Retinal Imaging: The Future is Bright with New Technologies

By John W. Kitchens, MD

Introduction
There have been certain major “eras” in ophthalmology. These could include: the phaco era, the refractive era, the anti-VEGF era, among others. I believe we are about to enter into “the imaging era”, specifically in regard to the management of retinal diseases. At no time in the history of ophthalmology have more companies come forth to develop and market the same technology as spectral domain OCT. Although this technology is exciting and is taking “center stage”, other interesting imaging techniques are beginning to develop.

Autofluorescence utilization is becoming more and more common and the information that it yields may play an important role by improving our understanding of AMD and other hereditary retinal disorders. The technology that forms the foundation of autofluorescence has improved rapidly in the last few years and this imaging modality is about to enter “prime time” in the retina world.

Ultrawide angle imaging is another exciting technology that may have retina specialists rethinking some of their understanding and approaches to retinal vascular diseases (e.g, diabetic retinopathy, vascular occlusions, etc), uveitis, and heritable retinal diseases. It is a revolutionary system that can improve our understanding of many common retinal diseases. In this article, I hope to provide a brief overview to some of the technologies that may develop alongside spectral domain OCT.

Autofluorescence (AF)
Although fundus autofluorescence has received particular attention recently, it has actually been around for some time.. Autofluorescence was initially described prior to initiating the dye injection in fluorescein angiography. At that time, it was described as “pseudofluorescence” [1]. With the advent of the confocal scanning laser ophthalmascope (cSLO) [2,3], autofluorescence has become much more functional as a tool for evaluating the health of the RPE (among other things). Autofluorescence can also be performed with a standard fundus camera incorporating special filters [4]. Images obtained using this technique are of lower quality due to the presence of naturally occurring fluorophores in the lens and other structures of the eye. Also, because of the low levels of illumination created by autofluorescence, multiple images (usually 4-16) are obtained and are averaged with normalized pixel values represented in the final image.

Autofluorescence of the fundus is primarily due to the presence of lipofuscin (along with other fluorophores) in the RPE. Lipofuscin accumulates in aging RPE cells and represents the incomplete degradation of photoreceptor outer segments [5]. Increased autofluorescence can be seen with RPE dysfunction representing a decreased ability of the RPE to metabolize or eliminate the byproducts of phototransduction. Decreased autofluorescence occurs with the loss of photoreceptor outer segments. Hence autofluorescence can give information regarding the health of the RPE and outer retina in various disorders.

Autofluorescence adds insight into various disease states. Diseases characterized by the accumulation of fluorophores (Best disease and Stargardt’d disease) shows characteristically intense autofluorescence [6.7]. Autofluorescent findings may also help to explain the lack of visual recovery in some cases of central serous chorioretinopathy [8]. AMD demonstrates autofluorescent findings that can predict progression of geographic atrophy [9], as well as help characterize drusen and pigment epithelial detachments. Most interesting in “wet” AMD is the use of autofluorescent characteristics as a possible predictor of visual acuity improvement with the use of anti-VEGF therapy [10].

Currently, the only cSLO-based system available for obtaining autofluorescent images is the Heidelberg Retina Angiograph (the HRA classic, HRA 2, and Spectralis HRA; Heidelberg Engineering, Heidelberg, Germany). The Spectralis is a unique device that is essentially the “Swiss Army Knife” of retinal imaging. This device has the ability to perform 6 different imaging modalities including: fluorescein angiography, ICG, autofluorescence, high speed/resolution OCT, red-free, and infrared imaging. Not only can the Spectralis perform all of these different imaging modalities (some at the same time), but it creates a reference point for location and correction of these various images to ensure that the same points are being imaged from visit to visit. It should also be noted that cSLO instuments from both Rodenstock (Rodenstock, Weco, Dusseldorf, Germany) and Zeiss (Zeiss, Oberkochen, Germany) are in development.

Ultrawide Angle Imaging
Fluorescein angiography has been fundamental to the understanding of vascular disorders affecting the retina and choroid. Since it was first described in 1961 [11], arguably, no diagnostic procedure has led to a better understanding of diseases that affect the posterior pole than angiography. From A-to-Z (or AMD to AZOOR), fluorescein angiography was essential in our understanding of the most common and the rarest of retinal disorders. Since its inception, fluorescein angiography has undergone incremental improvements in camera systems, image processing, and the transition to digital angiography. The gradual evolution in angiography has led to higher quality images in a more patient-friendly (quicker) method.

The next step in this evolution is that of ultrawide angle angiography. The Optos P200A (Optos Inc., Dunfermline, Scotland) is the first noncontact system that offers up to a 200 degree view of the retina in a single image. I have had the opportunity to utilize this system over the last 6 months and must admit that it has changed my approach to many retinal diseases. In no disease was imaging of the retinal periphery more valuable than diabetic retinopathy.

Initially, I began obtaining ultrawide angle angiography in patients with proliferative diabetic retinopathy. My intent was to identify the area of neovascularization (NVE) and degree of nonperfusion in patients presenting with mild vitreous hemorrhage. While imaging these (affected) eyes, I was astounded to see that, often, the fellow (asymptomatic) eye had more profound changes than the eye with hemorrhage. This is particularly important in diabetic patients due to the fact that a hemorrhage in their fellow eye would leave them unable to drive, dose their insulin, and perform other vital activities of daily living. These findings led me to perform earlier panretinal laser in the fellow eye in an effort to “head-off” any problems that may develop.

Patients with clinically significant diabetic macular edema also demonstrated a wide variety of peripheral findings on ultrawide angle angiography. These findings ranged from excellent peripheral perfusion to extreme nonperfusion. The cases with extensive nonperfusion seemed (in my clinical observation) to respond more favorably to intravitreal Avastin (bevacizumab). This association has been described by others (primarily Steve Schwartz, MD and his colleagues at UCLA) with access to the Optos system.

This is an exciting time to practice retina. Improvements such as anti-VEGF therapy and small gauge surgery have made retina a great area to specialize in. These new technologies in retinal imaging will continue to add to this excitement and will help our understanding of various retinal conditions. This understanding will lead to better treatments and outcomes.

References
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2. von Ruckmann, A., F.W. Fitzke, and A.C. Bird. Distribution of fundus autofluorescence with a scanning laser ophthalmoscope. Br J Ophthalmol. 1995: 79(5); 407-412.
3. Delori, F.C., et al. In vivo fluorescence of the ocular fundus exhibits retinal pigment epithelium lipofuscin characteristics. Invest Ophthalmol Vis Sci. 1995. 36(3): 718-729.
4. Spaide, R.F. Fundus autofluorescence and age-related macular degeneration. Ophthalmology. 2003. 110(2): 392-399.
5. Feeney-Burns, L., E.R. Berman, and H. Rothman. Lipofuscin of human retinal pigment epithelium. Am J Ophthalmol. 1980. 90(6): 783-791.
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9. Schmitz-Valckenberg, S., et al. Correlation between the area of increased autofluorescence surrounding geographic atrophy and disease progression in patients with AMD. Invest Ophthalmol Vis Sci, 2006. 47(6): 2648-2654.
10. Heimes, B., et al., Foveal RPE autofluorescence as a prognostic factor for anti-VEGF therapy in exudative AMD. Graefes Arch Clin Exp Ophthalmol. 2008. 246(9): 1229-1234.
11. Novotny, H.R. and D.L. Alvis, A method of photographing fluorescence in circulating blood in the human retina. Circulation. 1961. 24: 82-86.