Glaucoma

Glaucoma Publications

Huang AS, Hirabayashi K, Barna L, Parikh D, Pasquale LR. Assessment of a Large Language Model's Responses to Questions and Cases About Glaucoma and Retina Management. JAMA Ophthalmol 2024;Abstract
IMPORTANCE: Large language models (LLMs) are revolutionizing medical diagnosis and treatment, offering unprecedented accuracy and ease surpassing conventional search engines. Their integration into medical assistance programs will become pivotal for ophthalmologists as an adjunct for practicing evidence-based medicine. Therefore, the diagnostic and treatment accuracy of LLM-generated responses compared with fellowship-trained ophthalmologists can help assess their accuracy and validate their potential utility in ophthalmic subspecialties. OBJECTIVE: To compare the diagnostic accuracy and comprehensiveness of responses from an LLM chatbot with those of fellowship-trained glaucoma and retina specialists on ophthalmological questions and real patient case management. DESIGN, SETTING, AND PARTICIPANTS: This comparative cross-sectional study recruited 15 participants aged 31 to 67 years, including 12 attending physicians and 3 senior trainees, from eye clinics affiliated with the Department of Ophthalmology at Icahn School of Medicine at Mount Sinai, New York, New York. Glaucoma and retina questions (10 of each type) were randomly selected from the American Academy of Ophthalmology's Commonly Asked Questions. Deidentified glaucoma and retinal cases (10 of each type) were randomly selected from ophthalmology patients seen at Icahn School of Medicine at Mount Sinai-affiliated clinics. The LLM used was GPT-4 (version dated May 12, 2023). Data were collected from June to August 2023. MAIN OUTCOMES AND MEASURES: Responses were assessed via a Likert scale for medical accuracy and completeness. Statistical analysis involved the Mann-Whitney U test and the Kruskal-Wallis test, followed by pairwise comparison. RESULTS: The combined question-case mean rank for accuracy was 506.2 for the LLM chatbot and 403.4 for glaucoma specialists (n = 831; Mann-Whitney U = 27976.5; P < .001), and the mean rank for completeness was 528.3 and 398.7, respectively (n = 828; Mann-Whitney U = 25218.5; P < .001). The mean rank for accuracy was 235.3 for the LLM chatbot and 216.1 for retina specialists (n = 440; Mann-Whitney U = 15518.0; P = .17), and the mean rank for completeness was 258.3 and 208.7, respectively (n = 439; Mann-Whitney U = 13123.5; P = .005). The Dunn test revealed a significant difference between all pairwise comparisons, except specialist vs trainee in rating chatbot completeness. The overall pairwise comparisons showed that both trainees and specialists rated the chatbot's accuracy and completeness more favorably than those of their specialist counterparts, with specialists noting a significant difference in the chatbot's accuracy (z = 3.23; P = .007) and completeness (z = 5.86; P < .001). CONCLUSIONS AND RELEVANCE: This study accentuates the comparative proficiency of LLM chatbots in diagnostic accuracy and completeness compared with fellowship-trained ophthalmologists in various clinical scenarios. The LLM chatbot outperformed glaucoma specialists and matched retina specialists in diagnostic and treatment accuracy, substantiating its role as a promising diagnostic adjunct in ophthalmology.
