Glaucoma

Glaucoma Publications

Rong SS, Lu SY, Matsushita K, Huang C, Leung CKS, Kawashima R, Usui S, Tam POS, Young AL, Tsujikawa M, Zhang M, Nishida K, Wiggs JL, Tham CC, Pang CP, Chen LJ. Association of the SIX6 locus with primary open angle glaucoma in southern Chinese and Japanese. Exp Eye Res 2019;180:129-136.Abstract
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 (P = 4.3 × 10, OR = 0.72, I = 0). Additionally, we replicated the association of one known SNP, rs33912345 (P = 0.0061, OR = 0.69, I = 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 (P = 0.017, OR = 0.70, I = 53%). All these three SNPs were significantly associated with POAG when the three cohorts were combined in meta-analysis (P<0.005). Furthermore, two haplotypes, C-C (P = 1.13 × 10, OR = 1.41, I = 0) and A-A (P = 0.045, OR = 0.68, I = 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.
Lin MM, Rageh A, Turalba AV, Lee H, Falkenstein IA, Hoguet AS, Ojha P, Rao VS, Ratanawongphaibul K, Rhee DJ, Shen LQ, Song BJ, Chen TC. Differential Efficacy of Combined Phacoemulsification and Endocyclophotocoagulation in Open-angle Glaucoma versus Angle Closure Glaucoma. J Glaucoma 2019;Abstract
PRéCIS:: This retrospective study found that combined phacoemulsification and endocyclophotocoagulation reduced intraocular pressure to a greater degree in angle closure glaucoma versus open-angle glaucoma and was effective for all stages of glaucoma. PURPOSE: Endocyclophotocoagulation (ECP, Endo Optiks, Little Silver, NJ, USA) laser treatment of the ciliary processes is believed to decrease intraocular pressure (IOP) by reducing aqueous production. Anecdotal experience in angle closure glaucoma suggests that it may also lower IOP by opening the drainage angle to promote aqueous outflow. This study sought to evaluate combined phacoemulsification and ECP (phaco/ECP) in eyes with different types and stages of glaucoma. PATIENTS AND METHODS: Retrospective chart review of eyes that underwent phaco/ECP between October 2010 and December 2016 at one institution. RESULTS: In 63 eyes of 63 patients with an average of 3.0±1.7 years of follow-up, the 22 eyes with chronic angle closure glaucoma (CACG) had greater IOP reduction and medication reduction than the 41 eyes with primary open angle glaucoma (POAG) at both 1 year (6.4 vs. 2.1▒mmHg, P=0.01; 0.9 vs. 0.2 medications, P=0.04) and final follow-up (6.2 vs. 2.4▒mmHg, P=0.02; 0.9 vs. 0.3 medications, P=0.05). There was no difference in IOP reduction or medication reduction for eyes with mild, moderate, or advanced glaucoma at both 1 year (3.5, 3.9, 0.5▒mmHg, respectively, P=0.18; 0.3, 0.6, 0.4 medications, P=0.58) and final follow-up (3.3, 4.8, 0.7▒mmHg, P=0.11; 0.1, 0.8, 0.4 medications, P=0.14). CONCLUSIONS: Eyes with CACG were more responsive to phaco/ECP in terms of IOP and medication reduction compared to eyes with POAG. This finding could be partially or entirely due to concurrent cataract extraction and greater CACG pre-operative IOP. Phaco/ECP was effective in all stages of glaucoma.This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. http://creativecommons.org/licenses/by-nc-nd/4.0/.
Marando CM, Mansouri K, Kahook MY, Seibold LK. Tolerability and Functionality of a Wireless 24-Hour Ocular Telemetry Sensor in African American Glaucoma Patients. J Glaucoma 2019;28(2):119-124.Abstract
PURPOSE: The purpose of the study was to evaluate the tolerability and functionality of a wireless ocular telemetry sensor in African American patients with glaucoma. MATERIALS AND METHODS: In this prospective, observational cohort study, 20 African American patients with primary open angle glaucoma (POAG) were evaluated at the University of Colorado Eye Center. Before lens placement, patients recorded ocular comfort and underwent a baseline eye exam. Following the exam, patients were fitted with a SENSIMED Triggerfish contact lens sensor and data recording device. Patients were sent home and instructed to record their activities in a journal and return in 24 hours. Repeat exams were performed at various time points in clinic before and after lens removal. RESULTS: All 20 patients retained the lens for the 24-hour study period. The patient reported comfort was excellent, with a nadir of mean recorded comfort of 7.05/10. Significant clinical changes were noted in lid/conjunctival erythema, BCVA, refraction, and pachymetry over the course of lens wear. The majority of these changes were improved or resolved by 1 hour after lens removal. Voltage output was significantly greater nocturnally than diurnally (184.79 mV and 71.48 mV, respectively; P<0.0001). There was no significant change in signal variability or slope over the entire duration of the sleep/wake period based on sleep. CONCLUSIONS: The wireless ocular sensor is well tolerated over a 24-hour period in African American patients with POAG despite transient changes in visual acuity and conjunctival erythema. Clinically usable 24-hour profiles were generated for all patients, with voltage output increasing significantly during periods of sleep.
