Evaluation of a Novel, Non Contact, Automated Focal Laser with Integrated (NAVILAS) Fluorescein Angiography for Diabetic Macular Edema.

PURPOSE: To evaluate the procedural experience and complications of a novel integrated laser delivery system (NAVILAS(®); OD-OS Teltow, Germany) that combines automated laser delivery with color fundus photography, fluorescein angiography (FA), fundus autofluorescence (FAF) and infrared imaging with a frequency doubled YAG laser.
MATERIALS AND METHODS: This prospective study evaluated surgical experience with the NAVILAS automated photocoagulation system for the treatment of patients with diabetic macular edema (DME). Subjective assessment of the accuracy of laser spot placement and postoperative complications were documented.
RESULTS: Twelve patients (7 males, 5 females) were enrolled in this pilot study. Five patients were phakic and 7 were pseudophakic. Image overlays and the tracking system allowed accurate delivery of laser spots of varying size, duration and power. None of the patients reported any pain and tolerated the procedure well. No complications were reported in the study.
CONCLUSION: In this pilot study, the NAVILAS system allowed accurate laser spot placement with no complications in patients with DME. However a larger sample with longer follow up is required to determine the safety of this procedure.

INTRODUCTION

In developed countries, diabetic macular edema (DME) is a leading cause of blindness in individuals below 65 years of age.1–4 DME often results from focal leakage of microaneurysms or diffuse leakage across dysfunctional retinal pigment epithelium (RPE).1–4 DME is confirmed by leaking microaneurysms on fluorescein angiography (FA) and/or areas of dysfunctional RPE.5–7 Focal macular photocoagulation with a green wavelength laser is used to seal the leaking microaneurysms and alleviate macular edema.67

The FA is used to localize the microaneurysms for laser treatment. However this is a subjective method involving visual assessment and comparison of the FA to the retina during treatment. This subjectivity may result in areas that are missed during laser treatment and in rare cases, overtreatment. Furthermore, the use of inappropriate laser settings, the lack of patient cooperation and ocular saccades can result in foveal burns, retinal hemorrhages due to rupture of microaneurysms, development of choroidal neovascular membranes and subretinal fibrosis.8–10

Eye-tracking technology enables precise real-time point-to-point correlation between the retinal pathology and the fundus images, and allows repeat scans of critical areas during treatments.1112 The addition of eye-tracking during laser photocoagulation (similar to laser in situ keratomiluesis) will likely improve the safety and accuracy and reduce the complications associated with retinal photocoagulation.

A system that combines eye-tracking with laser photocoagulation has recently become commercially available. The NAVILAS® photocoagulation system (OD-OS Teltow, Germany) is an integrated system that combines color fundus photography, FA, fundus autofluorescence (FAF), and infra-red imaging (IR) with a target locked frequency-doubled YAG laser. Conceptually, the NAVILAS system is designed for accurate treatment of clinically relevant leaking microaneurysms and to minimize treatment time. A recent study that compared NAVILAS to conventional laser reported 20% greater accuracy with the NAVILAS system compared to conventional laser (92% hit rate vs.72% hit rate, respectively).13 Ocular saccades are compensated to ensure that the laser spot is delivered to the intended area.

In this pilot study, we subjectively evaluated the accuracy and complications of the NAVILAS system for focal macular laser photocoagulation for DME.

MATERIALS AND METHODS

This was a pilot study evaluating the clinical use and complications of the NAVILAS laser in 12 patients undergoing focal macular laser for DME. The NAVILAS system [Figure 1] includes functions such as, an image and treatment plan overlay, target assistance, and the ability to preposition the aiming beam of the laser system. It uses a continuous wave, potassium titanyl phosphate, diode-pumped frequency-doubled solid state Nd:YVO laser in the infrared range, that is transformed with a frequency-doubling element.

Figure 1

Photograph of the NAVILAS system with the monitor illustrating the no-treatment zones marked with a circle and a strike through within the area. White spots are the areas identified by the surgeon for treatment and the yellow pattern spot is one of the preset patterns available for use for laser delivery

Informed consent was obtained from each patient. To prevent selection bias, all consecutive patients who presented to the laser clinic over two days were enrolled. Patients underwent a full ophthalmic examination including slit-lamp biomicroscopy of the anterior segment and measurement of the intraocular pressure by applanation tonometry. Prior to laser photocoagulation, fundus examination was performed at the slit lamp with a +78 D lens to confirm the presence of macular edema. All patients underwent fundus photography (Zeiss FF450, Carl Zeiss, CA, USA), infrared and fluorescein angiography (Spectralis, Heidelberg Engineering, CA, USA). During FA, 3 cc of 10% fluorescein was administered through the antecubital veins. Early and late phase fluorescein angiographs were obtained.

