Primary Practice Patterns for the Initial Management of Open Angle Glaucoma.

PRCIS: About one-fourth of survey respondents from an ASCRS database initiate treatment for primary open angle glaucoma (POAG) with laser trabeculoplasty. Factors impacting physicians' choice of laser versus topical treatment for POAG were explored. PURPOSE: To characterize primary treatment preferences (topical medication versus laser trabeculoplasty or intracameral sustained release implants) in primary open angle glaucoma (POAG) patients and determine factors related to primary intervention selection. METHODS: A 33-question survey was distributed to an American Society of Cataract and Refractive Surgery database on treatment choices made by ophthalmologists for POAG. Data collected included country of practice, years of practice, completion of glaucoma fellowship training, type of practice, and preference for the first line of treatment for POAG. Multiple logit regression was used to compare the effect of covariates on physicians' choice of either topical medication or laser trabeculoplasty for POAG. RESULTS: A total of 252 of 19,246 (1.3%) surveys were returned. Almost three-quarters of respondents used topical medication as the first line of treatment for POAG (73.6%), whereas 26.4% preferred to start with laser treatment. Significant variables associated with the selection of laser (vs. drops) are practicing in the United States (odds ratio [OR] 2.85; 95% CI, 1.33-6.10), the more recent completion of ophthalmology residency (OR 1.95; 95% CI, 1.00-3.77), the greater volume of minimally invasive glaucoma surgeries (MIGS) (OR 1.68; 95% CI, 1.18-2.40), and a glaucoma patient base greater than 25% (OR 2.21; 95% CI, 1.09-4.48). CONCLUSIONS: For the first-line treatment of POAG, laser trabeculoplasty is more likely to be preferred, over topical drops, by U.S. physicians who are relatively new in practice, who have a larger glaucoma patient base, and who perform more MIGS.

The Evolving Surgical Paradigm of Scleral Allograft Bio-Tissue Use in Ophthalmic Surgery: Techniques and Clinical Indications for Ab-Externo and Ab-Interno Scleral Reinforcement.

To review the latest surgical advances and evolving clinical use of scleral bio-tissue for reinforcement in the eye and review the published literature on novel surgical applications of scleral allograft bio-tissue. Conventional surgical procedures for scleral reinforcement using homologous scleral allograft have been traditionally ab-externo interventions comprising of anterior or posterior reinforcement of the sclera for clinical indications such as trauma, scleromalacia, glaucoma drainage device coverage, scleral perforation, buckle repair as well as posterior reinforcement for pathologic myopia and staphyloma. There have been a few novel ab-interno uses of scleral bio-tissue for reinforcement in both retina and glaucoma. Over the last decade, there has been an increase in peer-reviewed publications on scleral reinforcement, reflecting more interest in its clinical applications. With favorable biological and biomechanical properties, scleral allograft may be an ideal substrate for an array of new applications and surgical uses.

The normalizing effects of the CYP46A1 activator efavirenz on retinal sterol levels and risk factors for glaucoma in Apoj-/- mice.

Apolipoprotein J (APOJ) is a multifunctional protein with genetic evidence suggesting an association between APOJ polymorphisms and Alzheimer's disease as well as exfoliation glaucoma. Herein we conducted ocular characterizations of Apoj-/- mice and found that their retinal cholesterol levels were decreased and that this genotype had several risk factors for glaucoma: increased intraocular pressure and cup-to-disk ratio and impaired retinal ganglion cell (RGC) function. The latter was not due to RGC degeneration or activation of retinal Muller cells and microglia/macrophages. There was also a decrease in retinal levels of 24-hydroxycholesterol, a suggested neuroprotectant under glaucomatous conditions and a positive allosteric modulator of N-methyl-D-aspartate receptors mediating the light-evoked response of the RGC. Therefore, Apoj-/- mice were treated with low-dose efavirenz, an allosteric activator of CYP46A1 which converts cholesterol into 24-hydroxycholesterol. Efavirenz treatment increased retinal cholesterol and 24-hydroxycholesterol levels, normalized intraocular pressure and cup-to-disk ratio, and rescued in part RGC function. Retinal expression of Abcg1 (a cholesterol efflux transporter), Apoa1 (a constituent of lipoprotein particles), and Scarb1 (a lipoprotein particle receptor) was increased in EVF-treated Apoj-/- mice, indicating increased retinal cholesterol transport on lipoprotein particles. Ocular characterizations of Cyp46a1-/- mice supported the beneficial efavirenz treatment effects via CYP46A1 activation. The data obtained demonstrate an important APOJ role in retinal cholesterol homeostasis and link this apolipoprotein to the glaucoma risk factors and retinal 24-hydroxycholesterol production by CYP46A1. As the CYP46A1 activator efavirenz is an FDA-approved anti-HIV drug, our studies suggest a new therapeutic approach for treatment of glaucomatous conditions.

