Review of Ophthalmology Online



Vol. 23, #10  •   Monday, March 14, 2022


In this Issue:





Association of Initial OCTA Vessel Density Loss With Faster VF Loss in Glaucoma

Researchers evaluated the association between the rate of vessel density loss during initial follow-up and the rate of visual field loss during an extended follow-up period in glaucoma suspects and those with primary open-angle glaucoma.

This retrospective cohort study assessed 124 eyes (86 with POAG and 38 suspects) of 82 patients followed up at a tertiary glaucoma center for a mean of four years (CI, 3.9 to 4.1 years) from January 1, 2015, to February 29, 2020. Data analysis for the current study began in March 2021.

The rate of vessel density loss was derived from macular whole-image vessel density values from three optical coherence tomography angiography scans early during the study. The rate of VF loss was calculated from VF mean deviation during the follow-up period after the first OCTA visit. Linear mixed-effects models were used to estimate rates of change.

A total of 124 eyes from 82 patients were assessed. Here are some of the findings:
• The annual rate of vessel density change was -0.80 percent (CI, -0.88 to -0.72 percent) during a mean initial follow-up of 2.1 years (CI, 1.9 to 2.3 years).
• Eyes with annual rates of vessel density loss of -0.75 percent or greater (n=62) were categorized as fast progressors, and eyes with annual rates of less than -0.75 percent (n=62) were categorized as slow progressors.
• The annual rate of VF loss was -0.15 dB (CI, -0.29 to -0.01 dB) for slow OCTA progressors and -0.43 dB (CI, -0.58 to -0.29 dB) for fast OCTA progressors (difference, -0.28 dB; CI, -0.48 to -0.08 dB; p=.006).
• The fast OCTA progressor group was associated with faster overall rate of VF loss in a multivariable model after adjusting to include concurrent VF mean deviation rate (-0.17 dB; CI, -0.33 to -0.01 dB; p=.04).

Researchers wrote that faster vessel density loss during an initial follow-up period was associated with faster concurrent and subsequent rates of visual field loss during an extended period.

SOURCE: Nishida T, Moghimi S, Wu JH, et al. Association of initial optical coherence tomography angiography vessel density loss with faster visual field loss in glaucoma. JAMA Ophthalmol 2022; Feb 24. [Epub ahead of print].





OCT Predictors of Three-year Visual Outcomes for Type 3 MNV

Investigators identifed baseline optical coherence tomography predictors of the three-year visual outcome for type 3 (T3) macular neovascularization secondary to age-related macular degeneration treated by anti-vascular endothelial growth factor therapy.

The retrospective longitudinal study included 40 eyes of 30 patients affected by exudative treatment-naïve T3 MNV. Baseline best-corrected visual acuity and several baseline OCT features were assessed and included in the analysis. Univariate and multivariate analyses served to identify risk factors associated with three-year BCVA.

Main outcome measures included baseline OCT features associated with bad or good visual outcome of type 3 MNV treated by anti-VEGF injections.

Here are some of the findings:
• Mean baseline BCVA of 0.34 ±0.28 logMAR significantly decreased to 0.52 ±0.37 logMAR at the end of three-year follow-up (p=0.002).
• In the univariate analysis, the following baseline features were associated with the three-year BCVA outcome:
   o baseline BCVA (p=0.004);
   o foveal involvement of exudation (p=0.004); and
   o presence of subretinal fluid (SRF)(p=0.004).
• In the multivariate model, the following factors were associated with three-year BCVA outcomes:
   o baseline BCVA (p=0.032);
   o central macular thickness (p=0.036);
   o number of active T3 lesions (p=0.034); and
   o presence of SRF (p=0.008).
• Three-year BCVA was significantly lower in 19 eyes with SRF at baseline (0.69 ±0.42 logMAR) compared with 21 eyes without SRF (0.37 ±0.24 logMAR, p=0.004).

