PHENOTYPE FINDINGS

Different genetic polymorphisms appear to be associated with different phenotypes of non-proliferative diabetic retinopathy (NPDR), according to a study presented by José Cunha-Vaz MD at the 14th EURETINA Congress in London.

“It is known that diabetes causes neurodegenerative changes, and in the retina the microvascular response to the degenerative changes is different in different patients and is apparently genetically determined. Our study showed that different phenotypes of progression of NPDR have different risks for progression to clinically significant macular oedema (CSME),” he said.

Prof Cunha-Vaz, Emeritus Professor of Ophthalmology of the University of Coimbra, Portugal, noted that there are different risks for vision loss in different patients with similar metabolic control and duration of disease.

COMPLICATIONS

“As we try to look at why these patients develop complications, risk algorithms based on the diabetic disease are not necessarily completely foolproof. Because every one of us who has dealt in the clinic with patients with diabetes knows that some patients with excellent metabolic control who follow their physicians’ instructions may still develop CSME and potentially proliferative retinopathy, whereas other patients who are less careful never go on to develop macular oedema. It follows then that there is a need to identify causes from natural history studies,” said Prof Cunha-Vaz.

Prof Cunha-Vaz’s prospective study of 348 patients with NPDR and two years follow-up set out to examine the association of different candidate genes with different phenotypes of NPDR and risk for development of CSME.

Patients were classified in groups of three different phenotypes of retinopathy progression based on non-invasive methods: colour fundus photography to assess microaneurysm turnover using the RetmarkerDR (Critical Health SA, Coimbra, Portugal), and optical coherence tomography (OCT) to measure retinal thickness. The development of CSME was also addressed.

Eleven genes were selected from a list of candidate genes and their single nucleotide polymorphisms (SNPs) were filtered through bioinformatics tools.

Prof Cunha-Vaz said that three different phenotypes of NPDR with different risks for CSME were identified using Ward’s cluster analysis over the follow-up period.

Phenotype A was characterised by microaneurysm turnover of less than six and with normal retinal thickness; phenotype B was also characterised by a low microaneurysm turnover less than six, but with increased retinal thickness (greater than 220 microns); while phenotype C had a turnover greater
than six and variable thickness (153 to 297 microns).

Phenotype A can be characterised by slow progression with absence or low levels of leakage and microaneurysm turnover; phenotype B as “leaky” with increased retinal thickness on OCT scans; and phenotype C as “ischaemic”, a more rapid progressive type with increased microaneurysm turnover and active remodelling of the retinal circulation, explained Prof Cunha-Vaz.

“We found that after two years of follow-up, phenotypes B and C present a much higher risk for CSME development when compared to subjects in phenotype A. In the latter group, only one patient in 133 developed CSME, compared to eight out of 94 for phenotype B, and 17 in 121 for phenotype C,” said Prof Cunha-Vaz.

Summing up, Prof Cunha-Vaz said that there are different phenotypes of progression of NPDR which have different risks for CSME, and there is growing evidence of the association of specific SNPs for each specific phenotype.

José Cunha-Vaz: cunhavaz@aibili.pt