Table 2.
Summary of emerging treatment options for SSDE.
| Clinical Trials | ||
|---|---|---|
| Biologic Immunomodulators | Immunomodulation through innate and adaptive immune system. Rituxumab: anti-CD20 antibody [42] Belimumab: anti-BAFF antibody [43] Epratuzumab: anti-CD20 antibody [44] Ianalumab: anti-BAFF receptor antibody [45] Iguratimod: MIF inhibitor [46,47] Abatacept: CD80/86:CD28 costimulation inhibitor [48,49] |
Limited studies on efficacy and safety with often conflicting results [42,43,44,45,46,47,48,49]. |
| RSLV-132 | RNAse targeting IFN [55] | Improved severe fatigue in Sjogren’s [55]. Non-serious side effects like fatigue and infections [55]. |
| RGN-259 | Anti-inflammatory, anti-apoptotic, and wound healing properties through thymosine β4 activity [58] | Reported excellent safety profile [58,59] Pending additional dry eye trial (ARISE-4) in 2023 [59]. |
| Mesenchymal Stem Cells and Exosomes | Immunomodulation, regeneration | May restore gland function. Exosomes are more accessible. Stem cells limited by donor compatibility and preparation. |
| Dexamethasone Subconjonctival Implant (Surodex) | Immunosuppression through NF-κB suppression and phospholipase A inhibition [60] | Sustained drug delivery locally Better patient compliance Currently undergoing phase III studies for prevention of corneal graft rejection. |
| Cyclosporine A Subconjunctival Implants | Immunomodulation and anti-inflammation via calcineurin inhibition [64,65] | Studies showing encouraging results in animals [64,65] |
| Iodide Iontophoresis | Use of mild electric charges applied to drug molecules allowing for passage into anterior and posterior segments [66,67] | Higher bioavailability Reduced clearance of active ingredients Better compliance than ocular injection Further studies needed to determine specific dosage and applicability to other active pharmaceutical compounds |
| Dexamethasone Iontophoresis | ||
| Chitosan Nanoparticles Containing Cyclosporine A | Immunomodulation and anti-inflammation via calcineurin inhibition [68] | Sustained therapeutic drug concentrations in corneal and conjunctival tissues |
| Azithromycin Liposomes | Immunomodulatory and anti-inflammatory effects through decreased NF-κB, IL-6, IL-8, and MMP-2 activity, and increased TGF-β1 | Reduced symptoms of dry eyes in rats Studies remain to be done in SS |
| Dendrimer Drug-Delivery | Nanocarriers that can be customized to accommodate different drug molecules [70,71] | No research has been done applying to dry-eye treatment Successful cross-linkage of active products used in dry-eye treatment |
| Nanowafers | Nanodisc formulation intended to be smeared on ocular surface with fingertips [60,69] | Continuous drug release to anterior ocular surface Improved residence time and bioavailability Studied to reduce inflammation markers of cornea in mice. |
| Fluocinolone Acetonide Intravitreal Implant | Drug-eluting device inserted into vitreous humor [74] | Prolonged drug release Existing technology having received FDA approval. One case report of use for treatment of SS |
| Not utilized | ||
| Immunomodulators | Infliximab: TNF-a inhibitor [50] Etanercept: TNF-a inhibitor [50] Anakinra: IL-1 antagonist [51] Tocilizumab: IL-6 receptor agonist [52] Filgotinib: JAK-1 inhibitor [53] Ianraplenib: STK inhibitor [53] Tirabrutinib: BTK inhibitor [53] Baminercept: Lymphotoxin-b receptor fusion protein inhibitor [54] |
Found ineffective in Sjogren’s disease [50,51,52,53,54] |
| Microneedle Drug-Delivery | Application of microneedle coated with active ingredients to anterior or posterior ocular segments [72] | Further studies needed to establish potential clinical use |