Review of Ophthalmology Online



Vol. 22, #42  •   Monday, October 11, 2021


In this Issue:




Cost-effectiveness Analysis of Minimally Invasive Trabecular Meshwork Stents with Phacoemulsification

Researchers investigated the costs and effects of implanting trabecular meshwork bypass stents during cataract surgery from a societal perspective in the United States.

They used a cost-utility analysis with Markov models and efficacy/safety data from published pivotal or randomized control trials of devices investigated. Patients with mild to moderate primary open-angle glaucoma with or without visually significant cataract ages 65 years and older were included.

Using Markov models, glaucoma progression through four glaucoma states (mild, moderate, advanced and severe/blind) and death was simulated over 35 years. The cohort with cataract entered the model and received cataract surgery with or without device implantation. Researchers included a medication management-only reference group to calculate total costs and outcomes for those without cataract. Intraocular pressure reductions from randomized control trials were converted to glaucoma state transition probabilities using visual field mean deviation decline rates from the Early Manifest Glaucoma Trial. Progressive thinning of the retinal nerve fiber layer on optical coherence tomography imaging related to IOP control warranted further intervention, including adding medication, selective laser trabeculoplasty or incisional glaucoma surgery. Researchers estimated whole costs at Medicare rates and obtained utility values for glaucoma states from previous studies. Incremental costs per quality-adjusted-life-year (QALY) gained were evaluated at a QALY threshold of $50,000. One-way deterministic sensitivity analysis, scenario analyses and probabilistic sensitivity analyses addressed parameter uncertainty and demonstrated model robustness.

Main outcome measures included total costs, QALY and incremental cost-effectiveness ratio (ICER).

Here are some of the findings:
• Over 35 years in the base case, the Hydrus implanted with cataract surgery arm cost $48,025.13 and gained 12.26 QALYs.
• The iStent inject implanted with cataract surgery arm cost $49,599.86 and gained 12.21 QALYs.
• Cataract surgery alone cost $54,409.25 and gained 12.04 QALYs.
• Initial non-surgical management cost $57,931.22 and gained 11.74 QALY.
• The device arms dominated or were cost-effective compared to cataract surgery alone within five years and throughout sensitivity analyses.
• The iStent inject arm was cost-effective in 94.19 percent of iterations in probabilistic sensitivity analyses, while the Hydrus arm was cost-effective in 94.69 percent of iterations.

Researchers reported that implanting either the Hydrus Microstent or iStent inject during cataract surgery is cost-effective at a conservative QALY threshold.

SOURCE: Sood S, Heilenbach N, Sanchez V, et al. Cost-effectiveness analysis of minimally invasive trabecular meshwork stents with phacoemulsification. Ophthalmol Glaucoma 2021; Sep 23. [Epub ahead of print].




Archway Randomized Phase III Trial of the PDS with Ranibizumab for nAMD

Investigators evaluated the safety and efficacy of the Port Delivery System with ranibizumab (PDS) for the treatment of neovascular age-related macular degeneration, as part of a Phase III, open-label, randomized, visual acuity assessor-masked noninferiority (NI) and equivalence trial.

Patients with nAMD diagnosed within nine months of screening previously treated with and responsive to anti-vascular endothelial growth factor therapy were included. They were randomized 3:2 to treatment with the PDS with ranibizumab 100 mg/mL with fixed 24-week refill-exchanges (PDS Q24W) or intravitreal ranibizumab 0.5 mg injections every four weeks (monthly ranibizumab).

The primary endpoint was change in best-corrected visual acuity score from baseline averaged over weeks 36 and 40 (NI margin, -4.5 Early Treatment Diabetic Retinopathy Study letters; equivalence margin, ±4.5 ETDRS letters).

Archway enrolled 418 patients; 251 were randomized to and 248 received treatment with PDS Q24W, and 167 were randomized to and received treatment with monthly ranibizumab. Baseline BCVA was 74.4 (PDS Q24W) and 75.5 (monthly ranibizumab) ETDRS letters (Snellen equivalent 20/32). Adjusted mean (standard error) change in BCVA score from baseline averaged over weeks 36 and 40 was +0.2 (0.5) ETDRS letters in the PDS Q24W arm and +0.5 (0.6) in the monthly ranibizumab arm (difference, -0.3; CI, -1.7 to 1.1). Here are some of the findings:
• The PDS Q24W was noninferior and equivalent to monthly ranibizumab.
• Of 246 PDS-treated patients assessed for supplemental ranibizumab treatment, 242 (98.4 percent) didn’t receive supplemental ranibizumab treatment before the first refill-exchange procedure, including four patients who discontinued treatment before the first refill-exchange procedure.
• Prespecified ocular adverse events of special interest (AESIs) were reported in 47 (19 percent) PDS Q24W and 10 (6 percent) monthly ranibizumab patients.
• Ocular AESIs in PDS-treated patients included four (1.6 percent) endophthalmitis cases, two (0.8 percent) retinal detachments, 13 (5.2 percent) vitreous hemorrhages, six (2.4 percent) conjunctival erosions and five (2 percent) conjunctival retractions.
• Most ocular adverse events in PDS patients occurred within one month of implantation.

