Autologous conjunctival resurfacing of leaking filtering blebs1

Autologous conjunctival resurfacing of leaking filtering blebs1

Autologous Conjunctival Resurfacing of Leaking Filtering Blebs Lindsey D. Harris, MD1, George Yang, MD,1 Robert M. Feldman, MD1,2, Ronald L. Fellman, ...

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Autologous Conjunctival Resurfacing of Leaking Filtering Blebs Lindsey D. Harris, MD1, George Yang, MD,1 Robert M. Feldman, MD1,2, Ronald L. Fellman, MD,3 Richard J. Starita, MD,3 John Lynn, MD,3 Alice Z. Chuang, PhD1 Purpose: To present a case series of a new technique to repair late bleb leaks. Design: Retrospective, noncomparative, consecutive case series. Participants: Forty-seven autologous conjunctival resurfacings of late bleb leaks were performed by four surgeons at two institutions. Methods: Autologous conjunctival grafts were placed over existing de-epithelialized leaking blebs. Main Outcome Measures: Leak-free, Seidel-negative blebs and controlled glaucoma. Results: After a mean follow-up of 14 ⫾ 12 months, one patient continued to have bleb leak at the last follow-up, and one frank leak resolved with aqueous suppression. Intraocular pressure increased from 6.6 ⫾ 4.4 mmHg (0.13 glaucoma medications) to 11.9 ⫾ 4.1 mmHg (0.41 glaucoma medications). Conclusions: Conjunctival resurfacing with autologous tissue is an effective technique to repair late bleb leaks. Ophthalmology 2000;107:1675–1680 © 2000 by the American Academy of Ophthalmology. With the introduction of antifibrotic regimens, including mitomycin C (MMC) and 5-fluorouracil (5-FU), late bleb leaks have increased in frequency.1– 6 Management of late bleb leaks is difficult but important. Leaks predispose to hypotony,7 hypotony maculopathy,7 choroidal effusions,7,8 blebitis,7,9 and endophthalmitis.7–11 Many methods are used to repair late bleb leaks. As is generally the case when multiple procedures exist, none is universally successful. Aqueous suppression,12 autologous blood patch,8 fibrin glue,13 collagen shields,14 argon lasers,15,16 and continuouswave neodymium:yttrium–aluminum– garnet (Nd:YAG) laser treatment17,18 have been used with variable success. More invasive surgical methods are commonly required, such as hood procedures, free conjunctival patch grafts with removal of the existing bleb,12 and scleral grafts7 to limit flow through the sclerostomy. The purpose of this paper is to report the results of a new surgical technique to repair late bleb leaks while maintaining adequate filtration.

Patients and Methods Charts of all patients who underwent autologous conjunctival bleb resurfacing (ACBR) for persistent conjunctival bleb leaks from August 1994 through October 1998 were identified by review of surgical logs of four of the authors (RMF, RLF, RJS, JL). Charts were reviewed for demographics; visual acuity, intraocular pressure (IOP) measurements, and medications used before trabeculectomy; adjuvants applied during trabeculectomy; visual acuity, IOP measurements, and medications used on the date of bleb leak; number of months between trabeculectomy and bleb leak; prior failed attempts to repair bleb leak; date of ACBR; and complications of ACBR. Additionally, charts were reviewed for visual acuity, IOP measurements, medications used, recurrence of bleb leak, and any interventions to the eye on postoperative days 1, 7, 30, 90, and at the last postoperative follow-up. The data were collected by two of the authors (LDH, GY) and entered directly into a computerized database.

Statistical Analysis Originally received: October 25, 1999. Accepted: April 27, 2000. Manuscript no. 99521. 1 Hermann Eye Center, University of Texas Health Sciences Center at Houston, Houston, Texas. 2 Center for Health Care, Memorial Hermann Hospital Systems, Houston, Texas. 3 Glaucoma Associates of Texas, Dallas, Texas. Presented in part at the joint meeting of the American Academy of Ophthalmology and the Congress of the Pan-American Association of Ophthalmology, Orlando, Florida, October 1999. Supported by grants from the Hermann Eye Fund; the National Eye Institute (Core Grant); and Research to Prevent Blindness, New York, New York (grant no.: 5). The authors have no proprietary interest in the products or devices mentioned herein. Reprint requests to Robert M. Feldman, MD, Hermann Eye Center, 6411 Fannin Street, 7th Floor, Houston, Texas 77030. © 2000 by the American Academy of Ophthalmology Published by Elsevier Science Inc.

