| | Microincision Vitrectomy Surgery and Intravitreal Bevacizumab as a Surgical Adjunct to Treat Diabetic Traction Retinal DetachmentReceived 6 June 2008; received in revised form 4 November 2008; accepted 4 November 2008. published online 09 March 2009. PurposeTo investigate the feasibility and efficacy of microincision vitrectomy surgery (MIVS) combined with intravitreal bevacizumab (IVB) as a surgical adjunct for treating traction retinal detachment (TRD) secondary to severe proliferative diabetic retinopathy (PDR). DesignRetrospective, comparative, consecutive, interventional case series. ParticipantsSeventy-one eyes of 59 consecutive patients who underwent primary vitrectomy for diabetic TRD and were followed up for more than 6 months after surgery. MethodsEyes that received IVB (1 mg) as a preoperative adjunct followed by MIVS (IVB/MIVS group) from November 2005 through December 2007 were compared with eyes that underwent conventional 20-gauge pars plana vitrectomy (20-g PPV group) from September 2003 through October 2005. Main Outcome MeasuresPrimary and ultimate anatomic success, intraoperative and postoperative complications, and final visual success with at least 6 months of follow-up. ResultsThis series included 38 eyes (33 patients) in the IVB/MIVS group and 33 eyes (26 patients) in the 20-g PPV group. The primary and ultimate anatomic success rates (95% vs. 91% and 100% in both groups, respectively) and the mean visual acuity changes did not differ significantly between groups; the surgical time and intraoperative bleeding in the IVB/MIVS group decreased significantly compared with the 20-g PPV group (P<0.001). The rate of visual improvement of 3 lines or more at the 6-month follow-up was 68% in the IVB/MIVS group and 49% in the 20-g PPV group, respectively. Progression of the preexisting TRD after IVB occurred in 7 eyes (18%). Absence of previous laser photocoagulation (P = 0.025) and the presence of a ring-shaped fibrovascular membrane (P = 0.013) were relevant findings in eyes with these IVB-induced complications. ConclusionsIntravitreal bevacizumab plus MIVS offers comparable anatomic success compared with conventional 20-gauge PPV in patients with TRD resulting from severe PDR. This technique shortens the surgical time with fewer intraoperative complications and favorable visual recovery. However, caution should be taken because of rapid progression of the preexisting TRD after IVB in some patients. Financial Disclosure(s)The author(s) have no proprietary or commercial interest in any materials discussed in this article. Available online: March 9, 2009. Tractional retinal detachment (TRD) is a serious complication of severe proliferative diabetic retinopathy (PDR). Conventional 20-gauge pars plana vitrectomy (PPV) is the standard treatment of choice for PDR and achieves good anatomic success.1, 2, 3, 4, 5 However, surgically induced complications, that is, intraoperative bleeding and iatrogenic retinal breaks, recurrent or persistent vitreous hemorrhage, or both, retinal redetachment, postoperative reproliferation, anterior hyaloid fibrovascular proliferation, and development of neovascular glaucoma (NVG) are major concerns in diabetic vitrectomy,6, 7, 8, 9, 10, 11 sometimes resulting in poor anatomic and serious long-term visual impairment.12, 13 Recent advances in surgical and medical retina treatment, that is, microincision vitrectomy surgery (MIVS) and intravitreal injection of drugs targeting vascular endothelial growth factor (VEGF), are impressive options for treating a variety of vitreoretinal diseases. This trend toward less invasive therapy led the authors to evaluate the synergistic effect of combining the 2 approaches to treat complications of severe PDR. Transconjunctival MIVS with 25- or 23-gauge instrumentation has several advantages over traditional 20-gauge vitrectomy.14, 15, 16, 17, 18, 19 Smaller incisions without peritomy and self-sealing sclerotomy may decrease trauma with faster wound healing, may diminish conjunctival scarring and patient discomfort, and may decrease postoperative inflammation and induced astigmatism, theoretically facilitating early visual recovery in macular diseases.20, 21, 22, 23 Although MIVS initially was recommended for macular pathologic features or simple vitreous hemorrhage because of the limited designs and fragility of small-gauge instrumentation in the initial stage, recent development of rigid instrumentation and a bright light source expanded the indications for MIVS to include complex vitreoretinal disorders such as rhegmatogenous retinal detachment (RRD) and proliferative vitreoretinal disorders.16, 18, 19, 24, 25 Transconjunctival MIVS should be more suitable than traditional 20-gauge PPV for treating severe PDR because the conjunctiva-preserving nature of MIVS allows repeated vitrectomy or filtering surgery that may be needed in patients with diabetes complicated with NVG even after vitrectomy. Less postoperative inflammation associated with MIVS may facilitate early visual recovery in PDR as well as in macular diseases. However, it still remains a concern whether complex intraocular manipulations such as fibrovascular membrane dissection and hemostasis in diabetic vitrectomy can be managed steadily using small-gauge instrumentation. Intraocular neovascularization in patients with diabetes is correlated with retinal ischemia, which stimulates VEGF, a key molecule responsible for ocular neovascularization.26, 27 Direct