Longterm follow-up of diode laser transscleral ... - Wiley Online Library

Acta Ophthalmologica 2010

Longterm follow-up of diode laser transscleral cyclophotocoagulation in the treatment of refractory glaucoma Paolo Frezzotti, Vincenzo Mittica, Gianluca Martone, Ilaria Motolese, Luca Lomurno, Sabrina Peruzzi and Edoardo Motolese Department of Ophthalmology and Neurosurgery, University of Siena, Siena, Italy

ABSTRACT. Purpose: This prospective study was conducted to evaluate the efficacy and safety of transscleral diode laser cyclophotocoagulation (TDLCP) in advanced refractory glaucoma. Methods: A total of 124 eyes in 121 patients with advanced glaucoma refractory to medical treatment were treated consecutively with TDLCP. Success was defined as final intraocular pressure (IOP) of 5)21 mmHg in eyes with visual acuity (VA) of more than hand movements (HM) and relief of pain in eyes with VA of HM or less, including blind eyes. Results: Mean patient age was 65.6 ± 17.1 years (range 14–91 years). Mean follow-up was 17 ± 14.6 months (range 3–42 months). Mean pretreatment IOP was 29.9 ± 8.4 mmHg (range 17–58 mmHg) and IOP at last follow-up was 20.8 ± 8 mmHg (range 6–45 mmHg) (p < 0.001). The number of laser applications (mean 9.2 ± 2.8, range 4–15) and maximal laser power (mean 2.01 ± 0.22 mW, range 1.3–3.0 mW) were not associated with lower postoperative IOP. Intraocular pressure of £ 21 mmHg was recorded in 63.0% of eyes at the last follow-up visit. Overall, 28 (21.7%) eyes required at least one retreatment. No phthisis bulbi or persistent hypotonia developed. Conclusions: TDLCP is an effective and safe method for the treatment of advanced refractory glaucoma, although repeated treatments are often necessary. Key words: diode laser cyclophotocoagulation – glaucoma – intraocular pressure – treatment

Acta Ophthalmol. 2010: 88: 150–155 ª 2009 The Authors Journal compilation ª 2009 Acta Ophthalmol

doi: 10.1111/j.1755-3768.2008.01354.x

Introduction For many years, refractory forms of glaucoma have been treated by techniques aimed at destroying the ciliary

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body (Weekers et al. 1961; Beckman et al. 1972; Beckman & Sugar 1973; Lee 1979). These include cyclocryotherapy proposed by Bietti (1950) and still used, and more modern tech-

niques such as cyclophotocoagulation with Nd:YAG laser (Hampton et al. 1990; Suzuki et al. 1991) (1064 nm), proposed in the second half of the 1980s, and cyclophotocoagulation with diode laser. In transscleral diode laser cyclophotocoagulation (TDLCP), cyclodestruction is achieved by transscleral application of infrared light (810 nm), which has the theoretical advantage of better penetration and selective absorption by the pigmented tissue of the ciliary body, resulting in destruction of the ciliary epithelium and coagulation necrosis of ciliary body stroma (Schuman et al. 1990; Simmons et al. 1994; Feldman et al. 1997). TDLCP is a widely used method of ciliary body ablation, with reported success rates of 40)80% (Brancato et al. 1995; Wong et al. 1997; Spencer & Vernon 1999; Mistlberger et al. 2001; Schlote et al. 2001). Laboratory studies have shown that diode wavelength in TDLCP is nearly twice as efficient as the Nd:YAG wavelength (Rol et al. 1990; Vogel et al. 1991). The risk of side-effects seems to be significantly lower with TDLCP than with cyclocryotreatment. Hypotonia and phthisis rarely occur (Bloom et al. 1997). TDLCP provides effective and safe management of eyes with glaucoma that cannot be controlled medically or surgically


(Brancato et al. 1995; Kosoko et al. 1996). Little is known about the risks and efficacy of the procedure for different types of glaucoma, and risks and prognostic factors other than glaucoma type have yet to be determined. The aim of this study was to evaluate prospectively the efficacy and safety of TDLCP in advanced refractory glaucoma.

