Ophthalmology (Eye & Ear Hospital) - Research Publications

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    Choroidal Thickening During Young Adulthood and Baseline Choroidal Thickness Predicts Refractive Error Change.
    Lee, SS-Y ; Alonso-Caneiro, D ; Lingham, G ; Chen, FK ; Sanfilippo, PG ; Yazar, S ; Mackey, DA (Association for Research in Vision and Ophthalmology (ARVO), 2022-05-02)
    Purpose: The purpose of this study was to explore the age-related change in choroidal thickness (ChT) and test the hypothesis that baseline ChT is predictive of refractive error change in healthy young adults. Methods: Participants underwent spectral-domain optical coherence tomography (SD-OCT) imaging and autorefraction at 20 (baseline) and 28 years old. The enhanced depth imaging mode on the SD-OCT was used to obtain images of the choroid. Scans were exported from the SD-OCT and analyzed with a custom software that automatically measures the central ChT. The longitudinal change in subfoveal ChT and association between baseline subfoveal ChT and 8-year change in refractive error (spherical equivalent) were determined using linear mixed models. Results: In total, 395 eyes of 198 participants (44% men; 18-22 years at baseline) were included. Over 8 years, mean spherical equivalent decreased by 0.25 diopters (D) and axial length increased by 0.09 mm. Subfoveal choroid thickened by 1.3 µm/year (95% confidence interval [CI] = 0.6-2.0), but this was reduced by 0.9 µm/year (95% CI = 1.6-0.2) for every 1 mm increase in axial length. For every 10 µm increase in baseline ChT, average annual change in spherical equivalent and axial length reduced by 0.006 D/year and 0.003 mm/year, respectively. Conclusions: In a community-based cohort of young adults, the choroid continued to change during early adulthood. Choroidal thickening was less in eyes that were longer at baseline, and the choroid thinned in eyes that showed myopia progression. The association between baseline ChT and longitudinal changes in spherical equivalent and axial length supports the hypothesis that ChT may be predictive of refractive error development and/or myopia progression.
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    Comparison of Anterior Segment Abnormalities in Individuals With FOXC1 and PITX2 Variants
    Prem Senthil, M ; Knight, LSW ; Taranath, D ; Mackey, DA ; Ruddle, JB ; Chiang, MY ; Siggs, OM ; Souzeau, E ; Craig, JE (LIPPINCOTT WILLIAMS & WILKINS, 2022-08-01)
    PURPOSE: Axenfeld-Rieger syndrome encompasses a group of developmental disorders affecting the anterior chamber structures of the eye, with associated systemic features in some cases. This study aims to compare the difference in anterior segment phenotypes such as those involving the cornea, iris, lens, and anterior chamber angle between cases with disease-causing sequence variations in FOXC1 and PITX2 . METHODS: This cross-sectional study involved 61 individuals, from 32 families with pathogenic FOXC1 or PITX2 variants, who were registered with the Australian and New Zealand Registry of Advanced Glaucoma. RESULTS: The median age of the cohort was 39 years at the time of last assessment (range 3-85 years; females, 54%). Thirty-two patients had pathogenic variants in the FOXC1 gene, and 29 patients had pathogenic variants in the PITX2 gene. Corneal abnormalities were more common in individuals with FOXC1 variants (18/36, 50%) than those with PITX2 variants (4/25, 16%; P = 0.007). Iris abnormalities such as hypoplasia ( P = 0.008) and pseudopolycoria ( P = 0.001) were more common in individuals with PITX2 variants than those with FOXC1 variants. Glaucoma was present in 72% of participants. Corneal decompensation was positively associated with corneal abnormalities ( P < 0.001), glaucoma surgery ( P = 0.025), and cataract surgery ( P = 0.002). CONCLUSIONS: Corneal abnormalities were more common in individuals with FOXC1 than in those with PITX2 variants and were often associated with early onset glaucoma. These findings highlight that patients with FOXC1 variations require close follow-up and monitoring throughout infancy and into adulthood.
