Clinical Investigation of New Glaucoma Procedures

Kateki Vinod; Steven J. Gedde

Disclosures

Curr Opin Ophthalmol. 2017;28(2):187-193. 

In This Article

Targeting the Trabecular Meshwork and Schlemm's Canal

Schlemm's canal-based surgeries facilitate aqueous egress from the anterior chamber into collector channels. An ab-interno approach via a temporal clear corneal incision easily targets the nasal angle, wherein the highest concentration of collector channels is thought to reside.[3] In general, the success of Schlemm's canal-based surgery depends on the patency and functionality of distal outflow pathways, with episcleral venous pressure ultimately limiting the degree of IOP reduction.

Trabectome

Ab-interno trabeculectomy (Trabectome; NeoMedix Inc., Tustin, California, USA) employs a handheld electrode to ablate a strip of trabecular meshwork and inner wall of Schlemm's canal under gonioscopic guidance. A treatment arc of 30–180° can be achieved through a single corneal incision. Trabectome received approval from the United States Food and Drug Administration (FDA) in 2004.

On average, IOP is reduced 30–40% after Trabectome alone or in combination with phacoemulsification and stabilizes in the mid-to-high teens.[4,5] Data are mostly derived from retrospective case series and uncontrolled prospective studies with inherent limitations. A nonrandomized, prospective case series showed that combined Trabectome-phacoemulsification (n = 114) produced a higher success rate (IOP < 21 mmHg and 20% reduction without additional glaucoma surgery) than phacoemulsification alone (n = 145) at 2 years (80 vs. 46%, P < 0.001).[6] Cataract surgery itself has been found to lower IOP,[7,8] but the addition of phacoemulsification to Trabectome (n = 498) was not found to significantly contribute to IOP lowering when compared to Trabectome alone (n = 255) in a retrospective study matching patients by age, race, glaucoma subtype, baseline IOP, and number of medications (P ≥ 0.05).[9] Randomized clinical trials comparing Trabectome alone to Trabectome-phacoemulsification and Trabectome-phacoemulsification to phacoemulsification alone would help validate these findings. A recent meta-analysis[10] of 5091 patients found a mean IOP decrease of 10.5 ± 1.9 mmHg from a baseline of 26.71 ± 1.34 mmHg on 0.99 ± 0.54 fewer glaucoma medications after Trabectome alone. Combined Trabectome-phacoemulsification produced a mean decrease in IOP of 6.24 ± 1.98 mmHg from a baseline of 21 ± 1.31 mmHg using 0.76 ± 0.35 less medications. A higher baseline IOP in the Trabectome alone group likely accounts for its greater mean IOP reduction, given that Trabectome generally does not lower IOP below the mid-teens regardless of whether it is performed alone or in combination with phacoemulsification. Higher success (IOP ≤ 21 mmHg and 20% reduction without additional glaucoma surgery) was observed in the Trabectome-phacoemulsification group (85 ± 7%) than the Trabectome only group (46 ± 34%) at 2 years. High heterogeneity was noted because of the substantial variation in factors such as sample size, baseline IOP, and follow-up duration among studies.

Eyes that demonstrated pronounced intraoperative episcleral venous fluid waves (EVFWs), indicative of sufficient flow through collector channels during Trabectome alone or Trabectome-phacoemulsification, were shown to achieve lower IOP using less medications than eyes without EVFWs in a study of 68 eyes by Fellman et al.[11] (both P = 0.001). Complications after Trabectome tend not to be visually significant, and most commonly include transient hyphema (up to 100%), peripheral anterior synechiae (PAS; 14% of 101 cases), and transient IOP spikes (6% of 1127 cases).[12,13]

iStent

The trabecular microbypass stent (iStent; Glaukos, Laguna Hills, California, USA) is a 1 mm snorkel-shaped device composed of heparin-coated titanium. Angled placement through trabecular meshwork into Schlemm's canal is performed through a corneal incision using a preloaded inserter with the aid of a gonioscopy lens. The iStent was FDA-approved in 2012 for single device implantation in combination with phacoemulsification in patients with mild to moderate OAG and cataract.

