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Background: People on the kidney waitlist are less informed about potential suspensions. Disparities may exist among those who are suspended and who return to the waitlist. We evaluated the patient journey after entering the waitlist, including suspensions and outcomes, and factors associated with these transitions., Methods: We included all incident patients waitlisted for their first transplant from deceased donors in Australia from 2006 to 2019. We described all clinical transitions after entering the waitlist. We predicted the restricted mean survival time (unadjusted and adjusted) until first transplant by the number of prior suspensions. We evaluated factors associated with transitions using flexible survival models and clinical endpoints using Cox models., Results: Of 8466 patients waitlisted and followed over 45 757.4 person-years (median 4.8 years), 6741 (80%) were transplanted, 381 (5%) died waiting and 1344 (16%) were still waiting. A total of 3127 (37%) people were suspended at least once. Predicted mean time from waitlist to transplant was 3.0 years [95% confidence interval (CI) 2.8-3.2] when suspended versus 1.9 years (95% CI 1.8-1.9) when never suspended. Prior suspension increased the likelihood of further suspensions 4.2-fold (95% CI 3.8-4.6) and returning to the waitlist by 50% (95% CI 36-65) but decreased the likelihood of transplantation by 29% (95% CI 62-82). Death risk while waiting was increased 12-fold (95% CI 8.0-18.3) when currently suspended. Australian non-Indigenous males were 13% [hazard ratio (HR) 1.13 (95% CI 1.04-1.23)] and Asian males 23% [HR 1.23 (95% CI 1.06-1.42)] more likely to return to the waitlist compared with females of the same ethnicity., Conclusion: The waitlist journey was not straightforward. Suspension was common, impacted the chance of transplantation and meant waiting an average of 1 year longer until transplant. We have provided estimates for and factors associated with suspension, relisting and outcomes after waitlisting to support more informed discussions. This evidence is critical to further understand drivers of inequitable access to transplantation., (© The Author(s) 2023. Published by Oxford University Press on behalf of the ERA.)

Introduction: Brain metastases commonly occur in patients with non-small cell lung cancer (NSCLC). Standard first-line treatment for NSCLC, without an EGFR, ALK or ROS1 mutation, is either chemoimmunotherapy or anti-PD-1 monotherapy. Traditionally, patients with symptomatic or untreated brain metastases were excluded from the pivotal clinical trials that established first-line treatment recommendations. The intracranial effectiveness of these treatment protocols has only recently been elucidated in small-scale prospective trials., Methods: Patients with NSCLC and brain metastases, treated with first-line chemoimmunotherapy or anti-PD-1 monotherapy were selected from the Australian Registry and biObank of thoracic cancers (AURORA) clinical database covering seven institutions. The primary outcome was a composite time-to-event (TTE) outcome, including extracranial and intracranial progression, death, or need for local intracranial therapy, which served as a surrogate for disease progression. The secondary outcome included overall survival (OS), intracranial objective response rate (iORR) and objective response rate (ORR)., Results: 116 patients were included. 63% received combination chemoimmunotherapy and 37% received anti-PD-1 monotherapy. 69% of patients received upfront local therapy either with surgery, radiotherapy or both. The median TTE was 7.1 months (95% CI 5 - 9) with extracranial progression being the most common progression event. Neither type of systemic therapy or upfront local therapy were predictive of TTE in a multivariate analysis. The median OS was 17 months (95% CI 13-27). Treatment with chemoimmunotherapy was predictive of longer OS in multivariate analysis (HR 0.35; 95% CI 0.14 - 0.86; p=0.01). The iORR was 46.6%. The iORR was higher in patients treated with chemoimmunotherapy compared to immunotherapy (58% versus 31%, p=0.01). The use of chemoimmunotherapy being predictive of iORR in a multivariate analysis (OR 2.88; 95% CI 1.68 - 9.98; p=0.04)., Conclusion: The results of this study of real-world data demonstrate the promising intracranial efficacy of chemoimmunotherapy in the first-line setting, potentially surpassing that of immunotherapy alone. No demonstrable difference in survival or TTE was seen between receipt of upfront local therapy. Prospective studies are required to assist clinical decision making regarding optimal sequencing of local and systemic therapies., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Brown, Khou, Brown, Alexander, Jayamanne, Wei, Gray, Chan, Smith, Harden, Mersiades, Warburton, Itchins, Lee, Pavlakis, Clarke, Boyer, Nagrial, Hau, Pires da Silva, Kao and Kong.)

