Retinal Nerve Fiber Layer Optical Texture Analysis and 10-2 Visual Field Assessment in Glaucoma.

PURPOSE: To apply retinal nerve fiber layer (RNFL) optical texture analysis (ROTA) to 1) investigate the association between papillomacular and papillofoveal bundle defects with 10-2 visual field (VF) sensitivity abnormalities, and 2) integrate the information from RNFL bundle defect and 24-2 VF central test locations to determine the likelihood of 10-2 VF sensitivity abnormalities. DESIGN: Cross-sectional. METHODS: A total of 841 eyes (144 healthy, 317 glaucoma suspect, and 380 glaucoma) of 442 participants were included. Eyes underwent 24-2, and 10-2 VF testing and OCT for ROTA. The borders of RNFL defects were delineated from ROTA, and the involvement of the arcuate, papillomacular, and papillofoveal bundles was determined for each eye. Multilevel logistic regression analysis was applied to evaluate the structure-function association. RESULTS: Papillomacular (92.1%) and papillofoveal (37.9%) RNFL bundle defects were prevalent in eyes with glaucoma. A 10-2 VF location that was projected onto a papillomacular or a papillofoveal RNFL bundle defect had a significantly increased likelihood of reduced sensitivity (ORs of 18.61 at PDP < 5%, and 20.17 at TDP < 5%, respectively, P < .001 for both). When predicting the likelihood of VF abnormality in a 10-2 test location, noticeably higher odds ratios were observed when overlapping with an RNFL bundle defect, compared to when an abnormal corresponding 24-2 central point was present. CONCLUSIONS: Papillomacular and papillofoveal RNFL bundle defects are present in a considerable proportion of eyes with glaucoma. When detected, they significantly increase the likelihood of abnormality in the corresponding central VF test locations assessed by the 10-2 test.

Imaging Assessment of Peripapillary Vessel Diameters in Postmortem Eyes.

PURPOSE: Proof of concept of ex vivo retinal vessel diameter measurements in human postmortem eyes. METHODS: En face near-infrared (IR) images and optical coherence tomography (OCT) of the optic nerve head (ONH) were captured ex vivo with a Heidelberg Engineering Spectralis (Spectralis, version 7.0.4, Image Capture Module, version 1.2.4, Heidelberg Heidelberg, Germany) device, using a custom-made eye chamber holding and positioning the eyes during the image process. Thirty-two formaldehyde-fixated eyes of 16 patients were imaged. In the IR images, two independent graders measured retinal vessel diameters at the intersection of a drawn circle centered on the ONH with diameters of 2.0 mm and 3.4 mm, respectively. The anatomically corresponding measurements between both graders were statistically analyzed using a Wilcoxon signed-rank test. RESULTS: A total of 246 matched measurements of both graders were analyzed across all 32 imaged eyes. Statistically significant differences between the graders were found for arterioles at 2 mm from the ONH. The other measurements did not show statistically significant intergrader differences. The mean values for arteriole diameters were 72.2 µm at 2.0 mm and 61.5 µm at 3.4 mm for grader 1, and 66.4 µm at 2.0 mm and 63.2 µm at 3.4 mm for grader 2. The mean diameter for venules were 75.5 µm at 2.0 mm and 79.3 µm at 3.4 mm for grader 1, and 67.4 µm at 2 mm and 79.1 µm at 3.4 mm for grader 2. CONCLUSION: To the best of our knowledge, this is the first study to present IR image-based retinal vessel diameters in ex vivo postmortem eyes. Retinal IR/OCT imaging is possible, and measurements are reproducible in formaldehyde-fixated human eyes. Fixation artefacts result in lower image quality, and this can impose challenges in correctly detecting, classifying, and measuring retinal vessels.

Optical Coherence Tomography Versus Optic Disc Photo Assessment in Glaucoma Screening.

PRCIS: Optical coherence tomography (OCT) and optic disc photography present valuable but distinct capabilities for glaucoma screening. OBJECTIVE: This review article examines the strengths and limitations of OCT and optic disc photography in glaucoma screening. METHODS: A comprehensive literature review was conducted, focusing on the accuracy, feasibility, cost-effectiveness, and technological advancements in OCT and optic disc photography for glaucoma screening. RESULTS: OCT is highly accurate and reproducible but faces limitations due to its cost and less portable nature, making widespread screening challenging. In contrast, optic disc photos are more accessible and cost-effective but are hindered by subjective interpretation and inconsistent grading reliability. A critical challenge in glaucoma screening is achieving a high PPV, particularly given the low prevalence of the disease, which can lead to a significant number of false positives. The advent of artificial intelligence (AI) and deep learning models shows potential in improving the diagnostic accuracy of optic disc photos by automating the detection of glaucomatous optic neuropathy and reducing subjectivity. However, the effectiveness of these AI models hinges on the quality of training data. Using subjective gradings as training data, will carry the limitations of human assessment into the AI system, leading to potential inaccuracies. Conversely, training AI models using objective data from OCT, such as retinal nerve fiber layer thickness, may offer a promising direction. CONCLUSION: Both OCT and optic disc photography present valuable but distinct capabilities for glaucoma screening. An approach integrating AI technology might be key in optimizing these methods for effective, large-scale screening programs.

