Wataru Kobayashi, MD,* Hiroshi Kunikata, MD, PhD,* Toshiaki Abe, MD, PhD,Þ and Toru Nakazawa, MD, PhD*

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ORIGINAL CLINICAL STUDY Retrospective Comparison of 25- and 23-Gauge Microincision Vitrectomy Surgery and 20-Gauge Vitrectomy for the Repair of Macular Hole Retinal Detachment Wataru Kobayashi, MD,* Hiroshi Kunikata, MD, PhD,* Toshiaki Abe, MD, PhD,Þ and Toru Nakazawa, MD, PhD* Purpose: To compare the anatomical and functional outcomes of 25- and 23-gauge microincision vitrectomy surgery (25G and 23G MIVS) instrumentation with the standard 20G pars plana vitrectomy (20G PPV) system in the treatment of primary macular hole retinal detachment (MHRD). Design: A retrospective comparative study. Methods: Forty-six eyes of 45 patients with MHRD underwent pars plana vitrectomy from March 1, 2006 to April 31, 2011. Fourteen, 13, and 19 eyes underwent 20G PPV, 23G MIVS, and 25G MIVS, respectively. The analysis included characteristics of the patients, single operation reattachment rate, final reattachment rate, closure rate of the macular hole, and rate of complications. The median follow-up period was 273 days. Results: Preoperative characteristics were similar in the 3 groups. The single operation success rate was 11 (79%) of 14 for 20G PPV, 10 (77%) of 13 for 23G MIVS, and 14 (74%) of 19 for 25G MIVS (P = 0.95). The closure rate of the macular hole was 9 (64%) of 14 for 20G PPV, 9 (69%) of 13 for 23G MIVS, and 11 (58%) of 19 for 25G MIVS (P = 0.78). One hundred percent of patients achieved final reattachment after multiple surgeries, excluding 2 patients who dropped out during the follow-up period. Rates of visual recovery and complications, including hypotony, were similar for all 3 procedures. Conclusions: The outcomes of 25G and 23G MIVS for the management of MHRD did not differ significantly from 20G PPV. Microincision vitrectomy surgery may be considered an alternative treatment, even for MHRD. Key Words: 25-gauge vitrectomy, 23-gauge vitrectomy, 20-gauge vitrectomy, macular hole retinal detachment, visual improvement (Asia Pac J Ophthalmol 2014;3: 331Y336) Macular hole retinal detachment (MHRD) is known as one of the most difficult diseases to treat surgically with complete success. 1Y3 If treatment does not succeed, MHRD can easily progress to total retinal detachment or proliferative vitreoretinopathy. Surgical intervention, particularly with vitrectomy, is therefore very important. Macular hole retinal detachment is thought to arise from the retinal conditions in myopic foveoschisis and posterior staphyloma. 4Y7 For this reason, eyes with foveoschisis From the *Department of Ophthalmology and Division of Clinical Cell Therapy, Tohoku University Graduate School of Medicine, Sendai, Japan. Received for publication May 14, 2013; accepted December 13, 2013. This article has been presented at ARVO in May 2012. The authors have no conflicts of interest to declare. Reprints: Hiroshi Kunikata, MD, PhD, Department of Ophthalmology, Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi, Aoba-ku, Sendai 980-8574, Japan. E-mail: kunikata@ oph.med.tohoku.ac.jp. Copyright * 2014 by Asia Pacific Academy of Ophthalmology ISSN: 2162-0989 DOI: 10.1097/APO.0000000000000031 should undergo vitrectomy with internal limiting membrane (ILM) peeling before MHRD occurs. 8Y11 However, as patients with these precursor conditions generally already have poor vision, it is difficult for them to notice the symptoms of foveoschisis, and thus they often come to eye clinics only after MHRD has already occurred. Development of the intraocular approach for MHRD began in the 1980s, and we are now finally able to perform vitrectomy with fluid-air exchange, gas injection, and ILM peeling 1,12Y17 with a high reattachment rate. In the past 10 years, 25G and 23G microincision vitrectomy surgery (MIVS) have become the 2 most popular gauges for MIVS, 18Y32 but a search of the PubMed system revealed no comparison of MIVS and 20-gauge pars plana vitrectomy (20G PPV) for MHRD, although there were many evaluations of 20G PPV alone. 14,16,17,33 We speculate that the reason MIVS has not been considered for MHRD treatment is that eyes with this condition often have a long axis or require intraocular tamponade agents. 