Ophthalmology Commons^™

Identification Of The Vibrational Optical Coherence Tomography Corneal Cellular Peak, Nathalie D. Daher, Ahmed Saeed Saad, Hiram J. Jimenez, Tatyana Milman, Orlando G. Gonzalez-Martinez, Tanmay S. Deshmukh, Jose S. Pulido, Frederick H. Silver, Dominick A. Benedetto, Christopher J. Rapuano, Zeba A. Syed

Wills Eye Hospital Papers

Purpose: Our team previously identified the presence of five corneal resonant frequency (RF) peaks in healthy volunteers using vibrational optical coherence tomography (VOCT). Prior studies have suggested that the ≤100 Hz RF peak represents the cellular element of tissue. The aim of this study was to confirm that this peak reflects the human corneal cellular component using VOCT and histological analysis.

Methods: Two human research globes were obtained from the same donor, and VOCT measurements were collected from the full-thickness corneas. A microkeratome was then used to create serial-free corneal caps from each cornea, with VOCT performed on the residual …

Incidence And Prevalence Of Keratoconus Based On Scheimpflug Imaging, Elsie Chan, Elaine W. Chong, Samantha Sze-Yee Lee, Maria Franchina, Seyhan Yazar, Peter Eastwood, Nigel Mcardle, David A. Mackey, Gareth Lingham

Articles

The prevalence of keratoconus (Belin/Ambrόsio Enhanced Ectasia Display Score ≥2.6 on Scheimpflug imaging) in a longitudinal, community cohort study from Western Australia was 3.4% (n=26/755). Keratoconus incidence over an 8-year period was 2.2% (n=15/669).

Late Descemet Membrane Detachment After Uneventful Cataract Surgery, Lovaglio Cançado Trindade, Renata Attanasio De Rezende, Tiago Bisol, Christopher J Rapuano

Wills Eye Hospital Papers

Purpose: To report 5 patients with late Descemet membrane (DM) detachment after uneventful cataract surgery.

Observations: After a retrospective chart analysis of consecutive patients that developed DM detachment after uneventful cataract surgery, six eyes of five patients were enrolled. In all cases, patients reported good vision initially after cataract surgery. Within days to months, these patients developed late DM detachment with decreased vision. In one patient, the detachment affected both eyes. Filtered air or diluted sulfur hexafluoride were injected in the anterior chamber to tamponade the DM detachment. In five eyes, the cornea cleared after DM reattachment. In two eyes …

In Vivo Determination Of The Human Corneal Elastic Modulus Using Vibrational Optical Coherence Tomography, Marcos A. Crespo, Hiram J. Jimenez, Tanmay Deshmukh, Jose S. Pulido, Ahmed Saeed Saad, Frederick H Silver, Dominick A Benedetto, Christopher J Rapuano, Zeba Syed

Wills Eye Hospital Papers

Purpose: To determine the in vivo elastic modulus of the human cornea using vibrational optical coherence tomography (VOCT).

Methods: Vibrational analysis coupled with optical coherence tomography (OCT) was used to obtain the resonant frequency (RF) and elastic modulus of corneal structural components. VOCT corneal thickness values were measured using OCT images and correlated with corneal thickness determined with Pentacam (Oculus, Wetzlar, Germany). Moduli were obtained at two locations: central cornea (CC) and inferior cornea (IC). Measurements were obtained with and without anesthetic eye drops to assess their effect on the modulus measurements.

Results: VOCT thickness values correlated positively (R2 = …

Corneal Disease And Air Pollution Levels In Detroit: Preliminary Results And Future Directions​, Sachin Ketkar, Matthew Silbergleit, Vaama Patel

Medical Student Research Symposium

Purpose: To determine if Detroit zip codes with elevated air pollution levels demonstrate increased incidence of corneal disease.

Background: 82 million people in the United States live in counties with air quality concentrations above the National Ambient Air Quality Standards. Air pollution’s detrimental effects on an individual’s health has been well documented. Much of this research has focused on the pulmonary system. The eye, another mucous membrane exposed to the external environment, has been largely ignored

Methods: After an initial literature review of similar studies, 14 corneal diseases and 5 pollutants were selected to be evaluated. Kresge Eye Institute’s patient …

A Systematic Review On Three Major Types Of Scleral-Fixated Intraocular Lens Implantation, Ho Ming Wong, Ka Wai Kam, Christopher J Rapuano, Alvin L Young

Wills Eye Hospital Papers

PURPOSE: We performed a systematic review on 3 major types of scleral-fixated intraocular lens (SFIOL) implantations and conducted subgroup analyses on pediatric population and subjects with Marfan syndrome.

