{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,6]],"date-time":"2026-05-06T11:12:30Z","timestamp":1778065950297,"version":"3.51.4"},"update-to":[{"DOI":"10.12688\/f1000research.8448.1","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2016,6,27]],"date-time":"2016-06-27T00:00:00Z","timestamp":1466985600000}}],"reference-count":23,"publisher":"F1000 Research Ltd","license":[{"start":{"date-parts":[[2016,6,27]],"date-time":"2016-06-27T00:00:00Z","timestamp":1466985600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["f1000research.com"],"crossmark-restriction":false},"short-container-title":["F1000Res"],"abstract":"<ns4:p>Prior glaucoma severity staging systems were mostly concerned with visual field function and retinal nerve fiber layer, but did not include intraocular pressure or medications to capture resistance to treatment. We recently introduced a simple index that combines pressure, medications, and visual field damage and applied it to stratify outcomes of trabectome surgery. In the analysis presented here, we combined data of trabectome alone and trabectome with same session cataract surgery to increase testing power and chances of effect discovery. This microincisional glaucoma surgery removes the primary resistance to outflow in glaucoma, the trabecular meshwork, and has been mostly used in mild glaucoma. Traditional glaucoma surgeries have a relatively high complication rate and have been reserved for more advanced disease stages. In the analysis presented here we include our data of trabectome combined with cataract surgery. This is a common practice pattern as both occur in the same age group with increasing frequency. For patients in higher glaucoma index (GI) groups, the intraocular pressure (IOP) reduction was 2.34+\/-0.19 mmHg more than those in a GI group one level lower while holding everything else constant. Those who had undergone trabectome combined with phacoemulsification had an IOP reduction that was 1.29+\/-0.39 mmHg less compared to those with trabectome alone. No statistically significant difference was found between genders and age groups while holding everything else constant. Hispanics had a 3.81+\/-1.08 mmHg greater IOP reduction. Pseudoexfoliation and steroid glaucoma patients had an IOP reduction that was greater by 2.91+\/-0.56 and 3.86+\/-0.81 mmHg, respectively, than those with primary open angle glaucoma. These results suggest a role for trabectome-mediated ab interno trabeculectomy beyond mild forms of glaucoma. Additionally, the multifactorial glaucoma index demonstrates a role in staging patients when comparing glaucoma surgical modalities.<\/ns4:p>","DOI":"10.12688\/f1000research.8448.2","type":"journal-article","created":{"date-parts":[[2016,6,27]],"date-time":"2016-06-27T06:05:29Z","timestamp":1467007529000},"page":"762","update-policy":"https:\/\/doi.org\/10.12688\/f1000research.crossmark-policy","source":"Crossref","is-referenced-by-count":15,"title":["Combined analysis of trabectome and phaco-trabectome outcomes by glaucoma severity"],"prefix":"10.12688","volume":"5","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2194-6375","authenticated-orcid":false,"given":"Yalong","family":"Dang","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pritha","family":"Roy","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0761-3320","authenticated-orcid":false,"given":"Igor I.","family":"Bussel","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ralitsa T.","family":"Loewen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hardik","family":"Parikh","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7167-1213","authenticated-orcid":false,"given":"Nils A.","family":"Loewen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"2560","published-online":{"date-parts":[[2016,6,27]]},"reference":[{"key":"ref-1","doi-asserted-by":"publisher","first-page":"110-7","DOI":"10.2174\/1874609811104020110","article-title":"Glaucoma and aging.","volume":"4","author":"G Guedes","year":"2011","journal-title":"Curr Aging Sci."},{"key":"ref-2","doi-asserted-by":"publisher","first-page":"417-24","DOI":"10.1016\/j.ophtha.2005.10.050","article-title":"Associations between elevated intraocular pressure and glaucoma, use of glaucoma medications, and 5-year incident cataract: the Blue Mountains Eye Study.","volume":"113","author":"S Chandrasekaran","year":"2006","journal-title":"Ophthalmology."