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Submacular Surgery for Patients with Age-Related Macular Degeneration
P. Kumar Rao and Matthew A. Thomas
Barnes Retina Institute, Washington University, St. Louis, Missouri
I.INTRODUCTION
A.Historical Overview
In the late 1980s initial attempts at surgical removal of choroidal neovasacular membranes (CNVMs) were reported. De Juan and Machemer pioneered a technique that involved performing a vitrectomy followed by a large retinotomy around the macula (1). A retinal flap was reflected, the membrane was removed, the retina was repositioned, and endophotocoagulation was used to create adhesions to hold the retina in place. Unfortunately, poor visual results and the development of proliferative vitreoretinopathy with retinal detachment occurred. In an attempt to limit this complication, Blinder et al. performed scatter photocoagulation outside the vascular arcades prior to surgery (2). Vitrectomy was followed by endodiathermy to the retina just inside the arcades. Again a large flap retinotomy was created, the retina was folded back, the membrane was removed, the retina was once again repositioned, endophotocoagulation was applied to the retinotomy, and silicone oil was injected for prolonged tamponade. Oil removal was performed later, without the development of retinal detachments. These eyes had extensive macular pathology with poor preoperative vision, and visual results remained poor despite the lack of retinal detachments. More recent techniques have enhanced the safety and simplified the procedure.
B.Clinical Relevance/Importance
Vitrectomy techniques may be an appropriate management option for some patients with choroidal neovascularization (CNV) . Current techniques allow safe extraction of most subretinal membranes regardless of etiology but not all patients respond favorably to such an approach. Certain clinical and angiographic characteristics as well as underlying disease processes may allow favorable outcomes. However, no randomized prospective
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data are yet available to prove the role of these procedures. The National Institutes of Health–sponsored Submacular Surgery Trials will determine whether surgery or observation is better for eyes with subfoveal CNV in presumed ocular histoplasmosis syndrome or age-related macular degeneration and in eyes with age-related macular degeneration (AMD)-associated subretinal hemorrhage.
Laser photocoagulation and photodynamic therapy have both been shown to be advantageous over observation in the management of some eyes with AMD-associated subfoveal CNV (3–5). Although the Macular Photocoagulation Study (MPS) demonstrated effective laser treatment for some choroidal neovascular membranes (CNVM) in AMD, 2–5 years after treatment the visual outcome was poor, ranging from 20/100 to 20/400. The rate of persistent or recurrent CNV ranged from 50% to 70% (4,5). Additionally, MPS guidelines exclude many patients from laser treatment (6,7). These limitations have stimulated the search for other therapies.
Surgical excision of subretinal membranes is an alternative to laser treatment, and techniques for surgical removal have become quite safe. Currently there are no randomized prospective clinical trial data available to guide decisions regarding subretinal surgery for CNV. Fortunately the Submacular Surgery Trials (SST) are currently underway and will yield important data regarding this therapy. While recognizing the essential role of the SST, it is of value to review the current state of knowledge of subretinal surgery. This review represents information from retrospective studies, small series, case reports, and personal experience.
C.Patients or Settings Appropriate for Surgery
The best surgical candidates are those patients with type 2 CNV [membranes between the retinal pigment epithelium (RPE) and neurosensory retina] and with extrafoveal ingrowth sites (8–10). Clinically, the appearance of well-defined borders, a thin layer of blood between the membrane and the RPE, pigmented edges, patient age less than 50, and absence of biomicroscopic and stereoscopic fluorescein evidence of elevation of the RPE beyond a well-defined CNVM all suggest that the CNVM is between the RPE and retina (9,11). An anterior location can be determined by finding a rim of blocked fluorescence and absent late staining of surrounding tissues with fluorescein angiography (11). In addition, ocular coherence tomography can help reveal the position of the CNVM and thus help predict which eyes will do well with surgery (12).
Excision of CNVM may be accompanied by loss of underlying RPE. Angiography is often useful in predicting the size of this postoperative defect. This defect is generally greater for patients with AMD than those with multifocal choroidopathies or idiopathic CNVM (13). In AMD the area of the CNVM and the hyperfluorescent halo seen in the late phase of the angiogram before surgery is approximately 80% the size of the postoperative defect.
