From the editors of Review of Ophthalmology:
DECEMBER IS SAFE TOYS AND CELEBRATIONS MONTH
In this issue: (click heading to view article)
Exudative AMD Treated with Intravitreal Anti-VEGF Injections: Ten-year Follow-up
Researchers identified the visual acuity outcomes of subjects with age-related macular degeneration treated with intravitreal anti-vascular endothelial growth factor injections over a 10-year period.
The retrospective, cohort study included eyes with exudative AMD that received ≥2 intravitreal anti-VEGF injections and had at least 10 years of follow-up after the initiation of treatment. Snellen visual acuity was recorded at baseline and then annually until the last year of follow-up. Optical coherence tomography data were collected at the time of treatment initiation and at the last exam visit. Researchers performed a subanalysis on individuals who continued to receive anti-VEGF therapy using a modified treat-and-extend protocol vs. those who discontinued treatment for longer than one year.
A total of 130 eyes of 115 individuals met the inclusion criteria. The mean follow-up after treatment initiation was 11.1 ±0.7 years. Eyes received an average of 45.1 ±32.3 intravitreal injections in total, and a mean of five to seven injections per year. Here were some of the findings:
• The baseline mean logMAR visual acuity was 0.61 ±0.5 (Snellen acuity 20/81), and the final mean logMAR visual acuity was 0.88 ±0.7 (20/152, p≤
• A total of 40 eyes received at least one injection every year.
• Eyes receiving at least one injection a year didn’t have a significant change in visual acuity between baseline and final exams—0.47 ±0.4 (20/59 vs. 0.58 ±0.5 [20/76, p=
0.28]), whereas eyes that didn’t receive at least one injection a year saw a significant decline in visual acuity—0.67 ±0.5 (20/94 vs. 1.01 ±0.7 [20/205, p<
Researchers determined that eyes with exudative AMD that received intravitreal injections every year had stable visual acuity over a 10-year period. They added that continuous intravitreal anti-VEGF therapy may stabilize visual acuity for 10 years and potentially longer.
Source: Starr MR, Kung FF, Mejia CA, et al. Ten-year follow-up of patients with exudative age-related macular degeneration treated with intravitreal anti-vascular endothelial growth factor injections. Retina 2019; Nov 13. [Epub ahead of print].
Keratoconus Characteristics Used in Randomized Trials of Surgical Interventions—A Systematic Review
Investigators evaluated descriptions and inclusion criteria of keratoconus used in randomized trials assessing the efficacy of surgical and nonsurgical interventions.
As part of a systematic review, they searched Pre-/Medline and the Cochrane Library from inception until December 2018. Investigators included randomized trials assessing the efficacy of any kind of keratoconus treatment. No language restrictions were imposed. The team analyzed articles against the inclusion criteria, extracted relevant data—including any kind of keratoconus description—and examined the methodological quality. Here were some of the findings:
• Searches retrieved 459 nonduplicate records and included 57 randomized controlled trials investigating nine different surgical interventions with the most used primary outcome measure being maximum keratometry.
• Only 15 studies (26.3 percent) described eligibility parameters regarding keratoconus staging/classification, of which 12 studies used the Amsler-Krumeich classification.
• Eleven studies were published before 1997 (before publication of the Consolidated Standards of Reporting Trials statement), and none of them described the use of a classification.
• From 1997 onward, 15 of 46 studies (32.6 percent) described the incorporation of a classification system (p=0.051).
• The average methodological quality of included trials was modest.
Investigators wrote that the evidence from randomized trials, even after introduction of the Consolidated Standards of Reporting Trials statement, remained ill-formed regarding a careful definition of keratoconus. They wrote, “This is unfortunate because imprecisions regarding the specification of included patients preclude clinicians to assess applicability, that is, the extent to which they can use inferences drawn from study participants regarding efficacy and adverse events in the care of individual patients.”
SOURCE: Baenninger PB, Bodmer NS, Bachmann LM, et al. Keratoconus characteristics used in randomized trials of surgical interventions-a systematic review. Cornea 2019; Nov 13. [Epub ahead of print].
Kalman Filtering Accuracy in Forecasting VF & IOP Trajectory in Ocular Hypertension
Scientists wrote that techniques that properly identify individuals in whom ocular hypertension is likely to progress to open-angle glaucoma can assist clinicians with deciding on the frequency of monitoring and the potential benefit of early treatment. They tested whether Kalman filtering (KF), a machine-learning technique, could accurately forecast mean deviation, pattern standard deviation and intraocular pressure values five years into the future for individuals with OHT.
The cohort study was a secondary analysis of data from individuals with OHT from the Ocular Hypertension Treatment Study, conducted between February 1994 and March 2009. Individuals underwent tonometry and perimetry every six months for up to 15 years. Scientists trained, validated and tested a KF-OHT model to assess how well it could forecast MD, pattern standard deviation and IOP at up to five years, and compared the forecasts with results from the actual trial. They compared the KF for OHT with a previously developed KF for subjects with high-tension glaucoma (KF-HTG) and three traditional forecasting algorithms. The scientists performed statistical analysis for the present study between 2018 and 2019. Main outcomes were prediction error and root-mean-square error at 12, 24, 36, 48 and 60 months for MD, pattern SD and IOP.
Among 1,407 eligible participants (2,806 eyes), 809 (57.5 percent) were female and the mean (SD) age at baseline was 57.5 (9.6) years.
• For 2,124 eyes with sufficient measurements, KF-OHT was able to forecast MD values 60 months into the future within 0.5 dB of the actual value for 696 eyes (32.8 percent), 1 dB for 1,295 eyes (61 percent) and 2.5 dB for 1,980 eyes (93.2 percent).
