Management of Specific Diseases Oh H, Oshima Y (eds): Microincision Vitrectomy Surgery. Emerging Techniques and Technology. Dev Ophthalmol. Basel, Karger, 2014, vol 54, pp 223–233 (DOI: 10.1159/000360470)

Surgical Management of Retinopathy of Prematurity Michael A. Klufas  · Samir N. Patel  · R.V. Paul Chan  Department of Ophthalmology, Weill Cornell Medical College/NewYork-Presbyterian Hospital, New York, N.Y., USA

Abstract The surgical treatment and management of retinopathy of prematurity (ROP) has evolved significantly over the last decade. The introduction of new techniques, instrumentation, and surgical adjuvants has added to the repertoire of options vitreoretinal surgeons have to treat complex surgical ROP cases. This chapter focuses on a review of the clinical outcomes, indications, techniques, and adjuncts for the surgical treatment of ROP.

laser for treatment-requiring disease, surgical management continues to play a role in the subset of children who develop retinal detachment (RD) despite laser therapy. In spite of improved anatomic outcomes, functional results remain disappointing in many cases, especially for stage 5 disease. This chapter describes the clinical outcomes, indications, techniques, and adjuncts for the surgical treatment of ROP.

© 2014 S. Karger AG, Basel

Pathophysiology

ROP follows a biphasic pattern: from birth to 32 weeks there is suppression of VEGF with relative hyperoxia, and after 32 weeks there is a hypoxiainduced rise in VEGF that leads to abnormal vessel growth. The vasoproliferative drive is diminished by ablation of the ischemic peripheral ­retina. However, the subsequent regressed vasoproliferative cicatricial membranes may induce traction upon the retina that may require incisional surgery. The underlying vitreous traction Downloaded by: Nanyang Technological Univ. 155.69.4.4 - 5/27/2015 3:13:18 AM

The management of advanced retinopathy of prematurity (ROP) has undergone significant strides over the last decade. Major paradigm shifts for the surgical management of ROP have included an evidence-based trend towards lens-sparing vitrectomy (LSV) over scleral buckling (SB), newer microincision vitrectomy instrumentation, and surgical adjuncts including autologous plasmin and anti-vascular endothelial growth factor (VEGF) therapy. Although the management of ROP hinges primarily upon peripheral ablative

Surgical Outcomes

In the Early Treatment of Retinopathy of Prematurity (ETROP) study, despite timely and adequate peripheral laser ablation, initial results showed nearly 1 in 10 infants developed structurally unfavorable outcomes [1, 2]. Although treatment of RD was not specifically part of the ETROP study, eyes with RD were treated at the discretion of the investigator physician. At the 6-year follow-up, among the 401 patients in the ETROP study, 15.2% (63 patients, 89 eyes) experienced RD (40% stage 4A, 20% stage 4B, 13% stage 5, 21% not classified) [1]. Overall, macular reattachment was achieved in 36% of eyes (25/70) with success varying by treatment technique: 34% (17/50) after vitrectomy with or without scleral buckle, 67% (6/9) after SB alone, and 18% with observation only (2/11). Six years after the initial vitreoretinal surgery, macular attachment was seen in 31, 60, and 0% of stage 4A, stage 4B, and stage 5 eyes, respectively. Favorable visual acuity classified as ETDRS visual acuity ≥20/200 was seen in 9% of subjects with RD (6/70 eyes: 5 with stage 4A, 1 unclassified). Among ETROP eyes that developed RD, vitrectomy for stage 4A detachments was not as successful as reported in other single-institution case series [3–7]. This may be explained by variable timing to surgery and physician-dependent factors in a multicenter cohort involving many different vitreoretinal surgeons. Surgical Principles

RD from ROP is complex and surgical management of these unique pediatric cases have evolved over time. One of the overarching principles with ROP surgery to optimize the chance of a success-

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ful outcome is to pursue surgery once neovascular activity wanes and plus disease resolves, which often coincides with the child’s due date [8]. Performing vitrectomy at the peak of the vasoproliferative process may induce bleeding, promote proliferation, and vasoproliferative membrane contraction. Observation until the optimal time for surgery may not be possible in cases of aggressive posterior ROP, which can progress rapidly to RD and continue to have signs of plus disease despite laser therapy. Lens-Sparing Vitrectomy versus Scleral Buckling

