Microaneurysm Turnover May Predict Retinopathy Progression

Miriam E. Tucker

December 07, 2012

Automated analysis of microaneurysm (MA) turnover predicted the development of clinically significant macular edema (CSME) among patients with mild nonproliferative diabetic retinopathy (MNDR), according to results from a new study.

Maria Luisa Ribeiro, MD, from the Association for Innovation and Biomedical Research on Light and Image and the Faculty of Medicine, University of Coimbra, Portugal, and colleagues report their findings in an article published online November 30 in Diabetes Care.

"The most important message is that [MA] turnover, obtained in an automated fashion from fundus digital photographs, which is a simple noninvasive test, can identify the eyes/patients at risk of developing [CSME], the most frequent cause of vision loss due to diabetes," corresponding author José Cunha-Vaz, MD, PhD, told Medscape Medical News.

"Eyes/patients with nonproliferative retinopathy and repeatedly showing little disease activity (low [MA] turnover) may need less frequent eye care," he added. Dr. Cunha-Vas is emeritus professor of ophthalmology, University Hospital and University of Coimbra, and president of the Association for Innovation and Biomedical Research on Light and Image and the Faculty of Medicine.

Measuring MA Turnover

In this prospective observational study, the investigators used the RetmarkerDR (Critical Health SA) diagnostic system to measure the rates of MA appearances and disappearances from color fundus photographs. This dynamic measure, which reflects both the closing down of MA because of thrombosis and the appearance of new aneurysms in different locations in the vascular tree, was shown in a previous study by the authors to predict worsening of retinopathy to CSME.

In the current study, the investigators evaluated MA turnover in 410 patients (1 eye each) with type 2 diabetes who at baseline had MNDR. They were evaluated at baseline, at 6 months and then again either at 2 years or at the time of development of CSME requiring laser photocoagulation (study endpoint).

Of the 410 patients enrolled, 348 (84.9%) patients either developed CSME or were examined at 2 years. Of those, 26 (7.5%) developed CSME during the 2-year period and received laser treatment.

The eyes that developed CSME had an average of 6.2 MA (± 5.4) compared with just 3.3 (±3.7) among the 322 eyes that did not develop CSME. That difference was significant (P < .001).

In a multivariate analysis accounting for baseline parameters including age, sex, diabetes duration, blood pressure, best corrected visual acuity, and central retinal thickness, the rate of MA turnover in the first 6 months independently predicted development of CSME. The eyes that developed CSME had a MA turnover of 11.2 (± 11.2) vs 5.0 (± 5.2) for those that did not (P < .001).

An MA turnover cutoff value of 9 or greater had a sensitivity of 57.7% and a specificity of 81.2% for predicting CSME within 2 years. Eyes with an MA turnover greater than 9 during the initial 6 months had nearly a 6-fold higher risk of developing CSME compared with eyes that had a lower turnover (odd ratio, 5.886; 95% confidence interval, 2.503 - 13.844).

The negative predictive value, 95.9%, demonstrated that "a low MA turnover value is associated with less likelihood for CSME development in a 2-year period," the authors write.

A higher hemoglobin A1c value was the only other significant predictor of progression to CSME among the other parameters analyzed (P = .022).

Clinical Use

Dr. Cunha-Vaz told Medscape Medical News that the RetmarkerDR could be used to annually screen patients to identify those at higher risk who might need closer monitoring. "By promptly identifying the eyes/patients at risk for vision-threatening complications, it is possible to treat earlier — as soon as the complication develops. These cases will respond better to therapy, thus avoiding late treatment associated with more complex and expensive therapies."

In addition, "It is expected...this tool [will create] a more efficient information flow between screeners, primary care physicians, diabetologists, and ophthalmologists[, ensuring] earlier and timely referrals."

According to Paolo Antonio S. Silva, MD, instructor in ophthalmology at Harvard Medical School and the Beetham Eye Institute of the Joslin Diabetes Center, Boston, Massachusetts, "This is an interesting study and potentially may support the use of predictive algorithms and retinal imaging to identify progressive retinal disease in both clinical and research settings."

In addition, Dr. Silva told Medscape Medical News, the study findings are in line with previous studies demonstrating the significance of the relationship between both MA counts and MA turnover and retinopathy progression.

However, he cautioned that 2 years is not sufficient follow-up. "The paper by Ribeiro et al is limited by the short duration of follow-up. The rates of progression in type 2 [diabetes] patients with mild [MNDR] is low; thus, longer and more definitive follow-up studies will be needed to establish broad clinical acceptance of this observation and technology."

The RetmarkerDR is not currently available in the United States, but Critical Health plans to pursue the US market, according to Dr. Cunha-Vaz.

Financial support came from Fundação para a Ciência e a Tecnologia, Portugal. Dr. Cunha-Vaz is a consultant at Allergan, Alimera Sciences, Bayer, Critical Health, Fovea Pharmaceuticals, Gene Signal, Novartis, Pfizer, and Roche. The other authors and Dr. Silva have disclosed no relevant financial relationships.

Diabetes Care. Published online November 30, 2012. Abstract