The largest clinical trial evaluating single iStent placement randomized OAG patients with cataract to undergo phacoemulsification-iStent (n = 117) or phacoemulsification alone (n = 123) at 29 United States sites.[14,15] A greater proportion of iStent patients than controls achieved IOP ≤ 21 mmHg without medications at 1 year (72 vs. 50%, P < 0.001).[14] Although the study was not statistically powered for a 2-year endpoint, this difference persisted at 2 years (61 vs. 50%, P = 0.036).[15] Medications were added postoperatively to maintain IOP less than 21 mmHg in both groups, and iStent patients required less medications than controls at 1 year (0.2 ± 0.6 medications vs. 0.4 ± 0.7 medications, P = 0.016), but the difference was no longer statistically significant at 2 years. Adverse events were uncommon and occurred at similar rates in both groups. Katz et al.[16] randomized primary open angle glaucoma (POAG) patients to placement of 1 (n = 38), 2 (n = 41), or 3 iStents (n = 40) without concurrent phacoemulsification. At 1 year, success rates (IOP ≤ 18 mmHg and ≥20% reduction from baseline washed-out IOP without supplemental medications or additional glaucoma surgery) were 89.2, 90.2, and 92.1% in the 1-iStent, 2-iStent, and 3-iStent groups, respectively. Mean unmedicated IOP was 15.9 ± 0.9 mmHg in 1-iStent patients, 14.1 ± 1.0 mmHg in 2-iStent patients, and 12.2 ± 1.1 mmHg in 3-iStent patients at 18 months, and mean IOP reduction was significantly greater with each additional iStent placed (P < 0.001). Supplemental medications were needed by 7, 4, and 3 of the 1-iStent, 2-iStent, and 3-iStent patients, respectively, at 18 months. This study evaluated iStent as a standalone procedure without phacoemulsification, and demonstrates the titratable effect of successive iStent placement on IOP. Multiple iStent placement may increase circumferential flow through Schlemm's canal, but the added expense could be prohibitive in clinical practice and cost-effectiveness analyses are therefore needed. Hyphema (2.3–70%) and stent occlusion or malposition (3–17.6%) are the most commonly reported complications associated with iStent.[17]

The second-generation investigational iStent Inject (Glaukos, Laguna Hills, California, USA) allows for perpendicular insertion of two preloaded stents into Schlemm's canal. At 1 year, similar IOP reduction and success rates were found between eyes randomized to insertion of two stents using iStent Inject (n = 94) and those receiving fixed combination two-agent medical therapy (n = 98).[18] A recent retrospective study found a 33 and 35% mean decrease in IOP among patients with POAG (n = 17) and pseudoexfoliation glaucoma (n = 15) 6 months after iStent Inject. Meanwhile, three patients with pigmentary glaucoma experienced IOP spikes (≥30 mmHg) within 1 month of iStent Inject, necessitating trabeculectomy. The retrospective nature and short duration of follow-up in this study limit its generalizability.[19]

Hydrus Microstent

The investigational intracanalicular scaffold (Hydrus Microstent; Ivantis Inc., Irvine, California, USA) is an 8 mm nitinol device that is placed into Schlemm's canal using a preloaded inserter and gonioprism. The microstent dilates and supports three clock hours of Schlemm's canal, promoting circumferential flow into collector channel ostia.

The HYDRUS II trial[20] randomized OAG patients with cataract at seven European sites to receive phacoemulsification-Hydrus (n = 50) or phacoemulsification alone (n = 50). Medication washout was performed at baseline and repeated at 1 and 2 years. At 2 years, the Hydrus group had a lower washed-out diurnal IOP than the control group (16.9 ± 3.3 vs. 19.2 ± 4.7 mmHg, P = 0.0093), and more patients in the Hydrus group had a 20% reduction in washed-out diurnal IOP than in the control group (80 vs. 46%, P = 0.0008). A larger proportion of patients in the Hydrus group did not require medications for IOP control compared with the control group (73 vs. 38%, P = 0.0008). Focal PAS (12%) were the only device-related complication occurring more frequently in the Hydrus group (P = 0.0077). The Hydrus Microstent may have an advantage over single iStent implantation in its ability to access more collector channels, and these devices are being compared in the ongoing HYDRUS III study.

