Week in Review: Number 39

Self-Navigating Smart Cane for the Visually Impaired
Engineers at Stanford designed a self-navigating smart cane based on technology used in autonomous vehicles. The Augmented Cane not only helps people with visual impairments to detect obstacles using a LIDAR sensor, but is also equipped with software that controls a motorized wheel mounted at the tip of the cane to gently nudge users through their environment, including to specific destinations. Additionally, the cane relies on GPS to measure position in outdoor settings, an inertial measurement unit (accelerometers, magnetometers, and gyroscopes) to measure the user's position and orientation, and a camera to capture images of the surroundings. In real-world tests, use of the smart cane improved walking speed for visually impaired volunteers by 18% compared to the traditional white cane. For sighted individuals who were blindfolded, use of the smart cane improved walking speed by 35%. This smart cane is also an improvement over other research sensor canes in terms of weight and cost. Weighing only 3 pounds, the cane can be built at home from off-the-shelf parts and free, open-source software for $400. The research paper includes a downloadable parts list and DIY solder-at-home instructions. Although the Augmented Cane is still a research prototype, the researchers welcome input from industry to streamline the design and scale up production to make the smart cane even more affordable. They next plan to make refinements to the project, such as developing a model that uses an everyday smartphone as the processor to broaden access and further drive down cost. Senior author of the study comments, “Our lab is based out of the Department of Aeronautics and Astronautics, and it has been thrilling to take some of the concepts we have been exploring and apply them to assist people with blindness.”

High Resolution MRI of the LGN's Two Compartments
The thalamus is a relay station connecting sensory input to different regions of the brain. The visual sensory thalamus is a region that connects the eyes to the brain, with several nuclei that are involved in visual processing. The lateral geniculate nucleus (LGN) of the visual sensory thalamus, a nucleus that is most relevant to visual processing, contains two compartments, which are characterized by different amounts of white matter (myelin). Thus far, it has been difficult to assess these two compartments, because they are small and located deep within the brain. Neuroscientists in Germany are investigating a new noninvasive imaging method known as structural quantitative MRI (qMRI) using a specialised MRI machine with unprecedented high spatial resolution. By coincidence, a doctoral student noticed structures that she thought might resemble the two LGN compartments in neuroimaging data. She followed up the discovery with imaging of 27 participants with the 7 Tesla in-vivo qMRI and studying ultra-high resolution 7 Tesla qMRI of one post-mortem human LGN specimen. Along with histological confirmation, the results showed that differing amounts of white matter can be detected on the high resolution MRI images, demonstrating that this new imaging technique can be used to investigate the two compartments of the lateral geniculate nucleus in living humans. First author of the study comments, “The finding that we can display visual sensory thalamus compartments in living humans is fantastic, as it will be a great tool for understanding visual sensory processing both in health and disease in the near future."

SLT for Improved Glaucoma Care in Africa
Globally, glaucoma is the most frequent cause of irreversible blindness, with the highest prevalence and incidence in Africa, which also has the highest prevalence of blindness due to the disease. The only currently modifiable factor in the treatment of glaucoma is lowering intraocular pressure (IOP), which can be accomplished through eye drops, laser procedures, or surgery. Research conducted in Tanzania compared the use of beta-blocker timolol 0.5% eye drops and selective laser trabeculoplasty (SLT). Although the most affordable, and thus the most commonly used, glaucoma medication in lower income settings, timolol also comes with potential systemic and local side-effects and high long-term costs due to the need for daily life-long treatment of glaucoma. The study lead comments, “Glaucoma requires life-long treatment and follow-up to save a person’s sight, which can be very challenging in many settings. Currently, most people are treated with eye drops but many struggle with taking them regularly or accessing new bottles, for example due to cost or distance to the nearest clinic." An ophthalmologist at the hospital where the study was conducted adds, "[S]ome of the patients after sometime decide to ignore or just stop using eye drops. If we can establish an alternative effective means of arresting the disease, we would bring about a positive impact on the quality of life of these patients." The randomized controlled trial enrolled 201 patients (382 eligible eyes) with open-angle glaucoma and an IOP above 21 mm Hg, and did not have asthma or a history of glaucoma surgery or laser. Among the 101 patients assigned to the SLT group, 33 required two SLT procedures, while 66 were successfully treated with one SLT procedure. After one year, data from 339 eyes were analysed, showing that eye drop treatment was successful in 31.3% (55/176) of eyes, while SLT was successful in 60.7% (99/163) of eyes. The affordability of SLT was also considered, with the study suggesting that for hospitals that treat a high volume of glaucoma patients, SLT could be offered at a similar price as an annual supply of timolol eye drops. The researchers acknowledge that a longer follow-up period is needed to evaluate vision and quality of life; however, they stress that "studies such as these are crucial for identifying solutions that can tackle the challenge and improve the lives and livelihoods of those in Sub-Saharan Africa and beyond."

