Glaucoma

Glaucoma Publications

Wu AM, Shen LQ. Racial Disparities Affecting Black Patients in Glaucoma Diagnosis and Management. Semin Ophthalmol 2023;:1-11.Abstract
Black patients are more affected by glaucoma and suffer from more advanced disease. Diagnostic challenges among black patients with glaucoma include lower rates of diagnostic testing and thinner average central corneal thickness, the latter of which affects intraocular pressure measurement. Treatment challenges include poor follow-up, medication adherence, and trust in providers. Black patients undergoing trabeculectomy have higher rates of failure compared to white patients. Race is not a definitive factor affecting success for tube shunts, laser trabeculoplasty, cyclophotocoagulation, and micro-invasive glaucoma surgeries, but the body of evidence is limited by low inclusion of black patients in these studies. Future steps should include increased attention toward improving trust between patients and providers, improving access to care, and increased representation of black patients in glaucoma research to better understand factors affecting racial disparities in glaucoma management and outcomes in this population disproportionately affected by the disease.
Wu AM, Shen LQ. Racial Disparities Affecting Black Patients In Glaucoma Diagnosis And Management. Semin Ophthalmol 2023;38(1):65-75.Abstract
Black patients are more affected by glaucoma and suffer from more advanced disease. Diagnostic challenges among black patients with glaucoma include lower rates of diagnostic testing and thinner average central corneal thickness, the latter of which affects intraocular pressure measurement. Treatment challenges include poor follow-up, medication adherence, and trust in providers. Black patients undergoing trabeculectomy have higher rates of failure compared to white patients. Race is not a definitive factor affecting success for tube shunts, laser trabeculoplasty, cyclophotocoagulation, and micro-invasive glaucoma surgeries, but the body of evidence is limited by low inclusion of black patients in these studies. Future steps should include increased attention toward improving trust between patients and providers, improving access to care, and increased representation of black patients in glaucoma research to better understand factors affecting racial disparities in glaucoma management and outcomes in this population disproportionately affected by the disease.
Marando CM, Chen TC. Evidence for Complementary and Alternative Therapies to Treat Glaucoma. Semin Ophthalmol 2023;38(1):85-91.Abstract
Complementary and alternative medicine is used by approximately 5% of patients with glaucoma, and examples include marijuana, Ginkgo biloba extract, bilberry fruit extract, and acupuncture. Systemic marijuana is not beneficial for glaucoma due to the short duration of action, the lack of evidence that it alters disease progression, and its negative side effect profile. Drops that affect the cannabinoid pathway are still being studied. Ginkgo biloba and bilberry fruit extracts have been shown to decrease oxidative stress and improve perfusion of the optic nerve head. However, these findings are inconsistent throughout the literature and the studies are small, which makes the overall evidence weak. There is no evidence that acupuncture alters glaucoma disease progression or causes a sustained decrease in intraocular pressure. In summary, the literature suggests that there are transient and/or theoretical benefits of complementary and alternative medicine for glaucoma care; however, the overall evidence to support their use is weak.
