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Stratification of phaco-trabectome surgery results using a glaucoma severity index in a retrospective analysis Pritha Roy , MD, Ralitsa T. Loewen , MD, Yalong Dang , MD, Hardik A. Parikh , BS, Nils A. Loewen *, MD, PhD 1

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1: Department of Ophthalmology, School of Medicine, University of Pittsburgh, Pittsburgh, United States of America 2: Institute of Ophthalmology and Visual Science, Rutgers, New Jersey Medical School, Newark, NJ, United States of America

*corresponding author: Nils A. Loewen, MD, PhD 203 Lothrop St Suite 819 Pittsburgh, PA 15213 Email: [email protected] Phone: 412-605-1541

Running Head/Abbreviated Title: Stratifying Phaco-trabectome outcomes Category: Original Article - Clinical Science Financial Support: Research to Prevent Blindness Departmental Grant. Individual Grant from Department of Ophthalmology, University of Pittsburgh. Alpha Omega Alpha Carolyn L. Kuckein Medical Student Research Fellowship. The sponsor or funding organization had no role in the design or conduct of this research Conflict of Interest: NAL has received honoraria from NeoMedix, Corp. for wet labs and lectures.

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Abstract Background: To stratify the outcomes of phacoemulsification combined with trabectome surgery (PT) using glaucoma severity index. Design: This is a retrospective, observational cohort study performed in the Department of Ophthalmology, University of Pittsburgh Medical Center. Participants or Samples: 498 cases with only PT and 12 months follow up were analyzed. These glaucoma patients had visually significant cataract and the need to lower IOP or the number of glaucoma medications. Methods: All eyes underwent trabectome first followed by phacoemulsification and lens implantation. Main Outcome Measures: GI incorporated preoperative IOP, medications and visual field. Linear regression was used to detect the association between GI group and IOP reduction at one year. Log-rank was used for survival analysis. Results: Mean IOP reduction after one year was 2.9±4.4, 3.6±5.0, 3.9±5.3, and 9.2±7.6 mmHg for GI groups 1 to 4, respectively. Linear regression showed patients in a higher GI group had an IOP reduction greater by 1.7±0.2 mmHg than patients in a lower GI group. Survival rate at 12 months was 98%, 93%, 96% and 88% for GI groups 1 to 4 (P<0.05). Conclusions: A substantial IOP reduction was seen in subjects with more advanced glaucoma suggesting that the trabecular meshwork is the primary impediment to outflow and its ablation

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benefits those eyes relatively more than in mild glaucoma. Higher GI groups are expected to have a greater reduction of IOP.

Key Words: Glaucoma, Open-angle, Trabeculectomy, Phacoemulsification, Glaucoma Incisional Surgery

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Introduction Cataract and glaucoma are the two main causes of visual impairment worldwide (1) but while vision can be recovered by cataract extraction and intraocular lens implantation, vision loss from glaucoma is irreversible. Co-existence of open-angle glaucoma and cataract are frequently seen in the elderly population. Incidence and prevalence of both increase with age (2). Elevated IOP and use of glaucoma medications can increase the risk of development of a nuclear cataract (3). Similarly, glaucoma surgery can also accelerate cataract progression (4). Removal of cataracts can confer a modest IOP reduction and have occasionally been recommended as a first intervention towards controlling pressure in glaucoma (5–7). In countries where access to more advanced and more expensive technology exists, phacoemulsification is the most frequently performed type of cataract surgery (8) and produces the better visual results (9).

Ab interno trabeculectomy (AIT) belongs to the family of microincisional glaucoma surgeries (10) that are relatively standardized and have a favorable safety profile compared to traditional filtering surgeries (11). AIT lowers IOP by ionizing and disrupting the diseased trabecular meshwork and creates a direct pathway for aqueous to exit the anterior chamber (10,12). Depending on the severity of the respective diseases and the additional requirement for lowering IOP, phacoemulsification can be combined with trabectome (PT) benefitting the patient with fewer procedures and better cost effectiveness compared to long-term use of drops or to two separate operating room procedures (13). Glaucoma can be graded according to the visual field function, optic nerve damage, or both (14–16).