Materials and Methods In June 2000, we started a prospective study of TDLCP in consecutive cases of advanced glaucoma refractory to medical, surgical and alternative treatment. All operations were performed in the Department of Ophthalmology and Neurosurgery, University of Siena, Italy. Informed consent was obtained from all patients prior to enrolment in the study. The study was performed in accordance with the Declaration of Helsinki and with local ethical approval. Patients underwent TDLCP for one of the following indications: (1) advanced glaucoma uncontrolled by maximum medical treatments and refractory to surgical or laser treatment; (2) glaucoma uncontrolled by maximum medical treatments, in which treatment with surgery or other laser modalities was unlikely to control intraocular pressure (IOP) (e.g. neovascular glaucoma); (3) advanced glaucoma intolerant of medical treatment, in an attempt to reduce or suspend medication, or if the patient declined surgical treatment; (4) advanced glaucoma with eye discomfort and reduced visual capacity, and (5) systemic conditions contraindicating surgery. Before recruitment, patients underwent baseline examination, which included full ophthalmic examination (slit-lamp biomicroscope examination and funduscopy), visual field examination (Humphrey Field Analyser 30.2; Humphrey Instruments Inc., San Leandro, CA, USA), Snellen visual acuity (VA), IOP and determination of the cause of glaucoma. Treatment was defined as successful if IOP was reduced to 5–21 mmHg with or without medication in all eyes

with VA of more than hand movements (HM). In eyes with VA of HM or less, including blind eyes, TDLCP was performed to reduce pain or to avoid further complications and enucleation. A total of 157 TDLCPs were performed in 124 eyes of 121 patients (mean age 65.6 years, range 14– 91 years) with the following forms of glaucoma: primary open-angle; aphakic; neovascular; chronic angleclosure; silicone oil; traumatic; paediatric; uveitic, and other miscellaneous types (Table 1). Of these eyes, 31.0% had previously undergone surgery, 0.8% by cyclocryotherapy and 1.6% by Nd:YAG laser cyclophotocoagulation (Table 2).

Table 1. Demographic data for study eyes (121 patients, 124 eyes). n (%) Mean age, years 65.6 (range 14–91) Sex Female Male Type of glaucoma Primary open-angle Aphakic Neovascular Chronic angle-closure Silicone oil Traumatic Congenital or juvenile Uveitis Intraocular lens in anterior chamber Others

124 (100) 55 (44.3) 69 (55.7) 45 15 27 2 9 9 7 4 4

(36.2) (12.0) (21.8) (1.6) (7.3) (7.3) (5.6) (3.3) (3.3)

2 (1.6)

Table 2. Previous ocular surgery in 124 eyes of 121 patients with advanced glaucoma. Eyes, n (%) Trabeculectomy Trabeculotomy Cyclodiastasis Cyclodiathermy Laser trabeculoplasty YAG laser iridotomy Cyclocryotherapy Other cyclophotocoagulation Cataract surgery Pseudophakia with posterior chamber lens Pseudophakia with anterior chamber lens Aphakia Penetrating keratoplasty Vitrectomy

34 2 3 1 9 2 1 1

(27.4) (1.6) (2.4) (0.8) (7.2) (1.6) (0.8) (0.8)

34 (27.4) 2 (1.6) 15 (12.0) 1 (0.8) 9 (7.2)

