In this issue, Rabiolo et al. present optical coherence tomography angiography (OCT-A) and ultra-widefield (UWF) imaging of the involved and contralateral eyes of patients affected by Coats’ disease.

The quality of the images, descriptions of details, and completeness of the instrumental exams are superb. This is a recognized group of retinal experts, and they offer unmatched insight into 20 years [1] of clinical expertise.

I also worked for many years with one of the authors (FB), and in the early 1990s we routinely performed fluorescein angiography (FAG) of the sound eye in children affected by Coats’ disease, noting peripheral anomalies only sporadically. Our inclination to carefully observe the fellow eye was part of the standard of care, but also part of our speculative interest as scholars of the disease.

Having said that, I was impressed to see the figure showing sound eye peripheral involvement in this series—seven out of nine consecutive patients, which is by far higher than the 95% unilateral involvement reported in the most important series published by Shield & Shields [2] some years ago.

Looking carefully at the references, I found the Blair [3] paper, which lacked convincing evidence of frequent bilateral involvement. In that paper, the number of non-peripherally perfused sound eyes was similarly impressive (22 out of 32 patients), but a critical observation of the only two attached pictures indeed depicted extreme patients: the case in Fig. 1 showed a very mild evolution of Coats’ disease despite relevant vascular anomalies in an already 9-year-old boy, and conversely, the patient in Fig. 2 had an unusually severe exudative detachment for a 1-year-old girl, and beading vessels without leakage in the fellow eye. I must confess that, having dealt with several Coats patients, I needed further evidence before accepting Coats as any more than rarely a bilateral condition.

Coming back to the present study, which involved 11 patients, the mean age is greater than we would expect for this condition (17.1 ± 6.7 years), as the authors correctly admit, and this is something that makes the population examined atypical.

What worries me is that, if the reported figure is reliable, we are dealing with or handling conditions that do not fit perfectly in the spectrum of Coats’ disease, or my previous clinical evaluations could at least be considered inaccurate. In fact, what I neglected with FAG under anesthesia in past years actually still appears difficult to miss.

At the same time—and I thank the authors for this kind lifeline—UWF imaging is a user/patient-friendly technique, and although I hardly accept that telangiectatic vessels or non-perfused area (not in extreme periphery) were hidden to acute observers keen in this kind of evaluation, they authoritatively remind me that a new era of retinal exploration has begun, and I must rely on modern instruments more than on clinical experience… sadly, I have to agree with this.

Another important point is that, considering the age range, none of the bilaterally affected patients manifested significant sequelae related to the anomalies of the fellow eye, and this is consistent with the literature [2] and with my experience.

As scientists, we must continue to strive to clarify all the unclear aspects of a disease and persist in looking for answers when the questions are unresolved.

I concur with the authors that careful investigation of the fellow eye should be mandatory in Coats’ disease. At the same time, however, I urge scientists to avoid disproportionate alarmism, as a courtesy to the exhausted families of these unlucky children, avoiding overestimation of innocent aspects: if involvement of the fellow eye exists, further studies are needed to clarify how close the follow-up of the sound eye should be, and to what extent the disclosed anomalies represent a relevant clinical risk for the patient’s sight.

Finally, the authors reiterate a possible genetic background and propose the familial exudative vitreoretinopathy (FEVR) model, which shares the asymmetric expression with Duane’s disease.

As in many other diseases, I do not think there exists a clear boundary between genetic and non-genetic etiology in this condition: this is not familiar as FEVR or clearly gene-assigned as NDP in Norrie’s (a quoted anecdotal association [4] with this gene has not been confirmed by other studies, despite 20 years of investigation). Nevertheless, several observations of associated gene mutations support the possibility of Coats’ disease as a genetic syndrome. In my opinion, a more convincing analogue is another predominantly unilateral vascular anomaly whose pathogenesis is still controversial: the Sturge-Weber syndrome.

Two theories, both lacking in proof, overtook the old and evocative unifying dysembryogenetic concept of neurocristopathy: on one side, a post-zygotic somatic mutation resulting in mosaicism [5] (this will explain the unilateral phenotype in common with Coats’ disease), and on the other, a more mechanical hypothesis of an alternative venous outflow from the brain in the absence of cortical veins [6], that cause all the oculocutaneous sequence (and the variable spectrum element shared by Coats’ disease) of this condition.