Ciociola EC, Yang S-A, Hall N, Lorch AC, Miller JW, Friedman DS, Boland MV, Elze T, Zebardast N, Zebardast N. Effectiveness of Trabeculectomy and Tube Shunt with versus without Concurrent Phacoemulsification: Intelligent Research in Sight Registry Longitudinal Analysis. Ophthalmol Glaucoma 2023;6(1):42-53.Abstract
OBJECTIVE: To determine the effectiveness of trabeculectomy and glaucoma drainage device (GDD) surgery performed with concurrent phacoemulsification compared with stand-alone procedures. DESIGN: Multicenter retrospective cohort study. PARTICIPANTS: Patients in the Intelligent Research in Sight Registry who underwent trabeculectomy or GDD from 2013 through 2019. METHODS: The Kaplan-Meier survival analysis was used to determine reoperation rates. Reoperation was defined as any subsequent glaucoma surgery occurring 1 month to 3 years after the initial procedure. Multivariable Cox proportional hazard models were used to determine reoperation risk factors. MAIN OUTCOME MEASURES: Reoperation rate, intraocular pressure (IOP), visual acuity, reoperation procedure type, postoperative complications, and predictors of surgical failure. RESULTS: A total of 117 697 eyes undergoing glaucoma surgery alone and 35 657 eyes undergoing surgery with phacoemulsification were included. The cumulative reoperation rates at postoperative years 1 and 3 were 4.9% and 11.5%, respectively, for trabeculectomy alone and 3.0% and 7.3%, respectively, for trabeculectomy combined with phacoemulsification (P < 0.001). The reoperation rates at postoperative 1 and 3 years were 3.8% and 7.8%, respectively, for GDD alone and 2.1% and 5.4%, respectively, for GDD with phacoemulsification (P < 0.001). Stand-alone procedures achieved greater IOP reduction by percentage change from baseline (trabeculectomy alone, 35.3% vs. trabeculectomy with phacoemulsification, 23.1%, P < 0.001; and GDD alone, 36.0% vs. GDD with phacoemulsification, 29.3%; P < 0.001). Visual acuity improved by 0.12 logarithm of the minimum angle of resolution (logMAR) (95% confidence interval [CI], 0.11-0.12) and 0.10 logMAR (95% CI, 0.08-0.11) after trabeculectomy and GDD with phacoemulsification and declined by 0.15 logMAR (95% CI, 0.14-0.15) and 0.12 logMAR (95% CI, 0.11-0.12) after stand-alone trabeculectomy and GDD. The overall documented complication rate was 2.9% for GDD and 1.4% for trabeculectomy. Age, sex, race, ethnicity, baseline IOP, and glaucoma diagnosis and severity were associated with surgical failure risk. The most common reoperation procedure was GDD. CONCLUSIONS: Reoperation rates within the first 3 years after trabeculectomy and GDD with and without phacoemulsification were low. Trabeculectomy and GDD with phacoemulsification had lower reoperation rates than those with stand-alone procedures. However, stand-alone procedures resulted in greater IOP reduction compared with combined procedures. Postoperative complications were uncommon overall. Patient age, sex, race, ethnicity, baseline IOP, and glaucoma diagnosis and severity were associated with surgical success.
Qiu M, Avdagic E, Ramulu PY, Golnik K, Boland MV. Ophthalmology Surgical Assessment of Tube Shunt Glaucoma Surgery. Ophthalmol Glaucoma 2023;6(1):100-105.Abstract
PURPOSE: To develop an internationally standardized and validated tool to assess skill in performing tube shunt surgery. DESIGN: A panel of 6 glaucoma surgeons developed a tool for assessing tube shunt surgery using a modified Dreyfus scale for skill acquisition. The tool was reviewed by a panel of 10 international content experts, and their comments were incorporated into the final rubric. PARTICIPANTS: A different panel of 8 international glaucoma specialists independently graded videos of surgical procedures performed by 6 surgeons at various levels of ophthalmic training. MAIN OUTCOME MEASURES: Inter-rater reliability for each step in the rubric was calculated. RESULTS: The tube shunt rubric contained 13 steps specific to tube shunt surgery and 7 global indices. The Cronbach α statistic, a measure of internal reliability, ranged from 0.75 to 0.97, indicating strong internal reliability for all 13 steps. CONCLUSIONS: The tube shunt assessment tool has face validity, content validity, and interobserver reliability, and can be used to assess tube shunt surgery skills. Further studies are required to determine predictive and construct validity.
