July 27, 2022

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

In this week's issue

  • At 2-year follow-up for a trial of treatment for diabetic macular edema, there was no difference in visual outcomes between aflibercept monotherapy vs. initial bevacizumab therapy followed by a switch to aflibercept as needed.
  • A retrospective study finds that metastasis-free survival in uveal melanoma may be underestimated using a current cytogenetic assay.
  • A randomized control trial finds that horizontal placement of monofocal IOLs are shown to have lower incidence of negative dysphotopsia symptoms.
  • A study using a mouse model investigates the role of IL-19 in retinal neovascularization, possibly providing a new therapeutic target for diseases like proliferative diabetic retinopathy.

Bevacizumab or aflibercept for diabetic macular edema (DME): Is the grass always greener?

New England Journal of Medicine

Stay the course or switch things up? For patients with 20/50 or worse vision with DME this prior study found aflibercept (Eylea) had better visual outcomes than bevacizumab (Avastin). Given the relatively high cost of traditional anti-VEGF agents like aflibercept, many insurers now require initial treatment with the cheaper, off-label option, bevacizumab. Investigators set out to see if vision at 2 years was better in those with 20/50 or worse vision and started on aflibercept from the start compared to those who were started on lower cost bevacizumab then switched as needed based on vision and anatomic criteria (retinal central subfield thickness). Over the course of the study, 70% of eyes in the bevacizumab-first group switched to aflibercept treatment, with 57% switching between weeks 12 and 24. After two years, both groups had similar mean improvement in VA (between-group difference: -1.8 letters; p=0.37) and in retinal central subfield thickness from baseline (between group difference: -16 μm). Of note, serious adverse events occurred among 52% of those receiving monotherapy and 36% of those receiving bevacizumab-first therapy and the incidence of hospitalization was 48% and 32%, respectively. The results of this study are significant as they emphasize the safety and similar outcomes seen after treatment with an alternative anti-VEGF agent, which could decrease costs greatly for patients and the healthcare system.

Cytogenetic estimates of metastasis-free survival in patients with uveal melanoma

JAMA Ophthalmology

A not-so-magic 8 ball for predicting metastasis? Cytogenetic assays have been used to predict metastatic risk for patients with uveal melanoma. In addition to prognostication, the clinical utility of these assays includes guiding systemic surveillance for metastasis and eligibility for enrollment in adjuvant therapy trials. One such assay, developed by Castle Biosciences, stratifies patients into 3 risk categories (class 1A, 1B, and 2) for metastasis-free survival (MFS) based on the genetic expression profile of a biopsy sample. Reported 5-year survival estimates are 98% for class 1A, 79% for class 1B, and 28% for class 2. Despite frequent clinical use of the assay, little is known about the accuracy of these survival estimates. A retrospective study of 347 patients with uveal melanoma from two tertiary eye care centers compared observed MFS to a meta-analysis of 7 studies reporting MFS data and the estimates of Castle Biosciences. For 121 patients with class 2 tumors, MFS for the observational cohort was 47% (95% CI 37%-61%) at 5 years, which was similar to the meta-analysis, which estimated MFS as 40% (95% CI, 34%-46%) at 5 years. Furthermore, the 3- and 5-year MFS estimates reported by Castle Biosciences were beneath the 95% confidence intervals for both the observational data and meta-analysis. The observational data also showed that, of the patients with class 2 tumors, those with metastatic disease had larger tumors at baseline than those without (mean largest basal diameter difference 1.7 mm). These findings suggest that predictions of the genetic expression profile underestimate MFS. The authors suggest that including tumor size alongside cytogenetic data may improve the predictive value of these models.

What’s the best intraocular lens (IOL) position to decrease post-op dysphotopsia?

American Journal of Ophthalmology

When perfection is expected, every detail matters! Dysphotopsias are central or mid-peripheral visual artifacts that patients can experience secondary to cataract surgery and a leading cause of patient dissatisfaction after surgery. Positive dysphotopsia are bright artifacts such as halos, arcs, or streaks while negative dysphotopsia are dark shadows due to light blockage. A prospective, randomized clinical trial investigated the effect of horizontal, vertical, superonasal, and inferonasal optic-haptic junction position of monofocal IOLs on the incidence and severity of post-op dysphotopsia in 326 eyes. While there was no statistically significant difference in positive dysphotopsia, the eyes with horizontally implanted IOLs had the lowest rates of positive dysphotopsia (12 eyes, 16.7%) at 4-6 weeks postoperatively. Negative dysphotopsia symptoms were found to be significantly higher in those with superonasally implanted IOLs at both 1 week and 4-6 weeks, with rates of 22.3% and 17% respectively, and lowest for horizontally implanted IOLs with only 2 eyes (2.8%) reporting symptoms at 4-6 weeks. These results support horizontal placement of monofocal IOLs to decrease dysphotopsia symptoms. Future studies can build upon these findings with longer follow-up, confirmation of IOL placement with imaging, and evaluation of monocular symptoms with a greater number of participants.

