Prevention of Sunlight-Induced Cell Damage by Selective Blue-Violet-Light-Filtering Lenses in A2E-Loaded Retinal Pigment Epithelial Cells.

Blue light accelerates retinal aging. Previous studies have indicated that wavelengths between 400 and 455 nm are most harmful to aging retinal pigment epithelia (RPE). This study explored whether filtering these wavelengths can protect cells exposed to broad sunlight. Primary porcine RPE cells loaded with 20 µM A2E were exposed to emulated sunlight filtered through eye media at 1.8 mW/cm2 for 18 h. Filters selectively filtering out light over 400-455 nm and a dark-yellow filter were interposed. Cell damage was measured by apoptosis, hydrogen peroxide (H2O2) production, and mitochondrial membrane potential (MMP). Sunlight exposure increased apoptosis by 2.7-fold and H2O2 by 4.8-fold, and halved MMP compared to darkness. Eye Protect SystemTM (EPS) technology, filtering out 25% of wavelengths over 400-455 nm, reduced apoptosis by 44% and H2O2 by 29%. The Multilayer Optical Film (MOF), at 80% of light filtered, reduced apoptosis by 91% and H2O2 by 69%, and increased MMP by 73%, overpassing the dark-yellow filter. Photoprotection increased almost linearly with blue-violet light filtering (400-455 nm) but not with total blue filtering (400-500 nm). Selective filters filtering out 25% (EPS) to 80% (MOF) of blue-violet light offer substantial protection without affecting perception or non-visual functions, making them promising for preventing light-induced retinal damage with aesthetic acceptance for permanent wear.

Lessons learned from the RE(ACT) conference on medical devices for rare diseases.

The field of rare disease therapeutics has witnessed significant growth in recent years, highlighting the need for diverse therapeutic approaches to cater to the unique needs of individuals with rare diseases. Rare disease therapies encompass a broad spectrum of interventions, including orphan medicinal products, orphan medical devices, rehabilitative therapies, and digital therapeutics, with the lines between these categories blurring. This paper covers the session of the RE (ACT)-IRDiRC Conference 2023 and delves into the landscape of orphan medical device research and development, shedding light on the challenges and opportunities in this burgeoning field. It provides a short overview of the different international legislations in the field. In addition, it highlights several exemplary orphan medical devices. The first example is an exoskeleton for boys with Duchenne Muscular Dystrophy, enabling them to maintain arm functionality and independence. Another example presented was an EEG device linked to an app detecting seizures in rare epilepsy conditions, which alerts caregivers to seizures in real-time but also facilitates objective seizure reporting for clinicians, aiding in diagnosis and treatment optimization. It also showcases the role of gamification and enabling technologies in addressing rare diseases, by showing a game designed for children with cystic fibrosis, and a telemedicine system for rehabilitation therapy. Both solutions aim to improve patients' understanding of their conditions and enhance their self-management. In conclusion, this paper underscores the critical need for patient-centric orphan and pediatric medical devices to provide therapeutic options for individuals with rare diseases. It highlights the impact of existing devices on enhancing the quality of life for rare disease patients and emphasizes the necessity for greater incentives and support for research and development in this field.

Meta-analysis of treatment outcomes for patients with m.11778G>A MT-ND4 Leber Hereditary Optic Neuropathy.

Our aim was to assess the visual outcomes of patients with Leber hereditary optic neuropathy (LHON) harboring the m.11778G>A MT-ND4 mutation who had no treatment (natural history) or received idebenone or lenadogene nolparvovec. Efficacy outcomes included clinically relevant recovery (CRR) from nadir and final best-corrected visual acuity (BCVA). For the natural history and idebenone groups, we performed a systematic review of the literature and available clinical/regulatory reports. For the lenadogene nolparvovec group, all data from phase 3 studies were included. The overall effect and its 95% confidence interval (CI) were estimated using a random effects model. For each meta-analysis, patients had a mean age of approximately 30 years at vision loss and were mostly (≥78%) men. The CRR from nadir [95% CI] at eye level was 17% [7%; 30%] (n=316 eyes), 31% [24%; 40%] (n=313) and 59% [54%; 64%] (n=348) in untreated, idebenone-treated and lenadogene nolparvovec-treated patients, respectively. This gradient of efficacy was also observed with CRR at the patient level and final BCVA. There was a gradient of efficacy in all assessed visual outcomes, more marked for CRR than for final BCVA, with lenadogene nolparvovec gene therapy superior to idebenone treatment, and both superior to the natural history of the disease.

