Photocoagulation in Diabetic Retinopathy

A M E R I C A N J O U R N A L OF OPHTHALMOLOGY VOLUME 72

AUGUST, 1971

NUMBER 2

PHOTOCOAGULATION IN DIABETIC R E T I N O P A T H Y A. E. KRILL, M.D., D. B. ARCHER, F.R.C.S., F. W. NEWELL, M.D. AND M. I. C H I S H T I ,

M.D.

Chicago, Illinois

80-20/30 vision). Visual acuities for all pa­ tients before and after treatment are shown in the table. Ocular evaluation—In addition to routine examination, this included: perimetry with the Goldmann perimeter where possible; color photography with the Zeiss fundus camera; fluorescein angiography1 when the media were sufficiently clear; drawings of fundi which could not be photographed or which had significant pathology in the pe­ MATERIALS AND METHODS ripheral fundus. Each patient's eyegrounds Pertinent parameters of these patients' di­ were assessed according to a classification abetic histories, vision, and ocular findings developed at a symposium on the treatment are recorded in Table 1. These include age at of diabetic retinopathy held in Warrenton, which diabetes was diagnosed, age at which Virginia, in 1968. This classification, which retinopathy was first observed, age at treat­ is described in detail elsewhere,2 is now re­ ment, visual acuity before photocoagulation ferred to as the Airlie classification (Fig. and at final follow-up visit, duration of !)• follow-up, and classification data. ThirtyIn the great majority of cases, photo­ three patients were followed for 12 to 23 graphs were used for evaluation. However, months, 14 for 24 to 35 months, and nine pa­ 23 eyes could not be classified because of tients for 36 to 48 months. dense vitreous hemorrhage, massive far-ad­ Twelve patients had vision of 20/60 or vanced proliferative retinopathy, or a combi­ better in each eye. Twenty-four patients had nation of both. vision of 20/60 or better in one eye and 20/ Proliferative retinopathy was present in 100 or worse in the other eye. Sixteen pa­ both eyes of 41 patients and in one eye of tients had vision of 20/100 or worse in both seven patients. Eight patients had nonprolifeyes. The four remaining patients did not fit erative retinopathy in both eyes. We consid­ readily into any of the groups (two had 2 0 / ered the degree of elevation in the designa­ 80-20/200 vision; the other two had 2 0 / tion of proliferative retinopathy as early, moderate, or advanced. Proliferative reti­ From the Eye Research Laboratories, University nopathy ( P R ) within one-fourth disk diame­ of Chicago. This study was supported in part by Public Health Service Grants EY-0S23-09, EY-0277- ter of surface of attached retina was consid­ 05, and RR-5S. ered to be early; P R extending anterior to Reprint requests to Alex E. Krill, M.D., Eye Re­ the retina's normal position by one-fourth to search Laboratories, University of Chicago, 950 two disk diameters was considered to be East 59th Street, Chicago, Illinois 60637. In 1966 we initiated a controlled study of the treatment of diabetic retinopathy by means of retinal photocoagulation in which we treated one eye and followed the natural course of the disease in the untreated eye. Fifty-six of these patients have been followed for one year or more after treat­ ment and their cases are considered to be of value in assessing the effects of photocoagu­ lation.

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CO

8

TABLE 1 CLASSIFICATION* Nonproliferative Case No., Age, and Sex 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11. 12. 13. 14. 15. 16. 17. 18. 19. 20. 21. 22. 23. 24. 25. 26. 27. 28. 29.

50—M 57—F 61—F 56—F 73—F 61—F 48—F 52—M 27—F 56—M 64—F 66—M 60—M 51—M 58—F 18—F 40—M 47—F 75—F 34—F 59—M 59—F 29—F 65—M 30—M 60—M 47—F 65—F 61—F

Age at Onset of Diabetes

Age at Onset of Visual Disturbance

29 33 37 46 40 48 32 47 16 29 59 63 33 32 30 3 21 37 58 17 56 39 8 49 13 44 44 56 50

47 56 58 S3 70 59 45 50 23 46 62 64 57 49 50 17 40 45 70 26 56 56 28 63 27 54 46 62 59

UEt

FX 14 1 6 U

u2 . 5 6.5 U 5.5 5 4.5 2 5.5 U U

l 6

u u3 . 5 6.5 U 5.5 2.5 4.5 2 8 U

u u7 . 5 u3 . 5 2 4.5 3.5 4 U 5 3.5 6 U

u3 U

u

U 5 U U

u u 4 4 U

u4 . 5 u u

TEt F 1 5 U 2 6.5 6.5 2 7 1 4 3.5 7 3.5 5.5 U 7.5 3.5 5 4.5 3.5 7 5.5 3 4.5 4 3.5 4.5 8 5.5

L

ut

2 0 2 4.5 6 2.5 3 0 3 2 1.5 1.5 2.5

u2 1.5 0.5 2.5 2.5

u 3 2.5 3.5 U 0 5 1.5 5

Preretinal

Proliferative UE F

L

F

0 8 U U 0 0

0 8 U

4 1 U 2 4 0 4 0 6 0 2 2 4 4 U 8 3 0 2 4 4 4 0 0 8 4 5 6 7

u3 0

u0 u0 8 0 0 0

UE

TE

8 0 0 4 U

u u u u8 u6 2 u 0 3 8 u 6 u u u 2 u 0 1 0

0

u u4 u u

u u5 u u

Vitreous Hemorrhage

TE

L

F

L

F

U 0 0 4 3 0 3 0 2 0 0 1 4 0

0 0

0 0

3 0

L

U 1 0 0 0 2 0 0 0 1 0 0 0 6 0 0 0 0 0 0 0 0 5 0 0

u u u u u 0 0 0

u0 6 0 0 0

2 6 0 0 0 0 1

F

L

0 9 U

0 0 U U 0 0 9 0 0 0 0 0

u0 0 9 0 4.5 0 0 0 9

u u u u u u4 u3 u0 u6 u0 u0 0 0 u 20 10 00 0 0 0 0 6 u 00 01 98 5 6 0 u6 u0 u6 ui u0 U0 1 0

0 0

u u u6 u u

0 8 1 8

0 0

u u0 u u

0 0 3 0 0 0

0 0

u

0 0 0 1 5

0 0 9

u9 U

u

Acuities

TE

UE

u u u4 . 5 9 0

u

9 U 9 0 0 U U 4.5 U U

F 4.5 3 U 0 4.5 0 0 0 4.5 0 4.5 0 4.5 4.5 U 4.5 4.5 0 0 0 4.5 0 4.5 0 9 0 4.5 4.5 4.5

TE

UE L

F

L

F

L

U 0 0 0 0 0 0 0 0 0 0 0 6.5 0

20/20 20/300

20/20

20/200 10/300

10/200 20/200

u0 0 0 0 0

u

0 0 0

CF LP CF

20/200

HM

HM NLP ENC

20/200 5/200 HM

20/60 20/300 20/25 20/30 20/60

20/25 20/25 20/60

20/100 20/300 10/300 20/60 20/60

20/60 20/70 20/80

CF

LP

20/40 CF

LP CF CF

LP

20/200

20/60

20/300 20/80 20/200

20/30 20/100

HM

u 4.5

LP LP

4.5 0 4.5

10/200 20/200

HM

CF HM

NLP NLP

20/30 NLP HM

CF

HM

20/30 20/200 20/80 20/40 20/100 5/200 20/20 20/60 20/300 20/60 20/60

20/30 20/200 5/200 20/25 20/40 10/200 20/25 20/40 20/80

20/60 20/60 20/200 20/200 20/25 15/300 20/60 20/20 20/80

20/40 20/25 20/80 20/200 20/20

20/30 20/40 20/200 20/200

20/20

HM

CF

CF

20/40 ENC

LP

20/60 20/30 20/80 CF

CF

20/60 HM

Follow-up ■ in Months 24 12 40 26 30 12 33 12 13 12 12 15 30 20 26 13 12 23 16 12 21 48 12 14 24 42 15 33 15

