Article

From Art to Science in DME Treatment

A comparison of anatomical outcomes following navigated OCT-based laser and conventional focal laser treatments

From Art to Science in DME Treatment

A comparison of anatomical outcomes following navigated OCT-based laser and conventional focal laser treatments

ANG LI, BA • RUMNEEK BEDI, BA • RISHI P. SINGH, MD

The complicated and prolonged cases that retinal physicians are often dealt mean that the appropriate treatment of diabetic macular edema frequently presents a challenge, even today.

However, the simple fact that DME is one of the most common causes of visual loss in the working-age population highlights the importance of finding the safest and most effective method of treatment.

Intravitreal anti-VEGF injection therapy has widely replaced focal laser photocoagulation as the first-line therapy due to faster and significant improvements in vision.

At the same time, it is important not to underestimate the value of laser treatments for their durability of results, proven in more than three decades of clinical experience and also in the light of new technological advancements.

Visual features, such as digital mapping and navigation, OCT image import, and eye tracking, offer us a valuable tool set to improve our treatment of DME using photocoagulation, for example, when it comes down to anatomical changes.

WHY LASER?

According to the Early Treatment Diabetic Retinopathy Study, laser photocoagulation treatment for clinically significant DME was shown to reduce the chances of visual loss in about 51% of cases, but only 10% of patients demonstrated visual improvements.1

In contrast, anti-VEGF therapies have shown some of the most promising results, with improvements in VA and anatomical changes.2-6 Is there still a need for a better paradigm?

Ang Li, BA, and Rumneek Bedi, BA, are medical students at the Cleveland Clinic’s Lerner College of Medicine in Ohio. Rishi P. Singh, MD, is a staff physician at the Cole Eye Institute of the Cleveland Clinic. He reports no financial interest in any of the products mentioned here. Dr. Singh’s e-mail is singhr@ccf.org.

Anti-VEGF therapies have their limitations as well. For one, they cannot alleviate macular hypoxia. Additionally, injection therapy requires frequent injections over extended periods, prolonging the treatment burden for patients and raising doubts as to whether trial results can be duplicated in everyday clinical practice with real-life patient compliance. It is also important to note that not all patients respond to anti-VEGF therapies by gaining vision, and some may even lose vision.7

Finally, while the side effects are relatively rare, they do exist. Some of the potential adverse effects of anti-VEGF therapies include issues surrounding wound healing, arterial thromboembolic events, dyspnea, stroke, and endophthalmitis.

If delivered correctly, laser treatments can successfully reduce retinal hypoxia and neovascularization stimuli, and they can be used to target very precise areas on the retina.

Why Not Laser?

It seems appropriate to ask why laser therapy has not really been considered successful in providing effective results for the treatment of DME patients, particularly in terms of the visual outcomes.

Laser treatments were shown to fail to provide vast improvements in vision in various multicenter trials, in which the mean BCVA change at least one year postoperatively ranged between 3 and -4.6 letters.8-10

In fact, between 8% and 26% of patients experienced a loss of three lines of vision following laser treatment. So why does laser appear to fail in the treatment of DME patients?

Some of the disadvantages of conventional laser treatments include poor laser uptake and poor targeting of areas of thickening, as well as variable and incomplete treatment. In a moving patient, it can prove especially challenging to target specific locations of edema, which can be quite difficult to visualize.

All of these obstacles contribute to the inefficacy of laser treatments for DME patients. However, it is a common error to group laser treatments into a single category, in which we generalize the outcomes of different types of laser treatment. If we distinguish between the different types of laser treatment, we can see more diversity in the outcomes of treated patients, for example, in terms of anatomical differences.

Laser may be particularly effective in patients who have not yet lost vision due to foveal involvement of DME, as well as in patients who have recovered vision after successful anti-VEGF therapy.

OCT-BASED NAVIGATED LASER TECHNOLOGY

Many of the limitations of laser treatments highlighted above are associated with conventional focal laser treatment. Newer technologies have sought to address these issues, such as the OCT-based navigated laser, which enables physicians to plan laser treatments digitally, to ensure accuracy and repeatability.11 Much of this planning is based on imaging and multimodal registration, which facilitate improved treatment planning and targeting capabilities.

