Effect of Macular Internal Limiting Membrane Peeling on Single Surgery Success Rates of Vitrectomy for Uncomplicated, Primary Macula-Off Retinal Detachment.

Purpose: To determine the anatomic and visual outcomes of pars plana vitrectomy for uncomplicated, primary macula-off rhegmatogenous retinal detachment (RRD) with and without internal limiting membrane (ILM) peeling. Methods: This retrospective chart review comprised 129 patients with uncomplicated, primary macula-off RRD presenting between January 1, 2016, and May 31, 2021. Thirty-six patients (27.9%) had ILM peeling and 93 (72.0%) did not. The primary outcome was the rate of recurrent RRD. Secondary outcomes included preoperative and postoperative best-corrected visual acuity (BCVA), epiretinal membrane (ERM) formation, and macular thickness. Results: No significant difference was found in the risk for recurrent RRD between patients who had ILM peeling and those who did not (2.8% [1/36] and 5.4% [5/93], respectively) (P = 1.00). The final postoperative BCVA was better in eyes that did not have ILM peeling (P< .001). No ERM occurred in the group with ILM peeling, whereas ERM occurred in 27 patients (29.0%) who did not have ILM peeling. The temporal macular retina was thinner in eyes in which ILM peeling was performed. Conclusions: The risk for recurrent RRD was not statistically lower in eyes having ILM peeling of the macula in uncomplicated, primary macula-off RRD. Despite a reduction in postoperative ERM formation, eyes having macular ILM peeling had worse postoperative VA.

Cilioretinal Artery Occlusion in Posterior Scleritis Secondary to Ankylosing Spondylitis.

The authors describe the case of a 25-year-old male who presented with a cilioretinal artery occlusion secondary to posterior scleritis. The patient had a history of juvenile spondyloarthritis that evolved into ankylosing spondylitis. Cilioretinal artery occlusion is a rare complication of posterior scleritis, having only been described once previously in the literature. This is the first reported case of a cilioretinal artery occlusion in posterior scleritis that was associated with an underlying systemic disease. [Ophthalmic Surg Lasers Imaging Retina. 2021;52:102-106.].

Pneumatic Vitreolysis With Intravitreal Air for Focal Vitreomacular Traction.

Purpose: To determine whether pneumatic vitreolysis with intravitreal air is effective for focal vitreomacular traction (VMT). Methods: We conducted a retrospective consecutive case series of 20 eyes from 19 individuals with focal VMT who underwent pneumatic vitreolysis with intravitreal air (January 2017 to November 2018). We analyzed patients via spectral-domain optical coherence tomography before intravitreal air injection and at 1 month. The primary outcome measure was release of VMT. Results: We observed release of VMT in 55% of individuals. An analysis limited to phakic eyes demonstrated release of VMT in 69%, and 65% developed improved best-corrected visual acuity. Individuals with persistent VMT and visual improvement had a significant reduction in angle of vitreoretinal insertion (P < .01), area under VMT (P < .05), and subfoveal cyst area (P < .05). Conclusions: Intravitreal air is an effective treatment for focal VMT. In individuals with persistent VMT, visual-acuity improvement was associated with a reduction in overall VMT.

PHACOVITRECTOMY FOR PRIMARY RHEGMATOGENOUS RETINAL DETACHMENT REPAIR: A Retrospective Review.

PURPOSE: To analyze the single surgery success rate and anterior segment complications related to phacoemulsification and intraocular lens implantation in a series of patients undergoing phacovitrectomy for all types of primary rhegmatogenous retinal detachment. METHODS: We performed a retrospective interventional case series on 302 eyes undergoing phacovitrectomy for primary rhegmatogenous retinal detachment repair between November 1, 2016, and February 2, 2019, in Edmonton, Canada. Primary outcomes included single surgery retinal reattachment rate and anterior segment complications. Secondary outcomes included the effects of proliferative vitreoretinopathy and macula and/or peripheral internal limiting membrane peeling on the rate of surgical success. RESULTS: The single surgery success rate of phacovitrectomy for all types of primary rhegmatogenous retinal detachment was 85.1%. The presence of proliferative vitreoretinopathy was associated with lower surgical success (odds ratio, 0.33; P = 0.01). Macular internal limiting membrane peeling was associated with higher surgical success (odds ratio, 2.4; P = 0.05). Anterior segment complications included posterior capsular opacification (28.8%), posterior synechiae (10.9%), and posterior capsular rupture (2.3%). CONCLUSION: Phacovitrectomy is a safe and effective treatment option for the primary repair of rhegmatogenous retinal detachments. This study provides evidence to support the safe incorporation of phacoemulsification and intraocular lens implantation with retinal surgery.

