November 2, 2022

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

In this week's issue

  • Retinoblastoma presenting with orbital cellulitis can be differentiated from tumor invasion by MRI.
  • Patients with higher IOP variations had greater RNFL structural changes.
  • Clarifying time to surgery for RRDs: within 24 hours is best for mac-on, within 3 days is best for mac-off.
  • 35.9% of glaucoma medications are not filled within 1 month of the date prescribed by clinicians.

Inflammation versus tumor infiltration: Can we trust the MRI?


Eye spy with my MRI… Retinoblastoma rarely can incite a sterile orbital cellulitis. It can present as soft tissue swelling, chemosis, uveitis, iritis, increased pressure or buphthalmos (eye enlargement). This sterile inflammatory reaction must be distinguished from tumor invasion. A retrospective review of 236 patients (311 eyes) with retinoblastoma was conducted to understand the prevalence of orbital cellulitis using magnetic resonance imaging (MRI). In a sub-analysis, they compared 30 retinoblastoma patients with orbital cellulitis to 30 controls (retinoblastoma without orbital cellulitis) to assess for phenotypic differences on MRI. The presentation of retinoblastoma-associated orbital cellulitis showed more necrosis, uveal inflammation, uveal hemorrhage, lens dislocation, and buphthalmos. On MRI, 67% of retinoblastoma-associated orbital cellulitis cases had post-laminar optic nerve enhancement (PLONE). Of those with inflammatory PLONE (as opposed to invasive PLONE), 0% had optic nerve tumor invasion on histopathology. In contrast, 50% of eyes with invasive PLONE had tumor invasion on histopathology. In conclusion, further subdividing PLONE into inflammatory and invasive patterns increased specificity for post-laminar tumor invasion in retinoblastoma-associated orbital cellulitis from 32% to 89%.

Associations between intraocular pressure and RNFL thinning

JAMA Ophthalmology

Intraocular pressure remains the most important metric in managing glaucoma. A characteristic change in glaucoma is the thinning and degeneration of the optic nerve. This presents with a decreased field of vision, loss of visual acuity, and a risk for potential blindness. Thus, it is important to measure and manage intraocular pressure (IOP) to mitigate glaucomatous changes in at-risk patients. This retrospective cohort study utilized intraocular pressure (IOP) measurements and optical coherence tomography (OCT) images from 815 eyes with glaucoma from 508 patients. Utilizing a linear mixed-effect model, the correlations between IOP measurements and changes noted on OCT were examined. In all glaucomatous patients, the mean rate of retinal nerve fiber layer (RNFL) change was -0.67 μm per year. When the analysis was remodeled for mean intraocular pressure, patients with a higher standard deviation of IOP had a greater degree of RNFL change of -.20 μm per 1-mm Hg increase in IOP standard deviation. Of those patients with a higher IOP range, there was an associated RNFL change of -0.05 μm per 1-mm Hg IOP increase. This study reiterates the importance of IOP measurements throughout the course of glaucoma treatment, and special care should be given to those who have a greater IOP measurement to prevent optic nerve changes.

Time to surgery in rhegmatogenous retinal detachment

American Journal of Ophthalmology

To preserve the sight, try not to wait one more night. Rhegmatogenous retinal detachment (RRD) is a very serious condition that involves the separation of the neurosensory retina from the underlying retinal pigment epithelium (RPE) by fluid from the vitreous cavity imposing on the subretinal space. Though postoperative visual outcomes can vary, immediate surgical repair is ideal. As these surgeries can experience delays (e.g. staffing availability, the “weekend” effect), it is crucial to understand how long both macula-on and macula-off RRD repair can be delayed without risking further visual perturbation. Researchers performed a meta-analysis for randomized controlled trials and observational studies comparing best-corrected visual acuity (BCVA) based on time to RRD repair (scleral buckling [SB], pars plana vitrectomy [PPV], combined SB and PPV, or pneumatic retinopexy). A total of 1929 eyes were included at baseline. Macula-off RRD repair within 0-3 days from symptom onset was superior to 4-7 days for final BCVA, by ~3 Snellen letters. BCVA in macula-on RRD proved superior when performed within 0-24 hours as opposed to >24 hours after presentation, by ~1 Snellen letter. For macula-on RRDs, more urgent surgical repair is warranted to spare vision. For macula-off RRDs, urgency can be tempered as there are less significant differences in visual prognosis with later repair.

