Ophthalmology (Eye & Ear Hospital) - Research Publications
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ItemCorrelation Between Macular Integrity Assessment and Optical Coherence Tomography Imaging of Ellipsoid Zone in Macular Telangiectasia Type 2(ASSOC RESEARCH VISION OPHTHALMOLOGY INC, 2017-05)PURPOSE: To correlate ellipsoid zone (EZ) defects on spectral-domain optical coherence tomography (SD-OCT) with retinal sensitivity loss on macular integrity assessment (MAIA) microperimetry in macular telangiectasia type 2 (MacTel). METHODS: Macular SD-OCT volumes and microperimetry maps were obtained during the international, multicenter, randomized phase 2 trial of ciliary neurotrophic factor for type 2 MacTel on two visits within 5 days of one another. Software was developed to register SD-OCT to MAIA scanning laser ophthalmoscopy images and to overlay EZ defect areas on the microperimetry maps generated from microperimetry sensitivity values at specific points and from interpolated sensitivity values. A total of 134 eyes of 67 patients were investigated. RESULTS: The semiautomated registration algorithm was found to be accurate, both qualitatively by visual inspection of the nearly perfect overlap of the retinal vessels and quantitatively as assessed by interobserver reliability metrics performed in 98 eyes of 49 patients (intraclass correlation of aggregate retinal sensitivity loss >0.99). Aggregate retinal sensitivity loss within the EZ defect area was highly correlated with EZ defect area (Pearson correlation coefficient 0.93 and 0.92 at screening and baseline for noninterpolated maps; both were 0.94 for interpolated maps; P values <0.001). CONCLUSIONS: With our software and image processing algorithms, there is nearly perfect correlation between retinal sensitivity on microperimetry and EZ defect area on SD-OCT. Our software allows determination of functional and structural changes with increasing disease severity and demonstrates that functional loss on microperimetry may be used as a surrogate marker of EZ loss on SD-OCT in type 2 MacTel.
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ItemGaming to improve vision: 21st century self-monitoring for patients with age-related macular degeneration(WILEY, 2018-07)IMPORTANCE: Improved vision self-monitoring tools are required for people at risk of neovascular complications from age related macular degeneration (AMD). BACKGROUND: to report the self-monitoring habits of participants with intermediate AMD using the Amsler grid chart, and the use of personal electronic devices and gameplay in this over 50 year old cohort. DESIGN: single-centre descriptive study carried out at the Centre for Eye Research (CERA), Melbourne, Australia. PARTICIPANTS: 140 participants over 50 years of age, with a diagnosis of intermediate AMD and best-corrected visual acuity (BCVA) of ≥6/12 in each eye. METHODS: structured questionnaire survey of participants who were enrolled in natural history of AMD studies at CERA. MAIN OUTCOME MEASURES: frequency of vision self-monitoring using the Amsler grid chart, and frequency of general use of personal electronic devices and gameplay. RESULTS: Of 140 participants with mean age of 70.5 years, 83.6% used an Amsler grid chart, but only 39.3% used it once per week. Most participants (91.4%) used one or more personal electronic devices. Of these, over half (54.7%) played games on them, among whom 39% played games once a day. Of participants aged 50-69 years, 92% (95%CI 85.1-98.9) were willing to play a game to monitor their vision, compared to 78% (95%CI 69.0-87.0) of those aged 70 years and older (P < 0.05). CONCLUSIONS AND RELEVANCE: a large proportion of AMD patients already use personal electronic devices. Gamification techniques are likely to increase compliance with self-monitoring, leading to earlier detection in the next generation of patients with neovascular AMD.
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ItemClinical and social characteristics associated with reduced visual acuity at presentation in Australian patients with neovascular age-related macular degeneration: a prospective study from a long-term observational data set. The Fight Retinal Blindness! Project(WILEY, 2018-04)IMPORTANCE: Identifying variables that influence presenting visual acuity (VA) in patients with neovascular age-related macular degeneration (nAMD) is important because it is a strong predictor of long-term outcomes. BACKGROUND: To assess the clinical and social characteristics associated with low presenting VA in nAMD patients. DESIGN: The present study is a cross-sectional analysis from a prospective, observational database. PARTICIPANTS: We identified 3242 treatment-naïve patients from 54 Australian practices in the Fight Retinal Blindness! registry. METHODS: Age, gender, ethnicity and VA were recorded at the baseline visit. Socio-economic status was determined using the Australian Bureau of Statistics socio-economic indexes for areas. MAIN OUTCOME MEASURES: Association between clinical and socio-economic characteristics with presenting VA was identified. RESULTS: Poor VA (≤35 letters) in the presenting eye was associated with older age (adjusted odds ratio [AOR]: 1.33 for patients aged ≥80 years vs. <80 years [95% confidence interval, CI: 1.04, 1.71]), treatment at a public practice (AOR: 1.91 for public vs. private practices [95% CI: 1.46, 2.50]) and intermediate (36-69 letters) VA in the fellow eye (AOR: 0.67 [95% CI: 0.47, 0.95] and 0.64 [95% CI: 0.48, 0.85] for poor [≤35 letters] and good [≥70 letters] VA vs. intermediate VA in the fellow eye). Gender, ethnicity and socio-economic status were not independently associated with VA at presentation. CONCLUSIONS AND RELEVANCE: Poor presenting vision is detrimental to the long-term outcomes of nAMD. Poor presentation of nAMD in Australia may not be related to socio-economic circumstances, but due to systems of care. Further research is warranted to determine why patients at public practices present with worse vision compared with private practices in Australia.
