Retina · Diabetic Retinopathy

Steroids in Diabetic Macular Oedema

Why corticosteroids work, where they fit in the treatment of diabetic macular oedema, and how to select the right patient and preparation.

Advanced retina companion note Persistent DME Intravitreal corticosteroids

This companion note updates and organises the clinical concepts discussed in the lecture, including persistent DME, patient selection, available corticosteroid preparations and the supporting evidence.

Why Inflammation Matters in DME

Chronic hyperglycaemia damages the retinal microvasculature and disrupts the blood–retinal barrier. Diabetic macular oedema is therefore driven by both a VEGF-mediated pathway and an inflammatory pathway.

Chronic hyperglycaemia

VEGF-mediated pathway

Increased VEGF weakens vascular tight junctions and increases retinal vascular permeability.

Inflammatory pathway

Cytokines, adhesion molecules and leukostasis further damage the vascular endothelium.

Blood–retinal barrier breakdown → retinal fluid accumulation → DME

Important mediators include interleukin-6, interleukin-8, tumour necrosis factor-α and monocyte chemoattractant protein-1. Increased expression of intercellular adhesion molecule-1 (ICAM-1) promotes leukocyte adhesion and leukostasis.

These inflammatory changes worsen endothelial dysfunction and impair normal retinal fluid regulation. This explains why corticosteroids can reduce oedema through mechanisms that extend beyond VEGF suppression. [1]

How Corticosteroids Act

Corticosteroids act at several points in the inflammatory and vascular pathways responsible for diabetic macular oedema.

Suppress inflammatory mediators

They reduce cytokine activity and inhibit prostaglandin and leukotriene synthesis.

Reduce leukostasis

They decrease adhesion-molecule expression and reduce leukocyte adhesion to the retinal vascular endothelium.

Improve the vascular barrier

They stabilise endothelial tight junctions and help restore blood–retinal barrier function.

Reduce vascular permeability

They downregulate VEGF expression and reduce leakage from abnormal retinal vessels.

Corticosteroids are therefore not only anti-inflammatory. Their broader clinical effect is to reduce retinal vascular leakage and macular oedema. [1] [14]

What Is Persistent DME?

Persistent diabetic macular oedema generally means centre-involving retinal thickening that remains despite an adequate course of anti-VEGF treatment . However, there is no single universal clinical definition.

DRCR Protocol I research definition

Persistent DME through 24 weeks

In the DRCR Protocol I secondary analysis, an eye was classified as having persistent DME when both criteria were present:

1.
Central subfield thickness remained 250 µm or more at every completed visit through 24 weeks .
2.
The eye had received at least 4 of the 6 possible protocol-mandated ranibizumab injections .

The 250 µm threshold was based on Stratus OCT-equivalent measurements and should not be applied directly to every modern OCT device. [4]

Chronic persistent DME

Eyes with persistent DME at 24 weeks continued to be classified as having chronic persistent DME until both of the following were achieved on two consecutive subsequent visits:

1.
A central subfield thickness of less than 250 µm.
2.
At least a 10% reduction from the central subfield thickness recorded at the 24-week visit .

The 10% criterion did not define the initial presence of persistent DME. It helped determine when an eye no longer met the study definition of chronic persistent DME.

What did the DRCR analyses show?

31.6% Persistent DME through 24 weeks with aflibercept

65.6% Persistent DME through 24 weeks with bevacizumab

41.5% Persistent DME through 24 weeks with ranibizumab

Persistent retinal thickening was common, but visual acuity could still improve despite incomplete anatomical resolution. [4] [5]

Clinical Update Persistent OCT fluid does not automatically mean that anti-VEGF treatment has failed. Treatment decisions should also consider visual acuity, change from baseline, injection regularity, chronic retinal damage, macular ischaemia and treatment burden.

Where Steroids Fit in DME Treatment

For most eyes with vision-impairing centre-involving diabetic macular oedema, intravitreal anti-VEGF therapy remains the usual first-line treatment. Corticosteroids are considered when the clinical situation favours a different or additional approach.

Anti-VEGF remains first-line in most eyes

Anti-VEGF treatment has the strongest evidence as initial therapy for centre-involving DME associated with visual impairment.

Consider steroids when the response is insufficient

A corticosteroid may be considered when clinically significant oedema persists despite an adequate and regular course of anti-VEGF treatment.

