Surgical Removal of CNV
Choroidal neovascularization may require surgical intervention, particularly when it is not a result of AMD.
Maurizio Battaglia Parodi, MD • Ilaria Zucchiatti • Maria Lucia Cascavilla, MD • Francesco Bandello, MD, FEBO
Choroidal neovascularization represents a nonspecific response to a variety of chorioretinal diseases. According to the anatomical features, three main CNV growth patterns can be identified: sub-retinal pigment epithelium (type 1), subretinal (type 2) and intraretinal (type 3). Many treatment approaches have been tried over the past decade; overall, surgical excision has been shown to be more effective in eyes presenting non–AMD-related CNV, which are frequently type 2 CNVs. The purpose of this review is to provide a synopsis of the surgical management of CNV related to different diseases.
Surgical management of AMD has been studied using different techniques: submacular surgery,3 pneumatic displacement of submacular blood with or without intravitreal tissue plasminogen activator (TPA), subretinal injection of TPA4,5 and macular translocation.6,7
Submacular surgery was first described by de Juan3 as a technique for excision of submacular scars in AMD. A three-port pars plana vitrectomy with or without posterior hyaloid removal is performed, followed by a posterior retinotomy, optional infusion of subretinal balanced salt solution, and mobilization and removal of the CNV. Several surgeons complete the procedure with RPE transplant under the fovea. A recent review8 analyzed the effectiveness of submacular surgery, considering three studies: two multicenter trials with a similar design, comparing submacular surgery vs observation,9,10 and a third pilot study that compared surgery and photocoagulation laser.11 The two larger studies9,10 were conducted between 1997 and 2003 by the same research group that had compared sub-macular surgery and observation in two different populations, with9 (SST 2004 Group B; 336 patients randomized) and without10 (SST 2004 Group N; 454 patients randomized) blood.
The multifactorial causes of CNV: (a) VEGF, (b) VEGF bound to VEGF receptor, (c) formation of neovasculature, and (d) extravasation of inflammatory cells.
No difference was found between macular surgery and observation regarding visual loss or gain of at least two lines at one year. Neither contrast threshold nor reading speed showed meaningful benefit with surgery, although quality of life (expressed by NEI-VFQ questionnaire score) turned out to be better in treated patients. Major risks related to submacular surgery included cataract and retinal detachment development.
Another pilot study11 randomizing 70 patients either to submacular surgery or to photocoagulation revealed that no functional difference or difference in NEI-VFQ questionnaire results could be registered, whereas important complications occurred in the surgery arm, including cataract and retinal detachment.
Pneumatic displacement of submacular hemorrhage has been reported as a treatment for visual recovery of patients with hemorrhagic CNV.12,13 Surgical technique might rely on several options, including injection of gas,14,15 TPA,16 TPA and gas,17–20 subretinal TPA with displacement by perfluorocarbon liquid,21 subretinal TPA followed by hemorrhage evacuation,22,23 vitrectomy with intravitreal TPA and intraocular gas bubble,24 and vitrectomy with subretinal TPA combined with a gas bubble.25,26 Overall, mere pneumatic displacement with or without TPA leads to limited functional results,27 although no clinical trial data are currently available.
Vitrectomy with hemorrhage-CNV complex removal offers better visual results than simple subretinal hemorrhage displacement.12 A retrospective case series28 with 15 eyes affected by massive subretinal hemorrhage showed that surgery was associated with a modest visual improvement up to one year postoperatively. Anti-VEGF agents, such as bevacizumab (Avastin, Genentech) and ranibizumab (Lucentis, Genentech), have been combined with gas injection.29,30
Another surgical approach is represented by macular translocation surgery, in which the retina is completely detached from the RPE and, after CNV removal, is rotated around the optic nerve and the fovea and shifted upwards. Then, the retina is reattached with silicone oil tamponade. Later, extraocular muscle surgery is performed and the globe is rotated the other way around. Macular translocation surgery is a complex procedure, and numerous complications have been reported, including retinal breaks and detachment, macular holes, macular fold, intraocular hemorrhages and CNV recurrence. As yet, no data from randomized clinical trials are available. A study of 50 patients comparing full macular translocation with photodynamic therapy in predominantly classic subfoveal CNV showed no difference in visual loss of three or more lines, nor in the mean change of contrast sensitivity and rate of recurrence of CNV.31
Surgical approaches for myopic CNV may consist of sub-macular surgery and macular translocation surgery. The technique for CNV surgical removal currently used is similar to that described by Thomas in 1991.32 After central vitreous removal and separation of the posterior hyaloid, a fine cannula is used to make a retinotomy away from the foveal center, and then the CNV membrane is grasped and extracted after separation from neurosensory retina and RPE by injection of balanced saline solution.
