Tsontcho Ianchulev

Early postoperative safety and surgical outcomes after implantation of a suprachoroidal micro-stent for the treatment of open-angle glaucoma concomitant with cataract surgery

Purpose To evaluate the safety of a new suprachoroidal device, the Cypass micro‐stent, for the surgical treatment of open‐angle glaucoma (OAG) implanted in conjunction with cataract surgery. Setting Multicenter clinical study. Design Prospective interventional case series. Methods This is an interim report of an ongoing safety study. Patients with OAG glaucoma (Shaffer grade 3 and 4) who were also candidates for cataract surgery in the affected eye had standard phacoemulsification followed by micro‐stent implantation in the supraciliary space. Included were patients with uncontrolled (≥21 mm Hg, Cohort 1) or controlled (<21 mm Hg, Cohort 2) medicated intraocular pressure (IOP) at baseline. Glaucoma medications were discontinued at surgery and resumed at the discretion of each investigator. Measures included adverse events/complications and postoperative changes in IOP or medication. Results The mean baseline medicated IOP was 21.1 mm Hg ± 5.91 (SD); the mean number of IOP‐lowering medications was 2.1 ± 1.1 (N = 184). There were no major events such as retinal or choroidal detachment or endophthalmitis. The most common complications were transient early hypotony (13.8%) and transient IOP increase (10.5%). Uncontrolled patients (n = 57) had a 37% IOP reduction (P<.001), with more than a 50% reduction in glaucoma medications at 6 months (P<.001). Intraocular pressure–controlled patients (n = 41) had a 71.4% reduction in glaucoma medications (P<.001). Conclusion Initial clinical experience with the new micro‐stent showed a low rate of surgical complications with concomitant decreases in IOP and/or glaucoma medications. Financial Disclosure Drs. Hoeh, Ahmed, Swaantje Grisanti, Salvatore Grisanti, Grabner, Nguyen, Rau, and Yoo are clinical investigators for Transcend Medical; Dr. Ahmed is a consultant to Transcend Medical; Dr. Ianchulev is an employee of Transcend Medical.

Intraoperative Refractive Biometry for Predicting Intraocular Lens Power Calculation after Prior Myopic Refractive Surgery

PURPOSE To evaluate a new method of intraoperative refractive biometry (IRB) for intraocular lens (IOL) power calculation in eyes undergoing cataract surgery after prior myopic LASIK or photorefractive keratectomy. DESIGN Retrospective consecutive cases series. PARTICIPANTS We included 215 patients undergoing cataract surgery with a history of myopic LASIK or photorefractive keratectomy. METHODS Patients underwent IRB for IOL power estimation. The Optiwave Refractive Analysis (ORA) System wavefront aberrometer was used to obtain aphakic refractive measurements intraoperatively and then calculate the IOL power with a modified vergence formula obtained before refractive surgery. Comparative effectiveness analysis was done for IRB predictive accuracy of IOL power determination against 3 conventional clinical practice methods: surgeon best preoperative choice (determined by the surgeon using all available clinical data), the Haigis L, and the Shammas IOL formulas. MAIN OUTCOME MEASURES Median absolute error of prediction and percentage of eyes within ±0.50 diopters (D) and ±1.00 D of refractive prediction error. RESULTS In 246 eyes (215 first eyes and 31 second eyes) IRB using ORA achieved the greatest predictive accuracy (P < 0.0001), with a median absolute error of 0.35 D and mean absolute error of 0.42 D. Sixty-seven percent of eyes were within ±0.5 D and 94% were within ±1.0 D of the IRBs predicted outcome. This was significantly more accurate than the other preoperative methods: Median absolute error was 0.6, 0.53, and 0.51 D for surgeon best choice, Haigis L method, and Shammas method, respectively. CONCLUSIONS The IOL power estimation in challenging eyes with prior LASIK/photorefractive keratectomy was most accurately predicted by IRB/ORA.

Initial Clinical Experience With the CyPass Micro-Stent: Safety and Surgical Outcomes of a Novel Supraciliary Microstent.