Chan W, Wiggs JL, Sobrin L. The genetic influence on corticosteroid-induced ocular hypertension: A field positioned for discovery. Am J Ophthalmol 2019;Abstract
PURPOSE: To provide evidence that corticosteroid-induced ocular hypertension has a genetic component. DESIGN: Evidence-based Perspective. METHODS: We conducted a comprehensive literature search for studies exploring genetic influences on intraocular pressure responses to corticosteroid treatment. RESULTS: Studies demonstrating increased risk of corticosteroid-induced ocular hypertension among first-degree relatives of affected individuals support a genetic contribution to the disease. Family and personal history of primary open glaucoma also increases the risk of corticosteroid-induced intraocular pressure elevation suggesting common genetic etiologies. A number of studies have attempted to identify predisposing genetic factors, however reproducible findings have not yet been reported. The recent availability of large data sets with clinical and genetic data for patients affected by corticosteroid-induced ocular hypertension and glaucoma provides new opportunities to study the genetic underpinnings of this important condition. CONCLUSIONS: There is substantial evidence suggesting a genetic component to corticosteroid-related ocular hypertension and glaucoma, but specific genetic risk factors have yet to be identified. The current confluence of large genetic data sets and affordable genetic sequencing technologies has great potential for discovering the genes that increase risk for this blinding complication of corticosteroid therapy.
Saeedi OJ, Elze T, D'Acunto L, Swamy R, Hegde V, Gupta S, Venjara A, Tsai J, Myers JS, Wellik SR, De Moraes CG, Pasquale LR, Shen LQ, Boland MV. Agreement and Predictors of Discordance of Six Visual Field Progression Algorithms. Ophthalmology 2019;Abstract
PURPOSE: To determine the agreement of six established visual field progression algorithms in a large dataset of visual fields from multiple institutions and to determine predictors of discordance amongst these algorithms. DESIGN: Retrospective Longitudinal Cohort Subjects, Participants, and/or Controls: Visual fields from five major eye care institutions in the United States. This analysis included a subset of eyes with at least five SITA-Standard 24-2 visual fields that met our reliability criteria. Of a total of 831,240 fields, a subset of 90,713 visual fields of 13,156 eyes of 8,499 patients met the inclusion criteria. METHODS: Six commonly used visual field progression algorithms (mean deviation slope, visual field index slope, Advanced Glaucoma Intervention Study, Collaborative Initial Glaucoma Treatment Study, pointwise linear regression, and permutation of pointwise linear regression) were applied to this cohort and each eye was determined to be stable or progressing using each measure. Agreement between individual algorithms was tested using Cohen's Kappa coefficient. Bivariate and multivariable analyses were used to determine predictors of discordance (3 algorithms progressing and 3 algorithms stable). MAIN OUTCOME MEASURES: Agreement and discordance between algorithms RESULTS: Individual algorithms showed poor to moderate agreement with each other when compared directly (Kappa range: 0.12 - 0.52). 11.7% of eyes progressed based on at least four algorithms. Major predictors of discordance, or lack of agreement among algorithms were more depressed initial MD (P <0.01) and older age at first available visual field (P < 0.01). A greater number of visual fields (P<0.01), more years of follow up (P < 0.01) and eye care institution (P = 0.03) were also associated with discordance. CONCLUSIONS: This extremely large comparative series demonstrates that existing algorithms have limited agreement, and that agreement varies with clinical parameters including institution. These issues underscore the challenges to the clinical use and application of progression algorithms and of applying "big data" results to individual practices.
