J. Clin. Transl. Ophthalmol., Volume 2, Issue 3 (September 2024) – 4 articles

Background: Pre-clinical studies related to the use of rapamycin (Sirolimus^®), a mammalian target of rapamycin (mTOR) inhibitors, for age-related macular degeneration (AMD) have shown improved therapeutic outcomes. However, knowledge of its dose–effect relationship in humans with AMD has been limited and requires further investigation. Objective: The aim of this study is to assess the safety and efficacy of Sirolimus^® for treatment of AMD in humans and determine the dose range for its application in the eye. Methods: A systematic literature review was conducted following the PRISMA guidelines. The MEDLINE, Embase, CINAHL, Scopus and Cochrane Central Registry of Controlled Trials databases were searched for original clinical studies examining the effects of Sirolimus^® on outcomes linked to AMD in humans. This review has been registered in the PROSPERO database. Results: Only four studies were found to satisfy the inclusion and exclusion criteria and were analyzed in this systematic review in a narrative way. The dose range of rapamycin in the limited number of studies appears to be toxic to the retina. Conclusion: Future studies should focus on establishing the optimal low-dose range of Sirolimus^® that effectively induces autophagy without causing retinal toxicity, as current data indicate a potential therapeutic window that remains underexplored. Specifically, longitudinal, controlled studies with larger, heterogeneous patient populations are necessary to determine the precise dosing that balances efficacy and safety in treating AMD. Full article

(1) Background: It is estimated that 10% of dry eye disease (DED) occurs in patients with Sjogren’s syndrome (SS-DED) and represents a challenge when it comes to treatment. Both innate and adaptive immunity participate in the pathogenesis of SS-DED. Previous studies suggest that Th1 and Th17 cell immune responses are the main actors associated with the pathogenesis of this disease. Ocular surface mucins play a fundamental role in ocular surface homeostasis. In particular, the main transmembrane mucins, MUC1, MUC4 and MUC16, are dysregulated in DED and could be involved in the activation of pro-inflammatory cytokines at the ocular interface. Thus, the objective of this work was to analyze mucin and cytokine expression in ocular surface (OS) damage and correlate it with clinical symptoms.; (2) Methods: 18 patients with SS-DED and 15 healthy controls were included in the study. Samples of conjunctival cells were obtained through cytology impression. RNA was extracted from the collected samples and used to determine the expression of MUC1, 4 and 16 by qRT-PCR. Pro-inflammatory cytokines associated with DED pathogenesis (IL17 and IL-22) were also evaluated. The results were contrasted with the clinical findings on examination of the patients. (3) Results: We observed a significant increase in the expression of MUC1 and MUC4 in patients with SS-DED. MUC4 significantly correlated with both lower production and stability of the tear film, as well as greater superficial keratopathy. On the other hand, MUC1 and MUC16 were positively correlated with the presence of more severe DED symptoms. However, we could not reproduce an increase in IL-17 and IL-22 in DED patients as previously reported; (4) Conclusions: This work constitutes an approach to understanding how the gene expression of transmembrane mucins associates with SS-DED symptoms and clinical signs. Full article

With increasing space exploration, there is a rising need to evaluate the impact of spaceflight on astronauts’ health, including the effects of space-associated hazards such as microgravity. Astronauts’ reports of experienced symptoms upon spaceflight include a notable prevalence of dry eye disease (DED). Hence, there is a pressing need to understand the pathogenesis and mechanism behind space-associated DED onset, which will subsequently guide the development of necessary therapies to reduce dry eye symptoms among astronauts. One critical effect of spaceflight includes alterations to the gut microbiome. On Earth, the prior literature has established the presence of an ocular surface–gut axis and the potential role of gut dysbiosis in DED onset. Meanwhile, the literature about astronauts’ health underscores the presence of space-associated gut microbiome composition alterations and the presence of DED separately. Therefore, in this opinion article, we review and present the current literature regarding the ocular surface–gut axis on Earth and regarding potential translations to spaceflight. We present the view that, based on the existing literature, the ocular surface–gut axis may be a critical mechanism for the pathogenesis of DED in space, and this axis needs to be further explored in the context of identifying ways to reduce astronauts’ experiences of DED during spaceflight. Full article

Hereditary optic neuropathies (HONs) are a class of genetic disorders that may lead to vision loss due to either acute or progressive injury to the optic nerve. Although HONs may commonly manifest as isolated optic atrophy, these disorders can also have a variety of characteristic clinical features and time courses that may narrow the differential diagnosis. While the two most prevalent HONs are Leber Hereditary Optic Neuropathy (LHON) and Dominant Optic Atrophy (DOA), the phenotypic spectrum of these conditions, as well as genetic landscape of less common optic neuropathies, have been better characterized through advances in molecular diagnostic testing. Treatment targeting various pathogenic mechanisms has been investigated, although studies of clinical applicability remain nascent. Present management largely remains supportive. In this review, we discuss the clinical features, molecular diagnosis, current treatment, and future directions for HONs. Full article