Publications by authors named "Ashish Agar"

63 Publications

Irritable bowel syndrome and risk of glaucoma: An analysis of two independent population-based cohort studies.

United European Gastroenterol J 2021 Aug 25. Epub 2021 Aug 25.

School of Medicine and Public Health, The Centre for Clinical Epidemiology and Biostatistics, The Australian GastroIntestinal Research Alliance (AGIRA), The University of Newcastle, Callaghan, New South Wales, Australia.

Objective: Irritable bowel syndrome (IBS) is a chronic disorder associated with an abnormal gastrointestinal microbiome. Microbiome-host interactions are known to influence organ function including in the central nervous system; thus, we sought to identify whether IBS may be a risk factor for the development of glaucoma.

Design: Two prospective cohort studies.

Subjects: The 1958 United Kingdom Birth Cohort (UKBC; 9091 individuals) and the Danish National Registry of Patients (DNRP; 62,541 individuals with IBS and 625,410 matched general population cohort members).

Methods: In the UKBC, participants were surveyed throughout life (including at ages 42 and 50). The DNRP contains records of hospital-based contacts and prescription data from the national prescription database.

Main Outcome Measure: The main outcome measure was incidence of glaucoma. In the UKBC, incident glaucoma at age 50 (n = 48) was determined through comparison of survey responses at ages 42 and 50 years. In the DNRP, glaucoma was assessed by hospital diagnosis (n = 1510), glaucoma surgery (n = 582) and initiation of glaucoma medications (n = 1674).

Results: In the UKBC, the odds ratio (OR) of developing glaucoma between ages 42 and 50 in persons with a chronic IBS diagnosis was increased [OR: 5.84, 95% confidence interval (CI): 2.26-15.13]. People with an IBS diagnosis in the DNRP had a hazard ratio (HR) of 1.35 for developing physician-diagnosed glaucoma (95% CI: 1.16-1.56), an HR of 1.35 for undergoing glaucoma surgery (95% CI: 1.06-1.70) and an HR of 1.19 for initiating glaucoma medication (95% CI: 1.03-1.38).

Conclusions: In two large European cohort studies, IBS is a risk factor for glaucoma.
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http://dx.doi.org/10.1002/ueg2.12136DOI Listing
August 2021

Evaluation of the initial implementation of a nationwide diabetic retinopathy screening programme in primary care: a multimethod study.

BMJ Open 2021 08 18;11(8):e044805. Epub 2021 Aug 18.

School of Optometry and Vision Science, Faculty of Medicine and Health, University of New South Wales, Sydney, New South Wales, Australia

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.
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http://dx.doi.org/10.1136/bmjopen-2020-044805DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8375720PMC
August 2021

Recovery From Charles Bonnet Syndrome Following Posterior Reversible Encephalopathy Syndrome.

J Neuroophthalmol 2021 Apr 14. Epub 2021 Apr 14.

Faculty of Medicine, University of New South Wales (JJMH, IWJ, MAK, ML, ET, ELSW, LCD, AA, ICF), Kensington, NSW, Australia; Department of Neurology (AS), Northern Beaches Hospital, Sydney, NSW, Australia; Department of Cardiology (AI), Northern Beaches Hospital, Sydney, NSW, Australia; Department of Emergency Medicine (TE), Northern Beaches Hospital, Sydney, NSW, Australia; Department of Radiology (AGP), Northern Beaches Hospital, Sydney, NSW, Australia; Medical Imaging Department (LCD), Prince of Wales Hospital, Randwick, NSW, Australia; Department of Ophthalmology (AA, ICF), Prince of Wales Hospital, Randwick, NSW, Australia; and Department of Ophthalmology (ICF), Northern Beaches Hospital, Sydney, NSW, Australia.

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http://dx.doi.org/10.1097/WNO.0000000000001206DOI Listing
April 2021

Subpalpebral Antibiotic Lavage as Safe, Emergent, and Cost-Effective Management of Acute Infectious Keratitis Related to Contact Lens Overwear: Case Report and Literature Review.

Cornea 2021 Apr 14. Epub 2021 Apr 14.

Faculty of Medicine, University of New South Wales, Sydney, Australia; Royal North Shore Hospital, Sydney, Australia; and Department of Ophthalmology, Prince of Wales Hospital, Sydney, Australia.

Purpose: The aim of this study is to describe the technique of subpalpebral antibiotic lavage (SAL), which is a highly therapeutic, efficient, and cost-effective method for managing severe bacterial keratitis.

Methods: This case report describes a 26-year-old woman with severe bacterial keratitis in the right eye due to contact lens overwear, with progressive corneal thinning, a hypopyon, impending perforation, and marked visual loss to perception of light despite treatment with intensive topical antibiotics. This was managed with SAL that involves the insertion of a cannula transcutaneously into the upper conjunctival fornix to provide continuous antibiotic irrigation of the ocular surface.

Results: By 11 weeks after presentation, the cornea and anterior chamber appeared clinically quiescent, and visual acuity improved to 20/40 corrected in the right eye.