DESIGN: Systematic review.

METHODS: We performed a search in PubMed, Ovid MEDLINE, and Embase for English language articles with keywords "(sutured intraocular lens) OR (SFIOL) OR (sutureless intraocular lens) OR (glued intraocular lens) OR (intrascleral intraocular lens) OR (SFIOL)" through October 16, 2019. Articles reporting individual outcomes after SFIOL were included in this systematic review. Recorded outcome measures included intraoperative and postoperative complications, endothelial cell changes, and intraocular lens-related outcomes.

RESULTS: Our …

Pterygium Recurrence And Corneal Stabilization Point After Pterygium Excision Using The Controlled Partial Avulsion Fibrin Glue Technique, Mohd Radzi Hilmi, Khairidzan Mohd Kamal, Mohd Zulfaezal Che Azemin

Makara Journal of Health Research

Background: This study aimed to evaluate the pterygium recurrence rate and corneal stabilization point after pterygium excision via the controlled partial avulsion fibrin glue technique using multiple corneal parameters.

Methods: One hundred eyes of 100 patients who had undergone primary pterygium excision surgery via the controlled partial avulsion fibrin glue technique were retrospectively reviewed. Corneal stabilization points were determined over four follow-up sessions (i.e., the 1st, 3rd, 6th, and 12th months after surgery) based on changes in Simulated-K, corneal irregularity measurement, shape factor, and toric mean keratometry. Post-operative courses were followed for 12 months after surgery. Recurrence was …

A Foldable Nonpenetrating Keratoprosthesis: Medium To Long-Term Clinical Results In Patients With Corneal Blindness Due To Noninflammatory Anterior Cornea Disease., Jose M Vargas, Eric Shiuey

Department of Medicine Faculty Papers

PURPOSE: To report the medium to long-term safety and performance outcomes of the KeraKlear nonpenetrating artificial cornea (KeraKlear) as the primary procedure in patients with corneal blindness due to noninflammatory anterior cornea disease.

METHODS: Fifteen patients with corneal blindness (preoperative visual acuity [VA] of ≥20/200) due to a non-inflammatory anterior corneal condition were included in this prospective, single-center study. Preoperative diagnoses included corneal scars, keratoconus, and corneal dystrophies. Diseased corneas were implanted with the KeraKlear (KeraMed Inc., Irvine, California, USA) by a single surgeon (JMV) using a femtosecond laser to create all incisions. Participants were followed up with for as …

Tumors Of The Conjunctiva And Cornea., Carol L. Shields, Jerry A. Shields

Wills Eye Hospital Papers

Tumors of the conjunctiva and cornea comprise a large and varied spectrum of conditions. These tumors are grouped into two major categories of congenital and acquired lesions. The acquired lesions are further subdivided based on origin of the mass into surface epithelial, melanocytic, vascular, fibrous, neural, histiocytic, myxoid, myogenic, lipomatous, lymphoid, leukemic, metastatic and secondary tumors. Melanocytic lesions include nevus, racial melanosis, primary acquired melanosis, melanoma, and other ocular surface conditions like ocular melanocytosis and secondary pigmentary deposition. The most frequent nonmelanocytic neoplastic lesions include squamous cell carcinoma and lymphoma, both of which have typical features appreciated on clinical examination. …

Molecular Mechanisms Of Suberoylanilide Hydroxamic Acid In The Inhibition Of Tgf-Β1-Mediated Canine Corneal Fibrosis, Kristina M. Gronkiewicz, Elizabeth A. Giuliano, Ajay Sharma, Rajiv R. Mohan

Pharmacy Faculty Articles and Research

Objective—To investigate molecular mechanisms mediating anti-fibrotic effect of SAHA in the canine cornea using an in vitro model. We hypothesized that SAHA attenuates corneal fibrosis by modulating Smad-dependent and, to a lesser extent, Smad-independent signaling pathways activated by TGF-β1, as well as matrix metalloproteinase (MMP) activity.

