June 15, 2022

The most important ophthalmology research updates, delivered directly to you.

In this week's issue

  • Methotrexate and mycophenolate can be used as steroid-sparing treatment options in uveitic macular edema.
  • In retinopathy of prematurity, patients treated with primary anti-VEGF therapy compared with primary laser treatment had decreased incidence of amblyopia.
  • RNFL thinning of the papillomacular bundle seen on OCT imaging in premature infants can predict reduced visual acuity at nine months.
  • NTN-1, an anti-inflammatory factor, has reduced expression in a dry eye disease mouse model.

Spare the steroids: antimetabolites to treat uveitic macular edema


Can we cut the steroids in uveitic macular edema treatment? Noninfectious uveitic macular edema is a major cause of acute and chronic vision loss in patients with uveitis. Although corticosteroids are the mainstay of treatment, antimetabolite drugs can be used in conjunction to minimize the long-term adverse effects of steroid use. This study, part of the First-line Antimetabolites Steroid-sparing Treatment (FAST) trial, randomly assigned 55 eyes (41 patients) to mycophenolate and 42 eyes (30 patients) to methotrexate 12 months. These patients were initially treated with high-dose steroids, but were tapered down during this study. After 6 months, patients who failed to meet pre-specified success outcomes for central subfield thickness and visual acuity were switched to the other treatment group. At 12 months, macular thickness decreased by 30.5 mm in patients taking methotrexate and 54 mm in patients taking mycophenolate (p=0.73). Resolution of macular edema occurred in 37% of methotrexate treated eyes and 60% of mycophenolate treated eyes (p=0.10). These findings highlight the role of methotrexate or mycophenolate as non-steroidal alternatives for uveitic macular edema. However, in approximately 50% of patients, macular edema remained persistent after 12 months, suggesting the need for further research on other biologic therapies and likely continued use of steroids in some cases. 

The case for anti-VEGF therapy in retinopathy of prematurity

American Journal of Ophthalmology

A laser loss and anti-VEGF victory in the battle for treating retinopathy of prematurity. Retinopathy of prematurity (ROP) is a potentially blinding disorder of preterm infants that is characterized by disorganized retinal vasculature. The nature of ROP treatment has shifted from laser photocoagulation to anti-vascular endothelial growth factor (anti-VEGF) agents, with generally better outcomes. However, real-world visual outcome data in ROP are typically limited by short follow-up time, small datasets, and confounding variables. This retrospective, interventional case series was performed at 2 level IV neonatal intensive care units (NICUs). A total of 175 infants (350 eyes) hospitalized in the NICU who required ROP screening examinations were included for analysis between 2011 and 2019. Fifteen eyes received anti-VEGF therapy whereas 59 eyes received primary laser therapy. Primary anti-VEGF therapy, as compared with primary laser treatment, yielded a decreased incidence of amblyopia (adjusted odds ratio [aOR]=0.6-0.86) after controlling for gestational age and birth weight. Furthermore, there was an association between laser therapy and optic atrophy (OR=1.01-1.32). The link between preterm infants with ROP and adverse outcomes is well known. Anti-VEGF treatment is proving to be a more favorable treatment option over laser photocoagulation to prevent the serious consequences of this disease. 

Retinal microanatomical OCT changes to predict VA in preterm infants

JAMA Ophthalmology

Could OCT predict decreased vision in preterm infants with benign eye exams? Premature infants with an absence of retinal findings on ophthalmic examination have been shown to often have worse visual acuity (VA) at 6-year follow-up. Visualizing retinal microanatomy with optic coherence tomography (OCT) could identify subclinical changes and aid in recognizing infants who would benefit from early intervention. A prospective observational study was performed using data from 61 preterm infants from 2016-2019 to analyze the association between retinal microanatomical changes and VA at 9 months of age. Multivariate analysis showed a thinner retinal nerve fiber layer (RNFL) across the papillomacular bundle (PMB) (regression coefficient, −0.05 per 10-μm increase in RNFL thickness) was associated with worse VA at 9 months independent of gestational age, birth weight, and need for ROP treatment. OCT to identify RNFL thinning across the PMB could be used as an early screening marker for detection of preterm infants at greater risk for decreased visual outcomes before gross retinal changes are detected on ophthalmological exam.