Purpose:To evaluate safety and clinical outcomes of a novel supraciliary device, the CyPass Micro-Stent, for surgical treatment of open-angle glaucoma when implanted in conjunction with cataract surgery. Patients and Methods:Subjects (n=142) with open-angle glaucoma and cataract underwent combined phacoemulsification, with intraocular lens insertion, and microstent implantation into the supraciliary space of study eyes (n=167). Two analysis cohorts were prespecified based upon medicated baseline intraocular pressure (IOP): ≥21 mm Hg (cohort 1, n=65) or <21 mm Hg (cohort 2, n=102). Glaucoma medications were discontinued or tapered at surgery, and restarted at investigator discretion. The main postoperative outcome measures were adverse events, IOP changes, and number of IOP-lowering medications. Results:Mean±SD follow-up was 294±121 days. No major intraoperative or postoperative complications occurred. Preoperative baseline mean IOP was 20.2±6.0 mm Hg and mean number of IOP-lowering medications was 2.0±1.1. Cohort 1 showed a 35% decrease in mean IOP and a 49% reduction in mean glaucoma medication usage; cohort 2 demonstrated a 75% reduction in mean medication usage while maintaining mean IOP<21 mm Hg. For all eyes, mean IOP at 12 months was 15.9±3.1 mm Hg (14% reduction from baseline). Early and late postoperative IOP elevation occurred in 1.2% and 1.8% of eyes, respectively. Two subjects developed mild transient hyphema, and none exhibited prolonged inflammation, persistent hypotony, or hypotony maculopathy. Conclusions:CyPass Micro-Stent implantation, combined with cataract surgery, resulted in minimal complications and reduced IOP and IOP-lowering medication use at 12 months postoperatively.

Optical coherence tomography of the suprachoroid after CyPass Micro-Stent implantation for the treatment of open-angle glaucoma

Background/Aims To evaluate the supraciliary space (SCS) with anterior segment optical coherence tomography (OCT) imaging after CyPass Micro-Stent implantation. Methods The SCS was imaged with OCT after microstent implantation at 1, 6 months, and 1 year. Images were graded on a scale of 0–4 for morphological features indicative of fluid presence within, or drainage through, the SCS. Results 35 patients underwent ab-interno microstent implantation. Mean age was 68.6±10.2 years. Baseline mean intraocular pressure (IOP) was 21.9±6.1 mm Hg on average of 3.0 topical medications. At 1 month, the fluid space grade was ≥1 for 96% (24/25) of patients for tenting, 79% (15/19) for fluid posterior to the microstent, and 89% (8/9) for fluid surrounding the microstent. The mean (composite) score for all features was 2.5±0.99. The majority of patients maintained aqueous fluid through 12 months. Conclusions OCT imaging provides adequate visualisation of the angle, the SCS and aqueous fluid drainage after implantation of a suprachoroidal microstent into the SCS.

Office-Based Cataract Surgery: Population Health Outcomes Study of More than 21 000 Cases in the United States.

PURPOSE To identify safety and effectiveness outcomes of office-based cataract surgery. Each year, approximately 3.7 million cataract surgeries in the United States are performed in Ambulatory Surgery Center (ASC) and Hospital Outpatient Department (HOPD) locations. Medicare in July 2015 published a solicitation for expert opinion on reimbursing office-based cataract surgery. DESIGN Large-scale, retrospective, consecutive case series of cataract surgeries performed in Minor Procedure Rooms (MPRs) of a large US integrated healthcare center. PARTICIPANTS More than 13 500 patients undergoing elective office-based cataract surgery. METHODS Phacoemulsification cataract surgery performed in MPRs of Kaiser Permanente Colorado from 2011 to 2014. MAIN OUTCOME MEASURES Postoperative visual acuity and intraoperative and postoperative adverse events (AEs). RESULTS Office-based cataract surgery was completed in 21 501 eyes (13 507 patients, age 72.6±9.6 years). Phacoemulsification was performed in 99.9% of cases, and manual extracapsular extraction was performed in 0.1% of cases. Systemic comorbidities included hypertension (53.5%), diabetes (22.3%), and chronic obstructive pulmonary disease (9.4%). Postoperative mean best-corrected visual acuity measured 0.14±0.26 logarithm of the minimum angle of resolution units. Intraoperative ocular AEs included 119 (0.55%) cases of capsular tear and 73 (0.34%) cases of vitreous loss. Postoperative AEs included iritis (n = 330, 1.53%), corneal edema (n = 110, 0.53%), and retinal tear or detachment (n = 30, 0.14%). No endophthalmitis was reported. Second surgeries were performed in 0.70% of treated eyes within 6 months. There were no life- or vision-threatening intraoperative or perioperative AEs. CONCLUSIONS This is the largest US study to investigate the safety and effectiveness of office-based cataract surgery performed in MPRs. Office-based efficacy outcomes were consistently excellent, with a safety profile expected of minimally invasive cataract procedures performed in ASCs and HOPDs.

Wearable technology with head-mounted displays and visual function.