Recent clinical studies have favored LSV over SB [4, 9–11]. Good anatomic outcomes after SB for ROP are achieved in approximately 70% of the cases and at the cost of an additional procedure to divide the band, induced myopia/anisometropia, and often poor visual outcomes [3]. A single report of 22 patients with stage 4 ROP found that after a single procedure, LSV was more than twice as effective (72 vs. 31.5%) at achieving retinal attachment at 1 month follow-up [12]. However, at the end of 6 months of follow-up, after one or more procedures there was no difference in the retinal attachment rate between LSV and SB as the first procedure. From a pathophysiology standpoint, SB may have the benefit of supporting the vitreous base and reducing cortical vitreous traction. In ROPrelated detachments, there are tractional forces on the retina which can be difficult to neutralize completely in the setting of a firmly attached posterior hyaloid in children. To further determine the role of SB in reducing tractional forces in ROP-related RD repair, Sears and Sonnie [13] investigated the use of SB in combination with LSV as the initial procedure for stage 4 detachments and found no additional benefit of SB either prior to or at the time of LSV. LSV is an effective and safe technique for RD repair in ROP with a low incidence of complica-

Klufas · Patel · Chan  Oh H, Oshima Y (eds): Microincision Vitrectomy Surgery. Emerging Techniques and Technology. Dev Ophthalmol. Basel, Karger, 2014, vol 54, pp 223–233 (DOI: 10.1159/000360470)

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is thought to be best addressed from a pathophysiologic standpoint with vitrectomy rather than SB.

tions for experienced pediatric vitreoretinal surgeons. Potential complications of vitrectomy ­include endophthalmitis, rhegmatogenous RD, glaucoma, and development of cataract [3]. Following LSV for all types of pediatric conditions, cataract may be seen in approximately 15% of children after this intraocular procedure [14]. Surgical Techniques

Early reports of surgical therapy for eyes with advanced ROP were reported by Machemer and colleagues [15–17], Tasman et al. [18], and Trese [19, 20]. Prior to the surgical technique reported by Maguire and Trese in 1992 [21], lensectomy was routinely performed in infants undergoing vitrectomy. This study described a two-port pars plicata vitrectomy with one instrument serving the dual function of infusion and endoillumination. Ten children 2.5 weeks to 3.75 years of age (median age: 4.25 months) were included, and 5 of these patients had ROP-related detachments [21]. Excluding stage 5 eyes, favorable outcomes were reported [21]. A multitude of other series evaluated the safety and efficacy of LSV for ROP surgery with positive results [3, 5, 7, 22–31], although less impressive results have been reported with progressive posterior-type stage 4A ROP [30] and with stage 5 eyes [29]. Other studies have reported on modified techniques including the use of three-port vitrectomy, smaller-gauge instrumentation [23, 32], and other approaches [33].

ing systems such as the binocular indirect ophthalmic microscope (BIOM) have also been utilized in ROP surgery. Sclerotomies

The distance sclerotomies are placed posterior to the surgical limbus has been investigated and is based upon anatomic properties of the developing eye including growth of the ciliary body and relatively larger crystalline lens in proportion to the vitreous cavity in young children [36, 37]. A useful approximate ‘rule of thumb’ to place sclerotomies for pars plicata vitrectomy in pediatric patients is to have incisions 0.5–1.5 mm posterior to the surgical limbus in neonates (fig. 1). Careful selection and placement of sclerotomies at specific clock hours is also of paramount importance and needs to be tailored to the intraocular pathology in each case. Likewise, surgeon position (superior vs. temporal) is an important consideration preoperatively. Gauge Selection

Vitrectomy gauge selection has varied among studies and is important given the cohesive properties of the pediatric vitreous and unique anatomic constraints in ROP-related RD. Newer instrumentation such as 25+-gauge short (Alcon, Fort Worth, Tex., USA) (fig. 2) and endoscopy are being investigated to benefit surgical management of ROP surgery.