Conclusions: Bacterial keratitis is a potentially blinding condition for which contact lens wear is an important risk factor. Most cases are successfully managed with topical medications; however, in cases of treatment failure, a second-line approach such as SAL can be sight-saving. SAL uses readily available equipment for the delivery of high concentrations of antibiotics to the ocular surface, thus increasing therapeutic efficacy and reducing nursing staff workload. Despite its advantages, the literature reveals apparent underutilization of this technique.
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http://dx.doi.org/10.1097/ICO.0000000000002745DOI Listing
April 2021

Comment on: The Effect of Obstructive Sleep Apnea on Absolute Risk of Central Serous Chorioretinopathy.

Am J Ophthalmol 2021 06 8;226:270-275. Epub 2021 Feb 8.

Faculty of Medicine, University of New South Wales, Sydney, Australia; Department of Ophthalmology, Prince of Wales Hospital, Sydney, Australia.

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http://dx.doi.org/10.1016/j.ajo.2020.12.036DOI Listing
June 2021

A combined convolutional and recurrent neural network for enhanced glaucoma detection.

Sci Rep 2021 01 21;11(1):1945. Epub 2021 Jan 21.

Vision Science Group, Graduate School of Health, University of Technology Sydney, Sydney, Australia.

Glaucoma, a leading cause of blindness, is a multifaceted disease with several patho-physiological features manifesting in single fundus images (e.g., optic nerve cupping) as well as fundus videos (e.g., vascular pulsatility index). Current convolutional neural networks (CNNs) developed to detect glaucoma are all based on spatial features embedded in an image. We developed a combined CNN and recurrent neural network (RNN) that not only extracts the spatial features in a fundus image but also the temporal features embedded in a fundus video (i.e., sequential images). A total of 1810 fundus images and 295 fundus videos were used to train a CNN and a combined CNN and Long Short-Term Memory RNN. The combined CNN/RNN model reached an average F-measure of 96.2% in separating glaucoma from healthy eyes. In contrast, the base CNN model reached an average F-measure of only 79.2%. This proof-of-concept study demonstrates that extracting spatial and temporal features from fundus videos using a combined CNN and RNN, can markedly enhance the accuracy of glaucoma detection.
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http://dx.doi.org/10.1038/s41598-021-81554-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7820237PMC
January 2021

Outcome challenges for cataract surgery employing the New Zealand Cataract Risk Stratification criteria.

Clin Exp Ophthalmol 2021 Jan 10. Epub 2021 Jan 10.

Faculty of Medicine, The University of New South Wales, Sydney, New South Wales, Australia.

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http://dx.doi.org/10.1111/ceo.13882DOI Listing
January 2021

Low-Grade Versus Medium-Grade Nuclear Sclerotic Cataract Density Produces Identical Surgical and Visual Outcomes: A Prospective Single-Surgeon Study.

Cureus 2020 Dec 9;12(12):e11997. Epub 2020 Dec 9.

Department of Ophthalmology, Prince of Wales Hospital, Sydney, AUS.

Purpose To determine whether the incidence of major complications and postoperative corrected distance visual acuity are comparable for surgery on low-grade versus medium-grade nuclear sclerotic cataracts. Design This was a prospective, consecutive, single-surgeon, no-exclusion study of 1025 cataract cases with one-month follow-up. Methods Patients were divided into two cohorts according to the nuclear sclerosis grade at presentation, as classified using the Lens Opacities Classification System (LOCS) III. Cohort A, representing low-grade nuclear sclerotic cataracts (grades 1-2), consisted of 739 eyes, while Cohort B, representing medium-grade nuclear sclerotic cataracts (grades 3-6), consisted of 286 eyes. Results There was no significant difference in major intraoperative or postoperative complications (p>0.999) between Cohorts A and B. The mean logMar preoperative corrected distance visual acuity (CDVA) in Cohort A was 0.245 as compared with 0.346 in Cohort B (p<0.001). There was no significant difference between cohorts for postoperative CDVA at one day (-0.168 versus -0.118; p=0.070), one week (-0.180 versus -0.147; p=0.405), or one month (-0.185 versus -0.161; p=0.569). Conclusions There was no significant difference in the incidence of operative complications or postoperative CDVA between the cohorts. These findings suggest that, in experienced hands, surgery for medium-grade nuclear sclerotic cataracts is equally effective and safe as compared with that for low-grade nuclear sclerotic cataracts.
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http://dx.doi.org/10.7759/cureus.11997DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7793447PMC
December 2020

Curettage for Copious Conjunctival Concretions.

Cureus 2020 Nov 28;12(11):e11742. Epub 2020 Nov 28.

Ophthalmology, Prince of Wales Hospital, Sydney, AUS.

Management of multiple exposed eyelid concretions can be performed successfully in an anesthetized eyelid with gentle curettage of the concretions using a small chalazion curette. It has the advantage of managing the patient supine, providing better eyelid stability and visibility, and minimizing risk in the event of patient movement. This curettage technique was used to facilitate the successful resolution of a patient's ocular surface irritative symptomatology due to multiple exposed concretions.
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http://dx.doi.org/10.7759/cureus.11742DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7773287PMC
November 2020

A Polygenic Risk Score Predicts Intraocular Pressure Readings Outside Office Hours and Early Morning Spikes as Measured by Home Tonometry.

Ophthalmol Glaucoma 2021 Jul-Aug;4(4):411-420. Epub 2020 Dec 11.

Department of Ophthalmology, Flinders University, Flinders Medical Centre, Bedford Park, Australia.