> g

w w 2

oC

"—1

>

o^ o►d K H

X > r K O

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O TABLE: l {Continued) Nonproliferati v e Case No., Age, and Sex 30. 56—F 31. 57—F 32. 48—F 33. 58— M 34. 48—F 35. 59—M 36. 36—M 37. 62—M 38. 39—F 39. 53—F 40. 53—F 41. 47—F 42. 51—F 43. 54—M 44. 56—F 45. 50—F 46. 41—M 47. 58—M 48. 65—F 49. 66—M 50. 54—F 51. 38—M 52. 52—F 53. 61—F 54. 53—M 55. 62—F 56. 66—M

Age at Onset of Diabetes 53 55 20 51 36 54 16 59 12 30 23 26 31 27 20 36 17 24 52 62 10 6 23 49 20 43 4

Age at Onset of Visual Disturbance 55 55 41 51 46 57 33 61 38 48 48 46 49 51 55 47 37 55 64 63 52 36 49 60 51 59 43

UEt

Ft

14

6.5 4 4 5 3.5 0.5 3.5 U 3 5.5 0 . 5 1.5 4.5 5.5 1.5 0 . 5 U U U

u u

u u 2

1.5 U U 5 U 5 7 1.5 4 3 6 U 4.5 2

—

2.5 U

u u u u 6

3.5 U 3 U U

u 2 u

Proliferative UE

TEt F 5.5 5.5 3.5

r.5

5 8 5.5 6.5 2 3 U 3.5 2.5 2 6 4 2.5 2 4.5 7 0.5 2 2 8 2.5 5 4

TE

UE

L

F

L

F

L

2.5 1.5 0 U 0.5 2 U 2 0.5 1 U

2 0 2 U 4 3 2 0 0 U

0 2 0 U U U 5 0 3

2 2 0 U 8 2 5 0 0 0

5 U

U

2 2 4 6 2 2 8 0 3 1 U 2 5 2 0 6 4 8 0 0 2 2 3 6 4 6 4

—

U 3 4 0.5 U 0 2 0 3 U 2 6.5 1 0 3.5

u u u 8 u 2 6 u u u u u

8 U 2 2 0 0 5 U 8 8 4 6 2 U U U 5 5 1 U

F L 0 0 0

u

0 6 0 0 0

0 2 0 U

u u 0

0 0

TE F

L

0 0 0 1 0 0 0 4 1 0 0 4 4 0 0 0 0 0 2 U 0 6 0 4 0 0 0 6 0 0 6 0 0 4 0 0 1 0 2 0 2 2 2 0 0 2 0 0 0

u

0 0 4.5 0 4.5 9 0 0 0

L 0 0 0 U

u 9 0 0 0 U U 9 4.5 U U U

0 0 0 0 3

0 2 3 6

u u u 0 0 0 u

u

0 0 4.5 4.5 4.5 9 4.5 4.5

0 9 4.5 9 U 9 0 9

rE

UE

TE

UE F

u u u u9 u8 u6 u0 u u 00 — u 00 . 5 4 u 9 6 u 0 6 9 0 u 3 4.5 u u u u 0 9 U u 9 0 0 4.5 4.5 4 0 0 U 5 5 1 2 1

Acuities

Vitreous Hemorrhage

Preretinal

F

F

0 0 4.5 4.5 4.5 0 4.5 0 4.5 4.5 U 0 4 5.5 0 4.5 0 4.5 4.5 0 0 4.5 0 4.5 4.5 4.5 4

4.5 4.5 0

u

4.5 0 4.5 0 0 4.5 U 4.5 9 3.5 0 0 9 0 4.5 0 0 9 0.5 0 0 0 0

F

F

20/200 20/80 20/80 20/80 20/40 20/30 LP 20/60 HM 20/30 CF

CF

20/60 20/60 20/30

20/60 20/40 20/20

NLP

NLP

20/100 C F 20/100 C F 20/100 20/200 HM 20/25 20/300 L P LP CF CF

10/200

CF

LP LP CF

20/200 20/200 20/60

20/100 20/300 C F CF 20/60 20/60 20/60 20/60 20/80 5/300 C F 20/300 L P

L

F

20/30 20/30 20/40 20/40 20/40 10/300 20/60 20/100 20,30 20/100 20/30 20/25 20/100 20/60 20/60 20/60 20/20 20/25 20/60 10/200 20/30 20/30 20/60 20/60 20/30 20/300 20/300

* A detailed explanation of the point system used to evaluate data in each of the four classification categories can be found in the body of this article under "Results." t UE =Untreated eye, TE =treated eye, U =unclassified. X F=Visit before photocoagulation, L = most recent visit.

20/60 20/60 20/40 LP

20/60 20/200 CF

20/100 20/20 20/200 10/200 20/200 HM

20/80 20/30 20/40 HM

20/25 CF

10/200 20/25 HM

20/30 20/60 20/20 20/300 20/100

Follow-up in Months 12 15 43 44 21 42 20 12 13 21 30 14 27 26 13 40 12 15 15 42 26 15 15 13 12 36 33

O > M H

o

g

H

3 *fl > H X <

o

AMERICAN JOURNAL OF OPHTHALMOLOGY

302

Right ey« ! Left cyn A. NONPROLirKRATIVE

Hemorrhages and/or microaneurysnu "Hard exudates".. "Soft exudates" _ Venous abnormalities Intraretfnal microvaseular abnormalities B. fLOOBKSCBIN

C. FBOLITMBATIT*

D. V1TBXOU8 BBMORKHAGI

« . OTHER OCULAR COMPLICATIONS

i

Fig. 1 (Krill, Archer, Newell, and Chishti). The Airlie classification, showing the recommended form for recording photographic data.