Geographic atrophy progression secondary to age-related macular degeneration: Five years of follow-up.

PURPOSE: To study the progression of geographic atrophy (GA) secondary to age-related macular degeneration over a five-year follow-up. METHODS: Eyes with GA included to assess demographic data, yearly optical coherence tomography (OCT) findings and the GA growth rate on infra-red (IR) images. RESULTS: A total of 41 eyes of 29 patients were included with a mean age of 81.76 ± 6.37 at baseline, and 65.51% were females. Over five years, there was a significant increase in the mean GA area from 8.44 ± 8.98 mm² to 13.32 ± 10.07 mm² (P < 0.001), with an annual growth rate of 1.14 ± 0.78 mm². The annual growth rates in females were slightly higher compared to males (1.29 ± 0.89 mm2 vs 0.96 ± 0.49 mm2, p = 0.569), and in smokers was slightly higher than non-smokers (1.35 ± 0.85 mm2 vs 0.94 ± 0.66 mm2, p = 0.100). Larger GA areas at the baseline showed higher GA progression in mm2 per year (P = 0.04). Smaller GA areas and fovea-spared GA at the baseline exhibited a larger percentage increase (P < 0.001 and P = 0.015, respectively). There was a lower GA progression rate in eyes with outer retinal tubulations (ORT) (P = 0.027), yet no significant correlation was found between GA progression and other OCT features. CONCLUSIONS: Smaller, fovea-sparing GA eyes experienced a more substantial proportional increase over five years. Also, The presence of ORT was associated with a slower rate of GA progression. Additionally, we observed a trend of faster GA growth in smokers and female genders.

Endpoints and Design for Clinical Trials in USH2A-Related Retinal Degeneration: Results and Recommendations From the RUSH2A Natural History Study.

Purpose: To evaluate functional and structural assessments as endpoints for clinical trials for USH2A-related retinal degeneration. Methods: People with biallelic disease-causing variants in USH2A, visual acuity ≥ 20/80, and visual field ≥ 10° diameter were enrolled in a 4-year, natural history study. Participants underwent static perimetry, microperimetry, visual acuity, fullfield stimulus testing (FST), and optical coherence tomography annually. Rates of change estimated from mixed-effects linear models and percentages of eyes with changes exceeding the coefficient of repeatability (CoR) or thresholds conforming with U.S. Food and Drug Administration (FDA) guidelines were evaluated. Results: Rates of change were generally more sensitive to change than proportions of eyes exceeding a threshold such as the CoR. Baseline ellipsoid zone area ≥ 3 mm2 was necessary to detect change. Mean sensitivity and volumetric hill of vision measures on static perimetry had similar properties and were the most sensitive to changes of the continuous measures. The highest 4-year proportions of eyes exceeding the CoR were from FST testing (47%) and microperimetry (32%). Specification of loci as functional transition points (FTPs) resulted in 45% (static perimetry) and 46% (microperimetry) at 4 years, meeting FDA guidelines for progression. Conclusions: Rate of change of mean sensitivity on static perimetry was a sensitive perimetric continuous measure. Percentages of within-eye change were largest with FST testing and microperimetry. FTPs appear to be particularly sensitive to change. These results affect clinical trial design for USH2A-related retinal degeneration. Translational Relevance: Analyses of natural history data from the Rate of Progression in USH2A-Related Retinal Degeneration (RUSH2A) study can inform eligibility criteria and endpoints for clinical trials.

Loss of ON-Pathway Function in Mice Lacking Lrit3 Decreases Recovery From Lens-Induced Myopia.

