Ophthalmic Medical Education Summit: Imaging for the Inner and Outer Retina

Working within an academic practice, clinical practicality is a key focus for Dr. Steen. A case demonstrating this is of a 72-year-old patient who was already being medically managed for bilateral primary open-angle glaucoma (POAG) and hypercholesterolemia, and came to the clinic after being unhappy with her vision. Observing changes to the retinal pigment epithelium (RPE), Dr. Steen conducted near-infrared reflectance (NIR) imaging.

“This is something I like to utilize, especially in age-related macular degeneration (AMD),” she says. “It allows us to observe a greater amount of drusen than color fundus photography alone.” Using OCT-A to look closer at the areas highlighted by NIR imaging, Dr. Steen observed fine drusen, consistent with the appearance of reticular pseudodrusen or subretinal drusenoid deposits. “This is an important biomarker that indicates an elevated risk of progression to late-stage disease,” explains Dr. Steen; however, identifying biomarker abnormalities is only the first stage of understanding a patient’s condition. “Following diagnosis, just like in glaucoma, we need to determine whether patients are progressing, and if so, how quickly.”

Comparing the patient’s fundus photography and isolated OCT-A scans between 2019 and 2024, it was clear there had been an increase in drusen load and a decrease in choroidal thickness in both eyes. “This is a POAG patient, so we needed to determine the impact of her macular degeneration on the overall evaluation of potential glaucomatous optic neuropathic progression,” Dr. Steen explains. In this case, structural and functional imaging highlighted a decrease in the patient’s ganglion cell layer inner plexiform layer (GCL-IPL) thickness; however, this was not in a characteristic glaucomatous pattern, and, alongside this, there was no significant change in the retinal nerve fiber layer (RNFL). “Looking at the totality of the data, it seems that this GCL-IPL progression is solely related to this patient's macular degeneration, meaning that her target pressure seemed to be reasonable for her POAG disease state,” says Dr. Steen. “It's important to keep in mind a patient's macular pathology and its potential impact on their other ocular issues.”

Beyond simply identifying progression, quantifying progression-associated changes objectively over time is also incredibly useful when evaluating patients. Dr. Steen shares a second case of an 84-year-old female with a history of rhegmatogenous retinal detachment and a known history of non-exudative AMD, in whom OCT-A analysis highlighted choroidal hypertransmissibility, potentially activated microglia—another important risk factor for progression to late-stage disease—and drusenoid pigment epithelial detachment. Quantifying these changes objectively over time required Dr. Steen to turn to the RPE elevation map in the ZEISS Retina workspace. She observed that the drusen volume increased from near-zero over time to over 0.07 mm3 in 2023, but appeared to stabilize—if not drop slightly—by 2024. “My biggest question was whether she was at her maximum drusen volume and at the tipping point where she’d begin to move towards atrophy.”

This patient’s presentation led Dr. Steen to use OCT-A to confirm that choroidal neovascularization wasn’t present then. “OCT-A is really valuable in evaluating for non-exudative choroidal neovascularization or choroidal neovascular membranes that haven’t yet broken through the Bruch's membrane RPE complex,” she says. “These two cases highlight different risk factors for progression to late-stage disease; however, it’s not just about identifying those risk factors, but utilizing objective measurements in evaluating our patients for change over time.”

Multimodal imaging has substantial utility within Dr. Majcher’s diabetes retinopathy (DR) prognostic workflow. When an asymptomatic 41-year-old type-2 diabetes patient presented for his routine diabetes examination, although there was no gross evidence of proliferation in the ultrawide color fundus photography taken using the ZEISS CLARUS camera, the presence of severe intraretinal hemorrhaging, especially in the periphery, prompted further investigation. “Eyes with predominantly peripheral diabetic retinopathy, where the majority of the lesions are outside the standard seven-field Early Treatment Diabetic Retinopathy Study area, are at greater risk of progression over time, regardless of the imaging modality,” Dr. Majcher explains.¹ She also observed peripheral vascular sheathing, suggesting widespread peripheral ischemia and retinal nonperfusion. Further investigation with OCT-A highlighted intraretinal microvascular abnormalities (IRMAs) and several cotton wool spots. “These are further telltale signs of substantial retinal nonperfusion—and the greater the degree of retinal nonperfusion, the greater the risk of progression.”

But how far exactly had this patient progressed? Dr. Majcher noted a vascular lesion that, based on its size and morphologic apparent sea-fan pattern, was suspicious for neovascularization elsewhere (NVE), and thus proliferative DR (PDR). Using the slice navigator, she was able to examine this area of suspicious vasculature further to clarify that the lesion was intraretinal, and confirm the patient as having non-proliferative DR.

Although non-proliferative, the patient’s condition was severe, displaying multiple high-risk biomarkers associated with inferior visual prognosis in his macular cube OCT-A scans. “It's important to recognize imaging features associated with high risk of progression to PDR (predominantly peripheral lesions and extensive OCT-A retinal nonperfusion), alongside the structural OCT-A and OCT-A features suggestive of worse visual prognosis, and those corresponding to OCT-A nonperfusion—including inner retinal atrophy, inner retinal layer disruption, retinal ischemic perivascular lesions (RIPLs), photoreceptor ellipsoid zone loss, and OCT-A evident macular ischemia.”

“One clinical dilemma I've run into over the years is differentiating chronic retinal vein occlusion (RVO) from chronic retinal artery occlusion (RAO),” acknowledges Dr. Modi. While it's easier to distinguish between retinal vein occlusion (RVO) and retinal artery occlusion (RAO) in their acute stages—where a quadrant of retinal hemorrhages typically suggests a branched RVO (BRVO), and the whitening of the retina with a cherry red spot indicates an RAO—the differences become less clear as these conditions progress into their chronic phases. Differing causes, management, and implications between RAOs and RVOs make this distinction crucial, and using OCT-A, Dr. Modi has found a way to reliably do so. But how? “When you look at chronic, and especially ischemic, BRVO using OCT-A, the hallmark identifying feature is venous-to-venous anastomosis and vascular remodeling, specifically crossing the raphe,” he explains.

“RAOs, for whatever reason, have no vascular reanastomosis—instead, all we see is density loss of the capillaries at the superficial capillary plexus (SCP), and at the deep capillary plexus (DCP).”

Using OCT-A and being aware of these identifiers has aided Dr. Modi when assessing previously undiagnosed patients. In one such patient, a 66-year-old female, although the fundus photography and OCT-A horizontal foveal slice images taken at her first evaluation highlighted several hallmarks associated with DR, Dr. Modi also observed uniform thinning of the inferior retina—something not consistent with DR alone. “Using OCT-A, we saw clear signs of SCP and DCP loss,” he explains. “Alongside a PDR event, this patient had a chronic BRAO that had previously been undiagnosed.” Having identified this, and knowing the increased risk of developing heart attacks and strokes that severe DR patients have,^2,3 Dr. Modi was then able to evaluate the ROA as a stroke, conduct an intensive medical investigation, and obtain stroke parameter control labs.

And, with the new OCT-A current procedural terminology code coming into effect at the start of this year, the increased utility this imaging provides will likely continue to expand. “Currently, not everybody has OCT-A,” he says. “The billing code for OCT-A may ultimately change how we implement this imaging modality, and may provide further meaning to the ways that we use this in clinical practice.”