In medicine, we use the term occult when we know disease exists but there are no readily discernable signs. In this issue, we discuss a “new” entity termed nonexudative macular neovascularization (neMNV). While the term is new, the entity is not, as this neovascularization has been occult all along.

When I was in high school, the landmark Macular Photocoagulation Study (MPS) Group coined the term occult choroidal neovascularization to describe a fluorescein leakage pattern that was either a type 1 fibrovascular pigment epithelial detachment with early, irregularly elevated, stippled hyperfluorescence with late leakage or late leakage of undetermined origin (type 2). The classification depended on 3-dimensional stereo evaluation of a fluorescein angiogram. Because occult CNV did not benefit from laser, natural history studies could be performed that showed an approximate conversion rate of approximately 25% to 30% to classic CNV with almost half of the patients having no change in vision. Many patients with occult-only CNV never lost vision or had disease progression to classic CNV.

The term occult persisted in the photodynamic therapy pivotal trials where occult CNV could be enrolled in the Verteporfin in Photodynamic Therapy Study (VIP Study) only in the presence of disease progression. Disease progression was defined as (1) presence of blood associated with CNV; (2) visual acuity deterioration of at least 5 letters within the past 12 weeks; or (3) an increase in the greatest linear dimension of the lesion of at least 10% within the past 12 weeks. This definition carried over in the pivotal MARINA study (Minimally Classic/Occult Trial of the Anti-VEGF Antibody Ranibizumab in the Treatment of Neovascular AMD) for ranibizumab. Occult CNV required disease progression to be enrolled.

Only with the pivotal VIEW studies of aflibercept was disease progression dropped as an inclusion criteria for occult CNV. Our collective memories are short, and so the idea of waiting for disease progression in occult lesions was lost and many retina specialists treat occult without waiting for disease progression. Moreover, multimodal imaging has led us to change our classification of CNV. Occult CNV is best described as a type 1 lesion below the retinal pigment epithelium.

In the digital age, we almost never evaluate fluorescein angiograms in 3 dimensions with a stereo viewer. It is a lost art. In fact, we almost never use fluorescein angiography in wet AMD. Everything is based on OCT. With the advent of OCTA, we can now decide if a double-layer sign is truly a type 1 CNV or just some amorphous drusenoid debris. We now have a term for this early, occult lesion: neMNV. Authors debate whether this early CNV should be treated. But, we already know the answer … we have for years. RP