SD-OCT and OCTA in the Evaluation of Diabetic Retinopathy

Educational Objectives

The goals of this program are to improve the diagnosis of diabetic retinopathy and the diagnosis and treatment of idiopathic central serous choroidopathy (CSR). After hearing and assimilating this program, the clinician will be better able to:

1. Use optical coherence tomography angiography (OCTA) to monitor for pathological changes in the retinal layers in patients with diabetes mellitus.

2. Choose parameters measurable on OCTA images with high sensitivity and specificity for detecting early physiological changes in the retinal capillary plexuses of patients with diabetes mellitus.

Summary

Background: depth-resolved technology of optical coherence tomography angiography (OCTA) details superficial, middle, and outer retina as well as ischemia of small retinal capillary levels; in contrast, fluorescein angiography (FA) shows ischemia 2-dimensionally (ie, ischemia appears to affect only superficial surface of retina); ischemic patch seen on FA in patients with diabetes mellitus (DM) associated with ischemic changes at every level on OCTA, including outer retina, which contains photoreceptors (PRs)

Study on outer retina: prior to OCTA, OCT used to observe outer retinal changes; changes in PRs easily visible in foveal avascular zone (FAZ) because it has only one capillary layer; results — enlarged FAZ reveals thinning of outer nuclear layer (ONL) and PRs, which differs from findings associated with inner retinal ischemia and reveals complexity of ischemia secondary to DM

Oxygen gradient: choroid has oxygen saturation of almost 100%; as oxygen traverses outer retina, it enters highly ischemic “watershed zone” in ONL; inner segments have highest consumption of oxygen because of high concentration of mitochondria; therefore, PRs vulnerable to ischemia if deep capillaries damaged; 3 blood vessel layers located in areas with highest mitochondrial and oxygen demand (ie, inner and outer plexiform layers, ganglion cell layers, and choroid)

PR study: using OCTA images, speaker attempted to correlate PR damage with loss in deep capillaries; results — effects on superficial capillary areas do not consistently correlate with effects on deep capillary areas; found that PRs may be damaged in areas of deep capillary destruction

Adaptive optics study: included patients with enlarged FAZ and no history of laser treatment; one patient had ring of apparent PR loss on OCT; areas showing no outer segments on OCT corresponded with areas showing no outer segments on adaptive optics; therefore, ring represented true loss of PRs rather than artifact

Photoreceptor heterogeneity packing index: in healthy eye, each PR adjacent to 6 or 7 others; deviations from normal pattern (ie, increase in heterogeneity) may indicate decrease in PR density; study examined patients with DR with and without ischemia; results — study found linear relationship between increases in heterogeneity and increases in deep capillary ischemia; deep capillary ischemia can affect PRs; therefore, patients with DM may have PR loss

Early OCTA technology: machine algorithms split retina into only 2 layers (inner and outer); including middle capillary layer within inner or outer retina may affect measurements

Projection artifact: highly reflective layer reflects all layers above it; speaker used reverse projection artifact algorithm to isolate 3 capillary layers; anatomy and distribution of layers differ significantly among layers; middle capillary plexus has smallest FAZ

OCTA images in DR: OCTA shows variable waves of ischemia at different levels, with no overlap; when mapped together, areas seen with 1, >1, or no capillary layer; this differs from normal eyes, in which every patch of retina covered

Capillary density study: speaker’s hypothesis — neurons with different functions affected differentially by DR; observing neurons individually should allow visualization of early changes associated with DR

Methods: study compared changes in retina on OCTA among groups of patients with healthy eyes, with DM but no DR, with NPDR, and with PDR; multiple parameters analyzed, including FAZ, parafoveal vessel density, percent area of nonperfusion and adjusted flow index (AFI)

Results: using metric of capillary density, researchers found no change in transition from healthy patient to patient with DM but no DR; significant drop in capillary density found in NPDR and PDR; capillary nonperfusion increases at all levels as disease advances

Clinical significance: in patients with early DM without DR, significant increase in AFI observed in superficial capillary plexus (relative to healthy patients), but minimal or no change occurs in AFI of middle and deep plexus; as DR progresses, deep retina changes dramatically while superficial retina changes minimally; speaker hypothesizes that increased flow at superficial retina shunts flow away from deep retina, which exacerbates ischemia and may lead to PR loss