Methods—Cultured canine corneal fibroblasts (CCF) were incubated in the presence/absence of TGF-β1 (5ng/ml) and SAHA (2.5μM) for 24hrs. Western blot analysis was used to quantify non-phosphorylated and phosphorylated isoforms of Smad2/3, p38 MAP kinase (MAPK), ERK1/2 and JNK1. Real-time PCR and zymography were utilized to quantify MMP1, MMP2, MMP8 and MMP9 mRNA expression and …

Characterization Of Inhibitor Of Differentiation (Id) Proteins In Human Cornea, Rajiv R. Mohan, Brandie R. Morgan, Govinduraj Anumanthan, Ajay Sharma, Shyam S. Chaurasia, Frank G. Rieger

Pharmacy Faculty Articles and Research

Inhibitor of differentiation (Id) proteins are DNA-binding transcription factors involved in cellular proliferation, migration, inflammation, angiogenesis and fibrosis. However, their expression and role in the cornea is unknown. The present study was undertaken to characterize the expression of Id proteins and their interactions with the pro-fibrotic cytokine Transforming Growth Factor β1 (TGFβ1) and anti-fibrotic cytokine, bone morphogenic protein 7 (BMP7) in human cornea. Human donor corneas procured from Eye Bank were used. Id proteins were localized in human corneal sections using immunofluorescence. Primary cultures of human corneal fibroblasts (HCF) were established and treated with either TGFβ1 (5 ng/ml) or BMP7 …

The Influence Of Soft Contact Lens Wear And Two Weeks Cessation Of Lens Wear On Corneal Curvature, Aoife Lloyd Mckernan, Veronica O'Dwyer, Luisa Simo Mannion

Articles

Abstract

Introduction

Accurate corneal measurements are crucial in corneal refractive surgery (CRS) to ensure successful outcomes. Soft contact lens (SCL) wear may result in changes to corneal curvature and structure. United States Food and Drug Administration (FDA) pre-operative guidelines recommend that prior to CRS, SCL wearers cease SCL wear for “at least two weeks before examination and treatment”[1]. Corneal curvature changes induced by SCL wear may take longer than two weeks to resolve.

Purpose

To examine the effect of SCL wear on corneal curvature before and following two weeks SCL wear cessation. To explore the possible impact of different SCL …

Corneal Gene Therapy: Basic Science And Translational Perspective, Rajiv R. Mohan, Jason T. Rodier, Ajay Sharma

Pharmacy Faculty Articles and Research

Corneal blindness is the third leading cause of blindness worldwide. Gene therapy is an emerging technology for corneal blindness due to the accessibility and immune-privileged nature of the cornea, ease of vector administration and visual monitoring, and ability to perform frequent noninvasive corneal assessment. Vision restoration by gene therapy is contingent upon vector and mode of therapeutic gene introduction into targeted cells/tissues. Numerous efficacious vectors, delivery techniques, and approaches have evolved in last decade for developing gene-based interventions for corneal diseases. Maximizing the potential benefits of gene therapy requires efficient and sustained therapeutic gene expression in target cells, low toxicity, …

Corneal Replication Is An Interferon Response-Independent Bottleneck For Virulence Of Herpes Simplex Virus 1 In The Absence Of Virion Host Shutoff, Tracy J. Pasieka, Vineet D. Menachery, Pamela C. Rosato, David A. Leib

Dartmouth Scholarship

Herpes simplex viruses lacking the virion host shutoff function (Δvhs) are avirulent and hypersensitive to type I and type II interferon (IFN). In this study, we demonstrate that even in the absence of IFN responses in AG129 (IFN-αβγR^−/−) mice, Δvhs remains highly attenuated via corneal infection but is fully virulent via intracranial infection. The data demonstrate that the interferon-independent inherent replication defect of Δvhs has a significant impact upon peripheral replication and neuroinvasion.

Substance P And The Host Immune Response, Megan Elizabeth Foldenauer

Wayne State University Dissertations

This body of work examined the mechanism by which SP regulates host immunity, specifically, its control of growth factors and TLR expression in the P. aeruginosa-infected cornea. The role of mTOR and VIP in corneal infection and inflammation also was tested.