targeting of VEGF with anti-VEGF pharmacotherapy is another therapeutic option for intraocular neovascularization.28, 29 Bevacizumab (Avastin; Genentech, Inc., South San Francisco, CA), a full-length humanized monoclonal antibody that binds all VEGF isoforms, was approved by the Food and Drug Administration for treating metastatic colorectal cancer.30 Recent studies of off-label intravitreal bevacizumab (IVB) injections have reported the efficacy and safety of bevacizumab for preventing intraocular bleeding and postoperative complications in standard 20-gauge vitrectomy or filtering surgery.31, 32, 33, 34, 35 Therefore, IVB as a surgical adjunct to MIVS is expected to reduce concerns about intraoperative bleeding and to encourage the use of MIVS for complications associated with severe PDR. Adjunctive IVB was used to suppress intraocular neovascularization followed by MIVS in consecutive patients with TRD secondary to severe PDR. The purpose of this study was to evaluate retrospectively the feasibility and outcomes of this approach compared with traditional 20-gauge vitrectomy without preoperative IVB. Patients and Methods  Inclusion and Exclusion Criteria This retrospective chart review included a consecutive series of patients with diabetes who underwent primary PPV for TRD secondary to PDR between September 2003 and December 2007 at Osaka University Medical School Hospital or Kagawa University Hospital. The institutional review boards of both facilities approved the study. Patients provided written informed consent after they received a detailed description of the surgical procedure. The study adhered to the tenets of the Declaration of Helsinki. Patients had not undergone previous vitreoretinal surgery except laser photocoagulation to treat PDR or clinically relevant diabetic macular edema. The indications for PPV included a TRD involving the macula, combined TRD and RRD, or extramacular TRD with an adherent fibrovascular membrane causing excessive macular traction. The macular status and the extent of the TRD were confirmed by B-scan echography in patients with a preretinal hemorrhage that obscured clear fundus visualization. Patients were excluded if they had a TRD for more than 1 year and a best-corrected visual acuity of less than hand movements, an extramacular TRD without macular traction, or less than 6 months of follow-up after the initial surgery. Surgical Technique From September 2003 through October 2005, PPV was performed using a standard 20-gauge 3-port system (20-gauge PPV group). After conjunctival peritomy, sclerotomies were introduced using a 20-gauge microvitreoretinal blade. Core vitrectomy using a high-speed vitreous cutter (2500 cycles/minute) was performed with intravitreal injection of triamcinolone acetonide to visualize the vitreous gel and to identify the location of vitreoretinal adhesions. Peripheral vitrectomy was performed to relieve anterior posterior traction. Fibrovascular membrane dissection and segmentation were performed to remove all tangential traction using a magnifying prismatic lens. Delamination techniques also removed as much fibrovascular tissue as possible with vitreoretinal scissors, forceps, and a tissue manipulator. Vitreous base shaving (360°) under scleral depression was performed to remove peripheral cortical gel and release epicenters of anterior fibrovascular proliferation. Endolaser photocoagulation was applied to complete panretinal photocoagulation up to the anterior retina. Any retinal breaks also were treated. In pseudophakic eyes, posterior capsulectomies were created using the vitreous cutter to improve intraocular visualization if needed. Phacoemulsification and aspiration were performed simultaneously through a 3.0-mm sclerocorneal wound in patients with cataract. An acrylic foldable intraocular lens (IOL) was placed in the capsular bag in patients with an intact capsule. Fluid–gas exchange was performed for retinal breaks, RRD, or both, by flushing with 50 ml of a premixed nonexpansile concentration of 20% sulfur hexafluoride or 14% perfluoropropane. In patients with severe visual impairment in the fellow eye, silicone oil tamponade was considered. After surgery, all sclerotomies and conjunctival incisions were sutured and steroid was injected subconjunctivally. Topical antibiotic ointment was applied, and the eye was patched and shielded. Patients who had undergone fluid–gas exchange were instructed to remain face down for 7 to 10 days. From November 2005 through December 2007, diabetic TRD was treated by MIVS after adjunctive pretreatment with IVB administered (IVB/MIVS group) using strict aseptic techniques.36 A 50-μl aliquot of commercially available bevacizumab (25 mg/ml) was prepared and placed in a tuberculin syringe with a 29-gauge needle and was refrigerated until use. Bevacizumab (1 mg) was injected intravitreally via the pars plana. In patients with increased IOP, a paracentesis (100–200 μl) was created to normalize the IOP. Patients were instructed to use topical levofloxacin or gatifloxacin and were reexamined on days 1, 3, and every week after injection. During the follow-up visit, visual acuity (VA) and IOP measurements were obtained and slit-lamp microscopy and fundus microscopy were performed. If patients had media opacities that obscured the fundus, the extent and progression of the TRD were evaluated by B-scan echography. Microincision vitrectomy surgery was performed using either a 25- or 23-gauge trocar or cannula