In many non-AMD eyes, the initial site of presumed ingrowth by the choroidal vessels can be detected preoperatively. The best surgical outcomes are seen with eccentric ingrowth sites (10). Eyes with an unidentifiable ingrowth site probably have more diffuse RPE involvement and may have worse outcomes following surgery. A light colored spot noted during fundus examination may indicate the ingrowth site. Fluorescein angiography may reveal a stalk in the earliest frames or a focal area of hyperfluorescence from which the membrane arises. Such characteristics may allow a preoperative indication for better postoperative outcomes.
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D.Goals of the Procedure
The goal of subretinal membrane removal is to remove the pathological tissue and leave as much RPE and choroid as possible. Prevention of retinal detachment and hemorrhage is also important. Careful selection of the retinotomy site, gentle dissection of the membrane from overlying retina and underlying RPE, and control of intraocular pressure are essential to achieving these goals.
II.DESCRIPTION OF CURRENT TECHNIQUE
In the early 1990s Thomas and Kaplan described the use of a small retinotomy to accomplish CNVM removal (14). The current technique is as follows: complete vitrectomy is followed by removal of the posterior hyaloid (Fig. 1), and a 36-gauge pick is used to pierce the neurosensory retina (Fig. 2). A localized retinal detachment over the CNVM is created by infusing balanced salt solution through the retinotomy using a 33-gauge angled cannula (Fig. 3). The subretinal pick is then reinserted through the retinotomy to separate the neovascular complex from overlying retina and surrounding tissues . Subretinal forceps are then passed through the retinotomy, and the membrane is grasped and removed very slowly, to minimize RPE loss and to allow the retinotomy to stretch around the CNVM (Figs. 4 and 5). Great care is taken to achieve hemeostasis by elevating the intraocular pressure before the membrane is disconnected from the choroid. A gradual return to normal pressure while directly visualizing the excision site allows for immediate recognition of any subretinal bleeding. If any bleeding is seen, the pressure is promptly raised until hemostasis is verified. Once hemostasis is achieved and the intraocular pressure has been returned to normal, the membrane can be removed from the eye.
The intraocular fluid is exchanged for air and residual fluid is removed from the retinotomy site by aspirating just anterior to the retinotomy with a 33-gauge extrusion
Figure 1 The 33-gauge pick (hyaloid lifter) is used to engage posterior cortical vitreous. (From Ryan SJ, ed. Surgical Removal of Subretinal Choroidal Neovascular Membranes in Retina, 3rd ed. St. Louis: Mosby, 2001:2562–2572, Fig. 153-1.)
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Figure 2 The 36-gauge pointed subretinal pick is used to perforate neurosensory retina. One may encounter a slight amount of hemorrhage as the retina is transected. Diathermy is not used. (From Ryan SJ, ed. Surgical Removal of Subretinal Choroidal Neovascular Membranes in Retina, 3rd ed. St. Louis: Mosby, 2001:2562–2572, Fig. 153-2.)
Figure 3 The angled 33-gauge subretinal infusion needle is used to gently infuse balanced salt solution beneath the neurosensory retina. Care is taken not to tear retina at previous laser scars or other adhesions to the underlying membrane. (From Ryan SJ, ed. Surgical Removal of Subretinal Choroidal Neovascular Membranes in Retina, 3rd ed. St. Louis: Mosby, 2001:2562–2572, Fig. 153-3.)
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Figure 4 Current subretinal instruments include (A) a 33-gauge angled infusion needle, (B) an occasionally useful 33-gauge straight cannula, (C) sharpened subretinal picks (for engaging hyaloid, perforating retina, and subretinal work), 33 and 36 gauge, and (D) horizontal subretinal forceps. Additional instruments include subretinal vertical forceps, subretinal horizontal scissors, and subretinal vertical scissors. These latter instruments are only occasionally required. (From Ryan SJ, ed. Surgical Removal of Subretinal Choroidal Neovascular Membranes in Retina, 3rd ed. St. Louis: Mosby, 2001:2562–2572, Fig. 153-4.)
needle. If the retinotomy has not enlarged, fluid is infused until a 10–15% air bubble is left. Face-down postoperative positioning facilitates air tamponade of the retinotomy and prevents cataract formation. These techniques result in a low rate of complications (15,16).
