Regenerative Retinal Laser and Light Therapies (RELITE): Proposal of a New Nomenclature, Categorization, and Trial Reporting Standard.

Objectives: Numerous laser and light therapies have been developed to induce regenerative processes in the choroid/retinal pigment epithelium (RPE)/photoreceptor complex, leaving the neuroretina undamaged. These therapies are applied to the macula for the treatment of various diseases, most prominently diabetic maculopathy, retinal vein occlusion, central serous chorioretinopathy, and age-related macular degeneration. However, the abundance of technologies, treatment patterns, and dosimetry protocols has made understanding these therapies and comparing different approaches increasingly complex and challenging.

[OCT biomarkers in diabetic maculopathy and artificial intelligence].

Diabetes mellitus is a chronic disease the microvascular complications of which include diabetic retinopathy and maculopathy. Diabetic macular edema, proliferative diabetic retinopathy, and diabetic macular ischemia pose a threat to visual acuity. Artificial intelligence can play an increasingly more important role in making the diagnosis and the treatment regimen of maculopathies in everyday clinical practice in the future.

A rabbit model for outer retinal atrophy caused by surgical RPE removal.

Purpose: We aimed to establish a rabbit model with retinal atrophy induced by an iatrogenic retinal pigment epithelium (RPE) removal, for future testing of the efficacy and safety of cell therapy strategies.

Methods: A localized detachment of the retina from the RPE/choroid layer was created in 18 pigmented rabbits. The RPE was removed by scraping with a custom-made extendable loop instrument.

[Prospective noninterventional BLUE SKY study evaluating the efficacy of brolucizumab in treatment-naïve and previously treated patients with neovascular AMD].

Intravitreal injection of anti-vascular endothelial growth factor (VEGF) is the standard treatment for patients with neovascular age-related macular degeneration (nAMD). In addition to the approved substances ranibizumab (Lucentis®, Novartis) and aflibercept (Eylea®, Bayer), bevacizumab (Avastin®, Roche) is also available. Furthermore, brolucizumab (Beovu®, Novartis) has been approved and has been available in Germany since April 2020.

Safety and effectiveness of pre-emptive diabetic vitrectomy in patients with severe, non-fibrotic retinal neovascularisation despite panretinal photocoagulation.

Objectives: To investigate the safety and effectiveness of pre-emptive vitrectomy in eyes with severe non-fibrotic proliferative diabetic retinopathy.

Methods: A multi-centre, retrospective, observational study. Pre-emptive vitrectomy was performed in non-fibrotic diabetic eyes with a visual acuity (VA) of 20/50 or better, where there was extensive persistent neovascularisation despite prior panretinal photocoagulation, and where the fellow eye had established sight loss despite vitrectomy for tractional complications.

Sodium-Iodate Injection Can Replicate Retinal Degenerative Disease Stages in Pigmented Mice and Rats: Non-Invasive Follow-Up Using OCT and ERG.

Purpose: The lack of suitable animal models for (dry) age-related macular degeneration (AMD) has hampered therapeutic research into the disease, so far. In this study, pigmented rats and mice were systematically injected with various doses of sodium iodate (SI). After injection, the retinal structure and visual function were non-invasively characterized over time to obtain in-depth data on the suitability of these models for studying experimental therapies for retinal degenerative diseases, such as dry AMD.

Selective Large-Area Retinal Pigment Epithelial Removal by Microsecond Laser in Preparation for Cell Therapy.

Purpose: Cell therapy is a promising treatment for retinal pigment epithelium (RPE)-associated eye diseases such as age-related macular degeneration. Herein, selective microsecond laser irradiation targeting RPE cells was used for minimally invasive, large-area RPE removal in preparation for delivery of retinal cell therapeutics.

Methods: Ten rabbit eyes were exposed to laser pulses 8, 12, 16, and 20 µs in duration (wavelength, 532 nm; top-hat beam profile, 223 × 223 µm²).

Submacular integration of hESC-RPE monolayer xenografts in a surgical non-human primate model.

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 the 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.

Retinal Pigment Epithelium Transplantation in a Non-human Primate Model for Degenerative Retinal Diseases.

Retinal pigment epithelial (RPE) transplantation holds great promise for the treatment of inherited and acquired retinal degenerative diseases. These conditions include retinitis pigmentosa (RP) and advanced forms of age-related macular degeneration (AMD), such as geographic atrophy (GA). Together, these disorders represent a significant proportion of currently untreatable blindness globally.

Persistent macular holes - what is the best strategy for revision?

Purpose: This study aims to analyze the success rate and functional outcome after revision surgery of persistent idiopathic full-thickness macular holes in a large patient cohort and to identify the optimal tamponade strategy and the value of new adjunctive manipulation techniques for persistent macular hole (pMH) closure.