system (Alcon Laboratories, Inc., Fort Worth, TX; Dutch Ophthalmic Research Center, Zuidland, The Netherlands) by no more than 1 month after IVB pretreatment. Surgeon preference determined the gauge without randomization; the standard MIVS procedures have been described previously.15, 16, 17, 18, 19 The trocar and cannula device was inserted using the 2-step entry method developed by Eckardt.17 After oblique insertion at approximately a 30° to 45° angle to the sclera of a 25- or 23-gauge microvitreoretinal blade through the conjunctiva and sclera after conjunctival displacement to misalign the conjunctiva and sclera incisions, blunt trocars for transscleral cannulas were inserted through the pars plana in the supranasal, supertemporal, and inferotemporal quadrants for infusion and insertion of intraocular instruments. To overcome the limitations and fragility of small-gauge instrumentation, several surgical techniques and devices have been modified and developed. In contrast to the halogen illumination commonly used for traditional 20-gauge PPV, a xenon or mercury vapor light source is used in MIVS to obtain bright endoillumination and clear visualization.37, 38 The surgical techniques for removing fibrovascular membranes during MIVS differ from those in traditional 20-gauge surgery; that is, the membranes are cut and removed using a small-gauge high-speed vitrectomy cutter instead of vitreoretinal scissors (see Video 1, available at http://aaojournal.org). When fibrovascular membranes extensively adhered to the detached retina, a bimanual technique using a membrane forceps and a vitrectomy cutter was performed using a 25- or 27-gauge self-retaining chandelier illumination fiber37, 38 (see Video 2, available at http://aaojournal.org). A peripheral vitrectomy and vitreous base shaving were performed under a wide-angle viewing system instead of scleral depression.39, 40 Endolaser photocoagulation up to the anterior retina was applied using an extendable laser probe. To preserve the conjunctiva during MIVS, phacoemulsification and IOL implantation were performed through a 3-mm clear corneal incision, and a sutureless contact lens ring was used during vitrectomy.19 At the end of surgery, the IOP was decreased to identify rebleeding from vascular epicenters, and endoillumination with gentle scleral indentation helped to identify peripheral retinal pathologic features. After removing the supertemporal and supranasal cannulas with the infusion clamped, the clamp–unclamp infusion technique was performed,11 and the sclerotomies were inspected for fluid leaks. The inferotemporal cannula and infusion line were removed en bloc with the infusion unclamped followed by conjunctival repositioning and inspection. If the vitreous cavity was filled with air or long-acting gas at the end of surgery, air-tightness was confirmed by pouring balanced salt solution (Alcon Laboratories, Inc.) around the wounds to check air bubbling through the sclerotomy. If a bleb leak was found, transconjunctival sutures were placed to close the leaky sclerotomy. The other procedures were the same as the traditional 20-gauge procedures described previously. Data Analysis The patient medical records and surgical notes were reviewed for age; gender; follow-up; lens status; previous treatments; TRD type; coexisting complications; systemic data including serum creatinine levels and hemoglobin A1c levels; preoperative best-corrected visual acuity; postoperative best-corrected VA at the 6-month follow-up visit; preoperative and postoperative IOP at the 1-day, 1-week, and 6-month follow-up visits; operating time; anatomic success rate; and intraoperative and postoperative complications. Instrumentation used to dissect and remove fibrovascular membranes, and the strategies for intraoperative hemostasis were recorded by reviewing the surgical video and summary sheets. The severity of intraoperative bleeding was graded based on the methodology for achieving hemostasis, with 0 indicating self-limited bleeding without hemostatic procedures; 1 indicating intraoperative hemostasis via gentle, direct depression of the bleeding point with the blunt tip of a vitreous cutter; 2 indicating hemostasis with elevated IOP; and 3 indicating hemostasis with elevated IOP and cautery of the bleeding point. In patients who underwent adjunctive IVB pretreatment and MIVS, the efficacy and complications of IVB, requirement for conversion to 20-gauge instrumentation during surgery, and the rate of self-sealing also were reviewed. Postoperative hypotony was defined as an IOP of 7 mmHg or less. The VA was measured using the Landolt C acuity chart and was analyzed on a logarithm of minimal angle of resolution (logMAR) scale. Counting fingers vision was defined as 0.01 (2.0 logMAR) and hand movements was defined as 0.001 (3.0 logMAR).41 Visual improvement was defined as an increase of at least 0.3 logMAR unit. Where appropriate, the Mann–Whitney rank-sum test, the Student t test, and the Fisher exact test were used to compare the differences in the groups. Statistical analysis was performed using SPSS software version 10.0J (SSPS, Inc., Chicago, IL). P≤0.05 was considered to be statistically significant. Results A total of 71 eyes of 59 patients (38 eyes in the IVB/MIVS group and 33 eyes in the 20-gauge PPV group) met the study criteria. The patient demographics and preoperative ocular findings for the 2 groups are listed in Table 1. Although both eyes of 5 patients in the