CILIOSCLERAL INTERPOSITION (CID) DEVICE

 

• Ciliatech, a France based company has developed a novel glaucoma implant.
• Known as the cilioscleral-interposition (CID) device, it is a unique non-resorbable glaucoma implant.
• It is a single-piece implant, made from 26% hydrophilic acrylic, which ensures long-term biocompatibility.
• It consists of a specifically designed 6mm long, 4 mm wide, and 200µm thick plate.
• The device’s two faces and edges are designed with grooves and corrugations to maximize the outflow from the anterior chamber and its circulation to the choroid and the sclera-conjunctival vessels.

OCT image of CID implant

• Spares the conjunctiva, which is only incised over the scleral incision site.
• Incurs no Endothelial Cell Loss (ECL): the implant does not enter the anterior chamber of the eye, as the wall that separates the anterior chamber from the supraciliary space is not cut: there is zero risk of altering the corneal endothelium.
• Generates very low post-operative inflammation; the surgical technique and the implant do not provoke ciliary body reaction: the anatomical compartments of the anterior segment are not modified, resulting in fewer adverse events and thus better patient post-operative comfort.
• Does not create a bleb: scleral incisions are sutured watertight to maintain the outflow under the sclera. As such, the surgical technique and the implant cannot generate a subconjunctival bleb and its associated complications (heavy post-op monitoring, cyst, fibrosis, use of antimetabolites, etc.).
• ‘No loss of chance’: should a second surgery be needed, CID surgery preserves the eye anatomy (anterior segment and conjunctiva); another interventional act (laser, stent, trabeculectomy or GDD) can be performed without difficulty.
• Two cohorts of 20 and 22 patients in Yerevan, Armenia, living with open angle glaucoma, participated in the studies. They were operated on with one of the first versions of Ciliatech’s implant (SV13) in a monocentric study.
• Based on internal data: interim results at 12M / 6M follow-up SAFARI 1 / SAFARI 2 studies respectively, the implant achieves an IOP in the mid to low teens (15 mmHg and lower).
• There is significant IOP reduction >33%.
• Medication reduction >90% at 12 months was also reported in the studies.
• No treatment failure (no reoperation) at 12 months in 42 patients: 89% of patients were medication free.
• Spares the anterior chamber and the ciliary muscle root.
• Removes a local obstacle to uveoscleral outflow. This allows aqueous humour resorption at the supraciliary and suprachoroidal spaces.

https://www.cilia.tech/

 

THERANOSTIC SMART CONTACT LENS

 

Smart contact lenses can provide a new paradigm in glaucoma as a promising alternative to conventional management methods with non-invasive, continuous IOP monitoring and on-demand drug delivery.

THERANOSTIC CONTACT LENS

In particular, recent smart contact lenses based on strain gauges, resonant, microfluidic, and optical systems have attracted great attention for continuous IOP monitoring including Triggerfish which achieved Food and Drug Administration approval in 2016 for the first time.

Here, we report a highly integrated theranostic smart contact lens for both monitoring and control of IOP in glaucoma.

The theranostic smart contact lens comprises of a gold hollow nanowire (AuHNW) based IOP sensor, a flexible drug delivery system (DDS), wireless circuits, and a ultra-low power application-specific integrated circuit (ASIC) chip.

The flexible DDS could release timolol on-demand by the electrochemical dissolution of gold channels.

The therapeutic effect of timolol released from the theranostic smart contact lens was analyzed and compared with that of eye drop (0.5% Timoptic) in glaucoma-induced rabbits. The right eyes of glaucoma rabbits were treated by eye drop every day or timolol released from the smart contact lens every other day for 2 weeks. The left eyes of glaucoma rabbits were treated with PBS as a negative control.

THE LENS IN RABBIT EYE

Retina histology revealed that the retina thickness was similar with that of the normal in both treatment groups. However, the thickness of retina was thin in the case of non-treatment groups. Especially, there were significant differences in ganglion cell layers (GCL) with and without treatment. Furthermore, the inner nuclear layers (INL) of non-treatment groups were unstable and thinned compared to those of normal and treatment groups.

Upon the drug treatment with smart contact lens, the IOP decreased quickly, maintained within the reduced IOP for 18 h, and returned to the initial IOP level after 24 h.

Finally, the IOP level was controlled with the theranostic smart contact lens by monitoring IOP and releasing timolol every other day for 5 days.

On the first day, because the IOP level was in the high IOP range (above 22 mmHg), timolol was released out to reduce IOP and the IOP was reduced below the normal range. On the third day, IOP was still above the normal range and the released timolol could reduce the IOP level near the normal range. On the final day, the IOP level was in the normal range and timolol was not released out from the smart contact lens. All these results confirmed the feasibility of the fully integrated theranostic smart contact lens.

FERROPTOSIS: A DISTINCT CELL DEATH PATHWAY IN GLAUCOMA

Regulated cell death is a genetically programmed cell death associated with the maintenance of homeostasis and disease development. 

