AN ASSOCIATION BETWEEN STELLATE NONHEREDITARY IDIOPATHIC FOVEOMACULAR RETINOSCHISIS, PERIPHERAL RETINOSCHISIS, AND POSTERIOR HYALOID ATTACHMENT.

PURPOSE: Stellate nonhereditary idiopathic foveomacular retinoschisis is a disorder characterized by splitting of the retina at the macula, without a known underlying mechanical or inherited cause. This study investigates demographic, anatomical, and functional characteristics of subjects with stellate nonhereditary idiopathic foveomacular retinoschisis, to explore potential underlying mechanisms. METHODS: In this single-site, retrospective, and cross-sectional, observational study, data were collected from 28 eyes from 24 subjects with stellate nonhereditary idiopathic foveomacular retinoschisis. Descriptive statistics were reported, based on the observed anatomico-functional features. RESULTS: The visual acuity remained stable (median 20/20) in all subjects over a median follow-up of 17 months. All cases demonstrated foveomacular retinoschisis within Henle's fiber layer, at the junction of the outer plexiform and outer nuclear layers. This schisis cavity extended beyond the limits of the macular OCT temporally in all eyes. In most affected eyes, there were documented features of peripheral retinoschisis and broad attachment of the posterior hyaloid at the macula. Functional testing in a cross-sectional subset demonstrated normal retinal sensitivity centrally but an absolute scotoma peripherally. CONCLUSION: Stellate nonhereditary idiopathic foveomacular retinoschisis seems to be associated with peripheral retinoschisis and anomalous or incomplete posterior hyaloid detachment. Despite chronic manifestation, this does not significantly affect central visual function but can manifest with profound loss of peripheral visual function.

Unpaired intra-operative OCT (iOCT) video super-resolution with contrastive learning.

Regenerative therapies show promise in reversing sight loss caused by degenerative eye diseases. Their precise subretinal delivery can be facilitated by robotic systems alongside with Intra-operative Optical Coherence Tomography (iOCT). However, iOCT's real-time retinal layer information is compromised by inferior image quality. To address this limitation, we introduce an unpaired video super-resolution methodology for iOCT quality enhancement. A recurrent network is proposed to leverage temporal information from iOCT sequences, and spatial information from pre-operatively acquired OCT images. Additionally, a patchwise contrastive loss enables unpaired super-resolution. Extensive quantitative analysis demonstrates that our approach outperforms existing state-of-the-art iOCT super-resolution models. Furthermore, ablation studies showcase the importance of temporal aggregation and contrastive loss in elevating iOCT quality. A qualitative study involving expert clinicians also confirms this improvement. The comprehensive evaluation demonstrates our method's potential to enhance the iOCT image quality, thereby facilitating successful guidance for regenerative therapies.

Intraoperative subconjunctival steroid reduces the incidence of pseudophakic macular oedema: a cohort study of 20,066 consecutive phacoemulsification surgeries.

BACKGROUND/OBJECTIVES: Pseudophakic macular oedema remains the most common sight-threatening complication following cataract surgery. This study aims to assess the effect of intraoperative subconjunctival steroids on the rate of pseudophakic cystoid macular oedema. METHODS: A retrospective, observational database study of 20 066 consecutive phacoemulsification surgeries. The incidence of pseudophakic cystoid macular oedema was compared in eyes that did and did not receive intraoperative subconjunctival steroid injection during routine cataract surgery. RESULTS: Intraoperative subconjunctival injection of dexamethasone or betamethasone sodium phosphate significantly reduced the odds of developing pseudophakic cystoid macular oedema across the cohort (odds ratio: 0.67; 95% confidence interval: 0.46-0.98, p = 0.039). The effect of subconjunctival steroids on pseudophakic macular oedema remained independently associated on multivariate logistic regression analysis (p = 0.028). CONCLUSION: This study demonstrates that administration of intraoperative subconjunctival steroid injection is associated with a reduced incidence of pseudophakic cystoid macular oedema in routine, uncomplicated cataract surgery.

Safety profile and surgical outcomes of early vitrectomy in eyes with unexplained fundus-obscuring vitreous haemorrhage.

