different phases of the repair process being affected depending on the age. While young adult killifish were able to functionally recover after injury, old fish did not regain vision at all. Here we observed for the first time in a regenerative teleost fish model, a glial scar that formed a mechanical barrier physically preventing axonal regrowth. Moreover, in the optic tectum the inflammatory response shifted from acute to chronic upon aging. Macroglia, which showed a transient gliotic response after injury in young adult fish, displayed a permanent response in old animals. Overall, as in mammals, both a reduced intrinsic growth potential and a non‐supportive cellular environment, orchestrated by activated micro‐ and macroglia, were found to underlie the declined repair potential in aged killifish.To decode the cellular and molecular framework that defines visual system aging and the failed regenerative response in old fish, we are currently performing single‐cell RNA sequencing of the young adult and aged killifish retina. We envision our bioinformatic approaches to result in innovative druggable targets for future development of rejuvenative/curative therapies in the aged mammalian retina.In summary, our study highlights the importance of a neuron–glia crosstalk in health, disease and repair. It puts forward the strengths of the killifish as a vertebrate model with mammalian‐like characteristics upon aging, that offers unique opportunities to identify rejuvenating and neuroreparative strategies ensuring healthy aging.

Visual disorders and driving ability in persons with dementia: A mini review.

Impaired driving ability in patients with Alzheimer's disease (AD) is associated with a decline in cognitive processes and a deterioration of their basic sensory visual functions. Although a variety of ocular abnormalities have been described in patients with AD, little is known about the impact of those visual disorders on their driving performance. Aim of this mini-review is to provide an update on the driving ability of patients with dementia and summarize the primary visual disorders affecting their driving behavior. Databases were screened for studies investigating dementia, associated visual abnormalities and driving ability. There is consistent evidence that dementia affects driving ability. Patients with dementia present with a variety of visual disorders, such as visual acuity reduction, visual field defects, impaired contrast sensitivity, decline in color vision and age-related pathological changes, that may have a negative impact on their driving ability. However, there is a paucity in studies describing the impact of oculovisual decline on the driving ability of AD subjects. A bidirectional association between cognitive and visual impairment (VI) has been described. Given the bidirectional association between VI and dementia, vision screening and cognitive assessment of the older driver should aim to identify at-risk individuals and employ timely strategies for treatment of both cognitive and ocular problems. Future studies should characterize the basic visual sensory status of AD patients participating in driving studies, and investigate the impact of vision abnormalities on their driving performance.

The Angioid Streaks

Angioid streaks are a relatively rare complication and one of the etiologies of choroidal neovascularization. Asymptomatic at onset except at the complication stage where it is responsible for severe visual acuity decline with the macular syndrome. Diagnosis is clinically confirmed by angiography and OCT. Interest to propose a therapeutic adapted according to the localization and exudative phenomena of the neovessels. The prognosis is gloomy but seems improved by the arrival of anti-VEGF.

Association Between Rate of Ganglion Cell Complex Thinning and Rate of Central Visual Field Loss

Whether rapid ganglion cell complex (GCC) thinning during an initial follow-up period is associated with rates of central visual field loss over time is unclear but important to understand because risk of glaucoma progression can help guide treatment intensity. To investigate the association between the rate of GCC thinning during initial follow-up and the rate of central visual field loss. This retrospective cohort study assessed patients older than 18 years with glaucoma at a tertiary glaucoma center who were followed up from June 18, 2014, to January 11, 2019. Data analysis for the current study was undertaken in March 2022. Initial rates of GCC thinning were obtained from global GCC thickness values of the first 3 optical coherence tomography (OCT) scans. Rates of central visual field loss were assessed as the change in central (10-2) visual field mean deviation during the 4.7-year follow-up period by univariable and multivariable linear mixed-effects models. Eyes were categorized as slow (>-1 μm/y) or fast (≤-1 μm/y) progressors based on rates of GCC thinning. The cohort consisted of 202 eyes of 139 patients (mean [SD] age, 68.7 [10.0] years; 72 male [51.8%]); 44 African American patients (31.7%), 13 Asian patients (9.4%), 80 White patients (57.6%), and 2 patients who identified as other race and ethnicity (1.4%) were analyzed. The rate of GCC change was -0.56 μm/y (95% CI, -0.66 to -0.46 μm/y) during a mean initial follow-up of 1.8 years (95% CI, 1.7-2.0 years). A total of 163 eyes (80.7%) were slow OCT progressors, and 39 (19.3%) were fast OCT progressors, with rates of GCC thinning of -0.3 μm/y (95% CI, -0.4 to -0.2 μm/y) and -1.6 μm/y (-1.8 to -1.3 μm/y), respectively. The rates of 10-2 visual field mean deviation worsening among slow and fast OCT progressors were -0.10 dB/y (95% CI, -0.16 to 0.00 dB/y) and -0.34 dB/y (95% CI, -0.51 to -0.16 dB/y), respectively (difference, -0.26 dB/y; 95% CI, -0.45 to -0.07 dB/y; P = .008). In this cohort study, rapid GCC thinning during an initial follow-up period was associated with faster rates of central visual field decline. These findings support use of longitudinal macular OCT scans assisting clinical decision-making for glaucoma and also may guide possible intensification of therapy in high-risk patients.

