Research studies have a multiplicative power to extend beyond their initial size. Descriptions of newly recognized, rare diseases may present 10 cases and provide information that can be generalized to the 100 or 1000 people that may have that similar condition. Larger epidemiologic studies examine thousands of patients and are generalizable to millions or even billions of people. By virtue of their large sample size, it is possible for big epidemiologic studies to find numerous statistically significant associations. However, the statistical significance of these associations as expressed by P values does not necessarily mean the magnitude of the association is significant in a clinical setting.
An important article in this issue, “Visual Acuity and Subfoveal Choroidal Thickness: The Beijing Eye Study,” reports analysis of 3233 subjects. Visual acuity was found to be significantly associated with subfoveal choroidal thickness ( P < .001) and in particular a choroid thicker than 30 μm ( P < .001). Additional factors that were significant, and also controlled for in the regression equation, included younger age, higher level of education, taller body stature, higher body mass index, thicker subfoveal choroidal thickness, absence of glaucoma, absence of diabetic retinopathy, absence of the late stage of age-related macular degeneration, and axial length shorter than 26.0 mm.
We can parse through these factors and try to determine possible explanations for the results. Young people are less likely to have advanced forms of pathologic myopia, age-related macular degeneration, and glaucoma. Absence of these ocular diseases would be expected to be related to better vision on average as compared with a group with these diseases. Taller body stature and higher body mass index are indicative of better nutrition and, in all likelihood, higher levels of income with its inherent improved access to health care; this may also apply to higher levels of education. That leaves a most interesting feature for last, the subfoveal choroidal thickness as measured by optical coherence tomography.
The possibility that the observed correlation occurred by chance alone is unlikely because of the high level of statistical significance and the ability to parse out a group (those with particularly thinner choroids) that had poorer acuity. It is possible that the observed correlation is secondary to some unknown and unmeasured factor related to the 2 variables that actually were measured. Maybe the correlation suggests an important link that deserves further investigation. Could there be a biologically plausible reason for choroidal thickness to be related to visual acuity? The choroid is so replete with vessels that it seems difficult to understand how a small change in thickness one way or another could affect visual function.
Is the Choroid Overspecified?
In engineering design a structure or component can be designed to exceed the stresses found in day-to-day use. For example, a building may be designed so that the structural elements, such as the beams or floors, are capable of supporting much more weight than they are really expected to handle. This difference is called overspecification. The excess capacity may allow the building to safely survive an earthquake or storm. The probability and severity of these external events can be factored into the design process. The downside of overspecification is excess cost from using scarce resources that could be devoted to other purposes.
The choroid has the highest blood flow and densest packing of vessels of any tissue in the body and has the lowest oxygen extraction. Other tissues in the body extract much of the oxygen carried by hemoglobin, and those tissues seem to do just fine. Looking at these simple parameters suggests that the choroid may have a capacity greatly in excess of what it really needs. So how could a thinner choroid make any real difference in function? Simplistic analyses are often wrong—after all, there are so many streets in Manhattan that there should never be a traffic jam. Although only 1% of the oxygen is extracted from the blood, there is an enormous flux of oxygen delivered to the outer retina. The oxygen delivered by the choroid is used by the mitochondria in the inner segments to generate energy for the photoreceptors. In the dark the oxygen tension of the outer retina falls to zero. Only 20% of glucose used by the photoreceptors is oxidized to produce energy. The remaining 80% undergoes glycolysis to generate energy above what can be made by aerobic metabolism. The heat generated in this subcellular band needs to be taken away, and one important function of the choroid may be to act as a heat sink.
When we climb a mountain the first and most memorable sensations are the views. However, changes in scotopic vision can be demonstrated at altitudes of as little as 1500 meters. At altitudes of 2400 meters there are measurable decreases in mesopic visual function, and at 3050 meters (approximately 10 000 feet) abnormalities in photopic vision occur, including loss of acuity, color vision, and contrast sensitivity. The choroid does show some reserve in functional capability, as we can see when we are on the mountain, but even with small decreases in atmospheric oxygen tension visual function is not optimal. The question of overspecification also needs to be examined from an evolutionary standpoint. The last common ancestor that possessed a vertebrate-style eye, that is, one with the retina inverted, occurred about 420 million years ago. The eye across vertebrate species started with a common plan. Given that the evolutionary pressure for survival fine-tuned the eye across many divergent and oftentimes competing species in parallel, that all of them ended up with a design that includes a highly vascularized choroid suggests an anatomic optimum, at least for individuals through reproductive age.
We have very little knowledge of how choroidal thickness and delivery of oxygen are related. Even though the study by Shao and associates demonstrates a statistically significant change in vision with small decrements in subfoveal choroidal thickness, these changes are extremely small and, over the range of thicknesses seen in the general population, have no significant clinical utility. From the regression analysis by Shao, a 100 μm change in subfoveal choroidal thickness would result in an expected change of 0.007 logMAR acuity. Much more important was the finding of a threshold in subfoveal choroidal thickness where function shows a meaningful decline. A choroid thinner than 30 μm was found to be independently associated with a visual acuity loss of 0.31 logMAR—that is equivalent to a 3 line change in the commonly used Early Treatment of Diabetic Retinopathy Study acuity chart. This level of thickness may be seen in older individuals, is common in those with pathologic myopia, and is nearly universal in people with both. The magnitude of visual acuity change determined by Shao is very similar to the association found between acuity and thinner choroids in eyes with high myopia; the extension of this finding to eyes without high myopia increases the pool of patients likely to have vision loss related to a thin choroid. With increasing longevity worldwide coupled with the epidemic increase in high myopia, choroidal loss could easily become one of the most significant causes of moderate (and even severe) vision loss in the world.
The author has completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. R.F.S. is a consultant and receives royalties from Topcon Medical Systems, Inc. Supported in part by the Macula Foundation, Inc , New York, New York. Contributions of author: R.F.S. was responsible for all facets of this single-author text.