},{"key":"ref-3","doi-asserted-by":"publisher","first-page":"15-20","DOI":"10.1097\/ICU.0b013e32835ab55f","article-title":"Incidence and management of cataract after glaucoma surgery.","volume":"24","author":"H 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Schuman","year":"1999","journal-title":"Invest Ophthalmol Vis Sci."},{"key":"ref-11","first-page":"41","article-title":"Intraocular pressure control through linked trabecular meshwork and collector channel motion","author":"M Johnstone","year":"2016"},{"key":"ref-12","doi-asserted-by":"publisher","first-page":"1233-40","DOI":"10.3109\/02713688909013902","article-title":"Outflow resistance of enucleated human eyes at two different perfusion pressures and different extents of trabeculotomy.","volume":"8","author":"R Rosenquist","year":"1989","journal-title":"Curr Eye Res."},{"key":"ref-13","doi-asserted-by":"publisher","first-page":"1-24","DOI":"10.1093\/pan\/mpr013","article-title":"Causal Inference without Balance Checking: Coarsened Exact Matching.","volume":"20","author":"S Iacus","year":"2012","journal-title":"Polit Anal."},{"key":"ref-14","doi-asserted-by":"publisher","first-page":"e0153585","DOI":"10.1371\/journal.pone.0153585","article-title":"Glaucoma Surgery Calculator: Limited 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Ophthalmol."}],"container-title":["F1000Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/f1000research.com\/articles\/5-762\/v2\/xml","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/f1000research.com\/articles\/5-762\/v2\/pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/f1000research.com\/articles\/5-762\/v2\/iparadigms","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,11,7]],"date-time":"2020-11-07T18:10:08Z","timestamp":1604772608000},"score":1,"resource":{"primary":{"URL":"https:\/\/f1000research.com\/articles\/5-762\/v2"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,6,27]]},"references-count":23,"URL":"https:\/\/doi.org\/10.12688\/f1000research.8448.2","relation":{"has-review":[{"id-type":"doi","id":"10.5256\/f1000research.9711.r14600","asserted-by":"subject"},{"id-type":"doi","id":"10.5256\/f1000research.9711.r14602","asserted-by":"subject"},{"id-type":"doi","id":"10.5256\/f1000research.9711.r14600","asserted-by":"object"},{"id-type":"doi","id":"10.5256\/f1000research.9711.r14602","asserted-by":"object"}]},"ISSN":["2046-1402"],"issn-type":[{"value":"2046-1402","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,6,27]]},"assertion":[{"value":"Indexed","URL":"https:\/\/f1000research.com\/articles\/5-762\/v2#article-reports","order":0,"name":"referee-status","label":"Referee status","group":{"name":"current-referee-status","label":"Current Referee Status"}},{"value":"10.5256\/f1000research.9096.r13590, Kristy G. Mascarenhas, Hartford Hospital\/Middlesex Hospital, Middletown, CT, USA, 10 May 2016, version 1, indexed","URL":"https:\/\/f1000research.com\/articles\/5-762\/v1#referee-response-13590","order":0,"name":"referee-response-13590","label":"Referee Report","group":{"name":"article-reports","label":"Article Reports"}},{"value":"<b>Nils Loewen<\/b>; \n<i>Posted: 09 Jun 2016<\/i>; \n<i>This was an interesting analysis of the use of Trabectome surgery in patients with more severe glaucomas. Comments and questions are as follows, most of which would clarify the methods and data analysis for the reader: The abstract and introduction could be clearer about the purpose of the study. &nbsp;You have to wait a long time to find out that this was a retrospective chart review of patients who had received Trabectome and phaco-Trabectome surgeries.<\/i>  \n<i>Were the authors looking for statistically significant differences in IOP reduction between the glaucoma severity groups, or equivalent effect in mild vs. severe glaucoma? &nbsp;<\/i> \n<i>If so, was a power calculation done?<\/i>  \n<b>Authors:<\/b> Thank you for the opportunity to revise our abstract and introduction. We have added to the abstract: \u201cIn the analysis presented here, we combined data of trabectome alone and trabectome with same session cataract surgery to increase testing power and chances of effect discovery.\u201d  We have also completely rewritten the introduction to explain &nbsp;the purpose of combining trabectome and phaco-trabectome data better and the idea behind the glaucoma index. Briefly, we recently created a simple glaucoma index that combines IOP, the number of medications and visual field status to gauge relative clinical glaucoma severity but also describes resistance to treatment. This may control for medication use when trying to gauge IOP results and allow to focus on glaucoma severity related outcomes. We combined trabectome and phaco-trabectome data sets because phacoemulsification is not a significant contributor to IOP reduction in studies with advanced matching strategies.  