Faculty Bibliography

BACKGROUND/AIMS:The objective of this study is to evaluate the accuracy and speed of trainees and experienced glaucoma specialists using the MatchedFlicker software against the manual examination of stereoscopic disc photographs for detecting glaucomatous optic disc change. METHODS:Three experienced glaucoma specialists, two resident ophthalmologists and one glaucoma fellow from multiple institutions independently evaluated the same 140 image pairs from 100 glaucomatous/ocular hypertensive eyes using a handheld stereo viewer and the MatchedFlicker programme. Fifty had progression to glaucoma as determined by the Ocular Hypertension Treatment Study (OHTS) Optic Disc Reading Group and endpoint committee, and 50 more were negative controls for progression with photos taken a few minutes apart. Twenty photo pairs from each of the two groups were duplicated for reviewer variability analysis. The initial viewing method was randomised and then alternated for each group of 70 image pairs. Reviewer accuracy and evaluation time for each method were measured. RESULTS:Evaluators averaged 8.6 s faster per image pair (26%) with the MatchedFlicker programme than with the stereo viewer (p=0.0007). Evaluators correctly identified more image pairs when using the MatchedFlicker software over the stereo viewer (p=0.0003). There was no significant difference between the expert and trainee group in speed or overall accuracy for either method. Experts were significantly more consistent than trainees with the duplicate image pairs (p=0.029). Trainees appeared more reluctant to designate eyes as showing glaucoma progression than experts. CONCLUSIONS:Both expert glaucoma specialists and ophthalmologists in various stages of training had greater accuracy and speed with the MatchedFlicker programme than with a handheld stereoscopic viewer.

Purpose/UNASSIGNED:Sex hormones may be associated with primary open-angle glaucoma (POAG), although the mechanisms are unclear. We previously observed that gene variants involved with estrogen metabolism were collectively associated with POAG in women but not men; here we assessed gene variants related to testosterone metabolism collectively and POAG risk. Methods/UNASSIGNED:We used two datasets: one from the United States (3853 cases and 33,480 controls) and another from Australia (1155 cases and 1992 controls). Both datasets contained densely called genotypes imputed to the 1000 Genomes reference panel. We used pathway- and gene-based approaches with Pathway Analysis by Randomization Incorporating Structure (PARIS) software to assess the overall association between a panel of single nucleotide polymorphisms (SNPs) in testosterone metabolism genes and POAG. In sex-stratified analyses, we evaluated POAG overall and POAG subtypes defined by maximum IOP (high-tension [HTG] or normal tension glaucoma [NTG]). Results/UNASSIGNED:In the US dataset, the SNP panel was not associated with POAG (permuted P = 0.77), although there was an association in the Australian sample (permuted P = 0.018). In both datasets, the SNP panel was associated with POAG in men (permuted P ≤ 0.033) and not women (permuted P ≥ 0.42), but in gene-based analyses, there was no consistency on the main genes responsible for these findings. In both datasets, the testosterone pathway association with HTG was significant (permuted P ≤ 0.011), but again, gene-based analyses showed no consistent driver gene associations. Conclusions/UNASSIGNED:Collectively, testosterone metabolism pathway SNPs were consistently associated with the high-tension subtype of POAG in two datasets.

The choroid is vascular tissue located underneath the retina and supplies oxygen to the outer retina; any damage to this tissue can be a precursor to retinal diseases. This paper presents an automated method of choroidal segmentation from Enhanced Depth Imaging Optical Coherence Tomography (EDI-OCT) images. The Dijkstra shortest path algorithm is used to segment the choroid-sclera interface (CSI), the outermost border of the choroid. A novel intensity-normalisation technique that is based on the depth of the choroid is used to equalise the intensity of all non-vessel pixels in the choroid region. The outer boundary of choroidal vessel and CSI are determined approximately and incorporated to the edge weight of the CSI segmentation to choose optimal edge weights. This method is tested on 190 B-scans of 10 subjects against choroid thickness (CTh) results produced manually by two graders. For comparison, results obtained by two state-of-the-art automated methods and our proposed method are compared against the manual grading, and our proposed method performed the best. The mean root-mean-square error (RMSE) for finding the CSI boundary by our method is 7.71±6.29 pixels, which is significantly lower than the RMSE for the two other state-of-the-art methods (36.17±11.97 pixels and 44.19±19.51 pixels). The correlation coefficient for our method is 0.76, and 0.51 and 0.66 for the other two state-of-the-art methods. The interclass correlation coefficients are 0.72, 0.43 and 0.56 respectively. Our method is highly accurate, robust, reliable and consistent. This identification can enable to quantify the biomarkers of the choroidin large scale study for assessing, monitoring disease progression as well as early detection of retinal diseases. Identification of the boundary can help to determine the loss or change of choroid, which can be used as features for the automatic determination of the stages of retinal diseases.

