Gene Therapies in Clinical Development to Treat Retinal Disorders.

Gene therapies have emerged as promising treatments in clinical development for various retinal disorders, offering hope to patients with inherited degenerative eye conditions. Several gene therapies have already shown remarkable success in clinical trials, with significant improvements observed in visual acuity and the preservation of retinal function. A multitude of gene therapies have now been delivered safely in human clinical trials for a wide range of inherited retinal disorders but there are some gaps in the reported trial data. Some of the most exciting treatment options are not under peer review and information is only available in press release form. Whilst many trials appear to have delivered good outcomes of safety, others have failed to meet primary endpoints and therefore not proceeded to phase III. Despite this, such trials have enabled researchers to learn how best to assess and monitor patient outcomes, which will guide future trials to greater success. In this review, we consider recent and ongoing clinical trials for a variety of potential retinal gene therapy treatments and discuss the positive and negative issues related to these trials. We discuss the treatment potential following clinical trials as well as the potential risks of some treatments under investigation. As these therapies continue to advance through rigorous testing and regulatory approval processes, they hold the potential to revolutionise the landscape of retinal disorder treatments, providing renewed vision and enhancing the quality of life for countless individuals worldwide.

Outcome measures in childhood glaucoma: a systematic review of randomized controlled trials.

PURPOSE: To synthesize the outcome measures used by randomized controlled trials (RCTs) for childhood glaucoma. METHODS: MEDLINE, EMBASE, and Scopus were searched from inception to February 17, 2023. Randomized controlled trials and observational studies related to childhood glaucoma were included. Primary and secondary outcomes were extracted and the data was used to generate a literature review. RESULTS: This review identified 42 unique reports pertaining to childhood glaucomas. Most of the studies originated from Egypt, India, and the USA. Intraocular pressure (IOP) outcomes were the most frequent outcomes studied, followed by clinical outcomes and safety outcomes. Clinical outcomes were the most common secondary outcomes studied, followed by IOP outcomes and safety outcomes. CONCLUSIONS: This systematic review found heterogenous outcomes with IOP outcomes as the most studied primary outcome. As the remaining outcomes were not consistently utilized, this review highlights the need for a consensus on studies of pediatric glaucoma.

Potential CRISPR Base Editing Therapeutic Options in a Sorsby Fundus Dystrophy Patient.

TIMP3 mutations are associated with early-onset macular choroidal neovascularisation for which no treatment currently exists. CRISPR base editing, with its ability to irreversibly correct point mutations by chemical modification of nucleobases at DNA level, may be a therapeutic option. We report a bioinformatic analysis of potential therapeutic options in a patient presenting with Sorsby fundus dystrophy. Genetic testing in a 35-year-old gentleman with bilateral macular choroidal neovascularisation revealed the patient to be heterozygous for a TIMP3 variant c.610A>T, p.(Ser204Cys). Using a glycosylase base editor (GBE), another DNA-edit could be introduced that would revert the variant back to wild-type on amino acid level. Alternatively, the mutated residue could be changed to another amino acid that would be better tolerated, and for that, an available 'NG'-PAM site was found to be available for the SpCas9-based adenine base editor (ABE) that would introduce p.(Ser204Arg). In silico analyses predicted this variant to be non-pathogenic; however, a bystander edit, p.Ile205Thr, would be introduced. This case report highlights the importance of considering genetic testing in young patients with choroidal neovascularisation, particularly within the context of a strong family history of presumed wet age-related macular degeneration, and describes potential therapeutic options.

Comparison of outcomes of four different treatment modalities for diabetic vitreous haemorrhage.

We compared outcomes of four different management modalities for diabetic VH. Patients with diabetic VH were identified in this retrospective study undertaken at King Khaled Eye Specialist Hospital, Riyadh, Saudi Arabia. Eyes were grouped based on the treatment received: control (observation only), intravitreal bevacizumab (IVB) injection(s), pars plana vitrectomy (PPV), and preoperative single IVB injection before PPV. Best-corrected visual acuity (BCVA) and status of VH were noted at baseline and the last follow up (Minimum: 6 months, maximum: 29 months). The proportion of eyes with Snellen BCVA improvement by two lines or more and VH clearance at the last follow up were compared between groups. The four groups - Control, IVB, PPV, and IVB-before-PPV had 23, 29, 17, and 20 eyes, respectively. The proportion of eyes gaining ≥2 lines was substantially higher in the IVB-before-PPV and PPV groups (90% and 77%, respectively) compared with IVB and observation groups (41% and 22%, respectively). Surgical treatment was associated with a 2.38 times higher likelihood of gaining ≥2 lines than the non-surgical one (incidence ratio: 2.38, 95% CI 1.19, 4.78 P = 0.015) after adjusting for age, hyperglycemia and BCVA at presentation. Less invasive treatment such as IVB injections did not result in the same amount of improvement in vision as did PPV. Prospective randomized studies are needed to better define the role of IVB injections in the management of diabetic VH.