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Johnson TV, Calkins DJ, Fortune B, Goldberg JL, Torre AL, Lamba DA, Meyer JS, Reh TA, Wallace VA, Zack DJ, Baranov P. The importance of unambiguous cell origin determination in neuronal repopulation studies. iScience 2023;26(4):106361.Abstract
Neuronal repopulation achieved through transplantation or transdifferentiation from endogenous sources holds tremendous potential for restoring function in chronic neurodegenerative disease or acute injury. Key to the evaluation of neuronal engraftment is the definitive discrimination of new or donor neurons from preexisting cells within the host tissue. Recent work has identified mechanisms by which genetically encoded donor cell reporters can be transferred to host neurons through intercellular material transfer. In addition, labeling transplanted and endogenously transdifferentiated neurons through viral vector transduction can yield misexpression in host cells in some circumstances. These issues can confound the tracking and evaluation of repopulated neurons in regenerative experimental paradigms. Using the retina as an example, we discuss common reasons for artifactual labeling of endogenous host neurons with donor cell reporters and suggest strategies to prevent erroneous conclusions based on misidentification of cell origin.
Merabet LB, Manley CE, Pamir Z, Bauer CM, Skerswetat J, Bex PJ. Motion and form coherence processing in individuals with cerebral visual impairment. Dev Med Child Neurol 2023;65(10):1379-1386.Abstract
AIM: Using a visual psychophysical paradigm, we sought to assess motion and form coherence thresholds as indices of dorsal and ventral visual stream processing respectively, in individuals with cerebral visual impairment (CVI). We also explored potential associations between psychophysical assessments and brain lesion severity in CVI. METHOD: Twenty individuals previously diagnosed with CVI (mean age = 17 years 11 months [SD 5 years 10 months]; mean Verbal IQ = 86.42 [SD 35.85]) and 30 individuals with neurotypical development (mean age = 20 years 1 month [SD 3 years 8 months]; mean Verbal IQ = 110.05 [SD 19.34]) participated in the study. In this two-group comparison, cross-sectional study design, global motion, and form pattern coherence thresholds were assessed using a computerized, generalizable, self-administrable, and response-adaptive psychophysical paradigm called FInD (Foraging Interactive D-prime). RESULTS: Consistent with dorsal stream dysfunction, mean global motion (but not form) coherence thresholds were significantly higher in individuals with CVI compared to controls. No statistically significant association was found between coherence thresholds and lesion severity. INTERPRETATION: These results suggest that the objective assessment of motion and form coherence threshold sensitivities using this psychophysical paradigm may be useful in helping to characterize perceptual deficits and the complex clinical profile of CVI. WHAT THIS PAPER ADDS: In participants with cerebral visual impairment (CVI), motion (but not form) coherence thresholds were significantly higher compared to controls. These psychophysical results support the notion of dorsal stream dysfunction in CVI.
Yu C, Zou J, Ge Q-M, Liao X-L, Pan Y-C, Wu J-L, Su T, Zhang L-J, Liang R-B, Shao Y. Ocular microvascular alteration in Sjögren's syndrome treated with hydroxychloroquine: an OCTA clinical study. Ther Adv Chronic Dis 2023;14:20406223231164498.Abstract
BACKGROUND: Sjögren's syndrome (SjS) is a rare autoimmune disease, and despite our knowledge of SjS, we still lack effective treatments. Chloroquine drugs used to treat autoimmune diseases are still the primary medicine for SjS but increase the risk of chloroquine retinopathy. OBJECTIVES: The objective of this study is to use Optical Coherence Tomography Angiography (OCTA) images to monitor the microvascular changes in the fundus of SjS patients after hydroxychloroquine (HCQ) treatment and the feasibility of using them as diagnostic indicators. DESIGN: This is a retrospective observational cohort study. METHODS: Twelve healthy controls (HCs group; 24 eyes), 12 SjS patients (SjS group; 24 eyes), and 12 SjS patients treated with HCQ (HCQ group; 24 eyes) were recruited. Three-dimensional OCTA images of the retina were collected, and microvascular density was calculated for each eye. OCTA image segmentation for analysis was conducted using the central wheel division method (C1-C6), hemisphere segmentation method (SR, SL, IL, and IR), and the early treatment of diabetic retinopathy study method (ETDRS) (R, S, L, and I). RESULTS: Retinal microvascular density was significantly lower in the SjS patients compared to the HCs group (p < 0.05) and much lower in the HCQ group compared to the SjS patients (p < 0.05). The SjS and HCQ groups differed in the I, R, SR, IL, and IR regions in the superficial and deep retina and the S region in the superficial retina. The ROC curves of the relationship between the HCs and SjS groups and between the SjS and HCQ groups demonstrated good classification accuracy. CONCLUSION: HCQ may contribute significantly to the microvascular alteration in SjS. Microvascular alteration is a potential marker with adjunctive diagnostic value. The MIR and the OCTA images of I, IR, and C1 regions showed high accuracy in minoring the alteration.
