Graefe's Archive
Graefe's Arch Clin Exp Ophthalmol (1990)228:226-231
for Clinical and
Experimental
Ophthalmology © Springer-Verlag 1990
The effect of short versus long exposure times of argon laser panretinal photocoagulation on proliferative diabetic retinopathy Edward C. Wade and George W. Blankenship Department of Ophthalmology, Bascom Palmer Eye Institute, University of Miami School of Medicine, Miami, Fla, USA
Abstract. We performed a randomized clinical trial comparing short-duration (0.1 s) with long-duration (0.5 s) bluegreen argon laser burns to deliver panretinal photocoagulation (PRP) in eyes suffering from proliferative diabetic retinopathy with high risk characteristics. We studied 19 eyes in the 0.1-s group and 24 eyes in the 0.5-s group for 6 months. Two or more lines of acuity were lost by 20% of the 0.1-s PRP eyes, but by only 8% of the 0.5-s PRP eyes; New or increased vitreous hemorrhages occurred in 30% of the 0.1-s PRP eyes, but in only 16% of the 0.5-s PRP eyes; New or increased traction retinal detachments did not occur in the 0.l-s PRP eyes, but occurred in 16% of the 0.5-s PRP eyes. There was complete disc neovascular regression in 85% of the 0.1-s PRP eyes and 81% of the 0.5-s PRP eyes. These trends were not statistically significant.
Introduction The Diabetic Retinopathy Study (DRS) [3-6] determined that panretinal photocoagulation (PRP) using blue-green argon or xenon light wave lengths reduces the chance of severe visual loss from proliferative diabetic retinopathy. The mechanism by which PRP induces neovascular regression and prevents further neovascular development, which reduces the risk of severe visual loss, is not known. Laser burns made by different exposure durations produce different chorioretinal scars [15] which may alter the effectiveness of PRP. The treatment effect with longer duration exposure burns may be better, the same, or not as good as the effect obtained with shorter duration burns. This article describes the results of a randomized, prospective, clinical trial evaluating the efficacy and side effects of PRP using short (0.1 s) vs long (0.5 s) exposure time with the blue-green argon laser. Materials and methods Eyes of informed and consenting patients with three or four of the possible four diabetic retinopathy risk factors for severe visual loss as determined by the DRS [5] were Offprint requests to: G.W. Blankenship, Department of Ophthalmology, Pennsylvania State College of Medicine, P.O. Box 850, Hershey, PA 17033, USA
treated with blue-green argon laser PRP. Five hundred micron spots of either short (0.1 s) or long (0.5 s) duration were used with sufficient energy to obtain a moderate blanching of the neurosensory retina overlying the pigment epithelial burn. The burn duration of each case was randomly selected. To be eligible, the patient had to have a diagnosis of diabetes mellitus, be able to return for postlaser examinations at 1 week, i month, and 6 months, and be willing to participate in a random selection of either 0.l-s or 0.5-s burn exposure time. Ocular eligibility criteria of the involved eye required best corrected visual acuity of 6/30 or better, media clarity sufficient for PRP in a single session and three or four diabetic retinopathy risk factors. Eyes with prior photocoagulation, or substantial lens or vitreous opacities sufficient to prevent PRP, were ineligible. The pretreatment examination consisted of obtaining general information regarding the patient's age, sex, race, duration of diabetes, and means of blood glucose control. The eye examination consisted of obtaining a best-corrected visual acuity with a projected Snellen chart, slit lamp examination, applanation tonometry, fundus examination with indirect ophthalmoscopy, and a Hruby lens or 90-D condensing lens. Pretreatment 60 ° stereo color photographs were taken. Macular thickening was present when there was increased width of the slit lamp beam within I disc diameter of the center of the macula. Neovascularization of the disc (NVD) was graded using DRS standard photograph 10A showing one-fourth to one-third disc area surface neovascularization for comparison [3]. Neovascularization elsewhere (NVE) was graded as in the DRS as less than 0.5 disc diameters or more extensive. After the patient had been informed and had consented to participate, a coin was flipped which determined whether the eye was to receive short (0.l-s)- or long (0.5-s)-duration exposure times with the blue-green argon laser. Recruitment and randomization continued until there were 25 treated eyes in the 0.1-s group, with the last two cases in the 0.5-s group being assigned rather than randomized to make an equal number of eyes in each group. The PRP was performed in a single treatment session using retrobulbar anesthesia through a widely dilated pupil. Blue-green argon laser was used with a 500-gm spot size at 0.1- or 0.5-s exposure time using sufficient energy to obtain moderate blanching of the retinal pigment epithelium. A panscopic fundus contact lens was used, and the
227 laser burns were placed around the arcades and 2 disc diameters temporal to the center of the macula extending peripherally as far as possible. The burns were placed approximately one-half burn width apart. The patients randomized to P R P with 0.1-s exposure time had between 650 and 1000 spots (mean 767) produced with power settings from 0.7 to 1.5 W (mean 1.05 W). The 0.5-s P R P group had between 500 and 900 spots (mean 710) produced with power settings from 0.3 to 0.6 W (mean 0.4; Figs. 1, 2, 3). Post-treatment medications were not used for either group. Follow-up examinations identical to the pretreatment examinations were performed at I week, 1 month, and 6 months after treatment, and as indicated by each individual case. Results
Fig. 1. Blue-green argon laser burns (500 pm) produced with 0.l-s (upper burn) and 0.5-s (lower burn) durations
A total of 41 patients participated in the study with 50 eyes receiving treatment. Twenty-five eyes randomized to short (0.l-s) exposure time, and 23 eyes were randomized and 2 were assigned to long (0.5-s) exposure time. Six-month follow-up was available on 20 (80%) of the 25 eyes in the 0.1-s group, and 24 (96%) o f the 25 eyes in the 0.5-s group. Of the five patients (six eyes) unavailable for follow-up, one patient died of a massive gastrointestinal hemorrhage 1 month after PRP, and four patients could not be located. We evaluated the data on 44 eyes with 6-month follow-up.