Letters RESEARCH LETTER Wearable Technology With Head-Mounted Displays and Visual Function Interest in wearable head-mounted display systems for gen- eral consumers is increasing, with multiple models in production. 1 However, their effect on vision is largely un- known. Peripheral visual field is a main component of vision and essential for daily activities such as driving, pedestrian safety, and sports. Conventional spectacle frames can reduce visual field, sometimes causing absolute scotomas (blind spots), 2 and head- mounted devices have even more pronounced frames. To quantify their effect on visual function, we compared perfor- mance on perimetric visual field tests with a head-mounted device vs regular eyewear. Methods | Three healthy emmetropic or refractively corrected individuals with 20/20 best-corrected visual acuity and nor- mal baseline visual fields were tested in April 2014. Partici- pants used a wearable device (Google Glass, Google Inc), fol- lowing manufacturer’s instructions, for a 60-minute acclimation period. Participants required minor adjustments to optimize screen visibility. To assess obstruction potential, the display prism’s position relative to the right eye pupillary axis was graded as (1) over central pupillary axis; (2) above cen- tral pupillary axis but inferior to superior limbus; or (3) above superior limbus. Immediately thereafter, participants underwent 30-2 and 60-4 threshold perimetric (visual field) testing with the Hum- phrey Visual Field Analyzer II-750i (Carl Zeiss Meditec). Test- ing was performed first with the device (with software deac- tivated to avoid distractions), followed by a control frame of similar color and temple width. The University of California, San Francisco, determined the study was exempt from insti- tutional review board review. To assess how the devices are worn by general consum- ers, photographs of people wearing the product and facing the camera, obtained from an Internet search conducted on May 1, 2014, were analyzed. 3 The image search included the term Google Glass. The full output of images was reviewed, includ- ing images posted by companies and individuals. Photo- graphs were assessed for prism position relative to the pupil with the grading system described above. Results | Figure 1 shows the baseline characteristics of partici- pants. Visual field testing demonstrated significant scotomas in all 3 participants while wearing the device (Figure 2; note variations in wearing and head position). In all 3 cases, more than 10° of visual field in the horizontal axis were subtended. Scotoma was absent with control perimetry testing with the regular frame. For the image analysis, 311 images were found, with 132 eli- gible for evaluation. The prism covered the pupillary axis in 29.5%, covered the eye but not the axis in 29.5%, and was su- perior to the limbus in 41%. Therefore, 59% had the prism in a position likely to interfere with vision. Discussion | To our knowledge, this is the first evaluation of the effect of wearable electronics with head-mounted display on vision. The device created a clinically meaningful visual field obstruction in the upper right quadrant. Defects were in- duced by the frame hardware design only and were not re- lated to a distracting effect of software-related interference. Image analysis further demonstrated that many people wear the device near or overlapping their pupillary axis, which may induce scotomas and interfere with daily function. This study is limited by the small number of participants, who may not be representative of all users. Even though the scotomas were easily identifiable, a larger sample is needed to identify factors that influence scotoma size and depth. The Figure 1. Baseline Characteristics of Participants Age, y Participant 1 Participant 2 Participant 3 Sex Male Male Male Race White Pacific Islander Asian Refraction oculus dexter (OD) a Plano Plano Best corrected visual acuity OD a Prism placed over the central pupillary axis Prism cleared the central pupillary axis but was inferior to the superior limbus Prism placed over the central pupillary axis Pupillary distance, mm Wearable device prism position a jama.com jamanetwork/2014/jama/05nov2014/jld140032 Indicates the right eye. JAMA November 5, 2014 Volume 312, Number 17 PAGE: right 1 SESS: 24 OUTPUT: Oct 17 11:34 2014

Effectiveness of Intraocular Pressure–Lowering Medication Determined by Washout

IMPORTANCE While medication efficacy is well documented in clinical trials, less is known of medication effectiveness in real-world clinical settings. OBJECTIVE To assess the effectiveness of intraocular pressure (IOP)-lowering medications in patients with open-angle glaucoma. DESIGN, SETTING, AND PARTICIPANTS Prospective, multicenter, interventional cohort from the prerandomization phase of a randomized clinical trial at multiple ophthalmology clinics. A total of 603 patients (603 eyes) with primary open-angle glaucoma who were using up to 3 glaucoma medications were included. INTERVENTIONS One IOP measurement was made while the patient was using his or her usual medications to lower IOP (ON IOP). Eligible participants underwent washout of all IOP-lowering drops, and the diurnal IOP was measured 2 to 4 weeks later (OFF IOP). MAIN OUTCOMES AND MEASURES Difference between OFF IOP and ON IOP. The hypothesis was formulated after data collection. RESULTS The mean (SD) ON IOPs for participants using 0 (n = 102), 1 (n = 272), 2 (n = 147), or 3 (n = 82) medications were 24.2 (3.2), 17.5 (3.2), 17.2 (3.1), and 17.2 (3.1) mm Hg, respectively. Patients not using medication had a mean (SD) IOP decrease of 0.2 (2.8) mm Hg at the OFF visit. Patients using 1, 2, and 3 medications had mean (SD) IOP increases of 5.4 (3.0), 6.9 (3.3), and 9.0 (3.8) mm Hg, respectively, at the OFF visit. The percentages of patients with less than a 25% increase in IOP were 38%, 21%, and 13% for those using 1, 2, and 3 medications, respectively. CONCLUSIONS AND RELEVANCE Discontinuation of 1, 2, and 3 medications was associated with a clinically significant increase in IOP, although with smaller effects for the second and third medications compared with the first medication. A substantial proportion of patients showed only small changes in IOP after medication washout, suggesting either that they were not using the medication effectively or that the medication itself, although used properly, was not lowering the IOP. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT01085357.