α-Synuclein modulates fibronectin expression in the trabecular meshwork independent of TGFß2.

α-Synuclein (α-Syn) is implicated in Parkinson's disease (PD), a neuromotor disorder with prominent visual symptoms. The underlying cause of motor dysfunction has been studied extensively, and is attributed to the death of dopaminergic neurons mediated in part by intracellular aggregation of α-Syn. The cause of visual symptoms, however, is less clear. Neuroretinal degeneration due to the presence of aggregated α-Syn has been reported, but the evidence is controversial. Other symptoms including those arising from primary open angle glaucoma (POAG) are believed to be the side-effects of medications prescribed for PD. Here, we explored the alternative hypothesis that dysfunction of α-Syn in the anterior eye alters the interaction between the actin cytoskeleton of trabecular meshwork (TM) cells with the extracellular matrix (ECM), impairing their ability to respond to physiological changes in intraocular pressure (IOP). A similar dysfunction in neurons is responsible for impaired neuritogenesis, a characteristic feature of PD. Using cadaveric human and bovine TM tissue and primary human TM cells as models, we report two main observations: 1) α-Syn is expressed in human and bovine TM cells, and significant amounts of monomeric and oligomeric α-Syn are present in the AH, and 2) primary human TM cells and human and bovine TM tissue endocytose extracellular recombinant monomeric and oligomeric α-Syn via the prion protein (PrPC), and upregulate fibronectin (FN) and α-smooth muscle actin (α-SMA), fibrogenic proteins implicated in POAG. Transforming growth factor ß2 (TGFß2), a fibrogenic cytokine implicated in ∼50% cases of POAG, is also increased, and so is RhoA-associated coiled-coil-containing protein kinase 1 (ROCK-1). However, silencing of α-Syn in primary human TM cells reduces FN, α-SMA, and ROCK-1 in the absence or presence of over-expressed active TGFß2, suggesting modulation of FN and ROCK-1 independent of, or upstream of TGFß2. These observations suggest that extracellular α-Syn modulates ECM proteins in the TM independently or via PrPC by activating the RhoA-ROCK pathway. These observations reveal a novel function of α-Syn in the anterior eye, and offer new therapeutic options.

Effect of SPARC Suppression in Mice, Perfused Human Anterior Segments, and Trabecular Meshwork Cells.

Purpose: Secreted protein, acidic and rich in cysteine (SPARC) elevates intraocular pressure (IOP), increases certain structural extracellular matrix (ECM) proteins in the juxtacanalicular trabecular meshwork (JCT), and decreases matrix metalloproteinase (MMP) protein levels in trabecular meshwork (TM) endothelial cells. We investigated SPARC as a potential target for lowering IOP. We hypothesized that suppressing SPARC will decrease IOP, decrease structural JCT ECM proteins, and alter the levels of MMPs and/or their inhibitors. Methods: A lentivirus containing short hairpin RNA of human SPARC suppressed SPARC in mouse eyes and perfused cadaveric human anterior segments with subsequent IOP measurements. Immunohistochemistry determined structural correlates. Human TM cell cultures were treated with SPARC suppressing lentivirus. Quantitative reverse transcriptase polymerase chain reaction (PCR), immunoblotting, and zymography determined total RNA, relative protein levels, and MMP enzymatic activity, respectively. Results: Suppressing SPARC decreased IOP in mouse eyes and perfused human anterior segments by approximately 20%. Histologically, this correlated to a decrease in collagen I, IV, and VI in both the mouse TM and human JCT regions; in the mouse, fibronectin was also decreased but not in the human. In TM cells, collagen I and IV, fibronectin, MMP-2, and tissue inhibitor of MMP-1 were decreased. Messenger RNA of the aforementioned genes was not changed. Plasminogen activator inhibitor 1 (PAI-1) was upregulated in vitro by quantitative PCR and immunoblotting. MMP-1 activity was reduced in vitro by zymography. Conclusions: Suppressing SPARC decreased IOP in mice and perfused cadaveric human anterior segments corresponding to qualitative structural changes in the JCT ECM, which do not appear to be the result of transcription regulation.