Singh RK, Smith S, Fingert J, Gordon M, Kass M, Scheetz T, Segrè AV, Wiggs J, Elze T, Zebardast N. Machine Learning-Derived Baseline Visual Field Patterns Predict Future Glaucoma Onset in the Ocular Hypertension Treatment Study. Invest Ophthalmol Vis Sci 2024;65(2):35.Abstract
PURPOSE: The Ocular Hypertension Treatment Study (OHTS) identified risk factors for primary open-angle glaucoma (POAG) in patients with ocular hypertension, including pattern standard deviation (PSD). Archetypal analysis, an unsupervised machine learning method, may offer a more interpretable approach to risk stratification by identifying patterns in baseline visual fields (VFs). METHODS: There were 3272 eyes available in the OHTS. Archetypal analysis was applied using 24-2 baseline VFs, and model selection was performed with cross-validation. Decomposition coefficients for archetypes (ATs) were calculated. A penalized Cox proportional hazards model was implemented to select discriminative ATs. The AT model was compared to the OHTS model. Associations were identified between ATs with both POAG onset and VF progression, defined by mean deviation change per year. RESULTS: We selected 8494 baseline VFs. Optimal AT count was 19. The highest prevalence ATs were AT9, AT11, and AT7. The AT-based prediction model had a C-index of 0.75 for POAG onset. Multivariable models demonstrated that a one-interquartile range increase in the AT5 (hazard ratio [HR] = 1.14; 95% confidence interval [CI], 1.04-1.25), AT8 (HR = 1.22; 95% CI, 1.09-1.37), AT15 (HR = 1.26; 95% CI, 1.12-1.41), and AT17 (HR = 1.17; 95% CI, 1.03-1.31) coefficients conferred increased risk of POAG onset. AT5, AT10, and AT14 were significantly associated with rapid VF progression. In a subgroup analysis by high-risk ATs (>95th percentile or <75th percentile coefficients), PSD lost significance as a predictor of POAG in the low-risk group. CONCLUSIONS: Baseline VFs, prior to detectable glaucomatous damage, contain occult patterns representing early changes that may increase the risk of POAG onset and VF progression in patients with ocular hypertension. The relationship between PSD and POAG is modified by the presence of high-risk patterns at baseline. An AT-based prediction model for POAG may provide more interpretable glaucoma-specific information in a clinical setting.
Hoppe C, Gregory-Ksander M. The Role of Complement Dysregulation in Glaucoma. Int J Mol Sci 2024;25(4)Abstract
Glaucoma is a progressive neurodegenerative disease characterized by damage to the optic nerve that results in irreversible vision loss. While the exact pathology of glaucoma is not well understood, emerging evidence suggests that dysregulation of the complement system, a key component of innate immunity, plays a crucial role. In glaucoma, dysregulation of the complement cascade and impaired regulation of complement factors contribute to chronic inflammation and neurodegeneration. Complement components such as C1Q, C3, and the membrane attack complex have been implicated in glaucomatous neuroinflammation and retinal ganglion cell death. This review will provide a summary of human and experimental studies that document the dysregulation of the complement system observed in glaucoma patients and animal models of glaucoma driving chronic inflammation and neurodegeneration. Understanding how complement-mediated damage contributes to glaucoma will provide opportunities for new therapies.
Elwehidy AS, Toma J, Abd Elfattah D, Elhusseiny AM. The Use of Ologen Implant in Childhood Glaucoma Surgeries: A Review. Curr Eye Res 2024;:1-7.Abstract
PURPOSE: This study assesses the effectiveness and safety of using Ologen implants (Aeon Astron Europe BV, Leiden, The Netherlands) as an adjunctive therapy in childhood glaucoma surgeries. METHODS: We systematically reviewed the existing literature across various electronic databases to examine the effectiveness and safety of Ologen implants in childhood glaucoma surgeries. RESULTS: Our analysis encompassed 14 studies on the use of Ologen implants in childhood glaucoma. Among these, seven were prospective, five were retrospective, and two did not specify their study design. Success rates varied depending on the type of surgery and the included childhood glaucoma subtype. The success rates for Ologen implants-augmented surgeries were as follows: 33.3-70% for trabeculectomy, 50-81% for combined trabeculotomy-trabeculectomy procedure, 33%-87% for glaucoma drainage device, and 60% in deep sclerectomy. CONCLUSION: Ologen implant has a potential role in mitigating postoperative fibrosis and enhancing success rates in various childhood glaucoma surgeries. However, the existing literature is limited. Future comparative prospective studies with larger cohorts are needed.
