November 3, 2021

The most important ophthalmology research updates, delivered directly to you.
The Lens Artificial Intellegence: This week, we have a special issue on the 6 "rights" for developing robust algorithms with an exclusive author insight from Dr. Al-Aswad, and an overview of applications of AI in diabetic retinopathy, AMD, and IOL calcs.

In this week's issue

  • Genetic variants in the genes CFH, CFI, and C3 were associated with increased risk of late-stage AMD
  • While the overall incidence was not extremely high, anti-VEGF injections were associated with an increase in IOP-related events in patients with retinal vein occlusion
  • Genetic risk for eye size may be unrelated to genetic risk for myopia 

Macular Degeneration: It’s in Your Genes


While CFB, CFI, and CFH may sound like long-lost cousins of C-3PO, they are actually complement related genes that have been linked to age-related macular degeneration (AMD). A European case-control study of 4,740 individuals investigated the association between known genetic AMD risk variants with true AMD diagnosis. This was evaluated via a genotype assay comprised of molecular inversion probes which targeted coding and splice-site regions of 10 AMD-related genes and 3 macular dystrophy genes. The presence of variants in these genes was used to create AMD genetic risk scores. As intended, the assay yielded higher genetic risk scores for patients with late-stage AMD compared with those who had early, intermediate, or no AMD (p<0.001). Rare variants in the CFH (p=0.006), CFI (p=0.005), and C3 (p=0.0003) genes were seen in higher proportions among patients with late-stage AMD than in controls. The results from this assay indicate the practicality of utilizing patients’ genotypes to identify those at risk for developing late-stage AMD. Moreover, sequencing of the complement genes (e.g. CFH, CFI, C3, etc.) can identify rare variant carriers who may be eligible for specific treatment trials.

IOP Elevation Following Intravitreal anti-VEGF Therapy

JAMA Ophthalmology

The pressure is on for anti-VEGF therapy! Intravitreal anti-VEGF injections are a staple for the management of retinal vein occlusion, exudative age-related macular degeneration, diabetic retinopathy, and diabetic macular edema. These relatively safe and highly efficacious injections have been shown to restore vision while reducing the degree of macular edema and neovascularization. One noteworthy risk of anti-VEGF therapy is intraocular pressure (IOP) elevation. Despite their widespread use, few studies have investigated the impact of anti-VEGF injections on IOP in eyes with retinal vein occlusion. Retinal vein occlusion, particularly central retinal vein occlusion, confers an increased risk of glaucoma, and therefore IOP monitoring is of particular importance. In a study of 312 eyes with macular edema treated with aflibercept or bevacizumab in the setting of central retinal vein occlusion (CRVO) or hemi RVO, 25 (8.0%) had an IOP elevation of >10 mmHg over baseline, 5 (1.6%) had an IOP >35 mmHg, and 6 (1.9%) underwent IOP-lowering incisional or laser surgery. At 60-month follow-up, the cumulative incidence of IOP elevation was 0.13 (95% CI 0.08-0.19) for IOP >10 mmHg over baseline and 0.02 (95% CI 0.01-0.06) for IOP > 35 mmHg. These measures did not differ significantly between eyes treated with aflibercept or bevacizumab. This study displays the importance of IOP monitoring in patients with retinal vein occlusion treated with intravitreal anti-VEGF injections.

Environmental effect of fluorinated gases in vitreoretinal surgery

American Journal of Ophthalmology

Have you ever thought about changes you can make to mitigate the effects of climate change? Turns out as an ophthalmologist, you can make a positive contribution. During vitreoretinal (VR) ophthalmic surgery, fluorinated gases such as sulphur hexafluoride (SF6), hexafluoroethane (C2F6) and octafluoropropane (C3F8) are commonly used as intraocular tamponade agents. Unfortunately, these are also among the most potent greenhouse gases. In fact, SF6 has been identified in the Kyoto Protocol as one of six gases which needs to be strictly regulated and limited in its use because of its impact on global warming. In this study, Moussa et al. investigated the direct contribution of these fluorinated gases to carbon emissions. The study was a retrospective, comparative multicentre study that included 4,977 VR operations using fluorinated gases. Intraocular gas masses were then converted to their Global Warming Potential over 100 years and extrapolated to mass of CO2 emissions measured in metric tons. National carbon emission in the UK from VR procedures equalled 928 tonnes and the use of 30ml canisters produced less waste and less carbon emissions than using gas cylinders. The authors conclude that in the future, surgeons and administrative teams should work together to consider the best options for VR surgeries using fluorinated gas, especially from a carbon emission standpoint. With SF6 being the most potent greenhouse gas, VR surgeons can consider using air tamponade more frequently as an alternative when clinically safe to do so. 

