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Glaucoma is a result of irreversible damage to the retinal ganglion cells. While an early intervention could minimise the risk of vision loss in glaucoma, its asymptomatic nature makes it difficult to diagnose until a late stage. The diagnosis of glaucoma is a complicated and expensive effort that is heavily dependent on the experience and expertise of a clinician. The application of artificial intelligence (AI) algorithms in ophthalmology has improved our understanding of many retinal, macular, choroidal and corneal pathologies. With the advent of deep learning, a number of tools for the classification, segmentation and enhancement of ocular images have been developed. Over the years, several AI techniques have been proposed to help detect glaucoma by analysis of functional and/or structural evaluations of the eye. Moreover, the use of AI has also been explored to improve the reliability of ascribing disease prognosis. This review summarises the role of AI in the diagnosis and prognosis of glaucoma, discusses the advantages and challenges of using AI systems in clinics and predicts likely areas of future progress.

Purpose: To map the 3-dimensional (3D) strain of the optic nerve head (ONH) in vivo after intraocular pressure (IOP) lowering by trabeculectomy (TE) and to establish associations between ONH strain and retinal sensitivity.Design: Observational case series.Participants: Nine patients with primary open-angle glaucoma (POAG) and 3 normal controls.Methods: The ONHs of 9 subjects with POAG (pre-TE IOP: 25.3 +/- 13.9 mmHg; post-TE IOP: 11.8 +/- 8.6 mmHg) were imaged (1 eye per subject) using optical coherence tomography (OCT) (Heidelberg Spectralis, Heidelberg Engineering GmbH, Heidelberg, Germany) before (< 21 days) and after (< 50 days) TE. The imaging protocol was repeated for 3 controls in whom IOP was not altered. In each post-TE OCT volume, 4 tissues were manually segmented (prelamina, choroid, sclera, and lamina cribrosa [LC]). For each ONH, a 3D tracking algorithm was applied to both post-and pre-TE OCT volumes to extract IOP-induced 3D displacements at segmented nodes. Displacements were filtered, smoothed, and processed to extract 3D strain relief (the amount of tissue deformation relieved after TE). Strain relief was compared with measures of retinal sensitivity from visual field testing.Main Outcome Measures: Three-dimensional ONH displacements and strain relief.Results: On average, strain relief (averaged or effective component) in the glaucoma ONHs (8.6%) due to TE was higher than that measured in the normal controls (1.07%). We found no associations between the magnitude of IOP decrease and the LC strain relief (P > 0.05), suggesting biomechanical variability across subjects. The LC displaced posteriorly, anteriorly, or not at all. Furthermore, we found linear associations between retinal sensitivity and LC effective strain relief (P < 0.001; high strain relief associated with low retinal sensitivity).Conclusions: We demonstrate that ONH displacements and strains can be measured in vivo and that TE can relieve ONH strains. Our data suggest a wide variability in ONH biomechanics in the subjects examined in this study. We further demonstrate associations between LC effective strain relief and retinal sensitivity.

Despite recent advances, our understanding of the aetiological mechanisms underlying glaucoma remains incomplete. Heavy metals toxicity has been linked to the development of neurodegenerative diseases and various ocular pathologies. Given the similarities in pathophysiology between glaucoma and some neurodegenerative disorders, it is plausible that heavy metal toxicity may play a role in the development of glaucoma. Heavy metal exposure may be occupational, or through water or dietary contamination. In this report, we review mechanisms for systemic and neurotoxicity for arsenic, cadmium, chromium, cobalt, lead, mercury, and manganese, and weigh the evidence for an association between glaucoma and the accumulation of heavy metals either in ocular tissues or in the central nervous system.

The lamina cribrosa (LC) is believed to be the site of injury to retinal ganglion cell axons in glaucoma. The ability to visualise this structure has the potential to help increase our understanding of the disease and be useful in the early detection of glaucoma. While for many years the research on the LC was essentially dependent on histology and modelling, a number of recent advances in optical coherence tomography (OCT) have dramatically improved the ability to visualise the LC, such that it is now possible to image the LC in vivo in humans and animals. In this review, we highlight recent advances in OCT imaging of the LC, in the technology, processing and analysis, and discuss the impact that these will have on the ability to diagnose and monitor glaucoma, as well as to expand our understanding of its pathophysiology. With this manuscript, we aspire to share our excitement on the achievements and potential of recent developments as well as advise caution regarding the challenges that remain before imaging of the LC and optic nerve can be used routinely in clinical practice.

