Felix Treumer

Pars plana vitrectomy, phacoemulsification and intraocular lens implantation. Comparison of clinical complications in a combined versus two-step surgical approach.

PurposeTo report intra-and postoperative complications in pars plana vitrectomy, phacoemulsification and intraocular lens implantation. A comparison of the combined versus two step surgical approach is given.MethodMedical records and operative notes of 111 eyes with combined surgery and 50 eyes with sequential surgery were retrospectively analysed. Subgroup analysis was performed to evaluate differences in disease groups, the use of endotamponading or endolaser and cryocoagulation. Postoperative follow-up time was between 3 and 18 months.ResultsCombined surgery: 64 eyes (57.5%) showed no complications. 17 eyes (15.3%) showed transient intraocular pressure rise, 17 eyes (15.3%) fibrinous exudation in the anterior chamber. Posterior capsule tears occurred in 7 eyes (6,3%), formation of posterior synechia was observed in 7 eyes (6.3%). IOL dislocation was seen in 3 eyes (2.7%), heavy covering of macrophages in 3 eyes (2,7%). Rare complications included silicon oil efflux into the anterior chamber (1.8%), anterior chamber hemorrhage (1,8%) and iris incarceration into the corneoscleral incision (0,9%). One eye needed explantation of the IOL during the follow-up. Sequential surgery: 31 eyes (62%) showed no complication. Transient intraocular pressure rise occurred in 14 eyes (28%), fibrinous exudation in 2 eyes (4%). Formation of posterior synechia was observed in 1 eye (2%), posterior capsule tears occurred in 4 eyes (8%). Dislocation of the IOL was seen in 1 eye (2%). Subgroup analysis revealed fibrinous exudation in the anterior chamber to be significantly more frequent after combined surgery, particularly in cases of proliferative diabetic retinopathy.ConclusionCombined pars plana vitrectomy, phacoemulsification and intraocular lens implantation as well as the two-step procedure are safe and effective. Sequential surgery could be advantageous to minimize the postoperative anterior chamber inflammatory response.

Autologous retinal pigment epithelium–choroid sheet transplantation in age related macular degeneration: morphological and functional results

Objective: To evaluate the outcome of autologous retinal pigment epithelium (RPE)–choroid sheet transplantation after removal of a subfoveal choroidal neovascularisation (CNV) in patients with age related macular degeneration (AMD). Methods: RPE–choroid sheet transplantation was performed in 10 consecutive patients with exudative AMD (n = 9) or geographic atrophy (n = 1). After CNV extraction, an autologous RPE–choroid patch was translocated from the midperiphery under the macula. Follow-up was between 6 and 12 months. Visual acuity testing and microperimetry (Nidek-MP1) as well as autofluorescence, fluorescein and indocyanine green (ICG) angiography were performed and the data were analysed retrospectively. Results: Visual acuity (logarithm of minimum angel of resolution) before operation ranged from 0.7 to 1.8 (mean 1.37) and after operation from 0.4 to 1.6 (mean 1.24). Visual acuity after operation improved in seven patients (by a mean of 0.26), remained stable in one patient and decreased in two patients. Microperimetry showed light sensitivity and fixation on the sheet in five cases. ICG angiography demonstrated perfusion through the RPE–choroid graft in nine patients. Postoperative complications included retinal detachment (n = 1) and epiretinal membrane formation (n = 2). The patient with geographic atrophy developed a CNV after surgery. Conclusions: Autologous RPE–choroid sheet transplantation is feasible and a comparatively safe procedure. Microperimetry showed fixation and light perception over the graft with a moderate increase in mean visual acuity.

Subretinal coapplication of recombinant tissue plasminogen activator and bevacizumab for neovascular age-related macular degeneration with submacular haemorrhage