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Previous data on AIT with phacoemulsification after a failed trabeculectomy suggested that eyes with more advanced glaucoma may experience a larger IOP reduction although this did not reach statistical significance (17). When trabectome surgery is performed as a single procedure to lower IOP a bigger pressure decrease can be observed (18). We recently described that the impact of phacoemulsification on IOP reduction is negligible when PT is compared to trabectome surgery in eyes that remain phakic (19). In this study, we analyzed IOP reduction from cataract surgery combined with trabectome as a function of a glaucoma index (GI). We also stratified outcomes by glaucoma severity based on preoperative IOP, number of preoperative medications, and visual field damage. We hypothesized that outcomes of PT would be similar regardless of GI.

Methods Data for this retrospective, observational cohort study was collected after approval by the Institutional Review Board of the University of Pittsburgh, in accordance with the Declaration of Helsinki and the Health Insurance Portability and Accountability Act (IRB#REN15100055). Informed consent was not required. Only cases that had undergone trabectome surgery combined with phacoemulsification were included. Exclusion criteria was follow up less than 12 months, any other surgery during this time or diagnosis of neovascular or active uveitic glaucoma. For each patient, a specific target IOP was established by the treating glaucoma specialist deemed to prevent further nerve damage. The indications for PT consisted of IOP above target with progressive glaucoma on maximally tolerated medical therapy, or stable glaucoma with the need to decrease the number of

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medications and a visually significant cataract with at least 0.4 logMAR (20/50 Snellen) visual acuity testing. AIT was completed before same session phacoemulsification in phaco-AIT (10). The visual acuity was expressed as the logarithm of the minimum angle of resolution (logMAR). Based on the most recent Humphrey visual field exam (Carl Zeiss Meditec, AG, Jena, Germany), visual fields were grouped into four categories of up to mild, up to moderate, up to advanced, and more than advanced visual field damage (20), and designated 1, 2, 3 and 4 points, respectively. All patients received a comprehensive slit lamp and ophthalmoscopy exam before surgery. Anterior chamber angles in all patients were graded by Shaffer grade (SG) (21,22), a classification system in which ‘0’ to ‘slit’ represents a totally or partially closed angle with potential for angle closure that is present or very likely, ‘1’ an angle width of 10° (very narrow) and closure potential that is probable, ‘2’ representing 20° and possible potential for closure, ‘3’ standing for 20° to 45° with unlikely closure and grade ‘4’ indicating a wide open angle and improbable potential for angle closure. GI was defined using the following variables: 1) Preoperative IOP, 2) numbers of medications used prior to surgery, 3) visual field status. Visual field was separated into four categories: mild, moderate, advanced and end stage where mild was assigned 1 point, moderate with 2, advanced with 3 and end stage with 4. Preoperative number of medications were divided into 4 categories: 0-1, 2, 3 or 4+, and assigned with a value of 1 to 4, respectively. Baseline IOP was divided into 3 categories: <20 mmHg, 20-29 mmHg, and greater than 30 mmHg and assigned with 1 to 3 points respectively. These categories were chosen based on IOP distribution and designed not to underrate low pressure glaucoma and to include the small number of eyes with a baseline IOP above 40. GI was then defined as preoperative IOP ⨉ preoperative number of

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medications ⨉ VF. GI was separated into 4 groups: <3 (group 1), 3-5 (group 2), 6-11 (group 3) and >12 (group 4). Linear regression was used to determine if there was an association between GI group and IOP reduction after one year. Baseline characteristics were compared by the Kruskal-Wallis and chi square tests for continuous and categorical variables between GI groups, respectively. Univariate linear regression was performed first and those variables that were found to be statistically significant were included into multivariate regression. Success was defined as IOP≤21 mmHg, at least 20% IOP reduction from baseline in any two consecutive visits after three months, and no secondary glaucoma surgery. Log-rank test was used to compare survival distributions of GI groups. Continuous data was reported as mean ± standard deviation.

