Retinal Disease Management’s Future: Global Retinal Network Program 2024

The two-day August conference, held in Sydney, delved into exploring clinical trials and real-world patient cases with the higher dose formulation of Eylea (aflibercept), designed to address unmet clinical needs and offer sustained disease control and reduce the treatment burden for patients. The conference encapsulated the clinical rationale for the higher dose, outlining the differences between the existing 2 mg and new 8 mg formulations and their impact on patient outcomes.

Attended by over 200 eye health professionals from all over the Asia Pacific region, the event featured a strong line up of both local and international experts including Dr Peter Kaiser (United States), Professors Marion Munk (Switzerland), Adrian Fung (Sydney), Varun Chaudhary (Canada), Andrew Chang AM (Sydney), Dr Amy Cohn (Melbourne), Associate Professor Voraporn Chaikitmongkol (Thailand), and Drs Kelvin Teo and Tien Yin Wong (both Singapore).

Evolution of Retinal Disease Management

Prof Munk kick-started the conference with an insightful reflection on the evolution of retinal disease management, tracing the history of anti-vascular endothelial growth factor (anti-VEGF). She highlighted key milestones in the approval of Eylea for various retinal conditions in Australia:

• 2011: Eylea 2 mg was first approved for nAMD,

• 2012: Approval was extended to central retinal vein occlusion (CRVO),

• 2014: Eylea 2 mg was approved for DMO,

• 2014–2015: Further approvals followed for branch retinal vein occlusion (BRVO) and myopic choroidal neovascularisation (mCNV), and

• 2019: Eylea 2 mg was first approved for pre-filled syringe (PFS).

Looking ahead, Prof Munk highlighted the potential for longer-lasting disease control with the introduction of aflibercept 8 mg, sparking anticipation for the future of retinal treatment, particularly with the global prevalence and impact of nAMD and DMO expected to rise. She said that AMD was the main cause of severe visual impairment and irreversible blindness in the industrialised world, and emphasised the necessity for solutions to address unmet needs with current intravitreal therapies.

Sustained Disease Control

Dr Kaiser, from the Cole Eye Institute Cleveland Clinic in the United States, outlined the rationale for increasing the molar dose of aflibercept. The two differences for Eylea 8 mg revolve around the slower ocular clearance and higher molecular dose. Improving the molecular properties of binding affinity, potency, ocular adherence, and molecular targets can improve how well an agent can suppress VEGF.

In comparison to other licenced intravitreal (IV) therapies, the aflibercept molecule has the highest reported potency, binding affinity, and number of molecular targets, deeming it to be suited for durable suppression of VEGF, Dr Kaiser explained. Slow ocular clearance enables the drug to last longer, hence these longer acting agents may be able to increase VEGF suppression time, extending the time between injections compared with current treatment options.

Trial Outcomes

Dr Kaiser presented trial outcomes in patients with nAMD from the PULSAR study, which demonstrated that the 8 mg aflibercept molecule remains the same as 2 mg, with the additional benefit of a four-fold higher molar dose and reportedly, 34% slower ocular clearance compared to aflibercept 2 mg.1,2

Prof Chaudhary presented trial outcomes from the PHOTON study in patients with DMO which reported aflibercept 8 mg was able to demonstrate efficacy and safety with extended dosing intervals in patients with DMO.3

Compared with 2 mg, aflibercept 8 mg offers the potential for longer-lasting control of disease activity through sustained disease control for all patient types (nAMD and DMO). Pooled data from the CANDELA,4 PULSAR,1 and PHOTON3 studies highlight the comparable safety profile of aflibercept 2 mg and 8 mg. Summarising the three studies, Prof Chaudhary said there were no cases of occlusive retinitis, endophthalmitis or retinal vasculitis with aflibercept 8 mg.^1,3,4

Pre-injection intraocular pressure (IOP) values were also similar to baseline values at all time points during the duration of the trial, Prof Chaudhary explained.

Compared with 2 mg, aflibercept 8 mg offers the potential for longer-lasting control of disease activity through sustained disease control

From Trials to the Clinic

Dr Kaiser and Prof Munk also shared their perspectives and experiences managing patients with aflibercept in real-world settings. With the introduction of more durable agents, Dr Kaiser believes that patient adherence will be less of an issue. He recommended that patients and their caregivers should receive reminders via email and SMS one week and one day before their appointments, which helps improve compliance.

Prof Munk noted that the 8 mg dose is more viscous than the 2 mg, which may cause more bubbles during injection, and recommended patients be informed of this. For those concerned about IOP increase, techniques such as ocular massage with a q-tip pressure and injecting slowly and gently are recommended to mitigate issues like browning and blackening. For patients already on anti-VEGF therapy, treating ophthalmologists should refer to the product information regarding loading doses, the conference heard. When extending treatment intervals for nAMD patients on aflibercept 8 mg, a conservative approach with two-week increments is common, although based on the ALTAIR study, four week extensions are also considered safe.5 They recommended extended intervals be considered to decrease treatment burden in patients with DMO, as these patients are typically younger, more economically stable, and have multiple comorbidities.