All treatments were performed by authors PF and VM in the operating room. TDLCP was performed using a diode laser emitting at 810 nm through a contact probe (Zeiss Visulas II diode laser; Carl Zeiss, Jena, Germany). The procedure was performed under local anaesthesia with peribulbar and retrobulbar injections of lidocaine 2.0% + marcaine 0.5% and lidocaine 2.0%, respectively. Laser function was checked before each procedure. Standard treatment consisted of 10–15 applications (five per quadrant) of 2000 mW applied for 2.0 seconds (to obtain a maximum power per spot of 4 J). An area of 180 degrees of pars plicata was treated at the first treatment when IOP was < 25 mmHg. A 270-degree area of pars plicata was treated when IOP was > 25 mmHg and at all subsequent treatments. These treatments included all areas already treated. In cases of thinned sclera evaluated at the slit-lamp, the initial energy and duration parameters were reduced to 1500 mW and 1.5– 2.0 seconds. In cases of ‘pop effect’, indicating the photodisruption of tissue with the release of a bubble of gas, during treatment, the power was reduced in subsequent spots. At each treatment, 12–18 applications per 180 degrees were performed. The location of the ciliary body was identified with transillumination. The pars plicata was located at approximately 1.5 mm posterior to the limbus. The anterior part of the probe was placed 1.5 mm posterior to the limbus, perpendicular to the scleral wall, and was maintained in contact with light pressure. The 3 and 9 o’clock meridians were spared to avoid damaging the long posterior ciliary arteries. After each treatment, the energy used and the part of the ciliary body treated were recorded. Post-treatment medication included fluormetholone eyedrops applied three times ⁄ day for 15 days. The eye was bandaged for 6–8 hours. Antiglaucoma therapy, except myotics, was continued at least until follow-up 30 days after treatment. If IOP decreased after treatment, patients initially continued routine glaucoma medications, but these were gradually withdrawn as appropriate. Oral carbonic anhydrase inhibitors (CAIs) were withdrawn first, followed by IOP-reducing eyedrops. If IOP was not sufficiently

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35

30

29.9

Mean IOP (mmHg)

25

20

20.4

19.8

18.9

18.8

18.9

18.3

15

10

5

0 0

1

6

12

24

36

42

Time after treatment (months)

reduced after 1 month, TDLCP was repeated up to three times, after which the patient was referred for other surgical procedures and considered refractory to TDLCP. All patients underwent follow-up examinations at 1 week and 1, 3, 6 and 12 months after treatment and every 6 months thereafter. At every follow-up examination, VA, IOP, medication, slit-lamp biomicroscopic appearance, funduscopy and complications were recorded. Visual field tests were repeated at 6 months. Patients were asked to score discomfort (absent, slight or severe) after treatment. Statistical analysis of the differences between IOP and number of medications before and after treatment was carried out by Student’s t-test for paired data. P-values of £ 0.05 were considered statistically significant.

Fig. 1. Mean intraocular pressure (IOP) against time at each follow-up visit.

Results 50

Baseline IOP (mmHg)

40

30

20

10

0 0

10

20

30

40

50

Final IOP (mmHg) Fig. 2. Scattergram showing intraocular pressure (IOP) at baseline and at the end of follow-up in 124 treated eyes. Table 3. Intraocular pressure (IOP) results over time. 1 Pretreatment month Eyes, n 124 Mean IOP, mmHg 29.9 Mean IOP 0 reduction, mmHg % IOP reduction 0 p-value for IOP change )

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124 20.4 9.5

6 months

12 months

24 months

36 months

42 months

104 18.9 11

82 18.9 11

55 19.8 10.1

36 18.8 11.1

23 18.3 11.6

31.7 36.8 36.8 33.7 37.1 38.7 < 0.001 < 0.001 < 0.001 < 0.001 < 0.001 < 0.001

Table 3 shows the mean IOP at each follow-up, the number of eyes undergoing each examination, the mean and percentage reduction in IOP after treatment and the statistical significance of any reduction. Mean IOP shows a reduction of 36.8% at 6 months and 38.7% at 42 months. Mean reductions in IOP at each follow-up are shown in Fig. 1 and demonstrate a statistically significant reduction in IOP at the first check-up, maintained to month 6. Mean followup was 17 months but a small group of 36 eyes underwent ‡ 3 years of follow-up, so the figures at the end of the graph are based on smaller numbers. The difference in IOP before and after treatment is evident in Fig. 2, where eyes shown as points over the oblique line showed a reduction in IOP after treatment. Mean (± standard deviation [SD]) pretreatment IOP was 29.9 ± 8.4 mmHg; this decreased after treatment in 95.0% of eyes. At the last follow-up, 63.0% of patients had IOP < 21 mmHg, 75.0% had IOP < 25 mmHg and 89.1% had IOP < 30 mmHg. A total of 96 (77.4%) eyes underwent a single treatment; 24 (19.3%) eyes underwent two treatments; three (2.4%) eyes underwent three treatments, and one eye (0.8%) underwent four treatments. Of the 28 repeated treatments, seven TDLCP procedures


Table 4. Intraocular pressure results in relation to diagnosis. All eyes Eyes, n (%) Mean IOP pretreatment, mmHg Mean IOP post-treatment, mmHg % IOP reduction p-value for IOP change