Results Of 1374 patients, a total of 498 cases of phaco-AIT were included in the study after applying the exclusion criteria. The average age of the patients was 73±10 years. The average preoperative IOP was 20.6±6.6 mmHg and the average number of preoperative medications used was 2.4±1.1. The percentage of cases with mild, moderate and advanced visual field status were 33%, 33%, 34% respectively. The demographics table does not show any significant differences in age among the GI groups (Table 1). The patient distribution across GI groups was relatively even and only reached a significant difference in visual acuity and cup disc ratio (Table 1). Most patients were Caucasian, followed by Asians, and then by African Americans and Hispanics. Amongst the GI groups, the majority of

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the patients had the diagnosis of primary open angle glaucoma with Shaffer grade above 2 followed by pseudoexfoliative glaucoma. Pigmentary and steroid induced glaucoma were amongst the least common diagnosis. PEX and steroid induced glaucoma patients had a greater IOP reduction by 3.75±0.79, 4.27±1.25 mmHg than OAG patients. The cup to disc (C/D) ratio increased significantly from a mean of 0.66 to 0.81 from GI1 to GI4. In contrast, visual acuity showed a significant decrease from GI1 to GI4 with GI4 nearly half of that of GI1. At the end of 12 months, visual acuity showed a significant improvement for all the GI groups (Table 2). Most patients had a preoperative IOP below 20 mmHg and most of them used three drops to achieve that (Figure 1). The visual field damage was relatively evenly distributed among mild, moderate and advanced damage. There were no patients with end stage visual fields (Figure 1). At one year, glaucoma index groups 1 through 3 had an IOP reduction of about 4 mmHg in average while group 4, with the most advanced glaucomas, had a reduction near 10 mmHg (Figure 2). Univariate linear regression (Table 3), which was performed first, identified age, diagnosis of pigmentary glaucoma and steroid induced glaucoma, and visual acuity to be most significant. These variables were then included in the multivariate regression. In the multivariate regression analysis (Table 4), GI group, the diagnosis of pseudoexfoliation glaucoma and steroid induced glaucoma, were found to be significantly associated with IOP reduction. We examined the glaucoma index variables and their individual relationships to

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postoperative IOPs at the different time points. Patients in a higher glaucoma index group had a larger absolute IOP decrease (Figure 3). While there was an overall decrease in the number of medications in all glaucoma index groups (GI), GI3 and GI4 showed the most significant changes (p<0.05) after 6 months postoperatively (Figure 4). Individuals with more advanced visual field damage had the largest IOP reduction (Figure 5). Kaplan-Meier survival rate at 12 months was 98%, 93%, 96% and 88% for GI group 1 to 4. Log-rank test suggested a significant difference in survival distributions between GI groups. Patients in lower GI groups had a higher survival rate than those in the highest GI group (Figure 6).

Discussion In this study, we stratified the outcomes of PT by a glaucoma index and found that there is a modest correlation to the severity of open angle glaucoma indicating that a larger IOP reduction is achieved in more severe glaucoma. Phacoemulsification on its own can produce a small but significant pressure drop by 1.5 to 3 mmHg and eyes with higher preoperative IOP often a greater reduction (23,24). This effect may be the result of a trabeculoplasty-like effect (25,26), brought on by a stress response (27) or at other times due to a resolved phacomorphic component (28). On the other hand, it is not uncommon for glaucoma patients who already have a compromised trabecular meshwork to experience pressure spikes after cataract surgery (29,30); those can be prevented by combining trabecular ablation with cataract surgery (31). Combining phacoemulsification with AIT has many advantages that include functional vision improvement, reduction of cost and efforts and good safety (11).

