August 18, 2021

The most important ophthalmology research updates, delivered directly to you.
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The Lens Pod: This week, we speak with Dr. Ben Young, host of the Eyes For Ears Podcast, who shares with us what medical students should know before their first retina clinic and OR. Find the episode on Spotify, Apple Podcasts, or our website. Happy listening!

VEGF Inhibitor Aflibercept in Non-Proliferative Diabetic Retinopathy

JAMA Ophthalmology

VEGF inhibitors are the gift that keeps on giving! The natural course of diabetic retinopathy can lead to devastating visual consequences, as vascular damage gives way to neovascularization in the proliferative phase and central macular edema. In this phase 3 double-blind randomized clinical trial, researchers assessed the efficacy of VEGF-inhibitor aflibercept in moderate to severe non-proliferative diabetic retinopathy by comparing aflibercept with placebo, with two treatment arms and one control arm. In one treatment arm, patients received regular dosing throughout the duration of the study, and in the other, patients initially received regular dosing, but were switched to receive PRN dosing after week 52 (PRN if the investigator decided the Diabetic Retinopathy Severity Scale (DRSS) level was worse than 35). In the combined treatment arms, the proportion of eyes with a 2-step or greater improvement in DRSS was significantly higher (157 of 269 eyes, 58.4%) than in the control arm (8 of 133 eyes, 6.0%) (95% CI 45.2-59.5%). The study also demonstrated efficacy of aflibercept in secondary outcomes: treatment arms had a lower proportion of eyes that developed vision threatening complications at week 52 and a lower proportion of eyes with a 2-step or greater worsening from baseline at week 52 and week 100. Importantly, benefits of treatment began to wane when patients were moved from regular dosing to PRN dosing, as the percent of patients with a 2-step or greater improvement decreased from 79.9% at 52 weeks to 50% at 100 weeks, compared with maintained improvement in the continued dosing arm (65.2% at 52 weeks and 62.2% at 100 weeks). This large, international, multi-center study included well-matched patients to assess treatment of non-proliferative diabetic retinopathy and fills an important gap in care for patients with diabetic retinopathy who have not yet progressed to proliferative retinopathy/central macular edema. 

Long-Term Outcomes for Bevacizumab Versus Dexamethasone Injections for Diabetic Macular Edema

British Journal of Ophthalmology

Clinical trials are great at determining which treatment option is best, but what happens to those patients after they return to their doctor for standard care? Anti-VEGF agents have become one of the tenets of care in the treatment of diabetic macular edema. One prior trial, the BEVORDEX trial, aimed to analyze whether intravitreal dexamethasone implant (DEX-implant) vs. intravitreal bevacizumab injections were more efficacious in treating diabetic macular edema. The authors in this study sought to see how enrollees in this 2-year study fared 5 years after starting in the BEVORDEX trial using retrospective data. Of the 88 eyes enrolled in the prior trial, 82% and 59% had three- and five-year data available, respectively. The authors found similar visual outcomes at the 5-year endpoint in both treatment paradigms (visual gains by the end of the trial were generally lost 5 years later). Eyes that were treated with intravitreal DEX-implant received fewer intravitreal injections, but had a higher rate of progression to proliferative diabetic retinopathy compared to those that had bevacizumab injections. These findings provide evidence that more aggressive intervention with intravitreal anti-VEGF injections in routine clinical care may improve long-term patient outcomes.

Controlling the Myopia Pandemic in Young Children


There’s another pandemic in town, and its name is myopia. Global health experts predict that about half of the world’s population will be myopic by 2025, a magnitude that will increase public health and economic burdens on our society. Notably, low concentration atropine has been shown to slow myopia progression. Utilizing 2-year outcome data from the Low-Concentration Atropine for Myopia Progression (LAMP) Randomized Control Trial, investigators analyzed 350 children between the ages of 4-12 years to determine the predictive factors of treatment response to 0.05%, 0.025%, and 0.01% atropine drops once nightly. Younger age of treatment was the only predictive factor associated with faster spherical equivalent progression and axial length elongation for all three treatment groups at 1 and 2 year follow-up (the younger the age, the poorer the response). In each age group, treatment response was found to be concentration-dependent; higher concentration (0.05%) resulted in better myopia control. The investigators suggest that because younger children have greater potential for myopia progression and decreased treatment response, they require a more aggressive starting dose of 0.05% atropine to reduce their potential of high myopia at older age. 

Ocular Involvement of Sjogren’s Syndrome

American Journal of Ophthalmology

Sjogren’s syndrome (SS) is a long-term autoimmune disease affecting the moisture producing glands of the body, most notably in the eyes and mouth. It has the potential to significantly impair visual acuity and lead to corneal damage, such as ulceration. In this retrospective case series, Singh et al. assess the risk factors for severe visual impairment (SVI) and resulting vision threatening corneal complications (ulceration or perforation) in SS patients. This study included 919 patients, 31% with primary and 64% with secondary SS (such as in Rheumatoid Arthritis). Among 1,838 eyes, 10% developed SVI, while only 2.5% had corneal complications. Risk factors for developing SVI were corneal scarring, corneal ulceration, low Schirmer values, cataract, glaucoma, and older age at diagnosis. Risk factors for corneal complications were the presence of scleritis and having secondary SS vs primary SS. The findings of this study reveal specific risk factors that clinicians should take note of when monitoring ocular symptoms of scleritis patients.

