OCT knowledge checker:
Management of DMO

Images provided by Richard Gale, York and Scarborough
Teaching Hospitals, NHS Foundation Trust

Adverse events should be reported.
Reporting forms and information can be found at
https://yellowcard.mhra.gov.uk/ or search MHRA
Yellow Card in Google Play or Apple App Store.
Adverse events should also be reported to Bayer plc.
Tel.: 0118 2063500
Email: pvuk@bayer.com

This material has been developed for use on a desktop computer.

Prescribing information for EYLEA (aflibercept) 2 mg and EYLEA 8 mg can be accessed by clicking the prescribing information link on the hosting website.

DMO, diabetic macular oedema; OCT, optical coherence tomography.
This promotional OCT knowledge checker is organised and funded by Bayer and is intended for UK healthcare professionals only.

The information provided in this presentation is according to the views of the author.

November 2024 | PP-EYL-GB-2282

Disclosures

Fees for:

AbbVie, Alimera Sciences, Allergan, Amgen, Bayer, Biogen, Boehringer Ingelheim, Gilead Sciences, Heidelberg Pharma, Lux Biosciences, Notal Vision, Novartis, Roche, Santen.

Disclaimers

The case studies presented are from real patients and are used with permission.

Triamcinolone acetonide is not licensed for intraocular use.

OCT, optical coherence tomography.

Licensed posology with aflibercept 2 mg in DMO (Section 4.2 of the SmPC)

Aflibercept 2 mg is indicated for adults for the treatment of visual impairment due to diabetic macular oedema (DMO).

The recommended dose for aflibercept is 2 mg, equivalent to 0.05 mL.

Aflibercept treatment is initiated with one injection per month for five consecutive doses, followed by one injection every two months. There is no requirement for monitoring between injections.

Based on the physician's judgement of visual and/or anatomic outcomes, the treatment interval may be extended, such as with a treat-and-extend dosing regimen, where the treatment intervals are usually increased by 2-week increments to maintain stable visual and/or anatomic outcomes. There are limited data for treatment intervals longer than 4 months. If visual and/or anatomic outcomes deteriorate, the treatment interval should be shortened accordingly.

Treatment intervals shorter than 4 weeks have not been studied (see section 5.1 of the SmPC).

The schedule for monitoring should be determined by the treating physician.

If visual and anatomic outcomes indicate that the patient is not benefiting from continued treatment, aflibercept should be discontinued.

DMO, diabetic macular oedema; SmPC, Summary of Product Characteristics.
Bayer plc. Aflibercept 2 mg – summary of product characteristics.

Licensed posology with aflibercept 8 mg in DMO (Section 4.2 of the SmPC)

Aflibercept 114.3 mg/mL is indicated in adults for the treatment of neovascular (wet) age-related macular degeneration (nAMD) and visual impairment due to diabetic macular oedema (DMO).

The recommended dose is 8 mg aflibercept, equivalent to 0.07 mL solution. The 8 mg dose requires use of the aflibercept 114.3 mg/mL solution for injection.

Aflibercept treatment is initiated with 1 injection per month for 3 consecutive doses. Injection intervals may then be extended up to every 4 months based on the physician's judgement of visual and/or anatomic outcomes. Subsequently, the treatment intervals may be further extended up to 5 months, such as with a treat-and-extend dosing regimen, while maintaining stable visual and/or anatomic outcomes (see section 5.1 [of the SmPC]).

If visual and/or anatomic outcomes deteriorate, the treatment interval should be shortened accordingly based on the physician's discretion. The shortest interval between 2 injections is 2 months in the maintenance phase.

Aflibercept at monthly doses of 8 mg has not been studied for more than 3 consecutive doses.

The frequency of monitoring visits should be based on the patient's status and at the physician's discretion.

For events in which treatment should be withheld see section 4.4 [of the SmPC].

DMO, diabetic macular oedema; SmPC, Summary of Product Characteristics.
Bayer plc. Aflibercept 8 mg – summary of product characteristics.

How can DMO be managed?

Click on an option to learn more.

DMO, diabetic macular oedema; VEGF, vascular endothelial growth factor.