Short-term Detection of Fast Progressors in Glaucoma: The Fast Progression Assessment through Clustered Evaluation (Fast-PACE) Study.

PURPOSE: To evaluate the performance of an intensive, clustered testing approach in identifying eyes with rapid glaucoma progression over 6 months in the Fast Progression Assessment through Clustered Evaluation (Fast-PACE) Study. DESIGN: Prospective cohort study. PARTICIPANTS: A total of 125 eyes from 65 primary open-angle glaucoma (POAG) subjects. METHODS: Subjects underwent 2 sets of 5 weekly visits (clusters) separated by an average of 6 months and then were followed with single visits every 6 months for an overall mean follow-up of 25 months (mean of 17 tests). Each visit consisted of testing with standard automated perimetry (SAP) 24-2 and 10-2, and spectral-domain OCT (SD-OCT). Progression was assessed using trend analyses of SAP mean deviation (MD) and retinal nerve fiber layer (RNFL) thickness. Generalized estimating equations were applied to adjust for correlations between eyes for confidence interval (CI) estimation and hypothesis testing. MAIN OUTCOME MEASURES: Diagnostic accuracy of the 6-month clustering period to identify progression detected during the overall follow-up. RESULTS: A total of 19 of 125 eyes (15%, CI, 9%-24%) progressed based on SAP 24-2 MD over the 6-month clustering period. A total of 14 eyes (11%, CI, 6%-20%) progressed on SAP 10-2 MD, and 16 eyes (13%, CI, 8%-21%) progressed by RNFL thickness, with 30 of 125 eyes (24%, CI, 16%-34%) progressing by function, structure, or both. Of the 35 eyes progressing during the overall follow-up, 25 had progressed during the 6-month clustering period, for a sensitivity of 71% (CI, 53%-85%). Of the 90 eyes that did not progress during the overall follow-up, 85 also did not progress during the 6-month period, for a specificity of 94% (CI, 88%-98%). Of the 14 eyes considered fast progressors by SAP 24-2, SAP 10-2, or SD-OCT during the overall follow-up, 13 were identified as progressing during the 6-month cluster period, for a sensitivity of 93% (CI, 66%-100%) for identifying fast progression with a specificity of 85% (CI, 77%-90%). CONCLUSIONS: Clustered testing in the Fast-PACE Study detected fast-progressing glaucoma eyes over 6 months. The methodology could be applied in clinical trials investigating interventions to slow glaucoma progression and may be of value for short-term assessment of high-risk subjects. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references in the Footnotes and Disclosures at the end of this article.

Assessment of macular and peripapillary choroidal thickness in non-arteritic anterior ischemic optic neuropathy: A meta-analysis.

BACKGROUND: Non-arteritic anterior ischemic optic neuropathy (NAION) is the most common optic neuropathy in adults aged ≥ 50 years. Transient non-perfusion or hypoperfusion of the optic nerve head circulation is believed to be the underlying cause of NAION. It has been suggested that peripapillary choroidal thickness (PCT) is altered after ischemic disorders of the optic nerve head, but the results have not always been consistent. To address this issue and provide evidence for the pathogenesis of NAION, we performed a meta-analysis to systematically evaluate macular choroidal thickness (MCT) and PCT in patients with NAION. METHODS: A comprehensive literature search of PubMed, Embase, Cochrane Library, and Web of Science databases was performed until August 31, 2022. The main inclusion criterion was a case-control study in which MCT and PCT were measured using optical coherence tomography in patients with NAION. Mean difference (MD) and 95% confidence interval were calculated for continuous estimates. The Review Manager (V5.40) was used for the analysis. RESULTS: Nine studies comprising 663 eyes (283 NAION eyes and 380 healthy control eyes) were included (Newcastle-Ottawa Scale score ≥ 5). MCT and PCT were higher in eyes with chronic NAION (MD = 19.16, P = .04; MD = 35.36, P < .00001) and NAION fellow eyes (MD = 30.35, P = .0006; MD = 29.86, P = .04) than in healthy controls. No difference was noted in the MCT between eyes with acute NAION and healthy controls (MD = 2.99, P = .87). CONCLUSION: Increased MCT and PCT may be important anatomical and physiological features of the eyes in patients with NAION.

