Visual acuity of 20/32, 13.5 years after a retinal pigment epithelium and choroid graft transplantation.

PURPOSE: To present the 13.5-year-survival of an autologous retinal pigment epithelium (RPE) and choroid graft transplantation with good visual acuity results. OBSERVATIONS: A 72-year old patient presented with a 5-weeks-old visual acuity deterioration to excentric finger counting at half a meter. Fundoscopy showed a fibrotic macular scar, a large subretinal hemorrhage, partly recent, combined with intraretinal fluid, blood, and hard exudates. RPE-choroid graft surgery was performed, and visual acuity improved to 20/32, and maintained up until 13.5 years postoperative. Microperimetry performed at the same time revealed a 3.4 dB sensitivity, with fixation on the graft. During the postoperative years glaucoma developed, an uveitis anterior was treated, and to treat a small Coats' like lesion; one bevacizumab injection was administered. CONCLUSIONS AND IMPORTANCE: A best corrected visual acuity of 20/32 could be achieved and maintained up to 13.5 years after an RPE-choroid graft transplantation, despite an unfavorable preoperative presentation and some early and late complications. This case is a proof of principle that an RPE-choroid graft harvested from the midperiphery can support the macular metabolism up to 13.5 after surgery in a patient with severe exudative AMD. It also represents a rationale for pursuing stem cell derived RPE replacement. Anti-vascular endothelial growth factor injections are nowadays the mainstay of therapy for choroidal neovascularization and/or small hemorrhages and offer good results. Nevertheless, selected patients that cannot benefit from this therapy may profit from an autologous RPE-choroid graft transplantation.

Deferred laser photocoagulation of relaxing retinotomies under silicone oil tamponade to reduce recurrent macular detachment in severe proliferative vitreoretinopathy.

PURPOSE: This study sought to investigate whether, in patients with retinal detachment complicated by proliferative vitreoretinopathy, we can re-attach the retina with a posterior relaxing retinotomy and silicone oil tamponade while postponing laser retinopexy for several months. METHODS: In 13 consecutive patients we applied laser coagulation of the retinotomy edge 15 ± 12 weeks after surgery. Silicone oil was removed 9 ± 6 weeks after laser application. RESULTS: After the retinotomy without laser, some degree of central shifting was seen in all patients, followed by obvious curling in 10 patients. The total follow-up was 24 ± 7 months after retinotomy and 13 ± 9 months after oil removal. The retina was attached in 12 patients at the last visit, with the oil still in situ in three patients. Seven patients, however, required additional surgery. Function remained stable with a mean preoperative and postoperative Snellen visual acuity of 0.09. CONCLUSIONS: Not anchoring retinotomy edges with a laser at the time of surgery allows inward curling and central slippage of retinal edges under silicone oil. This appears to compensate for the retinal fibrosis occurring in the weeks following surgery and may result in less macula-off re-detachments under oil, and potentially, in better visual outcome.

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.

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.

A free retinal pigment epithelium-choroid graft in patients with exudative age-related macular degeneration: results up to 7 years.

PURPOSE: To report and analyze long-term best-corrected visual acuity (BCVA) outcomes following a free autologous retinal pigment epithelium (RPE)-choroid graft translocation in patients with exudative age-related macular degeneration (AMD). DESIGN: Prospective cohort study. SETTING: Institutional. STUDY POPULATION: One hundred and thirty consecutive patients (133 eyes) with AMD underwent RPE-choroid graft translocation between October 2001 and February 2006. All patients had a subfoveal choroidal neovascular membrane with or without hemorrhage and/or an RPE tear. All were either ineligible for or nonresponsive to photodynamic therapy, the standard treatment at the time of surgery. OBSERVATION PROCEDURES: Data collection included preoperative and postoperative visual acuity measurements, fundus photography, fluorescein and indocyanine green angiography, and microperimetry. MAIN OUTCOME MEASURES: Postoperative BCVA. RESULTS: The mean preoperative BCVA was 20/250. Four years after surgery, 15% of the eyes had a BCVA of >20/200, and 5% had a BCVA of ≥20/40. One patient achieved a BCVA of 20/32, which was maintained at 7 years after surgery. Complications consisted of proliferative vitreoretinopathy (n = 13), recurrent neovascularization (n = 13), and hypotony (n = 2). CONCLUSIONS: RPE-choroid graft transplantation may maintain macular function for up to 7 years after surgery, with relatively low complication and recurrence rates. Retinal sensitivity, BCVA data, and fixation on the graft suggest that the graft, rather than simply the removal of submacular hemorrhage and/or choroidal neovascular membrane, was responsible for the preservation of macular function. This surgery may be an alternative for patients with AMD who cannot undergo other standard treatment.

