{"paper_id":"c348aeff-e78f-44cd-90af-52f989db3e79","body_text":"Comparison of corneal endothelial cell density reduction between primary open angle glaucoma and pseudo-exfoliation glaucoma patients at 3 years after Ex-Press® surgery | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Comparison of corneal endothelial cell density reduction between primary open angle glaucoma and pseudo-exfoliation glaucoma patients at 3 years after Ex-Press® surgery Hitoshi Yamazaki, Naoki Tojo, Mitsuya Otsuka, Tomoko Ueda-Consolvo, and 1 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4073890/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 23 Jul, 2024 Read the published version in International Ophthalmology → Version 1 posted 7 You are reading this latest preprint version Abstract Purpose We compared corneal endothelial cell (CED) loss between primary open angle glaucoma (POAG) and pseudo-exfoliation glaucoma (PEX) after Ex-Press (EXP) surgery. Patients and Methods: This was a single-facility retrospective study. We included patients who had undergone EXP surgery and were followed up > 3 years. We measured the CED before and after EXP surgery by noncontact specular microscopy. We measured the CED at baseline and 12, 24, and 36 months post-surgery and compared the means of the CED values and CED survival ratios after EXP surgery by paired t-test. Results We included 119 eyes that underwent EXP surgery: POAG group, n = 60 eyes; PEX group, n = 59 eyes. In the POAG group, the mean CED decreased from 2389 ± 321 at baseline to 2230 ± 424 cells/mm 2 after 3 years. In the PEX group, the mean CED decreased from 2111 ± 510 at baseline to 1845 ± 628 cells/mm 2 after 3 years. After the 3-year follow-up, the CED survival ratio was 93.3 ± 12.5% in the POAG group and significantly lower at 85.0 ± 19.5% in the PEX group (p = 0.0064). Two cases in the PEX group developed bullous keratopathy. Conclusions Compared to POAG, EXP surgery for PEX patients decreased their corneal endothelial cells faster. Ex-Press glaucoma corneal endothelial cell primary open angle glaucoma pseudo-exfoliation glaucoma INTRODUCTION An Ex-Press® shunt (Alcon Laboratories, Fort Worth, TX, USA) is filtration device for glaucoma surgery, and its use was approved in Japan in December 2011. EXP surgery entails a surgical method that is similar to a trabeculectomy (Trab) as filtration surgery, but EXP surgery has the advantages of not requiring trabecular meshwork removal or iris resection. There are many published comparisons of the surgical outcomes between Trab and EXP surgery, and most of these comparison indicated that the two methods' surgical outcomes were similar [ 1 – 4 ]. A single study reported that EXP surgery resulted in fewer postoperative complications [ 5 ]. Corneal endothelial cells maintain the transparency of the cornea. Persistent corneal edema (called 'bullous keratopathy') due to a reduction in the amount of corneal endothelial cells is one of the serious potential complications of filtration surgery such as Trab and Exp surgery. It has been suggested that EXP surgery could result in less corneal endothelial cell loss compared to trabeculectomies [ 6 , 7 ]. However, the findings regarding corneal endothelial cell reduction after EXP surgery are mixed for various glaucoma types [ 7 , 8 ]. We conducted the present study to evaluate the effects of EXP on corneal endothelial cell loss for each type of glaucoma. We compared the corneal endothelial cell density (CED) loss after EXP surgery between patients who had primary open angle glaucoma (POAG) and patients who had pseudo-exfoliation glaucoma (PEX). PATIENTS AND METHODS Patients This was a retrospective single-facility study. We included consecutive glaucoma patients who underwent EXP surgery for the first time at Toyama University Hospital and were followed for > 3 years. We excluded patients with glaucoma types other than POAG or PEX and excluded patients who had a history of conventional trabeculectomy, laser iridotomy, peripheral iridotomy, or keratoplasty. Since the focus of this study was the reduction of CED affected by filtration surgeries, we excluded patients who underwent additional glaucoma surgery. We included patients with a history of cataract surgery, trabeculotomy (TLO), selective laser trabeculoplasty (SLT), or vitrectomy before EXP surgery. We analyzed 119 eyes (101 patients) who underwent EXP surgery during the period from May 2013 to June 2018. We used binocular data for patients who underwent EXP surgery in both eyes. Since this study's design was retrospective, we did not define a distinct surgical indication for glaucoma or cataracts. The indication for surgery was determined based on the judgment of one glaucoma specialist (N.T.). The research protocol was approved by the Institutional Review Board of the University of Toyama (IRB No. R2023258), and the procedures used conformed to the tenets of the Declaration of Helsinki. After the nature and possible consequences of the study were explained to the patients, written informed consent was obtained from all individual participants included in the study. Surgical techniques All surgeries were performed by one surgeon (N.T.) who has abundant experience performing trabeculectomies and EXP surgeries. The EXP surgical method was as follows. All patients underwent the surgery under retrobulbar anesthesia. A fornix-based conjunctival incision was made, and a single 3.5-mm2 scleral flap was created. Mitomycin C (MMC) 0.04 mg/mL was applied below the conjunctiva and scleral flap for 4 min. and washed out with approx. 100 mL of balanced saline solution. In the cases of simultaneous cataract surgery, the cataract surgery was performed at this time. Phacoemulsification was performed with a WhiteStar Signature system (Johnson & Johnson, New Brunswick, NJ), and an intraocular lens (IOL) was implanted from the clear temporal cornea. Cataract surgery was performed based on the operator's judgment. A 25-ga. guide needle was inserted into the anterior chamber parallel to the iris at the trabecular meshwork, and an Ex-Press (model p50) shunt was then inserted into the anterior chamber. The scleral flap was sutured using 10 − 0 nylon with two stitches. The conjunctiva was sutured closed with 10 − 0 nylon to prevent leakage. Evaluation of the reduction rate of CED We examined the CED with an EM-4000 specular microscope (Tomey Corp., Nagoya, Japan). Each patient's CED was measured once preoperatively (baseline) and at 12, 24, and 36 months postsurgery. As for the measurement method, we measured CED at the center of cornea once and used the value automatically calculated by EM-400. We defined the survival ratio of CED as the ratio of post-operative CED to the pre-operative CED. Statistical analysis We used a paired t-test for comparisons between pairs of groups. JMP Pro 14 software (SAS, Cary, NC) was used for all of the statistical analyses. Significance was defined as a p-value < 0.05. RESULTS We analyzed a final total of 60 eyes (51 patients) in the POAG group and 59 eyes (50 patients) in the PEX group. The patients' ophthalmic data are summarized in Table 1 . The mean of the patients' age was significantly higher in the PEX group (74.2 ± 7.5 vs. 65.8 ± 10.4 in the POAG group, p < 0.0001). The percentage of patients who underwent simultaneous cataract surgery were significantly greater in the PEX group (48.3% vs. 18.6%, p = 0.0005). The patients' postoperative medications for glaucoma and the control of intraocular pressure (IOP) are listed in Tables 2 and 3 ; our analyses revealed that EXP surgery significantly decreased the IOP and the number of medications. There was no significant difference in the postoperative IOP values or the number of medications (p = 0.359) at 36 months between the POAG and PEX groups. Table 1 Patients' characteristics POAG (60 eyes) PEX (59 eyes) p-value Age, yrs 65.8 ± 10.4 74.2 ± 7.5 < 0.0001 Simultaneous cataract surgery, eyes 29/60 (48.3%) 11/59 (18.6%) 0.0005 CCT, µm 519 ± 32 530 ± 34 0.0594 Preoperative IOP, mmHg 21.2 ± 7.0 23.4 ± 8.0 0.143 Preoperative medications 4.0 ± 0.8 3.8 ± 1.0 0.151 Preoperative CED, cells/mm 2 2389 ± 321 2111 ± 510 0.0008 CCT: Central corneal thickness IOP: intraocular pressure. CED: corneal endothelial cells density Table 2 Comparison of postoperative IOP between Ex-press and trabeculectomy POAG PEX p-value preoperative 21.2 ± 7.0 23.4 ± 8.0 0.143 6 mos 9.7 ± 3.4 11.2 ± 3.6 0.0173 12 mos 10.2 ± 3.5 11.4 ± 3.2 0.0595 18 mos 10.7 ± 3.6 11.3 ± 2.7 0.325 24 mos 11.0 ± 3.6 11.4 ± 3.9 0.787 30 mos 10.9 ± 3.3 11.9 ± 3.3 0.133 36 mos 11.3 ± 3.9 11.6 ± 3.4 0.668 Data are mmHg. POAG: primary open angle glaucoma. PEX: pseudo-exfoliation glaucoma Table 3 The number of postoperative glaucoma medications POAG PEX p-value Preoperative 4.0 ± 0.8 3.8 ± 1.0 0.151 6 mos 0.7 ± 1.2 0.8 ± 1.5 0.664 12 mos 1.2 ± 1.6 1.3 ± 1.5 0.665 18 mos 1.4 ± 1.8 1.7 ± 1.6 0.373 24 mos 1.6 ± 1.8 1.9 ± 1.6 0.439 30 mos 2.3 ± 1.6 2.0 ± 1.6 0.392 36 mos 2.4 ± 1.5 2.1 ± 1.6 0.359 POAG: primary open angle glaucoma. PEX: pseudo-exfoliation glaucoma The results for the