OBJECTIVES: To investigate the safety profile and the surgical outcomes in a large cohort of subjects undergoing early vitrectomy for unexplained fundus-obscuring vitreous haemorrhage (FOVH). METHODS: Retrospective, single-centre case series of 186 consecutive eyes presenting between January 2018 and February 2020. Primary outcomes included change in best-corrected visual acuity (BCVA), rate of intra-operative retinal tears or retinal detachment (RD), baseline proliferative vitreoretinopathy (PVR), association of demographics with clinical outcomes, and rate of significant adverse events characterised by reoperation. RESULTS: Main final diagnosis was haemorrhagic posterior vitreous detachment (76%) and the overall risk of a retinal tear with or without RD found at the time of surgery was 69%. Vitrectomy was completed within 24 h in 94% of eyes. Rate of RD was 18%; all cases were macula-sparing with no PVR. Mean change in BCVA from baseline to final follow-up was -1.53 ± 0.69 LogMAR, p < 0.001. Time from presentation to surgery was significantly associated with final BCVA (p = 0.036, beta co-efficient 0.097). There was a significant association between presence of RD and age <60 y (OR 0.94, 95%CI [0.90-0.98], p = 0.003). 4.8% required repeated vitrectomy for post-operative RD (4), epiretinal membrane formation (3), removal of oil (1), and recurrent FOVH (1). None of these reoperations were induced by complications during the first surgery. CONCLUSION: There is a high rate of retinal breaks in cases with unexplained FOVH, and the risk of a concomitant RD is higher in younger subjects. Early vitrectomy within 24 h appears a safe first-line treatment and yields good clinical outcomes.

Normobaric hypoxia impairs human cardiac energetics.

Hypoxia causes left ventricular dysfunction in the human heart, but the biochemical mechanism is poorly understood. Here, we tested whether short-term normobaric hypoxia leads to changes in cardiac energetics and early cardiac dysfunction. Healthy male volunteers (n=12, age 24 ± 2 yr) were exposed to normobaric hypoxia in a purpose-built hypoxic chamber. The partial pressure of oxygen during end-tidal expiration (P(ET)o2) was kept between 50 and 60 mmHg, and peripheral oxygen saturation (Sao2) was kept above 80%. Cardiac morphology and function were assessed using magnetic resonance imaging and echocardiography, both before and after 20 h of hypoxic exposure, and high-energy phosphate metabolism [measured as the phosphocreatine (PCr)/ATP ratio] was measured using ³¹P magnetic resonance spectroscopy. During hypoxia, P(ET)o2 and Sao2 averaged 55 ± 1 mmHg and 83.6 ± 0.4%, respectively. Hypoxia caused a 15% reduction in cardiac PCr/ATP (from 2.0 ± 0.1 to 1.7 ± 0.1, P<0.01) and reduced diastolic function (measured as E/E', rising from 6.1 ± 0.4 to 7.5 ± 0.7, P<0.01). Normobaric hypoxia causes a rapid decrease in high-energy phosphate metabolism in the human cardiac left ventricle, which may lead to a decline in diastolic function. These findings are important in understanding the response of normal individuals to environmental hypoxia, and to situations in which disease reduces cardiac oxygen delivery.

Surgical biomicroscopy-guided intra-operative optical coherence tomography (iOCT) image super-resolution.

PURPOSE: Intra-retinal delivery of novel sight-restoring therapies will require the precision of robotic systems accompanied by excellent visualisation of retinal layers. Intra-operative Optical Coherence Tomography (iOCT) provides cross-sectional retinal images in real time but at the cost of image quality that is insufficient for intra-retinal therapy delivery.This paper proposes a super-resolution methodology that improves iOCT image quality leveraging spatiotemporal consistency of incoming iOCT video streams. METHODS: To overcome the absence of ground truth high-resolution (HR) images, we first generate HR iOCT images by fusing spatially aligned iOCT video frames. Then, we automatically assess the quality of the HR images on key retinal layers using a deep semantic segmentation model. Finally, we use image-to-image translation models (Pix2Pix and CycleGAN) to enhance the quality of LR images via quality transfer from the estimated HR domain. RESULTS: Our proposed methodology generates iOCT images of improved quality according to both full-reference and no-reference metrics. A qualitative study with expert clinicians also confirms the improvement in the delineation of pertinent layers and in the reduction of artefacts. Furthermore, our approach outperforms conventional denoising filters and the learning-based state-of-the-art. CONCLUSIONS: The results indicate that the learning-based methods using the estimated, through our pipeline, HR domain can be used to enhance the iOCT image quality. Therefore, the proposed method can computationally augment the capabilities of iOCT imaging helping this modality support the vitreoretinal surgical interventions of the future.

