The death of retinal ganglion cells (RGCs) is what leads to glaucoma-induced vision loss. The more RGCs that die, the worse vision loss becomes. As RGCs are part of the central nervous system, they do not regenerate once lost. However, death is the final step in the process. If an eye care professional can identify when RGCs begin to stop working properly due to increased intraocular pressure, treatment can begin at this early stage, thus slowing or preventing cell death and vision loss.
Glaucoma is characterized by damage to the optic nerve head (ONH), which is the exit point for fibers of retinal ganglion cells (RGC).1 The ONH bears pressure from the eye wall and facilitates circulation of blood within the eye. Abnormal changes to the ONH, most visibly the thinning of the ONH’s neuroretinal rim, along with optic disc hemorrhaging and cupping are among the first glaucomatous characteristics that develop due to intraocular pressure and/or the loss of fluid circulation.1 This blocks the circulation of fluid to RGCs, which subsequently leads to RGC damage, followed by RGC atrophy and death.
Early Signs and Symptoms
The true time of disease onset for glaucoma is the stage where RGCs become damaged, before vision loss develops. Visual field testing and optical coherence tomography (OCT) are typically unable to detect early ganglion cell damage at this point and instead detect cell atrophy and death; a stage at when vision impairment is irreversible. In fact, the death of approximately 30% of RGCs must happen before it becomes evident on even advanced visual field tests.2
Once vision loss occurs due to glaucoma, it cannot be restored through currently available treatments. Therefore, early detection of RGC abnormalities before cell death and vision loss takes place is the key to delaying the progression of this disease through therapeutic approaches.
Now that visual electrophysiology has been embraced by mainstream eye care clinicians, objective, functional testing of RGCs is easier than ever. There are two types of electroretinography (ERG) tests that record subtle alterations in the electrical responses of the RGC layer, identifying dysfunction before the cells atrophy and die. In doing so, these tests improve a doctor’s ability to identify early damage from glaucoma and make informed, timely diagnoses and management decisions.
PERG has demonstrated the ability to accurately detect changes in RGC function that reflect the early onset of glaucoma.3 A study conducted at the Bascom Palmer Eye Institute demonstrated that PERG signals were able to anticipate an equivalent loss of RNFL as seen on OCT on average 8 years sooner.4 Another study showed that alterations in PERG signal—which are discernable in eyes of patients at risk for progression from suspected to manifest glaucoma—precede losses of visual field and optic nerve tissue. The authors noted PERG alterations can be reversible after IOP lowering, showing a strong correlation between the test and functional loss secondary to glaucoma.5,6
Example Diopsys® ffERG / Flash Plus Photopic Negative Response waveform of a healthy patient.
Another modality that is useful toward identifying early stages of this disease involves the use of full field ERG to evaluate the photopic negative response (PhNR). The PhNR is the negative-going wave following the b-wave that originates from the RGCs and their axons.7 As the PhNR can be reduced in disorders that affect the innermost retina, including glaucoma and other forms of optic neuropathy, it is a beneficial biomarker for early detection.8,9
Therapeutic approaches that delay the progression of glaucoma are available, but early detection is critical to save vision. Several traditional practice-based tests found in eye care offices have proven ineffective at identifying retinal ganglion cell dysfunction before atrophy and death occurs.
Technologies such as PERG and ffERG with PhNR have demonstrated the ability to accurately detect RGC damage from glaucoma before cells die.1-9 To prevent retinal ganglion cell death, eye care professionals should consider these advanced approaches for identifying and combating this debilitating disease.
1. Bourne RR. The optic nerve head in glaucoma. Community Eye Health. 2006;19(59):44-5. 2. Broadway DC. Visual field testing for glaucoma - a practical guide. Community Eye Health. 2012;25(79-80):66-70. 3. Good P. Shifting patterns in glaucoma management: Earlier diagnosis, more timely intervention and more rational clinical decisions: the advantages of steady-state pattern electroretinography should not be ignored. https://theophthalmologist.com/subspecialties/shifting-patterns-in-glaucoma-management 4. Banitt MR, et al. Progressive Loss of Retinal Ganglion Cell Function Precedes Structural Loss by Several Years in Glaucoma Suspects. Invest. Ophthalmol. Vis. Sci. 2013;54(3):2346-2352. 5. Porciatti, V, and Ventura, L. The PERG as a Tool for Early Detection and Monitoring of Glaucoma. Curr Ophthalmol Rep (2017) 5:7–13. 6. Derr P, et al. Retinal Ganglion cell Functional Recovery After IOP lowering treatment in Glaucoma Suspects. Poster presented at: ARVO; 2019 Apr 28-02; Vancouver, B.C. 7. Kim HD, Park JY, Ohn YH. Clinical applications of photopic negative response (PhNR) for the treatment of glaucoma and diabetic retinopathy. Korean J Ophthalmol. 2010 Apr;24(2):89-95. 8. Drasdo N, Aldedasi YH, Chiti Z, et al. The s-cone PHNR and pattern ERG in primary open angle glaucoma. Invest Ophthalmol Vis Sci 2001;42:1266-72. 9. Frishman L, et al. ISCEV extended protocol for the photopic negative response (PhNR) of the full-field electroretinogram. Doc Ophthalmol. 2018;136:207-211.