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ItemDisparities in access to anti-vascular endothelial growth factor treatment for neovascular age-related macular degeneration(WILEY, 2017-03)BACKGROUND: Late neovascular age-related macular degeneration (nvAMD) is very common and causes irreversible severe visual loss unless treated swiftly with vascular endothelial growth factor (VEGF) inhibitors. Although publicly subsidized access to treatment may be inequitable, which is why we assessed treatment provision across Australia. DESIGN: Secondary analysis of Australian data. PARTICIPANTS: All Pharmaceutical Benefits Scheme (including Repatriation PBS) beneficiaries. METHODS: Treatment and incidence data were obtained from Medicare Australia, the Royal Australian and New Zealand College of Ophthalmologists, Optometry Australia, the Blue Mountains Eye Study and the Australian Bureau of Statistics. Data were mapped using geographical information software, and factors associated with treatment provision were assessed using multiple linear regression models. MAIN OUTCOME MEASURE: Unmet need (%) for anti-VEGF treatment for nvAMD. RESULTS: On average, we estimated 7316 incident cases of nvAMD not to be treated per year from 2010 to 2014 (50.1% of total). Number of ophthalmologists and optometrists (per 1000, β = -0.024; 95% confidence interval [CI] -0.041, -0.007) and being located in remote regions (β = 0.186; 95% CI 0.110, 0.262) were associated with percentage of untreated cases. A higher proportion of the population speaking a language other than English at home was associated in univariate analyses only (β = 0.0015; 95% CI -0.0004, 0.0027; P = 0.007). CONCLUSION: A large proportion of incident nvAMD is not treated with anti-VEGF. Not receiving treatment is more likely in regional or remote areas and areas with fewer service providers. Not speaking English at home may further limit access. Service delivery models for more equitable service provision are needed.
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ItemEllipsoid zone on optical coherence tomography: a review(WILEY, 2016-07)Emergence of the high-resolution optical coherence tomography has allowed better delineation of retinal layers, and many of the anatomical correlations of these layers have now been agreed upon. However, some anatomical correlates still remain contentious, such as the second hyper-reflective band, which is now termed ellipsoid zone. Despite the lack of consensus of the actual origin of the ellipsoid zone, there has been much interest in evaluating its integrity and intensity in different disease processes. This review paper aims to provide an overview of the ellipsoid zone and its clinical and research applications.
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ItemCorrelation of Histologic Features with In Vivo Imaging of Reticular Pseudodrusen(ELSEVIER SCIENCE INC, 2016-06)PURPOSE: To determine the histologic and cellular correlates in the retina and retinal pigment epithelium (RPE) with the presence of optical coherence tomography-defined reticular pseudodrusen (RPD). DESIGN: Observation case using immunocytochemistry of an exenterated eye with immediate fixation after removal. PARTICIPANTS: Two patients, one with confirmed RPD and the other with mid-peripheral drusen, underwent multimethod imaging before exenteration and immediate fixation of the posterior eyecup for high-resolution immunocytochemical analysis. METHODS: Optical coherence tomography (OCT) was compared with high-resolution immunocytochemistry using a range of cellular markers to determine changes in the RPE, photoreceptors, and gliosis. MAIN OUTCOME MEASURES: Correlations of the appearance of reticular pseudodrusen on OCT and immunocytochemical analysis. RESULTS: Reticular pseudodrusen were deposits juxtaposed to photoreceptor outer segments extending through the outer nuclear layer and even beyond the outer limiting membrane. Deposits were rich in vitronectin, photoreceptor-associated proteins, and Iba1-immunoreactive immune cells. In contrast to conventional drusen the lipid stain Oil Red O failed to stain RPD. Cellular analysis revealed that RPD were associated with photoreceptor disruption and loss and localized gliosis. In addition, anomalies in the RPE were observed. CONCLUSIONS: Reticular pseudodrusen represent subretinal deposits that extend through the outer nuclear layer, affect photoreceptor integrity, and are associated with retinal gliosis and RPE damage.
