Unexplained Vision Loss Associated With Intraocular Silicone Oil Tamponade in Rhegmatogenous Retinal Detachment Repair.

Purpose: To evaluate the visual outcomes with unexplained vision loss during or after silicone oil (SO) tamponade. Methods: This multicenter retrospective case series comprised patients with unexplained vision loss associated with SO tamponade or its removal. Eyes with other clear secondary identifiable causes of vision loss were excluded. Results: Twenty-nine eyes of 28 patients (64% male) were identified. The mean age was 50 ± 13 years (range, 13-78 years). The mean duration of SO tamponade was 148 ± 38 days. Eighteen eyes (62%) developed unexplained vision loss while under SO; 11 (38%) had vision loss after SO removal. The most common optical coherence tomography (OCT) finding was ganglion cell layer (GCL) thinning (55%). Eyes with vision loss after SO removal had a mean logMAR best-corrected visual acuity (BCVA) of 0.6 ± 0.7 (Snellen 20/85) before SO tamponade and 1.2 ± 0.4 (20/340) before SO removal. By the last follow-up after SO removal, the BCVA had improved to 1.1 ± 0.4 (20/235). In eyes with vision loss after SO removal, the BCVA before SO removal was 0.7 ± 0.7 (20/104), which deteriorated to 1.4 ± 0.4 (20/458) 1 month after SO removal. By the last follow-up, the BCVA had improved to 1.0 ± 0.5 (20/219). Conclusions: Unexplained vision loss can occur during SO tamponade or after SO removal. Vision loss was associated with 1000-centistoke and 5000-centistoke oil and occurred in macula-off and macula-on retinal detachments. The duration of tamponade was 3 months or longer in the majority of eyes. Most eyes had GCL thinning on OCT. Gradual visual recovery can occur yet is often incomplete.

Complete and Early Vitrectomy for Endophthalmitis After Cataract Surgery: An Alternative Treatment Paradigm.

PURPOSE: In this study, we report the treatment outcomes of complete and early vitrectomy for endophthalmitis (CEVE) after cataract surgery as the predominate initial treatment, accompanied by systemic antibiotics and retreatment of persistent or recurrent purulence (CEVE+). PATIENTS AND METHODS: Clinical features and microbiological factors were retrospectively reviewed in 62 eyes of 62 patients who were treated for acute postcataract endophthalmitis (APCE) occurring within three weeks of cataract surgery at Retina Specialists of Alabama, between 2007 and 2017. RESULTS: Visual acuity on presentation included light perception (LP) in 18 eyes (29%) and hand motion (HM) in 23 eyes (37%). Initial treatment was maximum possible vitrectomy in 48 eyes (77%) and tap-and-inject in 14 eyes (23%), with 38 eyes (61%) receiving two or more treatments. Cultures for the first intervention were positive in 49 eyes (79%) and virulent in 18 eyes (29%). At a median follow-up time of five months, final visual acuity was ≥20/40 in 49 eyes (79%), between 20/50 and 5/200 in seven eyes (11%), and <5/200 in six eyes (10%). Virulence was the strongest predictor of poor visual outcome. Retinal detachment occurred in four eyes (6%), likely from necrotic retinal defects in each case. CONCLUSION: Complete and early vitrectomy is a safe and effective initial treatment for APCE. When accompanied by systemic antibiotics and retreatment (CEVE+) of recurrent media opacification, it improves recovery of 20/40 or better visual acuity by approximately 50% compared to a predominantly tap-and-inject treatment paradigm. We recommend CEVE for fundus-obscuring APCE (~75% of all cases) whenever the view is inadequate to rule out macular distress.

miR-17-3p Exacerbates Oxidative Damage in Human Retinal Pigment Epithelial Cells.

Oxidative stress has been shown to contribute to the development of age-related macular degeneration (AMD). MicroRNAs (miRNA) are small non-coding RNA molecules that function in RNA silencing and post-transcriptional regulation of gene expression. We showed miR-17-3p to be elevated in macular RPE cells from AMD patients and in ARPE-19 cells under oxidative stress. Transfection of miR-17-3p mimic in ARPE-19 induced cell death and exacerbated oxidative lethality that was alleviated by miR-17-3p inhibitor. The expression of antioxidant enzymes manganese superoxide dismutase (MnSOD) and thioredoxin reductase-2 (TrxR2) were suppressed by miR-17-3p mimic and reversed by miR-17-3p inhibitor. These results suggest miR-17-3p aggravates oxidative damage-induced cell death in human RPE cells, while miR-17-3p inhibitor acts as a potential protector against oxidative stress by regulating the expression of antioxidant enzymes.