Dense laser at the papillomacular bundle does not cause loss of visual function.

INTRODUCTION: Juxtapapillary laser (JPL) photocoagulation in the region of the papillomacular bundle, temporal to the optic nerve, has become routine care in disorders such as optic disc pit maculopathy. Despite evidence demonstrating safe and effective use of this approach, there is still a lack of consensus in the literature, due to the perceived risk of loss of visual function. Instances of such misplaced caution could result in inadequate treatment protocols. METHODS: An observational series of five cases of optic disc pit maculopathy, treated with dense temporal juxtapapillary endolaser, in a single tertiary ophthalmic hospital. RESULTS: None of the reported cases of optic disc pit maculopathy treated with dense juxtapapillary laser demonstrated anatomical or perimetric findings consistent with nerve fiber layer damage in the region of the papillomacular bundle. CONCLUSIONS: This series demonstrates that dense laser photocoagulation, in the vicinity of the papillomacular bundle, does not cause structural damage to the nerve fiber layer or associated loss of visual function in optic disc pit maculopathy. Appropriate application of juxtapapillary laser is a safe and effective treatment for various macular pathologies.

Structural and Functional Characteristics of Color Vision Changes in Choroideremia.

Color vision is considered a marker of cone function and its assessment in patients with retinal pathology is complementary to the assessments of spatial vision [best-corrected visual acuity (BCVA)] and contrast detection (perimetry). Rod-cone and chorioretinal dystrophies-such as choroideremia-typically cause alterations to color vision, making its assessment a potential outcome measure in clinical trials. However, clinical evaluation of color vision may be compromised by pathological changes to spatial vision and the visual field. The low vision Cambridge Color Test (lvCCT) was developed specifically to address these latter issues. We used the trivector version of the lvCCT to quantify color discrimination in a cohort of 53 patients with choroideremia. This test enables rapid and precise characterization of color discrimination along protan, deutan, and tritan axes more reliably than the historically preferred test for clinical trials, namely the Farnsworth Munsell 100 Hue test. The lvCCT demonstrates that color vision defects-particularly along the tritan axis-are seen early in choroideremia, and that this occurs independent of changes in visual acuity, pattern electroretinography and ellipsoid zone area on optical coherence tomography (OCT). We argue that the selective loss of tritan color discrimination can be explained by our current understanding of the machinery of color vision and the pathophysiology of choroideremia.

Phacoemulsification Combined With Endoscopic Versus Transscleral Cyclophotocoagulation in Poorly Controlled Glaucoma: A Comparative Case Series.

OBJECTIVE: The objective of this study was to report medium-term outcomes of a novel combination of phacoemulsification with transscleral cyclophotocoagulation (phaco-TCP) compared with combined phacoemulsification and endoscopic cyclophotocoagulation (phaco-ECP) in patients with uncontrolled or suboptimally controlled glaucoma and coexisting cataract. MATERIALS AND METHODS: Retrospective case series of 80 consecutive patients with a minimum of 12 months of follow-up. In total, 46 eyes underwent phaco-ECP and 34 phaco-TCP. Success was defined as intraocular pressure (IOP) between 6 and 21 mm Hg with ≥20% reduction from preoperative IOP (with no increase in ocular hypotensive medications or further glaucoma surgery). Secondary outcomes were change in IOP, number of ocular hypotensive medications and safety. RESULTS: The mean follow-up was 32.6 ±10.3 months. Preoperative clinical characteristics were similar in both groups. At latest follow-up, success rate was greater with phaco-TCP than phaco-ECP (67.6% and 47.8%, P=0.037). IOP was also significantly lower after phaco-TCP (14.88±5.57 mm Hg, from 22.62±6.52 mm Hg) than phaco-ECP (18.07±6.72 mm Hg, from 22.83±7.88, P=0.0273). Ocular hypotensive medications required reduced similarly after phaco-TCP (from 3.38±0.88 to 2.65±1.04 medications, P=0.0012) and phaco-ECP (from 3.07±0.929 to 2.63±1.42 medications, P=0.0108). There were no cases of hypotony or reduction in vision related to glaucoma with either surgical intervention and a similar proportion required further glaucoma surgery (phaco-ECP 15.2%, phako-TCP 5.9%, P=0.2884). CONCLUSIONS: Phaco-TCP appears more successful in controlling IOP than phaco-ECP with similar safety. Further investigation is warranted of this newly proposed combination which may be particularly useful where access or experience with ECP or other minimally invasive glaucoma surgery is limited.