IVB/MIVS group and both eyes of 7 patients in the 20-gauge PPV group met the study criteria and were enrolled for data analysis, there were no significant differences in the baseline parameters between the groups, including age, bilaterality, preoperative VA, lens status, TRD type, preexisting complications, and major systemic data between the groups. The surgical results were compared for the 2 study intervals in which different procedures and instruments were used. The mean follow-up period of 17.5±13.3 months in the 20-gauge PPV group was substantially longer than the mean follow-up of 11.8±4.5 months in the IVB/MIVS group, but the difference did not reach significance (P = 0.43). Six-month follow-up data were available for every patient in both groups. | | |  | Parameters | Intravitreal Bevacizumab/Microincision Vitrectomy Surgery Group | 20-Gauge Pars Plana Vitrectomy Group | P Value | |
|---|
| No. eyes/patients | 38/33 | 33/26 | | | | No. men/women | 19/14 | 15/11 | 0.80 | | | Age (yrs) | | | | | |  Mean±SD | 50.3±14.0 | 54.5±10.9 | 0.22 | | | Range | 22–73 | 28–67 | | | | Bilaterality, no. (%) | 5(15) | 7(27) | 0.43 | | | Preoperative BCVA | | | | | | Mean (range) | 0.03(HM–0.7) | 0.05(HM–0.8) | | | | LogMAR±SD | 1.34±0.95 | 1.13±0.83 | 0.46 | | | IOP (mmHg) | | | | | | Mean±SD | 17.9±9.2 | 15.6±4.2 | 0.35 | | | Range | 8–55 | 8–31 | | | | Lens status | | | | | | Phakia/pseudophakia | 31/7 | 29/4 | 0.69 | | | Type of RD, no. (%) | | | | | | TRD only | 32(84) | 28(85) | 0.80 | | | Combined TRD/RRD | 6(16) | 5(15) | | | | Macula involved, no. (%) | 17(45) | 13(39) | 0.83 | | | PVD, no. (%) | | | | | | None | 12(32) | 12(36) | 0.86 | | | Incomplete | 26(68) | 21(64) | | | | Preoperative complication, no. (%) | | | | | | Persistent VH | 17(45) | 12(36) | 0.63 | | | INV or NVG | 5(13) | 6(18) | 0.80 | | | Previous PRP, no. (%) | | | | | | None | 8(21) | 6(18) | 0.99 | | | Incomplete | 30(79) | 27(82) | | | | Systemic data | | | | | | HbA1c (%)±SD | 7.7±1.9 | 7.3±1.1 | 0.72 | | | Creatinine (mg/dl)±SD | 1.4±1.6 | 1.2±0.8 | 0.87 | | | Follow-up (mos) | | | | | | Mean±SD | 11.8±4.5 | 17.5±13.3 | 0.43 | | | Range | 6–27 | 6–47 | | | | | |
Anatomic Success Rate and Visual Recovery The initial anatomic success rate was 95% in the IVB/MIVS group and 91% in the 20-gauge PPV group (Table 2). Although vitreoretinal reoperations were required for retinal reattachment, the final anatomic success rate was 100% in both groups. The VA levels in the 71 study eyes at baseline and 6 months after surgery are shown in Figure 1. The preoperative VA ranged from hand movements to 0.7 (mean, 0.03) in the IVB/MIVS group and from hand movements to 0.8 (mean, 0.05) in the 20-gauge PPV group. The mean postoperative VA was 0.30 in the IVB/MIVS group and 0.22 in the 20-gauge PPV group. The mean postoperative VA improved significantly compared with the mean preoperative VA in both groups (P<0.001). Despite no significant differences in the mean preoperative VA between the groups (P = 0.46), the difference in the mean VAs 6 months after surgery reached borderline significance (P = 0.047). However, the overall mean VA changes before and 6 months after surgery (logMAR units, −0.81±1.16 in the IVB/MIVS group vs. −0.47±0.92 in the 20-gauge PPV group) did not differ significantly between the groups (P = 0.18). Figure 2 shows that the VA at the 6-month follow-up improved by 3 lines or more in 26 eyes (68%), was unchanged in 8 eyes (21%), and decreased by 3 lines or more in 4 eyes (11%) in the IVB/MIVS group. In the 20-gauge PPV group, the VA improved in 16 eyes (49%), was unchanged in 13 eyes (39%), and decreased in 4 eyes (12%). Visual improvement in the IVB/MIVS group was higher than that in the 20-gauge PPV group, but the difference between groups did not reach to statistical significance (P = 0.14). Surgical Procedures and Intraoperative Complications The main surgical techniques during vitrectomy were similar for the 2 groups (Table 2). However, the surgical time for IVB/MIVS was significantly shorter (P<0.001) than for conventional 20-gauge PPV. The chance of using microforceps and microscissors to remove fibrovascular membranes during IVB/MIVS was significantly less than during conventional 20-gauge PPV (P = 0.02 and P<0.001, respectively). Despite extensive peripheral shaving in both groups, 28 eyes (74%) in the IVB/MIVS group had self-sealing sclerotomies without sutures. Conversion to 20-gauge instrumentation to complete surgery was unnecessary in the IVB/MIVS group. The intraoperative and postoperative complications in both groups are summarized in Table 3. Overall, the incidence of intraoperative iatrogenic retinal tears did not differ significantly between the groups (P = 0.11); however, the incidence in the 20-gauge PPV group (41%) was higher than that in the IVB/MIVS group (19%). Sclerotomy-related retinal tears occurred in 2 eyes (6%) in the 20-g PPV group. The other retinal breaks in both groups occurred during posterior manipulations including membrane removal. Iatrogenic tears were treated during surgery by endolaser photocoagulation, cryoretinopexy, or both and were unrelated to subsequent complications such as RRD. Hemorrhages during fibrovascular membrane manipulation occurred in all cases regardless of the use of conventional 20-gauge or small-gauge instruments. However, the severity of the intraoperative bleeding differed significantly (P<0.001) between the groups, suggesting that intraoperative bleeding in the