Multimodal imaging

Histology and multimodal imaging combination valuable in macular pathology. Dermot McGrath reports

When combined with histology, multimodal imaging has the potential to shed light on previously unelucidated or poorly understood anatomical features and disease mechanisms in agerelated macular degeneration, according to Rosa Dolz-Marco MD, PhD, FEBO.

“We are fortunate in that we now have a lot of imaging modalities with which to analyse our patients in detail. We can learn a lot from these images, but even more so when we can correlate them with histology to help us explain things we do not understand with imaging alone. The two approaches complement each other and help to fill in the information that we are lacking,” she told delegates attending the Young Ophthalmologists Programme at the 19th EURETINA Congress in Paris.

Dr Dolz-Marco, Oftalvist Clinic, Valencia, Spain, highlighted a number of areas in which histology combined with multimodal imaging has helped to answer some important questions concerning AMD and disease progression as part of a research project conducted by Dr Christine A. Curcio in the University of Alabama, and Dr K Bailey Freund at Vitreous Retina Macula Consultants of New York.

In macular atrophy, she noted that conventional thinking has been that choroidal hyper-transmission on OCT scans always correlated with the area of retinal pigment epithelium (RPE) atrophy. “OCT certainly provides us with valuable 3D information and enables us to detect early changes or signs of neovascularisation. In histology, however, the RPE does not always end in a clearly defined border, but the external limiting membrane (ELM) ends in a curved line that delimits the area of photoreceptor atrophy,” she said.

This curve or descent of the ELM, corresponding to the histologic border of photoreceptor atrophy, may serve as a useful marker of photoreceptor atrophy, she said.

“To determine ELM descent on OCT we need high-quality scans because they will not be visible on low-quality images,” she said.

In further studies, Dr Dolz-Marco and her co-workers were able to identify clear steps in outer retinal tubulation (ORT) formation by tracking the ELM descent and classifying its shape (flat, curved, reflected and scrolled) at the border of outer retinal and RPE atrophy. “This helped us to understand progressive steps in the development of ORT and to hypothesise that scrolling

EUROTIMES | APRIL 2020 ORT is usually a point of no return in order to develop advanced neurodegeneration of the macula with involvement of Muller cells. This kind of marker could be useful going forward in clinical trials in patients with macular atrophy,” she said.

Histology matched with OCT B-scans also proved valuable in revealing tissue features in geographic atrophy in an 86-year-old female patient, said Dr Dolz-Marco.

“The questions we wanted to answer in terms of the OCT scans related to the hyperreflective plaques over Bruch’s membrane, the presence of hyporeflective drusen and the hyporeflective wedgeshape,” she said.

The researchers concluded that the hyporeflective wedge shape corresponded to a reorganisation of Henle's fibre layer (HFL) and the outer nuclear layer (ONL), while the hyperreflective plaques located above Bruch’s membrane corresponded to cholesterol crystals. Finally, the hyporeflective drusen corresponded to multilobular

We are fortunate in that we now have a lot of imaging modalities with which to analyse our patients in detail Rosa Dolz-Marco MD, PhD, FEBO

Rosa Dolz-Marco MD, PhD, FEBO

calcific nodules, signifying the end stage of soft drusen and a marker for progression to geographic atrophy, she said.

Although not directly correlated with histology, multimodal imaging has also led to important new findings such as the choroidal caverns first described by Giuseppe Querques, said Dr Dolz-Marco.

Found relatively infrequently in eyes with geographic atrophy, the caverns appear as gaping angular hyporeflective cavities in areas devoid of choroidal vessels, often with punctate/linear hyperreflectivities internally. “The choroidal caverns are nonreflective spherical structures within the choroid with a posterior tail of hypertransmission with no evidence of flow signal on OCT-A and they match the lipid globules described by Friedman, which are extracellular, extravascular lipid in normal and AMD eyes, and are primarily choroidal but also located within neovascular membranes and sclera,” she said.

Histology allied to multimodal imaging also proved valuable in the case of an 84-year-old man with exudative aneurysmal type 1 (AT1) neovascularisation and haemorrhage secondary to age-related macular degeneration (AMD).

“We were able to show that in aneurysmal type 1 neovascularisation, the neovascularisation was located in the sub RPE-basal lamina space and has a choroidal origin,” she concluded.