Current Issue

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In this week’s issue:

• Reticular pseudodrusen were shown to confer additional risk for progression to late AMD, especially for geographic atrophy
• Lower-body negative pressure may not prevent Spaceflight Associated Neuro-Ocular Syndrome  
• 52-week results are reported for KESTREL and KITE studies of brolucizumab for DME 
• Choriocapillaris flow deficit percentage measured by SS-OCTA may reliably predict risk of referable diabetic retinopathy 

Ophthalmology

A new risk factor for AMD emerges: reticular pseudodrusen  

In the words of DJ Khaled, “Another one!” - reticular pseudodrusen now joins soft drusen, pigmentary abnormalities, and neovascularization as the three major risk features for progression to late AMD. Risk factors for age-related macular degeneration are used to create tailored patient plans for interventions, follow-up, and counseling. Currently, there are two scales to predict late AMD progression: (1) AREDS Simplified Severity Scale which is applied to an individual person, and (2) AREDS 9-step severity scale which is applied to individual eyes. However, both scales rely on only two risk factors, soft drusen and pigmentary abnormalities. This study was designed as a post hoc analysis of two previously performed clinical trials, AREDS and AREDS2, to determine rates of AMD progression based on three risk factors; soft drusen, pigmentary abnormalities, and reticular pseudodrusen (RPD). Color fundus photographs obtained at annual visits were graded for the three risk factors and outcome measures were late AMD progression, geographic atrophy, and neovascular AMD. According to the modified simplified severity scale, RPD correlated with AMD progression (HR 2.15), however, this relationship varied based on severity scale level (level 0-1, HR 3.23; level 2, 3.81; level 3, HR 2.28; level 4 HR 1.64). The 9-step scale also showed RPD was associated with increased risk of AMD progression and risk varied based on severity level. At low to moderate AMD severity, RPD presence indicates a high risk of progression to late AMD, with no significant difference for severe levels of AMD. Overall, RPD was shown as an additional risk factor for progression to late AMD, especially in geographic atrophy AMD, though not completely independent from the two traditional risk factors, soft drusen and pigmentary abnormalities. 

American Journal of Ophthalmology

KESTREL and KITE: brolucizumab for diabetic macular edema 

Seriously Bro(-lucizumab)? Brolucizumab is a single-chain antibody fragment that has a high affinity for vascular endothelial growth factor (VEGF). It also has a lower molecular weight than other anti-VEGF agents, delivering more drug per injection and offering the potential for more effective tissue penetration and increased duration of action, allowing Brolucizumab to be dosed every 12 weeks as opposed to requiring more frequent intravitreal injections. This report highlights the 1-year results from the KESTREL and KITE Phase III trials of brolucizumab for diabetic macular edema (DME). At week 52, brolucizumab 6 mg was noninferior to aflibercept in mean change of best corrected visual acuity from baseline, and more subjects achieved a central subfield thickness <280 µm with fewer having persisting subretinal/intraretinal fluid vs. aflibercept. Notably, incidence of ocular serious adverse events was 3.7% (brolucizumab 3 mg), 1.1% (brolucizumab 6 mg), and 2.1% (aflibercept) in KESTREL; and 2.2% (brolucizumab 6 mg) and 1.7% (aflibercept) in KITE. Authors concluded that these studies demonstrate clinically meaningful visual acuity gains and excellent anatomic improvements with an overall favorable benefit/risk profile; however, post-market surveillance will be critical to establish the true incidence of adverse events. This is important as brolucizumab use has been limited in the real world after numerous events of intraocular inflammation were reported.

JAMA Ophthalmology

Can we prevent spaceflight associated neuro-ocular syndrome? 

How do you conduct an ocular experiment in space? First, you planet. Prolonged space-flight time in astronauts can cause an increased cranial fluid shift, potentially leading to Spaceflight Associated Neuro-Ocular Syndrome (SANS). SANS can present with a constellation of symptoms, including hyperopia, disc edema, nerve fiber thickening, and cotton wool spots. This cohort study of 14 astronauts aimed to see if the application of lower-body negative pressure (LBNP) could serve as a countermeasure to SANS. LBNP is a technique in which the lower extremities are placed in a chamber where air is slowly removed, serving to redistribute fluids towards them. Compared with their pre-flight testing, on day 150 of spaceflight, the astronauts had a minimum rim width increase of 33.8 μm, a cup volume decrease of 0.038 mm3, a posterior displacement of Bruch’s membrane opening (neural canal opening) of 9.0 μm, and a macular thickness decrease of 5.1 μm (fovea to 500 μm diameter). After a 10 to 20 minute application of 25 mmHg LBNP, re-measurements of ocular parameters resulted in no changes. This study suggests that there are several ocular changes that occur due to long-duration spaceflight, but short-term LBNP may not be enough to mitigate them.. 