Aim: To evaluate the efficacy and safety of pars plana vitrectomy (ppV) with subretinal coapplication of recombinant tissue plasminogen activator (rtPA) and bevacizumab, and fluid–gas exchange for neovascular age-related macular degeneration (AMD) with submacular haemorrhage (SMH). Methods: Consecutive interventional case series of 12 patients with neovascular AMD with SMH with a maximum history of 14 days. All patients underwent ppV with subretinal coapplication of rtPA and bevacizumab, and fluid–gas (20% SF6) exchange. Phakic patients underwent concomitant cataract surgery. Additional injections of bevacizumab were applied intravitreally 4 and 8 weeks postop. Results: Complete displacement of SMH from the fovea was achieved in 9 of 12 patients. The mean best-corrected visual acuity (BCVA) improved significantly from preop logMAR 1.9 (range 3.0 to 0.7) to logMAR 1.2 (range 3.0 to 0.3) at 4 weeks postop (p = 0.01) and to logMAR 0.9 (range 1.6 to 0.2) at 12 weeks postop (p = 0.006). The mean improvement of BCVA 4 weeks postop as compared with preop was logMAR 0.7 (range −0.2 to 2.3). The mean improvement of BCVA 12 weeks postop as compared with preop was logMAR 0.96 (range −0.3 to 2.8). Overall, at 12 weeks postop, BCVA had improved in 10 patients, remained unchanged in one patient and worsened in one patient. Conclusion: PpV with subretinal coapplication of rtPA and bevacizumab, and fluid–gas exchange effectively displaces SMH and improves visual acuity in most patients.

Long-term outcome of subretinal coapplication of rtPA and bevacizumab followed by repeated intravitreal anti-VEGF injections for neovascular AMD with submacular haemorrhage

Aim To evaluate short-term and long-term outcomes of subretinal coapplication of recombinant tissue plasminogen activator (rtPA) and bevacizumab followed by intravitreal injections of bevacizumab or ranibizumab for neovascular age-related macular degeneration with submacular haemorrhage (SMH). Methods Retrospective, consecutive, interventional case series of 41 eyes of 40 patients. All patients underwent pars plana vitrectomy with subretinal coapplication of rtPA and bevacizumab and intravitreal gas tamponade. Postoperatively, repeated intravitreal injections of bevacizumab or ranibizumab were applied following a flexible, predominantly visual acuity-driven re-treatment regimen. Results Mean diameter of SMH was 4.5 disc diameters (range 1.5–12). Complete displacement of SMH was achieved in 35 of 41 eyes. Large and prominent SMH extending beyond the vascular arcades were completely displaced in six of eight eyes. SMH recurred in eight eyes after a mean of 9.1 months (2–19). A mean of 4.5 (2–9) intravitreal anti-vascular endothelial growth factor injections were applied during 12 months postoperatively. Short-term (3 months, n=41), mean best corrected logMAR visual acuity (BCVA) improved significantly from the preoperative value 1.7 (3.0–0.5) to 0.8 (1.6–0.2). 12 eyes had reading ability (≤logMAR 0.4) and 29 eyes had gained ambulatory visual acuity (≤logMAR 1.6). Long-term (mean 17 months (12–32), n=26) BCVA was 0.9 (1.6–0.1). Compared with short-term, BCVA had decreased in 12 of 26 eyes. Conclusion The operation effectively displaces small and large SMHs. In the long-term, a predominantly visual acuity-driven re-treatment regimen puts the initial functional improvement at risk. More sensitive re-treatment parameters may help to improve long-term functional outcome.

Foveal Structure and Thickness of Retinal Layers Long-Term after Surgical Peeling of Idiopathic Epiretinal Membrane

PURPOSE To better understand the long-term effect of idiopathic epiretinal membrane peeling on retinal anatomy, the foveal structure and the thickness of individual retinal layers were analyzed with frequency-domain optical coherence tomography (fdOCT). The long-term postoperative course of macular thickness was followed. METHODS fdOCT scans were obtained from the horizontal midline in 33 eyes long-term (mean 46 ± 13 months) after surgery and in 30 eyes of age-matched controls. Raw images were exported, and the thickness of retinal layers was measured with a manual segmentation procedure aided by a customized computer program. Macular thickness was quantified over time with the time-domain (td) OCT Fast Macular Thickness program. RESULTS Thickness of retinal layers between the outer nuclear and the ganglion cell plus inner plexiform layers in the horizontal midline of the fovea and the nasal parafovea was greater than normal, whereas that of the RPE, photoreceptor, and retinal nerve fiber layers was not different from controls. Twelve of 33 eyes had a foveal pit though the median foveal shape was distorted. Central macular thickness quantified with tdOCT remained increased, whereas the decrease of nasal macular thickness toward normal values was incomplete and delayed to 35 months after surgery. Superior, temporal, and inferior macular thickness returned to normal 12 to 14 months after surgery. CONCLUSIONS Long-term after surgery, the fovea and the nasal parafovea remain thickened between the outer nuclear layer and the ganglion cell layer, whereas the superior, temporal, and inferior macular thickness returns to normal. Long-term observations are required in the assessment of macular recovery from mechanical stress.

