Glaucoma

Li S, Jakobs TC. Vitamin C protects retinal ganglion cells via SPP1 in glaucoma and after optic nerve damage. Life Sci Alliance 2023;6(8)Abstract
Glaucoma is a common neurodegenerative disorder characterized by retinal ganglion cell death, astrocyte reactivity in the optic nerve, and vision loss. Currently, lowering the intraocular pressure (IOP) is the first-line treatment, but adjuvant neuroprotective approaches would be welcome. Vitamin C possesses neuroprotective activities that are thought to be related to its properties as a co-factor of enzymes and its antioxidant effects. Here, we show that vitamin C promotes a neuroprotective phenotype and increases gene expression related to neurotropic factors, phagocytosis, and mitochondrial ATP production. This effect is dependent on the up-regulation of secreted phosphoprotein 1 (SPP1) in reactive astrocytes via the transcription factor E2F1. SPP1+ astrocytes in turn promote retinal ganglion cell survival in a mouse model of glaucoma. In addition, oral administration of vitamin C lowers the IOP in mice. This study identifies an additional neuroprotective pathway for vitamin C and suggests a potential therapeutic role of vitamin C in neurodegenerative diseases such as glaucoma.
Gutierrez A, Chen TC. Artificial intelligence in glaucoma: posterior segment optical coherence tomography. Curr Opin Ophthalmol 2023;34(3):245-254.Abstract
PURPOSE OF REVIEW: To summarize the recent literature on deep learning (DL) model applications in glaucoma detection and surveillance using posterior segment optical coherence tomography (OCT) imaging. RECENT FINDINGS: DL models use OCT derived parameters including retinal nerve fiber layer (RNFL) scans, macular scans, and optic nerve head (ONH) scans, as well as a combination of these parameters, to achieve high diagnostic accuracy in detecting glaucomatous optic neuropathy (GON). Although RNFL segmentation is the most widely used OCT parameter for glaucoma detection by ophthalmologists, newer DL models most commonly use a combination of parameters, which provide a more comprehensive approach. Compared to DL models for diagnosing glaucoma, DL models predicting glaucoma progression are less commonly studied but have also been developed. SUMMARY: DL models offer time-efficient, objective, and potential options in the management of glaucoma. Although artificial intelligence models have already been commercially accepted as diagnostic tools for other ophthalmic diseases, there is no commercially approved DL tool for the diagnosis of glaucoma, most likely in part due to the lack of a universal definition of glaucoma defined by OCT derived parameters alone (see Supplemental Digital Content 1 for video abstract, http://links.lww.com/COOP/A54 ).
Elhusseiny AM, Hassan AK, Azhari JO, Elkheniny FD, Chauhan MZ, Chang TC, VanderVeen DK, Oke I, Mansour M, Pakravan M, Shaarawy T, Sallam AB. Ahmed and Baerveldt Glaucoma Drainage Devices in Childhood Glaucoma: A Meta-Analysis. J Glaucoma 2023;32(8):686-694.Abstract
PRCIS: The effectiveness of Ahmed glaucoma valve (AGV) and Baerveldt glaucoma implant (BGI) was comparable in the management of childhood glaucoma over the long term despite initial better success rate with BGI. There were higher tube block and retraction rates in the BGI group and higher tube exposure rates in the AGV group. PURPOSE: To evaluate the outcomes and safety of AGV and BGI in childhood glaucoma. MATERIALS AND METHODS: We performed a systematic literature review of publications from 1990 to 2022 in PubMed, EMBASE, ClinicalTrials.gov, Ovid MEDLINE, Cochrane CENTRAL, and google scholar for studies evaluating AGV and BGI in childhood glaucoma. Primary outcome measures were intraocular pressure (IOP) reduction and glaucoma medication reduction. The secondary outcome measures were the success rates and incidence of postoperative complications. We conducted a meta-analysis using a random effects model. RESULTS: Thirty-two studies met the inclusion criteria. A total of 1480 eyes were included. The mean IOP reduction was 15.08 mm Hg ( P < 0.00001) for AGV and 14.62 ( P < 0.00001) for the BGI group. The mean difference between pre and postoperative glaucoma medications was 1 ( P < 0.00001) fewer medications in the AGV group and 0.95 ( P < 0.0001) fewer medications in the BGI group. There was a lower success rate in the AGV versus BGI groups at 2 years [63% vs 83%, respectively ( P < 0.0001) and 3 years (43% vs 79%, respectively ( P < 0.0001)]; however, the success was higher for AGV at 5 years (63% vs 56% in the BGI group, P < 0.001). The incidence of postoperative complications was comparable in the AGV and BGI groups, with rates of 28% and 27%, respectively. CONCLUSIONS: The IOP and glaucoma medication reduction, success rates, and incidence of postoperative complications were comparable in Ahmed and Baerveldt groups. Most literature comes from retrospective low-quality studies on refractory childhood glaucoma. Further larger cohort studies are needed.