Purpose: To determine whether the Lrit3-/- mouse model of complete congenital stationary night blindness with an ON-pathway defect harbors myopic features and whether the genetic defect influences the recovery from lens-induced myopia. Methods: Retinal levels of dopamine (DA) and 3,4 dihydroxyphenylacetic acid (DOPAC) from adult isolated Lrit3-/- retinas were quantified using ultra performance liquid chromatography after light adaptation. Natural refractive development of Lrit3-/- mice was measured from three weeks to nine weeks of age using an infrared photorefractometer. Susceptibility to myopia induction was assessed using a lens-induced myopia protocol with -25 D lenses placed in front of the right eye of the animals for three weeks; the mean interocular shift was measured with an infrared photorefractometer after two and three weeks of goggling and after one and two weeks after removal of goggles. Results: Compared to wild-type littermates (Lrit3+/+), both DA and DOPAC were drastically reduced in Lrit3-/- retinas. Natural refractive development was normal but Lrit3-/- mice showed a higher myopic shift and a lower ability to recover from induced myopia. Conclusions: Our data consolidate the link between ON pathway defect altered dopaminergic signaling and myopia. We document for the first time the role of ON pathway on the recovery from myopia induction.

ADAPTIVE OPTICS AND MULTIMODAL IMAGING FOR INFLAMMATORY VITREORETINAL INTERFACE ABNORMALITIES.

PURPOSE: To investigate changes to the vitreoretinal interface in uveitis with multimodal imaging including adaptive optics. METHODS: Four eyes (four patients) affected by fovea-attached (subtype 1A) or fovea-sparing epiretinal membranes (ERMs) on spectral-domain optical coherence tomography or visible internal limiting membrane (ILM) on infrared scanning laser ophthalmoscope (SLO) fundus imaging were recruited in this pilot study. The microstructure of the vitreoretinal interface was imaged using flood-illumination adaptive optics (FIAO), and the images were compared with the cross-sectional spectral-domain optical coherence tomography data. RESULTS: Adaptive optics images revealed multiple abnormalities of the vitreoretinal interface, such as deep linear striae in ERM, and hyperreflective microstructures at the location of ERMs and ILMs. The cone mosaic was imaged by FIAO and was found altered in the four eyes with ERMs or visible ILM. The same four eyes presented alteration of photopic 30 Hz flicker that was reduced in amplitude indicating cone inner retinal layer dysfunction. CONCLUSION: FIAO imaging can identify specific patterns associated with ERMs and ILMs. Correlating FIAO imaging of the vitreomacular interface with the structural alterations seen in FIAO at the level of the outer retinal structures can help understand the cause of significant macular dysfunction associated with ERM.

Incidence and risk factors of fellow-eyes wet conversion in unilateral neovascular age-related macular degeneration over 15-year follow-up.

PURPOSE: Incidence and risk factors of fellow eye wet conversion in unilateral neovascular age-related macular degeneration (nAMD) over 15-years follow-up. METHODS: This retrospective study reviewed 593 unilateral nAMD patients with a minimum of five years up to 15 years of follow-up. The demographic data, visual acuity, fellow eye nAMD conversion rate, and the number of anti-vascular endothelial growth factor (anti-VEGF) injections in the primary eye were evaluated. Also, the nAMD-converted fellow eyes were divided into two groups based on the time of conversion (less and more than two years from the first injection in the primary eye). Based on the data types, the T-test, Chi-square, and Mann-Whitney U test were used to analyze. RESULTS: The total cases were 593 patients, and 248 eyes (41.82%) converted to nAMD in the mean interval of 34.92 ± 30.62 months. The males exhibited a predisposition to wet conversion at 2.54 years earlier than their female counterparts (P = 0.025). In all the converted fellow eyes, the mean age was 2.3 years higher at presentation in the group who converted within two years of follow-up in compared to eyes that converted after two years (79.82 ± 8.64 vs 77.51 ± 8.5 years, P = 0.035). Additionally, eyes converting within two years had a mean baseline LogMAR visual acuity of 0.44 ± 0.47, compared to 0.32 ± 0.41 for conversions after two years (P = 0.014). CONCLUSION: This study reported that males showed a predisposition to fellow eye nAMD conversion at an earlier age. Additionally, there was a trend of faster fellow eye nAMD conversion in individuals with higher age and lower baseline visual acuity. KEY MESSAGES: What is known • Certain risk factors may make the fellow eye of neovascular age-related macular degeneration (nAMD) more likely to progress to wet conversion. • Identifying these risk factors for fellow eye wet conversion can help prevent it, potentially preserving the patient's vision quality for a longer duration. • The studies on the incidence of wet conversion in the fellow eye have yielded controversial results. What is new • During the 15-year follow-up period, nearly half (47.58%) of the fellow eyes that underwent wet conversion did so within the initial two years following the wet conversion of the first eye. • Males showed a predisposition to fellow eye nAMD conversion at an earlier age. • There was a trend of faster fellow eye nAMD conversion in individuals with higher age and lower baseline visual acuity.