The role of trabeculectomy in the era of minimally invasive glaucoma surgery.

PURPOSE OF REVIEW: This review discusses recent findings in surgical management of glaucoma, focusing on trabeculectomy and minimally invasive glaucoma surgery (MIGS). We discuss how the role these procedures play in conjunction with phacoemulsification. RECENT FINDINGS: New findings of the Primary Trab Vs Tube study and findings regarding the Hydrus, Xen 45, Kahook dual blade, Ab-interno Canaloplasty and head-to-head MIGS studies are summarized. SUMMARY: Patients with glaucoma greatly benefit from combining cataract surgery with a MIGS procedure that can be tailored to disease severity and medication use. Certain MIGS combined with phacoemulsification in severe and refractory glaucoma can potentially delay incisional glaucoma, although trabeculectomy- mitomycin C (MMC) still remains the best option in certain patient populations. We provide an update in the MIGS treatment paradigm based on newer, stronger evidence.

Antibiotic prophylaxis of postoperative endophthalmitis after cataract surgery: results of the 2021 ASCRS member survey.

In an online survey of >1200 global cataract surgeons, 66% were using intracameral (IC) antibiotic prophylaxis. This compared with 50% and 30% in the 2014 and 2007 surveys, respectively. Irrigation bottle infusion and intravitreal injection was each used by only 5% of respondents. For IC antibiotics, vancomycin was used by 6% in the United States (52% in 2014), compared with 83% for moxifloxacin (31% in 2014). Equal numbers used compounded moxifloxacin or the Vigamox bottle as the source. There was a decrease in respondents using preoperative (73% from 85%) and postoperative (86% from 97%) topical antibiotic prophylaxis; the latter was not used by 24% of surgeons injecting IC antibiotics. Reasons cited by those not using IC antibiotics include mixing/compounding risk (66%) and being unconvinced of the need (48%). However, 80% believe having a commercially approved IC antibiotic is important; if reasonably priced, this would increase adoption of IC prophylaxis to 93%.

Three-Year Findings of the HORIZON Trial: A Schlemm Canal Microstent for Pressure Reduction in Primary Open-Angle Glaucoma and Cataract.

PURPOSE: To report 3-year outcomes of the HORIZON study comparing cataract surgery (CS) with Hydrus Microstent (Ivantis, Inc) implantation versus CS alone. DESIGN: Multicenter randomized clinical trial. PARTICIPANTS: Five hundred fifty-six eyes from 556 patients with cataract and primary open-angle glaucoma (POAG) treated with 1 or more glaucoma medication, washed out diurnal intraocular pressure (IOP) of 22 to 34 mmHg, and no prior incisional glaucoma surgery. METHODS: After phacoemulsification, eyes were randomized 2:1 to receive a Hydrus Microstent or no stent. Follow-up included comprehensive eye examinations through 3 years. MAIN OUTCOME MEASURES: Outcome measures included IOP, medical therapy, reoperation rates, visual acuity, adverse events, and changes in corneal endothelial cell counts. RESULTS: Three hundred sixty-nine eyes were randomized to microstent treatment and 187 to CS only. Preoperative IOP, medication use, washed-out diurnal IOP, and glaucoma severity did not differ between the two treatment groups. At 3 years, IOP was 16.7 ± 3.1 mmHg in the microstent group and 17.0 ± 3.4 mmHg in the CS group (P = 0.85). The number of glaucoma medications was 0.4 ± 0.8 in the microstent group and 0.8 ± 1.0 in the CS group (P < 0.001), and 73% of microstent group eyes were medication free compared with 48% in the CS group (P < 0.001). The microstent group included a higher proportion of eyes with IOP of 18 mmHg or less without medications compared with the CS group (56.2% vs. 34.6%; P < 0.001), as well as IOP reduction of at least 20%, 30%, or 40% compared with CS alone. The cumulative probability of incisional glaucoma surgery was lower in the microstent group (0.6% vs. 3.9%; hazard ratio, 0.156; 95% confidence interval, 0.031-0.773; P = 0.020). No difference was found in postoperative corneal endothelial cell loss between groups. No procedure- or device-related serious adverse events resulting in vision loss occurred in either group. CONCLUSIONS: Combined CS and microstent placement for mild to moderate POAG is safe, more effective in lowering IOP with fewer medications, and less likely to result in further incisional glaucoma filtration surgery than CS alone at 3 years.