16,17,33,34 Thus, the purpose of this report was to compare the structural and functional outcomes of using MIVS with 25G or 23G instrumentation and 20G PPV to treat primary MHRD. MATERIALS AND METHODS We retrospectively reviewed 46 eyes of 45 patients with MHRD who underwent 20G PPV, 23G MIVS, and 25G MIVS in Tohoku University Hospital from March 1, 2006 to April 31, 2011. The preoperative demographics of the patients are shown in Table 1. All of the surgeries were performed at the Surgical Retina Clinic of our hospital. The inclusion criterion was MHRD. The exclusion criteria were prior scleral buckling or vitrectomy, trauma, and complex vitreoretinal diseases such as proliferative vitreoretinopathy or giant retinal tear. After the purpose and procedures of the operation were explained, informed consent was obtained from all patients. This study conformed to the tenets of the Declaration of Helsinki and was approved by the institutional review board of Tohoku University Graduate School of Medicine. Twenty-gauge PPV was performed from March 2006 to December 2009. Twenty-three-gauge MIVS was performed from May 2008 to October 2010. Twenty-five-gauge MIVS was performed from September 2006 to April 2011. The choice of 20G PPV, 23G MIVS, and 25G MIVS depended on the surgeons preference. Vitreous surgery was performed by 1 of 5 surgeons at Tohoku University Hospital specializing in this procedure. Patients with phakic eyes underwent vitrectomy combined with cataract surgery, and patients with pseudophakic eyes underwent only vitrectomy. The median follow-up period was 273 days. Surgical Procedure All surgeries were performed under retrobulbar anesthesia using the oblique sclerotomy technique and were performed using the Accurus surgical system for vitrectomy and the Infiniti Ozil Asia-Pacific Journal of Ophthalmology & Volume 3, Number 6, November/December 2014 www.apjo.org 331

Kobayashi et al Asia-Pacific Journal of Ophthalmology & Volume 3, Number 6, November/December 2014 TABLE 1. Characteristics of Patients Characteristics 20G (n = 14) 23G (n = 13) 25G (n = 19) P Age, y 70.2 T 2.5 71.7 T 2.5 66.9 T 2.1 0.3329* Sex 0.4740 Male 1 3 4 Female 13 10 15 Laterality 0.4104 Right 9 9 9 Left 5 4 10 Refractive error, diopter j7.9 T 1.7 j9.5 T 1.7 j8.2 T 1.4 0.7733* Preoperative IOP, mm Hg 12.0 T 5.0 14.2 T 2.5 15.2 T 4.6 0.1023* Axial length, mm 27.5 T 3.6 (8 eyes) 28.8 T 4.5 (7 eyes) 27.1 T 2.6 (15 eyes) 0.5645* Hardness of nuclear cataract 0.5198 GEL 2 6 7 12 EL 3 2 2 1 Extent of retinal detachment 0.4559 Grade 1 3 6 8 Grade 2 5 3 5 Grade 3 6 4 6 Retinoschisis 3 5 1 0.0655 Preoperative BCVA, logmar 1.7 T 0.7 1.4 T 0.6 1.4 T 0.6 0.3512* *ANOVA. Pearson W 2 test. Kruskal-Wallis test. Vision System for cataract surgery (Alcon Laboratories, Fort Worth, Tex). First, an infusion cannula was inserted through the inferotemporal sclera followed by the insertion of 2 cannulas through superotemporal and superonasal sites, which were all kept closed until the vitrectomy began. Next, a corneal or scleral tunnel incision was made, followed by phacoemulsification, aspiration, and intraocular lens implantation, before the vitrectomy. After resecting the vitreal core, about 4 mg of triamcinolone acetonide (TA; Kenacort-A, Bristol-Meyers Squibb, Tokyo, Japan) was injected into the vitreous cavity to determine whether a posterior vitreous detachment (PVD) was present. If a PVD was not present, we created a PVD. After creating a PVD and removing peripheral residual gel, the ILM was removed in all cases. At a minimum, we attempted to remove the ILM from the area of the vascular arcade. According to their preference, the surgeons used TA, 0.125% indocyanine green (ICG; Santen Co, Osaka, Japan), or 0.25% ICG in ILM peeling, to improve visibility. After ILM peeling, we performed drainage of the subretina fluid through the macular hole, as gently and carefully as possible, without creating a retinotomy in the detached area. Finally, we injected sulfur hexafluoride (SF6), perfluoropropane (C3F8), or silicone oil (SO) in the eye and injected antibiotics and corticosteroids subconjunctivally. Twenty-Gauge Pars Plana Vitrectomy The conjunctiva was opened widely, and incisions were made perpendicularly to the sclera at 3.5- or 4-mm posterior to the limbus. All incisions were sutured at the end of the procedure with an absorbable suture. Twenty-Three-Gauge and 25G Microincision Vitrectomy Surgery The cannulas were inserted into the sclera using the oblique sclerotomy technique. The sclera was penetrated by a trocar 3.5 or 4 mm posterior to the limbus depending on the lens status. Almost none