Optic Nerve Sheath Fenestration With a Multi-Arm Continuum Robot.

This article presents a medical robotic system for deep orbital interventions, with a focus on Optic Nerve Sheath Fenestration (ONSF). ONSF is a currently invasive ophthalmic surgical approach that can reduce potentially blinding elevated hydrostatic intracranial pressure on the optic disc via an incision on the optic nerve. The prototype is a multi-arm system capable of dexterous manipulation and visualization of the optic nerve area, allowing for a minimally invasive approach. Each arm is an independently controlled concentric tube robot collimated by a bespoke guide that is secured on the eye sclera via sutures. In this article, we consider the robot's end-effector design in order to reach/navigate the optic nerve according to the clinical requirements of ONSF. A prototype of the robot was engineered, and its ability to penetrate the optic nerve was analysed by conducting ex vivo experiments on porcine optic nerves and comparing their stiffness to human ones. The robot was successfully deployed in a custom-made realistic eye phantom. Our simulation studies and experimental results demonstrate that the robot can successfully navigate to the operation site and carry out the intervention.

Learned optical flow for intra-operative tracking of the retinal fundus.

PURPOSE: Sustained delivery of regenerative retinal therapies by robotic systems requires intra-operative tracking of the retinal fundus. We propose a supervised deep convolutional neural network to densely predict semantic segmentation and optical flow of the retina as mutually supportive tasks, implicitly inpainting retinal flow information missing due to occlusion by surgical tools. METHODS: As manual annotation of optical flow is infeasible, we propose a flexible algorithm for generation of large synthetic training datasets on the basis of given intra-operative retinal images. We evaluate optical flow estimation by tracking a grid and sparsely annotated ground truth points on a benchmark of challenging real intra-operative clips obtained from an extensive internally acquired dataset encompassing representative vitreoretinal surgical cases. RESULTS: The U-Net-based network trained on the synthetic dataset is shown to generalise well to the benchmark of real surgical videos. When used to track retinal points of interest, our flow estimation outperforms variational baseline methods on clips containing tool motions which occlude the points of interest, as is routinely observed in intra-operatively recorded surgery videos. CONCLUSIONS: The results indicate that complex synthetic training datasets can be used to specifically guide optical flow estimation. Our proposed algorithm therefore lays the foundation for a robust system which can assist with intra-operative tracking of moving surgical targets even when occluded.

Deep iterative vessel segmentation in OCT angiography.

This paper addresses retinal vessel segmentation on optical coherence tomography angiography (OCT-A) images of the human retina. Our approach is motivated by the need for high precision image-guided delivery of regenerative therapies in vitreo-retinal surgery. OCT-A visualizes macular vasculature, the main landmark of the surgically targeted area, at a level of detail and spatial extent unattainable by other imaging modalities. Thus, automatic extraction of detailed vessel maps can ultimately inform surgical planning. We address the task of delineation of the Superficial Vascular Plexus in 2D Maximum Intensity Projections (MIP) of OCT-A using convolutional neural networks that iteratively refine the quality of the produced vessel segmentations. We demonstrate that the proposed approach compares favourably to alternative network baselines and graph-based methodologies through extensive experimental analysis, using data collected from 50 subjects, including both individuals that underwent surgery for structural macular abnormalities and healthy subjects. Additionally, we demonstrate generalization to 3D segmentation and narrower field-of-view OCT-A. In the future, the extracted vessel maps will be leveraged for surgical planning and semi-automated intraoperative navigation in vitreo-retinal surgery.

Detailed Phenotyping and Therapeutic Strategies for Intronic ABCA4 Variants in Stargardt Disease.