Vision With Retrodots and Factors for Declining Visual Function.

We investigated decline in the visual function of eyes with retrodots (RDs)-a subtype of cataract. This study included 57 eyes with RD opacity only (mean age 72.3 ± 5.2 years) and 34 eyes with transparent lenses (mean age 71.4 ± 3.7 years). A physician diagnosed lens opacity. Using the Kanazawa Medical University Classification and Grading System, the eyes were classified into the RD-1 (37 eyes, RDs <25% of the 3-mm pupil area) and RD-2 (20 eyes, RDs ≥25% of the 3-mm pupil area) groups. Corrected distance visual acuity, contrast visual acuity, ocular refractive power, lens power, straylight, and backward light-scattering intensity and their relationship with visual function decline and optical characteristics of the eyeball were evaluated. Corrected distance visual acuity was significantly lower in the RD eyes than in controls. Contrast visual acuity decreased significantly in the RD-2 eyes in all environments and in the RD-1 eyes in the evening (EVE) and EVE + glare. Straylight was significantly higher in the RD-2 eyes than in the controls and RD-1 eyes but not different between the RD-1 eyes and controls. The RD-2 eyes were significantly more myopic than the controls and RD-1 eyes. When the opacity of RD eyes is ≥25%, the visual acuity and contrast visual acuity decrease and straylight increases. Furthermore, myopia occurs as the refractive power of the lens increases. Moreover, visual function decline may be due to an increase in the straylight value, which is necessary for determining surgical indications.

Older Adults' Response to Color Visibility in Indoor Residential Environment Using Eye-Tracking Technology.

Older adults spend relatively more time in indoor residential environments than young people. As their visual and cognitive abilities decline, they experience a high risk of accidents in indoor environments; thus, understanding their gaze behavior while considering cognitive capacity is essential in preventing potential accidents and planning for aging-friendly environments. The purpose of this study was to examine whether the use of color in living environments affects the visual attention of older adults. The following two experiments were conducted using eye-tracking technology: Experiment 1: Older adults' gaze behaviors were measured while viewing four images consisting of nine sets of door-door frames with different color combinations of safety colors, black and white; and Experiment 2: Based on results from Experiment 1, images of simulated living environments were created, and older adults' gaze behaviors were measured while viewing eight images in which two door colors were applied to verify spatial color visibility. Their cognitive state represented by the Mini-Mental State Examination (MMSE) was then compared with their gaze behavior. The results show that: (a) participants paid more attention to doors with color combinations including red (red-black and white-red) and remained longer on the red-black combination; (b) older adults looked at red-black doors faster than white doors in the same position; (c) the dwell time on a red-black door was longer than on that of the corresponding position of a white door; and (d) based on participants' MMSE values, the gaze behaviors of the group with low cognition were less focused and observable than those of the group with normal cognition. The results of this study are significant in that they reveal that indoor color can improve the visibility of elements that can impact safety in the living environments of older adults and enhance their quality of life.

Preliminary findings of accelerated visual memory decline and baseline brain correlates in middle-age and older adults with autism: The case for hippocampal free-water.

Research aimed at understanding cognitive and brain aging in adults with autism spectrum disorder (ASD) is growing, but critical longitudinal work is scant. Adults with ASD struggle with tasks involving visual memory compared with neurotypical adults (NT). This may be related to differences in size or integrity of the hippocampus and its' primary structural connectivity pathway, the fornix. The aim of this study was to describe preliminary findings of longitudinal aging trajectories in short- and long-term visual memory abilities in middle-age and older adults with ASD, compared with matched NT adults. We then evaluated baseline multi-modal imaging metrics of the hippocampal system, including the relatively novel metric of free-water, as potential correlates of longitudinal memory change in the ASD group. Middle-age and older adults with ASD (n = 25) and matched NT adults (n = 25) between the ages of 40 and 70 years were followed longitudinally at ~2-year intervals (range 2-5 years). Participants completed the Wechsler Memory Scale III Visual Reproduction task. Longitudinal mixed models were utilized to detect group differences in memory change with baseline age and sex as covariates. Hippocampal volume was measured via T1-weighted MRI images with FreeSurfer. Fornix fractional anisotropy and hippocampal and fornix free-water were measured from diffusion tensor imaging scans. Exploratory correlations were run between individual hippocampal system metrics and longitudinal slopes of visual memory change. There was a significant group by time interaction for long-term visual memory, such that middle-age and older adults with ASD declined faster than matched NT adults. There was no group by time interaction for short-term visual memory. Baseline hippocampal free-water was the only hippocampal system metric that correlated with long-term visual memory change in the ASD group. As one of the first longitudinal cognitive and brain aging studies in middle-age and older adults with ASD, our findings suggest vulnerabilities for accelerated long-term visual memory decline, compared to matched NT adults. Further, baseline hippocampal free-water may be a predictor of visual memory change in middle-age and older adults with ASD. These preliminary findings lay the groundwork for future prognostic applications of MRI for cognitive aging in middle-age and older adults with ASD.