WuDunn D, Takusagawa HL, Rosdahl JA, Sit AJ, Chopra V, Ou Y, Richter GM, Knight O'RJ, Solá-Del Valle D, Kim SJ. Central Visual Field Testing in Early Glaucoma: A Report by the American Academy of Ophthalmology. Ophthalmology 2024;131(2):240-248.Abstract
PURPOSE: To evaluate the current published literature on the utility of the 10-2 visual field (VF) testing strategy for the evaluation and management of early glaucoma, defined here as mean deviation (MD) better than -6 decibels (dB). METHODS: A search of the peer-reviewed literature was last conducted in June 2023 in the PubMed database. Abstracts of 986 articles were examined to exclude reviews and non-English-language articles. After inclusion and exclusion criteria were applied, 26 articles were selected, and the panel methodologist rated them for strength of evidence. Thirteen articles were rated level I, and 8 articles were rated level II. The 5 level III articles were excluded. Data from the 21 included articles were abstracted and reviewed. RESULTS: The central 12 locations on the 24-2 VF test grid lie within the central 10 degrees covered by the 10-2 VF test. In early glaucoma, defects detected within the central 10 degrees generally agree between the 2 tests. Defects within the central 10 degrees of the 24-2 VF test can predict defects on the 10-2 VF test, although the 24-2 may miss defects detected on the 10-2 VF test. In addition, results from the 10-2 VF test show better association with findings from OCT scans of the macular ganglion cell complex. Modifications of the 24-2 test that include extra test locations within the central 10 degrees improve detection of central defects found on 10-2 VF testing. CONCLUSIONS: Evidence to date does not support routine testing using 10-2 VF for patients with early glaucoma. However, early 10-2 VF testing may provide sufficient additional information for some patients, particularly those with a repeatable defect within the central 12 locations of the standard 24-2 VF test or who have inner retinal layer thinning on OCT scans of the macula. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.
Soh ZD, Tan M, Nongpiur ME, Xu BY, Friedman D, Zhang X, Leung C, Liu Y, Koh V, Aung T, Cheng C-Y. Assessment of angle closure disease in the age of artificial intelligence: A review. Prog Retin Eye Res 2024;98:101227.Abstract
Primary angle closure glaucoma is a visually debilitating disease that is under-detected worldwide. Many of the challenges in managing primary angle closure disease (PACD) are related to the lack of convenient and precise tools for clinic-based disease assessment and monitoring. Artificial intelligence (AI)- assisted tools to detect and assess PACD have proliferated in recent years with encouraging results. Machine learning (ML) algorithms that utilize clinical data have been developed to categorize angle closure eyes by disease mechanism. Other ML algorithms that utilize image data have demonstrated good performance in detecting angle closure. Nonetheless, deep learning (DL) algorithms trained directly on image data generally outperformed traditional ML algorithms in detecting PACD, were able to accurately differentiate between angle status (open, narrow, closed), and automated the measurement of quantitative parameters. However, more work is required to expand the capabilities of these AI algorithms and for deployment into real-world practice settings. This includes the need for real-world evaluation, establishing the use case for different algorithms, and evaluating the feasibility of deployment while considering other clinical, economic, social, and policy-related factors.
Liao C, Quigley H, Jiang Y, Huang S, Huang W, Friedman D, Foster PJ, He M. Iris volume change with physiologic mydriasis to identify development of angle closure: the Zhongshan Angle Closure Prevention Trial. Br J Ophthalmol 2024;108(3):366-371.Abstract
AIMS: To assess dynamic change of iris area (Iarea) and volume (VOL) with physiologic pupil dilation for progression of primary angle closure suspects. METHODS: Participants underwent baseline examinations including gonioscopy and anterior segment OCT (AS-OCT) as part of the Zhongshan Angle Closure Prevention Trial. The AS-OCT images were obtained both in the dark and light. Progression was defined as development of primary angle closure or an acute angle closure attack. Static ocular biometrics and dynamic changes were compared between progressors and non-progressors and multivariable logistic regression was developed to assess risk factors for progression. RESULTS: A mean 16.8% decrease in Iarea and a mean 6.26% decrease in VOL occurred with pupil dilation, while 22.96% non-progressors and 40% progressors presented VOL increases with pupil dilation. Iarea in light and dark and VOL in light were significantly smaller in progressors. In a multivariable logistic model, older age (p=0.008), narrower horizontal angle opening distance (AOD) 250 µm from the scleral spur (AOD250, p=0.001), flatter iris curvature (IC, p=0.006) and lower loss of iris volume (ΔVOL, p=0.04) were significantly associated with progression. With receiver operating characteristic analysis, the area under the curve for ΔVOL alone was 0.621, while that for the combined index (age, AOD250, IC and ΔVOL) was 0.824. Eyes with elevated intraocular pressure had less VOL loss compared with progressors developing peripheral anterior synechiae alone (p=0.055 for ΔVOL adjusted for pupil enlargement). CONCLUSION: A smaller change in ΔVOL is an additive risk factor to identify eyes more likely to develop angle closure disease. TRIAL REGISTRATION NUMBER: ISRCTN45213099.
