Refractory Ocular Surface Disease As A Systemic Immunometabolic Manifestation: A Two-Case Integrative Approach

To report two cases of refractory ocular surface disease (OSD) in which a combined local and systemic integrative approach achieved clinically meaningful outcomes beyond conventional topical therapy. Both cases presented with elevated systemic inflammatory markers, suggesting that unresolved low-grade chronic inflammation may perpetuate local ocular disease. We propose a three-level therapeutic model integrating local intervention, metabolic e inmunologic optimization, and gut-eye axis modulation as a framework for the management of refractory OSD.

Two female patients evaluated at an ophthalmology outpatient practice with an integrative medicine approach. Assessments included slit-lamp biomicroscopy, TBUT, corneal staining (Oxford grading), visual acuity (VA), and a Cellular Inflammatory Profile (CIP) — a dried blood spot fatty acid panel quantifying the AA:EPA ratio, omega 3 index, and key inflammatory mediators as markers of systemic pro-inflammatory load.

Case 1: 62-year-old female with refractory inflammatory dry eye, corneal degeneration, ocular rosacea, high astigmatism (VA 0.2), conjunctival hyperemia, peripheral vascularization, TBUT 5s, and elevated CIP (fatty acid and inflammatory mediator profile). Local therapy: corticosteroids, cyclosporine, topical insulin eye drops, IPL + periocular PBM. Significant symptomatic improvement and visual comfort were achieved with the integration of systemic interventions — high-dose omega-3 (3g/day), anti-inflammatory nutrition, stress management — supporting a synergistic local-systemic approach. Outcomes: hyperemia resolution, VA stabilization, marked OSDI reduction, CIP normalization, mood improvement.

Case 2: 28-year-old female with severe ocular/nasal allergy, peripheral corneal vascularization, TBUT 7s, tarsal inflammation, hyperemia, itching, tearing, photosensitivity, arthralgias, headache. Systemic profile: elevated CIP, IgE 1660 IU/mL, C3 136 mg/dL (elevated), Vitamin D 38 ng/mL (insufficient). Spontaneous remission during pregnancy with postpartum relapse confirms immune-hormonal systemic dominance. Conventional topical therapy combined with systemic interventions — high-dose omega-3 (3g/day), low-histamine diet, glutamine 5g twice daily — resulted in progressive and sustained clinical improvement. Outcomes: regression of tarsal inflammation, hyperemia and vascularization; resolution of ocular symptoms; marked reduction in arthralgias, headache, and nasal symptoms.

Both cases support the hypothesis that refractory OSD may be perpetuated by systemic low-grade chronic inflammation insufficiently addressed by local therapy alone. Improvement in extra-ocular manifestations — mood, arthralgias, nasal symptoms — alongside ocular outcomes suggests a shared systemic inflammatory substrate. In Case 2, absence of phototherapy with significant multi-domain improvement strengthens the argument for systemic immunometabolic modulation. CIP normalization in both cases provides objective evidence of systemic response, supporting its integration into OSD clinical assessment.