Purpose
To evaluate the efficacy of the pattern scan laser (PASCAL) in treating newly diagnosed high-risk proliferative diabetic retinopathy (PDR).
Design
Retrospective comparative case series.
Methods
setting: Institutional. study population: Eighty-two consecutive eyes of the same number of patients with newly diagnosed high-risk PDR treated with panretinal photocoagulation (PRP) using either argon green laser (41 eyes treated before February 2007) or PASCAL (41 eyes treated February 2007 or thereafter), then followed for at least 6 months. procedure: Retrospective chart review with attention to main outcome measures, age, sex, race, follow-up interval, insulin dependence, hemoglobin A1c, and total number of lasers spots. main outcome measures: Persistence or recurrence of neovascularization, incidence of vitreous hemorrhage (VH), neovascularization of the iris (NVI), neovascular glaucoma (NVG), and need for vitrectomy.
Results
Patients treated with the PASCAL and argon laser received a similar number of spots (1438 vs 1386; P = .59). Patients treated with the PASCAL were more likely to experience persistence or recurrence of neovascularization within 6 months of initial treatment (73% vs 34%; P < .0008). The study was not adequately powered to detect a significant difference in incidence of vitreous hemorrhage, NVI, NVG, or need for vitrectomy.
Conclusions
When using traditional laser settings, PRP performed with the PASCAL is less effective than that performed with traditional argon laser in effecting lasting regression of retinal neovascularization in the setting of previously untreated high-risk PDR. Physicians may need to change treatment parameters when using PASCAL pattern laser therapy for high-risk PDR.
In 1976, the Diabetic Retinopathy Study (DRS) reported that panretinal photocoagulation (PRP) for proliferative diabetic retinopathy (PDR) with high-risk characteristics decreased the risk of severe vision loss by over 50% out to 4 years of follow-up. Thereafter, PRP became the gold standard for treatment of high-risk PDR. Clinicians now perform PRP using various wavelengths including argon green (514 nm), krypton red (647 nm), diode (810 nm), and tunable dye (560-640 nm) lasers. Traditionally laser burns have been placed one by one in a grid pattern outside the vascular arcades, with spot size ranging from 100 to 500 μm and pulse durations from 100 to 200 ms. Based on the DRS, at least 1500 PRP burns are delivered using this technique. Because placing so many laser spots often leads to patient discomfort and fatigue, PRP is usually performed over several sessions.
Blumenkranz and associates have developed a new frequency-doubled 532-nm-wavelength Nd:YAG laser capable of delivering arrays of up to 56 spots over the course of less than 0.6 seconds following a single foot pedal depression. Named the PASCAL (PAttern SCAn Laser; Topcon Medical Laser Systems, Santa Clara, California, USA), the commercially available version of the 532-nm Nd:YAG diode laser is marketed as a less painful and safer alternative to the argon laser for both PRP and macular photocoagulation. The pattern scan laser’s capability to deliver nearly simultaneously a grid of short-duration laser pulses, each 1 magnitude shorter in duration than the argon laser pulse, also results in a quicker PRP procedure. As pulse durations are decreased below 50 ms, the mechanism of cellular injury transitions from thermal energy at higher pulse durations to mechanical rupture because of transient vapor formed adjacent to melanosomes. Without thermal energy, laser-induced damage is limited to retinal pigment epithelium and photoreceptors, sparing the choroid and inner retina. Since thermal diffusion to the sensory neuron–rich choroid seen with argon laser but not PASCAL burns causes the perception of pain, patients treated with the PASCAL often lack the discomfort once associated with PRP. In the sense that inner retina and choroid are spared, the PASCAL laser is safer. However, as pulse duration is decreased below 50 ms, the ratio of power required for rupture of the Bruch membrane to the power resulting in a sub-therapeutic burn grows larger as the difference between the 2 powers grows smaller. Thus, the clinician experiences a smaller safety margin when titrating the power of the PASCAL.
The PASCAL is now being substituted for the traditional argon laser for macular photocoagulation (MP) and PRP in many clinics. However, we are not aware of any study that has compared clinical outcomes for the 2 lasers when used to treat high-risk PDR. This retrospective comparative study evaluates whether PRP performed via the PASCAL is as efficacious as traditional argon laser PRP in the setting of newly diagnosed high-risk PDR.
Methods
After institutional review board approval, a retrospective review was performed of consecutive patients from February 2007 to November 2007 who met the following inclusion criteria: 1) age greater than 18 years; 2) newly diagnosed high-risk PDR; 3) no history of or clinical evidence of prior PRP; 4) if presence of vitreous hemorrhage, then vision greater than 20/200; 5) follow-up of at least 6 months; and 6) subsequent PRP treatment for high-risk PDR using the PASCAL pattern laser. High-risk PDR was defined as neovascularization of the disc (NVD) greater than one-third disc area (DA), NVD associated with vitreous hemorrhage or preretinal hemorrhage (PRH), or neovascularization elsewhere (NVE) at least one-half DA in size and associated with vitreous hemorrhage or PRH. A total of 41 consecutive eyes were identified. We then identified an equal number of consecutive eyes using the same inclusion criteria, except that PRP was performed using a traditional argon green laser with either direct or indirect ophthalmoscopy prior to acquisition of the PASCAL (January 2007 or earlier). Though after January 2007 the PASCAL replaced the argon laser as the dominant modality for PRP at our institution, argon laser was occasionally employed in certain circumstances (for example, extensive vitreous hemorrhage).
