Intravitreal Steroids in Diabetic Macular Edema.Macular edema, a condition usually associated with an underlying disease process, is a common cause of severe visual loss. There have been a variety of approaches testosterone pills for men over the counter the treatment of macular edema; within the steroids macular edema few years, however, intravitreal corticosteroid treatments have emerged as an increasingly used treatment option for patients with macular edema. Intravitreal delivery allows the steroid to bypass the blood-retinal barrier, leading to a more concentrated dose of steroid for a prolonged period of time. Corticosteroids steroids macular edema likely been successful in the treatment of steroids macular edema forms of macular edema, due to their known anti-angiogenic, anti-edematous, anti-inflammatory, anti-apoptotic, and anti-proliferative effects. Intravitreal triamcinolone acetonide has been repeatedly successful in reducing macular edema and improving visual acuity, although the duration of action is typically short-term.
Intravitreal steroids for macular edema: the past, the present, and the future. - PubMed - NCBI
Diabetic macular edema is the most common cause of visual impairment in patients with diabetes mellitus. The pathogenesis of macular edema is complex and multifactorial. For many years, laser photocoagulation has been considered the standard therapy for the treatment of diabetic macular edema; however, few patients achieve significant improvements in visual acuity.
Today the intravitreal administration of anti-inflammatory or anti-angiogenic agents together with the use of laser photocoagulation represents the standard of care for the treatment of this complication. The intravitreal route of administration minimizes the systemic side effects of corticosteroids. Steroid-related ocular side effects are elevated intraocular pressure and cataract, while injection-related complications include endophthalmitis, vitreous hemorrhage, and retinal detachment.
In order to reduce the risks and complications, intravitreal implants have been developed recently to provide sustained release of corticosteroids and reduce repeated injections for the management of diabetic macular edema. In this review, the efficacy, safety, and therapeutic potential of intravitreal corticosteroids in diabetic macular edema are discussed with a review of recent literature.
Diabetic macular edema DME is the leading cause of vision loss in patients with diabetic retinopathy DR. Although the rate of serious vision loss due to DME is believed to have fallen in recent years, an additional 12,, new cases are reported each year. Grid and focal laser photocoagulation have long been accepted as the standard treatment for vision loss associated with DME.
It has been shown that laser photocoagulation reduces the risk of moderate vision loss in DME; however, many patients are unable to regain lost vision and the procedure is not effective in all DME patients.
With the development of intravitreal agents such as anti-vascular endothelial growth factor anti-VEGF and steroids, new strategies are now recommended for the management of this complex disease. While intravitreal implantation offers potential visual gains compared to laser interventions, repeated application confers risks in terms of both drug- and surgery-related side effects.
This review discusses the pathogenesis of DME, the rationale behind the use of corticosteroids, and current approaches to steroid use in the management of DME. The pathogenesis of DME is complex and multifactorial. DME forms as a result of fluid accumulation in the retinal layers due to disruption of the blood-retina barrier BRB.
Hyperglycemia is the main risk factor for DR. Hyperglycemia causes high intracellular glucose levels, free radical production due to oxidative stress, and activation of protein kinase C. Chronic hyperglycemia leads to the formation of advanced glycation end products.
Advanced glycation end products in the vitreous and vitreoretinal interface are responsible for the neurovascular damage seen in DR. The nervous and vascular systems are parallel systems in embryonic development. The two systems support each other during the formation of the vascular and nerve structures. Microvascular leakage and neuronal apoptosis occur in a mutual interaction.
Other causes such as hypoxia, impaired blood flow, retinal ischemia, and inflammation are also associated with the progression of DME. Elevated VEGF levels, endothelial dysfunction, leukocyte adhesion, reduced levels of pigment epithelium-derived factor, and increased protein kinase C production lead to BRB destruction and increased vascular permability.
VEGF is a homodimeric glycoprotein which stimulates vascular endothelial cell proliferation and increases vascular permeability. VEGF-A stimulates microvascular leakage and neuronal apoptosis, and is critical in the neurovascular unit.
There are many studies demonstrating the role of inflammation in the development of DR. Research on steroids in the treatment of DME has been ongoing for many years due to their powerful antiinflammatory and antiedematous effects. Corticosteroids block the arachidonic acid pathway via phospholipase A2 inhibition.
This inhibits the synthesis of thromboxanes, leukotrienes, and prostaglandins, and prevents vasodilation and increased capillary permeability. Corticosteroids also stabilize lysozymes, reduce synthesis of inflammatory mediators and VEGF, inhibit cell proliferation, stabilize the BRB, enhance the density and activity of tight junctions in the retinal capillary endothelium, and improve retinal oxygenation.
Significant decreases in retinal thickness have been observed within 1 hour of intravitreal triamcinolone acetonide IVTA injection, though no change was seen with bevacizumab after 24 hours. Endogenic adenosine release activates A1 receptors and opens glial potassium and chloride channels. The outflow of ions stabilizes the osmotic gradient and prevents cellular swelling. IVTA also stabilizes Starling forces by reducing vasoconstriction and hydrostatic pressure. The limited visual gains in those patients was believed to be related to neural damage, retinal pigment epithelium changes, and subretinal fibrosis resulting from chronic macular edema mean duration, 4.