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ItemNanosecond Laser Treatment for Age-Related Macular Degeneration Does Not Induce Focal Vision Loss or New Vessel Growth in the Retina(ASSOC RESEARCH VISION OPHTHALMOLOGY INC, 2018-02)PURPOSE: Subthreshold, nanosecond pulsed laser treatment shows promise as a treatment for age-related macular degeneration (AMD); however, the safety profile needs to be robustly examined. The aim of this study was to investigate the effects of laser treatment in humans and mice. METHODS: Patients with AMD were treated with nanosecond pulsed laser at subthreshold (no visible retinal effect) energy doses (0.15-0.45 mJ) and retinal sensitivity was assessed with microperimetry. Adult C57BL6J mice were treated at subthreshold (0.065 mJ) and suprathreshold (photoreceptor loss, 0.5 mJ) energy settings. The retinal and vascular responses were analyzed by fundus imaging, histologic assessment, and quantitative PCR. RESULTS: Microperimetry analysis showed laser treatment had no effect on retinal sensitivity under treated areas in patients 6 months to 7 years after treatment. In mice, subthreshold laser treatment induced RPE loss at 5 hours, and by 7 days the RPE had retiled. Fundus imaging showed reduced RPE pigmentation but no change in retinal thickness up to 3 months. Electron microscopy revealed changes in melanosomes in the RPE, but Bruch's membrane was intact across the laser regions. Histologic analysis showed normal vasculature and no neovascularization. Suprathreshold laser treatment did not induce changes in angiogenic genes associated with neovascularization. Instead pigment epithelium-derived factor, an antiangiogenic factor, was upregulated. CONCLUSIONS: In humans, low-energy, nanosecond pulsed laser treatment is not damaging to local retinal sensitivity. In mice, treatment does not damage Bruch's membrane or induce neovascularization, highlighting a reduced side effect profile of this nanosecond laser when used in a subthreshold manner.
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ItemDevelopment and validation of a deep-learning algorithm for the detection of neovascular age-related macular degeneration from colour fundus photographs(WILEY, 2019-11)IMPORTANCE: Detection of early onset neovascular age-related macular degeneration (AMD) is critical to protecting vision. BACKGROUND: To describe the development and validation of a deep-learning algorithm (DLA) for the detection of neovascular age-related macular degeneration. DESIGN: Development and validation of a DLA using retrospective datasets. PARTICIPANTS: We developed and trained the DLA using 56 113 retinal images and an additional 86 162 images from an independent dataset to externally validate the DLA. All images were non-stereoscopic and retrospectively collected. METHODS: The internal validation dataset was derived from real-world clinical settings in China. Gold standard grading was assigned when consensus was reached by three individual ophthalmologists. The DLA classified 31 247 images as gradable and 24 866 as ungradable (poor quality or poor field definition). These ungradable images were used to create a classification model for image quality. Efficiency and diagnostic accuracy were tested using 86 162 images derived from the Melbourne Collaborative Cohort Study. Neovascular AMD and/or ungradable outcome in one or both eyes was considered referable. MAIN OUTCOME MEASURES: Area under the receiver operating characteristic curve (AUC), sensitivity and specificity. RESULTS: In the internal validation dataset, the AUC, sensitivity and specificity of the DLA for neovascular AMD was 0.995, 96.7%, 96.4%, respectively. Testing against the independent external dataset achieved an AUC, sensitivity and specificity of 0.967, 100% and 93.4%, respectively. More than 60% of false positive cases displayed other macular pathologies. Amongst the false negative cases (internal validation dataset only), over half (57.2%) proved to be undetected detachment of the neurosensory retina or RPE layer. CONCLUSIONS AND RELEVANCE: This DLA shows robust performance for the detection of neovascular AMD amongst retinal images from a multi-ethnic sample and under different imaging protocols. Further research is warranted to investigate where this technology could be best utilized within screening and research settings.
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ItemProgression characteristics of ellipsoid zone loss in macular telangiectasia type 2(WILEY, 2019-11)PURPOSE: To investigate the progression characteristics of ellipsoid zone (EZ) loss in eyes with macular telangiectasia type 2 (MacTel) as reflected by area and linear measurements, and their relevance for visual acuity. METHODS: Participants were selected from the MacTel Study cohort. Linear and area measurements of EZ loss were performed in Spectral-Domain Optical Coherence Tomograph (SD-OCT) volume scans. Progression characteristics and correlations between linear and area measurements were analysed using linear mixed effects models. RESULTS: A total of 134 eyes of 70 patients were included (85 eyes with follow-up, mean 4.7 years, range: 1.4-8 years). Ellipsoid zone (EZ) loss significantly progressed at a mean annual increment of 0.057 mm2 (p = 0.005). The progression rate was non-linear and interacted significantly with initial EZ lesion size indicating an exponential growth before reaching a plateau. There was a strong heterogeneity in area sizes between fellow eyes. EZ break length had a significant linear effect on EZ break area (b = 1.06, p < 0.001) and could predict it. The location of the EZ break had a significant impact on visual acuity. CONCLUSION: Ellipsoid zone (EZ) loss in MacTel has a non-linear progression characteristic, and its rate depends on area size at baseline, which must be taken into account at sample selection in clinical trials. Our results show a good correlation of linear and area measures of EZ loss and a segregation of best-corrected visual acuity by EZ location, which may help routine clinical practice.
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