Viewing Systems

Early surgery for aggressive posterior ROP (­APROP), previously known as ‘rush’ disease, has also been suggested to be of benefit [38]. A study by Azuma et al. [38] was undertaken given

Surgical Management of ROP Oh H, Oshima Y (eds): Microincision Vitrectomy Surgery. Emerging Techniques and Technology. Dev Ophthalmol. Basel, Karger, 2014, vol 54, pp 223–233 (DOI: 10.1159/000360470)

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Visualization systems utilized intraoperatively include contact and non-contact systems. In contact systems, special attention is paid to the size of the contact lens [34, 35] so as not to interfere with the more anteriorly placed sclerotomies, given the pediatric ocular anatomy. Non-contact view-

Early Surgery for Aggressive Posterior Retinopathy of Prematurity

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Oh H, Oshima Y (eds): Microincision Vitrectomy Surgery. Emerging Techniques and Technology. Dev Ophthalmol. Basel, Karger, 2014, vol 54, pp 223–233 (DOI: 10.1159/000360470)

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Klufas · Patel · Chan 

stage 4A

32

26

19

56

Singh et al. [31]

Wu et al. [33]

Shah et al. [66]

El Rayes et al. [71]

Kychenthal 13 and Dorta [23]

Sears and 21 Sonnie [13]

stage 4B

11

Choi et al. [30]

LSV

Surgery

stage 4

stage 4A (n = 10), stage 4B (n = 9)

stage 4

stage 4A (n = 23) and 4B (n = 9)

7.1 years

4.6 years

5.6 years

Follow-up

19.1 months

17 months

LSV alone (n = 9) vs. range: LSV + SB (n = 12) 6 months to 5 years

25-gauge LSV

LSV (42.9%) or c 3 years ombined ­vitrectomy and lensectomy (57.1%)

LSV, vitrectomy with lensectomy ± SB

modified 23-gauge 13.9 months vitrectomy

LSV ± SB

progressive LSV posterior-type stage 4A (73% plus disease at time of ­vitrectomy)

stage 4B

13

Choi et al. [29]

Stage

Eyes, n

Study

Table 1. Surgical outcomes in ROP (excluding stage 5)

86% overall – SB added little to success or failure of LSV

92%

73.2% overall (75% LSV)

90% for stage 4A, 44.4% for stage 4B (defined as partial residual RD)

77% achieved reattachment after single operation, 88% after multiple procedures

91% stage 4A, 88% stage 4B

27% attached, 73% TRD at final examination

62%

Anatomic success1

Complications

posterior retinotomy (66.7% in stage 4B, 21.1% overall), dialysis (9.1%), giant retinal tear (3%)

disc dragging (19%), ­cataracts (15%), glaucoma (8%), persistent vitreous hemorrhage (4%), posterior synechia (4%)

not reported

78% of stage 4A fix and follow, 57% of stage 4B fix and follow

not reported

macular hole progressing to inoperable RD (n = 1)

postoperative hypotony with small choroidal detachment that resolved spontaneously

ambulatory vision (VA iatrogenic breaks (4.5%), better than 20/1900) cataract (3.4%), glaucoma achieved in 97.4%, near (32.1%) reading vision (VA better than 20/800) achieved in 42.8%

5 eyes had VA of 6/24 (2: stage 4A, 1: stage 4B), 1 eye 3/50 (stage 4A), 5 eyes HM (3: stage 4A, 2: stage 4B)

not reported

mean logMAR 0.92 for stage 4A, mean logMAR 1.63 for stage 4B

2 eyes with attached cataract, corneal opacity, retina favorable VA, with glaucoma detached retina 68% NLP

3 NLP, 4 LP, 6 form vision corneal opacity, glaucoma, esotropia, retinal break

Visual outcome

Surgical Management of ROP

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Oh H, Oshima Y (eds): Microincision Vitrectomy Surgery. Emerging Techniques and Technology. Dev Ophthalmol. Basel, Karger, 2014, vol 54, pp 223–233 (DOI: 10.1159/000360470)

227

37

40

60

15

Hubbard et al. [5]

Capone et al. [3]

Trese [11]

