The goal of this study is to evaluate whether Quantum Molecular Resonance (QMR) treatment can effectively reduce eye pain and stimulate corneal nerve regeneration in patients with neuropathic corneal pain (NCP). Participants diagnosed with NCP will attend a total of nine study visits, consisting of one baseline assessment and eight QMR treatment sessions. At each visit, participants will undergo a series of clinical examinations to evaluate changes in the ocular surface, corneal nerves, and tear proteins, and will complete questionnaires regarding their symptoms, eye pain, and quality of life. The investigators will compare these outcomes before and after QMR treatment to determine whether QMR treatment alleviates NCP symptoms and enhances ocular surface and corneal nerve health. The investigators hypothesize that QMR treatment will provide notable pain relief, promote corneal nerve regeneration, and improve overall quality of life for NCP patients.

Neuropathic corneal pain (NCP) is a severe and challenging condition resulting from dysfunctional corneal nerves, with a range of non-specific symptoms. Patients with NCP often experience burning, aching, shooting, or stabbing pain without corresponding clinical signs, and the symptoms are typically unresponsive to conventional dry eye treatments. NCP is associated with various conditions, including dry eye disease, diabetic corneal neuropathy, herpes simplex keratitis, recurrent corneal erosion syndrome, radiation keratopathy, trauma, and ocular surgeries such as cataract or refractive procedures. Psychological conditions like depression and anxiety, and chronic pain states such as fibromyalgia and trigeminal neuralgia, predispose patients to NCP. The effects of NCP can range from mild discomfort impacting daily activities to severe symptoms that significantly impair physical and social well-being. Patients with NCP typically show reductions in morphologic metrics, including corneal nerve fiber length and density, which can be assessed using in vivo confocal microscopy (IVCM). In addition, microneuromas, characterized by irregularly shaped enlargements of terminal nerve endings with poorly defined margins and variable hyper-reflectivity on IVCM, are dynamic indicators of corneal neuropathological recovery.

Treatment of NCP is challenging due to its complex and varied pathophysiology, often requiring multiple approaches. Effective management aims to alleviate pain in the short term and address central sensitization in the long term. Management typically involves anti-inflammatories, nerve-regenerating agents, and mental health support, including artificial tears, topical steroids, autologous serum tears, cryopreserved amniotic membrane, and bandage contact lenses. However, these treatments have drawbacks, and many patients experience persistent pain despite these approaches. This highlights a critical need for novel treatment approaches to address the complexity of NCP more effectively.

Quantum Molecular Resonance (QMR) is an innovative technology that utilizes transpalpebral, non-invasive, high-frequency microcurrent electrical stimulation, promoting the natural regeneration of cells. By applying low-power, high-frequency oscillating electrical currents within the range of 4 to 64 megahertz, QMR leverages the resonance effect to optimize energy delivery to biological tissues. Remarkably, this process achieves significant biological responses without increasing tissue temperature. QMR modulates cellular inflammatory responses by down-regulating pro-inflammatory cytokines while simultaneously upregulating anti-inflammatory ones. The energy package delivered by QMR significantly alters intra- and extracellular ions, changing the transmembrane potential and triggering stem cell replication, and leading to asymmetric regeneration of new stem cells. The Rexon-Eye (Resono Ophthalmic, Sandrigo, Italy) is a QMR-based electrotherapy device developed in 2014. It received Conformité Européene marking in 2016 as a medical device for ocular surface disorders and has patents in Italy and Europe, as well as Health Sciences Authority approval in Singapore. The therapy involves applying specialized mask electrodes to the periorbital area for 20-minute sessions, and it stimulates cellular regeneration and reactivates the lacrimal system, particularly in treating dry eye disease. Previous studies have demonstrated a significant reduction in corneal epithelial damage and an improvement in subjective ocular surface symptoms, as measured by the Ocular Surface Disease Index (OSDI) after treatment compared to placebo, with no reported adverse effects. Furthermore, it has been found that electrical stimulation treatments can effectively reduce ocular pain intensity and improve corneal sensitivity.

The investigators aim to evaluate the efficacy of QMR treatment in alleviating symptoms of NCP and promoting corneal nerve regeneration. The underlying molecular mechanisms by which QMR exerts its effects, including its influence on neuroinflammatory pathways and nerve function, will also be explored.

Inclusion Criteria:

• Be at least 21 years of age.
• Regardless of gender (Male/Female).
• Regardless of race (Chinese/Malay/Indian/Eurasian/Others).
• Diagnosed with neuropathic corneal pain based on the following criteria: presence of neuropathic ocular symptoms (burning, stinging, photophobia, pain, severe dryness), absent or minimal slit-lamp findings to explain the symptoms and corneal nerve abnormalities as detected by IVCM (decreased corneal length and density, presence of neuromas).
• Willing to receive all eye examinations in this study.

Exclusion Criteria:

• Pregnant women.
• Participants carrying active implantable devices (e.g., pacemakers and hearing aids).
• Oncologic patients under treatment; patient who underwent ocular surgery in the last month.
• Participants who had ocular infection within 6 months, or active ocular infection or inflammation; any concomitant ocular diseases that could potentially induce ocular pain, such as uveitis.