Single-sided and small-scaled grasping of delicate tissues: effectiveness of indirect heat-induced attachment and detachment.

INTRODUCTION: Indirect heat-induced attachment and detachment (iHIAD) is a promising concept for gripping delicate tissues in microsurgery. However, the optimal settings of iHIAD are unknown. This study evaluates the effects of the instrument heating properties and initial contact force on the adhesion force, detachment success and thermal damage. MATERIAL AND METHODS: An instrument prototype was developed to test attachment and detachment for different combinations of generated energy (3.5-20.0 mJ) and pulse length (0.25-2.50 ms). The tissues tested on were kidney and eye from the pig. Thermal tissue damage was estimated with a histological analysis. RESULTS: The adhesion force F(a) depended strongly on the amount of generated energy (F(a) = 0.03-2.5 mN) and contact force (F(a) = 0.25-1.0 mN). Pulse length played a minor role. Detachment success (0-100%) was determined by generated energy (3-16 mJ). Histological analysis showed minimal damage. CONCLUSION: Adhesion forces increased with increasing contact forces. iHIAD proved sensitive to heating characteristics. Detachment success increased with generated energy. Thermal damage was minimal. iHIAD creates a potential to build better performing tissue manipulators.

Reliability testing of the Dutch version of the Radner Reading Charts.

PURPOSE: To statistically analyze the test-retest and inter-chart reliability of the newly developed actual logarithmically scaled Dutch Radner Reading Charts in an older population affected by macular disease. These Dutch Radner Reading Charts are developed according to the strict principles of sentence construction of the originally German language Radner Reading Charts. METHODS: Thirty-six subjects aged 50 years or older and affected with a macular disease monocularly read the three charts of the Radner Reading Charts in a randomized order twice with 1 month in between. The subjects were divided into three groups according to their distance logMAR visual acuity (group 1, > or =0.1; group 2, 0.12 to 0.4; and group 3, 0.42 to 0.8). Reading acuity (logRAD, the reading equivalent of logMAR), logRAD score, maximum reading speed, critical print size, and logRAD/logMAR ratio were measured. Variance component analysis was used to determine the sources of variability. RESULTS: The test-retest and inter-chart reliability was high for all visual acuity groups and variables. For all groups together the chart accounted for maximal 5% of the total variability for all measurements. The individual subject did have the largest influence on the measurements (88 to 98% of the variability). CONCLUSIONS: The Dutch version of the Radner Reading Charts provided high reliable test-retest and inter-chart measurements of reading performance in a heterogeneous group of subjects with subnormal to low vision. This study also showed that the strict principles of sentence construction of the originally German Radner Reading Charts may also be successfully used for other languages.

Threshold amplitude and frequency for ocular tissue release from a vibrating instrument: an experimental study.

PURPOSE: During retinal pigment epithelium (RPE) and choroid graft translocation in the treatment of patients with exudative age-related macular degeneration, the adhesion of the graft to the translocation instrument complicated its submacular release. Vibration of the instrument improved the release of the graft. This study was conducted to validate the effectiveness of the principle of vibration and to determine the threshold amplitude and frequency required for development of an optimized instrument. METHODS: An experimental in vitro model with fresh porcine RPE-choroid grafts was used. Release of the graft was studied by a masked observer for amplitudes in the range of 0.05 to 1.2 mm and frequencies in the range of 25 to 200 Hz in the horizontal plane. RESULTS: The minimum threshold amplitude required to release the graft was approximately 0.15 mm from a frequency of 100 Hz and higher. CONCLUSIONS: This study confirmed the clinical experience that vibration of an instrument induces the release of the RPE-choroid graft. The minimum threshold amplitude and frequency needed for optimum tissue release were estimated.

Angiographic evidence for revascularization of an rpe-choroid graft in patients with age-related macular degeneration.