Methods: Retrospective, comparative, non-consecutive case series of all revisional surgeries for idiopathic pMH between 2011 and 2019 at the Eye Clinic Sulzbach were identified. Of 1163 idiopathic MH surgeries, 74 eyes of 74 patients had pMH.

Hints for Gentle Submacular Injection in Non-Human Primates Based on Intraoperative OCT Guidance.

Purpose: Delivery of Advanced Therapy Medicinal Products to the submacular space is increasingly evolving into a therapeutic modality. Cell replacement for age-related macular degeneration (AMD) and gene therapy for RPE65 are recent successful examples. Herein, a nonhuman primate (NHP) model was used to investigate surgical means to detach the macula.

Surgical Transplantation of Human RPE Stem Cell-Derived RPE Monolayers into Non-Human Primates with Immunosuppression.

Recent trials of retinal pigment epithelium (RPE) transplantation for the treatment of disorders such as age-related macular degeneration have been promising. However, limitations of existing strategies include the uncertain survival of RPE cells delivered by cell suspension and the inherent risk of uncontrolled cell proliferation in the vitreous cavity. Human RPE stem cell-derived RPE (hRPESC-RPE) transplantation can rescue vision in a rat model of retinal dystrophy and survive in the rabbit retina for at least 1 month.

Subretinal Injection Under Perfluorocarbon Liquids to Avoid Foveal Dehiscence.

Summary: We describe a novel technique modification of subretinal injection to reduce the risk of foveal dehiscence during subretinal tissue plasminogen activator delivery for submacular haemorrhage, using a perfluorocarbon liquid filled vitreous cavity and an eccentric injection point, with a viscous fluid injector system controlled injection.

Purpose: To describe a novel method of subretinal injection to reduce the risk of foveal dehiscence during subretinal tissue plasminogen activator delivery for submacular hemorrhage.

Method: Description of technique with illustrative case description and details of four cases treated.

Alginate- and Hyaluronic Acid-Based Hydrogels as Vitreous Substitutes: An In Vitro Evaluation.

Purpose: To study alginate- and hyaluronic acid-based hydrogels in vitro as vitreous substitutes.

Methods: Biopolymeric hydrogels based on high-molecular alginate (0.5% and 1.

Publisher Correction: The choice of biopolymer is crucial to trigger angiogenesis with vascular endothelial growth factor releasing coatings.

A Correction to this paper has been published: https://doi.org/10.1007/s10856-020-06463-w.

The choice of biopolymer is crucial to trigger angiogenesis with vascular endothelial growth factor releasing coatings.

Bio-based coatings and release systems for pro-angiogenic growth factors are of interest to overcome insufficient vascularization and bio-integration of implants. This study compares different biopolymer-based coatings on polyethylene terephthalate (PET) membranes in terms of coating homogeneity and stability, coating thickness in the swollen state, endothelial cell adhesion, vascular endothelial growth factor (VEGF) release and pro-angiogenic properties. Coatings consisted of carbodiimide cross-linked gelatin type A (GelA), type B (GelB) or albumin (Alb), and heparin (Hep), or they consisted of radically cross-linked gelatin methacryloyl-acetyl (GM5A5) and heparin methacrylate (HepM5).

[Closure of Persisting Full Thickness Macular Holes by Subretinal Fluid Application: Technical Approach and Surgical Considerations].

Introduction: Firm adhesions between the retina and adjacent retinal pigment epithelium (RPE) may prevent the closure of macular holes (MH) after chromovitrectomy. Controlled application of subretinal (SR) fluid with BSS may release these adhesions leading to closure of the retracted retina in large and or refractory macular holes.

Methods: For a standardized procedure, it is recommended to exclude residues of epiretinal membranes on the retinal surface preoperatively at OCT or intraoperatively by means of vital dyes.

Surgical Approaches for Cell Therapeutics Delivery to the Retinal Pigment Epithelium and Retina.

Developing successful surgical strategies to deliver cell therapeutics to the back of the eye is an essential pillar to success for stem cell-based applications in blinding retinal diseases. Within this chapter, we have attempted to gather all key considerations during preclinical animal trials.Guidance is provided for choices on animal models, options for immunosuppression, as well as anesthesia.

[Acute macular neuroretinopathy in a 13-year-old female patient with focal choroidal excavation and pachychoroid disease].

Acute macular neuroretinopathy (AMN) is a rare disease that causes sudden onset of paracentral scotomas. The current case report describes a 13-year-old girl with AMN adjacent to a focal choroidal excavation (FCE) with pachychoroidal features. The patient was followed for 20 months and examined with multimodal imaging.