moderate; and PR extending anterior to the retina's normal position by more than two disk diameters was considered to be ad­ vanced. Indications for treatment—In our series, the decision as to which eyes were to be treated was based on the following factors: 1. Bilateral early proliferative retinopathy with preretinal and vitreous hemor­ rhage in one or both eyes. Generally, the eye with the clearest media was treated. 2. Massive vitreous hemorrhage or widespread advanced proliferative retinopathy in one eye combined with either early or moderate proliferative retinopathy, or ad­ vanced localized proliferative retinopathy in the second eye. The better eye was treated. 3. Chronic macular edema with either documented progressive visual loss, or sig­ nificant visual impairment (20/60 or worse) with no improvement on follow-up. To minimize variability in technique, all photocoagulation was done by one person (A.E.K.). The Zeiss photocoagulator was used. The second or third intensity on the overload was used with as short an exposure

AUGUST, 1971

time as possible. The aperture diameter was 4.5 or 6 mm when treating areas outside the macular branches of the superior and infe­ rior temporal vessels, and 3 or 4.5 mm if in­ side these vessels. We tried to obtain a prominent grayish-white reaction outside the macular branches of the superior and infe­ rior temporal vessels, and a fainter gray re­ action within these vessels. The photocoagulation marks were ar­ ranged in a U-shaped configuration with the open end at the optic disk. Two rows of pho­ tocoagulation marks were placed outside the macular branches of the superior and infe­ rior temporal vessels. These areas were joined by a double row of photocoagulation marks crossing over the horizontal raphe about 3 or 4 disk diameters temporal to the fovea. In patients with significant macular edema a single row of photocoagulation burns was placed just inside the macular branches of the temporal vessels, in addition to the above-mentioned areas. This method of photocoagulation included the common sites of neovascularization along­ side the major retinal veins, and their pri­ mary branches, especially those subserving the macula. Areas of surface neovasculariza­ tion outside our selected photocoagulation sites were directly photocoagulated. When new vessels extended into the vitreous, pho­ tocoagulation marks were placed around their base. New vessels on the surface of the optic disk were usually treated by placing photocoagulation marks close to the disk, avoiding the temporal margin. Small prereti­ nal hemorrhages, when distant from a major retinal vessel, were directly photocoagulated. Of the 56 patients photocoagulated, 21 re­ quired retreatment. At the first treatment, 50 or more photocoagulation marks were placed as described above; on retreatment, fewer photocoagulation marks were necessary. Initially, all patients were hospitalized, but eventually most patients were treated on an outpatient basis. Retrobulbar anesthesia was used routinely

VOL. 72, NO. 2

DIABETIC RETINOPATHY

PHOTOGRAPHIC

303

FIELDS

A. Vertical line - perpendicular to the center of the disc.

C. Horizontal line-1 disc diameter below the lower pole of the disc.

B. Horizontal line-4-disc diameter above the upper pole of the disc.

Fig. 2 (Krill, Archer, Newell, and Chishti). Here, the five photographic fields used in the Arlie classi­ fication are outlined. Area 1 is centered on the optic disk. Area 2 is centered on the macula. Area 3 has its nasal limit tangent to the macula and is the area covered temporal to the macula. Area 4 includes the region superior to the macula, and Area S includes the same region inferior to the macula. The nasal limit of these two areas is tangent to a perpendicular line through the center of the disk. The inferior limit of Area 4 is tangent to a horizontal line one-half disk diameter above the upper pole of the optic disk. The upper limit of Area 5 is tangent to a horizontal line one disk diameter below the lower pole of the optic disk (from Goldberg and Fine 2 ).

with initial treatment. When only minimal retreatment was required, anesthesia was of­ ten not needed. RESULTS

The primary parameters assessed before and after treatment were visual acuity and status of the eyegrounds. Changes in vision of at least two lines on the Snellen chart were considered to be significant, as one-line changes may sometimes reflect variations in testing circumstances. In evaluating fundi by the Airlie classifi­ cation (Figs. 1 and 2), we selected what we considered to be the most relevant parameters and weighted each according to our estimate of its importance. The point total for each fundus area con­ sidered was determined by multiplying the Airlie figure (0, 1, 2) by a weighted number (detailed explanation will follow). The total for each category (i.e., nonproliferative, pro-

liferative, preretinal, and vitreous hemor­ rhage) is the sum of the weighted numbers. These figures are shown for each patient in the table. Under nonproliferative aspects in the Airlie classification we evaluated intraretinal hemorrhages, microaneurysms, and edema only in the macula, as these findings are of little visual or prognostic significance else­ where. Each of these parameters was as­ signed a value of 1. Hard exudates were evaluated in the macula and temporal to this region (Area 3). The temporal location was also evaluated because hard exudates at this site are usually an indication of chronic edema in this area, which ultimately may spread to the fovea. Hard exudates in the macula were assigned a value of 1; temporal to this region, a value of one-half. Venous abnormalities above (Area 4) and below (Area 5) the macula, were given a value of

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AMERICAN JOURNAL OF OPHTHALMOLOGY

one-half. Such venous abnormalities may be associated with surface neovascularization, a possible source of preretinal and vitreous hemorrhages. Neovascularization within one disk diam­ eter of the optic disk, a common site for preretinal and vitreal hemorrhage, was given a value of two. Neovascularization above and below the macula was given one point value. (Neovascularization rarely was found to originate in the macula, and therefore this category was eliminated.) Preretinal hemor­ rhages in and below the macula were weighted with a value of two. Vitreous hem­ orrhage was considered to be important in any location; it was given two points at Area 2, one point at Area 1, and one-half point in the other three areas. The four categories used in the Airlie classification, nonproliferative, proliferative, preretinal, and vitreous hanorrhage, are headings in the table. The total points before and after treatment for each eye are shown under these headings. A designation of " U " indicates that classification was impossible (usually because of vitreous hemorrhage). Fluorescein data called for in the Airlie classification are discussed elsewhere in this paper under "Specific beneficial effects of photocoagulation," and also in another publi­ cation.3 In assessing the results of treatment, the patients were grouped in the following man­ ner: 15 patients with early (surface) prolif­ erative retinopathy, 31 patients with moder­ ate to advanced proliferative retinopathy, and 10 patients with nonproliferative reti­ nopathy and macular edema. Evaluation of proliferative retinopathy— A patient was said to have a good result if the treated eye showed an overall improve­ ment or remained static in the proliferative category, while the untreated eye showed de­ terioration or remained severely abnormal due to extensive vitreous hemorrhage or faradvanced proliferative retinopathy. Evaluation of macular edema—A good re­ sult was one in which there was complete or

AUGUST, 1971

almost complete disappearance of macular edema. This was usually associated with a concomitant resolution of intraretinal hem­ orrhage and hard exudates. Early proliferative retinopathy-—Of the 15 patients with early proliferative retinopathy, eight had good results. In five of these eight cases the retinopathy in the treated eye re­ gressed, while that in the untreated eye pro­ gressed. In three of these eight patients, the retinopathy remained static in the treated eye, but deteriorated in the untreated eye. In six other patients with early proliferative retinopathy, photocoagulation did not obvi­ ously retard the progression of the reti­ nopathy. The untreated eye in these cases also deteriorated or remained at a state of ad­ vanced retinopathy. The one remaining pa­ tient in this group showed a more marked improvement of the retinopathy in the un­ treated eye than in the treated eye. Moderate to advanced proliferative retinopathy—Of the 31 patients with moderate to advanced proliferative retinopathy, 18 had good results following photocoagulation. This group was particularly significant as 11 of the untreated eyes had severely abnormal, mostly unclassifiable retinopathy on both ini­ tial and final evaluation. In the remaining 13 patients, three showed deterioration in both eyes, four showed marked deterioration in the treated eye with little change in the un­ treated eye, and in six cases both eyes re­ mained unchanged. Macular edema—In the 10 patients with macular edema and nonproliferative retinop­ athy, the principal changes were partial or complete disappearance of edema, exudates, and intraretinal hemorrhage. One patient de­ veloped advanced proliferative retinopathy in the treated eye. COMBINED VISION AND CLASSIFICATION DATA