Zeleznik OA, Kang JH, Lasky-Su J, Eliassen HA, Frueh L, Clish CB, Rosner BA, Elze T, Hysi P, Khawaja A, Wiggs JL, Pasquale LR, and Consortium UKBEV. Plasma metabolite profile for primary open-angle glaucoma in three US cohorts and the UK Biobank. Nat Commun 2023;14(1):2860.Abstract
Glaucoma is a progressive optic neuropathy and a leading cause of irreversible blindness worldwide. Primary open-angle glaucoma is the most common form, and yet the etiology of this multifactorial disease is poorly understood. We aimed to identify plasma metabolites associated with the risk of developing POAG in a case-control study (599 cases and 599 matched controls) nested within the Nurses' Health Studies, and Health Professionals' Follow-Up Study. Plasma metabolites were measured with LC-MS/MS at the Broad Institute (Cambridge, MA, USA); 369 metabolites from 18 metabolite classes passed quality control analyses. For comparison, in a cross-sectional study in the UK Biobank, 168 metabolites were measured in plasma samples from 2,238 prevalent glaucoma cases and 44,723 controls using NMR spectroscopy (Nightingale, Finland; version 2020). Here we show higher levels of diglycerides and triglycerides are adversely associated with glaucoma in all four cohorts, suggesting that they play an important role in glaucoma pathogenesis.
Bao YK, Xu BY, Friedman DS, Cho A, Foster PJ, Jiang Y, Porporato N, Pardeshi AA, Jiang Y, Munoz B, Aung T, He M. Biometric Risk Factors for Angle Closure Progression After Laser Peripheral Iridotomy. JAMA Ophthalmol 2023;141(6):516-524.Abstract
IMPORTANCE: Laser peripheral iridotomy (LPI) is the most common primary treatment for primary angle closure disease (PACD). However, there are sparse data guiding the longitudinal care of PAC suspect (PACS) eyes after LPI. OBJECTIVE: To elucidate the anatomic effects of LPI that are associated with a protective outcome against progression from PACS to PAC and acute angle closure (AAC) and to identify biometric factors that predict progression after LPI. DESIGN, SETTING, AND PARTICIPANTS: This was a retrospective analysis of data from the Zhongshan Angle Closure Prevention (ZAP) trial, a study of mainland Chinese people aged 50 to 70 years with bilateral PACS who received LPI in 1 randomly selected eye. Gonioscopy and anterior-segment optical coherence tomography (AS-OCT) imaging were performed 2 weeks after LPI. Progression was defined as the development of PAC or an acute angle closure (AAC) attack. Cohort A included a random mix of treated and untreated eyes, and cohort B included only eyes treated with LPI. Univariable and multivariable Cox regression models were developed to assess biometric risk factors for progression in cohorts A and B. Data were analyzed from January 4 to December 22, 2022. MAIN OUTCOME AND MEASURE: Six-year progression to PAC or AAC. RESULTS: Cohort A included 878 eyes from 878 participants (mean [SD] age, 58.9 [5.0] years; 726 female [82.7%]) of whom 44 experienced progressive disease. In a multivariable analysis, treatment (hazard ratio [HR], 0.67; 95% CI, 0.34-1.33; P = .25) was no longer associated with progression after adjusting for age and trabecular iris space area at 500 μm (TISA at 500 μm) at the 2-week visit. Cohort B included 869 treated eyes from 869 participants (mean [SD] age, 58.9 [5.0] years; 717 female [82.5%]) of whom 19 experienced progressive disease. In multivariable analysis, TISA at 500 μm (HR, 1.33 per 0.01 mm2 smaller; 95% CI, 1.12-1.56; P = .001) and cumulative gonioscopy score (HR, 1.25 per grade smaller; 95% CI, 1.03-1.52; P = .02) at the 2-week visit were associated with progression. Persistent angle narrowing on AS-OCT (TISA at 500 μm ≤0.05 mm2; HR, 9.41; 95% CI, 3.39-26.08; P <.001) or gonioscopy (cumulative score ≤6; HR, 2.80; 95% CI, 1.13-6.93; P =.04) conferred higher risk of progression. CONCLUSIONS AND RELEVANCE: Study results suggest that persistent angle narrowing detected by AS-OCT or cumulative gonioscopy score was predictive of disease progression in PACS eyes after LPI. These findings suggest that AS-OCT and gonioscopy may be performed to identify patients at high risk of developing angle closure who may benefit from closer monitoring despite patent LPI.
