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 < 0.001 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.

Reverse translation of artificial intelligence in glaucoma: Connecting basic science with clinical applications.

Artificial intelligence (AI) has been approved for biomedical research in diverse areas from bedside clinical studies to benchtop basic scientific research. For ophthalmic research, in particular glaucoma, AI applications are rapidly growing for potential clinical translation given the vast data available and the introduction of federated learning. Conversely, AI for basic science remains limited despite its useful power in providing mechanistic insight. In this perspective, we discuss recent progress, opportunities, and challenges in the application of AI in glaucoma for scientific discoveries. Specifically, we focus on the research paradigm of reverse translation, in which clinical data are first used for patient-centered hypothesis generation followed by transitioning into basic science studies for hypothesis validation. We elaborate on several distinctive areas of research opportunities for reverse translation of AI in glaucoma including disease risk and progression prediction, pathology characterization, and sub-phenotype identification. We conclude with current challenges and future opportunities for AI research in basic science for glaucoma such as inter-species diversity, AI model generalizability and explainability, as well as AI applications using advanced ocular imaging and genomic data.

Minimally Invasive Glaucoma Surgery in Primary Angle-Closure Glaucoma.

Primary angle-closure glaucoma (PACG) is responsible for half of the glaucoma-related blindness worldwide. Cataract surgery with or without trabeculectomy has been considered to be the first-line treatment in eyes with medically uncontrolled PACG. While minimally invasive glaucoma surgery has become an important surgical approach for primary open-angle glaucoma, its indications and benefits in PACG are less clear. This review summarizes the efficacy and safety profile of minimally invasive glaucoma surgery in PACG to unfold new insights into the surgical management of PACG.

Retinal Nerve Fiber Layer Optical Texture Analysis: Involvement of the Papillomacular Bundle and Papillofoveal Bundle in Early Glaucoma.

PURPOSE: To apply retinal nerve fiber layer (RNFL) optical texture analysis (ROTA) in eyes with early glaucoma to investigate (1) the pattern of RNFL defects, (2) how often the papillomacular bundle and papillofoveal bundles are involved, and (3) the association between papillomacular and papillofoveal bundle defects and visual field (VF) sensitivity abnormalities. DESIGN: Cross-sectional study. PARTICIPANTS: Two hundred four eyes with early glaucoma (VF mean deviation, ≥ -6 dB) with RNFL defects from 171 consecutively enrolled patients with glaucoma. METHODS: All eyes underwent 24-2 VF testing and OCT for ROTA. The borders of RNFL defects were delineated from ROTA, and the involvement of the arcuate bundle, papillomacular bundle (i.e., bundles from the macula, excluding the fovea), and papillofoveal bundle (i.e., bundles from the fovea) was determined for each eye. Multilevel logistic regression analysis was applied to evaluate the structure-function association. MAIN OUTCOME MEASURES: Proportions of eyes with papillomacular or papillofoveal bundle defects. RESULTS: Of the 204 eyes, 71.6% and 17.2% demonstrated RNFL defects involving the papillomacular and papillofoveal bundles, respectively; 25.0% showed arcuate bundle defects without involvement of papillomacular or papillofoveal bundles. The pattern of RNFL defects was diverse; the most common was concomitant involvement of the inferior arcuate bundle and the inferior papillomacular bundle (20.6%). Papillomacular or papillofoveal bundle defects were not associated with VF defects (i.e., with ≥ 3 contiguous locations with abnormal VF sensitivity in the pattern deviation probability plot) in the corresponding hemifield, although VF sensitivity of any 1 of the central 4 VF locations of the 24-2 test, which were within the macula, was more likely to be abnormal (P < 0.05 in the pattern deviation probability plot; odds ratio, 12.5; 95% confidence interval, 7.0-22.5) when the VF stimulus was projected onto a papillomacular or papillofoveal bundle defect than that projected onto an intact papillomacular or papillofoveal bundle. CONCLUSIONS: Contrary to the conventional notion that the fovea and macula are not affected until the late stages of glaucoma, papillofoveal and papillomacular bundle defects were common in early glaucoma, and they were associated with central VF sensitivity loss at the corresponding VF test locations.