Under pressure: Tissue remodeling in glaucoma optic nerve head


Can lamina cribrosa structural changes be quantified to correspond with disease severity? The lamina cribrosa (LC) is a mesh-like component of the optic nerve head (ONH) that supports retinal ganglion cells as they form the optic nerve, and is an important site of damage in glaucoma. This study quantitatively measured changes to the LC cell and connective tissue composition in human eyes, exploring potential biomarkers of glaucoma incidence and progression. 27 open-angle glaucoma and 19 age-matched postmortem eyes were included in the study, with LC cross-sections examined by serial confocal, light, and electron microscopy. Groups were based on disease status and degree of nerve damage. The degree of retinal damage in glaucoma eyes correlated with wider F-actin process width (P=0.042), thinner LC connective tissue beam width (P=0.042), and increased nuclear density (P=0.019) in LC pores. Increased nuclei were determined to be chiefly astrocytes via SOX9 staining, and occurred with increased deposition of collagen IV fibers. Taken together, results indicate that LC remodeling in human glaucoma includes intrusion of astrocytes into ONH axonal bundles, deposition of basement membrane material, and thinning of protective connective tissue beams.


Are we “eye-dropping” the ball on glaucoma meds?

Journal of Glaucoma

I’m not naming names…but someone’s got butterfingers! Glaucoma treatment and adherence involves a complex set of factors. With most prescriptions now electronic, additional barriers to physically obtaining the necessary treatment may be disproportionately affecting individuals with lower socioeconomic status. While previous studies have discussed systemic errors in prescription refills in primary care literature, this study aimed to broaden the impact in ophthalmic literature. In this retrospective, cross-sectional study, 198 glaucoma medications of 145 patients were evaluated over 6 weeks to identify medications that were not filled. Over one third of glaucoma medications were not obtained within 1 month (35.9%), with patients citing insurance coverage and pharmacy availability as their primary barriers. Particularly, medications requiring prior authorization were less likely to be obtained with no significance attributed to class of medication (all p<0.05). While this study does not fully elucidate the reasons for patients not filling medications, it highlights the urgency for addressing barriers to access or modification of care (increasing use of SLT, for example).

Lens Landmarks

Can you predict which patients with Thyroid Eye Disease will respond to immunosuppressive treatment? In this 1997 study, patients with Graves’ Ophthalmopathy were assessed using the Clinical Activity Score (CAS) and treated with oral prednisone (n = 22) or retrobulbar irradiation (n = 21) and graded on their response to treatment based on the CAS.

Key Points:
  • There was no statistical difference in outcomes between the treatment modalities.
  • The pretreatment CAS was significantly higher in responders than in non-responders. 12/22 responders and 3/21 non-responders had a CAS > 4 (55% vs 14%; P < 0.01).
  • Using CAS of 4 as cut-off point, the accuracy of CAS in predicting the therapeutic outcome was: specificity 86%, sensitivity 55%, positive predictive value 80%, negative predictive value 64%.
Overall, the CAS Graves’ Ophthalmopathy study is a landmark study because it offered an easy, inexpensive, and entirely clinical score that providers can use to predict which patients are more likely to respond to immunosuppressive therapy. These data can be used to assist clinical decision-making and patient satisfaction in the treatment of Thyroid Eye Disease.

Question of the Week

A 38 year old female presents to the ophthalmologist with progressive “bulging” above her left eye. She also reports pain and photophobia. External examination and fundus exam are shown below:
In working up this patient, all of the diagnostic tests below are appropriate for this case except:

A. Chest imaging
B. HLA-B27 testing
C. Imaging of the orbit/head
D. Biopsy

Keep scrolling for answer or click here

Helpful Links

Quiz Answer: B
Quiz Answer Explained
Twitter Twitter
Website Website
Share with a friend Share with a friend
Copyright © 2022 The Lens Newsletter LLC, All rights reserved.