Summary: changes differ among different retinal levels with increasing DR; if layers divided into 2 sets, middle and deep layers should be grouped together, with superficial layer in second set; flow in superficial layer increases early in DR, but observations on this level uninformative after further progression has occurred

Measuring flow with adaptive optics: results show that blood flow increases in patients with early DM (prior to development of DR), then steeply decreases in late disease

Predicting DR: speaker’s group assessed all parameters measurable on OCTA (plus hemoglobin A1c and duration of DM) in attempt to determine whether one parameter or combination of parameters highly sensitive and specific for predicting risk for DR; on univariate analysis, 7 parameters identified as significant; no individual parameter found to be highly specific; however, combining 3 parameters mproved sensitivity, specificity, and area under curve (in men and women); in predicting risk for PDR in patients with NPDR (ie, high-risk patients), area under curve 84%; model had better sensitivity and specificity for differentiating patients with no DR from patients with any DR (suggesting role for this model in screening); model for identifying high-risk patients will require further research

Readings

Ashraf M et al: Statistical model of optical coherence tomography angiography parameters that correlate with severity of diabetic retinopathy. Invest Ophthalmol Vis Sci 2018;59(10):4292-4298; Fayed AE, Fawzi AA: Projection resolved optical coherence tomography angiography to distinguish flow signal in retinal angiomatous proliferation from flow artifact. PloS One 2019;14(5):e0217109; M Nesper PL et al: Quantifying microvascular abnormalities with increasing severity of diabetic retinopathy using optical coherence tomography angiography. Invest Ophthalmol Vis Sci 2017;58(6):BIO307–BIO315. doi:10.1167/iovs.17-21787; Onishi AC et al: Importance of considering the middle capillary plexus on OCT Angiography in diabetic retinopathy. Invest Ophthalmol Vis Sci 2018;59(5):2167-2176; Onishi AC et al: Multilevel ischemia in disorganization of the retinal inner layers on projection-resolved optical coherence tomography angiography. Retina Phila Pa April 2018; Onishi AC, Fawzi AA: An overview of optical coherence tomography angiography and the posterior pole. Ther Adv Ophthalmol 2019;11:2515841419840249; Park JJ et al: Visualizing structure and vascular interactions: macular nonperfusion in three capillary plexuses. Ophthalmic Surg Lasers Imaging Retina 2018;49(11):e182-e190; Rosen RB et al: Earliest evidence of preclinical diabetic retinopathy revealed using OCT angiography (OCTA) perfused capillary density. Am J Ophthalmol January 2019; Scarinci F et al: Deep retinal capillary nonperfusion is associated with photoreceptor disruption in diabetic macular ischemia. Am J Ophthalmol 2016;168:129-138.

Disclosures

For this program, members of the faculty and planning committee reported nothing relevant to disclose.

Acknowledgements

Dr. Fawzi was recorded at the 12th Annual Retina Symposium, held April 5, 2019, in Chicago, IL, and presented by the Illinois Eye and Ear Infirmary at the University of Illinois, Chicago. For information on future CME activities from the Illinois Eye and Ear Infirmary, please visit chicago.medicine.uic.edu. The Audio Digest Foundation thanks the speakers and the Illinois Eye and Ear Infirmary for their cooperation in the production of this program.

CME/CE INFO

Accreditation:

The Audio- Digest Foundation is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians.

The Audio- Digest Foundation designates this enduring material for a maximum of 0 AMA PRA Category 1 Credits™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

Audio Digest Foundation is accredited as a provider of continuing nursing education by the American Nurses Credentialing Center's (ANCC's) Commission on Accreditation. Audio Digest Foundation designates this activity for 0 CE contact hours.

Lecture ID:

OP571502

Expiration:

This CME course qualifies for AMA PRA Category 1 Credits™ for 3 years from the date of publication.

Instructions:

To earn CME/CE credit for this course, you must complete all the following components in the order recommended: (1) Review introductory course content, including Educational Objectives and Faculty/Planner Disclosures; (2) Listen to the audio program and review accompanying learning materials; (3) Complete posttest (only after completing Step 2) and earn a passing score of at least 80%. Taking the course Pretest and completing the Evaluation Survey are strongly recommended (but not mandatory) components of completing this CME/CE course.

Estimated time to complete this CME/CE course:

Approximately 2x the length of the recorded lecture to account for time spent studying accompanying learning materials and completing tests.