Submacular surgery for myopic CNV has been evaluated in several studies with differing outcomes.33–35 Bottoni reported that VA improved by at least two lines in 45% and underwent a functional stabilization in 37% of 65 eyes with subfoveal myopic CNV after a mean 16-month follow-up.33 Uemera obtained a VA improvement in 39% and a stabilization in 26% in 48 eyes with subfoveal myopic CNV over a mean follow-up of 24 months.10 In a study by Ruiz-Moreno, no significant change in VA was observed in 22 patients who had removal of myopic CNV after a mean 29-month follow-up.
Macular translocation techniques have been applied to myopic CNV, both as limited macular translocation (LMT)36 and macular translocation with 360° retinotomy (MT 360).37 LMT is usually performed by means of mattress sutures through the sclera. To increase the macular displacement, a two-fold suture is realized. Three-port pars plana vitrectomy is then performed, and balanced-saline solution is injected into the subretinal space to obtain a retinal detachment. Once the sensory retina is detached at the posterior pole and in the temporal quadrants, the preplaced scleral sutures are tied, imbricating the sclera.
A study comparing visual outcomes of LMT and surgical removal of subfoveal CNV described a visual benefit in eyes treated with LMT, although the CNV recurrence rate was high.38 Another investigation comparing VA results from LMT for CNV secondary to AMD and degenerative myopia revealed a better prognosis for myopic CNV.39 MT 360 for myopic eyes has been performed by some authors, but the results of this approach are still controversial, bearing in mind the possible complications in myopic eyes.40,41
CNV OF OTHER ETIOLOGIES
Surgical excision of CNV has been performed in many other diseases (Table 1). Although there are no data from randomized clinical trials comparing surgical outcome to natural history and knowledge about anatomical and functional outcomes is based on limited case series, selected cases of non-AMD and nonmyopic CNVs can benefit from surgical excision.
In general, CNV excision seems to be beneficial for patients less than 50 years old. This finding may be related to the characteristics of CNV in younger patients, which is more frequently a type 2 CNV. Indeed, RPE damage related to surgical removal of CNV type 1 leads to an irreversible choriocapillary atrophy, with consequent VA loss, whereas RPE impairment due to type 2 CNV removal is more limited.42
Recurrence of CNV after surgery represents a major cause of poor long-term visual outcomes. Recurrence rates ranging from 37% to 44% have been registered after surgical excision of subfoveal CNV in presumed ocular histoplasmosis syndrome,43–45 and from 11% to 66% in CNV caused by multifocal choroiditis, pathologic myopia and unknown etiologies.46,47
The role of surgery in the treatment of CNV remains controversial. At present, there is no clear evidence of benefit from surgical management of AMD-related CNV. A potential benefit may derive from surgical approaches to extensive macular hemorrhage due to CNV. As for non-AMD diseases, even in the absence of data from randomized clinical trials, a surgical option may be considered, in younger patients especially and in cases presenting extensive subretinal hemorrhage and non-responders to anti-VEGF therapy. It is also possible that functional results from surgical management may improve if CNV excision can be combined with other techniques, such as transplantation of RPE or iris pigment epithelium, or with specific anti-VEGF therapy. RP
1. De Juan E Jr, Loewenstein A, Bressler NM, Alexander J. Translocation of the retina for management of subfoveal choroidal neovascularization II: a preliminary report in humans. Am J Ophthalmol. 1998;125:635–646.
2. Haupert CL, McCuen BW 2nd, Jaffe GJ, et al. Pars plana vitrectomy, subretinal injection of tissue plasminogen activator, and fluid-gas exchange for displacement of thick submacular hemorrhage in age-related macular degeneration. Am J Ophthalmol. 2001;131:208–215.
3. Herriot WJ. Further experience in management of submacular hemorrhage with intravitreal t-PA. Paper presented at: American Academy of Ophthalmology annual meeting; Oct 26–29, 1997; San Francisco, CA.
4. Machemer R, Steinhorst UH. Retinal separation, retinotomy and macular relocation: I. Experimental studies in the rabbit eye. Graefes Arch Clin Exper Ophthalmol. 1993;231:629–634.
5. Eandi CM, Giansanti F, Virgili G. Macular translocation for neovascular age-related macular degeneration (Review). 2009. The Cochrane Collaboration.
6. Giansanti F, Eandi CM, Virgili G. Submacular surgery for choroidal neovascular-isation secondary to age-related macular degeneration. Cochrane Database Syst Rev. 2008;4:CD006928.
7. Bressler NM, Bressler SB, Childs AL, et al. Submacular Surgery Trials (SST)Research Group. Surgery for hemorrhagic choroidal neovascular lesions of age-related macular degeneration: ophthalmic findings: SST report no. 13. Ophthalmology. 2004;111:1993–2006.
