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Pharmaceuticals
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Novel Treatments and Technologies for Retinal Diseases
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Novel Treatments and Technologies for Retinal Diseases

A special issue of Pharmaceuticals (ISSN 1424-8247). This special issue belongs to the section "Pharmaceutical Technology".

Deadline for manuscript submissions: 31 May 2025 | Viewed by 6685

Special Issue Editor

Dr. Michael John Tolentino

E-Mail Website
Guest Editor
1. Department of Ophthalmology, University of Central Florida College of Medicine, Orlando, FL 32827, USA
2. Department of Ophthalmology, Orlando College of Osteopathic Medicine, Orlando, FL 34787, USA
3. Aviceda Therapeutics, Cambridge, MA 02142, USA
Interests: age related macular degeneration; diabetic retinopathy; retinal degeneration; innate immune modulation; glyobiology; glyco-mimetic therapeutics; nanoparticles; non-viral/viral gene therapy; RNA interference; artificial intelligence; imaging biomarker; neuroprotection; clinical trials; ocular drug delivery; regenerative medicine; complement; macrophage; microglia; anti-VEGF

Special Issue Information

Dear Colleagues,

Recent advances in the pathophysiologic understanding, imaging biomarkers, artificial intelligence and clinical trial design of retinal diseases combined with technological advancements in aptamer antagonists, non-viral/viral gene-therapy, RNA interference, high affinity antibodies, receptor traps, and nanoparticle glyco-mimetics have led to several FDA-approved therapies for formerly unmet medical needs. These FDA approvals combined with the prevalence of these retinal diseases have led to an increase in the research interest in retinal diseases. The purpose of this Special Issue is to provide a snapshot of all aspects of these advancements from basic science to the identification of pathogenic molecular targets, the development of novel classes of therapeutics, the development of clinically relevant pre-clinical models, the use of artificial intelligence to determine when and how we use these novel therapeutics, and the validation of new FDA-approved endpoints. We aim for a focused yet comprehensive Special Issue.

Dr. Michael John Tolentino
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Pharmaceuticals is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • age-related macular degeneration
  • diabetic retinopathy
  • retinal degeneration
  • novel therapeutics
  • imaging biomarkers
  • artificial intelligence
  • clinical trials

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Published Papers (4 papers)

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Research

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19 pages, 2710 KiB  
Article
PolySialic Acid Nanoparticles Actuate Complement-Factor-H-Mediated Inhibition of the Alternative Complement Pathway: A Safer Potential Therapy for Age-Related Macular Degeneration
by Sheri L. Peterson, Anitha Krishnan, Diyan Patel, Ali Khanehzar, Amit Lad, Jutamas Shaughnessy, Sanjay Ram, David Callanan, Derek Kunimoto, Mohamed A. Genead and Michael J. Tolentino
Pharmaceuticals 2024, 17(4), 517; https://doi.org/10.3390/ph17040517 - 17 Apr 2024
Cited by 5 | Viewed by 2330
Abstract
The alternative pathway of the complement system is implicated in the etiology of age-related macular degeneration (AMD). Complement depletion with pegcetacoplan and avacincaptad pegol are FDA-approved treatments for geographic atrophy in AMD that, while effective, have clinically observed risks of choroidal neovascular (CNV) [...] Read more.
The alternative pathway of the complement system is implicated in the etiology of age-related macular degeneration (AMD). Complement depletion with pegcetacoplan and avacincaptad pegol are FDA-approved treatments for geographic atrophy in AMD that, while effective, have clinically observed risks of choroidal neovascular (CNV) conversion, optic neuritis, and retinal vasculitis, leaving room for other equally efficacious but safer therapeutics, including Poly Sialic acid (PSA) nanoparticle (PolySia-NP)-actuated complement factor H (CFH) alternative pathway inhibition. Our previous paper demonstrated that PolySia-NP inhibits pro-inflammatory polarization and cytokine release. Here, we extend these findings by investigating the therapeutic potential of PolySia-NP to attenuate the alternative complement pathway. First, we show that PolySia-NP binds CFH and enhances affinity to C3b. Next, we demonstrate that PolySia-NP treatment of human serum suppresses alternative pathway hemolytic activity and C3b deposition. Further, we show that treating human macrophages with PolySia-NP is non-toxic and reduces markers of complement activity. Finally, we describe PolySia-NP-treatment-induced decreases in neovascularization and inflammatory response in a laser-induced CNV mouse model of neovascular AMD. In conclusion, PolySia-NP suppresses alternative pathway complement activity in human serum, human macrophage, and mouse CNV without increasing neovascularization. Full article
(This article belongs to the Special Issue Novel Treatments and Technologies for Retinal Diseases)
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Review