AimsTo evaluate long-term outcomes and complications of trabeculectomy for normal tension glaucoma (NTG) with contemporary surgical techniques.MethodsRetrospective consecutive, non-comparative case series of 131 eyes of 98 patients undergoing trabeculectomy between 2007 and 2013 in a dedicated NTG clinic. Data collected during routine clinical care were analysed. Assessment of clinical outcomes included intraocular pressure (IOP) reduction, bleb function, final visual acuity, evidence of glaucoma progression, postoperative complications and further surgical intervention. Surgical failure was defined as a failure to meet specified IOP-related criteria, the need to undergo further glaucoma surgery for raised IOP or loss of light perception vision. A further analysis was also performed which considered failure as glaucoma progression following surgery. Outcomes were evaluated using Kaplan–Meier life-table analysis.ResultsThe cumulative percentages of unqualified success as defined by a ≥30% reduction of IOP from baseline preoperative maximum (95% CI; IOP of all eyes: mean±SD) at 1, 2, 3 and 4 years after surgery were 91.1% (84.1% to 95.1%; 9.7±2.9 mm Hg), 74.1% (63.7% to 81.8%; 10.3±3.0 mm Hg), 64.8% (52.7% to 74.6%; 10.6±2.5 mm Hg) and 62.1% (49.3% to 72.6%; 10.2±2.1 mm Hg), respectively. At 2 years of follow-up there was no significant association between either previous cataract surgery or ethnicity and failure. Cumulative percentages of unqualified success at 4 years after surgery as defined by a filtering trabeculectomy bleb or absence of glaucoma progression were 91.6% (83.2% to 95.9%) and 92.3% (81.3% to 97.0%), respectively. Postoperative complications such as early (2.3%) and late (0.8%) hypotony were significantly lower than suggested by the current literature.ConclusionsTrabeculectomy in NTG patients undertaken using contemporary surgical techniques and intensive postoperative management is associated with more successful long-term outcomes and fewer complications than the currently available literature suggests.

AimTo investigate the determinants of lamina cribrosa depth (LCD) in healthy eyes of Chinese and Indian Singaporean adults.MethodsThe optic nerve head (ONH) of the right eye of 1396 subjects (628 Chinese and 768 Indian subjects) was imaged with optical coherence tomography (OCT, Spectralis, Heidelberg, Germany). LCD was defined as the distance from the Bruch’s membrane opening (LCD-BMO) or the peripapillary sclera (LCD-PPS) reference plane to the laminar surface. A linear regression model was used to evaluate the relationship between the LCD and its determinants.ResultsBoth LCDs were significantly different between the two races (LCD-BMO: 421.95 (95% CI 365.32 to 491.79) µm in Chinese vs 430.39 (367.46–509.81) µm in Indians, p=0.021; and LCD-PPS: 353.34 (300.98–421.45) µm in Chinese vs 376.76 (313.39–459.78) µm in Indians, p<0.001). In the multivariable regression analysis, the LCD-PPS of the whole cohort was independently associated with females (β=−31.93, p<0.001), Indians subjects (β=21.39, p=0.004) (Chinese as the reference), axial length (Axl) (β=−6.68, p=0.032), retinal nerve fibre layer thickness (RNFL) (β=0.71, p=0.019), choroidal thickness (ChT) (β=0.41, p<0.001), vertical cup disc ratio (VCDR) (β=24.42, p<0.001) and disc size (β=−60.75, p=0.001). For every 1 year older in age, the LCD-PPS was deeper on average by 1.95 µm in Chinese subjects (p=0.01) but there was no association in Indians subjects (p=0.851).ConclusionsThe LCD was influenced by age, gender, race, Axl, RNFL, ChT, VCDR and disc size. This normative LCD database may facilitate a more accurate assessment of ONH cupping using OCT in Asian populations.

