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• W2051237447 abstract "Purpose: A free autologous retinal pigment epithelium (RPE)–choroid graft can be harvested during transplantation surgery from a 6 or 12 o’clock site in the midperiphery. This study evaluated whether proliferative vitreoretinopathy (PVR) occurs more frequently in patients with an inferior donor site retinotomy, which is not closed by the tamponade and is in contact with the hydrophilic, pro-inflammatory and fibrotic environment, than in patients with a superior donor site retinotomy. Methods: Retrospective analysis of a prospective cohort of 246 patients with exudative age-related macular degeneration treated with an RPE–choroid graft transplantation and a lighter-than-water, 5000 centistoke silicone oil endotamponade. The location of the donor site, the presence or absence of PVR development and the location of PVR were noted. The two-tailed Fisher’s exact test was used for statistical analysis. Results: Thirty-nine of 246 (15.9%) patients developed PVR, of whom 35 had a superior donor site and four an inferior donor site. Of the 209 patients without PVR, 155 had a superior donor site and 25 had an inferior one. For 27 patients, no donor site location was explicitly documented in the patient files. We found no difference between the groups with a superior or inferior donor site and the occurrence of PVR (p = 0.8). Conclusion: Shifting the inflammatory aqueous milieu away from the graft donor site does not prevent the occurrence of PVR. Transplantation of free grafts of retinal pigment epithelium (RPE) and choroid after removal of the submacular neovascular complex has previously been shown to be effective in patients with exudative age-related macular degeneration (AMD) not responding to less invasive treatment (Maaijwee & van Meurs 2007; Maaijwee et al. 2007; Van Zeeburg et al. 2012). However, this is a relatively traumatic vitreoretinal surgical procedure that requires a parafoveal retinotomy, a local submacular retinal detachment (RD) and a chorioretinotomy in the midperipheral retina. Retinal detachment due to proliferative vitreoretinopathy (PVR) is the most serious potential complication. Proliferative vitreoretinopathy is an inflammatory and fibrotic process that may complicate retinal tears, RD and vitreoretinal trauma. Following the breakdown of the blood-aqueous barrier, a pro-inflammatory and fibrotic milieu with macrophages, cytokines and growth factors develops in the hydrophilic compartment surrounding a posterior segment tamponade (Kirchhof & Sorgente 1989; Asaria et al. 2004). Retinal pigment epithelium cells, dispersed by the actual tearing of the retina, are believed to play a pro-fibrotic role in the development of PVR, and they are found in formed PVR membranes (Kirchhof & Sorgente 1989; Wu et al. 2000). Proliferative vitreoretinopathy has a predilection to occur in the inferior quadrants of the fundus. Gravity favours the deposition of dispersed RPE cells in these inferior quadrants, whereas the choice of tamponade [i.e. lighter or heavier (heavy silicone oil [HSO]) than water] determines whether the aqueous inflammatory milieu is compartmentalized superiorly or inferiorly in the posterior segment (Lambrou et al. 1987; Asaria et al. 2004; Heimann et al. 2008). The donor site of the RPE–choroid graft is chosen at either the 6 or 12 o’clock position in the midperiphery to avoid destruction of the vortex ampullae and the creation of a visually disturbing scotoma at the 3 and 9 o’clock positions. Superior donor retinotomies are closed by a lighter-than-water tamponade, with the hydrophilic pro-PVR milieu positioned inferiorly under the tamponade, whereas an inferior donor site is not covered by the tamponade but is instead in direct contact with the PVR milieu. Therefore, it was hypothesized that there might be a higher incidence of PVR in patients with an inferior donor site than in patients with a superior one. We analysed the occurrence of PVR in relation to the donor site location to test the hypothesis that shifting the pro-PVR milieu away from retinal tears or breaks might decrease the incidence of PVR, a concept that is central to the development of a heavier-than-water semi-permanent tamponade. Free RPE–choroid graft transplantations were performed from October 2001 through October 2011 in an institutional prospective cohort study at the Rotterdam Eye Hospital (REH). This study was approved by the Medical Ethical Committee (REH 2001-26 and MEC 2009-017), Rotterdam, the Netherlands. All patients provided informed consent for the procedure and examinations, in accordance with the tenets of the Declaration of Helsinki. The medical records of all the transplanted patients in this time frame were retrospectively reviewed. Inclusion criteria for this retrospective analysis of occurrence of PVR in this prospective cohort were exudative AMD, a posterior segment tamponade using 5000 centistoke (cSt) silicone oil and a perimacular retinotomy with a midperipheral donor site at the 6 or 12 o’clock position. Exclusion criteria were aetiologies other than exudative AMD, other tamponades, such as HSO or gas, or a 180° temporal retinectomy. We excluded all patients with a follow-up time shorter than 6 months, as