Stargardt disease is a progressive retinal disorder caused by bi-allelic mutations in the ABCA4 gene that encodes the ATP-binding cassette, subfamily A, member 4 transporter protein. Over the past few years, we and others have identified several pathogenic variants that reside within the introns of ABCA4, including a recurrent variant in intron 36 (c.5196+1137G>A) of which the pathogenicity so far remained controversial. Detailed clinical characterization of this variant confirmed its pathogenic nature, and classified it as an allele of intermediate severity. Moreover, we discovered several additional ABCA4 variants clustering in intron 36. Several of these variants resulted in aberrant splicing of ABCA4, i.e., the inclusion of pseudoexons, while the splicing defects caused by the recurrent c.5196+1137G>A variant strongly increased upon differentiation of patient-derived induced pluripotent stem cells into retina-like cells. Finally, all splicing defects could be rescued by the administration of antisense oligonucleotides that were designed to specifically block the pseudoexon insertion, including rescue in 3D retinal organoids harboring the c.5196+1137G>A variant. Our data illustrate the importance of intronic variants in ABCA4 and expand the therapeutic possibilities for overcoming splicing defects in Stargardt disease.

Advances in retinal prosthesis systems.

Retinal prosthesis systems have undergone significant advances in the past quarter century, resulting in the development of several different novel surgical and engineering approaches. Encouraging results have demonstrated partial visual restoration, with improvement in both coarse objective function and performance of everyday tasks. To date, four systems have received marketing approval for use in Europe or the United States, with numerous others undergoing preclinical and clinical evaluation, reflecting the established safety profile of these devices for chronic implantation. This progress represents the first notion that the field of visual restorative medicine could offer blind patients a hope of real and measurable benefit. However, there are numerous complex engineering and biophysical obstacles still to be overcome, to reconcile the gap that remains between artificial and natural vision. Current developments in the form of enhanced image processing algorithms and data transfer approaches, combined with emerging nanofabrication and conductive polymerization techniques, herald an exciting and innovative future for retinal prosthetics. This review provides an update of retinal prosthetic systems currently undergoing development and clinical trials while also addressing future challenges in the field, such as the assessment of functional outcomes in ultra-low vision and strategies for tackling existing hardware and software constraints.

Optic Disc Pit Maculopathy: New Perspectives on the Natural History.

PURPOSE: To investigate the natural history of optic disc pit maculopathy and explore the associations between demographic, anatomic, and functional characteristics. DESIGN: Retrospective, comparative case series. METHODS: This was a single-center medical record review of previously untreated optic disc pit maculopathy. Baseline data of visual function, demographics, and pit physiognomy were collected, and further subgroup analysis was undertaken on patients with long-term follow-up, according to whether they were monitored or received surgical intervention. LogMAR visual acuity was the primary outcome measure, and anatomic characteristics were reported where available. RESULTS: Eighty-seven patients were identified with a new presentation of optic disc pit maculopathy. No demographic or pit features were correlated with vision at baseline. In 51 patients with available optical coherence tomography data, only the presence of subretinal fluid at baseline was associated with poorer visual acuity (P < .001). Fifty-two patients who were monitored without treatment had available long-term follow-up data. The mean change in visual acuity in this group was 0.01, with 77% maintaining visual acuity ≤0.30. Twenty-seven patients underwent surgery and showed significant postoperative improvement in vision (P < .001), with 59% achieving an acuity ≤0.30. Duration of postoperative follow-up was associated with better visual acuity (P = .007). CONCLUSION: Many patients with optic disc pit maculopathy maintain good long-term visual acuity and may demonstrate resolution of subretinal fluid in the absence of surgical intervention. There may be evidence to support delaying surgical treatment until visual deterioration is observed because of the potential stability or spontaneous improvement of the condition, the high rate of reoperation, and the long-term positive outcomes of deferred intervention.

Orbital plasmablastic lymphoma.

Plasmablastic lymphoma is an unusual and aggressive form of diffuse large B-cell lymphoma, which arises more commonly within the oronasal mucosa. It should be considered as a differential diagnosis for rapidly growing periorbital lesions, particularly in the context of HIV positivity.

An unusual case of bilateral pigmented maculopathy and anterior segment dysgenesis.

PURPOSE: Pigmentary maculopathy can occur in the context of various inherited and acquired diseases. Anterior segment dysgenesis arises due to developmental anomalies and may be associated with systemic disease, as in Rieger syndrome. CASE REPORT: A 49-year-old woman presented with longstanding reduction in vision, evidence of anterior segment dysgenesis, and multiple discrete pigmented lesions throughout the macula bilaterally. Electroretinographic findings were consistent with severe macular dysfunction. Gene array analysis did not reveal any chromosomal imbalances or other specific abnormalities. CONCLUSIONS: This is a unique case of bilateral pigmentary maculopathy and anterior segment dysgenesis, with clinical findings that are not characteristic of previously reported disease.