NOVEL PATIENT POSITIONING APPARATUS FOR RETINAL SURGERY IN A CASE OF SEVERE KYPHOSIS.

PURPOSE: To describe a novel patient positioning apparatus for intraocular surgery capable of accommodating patients with thoracic kyphosis. METHODS: Case report. RESULTS: A 60-year-old man presented with a macula-off retinal detachment and severe ankylosing spondylitis. The patient was scheduled for combined pars plana vitrectomy and scleral buckle. Because of the patient's severe kyphosis, a custom-designed positioning apparatus was built. The setup involved a canvas with 10 sewn-on straps and a Skytron operating table with strap inserts. Padding and blankets were also used to secure the patient comfortably in the Trendelenburg position. Surgery was uncomplicated and retinal detachment repair was successfully performed. CONCLUSION: To the authors' knowledge, this is the first report detailing a vest-like support apparatus for patients with thoracic kyphosis used in vitreoretinal surgery. This apparatus can be prepared using any conventional operating table, and it offers an effective approach to intraocular surgery for patients who cannot lie flat.

MASSIVE SUBRETINAL GAS AFTER VITRECTOMY SURGERY: MECHANISM AND MANAGEMENT.

PURPOSE: To describe the complication of subretinal gas after pars plana vitrectomy for rhegmatogenous retinal detachment, as well as its management. METHODS: The presence of subretinal gas was noted on postoperative Day 1 after pars plana vitrectomy for a chronic rhegmatogenous retinal detachment. Resolution of subretinal gas was facilitated by an infusion line and external sclerotomy to expand the vitreous cavity. Residual subretinal gas was removed through a posterior retinotomy after fluid-air exchange. RESULTS: This technique resulted in the successful evacuation of subretinal gas, allowing for chorioretinal adhesion and reattachment of the retina. CONCLUSION: Subretinal gas can rarely occur after pars plana vitrectomy for rhegmatogenous retinal detachment. This complication can be successfully managed by way of external drainage, followed by evacuation of residual gas through fluid-air exchange and posterior retinotomy.

Effects of intravitreal bevacizumab in Gram-positive and Gram-negative models of ocular inflammation.

BACKGROUND: Exogenous endophthalmitis is a potential complication of intraocular surgery and frequently results in visual impairment. Current treatment involves administration of intravitreal (IVT) antibiotics with or without vitrectomy surgery. Evidence for the use of adjunctive anti-inflammatory agents is conflicting. We set out to determine if bevacizumab, a humanized monoclonal IgG1 antibody targeted against vascular endothelial growth factor (VEGF), has anti-inflammatory properties in experimental models of Gram-positive and Gram-negative inflammation. METHODS: BALB/c mice were subjected to lipopolysaccharide- (LPS) or peptidoglycan- (PGN) induced ocular inflammation and treated with IVT bevacizumab. Iris microvasculature was imaged 6 hours following irritant/treatment using intravital microscopy (IVM) before the mice were euthanized and the eyes were enucleated immediately post-mortem. Following enucleation, levels of VEGF and 23 cytokines and chemokines (IL-1α, IL-1ß, IL-2, IL-3, IL-4, IL-5, IL-6, IL-10, IL-12 (p40), IL-12 (p70), IL-13, IL-17, TNF, KC, G-CSF, GM-CSF, Eotaxin, INF-γ, MCP-1, MIP-1α, MIP-1ß, RANTES) were quantified using a multiplex assay. RESULTS: Levels of VEGF were significantly increased during the inflammatory response, triggered by either PGN or LPS. Both the adherence of leukocytes to the iris vascular endothelium and the levels of pro-inflammatory cytokines and chemokines were significantly increased following administration of either irritant. Treatment with bevacizumab decreased levels of leukocyte adherence in LPS-treated eyes, however, not in PGN-treated eyes. Conversely, bevacizumab treatment decreased levels of cytokines and chemokines (TNF, IL-6, MCP-1, MIP-1α, MIP-1ß, RANTES, KC) in PGN-treated eyes, however, not in LPS-treated eyes. CONCLUSIONS: Within a 6-hour window bevacizumab had anti-inflammatory actions that were distinct in both Gram-positive (PIU) and Gram-negative (EIU) models, respectively. Given our findings, this would suggest that bevacizumab may have utility as an adjunctive therapy to IVT antibiotics and vitrectomy in the management of exogenous endophthalmitis.