mean CED value and the CED survival ratio are presented in Table 4 . In the POAG group. the mean of the CED had decreased from 2389 ± 321 at baseline to 2230 ± 424 cells/mm 2 after 3 years whereas in the PEX group the mean of the CED had decreased from 2111 ± 510 at baseline to 1845 ± 628 cells/mm 2 after 3 years. The CED survival ratio at 36 months postsurgery was 93.3 ± 12.5% in the POAG group and significantly lower at 85.0 ± 19.5% in the PEX group (p = 0.0064). Two cases in the PEX group developed bullous keratopathy; their preoperative CED values were 645 and 1219 cells/mm2. Table 4 Corneal endothelial cell density and survival ratio Trab EXP p-value Preoperative CED, cells/mm 2 2389 ± 321 2111 ± 510 0.0008 12 mos CED, cells/mm 2 2333 ± 357 2048 ± 548 0.0011 24 mos CED, cells/mm 2 2284 ± 394 1953 ± 587 0.0005 36 mos CED, cells/mm 2 2230 ± 424 1845 ± 628 0.0002 12 mos Survival ratio, % 97.5 ± 7.4 95.3 ± 15.8 0.333 24 mos Survival ratio, % 95.5 ± 10.2 90.3 ± 17.2 0.0484 36 mos Survival ratio, % 93.3 ± 12.5 85.0 ± 19.5 0.0064 CED: endothelial corneal cells density Trab: trabeculectomy. EXP: Ex-Press surgery. Discussion The results of the is study demonstrated that Ex-Press surgery significantly decrease the IOP and the number of postoperative glaucoma medications in patients with glaucoma. After 3 years of follow-up, the mean postoperative IOP values were 11.3 mmHg in the POAG group and 11.6 mmHg in the PEX group. Regarding postoperative IOP, several studies of the results of EXP indicated that the patients' postoperative IOP was 13.2–14.7 mmHg after 3 years [ 1 , 2 , 4 ]. Our present patients' surgical outcomes included IOP values that are lower than those of the cited reports. One of the possible reasons for this discrepancy is that our patients' pre-operative IOP values were lower than those of the patients in the previous studies. Postoperative IOP values that are even lower than patient's low preoperative IOP values are needed. In the present study we excluded patients who underwent additional glaucoma surgery due to high postoperative IOP, and since we used data only from cases in which the surgery was successful, the postoperative IOP in our present patient series might be lower compared to those in earlier investigations. It is well known that glaucoma filtration surgery decreases the eye's CED. The mechanisms of CED reduction after EXP surgery might involve several factors, such as the effects of MMC, inflammation, and the abnormal aqueous humor flow [ 9 – 11 ]. The mean CED survival ratio in the present POAG group was 93.3%, and that in the PEX group was significantly lower at 85.0%. In other words, the reduction ratio was 6.7% in the POAG group and 15.0% in the PEX group. The CED outcomes after Ex-Press surgery have been described; for example, Arimura et al. reported that at 2 years after Ex-Press surgery, the CED was decreased by 18.0% [ 8 ], and Omatsu et al. observed that at 2 years after Ex-Press surgery, the patients' CED had decreased by 2.5% [ 7 ]. A meta-analysis revealed that Ex-Press surgery the CED had decreased by 8.11% after 2 years [ 5 ]. One of the reasons for such a wide range of CED loss values in these studies (i.e., 2.5%, 8.11%, and 18.0%) is that both POAG and PEX patients were included in their analyses. Aoyama et al. reported that at 3 years after patients with POAG underwent Ex-Press surgery, their mean CED had decreased by 5.4% [ 12 ]. Our present finding is comparable. An investigation by Lee et al. indicated that Ex-Press surgery decreased the CED of POAG patients by 10.0% over a 12-month period [ 6 ]. Although that investigation was limited to POAG patients, the results differ somewhat from ours. In an earlier study by our research group, we compared the CED loss between cornea insertion and trabecular meshwork insertion and observed that the mean CED-reduction ratio was 5.2% in trabecular meshwork insertion group and 15.1% in the corneal insertion group [ 13 ]. There is also a report indicating that peripheral anterior synechia (PAS) formation causes CED loss [ 14 ]. It is thus apparent that the causes of CED reduction are influenced by various factors. As previous reports, the mean CED value fell significantly faster in the PEX group [ 15 ]. It is important to know how much Ex-Press surgery will reduce the CED of patients with pseudo-exfoliation glaucoma (PEX), which tends to reduce the CED even without Ex-Press surgery. Higashide et al. reported that at 2 years postsurgery, trabeculectomy decreased the CED by 4.8% in their POAG group and by 18.2% in their PEX group [ 16 ]. Although it is well known that PEX is a factor that reduces CED, the underlying causes are unknown. There was a report that cytokines are involved [ 17 ]. Our study has some limitations. We included patients who had undergone cataract surgery, TLO, or SLT [ 18 – 20 ], and these surgeries affect the CED loss. Soro-Martínez et al. observed that trabeculectomy with simultaneous cataract surgery caused more endothelial cell damage than trabeculectomy alone [ 21 ]. We measured the present patients' CED only once at each timepoints. In addition, the measurement of the CED at the central cornea was not at exactly the same site in all cases, and measurement error is thus likely. It is desirable to measure the CED several times and use the average value. The number of patients in this study might also be too small to precisely evaluate the CED loss. In conclusion, Ex-Press surgery resulted in significantly lower IOP values and decreased the number of post-operative glaucoma medications for POAG and PEX patients similarly. The mean CED survival ratio was 93.3% in the patients with POAG and 85.0% in those with PEX. Ex-Press surgery decreased the CED significantly more quickly in the PEX patients compared to the POAG patients. Declarations Compliance with Ethical Standards Conflicts of interest: The authors declare that they have no conflicts of interest. Research involving human participants and/or animals: All procedures were performed in accord with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards, and ethical approval for this research was obtained from the Institutional Review Board of the University of Toyama. Informed consent: Informed consent was obtained from all individual participants included in the study. Funding: No funding was received. References Schultz SK, Iverson SM, Shi W, Greenfield DS. Safety and efficacy of achieving single-digit intraocular pressure targets with filtration surgery in eyes with progressive normal-tension glaucoma. J Glaucoma. 2016;25(2):217–22. Gonzalez-Rodriguez JM, Trope GE, Drori-Wagschal L, Jinapriya D, Buys YM. Comparison of trabeculectomy versus Ex-PRESS: 3-year follow-up. Br J Ophthalmol. 2016;100(9):1269–73. Arimura S, Takihara Y, Miyake S, Iwasaki K, Gozawa M, Matsumura T, et al. Randomized clinical trial for early postoperative complications of ex-press implantation versus trabeculectomy: Complications postoperatively of Ex-Press versus trabeculectomy Study (CPETS). Sci Rep. 2016;6:26080. Netland PA, Sarkisian SR, Jr., Moster MR, Ahmed, II, Condon G, Salim S, et al. Randomized, prospective, comparative trial of EX-Press glaucoma filtration device versus trabeculectomy (XVT study). Am J Ophthalmol. 2014;157(2):433–40 e3. Chen G, Li W, Jiang F, Mao S, Tong Y. Ex-PRESS implantation versus trabeculectomy in open-angle glaucoma: A meta-analysis of randomized controlled clinical trials. PLOS ONE. 2014;9(1):e86045. Lee GY, Lee CE, Lee KW, Seo S. Long-term efficacy and safety of ExPress implantation for treatment of open angle glaucoma. Int J Ophthalmol. 2017;10(9):1379–84. Omatsu S, Hirooka K, Nitta E, Ukegawa K. Changes in corneal endothelial cells after trabeculectomy and EX-PRESS shunt: 2-year follow-up. BMC Ophthalmol. 2018;18(1):243. Arimura S, Miyake S, Iwasaki K, Gozawa M, Matsumura T, Takamura Y, et al. Randomised clinical trial for postoperative complications after Ex-PRESS implantation versus trabeculectomy with 2-year follow-up. Sci Rep. 2018;8(1):16168. Storr-Paulsen T, Norregaard JC, Ahmed S, Storr-Paulsen A. Corneal endothelial cell loss after mitomycin C-augmented trabeculectomy. J Glaucoma. 2008;17(8):654–7. Macdonald JM, Geroski DH, Edelhauser HF. Effect of inflammation on the corneal endothelial pump and barrier. Curr Eye Res. 1987;6(9):1125–32. McDermott ML, Swendris RP, Shin DH, Juzych MS, Cowden JW. Corneal endothelial cell counts after Molteno implantation. Am J Ophthalmol. 1993;115(1):93–6. Aoyama Y, Sakata R, Fujishiro T, Honjo M, Shirato S, Aihara M. Changes in corneal endothelial cell density after initial Ex-Press drainage device implantation and its relating factors over 3 years. Eye. 2023;37(1):69–74. Otsuka M, Tojo N, Hayashi A. Corneal endothelial cell loss after Ex-Press surgery depends on site of insertion, cornea or trabecular meshwork. Int Ophthalmol. 2023;43(10):3471–7. Rowsey JJ, Gaylor JR. Intraocular lens disasters: Peripheral anterior synechia. Ophthalmology. 1980;87(7):646–64. Hasegawa Y, Nejima R, Mori Y, Sakisaka T, Minami K, Miyata K, et al. Risk factors for corneal endothelial cell loss by cataract surgery in eyes with pseudoexfoliation syndrome. Clin Ophthalmol. 