Don’t wake the sleeping dragon
Catching exudative conversion can be the difference-maker in maintaining your patients’ vision—making knowing the risk factors crucial. “Research suggests that exudative conversion is 15 times more likely to happen in eyes with choroidal neovascularization (CNV) than those without,” notes Dr. Majcher.1-3 So how should you manage non-exudative age-related macular degeneration (AMD) patients with CNV?
Dr. Majcher faced this very question when a 68-year-old male patient with a dry AMD history presented to her clinic. In both the clinical exam and color fundus photography, his left eye showed more notable macular degeneration features. However, neither eye had hemorrhaging, exudate, or obvious subretinal fluid. Further assessment, using ocular coherence tomography (OCT), uncovered a shallow, irregular pigment epithelial detachment (PED), a red flag for potential sub-retinal pigment epithelium (RPE), non-exudative CNV—which further visualization, using OCT-angiography (OCTA), could confirm.
“There are many presets available for assessing OCTA,” Dr. Majcher explains. “Because outer retinal disease was my focus here, I used the outer retinal-to-choriocapillaris (ORCC) slab, an incredibly valuable tool for detecting subretinal or choroidal neovascularization.” Using this preset, Dr. Majcher observed a well-defined neovascular complex within the PED—alongside red coloration on the B-scan—solidifying her evaluation of non-exudative neovascular AMD.
“Whether you refer straightaway, even before there’s fluid or hemorrhage, or monitor patients in-house is really a matter of personal comfort,” Dr. Majcher says, opting to monitor this patient in-house every three months. However, he didn’t attend his first follow-up—and six months post-initial presentation, there’d been substantial changes. Retina Workspace lets us compare baseline and follow-up raster scans,” highlights Dr. Majcher. “At six months there was new overlying subretinal and intraretinal fluid; similar functionality for synchronizing macular cube OCT scans made the intraretinal fluid and exudate presence clear.”
OCTA comparisons demonstrated choroidal neovascular membrane lesion morphological changes. It had grown in size and developed lacy, looping capillaries on its margin. These signs all pointed towards active neovascularization—and, unfortunately, the dragon’s awakening.
Looks wet, acts dry
Does the presence of hyporeflective spaces mean exudation? Dr. Schneider points to the case of a 71-year-old male patient—referred because of suspicious drusen—to argue that it is not necessarily the case. Color fundus photography showed pigment clumping and extensive drusen in the central macula (OU), alongside a large drusenoid PED(OD), but despite this, there were no signs of exudation. Dr. Schneider used structural OCT to look closer at the drusenoid PED and observed hyporeflective spaces at the base—a potential sign of subretinal fluid.
These findings prompted Dr. Schneider to order fluorescein angiography (FA), which showed staining of drusen in the early and mid phases, followed by more prominent drusenoid PED staining. However, there was no clear leakage—or CNV—in either eye. “Given that it can be challenging to interpret traditional angiography when there’s lots of staining from drusen or vitelliform material, I typically also use OCTA,” Dr. Schneider explains. “I couldn’t see any obvious CNV, En Face on the ORCC slab. Additionally, the corresponding cross-sectional image displayed no significant flow anomalies—another sign there wasn’t CNV.”
Despite this, Dr. Schneider remained suspicious and monitored the patient carefully. But at both the three- and eight-month follow-ups, there were still no CNV indicators, providing enough evidence to space future appointments out. Three years post-initial presentation, and following the collapse of the drusenoid PED—which had been continually growing from eight months onwards—Dr. Schneider observed little occurring in the RPE, further increasing his confidence that there wasn’t CNV.
“It’s a reminder that not all hyporeflective spaces represent exudative fluid,” he says. “Draping or tenting artifacts can be common causes in AMD. However, there are other potential confounding conditions we may commonly encounter in-clinic, including vitelliform lesions, cystic degenerative changes, outer retinal tubulations, and cavitations as part of macular telangiectasia type 2 (MacTel2).” Dr. Schneider does note that the negative predictive value of OCTA isn’t perfect; although cases like this demonstrate a reduced likelihood of CNV, he still follows these patients closely.
Seeing beyond the clinical exam
“OCTA provides us with a detailed, fine, and high-resolution look at the microvasculature, letting us detect lesions not always visible on clinical examination,” says Dr. Majcher. One case that demonstrates this is that of a 52-year-old male with poorly controlled type 2 diabetes. Dr. Majcher’s initial assessment was that he had severe/very severe non-proliferative diabetic retinopathy (NPDR), due to the presence of prominent intraretinal hemorrhaging, venous beading, and numerous cotton-wool spots—alongside a lack of noticeable neovascularization, preretinal vitreous hemorrhage, or traction.
But then she considered the AngioPlex OCTA montage. “A montage provides us with a 14x14 mm total image composed of five scans that are then automatically knitted together,” she explains. “It’s so useful for visualizing areas of both retinal nonperfusion and preretinal neovascularization that could signify early PDR.” The inner retinal circulation of the superficial preset highlighted areas of nonperfusion, and, alongside this, the vitreoretinal interface—used to detect early preretinal neovascularization due to the inherent avascular nature of healthy vitreous—revealed a small area of neovascularization elsewhere (NVE). Dr. Majcher also confirmed the vascularized nature of this tissue by evaluating the corresponding cross-sectional B-scan overlay.
“Ultimately, this patient was diagnosed as having low-risk PDR, and referred for panretinal photocoagulation,” recalls Dr. Majcher. “An area of NVE on color fundus photography can be incredibly subtle—and if round, easy to mistake as a large dot and blot hemorrhage. This diagnosis was assisted by OCTA; if I’d just stopped with the clinical examination, I would have missed it.”
Ex-cysting without edema
When a 59-year-old patient was referred to Dr. Schneider for cystoid macular edema (CME), he observed both the presence of cystoid spaces in the central macula of both eyes, alongside a slight loss of retinal transparency in the parafoveal region—which also had anomalous vasculature. Although structural OCT showed inner-retinal hyporeflective spaces, the retinal thickness was, notably, relatively normal. Additionally, aside from a small area of inner segment/outer segment disruption nasally, OD, the outer retina was relatively intact. Mid-to-late FA showed prominent temporal parafoveal staining, OU—with a little staining, superior nasally, OS. However, there wasn’t any evidence of other microvascular abnormalities (such as microaneurysms or anastomotic vessels) or of CNV. So where was this CME coming from?
To answer this, Dr. Schneider turned to OCTA. A high-definition scan of the superficial capillary plexus taken by the CIRRUS 6000 showcased several important features. Both eyes had dilated feeding arterioles branching into the foveal avascular zone (FAZ), alongside multiple draining venules. Additionally, significant rarefaction of the parafoveal capillaries—which had increased within the intravascular spaces—resulted in an incredibly anomalous FAZ shape and size, OD, and rendered it almost completely missing, OS.
More obvious changes were found when Dr. Schneider considered the next slab down: the deep capillary plexus. Here, he observed telangiectatic vascular changes, indicative of type-2 macular telangiectasia (MacTel2), not CME. “It’s really striking because although you can see leakage and staining with traditional FA, even in its mid and early phases, you can’t see the level of microvascular detail needed to determine the diagnosis, making OCTA so critical here,” notes Dr. Schneider. “OCTA also provides equal quality of the vascular architecture between the two eyes—as opposed to FA, where there’s one transit eye. Additionally, FA staining can obscure changes to the parafoveal capillaries and secondary subretinal neovascularization—if it occurs, which is what we’re looking to visualize. We don’t have that problem with OCTA.”