Secreted protein acidic and rich in cysteine (SPARC) knockout mice have greater outflow facility.

PURPOSE: Secreted protein acidic and rich in cysteine (SPARC) is a matricellular protein that regulates intraocular pressure (IOP) by altering extracellular matrix (ECM) homeostasis within the trabecular meshwork (TM). We hypothesized that the lower IOP previously observed in SPARC -/- mice is due to a greater outflow facility. METHODS: Mouse outflow facility (Clive) was determined by multiple flow rate infusion, and episcleral venous pressure (Pe) was estimated by manometry. The animals were then euthanized, eliminating aqueous formation rate (Fin) and Pe. The C value was determined again (Cdead) while Fin was reduced to zero. Additional mice were euthanized for immunohistochemistry to analyze ECM components of the TM. RESULTS: The Clive and Cdead of SPARC -/- mice were 0.014 ± 0.002 µL/min/mmHg and 0.015 ± 0.002 µL/min/mmHg, respectively (p = 0.376, N/S). Compared to the Clive = 0.010 ± 0.002 µL/min/mmHg and Cdead = 0.011 ± 0.002 µL/min/mmHg in the WT mice (p = 0.548, N/S), the Clive and Cdead values for the SPARC -/- mice were higher. Pe values were estimated to be 8.0 ± 0.2 mmHg and 8.3 ± 0.7 mmHg in SPARC -/- and WT mice, respectively (p = 0.304, N/S). Uveoscleral outflow (Fu) was 0.019 ± 0.007 µL/min and 0.022 ± 0.006 µL/min for SPARC -/- and WT mice, respectively (p = 0.561, N/S). Fin was 0.114 ± 0.002 µL/min and 0.120 ± 0.016 µL/min for SPARC -/- and WT mice (p = 0.591, N/S). Immunohistochemistry demonstrated decreases of collagen types IV and VI, fibronectin, laminin, PAI-1, and tenascin-C within the TM of SPARC -/- mice (p < 0.05). CONCLUSIONS: The lower IOP of SPARC -/- mice is due to greater aqueous humor outflow facility through the conventional pathway. Corresponding changes in several matricellular proteins and ECM structural components were noted in the TM of SPARC -/- mice.

Outflow Facility Effects of 3 Schlemm's Canal Microinvasive Glaucoma Surgery Devices.