POAG

124 (100) 29.9

Aphakic

NVG

SO

Uveitic

Traumatic

Paediatric

45 (36.2) 26.7

15 (12.0) 26.9

27 (21.7) 35.0

9 (7.2) 29.3

4 (3.2) 32.7

9 (7.2) 29.4

7 (5.6) 28.1

20.8

19.5

17.9

23.3

20.9

22.2

22.9

24

31.7 < 0.001

26.9 < 0.001

33.4 < 0.001

33.4 < 0.001

28.6 < 0.001

32.1 < 0.001

22.1 < 0.001

14.6 < 0.001

POAG = primary open-angle glaucoma; NVG = neovascular glaucoma; SO = silicone oil glaucoma; IOP = intraocular pressure.

were performed up to 4 weeks, nine up to 3 months, six up to 6 months, and six up to 12 months after the first treatment. Mean energy delivered was 36.7 ± 11.5 J in 9.1 ± 2.8 laser applications (range 4–15). Duration was 2.0 seconds in all except three treatments, in which it was 1.8 seconds. There were no significant differences in energy level between the first TDLCP and repeated TDLCPs. During coagulation, the pop effect occurred in 12 of 157 treatments (7.6%); immediate reduction of power prevented it from recurring during the same treatment. Of the 12 eyes in which the pop effect occurred, nine (75%) had a dark brown iris and three (25%) a green or blue iris. Despite repeated TDLCP, no pressure-lowering effect or relief of pain was seen in five (4.1%) of the 121 patients. These five patients were treated with trabeculectomy (one eye), cyclocryotreatment (three eyes) and enucleation (one eye). All these treatments were performed at 6 months after the initial TDLCP. In our study, 98 eyes had VA of more than HM. Intraocular pressure decreased to 5–21 mmHg in

66 (67.3%) of these eyes, falling from 28.3 ± 7.9 mmHg (range 17–58 mmHg) before surgery to 20.4 ± 7.45 mmHg (range 6–45 mmHg) at the last follow-up. Visual acuity of HM or less was recorded in 26 eyes. Seven of these eyes were blind. Relief of pain was achieved in 26 (100%) of these eyes, including all seven blind eyes, and IOP in these eyes decreased from 35.8 ± 7.9 mmHg before surgery to 24.6 ± 9.7 mmHg at the last followup visit. Table 4 shows that pre-treatment IOP was highest in the neovascular

Table 6. Complications of transscleral diode laser cyclophotocoagulation. Eyes, n (%) Pop effect Pupil distortion Anterior chamber reaction (3 + cells) Hyphaema Intravitreous haemorrhage Phthisis Bulbus hypotonia Loss of visual acuity (‡ 2 lines)

12 (7.6) 1 (0.8) 3 (2.4) 2 (1.6) 0 0 0 16 (12.9)

Table 5. Visual acuity after treatment(s).

Group

TDLCP treatments, n

Eyes, n

Final VA worse, n (%)

Final VA unchanged, n (%)

Final VA better, n (%)

1 2 ‡3 1 2 ‡3

124 96 24 4 52 13 2

28 26 1 16 1 0

91 66 22 35 12 2

5 4 1 1 0

All eyes

Pretreatment VA ‡ 20 ⁄ 200

(22.5) (27.0) (4.2) (30.7) (7.7)

(73.5) (68.7) (91.6) (67.3) (92.3) (100)

TDLCP = transscleral diode laser cyclophotocoagulation; VA = visual acuity.

(4.0) (4.3) (4.2) (2.0)

Table 7. Number of glaucoma medications. Drugs, n

Pretreatment

Last follow-up

0 1 2 ‡3 Drugs, n Mean ± SD

0 3 11 110 3.5 ± 1.0

2 5 13 104 3.3 ± 1.1

SD = standard deviation.