Pakravan P, Patel V, Chau V, Rohowetz L, Lai J, Fan KC, Al-Khersan H, Melo IM, Muni RH, Tsao SW, Kaplan R, Jung JJ, Hoyek S, Patel NA, Kuriyan AE, Laura DM, Mantopoulos D, Syed ZA, Yannuzzi NA. Haptic Erosion Following Sutureless Scleral-fixated Intraocular Lens Placement. Ophthalmol Retina 2023;7(4):333-337.Abstract
PURPOSE: To describe the clinical features and visual outcomes of eyes with conjunctival haptic erosion after sutureless intrascleral (SIS) fixated intraocular lens (IOL) placement. DESIGN: Retrospective case series. SUBJECTS: Patients experiencing haptic erosion after SIS fixation between January 1, 2013, and March 1, 2022. METHODS: A multicenter, multisurgeon, retrospective review. MAIN OUTCOME MEASURES: Clinical features, visual outcomes, and treatment options following haptic erosions after SIS fixation. RESULTS: Nineteen eyes with haptic erosion were identified. The mean age at initial SIS fixation was 64 ± 12 years (range, 38-81 years). There were 5 (26%) eyes with a history of conjunctiva involving ocular surgery, including scleral buckle surgery and tube shunt surgery. Trocar-assisted fixation was performed in 15 (79%) eyes, whereas needle fixation was used in 4 (21%) eyes. Eighteen (95%) sets of haptics were flanged with a low temperature cautery. Seventeen (90%) sets of haptics were externalized superiorly and inferiorly, and 2 (10%) sets of haptics were externalized nasally and temporally. Haptics were covered by conjunctiva in 14 (74%) eyes and by scleral flap in 5 (26%) eyes. All patients experienced a single haptic erosion, of which 8 (43%) were located superiorly, 9 (47%) inferiorly, and 2 (10%) temporally. The mean interval between the initial SIS fixation and haptic erosion was 278 ± 437 days. After correction of the erosion, 18 (95%) eyes had a stable IOL at the last follow-up, with no recurrence of haptic erosion. In this series, there were no cases of endophthalmitis. CONCLUSIONS: Haptic erosion is a notable complication after SIS fixated IOL surgery but may be repaired with favorable visual outcomes. Careful evaluation of the conjunctiva should be considered before the surgery. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.
Ye JJ, Bouffard MA, Brooks E, Hung YP, Kimchi EY. Giant Cell Arteritis Presenting With Multiple Cranial Neuropathies - Case Report. Neurohospitalist 2023;13(2):188-191.Abstract
Background: Vision loss accounts for most ophthalmic presentations of giant cell arteritis (GCA), but an important minority of patients present with diplopia and other cranial neuropathies. Case study: Here we present the case of an 84-year-old woman with a prior history of multiple cancers who was admitted to our hospital after developing double vision. She was found to have mydriasis, ptosis, and ophthalmoplegia in the right eye (OD) consistent with a combined R CNIII/CNVI neuropathy, as well as highly elevated inflammatory markers. Given her cancer history, the patient was initially worked up for various neoplastic, paraneoplastic, inflammatory, and infectious causes of multiple cranial neuropathies; however, as these results were negative, GCA became a more likely contender as a possible rare cause of multiple cranial neuropathies. The patient underwent temporal artery biopsy which showed pathology consistent with giant cell arteritis, and she was treated with steroids with eventual improvement in ophthalmoplegia and ptosis. Conclusions: This case illustrates the importance of recognizing GCA as a rare possible cause of multiple cranial neuropathies, including the indispensable role of temporal artery biopsy.
