Topical Insulin Eye Drops: Stability and Safety of Two Compounded Formulations for Treating Persistent Corneal Epithelial Defects.

Compounded insulin eye drops were prepared at 1 IU/mL from commercially available subcutaneous insulin by dilution in saline solution or artificial tears. Physicochemical characterization and in vitro tolerance testing in human and conjunctival cells were followed by a 28-day short-term stability study under various conditions. The formulations were isotonic (280-300 mOsm/L), had a pH close to neutral (7-8), medium surface-tension values (<56 MN/m-1), and low (≈1 mPa·s) and medium (≈5 mPa·s) viscosities (compounded normal saline solution and artificial tear-based preparation, respectively). These values remained stable for 28 days under refrigeration. Microbiological stability was also excellent. Insulin potency remained in the 90-110% range in the compounded formulations containing normal saline solution when stored at 2-8 °C for 28 days, while it decreased in those based on artificial tears. Although both formulations were well tolerated in vitro, the compounded insulin diluted in a normal saline solution exhibited better cell tolerance. Preliminary data in humans showed that insulin in saline solution was an effective and safe treatment for persistent corneal epithelial defects. Compounded insulin eye drops diluted in normal saline solution could, therefore, constitute an emergent therapy for the treatment of persistent corneal epithelial defects.

Topical insulin, a novel corneal epithelial regeneration agent in dry eye disease.

OBJECTIVE: To evaluate the efficacy of insulin eye drops for dry eye disease in reducing corneal staining and improving symptoms. METHODS: In this retrospective case series, patients with dry eye disease treated with off-label use of insulin eye drops were collected. The main inclusion criterion was diagnosis of dry eye disease with epithelial damage and acceptance of the off-label use of topical insulin. Age, sex, type of dry eye disease, time since diagnosis, previous ocular surgeries, concomitant treatment, best corrected visual acuity, symptoms, conjunctival hyperemia and corneal staining were recorded. Data from the 1 and 3-month visit were included. RESULTS: 16 patients (32 eyes) were treated with insulin (14 females and 2 males; mean age 61.3 ± 16.8 years). 12 patients (71%) were also on autologous serum and 10 patients (63%) on cyclosporine. Symptoms were 3.4 ± 1.3 (range 2-5) when scaled from 0 to 5. Mean hyperemia was 1.0 ± 0.9 (range 0-3) and corneal staining was 2.5 ± 1.3 (range 0-5). After 3 months, 5 patients (31%) referred to be much better, 6 (38%) better, 3 (19%) slightly better and 2 patients (13%) were subjectively similar, mean symptoms being 2.3 ± 1.0 (range 1-4; p = 0.001). Hyperemia was 0.3 ± 0.4 (range 0-1) and corneal staining was 1.1 ± 1.0 (range 0-3; both p < 0.001). Topical insulin was well tolerated with no adverse events. CONCLUSIONS: The excellent results presented in these case series illustrate topical insulin as a promising treatment in dry eye disease with refractory epithelial damage.

Challenges of DMEK Technique with Young Corneal Donors' Grafts: Surgical Keys for Success-A Pilot Study.

PURPOSE: To report on the surgical maneuvers recommended for a successful unfolding of very young donors in order to accomplish an uneventful Descemet Membrane Endothelial Keratoplasty (DMEK) surgery. METHODS: Five patients (three females and two males, mean age 71.2 ± 6.7 years) with Fuchs endothelial cell dystrophy who underwent DMEK with very young donors (between 20 and 30 years old) were included. The following demographic data were assessed: donor's age, donor's endothelial cell density (ECD), preservation time, recipient's age and sex and unfolding surgical time. Best-corrected visual acuity (BCVA; decimal system), ECD and corneal central thickness (CCT) were assessed preoperatively and at 6-month follow-up. RESULTS: Donors' mean age was 23.6 ± 3.6 years (range 21 to 30) and the mean ECD was 2748.6 ± 162.6 cells/mm2. All of them underwent an uneventful DMEK as a single procedure performed by one experienced surgeon (MAG) with a mean unfolding time of 7.2 ± 4.9 min (range 4 to 15). The essential steps, including patient preparation as well as DMEK graft implantation, orientation, unrolling and centering are detailed. At 6 months, BCVA was 0.6 ± 0.2, ECD was 1945.0 ± 455.5 cells/mm2 and CCT was 497.0 ± 19.7 microns. CONCLUSIONS: We hereby present the keys to overcome tightly scrolled grafts of very young donors, which prove perfectly suitable for DMEK surgery. The graft shape tends towards a double-roll and specific maneuvers are strongly recommended.