Wang M, Shen LQ, Pasquale LR, Petrakos P, Formica S, Boland MV, Wellik SR, De Moraes CG, Myers JS, Saeedi O, Wang H, Baniasadi N, Li D, Tichelaar J, Bex PJ, Elze T. An Artificial Intelligence Approach to Detect Visual Field Progression in Glaucoma Based on Spatial Pattern Analysis. Invest Ophthalmol Vis Sci 2019;60(1):365-375.Abstract
Purpose: To detect visual field (VF) progression by analyzing spatial pattern changes. Methods: We selected 12,217 eyes from 7360 patients with at least five reliable 24-2 VFs and 5 years of follow-up with an interval of at least 6 months. VFs were decomposed into 16 archetype patterns previously derived by artificial intelligence techniques. Linear regressions were applied to the 16 archetype weights of VF series over time. We defined progression as the decrease rate of the normal archetype or any increase rate of the 15 VF defect archetypes to be outside normal limits. The archetype method was compared with mean deviation (MD) slope, Advanced Glaucoma Intervention Study (AGIS) scoring, Collaborative Initial Glaucoma Treatment Study (CIGTS) scoring, and the permutation of pointwise linear regression (PoPLR), and was validated by a subset of VFs assessed by three glaucoma specialists. Results: In the method development cohort of 11,817 eyes, the archetype method agreed more with MD slope (kappa: 0.37) and PoPLR (0.33) than AGIS (0.12) and CIGTS (0.22). The most frequently progressed patterns included decreased normal pattern (63.7%), and increased nasal steps (16.4%), altitudinal loss (15.9%), superior-peripheral defect (12.1%), paracentral/central defects (10.5%), and near total loss (10.4%). In the clinical validation cohort of 397 eyes with 27.5% of confirmed progression, the agreement (kappa) and accuracy (mean of hit rate and correct rejection rate) of the archetype method (0.51 and 0.77) significantly (P < 0.001 for all) outperformed AGIS (0.06 and 0.52), CIGTS (0.24 and 0.59), MD slope (0.21 and 0.59), and PoPLR (0.26 and 0.60). Conclusions: The archetype method can inform clinicians of VF progression patterns.
Guo Z-Z, Chang K, Wei X. Intraocular pressure fluctuation and the risk of glaucomatous damage deterioration: a Meta-analysis. Int J Ophthalmol 2019;12(1):123-128.Abstract
AIM: To systematically review whether the increased fluctuation of intraocular pressure (IOP) is a risk factor for open angle glaucoma (OAG) progression. METHODS: Scientific studies relevant to IOP fluctuation and glaucoma progression were retrieved from MEDLINE, EMBASE and CENTRAL databases, and were listed as references in this paper. The hazard ratio (HR) was calculated by using fixed or random-effects models according to the heterogeneity of included studies. RESULTS: Individual data for 2211 eyes of 2637 OAG patients in fourteen prospective studies were included in this Meta-analysis. All studies were longitudinal clinical studies with follow-up period ranging from 3 to 8.5y. The combined HR was 1.23 (95%CI 1.04-1.46, =0.02) for the association between IOP fluctuation and glaucoma onset or progression with the evidence of heterogeneity (<0.1). Subgroup analyses with different types of IOP fluctuation were also evaluated. Results indicated that the summary HR was 0.98 (95%CI 0.78-1.24) in short-term IOP fluctuation group, which showed no statistical significance with heterogeneity, whereas, the combined HR was 1.43 (95%CI 1.13-1.82, =0.003) in long-term IOP fluctuation group without homogeneity. Sensitivity analysis further showed that the pooled HR was 1.10 (95%CI 1.03-1.18, =0.004) for long-term IOP fluctuation and visual function progression with homogeneity among studies (=0.3). CONCLUSION: Long-term IOP fluctuation can be a risk factor for glaucoma progression based on the presented evidence. Thus, controlling the swing of IOP is crucial for glaucoma or glaucoma suspecting patients.