Li S, Jakobs TC. Secreted phosphoprotein 1 slows neurodegeneration and rescues visual function in mouse models of aging and glaucoma. Cell Rep 2022;41(13):111880.Abstract
Aging causes an irreversible, cumulative decline in neuronal function. Using the visual system as a model, we show that astrocytes play a critical role in maintaining retinal ganglion cell health and that deletion of SPP1 (secreted phosphoprotein 1, or osteopontin) from astrocytes leads to increased vulnerability of ganglion cells to age, elevated intraocular pressure, and traumatic optic nerve damage. Overexpression of SPP1 slows the age-related decline in ganglion cell numbers and is highly protective of visual function in a mouse model of glaucoma. SPP1 acts by promoting phagocytosis and secretion of neurotrophic factors while inhibiting production of neurotoxic and pro-inflammatory factors. SPP1 up-regulates transcription of genes related to oxidative phosphorylation, functionally enhances mitochondrial respiration, and promotes the integrity of mitochondrial microstructure. SPP1 increases intracellular ATP concentration via up-regulation of VDAC1.
Fu H, Siggs OM, Knight LS, Staffieri SE, Ruddle JB, Birsner AE, Collantes ER, Craig JE, Wiggs JL, D'Amato RJ. Thrombospondin 1 missense alleles induce extracellular matrix protein aggregation and TM dysfunction in congenital glaucoma. J Clin Invest 2022;132(23)Abstract
Glaucoma is a highly heritable disease that is a leading cause of blindness worldwide. Here, we identified heterozygous thrombospondin 1 (THBS1) missense alleles altering p.Arg1034, a highly evolutionarily conserved amino acid, in 3 unrelated and ethnically diverse families affected by congenital glaucoma, a severe form of glaucoma affecting children. Thbs1R1034C-mutant mice had elevated intraocular pressure (IOP), reduced ocular fluid outflow, and retinal ganglion cell loss. Histology revealed an abundant, abnormal extracellular accumulation of THBS1 with abnormal morphology of juxtacanalicular trabecular meshwork (TM), an ocular tissue critical for aqueous fluid outflow. Functional characterization showed that the THBS1 missense alleles found in affected individuals destabilized the THBS1 C-terminus, causing protein misfolding and extracellular aggregation. Analysis using a range of amino acid substitutions at position R1034 showed that the extent of aggregation was correlated with the change in protein-folding free energy caused by variations in amino acid structure. Extracellular matrix (ECM) proteins, especially fibronectin, which bind to THBS1, also accumulated within THBS1 deposits. These results show that missense variants altering THBS1 p.Arg1034 can cause elevated IOP through a mechanism involving impaired TM fluid outflow in association with accumulation of aggregated THBS1 in the ECM of juxtacanalicular meshwork with altered morphology.
Sit AJ, Chen TC, Takusagawa HL, Rosdahl JA, Hoguet A, Chopra V, Richter GM, Ou Y, Kim SJ, WuDunn D. Corneal Hysteresis for the Diagnosis of Glaucoma and Assessment of Progression Risk: A Report by the American Academy of Ophthalmology. Ophthalmology 2022;Abstract
PURPOSE: To review the current published literature on the utility of corneal hysteresis (CH) to assist the clinician in the diagnosis of glaucoma or in the assessment of risk for disease progression in existing glaucoma patients. METHODS: Searches of the peer-reviewed literature in the PubMed database were performed through July 2022. The abstracts of 423 identified articles were examined to exclude reviews and non-English articles. After inclusion and exclusion criteria were applied, 19 articles were selected, and the panel methodologist rated them for level of evidence. Eight articles were rated level I, and 5 articles were rated level II. The 6 articles rated level III were excluded. RESULTS: Corneal hysteresis is lower in patients with primary open-angle glaucoma, primary angle-closure glaucoma, pseudoexfoliative glaucoma, and pseudoexfoliation syndrome compared with normal subjects. Interpretation of low CH in patients with high intraocular pressure (IOP) or on topical hypotensive medications is complicated by the influence of these parameters on CH measurements. However, CH is also lower in treatment-naïve, normal-tension glaucoma patients compared with normal subjects who have a similar IOP. In addition, lower CH is associated with an increased risk of progression of glaucoma based on visual fields or structural markers in open-angle glaucoma patients, including those with apparently well-controlled IOP. CONCLUSIONS: Corneal hysteresis is lower in glaucoma patients compared with normal subjects, and lower CH is associated with an increased risk of disease progression. However, a causal relationship remains to be demonstrated. Nevertheless, measurement of CH complements current structural and functional assessments in determining disease risk in glaucoma suspects and patients. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.
