Outside the Box, Inside the Pipeline

Glaucoma requires chronic, lifelong management. To overcome the limitations of current options and release the burden on patients and physicians, researchers are looking at novel therapeutic approaches—sometimes thinking outside the box.

Several companies are placing their efforts in developing more effective and stable implants targeting aqueous outflow either through subconjunctival space, Schlemm’s canal, cilio-scleral or suprachoroidal space, as well as devices for the automatisation and enhancement of selective laser trabeculoplasty, aiming to provide a more durable and precise IOP reduction through time and targeting a wider population of patients.¹

At the same time, to enhance existing treatment strategies, companies are also looking for alternative and drop-free drug delivery systems, improving patient adherence and decreasing patient burden either through injectable and dissolvable implants or polymer-based nanocarriers delivering NGF directly to the posterior segment.^2–3

Better monitoring and screening

Implementing home monitoring and telemedicine could be an invaluable support to treatment, allowing for rapid detection and progression assessment of an otherwise asymptomatic condition such as glaucoma. Keeping track of random IOP spikes is already a well-known challenge, and the demand for continuous monitoring is pressing companies to develop approaches to address this issue. A permanent implantable device called Eyemate and an IOP-detecting contact lens called Triggerfish already

have the CE mark. On the other hand, South Korea’s Pohang University of Science and Technology is developing a contact lens capable of both detecting IOP and administering drugs in an exquisite theranostic fashion.^4–6

Genetic screening, gene therapy, and genome editing will play a key role in the future treatment of glaucoma. According to Tonti (Dell’Omo, et al.), existing therapeutic approaches could be optimised in synergy with epigenetic regulator targeting, leading to more patient-tailored treatment strategies.⁷ Although still only in its preclinical phase for different anterior segment conditions, gene therapy could become a game-changing tool in the glaucoma specialists’ armamentarium, shortly followed by CRISPR-Cas9 gene editing, both for neuroprotection and disease treatment.

The next out-of-the-box treatment in the pipeline could be stem cell therapy. In a recent study published in Proceedings of the National Academy of Sciences of the United States of America (PNAS), researchers of the Schepens Eye Research Institute of Mass Eye and Ear were able to collect stem cells from blood, turning them into retinal ganglion cells capable of migrating and surviving into the eye’s retina.⁸ The study was performed in in vivo mice models, and the positive outcomes are highly promising.

1. Chan L, Moster MR, Bicket AK, et al. “New Devices in Glaucoma,” Ophthalmol Ther, 2023; 12: 2381–2395. https://doi.org/10.1007/s40123-023-00780-3

2. Sarkisian SR, Ang RE, Lee AM, Berdahl JP, Heersink SB, Burden JH, Doan LV, Stephens KG, Applegate D, Kothe AC, Usner DW, Katz LJ, Navratil T. “Travoprost Intracameral Implant for Open-Angle Glaucoma or Ocular Hypertension: 12-Month Results of a Randomized, Double-Masked Trial,” Ophthalmol Ther, 2024 Apr; 13(4): 995–1014. doi: 10.1007/s40123-024-00898-y. Epub 2024 Feb 12.

3. Colucci P, Giannaccini M, Baggiani M, Kennedy BN, Dente L, Raffa V, Gabellini C. “Neuroprotective Nanoparticles Targeting the Retina: A Polymeric Platform for Ocular Drug Delivery Applications,” Pharmaceutics, 2023; 15(4): 1096. https://doi.org/10.3390/pharmaceutics15041096

4. Szurman P, Gillmann K, Seuthe AM, Dick HB, Hoffmann EM, Mermoud A, Mackert MJ, Weinreb RN, Rao HL, Mansouri K; EYEMATE-SC Study Group. “EYEMATE-SC Trial: Twelve-Month Safety, Performance, and Accuracy of a Suprachoroidal Sensor for Telemetric Measurement of Intraocular Pressure,” Ophthalmology, 2023 Mar; 130(3): 304–312. doi:10.1016/j.ophtha.2022.09.021. Epub 2022 Oct 3.

5. Dunbar GE, Shen BY, Aref AA. “The Sensimed Triggerfish contact lens sensor: efficacy, safety, and patient perspectives,” Clin Ophthalmol, 2017 May 8; 11: 875–882. doi:10.2147/OPTH.S109708.

6. Kim TY, Mok JW, Hong SH, et al. “Wireless theranostic smart contact lens for monitoring and control of intraocular pressure in glaucoma,” Nat Commun, 2022; 13: 6801. https://doi.org/10.1038/s41467-022-34597-8

7. Tonti E, Dell’Omo R, Filippelli M, Spadea L, Salati C, Gagliano C, Musa M, Zeppieri M. “Exploring Epigenetic Modifications as Potential Biomarkers and Therapeutic Targets in Glaucoma,” Int J Mol Sci, 2024 Feb 29; 25(5): 2822. doi: 10.3390/ijms25052822.

8. Soucy JR, Todd L, Kriukov E, Phay M, Malechka VV, Rivera JD, Reh TA, Baranov P. “Controlling donor and newborn neuron migration and maturation in the eye through microenvironment engineering,” Proc Natl Acad Sci, 2023 Nov 14; 120(46): e2302089120. doi: 10.1073/pnas.2302089120.