Wei X, Cho K-S, Thee EF, Jager MJ, Chen DF. Neuroinflammation and microglia in glaucoma: time for a paradigm shift. J Neurosci Res 2019;97(1):70-76.Abstract
Glaucoma is a complex neurodegenerative disease with many clinical subtypes. Some of its rare forms include pigmentary glaucoma, uveitic glaucoma and congenital glaucoma. While they all share common features of progressive retinal ganglion cell (RGC) loss, optic nerve damage and corresponding visual field loss, the exact mechanisms underlying glaucomatous neuron loss are not clear. This has largely hindered the development of a real cure for this disease. Elevated intraocular pressure (IOP) is a known major risk factor of glaucoma; however, progressive degeneration of RGCs and axons can also be found in patients with a normal IOP, i.e., normal tension glaucoma (NTG). Interestingly, patients who carry the gain-of-function mutation of the pro-inflammatory gene TBK1 - tumor necrosis factor (TNF) receptor associated factor NF-κB activator (TANK) binding kinase 1 - are at increased risk to develop NTG. This finding suggests a causal link between neuroinflammatory processes and glaucoma. Various studies have reported the presence of neuroinflammatory responses by microglia, astrocytes and other blood-born immune cells in the optic nerve head (ONH) at early stages of experimental glaucoma. Inhibition of certain pro-inflammatory pathways, particularly those associated with microglial activation, appears to be neuroprotective. In this review, we will focus on the inflammatory responses, in particular the proposed roles of microglia, in the pathogenesis of glaucoma.
Cousins CC, Chou JC, Greenstein SH, Brauner SC, Shen LQ, Turalba AV, Houlihan P, Ritch R, Wiggs JL, Knepper PA, Pasquale LR. Resting nailfold capillary blood flow in primary open-angle glaucoma. Br J Ophthalmol 2019;103(2):203-207.Abstract
BACKGROUND/AIMS: An altered haemodynamic profile for various ocular posterior segment capillary beds has been documented in primary open-angle glaucoma (POAG). POAG may also involve abnormal non-ocular blood flow, and the nailfold capillaries, which are not affected by elevated intraocular pressure (IOP), are readily assessable. METHODS: We measured resting nailfold capillary blood flow in 67 POAG and 63 control subjects using video capillaroscopy. Masked readers tracked blood column voids between consecutive, registered image sequence frames, measured vessel diameter and calculated blood flow. We used multiple logistic regression to investigate the relation between nailfold capillary blood flow and POAG. In secondary analyses, we stratified cases by maximum IOP and concurrent topical beta-blocker use. RESULTS: Mean (±SD) blood flow in picolitres per second was 26.8±17.6 for POAG cases and 50.1±24.2 for controls (p<0.0001). After adjustment for demographic and clinical factors including blood pressure and pulse, every picolitre per second increase in resting nailfold blood flow was associated with a 6% (95% CI 0.92 to 0.96) reduced odds of POAG (p<0.0001). Similar relations between nailfold capillary blood flow and POAG were found for cases stratified by maximum known IOP and for cases stratified by concurrent topical beta-blocker use. CONCLUSION: Reduced resting nailfold capillary blood flow is present in POAG independent of covariates such as blood pressure, pulse and IOP.
Tiedemann D, Mouhammad ZA, Utheim TP, Dartt DA, Heegaard S, Petrovski G, Kolko M. Conjunctival Goblet Cells, the Overlooked Cells in Glaucoma Treatment. J Glaucoma 2018;Abstract
Glaucoma is the leading cause of irreversible blindness worldwide. Although no definitive cure exists, lowering of the intraocular pressure decreases the rate of progression in the majority of patients with glaucoma. Anti-glaucomatous treatment modalities consist predominantly of chronic use of eye drops. It has become increasingly evident that long-term exposure to eye drops has a significant impact on the ocular surface, and thereby on patient compliance and quality of life. Maintenance of the ocular surface is highly dependent on a stable tear film. Conjunctival goblet cells of the ocular surface play an important role in providing the innermost mucin layer of the tear film and are essential for maintaining the ocular surface homeostasis. Recent studies have reported severe side effects of anti-glaucomatous drops on goblet cells. In particular, a preservative containing anti-glaucomatous drops have been shown to affect the viability and functions of the goblet cells. Furthermore, goblet cell density has been suggested as a potential predictor of surgical outcome following filtration surgery. The present review provides an overview of the current literature on the impact of anti-glaucomatous eye drops on goblet cells as well as the impact on the ocular surface. Moreover, the existing evidence of a possible association between goblet cell density and glaucoma filtration surgery outcome is summarized. We conclude that prostaglandin analogues spare the conjunctival goblet cells more compared to other anti-glaucomatous drops and that goblet cells may be a good predictor of surgical outcome following filtration surgery. Overall, given the multiple functions of goblet cells in the ocular surface homeostasis, dedicated strategies should be adopted to preserve this cell population during the course of glaucoma.
