Research, published in the journal Ophthalmology, has reported that a post hoc analysis of data from the 36-month prospective, randomized FAME A and B Phase III trials in DME patients supports the use of the flucinolone acetonide (FAc) implant. The analysis shows that the controlled delivery corticosteroid slows development and progression of disease and may provide a treatment regimen with a reduced burden to the patient, ultimately leading to improved patient compliance and clinical management. The study aimed to investigate the effects of FAc on proliferative diabetic retinopathy (PDR) and the effect of changes on the diabetic retinopathy (DR) severity scale (DRSS) grade during the same FAc clinical trials.
The FAME A and B randomized, controlled, phase III trials reported on the outcome for DME patients receiving an intravitreal 0.19 mg FAc implant, designed to provide sustained low-dose steroid exposure following a single injection. The trials, conducted on 956 subjects with persistent DME with at least 1 prior macular laser photocoagulation treatment, comprised three treatment groups, 0.2 or 0.5 ug/day FAc intravitreal implant, or a sham injection. At the 36-month end-point, participating patients had received a mean of 1.3 to 1.4 treatments, with FAc patients showing a significant improvement in visual function (27.8% to 28.7%), compared to the sham group (18.9%). The majority of trial participants (70.7% to 74.4%) required only a single implant over the 36-month period. Patients with greater than the median duration (3 years) of DME showed an even more pronounced benefit in visual function, a 28.8% to 34.0% improvement among FAc-treated patients, compared to 13.4% in sham-treated subjects.
The study assessed progression to PDR based on three clinical outcomes including (a) progression from nonproliferative diabetic retinopathy (NPDR) to PDR, using graded fundus photographs; (b) panretinal photocoagulation, and; (c) pars plana vitrectomy (PPV) for PDR. The authors used a masked reading center to assess the DRSS grade and the retinal perfusion status using fundus photography and fluorescein angiography (FA), respectively. Analysis of the results showed that for FAc treated participants, the time to first PDR event was significantly delayed (P < 0.001) compared to sham control-treated subjects. A similar effect was observed in subgroups with more severe DR and chronic DME at baseline. The analysis also showed that pariticpants in the FAME studies with retinal nonperfusion at baseline showed more of a decrease in PDR progression when treated with FAc, compared to control treated patients. The study additionally showed that at time-points of 6, 12 and 18 months, patients treated with either dose of FAc had statistically significant improvements in their mean DR severity, while more subjects under-going FAc treatment had 2-or-more- or 3-or-more-step improvements in DR severity. While the rate of preventing progression to PDR was similar to that achieved with monthly anti-VEGF treatments, the FAc route may provide a treatment option that creates less of a patient burden. FAc however, is not without its own risks, including potential increases in IOP and cataract acceleration. Clinicians will undoubtedly need to continue to assess the optimal treatment plan on a patient-by-patient basis, weighing up the benefits, risks and compliance issues to optimise patient care.