This study sought to identify demographic variations in retinal thickness measurements from optical coherence tomography (OCT), to enable the calculation of cell density parameters across the neural layers of the healthy human macula. From macular OCTs (n = 247), ganglion cell (GCL), inner nuclear (INL), and inner segment-outer segment (ISOS) layer measurements were extracted using a customized high-density grid. Variations with age, sex, ethnicity, and refractive error were assessed with multiple linear regression analyses, with age-related distributions further assessed using hierarchical cluster analysis and regression models. Models were tested on a naïve healthy cohort (n = 40) with Mann-Whitney tests to determine generalizability. Quantitative cell density data were calculated from histological data from previous human studies. Eccentricity-dependent variations in OCT retinal thickness closely resemble topographic cell density maps from human histological studies. Age was consistently identified as significantly impacting retinal thickness (p = .0006, .0007, and .003 for GCL, INL and ISOS), with gender affecting ISOS only (p < .0001). Regression models demonstrated that age-related changes in the GCL and INL begin in the 30th decade and were linear for the ISOS. Model testing revealed significant differences in INL and ISOS thickness (p = .0008 and .0001; however, differences fell within the OCT's axial resolution. Qualitative comparisons show close alignment between OCT and histological cell densities when using unique, high-resolution OCT data, and correction for demographics-related variability. Overall, this study describes a process to calculate in vivo cell density from OCT for all neural layers of the human retina, providing a framework for basic science and clinical investigations., (© 2023 The Authors. The Journal of Comparative Neurology published by Wiley Periodicals LLC.)

Purpose: The aim of this study was to investigate the reliability of subbasal corneal nerve plexus parameters of the inferior whorl compared with the central cornea with in vivo corneal confocal microscopy and to investigate the impact of inferior whorl pattern complexity on reproducibility., Methods: Subbasal corneal nerves of healthy controls (n = 10) and patients with chemotherapy-induced peripheral neuropathy (n = 10) were imaged with a laser scanning confocal microscope. Two masked, experienced observers and the original image taker were tasked with selecting representative images of the central cornea and inferior whorl for each participant. This was conducted on 2 occasions 1 week apart. Corneal nerve fiber length (CNFL) and fractal dimension (CNFrD) [central cornea: CNFL and CNFrD; inferior whorl region: inferior whorl length (IWL) and inferior whorl fractal dimension (IWFrD)] were analyzed. Intraclass correlation coefficient (ICC) was analyzed for interobserver and intraobserver reliability. Inferior whorl complexity was classified according to the ease of identification of the center point of convergence., Results: Interobserver ICC was 0.992 for CNFL, 0.994 for CNFrD, 0.980 for IWL, and 0.954 for IWFrD. When analyzed by inferior whorl complexity, the interobserver reliability was similar for simple (0.987 for IWL; 0.960 for IWFrD) and complex patterns (0.967 for IWL; 0.949 for IWFrD). However, intraobserver ICC were reduced for complex (IWL 0.841-0.970; IWFrD 0.830-0.955) compared with simple patterns (IWL 0.931-0.970; IWFrD 0.921-0.969)., Conclusions: Although the overall interobserver reliability was excellent for the central corneal and inferior whorl parameters, there was lower intraobserver reliability for the inferior whorl parameters for complex morphological patterns. To improve reliability, more sophisticated wide-field imaging of the inferior whorl may be needed., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Clinical Relevance: There is potential benefit in analysing corneal nerve tortuosity as a marker for assessment and progression of systemic diabetic neuropathy., Background: The aim of this work was to determine whether tortuosity significantly differs in participants with type 1 (T1DM) and type 2 (T2DM) diabetes compared to controls and whether tortuosity differed according to neuropathy status., Methods: Corneal nerves of 164 participants were assessed across T1DM, T2DM and control groups. Images of corneal nerves were captured via in vivo corneal confocal microscopy. Diabetic neuropathy status was examined using the Total Neuropathy Score (TNS). Tortuosity was assessed with Cfibre v0.097. Results were compared between groups with a linear mixed model accounting for location