SD-OCT assessment and visual field changes 1 year or more after a single episode of unilateral acute primary angle closure / Avaliação do SD-OCT e mudanças do campo visual 1 ano ou mais após episódio único de fechamento angular primário agudo unilateral

ABSTRACT Objective: To evaluate structural and visual field (VF) changes after ≥1 year of a single acute primary angle closure (APAC) attack using spectral-domain optical coherence tomography (SD-OCT) and standard automated perimetry (SAP). Methods: Patients with a single unilateral APAC crisis at least 1 year ago were included consecutively from 2013 to 2016. Contralateral eye was used as control. All patients underwent ophthalmic examination, RNFL imaging by SD-OCT, and SAP using Octopus 1-2-3. Results: 54 eyes (27 patients) were enrolled. Male-to-female ratio was 1:2. Mean time for the SD-OCT and SAP assessment after the crisis was 5.0±5.1 (1.0-23.5) years, and IOP was 52.5±9.8 mmHg. In APAC eyes, the thicknesses of all quadrants of peripapillary RNFL (36.3%; P<0.001) and some macular sections (from 2.1% to 4.7%; P<0.01) were reduced compared to contralateral eyes. Additionally, in APAC eyes, the mean defect on VF was negatively and statistically correlated with the reduction of all quadrants of peripapillary RNFL thickness. Conclusion: A single episode of APAC was associated with peripapillary RNFL and macular thickness and with VF defects after ≥1 year of the crisis in the affected eye. Statistically meaningful correlations were found between structural and functional damage.

RESUMO Objetivo: Avaliar alterações estruturais e do campo visual 1 ano ou mais após uma crise única de fechamento angular primário agudo utilizando tomografia de coerência óptica de domínio espectral e perimetria automatizada padronizada. Métodos: Pacientes que apresentaram crise unilateral única de fechamento angular primário agudo há pelo menos 1 ano foram consecutivamente incluídos entre 2013 e 2016. Os olhos contralaterais foram utilizados como controles. Todos os pacientes foram submetidos a exame oftalmológico, avaliação das camadas de fibras nervosas da retina utilizando tomografia de coerência óptica de domínio espectral e perimetria automatizada padronizada com o Octopus 1-2-3. Resultados: Foram incluídos 54 olhos (27 pacientes) com razão homem:mulher de 1:2. O tempo médio após a crise foi de 5,0±5,1 anos (1,0 a 23,5) e a pressão intraocular na crise foi 52,5±9,8mmHg. Nos olhos com fechamento angular primário agudo, todas as espessuras das camadas de fibras nervosas da retina peripapilares (36,3%; p<0,001) e de algumas seções maculares (de 2,1 a 4,7%; p<0,01) estavam reduzidas em comparação aos olhos contralaterais. Além do mais, nos olhos submetidos a fechamento angular primário agudo, o mean defect do campo visual foi estatisticamente e negativamente correlacionado com a redução da espessura de todos os quadrantes peripapilares da camada de fibras nervosas da retina. Conclusão: Um único episódio de fechamento angular primário agudo foi associado com redução na espessura da camada de fibras nervosas da retina peripapilar e da espessura macular e com defeitos de campo visual 1 ano ou mais após a crise no olho afetado. Correlações estatisticamente significativas foram identificadas entre danos estruturais e funcionais.

Assessment of patient specific information in the wild on fundus photography and optical coherence tomography.

In this paper we analyse the performance of machine learning methods in predicting patient information such as age or sex solely from retinal imaging modalities in a heterogeneous clinical population. Our dataset consists of N = 135,667 fundus images and N = 85,536 volumetric OCT scans. Deep learning models were trained to predict the patient's age and sex from fundus images, OCT cross sections and OCT volumes. For sex prediction, a ROC AUC of 0.80 was achieved for fundus images, 0.84 for OCT cross sections and 0.90 for OCT volumes. Age prediction mean absolute errors of 6.328 years for fundus, 5.625 years for OCT cross sections and 4.541 for OCT volumes were observed. We assess the performance of OCT scans containing different biomarkers and note a peak performance of AUC = 0.88 for OCT cross sections and 0.95 for volumes when there is no pathology on scans. Performance drops in case of drusen, fibrovascular pigment epitheliuum detachment and geographic atrophy present. We conclude that deep learning based methods are capable of classifying the patient's sex and age from color fundus photography and OCT for a broad spectrum of patients irrespective of underlying disease or image quality. Non-random sex prediction using fundus images seems only possible if the eye fovea and optic disc are visible.

Diagnostic validity of optic nerve head colorimetric assessment and optical coherence tomography angiography in patients with glaucoma.