Comparison of two novel swept-source optical coherence tomography devices to a partial coherence interferometry-based biometer.

To evaluate the repeatability and agreement of corneal and biometry measurements obtained with two swept-source optical coherence tomography (SSOCT) and a partial coherence interferometry-based device. This is a cross-sectional study. Forty-eight eyes of 48 patients had three consecutive measurements for ANTERION (Heidelberg Engineering, Germany), CASIAII (Tomey, Japan) and IOLMaster500 (Carl Zeiss Meditec, USA) on the same visit. Mean keratometry (Km), central corneal thickness (CCT), anterior chamber depth (ACD) and axial length (AL) were recorded. Corneal astigmatic measurements were converted into vector components-J0 and J45. Intra-device repeatability and agreements of measurements amongst the devices were evaluated using repeatability coefficients (RCs) and Bland-Altman plots, respectively. All devices demonstrated comparable repeatability for Km (p ≥ 0.138). ANTERION had the lowest RC for J0 amongst the devices (p ≤ 0.039). Systematic difference was found for the Km and J0 obtained with IOLMaster500 compared to either SSOCTs (p ≤ 0.010). The ACD and AL measured by IOLMaster500 showed a higher RC compared with either SSOCTs (p < 0.002). Systematic difference was found in CCT and ACD between the two SSOCTs (p < 0.001), and in AL between ANTERION and IOLMaster500 (p < 0.001), with a mean difference of 1.6 µm, 0.022 mm and 0.021 mm, respectively. Both SSOCTs demonstrated smaller test-retest variability for measuring ACD and AL compared with IOLMaster500. There were significant disagreement in keratometry and AL measurements between the SSOCTs and PCI-based device; their measurements should not be considered as interchangeable.

Clear lens extraction in eyes with primary angle closure and primary angle-closure glaucoma.

The crystalline lens plays an important role in the pathophysiology of primary angle closure and primary angle-closure glaucoma. The aging process is associated with a progressive enlargement of the lens, resulting in greater iridolenticular and iridotrabecular contact, which exacerbates both pupillary block and appositional angle closure, irrespective of the cataract status of the lens. Cataract surgery has been shown to widen the angle and reduce intraocular pressure in eyes with primary angle closure or primary angle-closure glaucoma. Recently, clear lens phacoemulsification has been suggested as a treatment modality in such eyes. We review the literature on clear lens extraction in eyes with angle closure and discuss its efficacy, safety, and indications. Although it is evident that clear lens extraction is beneficial in eyes with primary angle closure and primary angle-closure glaucoma, it is technically challenging and should be performed by experienced surgeons who not only master the procedure but are also able to deal with potential complications. Since the follow-up of the reviewed studies is relatively short, long-term follow-up (>10 years) of patients who undergo this procedure is needed to evaluate the safety and confirm the early benefits reported.

Association of the CAV1-CAV2 locus with normal-tension glaucoma in Chinese and Japanese.

BACKGROUND: The CAV1-CAV2 locus has been associated with primary open-angle glaucoma (POAG) and intraocular pressure. However, its association with normal-tension glaucoma (NTG) was inconclusive. Therefore, we evaluated this association in Chinese and Japanese. METHODS: Two single-nucleotide polymorphisms (SNPs, rs4236601 and rs1052990) from previous genome-wide association studies of POAG were genotyped in a total of 2220 study subjects: a Hong Kong Chinese cohort of 537 NTG patients and 490 controls, a Shantou Chinese cohort of 102 NTG and 731 controls and an Osaka Japanese cohort of 153 NTG and 207 controls. Subgroup analysis by gender was conducted. Outcomes from different cohorts were combined using meta-analysis. RESULTS: SNP rs4236601 was significantly associated with NTG in the two Chinese cohorts (Pmeta = .0019, OR = 4.55, I2 = 0). In contrast, rs4236601 was monomorphic in the Osaka cohort. The association of rs1052990 was insignificant in a meta-analysis combining Chinese and Japanese cohorts (Pmeta = .81, OR = 1.05; I2 = 64%), and the OR tended towards opposite directions between Chinese (OR = 1.26) and Japanese (OR = 0.69). Gender-specific effects of the SNPs were not statistically significant in the logistic regression or Breslow-day tests of ORs (P > .05), although rs4236601 was significant in males (P = .0068; OR = 10.30) but not in females (P = .14; OR = 2.65) in the meta-analysis of Chinese subjects. CONCLUSIONS: In this study, we confirmed the association of rs4236601 at the CAV1-CAV2 locus with NTG in Chinese. SNP rs4236601 is monomorphic, and rs1052990 tends towards a different direction in the Japanese cohort. Further studies are warranted to verify the ethnic difference and gender-specific effects of this locus.