Sun JA, Manz SN, Shen LQ. Glaucoma management in patients with penetrating keratoplasty or keratoprosthesis. Curr Opin Ophthalmol 2023;34(2):95-102.Abstract
PURPOSE OF REVIEW: Advances in surgical techniques and postoperative care have significantly improved rates of short-term complications following keratoplasty; however, glaucoma remains a highly prevalent long-term and potentially devastating complication for postkeratoplasty patients. In this review, we provide an overview of recent literature on glaucoma management in patients who have undergone penetrating keratoplasty or the Boston keratoprosthesis type I (KPro) implantation. RECENT FINDINGS: New research suggests an inflammatory cause underlying glaucoma following KPro. Accurate IOP measurement is difficult in patients postkeratoplasty; study of objective techniques such as PDCT or Tono-Pen in penetrating keratoplasty eyes and trans-palpebral Diaton tonometry in KPro eyes have shown promising results. Early glaucoma surgical intervention should be considered for patients undergoing penetrating keratoplasty and KPro. SUMMARY: Patients who have undergone penetrating keratoplasty or implantation of the Boston keratoprosthesis type I should be monitored frequently for elevated intraocular pressure and for other signs of glaucomatous optic nerve damage. Intraocular pressure elevation should be treated promptly either medically or surgically while minimizing risk to the corneal graft. Further research into inflammatory causes and other treatment modalities is promising for the long-term visual success in these patients.
Fu Z, Lundgren P, Pivodic A, Yagi H, Harman JC, Yang J, Ko M, Neilsen K, Talukdar S, Hellström A, Smith LEH. FGF21 via mitochondrial lipid oxidation promotes physiological vascularization in a mouse model of Phase I ROP. Angiogenesis 2023;26(3):409-421.Abstract
Hyperglycemia in early postnatal life of preterm infants with incompletely vascularized retinas is associated with increased risk of potentially blinding neovascular retinopathy of prematurity (ROP). Neovascular ROP (Phase II ROP) is a compensatory but ultimately pathological response to the suppression of physiological postnatal retinal vascular development (Phase I ROP). Hyperglycemia in neonatal mice which suppresses physiological retinal vascular growth is associated with decreased expression of systemic and retinal fibroblast growth factor 21 (FGF21). FGF21 administration promoted and FGF21 deficiency suppressed the physiological retinal vessel growth. FGF21 increased serum adiponectin (APN) levels and loss of APN abolished FGF21 promotion of physiological retinal vascular development. Blocking mitochondrial fatty acid oxidation also abolished FGF21 protection against delayed physiological retinal vessel growth. Clinically, preterm infants developing severe neovascular ROP (versus non-severe ROP) had a lower total lipid intake with more parenteral and less enteral during the first 4 weeks of life. Our data suggest that increasing FGF21 levels in the presence of adequate enteral lipids may help prevent Phase I retinopathy (and therefore prevent neovascular disease).
Patel V, Pakravan P, Lai J, Watane A, Mehra D, Eatz TA, Patel N, Yannuzzi NA, Sridhar J. Intraocular Lens Exchange: Indications, Comparative Outcomes by Technique, and Complications. Clin Ophthalmol 2023;17:941-951.Abstract
PURPOSE: To describe the indications, outcomes, and complications associated with intraocular lens (IOL) exchange. PATIENTS AND METHODS: To determine the relative frequency of postoperative complications between techniques for all patients undergoing IOL exchange from May 1, 2014 through August 31, 2020. RESULTS: IOL exchange was performed in 511 eyes of 489 patients (59.7% men; mean age: 67.0 ± 13.9 years, median time from cataract procedure to IOL exchange: 47.5 months). Mean uncorrected visual acuity significantly improved from 20/192 Snellen equivalent (logMAR 0.981) preoperatively to 20/61 (logMAR 0.487) at last follow-up (P < 0.001). Overall, 384 eyes (78.7%) met their desired refractive outcome within ±1.0 diopter (D). The most frequent complication was cystoid macular edema (CME) (n=39, 7.6%). Iris-sutured technique was associated with significantly greater frequency of subsequent IOL dislocation (10.3%) than 4-point scleral sutured (0%, P = 0.002), anterior chamber IOL (ACIOL, 1.5%, P = 0.01), and 2-point scleral sutured (0%, P = 0.03) techniques. Yamane scleral-fixation technique was associated with significantly greater frequency of developing IOL tilt (11.8%) than ACIOL (0%, P = 0.002), 4-point scleral sutured (1.1%, P = 0.01), 2-point scleral sutured (0%, P = 0.04), and iris-sutured (0%, P = 0.04) techniques. CONCLUSION: IOL exchange significantly improved uncorrected visual acuity and more than three-quarters of eyes met the refractive goal. Certain techniques were associated with complications, including subsequent dislocation associated with iris-sutured technique and IOL tilt associated with Yamane scleral-fixation technique. This information may help guide surgeons in deciding between procedural techniques for individual patients during IOL exchange preoperative planning.
