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    Research Update 587


    Virtual reality as a means to explore assistive technologies for the visually impaired.

    PLOS digital health. 2023 Jun 20;

    Ricci FS, Boldini A, Ma X, Beheshti M, Geruschat DR, Seiple WH, Rizzo JR, Porfiri M.

    Visual impairment represents a significant health and economic burden affecting 596 million globally. The incidence of visual impairment is expected to double by 2050 as our population ages. Independent navigation is challenging for persons with visual impairment, as they often rely on non-visual sensory signals to find the optimal route. In this context, electronic travel aids are promising solutions that can be used for obstacle detection and/or route guidance. However, electronic travel aids have limitations such as low uptake and limited training that restrict their widespread use. Here, we present a virtual reality platform for testing, refining, and training with electronic travel aids. We demonstrate the viability on an electronic travel aid developed in-house, consist of a wearable haptic feedback device. We designed an experiment in which participants donned the electronic travel aid and performed a virtual task while experiencing a simulation of three different visual impairments: age-related macular degeneration, diabetic retinopathy, and glaucoma. Our experiments indicate that our electronic travel aid significantly improves the completion time for all the three visual impairments and reduces the number of collisions for diabetic retinopathy and glaucoma. Overall, the combination of virtual reality and electronic travel aid may have a beneficial role on mobility rehabilitation of persons with visual impairment, by allowing early-phase testing of electronic travel aid prototypes in safe, realistic, and controllable settings.

    DOI: 10.1371/journal.pdig.0000275


    Ten-year visual outcome and change in chorioretinal atrophy after intravitreal ranibizumab for macular neovascularization in pathologic myopia.

    Retina (Philadelphia, Pa.) 2023 Jun 16.

    Sakata R, Miyata M, Ooto S, Tamura H, Ueda-Arakawa N, Muraoka Y, Miyake M, Hata M, Takahashi A, Kido A, Numa S, Mori Y, Tsuda K, Uji A, Oishi A, Tsujikawa A.

    Purpose: To investigate the 10-year visual outcome and chorioretinal atrophy after a single intravitreal ranibizumab injection (IVR) followed by a pro re nata (PRN) regimen for myopic macular neovascularization (mMNV) in pathologic myopia, and to identify the factors associated with 10-year best-corrected visual acuity (BCVA).

    Methods: This retrospective observational study evaluated 26 consecutive treatment-naïve eyes (26 patients) with mMNV in pathologic myopia who underwent a single IVR followed by a PRN regimen of IVR and/or intravitreal aflibercept injection and observed over 10 years. We assessed changes in BCVA and morphological parameters, including the META-PM Study category as a chorioretinal atrophy index.

    Results: The logarithm of the minimum angle of resolution BCVA changed from 0.36 (Snellen, 20/45) ± 0.39 to 0.39 (20/49) ± 0.36 over 10 years of observation. Compared to baseline, 1-year BCVA improved (P = 0.002), whereas 2-10-year BCVA was not significantly different. Total injection frequency was 3.8 ± 2.6. In none of the eyes, 10-year BCVA was 20/200 or less. Ten-year BCVA correlated with baseline BCVA (P = 0.01, r = 0.47). The META-PM Study category progressed in 60% of eyes. There were no drug-induced complications.

    Conclusions: BCVA in eyes with mMNV in pathologic myopia was maintained for 10 years after a single IVR followed by a PRN regimen without drug-induced complications. The META-PM Study category progressed in 60% of eyes, especially those with older baseline age. Early diagnosis and treatment of mMNV are essential to maintain good long-term BCVA.

    DOI: 10.1097/IAE.0000000000003869


    Integrating genetics and metabolomics from multi-ethnic and multi-fluid data reveals putative mechanisms for age-related macular degeneration.

    Cell reports. Medicine. 2023 Jun 13:

    Han X, Lains I, Li J, Li J, Chen Y, Yu B, Qi Q, Boerwinkle E, Kaplan R, Thyagarajan B, Daviglus M, Joslin CE, Cai J, Guasch-Ferré M, Tobias DK, Rimm E, Ascherio A, Costenbader K, Karlson E, Mucci L, Eliassen AH, Zeleznik O, Miller J, Vavvas DG, Kim IK, Silva R, Miller J, Hu F, Willett W, Lasky-Su J, Kraft P, Richards JB, MacGregor S, Husain D, Liang L.

