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Katrina Norfleet
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Posted: 5/10/2017
Emerging trends and hot topics: Presented Wednesday, May 10 at the ARVO Annual Meeting 
 

Baltimore, Md. ― In their own words, First Authors at the 2017 Annual Meeting of the Association for Research in Vision and Ophthalmology explain their findings. Their abstracts were designated as some of the newest and most innovative research presented on Wednesday, May 10, 2017.

Anatomy and Pathology/Oncology
#443 - 4427 - A0405. Time course of axial length changes in response to competing episodes of myopic and hyperopic defocus. 11am.
Nearsightedness (myopia) is a common vision problem which is increasing in prevalence. Myopia occurs due to excessive growth in the size of the eye during childhood and if it progresses throughout life it can lead to serious harm to the health of the eye and vision.

Research has shown that eye growth and size can be influenced by lenses that focus the light at different distances in the eye. During every day activities, the eye receives a series of focus signals from objects in our 3-D world. So how does the eye size change in response to this mixture of focus signals?
We exposed the human eye to a sequence of focus signals using optical lenses, and measured how the size of the eye changed over 60 minutes. We found that the eye responds to changes in focus rapidly (within minutes) with small changes in eye size. The eye becomes slightly longer when the focus is positioned continuously behind the eye, but with a mixture of focus signals in front and behind the eye, it doesn’t become longer. These findings will help us as we try to find optical methods to control eye growth and myopia progression in children.

#443 - 4429 - A0407. A 3D MRI study of the relationship between eye dimensions, retinal shape and myopia. 11am.
This study investigated the effect that being short-sighted has on overall eye size and on retinal shape (shape of the back half of the eye). Magnetic Resonance Imaging, or MRI, was used to measure eyes of young adults of different races. With short-sightedness increase, eye dimensions increased in all directions such that increase in length was considerably greater than increases in width and height. Eyes of normal sighted people had a shape in which the back of the eye was slightly squashed, but this was less obvious as short-sightedness increased and in eyes with quite strong myopia the shape was usually round. Females had smaller eyes than males, with overall dimensions being about 0.5mm less. Race did not appear to affect shape or size. These results are of interest in helping us to understand the development of short-sightedness and how it may be prevented or its development slowed.

#443 - 4439 - A0417. Quantitative 3-D OCT ocular geometry of lens-treated myopic and hyperopic guinea pig eyes. 11am.
Newborn eyes are generally long-sighted, but during growth the eye balances optical changes with its increasing length to achieve normal vision. This process is called emmetropization and is visually guided. In the presence of a degraded image quality this tuning mechanism fails resulting in short-sightedness (myopia).
In recent years, myopia has increased alarmingly worldwide. While visual blur experience plays a major role in myopia development, and causes excessive eye growth, the impact of abberant visual experience on other components of the eye have not been thoroughly investigated.

Animal experiments allow controlled manipulation of visual experience and show that negative and positive lens-wear causes the eye to compensate for the induced blur by increasing or slowing its growth respectively. In the current study, we demonstrate that changes also occur in the eye’s optics. Specifically, for the first time, we obtained three-dimensional images of myopic and hyperopic eyes in the guinea pig model using a custom quantitative OCT system. Interestingly, we observed curvature changes in the corneal and crystalline lens surfaces resulting in astigmatism, higher-order irregularities and spherical aberration. These data offer further insight into the changes that abberant visual input causes in the eye during the development of myopia.

Biochemistry/Molecular Biology
#445 - 4487 - B0142. Fundus Autofluorescence Analysis of the Transition Zone in Choroideremia: Outcomes Following Gene Therapy. 11am.
The worse-seeing eyes of six research subjects with choroideremia, a sex-linked progressive eye disorder, were treated with an injection of a virus that contains the correct version of the gene. One year later, the remaining supporting cells in all injected eyes continue to decay at the same rate as that of the fellow untreated eyes. Subjects will continue to be followed each year to determine whether gene therapy can modify or not the natural history of this disorder.

#445 - 4493 - B0148. Structural Modelling Predicts Variability in Efficacy of Lead Candidate Hammerhead Ribozyme Between Different Species Rhodopsin mRNA. 11am.
Scientists have developed a mathematical model to predict the success of gene therapeutics in early stages of development. Because gene therapy is highly specific and targeted, standard practice of using non-human animal models for preclinical trial may not provide accurate information about dose and side effects that would affect human patients. This computational model is a great way to predict therapeutic success and decrease the amount of animals that would be used to evaluate developing gene therapies for visual disorders.

