Glaucoma as a pathology is a giant puzzle. Making a diagnosis isn’t like diagnosing a cataract, where it is clearly visible with a slit lamp. With glaucoma, there are several metrics we use to determine when to start, escalate, alter or even stop treatment. Glaucoma is a progressive disease, time is one of the key variables.
The general paradigm is to identify a primary open-angle glaucoma (POAG) suspect based on a number of risk factors, monitor for development of POAG, and then treat based on the severity of the disease.
The prevalence of confirmed glaucoma in the United States is approximately 2.56% among adults over the age of 40. However, the number of individuals classified as glaucoma suspects is substantially higher.1
In fact, a retrospective cohort analysis of 83,305 glaucoma suspects between 2007 and 2021 found that 6.1% progressed to open-angle glaucoma (OAG) annually based on International Classification of Diseases (ICD) codes.2 The primary task for all physicians treating patients anywhere on the spectrum of disease: Identify early and reduce risk of progression.
Staging POAG suspects
POAG suspects can be placed into either the low-risk or high-risk category. Low-risk glaucoma suspects carry one to two risk factors, while high-risk suspects have three or more.
Risk factors for development of POAG according to the American Academy of Ophthalmology (AAO) are:3
- Elevated intraocular pressure (IOP)
- Older age
- Family history of glaucoma
- Black race or Latino/Hispanic ethnicity
- Diabetes mellitus
- Lower systolic and diastolic blood pressure
- Lower ocular perfusion pressure
- Myopia
- Thinner central cornea
- Lower corneal hysteresis
- Disc hemorrhage
- Larger cup-to-disc ratio
- Higher pattern standard deviation on threshold visual field testing
Clinical elements to consider when examining glaucoma suspects
Clinically, in addition to elements of a standard dilated comprehensive exam which includes careful stereoscopic optic nerve evaluation, there are five baseline data points I gather at every glaucoma consult:
- IOP
- Corneal thickness or hysteresis
- Visual field (24-2)
- Optical coherence tomography (OCT), specifically retinal nerve fiber layer (RNFL) and ganglion cell analysis (GCA)
- Gonioscopy
Intraocular pressure
Clinically, IOP is the only modifiable risk factor to reduce risk of conversion to POAG from OHT and to slow OAG progression. However, we have to remember IOP is a risk factor, not the pathological component of OAG.
The dependent variable and the disease itself is the loss of axons of retinal ganglion cells. As such, patients can have statistically low IOP with disease, or high IOP without glaucomatous optic neuropathy.
The Ocular Hypertension Treatment Study (OHTS) is a cornerstone of our understanding of ocular hypertension (OHT) and OAG risk. Key findings of OHTS include that untreated OHT patients with IOP at or above 26mmHg combined and central corneal thickness under 555 microns had a 36% risk of development of POAG over 5 years.4
Additionally, untreated OHT patients with IOP less than 24mmHg with pachymetry above 588 had only a 2% risk.4 Clinically, IOP can fluctuate throughout the day. With this in mind, considering “safe” IOP as more of a range rather than a single point is a better strategy in monitoring ocular hypertensive patients.
Corneal thickness and corneal hysteresis
The OHTS also demonstrated that central corneal thickness (CCT) is a risk factor for development of OAG in individuals with OHT.4 The clinical standard for IOP measurement is Goldmann applanation tonometry.5
Tonometry measurements are driven by corneal resistance; as a result, thicker corneas resist more, leading to higher pressure reading. Average corneal thickness is between 520 to 550 microns, however CCT varies.6
Aside from its impact on IOP measurement, corneal thickness may be a biomarker for structural properties of internal structures, specifically the lamina cribrosa. This is foundational for corneal hysteresis—the cornea’s ability to absorb mechanical stress. High corneal hysteresis implies the internal structures may be more capable of handling stress, therefore are more resilient to elevated IOP and progression from OHT to OAG.7
Visual field
Visual field testing is the standard of care for assessing and verifying functional compromise. 24-2 testing, evaluating the central 24 degrees, has been mainstay testing in glaucoma for years. In early disease, 24-2 testing can miss subtle defects, so 10-2 testing may be more beneficial in early stages or when central defects are suspected.
24-2C incorporates 24 degrees with an additional 10 central points from the 10-2 grid, offering a wider range with improved sensitivity. Visual field testing is highly subjective, and therefore can show high variability. In fact, OHTS demonstrated that 85.9% of new visual field defects weren’t confirmed on repeat testing, further emphasizing the need for serial testing on subjects.5
The AAO recommends follow up at least every 12 to 24 months for low-risk suspects, at least every 6 to 12 months for high risk suspects, and at least every 12 months for treated glaucoma suspects when target pressure is achieved.3
Given variability, to establish proper baseline in glaucoma suspects and early OAG patients, visual field testing is recommended to be repeated often; in fact, certain studies suggest up to 6 tests in the first 2 years after glaucoma diagnosis, while recent studies encourage staged or front-loaded testing frequency early in diagnosis.3,8
Optical coherence tomography (OCT)
Along with visual field testing, OCT (both RNFL and ganglion cell layer or complex) imaging can highlight irregularities in structure that correlate with functional damage.
