iStent MIGS device

INTRODUCTION

The iStent is the smallest device ever implanted in the human body. This minimally invasive glaucoma surgery (MIGS) device is devised to bypass the obstructed trabecular meshwork (TM) and allow flow of aqueous from the anterior chamber into the Schlemm’s canal. The instrument was devised by the Glaukos company in the USA and one of the earliest published report was by Spiegel et al. in 2007. The first generation iStent was 1 mm in length and 0.3 mm in height, making it the smallest device approved for implantation by FDA in 2012. This stent is shaped like a snorkel with retention ridges. It is made from an implant grade, heparin-coated titanium alloy and is inserted in the TM manually. The stent is implanted by an ab interno approach guided by gonioscopy.

Subsequently, in 2018 the company came up with the iStent Inject. This device comes with two stents within the injector, as opposed to the first-generation device that had only one stent. Similarly, it is also composed of implant-grade titanium and is 360 μm in length and 230 μm in width, which is one-third the size of the first-generation iStent. Unlike the snorkel shaped first generation iStent, the second generation stent contains a central inlet and multiple outlets designed to provide multidirectional flow through Schlemm’s canal.

Studies regarding these devices have usually been conducted utilizing combined cataract surgery with iStent implantation. Most of the studies have shown significant reduction in intra-ocular pressure (IOP) and medication usage. One of the major studies regarding this device has been the US iStent Study Group. The study compared combined cataract surgery with a single iStent implantation versus phacoemulsification alone. 70% patients in the combined group achieved IOP <22 mmHg without medications compared to 50% in the phacoemulsification alone group (p <0.001). At 12 months, the number of patients requiring medications in the combined group was 15% compared to 35% in the phacoemulsification alone group (p=0.001). These effects were also found in a follow-up study conducted at 24 months.

Studies on solo iStent implantation have also demonstrated >20% IOP lowering until 24-months of follow up. Studies have compared 1,2 and 3 iStent implantations. It was found that 2 and 3 iStent implantation led to nearly 41% IOP reduction, compared to 31% by single stent use.

Therefore, it can be concluded that iStent is a useful trabecular bypass MIGS device which can be effective in IOP lowering as a solo or combined procedure.

SURGICAL TECHNIQUE

The surgical steps for iStent implantation are available in detail elsewhere (See link). Here, the steps are given in brief. In the first generation iStent, the anterior chamber is filled with viscoelastic. A temporal clear-corneal incision is made. If combined with cataract surgery the same incision as the one for phacoemulsification can be used. The iStent on its injector is pushed into the AC and using a gonioscope to guide, is directed towards the nasal angle in such a way that the snorkel is facing downwards. The stent enters the TM and with a sideways motion of the hand the device is pushed deep inside. Subsequently, the inserter button is pressed, allowing the device to settle into the position. Small adjustments are made by tapping the end of the snorkel by the inserter. Finally, the inserter is taken out of the eye and the AC cleared of the viscoelastic.

The iStent Inject comes with 2 pre-loaded implants. The surgeon enters the eye from the temporal clear-corneal incision and using the gonioprism reaches the TM. Then the device is brought into approximation at the desired position and the button pressed without any side to side movement of the hand to allow the implant to be delivered into the desired spot. The second stent is then implanted similarly 2-3 clock hours away.

https://www.youtube.com/watch?v=LCDE0NB6S2Y

COMPLICATIONS

Most studies did not report any complication from the iStent per se and most were attributed to cataract surgery. A few studies have reported on stent occlusion or malposition occurring in 2.6-18% patients. The new iStent Inject provides multiple openings to minimize the possibility of occlusion. Mild bleeding during implantation of the iStent is common, but usually resolves spontaneously.

A study was conducted in Canada regarding cost effectiveness of the device.  The potential savings of the iStent compared to a 2-drug regimen over a 6-year period was CA$1272 and CA$2124 when using 3 drugs.