PURPOSE: To study the effect of 3 Schlemm's canal (SC) microinvasive glaucoma surgery (MIGS) devices on outflow facility. DESIGN: Paired comparisons, randomized design, baseline-controlled study. PARTICIPANTS: Thirty-six pairs of dissected anterior segments from donated human eye bank eyes without glaucoma were studied. A baseline measurement was collected from each eye to serve as its control. METHODS: Using a constant pressure perfusion method, outflow facility was measured in paired eyes from human donors. Measurements were made at perfusion pressures of 10 mmHg, 20 mmHg, 30 mmHg, and 40 mmHg. Outflow facility was measured before (baseline control) and after the implantation of an SC glaucoma drainage device or sham procedure. Three sets of experiments were carried out comparing 1 and 2 iStent Trabecular Micro-Bypass Stents and 2 iStent Inject implants with the Hydrus Microstent. MAIN OUTCOME MEASURES: Change in outflow facility from baseline or contralateral eye. RESULTS: After Hydrus placement, the outflow facility increased from 0.23±0.03 µl/minute per millimeter of mercury at baseline to 0.38±0.03 µl/minute per millimeter of mercury (P < 0.001). The percent increase in outflow facility was 79±21% for the Hydrus and 11±16% for the 2 iStent Inject devices, a difference that was significant (P = 0.018). Outflow facility with 1 iStent (0.38±0.07 µl/minute per millimeter of mercury) was greater than baseline (0.28±0.03 µl/minute per millimeter of mercury; P = 0.031). The 1 iStent showed a greater increase in outflow facility from baseline (0.10±0.04 µl/minute per millimeter of mercury) compared with the sham procedure (-0.08±0.05 µl/minute per millimeter of mercury; P = 0.042). No other significant differences were found. CONCLUSIONS: The longer the MIGS device, and thus the more SC that it dilates, the greater the outflow facility.

TGFß2-Hepcidin Feed-Forward Loop in the Trabecular Meshwork Implicates Iron in Glaucomatous Pathology.

Purpose: Elevated levels of transforming-growth-factor (TGF)-ß2 in the trabecular meshwork (TM) and aqueous humor are associated with primary open-angle glaucoma (POAG). The underlying mechanism includes alteration of extracellular matrix homeostasis through Smad-dependent and independent signaling. Smad4, an essential co-Smad, upregulates hepcidin, the master regulator of iron homeostasis. Here, we explored whether TGF-ß2 upregulates hepcidin, implicating iron in the pathogenesis of POAG. Methods: Primary human TM cells and human and bovine ex vivo anterior segment organ cultures were exposed to bioactive TGF-ß2, hepcidin, heparin (a hepcidin antagonist), or N-acetyl carnosine (an antioxidant), and the change in the expression of hepcidin, ferroportin, ferritin, and TGF-ß2 was evaluated by semiquantitative RT-PCR, Western blotting, and immunohistochemistry. Increase in reactive oxygen species (ROS) was quantified with dihydroethidium, an ROS-sensitive dye. Results: Primary human TM cells and bovine TM tissue synthesize hepcidin locally, which is upregulated by bioactive TGF-ß2. Hepcidin downregulates ferroportin, its downstream target, increasing ferritin and iron-catalyzed ROS. This causes reciprocal upregulation of TGF-ß2 at the transcriptional and translational levels. Heparin downregulates hepcidin, and reduces TGF-ß2-mediated increase in ferritin and ROS. Notably, both heparin and N-acetyl carnosine reduce TGF-ß2-mediated reciprocal upregulation of TGF-ß2. Conclusions: The above observations suggest that TGF-ß2 and hepcidin form a self-sustained feed-forward loop through iron-catalyzed ROS. This loop is partially disrupted by a hepcidin antagonist and an anti-oxidant, implicating iron and ROS in TGF-ß2-mediated POAG. We propose that modification of currently available hepcidin antagonists for ocular use may prove beneficial for the therapeutic management of TGF-ß2-associated POAG.

Comparative corneal endothelial cell toxicity of differing intracameral moxifloxacin doses after phacoemulsification.