    Age-related macular degeneration (AMD) is a leading cause of blindness in older adults. Investigating shared genetic components between metabolites and AMD can enhance our understanding of its pathogenesis. We conduct metabolite genome-wide association studies (mGWASs) using multi-ethnic genetic and metabolomic data from up to 28,000 participants. With bidirectional Mendelian randomization analysis involving 16,144 advanced AMD cases and 17,832 controls, we identify 108 putatively causal relationships between plasma metabolites and advanced AMD. These metabolites are enriched in glycerophospholipid metabolism, lysophospholipid, triradylcglycerol, and long chain polyunsaturated fatty acid pathways. Bayesian genetic colocalization analysis and a customized metabolome-wide association approach prioritize putative causal AMD-associated metabolites. We find limited evidence linking urine metabolites to AMD risk. Our study emphasizes the contribution of plasma metabolites, particularly lipid-related pathways and genes, to AMD risk and uncovers numerous putative causal associations between metabolites and AMD risk.

    DOI: 10.1016/j.xcrm.2023.101085

    Association of oral montelukast with reduced odds of developing exudative age-related macular degeneration.

    Retina (Philadelphia, Pa.) 2023 Jun 16.

    Matsumiya W, Karaca I, Pham BH, Akhavanrezayat A, Uludag G, Yasar C, Ghoraba H, Mobasserian A, Regenold J, Halim MS, Sepah YJ, Do DV, Chong V, Nguyen QD.

    Purpose: This study was conducted to evaluate the association of oral montelukast, selective antagonism for cysteinyl leukotriene receptor 1, with reduced odds of exudative age-related macular degeneration (exAMD) development.

    Methods: This case-control study was conducted using Institutional Cohort Finder tool, and included 1913 patients with exAMD (ICD: H35.32 and 362.52) and 1913 age- and gender-matched control subjects without exAMD. Sub-analysis among 1913 exAMD and 324 non-exudative AMD was also conducted.

    Results: A total of 47 (2.5%) exAMD cases were identified to have a history of oral montelukast use prior to exAMD diagnosis, compared to 84 (4.4%) controls. Montelukast usage was significantly associated with reduced odds of exAMD in the multivariable analysis (adjusted OR: 0.50, 95% CI: 0.31 – 0.80) as well as NSAID usage (adjusted OR: 0.69). Caucasian race, history of smoking, non-exudative macular degeneration in either eye were also found to have significant relationship with increased odds of exAMD. In the sub-analysis, montelukast usage showed significant association with reduced odds of developing exAMD from non-exudative AMD (adjusted OR: 0.53 95% CI: 0.29 – 0.97) as well as the presence of atopic disease (adjusted OR: 0.60).

    Conclusion: The study results suggested that oral montelukast is linked to reduced odds of exAMD development.

    DOI: 10.1097/IAE.0000000000003870


    Deep survival modeling of longitudinal retinal OCT volumes for predicting the onset of atrophy in patients with intermediate AMD.

    Biomedical optics express. 2023 May 2;

    Rivail A, Vogl WD, Riedl S, Grechenig C, Coulibaly LM, Reiter GS, Guymer RH, Wu Z, Schmidt-Erfurth U, Bogunović H.

    In patients with age-related macular degeneration (AMD), the risk of progression to late stages is highly heterogeneous, and the prognostic imaging biomarkers remain unclear. We propose a deep survival model to predict the progression towards the late atrophic stage of AMD. The model combines the advantages of survival modelling, accounting for time-to-event and censoring, and the advantages of deep learning, generating prediction from raw 3D OCT scans, without the need for extracting a predefined set of quantitative biomarkers. We demonstrate, in an extensive set of evaluations, based on two large longitudinal datasets with 231 eyes from 121 patients for internal evaluation, and 280 eyes from 140 patients for the external evaluation, that this model improves the risk estimation performance over standard deep learning classification models.

    DOI: 10.1364/BOE.487206


    Evaluation of visual acuity in dry AMD patients after microcurrent electrical stimulation.

    International journal of retina and vitreous. 2023 Jun 18;

    Parkinson KM, Sayre EC, Tobe SW.

    Background: To assess micro current to improve vision for dry age-related macular degeneration. Dry age-related macular degeneration is a major cause of blindness, disability, and severe erosion of quality of life, throughout the world. Beyond nutritional supplementation, there is no approved therapy.

    Methods: This was a prospective randomized sham controlled clinical trial for participants with confirmed dry AMD with documented visual loss. Participants were randomized three to one, to receive transpalpebral external micro current electrical stimulation with the MacuMira device. The Treatment group received four treatments in the first two weeks, and two further treatments at weeks 14 and 26. Differences in BCVA and contrast sensitivity (CS) were estimated with mixed-effects repeated measures analysis of variance.

    Results: Change of visual acuity with ETDRS assessment of number of letters read (NLR) and contrast sensitivity at week 4 and 30, compared to the first visit, between 43 treatment and 19 sham control participants. The Sham Control group had NLR of 24.2 (SD 7.1) at baseline, 24.2 (SD 7.2) at 4 weeks, and 22.1 (SD7.4) at 30 weeks. The Treatment group had NLR of 19.6 (SD 8.9) at baseline, 27.6 (SD 9.1) at 4 weeks, and 27.8 (SD 8.4) at 30 weeks. The change in NLR from baseline in the Treatment compared to the Sham control group was 7.7 (95% CI 5.7, 9.7, p < 0.001) at 4 weeks and 10.4 (95% CI 7.8, 13.1, p < 0.001) at 30 weeks. There were similar benefits in CS.