glaucoma group (35 mmHg), followed by the uveitic glaucoma group (32.7 mmHg), and was lowest in the primary open-angle glaucoma (POAG) group (26.7 mmHg), followed by the aphakic glaucoma group (26.9 mmHg). At final followup, IOP was lowest in the aphakic glaucoma group (17.9 mmHg), followed by the POAG group (19.5 mmHg). The overall percentage decrease in IOP as a result of laser treatment was greatest in the neovascular and aphakic glaucoma groups (both 33.4%), followed by the uveitic glaucoma group (32.1%). The highest (73.3%) and lowest (57.1%) success rates were found in the POAG and paediatric glaucoma groups, respectively. There was no correlation between age (except for congenital glaucomas), sex and reduction of IOP and drug consumption as a result of TDLCP. Patients undergoing only one treatment in the follow-up period were younger (mean age 64.6 ± 17.2 years) than patients who had repeated treatments (mean age 66.5 ± 18 years). There was no significant association between gender and probability of success (p = 0.8), which was significantly the same in the 85 eyes without previous surgery (74.1%) as in the 39

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eyes with previous ocular surgery (74.3%, p = 0.5). Table 5 summarizes changes in VA after treatment according to the total number of treatments received. Of the 67 eyes in which VA could be recorded on the Snellen chart at 6 m before laser treatment (i.e. VA ‡ 20 ⁄ 200, the eyes with the best pretreatment VA in this series), 49 (76.1%) maintained the same Snellen VA after TDLCP. Of the 67 eyes with VA ‡ 20 ⁄ 200 before treatment, 17 had worse VA (eight eyes by 3 Snellen lines, four by 2 lines and four by 1 line) at the last follow-up. Before treatment, VA < 100 ⁄ 200 in 68.5% of eyes and 20.9% of eyes were blind or perceived HM only. In eyes with VA of more than counting fingers, VA decreased in 12 eyes by ‡ 2 lines, but increased by ‡ 2 lines in three eyes. Three eyes with VA of HM and light perception (LP) before TDLCP had no LP at the last follow-up. No significant relationship between loss of VA and failure of treatment could be found. Complications associated with TDLCP are shown in Table 6. In our patients, they were: anterior segment inflammation (3 + cells) in three eyes (2.4%); hyphaema in two eyes (1.6%), and pupil distortion in one eye (0.8%). No phthisis, prolonged hypotonia (< 5 mmHg for ‡ 1 month), perforation, corneal erosion or sympathetic ophthalmia occurred during the follow-up period. Intraoperatively, pop effects occurred during 12 of 157 treatments. Table 7 shows the number of drugs administered before and after TDLCP. Before treatment, 8.8% of patients used two drugs and 88.7% used three or more (mean 3.5 ± 1.0). A total of 24.0% of patients were taking systemic CAIs with topical treatment. At the last follow-up, the mean number of drugs used dropped to 3.3 ± 1.1 (p = 0.02), with 10.4% of the same patients using two drugs and 83.8% using three or more. Furthermore, at the last follow-up visit 10.4% of patients were using systemic CAIs with topical treatment (p = 0.04).

Discussion The present results confirm those of previous studies which demonstrated

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the efficacy and relative safety of TDLCP in reducing IOP in patients with refractory glaucoma (Brancato et al. 1995; Bloom et al. 1997; Wong et al. 1997; Mistlberger et al. 2001). The treatment reduced the number of drugs needed to control IOP, thus eliminating some side-effects. This important improvement is even more significant because the patients had forms of glaucoma, such as neovascular, post-traumatic and aphakic glaucoma, and glaucoma caused by silicone oil, which are notoriously difficult to resolve by conventional techniques. Moreover, most patients had already had unsuccessful experiences with surgery or parasurgical treatment. There were no cases of phthisis, hypotonia or marked activation of the underlying inflammatory disease. The efficacy of TDLCP was demonstrated by the reduction in IOP observed 1 month after treatment. This reduction was substantially unchanged 6 months later, averaged about 30.0% and persisted throughout the follow-up period. Our prospective study reports the results of TDLCP in a heterogeneous glaucoma population with a mean follow-up period of 17 months. The overall probability of success was 74.1% and is similar to results obtained by other authors (Yap-Veloso et al. 1998; Youn et al. 1998). Relief of pain probably resulted from the destruction of sensory innervation of the anterior segment, as shown experimentally for cyclocryotherapy (Werner et al. 1998), and may be relatively independent of reduction of IOP. The heterogeneity of the population treated demonstrated the efficacy of the technique in a wide range of forms of glaucoma, some with very different natures and clinical histories. Although most patients were over 65 years of age, the results obtained in younger patients suggest that young age may not, after all, be such a major risk factor for failure of TDLCP. However, larger numbers of patients are needed to better understand the possible effects of TDLCP treatment on paediatric, traumatic and uveitic glaucoma. The need to wait a month in order to evaluate the outcome of cyclophotocoagulation is a disadvantage because time is precious in the struggle to maintain some visual capacity.