Eye Movements/Strabismus/Amblyopia/Neuro-Ophthalmology
#489 - 5090 - B0700. Development of an open-source pupilometer for testing melanopsin responses. 3:45pm.
Around 1% of our optic nerve cells are the fascinating melanopsin-containing retinal ganglion cells. In our patients, the function of these cells can be quantified by measuring the sustained pupil constriction that occurs in the dark after a very bright flash of blue light. Unfortunately, most researchers require electrophysiology equipment to measure this, which is not portable and costs > USD $50,000. We have developed an open-source 3D-printed device using cheap and widely available components, that can be produced by any interested scientists or doctors for around USD $100. There is potential for enhancing diagnostic decisions (in a range of clinical settings from ambulances to neurology clinics) and cloud-based data collection (creating a large biometric database). We are excited how open source technology democratizes interesting new clinical science.

#415 - 3838 - A0009. 3D Printing for Low-cost Rapid Prototyping of Eyelid Crutches. 8:30am.
3D printing can be an extremely useful tool for medical therapy. It can let healthcare providers quickly prototype and customize medical devices for patients. Our project involved a patient with severe ptosis in both eyes, or drooping of the upper eyelids. Although seemingly trivial, if ptosis is severe enough, the eyelid can obscure the patient’s vision and significantly impact quality of life, as was the case for our patient. Our patient had already undergone surgeries for ptosis correction, but because of her chronic underlying disease, her ptosis kept coming back. She was no longer a candidate for further surgeries and therefore needed another solution. An eyelid crutch was suggested as a non-surgical treatment. The crutch is normally attached to a patient’s eyewear frame and consists of a metal arch that contacts and helps raise the drooping eyelid. While the crutch is a simple tool, the costs and requirement of a specialized technician may be a problem for some patients. Thus we used 3D printing to design and make our patient customized eyelid crutches at a low cost. The crutches were successful and showed that 3D printing can be an effective part of patient care.

#414 – 3827. Binocular outcomes following binocular treatment for childhood amblyopia. 9:30am.
Amblyopia, commonly called lazy eye, emerges during childhood and has traditionally been treated with patching of the fellow eye to force use of the amblyopic eye. But patching does not always restore normal vision and can be uncomfortable for children. More importantly, patching does not teach both eyes to work together. Recently, researchers have assessed a new method of treating amblyopia that involves viewing movies or playing iPad games with BOTH eyes while wearing special glasses. The key is that high contrast (sharp) images are sent to the amblyopic eye and low contrast (faded) images are sent to the fellow eye, allowing both eyes to work together during treatment.

The current research showed that this new binocular amblyopia treatment was effective in improving visual acuity after 2 weeks, and this improvement was better than patching for 2 weeks. Vision outcomes that measure the ability of the two eyes to work together (i.e., binocular outcomes), such as stereoacuity (depth perception), and extent and depth of amblyopic eye suppression also improved with binocular treatment. These findings suggest that binocular treatments are effective at treating amblyopia and should be considered as an additional treatment option by clinicians.

Immunology/Microbiology
#437 – 4293. Corneal infections: targeted eradication through antibiotic functionalized polymers. 11:45am.
The cornea is a transparent structure at the front of the eye that helps to focus light. When damaged, the cornea can become infected causing pain, swelling and vision difficulties. Bacteria prefer to attach to damaged rather than healthy corneas and once attached they grow in a state called a biofilm. In a biofilm, bacteria are covered in a layer of protective bio-molecules which makes corneal infections difficult to treat with standard antibiotics. In our work, we designed a synthetic material, which is not harmful to the eye, but is able to bind and remove bacteria from the eye. Our material prevents the growth of biofilms and so could potentially help to improve the ability of standard antibiotics to eradicate infections of the eye.

Low Vision Group
#474 – 4764. eQUEST: The eSight Quality of life and Efficacy Study. 4:30pm.
eSight Eyewear is a hands-free, portable video device worn like sunglasses, designed to help the partially sighted achieve much better functional vision for all manner of daily tasks. This paper evaluates the findings of a six-site sponsored study by leading researchers in low vision rehabilitation. The primary tool used in the study was the well-validated VA LV VFQ48 “Visual Function Questionnaire”. Users showed statistically significant improvement in all visual function categories in all categories except mobility.

Preliminary analysis shows no strong correlations with age, diagnosis, or sex, indicating that the eSight device has potential across a broad low vision cohort.