Noorily et al. [73]

SB

SB

LSV

LSV

LSV (n = 11) vs. SB (n = 16) (first ­procedure)

LSV

25-gauge ­ vitrectomy ± lensectomy

Surgery

10 months

range: 6-40 months

12 months

13 months

last follow-up 6 months

32 months

4.6 months

Follow-up

not reported

Visual outcome

66.67% achieved macular reattachment with single SB procedure

70% stage 4A, 67% stage 4B complete retinal attachment or dry folds

90%

86%: stage 4A 84%, stage 4B 92%

3 eyes fix and follow, 11 eyes LP, 1 eyes NLO

not reported

90% fixation behavior

78% able to fix and follow

when LSV first procedure 72%, not reported when SB first procedure 31%, at last follow-up with a­ dditional procedures there was no difference between LSV first eyes (82%) vs. SB first eyes (69%)

85.2% of eyes were reattached not reported after single LSV, overall 94.4% eyes ultimately achieved at least partial posterior pole ­reattachment, 100% stage 4A, 92.1% stage 4B (partial or complete retinal r­ eattachment)

73% retinal reattachment after one or more surgery at last follow-up

Anatomic success1

1 eye unable to be reattached despite SB and vitreous procedure, 1 eye complicated by lens ­opacification with pupillary block requiring cataract extraction

none reported

2 eyes with glaucoma with edematous corneas and tearing

3 eyes glaucoma, 2 eyes retinal breaks

7 eyes inoperable RDs, 1 eye vitreous hemorrhage

5.6% stage 4B eyes r­ emained detached despite additional procedures – 66.7% of these eyes had intraoperative retinal breaks

vitreous hemorrhage (2 eyes), cataract (1 eye)

Complications

LP = Light perception; NLP = no light perception; TRD = tractional retinal detachment; VA = visual acuity. 1 Complete retinal attachment unless otherwise noted.

stage 4B

stage 4A (n = 27), stage 4B (n = 43)

stage 4A

stage 4A (n = 25), stage 4B (n = 12)

stage 4

27

Hartnett et al. [12]

stage 4A (n = 11), stage 4B (n = 2)

stage 4A (n = 32), stage 4B (n = 76)

13

Gonzalez et al. [26]

Stage

Lakhanpal 108 et al. [72]

Eyes, n

Study

Table 1. Continued

1

2

3

4

Fig. 1. Conjunctival peritomy performed and 23-gauge microvitreoretinal blade used to make sclerotomies approximately 1 mm posterior to the limbus for this 3-port approach. Fig. 2. After preplacement of scleral suture, 25+-gauge (Alcon, Fort Worth, Tex., USA) sutured infusion (3.2 mm) secured in place. Fig. 3. Fluorecein dye from prior fluorescein angiography stains vitreous here. 25+-gauge short vitrectomy cutter used. This length of the 25+-gauge cutter is 18 mm, allowing good access in these smaller neonatal eyes. Fig. 4. All sclerotomies are closed with sutures at the end of the surgery.

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cular tissues, but may also suppress growth of new vessels by removing inflammatory mediators; however it may also decrease abnormal blood vessel growth as traction itself can promote neovascularization. In these neonates at high risk of complications, protocols have been reported to optimize perioperative management by anesthesia [40]. Surgical Adjuncts

Early studies by Blacharski and Charles [41] investigated surgical adjuncts such as thrombin infusion to control hemorrhage during vitrectomy for stage 5 detachments. The use of perfluorocar-

Klufas · Patel · Chan  Oh H, Oshima Y (eds): Microincision Vitrectomy Surgery. Emerging Techniques and Technology. Dev Ophthalmol. Basel, Karger, 2014, vol 54, pp 223–233 (DOI: 10.1159/000360470)

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that retinal photocoagulation, which is effective for less severe forms of ROP, often fails to prevent progressive detachment in APROP. In this series, 22 eyes (15 patients) with APROP underwent vitrectomy with or without lens sparing when retinal photocoagulation failed to prevent continued fibrovascular proliferation. The fovea was well formed in 56% as detected by clinical exam, and a favorable visual outcome (central, steady fixation) was achieved in all but two eyes. A follow-up study from this group on longerterm visual outcomes, found visual acuity ranged from 20/250 to 20/40 in 68.9% of the eyes with successful retinal reattachment [39]. The authors suggest surgical removal of the vitreous scaffold not only reduces tractional forces from fibrovas-