CONCLUSION

 The iStent is a useful addition to our choice of MIGS devices. It is technically easy to use, efficient and safe.

KAHOOK DUAL BLADE vs iSTENT: A META-ANALYSIS

 

The Kahook Dual Blade (KDB) is a modern goniotomy device. The goal for inventing the KDB device was to find a better and more efficient method for removing a complete strip of trabecular meshwork (TM) using an ab interno approach while minimizing damage to surrounding tissues.

CHECK LINK: https://ourgsc.blogspot.com/search?q=kahook

The iStent is a minimally invasive glaucoma surgery (MIGS) device devised to bypass the obstructed TM and allow the flow of aqueous from the anterior chamber into the Schlemm’s canal.

CHECK LINK: https://ourgsc.blogspot.com/search?q=iStent

A systematic review and meta-analysis comparing the KDB with iStent implantation with phacoemulsification was done by Guedes et al.

Fourteen studies were included with a total of 1959 eyes (958 phaco-KDB, and 1000 phaco-Stent including 753 phaco-iStent and 207 phaco-iStent inject).

The combined findings showed significantly higher rates of surgical success in the phaco-KDB group versus the phaco-Stent group (odds ratio: 0.68; 95% CI: 0.50 to 0.92; P = 0.01; I2 = 40%), and greater IOP reduction in the phaco-KDB group versus the phaco-Stent group at month 6 (MD: 1.13 mm Hg; 95% CI: 0.43 to 1.83; P = 0.002; I2 = 51%).

By month 12, both groups demonstrated similar IOP reduction. Subgroup analysis at month 12 showed greater IOP reduction in the phaco-KDB group versus the phaco-iStent group (MD: 1.69 mm Hg; 95% CI: 0.44 to 2.95; P = 0.008; I2 = 74%). However, compared with the phaco iStent inject group, there was no significant difference in IOP reduction (MD: −0.72 mm Hg; 95% CI: −3.69 to 2.24; P = 0.63; I2 = 64%). Medication reduction and the incidence of adverse events were comparable between groups.

RESULT:

The study concluded that KDB goniotomy may offer better surgical success compared with Stent implantation when used in combination with phacoemulsification. KDB goniotomy demonstrated better IOP reduction at month 12 compared with iStent. However, iStent inject showed a similar IOP reduction to KDB.

REFERENCE:

Guedes J, Amaral DC, de Oliveira Caneca K, Cassins Aguiar EH, de Oliveira LN, Mora-Paez DJ, Cyrino LG, Louzada RN, Moster MR, Myers JS, Schuman JS, Shukla AG, Shalaby WS. Kahook Dual Blade Goniotomy Versus iStent Implantation Combined With Phacoemulsification: A Systematic Review and Meta-Analysis. J Glaucoma. 2025 Mar 1;34(3):232-247. doi: 10.1097/IJG.0000000000002522. Epub 2024 Dec 9. PMID: 39641580.

iDose TR Travoprost intracameral implant

 

Glaukos Corporation, the company which developed the iStent device, has announced the FDA approval of their single administration iDose TR travoprost intracameral implant.

The device is made from medical-grade titanium and measures 1.8 mm × 0.5 mm. It is implanted using a technique similar to many MIGS procedures. A gonioprism is used to identify the anterior chamber (AC) angle, a 2.2 mm incision is made in clear cornea, the AC is filled with a cohesive viscoelastic and the device is implanted through the trabecular meshwork and the back of the Schlemm’s canal directly into the scleral tissue. The device is held in place by a scleral anchor. After the end of the specified period, the device is replaced by a new one. According to some, the device can be used for 4-5 years.

The device has a membrane-bound reservoir of 75 mcg travoprost which diffuses continuously into the anterior chamber. There are two iDose TR models available, which have two different rates of drug elution (referred to as fast- and slow-release iDose TR models). This drug-delivery platform circumvents the patient compliance issue which plagues many glaucoma patients.