Use of Virtual Reality Simulation to Identify Vision-Related Disability in Patients With Glaucoma.

Importance: Clinical assessment of vision-related disability is hampered by the lack of instruments to assess visual performance in real-world situations. Interactive virtual reality (VR) environments displayed in a binocular stereoscopic VR headset have been designed, presumably simulating day-to-day activities to evaluate vision-related disability. Objective: To investigate the application of VR to identify vision-related disability in patients with glaucoma. Design, Setting, and Participants: In a cross-sectional study, 98 patients with glaucoma and 50 healthy individuals were consecutively recruited from a university eye clinic; all participants were Chinese. The study was conducted between August 30, 2016, and July 31, 2017; data analysis was performed from December 1, 2017, to October 30, 2018. Exposures: Measurements of visual acuity, contrast sensitivity, visual field (VF), National Eye Institute 25-item Visual Function Questionnaire Rasch score, and VR disability scores determined from 5 VR simulations: supermarket shopping, stair and city navigations in daytime, and stair and city navigations in nighttime. Duration required to complete the simulation, number of items incorrectly identified, and number of collisions were measured to compute task-specific and overall VR disability scores. Vision-related disability was identified when the VR disability score was outside the normal age-adjusted 95% confidence region. Main Outcomes and Measures: Virtual reality disability score. Results: In the 98 patients with glaucoma, mean (SD) age was 49.8 (11.6) years and 60 were men (61.2%); in the 50 healthy individuals, mean (SD) age was 48.3 (14.8) years and 16 were men (32.0%). The patients with glaucoma had different degrees of VF loss (122 eyes [62.2%] had moderate or advanced VF defects). The time required to complete the activities by patients with glaucoma vs healthy individuals was longer by 15.2 seconds (95% CI, 5.5-24.9 seconds) or 34.1% (95% CI, 12.4%-55.7%) for the shopping simulation, 72.8 seconds (95% CI, 23.0-122.6 seconds) or 33.8% (95% CI, 10.7%-56.9%) for the nighttime stair navigation, and 38.1 seconds (95% CI, 10.9-65.2 seconds) or 30.8% (95% CI, 8.8%-52.8%) for the nighttime city navigation. The mean (SD) duration was not significantly different between the glaucoma and healthy groups in daytime stair (203.7 [93.7] vs 192.9 [89.1] seconds, P = .52) and city (118.7 [41.5] vs 117.0 [52.3] seconds, P = .85) navigation. For each decibel decrease in binocular VF sensitivity, the risk of collision increased by 15% in nighttime stair (hazard ratio [HR], 1.15; 95% CI, 1.08-1.22) and city (HR, 1.15; 95% CI, 1.08-1.23) navigations. Fifty-eight patients (59.1%) with glaucoma had vision-related disability in at least 1 simulated daily task; a higher proportion of patients had vision-related disability in nighttime city (27 of 88 [30.7%]) and stair (27 of 90 [30.0%]) navigation than in daytime city (7 of 88 [8.0%]) and stair (19 of 96 [19.8%]) navigation. The overall VR disability score was associated with the National Eye Institute 25-item Visual Function Questionnaire Rasch score (R2 = 0.207). Conclusions and Relevance: These findings suggest that vision-related disability is associated with lighting condition and task in patients with glaucoma. Virtual reality may allow eye care professionals to understand the patients' perspectives on how visual impairment imparts disability in daily living and provide a new paradigm to augment the assessment of vision-related disability.

Diagnostic Accuracy of Rapid Assessment of Avoidable Blindness: A Population-based Assessment.