ODP506 Posterior Staphyloma misdiagnosed as unilateral Grave's ophthalmopathy

Abstract 21 year old female presented to our clinic for management of "grave's disease" She was given diagnosis of Graves’ disease three years before presentation to our institution She was treated with PTU for 2-3 months then it was stopped On physical exam On physical exam she has a small diffused goiter Left eye was prominent without chemosis or lid lag Right eye was normal Decreased vision in the left eye, counting fingers only Thyroid function was normal Thyroid receptor antibody was negative Because of decline of vision and unilateral protrusion of Left eye she was referred to ophthalmology for further evaluation. MRI of the Orbits was ordered MRI revealed findings consistent with Staphyloma Staphyloma is a chronic eye condition which results from poor vision if left untreated and causes increase in AP diameter of eye which results in protrusion of eye which might be confused with grave's ophthalmopathy This diagnosis should be considered when patients present with unilateral ophthalmopathy, especially if there is significant decline in vision in the effected eye. Since she presented late in adulthood there is no treatment to improve her vision at this point From the thyroid standpoint she had negative thyroid antibodies and normal thyroid function Ultrasound of thyroid showed thyroid to be diffusely enlarged with homogenous texture Complete eye exam by ophthalmology is indicated in evaluation of ophthalmopathy especially in case of red flags like decreased vison or unilateral presentation With unilateral Ophthalmopathy MRI of the orbits should be part of the workup to exclude other etiologies such as retro-orbital tumors which may be confused with grave's ophthalmopathy. As evident in this case MRI revealed different diagnosis. Presentation: No date and time listed

The detection of vulnerable road users by younger and older drivers

The detection of vulnerable road users (VRUs), especially under time constraints, may be impaired in elderly drivers, due to their visual and cognitive decline. This represents a major concern for road safety. The objective of the present study was to investigate the effect of aging on the detection of VRUs. A further aim was to investigate the impact of external factors on VRU detection. Twenty-two young adults, 20 younger-old adults, and 32 older-old adults were included in the study. A series of photographs were displayed for 500 ms. Participants were asked to detect the VRU, which could be a motorcyclist, a cyclist, or a pedestrian. The VRU was located at one of two distances (near/far), one of two locations (off-centered/centered), and in two car-DRL (daytime running lights) environments (on/off). The ability to correctly detect a VRU was measured. An eye-tracker was used to record eye movements. The main findings showed that VRU-detection performance decreased with aging, even in the younger-old group (ages 55–68). The ability to correctly detect a VRU by older-old adults was poorer particularly when the VRU was a motorcyclist or a cyclist. As a whole, the older-old adults made more fixations to correctly detect the VRU than the other two age groups did. Moreover, the visual angle between the gaze of the participant’s last fixation and the target in the older-old group was lower than in the other two groups, particularly when the VRU was off-centered. This finding suggests that older-old adults compensated for their visual-field decline by doing more visual exploration than the other two groups did to correctly detect the VRU. The results are discussed with regards to age-related cognitive and visual deficits.Word count: 279.

Single-Cell Transcriptome of Wet AMD Patient-Derived Endothelial Cells in Angiogenic Sprouting.

Age-related macular degeneration (AMD) is a global leading cause of visual impairment in older populations. ‘Wet’ AMD, the most common subtype of this disease, occurs when pathological angiogenesis infiltrates the subretinal space (choroidal neovascularization), causing hemorrhage and retinal damage. Gold standard anti-vascular endothelial growth factor (VEGF) treatment is an effective therapy, but the long-term prevention of visual decline has not been as successful. This warrants the need to elucidate potential VEGF-independent pathways. We generated blood out-growth endothelial cells (BOECs) from wet AMD and normal control subjects, then induced angiogenic sprouting of BOECs using a fibrin gel bead assay. To deconvolute endothelial heterogeneity, we performed single-cell transcriptomic analysis on the sprouting BOECs, revealing a spectrum of cell states. Our wet AMD BOECs share common pathways with choroidal neovascularization such as extracellular matrix remodeling that promoted proangiogenic phenotype, and our ‘activated’ BOEC subpopulation demonstrated proinflammatory hallmarks, resembling the tip-like cells in vivo. We uncovered new molecular insights that pathological angiogenesis in wet AMD BOECs could also be driven by interleukin signaling and amino acid metabolism. A web-based visualization of the sprouting BOEC single-cell transcriptome has been created to facilitate further discovery research.