Purpose
To compare the clinical efficacy of navigated pattern and conventional slit-lamp pattern panretinal photocoagulation (PRP).
Design
Randomized clinical trial.
Methods
Seventy-four eyes with proliferative diabetic retinopathy (PDR) in need of PRP were randomly assigned to 1 of 4 groups: PRP conventional pattern 30 ms, 100 ms, navigated pattern 30 ms, 100 ms pulse. Navigated laser is a fundus camera–based photocoagulator with retinal eye tracking. Outcome variables included stability of visual acuity, regression or development of neovascularization and need for retreatment sessions and surgical intervention, pain perception, and procedure time.
Results
There was no change in visual acuity between pre- and post-treatment measurements among the study groups. Short pulse groups in total required 22 procedures compared to 12 procedures in long pulse groups ( P < .05). A trend toward worse outcome using 30 ms pulse duration treatments is expressed by slightly increased relative risk of 1.3 compared to 100 ms groups. Only 2 eyes required vitreoretinal surgery for nonclearing vitreous hemorrhage, 1 in each 30 ms group; insignificantly different between study groups ( P = .98). The pain score was lower with navigated laser as compared to conventional laser in both 30 ms groups ( P = .1) and 100 ms groups, where it reached statistical significance ( P = .02). Pain experience was significant ( P < .001) between navigated 100 ms pattern and conventional single-spot 100 ms treatments.
Conclusions
This study demonstrates better clinical efficacy of 100 ms compared to 30 ms treatments using both conventional and navigated pattern lasers. The ability to use long-pulse-duration navigated pattern treatments broadens therapeutic options for PRP in proliferative diabetic retinopathy.
Laser panretinal photocoagulation (PRP) is effective for the treatment of proliferative diabetic retinopathy (PDR). The Diabetic Retinopathy Study (DRS) and Early Treatment Diabetic Retinopathy Study (ETDRS) established standardized treatment with parameters of 200–500 μm spot size and pulse duration of 100–200 milliseconds (ms) and power to produce moderate-intensity burns. This procedure is continued peripherally to achieve a total of 1200–1600 applications over 2–3 sessions. The ETDRS protocol represents the current gold standard for treating PDR.
The introduction of pattern scanning laser systems such as PASCAL (Topcon Medical Laser Systems, Inc; Tokyo, Japan) allow delivery of various predetermined laser spot patterns that significantly reduce treatment time and the patient’s perception of pain. However, this improvement requires a reduction of the pulse duration to 10–30 ms, which deviates from the ETDRS protocol. This reduction in pulse duration is required to respect the eye movements that occur while the laser pattern is applied to the retina. Some have speculated that the reduced effectiveness of pattern scanning laser compared to conventional laser photocoagulation for cases of neovascularization is attributable to this reduction in pulse duration. Others have suggested adjustment of the treatment parameters to compensate for the reduced efficacy in neovascularization.
In 2009, fundus camera–based navigated laser photocoagulation with retinal eye tracking (NAVILAS; OD-OS GmbH, Berlin, Germany) was introduced. Initial studies established its role in focal treatment. However, this laser technology has several navigation functions for panretinal laser treatment, including imaging and the delivery of single and multispot laser patterns into the far periphery by continuous prepositioning of the laser beam relative to eye movements. Owing to stable fixation, multispot treatment patterns may be applied with longer pulse durations (eg, 100 ms or longer). Hence, navigated panretinal pattern photocoagulation (nPRP) allows adherence to the EDTRS protocol.
Recently, conventional and navigated pattern PRP spots were compared for treatment of PDR. A study concluded that navigated PRP achieved more uniform laser burns compared to conventional pattern PRP. However, the clinical efficacy of navigated and conventional pattern laser has not been previously compared. This prospective, interventional, randomized trial compared the clinical efficacy of navigated pattern and conventional slit-lamp pattern PRP by assessing differences in the stability of visual acuity, regression or development of neovascularization, retreatments, and other surgical interventions.
Methods
Patients
This study was performed at the L V Prasad Eye Institute, Hyderabad, India and the King Khaled Eye Specialist Hospital (KKESH), Riyadh, Saudi Arabia. The study and data accumulation were carried out with approval from the Institutional Review Boards at each site. This study adhered to the tenets of the Declaration of Helsinki. Prior informed consent was obtained from the study patients, who subsequently underwent either navigated laser or conventional pattern laser treatment.
