PREGNANCY AND DIABETIC RETINOPATHY

GLEN PAUL JOHNSTON, M.D.St. Louis, Missouri

Diabetic retinopathy is one of thelong-term complications of juvenile-onsetdiabetes that is more likely to occur as theduration of diabetes increases. This prob­lem usually makes its appearance about15 years after the onset of diabetes, andthus can be expected in young women 20to 30 years of age who developed diabeteswhen they were 5 to 15 years old. Sincethe years between ages 20 and 30 are alsothe peak child-bearing years the onset orprogression of diabetic retinopathy dur­ing a pregnancy may be coincidental or itmay be related to the dramatic endocrin­ologic and metabolic changes associatedwith pregnancy.

Pregnancy and diabetes certainly com­plicate each other in many ways. Theseverity of the complications increaseswith the duration of the diabetes and thelack of consistent control.! In recentyears, however, advances in the treat­ment of juvenile-onset diabetes and ob­stetric care have allowed many moreyoung diabetic women to reach theirchild-bearing years with reasonably goodhealth and the capability of becomingpregnant.F There are still risks of fetalmortality and of morbidity for bothmother and child, but they are decreas­Ing." Beetham." in 1950, described theresults of 18 pregnancies in 12 womenwith proliferative diabetic retinopathy,and reported that none of these patientshad a successful pregnancy while main­taining useful visual acuity. Since that

From the Department of Ophthalmology, Wash­ington University School of Medicine, St. Louis,Missouri.

Reprint requests to Glen Paul Johnston, M.D.,Retina Consultants, Ltd., Suite 5103 Queeny Tower,4989 Barnes Hospital Plaza, St. Louis, MO 63110.

time, photocoagulation and other proce­dures for the treatment of diabetic reti­nopathy have become available and havealtered this dismal prognosis.

A prospective study to prove a causalrelationship between pregnancy and de­terioration of diabetic retinopathy wouldbe practically impossible to design. Wehave, however, collected data on thebehavior of diabetic retinopathy duringpregnancy and the effect of photocoagula­tion treatment in 30 patients. We select­ed records of 30 women with juvenile­onset diabetes who had never beenpregnant and attempted to match eachwoman in the pregnant group as closelyas possible with another patient for ageand duration of diabetes. These retro­spective data, covering a 20-year period,provide valuable information about thevisual prognosis for these prospectiveyoung mothers with diabetic retinopathy,and they provide a basis for evaluatingthe traditional obstetric recommendationof therapeutic abortion for patients withdiabetic retinopathy.

SUBJECTS AND METHODS

Thirty patients with juvenile-onsetdiabetes had repeated complete ophthal­moscopic evaluations, including fundusphotography, during and after a total of35 pregnancies. In some cases the initialocular studies were done before preg­nancy, and in others at various timesduring pregnancy. These patients werenot selected from the diabetic popula­tion at random; they were referred here be­cause of a tentative diagnosis of diabeticretinopathy. They make up a small per­centage (0.5%) of the total population ofpatients with diabetic retinopathy seenhere between 1961 and 1980. Only pa-

AMERICAN JOURNAL OF OPHTHALMOLOGY 90:519-524, 1980 519

520 AMERICAN JOURNAL OF OPHTHALMOLOGY OCTOBER, 1980

tients observed to the end of pregnancyand for at least six months after (meanfollow-up was five years) were included inthis study. Their ages ranged from 20 to35 years at the time of conceiving, with amean of 25 years; the duration of diabetesranged from 7 to 34 years, with a mean of17 years. Remarkably, seven patientswere 30 years or older during pregnancy,and four had had diabetes for more than20 years.

For the purpose of comparing thecourse of diabetic retinopathy and resultsof treatment without pregnancy, 30patients were selected who had neverbeen pregnant and who matched thepregnant group on the basis of age andduration of diabetes. Their ages rangedfrom 18 to 35 years, with a mean of 25years. The duration of diabetes rangedfrom 11 to 31 years, with a mean of 17years (Table 1). The nonpregnant womenhad retinopathy similar to that found inthe pregnant group (Table 2), suggestingthat the duration of diabetes is moreimportant in determining the severity ofocular problems than the presence orabsence of pregnancy.