The visual and classification data of each patient were assessed together to more accu­ rately appraise the effects of photocoagula­ tion. Results were described as "Good," "Fair,"

VOL. 72, NO. 2

DIABETIC RETINOPATHY

"Poor," and "Inconclusive or difficult to as­ sess." Criteria for a good result was as follows: (1) improvement in vision in the treated eye and deterioration of vision in the untreated eye; (2) improvement of vision in the treated eye with no change of vision in the untreated eye; (3) vision remaining the same in the treated eye with deterioration in the untreated eye; (4) regression of retino­ pathy in the treated eye and progression in the untreated eye; (5) regression of retinopathy in the treated eye and no change in the un­ treated eye; (6) no change in retinopathy in the treated eye with marked deterioration in the untreated eye. A good result based on visual improve­ ment must be accompanied by either im­ provement in retinopathy or no change in the status of the fundus. Similarly, a good result based on improvement of retinopathy must be accompanied by either improvement of vi­ sion or no visual deterioration. A fair result indicates improvement in ei­ ther vision or retinopathy. It is distinguished from a good result in that visual improve­ ment may be accompanied by some deterio­ ration of retinopathy, and, conversely, im­ provement in retinopathy may be associated with slight deterioration of vision. A poor result is one in which there is a significant deterioration of either vision or retinopathy in the treated eye. Inconclusive results included cases with improvement or deterioration in either vision or retinopathy in both eyes. In these cases it was difficult to determine the effects of photocoagulation. The results of treatment were as follows: Twenty-two patients had good results, nine patients had fair results, 15 patients had poor results, and 10 patients had inconclu­ sive results. Of the 10 patients in the last category, seven had improvement in both eyes, and three had deterioration in both eyes. Of the 15 patients with poor results, there were five in which the untreated eye was unclassifiable, both initially and at

305

follow-up. Four patients in this group were legally blind (20/200 or worse) before treat­ ment. SPECIFIC EFFECTS OF PHOTOCOAGULATION

Effects on directly treated and adjacent areas are illustrated in Figures 3-12. These effects may be described as follows: 1. New retinal vessels, both surface and those extending slightly into the vitreous, disappeared six to eight weeks after treat­ ment (compare Figs. 3, 4, 6-A and C). 2. Photocoagulation adjacent to the optic disk often caused atrophy of the new capil­ lary vessels on the disk surface. Occasion­ ally, vessels extending into elevated proliferative growths originating from the disk sur­ face also atrophied, leaving only a fibroglial band (Figs. 5-A and B, 6-A through D, 7-B and D ) . 3. Photocoagulation placed around the base of proliferans extending far into the vitreous often caused atrophy of most or all of the vessels in the proliferative growth (Fig. 8 ) . 4. Waxy exudates and macular edema de­ creased or occasionally completely disap­ peared about two to three months after treat­ ment (Fig. 9 ) . Abnormal retinal vessels in the macular area, although not directly treated, became less permeable after photo­ coagulation to adjacent areas. This is best shown in fluorescein angiography (compare Figs. 10-A and 11-A before photocoagula­ tion with Figs. 10-B and 11-B after photoco­ agulation). In patients with macular edema the maxi­ mum effect was produced when photocoagu­ lation marks were placed inside and outside macular branches of the temporal vessels and temporal to the macula. 5. There was a general decrease in leak­ age from abnormal vasculature in both di­ rectly treated and untreated areas (see before-and-after photocoagulation photographs in Figs. 3, 4, 10, and 11). 6. Intraretinal hemorrhages often disap-

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AMERICAN JOURNAL OF OPHTHALMOLOGY

AUGUST, 1971

Fig. 3 (Krill, Archer, Newell, and Chishti). Right eye of 45-year-old man before photocoagulation show­ ing (A) control photograph of posterior eyegrounds, and fluorescein angiograms during (B) early and (C) late venous stages, and (D) five minutes after injection. In control photograph (A), note extensive neovascularization superior to disk area and along disk surface. Also note superficial retinal hemorrhages, cotton­ wool spots, and waxy exudates. Fluorescein angiograms show widespread areas of capillary nonperfusion, most easily seen during early stages (B and C) of angiography. One such area is indicated by an arrow along superior temporal vessel (B). Extensive capillary dilation, microaneurysms, and shunt vessels are noted in relation to the nonperfused areas. A conglomeration of new vessels, both surface and proliferating into the vitreous, can be seen (B and C) at the upper part of the optic disk extending along the superior temporal vessels. The late angiogram (D) shows profuse dye leakage into the macula and from areas of neovascularization at the optic disk and superior temporal vessels. The superior temporal retinal veins show marked dilation and beading. The vein walls are stained with fluorescein which leaks into the adjacent retina (B, C, andD).

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DIABETIC RETINOPATHY

VOL. 72, NO. 2

A

B

Fig. 4 (Krill, Archer, Newell, and Chishti). Same eye as in Figure 3 shown here five months after photocoagulation. Control photograph (A) may be compared with fluorescein angiograms during (B) early and (C) late venous stages, and (D) five minutes after injection. Note that most of the new surface retinal vessels have disappeared in the superior areas (A, B, and C), both in directly photocoagulated regions and adjacent retina. Most of the hemorrhages in directly treated and adjacent areas have completely disappeared, capillary dilation is now much less evident and the shunt vessels (A and B) are constricted. Many of the capillaries failing to perfuse with dye on previous angiography now appear to be adequately perfused (com­ pare site of arrows in Fig. 3-B and 4-B). There is a dramatic reduction in the area of neovascularization, particularly in the region of the optic disk and along the superotemporal vessels (A, B, and C). Note the considerable reduction in dye leakage in the late angiograms (compare Figs. 3-D and 4-D). There is a marked decrease in caliber of the superotemporal arterioles and veins adjacent to photocoagulation marks (B, C, and D). The superior temporal retinal vein shows absence of beading following photocoagulation, although staining of the vessel wall with fluorescein still occurs (compare Figs. 3-B and 4-B).