Nirappel A, Klug E, Neeson C, Chachanidze M, El Helwe H, Hall N, Chang TC, Shen LQ, Solá-Del Valle D. Transscleral vs endoscopic cyclophotocoagulation: safety and efficacy when combined with phacoemulsification. BMC Ophthalmol 2023;23(1):129.Abstract
PURPOSE: To compare the effectiveness and safety of phacoemulsification combined with endoscopic cyclophotocoagulation (phaco/ECP), phacoemulsification combined with MicroPulse transscleral cyclophotocoagulation (phaco/MP-TSCPC), and phacoemulsification alone (phaco) in the treatment of coexisting cataract and glaucoma. METHODS: Retrospective cohort study of consecutive cases at Massachusetts Eye & Ear. The main outcome measures were the cumulative probabilities of failure between the phaco/ECP group, phaco/MP-TSCPC group, and the phaco alone group with failure defined as reaching NLP vision at any point postoperatively, undergoing additional glaucoma surgery, or the inability to maintain ≥ 20% IOP reduction from baseline with IOP between 5-18 mmHg while maintaining ≤ baseline medications. Additional outcome measures included changes in average IOP, number of glaucoma medications, and complication rates. RESULTS: Sixty-four eyes from 64 patients (25 phaco/ECP, 20 phaco/MPTSCPC, 19 phaco alone) were included in this study. The groups did not differ in age (mean 71.04 ± 6.7 years) or length of follow-up time. Baseline IOPs were significantly different between groups (15.78 ± 4.7 mmHg phaco/ECP, 18.37 ± 4.6 mmHg phaco/MP-TSCPC, 14.30 ± 4.2 mmHg phaco alone, p = 0.02). Primary open-angle glaucoma was the most common type of glaucoma in the phaco alone (42%) and phaco/ECP (48%) groups while mixed-mechanism glaucoma was the most common type in the phaco/MP-TSCPC group (40%). Surgical failure was less likely in eyes in the phaco/MP-TSCPC (3.40 times, p = 0.005) and phaco/ECP (1.40 times, p = 0.044) groups compared to phaco alone based on the Kaplan-Meier survival criteria. These differences maintained statistical significance when differences in preoperative IOP were taken into account using the Cox PH model (p = 0.011 and p = 0.004, respectively). Additionally, surgical failure was 1.98 times less likely following phaco/MP-TSCPC compared to phaco/ECP (p = 0.038). This difference only approached significance once differences in preoperative IOP were accounted for (p = 0.052). There was no significant difference in IOP reduction at 1 year between groups. Mean IOP reductions at 1 year were 3.07 ± 5.3 mmHg from a baseline of 15.78 ± 4.7 in the phaco/ECP group, 6.0 ± 4.3 mmHg from a baseline of 18.37 ± 4.6 in the phaco/MP-TSCPC group and 1.0 ± 1.6 from a baseline of 14.30 ± 4.2 mmHg in the phaco alone group. There were no differences in complication rates among the three groups. CONCLUSIONS: Both Phaco/MP-TSCPC and phaco/ECP appear to provide superior efficacy for IOP control when compared to phaco alone. All three procedures had similar safety profiles.
