Purpose To evaluate clinical outcome after surgery of idiopathic epiretinal membranes (ERM) with internal limiting membrane (ILM) peeling using a commercial combination of Brilliant blue G (BBG, 0.25 mg/ml) with 4% polyethylene glycol (PEG). Methods It was a prospective, single-center study. Macular surgery was performed due to ERM (n = 18) by two experienced surgeons. Exclusion criteria were secondary ERM, previous retinal surgery and pharmacological treatment. Best-corrected visual acuity (BCVA), optical coherence tomography (OCT), and multifocal ERG (RETIscan) were assessed at baseline and three months after surgery. Results The BCVA improved from baseline 0.4 ± 0.13 logMAR to 0.3 ± 0.2 logMAR after three months (p > 0.05). The mean central foveal thickness was reduced from 407 ± 85 μm to 366 ± 56 μm after three months (p > 0.05). At baseline, the mean P1 amplitude (nV/deg2) was 53.5 ± 32.1 in ring 1 and 35.9 ± 20.1 in ring 2. Three months after surgery the mean P1 amplitude was comparable with 57.2 ± 16.3 in ring 1 and 38.0 ± 11.7 in ring 2 compared with the initial situation (p = 0.22 and p = 0.3, respectively). Conclusion BBG with 4% PEG can be used for ILM peeling in patients with idiopathic epiretinal membranes without any sign of short-term toxicity.
Age related macular degeneration (AMD), retinitis pigmentosa, and other RPE related diseases are the most common causes for irreversible loss of vision in adults in industrially developed countries. RPE transplantation appears to be a promising therapy, as it may replace dysfunctional RPE, restore its function, and thereby vision. Here we describe a method for transplanting a cultured RPE monolayer on a scaffold into the subretinal space (SRS) of rabbits. After vitrectomy xenotransplants were delivered into the SRS using a custom made shooter consisting of a 20-gauge metallic nozzle with a polytetrafluoroethylene (PTFE) coated plunger. The current technique evolved in over 150 rabbit surgeries over 6 years. Post-operative follow-up can be obtained using non-invasive and repetitive in vivo imaging such as spectral domain optical coherence tomography (SD-OCT) followed by perfusion-fixed histology. The method has well-defined steps for easy learning and high success rate. Rabbits are considered a large eye animal model useful in preclinical studies for clinical translation. In this context rabbits are a cost-efficient and perhaps convenient alternative to other large eye animal models.
In the treatment of various retinal pigment epithelium (RPE) related retinal diseases, selective retina therapy (SRT) is highly demanded, as SRT intends to selectively damage the RPE while sparing the neurosensory retina (NSR) and the choroid. A gentle method for removing diseased host RPE cells is still missing regarding RPE stem cell therapy. Cell therapeutics for age-related macular degeneration are often implanted regardless of host RPE status in the target zone, which may result in RPE multilayering. Here, we study a novel laser for selective large-area RPE removal without damaging the surrounding tissue prior to RPE implantation to promote subretinal integration. Therefore, pigmented rabbit eyes were exposed to laser pulses of 8 μs in duration (wavelength, 532 nm; top-hat beam profile, 223 × 223 μm2). Postirradiation retinal changes were assessed with color fundus photography, fluorescein angiography, indocyanine green angiography, and optical coherence tomography (OCT). Here we present the histological outcome of four animals after laser treatment. Following euthanization, the eyes of the animals were processed for histology, sectioned in 5 μm paraffin sections and stained with hematoxylin and eosin. Particular emphasis was given to an OCT vs light microscopy comparison. Our results reveal that RPE can be removed selectively using laser pulses of 8 µs duration in the green spectral range without damaging the NSR. Therefore, this regime proves to be applicable in the sense of SRT.
<b>Background:</b> To investigate the risk of primary macular hole (MH) in the fellow eye, and to evaluate baseline characteristics and optical coherence tomography (OCT) features that precede MH formation in the fellow eye. <b>Methods:</b> A retrospective review of 229 patients treated for primary MH at Stavanger University Hospital, Norway, from January 2008 through December 2018. The patients were categorised into two groups according to subsequent development of MH in the fellow eye. The OCT findings of the two groups were compared, and associated risk factors for MH formation assessed. <b>Results:</b> Twenty cases of bilateral MH were identified. The overall bilateral disease risk was 8.8% (95% CI, 5.8–13.2%). Two patients were previously operated in the fellow eye, six patients presented with bilateral MH, and 12 patients subsequently developed MH in the fellow eye. The risk of subsequent MH development was 5.7% (95% CI, 3.3–9.8%). Although the extent of posterior vitreous detachment (PVD) tended to be more progressed in the bilateral group compared with the unilateral group, the difference was not statistically significant. In the bilateral group, 41.7% had outer retinal defects vs 6.6% in the unilateral group (p = 0.001), and 33.3% in the bilateral group had intraretinal pseudocysts vs 10.2% in the unilateral group (p = 0.036, not significant after multiple testing correction). <b>Conclusion:</b> Outer retinal defects and intraretinal pseudocysts are associated with an increased risk of MH formation in the fellow eye, and complete PVD indicates a decreased risk of MH formation.