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AUGUST, 1971

Fig. 5 (Krill, Archer, Newell, and Chishti). Right and left posterior fundi of 45-year-old man (Case 7). Top: Right eye (A) prior to photocoagulation, and (B) seven months after photocoagulation. Bottom: Left or control eye photographed at the same time as treated eye, both before (C) and (D) seven months after right eye had received photocoagulation. There is a considerable decrease in the caliber of the veins and arterioles of the treated eye, whereas in the untreated eye these vessels have remained the same in size. Note disappearance of vessels on surface of right optic disk. Retinal folds temporal to right disk before photocoagulation have disappeared following treatment. Follow-up revealed a preretinal hemorrhage in­ ferior to the optic disk in untreated eye, whereas the treated eye is free from macular edema and hemorrhage. peared after photocoagulation (Figs. 3, 4, and 6 ) . 7. Microaneurysms, shunts, and areas of capillary dilatation decreased or occasionally disappeared (compare Fig. 10-A with 10-B, 7-A with 7-C, and 3-B with 4-B). Some di­

lated arterioles and venules also appeared to decrease in caliber. 8. In general, areas of capillary nonperfusion (as demonstrated by fluorescein angiography) failed to reopen following photocoag­ ulation. However, in the macula, some non-

VOL. 72, NO. 2

DIABETIC RETINOPATHY

perfused areas did reopen after treatment (compare arrows in Figs. 3-B and 4-B). 9. Many directly treated preretinal hem­ orrhages partially or completely absorbed within 48 to 72 hours following photocoagu­ lation (Fig. 12-A and B ) . 10. Photocoagulation marks frequently

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restricted the spread of preretinal and vitreal hemorrhages, except those originating at the optic disk. 11. Photocoagulation often reduced folds in the retina by causing atrophy of the proliferative fibrous bands producing traction on the retina (Figs. 5 and 8 ) .

Fig. 6 (Krill, Archer, Newell, and Chishti). Photographs of left posterior eyegrounds and macular area from a 19-year-old diabetic woman before (A and B) and six months after (C and D) photocoagulation. Extensive retinitis proliferans is seen at the optic disk and along the superior and inferior temporal vessels prior to photocoagulation (A and B). These vessels have largely disappeared following treatment (C and D). The retinal vessels show an overall decrease in caliber and most of the hemorrhages have disappeared in areas at or adjacent to the sites of photocoagulation (D).

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retinal veins in two patients resulted in reti­ nal hemorrhage. In one patient treatment had to be completed at a later date. 4. Some patients with vitreous retraction GENERAL EFFECTS OF PHOTOCOAGULATION and advanced proliferative retinopathy later Some of the general effects of treatment developed more extensive vitreous retrac­ tion. Perhaps the disease process was accel­ were as follows: erated by photocoagulation in such patients. 1. Reduction in caliber of retinal veins Two aphakic patients developed posterior and arterioles was observed (compare inferotemporal vessels in Fig. 5-A and B). Dilated vitreal traction at the macula with deteriora­ retinal veins occasionally returned to normal tion of central vision after photocoagulation. size (compare Fig. 3-B with 4-B, and 5-A One of these patients received less than the with S-B). Segmentation and beading often usual amount of photocoagulation. Neither became less obvious. Retinal venous circula­ had obvious posterior vitreous disease before tion times improved, but rarely returned to treatment. 5. Mild iridocyclitis was common, but normal. 2. There was disappearance of wide­ only of consequence in one patient who de­ spread areas of neovascularization with a re­ veloped posterior synechiae. It is important placement by fibrous tissue (Figs. 5, 6, and to obtain wide dilation of the pupil before photocoagulation. 7). 6. An effusive retinal detachment of the 3. There was production of a mild optic macula and mid-temporal retina was seen a atrophy and reduction or disappearance of day after photocoagulation in one patient. new vessels on the optic disk surface (com­ Spontaneous absorption of fluid occurred pare Figs. 8-A and C), even when photoco­ within one week and the patient eventually agulation was not directly adjacent to the obtained a good result. disk surface. Extensive disk neovasculariza­ 7. New vessels and fibrous tissue occa­ tion extending into the vitreous was not sig­ nificantly affected by distant photocoagula­ sionally formed adjacent to photocoagulation sites (see arrow in Fig. 10-C). Perhaps this tion. was due to obstruction of small retinal vessels SPECIFIC COMPLICATIONS OF PHOTOCOAGU­ at this site, producing areas of retinal hyLATION poxia. 9. Photocoagulation over an abnormal The specific complications seen in our se­ middle-sized or large retinal vein occasion­ ries of patients are as follows: 1. Inadvertent macular photocoagulation ally produced temporary obstruction ( seen on caused visual loss in one patient. The spread fluorescein angiography). New surface reti­ of heat from the photocoagulation marks nal vessels sometimes formed at the margins caused a foveal scar. (We have also seen loss of such sites, and retreatment was necessary. Conceivably, photocoagulation of the optic of central vision following photocoagulation of the papillomacular bundle in a patient nerve could cause an arcuate scotoma or cen­ tral visual loss if the papillomacular fibers photocoagulated for another disease.4) 2. Small, spotty visual field defects were were damaged. We did not have this compli­ frequently noted as a result of receptor dam­ cation. age at photocoagulated sites. Usually pa­ tients suppressed such scotomas. Arcuate CAUSES OF POOR RESULTS scotomas reflecting nerve fiber damage were Poor results were obtained in 15 patients elicited in a few patients. in our series. Of these, nine patients had 3. Inadvertent photocoagulation of large widespread advanced proliferative retinop12. Photocoagulation often prevented the extension of localized detachments by seal­ ing the edges of such areas.

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athy and vitreal changes at the time of treat­ ment, causing significant posterior retinal traction. It is doubtful whether most of these patients would be considered for treatment at

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present. Four patients were considered to have inadequate photocoagulation. One pa­ tient did well for two and one-half years and then bled severely from a new proliferative

Fig. 7 (Krill, Archer, Newell, Chishti). Fluorescein angiograms of same eye as in Figure 6, shown here before photocoagulation (A and B), and six months afterwards (C and D ) . Photographs at the left (A and C) were taken during mid-retinal venous phase. Photographs at the right (B and D) were taken three minutes after dye injection. Retinitis proliferans is evident along the superotemporal vessels, which show considerable dye leakage in the late picture (B). Following photocoagulation, there is less retinitis proliferans and reduced dye leakage ( D ) . The details of capillary architecture are more distinct following photo­ coagulation (compare Figs. A and C). Note many of the capillaries and hairpin-like dilations have disap­ peared or have become considerably reduced in caliber after photocoagulation (compare arrows in Figs. A and C). The retinal vein walls stain less following treatment, and there is also a reduction in caliber of the venous wall (compare area marked V in Figs. A and C).