A power calculation was done and our regression analysis has a power of 0.95. &nbsp;We would require 82 patients to detect a GI IOP difference for a medium sized effect of 0.3 and a power of 80%. As our statistician advises, a power analysis is only needed when no statistical significance is found and that is why we had not reported it in our original submission. If a statistically significant difference is found as here, then that suggests that the statistical test is powerful enough.  \n<i>The abstract makes it sound as though only phaco-Trabectome cases were included, but the introduction states that both Trabectome and combined surgeries were included. Please clarify the abstract?<\/i>  \n<b>Authors:<\/b> Thank you for noticing this. Both were included and we have added the following to the abstract: \u201cIn the analysis presented here, we combined data of trabectome alone and trabectome with same session cataract surgery to increase testing power and chances of effect discovery.\u201d  \n<i>The methods section briefly introduces the glaucoma index system that was used, but especially for someone who has not read the previous article evaluating it, a bit more detail about the point system used would be helpful.<\/i>  \n<b>Authors:<\/b> We have updated our methods section to explain the individual factors in more detail: \u201cPatients were divided into four groups (from mild to severe) according to a glaucoma index (GI), an indicator of glaucoma severity based on visual field, the&nbsp;number of glaucoma medications, and preoperative IOP\n<sup>1<\/sup>. Baseline IOP was divided into 4 groups, &lt;20 mmHg, 20-29 mmHg, 30-39 mmHg, and above 40 and assigned with 1 to 4 points. Glaucoma medications (meds) were divided into 4 groups: \u22641, 2, 3, or \u22654, and assigned values of 1 to 4. Visual field (VF) was separated into 4 groups with points from 1 to 4: mild, moderate, advanced and end-stage. GI was then defined as VF*meds*IOP and separated into GI group 1 = mild, GI group 2 = moderate, GI group 3 = advanced, and GI4 = severe defined based on glaucoma index scores of \u201c\u22644\u201d, \u201c4&lt;GI\u22648\u201d, \u201c8&lt;GI\u226416\u201d, and \u201c&gt;16,\u201d respectively.\u201d  \n<i>One of the exclusion criteria was prior glaucoma surgery. Is data available about the number of patients who had previously had SLT\/ALT?<\/i>  Authors: Laser trabeculoplasty is the first line of treatment in our practice pattern, and this was not an exclusion criterion. Nearly all patients will have had this. Trabeculoplasty was not included as a factor in the analysis to reduce complexity. We have added to Methods: \u201cA history of laser trabeculoplasty did not lead to exclusion.\u201d  \n<i>Table 1 shows the number of Trabectomes vs. phaco\/Trabectomes. Did all phakic patients have cataract surgery, or did any receive Trabectome alone?<\/i>  \n<b>Authors: <\/b>We have analyzed the effect of trabectome in phakic patients before in two different studies\n<sup>2,3<\/sup> and found that even in narrow angles there does not seem to be a significant difference. Consequently, we included here all patients, including trabectome patients who remained phakic, to focus on the glaucoma index without further break down into subgroups.  It is important to recall that differences in phaco versus no phaco are merely based on averages. Because of a mixed indication for these patients (many cataract surgery patients do not need a pressure reduction and merely want to reduce medications) and because no formal matching was done, one cannot conclude from this study that cataract surgery is causatively linked to a diminished IOP reduction when compared to trabectome-only patients. On the contrary, an IOP reduction in many of our phaco-trabectome patients is simply not necessary to the same degree. \n<i>Over what time period did the reviewed patients receive Trabectome? Relatively recently, or closer to the beginning of Trabectome use? How many different surgeons' patients were reviewed? (Is it possible that surgical techniques evolved over time, or that different surgeons' techniques varied significantly?) &nbsp;A sentence like &quot;We reviewed the charts of XXX patients from XXX surgeons who underwent CE\/Trabectome or Trabectome alone between 2012-2016&quot; would be very helpful.