Nandita Anand, MD
Neurodevelopment Outcomes in Patients with Stage 3 Retinopathy of Prematurity
Retinopathy of prematurity (ROP) is a leading cause of blindness among children. Treatment for this condition has changed over the years from cryotherapy to retinal laser treatment – the current standard of care. A newer treatment that holds promise is bevacizumab, initially a chemotherapy treatment for metastatic colon cancer, which was incidentally found to improve vision in adults with age related macular degeneration. Although not currently FDA approved in adults or children, large clinical trials have demonstrated that intravitreal bevacizumab may be very effective in the treatment of ROP. However, the long-term effects in premature infants, specifically the effects on the developing brain, remains unknown. The purpose of this research study is to compare the effects of neurodevelopment outcomes in babies with severe ROP who have been treated with intravitreal bevacizumab to those who have been treated with traditional laser.
Evaluation of the effects of a high-fat diet on the optic nerve head in an in vitro model for obesity and glaucoma
Glaucoma is a leading cause of blindness worldwide and affects almost 3 million Americans. Despite the significant progress made by researchers, current glaucoma medications can only partially prevent the worsening of the disease, and the slow progressive loss of vision associated with the disease still results in the permanent loss of vision in many affected individuals. In this study, we will address the question whether obesity and a diet rich in unsaturated fats can have deleterious effects on the susceptibility to or the progression of glaucoma. It is well known that obesity increases the risk for cardiovascular disease and several other eye diseases, but the effects on glaucoma have not been studied systematically to date. In order to answer this question, we have developed a cellular model system in which we can test the effects of a high-fat diet on the specific cell type affected in glaucoma. Results from the proposed research will provide important information on risk factors for glaucoma patients and may help improve disease management.
Direct application of Matrix-Assisted Laser Desorption/Ionization-Time of Flight Mass Spectrometry (MALDI-TOF MS) on aqueous and vitreous samples for rapid endophthalmitis diagnosis.
Endophthalmitis is a severe intraocular infection frequently resulting in blindness within days. Early recognition of the microorganism and initiation of appropriate treatment are crucial for halting rapid progression to blindness, especially when empiric treatments fail. Currently, diagnosis with cultures frequently fails to identify the cause and takes days. MALDI-TOF mass spectrometry (MS) is a novel technology that has dramatically changed microbiology by offering faster diagnosis and identifying more microorganisms at significantly reduced costs. The purpose of this pilot study is to investigate the application of MALDI-TOF MS for the rapid diagnosis of endophthalmitis. Our proposal could validate MALDI-TOF MS as a new technique, thus revolutionizing current endophthalmitis protocols, leading to faster initiation of appropriate treatment, and paving the way to enable future specialized treatments against toxins of each microorganism.
Investigating Association of Intravitreous anti-VEGF Therapy and Renal Function
Vascular endothelial growth factor (VEGF) is a protein important for blood vessels in the kidneys and eyes. Some diseases like diabetes and age-related macular degeneration cause eye disease because of too much VEGF in the eyes. To prevent vision loss in these diseases, ophthalmologists often give an injection in the eye that delivers medicine to lower the amount of VEGF. Sometimes this medicine can be absorbed into the body and travel to the kidneys. This can damage the kidneys and would be a serious side-effect especially in patients who have weakened kidneys. This is a unique study designed to look at a large number of patients at Northwestern to see if indeed there is a pattern of reduced kidney function associated with repeated eye injections of anti-VEGF medicine.
Rebecca Deutsch, MD
Developing a Grading System for Vitreous Floaters Using Motion Analysis Software in the Symptomatic PVD Patient
Floaters occur when the vitreous jelly liquefies over time, becoming mobile in the large cavity in the back of the eye. These clumps of vitreous can often be detected by patients, and can be quite bothersome. Conventionally, intervention is not taken and floaters typically become less noticeable to patients as the settle away from the center of vision. However, recently ophthalmologists have been performing laser ablation or surgical vitreous removal for patients that are particularly symptomatic. This study aims to more objectively characterize the symptoms these patients are experiencing using and validating a novel grading system . We will use motion analysis technology in conjunction with the tools we have in clinic to visualize floaters (OCT, B scan). Floaters will also be assessed using more conventional measures like a quality of life survey, Snellen visual acuity, contrast sensitivity testing, and wavefront abberometry. After undergoing either laser or surgical intervention, patients will be reassessed with the same metrics to assess symptom improvement.
The Therapeutic Effect of Novel Anti-Inflammatory Peptide ZEP in an Experimental Dry Eye Model
Dry Eye Disease (DED) is a disorder that affects millions of people worldwide and in severe circumstances can lead to blindness. Although the means behind how DED works is not fully understood, inflammation of the eyes is a well-known hallmark of DED. This inflammation is mediated both by activation of intracellular structures and signaling pathways. Recently, it has been shown that many anti-viral drugs also possess anti-inflammatory properties. Our preliminary data suggests that a novel anti-viral drug derived from snake venom named ZEP improves corneal cell viability 8-fold as well as acts as an anti-inflammatory in mouse macrophages. The goal of this study is to determine whether ZEP decreases inflammation in corneal epithelial cells in an attempt to decrease severity of Dry Eye Disease.