of image and controlling for age, producing Tortuosity Factor (TF), an estimate of the marginal means of each group., Results: Tortuosity was significantly reduced in the T1DM group compared to controls (TF = 0.241, 95%CI = 0.225-0.257 vs. TF = 0.272, 95%CI = 0.252-0.292; mean difference = -0.031, p = 0.02) and in the T2DM group compared to controls (TF = 0.261, 95%CI = 0.244-0.278 vs. TF = 0.289, 95%CI = 0.270-0.308; mean difference = -0.029, p = 0.03). Tortuosity did not significantly differ between participants with T1DM and T2DM accounting for age and TNS (TF = 0.240, 95%CI = 0.215-0.265 vs. 0.269, 95%CI = 0.244-0.293, mean difference = -0.029, p = 0.11). Tortuosity was significantly reduced in participants with neuropathy (TNS≥2) compared to participants with no neuropathy (TNS< 2) (TF = 0.248, 95%CI = 0.231-0.265 vs. TF = 0.272, 95%CI = 0.260-0.283; mean difference = -0.024, p = 0.03)., Conclusions: Tortuosity is significantly reduced in participants with T1DM and T2DM compared to age matched controls and in participants with neuropathy compared to those without neuropathy.

Aim: Cardiovascular mortality risk evolves over the lifespan of kidney failure (KF), as patients develop comorbid disease and transition between treatment modalities. Absolute cardiovascular death rates would help inform clinical practice and health-care provision, but are not well understood across a continuum of dialysis and transplant states. We aimed to characterize cardiovascular death across the natural history of KF using a lifespan approach., Methods: We performed a population-based cohort study of incident patients commencing kidney replacement therapy in Australia and New Zealand. Cardiovascular deaths were identified using data linkage to national death registers. We estimated the probability of death and kidney transplant using multi-state models, and calculated rates of graft failure and cardiovascular death across demographic factors and comorbidities., Results: Among 60 823 incident patients followed over 381 874 person-years, 25% (8492) of deaths were from cardiovascular disease. At 15 years from treatment initiation, patients had a 15.2% probability of cardiovascular death without being transplanted, but only 2.3% probability of cardiovascular death post-transplant. Females had a 3% lower probability of cardiovascular death at 15 years (15.3% vs. 18.6%) but 4% higher probability of non-cardiovascular death (54.5% vs. 50.8%). Within the first year of dialysis, cardiovascular mortality peaked in the second month and showed little improvement across treatment era., Conclusion: Despite improvements over time, cardiovascular death remains common in KF, particularly among the dialysis population and in the first few months of treatment. Multi-state models can provide absolute measures of cardiovascular mortality across both dialysis and transplant states., (© 2022 The Authors. Nephrology published by John Wiley & Sons Australia, Ltd on behalf of Asian Pacific Society of Nephrology.)

Purpose: To examine individual retinal layers' location-specific patterns of thicknesses in intermediate age-related macular degeneration (iAMD) using optical coherence tomography (OCT)., Methods: OCT macular cube scans were retrospectively acquired from 84 iAMD eyes of 84 participants and 84 normal eyes of 84 participants propensity-score matched on age, sex, and spherical equivalent refraction. Thicknesses of the retinal nerve fiber layer (RNFL), ganglion cell layer (GCL), inner plexiform layer (IPL), inner nuclear layer (INL), outer plexiform layer (OPL), outer nuclear layer + Henle's fiber layer (ONL+HFL), inner- and outer-segment layers (IS/OS), and retinal pigment epithelium to Bruch's membrane (RPE-BM) were calculated across an 8 × 8 grid (total 24° × 24° area). Location-specific analysis was performed using cluster(normal) and grid(iAMD)-to-cluster(normal) comparisons., Results: In iAMD versus normal eyes, the central RPE-BM was thickened (mean difference ± SEM up to 27.45% ± 7.48%, P < 0.001; up to 7.6 SD-from-normal), whereas there was thinned outer (OPL, ONL+HFL, and non-central RPE-BM, up to -6.76% ± 2.47%, P < 0.001; up to -1.6 SD-from-normal) and inner retina (GCL and IPL, up to -4.83% ± 1.56%, P < 0.01; up to -1.7 SD-from-normal) with eccentricity-based effects. Interlayer correlations were greater against the ONL+HFL (mean |r| ± SEM 0.19 ± 0.03, P = 0.14 to < 0.0001) than the RPE-BM (0.09 ± 0, P = 0.72 to < 0.0001)., Conclusions: Location-specific analysis suggests altered retinal anatomy between iAMD and normal eyes. These data could direct clinical diagnosis and monitoring of AMD toward targeted locations.