Vectorial release of matrix metalloproteinases (MMPs) from porcine RPE-choroid explants following selective retina therapy (SRT): towards slowing the macular ageing process.

The purpose of this study was to investigate release of matrix metalloproteinases (MMP) 2 and 9 during retinal pigment epithelium (RPE) wound healing after Selective Retina Therapy (SRT) with laser energy levels below and above the threshold of RPE cell death. Following exposure to SRT using a prototype pulsed Nd:YLF laser with energies of 80-180 mJ/cm(2) fresh porcine RPE-monolayers with Bruchs membrane and choroid were cultured in modified Ussing chambers which separate the apical (RPE-facing) and basal (choroid facing) sides of the RPE monolayer. Threshold energy for RPE cell death and wound healing were determined with calcein-AM viability test. Inactive and active forms of MMP 2 and 9 were quantified within tissue samples and in the culture medium of the apical and basal compartments of the Ussing chamber using gelatine zymography. Laser energies of 160-180 mJ/cm(2) resulted in cell death within 1 h while 120-140 mJ/cm(2) resulted in delayed death of exposed RPE cells. All cells survived 80 and 100 mJ/cm(2). Laser spots healed within 6 days after SRT accompanied by a transient vectorial increase of MMPs. SRT with 180 mJ/cm(2) increased active MMP 2 by 1.9 (p < 0.05) and 1.6 (p < 0.05) fold in tissue and basal compartments, respectively, without alterations in the apical compartment. Pro-MMP 2 levels were also significantly increased in all compartments (p < 0.05). Release of MMP 9 was not altered. Laser energy below the threshold of RPE cell death did not alter the release of MMP 2 or 9. The findings suggest that the release of active MMP 2 on the basal side of the RPE during wound healing following SRT may address age-related pathological changes of Bruchs membrane with a potential to slow degenerative macular ageing processes before irreversible functional loss has occurred.

Safety testing of indocyanine green with different surgical light sources and the protective effect of optical filters.

Purpose: The purpose of this study was to assess the light-induced cytotoxicity of indocyanine green (ICG) using different light sources commonly used in macular surgery and to assess the effect of optical filters. Methods: Primary cultures of porcine retinal pigment epithelium cells were incubated with 0.5 mg/mL ICG solution dissolved in 5% glucose and illuminated with a surgical light fiber for 3 or 15 minutes. Halogen, mercury vapor, xenon, and metal halide light sources were used. Cell viability was assessed using the MTT assay. Retinal pigment epithelium cells without illumination served as controls. The decomposition of ICG after illumination was analyzed by high-performance liquid chromatography. Results: Illumination of retinal pigment epithelium cells with all light sources with or without previous incubation with ICG did not affect cell viability compared with controls. Cell viability was significantly reduced when the cells were not rinsed immediately after incubation. The cytotoxic effect was abolished by a 475-nm long-pass filter. The high-performance liquid chromatography analysis of the illuminated ICG solution identified six cytotoxic ICG decomposition products. Conclusion: Optical filters that narrow the emission spectrum of the light sources reduce the light-induced cytotoxicity of ICG. Optical filters applied in ICG-assisted macular surgery may reduce the risk of intraoperative cell damage.

The Long-Term Course of Functional and Anatomical Recovery After Macular Hole Surgery

PURPOSE To investigate the long-term effect of macular hole surgery, foveal structure and the thickness of retinal layers were analyzed with spectral-domain optical coherence tomography (SD-OCT). The long-term postoperative course of macular thickness and best-corrected visual acuity (BCVA) were followed. METHODS In a retrospective cohort study, SD-OCT scans were obtained from the horizontal midline in 51 eyes 54±20 months postoperatively and from 30 control eyes. Retinal layer thickness was measured with a manual segmentation procedure aided by a customized computer program. BCVA was followed and macular thickness was quantified over time with the time-domain (TD) OCT Fast Macular Thickness program for up to 91 months. RESULTS Median foveal thickness between the outer plexiform and ganglion cell layers was greater than normal while that of the other retinal layers was normal. The median foveal shape remained slightly distorted. The postoperative decrease of central macular thickness toward normal values was delayed to 28 months postoperatively. Nasal macular thickness was decreased to normal at 6 months while superior, temporal, and inferior macular thickness was decreased to normal at 1 to 2 months postoperatively. Preoperative mean BCVA was 20/100±3 lines. Postoperatively, mean BCVA was 20/44±2 lines at 3 to 6 months, 20/40±2 lines at 1 year, 20/32±2 lines at 2 years, and 20/28±1 line after a mean follow-up period of 54±20 months. CONCLUSIONS Long-term postoperatively, the median thickness of retinal layers remains slightly thickened between the outer plexiform and the ganglion cell layer. The process of gradual recovery may continue for several years after macular hole surgery.