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    Prevalence of Toxoplasmic Retinochoroiditis in an Australian Adult Population: A Community-Based Study.
    Ferreira, LB ; Furtado, JM ; Charng, J ; Franchina, M ; Matthews, JM ; Molan, AAL ; Hunter, M ; Mackey, DA ; Smith, JR (Elsevier BV, 2022-05-11)
    PURPOSE: Toxoplasmic retinochoroiditis is the most common clinical manifestation of an infection with the protozoan parasite, Toxoplasma gondii. Up to 50% of the human population is estimated to be infected with T. gondii; however, the epidemiology of toxoplasmic retinochoroiditis has not been widely reported. We sought to estimate the prevalence of toxoplasmic retinochoroiditis in Australia using data that were collected as part of the Busselton Healthy Ageing Study. DESIGN: Cross-sectional, community-based, prospective cohort study. PARTICIPANTS: 5020 Australian adults (2264 men and 2756 women; age range, 45-69 years, and median age, 58 years). METHODS: Retinal color photographs, centered on the optic disc and macula, were captured using a digital retinal camera after the dilation of the pupils. Three uveitis-subspecialized ophthalmologists assessed each pigmented retinal lesion, and complete concordance of opinion was required to assign a toxoplasmic etiology. Serum T. gondii immunoglobulin (Ig)G levels were measured for those participants with retinal lesions judged to be toxoplasmic retinochoroiditis. MAIN OUTCOME MEASURES: Prevalence of toxoplasmic retinochoroiditis. RESULTS: Eight participants (0.16%) had retinal lesions that were considered to have the characteristic appearance of toxoplasmic retinochoroiditis, plus detectable serum T. gondii IgG, consistent with the diagnosis of toxoplasmic retinochoroiditis. On the assumption that 23.81% of retinal lesions occur at the posterior pole, as reported in a community-based survey conducted in Brazil (Sci Rep. 2021;11:3420), the prevalence of toxoplasmic retinochoroiditis was estimated to be 0.67% or 1 per 149 persons. CONCLUSIONS: Toxoplasmic retinochoroiditis is common in Australian adults. Efforts to quantify and address risk factors for human infection with T. gondii are justified.
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    Impact of Reference Center Choice on Adaptive Optics Imaging Cone Mosaic Analysis.
    Roshandel, D ; Sampson, DM ; Mackey, DA ; Chen, FK (Association for Research in Vision and Ophthalmology (ARVO), 2022-04-01)
    Purpose: Foveal center marking is a key step in retinal image analysis. We investigated the discordance between the adaptive optics (AO) montage center (AMC) and the foveal pit center (FPC) and its implications for cone mosaic analysis using a commercial flood-illumination AO camera. Methods: Thirty eyes of 30 individuals (including 15 healthy and 15 patients with rod-cone dystrophy) were included. Spectral-domain optical coherence tomography was used to determine the FPC, and flood-illumination AO imaging was performed with overlapping image frames to create an AO montage. The AMC was determined by averaging the (0,0) coordinates in the four paracentral overlapping AO image frames. Cone mosaic measurements at various retinal eccentricities were compared between corresponding retinal loci relative to the AMC or FPC. Results: AMCs were located temporally to the FPCs in 14 of 15 eyes in both groups. The average AMC-FPC discordance was 0.85° among healthy controls and 0.33° among patients with rod-cone dystrophy (P < 0.05). The distance of the AMC from the FPC was a significant determinant of the cone density (β estimate = 218 cells/deg2/deg; 95% confidence interval [CI], 107-330; P < 0.001) and inter-cone distance (β estimate = 0.28 arcmin/deg; 95% CI, 0.15-0.40; P < 0.001), after adjustment for age, sex, axial length, spherical equivalent, eccentricity, and disease status. Conclusions: There is a marked mismatch between the AMC and FPC in healthy eyes that may be modified by disease process such as rod-cone dystrophy. We recommend users of AO imaging systems carefully align the AO montage with a foveal anatomical landmark, such as the FPC, to ensure precise and reproducible localization of the eccentricities and regions of interest for cone mosaic analysis.