Genetic variants for eye size are distinct from myopia


Gee wiz! GWAS study finds genetic variants associated with human eye size. Emmetropization, or visual regulation of eye growth, coordinates the scaling of major ocular components (such as corneal curvature and axial length). A prior study using a chicken model of experimentally induced myopia found that genetic variants regulating eye size were distinct from those conferring susceptibility to myopia (read more here), however the same correlation in humans has not been made. In the current study, researchers hypothesized that the genetic variants that control normal human eye size also do not overlap with those associated with susceptibility to myopia. A genome-wide associated study (GWAS) for corneal curvature (proxy for eye size) was performed in 22,180 emmetropic adults (UK Biobank) followed by creation of a polygenic score of the lead GWAS variants in an independent sample (437 emmetropic, 637 ametropic). Genetic correlation between eye size and refractive error was calculated using linkage disequilibrium score regression. From 32 genetic variants identified in the GWAS for corneal curvature, a polygenic score explained 3.5% (P < 0.001) and 2.0% (P = 0.001) of variance in corneal curvature and axial length, respectively. More strikingly, genetic correlation between eye size and refractive error was close to zero (P = 0.95) supporting the authors’ hypothesis that variants that control eye size are distinct from susceptibility to myopia. Although these findings are limited to individuals of European descent, the large sample size should be considered a strength of the study. GWAS can generate significant amounts of data and help scientists identify genetic variants that could lead to breakthroughs in diagnosing or treating human diseases.

Cornea & Refractive Surgery

Infectious keratitis outcomes during the COVID-19 pandemic


The pandemic has impacted all facets of life, right before our very eyes. This retrospective multicenter study from India aimed to examine the impact of the COVID-19 pandemic on clinical outcomes of infectious keratitis. Data from 258 patients at 6 tertiary eye care hospitals were assessed between March and May 2020, which was the time period in which India maintained strict travel restrictions due to the pandemic. When comparing this data from the pandemic to historical records from 2019, patients during the pandemic presented with greater proportions of severe ulcers (60.0% vs 22.1%; P <.001), total corneal perforations (47.3% vs 11.8%; P <.001), corneal perforation at presentation (18.2% vs 4.4%; P =.002), anatomical failure (23.6% vs 2.2%; P <.001), in addition to more attempts at self-treatment with alternative medicines (36.4% vs 5.1%; P <.001), and fewer anatomical successes (69.1% vs 95.6%; P <.001) or treatment successes (50.9% vs 71.3%; P =.007). The authors hypothesize that the pandemic likely contributed to the delayed presentation for medical care, reduced availability of donor tissues for emergency keratoplasty, and subsequently, an increase in irreversible blindness. 


Rates of Myopia Development in Schoolchildren During the COVID-19 pandemic

JAMA Ophthalmology

Another reason to encourage kids to get off their devices and to go outdoors! As children were transitioned into online courses and spent less time with outdoor activities during the COVID-19 pandemic, there was concern on whether these changes would have a detrimental effect on developing myopia. Hu et al. addressed this with an observational study analyzing data from 2,679 students from grade 2 to grade 3 in either an exposure group (evaluated during the pandemic in 2020) or a non-exposure group (evaluated prior to the pandemic in 2019), and measuring changes in spherical equivalent refraction (SER), axial length (AL) elongation, and myopia incidence at various stages throughout the year. From grade 2 to grade 3, students in the exposure group experienced a 0.36D more myopic shift in SER, greater AL elongation, and 7.9% increase in incidence of myopia compared to the non-exposure group. A key limitation was the retrospective analysis of this data and different time points of comparison. As the shift to increased digital learning may remain in place long after the pandemic, this accelerated incidence of myopia may affect the global burden of myopia development for years to come. 

Question of the Week

A 75 year-old man is referred to the ophthalmologist after awakening with L eye visual field loss and is found to have Humphrey visual field findings given below.
Which is the most likely diagnosis?
A. Arteritic inferior segmental optic neuropathy
B. Non-arteritic inferior segmental optic neuropathy
C. Arteritic superior segmental optic neuropathy
D. Non-arteritic superior segmental optic neuropathy

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