One-Year Results of a Phase I/II Randomized, Double-Masked, Placebo-Controlled Study of Processed Amniotic Fluid Drops After PRK.

PURPOSE: The aim of this study was to evaluate the 1-year outcomes of using processed amniotic fluid (pAF) postoperatively after photorefractive keratectomy (PRK). METHODS: Sixty-one participants were randomized to receive either placebo or pAF drops. The drops were instilled 4 times daily for 1 week after PRK along with routine postoperative medications. The primary outcome measures included uncorrected visual acuity, topographic corneal irregularity measurement, and surface staining over 1 year. RESULTS: A statistically significant difference in uncorrected distance visual acuity between the placebo and treatment groups was seen at 1 month post-PRK, with a visual advantage evident in the pAF group. A suggestive difference in corneal irregularity measurement was also seen between the placebo and treatment groups at 1 month postsurgery, with less irregularity noted in the pAF group. No differences in uncorrected distance visual acuity or corneal irregularity measurement were found at 3, 6, and 12 months. There was also no significant difference in corneal staining scores between the 2 groups at any of the measured time points. CONCLUSIONS: This 1-year study evaluating the safety and efficacy of pAF as an additional postoperative topical medication after PRK demonstrated that pAF offered a mild visual advantage at 1 month post-PRK. There were no late adverse events, and the intervention proved safe at 1 year.

Phase I/II randomized, double-masked, placebo-controlled study of processed amniotic fluid drops after PRK.

PURPOSE: To evaluate the safety and efficacy of processed amniotic fluid (pAF) used postoperatively after photorefractive keratectomy (PRK). SETTING: University of Utah, Moran Eye Center, Salt Lake City, Utah. DESIGN: Randomized, double-masked, placebo-controlled prospective study. METHODS: 61 participants were randomized to receive either placebo or pAF drops, which were instilled 4 times per day for 1 week after PRK along with routine postoperative medications. The primary outcome measure was time to full re-epithelialization in days. Secondary measures included visual acuity at 30 days and postoperative pain scores during the first week. RESULTS: There was no significant difference in time to re-epithelialization, with a median of 5 days for both groups. There were no difference in pain indicator scores during the first week and no difference in corneal staining scores at day 30 between the 2 groups. There were no adverse events. CONCLUSIONS: This pilot study evaluating the safety and efficacy of pAF as an additional postoperative topical medication for PRK demonstrated that pAF did not improve the rate of epithelial healing after PRK. pAF may be safely studied in other ocular conditions to determine its effect on epithelial healing.

Peripapillary Neuroendocrine Carcinoma Metastasis: A Novel Approach to Treatment.

Peripapillary and circumpapillary retinal intraocular metastases are rare and present a treatment challenge for ophthalmologists because of the high risk of iatrogenic injury to the optic nerve. There are no clear guidelines on the management of these lesions, and many clinicians will initially observe for improvement of the metastases with systemic chemotherapy before considering local therapy with external beam radiation. Radiation to the optic disc carries a significant risk of injuring the optic nerve, leading to worsening of vision. Alternative treatment approaches are needed. We present a patient with large-cell neuroendocrine carcinoma with metastasis to the peripapillary retina who was treated with intravitreal topotecan and with intravitreal aflibercept. Serial fundus photos, ultrasound, and optical coherence tomography demonstrated a reduction in size of the lesion and a decrease in subretinal fluid with intravitreal topotecan and aflibercept. In addition, visual acuity was stabilized during treatment. Intravitreal chemotherapy for intraocular metastases in vision-sensitive areas such as the peripapillary retina may be a viable alternative for patients who seek to preserve their vision and maintain their quality of life.

Oxidative stress-mediated NFκB phosphorylation upregulates p62/SQSTM1 and promotes retinal pigmented epithelial cell survival through increased autophagy.

p62 is a scaffolding adaptor implicated in the clearance of protein aggregates by autophagy. Reactive oxygen species (ROS) can either stimulate or inhibit NFκB-mediated gene expression influencing cellular fate. We studied the effect of hydrogen peroxide (H2O2)-mediated oxidative stress and NFκB signaling on p62 expression in the retinal pigment epithelium (RPE) and investigated its role in regulation of autophagy and RPE survival against oxidative damage. Cultured human RPE cell line ARPE-19 and primary human adult and fetal RPE cells were exposed to H2O2-induced oxidative stress. The human apolipoprotein E4 targeted-replacement (APOE4) mouse model of AMD was used to study expression of p62 and other autophagy proteins in the retina. p62, NFκB p65 (total, phosphorylated, nuclear and cytoplasmic) and ATG10 expression was assessed by mRNA and protein analyses. Cellular ROS and mitochondrial superoxide were measured by CM-H2DCFDA and MitoSOX staining respectively. Mitochondrial viability was determined using MTT activity. qPCR-array system was used to investigate autophagic genes affected by p62. Nuclear and cytoplasmic levels of NFκB p65 were evaluated after cellular fractionation by Western blotting. We report that p62 is up-regulated in RPE cells under H2O2-induced oxidative stress and promotes autophagic activity. Depletion of endogenous p62 reduces autophagy by downregulation of ATG10 rendering RPE more susceptible to oxidative damage. NFκB p65 phosphorylation at Ser-536 was found to be critical for p62 upregulation in response to oxidative stress. Proteasome inhibition by H2O2 causes p62-NFκB signaling as antioxidant pre-treatment reversed p62 expression and p65 phosphorylation when RPE was challenged by H2O2 but not when by Lactacystin. p62 protein but not RNA levels are elevated in APOE4-HFC AMD mouse model, suggesting reduction of autophagic flux in disease conditions. Our findings suggest that p62 is necessary for RPE cytoprotection under oxidative stress and functions, in part, by modulating ATG10 expression. NFκB p65 activity may be a critical upstream initiator of p62 expression in RPE cells under oxidative stress.