Yuan Y, Wang W, Xiong R, Zhang J, Li C, Yang S, Friedman DS, Foster PJ, He M. Fourteen-Year Outcome of Angle-Closure Prevention with Laser Iridotomy in the Zhongshan Angle-Closure Prevention Study: Extended Follow-up of a Randomized Controlled Trial. Ophthalmology 2023;130(8):786-794.Abstract
PURPOSE: This study aimed to evaluate the efficacy of laser peripheral iridotomy (LPI) prophylaxis for patients with primary angle-closure suspect (PACS) after 14 years and to identify risk factors for the conversion from PACS to primary angle closure (PAC). DESIGN: Extended follow-up of the Zhongshan Angle-Closure Prevention Study. PARTICIPANTS: Eight hundred eighty-nine Chinese patients 50 to 70 years of age with bilateral PACS. METHODS: Each patient received LPI in 1 randomly selected eye, with the fellow untreated eye serving as a control. Because the risk of glaucoma was low and acute angle closure (AAC) occurred only rarely, the follow-up was extended to 14 years despite substantial benefits of LPI reported after the 6-year visit. MAIN OUTCOME MEASURES: Incidence of PAC, a composite end point including peripheral anterior synechiae, intraocular pressure (IOP) of > 24 mmHg, or AAC. RESULTS: During the 14 years, 390 LPI-treated eyes and 388 control eyes were lost to follow-up. A total of 33 LPI-treated eyes and 105 control eyes reached primary end points (P < 0.01). Within them, 1 LPI-treated eye and 5 control eyes progressed to AAC. Primary angle-closure glaucoma was found in 2 LPI-treated eyes and 4 control eyes. The hazard ratio for progression to PAC was 0.31 (95% confidence interval, 0.21-0.46) in LPI-treated eyes compared with control eyes. At the 14-year visit, LPI-treated eyes showed more severe nuclear cataract, higher IOP, and larger angle width and limbal anterior chamber depth (LACD) than control eyes. Higher IOP, shallower LACD, and greater central anterior chamber depth (CACD) were associated with an increased risk of end points developing in control eyes. In the treated group, eyes with higher IOP, shallower LACD, or less IOP elevation after the darkroom prone provocative test (DRPPT) were more likely to demonstrate PAC after LPI. CONCLUIONS: Despite a two-third decrease in PAC occurrence after LPI, the cumulative risk of progression was relatively low in the community-based PACS population over 14 years. Apart from IOP, IOP elevation after DRPPT, CACD, and LACD, more risk factors are needed to achieve precise prediction of PAC occurrence and to guide clinical practice. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.
Kang J, De Arrigunaga S, Freeman SE, Zhao Y, Lin M, Liebman DL, Roldan AM, Kim JA, Chang DS, Friedman DS, Elze T. Comparison of Perimetric Outcomes from a Tablet Perimeter, Smart Visual Function Analyzer, and Humphrey Field Analyzer. Ophthalmol Glaucoma 2023;6(5):509-520.Abstract
PURPOSE: The tablet-based Melbourne Rapid Fields (MRF) visual field (VF) test and the IMOvifa Smart Visual Function Analyzer (SVFA) are portable perimeters that may allow for at-home monitoring and more frequent testing. We compared tablet and SVFA results with outputs from the Humphrey Field Analyzer (HFA) 24-2 Swedish Interactive Threshold Algorithm Standard program. DESIGN: Observational cross-sectional study. SUBJECTS: Adult participants with a diagnosis of glaucoma, suspected glaucoma, or ocular hypertension seen in the Massachusetts Eye and Ear glaucoma clinic were enrolled. All participants were reliable and experienced HFA testers. METHODS: Participants were tested with the SVFA and HFA. The study staff also trained participants on the MRF tablet with instructions to take weekly tests at home for 3 months. Visual field results from the 3 devices were compared. MAIN OUTCOME MEASURES: Mean deviation (MD), pattern standard deviation (PSD), reliability parameters, and point sensitivity. RESULTS: Overall, 79 participants (133 eyes) with a mean age of 61 ± 13 years (range, 26-79 years) were included; 59% of the participants were female, and the mean HFA MD was -2.7 ± 3.9 dB. The global indices of MD and PSD did not significantly vary between HFA and the 2 novel devices, except that the tablet VF reported a 0.6 dB higher PSD compared with HFA. However, tablet and SVFA sensitivities significantly differed from those of the HFA at 36 and 39 locations, respectively, out of 52 locations. Relative to HFA, the tablet overestimated light sensitivity in the nasal field while underestimating the temporal field. The SVFA generally underestimated light sensitivity, but its results were more similar to HFA results compared with the tablet. CONCLUSIONS: Although average MD values from the 2 novel devices suggest that they provide similar results to the HFA, point-by-point comparisons highlight notable deviations. Differences in specific point sensitivity values were significant, especially between the tablet and the other 2 devices. These differences may in part be explained by differences in the devices' normative databases as well as how MD is calculated. However, the tablet had substantial differences based on location, indicating that the tablet design itself may be responsible for differences in local sensitivities. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.