The greatest reductions in IOP were achieved in neovascular and aphakic (33.4%) and uveitic (32.1%) glaucoma. The results were relatively poor for paediatric (14.6%) and traumatic (22.1%) glaucoma. Compared with other types of glaucoma, neovascular glaucoma often shows an unsatisfactory decrease in IOP and severe complications after cyclocryotherapy (Benson & Nelson 1973; Brindley & Shields 1986) and after non-contact and contact Nd:YAG laser (Hampton et al. 1990; Shields & Shields 1994). By contrast, in some studies (Bloom et al. 1997; Yap-Veloso et al. 1998) and in the present study, neovascular glaucoma showed the greatest mean decrease in IOP without severe complications. These findings support the observation that TDLCP should be regarded as the cyclodestructive procedure of choice for the treatment of neovascular glaucoma. Regarding aphakic glaucoma, different results have been reported after TDLCP (Brancato et al. 1995; Bloom et al. 1997; Yap-Veloso et al. 1998). Our results suggest that TDLCP is an effective alternative for types of glaucoma related to poor surgical outcomes. Uveitic glaucoma is a frequent complication of inflammatory eye disease in which trabeculectomy or cyclocryotherapy are always associated with a high risk of failure (Veldman & Greve 1987). The results of this study indicate that TDLCP is a safe and effective method for the treatment of uveitic glaucoma. Information regarding the efficacy of TDLCP in paediatric and traumatic glaucoma is still limited. About 20% of patients underwent more than one treatment, to a maximum of four treatments. The treatment performed in a given patient was modulated to minimize trauma without compromising efficacy, which is why we preferred to treat only two quadrants when IOP was < 25 mmHg. When IOP was higher, we did not hesitate to treat larger portions of the ciliary body, up to 270 degrees if necessary. Slit-lamp examination was fundamental to avoid treating thinner areas of the sclera and sites of previous surgery or trauma. With these precautions, we found TDLCP to be relatively safe and effective. No scleral lesions were observed where the laser had been applied and signs of inflammation


after treatment were minimal and subsided rapidly. No phthisis or prolonged hypotonia occurred. The low incidence of severe complications was associated with a low incidence of repeated treatment (22.6%). Other authors have reported repeated treatments in 26–59% of their patients (Bloom et al. 1997; Spencer & Vernon 1999; Schlote et al. 2001). The treatment technique changed slightly during the 3.5 years of the study. Initially, most of the patients received as many as 12 applications to comply with initial study guidelines. During the study, more applications were used in the expectation of a better success rate. Reduction in VA after TDLCP has been reported in 18.7–32.0% of patients and an increase in 10.0–29.0% (Yap-Veloso et al. 1998; Youn et al. 1998; Mistlberger et al. 2001). In our study, VA remained stable after TDLCP in 73.5%, improved in 4.0% and worsened in 22.5% of eyes. The relative simplicity of the technique and its relatively low impact enabled treatment to be carried out on a hospital outpatient basis. This made the experience less stressful for patients and was less costly for the national health service. None of the patients stayed in hospital overnight after treatment. In conclusion, TDLCP was found to be simple, effective and sufficiently safe in controlling IOP in cases of refractory glaucoma. The reduction in IOP also had a positive impact on patient quality of life because it reduced the number of drugs needed and improved eye comfort, even when more than one treatment was necessary. The simplicity of the technique means that social costs are reduced to a minimum.

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Received on December 10th, 2007. Accepted on May 9th, 2008. Correspondence: Gianluca Martone MD Department of Ophthalmology and Neurosurgery University of Siena Viale Bracci 53100 Siena Italy Tel: + 39 0577 585663 Fax: + 39 0577 586162 Email: [email protected]

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