PURPOSE: To compare longitudinal glaucoma progression detection using optical coherence tomography (OCT) and visual field (VF). DESIGN: Validity assessment METHOD: We analyzed subjects with more than 5 follow-up visits (every 6 months) in the multi-center Advanced Imaging for Glaucoma Study. Fourier-domain optical coherence tomography (OCT) was used to map the thickness of the peripapillary retinal nerve fiber layer (NFL) and ganglion cell complex (GCC). OCT-based progression detection was defined as a significant negative trend for either NFL or GCC. VF progression was reached if either the event or trend analysis reached significance. RESULT: The analysis included 417 glaucoma suspect/pre-perimetric glaucoma (GS/PPG) eyes and 377 perimetric glaucoma (PG) eyes. In the GS/PPG group, progression was detect in 38.9% of eyes by OCT, significantly more (P<0.001) than the detection rate of 18.7% by VF. In severity-stratified analysis of PG eyes, OCT had significantly higher detection rate in early PG (49.7% vs. 32.0%, p=0.02), but not significantly different in moderate and advanced PG. The rate of NFL thinning declined dramatically in advanced PG, but GCC thinning rate remained relatively steady and allowed good progression detection even in advanced disease. The rate of false positive progression detection in permutated series was over 10% for VF trend analysis in both GS/PPG and PG group, while under 7% for both GCC and NFL. CONCLUSION: OCT is a more sensitive than VF for the detection of progression in early glaucoma. While the value of NFL declines in advanced glaucoma, GCC appears to be a useful progression detector from early to advanced stages.

Telemedicine services facilitate the evaluation, diagnosis, and management of the remote patient. Telemedicine has rapidly flourished in the United States and has improved access to care, outcomes, and patient satisfaction. However, the use of telemedicine in ophthalmology is currently in its infancy and has yet to gain wide acceptance. Current models of telemedicine in ophthalmology are largely performed via "store and forward" methods, but remote monitoring and interactive modalities exist. Although studies have examined the effects of telemedicine, few reports have characterized its current status. We perform a descriptive analysis of the current state of teleophthalmology in the United States. We describe the use of teleophthalmology in the hospital and outpatient settings. We also review the applications to retinopathy of prematurity, diabetic retinopathy, age-related macular degeneration, and glaucoma, as well as anticipated barriers and hurdles for the future adoption of teleophthalmology. With ongoing advances in teleophthalmology, these models may provide earlier detection and more reliable monitoring of vision-threatening diseases.

Ocular imaging has been heavily incorporated into glaucoma management and provides important information that aids in the detection of disease progression. Longitudinal studies have shown that the circumpapillary retinal nerve fiber layer is an important parameter for glaucoma progression detection, whereas other studies have demonstrated that macular parameters, such as the ganglion cell inner plexiform layer and optic nerve head parameters, also are useful for progression detection. The introduction of novel technologies with faster scan speeds, wider scanning fields, higher resolution, and improved tissue penetration has enabled the precise quantification of additional key ocular structures, such as the individual retinal layers, optic nerve head, choroid, and lamina cribrosa. Furthermore, extracting functional information from scans such as blood flow rate and oxygen consumption provides new perspectives on the disease and its progression. These novel methods promise improved detection of glaucoma progression and better insight into the mechanisms of progression that will lead to better targeted treatment options to prevent visual damage and blindness.