Liebman DL, Wen JC, Shen LQ. Detecting disease progression in mild, moderate and severe glaucoma. Curr Opin Ophthalmol 2023;34(2):168-175.Abstract
PURPOSE OF REVIEW: The purpose of this review is to examine contemporary techniques for detecting the progression of glaucoma. We provide a general overview of detection principles and review evidence-based diagnostic strategies and specific considerations for detecting glaucomatous progression in patients with mild, moderate and severe disease. RECENT FINDINGS: Diagnostic techniques and technologies for glaucoma have dramatically evolved in recent years, affording clinicians an expansive toolkit with which to detect glaucoma progression. Each stage of glaucoma, however, presents unique diagnostic challenges. In mild disease, either structural or functional changes can develop first in disease progression. In moderate disease, structural or functional changes can occur either in tandem or in isolation. In severe disease, standard techniques may fail to detect further disease progression, but such detection can still be measured using other modalities. SUMMARY: Detecting disease progression is central to the management of glaucoma. Glaucomatous progression has both structural and functional elements, both of which must be carefully monitored at all disease stages to determine when interventions are warranted.
Sun JA, Manz SN, Shen LQ. Glaucoma management in patients with penetrating keratoplasty or keratoprosthesis. Curr Opin Ophthalmol 2023;34(2):95-102.Abstract
PURPOSE OF REVIEW: Advances in surgical techniques and postoperative care have significantly improved rates of short-term complications following keratoplasty; however, glaucoma remains a highly prevalent long-term and potentially devastating complication for postkeratoplasty patients. In this review, we provide an overview of recent literature on glaucoma management in patients who have undergone penetrating keratoplasty or the Boston keratoprosthesis type I (KPro) implantation. RECENT FINDINGS: New research suggests an inflammatory cause underlying glaucoma following KPro. Accurate IOP measurement is difficult in patients postkeratoplasty; study of objective techniques such as PDCT or Tono-Pen in penetrating keratoplasty eyes and trans-palpebral Diaton tonometry in KPro eyes have shown promising results. Early glaucoma surgical intervention should be considered for patients undergoing penetrating keratoplasty and KPro. SUMMARY: Patients who have undergone penetrating keratoplasty or implantation of the Boston keratoprosthesis type I should be monitored frequently for elevated intraocular pressure and for other signs of glaucomatous optic nerve damage. Intraocular pressure elevation should be treated promptly either medically or surgically while minimizing risk to the corneal graft. Further research into inflammatory causes and other treatment modalities is promising for the long-term visual success in these patients.
