Review of Ophthalmology Online

Vol. 20, #39   •   Monday, September 14, 2020


In this Issue:


Progression to Late AMD in AREDS 1 and 2

Researchers analyzed associations between the dietary intake of multiple nutrients and risk of progression to late age-related macular degeneration and its subtypes. They also analyzed progression to large drusen and interactions with AMD genotype.

In the post hoc analysis of two controlled clinical trial cohorts—Age-Related Eye Disease Study (AREDS; recruitment 1992 to 1998) and AREDS2 (recruitment 2006 to 2008)—researchers assessed eyes with no late AMD at baseline in AREDS participants (n=4,504) and AREDS2 participants (n=3,738): a total of 14,135 eyes. The mean age was 71 ±6.7 years, and 56.5 percent were female.

Fundus photographs were collected at annual study visits and graded centrally for late AMD. The dietary intake of multiple nutrients was calculated for each participant from food-frequency questionnaires.

Main outcome measures included progression to late AMD, geographic atrophy, neovascular AMD and (separate analyses) large drusen.

Here were some of the findings:
• Over a median follow-up of 10.2 years, of the 14,135 eyes, 32.7 percent progressed to late AMD.
• For nine nutrients (vitamins A, B6 and C; folate, β-carotene, lutein/zeaxanthin, magnesium, copper and alcohol), high intake levels were significantly (p≤0.0005) associated with decreased risk of late AMD.
• For three nutrients (saturated fatty acid, monounsaturated fatty acid and oleic acid) high intake levels were significantly associated with increased risk.
• Similar results were observed for GA.
• Regarding neovascular AMD, nine nutrients were nominally associated with decreased risk (vitamins A and B6; β-carotene, lutein/zeaxanthin, magnesium, copper, docosahexaenoic acid, omega-3 fatty acid and alcohol) and three with increased risk (saturated fatty acid, monounsaturated fatty acid and oleic acid).
• In separate analyses (n=5,399 eyes of 3,164 AREDS participants), 12 nutrients were nominally associated with decreased risk of large drusen.

Researchers concluded that a higher dietary intake of multiple nutrients—including minerals, vitamins and carotenoids—was associated with decreased risk of progression to late AMD. These associations were stronger for GA than for neovascular AMD. The researchers also noted that the same nutrients tended to have protective associations against large drusen development. Furthermore, strong genetic interactions existed for some nutrient-genotype combinations, particularly omega-3 fatty acids and CFH. Researchers suggested that the data may justify further research into underlying mechanisms and randomized trials of supplementation.

SOURCE: Agrón E, Mares J, Clemons TE, et al. Dietary nutrient intake and progression to late age-related macular degeneration in the Age-Related Eye Disease Studies 1 and 2. Ophthalmology 2020; Aug. 25. [Epub ahead of print].


Complimentary CME Education Videos


Primary Deep Sclerectomy in OAG

Investigators reported long-term outcomes of primary deep sclerectomy (DS) in open-angle glaucoma, and identified factors influencing surgical failure and postoperative complications, as part of a retrospective cohort study.

Participants included consecutive OAG patients undergoing primary DS with follow-up ≥one year. Three intraocular pressure success cutoffs were defined: ≤18 mmHg and 20-percent reduction; ≤15 mmHg and 25-percent reduction; and ≤12 mmHg and 30-percent reduction. Cox multivariable regression analysis investigated factors influencing failure and postoperative complications.

The primary outcome was the success rate of DS according to the defined criteria. Secondary outcomes included IOP over time, factors predictive of failure, incidence and predictive factors of serious postoperative complications.