most PVR cases develop in that time period (Mietz & Heimann 1995). We identified patients with PVR by notations in chart and reoperations for PVR. Proliferative vitreoretinopathy was defined as the presence of epiretinal tissue or shortening of the retina, leading to RD. Proliferative vitreoretinopathy could appear to originate from the donor site or the temporal retinotomy, or from another location entirely. The number and locations of the detached retina were noted. This surgical procedure has been described previously (Maaijwee & van Meurs 2007; Van Zeeburg et al. 2012). Briefly, the macular retina was separated from the RPE and/or submacular haemorrhage and/or choroidal neovascular membrane (CNV) by injecting a balanced salt solution into the subretinal space and thereby creating a local RD. A paramacular temporal retinotomy was made in the raphe, through which the CNV and, if present, the subretinal haemorrhage was extracted from the subretinal space. Residual blood or debris was removed by flushing the balanced salt solution under the macula. After significant diathermic coagulation or laser photocoagulation in the midperiphery at the 6 or 12 o’clock position, vitreous scissors were used to cut a full-thickness graft of retina, RPE, Bruch’s membrane and choroid (RPE–choroid graft). The graft was either loaded onto an aspiration-reflux spatula [Dutch Ophthalmic Research Centre (DORC), Zuidland, the Netherlands] (Maaijwee et al. 2008) or grasped from the choroidal side using fine forceps. The retina was removed from the graft, and the graft was repositioned underneath the macula through the existing paramacular retinotomy. Perfluorocarbon liquid was injected over the macula to hold the graft in position during retraction of the instrument. A vibration device attached to the forceps facilitated the release of the graft (Maaijwee et al. 2008). The midperipheral donor site was then encircled by laser photocoagulation. We left a silicone oil tamponade, after either fluid air or Perfluorocarbon air exchange. All eyes were completely filled with silicone oil; no distinction was made between eyes with superior or inferior donor sites. All surgical procedures were performed by one surgeon (JvM). The silicone oil was removed in a second procedure approximately 3 months after the first surgery in all patients. In phakic patients, lensectomy or phacoemulsification and insertion of an intraocular lens were performed during either the first or second procedure. In 291 patients, a free RPE–choroid graft transplantation was performed. In 24 patients, a 180° temporal retinectomy (flap-over technique) was used, in six a gas tamponade, and in four an HSO endotamponade. In two patients, the diagnosis was geographic atrophic AMD, and one patient had angiod streaks. Two patients were lost to follow-up because they lived abroad. Six patients had a follow-up shorter than 6 months. These patients were excluded from analysis. The data of the remaining cohort of 246 patients with an RPE–choroid graft were analysed retrospectively. These patients had a follow-up time ranging from 6 to 112 months, during which 39 patients were found to develop PVR (15.9%). Of the 246 patients, 219 donor site locations were known, including all 39 patients with PVR. These data are summarized in Table 1. Of the patients with a superior donor site, 18.4% (35/190) developed PVR, opposed to 13.8% (4/29) of the patients with an inferior donor site. Using the available data, no significant difference was found between the patients with a superior or inferior donor site and the development of PVR (p = 0.8, two-tailed Fisher’s exact test). If we would assume that all missing patients had inferior donor sites, we still find no significant difference between the two groups based on the assumed data; p = 0.06. If we would assume that all missing 27 donor sites had superior donor sites, we find p = 1. The donor site data of the 27 missing patients would thus not influence these results. Based on our data, we cannot find a statistically significant difference between the donor site location and the occurrence of PVR. The 39 patients with PVR had a mean age of 78.2 years (range 57–96). Median preoperative visual acuity was 1.0 logMAR (range 0.5–2.8), with one patient having only light perception (LP+). Median visual acuity at the last follow-up was 1.95 logMAR (range 0.78–2.8), with additionally two patients with LP+ and one patient with no light perception (LP−). Median follow-up time of the 39 PVR patients was 31 months (range 6–85 months). In 17 of the 39 patients, silicone oil tamponade was still present at last follow-up visit. Retinal detachment due to PVR developed in the 39 patients between 1 and 18 months after graft surgery, with a median of 4.5 months. Between one and four quadrants were involved, with a median of two quadrants. Twenty-four patients had a RD of the inferior quadrants, of whom 22 had a superior donor site and two an inferior donor site. Contraction was noted around the retinotomy in the raphe in two patients with a superior donor site. Three patients had a RD in the superior quadrants, all with a superior donor site. Two of them had contraction at the superior donor site. In five patients, the RD involved both the superior