Consider steroids when anti-VEGF is unsuitable

Frequent injections or visits cannot be sustained
Anti-VEGF is unsuitable after individual systemic assessment
A previous corticosteroid produced a useful response
Lens status and ocular circumstances favour steroid therapy

Assess vision, OCT and steroid-related risk together

The decision should integrate visual response, OCT response, lens status, baseline IOP, glaucoma risk, previous steroid response, treatment burden and follow-up reliability.

Corticosteroids should not be introduced simply because the retina remains thick. They are a targeted treatment for an appropriately selected eye and patient. [2] [3]

Selecting a Patient for Steroid Treatment

Steroid selection depends on more than persistent retinal thickening. Lens status, glaucoma risk, previous steroid response, systemic context and the ability to attend follow-up must be considered together.

Features favouring consideration

Pseudophakic eye
Visually significant cataract with cataract surgery already planned
Inadequate response despite an adequate and regular anti-VEGF course
Difficulty sustaining frequent anti-VEGF injections or visits
Previous useful anatomical or visual response to corticosteroid
Previous steroid exposure without a clinically significant IOP rise
Anti-VEGF treatment considered unsuitable after individual risk assessment

Features requiring caution or avoidance

Active or suspected ocular or periocular infection
Active epithelial herpes simplex keratitis
Mycobacterial or fungal ocular infection
Uncontrolled ocular hypertension or advanced glaucoma
Known marked steroid-related IOP response
Inability to return for IOP monitoring
Phakic eye in which cataract progression would substantially affect vision
Hypersensitivity to the drug or implant components

Clinical Update A previous myocardial infarction or cerebrovascular accident is not an automatic class-wide absolute contraindication to intravitreal anti-VEGF therapy. The timing and severity of the event, visual need, systemic risk and available alternatives should be assessed individually. [17]

A phakic eye is not an absolute contraindication to steroid treatment, but the likelihood of cataract progression should be discussed before treatment. [2] [11]

Corticosteroid Options at a Glance

The main intravitreal corticosteroid options differ in their delivery system, duration of action and safety implications.

Treatment	Delivery	Approximate duration	Clinical position	Main practical issue
Triamcinolone acetonide Commonly studied at 1 mg or 4 mg	Intravitreal corticosteroid suspension	Weeks to a few months	Off-label for DME in many regions [6]	Shorter duration, cataract progression and IOP elevation
Dexamethasone implant 0.7 mg	Biodegradable intravitreal implant	Several months	Approved for DME; exact indication varies by region [15]	Recurrence may require retreatment; IOP must be monitored
Fluocinolone acetonide implant 0.19 mg	Non-biodegradable intravitreal insert	Up to approximately 36 months	Long-duration treatment for carefully selected eyes [16]	Prolonged steroid exposure and sustained glaucoma risk

I-vation and Retisert are not included in the main comparison because they are not routine contemporary intravitreal treatments for DME.

Intravitreal Triamcinolone Acetonide

Intravitreal triamcinolone acetonide is a shorter-duration corticosteroid option with established clinical experience in diabetic macular oedema.

Studied doses 1 mg and 4 mg

Duration Weeks to a few months

Regulatory position Off-label for DME in many regions

Preparation supplied Preservative-free sterile ophthalmic suspension, usually 40 mg/mL

Preparing the intravitreal dose

1.
Use a preservative-free, sterile ophthalmic triamcinolone acetonide suspension.
2.
Shake the 40 mg/mL vial vigorously for 10 seconds to obtain a uniform suspension. Inspect the vial for clumping or agglomeration and do not use it if the suspension remains irregular.
3.
Under strict aseptic conditions, withdraw the required volume: 0.025 mL provides 1 mg, while 0.1 mL provides 4 mg.
4.
Use the prepared syringe promptly because triamcinolone particles may settle after withdrawal. [19]

Do not inject a preserved intramuscular or intra-articular preparation directly into the vitreous. When a preservative-free ophthalmic preparation is unavailable, preservative removal and reformulation should be performed by a qualified sterile compounding pharmacy using a validated process. Informal sedimentation, decanting or filtration may produce an unreliable final dose. [20]

What did the major DRCR trials show?

Protocol B

Laser produced better longer-term visual outcomes

The 4 mg triamcinolone group showed an early benefit at four months, but this was not maintained. By two and three years, focal/grid laser produced better mean visual-acuity outcomes than either triamcinolone dose in the population studied. [6]

Protocol I

Pseudophakic eyes revealed the effect of cataract

Ranibizumab-based treatment produced better outcomes overall. However, in eyes that were already pseudophakic, triamcinolone plus prompt laser performed more similarly to the ranibizumab groups, suggesting that cataract progression had obscured part of the steroid-associated visual benefit in phakic eyes. [7]

Exam Pearl In Protocol I, the relative performance of triamcinolone improved in the pseudophakic subgroup, highlighting how steroid-induced cataract can mask visual benefit.