BACKGROUND/AIMS: The aim of this study was to assess the optic nerve head (ONH) and macular vessel density with optical coherence tomography angiography (OCT-A) and the ONH haemoglobin (ONH Hb) amount with Laguna ONhE program in open-angle glaucoma (OAG) patients. METHODS: In this prospective observational cross-sectional study, 67 OAG patients and 41 healthy age-sex frequency matched subjects were examined with OCT-A and retinal photos. The circumpapillary (wcpVD), optic nerve head (iVD) and macular (wmVD) capillary vessel density of OCT-A and ONH colorimetric assessment to determine the ONH Hb amount using the Laguna ONhE program were evaluated. RESULTS: Significant differences between normal subjects and glaucoma patients in the wcpVD (22.18±3.42 vs 16.03±2.89%; p<0.001), iVD (18.31±5.56 vs 12.52±4.67%; p<0.001), wmVD (15.60±2.34 vs 13.34±2.32%; p<0.001) and amount of ONH Hb (71.10±1.67 vs 68.86±2.46%; p<0.001) and in the papillary cup (68.14±5.25 vs 64.77±5.08%; p=0.001) were found. The Laguna ONhE glaucoma discriminant function (GDF) index had a negative value in the OAG patients and normal values in healthy subjects (-18.76±13.31 vs 7.98±14.09; p<0.001). The area under the receiver operating characteristic (ROC) curve (AUROC) for discriminating between healthy and glaucomatous eyes was highest for wcpVD (0.93; 95% CI 0.86 to 0.97, p<0.0001), followed by GDF (0.92; 95% CI 0.86 to 0.97, p<0.0001), iVD (0.79; 95% CI 0.70 to 0.86; p<0.0001) and ONH Hb (0.78; 95% CI 0.69 to 0.85, p<0.0001). Pair wise comparisons showed that the AUROC of wcpVD (0.93) was not significantly different than GDF (0.92) (p=0.855). CONCLUSION: Laguna ONhE program and OCT-A have similar diagnostic validity in open-angle glaucoma patients.

Longitudinal assessment of optic nerve head changes using optical coherence tomography in a primate microbead model of ocular hypertension.

In humans, the longitudinal characterisation of early optic nerve head (ONH) damage in ocular hypertension (OHT) is difficult as patients with glaucoma usually have structural ONH damage at the time of diagnosis. Previous studies assessed glaucomatous ONH cupping by measuring the anterior lamina cribrosa depth (LCD) and minimal rim width (MRW) using optical coherence tomography (OCT). In this study, we induced OHT by repeated intracameral microbead injections in 16 cynomolgus primates (10 unilateral; 6 bilateral) and assessed the structural changes of the ONH longitudinally to observe early changes. Elevated intraocular pressure (IOP) in OHT eyes was maintained for 7 months and serial OCT measurements were performed during this period. The mean IOP was significantly elevated in OHT eyes when compared to baseline and compared to the control eyes. Thinner MRW and deeper LCD values from baseline were observed in OHT eyes with the greatest changes seen between month 1 and month 2 of OHT. Both the mean and maximum IOP values were significant predictors of MRW and LCD changes, although the maximum IOP was a slightly better predictor. We believe that this model could be useful to study IOP-induced early ONH structural damage which is important for understanding glaucoma pathogenesis.

Assessment of changes in the macula and optic nerve head using optical coherence tomography in patients with attention deficit hyperactivity disorder. / Evaluación de los cambios en la mácula y en el nervio óptico mediante tomografía de coherencia óptica en pacientes con trastorno por déficit de atención e hiperactividad.

INTRODUCTION: To assess if there are any differences in macular and papillary thickness using optical coherence tomography (OCT) in patients with attention deficit hyperactivity disorder (ADHD) compared with a control group, including if there are differences between ADHD patients with and without treatment. METHODS: Prospective observational study including 92 eyes of 46 patients divided into 2 groups: 46 eyes of 23 patients with ADHD, and a control group of 46 eyes of 23 healthy patients. The group of patients with ADHD was subdivided into those on treatment with methylphenidate (n=28) and those not on treatment (n=18). The macular thickness, the ganglion cell complex (GCC), and the retinal nerve fibre layer (RNFL) at the papillary level were measured in 12 sectors. RESULTS: A lower central macular thickness was observed in the ADHD patients than in the controls (257.4±20µm versus 267.5±20µm, P=.013), with no differences observed in the GCC (P=.566), or in the RNFL (P=.095). There were no differences in the patients with ADHD with and without treatment, as regards macular thickness and the GCC (P=.160 and P=.375 respectively), but a lower foveal thickness (P=.018) and RNFL in 5/12 sectors at the papillary level (P=.033) were observed in those without treatment. CONCLUSIONS: A lower macular thickness was observed in patients with ADHD than in controls. In addition, patients with ADHD without treatment had a lower thickness of the fovea and RNFL than those patients on treatment.