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site. It is likely that closer follow-up may have been beneficial in this patient. The cause of a poor result in one patient was unknown. PRECAUTIONARY MEASURES IN PHOTOCOAGULATION

Based on our experience, certain precau­ tions are advised. These are as follows: 1. High intensities should be avoided. Photocoagulation marks within the macula may cause unexpected foveal or papillo-macular bundle damage when high intensities are used. 2. Photocoagulation should be avoided in patients with advanced proliferative retinopathy and extensive posterior eyeground trac­ tion. Treatment may cause further traction and even hole formation and subsequent reti­ nal detachment. 3. It is questionable whether aphakic eyes should be treated, based on our experience with two patients. If used, photocoagulation should be limited or perhaps divided over sev­ eral sessions. 4. Treatment should be avoided, if possi­ ble, in eyes with extensive vitreous hemor­ rhage, even though visibility may be ade­ quate. Eyes with blood in the vitreous often require greater intensities to produce ade­ quate photocoagulation. Such intense photo­ coagulation is more likely to damage the vit­ reous and lead to eventual retraction. It is best, if possible, to limit the amount of treat­ ment in any eye when more than usual en­ ergy is required to produce an adequate burn. Additional photocoagulation can be given at another date. 5. Since vitreous detachment alters the effectiveness of photocoagulation, even in the absence of significant proliferative retinopathy, treatment should be staggered in such areas. 6. One should photocoagulate close to the disk (except, of course, at the temporal mar­ gin) in eyes with extensive optic disk prolif­ eration, even if vessels extend far into the vitreous. Atrophy of the vitreal vessels may occur as a result of such treatment. Exten­

AUGUST, 1971

sive proliferative retinopathy on the optic disk surface is often the source of additional vitreous hemorrhages after photocoagula­ tion, and may be the most frequent cause of failure of treatment. 7. The amount of photocoagulation used is important. It was soon discovered that in order to significantly decrease macular edema it was necessary to photocoagulate in­ side, as well as outside, the macular branches of the temporal vessels. It was also noted that photocoagulation temporal to the macula was necessary to eliminate persistent edema and waxy exudates in this region. If not eliminated, edema in this area sometimes spread directly into the center of the macula. In general, our best results occurred in pa­ tients who had extensive photocoagulation, we believe from the elimination of areas of hypoxic retina. 8. Direct photocoagulation of middle and large sized retinal veins should be avoided. As pointed out, hemorrhage may occur at the time of treatment or partial obstruction of these vessels may result, with the formation of new retinal vessels near such sites. 9. Careful follow-up is essential. Even with initially successful results, new retinal vessel growth may continue to form, particu­ larly near the site of previous photocoagula­ tion. Macular edema may also reappear. Ad­ ditional photocoagulation may be beneficial in such patients. In regard to possible per­ manent remissions observed in patients followed over long periods, it is our impres­ sion that this is more likely to occur with proliferative retinopathy rather than with macular edema, where abnormal retinal ves­ sels may again leak fluid. DISCUSSION

In general, our data support the concept that photocoagulation is of greatest value in eyes with early or moderately advanced pro­ liferative retinopathy.B_" However, in our experience, this treatment may be of value even in far-advanced proliferative retinop­ athy, providing it is localized and not associ-

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ated with significant posterior retinal traction. Photocoagulation has both specific and general effects which should prevent or greatly retard future hemorrhagic episodes,

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These episodes often result in vitreal and proliferative retinal changes with subsequent permanent loss of vision. Furthermore, it is obvious from our data that massive vitreal hemorrhages may take a long time to absorb,

Fig. 8 (Krill, Archer, Newell, Chishti). Photographs of posterior eyegrounds and superotemporal areas of right eye of 47-year-old woman before photocoagulation (A and B) and almost three years afterward (C and D). Note large band-like area of proliferans extending into the vitreous with hemorrhage around and above the proliferative areas (A and B). After photocoagulation, the fibrotic mass is completely de­ void of vessels, as the result of photocoagulation of many sites around the base of the proliferative area (C and D). Some of the retinal vessels are significantly reduced in caliber (compare superotemporal retinal veins and arterioles in Figs. A and C), and some of the tortuosity in the superonasal vessels has diminished (compare Figs. A and C). Most new vessels seen (A) on the surface of the optic disk disappeared following photocoagulation (C), although no photocoagulation burns were applied adjacent to the optic disk. Retinal folds present before photocoagulation largely disappeared afterwards.

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or may never completely absorb. Only two of 20 untreated eyes, originally unclassifiable because of severe vitreal hemorrhage, cleared sufficiently for later classification. Davis15 has also commented on the long per­ sistence of large vitreal hemorrhages. In our experience, proliferative diabetic retinopathy is usually an asymmetrical dis­

AUGUST, 1971

ease. Only a relatively small number of our patients were considered to have symmet­ rical proliferative retinopathy when compar­ ing initial classification data. Therefore, pa­ tients are often seen with far-advanced dis­ ease in one eye and relatively early prolifera­ tive retinopathy in the second eye. The justi­ fication for treating the second eye is based

Fig. 9 (Krill, Archer, Newell, Chishti). Right and left posterior fundi of 66-year-old man (Case 12). Top: Treated right eye (A) two weeks after photocoagulation, and (B) 15 months after photocoagulation. Bottom: Corresponding photographs of the left, or control eye After 15 months, most waxy exudates have disappeared in the treated eye (B), whereas after this lapse of time, there is an increase in the number of waxy exudates in the untreated eye (C and D). Macular edema almost disappeared in the treated eye.

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on data indicating that once one eye has far- (20/80 or better), six (35%) with blind fel­ advanced disease, the other eye often follows low eyes eventually had visual acuity of 20/ 200 or worse in their treated eye during fol­ the same course.16 Several other factors favor treatment of low-up periods which averaged 24 months. In 16 certain eyes with early proliferative retinop- the study cited, where no treatment was given, 59% of the good eyes became blind athy ( P R ) : within one year. 1. Several long-term studies indicate that 15,17 20 eyes with P R do not do well. " Approxi­ 2. Deckert, Simonsen, and Poulsen18 mately 50 to 60% of the eyes with early PR noted that 46% (12* out of 26 patients) of are blind (20/200 vision or worse) within eyes with pre- and peripapillary prolifera­ five years and few retain normal vision. tion went blind (20/200 vision or less) 2. In general, eyes with PR near the disk within two years of follow-up. Twentydo worse than those with PR elsewhere.18 seven percent (7 out of 25 patients) of the Fifty percent of eyes with PR near the disk eyes we treated in this category went blind are blind in two to three years, whereas 50% upon follow-up (a period averaging close to of the eyes with P R elsewhere are blind in two years). five years. At sites distant from the disk, 3. Beetham17 reported data from two-year surface vessels occasionally show spontane­ and longer follow-up periods in eyes with ous regression. initial vision of 20/40 or better in patients 3. The older the patient is, the worse his over 20 years of age. The exact number of prognosis with either proliferative,16,18"22 or eyes could not be calculated from the data given in the paper. After two years, 20% of nonproliferative retinopathy.19'23'24 4. Visual prognosis after a vitreous hem­ the eyes had less than 20/200 vision, and in orrhage is particularly dismal. Even after another 20% vision was between 20/50 and the first vitreous hemorrhage, one-third of 20/200. Of our 20 eyes in this category, five such eyes are permanently blind within one (25%) had worse than 20/200 vision and year and another one-third have permanently four (20%) had vision between 20/50 to 20 /200. However, the average age of our impaired vision.19 It seems, then, that eyes with PR most group (46 of our 56 patients were 45 years likely to benefit from treatment are: (1) or older) may have been considerably those from older patients (beyond the age of higher. (We could not determine how many 40), (2) those with vessels near the optic of Beetham's patients were in this age disk, (3) those with a past or present vitre­ range.) It has been shown that in eyes with ous hemorrhage, or (4) the fellow eye of pa­ PR the long-term visual prognosis is consid­ tients with a severe vitreous hemorrhage or erably worse in those who are 40 years of age or older than it is for a younger age far-advanced PR in the other eye. 17 19 21 group. " - Furthermore, valid compari­ The average follow-up in our series of 56 sons between eyes should probably include patients is only two years; however, some classification as well as visual acuity data. It published data on the natural course in eyes is of interest that in several other series of with PR which can be used for comparative photocoagulated eyes where vision initially purposes are: 16 was 20/40 or better, one-year follow-up 1. In one study it was shown that pa­ studies revealed 53 to 76% of the treated eyes tients severely blind in one eye (20/200 or worse vision) frequently become blind in the remaining good eye (defined as 20/80 or bet­ * Figure 3 of the original publication indicates ter initial vision in this study) in a relatively that three eyes were blind when originally seen and short period of time. Among 17 of our pa­ therefore these were eliminated from this calcula­ tients whose treated eyes had good vision tion.

