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Browsing by Author "Cantor, Louis B."
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Item A narrative review on the association of high intraocular pressure and glaucoma in patients with retinal vein occlusion(AME Publishing Company, 2022) Jabbehdari, Sayena; Yazdanpanah, Ghasem; Cantor, Louis B.; Hajrasouliha, Amir Reza; Ophthalmology, School of MedicineBackground and objective: Retinal vein occlusion (RVO) is a major cause of vision loss and elevated intraocular pressure (IOP), high ocular perfusion pressure, and glaucoma are known ophthalmic risk factors for RVO. The aim of this paper is to provide the update on the association and management of high IOP/glaucoma and RVO. Methods: A literature review was performed in PubMed and Medline until May 2022 utilizing specific keywords and cross-matched reference lists. Key content and findings: The association of RVO with high IOP/glaucoma may be attributed to retinal ganglion cell loss due to retinal ischemia in high IOP and glaucoma. As new modalities showed, decreased optic disc perfusion, reduced density of blood vessels in the optic nerve head of glaucoma patients, changes in the peripapillary microvascular parameters, and decreased retinal nerve fiber layer (RNFL) thickness of the optic nerve head of eyes with RVO suggest a common pathway between RVO and glaucoma. Literature suggests the close follow up for glaucoma development among patients with non-arteriovenous (AV) crossing (optic cup or optic nerve sited) RVO in fellow eye and management of elevated IOP among RVO cases treated with anti-vascular endothelial growth factor (VEGF) antibodies/corticosteroids and those with preexisting primary open angle glaucoma (POAG). Conclusions: Determining potential patient responses to treatment and considering therapeutic options are challenging among patients with RVO and glaucoma. However, IOP lowering managements in preventing IOP spikes in patients with preexisting glaucoma and early treatment of macular edema in eyes with RVO is recommended.Item The acute and chronic effects of intravitreal anti-vascular endothelial growth factor injections on intraocular pressure: A review(Elsevier, 2017) Bracha, Peter; Moore, Nicholas A.; Ciulla, Thomas A.; WuDunn, Darrell; Cantor, Louis B.; Department of Ophthalmology, School of MedicineThe acute and chronic effects of repeated intravitreal antivascular endothelial growth factor (VEGF) injections on intraocular pressure have not been fully characterized, and the development of sustained ocular hypertension could adversely affect patients who are at risk of glaucomatous optic neuropathy. As expected, volume-driven, acute ocular hypertension immediately follows intravitreal injection, but this pressure elevation is generally transient and well tolerated. Several medications have been investigated to limit acute ocular hypertension following anti-VEGF therapy, but the benefits of pretreatment are not conclusive. Chronic, sustained ocular hypertension, distinct from the short-term acute ocular hypertension after each injection, has also been associated with repeated intravitreal anti-VEGF injections. Risk factors for chronic ocular hypertension include the total number of injections, a greater frequency of injection, and preexisting glaucoma. Proposed mechanisms for chronic ocular hypertension include microparticle obstruction, toxic or inflammatory effects on trabecular meshwork, as well as alterations in outflow facility by anti-VEGF agents. Although limiting anti-VEGF therapy could minimize the risk of both acute and chronic ocular hypertension, foregoing anti-VEGF therapy risks progression of various macular diseases with resulting permanent central vision loss. While definitive evidence of damage to the retinal nerve fiber layer is lacking, patients receiving repeated injections should be monitored for ocular hypertension and patients in whom sustained ocular hypertension subsequently developed should be periodically monitored for glaucomatous changes with optic nerve optical coherence tomography and static visual fields.Item The Canonical Wnt Signaling Pathway Inhibits the Glucocorticoid Receptor Signaling Pathway in the Trabecular Meshwork(Elsevier, 2021) Sugali, Chenna Kesavulu; Rayana, Naga Pradeep; Dai, Jiannong; Peng, Michael; Harris, Sherri L.; Webber, Hannah C.; Liu, Shaohui; Dixon, Stephan G.; Parekh, Priyanka H.; Martin, Elizabeth A.; Cantor, Louis B.; Fellman, Ronald L.; Godfrey, David G.; Butler, Michelle R.; Emanuel, Matthew E.; Grover, Davinder S.; Smith, Oluwatosin U.; Clark, Abbot F.; Raghunathan, Vijay Krishna; Mao, Weiming; Ophthalmology, School of MedicineGlucocorticoid-induced glaucoma is a secondary open-angle glaucoma. About 40% of the general population may develop elevated intraocular pressure on prolonged glucocorticoid treatment secondary to damages in the trabecular meshwork (TM), a tissue that regulates intraocular pressure. Therefore, identifying the key molecules responsible for glucocorticoid-induced ocular hypertension is crucial. In this study, Dickkopf-related protein 1 (Dkk1), a canonical Wnt signaling inhibitor, was found to be elevated in the aqueous humor and TM of glaucoma patients. At the signaling level, Dkk1 enhanced glucocorticoid receptor (GR) signaling, whereas Dkk1 knockdown or Wnt signaling activators decreased GR signaling in human TM cells as indicated by luciferase assays. Similarly, activation of the GR signaling inhibited Wnt signaling. At the protein level, glucocorticoid-induced extracellular matrix was inhibited by Wnt activation using Wnt activators or Dkk1 knockdown in primary human TM cells. In contrast, inhibition of canonical Wnt signaling by β-catenin knockdown increased glucocorticoid-induced extracellular matrix proteins. At the physiological level, adenovirus-mediated Wnt3a expression decreased glucocorticoid-induced ocular hypertension in mouse eyes. In summary, Wnt and GR signaling inhibit each other in the TM, and canonical Wnt signaling activators may