• Among the five forecasting algorithms tested, KF-OHT achieved the lowest root-mean-square error (1.72 vs. 1.85 to 4.28) for MD values 60 months into the future.
• For eyes that progressed to OAG, KF-OHT and KF-HTG forecast MD values 60 months into the future within 1 dB of the actual value for 30 eyes (68.2 percent; CI, 54.4 to 82 percent) and achieved the lowest root-mean-square error among all models.
Scientists wrote that the findings suggested that machine-learning algorithms such as KF could accurately forecast MD, pattern SD and IOP five years into the future for many individuals with OHT. They added that these algorithms may aid clinicians in managing OHT in patients.
SOURCE: Garcia GP, Lavieri MS, Andrews C, et al. Accuracy of Kalman filtering in forecasting visual field and intraocular pressure trajectory in patients with ocular hypertension. JAMA Ophthalmol 2019; Nov 14. [Epub ahead of print].
Structural OCT Signs of Subclinical Nonexudative Macular NV in Eyes with Large Drusen
Researchers further defined structural optical coherence tomography features making up the "double-layer sign," which is suggestive of subclinical, nonexudative macular neovascularization (NE-MNV) in asymptomatic eyes with age-related macular degeneration.
In the cross-sectional, observational study, participants included individuals with large drusen (>125μm) secondary to AMD in at least one eye.
Participants in a discovery cohort with known NE-MNV identified on OCT angiography (SS-OCTA) and the double-layer sign on structural spectral-domain OCT imaging were used to identify characteristic features of this sign. The features were then assessed by masked grader in an evaluation cohort of AMD eyes with large drusen to determine the predictive values for NE-MNV. Main outcome measures included a description of OCT features associated with an increased risk of NE-MNV, and their diagnostic and predictive performance. Here were some of the findings:
• The discovery cohort of four eyes revealed that, in retinal pigment epithelium elevations with a greatest transverse linear dimension ≥1,000 μm, an irregular RPE layer, height of predominantly <100 μm, and a non-homogenous internal reflectivity were characteristic features of the double-layer sign when NE-MNV was present. Researchers termed these collective features “SIRE”: Shallow, Irregular RPE Elevation.
• Features on OCT images from 233 eyes in the evaluation cohort that were significantly associated with NE-MNV when RPE elevation was >1,000 um in length were: height of the RPE elevation; an overall flat or variable morphology; RPE layer irregularity; and a non-homogeneous reflectivity (all p≥
• A total of 24 eyes (10.3 percent) were identified with a SIRE.
• On SS-OCTA imaging, six of the 233 eyes were found to have definite NE-MNVs, and all graded positively for SIRE (sensitivity=100 percent).
• The absence of SIRE was identified in 209 of 227 eyes without NE-MNV (specificity=92.1 percent).
• The positive predictive value for SIRE was 25 percent, and the negative predictive value was 100 percent.
Researchers found that OCT images that displayed the SIRE sign were at higher risk of having a subclinical NE-MNV. They determined that SIRE could be used as a screening tool on routine structural OCT imaging and that more frequent follow-up and diligent home monitoring were recommended for those with SIRE features.
SOURCE: Narita C, Wu Z, Rosenfeld PJ, et al. Structural OCT signs suggestive of subclinical nonexudative macular neovascularization in eyes with large drusen. Ophthalmology 2019; Nov. 15. [Epub ahead of print].
Aerie to Commence Phase IIb Study in Dry-eye Subjects in Late 2020
Aerie Pharmaceuticals announced the signing of an agreement for the acquisition of Avizorex Pharma, a Spanish ophthalmic pharmaceutical company developing therapeutics for the treatment of dry-eye disease. AVX completed a Phase IIa study in dry-eye subjects earlier this year with its lead product candidate, AVX-012, showing positive results. The active ingredient in AVX-012 is a selective agonist of the TRPM8 ion channel, a cold sensor and osmolarity sensor that regulates ocular surface wetness and blink rate. Aerie says that, by stimulating these processes in a physiological manner, TRPM8 agonists have the potential to restore tear-film stability and reduce discomfort in patients with dry eye. Aerie plans to initiate a larger Phase IIb study of the drug in late 2020. Read more.
CooperVision MiSight 1 Day Contact Lens for Childhood Myopia Coming to U.S. in 2020
CooperVision announced it received FDA approval of its MiSight 1 day contact lens. The daily-wear, single-use contact lens is the first and only FDA-approved product clinically proven to slow the progression of myopia (nearsightedness or short-sightedness) when initially prescribed for children 8 to 12 years old. CooperVision's research into MiSight 1 day's effectiveness was included a prospective, multicenter, double-masked, randomized study that enrolled 144 myopic children ages eight to 12 years from Singapore, Canada, the United Kingdom and Portugal, which accounts for the FDA's approved age range for initial fitting. In the trial, the lens slowed myopia progression by 59 percent as measured by mean cycloplegic spherical equivalent and by 52 percent as measured by mean axial elongation of the eye. MiSight 1 day will launch in the United States as part of a CooperVision myopia management initiative beginning in the spring of 2020. Read more.
ProQR Receives ODD from FDA for QR-1123 for Autosomal Dominant RP
ProQR Therapeutics announced that it received Orphan Drug designation from the FDA for QR-1123 a first-in-class investigational antisense oligonucleotide designed to address the underlying cause of vision loss associated with autosomal dominant retinitis pigmentosa due to the P23H mutation in the rhodopsin (RHO) gene. (ODD provides a special status for investigational drugs being developed for rare diseases.) The therapy aims to inhibit the formation of the mutated toxic version of the rhodopsin protein by specifically binding the mutated RHO mRNA. Aurora, or the PQ-1123-001 trial, is a first-in-human study that will initially include up to 35 adults with adRP due to the P23H mutation in the RHO gene. Read more.
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