A Novel ImageJ Macro for Automated Cell Death Quantitation in the Retina.

PURPOSE: TUNEL assay is widely used to evaluate cell death. Quantification of TUNEL-positive (TUNEL+) cells in tissue sections is usually performed manually, ideally by two masked observers. This process is time consuming, prone to measurement errors, and not entirely reproducible. In this paper, we describe an automated quantification approach to address these difficulties. METHODS: We developed an ImageJ macro to quantitate cell death by TUNEL assay in retinal cross-section images. The script was coded using IJ1 programming language. To validate this tool, we selected a dataset of TUNEL assay digital images, calculated layer area and cell count manually (done by two observers), and compared measurements between observers and macro results. RESULTS: The automated macro segmented outer nuclear layer (ONL) and inner nuclear layer (INL) successfully. Automated TUNEL+ cell counts were in-between counts of inexperienced and experienced observers. The intraobserver coefficient of variation (COV) ranged from 13.09% to 25.20%. The COV between both observers was 51.11 ± 25.83% for the ONL and 56.07 ± 24.03% for the INL. Comparing observers' results with macro results, COV was 23.37 ± 15.97% for the ONL and 23.44 ± 18.56% for the INL. CONCLUSIONS: We developed and validated an ImageJ macro that can be used as an accurate and precise quantitative tool for retina researchers to achieve repeatable, unbiased, fast, and accurate cell death quantitation. We believe that this standardized measurement tool could be advantageous to compare results across different research groups, as it is freely available as open source.

Mitochondrial DNA has a pro-inflammatory role in AMD.

Age-related macular degeneration (AMD) is the leading cause of irreversible blindness in the elderly of industrialized nations, and there is increasing evidence to support a role for chronic inflammation in its pathogenesis. Mitochondrial DNA (mtDNA) has been recently reported to be pro-inflammatory in various diseases such as Alzheimer's and heart failure. Here, we report that intracellular mtDNA induces ARPE-19 cells to secrete inflammatory cytokines IL-6 and IL-8, which have been consistently associated with AMD onset and progression. The induction was dependent on the size of mtDNA, but not on specific sequence. Oxidative stress plays a major role in the development of AMD, and our findings indicate that mtDNA induces IL-6 and IL-8 more potently when oxidized. Cytokine induction was mediated by STING (Stimulator of Interferon Genes) and NF-κB as evidenced by abrogation of the cytokine response with the use of specific inhibitors (siRNA and BAY 11-7082, respectively). Finally, mtDNA primed the NLRP3 inflammasome. This study contributes to our understanding of the potential pro-inflammatory role of mtDNA in the pathogenesis of AMD.

Cholesterol crystals induce inflammatory cytokines expression in a human retinal pigment epithelium cell line by activating the NF-κB pathway.

PURPOSE: To investigate the expression of inflammatory cytokines in ARPE-19 cells after stimulation with cholesterol crystals. METHODS: APRE-19 cells were cultured, primed with IL-1α, and treated with cholesterol crystals under different concentrations. Inflammatory cytokines (mature-IL-1ß, IL-6, and IL-8) in supernatant and inflammatory cytokines (pro-IL-1ß, IL-18) in cell lysate were detected by western blot. The NF-κB pathway inhibitor BAY 11-7082 was used to determine the pathway of cytokine expression. RESULTS: Cholesterol crystals did not induce the nucleotide-binding domain leucine-rich repeat containing family, pyrin domain containing 3 (NLRP3) inflammasome, but did increase pro-IL-1ß expression in ARPE-19 cells. Cholesterol crystals increased pro-IL-1ß expression by activating the NF-κB pathway. Cholesterol crystal activation of the NF-κB pathway also leads to increased IL-6 and IL-8 expression. CONCLUSION: Cholesterol crystals can induce inflammatory cytokine expression in ARPE-19 cells by activating the NF-κB pathway.