OCT angiography (OCTA) also proves to be a useful tool in detection of structural damage. Early in suspected disease, establishing baselines is critical as imaging can detect change earlier than visual field testing. Metric comparisons of structure over time may show progression faster than typical age progression, suggesting pathological change and warrant initiation of treatment in glaucoma suspects.9,10
Testing should be completed annually at minimum, and like visual field testing, more frequently depending on other factors.3 It's important to not fixate on aged-matched normative databases (“red or green disease”), as this can lead to false positive or false negative interpretation. Instead, clinicians should prioritize serial comparisons over time.
Gonioscopy
An often-overlooked skill, gonioscopy is necessary for accurate glaucoma diagnosis.
Evaluating for the following secondary open-angle features are additional important factors when determining an accurate diagnosis and basis for treatment:
- Angle recession
- Pigment dispersion
- Pseudoexfoliation
- Inflammatory debris
- Risk factors for primary or secondary angle closure, including peripheral anterior synechiae and neovascularization of the angle
Gonioscopy also allows evaluation of the trabecular meshwork pigmentation, which can provide insight into potential selective laser trabeculoplasty response.
Determining a timeline for monitoring glaucoma suspects
Time is a very important factor to consider. As a progressive disease, we need to remember that we can’t recover physical damage to retinal ganglion cell axons.
Guidance from the AAO for follow-up schedule depends on diagnosis and individual risk factors and can generally be described as below:3
- Low-risk suspect: Annual office visit with repeat visual field and OCT testing every 1 to 2 years
- High-risk suspect: Office visit every 6 to 12 months with repeat visual field and OCT testing annually
- Mild glaucoma: Office visit every 6 to 12 months with visual field testing annually
- Moderate glaucoma: Office visit every 4 to 6 months with visual field testing annually
- Severe glaucoma: Office visit every 3 to 6 months with visual field and OCT testing every 6 to 12 months
The frequency of follow up should change based on stability vs. progression. If target IOP range has not been reached or there is progression noted, follow-ups should be appropriate based on treatment method until stability is achieved. It can’t be overemphasized that above is a general guideline and frequency should change based on individual risk factors, severity, and control.3
As stated above, we should consider an increased frequency of visual field testing earlier in the monitoring timeline. Another important aspect of time is the patient's age at time of diagnosis. Younger patients with severe disease would naturally warrant more aggressive monitoring and treatment.3
Initiating treatment in glaucoma suspects
The decision to initiate treatment in glaucoma suspects is made after considering all variables and weighing risk for progressive functional vision loss. Gold standard for treatment, historically, has been topical drops to reduce IOP a certain percentage below its max.
OHTS suggests 20% or more in ocular hypertensive patients, all variables and disease severity must be considered.4 Today, we are seeing a paradigm shift utilizing procedural strategies earlier. Additionally, minimally invasive glaucoma surgeries (MIGS) have armed a wider range of surgeons with the capability of treating glaucoma concomitantly during cataract surgery, or as relatively simple standalone procedures.11
Considerations for topical glaucoma medications
The primary reason we are seeing this paradigm shift is quite simple—the burden of topical eye drops. Several studies show compliance rates are far lower than expected. In fact, one recent meta-analysis looking at over 961,000 patients found that only 44% of patients on once daily dosed prostaglandin analogs were compliant after 1 year.12
On top of this, toxicity to the ocular surface (by the active medication and respective preservatives), medication access, associated costs, and difficulty instilling drops all negatively impact compliance and therefore therapy effectiveness.
As a result, a more proactive, procedural-based mindset has become an increasingly popular strategy among glaucoma specialists in an attempt to reduce compliance issues and maintain better control.10
The paradigm shift to interventional glaucoma management
A secondary reason for this trend is ease of access. The relative simplicity of MIGS procedures compared to traditional glaucoma surgeries has allowed cataract surgeons the ability to surgically treat patients with quick, safe, and effective procedures at the same time as cataract surgery.
Glaucoma surgery previously was exclusively in the domain of the glaucoma specialist. Additionally, studies have shown that selective laser trabeculoplasty (SLT) is a very safe and effective treatment that can be completed by general ophthalmology (and optometry now in several states) in office.13
5 key takeaways
- Glaucoma is a puzzle: We must gather several pieces of data early in the process of monitoring POAG suspects to establish baselines and determine next steps.
- Risk drives follow-up: Multiple risk factors for development of POAG, not just one, should determine follow-up schedule of glaucoma suspects.
- Structure and function should tell a similar story: Don’t fall into the trap of “red” or “green disease.” Structural change precedes functional change (in most cases) however both should tell a similar story.
- IOP is a risk factor, not the disease itself: While setting a target IOP is important in management, the IOP is the controllable variable. The disease is about damage to nerve fibers. It’s important to consider all variables when deciding if treatment is necessary in glaucoma suspects and ocular hypertensive patients.
- Earlier intervention is changing glaucoma care: Adopting an interventional mindset ensures adequate sustained IOP control while reducing burdens of topical therapy.
In closing
There’s no standard algorithm for managing a glaucoma suspect. Cumulative information must be gathered over time and weighed against individual patient risk factors. By integrating structural and functional testing with careful clinical evaluation, clinicians can confidently make informed decisions on if, or what type of, treatment should be initiated.