Contraindications:

iDose TR is contraindicated in patients with active or suspected ocular or periocular infections, patients with corneal endothelial cell dystrophy (e.g., Fuch’s Dystrophy, corneal guttatae), patients with prior corneal transplantation, or endothelial cell transplants (e.g., Descemet’s Stripping Automated Endothelial Keratoplasty [DSAEK]), patients with hypersensitivity to travoprost or to any other components of the product.

Warnings and Precautions:

iDose TR should be used with caution in patients with narrow angles or other angle abnormalities. Monitor patients routinely to confirm the location of the iDose TR at the site of administration. Increased pigmentation of the iris can occur. Iris pigmentation is likely to be permanent.

Adverse Reactions:

In controlled studies, the most common ocular adverse reactions reported in 2% to 6% of patients were increases in intraocular pressure, iritis, dry eye, visual field defects, eye pain, ocular hyperaemia, and reduced visual acuity.

Studies:

The FDA approval is based on results from two prospective, randomized, multicenter, double-masked, Phase 3 pivotal trials (GC-010 and GC-012) designed to compare the safety and efficacy of a single administration of one of two iDose TR models with different travoprost release rates (referred to as the fast- and slow-release iDose TR models, respectively) to topical timolol ophthalmic solution, 0.5% BID (twice a day), in reducing IOP in subjects with open-angle glaucoma or ocular hypertension. In total, the Phase 3 trials randomized 1,150 subjects across 89 clinical sites. The FDA approval and Phase 3 data referenced below is for the slow-release iDose TR model, consistent with the company’s NDA submission and commercialization plans.

Both Phase 3 trials successfully achieved the pre-specified primary efficacy endpoints through 3 months and demonstrated a favorable tolerability and safety profile through 12 months. IOP reductions from baseline over the first 3 months were 6.6-8.4 mmHg in the iDose TR arm, versus 6.5-7.7 mmHg in the timolol control arm.

 iDose TR demonstrated non-inferiority to timolol ophthalmic solution in IOP reduction during the first 3 months. The FDA also noted that subsequently iDose TR did not demonstrate non-inferiority over the next 9 months.

At 12 months, 81% of iDose TR subjects were completely free of IOP-lowering topical medications across both trials. In both trials, iDose TR demonstrated excellent tolerability and subject retention with 98% of iDose TR subjects continuing in the trial at 12 months, versus 95% of timolol control subjects. In controlled studies, the most common ocular adverse reactions reported in 2% to 6% of iDose TR patients were increases in intraocular pressure, iritis, dry eye, and visual field defects, most of which were mild and transient in nature.

INÊS FIGUEIREDO PEREIRA: RESEARCHER IN FOCUS

 

Dr. Inês Figueiredo Pereira is an Assistant Professor in the Microsystems group at the Eindhoven University of Technology (TU/e), Netherlands. She is credited with two different minimally invasive smart glaucoma implants.

Dr. Inês Figueiredo Pereira

 

Her expertise encompasses biomaterials, micro and nanotechnology, microfabrication, sensors and actuators, soft microvalves, stimuli-responsive materials, and microfluidics. Her research is dedicated to the advancement of wearable and implantable medical devices for healthcare applications, with a specific focus on enhancing diagnostics, disease prevention, and improving treatment outcomes.

As part of her research, she performed numerical simulation studies to assess the feasibility of using a glaucoma implant with an adjustable hydrodynamic resistance to regulate IOP in glaucoma patients. The model determines the ideal hydrodynamic resistance that a glaucoma implant must have to overcome the two most common postoperative complications–bleb scarring and hypotony. 

https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0273672

“Results from the simulations provided valuable insights that allowed for the development of a magnetically actuated glaucoma implant that can be non-invasively and repeatedly adjusted to different IOP conditions even after implantation,” notes Figueiredo Pereira.