Advances in Screening

Professor Peter van Wijngaarden, Managing Director of The Florey and Professor of Ophthalmology at the University of Melbourne, shared alarming statistics showing 1.5 million people in Australia are diagnosed with diabetes however approximately 50% do not get regular eye checks, resulting in avoidable vision loss and blindness in patients with diabetic retinopathy. Prof van Wijngaarden emphasised the importance of systemisation when it comes to diabetic retinopathy screening. As the co-founder and Clinical Director of KeepSight, he spoke about the value of the reminder system for patients with diabetes. KeepSight, launched in 2019, has already had a major impact with 500,000 active registrants and has proven to increase the return rate for diabetic retinopathy screening by 20%, Prof van Wijngaarden said.

Assoc Prof Teo, from Singapore’s Advanced Eye Clinic and Surgery then shared insights on artificial intelligence (AI)-related digital transformation initiatives in Singapore. Through the Singapore Integrated Diabetic Retinopathy Program (SIDRP), patients’ fundus images are sent to a reading centre where graders analyse these images and provide a report in about an hour. However, as the diabetic population grows, the workload has increased, putting significant pressure on manual graders. To address this challenge, the Selena+ deep learning program was introduced, which uses AI to screen diabetic retinopathy pictures. It is able to detect and grade diabetic retinopathy as well as pick up other diseases like glaucoma, AMD, and optic neuritis. Assoc Prof Teo outlined some of the challenges – including lack of trust and implementation challenges. He said the program had not resulted in financial savings, due to the cost of setting up the infrastructure, data hubs, and networking systems.

This session was followed with a provocative debate on the controversial topic of whether AI will replace the need for clinicians in the future. Although strong points were raised on both sides, all members were able to agree that collaboration between AI and medicine has the potential for promising advances in improving medical diagnosis; however, it is unable to replace the training and expertise of health professionals.

If we can reduce their disease activity with less injections over time, I think that’s going to be a big effort

Embracing Change

The two-day conference concluded with a final session on how eye care professionals can embrace and adapt to aflibercept 8 mg.

The speaker panel agreed that they felt confident commencing treatment with aflibercept 8 mg and switching from other anti-VEGF agents. Internationally renowned macular disease expert, Professor Paul Mitchell (Sydney) noted that longer injecting intervals will be particularly beneficial for patients who are balancing work and other responsibilities.

“If we can reduce their disease activity with less injections over time, I think that’s going to be a big effort,” Prof Mitchell said. He told the audience that he has already started a few of his patients on aflibercept 8 mg, and is looking forward to using it routinely.

Dr Kaiser reassured the audience that he sees no reason not to use the new drug on treatment naive or a previously treated patient, as no safety issues have been associated with aflibercept 8 mg.

He also mentioned that in his opinion, four-week extension intervals in DMO are very reasonable, however for AMD, it is better to be safe and only extend by two weeks as any damage done can be permanent.

The conference was hosted by Bayer, manufacturer of Eylea.

Carol Nguyen and Jennifer Doeur are in their final year of a Bachelor of Vision Science/Masters of Clinical Optometry degree at University of New South Wales. Ms Nguyen is currently working as an optical dispenser at 1001 Optometry in Bondi Junction, and has special interests in specialty contact lenses, myopia control, and the management of dry eye disease. Ms Doeur is currently working as an optical dispenser at HCF Eyecare. She is particularly interested in contact lenses and ocular pathology.

References

1. Lanzetta P, Korobelnik JF, Wong TY et al; PULSAR Investigators. Intravitreal aflibercept 8 mg in neovascular age-related macular degeneration (PULSAR): 48-week results from a randomised, double-masked, non-inferiority, phase 3 trial. Lancet. 2024 Mar 23;403(10432):1141-1152. doi: 10.1016/S0140-6736(24)00063-1.
2. European Medicines Agency, Assessment Report: Eylea (EMA/538733/2023) 9 November 2023, available at: ema.europa.eu/en/documents/variation-report/eylea-h-c-2392-x-84-g-epar-assessment-report-variation_en.pdf. Accessed Sept 2024.
3. Brown DM, Boyer DS, Sivaprasad S, et al; PHOTON Investigators. Intravitreal aflibercept 8 mg in diabetic macular oedema (PHOTON): 48-week results from a randomised, double-masked, non-inferiority, phase 2/3 trial. Lancet. 2024 Mar 23;403(10432):1153-1163. doi: 10.1016/S0140-6736(23)02577-1.
4. Wykoff CC, Brown DM, Vitti R, et al; CANDELA Study Investigators. Effect of high-dose intravitreal aflibercept, 8 mg, in patients with neovascular age-related macular degeneration: The Phase 2 CANDELA randomized clinical trial. JAMA Ophthalmol. 2023 Sep 1;141(9):834-842. doi: 10.1001/jamaophthalmol.2023.2421.
5. Okada AA, Takahashi K, Sasaki K, et al. ALTAIR Study Investigators. Efficacy and safety of intravitreal aflibercept treat-and-extend regimens in the ALTAIR study: 96-week outcomes in the polypoidal choroidal vasculopathy subgroup. Adv Ther. 2022 Jun;39(6):2984-2998. doi: 10.1007/s12325-022-02162-w.