No therapy is currently FDA approved to treat ocular pain. This study evaluated the safety and efficacy of a novel topical ocular cooling device for chronic ocular surface pain (COSP). This was a prospective, randomized, double-masked, multicenter clinical feasibility study in adults aged 22–90 years with COSP. The intervention was a handheld device that applied cold temperatures to the conjunctival surface above the long ciliary nerves via two metallic contact surfaces at the 3 and 9 o’clock positions. Subjects were randomized 2:1 to a one-time, 4-min treatment with the active (frozen) or sham (refrigerated) device and followed for 8 weeks. Subjective pain was assessed via the visual analog scale (VAS), ocular pain assessment survey (OPAS), and chronic ocular pain questionnaire (COP-Q). Corneal sensitivity was evaluated with Cochet–Bonnet esthesiometry. Main outcomes were change from baseline in VAS, OPAS, and COP-Q scores. Post hoc analyses were conducted in eyes with peripheral-dominant pain based on proparacaine challenge. Adverse events (AEs) were recorded. Unilateral treatments were administered to 31 subjects (20 active, 11 sham). All three patient-reported outcomes (PROs) showed greater reductions in eye pain at week 8 in the active versus sham arm. In eyes with peripheral-dominant pain, COP-Q eye pain severity improved significantly versus sham at week 8 (nominal p = 0.042), and OPAS overall eye pain trended towards statistical significance (nominal p = 0.088). All three PROs exceeded thresholds for clinically meaningful improvement. Baseline corneal sensitivity was below normal in both groups and improved significantly only in the active group (nominal p = 0.041). No serious AEs occurred; the most common AE was transient conjunctival hyperemia. A novel ocular surface cooling device is well tolerated and appears to provide durable relief of COSP in peripheral-dominant pain types for at least 8 weeks. ClinicalTrials.gov identifier: NCT06479382.
PURPOSE:To evaluate the safety and efficacy of dazdotuftide (TRS01 eye drops), a novel, steroid-free, anti-inflammatory drug in patients with active anterior noninfectious uveitis (NIU), following previous studies in which it had shown a favorable risk/benefit profile with regards to safety and specifically intraocular pressure (IOP) safety profile. DESIGN:A randomized, double-masked, multicenter, active-controlled phase 3 trial. PARTICIPANTS:Adults (≤75 years of age) and pediatric patients, with active anterior NIU, with or without uveitic glaucoma, on stable medical therapy for NIU or who had received no prior therapy, requiring further treatment for an active NIU flare-up. Patients eligible for inclusion had Anterior Chamber Cell (ACC) Grade 2 or Grade 3 on Visual Analog Scale in the study eye. METHODS:Patients were randomized 2:1 to topical TRS01 1% or prednisolone acetate 1% administered 4 times daily for 28 days. Key ocular assessments included slit-lamp examination, ocular pain, Best Corrected Visual Acuity, IOP and dilated ophthalmoscopy. MAIN OUTCOME MEASURES:Resolution of inflammation (ACC = 0), clinically meaningful improvement of ACC, ocular pain, flare, and IOP changes on Day 28. RESULTS:The Full Analysis Set included 136 patients; the mean age was 43 years in the TRS01 arm and 42 years in the prednisolone acetate arm. 48% of TRS01 vs 68% of prednisolone acetate patients achieved ACC Grade = 0 on Day 28 (95.1% Confidence Interval (CI): -0.37, -0.02; P = .0311) and 64% of TRS01 vs 89% prednisolone acetate patients experienced clinically meaningful improvement of ACC Grade = 0 or 1, ie, ≤5 cells (95.1% CI: -0.33, -0.06; P = .0049). While TRS01 was found to be inferior to topical steroids to control ACC, TRS01 was noninferior to topical steroids to control flare and ocular pain and exhibited a superior IOP safety compared to topical steroids. For patients who reached ACC = 0, TRS01-treated patients benefited from statistically significantly improved safety outcomes for IOP (including change from baseline and at each IOP threshold evaluated [P < .05]) versus steroid-treated patients. CONCLUSIONS:TRS01 offers the potential to serve as an effective and safe treatment option in NIU that meets the urgent need for a drug that controls inflammation without the steroids' associated risk of IOP elevation.
