Publications by authors named "Mark A Greiner"

Purpose: To study clinical characteristics and outcomes of penetrating keratoplasty (PK) and deep anterior lamellar keratoplasty (DALK) wound dehiscence.

Methods: This retrospective case series assessed PK and DALK recipients with wound dehiscence at a single institution. We evaluated relationships between dehiscence etiologies, transplant indications, ocular/systemic comorbidities, keratoplasty type, and adverse post-dehiscence outcomes, especially graft failure and visual loss.

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Purpose: To identify areas of consensus among global experts for the management of Fuchs endothelial corneal dystrophy (FECD) in clinical practice, including its diagnosis, evaluation, decision-making principles with respect to intervention, and recommendations for performing cataract surgery in patients with FECD, including when to combine with keratoplasty.

Design: Modified Delphi-based global consensus.

Participants: Thirty-seven ophthalmologists from around the world with significant expertise in the management and mechanisms of FECD.

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Purpose: The aim of this study was to quantify nighttime driving differences in patients with Fuchs endothelial corneal dystrophy (FECD) using the FDA-validated National Advanced Driving Simulator MiniSim.

Methods: We conducted a pilot study to calculate sample size, followed by a prospective study with 6 patients with FECD and 6 controls. Participants underwent Snellen visual acuity (VA) testing, Mars contrast sensitivity (CS) assessment, and Scheimpflug tomography.

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Purpose: Evidence suggests that corneal endothelial cell (CEC) death in Fuchs endothelial corneal dystrophy (FECD) is due to ferroptosis, an iron-mediated cell death. Iron-sulfur cluster (ISC)-containing aconitases and the iron responsive element binding proteins IREBP1 and IREBP2 are known mediators of iron homeostasis. This study investigates mechanisms underlying iron dysregulation in CECs and proposes a role for ISCs and IREBPs in the context of FECD pathogenesis.

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Purpose: Describe aims, methods, characteristics of donors, donor corneas and recipients, and potential impact of the Diabetes Endothelial Keratoplasty Study (DEKS).

Methods: The DEKS is a randomized, clinical trial to assess graft success and endothelial cell density (ECD) 1 year after Descemet membrane endothelial keratoplasty (DMEK) using corneas from donors with versus without diabetes in a 1:2 minimization assignment. Diabetes severity in the donor is assessed by medical history, postmortem HbA1c, and donor skin advanced glycation end-products and oxidation markers.

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Objective: To evaluate the published literature on the efficacy of amniotic membrane grafting (AMG) in the management of acute chemical and thermal ocular surface burns with respect to the rate of corneal re-epithelialization and improvement of visual acuity or corneal clarity.

Methods: Literature searches were conducted in the PubMed database in May 2023 and updated in January 2024 and were limited to the English language without date restrictions. The searches yielded 474 citations; 58 were reviewed in full text, and 9 met the inclusion criteria.

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Fuchs endothelial corneal dystrophy (FECD), the leading indication for corneal transplantation in the U.S., causes loss of corneal endothelial cells (CECs) and corneal edema leading to vision loss.

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Article Synopsis
  • The text reviews the safety and effectiveness of epithelium-off corneal collagen cross-linking (CXL) as a treatment for progressive corneal ectasia, specifically keratoconus (KCN) and ectasia after refractive surgery.
  • A comprehensive literature search led to the inclusion of 6 high-quality randomized clinical trials, all showing positive outcomes, including decreased progression rates and improved visual acuity in patients undergoing treatment compared to controls.
  • The findings indicate that epithelium-off CXL is effective in managing KCN and post-refractive surgery ectasia with a low incidence of complications, suggesting a favorable safety profile.
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Purpose: To review the published literature on the safety and outcomes of keratolimbal allograft (KLAL) transplantation and living-related conjunctival limbal allograft (lr-CLAL) transplantation for bilateral severe/total limbal stem cell deficiency (LSCD).

Methods: Literature searches were last conducted in the PubMed database in February 2023 and were limited to the English language. They yielded 523 citations; 76 were reviewed in full text, and 21 met the inclusion criteria.

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Changes in the anterior segment of the eye due to type 2 diabetes mellitus (T2DM) are not well-characterized, in part due to the lack of a reliable animal model. This study evaluated changes in the anterior segment, including crystalline lens health, corneal endothelial cell density, aqueous humor metabolites, and ciliary body vasculature, in a rat model of T2DM compared with human eyes. Male Sprague-Dawley rats were fed a high-fat diet (45% fat) or normal diet, and rats fed the high-fat diet were injected with streptozotocin intraperitoneally to generate a model of T2DM.

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Article Synopsis
  • The cornea interacts with mechanical forces to maintain its structure, transparency, and refractive power, with cells responding to these forces impacting their development and health.
  • Recent advances in corneal mechanobiology highlight the roles of mechanical forces on different corneal cell types and underscore species-specific differences useful for animal model studies.
  • Identifying knowledge gaps and opportunities for therapeutic interventions in conditions like keratoconus and Fuchs' dystrophy can improve our understanding and treatment of corneal diseases.
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Purpose: To review the published literature on the diagnostic capabilities of the newest generation of corneal imaging devices for the identification of keratoconus.

Methods: Corneal imaging devices studied included tomographic platforms (Scheimpflug photography, OCT) and functional biomechanical devices (imaging an air impulse on the cornea). A literature search in the PubMed database for English language studies was last conducted in February 2023.

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Purpose: The aim of this study was to define risks for corneal transplantation associated with fibrous ingrowth among first-time transplant recipients.

Methods: We performed a retrospective case-control study of patients with a histopathologic diagnosis of fibrous ingrowth between 2002 and 2019. Patients with fibrous ingrowth from a first corneal specimen were included.