PURPOSE: To determine whether intracameral moxifloxacin 500 µg is noninferior to 250 µg for central endothelial cell loss (ECL) after phacoemulsification. SETTING: Aravind Eye Care System. DESIGN: Prospective masked randomized study. METHODS: Eyes with bilateral nuclear cataracts, central endothelial cell density (ECD) of more than 2000 cells/mm, and ECD not differing between eyes by more than 200 cells/mm underwent phacoemulsification at least 14 days apart. Intraoperatively, the first eye was randomized to receive either a 500 or 250 µg dose of moxifloxacin intracamerally and received the other dose for the second-eye surgery. Postoperative course was monitored at 1 day, 1 week, 1 month, and 3 months. Preoperative and 30-day and 90-day postoperative central ECD was determined by a reading center for a masked analysis of ECL at 3 months postoperatively. RESULTS: Fifty eyes of 25 patients (aged 48 to 69 years) underwent uneventful surgery and had normal postoperative courses. The point estimate (PE) and 95% CI for the mean difference in % ECL between the 500 µg and 250 µg doses at 3 months postoperatively was 0.8% (-5.8%, 7.4%). Upon identifying and removing 2 outliers, noninferiority was proven with a mean difference of the PE, -2.2% (CI, -6.5%, 2.1%). CONCLUSIONS: Clinical and corneal endothelial cell were comparable in this study population for the 250 µg and 500 µg doses of intracameral moxifloxacin. Both doses were well tolerated clinically, supporting the use of the higher dose for improved antimicrobial coverage for the prevention of postoperative endophthalmitis.

A Prospective Randomized Trial Comparing Hydrus and iStent Microinvasive Glaucoma Surgery Implants for Standalone Treatment of Open-Angle Glaucoma: The COMPARE Study.

PURPOSE: To compare the efficacy of different microinvasive glaucoma surgery (MIGS) devices for reducing intraocular pressure (IOP) and medications in open-angle glaucoma (OAG). DESIGN: Prospective, multicenter, randomized clinical trial. PARTICIPANTS: One hundred fifty-two eyes from 152 patients aged 45 to 84 years with OAG, Shaffer angle grade III-IV, best-corrected visual acuity (BCVA) 20/30 or better, and IOP 23 to 39 mmHg after washout of all hypotensive medications. Eyes with secondary glaucoma other than pseudoexfoliative or pigmentary glaucoma, angle closure, previous incisional glaucoma surgery, or any significant ocular pathology other than glaucoma were excluded. INTERVENTION: Study eyes were randomized 1:1 to standalone MIGS consisting of either 1 Hydrus Microstent (Ivantis, Inc, Irvine, CA) or 2 iStent Trabecular Micro Bypass devices (Glaukos Inc, San Clemente, CA). Follow-up was performed 1 day, 1 week, and 1, 3, 6, and 12 months postoperatively. MAIN OUTCOME MEASURES: Within-group and between-group differences in IOP and medications at 12 months and complete surgical success defined as freedom from repeat glaucoma surgery, IOP 18 mmHg or less, and no glaucoma medications. Safety measures included the frequency of surgical complications, changes in visual acuity, slit-lamp findings, and adverse events. RESULTS: Study groups were well matched for baseline demographics, glaucoma status, medication use, and baseline IOP. Twelve-month follow-up was completed in 148 of 152 randomized subjects (97.3%). At 12 months, the Hydrus had a greater rate of complete surgical success (P < 0.001) and reduced medication use (difference = -0.6 medications, P = 0.004). More Hydrus subjects were medication free at 12 months (difference = 22.6% P = 0.0057). Secondary glaucoma surgery was performed in 2 eyes in the 2-iStent group (3.9%) and in none of the Hydrus eyes. Two eyes in the Hydrus group and 1 in the 2-iStent group had BCVA loss of ≥2 lines. CONCLUSION: Standalone MIGS in OAG with the Hydrus resulted in a higher surgical success rate and fewer medications compared with the 2-iStent procedure. The 2 MIGS devices have similar safety profiles.

Differential Efficacy of Combined Phacoemulsification and Endocyclophotocoagulation in Open-angle Glaucoma Versus Angle-closure Glaucoma.

PRéCIS:: This retrospective study found that combined phacoemulsification and endocyclophotocoagulation reduced intraocular pressure (IOP) to a greater degree in angle-closure glaucoma versus open-angle glaucoma and was effective for all stages of glaucoma. PURPOSE: Endocyclophotocoagulation (ECP) laser treatment of the ciliary processes is believed to decrease 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: A Retrospective chart review of eyes that underwent phaco/ECP between October 2010 and December 2016 at one institution was conducted. 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 at both 1 year (6.4 vs. 2.1 mm Hg, P=0.01; 0.9 vs. 0.2 medications, P=0.04) and final follow-up (6.2 vs. 2.4 mm Hg, 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 mm Hg, respectively, P=0.18; 0.3, 0.6, 0.4 medications, P=0.58) and final follow-up (3.3, 4.8, 0.7 mm Hg, 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 with eyes with primary open-angle glaucoma. This finding could be partially or entirely due to concurrent cataract extraction and greater CACG preoperative IOP. Phaco/ECP was effective in all stages of glaucoma.