All computation was performed using SAS for Windows (SAS, North Carolina) NT version 6.12. A P value less than 0.05 was considered statistically significant. The demographics of sex and race were calculated based on the number of patients in the study. All other calculations were based on the number of eyes. Data are reported as mean plus or minus standard deviation for the age at trabeculectomy, time interval between trabeculectomy and date of leak, duration of follow-up, and IOP before trabeculectomy (where available), on the day of the leak, and after surgery on days 1, 7, 30, 90, and at the last follow-up visit. Frequency is reported for the number of leaks at days 1, 7, 30, 90, and the last follow-up visit. A one-way analysis of variance was used to compare among surgeons the change in IOP before surgery with that after surgery at 90 days and at the last follow-up. A Fisher exact test carried out the comparison among surgeons for the number of leaks and incidence of recurrent leak at each visit. ISSN 0161-6420/00/$–see front matter PII S0161-6420(00)00280-3

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Ophthalmology Volume 107, Number 9, September 2000 Surgical Technique The surgical technique, with minor variations among the surgeons, is as follows. A superior traction suture is placed, and the eye is rotated downward. The border of the ischemic bleb is then dissected from healthy surrounding conjunctiva and Tenon’s capsule with sharp Wescott scissors. The host tissue is lightly undermined approximately 2 to 4 mm. A persistent cuff of hypertrophic elevated conjunctiva at the perimeter of the avascular bleb is carefully removed with Vannas scissors (SAS, North Carolina). Absolute alcohol is then wiped across the epithelium of the bleb using a lightly soaked cellulose sponge until no viable epithelium remains. Care is taken to not allow alcohol to touch the free edge of healthy conjunctiva. The area is then profusely irrigated with balanced salt solution. A shallow lamellar keratectomy is fashioned at the limbus, creating a space for suturing the patch. Any portion of the bleb anterior to the limbus is excised. If the bleb is dysesthetic or if the eye is hypotonous, light cautery is applied to shrink the bleb. The avascular bleb is then measured with a caliper both horizontally and vertically, and an additional 1 to 2 mm in both directions is added to allow for postoperative shrinkage of the bleb. The traction suture is temporarily released, and an additional inferotemporal corneal traction suture placed, if needed, to expose the inferotemporal conjunctiva. The appropriate area of conjunctiva is measured and outlined with a marking pen. The conjunctiva and underlying Tenon’s capsule are harvested, the inferior traction suture is removed, and the denuded sclera is left untouched. The eye is again rotated downward, the limbal edge of the harvested conjunctiva is placed at the limbus over the lamellar keratectomy site, and the patch is lined up with the rest of the avascular bleb. The anterior corners of the patch are sutured to the cornea using 9-0 nylon on a VAS 100 needle (Ethicon 5890 New Jersey) so the corners of the graft approximate the free edges of the conjunctiva. The two posterior corners are similarly sutured to healthy conjunctiva. If the eye is hypotonous, the anterior chamber is filled with either viscoelastic or balanced salt solution to aid in suturing. A running horizontal mattress suture (9-0 nylon) is extended from the limbus posteriorly along each side of the graft until meeting along the posterior margin, where they overlap and are tied down. The graft epithelial edges are approximated to the edges of the healthy host tissue. Great care is taken to keep the running suture continually taut. The anterior margin of the conjunctiva is carefully sutured into the lamellar keratectomy using the technique reported by Wise.19 Balanced salt solution is injected into the anterior chamber through a preplaced paracentesis, and the suture line is checked for leaks. If leaks are present, additional interrupted 9-0 nylon sutures are placed to close the leaks. Antibiotic ointment is placed in the eye after removal of the traction suture.

Postoperative Treatment Regimens Postoperative treatment includes 7 days of topical antibiotics and topical corticosteroids for 3 weeks, then tapered.

Success Criteria Success criteria are no bleb leaks later than 1 month after surgery and, with adequate IOP, no further surgical intervention for glaucoma.

