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Background: This study evaluates the therapeutic efficacy of HAr® (a novel ophthalmic solution containing modified hyaluronic acid covalently linked to riboflavin) compared to hyaluronic acid eye drops in patients with dry eye disease (DED). Methods: Sixteen consecutive patients with bilateral medium to severe DED were divided into two groups. Group 1 received HAr® 0.1 % (Ribohyal®), while Group 2 received HA 0.1 % eye drops. Parameters such as Ocular Surface Disease Index (OSDI) score, osmolarity, break-up time (BUT), non-invasive BUT (NIBUT), tear meniscus measurement, Schirmer test, and Oxford Staining were evaluated. This study has been successfully registered on ClinicalTrials.gov public (Identifier NCT06122428) Results: The Ribohyal group showed faster improvement in OSDI scores, with a statistically significant difference at 2 h (mean classification difference: −51.75; p = 0.0003). Photophobia significantly reduced at 2 h, 4 weeks, and 8 weeks in the Ribohyal group compared to baseline (p < 0.0001). Osmolarity improved significantly after 8 weeks in both groups (p < 0.0001). Conclusions: HAr® 0.1 % (Ribohyal®) effectively reduced DED symptoms and improved photophobia within 2 h of instillation, lasting up to 8 weeks.