When is the right time to get my Disability Insurance?

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Quick Answer: The day before you became disabled (good luck with that). While the answer varies by situation, a good rule of thumb is purchase coverage as soon as you can afford it. Protecting your most valuable asset should not be swept under the rug for later. As physicians know best, in the most unexpecting times, life happens. Once your health is locked by purchasing a policy, your rate can never be change. Carriers also offer discounts on insurance to residents and fellows that disappear once you graduate so securing coverage during these few years will save thousands in the long run. Twin Oak was created to provide education, expert advice, and a streamlined experience. Twin Oak’s goal is to provide physicians a headache free option to protect their incomes. Check out Twin Oak’s blogs if you want to learn more about all things related to disability insurance or to request a complimentary comparison summary of all your top companies.


Severe bleeding in vitreoretinal surgery

Ophthalmology Retina

Estimated blood loss is not usually something we hear about in ophthalmology; this isn’t general surgery. In a prospective trial published in Ophthalmology Retina, researchers sought to determine the incidence of and risk factors for intraoperative bleeding events during pars plana vitrectomy and scleral buckling procedures. Post-operatively, 374 eyes were graded based on bleeding severity on a scale from 0 to 5, with 3 or greater indicating severe bleeding (​​endodiathermy or pressure needed to stop bleeding in vitrectomy; or extensive sub-retinal bleeding not limited to the periphery in scleral buckle). A severe intraoperative bleeding event was observed in only 4% of eyes. Risk factors that were significantly associated with severe bleeding included concomitant diseases such as diabetes mellitus and carotid artery stenosis, diabetic retinopathy, younger age, and external manipulation during scleral buckling. Interestingly, use of antiplatelet or anticoagulant agents, or both, had no significant influence on severe intraoperative bleeding events. This study had a representative sample of patients typically undergoing vitreoretinal procedures based on age and comorbidities and found a similar bleeding frequency to one previously reported in the literature (6.6%). With continued investigation, a standardized guideline for surgeons to follow will hopefully be on the horizon.  


The Association Between Vitamin D and Uveitis: A Comprehensive Review

Survey of Ophthalmology

You know what they say, “A glass of milk a day keeps the uveitis specialist away.” In addition to calcium homeostasis, vitamin D has many physiologic roles, including immunomodulatory, anti-inflammatory, and antioxidant functions. Consequently, hypovitaminosis D may promote a pro-inflammatory environment and possibly play a role in autoimmune disorders, particularly uveitis-associated diseases. This comprehensive review examines the relationship between uveitis and vitamin D, including vitamin D-associated genetic polymorphisms. Pillar & Amer conducted a search of PubMed and Medline databases using a set of key words to identify articles relating vitamin D and uveitis-associated diseases. Of the 186 studies identified by this method, 16 met inclusion criteria. The review found that uveitis-associated diseases, including HLA-B27-associated acute anterior uveitis, Vogt-Koyanagi-Harada (VKH) disease, sarcoidosis associated uveitis, and juvenile idiopathic arthritis-associated uveitis, were associated with hypovitaminosis D. Additionally, genetic polymorphisms in vitamin D binding protein and vitamin D metabolism genes correlated to uveitis development in patients with ankylosing spondylitis, Behçet's disease, VKH, and HLA B27-positive patients. Although a link between vitamin D and uveitis has been established, it does not yet indicate causality, further randomized control trials must be conducted. Additional research on genetic polymorphisms related to uveitis may expand our understanding and lead to improved diagnostics and treatments of uveitis-associated diseases.

Clinical Pearls

  • Anti-VEGF injections may also be useful in non-proliferative DR, not just proliferative DR
  • For pediatric myopia progression, younger age is associated with quicker progression, and a higher required atropine dose
  • Significant bleeding is rare in vitreoretinal surgery (~4%) and antiplatelet/anticoagulant medications do not appear to be associated with increased risk
  • Low levels of vitamin D are associated with increased risk of autoimmune-related uveitis
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Question of the Week

A 54-year-old male is referred to the ophthalmologist after visiting his primary care doctor for itchy eyes. He says that his eyes constantly feel dry and it often feels like there are particles of sand under his lids. He was recommended to use artificial tears, which he says have not provided full relief. Upon examination, visual acuity is 20/20. There is decreased tear film on the cornea. Below is a picture of the patient’s eyelids under magnification on the slit lamp.
Which is the best next step in management? 
A.    Doxycycline Ointment
B.    Lid scrubs with tea-tree oil
C.    Olapatadine hydrochloride drops
D.    Eye lash removal

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Quiz Answer: B
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