conventional 20-gauge PPV group was more severe and that it was more difficult to achieve hemostasis than in the IVB/MIVS group. Ten (32%) of 31 phakic eyes in the IVB/MIVS group and 7 (24%) of 29 phakic eyes in the conventional 20-g PPV group underwent vitrectomy with crystalline lens sparing. No eyes had crystalline lens-related complications such as inadvertent instrument touch or secondary cataract formation. Postoperative Complications and Reoperation Rates The major postoperative complication was transient fibrin formation in the anterior chamber, vitreous cavity, or both in 9 eyes (24%) in the IVB/MIVS group and in 15 eyes (45%) in the 20-gauge PPV group. All fibrin formation resolved after postoperative topical steroid administration and did not affect vision. Postoperative vitreous hemorrhage developed in 5 eyes (13%) in the IVB/MIVS group and in 9 eyes (27%) in the 20-gauge PPV group. Of these, 1 eye (20%) in the IVB/MIVS group and 4 eyes (44%) in the 20-gauge PPV group underwent repeated vitrectomy, after which no eyes had recurrent postoperative vitreous hemorrhage during follow-up. Anterior hyaloid fibrovascular proliferation9 did not develop in any eyes throughout the follow-up period. Iris neovascularization (INV) and NVG are the most serious postoperative complications of vitreous surgery for severe PDR.10, 11 Although no new INV or NVG occurred during follow-up, preexisting INV and NVG were stabilized or controlled in only 2 (40%) of 5 eyes in the IVB/MIVS group and in 4 (67%) of 6 eyes in the 20-gauge PPV group after surgery. Despite the preoperative injection of bevacizumab in the IVB/MIVS group, control of the preexisting INV and NVG after surgery did not differ significantly between groups. Recurrent retinal detachment complicated by progressive fibrovascular proliferation developed in 2 eyes (5%) in the IVB/MIVS group and in 3 eyes (9%) in the 20-gauge PPV group, but the difference was not significant. An RRD developed in 1 eye (3%) in the 20-gauge PPV group. The causal retinal break was inferonasal but was not associated with sclerotomy-related complications. All 6 eyes underwent another vitrectomy and achieved retinal reattachment. Of the 2 eyes in the IVB/MIVS group, MIVS was repeated with 14% perfluoropropane gas tamponade. Although self-sealing sclerotomies were achieved in 28 eyes (74%) in the IVB/MIVS group, postoperative hypotony-related maculopathy occurred in 1 eye (3%) in the early study period of MIVS. Because a macular fold persisted even after the IOP returned to normal, repeated vitrectomy with internal limiting membrane peeling and air tamponade was performed and flattened the retinal fold successfully. Overall, in the IVB/MIVS group, vitreoretinal reoperations were the result of persistent vitreous hemorrhage (n = 1), recurrent retinal detachment (n = 2), and hypotony-related maculopathy (n = 1). In the 20-g PPV group, vitreoretinal reoperations were required because of persistent vitreous hemorrhage (n = 4), recurrent retinal detachment with progressive reproliferation (n = 3), and newly developed RRD after the initial surgery (n = 1). The reoperation rate did not differ significantly between the groups (P = 0.22). Rapid Progression of Tractional Retinal Detachment after Adjunctive Intravitreal Bevacizumab The mean interval between IVB and MIVS was 7.6 days (range, 2–30 days). No adverse systemic complications related to IVB occurred during follow-up. Rapid progression of the preexisting TRD occurred in 7 eyes (18%) after IVB. The patient demographics and baseline ocular characteristics with or without rapid progression of the TRD after IVB are shown in Table 4. There were no significant differences in the preoperative VA and IOP, TRD type, preexisting complications such as vitreous hemorrhage and INV/NVG, interval between IVB and MIVS, and major systemic data between eyes with or without rapid progression of TRD after IVB. Preoperative ring-shaped fibrovascular membrane formation (P = 0.013) and absence of previous panretinal photocoagulation (P = 0.025) were significant in eyes with rapidly progressive TRD. The final mean VA in eyes with progression of the preexisting TRD (0.15) was worse compared with eyes without this complication (0.5). | | | | Biologic and Environmental Factors | Progression of Preexisting Traction Retinal Detachment | P Value | |
|---|
| Yes (n = 7) | No (n = 31) | |
|---|
| Mean age±SD, yrs | 47.1±7.8 | 50.0±15.1 | 0.63 | | | Preoperative parameters | | | | | | BCVA (logMAR)±SD | 1.36±0.80 | 1.32±0.92 | 0.57 | | | IOP (mmHg)±SD | 16.1±5.7 | 18.4±9.9 | 0.42 | | | Absence of previous PRP, no. (%) | 4(57) | 4(13) | 0.025 | | | Combined TRD/RRD, no. (%) | 3(43) | 3(10) | 0.06 | | | INV/NVG, no. (%) | 0(0) | 5(16) | 0.56 | | | Ring-shaped FVM formation, no. (%) | 4(57) | 3(10) | 0.013 | | | VH, no. (%) | 2(29) | 15(48) | 0.39 | | | Interval between IVB and MIVS (days)±SD | 7.1±6.7 | 7.7±7.5 | 0.81 | | | Systemic data | | | | | | HbA1c (%)±SD | 7.6±1.2 | 7.7±12.0 | 0.81 | | | Creatinine (mg/dl)±SD | 1.0±0.3 | 1.5±1.8 | 0.87 | | | | |