Pretreatment evaluation The 19 patients randomized to receive 0.1-s P R P consisted of nine (48%) men and ten (52%) women whose ages ranged from 18 to 82 years (mean 48 years). They had Table 1. Numbers of eyes and visual acuities
Fig. 2. Panretinal photocoagulation using 0.1-s duration, 500 gm blue-green argon laser wave lengths
6/6-6/7.5
6/9-6/15
6/18-6/30
_+4
+3-+2
+1---1
--2--3
_>-4
No. (%)
No. (%)
No. (%)
No. (%)
No. (%)
1 Month posttreatment 0.1 s 1 (5) 1 (5) 0.5s 0 (0) 3 (12)
14 (70) 15 (64)
4 5
(20) (20)
0 1
(0) (4)
6 Month posttreatment 0.1 s 1 (5) 2 (10) 0.5 s 3 (12) 5 (20)
13 (65) 14 (60)
2 1
(10) (4)
2 1
(10) (4)
228 Table 3. Change in neovascularization of the disc Pretreatment at 0.1 s None
Pretreatment at 0.5 s >_DRS10A a
None
DRS 10A"
11 1 0
5 1 0
2 0 0
11 4 t
10 2 0
6 0 0
2 0 0
13 3 0
1/2 DA 0 0
8 3 2
9 0 0
0 0 0
10 5 0
I Month posttreatment None < 1/2 DA > I/2 DA
7 0 0
a Disc area
k n o w n of their diabetes for 8-38 years (mean 20 years), and at the time of entering the study, 16 (85%) were receiving insulin a n d 3 (15%) were using oral hypoglycemics. There were 12 (60%) right eyes a n d 8 (40%) left eyes. The 24 patients randomized to receive 0.5-s P R P consisted of 12 (50%) m e n a n d 12 (50%) w o m e n whose ages ranged from 19 to 71 years (mean 49 years). They had k n o w n of their diabetes for 2-40 years (mean 18 years); 21 (88%) were receiving insulin and 3 (12%) were using oral hypoglycemics. There were 9 (35%) right eyes and 15 (65%) left eyes. Pretreatment best-corrected visual acuities for both the 0.1-s a n d 0.5-s P R P eyes are compared with those obtained at i and 6 months after treatment in Tables 1 a n d 2. The cases randomized to 0.l-s P R P had slightly better pretreatment visual acuities. Sixteen eyes (80%) in the 0.l-s P R P group had 6/15 or better pretreatment visual acuity, whereas in the 0.5-s P R P group, only 12 eyes (50%) had 6/15 or better. S u b n o r m a l visual acuity was caused by m i n o r cateracts, vitreous hemorrhages, and macular disease. The pretreatment anterior segment examinations found m i n o r iris neovascularization a r o u n d the pupillary margins in none of the eyes in the 0.l-s P R P group, b u t in one eye in the 0.5-s P R P group. All eyes had intraocular pressures of less t h a n 30. M i n o r vitreous cavity and preretinal hemorrhages were present in 11 (55%) of the 0.l-s P R P and 12 (50%) of the 0.5-s P R P eyes. Macular thickening was present in m a n y of the eyes prior to PRP. F o u r (20%)
of the 0.1-s P R P eyes and eight (34%) of the 0.5-s eyes had some degree of macular thickening. One eye in each group had an epimacular membrane. Extramacular traction detachments were present in two (8%) of the 0A-s eyes a n d in six (25%) of the 0.5-s eyes. N o n e of the eyes in either group had macular detachments. N V D was usually present before PRP. Twelve of the 20 (60%) 0.1-s and 16 of the 24 (67%) 0.5-s P R P eyes had N V D greater or equal to the D R S standard photograph No. 10A (see Figure 1). A n additional two (10%) of the 0.l-s and two (8%) of the 0.5-s P R P eves had less extensive N V D (Table 3). N V E equal to or greater than one-half disc area was present in 13 of 20 (65%) eyes in the 0.1-s and 15 of 24 (63%) eyes in the 0.5-s group (Table 4). Of the eyes r a n d o m l y assigned to 0.1-s PRP, 16 (80%) had 3 retinopathy risk factors, and the remaining 4 (20%) had 4 risk factors. The 0.5-s group had 19 (79%) with 3 risk factors and the remaining 5 (21%) had 4 risk factors [5].
Early postlaser evaluation After panretinal laser photocoagulation there were minor inflammatory changes observed at the day 7 follow-up examination, b u t the prevalence a n d extent of these early side effects in the two groups were similar. One eye in the 0.5-s group, but none in the 0.l-s group, had moderate shallowing of the anterior chamber. None of the eyes in either group had intraocular pressures greater than 30 mmHg. Shallow peripheral choroidal detachments occurred in 1 of 20 (5%) eyes in the 0.l-s group and 4 of 24 (17%) eyes in the 0.5-s group. One eye in each group developed a peripheral exudative retinal detachment without macular involvement that resolved by the visit 1 month. Macular thickening was noted in 9 of 20 (45%) eyes in the 0.1-s group and 9 of 24 (38%) eyes in the 0.5-s group i week after treatment. I n the 0.1-s eyes, all four eyes that had macular thickening prior to P R P had an increase m macular thickening I week after PRP. I n the 0.5-s eyes four of eight eyes with macular thickening prior to P R P developed an increase in macular thickening I week after PRP.
Postlaser treatment evaluation at 1 month The inflammatory reactions present during the first week following PRP had resolved by the post-treatment examinations at 1 month. The best-corrected visual acuities 1 m o n t h after PRP are shown in Table 1. Two (10%) eyes in the
229 0.1-s group had visual acuities of 6/60 or worse. One was due to a preretinal hemorrhage, and the other eye had an opacified posterior lens capsule that improved to 6/7.5 after Nd Y A G capsulotomy. Three 0 2 % ) eyes in the 0.5-s group had visual acuities of 6/60 or worse. One eye developed a combined traction and rhegmatogenous retinal detachment that was subsequently successfully repaired, one eye had increased macular thickening, and the other eye had a macular hole. Table 2 shows the changes of visual acuity from the pretreatment level with the majority of eyes in both groups having changed one line or less. Substantial clearing of pretreatment vitreous hemorrhage was common, and new bleeding was uncommon after PRP. New vitreous or preretinal hemorrhage was present in four (20%) eyes in the 0.1-s PRP group and three (13%) eyes in the 0.5-s PRP group. Most of the increased macular thickening at the 1 week follow-up examination had resolved by I month. Of the nine eyes in the 0.l-s group, only one eye had persistence of the increased macular thickening. Of the nine eyes in the 0.5-s group with increased macular thickening at 1 week, two had persistence of the thickening. The two pretreatment extramacular traction detachments in the 0.1-s group remained the same, but in the 0.5-s group, one of the six (18%) eyes with a pretreatment extramacular traction detachment developed a combined rhegmatogenous and traction retinal detachment as mentioned above. No new traction detachments developed in the 0.1-s group, but 3 of the 18 0 6 % ) eyes in the 0.5-s group without pretreatment traction retinal detachments developed extramacular traction detachments at 1 month. This difference was not statistically significant and would require a sample size of 50 subjects in each group to have an 80% chance of detecting significance at a P = 0.05 level. Disc neovascularization had substantially regressed in both groups (Table 3). Of the eyes with pretreatment NVD equal to or greater than DRS photo 10A, l l of 12 (92%) of the 0.l-s group had no NVD and I (8%) had partial regression, and Ii of 16 (70%) of the 0.5-s group had no NVD, 4 (25%) had partial regression, and the remaining eye (5%) had presistent NVD equal to or greater than DRS photo 10A. One eye in the 0.5-s group that did not have pretreatment NVD developed NVD. The change in NVE is shown in Table 4 with regression of NVE being almost identical for both treatment groups. Postlaser treatment evaluation at 6 months
