Abstract
purpose. To compare the long-term outcomes of macular translocation (MT) and autologous RPE–choroid patch graft (PG) in patients with neovascular age-related macular degeneration (AMD).
methods. This is a retrospective review of the first 12 patients who underwent MT and the first 12 patients who underwent PG. Visual acuity (VA), contrast sensitivity (CS), clinical findings, and complications were recorded. Microperimetry and fundus imaging were reviewed. Outcome measures were the change in VA and CS over 3 years in each group and rates of complication. Microperimetry and fixation in three best cases from each group were described.
results. The two groups were matched for age and VA. Median follow-up durations were 41 (MT) and 38 (PG) months. Median VA (logMAR) was maintained in the MT group: 0.90 at baseline and 0.69 at 3 years (P = 0.09) whereas in the PG group, median VA declined from 0.87 to 1.38 at 3 years (P < 0.001). Both surgical modalities had high rates of detachment and macular edema. Although more extensive RPE damage occurred in PG, the graft resisted growth of recurrent choroidal neovascularization toward the fovea. Near normal VA was achievable by each technique but macular sensitivity and fixation stability were superior in the MT group.
conclusions. In the present cohort, MT maintained VA for 3 years but PG did not. This outcome may be related to the differences in surgical approach, source of RPE, and choroidal perfusion. The authors recommend MT in preference to PG for treatment of patients with the second eye affected by neovascular AMD unsuitable for other treatment.
Age-related macular degeneration (AMD) is a disease that primarily involves the retinal pigment epithelium (RPE), Bruch’s membrane, and the choroidal circulation resulting in secondary loss of retinal function.
1 Choroidal neovascularization (CNV) is a devastating complication that can now be treated using anti-vascular endothelial growth factor (anti-VEGF) agents. However, treatment of patients who present with or subsequently develop massive submacular hemorrhage, RPE tear, or geographic atrophy (GA) remains controversial. Surgical reconstruction of the submacular space, or maculoplasty may be an option for these patients.
2
Concepts in surgical treatment for neovascular age-related macular degeneration (AMD) have evolved over the past two decades.
3 At its conception, the intent of surgery was similar to those of nonsurgical approaches such as laser photocoagulation, photodynamic therapy (PDT), and anti-VEGF agents, in that they either removed, ablated, or induced regression of the CNV.
4 5 6 However, macular translocation with 360° retinotomy (MT) and autologous RPE–choroid patch graft (PG) have been investigated as an alternative approach to treatment of the residual effect in the submacular RPE and choroid after removal of CNV.
7 8 9 10 Aisenbrey et al.
11 reported the long-term outcomes (mean follow-up of 38.2 months) after MT, with three quarters of eyes losing fewer than three lines. MacLaren et al.
12 reported long-term survival of macular PG in four patients, although they had loss of fixation and autofluorescence signal over the grafts after 5 years. Instead of harvesting PG from the macular region, van Meurs and Van Den Biesen
10 described a modified technique of using equatorial PG to reconstruct submacular RPE defect. The same group reported a slightly higher rate of vision stabilization and improvement after PG surgery in the 11 patients who were observed for 4 years.
13 However, there has been no report comparing the long-term outcomes and quality of visual function between MT and equatorial PG when performed in the same center by the same surgeon.
We have reported the 6-month to 1-year outcome of MT in 26 patients and equatorial PG in 12 patients from our institution.
14 15 In this study, we sought to compare the 3-year outcomes after the use of these two surgical techniques. To explore the best possible visual outcome, we also describe the quality of vision, measured by detailed microperimetry, in the three best cases from each group.
The medical charts from the first 12 patients who underwent MT (from May 2003 to April 2005) and the first 12 patients who underwent PG (from August 2004 to June 2005) were reviewed. At the time of enrollment, anti-VEGF therapy was not available, and PDT was indicated only for treatment of predominantly classic lesions, as outlined by the National Institute for Health and Clinical Excellence of the United Kingdom. This research adhered to the tenets of the Declaration of Helsinki and was approved by our institutional review board, the Research Governance Committee of Moorfields Eye Hospital. All patients gave consent to participate in the original pilot studies in MT and PG surgery, which were previously approved by the Ethics Committee.