Dexamethasone Intravitreal Implant

The dexamethasone implant provides sustained corticosteroid delivery through a biodegradable intravitreal implant.

Dose 0.7 mg dexamethasone

Delivery system Biodegradable PLGA implant

Clinical effect Typically about 3–4 months [21]

Regulatory position Approved for DME; exact indication varies by region

The implant gradually biodegrades after injection. In clinical practice, its useful anatomical and visual effect commonly lasts approximately 3–4 months, although durability varies between eyes. Recurrence and retreatment should therefore be guided by visual acuity, OCT findings and safety rather than assuming a fixed six-month effect. [21]

Regional product labels differ. Clinical use should follow the locally approved indication and prescribing information. [15]

What did the major trials show?

MEAD

Repeated treatment improved anatomy and vision

In the pooled three-year sham-controlled trials, dexamethasone implants improved retinal thickness and increased the proportion of eyes gaining at least 15 letters. The expected adverse effects were cataract progression and IOP elevation. [8]

Protocol U

Better anatomy did not produce better mean vision

In eyes with persistent DME despite ranibizumab, adding a dexamethasone implant produced a greater reduction in central retinal thickness. It did not provide a significantly greater mean visual-acuity improvement at 24 weeks and caused more IOP-related adverse events. [9]

Exam Pearl A greater reduction in OCT thickness does not necessarily produce a greater visual-acuity gain. Chronic oedema, macular ischaemia, DRIL and outer-retinal damage may limit functional recovery.

Fluocinolone Acetonide Intravitreal Implant

The fluocinolone acetonide implant provides long-duration corticosteroid delivery through a small, non-biodegradable intravitreal insert.

Dose 0.19 mg fluocinolone acetonide

Delivery system Non-biodegradable intravitreal insert

Duration Up to approximately 36 months

Release rate Approximately 0.25 µg per day initially [16]

Because corticosteroid exposure is prolonged, the implant is best used in an eye with a clear need for sustained treatment and acceptable glaucoma risk.

In the United States, the indication specifies previous corticosteroid treatment without a clinically significant rise in intraocular pressure. Regulatory wording varies between regions. [16]

What did the major evidence show?

FAME

Sustained treatment improved anatomy and vision

The FAME trials showed that fluocinolone inserts improved visual and anatomical outcomes over three years. The lower-dose insert provided the more favourable benefit–risk balance and became the basis of the 0.19 mg implant used clinically. [10]

Safety signal

Longer exposure produces longer-duration risk

Cataract development and sustained IOP elevation were common treatment-related adverse effects. Some eyes required glaucoma medication, and a smaller proportion required glaucoma surgery. [10] [11]

Clinical Update The 2026 NEW DAY study evaluated the 0.19 mg implant as baseline DME therapy. It found similar anatomical and visual outcomes with fewer total injections, but more cataract procedures and IOP-related events. The study did not establish fluocinolone as universal first-line treatment. [18]

Clinical Pearl A long-duration implant should be chosen only when the expected reduction in treatment burden justifies prolonged and less reversible steroid exposure.

What About I-vation and Retisert?

These devices are useful for understanding the development of sustained intraocular steroid delivery, but they are not routine contemporary treatments for DME.

I-vation

Investigational triamcinolone delivery system

I-vation was a surgically implanted helical device designed to release triamcinolone over a prolonged period. Its clinical development programme was discontinued, and it is not used as a standard treatment for diabetic macular oedema.

Retisert

Surgically implanted fluocinolone device

Retisert contains 0.59 mg fluocinolone acetonide and is implanted through a pars plana incision. It is indicated for chronic non-infectious posterior-segment uveitis rather than as a standard implant for DME.

For present-day DME management, the principal steroid options are intravitreal triamcinolone, the dexamethasone implant and the 0.19 mg fluocinolone implant.

Safety and Follow-up

Monitoring is part of steroid treatment. Follow-up should detect pressure-related complications, cataract progression, injection-related adverse events and an inadequate functional response.