Results Forty-seven eyes of 45 patients were identified. Two patients had bilateral ACBRs. Forty-five charts were reviewed. At the time of

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Table 1. Demographics Sex Female Male Race White Black Age Mean Range Adjuvants in previous trabeculectomy MMC 5-FU None Unknown No. that had prior attempts to stop bleb leak No Yes Time between trabeculectomy and bleb leak Mean Range

23 (51.1%) 22 (48.9%) 29 (64.4%) 16 (35.6%) 61.2 ⫾ 19.4 years 12.6 to 90.3 years 27 (57.4%) 10 (21.3%) 4 (8.5%) 6 (12.8%) 31 (66%) 16 (34%) 6.3 ⫾ 13.7 years 0.2 to 28.1 years

Table 1 describes the demographics of the study’s patient population. Sex and race were calculated based on the number of patients. All other calculations were based on the number of eyes treated with ACBR. Calculations include mean ⫾ standard deviation.

review, all patients were at least 90 days past the ACBR procedure. All 47 ACBRs were performed without intraoperative complications. The demographics for the group are shown in Table 1. Sixteen eyes (34%) had undergone attempts before ACBR to stop the bleb leak. Eight were treated with aqueous suppression, three with laser remodeling, three with autologous blood patches, one with sutures, and one with bandage contact lenses. Data were available for 3 months after surgery on 43 of 47 eyes. Thirty-seven eyes had postoperative data past 90 days. The mean interval of follow-up was 14 ⫾ 12 months. The four patients lost to follow-up at 90 days returned to the referring physician for follow-up care; one patient returned to the surgeon after 1 week, and three patients returned more than 1 month after surgery. None were referred again for recurrent leak. Table 2 shows recurrence of bleb leaks after ACBR. Early leaks are defined as frank Seidel-positive leaks occurring at or before 30 days after surgery, which are not considered failures unless the leak did not resolve by postoperative day 30. At postoperative day 1, two leaks occurred; by postoperative day 7, eight leaks had occurred; but by postoperative day 30, only four leaks occurred. On postoperative day 1, one patient had a hole in the graft that was resutured. The hole was also sutured on postoperative days 2, 5, 8, and 12. Subsequently, the eye was leak free and had an uncomplicated, successful postoperative course. Between 7 days and 30 days after surgery, 10 eyes were resutured. One of the eyes was just described. One eye was leak free, but was resutured to replace a broken suture. Six were resutured once, and two of the six received additional aqueous suppression. These patients remained leak free throughout the follow-up. Two eyes were sutured twice during this interval, and both received aqueous suppression. One leak resolved completely, but one continued to leak after 30 days. Two eyes had frank leaks at 90 days after surgery. The eye described above, that was treated with sutures twice and aqueous suppression, continued to leak at 90 days after surgery. However, the leak resolved, and the eye was still leak free at the last follow-up at 31 months. The second eye, which had a frank leak at 90 days after surgery, began leaking at this time. It was treated

Harris et al 䡠 Conjunctival Resurfacing Table 2. Total Number of Leaks and IOP No. Leaks Pretrabeculectomy 0 Day of indication 47 Day 1 2 Day 7 8 Day 30 4 Day 90 2 Last post-op follow-up 1

Intraocular Pressures

Glaucoma Medications

Mean 26.1 ⫾ 11 mmHg Range 11 to 58 mmHg Mean 6.6 ⫾ 4.4 mmHg Range 0 to 18 mmHg

0.13

Mean 10.6 ⫾ 5.4 mmHg Range 0 to 24 mmHg

0.00

Mean 10.2 ⫾ 5.4 mmHg Range 0 to 29 mmHg

0.09

Mean 14.4 ⫾ 7.4 mmHg Range 4 to 40 mmHg

0.33

Mean 13.6 ⫾ 5.5 mmHg Range 4 to 36 mmHg

0.37

Mean 11.9 ⫾ 4.1 mmHg Range 4 to 22 mmHg

0.41

Table 2 describes the number of leaks and the IOP pretrabeculectomy, on the day bleb leak was initially seen by the surgeon, and on postoperative days 1, 7, 30, 90 and last follow-up visit. IOP calculations include mean ⫾ standard deviation. The number of glaucoma medications is also included and was calculated as a mean.