DRD2 activation inhibits choroidal neovascularization in patients with Parkinson's disease and age-related macular degeneration.

Neovascular age-related macular degeneration (nAMD) remains a major cause of visual impairment and puts considerable burden on patients and health care systems. l-DOPA-treated Parkinson's disease (PD) patients have been shown to be partially protected from nAMD, but the mechanism remains unknown. Using murine models that combine 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced (MPTP-induced) PD and laser-induced nAMD with standard PD treatment of l-DOPA/DOPA-decarboxylase inhibitor or specific dopamine receptor inhibitors, we here demonstrate that l-DOPA treatment-induced increase of dopamine-mediated dopamine receptor D2 (DRD2) signaling inhibits choroidal neovascularization independently of MPTP-associated nigrostriatal pathway lesion. Analyzing a retrospective cohort of more than 200,000 patients with nAMD receiving anti-VEGF treatment from the French nationwide insurance database, we show that DRD2 agonist-treated PD patients have a significantly delayed age of onset of nAMD and reduced need for anti-VEGF therapies, similar to the effects of the l-DOPA treatment. While providing a mechanistic explanation for an intriguing epidemiological observation, our findings suggest that systemic DRD2 agonists might constitute an adjuvant therapy to delay and reduce the need for anti-VEGF therapy in patients with nAMD.

The AKT2/SIRT5/TFEB pathway as a potential therapeutic target in non-neovascular AMD.

Non-neovascular or dry age-related macular degeneration (AMD) is a multi-factorial disease with degeneration of the aging retinal-pigmented epithelium (RPE). Lysosomes play a crucial role in RPE health via phagocytosis and autophagy, which are regulated by transcription factor EB/E3 (TFEB/E3). Here, we find that increased AKT2 inhibits PGC-1α to downregulate SIRT5, which we identify as an AKT2 binding partner. Crosstalk between SIRT5 and AKT2 facilitates TFEB-dependent lysosomal function in the RPE. AKT2/SIRT5/TFEB pathway inhibition in the RPE induced lysosome/autophagy signaling abnormalities, disrupted mitochondrial function and induced release of debris contributing to drusen. Accordingly, AKT2 overexpression in the RPE caused a dry AMD-like phenotype in aging Akt2 KI mice, as evident from decline in retinal function. Importantly, we show that induced pluripotent stem cell-derived RPE encoding the major risk variant associated with AMD (complement factor H; CFH Y402H) express increased AKT2, impairing TFEB/TFE3-dependent lysosomal function. Collectively, these findings suggest that targeting the AKT2/SIRT5/TFEB pathway may be an effective therapy to delay the progression of dry AMD.

A journey through the world of vitreous.

Vitreous, one of the largest components of the human eye, mostly contains water. Despite decades of studying the vitreous structure, numerous unanswered questions still remain, fueling ongoing active research. We attempt to provide a comprehensive overview of the current understanding of the development, morphology, biochemical composition, and function of the vitreous. We emphasize the impact of the vitreous structure and composition on the distribution of drugs. Fast-developing imaging technologies, such as modern optical coherence tomography, unlocked multiple new approaches, offering the potential for in vivo study of the vitreous structure. They allowed to analyze in vivo a range of vitreous structures, such as posterior precortical vitreous pockets, Cloquet canal, channels that interconnect them, perivascular vitreous fissures, and cisterns. We provide an overview of such imaging techniques and their principles and of some challenges in visualizing vitreous structures. Finally, we explores the potential of combining the latest technologies and machine learning to enhance our understanding of vitreous structures.