2016;10:1685–9. Higashide T, Nishino T, Sakaguchi K, Yamada Y, Sugiyama K. Determinants of corneal endothelial cell loss after trabeculectomy with mitomycin C. J Glaucoma. 2019;28(1):61–7. Djordjević-Jocić J, Zlatanovic G, Veselinovic D, Jovanovic P, Djordjevic V, Zvezdanovic L, et al. Transforming growth factor beta1, matrix-metalloproteinase-2 and its tissue inhibitor in patients with pseudoexfoliation glaucoma/syndrome. Vojnosanit Pregl. 2012;69(3):231–6. Bourne RR, Minassian DC, Dart JK, Rosen P, Kaushal S, Wingate N. Effect of cataract surgery on the corneal endothelium: Modern phacoemulsification compared with extracapsular cataract surgery. Ophthalmology. 2004;111(4):679–85. Kasahara M, Shoji N, Matsumura K. The influence of trabectome surgery on corneal endothelial cells. J Glaucoma. 2019;28(2):150–3. Leahy KE, Madigan MC, Sarris M, Watson SL, McCluskey P, White AJ. Investigation of corneal endothelial changes post selective laser trabeculoplasty. Clin Exp Ophthalmol. 2018;46(7):730–7. Soro-Martinez MI, Villegas-Perez MP, Sobrado-Calvo P, Ruiz-Gomez JM, Miralles de Imperial Mora-Figueroa J. Corneal endothelial cell loss after trabeculectomy or after phacoemulsification, IOL implantation and trabeculectomy in 1 or 2 steps. Graefes Arch Clin Exp Ophthalmol. 2010;248(2):249–56. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Published Journal Publication published 23 Jul, 2024 Read the published version in International Ophthalmology → Version 1 posted Editorial decision: Revision requested 01 May, 2024 Reviews received at journal 28 Apr, 2024 Reviewers agreed at journal 25 Apr, 2024 Reviewers invited by journal 24 Apr, 2024 Editor assigned by journal 12 Mar, 2024 Submission checks completed at journal 11 Mar, 2024 First submitted to journal 11 Mar, 2024 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {\"props\":{\"pageProps\":{\"initialData\":{\"identity\":\"rs-4073890\",\"acceptedTermsAndConditions\":true,\"allowDirectSubmit\":false,\"archivedVersions\":[],\"articleType\":\"Research Article\",\"associatedPublications\":[],\"authors\":[{\"id\":278702278,\"identity\":\"188f635e-15b2-4956-bf77-a074e3ca6fc7\",\"order_by\":0,\"name\":\"Hitoshi Yamazaki\",\"email\":\"\",\"orcid\":\"\",\"institution\":\"University of Toyama\",\"correspondingAuthor\":false,\"prefix\":\"\",\"firstName\":\"Hitoshi\",\"middleName\":\"\",\"lastName\":\"Yamazaki\",\"suffix\":\"\"},{\"id\":278702279,\"identity\":\"7a357ec8-a5a4-4637-a91a-42eadf2daa6e\",\"order_by\":1,\"name\":\"Naoki Tojo\",\"email\":\"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA+klEQVRIiWNgGAWjYHCCBIYPBhL1DAzMBxgYG6BiEnjU8wC1MM6osElgYGBLIFoLAzPPmTSgFh4DhBZ8wJ694eED3rbDeeZiZ75J/NxhI8fAfvgAg+UOPLbwHEg2kGw7XGw5O3ebZO+ZNGMGHqCVkmfwaJFISJMwbDvMuOF27jYJoHWJDRJAF0q2EdCSCNaS80zyL9FaDpxJSwRqYZMmzpYzB5INGypsjA1upxlby7alGbMB/XIAn1/Y23sSH/8xkJAzuJ388ObbNhs5fvbDBx9L4gkxoD0JMBYLOALZgPiwZAM+LewHYCzmDzAW40e8WkbBKBgFo2CEAQBjh1HsYPrNkgAAAABJRU5ErkJggg==\",\"orcid\":\"\",\"institution\":\"University of Toyama\",\"correspondingAuthor\":true,\"prefix\":\"\",\"firstName\":\"Naoki\",\"middleName\":\"\",\"lastName\":\"Tojo\",\"suffix\":\"\"},{\"id\":278702280,\"identity\":\"f3d9c0c4-055c-438d-ab23-ae47bcae9d8f\",\"order_by\":2,\"name\":\"Mitsuya Otsuka\",\"email\":\"\",\"orcid\":\"\",\"institution\":\"University of Toyama\",\"correspondingAuthor\":false,\"prefix\":\"\",\"firstName\":\"Mitsuya\",\"middleName\":\"\",\"lastName\":\"Otsuka\",\"suffix\":\"\"},{\"id\":278702281,\"identity\":\"d9297af4-eba2-4833-b9be-437de83eee92\",\"order_by\":3,\"name\":\"Tomoko Ueda-Consolvo\",\"email\":\"\",\"orcid\":\"\",\"institution\":\"University of Toyama\",\"correspondingAuthor\":false,\"prefix\":\"\",\"firstName\":\"Tomoko\",\"middleName\":\"\",\"lastName\":\"Ueda-Consolvo\",\"suffix\":\"\"},{\"id\":278702282,\"identity\":\"1c3b2e43-fdcb-4c60-9e57-54ce7922ac99\",\"order_by\":4,\"name\":\"Atsushi Hayashi\",\"email\":\"\",\"orcid\":\"\",\"institution\":\"University of Toyama\",\"correspondingAuthor\":false,\"prefix\":\"\",\"firstName\":\"Atsushi\",\"middleName\":\"\",\"lastName\":\"Hayashi\",\"suffix\":\"\"}],\"badges\":[],\"createdAt\":\"2024-03-11 12:48:53\",\"currentVersionCode\":1,\"declarations\":\"\",\"doi\":\"10.21203/rs.3.rs-4073890/v1\",\"doiUrl\":\"https://doi.org/10.21203/rs.3.rs-4073890/v1\",\"draftVersion\":[],\"editorialEvents\":[{\"content\":\"https://doi.org/10.1007/s10792-024-03248-w\",\"type\":\"published\",\"date\":\"2024-07-23T16:16:13+00:00\"}],\"editorialNote\":\"\",\"failedWorkflow\":false,\"files\":[{\"id\":61596180,\"identity\":\"196bb276-73df-42ba-98f0-929b676d0228\",\"added_by\":\"auto\",\"created_at\":\"2024-08-01 17:25:27\",\"extension\":\"pdf\",\"order_by\":0,\"title\":\"\",\"display\":\"\",\"copyAsset\":false,\"role\":\"manuscript-pdf\",\"size\":407325,\"visible\":true,\"origin\":\"\",\"legend\":\"\",\"description\":\"\",\"filename\":\"manuscript.pdf\",\"url\":\"https://assets-eu.researchsquare.com/files/rs-4073890/v1/a8844157-cdf6-46ef-8d20-8c4371952746.pdf\"}],\"financialInterests\":\"No competing interests reported.\",\"formattedTitle\":\"Comparison of corneal endothelial cell density reduction between primary open angle glaucoma and pseudo-exfoliation glaucoma patients at 3 years after Ex-Press® surgery\",\"fulltext\":[{\"header\":\"INTRODUCTION\",\"content\":\"\\u003cp\\u003eAn Ex-Press\\u0026reg; shunt (Alcon Laboratories, Fort Worth, TX, USA) is filtration device for glaucoma surgery, and its use was approved in Japan in December 2011. EXP surgery entails a surgical method that is similar to a trabeculectomy (Trab) as filtration surgery, but EXP surgery has the advantages of not requiring trabecular meshwork removal or iris resection. There are many published comparisons of the surgical outcomes between Trab and EXP surgery, and most of these comparison indicated that the two methods' surgical outcomes were similar [\\u003cspan additionalcitationids=\\\"CR2 CR3\\\" citationid=\\\"CR1\\\" class=\\\"CitationRef\\\"\\u003e1\\u003c/span\\u003e\\u0026ndash;\\u003cspan citationid=\\\"CR4\\\" class=\\\"CitationRef\\\"\\u003e4\\u003c/span\\u003e]. A single study reported that EXP surgery resulted in fewer postoperative complications [\\u003cspan citationid=\\\"CR5\\\" class=\\\"CitationRef\\\"\\u003e5\\u003c/span\\u003e].\\u003c/p\\u003e \\u003cp\\u003eCorneal endothelial cells maintain the transparency of the cornea. Persistent corneal edema (called 'bullous keratopathy') due to a reduction in the amount of corneal endothelial cells is one of the serious potential complications of filtration surgery such as Trab and Exp surgery. It has been suggested that EXP surgery could result in less corneal endothelial cell loss compared to trabeculectomies [\\u003cspan citationid=\\\"CR6\\\" class=\\\"CitationRef\\\"\\u003e6\\u003c/span\\u003e, \\u003cspan citationid=\\\"CR7\\\" class=\\\"CitationRef\\\"\\u003e7\\u003c/span\\u003e]. However, the findings regarding corneal endothelial cell reduction after EXP surgery are mixed for various glaucoma types [\\u003cspan citationid=\\\"CR7\\\" class=\\\"CitationRef\\\"\\u003e7\\u003c/span\\u003e, \\u003cspan citationid=\\\"CR8\\\" class=\\\"CitationRef\\\"\\u003e8\\u003c/span\\u003e]. We conducted the present study to evaluate the effects of EXP on corneal endothelial cell loss for each type of glaucoma. We compared the corneal endothelial cell density (CED) loss after EXP surgery between patients who had primary open angle glaucoma (POAG) and patients who had pseudo-exfoliation glaucoma (PEX).\\u003c/p\\u003e\"},{\"header\":\"PATIENTS AND METHODS\",\"content\":\"\\u003cdiv id=\\\"Sec3\\\" class=\\\"Section2\\\"\\u003e \\u003ch2\\u003ePatients\\u003c/h2\\u003e \\u003cp\\u003eThis was a retrospective single-facility study. We included consecutive glaucoma patients who underwent EXP surgery for the first time at Toyama University Hospital and were followed for \\u0026gt;\\u0026thinsp;3 years. We excluded patients with glaucoma types other than POAG or PEX and excluded patients who had a history of conventional trabeculectomy, laser iridotomy, peripheral iridotomy, or keratoplasty. Since the focus of this study was the reduction of CED affected by filtration surgeries, we excluded patients who underwent additional glaucoma surgery. We included patients with a history of cataract surgery, trabeculotomy (TLO), selective laser trabeculoplasty (SLT), or vitrectomy before EXP surgery.\\u003c/p\\u003e \\u003cp\\u003eWe analyzed 119 eyes (101 patients) who underwent EXP surgery during the period from May 2013 to June 2018. We used binocular data for patients who underwent EXP surgery in both eyes. Since this study's design was retrospective, we did not define a distinct surgical indication for glaucoma or cataracts. The indication for surgery was determined based on the judgment of one glaucoma specialist (N.T.). The research protocol was approved by the Institutional Review Board of the University of Toyama (IRB No. R2023258), and the procedures used conformed to the tenets of the Declaration of Helsinki. After the nature and possible consequences of the study were explained to the patients, written informed consent was obtained from all individual participants included in the study.