Florid Diabetic Retinopathy and its Response to Treatment by Photocoagulation or Pituitary Ablation Eva M. Kohner, M.D., M.R.C.P., A. M. Hamilton, F.R.C.S., G. F. Joplin, Ph.D., F.R.C.P., and T. R. Fraser, M.D., F.R.C.P., London, England
SUMMARY
A group of 34 patients with florid diabetic retinopathy are reported. Nine of these had at least one eye untreated and of these only two maintained vision at one year—the others were blind. Ten patients had 11 florid eyes treated by photocoagulation. At one year six were blind and five had good vision. At two years only three could still see. Of 20 pituitary-ablated patients with 29 florid eyes, only three were blind at one year. Even at five years,
12 of 17 eyes could see and only two patients were blind. The oneand two-year visual acuities were significantly better in the pituitary-ablated eyes than in the untreated and photocoagulated ones (p = 0.01 - 0.03). It is suggested that for this rare form of retinopathy pituitary ablation remains the treatment of choice if vision is to be maintained. DIABETES 25:104-10, February, 1976.
Florid retinopathy is a rare form of diabetic retinopathy. It usually affects patients under the age of 40 years with long-standing, often poorly controlled diabetes. Its evolution has been described by Beaumont and Hollows 1 as rapid, bloody, and blinding. Between 1965 and 1973, 34 such patients were seen at the Hammersmith Hospital Diabetic Retinopathy Clinic. This paper describes the natural history of the untreated condition and the results with photocoagulation and pituitary ablation.
(figure I) 2 in two or more 30° photographic fields excluding that centered on the disc. In addition, the eye should not have fibrous retinitis proliferans of severity that would make favorable outcome unlikely. Patients All patients who had this severity of retinopathy in one or both eyes and have been followed for at least one year after the diagnosis was made are included in this analysis. Because of the rarity of the condition, this type of retinopathy was not considered suitable for formal clinical trials. The first patient in the series had very poor diabetic control and was advised to improve this prior to considering pituitary ablation. During the next three months, while better control was achieved, he lost his sight. Following this experience and the favorable result with pituitary ablation in the first few patients, this treatment was offered to all between 1965 and 1970. Altogether 20 patients had pituitary ablation. There were 29 florid eyes in this group; eight were too severely affected for treatment to be expected to have an effect, and three patients had milder retinopathy in the second eye. The general criteria for pituitary ablation were a visual acuity of at
DEFINITION, PATIENTS, AND METHODS Definition In order to be considered as having florid retinopathy an eye must have new-vessel formation equal to or worse than Hammersmith Hospital Standard C From the Endocrine Unit, Department of Medicine, Hammersmith Hospital, Royal Postgraduate Medical School, and the Retinal Diagnostic Department, Moorfields Eye Hospital, London, England. Address reprint requests to E.M. Kohner, Hammersmith Hospital, Du Cane Road, London, W12 OHS, England. Accepted for publication November 24, 1975. 104
DIABETES, VOL. 2 5 , NO. 2
EVA M. KOHNER, M.D., M.R.C.P., AND ASSOCIATES
photocoagulation (see above). The last patient with an untreated florid eye had severe but not florid retinopathy in his second eye, which was photocoagulated. Since 1973, patients who had pituitary ablation have at three months one of the two eyes treated by photocoagulation if this is still indicated (i.e. there are still treatable new vessels present). There are two patients who had both procedures. Details of the patients are shown in table 1. These show that the mean age of the photocoagulation group was significantly greater than the other two groups, because of one patient who was 50 years old at the time of entry. The duration of diabetes, plasma urea, and initial visual acuity were similar in the three groups. Methods
FIG. 1. Hammersmith Hospital Standard C for new vessels. Approximately half of the 30° field is covered by new vessels.