PURPOSE: To study graft perfusion using fluorescein angiography (FA) and indocyanine green angiography (ICG) after the translocation of an autologous retinal pigment epithelium (RPE)-choroid graft in patients with exudative age-related macular degeneration (AMD). METHODS: Retrospective observational case series of 31 patients with AMD who had FA and/or ICG performed after an RPE-choroid graft translocation. The FAs (n = 25) and ICGs (n = 23) were assessed by an independent masked reader for the presence of early fluorescence of the graft in FA, and for perfusion of the choroidal vessels of the graft and recipient bed in ICG. RESULTS: Early fluorescence of the graft was present in 23 of the 25 FAs. Perfusion of the graft vasculature was observed in 12 of the 23 ICGs. The two grafts that lacked early fluorescence in FA also had no signs of choroidal perfusion of the graft and the recipient bed with ICG. CONCLUSION: Revascularization of the RPE-choroid graft was observed in all but 2 of the 31 patients either by early fluorescence of the graft by FA or by identification of perfused choroidal graft vessels with ICG from 1 week up to 3 years after surgery. For assessment of revascularization of the graft evaluation of the early phase of the FA is recommended.

Influence of intraoperative course on visual outcome after an RPE-choroid translocation.

PURPOSE: In a previous study, preoperative variables were correlated with postoperative visual outcome after the translocation of a free RPE-choroid graft. The present study was conducted to investigate whether the intraoperative course was an independent factor influencing visual outcome in these patients. METHODS: This was a prospective interventional case series of 48 patients with exudative AMD treated with an RPE-choroid translocation. Preoperative and postoperative evaluation included ETDRS visual acuity (VA) and fixation testing by a masked examiner. Four critical surgical steps were evaluated, and the intraoperative course was graded from 0 (uncomplicated surgery) to 5 (most complicated surgery). The relationship between intraoperative course adjusted for preoperative delay/lesion composition and visual outcome at 3 months and 1 year after surgery was analyzed with multivariate analysis. RESULTS: The mean VA (logMAR) improved slightly from 0.99 before surgery to 1.00, 0.94, 0.89, and 0.91 after 3, 6, 9, and 12 months, respectively. Foveal fixation on the graft was present in 34 (71%) of the eyes at 1 year after surgery. The intraoperative course was statistically significantly associated with the DeltaVA (logMAR) at 3 months (P = 0.037) and at 1 year after surgery (P = 0.020) and if measured as gain or loss of > or =2 ETDRS-lines (odds ratio [OR] 1.8, 95% confidence interval [CI] 1.7 to 2.8, P = 0.027) and > or =3 ETDRS lines (OR, 2.2, 95% CI 1.9-3.5, P = 0.003); better surgery was associated with visual gain whereas eventful surgery was associated with visual loss. CONCLUSIONS: The intraoperative course adjusted for preoperative variables had a statistically significant influence on postoperative visual outcomes in patients treated with a free RPE-choroid translocation. Refining the surgery could improve results.

Retinal pigment epithelium and choroid translocation in patients with exudative age-related macular degeneration: long-term results.

BACKGROUND: To study the results of the translocation of a free autologous retinal pigment epithelium (RPE)-choroid graft after removal of a subfoveal choroidal neovascular membrane in patients with exudative age-related macular degeneration (AMD), and to determine whether preoperative variables may predict visual outcome at 1 year after surgery. METHODS: Prospective interventional case series of 84 eyes of 83 consecutive eligible patients with exudative AMD with a minimal follow-up of 1 year after surgery. Of this group, 45, 24 and 11 patients reached a follow-up of respectively 2, 3 and 4 years. Pre- and postoperative evaluation included ETDRS visual acuity (VA), fixation testing and color fundus photography. Preoperative fluorescein angiograms were assessed by masked readers for lesion size, size of hemorrhage and lesion composition according to the MPS criteria. The relationship between lesion composition adjusted for preoperative delay and VA, lesion size, percentage of blood, and visual outcome at 1 year after surgery was analyzed. RESULTS: The mean VA (logMAR) improved slightly at 1 and 2 years (0.89, Delta = -0.06), 3 years (0.79, Delta = -0.16) and 4 years (0.74, Delta = -0.21) after surgery. Five patients had a preoperative VA better than 20/80, compared to 19 out of 84, six out of 45, four out of 24 and two out of 11 after 1, 2, 3 and 4 years respectively. Fixation was located on the graft in 62 patients (74%) up to the last examination. Predominantly classic and occult lesions had a significant better prognosis than minimally classic or hemorrhagic (> or = 50% blood) lesions. Retinal detachment occurred in seven patients; two caused by rhegmatogenous detachment and five caused by proliferative vitreoretinopathy. In 11 eyes, a recurrent or persisting neovascular membrane was observed. CONCLUSION: An autologous free RPE-choroid graft may stabilize or improve vision in patients with exudative AMD up to 4 years after surgery.