None of the eyes in either group received additional laser treatment prior to the 6-month follow-up exam, but a pars plana vitrectomy had been performed on one eye in the 0.5-s group that developed a combined rhegmatogenous and traction retinal detachment I month following PRP with successful retinal reattachment. Most of the eyes maintained good visual function with substantial clearing of vitreous hemorrhage and regression of disc and retinal neovascularization, indicating a substantially improved prognosis for maintaining good visual function. The best-corrected visual acuities are shown in Table 1. In the 0.l-s group, 80% had 6/15 or better acuities compared with 68% of the 0.5-s eyes. This difference is not statistically significant. The changes in visual acuities are shown in Table 2. Approximately 60% of eyes in both groups stayed within
one line of their pretreatment visual acuities. Improved acuities were more common in the 0.5-s group, and decreased acuities were more common in the 0.l-s group. In the 0.l-s group, three (15%) eyes had improved vision: two improvements were due to vitreous hemorrhage clearing; one was due to a Nd Y A G capsulotomy of an opacified posterior capsule. Eight eyes (32%) in the 0.5-s group had improved six due to vitreous hemorrhage clearing, and two due to decreased macular thickening. This difference was not statistically significant and would require 82 eyes in each group to have an 80% chance of detecting significance at a P = 0.05 level. A decrease in vision was more common in the 0.1-s group. Four (20%) eyes in the 0.1-s group lost two or more lines: three losses were due to vitreous hemorrhage, and one eye had a central retinal artery occlusion. In the 0.5-s group, only two (8%) eyes lost two or more lines: one was the eye with the retinal detachment which had increased cateract after surgery, and the other also had an increased cataract. Iris neovascularization regressed in the one eye in which it was present prior to PRP in the 0.5-s group. No iris neovascularization developed in either group throughout the study. All eyes in both groups maintained intraocular pressures below 30 mmHg throughout the study. There was no significant change in lens opacities throughout the study in either group except for one eye in the 0.1-s group that developed an opacity of the posterior capsule requiring Nd YAG capsulotomy and the two eyes in the 0.5-s group. New or increased preretinal or vitreous hemorrhages were uncommon in both groups, although they were less common in the 0.5-s group. Six of the 20 eyes (30%) in the 0.1-s group had bleeding within 6 months after PRP. All of the hemorrhages cleared without requiring pars plana vitrectomy. Four of the 24 eyes (16%) in the 0.5-s group had vitreous or preretinal hemorrhage, none of which required vitrectomy. This difference was not statistically significant and would require 134 eyes in each group to have an 80% chance of detecting significance at a P = 0.05 level. Macular thickening was present 6 months after PRP in only two eyes in the 0.1-s group, one eye had no change in the pretreatment macular thickening, and one eye having no macular thickening prior to PRP developed mild macular thickening. One of the eyes in the 0.5-s group had less macular thickening at the 6-month exam than before treatment. None of the eyes in either group developed new traction retinal detachments between the 1-month and 6-month examinations. The two extramacular traction retinal detachments present prior to PRP in the 0.1-s group did not progress. The combined traction and rhegmatogenous retinal detachment in the 0.5-s group that developed 1 month following PRP had been successfully repaired, and the other eight extramacular traction detachments remained unchanged. This difference was not statistically significant. There was substantial NVD regression in both groups, and none of the eyes in either group had NVD equal to or greater than DRS photo 10A (Table 3). Of the eyes with pretreatment NVD equal to or greater than DRS photo 10A, 10 of 12 (85%) of the 0.l-s group had no NVD, and 2 (15 %) had partial regression; 13 of 16 (81%) of the 0.5-s group had no NVD, and 3 (19%) had partial regression. This difference was not statistically significant. There was also substantial NVE regression in both groups. Complete
230 NVE regression was accomplished in 8 of the 13 (60%) 0.1-s eyes, and in 10 of the 15 (67%) 0.5-s eyes. Discussion
The DRS findings [3-6) confirmed the benefits of PRP treatment in reducing the incidence of severe visual loss and regressing neovascularization in the majority of eyes with proliferative diabetic retinopathy. The DRS protocol PRP treatment used 800-1600 blue-green argon burns of 500-gm spot size and 0.1-s duration. The mechanism by which PRP causes neovascular regression is not known. Panretinal photocoagulation has been shown to increase preretinal oxygen tension possibly by: (a) thinning the RPE and outer retinal layers and thereby increasing choroidal oxygen diffusion to the inner retina; and (b) destroying the outer retina and RPE that account for most of the retinal oxygen consumption [13, 14]. The increase in available oxygen to the inner retina may reduce the liberation of an angiogenic factor. Previous histological studies on human eyes have confirmed that 0.5-s, blue-green argon burns produce larger scars and thinning of the retina than 0.1-s burns [15]. Therefore, there is a theoretical, but unproven, consideration that longer duration burns may increase preretinal oxygen tension above the levels seen with shorter burns, thereby reducing the stimulus for angiogenic factor more effectively. The ophthalmoscopic and photographic appearance of the 0.1-s and 0.5-s burns with our treatment were identical. This was accomplished by markedly reducing the energy used with the longer duration burns. This identical appearance and apparent size suggests, but certainly does not prove, that the burns were of equal intensity and involved the same volume of retina. Randomization to treatment groups upon entry into the study resulted in both groups being comparable with respect to age, sex, duration of disease, use of insulin, incidence of iris neovascularization, glaucoma, cateracts, vitreous hemorrhages, NVD, NVE, and number of retinopathy risk factors. The 0.l-s group had slightly better pretreatment visual acuities, less macular thickening, and fewer extramacular traction retinal detachments than the 0.5-s group. The number of burns was also comparable. The blue-green argon wave lengths were used in our study to make the findings more comparable to the DRS and other more recent studies. Eliminating the blue wave length component of argon laser may reduce intraretinal energy absorption and subsequent scarring and traction, but the results of PRP treatment of diabetic retinopathy with high-risk characteristics using only green argon wave lengths has not been reported. We analyzed several parameters following PRP. Most of the eyes (60%) in both groups maintained visual acuities within one line of the pretreatment level. There was a trend, however, for more eyes in the 0.5-s group (32% vs 15%) to have improved vision at the 6-month exam. Most of these eyes had improved acuities due to clearing of vitreous hemorrhages. Although the prevalence of vitreous hemorrhage prior to PRP was similar in both groups, it was more common for vision to be reduced by vitreous hemorrhage prior to PRP in the 0.5-s group, leaving more room for improvement over the following 6 months. Thus, apparent greater frequency of improved vision in the 0.5-s group may be due to their poorer pretreatment acuities.