JP4-039, a Mitochondria-Targeted Nitroxide, Mitigates the Effect of Apoptosis and Inflammatory Cell Migration in the Irradiated Mouse Retina.

We hypothesize that the injection of JP4-039, a mitochondria-targeted nitroxide, prior to irradiation of the mouse retina may decrease apoptosis and reduce neutrophil and macrophage migration into the retina. In our study, we aimed to examine the effects of JP4-039 in the mouse retina using fluorescent microscopy, a terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay, and flow cytometry. Forty-five mice and one eye per mouse were used. In Group 1, fluorescent microscopy was used to determine retinal uptake of 10 µL (0.004 mg/µL) of intravitreally injected BODIPY-labeled JP4-039 at 0, 15, and 60 min after injection. In Group 2, the TUNEL assay was performed to investigate the rate of apoptosis after irradiation in addition to JP4-039 injection, compared to controls. In Group 3, flow cytometry was used to determine the extent of inflammatory cell migration into the retina after irradiation in addition to JP4-039 injection, compared to controls. Maximal retinal uptake of JP4-039 was 15 min after intravitreal injection (p < 0.0001). JP4-039-treated eyes had lower levels of retinal apoptosis (35.8 ± 2.5%) than irradiated controls (49.0 ± 2.7%; p = 0.0066) and demonstrated reduced migration of N1 cells (30.7 ± 11.7% vs. 77.7 ± 5.3% controls; p = 0.004) and M1 cells (76.6 ± 4.2 vs. 88.1 ± 3.7% controls, p = 0.04). Pretreatment with intravitreally injected JP4-039 reduced apoptosis and inflammatory cell migration in the irradiated mouse retina, marking the first confirmed effect of this molecule in retinal tissue. Further studies may allow for safety profiling and potential use for patients with radiation retinopathy.

Phase 1/2 AAV5-hRKp.RPGR (Botaretigene Sparoparvovec) Gene Therapy: Safety and Efficacy in RPGR-Associated X-Linked Retinitis Pigmentosa.

PURPOSE: To assess the safety and efficacy of AAV5-hRKp.RPGR in participants with retinitis pigmentosa GTPase regulator (RPGR)-associated X-linked retinitis pigmentosa (XLRP). DESIGN: Open-label, phase 1/2 dose escalation/expansion study (ClinicalTrials.gov Identifier: NCT03252847). METHODS: Males (≥5 years old) with XLRP-RPGR were evaluated. In the dose escalation phase, subretinal AAV5-hRKp.RPGR (low: 1.0 × 1011 vg/ml; intermediate: 2.0 × 1011 vg/ml; high: 4.0 × 1011 vg/ml) was administered to the poorer-seeing eye (n = 10). Dose confirmation (intermediate dose) was carried out in 3 pediatric participants. In the dose expansion phase, 36 participants were randomized 1:1:1 to immediate (low or intermediate dose) or deferred (control) treatment. The primary outcome was safety. Secondary efficacy outcomes included static perimetry, microperimetry, vision-guided mobility, best corrected visual acuity, and contrast sensitivity. Safety and efficacy outcomes were assessed for 52 weeks for immediate treatment participants and 26 weeks for control participants. RESULTS: AAV5-hRKp.RPGR was safe and well tolerated, with no reported dose-limiting events. Most adverse events (AEs) were transient and related to the surgical procedure, resolving without intervention. Two serious AEs were reported with immediate treatment (retinal detachment, uveitis). A third serious AE (increased intraocular pressure) was reported outside the reporting period. All ocular inflammation-related AEs responded to corticosteroids. Treatment with AAV5-hRKp.RPGR resulted in improvements in retinal sensitivity and functional vision compared with the deferred group at Week 26; similar trends were observed at Week 52. CONCLUSIONS: AAV5-hRKp.RPGR demonstrated an anticipated and manageable AE profile through 52 weeks. Safety and efficacy findings support investigation in a phase 3 trial.

RDH5 and RLBP1-Associated Inherited Retinal Diseases: Refining the Spectrum of Stationary and Progressive Phenotypes.