In vivo retinal tolerance of various heavy silicone oils.

PURPOSE: Heavy silicone oils are currently under investigation as a permanent tamponade in eyes with inferior PVR. This study was an investigation of Densiron 68 (Fluoron GmbH, Neu-Ulm, Germany) and several new heavy silicone oil admixtures on the basis of the perfluoroalkanes F4H5 (perfluorobutylpentane), F4H6 (perfluorobutylhexane), and F4H8 (perfluorobutyloctane) with respect to their long-term tolerance in a rabbit model. METHODS: Because of the better solubility of the F4Hn-species (n = 5-8) in comparison to F6H8, we used F4H5, F4H6, and F4H8 to generate highly viscous, heavy silicone oils (HSO). After vitrectomy and fluid-air exchange, the left eye of each of five rabbits per group was filled with HSO 68-1500 (Densiron 68), HSO 45-5000, HSO 45-3000, HSO 46-5000, HSO 46-3000, HSO 48-5000, or HSO 48-3000, or pure F4H5, F4H6, or F4H8. Detailed clinical investigation, ERG testing, and histologic evaluation were performed throughout a 3-month follow-up. RESULTS: Densiron 68 and HSOs based on F4H5, as well as the three control oils (silicone oil of 1000, 3000, and 5000 mPa . s) were well tolerated over 3 months. Histologically, the retina was unaffected. In contrast, intraocular inflammation, cataract formation, and retinal detachment and degeneration were noticed in all groups with HSOs based on F4H6 or F4H8. CONCLUSIONS: Biocompatibility of the new HSOs is dependent on the lipophilic behavior (R(F)/R(H) ratio) and furthermore on the molecular dimension of the used semifluorinated alkanes (SFAs). HSOs on the basis of F4H5 may have advantages over silicone oils, on the basis of F6H8, for use as a tamponade agent for the inferior retina in difficult retinal situations.

Histological evidence for revascularisation of an autologous retinal pigment epithelium--choroid graft in the pig.

BACKGROUND: Translocation of a free autologous graft consisting of retinal pigment epithelium (RPE), Bruch's membrane, choriocapillaris and choroid in patients with exudative age-related macular degeneration is currently being evaluated in clinical practice. Angiographic studies in these patients suggest that their grafts become revascularised. AIM: To investigate the histological evidence of revascularisation of the graft in a porcine model. METHODS: In 11 pigs (11 eyes), an RPE-choroid graft was translocated from the mid-periphery to an intact or an intentionally damaged RPE and Bruch's membrane at the recipient site. The eyes were enucleated 1 week or 3 months after surgery. Tissue sections were evaluated using immunohistochemistry. RESULTS: Bridging vessels between recipient layer and graft were identified from 1 week to 3 months after surgery. This reconnection occurred regardless of whether the Bruch's membrane of the recipient site was left intact or intentionally damaged at the time of transplantation. The vasculature of the graft appeared open and perfused. Vessels with transcapillary pillars and conglomerates of small new vessels were present in the graft. CONCLUSIONS: This study showed histological evidence for revascularisation by angiogenesis of a free autologous RPE-choroid graft.

Effect of gravity in long-term vitreous tamponade: in vivo investigation using perfluorocarbon liquids and semi-fluorinated alkanes.

