Treatment of Proliferative Diabetic Retinopathy Long-term Results of Argon Laser Photocoagulation HUNTER L. LITTLE, MD
Abstract: Panretinal photocoagulation (PRP) is the treatment of choice for proliferative diabetic retinopathy. Indications for treatment are the presence of disc new vessels or the presence of new vessels elsewhere with hemorrhage. Rubeosis iridis and retinal neovascularization undergo involution following panretinal photocoagulation. The long-term visual results are excellent excepting for eyes with diffuse diabetic retinal ischemia. Long-term follow-up and repeat photocoagulation as needed are advised. [Key words: argon laser, diffuse diabetic retinal ischemia, indications, long-term results, panretinal photocoagulation, proliferative diabetic retinopathy, rubeosis iridis, technique.] Ophthalmology 92:279-283, 1985
Proliferative diabetic retinopathy is the growth of fibrous and vascular .tissue on the retina or optic disc which may extend onto the posterior hyaloid face. It poses a threat of blindness through hemorrhage and retinal detachment. As documented by Shimizu et al, proliferative retinopathy occurs in association with retinal ischemia recognized as nonperfused zones on fluorescein angiography.1 Even though the mode of action is subject to debate, photocoagulation directed to the nonperfused zones of retina commonly noted to extend from the vascular arcades to the periphery (Figs 1, 2) results in regression of fibrovascular proliferation.
diameter, or hemorrhage when associated with new vessels on the disc (NVD) of any magnitude, or new vessels elsewhere (NVE) 2 in association with epiretinal
INDICATIONS FOR TREATMENT
The indications for photocoagulation are the presence of disc neovascularization greater than one-third disc From the Stanford University School of Medicine. Palo Alto, Palo Alto Retinal Group, Inc., and Zweng Memorial Retinal Research Foundation, Menlo Park, California. Presented at the Eighty·eighth Annual Meeting of the American Academy of Ophthalmology, October 3D-November 3, 1983. Reprint requests to Hunter L. Little, MD, 1225 Crane St., Menlo Park, CA 94205.
Fig 1. Proliferative diabetic retinopathy showing disc neovascularization associated with extensive zones of impaired perfusion of mid-peripheral retinal capillaries on fluorescein angiography.
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PATTERN OF PAN-RETINAL PHOTOCOAGULATION TECHNIQUE
Fig 2. Left, pattern of panretinal photocoagulation with argon laser with the largest number of lesions directed to the mid-peripheral retina. Right, placement of 500 ~tm size burns one-half lesion diameter apart
Fig 3. Pre- and post-treatment appearance of macular pathology and mid-peripheral neovascularization.
or vitreal hemorrhage. Even though unproven to date, photocoagulation seems advisable for eyes with moderate to extensive areas of new vessels elsewhere even in the absence of hemorrhage and for eyes with pre-proliferative characteristics (venous bleeding, intraretinal microangiopathy (IRMA), numerous foci of cotton-wool patches, extensive areas of blot and dot hemorrhages, and extensive zones of nonperfused retina on fluorescein angiography). Panretinal photocoagulation of one eye with observation of the fellow eye until high-risk characteristics develop seems advisable in the latter two situations.
MATERIALS AND METHODS Within the last decade, panretinal photocoagulation (PRP) has become the proven and internationally accepted treatment of proliferative diabetic retinopathy. 3- 6 This technique consists of the placement of photocoag280
ulation lesions from the disc margin anteriorly beyond the equator in all meridians sparing only the macula to which focal leaks are treated with small spot sized lesions of 50, 100, and 200 Jtm (Fig 3). The number of panretinal photocoagulation lesions applied is influenced by the severity of the retinopathy, ie. the extensiveness of the nonperfused zones and the size and extent of neovascularization. Number of lesions range from 1500 to 3000 using the 500 Jtm setting for argon laser and 300 to 500 with the 4.5° setting with the xenon photocoagulator. Lesions are placed adjacent to one another for severe retinopathy and from one-half to one lesion diameter apart in less severe retinopathy. Most physicians prefer argon laser rather than xenon arc photocoagulation because of less post-treatment visual field constriction and greater ease of treatment through the slit-lamp delivery system with the fundus contact lens, which gives binocular viewing. Because of increased macular
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Fig 4. Pre- and post-treatment appearance of disc neovascularization with hemorrhage.
