Surgeon Experience as a Risk Factor for Short-Term Failure for Ab Interno Gelatin Microstent: A Canadian Multicenter Propensity-Matched Study.

PURPOSE: To compare the efficacy and safety of early versus later ab interno gelatin microstent placement with mitomycin C. DESIGN: Canada-wide, multicenter, retrospective propensity score-matched cohort study. PARTICIPANTS: Two hundred seventy eyes (135 early cases and 135 later cases) with no prior incisional surgery. METHODS: Surgeons' first 20 patients (early cases group), from 6 glaucoma surgeons across 4 Canadian sites, were matched 1:1 to patients with the closest propensity score from the later (21+) patients (later cases group). MAIN OUTCOME MEASURES: Primary outcome was hazard ratio (HR) of failure of the early versus later cases groups, with failure defined as IOP of less than 6 mmHg with more than 2 lines of vision loss or more than 17 mmHg with no medications (complete success) on 2 consecutive visits despite in-clinic maneuvers (including needling) more than 1 month after surgery. Secondary outcomes were HRs for failure, defined as IOP outside the range of 6 to 14 mmHg and 6 to 21 mmHg with and without allowing for medications (qualified success), interventions, complications, and reoperations. RESULTS: Hazard ratio of failure for early versus later cases groups was 1.38 (95% confidence interval [CI], 0.97-1.96) for the IOP range of 6 to 17 mmHg, 1.29 (95% CI, 0.90-1.84) for 6 to 14 mmHg, and 1.48 (95% CI, 1.03-2.13) for 6 to 21 mmHg without medication and 0.95 (95% CI, 0.55-1.64), 0.95 (95% CI, 0.61-1.48), and 0.95 (95% CI, 0.52-1.75) for the same IOP ranges allowing for medications. Needling rates were 43.0% (early cases group) and 41.5% (later cases group). Complication rates after 1 month occurred in 9.6% (early cases group) and 11.1% (later cases group; P = 0.69). Reoperation rates were 14.8% (early cases group) and 8.1% (later cases group; P = 0.08). CONCLUSIONS: There is some evidence for improved success in the later cases group. Similar needling rates, similar complication rates, and a slightly higher reoperation rate were found for the early cases group. The results suggest that this procedure can be adopted by existing surgeons with current training regimens, although they may see an improvement in their success outcomes over time.

Three-Year Findings of the HORIZON Trial: A Schlemm Canal Microstent for Pressure Reduction in Primary Open-Angle Glaucoma and Cataract.

PURPOSE: To report 3-year outcomes of the HORIZON study comparing cataract surgery (CS) with Hydrus Microstent (Ivantis, Inc) implantation versus CS alone. DESIGN: Multicenter randomized clinical trial. PARTICIPANTS: Five hundred fifty-six eyes from 556 patients with cataract and primary open-angle glaucoma (POAG) treated with 1 or more glaucoma medication, washed out diurnal intraocular pressure (IOP) of 22 to 34 mmHg, and no prior incisional glaucoma surgery. METHODS: After phacoemulsification, eyes were randomized 2:1 to receive a Hydrus Microstent or no stent. Follow-up included comprehensive eye examinations through 3 years. MAIN OUTCOME MEASURES: Outcome measures included IOP, medical therapy, reoperation rates, visual acuity, adverse events, and changes in corneal endothelial cell counts. RESULTS: Three hundred sixty-nine eyes were randomized to microstent treatment and 187 to CS only. Preoperative IOP, medication use, washed-out diurnal IOP, and glaucoma severity did not differ between the two treatment groups. At 3 years, IOP was 16.7 ± 3.1 mmHg in the microstent group and 17.0 ± 3.4 mmHg in the CS group (P = 0.85). The number of glaucoma medications was 0.4 ± 0.8 in the microstent group and 0.8 ± 1.0 in the CS group (P < 0.001), and 73% of microstent group eyes were medication free compared with 48% in the CS group (P < 0.001). The microstent group included a higher proportion of eyes with IOP of 18 mmHg or less without medications compared with the CS group (56.2% vs. 34.6%; P < 0.001), as well as IOP reduction of at least 20%, 30%, or 40% compared with CS alone. The cumulative probability of incisional glaucoma surgery was lower in the microstent group (0.6% vs. 3.9%; hazard ratio, 0.156; 95% confidence interval, 0.031-0.773; P = 0.020). No difference was found in postoperative corneal endothelial cell loss between groups. No procedure- or device-related serious adverse events resulting in vision loss occurred in either group. CONCLUSIONS: Combined CS and microstent placement for mild to moderate POAG is safe, more effective in lowering IOP with fewer medications, and less likely to result in further incisional glaucoma filtration surgery than CS alone at 3 years.

Hydrus microstent implantation for surgical management of glaucoma: a review of design, efficacy and safety.

With the advent of microinvasive glaucoma surgery (MIGS), the spectrum of modalities available to manage patients with this chronic and heterogeneous condition has broadened. Despite its novelty however, there has been a rapid evolution in the development of a multitude of devices, each targeting a structure along the aqueous drainage pathway. A growing body of evidence has demonstrated IOP and medication burden reduction, and a more favorable safety profile with MIGS procedures in contrast to traditional incisional surgeries. Among the array of MIGS, the Hydrus® Microstent (Ivantis, Inc., Irvine, CA) is a recent FDA approved device, designed to bypass the trabecular meshwork and provide a scaffold for Schlemm's canal. The objective of this article is to review the Hydrus from conception to clinical use, and present data on its efficacy and safety to date. The available literature has shown promise, however inherent to all novel devices, only long-term monitoring will ensure sustained IOP control and an acceptable safety profile. Surgical advancements in glaucoma have revolutionized the field, and continued research and development will establish these approaches in clinical treatment algorithms.