Yang S-A, Ciociola EC, Mitchell W, Hall N, Lorch AC, Miller JW, Friedman DS, Boland MV, Elze T, Zebardast N, Zebardast N. Effectiveness of Microinvasive Glaucoma Surgery in the United States: Intelligent Research in Sight Registry Analysis 2013-2019. Ophthalmology 2023;130(3):242-255.Abstract
PURPOSE: To evaluate the effectiveness of microinvasive glaucoma surgery (MIGS) with and without concurrent phacoemulsification. DESIGN: Multicenter, retrospective cohort study. PARTICIPANTS: Patients in the Intelligent Research in Sight (IRIS®) Registry who underwent Xen gel stent (ab interno) implantation, endoscopic cyclophotocoagulation (ECP), or goniotomy or canaloplasty from 2013 through 2019. METHODS: Kaplan-Meier survival analysis was used to assess reoperation rates. We defined reoperation as any subsequent glaucoma surgery occurring 1 month to 3 years after the initial procedure. Multivariable Cox proportional hazard models were used to determine factors predictive of reoperation. MAIN OUTCOME MEASURES: Reoperation rate, mean intraocular pressure (IOP) and visual acuity (VA), postoperative complications, predictors of reoperation, and reoperation procedure type. RESULTS: A total of 79 363 eyes from 57 561 patients were included, with 15 118 eyes (19%) receiving stand-alone MIGS and 64 245 eyes (81%) receiving MIGS concurrent with phacoemulsification. Overall, patients who underwent MIGS concurrently with phacoemulsification showed lower reoperation rates compared with stand-alone MIGS, most pronounced in ECP and goniotomy or canaloplasty. At postoperative year 2, the cumulative reoperation rate for stand-alone procedures was 15% for ECP, 24% for Xen implantation, and 24% for goniotomy or canaloplasty compared with 3% for ECP, 19% for Xen implantation, and 6% for goniotomy or canaloplasty concurrent with phacoemulsification (P < 0.001 for each stand-alone MIGS vs. MIGS with phacoemulsification). Black race, older age, moderate and severe glaucoma, higher baseline IOP, and glaucoma subtype were associated with higher reoperation risk. Although IOP decreased in all groups, stand-alone MIGS showed a more substantial decrease in mean IOP. Complication rates from MIGS were low overall: 1% for ECP, 1% for Xen implantation, and 2% for goniotomy or canaloplasty. CONCLUSIONS: In current United States clinical practice, MIGS has substantially lower reoperation rates when performed with phacoemulsification, especially for ECP and goniotomy or canaloplasty. Approximately one-sixth of patients undergoing stand-alone ECP and one-quarter of patients undergoing stand-alone Xen implantation or goniotomy or canaloplasty require reoperation by 2 years. Black race, diagnosis coding of moderate to severe glaucoma, and higher baseline IOP were associated with higher risk of reoperation after MIGS procedures. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.
Nirappel A, Klug E, Neeson C, Chachanidze M, El Helwe H, Hall N, Chang TC, Shen LQ, Solá-Del Valle D. Transscleral vs endoscopic cyclophotocoagulation: safety and efficacy when combined with phacoemulsification. BMC Ophthalmol 2023;23(1):129.Abstract
PURPOSE: To compare the effectiveness and safety of phacoemulsification combined with endoscopic cyclophotocoagulation (phaco/ECP), phacoemulsification combined with MicroPulse transscleral cyclophotocoagulation (phaco/MP-TSCPC), and phacoemulsification alone (phaco) in the treatment of coexisting cataract and glaucoma. METHODS: Retrospective cohort study of consecutive cases at Massachusetts Eye & Ear. The main outcome measures were the cumulative probabilities of failure between the phaco/ECP group, phaco/MP-TSCPC group, and the phaco alone group with failure defined as reaching NLP vision at any point postoperatively, undergoing additional glaucoma surgery, or the inability to maintain ≥ 20% IOP reduction from baseline with IOP between 5-18 mmHg while maintaining ≤ baseline medications. Additional outcome measures included changes in average IOP, number of glaucoma medications, and complication rates. RESULTS: Sixty-four eyes from 64 patients (25 phaco/ECP, 20 phaco/MPTSCPC, 19 phaco alone) were included in this study. The groups did not differ in age (mean 71.04 ± 6.7 years) or length of follow-up time. Baseline IOPs were significantly different between groups (15.78 ± 4.7 mmHg phaco/ECP, 18.37 ± 4.6 mmHg phaco/MP-TSCPC, 14.30 ± 4.2 mmHg phaco alone, p = 0.02). Primary open-angle glaucoma was the most common type of glaucoma in the phaco alone (42%) and phaco/ECP (48%) groups while mixed-mechanism glaucoma was the most common type in the phaco/MP-TSCPC group (40%). Surgical failure was less likely in eyes in the phaco/MP-TSCPC (3.40 times, p = 0.005) and phaco/ECP (1.40 times, p = 0.044) groups compared to phaco alone based on the Kaplan-Meier survival criteria. These differences maintained statistical significance when differences in preoperative IOP were taken into account using the Cox PH model (p = 0.011 and p = 0.004, respectively). Additionally, surgical failure was 1.98 times less likely following phaco/MP-TSCPC compared to phaco/ECP (p = 0.038). This difference only approached significance once differences in preoperative IOP were accounted for (p = 0.052). There was no significant difference in IOP reduction at 1 year between groups. Mean IOP reductions at 1 year were 3.07 ± 5.3 mmHg from a baseline of 15.78 ± 4.7 in the phaco/ECP group, 6.0 ± 4.3 mmHg from a baseline of 18.37 ± 4.6 in the phaco/MP-TSCPC group and 1.0 ± 1.6 from a baseline of 14.30 ± 4.2 mmHg in the phaco alone group. There were no differences in complication rates among the three groups. CONCLUSIONS: Both Phaco/MP-TSCPC and phaco/ECP appear to provide superior efficacy for IOP control when compared to phaco alone. All three procedures had similar safety profiles.