Co-management of cataract and glaucoma in the era of minimally invasive glaucoma surgery.

PURPOSE OF REVIEW: This review discusses the options available to be used in conjunction with phacoemulsification cataract surgery to control intraocular pressure. We present a strategy for planning which surgery should be performed based on goals of care. RECENT FINDINGS: New clinical evidence for using the CyPass, Kahook and Xen45 devices has been published recently and is summarized. SUMMARY: Cataract and glaucoma frequently exist together. Because the field of glaucoma surgical care is expanding and cataract surgery is becoming progressively safer, it is important to frequently re-evaluate our treatment paradigms. We review and evaluate current studies and treatment options.

Risk factors for tube exposure as a late complication of glaucoma drainage implant surgery.

PURPOSE: The purpose of this study was to evaluate the risk factors for tube exposure after glaucoma drainage implant surgery. PATIENTS AND METHODS: This was a retrospective case-controlled observational study of 64 eyes from 64 patients. Thirty-two eyes of 32 patients with tube erosion requiring surgical revision were compared with 32 matched control eyes of 32 patients. Univariate and multivariate risk factor analyses were performed. RESULTS: Mean age was significantly younger in the tube exposure group compared with the control group (48.2±28.1 years versus 67.3±18.0 years, respectively; P=0.003). The proportion of diabetic patients (12.5%) in the tube exposure group was significantly less (P=0.041) compared with the control group (37.5%). Comparisons of the type and position of the drainage implant were not significantly different between the two groups. The average time to tube exposure was 17.2±18.0 months after implantation of the drainage device. In both univariate and multivariate analyses, younger age (P=0.005 and P=0.027) and inflammation prior to tube exposure (P≤0.001 and P=0.004) were significant risk factors. Diabetes was a significant risk factor only in the univariate analysis (P=0.027). CONCLUSION: Younger age and inflammation were significant risk factors for tube exposure after drainage implant surgery.

Secreted Protein Acidic and Rich in Cysteine in Ocular Tissue.

Secreted protein acidic and rich in cysteine (SPARC), also known as osteonectin or BM-40, is the prototypical matricellular protein. Matricellular proteins are nonstructural secreted proteins that provide an integration between cells and their surrounding extracellular matrix (ECM). Regulation of the ECM is important in maintaining the physiologic function of tissues. Elevated levels of SPARC have been identified in a variety of diseases involving pathologic tissue remodeling, such as hepatic fibrosis, systemic sclerosis, and certain carcinomas. Within the eye, SPARC has been identified in the trabecular meshwork, lens, and retina. Studies have begun to show the role of SPARC in these tissues and its possible role, specifically in primary open-angle glaucoma, cataracts, and proliferative vitreoretinopathy. SPARC may, therefore, be a therapeutic target in the treatment of certain ocular diseases. Further investigation into the mechanism of action of SPARC will be necessary in the development of SPARC-targeted therapy.

Canonical wnt signaling regulates extracellular matrix expression in the trabecular meshwork.

PURPOSE: Canonical Wnt signaling has emerged as a critical regulator of aqueous outflow facility and intraocular pressure (IOP). In this study, we examine the role of canonical Wnt signaling on extracellular matrix (ECM) expression in the trabecular meshwork (TM) and explore the molecular mechanisms involved. METHODS: ß-catenin localization in human TM tissue was examined using immunofluorescent staining. Primary human TM cells were incubated with lithium chloride (LiCl) and the effect on active ß-catenin expression was assessed by immunoblot. Adenovirus expressing a dominant-negative TCF4 mutant that lacks a ß-catenin binding domain was used. Changes in the levels of the microRNA-29 (miR-29) family and ECM proteins were determined by real-time quantitative PCR and immunoblot analysis, respectively. RESULTS: ß-catenin was expressed throughout the TM, with localization primarily to the plasma membrane. Incubation of TM cells with lithium chloride increased the expression of active ß-catenin. Lithium chloride treatment upregulated miR-29b expression, and suppressed the levels of various ECM proteins under both basal and TGF-ß2 stimulatory conditions. Infection of TM cells with a dominant-negative TCF4 mutant induced ECM levels without a significant change in the expression of the miR-29 family. CONCLUSIONS: Collectively, our data identify the canonical Wnt signaling pathway as an important modulator of ECM expression in the TM and provide a mechanistic framework for its regulation of outflow facility and IOP.