All PRP procedures were performed in a darkened room, approximately 30 minutes after the study eye was pharmacologically dilated with 1% tropicamide and 2.5% phenylephrine. All eyes were anesthetized with topical proparacaine drops. Some patients opted to receive additional retrobulbar anesthesia with 2% lidocaine solution.
For the argon group, 1 of 2 identical Coherent, Inc (Santa Clara, California, USA) Novus Omni argon lasers was used to deliver 514-nm (green) pulses approximately 1 burn width apart. Patients were treated with either the indirect headset with a handheld lens or the slit-lamp microscope with a contact lens with spot-size magnification factor of 2×, to focus the laser. The following settings were used for lasers performed with a contact lens: pulse duration 200 ms; spot size 200 to 300 μm; power 200 mW, increased by 10 to 20 mW until a gray/white lesion was attained. The majority of patients opted to divide the treatment between 2 or 3 sessions, though 37% completed the entire PRP in 1 session.
PASCAL PRP was performed on 1 of 2 identical lasers, again using a contact lens with an approximate 2× spot-size magnification. Settings were set as follows: 200 μm spot size, 20 ms pulse duration, power increased from 200 mW until a gray-white lesion was attained. Burns were placed 1 burn width apart. Whether laser burns were delivered as a small or larger array was determined by operator preference. Forty-four percent of patients completed the entire treatment in 1 session, with the remainder requiring 1 or 2 additional sessions.
Failure of neovascularization to regress following treatment with at least 1400 spots or recurrence of neovascularization following initial regression was the primary outcome measure. “Failure to regress” or “persistence” was defined as failure to show significant regression of neovascularization at 3 months or more from the initial PRP treatment and at least 1 month after the last session of the PRP laser had been completed. “Recurrence” of neovascularization was defined as neovascularization occurring after initial regression at any time during the follow-up period of 6 or more months. “Treatment failures” were patients who had shown either failure to regress (persistence) or recurrence of neovascularization over the time of follow-up. Conversely, all patients in the successfully treated group showed complete or near-complete regression of neovascularization at 3 months from the initial PRP application and showed no recurrence of the neovascularization during the follow-up period.
Secondary outcome measures included incidence of post-laser vitreous hemorrhage, neovascularization of the iris (NVI), neovascular glaucoma (NVG), and requirement for pars plana vitrectomy (PPV).
All patients who had recurrence or persistence of neovascularization received salvage treatment as was deemed appropriate by the treating physician. This included additional laser, intravitreal bevacizumab, a combination of both, or vitrectomy surgery.
Statistical Analysis
Data are expressed as mean values (standard deviation) or number of patients affected (percent of patients affected). Outcome measures for PASCAL-treated vs argon laser–treated groups were compared using the Fisher’s exact t-test for nonparametric data, using an alpha error rate of 0.05. Continuous or nominal variables such as age, HbA1c, number of laser spots, and days of follow-up were compared using the Student t test under the assumption of a normal distribution.
Results
Eighty-two patients were included in the study, 41 in the traditional argon laser group and 41 in the PASCAL pattern laser group. At baseline, the 2 groups did not differ significantly ( P > .05) with respect to age, total number of laser spots placed, most recent HbA1c, sex, or insulin requirements ( Table 1 ). The argon laser group included significantly more African-American patients ( P < .01).
| PASCAL | Argon Laser | P Value | |
|---|---|---|---|
| Age, mean ± SD (years) | 57.9 ± (2.5) | 55.8 ± (1.9) | .50 |
| Sex, n (%) | |||
| Female | 16 (46) | 18 (45) | >.99 |
| Male | 19 (54) | 22 (55) | |
| Race, n (%) | |||
| AA | 9 (26) | 23 (58) | >.99 |
| Non-AA | 26 (74) | 17 (42) | |
| HbA1c, mean ± SD (%) | 8.1 ± (0.40) | 8.2 ± (0.29) | .79 |
| Insulin dependence, n (%) | |||
| NIDDM | 7 (20) | 13 (33) | .30 |
| IDDM | 28 (80) | 27 (67) |
The mean number of laser spots delivered did not differ depending on whether the PASCAL or argon laser was used (1438 vs 1386; P = .59). However, patients treated with the argon laser were followed on average for a longer duration (410 days) compared to patients treated with the PASCAL (313 days) ( P = .0003).
Seventy-three percent (30 of 41) of eyes that received PRP via PASCAL experienced treatment failure as evidenced by persistence or recurrence of neovascularization within 6 months of initial treatment, compared to 34% (14 of 41) of those eyes treated with traditional argon PRP ( P = .0008; Figure 1 , Table 2 ). Eight out of 41 eyes (20%) treated using the PASCAL failed to exhibit regression of neovascularization following treatment with at least 1400 spots, compared to only 1 out of 41 eyes (2%) treated with argon laser ( P = .01; Table 2 ). Twenty-two of the 33 eyes (54%) that initially responded to the PASCAL treatment exhibited recurrence of neovascularization following PASCAL treatment, compared to 13 of 40 (33%) treated with the argon laser ( P = .008; Table 2 ).
