Case 1

A 68-year-old woman with a history of dry age-related macular degeneration (ARMD) and geographic atrophy OU presented to the office complaining of some distortion in her left eye ( ▶ Fig. 19.1). The visual acuity was 20/50 OD and 20/40 OS. On examination, there was a patch of geographic atrophy (GA) involving the nasal and superior macula ( ▶ Fig. 19.1a). There was a dot hemorrhage located just superotemporal to the fovea just inferior to the edge of clinically evident GA. Early-phase fluorescein angiography (FA) revealed a window defect in the area of GA ( ▶ Fig. 19.1b). Late-phase FA revealed a small area of hyperfluorescence in the direct area of the retinal hemorrhage seen clinically consistent with a neovascular membrane or retinal angiomatous proliferation (RAP) lesion ( ▶ Fig. 19.1c). Optical coherence tomography (OCT) angiogram of superficial retina plexus reveals a focal area of increased signal corresponding to the area of retinal hemorrhage consistent with type 3 choroidal neovascular membrane (CNVM) or RAP lesion ( ▶ Fig. 19.1d). OCT angiogram of deep retinal plexus reveals the same area of increased signal corresponding to the area of retinal hemorrhage consistent with type 3 CNVM or RAP lesion ( ▶ Fig. 19.1e). OCT angiogram of outer retina revealed a focal decorrelation signal corresponding to the area of retinal hemorrhage consistent with type 3 CNVM or RAP lesion extending into outer retina ( ▶ Fig. 19.1f). The structural OCT shows the presence of intraretinal fluid (inset). OCT angiogram of choroid choriocapillaris shows projection artifact of superficial retinal plexus onto choroidal image ( ▶ Fig. 19.1g).

The initial assessment of the patients imaging allowed us to confirm the presence of wet ARMD OS. The OCT angiogram provided information we would not have had from the FA alone by allowing us to determine the neovascular membrane originated in the retina itself consistent with a type 3 CNVM or RAP lesion. The OCT angiogram in this patient also highlights the difficulties related to projection artifacts confusing the images obtained in other slabs. Based on the images obtained, a decision was made to proceed with anti–vascular endothelial growth factor (anti-VEGF) therapy OS.

Day 1 post-injection of intravitreal Lucentis (IVL) OS, OCT angiogram of the superficial and deep retinal plexus shows the RAP lesion has disappeared ( ▶ Fig. 19.1h, i). OCT angiogram of the outer retina shows disappearance of the RAP lesion and the inset structural OCT scan shows the intraretinal fluid has resolved as well ( ▶ Fig. 19.1j). OCT angiogram choroid choriocapillaris shows projection artifact of the superficial retina but no CNVM ( ▶ Fig. 19.1k). Two weeks post-IVL number 1 OS, the patient returned for another OCT angiogram and this scan continued to show no evidence of the RAP lesion and no fluid on the structural OCT ( ▶ Fig. 19.1l). One month post-injection, the patient returned for her second IVL OS ( ▶ Fig. 19.1m). The OCT angiogram at this visit did not show any evidence of recurrence of the RAP lesion or fluid on the structural OCT. One month post-injection number 2, the patient returned for her third IVL OS ( ▶ Fig. 19.1n). The OCT angiogram at this visit did not show any evidence of recurrence of the RAP lesion or fluid on the structural OCT.

The serial usage of OCT angiograms in this patient was able to elegantly show the positive response to the initial injection of intravitreal anti-VEGF therapy with regression of the RAP lesion within 24 hours. Given OCT angiograms are noninvasive, they can be performed frequently and may become very useful in gauging a patient’s response to therapy. During the patient’s monthly visits, there was no evidence of reperfusion of the RAP lesion at 1-month visits. This may be clinically valuable to determine at what interval a patient can get away without maintenance therapy.

19.2 Case 2

A 79-year-old woman presented with a history of mild dry ARMD OU ( ▶ Fig. 19.2). She had no visual complaints on presentation. Her visual acuity was OD 20/100 OS 20/80. The fundus examination revealed some stippled RPE pigmentary changes but no blood or obvious fluid OD ( ▶ Fig. 19.2a). The fundus examination OS revealed mild drusen and RPE changes ( ▶ Fig. 19.2b). The structural OCT OD revealed some subretinal fluid and intraretinal fluid ( ▶ Fig. 19.2c). The structural OCT OS revealed mild drusen ( ▶ Fig. 19.2d). The fluorescein angiogram early-phase OD showed a central RPE perfusion defect ( ▶ Fig. 19.2e). The mid-phase fluorescein angiogram OD showed stippled hyperfluorescence on the temporal border of the overt lesion ( ▶ Fig. 19.2f). The late-phase fluorescein angiogram OD showed progressive stippled hyperfluorescence now covering the entire lesion ( ▶ Fig. 19.2g). The OCT angiogram showed no overt changes in the superficial ( ▶ Fig. 19.2h) and deep ( ▶ Fig. 19.2i) retinal plexus, nor in the outer retina ( ▶ Fig. 19.2j), but did show an obvious large CNVM in the choriocapillaris ( ▶ Fig. 19.2k) characterized by a central feeder vessel with a branching fan-shaped pattern emanating from the feeder vessel.

Based on the patient’s initial multimodal imaging, a diagnosis of a type 1 occult CNVM from ARMD OD was made. Interestingly, the patient was asymptomatic at presentation, so a discussion was carried out about the nature of the pathology and risks of progression without treatment. The patient elected to commence anti-VEGF therapy with IVL.

