ABSTRACT
Retinitis pigmentosa (RP) is a heterogeneous group of hereditary diseases characterized by progressive degeneration of retinal photoreceptors leading to progressive visual decline. It is the most common type of inherited retinal dystrophy and has a high burden on both patients and society. This condition causes gradual loss of vision, with its typical manifestations including nyctalopia, concentric visual field loss, and ultimately bilateral central vision loss. It is one of the leading causes of visual disability and blindness in people under 60 years old and affects over 1.5 million people worldwide. There is currently no curative treatment for people with RP, and only a small group of patients with confirmed RPE65 mutations are eligible to receive the only gene therapy on the market: voretigene neparvovec. The current therapeutic armamentarium is limited to retinoids, vitamin A supplements, protection from sunlight, visual aids, and medical and surgical interventions to treat ophthalmic comorbidities, which only aim to slow down the progression of the disease. Considering such a limited therapeutic landscape, there is an urgent need for developing new and individualized therapeutic modalities targeting retinal degeneration. Although the heterogeneity of gene mutations involved in RP makes its target treatment development difficult, recent fundamental studies showed promising progress in elucidation of the photoreceptor degeneration mechanism. The discovery of novel molecule therapeutics that can selectively target specific receptors or specific pathways will serve as a solid foundation for advanced drug development. This article is a review of recent progress in novel treatment of RP focusing on preclinical stage fundamental research on molecular targets, which will serve as a starting point for advanced drug development. We will review the alterations in the molecular pathways involved in the development of RP, mainly those regarding endoplasmic reticulum (ER) stress and apoptotic pathways, maintenance of the redox balance, and genomic stability. We will then discuss the therapeutic approaches under development, such as gene and cell therapy, as well as the recent literature identifying novel potential drug targets for RP.
ABSTRACT
Purpose: To evaluate the effects of autologous platelet-rich plasma (PRP) drops for evaporative dry eye (EDE) disease from meibomian gland dysfunction (MGD). Methods: This is a retrospective, consecutive case series of 20 eyes of 10 patients with EDE from MGD treated with PRP drops from November 2020 to November 2021 at a single outpatient clinic in Ontario, Canada. PRP drops were prepared from whole blood using a two-step centrifugation method. Patients were instructed to instill these drops six times daily for 4 weeks. The Canadian Dry Eye Assessment (CDEA) questionnaire score, patient subjective assessment (PSA) score, first and average non-invasive break-up times (f/a NIBUT), tear meniscus height (TMH), bulbar redness (BR), and meibograph grade (MG) were measured before and after the treatment course. Results: Significant improvements in dry eye symptoms and tear film parameters were observed. Dry eye symptoms significantly improved as per the CDEA (mean difference (MD) = -5.45, 95% confidence interval (CI) = [-7.9, -3.1], p<0.001) and PSA (MD = -2.6, 95% CI = [-3.9, -1.2], p<0.001). There were significant improvements in tear film parameters including fNIBUT (MD = 3.85s, 95% CI = [1.2, 6.8], p=0.006), aNIBUT (MD = -6.81s, 95% CI = [5.7, 11.1], p<0.001) and TMH (MD = 0.08, 95% CI = [0.003, 0.2], p=0.045). There was an improvement in conjunctival injection as measured by BR (MD = -0.36, 95% CI = [-0.4, -0.15], p=0.373). Five eyes experienced a one-grade improvement in MG (p=0.453), and none experienced worsening in MG with treatment. No temporary or permanent adverse effects were noted. Conclusion: Four weeks of PRP therapy resulted in significant functional improvements in dry eye symptoms and tear film quality and quantity. Improvements in conjunctival injection and microstructural improvements in meibomian glands were also observed in some eyes. Overall, PRP is a promising treatment option for patients with EDE from MGD refractory to conventional treatments.
ABSTRACT
BACKGROUND: BroadBand light intense pulsed light (BBL-IPL) therapy has shown to reduce hordeolum and blepharitis frequency. This study aims to evaluate the efficacy and safety of BBL-IPL therapy in patients with dry eye disease (DED) from meibomian gland dysfunction (MGD). METHODS: This is a retrospective, consecutive case series of 48 patients with DED from MGD who underwent BBL-IPL therapy from October 2016 to January 2019 at a single, outpatient clinic in Ontario, Canada. Clinical outcomes included first and average non-invasive keratograph tear break-up times (NIKBUT), bulbar redness (BR) scores, tear meniscus heights (TMH), visual acuity (VA) and meibograph grades. Patient-reported outcomes included the Canadian dry eye assessment (CDEA) questionnaire and patient subjective assessment (PSA) scores. Outcomes were measured at baseline and after completion of 4 monthly BBL-IPL sessions. RESULTS: The mean severity of dry eye symptoms as measured by the CDEA and PSA decreased significantly from 19.78 ± 9.62 to 12.08 ± 7.40 (p<0.001) and from 7.65 ± 1.74 to 4.77 ± 2.03 (p<0.001), respectively. Twenty-five percent of patients reported no dry eye symptoms after treatment. The meibograph grade improved significantly in both eyes (p<0.001). Approximately 71.0% and 80.1% of patients had an improved meibograph grade in the right and left eye, respectively. Near-significant improvements were observed for BR scores and VA. There was also a trend towards improved first/average NIKBUT and TMH scores. No adverse events were noted. CONCLUSION: BBL-IPL appears to be an effective and safe treatment modality in improving dry eye symptoms and meibomian gland function in patients with DED from MGD.