SP has a dual role in bacterial infection, unexpectedly upregulating growth factor production. This was accompanied by macrophage-specific upregulation of pro-inflammatory cytokines, downregulation of anti-inflammatory cytokines, and upregulation of anti-apoptotic genes, as well as a decrease in arginase-producing macrophages (M2 cells), important in stromal healing in these mice. All of these lead to worsened disease, despite the stimulatory effects …

Gene Therapy In The Cornea: 2005--Present, Rajiv R. Mohan, Jonathan C. K. Tovey, Ajay Sharma, Ashish Tandon

Pharmacy Faculty Articles and Research

Successful restoration of vision in human patients with gene therapy affirmed its promise to cure ocular diseases and disorders. The efficacy of gene therapy is contingent upon vector and mode of therapeutic DNA introduction into targeted cells/tissues. The cornea is an ideal tissue for gene therapy due to its ease of access and relative immune-privilege. Considerable progress has been made in the field of corneal gene therapy in last 5 years. Several new gene transfer vectors, techniques and approaches have evolved. Although corneal gene therapy is still in its early stages of development, the potential of gene-based interventions to treat …

Polyethylenimine-Conjugated Gold Nanoparticles: Gene Transfer Potential And Low Toxicity In The Cornea, Ajay Sharma, Ashish Tandon, Jonathan C. K. Tovey, Rangan Gupta, J. David Robertson, Jennifer A. Fortune, Alexander M. Klibanov, John W. Cowden, Frank G. Rieger, Rajiv R. Mohan

Pharmacy Faculty Articles and Research

This study examined the gene transfer efficiency and toxicity of 2-kDa polyethylenimine conjugated to gold nanoparticles (PEI2-GNP) in the human cornea in vitro and rabbit cornea in vivo. PEI2-GNP with nitrogen-to-phosphorus (N/P) ratios of up to 180 exhibited significant transgene delivery in the human cornea without altering the viability or phenotype of these cells. Similarly, PEI2-GNP applied to corneal tissues collected after 12 h, 72 h, or 7 days exhibited appreciable gold uptake throughout the rabbit stroma with gradual clearance of GNP over time. Transmission electron microscopy detected GNP in the keratocytes and the extracellular matrix of the rabbit corneas. …

Defensins In Ocular Immunity, Minhao Wu

Wayne State University Dissertations

Corneal infection with P. aeruginosa results in corneal perforation in susceptible

B6, but not resistant BALB/c mice. This study explored their role mBD 1-4 in corneal

infection, and their potential synergy. Immunostaining and real-time RT-PCR data

demonstrated that their expression was either constitutive (mBD1 and mBD2) or

inducible (mBD3 and mBD4) in normal BALB/c and B6 corneas, and disparately

regulated in BALB/c vs B6 corneas after infection. Knock down studies using siRNA

treatment indicated that mBD2 and mBD3, but neither mBD1 nor mBD4, is required in

ocular defense. Moreover, in vivo studies demonstrated individual and combined effects

of mBD2 and …

"Transduction Efficiency Of Aav 2/6, 2/8 And 2/9 Vectors For Delivering Genes In Human Corneal Fibroblasts ", Ajay Sharma, Arkasubhra Ghosh, Eric T. Hansen, Jason M. Newman, Rajiv R. Mohan

Pharmacy Faculty Articles and Research

In the present study, cellular tropism and relative transduction efficiency of AAV2/6, AAV2/8 and AAV2/9 vectors have been tested for the cornea using primary cultures of human corneal fibroblasts. The AAV6, AAV8 and AAV9 serotypes having AAV2 ITR plasmid encoding for alkaline phosphatase (AP) gene were generated by transfecting HEK293 cell line with pHelper, pARAP4 and pRep/Cap plasmids. Primary cultures of human corneal fibroblasts were exposed to AAV infectious particles at two different doses (1×105 and 2×105 MOI). Cytochemistry and enzyme assays were used to measure delivered transgene expression in samples collected at 4 and 30 hours after AAV infection …

Role Of Transforming Growth Factor Beta In Corneal Function, Biology And Pathology, Ashish Tandon, Jonathan C. K. Tovey, Ajay Sharma, Rangan Gupta, Rajiv R. Mohan