Apoptosis, pyroptosis, and necroptosis are classical forms of regulated cell death that play important roles in various diseases. 

Ferroptosis was a regulated cell death described by Dixon et al. who used elastin to treat cancer cells containing oncogene mutations. 

They found an iron-dependent and lipid peroxidation-triggered cell death pathway, which relies on iron-generated reactive oxygen species.

The pathway was independent of caspase, adenosine triphosphate exhaustion, mitochondria reactive oxygen species generation, the permeability of the mitochondria outer membrane, and increased concentration of intracellular calcium ion. 

This distinct form of cell death is significantly different from other forms of cell death morphologically, biochemically, genetically, and metabolically. 

Three mainstream pathways have been identified in ferroptosis: glutathione peroxidase 4-glutathione (GPx-4-GSH) pathway, ferroptosis suppressor protein 1-ubiquinone-reduced nicotinamide adenine dinucleotide phosphate [FSP1-CoQ-NAD(P)H] axis, and dihydroorotate dehydrogenase (DHODH) signaling.

https://journals.lww.com/nrronline/Fulltext/2023/03000/Ferroptosis_and_glaucoma__implications_in_retinal.24.aspx

PAUL GLAUCOMA IMPLANT: OLD WINE IN AN OLD BOTTLE?

 

Over the last few years, a number of companies have introduced their models of Glaucoma Drainage Devices (GDDs). In a market dominated by the Ahmed Glaucoma Valve (AGV) and the Baerveldt Glaucoma Implant (BGI), these new players have been unable to bring any exciting innovations to present a formidable challenge to the two trusted brands.

The Paul Glaucoma Implant (PGI) is a valveless GDD designed by Professor Paul Chew from Singapore. With just a few minor changes to the other valveless implants already available, the PGI appears to be a case of old wine in a new bottle or is it old wine in an old bottle?

The PGI is manufactured by Advanced Ophthalmic Innovations Pte Ltd, Singapore from medical implantable grade silicone.

PAUL Glaucoma Implant

The plate of the PGI has a length of 44.9 mm, width of 23 mm and an extraocular plate surface area of 342.1 mm².

The PGI has a shorter wingspan compared with the BGI but extends further posteriorly due to a wider width. The plate surface area is smaller than the BGI, but larger than the AGV.

The anteroposterior depth of the PGI is larger compared to that of the BGI which allows the plate to extend further back, while the shorter breadth (wingspan) reduces the area of the plate tucked under the recti muscles which may theoretically reduce the postoperative risk of strabismus and diplopia.

The internal diameter of the PGI is the smallest amongst the 3 tube shunts at 0.127 m, about one third the diameter of both the AGV and BGI. The smaller internal tube calibre increased aqueous flow resistance which theoretically reduces the risk of postoperative hypotony. The overall slimmer tube caliber allows for a lower tube profile protruding above the sclera and theoretically reduces risk of conjunctival erosion while also reducing the risk of tube-endothelium contact and damage. The lumen can be easily occluded using a 6/0 or 7/0 polypropylene stent compared to the 3/0 which is usually used to occlude the tube in the BGI.

Comparison of the 3 GDDs

In a 2-year study performed by the innovators, postoperative complications included shallow anterior chamber which was self-limiting (n=10 [22.2%]), hypotony requiring intervention (n=4 [8.9%]) and tube occlusion (n=4 [8.9%]).

One eye developed an inferior retinal detachment requiring vitrectomy a month after implantation but this was not directly related to the PGI surgery.

Of the 4 eyes with tube occlusion, 2 were occluded by iris which was treated with argon laser iridoplasty, 1 was blocked by fibrin and required an anterior chamber washout with tube flushing, and 1 which was blocked by vitreous required an anterior vitrectomy with tube flushing twice.

All cases of self-limiting shallow anterior chamber resolved within a month of the surgery.

For the 4 eyes with hypotony that required anterior chamber injection of viscoelastic, 2 required more than 1 injection of viscoelastic and 1 had subsequent intervention in the form of anterior vitrectomy and tube flushing for tube occlusion from vitreous.

One eye had persistent hypotony at 2 years, which was complicated by blunt trauma to the eye about 1.5 years postsurgery.

One eye underwent tube repositioning as the tube was felt to be too anterior, with endothelial cell count showing a downward trend from 2100 to 1400 cells/mm².

There were no serious complications and no eyes required explantation of the PGI.

In conclusion, the Paul Glaucoma Implant does not appear to present any significant practical advantages compared to the presently popular GDDs. However, like any other device, longer and multi-center studies may throw more light on the effectiveness of PGI.

https://journals.lww.com/glaucomajournal/Fulltext/2022/06000/Two_Year_Outcomes_of_the_Paul_Glaucoma_Implant_for.13.aspx?WT.mc_id=HPxADx20100319xMP