The cornea, with its delicate structure, is vulnerable to damage from physical, chemical, and genetic factors. Corneal transplantation, including penetrating and lamellar keratoplasties, can restore the functions of the cornea in cases of severe damage. However, the process of corneal transplantation presents considerable obstacles, including a shortage of available donors, the risk of severe graft rejection, and potentially life-threatening complications. Over the past few decades, mesenchymal stem cell (MSC) therapy has become a novel alternative approach to corneal regeneration. Numerous studies have demonstrated the potential of MSCs to differentiate into different corneal cell types, such as keratocytes, epithelial cells, and endothelial cells. MSCs are considered a suitable candidate for corneal regeneration because of their promising therapeutic perspective and beneficial properties. MSCs compromise unique immunomodulation, anti-angiogenesis, and anti-inflammatory properties and secrete various growth factors, thus promoting corneal reconstruction. These effects in corneal engineering are mediated by MSCs differentiating into different lineages and paracrine action via exosomes. Early studies have proven the roles of MSC-derived exosomes in corneal regeneration by reducing inflammation, inhibiting neovascularization, and angiogenesis, and by promoting cell proliferation. This review highlights the contribution of MSCs and MSC-derived exosomes, their current usage status to overcome corneal disease, and their potential to restore different corneal layers as novel therapeutic agents. It also discusses feasible future possibilities, applications, challenges, and opportunities for future research in this field.

Dry eye disease (DED) is an emerging health issue affecting millions of individuals annually. Ocular surface disorders, such as DED, are characterized by inflammation triggered by various factors. This condition can lead to tear deficiencies, resulting in the desiccation of the ocular surface, corneal ulceration/perforation, increased susceptibility to infections, and a higher risk of severe visual impairment and blindness. Currently, the clinical management of DED primarily relies on supportive and palliative measures, including the frequent and lifelong use of different lubricating agents. While some advancements like punctal plugs, non-steroidal anti-inflammatory drugs, and salivary gland autografts have been attempted, they have shown limited effectiveness. Recently, there have been promising developments in the treatment of DED, including biomaterials such as nano-systems, hydrogels, and contact lenses for drug delivery, cell-based therapies, biological approaches, and tissue-based regenerative therapy. This article specifically explores the different strategies reported so far for treating DED. The aim is to discuss their potential as long-term cures for DED while also considering the factors that limit their feasibility and effectiveness. These advancements offer hope for more effective and sustainable treatment options in the future.

Dry eye disease (DED) is a growing health concern that impacts millions of individuals every year, and is associated with corneal injury, excessive oxidative stress and inflammation. Current therapeutic strategies, including artificial tears and anti-inflammatory agents, are unable to achieve a permanent clinical cure due to their temporary nature or adverse side effects. Therefore, here, we investigated the effectiveness of the topical administration of programmed death-ligand 1 (PD-L1) in the mouse model of DED. The model was generated in C57BL/6 mice by excising the extra orbital lacrimal gland and causing desiccation stress with scopolamine injections. Subsequently, either phosphate-buffered saline (3 µL/eye) or PD-L1 (0.5 µg/mL) was topically administered for 10 days. Tear volume was evaluated with phenol red thread, and corneal fluorescein staining was observed to quantify the corneal epithelial defect. Corneas were collected for histological analysis, and the expression levels of inflammatory signaling proteins such as CD4, CD3e, IL-17, IL-1β, pIkB-α, pNF-kB and pERK1/2 were assessed through immunofluorescence and Western blot techniques. Our results demonstrate that desiccating stress-induced corneal epithelial defect and tear secretion were significantly improved by topical PD-L1 and could reduce corneal CD4+ T cell infiltration, inflammation and apoptosis in a DED mouse model by downregulating IL-17 production and ERK1/2-NFkB pathways.

Objectives: To compare the long-term efficacy and safety of intense pulsed light (IPL) treatments using a 590-nm and an acne filter. Methods: In this prospective, randomized, paired-eye trial study, 30 patients with moderate and severe meibomian gland dysfunction (MGD) were followed up for at least one month after their last treatment. Group A received IPL treatment with an acne filter, a type of notch filter that blocks wavelengths between 600 and 800 nm, allowing IPL to emit wavelengths between 400–600 nm and 800–1200 nm. Group B received treatment with a 590 nm filter, a type of cut-off filter that blocks wavelengths below 590 nm. Clinical parameters, including tear osmolarity, matrix metalloproteinase (MMP)-9 expression, tear break-up time, ocular surface staining scores, Schirmer’s test I, lid margin telangiectasia scores, MG expressibility/secretion scores, and Ocular Surface Disease Index scores, were measured at baseline, 1, 6, and 12 months after their last treatment. Results: In the linear mixed model, significant time effects on all clinical parameters, except for MMP-9 grades and Schirmer’s test I results, were observed within each group. However, interactions between time points (baseline, 6 months, 12 months) and groups (Group A, B) were not significant. The generalized estimating equation model showed no significant interaction between time points and groups for MMP-9 positivity; however, a significant time effect on MMP-9 positivity was observed in Group A, with a decrease at 12 months after their last treatment when compared to baseline and 6 months. Conclusions: The IPL treatment modality for moderate to severe MGD demonstrated a significant therapeutic effect for one year under strictly controlled self-administration of other treatments. IPL treatment using acne filter is a promising treatment option for reducing MMP-9 positivity in MGD patients.

Objectives: To investigate the clinical characteristics of patients with meibomian gland dysfunction (MGD) who are refractory to additional intense pulsed light (IPL) treatment. Materials and Methods: This retrospective study included 66 eyes of 66 patients with moderate-to-severe MGD who had previously undergone four sessions of IPL treatment with a 590 nm filter at another clinic and, received an additional four sessions of IPL treatment with a vascular filter. Patients’ subjective assessments before and after the additional IPL treatments were scored on a scale from 0 to 4, where 0 = moderate improvement, 1 = mild improvement, 2 = no change, and 3 = aggravated MGD. Patients who scored 0 or 1 were classified as Group 1 (Responsive group), while those who scored 2 or 3 were classified as Group 2 (Refractory group). Results: Among the 66 eyes from 66 patients, Group 1 comprised 32 eyes and Group 2 comprised 34 eyes. Patients in the refractory group, who did not respond to additional IPL treatment, exhibited poor ocular staining scores before additional IPL treatment. The responsive group showed better treatment responses with regard to the Oxford and Sjögren’s International Clinical Collaborative Alliance (SICCA) staining scores (all p < 0.001), upper and lower lid meibum quality and meibum consistency, and meibomian gland grade (all p < 0.001). Changes in the Oxford staining score (p = 0.032), SICCA staining score (p = 0.003), meibum quality (p < 0.001), meibum consistency (p < 0.001), and meibomian gland grade (p < 0.001), before and after the additional treatment, were significantly greater in Group 1 than in Group 2. Conclusions: Additional IPL treatment with a vascular filter may provide further clinical benefits in selected patients with moderate-to-severe MGD who have previously undergone IPL therapy. Poor baseline ocular surface staining was associated with a lower likelihood of treatment response and may help identify patients who are less likely to benefit from additional IPL treatment.