OBJECTIVES: To evaluate the diagnostic accuracy of rapid assessment of avoidable blindness (RAAB). DESIGN: Population-based diagnostic accuracy study. METHODS: A total of 2145 (95.3%, 2145/2250) subjects aged 50 years and older who participated in the RAAB survey were included. All the recruited participants underwent ophthalmic examination according to the RAAB protocol and then were reexamined with instruments in a mobile eye clinic set up in a village center on the same day. Examination in the mobile clinic included standardized visual acuity (VA) tests using logMAR charts, refraction, slit-lamp biomicroscopy, and dilated fundal examination with a binocular indirect ophthalmoscope. Blindness and economic blindness were defined as VA in the better-seeing eye <3/60 and <6/60, respectively. Visual impairment (VI) was defined as VA <6/18 in the better eye. The primary cause of blindness and VI was defined according to the cause of VI in the participant's better eye. MAIN OUTCOME MEASURES: The sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), and area under the curve (AUC) of receiver operating characteristics of RAAB for detection of blindness and the principal causes of VI. RESULTS: A total of 1816 subjects (84.7%), including 686 men (37.8%) and 1130 women (62.2%), underwent ophthalmic examination in the mobile eye clinic. The mean (±standard deviation) age was 64.4 ± 9.6 years. The sensitivities, specificities, AUC, PLR, and NLR of RAAB were 90.3%, 99.3%, 0.948, 124.0, and 0.10, respectively, for detection of blindness (presenting visual acuity, PVA <3/60); 89.5%, 98.7%, 0.940, 69.2, and 0.11, respectively, for detection of economic blindness (PVA <6/60); and 90.3%, 97.7%, 0.940, 38.7, and 0.10, respectively, for detection of VI (PVA <6/18). The sensitivities, specificities, AUC, PLR, and NLR were 90.5%, 98.1%, 0.943, 48.1, and 0.10; and 60.4%, 98.7%, 0.796, 46.4, and 0.40 for detection of VI (PVA <6/18) owing to cataract and refractive error, respectively. CONCLUSION: The diagnostic performances of RAAB were high for detecting the prevalence of blindness, VI, and VI owing to cataract.

Intracameral injection of a chemically cross-linked hydrogel to study chronic neurodegeneration in glaucoma.

Investigation of neurodegeneration in glaucoma, a leading cause of irreversible blindness worldwide, has been obfuscated by the lack of an efficient model that provides chronic, mild to moderate elevation of intraocular pressure (IOP) with preservation of optical media clarity for long term, in vivo interrogation of the structural and functional integrity of the retinal ganglion cells (RGCs). Here, we designed and formulated an injectable hydrogel based on in situ cross-linking of hyaluronic acid functionalized with vinyl sulfone (HA-VS) and thiol groups (HA-SH). Intracameral injection of HA-VS and HA-SH in C57BL/6J mice exhibited mild to moderate elevation of IOP with daily mean IOP ranged between 14 ±â€¯3 and 24 ±â€¯3 mmHg, which led to progressive, regional loss of RGCs evaluated with in vivo, time-lapse confocal scanning laser ophthalmoscopy; a reduction in fractional anisotropy in the optic nerve and the optic tract projected from the eye with increased IOP in diffusion tensor magnetic resonance imaging; a decrease in positive scotopic threshold response in electroretinography; and a decline in visual acuity measured with an optokinetic virtual reality system. The proportion of RGC loss was positively associated with the age of the animals, and the levels and the duration of IOP elevation. The new glaucoma model recapitulates key characteristics of human glaucoma which is pertinent to the development and pre-clinical testing of neuroprotective and neuroregenerative therapies. STATEMENT OF SIGNIFICANCE: A new model to study chronic neurodegeneration in glaucoma has been developed via intracameral injection of a specifically designed hyaluronic acid functionalized with vinyl sulfone and thiol groups for cross-linking. Intracameral injection of the chemically cross-linked hydrogel generates mild to moderate IOP elevation, resulting in progressive degeneration of the retinal ganglion cells, optic nerve, and optic tract, and a decline in visual function. The model recapitulates the key features of neurodegeneration in human glaucoma, which will facilitate and expedite the development of neuroprotective and neuroregenerative therapies.

Factors governing the transduction efficiency of adeno-associated virus in the retinal ganglion cells following intravitreal injection.