Kavitha S, Tejaswini US, Venkatesh R, Zebardast N. Wound modulation in glaucoma surgery: The role of anti-scarring agents. Indian J Ophthalmol 2023;Abstract
Filtration surgery is one of the most frequently performed surgeries in the management of glaucoma, and trabeculectomy is considered the gold standard surgical technique for the same. Though trabeculectomy has been reported to have an excellent initial success rate, about 30% of them fail in 3 years, and nearly 50% of them fail in 5 years. The most significant risk of failure still seems to be wound scarring, especially episcleral fibrosis, leading to bleb failure. As a result, it is essential to explore the role of anti-scarring agents, including mitomycin C, and 5-fluorouracil in wound modulation and improving the bleb survival rate. Since these agents are widely used in trabeculectomy, it is crucial to understand the various modes of application, advantages, and adverse effects of these agents. On an evidence-based approach, all these points have been highlighted in this review article. In addition, the newer agents available for wound modulation and their scope for practical application are discussed.
Karg MM, Lu YR, Refaian N, Cameron J, Hoffmann E, Hoppe C, Shirahama S, Shah M, Krasniqi D, Krishnan A, Shrestha M, Guo Y, Cermak JM, Walthier M, Broniowska K, Rosenzweig-Lipson S, Gregory-Ksander M, Sinclair DA, Ksander BR. Sustained Vision Recovery by OSK Gene Therapy in a Mouse Model of Glaucoma. Cell Reprogram 2023;25(6):288-299.Abstract
Glaucoma, a chronic neurodegenerative disease, is a leading cause of age-related blindness worldwide and characterized by the progressive loss of retinal ganglion cells (RGCs) and their axons. Previously, we developed a novel epigenetic rejuvenation therapy, based on the expression of the three transcription factors Oct4, Sox2, and Klf4 (OSK), which safely rejuvenates RGCs without altering cell identity in glaucomatous and old mice after 1 month of treatment. In the current year-long study, mice with continuous or cyclic OSK expression induced after glaucoma-induced vision damage had occurred were tracked for efficacy, duration, and safety. Surprisingly, only 2 months of OSK fully restored impaired vision, with a restoration of vision for 11 months with prolonged expression. In RGCs, transcription from the doxycycline (DOX)-inducible Tet-On AAV system, returned to baseline 4 weeks after DOX withdrawal. Significant vision improvements remained for 1 month post switching off OSK, after which the vision benefit gradually diminished but remained better than baseline. Notably, no adverse effects on retinal structure or body weight were observed in glaucomatous mice with OSK continuously expressed for 21 months providing compelling evidence of efficacy and safety. This work highlights the tremendous therapeutic potential of rejuvenating gene therapies using OSK, not only for glaucoma but also for other ocular and systemic injuries and age-related diseases.
Goddin T-L, Yu H, Friedman DS, Owsley C, Kwon MY. MNREAD Reading Vision in Adults With Glaucoma Under Mesopic and Photopic Conditions. Invest Ophthalmol Vis Sci 2023;64(15):43.Abstract
PURPOSE: Despite good photopic visual acuity, glaucoma patients report difficulty performing daily activities under dim light such as reading. Here we investigated the impact of mesopic lighting conditions on reading vision of glaucoma patients. METHODS: The study design included 39 patients with glaucoma and 40 healthy controls. Reading vision was assessed with MNREAD charts under mesopic (2 cd/m2) and photopic (220 cd/m2) conditions. Four reading indexes: maximum reading speed (MRS), critical print size (CPS), reading acuity (RA), and reading accessibility index (ACC) were obtained from the MNREAD test yielding a plot of reading speed versus print size. RESULTS: Compared to photopic conditions, reading vision of both healthy controls and glaucoma patients significantly decreased under mesopic conditions (P < 0.05). For glaucoma patients (85% with mild or moderate glaucoma), MRS and ACC decreased by six words per minute and 0.1, respectively under mesopic conditions; CPS and RA increased by 0.25 and 0.18 logMAR, respectively. Moreover, under both photopic and mesopic conditions, reading vision of glaucoma patients was significantly worse than that of healthy controls, but the difference was greater under mesopic conditions (P < 0.05) even after controlling for age and visual acuity. CONCLUSIONS: Mesopic conditions make reading more challenging for both healthy controls and glaucoma patients. However, reading in dim light appears to be more burdensome for glaucoma patients. Mesopic reading tests mediated by both cone and rod photoreceptor systems likely provide a more sensitive and comprehensive assessment of a patient's reading impairment than testing under photopic conditions.