Objectives: Many chronic eye conditions are managed within public hospital ophthalmology clinics resulting in encumbered wait lists. Integrated care schemes can increase system capacity. In order to direct implementation of a public hospital-based integrated eye care model, this study aims to evaluate the quality of referrals for new patients through information content, assess triage decisions of newly referred patients and evaluate the consistency of referral content for new patients referred multiple times., Design: A retrospective and prospective review of all referral forms for new patients referred to a public hospital ophthalmology clinic between January 2016 and September 2017, and September 2017 and August 2018, respectively., Setting: A referral-only public hospital ophthalmology clinic in metropolitan Sydney, Australia., Participants: 418 new patients on existing non-urgent wait lists waiting to be allocated an initial appointment, and 528 patients who were newly referred., Primary and Secondary Outcome Measures: The primary outcome was the information content of referrals for new patients. The secondary outcomes were triage outcomes for new incoming referrals, and the number of new patients with multiple referrals., Results: Of the wait-listed referrals, 0.2% were complete in referral content compared with 9.8% of new incoming referrals (p<0.001). Of new incoming referrals, 56.7% were triaged to a non-urgent clinic. Multiple referrals were received for 49 patients, with no change in the amount of referral content., Conclusions: Most referrals were incomplete in content, leading to triage based on limited clinical information. Some new patients were referred multiple times with their second referral containing a similar amount of content as their first. Lengthy wait lists could be prevented by improving administrative processes and communication between the referral centre and referrers. The future implementation of an integrated eye care model at the study setting could sustainably cut wait lists for patients with chronic eye conditions., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: The Australian Government funded a nationwide diabetic retinopathy screening programme to improve visual outcomes for people with diabetes. This study examined the benefits and barriers of the programme, image interpretation pathways and assessed the characteristics of people who had their fundus photos graded by a telereading service which was available as a part of the programme., Design: Multimethod: survey and retrospective review of referral forms., Setting: Twenty-two primary healthcare facilities from urban, regional, rural and remote areas of Australia, and one telereading service operated by a referral-only eye clinic in metropolitan Sydney, Australia., Participants: Twenty-seven primary healthcare workers out of 110 contacted completed a survey, and 145 patient referrals were reviewed., Results: Manifest qualitative content analysis showed that primary healthcare workers reported that the benefits of the screening programme included improved patient outcomes and increased awareness and knowledge of diabetic retinopathy. Barriers related to staffing issues and limited referral pathways. Image grading was performed by a variety of primary healthcare workers, with one responder indicating the utilisation of a diabetic retinopathy reading service. Of the people with fundus photos graded by the reading service, 26.2% were reported to have diabetes. Overall, 12.3% of eyes were diagnosed with diabetic retinopathy. Photo quality was rated as excellent in 46.2% of photos. Referral to an optometrist for diabetic retinopathy was recommended in 4.1% of cases, and to an ophthalmologist in 6.9% of cases., Conclusions: This nationwide diabetic retinopathy screening programme was perceived to increase access to diabetic retinopathy screening in regional, rural and remote areas of Australia. The telereading service has diagnosed diabetic retinopathy and other ocular pathologies in images it has received. Key barriers, such as access to ophthalmologists and optometrists, must be overcome to improve visual outcomes., Competing Interests: Competing interests: VK and PK hold appointments at Centre for Eye Health. Centre for Eye Health is a member of the consortium delivering the Provision of Eye Health and Equipment Training programme. VK does not have any direct or indirect involvement with the project., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Withdrawal