kept this vision.25 In our series 53% main­ tained 20/40 vision or better. The claim that only five-year data are valid in evaluating treatment25 is questiona­ ble when referring to eyes with PR. This is true particularly where the second eye is al­ ready severely blind,16 of eyes with vitreous hemorrhage,19 and of eyes with proliferative retinopathy near the disk,18 as it has been pointed out that blindness occurs in many of these eyes within one or two years after ini­ tial evaluation. Most important in this type of study was the comparison of both visual acuity and classification data from treated and un­ treated eyes on follow-up. Such evaluation indicated that 31 eyes definitely benefited from photocoagulation. In seven patients, both the treated and untreated eyes did well; therefore, it is uncertain that treatment was of any value in these patients. It is difficult to compare our data with that of other work­ ers, since there are few series in which one eye alone was treated. Okun 26 published data

> ///// Fig. 10 (Krill, Archer, Newell, Chishti). Fluorescein angiograms of the left posterior eyegrounds of a 28-year-old diabetic woman. The angiograms were taken during the midretinal venous phase in all photographs: (A) before photocoagulation, (B) three months afterwards, and (C) six months after­ wards. Note the dilated and irregular capillaries in the macula and surrounding areas before photo­ coagulation. Typical dilated hairpin-like shunt ves­ sels (arrow points to one) are frequently associ­ ated with areas of nonperfused retina. The major retinal veins and arteries are dilated and many microaneurysms are evident. Three months after photocoagulation (B), the retinal capillary archi­ tecture is more regular. The capillaries, shunt ves­ sels, and microaneurysms are all reduced in size, although there is no obvious change in the number of microaneurysms present. The hairpin-like capil­ lary dilations are less obvious (compare arrows in Figs. A and B). Six months after photocoagula­ tion (C), the capillary architecture is again indis­ tinct and microaneurysms are again prominent. Dye leakage is again seen (even more than before pho­ tocoagulation) from several dilated capillaries and microaneurysms, particularly near sites of photo­ coagulation (see arrow at bottom of Fig. C).

from 50 patients where one eye only was treated. In 25 patients, there was no change of status in either eye. In the other 25 pa­ tients, progression occurred in 23 untreated and two treated eyes. In contrast to our experience with PR, pa­ tients with no or minimal P R and bilateral macular edema often had symmetrical in­ volvement. At first, visual results were poor in many patients with bilateral macular edema. However, the visual results improved when we photocoagulated inside the macular branches of the temporal vessels and tempo­ ral to the macula, in addition to the routine sites. All patients treated in this latter man­ ner have shown at least partial absorption of macular edema, although vision has not im­ proved in some because of permanent damage to the fovea, particularly as a consequence of cystoid degeneration. We particularly favor treatment of older diabetic patients with chronic bilateral macu­ lar edema, since spontaneous resolution is unlikely after the age of 40.19>23>27 In gen­ eral, we follow patients with macular edema until progressive visual loss can be adequate­ ly documented, or where, in eyes with vision of 20/60 or worse, we establish that there are no signs of improvement within two to four months. It should be emphasized that the longer macular edema persists, the greater the likelihood of permanent macular damage. We have only treated diabetics with nonproliferative (simple or background) reti-

Fig. 11 (Krill, Archer, Newell, Chishti). Same eye as shown in Figure 10. All photographs were taken three minutes after dye injection: (A) be­ fore photocoagulation, (B) three months after­ ward, and (C) six months afterward. There was considerable decrease in dye leakage throughout the macular area three months after photocoagula­ tion (B), with better visualization of small vessel architecture. Six months after treatment (C), ves­ sel details are again blurred with considerable dye leakage evident, particularly adjacent to sites of photocoagulation.

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B Fig. 12 (Krill, Archer, Newell, Chishti). Photo­ graph at site of pre-retinal hemorrhage in 48-yearold man (A) before photocoagulation and (B) 24 hours later. A considerable portion of the hemor­ rhage has disappeared after direct photocoagula­ tion.

nopathy for chronic macular edema. Because of the favorable natural course in many of these patients,19'23'27"30 it is questionable whether such eyes should be photocoagulated. In fact, in one study 6 1 % of eyes with nonproliferative retinopathy were un­ changed visually after 10 years.28 Visual prognosis is worse in eyes with hemorrhages and exudates than in eyes with only micro-

AUGUST, 1971

aneurysms.28 Also, as indicated previously, the prognosis is worse with age. On the other hand, some eyes with simple diabetic retinopathy progress to proliferative diabetic retinopathy.15-30 At present, it is un­ certain which eyes are likely to show such progression. Furthermore, some workers31"33 feel that there is a predisposition toward ei­ ther proliferative or nonproliferative reti­ nopathy and that these are separate entities. Data which may support this latter notion are the findings that glaucoma and a positive response to topical corticosteroids are more common in patients with nonproliferative retinopathy than in the normal population, but in patients with PR there is the same in­ cidence as in the normal population.34 Probably the two most important benefi­ cial effects of photocoagulation are the elimi­ nation of neovascularization on the retinal surface and a decrease in permeability of small intraretinal vessels. Neovascularization on the retinal surface or extending only slightly into the vitreous is usually eliminated by direct photocoagulation of such areas, or at times, of adjacent retina. New vessels extending more into the vitre­ ous cannot be directly treated with the xenon instrument, but these vessels may decrease in number or even disappear when photocoagu­ lation is placed around the base of such areas. New vessels on the optic disk surface or elsewhere may atrophy even when treat­ ment is quite distant. However, this does not occur with extensive proliferation extending significantly into the vitreous. Photocoagu­ lation in such instances may be placed around the base of such areas, as pointed out, or adjacent to the optic disk if this site is involved. A pronounced decrease in permeability of smaller intraretinal vessels, best demon­ strated by fluorescein angiography, occurs after photocoagulation. Leakage of fluores­ cein from abnormally dilated capillaries and shunt vessels in both directly treated and ad­ jacent retinal areas was sometimes consider­ ably reduced by photocoagulation. This is true even if these vessels persist after treat-