Risk	What to monitor
Ocular hypertension	Record baseline IOP and repeat IOP measurements after treatment. The timing should reflect the steroid preparation and the patient’s previous pressure response.
Glaucoma progression	Assess the optic nerve and retinal nerve fibre layer. Perform visual-field testing when clinically indicated.
Cataract progression	Monitor lens opacity and determine whether cataract is limiting visual improvement despite anatomical resolution of DME.
Infection or injection-related complication	Urgently reassess new pain, redness, increasing inflammation, discharge or sudden visual decline.
Implant migration	Confirm implant position in susceptible eyes, particularly when posterior-capsule or zonular support is deficient.
Inadequate treatment response	Assess visual acuity and OCT together. Reduced retinal thickness without meaningful visual improvement may reflect chronic structural damage or macular ischaemia.

Can OCT Predict a Better Steroid Response?

Some OCT findings may suggest a more inflammatory or chronic DME phenotype, but none independently determines the choice of steroid treatment.

Swipe horizontally to view the complete table.

OCT finding	High-yield interpretation	Clinical relevance
Subretinal fluid	May indicate a more inflammatory DME phenotype.	Associated with favourable steroid response in some studies.
Hyperreflective foci	May represent inflammatory cells or lipid-related material.	A higher burden may support an inflammatory component.
Chronic intraretinal cysts	Suggest long-standing oedema and possible tissue damage.	Anatomy may improve without equivalent visual recovery.
DRIL	Indicates disorganisation of the inner retinal layers.	Primarily a marker of poorer visual prognosis.
Outer-retinal disruption	Reflects damage to the ellipsoid zone or external limiting membrane.	May limit vision despite reduced retinal thickness.

Interpret these findings with visual acuity, duration of oedema, treatment history and macular perfusion. No single OCT feature is a validated standalone indication for corticosteroid treatment. [12] [13]

Do Not Confuse Hyperreflective foci are not simply degenerated photoreceptors. Their proposed origins include inflammatory cells, lipid-related material and migrating retinal pigment epithelial cells. Choroidal vascularity index remains a research measure.

Practical Treatment Logic

Steroid treatment should follow a clinical sequence rather than a fixed OCT-thickness or injection-number rule.

Step 1

Begin with anti-VEGF in most eyes

Use anti-VEGF as the usual initial treatment for vision-impairing centre-involving DME.

Step 2

Assess the complete response

Visual acuity
OCT change from baseline
Treatment regularity
Macular ischaemia or structural damage
Visit and injection burden

Step 3

Assess steroid suitability

Lens status
Baseline IOP and glaucoma risk
Previous steroid response
Required duration of treatment
Reliability of follow-up

Select the corticosteroid strategy

Triamcinolone Shorter-duration, off-label option.

Dexamethasone implant Biodegradable option with an effect of about 3–4 months.

Fluocinolone implant Long-duration option for carefully selected steroid-tolerant eyes.

Persistent retinal thickening alone is insufficient reason to switch. The decision should reflect both anatomical and functional outcomes, treatment adequacy and steroid-related risk. [2] [4] [9]

Key Takeaways

1.
DME is driven by both VEGF-mediated and inflammatory pathways.
2.
Anti-VEGF remains the usual first-line treatment for most eyes with vision-impairing centre-involving DME.
3.
Persistent OCT thickening does not automatically represent treatment failure; visual response and treatment adequacy must also be assessed.
4.
Steroid selection depends on lens status, glaucoma risk, previous steroid response, required duration and follow-up reliability.
5.
Triamcinolone, dexamethasone and fluocinolone differ mainly in duration, reversibility and steroid-related risk.
6.
Anatomical improvement on OCT does not always translate into an equivalent gain in visual acuity.

References

Numbering corresponds to the inline citations used throughout this companion note.