with aqueous suppression. It continued to leak until the last visit at 16 months after surgery. Table 2 shows the mean IOPs for the group. Mean IOP on the day of diagnosis of bleb leak was 6.6 ⫾ 4.4 mmHg (0.13 glaucoma medications), which increased by the last visit to an IOP of 11.9 ⫾ 4 mmHg (0.41 glaucoma medications). No surgical interventions were used to decrease IOP after ACBR. The number of postoperative leaks between surgeons was significant at day 1, but insignificant at days 7, 30, 90, and at the last follow-up. The difference among surgeons in the change in IOP before surgery to that after surgery on day 90 and at the last follow-up was not significant. Figure 1 shows an ischemic leaking bleb before ACBR was performed. Figure 2 shows the avascular bleb on postoperative day 1. After surgery, the bleb began to vascularize by postoperative day 3. Vascularization continued until it was complete by 1 month after surgery. Figure 3 shows a fully vascularized bleb on postoperative day 90.

Discussion Cystic, thin-walled avascular bleb leaks are increasingly common with long-term follow-up of trabeculectomies performed with adjunctive 5-FU or MMC.1– 6 5-Fluorouracil and MMC inhibit fibroblast proliferation and result in thinner, more friable blebs. The Fluorouracil Filtering Surgery Study1–3 reported a higher incidence of late-onset bleb leaks compared with the control group at 1-, 3-, and 5-year follow-ups. At the 1-year and 3-year follow-ups, seven of 105 eyes (7%) treated with 5-FU had bleb leaks, compared with zero of 108 eyes in the control group. The number of late bleb leaks increased at the 5-year follow-up, with nine

Figure 1. Thin, ischemic leaking bleb. Figure 2. Autologous conjunctival bleb resurfacing on postoperative day 1. An avascular bleb is shown. Figure 3. Autologous conjunctival bleb resurfacing on postoperative day 90. A fully vascularized bleb is shown.

of 105 eyes (9%) treated with 5-FU experiencing bleb leaks compared with two of 108 eyes (2%) in the control group. Tsai et al4 reported the incidence of bleb leaks occurring after trabeculectomy for neovascular glaucoma with adjunctive 5-FU to be one of 34 eyes (3%), with a median

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Ophthalmology Volume 107, Number 9, September 2000 follow-up of 12.5 months. In a study by Belyea et al5 of 385 eyes treated with 5-FU and MMC, the incidence of bleb leaks was 1.8%, with a mean follow-up of 20.4 months (range, 9 – 44 months). One hundred ninety-three eyes (50.1%) were treated with 5-FU (total dose range, 12.5– 40 mg), with only five leaks occurring. Meanwhile, of the 192 eyes (49.9%) treated with MMC (total dose range, 0.25– 0.5 mg/ml for 3– 4.5 minutes), only two leaks were recognized. A study of 525 eyes by Greenfield et al6 reported bleb leaks occurring more commonly in MMC-treated eyes, with 10 bleb leaks occurring in 273 eyes (3.7%), with a mean follow-up of 1.7 ⫾ 1.3 years compared with 5-FU–treated eyes, in which three bleb leaks occurred in 213 eyes (1.4%), with a mean follow-up of 3.6 ⫾ 2.6 years and compared with the group without antifibrotics, in which one of 39 eyes (2.6%) experienced bleb leaks. The results of Perkins et al’s20 2- to 3-year follow-up of 68 patients who had undergone trabeculectomy with adjuvant MMC showed a 4% occurrence of late bleb leaks. Complications of bleb leaks include hypotony with or without subsequent macular edema, shallow anterior chamber, choroidal detachment, blebitis, and endophthalmitis. In a recent series of 12 eyes with recurrent multiple bleb infection,9 11 had undergone trabeculectomy with antimetabolites or alkylating agents. Since introduction of 5-FU and MMC into trabeculectomy, doses commonly used have decreased from 140 mg total for 5-FU and 0.5 mg/ml of MMC in place for 5 minutes to more commonly less than 10 mg of 5-FU and 0.2 mg/ml of MMC in place for 2 minutes or less.21,22 This may reduce the frequency of late leaks, which occurred in this study on average of 6 years after the initial surgery. Management of bleb leaks is challenging. Typically, initial treatment is aqueous suppression, prophylactic antibiotics, and observation. This is inadequate as a long-term solution because these leaks spontaneously resolve and reappear elsewhere within the ischemic bleb. Furthermore, a very thin bleb is still present, allowing easy penetration of bacteria into the bleb. Other techniques used are: autologous blood injections,12 glue,13 argon laser,15,16 and continuouswave Nd:YAG laser.17,18 Autologous blood injections were performed on six patients in a case series by Smith et al,8 which were successful after 4 to 12 months of follow-up in four of the six patients. Others believe that results have been disappointing, even after multiple blood patches. Another recent case series by Gammon et al13 on autologous fibrin glue showed success in one of three patients. In Hennis and Stewart’s15 case series, 15 bleb leaks were treated with argon laser. Thirteen of the 15 leaks closed, but complications of conjunctival fenestration and pitting occurred in three eyes and corneal stromal opacities occurred in one eye after applying the argon laser at the conjunctival– corneal interface. Lynch et al’s17 case series of bleb leaks and hypotony treated with continuous-wave Nd:YAG laser had four of five bleb leaks to be closed at last follow-up (mean, 10.5 months). In the one failed eye, another leak, an iatrogenic leak, occurred after closure of the first bleb leak. It was retreated using the laser, and a larger leak formed in an area of pigmentation made by the first treatment procedure. After aqueous suppression and patching, the leak healed. Disadvantages included iatrogenic leaks, the pigmentation