Injectable Treatment Targeting Schlemm's Canal Explored for Congenital Glaucoma
Primary congenital glaucoma (PCG) is a pediatric form of glaucoma that results from developmental defects in the trabecular meshwork (TM) and Schlemm's canal (SC). As with other types of glaucoma, this in turn compromises aqueous outflow, causing a build-up of intraocular pressure (IOP) that ultimately damages the optic nerve and leads to vision loss. Although rare, primary congenital glaucoma is devastating in its severity and early onset, with few viable treatment options other than surgery. Some scientists are working on a new class of injectable treatments. In this case, they genetically engineered mouse models that resembled forms of PCG. The authors write, “Recently, heterozygous loss of function variants in TEK and ANGPT1 or compound variants in TEK/SVEP1 were identified in children with PCG. Moreover, common variants in ANGPT1and SVEP1 have been identified as risk alleles for primary open angle glaucoma (POAG) in GWAS studies [genome-wide association studies]. Here, we show tissue-specific deletion of Angpt1 or Svep1 from the TM causes PCG in mice with severe defects in the adjacent SC.” Next, they administered intraocular injection of a protein called Hepta-ANGPT1, recombinant ANGPT1-mimetic, to replace the function of the mutated genes. They report that Hepta-ANGPT1 promoted developmental SC expansion in healthy and Angpt1  deficient eyes, and blunted IOP elevation and RGC loss in one mouse model of primary congenital glaucoma. When injected into the eyes of healthy adult mice, Hepta-ANGPT1 lowered intraocular pressure. They additionally performed single-cell transcriptomic analysis of normal and glaucomatous Angpt1  deficient eyes to investigate TM-SC signaling pathways. The authors highlight the role of ANGPT1-TEK signaling and TM-SC crosstalk in IOP homeostasis that could guide a potential new class of drug therapy for glaucoma that targets Schlemm's canal.

Submacular hESC-RPE Transplant in Macaques
Inherited retinal diseases (IRD) are estimated to affect 1 in 2000 people globally. However, the extent of heterogeneity in inherited retinal diseases, involving more than 260 identified genes, limits the widespread application of gene therapy, which is often specific to singular or related genes. Gene thereapy also has limited success in advanced stages of retinal degeneration, wherein significant photoreceptor death has already occurred. The advent of stem cell therapy, such as induced pluripotent stem cell (iPSC) and embryonic stem cell (ESC) therapy, provides an alternative route to treatment of retinal diseases through regenerative medicine, independent of the underlying genetics. There has been some success in visual improvement in smaller animal models following transplantation of retinal photoreceptor precursors, although the results are more limited in larger mammals. Researchers in Singapore are exploring the therapeutic potential of photoreceptor precursors derived from human embryonic stem cell (hESC)-derived RPE on a scaffold. The most recent experiments in 11 cynomolgus monkeys (macaques) showed "both structural and functional submacular integrations of hESC-RPE xenografts." In particular, microscope-integrated intraoperative (miOCT) typically revealed foveal disruption (trapped residual subretinal fluid), a negative outcome. However, electroretinogram (ERG) showed amplitude and peak time preservation in cases with favorable surgical outcomes, and histology confirmed photoreceptor preservation above the grafts and in vivo phagocytosis by hESC-RPE, i.e., active RPE function. Finally, the immunosuppression protocol was effective at suppressing retinal T cells and microglia. This is all to say that research in stem cell therapy for IRDs is still in progress. However, the researchers anticipate that refinements in technique will bring improvements to this area of therapy.

In Other News
(1) Heru adds 3 more diagnostics to VR headset-based vision testing platform
(2) A Rolex watch made using femtosecond lasers
(3) Trilobite fossil with unique compound eyes (Related)