A total of 513 eyes of 409 individuals with a mean age of 70.2 ±9.8 years and follow-up of 84.1 ±41.6 months were included. Here were some of the findings:
• Mean IOP decreased from 23.5 ±7.3 mmHg to 13.3 ±3.9 mmHg at three years; 12.8 ±4.3 mmHg at five years; and 12.4 ±4.3 mmHg at seven years (p<0.001).
• Success rates at these follow-up time points were:
     o for IOP ≤18 mmHg: (three years) 66.3 percent (62.2 to 70.7 percent); (five years) 57.9 percent (53.4 to 62.7 percent); and (seven years) 54 percent (49.4 to 59.1 percent);
     o for IOP ≤15 mmHg: (three years) 44.5 percent (40.3 to 49.1 percent); (five years) 34.6 percent (30.4 to 39.4 percent); and (seven years) 29.8 percent (25.6 to 34.6 percent); and
     o for IOP ≤12 mmHg: (three years) 18.1 percent (15 to 21.9 percent); (five years) 11.9 percent (9.2 to 15.4 percent); and (five years) 10 percent (7.5 to 13.4 percent).
• For all cutoffs, laser goniopuncture (p<0.001), needling (p<0.001) and postoperative anti-glaucoma medications (p<0.001) were associated with increased failure.
• Intraoperative mitomycin C was associated with reduced failure for IOP ≤15 (p=0.006) and IOP ≤12 (p=0.001), whereas higher preoperative IOP (p=0.001) with increased failure for IOP ≤12.
• Serious complications occurred in 49 eyes, with an estimated incidence (CI) of:
     o (one year) 3.5 percent (1.9 to 5.1 percent);
     o (three years) 6 percent (3.9 to 8 percent);
     o (five years) 8.3 percent (5.7 to 11.8 percent); and
     o (seven years) 9.3 percent (6.3 to 12.2 percent).
• Pseudoexfoliation (p=0.04) or pigmentary (p=0.023) glaucoma, poorer preoperative vision (p=0.017), intraoperative macroperforation (p=0.002), avascular blebs (p=0.009), subsequent phacoemulsification (p=0.007) and intraoperative bevacizumab (p=0.004), but not MMC (p=0.79), were associated with increased serious postoperative complications.
• For phakic patients, the estimated incidence (CI) of subsequent phacoemulsification was:
     o (three years) 16.4 percent (12.6 to 20 percent);
     o (five years) 23.6 percent (19.2 to 27.8 percent); and
     o (seven years) 33 percent (27.7 to 38 percent).

Investigators concluded that DS was an effective long-lasting primary surgical procedure for OAG.

SOURCE: Rabiolo A, Leadbetter D, Alaghband P, et al. Primary deep sclerectomy in open-angle glaucoma: Long-term outcomes and risk factors for failure Ophthalmol Glaucoma 2020; Aug 31. [Epub ahead of print].


Complimentary CME Education Videos


Anti-VEGF Agents’ Efficacy in Wet AMD

When initiating anti-vascular endothelial growth factor treatment for individuals with neovascular age-related macular degeneration, knowledge of prognostic factors is important for advising patients and guiding treatment. Scientists hypothesized that eyes with greater fluctuation in retinal thickness over time would have worse outcomes than eyes with less variation. They investigated whether visual and anatomic outcomes in nAMD eyes initiating anti-VEGF treatment were associated with fluctuations in retinal thickness.

In the study using data from the Comparison of Age-Related Macular Degeneration Treatments Trials and the Inhibition of VEGF in Age-Related Choroidal Neovascularization randomized clinical trial, individuals with previously untreated nAMD were included. Data were collected from February 2008 to November 2012, and analyzed from April 2017 to April 2020.

Foveal center point thicknesses (FCPTs) were extracted from 1,165 study eyes from CATT and 566 study eyes from the IVAN trial, excluding those with three measurements or less. The researchers calculated the standard deviation of FCPT for each eye and grouped them by FCPT SD quartile. They quantified the associations of FCPT SD quartile with outcomes at month 24 or the last available visit by linear or logistic regression, adjusting for baseline best-corrected visual acuity, randomized allocations to drug and treatment regimen, BCVA, development of fibrosis and development of macular atrophy.

Of the 1,731 participants, 1,058 (61.1 percent) were female, and the mean age was 78.6 years. The median (interquartile range) FCPT SD was 40.2 (27.1 to 61.2) in the IVAN cohort and 59 (38.3 to 89.4) in the CATT cohort.

Here were some of the findings:
• After adjusting for baseline BCVA and trial allocations, BCVA worsened significantly across the quartiles of FCPT SD; the difference between the first and fourth quartiles was -6.27 Early Treatment Diabetic Retinopathy Study letters (CI, -8.45 to -4.09).
• The risk of developing fibrosis and macular atrophy also increased across FCPT SD quartiles.
• Odds ratios ranged from:
   o 1.40 (CI, 1.03 to 1.91) for quartile two, to 1.95 (CI, 1.42 to 2.68) for quartile four for fibrosis; and
   o from 1.32 (CI, 0.90 to 1.92) for quartile two, to 2.10 (CI, 1.45 to 3.05) for quartile four for macular atrophy.