from renal replacement therapy is common in patients with end-stage kidney disease (ESKD), but end-of-life service planning is challenging without population-specific data. We aimed to describe mortality after treatment withdrawal in Australian and New Zealand ESKD patients and evaluate death-certified causes of death., Methods: We performed a retrospective cohort study on incident patients with ESKD in Australia, 1980-2013, and New Zealand, 1988-2012, from the Australian and New Zealand Dialysis and Transplant registry. We estimated mortality rates (by age, sex, calendar year and country) and summarized withdrawal-related deaths within 12 months of treatment modality change. Certified causes of death were ascertained from data linkage with the Australian National Death Index and New Zealand Mortality Collection database., Results: Of 60 823 patients with ESKD, there were 8111 treatment withdrawal deaths and 26 207 other deaths over 381 874 person-years. Withdrawal-related mortality rates were higher in females and older age groups. Rates increased between 1995 and 2013, from 1142 (95% confidence interval 1064-1226) to 2706/100 000 person-years (95% confidence interval 2498-2932), with the greatest increase in 1995-2006. A third of withdrawal deaths occurred within 12 months of treatment modality change. The national death registers reported kidney failure as the underlying cause of death in 20% of withdrawal cases, with other causes including diabetes (21%) and hypertensive disease (7%). Kidney disease was not mentioned for 18% of withdrawal patients., Conclusions: Treatment withdrawal represents 24% of ESKD deaths and has more than doubled in rate since 1988. Population data may supplement, but not replace, clinical data for end-of-life kidney-related service planning., (© The Author(s) 2020. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.)

Significance: This article summarizes the evidence for a higher prevalence of binocular vision dysfunctions in individuals with vision impairment. Assessment for and identification of binocular vision dysfunctions can detect individuals experiencing difficulties in activities including reading, object placement tasks, and mobility.Comprehensive vision assessment in low vision populations is necessary to identify the extent of remaining vision and to enable directed rehabilitation efforts. In patients with vision impairment, little attention is typically paid to assessments of binocular vision, including ocular vergence, stereopsis, and binocular summation characteristics. In addition, binocular measurements of threshold automated visual fields are not routinely performed in clinical practice, leading to an incomplete understanding of individuals' binocular visual field and may affect rehabilitation outcomes.First, this review summarizes the prevalence of dysfunctions in ocular vergence, stereopsis, and binocular summation characteristics across a variety of ocular pathologies causing vision impairment. Second, this review examines the links between clinical measurements of binocular visual functions and outcome measures including quality of life and performance in functional tasks. There is an increased prevalence of dysfunctions in ocular alignment, stereopsis, and binocular summation across low vision cohorts compared with those with normal vision. The identification of binocular vision dysfunctions during routine low vision assessments is especially important in patients experiencing difficulties in activities of daily living, including but not limited to reading, object placement tasks, and mobility. However, further research is required to determine whether addressing the identified deficits in binocular vision in low vision rehabilitative efforts directly impacts patient outcomes., Competing Interests: Conflict of Interest Disclosure: JT, MK, and AL receive salary support from Guide Dogs New South Wales/Australian Capital Territory, and JM is an employee of Guide Dogs New South Wales/Australian Capital Territory. JH and VK are recipients of Australian Government Research Training Program scholarships and PhD scholarships provided by Guide Dogs New South Wales/Australian Capital Territory. Guide Dogs New South Wales/Australian Capital Territory played no role in the conceptualization of this article, and the authors have no proprietary interest in any of the materials mentioned in this article., (Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Optometry.)