The difference in treatment algorithms between conventional photocoagulation and the NAVILAS laser is outlined in Figure 2. Treatment planning was performed with the real-time IR or FA images. Areas that leaked and the associated microaneurysms were marked. Various treatment parameters and patterns such as rectangle, ring and arc were selected for focal macular laser delivery [Figure 3].

Figure 2

Convention flow diagram versus the new NAVILAS machine in treating patients with macular edema. Note that there is no requirement for use of contact lens for patients treated with NAVILAS laser

Figure 3

Different preset parameters for spot number, spot size and spot spacing available on NAVILAS for focal macular laser

All treatments were performed by one retinal surgeon. Topical anesthesia (proparacaine hydrochloride ophthalmic solution 0.5%, Akorn Inc., Lake Forest, Illinois, USA) was instilled in the inferior fornix of the treatment eye. The image was obtained and the treatment plan digitally overlaid on the screen. A previously acquired image (FA or IR image) or optical coherence tomography (OCT) was used to identify the areas that required focal laser treatment. The treatment plan designated the treatment areas and the protected or non-treatment zones such as the optic nerve and fovea. The treatment plan was superimposed on the IR or FA image for easy correlation of the landmarks and targets. “Target assistance” was used to lock the position of the laser to compensate for eye movements. Laser delivery was initiated by depressing a foot pedal. Prepositioning allowed the user to direct the laser to the previously planned target and advance to the next area and so on. A planned algorithm was completed automatically in a sequential fashion. Typical images are displayed in Figures 4 and 5 (non-contact). A contact lens was not required for laser delivery. The user could switch to a color image to evaluate the quality of the burn and adjust the laser settings. Laser delivery could be stopped at any time by releasing the foot pedal. The system provided a spot documentation marker that detected successful laser application that could be referenced postoperatively to identify areas which previously underwent sub-threshold treatment.

Figure 4

(a) Color fundus photo of the left eye of a study patient with DME. (b) Infrared photo of the left eye of the same patient. (c and d) Represent early and late fluorescein angiogram of left eye of the study patient. (e) An image overlay is composed and displayed over a previously acquired image showing planning elements and no-treatment zones. (f) Treatment is given to the left eye using the NAVILAS laser. (g) Color fundus photo of the left eye after NAVILAS laser is delivered

Figure 5

(a) Color fundus photo of the right eye with evidence of a patient with diabetic macular edema. (b) Infrared photo of the right eye of the same patient. IR image highlights the collection of hard exudates. (c) An image overlay is composed and displayed over a previously acquired image showing planning elements and no-treatment zones (NTZ). NTZ are marked as crossed lines over the foveal avascular zone and optic nerve head. (d) Treatment is given to the right eye using the NAVILAS laser. E. Color fundus photo of the right eye after NAVILAS laser is delivered

The treatment areas were imaged with spectral-domain optical coherence tomography (Spectralis, Heidelberg Engineering, CA, USA) preoperatively and postoperatively [Figure 6]. Chart review was performed for patient discomfort and clinical evaluation of lens damage or burns to the optic nerve or fovea.

Figure 6

Pre and post cross-sectional image on spectral-domain OCT (spectralis) of a patient in the study who underwent focal macular laser on NAVILAS for DME. Cross-sectional image reveals thickening of the inner plexiform and inner nuclear layer. Postlaser images reveal the laser track down to the retinal pigment epithelium

RESULTS

The study cohort comprised of 7 men and 5 women. The average age of the cohort was 60 years (range, 42–73 years). Five patients were phakic and seven were pseudophakic. The average visual acuity prior to laser therapy was 0.40 logMAR (Snellen 20/40; range, 0 logMAR to 1.9 logMAR).

Ten patients had undergone prior treatment for DME which included focal macular laser, anti-vascular endothelial growth factor therapy with intravitreal bevacizumab, intravitreal steroids and/or pars plana vitrectomy. None of the patients reported any pain during the procedure. The average number of laser spots was 73 per session (range, 6 to 186 spots).