least 6/24 in the better eye, plasma urea below 75 mg./lOO ml., and absence of symptomatic postural hypotension. The patient had to be judged capable of managing the hypopituitary state. After 1970, photocoagulation became available and the next 10 patients were offered this form of treatment. Five with two florid eyes had one, chosen by a random procedure, treated; the other eye was left untreated. One with two florid eyes had both treated. The remaining four patients had only one seeing eye, so only this (florid) eye was treated. There were therefore 11 eyes treated by photocoagulation. There were nine patients with 11 untreated florid eyes. Three patients were considered unsuitable for pituitary ablation on general grounds or declined operation when this was offered. Two had two florid eyes; one had only one (the other eye having milder retinopathy). Five had the second eye treated by
Initially photocoagulation was performed solely with the xenon-arc photocoagulator, but after 197 1 the Coherent Radiation Model 800 argon laser became available, and in six patients this has been used when indicated for forward retinal and disc vessels. Both peripheral ablation of an abnormal and possibly ischemic retina and treatment of all visible lesions were attempted where possible. Adequate peripheral ablation was achieved in all but one patient. In this patient the total number of xenon coagulation burns was less than 500; she did not return for further therapy after losing vision in both the treated and untreated eye shortly after the first treatment session. Pituitary ablation was performed by yttrium-90 implantation 3 giving 150,000 rads (1965-1968) and 300,000 rads (after 1968) at the gland periphery and aiming at maximal ablation of pituitary function. This aim was achieved by one operation in six patients (four had 150,000 rads and two 300,000 rads). In five further patients a second dose resulted in maximal ablation, but in four patients even with two doses this aim was not achieved. In five patients only partial ablation was achieved but a second operation was not performed, in three because the results were satisfac-
TABLE 1
Group Untreated Photocoagulated Pituitary-ablated
No. of patients 9 10 20
No. of florid eyes 11 11 29
Age mean (range) (years) 28.2 (23-35) 33.3 (23-50)* 25.5 (19-37)
Duration of D.M. mean (range) (years) 17.3 (7-24) 15.7 (1-24) 17.5 (1-29)
Plasma urea mean (range) mg./lOO ml. 30.0 (26-53) 40.7 (23-53) 36.1 (24-55)
Visual acuityt mean ± S.E. 2.5 ± 0.33 3.0 ± 0.6 3.1 ± 1.0
•Significant difference from other groups (p < 0.01). tVisual acuity scale as described in text (6/6 = 1,6/9 = 2, 6/12 = 3, etc). FEBRUARY, 1976
105
FLORID DIABETIC RETINOPATHY AND ITS RESPONSE TO TREATMENT
tory and in two because the eye for which the operation was initially performed became blind in the intervening period. The criteria for maximal ablation were both clinical and laboratory evidence of thyroid and steroid deficiency, 45 drop of insulin requirement by at least 45 per cent, and absent or near-absent growthhormone response to insulin-induced hypoglycemia.6 Thyroid-stimulating hormone (TSH), luteinizing hormone (LH), and follicle-stimulating hormone (FSH) were measured in more recent patients as these measurements became available. For these, low basal levels with no rise after releasing hormone (200 /xg. TRH or 100 /xg. LRH) was considered essential for maximal ablation. Patients were considered to have "partial" ablation if some but not all these hormones were affected. In patients graded as having "slight" ablation, no obvious pituitary deficiency was noted (though usually there was a small drop in insulin requirement). There were three such patients among those who did not have a second operation. All patients were seen regularly, at least every three months in the first year and every six months thereafter, unless they were abroad or blind. In addition, all photocoagulated patients were seen three weeks after the first and any major treatment. Analysis of Visual Acuity To enable statistical analysis, the visual acuity was converted into numerical grades, 616 = 1, 6/9 — 2, etc., to no perception of light = 12, as described previously.7 For analysis, the best corrected visual acuity taken at the yearly visit was compared with the initial visual acuity (or pretreatment visual acuity) in each group by the Student's t test for paired samples. The treated and untreated eyes were compared with each other initially and yearly by the Student's / test for unpaired samples. Corrections for small numbers were made where necessary. Eyes with visual acuity of 6/60 or less on the Snellen chart were considered blind. RESULTS
PL
•
•
y'
HM
«
3/60
1 6/60 S
6/36
-
6/24
•
y'
6/18 6/12
6/9
>/
*
i
i
6/6 /
i
i
i
i
i
i
i
i
i
j
6/6 6/9 6/12 6/18 6/24 6/36 6/60 3/60 CF HM PL NPL Initial visual acuity FIG. 2.
