Therapeutic apheresis slows the downhill course of dry AMD

By Stefanie Petrou-Binder MD

Nürnberg - A rheopheresis not only halts further visual loss, but may even improve visual acuity in patients with 'dry' age-related macular degeneration (AMD), according to a new study.
Richard Brunner MD, Centre of Ophthalmology, University of Cologne, reviewed the results of a retrospective historic four-year randomised study of the novel treatment modality and presented his results at the 15th Annual Meeting of German Ophthalmic Surgeons.

The protocol involved 20 eyes of the same number of patients. Patients underwent therapy which combined membrane-differential-filtration, selective adsorption, and plasma exchange. He carried out this treatment programme for three years in all 20 patients, with an annual average of six treatments, and for four years in 12 of the patients.

Some 15 of the 20 patients treated with apheresis had improved visual acuity after either two or three years of treatment.

These results verified Dr Brunner's previous six-month trial results. Of the 12 patients who received treatment for four years, seven had improved vision.
The average improvement in visual acuity after two years was 1.9 lines (p<0.05 on ETDRS-charts). After three years, the average improvement was 1.2 lines (p<0.05). And after four years, the average improvement was 0.8 lines among the 12 eyes treated for that duration ( p=0.77).

Although the visual improvement was insignificant after four years, compared to the acuity values assessed at the start of the study, Dr Brunner said it was noteworthy that there was also no further deterioration of visual acuity. This represents a success of sorts considering that the natural course of dry AMD is one of continuous and rapid vision loss, he said.

Dr Brunner reported that the team also observed a significant difference in the plasma and whole blood viscosity, as well as in erythrocyte aggregation properties over the course of the study.

Inspired by Dr Brunner's studies, US investigators conducted a multicentre phase III clinical trial to evaluate further the safety and efficacy of the therapeutic apheresis procedure for patients with dry AMD.

Twelve study centres participated in this randomised apheresis/placebo study (2:1 ratio) which included 150 AMD patients. Each patient admitted to the study had pre-angiogenic AMD, with an area of soft drusen =31,000 um2 , elevated blood levels of relevant haemorheologic factors, and early treatment diabetic retinopathy study (ETDRS) visual acuity between 20/32 and 25/125. The patients were monitored for one year.

The interim results were presented earlier this year by members of the Indiana University School of Medicine at the annual ARVO conference in Florida. The report included the observations made in 43 patients who completed their 12-month follow-up visit.
The interim analysis included three groups: all the study eyes (n=43); all the qualifying eyes that met inclusion criteria (study eyes and fellow eyes: n=54); and all eyes of all subjects (n=85).

The statistical analysis compared treatment and control groups of best corrected ETDRS visual acuity acquired at three, six, nine, and 12-month post-baseline visits.
At 12 months, all three groups demonstrated a significant change in acuity. The mean difference between the treatment and control groups was 1.6 ETDRS lines in the first group (p=0.001); 1.5 in the second all-qualifying group (p=0.005); and 1.7 in the third all-eyes group (p= 0.003).

The sub-group analysis showed that subjects with baseline acuity below 20/40 derived the greatest benefit at one year (mean difference 3.0 lines in study eyes at 12 months, p=0.001). In the first study group, 20% of the subjects had at least 2.5 lines of improvement, compared to only 9% in the placebo study group.

They said the mechanism of action was still under investigation but presumed that the positive effects were related to the haemorheologic and blood flow changes in the choriocapillaris, along with the removal of specific pathologic macromolecules from the plasma through extracorporeal blood filtration.

Functional reserve
According to present research, the retina seems to have a functional reserve in AMD patients. They react differently to therapy based on the individual reversible and irreversible morphological changes undergone by the retina. The goal of apheresis is to activate or stabilise this functional reserve.

Dr Brunner said these early clinical results were "encouraging". The findings are likely to stimulate further research into pathogenesis of the disease, the action mechanism of the treatment and the development of new treatment strategies, he commented.

"These developments are largely to be credited to the 14 or more years of medical research which we have done in this area at Cologne University. This very specific treatment programme was initiated by our team in Cologne and has included dating 1,400 treatments in 430 patients.

"Our results have appeared in 27 publications. This therapy is being adopted throughout Germany and abroad for patients with ocular diseases. With the co-operation of the Department of Internal Medicine, we have treated a number of different eye diseases with similarly encouraging results," Dr Brunner reported.
Therapeutic apheresis refers to extracorporeal treatments that are used to rid the blood of high molecular weight proteins and lipids.

Therapeutic apheresis-plasmapheresis involves removing a deleterious component of plasma. It is used to treat a variety of conditions including myasthenia gravis, thrombotic thrombocytopenic purpura and Guillain-Barre syndrome.
Cytapheresis, or cytoreduction, involves reducing the volume of blood cells. It is sometimes used to treat severe thrombocytosis in advanced leukaemia.

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