(Dark) Adapting to research in India

Imagine you’re driving home late at night. You’re minding your own business when suddenly, you’re startled by another car’s high beams as the driver zooms around a corner. While grumbling to yourself about the other driver’s lack of consideration, you return your focus to the dark road ahead of you. You’re disoriented for a few moments and experience difficulty perceiving details. If you’re an individual with relatively healthy eyes, you will gradually “dark adapt” back to your surroundings when the peripheral photoreceptors in your retina adjust. It is primarily rod photoreceptors that allow us to see in low light, or scotopic conditions. We have a sensitive pigment in our rods called rhodopsin, which detects visual signals in the dark that can be sent to the brain. When rhodopsin is “bleached” or hit with high intensity light, the rhodopsin is temporarily non-functional and the cones will try to take over. Though they adapt faster than rods, cones are generally not as sensitive in dark conditions, which explains this temporary “blindness.” This delayed transition doesn’t cause major problems when you’re walking from a sunny parking lot into a movie theatre, because your rods have some time to adapt to the darkness. When you’re driving at high speeds, however, you don’t have several minutes or a half hour to allow your rods to fully adapt after being exposed to a bright light. Herein lies a problem with driving at night. The transition from dark to bright to dark again occurs rapidly with passing cars, and your rods don’t have a chance to catch-up after becoming bleached. In someone with a retinal degenerative condition, vitamin A deficiency, or other deficit, this transition might occur very slowly or not at all. These individuals are identified as being nyctalopic, or night blind. 

You might have been able sense my excitement about a test called FST in my last post. To recap, FST stands for “Full Field Stimulus Threshold Testing”, and it’s a psychophysical measure of someone’s visual threshold in scotopic conditions. The premise of the test involves dilating and ‘dark adapting’ someone for about 40 minutes, meaning they sit in a completely dark room so that their rods grow accustomed to the dark conditions. A full field flash of light is administered at a wide range of intensities, and the built-in algorithm uses forced-choice responses to calculate a probability of detecting a certain threshold of light. Although it sounds simple, this ‘subjective’ test is able to detect responses from the most sensitive parts of the retina. While FST does not provide a spatial assessment of vision like ERG does, its distinct advantage is that it can pick up responses in low vision individuals or patients who have severe rod dystrophies. Additionally, it is not uncomfortable for the patients and it’s faster than other methods. The examiner can use different wavelengths of light (which appear as red, blue, or green) to test rod and cone sensitivity in greater detail. Aravind had the necessary equipment in place but lacked certain tools required to complete the test, something that I have been able to work with them to implement using my research funds. 

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Aravind is a particularly special place to be able to use FST due to the magnitude of patients with nutritional, genetic, and disease-related retinal abnormalities. Patients regularly come to the retina clinic with Retinitis Pigmentosa, Leber Congenital Amaurosis, and Stargardt’s disease, among many other diseases. The seemingly most common condition patients present with, unsurprisingly, is diabetic retinopathy (DR). DR is a leading cause of blindness, affecting 93 million people across the globe.¹ The Times of India referred to India as the ‘diabetes capitol of the world’, with approximately 50 million people living with Type 2 Diabetes. Poor disease management is the norm as shown by many of these patients, and uncontrolled blood sugar is a major contributor to worsening ophthalmic health. Although excellent research has been completed over the past few decades in order to describe DR pathogenesis in animal and human models, the results in some areas are incomplete. One such area is dark adaptation. There is a small yet interesting body of literature pertaining to dark adaptation studies and DR, and I am hoping to contribute additional characterizations of photoreceptor function in different cases of DR using FST.  

In the introduction to this post, I talked about driving as one specific danger of dark adapted deficits, however night blindness can affect an individual’s quality of life and safety in other ways. Because patients with DR experience peripheral retinal changes even early on in disease progression and they undergo procedures that can salvage day vision and harm night vision, they are an ideal population for FST testing. In addition to clinical outcomes, it is important for patients to be aware of diagnosed dark adapted deficits in order to avoid high risk activities. I’ll talk more about our specific studies in my next post! 

This is the first time I have been able to conduct research with real people using my own ideas. I love doing clinical research in the U.S., but my role is different in that I am executing the protocols and ideas of my superiors, not my own. Although it is exciting to have autonomy over a project, it comes with a new set of elevated responsibilities. Luckily, I have excellent mentors in India and in the U.S. to guide me through these challenges. I’m working with the chief of Aravind’s retina department, Dr. Pankaja Dhoble, an inspiring and passionate physician. As someone who has extensive research experience, she is showing me how to push the research process forward in a country where punctuality and deadlines are sometimes neglected. The IRB and patient recruitment processes are also quite different from what I have grown accustomed to in the U.S., yet some of the challenges of clinical research appear to be universal. I was warned that following up with patients in India can be difficult and time consuming, something I am all too familiar with in our studies back at home. Despite these obstacles, human research is incredibly rewarding and offers the unique opportunity to connect patients from diverse backgrounds with innovative diagnostic tools. I cannot wait to move forward with our work over the next few weeks and I’m even more excited for our collaboration that will continue over the next year. 

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A Mid Level Ophthalmic Personnel (MLOP) testing our program in the dark room!

Global prevalence and major risk factors of diabetic retinopathy.Yau JW, Rogers SL, Kawasaki R, Lamoureux EL, Kowalski JW, Bek T, Chen SJ, Dekker JM, Fletcher A, Grauslund J, Haffner S, Hamman RF, Ikram MK, Kayama T, Klein BE, Klein R, Krishnaiah S, Mayurasakorn K, O’Hare JP, Orchard TJ, Porta M, Rema M, Roy MS, Sharma T, Shaw J, Taylor H, Tielsch JM, Varma R, Wang JJ, Wang N, West S, Xu L, Yasuda M, Zhang X, Mitchell P, Wong TY, Meta-Analysis for Eye Disease (META-EYE) Study Group Diabetes Care. 2012 Mar; 35(3):556-64.

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About oliviamhess

I interned at Aravind Eye Hospital-Madurai as a CASI Student Programs Intern in 2015, and I am returning to Aravind in Pondicherry to conduct research using CASI Summer Travel Funds, the Association of Alumnae Rosemary D. Mazzatenta Scholars Award, and the Gelfman International Summer Fund.