Gene-Based Therapeutics for Acquired Retinal Disease: Opportunities and Progress.

Acquired retinal diseases such as age-related macular degeneration and diabetic retinopathy rank among the leading causes of blindness and visual loss worldwide. Effective treatments for these conditions are available, but often have a high treatment burden, and poor compliance can lead to disappointing real-world outcomes. Development of new treatment strategies that provide more durable treatment effects could help to address some of these unmet needs. Gene-based therapeutics, pioneered for the treatment of monogenic inherited retinal disease, are being actively investigated as new treatments for acquired retinal disease. There are significant advantages to the application of gene-based therapeutics in acquired retinal disease, including the presence of established therapeutic targets and common pathophysiologic pathways between diseases, the lack of genotype-specificity required, and the larger potential treatment population per therapy. Different gene-based therapeutic strategies have been attempted, including gene augmentation therapy to induce in vivo expression of therapeutic molecules, and gene editing to knock down genes encoding specific mediators in disease pathways. We highlight the opportunities and unmet clinical needs in acquired retinal disease, review the progress made thus far with current therapeutic strategies and surgical delivery techniques, and discuss limitations and future directions in the field.

Intravitreal Injection with a Conjunctival Injection Device: A Single-Center Experience.

Purpose: To evaluate the clinical performance of the intravitreal injection assistant device (InVitria) compared with the conventional freehand technique for delivering intravitreal injections. Methods: Seventy patients were randomized to receive intravitreal injections via the conventional freehand technique while 70 received injections using the InVitria. Half of all procedures in each group were performed by junior surgeons, while the rest were performed by senior surgeons. Results: Mean injections times were 90.0 ± 23.3 seconds and 64.9 ± 26.8 seconds for conventional versus InVitria (P < 0.001). Mean injection times with the conventional technique were 85.5 ± 23.0 seconds vs. 94.2 ± 23.0 seconds for senior versus junior surgeons (P = 0.120). Mean injection times with the InVitria were 56.1 ± 26.1 seconds vs. 66.3 ± 26.9 seconds (P = 0.211) for senior versus junior surgeons. There were no significant differences in pain scores regardless of technique (conventional versus In Vitria: 2.03 ± 1.73 vs. 2.13 ± 2.20, P = 0.770). Conclusions: In our experience, the InVitria is a comparable alternative to the conventional freehand technique of delivering intravitreal injections, with the potential for faster injection times and without compromising on patient comfort. Translational Relevance: The study provides evidence to suggest that the InVitria may be deployed effectively in clinical practice.

Correction: Design, implementation, and evaluation of a nurse-led intravitreal injection programme for retinal diseases in Singapore.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Design, implementation, and evaluation of a nurse-led intravitreal injection programme for retinal diseases in Singapore.

BACKGROUND: To describe the design, implementation, and evaluation of a nurse-led intravitreal injection (NL-IVT) programme in a Singapore tertiary eye hospital. METHODS: Patients requiring anti-vascular endothelial growth factor (VEGF) IVT were recruited. Implementation and evaluation were done in the Singapore National Eye Centre, a tertiary centre. To assess safety, nurse injectors recorded details of procedures performed and complications for an 8-month period from February 2019. To evaluate patient experience, we used a modified patient questionnaire and recorded both patients' waiting time and IVT procedure duration. A retrospective audit of IVTs before and after the introduction of NL-IVT was performed from January 2017 to September 2019. Cost difference between NL-IVT and standard doctor-led (DL) IVT was evaluated. RESULTS: A total of 8599 NL-IVTs were performed. No cases of severe complication were detected in the follow-up. A total of 135 patients who received NL-IVT and DL-IVT were surveyed. General satisfaction, interpersonal manner, financial aspect, time spent with injector, and staff competence were higher in NL-IVTs than in DL-IVTs (p < 0.05). There were no differences in terms of technical quality and communication. For 934 patients, waiting time was significantly shorter in NL-IVT (3.6 ± 10.3 min) compared with DL-IVTs (35.3 ± 32.3 min); on average, 19.7 min were saved through NL-IVT (p < 0.01). The cost difference per IVT between NL-IVT and DL-IVT is estimated at 286 SGD (163 GBP). CONCLUSION: With a well-designed training programme, NL-IVT is a safe, acceptable, and cost savings procedure. With increasing demand for IVT, NL-IVT provides an alternative model of care for healthcare systems globally.

Correlation of axial length and myopic macular degeneration to levels of molecular factors in the aqueous.

To elucidate the molecular processes associated with the development of myopic macular degeneration (MMD), we measured the intraocular concentrations of molecular factors in emmetropic and myopic eyes. This is a retrospective clinic-based case-control study that included eyes undergoing routine cataract surgery whereby aqueous humour samples were obtained. We measured the concentrations of pigment epithelium derived factor(PEDF), matrix metalloproteinase 2(MMP-2), tissue inhibitor of metalloproteinase(TIMP-2), vascular endothelial growth factor isoform A(VEGF-A), interleukin 8(IL-8), interleukin 6(IL-6), C-reactive protein(CRP), angiopoietin 2(Ang2), and amphiregulin. 38 eyes (axial length (AL): 22.4-32.4 mm), including 12 highly myopic (HM) eyes (AL ≥ 26.5 mm) without MMD and 12 HM eyes with MMD but without neovascularization were included. Eyes with MMD were found to have significantly lower VEGF-A levels (p = 0.007) and higher MMP-2 levels (p = 0.02) than control eyes after adjusting for age and gender. MMP-2 levels correlated positively (r = 0.58, p = 0.002), while VEGF-A levels correlated negatively with longer axial length (r = -0.75, p < 0.001). Both the concentrations of VEGF-A (P = 0.25) and MMP-2 (P = 0.69) were not significantly associated with MMD after adjusting for AL. These findings suggest that the predominant mechanism underlying the development of non-neovascular MMD may be axial elongation, driven in part by MMP-2 related mechanisms.