Comparison of initial and one-year visual acuity in untreated florid eyes. Solid line indicates "no change." Those to the right of this line improved; those to the left deteriorated. CF = counting fingers, HM = hand movement, PL = perception of light, NPL = no perception of light.
then had a pituitary ablation (which he previously refused); the other has now been followed for four years and still maintains normal vision (6/9), though he had his first two vitreous hemorrhages during the last year. The mean visual acuity in this group of NPL PL HM
1 6/60 S 6/36 - 6/24 6/18 6/12 6/9
Visual Acuity Untreated group. The initial visual acuity in this group was similar to the photocoagulated and pituitary-ablated group (table 1). By one year only two eyes retained normal vision, and the remaining nine were blind (figure 2). Of the two patients retaining good vision, one became blind in his other eye and 106
6/6 6/6 6/9 6/12 6/18 6/24 6/36 6/60 3/60 CF HM PL NPL Initial visual acuity FIG. 3.
Comparison of initial and one-year visual acuity in photocoagulated florid eyes. Annotation same as figure 2. DIABETES, VOL. 2 5 , NO. 2
EVA M. KOHNER, M.D., M.R.C.P., AND ASSOCIATES
NPL
seven eyes followed could still see (figure 4), but all had recurrent vitreous hemorrhages. These three eyes could still see at three years. Only two eyes have been followed for more than three years; one maintains vision at 6/18, the other is blind. Pituitary-ablated group. Twenty-five of the 29 eyes (in 20 patients) had an initial visual acuity of 6/18 or better. At one year 19 still retained this degree of visual acuity (figure 5), of whom six eyes improved their visual acuity by two lines or more; only three eyes were blind. Among the 17 eyes followed for five years, 10 maintained a visual acuity of 6/18 or better (figure 6). Even after this long period of follow-up there were only five blind eyes and two blind patients. At both one and two years the mean visual acuity in the group treated by pituitary ablation was signifi6/6 6/9 6/12 6/18 6/24 6/36 6/60 3/60 CF HM PL NPL cantly better than in the untreated (p
SUMMARY
A group of 34 patients with florid diabetic retinopathy are reported. Nine of these had at least one eye untreated and of these only two maintained vision at one year—the others were blind. Ten patients had 11 florid eyes treated by photocoagulation. At one year six were blind and five had good vision. At two years only three could still see. Of 20 pituitary-ablated patients with 29 florid eyes, only three were blind at one year. Even at five years,
12 of 17 eyes could see and only two patients were blind. The oneand two-year visual acuities were significantly better in the pituitary-ablated eyes than in the untreated and photocoagulated ones (p = 0.01 - 0.03). It is suggested that for this rare form of retinopathy pituitary ablation remains the treatment of choice if vision is to be maintained. DIABETES 25:104-10, February, 1976.
Florid retinopathy is a rare form of diabetic retinopathy. It usually affects patients under the age of 40 years with long-standing, often poorly controlled diabetes. Its evolution has been described by Beaumont and Hollows 1 as rapid, bloody, and blinding. Between 1965 and 1973, 34 such patients were seen at the Hammersmith Hospital Diabetic Retinopathy Clinic. This paper describes the natural history of the untreated condition and the results with photocoagulation and pituitary ablation.
