Week in Review: Number 2

Technique for Uniform Integration of Retinal Cells
Regenerating the retina and the optic nerve is one of the holy grails in ophthalmology, an endeavor that is still in the nascent phases of study and investigation at this point. The current study by Johns Hopkins Medicine researchers, using mouse retinas in vitro, illustrates an important obstacle to that goal: how to integrate the stem cells (retinal ganglion cells derived from human embryonic stem cells in this case) uniformly. In most cases, the many layers of the retina present a challenge, resulting in clumping of the cells. You can think of them as teeny, tiny tumors. The research team found, however, that areas of their in vitro retina model that were breached by incision showed more uniform integration of the retinal ganglion cells. They hypothesized that the internal limiting membrane (ILM), the innermost layer of the retina composed of footplates of Müller cells, could be the limiting factor. After loosening the ILM with an enzyme and removing it, the researchers found more normal integration of the retinal ganglion cells and establishment of new connections to the rest of the retina. This is one of those studies that seems obvious in hindsight. It makes sense that the ILM would present a barrier. So what was interesting was to see the process unfold of what would happen once the ILM was removed.

Toward Reliable Algorithms
Using artificial intelligence to screen retinal diseases is a promising line of research, with many software algorithms currently in development. The utility of this technology lies in its ability to accurately and reliably detect early disease states, a goal that is constantly improving. The current study examined the effectiveness of seven artificial intelligence (AI) algorithms in the detection of diabetic retinopathy, a common ocular complication of diabetes that could lead to vision loss. The algorithms were compared with human screeners in a teleretinal screening system, and both of these were compared to the standard of diagnostic expertise of retina specialists. A strength of the study is its sample size of nearly 24,000 images, from two VA health systems in this case. The researchers found much inconsistency between what is advertised of the algorithms and their performance in real-world clinical settings, with only one of the seven algorithms studied performing as well as the human screeners. This study is especially interesting for two reasons: (1) It highlights the importance of developing consistent methods in the diagnostic tool kit; conclusions can only be reliable if the methods are reliable. (2) Because this study is a kind of meta-analysis of several algorithms, it demonstrates the value of examining a broad range of information sources to arrive at the most robust method available. Note that through the examination of seven different algorithms, one was discovered to be as reliable as the human screeners, for the particular populations under study.

Air Pollution Risk in AMD
This observational study from the U.K. investigated the correlation between air pollution and increased risk of age-related macular degeneration (AMD), using both subjective and objective measures. The sample size is exceptionally large, comprising 115,954 UK Biobank study participants, who completed self-reported surveys of their AMD diagnosis, as formally diagnosed by a doctor. Among these participants, 52,602 were also assessed of retinal changes via optical coherence tomography (OCT). Estimates of ambient air pollution were from the BioSHaRE-EU Environmental Determinants of Health Project, and matched with official geographic data. In short, this is a robust observational study. The researchers found that people in the most polluted areas were at least 8% more likely to report having AMD. While observational studies cannot confirm cause, the results are not particularly surprising. Previous research, for example, identified smoking as a risk factor for AMD. Air pollution can be thought of as widespread ambient-level "smoking." Again, while the research team caution that observational studies cannot investigate mechanism, they suggest that ambient air pollution could be associated with AMD through oxidative stress and inflammation. Though the results are not unexpected, nor preventable given the ubiquitous challenge of air pollution, this study is a good example of a robust observational study, and highlights the benefit, perhaps even the need, to work toward better air quality for better health.

Ciliary Body as "Niche" for Eye Tissues
This study is interesting for two reasons. Firstly, the ciliary body is not as commonly talked about, unless you specialize in glaucoma, in which case it is talked about a lot. The ciliary body produces aqueous humor, a filtrate of blood, that nourishes the tissues of the eye. Glaucoma is a very complex disease with many contributing factors and consequences, but where the ciliary body is concerned, if too much aqueous is produced, it can lead to elevated intraocular pressure and damage to the optic nerve and other tissues (i.e., glaucoma). This study doesn't take the perspective of the ciliary body's connection to glaucoma though. Rather, it examines the ciliary body as a potential "niche" for eye tissues. The researchers themselves hesitate to call it a reserve for "stem cells," since previous research had disproved that hypothesis. However, they promote the hypothesis of a more indirect role of the ciliary body in maintaining eye tissues by means of the Notch signaling pathway. The details of the involved proteins are described in the article, but the synoposis is that the Notch pathway provides signals that affect the cellular morphogenesis and function of other eye tissues. In other words, the ciliary body doesn't provide the stem cells themselves, but rather regulates development of eye tissues through a signaling pathway. Finally, the research also explored how these proteins are involved in the functioning of the ciliary body itself.

Vision Testing for Early Detection of Parkinson's
The eye is the window to the soul, and also to neurological and systemic health, sometimes quite literally. Earlier in my training, I used to be amazed that funduscopy could detect cardiovascular disease, and then I was amazed that OCT could detect neurological diseases like Alzheimer's. Then the list grew and grew of what this window and this most valued function could allow us to see. The current studies, for example, correlate vision testing with new MRI scanning techniques in the early detection of Parkinson's-related cognitive decline. The connection is very indirect, but the research team found that Parkinson’s patients with visual dysfunction had more decoupling (for our purposes, an MRI-related measure) in memory-related regions in the temporal lobe. Both studies have small sample sizes, of 77 and 88 people with Parkinson's disease. And the connection is very indirect and limited at this point. That being said, with further development, early detection of Parkinson's disease via vision testing is encouraging.