Retina experts reach consensus on inflammation and Iluvien in DME
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Consensus statements provide useful guidance on current clinical practice patterns and disease pathophysiology in an ever-evolving landscape of patient care.
An expert consensus was recently published by Kolomeyer and colleagues to gain insight into current understanding of the role of inflammation in diabetic macular edema pathophysiology and the efficacy and safety of the 0.19 mg fluocinolone acetonide (FAc) implant, Iluvien (Alimera Sciences).
Expert surveys of this type provide an important snapshot of our understanding of DME and clarify where the FAc implant fits in with the current standard of care. They also consider the broadly held beliefs of the pros and cons of utilizing such a therapy. Among the co-authors, all recognized expert retinal physicians, a list of 12 consensus statements were generated and distributed to retinal physicians across the United States. Except for two multiple-choice, multiple-answer questions, physicians were asked to indicate their level of agreement or disagreement for each statement. In total, 56 retinal physicians responded to the survey, and the aggregate results determined whether consensus was reached or whether disagreement remained within the field.
Of the 10 consensus statements that ranked the level of agreement or disagreement, seven reached the consensus threshold of more than 80% agreement among physicians. These included statements on the role of inflammation in DME pathophysiology, injection burden and retinal thickness variability, as well as efficacy and safety of the FAc implant.
Broadly speaking, physicians agreed that poor glycemic control leads to production of inflammatory cytokines that cause retinal inflammation and are ultimately the key drivers of diabetic retinopathy (DR) and DME pathogenesis and retinal neurodegeneration. Along these lines, there was consensus that steroids have broad, nonspecific, anti-inflammatory properties that can downregulate pathological cytokine levels, including VEGF.
When it came to current standard of care, physicians agreed that the high injection burden, necessitated by short-acting therapies, leads to patient fatigue and noncompliance. They agreed that therapy nonadherence limited treatment efficacy and can result in increased amplitude and frequency of retinal thickness fluctuations, which may cause irreversible vision loss.
Conversely, physicians agreed that the Iluvien implant can minimize retinal thickness fluctuations while also reducing treatment burden compared with the current standard of care. Regarding IOP elevations with the implant, the most common side effect of corticosteroid use in the eye, physicians agreed that these were manageable in most cases through topical IOP-lowering medications.
The expert consensus also generated two multiple-choice, multiple-answer statements that attempted to gain further understanding of which clinical scenarios justified steroid use as baseline therapy and which steroid delivery routes satisfy the corticosteroid challenge that is part of the label of the Iluvien implant. Fifty-five percent agreed that any patient with DME could benefit from corticosteroids as a baseline therapy, while 7% indicated that they do not think it is appropriate at all. However, 73% agreed that pseudophakic patients best fit this category. Physicians surveyed unanimously reported that intravitreal steroid delivery was an appropriate form of steroid challenge, with 73% indicating sub-Tenon’s/periocular and 57% indicating topical as their preferred steroid delivery route.
Although seven of 10 statements reached consensus, three statements did not reach the more than 80% agreement threshold predefined by the study. All three statements largely reflected the use of the FAc implant or the steroid challenge required by its label. Physicians did not reach consensus that the implant can delay DR progression or reduce the DR severity score. They also did not find consensus that the implant represented a viable treatment option to establish baseline control of chronic inflammation in both DR and DME. Lastly, consensus was not found that the corticosteroid challenge reduces the risk for IOP-related events with the FAc implant.
To find further support to these statements, two studies were undertaken to provide relevant clinical data to help guide practice patterns in the future. The first, the recently fully enrolled New Day study, aims to evaluate the Iluvien implant as a first-line therapy option for DME and evaluate the number of aflibercept injections required when compared with the aflibercept-treated arm. Among the many secondary endpoints to be evaluated, the study will also determine the implant’s ability to delay DR progression and reduce the DR severity score.
The second study, PALADIN, a phase 4 open-label observational study that was recently published, looked at the real-world safety of the FAc implant for DME. Although not agreed upon in this survey, it provided evidence that the corticosteroid challenge does mitigate risk to potential IOP events when compared with rates of the registration trial, FAME.
Most retina specialists appear to understand the significance of inflammation in the pathophysiology of DME and DR. Despite some lingering questions, significant progress has been made regarding the acceptance and benefit associated with the FAc implant, bringing us closer to a complete understanding of its role in the treatment of diabetic eye disease. The New Day study will help to provide greater clarity to the retina community regarding the utility of the FAc implant as a baseline therapy for DME while also examining its ability to reduce treatment burden, reverse DR severity and potentially limit neurodegeneration.
- References:
- Campochiaro PA, et al. Ophthalmology. 2012;doi:10.1016/j.ophtha.2012.04.030.
- Kolomeyer AM, et al. Ophthalmic Surg Lasers Imaging Retina. 2023;doi:10.3928/23258160-20230215-01.
- Riemann CD, et al. Ophthalmic Surg Lasers Imaging Retina. 2020;doi:10.3928/23258160-20200501-09.
- Singer MA, et al. Ophthalmology. 2022;doi:10.1016/j.ophtha.2022.01.015.
- A study of intravitreal Iluvien implant as baseline therapy in patients with early diabetic macular edema (DME) (NEW DAY). https://www.clinicaltrials.gov/study/NCT04469595. Updated June 26, 2023. Accessed July 24, 2023.
- For more information:
- Ashkan M. Abbey, MD, of Texas Retina Associates, can be reached at ashkanabbey@gmail.com.
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