Patients were enrolled at both study sites. Inclusion criteria were age of 18 years or older with type 1 or 2 diabetes mellitus and high-risk PDR, defined as neovascularization at the optic disc (NVD); presence of NVD associated with vitreous or preretinal hemorrhage; and neovascularization elsewhere (NVE) with more than a half disc area associated with vitreous or preretinal hemorrhage. Patients with low-risk PDR features with special indications such as monocular status, patients with poor compliance, and pregnant patients were excluded. Other exclusion criteria were any history of prior panretinal laser treatment or vitrectomy in the study eye; history of anti-angiogenic injections within the previous 2 months; evidence of center-involved diabetic macular edema; intravitreal dexamethasone implant; media opacities such as significant cataract, corneal opacity, or vitreous hemorrhage obscuring fundus details; coagulation abnormalities; or use of anticoagulants other than aspirin.
All patients underwent a comprehensive ophthalmic evaluation including measurement of best-corrected visual acuity, slit-lamp biomicroscopy, intraocular pressure (IOP) measurement by applanation tonometry, and dilated funduscopy. Color fundus photographs and fluorescein angiography were performed at baseline prior to laser photocoagulation, as previously described.
Laser Procedure and Follow-up
Laser photocoagulation was performed using the NAVILAS (OD-OS GmbH, Berlin, Germany) laser system for patients randomized to navigated PRP or the PASCAL pattern scanning laser (Topcon Medical Laser Systems, Inc, Tokyo, Japan) for patients randomized to conventional single-spot or pattern PRP. Treatments were performed by the same vitreoretinal specialists at each site (J.C. and I.K.). Patients were consecutively enrolled and randomized into 4 groups: Group 1: navigated PRP with short pulse (20–30 ms) duration patterns (NAVILAS 30); Group 2: conventional PRP with short pulse (20–30 ms) duration patterns (PASCAL 30); Group 3: navigated pattern laser with long pulse (100–200 ms) duration (NAVILAS 100); Group 4: conventional single-spot laser with long pulse (100–200 ms) duration (PASCAL 100).
Laser parameters were as follows: power to achieve a grayish white burn, spot size of 300 μm for the navigated groups and 200 μm for the conventional groups; 1.5 burn width spacing for patterns and pulse duration according to the treatment group. All treatments with the NAVILAS laser were performed with a proprietary lens (OD-OS GmbH) with no spot magnification. Topical 0.5% proparacaine was instilled in the eye prior to placement of the lens. Therefore the spot was set at 300 μm, to achieve 300 μm burn on the retina to match the retinal burn size in the conventional groups. For all treatments with the PASCAL laser, a Mainster 165 PRP lens was used (Ocular Instruments Inc, Bellevue, Washington, USA) with 1.96× magnification. At KKESH only, patients graded their perception of pain using a visual analog pain scale (VAS). The VAS consisted of a 10-cm line, with 0 on one end representing no pain and 10 at the other end representing the worst pain ever experienced. The time for laser application was recorded to review the utility of the laser settings in each group.
All patients were evaluated from enrollment in January 2013 until their last visit at 6 months. Postoperatively, all participants underwent an ophthalmic examination including measurement of visual acuity, slit-lamp biomicroscopy, applanation tonometry, dilated funduscopy, and color fundus photography. A loss to follow-up was not recorded.
Statistical Analysis
All data were entered into a MS-Excel 2010 spreadsheet (Microsoft Corporation, Redmond, Washington, USA) and analyzed with Statistical Package R (Foundation for Statistical Computing, Vienna, Austria). Statistical significances were calculated with Student t test (visual acuity, treatment time, pain score), χ 2 test, and the relative risk (regression/recurrence rate of neovascularization, need for additional treatment). A P value less than .05 was considered statistically significant.