Compatibility of recombinant tissue plasminogen activator and bevacizumab co-applied for neovascular age-related macular degeneration with submacular hemorrhage.

OBJECTIVE To investigate the compatibility of recombinant tissue plasminogen activator (rtPA) and bevacizumab in vitro because during surgery, rtPA or rtPA-induced plasmin may cleave and inactivate bevacizumab. METHODS To simulate the intraoperative range of mixing ratios of rtPA, bevacizumab, and subretinal blood, we calculated the volumes of 12 submacular hemorrhages (SHs) with a spherical cap formula using measurements derived from fundus photographs and spectral-domain optical coherence tomographic images. Bevacizumab was incubated with rtPA or plasmin before gel electrophoresis with Coomassie blue and silver staining. The anti-angiogenetic activity of bevacizumab in the presence of rtPA with or without clotted human blood or of plasmin was quantified by vascular endothelial growth factor–enzyme-linked immunosorbent assay after incubation with the supernatant of porcine retinal pigment epithelium cell cultures. RESULTS The mean (SD) volume of SH was 28.6 (24.7) mm3 (range, 6.2-94.6 mm3). In sodium dodecyl sulfate–polyacrylamid electrophoresis with Coomassie blue or silver staining, bevacizumab displayed characteristic patterns of protein bands. No additional fragments were detected in co-application of bevacizumab with either rtPA or plasmin. The anti-angiogenetic activity of bevacizumab remained unchanged in co-application with rtPA with or without blood or plasmin. CONCLUSIONS We demonstrated the absence of cleavage or functional inactivation of bevacizumab by rtPA in an in-vitro model of their intraoperative co-application as a treatment of SH. CLINICAL RELEVANCE In clinical practice, rtPA and bevacizumab can be co-applied as a treatment for neovascular age-related macular degeneration with SH to simultaneously clear SH and reduce choroidal new vessel activity.

Compatibility of recombinant tissue plasminogen activator (rtPA) and aflibercept or ranibizumab coapplied for neovascular age-related macular degeneration with submacular haemorrhage

Background/aims Subretinal coapplication of recombinant tissue plasminogen activator (rtPA) and vascular endothelial growth factor (VEGF)-antagonists is a new treatment option for age-related macular degeneration complicated by submacular haemorrhage. Here, we investigate the compatibility of rtPA and aflibercept or ranibizumab in vitro because intraoperatively, rtPA or rtPA-induced plasmin may cleave aflibercept or ranibizumab. Methods Aflibercept and ranibizumab, respectively, were incubated with rtPA or plasmin, separated in gel electrophoresis and stained with Coomassie or silver. The antiangiogenic activity of the VEGF-antagonists was quantified by VEGF-ELISA after incubation with the supernatant of primary porcine retinal pigment epithelium cell cultures. Results In electrophoresis, ranibizumab displayed no additional fragments when it was coapplied with rtPA or plasmin. Its VEGF-inhibiting efficacy remained unchanged in coapplication with rtPA with or without blood, or plasmin. rtPA did not cleave or functionally compromise aflibercept. When aflibercept was coapplied with plasmin, electrophoresis displayed additional bands in Coomassie (30 kDa, 27 kDa, 19 kDa, 15 kDa) and silver staining (31 kDa, 26 kDa, 21 kDa, 19 kDa, 15 kDa). While at a clinical dosage (800 µg/mL) VEGF was inhibited by aflibercept when coapplied with plasmin, at borderline concentrations (400 ng/mL) VEGF-binding ability of aflibercept was abolished. Conclusions Ranibizumab is not cleaved or functionally compromised by rtPA or plasmin. Aflibercept is cleaved and its VEGF-binding ability is reduced when coapplied with plasmin. In clinical practice, rtPA and ranibizumab can be coapplied as a treatment for neovascular age-related macular degeneration with submacular haemorrhage while the antiangiogenic activity of aflibercept may be compromised when coapplied with rtPA in the presence of plasmin.