Other measures included standardized visual function tests such as acuity measurement, contrast performance, and reading to measure how the device improved subjects’ performance in these areas. Additional customized tests were included to evaluate the device for specific tasks such as facial recognition proficiency, and various routine daily living activities. Results from these tests demonstrate that the eSight Eyewear device can provide significant improvement in all areas of visual function, and has the potential to substantially improve quality of life for the visually impaired.

Retina
#426 - 4160 - B0455. Repeated subretinal surgery and removal of subretinal decaline is well tolerated – evidence from a porcine model. 8:30am.
The retina is a thin sheet of cells lining the inside of the eye. When the eye looks at something the retina is the “camera-film” that transforms the seen images into signals the brain can understand. The retina can detach from its normal position, a disease known as retinal detachment. Left untreated retinal detachment cause blindness. The only treatment to save vision is to reattach the retina surgically. To flatten and push the retina back in place a heavy liquid is placed on top of the detached retina. If the heavy liquid unintended move under the retina the “camera-film” is permanently detached from its normal position. It will lead to visual loss if the heavy liquid is not removed from underneath the retina. We have found that it is possible to surgically remove decalin without damaging the retina in a pig model and that visual function is then maintained.

#426 - 4164 - B0459. The association between the frequency of rhegmatogenous retinal detachment and the atmospheric temperature. 8:30am.
Chorioretinal adhesion is important for the the normal retinal adhesion and affected by temperature. From the point of view that chorioretinal adhesion was affected by temperature, rhegmatogenous retinal detachment (RRD) frequency may be affected by temperature. Therefore, we investigate the association between the frequency of RRD and the atmospheric temperature.

The monthly average number of RRD operations showed a bimodal peak (April and October) throughout the year. With the same tendency as frequency of RRD, the monthly average of daily temperature range during 1 year also showed bimodal peak in April (daily temperature range, 12.3 ° C) and October (daily temperature range, 11.2 ° C). And there was a significant positive correlation between the monthly average of daily temperature range and the number of RRD surgery. However, there were no association between RRD frequency and mean temperature, highest temperature, lowest temperature.

From this study, we could know that temperature changes may affect the occurrence of RRD.

#404 – 3767. Controlled and Extended Release of Bioactive Aflibercept from a Biodegradable Microsphere-Hydrogel Ocular Drug Delivery System. 9:45am.
In this study, we investigated use of an injectable, biodegradable smart polymer drug delivery system to deliver anti-vascular endothelial growth factor (anti-VEGF) agent for treatment of wet age-related macular degeneration, and diabetic macular edema. One of the biggest challenges of anti-VEGF therapy is that in order to be effective, monthly or bimonthly intravitreal injections are needed for unknown period of time. The burden of repeated injections on patients, family and healthcare system is significant. Our drug delivery system is designed to release anti-VEGF in a sustained manner for over 6 months and is fully biodegradable. Our goal is to replace repeated monthly/bimonthly injections and increase efficacy and therapeutic results with our drug delivery system.

#433 – 4270. Behavioral and electrophysiological characterization of photovoltaic subretinal implants in non-human primates. 12:30pm.
Blindness results from the loss of photoreceptors in retinal diseases and age-related macular degeneration. Despite some restoration of visual sensation in blind patients, retinal prostheses were not able to restore face recognition or complex text reading. To reach these goals, we have here evaluated new modular high-acuity photovoltaic implants from Pixium Vision on living non-human primates. Using a task of eye movement, we showed that activation by infrared light is sufficient to induce visual perception following single pixel activation as fast as with natural light perception. The required energy is well below radiation safety limits compatible with human applications. This demonstration of a visual perception by these photovoltaic implants paves the way for their clinical evaluation in blind patients.

Retinal Cell Biology
#422 - 4044 - B0017. NFAT-dependency of IL-1β-induced diabetes-relevant behaviors in human retinal microvascular endothelial cells and Müller cells. 8:30am.
Scientists have identified a novel therapeutic target that may prevent the development of diabetic retinopathy. Diabetic retinopathy is the leading cause of blindness in working age Americans. Diabetics have a number of systemic issues like high blood sugar and chronic low-level inflammation that cause the blood vessels in the retina to breakdown. The retina is the part of the eye responsible for turning light into a signal for the brain so when retinal blood vessels breakdown, vision-threatening issues arise. The retina has a number of different cell types that respond to the diabetic environment by altering their behavior in a way that contributes to blood vessel breakdown. The scientists have identified a therapeutic target that could be used to prevent the pathogenic response of at least two different retinal cell types. Because this therapeutic target controls events early in diabetic retinopathy, it would prevent disease progression from irreparably damaging the patient’s vision.

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