\\u003c/p\\u003e \\u003cdiv id=\\\"Sec4\\\" class=\\\"Section3\\\"\\u003e \\u003ch2\\u003eSurgical techniques\\u003c/h2\\u003e \\u003cp\\u003eAll surgeries were performed by one surgeon (N.T.) who has abundant experience performing trabeculectomies and EXP surgeries. The EXP surgical method was as follows. All patients underwent the surgery under retrobulbar anesthesia. A fornix-based conjunctival incision was made, and a single 3.5-mm2 scleral flap was created. Mitomycin C (MMC) 0.04 mg/mL was applied below the conjunctiva and scleral flap for 4 min. and washed out with approx. 100 mL of balanced saline solution. In the cases of simultaneous cataract surgery, the cataract surgery was performed at this time. Phacoemulsification was performed with a WhiteStar Signature system (Johnson \\u0026amp; Johnson, New Brunswick, NJ), and an intraocular lens (IOL) was implanted from the clear temporal cornea. Cataract surgery was performed based on the operator's judgment. A 25-ga. guide needle was inserted into the anterior chamber parallel to the iris at the trabecular meshwork, and an Ex-Press (model p50) shunt was then inserted into the anterior chamber. The scleral flap was sutured using 10\\u0026thinsp;\\u0026minus;\\u0026thinsp;0 nylon with two stitches. The conjunctiva was sutured closed with 10\\u0026thinsp;\\u0026minus;\\u0026thinsp;0 nylon to prevent leakage.\\u003c/p\\u003e \\u003c/div\\u003e \\u003c/div\\u003e \\u003cdiv id=\\\"Sec5\\\" class=\\\"Section2\\\"\\u003e \\u003ch2\\u003eEvaluation of the reduction rate of CED\\u003c/h2\\u003e \\u003cp\\u003eWe examined the CED with an EM-4000 specular microscope (Tomey Corp., Nagoya, Japan). Each patient's CED was measured once preoperatively (baseline) and at 12, 24, and 36 months postsurgery. As for the measurement method, we measured CED at the center of cornea once and used the value automatically calculated by EM-400. We defined the survival ratio of CED as the ratio of post-operative CED to the pre-operative CED.\\u003c/p\\u003e \\u003c/div\\u003e \\u003cdiv id=\\\"Sec6\\\" class=\\\"Section2\\\"\\u003e \\u003ch2\\u003eStatistical analysis\\u003c/h2\\u003e \\u003cp\\u003eWe used a paired t-test for comparisons between pairs of groups. JMP Pro 14 software (SAS, Cary, NC) was used for all of the statistical analyses. Significance was defined as a p-value\\u0026thinsp;\\u0026lt;\\u0026thinsp;0.05.\\u003c/p\\u003e \\u003c/div\\u003e\"},{\"header\":\"RESULTS\",\"content\":\"\\u003cp\\u003eWe analyzed a final total of 60 eyes (51 patients) in the POAG group and 59 eyes (50 patients) in the PEX group. The patients' ophthalmic data are summarized in Table\\u0026nbsp;\\u003cspan refid=\\\"Tab1\\\" class=\\\"InternalRef\\\"\\u003e1\\u003c/span\\u003e. The mean of the patients' age was significantly higher in the PEX group (74.2\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;7.5 vs. 65.8\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;10.4 in the POAG group, p\\u0026thinsp;\\u0026lt;\\u0026thinsp;0.0001). The percentage of patients who underwent simultaneous cataract surgery were significantly greater in the PEX group (48.3% vs. 18.6%, p\\u0026thinsp;=\\u0026thinsp;0.0005). The patients' postoperative medications for glaucoma and the control of intraocular pressure (IOP) are listed in Tables\\u0026nbsp;\\u003cspan refid=\\\"Tab2\\\" class=\\\"InternalRef\\\"\\u003e2\\u003c/span\\u003e and \\u003cspan refid=\\\"Tab3\\\" class=\\\"InternalRef\\\"\\u003e3\\u003c/span\\u003e; our analyses revealed that EXP surgery significantly decreased the IOP and the number of medications. There was no significant difference in the postoperative IOP values or the number of medications (p\\u0026thinsp;=\\u0026thinsp;0.359) at 36 months between the POAG and PEX groups.\\u003c/p\\u003e \\u003cp\\u003e \\u003cdiv class=\\\"gridtable\\\"\\u003e\\u003ctable float=\\\"Yes\\\" id=\\\"Tab1\\\" border=\\\"1\\\"\\u003e \\u003ccaption language=\\\"En\\\"\\u003e \\u003cdiv class=\\\"CaptionNumber\\\"\\u003eTable 1\\u003c/div\\u003e \\u003cdiv class=\\\"CaptionContent\\\"\\u003e \\u003cp\\u003ePatients' characteristics\\u003c/p\\u003e \\u003c/div\\u003e \\u003c/caption\\u003e \\u003ccolgroup cols=\\\"4\\\"\\u003e \\u003cdiv align=\\\"left\\\" class=\\\"colspec\\\" colname=\\\"c1\\\" colnum=\\\"1\\\"\\u003e\\u003c/div\\u003e \\u003cdiv align=\\\"left\\\" class=\\\"colspec\\\" colname=\\\"c2\\\" colnum=\\\"2\\\"\\u003e\\u003c/div\\u003e \\u003cdiv align=\\\"left\\\" class=\\\"colspec\\\" colname=\\\"c3\\\" colnum=\\\"3\\\"\\u003e\\u003c/div\\u003e \\u003cdiv align=\\\"char\\\" char=\\\".\\\" class=\\\"colspec\\\" colname=\\\"c4\\\" colnum=\\\"4\\\"\\u003e\\u003c/div\\u003e \\u003cthead\\u003e \\u003ctr\\u003e \\u003cth align=\\\"left\\\" colname=\\\"c1\\\"\\u003e\\u0026nbsp;\\u003c/th\\u003e \\u003cth align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003ePOAG\\u003c/p\\u003e \\u003cp\\u003e(60 eyes)\\u003c/p\\u003e \\u003c/th\\u003e \\u003cth align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003ePEX\\u003c/p\\u003e \\u003cp\\u003e(59 eyes)\\u003c/p\\u003e \\u003c/th\\u003e \\u003cth align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003ep-value\\u003c/p\\u003e \\u003c/th\\u003e \\u003c/tr\\u003e \\u003c/thead\\u003e \\u003ctbody\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eAge, yrs\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e65.8\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;10.4\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e74.2\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;7.5\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e\\u0026lt;\\u0026thinsp;0.0001\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eSimultaneous cataract surgery, eyes\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e29/60 (48.3%)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e11/59 (18.6%)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e0.0005\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eCCT, \\u0026micro;m\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e519\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;32\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e530\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;34\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e0.0594\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003ePreoperative IOP, mmHg\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e21.2\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;7.0\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e23.4\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;8.0\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e0.143\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003ePreoperative medications\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e4.0\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;0.8\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e3.8\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;1.0\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e0.151\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003ePreoperative CED, cells/mm\\u003csup\\u003e2\\u003c/sup\\u003e\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e2389\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;321\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e2111\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;510\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e0.0008\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003c/tbody\\u003e \\u003c/colgroup\\u003e \\u003ctfoot\\u003e \\u003ctr\\u003e\\u003ctd colspan=\\\"4\\\"\\u003eCCT: Central corneal thickness\\u003c/td\\u003e\\u003c/tr\\u003e \\u003ctr\\u003e\\u003ctd colspan=\\\"4\\\"\\u003eIOP: intraocular pressure.\\u003c/td\\u003e\\u003c/tr\\u003e \\u003ctr\\u003e\\u003ctd colspan=\\\"4\\\"\\u003eCED: corneal endothelial cells density\\u003c/td\\u003e\\u003c/tr\\u003e \\u003c/tfoot\\u003e \\u003c/table\\u003e\\u003c/div\\u003e \\u003c/p\\u003e \\u003cp\\u003e \\u003cdiv class=\\\"gridtable\\\"\\u003e\\u003ctable float=\\\"Yes\\\" id=\\\"Tab2\\\" border=\\\"1\\\"\\u003e \\u003ccaption language=\\\"En\\\"\\u003e \\u003cdiv class=\\\"CaptionNumber\\\"\\u003eTable 2\\u003c/div\\u003e \\u003cdiv class=\\\"CaptionContent\\\"\\u003e \\u003cp\\u003eComparison of postoperative IOP between Ex-press and trabeculectomy\\u003c/p\\u003e \\u003c/div\\u003e \\u003c/caption\\u003e \\u003ccolgroup cols=\\\"4\\\"\\u003e \\u003cdiv align=\\\"left\\\" class=\\\"colspec\\\" colname=\\\"c1\\\" colnum=\\\"1\\\"\\u003e\\u003c/div\\u003e \\u003cdiv align=\\\"char\\\" char=\\\"\\u0026plusmn;\\\" class=\\\"colspec\\\" colname=\\\"c2\\\" colnum=\\\"2\\\"\\u003e\\u003c/div\\u003e \\u003cdiv align=\\\"char\\\" char=\\\"\\u0026plusmn;\\\" class=\\\"colspec\\\" colname=\\\"c3\\\" colnum=\\\"3\\\"\\u003e\\u003c/div\\u003e \\u003cdiv align=\\\"char\\\" char=\\\".