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    Incidence of Newly Registered Blindness From Age-Related Macular Degeneration in Australia Over a 21-Year Period: 1996-2016
    Heath Jeffery, RC ; Mukhtar, SA ; Lopez, D ; Preen, DB ; McAllister, IL ; Mackey, DA ; Morlet, N ; Morgan, WH ; Chen, FK (ASIA-PACIFIC ACAD OPHTHALMOLOGY-APAO, 2021-09-01)
    PURPOSE: Report the age-standardized annual incidence of blindness registration due to age-related macular degeneration (AMD) in Australia in patients aged 50 years and older. Frequencies of photodynamic therapy (PDT) and intravitreal therapy (IVT) were examined. DESIGN: Retrospective observational study. SETTING: Registry of the Association for the Blind of Western Australia with best-corrected visual acuity worse than 20/200 in the better-seeing eye. PARTICIPANTS: Registering as blind aged 50 years or over. MEASURES: Annual age-standardized incidence of blindness over 3 time periods: 1996-2001 (pre-PDT), 2002-2007 (PDT era) and 2008-2016 (IVT era). The rates of PDT and IVT usage were assessed. RESULTS: Age-standardized annual incidence of blindness rose during the PDT era, reaching 72.5 cases per 100,000 person-years in 2004. The incidence declined from 2007 onwards, reaching 8.2 cases per 100,000 person-years in 2016 (IVT era). The age at AMD blindness registration increased from 82.7 to 84.9 and 83.7 to 86.0 years from the PDT era to the IVT era in both male and females (P < 0.001) respectively. Over the same time period, PDT usage increased in 2002 and declined in 2006, whereas IVT usage increased from 2009 by 3745 per year. CONCLUSION: The increase in new blindness registrations due to AMD coincided with public funding of verteporfin for PDT, whereas the subsequent decline occurred when bevacizumab was used off-label and ranibizumab and aflibercept were publicly funded. An understanding of the effect of retinal therapy on public health measures may inform improvements in the allocation of limited resources.
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    Attitudes Towards Polygenic Risk Testing in Individuals with Glaucoma
    Hollitt, GL ; Siggs, OM ; Ridge, B ; Keane, MC ; Mackey, DA ; MacGregor, S ; Hewitt, AW ; Craig, JE ; Souzeau, E (ELSEVIER SCIENCE INC, 2022-09-01)
    PURPOSE: Glaucoma is the leading cause of irreversible blindness worldwide; however, vision loss resulting from glaucoma generally can be prevented through early identification and timely implementation of treatment. Recently, polygenic risk scores (PRSs) have shown promise in stratifying individual risk and prognostication for primary open-angle glaucoma (POAG) to reduce disease burden. Integrating PRS testing into clinical practice is becoming increasingly realistic; however, little is known about the attitudes of patients toward such testing. DESIGN: Cross-sectional, questionnaire-based study. PARTICIPANTS: Among the participants in the Australian and New Zealand Registry of Advanced Glaucoma, 2369 were invited to participate who fit the inclusion criteria of adults with a diagnosis of POAG who had not received genetic results that explain their condition, were not known to be deceased, resided in Australia, and had agreed to receive correspondence. METHODS: One thousand one hundred sixty-nine individuals (response rate, 49%) with POAG completed the survey evaluating their attitudes towards polygenic risk testing for glaucoma. MAIN OUTCOME MEASURES: Sociodemographic, health, perception, and emotional factors were examined to assess associations with interest in PRS testing. Interest in PRS testing was evaluated through assessing likelihood to take the test to predict personal risk of disease and disease severity, and whether the individual would recommend the test to family members or others. RESULTS: Our results show strong interest in the test, with 69.4% of individuals (798 of 1150) indicating a keenness in testing before diagnosis, had it been available. In particular, interest was seen in those from an urban area (odds ratio [OR], 1.70; 95% confidence interval [CI], 1.15-2.49; P = 0.007), those who perceived their risk of developing glaucoma as higher (OR, 2.05; 95% CI, 1.28-3.29; P = 0.003), and those who were worried about developing glaucoma (OR, 2.07; 95% CI, 1.27-3.37; P = 0.004). People who were interested in testing were more likely to change their eye health-seeking intentions and to recommend testing to family members and others, as well as to undergo testing for prognostication. CONCLUSIONS: These findings will help to facilitate the clinical implementation of PRS testing for glaucoma to reduce irreversible vision loss.
