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Purpose: To describe a single case of systemic lymphoma recurring in the iris and ciliary body. Methods: A retrospective case review was performed. Results: A 75-year-old woman presented to the retina service with an iris mass in the left eye. Her medical history was significant for previous systemic diffuse large B-cell lymphoma treated with systemic chemotherapy. Aqueous sampling was significant for recurrence of the disease. Local therapy with intravitreal (IVT) methotrexate was initiated. Although there was initial improvement, an increased interval between injections led to disease recurrence. External beam radiation to the left eye was then applied, leading to a complete clinical remission. Conclusions: Systemic lymphoma presenting in the iris is a rare manifestation that should be considered on the differential for an amelanotic iris lesion. Although monotherapy with IVT methotrexate did not control the ocular disease in this patient, subsequent external beam radiation resulted in complete clinical remission., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of the article., (© The Author(s) 2024.)

Purpose: To evaluate the visual outcomes and complications with a polytetrafluoroethylene (Gore-Tex)-fixated intraocular lens (IOL) (Akreos AO60, Bausch + Lomb). Methods: Eyes with inadequate capsule support for in-the-bag IOL implantation had pars plana vitrectomy (PPV) and IOL placement at a single center. The main outcome measures were the postoperative visual acuity (VA) and complication rates. Results: During the study, 783 surgeries were performed. The mean visual acuity gain was 28.5 Early Treatment Diabetic Retinopathy Study letters ( P < .01), with a mean time to best VA of 3.05 months. Statistical hypotony (intraocular pressure <6.5 mm Hg) was present in 214 cases (27.3%), and clinical features of hypotony were present in 46 cases. Five percent of the complications were directly related to the IOL. There were 3 cases of IOL opacification, 2 with silicone oil endotamponade and 1 with perfluoropropane endotamponade. Conclusions: PPV with Akreos IOL implantation was an effective technique for secondary IOL placement. Complications directly related to the IOL were uncommon., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of the article., (© The Author(s) 2024.)

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., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2023.)

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.

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.]., (Copyright 2021, SLACK Incorporated.)

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.

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-1β, 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-1β, 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-1β, 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., (© 2018 Royal Australian and New Zealand College of Ophthalmologists.)

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.

Partial-thickness folds of the inner retina and outer retina, as well as full-thickness retinal folds, may occur after the repair of rhegmatogenous retinal detachment. Although these can look similar on clinical examination, imaging with optical coherence tomography facilitates differentiation. With optical coherence tomography analysis, inner retinal folds exhibit corrugations of the inner retina while outer retinal folds display hyperreflective lesions located just above the retinal pigment epithelium that may extend into the outer nuclear layer. In the case of a classic full-thickness retinal fold, all layers of the neurosensory retina may separate together from the retinal pigment epithelium with retinal reduplication and base-to-base photoreceptor orientation. We review the pathogenesis, risk factors, prevention, and management options of retinal folds. As the terminology for retinal folds is diverse, we highlight optical coherence tomography-based descriptions for retinal folds that have been used in the literature. Factors predicting visual recovery, mechanisms of spontaneous fold regression, and the effect of internal limiting membrane peeling on the incidence of folds are potential areas of future study., (Copyright © 2018 Elsevier Inc. All rights reserved.)

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-1β, IL-10, IL-12p70, IL-33, interferon (IFN)-γ, IFN-α, IFN-β, 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., (Crown Copyright © 2017. Published by Elsevier Inc. All rights reserved.)

Susac syndrome is characterized by encephalopathy, sensorineural hearing loss, and branch retinal artery occlusion. Additional ocular findings include arteriolar wall hyperfluorescence and Gass plaques. We present a 51-year-old Caucasian woman with ophthalmologic findings indicative of Susac syndrome in the setting of tinnitus and migraine with aura.

As an approved vaccine adjuvant for use in humans, alum has vast health implications, but, as it is a crystal, questions remain regarding its mechanism. Furthermore, little is known about the target cells, receptors, and signaling pathways engaged by alum. Here we report that, independent of inflammasome and membrane proteins, alum binds dendritic cell (DC) plasma membrane lipids with substantial force. Subsequent lipid sorting activates an abortive phagocytic response that leads to antigen uptake. Such activated DCs, without further association with alum, show high affinity and stable binding with CD4(+) T cells via the adhesion molecules intercellular adhesion molecule-1 (ICAM-1) and lymphocyte function-associated antigen-1 (LFA-1). We propose that alum triggers DC responses by altering membrane lipid structures. This study therefore suggests an unexpected mechanism for how this crystalline structure interacts with the immune system and how the DC plasma membrane may behave as a general sensor for solid structures.

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.

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., (Copyright © 2010 Elsevier B.V. All rights reserved.)

Inflammation significantly contributes to the progression of chronic kidney disease (CKD). Inflammasome-dependent cytokines, such as IL-1β 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-1β, 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-1β 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.

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., (Copyright (c) 2010 AGA Institute. Published by Elsevier Inc. All rights reserved.)