<\/i>  \n<b>Authors: <\/b>The study period included data from 2011 up until the end of 2015. We did not analyze outcomes by individual surgeons. We concede that a majority of surgeries was performed by the senior author of this study and after 2012. Unfortunately, is not easily possible to provide the exact breakdown due to how data is extracted from the EMR data cloud. Manual curation of thousands of patient operative reports would be necessary.  \n<i>the authors state that patients in the severe GI group and patients with more severe glaucomas like pseudoexfoliation and steroid-response had a greater IOP reduction than other groups. Since IOP is one component of the glaucoma index and Trabectome does lower IOP more significantly with higher pre-op IOP, is it possible to say that Trabectome had a greater effect in these groups independently of pre-op IOP? (To confirm, was this analysis done?)<\/i>  \n<b>Authors:<\/b>\n<b> <\/b>Thank you very much for this inquiry. Without conducting a prospective, randomized controlled study or applying an advanced matching strategy, it is not possible to detect a strong, likely causative, correlation between glaucoma type and the&nbsp;amount of resulting IOP drop. The multivariate regression analysis we have done here does show that pseudoexfoliation and steroid glaucoma are significantly associated with a larger IOP reduction. This would be expected since both are obvious trabecular meshwork diseases. It is not clear what the substrate is that prevents IOP from &nbsp;reaching the theoretical limit of episcleral venous pressure after trabecular ablation or bypass.  The glaucoma index already captures resistance to medical treatment and these eyes require an IOP that is considerably lower than what can be achieved by trabecular ablation. This may reflect a tipping point.\n<sup>4<\/sup>  \n<i>Can the authors include a short discussion of limitations of the current study and possibly a bit of speculation on the smaller IOP reduction with phaco\/Trabectome than with Trabectome alone, as well as on why the more severe GI groups saw a shorter-lived IOP reduction?<\/i>  \n<b>Authors:<\/b>\n<b> <\/b>Thank you. We would like to add to the discussion the following: \u201cThis study has several limitations: to maximize patient number, we included all trabectome surgeries regardless of lens status or lens-cosurgery because our prior studies indicated that neither had a clinically relevant impact.\n<sup>2,3,5<\/sup> This study was limited to only one year when follow-up and data integrity was most amenable to automated retrieval and analysis. As a retrospective analysis, this study cannot discover causality and is only able to advise that patients with more severe glaucoma had a similar postoperative IOP and a comparable reduction in medications as those with mild glaucoma.\u201d  We have also added a better explanation why phaco-trabectome patients have a lesser IOP reduction: \u201cWe included here phaco-trabectome patients, who have a different, mixed indication that often includes a visually significant cataract as the primary motivator while presenting with a relatively stable glaucoma without the need for pressure reduction but a motivation to reduce medications. We did so after demonstrating by a rigorous statistical matching method, coarsened exact matching\n<sup>6<\/sup>, that phacoemulsification does not contribute significantly to IOP reduction when done at the same time \n<sup>7<\/sup> or in a surgery prior to trabectome surgery \n<sup>5<\/sup>. As in our prior studies \n<sup>5<\/sup>, phaco-trabectome patients had a lower preoperative IOP. This study focused on stratification of outcomes by glaucoma index and did not apply advanced matching strategies that we applied elsewhere \n<sup>5,7,8<\/sup> to compare two groups. Hence, one cannot conclude from this study that cataract surgery is causatively linked to a diminished IOP reduction when compared to trabectome-only patients. On the contrary, an IOP reduction in many of our phaco-trabectome patients is simply not necessary to the same degree.