Efficient transduction of the retinal ganglion cells (RGCs) is a prerequisite to maximize therapeutic outcomes in any form of gene therapy for optic neuropathies. Whereas subretinal injection of adeno-associated virus 2 (AAV2) has been well-characterized, the serotype, viral load, and promoter combinations that govern RGC transduction efficiency following intravitreal injection remains poorly understood. We evaluated the transduction efficiency of seven AAV2 serotypes (AAV2/1, AAV2/2, AAV2/4, AAV2/5, AAV2/6, AAV2/8, and AAV2/9) for the RGCs at 4 weeks following intravitreal injection in C57BL/6J mice. Intravitreal injection of 1 × 109 vg of AAV2/2 with eGFP driven by the CMV promoter attained a higher transduction efficiency for the RGCs (60.0 ± 4.2%) compared with the six other AAV2 serotypes with eGFP driven by the same promoter injected at the same viral load ( < 3.0%). Reporter driven by the CAG promoter had a lower transduction efficiency (up to 42.0 ± 5.8%) compared with that driven by the CMV reporter (60.0 ± 4.2%, p ≤ 0.024). There was a viral dose-dependent transduction effect of AAV2/2-CMV-eGFP and the transduction efficiency was 40.2 ± 3.9%, 16.6 ± 4.2%, and 2.6 ± 0.2% when the viral load decreased to 5 × 108 vg, 1 × 108 vg, and 1 × 107 vg, respectively. Optimizing viral serotype, viral load, and promoter construct of AAV2 is important to maximize transgene expression in RGC-targeted gene therapy.

Association of the SIX6 locus with primary open angle glaucoma in southern Chinese and Japanese.

The purpose of the study was to evaluate the association profiles of the SIX6 locus with primary open-angle glaucoma (POAG) in southern Chinese and Japanese. In this study, we tested single marker and haplotype-based associations of 11 tagging single nucleotide polymorphisms (SNPs) covering the SIX6 locus with POAG in a Hong Kong Chinese cohort (N = 1402). A novel SNP (i.e., rs12436579) and two SNPs (i.e., rs33912345 and rs10483727) from previous genome-wide association studies were further tested in a Chinese cohort from Shantou (N = 888) and a Japanese cohort from Osaka (N = 463). Results from the three cohorts were meta-analysed using a random-effect model. We found rs12436579, which has not been previously reported, was associated with POAG in Hong Kong and Shantou Chinese (Pcombined = 4.3 × 10-5, OR = 0.72, I2 = 0). Additionally, we replicated the association of one known SNP, rs33912345 (Pcombined = 0.0061, OR = 0.69, I2 = 45%), with POAG in the Chinese cohorts but not in the Japanese cohort (P > 0.6). Another known SNP, rs10483727, was nominally associated with POAG in the two Chinese cohorts (Pcombined = 0.017, OR = 0.70, I2 = 53%). All these three SNPs were significantly associated with POAG when the three cohorts were combined in meta-analysis (Pcombined<0.005). Furthermore, two haplotypes, C-C (Pcombined = 1.13 × 10-5, OR = 1.41, I2 = 0) and A-A (Pcombined = 0.045, OR = 0.68, I2 = 70%), defined by rs33912345-rs12436579 were associated with POAG in Chinese but not in Japanese. In conclusion, this study confirmed the association between two GWAS SNPs in SIX6 (rs33912345 and rs10483727) and POAG. Also, a SNP, rs12436579, not associated with POAG before, was found to be associated with POAG in Chinese. Further studies are warranted to elucidate the role of this novel SNP in POAG.

Detection of Bruch's Membrane Opening in Healthy Individuals and Glaucoma Patients with and without High Myopia.

