Week in Review: Number 24

Contactless Robotic Optical Coherence Tomography
Scientists developed a fully automated ocular coherence tomography (OCT) system that captures a three-dimensional image of the entire eye, including an active-tracking scanning head that aligns itself with the patient's pupil as well as the ability to safely distance operator and patient. The system builds off of earlier work in intraoperative OCT and handheld OCT from colleagues within their institution, now adapted for physical distancing challenges posed by the COVID-19 pandemic. For example, the present iteration of a robotic OCT foregoes the need for chin and forehead rests for stabilization, relying instead on two sets of cameras that track the face and pupil, moving with patient movements to compensate for subtle motions. Additionally, as a comfort feature, patients use a foot pedal to control the robotic arm; when the patient takes his/her foot off the pedal, the robot moves away. A contactless OCT imaging modality also improves accessibility for patients with mobility difficulties, such as children and those who are wheelchair-bound. Advancements in the optical design of this system include working on a wider depth of field and the ability to visualize both the anterior and posterior segments of the eye simultaneously, capturing the entire eye in 3D. The ultimate goal of the project is to provide a one-to-one exact digital replica of the eye, which would enable studies related to the shape of the eye. They are testing applications of the technology in people with elevated intracranial pressure as a potential substitute for more expensive MRIs or more invasive spinal taps. The robotic design of the system should also facilitate telemedicine, since the robot can be sent to rural settings to capture images, the interpretation of which can be done by eye doctors remotely. The investigators report that early results of their system are encouraging both in terms of patient satisfaction and accuracy compared to traditional OCT.

OCT Angiography to Monitor Sickle Cell Retinopathy
Researchers developed a new technique using optical coherence tomography angiography (OCTA) to evaluate progression of sickle cell retinopathy before symptoms manifest as well as assess the efficacy of pharmacological treatment over time. OCT angiography is especially useful in monitoring of sickle cell disease, an inherited red blood cell disorder, in the sense that the visualization of blood flow can detect areas where the sickle-shaped cells clump together and cause local vascular damage, potentially leading to ischemia or hemorrhages. Their study involved 27 participants, 14 of whom were controls and 13 of whom had sickle cell disease with retinopathy of varying severity; some were on standard therapy (hydroxyurea) and others were not on treatment. The series of OCTA scans showed, unsurprisingly, that healthy participants had consistent blood flow with no or very minimal fluctuations. The untreated sickle cell patients, however, had substantially more intermittent vaso-occlusion (more flickering between scan images) than patients on treatment, indicating that treatment was effective. The investigators then used a computer algorithm to assess risk of retinal blood blockages based on flicker frequency and locations of flickering. The lead investigator explains, “We have added a new dimension to ocular imaging technology that no one has thought of before. For the first time, we have shown that by doing rapid, repeated retinal imaging of sickle cell patients, you can see microscopic changes in blood vessels and blood flow. The more the blood flow fluctuates across images, the more at risk patients are for a permanent blockage, which severely damage their eyesight.” The early detection of retinopathy in asymptomatic sickle cell patients could prevent irreversible vision loss when it's too late. Additionally, given a multitude of pharmacological treatments for sickle cell disease, monitoring the effectiveness of a particular drug regimen with OCTA can better inform the choice of drugs.

