Clinical outcomes of the PAUL® glaucoma implant: One-year results.

BACKGROUND: To report one-year outcomes from a single-centre cohort undergoing PAUL® Glaucoma Implant (PGI) surgery. METHODS: Retrospective review of patients undergoing PGI surgery at the University Eye Hospital Bonn, Germany, from April 2021 to September 2021. RESULTS: Forty-five eyes of 41 patients were included. Qualified and complete success rates (95% CI) were 95.6% (88.9%-100%) and 73.3% (60%-86.7%) for Criterion A (IOP ≤ 21 mmHg), 84.4% (73.3%-93.3%) and 74.4% (51.1%-80.0%) for Criterion B (IOP ≤ 18 mmHg), 62.2% (48.9%-75.6%) and 46.7% (31.2%-62.2%) for Criterion C (IOP ≤ 15 mmHg) and 26.7% (13.3%-40.0%) and 22.2% (11.1%-33.3%) for Criterion D (IOP ≤ 12 mmHg), respectively. Mean IOP decreased from 26.1 mmHg (7-48 mmHg) to 12.0 mmHg (3-24 mmHg) (reduction of 48.83%) after 12 months with a reduction of IOP-lowering agents from 0.5 (0-3). One eye (2.2%) needed an injection of viscoelastic due to significant hypotony with AC shallowing, and four eyes (8.9%) developed choroidal detachments due to hypotony which resolved without further interventions after 6 weeks. Three patients (6.7%) developed tube exposure which required conjunctival revision with an additional pericardial patch graft. An intraluminal prolene stent was removed in 19 eyes (42.2%) after a mean time period of 8.4 months (2-12 m). Mean IOP before the removal was 21.9 mmHg (12-38 mmHg) and decreased to 11.3 mmHg (6-16 mmHg). CONCLUSIONS: PGI surgery is an effective procedure for reducing IOP and pressure-lowering therapy. An intraluminal prolene stent impedes hypotony in the early postoperative phase and enables further IOP lowering without additional interventions during the postoperative course.

A nanofibrillar surface promotes superior growth characteristics in cultured human retinal pigment epithelium.

BACKGROUND: To evaluate the influence of surface topography on the proliferation of the retinal pigment epithelium (RPE) by comparing nanofibrillar and smooth substrates. METHODS: Electrospun polyamide nanofibers (EPN) are an engineered surface mimicking native basement membranes. Commonly used plastic (polystyrene, PS) and glass substrates have a smooth topography. All were analyzed by scanning electron microscopy. RPE cultures were established from fetal and adult donors. Growth curves were established on the above substrates. Cell cycle and growth fractions were analyzed with 5-ethynyl-2'-deoxyuridine (EdU) and 4',6-diamidino-2-phenylindole (DAPI). RESULTS: At a magnification of ×5,000, EPN showed randomly overlapping fibers and pores. The surface of glass was slightly studded yet regular, in contrast to ideally smooth PS. Polygonal cells grew on nanofibers in a colony-like distribution, while randomly spread spindle-shaped cell morphologies were seen on smooth surfaces. This was observed at all donor ages. Initial proliferation rates were higher on EPN, and similar final cell densities were reached in all age groups, compared to an age-related decline on PS. EdU/DAPI revealed faster cell cycles on EPN. Growth fractions were higher and maintained longer on EPN. Observed substrate differences in growth behavior were statistically significant. CONCLUSION: Surface topography appears to induce distinct RPE proliferation characteristics.

Silicone oil tamponade for persistent macular holes.