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Purpose: There is a pressing need to investigate the impact of type II diabetes mellitus on the posterior cornea in donor tissues given its increasing prevalence and potential impact on endothelial keratoplasty surgical outcomes.

Methods: Immortalized human cultured corneal endothelial cells (CECs; HCEC-B4G12) were grown in hyperglycemic media for 2 weeks. Extracellular matrix (ECM) adhesive glycoprotein expression and advanced glycation end products (AGEs) in cultured cells and corneoscleral donor tissues, as well as the elastic modulus for the Descemet membrane (DMs) and CECs of diabetic and nondiabetic donor corneas, were measured.

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Purpose: We sought to define the role of Wwtr1 in murine ocular structure and function and determine the role of mechanotransduction in Fuchs' endothelial corneal dystrophy (FECD), with emphasis on interactions between corneal endothelial cells (CEnCs) and Descemet's membrane (DM).

Methods: A Wwtr1 deficient mouse colony was established, and advanced ocular imaging, atomic force microscope (AFM), and histology/immunofluorescence were performed. Corneal endothelial wound healing was assessed using cryoinjury and phototherapeutic keratectomy in Wwtr1 deficient mice.

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Mucous membrane pemphigoid is an autoimmune disease with variable clinical presentation and multiple autoantigens. To determine whether disease endotypes could be identified on the basis of the pattern of serum reactivity, the clinical and diagnostic information of 70 patients with mucous membrane pemphigoid was collected, and reactivity to dermal or epidermal antigens, using indirect immunofluorescence, and specific reactivity to bullous pemphigoid (BP) autoantigens BP180 and BP230, collagen VII, and laminin 332 were evaluated. Most patients had lesions at multiple mucosae, with the most prevalent being oropharyngeal (mouth, gingiva, pharynx; 98.

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Diabetes mellitus is a multiorgan systemic disease impacting numerous ocular structures that results in significant ocular morbidity and often results in more frequent corneal and glaucoma surgeries for affected individuals. We hypothesize that the systemic metabolic and proteomic derangement observed in the progression of diabetes influences the composition of the aqueous humor (AH), which ultimately impacts the anterior segment health of the eye. To identify changes associated with diabetes progression, we mapped the metabolite profile and proteome of AH samples from patients with varying severities of type II diabetes (T2DM).

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Purpose: To evaluate the risk factors, medical and surgical management, and visual outcomes of patients affected by keratitis (AK) over a 16-year period.

Observations: Records were reviewed retrospectively for all AK patients treated at University of Iowa between 2002 and 2017. Main outcomes measured were risk factors, time to diagnosis, coinfection types, initial and final visual acuities, and treatment outcomes, with failure of medical therapy defined as need for therapeutic keratoplasty (TK).

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Defective cellular metabolism, impaired mitochondrial function, and increased cell death are major problems that adversely affect donor tissues during hypothermic preservation prior to transplantation. These problems are thought to arise from accumulated reactive oxygen species (ROS) inside cells. Oxidative stress acting on the cells of organs and tissues preserved in hypothermic conditions before surgery, as is the case for cornea transplantation, is thought to be a major reason behind cell death prior to surgery and decreased graft survival after transplantation.

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The extracellular matrix (ECM) plays a crucial role in all parts of the eye, from maintaining clarity and hydration of the cornea and vitreous to regulating angiogenesis, intraocular pressure maintenance, and vascular signaling. This review focuses on the interactions of the ECM for homeostasis of normal physiologic functions of the cornea, vitreous, retina, retinal pigment epithelium, Bruch's membrane, and choroid as well as trabecular meshwork, optic nerve, conjunctiva and tenon's layer as it relates to glaucoma. A variety of pathways and key factors related to ECM in the eye are discussed, including but not limited to those related to transforming growth factor-β, vascular endothelial growth factor, basic-fibroblastic growth factor, connective tissue growth factor, matrix metalloproteinases (including MMP-2 and MMP-9, and MMP-14), collagen IV, fibronectin, elastin, canonical signaling, integrins, and endothelial morphogenesis consistent of cellular activation-tubulogenesis and cellular differentiation-stabilization.

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Mitochondrial function is essential for the viability of aerobic eukaryotic cells, as mitochondria provide energy through the generation of adenosine triphosphate (ATP), regulate cellular metabolism, provide redox balancing, participate in immune signaling, and can initiate apoptosis. Mitochondria are dynamic organelles that participate in a cyclical and ongoing process of regeneration and autophagy (clearance), termed mitophagy specifically for mitochondrial (macro)autophagy. An imbalance in mitochondrial function toward mitochondrial dysfunction can be catastrophic for cells and has been characterized in several common ophthalmic diseases.

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Purpose: Rho-associated kinase (ROCK) inhibitors have been successfully used as a rescue strategy in eyes that failed to clear after descemetorhexis without endothelial graft for treatment of Fuchs endothelial corneal dystrophy (FECD). The functional mechanisms by which ROCK inhibitors modulate corneal endothelial cell regeneration in FECD patients have, however, not been clarified. Here, we analyzed the effect of the ROCK inhibitor ripasudil on corneal endothelial cells of FECD patients and normal donors using ex vivo tissue and in vitro cellular models.

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Purpose: To report indications for wear, visual outcomes, and complications of EyePrintPRO (EPP) scleral contact lens (SCL) use.

Methods: A retrospective review identified all patients fitted with this device between December 2013 and March 2018. Baseline demographics, wear indication, and contact lens history were determined.

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Purpose: To assess how trypan blue staining affects Descemet membrane endothelial keratoplasty (DMEK) graft visibility and corneal endothelial cell (CEC) mitochondrial respiration.

Methods: DMEK grafts (n = 20) were stained with trypan blue 0.06% for 1, 3, 5, or 10 minutes.

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