The event of drug supply platforms that supply sustained launch of therapeutic brokers within the retina represents an important evolution in ophthalmic observe.
Whereas the continuing emergence of efficient medication and biologics for the therapy of retinal circumstances has been an excellent boon to our sufferers, the burden of frequent intravitreal injections poses challenges to affected person adherence and can lead to suboptimal outcomes (Holz et al.).
Moreover, sustained-release supply of therapeutic brokers to focus on tissues can present constant publicity of therapeutic brokers with brief half-lives that may be impractical to ship through topical drop or injection (Kim et al.). Sustaining constant drug ranges ought to end in better consistency of illness management, avoiding, for instance, the sawtooth sample of fluid decision and recurrence resulting from peak and trough drug concentrations from shorter-term supply strategies (Eichenbaum et al.).
Whereas intravitreal platforms that ship corticosteroids, equivalent to Ozurdex (dexamethasone intravitreal implant 0.7 mg, AbbVie), Iluvien (fluocinolone acetonide intravitreal implant 0.19 mg, ANI Prescription drugs) and Retisert (fluocinolone acetonide intravitreal implant 0.59 mg, Bausch + Lomb), have been available on the market for years to deal with circumstances equivalent to macular edema and uveitis, current improvements within the supply of biologic therapies with sustained-release platforms present nice promise for treating a wide range of retinal circumstances.
Port supply system
In February 2021, the FDA accepted Susvimo (ranibizumab injection 100 mg/mL, Genentech) port supply system (PDS) implant for the therapy of neovascular age-related macular degeneration. Regardless of a voluntary recall in 2022, it was reintroduced to the market in 2024, and its approval was expanded for the therapy of diabetic macular edema in February.
The PDS differs from different ocular drug supply platforms by containing a refillable indwelling reservoir, which permits it to offer steady supply of ranibizumab into the vitreous over prolonged intervals of time, with constant launch charges over a number of refill exchanges. Scientific trials of the PDS demonstrated comparable anatomical and visible outcomes to month-to-month ranibizumab injections, and greater than 90% of sufferers in a single research most well-liked the PDS to ongoing intravitreal injections (Ranade et al.).
Whereas the PDS is presently used to ship ranibizumab solely, it might theoretically be used to produce different biologic therapies to the retina. That is an thrilling prospect, and I sit up for seeing future developments with this platform.
Travoprost intracameral implant
One other fascinating growth lately has been the approval of bioerodible sustained-release implants, most just lately iDose TR (travoprost intracameral implant 75 µg, Glaukos) to decrease IOP in sufferers with glaucoma or ocular hypertension.
The iDose TR is delivered through a transparent corneal incision and anchored by means of the trabecular meshwork into the sclera on the iridocorneal angle, the place it offers a steady provide of travoprost into the anterior chamber. In two part 3 trials spanning 12 months, the implant was discovered to offer sustained and statistically noninferior efficacy to timolol, and roughly 81% of sufferers who acquired the implant didn’t require using any extra topical IOP-lowering drugs whereas sustaining a good security profile (Singh et al.). This is a crucial growth as a result of traditionally affected person adherence to topical IOP-lowering drugs has been difficult (Nordstrom et al.). As enhancements to adherence might considerably delay glaucomatous illness development (Skalicky et al.), sustained-delivery approaches characterize an important step ahead within the long-term administration of this illness.
Encapsulated cell remedy
A 3rd groundbreaking growth has been the approval of encapsulated cell remedy (ECT)-based Encelto (revakinagene taroretcel-lwey, Neurotech Prescription drugs), which is the primary and solely FDA-approved therapy for adults with macular telangiectasia sort 2 (MacTel). In Encelto, genetically altered retinal pigment epithelial (RPE) cells are encapsulated in a semipermeable capsule that’s then implanted into the vitreous humor. After being secured to the sclera, the discharge of therapeutic proteins from the implant can simply get to the retina. These cells have a low metabolic charge and might subsequently subsist on vitamins already current within the intraocular surroundings (Tao).
The RPE cells in Encelto have been modified to supply ciliary neurotrophic issue (CNTF), a neuroprotective protein that has been demonstrated to sluggish the lack of photoreceptors that happens in sufferers with MacTel (Chew et al.). The outcomes of two multicenter, randomized, sham-controlled part 3 medical trials demonstrated a statistically important distinction in charge of change in ellipsoid zone space loss, a proxy measure for photoreceptor loss, from baseline in sufferers handled with Encelto in contrast with sham by means of 24 months (Albini). Encelto was additionally usually nicely tolerated, with nearly all of treatment-emergent ocular adversarial occasions being associated to surgical procedure. Moreover, the biologic exercise of the CNTF produced by ECT implants was famous to be steady for greater than a decade, highlighting the long-term utility of this strategy (Kauper et al.).
Encelto is contraindicated in sufferers with lively or suspected ocular or periocular infections or identified hypersensitivity to endothelial serum-free media.
Relating to useful outcomes, therapy with Encelto was proven to sluggish the retinal sensitivity loss on microperimetry and the speed of studying pace loss in contrast with sham remedy (Chew et al.).
Encelto represents a landmark in our area as the primary accepted therapy for adults with MacTel. It additionally demonstrates the good potential of ECT as a platform, because the brief intraocular half-life of CNTF (days) makes it impractical to manage through repeated intravitreal injection (Itkonen et al.). Just like the PDS, ECT has the potential for use to beat the challenges of delivering different therapeutic proteins to the again of the attention.
