RUBEOSIS IRIDIS AND NEOVASCULAR GLAUCOMA

Neovascular glaucoma, secondary to ru-beosis iridis, is one of the most difficult types of glaucoma to manage. Intraocular pressure control and retention of useful vision are rare, and a substantial number of such eyes are eventually enucleated. Usually, medical therapy controls neither the pressure nor the pain, and conventional filtering procedures are useless or disastrous. Although cyclo-diathermy showed promise of salvaging some of these eyes, reports are thus far inconclu­sive.1»2

Since the introduction of cryosurgery of the ciliary body for glaucoma in 1950, exten­sive work has been done with this procedure, both experimentally and clinically.3 In gen­eral, cryosurgical results in the secondary glaucomas have been disappointing.4"9 For example, DeRoetth4 achieved pressure con­trol in only 20% of his cases of secondary glaucoma. Only one report, utilizing a se­quential application of cryotherapy, indicated promising results in the treatment of secon­dary glaucoma.10

However, in previously published series of cyclocryotherapy for secondary glaucomas, there are only a few eyes with neovascular glaucoma; thus, it is impossible to evaluate adequately this mode of therapy in these eyes. In reviewing the use of cyclocryotherapy at this institution over the past seven years, we found a total of 38 eyes with neovascular glau­coma that were treated by this method. These eyes are the basis for the present report.

From the Department of Ophthalmology, Wash­ington University School of Medicine. This study was supported in part by Public Health Service Grants EY-00336 and EY-00016 from the National Eye Institute, Bethesda, Maryland.

Reprint requests to John F. Bigger, M.D., De­partment of Ophthalmology, Washington Univer­sity School of Medicine, 660 South Euclid Avenue, St. Louis, Missouri 63110.

MATERIALS AND METHODS

The surgical records for the years 1964-71 at McMillan Hospital in St. Louis were re­viewed. There were 34 patients with rubeo-sis iridis and neovascular glaucoma for whom adequate clinical information and follow-up could be obtained. Of these, half were males, 25 were white, and nine were black.

In this population, 38 eyes received 52 treatments. In 24 eyes, the rubeosis was as­sociated with diabetes mellitus; in 11 eyes, it was secondary to retinal vascular occlusion. In three eyes, both processes coexisted.

All eyes were followed for at least three months, and the majority were followed for six months or longer (Table 1).

The procedures were performed in the op­erating room under topical and retrobulbar anesthesia. Several different cryotherapy in­struments were employed. Only eyes treated with cryotherapy over the entire 360-degree circumference of the ciliary body were in­cluded in this study. Eyes were treated post-operatively with topical cycloplegics and cor-ticosteroids.

The intraocular pressure response to ther­apy was determined as follows : First, we de­termined the number of eyes in which the pressure reduction was greater than 50% of the pretreatment level. Eyes in which the pressure reduction was 0 to 50% of the pre­treatment level were also tabulated, as were eyes in which the postoperative pressures were increased. Second, we determined the number of eyes in which the final postopera­tive pressure was less than 20 mm Hg. Eyes which were in chronic hypotony (pressure below 10 mm Hg) were also noted. Intraoc­ular pressure response data were based on pressure changes which persisted to the time of the last available follow-up, and transient

EVALUATION OF CYCLOCRYOTHERAPY

ROBERT M. FEIBEL, M.D., AND JOHN F. BIGGER, M.D. Si. Louis, Missouri

VOL. 74, NO. S RUBEOSIS IRIDIS 863

T A B L E 1

DURATION OF FOLLOW-UP OF 38 EYES TREATED WITH CYCLOCRYOTHERAPY

Last Available Follow-up Examination

No. Eyes

Three months Six months 12 months 24 months

S 11 14 8

changes in pressure in the immediate postop­erative period were ignored. Statistical com­parisons were performed by the chi-square contingency method.

RESULTS

The intraocular pressure response at the last available follow-up examination for the 38 eyes is shown in Table 2. A reduction in pressure of greater than 50% of the pre-treatment level was attained in 26 eyes. In 24 eyes the pressure was maintained below 20

mm Hg. No statistical difference in response to cyclocryotherapy was found between white and black patients. A review of the data re­vealed no difference in the number of treat­ments given to either racial group.

The 38 eyes in this series were subdivided into three groups as follows: Group 1 in­cluded 24 eyes treated only once. Group 2 in­cluded seven eyes treated on two occasions several weeks or months apart, the second treatment being done because the first treat­ment was unsuccessful. Group 3 included seven eyes treated twice in a planned sequen­tial manner, with the second treatment following the first by an interval of one to two weeks. In this last group there was an inadequate time interval between treatments to determine the effect on intraocular pres­sure of the first treatment.