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In the case of pseudoexfoliation, removing the cataractous lens also reduces production of pseudoexfoliation material (32) that may produce obstruction of the collector openings. It is for these reasons that patients examined here have a fundamentally different indication compared to patients who undergo trabectome surgery for the sole purpose of IOP reduction (18). It is therefore not surprising that the regression analysis in the current study only agrees with our prior study on secondary, steroid induced glaucoma and age as significantly correlated. The average age of the patients displayed the increased incidence of cataract with advancing age (1) which is also a risk factor for glaucoma (33). The percentage of patients with cataract were equally distributed amongst the different GI groups. Pseudoexfoliation can cause both earlier and more severe cataracts and may also lead to glaucoma. Pseudoexfoliation was significant in the present multivariate analysis but not in the prior, trabectome-only, study (18). Pseudoexfoliation glaucoma is often more aggressive than primary open angle glaucoma and experiences a more profound IOP reduction (34). It is therefore fitting that such patients were found more commonly in the higher GI group and had greater reduction of IOP following phacotrabectome. Interestingly, pigment dispersion glaucoma is also seen to be significantly correlated here but not in the prior trabectome-only study. The reason for this observation is most likely that such patients often have a reverse pupillary block and friction between ciliary processes, the posterior iris and the crystalline lens and may undergo cataract surgery (35) sooner than other patients. Outcomes of trabectome surgery in pigment dispersion syndrome are otherwise relatively similar to outcomes in primary open angle glaucoma (36).

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We found that patients in a GI group higher had an IOP reduction that was better by 1.69±0.24 mmHg. As could be expected, this is less than the 2.98±0.28 mmHg in trabectome-only patients (18). There was an overall decrease in the number of medications in all the groups but GI3 and GI4 showed the largest change at 12 months. We had previously applied a vigorous statistical matching method, Coarsened Exact Matching, which makes up for the shortcomings of nonrandomized studies and found that the impact of cataract surgery on IOP reduction in combination with cataract surgery is negligible (19). The results here are consistent with this and indicate that, contrary to common believe, cataract removal does not confer any additional IOP reduction in ab interno trabeculectomy.

Conclusions In conclusion, PT had a mixed indication of a visually significant cataract and the need to lower IOP or an interest in reducing the number of glaucoma medications. Despite a less absolute indication to lower IOP, a substantial pressure reduction was seen in patients with more advanced glaucoma which suggests that the trabecular meshwork is the primary impediment to outflow. Its ablation benefits eyes with more challenging glaucoma relatively more than those with mild disease. Although patients with advanced glaucoma had a slightly lower success rate, phacotrabectome does appear to make for a reasonable first line of treatment and is recommendable over phacoemulsification alone for visually significant cataracts.

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Acknowledgements The authors would like to acknowledge Jane Lin for analyzing data and applying statistical methods. This work was supported by grants from the Research to Prevent Blindness Departmental Grant, an individual grant from the Department of Ophthalmology at the University of Pittsburgh, and the Alpha Omega Alpha Carolyn L. Kuckein Medical Student Research Fellowship.