The average preoperative central macular thickness was 360 μm. All patients tolerated the procedure well and no complications were noted. There was no notable damage to the physiologic lens or intraocular lens implant postoperatively. There was no evidence of foveal burn or inadvertent laser delivery to nontargeted areas in any patient undergoing NAVILAS treatment.

Postoperative evaluation using FA and color fundus photography confirmed point-to-point correlation of the spots selected by the surgeon to the spot placement by the laser. The tracking system compensated for eye movements or changes in head position which allowed accurate laser delivery. The machine temporarily suspended the laser delivery if the ‘live retinal image’ did not overlap with the FA or fundus image.

DISCUSSION

The outcomes from the Early Treatment Diabetic Retinopathy Study (ETDRS) confirmed the efficacy of focal macular laser in the management of clinically significant macular edema.6 However, 25% of treated eyes in the ETDRS still had retinal thickening at 3 year follow up.7 Additionally, complications from laser burns, including progressive increase in laser scars and formation of choroidal neovascular membranes, have been reported.8–10 Studies evaluating the use of lower threshold burns to minimize complications have reported decreased efficacy of treatment.1415 The NAVILAS system is an innovation aimed at simultaneously minimizing treatment complications and maximizing the efficacy of focal macular laser treatment.

The image overlay and tracking systems allow the surgeon to accurately deliver laser spots of varying size, duration, and power guided by FA and/or fundus photography. Areas of pathology selected for laser photocoagulation on FA/fundus photography correlate directly to the laser spot placement. Each individual spot can be monitored easily by toggling between the laser delivery screen and the ‘live’ color image of the fundus. This allows for greater efficiency and safety for the surgeon and the patient. For enhanced safety, laser restriction (foveola and optic nerve) zones are established.

The laser pattern can be customized for a surgeon based on spot size, power and duration. Using FA and a fundus photograph, a customized treatment can be planned prior to laser delivery to the eye. This pattern is saved and an overlay is available to monitor treatment at follow-up visits. Additionally, grid patterns of different shapes are available and can be individually tailored to the clinical setting. In addition to patient safety, the greatest potential application of this laser technique is the ability for standardization of a laser protocol that can be used in multi-center retinal laser trials.

We successfully evaluated safety in 12 patients with DME. Postoperative evaluation confirmed point-to-point correlation of the areas selected for treatment by the surgeon to the laser spot placement by the NAVILAS system. Similar results have been reported by Kozak et al.,13 who noted that in their series of 25 consecutive patients who underwent focal macular laser for various macular pathologies, laser delivery was very accurate compared to the treatment plan. The tracking system allowed accurate laser spot delivery through compensatory motion to counteract the eye movements and changes in head position. As a safeguard, laser delivery is temporarily stopped when the retina does not overlap the FA or fundus image.

None of the study patients reported any pain or discomfort during the procedure. Unlike the contact lens based delivery of conventional laser systems, NAVILAS uses a non contact fundus platform for laser delivery, increasing patient comfort. In addition, use of the IR setting during the procedure minimizes light exposure, further enhancing patient cooperation. We anticipate the low resolution of FA images from the NAVILAS system will be a major disadvantage. Further comparative studies are warranted to analyze any differences in FA images performed with the NAVILAS system and digital scanning laser ophthalmoscope-based platforms.

Data on functional outcomes including correlation with retinal morphology on spectral-domain OCT at various time points following the laser treatment, could have added considerable strength to the study design. Future advances of this technology may include incorporation of a module for pan-retinal photocoagulation. Other clinically useful additions would be the incorporation of spectral-domain OCT and microperimetry to provide histological and functional correlation over time. We anticipate that the disadvantages of this machine include difficulty with moderate and dense cataracts, the cost and the lack of long term follow up on this unit. Drawbacks of our study include the lack of follow up data and the sample size. However this was our initial experience with this novel laser, hence caution dictated the selection of a small group of patients.

In conclusion, initial results from our pilot study reveal that NAVILAS is a unique laser delivery system which provides a laser safety zone to protect the foveal avascular zone and incorporates point to point correlation of surgeon directed laser spots on real time FA and/or color fundus photography, affording the retinal surgeon the ability to safely deliver laser spots to the retina without the use of a contact lens.