Lee SSY, Yazar S, Pasquale LR, Sanfilippo PG, Hewitt AW, Hickey M, Skinner R, Mackey DA. The Relationship Between Optic Disc Parameters and Female Reproductive Factors in Young Women. Asia Pac J Ophthalmol (Phila) 2018;Abstract
PURPOSE: It has been suggested that female sex steroids have neuroprotective properties that may reduce risk of glaucoma in premenopausal women. In this study, we explored the associations of optic disc measures with female reproductive factors in a population of young women. DESIGN: Cohort study. METHODS: Young women (n = 494; age range, 18-22 years) were recruited as part of the Western Australian Pregnancy Cohort (Raine) Study. Information on age at menarche, parity, and use of hormonal contraceptives were obtained from questionnaires. Participants underwent an eye examination, including spectral-domain optical coherence tomography imaging, to obtain optic disc parameters. RESULTS: Women who had given birth at least once (parous women; n = 10) had larger vertical neuroretinal rim widths ( < 0.001) than nulliparous women (n = 484) after correcting for use of hormonal contraceptives, intraocular pressure, refractive error, and family history of glaucoma. Furthermore, vertical and horizontal cup-to-disc ratios, which are inherently related to neuroretinal rim width, were found to be smaller among parous women compared with nulliparous women (both < 0.001). Age at menarche and use of hormonal contraceptives were not significantly associated with any optic disc parameters. CONCLUSIONS: We found limited evidence that female reproductive factors were related with optic disc parameters during young adulthood. The association between parity and optic disc parameter, though significant, should be further investigated given the small number of parous women in the current sample. Future follow-ups of this cohort will allow us to explore for any associations of these factors with optic disc parameters and glaucoma risk at an older age.
Lahola-Chomiak AA, Footz T, Nguyen-Phuoc K, Neil GJ, Fan BJ, Allen KF, Greenfield DS, Parrish RK, Linkroum K, Pasquale LR, Leonhardt RM, Ritch R, Javadiyan S, Craig JE, Ted Allison W, Lehmann OJ, Walter MA, Wiggs JL. Non-Synonymous variants in Premelanosome Protein (PMEL) cause ocular pigment dispersion and pigmentary glaucoma. Hum Mol Genet 2018;Abstract
Pigmentary Glaucoma (PG) is a common glaucoma subtype that results from release of pigment from the iris, called Pigment Dispersion Syndrome (PDS), and its deposition throughout the anterior chamber of the eye. Although PG has a substantial heritable component, no causative genes have yet been identified. We used Whole Exome Sequencing (WES) of two independent pedigrees to identify two PMEL variants associated with heritable PDS/PG. PMEL (premelanosome protein) encodes a key component of the melanosome, the organelle essential for melanin synthesis, storage, and transport. Targeted screening of PMEL in three independent cohorts (n = 394) identified seven additional PDS/PG-associated non-synonymous variants. Five of the nine variants exhibited defective processing of the PMEL protein. In addition, analysis of PDS/PG-associated PMEL variants expressed in HeLa cells revealed structural changes to pseudomelanosomes indicating altered amyloid fibril formation in five of the nine variants. Introduction of 11 base-pair deletions to the homologous pmela in zebrafish by the CRISPR-Cas9 method caused profound pigmentation defects and enlarged anterior segments in the eye, further supporting PMEL's role in ocular pigmentation and function. Taken together, these data support a model in which missense PMEL variants represent dominant negative mutations that impair the ability of PMEL to form functional amyloid fibrils. While PMEL mutations have previously been shown to cause pigmentation and ocular defects in animals, this research is the first report of mutations in PMEL causing human disease.