Scientists determined that greater variation in retinal thickness in eyes with nAMD during treatment with anti-VEGF was associated with worse BCVA, and development of fibrosis and macular atrophy in the post hoc analyses, despite protocol-directed treatment frequency. They advised that practitioners may want to consider variation in retinal thickness when advising patients about their prognosis.

Source: Evans RN, Reeves BC, Maguire MG, et al. Associations of variation in retinal thickness with visual acuity and anatomic outcomes in eyes with neovascular age-related macular degeneration lesions treated with anti-vascular endothelial growth factor agents. JAMA Ophthalmol 2020; Aug 20. [Epub ahead of print].


A Closer Look at Structural Progression in Glaucoma

Researchers evaluated the spatial and temporal relationship between disc hemorrhage and structural progression in individuals with primary open-angle glaucoma in a three-year prospective cohort study. Individuals with POAG and intraocular pressure of ≤18 mmHg on monotherapy with prostaglandin analogs were included.

Researchers took fundus photographs at baseline and every three months for three years. They detected DHs and structural progression independently by flicker chronoscopy, and clock-hour disc locations in the right eye format and colocalization if present. Statistical comparisons were based on mixed-effects models accounting for the correlation between different disc sites within the same eye and between fellow eyes in the same patient.

The main outcome measure included the relationship between DH and structural progression at the same site. Here were some of the findings:
• Among 195 eyes of 115 individuals, DHs appeared in 85 sites in 65 eyes (33.3 percent) and were most frequently at the 7 o'clock disc location (29.4 percent, p<0.0001).
• Structural progression occurred at 63 sites of 52 eyes (26.7 percent), comparably in superior and inferior hemidiscs, which was mainly detected as widening of the retinal nerve fiber layer defects.
• Temporal RNFL defect widening was common, while nasal widening occurred exclusively in the vertical quadrants (p=0.035).
• Of 41 progression sites in eyes with DHs, 28 sites (68.2 percent) had DHs and progression.
• Progression sites with DHs were less common in the superior quadrant than in the inferior and temporal quadrants (p=0.011).
• Eyes with DHs had significantly higher risk of progression than those without DHs (hazard ratio, 3.72; p<0.0001).
• For 63 progression sites, DH recurrence and a greater number of visits with DHs at the progression site were significantly associated with shorter time to progression from baseline (p=0.021, 0.017; respectively), while colocalization of DHs and progression wasn’t.

Researchers reported that the relationship between DH and RNFL defects and the pattern of RNFL defect progression differed by disc location. They found that more frequent DHs at the progression site was a significant factor for shorter time to progression, indicating that DHs may reflect additional vulnerability of structural deterioration at the progression site.

SOURCE: Higashide T, Ohkubo S, Udagawa S, et al. Spatial and temporal relationship between structural progression and disc hemorrhage in glaucoma in a 3-year prospective study. Ophthalmol Glaucoma 2020; Aug 21. [Epub ahead of print].




Industry News

Genentech Initiates Phase III Trial Investigating PDS for DR

Genentech initiated a Phase III clinical trial investigating the Port Delivery System with ranibizumab for people with diabetic retinopathy. PDS is a permanent refillable eye implant, approximately the size of a grain of rice, which continuously delivers a customized formulation of ranibizumab over a period of months. Pavilion, a Phase III, multicenter, randomized study, will evaluate the efficacy, safety and pharmacokinetics of PDS for the treatment of DR in people without diabetic macular edema. The primary endpoint of Pavilion is the percentage of patients who achieve a two-step or greater improvement in DR severity from baseline at week 52, as measured by the Early Treatment Diabetic Retinopathy Study Diabetic Retinopathy Severity Scale. Read more on Pavilion.



Topcon Announces the U.S. Launch of Aladdin-M

Topcon Healthcare launched its new Aladdin-M instrument to the U.S. market. Aladdin-M combines corneal topography, pupillometry and optical biometry to enable objective measurement of corneal curvature, pupil dynamics and axial length metrics. The device provides tools to support myopia management in addition to features for keratoconus screening and contact lens fitting, Topcon says. Learn more.