\\\" class=\\\"colspec\\\" colname=\\\"c4\\\" colnum=\\\"4\\\"\\u003e\\u003c/div\\u003e \\u003cthead\\u003e \\u003ctr\\u003e \\u003cth align=\\\"left\\\" colname=\\\"c1\\\"\\u003e\\u0026nbsp;\\u003c/th\\u003e \\u003cth align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003ePOAG\\u003c/p\\u003e \\u003c/th\\u003e \\u003cth align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003ePEX\\u003c/p\\u003e \\u003c/th\\u003e \\u003cth align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003ep-value\\u003c/p\\u003e \\u003c/th\\u003e \\u003c/tr\\u003e \\u003c/thead\\u003e \\u003ctbody\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003epreoperative\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\"\\u0026plusmn;\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e21.2\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;7.0\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\"\\u0026plusmn;\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e23.4\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;8.0\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e0.143\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003e6 mos\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\"\\u0026plusmn;\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e9.7\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;3.4\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\"\\u0026plusmn;\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e11.2\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;3.6\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e0.0173\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003e12 mos\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\"\\u0026plusmn;\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e10.2\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;3.5\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\"\\u0026plusmn;\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e11.4\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;3.2\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e0.0595\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003e18 mos\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\"\\u0026plusmn;\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e10.7\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;3.6\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\"\\u0026plusmn;\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e11.3\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;2.7\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e0.325\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003e24 mos\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\"\\u0026plusmn;\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e11.0\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;3.6\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\"\\u0026plusmn;\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e11.4\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;3.9\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e0.787\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003e30 mos\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\"\\u0026plusmn;\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e10.9\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;3.3\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\"\\u0026plusmn;\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e11.9\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;3.3\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e0.133\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003e36 mos\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\"\\u0026plusmn;\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e11.3\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;3.9\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\"\\u0026plusmn;\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e11.6\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;3.4\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e0.668\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003c/tbody\\u003e \\u003c/colgroup\\u003e \\u003ctfoot\\u003e \\u003ctr\\u003e\\u003ctd colspan=\\\"4\\\"\\u003eData are mmHg.\\u003c/td\\u003e\\u003c/tr\\u003e \\u003ctr\\u003e\\u003ctd colspan=\\\"4\\\"\\u003ePOAG: primary open angle glaucoma.\\u003c/td\\u003e\\u003c/tr\\u003e \\u003ctr\\u003e\\u003ctd colspan=\\\"4\\\"\\u003ePEX: pseudo-exfoliation glaucoma\\u003c/td\\u003e\\u003c/tr\\u003e \\u003c/tfoot\\u003e \\u003c/table\\u003e\\u003c/div\\u003e \\u003c/p\\u003e \\u003cp\\u003e \\u003cdiv class=\\\"gridtable\\\"\\u003e\\u003ctable float=\\\"Yes\\\" id=\\\"Tab3\\\" border=\\\"1\\\"\\u003e \\u003ccaption language=\\\"En\\\"\\u003e \\u003cdiv class=\\\"CaptionNumber\\\"\\u003eTable 3\\u003c/div\\u003e \\u003cdiv class=\\\"CaptionContent\\\"\\u003e \\u003cp\\u003eThe number of postoperative glaucoma medications\\u003c/p\\u003e \\u003c/div\\u003e \\u003c/caption\\u003e \\u003ccolgroup cols=\\\"4\\\"\\u003e \\u003cdiv align=\\\"left\\\" class=\\\"colspec\\\" colname=\\\"c1\\\" colnum=\\\"1\\\"\\u003e\\u003c/div\\u003e \\u003cdiv align=\\\"char\\\" char=\\\"\\u0026plusmn;\\\" class=\\\"colspec\\\" colname=\\\"c2\\\" colnum=\\\"2\\\"\\u003e\\u003c/div\\u003e \\u003cdiv align=\\\"char\\\" char=\\\"\\u0026plusmn;\\\" class=\\\"colspec\\\" colname=\\\"c3\\\" colnum=\\\"3\\\"\\u003e\\u003c/div\\u003e \\u003cdiv align=\\\"char\\\" char=\\\".\\\" class=\\\"colspec\\\" colname=\\\"c4\\\" colnum=\\\"4\\\"\\u003e\\u003c/div\\u003e \\u003cthead\\u003e \\u003ctr\\u003e \\u003cth align=\\\"left\\\" colname=\\\"c1\\\"\\u003e\\u0026nbsp;\\u003c/th\\u003e \\u003cth align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003ePOAG\\u003c/p\\u003e \\u003c/th\\u003e \\u003cth align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003ePEX\\u003c/p\\u003e \\u003c/th\\u003e \\u003cth align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003ep-value\\u003c/p\\u003e \\u003c/th\\u003e \\u003c/tr\\u003e \\u003c/thead\\u003e \\u003ctbody\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003ePreoperative\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\"\\u0026plusmn;\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e4.0\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;0.8\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\"\\u0026plusmn;\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e3.8\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;1.0\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e0.151\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003e6 mos\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\"\\u0026plusmn;\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e0.7\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;1.2\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\"\\u0026plusmn;\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e0.8\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;1.5\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e0.664\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003e12 mos\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\"\\u0026plusmn;\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e1.2\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;1.6\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\"\\u0026plusmn;\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e1.3\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;1.5\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e0.665\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003e18 mos\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\"\\u0026plusmn;\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e1.4\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;1.8\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\"\\u0026plusmn;\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e1.7\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;1.6\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e0.373\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003e24 mos\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\"\\u0026plusmn;\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e1.6\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;1.8\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\"\\u0026plusmn;\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e1.9\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;1.6\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e0.439\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003e30 mos\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\"\\u0026plusmn;\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e2.3\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;1.6\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\"\\u0026plusmn;\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e2.0\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;1.6\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e0.392\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003e36 mos\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\"\\u0026plusmn;\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e2.4\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;1.5\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\"\\u0026plusmn;\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e2.1\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;1.6\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e0.359\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003c/tbody\\u003e \\u003c/colgroup\\u003e \\u003ctfoot\\u003e \\u003ctr\\u003e\\u003ctd colspan=\\\"4\\\"\\u003ePOAG: primary open angle glaucoma.