Using this classification it was possible to compare the results of the initial versus re­peated cyclocryotherapies. Table 3 compares the pressure response of 31 eyes following

TABLE 2 INTRAOCULAR PRESSURE RESPONSE IN 38 EYES AFTER ONE OR MORE CYCLOCRYOTHERAPY TREATMENTS*

Intraocular Pressure White Patients (26 eyes)

Black Patients (12 eyes)

Total

Decreased > 5 0 % Decreased 0-50% Increased

<20 mm Hg Hypotony

19 (73%) 6 (23%) 1 (04%)

16 (62%) 9 (35%)

7 (58%) 3 (25%) 2 (17%)

8 (67%) 3 (25%)

26 (64%) 9 (24%) 3 (08%)

24 (63%) 12 (32%)

* Differences are not statistically significant between lightly and heavily pigmented eyes.

TABLE 3 INTRAOCULAR PRESSURE RESPONSE TO CYCLOCRYOTHERAPY AFTER SINGLE vs REPEATED TREATMENTS

Intraocular Pressure Single Treatment (31 eyes)

Repeated Treatment (14 eyes)

Decreased > 5 0 % Decreased 0-50% Increased

<20 mm Hg Hypotomy

15 (48%) 11 (36%) 5 (16%)

12 (39%) 8 (26%)

12 (86%) 1 (07%) 1 (07%)

12 (86%) 4 (29%)

( p < 0 . 0 5 )

( p < 0 . 0 1 )

864 AMERICAN JOURNAL OF OPHTHALMOLOGY NOVEMBER, 1972

the initial cryosurgery (including Group 1 and the first treatment in Group 2) with the pressure response of 14 eyes treated twice (final response in Group 2 and Group 3) . A greater than 50% reduction in intraocular pressure was obtained in IS eyes after the initial treatment, and in 12 eyes with re­peated treatments (p < 0.05). In 12 eyes, pressure less than 20 mm Hg was obtained after the initial treatment, and it was main­tained under 20 mm Hg in another 12 eyes after repeated treatments (p < 0.01). There was no greater incidence of induced hypo-tony following the second treatment than af­ter the first procedure.

The effect of the duration of the cryoappli-cation upon the final pressure response is shown in Table 4. Because it was not possi­ble to evaluate duration of freezing where an eye was treated more than once, these data are based only on the initial treatment in 31 eyes. Although the data suggest that eyes in which the duration of freezing was 60 seconds or longer had better pressure control, these dif­ferences were not statistically significant be­cause of small numbers.

In these eyes, the temperature of the cryo-probe was either —60° or —80e C. When the pressure response to the initial cryotherapy in 31 eyes was compared for the two temper­atures, no significant difference was found (Table 5).

Although all eyes were treated circumfer-entially over the entire ciliary body, the tech­nique of cryoapplications varied. Some eyes were treated by a single continuous applica­tion of the cryoprobe ; others were treated by a freeze-thaw-refreeze technique in which the cryoprobe was applied, allowed to freeze, thawed, and then reapplied to the same loca­tion for a further freeze. When the pressure response for the initial treatment in the 31 eyes was compared for these two methods, no statistical difference was found.

Visual acuity prior to treatment and at the last follow-up examination is shown in Table 6. Vision was improved postoperatively in only two eyes, and in the 14 eyes in which vision was counting fingers or better preop­eratively, only six maintained similar acuity following the cryosurgery. Seventeen eyes had no light perception postoperatively, in­cluding three eyes without light perception before surgery, but also including four in which vision was counting fingers or better preoperatively. At the last follow-up, only six eyes had retained vision of counting fin­gers or better.

Many eyes showed an initial rise in pres­sure several hours after surgery, persisting for various periods of time.

Following cryotherapy, all eyes demon­strated a moderate to severe iridocyclitis re­quiring topical corticosteroids and cyclo-

TABLE 4 EFFECT OF DURATION OF CRYOAPPLICATION ON INTRAOCULAR PRESSURE IN 31 EYES

AFTER SINGLE APPLICATION OF CYCLOCRYOTHERAPY*

Intraocular Pressure

Decreased >50% Decreased 0-50% Increased

<20 mm Hg Hypotony

<30 Seconds (10 eyes)

4 (40%) 4 (40%) 2 (20%)

3 (30%) 2 (20%)

Duration of Application

30-60 Seconds (9 eyes)

3 (33%) 5 (56%) 1 (H%)

3 (33%) 2 (22%)

>60 Seconds (12 eyes)

8 (67%) 2 (16%) 2 (16%)

6 (50%) 4 (33%)

* Differences are not statistically significant.