PURPOSE: To determine the proportions of eyes with indiscernible Bruch's membrane opening (BMO) in glaucoma patients and healthy individuals with and without high myopia and to investigate factors contributing to indiscernible BMO. DESIGN: Cross-sectional study. PARTICIPANTS: Five hundred eyes from 315 participants, including 212 high myopic eyes (axial length [AL], ≥26 mm) from 80 glaucoma patients and 60 healthy individuals and 288 non-high myopic eyes (AL, <26 mm) from 96 glaucoma patients and 88 healthy individuals. METHODS: The optic disc was imaged by the Spectralis OCT (Heidelberg Engineering, Heidelberg, Germany) using 24 equally spaced radial B-scans. The BMO was located independently by 2 trained observers and was recorded as discernible or indiscernible over 48 meridians in each eye. The BMO of a meridian was determined to be indiscernible when both observers failed to identify its location. The agreement between the observers was evaluated with κ statistics. Factors associated with indiscernible BMO were identified with multivariable, multilevel logistic regression modeling. MAIN OUTCOME MEASURES: Proportions of eyes with indiscernible BMO and hazard ratios (HRs) of factors associated with indiscernible BMO. RESULTS: The agreement for assessment of BMO visibility between the observers was good (κ, 0.631; 95% confidence interval, 0.602-0.661). In the groups with and without high myopia, 32.1% and 8.2% of glaucomatous eyes had 1 or more meridians with indiscernible BMO, respectively. In the healthy eyes, the respective proportions were 28.0% and 3.9%. The proportions were significantly higher in eyes with high myopia compared to eyes without high myopia in the glaucoma group (P < 0.001) and the healthy group (P < 0.001). The temporal meridian, followed by the inferotemporal and superotemporal meridians, of the optic disc were the most frequent locations with indiscernible BMO. Increased AL, advanced glaucoma, ß parapapillary atrophy, and young age were associated with an increased HR of indiscernible BMO (P ≤ 0.032). CONCLUSIONS: A significant proportion of high myopic eyes have indiscernible BMO at the temporal, superotemporal, and inferotemporal meridians of the optic disc, which may compromise the measurement of neuroretinal rim in the diagnostic evaluation of glaucoma.

Optical coherence tomography angiography in glaucoma: a mini-review.

The advent of optical coherence tomography angiography (OCT-A) provides a new opportunity to visualize the retinal vasculature in a non-invasive and dye-free manner which may help identify vascular abnormalities in glaucoma. While a reduction in retinal and optic nerve head vessel densities and blood flow indexes measured by OCT-A has been demonstrated in patients with glaucoma in many studies, it is unclear whether OCT-A provides additional information for the detection and monitoring of glaucoma compared with OCT measurements such as retinal nerve fiber layer thickness, neuroretinal rim width, and ganglion cell inner plexiform layer thickness. Longitudinal studies are needed to elucidate whether vascular abnormalities detected by OCT-A are a cause or a consequence of optic nerve damage in glaucoma.

Impact of Rates of Change of Lamina Cribrosa and Optic Nerve Head Surface Depths on Visual Field Progression in Glaucoma.

Purpose: To investigate the impact of the rates of change of anterior lamina cribrosa surface depth (ALCSD) and optic nerve head surface depth (ONHSD) on visual field (VF) progression in glaucoma. Methods: One hundred forty-six eyes of 95 glaucoma patients had optical coherence tomography ONH imaging and VF testing at approximately 4-month intervals for greater than or equal to 5 years. Anterior lamina cribrosa surface depth and ONHSD were measured with reference to (1) Bruch's membrane opening (BMO), and (2) choroid-sclera interface (CSI). The rates of change of ALCSD and ONHSD of individual eyes were measured with linear regression analysis. The hazard ratios (HRs) of the rates of change of ALCSD/ONHSD for prediction of VF progression as per Early Manifest Glaucoma Trial criteria were determined by joint longitudinal and survival models. Results: Using the BMO reference, 23.3% and 28.1% of eyes showed a significant positive trend (posterior displacement), whereas 29.5% and 24.0% showed a significant negative trend (anterior displacement) of ALCSD and ONHSD, respectively. Using the CSI reference, the proportions with a significant negative trend decreased to 11.6% and 14.4%, respectively; and the proportions with a significant positive trend increased to 37.7% and 38.4%, respectively. The HRs of VF progression were 1.06 and 1.11 for each micrometer per year increase in the rates of change of ALCSDBMO and ONHSDBMO, respectively; and 1.07 and 1.09 for each micrometer per year increase in the rates of change of ALCSDCSI and ONHSDCSI, respectively. Conclusions: Identifying fast progressors of posterior ALCS/ONHS displacement is relevant to the management of glaucoma patients as they have a higher risk of VF progression.