8. Hawkins BS, Bressler NM, Misaka PH, et al. Submacular Surgery Trials (SST) Research Group. Surgery for subfoveal choroidal neovascularization in age-related macular degeneration: ophthalmic findings: SST report no. 11. Ophthalmology.
9. Submacular surgery trials randomized pilot trial of laser photocoagulation versus surgery for recurrent choroidal neovascularization secondary to age-related macular degeneration: II. Quality of life outcomes submacular surgery trials pilot study report number 2. Am J Ophthalmol. 2000;130:408–418.
10. Bressler NM, Bressler SB, Hawkins BS, et al. Submacular surgery trials randomized pilot trial of laser photocoagulation versus surgery for recurrent choroidal neovascularization secondary to age-related macular degeneration: I Ophthalmic outcomes submacular surgery trials pilot study report number 1. Am J Ophthalmol. 2000;130:387–407.
11. Thompson JT, Sjaarda RN. Vitrectomy for the treatment of submacular hemorrhages from macular degeneration: A comparison of submacular hemorrhage/ membrane removal and submacular tissue plasminogen activator-assisted pneumatic displacement. Trans Am Ophthalmol Soc. 2005;103:98–107.
12. Scheider A, Gundisch O, Kampik A. Surgical extraction of subfoveal choroidal new vessels and submacular haemorrhage in age-related macular degeneration: results of a prospective study. Graefes Arch Clin Exp Ophthalmol. 1999;237:10–15.
13. Daneshvar H, Kertes PJ, Leonard BC, et al. Management of submacular hemorrhage with intravitreal sulfur hexafluoride: a pilot study. Can J Ophthalmol. 1999;34:385–388.
14. Ohji M, Saito Y, Hayashi A, et al. Pneumatic displacement of subretinal hemorrhage without tissue plasminogen activator. Arch Ophthalmol. 1998;116:1326–1332.
15. Chaudhry NA, Mieler WF, Han DP, et al. Preoperative use of tissue plasminogen activator for large submacular hemorrhage. Ophthalmic Surg Lasers. 1999;30:176–180.
16. Schulze SD, Hesse L. Tissue plasminogen activator plus gas injection in patients with subretinal hemorrhage caused by age-related macular degeneration: predictive variables for visual outcome. Graefes Arch Clin Exp Ophthalmol. 2002;240:717–720.
17. Hattenbach LO, Brieden M, Koch F, et al. Intravitreal injection of rt-PA and gas in the management of minor submacular haemorrhages secondary to age-related macular degeneration. Klin Monatsbl Augenheilkd. 2002;219:512–518.
18. Handwerger BA, Blodi BA, Chandra SR, et al. Treatment of submacular hemorrhage with low-dose intravitreal tissue plasminogen activator injection and pneumatic displacement. Arch Ophthalmol. 2001;119:28–32.
19. Krepler K, Kruger A, Tittl M, et al. Intravitreal injection of tissue plasminogen activator and gas in subretinal hemorrhage caused by age-related macular degeneration. Retina. 2000;20:251–256.
20. Hesse L, Schmidt J, Kroll P. Management of acute submacular hemorrhage using recombinant tissue plasminogen activator and gas. Graefes Arch Clin Exp Ophthalmol. 1999;237:273–277.
21. Kamei M, Tano Y, Maeno T, et al. Surgical removal of submacular hemorrhage using tissue plasminogen activator and perfluorocarbon liquid. Am J Ophthalmol. 1996;121:267–275.
22. Moriarty AP, McAllister IL, Constable IJ. Initial clinical experience with tissue plasminogen activator (tPA) assisted removal of submacular haemorrhage. Eye. 1995;9:582–588.
23. Lewis H. Intraoperative fibrinolysis of submacular hemorrhage with tissue plas-minogen activator and surgical drainage. Am J Ophthalmol. 1994;118:559–568.
24. Tsai SC, Lin JM, Chen HY. Intravitreous recombinant tissue plasminogen activator and gas to treat submacular hemorrhage in age-related macular degeneration. Kaohsiung J Med Sci. 2003:19:608–616.
25. Olivier S, Chow DR, Packo KH, et al. Subretinal recombinant tissue plasmino-gen activator injection and pneumatic displacement of thick submacular hemorrhage in age-related macular degeneration. Ophthalmology. 2004;111:1201–1208.
26. Haupert CL, McCuen BW 2nd Jaffe GJ, et al. Pars plana vitrectomy, subretinal injection of tissue plasminogen activator, and fluid-gas exchange for displacement of thick submacular hemorrhage in age-related macular degeneration. Am J Ophthalmol. 2001;131:208–215.
27. Gopalakrihan M, Giridhar A, Bhat S, et al. Pneumatic displacement of sub-macular hemorrhage: Safety, efficacy, and patient selection. Retina. 2007;27:329–334.