 

Smart glaucoma implant

https://doi.org/10.1038/s41378-023-00561-9

Adjustment is achieved by integrating a magnetic microvalve in the implant, which can open or close fluidic channels, and thus change the hydrodynamic resistance of the implant when needed, and all by using a simple external magnet. “With this valving system, the IOP can be tuned according to a patient’s needs,” says Dr. Figueiredo Pereira.

Working of the smart glaucoma implant

She also developed a new biodegradable and minimally invasive glaucoma implant, which is approximately the same size as the world’s smallest medical device known to be implanted in the human body, which is the iStent Inject W from the company Glaukos. “The implant from Glaukos is a permanent and metallic implant, whereas ours is inspired by their implant but it is based on a polymer material (polycarbonate-bisamide or PC-BA) making it biodegradable’, remarks the researcher.

  

Biodegradable implant

“We anticipate that our implant will slowly degrade and then be absorbed by the body over time, leaving behind a natural pathway for fluid drainage,” says Figueiredo Pereira. “This biodegradable glaucoma implant provides a promising new approach for restoring outflow in a more natural way.” 

PUBLICATIONS:

https://www.tue.nl/en/research/researchers/ines-figueiredo-pereira

https://doi.org/10.1038/s41433-021-01595-x

https://research.tue.nl/nl/publications/a-model-for-designing-intraocular-pressure-regulating-glaucoma-im/?_gl=1*qrvniu*_ga*MTA5OTgwODE3Ny4xNjk0NDQ2MDgz*_ga_JN37M497TT*MTY5NTE5Nzc4NS41LjEuMTY5NTE5ODEyOS41MC4wLjA

https://www.tue.nl/en/news-and-events/news-overview/deze-glaucoomimplantaten-zijn-slim-en-veel-gemakkelijker-in-te-brengen

AHMED CLEARPATH DEVICE

Guest author

SUMERA SAGHEER

Ajmal Khan Tibbiya College

Aligarh- India

INTRODUCTION:

Minimally Invasive Glaucoma Surgery (MIGS) devices such as the ExPress Mini Shunt and Glaukos iStent provide ease of use for the surgeon. However, they allow only modest reductions in intra-ocular pressure (IOP). Therefore, MIGS devices are typically reserved for mild-to-moderate glaucoma cases.

New World Medical, USA, a company famous for its iconic Ahmed Glaucoma Valve has developed the Ahmed ClearPath device which offers patients another treatment option and surgeons more convenient and efficient tube surgery. This device targets patients with severe or moderate glaucoma.

The ClearPath is the culmination of the efforts of a group of glaucoma surgeons to develop a non-valved glaucoma drainage device to shunt aqueous out of the eye.

FEATURES:

The device is available in two sizes, viz, 350 mm² and 250 mm².

The ClearPath consists of a flexible plate with contour closely conforming to the curvature of the eye.

The suture fixation points for the device are conveniently positioned much anteriorly compared to other devices, enabling ease of fixation.

CLEARANCE FROM FDA:

The device received clearance from FDA earlier this year and the company had a limited launch of the technology.

The limited launch to a small group of surgeons was to receive input and feedback from the surgeons and clinicians on their unmet needs; to assess the device’s safety and efficacy and to know if it makes the surgical procedure much more efficient.

New World Medical has CE mark for the device, but is evaluating commercialization strategies outside the USA.

SURGICAL PROCEDURE:

https://www.newworldmedical.com/Clients/NewWorldMedical/Content/NWMCorp/media/pdf/ClearPath_Surgical_Steps.pdf

Once a conjunctival peritomy and sub-tenon’s pocket are created, the ClearPath is secured to the sclera using the surgeon’s preferred suture material. If the Model 350 is selected, the extraocular muscles will need to be isolated. The body of the plate is placed 8 to 10 mm from the limbus in the superior quadrants, resulting in the anterior edge of the suture arms being placed 6 to 8 mm from the limbus. An anterior bevel is cut on the distal end of the silicone tube, and the tube is then inserted into the anterior chamber using forceps to feed the tube through a scleral tunnel created by a 23-gauge needle. If the tube is inserted into the sulcus, a posterior facing bevel may be used to prevent occlusion by the posterior iris. 

