Oberfeld B, Golsoorat Pahlaviani F, Hall N, Falah-Trzcinski H, Trzcinski J, Chang T, Solá-Del Valle D.
Combined MIGS: Comparing Additive Effects of Phacoemulsification, Endocyclophotocoagulation, and Kahook Dual Blade. Clin Ophthalmol 2023;(17):1647-1659.
Oh D-J, Kang MH, Ooi YH, Choi KR, Sage HE, Rhee DJ.
Overexpression of SPARC in human trabecular meshwork increases intraocular pressure and alters extracellular matrix. Invest Ophthalmol Vis Sci 2013;54(5):3309-19.
AbstractPURPOSE: Intraocular pressure (IOP) regulation is largely unknown. SPARC-null mice demonstrate a lower IOP resulting from increased outflow. SPARC is a matricellular protein often associated with fibrosis. We hypothesized that SPARC overexpression would alter IOP by affecting extracellular matrix (ECM) synthesis and/or turnover in the trabecular meshwork (TM). METHODS: An adenoviral vector containing human SPARC was used to increase SPARC expression in human TM endothelial cells and perfused human anterior segments using multiplicities of infection (MOIs) 25 or 50. Total RNA from TM was used for quantitative PCR, while protein from cell lysates and conditioned media were used for immunoblot analyses and zymography. After completion of perfusion, the anterior segments were fixed, sectioned, and examined by light and confocal microscopy. RESULTS: SPARC overexpression increased the IOP of perfused human anterior segments. Fibronectin and collagens IV and I protein levels were elevated in both TM cell cultures and within the juxtacanalicular (JCT) region of perfused anterior segments. Collagen VI and laminin protein levels were increased in TM cell cultures but not in perfused anterior segments. The protein levels of pro-MMP-9 decreased while the kinetic inhibitors of metalloproteinases, TIMP-1 and PAI-1 protein levels, increased at MOI 25. At MOI 50, the protein levels of pro-MMP-1, -3, and -9 also decreased while PAI-1 and TIMP-1 and -3 increased. Only MMP-9 activity was decreased on zymography. mRNA levels of the collagens, fibronectin, and laminin were not affected by SPARC overexpression. CONCLUSIONS: SPARC overexpression increases IOP in perfused cadaveric human anterior segments resulting from a qualitative change the JCT ECM. Selective decrease of MMP-9 activity is likely part of the mechanism. SPARC is a regulatory node for IOP.
Ojha P, Wiggs JL, Pasquale LR.
The genetics of intraocular pressure. Semin Ophthalmol 2013;28(5-6):301-5.
AbstractGlaucoma is a leading cause of irreversible blindness. Intraocular pressure (IOP) is the only modifiable risk factor for glaucoma, yet there is little known about the molecular events that regulate IOP. Genetic and genomic studies have helped identify genes that influence IOP and could lead to the identification of biological pathways that serve as targets for novel pressure-modifying therapies. Genetic linkage studies resulted in the identification of several genes that cause Mendelian (autosomal dominant or autosomal recessive) forms of high-pressure glaucoma, including MYOC. PITX2, FOXC1, and CYP1B1. Classical twin studies suggest that IOP is a heritable trait. More recently, genome-wide association studies (GWAS) have shown that common genetic variants in the GAS7 and TMCO1 genomic regions are associated with elevated IOP. TMCO1 has also been associated with primary open-angle glaucoma in patients with advanced disease. A further study identifying additional genes contributing to IOP will be necessary to fully define the underlying genetic architecture of IOP.
Oke I, Badami A, Kosteva KL, Wu K, Desai MA.
Systemic Barriers in Receiving Electronically Prescribed Glaucoma Medications. J Glaucoma 2022;31(10):812-815.
AbstractPRCIS: Over a third of electronically prescribed glaucoma medications were not picked up within 1 month of patient request. Feedback-driven protocols may help minimize treatment interruptions attributed to electronic prescribing. PURPOSE: Glaucoma treatment relies on long-term medication compliance and many socioeconomic factors impact the ability of patients to receive their medications. This study aims to quantify treatment interruptions attributable to electronically prescribed medications and propose interventions to minimize this barrier. METHODS: This is a cross-sectional study of the electronic prescribing patterns at a tertiary care hospital serving a socioeconomically diverse patient population. Glaucoma medication refill requests received over a 6-week interval were reviewed and patient pharmacies were contacted 1 month after the request date to determine whether the medication was received by the patient. Patients who did not pick up the prescriptions were contacted and consented to participate in a survey to identify the barriers to acquiring the medications. RESULTS: Refill requests of 198 glaucoma medications met the inclusion criteria and the most common classes were prostaglandin analogs (44%) and alpha-2-agonists (21%). Medications were not obtained within 1 month in 71 (35.9%) cases. Prior authorization requirement was significantly associated with patients not obtaining their medication (odds ratio, 0.07; 95% confidence interval, 0.03-0.45). Patient reported challenges to successful receipt electronically prescribed medications included insurance coverage (32.2%) and pharmacy availability (22.6%). CONCLUSIONS: Approximately a third of electronically prescribed glaucoma medications were not received by patients within a month of refill request due to the need for prior authorization, insurance coverage, and pharmacy availability. A mechanism to alert providers and to address these barriers to medication access may minimize treatment interruption and disease progression.
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.
AbstractBACKGROUND: 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.
Ong AY, Ng SM, Vedula SS, Friedman DS.
Lens extraction for chronic angle-closure glaucoma. Cochrane Database Syst Rev 2021;3:CD005555.