Understanding the role of Heparanase in Herpetic Keratitis
Ocular infections are a common cause for the vision loss. Herpes simplex virus type-1 (HSV-1) causes hrptic keratitis which is one of the main causes of infectious blindness in the USA. Currently prescribed drugs such as nucleoside analogs, acyclovir and its derivatives, ganciclovir and foscarnet, can cause severe side effects including renal failure, fetal abnormalities, and fail to prevent emergence of drug-resistant viral strains. In this proposal, our goal is to uncover novel pathways involved in the HSV-1 entry, replication and egress which can lay foundation to new drugs that target these pathways to curb infection. We have previously shown in cell culture models, the importance of Heparanase (HPSE; a host enzyme) in HSV-1 infections, specifically its necessity in viral egress. Our preliminary studies have shown that there could be a strong correlation between HSV-1 entry, activation of Nuclear Factor kB (NF-kB) and upregulation of HPSE which in-turn cause viral egress and tissue scarring. In this proposal we go one step further in understanding the role of HPSE and other host factors responsible for viral spread, egress and disease progression.
Utilizing OCTA to Characterize and Compare the Choriocapillaris in African Americans and Caucasians
Age-related macular degeneration (AMD) is a leading cause of blindness in the United States. It is estimated that 7.2 million US citizens have AMD, and almost 1 million of them suffer from the advanced form. Interestingly, elderly African Americans are much less likely to develop AMD than Caucasians. It is suspected that decreased blood flow to the outer retina and RPE, coming from the choriocapillaris, may play a vital role in the AMD process. It would be beneficial, then, to use a new imaging technique called optical coherence tomography angiography (OCTA) to investigate and compare the choriocapillaris characteristics in healthy African and Caucasian Americans. This study may provide insight into the factors involved in lower risk of AMD in African Americans and help us better understand the mechanisms of AMD development.
Characterizing the nature of retina-infiltrating T cells in a mouse model of autoimmune uveitis
Uveitis accounts for 10-15% of people afflicted with legal blindness in the developed world. It results from immune-mediated destruction of the light-sensitive photoreceptor cells of the neuroretina, but the pathogenic trigger is unknown in most cases. The proposed study will address fundamental questions regarding the nature of retina-infiltrating T cells and will reveal the predominant immune mechanisms that regulate these cells. This research is relevant to public health because an understanding of the mechanisms regulating retinainfiltrating T cells will inform strategies aimed at manipulating these processes for clinical benefit in the context of uveitis.
Madeline Ripa, MD
Composition, Indication, and Outcomes of Autologous Serum Tears in Chicago
The components of the tear film are important to maintain the normal health of the eye and the ocular surface. There are many different causes of dry eye causing symptoms of dryness, irritation, light sensitivity, foreign body sensation, red eyes and poor vision. The use of artificial tears as a first line substitute of the normal tears. This treatment, however, is sometimes inadequate because it lacks the biological nutrients found in the natural tear film. Eye drops made from a portion of a patient’s blood are known as autologous serum tears. These have been studied for use in certain conditions because they have many of the same nutrients as natural tears. The purpose of this research is to study 1) the composition of serum tears from different vendors, 2) the different reasons for prescribing serum tears, and 3) the level of benefit from the serum tears for the different indications.
Conjunctival microvascular hemorheologic metrics in type II diabetes mellitus
Development of diabetic complications often occurs without warning. Problems such as diabetic retinopathy, which can lead to permanent vision loss may develop suddenly particularly among individuals with poor sugar control. Previous studies have suggested that reduced or irregular blood flow in small blood vessels may precede diabetic complications. Development of tools that help one identify these abnormalities would be helpful as a marker of diabetic complications. The purpose of this study, therefore, is to test a method of identifying sluggish blood flow in the small blood vessels of the white of the eye that may precede complications such as diabetic retinopathy related to elevation in blood sugar.
The role of IL-13 and granulysin in the pathogenesis of Stevens-Johnson Syndrome/Toxic Epidermal Necrolysis
Steven Johnson Syndrome (SJS) and Toxic Epidermal Necrolysis (TEN) are very rare diseases but they have a high mortality rate. In the severe cases, they are followed by a lot of complications involving different organs which lead at the end to a multi organ failure then death. One of the major complications is that it leads to visual impairment and blindness. The pathogenies of the disease is not fully understood yet. The patients with SJS/TEN are usually seen by different physicians involving multidisciplinary approach in the management of this disease. There is yet no definitive specific treatment for this condition especially since the pathophysiology is not completely understood. Granulysin is reported to be a key mediator for disseminated keratinocyte death in Stevens Johnson syndrome and toxic epidermal necrolysis. However, its role in the precise mechanism of ocular surface disease is not fully understood. The association of combined IL-13/IL-4R signaling pathway gene polymorphism with SJS accompanied by ocular surface complications has been reported. Although, the expression of cytokines and chemokine receptors in the cutaneous lesions of SJS has been reported earlier, their precise roles in development of ocular surface disease has not been completely studied. This study will be focused on the expression of granulysin and IL-13 in the skin and blood of patients with SJS/TEN as studied by immunohistochemistry and ELISA techniques. The levels of IL-13 and granulysin will be correlated with the degree of ocular surface disease in these patients by referring to the patient charts.