Pharmacy Faculty Articles and Research

Transforming growth factor-beta (TGFβ) is a pleiotropic multifunctional cytokine that regulates several essential cellular processes in many parts of the body including the cornea. Three isoforms of TGFβ are known in mammals and the human cornea expresses all of them. TGFβ1 has been shown to play a central role in scar formation in adult corneas whereas TGFβ2 and TGFβ3 have been implicated to play a critical role in corneal development and scarless wound healing during embryogenesis. The biological effects of TGFβ in the cornea have been shown to follow SMAD dependent as well as SMAD-independent signaling pathways depending upon cellular …

Aav Serotype Influences Gene Transfer In Corneal Stroma In Vivo, Ajay Sharma, Jonathan C. K. Tovey, Arkasubhra Ghosh, Rajiv R. Mohan

Pharmacy Faculty Articles and Research

This study evaluated the cellular tropism and relative transduction efficiency of three AAV serotypes, AAV6, AAV8 and AAV9, for corneal gene delivery using mouse cornea in vivo and donor human cornea ex vivo. The AAV6, AAV8 and AAV9 serotypes having AAV2 plasmid encoding for alkaline phosphatase (AP) gene were generated by transfecting HEK293 cell line with pHelper, pARAP4 and pRep/Cap plasmids. Viral vectors (109 vg/μl) were topically applied onto mouse cornea in vivo and human cornea ex vivo after removing the epithelium. Human corneas were processed for transgene delivery at day 5 after viral vector application. Mouse corneas were harvested …

Isolation And Cultivation Of Equine Corneal Keratocytes, Fibroblasts And Myofibroblasts, Dylan G. Buss, Elizabeth A. Giuliano, Ajay Sharma, Rajiv R. Mohan

Pharmacy Faculty Articles and Research

Objective—To establish an in vitro model for the investigation of equine corneal wound healing. To accomplish this goal, a protocol to isolate and culture equine corneal keratocytes, fibroblasts and myofibroblasts was developed.

Animal material—Equine corneal buttons were aseptically harvested from healthy research horses undergoing humane euthanasia for reasons unrelated to this study. Slit-lamp biomicroscopy was performed prior to euthanasia by a board-certified veterinary ophthalmologist to ensure that all samples were harvested from horses free of anterior segment disease.

Procedure—Equine corneal stroma was isolated using mechanical techniques and stromal subsections were then cultured. Customized media at different culture conditions was used …

Efficacy And Safety Of Mitomycin C As An Agent To Treat Corneal Scarring In Horses Using An In Vitro Model, Dylan G. Buss, Ajay Sharma, Elizabeth A. Giuliano, Rajiv R. Mohan

Pharmacy Faculty Articles and Research

Objective—Mitomycin C (MMC) is used clinically to treat corneal scarring in human patients. We investigated the safety and efficacy of MMC to treat corneal scarring in horses by examining its effects at the early and late stages of disease using an in-vitro model.

Procedure—An in-vitro model of equine corneal fibroblast (ECF) developed was used. The equine corneal fibroblast or myofibroblast cultures were produced by growing primary ECF in the presence or absence of transforming growth factor beta-1 (TGFβ1) under serum-free conditions. The MMC dose for the equine cornea was defined with dose-dependent trypan blue exclusion and MTT [(3-4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] assays …

Stromal Haze, Myofibroblasts, And Surface Irregularity After Prk, Marcelo V. Netto, Rajiv R. Mohan, Sunilima Sinha, Ajay Sharma, William Dupps, Steven E. Wilson

Pharmacy Faculty Articles and Research

The aim of this study was to investigate the relationship between the level of stromal surface irregularity after photorefractive keratectomy (PRK) and myofibroblast generation along with the development of corneal haze.

Variable levels of stromal surface irregularity were generated in rabbit corneas by positioning a fine mesh screen in the path of excimer laser during ablation for a variable percentage of the terminal pulses of the treatment for myopia that does not otherwise generate significant opacity. Ninety-six rabbits were divided into eight groups[.]

Slit lamp analysis and haze grading were performed in all groups. Rabbits were sacrificed at 4 hr …