Control of systemic risk factors in DMO

Progression of DMO is related to a variety of risk factors, particularly those relating to the control of diabetes mellitus¹

Control of blood glucose, blood pressure and cholesterol, as well as smoking cessation, may improve outcomes in patients with DMO¹

A 2023 meta-analysis of 106,819 patients across 93 studies reported an association between treatment with GLP-1 receptor agonists and both early-stage diabetic retinopathy and early-stage ocular AEs²

Additional ophthalmic monitoring should be considered in patients undergoing treatment with a GLP-1 receptor agonist²

AE, adverse event; DMO, diabetic macular oedema; GLP, glucagon-like peptide. 1. Amoaku WM et al. Eye 2020; 34: 1–51. 2. Kapoor I et al. Surv Ophthalmol 2023; 68: 1071–1083.

Anti-VEGF therapy for DMO

Example OCT map from an eye with a CRT >400 µm

NICE recommends that intravitreal anti-VEGF therapies such as aflibercept 2 mg, aflibercept 8 mg, faricimab and ranibizumab should be offered for eyes with centre-involving, vision-affecting DMO with a CRT ≥400 µm at the start of treatment^1–3

NICE recommendations published in August 2024 state that anti-VEGF therapy may also be considered for the treatment of eyes with centre-involving, vision-affecting DMO with a CRT <400 µm⁴

Image courtesy of author. CRT, central retinal thickness; DMO, diabetic macular oedema; NICE, National Institute for Health and Care Excellence; OCT, optical coherence tomography; VEGF, vascular endothelial growth factor. 1. NICE. TA346: Guidance. Available at: https://www.nice.org.uk/guidance/ta346/chapter/1-Guidance. Accessed November 2024. 2. NICE. TA 799: Recommendations. Available at: https://www.nice.org.uk/guidance/TA799/chapter/1-Recommendations. Accessed November 2024. 3. NICE. TA274: Guidance. Available at: https://www.nice.org.uk/guidance/ta274/chapter/1-Guidance. Accessed November 2024. 4. NICE. Diabetic retinopathy: management and monitoring. Available at: https://www.nice.org.uk/guidance/ng242/chapter/Recommendations. Accessed November 2024.

Initiation of anti-VEGF treatment for visual impairment due to DMO

Anti-VEGF agent	Initiation of treatment for visual impairment due to DMO
Aflibercept 2 mg	1 injection per month for 5 consecutive doses, followed by one injection every two months¹
Aflibercept 8 mg	1 injection per month for 3 consecutive doses²
Faricimab	1 injection per month for 4 consecutive doses³
Ranibizumab	1 injection per month until maximum visual acuity is achieved and/or there are no signs of disease activity i.e., no change in visual acuity and in other signs and symptoms of the disease under continued treatment. Three or more initial monthly injections may be needed⁴

DMO, diabetic macular oedema; VEGF, vascular endothelial growth factor. 1. Bayer plc. Aflibercept 2 mg – summary of product characteristics. 2. Bayer plc. Aflibercept 8 mg – summary of product characteristics. 3. Roche Products Ltd. Faricimab – summary of product characteristics. 4. Novartis Pharmaceuticals UK Ltd. Ranibizumab – summary of product characteristics.

Anti-VEGF treatment for DMO: Case study 1

A 54-year-old male patient with visual impairment due to DMO received initial treatment with 5x aflibercept 2 mg q4 in his right eye

After the fifth injection, CRT had decreased from baseline and the interval between aflibercept 2 mg injections was extended to eight weeks

CRT, central retinal thickness; DMO, diabetic macular oedema; q4, every 4 weeks; VEGF, vascular endothelial growth factor. Images and information courtesy of author.

Anti-VEGF treatment for DMO: Case study 2

A 61-year-old male patient with visual impairment due to DMO received initial treatment with 3x aflibercept 8 mg q4 in his right eye

After the third injection, CRT had decreased from baseline

To learn more about this case study, view the poster of this case available on the Retinal Pioneers Hub

CRT, central retinal thickness; DMO, diabetic macular oedema; q4, every 4 weeks; VEGF, vascular endothelial growth factor. Images and information courtesy of author.

Anti-VEGF treatment regimens for visual impairment due to DMO

After the loading phase, a number of treatment regimens are sometimes used with different anti-VEGF agents, including:

Fixed dosing

Treat-and-extend (T&E)

Pro re nata (PRN; as needed)

There is a growing body of evidence to support the use of T&E regimens in the maintenance phase of anti-VEGF treatment for visual impairment due to DMO

T&E regimens offer the potential for a reduced treatment and/or appointment burden relative to PRN or fixed dosing at short intervals

VEGF, vascular endothelial growth factor. Lim SY et al. Graefs Arch Clin Exp Ophthalmol 2023; 261: 303315.