and inferior quadrants. Three had a superior donor site and two an inferior one. In one of them, contraction was noted at the superior donor site. One patient had a RD in the temporal quadrants originating from contraction at the retinotomy at the raphe whilst having a superior donor site. Three patients had a total RD; all three had a superior donor site. One of these patients showed contraction at the retinotomy in the raphe. In three patients, no information on a specific site of epiretinal contraction could be found. In summary, epiretinal contraction originated from either the donor site (n = 3) or the retinotomy in the raphe (n = 4) in seven patients. In all other patients, epiretinal tissue developed distant from the donor site. The information about the location of the RD and the donor site is summarized in Table 2. In the described technique of a free RPE–choroid graft translocation, the creation of two retinotomies (a superior or inferior donor site and a temporal paramacular retinotomy) and a local RD in the macula causes blood–retina barrier breakdown and may disperse RPE cells. Older haemorrhages and/or peroperative bleeding may further contribute to a pro-inflammatory and pro-fibrotic milieu favouring the development of PVR. The frequent development of PVR is a major concern of this elective surgical technique (Joussen et al. 2006; MacLaren et al. 2007; Heussen et al. 2008; Van Zeeburg et al. 2012). In this study, in order to try and find ways to decrease the incidence of PVR, we address whether there was a correlation between the incidence of PVR and the location of the donor site. With the use of lighter-than-water silicone oil, a higher incidence of PVR would be expected in patients with an inferior donor site, as the hydrophilic milieu is located inferiorly, in direct contact with the donor retinotomy. However, the apparent origin of epiretinal contraction was located near either the donor site or the paramacular temporal retinotomy in <20% of the patients. Furthermore, no correlation between the donor site location and occurrence of PVR was found. Thus, the expected higher incidence of PVR in patients with a donor site retinotomy at 6 o’clock was not apparent. The findings of the current study are similar to the failure to demonstrate superiority of a heavy tamponade in the treatment for inferior PVR in the HSO study (Joussen et al. 2011). Both observations show that neither direct closure of retinal breaks by the endotamponade nor compartmentalizing of the aqueous milieu away from the retinal breaks prevents PVR. The aqueous milieu appears to contain sufficient cells and agents to produce PVR, regardless of the presence of a closed or open break. Additionally, in preventing fluid movement through a retinal break, actual closure by direct contact with the tamponade may not be necessary; restriction of the fluid phase, as under a lighter-than-water tamponade such as gas or silicone oil, may sufficiently reduce fluid movements (Angunawela et al. 2011). Therefore, the challenge would be to find ways of modulating the inflammatory aqueous milieu. Shifting the aqueous phase does determine the site of PVR, however (Joussen et al. 2009). In the current study, PVR manifested itself primarily in the inferior quadrants, where gravity may slow the progression of RD. In the HSO study, however, PVR developed in the superior quadrants, which is clinically less desirable as the resulting RD tends to be more rapidly progressive. A drawback of the current study is the lack of sufficient consistent information concerning the preoperative situation of each patient. If extensive macular haemorrhage was present before surgery, the graft was more likely to be taken superiorly, as the inferior retina would be more likely to have been damaged by the haemorrhage. Furthermore, existence of haemorrhage before surgery might have increased the chance of the development of PVR. Thus, patients with an inferior donor site may represent a subgroup of patients with fewer risk factors for PVR. Nevertheless, this study’s findings establish that surgeons may choose the donor site where the RPE appears least damaged, as the results do not support the hypothesis that shifting the hydrophilic pro-inflammatory and fibrotic milieu away from retinal breaks might prevent the occurrence of PVR. This study has been funded/supported by The Rotterdam Eye Hospital Flieringa Research Foundation, Rotterdam, the Netherlands, and Royal Visio, Rotterdam, the Netherlands. We would like to thank L. Spielberg for manuscript editing. J.C. van Meurs is the partial owner of a patent: vibration device for tissue release, with Dutch Ophthalmic Research Centre (DORC), Zuidland, the Netherlands, one prototype. The other authors have no financial disclosure. An abstract of this article was presented at the 6th St. Christoph Vitrectomy Meeting, Kleine Scheidegg, Wengen, Switzerland. 15–17 January 2012." @default.
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• W2051237447 title "There is no relation between the occurrence of proliferative vitreoretinopathy and the location of the donor site after transplantation of a free autologous retinal pigment epithelium-choroid graft" @default.
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