Case Reports Case 1 A 46-year-old man with poorly controlled diabetes underwent bilateral panretinal photocoagulation. Despite extensive treatment, a prominent fibrovascular membrane developed in the left eye causing a macular TRD (Fig 3A). The VA in the left eye was 0.06. Bevacizumab (1 mg) was injected intravitreally in the left eye before MIVS. Four days later, the neovascular components in the fibrovascular membrane regressed with rapid fibrotic changes and reduction in the size of many abnormal new vessels (Fig 3B). Microincision vitrectomy surgery was uneventful with minimal intraoperative bleeding and easy membrane dissection using a 25-gauge vitrectomy (Fig 3C). Six months later, the VA improved to 0.15, and the macula was attached without reproliferation (Fig 3D). Case 2 A 48-year-old woman with insulin-dependent diabetes mellitus and no previous ocular treatment was referred to the authors. She had bilateral dense cataracts, rubeosis iridis, and a small pupil that obscured the fundus findings. However, large-caliber neovascular vessels comprising diffuse neovascularization elsewhere and a TRD with a large ring-shaped fibrovascular membrane were faintly visible in the left eye (Fig 4A). B-scan echography confirmed a shallow, extensive TRD (Fig 4B). The VA in the left eye was 0.02. Bevacizumab (1 mg) was injected intravitreally into the left eye to hasten regression of INV and retinal neovascularization and to prevent intraoperative bleeding. Four days later, despite INV regression, B-scan echography confirmed progression of the preexisting TRD (Fig 4C). The patient underwent uneventful MIVS, phacoemulsification, and IOL implantation using the 25-gauge system. A total retinal detachment with extensive contraction of the fibrotic membrane was observed during surgery (Fig 4D). The membrane was separated from the retinal surface and was dissected bimanually using membrane forceps and a 25-gauge vitrectomy with slight bleeding from the epicenters (Fig 4E). One month later, focal retinal redetachment with membrane reproliferation was treated successfully by repeated MIVS with the 25-gauge system. Six months later, the retina was reattached; the VA improved to 0.1 in the left eye at the final examination (Fig 4F). Discussion Microincision vitrectomy surgery combined with preoperative IVB can be beneficial for treating TRD secondary to severe PDR. The therapeutic efficacy is based on 2 surgical principles: eliminating intraoperative complications by pharmacologic involution of retinal neovascularization and simplifying the surgical technique with fewer instrument exchanges. However, the effect of bevacizumab, that is, less intraoperative bleeding, and the efficacy of small-gauge instrumentation are difficult to evaluate objectively, and the synergistic impact of combining the 2 has not been studied. In the current study, the baseline patient characteristics in the 2 groups did not differ significantly. Although the study eyes were recruited from 2 different study periods because of evolving innovations and refinements in the surgical system, the surgeries were conducted in consecutive patients in both groups. Therefore, the bias of case selection with different surgical procedures was eliminated. The primary retinal reattachment rates (95% vs. 91%) and ultimate reattachment rates evaluated at the final examination visit (100% in both group) did not differ between the groups, indicating that both techniques achieve favorable anatomic success in diabetic TRD. The differences in the surgical instruments used for fibrovascular membrane removal and the methodology for achieving hemostasis during surgery between the 2 groups were compared, and the results demonstrated that the chances of using vitreoretinal forceps and membrane scissors during the removal of the membrane in the MIVS group was significantly lower than in the 20-g PPV group (P = 0.02 and P<0.001, respectively). Because the 23- and 25-gauge vitrectomy ports are small and the distances from the ports to the tips are shorter than those of a conventional 20-gauge vitrectomy, the port of the small-gauge vitrectomy can be inserted readily between the fibrovascular membrane and retina, allowing successful membrane segmentation, dissection, and removal using a 23- or 25-gauge vitrectomy in most cases. In patients with combined TRD/RRD and extensively adhesive fibrovascular membranes, a bimanual technique consisting of use of a membrane forceps to grasp the membrane with 1 hand and a 23- or 25-gauge vitrectomy instead of scissors to separate the membrane from the retinal surface using the other hand can be performed easily. The membranes then can be removed using the vitrectomy without instrument exchanges. No eyes required conversion to the conventional 20-gauge vitrectomy technique for membrane removal. Use of a blunt membrane forceps and a vitrectomy for membrane separation and dissection may be safer than using conventional sharp 20-gauge instruments to prevent iatrogenic retinal breaks. This may account for the lower, although not significant (P = 0.11), incidence (19%) of iatrogenic breaks during membrane removal in the IVB/MIVS group compared with 41% in the 20-gauge PPV group. Intraoperative bleeding during removal of a fibrovascular membrane was observed in all cases whether conventional 20-gauge sharp instruments or small-gauge blunt instruments were used. However, achieving hemostasis in the IVB/MIVS group seemed much easier than in the 20-gauge PPV group, as reflected by the substantial differences in the scoring of the intraoperative bleeding between the groups. Of the 31 eyes in the IVB/MIVS group, the neovascular component of the fibrovascular membranes regressed with the reduced size of the abnormal new vessels during surgery. Most bleeding during membrane dissection or peeling was minor and some stopped spontaneously. Even if prominent