Review of Ophthalmology Online



Vol. 20, #52   •   Monday, December 14, 2020


In this Issue:


Prediabetes & Structure of the Macula: Northern Finland Birth Cohort

The aim of this study was to evaluate the effect of prediabetes and diabetes on macular thickness and retinal vascular calibers in a population-based cohort (Northern Finland Birth Cohort).

The population of 2,005 individuals was divided into diabetes (n=57), prediabetes (n=1,638) and normal glucose metabolism (NGM) groups (n=310). Researchers measured total thickness of the macula using Cirrus HD-OCT 4000, and they measured central retinal arteriolar equivalent (CRAE) and central retinal venular equivalent (CRVE) calibers from the fundus images. A diagnosis of diabetes and prediabetes was made according to WHO 2006 diagnostic standards.

Here were some of the findings:
• Significant macular thinning was observed in subjects with prediabetes:
   o -2.69 μm (CI, -4.29 to -1.09)(p<0.05) for macular cube average thickness;
   o -0.10 mm3 (CI, -0.16 to -0.04)(p<0.05) for cube volume; and
   o it was greatest in the pericentral area.
• Macular cube average thickness and macular cube volume decreased significantly with worsening glucose metabolism.
• Furthermore, CRAE decreased as two-hour post-load glucose (p<0.001), glucose area under the curve (p<0.019) and Matsuda index (p<0.001) increased.
• In mediation analysis, macular thickness had significant average causal mediation effect on CRVE and CRAE in subjects with prediabetes.

Researchers reported significant thinning of the macula in subjects with prediabetes; the diameter of retinal arteries decreased with impaired glucose metabolism. They noted early and subtle changes, as macular thinning had a significant average causal mediation effect on retinal vessels, supporting the neurodegenerative theory of diabetes-induced changes in the retina.

SOURCE: Huru J, Leiviskä I, Saarela V, et al. Prediabetes influences the structure of the macula: Thinning of the macula in the Northern Finland Birth Cohort. Br J Ophthalmol 2020; Oct 7. [Epub ahead of print].



Seasonal Fluctuation in IOP and RNFL Thinning in POAG

In an observational, retrospective cohort study, investigators assessed seasonal fluctuations in intraocular pressure in normal and primary open-angle glaucoma eyes, and evaluated whether such fluctuations affected retinal nerve fiber layer thinning in POAG patients.

In a normal population undergoing a comprehensive health checkup, POAG patients using only topical medications were enrolled.

Investigators used Kaplan-Meier survival analysis to compare the cumulative incidence probability of RNFL thinning between different seasonal IOP fluctuation groups. They used a Cox proportional hazards model, with adjustments for potential confounding factors, to evaluate the association between seasonal fluctuations in IOP and RNFL thinning. Main outcome measures included the IOP fluctuation rate calculated from winter and summer IOPs, and RNFL thinning as determined by event-based analysis using high-definition optical coherence tomography.

Here were some of the findings:
• A total of 12,686 normal eyes, and 179 eyes of 179 POAG patients showed a significantly higher IOP in winter than in summer (normal, 13.2 ±3 vs. 12.5 ±2.9 mmHg, p<0.001; POAG, 13.1 ±2.7 vs. 11.8 ±2.3 mmHg, p<0.001).
• In POAG patients, the mean age at initial OCT was 55.1 ±11.7 years, and follow-up duration was 98.4 ±26.4 months.
• At first visit, the mean deviation (MD) was -2.2 ±3.4 dB, MD slope was -0.07 ±0.44 dB/year, and RNFL thinning rate was -0.44 ±0.88 μm/year.
• During the study period, 85 eyes (47.5 percent) showed RNFL thinning progression.
• Kaplan-Meier analysis revealed a high seasonal IOP fluctuation rate significantly suppressed RNFL thinning (p<0.05 by log-rank test).
• After adjusting for confounders in the Cox analysis, the seasonal IOP fluctuation rate showed a significantly negative association with RNFL thinning (hazard ratio, 0.98; CI, 0.96 to 0.99; p=0.005).

Investigators found that winter IOP was higher than summer IOP in both normal and POAG eyes. They added that the temporary IOP decline in summer, rather than a constant IOP throughout the year, might help prevent glaucoma progression.

SOURCE: Terauchi R, Ogawa S, Noro T, et al. Seasonal fluctuation in intraocular pressure and retinal nerve fiber layer thinning in primary open-angle glaucoma. Ophthalmol Glaucoma 2020; Nov 23. [Epub ahead of print].



Genetic Risk, Lifestyle & AMD: The EYE-RISK Consortium

Scientists wrote that many risk variants for age-related macular degeneration have been identified, but interpretation is still challenging. They investigated the genetic distribution of AMD-associated risk variants in a large European consortium, calculated attributable and pathway-specific genetic risks and assessed the influence of lifestyle on genetic outcomes, as part of the pooled analysis of cross-sectional data from the E3 consortium.

Participants included 17,174 individuals (ages 45-plus) that took part in six population-based cohort studies, two clinic-based studies and a case-control study.