Saini C, Davies EC, Chodosh J, Shen LQ. Glaucoma in Patients With Endothelial Keratoplasty. Cornea 2022;41(12):1584-1599.Abstract
Endothelial keratoplasty (EK), including Descemet stripping endothelial keratoplasty and Descemet membrane endothelial keratoplasty, is now the most performed corneal transplant procedure in the United States. Intraocular pressure (IOP) elevation and glaucoma are common complications and can cause irreversible vision loss and corneal graft failure. This review will cover the incidence, risk factors, and management of glaucoma and IOP elevation after EK. Higher preoperative IOP, preoperative glaucoma, and certain indications for EK, such as bullous keratopathy, are associated with increased risk of glaucoma and glaucoma progression in patients undergoing EK. In addition, we summarize the studies assessing graft outcomes in EK patients with glaucoma or glaucoma surgery. Finally, we provide future directions to improve clinical care in EK patients with glaucoma.
Ichhpujani P, Rodrigues AM, Kumar S, Singh RB. Analysing the change in contrast sensitivity post-travoprost treatment in primary open-angle glaucoma patients using Spaeth Richman contrast sensitivity test. Int Ophthalmol 2022;Abstract
OBJECTIVE: To determine the ability of the Internet-based Spaeth/Richman Contrast Sensitivity (SPARCS) in assessing the change in contrast sensitivity (both central and peripheral) post-treatment with travoprost 0.004%. DESIGN: This is a prospective observational study. METHODS AND PARTICIPANTS: Data of 62 eyes (33 patients) undergoing treatment for naïve POAG patients were analysed. Patients were followed up for a period of six months after starting topical travoprost (Travatan 0.004%, Alcon), and the change in central and peripheral CS was studied. RESULTS: Mean total SPARCS score at baseline was 69 ± 10.99, improved to 74.62 ± 9.50 after 6 months of therapy (p: 0.001) in all the glaucoma severity groups. Mean SPARCS score at baseline in mild glaucoma group was 72.05 ± 9.87, in the moderate glaucoma group, it was 62.23 ± 9.2, and in the severe glaucoma group, it was 59.36 ± 11.65. After 6 months of treatment with travoprost, the CS improved to 76.05 ± 8.36 in mild group, 76.69 ± 8.82 in moderate group and 67.18 ± 11.15 in severe group (p value: 0.014). The percentage change in the CS from baseline showed significant improvement in the superotemporal quadrant at 1 month (p value: 0.032), superonasal quadrant (p value: 0.049), inferotemporal quadrant at 3 months (p value: 0.003) and 6 months (p value: 0.039). Inferonasal quadrant was affected most by glaucoma. A statistically significant correlation was seen between total SPARCS score with MD and PSD. Correlation was also seen between the percentage change in CS and average RNFL thickness at 3 and 6 months. CONCLUSION: Both central and peripheral CS improve following IOP reduction with travoprost. Change in the CS has a significant correlation with RNFL thickness and the perimetric indices.