Ong AY, McCann P, Perera SA, Lim F, Ng SM, Friedman DS, Chang D. Lens extraction versus laser peripheral iridotomy for acute primary angle closure. Cochrane Database Syst Rev 2023;3(3):CD015116.Abstract
BACKGROUND: Acute primary angle closure (APAC) is a potentially blinding condition. It is one of the few ophthalmic emergencies and carries high rates of visual morbidity in the absence of timely intervention. Laser peripheral iridotomy (LPI) has been the standard of care thus far. However, LPI does not eliminate the long-term risk of chronic angle closure glaucoma and other associated sequelae. There has been increasing interest in lens extraction as the primary treatment for the spectrum of primary angle closure disease, and it is as yet unclear whether these results can be extrapolated to APAC, and whether lens extraction provides better long-term outcomes. We therefore sought to evaluate the effectiveness of lens extraction in APAC to help inform the decision-making process.  OBJECTIVES: To assess the effect of lens extraction compared to LPI in the treatment of APAC. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (which contains the Cochrane Eyes and Vision Trials Register) (2022, Issue 1), Ovid MEDLINE, Ovid MEDLINE E-pub Ahead of Print, Ovid MEDLINE In-Process and Other Non-Indexed Citations, Ovid MEDLINE Daily (January 1946 to 10 January 2022), Embase (January 1947 to 10 January 2022), PubMed (1946 to 10 January 2022), Latin American and Caribbean Health Sciences Literature Database (LILACS) (1982 to 10 January 2022), ClinicalTrials.gov, and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP). We did not use any date or language restrictions in the electronic search. We last searched the electronic databases on 10 January 2022. SELECTION CRITERIA: We included randomized controlled clinical trials comparing lens extraction against LPI in adult participants ( ≥ 35 years) with APAC in one or both eyes. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methodology and assessed the certainty of the body of evidence for prespecified outcomes using the GRADE approach. MAIN RESULTS: We included two studies conducted in Hong Kong and Singapore, comprising 99 eyes (99 participants) of predominantly Chinese origin. The two studies compared LPI with phacoemulsification performed by experienced surgeons. We assessed that both studies were at high risk of bias. There were no studies evaluating other types of lens extraction procedures.  Phacoemulsification may result in an increased proportion of participants with intraocular pressure (IOP) control compared with LPI at 18 to 24 months (risk ratio (RR) 1.66, 95% confidence interval (CI) 1.28 to 2.15; 2 studies, n = 97; low certainty evidence) and may reduce the need for further IOP-lowering surgery within 24 months (RR 0.07, 96% CI 0.01 to 0.51; 2 studies, n = 99; very low certainty evidence). Phacoemulsification may result in a lower mean IOP at 12 months compared to LPI (mean difference (MD) -3.20, 95% CI -4.79 to -1.61; 1 study, n = 62; low certainty evidence) and a slightly lower mean number of IOP-lowering medications at 18 months (MD -0.87, 95% CI -1.28 to -0.46; 1 study, n = 60; low certainty evidence), but this may not be clinically significant. Phacoemulsification may have little to no effect on the proportion of participants with one or more recurrent APAC episodes in the same eye (RR 0.32, 95% CI 0.01 to 7.30; 1 study, n = 37; very low certainty evidence). Phacoemulsification may result in a wider iridocorneal angle assessed by Shaffer grading at six months (MD 1.15, 95% CI 0.83 to 1.47; 1 study, n = 62; very low certainty evidence). Phacoemulsification may have little to no effect on logMAR best-corrected visual acuity (BCVA) at six months (MD -0.09, 95% CI -0.20 to 0.02; 2 studies, n = 94; very low certainty evidence). There was no evidence of a difference in the extent of peripheral anterior synechiae (PAS) (clock hours) between intervention arms at 6 months (MD -1.86, 95% CI -7.03 to 3.32; 2 studies, n = 94; very low certainty evidence), although the phacoemulsification group may have less PAS (degrees) at 12 months (MD -94.20, 95% CI -140.37 to -48.03; 1 study, n = 62) and 18 months (MD -127.30, 95% CI -168.91 to -85.69; 1 study, n = 60).  In one study, there were 26 adverse events in the phacoemulsification group: intraoperative corneal edema (n = 12), posterior capsular rupture (n = 1), intraoperative bleeding from iris root (n = 1), postoperative fibrinous anterior chamber reaction (n = 7), and visually significant posterior capsular opacification (n = 5), and no cases of suprachoroidal hemorrhage or endophthalmitis. There were four adverse events in the LPI group: closed iridotomy (n = 1) and small iridotomies that required supplementary laser (n = 3). In the other study, there was one adverse event in the phacoemulsification group (IOP > 30 mmHg on day 1 postoperatively (n = 1)), and no intraoperative complications. There were five adverse events in the LPI group: transient hemorrhage (n = 1), corneal burn (n = 1), and repeated LPI because of non-patency (n = 3).  Neither study reported health- or vision-related quality of life measures. AUTHORS' CONCLUSIONS: Low certainty evidence suggests that early lens extraction may produce more favorable outcomes compared to initial LPI in terms of IOP control. Evidence for other outcomes is less clear. Future high-quality and longer-term studies evaluating the effects of either intervention on the development of glaucomatous damage and visual field changes as well as health-related quality of life measures would be helpful.