(figure I) 2 in two or more 30° photographic fields excluding that centered on the disc. In addition, the eye should not have fibrous retinitis proliferans of severity that would make favorable outcome unlikely. Patients All patients who had this severity of retinopathy in one or both eyes and have been followed for at least one year after the diagnosis was made are included in this analysis. Because of the rarity of the condition, this type of retinopathy was not considered suitable for formal clinical trials. The first patient in the series had very poor diabetic control and was advised to improve this prior to considering pituitary ablation. During the next three months, while better control was achieved, he lost his sight. Following this experience and the favorable result with pituitary ablation in the first few patients, this treatment was offered to all between 1965 and 1970. Altogether 20 patients had pituitary ablation. There were 29 florid eyes in this group; eight were too severely affected for treatment to be expected to have an effect, and three patients had milder retinopathy in the second eye. The general criteria for pituitary ablation were a visual acuity of at
DEFINITION, PATIENTS, AND METHODS Definition In order to be considered as having florid retinopathy an eye must have new-vessel formation equal to or worse than Hammersmith Hospital Standard C From the Endocrine Unit, Department of Medicine, Hammersmith Hospital, Royal Postgraduate Medical School, and the Retinal Diagnostic Department, Moorfields Eye Hospital, London, England. Address reprint requests to E.M. Kohner, Hammersmith Hospital, Du Cane Road, London, W12 OHS, England. Accepted for publication November 24, 1975. 104
DIABETES, VOL. 2 5 , NO. 2
EVA M. KOHNER, M.D., M.R.C.P., AND ASSOCIATES
photocoagulation (see above). The last patient with an untreated florid eye had severe but not florid retinopathy in his second eye, which was photocoagulated. Since 1973, patients who had pituitary ablation have at three months one of the two eyes treated by photocoagulation if this is still indicated (i.e. there are still treatable new vessels present). There are two patients who had both procedures. Details of the patients are shown in table 1. These show that the mean age of the photocoagulation group was significantly greater than the other two groups, because of one patient who was 50 years old at the time of entry. The duration of diabetes, plasma urea, and initial visual acuity were similar in the three groups. Methods
FIG. 1. Hammersmith Hospital Standard C for new vessels. Approximately half of the 30° field is covered by new vessels.
least 6/24 in the better eye, plasma urea below 75 mg./lOO ml., and absence of symptomatic postural hypotension. The patient had to be judged capable of managing the hypopituitary state. After 1970, photocoagulation became available and the next 10 patients were offered this form of treatment. Five with two florid eyes had one, chosen by a random procedure, treated; the other eye was left untreated. One with two florid eyes had both treated. The remaining four patients had only one seeing eye, so only this (florid) eye was treated. There were therefore 11 eyes treated by photocoagulation. There were nine patients with 11 untreated florid eyes. Three patients were considered unsuitable for pituitary ablation on general grounds or declined operation when this was offered. Two had two florid eyes; one had only one (the other eye having milder retinopathy). Five had the second eye treated by
Initially photocoagulation was performed solely with the xenon-arc photocoagulator, but after 197 1 the Coherent Radiation Model 800 argon laser became available, and in six patients this has been used when indicated for forward retinal and disc vessels. Both peripheral ablation of an abnormal and possibly ischemic retina and treatment of all visible lesions were attempted where possible. Adequate peripheral ablation was achieved in all but one patient. In this patient the total number of xenon coagulation burns was less than 500; she did not return for further therapy after losing vision in both the treated and untreated eye shortly after the first treatment session. Pituitary ablation was performed by yttrium-90 implantation 3 giving 150,000 rads (1965-1968) and 300,000 rads (after 1968) at the gland periphery and aiming at maximal ablation of pituitary function. This aim was achieved by one operation in six patients (four had 150,000 rads and two 300,000 rads). In five further patients a second dose resulted in maximal ablation, but in four patients even with two doses this aim was not achieved. In five patients only partial ablation was achieved but a second operation was not performed, in three because the results were satisfac-
TABLE 1
