Hyaluronic Acid vs Mitomycin-C in External Dacryocystorhinostomy

Dacryocystorhinostomy (DCR) is the standard procedure for nasolacrimal duct obstruction achieving a success rate ranging between 80-95%, aimed at restoring tear drainage by creating a direct passage between the lacrimal sac and middle meatus of the nasal cavity (1). However, postoperative failure due to fibrosis and ostium closure due to excessive fibroblast proliferation and extracellular matrix deposition, remains a major concern (2). To counteract fibrosis, various adjuncts such as Mitomycin-C (MMC) and Hyaluronic Acid (HA) have been used. Mitomycin-C was discovered from the cultures of Streptomyces caespitosus. It is an alkylating drug that inhibits DNA from being transcribed into RNA by creating cross-links within DNA strand, thus inhibiting the protein synthesis; primarily useful as a chemotherapeutic drug. It can also inhibit fibroblast proliferation, thus paving its way as an anti-adhesive in various surgeries in ophthalmology such as strabismus surgery, pterygium surgery, trabeculectomy, DCR, corneal refractive surgeries, etc. Mitomycin-C (0.4 mg/ml) soaked in gelfoam is applied at the ostium site for 2 minutes and then thoroughly irrigated with normal saline in DCR as it can lead to punctal or canalicular stenosis, conjunctival thinning, delayed wound healing, excessive nasal crusting or synaechiae (3). Systemic absorption causing myelosuppression, mucositis, hepatorenal toxicity can also occur if not irrigated thoroughly.

Hyaluronic Acid is a glycosaminoglycan (GAG) polysaccharide which is a naturally occurring chemical which is the main component of extracellular matrix. It is found in skin, connective tissue, synovium, umbilical cord and vitreous humor. Hyaluronic acid activates CD 44 mediated Rho/ MAPK/ PI3K signaling pathways, promoting controlled epithelial migration, proliferation and extracellular matrix deposition. Hyaluronic acid maintains a moist extracellular environment, promoting epithelial migration and mucosal regeneration over raw bone and granulation tissue. It enhances cilia recovery and muco-ciliary clearance in the nasal cavity.

Matrix Metalloproteinase-9 (MMP-9), also known as Gelatinase B, is a zinc- and calcium-dependent enzyme that degrades components of the extracellular matrix, particularly type IV collagen of the basement membrane. It is secreted as an inactive pro-enzyme by fibroblasts, epithelial cells, and inflammatory cells and becomes activated by proteolytic cleavage. MMP-9 facilitates cell migration, angiogenesis and tissue remodeling during normal wound healing. However, excessive or prolonged activity leads to excess matrix breakdown, chronic inflammation and fibrosis, especially when the balance between MMP-9 and its inhibitor TIMP-1 is disrupted. In DCR surgery, optimal MMP-9 activity supports mucosal healing, while overexpression promotes granulation and ostium closure. Hence, tear MMP-9 levels serve as an indicator of postoperative healing and fibrosis modulation.

Since tear fluid reflects local ocular surface and lacrimal system changes, evaluating MMP-9 levels before and after DCR provides an objective measure of fibrosis modulation (4). This study aims to compare the surgical success rates of DCR when using intraoperative MMC versus HA, along with evaluating their effects on tear MMP-9 levels.

GAPS IN CURRENT LITERATURE:

While multiple studies have examined the roles of Mitomycin-C (MMC) and Hyaluronic Acid (HA) in DCR to minimize postoperative fibrosis and ostium blockage, the available data is still sparse and varies widely across reports. Both MMC and HA have individually been studied for their anti-fibrotic effects in DCR. To date, there is a lack of controlled study that provides a direct comparison between the two agents. Also, most studies have focused primarily on anatomical and functional success rates without assessing the underlying molecular mechanisms of wound healing. There is a paucity of data evaluating objective biochemical markers such as Matrix Metalloproteinase-9 (MMP-9) or Tissue Inhibitors of Metalloproteinases (TIMPs) to quantify the degree of fibrosis or inflammation following DCR. Hence, there is a significant gap in evidence regarding the relative efficacy and safety of MMC versus HA in preventing post-operative fibrosis and ostium closure following DCR surgery.

Objectives:

Primary objective:

To compare the surgical success in patients undergoing external dacryocystorhinostomy with intraoperative Mitomycin-C (0.4 mg/ml) Vs Hyaluronic acid 1% (1ml) as adjuvant

Secondary objectives:

1. To compare the complication rates and wound healing patterns in each group 2. Change in tear MMP-9 levels from preoperative (within 1 week before surgery) to postoperative (6 weeks after surgery) 3. To compare the comfort levels of patients in each group

• MMP-9 levels using ELISA [Time frame: 6 months]
• Patient Satisfaction Scale (Visual Analog Scale) [Time frame: 6 months]