Purpose: Intraocular pressure (IOP) elevations may occur in early morning or outside office hours and can be missed during routine in-clinic IOP measurements. Such fluctuations or peaks likely contribute to glaucoma progression. We sought to investigate the relationship between an IOP polygenic risk score (PRS) and short-term IOP profile.

Design: Cross-sectional study.

Participants: Four hundred seventy-three eyes from 239 participants with suspected or established primary open-angle glaucoma sampled from 4 outpatient clinics in Australia between August 2016 and December 2019.

Methods: Participants underwent Icare HOME (Icare Oy, Vanda, Finland) tonometer measurements to record IOP 4 times daily for 5 days. Unreliable measurements were excluded. A minimum of 2 days with at least 3 reliable measurements were required. We used a validated IOP PRS derived from 146 IOP-associated variants in a linear regression model adjusted for central corneal thickness and age.

Main Outcome Measures: Highest recorded early morning IOP and mean IOP within and outside office hours. Early morning IOP spikes were defined by a higher early morning IOP than the maximum in-office hours IOP.

Results: Reliable measurements were obtained from 334 eyes of 176 participants (mean age, 64 ± 9 years). Eyes in the highest IOP PRS quintile showed an early morning IOP increase of 4.3 mmHg (95% confidence interval [CI], 1.4-7.3; P = 0.005) and mean increase in IOP outside office hours of 2.7 mmHg (95% CI, 0.61-4.7; P = 0.013) than the lowest quintile, which were significant independently after accounting for a recent in-clinic IOP measured by Goldmann applanation tonometry. Eyes in the highest PRS quintile were 5.4-fold more likely to show early morning IOP spikes than the lowest quintile (odds ratio 95% CI, 1.3-23.6; P = 0.023).

Conclusions: A validated IOP PRS was associated with higher early morning IOP and mean IOP outside office hours. These findings support a role for genetic risk prediction of susceptibility to elevated IOP that may not be apparent during in-clinic hours, requiring more detailed clinical phenotyping using home tonometry, the results of which may guide additional interventions to improve IOP control.
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http://dx.doi.org/10.1016/j.ogla.2020.12.002DOI Listing
December 2020

Corneal Stiffness Parameters Are Predictive of Structural and Functional Progression in Glaucoma Suspect Eyes.

Ophthalmology 2021 Jul 25;128(7):993-1004. Epub 2020 Nov 25.

Department of Ophthalmology, Flinders University, Flinders Medical Centre, Bedford Park, Australia.

Purpose: To investigate corneal stiffness parameters (SPs) as predictors of future progression risk in glaucoma suspect eyes.

Design: Prospective, longitudinal study.

Participants: Three hundred seventy-one eyes from 228 primary open-angle glaucoma suspects, based on optic disc appearance, with normal baseline Humphrey Visual Field (HVF; Carl Zeiss Meditec) results.

Methods: Baseline corneal SPs were measured using Corvis ST (Oculus Optikgeräte GmbH). Participants were followed up every 6 months with clinical examination, HVF testing, and OCT. The baseline SP at first applanation (SP-A1) and highest concavity predicted the prospective outcome measures.

Main Outcome Measures: Structural progression was measured by the OCT rate of thinning of the retinal nerve fiber layer (RNFL) and ganglion cell-inner plexiform layer (GCIPL). Functional progression was assessed by permutation analysis of pointwise linear regression criteria on HVF testing.

Results: Stiffness parameters correlated positively with central corneal thickness (CCT), which was adjusted for in all analyses. A higher SP-A1, suggestive of a stiffer cornea, was associated with a faster rate of RNFL thinning (P < 0.001), synergistic with thinner CCT (P = 0.004) over a mean follow-up of 4.2 years. Eyes with higher SP-A1 and thinner CCT (thin and stiff corneas) showed accelerated RNFL thinning by 0.72 μm/year relative to eyes with lower SP-A1 and thicker CCT (95% confidence interval [CI], 0.17-1.28; P = 0.011) and were at 2.9-fold higher likelihood of fast RNFL progression of more than 1 μm/year (95% CI, 1.4-6.1; P = 0.006). Consistent results also were observed with GCIPL thinning. Furthermore, a higher SP-A1 was associated with a greater risk of visual field progression (P = 0.002), synergistic with thinner CCT (P = 0.010). Eyes with higher SP-A1 and thinner CCT were at 3.7-fold greater risk of visual field progression relative to eyes with thicker CCT and lower SP-A1 (95% CI, 1.3-10.5; P = 0.014).

Conclusions: Glaucoma suspect eyes with higher corneal SPs and lower CCT, suggestive of thin and stiff corneas, are at greater risk of progression. Corneal SPs seem to act synergistically with CCT as risk factors for glaucoma progression.
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http://dx.doi.org/10.1016/j.ophtha.2020.11.021DOI Listing
July 2021

Visualizing the Consistency of Clinical Characteristics that Distinguish Healthy Persons, Glaucoma Suspect Patients, and Manifest Glaucoma Patients.

Ophthalmol Glaucoma 2020 Jul - Aug;3(4):274-287. Epub 2020 Apr 26.

Centre for Eye Health, University of New South Wales, Kensington, Australia; School of Optometry and Vision Science, University of New South Wales, Kensington, Australia.

Purpose: To use factor analysis to visualize and assess the reproducibility and consistency of clinical quantitative parameters that can optimally distinguish among healthy, glaucoma suspect, and manifest glaucoma patients at a cross-sectional level and thus to describe the transition of quantitative change among the diagnostic categories.

