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Adopting a multi-pronged approach

Technological breakthroughs provide a range of options for the treatment of age-related macular degeneration

Priscilla Lynch

Posted: Thursday, April 1, 2021

A multi-pronged approach to better prevent, diagnose, monitor and treat age-related macular degeneration (AMD) using the latest exciting knowledge and technology breakthroughs is on the way, and will bring better outcomes for patients, heard the dedicated AMD session held during the 2020 virtual EURETINA Congress.

Caroline Klaver MD, the Netherlands, discussed new insights in AMD derived from the European Union-funded Eye-Risk research consortium, which, using a systems medicine approach, has identified many new risk factors, molecular mechanisms and therapeutic approaches for AMD.

The creation of the Eye-Risk database (from 20 existing longitudinal epidemiological cohorts and biobanks [1991-2015]) was the first task of the consortium, she explained: “We now have extensive data on 53,000 subjects with data on phenotype, genotype, environmental risk factors and blood biomarkers.” The next task for Eye-Risk was to develop an AMD genotype pipeline. “The pipeline [assay] allows genotyping of virtually all associated AMD SNPs and genotypes several AMD genes entirely for the rare variants, and genotypes genes of macular dystrophies that mimic AMD to rule out misclassification,” she said.

The entire Eye-Risk cohort has now been genotyped with a summary of all AMD risk variants, creating the ‘genetic risk score’. “It shows that late AMD has higher genetic risk scores overall than intermediate and non-AMD but there is considerable overlap.”

Eye-Risk has also categorised all the genetic risks into pathways. “We also saw that most AMD patients carry genetic risk variants in at least three pathways.”Further Eye-Risk research has identified numerous AMD metabolic biomarkers from blood; especially lipids, amino acids and citrate. “The next steps are to use genetics and genomics and the lessons learned from systems biology to guide the development of personalised interventions,” Prof Klaver stated.

Discussing approaches to slow progression of intermediate AMD, Robyn Guymer MD, Australia, highlighted the potential use of laser intervention. She noted that while trials of prophylactic thermal laser in the 1990s were shelved due to fears around increased risk of choroidal neovascularisation (CNV), and a 2015 Cochrane review found that despite evidence of resolution of drusen there was no difference in rates of advanced AMD from this approach, there is now renewed interest in using new nonthermal continuous wave laser modalities.

The aim is to reduce the thermal damage and potential inflammatory stimulus for CNV but harness any drusen-resolving effects.

“So now the short duration pulsed lasers (micropulse and nanosecond lasers) have been developed to see if they can selectively target the RPE [retinal pigment epithelium] and not cause any collateral damage to neuro retina,” Prof Guymer said, outlining her own subthreshold nanosecond study experiences.

While her randomised controlled study (LEAD) did not find any overall significant difference in progression to late AMD in those receiving laser versus sham treatment; upon further investigation it found a significant treatment effect modification according to the presence of reticular pseudodrusen (RPD) at baseline. “So potentially there is a benefit for those without coexistent RPD. I think the results are intriguing and deserve ongoing investigation.”

Concluding, Prof Guymer stressed that there remains a dearth of randomised controlled trials in intermediate AMD, “but I think the new ways of using multimodal imaging to define the earlier stages of AMD should lead to an increase in clinical trial activity in these earlier stages of AMD”.

Adnan Tufail MD, UK, discussed the impact of artificial intelligence (AI)-based biomarker detection in OCT scans of AMD patients. He said that AI biomarker detection is rapidly evolving and will in the future inform treatment choice and assessment.

Deep learning algorithms can now be used to identify AMD biomarkers of the biological process, such as retinal pigment epithelium (RPE)/Bruch’s membrane thickness and choroidal thickness, as well as the pathogenic process in neovascular AMD. “The challenge going forward is identifying which patients progress from intermediate to late atrophic AMD,” Prof Tufail said, noting that the detection of features such as reticular pseudodrusen will be important in this regard.

TREATMENT ADHERENCE
Looking at the present, in patients who currently have AMD, Anat Loewenstein MD, Israel, discussed efforts to improve adherence and outcomes in AMD therapy using home monitoring, noting that the COVID-19 pandemic has highlighted the need for more remote patient monitoring.

She showed how information generated by tele-connected self-operated OCT in patients’ homes has the potential to support current retinal disease management and any future evolutions that may occur in monitoring patterns, drug selection and dosing, and patient outcomes. The benefits of home OCT for personalising eAMD management include catching ‘wet’ days as soon as they occur, thus avoiding undertreatment and improving visual acuity outcomes as well as reducing costs and treatment burden, and improving patient satisfaction, with very positive trial data to date, Prof Lowenstein outlined.

LONGER-ACTING TREATMENTS
Also speaking during this session was Jordi Mones MD, Spain, who addressed novel therapeutic approaches for neovascular AMD, highlighting the latest promising intravitreal drugs, intraocular devices and gene therapies in various clinical trials, which will bring longer duration outcome efficacy for AMD patients.

Finally, Carl Regillo MD, USA, also discussed long-acting drug delivery in nAMD, specifically the ARCHWAY phase III results, which found that 98.4% of wet AMD patients using an investigational port delivery system implant were able to go six months without needing additional treatment and achieved visual outcomes equivalent to patients receiving monthly ranibizumab injections.


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