Investigators identified structural OCT features associated with BCVA outcomes after three-year treatment with anti-VEGF injections. They wrote that, unlike some previous findings on neovascular AMD, the presence of SRF at baseline was the most significant independent negative predictor of functional outcomes. They added that their strategy may be used to identify less favorable T3 patterns requiring a more intensive treatment.

SOURCE: Sacconi R, Forte P, Tombolini B, et al. Optical coherence tomography predictors of 3-year visual outcome for type 3 macular neovascularization. Ophthalmol Retina 2022; Feb 25. [Epub ahead of print].


Complimentary CME Education Videos



Utility of Epithelial Thickness Mapping in Refractive Surgery Evaluations

Scientists determined the value of corneal epithelial thickness maps for screening for refractive surgery candidacy, in a single refractive surgical practice.

They evaluated 100 consecutive patients who presented for refractive surgery screening. For each patient, screening was done by performing Scheimpflug tomography, and evaluating clinical data and patient history. A decision was independently made by two masked examiners on eligibility for LASIK, PRK, and SMILE. After examiners were shown patients' epithelial thickness maps derived from optical coherence tomography, they determined the percentage of patient cases that changed regarding surgical candidacy and ranking of surgical procedures from most to least favorable.

Here are some of the findings:
• Candidacy for corneal refractive surgery changed in 16 percent of patients after evaluation of epithelial thickness maps, with 10 percent of patients screened in and 6 percent screened out.
• Chosen surgery changed for 16 percent of patients, and the ranking of surgical procedures from most to least favorable changed for 25 percent of patients.
• Eleven percent of patients gained eligibility for LASIK while 8 percent lost eligibility for LASIK.
• No significant difference was found between the evaluations of the two examiners.

Scientists found that epithelial thickness mapping derived from OCT imaging of the cornea altered candidacy for corneal refractive surgery as well as choice of surgery in a substantial percentage of patients, and was determined to be a valuable tool for screening evaluations. Overall, scientists wrote, the use of epithelial thickness maps resulted in screening for corneal refractive surgery in a slightly larger percentage of patients.

SOURCE: Asroui L, Dupps WJ, Randleman JB. Determining the utility of epithelial thickness mapping in refractive surgery evaluations. Am J Ophthalmol 2022; Mar 2. [Epub ahead of print].


The Phenotypic Course of AMD for ARMS2/HTRA1: The EYE-RISK Consortium

Researchers investigated the phenotypic course and spectrum of age-related macular degeneration for the risk haplotype at ARMS2/HTRA1 in a large European consortium, as part of a pooled analysis of four case-control and six cohort studies

Ten studies from the European Eye Epidemiology consortium provided data on 17,204 individuals ages 55+ years.

Researchers determined AMD features and macular thickness on multimodal images, and harmonized data on genetics and phenotype. They determined risks of AMD features for rs3750486 genotypes at the ARMS2/HTRA1 locus by logistic regression and compared them with a genetic risk score (GRS) of 19 variants at the complement pathway. And they estimated lifetime risk with Kaplan Meier product-limit analyses in prospective population-based cohorts. Main outcome measures included AMD features and stages.

Here are some of the findings:
• Of 2,068 individuals with late AMD, 64.7 percent carried the ARMS2/HTRA1 risk allele.
• For homozygous carriers, the odds ratio of:
   o geographic atrophy was 8.6 (CI, 6.5 to 11.4);
   o choroidal neovascularization was 11.2 (CI, 9.4 to 13.3); and
   o mixed late AMD was 12.2 (CI, 7.3 to 20.6).
• Cumulative lifetime risk of late AMD ranged from 4.4 percent for carriers of the non-risk genotype, to 9.4 percent and 26.8 percent for heterozygous and homozygous carriers, respectively. The latter group received the diagnosis of late AMD 9.6 (CI, 8 to 11.2) years earlier than carriers of the non-risk genotype.
• The risk haplotype wasn’t associated with hard or soft distinct drusen <125 um (OR, 1.2; CI, 0.9 to 1.7), but risks increased significantly for soft indistinct drusen ≥125 um (OR, 2.1; CI, 1.5 to 3; up to OR, 7.2; CI, 3.8 to 13.8) for reticular pseudodrusen.
• Compared with people with a high complement GRS, homozygous carriers of ARMS2/HTRA1 had a significantly higher risk of CNV (OR, 4.1; CI, 3.2 to 5.4), while risks of other characteristics including macular thickness weren’t significantly different.