III.CLINICAL OUTCOMES
A.Published Results
1.AMD
Many studies have examined the role of submacular surgery in patients suffering from AMD-related CNVMs. The results are mixed and may reflect the aspect of visual
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Figure 5 The pointed tip of the subretinal pick is used to engage and lift up the neovascular complex, which is subsequently grasped with horizontal forceps. Hemorrhage is prevented by raising the intraocular infusion pressure. (From Ryan SJ, ed. Surgical Removal of Subretinal Choroidal Neovascular Membranes in Retina, 3rd ed. St. Louis: Mosby, 2001:2562–2572, Fig. 153-5.)
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A B
C D
Figures 6 (A) Color photograph of a patient with geographic atrophy and a subretinal neovascular membrane due to age-related macular degeneration. Visual acuity is 20/300. There was no previous laser therapy. (B) Photograph taken 1 month following submacular surgery, revealing some residual subretinal blood at the excision site. (C) Photograph taken 3 years following surgery, revealing RPE and choriocapillary atrophy in the area of preexisting sub retinal neovascular membrane. Visual acuity is 20/200. (D) Photograph taken 7 years following surgery, demonstrating that the area of atrophy has increased in size. Visual acuity is 20/200. See also color insert, Fig. 15.6.
function that is measured. For example, after subretinal membrane removal, patients with AMD may occasionally have residual retinal function in the surgical site when tested with the scanning laser ophthalmoscope (17). Additionally, a recent retrospective case series of surgical removal of subfoveal membranes from patients suffering from AMD demonstrated vision improvement (gained three lines) in 30% or stabilized vision in 42% of surgically treated eyes. Unfortunately, 28% of patients also lost three or more lines of vision. The authors concluded that vision improved or stabilized in the majority of patients. While 72% of patients improved or remained stable, one could also argue that 70% of these patients remained stable or worsened (18).
Previous reports suggest that most patients with AMD do not improve in visual function following surgery (16). Additionally one recent report demonstrates possible
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worsening of visual acuity following surgery and the authors recommend not operating on AMD-associated subfoveal CNVMs (19). Patients with AMD generally do not achieve good vision after surgical excision of subretinal membranes because of the widespread nature of the disease (8,20–24). Another cause for visual decline following surgical treatment may be the loss of perfusion to the underlying choriocapillaris. Preserved perfusion of the choriocapillaris is associated with better postoperative results (25). Unfortunately, the choriocapillaris may continue to atrophy after surgery in patients with macular degeneration. This progressive atrophy may be due to the RPE loss that usually accompanies surgery for subretinal membranes in AMD (26) (Fig. 6).
Many patients with CNVM present with subretinal hemorrhage. Subretinal blood in patients with macular degeneration is often associated with decreased vision if left untreated (27–29). Numerous studies have documented either stabilization or improvement of vision after surgical removal of subretinal hemorrhage (30–34). In addition, evacuation of this blood may result in a smaller scotoma for patients with AMD (35). However, the best candidates for removal of subretinal blood are those who are young and have thick hemorrhages due to causes other than AMD (27,30).
Most of the previously mentioned studies are small series or retrospective reviews. The Submacular Surgery Trials (SST) are a prospective randomized series of studies that are currently enrolling patients and seek to illuminate the potential role this surgical approach may play in managing patients with CNV. The SST pilot study number 1 enrolled 70 patients who had previously received extrafoveal laser photocoagulation for an AMDassociated CNV and then developed subfoveal recurrent neovascularization. This trial was created to test methods and attain an estimate of the number of patients necessary for the larger multicenter trial. The recently published results from this pilot study suggest no reason to prefer surgery over photocoagulation for eyes with recurrent subfoveal CNV associated with AMD. There were few perioperative complications and the size of the surgically affected area was not significantly larger 2 years following surgery than the area of the neovascualar lesion at baseline (36). The SST pilot study number 2 examined qual- ity-of-life outcomes following surgery and laser treatment of recurrent subfoveal CNVM associated with AMD. Of the 70 patients in SST pilot study number 1, 54 were interviewed with the 36-item Short Form Health Survey prior to randomization. At the conclusion of the study, there were no significant differences in quality-of-life outcome scores between the two treatment arms (37).
