Repeated Topical Administration of 3 nm Cerium Oxide Nanoparticles Reverts Disease Atrophic Phenotype and Arrests Neovascular Degeneration in AMD Mouse Models.

Increased oxidative stress in the retina and retinal pigment epithelium is implicated in age-related macular degeneration (AMD). Antioxidant cerium oxide nanoparticles (CeO2NPs) have been used to treat degenerative retinal pathologies in animal models, although their delivery route is not ideal for chronic patient treatment. In this work, we prepared a formulation for ocular topical delivery that contains small (3 nm), nonaggregated biocompatible CeO2NPs. In vitro results indicate the biocompatible and protective character of the CeO2NPs, reducing oxidative stress in ARPE19 cells and inhibiting neovascularization related to pathological angiogenesis in both HUVEC and in in vitro models of neovascular growth. In the in vivo experiments, we observed the capacity of CeO2NPs to reach the retina after topical delivery and a subsequent reversion of the altered retinal transcriptome of the retinal degenerative mouse model DKOrd8 toward that of healthy control mice, together with signs of decreased inflammation and arrest of degeneration. Furthermore, CeO2NP eye drops' treatment reduced laser-induced choroidal neovascular lesions in mice by lowering VEGF and increasing PEDF levels. These results indicate that CeO2NP eye drops are a beneficial antioxidant and neuroprotective treatment for both dry and wet forms of AMD disease.

Ex-Press P50 device filtering failure due to non-visible intraluminal blockages.

PURPOSE: To describe Ex-Press P50 failures due to an internal blockage. METHODS: A retrospective series of 248 eyes of 219 patients with Ex-Press P50 surgery was conducted. Of these cases, 18 (7.2%) required surgical revision due to filtration failure with no visible blockages in the gonioscopy and no filtering bleb in the slit lamp examination. In all of these cases, we found fibrosis on the edges of the scleral flap. After dissecting the scleral flap, filtration through the implant was restored spontaneously in 10 (4.0%) cases. In two cases fibrous tissue was observed on the tip of the implant and was necessary to remove it. In 6 (2.4%) cases, there was no filtration despite no visible obstruction and attempts to restore the flow were unsuccessful, requiring extraction of the implant and reconverting to trabeculectomy. Two of the removed devices were sanded until the lumen was visible to ascertain the nature of the obstruction. RESULTS: In our series, the most common cause of failure was episcleral fibrosis. In 2.4% of the cases, the blockage was intraluminal and aqueous flow could not be restored. CONCLUSION: In the Ex-Press P50 implant an internal blockage, that is not visible through the proximal or distal orifices, may be the cause of failure. Unblocking by surgical maneuvers is not feasible due to the intraluminal design. These cases can be solved by extraction of the implant and conversion to trabeculectomy.

In a randomized controlled trial, cataract surgery in both eyes increased benefits compared to surgery in one eye only.

BACKGROUND AND OBJECTIVE: Despite recommendation of surgery in both eyes in patients with bilateral cataract, there is little evidence about the benefits of second-eye surgery. The objective of this study was to compare the benefits of cataract surgery in both eyes with those of surgery in one eye only. STUDY DESIGN AND SETTING: Two-arm randomized controlled trial involving 296 patients with bilateral cataracts of two public teaching hospitals. Patients were randomly assigned to receive surgery in one eye only (control group) or surgery in both eyes, one eye at a time (intervention group). The main outcome measures were binocular visual acuity, binocular contrast sensitivity, stereopsis, and patient-reported visual disability (VF-14), measured 4-6 months postoperatively. RESULTS: A total of 135 (91.2%) and 139 (93.9%) patients completed the trial in the control and intervention groups, respectively. Postoperatively, intervention group presented a better visual acuity (difference of 0.07; 95% CI = 0.03, 0.12), stereopsis (0.62 log sec arc; 95% CI = 0.45, 0.79), and VF-14 (8.2 points; 95% CI = 4.4, 12.4). No significant differences were found for contrast sensitivity. CONCLUSIONS: Bilateral cataract patients should have surgery in both eyes. Including stereopsis and patient-reported visual disability in the assessment of cataract patients, especially after first-eye surgery, will improve the evaluation of effectiveness.

CD4-CD8 and CD28 expression in T cells infiltrating the vitreous fluid in patients with proliferative diabetic retinopathy: a flow cytometric analysis.

OBJECTIVES: To investigate CD4-CD8 and CD28 expression in T cells infiltrating the vitreous fluid in patients with proliferative diabetic retinopathy and to evaluate the relationship between the infiltrating T cells and both the activity of proliferative diabetic retinopathy and the clinical outcome. METHODS: Both vitreous and peripheral blood samples were obtained simultaneously from 20 consecutive diabetic patients and analyzed by flow cytometry. Three diabetic patients were excluded because there were no viable cells in the vitreous fluid. Six nondiabetic patients requiring vitrectomy were also studied. RESULTS: T lymphocytes were detected in all 6 diabetic patients with vitreous hemorrhage and in 6 (55%) of the 11 diabetic patients without vitreous hemorrhage, but in none of the nondiabetic patients. The percentages of T cells (CD3+), TCD4+ (CD3+ CD4+), and TCD8+ (CD3+ CD8+) subsets, as well as the expression of CD28, were similar in the vitreous fluid and in the peripheral blood in patients with vitreous hemorrhage. However, in patients without vitreous hemorrhage, the percentage of CD4+ CD28-T cells in the vitreous fluid was significantly higher than in the peripheral blood (33.34% [20.75%-100.00%] vs 8.45% [2.43%-56.59%]; P =.02). In addition, all of these patients showed quiescent retinopathy and their outcome was better than that of patients with vitreous hemorrhage and patients in whom intravitreous T cells were undetectable. CONCLUSION: T cells infiltrating the vitreous of diabetic patients without vitreous hemorrhage not only show a different pattern than in the peripheral blood but also seem to improve the prognosis of proliferative diabetic retinopathy. CLINICAL RELEVANCE: Our results provide further understanding of events involved in the autoimmune response in diabetic retinopathy and may aid in the research for new treatment approaches.