Why Miss the Chance? Incidental Findings while Telescreening for Diabetic Retinopathy.

PURPOSE: To report on incidental pathological findings met while screening for Diabetic Retinopathy (DR) in Diabetes Clinics (DC) by ophthalmologist-graded digital fundus imaging. METHODS: At the DC of Pescara (central Italy), for 3,859 eyes of 1,930 consecutive patients having not undergone fundus examination in the last year, two mydriatic fundus digital images, taken with a CenterVue DRS Digital Retinal Camera, were sent along with Best Corrected Visual Acuity, on a "store-and-forward" basis, to an ophthalmologist trained in DR screening, and graded according to the UK Diabetic Eye Screening Programme. Incidental fundus abnormalities other than DR were reported. RESULTS: No adverse event to mydriasis was reported. One hundred and eighty eyes (4.66%) were ungradable. Among the 3,679 gradable ones, 1,105 (30.04%) showed different degrees of DR (R1 to R3), and 126 (3.42%) maculopathy (M1). Any Age-Related Macular Degeneration was present in 387 eyes (10.52%), any optic disc and parapapillary area features suspect for glaucoma in 562 eyes (15.27%), any hypertensive retinopathy in 1,263 eyes (34.33%), vitreoretinal interface disease in 252 eyes (6.84%), myopic choroidopathy in 92 eyes (2.50%), disc pallor in 31 eyes (0.84%). Mean time was 5 min for screening, 2 min for grading. CONCLUSION: Teleretinography is a well-established, cost-effective procedure in DR screening. Along with increased attendance, locating a digital camera in a DC with a retina-specialist grader results in finding fundus pathologies also beyond DR, very similarly to fundus examination in an outpatient ophthalmic setting.

Assessment of peripapillary vessel density in acute non-arteritic anterior ischemic optic neuropathy.

PURPOSE: To assess the peripapillary perfusion in eyes with acute non-arteritic anterior ischemic optic neuropathy (NAION) using optical coherence tomography angiography (OCTA). METHODS: Twenty-five patients with unilateral acute NAION were included in this observational cross-sectional study. They were divided into two groups: group I (25 eyes) included eyes with acute NAION, and group II (25 eyes) included fellow normal eyes. Diagnosis of NAION was based on clinical examination and fluorescein angiography. OCTA (AngioVue, Optovue) was used to evaluate the optic nerve head perfusion and measure the peripapillary vessel density in all eyes included in the study. RESULTS: Fourteen male and 11 female patients with a mean age of 60.2 ± 3.5 years were included in this study. The mean duration of presentation was 4.3 ± 0.6 days. Mean BCVA was 0.13 ± 0.06 and 0.69 ± 0.18 in eyes with NAION and normal eyes, respectively (p < 0.001). The peripapillary vessel was significantly decreased in all eyes with NAION compared with normal ones (p < 0.001). Two morphological changes were noted in eyes with NAION: vascular dropout related to area of disc edema in 25 eyes (100% of eyes) and vascular dilatation with tortuosity in 17 eyes (68%). CONCLUSION: Eyes with NAION have decreased peripapillary vessel density with peripapillary vascular dilatation and tortuosity as assessed by OCTA.

Morphological assessment of lamina cribrosa in idiopathic intracranial hypertension.

Purpose: Technological development of optic coherence tomography has enabled a detailed assessment of the optic nerve and deeper structures and in vivo measurements. The aim of this study was to compare the lamina cribrosa morphology of the optic nerve in idiopathic intracranial hypertension (IIH) and healthy individuals. Methods: The lamina cribrosa morphology of optic nerve in 15 eyes with IIH and 17 eyes of healthy individuals were compared. Four parameters such as Bruch membrane opening (BMO), lamina cribrosa thickness (LCT), prelaminar tissue thickness (PTT), and anterior lamina cribrosa surface depth (ALCSD) were retrospectively evaluated. Results: By enhanced depth imaging-optic coherence tomography (EDI-OCT), PTT and BMO were found to be significantly greater (574,35 ± 169,20 µm and 1787,40 ± 140,87 µm, respectively) in IIH patients than healthy individuals (187,18 ± 132,15 µm and 1632,65 ± 162,58 µm, respectively), whereas ALSCD was found to be significantly less in IIH patients (234,49 ± 49,31 µm) than healthy individuals (425,65 ± 65,23 µm). There was not a statistically significant difference regarding LCT between the IIH patients (238,59 ± 17,31 µm) and healthy individuals (244,96 ± 15,32 µm). Conclusion: Increased intracranial pressure causes morphological changes in lamina cribrosa. Assessment of lamina cribrosa with EDI-OCT is important for diagnosis and follow-up of patients with IIH. EDI-OCT is objective, reproducible, and cost-effective assistive imaging tool in IIH patients.