In addition to similar ocular findings,the two groups were parallel in otherways, including the fact that seven pa­tients in each group died of renal failureor myocardial infarction. The deaths in

TABLE 1

COMPARATIVE DATA FOR THE TWO GROUPS

Pregnant NonpregnantData Patients Patients

Age (yrs)Range 20-35 18-35Mean 25 25

Duration of diabetes (yrs)Range 7-34 11-31Mean 17 17

Follow-up (yrs)Range 1-13 1-15Mean 5 5

TABLE 2

CLASSIFICATIONS FOR 60 PATIENTS (120 EYES)

Pregnant NonpregnantClassification Patients" Patients

B 21 19I 5 5

II 16 20III 10 12IV 7 4D 1 0

*Patients with two pregnancies were classified atthe time of the second pregnancy.

the nonpregnant group occurred one toseven years after their first retina consul­tations, with a mean of four years; in thepregnant group deaths occurred two tonine years after pregnancy, with a meanof five years.

Classification ofdiabetic retinopathy­Each eye was classified at each examina­tion by the Okun-Cibis systern.! Thisclassification system quickly and concise­ly conveys the essential information.

"B" indicates background or simpleretinopathy with no preretinal prolifera­tion. The degree of fibrovascular prolif­eration present is designated as follows:

I, three or fewer areas of surfaceneovascularization or 3 disk diameters ofproliferation;

II, four or more such areas, or thepresence of flat disk neovascularization;

III, elevated proliferation into thevitreous cavity less than 4 disk diametersin size; and

IV, proliferation into the vitreousmore than 4 disk diameters in extent.

"D" indicates dense hemorrhage total­ly obscuring the fundus.

Treatment-Xenon photocoagulationwas performed under retrobulbar anes­thesia in most cases. Argon laser photoco­agulation was also performed as supple­mentary therapy in a few patients. Theexact techniques have been describedelsewhere.P No attempt was made to

VOL. 90, NO. 4 PREGNANCY AND DIABETIC RETINOPATHY 521

standardize treatment for the patients inthis study, and treatment was adminis­tered as frequently and extensively as thecondition of the eye warranted. Therewere no adverse effects on the pregnan­cies in those patients who were treatedwith photocoagulation. Two patients ineach group underwent pituitary ablationas their initial therapy.

RESULTS

Pregnant group--Thirteen of thepregnancies were interrupted before thethird trimester, nine by spontaneousabortion and four by therapeutic abor­tion. Twenty-one patients gave birth tolive infants (20 by cesarean section); onestillborn infant was delivered by cesar­ean section.

Many changes occurred in the retinop­athy during pregnancy. Most eyes nottreated with photocoagulation beforepregnancy deteriorated in both visualacuity and grade of classification; theseeyes were therefore treated. Some of theeyes treated before pregnancy also dete­riorated, but generally to a lesser de­gree. In considering the changes in theeyes during pregnancy, it is important todifferentiate between those with back­ground retinopathy and those with pro­liferative retinopathy. One must also dis­tinguish patients treated before theybecame pregnant (whose classificationmay have been converted from prolifera­tive to background retinopathy by treat­ment) from those not treated before con­ceiving.

BACKGROUND RETINOPATHY IN BOTHEYES-Eight patients had backgroundretinopathy in both eyes before pregnan­cy. One of these patients had had prolif­erative retinopathy (Class II) in both eyestwo years before conceiving. The prolif­erative retinopathy had been successfullytreated and converted to backgroundretinopathy. Her pregnancy was termi­nated by spontaneous abortion at eightweeks of gestation, and no deterioration

in her retinal condition occurred. Anotherpatient had had background retinopa­thy which had not changed with her firstpregnancy, but which deteriorated toproliferative retinopathy two years laterbefore a second pregnancy. The other sixwomen all experienced deterioration oftheir retinopathy which changed frombackground to proliferative stages duringpregnancy.

BACKGROUND RETINOPATHY IN ONEEYE-Five patients had background reti­nopathy in one eye and proliferativeretinopathy in the other at the time ofconceiving. One patient was unusual inthat she had had transphenoidal pituitaryablative surgery four years before con­ceiving in an effort to ameliorate floridproliferative retinopathy. The pituitaryablation was obviously incomplete andone eye was treated with extensive photo­coagulation, which eliminated the prolif­erative tissue and converted the prolif­erative to background retinopathy. Theuntreated eye, which had remained sta­ble after the pituitary surgery, deteriorat­ed and developed vitreous hemorrhage inthe last trimester of pregnancy, while thetreated eye maintained its "B" classifica­tion. Two other eyes in this group hadalso been converted from the prolifera­tive stage to background retinopathybefore pregnancy by photocoagulation,and no deterioration occurred. The re­maining two eyes (untreated) both deteri­orated from background to proliferativeretinopathy during pregnancy.