Group Untreated Photocoagulated Pituitary-ablated
No. of patients 9 10 20
No. of florid eyes 11 11 29
Age mean (range) (years) 28.2 (23-35) 33.3 (23-50)* 25.5 (19-37)
Duration of D.M. mean (range) (years) 17.3 (7-24) 15.7 (1-24) 17.5 (1-29)
Plasma urea mean (range) mg./lOO ml. 30.0 (26-53) 40.7 (23-53) 36.1 (24-55)
Visual acuityt mean ± S.E. 2.5 ± 0.33 3.0 ± 0.6 3.1 ± 1.0
•Significant difference from other groups (p < 0.01). tVisual acuity scale as described in text (6/6 = 1,6/9 = 2, 6/12 = 3, etc). FEBRUARY, 1976
105
FLORID DIABETIC RETINOPATHY AND ITS RESPONSE TO TREATMENT
tory and in two because the eye for which the operation was initially performed became blind in the intervening period. The criteria for maximal ablation were both clinical and laboratory evidence of thyroid and steroid deficiency, 45 drop of insulin requirement by at least 45 per cent, and absent or near-absent growthhormone response to insulin-induced hypoglycemia.6 Thyroid-stimulating hormone (TSH), luteinizing hormone (LH), and follicle-stimulating hormone (FSH) were measured in more recent patients as these measurements became available. For these, low basal levels with no rise after releasing hormone (200 /xg. TRH or 100 /xg. LRH) was considered essential for maximal ablation. Patients were considered to have "partial" ablation if some but not all these hormones were affected. In patients graded as having "slight" ablation, no obvious pituitary deficiency was noted (though usually there was a small drop in insulin requirement). There were three such patients among those who did not have a second operation. All patients were seen regularly, at least every three months in the first year and every six months thereafter, unless they were abroad or blind. In addition, all photocoagulated patients were seen three weeks after the first and any major treatment. Analysis of Visual Acuity To enable statistical analysis, the visual acuity was converted into numerical grades, 616 = 1, 6/9 — 2, etc., to no perception of light = 12, as described previously.7 For analysis, the best corrected visual acuity taken at the yearly visit was compared with the initial visual acuity (or pretreatment visual acuity) in each group by the Student's t test for paired samples. The treated and untreated eyes were compared with each other initially and yearly by the Student's / test for unpaired samples. Corrections for small numbers were made where necessary. Eyes with visual acuity of 6/60 or less on the Snellen chart were considered blind. RESULTS
PL
•
•
y'
HM
«
3/60
1 6/60 S
6/36
-
6/24
•
y'
6/18 6/12
6/9
>/
*
i
i
6/6 /
i
i
i
i
i
i
i
i
i
j
6/6 6/9 6/12 6/18 6/24 6/36 6/60 3/60 CF HM PL NPL Initial visual acuity FIG. 2.
Comparison of initial and one-year visual acuity in untreated florid eyes. Solid line indicates "no change." Those to the right of this line improved; those to the left deteriorated. CF = counting fingers, HM = hand movement, PL = perception of light, NPL = no perception of light.
then had a pituitary ablation (which he previously refused); the other has now been followed for four years and still maintains normal vision (6/9), though he had his first two vitreous hemorrhages during the last year. The mean visual acuity in this group of NPL PL HM
1 6/60 S 6/36 - 6/24 6/18 6/12 6/9
Visual Acuity Untreated group. The initial visual acuity in this group was similar to the photocoagulated and pituitary-ablated group (table 1). By one year only two eyes retained normal vision, and the remaining nine were blind (figure 2). Of the two patients retaining good vision, one became blind in his other eye and 106
6/6 6/6 6/9 6/12 6/18 6/24 6/36 6/60 3/60 CF HM PL NPL Initial visual acuity FIG. 3.
Comparison of initial and one-year visual acuity in photocoagulated florid eyes. Annotation same as figure 2. DIABETES, VOL. 2 5 , NO. 2
EVA M. KOHNER, M.D., M.R.C.P., AND ASSOCIATES
NPL
seven eyes followed could still see (figure 4), but all had recurrent vitreous hemorrhages. These three eyes could still see at three years. Only two eyes have been followed for more than three years; one maintains vision at 6/18, the other is blind. Pituitary-ablated group. Twenty-five of the 29 eyes (in 20 patients) had an initial visual acuity of 6/18 or better. At one year 19 still retained this degree of visual acuity (figure 5), of whom six eyes improved their visual acuity by two lines or more; only three eyes were blind. Among the 17 eyes followed for five years, 10 maintained a visual acuity of 6/18 or better (figure 6). Even after this long period of follow-up there were only five blind eyes and two blind patients. At both one and two years the mean visual acuity in the group treated by pituitary ablation was signifi6/6 6/9 6/12 6/18 6/24 6/36 6/60 3/60 CF HM PL NPL cantly better than in the untreated (p