Design: Retrospective cross-sectional study.

Participants: The medical records of healthy, glaucoma suspect, and manifest glaucoma patients (diagnosed by expert clinicians) seen at the Centre for Eye Health in 2015 (n = 148, n = 664, and n = 129, respectively) and 2018 (n = 242, n = 464, and n = 126, respectively) were reviewed. One eye was selected for the study.

Methods: Quantitative clinical measures (intraocular pressure [IOP], central corneal thickness [CCT], visual field [VF], and OCT) were extracted and binary logistic (backward stepwise) regression was performed to identify factors that dictated separation between diagnostic pairs. These were used systematically as inputs for factor analysis to determine a final model that could potentially predict a clinical diagnosis.

Main Outcome Measures: Intraocular pressure, CCT, VF (mean deviation and pattern standard deviation) indices, and OCT optic nerve head parameters and thickness values (retinal nerve fiber layer [RNFL] and ganglion cell-inner plexiform layer).

Results: Few clinical parameters were identified commonly as significant across all diagnostic pairings for 2015 (3 of 23: IOP, pattern standard deviation, and 7-o'clock RNFL thickness) and 2018 (1 of 23: vertical cup-to-disc ratio). Few parameters overlapped when comparing 2015 and 2018 results, highlighting inconsistencies in the models between years. Factor analysis showed good separation between healthy persons and glaucoma patients. Using biplots to visualize the data in 2-dimensional clusters, glaucoma suspect patients demonstrated substantial overlap with healthy and glaucoma cohorts. The contributions of each parameter to diagnostic separation changed between groups and years.

Conclusions: Despite advances in quantitative ocular imaging and perimetry, the transition among healthy, glaucoma suspect, and manifest glaucoma patients remains confounded by a lack of consistent, reproducible combinations of quantitative clinical criteria. These results highlight the nebulousness (at patient-, instrument-, and clinician-related levels) of glaucoma diagnosis that remains contingent on individual clinical expertise and assessment.
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http://dx.doi.org/10.1016/j.ogla.2020.04.009DOI Listing
September 2021

Assessment of Obstructive Sleep Apnoea and Sleeping Laterality by Evaluating Upper Eyelid Distraction: A Prospective, Comparative Polysomnographic Study.

Cureus 2020 Aug 5;12(8):e9566. Epub 2020 Aug 5.

Ophthalmology, The Prince of Wales Hospital, Sydney, AUS.

Objective Our goal was to evaluate upper eyelid laxity by digital distraction, with the aim to determine sleeping laterality and the likelihood of obstructive sleep apnoea (OSA), and correlate these findings with polysomnography (PSG). Design We conducted a prospective, single-centre multidisciplinary study in a large sleep and respiratory department and an ophthalmology department within a tertiary referral university teaching hospital. Methods Patients with known OSA were evaluated using techniques based on the Lateralising Eyelid Sleep Compression (LESC) study. Upper eyelid laxity was assessed by two masked investigators, and the eyelid side with greater laxity was regarded as indicative of that patient's sleeping laterality: 'investigator-detected sleeping laterality' (ID SL). Each patient was then asked about the laterality of his or her accustomed sleeping position: 'patient-reported sleeping laterality' (PR SL). PSG was conducted according to the standard protocol of the Department of Sleep and Respiratory Medicine (DSRM). 'Polysomnography-detected sleeping laterality' (PSG SL) permitted the extraction of sleep positional data by two masked sleep scientists. Results The reliability of the LESC technique for diagnosing ID SL was demonstrated to be statistically significant (p<0.01). Upper eyelid laxity was significantly greater on the patients' sleeping side (t=6.340, df=45, p<0.01, two-tailed). There was a significant correlation between PR SL and ID SL (r =0.33). However, PSG SL did not correlate with sleeping laterality compared with both ID SL and PR SL. Conclusion This study confirms that there is a statistically significant correlation of sleeping laterality with increasing upper eyelid laxity in OSA. Counterintuitively, PSG SL correlated poorly with ID SL and PR SL. This may likely be explained by the technical limitations implicit in current PSG techniques.
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http://dx.doi.org/10.7759/cureus.9566DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7473605PMC
August 2020

Objective Quantification of Spontaneous Retinal Venous Pulsations Using a Novel Tablet-Based Ophthalmoscope.

Transl Vis Sci Technol 2020 03 18;9(4):19. Epub 2020 Mar 18.

Vision Science Group, Discipline of Orthoptics, Graduate School of Health, University of Technology Sydney, NSW, Australia.

Purpose: Dynamic assessment of retinal vascular characteristics can aid in identifying glaucoma-specific biomarkers. More specifically, a loss of spontaneous retinal venous pulsations (SVPs) has been reported in glaucoma, but a lack of readily available tools has limited the ability to explore the full potential of SVP analysis in glaucoma assessment. Advancements in smart technology have paved the way for the development of portable, noninvasive, and inexpensive imaging modalities. By combining off-the-shelf optical elements and smart devices, the current study aims to determine whether SVPs can be detected and quantified using a novel tablet-based ophthalmoscope in glaucoma and glaucoma suspects.

