Incidence and Risk Factors for Delayed Retinal Tears after an Acute, Symptomatic Posterior Vitreous Detachment.

PURPOSE: To determine the long-term incidence of and risk factors for delayed retinal tears after acute, symptomatic posterior vitreous detachment (PVD) without concurrent retinal tears. DESIGN: Retrospective, observational case series. SUBJECTS: Patients diagnosed with an acute, symptomatic PVD without concurrent retinal tears at a tertiary eye center between 2013 and 2018. METHODS: This is a retrospective, consecutive, and observational case series. Acute and symptomatic PVD was defined as experiencing flashes or floaters for 1 month or less at the time of diagnosis. Patients with a retinal tear or detachment at or before the time of diagnosis were not included. The occurrence and timing of subsequent retinal tears after initial PVD diagnosis were recorded. The age, sex, race, refractive error, lens status, lattice degeneration status, and type of physician (retina specialist vs. nonretina specialist) who saw the patient were also recorded. MAIN OUTCOME MEASURES: Time to the development of a delayed retinal tear. RESULTS: A total of 389 eyes from 389 patients had acute and symptomatic PVDs without concurrent retinal tears or detachments at diagnosis. Kaplan-Meier analysis showed that 7.39% of eyes developed delayed retinal tears by 6.24 years after initial PVD diagnosis. Of these tears, 50% occurred within 4.63 months of PVD diagnosis, and 63.46% occurred within 1 year of PVD diagnosis. Cox-Mantel log-rank analysis showed that those who were younger (age < 60 years), myopic, or had lattice degeneration were more likely to develop tears. A multivariate Cox proportional-hazards models controlling for other significant risk factors supported lattice degeneration as a likely risk factor for delayed retinal tear. CONCLUSIONS: This study demonstrates that 7.39% of patients with acute, symptomatic PVD without concurrent retinal tears develop delayed retinal tears by 6.24 years after PVD diagnosis, with many developing tears well after a typical 6-week follow-up time for PVD. Lattice degeneration is a significant risk factor for delayed tears. These findings can guide clinicians in establishing optimal follow-up protocols for patients with acute, symptomatic PVD. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

The Role of Retinal Pigment Epithelial Cells in Regulation of Macrophages/Microglial Cells in Retinal Immunobiology.

The ocular tissue microenvironment is immune privileged and uses several mechanisms of immunosuppression to prevent the induction of inflammation. Besides being a blood-barrier and source of photoreceptor nutrients, the retinal pigment epithelial cells (RPE) regulate the activity of immune cells within the retina. These mechanisms involve the expression of immunomodulating molecules that make macrophages and microglial cells suppress inflammation and promote immune tolerance. The RPE have an important role in ocular immune privilege to regulate the behavior of immune cells within the retina. Reviewed is the current understanding of how RPE mediate this regulation and the changes seen under pathological conditions.

High-fat diet aggravates islet beta-cell toxicity in mice treated with clozapine.

BACKGROUND: Clozapine, an atypical antipsychotic drug, induces derangements in glucose homeostasis in certain patients. This study investigated the mechanisms of clozapine-induced beta-cell toxicity. METHODS: Fifty-two healthy C57BL/6 male mice were randomized into 4 groups to study the effects of clozapine (group C, D) and a high-fat diet (group B, D). Three mice from each group were randomly selected to determine the amount of food intake on days 8-10, and their pancreases were removed for histological examination on day 11. The remaining 10 mice in each group were sacrificed at the 8th week to measure pancreatic insulin content (PIC). RESULTS: Mice given clozapine for 8 weeks demonstrated trends of lower PIC. The histological examination of the pancreases retrieved on day 11 already revealed apoptotic changes and suppression of cell proliferation. Although mice fed high-fat chow gained weight, mice given both clozapine and a high-fat diet showed less weight gain and more severe histological deterioration, and had the lowest PIC levels of the 4 groups. CONCLUSION: Pancreatic beta-cell apoptosis, suppression of cell proliferation, and trends of reduction in pancreatic insulin content were observed in mice taking clozapine. The findings of clozapine induced beta-cell toxicity were further aggravated when mice were concomitantly fed a high-fat diet.

Synergistic Effect of Hyperglycemia and p27(kip1) Suppression on Adult Mouse Islet Beta Cell Replication.

The complementary role of hyperglycemia and p27(kip1) suppression on islet beta cell regeneration was investigated in a syngeneic mouse model. p27(kip1) gene silencing was performed by infecting islets of C57BL/6 with shRNA lentiviral particles. At 54 hours after viral infection, p27(kip1) protein content in cultured targeting islets was 22% of that in freshly isolated islets. Six days after transplantation to diabetic mice, targeting islet graft had considerably more cells with Ki67-staining nuclei than nontargeting islets. The mice in the targeting-islet group had a significantly shorter duration of temporary hyperglycaemia than mice in the non-targeting-islet group. The long-term ex vivo beneficial effect of p27(kip1) silencing on graft function was also indicated by the significantly higher cumulative cure rate for diabetes in mice receiving 200 targeting islets than that in mice receiving 200 non-targeting islets. Our data suggest that hyperglycemia and persistent p27(kip1) suppression have a synergistic effect on islet beta cell replication in adult mice.