Evaluation of an AI system for the automated detection of glaucoma from stereoscopic optic disc photographs: the European Optic Disc Assessment Study.

OBJECTIVES: To evaluate the performance of a deep learning based Artificial Intelligence (AI) software for detection of glaucoma from stereoscopic optic disc photographs, and to compare this performance to the performance of a large cohort of ophthalmologists and optometrists. METHODS: A retrospective study evaluating the diagnostic performance of an AI software (Pegasus v1.0, Visulytix Ltd., London UK) and comparing it with that of 243 European ophthalmologists and 208 British optometrists, as determined in previous studies, for the detection of glaucomatous optic neuropathy from 94 scanned stereoscopic photographic slides scanned into digital format. RESULTS: Pegasus was able to detect glaucomatous optic neuropathy with an accuracy of 83.4% (95% CI: 77.5-89.2). This is comparable to an average ophthalmologist accuracy of 80.5% (95% CI: 67.2-93.8) and average optometrist accuracy of 80% (95% CI: 67-88) on the same images. In addition, the AI system had an intra-observer agreement (Cohen's Kappa, κ) of 0.74 (95% CI: 0.63-0.85), compared with 0.70 (range: -0.13-1.00; 95% CI: 0.67-0.73) and 0.71 (range: 0.08-1.00) for ophthalmologists and optometrists, respectively. There was no statistically significant difference between the performance of the deep learning system and ophthalmologists or optometrists. CONCLUSION: The AI system obtained a diagnostic performance and repeatability comparable to that of the ophthalmologists and optometrists. We conclude that deep learning based AI systems, such as Pegasus, demonstrate significant promise in the assisted detection of glaucomatous optic neuropathy.

Swept-Source OCT for Evaluating the Lamina Cribrosa: A Report by the American Academy of Ophthalmology.

PURPOSE: To review the published literature on the use of swept-source (SS) OCT for evaluating the lamina cribrosa in glaucoma. METHODS: A PubMed and Cochrane Library literature search initially conducted on March 3, 2017, and updated on June 26, 2018, yielded a total of 64 articles. Articles that were reviews or that were not published in English were excluded, and 29 were found to fit the inclusion criteria. The panel methodologist then assigned a level of evidence rating to each study. Fifteen studies were rated level III, 14 studies were rated level II, and no studies were rated level I. RESULTS: Different aspects of the lamina cribrosa were studied using SS-OCT, including the anterior lamina cribrosa curvature, anterior lamina cribrosa depth, anterior lamina cribrosa insertions, laminar thickness, focal lamina cribrosa defects (FLCDs), and lamina cribrosa microarchitecture. In general, imaging of the anterior lamina can be achieved reliably, although shadowing from blood vessels at the neuroretinal rim remains an issue. Imaging of the posterior lamina can be achieved with varying levels of success. In glaucoma, there is posterior migration of the anterior lamina cribrosa insertions as well as increased thinning and posterior curvature of the lamina cribrosa. Focal lamina cribrosa defects appear more commonly in glaucoma, and this may hint at the pathogenesis of axonal damage. In addition, there may be remodeling of the microarchitecture of the lamina, resulting in more variable laminar pores. There are limited studies comparing SS-OCT with spectral-domain (SD) OCT with regard to imaging of the lamina, but the difference in image quality between enhanced depth imaging (EDI) with SD-OCT and SS-OCT seems minimal. CONCLUSIONS: Imaging of the lamina cribrosa using SS-OCT has demonstrated that the lamina cribrosa is likely biomechanically active and that significant changes occur in glaucoma. The diagnostic utility of SS-OCT for lamina cribrosa imaging is promising, but standardized nomenclature, automated measurements, and longitudinal studies with larger and more diverse sample sizes are needed.

Comparison of Spectralis and Cirrus spectral domain optical coherence tomography for the objective morphometric assessment of the neuroretinal rim width.

