September 28, 2016
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Emerging trends and hot topics in glaucoma from 2016 ARVO meeting

Members of the International Glaucoma Panel identified some of the most relevant and promising research topics.

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The Association for Research in Vision and Ophthalmology annual meeting can be overwhelming for a young ophthalmologist, with vast numbers of new studies presented in parallel sessions. On behalf of the International Glaucoma Panel, a young mentoring group, Marcos Muñoz, MD, and Karl Mercieca, MD, share with us their top glaucoma studies presented at ARVO 2016.

Anthony Khawaja, PhD, FRCOphth
Outgoing Chair of the SOE Young Ophthalmologists committee

The Association for Research in Vision and Ophthalmology annual meeting, which was held this year in Seattle, gave participants the opportunity to discover the latest and most innovative research in ophthalmology. We give here an overview of the most relevant and promising research topics in glaucoma presented at the meeting.

This selection has been identified by all of the members of the International Glaucoma Panel (IGP). The IGP and Mentoring Program is a 3-year educational and personal development program for young glaucoma specialists from all over the world with special interest in research. Under the mentorship of Prof. David Garway-Heath of Moorfields Eye Hospital and UCL Institute of Ophthalmology, London, and facilitated by Dr. Tuan Ho of Moorfields Eye Hospital this program, among other aspects, focuses on the selection and critical discussion of the most relevant findings from key scientific meetings. This exercise aims at providing the IGP members with in-depth insight into glaucoma. Below is the summary of our collaborative work, which we would like to share with our colleagues outside the IGP and mentoring program.

Marcos Muñoz

Restoration of trabecular meshwork cellularity and function following iPSC transplantation in vivo

The purpose of this study was to determine if restoration of trabecular meshwork cellularity using trabecular meshwork cells derived from induced pluripotent stem cells (iPSC) can lead to a lasting functional rescue of the trabecular meshwork in a genetic mouse model of the disease. The work of Kuehn and colleagues from Iowa, USA, included 22 MYOCY437H mice injected with iPSC in the anterior chamber and three control groups: 16 sham injections, eight fibroblast injections and 20 age-matched wild-type mice. When compared with the sham injection group, animals having received iPSC-TM displayed significant lower IOP, higher aqueous humor outflow facility, higher retinal ganglion cell density and higher trabecular meshwork cellularity. While interesting, the results from fibroblast injections were not presented for comparison. MYOCY437H mice may not accurately represent human glaucoma, and further evaluation is needed to determine if a long-term sustained effect on IOP and retinal ganglion cell survival is achievable.

Genome-wide pathway approach to dissect POAG

Cooke and colleagues from the USA conducted a collaborative work across the USA using genetic data from NEIGHBORHOOD, one of the largest collections of primary open-angle glaucoma (POAG) cases and controls. Using software that predicts the pathway according to the location of the single nucleotide polymorphism in the genome, five phenotypes were analyzed: POAG, NTG, HTG, POAG + female and POAG + male. Two hundred ninety-three pathways were identified, with 33 significant pathways involving 1,882 genes, and 42 genes were observed in more than two pathways. Seven genes were significant in all five phenotypes studied. We think this is a well-conducted study that tries to identify new pathways and driver genes in order to define future diagnostic markers or therapeutic targets in glaucoma.

Investigation of floor effect for OCT structural measurements in advanced glaucoma

Defining floor effect as tissue thickness after structural loss not detectable while functional changes continue, Bowd and colleagues from California, USA, described the relative floor effects for minimum rim width, peripapillary retinal nerve fiber layer (RNFL) thickness and retinal ganglion cell-inner plexiform layer thickness measured with spectral-domain OCT. The mean percentage of image area that did not reach the floor was 14% for circular RNFL thickness, 25% for volume RNFL thickness, 19% for the minimum rim width and 36 % for ganglion cell-inner plexiform layer. The authors concluded that different SD-OCT structural measurements display different floor effects in advanced glaucoma and areas that are less damaged may still be used to monitor glaucoma. Further studies are needed to determine if relative floor effects among the parameters investigated reflect the dynamic range of measurements useful for detecting change over time.