BACKGROUND: A variety of treatment strategies have been proposed for macular holes that persist or recur after surgery, and the debate about the best re-treatment approach is ongoing. To allow for a comparison with alternative surgical therapies, we assessed the anatomical and functional outcome of a temporary tamponade with conventional silicone oil in persistent or recurrent full-thickness macular holes. METHODS: We retrospectively investigated consecutive patients with full-thickness macular holes that persisted or recurred following vitrectomy with internal limiting membrane peeling and gas tamponade. All patients received re-treatment by temporary tamponade of silicone oil and were allowed free postoperative positioning. Anatomical closure rate was assessed by optical coherence tomography, and change of best-corrected visual acuity (BCVA) was analyzed. RESULTS: A total of 33 eyes of 33 consecutive patients were included. Macular hole closure following silicone oil tamponade was achieved in 30 of 33 eyes (90.9%). Median BCVA improved from 1.00 logMAR (interquartile range, 0.60-1.00) to 0.65 logMAR (0.49-1.00; p = 0.010) after silicone oil removal. In patients with macular hole closure, 61.3% exhibited functional improvement with median BCVA changing from 1.00 logMAR (0.70-1.00) to 0.60 logMAR (0.49-1.00; p = 0.0005). Mean minimal linear diameter of macular holes before primary surgery was 391.0 µm (±137.8; range 133-630), and 48.5% of macular holes were >400 µm in diameter. CONCLUSIONS: Treatment of persistent or recurrent full-thickness macular holes by temporary conventional silicone oil tamponade without postoperative positioning results in a high closure rate and a significant mean improvement of visual acuity.

Survival and functionality of xeno-free human embryonic stem cell-derived retinal pigment epithelial cells on polyester substrate after transplantation in rabbits.

PURPOSE: To study immunogenic properties of human embryonic stem cell-derived retinal pigment epithelium (hESC-RPE) and to evaluate subretinal xenotransplantation of hESC-RPE on porous polyethylene terephthalate (PET) in rabbits. METHODS: Human ESC-RPE cells were characterized by morphology, transepithelial electrical resistance (TER), protein expression and photoreceptor outer segment phagocytosis in vitro. Expression of major histocompatibility complex (MHC) proteins was assessed in conventionally or xeno-free produced hESC-RPE ± interferon-gamma (IFN-γ) stimulation (n = 1). Xeno-free hESC-RPE on PET with TER < 200 Ω·cm2  > or PET alone were transplanted into 18 rabbits with short-term triamcinolone ± extended tacrolimus immunosuppression. Rabbits were monitored by spectral domain optical coherence tomography. After 4 weeks, the eyes were processed for histology and transmission electron microscopy. RESULTS: Upon in vitro IFN-γ stimulation, xeno-free hESC-RPE expressed lower level of MHC-II proteins compared to the conventional cells. Outer nuclear layer (ONL) atrophy was observed over the graft in most cases 4 weeks post-transplantation. In 3/4 animals with high TER hESC-RPE, but only in 1/3 animals with low TER hESC-RPE, ONL atrophy was observed already within 1 week. Retinal cell infiltrations were more frequent in animals with high TER hESC-RPE. However, the difference was not statistically significant. In three animals, preservation of ONL was observed. Weekly intravitreal tacrolimus did not affect ONL preservation. In all animals, hESC-RPE cells survived for 4 weeks, but without tacrolimus, enlarged vacuoles accumulated in hESC-RPE (n = 1). CONCLUSIONS: Xenografted xeno-free hESC-RPE monolayers can survive and retain some functionality for 4 weeks following short-term immunosuppression. The preliminary findings of this study suggest that further investigations to improve transplantation success of hESC-RPE xenografts in rabbits should be addressed especially toward the roles of hESC-RPE maturation stage and extended intravitreal immunosuppression.

Enhancement of retinal pigment epithelial culture characteristics and subretinal space tolerance of scaffolds with 200 nm fiber topography.