28. Fine HF, Iranmanesh R, Del Priore LV, et al. Surgical outcomes after massive subretinal hemorrhage secondary to age-related macular degeneration. Retina. 2010;30:1588–1594.
29. Chawla S, Misra V, Khemchandani M. Pneumatic displacement and intravitreal bevacizumab: A new approach for management of submacular hemorrhage in choroidal neovascular membrane. Ind J Ophthalmol. 2009;57:155–157.
30. Sandhu SS, Manvikar S, Steel DH. Displacement of submacular hemorrhage associated with age-related macular degeneration using vitrectomy and sub-macular tPA injection followed by intravitreal ranibizumab. Clin Ophthalmol.
2010 Jul 21;4:637–642.
31. Gelisken F, Voelker M, Schwabe R, et al. Full macular translocation versus photodynamic therapy with verteporfin in the treatment of neovascular age-related macular degeneration: 1-year results of a prospective, controlled, randomized pilot trial (FMT-PDT). Graefes Arch Clin Exp Ophthalmol. 2007;245:1085–95.
32. Thomas MA, Dickinson JD, Melberg NS, et al. Visual results after surgical removal of subfoveal choroidal neovascular membranes. Ophtalmology. 1994;101:1384–1396.
33. Bottoni F, Perego E, Airaghi P, et al. Surgical removal of subfoveal choroidal neovascular membranes in high myopia. Graefes Arch Clin Exp Ophthalmol. 1999;237:573–582.
34. Uemera A, Thomas MA. Subretinal surgery for choroidal neovascularisation in patients with high myopia. Arch Ophtalmol. 2000;118:344–350.
35. Ruiz-Moreno JM, De la Vega C. Surgical removal of subfoveal choroidal neovascu-larisation in highly myopic patients. Br J Ophtalmology. 2001;85:1041–1043.
36. Fujikado T, Ohji M, Saito Y, et al. Visual function after foveal translocation with scleral shortening In patients with myopic neovascular maculophaty. Am J Ophtalmol. 1998;125:647–656.
37. Glacet-Bernard A, Simon P, Hamelin N, et al. Translocation of the macula for management of subfoveal choroidal neovascularization: comparison of results in age related macular degeneration and degenerative myopia. Am J Ophtalmol. 2001;131:78–79.
38. Hamelin N, Glacet-Bernard, Brindeau C, et al. Surgical treatment of subfoveal neovascularization in myopia: macular traslocation bs surgical removal. Am J Ophtalmol. 2002;133:530–536.
39. Glacet-Bernard A, Simon P, Hamelin N, et al. Translocation of the macula for management of subfoveal choroidal neovascularization: comparison of results in age related macular degeneration and degenerative myopia. Am J Ophtalmol. 2001;131:78–79.
40. Fujikado T, Ohji M, Kusaka S, et al. Visual function after foveal translocation with 360-degree retinotomy and simultaneous torsional muscle surgery in patients with myopic neovascular maculopathy. Am J Ophthalmol. 2001;131:101–110.
41. Yamada Y, Miyamura N, Suzuma K, Kitaoka T Long-term Follow-up of Full Macular Translocation of Choroidal Neovascularization. Am J Ophthalmol. 2010;149:453–457.
42. Berglin L, Algvere P, Olivestedt G, et al. The Swedish national survey of surgical excision for submacular choroidal neovascularization (CNV). Acta Ophthalmol Scand. 2001;79:580–4.
43. Thomas MA, Dickinson JD, Melberg NS, et al. Visual results after surgical removal of subfoveal choroidal neovascular membranes. Ophthalmology. 1994;101:1384–1396.
44. Berger AS, Conway M, Del Priore LV, et al. Submacular surgery for subfoveal choroidal neovascular membranes in patients with presumed ocular histoplas-mosis. Arch Ophthalmol. 1997;115:991–996.
45. Melberg NS, Thomas MA, Dickinson JD, Valluri S. Managing recurrent neovas-cularization after subfoveal surgery in presumed ocular histoplasmosis syndrome. Ophthalmology. 1996;103:1064–1068.
46. Eckstein M, Wells JA, Aylward B, Gregor Z. Surgical removal of non-age-related choroidal neovascular membranes. Eye. 1998;12:775–780.
47. Melberg NS, Thomas MA, Burgess DB. The surgical removal of subfoveal choroidal neovascularization. Ingrowth site as a predictor of visual outcome.Retina. 1996;16:190–195.
|Maurizio Battaglia Parodi, MD, Ilaria Zucchiatti, Maria Lucia Cascavilla, MD, and Francesco Bandello, MD, FEBO, all serve on the faculty in the department of ophthalmology at University Vita-Salute, Scientific Institute San Raffaele in Milan. None of the authors report any financial interest in any products mentioned in this article. Dr. Parodi can be reached via e-mail at firstname.lastname@example.org|