DIABETIC MACULAR OEDEMA

Patients with longstanding diabetic macular oedema appear to have a stronger response to treatment with a low-dose fluocinolone acetonide implant (Iluvien®, Alimera) than do patients who have had the condition for only a short time, according to a subgroup analysis of participants in the two FAME (Fluocinolone Acetonide in Macular Oedema) trials, presented at the 22nd Meeting of the European Association for the Study of Diabetes’ Eye Complications Study Group (EASDec). “A significant benefit-to-risk ratio has been demonstrated in this sub-population of patients with chronic diabetic macular oedema. This finding is the basis of the approval of Iluvien in the UK. Its approved indication is for the treatment of visual impairment due to chronic diabetic macular oedema that is insufficiently unresponsive to available therapies,†said Abosede Cole MD, Bristol Eye Hospital, UK, who presented the study’s findings.

The new implant is injected into the eye using a 25-gauge injector, she noted. The FAME studies included 956 patients randomised on a two-to-two-to-one basis to receive 0.5 microgram insert, 0.2 microgram insert or sham injections. Dr Cole noted that the patients in the three treatment groups were well balanced in terms of age, sex and disease characteristics. Overall, the mean duration of their diabetic macular oedema was 3.79 years and all had undergone at least one prior laser treatment. Furthermore, in all of the patients involved in the study, the oedema involved the central macula and central retinal thickness was 250 μm or more. The mean centre-point thickness in all three groups was well in excess of 400 μm, she said. The patients’ best-corrected visual acuity prior to treatment was 19 to 68 letters, she added. 

Lower dose better

Dr Cole noted that the FAME study achieved its primary endpoint. That is, at two years’ follow-up, the proportion of patients achieving an improvement from baseline of 15 or more ETDRS letters was 28.7 per cent in the low-dose group and 28.6 per cent in the high-dose group. That compared to only 16.2 per cent in the sham group injection group (P = 0.002). There were significantly greater improvements in visual acuity in the Iluvien treated patients than in the sham injection patients from three weeks after commencing therapy, she said. As regards side effects, 75 per cent of phakic patients in both Iluvien-treated groups required cataract surgery. However, the visual benefit those patients achieved after surgery was similar to that of those who were pseudophakic at baseline. Around 40 per cent of the patients required some intraocular pressure medication, Elevated ocular pressure requiring incisional surgery occurred in 4.8 per cent, 7.6 per cent, and 0.5 per cent of the low-dose, high-dose and sham groups, respectively. The results indicated that both dosages were equally effective, although the lower dosage had a superior safety profile, she noted. “This raised the question of whether there was a specific subgroup of diabetic macular oedema patients who had a better risk-benefit ratio. If such a subgroup did exist there would have to be a statistically significant better visual acuity outcome at 24 and 36 months and this subgroup should be identifiable prior to the use of Iluvien,†Dr Cole said.

The Fame study investigators therefore divided the entire patient population into two subgroups. One group included 536 patients whose diabetic macular oedema had been present for three years or longer at baseline, which they labelled chronic diabetic macular oedema, and the other group included 416 patients whose diabetic macular oedema had been present for less than three years. 

Effect most pronounced in chronic patients 

The new subgroup analysis showed that, among patients who had diabetic macular oedema for longer than three years, 34 per cent of those receiving the 0.2 micrograms per day version of the implant had an improvement of 15 or more letters of best-corrected visual acuity, compared to only 13.4 per cent of controls (p<0.001). By comparison, among the total group the proportion of those receiving the low dose implant achieving a 15-letter gain was only 28.7 per cent, and that of the controls was 16.2 per cent. “The reason for this is not well understood, there are various hypotheses which haven't yet been proven. It may be that the role of inflammation may be more important in patients who have had diabetic macular oedema for longer. However, that is just a hypothesis,†Dr Cole said. The main safety issue of the implant, as with all steroids, is its potential to cause glaucoma, she said. However, although intraocular pressure elevation did occur, it did not diminish the visual acuity outcomes even among those patients who required surgery, she said.

“A sustained dosage of 0.2 micrograms per day of fluocinolone acetonide provided rapid and sustained improvement in best corrected visual acuity and retinal thickness in patients with diabetic macular oedema for up to 36 months. The greatest benefit was seen in patients with chronic diabetic macular oedema. The development of cataract was very common in the fluocinolone acetonide-treated patients and fewer than five per cent required incisional IOP lowering procedures,†Dr Cole added.