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precipitated by the laser treatment that can affect future laser treatment, and pupil flattening or peaking. In a subsequent recent case series on Nd:YAG laser conducted by Geyer,18 five of five eyes with leaking blebs healed after laser treatment. However, in all five, iatrogenic leaks developed that healed with aqueous suppression and patching, and in two eyes pupil retraction developed. The continuouswave Nd:YAG laser is not readily available to most surgeons and is expensive. Thus no long-term data are available. More invasive surgical procedures have also been tried to manage bleb leaks. In 1964, Iliff23 described closing a conjunctival fistula with a conjunctival flap moved from above over the pre-existing bleb. More recently, in 1992, O’Connor et al24 modified this with excision of the bleb and relaxing incision in the superior fornix to bring Tenon’s fascia and conjunctiva down over the filtration area. They reported success in five patients. However, long-term follow-up and IOPs were not reported. Six years ago, Wilson and Kotas-Neumann12 reported using a free conjunctival patch to repair bleb leaks after bleb excision. They reported successful bleb leak closure in four patients. One patient was leak free at 1 year, whereas three patients were leak free at 2 months. One half of the patients used glaucoma medication to maintain adequate IOP. In 1997, Kosmin and Wishart7 reported using full-thickness scleral graft after bleb excision to stop bleb leaks in eight eyes. They successfully repaired eight bleb leaks and had adequate follow-up. However, two of eight patients (25%) experienced IOP spikes after surgery that were treated by loosening sutures that held the scleral graft in place. Three of the eight eyes in the study required glaucoma medication to maintain IOP less than 22 mmHg. This may be a good option for overfiltration through the fistula rather than for bleb leaks. Amniotic membrane transplantation is currently under investigation for conjunctival resurfacing. A case series by Tseng et al25 recently reported on efficacy of amniotic membrane transplantation in seven eyes after removal of large conjunctival lesions and in nine eyes after removal of conjunctival scars or symblepharon. With a mean follow-up of 10.9 ⫾ 9 months, 11 eyes were reported as successful without recurrence, and two eyes were reported as partially successful because of conjunctival inflammation. However, three eyes failed and showed recurrent scarring. Although the indication for intervention in this case series was not bleb leak, it did show questionable efficacy of the procedure. The ACBR procedure described in this article effectively stopped leaks with minimal interference with bleb filtration. Of the two late frank leaks that recurred, one healed with aqueous suppression after 90 days after surgery and continued to remain leak free at 31 months after surgery. The one late frank leak that did not resolve was performed on a patient with malformed lids that traumatized the ACBR. The procedure initially resulted in a leak-free state, but the bleb dried out and releaked, which could be attributed to the lid’s configuration. The bleb continued to leak at 16 months after surgery. The sutures that were placed within the early interval after surgery stopped early leaks, yet aqueous suppression