of the eyes that had 25G MIVS needed a suture, but if any significant leakage was noted, particularly for 23G MIVS, an absorbable suture was applied to close the scleral wound. Measurements of Clinical Findings At least 6 months after surgery, we reviewed clinical charts from the 20G, 23G, and 25G groups. We analyzed data including age, patients sex, laterality of the procedure, refractive error, preoperative intraocular pressure (IOP), preoperative and postoperative decimal best-corrected visual acuity (BCVA), hardness of nuclear cataract, extent of retinal detachment, presence of retinoschisis, intraoperative tamponade substance, rate of first reattachment, rate of final reattachment, rate of macular hole closure, and intraoperative and postoperative complications. Intraocular pressure was also measured 1 day, 1 week, 1 month, and 6 months postoperatively. The hardness of the nuclear cataract was determined with Emery-Little classification (EL). The extent of the retinal detachment was determined with a grade scale (grade 1: only postpole retinal detachment, within the vascular arcade; grade 2: retinal detachment over the entire vascular arcade [more than grade 1 and less than grade 3]; grade 3: total retinal detachment). We determined the presence of retinoschisis and macular hole closure with a slit-lamp examination or OCT (Zeiss- Humphrey model OCT-3000, Dublin, Calif). First reattachment was defined as complete reattachment of the retina during the initial period following surgery, after the gas in the eye had disappeared or the SO had been removed. Final reattachment was defined as complete reattachment 6 months after initial surgery and a lack of intraocular tamponade. In cases where first reattachment was not achieved, we obtained informed consent and performed additional vitreous surgery. Statistical Analyses A standard Japanese Landolt visual acuity chart provided the determination of decimal BCVA. Decimal values for BCVA 332 www.apjo.org * 2014 Asia Pacific Academy of Ophthalmology

Asia-Pacific Journal of Ophthalmology & Volume 3, Number 6, November/December 2014 Vitrectomy for Macular Hole Retinal Detachment were converted to logarithm of the minimal angle resolution (logmar) units for statistical analysis. Pearson W 2 test was used for intergroup comparisons of patients sex, laterality of MHRD, presence of retinoschisis, rate of combined vitrectomy and cataract surgery, tamponade substances, rate of macular hole closure, rate of first reattachment, rate of final reattachment, rate of postoperative visual improvement, and incidence of complications. Kruskal-Wallis test was used for intergroup comparisons of hardness of nuclear cataract and range of retinal detachment. An analysis of variance (ANOVA) was used for intergroup comparisons of patients age, refractive error, preoperative IOP, axial length, preoperative and postoperative BCVA, and surgical time. Wilcoxon signed rank test was used for intergroup comparisons of difference in preoperative and postoperative visual acuity. P G 0.05 was considered to be statistically significant. Statistical analysis was carried out using JMP Pro version 9.0.2 for Windows (SAS Institute, Tokyo, Japan). RESULTS A summary of the preoperative clinical data is shown in Table 1. The total number of patients who underwent vitrectomy for MHRD was 45 (46 eyes). We used the 20G system in 14 eyes, the 23G system in 13 eyes, and the 25G system in 19 eyes. We did not switch MIVS to 20G PPV instrumentation intraoperatively in any of the cases. There were no significant differences between the 3 groups in baseline characteristics. A summary of the intraoperative and postoperative data is shown in Table 2. There were no significant differences in the rate of combined cataract surgery or surgical time in the 3 surgical groups (P =0.75andP = 0.28, respectively). In MIVS cases needing SO, it was gently injected through an MIVS cannula using a 24G IV catheter (Surflo; Terumo Co, Tokyo, Japan). There was no significant difference in the tamponade substance used in the operation in the 3 groups (P = 0.45). In addition, there was no significant difference in the adjuvant used in the operation (P = 0.34). There were also no significant differences in the postoperative BCVA or visual improvement (90.2 logmar) (P = 0.24 and P = 0.73, respectively). There was no significant difference in preoperative and postoperative visual acuity between the 20G and 23G