VOL. 74, NO. 5 RUBEOSIS IRIDIS 865

TABLE 5 EFFECT OF CRYOPROBE TEMPERATURE ON INTRAOCULAR PRESSURE IN 31 EYES

AFTER SINGLE APPLICATION OF CRYOTHERAPY*

Temperature Intraocular Pressure

Decreased >50% Decreased 0-50% Increased

<20 mm Hg Hypotony

-60° C (.15 eyes)

7 (47%) 6(40%) 2 (13%)

6 (40%) 3 (20%)

-80° C (16 eyes)

8 (50%) 5 (31%) 3 (19%)

6 (38%) 5 (31%)

* Differences are not statistically significant.

plegic medication; in a few cases systemic corticosteroids were used. Many eyes showed extensive posterior synechiae and pig­ment dispersion. Often there was a postoper­ative hyphema which, in a few eyes, per­sisted for several weeks, but in no eye was a severe intraocular hemorrhage noted.

A dense cataract developed after the pro­cedure in 10 eyes in this series.

Twelve eyes developed chronic hypotony. The frequency of secondary hypotony did not increase with repeated treatments (Table 3) . It occurred with equal incidence follow­ing the different durations and temperatures employed in this study (Tables 4 and 5). All such eyes had vision of hand motion or less postoperatively. In 10 of the 12 eyes, the hy­potony developed within three months after surgery and persisted. In two eyes, the hypo­tony developed two or more years after treatment, with no subsequent surgery per­formed. Three eyes were eventually enucle­ated.

In the majority of cases, cyclocryotherapy controlled the pain of the acute congestive glaucoma, and the eyes were often comfort­able even if the pressure remained elevated.

DISCUSSION

This study shows that cyclocryotherapy is a useful method of reducing the intraocular pressure in eyes with neovascular glaucoma.

With one or more treatments a reduction in pressure of greater than 50% of the preop-erative level was achieved in 26 of 38 eyes. A pressure below 20 mm Hg was maintained in 24 eyes (Table 2) .

Although there is both experimental and clinical11 evidence that better pressure con­trol can be obtained in more heavily pig-mented eyes, we found no difference in re­sponse to therapy in black patients. In a study of eyes with advanced chronic simple glaucoma, DeRoetth11 obtained significantly better pressure control in the eyes of black patients after repeated cryotreatments, but he also noted a higher incidence of serious complications in darkly pigmented eyes.

A striking feature of this study was the excellent pressure control achieved in eyes

TABLE 6 VISUAL ACUITY OF 38 EYES BEFORE

AND AFTER CYCLOCRYOTHERAPY

Visual Acuity

20/20-20/100 20/200-20/400 Counting fingers Hand motion to light

perception No light perception

No. Eyes

Preoperative Postoperative

3 0 2 2 9 4

21 15 3 17

866 AMERICAN JOURNAL OF OPHTHALMOLOGY NOVEMBER, 1972

treated on two occasions. In 12 of these eyes pressure reduction was greater than 50% of the pretreatment level and it was main­tained below 20 mm Hg. These results were significantly better than those obtained after only one treatment (Table 3) . DeRoetth11

noted a similar finding in his series of eyes with open-angle glaucoma. Chenoweth10 also reported excellent results in a small series of secondary glaucomas treated in a planned se­quential manner. Further, our study demon­strated that there was no greater incidence of induced chronic hypotony following the second treatment compared to that following the first. One is thus encouraged to repeat the operation if the initial cryotherapy is not successful.

By evaluating the results of the initial cy-clocryotherapies alone, several conclusions about the dose-response curve of cryotreat-ment were noted. First, although there was better pressure control in eyes treated with longer periods of cryoapplication, these dif­ferences were not significant on a statistical analysis (Table 4) . Second, the temperature of the cryoprobe did not affect the results, within the range used in these patients (Ta­ble 5). This may reflect, in part, the differ­ence between the temperature of the cryo-surgical probe and the temperature attained in the ciliary body, as determined in the rab­bit by DeRoetth.12 It may also reflect differ­ences in the various cryotherapy instruments used in this study. Finally, although several investigators13'14 report increased cellular destruction when two or more freeze-thaw cycles are used, this was not confirmed in our study. There was no difference in re­sponse to therapy in eyes receiving a single continuous treatment and eyes receiving a freeze-thaw-re freeze method of treatment.

When the results of this study were com­pared to those of other glaucoma procedures, the results of cyclocryotherapy were better. In a retrospective study of eyes with "hemor-rhagic" glaucoma treated by various proce­dures, Müller-Jensen15 reported that only

two of 41 eyes treated with Preziosi's oper­ation had adequate pressure control one year after surgery. In 18 eyes in which a cyclo-diathermy was performed, only one had pressure control one year after the proce­dure.

