Nowadays intravitreal drug injection is the most frequent treatment for retinal diseases. Despite widely use endophthalmitis is already most feared complication of every intravitreal injection in each patient. In clinical setting topical antibiotics have been widely used as a precaution to prevent endophthalmitis however recent published evidence showed it to be unnecessary. Furthermore repeated use of topical antibiotics might give rise to antibiotic resistance in conjunctival flora and thus more aggressive endophthalmitis. Strict asepsis has been awarded as the main rule for endophthalmitis prophylaxis intravitreal injection.
To make an account of published implant-related complications (IRC) by a systematic review of the literature.
A systematic search of Pubmed and Scopus databases and Google Scholar engine was performed with selection criteria to detect papers on IRC. We excluded unrelated papers and reviewed selected ones. We considered papers that did not explicitly state about occurrence or not occurrence of IRC as non-IRC reporting. Main outcome measures were the number of papers reporting on complications, IRC, and types of IRC.
After the search, selection, and addition, we studied 109 papers. Incidence of IRC was 4.5%, half required explantation. While 26 implant studies found IRCs (23%), 13 case reports on surgical complications, 8 (61.5%) of them reported IRC. Frequent complications were conjunctival erosion, blockage of the tube, migration to anterior chamber or damage to surrounding tissues.
Most papers did not report on IRC. Length or nature of studies may skew finding IRC. The incidence of IRC was 4.5%. Hard and sharp implants carry a greater risk of IRC and explantation.
The liver is the most common site of uveal melanoma (UM) metastasis with approximately 50% of UM patients being affected. With no proven therapies that mitigate metastases the mortality rate is 85% within the first year after detection of the liver disease. In this study, we provide a mechanistic understanding of the de-regulation of the TP53-MDM2 pathway in UM, which plays a central role in tumor biology.
We investigated the TP53-MDM2 signaling pathway in the microenvironment of liver metastases taken from both a murine orthotopic xenograft and post-mortem metastatic UM human liver. These findings were studied in-depth using both primary and metastatic UM cell lines treated with the MDM2 antagonist Nutlin-3a and the sirtuin inhibitor and transcriptional activator of TP53, Tenovin-6.
De-regulation of the TP53-MDM2 signaling pathway is specific to the liver microenvironment, providing a survival mechanism for UM metastases. Tenovin-6, not Nutlin-3a, reduced UM cell survival by increasing the percentage of cell death and reducing the percentage of proliferating cells. Tenovin-6 increased acetylation of p53, reduced ubiquitination of the protein, and acted as a cell cycle regulator.
Our findings suggest that in patients with metastatic UM de-regulation of TP53-MDM2 signaling pathway promotes growth of the liver metastases and provides pre-clinical information on the potential of targeting of the TP53-MDM2 signaling pathway via Tenovin-6.