groups. However, there was a significant difference between preoperative and postoperative visual acuity in the 25G group (Fig. 1, P = 0.01). Finally, there were no significant differences in the macular hole closure rate, the rate of initial reattachment, or the rate of final reattachment (P =0.78,P = 0.95, and P = 0.07, respectively). Two patients in the 23G group declined further procedures for personal reasons. We were therefore unable to perform additional vitrectomies, and the patients did not achieve final reattachment. A comparison of surgical complications in the 3 groups is shown in Table 3. There were no cases of endophthalmitis, peripheral retinal break, or insufficient wound closure after any of the 3 procedures. Although there were several eyes with severe hypotony (G6 mm Hg) after each type of procedure, the difference in severe hypotony 1 day and 1 week after each type of operation was not significant (P = 0.64 and P = 0.47, respectively). Similarly, there were several eyes with elevated IOP (930 mm Hg) after all 3 procedures, but the difference between the 3 groups was not significant 1 day, 1 week, 1 month, or 6 months after the operation (P = 0.60, P = 0.23, P = 0.96, and P = 0.48, respectively). Although there was postoperative hypotony in 1 eye after 20G PPV and 4 eyes after MIVS, we did not observe leakage in any of the 5 eyes during our initial examination on the day after surgery. DISCUSSION There were no significant differences in the primary or final reattachment rate or closure rate of the macular hole in the 25G MIVS, 23G MIVS, and 20G PPV groups. These groups TABLE 2. Comparison of Surgical Procedures and Results in the 3 Groups Characteristics 20G (n = 14) 23G (n = 13) 25G (n = 19) P Procedure 0.7480* Without cataract surgery 6 4 6 With cataract surgery 8 9 13 Surgical time, min 85.8 T 30.3 60.8 T 21.4 71.1 T 49.0 0.2832 Tamponade substance 0.4456* SF6 2 3 8 C3F8 10 9 10 SO 2 1 1 Intraoperative adjuvant 0.3351* ICG 0.125% 2 3 0 ICG 0.25% 1 0 0 TA 1 3 3 ICG 0.25% and TA 7 6 13 Unknown 3 1 3 Postoperative status of macular hole 0.7817* Closed 9/14 (64%) 9/13 (69%) 11/19 (58%) Initial reattachment 11/14 (79%) 10/13 (77%) 14/19 (74%) 0.9452* Final reattachment 14/14 (100%) 11/13 (85%) 19/19 (100%) 0.0704* Postoperative BCVA, logmar 1.4 T 0.6 1.2 T 0.5 1.1 T 0.6 0.2394 Postoperative visual improvement (90.2 logmar) 7/14 (50%) 7/13 (54%) 12/19 (63%) 0.7332* ANOVA. *Pearson W 2 test. SF6 indicates sulfur hexafluoride. * 2014 Asia Pacific Academy of Ophthalmology www.apjo.org 333

Kobayashi et al Asia-Pacific Journal of Ophthalmology & Volume 3, Number 6, November/December 2014 FIGURE 1. Comparison of preoperative and postoperative best-corrected visual acuity (BCVA) in the 20G, 23G, and 25G groups. There was no significant difference in preoperative and postoperative BCVA between the 20G and 23G groups. However, there was a significant difference between preoperative and postoperative BCVA in the 25G group (P = 0.01, Wilcoxon signed rank test). had no significant differences in preoperative or intraoperative characteristics. There were no significant differences in postoperative hypotony or elevated IOP in the 3 groups, nor were there any postoperative complications, such as endophthalmitis, peripheral retinal break, or insufficient wound closure. Promisingly, 6 months postoperatively, we noted a significant improvement in BCVA in the 25G MIVS group, which we did not observe in the 23G MIVS and 20G PPV groups. Our study, which included results covering a period of 5 years, reinforced data showing that MHRD is most common in the Asian region. A PubMed search did not reveal any reports on surgery for MHRD in which a single hospital from outside Asia saw over 40 cases. 35Y37 The very high percentage of female patients in our study (83%) also reinforced reports that MHRD occurs most often in female patients. 3,16,36 Our results also matched previous reports showing that 20G PPV s initial reattachment rate is approximately 70%, 15,38Y40 its final reattachment rate is near 100%, 14,17,38 and that its closure rate for macular hole is approximately 60% to 70%. 15,41 All of these rates were comparable with the results we obtained with MIVS, although different studies have shown closure rates when using ILM peeling for MHRD ranging from low 36,38,39 to high. 17 Overall, our subjects did not show marked visual improvement, possibly because of the interval before surgery, or the adjunctive dye or steroid used intraoperatively, which might have affected postoperative visual improvement. This lack of visual improvement was also noted in earlier reports. 