British Journal of Ophthalmology

Can swept-source OCTA be used to screen for diabetic retinopathy? 

Sometimes, it’s best to just go with the flow. Early detection of diabetic retinopathy (DR) is essential to preserve visual function. One proposed method is through visualization of choriocapillaris flow deficits (CC FD) using swept-source OCTA (SS-OCTA). In this prospective cohort study, patients with type 2 diabetes without history of ocular disease were enrolled from 2018 – 2020 and followed for one year (n = 1222) for incidence of referable DR (RDR) according to standardized DR severity grading score and compared with SS-OCTA measured CC FD in the macular region. A greater baseline CC FD% was associated with increased RDR incidence at 1-year in the entire macular area (10.59% vs 9.55%) or outer circle (10.44% vs 9.46%). Risk of RDR increased by 1.69 for each 1% increase in CC FD% of the entire area. Whereas CC FD% did not change significantly from baseline in individuals without incident RDR, CC FD% increased by 0.484% after one year in those who eventually developed RDR. As one of the first large, longitudinal studies that examines macular CC FD% and incident RDR using SS-OCTA, this study demonstrates the feasibility of CC FD% as a non-invasive biomarker to identify patients with T2D at greater risk for progression to  RDR.

Ophthalmology  

Is there a link between blurred vision and leukemia? 

If a patient presents with blurry vision, there might be more than meets the eye! Acute promyelocytic leukemia (APML) can be fatal if undiagnosed due to rapid progression of hemorrhage from disseminated intravascular coagulation. As such, it is crucial that early diagnoses be made, which can be challenging if patients with APML only present with optic neuropathy, cranial nerve palsies, papilledema, or hemianopia. Researchers presented a case series of patients who presented to a tertiary neuro-ophthalmology center with a neuro ophthalmology syndrome that later led to a diagnosis of APML. Three patients ranging ages 24 to 33 years presented with visual complaints of unilateral blurred vision or bilateral blurred vision. Physical exam revealed severe hemorrhagic papilledema with a venous sinus thrombosis, severe optic disc edema, and left homonymous hemianopia. CBC panels at the time of diagnosis revealed significant anemia and thrombocytopenia. Although future studies with a larger number of participants are warranted, recommendations in obtaining a complete blood count in patients presenting with optic disc edema are important. 

Amblyopia Treatment Study (ATS) - Atropine vs. Patching (2002)

Kids often dress up as pirates, but do they really want to keep their eye patches on after Halloween? Prior to this landmark study in 2002, the corrective treatment for amblyopia correction was almost exclusively patching. Still, concerns around compliance raised the question of whether medical penalization therapy (atropine) could be similarly effective. In this trial, children aged 3-7 with moderate amblyopia were randomized to be treated with either patching or 1% atropine in their non-amblyopic eye.

Key Points:

• Both patching and atropine led to significant visual improvement, with similar success rates (amblyopic eye VA 20/30 or better: 79% in atropine, 74% in patching) 
• Patching offered a more rapid recovery of vision at 5 weeks, and slightly greater visual improvement at 6 months (3.16 lines vs. 2.84 lines), but this difference was thought to be clinically insignificant 
• Patching compliance was slightly higher in the atropine group (95% in atropine, 83% in patching)      

The importance of this study was showing that both patching and atropine are effective in treating moderate amblyopia in children ages 3-7, with patching improving VA more rapidly and atropine being easier to administer as well as cheaper. 

See the the Lens Landmarks section for summaries of other landmark trials in ophthalmology!

A healthy 9-year-old male with no family history of vision problems presents after failing a vision screening test at baseball practice. The patient could not identify letters on the eye chart using his left eye. One year prior, the child was referred to an ophthalmologist after a school nurse identified poor vision in the left eye but the patient did not follow up. Ocular exam revealed leukocoria, light bulb aneurysms temporally, subretinal fibrosis with areas of exudation, and dilated telangiectatic vessels. What is the most likely diagnosis?

A. Retinopathy of prematurity 

B. Retinoblastoma 

C. Vitreous hemorrhage 

D. Coats disease   

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