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Factors Associated with Successful Outcomes in Trabectome Only Surgery. Invest Ophthalmol Vis Sci. 2014;55(13):3174-3174. Kola S, Lagouros E, Kaplowitz K, Davis R, Schuman JS, Loewen NA. Comparison of Trabectome Ab Interno Trabeculectomy to Baerveldt and Ahmed Glaucoma Implants. Invest Ophthalmol Vis Sci. 2014;55(13):3179-3179. Tan O, Zhang X, Loewen N, et al. The Effect of Image Quality on the Reliability of Nerve Fiber Layer Measurements with Fourier-Domain OCT. Invest Ophthalmol Vis Sci. 2013;54(15):4820-4820. Legarreta JE, Conner IP, Loewen NA, Miller KV, Wingard J. The Utility of iPhone-based Imaging for Tele-ophthalmology in a Triage Capacity for Emergency Room Consultations. Invest Ophthalmol Vis Sci. 2014;55(13):4876-4876. Zhang X, Francis BA, Tan O, et al. Longitudinal and Cross-Sectional Analyses of Age and Intraocular Pressure Effects on Retinal Nerve Fiber Layer and Ganglion Cell Complex Thickness. Invest Ophthalmol Vis Sci. 2015;56(7):4574-4574. 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Gene Transfer: Delivery and Expression of DNA and RNA : A Laboratory Manual. CSHL Press; 2007:57-73. Loewen N. Ophthalmic Surgical Procedures. J Glaucoma. October 2009. doi:10.1097/IJG.0b013e3181b6e7bd. Sigler EJ, Mascarenhas KG, Tsai JC, Loewen NA. Clinicopathologic correlation of disc and peripapillary region using SD-OCT. Optom Vis Sci. 2013;90(1):84-93. Loewen R, Sengupta P, Cohen-Karni D, et al. Trabecular Meshwork Engineering and Live Tracking in Perfused Porcine Anterior Segments. In: Association for Research in Vision and Ophthalmology 2015. ; 2015. Feng L, Li W, Loewen N, Pinto HL, Hernandez MR. Laser Induced Ocular Hypertension in Mice. April 2008. J Glaucoma. http://www.ncbi.nlm.nih.gov/pubmed/26325273. Bussel II, Kaplowitz K, Schuman JS, Loewen NA, Trabectome Study Group. Outcomes of ab interno trabeculectomy with the trabectome by degree of angle opening. Br J Ophthalmol. 2015;99(7):914-919. Lewis KA, Bakkum-Gamez J, Loewen R, French AJ, Thibodeau SN, Cliby WA. Mutations in the ataxia telangiectasia and rad3-related-checkpoint kinase 1 DNA damage response axis in colon cancers. Genes Chromosomes Cancer. 2007;46(12):1061-1068. Kaplowitz, K., Wang, S., Bilonick, R., Oatts, J.T., Grippo, T., Loewen, N.A. Randomized Controlled Comparison of Titanium-Sapphire versus Standard Q-switched Nd:YAG Laser Trabeculoplasty. J Glaucoma. December 2014. Loewen, N.A., Francis, B.A., Hong, B., Dustin L., Kinast R., Bacharach, J., Radhakrishnan, S., Iwach, A., Rudavska, L., Ichhpujani, P., Katz, L.J. Repeatability of Selective Laser Trabeculoplasty (SLT) for Open Angle Glaucoma. J Ophthalmology. November 2014. Dowdy SC, Loewen RT, Aletti G, Feitoza SS, Cliby W. Assessment of outcomes and morbidity following diaphragmatic peritonectomy for women with ovarian carcinoma. Gynecol Oncol. 2008;109(2):303-307. Lewis KA, Mullany S, Thomas B, et al. Heterozygous ATR mutations in mismatch repair-deficient cancer cells have functional significance. Cancer Res. 2005;65(16):7091-7095. Loewen R, Lagouros E, Loewen NA. Trabectome-Mediated Ab Interno Trabeculectomy in Highly Complex Glaucomas. May 2014. Minckler D, Mosaed S, Francis B, Loewen N, Weinreb RN. Clinical results of ab interno trabeculotomy using the Trabectome for open-angle glaucoma: the mayo clinic series in Rochester, Minnesota. Am J Ophthalmol. 2014;157(6):1325-1326. Zhang Z, Dhaliwal AS, Tseng H, et al. Outflow tract ablation using a conditionally cytotoxic feline immunodeficiency viral vector. Invest Ophthalmol Vis Sci. 2014;55(2):935-940. Kaplowitz K, Abazari A, Honkanen R, Loewen N. iStent surgery as an option for mild to moderate glaucoma. Expert Rev Ophthalmol. 2014;9(1):11-16. Sigler EJ, Mascarenhas KG, Tsai JC, Loewen NA. Clinicopathologic Correlation of Disc and Peripapillary Region Using Spectral Domain Optical Coherence Tomography. Optom Vis Sci. 2012;90:00Y00. Kaplowitz K, Loewen NA. Minimally Invasive Glaucoma Surgery: Trabeculectomy Ab Interno. 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Preservation of aqueous outflow facility after second-generation FIV vector-mediated expression of marker genes in anterior segments of human eyes. Invest Ophthalmol Vis Sci. 2002;43(12):3686-3690. Loewen N, Barraza R, Whitwam T, Saenz DT, Kemler I, Poeschla EM. FIV Vectors. Methods Mol Biol. 2003;229:251-271. Loewen N, Chen J, Dudley VJ, Sarthy VP, Mathura JR Jr. Genomic response of hypoxic Müller cells involves the very low density lipoprotein receptor as part of an angiogenic network. Exp Eye Res. 2009;88(5):928-937. Loewen N, Fautsch MP, Peretz M, et al. Genetic modification of human trabecular meshwork with lentiviral vectors. Hum Gene Ther. 2001;12(17):2109-2119. Loewen N, Fautsch MP, Teo W-L, Bahler CK, Johnson DH, Poeschla EM. Long-term, targeted genetic modification of the aqueous humor outflow tract coupled with noninvasive imaging of gene expression in vivo. Invest Ophthalmol Vis Sci. 2004;45(9):3091-3098. Loewen N, Leske DA, Cameron JD, et al. 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Bilateral irreversible severe vision loss from cosmetic iris implants. Am J Ophthalmol. 2011;151(5):872-875.e1. Ezzat M-K, Howell KG, Bahler CK, et al. Characterization of monoclonal antibodies against the glaucoma-associated protein myocilin. Exp Eye Res. 2008;87(4):376-384. Guedes G, Tsai JC, Loewen NA. Glaucoma and aging. Curr Aging Sci. 2011;4(2):110-117. Loewen N, Barry JC. The use of cycloplegic agents. Results of a 1999 survey of German-speaking centers for pediatric ophthalmology and strabology. Strabismus. 2000;8(2):91-99. Loewen NA, Liu JHK, Weinreb RN. Increased 24-hour variation of human intraocular pressure with short axial length. Invest Ophthalmol Vis Sci. 2010;51(2):933-937. Loewen NA. Vision Loss after Trabeculectomy in Advanced Glaucoma. Glaucoma Today. 2009;(November). Loewen NA, Tanna AP. Role of Intraocular Pressure in the Diagnosis and Treatment of Glaucoma. In: Schacknow PN, Samples JR, eds. Springer; 2010:1016. Loewen N, Tsai JC. 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Figure legends Figure 1. Distribution of glaucoma index variables. Most patients had a preoperative intraocular pressure in the range below 20 mmHg. Three medications was the most common median number of eye drops used. Visual field score distribution was even and included a relatively large number of eyes with advanced visual field damage. †