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    Evaluating Distribution of Foveal Avascular Zone Parameters Corrected by Lateral Magnification and Their Associations with Retinal Thickness
    Li, Q ; Gong, P ; Ho, PH ; Kennedy, BF ; Mackey, DA ; Chen, FK ; Charng, J (Elsevier BV, 2022-06)
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    Prevalence and Risk Factors of Myopia in Young Adults: Review of Findings From the Raine Study.
    Lee, SS-Y ; Mackey, DA (Frontiers Media SA, 2022)
    Myopia tends to develop and progress fastest during childhood, and the age of stabilization has been reported to be 15-16 years old. Thus, most studies on myopia have centered on children. Data on the refractive error profile in young adulthood - a time in life when myopia is thought to have stabilized and refractive error is unaffected by age-related pathology such as cataract - are limited. The Raine Study has been following a community-based cohort of young adults representative of the general Western Australia population since their prenatal periods in 1989-1991, with eye examinations performed when participants were 20 and 28 years old. At 20 years old, prevalence of myopia in the cohort was 25.8%. Using long-term trajectory of serum vitamin D levels and conjunctival ultraviolet autofluorescence (CUVAF) area to objectively quantify sun exposure, the Raine Study confirmed a negative relationship between time spent outdoors and myopia prevalence. However, prospective studies are required to determine the amount of CUVAF area or serum vitamin D levels associated with time duration. Combining data from the Raine Study and several other cohorts, Mendelian randomization studies have confirmed a link between myopia and a genetic predisposition toward higher education. Several novel potential associations of myopia or ocular biometry were investigated, including fetal growth trajectory, which was found to be significantly associated with corneal curvature at 20 years. By age 28, myopia prevalence had increased to 33.2%. Between 20 and 28 years old, myopia progressed and axial length elongated, on average, by -0.041D/year and 0.02 mm/year, respectively. Smaller CUVAF area at follow-up, female sex, and parental myopia were significant risk factors for myopia incidence and progression between 20 and 28 years. Given the limited research in young adults, further investigations are warranted to confirm the Raine Study findings, as well as identify novel genetic or environmental factors of myopia incidence and progression in this age group.
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    Sleep and eye disease: A review
    Lee, SSY ; Nilagiri, VK ; Mackey, DA (WILEY, 2022-03-16)
    There is a growing body of literature on the effects of sleep disorders, in particular obstructive sleep apnoea (OSA), on ocular health, with consistent evidence of an increased risk of floppy eyelid syndrome, non-arteritic anterior ischaemic optic neuropathy, diabetic macular oedema, and other retinal vasculature changes in individuals with OSA. However, reports on OSA's associations with glaucoma, papilloedema, diabetic retinopathy, central serous chorioretinopathy, and keratoconus have been conflicting, while links between OSA and age-related macular degeneration have only been described fairly recently. Despite numerous suggestions that OSA treatment may reduce risk of these eye diseases, well-designed studies to support these claims are lacking. In particular, the ocular hypertensive effects of continuous positive airway pressure (CPAP) therapy for OSA requires further investigation into its potential impact on glaucoma risk and management. Reports of ocular surface complications secondary to leaking CPAP masks highlights the importance of ensuring good mask fit. Poor sleep habits have also been linked with increased myopia risk; however, the evidence on this association remains weak.