Gonioscopy-assisted Transluminal Trabeculotomy

In gonioscopy-assisted transluminal trabeculotomy (GATT), an illuminated microcatheter (iTrack 250, Ellex, Adelaide, Australia) or suture is passed through a goniotomy to cannulate Schlemm's canal. A 360° ab-interno trabeculotomy is then completed, treating a larger area of trabecular meshwork than traditional trabeculotomy, Trabectome, or iStent. An initial report of eyes with POAG (n = 57) and secondary glaucoma (n = 28) found a mean IOP decrease of 11.1 ± 6.1 mmHg using 1.1 ± 1.8 fewer medications and 19.9 ± 10.2 mmHg on 1.9 ± 2.1 less medications in the two groups, respectively, 1 year after GATT with or without phacoemulsification.[21] Hyphema was present in 30% of patients at 1 week, but all resolved by 1 month. A follow-up report of 14 eyes with primary congenital glaucoma and juvenile OAG demonstrated a reduction in mean IOP and number of medications from 27.3 mmHg and 2.6 at baseline to 14.8 mmHg and 0.86, respectively, at 1 year.[22] Both studies were retrospective and noncomparative, and future randomized clinical trials with extended follow-up would help determine GATT's long-term efficacy and whether scarring of the cleaved trabecular meshwork contributes to late failure.

Canaloplasty

Conceived as an ab-externo procedure, traditional canaloplasty involves scleral flap dissection followed by 360° cannulation of Schlemm's canal with an illuminated microcatheter (iTrack 250, Ellex, Adelaide, Australia) and placement of a tensioning suture. Schlemm's canal is viscodilated to withdraw compressed trabecular meshwork from within collector channel ostia and suture tension is adjusted to maintain trabecular meshwork on stretch. Canaloplasty was FDA approved in 2008 and has since been modified for use as an ab-interno procedure, described anecdotally[23] but not formally studied.

Earlier series found a mean IOP reduction of 29.1–65.9% up to 3 years after ab-externo canaloplasty with or without phacoemulsification.[3] A recent retrospective study of 20 eyes with 5-year follow-up demonstrated a decrease in mean IOP from 25.7 ± 6.6 mmHg using 3.4 ± 0.5 medications at baseline to 14.2 ± 3.4 mmHg using 1.7 ± 1.3 medications at 5 years (both P < 0.001).[24] A majority (13 of 20, 65%) of patients required additional glaucoma surgery. In a randomized trial comparing canaloplasty to trabeculectomy, mean IOP was 2–3 mmHg lower in the trabeculectomy group (n = 32) than the canaloplasty group (n = 30) at all time points, but this difference was not statistically significant (P = 0.56).[25] Late hypotony (IOP < 5 mmHg) occurred more frequently after trabeculectomy (P = 0.03). Canaloplasty does not involve a full-thickness sclerostomy to bypass downstream outflow resistance as does trabeculectomy, so is not expected to produce the same degree of IOP lowering.

Complications after canaloplasty include hyphema (6.1–85.2%) and IOP spikes (≥30 mmHg) secondary to retained viscoelastic (1.6–18.2%), both of which tend to be transient.[26] Suture migration into the anterior chamber and Descemet's membrane detachments have been described. Conjunctival manipulation during canaloplasty can lead to scarring, making future filtering surgery more difficult. Ab-interno suture trabeculotomy remains an option in eyes with persistently elevated postoperative IOP, and was shown to reduce IOP by 41.2% at 1 year when performed an average of 6.1 ± 7.3 months after initial canaloplasty.[27]

Comments

3090D553-9492-4563-8681-AD288FA52ACE

processing....