    Conclusions: This pilot study of transpalpebral microcurrent demonstrated improved visual measures and is very encouraging as a potential treatment for dry AMD.

    DOI: 10.1186/s40942-023-00471-y


    Impact of an immersive, interactive medical education initiative on guideline-based retinal disease management knowledge/competence and effectual practice change.

    BMC Ophthalmology. 2023 Jun 22;

    Singh RP, Welch L, Longo NL, Frese M.

    Background: Retinal diseases, including wet or dry age-related macular degeneration, diabetic macular edema, and diabetic retinopathy (DR), are underdiagnosed and undertreated in the United States. Clinical trials support the effectiveness of anti-vascular endothelial growth factor (anti-VEGF) therapies for several retinal conditions, but real-world data suggest underuse by clinicians, resulting in patients experiencing poorer visual outcomes over time. Continuing education (CE) has demonstrated effectiveness at changing practice behaviors, but more research is needed to understand whether CE can help address diagnostic and treatment gaps.

    Methods: This test and control matched pair analysis examined pre-/post-test knowledge of retinal diseases and guideline-based screening and intervention among 10,786 healthcare practitioners (i.e., retina specialists, ophthalmologists, optometrists, primary care providers, diabetes educators, pharmacists/managed care specialists, and other healthcare providers, such as registered nurses, nurse practitioners, and physician assistants) who participated in a modular, interactive CE initiative. An additional medical claims analysis provided data on practice change, evaluating use of VEGF-A inhibitors among retina specialist and ophthalmologist learners (n = 7,827) pre-/post-education, compared to a matched control group of non-learners. Outcomes were pre-/post-test change in knowledge/competence and clinical change in application of anti-VEGF therapy, as identified by the medical claims analysis.

    Results: Learners significantly improved knowledge/competence scores on early identification and treatment, identifying patients who could benefit from anti-VEGF agents, using guideline-recommended care, recognizing the importance of screening and referral, and recognizing the importance of early detection and care for DR (all P-values = 0.003 to 0.004). Compared with matched controls, learners’ incremental total injections for anti-VEGF agents for retinal conditions increased more after the CE intervention (P < 0.001); specifically, there were 18,513 more (new) anti-VEGF injections prescribed versus non-learners (P < 0.001).

    Conclusions: This modular, interactive, immersive CE initiative resulted in significant knowledge/competence gains among retinal disease care providers and changes in practice-related treatment behaviors (i.e., appropriate consideration and greater incorporation of guideline-recommended anti-VEGF therapies) among participating ophthalmologists and retina specialists compared to matched controls. Future studies will utilize medical claims data to show longitudinal impact of this CE initiative on treatment behavior among specialists and impact on diagnosis and referral rates among optometrists and primary care providers who participate in future programming.

    DOI: 10.1186/s12886-023-03034-9


    Nicotinamide mononucleotide, a potential future treatment in ocular diseases.

    Graefe’s archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie. 2023 Jun 19.

    Lee D, Tomita Y, Shinojima A, Ban N, Yamaguchi S, Nishioka K, Negishi K, Yoshino J, Kurihara T.

    Purpose: The burden of ocular diseases has been gradually increasing worldwide. Various factors are suggested for the development and progression of ocular diseases, such as ocular inflammation, oxidative stress, and complex metabolic dysregulation. Thus, managing ocular diseases requires the modulation of pathologic signaling pathways through many mechanisms. Nicotinamide mononucleotide (NMN) is a bioactive molecule naturally found in life forms. NMN is a direct precursor of the important molecule nicotinamide adenine dinucleotide (NAD+), an essential co-enzyme required for enormous cellular functions in most life forms. While the recent experimental evidence of NMN treatment in various metabolic diseases has been well-reviewed, NMN treatment in ocular diseases has not been comprehensively summarized yet. In this regard, we aimed to focus on the therapeutic roles of NMN treatment in various ocular diseases with recent advances.

    Methods: How we came to our current opinion with a recent summary was described based on our own recent reports as well as a search of the related literature.

    Results: We found that NMN treatment might be available for the prevention of and protection from various experimental ocular diseases, as NMN treatment modulated ocular inflammation, oxidative stress, and complex metabolic dysregulation in murine models for eye diseases such as ischemic retinopathy, corneal defect, glaucoma, and age-related macular degeneration.

    Conclusion: Our current review suggests and discusses new modes of actions of NMN for the prevention of and protection from various ocular diseases and can urge future research to obtain more solid evidence on a potential future NMN treatment in ocular diseases at the preclinical stages.

    DOI: 10.1007/s00417-023-06118-w