One month post-IVL OD number 1, the structural OCT shows disappearance of the subretinal fluid and the OCT angiogram shows pruning of the peripheral new branches of the CNVM ( ▶ Fig. 19.2l). One month post-IVL OD number 2, the structural OCT is dry and the OCT angiogram shows an obvious drop in the perfusion of the CNVM complex ( ▶ Fig. 19.2m). One month post-IVL number 3 and number 4, the structural OCT stays dry and the OCT angiogram shows a similar reduction in the perfusion of the CNVM complex to the previous months ( ▶ Fig. 19.2n, o). One month post-IVL number 5, the structural OCT stays dry and there is obvious remodeling of the CNVM complex on the OCT angiogram ( ▶ Fig. 19.2p).

The sequential OCT angiograms used on this patient with wet ARMD provide another piece of information to guide us in our decision-making. The current management of patients with wet ARMD is largely based on the presence or absence of fluid on structural OCT scans. OCT angiograms now allow us to monitor the perfusion of the CNVM complex in response to therapy. Other investigators have already noted different patterns of therapeutic response to treatment with anti-VEGF therapies. Some CNVM complexes entirely disappear on OCT angiograms following therapy only to reappear as therapy wears off, providing valuable insight into the recurrence patterns for a given patient. Unfortunately, in our experience, although we have noted some patients who do show dramatic responses to anti-VEGF therapy with disappearance of the CNVM complex, the majority of patients tend to show a partial response like this patient with pruning of the branches of the CNVM complex and persistent flow in the trunk or feeder vessel. Many investigators have noted this similar phenomenon. The value of monitoring the perfusion of the CNVM complex and using this to guide treatment decisions has yet to be validated in clinical trials. We will need to better study and understand the patterns of response in CNVM complexes to determine if there are certain characteristics of the complex or their response to therapy, which can be used to guide therapy or provide prognostic information.

19.3 Case 3

A 68-year-old woman who has been getting intravitreal injections in her left eye for 8 months presented to the clinic ( ▶ Fig. 19.3). Her visual acuity was 20/200. She was put on a treat-and-extend regimen after her initial loading dose with a recurrence of fluid on structural OCT at 6-week intervals. Eight months into her treatment, OCT angiography became available with sequential images then taken at each follow-up visit to help in the decision of the timing of her next treatment. The fundus photo at the time of her 8-month visit with an obvious choroidal neovascular membrane is seen on exam with no obvious hemorrhage ( ▶ Fig. 19.3a). The structural OCT insert shows intraretinal fluid and a sub-RPE lesion at 6 weeks post-injection. As a result of the fluid on her structural OCT, she was asked to return at 4 weeks for her next injection. The OCT angiogram at this visit shows the CNVM complex in the choriocapillaris with an obvious sea fan configuration and a dry structural OCT ( ▶ Fig. 19.3b). Since the structural OCT was dry, she was extended to 5 weeks. OCT angiography at this visit showed what appeared to be increased perfusion of the CNVM complex with the same surface area and a dry structural OCT ( ▶ Fig. 19.3c). The interesting question arising from these images is, do we as clinicians stick to our trial-tested indications for treatment (structural OCT fluid) or do we take into account the new OCT angiogram image showing what appears to be increasing perfusion of the CNVM complex at a 5-week interval. A decision was made to have the patient return again at 4 weeks instead of 5 due to the concerns related to the presumed increasing perfusion of the CNVM complex at a 5-week interval. This decision was based on a presumption that increasing perfusion of the CNVM complex would likely precede the development of fluid in the retina and that comparing sequential images of the perfusion of the CNVM complex might allow clinicians to institute therapy at an earlier stage before fluid develops in the retina. This presumption, of course, is not validated in any clinical trials at this point and may be entirely wrong or only applicable in certain situations the characteristics of which have yet to be determined. Four weeks later, the patient returned for her next injection with an OCT angiogram showing what appears to be a marked reduction in perfusion with some obvious pruning of the sea fan vessels ( ▶ Fig. 19.3d). The structural OCT was dry. Based on the images, a decision was made to extend her next visit to 5 weeks. Five weeks later, the OCT angiogram showed what appeared to be a further reduction in perfusion with further pruning of vessels in the sea fan and a dry structural OCT again ( ▶ Fig. 19.3e). Based on these images, a decision was made to try and extend the interval to 6 weeks. Six weeks later, the OCT angiogram showed what appeared to be a significant reduction in perfusion of the CNVM complex with a dry structural OCT ( ▶ Fig. 19.3f). Given some skepticism about the dramatic improvement of the CNVM complex, the images were reviewed again; however, this time with manual segmentation. After manually segmented, the perfusion and surface area of the CNVM complex looked similar to that done 6 weeks previously ( ▶ Fig. 19.3g). The lesson learned from these images is extremely important for clinicians to realize particularly if you are going to try and sequentially compare the perfusion and surface area of CNVM complexes. Do not forget that each image obtained on a patient has autosegmentation software applied to it and that from visit to visit the registration of each slab you are looking at is not necessarily exactly the same. This is critically important so that you do not make treatment decisions based on the progression analysis of OCT angiogram images, which may not represent exactly the same slab. The importance of giving clinicians comparable images over time has not been lost on the manufacturers of OCT machines, all of whom are addressing this current problem. The ability to monitor the actual perfusion and size of CNVM complexes through therapy is an exciting opportunity that OCT angiography offers us that will be thoroughly studied over the next few years.

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