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September 1, 2021


The most important ophthalmology research updates, delivered directly to you.
 
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How do misdiagnosed neuro-ophthalmic conditions lead to patient harm?

Ophthalmology

In the words of Hannah Montana, “everybody makes mistakes”. But, how often do these mistakes affect patient care? Using prospective data from three academic neuro-ophthalmology clinics, investigators analyzed 496 subjects to determine how diagnostic errors of neuro-ophthalmology referrals can lead to patient harm. In total, 49% of case referrals were previously misdiagnosed, 26% of these misdiagnosed cases resulted in direct patient harm, and 97% of cases of patient harm could have been avoided with earlier access to neuro-ophthalmology. 12% of cases were inappropriately referred and these were more likely to be misdiagnosed (76% of inappropriate referrals were misdiagnosed vs. 45% of appropriate referrals, P < 0.0001). Diagnostic errors prior to referral were traced back to the physical examination (36%), generation and consideration of differential diagnoses (24%), history taking (24%), and use or interpretation of diagnostic testing (13%). Neuro-ophthalmology input directly impacted patient care in 99% of cases. Given the current shortage of neuro-ophthalmologists, the authors argue for an increased incentive for trainees to pursue neuro-ophthalmology in order to increase access to care and prevent patient harm. 

Mutations in TMEM45A are Associated with Keratoglobus

JAMA Ophthalmology

A truly translational study! 👦🏻➡️🐭 Keratoglobus is a type of corneal ectasia disorder characterized by prominent peripheral thinning of the cornea and globular protrusion. Although associated with connective tissue disorders, isolated keratoglobus has been thought to be inherited in an autosomal recessive pattern. In this case series, Weiner et al. identified that homozygous mutations in TMEM45A were present in 3 unrelated patients with keratoglobus. The authors then performed additional analyses in both humans and mice to confirm the role for this gene. They first confirmed deletion with Sanger sequencing and ruled out mutations in other genes associated with connective tissue disease. Next, they assessed gene expression in the human cornea and found that TMEM45A mRNA expression is 23 times higher in the cornea than in peripheral blood. Finally, they demonstrated that knockout mice deficient in TMEM45A showed thinner stroma than wild-type mice, a finding associated with keratoglobus. This study is a fascinating example of translational research in which patient sequencing inspired laboratory experiments allowing for the direct implication of a gene in corneal pathology. While the sample size of the case series was small, knowledge of this genetic mechanism could enable earlier disease identification and treatment in affected patients.

Steroids for Steven Johnson Syndrome and Toxic Epidermal Necrolysis?

American Journal Ophthalmology

Could a simple but mighty dose of steroids hold the potential to dissipate the ocular mayhem laid by Steven-Johnson Syndrome (SJS) and Toxic Epidermal Necrolysis (TEN)? SJS and TEN are severe hypersensitivity skin reactions with fever, sore throat, cough, and burning eyes for several days. SJS/TEN can lead to eyelid scarring, corneal vascularization, impaired vision and, in severe cases, require prosthetic replacement of the ocular ecosystem. Both researchers and clinicians have sought to locate quick and efficient treatments to avoid further ocular damage. In this study, researchers retrospectively reviewed records of 85 SJS/TEN patients with severe acute ocular disorders and evaluated the treatments and outcomes, such as best corrected visual acuity (BCVA) and ocular complications. Amongst the enrolled patients, 42% received corticosteroid pulse therapy (CPT) within 4 days of disease onset. Of these, 52.8% had an improvement of BCVA, compared to only 14.3% of patients that did not receive CPT (p < 0.001). Although the authors supported their findings with a large sample size, additional studies are needed to validate CPT as the treatment for all acute SJS/TEN patients.

