Current Issue

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In this week’s issue:

• Clinical features of retinoblastoma including neovascular glaucoma, intraocular hemorrhage, orbital cellulitis, and large tumor size predict high-risk pathologyl.
• Clinicians who receive gifts from pharmaceutical companies that make branded prostaglandin analogues are 50% more likely to prescribe them over generic. 
• Factors that predicted tube shunt failure included IOP <21 and neovascular glaucoma with a rate of tube failure of 38.8% after 5 years.
• Crystallin proteins are decreased in an animal model of glaucoma while adding back the proteins to retinal explants had neuroprotective effects.
• Sensitivity for detecting progression of glaucoma using yearly OCT measurements was <50%.

Ophthalmology

Retinoblastoma clinical presentation predicts development of high-risk pathologic features

New tools in the ocular oncologist’s toolbox. Standard treatment for retinoblastoma is primary enucleation, although chemotherapy is a newer alternative for globe salvage. To improve disease management, researchers examined the relationship between high-risk clinical features and high-risk pathologic features after removal. This study examined 942 eyes from 18 oncology centers. 282 (30%) of eyes showed high-risk pathologic features. Clinical features associated with these high-risk pathologic features included neovascular glaucoma, intraocular hemorrhage, aseptic orbital cellulitis, and tumor size greater than two-thirds globe volume. This study identified features that may help estimate prognosis at presentation and therefore better guide treatment plans to improve outcomes for children with high-risk retinoblastoma.  

JAMA Ophthalmology

Pharmaceutical company “gifts” affect prostaglandin analog prescribing patterns

You may want to reconsider your next dinner with a drug rep! Pharmaceutical companies have been mandated since the 2010 Affordable Care Act to report payments or transfers of value (TOV), such as meals, travel fees, and speaking gifts. Prostaglandin analogs come in either high-cost branded formulations (ie. Lumigan, Travatan, Zioptan) or as cheaper generics (Latanoprost). This retrospective analysis of 20,612 ophthalmologists and 5,426 optometrists assessed whether there was an association between TOV’s from companies that made prostaglandin drugs and branded prostaglandin prescription. In total, 9,685 clinicians received a TOV with a median value of $65 (range: $24-147). Overall, clinicians reporting a TOV were 50% more likely to prescribe branded prostaglandin than those that did not report a TOV (19.6% vs 12.9%, respectively). The top 10% of TOV recipients prescribed branded prostaglandins 29.2% of the time. The authors conclude that even relatively small TOV’s were associated with changes in prescribing patterns. This may increase medication costs for patients and may contribute to a lack of medication adherence due to these costs. Clinicians should be aware of these biases and try to take active steps to mitigate them. 

American Journal of Ophthalmology

When tube shunts fail, what is to blame?

Houston, we have a (tube shunt) problem! Tube shunts are devices implanted into a glaucomatous eye in order to drain excess aqueous fluid. In turn, the device mitigates glaucoma’s sequelae of high eye pressure and visual loss. This intervention may be needed when medications, laser, or other surgery has not worked. This study pooled data from 3 randomized clinical trials to determine what factors best predicted tube shunt failure. A total of 621 patents with medically uncontrolled glaucoma were included in this analysis. Factors associated with tube shunt failure included preoperative IOP <21, neovascular glaucoma, and placement with Ahmed valve. After 5 years, 38.8% of tube shunt surgeries had failed. Understanding what risk factors increase the probability of tube shunt failure can better guide when to use such an intervention and informs the general management of patients suffering from glaucoma 

IOVS

Crystallin proteins and neuroprotection in models of glaucoma

Crystallins: sending healing vibrations to the glaucomatous retina. Glaucoma is characterized by retinal ganglion cell loss and optic nerve head damage. In this study, Liu et al. explored the role of crystallin proteins in the development of and protection against glaucoma. Episcleral veins were occluded in a group of rats in order to raise IOP and simulate a model for glaucoma. Retinal explants were collected from rats, pigs, and a human donor for proteomics and cell-based studies. Several crystallin proteins (CRYAB, CRYBB2, and CRYGB) were found to have decreased abundance in rat glaucoma eyes. In vitro addition of these crystallin proteins to retinal explants was shown to be neuroprotective: Müller glial cells took up these crystallins and subsequently secreted several key neuron growth factors (CLU, VEGFA, and TGFb2). The findings of this study support the role of crystallin proteins as protective and suggest a mechanism of age-related glaucoma via their interaction with Müller glial cells. 

Ophthalmology 

Come back for another OCT scan in…. 3 months?

Do we know whether yearly OCT can accurately detect glaucoma progression? Evidence has been used to determine the reliability of OCT and errors in measurement, but there is no information on how many scans are needed to determine rate of peripapillary retinal nerve fiber layer (RNFL) thickness loss. Bradley et. al estimated the accuracy of diagnosing moderate (75th percentile) and rapid (90th percentile) progression at these criterion rates using simulations with data from 12,000 glaucoma and glaucoma suspect eyes. This study showed that an OCT RNFL once per year corresponds to a sensitivity of 47% for moderate progression and 40% for rapid progression. In order to obtain an accuracy of 60%, 7 scans would be needed over a 2-year period. It was also determined that clustered sampling (taking multiple scans at each visit) increased accuracy. Although implementation of increased OCT surveillance may be tedious, the authors recommended using more frequent scans and a clustered measurement strategy when practical.

 The Multicenter Uveitis Steroid Treatment Trial (MUST)

What must you do to effectively treat noninfectious uveitis? In the 2011 MUST trial, patients with noninfectious intermediate, posterior, or panuveitis from 23 centers were randomized to fluocinolone acetonide implant therapy (n = 129) or systemic therapy (n = 126) with two-year follow-up.

Key Points

• Both implant (+6.0 letters) and systemic therapy (+3.2 letters) improved mean visual acuity over 24 months, though the difference was not found to be statistically significant (P = 0.16)
• Residual active uveitis decreased to 12% for implant therapy and 29% for systemic therapy (P = 0.001) at 24 months follow-up
• Vision-related quality of life improved for both treatment groups

The MUST trial highlights the effectiveness of both forms of anti-inflammatory corticosteroid-based therapies for noninfectious uveitis. This is a landmark study as neither approach was determined to be superior to the other, allowing for choice of treatment to be based on pros and cons specific to a patient’s individual clinical circumstances.

 A 3-month-old boy presented to a pediatric ophthalmology clinic for concern of eye watering and mattering. His parents report that these symptoms have been ongoing since his first month of life and have not improved. His parents deny attempting any maneuvers for his tearing. He was born at full term and reached all developmental milestones.  His parents deny any illness or sick contacts. Physical examination is notable for increased tear lake and mucoid discharge in the right eye, which was exacerbated when the patient cried. 

What is the most likely management at this time for this patient’s condition? 

A. Nasolacrimal stents

B. Crigler massage

C. Dacryocystorhinostomy

D. Nasolacrimal duct probing and irrigation under general anesthesia

Click Here For Answers!