Age related macular degeneration (AMD), retinitis pigmentosa, and other RPE related diseases are the most common causes for irreversible loss of vision in adults in industrially developed countries. RPE transplantation appears to be a promising therapy, as it may replace dysfunctional RPE, restore its function, and thereby vision.
Here we describe a method for transplanting a cultured RPE monolayer on a scaffold into the subretinal space (SRS) of rabbits. After vitrectomy xenotransplants were delivered into the SRS using a custom made shooter consisting of a 20-gauge metallic nozzle with a polytetrafluoroethylene (PTFE) coated plunger. The current technique evolved in over 150 rabbit surgeries over 6 years. Post-operative follow-up can be obtained using non-invasive and repetitive in vivo imaging such as spectral domain optical coherence tomography (SD-OCT) followed by perfusion-fixed histology.
The method has well-defined steps for easy learning and high success rate. Rabbits are considered a large eye animal model useful in preclinical studies for clinical translation. In this context rabbits are a cost-efficient and perhaps convenient alternative to other large eye animal models.
Abstract Background Human pluripotent stem cells (hPSCs) provide a promising cell source for retinal cell replacement therapy, but often lack standardized cell production and live-cell shipment logistics as well as rigorous analyses of surgical procedures for cell transplantation in delicate macula area. We have previously established a xeno- and feeder cell-free production system for hPSC differentiated retinal pigment epithelial (RPE) cells and herein, a novel immunosuppressed non-human primate (NHP) model with a disrupted ocular immune privilege is presented for transplanting human embryonic stem cell (hESC)-derived RPE on a scaffold, and the safety and submacular graft integration are assessed. Furthermore, the feasibility of intercontinental shipment of live hESC-RPE is examined. Methods Cynomolgus monkeys were systemically immunosuppressed and implanted with a hESC-RPE monolayer on a permeable polyester-terephthalate (PET) scaffold. Microscope integrated intraoperative optical coherence tomography (miOCT) guided surgery; postoperative follow-up incorporated scanning laser ophthalmoscopy, spectral domain (SD-) OCT, and full-field electroretinography (ERG) were used as outcome measures. In addition, histology was performed after 28-days follow-up. Results Intercontinental cell shipment, which took > 30 hours from the manufacturing to the transplantation site, did not alter the hESC-RPE quality. The submacular hESC-RPE xenotransplantation was performed in 11 macaques. The miOCT typically revealed foveal disruption. ERG showed amplitude and peak time preservation in cases with favorable surgical outcome. Histology confirmed photoreceptor preservation above the grafts and in vivo phagocytosis by hESC-RPE, albeit evidence of cytoplasmic redistribution of opsin in photoreceptors and glia hypertrophy. The immunosuppression protocol efficiently suppressed retinal T-cell infiltration and microglia activation. Conclusion These results suggest both structural and functional submacular integration of hESC-RPE xenografts. It is anticipated that surgical technique refinement will further improve engraftment of macular cell therapeutics with significant translational relevance to improve future clinical trials.
Zusammenfassung Hintergrund Aufkommende Therapien führen zu wachsendem Interesse an hereditären Netzhauterkrankungen (engl. „inherited retinal diseases“ [IRDs]), einer heterogenen Gruppe seltener Erkrankungen, die potenziell zur Erblindung führen. Aktuell sind nur unzureichend systematische Studien zur Demografie und zum Management der IRDs in deutschen augenärztlichen Einrichtungen vorhanden. Ziele der Arbeit Charakterisierung der Versorgung von IRD-Patient*innen in Deutschland, Erfassung von Daten zur Diagnostik, zur systematischen Speicherung der Patient*innendaten und zur Weiterbildung in Ophthalmogenetik. Methoden Die anonyme Umfrage mittels Online-Fragebogen (SoSci Survey GmbH) wurde an alle deutschen Augenkliniken (Quelle: Deutsche Ophthalmologische Gesellschaft) und 3 IRD-Schwerpunktpraxen versandt. Der für die Umfrage entwickelte Katalog bestand aus 69 Fragen. Ergebnisse Die Antwortquote betrug 44,8 %. Fast alle Einrichtungen (93,6 %) gaben an, IRD-Patient*innen zu betreuen, jedoch unterscheiden sich universitäre und nichtuniversitäre Kliniken stark in der Patient*innenzahl. Datenbanken wurden in 60 % der universitären (UK) und 5,9 % der nichtuniversitären Kliniken (NUK) genutzt. Die Hälfte (53 %) der NUKs und 12 % der UKs gaben an, dass weniger als 20 % der betreuten Patient*innen eine molekulargenetische Diagnose erhielten. Die Antworten der Schwerpunktpraxen ähnelten denen der UKs. Patient*innen mit der mittels Voretigen Neparvovec therapierbaren RPE65 -mutationsassoziierten IRD wurden in 9 UKs betreut. Diskussion Die Umfrage zeigt Defizite in der Versorgung von IRDs auf. Insbesondere war der Prozentsatz von Betroffenen mit bekanntem Genotyp zwischen UKs und NUKs sehr unterschiedlich. Hier sollten gerade wegen der aufkommenden Therapien Verbesserungen initiiert werden.