NEW WORLD MEDICAL:

https://www.newworldmedical.com/ClearPath

New World Medical was founded in the early 90s by Dr Abdul Mateen Ahmed and has a humanitarian segment.

The mission is to benefit humanity and stems not only from providing innovative high quality products but also supporting surgeons in medical missions, particularly medical missions outside of US, where the glaucoma treatment or procedures are limited.

The organization helps a lot of non-profit organizations to go out to some of these undeveloped markets.

AMERICAN ACADEMY OF OPHTHALMOLOGY GUIDELINES

The American Academy of Ophthalmology (AAO) released it’s guidelines for management of primary open angle glaucoma (POAG) in the usual “Preferred Practice Pattern (PPP)” style used by the academy. 

According to the AAO, “these documents provide guidance for the pattern of practice, not for the care of a particular individual” and “[these] guidelines are not medical standards to be adhered to in all individual situations”.

The OAG-PPP are probably the best guidelines in terms of organization and presentation of the content. 

At the outset, the “Highlighted findings and recommendations for care” are provided. This summarizes the whole guidelines in the form of a birds-eye-view table.

The “Introduction” provides:

1.      Disease definition: Glaucoma is a "Chronic progressive optic neuropathy in adults in which there is characteristic acquired atrophy of the optic nerve and loss of retinal ganglion cells and their axons. It is associated with an open angle on gonioscopy".

2.      Clinical findings characteristic of POAG:

a.       Evidence of optic disc or retinal nerve fiber layer (RNFL) structural abnormalities.

b.      Reliable and reproducible visual field (VF) abnormality.

c.       Adult onset.

d.      Open angles.

e.       Absence of other known explanations for the damage.

Around 40% of patients with characteristic POAG features do not have elevated IOP.

Severity of glaucoma:

Clinical objectives:

Background: Prevalence of POAG after 69 years of age is more common in Hispanics compared to African-American or Caucasians (Figure1 in the PPP).

High IOP is a risk factor for glaucoma. However, IOP above 21mm Hg has poor predictive value to be utilized as a specific IOP cut-off to screen or diagnose for glaucoma.

Odds of having OAG were 1.9-9.2 fold higher for individuals having 1^st degree relatives (siblings or parents) with OAG.

African-Americans and Hispanics had 3 times higher prevalence of OAG compared to non-Hispanic whites.

Central Corneal Thickness (CCT): “The mean CCT in healthy human eyes varies by ethnoracial characteristics”. No standard nomogram correcting applanation IOP measurements for CCT has yet been validated. “It is important to rely on clinical examination of the optic nerve, imaging of the RNFL and assessment of the VF to diagnose glaucoma”. A thinner central cornea has been reported as an independent risk factor (independent of IOP) associated with POAG.

Ocular perfusion pressure (OPP): It is the difference between blood pressure (at systole or diastole) and the IOP. Low OPP leads to alterations in blood flow at the ONH and contribute to progressive glaucomatous ON damage.

The nocturnal mean arterial pressure, if 10mmHg lower than daytime mean arterial pressure may predict progression of NTG and increased risk of VF loss. Low diastolic perfusion pressure is a risk factor only in those taking treatment for systemic hypertension. It is not known if perfusion pressure is associated with glaucoma because of its individual components (systolic BP, diastolic BP or IOP), a combination of these or interaction between these components.

Type 2 diabetes mellitus is a risk factor due to induced micro vascular changes in the ONH and risk of higher IOP.

Myopia is associated with OAG possibly due to weaker scleral support.

Conditions such as migraine, peripheral vasospasm decrease autoregulation of ONH blood flow. 

[Please see association of glaucoma with Flammer syndrome]:http://ourgsc.blogspot.com/2017/07/guest-author-professor-josef-flammer.html

Systemic hypertension may increase ultrafiltration of aqueous. It may also reduce perfusion pressure in the ONH from sclerotic vessels or induced hypotension from treatment.