edema and choroidal effusion observed in the author's experience after placement of all lesions during one treatment session, three to five treatment sessions over two weeks are advisable for placement of 1500 to 3000 lesions. Dramatic resolution of neovascularization usually occurs within four to eight weeks (Fig 4). Quiescence of retinopathy is recognized by involution of neovascularization leaving only ghost vessels, regression of venous engorgement and retinal hemorrhages, and pallor of the disc (Fig 5). Since neovascularization may fail to undergo resolution or since it may recur, patients are examined at four- to eight-week intervals until retinopathy is quiescent and at four- to six-month intervals thereafter. Repeat panretinal photocoagulation using 1000 lesions with the 500 .urn setting is indicated for persistent or recurrent neovascularization. Since repeat photocoagulation is painful, retrobulbar analgesia is frequently necessary. Three hundred fifty-one eyes having diabetic retinopathy with disc new vessels greater than one-fourth disc diameter were treated by the late H. Christian Zweng, Robert L. Jack, and the author, and were followed from 5 to 12 years. Eyes were not subgrouped according to magnitude of disc vessels, presence or absence of new vessels elsewhere, and presence or absence of preretinal or vitreal hemorrhage. One hundred ninety-six eyes of 122 females and 15 5 eyes of 86 males were treated. The average age at the time of initial laser photocoagulation was 41 and 40 for females and males, respectively, and the mean duration of diabetes was 19 years for both sexes. The mean duration of follow-up was seven years. Each eye received an average of 3181 500 .urn burns with the Coherent 800 or 900 slit-lamp argon laser photocoagulator delivered through the Goldmann 3mirror fundus contact lens. Nonfoveal focal macular hemorrhages, microaneurysms, and leaks on fluorescein angiography were treated with 50, 100, and 200 .urn burns.
Fig 5. Quiescent retinopathy after panretinal photocoagulation.
Best corrected distant visual acuities were measured on the American Optical projector acuity chart with Snellen type letters by experienced ophthalmic technicians under similar conditions over the course of the study. SUPPLEMENTAL TREATMENT TECHNIQUES AND SPECIAL SITUATIONS
Unusual treatment situations deserve special comment. Feeder vessel technique. When neovascularization persists after repeated attempts with panretinal photocoagulation and when associated with engorgement of the new vessels or hemorrhage, the feeder vessels to the neovascular tufts should be treated. Once the feeder vessels have been identified with angiography or with direct observation of corpuscular flow while pressing on the eye, they are treated with the 50 .urn spot diameter, 150 to 200 mW for 0.2 seconds. After closure of the 281
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Fig 6. Auorescein angiogram of right and left eye of patient with diffuse diabetic retinal ischemia shows bilateral extensive nonperfusion of entire retina including maculae. Neovascularization occurred at disc and adjacent vessels. Rubeosis iridis in the right eye occurred in spite of bilateral panretinal photocoagulation.
feeder vessels, the distal portion of the frond is coagulated using 200 JLm diameter lesions, 150 to 200 m W for 0.2 seconds. Walling off traction retinal detachment. For eyes having traction retinal detachments threatening, but not involving, the macula, a double to quadruple barrier rows of 500 JLm-sized lesions have been placed around the area of traction detachment to prevent extension of the detachment into the macula. No retinal tears have occurred as a result of this procedure. Use of krypton panretinal photocoagulation. For eyes with persistent vitreous hemorrhage in spite of 48 hours of head elevation with binocular pin holes or occlusion, panretinal argon laser treatment of the visible peripheral retina combined with krypton red panretinal photocoagulation through semi-transparent vitreous hemorrhage usually results in resolution of retinopathy and hemorrhage. The reduced absorption of the krypton red light by vitreous hemorrhage enables one to perform krypton PRP under situations when argon laser PRP ·is impossible. Diffuse diabetic retinal ischemia. Diffuse diabetic retinal ischemia deserves special comment because of its poor visual prognosis. This syndrome occurs bilaterally in insulin dependent diabetics and consists of the following characteristics: (1) almost total nonperfusion of retinal capillaries, including the macula, as noted on 282
fluorescein angiography (Fig 6); (2) severe venous engorgement, with sluggish blood flow usually associated with venous beading; (3) diffuse edema of the macula, mid-peripheral, and peripheral retina; (4) presence of disc neovascularization with minimal to no retinal neovascularization elsewhere; and (5) frequent occurrence of rubeosis iridis. Due to the loss of transparency, the edematous nonperfused midperipheral retina has a distinctive amorphous picture with loss of visible retinal pigment epithelial and choroidal patterns. Duplication of the veins is common, suggestive of endothelial proliferation within the lumen of large vessels. With the exception of shunt vessels, the entire retinal capillary bed shows impaired perfusion on angiography. The nonperfused macula usually exhibits cystoid edema. The remaining retinal capillaries and vessels coursing adjacent to or across zones of impaired perfusion leak profusely on angiography. Photocoagulation of this condition is extremely difficult because of the retinal edema, which interferes with passage of light through the retina to the retina pigment epithelium; hence, one must repeat panretinal photocoagulation after several weeks when the retina is less edematous. Furthermore, choroidal effusion and increased macular edema occur commonly after extensive photocoagulation. By repeating the process, quiescence of retinopathy and of rubeosis can be achieved in some
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eyes. In spite of a loss of macular function, every effort should be made to save these eyes. However, many of these eyes are lost due to disc vessels with hemorrhage, traction retinal detachment, or rubeosis iridis with neovascular glaucoma. Furthermore, if vitrectomy is done, almost all of these eyes are lost because of neovascular glaucoma. Vitrectomy should never be attempted without prior extensive panretinal photocoagulation or panretinal transcleral cryosurgery or diathermy treatment. Perhaps hypophysectomy should be done for these individuals when retinopathy fails to regress after PRP, and before vision is lost.