Gharahkhani P, He W, Han X, Ong JS, Rentería ME, Wiggs JL, Khawaja AP, Trzaskowski M, Mackey DA, Craig JE, Hewitt AW, Hewitt AW, Macgregor S, Wu Y. Genome-wide risk prediction of primary open-angle glaucoma across multiple ancestries. medRxiv 2023;Abstract
BACKGROUND: Primary open-angle glaucoma (POAG) is a leading cause of blindness worldwide. The disease is often only diagnosed after retinal ganglion cell damage has occurred, with current treatments unable to restore lost vision. Developing risk identification tools for POAG will help enable timely diagnosis and prevent irreparable damage from occurring, especially for ancestry groups (such as African (AFR)) where the disease prevalence is high. Given the heritable nature of POAG, we aim to develop a polygenic score (PGS), which could facilitate earlier POAG risk detection for timely prevention and diagnosis. METHODS: We applied a multi-ancestry multi-trait approach to build powerful PGS for POAG. We first integrated the new and existing genetics data on POAG and two key endophenotypes, intraocular pressure (IOP) and vertical cup-to-disc ratio (VCDR). We then leveraged the shared POAG genetic information across European (EUR), AFR and Asian ancestries and between POAG and each of IOP and VCDR to develop PGS for POAG risk prediction. We systematically assessed the PGS prediction power and risk stratification ability in POAG cohorts of different ancestries. RESULTS: Our newly developed PGS showed improved accuracy compared to previous PGS for POAG risk prediction in EUR ancestry. We showed the transferability of PGS based on EUR ancestry in the prediction of POAG status in AFR and Asian ancestries. Utilizing the shared genetic information across ancestries further improved PGS prediction power for POAG in AFR and East Asian (EAS). For individuals with South Asian ancestry, those in the top PGS decile were diagnosed ~18 years earlier than those in the bottom decile. For AFR ancestry, individuals in the top percentile had an odds ratio of 4.08 (95% CI: 2.33-7.45) compared with the remainder of the population using the newly developed AFR-specific PGS. CONCLUSIONS: In the current study, we developed PGS for POAG risk prediction in EUR, Asian and AFR populations. These PGS, to our best knowledge, are the most powerful PGS currently for POAG risk screening and stratification. We believe that our study will lead to improved POAG detection across diverse populations in the future by enabling targeting clinical screening of people at high levels of genetic risk.