Suprachoroidal Space as a Therapeutic Target

The uveoscleral route of aqueous humor outflow has been less well characterized than the trabecular route. The two routes differ physiologically in many respects. Whereas trabecular outflow is dependent on intraocular pressure (IOP), uveoscleral outflow is mostly driven by the higher hydrostatic pressure difference in the anterior chamber relative to the suprachoroidal space (SCS). Outflow through the two routes is also differentially responsive to pharmacological interventions intended to manipulate IOP. For example, prostaglandin-based therapies target the uveoscleral route but have little effect on trabecular outflow. Injection of drugs into the SCS is being investigated as a means of delivery of small molecules and potentially sustained-release formulations of large biological molecules to the back of the eye. The uveoscleral pathway is also being increasingly targeted by diverse surgical approaches, with the potential to avoid some of the more serious complications associated with trabecular surgical interventions.

The CyPass Suprachoroidal Micro-Stent

The CyPass Micro-Stent (Transcend Medical, Menlo Park, CA) is a fenestrated device that is implanted in the supraciliary space to provide a permanent conduit for uveoscleral outflow of aqueous humor from the anterior chamber in patients with glaucoma. Implantation is achieved with a blebless, minimally invasive clear cornea incision that spares the conjunctiva and the sclera and which can be performed with or without the use of surgical intraoperative gonioscopy. By exploiting the negative pressure gradient between the suprachoroidal space and the anterior chamber, the successfully positioned micro-stent facilitates aqueous outflow and thereby lowers IOP and reduces the patient’s need for IOP-lowering medications. Clinical experience to date indicates a good safety profile and prolonged efficacy for the micro-stent when used either as a stand-alone treatment for open-angle glaucoma or in combination with phacoemulsification surgery in glaucomatous patients undergoing cataract removal.

Single vs Multiple Intraocular Pressure Measurements in Glaucoma Surgical Trials

IMPORTANCE Little is known about the necessity of multiple same-day intraocular pressure (IOP) measurements in describing the effect of IOP-lowering surgical procedures, and such evidence could affect surgical trial recruitment and retention of participants. OBJECTIVE To determine whether a single IOP measurement might adequately approximate the mean of several measurements in glaucoma surgical trials. DESIGN, SETTING, AND PARTICIPANTS A prospective, multicenter, interventional cohort from the prerandomization phase of a randomized clinical trial evaluating use of a supraciliary implant for treatment of IOP was conducted at multiple ophthalmology clinics. A total of 609 patients (609 eyes) with primary open-angle glaucoma and cataract were included. INTERVENTIONS One IOP measurement was made while patients were receiving their usual medications to lower IOP, and 3 IOP measurements were made at 8 am, 12 pm, and 4 pm after patients underwent washout of all IOP-lowering eyedrops. MAIN OUTCOMES AND MEASURES The proportion of eyes in which the increase in IOP after washout, using the mean of the 3 measurements, differed by more than 0.5, 1.0, 1.5, or 2.0 mm Hg from the increase in IOP after washout using only 1 of the postwashout measurements. A proportion of 10% or less at the 1.5-mm Hg cutoff was considered clinically acceptable. The hypothesis was formulated after data collection but before the data were examined. RESULTS The mean (SD) IOP before washout was 18.5 (4.0) mm Hg. The mean increase in IOP after washout, using the mean of the 3 measurements, was 5.3 (4.2) mm Hg. The percentage of eyes in which the increase in IOP using a single postwashout IOP differed from the increase in IOP using the mean of 3 measurements by more than 1.5 mm Hg was 35.1%, 25.6%, 34.2%, 30.0%, and 31.4% when the single measurement was made at 8 am, 12 pm, 4 pm, a randomly chosen single measure of those 3 times, and the time closest to that of the prewashout IOP, respectively. By logistic regression, the 12 pm postwashout IOP had the lowest proportion of eyes differing from the mean (P < .001) and thus most closely approximated the mean diurnal IOP. CONCLUSIONS AND RELEVANCE Although eliminating multiple IOP measurements would simplify the conduct of surgical trials in glaucoma, our data show that using a single IOP measurement after washout does not adequately approximate the mean of multiple IOP measurements.