Tauber Eye Center

To report the first known use of combined decellularized Descemet membrane anterior keratoplasty with penetrating keratoplasty (PKP) in a pediatric patient. A 2-month-old boy with bilateral sclerocornea underwent bilateral sequential PKP. In the left eye, PKP performed at 2 months of age was complicated by a persistent epithelial defect postoperatively with a 1 month delay in epithelialization. As a result, the patient underwent PKP with a combined decellularized Descemet membrane corneal allograft implantation in the right eye at 3 months of age to enhance early postoperative healing. This was performed by creating a central 3-mm superficial keratectomy before placing Descemet membrane allograft onto the full-thickness graft. Compared to the 1-month delay in epithelialization after PKP in the left eye, the right eye, which underwent combined PKP and decellularized Descemet membrane corneal allograft, was fully epithelialized by the first postoperative week. The grafts remain clear and intact at 12 months of age. The patient exhibited significant improvement in visual behavior. This case highlights the successful use of decellularized Descemet membrane anterior keratoplasty in preventing a persistent epithelial defect in the early postoperative period for a pediatric patient with sclerocornea. This may be a viable option for similar pediatric cases with delayed epithelial healing while promoting graft survival and minimizing the need for additional surgical interventions.

PurposeThe aim of this study was to evaluate the safety and efficacy of OTX-101, a clear nanomicellar aqueous solution of cyclosporine, in the treatment of dry eye disease (DED).Patients and methodsThis was a 12-week multicenter, randomized, prospective, double-masked, vehicle-controlled, dose-ranging clinical trial. Subjects were adults aged ≥18 years, with a total conjunctival staining score of ≥3 and ≤9, and global DED symptom score ≥40 (0–100 visual analogue scale). Following a 14-day vehicle run-in, subjects were randomized in a 1:1:1 ratio to twice daily treatment with OTX-101 0.09%, OTX-101 0.05%, or vehicle for 84 days. Co-primary efficacy end points were changes, from baseline to Day 84, in the total lissamine green conjunctival staining score in the designated study eye and in the global symptom score (both eyes). Secondary end points included total corneal fluorescein staining score, tear breakup time, and Schirmer’s test score.ResultsIn total, 455 subjects were randomized. Subjects treated with active drug experienced greater improvement in conjunctival staining than vehicle-treated patients (P<0.01 for both concentrations). All groups demonstrated improvements in global symptom score, but there were no differences among groups. Nominally significant differences were found between the active drug arms and vehicle for corneal staining scores and Schirmer’s test scores. Most treatment-emergent adverse events were mild in severity; no serious ocular adverse events were reported.ConclusionsBoth concentrations of OTX-101 met the co-primary sign end point (conjunctival staining) but not the co-primary symptom end point. OTX-101 0.09% demonstrated a notable impact on multiple signs of DED relative to vehicle and was well-tolerated.

Isunakinra, formerly known as EBI-005, is a novel interleukin (IL)-1 receptor inhibitor developed for topical treatment of patients with dry eye disease (DED). This phase 1b/2a multicenter, double-masked, randomized, vehicle controlled environmental trial assessed the safety and biological activity of isunakinra in patients with moderate to severe DED. Subjects (N=74) were randomized to vehicle (placebo) or isunakinra (5 or 20 mg/mL) 3×/daily for 6 weeks. Evaluations included safety, tolerability, biological activity for signs (corneal fluorescein staining [CFS]), symptoms (pain or sore eyes and total Ocular Surface Disease Index [OSDI]), and reduction in rescue artificial tear use. Topical administration of isunakinra (5 and 20 mg/mL) was safe and well tolerated and resulted in clinically relevant improvements in symptoms (OSDI score, painful/sore eye component of OSDI) and signs (total CFS) compared with baseline with no dose response. OSDI scores improved from baseline by 38% (18.9 points) at 6 weeks and CFS scores improved by 33% (3 points) in the isunakinra groups. These changes were not statistically significant compared with the vehicle. Use of artificial rescue tears was significantly reduced in the isunakinra treatment groups (mean=9 vials) compared with vehicle (mean=31 vials). The differences between isunakinra and vehicle treatments were more pronounced in subjects with OSDI scores less than 50 at baseline. Isunakinra was safe, well tolerated and showed clinically meaningful improvements in signs and symptoms of DED. These results encouraged the design of an adequately powered study to characterize the safety and efficacy of isunakinra in ocular surface diseases.

Erratum in Invest Ophthalmol Vis Sci. 2014 Sep;55(9):5588. Miller, William S [coorected to Miller, William L].

Histopathologically, most cases of episcleritis and diffuse or nodular scleritis show chronic, nongranulomatous inflammation with lymphocytes and plasma cells, vascular dilatation, and edema. By contrast, most cases of necrotizing scleritis show chronic granulomatous inflammation with epithelioid cells, multinucleated giant cells, lymphocytes, plasma cells, and less often neutrophils, along with inflammatory microangiopathy. Mast cells and eosinophils can sometimes be seen in the granuloma and around vessels.

In a multicenter, open-label evaluation, 1098 patients with ocular itching and a history of perennial or seasonal allergic conjunctivitis instilled one drop of nedocromil sodium 2% twice daily in each eye. Ocular symptoms, signs, and global improvement were assessed at baseline and 1 month; satisfaction scores, quality-of-life variables, and adverse events were also recorded. Significant improvements from baseline (P<.012) occurred in mean severity scores for itching, burning, stinging, watering, swelling, tired eyes, dryness, gritty sensation, eye pain, foreign-body sensation, and light sensitivity. Physicians reported significant reductions (P<.0001) in bulbar conjunctival redness and swelling. Two thirds of patients (634/954) and three fourths of physicians (710/954) reported at least 75% improvement in overall condition after 1 month. The most common adverse events were burning (2.7%) and unpleasant taste (1.4%); headache (1.2%) and adverse events leading to discontinuation (1.3%) were rare. Patients reported significant improvement (P<.001) in their ability to perform daily activities; 65% were more satisfied with nedocromil than with their typical medication. Physicians would prescribe nedocromil again to 80% of the patients. Nedocromil sodium 2% twice daily was effective and safe for the treatment of symptoms of allergic conjunctivitis, significantly improving quality of life and producing high rates of user and physician satisfaction.