The surgical techniques of MT and PG are similar to those described previously.
8 10 16 All surgical procedures were performed by the same author (LDC) except for three PGs, which were performed by another author (GWA).
In brief, MT surgery began with phacoemulsification with intraocular lens (IOL) implant, followed by vitrectomy, detachment of the posterior hyaloid and vitreous base shaving. Retinal detachment was induced using a flexible, dual-bore 41-gauge cannula (1270.0.100; Synergetics, St. Louis, MO) and extended to total detachment by two or three air–fluid exchanges. After a 360° retinotomy was created with the vitreous cutter, the temporal retina was flapped over the disc, nasally, with Eckardt ring-end forceps (1286-QM; DORC, Zuidland, The Netherlands) to allow removal of the CNV and any subretinal blood. A small bubble of perfluoro-n-octane heavy liquid (Perfluoron; Alcon Laboratories Inc., Fort Worth, TX) was then placed onto the disc to flatten the posterior pole. A Tano stiff diamond-dusted membrane scraper (model 20.07; Synergetics) was used to grip the retinal surface and rotate the fovea away from the RPE defect. The entire vitreous cavity was filled with heavy liquid followed by a 360° laser retinopexy. Heavy liquid was then directly exchanged for silicone oil. Two months after MT a combined counterrotation surgery and removal of silicone oil was performed.
For PG surgery, we performed vitrectomy, separation of the hyaloid and removal of CNV through a superonasal or superotemporal macular retinotomy. The donor site, at the superior equator, was first surrounded with contiguous argon laser photocoagulation and the graft was then cut out with vertical scissors and separated from the sclera. While the graft was grasped on the choroidal side by a specialized aspirating reflux spatula, the retina was peeled off and the remaining RPE–choroid patch inserted into the submacular space. The macular bleb detachment was then flattened with perfluoro-n-octane liquid which also facilitated the release of PG from the spatula. After laser retinopexy around the donor site, the eye was filled with silicone oil. Two months later, the patients underwent combined phacoemulsification, silicone oil removal, and IOL implant.
The main outcome measure was recorded best corrected visual acuity (VA) at baseline and 1, 2, and 3 years after surgery. Secondary outcome measures included contrast sensitivity (CS) and anatomic status of the retina, macula, and RPE.
We reviewed the documented clinical findings, fundus angiographies, and autofluorescence and optical coherence tomography (OCT) images to determine whether there was atrophy of the retina and RPE, macular edema, or recurrent CNV. The last observation carried forward method was required for the 3-year VA and CS data in two patients from each group. Three cases with the best VA from each group were chosen for further descriptive analysis of fixation and retinal sensitivity derived from microperimetry.
Best corrected VA measurements from the Early Treatment of Diabetic Retinopathy Study (ETDRS) chart or the Snellen chart were converted to logarithm of the minimum angle of resolution (logMAR) for analysis.
19 CS was measured on the Pelli-Robson chart at 1 m and expressed as the logarithm of CS (logCS).
20 Clinical documentation of epiretinal membrane, macular edema, CNV, and retina–RPE atrophy were noted and confirmed by review of fundus imaging. Fundus color photography was performed (TRC-50 IA/IMAGEnet H1024 system; Topcon, Tokyo, Japan), and OCT was acquired (StratusOCT, software ver. 4.0; Carl Zeiss Meditec, Inc., Dublin, CA, or the 3D OCT-1000, software version 2.12; Topcon). The status of the RPE was examined by using fundus autofluorescence and captured with a scanning laser ophthalmoscope (SLO; Heidelberg Retina Angiograph II [HRA II], Heidelberg Engineering GmbH, Dossenheim, Germany).
A microperimeter (MP-1; Nidek Technologies, Padova, Italy) was also used for assessment of fixation stability and retinal sensitivity in selected patients. A fixation test was performed with a 1° white cross fixation target, with the patient instructed to look at the center of the cross. A 30-second recording of fixation loci was made and stability was quantified in two ways: by the proportion of fixation points within 2° from the gravitational center of all fixation points as proposed by Fuji et al.
