Rosacea Blog

Now that the full paper is published online, this post looks in more detail at topical dobesilate. You can see our previous dobesilate post here, which is also worth reviewing.

This is a paper describing a case study of person's response, so that needs to be kept in mind when looking at the results. Here is a link to the full paper, in PDF format, with colour photos:

Theraputic Response of Rosacea to Dobesilate

That caveat in mind, here are some of my thoughts along with some key quotes. For those interested I suggest reading the paper in full (it's only short!), if only for the description of angiogenesis in normal and diseased states. There are also a bunch of references you can follow up.

Quote:

"Photographs were taken before and after study completion. Compliance was judged to be good because of the patient's high motivation. As Figure 1 shows, topical dobesilate led to a significant improvement in erythema and telangectasia. Furthermore, the symptoms of flushing, burning and stinging sensations were all reduced after treatment, with no recurrence four months after stopping the therapy."

I am not 100% convinced by the photos (contrast/brightness does not appear consistent before/after and the flash used does not appear to have been diffused on either photo, so there is skin whitening), but they do appear to show reduction in redness. I cannot make out any individual telangiectasias in the PDF document photos, but that is what is being reported before but reduced after. What is most interesting is the reported long-lasting benefits on flushing, redness and stinging – the most troublesome and hard to treat aspects of this vascular disorder. This fits in well with the following quote.

Quote:

"In addition, FGF acts synergically with VEGF in the induction of angiogenesis probably by upregulating VEGF and VEGF receptors in endothelial cells [29-31]. Recently it has been reported that FGF, together with VEGF, contributes to tumor angiogenesis and that inhibition of their activities halts tumor growth [32]. Thus, therapeutic approaches based on the inhibition of FGF function may allow the simultaneous targeting of different cell types. Moreover, such treatment may potentiate the inhibition of VEGF function in cases in which both factors are expressed and act in a synergistic manner."

So, FGF inhibition (dobesilate is an FGF inhibitor) may also have effects on inhibiting VEGF. These are two of the major causes of angiogenesis, so you get a 2-for-1 effect!

Quote:

"Local inhibition of angiogenic factors function by dobesilate may prevent skin angiogenesis and inflammation in rosacea and other angiogenesis-dependent skin diseases in which a dense network of new vessels is produced and inflammatory cells are present. This molecule may also play a role in the reduction of inflammation [33] by regulating the synthesis of inflammatory molecules in rosacea. Furthermore, since FGF acts as survival factor for many cell types including endothelial cells [34, 35], it is likely that inhibiting FGF function by dobesilate [21] represents a biological relevant mean of producing apoptotic endothelium in rosacea vessels."

My understanding is that the paper is proposing that topical application of this angiogenesis inhibitor, dobesilate, may actually be a method of reducing the dense capillary network that is at the heart of rosacea, as well as producing a positive effect on inflammation reduction.

I would like to raise the following questions:

Could topical dobesilate stop the long-term progression of this disease early on in the disease process?

Could topical dobesilate applied post IPL or vascular laser, reduce post-laser angiogenesis and reduce the number of treatments needed and the effectiveness of those treatments?

Could topical dobesilate be useful on the eyelids and around the eyes to treat angiogenesis and telangiectasia that many doctors won’t/can’t treat with IPL.

What, if any are the long-term dangers of applications of topical dobesilate?

Can the results reported in this paper be replicated in larger studies?

What are the before/after blood flow readings with laser Doppler on the cheeks after topical dobesilate in a split-face study – it is a shame this was not performed in this paper

Hopefully a larger study can be performed with this promising topical molecule!

The full paper by P Cuevas et. al is now online as a PDF download:

Theraputic Response of Rosacea to Dobesilate

We have blogged about rosacea and topical dobesilate before, here.

I will post more analysis when I've read the paper in full, so please check back.