Nwanaji-Enwerem JC, Wang W, Nwanaji-Enwerem O, Vokonas P, Baccarelli A, Weisskopf M, Herndon LW, Wiggs JL, Park SK, Schwartz J. Association of Long-term Ambient Black Carbon Exposure and Oxidative Stress Allelic Variants With Intraocular Pressure in Older Men. JAMA Ophthalmol 2018;Abstract
Importance: Elevated intraocular pressure is a major risk factor for glaucoma, a leading cause of irreversible blindness worldwide. Environmental air pollution has been suggested as a potential contributor to elevated intraocular pressure; however, no studies have demonstrated such an association to date. Objective: To investigate the association of long-term ambient black carbon exposure with intraocular pressure in community-dwelling older adults. Design, Setting, and Participants: This population-based analysis, conducted from October 18, 2017, through March 22, 2018, used data from the all-male, New England-based Normative Aging Study of the US Department of Veterans Affairs. The analysis included 419 older men with a total of 911 follow-up study visits between January 1, 2000, and December 30, 2011. Intraocular pressure was measured by Goldmann applanation tonometry during the study visits. Validated spatiotemporal models were used to generate 1-year black carbon exposure levels at the addresses of the participants. Main Outcomes and Measures: An independently developed genetic score approach was used to calculate allelic risk scores for 3 pathways associated with black carbon toxicity: endothelial function, oxidative stress, and metal processing. The associations among black carbon exposure, allelic risk scores, and intraocular pressure were explored using linear mixed-effects models. Results: All 419 participants were men with a mean (SD) age of 75.3 (6.9) years. The mean (SD) 1-year black carbon exposure was 0.51 (0.18) μg/m3, and the mean (SD) intraocular pressure for the left eye was 14.1 (2.8) mm Hg and for the right eye was 14.1 (3.0) mm Hg. Of the 911 visits, 520 (57.1%) had a high endothelial function allelic risk score, 644 (70.7%) had a high metal-processing allelic risk score, and 623 (68.4%) had a high oxidative stress allelic risk score. In fully adjusted linear mixed-effects models, the association of black carbon with intraocular pressure was greater in individuals with a high oxidative stress allelic score (β = 0.36; 95% CI, 0.003-0.73) compared with individuals with a low score (β = -0.35; 95% CI, -0.86 to 0.15). Conclusions and Relevance: Ambient black carbon exposure may be a risk factor for increased intraocular pressure in individuals susceptible to other biological oxidative stressors. If additional studies confirm these results, monitoring ambient black carbon exposure and physiological oxidative stress may prevent the development and progression of intraocular pressure-related disease.
Hoguet A, Chen PP, Junk AK, Mruthyunjaya P, Nouri-Mahdavi K, Radhakrishnan S, Takusagawa HL, Chen TC. The Effect of Anti-Vascular Endothelial Growth Factor Agents on Intraocular Pressure and Glaucoma A Report by the American Academy of Ophthalmology. Ophthalmology 2018;Abstract
PURPOSE: To assess the effect of intravitreal injections of anti-vascular endothelial growth factor (anti-VEGF) agents on immediate and long-term intraocular pressure (IOP) elevation and glaucoma. METHODS: Literature searches of the PubMed and Cochrane databases, last conducted in April 2018, yielded 253 unique citations. Of these, 41 met the inclusion criteria and were rated according to the strength of evidence. Two articles were rated level I, 17 were rated level II, and 15 were rated level III; an additional 7 were excluded owing to poor study design and lack of relevance to the topic under evaluation. RESULTS: The studies that reported on short-term IOP elevation (i.e., between 0 and 60 minutes) showed that an immediate increase in IOP is seen in all patients when measured between 0 and 30 minutes of intravitreal injection and that the IOP elevation decreases over time. The data on long-term IOP elevation were mixed; 7 studies reported that between 4% and 15% of patients developed sustained elevation of IOP at 9 to 24 months after injection, whereas 6 studies found no long-term change in IOP from 1 to 36 months after injection. Pretreatment with glaucoma medications, anterior chamber tap, vitreous reflux, longer intervals between injections, and longer axial lengths were associated with lower IOP elevations after injection. Data were mixed on the relationship between IOP rise and the type of intravitreal injection, number of intravitreal injections, pre-existing glaucoma, and globe decompression before injection. There were no data on the onset or progression of glaucoma in the studies reviewed in this assessment. CONCLUSIONS: Intravitreal injection of anti-VEGF agents results in an immediate and transient rise in IOP. A long-term increase in IOP may be seen as well, and further studies are needed to determine at-risk populations. Although there is some suggestion in the literature, there is currently insufficient data to determine the impact of intravitreal anti-VEGF injections on glaucoma progression. Even though pretreatment with glaucoma medications, performing anterior chamber paracentesis, or increasing the interval between injections may reduce the impact of transient IOP elevation, the clinical significance and associated risks of these interventions are unknown.

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