Translaminar pressure gradient (pressure difference between IOP and intracranial pressure [ICP]): Glaucoma patients have lower intracranial pressure, while ocular hypertensives have higher ICP relative to normal controls.

Population screening for glaucoma is not cost-effective.

Patient outcome criteria:

1. Preservation of visual function.
2. Maintenance of quality of life.

Diagnosis of OAG is dependent on:

1. History (ocular, race, family, systemic; review of records; medication and allergy histories)
2. Evaluation of visual function (assessed through complaints or specific questionnaires [VFQ-25, Glau-QOL]).
3. Physical examination (VA, pupil, anterior segment, IOP, gonioscopy, ONH & RNFL examination, fundus examination).

Diagnostic testing includes:

1. CCT measurement
2. VF evaluation
3. ONH & RNFL imaging

In Ocular Hypertension Treatment Study and European Glaucoma Prevention Study eyes with CCT less than 555 had higher risk of developing OAG compared to those with CCT of 588 or greater.

Computer-based quantitative imaging of ONH and RNFL is common but “abnormal results from these devices do not always represent disease”.

Non-glaucomatous causes of optic atrophy should be kept in differential diagnosis.
http://ourgsc.blogspot.com/2017/05/optic-atrophy-12.html 

Goals of Management:

1. Control of IOP in target range
2. Stable ON/RNFL status
3. Stable VFs

Initially IOP can be lowered by 25% or more compared to pretreatment levels.

Further lowering of target IOP can be chosen in conditions such as:

1. Patients with severe ON damage
2. Rapidly progressive disease
3. Presence of risk factors such as: family, history, age, disc hemorrhages.

Periodically reassess target IOP.

Choice of therapy:

1. Medical treatment
2. Laser therapy
3. Incisional glaucoma surgery

In pregnancy beta blockers can be used. Avoid prostaglandins due to risk of premature labor. 

Carbonic anhydrase inhibitors and PGAs can be given to breast feeding mothers.

Brimonidine should be avoided due to risk of apnoea in infants.

Trabeculectomy success rates range from 31-88%.

Aqueous shunts (tube shunts, glaucoma drainage devices or setons): Traditionally used to manage medically uncontrolled glaucoma in which trabeculectomy has failed to control IOP or is deemed unlikely to succeed. In the Ahmed Baerveldt Comparison (ABC) and Ahmed Versus Baerveldt (AVB) studies, IOP control was better with BV but serious sight threatening complications were less with AV.

Combined cataract and glaucoma surgeries can be considered in selected cases. However, success rates are better when the 2 procedures are done separately.

Non-penetrating glaucoma surgeries:

1. Deep sclerectomy
2. Viscocanalostomy
3. Canaloplasty

Minimally Invasive Glaucoma Surgery:

1. Ab interno approach
2. Minimal trauma to ocular tissues (especially conjunctiva )
3. Modest IOP reduction

Ab interno trabeculectomy= Trabectome

Trabecular microbypass stent= iStent

Cyclodestructive surgery= Reduces rate of aqueous production. Risk of post-op decrease in VA and sympathetic ophthalmia.

Risk factors for progression:

Uncontrolled IOP, older age, disc hemorrhage, larger C:D ratio or smaller neuroretinal rim area, beta zone parapapillary atrophy, thinner CCT, decreased corneal hysteresis, lower OPP, pseudoexfoliation, poor adherence to treatment.

Appendix:

Quality of ophthalmic care core criteria

International statistical classification of diseases and related health problems (ICD) codes

Literature searches

Suggested reference texts

Related academy materials

References

THE GUIDELINES CAN BE FREELY DOWNLOADED FROM THE FOLLOWING LINK:

https://www.aao.org/preferred-practice-pattern/primary-open-angle-glaucoma-ppp-2015