A decrease in visual acuity of two or more lines 6 months pos.t-PRP was more common in the 0.l-s than in the 0.5-s group (20% vs 8%). In the 0.1-s group, this was due to vitreous hemorrhages in three eyes and a central retinal artery occlusion in one eye. In the 0.5-s group, one eye developed a combined traction and rhegmatogenous retinal detachment which was successfully repaired but developed a dense cataract, and one eye had a progressive cataract. McDonald and Schatz [10] treated eyes with 0.05-s duration burns and had a 28% prevalence of visual loss in patients followed for 3-12 months, which is similar to what we found in our 0.1-s group, but three times greater than results from our 0.5-s group. Most of the patients in their series lost vision from macular thickening and vitreous hemorrhages. In the DRS [4], 15% of 0.1-s argontreated eyes had a similar visual loss of tow lines or more 4 months after treatment. Two or more lines of vision were lost in 24% of the eyes in a single vs multiple treatment clinical trial [7], 17% of the eyes in an argon vs krypton clinical trial [1], 24% of the eyes in the central PRP, and 8% of the eyes in the peripheral PRP clinical trial [2]. All of these trials used 0.1-s burns except for the krypton treated eyes which were treated with 0.2-s burns. New or increased preretinal or vitreous hemorrhages were more common in the 0.l-s than in the 0.5-s group (30% vs 16%). In both groups, NVD and NVE regressed equally; however, the neovascularization that persisted in the 0.1-s eyes was more likely to bleed. New vitreous hemorrhages occurred in I 4 % - 2 8 % of eyes in previous series [1, 2, 71. Both treatment groups had better NVD and NVE regression than those in previous reports. Complete regression of pretreatment N V D equal to or greater than DRS standard photo 10A occurred in 85% of the 0.1-s eyes and 81% of the 0.5-s eyes. In the DRS [4], similar complete regression of extensive disc neovascularization was observed in only 29.8% of 188 eyes 12 months after treatment. Little's [9] series found 50% of eyes with similar NVD had complete regression. Complete regression of similar NVD was observed in 49% of the eyes in the single vs multiple session trial [7], 56% of eyes in the argon vs krypton trial [1], and 43% of the eyes in the central vs peripheral trial
[2]. Macular thickening was present in four (20%) eyes in the 0.l-s and eight (34%) eyes in the 0.5-s group before treatment. One week after PRP, macular thickening was present in nine eyes in each group. All four of the 0.1-s eyes with pretreatment macular thickening had increased thickening, and four of eight 0.5-s eyes with pretreatment thickening had increased thickening 1 week after PRP. This agrees with previous observations that eyes with macular thickening prior to PRP are more likely to develop an increase in the thickening following PRP [8, 10-12]; At the 1 month exam, macular thickening had improved in most eyes. Only one 0.1-s eye and two 0.5-s eyes had macular thickening. By the 6 month exam, two (10%) 0.1-s eyes and one (4%) 0.5-s eye had macular thickening:. This is in contrast to the report by McDonald and Schatz [14] who found persistent macular edema for 8-32 months following PRP in 47 (27%) of 175 eyes. Only 16 (8%) of 175 eyes lost vision due to persistent macular edema. Their prevalence may be higher because they performed fluorescein angiography on follow-up examinations which may increase the sensitivity of diagnosing mild macular edema.
231 There were no new traction retinal detachment or p r o gression o f pretreatment traction retinal detachments in the 0.l-s eyes. One o f the six 0.5-s eyes with a pretreatment extramacular traction retinal detachment developed a combined traction and rhegmatogenous retinal detachment involving the m a c u l a 1 m o n t h after PRP. Three 0.5-s eyes developed new traction retinal detachments; none o f these involved the macula. The findings o f this prospective, randomized clinical trial comparing 0.1-s with 0.5-s blue-green argon laser P R P in eyes suffering from proliferative diabetic retinopathy with high-risk characteristics indicate that b o t h treatments are effective in achieving regression o f disc and retinal neovascularization and in maintaining stable vision in the maj o r i t y o f eyes. The slightly lower prevalence o f new vitreous or preretinal hemorrhages as well as the lower prevalence o f loss o f two or m o r e lines o f visual acuity in the 0.5-s eyes indicates that longer duration burns m a y be m o r e effective in the treatment o f proliferative diabetic retinopathy; however, this was only a trend which did not reach statistical significance with our sample size. Shorter duration burns m a y be safer in patients with preexisting tractional elevation o f the retina since it was less c o m m o n for these eyes to develop progression o f traction retinal detachments or new traction retinal detachments.
Acknowledgements. This project was supported in part by the Bascorn Palmer Eye Institute, Department of Ophthalmology, University of Miami, and the patients and contributors of the Department of Ophthalmology at Penn State College of Medicine; Research to Prevent Blindness. Inc., New York City; Florida Lions Eye Bank Laboratory and the Benn Green Diabetic Retinopathy Fund, Miami, Florida. References 1. Blankenship GW (1986) Red krypton and blue-green argon panretinal laser photocoagulation for proliferative diabetic retinopathy: a laboratory and clinical comparison. Trans Am Ophthalmol Soc 84: 967-1003 2. Blankenship GW (1988) A clinical comparison of central and peripheral argon laser panretinal photocoagulation for proliferative diabetic retinopathy. Ophthalmology 95 : 170-177
3. Diabetic Retinopathy Study Research Group (1976) Preliminary report on effects of photocoagulafion therapy. Am J Ophthalmol 81:383-396 4. Diabetic Refinopathy Study Research Group (1978) Photocoagulafion treatment of proliferative diabetic retinopathy; the second report of the DRS findings. Ophthalmology 85:82-106 5. Diabetic Retinopathy Study Research Group (1979) Four risk factors for severe visual loss in diabetic refinopathy: the third report from the DRS. Arch Ophthalmol 97:654-655 6. Diabetic Retinopathy Study Research Group (1981) Photocoagulation treatment of proliferative diabetic retinopathy: clinical application of DRS findings, DRS report number 8. Ophthalmology 88 : 583-600 7. Doft BH, Blankenship GW (1982) Single versus multiple treatment sessions of argon laser panretinal photocoagulation for proliferative diabetic retinopathy. Ophthalmology 89 : 772-779 8. Ferris FL, Podgor MJ, Davis MD, Diabetic Retinopathy Study Research Group (1987) Macular edema in diabetic retinopathy study patients. Diabetic Retinopathy Study Report Number 12. Ophthalmology 94: 754-760 9. Little HL (1983) Proliferative diabetic retinopathy: pathogenesis and treatment. In: Little HL, Jack RL, Patz A, Forsham PH (eds) Diabetic retinopathy. Thieme-Stratton, New York, pp 257-273 10. McDonald HR, Schatz H (1985) Visual loss following panrefinal photocoagulation for proliferative diabetic retinopathy. Ophthalmology 92:388-393 11. McDonald HR, Schatz H (1985) Macular edema following panretinal photocoagulation. Retina 5 : 5-10 12. Meyers SM (1980) Macular edema after scatter laser photocoagulation for proliferative diabetic retinopathy. Am J Ophthalmol 90 : 519-524 13. Molnar J, Poitry S, Tsacopoulos M, Giladi N, Leuenberger PM (1985) Effect of laser photocoagulation on oxygenation of the retina in miniature pigs. Invest Ophthalmol Vis Sci 26:1410-1414 14. Stefansson E, HatcheU DL, Fisher BL, Sutherland FS, Machemer R (1986) Panretinal photocoagulation and retinal oxygenation in normal and diabetic cats. Am J Ophthalmol 101 : 657-664 15. Wallow IHL, Davis MD (1979) Clinicopathologic correlation of xenon arc and argon laser photocoagulation: procedure in human diabetic eyes. Arch Ophthalmol 97:2308-2315 Received May 16, 1989 / Accepted September 28, 1989
Graefe's Arch Clin Exp Ophthalmol (1990)228:226-231
for Clinical and
Experimental
Ophthalmology © Springer-Verlag 1990
The effect of short versus long exposure times of argon laser panretinal photocoagulation on proliferative diabetic retinopathy Edward C. Wade and George W. Blankenship Department of Ophthalmology, Bascom Palmer Eye Institute, University of Miami School of Medicine, Miami, Fla, USA
Abstract. We performed a randomized clinical trial comparing short-duration (0.1 s) with long-duration (0.5 s) bluegreen argon laser burns to deliver panretinal photocoagulation (PRP) in eyes suffering from proliferative diabetic retinopathy with high risk characteristics. We studied 19 eyes in the 0.1-s group and 24 eyes in the 0.5-s group for 6 months. Two or more lines of acuity were lost by 20% of the 0.1-s PRP eyes, but by only 8% of the 0.5-s PRP eyes; New or increased vitreous hemorrhages occurred in 30% of the 0.1-s PRP eyes, but in only 16% of the 0.5-s PRP eyes; New or increased traction retinal detachments did not occur in the 0.l-s PRP eyes, but occurred in 16% of the 0.5-s PRP eyes. There was complete disc neovascular regression in 85% of the 0.1-s PRP eyes and 81% of the 0.5-s PRP eyes. These trends were not statistically significant.
