Making Headway in the Treatment of a Common Disease

From Hans Goldmann’s invention of the bowl perimeter in 1945, to his development of the applanation tonometer in 1950, to the introduction of timolol maleate in 1978, clinicians and scientists have taken meaningful steps forward over the decades toward halting vision loss from glaucoma.^1,2 Now looking forward into 2021, the foundation is set for even better diagnostics, more effective pharmaceutical treatments, and safer procedures to allow us to intervene sooner in the disease process, potentially preserving more of our patients’ vision and quality of life. (See COVID-19 Considerations for additional factors eye care practitioners may need to give thought to in the coming year.) Let’s take a look at some of what’s new and what’s to come.

DATA, DIAGNOSIS, OUTCOMES: STRONGER, FASTER, BETTER

A New Approach to Tonometry

Goldmann applanation tonometry (GAT) is the mainstay of glaucoma monitoring, as IOP remains the central modifiable risk factor to reduce the effects of glaucoma. For going on 70 years, measurement with GAT has been the standard, but the CATS Tonometer Prism (CATS Tonometer) now shows promise for measuring a more accurate “true IOP” (Figure 1).

The CATS tonometer slides into an existing Goldmann apparatus and looks similar to the familiar device, the difference being the sinusoidal curved applanation surface that comes into contact with the cornea. This geometry optimizes centration and minimizes confounding factors such as corneal thickness, hysteresis, and tear film interaction.³ The results of multicenter randomized controlled trials have been promising, showing improved accuracy in direct comparison to GAT and to intracameral pressure as measured by transducer.^3,4

A New Optic Nerve Measurement

For objective assessment of the optic nerve tissue, OCT measurements of the circumpapillary retinal nerve fiber layer (RNFL) and macular ganglion cell complex (GCC) have been the gold standard of the past decade. A new measurement of the neuroretinal rim, called the Bruch membrane opening (BMO) minimum rim width (MRW) is now being studied as a method of identifying glaucoma. This measurement is taken at the optic nerve, measuring the distance from the opening of Bruch membrane to the internal limiting membrane (ILM) (Figure 2).

BMO is a stable reference point, and change in the MRW over time has shown a stronger association with visual field sensitivity and glaucoma discrimination than RNFL thickness in some studies.^5,6 In particular, when high myopia, epiretinal membrane, or other macular pathologies are present, BMO-MRW may be particularly useful.⁷

Until we know more, it is likely best to use all three measurements—RNFL, macular GCC, and now the optic nerve head—for the most accurate diagnosis of early glaucoma damage, for those who have the capability. The BMO-MRW measurement is available on Spectralis (Heidelberg Engineering) OCT instruments.

A New Perimetry Protocol

The main reason to treat glaucoma is to prevent functional vision loss, and the all-important visual field exam is our principal method of monitoring function. The ideal perimetry test is fast, accurate, and highly repeatable, and patients and clinicians alike long for improved options. Cue the 24-2c SITA Faster (Carl Zeiss Meditec), a test protocol that is approximately 20% shorter in duration than the 24-2 SITA Fast and at the same time adds 10 central points to the 24-2 pattern for better detection of central scotomas.⁸

These improvements do come with a tradeoff, including no false negative checks and no blind spot catch trials, so a compliant and attentive patient is needed to obtain optimal results. That said, studies have shown SITA Faster’s diagnostic performance to be noninferior to that of SITA Standard and SITA Fast testing.⁹

SAFER TREATMENTS

Choosing SLT

First-line treatments for glaucoma have traditionally included topical medications and laser trabeculoplasty in theory. In practice, however, a recent survey found considerable reluctance to use selective laser trabeculoplasty (SLT) as a first treatment option.¹⁰ The LiGHT trial reaffirmed the safety, efficacy, and cost-effectiveness of SLT as a first-line therapy, demonstrating a higher percentage of patients achieving target IOP and fewer patients requiring subsequent glaucoma surgery with SLT than with medical treatment over a 3-year follow-up period.¹¹

In my glaucoma clinic, I routinely offer SLT and eyedrops as options for primary treatment. I outline the pros and cons of each, and usually the patient is the decider. Motivating factors appear to be convenience and the avoidance of prostaglandin periorbitopathy and ocular surface issues, especially in young and active patients.

Excellent results can be achieved with 360° treatment in mildly to moderately pigmented trabecular meshwork; however, 180° treatment is prudent in patients who have pigmentary dispersion syndrome to limit the possibility of a transient spike in IOP.^12,13 It is important to discuss the duration of SLT effect with patients, as it is a useful treatment but not a cure. I tell patients that it works well for about 75% of those who choose this option, and that the effects last 2 to 4 years. Regular follow-up and testing are necessary regardless of the patient’s treatment choice.

Improving Medical Treatment

When IOP remains above target despite treatment with a prostaglandin analogue, additional medical therapies are often the answer. Adjunctive drugs have traditionally required multiple daily dosing and can have a detrimental effect on ocular perfusion pressure.¹⁴ A relatively new once-daily alternative is netarsudil and latanoprost ophthalmic solution 0.02%/0.005% (Rocklatan, Aerie Pharmaceuticals). This fixed-combination drop includes netarsudil, a novel rho-kinase inhibitor targeting the traditional outflow pathway of the trabecular meshwork.¹⁵

In the MERCURY-2 trial, more than twice as many patients treated with netarsudil/latanoprost achieved at least a 30% reduction in IOP compared with those treated with latanoprost alone.¹⁶ The complementary mechanisms of targeting both the trabecular meshwork and the uveoscleral pathway with once-daily dosing make this an ideal medication to substitute when latanoprost alone is insufficient, and it also pairs well with an aqueous suppressant fixed combination for maximum nonsurgical IOP control.

The most common side effect to prepare patients for is mild hyperemia. When patients are notified that this may happen ahead of time, it is less likely to be an issue, and when discussed in the context of possible vision loss and surgery, patients are often grateful for an easy solution.

Improving Surgical Treatment

When laser and topical therapies fail, surgery is indicated. Historically this would have been by means of a high-risk/high-reward, bleb-based surgery, an option that may be excessive when only modest IOP lowering is needed. In recent years, several less invasive surgical options, grouped under the heading of microinvasive glaucoma surgery, or MIGS, have emerged. Examples include the iStent inject (Glaukos), the Hydrus Microstent (Ivantis), and the newest to the scene in the United States, the angle-based Omni Surgical System (Sight Sciences). The Omni is a viscodilation and trabeculotomy procedure (Figure 3) that maintains a better safety profile than bleb-based procedures.

The Omni Surgical System’s FDA clearance allows it to be used in combination with cataract surgery or as a standalone procedure; the other procedures are indicated for use only in combination with cataract surgery. Postoperative hyphema and steroid response with the Omni are generally mild and transient. Mild peripheral anterior synechiae formation can limit IOP control in a minority of cases. In patients with a baseline medicated IOP of more than 18 mm Hg, the Omni demonstrated a mean decrease of 26% (approximately 6 mm Hg), and a decrease from 1.7 medications to 1.2 at month 12.¹⁷ The Omni appears to be an ideal mitigating procedure in offering excellent results, minimal relative risk of complications, and preservation of precious conjunctiva for bleb-related procedures in the future, if necessary.

IN IT FOR THE LONG HAUL

The journey to curing glaucoma is long, but we are gaining speed. With new technologies, safer treatments, and continued ingenuity, our patients will be the better for it.