PURPOSE: In order to investigate whether gravity is the reason for retinal degeneration in long-term vitreous tamponade, perfluorohexyloctane (F6H8), perfluorodecalin (PFD), and a mixture of F6H8/PFD were compared. MATERIALS AND METHODS: Each group of 5 rabbits received a 3-month tamponade with either PFD (pure) (1.93 g/cm(3)), F6H8 (pure) (1.33 g/cm(3)), or a 1:1 mixture of F6H8/PFD (1.62 g/cm(3)). Electroretinograms (ERG) were performed pre- and postoperatively. Lower and upper retinal areas were compared using immunohistochemical methods. Transmission electron microscopy was performed to investigate alterations in the photoreceptors. RESULTS: All three substances were tolerated well in rabbit eyes for up to 3 months. Dispersion was seen earliest with PFD and latest with pure F6H8. None of the substances demonstrated inflammatory reactions or vascular alterations. ERGs were not considerably altered with any of the substances. Histology of the retina showed alterations in the cell counts within the inner and outer nuclear layer that were not attributable to the gravity of the tamponading agent. CONCLUSION: In contrast to previously published work, this study did not detect any tamponade-related structural damage of the retina after a 3-months tamponade in the rabbit model. Based upon this study, we conclude that gravity might not be causally linked to retinal damage.

Autologous translocation of the choroid and retinal pigment epithelium in age-related macular degeneration.

PURPOSE: To evaluate the autologous translocation of peripheral choroid and retinal pigment epithelium (RPE) in 45 eyes of 43 patients with age-related macular degeneration (AMD). DESIGN: Prospective nonrandomized study. METHODS: All patients had visual loss due to AMD (n = 5 classic membranes, n = 14 occult, n = 2 mixed, n = 16 pigment epithelial detachment (PED), n = 5 subretinal hemorrhage, n = 3 geographic atrophy). After extraction of the neovascular complex, an autologous peripheral full-thickness explant of RPE, Bruch membrane, and choroid was translocated from the midperiphery to the macula. RESULTS: Preoperative distant visual acuity ranged from 20/800 to 20/40. Reading vision ranged from 1.4 logarithm of reading acuity determination (logRAD) to 0.5 logRAD (0.04 to 0.32 Snellen equivalent). Revision surgery was required in 22 eyes as a result of proliferative vitreoretinopathy (PVR), retinal detachment, macular pucker, or vitreous hemorrhage. In eight patients, the patch was renewed. At six months, distant visual acuity ranged from light perception to 20/50 (increase of 15 letters in four eyes). Reading vision ranged from 1.4 to 0.4 logRAD. Visual outcome was unrelated to the type of AMD. Vascularization of the transplant was visible on indocyanine green (ICG) angiography in 40 of 42 eyes. In most patients, autofluorescence of the pigment epithelium was coincident with revascularization of the graft. Fixation on the patch was positively related to visual acuity. CONCLUSIONS: Autologous translocation of a full-thickness transplant of choroid and RPE usually results in a vascularized and functioning graft. Vascularization was even achieved in patients with geographic atrophy. Fixation stability and microperimetry before the patch translocation may be helpful in selecting patients who will profit from surgery.

Especially polymorphonuclear leukocytes, but also monomorphonuclear leukocytes, roll spontaneously in venules of intact rat skin: involvement of E-selectin.

White blood cells roll spontaneously in venules of intact, noninflamed rat skin. We investigated noninvasively in two experimental series which leukocyte subtypes participate in this phenomenon and the possible involvement of E-selectin. Male Lewis rats were anesthetized with sodium pentobarbital, and intravital video microscopy was performed on postcapillary venules in the nail-fold of a hind leg. In series 1 acridine yellow was infused for 15 min (50 mg per kg intravenously) to stain the leukocyte nuclei in situ. With the use of fluorescence microscopy rolling leukocytes could be classified unequivocally as polymorphonuclear (granulocytes) or monomorphonuclear (lymphocytes/monocytes) by the shape of their nucleus. Irrespective of vessel depth beneath the skin surface (25-45 microm), most identified rolling leukocytes were classified as granulocytes (72%-100%; median 89%). This percentage was independent of total rolling leukocyte flux, systemic leukocyte count, or their in vitro differentiation pattern. In series 2, rats were treated with either a synthetic, highly selective E-selectin blocking peptide or a control peptide (intravenously, 12 mg peptide per kg bolus, followed by 50 mg per kg per h). E-selectin blockade significantly reduced the leukocyte rolling level to about 50% of baseline (p <0.01), whereas the rolling velocity increased (p <0.01); the control peptide had no effect. In summary, most of the leukocytes rolling spontaneously in postcapillary venules of intact rat skin are granulocytes, despite the absence of an acute inflammatory reaction. One of the adhesion molecules involved in this phenomenon is E-selectin.