Safety and efficacy of topical interferon alpha 2B and mitomycin C for localized conjunctival intraepithelial neoplasia: long-term report of their pharmacological safety and efficacy.

PURPOSE: Ocular surface squamous neoplasia (OSSN) comprises a wide spectrum of squamous tumors, from which corneal/conjunctival intraepithelial neoplasia (CIN) is the most common one. The classic treatment is complete excision, but recurrence rates are high. Antineoplastic drugs such as mitomycin C (MMC) and interferon alpha 2b (IFNα2b) have been used as adjuvants or as primary treatment. To evaluate the efficacy and safety of topical IFNα2b and MMC in patients with CIN, a phase IIb double-blind clinical trial was performed. METHODS: Patients diagnosed with localized CIN were evaluated by slit lamp and impression cytology and were randomly given MMC 0.04% or INF2b (1 million IU/mL) 4 times daily until neoplasia resolution. Time of resolution and frequency of adverse effects were analyzed to determine the pharmacological efficacy and safety of both medications. RESULTS: Seventeen patients were included. Nine patients were treated with MMC and 8 with IFNα2b. All patients responded to treatment. The resolution time in days was 59.11 ± 24.02 in patients treated with MMC and 143.50 ± 47.181 in those treated with IFNα2b (p < 0.001). In the MMC group, one recurrence was reported (11%). There were no recurrences at 2 years of follow-up in the IFNα2b group. Regarding adverse effects, one or more mild adverse reaction occurred in 77% of patients managed with MMC and in 50% of patients managed with IFNα2b (p > 0.05). No serious adverse effects were reported. CONCLUSIONS: Topical chemotherapy with MMC and IFNα2b demonstrate pharmacological safety and efficacy. Therefore, these drugs could be considered as primary therapies for localized CIN .

Topical Pirfenidone-Loaded Liposomes Ophthalmic Formulation Reduces Haze Development after Corneal Alkali Burn in Mice.

Corneal chemical burns (CCBs) frequently result in corneal fibrosis or haze, an opacity of the cornea that obstructs vision and induces corneal blindness. Diverse strategies have been employed to prevent or reduce CCB-related corneal haze. In this study, we evaluated the physicochemical characteristics and biologic effects of a topical pirfenidone (PFD)-loaded liposomal formulation (PL) on a corneal alkali burn mice model. We found that PL was appropriate for ocular application due to its physiologic tear pH, osmolarity and viscosity suitable for topical ophthalmic use. Regarding its therapeutic activity, PL-treated mice had significantly reduced haze size and density, corneal edema, corneal thickness, and corneal inflammatory infiltration, in contrast to PFD in aqueous solution (p < 0.01). Importantly, the antifibrotic activity of PL (reduction of corneal haze) was associated with modulation of transforming growth factor (TGF)-ß and Interleukin (IL)-1ß genes. PL suppressed TGF-ß expression and restored normal IL-1ß expression in corneal tissue more efficiently in contrast to PFD in aqueous solution. In conclusion, PFD showed essential anti-inflammatory and anti-fibrotic effects in the treatment of alkali burns. Noteworthy, a new formulation of PFD-loaded liposomes remarkably improved these effects, standing out as a promising treatment for corneal haze.

Experimental design of a culture approach for corneal endothelial cells of New Zealand white rabbit.

The harvesting of corneal endothelial cells (CEC) has received special attention due to its potential as a therapy for corneal blindness. The main challenges are related to the culture media formulation, cellular density at the primary isolation, and the number of passages in which CEC can retain their functional characteristics. To alternate different media formulations to harvest CEC has an impact on the cellular yield and morphology. Therefore, we analyzed four different sequences of growth factor-supplemented Stimulatory (S) and non-supplemented Quiescent (Q) media, upon passages to find the optimal S-Q culture sequence. We assessed cell yield, morphology, procollagen I production, Na+/K+-ATPase function, and the expression of ZO-1 and Na+/K+-ATPase. Our results show SQSQ and SQQQ sequences with a balance between an improved cell yield and hexagonal morphology rate. CEC cultured in the SQQQ sequence produced procollagen I, showed Na+/K+-ATPase function, and expression of ZO-1 and Na+/K+-ATPase. Our study sets a culture approach to guarantee CEC expansion, as well as functionality for their potential use in tissue engineering and in vivo analyses. Thus, the alternation of S and Q media improves CEC culture. SQQQ sequence demonstrated CEC proliferation and lower the cost implied in SQSQ sequences. We discarded the use of pituitary extract and ROCK inhibitors as essential for CEC proliferation.