AimsTo compare the shape of the anterior surface of the peripapillary sclera (PPS) between glaucoma and healthy subjects.Methods88 primary open angle glaucoma (POAG), 98 primary angle closure glaucoma (PACG) and 372 age-matched and gender-matched healthy controls were recruited in this study. The optic nerve head of one randomly selected eye of each subject was imaged with spectral domain optical coherence tomography. The shape of the PPS was measured through an angle defined between a line parallel to the nasal anterior PPS boundary and one parallel to the temporal side. A negative value indicated that the PPS followed an inverted v-shaped configuration (peak pointing towards the vitreous), whereas a positive value indicated that it followed a v-shaped configuration.ResultsThe mean PPS angle in normal controls (4.56±5.99°) was significantly smaller than that in POAG (6.60±6.37°, p=0.011) and PACG (7.90±6.87°, p<0.001). The v-shaped PPS was significantly associated with older age (β=1.79, p<0.001), poorer best-corrected visual acuity (β=3.31, p=0.047), central corneal thickness (β=−0.28, p=0.001), peripapillary choroidal thickness (β=−0.21, p<0.001) and presence of POAG (β=1.94, p<0.009) and PACG (β=2.96, p<0.001). The v-shaped configuration of the PPS significantly increased by 1.46° (p=0.001) in healthy controls for every 10-year increase in age, but not in glaucoma groups.ConclusionsThe v-shaped configuration of the PPS was more pronounced in glaucoma eyes than in healthy eyes. This posterior bowing of the PPS may have an impact on the biomechanical environment of the optic nerve head.

This study was designed to evaluate if primary open angle glaucoma (POAG) and its severity are associated with the shape of the lamina cribrosa (LC) as measured by a global shape index (LC-GSI), or other indices of LC curvature or depth. Optical coherence tomography (OCT) scans of the optic nerve head (OHN) were obtained from subjects with POAG (n = 99) and non-glaucomatous controls (n = 76). ONH structures were delineated, the anterior LC morphology reconstructed in 3D, and the LC-GSI calculated (more negative values denote greater posterior concavity). Anterior LC depth and 2D-curvature were also measured. Severity of glaucoma was defined by the extent of visual field loss, based on the Hodapp-Parrish-Anderson grading. Linear regression analyses compared LC characteristics between controls, mild-moderate, and advanced POAG groups. After adjusting for age, gender, ethnicity, intraocular pressure, axial length and corneal curvature, the LC-GSI was most negative in the advanced POAG group (mean [standard error] = −0.34 [0.05]), followed by the mild-moderate POAG group (−0.31 [0.02]) and then controls (−0.23 [0.02], P Trend  = 0.01). There was also a significant trend of increasing LC depth and greater LC horizontal curvature with increasing severity of glaucoma ( P Trend  = 0.04 and 0.02, respectively). Therefore, with more severe glaucoma, the LC-GSI was increasingly more negative, and the anterior LC depth and curvature greater. These observations collectively correspond to greater cupping of the ONH at the level of the LC. As the LC-GSI describes the 3D anterior LC morphology, its potential usage may be complementary to existing ONH parameters measured on OCT.

BackgroundTo estimate and compare changes in the Bruch’s membrane opening—minimum rim width (BMO–MRW) and area in normal, ocular hypertensive and glaucoma eyes following acute elevations in intraocular pressure (IOP).MethodsThe optic nerve heads (ONHs) of 104 subjects (31 normals, 20 ocular hypertension (OHT) and 53 with primary glaucoma) were imaged using Spectral-domain optical coherence tomography (OCT; Spectralis, Heidelberg Engineering, Germany). IOP was raised twice by applying a force (0.64 n then 0.9 n) to the anterior sclera using an ophthalmo-dynamometer. After each IOP increment, IOP was held constant, measured with a Tonopen (AVIA applanation tonometer, Reichert, Depew, New York, USA), and ONH was rescanned with OCT. In each OCT volume, BMO–MRW and area were calculated and at each IOP increment.ResultsThe baseline MRW was significantly smaller in glaucoma subjects (174.3±54.3 µm) compared with normal (287.4±42.2 µm, p<0.001) and OHT subjects (255.4±45.3 µm, p<0.001). MRW of glaucoma subjects was significantly thinner at the first and second IOP elevations than that at baseline (both p<0.01), but no significant change was noted in normal and OHT subjects. There was no significant change of BMO area at acute IOP elevations from baseline in all diagnoses (all p>0.05).ConclusionAcute IOP elevation leads to compression of the nerve fibre layers of neuroretinal rim in glaucoma subjects only without changing ONH size. This suggests that the neural and connective tissues at ONH level in glaucoma subjects are more susceptible to acute IOP episodes than OHT or normal controls.