Could IL-19 inhibitors be the new anti-VEGF?


Could IL-19 inhibitors be the new anti-VEGF to counteract neovascularization? Hypoxia is the leading cause of pathological retinal neovascularization found in ischemic retinopathies such as proliferative diabetic retinopathy (PDR) and retinopathy of prematurity (ROP). Pathological neovascularization is detrimental to vision as it can lead to hemorrhage, fibrosis, and retinal damage. This study investigated the role of IL-19, a cytokine secreted mainly by monocytes, in promoting neovascularization directly and indirectly via stimulation of proangiogenic M2 macrophages. Using a mouse model of oxygen-induced retinopathy (OIR), retinas from these experimental mice showed significantly elevated levels of IL-19 mRNA and protein. Intravitreal injections of high dose recombinant IL-19 (rIL-19) or macrophages previously stimulated with rIL-19 further increased pathological neovascularization and inhibited physiological vascularization. Knocking out IL-19 significantly decreased gene expression of ARG1 (an M2 macrophage marker) and VEGFA (vascular endothelial growth factor), as well as protein levels of VEGFA and STAT3 (a transcription factor promoting cell growth).These results suggest that IL-19 promotes pathological neovascularization directly and indirectly by stimulating M2 macrophages. The authors concluded that IL-19 may be a target for therapeutic agents for retinal neovascular diseases as inhibiting its action would decrease proangiogenic factors such as VEGFA and prevent activation of M2 macrophages.


Sensitivity and specificity of the ABCD classification for keratoconus progression


Learning the ABCD’s of keratoconus is so E-Z! Keratoconus (KC) is a progressive corneal disorder where the central or paracentral cornea undergoes progressive thinning and steepening causing irregular astigmatism and myopia. Collagen cross-linking (CXL) is an effective treatment to slow KC progression and is used early when there are signs of progression to avoid visual acuity loss. Several softwares have been developed to diagnose KC, but it is not always clear clinically whether progression has occurred. This study aimed to evaluate the sensitivity and specificity of the “ABCD” classification (A: anterior elevation, B: posterior elevation, C: corneal thickness, D: visual acuity) in detecting progression of KC. This was a retrospective study of 30 KC patients (21 with progression, 9 stable) that underwent CXL procedures between 2016 and 2018. Progression by criterion 1 (change in 2 parameters above 80% CI) resulted in sensitivity of 61.9% and specificity of 88.9%. Progression by criterion 2 (change in 1 parameter above 95% CI) resulted in higher sensitivity (80.9%) and specificity (100%). There was no significant difference in the proportion of subjects with change in the D parameter between the groups. The ABCD progression display could assess KC progression with high sensitivity and specificity, although this study is limited by small sample size, short follow-up time, significant progression in this group, and lack of patient input. Further studies evaluating against other progression criteria, with larger cohorts, or with more clinical data are warranted to improve generalizability and applicability.

Lens Landmarks

Time to eat your veggies to prevent cataracts! In the 1991 LOCS study, risk factors were determined for the development of nuclear, cortical, posterior subcapsular, and mixed cataracts using 1380 patients with known cataracts. There were 435 controls alongside 72 posterior subcapsular, 137 nuclear, 290 cortical, and 446 mixed cataracts.

Key Points:
  • Cataracts are related to low socioeconomic and nutritional status.
  • Diabetes is a risk factor for all types of cataracts except for nuclear.
  • Oral steroid use increased risk for posterior subcapsular cataracts.
  • Risk factors for cortical cataracts: nonwhite race and female sex.
  • Risk factors for mixed cataracts: gout medications, family history, and myopia.
Overall, the LOCS study is a landmark study because it determined the various personal, nutritional, medical, and other exposures that lead to cataract formation, which are now part of numerous clinical discussions around the development of cataracts.

Question of the Week

A 6 month-old boy with no known medical problems is forwarded to your clinic by his pediatrician for evaluation of tearing, shying away from light, and rubbing of both his eyes. His parents report no history of eye diseases in their families. 

Initial exam demonstrates IOP > 30mmHg in both eyes, with an enlarged corneal diameter of 12 mm, as well as the corneal findings in the image below. Cycloplegic retinoscopy demonstrates high myopia in both eyes. Gonioscopy reveals deep angles without angles recesses in both eyes. No other ocular or systemic anomalies are appreciated. Under anesthesia, fundus exam demonstrates an increased cup-to-disc ratio in both eyes.
What is the most likely etiology of this patient’s symptoms? 

A. Primary congenital glaucoma
B. Juvenile open-angle glaucoma
C. Axenfeld-Rieger Syndrome
D. Peters Anomaly

Keep scrolling for answer or click here

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