FDA Approves Drug for Rare Disorder

The U.S. Food and Drug Administration recently approved Genentech's drug Enspryng (satralizumab-mwge) for the treatment of neuromyelitis optica spectrum disorder (NMOSD) in adults with a particular antibody – patients who are anti-aquaporin-4 or AQP4 antibody-positive. NMOSD is a rare autoimmune disease of the central nervous system that mainly affects the optic nerves and spinal cord. Read more.



Zeiss Updates IOLMaster 700 Software

Zeiss says the new software for the IOLMaster 700 (1.90) has enhanced features and connectivity designed to improve cataract surgeons’ workflow efficiency. The update includes central topography, access to surgical planning data on mobile devices with EQ Mobile from ZEISS, and the Barrett True K with Total Keratometry formula. Read more.



FDA Approves Cystadrops for Ocular Manifestations of Cystinosis

Recordati Rare Diseases announced that the FDA has approved Cystadrops (cysteamine ophthalmic solution) 0.37%—a new viscous eye drop solution that depletes corneal cystine crystal deposits in people living with cystinosis, a rare genetic condition that leads to the build-up of cystine crystals throughout the body, causing widespread tissue and organ damage and significant impact on the eyes.  Cystadrops is the first FDA-approved cysteamine drop formulation with q.i.d. dosing, the company says. Read more.



BVI Expands Malosa Single-use Instrument Range

BVI announced the extension of its Malosa range of single-use ophthalmic instruments in the United States. The Malosa portfolio, which now includes specialty instruments for use in corneal refractive surgery, complements the company’s single-use products for cataract, oculoplastic and office-based procedures such as LASIK, PRK and SMILE. Learn more.



Quantel Launches Mosar Imaging System

Quantel Medical launched Mosar, a new optional imaging system, dedicated to the Easyret yellow retinal laser. Mosar is composed of an HD camera, a screen and a computer. Designed to enhance retinal laser treatment procedures and patient follow-up, Quantel says the new imaging system offers a user-friendly software interface. Read more.



Ocular Therapeutix Resolves FDA Warning Letter Related to ReSure Sealant, Announces Third MAC to Establish New Published Physician Fee Schedule for Intracanalicular Insert Administration

Ocular Therapeutix received a letter from the FDA closing out an FDA warning letter received October 18, 2018, concerning ReSure Sealant. The original warning letter was based on the observed inability to conduct a study evaluating endophthalmitis rates following ReSure use in a post-approval Device Exposure Registry study required under 21 CFR 814.82(a)(2) as a condition of a premarket approval application. It was determined that the ability to enroll a study evaluating endophthalmitis rates was prohibitively challenging due to the size of the study, which would have required tens of thousands of patients. The company reached an agreement with the FDA to conduct a retrospective study looking at sites with access to ReSure compared to those without access to ReSure using the Iris Registry data base. Read more.

The company also announced that National Government Services, one of seven Medicare Administrative Contractors, became the third MAC to establish a physician fee schedule for procedure code 0356T for the administration of drug-eluting intracanalicular inserts, including the company’s insert, Dextenza (dexamethasone ophthalmic insert) 0.4 mg, effective July 1. Read more.



AMA Issues CPT Category III Codes for Artificial Iris Implantation

VEO Ophthalmics announced the American Medical Association issued three separate CPT codes for the "insertion of iris prosthesis." The CPT Category III codes, 0616T, 0617T and 0618T, were effective July 1. Earlier this year, the CustomFlex ArtificialIris was approved by the CMS for transitional pass-through payment status, effective January 1. The HCPCS code for the CustomFlex ArtificialIris associated with pass-through payment is C1839: Iris prosthesis. Read more.



Prevent Blindness Launches “Glaucoma Community”

Prevent Blindness and Responsum Health launched The Glaucoma Community, a new platform that can be accessed for free via web browser or mobile app, to educate the public on glaucoma, and offer resources to patients and caregivers. The Glaucoma Community was made possible by a grant from The Allergan Foundation. Special features include: a personalized newsfeed, a community chat, a moderated social wall, automatic translation into seven languages and Patient One-Sheet, which allows patients to collect, maintain and print their key medical information in a secure format. Read more.











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