21 or by the bivariate contour ellipse area (BCEA) as described by Steinman.
22 23 Blink artifacts, seen as isolated large fixation deviation from the gravitational center in the fixation time profile graph provided by the software (NAVIS, ver. 1.7.2; Nidek), were removed to allow calculation of BCEA. Microperimetry was performed with manually customized and preset test grids, 4-2 staircase strategy and Goldmann III size stimulus of 200-ms duration. The local defect map provided by the software was used for analysis. Mean sensitivity within central 10° and 20° were calculated. The local defect map was overlaid and correlated with autofluorescence images.
Baseline characteristics were compared between the MT and PG groups with the Fisher exact test (sex, lesion type) and Mann-Whitney U test (age, duration of symptoms, lesions size, VA, and CS). Change in VA and CS between baseline and follow up visits were analyzed with the nonparametric repeated-measures Friedman test. Data were analyzed with commercial software (Statistical Package for the Social Sciences, ver. 14.0; SPSS, Inc., Chicago, IL). P < 0.05 was considered statistically significant.
MT surgery was combined with phacoemulsification and intraocular lens (IOL) implant in 11 patients. Chorioretinal adhesion at the macula precluded translocation in two patients. The remaining nine patients had 45° to 60° of foveal rotation without any complication. Combined globe counterrotation (10/12) and removal of oil (11/12) was performed a median of 12 weeks after MT. Residual oil required further surgery in three patients and the median time to final removal of oil was 15 weeks. In two patients, residual torsion of greater than 30° required further extraocular muscle surgery at ∼9 months.
PG surgery was performed in 11 phakic eyes. We found that 9 of 12 had CNV removal in one piece, 11 of 12 had insertion of graft in one move, 3 of 12 had no submacular manipulation, 5 of 12 had two or more manipulations of the graft, and none had significant submacular choroidal hemorrhage. One patient had intraoperative giant retinal tear. Combined phacoemulsification (11/12) and removal of oil and the IOL implant were performed a median of 17 weeks after PG. However, in three patients, oil was reinjected for repair of retinal detachment and removed at 6 and 22 months later in two patients, respectively.
The retina was attached at 1 year in all 24 patients. However, within the first year, three patients in the MT group had three detachments under the oil that were repaired, and the retina remained attached after removal of oil. In the PG group, four patients had detachments that required six surgical repairs, and one had an inferotemporal U-tear with limited subretinal fluid, which was treated with laser retinopexy. No further retinal detachment occurred after 1 year, although one patient in each group still had oil tamponade at 45 (PG) and 48 (MT) months.
All 24 patients had postoperative serial OCT and fundus autofluorescence imaging for correlation with clinical findings.
In the MT group, clinical and OCT assessments of the macula at 1 year revealed no retinal thickening, intraretinal cysts, subretinal fluid, or subretinal tissue in 6 of 12 eyes. However, one developed a full-thickness macular hole and two showed small intraretinal cystic changes on OCT after 2 years. In the other six eyes, large intraretinal cysts were present, of which, two had insufficient or no foveal rotation, two were related to CNV detected at 2 to 3 months after MT, and two were associated with dense epiretinal membranes that developed at 6 to 7 months after MT. In the latter two patients, edema did not resolve despite peeling of the membranes. Overall, four patients had residual or recurrent CNV, all detected within the first 3 months.
In the PG group, all patients had distorted outer retinal structure due to the irregular RPE surface of the graft
(Fig. 2) . Although foveal depression was seen in 6 patients, all 12 had cystic changes in the retina over the graft accompanied by various amounts of atrophy and thickening. Overall, four patients developed recurrent CNV (2 within 1 year and 2 after 1 year). None of the recurrent CNV invaded the PG. All grafts also had focal hyperpigmentation which became darker over time. Donor sites were free from any CNV during follow-up.
The intensity of autofluorescence in the foveal region did not appear to change over time but the size of RPE defect (at the inferior arcade after MT or surrounding the entire PG) enlarged
(Fig. 2) . Loss of autofluorescence around the PG was prominent in all cases of PG
(Fig. 2) .