AbstractBACKGROUND: Primary angle-closure glaucoma (PACG) is characterized by a rise in intraocular pressure (IOP) secondary to aqueous outflow obstruction, with relative pupillary block being the most common underlying mechanism. There is increasing evidence that lens extraction may relieve pupillary block and thereby improve IOP control. As such, comparing the effectiveness of lens extraction against other commonly used treatment modalities can help inform the decision-making process. OBJECTIVES: To assess the effectiveness of lens extraction compared with other interventions in the treatment of chronic PACG in people without previous acute angle-closure attacks. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, one other database, and two trials registers (December 2019). We also screened the reference lists of included studies and the Science Citation Index database. We had no date or language restrictions. SELECTION CRITERIA: We included randomized controlled trials (RCTs) comparing lens extraction with other treatment modalities for chronic PACG. DATA COLLECTION AND ANALYSIS: We followed standard Cochrane methodology. MAIN RESULTS: We identified eight RCTs with 914 eyes. We obtained data for participants meeting our inclusion criteria for these studies (PACG only, no previous acute angle-closure attacks), resulting in 513 eyes included in this review. The participants were recruited from a diverse range of countries. We were unable to conduct meta-analyses due to different follow-up periods and insufficient data. One study compared phacoemulsification with laser peripheral iridotomy (LPI) as standard care. Participants in the phacoemulsification group were less likely to experience progression of visual field loss (odds ratio [OR] 0.35, 95% confidence interval [CI] 0.13 to 0.91; 216 eyes; moderate certainty evidence), and required fewer IOP-lowering medications (mean difference [MD] -0.70, 95% CI -0.89 to -0.51; 263 eyes; moderate certainty evidence) compared with standard care at 12 months. Moderate certainty evidence also suggested that phacoemulsification improved gonioscopic findings at 12 months or later (MD -84.93, 95% CI -131.25 to -38.61; 106 eyes). There was little to no difference in health-related quality of life measures (MD 0.04, 95% CI -0.16 to 0.24; 254 eyes; moderate certainty evidence), and visual acuity (VA) (MD 2.03 ETDRS letter, 95% CI -0.77 to 4.84; 242 eyes) at 12 months, and no observable difference in mean IOP (MD -0.03mmHg, 95% CI -2.34 to 2.32; 257 eyes; moderate certainty evidence) compared to standard care. Irreversible loss of vision was observed in one participant in the phacoemulsification group, and three participants in standard care at 36 months (moderate-certainty evidence). One study (91 eyes) compared phacoemulsification with phaco-viscogonioplasty (phaco-VGP). Low-certainty evidence suggested that fewer IOP-lowering medications were needed at 12 months with phacoemulsification (MD -0.30, 95% CI -0.55 to -0.05). Low-certainty evidence also suggested that phacoemulsification may have improved gonioscopic findings at 12 months or later compared to phaco-VGP (angle grading MD -0.60, 95% CI -0.91 to -0.29; TISA500 MD -0.03, 95% CI -0.06 to -0.01; TISA750 MD -0.03, 95% CI -0.06 to -0.01; 91 eyes). Phacoemulsification may result in little to no difference in best corrected VA at 12 months (MD -0.01 log MAR units, 95% CI -0.10 to 0.08; low certainty evidence), and the evidence is very uncertain about its effect on IOP at 12 months (MD 0.50 mmHg, 95% CI -2.64 to 3.64; very low certainty evidence). Postoperative fibrin reaction was observed in two participants in the phacoemulsification group and four in the phaco-VGP group. Three participants in the phaco-VGP group experienced hyphema. No data were available for progression of visual field loss and quality of life measurements at 12 months. Two studies compared phacoemulsification with phaco-goniosynechialysis (phaco-GSL). Low-certainty evidence suggested that there may be little to no difference in mean IOP at 12 months (MD -0.12 mmHg, 95% CI -4.72 to 4.48; 1 study, 32 eyes) between the interventions. Phacoemulsification did not reduce the number of IOP-lowering medications compared to phaco-GSL at 12 months (MD -0.38, 95% CI -1.23 to 0.47; 1 study, 32 eyes; moderate certainty evidence). Three eyes in the phaco-GSL group developed hyphemas. No data were available at 12 months for progression of visual field loss, gonioscopic findings, visual acuity, and quality of life measures. Three studies compared phacoemulsification with combined phaco-trabeculectomy, but the data were only available for one study (63 eyes). In this study, low-certainty evidence suggested that there was little to no difference between groups in mean change in IOP from baseline (MD -0.60 mmHg, 95% CI -1.99 to 0.79), number of IOP-lowering medications at 12 months (MD 0.00, 95% CI -0.42 to 0.42), and VA measured by the Snellen chart (MD -0.03, 95% CI -0.18 to 0.12). Participants in the phacoemulsification group had fewer complications (risk ratio [RR] 0.59, 95% CI 0.34 to 1.04), and the phaco-trabeculectomy group required more IOP-lowering procedures (RR 5.81, 95% CI 1.41 to 23.88), but the evidence was very uncertain. No data were available for other outcomes. AUTHORS' CONCLUSIONS: Moderate certainty evidence showed that lens extraction has an advantage over LPI in treating chronic PACG with clear crystalline lenses over three years of follow-up; ultimately, the decision for intervention should be part of a shared decision-making process between the clinician and the patient. For people with chronic PACG and visually significant cataracts, low certainty evidence suggested that combining phacoemulsification with either viscogonioplasty or goniosynechialysis does not confer any additional benefit over phacoemulsification alone. There was insufficient evidence to draw any meaningful conclusions regarding phacoemulsification versus trabeculectomy. Low certainty evidence suggested that combining phacoemulsification with trabeculectomy does not confer any additional benefit over phacoemulsification alone, and may cause more complications instead. These conclusions only apply to short- to medium-term outcomes; studies with longer follow-up periods can help assess whether these effects persist in the long term.