Methods: Thirty patients, including 21 with confirmed glaucoma (9 men; average age 75 ± 8 years) and 9 glaucoma suspects (5 men; average age 64 ± 9 years), were studied. All patients had intraocular pressure measurements, Humphrey visual field assessment, optical coherence tomography, and a 10-second videoscopy of the retinal circulation. The retinal vasculature recordings (46° field of view at 30 frames per second) were analyzed to extract SVP amplitudes.

Results: SVPs were detected and quantified in 100% of patients with glaucoma and those with suspected glaucoma using the novel device. The average SVP amplitudes in glaucoma and glaucoma suspects were 42.6% ± 10.7% and 34% ± 6.7%, respectively.

Conclusions: Our results suggest that a novel tablet-based ophthalmoscope can aid in documenting and objectively quantifying SVPs in all patients.

Translational Relevance: Outcomes of this study provide an innovative, portable, noninvasive, and inexpensive solution for objective assessment of SVPs, which may have clinical relevance in glaucoma screening.
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http://dx.doi.org/10.1167/tvst.9.4.19DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7396170PMC
March 2020

Management of open-angle glaucoma by primary eye-care practitioners: toward a personalised medicine approach.

Clin Exp Optom 2021 Apr 29;104(3):367-384. Epub 2021 Mar 29.

Ophthalmology Department, Prince of Wales Hospital, Sydney, Australia.

Glaucoma is the leading cause of irreversible blindness worldwide. As a chronic disease, glaucoma presents a significant burden to the individual, health-care provider and the health-care system. Currently, strategies for treating glaucoma are focused on lowering intraocular pressure, which is aimed at slowing or arresting disease progression over time. This is the only current accepted therapeutic strategy for glaucoma, and can be achieved using topical drugs, laser trabeculoplasty, filtration surgery or cyclodestructive techniques. The lowering of intraocular pressure has been well-supported by numerous large-scale seminal clinical trials in primary open-angle glaucoma, in both its early and advanced stages. Although such guidance remains current, in the last 10-years, there has been a significant evolution in preferred first-line therapies in the treatment of open-angle glaucoma with a resultant shift in practice patterns, particularly early in the course of the disease. These changes reflect both from the perspective of the doctor - in titrating the most effective and least risky treatment modality - and the perspective of the patient, in consenting to a treatment that preserves vision and results in minimal negative impact on quality of life. In this review, the most recent evidence regarding treatment modalities for early primary open-angle glaucoma is presented and an updated framework for management guidance is proposed.
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http://dx.doi.org/10.1111/cxo.13114DOI Listing
April 2021

Cardiovascular Disease Predicts Structural and Functional Progression in Early Glaucoma.

Ophthalmology 2021 01 28;128(1):58-69. Epub 2020 Jul 28.

Department of Ophthalmology, Flinders University, Adelaide, Australia.

Purpose: To investigate the association between cardiovascular disease and baseline structural defects and disease progression in glaucoma.

Design: Prospective, longitudinal study of preperimetric and perimetric glaucoma.

Participants: Two thousand six hundred twenty-eight eyes from 1314 participants recruited to the Progression Risk of Glaucoma: Relevant SNPs with Significant Association (PROGRESSA) study were evaluated for baseline and longitudinal structural thinning using spectral-domain OCT and for visual field progression on Humphrey visual field (HVF) assessment.

Methods: Patients were classified as either predominantly macula ganglion cell-inner plexiform layer (mGCIPL), predominantly peripapillary retinal nerve fiber layer (pRNFL), or both mGCIPL and pRNFL structural change at enrollment, and then evaluated for longitudinal OCT or HVF progression. Cardiovascular disease and medication characteristics of the participants were compared with a reference group of stable patients.

Main Outcome Measures: OCT and HVF baseline status and longitudinal progression.

Results: After accounting for age and cardiovascular characteristics, patients with predominantly mGCIPL thinning at baseline showed a higher prevalence of hypertension (odds ratio [OR], 2.70; 95% confidence interval [CI], 1.66-4.41; P < 0.001), antihypertensive use (OR, 2.03; 95% CI, 1.20-3.46; P = 0.008), and statin use (OR, 1.98; 95% CI, 1.07-3.66; P = 0.029) than reference patients. Patients with predominantly pRNFL thinning exhibited a comparable prevalence of cardiovascular disease or medication with reference patients. Review of longitudinal OCT and HVF data (mean follow-up, 5.34 ± 1.29 years) showed that hypertension was associated with an increased risk of both OCT (OR, 1.79; 95% CI, 1.17-2.75; P = 0.006) and HVF progression (OR, 1.92; 95% CI, 1.18-3.15; P = 0.013). A 1-standard deviation (approximately 21 mmHg) increase in systolic blood pressure at baseline was associated with a greater risk of OCT progression (OR, 1.27; 95% CI, 1.01-1.63; P = 0.041) and HVF progression (OR, 1.32; 95% CI, 1.01-1.73; P = 0.043). The association between systolic blood pressure and structural progression was comparable to that observed between intraocular pressure and structural progression (OR, 1.30; 95% CI, 1.01-1.67; P = 0.039).

Conclusions: Cardiovascular disease is an important risk factor for glaucoma progression.
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http://dx.doi.org/10.1016/j.ophtha.2020.06.067DOI Listing
January 2021

Assessment of Saccadic Velocity at the Bedside.

Neuroophthalmology 2020 Apr 28;44(2):71-75. Epub 2019 May 28.

Faculty of Medicine, University of New South Wales, Sydney, Australia.