Anti-VEGF treatment regimens during the maintenance phase for visual impairment due to DMO (1)

Anti-VEGF agent	Treatment during the maintenance phase for visual impairment due to DMO
Aflibercept 2 mg	Treatment is extended to one injection every 2 months after the initial 5 monthly loading doses. Based on the physician's judgement of visual and/or anatomic outcomes, the treatment interval may be maintained at 2 months or individualized, such as with a T&E dosing regimen, where the treatment intervals are usually increased by 2-week increments to maintain stable visual and/or anatomic outcomes. There are limited data for treatment intervals longer than 4 months. If visual and/or anatomic outcomes deteriorate, the treatment interval should be shortened accordingly. Treatment intervals shorter than 4 weeks have not been studied.¹
Aflibercept 8 mg	Treatment can be extended up to every 4 months after the initial 3 monthly loading doses. Subsequently, the treatment intervals may be further extended up to 5 months, such as with a T&E dosing regimen, while maintaining stable visual and/or anatomic outcomes.²

Anti-VEGF agent

Treatment during the maintenance phase for visual impairment due to DMO

Aflibercept 2 mg

Treatment is extended to one injection every 2 months after the initial 5 monthly loading doses. Based on the physician's judgement of visual and/or anatomic outcomes, the treatment interval may be maintained at 2 months or individualized, such as with a T&E dosing regimen, where the treatment intervals are usually increased by 2-week increments to maintain stable visual and/or anatomic outcomes. There are limited data for treatment intervals longer than 4 months. If visual and/or anatomic outcomes deteriorate, the treatment interval should be shortened accordingly. Treatment intervals shorter than 4 weeks have not been studied.¹

Aflibercept 8 mg

Treatment can be extended up to every 4 months after the initial 3 monthly loading doses. Subsequently, the treatment intervals may be further extended up to 5 months, such as with a T&E dosing regimen, while maintaining stable visual and/or anatomic outcomes.²

DMO, diabetic macular oedema; VEGF, vascular endothelial growth factor. 1. Bayer plc. Aflibercept 2 mg – summary of product characteristics. 2. Bayer plc. Aflibercept 8 mg – summary of product characteristics.

Anti-VEGF treatment regimens during the maintenance phase for visual impairment due to DMO (2)

Anti-VEGF agent	Treatment during the maintenance phase for visual impairment due to DMO
Faricimab	Treatment can be individualised after the loading phase, using a T&E approach, following an assessment of the individual patient's anatomic and visual outcomes. The dosing interval may be extended from every 4 to every 16 weeks, with extensions in increments of up to 4 weeks, based on the physician's judgement of the individual patient's anatomic and/or visual outcomes. If anatomic and/or visual outcomes change, the treatment interval should be adjusted accordingly, and interval reductions of up to 8 weeks may be implemented if deemed necessary.¹
Ranibizumab	Treatment intervals and associated monitoring intervals should be determined by the physician and should be based on disease activity, as assessed by visual acuity and/or anatomical parameters. Monitoring for disease activity may include clinical examination, functional testing or imaging techniques (e.g. optical coherence tomography or fluorescein angiography). If patients are being treated according to a T&E regimen, once maximum visual acuity is achieved and/or there are no signs of disease activity, the treatment intervals can be extended stepwise until signs of disease activity or visual impairment recur. The treatment interval should be extended by up to one month at a time for DMO.²

Anti-VEGF agent

Treatment during the maintenance phase for visual impairment due to DMO

Faricimab

Treatment can be individualised after the loading phase, using a T&E approach, following an assessment of the individual patient's anatomic and visual outcomes. The dosing interval may be extended from every 4 to every 16 weeks, with extensions in increments of up to 4 weeks, based on the physician's judgement of the individual patient's anatomic and/or visual outcomes. If anatomic and/or visual outcomes change, the treatment interval should be adjusted accordingly, and interval reductions of up to 8 weeks may be implemented if deemed necessary.¹

Ranibizumab

Treatment intervals and associated monitoring intervals should be determined by the physician and should be based on disease activity, as assessed by visual acuity and/or anatomical parameters. Monitoring for disease activity may include clinical examination, functional testing or imaging techniques (e.g. optical coherence tomography or fluorescein angiography). If patients are being treated according to a T&E regimen, once maximum visual acuity is achieved and/or there are no signs of disease activity, the treatment intervals can be extended stepwise until signs of disease activity or visual impairment recur. The treatment interval should be extended by up to one month at a time for DMO.²

DMO, diabetic macular oedema; VEGF, vascular endothelial growth factor. 1. Roche Products Ltd. Faricimab – summary of product characteristics. 2. Novartis Pharmaceuticals UK Ltd. Ranibizumab – summary of product characteristics.

