Emerging Therapies in Nonexudative Age-Related Macular Degeneration in 2020

Samanta, Anindya; Aziz, Aamir; Jhingan, Mahima; Singh, Sumit Randhir; Khanani, Arshad M.; Chhablani, Jay

doi:10.1097/apo.0000000000000355

Cited by 17 publications

(20 citation statements)

References 27 publications

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“…Our study findings indicate that GA progression was lower in both the treated (0.5 mm 2 ) and fellow eyes (0.62 mm 2 ) over the study period, suggesting a possible treatment effect of FCA. Both the GATHER one and Filly studies have reported a 20%–30% reduction the rate of GA progression over 12 months, 23 our findings report a similar rate of 19.9%.…”

Section: Discussionsupporting

confidence: 82%

Phase 1B study of the safety and tolerability of the mineralocorticoid fludrocortisone acetate in patients with geographical atrophy

Hong¹,

Chang

Maddess

et al. 2022

BMJ Open Ophth

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ObjectiveTo evaluate the safety and tolerability of a mineralocorticoid, in a single-dose intravitreal (IVT) injection of 1 mg/0.1 mL and 2 mg/0.1 mL fludrocortisone acetate (FCA) in subjects with geographical atrophy (GA) secondary to age-related macular degeneration.Methods and AnalysisThis phase 1b study was a two-part dose-escalation prospective study. Part 1 involved a single participant treated with 1 mg/0.1 mL and monitored up to 28 days before being reviewed by a safety review committee. Two subsequent participants were then dosed with the same dose. Part 2 involved a single participant dosed with 2 mg/0.1 mL and monitored up to 28 days when a further five participants were dosed. All participants were followed up for 6 months after baseline.A full ophthalmic assessment was performed at study visits which included GA area, best-corrected visual acuity (BCVA), low-luminance BCVA (LL-BCVA) and intraocular pressure (IOP). Adverse events (AEs) were reported from the first dose of FCA until the end-of-study visit.ResultsThere were no serious AEs (ocular or systemic) observed with IVT FCA at either 1 mg/0.1 mL or 2 mg/0.1 mL among nine participants. There was no evidence of increased IOP or cataract development.Neither BCVA or LL-BCVA changed significantly in the study-eye over the follow-up period (p=0.28 and 0.38, respectively). Mean GA area increased in the study (0.5 mm2, p=0.003) and fellow-eyes (0.62 mm2, p=0.02) over 6 months. Differences between eyes were not significant (p=0.64), and at the lower end of population norms.ConclusionIVT FCA is clinically safe and well tolerated and did not increase IOP.

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Section: Discussionsupporting

confidence: 82%

Phase 1B study of the safety and tolerability of the mineralocorticoid fludrocortisone acetate in patients with geographical atrophy

Hong¹,

Chang

Maddess

et al. 2022

BMJ Open Ophth

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“…As an example, results from the current study suggest a patient harboring the CFH Y402H genotype may benefit from therapies aimed at improving retinal mitochondrial function potentially by targeting the intracellular complement pathway. This idea is particularly relevant considering the number of therapeutics currently in clinical trials for AMD that disrupt the complement cascade by either inhibiting complement components (i.e., C5, C3) or increasing molecules that inhibit the complement cascade (CFH, CD59) [61].…”

Section: Discussionmentioning

confidence: 99%

Impaired Mitochondrial Function in iPSC-Retinal Pigment Epithelium with the Complement Factor H Polymorphism for Age-Related Macular Degeneration

Ebeling

Geng

Kapphahn

et al. 2021

Cells

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Age-related macular degeneration (AMD), the leading cause of vision loss in the elderly, is characterized by loss of the retinal pigment epithelium (RPE). While the disease mechanism remains unclear, prior studies have linked AMD with RPE mitochondrial defects and genetic polymorphisms in the complement pathway. This study used RPE generated from induced pluripotent stem cells (iPSC-RPE), which were derived from human donors with or without AMD and genotyped for the complement factor H (CFH) AMD high-risk allele (rs1061170, Y402H) to investigate whether donor disease state or genotype had a detrimental effect on mitochondrial function and inflammation. Results show that cells derived from donors with AMD display decreased mitochondrial function under conditions of stress and elevated expression of inflammatory markers compared to iPSC-RPE from individuals without AMD. A more pronounced reduction in mitochondrial function and increased inflammatory markers was observed in CFH high-risk cells, irrespective of disease state. These results provide evidence for a previously unrecognized link between CFH and mitochondrial function that could contribute to RPE loss in AMD patients harboring the CFH high-risk genotype.

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Section: Discussionmentioning

confidence: 99%

“…Although patients with advanced stages (geographic atrophy or exudative AMD) have been included as a subset, future work may investigate the potential for PBT to serve as an adjunctive treatment in exudative AMD and clarify the potential role it may play in a dedicated GA subset without center involvement. 40,42,43,50 Available studies suggest PBT is best suited to AREDS stages 2-4 AMD, where it might alter complement deposition, attenuate oxidative damage, and enhance mitochondrial function. As with DME, the patient subset is narrow, shared in study design limitations, and high-level evidence remains wanting.…”

Section: Age-related Macular Degeneration: Clinical Applicationsmentioning

confidence: 99%

Photobiomodulation Therapy for Age-Related Macular Degeneration and Diabetic Retinopathy: A Review

Muste¹,

Russell²,

Singh³

2021

OPTH

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Purpose Photobiomodulation therapy (PBT) has emerged as a possible treatment for age-related macular degeneration (AMD) and diabetic retinopathy (DR). This review seeks to summarize the application of PBT in AMD and DR. Methods The National Clinical Trial (NCT) database and PubMed were queried using a literature search strategy and reviewed by the authors. Results Fourteen studies examining the application of PBT for AMD and nine studies examining the application of PBT for diabetic macular edema (DME) were extracted from 60 candidate publications. Discussion Despite notable methodological differences between studies, PBT has been reported to treat certain DR and AMD patients. DR patients with center involving DME and VA ≥ 20/25 have demonstrated response to treatment. AMD patients at Age-Related Eye Disease Study Stages 2–4 with VA ≥20/200 have also shown response to treatment. Results of major clinical trials are pending. Conclusion PBT remains an emergent therapy with possible applications in DR and AMD. Further, high powered studies monitored by a neutral party with standard devices, treatment delivery and treatment timing are needed.

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Emerging Therapies in Nonexudative Age-Related Macular Degeneration in 2020

Cited by 17 publications

References 27 publications

Phase 1B study of the safety and tolerability of the mineralocorticoid fludrocortisone acetate in patients with geographical atrophy

Phase 1B study of the safety and tolerability of the mineralocorticoid fludrocortisone acetate in patients with geographical atrophy

Impaired Mitochondrial Function in iPSC-Retinal Pigment Epithelium with the Complement Factor H Polymorphism for Age-Related Macular Degeneration

Photobiomodulation Therapy for Age-Related Macular Degeneration and Diabetic Retinopathy: A Review

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