IOP: Intraocular pressure

Figure 2. IOP reduction at one year by glaucoma index group. The largest IOP reduction was observed in GI 4 with more severe glaucoma. †

GI = Glaucoma Index, ‡IOP: Intraocular pressure

Figure 3. Individual IOPs by glaucoma index group. Patients in a higher glaucoma index (GI) group had a larger absolute reduction of IOP (table: mean±SD). †

GI = Glaucoma Index, ‡IOP: Intraocular pressure, §D: Day, ¶M: Month

Figure 4. Mean number of medications by glaucoma index group. While there was an overall decrease in the number of medications in all glaucoma index groups (GI), GI3 and GI4 showed the most significant changes (p<0.05) after 6 months postoperatively. †

GI = Glaucoma Index, ‡IOP: Intraocular pressure, §D: Day, ¶M: Month

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Figure 5. Intraocular pressure by visual field. Patients with advanced visual field damage had the lowest intraocular pressures starting at 1 month. †

GI = Glaucoma Index, ‡IOP: Intraocular pressure, §D: Day, ¶M: Month

Figure 6. Survival plot by glaucoma index group. Subjects had relatively similar survival rates. †

GI = Glaucoma Index

Page 20 of 29

Table 1. Demographics. Group 1: GI<3; group 2: 3≤GI<6; group 3: 6≤GI<12; group 4: GI≥12 _______________________________________________________________________ Group 1 n=103

Group 2 n=101

Group 3 n=168

Group 4 n=126

p-value 0.33

72±10 36 - 91

72±10 27 - 90

74±10 50 - 93 0.42

58 (57%) 43 (43%) 0 (0%)

85 (51%) 81 (48%) 2 (1%)

75 (60%) 49 (39%) 2 (2%) 0.08

er

Pe

5 (5%) 43 (43%) 49 (49%) 0 (0%) 4 (4%)