Harris et al 䡠 Conjunctival Resurfacing also helped in reaching leak-free status in four of the nine eyes. These leaks were at suture lines and not within ischemic blebs, with the exception of one patient. This patient required multiple resuturing of the graft after experiencing a stretch hole within the graft. Resuturing is not performed routinely. Aqueous suppression is the recommended management of early leaks occurring after ACBR. Autologous conjunctival bleb resurfacing may be successful because it places autologous conjunctiva over the bleb (no excision is performed), stopping the bleb from leaking immediately and then providing new cells, nutrients, chemotactic factors, growth factors, and vascularity, which work to provide epithelialization of the bleb even if the graft retracts. Intraocular pressure is maintained with this procedure because the size of the bleb is not reduced, and even though the bleb is slightly thickened, it is still relatively thin. Because only one of these two parameters is affected, adequate filtration of the bleb is still maintained with only a small increase in IOP. In this study, the IOP levels increased from 6.6 ⫾ 4.4 mmHg before surgery to 11.9 ⫾ 4.1 mmHg at the last follow-up visit, which are healthy IOP measurements. Additionally, the change in IOP between preoperation, postoperative day 90, and at the last follow-up was insignificant among the surgeons. The number of glaucoma medications used to help maintain lower IOP did increase slightly from 0.13 to 0.41 medications. However, the number of glaucoma medications used after surgery in this case series was still less than that reported in other studies. Thus this procedure has the potential to allow for long-term, leak-free, glaucoma control. This is the largest series (47 procedures) of a single technique to repair late bleb leaks. Autologous conjunctival bleb resurfacing procedures in this series were performed by four surgeons using similar techniques, indicating that the procedure is reproducible and that its results should be generalizable. In comparing the number of leaks that occurred among surgeons, the P value was only significant at day 1. Although this P value was significant, the patients of only two surgeons experienced one leak. This small number of leaks indicates that this may not be a real phenomenon. Additionally, a broad distribution of patient demographics, including patients with 5-FU and MMC adjuvants and some without antiproliferative regimens, are included in the study, indicating that it is effective regardless of antifibrotic regimen use. The cases were consecutive, and all patients were accounted for at the end of the study. Weaknesses of the study include possible misclassification by the surgeons of a bleb leak versus an ooze. Bleb leak can be defined as fluid flowing through a hole in the bleb as compared with an ooze, which is normally present in ischemic filtering blebs and represents transconjunctival flow. Also, follow-up and evaluation for leaks with Seidel testing was not performed at every postoperative visit because postoperative follow-up criteria specifying Seidel testing was not delineated at the time of surgery, which is attributable to the retrospective nature of this chart review. The natural history of this disorder remains unclear. Some cases undergo spontaneous resolution, continued leakage, and intermittent leakage from new sites. In conclusion, in patients with late-leaking filtering blebs

who are at risk for infection, ACBR is an effective initial surgical treatment.

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Ophthalmology Volume 107, Number 9, September 2000 mitomycin C: intermediate-term results. J Glaucoma 1998;7: 230 – 6. 21. Singh J, O’Brien C, Chawla HB. Success rate and complications of intraoperative 0.2 mg/ml mitomycin C in trabeculectomy surgery. Eye 1995;9:460 – 6. 22. Dietze PJ, Feldman RM, Gross RL. Intraoperative application of 5-fluorouracil during trabeculectomy. Ophthalmic Surg 1992;23:662–5.

23. Iliff CE. Flap perforation in glaucoma surgery sealed by a tissue patch. Arch Ophthalmol 1964;71:215– 8. 24. O’Connor DJ, Tressler CS, Caprioli J. A surgical method to repair leaking filtering blebs. Ophthalmic Surg 1992;23: 336 – 8. 25. Tseng SCG, Prabhasawat P, Lee SH. Amniotic membrane transplantation for conjunctival surface reconstruction. Am J Ophthalmol 1997;124:765–74.

Historical Image

Text and images courtesy of John Kearney, MD and Stephen Tanaka, MD, Hayward, California.

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