2.Other Diseases
Surgical treatment of CNVM is most successful in patients with focal abnormalities of the RPE. Patients with presumed ocular histoplasmosis syndrome (POHS), punctate inner choroidopathy, and CNVM formation following focal laser treatment presumably have only focal disturbances of the RPE. Those with myopia and angioid streaks have more diffuse disease, while those with AMD are thought to have widespread RPE disease. Surgery for CNVM in these disorders has variable reported success rates (19,38–42). CNV from idiopathic juxtafoveolar retinal telangiectasis probably should not be approached with our current surgical techniques. The membranes seen in this disease probably arise within the neurosensory retina and only secondarily do they connect to the choroid. Attempted removal has resulted in retinal defects and poor outcomes (43). Children may also develop CNVM from various causes. Our data and a recent report by Sears et al. describe good surgical outcomes for children who develop CNV (44,45). Declining vision, a protracted neurosensory detachment with the development of cystoid macular edema, or subfoveal bleeding may be indications for surgery (44).
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3.Juxtafoveal Membranes
Patients with juxtafoveal membranes may also benefit from surgery. In a study of 35 patients followed for more than 6 months after surgical excision of juxtafoveal membranes of various etiologies, vision improved by three or more lines in 57% of cases. By definition these membranes do not have ingrowth sites beneath the fovea and therefore are likely to have better surgical outcomes (46).
4.Extrafoveal Membranes
Some extrafoveal membranes can be treated with laser according to MPS guidelines. Preservation of overlying retina is probably not as critical with these lesions and laser provides a presumed lower risk alternative to surgery in these cases.
5.Peripapillary Membranes
MPS guidelines do not recommend photocoagulation for membranes larger than 4.5 clockhours adjacent to the temporal half of the optic nerve. In a small series of eyes with peripapillary membranes associated with POHS, 50% of those membranes with subfoveal extension achieved 20/40 vision or better following surgery. Additionally, three peripapillary membranes were strictly extrafoveal and ineligible for laser according to MPS criteria. All three cases achieved 20/20 vision with surgical excision (47). These are encouraging results for surgical treatment of large peripapillary membranes.
B.Complications
Complications can occur both during and after surgery. Intraoperative complications include those potentially associated with any pars plana vitrectomy, such as retinal tears or detachment, and bleeding. Intraoperative complications unique to this surgery include enlarged retinotomy sites with persistent subretial fluid or detachment, extensive subretinal hemorrhage, and large RPE defects. Delayed complications may include cataract formation, retinal detachment, and recurrent membrane formation. Recurrence of CNV after surgical removal of subretinal membranes has been reported to occur in 23–52% of cases (15,48). Melberg et al. found that when CNV recurred following surgery, the best visual outcomes were achieved for patients who underwent laser treatment for an extrafoveal recurrence (49). Benson et al. have noted that repeat surgery was not associated with worse visual outcome (48). Photodynamic therapy may also play a role in controlling recurrences. Recurrent membranes should be treated with laser if extrafoveal and with either laser photocoagulation or repeat surgery if juxtafoveal and with either repeat surgery, photodynamic therapy, or observation if the regrowth is central.
IV. FUTURE DEVELOPMENTS
The current surgical technique will undoubtedly evolve and improve, aided by further refinements in instrumentation (50). Photodynamic therapy offers another treatment option for some patients suffering from subretinal membranes. This therapy may prove especially useful for those patients who have recurrent CNV after subretinal surgery. The ongoing Submacular Surgery Trials will further define which patients, if any, will benefit from subretinal surgery. Ultimately, pharmacological agents will help prevent and/or inhibit CNV.
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V.SUMMARY
Choroidal neovascularization can cause severe visual disturbances. Current management options include observation, laser photocoagulation, photodynamic therapy, and surgical excision. Current guidelines for laser therapy have been well established but exclude many patients. Photodynamic therapy may hold some promise but its value is limited by the need for repeated treatments. An alternative therapy for patients with subretinal membranes may be surgical removal.
The Submacular Surgery Trials seek to clarify the role of vitreous surgery in the management of CNV and are currently enrolling patients in all three arms: SST-H (subfoveal CNV associated with POHS and/or idiopathic cause), SST-N (AMD-associated CNV with at least some classic component and no prior laser therapy), and SST-B (large hematomas). The trials will determine whether patients with AMD and large subfoveal membranes that do not fit MPS guidelines or subfoveal hemorrhage have better outcomes following surgical excision or observation. Additionally, they will compare surgical outcomes to observation for patients with CNV from the presumed ocular histoplasmosis syndrome and idiopathic causes.
Excision of choroidal neovascular membranes is technically possible and safe. The best candidates are those with membranes between the RPE and retina (type 2 membranes). A small retinotomy, gentle dissection, and pressure tamponade are critical to the technique. The Submacular Surgery Trials will help determine which patients will benefit from surgery.
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