AMD was diagnosed and graded based on fundus photographs. Scientists harmonized and completed data on genetics, lifestyle and diet when necessary. They calculated minor allele frequencies and population-attributable fraction (PAF) per single nucleotide polymorphism (SNP). They constructed a total genetic risk score (GRS) and pathway-specific risk score (complement, lipid, extra-cellular matrix, other) based on the dosage of SNPs and conditional betas, along with a lifestyle score based on smoking and dietary intake.

Here were some of the findings:
• The risk variants with the largest difference between late AMD cases and controls, and the highest PAFs were located in ARMS2 (rs3750846) and CHF (rs570618 and rs10922109).
• Both risk-increasing and protective variants had the highest PAFs.
• Combining all genetic variants, the total genetic risk score ranged from -3.50 to 4.63; it was normally distributed and increased with AMD severity.
• Of the late AMD cases, 1,581/1,777 (89 percent) had a positive total GRS.
• The complement pathway and ARMS2 were the most prominent genetic pathways contributing to late AMD (positive GRS, 90 percent of late cases), but risk in three pathways was most frequent (35 percent of late cases).
• Lifestyle was a strong determinant of the outcome in each genetic risk category; unfavorable lifestyle increased the risk of late AMD by at least twofold.

Scientists wrote that genetic risk variants contributed to late AMD in most cases but that lifestyle factors had a strong influence on the outcome of genetic risk. As a result, they suggested lifestyle factors should be a strong focus in patient management. Scientists concluded that genetic risks in ARMS2 and the complement pathway were present in the majority of late AMD cases, but were mostly combined with risks in other pathways.

SOURCE: Colijn JM, Meester M, Verzijden T, et al; EYE-RISK Consortium. Genetic risk, lifestyle, and AMD in Europe. The EYE-RISK consortium. Ophthalmology 2020; Nov 27. [Epub ahead of print].



Clinical Efficacy of Atropine in Slowing Myopia Progression

Researchers assessed the clinical efficacy of 0.01% atropine in slowing the progression of myopia in children, and evaluated the influence of the drug on secretion of basal tears and stability of the tear film.

Among 80 children ages 5 to 14 years with myopia, 40 were randomly divided into two groups consisting of those who received spectacles in addition to 0.01% atropine (SA group) and those who received only spectacles (S group). The remaining 40 children who were wearing orthokeratology (OK) lenses for three months were randomly divided into two groups: those who received OK lenses in addition to 0.01% atropine (OKA group); and those who received only OK lenses (OK group). Comprehensive ophthalmologic exams, including a slit-lamp exam, visual acuity testing, autorefraction, tonometry, axial length (AL), corneal topography, Schirmer's test, and tear-film breakup time (TBUT), were performed before treatment and after every three-month treatment.

Here were some of the findings:
• During the follow-up visits, apparently better spherical equivalent control over three, six and 12 months was observed in the SA and OKA groups compared with the S and OK groups.
• The AL over three, six and 12 months was apparently inhibited in the SA and OKA groups compared with the S and OK groups.
• No statistically significant differences in Schirmer's test and TBUT results were observed between the S and SA groups, or between the OK and OKA groups.
• Statistically significant differences were found in TBUT results between the before-treatment and after-three-month treatment period in the OK group (p<0.05, paired T test) and the OKA group (p<0.05, paired T test).

Researchers wrote that 0.01% atropine could effectively control myopia progression and axial elongation regardless of combined treatment with spectacles or OK lenses. They added that 0.01% atropine had no apparent effect on Schirmer's test and TBUT results, although both results tended to reduce after treatment with 0.01% atropine.

SOURCE: Zhao Q, Hao Q. Clinical efficacy of 0.01% atropine in retarding the progression of myopia in children. Int Ophthalmol 2020; Nov 17. [Epub ahead of print].




Complimentary CME Education Videos


Industry News

Janssen Acquires Rights to Novel Gene Therapy for GA

Janssen Pharmaceuticals announced the acquisition of rights to Hemera Biosciences’ investigational gene therapy HMR59, administered as a one-time outpatient intravitreal injection to help preserve vision in patients with geographic atrophy. Financial terms of the transaction weren’t disclosed. The Phase I study of HMR59 for patients with GA is complete. A second Phase I study exploring HMR59 in patients with wet-AMD is conducting follow-up visits to evaluate long-term safety. Read more.



Topcon Announces the U.S. Launch of RDx

Topcon Healthcare launched its new Topcon RDx ocular telehealth software platform in the U.S. market. Topcon RDx is an eye health exam platform that enables practitioners to connect to their offices remotely and conduct comprehensive eye exams in real-time from virtually anywhere, the company says. RDx connects to Topcon's CV-5000S digital phoropter so practitioners can perform fully remote refractions. Read more.






FDA Accepts Eyenovia’s IND for MicroLine

Eyenovia announced the FDA accepted its Investigational New Drug application for MicroLine, a proprietary pilocarpine formulation for the improvement of near vision in patients with presbyopia. The company intends to initiate the Phase III VISION program later this month. Read more.



Research Confirms Presence of SARS-CoV-2 in Ocular Tissue

Eversight announced research findings showing a small, but noteworthy, prevalence of SARS-CoV-2 in ocular tissues from individuals who died from COVID-19. The findings were published in The Ocular Surface. A team of researchers from Eversight, Wayne State University, University of Michigan and Rush University conducted the study in regions heavily impacted by COVID-19. Read more.




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