New concepts in diagnosis and treatment

In the past decade, several significant advancements have been made in the arena of glaucoma diagnosis. Spectral domain optical coherence tomography (SD-OCT), newer algorithms in trend analysis of visual field studies, and combined visually evoked potential (VEP) and pattern electroretinography (ERG) studies have been the hallmarks of such recent advancements. 

I delivered two lectures recently at a conference in Halifax, Nova Scotia, which highlighted recent novel devices and concepts in glaucoma diagnosis and treatment.

Diagnosis advancements

The first course was on diagnostic advancements, and it included a review of where we are with SD-OCT studies, VEP/ERG analysis, and visual field analysis and progression algorithms. I also covered conceptual considerations, such as low cerebral spinal fluid pressure and its potential link to glaucoma.

Previously from Dr. Casella: Helping patients better understand glaucoma

The second course, which went through potentially promising therapeutic approaches on the horizon, left the audience with one cold hard fact: With all that we can do on the diagnostic side of glaucoma, there has yet to be a therapeutic approach to date which should come before lowering intraocular pressure (IOP). ODs need to look for signs earlier and treat glaucoma early on in an effort to preserve ganglion cell vitality and its corresponding visual function.

Someday, the future of glaucoma therapeutics will likely deliver a novel neuroprotective approach that will be proven effective in preserving ganglion cells. However, it is always important to treat glaucoma earlier in the hopes of preserving visual function.¹ ODs are left with the task of detecting glaucoma earlier or-perhaps more conceptually-determining which patients will get glaucoma.

Research findings

A small but potentially significant study was recently published. The authors purported to have accurately and safely identified apoptotic neurons in the retinas of glaucoma patients.² The investigators labelled a molecule known as annexin A5 with a fluorescent dye and injected it into patients intravenously in combination with detecting of apoptosing retinal cells (DARC)-an imaging technique.

Related: Standards of care in treating glaucoma

The DARC count is defined as the number of apoptosing retinal neurons.  This metric was found to be higher in patients with progressing glaucoma.²

Whether patients have sick or healthy neurons, apoptosis (programmed cell death) occurs in all people It is commonly accepted that apoptosis accelerates early on in glaucoma (and other neurodegenerative diseases, for that matter).³

This early sign of the disease has been elusive to in vivo assessment in humans. If this novel imaging technique proves to be effective (more and larger studies are needed), then it could become possible to identify and stage glaucoma in its earliest form.

A major implication with respect to this study is that it may be possible to identify the presence or progression of glaucoma much earlier than contemporary clinical application of science permits. The ability to intervene earlier on in patients who need intervention could lead to better patient outcomes.

Another major implication would be the possible application of a biomarker for progression in patients already being treated for glaucoma. It can be inferred that the rate of accelerated apoptosis in glaucoma patients could someday be directly measured as a means of determining the effectiveness of therapy.

Related: How alcohol consumption correlates with glaucoma

Applying treatment options

Target IOP is defined as the IOP at which glaucoma does not progress. We make use of major landmark studies such as the Ocular Hypertension Treatment Study⁴  and the Collaborative Normal-Tension Glaucoma Study⁵ to guide us as to how aggressive we should be in setting our initial target IOPs in glaucoma patients or glaucoma suspects.

If a patient’s glaucoma progresses, by definition, that patient is not at his target IOP. At this point, changing or adding to current therapy becomes appropriate, and current markers include noticeable changes to the optic disc appearance, changes to the retinal nerve fiber layer (as seen by the human eye upon fundoscopy or with imaging studies such as SD-OCT), progression of visual field defects, and functional changes of ganglion cells as seen with VEP/ERG studies.

Adding another objective biomarker for the detection of glaucoma progression (especially progression in its earliest form) would have the potential to prove beneficial. I am eager to see if this purported technique can be reproduced in larger scale prospective cohort studies.

The potential for clinical application of such science could lead to a future of glaucoma management that would not only be more effective-but also highly individualistic to each patient.

References

1. Heijl A, Leske MC, Bengtsson B, et al. Early Manifest Glaucoma Trial Group. Reduction of intraocular pressure and glaucoma progression: results from the Early Manifest Glaucoma Trial. Arch Ophthalmol. 2002 Oct;120(10):1268-79.

2. Cordeiro M, Normando E, Cardoso M, et al. Real-time imaging of single neuronal cell apoptosis in patients with glaucoma. Brain. 2017 Apr 26.

3. Quigley HA, Nickells RW, Kerrigan LA, Pease ME, Thibault DJ, Zack DJ. Retinal ganglion cell death in experimental glaucoma and after axotomy occurs by apoptosis. Invest Ophthalmol Vis Sci. 1995 Apr; 36(5): 774–86.

4. Gordon MO, Torri V, Miglior S, Beiser JA, Floriani I, Miller JP, Gao F, Adamsons I, Poli D, D'Agostino RB, Kass MA. Ocular Hypertension Treatment Study Group, European Glaucoma Prevention Study Group. Validated prediction model for the development of primary open-angle glaucoma in individuals with ocular hypertension. Ophthalmology. 2007 Jan;114(1):10–19.

5. Anderson DR, Normal Tension Glaucoma Study. Collaborative normal tension glaucoma study. Curr Opin Ophthalmol. 2003 Apr;14(2): 86–90.

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