Results
Patients and Laser Procedure
The study sample was composed of 74 eyes (52 eyes from L V Prasad Eye Institute and 22 eyes from KKESH) of 47 patients with high-risk PDR. There were 21 eyes in Group 1, 22 eyes in Group 2, 17 eyes in Group 3, and 14 eyes in Group 4. Table 1 presents the mean age of the patients, baseline ocular characteristics, and number of laser applications for all groups. At the end of the procedure all visible retinal areas were filled with photocoagulation burns. The laser power to produce white retinal burns was similar among all groups (200–400 mW), as was density of laser applications. All treatments were uneventful and no adverse events such as bleeding or vision loss occurred.
| Pulse | Pattern | Number of Eyes | Age | Mean VA (SD) (logMAR) | Mean Follow-up (SD) (mo) | NVD | NVE | VH | Mean Number of Spots (SD) |
|---|---|---|---|---|---|---|---|---|---|
| 30 ms | Navigated pattern | 21 | 51 ± 9 | 0.37 ± 0.32 | 6 ± 3 | 6 | 18 | 2 | 1810 ± 369 |
| 30 ms | Conventional pattern | 22 | 55 ± 7 | 0.47 ± 0.31 | 5 ± 4 | 7 | 19 | 5 | 2334 ± 656 |
| 100 ms | Navigated pattern | 17 | 53 ± 10 | 0.52 ± 0.52 | 6 ± 2 | 11 | 11 | 3 | 1120 ± 446 |
| 100 ms | Conventional single-spot | 14 | 52 ± 8 | 0.62 ± 0.52 | 5 ± 3 | 7 | 9 | 3 | 1433 ± 513 |
Visual Acuity
There was no significant change in visual acuity in any of the groups ( Table 2 ). There was no change in visual acuity in the navigated short pulse group. There was minor (but not statistically significant) loss of visual acuity in the conventional short pulse group.
| Pulse | Pattern | Baseline VA (SD) (logMAR) | Follow up VA (SD) (mo) | P |
|---|---|---|---|---|
| 30 ms | Navigated pattern | 0.37 ± 0.32 | 0.37 ± 0.37 | .35 |
| 30 ms | Conventional pattern | 0.47 ± 0.31 | 0.53 ± 0.43 | .47 |
| 100 ms | Navigated pattern | 0.52 ± 0.52 | 0.47 ± 0.36 | .52 |
| 100 ms | Conventional single spot | 0.62 ± 0.52 | 0.53 ± 0.44 | .62 |
Regression/Development of Neovascularization
Both NVD and NVE were grouped together and analyzed as “neovascularization” as they both represent the same process in different locations. We have used clinical and fluorescein angiographic criteria to diagnose the presence/regression of neovascularization. There was no statistically significant change in the development or resolution of neovascularization in all groups ( Table 3 ). There was no new development of neovascularization in Groups 3 and 4 (long pulse) out to 6 months postoperatively. Nine percent of eyes in Group 1 (navigated short pulse) and 5% of eyes in Group 2 (conventional short pulse) developed new neovascularization. The resolution of neovascularization was highest in the 30 ms conventional group (23% of eyes with neovascularization resolved) and lowest in the 30 ms navigated pattern group (5% resolution rate). Neovascularization resolved in 3 of 17 eyes (18%) in the navigated long pulse and 2 of 14 eyes (14%) in conventional long pulse group. There was no statistical difference in the development of neovascularization between the short-pulse-duration groups and long-pulse-duration groups.
Need for Additional Treatment
The need for additional treatment included presence/development of vitreous hemorrhage or persistent neovascularization. Table 4 presents the proportion of eyes in each group that required additional therapeutic procedures. One eye in the navigated short pulse group and 1 eye in the conventional short pulse group required vitreoretinal surgery owing to nonclearing vitreous hemorrhage that spared the visual axis. None of the eyes in the long pulse groups required additional surgery. These events were not statistically significantly different between the short-pulse-duration (Groups 1 and 2) and Long-Pulse-Duration (Groups 3 and 4) groups ( P = .98). Short-pulse-duration groups required 22 procedures and long-pulse-duration groups required 12 procedures. This difference was statistically significant ( P < .05). A trend toward worse outcome (additional procedures) using short-pulse-duration treatments is expressed by slightly increased relative risk of 1.3 compared to the long-pulse-duration treatments ( Table 4 ).