VEGF-A is increased in exogenous endophthalmitis.

OBJECTIVE: Exogenous endophthalmitis is an ophthalmologic emergency defined by panocular inflammation. Vascular endothelial growth factor A (VEGF-A) contributes to inflammation by promoting chemotaxis of monocytes and granulocytes and by increasing vascular permeability. The purpose of this article is to determine if VEGF-A is elevated in the vitreous samples obtained from individuals with exogenous endophthalmitis. METHODS: Vitreous samples from individuals with exogenous endophthalmitis (n = 18) were analyzed via Luminex assay and enzyme-linked immunosorbent assay for the cytokines VEGF-A, tumor necrosis factor (TNF), interleukin 6 (IL-6), IL-8 (chemokine [CXCL]-8), IL-1ß, IL-10, IL-12p70, IL-33, interferon (IFN)-γ, IFN-α, IFN-ß, chemokine ligand (CCL)-3, IL-2, IL-5, IL-15, CXCL-10, CCL-2, IL-1Ra, CCL-5, IL-17, and CCL-11. Vitreous samples obtained at the time of macular hole surgery served as controls (n = 8). RESULTS: Concentrations of VEGF-A were significantly elevated in vitreous samples from individuals with exogenous endophthalmitis compared with macular hole (p < 0.001). VEGF-A was significantly upregulated in individuals with exogenous endophthalmitis after cataract surgery (p = 0.001), vitrectomy (p = 0.024), and intravitreal injection (p = 0.012). VEGF-A concentrations were similar in both culture-positive and culture-negative populations (p > 0.05). In a linear regression model, levels of VEGF-A correlated significantly with the chemokine CXCL-8 (p = 0.028). CONCLUSIONS: We demonstrate that VEGF-A is potently upregulated in exogenous endophthalmitis. This observation provides a foundation for future studies of targeted VEGF-A blockade in the management of endophthalmitis.

Anti-BK virus mechanisms of sirolimus and leflunomide alone and in combination: toward a new therapy for BK virus infection.

BACKGROUND: Human BK polyomavirus is the causative agent of BK nephropathy which is now the leading cause of early renal graft loss. Although no randomized clinical trials have supported this therapy, reduction of immunosuppressive drugs is the current BK nephropathy treatment. We hypothesized that inhibition of the intracellular protein kinase pathways activated by BK virus may be a more effective therapeutic strategy than reduction of immunosuppression. METHODS AND RESULTS: Four days after infection of renal epithelial cells lines CCD1103, CCD1105 and human primary tubular epithelial cells with BK virus, we found increased phosphorylation of 3'-phosphoinositide-dependent kinase-1 (PDK-1), the protein kinase Akt (Akt), mammalian target of rapamycin (mTOR), and 70 kDa ribosomal protein S6 kinase (p70S6K). To inhibit this pathway, we used sirolimus, which repressed p70S6K phosphorylation and reduced BK virus large T antigen expression in a dose-dependent manner. We then used the tyrosine kinase inhibitor leflunomide (using the active metabolite A77 1726), which decreased PDK1 and Akt phosphorylation and inhibited BK virus genome replication and early gene expression. The combination of sirolimus and leflunomide inhibited BK virus genome replication, large T antigen expression, PDK1, Akt, mammalian target of rapamycin, and p70S6K phosphorylation. CONCLUSIONS: On the basis of these results, we suggest that inhibition of protein kinase pathways with a combination of sirolimus and leflunomide may be an effective therapy for BK virus reactivation. Because both sirolimus and leflunomide possess immunosuppressive activity, combination therapy may reduce BK pathogenesis while maintaining appropriate transplant immunosuppression.