Investigators wrote that PDS Q24W demonstrated noninferior and equivalent efficacy to monthly ranibizumab with 98.4 percent of PDS-treated patients not receiving supplemental treatment in the first 24-week interval.

SOURCE: Holekamp NM, Campochiaro PA, Chang M, et al. Archway randomized phase 3 trial of the port delivery system with ranibizumab for neovascular age-related macular degeneration. Ophthalmology 2021; Sep 28. [Epub ahead of print].


Complimentary CME Education Videos


Preoperative Angle Alpha and Angle Kappa Values in Patients Undergoing Multifocal Refractive Lens Surgery

Scientists assessed the preoperative objective angle alpha and angle kappa measurements of patients who decided to undergo multifocal refractive lens surgery based on a subjective positive multifocal contact lens test (MCLT), as part of a retrospective, consecutive case series.

Alpha and kappa angles were measured using the iTrace aberrometer. All patients also underwent a one-week MCLT. Only patients with a positive MCLT underwent surgery. Visual outcome (UCVA) was obtained in the one-year follow-up. Scientists assessed the preoperative distribution of angle values within MCLT positive and negative patient groups.

Two hundred seventeen eyes (111 patients) were included. Mean age was 56.4 years (SD 5.6), and 46.9 percent were female. Here are some of the findings:
• In 71 eyes (38 patients), MCLT was positive.
• Of them, 12 eyes (17 percent) had an angle alpha and angle kappa ≥0.5 mm.
• Of 146 eyes (73 patients) who refrained from surgery due to a negative MCLT, 71 eyes (48.6 percent) had both angles small (<0.5 mm).
• In the one-year follow-up, UCVA improved by 0.68 logMAR (SD 0.51; p<0.001) from baseline.
• Eyes with both small angle alpha and kappa sizes improved by 0.78 logMAR (SD, 0.56), as did eyes with high (≥0.5 mm) angle sizes (0.82 logMAR (SD, 0.53).
• UCVA of eyes (n=24) with high alpha but low kappa sizes improved less (-0.31 logMAR [SD 0.13; p=0.019]).

Scientists determined that four of five patients with a positive MCLT also had correspondingly small angle values. They wrote further that one-half of patients with low preoperative angle values refrained from surgery due to a negative MCLT result, and that one-year visual acuity improvement was substantial and independent of angle sizes.

SOURCE: Baenninger PB, Rinert J, Bachmann LM, et al. Distribution of preoperative angle alpha and angle kappa values in patients undergoing multifocal refractive lens surgery based on a positive contact lens test. Graefes Arch Clin Exp Ophthalmol 2021; Sep 28. [Epub ahead of print.]


Assessing Reading Performance in GA Secondary to AMD with Visual Function and Structural Biomarkers

Researchers prospectively evaluated reading performance in geographic atrophy and assessed its association with established visual function assessments and structural biomarkers.

The noninterventional, prospective natural history study (Directional Spread in Geographic Atrophy) included patients with geographic atrophy secondary to AMD recruited at the University Hospital in Bonn, Germany. Participants were enrolled from June 2013 to June 2016. Analysis began December 2019 and ended January 2021.

Reading acuity and reading speed were assessed using Radner charts. Longitudinal fundus autofluorescence and infrared reflectance images were semi-automatically annotated for geographic atrophy, followed by extraction of shape-descriptive variables. Linear mixed-effects models were applied to investigate the association of the variables with reading performance.

A total of 150 eyes of 85 participants were included in this study (median [IQR] age, 77.9 [72.4 to 82.1] years; 51 women [60 percent]; 34 men [40 percent]). Here are some of the findings:
• Reading performance was impaired, with a median (IQR) monocular reading acuity of 0.9 (0.4 to 1.3) logarithm of the reading acuity determination and a reading speed of 52.8 (zero to 123) words per minute.
• In the multivariable cross-sectional analysis, best-corrected visual acuity, area of geographic atrophy in the central Early Treatment Diabetic Retinopathy Study subfield, classification of non-center vs. center-involving geographic atrophy, and area of geographic atrophy in the inner-right ETDRS subfield showed strongest associations with reading acuity (cross-validated R2 for reading acuity=0.69).
• Regarding reading speed, the most relevant variables were best-corrected visual acuity, low-luminance visual acuity; and area of geographic atrophy in the central ETDRS subfield, in the inner-right ETDRS subfield and in the inner-upper ETDRS subfield (R2 for reading speed=0.67).
• In the longitudinal analysis, a similar prediction accuracy for reading performance was determined (R2 for reading acuity=0.73; R2 for reading speed=0.70).
• Prediction accuracy didn’t improve when follow-up time was added as an independent variable.
• Binocular reading performance didn’t differ from reading performance in the better-seeing eye.