Finest practices to implant drug supply platforms
The process for implanting the PDS was refined all through the medical program to reduce issues equivalent to vitreous hemorrhage, implant match and conjunctival erosion/retraction. The approach requires meticulous consideration to particulars distinctive to the machine; thus, each particular coaching and preparation are crucial (Pieramici et al.).
Like many minimally invasive glaucoma surgical procedures, iDose TR administration might be carried out alongside cataract surgical procedure or as a stand-alone process, utilizing methods acquainted to the anterior section surgeon.
Within the case of Encelto, the surgical process makes use of customary vitreoretinal surgical procedure methods, however cautious consideration to the directions to be used are important to reduce post-insertion issues and guarantee favorable outcomes.
With any surgical implantation, the surgeon should pay attention to potential intraoperative and quick postoperative issues equivalent to hemorrhage and an infection. There are additionally long-term issues, together with suture erosion and implant migration, intrusion or extrusion, which will require revision or elimination; whereas these issues are rare, retina surgeons should be accustomed to them and conversant with how they’re managed.
Affected person communication can also be key; we should alert sufferers to the ocular floor signs that may recommend a suture erosion, and we should always advocate a low threshold for contacting the workplace with any new signs or considerations.
Conclusion
As extra long-acting retinal supply platforms are studied and dropped at market, we are able to sit up for significant enhancements in therapy burden and outcomes for our sufferers. Guaranteeing we stay updated with these gadgets and the methods used for implanting them will place us to offer the very best degree of look after our sufferers.
References:
- Albini TA. Section 3, multicenter, randomized, sham-controlled research of the efficacy and security of revakinagene taroretcel in macular telangiectasia sort 2. Introduced at: Retina World Congress; Might 9-12, 2024; Fort Lauderdale, Florida.
- Chew EY, et al. Ophthalmology. 2019;doi:10.1016/j.ophtha.2018.09.041.
- Eichenbaum D, et al. Retina. 2023;doi:10.1097/IAE.0000000000003699.
- Encelto. Bundle insert. Neurotech Prescription drugs; 2025.
- Encelto (revakinagene taroretcel-lwey) implant. Bundle insert. Neurotech Prescription drugs; 2025.
- FDA approves Genentech’s Susvimo as the primary and solely steady supply therapy for the main reason for diabetes-related blindness. https://www.gene.com/media/press-releases/15050/2025-02-04/fda-approves-genentechs-susvimo-as-the-f. Printed Feb. 4, 2025. Accessed April 1, 2025.
- Genentech to reintroduce Susvimo for individuals with moist age-related macular degeneration (AMD). https://www.gene.com/media/press-releases/15031/2024-07-08/genentech-to-reintroduce-susvimo-for-peo. Printed July 8, 2024. Accessed April 1, 2025.
- Glaukos publicizes FDA approval of iDose TR (travoprost intracameral implant). https://buyers.glaukos.com/buyers/information/news-details/2023/Glaukos-Publicizes-FDA-Approval-of-iDoseTR-travoprost-intracameral-implant/default.aspx. Printed Dec. 14, 2023. Accessed June 9, 2025.
- Holz FG, et al. Br J Ophthalmol. 2015;doi:10.1136/bjophthalmol-2014-305327.
- iDose TR (travoprost intracameral implant). Bundle insert. Glaukos; 2023.
- Iluvien (fluocinolone acetonide intravitreal implant). Bundle insert. Alimera Sciences; 2025.
- Itkonen J, et al. Pharmaceutics. 2020;doi:10.3390/pharmaceutics12070611.
- Kauper Ok, et al. Steady intraocular drug supply lasting over a decade: Ciliary neurotrophic issue (CNTF) secreted from neurotech’s NT-501 implanted in topics with retinal degenerative problems. Introduced at: Affiliation for Analysis in Imaginative and prescient and Ophthalmology assembly; April 23-27, 2023; New Orleans.
- Kim HM, et al. Pharmaceutics. 2021;doi:10.3390/pharmaceutics13010108.
- Neurotech’s Encelto (revakinagene taroretcel-Iwey) accepted by the FDA for the therapy of macular telangiectasia sort 2 (MacTel). https://www.neurotechpharmaceuticals.com/wp-content/uploads/Neurotech_Press-Release_BLA_Approval_FINAL.pdf. Printed March 6, 2025. Accessed April 1, 2025.
- Nordstrom BL, et al. Am J Ophthalmol. 2005;doi:10.1016/j.ajo.2005.04.051.
- Ozurdex (dexamethasone intravitreal implant). Bundle insert. AbbVie; 2024.
- Pieramici DJ, et al. Ophthalmic Surg Lasers Imaging Retina. 2022;doi:10.3928/23258160-20220408-01.
- Ranade SV, et al. Drug Deliv. 2022;doi:10.1080/10717544.2022.2069301.
- Retisert (fluocinolone acetonide intravitreal implant). Bundle insert. Bausch + Lomb; 2023.
- Singh IP, et al. Medication. 2024;doi:10.1007/s40265-024-02074-9.
- Skalicky SE, et al. Asia Pac J Ophthalmol (Phila). 2013;doi:10.1097/APO.0000000000000023.
- Tao W. Knowledgeable Opin Biol Ther. 2006;doi:10.1517/14712598.6.7.717.
For extra info:
Antonio Capone Jr., MD, a specialist in illnesses and surgical procedure of the retina and vitreous at Related Retinal Consultants in Royal Oak, Michigan, chief medical officer at EyeCare Companions and professor of ophthalmology at Oakland College William Beaumont Faculty of Drugs, might be reached at acaponejr@arcpc.web.