PURPOSE:The American Society of Cornea and Refractive Surgery Cornea Committee convened to create a brief review of the literature and expert experience of antibody-drug conjugates (ADCs) and their impact on ocular surface health. METHODS:Peer-reviewed publications from 2003 to 2025 were evaluated. The information along with authors clinical experience was used to create a white paper on the current aspects ADC therapy that is relevant to the ocular surface health. RESULTS:There are currently 14 Food and Drug Administration-approved ADCs. By most recent estimates in the literature, there are more than 200 ADCs currently in development, and a significant proportion of them are associated with keratopathy that has unique ocular surface manifestations. Features of ADC-induced keratopathy include corneal pseudocysts, superficial punctate keratitis, refractive shifts, and conjunctival hyperemia. More severe adverse events such as conjunctival hemorrhage, conjunctival scarring, and corneal ulcers are rare. These findings correlate with change in visual acuity and visual quality. Eye care providers need guidance to recognize, understand, and communicate critical features of vision health with referring oncologists. CONCLUSIONS:Given the anticipated surge in oncology patients on ADCs, there is a need for dissemination of information on ocular surface concerns. This review covers key aspects ADC toxicity mechanisms and pathological features on the ocular surface health including strategies to diagnose, grade, and treat disease. It also provides expectations on the eye care provider's role in communication with referring oncologists.
PURPOSE To determine outcomes of minimally invasive glaucoma surgeries (MIGS) and traditional incisional glaucoma surgeries (TIGS)—trabeculectomy and glaucoma drainage devices—in IRIS® Registry (Intelligent Research in Sight). DESIGN Retrospective cohort study. SUBJECTS Age ≥18 years with open-angle glaucoma who underwent MIGS or TIGS. METHODS We identified patients in the IRIS Registry who had MIGS or TIGS between 2014-2018 and at least 1-year of follow-up. Inclusionary criteria included diagnosis of open-angle. MAIN OUTCOME MEASURES Co-primary outcomes included success rates at 1 year, defined as intraocular pressure (IOP) ≤14, ≤18, or ≤21 mmHg or IOP reduction ≥20%; IOP not ≤5 mmHg at 2 consecutive visits; no additional glaucoma surgery; and no loss of light perception. Additional outcomes included mean IOP and medications at 1 year. RESULTS After the inclusion/exclusion criteria, there were 56,915 MIGS eyes and 17,983 TIGS eyes (total 74,898 eyes from 56,136 patients). MIGS success rates at 1 year were low using targets of IOP ≤14 mmHg (43%) or reduction ≥20% (25%) and were higher with ≤18 mmHg (80%) and ≤21 mmHg (91%). Although TIGS had greater success at achieving IOP ≤14 mmHg (54%) and reduction ≥20% (59%), they were significantly lower than MIGS with ≤18 mmHg (77%) and ≤21 mmHg (85%). Adjusted IOPs for MIGS were 16.49 (95% CI 16.27, 16.71) pre-treatment and 14.84 (95% CI 14.65, 15.03) at 1 year. For TIGS, adjusted IOPs went from 23.54 (95% CI 22.91, 24.17) to 14.00 (95%CI: 13.62, 14.37). Adjusted medication changes were from 2.06 (95% CI 1.99, 2.12) to 2.19 (95% CI 2.11, 2.26) and 3.38 (95% CI 3.27, 3.48) to 2.78 (95% CI 2.67, 2.88) for MIGS and TIGS, respectively. Rates of severe complications (endophthalmitis, suprachoroidal hemorrhage, hypotony/flat anterior chamber, retinal detachment) were substantially lower in the MIGS group (P<0.05 for all). CONCLUSIONS MIGS success in achieving low IOPs (≤14) or reduction ≥20% was low but higher with cutoffs of ≤18 and ≤21. With TIGS, there was good success at all the cutoff values (>50%). Both groups had significant reductions in IOP, with TIGS having a significant reduction in medications at 1 year. MIGS had less severe complications.
The introduction of anti-vascular endothelial growth factor (VEGF) therapies changed the treatment landscape for neovascular age-related macular degeneration (nAMD), slowing the progression of central vision loss. However, current anti-VEGF therapies are limited by the need for frequent intravitreal injections to maintain disease control, which places a substantial burden on patients, caregivers, and healthcare systems, and contributes to poorer treatment adherence and persistence in the real-world setting. To extend the dosing interval, flexible dosing strategies were implemented; however, they carry the risk of both undertreatment and overtreatment. Emerging longer-acting strategies include continuous-release delivery systems (e.g. ranibizumab port delivery system) and gene therapy. Investigational gene therapies have been designed to preferentially target non-dividing retinal cells, enabling sustained expression of a therapeutic protein for the lifespan of these cells. While the therapeutic effect is designed to persist for years following the one-time administration of gene therapy, early clinical trials show that a subset of patients do receive supplemental anti-VEGF injections. Emerging patterns of retreatment support the concept that supplemental treatment does not necessarily indicate waning efficacy, but rather the adjuvant treatment may be used transiently to fine tune for increased disease activity levels at the patient level. In summary, multiple factors need to be considered to understand the durability of future therapies, not only reduced procedural frequency but also continuous disease control and improved quality of life - key metrics that will guide the evolution of care in nAMD.