RESULTS The long term visual results after panretinal argon laser photocoagulation (PRP) for eyes with disc new vessels are most encouraging. The cumulative visual results for 351 eyes, followed from 5 to 12 years, are given in Table 1. Seventy-five percent of eyes had 20/ 100 or better visual acuity after a 5 to 12 year followup and 60% maintained 20/50 or better vision. Similar encouraging results were noted for the 66 eyes followed from 10 to 12 years after PRP for disc neovascularization, where 67% maintained visual acuity 20/50 or better Table 1. Pre- and Post-treatment Visual Acuities of 351 eyes treated with Panretinal Argon Laser Photocoagulation for Proliferative Diabetic Retinopathy with Disc Neovascularization, Five- to Twelve-Year Follow-up No. Patients Visual Acuity
Initial
20/15 20/20 20/25 20/30 20/40 20/50 20/60 20/70 20/80 20/100 20/200 20/300 20/400 CF HM LP NLP
25 87 51 63 40 16 10 7 8 9 15 3 6 7 4 0 0
Cumulative (%) 25 112 163 226 266 282 292 299 307 316 331 334 340 347 351
(7) (32) (46) (64) (76) (80) (83) (85) (87) (90) (94) (95) (97) (99) (100)
Final
Cumulative (%)
4 38 57 43 37 33 22 9 9 7 23 5 14 15 12 6 17
4 (1) 42 (12) 99 (28) 142 (40) 179 (51) 212 (60) 234 (67) 243 (69) 252 (71) 259 (74) 282 (80) 287 (82) 301 (86) 316 (90) 328 (93) 334 (95) 351 (100)
Total no. males: 86 persons; 155 eyes. Total no. females: 122 persons; 196 eyes. Average age: 40 years. CF = count fingers: HM = hand motions; LP = light perception; NLP = no light perception.
Table 2. Pre- and Post-treatment Visual Acuities of 66 Eyes Treated with Panretinal Photocoagulation for Diabetic Retinopathy with Disc Neovascularization, 10 to 12-year Follow-up No. Patients
Visual Acuity
Initial
Cumulative (%)
Final
Cumulative (%)
20/15 20/20 20/25 20/30 20/40 20/50 20/60 20/70 20/80 20/100 20/200 20/400 CF HM LP NLP
3 22 11 12 11 2 2 0 1 0 2 0 0 0 0 0
3 (5) 25 (38) 36 (55) 48 (73) 59 (89) 61 (92) 63 (95) 63 (95) 64 (97) 64 (97) 66 (100) 66 (100) 66 (100) 66 (100) 66 (100) 66 (100)
0 9 10 14 4 7 4 2 2 3 4 2 0 2 0 3
0 (0) 9 (14) 19 (29) 33 (50) 37 (56) 44 (67) 48 (73) 50 (76) 52 (79) 55 (83) 59 (89) 61 (92) 61 (92) 63 (95) 63 (95) 66 (100)
Total no. males: 36 eyes; 25 persons. Total no. females: 30 eyes; 21 persons. Average age: 37.5 years. CF = count fingers; HM = hand motions; LP = light perception; NLP = no light perception.
(Table 2). Fourteen percent of eyes followed over five years and eight percent of those followed over ten years had less than 20/400. Even though rubeosis usually regresses after PRP, neovascular glaucoma was the major cause of visual failure, occurring in 6% of eyes; traction retinal detachments occurred in 5% of eyes. Successful visual results require long-term follow-up with repeat photocoagulation to recurrent neovascularization and macular leaks. In the author's experience, panretinal photocoagulation reduces the incidence of neovascular glaucoma for eyes that undergo vitrectomy, and it enhances involution of rubeosis irides when the media permits treatment.
REFERENCES 1. Shimizu K, Kobayashi Y, Muraoka K. Midperipheral fundus involve· ment in diabetic retinopathy. Ophthalmology 1981; 88:601-12. 2. Diabetic Retinopathy Study Research Group. Four risk factors for severe visual loss in diabetic retinopathy; the third report from the diabetic retinopathy study. Arch Ophthalmol 1979; 97:654-5. 3. Little HL. Argon laser therapy of diabetic retinopathy. Doc Ophthalmol Proc Ser 1973; 1:77-84. 4. Little HL, Zweng HC, Jack RL, Vassiliadis A. Techniques of argon laser photocoagulation of diabetic disk new vessels. Am J Ophthalmol 1976; 82:675-83. 5. Diabetic Retinopathy Study Research Group. Preliminary report on effects of photocoagulation therapy. Am J Ophthalmol1976; 81:38396.
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