Saccades are a key component for the assessment and diagnosis of Neuro-ophthalmological disorders. Traditionally, clinicians have been taught to use large amplitude saccades (LAS) to assess saccadic velocity (SV), when small amplitude saccades (SAS) may be more effective. This study aimed to evaluate the advantages of SAS over LAS by presenting a video to 108 clinicians where both methods were used to assess a patient with a unilateral partial 6th nerve palsy. SAS was the preferred method in identifying the 6th nerve palsy by 43/55 (78.2%) of Neurologists, and 36/53 (67.9%) of Ophthalmologists. These findings indicate that SAS may be a more effective method than LAS for determining SV.
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http://dx.doi.org/10.1080/01658107.2019.1616776DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7202411PMC
April 2020

An Intraocular Pressure Polygenic Risk Score Stratifies Multiple Primary Open-Angle Glaucoma Parameters Including Treatment Intensity.

Ophthalmology 2020 07 7;127(7):901-907. Epub 2020 Jan 7.

Department of Ophthalmology, Flinders University, Flinders Medical Centre, Bedford Park, Australia.

Purpose: To examine the combined effects of common genetic variants associated with intraocular pressure (IOP) on primary open-angle glaucoma (POAG) phenotype using a polygenic risk score (PRS) stratification.

Design: Cross-sectional study.

Participants: For the primary analysis, we examined the glaucoma phenotype of 2154 POAG patients enrolled in the Australian and New Zealand Registry of Advanced Glaucoma, including patients recruited from the United Kingdom. For replication, we examined an independent cohort of 624 early POAG patients.

Methods: Using IOP genome-wide association study summary statistics, we developed a PRS derived solely from IOP-associated variants and stratified POAG patients into 3 risk tiers. The lowest and highest quintiles of the score were set as the low- and high-risk groups, respectively, and the other quintiles were set as the intermediate risk group.

Main Outcome Measures: Clinical glaucoma phenotype including maximum recorded IOP, age at diagnosis, number of family members affected by glaucoma, cup-to-disc ratio, visual field mean deviation, and treatment intensity.

Results: A dose-response relationship was found between the IOP PRS and the maximum recorded IOP, with the high genetic risk group having a higher maximum IOP by 1.7 mmHg (standard deviation [SD], 0.62 mmHg) than the low genetic risk group (P = 0.006). Compared with the low genetic risk group, the high genetic risk group had a younger age of diagnosis by 3.7 years (SD, 1.0 years; P < 0.001), more family members affected by 0.46 members (SD, 0.11 members; P < 0.001), and higher rates of incisional surgery (odds ratio, 1.5; 95% confidence interval, 1.1-2.0; P = 0.007). No statistically significant difference was found in mean deviation. We further replicated the maximum IOP, number of family members affected by glaucoma, and treatment intensity (number of medications) results in the early POAG cohort (P ≤ 0.01).

Conclusions: The IOP PRS was correlated positively with maximum IOP, disease severity, need for surgery, and number of affected family members. Genes acting via IOP-mediated pathways, when considered in aggregate, have clinically important and reproducible implications for glaucoma patients and their close family members.
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http://dx.doi.org/10.1016/j.ophtha.2019.12.025DOI Listing
July 2020

Effect of phacoemulsification cataract surgery on intraocular pressure in early glaucoma: A prospective multi-site study.

Clin Exp Ophthalmol 2020 05 13;48(4):442-449. Epub 2020 Feb 13.

Department of Ophthalmology, Flinders University, Flinders Medical Centre, Adelaide, South Australia, Australia.

Importance: Cataract and primary open-angle glaucoma (POAG) commonly co-exist, and cataract surgery is thought to reduce intraocular pressure (IOP), the major modifiable risk factor of POAG.

Background: Previous studies exploring the effect of cataract surgery on IOP are limited by retrospective design, lack of a control group, medication use and washout and loss to follow up.

Design: Prospective, multicentre, matched case-control Australian study.

Participants: 171 eyes of 108 POAG patients who underwent cataract surgery, matched to 171 control eyes.

Methods: Serial longitudinal IOP measurements were compared before and after cataract surgery, and relative to the controls. A mixed-effect model was used for the longitudinal data.

Main Outcome Measures: Change in IOP.

Results: The mean follow-up time was 4.8 (1.4) years. Cataract surgery reduced mean IOP by 2.22 mmHg (95% confidence interval: 1.93-2.52 mmHg, P < .001) with 59 eyes (34%) achieving at least 3 mmHg reduction. Compared to matched controls, the mean reduction in IOP was 1.75 mmHg (95% confidence interval 1.15-2.33 mmHg; P < .001). Higher preoperative IOP and being on fewer topical glaucoma medications preoperatively were strongly predictive of a larger IOP reduction in a multivariable model. Anterior chamber depth was not associated with IOP reduction. Eyes with preoperative IOP ≥24 mmHg had a mean IOP reduction of 4.03 mmHg with 81% experiencing at least 3 mmHg reduction. Sub-analysis of medication naïve and pseudoexfoliation patients showed similar results.

Conclusions And Relevance: Cataract surgery has a confirmed effect in reducing IOP in a "real world" setting of early glaucoma patients.
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http://dx.doi.org/10.1111/ceo.13724DOI Listing
May 2020

Multitrait analysis of glaucoma identifies new risk loci and enables polygenic prediction of disease susceptibility and progression.