Waxman S, Quinn M, Donahue C, Falo LD, Sun D, Jakobs TC, Sigal IA. Individual astrocyte morphology in the collagenous lamina cribrosa revealed by multicolor DiOlistic labeling. Exp Eye Res 2023;230:109458.Abstract
Astrocytes in the lamina region of the optic nerve head play vital roles in supporting retinal ganglion cell axon health. In glaucoma, these astrocytes are implicated as early responders to stressors, undergoing characteristic changes in cell function as well as cell morphology. Much of what is currently known about individual lamina astrocyte morphology has been learned from rodent models which lack a defining feature of the human optic nerve head, the collagenous lamina cribrosa (LC). Current methods available for evaluation of collagenous LC astrocyte morphology have significant shortcomings. We aimed to evaluate Multicolor DiOlistic labeling (MuDi) as an approach to reveal individual astrocyte morphologies across the collagenous LC. Gold microcarriers were coated with all combinations of three fluorescent cell membrane dyes, DiI, DiD, and DiO, for a total of seven dye combinations. Microcarriers were delivered to 150 μm-thick coronal vibratome slices through the LC of pig, sheep, goat, and monkey eyes via MuDi. Labeled tissues were imaged with confocal and second harmonic generation microscopy to visualize dyed cells and LC collagenous beams, respectively. GFAP labeling of DiOlistically-labeled cells with astrocyte morphologies was used to investigate cell identity. 3D models of astrocytes were created from confocal image stacks for quantification of morphological features. DiOlistic labeling revealed fine details of LC astrocyte morphologies including somas, primary branches, higher-order branches, and end-feet. Labeled cells with astrocyte morphologies were GFAP+. Astrocytes were visible across seven distinct color channels, allowing high labeling density while still distinguishing individual cells from their neighbors. MuDi was capable of revealing tens to hundreds of collagenous LC astrocytes, in situ, with a single application. 3D astrocyte models allowed automated quantification of morphological features including branch number, length, thickness, hierarchy, and straightness as well as Sholl analysis. MuDi labeling provides an opportunity to investigate morphologies of collagenous LC astrocytes, providing both qualitative and quantitative detail, in healthy tissues. This approach may open doors for research of glaucoma, where astrocyte morphological alterations are thought to coincide with key functional changes related to disease progression.
Shah SS, Fulton A, Jabroun M, Brightman D, Simpson BN, Bodamer OA. Insights into the genotype-phenotype relationship of ocular manifestations in Kabuki syndrome. Am J Med Genet A 2023;191(5):1325-1338.Abstract
We aim to assess if genotype-phenotype correlations are present within ocular manifestations of Kabuki syndrome (KS) among a large multicenter cohort. We conducted a retrospective, medical record review including clinical history and comprehensive ophthalmological examinations of a total of 47 individuals with molecularly confirmed KS and ocular manifestations at Boston Children's Hospital and Cincinnati Children's Hospital Medical Center. We assessed information regarding ocular structural, functional, and adnexal elements as well as pertinent associated phenotypic features associated with KS. For both type 1 KS (KS1) and type 2 KS (KS2), we observed more severe eye pathology in nonsense variants towards the C-terminus of each gene, KMT2D and KDM6A, respectively. Furthermore, frameshift variants appeared to be not associated with structural ocular elements. Between both types of KS, ocular structural elements were more frequently identified in KS1 compared with KS2, which only involved the optic disc in our cohort. These results reinforce the need for a comprehensive ophthalmologic exam upon diagnosis of KS and regular follow-up exams. The specific genotype may allow risk stratification of the severity of the ophthalmologic manifestation. However, additional studies involving larger cohorts are needed to replicate our observations and conduct powered analyses to more formally risk-stratify based on genotype, highlighting the importance of multicenter collaborations in rare disease research.
Yu XT, Rong SS. Genome-Wide Associations and Confirmatory Meta-Analyses in Diabetic Retinopathy. Genes (Basel) 2023;14(3)Abstract
The present study aimed to summarize and validate the genomic association signals for diabetic retinopathy (DR), proliferative DR, and diabetic macular edema/diabetic maculopathy. A systematic search of the genome-wide association study (GWAS) catalog and PubMed/MELINE databases was conducted to curate a comprehensive list of significant GWAS discoveries. The top signals were then subjected to meta-analysis using established protocols. The results indicate the need for improved consensus among DR GWASs, highlighting the importance of validation efforts. A subsequent meta-analysis confirmed the association of two SNPs, rs4462262 (ZWINT-MRPS35P3) (odds ratio = 1.38, p = 0.001) and rs7903146 (TCF7L2) (odd ratio = 1.30, p < 0.001), with DR in independent populations, strengthening the evidence of their true association. We also compiled a list of candidate SNPs for further validation. This study highlights the importance of consistent validation and replication efforts in the field of DR genetics. The two identified gene loci warrant further functional investigation to understand their role in DR pathogenesis.