Introduction The Diabetic Retinopathy Study (DRS) [3-6] determined that panretinal photocoagulation (PRP) using blue-green argon or xenon light wave lengths reduces the chance of severe visual loss from proliferative diabetic retinopathy. The mechanism by which PRP induces neovascular regression and prevents further neovascular development, which reduces the risk of severe visual loss, is not known. Laser burns made by different exposure durations produce different chorioretinal scars [15] which may alter the effectiveness of PRP. The treatment effect with longer duration exposure burns may be better, the same, or not as good as the effect obtained with shorter duration burns. This article describes the results of a randomized, prospective, clinical trial evaluating the efficacy and side effects of PRP using short (0.1 s) vs long (0.5 s) exposure time with the blue-green argon laser. Materials and methods Eyes of informed and consenting patients with three or four of the possible four diabetic retinopathy risk factors for severe visual loss as determined by the DRS [5] were Offprint requests to: G.W. Blankenship, Department of Ophthalmology, Pennsylvania State College of Medicine, P.O. Box 850, Hershey, PA 17033, USA
treated with blue-green argon laser PRP. Five hundred micron spots of either short (0.1 s) or long (0.5 s) duration were used with sufficient energy to obtain a moderate blanching of the neurosensory retina overlying the pigment epithelial burn. The burn duration of each case was randomly selected. To be eligible, the patient had to have a diagnosis of diabetes mellitus, be able to return for postlaser examinations at 1 week, i month, and 6 months, and be willing to participate in a random selection of either 0.l-s or 0.5-s burn exposure time. Ocular eligibility criteria of the involved eye required best corrected visual acuity of 6/30 or better, media clarity sufficient for PRP in a single session and three or four diabetic retinopathy risk factors. Eyes with prior photocoagulation, or substantial lens or vitreous opacities sufficient to prevent PRP, were ineligible. The pretreatment examination consisted of obtaining general information regarding the patient's age, sex, race, duration of diabetes, and means of blood glucose control. The eye examination consisted of obtaining a best-corrected visual acuity with a projected Snellen chart, slit lamp examination, applanation tonometry, fundus examination with indirect ophthalmoscopy, and a Hruby lens or 90-D condensing lens. Pretreatment 60 ° stereo color photographs were taken. Macular thickening was present when there was increased width of the slit lamp beam within I disc diameter of the center of the macula. Neovascularization of the disc (NVD) was graded using DRS standard photograph 10A showing one-fourth to one-third disc area surface neovascularization for comparison [3]. Neovascularization elsewhere (NVE) was graded as in the DRS as less than 0.5 disc diameters or more extensive. After the patient had been informed and had consented to participate, a coin was flipped which determined whether the eye was to receive short (0.l-s)- or long (0.5-s)-duration exposure times with the blue-green argon laser. Recruitment and randomization continued until there were 25 treated eyes in the 0.1-s group, with the last two cases in the 0.5-s group being assigned rather than randomized to make an equal number of eyes in each group. The PRP was performed in a single treatment session using retrobulbar anesthesia through a widely dilated pupil. Blue-green argon laser was used with a 500-gm spot size at 0.1- or 0.5-s exposure time using sufficient energy to obtain moderate blanching of the retinal pigment epithelium. A panscopic fundus contact lens was used, and the
227 laser burns were placed around the arcades and 2 disc diameters temporal to the center of the macula extending peripherally as far as possible. The burns were placed approximately one-half burn width apart. The patients randomized to P R P with 0.1-s exposure time had between 650 and 1000 spots (mean 767) produced with power settings from 0.7 to 1.5 W (mean 1.05 W). The 0.5-s P R P group had between 500 and 900 spots (mean 710) produced with power settings from 0.3 to 0.6 W (mean 0.4; Figs. 1, 2, 3). Post-treatment medications were not used for either group. Follow-up examinations identical to the pretreatment examinations were performed at I week, 1 month, and 6 months after treatment, and as indicated by each individual case. Results
Fig. 1. Blue-green argon laser burns (500 pm) produced with 0.l-s (upper burn) and 0.5-s (lower burn) durations
A total of 41 patients participated in the study with 50 eyes receiving treatment. Twenty-five eyes randomized to short (0.l-s) exposure time, and 23 eyes were randomized and 2 were assigned to long (0.5-s) exposure time. Six-month follow-up was available on 20 (80%) of the 25 eyes in the 0.1-s group, and 24 (96%) o f the 25 eyes in the 0.5-s group. Of the five patients (six eyes) unavailable for follow-up, one patient died of a massive gastrointestinal hemorrhage 1 month after PRP, and four patients could not be located. We evaluated the data on 44 eyes with 6-month follow-up.