PURPOSE: The assessment of cup-disc ratio as a surrogate parameter for the neuroretinal rim width (NRW) of the optic nerve is well established, but prone to human error and imprecision. Objective assessment of the NRW is provided by spectral domain optical coherence tomography (SD-OCT). This study is the first to systematically compare NRW measurements acquired with the Carl Zeiss Meditech Cirrus HD-OCT 5000 and the Heidelberg Engineering Spectralis SD-OCT. METHODS: In this cross-sectional study, 20 eyes of each 20 glaucoma patients and 20 age-matched healthy controls underwent ophthalmic examination, SD-OCT imaging, and computer perimetry. Regression analyses were performed for the NRW comparability and the effect of the rotational alignment disconcordance (RAD), receiver-operating characteristics (ROC) for NRW-based healthy glaucoma discrimination capability, and Pearson's correlation for covariate association. RESULTS: Mean NRW differences were 8 ± 48 µm (p = 0.4528), 91 ± 80 µm (p < 0.01), and 49 ± 77 µm (p < 0.001) in the glaucoma, healthy, and whole group. On average, the Cirrus showed higher NRW values (+ 50 µm) than the Spectralis, this difference increased with values starting with 159 µm. Discrimination ROC were 1.0 (Spectralis) and 0.9675 (Cirrus). RAD showed very little effect on NRW (R2 = 0.9661, p < 0.001). NRW-covariate correlation was highly significant (p < 0.001) with both devices for clinical cup/disc ratio, calculated rim width, visual field mean, and pattern deviations. CONCLUSIONS: Our results suggest to only cautiously compare Spectralis and Cirrus NRW measurements only in patients with morphologically manifest glaucoma. For morphological progression analysis, we recommend the continuous usage of the same device.

Detecting Glaucoma Progression Using Guided Progression Analysis with OCT and Visual Field Assessment in Eyes Classified by International Classification of Disease Severity Codes.

PURPOSE: To compare the detection and rates of progressive retinal nerve fiber layer (RNFL) and ganglion cell-inner plexiform layer (GCIPL) loss with spectral-domain (SD) OCT and visual field (VF) loss using Guided Progression Analysis (GPA; Carl Zeiss Meditec, Dublin, CA) in glaucomatous eyes classified using International Classification of Diseases (ICD) diagnosis codes. DESIGN: Retrospective cohort study. PARTICIPANTS: Glaucoma patients with at least 3 years of follow-up and a minimum of 4 SD OCT and 5 reliable VF examinations. METHODS: Glaucoma severity was classified using ICD, 10th Edition, Clinical Modification, diagnosis codes. Rates of RNFL, macular GCIPL, and VF loss were calculated, and progression estimates were compared using generalized estimating equations and McNemar's tests. MAIN OUTCOME MEASURES: Progressive RNFL, GCIPL, and VF loss assessed by GPA criteria. RESULTS: A total of 147 eyes of 116 patients (mean age, 69.9±8.5 years) were included with mean follow-up of 69.67±18.64 months. Overall, 38 of 147 eyes (25.9%) showed RNFL progression, 35 eyes (23.8%) showed GCIPL progression, and 20 eyes (13.6%) showed VF progression. Progression by all 3 methods was noted in 10 eyes (7.0%). Eyes with mild (n = 62) and severe (n = 46) glaucoma showed significantly more progression on SD OCT compared with VF (P < 0.001 and P = 0.004). Retinal nerve fiber layer, GCIPL, and VF progressors showed faster rates of loss in average RNFL, GCIPL, and VF mean deviation compared with nonprogressors (mean ± standard error: -1.47±0.30 µm/year vs. -0.03±0.12 µm/year [P = 0.0001], -1.68±0.34 µm/year vs. -0.29±0.07 µm/year [P = 0.0001], and -1.07±0.20 dB/year vs. -0.19±0.04 dB/year [P = 0.0001], respectively). CONCLUSIONS: Spectral-domain OCT progression was significantly more common than VF progression in glaucomatous eyes classified with mild and severe disease. Structure and function should be monitored closely across the entire spectrum of glaucoma severity.

Assessment of the Impact of an Endpoint Committee in the Ocular Hypertension Treatment Study.

PURPOSE: To assess the impact of a masked Endpoint Committee on estimates of the incidence of primary open-angle glaucoma (POAG) treatment efficacy and statistical power of the Ocular Hypertension Treatment Study-Phase 1, 1994-2002 (OHTS-1). DESIGN: Retrospective interrater reliability analysis of endpoint attribution by the Endpoint Committee. METHODS: After study closeout, we recalculated estimates of endpoint incidence, treatment efficacy, and statistical power using all-cause endpoints and POAG endpoints. To avoid bias, only the first endpoint per participant is included in this report. RESULTS: The Endpoint Committee reviewed 267 first endpoints from 1636 participants. The Endpoint Committee attributed 58% (155 of 267) of the endpoints to POAG. The incidence of all-cause endpoints vs POAG endpoints was 19.5% and 13.2%, respectively, in the observation group and 13.1% and 5.8%, respectively, in the medication group. Treatment effect for all-cause endpoints was a 33% reduction in risk (relative risk = 0.67, 95% confidence interval [CI] of 0.54-0.84) and a 56% reduction in risk for POAG endpoints (relative risk = 0.44, 95% CI of 0.31-0.61). Post hoc statistical power for detecting treatment effect was 0.94 for all-cause endpoints and 0.99 for POAG endpoints. CONCLUSION: Endpoint Committee adjudication of endpoints improved POAG incidence estimates, increased statistical power, and increased calculated treatment effect by 23%. An Endpoint Committee should be considered in therapeutic trials when common ocular and systemic comorbidities, other than the target condition, could compromise study results.