PURPOSE/OBJECTIVE:To measure the waste generation and lifecycle environmental emissions from cataract surgery via phacoemulsification in a recognized resource-efficient setting. SETTING/METHODS:Two tertiary care centers of the Aravind Eye Care System in southern India. DESIGN/METHODS:Observational case series. METHODS:Manual waste audits, purchasing data, and interviews with Aravind staff were used in a hybrid environmental lifecycle assessment framework to quantify the environmental emissions associated with cataract surgery. Kilograms of solid waste generated and midpoint emissions in a variety of impact categories (eg, kilograms of carbon dioxide equivalents). RESULTS:Aravind generates 250 grams of waste per phacoemulsification and nearly 6 kilograms of carbon dioxide-equivalents in greenhouse gases. This is approximately 5% of the United Kingdom's phaco carbon footprint with comparable outcomes. A majority of Aravind's lifecycle environmental emissions occur in the sterilization process of reusable instruments because their surgical system uses largely reusable instruments and materials. Electricity use in the operating room and the Central Sterile Services Department (CSSD) accounts for 10% to 25% of most environmental emissions. CONCLUSIONS:Surgical systems in most developed countries and, in particular their use of materials, are unsustainable. Results show that ophthalmologists and other medical specialists can reduce material use and emissions in medical procedures using the system described here.

Primary open-angle glaucoma (POAG) is the most common chronic optic neuropathy worldwide. Epidemiological studies show a robust positive relation between intraocular pressure (IOP) and POAG and modest positive association between IOP and blood pressure (BP), while the relation between BP and POAG is controversial. The International Glaucoma Genetics Consortium (n=27 558), the International Consortium on Blood Pressure (n=69 395), and the National Eye Institute Glaucoma Human Genetics Collaboration Heritable Overall Operational Database (n=37 333), represent genome-wide data sets for IOP, BP traits and POAG, respectively. We formed genome-wide significant variant panels for IOP and diastolic BP and found a strong relation with POAG (odds ratio and 95% confidence interval: 1.18 (1.14-1.21), P=1.8 x 10-27) for the former trait but no association for the latter (P=0.93). Next, we used linkage disequilibrium (LD) score regression, to provide genome-wide estimates of correlation between traits without the need for additional phenotyping. We also compared our genome-wide estimate of heritability between IOP and BP to an estimate based solely on direct measures of these traits in the Erasmus Rucphen Family (ERF; n=2519) study using Sequential Oligogenic Linkage Analysis Routines (SOLAR). LD score regression revealed high genetic correlation between IOP and POAG (48.5%, P=2.1 x 10-5); however, genetic correlation between IOP and diastolic BP (P=0.86) and between diastolic BP and POAG (P=0.42) were negligible. Using SOLAR in the ERF study, we confirmed the minimal heritability between IOP and diastolic BP (P=0.63). Overall, IOP shares genetic basis with POAG, whereas BP has limited shared genetic correlation with IOP or POAG.European Journal of Human Genetics advance online publication, 30 August 2017; doi:10.1038/ejhg.2017.136.

Background: Retinal imaging by optical coherence tomography (OCT) has gained increasing attention in multiple sclerosis and other neuroinflammatory and neurodegenerative disorders. Ambiguous and incomplete reporting of methodology and OCT-derived data have limited the ability to compare data and to apply and generalize findings in the past. To improve this situation, the Advised Protocol for Optical coherence tomography Study Terminology and Elements (APOSTEL) recommendations have been developed to outline core information to be provided when reporting quantitative OCT studies with help of a 9-point checklist (Cruz-Herranz and Balk et al., Neurology 2016). The APOSTEL recommendations currently have the evidence level of an expert opinion (Class IV). Objective: To advance the APOSTEL recommendations for OCT reporting in a formalized procedure towards evidence-based guidelines. Methods: Studies reporting quantitative OCT results published within the last 24 months have been identified by a Pubmed search. The corresponding authors of these 1472 articles will be contacted and asked to participate in an online survey to evaluate and give feedback on the initial APOSTEL recommendations. The feedback obtained will be anonymized and distributed to a panel of international experts for evaluation and revision of the recommendations. After the initial round the corresponding authors who gave feedback will be informed about the intermediate results and asked to participate in the survey for a second time. This procedure will be repeated if necessary following the consensus-building procedure of a DELPHI process. To this end, for each round the feedback obtained as well as any revisions made to the APOSTEL recommendations will be summarized and questionnaires will be used for evaluation in order to reach consensus and to develop evidencebased guidelines for prospective OCT studies. Results: The degree of consensus of the survey's participants will be reported for the initial and the revised versions of the recommendations as well as the revisions made to the initial version. Conclusion: Formal guidelines for the reporting of quantitative OCT studies will be presented as well as the process of how they were developed