Tissue engineered retinal pigment epithelial (RPE) transplantation is a promising cell-based therapy for age-related macular degeneration. The aim of this work is to develop a supportive scaffold with a favorable topography to aid functional RPE monolayer maintenance while being tolerated underneath the retina. To this end, films and electrospun substrates with fiber diameters ranging from 200 to 1000 nm were made of polyethylene terephthalate or poly(L-lactide-co-ε-caprolactone), and then tested using human fetal RPE cells in vitro and transplanted subretinally in rabbits. The results indicated that RPE on both 200 nm fiber variants showed the highest cell densities, adherent monolayers achieved deeper pigmentation, and more uniform hexagonal tight junctions. Facile subretinal implantation of flat 200 nm fiber membranes was achieved by electrospinning them onto a porous rigid-elastic carrier. Spectral-domain optical coherence tomography showed a reattached, slightly thinned retina overlying the implants over 2 weeks observation. Histology demonstrated native RPE variably migrated onto the nanofibers, and a reactive gliosis with some photoreceptor degeneration. In conclusion, scaffolds with 200 nm fiber topography enhanced RPE culture, showed subretinal biocompatibility, and should thus be considered for future cell-based therapies in blinding retinal diseases.

Human RPE stem cells grown into polarized RPE monolayers on a polyester matrix are maintained after grafting into rabbit subretinal space.

Transplantation of the retinal pigment epithelium (RPE) is being developed as a cell-replacement therapy for age-related macular degeneration. Human embryonic stem cell (hESC) and induced pluripotent stem cell (iPSC)-derived RPE are currently translating toward clinic. We introduce the adult human RPE stem cell (hRPESC) as an alternative RPE source. Polarized monolayers of adult hRPESC-derived RPE grown on polyester (PET) membranes had near-native characteristics. Trephined pieces of RPE monolayers on PET were transplanted subretinally in the rabbit, a large-eyed animal model. After 4 days, retinal edema was observed above the implant, detected by spectral domain optical coherence tomography (SD-OCT) and fundoscopy. At 1 week, retinal atrophy overlying the fetal or adult transplant was observed, remaining stable thereafter. Histology obtained 4 weeks after implantation confirmed a continuous polarized human RPE monolayer on PET. Taken together, the xeno-RPE survived with retained characteristics in the subretinal space. These experiments support that adult hRPESC-derived RPE are a potential source for transplantation therapies.

Subretinal delivery of ultrathin rigid-elastic cell carriers using a metallic shooter instrument and biodegradable hydrogel encapsulation.

PURPOSE: To develop a surgical technique for the subretinal implantation of cell carriers suitable for the transplantation of cultured retinal pigment epithelium (RPE) in a preclinical animal model. METHODS: Cell carriers were porous 10-µm-thick polyester membranes. A custom-made shooter instrument consisted of a 20-gauge metallic nozzle with a nonstick plunger. Fetal human RPE cultures were used for vitality assessment during instrument handling. Transvitreal subretinal implantation of carriers without RPE was performed in 31 rabbits after vitrectomy. Fourteen of 31 implants were encapsulated in gelatin. Fluid turbulence over the implantation site was minimized using a novel infusion cannula. Six rabbits had intravitreal plasmin injections before surgery. SD-OCT in vivo images were obtained after 3, 7, and 14 days, followed by perfusion-fixed histology. RESULTS: Gelatin encapsulation of RPE/polyester implants made cell loss during handling reproducible, compared with 40% of controls showing random, large damage zones. Gelatin implants were ejected smoothly in 12 of 14 surgeries (86%), whereas "naked" implants frequently became trapped with the instrument, which reduced success to 9 of 17 cases (53%). Vitreous remnants after vitrectomy alone complicated subretinal placement of encapsulated and naked implants in 7 of 25 cases (28%). Plasmin-assisted vitrectomy resulted in implant ejection unperturbed by vitreous adhesions in six experiments. SD-OCT and histology demonstrated atraumatic subretinal implant delivery after uncomplicated surgery. CONCLUSIONS: A novel shooter instrument design allows for safe and atraumatic transvitreal delivery of hydrogel-encapsulated, ultrathin, rigid-elastic carriers into the subretinal space. The procedure may be used in the future to deliver cultured RPE.