PURPOSE: To investigate the clinical, functional, and imaging characteristics in patients affected by inherited retinal diseases associated with RDH5 and RLBP1 gene variants, and to report novel genotype-phenotype correlations. DESIGN: Retrospective single-center cohort study. METHODS: Twenty-two patients with molecularly confirmed RLBP1-associated retinopathy and 5 with RDH5-associated retinopathy. Medical records were reviewed to obtain data on family history and ophthalmologic examinations, including retinal imaging and full-field electroretinography (ffERG). Genotype was determined by targeted next-generation sequencing followed by confirmation and familial segregation by Sanger sequencing. RESULTS: The median (interquartile ranges) age at baseline for the RDH5 and RLBP1 cohort was 44.6 (38.2-67.9) years and 36.9 (23.1-45.2) years, respectively. Macular atrophy (MA) was found in approximately 80% of eyes from both cohorts. The RLBP1 genotype was associated with a lower macular volume by 0.28 mm3 (95% CI, -0.46 to -0.11; P = .005) compared to the RDH5 genotype. In both genotypic cohorts, we found a significant annual rate of macular volume loss, estimated at -0.007 mm3/y (95% CI, -0.012 to -0.001; P = .02), without any significant difference between the two genotypes. Three unrelated patients homozygous for the c.361C>T p.(Arg121Trp) RLBP1 variant showed minimal impairment of both the rod and cone systems function on ffERG and absence of MA. CONCLUSIONS: Progressive MA in addition to congenital night blindness can be identified in adult patients with RDH5-associated retinopathy. Vice versa, hypomorphic RLBP1 variants may cause milder retinal phenotypes rather than the typical severe rod-cone dystrophy with MA. These findings could prove beneficial to improve the prognostication of patients and help in designing future interventional trials.

Deep learning based characterization of human organoids using optical coherence tomography.

Organoids, derived from human induced pluripotent stem cells (hiPSCs), are intricate three-dimensional in vitro structures that mimic many key aspects of the complex morphology and functions of in vivo organs such as the retina and heart. Traditional histological methods, while crucial, often fall short in analyzing these dynamic structures due to their inherently static and destructive nature. In this study, we leveraged the capabilities of optical coherence tomography (OCT) for rapid, non-invasive imaging of both retinal, cerebral, and cardiac organoids. Complementing this, we developed a sophisticated deep learning approach to automatically segment the organoid tissues and their internal structures, such as hollows and chambers. Utilizing this advanced imaging and analysis platform, we quantitatively assessed critical parameters, including size, area, volume, and cardiac beating, offering a comprehensive live characterization and classification of the organoids. These findings provide profound insights into the differentiation and developmental processes of organoids, positioning quantitative OCT imaging as a potentially transformative tool for future organoid research.

Label-Free Imaging of Inflammation at the Level of Single Cells in the Living Human Eye.

Purpose: Putative microglia were recently detected using adaptive optics ophthalmoscopy in healthy eyes. Here we evaluate the use of nonconfocal adaptive optics scanning light ophthalmoscopy (AOSLO) for quantifying the morphology and motility of presumed microglia and other immune cells in eyes with retinal inflammation from uveitis and healthy eyes. Design: Observational exploratory study. Participants: Twelve participants were imaged, including 8 healthy participants and 4 posterior uveitis patients recruited from the clinic of 1 of the authors (M.H.E.). Methods: The Pittsburgh AOSLO imaging system was used with a custom-designed 7-fiber optical fiber bundle for simultaneous confocal and nonconfocal multioffset detection. The inner retina was imaged at several locations at multiple timepoints in healthy participants and uveitis patients to generate time-lapse images. Main Outcome Measures: Microglia and macrophages were manually segmented from nonconfocal AOSLO images, and their morphological characteristics quantified (including soma size, diameter, and circularity). Cell soma motion was quantified across time for periods of up to 30 minutes and their speeds were calculated by measuring their displacement over time. Results: A spectrum of cell morphologies was detected in healthy eyes from circular amoeboid cells to elongated cells with visible processes, resembling activated and ramified microglia, respectively. Average soma diameter was 16.1 ± 0.9 µm. Cell movement was slow in healthy eyes (0.02 µm/sec on average), but macrophage-like cells moved rapidly in some uveitis patients (up to 3 µm/sec). In an eye with infectious uveitis, many macrophage-like cells were detected; during treatment their quantity and motility decreased as vision improved. Conclusions: In vivo adaptive optics ophthalmoscopy offers promise as a potentially powerful tool for detecting and monitoring inflammation and response to treatment at a cellular level in the living eye. Financial Disclosures: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Ophthalmological research in Germany: suggestions by an international expert panel.