Pretreatment evaluation The 19 patients randomized to receive 0.1-s P R P consisted of nine (48%) men and ten (52%) women whose ages ranged from 18 to 82 years (mean 48 years). They had Table 1. Numbers of eyes and visual acuities
Fig. 2. Panretinal photocoagulation using 0.1-s duration, 500 gm blue-green argon laser wave lengths
6/6-6/7.5
6/9-6/15
6/18-6/30
_+4
+3-+2
+1---1
--2--3
_>-4
No. (%)
No. (%)
No. (%)
No. (%)
No. (%)
1 Month posttreatment 0.1 s 1 (5) 1 (5) 0.5s 0 (0) 3 (12)
14 (70) 15 (64)
4 5
(20) (20)
0 1
(0) (4)
6 Month posttreatment 0.1 s 1 (5) 2 (10) 0.5 s 3 (12) 5 (20)
13 (65) 14 (60)
2 1
(10) (4)
2 1
(10) (4)
228 Table 3. Change in neovascularization of the disc Pretreatment at 0.1 s None
Pretreatment at 0.5 s >_DRS10A a
None
DRS 10A"
11 1 0
5 1 0
2 0 0
11 4 t
10 2 0
6 0 0
2 0 0
13 3 0
1/2 DA 0 0
8 3 2
9 0 0
0 0 0
10 5 0
I Month posttreatment None < 1/2 DA > I/2 DA
7 0 0
a Disc area
k n o w n of their diabetes for 8-38 years (mean 20 years), and at the time of entering the study, 16 (85%) were receiving insulin a n d 3 (15%) were using oral hypoglycemics. There were 12 (60%) right eyes a n d 8 (40%) left eyes. The 24 patients randomized to receive 0.5-s P R P consisted of 12 (50%) m e n a n d 12 (50%) w o m e n whose ages ranged from 19 to 71 years (mean 49 years). They had k n o w n of their diabetes for 2-40 years (mean 18 years); 21 (88%) were receiving insulin and 3 (12%) were using oral hypoglycemics. There were 9 (35%) right eyes and 15 (65%) left eyes. Pretreatment best-corrected visual acuities for both the 0.1-s a n d 0.5-s P R P eyes are compared with those obtained at i and 6 months after treatment in Tables 1 a n d 2. The cases randomized to 0.l-s P R P had slightly better pretreatment visual acuities. Sixteen eyes (80%) in the 0.l-s P R P group had 6/15 or better pretreatment visual acuity, whereas in the 0.5-s P R P group, only 12 eyes (50%) had 6/15 or better. S u b n o r m a l visual acuity was caused by m i n o r cateracts, vitreous hemorrhages, and macular disease. The pretreatment anterior segment examinations found m i n o r iris neovascularization a r o u n d the pupillary margins in none of the eyes in the 0.l-s P R P group, b u t in one eye in the 0.5-s P R P group. All eyes had intraocular pressures of less t h a n 30. M i n o r vitreous cavity and preretinal hemorrhages were present in 11 (55%) of the 0.l-s P R P and 12 (50%) of the 0.5-s P R P eyes. Macular thickening was present in m a n y of the eyes prior to PRP. F o u r (20%)
of the 0.1-s P R P eyes and eight (34%) of the 0.5-s eyes had some degree of macular thickening. One eye in each group had an epimacular membrane. Extramacular traction detachments were present in two (8%) of the 0A-s eyes a n d in six (25%) of the 0.5-s eyes. N o n e of the eyes in either group had macular detachments. N V D was usually present before PRP. Twelve of the 20 (60%) 0.1-s and 16 of the 24 (67%) 0.5-s P R P eyes had N V D greater or equal to the D R S standard photograph No. 10A (see Figure 1). A n additional two (10%) of the 0.l-s and two (8%) of the 0.5-s P R P eves had less extensive N V D (Table 3). N V E equal to or greater than one-half disc area was present in 13 of 20 (65%) eyes in the 0.1-s and 15 of 24 (63%) eyes in the 0.5-s group (Table 4). Of the eyes r a n d o m l y assigned to 0.1-s PRP, 16 (80%) had 3 retinopathy risk factors, and the remaining 4 (20%) had 4 risk factors. The 0.5-s group had 19 (79%) with 3 risk factors and the remaining 5 (21%) had 4 risk factors [5].
Early postlaser evaluation After panretinal laser photocoagulation there were minor inflammatory changes observed at the day 7 follow-up examination, b u t the prevalence a n d extent of these early side effects in the two groups were similar. One eye in the 0.5-s group, but none in the 0.l-s group, had moderate shallowing of the anterior chamber. None of the eyes in either group had intraocular pressures greater than 30 mmHg. Shallow peripheral choroidal detachments occurred in 1 of 20 (5%) eyes in the 0.l-s group and 4 of 24 (17%) eyes in the 0.5-s group. One eye in each group developed a peripheral exudative retinal detachment without macular involvement that resolved by the visit 1 month. Macular thickening was noted in 9 of 20 (45%) eyes in the 0.1-s group and 9 of 24 (38%) eyes in the 0.5-s group i week after treatment. I n the 0.1-s eyes, all four eyes that had macular thickening prior to P R P had an increase m macular thickening I week after PRP. I n the 0.5-s eyes four of eight eyes with macular thickening prior to P R P developed an increase in macular thickening I week after PRP.
Postlaser treatment evaluation at 1 month The inflammatory reactions present during the first week following PRP had resolved by the post-treatment examinations at 1 month. The best-corrected visual acuities 1 m o n t h after PRP are shown in Table 1. Two (10%) eyes in the
229 0.1-s group had visual acuities of 6/60 or worse. One was due to a preretinal hemorrhage, and the other eye had an opacified posterior lens capsule that improved to 6/7.5 after Nd Y A G capsulotomy. Three 0 2 % ) eyes in the 0.5-s group had visual acuities of 6/60 or worse. One eye developed a combined traction and rhegmatogenous retinal detachment that was subsequently successfully repaired, one eye had increased macular thickening, and the other eye had a macular hole. Table 2 shows the changes of visual acuity from the pretreatment level with the majority of eyes in both groups having changed one line or less. Substantial clearing of pretreatment vitreous hemorrhage was common, and new bleeding was uncommon after PRP. New vitreous or preretinal hemorrhage was present in four (20%) eyes in the 0.1-s PRP group and three (13%) eyes in the 0.5-s PRP group. Most of the increased macular thickening at the 1 week follow-up examination had resolved by I month. Of the nine eyes in the 0.l-s group, only one eye had persistence of the increased macular thickening. Of the nine eyes in the 0.5-s group with increased macular thickening at 1 week, two had persistence of the thickening. The two pretreatment extramacular traction detachments in the 0.1-s group remained the same, but in the 0.5-s group, one of the six (18%) eyes with a pretreatment extramacular traction detachment developed a combined rhegmatogenous and traction retinal detachment as mentioned above. No new traction detachments developed in the 0.1-s group, but 3 of the 18 0 6 % ) eyes in the 0.5-s group without pretreatment traction retinal detachments developed extramacular traction detachments at 1 month. This difference was not statistically significant and would require a sample size of 50 subjects in each group to have an 80% chance of detecting significance at a P = 0.05 level. Disc neovascularization had substantially regressed in both groups (Table 3). Of the eyes with pretreatment NVD equal to or greater than DRS photo 10A, l l of 12 (92%) of the 0.l-s group had no NVD and I (8%) had partial regression, and Ii of 16 (70%) of the 0.5-s group had no NVD, 4 (25%) had partial regression, and the remaining eye (5%) had presistent NVD equal to or greater than DRS photo 10A. One eye in the 0.5-s group that did not have pretreatment NVD developed NVD. The change in NVE is shown in Table 4 with regression of NVE being almost identical for both treatment groups. Postlaser treatment evaluation at 6 months