Shi M, Sun JA, Lokhande A, Tian Y, Luo Y, Elze T, Shen LQ, Wang M. Artifact Correction in Retinal Nerve Fiber Layer Thickness Maps Using Deep Learning and Its Clinical Utility in Glaucoma. Transl Vis Sci Technol 2023;12(11):12.Abstract
PURPOSE: Correcting retinal nerve fiber layer thickness (RNFLT) artifacts in glaucoma with deep learning and evaluate its clinical usefulness. METHODS: We included 24,257 patients with optical coherence tomography and reliable visual field (VF) measurements within 30 days and 3,233 patients with reliable VF series of at least five measurements over ≥4 years. The artifacts are defined as RNFLT less than the known floor value of 50 µm. We selected 27,319 high-quality RNFLT maps with an artifact ratio (AR) of <2% as the ground truth. We created pseudo-artifacts from 21,722 low-quality RNFLT maps with AR of >5% and superimposed them on high-quality RNFLT maps to predict the artifact-free ground truth. We evaluated the impact of artifact correction on the structure-function relationship and progression forecasting. RESULTS: The mean absolute error and Pearson correlation of the artifact correction were 9.89 µm and 0.90 (P < 0.001), respectively. Artifact correction improved R2 for VF prediction in RNFLT maps with AR of >10% and AR of >20% up to 0.03 and 0.04 (P < 0.001), respectively. Artifact correction improved (P < 0.05) the AUC for progression prediction in RNFLT maps with AR of ≤10%, >10%, and >20%: (1) total deviation pointwise progression: 0.68 to 0.69, 0.62 to 0.63, and 0.62 to 0.64; and (2) mean deviation fast progression: 0.67 to 0.68, 0.54 to 0.60, and 0.45 to 0.56. CONCLUSIONS: Artifact correction for RNFLTs improves VF and progression prediction in glaucoma. TRANSLATIONAL RELEVANCE: Our model improves clinical usability of RNFLT maps with artifacts.
Lu ES, Cui Y, Le R, Zhu Y, Wang JC, Laíns I, Katz R, Lu Y, Zeng R, Garg I, Wu DM, Husain D, Kim LA, Miller JB. Widefield swept-source optical coherence tomography angiography metrics associated with neovascular glaucoma in patients with proliferative diabetic retinopathy. Graefes Arch Clin Exp Ophthalmol 2023;Abstract
PURPOSE: To explore the association between widefield swept-source optical coherence tomography angiography (WF SS-OCTA) metrics, including nonperfusion area (NPA) and neovascularization (NV), and presence of neovascular glaucoma (NVG) in patients with proliferative diabetic retinopathy (PDR). METHODS: A prospective, cross-sectional study was conducted from November 2018 to February 2020. A total of 85 eyes of 60 PDR patients without NVG and 9 eyes of 8 PDR patients with NVG were included. Retinal ischemic parameters (NPA; ischemia index [NPA/total retinal area]) and NV features (NV number; NV area; NV vessel density) were evaluated. Foveal avascular zone (FAZ), macular thickness/volume, and choroidal thickness/volume were obtained using the Zeiss ARI Network. WF SS-OCTA retinal and choroidal metrics, systemic, and ocular parameters were screened using Least Absolute Shrinkage and Selection Operator (LASSO) logistic regression for variable selection. Firth's bias-reduced logistic regression (outcome: presence of NVG) was subsequently used to identify parameters associated with NVG. RESULTS: After LASSO variable selection, 8 variables were significantly associated with the presence of NVG: DM duration (years), insulin (yes/no), best-corrected visual acuity (BCVA) (logMAR), IOP, ischemia index, skeletonized vessel density, macular thickness (inner inferior, outer temporal regions). Firth's bias-reduced logistic regression showed ischemia index (odds ratio [OR]=13.2, 95% confidence interval [CI]:5.3-30.7, P<0.001) and BCVA (OR=5.8, 95%CI:1.2-28.8, P<0.05) were associated with the presence of NVG. NV metrics, FAZ, and choroidal parameters were not related to NVG. CONCLUSIONS: Retinal ischemia but not NV was associated with the presence of NVG in patients with PDR using WF SS-OCTA. Larger, longitudinal studies are needed to validate imaging biomarkers associated with diabetic NVG.
