I was recently reading an interesting article from 2011 describing the story of how fluorescein angiography was brought to our field by a couple of medical students in late 1950s in Indiana. The article (Marmor et al.) was full of fascinating tidbits like how the students were yelled at for “violating” an expensive camera with their filters, how they used their girlfriends as some of the first test subjects and how even after that amazing start to their ophthalmic education one student ended up choosing psychiatry as a career.
They didn’t know the spectral properties of fluorescein, so they injected the dye into samples of their blood and sent it to Eli Lilly and Co. to determine the adsorption and emission curves. Then they found some filters made by Kodak that “perhaps fortuitously” had peaks at 490 nm and 520 nm, with little overlap at 500 nm. The point here is that there were so many barriers to these students succeeding, but still they persevered and achieved their goal.
So it’s been about 60 years since fluorescein angiography (FA) arrived on the scene. It’s been fabulously improved upon, but the concept remains close to the same as the original.
What’s new in this field? The first thought that comes to mind is OCT angiography. We first discussed this concept 3 years ago, and the field of OCTA has only improved since then. OCTA has been discussed a lot in the field, and there is a lot more to come out of this interesting and early technology. But in comparison to FA, there are pros and cons to OCTA.
One of the benefits of OCTA is the depth of capillary imaging. FA will visualize only the superficial retinal capillary vasculature, losing out on the detail of the middle and deep capillary plexi that is now being studied in detail with new conditions like paracentral acute middle maculopathy. OCTA will have a tighter visualization of the foveal avascular zone even in leakage, unlike FA, where leakage can obscure the detail. And of course the biggest advantage OCTA has over FA is that it’s faster to obtain and noninvasive.
FA, however, has better sensitivity detecting low-flow lesions like microaneurysms and polypoidal lesions. And one of the best advantages of FA is the ability to capture a much wider area compared to OCTA. The largest scanning area of a commercially available OCTA is 8 mm x 8 mm, which is about 30 degrees. Now this will probably improve with time, but it will likely take a long time to achieve what you can do today with a nonmontaged widefield FA of 55 degrees to 120 degrees and ultra-widefield of up to 200 degrees.
Speaking of ultra-widefield angiography, this field is relatively new and yielding a lot of interesting findings. Far peripheral retinal pathology can be imaged with angiography, which is especially important in pediatric retinal diseases like Coats’ disease, familial exudative vitreoretinopathy and retinopathy of prematurity. Traditional FA in the periphery needs a skilled photographer and a cooperative patient, and the latter is a challenge in pediatric (or many!) patients.
And don’t forget there are other ways to image the retina that don’t involve the use of the fluorescein molecule. Molecular imaging is relatively new to being used for retinal disease, but positron emission tomography (PET) is a type of molecular imaging that’s been used for years to visualize metabolic processes in the body. There is work being done by one group to use molecular imaging to detect inflammation in the endothelium of retinal blood vessels (Sun et al.), and by another to check for retinal ganglion cell apoptosis (Capozzi et al.), just to name a few.
The point of all this is to say we need to be more like those two medical students in Indiana in the 1950s: We need to think outside the box. We need to be willing to break a couple cameras or turn our girlfriend’s skin (temporarily) orange in the name of science. Get out there and push some boundaries. Carpe diem.
Calvo CM, et al. Int J Retina Vitreous. 2018;doi:10.1186/s40942-018-0122-2.
Capozzi ME, et al. J Ocul Pharmacol Ther. 2013;doi:10.1089/jop.2012.0279.
Inoue M, et al. Retina. 2015;doi:10.1097/IAE.0000000000000777.
Marmor MF, et al. Arch Ophthalmol. 2011;doi:10.1001/archophthalmol.2011.160.
Sun D, et al. The FASEB Journal. 2010;doi.org/10.1096/fj.09-148981.