Fifteen of the 21 eyes in the B classifi­cation progressed to proliferative reti­nopathy during pregnancy; of the six thatdid not, five had been previously treatedwith photocoagulation.

These data indicate an extremely poorprognosis for background retinopathyduring pregnancy. However, these casescannot be used to assess the frequency ofconversion from background to prolifera­tive retinopathy during pregnancy sincethey were all selected cases in which the

522 AMERICAN JOURNAL OF OPHTHALMOLOGY OCTOBER, 1980

TABLE 3

VISUAL ACUITIES OF 60 PATIENTS

TABLE 4

VISUAL ACUITIES OF 6/12 (20/40) OR BETTER ATLATEST EXAMINATION

cies maintained a visual acuity of 6/12(20/40) in at least one eye.

Nonpregnant group-Eight patientshad background retinopathy in both eyeswhen first examined; four did not deterio­rate to proliferative retinopathy duringthe follow-up period. All eight eyes in theremaining four patients developed prolif­erative retinopathy within three yearsand required photocoagulation.

Three patients had background reti­nopathy in one eye and proliferative

Pregnant NonpregnantVisual Acuity* Patients Patients

6/12 (20/40) or betterInitial 24 27Latest 23 24

6/15 to 6/30(20/50 to 20/100)

Initial 6 3Latest 2 4

6/90 to 6/120(20/200 to 20/400)

Initial 0 0Latest 2 0

Counting fingersInitial 0 0Latest 3 2

"In at least one eye.

52

116o

24

No. of Eyes

12

1352

23

Pregnant NonpregnantPatients Patients

Total

B (not treated)IIIIIIIV

Classification atTime of Treatment

referring physician had noted retinopa­thy severe enough to warrant referral forpossible treatment.

Twenty-seven patients (49 eyes) hadproliferative retinopathy at the time ofconceiving. Of these, 14 had alreadybeen treated with photocoagulation in atleast one eye before pregnancy. A total of24 eyes had undergone photocoagulationbefore pregnancy; seven of these deterio­rated during pregnancy (seven of 24 or29%). Of the 30 not treated before preg­nancy, 26 (87%) deteriorated. In onepatient whose eyes had not deterioratedduring pregnancy, the proliferative reti­nopathy worsened nine months after de­livery while she was undergoing dialysisfor renal failure. The other three patientsall had avascular inactive fibrotic retinitisproliferans, which had not changed sincetheir pregnancies.

Of the patients who had visual acuitiesof 6/12 (20/40) or better at the last exami­nation, ten had interrupted (ten of 13 or77%) and 15 uninterrupted pregnancies(15 of 22 or 68%).

Of the 49 eyes with proliferative reti­nopathy, 33 (67%) deteriorated duringpregnancy; 26 were treated with photoco­agulation but seven were considered toofar advanced for treatment. Of 26 treatedeyes, 22 (85%) were considered successeson the basis of elimination of neovasculartissue and stabilization of vision.

The total group of 27 patients withproliferative retinopathy included onlythree patients who became blind duringor immediately after their pregnancies.The vast majority have useful visualacuities, 22 of the 27 patients (81%) withproliferative retinopathy have visual acui­ties of6/12 (20/40) or better in at least oneeye (Tables 3 and 4).

The final visual outcome was essential­ly the same in the women who hadinterrupted pregnancies as in those whocarried babies to full term (Table 5). Fourof the five patients who had two pregnan-

VOL. 90, NO. 4 PREGNANCY AND DIABETIC RETINOPATHY

TABLE 5

VISUAL ACUITY RESULTS FOR PREGNANT PATIENTS

523

Pregnancies"

UninterruptedInitialLatest

InterruptedInitialLatest

No. of Eyes

22

13

Visual Acuities of6/12 (20/40) or Better'[

1617

1210

"There were 35 pregnancies in 30 women.tIn at least one eye.

retinopathy in the other. All three of theeyes classified as B deteriorated to prolif­erative retinopathy within 18 monthsafter the first examination.