bleeding occurred during membrane removal, it stopped in most cases with direct compression of the bleeding point with the blunt tip of the vitrectomy. This technique (see Video 3, available at http://aaojournal.org) is feasible using small-gauge instruments and is attributed partly to the fact that bevacizumab reduces the retinal neovascular activity. Reducing the use of cautery to achieve hemostasis may eliminate coagulative damage to the normal retinal vessels and time wasted in instrument exchanges. The significantly shorter operating time in the IVB/MIVS group was noteworthy. Although a previous study42 that compared the surgical times between 25- and 20-gauge vitrectomy reported that the 5 to 10 minutes needed for wound creation and closure in the 25-gauge group are equalized by the longer vitrectomy because intraoperative manipulation may cause more difficulties with a small-gauge system, the current results showed that the shortened time of approximately 40 minutes in the IVB/MIVS group not only was associated with easy wound creation and closure but also was more likely related to efficient intraoperative manipulation. The incidence of postoperative complications in this study was similar between groups. As reported recently, postoperative development of anterior segment neovascularization, that is, INV/NVG, no longer was common in modern diabetic vitrectomy,43 and no new INV/NVG was encountered during follow-up. However, progression or recurrence of preexisting INV/NVG occurred in both groups. Furthermore, preoperative injection of bevacizumab also failed to prevent postoperative hemorrhages in all patients in the IVB/MIVS group. Bevacizumab may be washed out during vitrectomy and the severity of retinal ischemia may be underestimated or masked by bevacizumab-induced regression of neovascularization; hence, recurrence of neovascularization and vitreous hemorrhage may appear soon after surgery before the intraoperative endolaser treatment is effective. Because preoperative and postoperative INV/NVG and postoperative vitreous hemorrhage cause severe vision loss after surgery,13 reinjection of bevacizumab should be considered at the end of surgery. The incidence of postoperative retinal redetachment did not differ significantly between groups, that is, 5% in the IVB/MIVS group and 12% in the 20-gauge PPV group, and was comparable with rates reported recently (3% to approximately 11%).25, 43 The recent preference for a panoramic viewing system during vitrectomy and current surgeon recognition of not creating a sclerotomy has reduced the occurrence of sclerotomy-related breaks and related postoperative retinal redetachments. Instead, progressive fibrovascular proliferation is still a major postoperative complication that can cause subsequent retinal redetachment. Intravitreal injection of an anti-inflammatory, an anti-VEGF agent, or both, at the end of surgery may suppress intraocular reproliferation after surgery for severe PDR. Cataract progression is a major vision-threatening complication after diabetic vitrectomy.6, 25 Because crystalline lens-sparing diabetic vitrectomy tends to have a higher subsequent reoperation rate,43 phacoemulsification and IOL implantation were combined with vitrectomy in the presence of lens opacification.19, 44 As a result, there were fewer phakic patients after surgery in both groups in the current study who could be evaluated for postoperative cataract progression. At the same time, VA measurement 6 months after surgery can be affected less by postoperative cataract progression, and the postoperative VA seemed to reflect directly the impact of diabetic vitrectomy on visual prognosis in this series. The mean postoperative VA at the 6-month visit in the IVB/MIVS group (0.30) was better than that in the conventional 20-gauge PPV group (0.22) and reached borderline significance (P = 0.047), despite comparable baseline VAs in both groups. However, a strong impact of IVB/MIVS on visual recovery in treating diabetic TRD could not be shown because the mean VA changes at the 6-month evaluation did not differ significantly between the 2 groups (P = 0.18). Nevertheless, the higher percentage of eyes with more than 3 lines of visual improvement in the IVB/MIVS group (68%) may suggest that the shorter surgical time with fewer intraoperative complications seems to favor visual recovery synergistically using IVB/MIVS. However, a prospective, randomized study is needed to clarify this. The theoretical concerns about MIVS are the increased risk of postoperative hypotony and endophthalmitis.19, 45, 46 Although 1 case of postoperative hypotony-induced maculopathy occurred during the early study period in the IVB/MIVS group, postoperative hypotony no longer occurs because the surgical procedure was modified to a 2-step entry with aggressive suture placement in cases with leaky sclerotomies. The 74% self-sealing rate in the MIVS group was much lower than that reported previously15, 16, 18 and may be attributed to extensive peripheral vitreous shaving. Instead, that procedure and endolaser photocoagulation to the anterior retina in this series may have contributed to the absence of fibrovascular ingrowth around the sclerotomy or anterior hyaloid fibrovascular proliferation. Endophthalmitis did not develop during follow-up. The overall incidence of vitreoretinal reoperation for treating postoperative complications in the MIVS group (11%) was much lower than that in the 20-gauge PPV