Aqueous outflow: segmental and distal flow.

UNLABELLED: The elevated intraocular pressure (IOP) of primary open-angle glaucoma is caused by impaired outflow of aqueous humor through the trabecular meshwork. Within the juxtacanalicular region, alterations of both extracellular matrix homeostasis and the cellular tone of trabecular meshwork endothelial and the inner wall of Schlemm canal cells affect outflow. Newer pharmacologic agents that target trabecular meshwork and Schlemm canal cell cytoskeleton lower IOP. Aqueous drainage occurs nonhomogenously with greater flow going through certain portions of the TM and less going through other portions-a concept known as segmental flow, which is theoretically the result of outflow being dependent on the presence of discrete pores within Schlemm canal. The limited long-term success of trabecular meshwork bypass surgeries implicates the potential impact of resistance in Schlemm canal itself and collector channels. Additionally, others have observed that outflow occurs preferentially near collector channels. These distal structures may be more important to aqueous outflow than previously believed. FINANCIAL DISCLOSURE: Dr. Rhee is a consultant to Aerie Pharmaceuticals, Alcon Laboratories, Inc., Allegan, Inc., Aquesys, Inc., Glaukos Corp., Ivantis, Inc., Johnson & Johnson, Merck Sharp & Dohme Corp. and Santen, Inc., and has received research funding from Alcon Laboratories, Inc., Merck Sharp & Dohme Corp., and Ivantis, Inc. No other author has a financial or proprietary interest in any material or method mentioned.

A survey of preoperative blood tests in primary open-angle glaucoma patients versus cataract surgery patients.

PURPOSE: To investigate biomarker differences in routine preoperative blood tests performed on primary open-angle glaucoma (POAG) case and control patients presenting for anterior segment eye surgery. METHODS: POAG cases and age-related cataract surgery patients (controls) who underwent anterior segment surgery at Massachusetts Eye and Ear from January 2009 through March 2012 were identified by retrospective record review. Patients with diabetes mellitus, secondary glaucoma, and cataract due to trauma or steroid exposure were excluded. Data on demographic features, preoperative ophthalmological and medical diagnosis, blood pressure, anthropometric measures, basic metabolic panel, and complete blood count were extracted from the medical records. Univariate differences in lab values between POAG cases and controls were assessed using unpaired t tests. Multivariate logistic regression analysis was completed to determine the independent associations of biomarkers with POAG. RESULTS: A total of 150 cases and 150 age-related controls were included. In multivariate analysis, higher AG was inversely associated with POAG (odds ratio [OR] = 0.90; 95% confidence interval [CI], 0.80-1.00), and higher Cl- level was positively associated with POAG (OR = 1.15; 95% CI, 1.02-1.29). The lower AG in POAG patients could be explained by higher IgG levels as the available data in post hoc analysis showed a nonsignificant trend toward higher IgG in cases compared to controls (17 vs 23; 1142 ± 284 mg/dl vs 1028 ± 291 mg/dl; P = 0.22). Furthermore, in multivariable analysis, a higher red blood cell count was also associated with POAG (OR = 1.91; 95% CI, 1.11-3.28). CONCLUSIONS: Patients with POAG presenting for anterior segment surgery had a lower AG compared to age-related cataract surgery patients. The etiology of this reduced gap is unclear but the possible contribution of IgG warrants further exploration. The etiology of higher red blood cell counts in POAG cases is unknown and deserves further exploration.