Table 2. Selected surgical outcomes in stage 5 ROP Study

Eyes, n

Stage

Surgery

Follow-up, months

Anatomic success (%)

Visual outcome

Complications

Shah et al. [66]

14

stage V: narrow-narrow (43%), opennarrow (50%), open-open (7%)

LSV, vitrectomy with lensectomy ± SB

32.1

14.3% (reattachment of posterior pole only)

not reported

complete retinal reattachment after stage 5 was seen in only 1 eye which later redetached after 2 years

Wu et al. [50]

80

stage V

autologous or maternal plasmin enzyme-assisted vitreoretinal surgery

49

68.8% (complete zone 1 reattachment of retina)

7.5% (6 eyes) achieved 20/60 to 20/600 vision, 73.8% (59 eyes) worse than 20/600 to LP vision, 13.8% (11 eyes) NLP vision, 5% (4 eyes) uncertain results

reproliferation of fibrovascular tissues (10– 53.3%), glaucoma (7.5%), corneal decompensation (5%), phthisis bulbi (5%), vitreous hemorrhage (5%), band keratopathy (3.8%), papillary membrane (3.5%), cataract (2.5%), conjunctival cyst (1.3%)

Tsukahara et al. [49]

6

stage V: closedclosed (4 eyes), open-open (2 eyes)

vitrectomy with lensectomy and autologous plasmin

range: 11–14

100% reattachment of posterior pole

not reported

none reported

Lakhanpal et al. [74]

33

stage V: openopen (21 eyes), open-narrow (12 eyes)

LSV

48

45.5%, open-open configuration had a statistically significantly higher anatomic success rate than eyes with open-narrow configuration

not reported

intraoperative retinal tears, vitreous haze, ocular hypertension

Lakhanpal et al. [63]

21

stage V

vitrectomy with lensectomy with (11 eyes) or without (10 eyes) intravitreal triamcinolone acetonide

28 (range: 6–42)

28.6%

all 6 eyes that maintained posterior pole attachment were able to fix and follow light

vitreous hemorrhage, phthisis

Gonzales et al. [26]

2

stage V

vitrectomy with lensectomy

4.6

0%

not reported

vitreous hemorrhage, cataract

Gopal et al. [75]

96

stage V

vitrectomy with lensectomy (lens spared in 1 case)

15.8

22.5% (reattachment of posterior pole)

only 2 infants obtained mobile vision

reproliferation and secondary glaucoma

Choi and Yu [76]

38

stage V

vitrectomy with lensectomy (encircling band in 1 case)

24.1

29% (anatomic reattachment of posterior pole) – better success with open funnel type vs. closed funnel type (44.4% vs. 15%)

30% fix and follow vision

18.4% vitreous hemorrhage, 10.5% underwent additional vitrectomy due to persistent TRD

Trese [20]

45

stage V

vitrectomy with lensectomy ± SB

6

45% (anatomic reattachment of posterior pole)

30% functional success

not available

Surgical Management of ROP Oh H, Oshima Y (eds): Microincision Vitrectomy Surgery. Emerging Techniques and Technology. Dev Ophthalmol. Basel, Karger, 2014, vol 54, pp 223–233 (DOI: 10.1159/000360470)

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LP = Light perception; NLP = no light perception; TRD = tractional retinal detachment.

bon intraopertiavely [42, 43] or silicone oil tamponade [44] have been described in surgical reports in the past. More recent advances have focused on the use of enzymatic vitreolysis, perioperative anti-VEGF, and use of other adjuncts such as intravitreal steroids and dyes.

NCT00986362) investigating the safety and efficacy of a single 175-μg dose of ocriplasmin in children (age

Surgical management of retinopathy of prematurity.

The surgical treatment and management of retinopathy of prematurity (ROP) has evolved significantly over the last decade. The introduction of new tech...
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