Rajasundaram S, Zebardast N, Mehta P, Khawaja AP, Warwick A, Duchinski K, Burgess S, Gill D, Segrè AV, Wiggs J. TIE1 and TEK signalling, intraocular pressure, and primary open-angle glaucoma: a Mendelian randomization study. J Transl Med 2023;21(1):847.Abstract
BACKGROUND: In primary open-angle glaucoma (POAG), lowering intraocular pressure (IOP) is the only proven way of slowing vision loss. Schlemm's canal (SC) is a hybrid vascular and lymphatic vessel that mediates aqueous humour drainage from the anterior ocular chamber. Animal studies support the importance of SC endothelial angiopoietin-TEK signalling, and more recently TIE1 signalling, in maintaining normal IOP. However, human genetic support for a causal role of TIE1 and TEK signalling in lowering IOP is currently lacking. METHODS: GWAS summary statistics were obtained for plasma soluble TIE1 (sTIE1) protein levels (N = 35,559), soluble TEK (sTEK) protein levels (N = 35,559), IOP (N = 139,555) and POAG (Ncases = 16,677, Ncontrols = 199,580). Mendelian randomization (MR) was performed to estimate the association of genetically proxied TIE1 and TEK protein levels with IOP and POAG liability. Where significant MR estimates were obtained, genetic colocalization was performed to assess the probability of a shared causal variant (PPshared) versus distinct (PPdistinct) causal variants underlying TIE1/TEK signalling and the outcome. Publicly available single-nucleus RNA-sequencing data were leveraged to investigate differential expression of TIE1 and TEK in the human ocular anterior segment. RESULTS: Increased genetically proxied TIE1 signalling and TEK signalling associated with a reduction in IOP (- 0.21 mmHg per SD increase in sTIE1, 95% CI = - 0.09 to - 0.33 mmHg, P = 6.57 × 10-4, and - 0.14 mmHg per SD decrease in sTEK, 95% CI = - 0.03 to - 0.25 mmHg, P = 0.011), but not with POAG liability. Colocalization analysis found that the probability of a shared causal variant was greater for TIE1 and IOP than for TEK and IOP (PPshared/(PPdistinct + PPshared) = 0.98 for TIE1 and 0.30 for TEK). In the anterior segment, TIE1 and TEK were preferentially expressed in SC, lymphatic, and vascular endothelium. CONCLUSIONS: This study provides novel human genetic support for a causal role of both TIE1 and TEK signalling in regulating IOP. Here, combined evidence from cis-MR and colocalization analyses provide stronger support for TIE1 than TEK as a potential IOP-lowering therapeutic target.
Sun JA, Yuan M, Johnson GE, Pasquale LR, Boland MV, Friedman DS, Elze T, Shen LQ, Wang M. Comparison of Structural and Functional Features in Primary Angle-Closure and Open-Angle Glaucomas. J Glaucoma 2023;Abstract
PRECIS: Using a large dataset, we showed structural and functional differences between primary angle closure glaucoma and primary open angle glaucoma. Primary angle closure glaucoma has relative structural preservation and worse functional loss inferiorly. PURPOSE: To identify structural and functional differences in primary angle-closure glaucoma (PACG) and primary open-angle glaucoma (POAG). PATIENTS AND METHODS: In this large cross-sectional study, differences in structural and functional damage were assessed among POAG and PACG patients with optical coherence tomography and reliable visual field testing. RESULTS: 283 PACG and 4,110 POAG patients were included. Despite similar mean deviation on visual fields (mean [standard deviation] -7.73 [7.92] vs. -7.53 [6.90] dB, P=0.72), PACG patients had thicker global retinal nerve fiber layer (RNFL), smaller cup volume, smaller cup-to-disc ratio, and larger rim area than POAG (77 [20] vs. 71 [14] µm, 0.32 [0.28] vs. 0.40 [0.29] mm3, 0.6 [0.2] vs. 0.7 [0.1], 1.07 [0.40] vs. 0.89 [0.30] mm2, P<0.001 for all), while POAG patients had more pronounced inferior RNFL thinning (82 [24] vs. 95 [35] µm, P<0.001). In a multivariable analysis, hyperopia (odds ratio (OR): 1.24, confidence interval (CI): 1.13-1.37), smaller cup-to-disc ratio (OR: 0.69, CI: 0.61-0.78), thicker inferior RNFL (OR: 1.15, CI: 1.06-1.26) and worse mean deviation (OR: 0.95, CI: 0.92-0.98) were associated with PACG. Functionally, POAG was associated with superior paracentral loss and PACG with inferior field loss. After adjusting for average RNFL thickness, PACG was associated with more diffuse loss than POAG (TD differences 1.26-3.2 dB). CONCLUSIONS: PACG patients had less structural damage than POAG patients despite similar degrees of functional loss. Regional differences in patterns of functional and structural loss between POAG and PACG may improve disease monitoring for these glaucoma subtypes.

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