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25 pages, 1838 KiB  
Review
Preclinical Retinal Disease Models: Applications in Drug Development and Translational Research
by Sudha Priya Soundara Pandi, Hanagh Winter, Madeleine R. Smith, Kevin Harkin and James Bojdo
Pharmaceuticals 2025, 18(3), 293; https://doi.org/10.3390/ph18030293 - 21 Feb 2025
Viewed by 950
Abstract
Retinal models play a pivotal role in translational drug development, bridging preclinical research and therapeutic applications for both ocular and systemic diseases. This review highlights the retina as an ideal organ for studying advanced therapies, thanks to its immune privilege, vascular and neuronal [...] Read more.
Retinal models play a pivotal role in translational drug development, bridging preclinical research and therapeutic applications for both ocular and systemic diseases. This review highlights the retina as an ideal organ for studying advanced therapies, thanks to its immune privilege, vascular and neuronal networks, accessibility, and advanced imaging capabilities. Preclinical retinal disease models offer unparalleled insights into inflammation, angiogenesis, fibrosis, and hypoxia, utilizing clinically translatable bioimaging tools like fundoscopy, optical coherence tomography, confocal scanning laser ophthalmoscopy, fluorescein angiography, optokinetic tracking, and electroretinography. These models have driven innovations in anti-inflammatory, anti-angiogenic, and neuroprotective strategies, with broader implications for systemic diseases such as rheumatoid arthritis, Alzheimer’s, and fibrosis-related conditions. By emphasizing the integration of the 3Rs principles and novel imaging modalities, this review highlights how retinal research not only enhances therapeutic precision but also minimizes ethical concerns, paving the way for more predictive and human-relevant approaches in drug development. Full article
(This article belongs to the Special Issue Novel Treatments and Technologies for Retinal Diseases)
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Figure 1

20 pages, 3725 KiB  
Review
Rethinking Clinical Trials in Age-Related Macular Degeneration: How AI-Based OCT Analysis Can Support Successful Outcomes
by Marie Louise Enzendorfer, Merle Tratnig-Frankl, Anna Eidenberger, Johannes Schrittwieser, Lukas Kuchernig and Ursula Schmidt-Erfurth
Pharmaceuticals 2025, 18(3), 284; https://doi.org/10.3390/ph18030284 - 20 Feb 2025
Viewed by 775
Abstract
Age-related macular degeneration (AMD) is a leading cause of blindness in the developed world. Due to an aging population, its prevalence is expected to increase, making novel and optimized therapy options imperative. However, both late-stage forms of the disease, neovascular AMD (nAMD) and [...] Read more.
Age-related macular degeneration (AMD) is a leading cause of blindness in the developed world. Due to an aging population, its prevalence is expected to increase, making novel and optimized therapy options imperative. However, both late-stage forms of the disease, neovascular AMD (nAMD) and geographic atrophy (GA), exhibit considerable variability in disease progression and treatment response, complicating the evaluation of therapeutic efficacy and making it difficult to design clinical trials that are both inclusive and statistically robust. Traditional trial designs frequently rely on generalized endpoints that may not fully capture the nuanced benefits of treatment, particularly in diseases like GA, where functional improvements can be gradual or subtle. Artificial intelligence (AI) has the potential to address these issues by identifying novel, condition-specific biomarkers or endpoints, enabling precise patient stratification and improving recruitment strategies. By providing an overview of the advances and application of AI-based optical coherence tomography analysis in the context of AMD clinical trials, this review highlights the transformative potential of AI in optimizing clinical trial outcomes for patients with nAMD or GA secondary to AMD. Full article
(This article belongs to the Special Issue Novel Treatments and Technologies for Retinal Diseases)
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Graphical abstract

17 pages, 338 KiB  
Review
New Therapeutic Strategies in Retinal Vascular Diseases: A Lipid Target, Phosphatidylserine, and Annexin A5—A Future Theranostic Pairing in Ophthalmology
by Anna Frostegård and Anders Haegerstrand
Pharmaceuticals 2024, 17(8), 979; https://doi.org/10.3390/ph17080979 - 24 Jul 2024
Viewed by 2030
Abstract
Despite progress in the management of patients with retinal vascular and degenerative diseases, there is still an unmet clinical need for safe and effective therapeutic options with novel mechanisms of action. Recent mechanistic insights into the pathogenesis of retinal diseases with a prominent [...] Read more.
Despite progress in the management of patients with retinal vascular and degenerative diseases, there is still an unmet clinical need for safe and effective therapeutic options with novel mechanisms of action. Recent mechanistic insights into the pathogenesis of retinal diseases with a prominent vascular component, such as retinal vein occlusion (RVO), diabetic retinopathy (DR) and wet age-related macular degeneration (AMD), may open up new treatment paradigms that reach beyond the inhibition of vascular endothelial growth factor (VEGF). Phosphatidylserine (PS) is a novel lipid target that is linked to the pathophysiology of several human diseases, including retinal diseases. PS acts upstream of VEGF and complement signaling pathways. Annexin A5 is a protein that targets PS and inhibits PS signaling. This review explores the current understanding of the potential roles of PS as a target and Annexin A5 as a therapeutic. The clinical development status of Annexin A5 as a therapeutic and the potential utility of PS-Annexin A5 as a theranostic pairing in retinal vascular conditions in particular is described. Full article
(This article belongs to the Special Issue Novel Treatments and Technologies for Retinal Diseases)
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