The presence of advanced proliferative di­abetic retinopathy or retinal vascular occlu­sive disease adversely affects the visual po­tential. Other factors which might influence the visual results were the development of cataracts and the marked rise in intraocular pressure in the immediate postoperative pe­riod.

While the incidence of complications was high, in view of the dismal prognosis for such eyes, the rate seems acceptable. In an­other series of eyes with neovascular glau­coma, 33% were enucleated within 18 months of the onset of the disease.18 In our series, only three eyes were eventually removed. At this time, cyclocryotherapy seems the proce­dure of choice for neovascular glaucoma.

SUMMARY

The effect of cyclocryotherapy upon 38 eyes with rubeosis iridis and neovascular glaucoma was evaluated retrospectively. With one or more treatments, a reduction in pressure of more than 50% of the preop-erative level was attained in 26 eyes, and in 24, pressures were maintained below 20 mm Hg. No significant difference in response to therapy was noted in lightly and heavily pig-mented eyes. Eyes that were treated twice had significantly better pressure control compared to the results in those treated only once, and they showed no higher incidence of in­duced chronic hypotony. The duration, tem­perature, and methods of the cryoapplication did not correlate with the final pressure re­sponse. In spite of control of the pressure, the visual prognosis for such eyes remained poor. When compared to other glaucoma procedures, cyclocryotherapy appeared to be the procedure of choice for eyes with neo­vascular glaucoma.

VOL. 74, NO. 5 RUBEOSIS IRIDIS 867

R E F E R E N C E S

1. Marr, W. G. : The treatment of glaucoma with cyclodiathermy. Am. J. Ophth. 32:241, 1949.

2. Meyer, S. J. : Diathermy cauterization of the ciliary body for glaucoma. Arch. Ophth. 41:417, 1949.

3. Bietti, G. B. : Notes on the development of cryosurgery in ophthalmology. Tr. Ophth. Soc. U.K. 88:79, 1968.

4. De Roetth, A., Jr. : Cryosurgery for the treat­ment of glaucoma. Am. J. Ophth. 61:443, 1966.

5. Boles-Carenini, B., and Orzalesi, N.: An ex­perimental and clinical study of aqueous dynamics and ultrastructural changes of the ciliary body after cyclocryotherapy. J. Cryosurg. 1:48, 1968.

6. Haye, G, Haut, J., and Mondon, A. : Résultats de cryocoagulation du corps ciliare dans certain glau­comes. Bull. Soc. Opht. Franc. 67:383, 1967.

7. Hilsdorf, C. : Erfahrungen mit der Kältebe­handlung des Ziliarkörpers beim Glaukom. Klin. Mbl. Augenheilk. 156:63, 1970.

8. Leszek Szymanski, C, Furman, J., Lech, M., and Szymanski, M. : Criociclocoagulation. Coagula­tion del Cuerpo Ciliar por la Accion del Frio, XXI Concilium Ophthalmologica, Mexico. Mexico City,

Amsterdam, Excerpta Medica Foundation, 1970, p. 1043.

9. Zenteno, E. R., Verdaguer, J., Anguita, J., and Miranda, M. : Ciclocrioterapia en el Tratamiento del Glaucoma Secundario. Arch. Chil. Oft. 22:55, 1965.

10. Chenoweth, R. G.: Sequential cyclocryosur-gery. Audio-Dig. Ophth. 9 : tape, 1971.

11. De Roetth, A., Jr. : Cryosurgery for the treat­ment of advanced chronic simple glaucoma. Am. J. Ophth. 66:1034, 1968.

12. : Ciliary body temperatures in cryo­surgery. Arch. Ophth. 85:204, 1971.

13. Mazur, P. : Physical-chemical factors under­lying cell injury in cryosurgical freezing. In Rand, R. W., Rinf ret, A. P., and von Leden, H. : Cryo­surgery. Springfield, Charles C Thomas, 1968, p. 50.

14. Cahan, W. G. : Cryosurgery : The management of massive recurrent cancer. In Von Leden, H., and Cahan, W. G : Cryogenics in Surgery. New York, Medical Examination Publishers, 1971, p. 208.

15. Müller-Jensen, K. : Zur operativen Behandlung des "hämorrhagischen." Glaukoms. Klin. Mbl. Au­genheilk. 146:718, 1965.

16. Hohl, R. D., and Barnett, D. M.: Diabetic hemorrhagic glaucoma. Diabetes 19:944, 1970.

O P H T H A L M I C M I N I A T U R E

For deadly fear can time outgo, And blanch at one the hair. H a r d toil can roughen form and face, And want can quench the eye's bright grace ; N o r does old age a wrinkle trace, More deeply than despair.

Sir Walter Scott Marmion