3D Corneal Shape After Implantation of a Biosynthetic Corneal Stromal Substitute.

PURPOSE: The current and projected shortage of transplantable human donor corneas has prompted the development of long-term alternatives to human donor tissue for corneal replacement. The biosynthetic stromal substitutes (BSS) characterized herein represent a potentially safe alternative to donor organ transplantation for anterior corneal stromal diseases. The goal of this phase 1 safety study was to characterize the three-dimensional (3D) corneal shape of the first 10 human patients implanted with a BSS and assess its stability over time. METHODS: Ten patients underwent anterior lamellar keratoplasty using a biosynthetic corneal stromal implant for either advanced keratoconus or central corneal scarring. Surgeries were performed at Linköping University Hospital, between October and November 2007. Serial corneal topographies were performed on all eyes up to a 4-year follow-up when possible. Three-dimensional shape average maps were constructed for the 10 BSS corneas and for 10 healthy controls. Average 3D shape corneal elevation maps, difference maps, and statistics maps were generated. RESULTS: The biosynthetic stromal substitutes implants remained stably integrated into the host corneas over the 4-year follow-up period, without signs of wound dehiscence or implant extrusion. The biosynthetic stromal substitutes corneas showed steeper surface curvatures and were more irregular than the healthy controls. CONCLUSIONS: Corneal astigmatism and surface steepness were observed 4 years after BSS implantation, while the implants remained stably integrated in the host corneas. Future studies will indicate if biomaterials technology will allow for the optimization of postoperative surface irregularity after anterior stromal replacement, a new window of opportunity that is not available with traditional corneal transplantation techniques.

Corneal Shape, Volume, and Interocular Symmetry: Parameters to Optimize the Design of Biosynthetic Corneal Substitutes.

PURPOSE: To characterize the three-dimensional (3D) shape, volume distribution, and mirror symmetry of the right and left corneas at the scale of a large population, based on the integrated analysis of 3D corneal shape average maps and topography parameters. METHODS: A total of 7670 Orbscan II corneal topographies from 3835 consenting subjects with no history of ocular disease were studied. Average topography maps were created using the right and left corneal topographies of all subjects. To quantify symmetry, left eye topographies were flipped horizontally into "right eye" topographies and statistics maps were generated, including difference and intraclass correlation coefficient (ICC) maps. RESULTS: The standard deviation of the anterior and posterior average elevation maps in the 3-mm radius central zone of the right and left corneas ranged within ± 8 µm and ± 44 µm, respectively. The ICC maps showed almost perfect interocular agreement for anterior elevation, posterior elevation, and pachymetry (all ICCs > 0.96). All studied shape parameters also showed excellent agreement (ICCs ≥ 0.80). Mirror symmetry was not affected by age, sex, or spherical equivalent. We also showed that this horizontal reflection (flip) of the right and left corneal shapes could not be replaced by a simple rotation. CONCLUSIONS: These results indicate that in normal eyes, the anterior elevation, posterior elevation, and pachymetry of the right and left corneas show remarkable symmetry. This comprehensive analysis was achieved with the purpose of guiding the development of future biosynthetic corneal substitutes.

Stable corneal regeneration four years after implantation of a cell-free recombinant human collagen scaffold.

We developed cell-free implants, comprising carbodiimide crosslinked recombinant human collagen (RHC), to enable corneal regeneration by endogenous cell recruitment, to address the worldwide shortage of donor corneas. Patients were grafted with RHC implants. Over four years, the regenerated neo-corneas were stably integrated without rejection, without the long immunosuppression regime needed by donor cornea patients. There was no recruitment of inflammatory dendritic cells into the implant area, whereas, even with immunosuppression, donor cornea recipients showed dendritic cell migration into the central cornea and a rejection episode was observed. Regeneration as evidenced by continued nerve and stromal cell repopulation occurred over the four years to approximate the micro-architecture of healthy corneas. Histopathology of a regenerated, clear cornea from a regrafted patient showed normal corneal architecture. Donor human cornea grafted eyes had abnormally tortuous nerves and stromal cell death was found. Implanted patients had a 4-year average corrected visual acuity of 20/54 and gained more than 5 Snellen lines of vision on an eye chart. The visual acuity can be improved with more robust materials for better shape retention. Nevertheless, these RHC implants can achieve stable regeneration and therefore, represent a potentially safe alternative to donor organ transplantation.

Methodology for the construction and comparison of 3D models of the human cornea.

This paper describes a methodology to build and compare 3D models (or atlases) of the cornea for specific populations. Using topography data of the anterior and posterior corneal surfaces, average and statistical variation maps are computed after registration of individual corneas on a reference sphere. With this methodology, a normal population model is constructed and compared with known eye anatomic data. Comparison of left and right eyes is also performed to see their natural symmetry. Our results demonstrate that spatial normalization is an important step for corneal atlas construction and comparison.