Saini C, Davies EC, Ung L, Chodosh J, Ciolino JB, Jurkunas UV, Paschalis EI, Pineda R, Saeed HN, Yin J, Shen LQ. Incidence and risk factors for glaucoma development and progression after corneal transplantation. Eye (Lond) 2022;Abstract
OBJECTIVE: To assess the cumulative incidence and risk factors for glaucoma development and progression within 1-2 years following corneal transplant surgery. DESIGN: Retrospective cohort study. METHODS: Patients undergoing penetrating keratoplasty (PK), deep anterior lamellar keratoplasty (DALK), Descemet stripping endothelial keratoplasty (DSEK), Descemet membrane endothelial keratoplasty (DMEK), Boston keratoprosthesis type I (KPro) implantation, or endothelial keratoplasty (DSEK or DMEK) under previous PK (EK under previous PK) at one academic institution with at least 1 year of follow-up were included. Primary outcome measures were cumulative incidence of glaucoma development and progression after corneal transplant, in patients without and with preoperative glaucoma, respectively. Risk factors for glaucoma development and progression were also assessed. RESULTS: Four hundred and thirty-one eyes of 431 patients undergoing PK (113), DALK (17), DSEK (71), DMEK (168), KPro (35) and EK under previous PK (27) with a mean follow-up of 22.9 months were analyzed. The 1-year cumulative incidence for glaucoma development and progression was 28.0% and 17.8% in patients without and with preoperative glaucoma, respectively. In a Cox proportional hazards analysis, DSEK surgery, KPro implantation, average intraocular pressure (IOP) through follow-up and postoperative IOP spikes of ≥30 mmHg were each independently associated with glaucoma development or progression (p < 0.04 for all). CONCLUSIONS: A significant proportion of patients developed glaucoma or exhibited glaucoma progression within 1 year after corneal transplantation. Patient selection for DSEK may partly explain the higher risk for glaucoma in these patients. Postoperative IOP spikes should be minimized and may indicate the need for co-management with a glaucoma specialist.
Liang YB, Shen R, Zhou W, Fan S, Chan PP, Tham CCY, Congdon N, Friedman DS, Wang N. Prevalence and Ocular Biometric Characteristics of Myopia in Primary Angle Closure Disease in Rural China: The Handan Eye Study. Invest Ophthalmol Vis Sci 2022;63(12):19.Abstract
PURPOSE: The purpose of this study was to determine the prevalence of myopia among patients with primary angle closure disease (PACD) in rural China and their ocular biometric characteristics. METHODS: Study subjects were recruited from the Handan Eye Study. A/B-mode scan (Cine Scan, Quantel Medical, Cedex, France) was used to measure the axial length, anterior chamber depth (ACD), and lens thickness (LT). PACD was defined as the anterior chamber angle being considered closed when 180 degrees or more of the posterior pigmented trabecular meshwork were not visible on the gonioscopy. Myopia was defined as a spherical equivalent (SE) refractive error ≤-0.5 diopter (D). Persons who did not meet PACD definition were classified as the open-angle (OA) group. RESULTS: The overall prevalence of myopia in persons with PACD was 13.7% (11.6% in primary angle closure suspect [PACS], 21.6% in primary angle closure [PAC], 62.5% in primary angle closure glaucoma [PACG]). The age-specific prevalence of myopia in PACD eyes was 41.7% at 30 to 39 years old, 12.3% at 40 to 49 years old, 8.7% at 50 to 59 years old, 10.7% at 60 to 69 years old, and 31.7% at age 70 years and over. PACD had shorter AL (22.2 ± 0.8 vs. 22.9 ± 0.9 mm, P < 0.001), shallower ACD (2.3 ± 0.3 vs. 2.8 ± 0.4 mm, P < 0.001), and greater LT (5.0 ± 0.5 vs. 4.7 ± 0.5 mm, P < 0.001). PACD had even thicker lenses and deeper ACD with age than those with OA (all P ≤ 0.025) from 30 years to 70 years of age and over. CONCLUSIONS: Myopia was common among persons with PACD who were less than 40 years of age in this rural Chinese population, and over half of those with PACG were myopic.