PURPOSE: To evaluate the research performance in ophthalmology in Germany based on the findings of the recent research map of the German Ophthalmological Society (DOG) and to suggest strategies for future improvements on a national level both to DOG as well as to politics. The focus is on preclinical and translational clinical research. METHODS: International expert panel evaluation and discussion organized by the Task Force Research of the German Ophthalmological Society (DOG). RESULTS: The international view on the German ophthalmological research landscape was generally positive. The value for money relationship was judged as very good. As Germany is facing an aging society and vision impairment will create an ever-increasing socioeconomic burden, the reviewers suggested several lines of future activities: an increased activity of securing intellectual property, more lay audience lobbying, intensified collaboration and critical mass building between "lighthouses" of ophthalmic research in Germany, as well as the establishment of a German national eye institute equivalent. CONCLUSION: The ophthalmological research performance in Germany was rated to be very good by an international expert panel. Nonetheless significant improvements were requested in the fields of translation (clinical trials, IP), synergy between specialized institutions and governmental funding for a German center for eye research.

[Ophthalmological research in Germany: evaluation by an international expert panel]. / Ophthalmologische Forschung in Deutschland: Evaluation durch ein internationales Expertengremium.

PURPOSE: To evaluate the research performance in ophthalmology in Germany based on the findings of the recent research map of the German Ophthalmological Society ( DOG) and to suggest strategies for future improvements on a national level both to DOG as well as to politics. The focus is on preclinical and translational clinical research. METHODS: International expert panel evaluation and discussion organized by the Task Force Research of the German Ophthalmological Society (DOG). RESULTS: The international view on the German ophthalmological research landscape was generally positive. The value for money relationship was judged as very good. As Germany is facing an aging society and vision impairment will create an ever-increasing socioeconomic burden, the reviewers suggested several lines of future activities: an increased activity of securing intellectual property, more lay audience lobbying, intensified collaboration and critical mass building between "lighthouses" of ophthalmic research in Germany, as well as the establishment of a German national eye institute equivalent. CONCLUSION: The ophthalmological research performance in Germany was rated to be very good by an international expert panel. Nonetheless significant improvements were requested in the fields of translation (clinical trials, IP), synergy between specialized institutions and governmental funding for a German center for eye research.

Oral 8-aminoguanine against age-related retinal degeneration.

Visual decline in the elderly is often attributed to retinal aging, which predisposes the tissue to pathologies such as age-related macular degeneration. Currently, effective oral pharmacological interventions for retinal degeneration are limited. We present a novel oral intervention, 8-aminoguanine (8-AG), targeting age-related retinal degeneration, utilizing the aged Fischer 344 rat model. A low-dose 8-AG regimen (5 mg/kg body weight) via drinking water, beginning at 22 months for 8 weeks, demonstrated significant retinal preservation. This was evidenced by increased retinal thickness, improved photoreceptor integrity, and enhanced electroretinogram responses. 8-AG effectively reduced apoptosis, oxidative damage, and microglial/macrophage activation associated with aging retinae. Age-induced alterations in the retinal purine metabolome, characterized by elevated levels of inosine, hypoxanthine, and xanthine, were partially mitigated by 8-AG. Transcriptomics highlighted 8-AG's anti-inflammatory effects on innate and adaptive immune responses. Extended treatment to 17 weeks further amplified the retinal protective effects. Moreover, 8-AG showed temporary protective effects in the RhoP23H/+ mouse model of retinitis pigmentosa, reducing active microglia/macrophages. Our study positions 8-AG as a promising oral agent against retinal aging. Coupled with previous findings in diverse disease models, 8-AG emerges as a promising anti-aging compound with the capability to reverse common aging hallmarks.