The extent to which optical coherence tomography (OCT) has transformed how retina specialists diagnose and manage diabetic eye disease is impressive. This workhorse technology is now the gold standard for diagnosing diabetic macular edema (DME), monitoring treatment response, and determining when to re-treat. As a clinical tool, OCT is evidence-based. Its use is driven and supported by large clinical studies, many conducted by the Diabetic Retinopathy Clinical Research Network (drcr.net ).

In the era of anti-VEGF therapy, we no longer decide whether to treat patients based on “clinically significant macular edema (CSME)” as seen on clinical exam, ophthalmoscopy, and fundus photographs. Instead, the CSME criterion has been replaced by whether increased retinal thickness as measured by OCT is center-involving. Once we make the decision to treat, we use OCT to monitor the response. Following drcr.net and other trial protocols, our focus is normalizing central retinal thickness on OCT to the greatest extent possible. When that is achieved, we continue to use OCT to watch for recurrence and determine the best interval between treatments.

UTILITY BEYOND RETINAL THICKNESS

OCT potentially has a role in DME management beyond assessment of retinal thickness. It identifies other retinal abnormalities that may be helpful for informing our expectations of treatment outcomes and patient prognosis. A number of potential biomarkers can be assessed.

Disorganization of the retinal inner layers (DRIL), for example, seems to be a sign that ischemia is likely present and visual outcomes may not be as good (Figure 1A).¹ OCT also shows the integrity of the outer retinal bands, i.e., the ellipsoid zone and external limiting membrane. Solid data that have been published indicate that eyes with disrupted outer retinal bands may have inferior vision recovery after treatment.²

Hyper-reflective spots are another OCT-visualized biomarker being evaluated for prognostic value.³ Commonly, these spots or dots are evidence of lipid exudates. When we see a significant number of such exudates, especially if they’re tracking toward the foveal center, we increasingly interpret it as a negative prognostic sign. Furthermore, hyper-reflective spots are a reminder to make sure the patient is working with his or her internist on lipid level control. It has also been theorized that even very small hyper-reflective spots may be significant, possibly indicating activated microglia or migrating RPE cells, and/or markers of inflammation.

Larger prospective trials will determine just how closely DRIL, disruption of the outer retinal bands, and hyper-reflective spots are associated with poorer visual outcomes and less-than-desired response to anti-VEGF therapy and how we should use the findings in day-to-day practice.

Other OCT biomarkers, such as diffuse vs. focal/cystoid DME and the presence of subretinal fluid, were previously thought to be relevant to how an eye would respond to therapy. However, they haven’t proved to be important in terms of anti-VEGF therapy or how patients should be managed.

OCTA: A NEW FRONTIER

OCT angiography (OCTA) is one of the newest diagnostic technologies available to retina specialists, and it will likely prove to be of value in the realm of DME. For example, OCTA can detect lesions relevant to DME, such as microaneurysms.

That said, it’s important to note that we can’t rely on OCTA alone in cases where part of the plan is to treat with focal laser. First, not all microaneurysms are visible, only a subset. There’s indication that the more hypo-reflective microaneurysms visible on structural OCT are less likely to be detected on OCTA.⁴ Second, OCTA doesn’t discern which microaneurysms are leaking. Therefore, it doesn’t indicate which ones to treat.

OCTA can be a potent and useful tool for evaluating macular ischemia, which is quite relevant given what we know about DRIL, which leads us to suspect it. OCTA has shown us that ischemia may involve different retinal layers (Figure 1B-C). Following its extent may be useful from a prognostic standpoint.

Finally, OCTA appears to be much more sensitive than fluorescein angiography for assessing macular perfusion. This is likely to be very helpful as we collectively continue to monitor what impact anti-VEGF therapy may or may not have on macular perfusion.

REFERENCES

1. Sun JK, Lin MM, Lammer J., et al. Disorganization of the retinal inner layers as a predictor of visual acuity in eyes with center-involved diabetic macular edema. JAMA Ophthalmol. 2014;132(11):1309-1316.
2. Santos AR, Costa MA, Schwartz C, et al. Optical coherence tomography baseline predictors for initial best-corrected visual acuity response to intravitreal anti-vascular endothelial growth factor treatment in eyes with diabetic macular edema: the CHARTRES study. Retina. 2018;38(6):1110-1119.
3. Hwang HS, Chae JB, Kim JY, Kim DY. Association between hyper-reflective dots on spectral-domain optical coherence tomography in macular edema and response to treatment. Invest Ophthalmol Vis Sci. 2017;58(13):5958-5967.
4. Parravano M, De Geronimo D, Scarinci F, et al. Diabetic microaneurysms internal reflectivity on spectral-domain optical coherence tomography and optical coherence tomography angiography detection. Am J Ophthalmol. 2017;179:90-96.

Dr. Sadda is president and chief scientific officer for the Doheny Eye Institute and professor of ophthalmology at the University of California - Los Angeles.