The Potential for GLP-1R Agonists to Prevent Glaucoma

British Journal of Ophthalmology

We don’t suggest eating tide pods, but we might soon be suggesting medications like liraglutide for our patients! IOP reduction has been a critical tenet for managing glaucoma progression, but glaucoma can still worsen even with ‘normal’ IOP’s. New therapies targeting other mechanisms of glaucoma are needed. GLP-1 agonists have been shown to be neuroprotective in mouse models of neurodegenerative diseases and reduced retinal ganglion cell loss in mouse models of ocular hypertension. The authors sought to study if GLP-1R agonist exposure impacts glaucoma risk through an insurance claims database. 1,961 new users of GLP-1 R agonists were matched to 4,371 unexposed controls based on various demographic and clinical information.  New users of GLP-1R agonists were at a significantly decreased risk of developing glaucoma (HR: 0.56, CI: 0.36-0.89), compared to controls. This study supports further investigating GLP-1 agonists for glaucoma prevention and treatment.

Neuro-Ophthalmology

Gene therapy improves visual outcomes in LHON

Journal of Neuro-Ophthalmology

A certain genetically based injection has been a hot topic of discussion lately, and no, it’s not the Covid-19 vaccine. Leber hereditary optic neuropathy (LHON) is a rare maternally inherited mitochondrial disease that can cause severe, bilateral vision loss. Though researchers have identified three point mutations primarily responsible for the disease, therapeutic modalities are poorly characterized. One promising therapy for LHON is a single-time intravitreal injection of lenadogene nolparvovec, a viral vector which encodes the human wild-type mitochondrial protein and has been shown to prevent optic atrophy and vision loss in mouse models. In this randomized, double-masked clinical trial, 76 patients with LHON were recruited and received a single unilateral injection of lenadogene nolparvovec between 2-13 months after the onset of vision loss. Follow-up at the 2-year and 5-year post-therapy mark showed a sustained improvement of best corrected visual acuity in both eyes from baseline, as well as meaningful improvement in vision-related quality of life survey (+7 points). Overall, this study illustrates the efficacy of gene therapy in a devastating disease with pressing unmet therapeutic needs, though continued follow-up is necessary to fully understand the safety profile and longevity of the therapy.

Oculoplastics

Trends in Oculoplastics-Related Emergency Department Visits

Ophthalmic Plastic and Reconstructive Surgery

When the on-call resident goes to the ED to see a new consult, what are they most likely to find? Recent studies analyzing trends in ophthalmic emergency department (ED) visits have found a decrease in the number of patients with ophthalmic complaints presenting to the ED, yet an increase in nonurgent ophthalmic presentations to the ED. This recently published review is the first to describe patterns and trends in oculoplastics-related ED visits in the U.S from 2006 to 2015. An estimated 4.2 million ED visits related to oculoplastics diagnoses were identified. The incidence of all oculoplastics-related diagnoses decreased over time but total inflation-adjusted cost increased over time. Approximately 31% of the visits were considered nonurgent, with less than 5% of patients requiring hospitalization. However, the presence of orbital pathology was more likely to be urgent, require a procedure, and result in hospitalization. Although this study is limited by inaccuracies in ophthalmic coding, the results suggest that there is room to reduce the number of nonurgent ophthalmic visits to the ED, which would have financial benefits for patients.

Question of the Week
A 10-year-old male is referred to the Ophthalmology clinic after demonstrating loss of vision in the left eye during a visual screening test at the pediatrician. On further history the patient describes a blur in the upper left portion of the visual field in the left eye for at least one year, and some “flakiness” in his central vision more recently. He has not had any pain or photopsia and is completely unaffected in the right eye. Exam reveals a visual acuity of 20/15 OD and 20/200 OU, relative afferent pupillary defect in the left eye, and slit lamp exam is normal from exterior to the lens. Dilated fundus exam in the left eye demonstrates pigmented cell and flare in the vitreous, neovascularization of the disc, lipid and edema in the macula, telangiectasia and a “light-bulb” lesion at 4:00 in the peripheral retina, as seen in the image below. 
What is the most likely diagnosis?
a.     Coats disease
b.     Retinoblastoma
c.     Persistent fetal vasculature
d.     Ocular toxocariasis
 
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