Nat Genet 2020 02 20;52(2):160-166. Epub 2020 Jan 20.

Eye Department, Greenlane Clinical Centre, Auckland District Health Board, Auckland, New Zealand.

Glaucoma, a disease characterized by progressive optic nerve degeneration, can be prevented through timely diagnosis and treatment. We characterize optic nerve photographs of 67,040 UK Biobank participants and use a multitrait genetic model to identify risk loci for glaucoma. A glaucoma polygenic risk score (PRS) enables effective risk stratification in unselected glaucoma cases and modifies penetrance of the MYOC variant encoding p.Gln368Ter, the most common glaucoma-associated myocilin variant. In the unselected glaucoma population, individuals in the top PRS decile reach an absolute risk for glaucoma 10 years earlier than the bottom decile and are at 15-fold increased risk of developing advanced glaucoma (top 10% versus remaining 90%, odds ratio = 4.20). The PRS predicts glaucoma progression in prospectively monitored, early manifest glaucoma cases (P = 0.004) and surgical intervention in advanced disease (P = 3.6 × 10). This glaucoma PRS will facilitate the development of a personalized approach for earlier treatment of high-risk individuals, with less intensive monitoring and treatment being possible for lower-risk groups.
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http://dx.doi.org/10.1038/s41588-019-0556-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8056672PMC
February 2020

Impact of referral refinement on management of glaucoma suspects in Australia.

Clin Exp Optom 2020 09 18;103(5):675-683. Epub 2019 Dec 18.

Centre for Eye Health, The University of New South Wales, Sydney, Australia.

Background: In ageing populations, the prevalence of chronic diseases such as glaucoma is projected to increase, placing additional demands on limited health-care resources. In the UK, the demand for secondary care in hospital eye clinics was inflated by high rates of false positive glaucoma referrals. Collaborative care models incorporating referral refinement, whereby glaucoma suspect referrals are triaged by suitably trained optometrists through further testing, can potentially reduce false positive referrals. This study examined the impact of a referral refinement model on the accuracy of glaucoma referrals in Australia.

Methods: Optometrist-initiated glaucoma suspect referrals to the Glaucoma Management Clinic (Sydney, Australia) were prospectively recruited. Glaucoma suspect referrals arising from two pathways were eligible for inclusion, either directly from a community optometrist (standard care) or following comprehensive assessment at the Centre for Eye Health (referral refinement). Main outcome measures were the positive predictive value and false positive rate of referrals. The impact of referral letter content on management outcomes was also investigated.

Results: Of 464 referrals received between March 2015 and June 2018, 252 were for treatment of naïve glaucoma suspects and eligible for inclusion. Following ophthalmological assessment, 45.6 per cent (n = 115/252) were prescribed treatment for open angle glaucoma or ocular hypertension. Positive predictive value of community optometry referrals was 33.8 per cent (n = 25/74) and 50.6 per cent (n = 90/178) following referral refinement. The first visit discharge (false positive) rate was 26 per cent (n = 19/74) for community referrals compared to four per cent (n = 8/178) with referral refinement. Positive predictive value increased with the number of abnormal clinical examination findings associated with referral (χ test, p < 0.0001). The number of abnormal findings reported in referrals was significantly higher with referral refinement compared to without (n = 1.9 versus 1.5, t-test, p < 0.0001).

Conclusion: Referral refinement can improve the diagnostic accuracy of optometry-initiated referrals for glaucoma suspects in Australia, thereby decreasing unnecessary referrals to hospital and other secondary clinics.
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http://dx.doi.org/10.1111/cxo.13030DOI Listing
September 2020

Intracranial Arterial Compression of the Anterior Visual Pathway.

Neuroophthalmology 2019 Nov 22;43(5):295-304. Epub 2019 Jan 22.

Prince of Wales Hospital Clinical School, The University of New South Wales, Sydney, Australia.

Compression of anterior visual pathway (AVP) structures by intracranial arteries is observed not infrequently on neuroimaging. Whether or not such compression results in damage to these structures, however, remains unclear. This information is important to define as AVP compression by intracranial arteries may be a causative factor in patients with otherwise unexplained visual dysfunction. In a single centre, 37 patients with evidence of intracranial artery AVP compression demonstrated on magnetic resonance imaging were identified by retrospective review of case records over the period 2011-2017. Variables were collected, including patient demographics, visual acuity, visual fields, pupillary reactions and optic disc appearance for patients in the case series. Visual field deficits correlated with compression sites in the 37 patients examined. Internal carotid artery-optic nerve compression was the most frequent (unilateral compression = 9, bilateral compression = 14), followed by chiasmal compression by the anterior cerebral artery ( = 8) and a combination of optic nerve and chiasmal compression ( = 5). Visual acuity and visual fields were stable on follow-up (mean 4 years) in 24 of 26 cases (93%). We conclude that AVP compression by intracranial arteries may be a causative factor in unexplained visual dysfunction. The visual defects are largely non-progressive.
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http://dx.doi.org/10.1080/01658107.2019.1566383DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6844511PMC
November 2019

Clinical Evaluation of Swedish Interactive Thresholding Algorithm-Faster Compared With Swedish Interactive Thresholding Algorithm-Standard in Normal Subjects, Glaucoma Suspects, and Patients With Glaucoma.

Am J Ophthalmol 2019 12 27;208:251-264. Epub 2019 Aug 27.