Phacoemulsification plus endoscopic cyclophotocoagulation versus phacoemulsification alone in primary open-angle glaucoma.

PURPOSE: To examine the efficacy and safety of combined phacoemulsification and endoscopic cyclophotocoagulation (phaco-ECP) compared to phacoemulsification alone in patients with primary open-angle glaucoma (POAG). METHODS: We performed a retrospective notes review of 99 consecutive clinical records of patients with POAG from 2 London eye departments. A total of 69 patients who underwent phaco-ECP and 30 sex- and age-matched control patients who underwent cataract surgery alone were included. Data on intraocular pressure (IOP), visual acuity (VA), number of ocular hypotensive medications, and postoperative complications were collected over 12 months. The primary outcome measure was defined as an IOP within normal limits (<21 mm Hg) and at least a 20% reduction in IOP from baseline. RESULTS: Mean IOP was significantly decreased in both groups after 1 year (p<0.001 from baseline). The success rate was significantly higher in the phaco-ECP group (69.6%) than in the phaco group (40%) after 1 year (p = 0.004). Reduction in mean IOP and number of medications was also greater in the phaco-ECP group after 1 year (IOP reduction: 4.5 ± 5.13 mm Hg vs 1.83 ± 3.61 mm Hg; p = 0.007; number of medications reduction: 0.73 ± 0.71 vs 0.23 ± 0.56; p = 0.001). Both groups achieved a similar improvement in VA. There was a higher incidence of minor and self-limiting complications in the phaco-ECP group (p<0.047). CONCLUSIONS: Phaco-ECP resulted in a greater reduction in IOP and number of medications than phacoemulsification alone in POAG.

Genetic and Environmental Factors Associated With the Ganglion Cell Complex in a Healthy Aging British Cohort.

IMPORTANCE: Measurement of ganglion cell complex (GCC) thickness may be more sensitive than current methods for glaucoma diagnosis and research. However, little is known about the factors influencing GCC thickness in the general population. OBJECTIVES: To investigate the heritability of and factors associated with GCC thickness in a healthy aging population. DESIGN, SETTING, AND PARTICIPANTS: A cross-sectional twin study was conducted from August 27, 2014, to March 31, 2016, among 1657 participants of white British ancestry from the TwinsUK study cohort without ocular pathologic conditions. Heritability analyses were conducted in 1432 twins (426 monozygous and 290 dizygous pairs). Association analyses were performed using univariable and multivariable stepwise linear regression models, taking family structure into account. Heritability analyses were conducted using maximum likelihood structural equation twin modeling. MAIN OUTCOMES AND MEASURES: Parameters measured included GCC thickness, autorefraction, intraocular pressure, blood pressure, body mass index, and cholesterol, creatinine, glucose, insulin, triglycerides, and urea levels. Estimated glomerular filtration rate was calculated using the Modification of Diet in Renal Disease formula. RESULTS: Among the 1657 participants (mean [SD] age, 56.0 [15.3] years; 89.5% women and 10.5% men), the mean [SD] inner GCC thickness was 96.0 [7.6] µm (95% CI, 95.1-96.2). In multivariable modeling, the mean inner GCC thickness was associated with advancing age (ß, -0.14; P < .001), increased body mass index (ß, -0.15; P = .001), spherical equivalent (ß, 0.70; P < .001), and higher estimated glomerular filtration rate (ß, 0.03; P = .02). A 1-U increase in age or body mass index was associated with a 0.14-µm and 0.15-µm decrease in GCC thickness, respectively (P < .001), while a 1-U increase in spherical equivalent or estimated glomerular filtration rate was associated with a 0.70-µm (P < .001) and 0.03-µm (P = .02) increase in GCC thickness, respectively. Ganglion cell complex thickness was not associated with sex, intraocular pressure, or diabetes. Age-adjusted GCC thickness was highly heritable, with additive genetic effects explaining 81% (95% CI, 78%-84%) of phenotypic variance and individual environmental factors explaining the remaining 19% (95% CI, 16%-22%). CONCLUSIONS AND RELEVANCE: Ganglion cell complex thickness appears to be highly heritable and further genetic analysis may help identify new biological pathways for glaucoma. The results suggest it may be important to account for age, body mass index, refractive error, and sex when using GCC thickness as a diagnostic tool. Replication of their results is required, as is further research to explain the association between renal function and GCC thickness.