Investigating a safety Net(rin-1) for dry eye disease


Dry eye disease may sound like it’s driven by a simple process, but this study explores the inflammatory factors that play a driving role. Yu et al. explore the balance of pro-inflammatory and anti-inflammatory factors on the ocular surface in dry eye disease (DED). Netrin-1 (NTN-1) is a protein that has been shown to have an anti-inflammatory effect as a negative guiding signal of leukocyte migration. Inflammatory cell infiltration and interactions are a key component of DED, which clinically is a chronic, progressive condition leading to eye burning, pain, and photophobia. To study this process, DED was induced in mice by subcutaneous scopolamine injection and a desiccating environment. Characteristics of DED were measured via RNAseq, RT-PCR, an immunostaining for inflammatory markers and cells. DED mice demonstrated decreased NTN-1 expression in the corneal epithelium. Topical administration of recombinant NTN-1 alleviated clinical signs of DED by restoring tear secretion and goblet cell density, and reduced the presence of dendritic cells and inflammatory factors to the conjunctiva. The findings of this study support the role of NTN-1 in modulating inflammatory response in DED, and identify a potential avenue for treatment.

Global Health

Ophthalmic and psychosocial sequelae in pediatric Ebola survivors

eClinical Medicine

What ophthalmologic sequelae are seen in Ebola survivors? Between 2013 and 2020 West African countries and the Democratic Republic of Congo experienced outbreaks of Ebola virus disease (EVD). The study examined the prevalence of eye disease, health-related quality of life, vision-related quality of life, and the burden of mental illness in pediatric EVD survivors in Sierra Leone.The cross-sectional observational study enrolled 23 pediatric EVD survivors and 58 EVD close contacts. Study participants underwent a medical history, a complete ocular examination, and completion of multiple surveys including Pediatric Quality of Life Inventory Version 4.0, Effect of Youngsters Eyesight on Quality-of-Life, and the Revised Child Anxiety and Depression Scale. Overall, 47.8% of EVD survivors and 31.9% of close contacts presented with an eye disease at the time of the study. A higher prevalence of uveitis was observed in EVD survivor eyes (10.8%) compared to close contact eyes (1.7%, p=0.03). Individuals diagnosed with an ocular complication had poorer vision-related quality of life. EVD survivors and their close contacts reported poor health-related and vision-related quality of life. To address the unmet needs of EVD survivors, cross-disciplinary approaches are needed in order to address the high prevalence of eye diseases associated with reduced vision health. 

Lens Landmarks

A drop a day can keep the… glasses away? Myopia is the most common eye disorder in humans and is associated with multiple irreversible blinding conditions including retinal detachment. Prior to this study, atropine was described as an agent that could slow progression, but there had been no long-term, randomized control trials. ATOM 1 is a randomized control trial in which children aged 6-12 with refractive error between -1.00D and -6.00D were randomized to either 1% atropine sulfate or vehicle eye drops once nightly for two years. 

Key Points:
  • Once-nightly dose of 1% atropine eye drops achieved a 77% reduction in progression of myopia over two years.
  • Atropine administration significantly slowed axial elongation.
  • There were no serious adverse effects related to topical atropine use.
This study was the first randomized control study to show slowing of myopia progression in children with atropine use. This study has limited extrapolation due to its limited study population (exclusively Asian children) and time course (two years). Additionally, there have been questions as to whether the effect lasted after stopping atropine, something that was examined in the ATOM2 study.

Question of the Week

A 23 year old patient presents to the ED with a slowly progressive decrease in vision for the past few years. The patient mentions he frequently rubs his eye as well as forgets to remove his daily contacts some nights. Corneal tomography shows central and inferior steepening. Results of a slit lamp exam, Scheimpflug image, and corneal biopsy are shown below:
What is the most likely diagnosis?

A. Meesman epithelial dystrophy
B. Keratoconus
C. Keratomalacia
D. Fuch’s Corneal Dystrophy

Keep scrolling for answer or click here

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Quiz Answer: B
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