Spontaneous Descemet Layer Dissection Without Pneumodissection in Femtosecond Laser-Assisted Mushroom-Type Deep Anterior Lamellar Keratoplasty.

PURPOSE: The aim of this study was to describe a case of spontaneous Descemet layer dissection without pneumodissection in femtosecond laser-assisted mushroom-type deep anterior lamellar keratoplasty. METHODS: This study is a case report. RESULTS: A 46-year-old woman diagnosed with reticular dystrophy underwent, in her left eye, mushroom configuration femtosecond laser-assisted DALK (F-DALK). After laser trephination and removal of the superficial stroma using manual dissection, a type 2 BB formation was observed intraoperatively in the AS-OCT without signs of an associated microperforation. A deeper stromal removal was accomplished by layer-by-layer manual dissection, while the BB persisted. After stromal dissection, the donor cornea was secured with 8 interrupted 10-0 nylon sutures. The next day AS-OCT showed a detachment of DM. After 1 week, a spontaneous resolution of the DM detachment was observed. CONCLUSIONS: This unknown F-DALK intraoperative complication has been detected through intraoperative AS-OCT images which may improve our understanding of F-DALK surgery and possible complications associated with femtolaser-assisted procedures.

Efficacy and safety of topical 5-fluorouracil in conjunctival intraepithelial neoplasia refractory to interferon alpha-2b.

PURPOSE: To report the efficacy and safety of 5-fluorouracil as the second line of treatment for two cases of conjunctival intraepithelial neoplasia refractive to topical interferon alpha-2b. CASE REPORT: In the first case, a 77-year-old woman was evaluated because of a fleshy vascularized lesion in the temporal conjunctiva on her right eye with leukoplakia of the corneal epithelium from 10- to 5-o'clock limbus. In the second case, an 81-year-old man, a nodular lesion in the temporal conjunctiva on his RE, with corneal adjacent opalescence, one millimeter in extent, was observed. Both patients were initially treated with excisional surgery, the samples being reported as conjunctival intraepithelial neoplasia with high-grade dysplasia. Co-adjuvant treatment with topical interferon alpha-2b 1 mIU/mL was indicated 4 times/day uninterruptedly. In the first case, there was no response despite 8 months of treatment, while in the second, the corneal lesion progressed in an arboriform pattern after 4 months of topical chemotherapy. MANAGEMENT & OUTCOME: In the absence of efficacy, the treatment was then changed to topical 5-fluorouracil (1%), 4 times/day for 7 days with a time-lapse of 21 days off, which constitutes a course. Two and four courses of treatment with 5-fluorouracil 1% were completed in both cases in the absence of important side effects. After the first course, both patients showed complete remission of the lesions. No clinical signs of relapse were noted after 1 year of follow-up. DISCUSSION: The treatment with 5-fluorouracil is a good option as the second line of treatment for conjunctival intraepithelial neoplasia who are low-responders to interferon alpha-2b, with fewer side effects than other currently available alternatives.

Conjunctivitis in an Individual With Monkeypox.

This case report describes a case of monkeypox in a patient with HIV presenting with conjunctivitis.

New Horizons in the Treatment of Corneal Endothelial Dysfunction.

The treatment of corneal endothelial dysfunction has experienced a revolutionary change in the past decades with the emergence of endothelial keratoplasty techniques: descemet stripping automated endothelial keratoplasty (DSAEK) and descemet membrane endothelial keratoplasty (DMEK). Recently, new treatments such as cultivated endothelial cell therapy, Rho-kinase inhibitors (ROCK inhibitors), bioengineered grafts, and gene therapy have been described. These techniques represent new lines of treatment for endothelial dysfunction. Their advantages are to help address the shortage of quality endothelial tissue, decrease the complications associated with tissue rejection, and reduce the burden of postoperative care following transplantation. Although further randomized clinical trials are required to validate these findings and prove the long-term efficacy of the treatments, the positive outcomes in preliminary clinical studies are a stepping stone to a promising future. Our aim is to review the latest available alternatives and advancements to endothelial corneal transplant.

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