7 (4%) 61 (36%) 83 (49%) 2 (1%) 15 (9%)

4 (3%) 50 (40%) 63 (50%) 4 (3%) 5 (4%) 0.19

121 (72%) 24 (14%) 6 (4%) 9 (5%) 8 (5%)

vi

Re

75 (74%) 8 (8%) 5 (5%) 3 (3%) 10 (10%)

89 (71%) 25 (20%) 1 (1%) 6 (5%) 5 (4%) 0.01*

0.41±0.36 -0.19 - 2.00

0.35±0.35 0.54±0.62 -0.19 - 2.00 -0.19 - 3.00

0.70±0.19 0.2 - 1.0

0.75±0.15 0.4 - 1.0

ew

Age Mean±SD 73±10 Range 16 - 90 Gender Female 65 (63%) Male 37 (36%) Undocumented 1 (1%) Race 9 (9%) African American 29 (28%) Asian 61 (59%) Caucasian 1 (1%) Hispanic 3 (3%) Other Diagnosis POAG 77 (75%) Pseudoexfoliation Glaucoma 10 (10%) Pigment Dispersion 4 (4%) Steroid induced Glaucoma 4 (4%) Others 8 (8%) Visual Acuity (logMAR) Mean±SD 0.34±0.31 Range 0.00 - 2.00 Disc Cup/Disk Mean±SD 0.66±0.17 Range 0.1 - 0.99 Shaffer Grade I 2 (2%) II 9 (9%) III 32 (31%) IV 46 (45%) Undocumented 14 (14%)

r Fo

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

<0.01* 0.81±0.14 0.25 - 1.0 0.8

2 (2%) 5 (5%) 33 (33%) 47 (47%) 14 (14%)

0 (0%) 18 (11%) 60 (36%) 66 (39%) 24 (14%)

2 (2%) 14 (11%) 38 (30%) 55 (44%) 17 (13%)

________________________________________________________________________ †

GI = Glaucoma Index, ‡POAG = Primary Open-Angle Glaucoma

*p<0.05

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Table 2. Visual acuity (logMar) at baseline and after phaco-trabectome surgery. ________________________________________________________________________ GI1 Baseline 12 Month p-value

GI2

0.34±0.31 0.41±0.36 0.11±0.17 0.09±0.19 p<0.01* p<0.01*

GI3

GI4

0.35±0.35 0.16±0.26 p<0.01*

0.54±0.62 0.27±0.46 p<0.01*

________________________________________________________________________ †

GI = Glaucoma Index

*p<0.05

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Table 3. Univariate regression result. ________________________________________________________________________

Age Male Race Asian Caucasian Hispanic Other Diagnosis Others Pseudoexfoliation Glaucoma Pigmentary Dispersion Steroid Induced Glaucoma Cup/Disk Ratio Visual Acuity (logMAR) Shaffer Grade

Coefficient Standard Error p-value 0.06 0.03 0.03* -0.08 0.60 0.90 1.26 -0.21 3.88 0.50

1.33 1.31 2.65 1.73

0.34 0.87 0.14 0.77

0.00 -1.72 4.52 4.25 1.33 1.96 0.31

1.12 1.57 0.82 1.32 1.76 0.75 0.39

1.00 0.27 <0.01* <0.01* 0.43 0.01* 0.42

________________________________________________________________________ *p<0.05

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Table 4. Multivariate regression result. ________________________________________________________________________

GI Group Age Diagnosis Other Pigmentary Dispersion Pseudoexfoliation Glaucoma Steroid Induced Glaucoma Visual Acuity (logMAR)

Coefficient Standard Error p-value 1.69 0.24 <0.01* 0.05 0.03 0.08 0.47 -0.64 3.75 4.27 1.32

1.06 1.51 0.79 1.25 0.69

0.66 0.67 <0.01* <0.01* 0.06

________________________________________________________________________

†

GI = Glaucoma Index

*p<0.05

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Figure 1.

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Figure 2.

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Figure 3.

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Figure 4.

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Figure 5.

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Figure 6.