Researchers concluded that the association of reading acuity and speed with visual functional and structural biomarkers supported the validity of reading performance as a meaningful endpoint in clinical trials. These findings suggested that measures in clinical and low-vision care for patients with geographic atrophy should focus primarily on the better-seeing eye.

SOURCE: Künzel SH, Lindner M, Sassen J, et al. Association of reading performance in geographic atrophy secondary to age-related macular degeneration with visual function and structural biomarkers. JAMA Ophthalmol 2021; Sept 30. [Epub ahead of print].




Industry News

Regenxbio Reports Initial Data from Phase II AAVIATE Trial of RGX-314

Regenxbio announced initial data from the ongoing Phase II AAVIATE trial of its gene therapy RGX-314 for the treatment of wet age-related macular degeneration using in-office suprachoroidal delivery, presented at the Retina Society 54th Annual Scientific Meeting. AAVIATE is a multicenter, open-label, randomized, active-controlled, dose-escalation trial that will evaluate the efficacy, safety and tolerability of suprachoroidal delivery of RGX-314 using the SCS Microinjector. Read more.


iCare Announces FDA Approval of Eidon Ultra-widefield Lens Module

The Eidon Ultra-Widefield Lens module from iCare USA received FDA 510(k) approval for distribution in the United States. The ultra-widefield module enables the capture of 120-degree images of the retina in a single shot or up to 200 degrees with its expanded Mosaic function. The company says its image quality enables the detection of small details and signs of pathologies from the center to the periphery. The ultra-widefield lens module can be retrofitted to most Eidon fundus imaging systems. Learn more.

Essilor Introduces Vision-S 700 Refraction Station

Essilor introduced the Vision-S 700 Refraction Station to increase the speed of refraction and “streamline the process with smart tests and algorithms.” The company says it offers a compact design, wider field of vision, and customizable options, among other features. Learn more.

New Testing Module for M&S Clinical Trial Suite

M&S Technologies today announced the “first of six new enhancements” to its Clinical Trial Suite (CTS), the DVA-5000 for Clinical Trial ETDRS and Contrast Sensitivity Function testing. The company says the new dedicated product specifically addresses the needs of glaucoma and retina trial sponsors and researchers. Read more.

Miru 1day Upside Lens Arrives

Menicon America announced the launch of Miru 1day UpSide, a silicone hydrogel daily disposable lens that uses what the company calls “SmartTouch” technology in its packaging. The company says the packaging always presents the lens with the convex side up for ease of handling and to reduce contamination. Read more.

Video Journal Entry Available

The Video Journal of Cataract, Refractive, & Glaucoma Surgery’s third video entry, titled “Celebrating the Producers!” with guest host Robert Osher, MD, is available for viewing. Watch the video.

Aerie to Report AR-1105 Data at ASRS Annual Meeting

Aerie Pharmaceuticals announced that topline results from the AR-1105 (dexamethasone intravitreal implant) Phase II clinical trial in patients with macular edema due to retinal vein occlusion will be presented at the American Society of Retina Specialists annual meeting (October 8 to 12) in San Antonio. Read more.

J&J Vision to Showcase Veritas Vision System at ESCRS Annual Meeting

Johnson & Johnson Vision will showcase its new Veritas Vision System and clinical data at the European Society of Cataract and Refractive Surgeons annual meeting, October 8 to 11. In addition, 29 scientific communications from company-sponsored studies and investigator-initiated studies will be presented, the company says. View the device in person in Amsterdam at the company’s booth #B14. Read more.

Adverum Presents OPTIC Data

Adverum Biotechnologies presented positive long-term data from the OPTIC clinical trial of ADVM-022 single, in-office intravitreal injection gene therapy in patients requiring frequent anti-VEGF injections for neovascular age-related macular degeneration. Safety and efficacy data from patients followed through two years post-injection, presented at the Retina Society’s annual scientific meeting included: >80 percent reduction in annualized anti-VEGF injection frequency in patients who previously required frequent injections; >50 percent of patients (8/152) after median follow-up of 1.7 years remained entirely free of any supplemental anti-VEGF injection; and robust aflibercept expression levels continued to be sustained through two years after a single injection of ADVM-022, the company says. Read more.

4D Molecular Files IND Application for 4D-150

4D Molecular Therapeutics announced the FDA accepted the Investigational New Drug Application for 4D-150 for wet age-related macular degeneration, enabling the initiation of 4D-150 Phase I/II clinical trial sites. 4D-150 is a dual-transgene, intravitreal gene therapy. Read more.








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