1.
Noma H, Yasuda K, Shimura M. Involvement of cytokines in the pathogenesis of diabetic macular edema. Int J Mol Sci. 2021;22(7):3427. doi:10.3390/ijms22073427
2.
American Academy of Ophthalmology Preferred Practice Pattern Retina/Vitreous Committee. Diabetic Retinopathy Preferred Practice Pattern®. Ophthalmology. 2025;132(4):P75–P162. doi:10.1016/j.ophtha.2024.12.020
3.
Schmidt-Erfurth U, Garcia-Arumi J, Bandello F, et al. Guidelines for the management of diabetic macular edema by the European Society of Retina Specialists. Ophthalmologica. 2017;237(4):185–222. doi:10.1159/000458539
4.
Bressler SB, Ayala AR, Bressler NM, et al. Persistent macular thickening after ranibizumab treatment for diabetic macular edema with vision impairment. JAMA Ophthalmol. 2016;134(3):278–285. doi:10.1001/jamaophthalmol.2015.5346
5.
Bressler NM, Beaulieu WT, Glassman AR, et al. Persistent macular thickening following intravitreous aflibercept, bevacizumab or ranibizumab for centre-involved diabetic macular edema. JAMA Ophthalmol. 2018;136(3):257–269. doi:10.1001/jamaophthalmol.2017.6565
6.
Diabetic Retinopathy Clinical Research Network. A randomized trial comparing intravitreal triamcinolone acetonide and focal/grid photocoagulation for diabetic macular edema. Ophthalmology. 2008;115(9):1447–1459.e10. doi:10.1016/j.ophtha.2008.06.015
7.
Elman MJ, Aiello LP, Beck RW, et al. Randomized trial evaluating ranibizumab plus prompt or deferred laser or triamcinolone plus prompt laser for diabetic macular edema. Ophthalmology. 2010;117(6):1064–1077.e35. doi:10.1016/j.ophtha.2010.02.031
8.
Boyer DS, Yoon YH, Belfort R Jr, et al. Three-year, randomized, sham-controlled trial of dexamethasone intravitreal implant in patients with diabetic macular edema. Ophthalmology. 2014;121(10):1904–1914. doi:10.1016/j.ophtha.2014.04.024
9.
Maturi RK, Glassman AR, Liu D, et al. Effect of adding dexamethasone to continued ranibizumab treatment in patients with persistent diabetic macular edema. JAMA Ophthalmol. 2018;136(1):29–38. doi:10.1001/jamaophthalmol.2017.4914
10.
Campochiaro PA, Brown DM, Pearson A, et al. Sustained-delivery fluocinolone acetonide vitreous inserts provide benefit for at least three years in patients with diabetic macular edema. Ophthalmology. 2012;119(10):2125–2132. doi:10.1016/j.ophtha.2012.04.030
11.
Goñi FJ, Barton K, Dias JA, et al. Intravitreal corticosteroid implantation in diabetic macular edema: updated European consensus guidance on monitoring and managing intraocular pressure. Ophthalmol Ther. 2022;11(1):15–34. doi:10.1007/s40123-021-00427-1
12.
Vujosevic S, Torresin T, Bini S, et al. Imaging retinal inflammatory biomarkers after intravitreal steroid and anti-VEGF treatment in diabetic macular oedema. Acta Ophthalmol. 2017;95(5):464–471. doi:10.1111/aos.13294
13.
Zur D, Iglicki M, Busch C, et al. OCT biomarkers as functional outcome predictors in diabetic macular edema treated with dexamethasone implant. Ophthalmology. 2018;125(2):267–275. doi:10.1016/j.ophtha.2017.08.031
14.
Chawan-Saad J, Wu M, Wu A, Wu L. Corticosteroids for diabetic macular edema. Taiwan J Ophthalmol. 2019;9(4):233–242. doi:10.4103/tjo.tjo_68_19
15.
AbbVie/Allergan. Ozurdex®—dexamethasone intravitreal implant 0.7 mg. US prescribing information. Current DailyMed label
16.
ANI Pharmaceuticals. Iluvien®—fluocinolone acetonide intravitreal implant 0.19 mg. US prescribing information. Current DailyMed label
17.
Regeneron Pharmaceuticals. Eylea®—aflibercept injection. US prescribing information. Current DailyMed label
18.
Singer MA, Wykoff CC, Riemann CD, et al. Fluocinolone acetonide implant as a baseline therapy for diabetic macular edema: results from the randomized phase 4 NEW DAY study. Ophthalmology. 2026;133(7):837–851. doi:10.1016/j.ophtha.2026.03.019
19.
Harrow Eye, LLC. TRIESENCE®—triamcinolone acetonide injectable suspension 40 mg/mL. US prescribing information. Current DailyMed label
20.
Ober MD, Barza M, Mylevaganam R, et al. Measurement of the actual dose of triamcinolone acetonide delivered after common techniques of preparation for intravitreal injection. Am J Ophthalmol. 2006;142(4):597–600. doi:10.1016/j.ajo.2006.05.022
21.
Canadian Agency for Drugs and Technologies in Health. Clinical Review: Dexamethasone Intravitreal Implant (Ozurdex). CADTH Reimbursement Review. Ottawa: CADTH; 2023. Clinical review