None of the eyes in either group received additional laser treatment prior to the 6-month follow-up exam, but a pars plana vitrectomy had been performed on one eye in the 0.5-s group that developed a combined rhegmatogenous and traction retinal detachment I month following PRP with successful retinal reattachment. Most of the eyes maintained good visual function with substantial clearing of vitreous hemorrhage and regression of disc and retinal neovascularization, indicating a substantially improved prognosis for maintaining good visual function. The best-corrected visual acuities are shown in Table 1. In the 0.l-s group, 80% had 6/15 or better acuities compared with 68% of the 0.5-s eyes. This difference is not statistically significant. The changes in visual acuities are shown in Table 2. Approximately 60% of eyes in both groups stayed within
one line of their pretreatment visual acuities. Improved acuities were more common in the 0.5-s group, and decreased acuities were more common in the 0.l-s group. In the 0.l-s group, three (15%) eyes had improved vision: two improvements were due to vitreous hemorrhage clearing; one was due to a Nd Y A G capsulotomy of an opacified posterior capsule. Eight eyes (32%) in the 0.5-s group had improved six due to vitreous hemorrhage clearing, and two due to decreased macular thickening. This difference was not statistically significant and would require 82 eyes in each group to have an 80% chance of detecting significance at a P = 0.05 level. A decrease in vision was more common in the 0.1-s group. Four (20%) eyes in the 0.1-s group lost two or more lines: three losses were due to vitreous hemorrhage, and one eye had a central retinal artery occlusion. In the 0.5-s group, only two (8%) eyes lost two or more lines: one was the eye with the retinal detachment which had increased cateract after surgery, and the other also had an increased cataract. Iris neovascularization regressed in the one eye in which it was present prior to PRP in the 0.5-s group. No iris neovascularization developed in either group throughout the study. All eyes in both groups maintained intraocular pressures below 30 mmHg throughout the study. There was no significant change in lens opacities throughout the study in either group except for one eye in the 0.1-s group that developed an opacity of the posterior capsule requiring Nd YAG capsulotomy and the two eyes in the 0.5-s group. New or increased preretinal or vitreous hemorrhages were uncommon in both groups, although they were less common in the 0.5-s group. Six of the 20 eyes (30%) in the 0.1-s group had bleeding within 6 months after PRP. All of the hemorrhages cleared without requiring pars plana vitrectomy. Four of the 24 eyes (16%) in the 0.5-s group had vitreous or preretinal hemorrhage, none of which required vitrectomy. This difference was not statistically significant and would require 134 eyes in each group to have an 80% chance of detecting significance at a P = 0.05 level. Macular thickening was present 6 months after PRP in only two eyes in the 0.1-s group, one eye had no change in the pretreatment macular thickening, and one eye having no macular thickening prior to PRP developed mild macular thickening. One of the eyes in the 0.5-s group had less macular thickening at the 6-month exam than before treatment. None of the eyes in either group developed new traction retinal detachments between the 1-month and 6-month examinations. The two extramacular traction retinal detachments present prior to PRP in the 0.1-s group did not progress. The combined traction and rhegmatogenous retinal detachment in the 0.5-s group that developed 1 month following PRP had been successfully repaired, and the other eight extramacular traction detachments remained unchanged. This difference was not statistically significant. There was substantial NVD regression in both groups, and none of the eyes in either group had NVD equal to or greater than DRS photo 10A (Table 3). Of the eyes with pretreatment NVD equal to or greater than DRS photo 10A, 10 of 12 (85%) of the 0.l-s group had no NVD, and 2 (15 %) had partial regression; 13 of 16 (81%) of the 0.5-s group had no NVD, and 3 (19%) had partial regression. This difference was not statistically significant. There was also substantial NVE regression in both groups. Complete
230 NVE regression was accomplished in 8 of the 13 (60%) 0.1-s eyes, and in 10 of the 15 (67%) 0.5-s eyes. Discussion
The DRS findings [3-6) confirmed the benefits of PRP treatment in reducing the incidence of severe visual loss and regressing neovascularization in the majority of eyes with proliferative diabetic retinopathy. The DRS protocol PRP treatment used 800-1600 blue-green argon burns of 500-gm spot size and 0.1-s duration. The mechanism by which PRP causes neovascular regression is not known. Panretinal photocoagulation has been shown to increase preretinal oxygen tension possibly by: (a) thinning the RPE and outer retinal layers and thereby increasing choroidal oxygen diffusion to the inner retina; and (b) destroying the outer retina and RPE that account for most of the retinal oxygen consumption [13, 14]. The increase in available oxygen to the inner retina may reduce the liberation of an angiogenic factor. Previous histological studies on human eyes have confirmed that 0.5-s, blue-green argon burns produce larger scars and thinning of the retina than 0.1-s burns [15]. Therefore, there is a theoretical, but unproven, consideration that longer duration burns may increase preretinal oxygen tension above the levels seen with shorter burns, thereby reducing the stimulus for angiogenic factor more effectively. The ophthalmoscopic and photographic appearance of the 0.1-s and 0.5-s burns with our treatment were identical. This was accomplished by markedly reducing the energy used with the longer duration burns. This identical appearance and apparent size suggests, but certainly does not prove, that the burns were of equal intensity and involved the same volume of retina. Randomization to treatment groups upon entry into the study resulted in both groups being comparable with respect to age, sex, duration of disease, use of insulin, incidence of iris neovascularization, glaucoma, cateracts, vitreous hemorrhages, NVD, NVE, and number of retinopathy risk factors. The 0.l-s group had slightly better pretreatment visual acuities, less macular thickening, and fewer extramacular traction retinal detachments than the 0.5-s group. The number of burns was also comparable. The blue-green argon wave lengths were used in our study to make the findings more comparable to the DRS and other more recent studies. Eliminating the blue wave length component of argon laser may reduce intraretinal energy absorption and subsequent scarring and traction, but the results of PRP treatment of diabetic retinopathy with high-risk characteristics using only green argon wave lengths has not been reported. We analyzed several parameters following PRP. Most of the eyes (60%) in both groups maintained visual acuities within one line of the pretreatment level. There was a trend, however, for more eyes in the 0.5-s group (32% vs 15%) to have improved vision at the 6-month exam. Most of these eyes had improved acuities due to clearing of vitreous hemorrhages. Although the prevalence of vitreous hemorrhage prior to PRP was similar in both groups, it was more common for vision to be reduced by vitreous hemorrhage prior to PRP in the 0.5-s group, leaving more room for improvement over the following 6 months. Thus, apparent greater frequency of improved vision in the 0.5-s group may be due to their poorer pretreatment acuities.