How do we define stability to help us with retreatment criteria?

OCT map shows a change of 200 µm, which is >10% of the baseline value and is considered to be a clinically significant change⁵

The mean diurnal variation in CRT is reported to be <10%^1,2

Once maximum drying is reached for a patient, only changes in CRT ≥10% from this maximum should be used to inform decisions regarding treatment intervals^3–5

Consequently, a change <10% is often used to define stability⁵

CRT, central retinal thickness; DMO, diabetic macular oedema; q4, every 4 weeks; VEGF, vascular endothelial growth factor. 1. Polito A et al. Retina 2006; 26 (1): 14–20. 2. DRCR.net. Arch Ophthalmol 2006; 124 (12): 1701–1707. 3. DRCR.net. Ophthalmology 2010; 117: 1064–1077. 4. RCOphth. Diabetic Retinopathy Guidelines, December 2012. Available at: https://www.rcophth.ac.uk/resources-listing/diabetic-retinopathy-guidelines/. Accessed November 2024. 5. Information courtesy of author.

Steroid-based treatment for DMO

Steroid-based treatments include dexamethasone and fluocinolone acetonide intravitreal implants

NICE recommends that:

Dexamethasone intravitreal implant is an option for treating visual impairment caused by DMO in adults only if their condition has not responded well enough to, or if they cannot have, non-corticosteroid therapy¹

Fluocinolone acetonide implants is an option for treating visual impairment caused by chronic DMO that has not responded well enough to available treatments in adults (including dexamethasone implants)²

Diabetic Retinopathy Clinical Research Network studies suggest that off-label use of sub-Tenon triamcinolone acetonide is unlikely to be of substantial benefit for patients with mild DMO³

1. NICE. TA824: Recommendations. Available at: https://www.nice.org.uk/guidance/ta824/chapter/1-Recommendations. Accessed November 2024. 2. NICE. TA953: Recommendations. Available at: https://www.nice.org.uk/guidance/ta953/chapter/1-Recommendations. Accessed November 2024. 3..DRCR.net. Ophthalmology 2007; 114: 1190–1196.

Laser photocoagulation for DMO

Adapted from ETDRS, 1985.

The use of laser photocoagulation in clinical practice was established following the Early Treatment Diabetic Retinopathy Study (ETDRS)^1,2

Among eyes with CSMO, eyes assigned to immediate focal laser photocoagulation were approximately half as likely to lose ≥15 ETDRS letters from baseline at Year 3 as eyes receiving deferred laser photocoagulation (eye losing ≥15 ETDRS letters: immediate focal laser, n=32/268; deferred treatment, n=126/526)¹

CSMO was defined as one or more of the following:¹

An area or areas of retinal thickening one disc area in size, at least part of which is within one disc diameter of the fovea

Hard exudates at or within 500 μm of the fovea if associated with adjacent retinal thickening

Retinal thickening at or within 500 μm of the fovea

DMO, diabetic macular oedema; CSMO, clinically significant macular oedema; NPDR, non-proliferative diabetic retinopathy. 1. ETDRS Research Group. JAMA 1985; 103: 1796–1806. 2. RCOphth. Diabetic Retinopathy Guidelines, December 2012. Available at: https://www.rcophth.ac.uk/resources-listing/diabetic-retinopathy-guidelines/. Accessed November 2024.

Summary: Management of DMO^1,2

The interplay between the treatment and management of diabetes and DMO is complex; as such, a variety of treatment options can be used to manage DMO according to the needs of the individual patient, including the following:

Control of systemic risk factors

Anti-VEGF therapy

Steroid-based treatments

Laser photocoagulation

DMO, diabetic macular oedema; OCT, optical coherence tomography; VEGF, vascular endothelial growth factor. 1. Information courtesy of author. 2. RCOphth. Diabetic Retinopathy Guidelines, December 2012. Available at: https://www.rcophth.ac.uk/resources-listing/diabetic-retinopathy-guidelines/. Accessed November 2024.

Thank you for completing this OCT knowledge checker