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Emerging trends and hot topics in glaucoma from the 2015 ARVO annual meeting
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Anthony P. Khawaja
Attending the Association for Research in Vision and Ophthalmology annual meeting can be daunting for the young ophthalmologist, and identifying the most important research among the hundreds of presentations is a huge task. Fortunately, the Allergan European Glaucoma Panel of young budding glaucoma specialists has debated and collated a list of the best research in the field from ARVO this year.
Anthony P. Khawaja, PhD, FRCOphth
Chair of the SOE Young Ophthalmologists committee
Once again, the ARVO annual meeting gave participants the opportunity to discover the latest and most innovative research being conducted in ophthalmology. Below are the highlights of the most relevant and promising research topics in glaucoma that we identified at this year’s meeting held in Denver, USA, to share with our colleagues throughout Europe.
Automated OCT -based 24-2 visual threshold estimation
Abramoff and colleagues in Iowa, USA, demonstrated that an automated OCT-based 24-2 visual threshold estimation based upon structural information derived from both retinal nerve fiber layer and ganglion cell layer-inner plexiform layer thicknesses had an incomplete but good correlation with SAP SITA Humphrey 24-2 in patients with all stages of open-angle glaucoma, with better intraindividual repeatability (0.98 vs. 0.88). This promising approach may complement visual field testing for patients who struggle or cannot perform those tests and may be adapted to future OCT technology to increase its correlation with subjective visual field data.
Muriel Poli
Marcos Muñoz
Imaging improves accuracy of visual field progression analysis
Garway-Heath and colleagues in London demonstrated that imaging could be used to improve the accuracy of visual field progression analysis in glaucoma. A new, more accurate method for visual field progression analysis, called ANSWERS (analysis with non-stationary Weibull error regression and spatial enhancement), which takes into account increasing measurement variability as glaucoma progresses, produces significantly more accurate predictions than ordinary linear regression in predicting future visual fields over a short period of time and with lower prediction errors. Incorporating the rate of structure progression with visual field measurements further improves both prediction accuracy and predictive error. More accurate prediction of visual fields will help clinicians to better define individual target pressure.
Mitochondrial flavoprotein fluorescence assessment for early diagnosis of glaucoma
The crucial role of mitochondrial dysfunction in the pathogenesis of glaucoma and many other degenerative diseases has been clearly established. Pinhas and colleagues in New York studied macular mitochondrial flavoprotein fluorescence in eyes with primary open-angle glaucoma. They aimed to quantitatively compare mitochondrial dysfunction in the maculae and optic nerve of patients and healthy controls, and observed that macular mitochondrial flavoprotein fluorescence, IOP and cup-to-disc ratio were weakly correlated. By detecting an increased mitochondrial dysfunction in primary open-angle glaucoma, this novel approach may detect functional changes earlier than structural changes. Nevertheless, our panel members questioned the possible detection of mitochondrial activity in photoreceptors, which could interfere with that in the retinal ganglion cells.
Novel in vitro model of tissue contraction and inflammation
Modulation of wound healing is challenging because both inflammation and fibroblast-mediated tissue contraction underlie scarring and treatment failure after glaucoma filtration surgery. Sharma and colleagues in London presented a novel in vitro model of tissue contraction and inflammation in fibrosis after glaucoma filtration surgery. This new device could shed light into the role of fibroblasts and macrophages in scarring, and provide the possibility to assess the effect of anti-scarring agents on this process.
MicroRNAs in glaucoma pathogenesis
MicroRNAs are small, endogenous non-coding RNAs that modulate post-transcriptional gene expression. The work of Jayaram and colleagues in Portland, USA, showed evidence that changes in retinal microRNA expression are observed in glaucomatous rat models, demonstrating similarities to comparable mechanisms observed in central nervous system injury. Gaasterland and colleagues in San Diego, USA, also presented preliminary data of in vitro microRNA expression in a glaucomatous human optic nerve. This cutting-edge approach in understanding the pathophysiology of glaucomatous optic neuropathy may ultimately lead to novel therapeutic interventions to attenuate the mechanisms that lead to glaucomatous damage.
Scleral and trabecular meshwork stiffness, MGP gene and glaucoma
Recent studies indicate that age-associated increased stiffness of the trabecular meshwork and sclera could play a crucial role in the pathogenesis of glaucoma. Matrix Gla protein (MGP), an inhibitor of calcification with anti-stiffness properties, has been identified in the trabecular meshwork and sclera. Borras and colleagues in North Carolina, USA, investigated the expression and distribution of MGP in MGP knock-in mice and found high levels of MGP in the peripapillary sclera as well as in the trabecular meshwork. This study contributes to stiffness theory in glaucoma pathogenesis and may identify a potential therapeutic candidate through which stiffness may be regulated in glaucoma models using a gene therapy approach.
Influence of VEGF on conventional outflow facility
Overby and colleagues in London assessed the influence of VEGF, which regulates the permeability of vascular endothelium, on the conventional outflow facility and thus on IOP. Because VEGF is present in aqueous humor and VEGF receptors are expressed by Schlemm’s canal endothelium, they measured the effects of VEGF and anti-VEGF on outflow facility in mice and humans. Inhibition of VEGF signaling was observed to lead to a reduction in outflow facility. Therefore, anti-VEGF therapy may contribute to the sustained IOP elevation reported in a subset of patients treated for retinal disease.
We would like to thank Tuan Ho, PhD, of Moorfields Eye Hospital, facilitator to the program, for his helpful comments.
- For more information:
- Muriel Poli, MD, PhD, can be reached at the Centre Hospitalier Universitaire de Lyon, Lyon, France; email: murielpoli@hotmail.com.
- Marcos Muñoz, MD, can be reached at the Institut Català de Retina, Barcelona, Spain; email: marcosmunioz@gmail.com.
- Co-authors of this work are Sabina Anderson (Sweden), Laura Beltran-Agullo (Spain), Mehmet Cem Mocan (Turkey), Maurizio Digiuni (Italy), Cornelia Hirn (Switzerland/Austria), Hari Jayaram (UK), Themis Karmiris (Greece), Sergio Mahave (Spain), Juliane Matlach (Germany), Karl Mercieca (UK), Manuele Michelessi (Italy), Eduardo Normando (UK), Luis Abegão Pinto (Portugal/Belgium), Verena Prokosch-Willing (Germany), Gokulan Ratnarajan (UK), Andrew Scott (UK) and Katarzyna Skonieczna (Poland). With Poli and Muñoz, they are members of the European Glaucoma Panel and Mentoring Program, a 3-year educational and personal development program for young glaucoma specialists from Europe with a keen interest in research under the mentorship of David Garway-Heath, MD, FRCOphth, of Moorfields Eye Hospital and UCL Institute of Ophthalmology, London..
Disclosure: Poli and Muñoz report no relevant financial disclosures.