\u201d   \n<b>References used in this Reply to Reviewers<\/b>  Loewen, R. T. et al. Impact of a Glaucoma Severity Index on Results of Trabectome Surgery: Larger Pressure Reduction in More Severe Glaucoma. PLoS One 11, e0151926 (2016). &nbsp; Bussel, I. I., Kaplowitz, K., Schuman, J. S., Loewen, N. A. &amp; Trabectome Study Group. Outcomes of ab interno trabeculectomy with the trabectome by degree of angle opening. Br. J. Ophthalmol. 99, 914\u2013919 (2015). &nbsp; Parikh, H. A., Bussel, I. I., Schuman, J. S., Brown, E. N. &amp; Loewen, N. A. Coarsened Exact Matching of Phaco-Trabectome to Trabectome in Phakic Patients: Lack of Additional Pressure Reduction from Phacoemulsification. PLoS One 11, e0149384 (2016). &nbsp; Wollstein, G. et al. Retinal nerve fibre layer and visual function loss in glaucoma: the tipping point. Br. J. Ophthalmol. 96, 47\u201352 (2012). &nbsp; Neiweem, A. E., Bussel, I. I., Schuman, J. S., Brown, E. N. &amp; Loewen, N. A. Glaucoma Surgery Calculator: Limited Additive Effect of Phacoemulsification on Intraocular Pressure in Ab Interno Trabeculectomy. PLoS One 11, e0153585 (2016). &nbsp; Iacus, S. M., King, G. &amp; Porro, G. Causal Inference without Balance Checking: Coarsened Exact Matching. Polit. Anal. 20, 1\u201324 (2012). &nbsp; Parikh, H. A., Bussel, I. I., Schuman, J. S., Brown, E. N. &amp; Loewen, N. A. Coarsened Exact Matching of Phaco-Trabectome to Trabectome in Phakic Patients: Lack of Additional Pressure Reduction from Phacoemulsification. PLoS One 11, e0149384 (2016). &nbsp; Akil, H. et al. Clinical Results of Ab Interno Trabeculotomy Using the Trabectome in Patients with Pigmentary Glaucoma compared to Primary Open Angle Glaucoma. Clin. Experiment. Ophthalmol. (2016). doi:10.1111\/ceo.12737 &nbsp; Gedde, S. J. et al. in Am J Ophthalmol 153, 804\u2013814.e1 (2012 Elsevier Inc, 2012). &nbsp; Gedde, S. J. et al. Treatment Outcomes in the Tube Versus Trabeculectomy (TVT) Study After Five Years of Follow-up. Am. J. Ophthalmol. 153, 789\u2013803.e2 (2012). &nbsp; Taylor, H. R. Glaucoma: where to now? Ophthalmology 116, 821\u2013822 (2009). &nbsp; Rein, D. B. et al. The cost-effectiveness of routine office-based identification and subsequent medical treatment of primary open-angle glaucoma in the United States. Ophthalmology 116, 823\u2013832 (2009). &nbsp; Iordanous, Y., Kent, J. S., Hutnik, C. M. &amp; Malvankar-Mehta, M. S. Projected Cost Comparison of Trabectome, iStent, and Endoscopic Cyclophotocoagulation Versus Glaucoma Medication in the Ontario Health Insurance Plan. J. Glaucoma (2013). doi:10.1097\/IJG.0b013e31829d9bc7 &nbsp; Brusini, P. &amp; Filacorda, S. Enhanced Glaucoma Staging System (GSS 2) for classifying functional damage in glaucoma. J. Glaucoma 15, 40\u201346 (2006). &nbsp; Mills, R. P. et al. Categorizing the stage of glaucoma from pre-diagnosis to end-stage disease. Am. J. Ophthalmol. 141, 24\u201330 (2006). &nbsp; Advanced Glaucoma Intervention Study. 2. Visual field test scoring and reliability. Ophthalmology 101, 1445\u20131455 (1994). &nbsp; Zhang, X. et al. Predicting Development of Glaucomatous Visual Field Conversion Using Baseline Fourier-Domain Optical Coherence Tomography. Am. J. Ophthalmol. 163, 29\u201337 (2016).","URL":"https:\/\/f1000research.com\/articles\/5-762\/v2#referee-comment-2018","order":1,"name":"referee-comment-2018","label":"Referee Comment","group":{"name":"article-reports","label":"Article Reports"}},{"value":"10.5256\/f1000research.9711.r14602, William G. Myers, Department of Ophthalmology, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA, 27 Jun 2016, version 2, indexed","URL":"https:\/\/f1000research.com\/articles\/5-762\/v2#referee-response-14602","order":2,"name":"referee-response-14602","label":"Referee Report","group":{"name":"article-reports","label":"Article Reports"}},{"value":"10.5256\/f1000research.9711.r14600, Steven R. Sarkisian Jr., University of Oklahoma College of Medicine, Oklahoma City, OK, USA, 27 Jun 2016, version 2, indexed","URL":"https:\/\/f1000research.com\/articles\/5-762\/v2#referee-response-14600","order":3,"name":"referee-response-14600","label":"Referee Report","group":{"name":"article-reports","label":"Article Reports"}},{"value":"This study was funded by the Eye and Ear Foundation of Pittsburgh. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.","order":4,"name":"grant-information","label":"Grant Information"},{"value":"This is an open access article distributed under the terms of the Creative Commons Attribution Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.","order":0,"name":"copyright-info","label":"Copyright"}]}}