Pitts KM, Neeson CE, Hall NE, Lin JB, Falah HK, Wang SL, Lo KT, Song CE, Margeta MA, Solá-Del Valle DA. Neurodegeneration Markers Galectin-3 and Apolipoprotein E Are Elevated in the Aqueous Humor of Eyes With Glaucoma. Transl Vis Sci Technol 2022;11(11):1.Abstract
PURPOSE: Galectin-3 (Gal-3) and apolipoprotein E (APOE) are markers of activated microglia in neurodegenerative diseases of the central nervous system, whose targeting is protective in mouse models of glaucoma. In this study, we examined levels of Gal-3 and APOE in human aqueous humor (AH) and defined their clinical associations with glaucoma. METHODS: We collected AH from 59 glaucoma patients and 15 controls at the start of planned ophthalmic surgery. Gal-3 and APOE levels were quantified by enzyme-linked immunosorbent assay. Total protein in AH was quantified by bicinchoninic acid assay. Significant associations between Gal-3, APOE, and clinical covariates were defined using univariate and multivariate linear regression models. RESULTS: Gal-3 and APOE levels were significantly elevated in the AH of glaucoma patients compared to controls (P = 0.004 and P < 0.001, respectively). Gal-3 and APOE were positively correlated across the entire cohort (r = 0.65, P = 6.2E-9). No association was observed between Gal-3 and total protein or APOE and total protein (P = 0.35 and P = 0.50, respectively), indicating that their levels were not increased in glaucomatous AH due to nonspecific protein accumulation. Multivariate linear regression modeling revealed significant associations between Gal-3 and maximum recorded intraocular pressure (P = 0.009) and between APOE and number of past ophthalmic surgeries (P = 0.031). CONCLUSIONS: We demonstrate that Gal-3 and APOE are significantly elevated in the AH of eyes with glaucoma and are associated with a history of poorly controlled disease. TRANSLATIONAL RELEVANCE: Gal-3 and APOE in AH may inform clinical decision-making as quantifiable readouts of microglial activation in eyes with glaucoma.
Xu C, Saini C, Wang M, Devlin J, Wang H, Greenstein SH, Brauner SC, Shen LQ. Combined Model of OCT Angiography and Structural OCT Parameters to Predict Paracentral Visual Field Loss in Primary Open-Angle Glaucoma. Ophthalmol Glaucoma 2022;Abstract
PURPOSE: To assess a model combining optical coherence tomography angiography (OCTA) and optical coherence tomography (OCT) parameters to predict the severity of paracentral visual field (VF) loss in primary open-angle glaucoma (POAG). DESIGN: Cross-sectional study. PARTICIPANTS: Forty-four patients with POAG and 42 control subjects underwent OCTA and OCT imaging with a swept-source OCT device. METHODS: The circumpapillary microvasculature was quantified for vessel density (cpVD) and flow (cpFlow) after delineation of Bruch's membrane opening and removal of large vessels. Retinal nerve fiber layer thickness (RNFLT) and Bruch's membrane opening-minimum rim width (BMO-MRW) were measured from structural OCT. Paracentral total deviation (PaTD) was defined as the average of the total deviation values within the central 10 degrees on Humphrey VF testing (24-2) for upper and lower hemifields. The OCT and OCTA parameters were measured in the affected hemisphere corresponding to the hemifield with lower PaTD for POAG patients. Models were created to predict affected PaTD based on RNFLT alone; RNFLT and BMO-MRW; OCTA alone; or RNFLT, BMO-MRW and OCTA parameters. The models were compared using coefficient of determination (r2) and Bayesian information criterion (BIC) score. BIC decrease of ≥6 indicates strong evidence for model improvement. MAIN OUTCOME MEASURES: Performance of models containing OCT and OCTA parameters in predicting PaTD. RESULTS: POAG and controls were similar in age and gender (65.9±9.5 years and 38.4% male overall, p≥0.56 for both). Average RNFLT, minimum RNFLT, average BMO-MRW, minimum BMO-MRW, cpVD, and cpFlow were all significantly lower (all p<0.001) in the affected hemisphere in POAG patients compared to controls. In POAG patients, the average mean deviation was -4.33±3.25 dB; the PaTD of the affected hemifield averaged -4.55±5.26 dB and correlated significantly with both OCTA and structural OCT parameters (r≥0.43, p≤0.004 for all). The model containing RNFLT, BMO-MRW, and OCTA parameters was superior in predicting affected PaTD (r2=0.47, BIC=290.7), with higher r2 and lower BIC compared to all three other models. CONCLUSIONS: A combined model of OCTA and structural OCT parameters can predict the severity of paracentral visual field loss of the affected hemifield, supporting clinical utility of OCTA in POAG patients with paracentral VF loss.

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