A decrease in visual acuity of two or more lines 6 months pos.t-PRP was more common in the 0.l-s than in the 0.5-s group (20% vs 8%). In the 0.1-s group, this was due to vitreous hemorrhages in three eyes and a central retinal artery occlusion in one eye. In the 0.5-s group, one eye developed a combined traction and rhegmatogenous retinal detachment which was successfully repaired but developed a dense cataract, and one eye had a progressive cataract. McDonald and Schatz [10] treated eyes with 0.05-s duration burns and had a 28% prevalence of visual loss in patients followed for 3-12 months, which is similar to what we found in our 0.1-s group, but three times greater than results from our 0.5-s group. Most of the patients in their series lost vision from macular thickening and vitreous hemorrhages. In the DRS [4], 15% of 0.1-s argontreated eyes had a similar visual loss of tow lines or more 4 months after treatment. Two or more lines of vision were lost in 24% of the eyes in a single vs multiple treatment clinical trial [7], 17% of the eyes in an argon vs krypton clinical trial [1], 24% of the eyes in the central PRP, and 8% of the eyes in the peripheral PRP clinical trial [2]. All of these trials used 0.1-s burns except for the krypton treated eyes which were treated with 0.2-s burns. New or increased preretinal or vitreous hemorrhages were more common in the 0.l-s than in the 0.5-s group (30% vs 16%). In both groups, NVD and NVE regressed equally; however, the neovascularization that persisted in the 0.1-s eyes was more likely to bleed. New vitreous hemorrhages occurred in I 4 % - 2 8 % of eyes in previous series [1, 2, 71. Both treatment groups had better NVD and NVE regression than those in previous reports. Complete regression of pretreatment N V D equal to or greater than DRS standard photo 10A occurred in 85% of the 0.1-s eyes and 81% of the 0.5-s eyes. In the DRS [4], similar complete regression of extensive disc neovascularization was observed in only 29.8% of 188 eyes 12 months after treatment. Little's [9] series found 50% of eyes with similar NVD had complete regression. Complete regression of similar NVD was observed in 49% of the eyes in the single vs multiple session trial [7], 56% of eyes in the argon vs krypton trial [1], and 43% of the eyes in the central vs peripheral trial
[2]. Macular thickening was present in four (20%) eyes in the 0.l-s and eight (34%) eyes in the 0.5-s group before treatment. One week after PRP, macular thickening was present in nine eyes in each group. All four of the 0.1-s eyes with pretreatment macular thickening had increased thickening, and four of eight 0.5-s eyes with pretreatment thickening had increased thickening 1 week after PRP. This agrees with previous observations that eyes with macular thickening prior to PRP are more likely to develop an increase in the thickening following PRP [8, 10-12]; At the 1 month exam, macular thickening had improved in most eyes. Only one 0.1-s eye and two 0.5-s eyes had macular thickening. By the 6 month exam, two (10%) 0.1-s eyes and one (4%) 0.5-s eye had macular thickening:. This is in contrast to the report by McDonald and Schatz [14] who found persistent macular edema for 8-32 months following PRP in 47 (27%) of 175 eyes. Only 16 (8%) of 175 eyes lost vision due to persistent macular edema. Their prevalence may be higher because they performed fluorescein angiography on follow-up examinations which may increase the sensitivity of diagnosing mild macular edema.
231 There were no new traction retinal detachment or p r o gression o f pretreatment traction retinal detachments in the 0.l-s eyes. One o f the six 0.5-s eyes with a pretreatment extramacular traction retinal detachment developed a combined traction and rhegmatogenous retinal detachment involving the m a c u l a 1 m o n t h after PRP. Three 0.5-s eyes developed new traction retinal detachments; none o f these involved the macula. The findings o f this prospective, randomized clinical trial comparing 0.1-s with 0.5-s blue-green argon laser P R P in eyes suffering from proliferative diabetic retinopathy with high-risk characteristics indicate that b o t h treatments are effective in achieving regression o f disc and retinal neovascularization and in maintaining stable vision in the maj o r i t y o f eyes. The slightly lower prevalence o f new vitreous or preretinal hemorrhages as well as the lower prevalence o f loss o f two or m o r e lines o f visual acuity in the 0.5-s eyes indicates that longer duration burns m a y be m o r e effective in the treatment o f proliferative diabetic retinopathy; however, this was only a trend which did not reach statistical significance with our sample size. Shorter duration burns m a y be safer in patients with preexisting tractional elevation o f the retina since it was less c o m m o n for these eyes to develop progression o f traction retinal detachments or new traction retinal detachments.
Acknowledgements. This project was supported in part by the Bascorn Palmer Eye Institute, Department of Ophthalmology, University of Miami, and the patients and contributors of the Department of Ophthalmology at Penn State College of Medicine; Research to Prevent Blindness. Inc., New York City; Florida Lions Eye Bank Laboratory and the Benn Green Diabetic Retinopathy Fund, Miami, Florida. References 1. Blankenship GW (1986) Red krypton and blue-green argon panretinal laser photocoagulation for proliferative diabetic retinopathy: a laboratory and clinical comparison. Trans Am Ophthalmol Soc 84: 967-1003 2. Blankenship GW (1988) A clinical comparison of central and peripheral argon laser panretinal photocoagulation for proliferative diabetic retinopathy. Ophthalmology 95 : 170-177
3. Diabetic Retinopathy Study Research Group (1976) Preliminary report on effects of photocoagulafion therapy. Am J Ophthalmol 81:383-396 4. Diabetic Refinopathy Study Research Group (1978) Photocoagulafion treatment of proliferative diabetic retinopathy; the second report of the DRS findings. Ophthalmology 85:82-106 5. Diabetic Retinopathy Study Research Group (1979) Four risk factors for severe visual loss in diabetic refinopathy: the third report from the DRS. Arch Ophthalmol 97:654-655 6. Diabetic Retinopathy Study Research Group (1981) Photocoagulation treatment of proliferative diabetic retinopathy: clinical application of DRS findings, DRS report number 8. Ophthalmology 88 : 583-600 7. Doft BH, Blankenship GW (1982) Single versus multiple treatment sessions of argon laser panretinal photocoagulation for proliferative diabetic retinopathy. Ophthalmology 89 : 772-779 8. Ferris FL, Podgor MJ, Davis MD, Diabetic Retinopathy Study Research Group (1987) Macular edema in diabetic retinopathy study patients. Diabetic Retinopathy Study Report Number 12. Ophthalmology 94: 754-760 9. Little HL (1983) Proliferative diabetic retinopathy: pathogenesis and treatment. In: Little HL, Jack RL, Patz A, Forsham PH (eds) Diabetic retinopathy. Thieme-Stratton, New York, pp 257-273 10. McDonald HR, Schatz H (1985) Visual loss following panrefinal photocoagulation for proliferative diabetic retinopathy. Ophthalmology 92:388-393 11. McDonald HR, Schatz H (1985) Macular edema following panretinal photocoagulation. Retina 5 : 5-10 12. Meyers SM (1980) Macular edema after scatter laser photocoagulation for proliferative diabetic retinopathy. Am J Ophthalmol 90 : 519-524 13. Molnar J, Poitry S, Tsacopoulos M, Giladi N, Leuenberger PM (1985) Effect of laser photocoagulation on oxygenation of the retina in miniature pigs. Invest Ophthalmol Vis Sci 26:1410-1414 14. Stefansson E, HatcheU DL, Fisher BL, Sutherland FS, Machemer R (1986) Panretinal photocoagulation and retinal oxygenation in normal and diabetic cats. Am J Ophthalmol 101 : 657-664 15. Wallow IHL, Davis MD (1979) Clinicopathologic correlation of xenon arc and argon laser photocoagulation: procedure in human diabetic eyes. Arch Ophthalmol 97:2308-2315 Received May 16, 1989 / Accepted September 28, 1989