\\u003c/td\\u003e\\u003c/tr\\u003e \\u003ctr\\u003e\\u003ctd colspan=\\\"4\\\"\\u003ePEX: pseudo-exfoliation glaucoma\\u003c/td\\u003e\\u003c/tr\\u003e \\u003c/tfoot\\u003e \\u003c/table\\u003e\\u003c/div\\u003e \\u003c/p\\u003e \\u003cp\\u003eThe results for the mean CED value and the CED survival ratio are presented in Table\\u0026nbsp;\\u003cspan refid=\\\"Tab4\\\" class=\\\"InternalRef\\\"\\u003e4\\u003c/span\\u003e. In the POAG group. the mean of the CED had decreased from 2389\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;321 at baseline to 2230\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;424 cells/mm\\u003csup\\u003e2\\u003c/sup\\u003e after 3 years whereas in the PEX group the mean of the CED had decreased from 2111\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;510 at baseline to 1845\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;628 cells/mm\\u003csup\\u003e2\\u003c/sup\\u003e after 3 years. The CED survival ratio at 36 months postsurgery was 93.3\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;12.5% in the POAG group and significantly lower at 85.0\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;19.5% in the PEX group (p\\u0026thinsp;=\\u0026thinsp;0.0064). Two cases in the PEX group developed bullous keratopathy; their preoperative CED values were 645 and 1219 cells/mm2.\\u003c/p\\u003e \\u003cp\\u003e \\u003cdiv class=\\\"gridtable\\\"\\u003e\\u003ctable float=\\\"Yes\\\" id=\\\"Tab4\\\" border=\\\"1\\\"\\u003e \\u003ccaption language=\\\"En\\\"\\u003e \\u003cdiv class=\\\"CaptionNumber\\\"\\u003eTable 4\\u003c/div\\u003e \\u003cdiv class=\\\"CaptionContent\\\"\\u003e \\u003cp\\u003eCorneal endothelial cell density and survival ratio\\u003c/p\\u003e \\u003c/div\\u003e \\u003c/caption\\u003e \\u003ccolgroup cols=\\\"5\\\"\\u003e \\u003cdiv align=\\\"left\\\" class=\\\"colspec\\\" colname=\\\"c1\\\" colnum=\\\"1\\\"\\u003e\\u003c/div\\u003e \\u003cdiv align=\\\"left\\\" class=\\\"colspec\\\" colname=\\\"c2\\\" colnum=\\\"2\\\"\\u003e\\u003c/div\\u003e \\u003cdiv align=\\\"left\\\" class=\\\"colspec\\\" colname=\\\"c3\\\" colnum=\\\"3\\\"\\u003e\\u003c/div\\u003e \\u003cdiv align=\\\"left\\\" class=\\\"colspec\\\" colname=\\\"c4\\\" colnum=\\\"4\\\"\\u003e\\u003c/div\\u003e \\u003cdiv align=\\\"left\\\" class=\\\"colspec\\\" colname=\\\"c5\\\" colnum=\\\"5\\\"\\u003e\\u003c/div\\u003e \\u003cthead\\u003e \\u003ctr\\u003e \\u003cth align=\\\"left\\\" colname=\\\"c1\\\"\\u003e\\u0026nbsp;\\u003c/th\\u003e \\u003cth align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003eTrab\\u003c/p\\u003e \\u003c/th\\u003e \\u003cth align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003eEXP\\u003c/p\\u003e \\u003c/th\\u003e \\u003cth align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003ep-value\\u003c/p\\u003e \\u003c/th\\u003e \\u003cth align=\\\"left\\\" colspan=\\\"1\\\" nameend=\\\"c5\\\" namest=\\\"c5\\\"\\u003e\\u0026nbsp;\\u003c/th\\u003e \\u003c/tr\\u003e \\u003c/thead\\u003e \\u003ctbody\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003ePreoperative CED, cells/mm\\u003csup\\u003e2\\u003c/sup\\u003e\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e2389\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;321\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e2111\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;510\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e0.0008\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colspan=\\\"1\\\" nameend=\\\"c5\\\" namest=\\\"c5\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003e12 mos CED, cells/mm\\u003csup\\u003e2\\u003c/sup\\u003e\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e2333\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;357\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e2048\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;548\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colspan=\\\"2\\\" nameend=\\\"c5\\\" namest=\\\"c4\\\"\\u003e \\u003cp\\u003e0.0011\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003e24 mos CED, cells/mm\\u003csup\\u003e2\\u003c/sup\\u003e\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e2284\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;394\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e1953\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;587\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colspan=\\\"2\\\" nameend=\\\"c5\\\" namest=\\\"c4\\\"\\u003e \\u003cp\\u003e0.0005\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003e36 mos CED, cells/mm\\u003csup\\u003e2\\u003c/sup\\u003e\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e2230\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;424\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e1845\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;628\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colspan=\\\"2\\\" nameend=\\\"c5\\\" namest=\\\"c4\\\"\\u003e \\u003cp\\u003e0.0002\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003e12 mos Survival ratio, %\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e97.5\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;7.4\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e95.3\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;15.8\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colspan=\\\"2\\\" nameend=\\\"c5\\\" namest=\\\"c4\\\"\\u003e \\u003cp\\u003e0.333\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003e24 mos Survival ratio, %\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e95.5\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;10.2\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e90.3\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;17.2\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colspan=\\\"2\\\" nameend=\\\"c5\\\" namest=\\\"c4\\\"\\u003e \\u003cp\\u003e0.0484\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003e36 mos Survival ratio, %\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e93.3\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;12.5\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e85.0\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;19.5\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colspan=\\\"2\\\" nameend=\\\"c5\\\" namest=\\\"c4\\\"\\u003e \\u003cp\\u003e0.0064\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003c/tbody\\u003e \\u003c/colgroup\\u003e \\u003ctfoot\\u003e \\u003ctr\\u003e\\u003ctd colspan=\\\"5\\\"\\u003eCED: endothelial corneal cells density\\u003c/td\\u003e\\u003c/tr\\u003e \\u003ctr\\u003e\\u003ctd colspan=\\\"5\\\"\\u003eTrab: trabeculectomy.\\u003c/td\\u003e\\u003c/tr\\u003e \\u003ctr\\u003e\\u003ctd colspan=\\\"5\\\"\\u003eEXP: Ex-Press surgery.\\u003c/td\\u003e\\u003c/tr\\u003e \\u003c/tfoot\\u003e \\u003c/table\\u003e\\u003c/div\\u003e \\u003c/p\\u003e\"},{\"header\":\"Discussion\",\"content\":\"\\u003cp\\u003eThe results of the is study demonstrated that Ex-Press surgery significantly decrease the IOP and the number of postoperative glaucoma medications in patients with glaucoma. After 3 years of follow-up, the mean postoperative IOP values were 11.3 mmHg in the POAG group and 11.6 mmHg in the PEX group. Regarding postoperative IOP, several studies of the results of EXP indicated that the patients' postoperative IOP was 13.2\\u0026ndash;14.7 mmHg after 3 years [\\u003cspan citationid=\\\"CR1\\\" class=\\\"CitationRef\\\"\\u003e1\\u003c/span\\u003e, \\u003cspan citationid=\\\"CR2\\\" class=\\\"CitationRef\\\"\\u003e2\\u003c/span\\u003e, \\u003cspan citationid=\\\"CR4\\\" class=\\\"CitationRef\\\"\\u003e4\\u003c/span\\u003e]. Our present patients' surgical outcomes included IOP values that are lower than those of the cited reports. One of the possible reasons for this discrepancy is that our patients' pre-operative IOP values were lower than those of the patients in the previous studies. Postoperative IOP values that are even lower than patient's low preoperative IOP values are needed. In the present study we excluded patients who underwent additional glaucoma surgery due to high postoperative IOP, and since we used data only from cases in which the surgery was successful, the postoperative IOP in our present patient series might be lower compared to those in earlier investigations.