Case Report: Fundus Albipunctatus Diagnosis Using Adaptive Optics SLO and Genetic Testing
Investigators presented a rare case of a 62-year-old man who was misdiagnosed with Stargardt's disease for ten years before adaptive optics scanning laser ophthalmoscopy (AOSLO) and genetic testing revealed a diagnosis of fundus albipunctatus. Much rarer than Stargardt's macular dystrophy, fundus albipunctatus is an inherited retinal disease categorized under congenital stationary night blindness (CSNB) that is associated with fundus findings. In fundus albipunctatus, an autosomal recessive mutation in the RDH5 gene disrupts proper retinoid recycling. Also unlike the progressive retinal deterioration seen in Stargardt's disease, the clinical course of fundus albipunctatus does not change over time. While a diagnosis of fundus albipunctatus is confirmed with genetic testing, AOSLO was helpful in explaining the patient's clinical presentation and characterizing the photoreceptor status of the disease. The investigators explain, "Previous studies using AOSLO in Stargardt’s disease have revealed increased cone and rod spacing, with reduced foveal cone density and enlarged cone size, and dark cones thought to be associated with foreshortened outer segments. These findings are similar to our patient’s photoreceptor characteristics on AOSLO, except for the profound sparing observed in the central fovea." The use of AOSLO to characterize the cellular structure of photoreceptors in a patient with fundus albipunctatus revealed that in the later stages of the disease, some structures of photoreceptor cells were preserved, advancing understanding of the condition for future gene therapies. While fundus albipunctatus currently has no cure, earlier detection can inform better genetic counseling for family members as well as better counsel patients regarding the prognosis of the condition.

Nano-SOD1 Antioxidant to Treat Ocular Inflammation
A team of Russian scientists, along with American colleagues, developed an anti-inflammatory drug specifically for the eyes, which they tested in vivo in a rabbit model of uveitis. Their project involved creating multilayer polyion nanoparticles of the superoxide dismutase enzyme (Nano-SOD1), with a new formulation specifically manufactured for topical use on eyes. Superoxide dismutase is among antioxidant enzymes that are potent scavengers of reactive oxygen species (ROS), the excessive production of which during cellular processes leads to inflammation and tissue degeneration. When this inflammation occurs in ocular structures that are intricately arranged—such as the cornea, the lens, and the retina—the subsequent tissue damage can lead to blurred vision and even vision loss. While superoxide dismutase is an effective antioxidant, its very limited permeability presents a challenge for drug delivery to the eye, a relatively isolated organ that is often preferentially treated locally rather than systemically. As seen in their rabbit model of immunogenic uveitis, one of the authors states, "It was shown during preclinical studies that topical instillations of Nano-SOD1 were 35% more effective in reducing the manifestations of uveitis compared to the free enzyme SOD1. In particular, we noted statistically significant differences in such inflammatory signs of the eye as corneal and conjunctival edema, iris hyperemia and fibrin clots." The authors also report improved penetration into interior eye structures, longer retention of enzyme activity, and greater antioxidant activity for Nano-SOD1 compared to SOD1 by itself. So far, Nano-SOD1 shows a good drug safety profile at wide concentration ranges and at extremely high doses. Preclinical trials continue to explore its potential as a therapeutic agent for the treatment of ocular inflammation.

Transparent Diffractive Corneal Inlay for Presbyopia
As part of a doctoral thesis, researchers in Spain designed the first transparent diffractive trifocal intracorneal inlay as a potential treatment option for presbyopia. Consisting of an extremely thin (less than 5 microns) lens made of a biocompatible material, the corneal inlay would be placed inside the corneal stroma in a cavity created with a femtosecond laser. According to the research team, the lens is micro-perforated to allow the flow of nutrients within the cornea and to reduce the likelihood of rejection, and its transparent design does not prevent retinal examination. Like existing trifocal refractive technology, this corneal inlay corrects for vision at far, intermediate (computer range), and near vision. However, the authors highlight that the main novelty of this corneal inlay is that it uses a diffractive lens, as compared to existing small-aperature corneal inlays and refractive corneal inlays. One of the researchers explains, “The first type produce an extension of the depth of focus with which intermediate vision is gained but their luminous efficiency, since it is partially opaque, is low. The second type achieve[s] bifocality, so it has a good performance for nearsighted and farsighted individuals, although it loses quality at intermediate distances. Our design, according to the tests we have developed, overcomes all these handicaps.” Additionally, they state that their corneal inlay is fully compatible with other laser refractive surgeries as well as subsequent cataract surgery. The tests the team performed compared their design with another model currently used in clinical practice using commercial optical design software and subsequently on an artificial eye with an optical simulator. Their next step is to test the design in non-invasive clinical trials.

In Other News
(1) Get the best eye care during COVID-19
(2) Healthy vision development begins from birth
(3) Eye conditions on the the rise during the pandemic (Related)