Centre for Eye Health, University of New South Wales, Kensington, New South Wales; School of Optometry and Vision Science, University of New South Wales, Kensington, New South Wales.

Purpose: To compare the visual fields results obtained using the Swedish interactive thresholding algorithm-Standard (SS) and the Swedish interactive thresholding algorithm-Faster (SFR) in normal subjects, glaucoma suspects, and patients with glaucoma and to quantify potential time-saving benefits of the SFR algorithm.

Design: Prospective, cross-sectional study.

Methods: One randomly selected eye from 364 patients (77 normal subjects, 178 glaucoma suspects, and 109 patients with glaucoma) seen in a single institution underwent testing using both SS and SFR on the Humphrey Field Analyzer. Cumulative test time using each algorithm was compared after accounting for different rates of test reliability. Pointwise and cluster analysis was performed to determine whether there were systematic differences between algorithms.

Results: Using SFR had a greater rate of unreliable results (29.3%) compared with SS (7.7%, P < .0001). This was mainly because of high false positive rates and seeding point errors. However, modeled test times showed that using SFR could obtain a greater number of reliable results within a shorter period of time. SFR resulted in higher sensitivity values (on average 0.5 dB for patients with glaucoma) that was greater under conditions of field loss (<19 dB). Cluster analysis showed no systematic patterns of sensitivity differences between algorithms.

Conclusions: After accounting for different rates of test reliability, SFR can result in significant time savings compared with SS. Clinicians should be cognizant of false positive rates and seeding point errors as common sources of error for SFR. Results between algorithms are not directly interchangeable, especially if there is a visual field deficit <19 dB.
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http://dx.doi.org/10.1016/j.ajo.2019.08.013DOI Listing
December 2019

All that fails to abduct may not be an abducens palsy.

Clin Exp Ophthalmol 2019 11 31;47(8):1105-1106. Epub 2019 Jul 31.

Department of Ophthalmology, The Prince of Wales Hospital, Sydney, New South Wales, Australia.

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http://dx.doi.org/10.1111/ceo.13590DOI Listing
November 2019

Macular Ganglion Cell-Inner Plexiform Layer Loss Precedes Peripapillary Retinal Nerve Fiber Layer Loss in Glaucoma with Lower Intraocular Pressure.

Ophthalmology 2019 08 22;126(8):1119-1130. Epub 2019 Mar 22.

Department of Ophthalmology, Flinders University, Bedford Park, Australia. Electronic address:

Purpose: To investigate which clinical measures influence whether an individual demonstrates earliest glaucomatous structural progression on peripapillary retinal nerve fiber layer (pRNFL) or macular ganglion cell-inner plexiform layer (mGCIPL).

Design: Prospective, longitudinal cohort study.

Participants: Two hundred seventy-one eyes from 207 individuals with statistically significant evidence of glaucomatous progression on OCT Guided Progression Analysis (GPA) software were drawn from a total of 1271 eyes from 686 individuals categorized as glaucoma suspect or having early manifest glaucoma undergoing glaucoma surveillance.

Methods: Individuals demonstrating earliest evidence of longitudinal progression on mGCIPL GPA event analysis were compared with individuals demonstrating evidence of earliest longitudinal progression on pRNFL GPA event analysis.

Main Outcome Measures: Correlation of OCT event change analysis with intraocular pressure (IOP), clinical variables, and baseline thickness of the pRNFL and mGCIPL.

Results: Intraocular pressure, baseline pRNFL thickness, baseline mGCIPL thickness, and systemic hypertension were associated with location of first progression. Eyes demonstrating earliest longitudinal progression on mGCIPL had significantly lower maximum-recorded pretreatment IOP (mean difference, 3.90 mmHg; 95% confidence interval [CI], 2.37-5.43 mmHg; P < 0.001). The interval between progression on pRNFL and progression on mGCIPL increased by 12.4 months for every 5-mmHg increase in IOP (95% CI, 10.32-15.72 months). Eyes demonstrating earliest longitudinal progression on mGCIPL showed significantly lower baseline average pRNFL thickness than eyes progressing on pRNFL first (mean difference, 7.07 μm; 95% CI, 4.38-9.77 μm; P < 0.001). Eyes progressing first on mGCIPL parameters were 3.03 times more likely to demonstrate a new paracentral field defect than eyes progressing first on pRNFL parameters (odds ratio, 3.03; 95% CI, 1.26-7.28; P = 0.01).

Conclusions: Clinical features, particularly pretreatment IOP, influence whether structural glaucoma progression is detected earlier with mGCIPL or pRNFL imaging. These data support the usefulness of mGCIPL imaging in addition to pRNFL analysis for detection of glaucoma progression, particularly in patients with normal IOP.
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http://dx.doi.org/10.1016/j.ophtha.2019.03.016DOI Listing
August 2019

Corneal indentation works, almost universally, and especially when applied as per the corneal indentation protocol.

Surv Ophthalmol 2019 Jul - Aug;64(4):588-589. Epub 2019 Mar 12.

Department of Ophthalmology, Prince of Wales Hospital, Sydney, Australia; University of New South Wales, Sydney, Australia; Chatswood Eye Specialists, Sydney, Australia; Chatswood Private Hospital, Sydney, Australia.

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http://dx.doi.org/10.1016/j.survophthal.2019.03.001DOI Listing
November 2019
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