\\u003c/p\\u003e \\u003cp\\u003eIt is well known that glaucoma filtration surgery decreases the eye's CED. The mechanisms of CED reduction after EXP surgery might involve several factors, such as the effects of MMC, inflammation, and the abnormal aqueous humor flow [\\u003cspan additionalcitationids=\\\"CR10\\\" citationid=\\\"CR9\\\" class=\\\"CitationRef\\\"\\u003e9\\u003c/span\\u003e\\u0026ndash;\\u003cspan citationid=\\\"CR11\\\" class=\\\"CitationRef\\\"\\u003e11\\u003c/span\\u003e]. The mean CED survival ratio in the present POAG group was 93.3%, and that in the PEX group was significantly lower at 85.0%. In other words, the reduction ratio was 6.7% in the POAG group and 15.0% in the PEX group. The CED outcomes after Ex-Press surgery have been described; for example, Arimura et al. reported that at 2 years after Ex-Press surgery, the CED was decreased by 18.0% [\\u003cspan citationid=\\\"CR8\\\" class=\\\"CitationRef\\\"\\u003e8\\u003c/span\\u003e], and Omatsu et al. observed that at 2 years after Ex-Press surgery, the patients' CED had decreased by 2.5% [\\u003cspan citationid=\\\"CR7\\\" class=\\\"CitationRef\\\"\\u003e7\\u003c/span\\u003e]. A meta-analysis revealed that Ex-Press surgery the CED had decreased by 8.11% after 2 years [\\u003cspan citationid=\\\"CR5\\\" class=\\\"CitationRef\\\"\\u003e5\\u003c/span\\u003e]. One of the reasons for such a wide range of CED loss values in these studies (i.e., 2.5%, 8.11%, and 18.0%) is that both POAG and PEX patients were included in their analyses.\\u003c/p\\u003e \\u003cp\\u003eAoyama et al. reported that at 3 years after patients with POAG underwent Ex-Press surgery, their mean CED had decreased by 5.4% [\\u003cspan citationid=\\\"CR12\\\" class=\\\"CitationRef\\\"\\u003e12\\u003c/span\\u003e]. Our present finding is comparable. An investigation by Lee et al. indicated that Ex-Press surgery decreased the CED of POAG patients by 10.0% over a 12-month period [\\u003cspan citationid=\\\"CR6\\\" class=\\\"CitationRef\\\"\\u003e6\\u003c/span\\u003e]. Although that investigation was limited to POAG patients, the results differ somewhat from ours. In an earlier study by our research group, we compared the CED loss between cornea insertion and trabecular meshwork insertion and observed that the mean CED-reduction ratio was 5.2% in trabecular meshwork insertion group and 15.1% in the corneal insertion group [\\u003cspan citationid=\\\"CR13\\\" class=\\\"CitationRef\\\"\\u003e13\\u003c/span\\u003e]. There is also a report indicating that peripheral anterior synechia (PAS) formation causes CED loss [\\u003cspan citationid=\\\"CR14\\\" class=\\\"CitationRef\\\"\\u003e14\\u003c/span\\u003e]. It is thus apparent that the causes of CED reduction are influenced by various factors.\\u003c/p\\u003e \\u003cp\\u003eAs previous reports, the mean CED value fell significantly faster in the PEX group [\\u003cspan citationid=\\\"CR15\\\" class=\\\"CitationRef\\\"\\u003e15\\u003c/span\\u003e]. It is important to know how much Ex-Press surgery will reduce the CED of patients with pseudo-exfoliation glaucoma (PEX), which tends to reduce the CED even without Ex-Press surgery. Higashide et al. reported that at 2 years postsurgery, trabeculectomy decreased the CED by 4.8% in their POAG group and by 18.2% in their PEX group [\\u003cspan citationid=\\\"CR16\\\" class=\\\"CitationRef\\\"\\u003e16\\u003c/span\\u003e]. Although it is well known that PEX is a factor that reduces CED, the underlying causes are unknown. There was a report that cytokines are involved [\\u003cspan citationid=\\\"CR17\\\" class=\\\"CitationRef\\\"\\u003e17\\u003c/span\\u003e].\\u003c/p\\u003e \\u003cp\\u003eOur study has some limitations. We included patients who had undergone cataract surgery, TLO, or SLT [\\u003cspan additionalcitationids=\\\"CR19\\\" citationid=\\\"CR18\\\" class=\\\"CitationRef\\\"\\u003e18\\u003c/span\\u003e\\u0026ndash;\\u003cspan citationid=\\\"CR20\\\" class=\\\"CitationRef\\\"\\u003e20\\u003c/span\\u003e], and these surgeries affect the CED loss. Soro-Mart\\u0026iacute;nez et al. observed that trabeculectomy with simultaneous cataract surgery caused more endothelial cell damage than trabeculectomy alone [\\u003cspan citationid=\\\"CR21\\\" class=\\\"CitationRef\\\"\\u003e21\\u003c/span\\u003e]. We measured the present patients' CED only once at each timepoints. In addition, the measurement of the CED at the central cornea was not at exactly the same site in all cases, and measurement error is thus likely. It is desirable to measure the CED several times and use the average value. The number of patients in this study might also be too small to precisely evaluate the CED loss.\\u003c/p\\u003e \\u003cp\\u003eIn conclusion, Ex-Press surgery resulted in significantly lower IOP values and decreased the number of post-operative glaucoma medications for POAG and PEX patients similarly. The mean CED survival ratio was 93.3% in the patients with POAG and 85.0% in those with PEX. Ex-Press surgery decreased the CED significantly more quickly in the PEX patients compared to the POAG patients.\\u003c/p\\u003e\"},{\"header\":\"Declarations\",\"content\":\"\\u003cp\\u003e\\u003cstrong\\u003eCompliance with Ethical Standards\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eConflicts of interest:\\u0026nbsp;\\u003c/strong\\u003eThe authors declare that they have no conflicts of interest.\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eResearch involving human participants and/or animals:\\u003c/strong\\u003e All procedures were performed in accord with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards, and ethical approval for this research was obtained from the Institutional Review Board of the University of Toyama.\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eInformed consent:\\u003c/strong\\u003e Informed consent was obtained from all individual participants included in the study.\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eFunding:\\u003c/strong\\u003e No funding was received.\\u003c/p\\u003e\"},{\"header\":\"References\",\"content\":\"\\u003col\\u003e\\u003cli\\u003e\\u003cspan\\u003eSchultz SK, Iverson SM, Shi W, Greenfield DS. Safety and efficacy of achieving single-digit intraocular pressure targets with filtration surgery in eyes with progressive normal-tension glaucoma. J Glaucoma. 2016;25(2):217\\u0026ndash;22.\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003eGonzalez-Rodriguez JM, Trope GE, Drori-Wagschal L, Jinapriya D, Buys YM. Comparison of trabeculectomy versus Ex-PRESS: 3-year follow-up. Br J Ophthalmol. 2016;100(9):1269\\u0026ndash;73.\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003eArimura S, Takihara Y, Miyake S, Iwasaki K, Gozawa M, Matsumura T, et al. Randomized clinical trial for early postoperative complications of ex-press implantation versus trabeculectomy: Complications postoperatively of Ex-Press versus trabeculectomy Study (CPETS). Sci Rep. 2016;6:26080.\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003eNetland PA, Sarkisian SR, Jr., Moster MR, Ahmed, II, Condon G, Salim S, et al. Randomized, prospective, comparative trial of EX-Press glaucoma filtration device versus trabeculectomy (XVT study). Am J Ophthalmol. 2014;157(2):433\\u0026ndash;40 e3.\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003eChen G, Li W, Jiang F, Mao S, Tong Y. Ex-PRESS implantation versus trabeculectomy in open-angle glaucoma: A meta-analysis of randomized controlled clinical trials. PLOS ONE. 2014;9(1):e86045.\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003eLee GY, Lee CE, Lee KW, Seo S. Long-term efficacy and safety of ExPress implantation for treatment of open angle glaucoma. Int J Ophthalmol. 2017;10(9):1379\\u0026ndash;84.\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003eOmatsu S, Hirooka K, Nitta E, Ukegawa K. Changes in corneal endothelial cells after trabeculectomy and EX-PRESS shunt: 2-year follow-up. BMC Ophthalmol. 2018;18(1):243.\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003eArimura S, Miyake S, Iwasaki K, Gozawa M, Matsumura T, Takamura Y, et al. Randomised clinical trial for postoperative complications after Ex-PRESS implantation versus trabeculectomy with 2-year follow-up. Sci Rep. 2018;8(1):16168.\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003eStorr-Paulsen T, Norregaard JC, Ahmed S, Storr-Paulsen A. Corneal endothelial cell loss after mitomycin C-augmented trabeculectomy. J Glaucoma. 2008;17(8):654\\u0026ndash;7.\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003eMacdonald JM, Geroski DH, Edelhauser HF. Effect of inflammation on the corneal endothelial pump and barrier. Curr Eye Res. 1987;6(9):1125\\u0026ndash;32.\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003eMcDermott ML, Swendris RP, Shin DH, Juzych MS, Cowden JW. Corneal endothelial cell counts after Molteno implantation. Am J Ophthalmol. 1993;115(1):93\\u0026ndash;6.\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003eAoyama Y, Sakata R, Fujishiro T, Honjo M, Shirato S, Aihara M. Changes in corneal endothelial cell density after initial Ex-Press drainage device implantation and its relating factors over 3 years. Eye. 2023;37(1):69\\u0026ndash;74.