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ment. Persistent vessels are usually reduced in caliber. Decrease in leakage from intraretinal ves­ sels in the macula and reduction in their cali­ ber is most likely secondary to the dimin­ ished blood supply requirement of and re­ duced venous return from destroyed retina. A decrease in the pressure head of venous return ultimately should cause a reduction in the size, and probably the permeability, of small vessel radicles. Possibly, the destruc­ tion of hypoxic areas may also have reduced the production of or eliminated tissue metab­ olites with local toxic effects (such as in­ creased permeability and dilation) upon the retinal vasculature. Wide ranging changes after extensive photocoagulation were demonstrated. These general effects included disappearance of surface retinal vessels at sites distant from photocoagulation, such as on the optic disk surface, reduction in caliber of large retinal veins and arterioles, and frequently mild op­ tic atrophy concomitant with arteriolar at­ tenuation. The changes in the large retinal vessels, like those in the small retinal vessels, may also be secondary to some extent to di­ minished blood supply required and reduced venous return from destroyed retina. How­ ever, this reasoning does not explain attenu­ ation of larger retinal vessels, which may oc­ cur in untreated as well as treated retinal quadrants. It is obvious that it is not neces­ sary to photocoagulate along retinal arteri­ oles, as previously claimed, to produce arte­ riolar attenuation and optic atrophy in pa­ tients with diabetic retinopathy. The atrophy of surface retinal vessels at sites a considerable distance from photocoag­ ulation, such as on the surface of the optic disk, may be due to the elimination of an ab­ normal chemical factor speculated to origi­ nate in hypoxic tissue, which is converted to anoxic tissue. The possibility of a vasoformative factor originating in hypoxic tissues has been previously suggested.35"37 The dis­ appearance of new vessels after treatment suggests that such a factor may aid in main­ taining new vessels as well as stimulating

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their original formation. Strong support for the existence of a chemical factor in hypoxic tissues comes from the notation of the disap­ pearance of new vessels on the surface of the iris after photocoagulation in one patient with diabetic retinopathy and in another with a branch vein occlusion.4 The beneficial effect of reducing the amount of retinal tissue to supply with a presumably limited circulation is also sug­ gested by observations that diabetic retinop­ athy is less frequent or less severe in pa­ tients with a reduction in actively metaboliz­ ing retinal parenchyma. For example, it is known that severe PR is rare in eyes with myopia over five diopters, in eyes with ad­ vanced glaucoma, in eyes with severe chorioretinitic atrophy, or in eyes with a retinal degeneration.28'34-38'39 Photocoagulation is probably contraindicated in patients with advanced PR where there is significant vitreoretinal traction, since the procedure may hasten progression of the disease. Furthermore, on the basis of our limited experience, less photocoagulation should be used in the treatment of aphakic patients with diabetic retinopathy, since it appears that vitreous retraction in the macular area is more likely to occur in such pa­ tients. In general, our best results were obtained with extensive photocoagulation. Direct treatment of only proliferative areas was not enough. In such cases, new surface retinal vessels continued to form and generalized effects were lesser in degree, or not noted. It is recommended that photocoagulation should destroy not only obvious proliferative sites, but in addition, destroy retina consid­ ered unimportant for visual purposes. The beneficial effects of such treatment were demonstrated in this report. The results of inadequate treatment in patients with chronic macular edema was also discussed. Careful follow-up of treated patients with diabetic retinopathy is important for several reasons. First of all, the full effect of exten­ sive photocoagulation may not be noted for up to four months after treatment. Secondly,

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certain changes may necessitate retreatment. Fresh areas of retinitis proliferans and sur­ face neovascularization may occur adjacent to areas of photocoagulation, probably as the result of venous obstruction, stasis, and hypoxia with renewed stimulus to new vessel growth. This finding was most frequent where a photocoagulation scar occurred di­ rectly over or adjacent to a large retinal vein, compromising blood flow in the vessel. Fi­ nally, some patients with previously resolved macular edema may again start to leak from dilated capillaries and shunts in the macula within six to 12 months after initial treat­ ment. Retreatment may be beneficial in such patients. Also, on occasion, dilated capillaries and shunts which had atrophied reappeared in such patients. It appears on the basis of our experience to date, that "permanent" remissions occur more commonly in patients in whom PR is the sole reason for treatment. Such patients may be hastened into the final atrophic stage by photocoagulation, supposedly the end stage of many untreated eyes with PR. 40 On the other hand, the problem of permanently diseased, leaky, small intraretinal vessels in the macular area of treated patients with macular edema remains, and possibly such patients will never have a permanent "cure" after photocoagulation. The most frequent cause of a poor result in patients with early PR was the eventual development of an extensive proliferative growth on the optic disk surface. Perhaps extensive photocoagulation, including treat­ ment adjacent to the nasal half of the disk, prevents this occurrence. Only a few pa­ tients treated in this manner have developed significant proliferation on the disk surface. Therefore, we now routinely photocoagulate patients with PR nasal to the optic disk. Hopefully, the argon laser, which photocoagulates vessels that are not in contact with the retinal surface, can be used to treat many of the eyes with extensive vasculature a suf­ ficient distance above the retina that have not responded to photocoagulation. Preliminary data in this area are encouraging.41

AUGUST, 1971

SUMMARY

Data are presented from 56 patients with diabetic retinopathy who were followed for one year or more after photocoagulation of one eye only. On the basis of visual acuity and changes in classification in the treated eye, 31 of these patients had some benefit from photocoagulation. Fifteen patients did poorly. Ten of these had advanced prolifera­ tive retinopathy. Four were thought to have had inadequate photocoagulation. (The ne­ cessity for extensive photocoagulation in most patients is stressed.) One patient had insufficient follow-up, and the importance of adequate follow-up is emphasized, particu­ larly in patients with macular edema. Ten patients had inconclusive results. In seven of these, both treated and untreated eyes did well, and three had deterioration in both eyes. No conclusions regarding the effects of photocoagulation were possible in these patients. Photocoagulation has both local and wide­ spread effects. Probably the two most impor­ tant effects are the elimination of areas of surface proliferation and a general decrease in the permeability of small retinal vessels. The possibility of a chemical factor exist­ ing in hypoxic tissues causing the formation and maintenance of new vessels, even at dis­ tant sites, is suggested. It is speculated that photocoagulation converts hypoxic to anoxic tissue, presumably eliminating such a factor. Photocoagulation, if used properly, is of definite value in certain patients with early and moderately advanced proliferative dia­ betic retinopathy, and in certain patients with chronic macular edema.

ACKNOWLEDGMENT

We acknowledge the valuable assistance of Mrs. Miriam Creeden in the handling of the large body of data accumulated in this study. REFERENCES

1. Archer, D., Krill, A. E , and Newell, F. W.: Fluorescein studies of normal choroidal circulation. Am. J. Ophth. 69:543, 1970.

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