MAP kinase activation increases BK polyomavirus replication and facilitates viral propagation in vitro.

BK polyomavirus causes disease in immunosuppressed patients. BK virus replication was augmented in HEL-299 cells cultured in conditions that activated the MAP kinase, ERK1/2. To determine if MAP kinase activation increased BK virus replication, cells were treated with serum and phorbol 12-myristate 13-acetate (PMA). Serum and PMA stimulated large T-antigen expression and increased BK virus DNA replication. The effects of serum/PMA were directly related to MAP kinase signal activation since viral replication was reduced by the MEK1/2 inhibitor U0126. PMA also increased cyclin D1 expression and inhibition of cyclin D1/CDK4 complex and the cell cycle reduced BK virus infection. The PMA effect occurred independent of direct transcriptional activation of the viral NCCR. In HEL-299 cells, virus infection in high serum and PMA accelerated viral replication that resulted, within 7 days, in the production of high titer infectious BK virus. These results show that MAP kinase signal activation increases BK virus replication.

The NLRP3 inflammasome promotes renal inflammation and contributes to CKD.

Inflammation significantly contributes to the progression of chronic kidney disease (CKD). Inflammasome-dependent cytokines, such as IL-1ß and IL-18, play a role in CKD, but their regulation during renal injury is unknown. Here, we analyzed the processing of caspase-1, IL-1ß, and IL-18 after unilateral ureteral obstruction (UUO) in mice, which suggested activation of the Nlrp3 inflammasome during renal injury. Compared with wild-type mice, Nlrp3(-/-) mice had less tubular injury, inflammation, and fibrosis after UUO, associated with a reduction in caspase-1 activation and maturation of IL-1ß and IL-18; these data confirm that the Nlrp3 inflammasome upregulates these cytokines in the kidney during injury. Bone marrow chimeras revealed that Nlrp3 mediates the injurious/inflammatory processes in both hematopoietic and nonhematopoietic cellular compartments. In tissue from human renal biopsies, a wide variety of nondiabetic kidney diseases exhibited increased expression of NLRP3 mRNA, which correlated with renal function. Taken together, these results strongly support a role for NLRP3 in renal injury and identify the inflammasome as a possible therapeutic target in the treatment of patients with progressive CKD.

Clostridium difficile toxin-induced inflammation and intestinal injury are mediated by the inflammasome.

BACKGROUND & AIMS: Clostridium difficile-associated disease (CDAD) is the leading cause of nosocomial diarrhea in the United States. C difficile toxins TcdA and TcdB breach the intestinal barrier and trigger mucosal inflammation and intestinal damage. The inflammasome is an intracellular danger sensor of the innate immune system. In the present study, we hypothesize that TcdA and TcdB trigger inflammasome-dependent interleukin (IL)-1beta production, which contributes to the pathogenesis of CDAD. METHODS: Macrophages exposed to TcdA and TcdB were assessed for IL-1beta production, an indication of inflammasome activation. Macrophages deficient in components of the inflammasome were also assessed. Truncated/mutated forms of TcdB were assessed for their ability to activate the inflammasome. The role of inflammasome signaling in vivo was assessed in ASC-deficient and IL-1 receptor antagonist-treated mice. RESULTS: TcdA and TcdB triggered inflammasome activation and IL-1beta secretion in macrophages and human mucosal biopsy specimens. Deletion of Nlrp3 decreased, whereas deletion of ASC completely abolished, toxin-induced IL-1beta release. TcdB-induced IL-1beta release required recognition of the full-length toxin but not its enzymatic function. In vivo, deletion of ASC significantly reduced toxin-induced inflammation and damage, an effect that was mimicked by pretreatment with the IL-1 receptor antagonist anakinra. CONCLUSIONS: TcdA and TcdB trigger IL-1beta release by activating an ASC-containing inflammasome, a response that contributes to toxin-induced inflammation and damage in vivo. Pretreating mice with the IL-1 receptor antagonist anakinra afforded the same level of protection that was observed in ASC-/- mice. These data suggest that targeting inflammasome or IL-1beta signaling may represent new therapeutic targets in the treatment of CDAD.