Prevalence of optic disc haemorrhages in an elderly UK Caucasian population and possible association with reticular pseudodrusen-the Bridlington Eye Assessment Project (BEAP): a cross-sectional study (2002-2006).

AIMS: To determine disc haemorrhage (DH) prevalence in an elderly UK population-the Bridlington Eye Assessment Project (BEAP). METHODS: Thirty-degree fundus photographs (3549 participants ≥65 years) were graded for DH/macula changes. Glaucoma evaluation included Goldmann tonometry, 26-point suprathreshold visual-fields and mydriatic slit-lamp assessment for glaucomatous optic neuropathy. RESULTS: In all, 3548 participants with photographs in at least one eye. DHs were present in 53 subjects (1.49%), increasing from 1.17% (65- to 69-year age group) to 2.19% (80- to 84-year age group), p = 0.06. DH was found in 9/96 (9.38%) right eyes (RE) with open-angle glaucoma (OAG). Two of twelve RE (16.67%) with normal-tension glaucoma (NTG) had DH. Prevalence in eyes without glaucoma was lower (32/3452, [0.93%]). Reticular pseudodrusen (RPD) occurred in 170/3212 (5.29%) subjects without DH, and 8/131 subjects (6.11%) with OAG. Twenty eyes had NTG, two of whom had RPD (10%) (p = 0.264). Within a logistic regression model, DH was associated with glaucoma (OR 10.2, 95% CI 5.32-19.72) and increasing age (OR 1.05, 95% CI 1.00-1.10, p = 0.03). DH was associated with RPD (p = 0.05) with univariate analysis but this was not statistically significant in the final adjusted model. There was no significant association with gender, diabetes mellitus (DM), hypertension treatment or Age-related Macular Degeneration (AMD) grade. CONCLUSION: DH prevalence is 1.5% in those over 65 years old and significantly associated with glaucoma and increasing age. There appears to be increased RPD prevalence in eyes with DH and NTG with age acting as a confounding factor. Larger studies are required to fully assess the relationship and investigate a possible shared aetiology of choroidal ischaemia.

Clinical Prediction Performance of Glaucoma Progression Using a 2-Dimensional Continuous-Time Hidden Markov Model with Structural and Functional Measurements.

PURPOSE: Previously, we introduced a state-based 2-dimensional continuous-time hidden Markov model (2D CT HMM) to model the pattern of detected glaucoma changes using structural and functional information simultaneously. The purpose of this study was to evaluate the detected glaucoma change prediction performance of the model in a real clinical setting using a retrospective longitudinal dataset. DESIGN: Longitudinal, retrospective study. PARTICIPANTS: One hundred thirty-four eyes from 134 participants diagnosed with glaucoma or as glaucoma suspects (average follow-up, 4.4±1.2 years; average number of visits, 7.1±1.8). METHODS: A 2D CT HMM model was trained using OCT (Cirrus HD-OCT; Zeiss, Dublin, CA) average circumpapillary retinal nerve fiber layer (cRNFL) thickness and visual field index (VFI) or mean deviation (MD; Humphrey Field Analyzer; Zeiss). The model was trained using a subset of the data (107 of 134 eyes [80%]) including all visits except for the last visit, which was used to test the prediction performance (training set). Additionally, the remaining 27 eyes were used for secondary performance testing as an independent group (validation set). The 2D CT HMM predicts 1 of 4 possible detected state changes based on 1 input state. MAIN OUTCOME MEASURES: Prediction accuracy was assessed as the percentage of correct prediction against the patient's actual recorded state. In addition, deviations of the predicted long-term detected change paths from the actual detected change paths were measured. RESULTS: Baseline mean ± standard deviation age was 61.9±11.4 years, VFI was 90.7±17.4, MD was -3.50±6.04 dB, and cRNFL thickness was 74.9±12.2 µm. The accuracy of detected glaucoma change prediction using the training set was comparable with the validation set (57.0% and 68.0%, respectively). Prediction deviation from the actual detected change path showed stability throughout patient follow-up. CONCLUSIONS: The 2D CT HMM demonstrated promising prediction performance in detecting glaucoma change performance in a simulated clinical setting using an independent cohort. The 2D CT HMM allows information from just 1 visit to predict at least 5 subsequent visits with similar performance.