Primary open-angle glaucoma.

Glaucoma is an optic neuropathy that is characterized by the progressive degeneration of the optic nerve, leading to visual impairment. Glaucoma is the main cause of irreversible blindness worldwide, but typically remains asymptomatic until very severe. Open-angle glaucoma comprises the majority of cases in the United States and western Europe, of which, primary open-angle glaucoma (POAG) is the most common type. By contrast, in China and other Asian countries, angle-closure glaucoma is highly prevalent. These two types of glaucoma are characterized based on the anatomic configuration of the aqueous humour outflow pathway. The pathophysiology of POAG is not well understood, but it is an optic neuropathy that is thought to be associated with intraocular pressure (IOP)-related damage to the optic nerve head and resultant loss of retinal ganglion cells (RGCs). POAG is generally diagnosed during routine eye examination, which includes fundoscopic evaluation and visual field assessment (using perimetry). An increase in IOP, measured by tonometry, is not essential for diagnosis. Management of POAG includes topical drug therapies and surgery to reduce IOP, although new therapies targeting neuroprotection of RGCs and axonal regeneration are under development.

Evaluation of a Myopic Normative Database for Analysis of Retinal Nerve Fiber Layer Thickness.

IMPORTANCE: Analysis of retinal nerve fiber layer (RNFL) abnormalities with optical coherence tomography in eyes with high myopia has been complicated by high rates of false-positive errors. An understanding of whether the application of a myopic normative database can improve the specificity for detection of RNFL abnormalities in eyes with high myopia is relevant. OBJECTIVE: To evaluate the diagnostic performance of a myopic normative database for detection of RNFL abnormalities in eyes with high myopia (spherical equivalent, -6.0 diopters [D] or less). DESIGN, SETTING, AND PARTICIPANTS: In this cross-sectional study, 180 eyes with high myopia (mean [SD] spherical equivalent, -8.0 [1.8] D) from 180 healthy individuals were included in the myopic normative database. Another 46 eyes with high myopia from healthy individuals (mean [SD] spherical equivalent, -8.1 [1.8] D) and 74 eyes from patients with high myopia and glaucoma (mean [SD] spherical equivalent, -8.3 [1.9] D) were included for evaluation of specificity and sensitivity. The 95th and 99th percentiles of the mean and clock-hour circumpapillary RNFL thicknesses and the individual superpixel thicknesses of the RNFL thickness map measured by spectral-domain optical coherence tomography were calculated from the 180 eyes with high myopia. Participants were recruited from January 2, 2013, to December 30, 2015. The following 6 criteria of RNFL abnormalities were examined: (1) mean circumpapillary RNFL thickness below the lower 95th or (2) the lower 99th percentile; (3) one clock-hour or more for RNFL thickness below the lower 95th or (4) the lower 99th percentile; and (5) twenty contiguous superpixels or more of RNFL thickness in the RNFL thickness map below the lower 95th or (6) the lower 99th percentile. MAIN OUTCOMES AND MEASURES: Specificities and sensitivities for detection of RNFL abnormalities. RESULTS: Of the 46 healthy eyes and 74 eyes with glaucoma studied (from 39 men and 38 women), the myopic normative database showed a higher specificity (63.0%-100%) than did the built-in normative database of the optical coherence tomography instrument (8.7%-87.0%) for detection of RNFL abnormalities across all the criteria examined (differences in specificities between 13.0% [95% CI, 1.1%-24.9%; P = .01] and 54.3% [95% CI, 37.8%-70.9%; P < .001]) except for the criterion of mean RNFL thickness below the lower 99th percentile, in which both normative databases had the same specificities (100%) but the myopic normative database exhibited a higher sensitivity (71.6% vs 86.5%; difference in sensitivities, 14.9% [95% CI, 4.6%-25.1%; P = .002]). CONCLUSIONS AND RELEVANCE: The application of a myopic normative database improved the specificity without compromising the sensitivity compared with the optical coherence tomography instrument's built-in normative database for detection of RNFL abnormalities in eyes with high myopia. Inclusion of myopic normative databases should be considered in optical coherence tomography instruments.