\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003eOtsuka M, Tojo N, Hayashi A. Corneal endothelial cell loss after Ex-Press surgery depends on site of insertion, cornea or trabecular meshwork. Int Ophthalmol. 2023;43(10):3471\\u0026ndash;7.\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003eRowsey JJ, Gaylor JR. Intraocular lens disasters: Peripheral anterior synechia. Ophthalmology. 1980;87(7):646\\u0026ndash;64.\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003eHasegawa Y, Nejima R, Mori Y, Sakisaka T, Minami K, Miyata K, et al. Risk factors for corneal endothelial cell loss by cataract surgery in eyes with pseudoexfoliation syndrome. Clin Ophthalmol. 2016;10:1685\\u0026ndash;9.\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003eHigashide T, Nishino T, Sakaguchi K, Yamada Y, Sugiyama K. Determinants of corneal endothelial cell loss after trabeculectomy with mitomycin C. J Glaucoma. 2019;28(1):61\\u0026ndash;7.\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003eDjordjević-Jocić J, Zlatanovic G, Veselinovic D, Jovanovic P, Djordjevic V, Zvezdanovic L, et al. Transforming growth factor beta1, matrix-metalloproteinase-2 and its tissue inhibitor in patients with pseudoexfoliation glaucoma/syndrome. Vojnosanit Pregl. 2012;69(3):231\\u0026ndash;6.\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003eBourne RR, Minassian DC, Dart JK, Rosen P, Kaushal S, Wingate N. Effect of cataract surgery on the corneal endothelium: Modern phacoemulsification compared with extracapsular cataract surgery. Ophthalmology. 2004;111(4):679\\u0026ndash;85.\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003eKasahara M, Shoji N, Matsumura K. The influence of trabectome surgery on corneal endothelial cells. J Glaucoma. 2019;28(2):150\\u0026ndash;3.\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003eLeahy KE, Madigan MC, Sarris M, Watson SL, McCluskey P, White AJ. Investigation of corneal endothelial changes post selective laser trabeculoplasty. Clin Exp Ophthalmol. 2018;46(7):730\\u0026ndash;7.\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003eSoro-Martinez MI, Villegas-Perez MP, Sobrado-Calvo P, Ruiz-Gomez JM, Miralles de Imperial Mora-Figueroa J. Corneal endothelial cell loss after trabeculectomy or after phacoemulsification, IOL implantation and trabeculectomy in 1 or 2 steps. Graefes Arch Clin Exp Ophthalmol. 2010;248(2):249\\u0026ndash;56.\\u003c/span\\u003e\\u003c/li\\u003e\\u003c/ol\\u003e\"}],\"fulltextSource\":\"\",\"fullText\":\"\",\"funders\":[],\"hasAdminPriorityOnWorkflow\":false,\"hasManuscriptDocX\":true,\"hasOptedInToPreprint\":true,\"hasPassedJournalQc\":\"\",\"hasAnyPriority\":false,\"hideJournal\":false,\"highlight\":\"\",\"institution\":\"\",\"isAcceptedByJournal\":true,\"isAuthorSuppliedPdf\":false,\"isDeskRejected\":\"\",\"isHiddenFromSearch\":false,\"isInQc\":false,\"isInWorkflow\":false,\"isPdf\":false,\"isPdfUpToDate\":true,\"isWithdrawnOrRetracted\":false,\"journal\":{\"display\":true,\"email\":\"info@researchsquare.com\",\"identity\":\"international-ophthalmology\",\"isNatureJournal\":false,\"hasQc\":true,\"allowDirectSubmit\":false,\"externalIdentity\":\"inte\",\"sideBox\":\"Learn more about [International Ophthalmology](https://www.springer.com/journal/10792)\",\"snPcode\":\"10792\",\"submissionUrl\":\"https://submission.nature.com/new-submission/10792/3\",\"title\":\"International Ophthalmology\",\"twitterHandle\":\"\",\"acdcEnabled\":true,\"dfaEnabled\":true,\"editorialSystem\":\"em\",\"reportingPortfolio\":\"Springer Hybrid\",\"inReviewEnabled\":true,\"inReviewRevisionsEnabled\":false},\"keywords\":\"Ex-Press, glaucoma, corneal endothelial cell, primary open angle glaucoma, pseudo-exfoliation glaucoma\",\"lastPublishedDoi\":\"10.21203/rs.3.rs-4073890/v1\",\"lastPublishedDoiUrl\":\"https://doi.org/10.21203/rs.3.rs-4073890/v1\",\"license\":{\"name\":\"CC BY 4.0\",\"url\":\"https://creativecommons.org/licenses/by/4.0/\"},\"manuscriptAbstract\":\"\\u003ch2\\u003ePurpose\\u003c/h2\\u003e \\u003cp\\u003eWe compared corneal endothelial cell (CED) loss between primary open angle glaucoma (POAG) and pseudo-exfoliation glaucoma (PEX) after Ex-Press (EXP) surgery.\\u003c/p\\u003e\\u003ch2\\u003ePatients and Methods:\\u003c/h2\\u003e \\u003cp\\u003eThis was a single-facility retrospective study. We included patients who had undergone EXP surgery and were followed up \\u0026gt;\\u0026thinsp;3 years. We measured the CED before and after EXP surgery by noncontact specular microscopy. We measured the CED at baseline and 12, 24, and 36 months post-surgery and compared the means of the CED values and CED survival ratios after EXP surgery by paired t-test.\\u003c/p\\u003e\\u003ch2\\u003eResults\\u003c/h2\\u003e \\u003cp\\u003eWe included 119 eyes that underwent EXP surgery: POAG group, n\\u0026thinsp;=\\u0026thinsp;60 eyes; PEX group, n\\u0026thinsp;=\\u0026thinsp;59 eyes. In the POAG group, the mean CED decreased from 2389\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;321 at baseline to 2230\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;424 cells/mm\\u003csup\\u003e2\\u003c/sup\\u003e after 3 years. In the PEX group, the mean CED decreased from 2111\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;510 at baseline to 1845\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;628 cells/mm\\u003csup\\u003e2\\u003c/sup\\u003e after 3 years. After the 3-year follow-up, the CED survival ratio was 93.3\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;12.5% in the POAG group and significantly lower at 85.0\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;19.5% in the PEX group (p\\u0026thinsp;=\\u0026thinsp;0.0064). Two cases in the PEX group developed bullous keratopathy.\\u003c/p\\u003e\\u003ch2\\u003eConclusions\\u003c/h2\\u003e \\u003cp\\u003eCompared to POAG, EXP surgery for PEX patients decreased their corneal endothelial cells faster.\\u003c/p\\u003e\",\"manuscriptTitle\":\"Comparison of corneal endothelial cell density reduction between primary open angle glaucoma and pseudo-exfoliation glaucoma patients at 3 years after Ex-Press® surgery\",\"msid\":\"\",\"msnumber\":\"\",\"nonDraftVersions\":[{\"code\":1,\"date\":\"2024-03-13 19:09:09\",\"doi\":\"10.21203/rs.3.rs-4073890/v1\",\"editorialEvents\":[{\"type\":\"communityComments\",\"content\":0},{\"type\":\"decision\",\"content\":\"Revision requested\",\"date\":\"2024-05-02T03:37:28+00:00\",\"index\":\"\",\"fulltext\":\"\"},{\"type\":\"editorInvitedReview\",\"content\":\"\",\"date\":\"2024-04-28T18:05:48+00:00\",\"index\":\"hide\",\"fulltext\":\"\"},{\"type\":\"reviewerAgreed\",\"content\":\"68854255685757163668683526481040272786\",\"date\":\"2024-04-25T17:35:05+00:00\",\"index\":\"hide\",\"fulltext\":\"\"},{\"type\":\"reviewersInvited\",\"content\":\"\",\"date\":\"2024-04-25T02:42:49+00:00\",\"index\":\"\",\"fulltext\":\"\"},{\"type\":\"editorAssigned\",\"content\":\"\",\"date\":\"2024-03-12T09:54:32+00:00\",\"index\":\"\",\"fulltext\":\"\"},{\"type\":\"checksComplete\",\"content\":\"\",\"date\":\"2024-03-11T15:40:33+00:00\",\"index\":\"\",\"fulltext\":\"\"},{\"type\":\"submitted\",\"content\":\"International Ophthalmology\",\"date\":\"2024-03-11T11:09:27+00:00\",\"index\":\"\",\"fulltext\":\"\"}],\"status\":\"published\",\"journal\":{\"display\":true,\"email\":\"info@researchsquare.com\",\"identity\":\"international-ophthalmology\",\"isNatureJournal\":false,\"hasQc\":true,\"allowDirectSubmit\":false,\"externalIdentity\":\"inte\",\"sideBox\":\"Learn more about [International Ophthalmology](https://www.springer.com/journal/10792)\",\"snPcode\":\"10792\",\"submissionUrl\":\"https://submission.nature.com/new-submission/10792/3\",\"title\":\"International Ophthalmology\",\"twitterHandle\":\"\",\"acdcEnabled\":true,\"dfaEnabled\":true,\"editorialSystem\":\"em\",\"reportingPortfolio\":\"Springer Hybrid\",\"inReviewEnabled\":true,\"inReviewRevisionsEnabled\":false}}],\"origin\":\"\",\"ownerIdentity\":\"df560ba9-6260-4400-b8aa-41c981703c5e\",\"owner\":[],\"postedDate\":\"March 13th, 2024\",\"published\":true,\"recentEditorialEvents\":[],\"rejectedJournal\":[],\"revision\":\"\",\"amendment\":\"\",\"status\":\"published-in-journal\",\"subjectAreas\":[],\"tags\":[],\"updatedAt\":\"2024-08-01T17:07:03+00:00\",\"versionOfRecord\":{\"articleIdentity\":\"rs-4073890\",\"link\":\"https://doi.org/10.1007/s10792-024-03248-w\",\"journal\":{\"identity\":\"international-ophthalmology\",\"isVorOnly\":false,\"title\":\"International Ophthalmology\"},\"publishedOn\":\"2024-07-23 16:16:13\",\"publishedOnDateReadable\":\"July 23rd, 2024\"},\"versionCreatedAt\":\"2024-03-13 19:09:09\",\"video\":\"\",\"vorDoi\":\"10.1007/s10792-024-03248-w\",\"vorDoiUrl\":\"https://doi.org/10.1007/s10792-024-03248-w\",\"workflowStages\":[]},\"version\":\"v1\",\"identity\":\"rs-4073890\",\"journalConfig\":\"researchsquare\"},\"__N_SSP\":true},\"page\":\"/article/[identity]/[[...version]]\",\"query\":{\"redirect\":\"/article/rs-4073890\",\"identity\":\"rs-4073890\",\"version\":[\"v1\"]},\"buildId\":\"qtupq5eGEP_6zYnWcrvyt\",\"isFallback\":false,\"isExperimentalCompile\":false,\"dynamicIds\":[84888],\"gssp\":true,\"scriptLoader\":[]}","source_license":"CC-BY-4.0","license_restricted":false}