prevent the adverse effect of glucocorticoids in the eye.Item Cost-Comparison of Two Trabecular Micro-Bypass Stents Versus Selective Laser Trabeculoplasty or Medications Only for Intraocular Pressure Control for Patients with Open-Angle Glaucoma(Taylor & Francis, 2017) Berdahl, John P.; Khatana, Anup K.; Katz, L. Jay; Herndon, Leon; Layton, Andrew J.; Yu, Tiffany M.; Bauer, Matthew J.; Cantor, Louis B.; Ophthalmology, School of MedicineAim: Patients with open-angle glaucoma (OAG) whose intraocular pressure is not adequately controlled by one medication have several treatment options in the US. This analysis evaluated direct costs of unilateral eye treatment with two trabecular micro-bypass stents (two iStents) compared to selective laser trabeculoplasty (SLT) or medications only. Materials and methods: A population-based, annual state-transition, probabilistic, cost-of-care model was used to assess OAG-related costs over 5 years. Patients were modeled to initiate treatment in year zero with two iStents, SLT, or medications only. In years 1–5, patients could remain on initial treatment or move to another treatment option(s), or filtration surgery. Treatment strategy change probabilities were identified by a clinician panel. Direct costs were included for drugs, procedures, and complications. Results: The projected average cumulative cost at 5 years was lower in the two-stent treatment arm ($4,420) compared to the SLT arm ($4,730) or medications-only arm ($6,217). Initial year-zero costs were higher with two iStents ($2,810) than with SLT ($842) or medications only ($996). Average marginal annual costs in years 1–5 were $322 for two iStents, $777 for SLT, and $1,044 for medications only. The cumulative cost differences between two iStents vs SLT or medications only decreased over time, with breakeven by 5 or 3 years post-initiation, respectively. By year 5, cumulative savings with two iStents over SLT or medications only was $309 or $1,797, respectively. Limitations: This analysis relies on clinical expert panel opinion and would benefit from real-world evidence on use of multiple procedures and treatment switching after two-stent treatment, SLT, or polypharmaceutical initial approaches. Conclusions: Despite higher costs in year zero, annual costs thereafter were lowest in the two-stent treatment arm. Two-stent treatment may reduce OAG-related health resource use, leading to direct savings, especially over medications only or at longer time horizons.Item Primary cilia signaling mediates intraocular pressure sensation(PNAS, 2014-09-02) Luo, Na; Conwell, Michael D.; Chen, Xingjuan; Kettenhofen, Christine Insinna; Westlake, Christopher J.; Cantor, Louis B.; Wells, Clark D.; Weinreb, Robert N.; Corson, Timothy W.; Spandau, Dan F.; Joos, Karen M.; Iomini, Carlo; Obukhov, Alexander G.; Sun, Yang; Department of Medicine, IU School of MedicineLowe syndrome is a rare X-linked congenital disease that presents with congenital cataracts and glaucoma, as well as renal and cerebral dysfunction. OCRL, an inositol polyphosphate 5-phosphatase, is mutated in Lowe syndrome. We previously showed that OCRL is involved in vesicular trafficking to the primary cilium. Primary cilia are sensory organelles on the surface of eukaryotic cells that mediate mechanotransduction in the kidney, brain, and bone. However, their potential role in the trabecular meshwork (TM) in the eye, which regulates intraocular pressure, is unknown. Here, we show that TM cells, which are defective in glaucoma, have primary cilia that are critical for response to pressure changes. Primary cilia in TM cells shorten in response to fluid flow and elevated hydrostatic pressure, and promote increased transcription of TNF-α, TGF-β, and GLI1 genes. Furthermore, OCRL is found to be required for primary cilia to respond to pressure stimulation. The interaction of OCRL with transient receptor potential vanilloid 4 (TRPV4), a ciliary mechanosensory channel, suggests that OCRL may act through regulation of this channel. A novel disease-causing OCRL allele prevents TRPV4-mediated calcium signaling. In addition, TRPV4 agonist GSK 1016790A treatment reduced intraocular pressure in mice; TRPV4 knockout animals exhibited elevated intraocular pressure and shortened cilia. Thus, mechanotransduction by primary cilia in TM cells is implicated in how the eye senses pressure changes and highlights OCRL and TRPV4 as attractive therapeutic targets for the treatment of glaucoma. Implications of OCRL and TRPV4 in primary cilia function may also shed light on mechanosensation in other organ systems.Item Prostaglandin-associated periorbitopathy syndrome (PAPS): Addressing an unmet clinical need(Taylor & Francis, 2022) Sakata, Rei; Chang, Pei-Yao; Sung, Kyung Rim; Kim, Tae-Woo; Wang, Tsing-Hong; Perera, Shamira A.; Cantor, Louis B.; Ophthalmology, School of MedicineBackground: Topical prostaglandin analogs (PGAs) are widely approved and preferred first-line options for glaucoma and elevated intraocular pressure (IOP). However, prostaglandin-associated periorbitopathy syndrome (PAPS) is now a well-recognized clinical and cosmetic concern for patients receiving PGAs, especially during long-term and unilateral therapy. PGA-associated periocular changes occur in a substantial proportion of patients, with older patients (>60 years) at greater risk of clinical presentation. PAPS may hinder long-term management of glaucoma, including treatment adherence, ophthalmic surgery outcomes, and reliable IOP measurements. Recommendation: New therapeutic approaches may address this unmet clinical need. Omidenepag isopropyl (OMDI) is a novel, non-prostaglandin, selective EP2 receptor agonist in ongoing development, which provides a unique pharmacological mechanism of action. OMDI appears to provide IOP reductions comparable to PGAs, but without PAPS-related undesirable effects. OMDI may offer a suitable long-term option for patients who demonstrate decreased efficacy, or failure, of PGAs, plus patients with significant PAPS, while fulfilling international guidelines.