August 11, 2021

The most important ophthalmology research updates, delivered directly to you.
 The Lens Pod: This week, we are joined by Dr. Andrea Tooley, who shares with us what medical students should know before their first oculoplastics clinic and OR. Find the episode on Spotify or our website. Happy listening!

Nearing the Robot Takeover? Using Machine Learning to Predict Intraocular Disease


What if Baymax 🤖 stepped out of Big Hero 6 and into your office? Scientists have recently evaluated the power of machine learning to predict intraocular disease simply by analyzing immune mediators isolated from aqueous humor (AH) samples. In a cross-sectional study of 512 eyes with 17 different diagnoses, concentrations of 28 immune modulators found in the AH were quantified using a cytometric bead array and subsequently ranked according to their predictive power using five machine learning algorithms. Overall, the random forest algorithm proved to be the most accurate in terms of distinguishing between the 17 diseases. The diseases identified most accurately, along with their most predictive immune mediators, were vitreoretinal lymphoma (IL-10, IP-10, angiogenin), acute retinal necrosis (IF-y monokine, IF-y, IP-10), and endophthalmitis (IL-6, GCSF, IL-8). Such technology can advance the accuracy of intraocular disease pathogenesis prediction, potentially leading to earlier diagnoses.

Tragedy in the Port of Beirut: ophthalmologic injury patterns and emergency preparedness

JAMA Ophthalmology

The Port of Beirut explosion on August 4th, 2020 was a catastrophe costing the lives of over 200 people and causing approximately $15 billion worth of property damage. Thousands more were injured, some of whom sustained injuries to the eye and adnexa. In a retrospective medical record review, investigators examined the injury patterns and visual outcomes of 39 blast survivors who presented for ophthalmologic care in the hours to months following the event. The most frequent injuries included ocular surface injury from debris or shattered glass (26 patients, 54.2%), eyelid lacerations (20, 41.6%), orbital fractures (14, 29.2%), open globe injuries (10, 20.8%), eyebrow lacerations (10, 20.8%), and hyphema (blood in the anterior chamber, 9, 18.8%). Seven eyes (14.5%) had a final best-corrected visual acuity of worse than 20/200, four of which sustained open globe injuries with no light perception requiring enucleation or evisceration. Prompt delivery of ophthalmologic care was hindered by patient volume exceeding the capacity of disaster response plans, widespread power outages, and poor internet connectivity. Quality care was made possible by residents and faculty who, despite personal loss and limited resources, responded to the disaster code and established an efficient triage system. Lessons learned from this qualitative and quantitative assessment of medical and logistical problems following the Beirut catastrophe may help healthcare organizations and ophthalmology departments improve their disaster relief plans going forward. 

The original article presents five cases that demonstrate the complexity of problems handled by ophthalmologists in the aftermath of the explosion. These cases may offer an interesting description of ophthalmologic surgery and postoperative care in the emergency setting. Be advised that the article contains graphic images.

Corneal Endothelium as an Indicator of Graves Ophthalmopathy

American Journal of Ophthalmology

A promising index for preventing grave visual outcomes in Graves Ophthalmopathy? It’s all gravy, baby. Grave puns aside, Graves Ophthalmopathy (GO) is the main extrathyroidal manifestation of Graves Disease. It has the potential to significantly impair patient vision and decrease quality of life. The activity of inflammation guides immunosuppressive treatment in Graves patients; however, no reliable marker for disease activity currently exists. In this pilot study, Zhou et al. investigate if damage to the corneal endothelium can act as a quantitative index to reflect GO activity. The cross-sectional study included 128 eyes, 47 with active GO and 81 with inactive GO. Their findings showed that the coefficient variant of cell area in the endothelium (CV, which can be measured in a clinic setting with a non-contact specular microscope) was significantly higher in active GO than in inactive GO (37.0% vs 33.9%, P = .001). However, other parameters measured, including average cell area and endothelial cell density, showed no significant differences between the two groups. Because higher CV implies stressed or damaged endothelium and it was found to be higher in active GO patients, it could be measured routinely to ascertain GO disease progression. Still, the findings of this study must be taken further to assess if the analysis of corneal endothelium in GO patients could lead to improved quality of life and visual outcomes.