A study presented last year at the annual meeting of the Macula Society demonstrated that an entire area of edema fed by a single microaneurysm (known as SALMO patches, or significant actively leaking microaneurysms on OCT) could be treated effectively when targeting the microaneurysm with a laser.12

With a conventional focal laser, the photocoagulation process involves the physician manually shining a single ray of the laser on the nonfoveal retina, which is plagued with microaneurysms and surrounding areas of edema. The exact area of a leaking microaneurysm is not immediately identifiable when observing through the slit lamp without the aid of an angiogram.

With a navigated laser, the physician has the benefits of greater customizability, programmable grids, and real-time navigational guidance through the retinal topography, which enables him or her to implement a more accurate laser treatment to specific targets of microaneurysms identified on an angiogram that is aligned and overlaid on the living retina.

It also allows the doctor to overlay a live fundus image atop a previously obtained OCT image, allowing for excellent digital visualization of the retina that enables the mapping and monitoring of retinal changes associated with diffuse macular edema more effectively.

Additionally, eye-tracking technology in navigated lasers improves safety, by prepositioning the aiming beam and deactivating the laser during incidences of misalignment.

By addressing the setbacks of conventional focal lasers, navigated laser technology offers a compelling solution to the laser problem, through digital planning, visualization, and targeted laser delivery.

CLINICAL EXPERIENCE

In our retrospective analysis of patients with clinically significant DME, my colleagues and I evaluated the anatomic outcomes of application using OCT-based navigated laser vs traditional focal laser photocoagulation in DME patients.

In the study, 21 patients underwent OCT-based navigated laser treatment with the Navilas Laser System (OD-OS, Irvine, CA).

In the comparator arm, patients who had undergone focal treatment without OCT guidance with a traditional slit lamp-based system (Iridex, Mountain View, CA) were evaluated.

Anti-VEGF injections were delivered if needed, at least one month after laser photocoagulation. For the conventional laser group, chart reviews were performed for patients who met the same inclusion and exclusion criteria as the prospective group of patients, to ensure adequate comparison.

In terms of outcome measurements, central subfield thickness, cube average thickness, and cube volume were assessed over time using OCT. The navigated laser approach resulted in a greater reduction in central subfield thickness than conventional laser treatment after one month (Figure 1).

Figure 1. A comparison of average central subfield thickness (µm) between patients receiving Navilas laser therapy and conventional focal laser treatment, showing greater reduction in the Navilas group

Between baseline and one month, no injections needed to be administered. Between the first and third months, two of 21 patients in the navigated laser group required an injection, compared to 16 of 27 in the conventional laser group, which indicated a reduced injection burden in clinical practice with the navigated laser approach.

Case Study

Homing in on an individual case, a patient came to our clinic with nonproliferative diabetic retinopathy with clinically significant macular edema in the left eye. The patient had previously had focal laser treatment in this eye, and the fluorescein angiography we performed showed mild ischemic changes within the fovea and no evidence of neovascularization elsewhere (Figure 2).

Figure 2. Pre-Navilas treatment fluorescein angiography of a case, showing mild ischemic changes within the fovea of a patient with clinically significant macular edema

At our clinic, the patient received OCT-based navigated laser treatment in the left eye (Figure 3). Six months after the treatment, the presence of macular edema was reduced significantly, and the patient’s VA demonstrated stability at 20/40 (Figures 4 and 5, page 44).

Figure 3. The Navilas treatment plan.

Figure 4. Pre-Navilas treatment OCT image and retinal thickness map showing significant macular edema in the foveal region.

Figure 5. An OCT image and retinal thickness map from six months after Navilas treatment showing that edema was reduced significantly.

CONCLUSION

There is a broad spectrum of types of DME, each of which demands a different mode of treatment, whether it is with anti-VEGF therapies, photocoagulation, or a combination of both. As physicians, our overall goals are to treat DME, to maintain our patients’ vision successfully, and to reduce the burden on our patients.

In our hands, the OCT-based navigated laser approach has helped to improve outcomes and decrease treatment burden. Overall, it has enabled us to improve the accuracy and reproducibility of laser treatments, and it appears also to have improved retinal thickness outcomes to the level of anti-VEGF therapies (although further study is warranted).

Perhaps most importantly, the navigated laser approach allows us to target microaneurysms precisely and effectively, while compensating for inadvertent eye movements and increases the likelihood that we will deliver the full laser treatment indicated for each patient.

As with other technological advancements, navigated laser helps us standardize DME treatment, building on what had previously been more of an art, allowing more of us to deliver the results we aspire to achieve for our patients. RP

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