Hanyuda A, Rosner BA, Wiggs JL, Negishi K, Pasquale LR, Kang JH. Long-term Alcohol Consumption and Risk of Exfoliation Glaucoma or Glaucoma Suspect Status among United States Health Professionals. Ophthalmology 2023;130(2):187-197.Abstract
PURPOSE: To assess the association between intakes of total alcohol and individual alcoholic beverages and the incidence of exfoliation glaucoma/glaucoma suspect (XFG/XFGS) status. DESIGN: Prospective cohort study. PARTICIPANTS: A total of 195 408 participants in the Nurses' Health Study (1980-2018), the Health Professionals Follow-up Study (1986-2018), and the Nurses' Health Study II (1991-2019) were followed biennially. Eligible participants at each 2-year risk period were ≧ 40 years and free of XFG/XFGS status with available data on diet and ophthalmic examination findings. METHODS: Cumulatively averaged total (primary exposure) and individual alcoholic beverage (beer, wine, and liquor) intakes from validated dietary information every 2-4 years. MAIN OUTCOME MEASURES: Confirmed incident XFG/XFGS status using medical records. We used per-eye Cox proportional hazards models, accounting for intereye correlations, to estimate multivariate-adjusted relative risks (MVRRs) and 95% confidence intervals (CIs). RESULTS: During 6 877 823 eye-years of follow-up, 705 eyes with XFG/XFGS status were documented. Greater total alcohol consumption was associated significantly with higher XFG/XFGS status risk: the MVRR for XFG/XFGS status for cumulatively averaged alcohol consumption of ≧15 g/day or more versus nondrinking was 1.55 (95% CI, 1.17-2.07; P = 0.02 for trend). Long- and short-term alcohol intake was associated significantly with XFG/XFGS status risk, with the strongest associations with cumulatively averaged alcohol intake as of 4 years before diagnosis (MVRR ≥ 15 g/day vs. nondrinking, 1.65; 95% CI, 1.25-2.18; P = 0.002 for trend). Compared with nondrinkers, consuming ≧ 3.6 drinks of beer, wine, or liquor per week was associated with the following MVRRs for XFG/XFGS status: 1.26 (95% CI, 0.89-1.77; P = 0.40 for trend), 1.30 (95% CI, 1.00-1.68; P = 0.15 for trend), and 1.46 (95% CI, 1.15-1.85; P = 0.01 for trend), respectively. We did not observe interactions by age, latitude, residential tier, or intakes of folate or vitamin A (P > 0.40 for interaction); however, the association between alcohol and XFG/XFGS status was suggestively stronger for those without a family history of glaucoma (P = 0.10 for interaction). CONCLUSIONS: Long-term alcohol consumption was associated with a higher risk of XFG/XFGS status. Our findings provide further clues regarding the XFG/XFGS etiology.
