Weak and uncontrolled. A single case report of recurrent filamentary keratitis refractory to lubricants, punctal plugs, steroids, and lid hygiene showed complete filament resolution and symptom relief sustained at 10 months on a compounded 10% solution given with preservative-free ointment and oral doxycycline, and a systematic review of 106 ocular studies found 5% to 10% four times daily the most common regimen with rare corneal necrosis at higher concentrations.

Very weak. Two case reports used topical 5% inside a multimodal regimen of topical corticosteroid, lid hygiene, and low-level light therapy, and the authors state the contribution of the light therapy cannot be determined from these findings alone, and the acetylcysteine contribution is likewise unisolated.

The phase 2 randomized, double-masked, vehicle-controlled dose-ranging trial (81 TID, 82 BID, 84 vehicle, including Sjogren dry eye) missed its primary endpoint: change in Schirmer I at week 4 did not differ from vehicle (TID difference 0.93 mm, 95% CI -1.47 to 3.32, P=0.078; BID 2.31 mm, 95% CI -0.08 to 4.70, P=0.066, 1-sided alpha 0.025). Symptom scores (SANDE) fell significantly with TID only, and the authors conclude that larger studies are warranted.

Single-center randomized double-masked vehicle-controlled trial: 32 enrolled, 16 analyzed (10 treated, 6 vehicle). SANDE symptom score fell 26.0 mm versus a 3.2 mm rise on vehicle (p=0.049) and median unanesthetized Schirmer rose 0.5 mm versus a 3 mm fall (p=0.014) at 4 weeks, while OSDI, corneal fluorescein staining, tear breakup time, and lid margin measures did not separate and temporal lissamine green staining was the only stain measure that did (p=0.048); the authors describe the trial as underpowered after a 50% dropout. A retrospective single-institution cohort of 18 allogeneic transplant recipients reported improved NIH ocular GVHD severity scores in 8 (44%). A single case report describes bacterial keratitis and corneal perforation requiring evisceration in a chronic GVHD patient on this drug, which its authors judged strongly associated with the drug by drug accountability criteria; the product owner and the authors then published replies to each other.

Randomized, no-treatment-controlled study in 52 adults with symptomatic dry eye and a Korb lid wiper epitheliopathy score of 1.0 or greater: Korb and photographic LWE grades were significantly better than no treatment from week 2 onward, as were SPEED and symptom scores at 2 months, but the 0.5-unit or greater photographic improvement at 2 months reached significance in right eyes only (P=0.04). The authors state masked comparative trials are still needed.

Three small vehicle-controlled trials from one investigator group, randomized per the published reports (LASIK n=40, PRK n=41, crosslinking n=20): no primary endpoint reached statistical significance in any of the three, leaving only directional trends in corneal staining, tear osmolarity, and epithelial closure. The LASIK report concluded that a larger trial is needed.