group (24%). However, the small numbers of patients in both groups limited the ability to determine the effectiveness of IVB/MIVS for reducing the reoperation rate of diabetic vitrectomy. Although systemic and local adverse events associated with IVB have been reported,47, 48 the rapid development or progression of TRDs induced by IVB is recognized as a new concern when treating severe PDR and retinopathy of prematurity.49, 50 In the current study, 7 eyes had acute progression of a TRD between adjunctive IVB and MIVS. The incidence of 18% in eyes with a preexisting TRD was much higher than in a recent report (5.2%) in which IVB was performed not only to treat diabetic TRD but also for other complications resulting from severe PDR.49 Therefore, the authors postulated that IVB-induced progression of TRD may occur more easily in eyes with a preexisting retinal detachment. Although progression of TRD in active PDR may be the result of natural history, all cases reported here had extremely rapid contraction after IVB that was accompanied by marked involution of the neovascular components and extensive fibrotic changes in the fibrovascular membrane. Fibrotic progression and posterior hyaloid contraction in response to the acutely decreased VEGF level may increase the tractional force and may accelerate further progression of the preexisting retinal detachment. Progression of TRD involving the macula may cause serious vision loss even after successful anatomic retinal detachment repair. This possible complication should be recognized, and a timely surgical approach should be considered after IVB. Although the time between the injection and scheduled MIVS (mean, 7.6 days; range, 2–30 days) varied widely in the current study, a significant association was not found between the interval between IVB and the scheduled MIVS and progression of TRD. Instead, the ring-shaped fibrovascular membrane formation and absence of laser photocoagulation were newly explored as the risk factors for progression of TRD after IVB in eyes with a preexisting diabetic TRD in this series. Although the current results do not negate the possibility that a longer interval between IVB and surgery may affect the progression of TRD, caution should be taken in patients with diabetic TRD with these relevant findings. Bevacizumab overdosing may be another factor that contributes to the rapid progression of a TRD. A recent study reported that 1.25 mg bevacizumab can decrease high aqueous humor VEGF concentrations to under the physiologic level in patients with diabetic TRD.51 A much lower dose of bevacizumab may hasten neovascular regression sufficiently.32 Although numerous studies have reported the efficacy of bevacizumab for treating neovascular diseases, the appropriate dose for an intravitreal injection is unknown because of the off-label use of IVB. Further studies should determine the appropriate dose of IVB. The current study had several limitations: its retrospective nature, the absence of randomization, and the different study periods of the 2 groups. The duration of retinal detachments involving the macular region, which could not be documented accurately, might have affected the visual outcomes. Minor differences in surgical techniques among the 4 surgeons also may have introduced bias into the anatomic results. Nevertheless, a consecutive series of eyes repaired with the same approach during each of the 2 different periods can eliminate the bias in case selection. In conclusion, the results demonstrate favorable anatomic and 6-month postoperative VA results with minimal intraoperative complications and good surgical efficiency in MIVS assisted by IVB as a preoperative adjunct for treating diabetic TRD. However, patients should be followed up closely after IVB and should undergo a timely MIVS to avoid TRD progression, especially in the presence of a ring-shaped fibrovascular membrane, no previous laser treatment, or both. A large, prospective, controlled study is recommended to determine the appropriate dose of bevacizumab and the long-term safety of MIVS combined with IVB to treat TRD secondary to severe PDR. Supplementary data Video 1. VidClip of single-hand technique for fibrovascular membranes dissection only using a 25-gauge vitrectomy. Because the ports are small and the distances from the ports to the tips are shorter than those of a conventional 20-gauge vitrectomy, the port of the small-gauge vitrectomy can be inserted readily between the fibrovascular membrane and retina, allowing successful membrane segmentation, dissection, and removal using a 25-gauge vitrectomy only. Video 2. VidClip of bimanual technique for fibrovascular membranes dissection. 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1 Department of Ophthalmology, Osaka University Medical School, Osaka, Japan 2 Department of Ophthalmology, Kagawa University Faculty of Medicine, Kagawa, Japan 3 Department of Ophthalmology, Shiga University of Medical Science, Shiga, Japan  Correspondence: Yusuke Oshima, MD, Department of Ophthalmology, Osaka University Medical School, Room E7, 2-2 Yamadaoka, Suita 565-0871, Japan
Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article. Supported in part by research grants from the Ministry of Education, Science and Culture, Tokyo, Japan. PII: S0161-6420(08)01146-9 doi:10.1016/j.ophtha.2008.11.005 © 2009 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved. | |
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