Tran JH, Stuart KV, de Vries V, Vergroesen JE, Cousins CC, Hysi PG, Do R, Rocheleau G, Kang JH, Wiggs JL, Macgregor S, Khawaja AP, Mackey DA, Klaver CCW, Ramdas WD, Pasquale LR, and for the UK Biobank Eye and Vision Consortium IGGC. Genetic Associations Between Smoking- and Glaucoma-Related Traits. Transl Vis Sci Technol 2023;12(2):20.Abstract
PURPOSE: The purpose of this study was to describe the genetic relationship between smoking and glaucoma. METHODS: We used summary-level genetic data for smoking initiation, smoking intensity (cigarettes per day [CPD]), intraocular pressure (IOP), vertical cup-disc ratio, and open-angle glaucoma (OAG) to estimate global genetic correlations (rg) and perform two-sample Mendelian randomization (MR) experiments that explored relations between traits. Finally, we examined associations between smoking genetic risk scores (GRS) and smoking traits with measured IOP and OAG in Rotterdam Study participants. RESULTS: We identified weak inverse rg between smoking- and glaucoma-related traits that were insignificant after Bonferroni correction. However, MR analysis revealed that genetically predicted smoking initiation was associated with lower IOP (-0.18 mm Hg per SD, 95% confidence interval [CI] = -0.30 to -0.06, P = 0.003). Furthermore, genetically predicted smoking intensity was associated with decreased OAG risk (odds ratio [OR] = 0.74 per SD, 95% CI = 0.61 to 0.90, P = 0.002). In the Rotterdam Study, the smoking initiation GRS was associated with lower IOP (-0.09 mm Hg per SD, 95% CI = -0.17 to -0.01, P = 0.04) and lower odds of OAG (OR = 0.84 per SD, 95% CI = 0.73 to 0.98, P = 0.02) in multivariable-adjusted analyses. In contrast, neither smoking history nor CPD was associated with IOP (P ≥ 0.38) or OAG (P ≥ 0.54). Associations between the smoking intensity GRS and glaucoma traits were null (P ≥ 0.13). CONCLUSIONS: MR experiments and GRS generated from Rotterdam Study participants support an inverse relationship between smoking and glaucoma. TRANSLATIONAL RELEVANCE: Understanding the genetic drivers of the inverse relationship between smoking and glaucoma could yield new insights into glaucoma pathophysiology.
Aboobakar IF, Kinzy TG, Zhao Y, Fan BJ, Pasquale LR, Qassim A, Kolovos A, Schmidt JM, Craig JE, Bailey JCN, Wiggs JL, Wiggs JL. Mitochondrial TXNRD2 and ME3 genetic risk scores are associated with specific primary open-angle glaucoma phenotypes. Ophthalmology 2023;Abstract
PURPOSE: Genetic variants in regions that include the mitochondrial genes TXNRD2 and ME3 are associated with primary open-angle glaucoma (POAG) in genome-wide association studies (GWAS). To assess their clinical impact, we investigated whether TXNRD2 and ME3 genetic risk scores (GRSs) are associated with specific glaucoma phenotypes. DESIGN: Cross-sectional study PARTICIPANTS: 2617 POAG cases and 2634 controls from the NEIGHBORHOOD consortium. METHODS: All POAG-associated single nucleotide polymorphisms (SNPs) in the TXNRD2 and ME3 loci were identified using GWAS data (p<0.05). Of these, 20 TXNRD2 and 24 ME3 SNPs were selected after adjusting for linkage disequilibrium. The correlation between SNP effect size and gene expression levels was investigated using the Gene-Tissue Expression (GTEx) database. GRSs were constructed for each individual using the unweighted sum of TXNRD2, ME3, and TXNRD2+ME3 combined risk alleles. Age and gender-adjusted odds ratios (ORs) for POAG diagnosis were calculated per decile for each GRS. Additionally, the clinical features of POAG cases in the top 1, 5, and 10% of each GRS were compared to the bottom 1, 5, and 10%, respectively. MAIN OUTCOME MEASURES: POAG OR per GRS decile; maximal treated intraocular pressure (IOP) and prevalence of paracentral visual field loss among POAG cases with high vs. low GRSs. RESULTS: Increased SNP effect size strongly correlated with higher TXNRD2 and lower ME3 expression levels (r=0.95 and -0.97, respectively, p<0.05 for both). Individuals in decile 10 of TXNRD2+ME3 GRS had the highest odds of POAG diagnosis (OR=1.79 compared to decile 1, p<0.001). POAG cases in the top 1% of TXNRD2 GRS had higher mean maximal treated IOP compared to the bottom 1% (19.9 mmHg vs 15.6 mmHg, adjusted p=0.03). POAG cases in the top 1% of ME3 and TXNRD2+ME3 GRS had a higher prevalence of paracentral field loss compared to the bottom 1% (72.7-88.9% vs 14.3-33.3%; adjusted p=0.03 for both). CONCLUSIONS: POAG patients with higher TXNRD2 and ME3 GRSs had higher treated IOP and a greater prevalence of paracentral field loss. Functional studies exploring how these variants impact mitochondrial function in glaucoma patients are warranted.

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