Linking miRNA and ubiquitination to retinoblastoma


Small but mighty, microRNAs may hold the power to dictate the course of retinoblastoma progression. Retinoblastoma (RB) is a common intraocular malignancy in children with a complex etiology for disease progression. Many genes and signaling pathways are known to become dysregulated in cancers and researchers sought to further explore pathways involved in RB in this study. They utilized a public dataset to evaluate differentially expressed genes (DEGs) within RB cells followed by protein-protein interaction (PPI) and functional enrichment analyses on these genes to determine the pathways the DEGs were involved in. A total of 258 common DEGs were associated with RB progression and screened out to identify 8 downregulated genes that function in the ubiquitination pathway, with a key finding that a microRNA (miRNA) called miR-548k was involved in RB progression. The ubiquitin-proteasome system plays important roles in cellular homeostasis to regulate protein turnover through a series of enzymatic events. Dysregulation of this system has been implicated in a variety of human diseases including cancers, so these findings align with a potential role in RB. Without proper degradation or turnover of oncogenic proteins, tumor progression or metastasis are more likely. Although the authors validated their findings in a series of follow-up experiments, additional studies are required to pinpoint the exact substrate proteins that become activated due to dysregulation of the ubiquitin-proteasome system. While we’re far from claiming that targeting miR-548k would help prevent RB progression, this study still highlights just how complex disease progression can be. The use of datasets and mining these for bioinformatic analyses has great potential to help answer key questions in ophthalmology research and beyond. 

Cornea & Refractive Surgery

Is limbal stem cell deficiency associated with herpes keratitis?


The new academic year is a time of regrowth, and limbal stem cells can relate. This retrospective case-series study from Massachusetts Eye and Ear aimed to identify characteristics associated with development of limbal stem cell deficiency (LSCD) after herpes keratitis. Limbal stem cells are essential for repopulation of corneal epithelium after an inciting event, such as herpes keratitis. Loss of limbal stem cells can lead to severe epithelial defects, corneal neovascularization, scarring, and inflammation! Records of 626 patients who had a diagnosis of herpes keratitis over a 5-year period were reviewed for evidence of LSCD. Fifty-seven patients had LSCD (9.3%). Keratitis caused by herpes zoster virus [odds ratios (OR), 1.77; 95% confidence interval (CI), 0.97–3.19; P = 0.01], stromal involvement (OR, 2.28; 95% CI, 1.27–4.18; P = 0.02), and the use of topical antihypertensives (OR, 2.28; 95% CI, 1.27–4.18; P = 0.02) were found to be associated with a higher likelihood of developing LSCD. In addition, the final best corrected visual acuity was significantly lower in patients with LSCD compared with those without LSCD. The study concluded that herpes keratitis may be a risk factor for development of limbal stem cell deficiency. Those with a history of herpes keratitis should be monitored for development of LSCD to reduce the risk of ocular surface morbidity.


To cut or not to cut?

BMC Ophthalmology

Promising therapies for children with intermittent exotropia that may help them avoid going under the knife. Intermittent exotropia affects many pediatric patients and is a common cause of childhood strabismus. There is currently a debate on optimal timing for surgical management of these patients, therefore Feng et al. sought to evaluate the efficacy of non-surgical intervention with overminus lenses combined with prism. In this clinical trial, 60 children were recruited and randomly assigned to a control or treatment group prescribed with lenses of -2.50 D and 2 PD base-in prisms. These patients were followed at regular intervals for 12 months to evaluate for refraction changes, ability to control their intermittent exotropia and stereopsis, and decreases in angle of deviation. By the end of the study, the patients in the treatment group had a significant decrease in exodeviation angle, improvement in near stereoacuity, and better control of exotropia. Additionally, there were no significant changes in refractive error providing evidence that overminus lenses do not cause myopia. This study provides a framework for a safe initial therapy for children with intermittent exotropia that may not be candidates for immediate surgical intervention. 

Question of the Week

A 38-year-old female presents to her primary care physician with pain below her right eye for the past 4 days. She states that there has been swelling under her right eye and excessive watering from both eyes during this period. She has no significant medical history and takes no medications. At the physician’s office, her temperature is 98.4 F and her pulse is 87 bpm. Physical exam reveals erythema, warmth, and swelling below the medial canthus of the right eye. It is tender to touch. Upon palpation of the swelling, there is purulent discharge from the lacrimal punctum. Visual acuity is 20/20 bilaterally.
Which of the following is the next best step in management?
A.    Nasolacrimal duct probing
B.    Oral amoxicillin-clavulanate
C.    Lacrimal sac massage
D.    Irrigation of lacrimal canaliculi

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Quiz Answer: B
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