15,33 Postoperative hypotony, sometimes leading to endophthalmitis, has been reported with 25G MIVS, especially when straight incisions are used and the patients are younger. 42,43 We also had cases of hypotony after 25G and 23G MIVS in our study, as in previous reports, 44,45 but it was no more prevalent than after 20G PPV. The exact reason for the hypotony in these 5 eyes is unclear, as we did not observe leakage in any of the 4 eyes that had undergone MIVS during our initial examination on the day after surgery. We speculate, however, that some leakage may have occurred in the first hours after surgery that resolved before the initial examination. In the single case of hypotony among the eyes that underwent 20G PPV, we believe that the cause may have been TABLE 3. Comparison of Postoperative Complications in the 3 Groups Postoperative Complications 20G (n = 14) 23G (n = 13) 25G (n = 19) P Endophthalmitis 0 0 0 Peripheral retinal break 0 0 0 Insufficient wound closure 0 0 0 Severe hypotony (G6 mm Hg) 1 d Postoperative 1 (n = 13) 1 (n = 12) 3 (n = 17) 0.6375* 1 wk Postoperative 0 (n = 13) 0 (n = 12) 1 (n = 17) 0.4708* 1 mo Postoperative 0 0 0 6 mo Postoperative 0 0 0 Elevated IOP (930 mm Hg) 1 d Postoperative 1 (n = 13) 2 (n = 12) 1 (n = 17) 0.5997* 1 wk Postoperative 1 (n = 13) 2 (n = 12) 0 (n = 17) 0.2282* 1 mo Postoperative 1 1 1 0.9572* 6 mo Postoperative 0 0 1 0.4837* *Pearson W 2 test. 334 www.apjo.org * 2014 Asia Pacific Academy of Ophthalmology

Asia-Pacific Journal of Ophthalmology & Volume 3, Number 6, November/December 2014 Vitrectomy for Macular Hole Retinal Detachment ciliary body dysfunction. Finally, the incidence of postoperative elevated IOP was not significantly different in the 3 groups in our study, contradicting a previous report showing that the incidence of elevated IOP differed in MIVS and 20G PPV. 46 Even now, many surgeons select 20G PPV for MHRD, because this disease sometimes requires the use of ocular tamponades, such as SO, and because it is characterized by a long ocular axis (increasing the technical difficulty of performing PPV, due to the longer distance from the sclerotomy site to the posterior retina). For these reasons, MIVS, with its short and slender shaft, might generally be considered a difficult choice for MHRD surgery. In practice, however, we had no technical difficulties performing vitrectomy or ILM peeling with MIVS. In this study, we were able to inject SO with a 24G soft catheter inserted through the MIVS cannula. However, recent technical developments allowed us to easily inject SO even with the most popular gauge used in vitrectomy, that is, 25G. Although there are recent comparative studies on the use of 25G, 23G, and 20G vitrectomy for epiretinal membrane and rhegmatogenous retinal detachment, 47,48 this is the first report comparing the outcomes of 23G or 25G MIVS and 20G PPV for the repair of MHRD. Interestingly, our data show that significant visual improvement was achieved only in the 25G group, not in the 23G or 20G groups, despite the patients having similar clinical characteristics and undergoing similar procedures. The reason is unclear. The high rate of cataract surgery and absence of only ICG use in our 25G procedure may have contributed to postoperative visual recovery, although there were no other significant differences on these in the 3 groups. The improvement in vision may also have been because of the other reported advantages of 25G MIVS over 20G PPV, such as reduced surgical time, reduced postoperative astigmatism, and quickened visual recovery time. 29Y32 Therefore, we believe that there could be the visual improvement at 6 months in the 25G group, that is, the one using the smallest MIVS gauge, because of the less invasive nature of 25G MIVS. Although our study was limited by being retrospective and having a short follow-up period (6 months), we believe that MIVS may be considered an alternative approach to 20G PPV for the treatment of patients with MHRD, capable of maintaining the highest quality of postoperative vision. Further large clinical investigation may therefore be needed to evaluate postoperative visual quality and complications to determine the efficacy of this procedure for MHRD. 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