Researchers found that carriers of the risk haplotype at the ARMS2/HTRA1 locus had a particularly high risk of late AMD at a relatively early age. The data suggested that risk variants at ARMS2/HTRA1 acted as a strong catalyst of progression once early signs were present. Researchers added that the genes’ phenotypic spectrum resembled that of complement genes, only with higher risks of CNV.

SOURCE: Thee EF, Colijn JM, Cougnard-Grégoire A, et al. The phenotypic course of age-related macular degeneration for ARMS2/HTRA1: The EYE-RISK Consortium. Ophthalmology 2022; Feb 28. [Epub ahead of print].




Industry News

Foundation Fighting Blindness and InformedDNA Partner

Foundation Fighting Blindness is partnering with ProQR Therapeutics and InformedDNA to accelerate patient identification and enrollment in clinical research for people with Usher syndrome or non-syndromic retinitis pigmentosa due to mutations in exon 13 of the USH2A gene. The Foundation is using its exclusive My Retina Tracker Registry to identify patients with mutations in USH2A-exon 13 to accelerate identification of candidates for the trials. Read more.

Ray Therapeutics and Forge Biologics Partner

Ray Therapeutics and Forge Biologics, a gene therapy-focused contract development and manufacturing organization, announced a manufacturing partnership to advance Ray Therapeutics’ lead optogenetics gene therapy program, Ray-001, into clinical trials for patients with retinitis pigmentosa. Read more.

New Hires

• EyePoint Pharmaceuticals appointed Isabelle Lefebvre as chief regulatory officer. Previously, Lefebvre was vice-president, head of regulatory science at Hengrui USA, and she spent 10 years at Bausch Health Companies leading the approvals of Lotemax gel and Vyzulta. Read more.
• Okogen appointed Joshua Moriarty as the chief executive officer to replace co-founder Brian Strem, PhD, CEO at Kiora Pharmaceuticals. With 17 years in ophthalmic product development, Moriarty will lead development of OKG-0502 following positive results from the interim analysis of the RUBY Trial. OKG-0502 is a fixed-dose combination of a broad-spectrum antiviral (OKG-0301) and ocular decongestant addressing associated signs and symptoms of adenoviral conjunctivitis. Read more.
• Outlook Therapeutics announced Alicia Tozier was appointed senior vice president, Marketing and Market Access. Over her career, Tozier has led and scaled 60-plus person commercial launch teams and made significant contributions at Genentech, Astellas and Baxter. Read more.

Notal Vision Reports Findings of Home OCT Study

Notal Vision announced that results of the first U.S.-based study with its investigational home-based optical coherence tomography platform reveal over 95 percent agreement when comparing retinal fluid detection capability between Notal OCT Analyzer artificial intelligence and in-office OCT. The findings were published in Ophthalmology Retina. Read more.

Kala Announces Eysuvis Now Covered on UnitedHealthcare Commercial and Cigna Medicare

Kala Pharmaceuticals announced that UnitedHealthcare added Eysuvis (loteprednol etabonate ophthalmic suspension) 0.25% as a covered brand on its commercial formularies. In addition, Cigna Medicare added Eysuvis as a preferred brand, adding an additional 1.9 million Medicare patients. Learn more.

NovaSight Announces Findings from Amblyopia Study

NovaSight announced data from its multicenter randomized controlled trial of CureSight, an eye-tracking based, digital treatment device for amblyopia. The company reports that the digital device treatment was shown to be non-inferior to eye patching for amblyopia treatment in children. Read more.



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