Nonresponse to anti-VEGF therapy can be defined as a lack of anatomic improvement or the recurrence of retinal exudation when the interval between injections is extended. Steroid therapy should be considered in such cases. Intravitreal steroid injections reduce DME and stabilize vision, but side effects are common. The most common side effects are elevated intraocular pressure IOP and cataract formation. Therefore, steroids are preferable in pseudophakic eyes that have persistent or recurrent disease.
Steroid therapy for DME is administered as peribulbar injection, intravitreal injection, or intravitreal implant. There are currently three different intravitreal steroids utilized: TA is a synthetic steroid with five times the anti-inflammatory strength of hydrocortisone.
TA has a long-acting profile due to its low water solubility. The therapeutic effect of intravitreal 4 mg TA persists for up to 3 months. IVTA in suspension form is currently available as the following commercial preparations: At 2 years, mean BCVA was highest in the laser group, which was confirmed by central retinal thickness CRT measurements taken with optical coherence tomography.
Following the publication of the DRCR. Patients were randomly divided into 4 groups: Compared to the laser-only group, all 3 of the groups that received intravitreal injections showed significant and comparable decreases in CRT. Visual improvement in phakic eyes receiving IVTA was limited by the incidence of cataract. Currently, the intravitreal application of triamcinolone acetonide to treat DME is an off-label use.
For this reason, IVTA is recommended either alone or in combination with laser therapy in selected patients with persistent and refractory DME and vision loss, particularly pseudophakic patients. It is a biodegradable, sustained-release implant which remains effective for up to 6 months. The MEAD study was a 3-year, randomized, sham-controlled study evaluating the safety and efficacy of the 0.
The mean number of injections over 3 years was 4. The largest reduction in mean central macular thickness was observed in the 0. In terms of adverse effects, the rate of cataract development among phakic patients was IOP elevation was controlled in most cases with or without medication, but trabeculectomy was necessary for 2 patients 0.
When necessary, a second DEX implant or sham injection was given 6 months after the initial injection, and in both groups up to 3 supplemental laser applications were done at 3-month intervals.
The DEX implant and laser group showed a greater decrease in vascular leakage and retinal edema on angiography compared to the group treated with laser only. There was no significant differences between the groups in BCVA at 12 months. IOP elevation over 10 mmHg occured in At 12 months, 3. The study included 88 eyes of 61 patients with central DME. Forty-two eyes received pro re nata intravitreal bevacizumab every 4 weeks, and 46 eyes received a pro re nata DEX implant injection every 16 weeks.
Mean number of injections over 12 months was 8. Mean increase in BCVA was 6. The study demonstrated that in vitrectomized eyes with refractory DME, the DEX implant had an acceptable safety profile and provided statistically and clinically significant visual gains as well as reduced vascular leakage. Retisert is a nonbiodegradable implant containing 0. It is implanted through a pars plana incision and sutured to the sclera and continuously releases the drug for up to 30 months. After surgical implantation, it initially releases the steroid at 0.
In a multicenter study investigating the safety and efficacy of Retisert in the treatment of persistent and recurrent DME, patients were randomly assigned to receive either 0.
BCVA increased by 3 or more lines in Throughout the study, implanted eyes showed greater reductions in CRT when compared to the standard care group.
It is injected into the vitreous using a 25 G injector and releases 0. Three-year follow-up outcomes have been published for the multicenter, double-blind FAME study about the efficacy of Iluvien implant in patients with DME refractory to laser therapy.
Patients with DME who had received laser therapy at least once were randomly assigned to 3 groups: Visual gains of 15 letters or more were reported in In addition, subgroup analysis was conducted to investigate the effect of DME duration on treatment.
However, this difference was not significant among patients with DME for less than 3 years. Although all of the patients treated with IVFA developed cataract, their visual gains after cataract surgery were comparable to those of pseudophakic patients. After 3 years, incisional glaucoma surgery was required in 4. Intravitreal administration of corticosteroids reduces their systemic side effects and confers several advantages in the treatment of DME.
Because anti-VEGF agents are administered at frequent intervals, treatment costs are high. Sustained-release steroid implants reduce the number of intravitreal injections and greatly lower the risk of endophthalmitis and traumatic cataract.
However, the risk of developing corticosteroid-induced cataract is extremely high. Although there is better patient compliance with the IVFA implant because its duration of effect is longer than the DEX implant, but it has also been associated with higher risk of ocular hypertension and cataract. However, no clinical studies directly comparing the two treatment methods have been conducted to date.
Laser photocoagulation is preferable in patients with noncentral DME due to the low risk, low cost, and patient compliance in this group. The duration of effect is longer, and the injection number and follow-up frequency are lower than with anti-VEGF treatment.
Therefore, particularly in chronic diffuse macular edema, steroid therapy is preferable for patients who do not respond to anti-VEGF therapy, or who have conditions contraindicated for anti-VEGF therapy such as recent cerebrovascular event or myocardial infarction. Due to the short half-life and probable low efficacy of anti-VEGF agents, steroid implants may be appropriate as initial treatment in vitrectomized patients with central DME. Corticosteroid implants are suitable alternatives to anti-VEGF therapy for pseudophakic patients with persistent central DME who do not have significant risk of glaucoma.
In addition to monotherapies, the long duration of effect of corticosteroid implants may enable combination therapies. However, clinical studies are still needed to evaluate the synergistic effects of these implants used in combination with laser and anti-VEGF agents.