Autophagy and Retinal Post-Ischemic Conditioning
Central retinal artery occlusion (CRAO) due to thrombus or embolism develops into retinal ischemia, often with visual acuity less than 20/400, at an incidence of 1-15/10,000 yearly. Severe visual loss increases health care costs, mortality and depression; and decreases productivity, independence, and quality of life. CRAO is also often the first indication of significant atherosclerosis, whose prevalence increased 35% from 1993-2007 (hcupnet.ahrq.gov). Current therapy, which attempts to increase retinal blood flow, has not improved outcome. Inner retinal ischemia is also, significantly, a final common pathway in major, chronic vision-threatening diseases including retinal vein occlusion and diabetic retinopathy (DR). With the increasingly aging population, DR is expected to increase 4-fold by 2050 (cdc.gov), a major health care burden affecting more than 10 million new US persons yearly. Elucidating the mechanisms that protect retinal cells in post-ischemic conditioning is paramount to the development of novel therapeutic strategies for the management of retinal ischemic disorders.
Dimitra Skondra, MD, PhD
Role of Gut Microbiome in Age Related Macular Degeneration
Age-related macular degeneration (AMD), the leading cause of irreversible blindness among adults over 50, is a multifactorial disease in which aging, genetics and environmental factors like diet play important role. The mechanisms by which these interact remain unknown. Understanding these interactions is crucial for the development of preventative and curative treatments. Gut microbes play a key role in human health and disease and are significantly affected by diet and environmental factors but their role in eye diseases is unknown. The goal of this innovative proposal is to study if gut microbiota could be the common denominator that connects lifestyle/environmental factors like high fat diet with AMD development. We will investigate how gut microbiota changes affect retina biomarkers and correlate with high fat diet. This approach will help uncover mechanisms causing AMD and could provide a new breakthrough insight into new treatment targets and strategies to prevent blindness in our community.
Utilizing Optical Coherence Tomography Angiography (OCTA) and visible light OCT in the at-risk patients with Non-arteritic Anterior Ischaemic Optic Neuropathy (NAION)
Non-arteritic anterior ischemic optic neuropathy (NAION) is the most common cause of sudden optic nerve-related blindness in the United States. However, the exact changes in the eye structure underlying this debilitating condition have not been worked out. Documenting the mechanisms that underlie NAION is therefore crucial to the development of novel clinical strategies that can both detect and treat this condition.
Immunotherapy of Dry Eye Disease with Probiotic Bacteria
Dry eye disease (DED) is a common condition that currently affects over ten million people worldwide. This condition results in symptoms such as eye irritation, eye dryness, and pain in the eye. Multiple studies have shown that inflammation is the hallmark of DED. The inflammation is caused by activation of TLR-4 and the NLRP3 inflammasome. Our study hopes to show that Lactobacillus rhamnosus will decrease the amount of inflammation caused by DED and promote corneal epithelial cell survival by inhibiting the activation of those inflammasomes.
Tejabhiram Yadavalli, PhD
Understanding the role of Heparanase in Herpetic Keratitis
Herpes simplex virus type-1 (HSV-1) induced keratitis is one of the main causes of infectious blindness in the USA. Currently prescribed drugs such as nucleoside analogs, acyclovir and its derivatives, ganciclovir and foscarnet, can cause severe side effects including renal failure, fetal abnormalities, and fail to prevent emergence of drug-resistant viral strains. In this proposal, our goal is to uncover novel pathways involved in the HSV-1 entry, replication and egress which can lay foundation to new drugs that target these pathways to curb infection. We have previously shown that Heparanase (HPSE), a host enzyme, plays an important role in the HSV-1 life cycle by facilitating viral egress from the infected cell. However, we believe that this enzyme has broader consequences during infection that previously thought. Hence, in this proposal, we would like to extend our study to understand underlying pathways which govern HPSE expression during HSV-1 infection. Given that HPSE plays an important role in ocular health, the findings from our project will help many researchers identify novel treatments against ocular infections/diseases in the long run.
A novel acellular porcine corneal stroma derived hydrogel (APCSH) for corneal blindness
Corneal disease is the fourth leading cause of blindness. However, in deep corneal ulcer or perforation, there is currently no standard treatment. Treatments currently include covering the corneal wound with corneal graft, amniotic membrane (AM) or glues. However, the corneal transplantation is limited by the availability of donors and the lifelong risk of graft rejection. AM or glue are only temporary solutions or induce incomplete healing. We have demonstrated previously that acellular porcine corneal stroma is a favorable biomaterial for corneal regeneration. By eliminating corneal cells and antigens by decellularization, this biomaterial present high biocompatibility, biomechanics and transparency in vitro and in vivo. In this project, applying this technique will allow us to develop an acellular porcine corneal stroma derived hydrogel. After optimizing its production and evaluation in vitro, this portable and injectable biomaterial may promote corneal healing and eliminate need for transplantation in future.