The most common cause of vision loss in diabetic patients is diabetic macular edema, a disease that continues to grow to epidemic proportions due to the steady rise of diabetes prevalence in the United States. Standard ocular therapy for DME typically involves anti-VEGF (vascular endothelial growth factor) treatments, given that VEGF plays a key role in the advent of DME. Other pro-inflammatory factors, however, may also be involved. For the significant number of patients who suffer from persistent DME despite anti-VEGF treatments, corticosteroids are becoming a highly beneficial treatment option with viable results. However, there are several steroid options from which to choose when designing our treatment regimens for patients with DME.
The ocular steroids most commonly used — dexamethasone, triamcinolone acetonide, fluocinolone acetonide, difluprednate, and prednisolone acetate — all have slightly different chemical compositions and potential efficacy. These are differentiated by two main factors: penetration and delivery. When it comes to penetration, the drug’s water vs. lipid solubility determines how well it will be absorbed into targeted ocular tissues. The less water soluble (and more lipid soluble), the better it penetrates and thus a lower dose is needed for the desired result. Dexamethasone, for example, is highly water soluble and does not penetrate the retina well; rather, it mostly remains in the vitreous, thus requiring higher ocular concentration and more frequent dosing to achieve its efficacy. Triamcinolone acetonide, fluocinolone acetonide, difluprednate and prednisolone acetate are highly lipophilic (lipid soluble), which allows for better tissue penetration to the retina and trabecular meshwork, providing higher levels of clinical efficacy at the desired target sites (retina) with lower drug concentration.
The delivery system is also an important determining factor for drug efficacy. Several medications that are not indicated specifically for DME are commonly used off-label to treat it. However, topical medications such as Durezol (difluprednate, Alcon) and Pred Forte (prednisolone acetate, Allergan) may have less anti-inflammatory effect as they are not able to achieve a suitable concentration to the target retinal tissues. Others such as triamcinolone (Triesence, Alcon) can be injected, which aids in reaching the desired target area but requires frequently repeated injections for effective therapy. These medications all have varying degrees of efficacy and benefits, but all require multiple office visits which can become a burden for patients.
Sustained release medications can offer relief from frequent office visits, although patients will still require regular follow-up. Ozurdex (dexamethasone, Allergan) utilizes a type of injectable biodegradable pellet that is dissolved over several months. Iluvien (fluocinolone acetonide, Alimera Sciences) is also an injectable option; however, its delivery system utilizes a non-biodegradable implant that measures 3.5 mm in length and 0.37 mm in diameter. This implant remains in the eye and delivers continuous microdosing of the medication. This continuous delivery inhibits inflammatory responses and provides continuous and consistent treatment in safe and effective concentrations, with proven efficacy for up to 3 years.
One potential concern with steroid use is the development of ocular hypertension or sudden pressure spikes and, for some, this fear may be heightened with a product that is continuously releasing medication. However, in the clinical trials, the majority of patients using Iluvien did not develop IOP rises and most of the few who did were adequately controlled with IOP lowering medication.
For patients who respond well to steroids, I offer Iluvien as a standalone monotherapy to help treat their DME on a daily basis. For patients needing a combination therapy, Iluvien is utilized as a foundational steroid to give them microdosing on a daily basis, which is supplemented with anti-VGEF treatments if needed.
Steroid IOP challenge can be conducted with intravitreal steroid or topical steroids such as prednisolone acetate or difluprednate four times a day in the potential eye for up to 4 to 6 weeks. This helps to properly screen the patient so as to minimize risks of any sort of IOP spike that may indicate the patient is a steroid responder. Additionally, patients who have had an Ozurdex treatment or steroid treatment as part of cataract surgery in the past and did not have a clinically significant rise in IOP can be considered good candidates for Iluvien.
For patients who need continuous control over DME, Iluvien provides sustained-release microdosing delivery as a safe and effective option, as well as patient treatment burden relief from frequent eye injections and office visits. The peace of mind that comes from knowing inflammation and edema are being consistently and safely treated is invaluable for both physician and patient.
ALOGPS, also reported to have extremely low water solubility in patent EP 0878197 A1.
ALOGPS, also reported as practically insoluble in water in patent EP1909798 A2.
Boyer DS, et al. Ther Adv Endocrinol Metab. 2013;doi:10.1177/2042018813512360.
Campochiaro PA, et al. Ophthalmology. 2012;doi:10.1016/j.ophtha.2012.04.030.
Campochiaro PA, et al. Ophthalmology. 2010; doi:10.1016/j.ophtha.2009.11.024.
Dugel PU, et al. Clin Ophthalmol. 2015;doi:10.2147/OPTH.S79948.
Elman MJ, et al. Ophthalmology. 2011; doi:10.1016/j.ophtha.2010.12.033.
Florey K, ed. Analytical Profiles of Drug Substances. Vol 11. New York, NY: Academic Press. 1982:620.
Holekamp NM. Am J Manag Care. 2016;22:S284-S291.
Lee R, et al. Eye Vis (Lond). 2015;doi:10.1186/s40662-015-0026-2.
O’Neil MJ, et al, eds. The Merck Index: An Encyclopedia of Chemicals, Drugs, and Biologicals. 13th ed. Whitehouse Station, NJ: Merck and Co; 2001:518.
Romero-Aroca P, et al. J Diabetes Res. 2016;doi:10.1155/2016/2156273.
Wells JA, et al. N Engl J Med. 2015; doi:10.1056/NEJMoa1414264.
Osol A, et al, eds. Remington’s Pharmaceutical Sciences. 15th ed. Easton, PA: Mack Publishing Co; 1975:892.
Joshua Mali, MD, is a board-certified ophthalmologist and award-winning vitreoretinal surgeon at The Eye Associates, Sarasota, Florida.
Disclosure: Mali reports he is a consultant, speaker and stock shareholder for Alimera Sciences, a consultant for and recipient of research funding from Allergan, a consultant and speaker for Genentech, a consultant, speaker and stock shareholder for and recipient of research funding from Regeneron, a consultant and speaker for and recipient of research funding from Notal Vision, a consultant and speaker for Sun Pharmaceutical Industries, and a consultant and speaker for Macular Degeneration Association.