Current descriptions of retinal thickness across normal age cohorts are mostly limited to global analyses, thus overlooking spatial variation across the retina and limiting spatial analyses of retinal and optic nerve disease. This retrospective cross-sectional study uses location-specific cluster analysis of 8 × 8 macular average grid-wise thicknesses to quantify topographical patterns and rates of normal, age-related changes in all individual retinal layers of 253 eyes of 253 participants across various age cohorts (n = 23-69 eyes per decade). Most retinal layers had concentric spatial cluster patterns except the retinal nerve fibre layer (RNFL) which displayed a nasal, asymmetric radial pattern. Age-related thickness decline mostly occurred after the late 4th decade, described by quadratic regression models. The ganglion cell layer (GCL), inner plexiform layer (IPL), inner nuclear layer (INL), and outer nuclear layer + Henle's fibre layer (ONL +HFL ) were significantly associated with age (p < 0.0001 to < 0.05), demonstrating similar rates of thickness decline (mean pooled slope =  - 0.07 µm/year), while the IS/OS had lesser mean pooled thickness slopes for all clusters (- 0.04 µm/year). The RNFL, OPL, and RPE exhibited no significant age-related thickness change, and the RNFL were significantly associated with sex. Analysis using spatial clusters compared to the ETDRS sectors revealed more extensive spatial definition and less variability in the former method. These spatially defined, clustered normative data and age-correction functions provide an accessible method of retinal thickness analysis with more spatial detail and less variability than the ETDRS sectors, potentially aiding the diagnosis and monitoring of retinal and optic nerve disease.

Background and Objective: Early diagnosis of PAH is clinically challenging. Patterns of diagnostic delay in Australian and New Zealand PAH populations have not been explored in large-scale studies. We aimed to evaluate the magnitude, risk factors and survival impact of diagnostic delay in Australian and New Zealand PAH patients., Methods: A cohort study of PAH patients from the PHSANZ Registry diagnosed from 2004 to 2017 was performed. Diagnostic interval was the time from symptom onset to diagnostic right heart catheterization as recorded in the registry. Factors associated with diagnostic delay were analysed in a multivariate logistic regression model. Survival rates were compared across patients based on the time to diagnosis using Kaplan-Meier method and Cox regression., Results: A total of 2044 patients were included in analysis. At diagnosis, median age was 58 years (IQR: 43-69), female-to-male ratio was 2.8:1 and majority of patients were in NYHA FC III-IV (82%). Median diagnostic interval was 1.2 years (IQR: 0.6-2.7). Age, CHD-PAH, obstructive sleep apnoea and peripheral vascular disease were independently associated with diagnostic interval of ≥1 year. No improvement in diagnostic interval was seen during the study period. Longer diagnostic interval was associated with decreased 5-year survival., Conclusion: PAH patients experience significant diagnostic interval, which has not improved despite increased community awareness. Age, cardiovascular and respiratory comorbidities are significantly associated with longer time to diagnosis. Mortality rates appear higher in patients who experience longer diagnostic interval., (© 2020 Asian Pacific Society of Respirology.)

Purpose: To evaluate the agreement and accuracy of grading goniophotographs and anterior segment optical coherence tomography (AS-OCT) results for assessment of the anterior chamber angle, and elicit factors driving concordance between perceived grade and ground truth., Methods: Three clinicians evaluated the goniophotographs and AS-OCT results of 75 patients. Graders' impressions of the angle grade, trabecular pigmentation, and iris contour were compared with the ground truth gonioscopic examination result when physically performed by a senior optometrist. Percentage agreement and kappa statistics were calculated. Binary logistic regression was used to elicit factors for accurate grading., Results: Exact angle matches and binary (open or closed) evaluations were above guessing rate for all graders. There was a systematic bias toward underestimating the angle structure across all graders, especially at the superior angle, by approximately 1 ordinal unit. Kappa statistics showed fair-moderate agreement for exact (0.387-0.520) and binary (0.347-0.520) angle evaluations. Agreement was unchanged when using a multimodal approach (0.373-0.523). Factors driving concordance were primarily related to the extremes of the anterior chamber angle configuration (shallow or deep structures, and iris contour). However, prediction models did not fully explain the levels of concordance with the ground truth (maximum R 2 amongst models 0.177)., Conclusions: Although moderate agreement between graders and ground truth could be obtained under binary evaluations, angle grades were generally underestimated. Factors affecting concordance were primarily the extremes of the ground truth angle and iris contour., Translational Relevance: We highlight factors affecting accuracy of grading goniophotography and AS-OCT images of the anterior chamber angle., (Copyright 2019 The Authors.)