Resnick HH, Bear MF, Gaier ED. Partial Recovery of Amblyopia After Fellow Eye Ischemic Optic Neuropathy. J Neuroophthalmol 2023;43(1):76-81.Abstract
BACKGROUND: Recovery from amblyopia in adulthood after fellow eye (FE) vision loss is a well-known phenomenon. Incidence of recovery varies widely following different FE pathologies, and the rate of recovery after FE ischemic optic neuropathy (ION) has not been examined. We aimed to determine the frequency and degree of improvement in amblyopic eye (AE) visual function after ION in the FE. METHODS: We performed a retrospective chart review of patients between 2007 and 2021 confirmed to have amblyopia and ischemic optic neuropathy in different eyes. Patients with unstable ocular pathology potentially limiting vision were excluded. We compared the best-corrected visual acuity (VA) in each eye before and after FE ION over time. For patients with available data, we examined change in perimetric performance over time. RESULTS: Among the 12 patients who met the inclusion criteria (mean age 67 ± 8 years), 9 (75%) improved ≥1 line and 2 (17%) improved ≥3 lines. The median time from ION symptom onset to maximal improvement was 6 months (range: 2-101 months). Reliable perimetric data were available for 6 patients. Mean sensitivity improved in the AE for all patients, with mean improvement of 1.9 ± 1.1 dB. There was no correspondence between foci of ION-related field loss and gains in field sensitivity in the AE. CONCLUSIONS: A high proportion of patients with amblyopia and contralateral ION experience improvement in AEVA. Modest gains in perimetric sensitivity in the AE may accompany FE ION. These findings support the view that residual plasticity in the adult visual cortex can be tapped to support functional improvement in amblyopia.
Philip AM, Fernandez-Santos CC, Ramezani K, Dolinko AH, Manhapra A, Look-Why S, Chang PY, Foster SC, Anesi SD. Ocular Mucus Membrane Pemphigoid: A Primary Versus Secondary Entity. Cornea 2023;42(3):280-283.Abstract
PURPOSE: The purpose of this review was to investigate the idea that inflammatory events of the conjunctiva and ocular surface may act as triggering events for the onset of ocular mucus membrane pemphigoid (oMMP). METHODS: A retrospective chart review of patients with biopsy-proven oMMP and no systemic pemphigoid disease. The presence, or absence, of the following inflammatory conditions at the time of OMMP diagnosis was noted: significant eyelid disease, significant atopic eye disease, Stevens-Johnson syndrome, graft-versus-host disease, viral keratitis, sarcoidosis with ocular involvement, chemical burns, medicamentosa, Sjogren syndrome, systemic lupus erythematosus with ocular involvement, and epidemic keratoconjunctivitis. Response to immunomodulatory therapy (IMT) was also recorded. RESULTS: A total of 779 patient records were identified. Conjunctival biopsy was present in 724 patients, with 646 (89.2%) being positive. One hundred thirty-nine patients (21.5%) with positive biopsies had extraocular pemphigoid disease and were excluded from further analysis. Of the 507 included patients, 154 (30.4%) had at least one of the specified inflammatory conditions present at the time of OMMP diagnosis. One hundred eighteen patients (23.3%) had only 1 such condition, 35 (6.9%) had 2, and 1 patient had 3. In patients with at least one of these conditions present, response to IMT was seen in 84.9% of patients with sufficient follow-up. CONCLUSIONS: Our study suggests that oMMP may arise as a secondary pathology to acute inflammatory events or chronic inflammatory states of the conjunctiva and ocular surface.
Yadav AK, Choudhary SS, Pawar NM, Velaga NR. Investigating the role of beliefs in influencing the hand-held and hands-free mobile phone use among pedestrians in India. Int J Inj Contr Saf Promot 2023;30(1):79-90.Abstract
Mobile phone distraction is a significant contributor to pedestrian injuries. However, mobile phone engagement among pedestrians has been scarcely explored in a developing country like India. The present study utilized the beliefs-based theory of planned behaviour to examine the association between pedestrian beliefs towards distracted walking (behavioural, normative, and control) and their mobile phone use frequencies. Based on a survey of 560 pedestrians (64.6% males), it was found that the major use of mobile phones was for listening to music (30.7%), followed by receiving a call (25%), making a call (18.9%), texting (9.8%), navigation (8.5%) and internet browsing (7.1%). A series of multivariate ANOVAs and logistic regression models were developed to investigate the relationships between the beliefs and frequencies of mobile phone use in hands-free and hand-held conditions. Significant multivariate differences were found for behavioural and normative beliefs in hands-free conditions and all three types of beliefs in hand-held conditions. The frequency of mobile phone use was significantly predicted by normative beliefs (p < 0.001) in the hands-free condition, and by behavioural (p = 0.041) and normative beliefs (p = 0.004) in the hand-held condition. The findings may assist the road safety countermeasures in addressing the issue of pedestrian distraction.

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