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Lamina cribrosa pore tortuosity in healthy and glaucomatous eyes

Wang and colleagues from Pennsylvania, USA, researched the hypothesis that axons take a more tortuous path through the lamina cribrosa in glaucoma patients compared with healthy eyes. An in vivo study using optic disc scans from a swept-source OCT system was done. Ten healthy subjects, 23 glaucoma suspects and 48 glaucomatous eyes were included. Lamina cribrosa pore segmentation was automatically performed using a validated custom-made algorithm. Lamina cribrosa pore path track and tortuosity were quantified using custom MATLAB and ImageJ software. A higher pore variability and tortuosity was found in glaucoma patients compared with healthy patients (P < .05). Further research is needed to determine the causality of the relationship between pore tortuosity and glaucoma damage, as assessed by visual fields.

Visual field analysis tools for real-world clinics

Brian and Crabb from London demonstrated a new approach for assessing visual field progression in clinics using two parameters: rate of progression and loss of sight years, which estimates the number of years that a patient will have bilateral visual field loss worse than a median deviation loss of –20 dB in their predicted remaining lifetime. Also, reliability of rate was determined for each patient based on the variability in the median deviation loss recorded in both eyes. They concluded that rate of progression and loss of sight years can be ranked for all patients in a clinic in order to help identify worse cases of visual field progression. Hedgehog plots provide a tool for clinicians to visualize all of their glaucoma patients simultaneously and could be helpful in prioritizing clinical care.

New image-based digital gonioscope device for iridocorneal angle imaging

Aquino and colleagues from Singapore assessed the Nidek NGS-I image-based digital gonioscope device to determine its utility in capturing reliable images of iridocorneal angle. Sixty-five eyes of 37 patients were included, and pictures were taken with a prototype optical gonioprism with built-in camera. Sixteen images per eye were taken covering 360° of the angle. Out of 16 images per eye, 13.6 ± 1.5 images were adequate to identify angle structures including iris processes, trabecular meshwork pigmentation and peripheral anterior synechiae. We consider that further work is needed to improve image quality. Also, because the device touches the eye during the examination, a safety evaluation should be performed.

Early glaucoma detection using chromatic pupillometry

Growing evidence indicates that measuring pupillary responses to different wavelengths and irradiances of light can be used to assess inner vs. outer retinal degeneration. Based on intrinsically photosensitive retinal ganglion cells and visual photoreceptor differences in their light response properties, Najjar and colleagues from Singapore demonstrated that light-induced percentage pupillary constriction from baseline was reduced in early-stage POAG, specifically at moderate to high irradiance levels for both blue light (P < .05) and red light (P < .001). The average maximum pupil constriction was significantly reduced by 14.2% to blue light and 9.3% to red light in POAG compared with controls. They concluded that early-stage POAG is associated with reduced pupillary response to monochromatic light. Although promising, further work is needed to determine how specific this is in glaucoma.

OCT angiography of macular ganglion cell complex circulation in glaucoma

Takusagawa and colleagues from Oregon, USA, studied macular circulation defects in glaucoma using OCT angiography imaging. The retina was segmented into ganglion cell complex (GCC) defined as the nerve fiber layer to inner plexiform layer, and inner nuclear layer plus outer plexiform layer (INL+OPL). The total retinal circulation was analyzed (GCC plus INL+OPL), and vessel density was evaluated in 30 glaucomatous subjects and 30 healthy controls. Data showed that GCC and total retinal vessel density were significantly lower in glaucoma but not INL+OPL vessel density with 90% of sensitivity at 95% of specificity. They concluded that glaucoma preferentially affects vessel density in the GCC. We consider this tool to have potential in differential diagnosis from non-glaucomatous optic neuropathies and possibly in normotensive glaucoma.

Disclosure: Muñoz reports no relevant financial disclosures.