Twenty-five patients (47 eyes) had pro­liferative retinopathy when first exam­ined. All but two were treated withphotocoagulation. The two exceptionshad pituitary ablation surgery (four eyes).Two patients lost all useful vision in botheyes; 24 patients (80%) retained visualacuities of6/12 (20/40) or better at the lastfollow-up visit.

DISCUSSION

Many questions can be raised about theadvisability of pregnancy for a womanwith juvenile-onset diabetes and retinop­athy. There are medical, ethical, relig­ous, and socioeconomic issues involved.White asked; "Why permit or encourageyoung women with diabetes to bear chil­dren?" She answered her own question:"To many, to nearly all, life lacks mean­ing without successful childbearing. "After 45 years of experience withjuvenile-onset diabetes, White recog­nized only two indications for termina­tion of pregnancy in diabetes: prolifera­tive retinopathy and renal failure. 7

Cassar and associates'' reviewed pub­lished reports on diabetic retinopathyand pregnancy and described 15 patients,

four of whom had proliferative retinopa­thy. Two of these patients underwentphotocoagulaion during pregnancy andmaintained normal vision. Cassar andassociates concluded that although dia­betic retinopathy may progress duringpregnancy, it is not an absolute contrain­dication, and the use of photocoagulationfurther improves the prognosis.

Hercules and associates" studied thecourse of proliferative diabetic retinopa­thy with disk neovascularization in 11patients during and after 13 pregnancies.Even with minimal argon laser therapy,only 9% became blind; and none hadvisual acuities of less than 6/60 (20/200).They concluded that therapeutic abortionand sterilization cannot be justified forophthalmic reasons.

Our experience with diabetic retinopa­thy in pregnancy is perhaps biased by ourreferral practice. The prognosis however,even in cases of proliferative diabeticretinopathy, is surprisingly good with theuse of photocoagulation. This is particu­larly true for patients treated beforeconceiving, but applies even to those firsttreated during pregnancy. The compari­son between pregnant and nonpregnantwomen with juvenile-onset diabetesshows that long-term visual efficiency isalmost equal for the two groups.

A young woman with juvenile-onset

524 AMERICAN JOURNAL OF OPHTHALMOLOGY OCTOBER, 1980

diabetes who wishes to have a childshould plan to become pregnant as earlyas possible. A careful examination fordiabetic retinopathy is necessary; if pres­ent, it should be treated before pregnan­cy. Patients with background retinopathyshould be carefully observed duringpregnancy; if proliferative retinopathydevelops, it should be treated with photo­coagulation.

Proliferative diabetic retinopathy isneither an absolute contraindication topregnancy nor an absolute indication fortherapeutic abortion. It is, however, stilla serious threat to the mother and aprobable cause of morbidity to bothmother and child. Proliferative retinopa­thy, along with other long-term complica­tions of diabetes, must be assessed ineach individual patient. If the prospec­tive mother does not have an intensedesire for a child, proliferative diabeticretinopathy can be considered stronggrounds for a therapeutic abortion.

SUMMARY

Diabetic retinopathy can be expectedto progress during the term of pregnan­cy. A retrospective study indicated thatphotocoagulation was successful in pre-

serving vision in 70 to 80% of 30 pregnantdiabetic patients as well as in a similargroup of nonpregnant patients withjuvenile-onset diabetes. Proliferative dia­betic retinopathy, in and of itself, is notan absolute indication for therapeuticabortion.

REFERENCES

1. White, P.: Diabetes mellitus in pregnancy.Clin. Perinatol. 1:331, 1974.

2. Younger, D.: Management of diabetes andpregnancy. In Sussman, K. E., and Metz, R. J. S.(eds.): Diabetes Mellitus. New York, American Dia­betes Association, 1975, pp. 135-145.

3. Hare, J. W., and White, P.: Pregnancy indiabetes complicated by vascular disease. Diabetes26:953, 1977.

4. Beetham, W. P.: Diabetic retinopathy in preg­nancy. Trans. Am. Ophthalmol. Soc. 48:205, 1950.

5. Okun, E., and Cibis, P. A.: The role of photo­coagulation in the therapy of proliferative diabeticretinopathy. Arch. Ophthalmol. 75:337, 1966.

6. Okun, E., Johnston, G. P., and Boniuk, I.:Management of Diabetic Retinopathy. A Stereoscop­ic Presentation. St. Louis, C. V. Mosby Co., 1971.

7. White, P.: Pregnancy and diabetes. In Marble,A., White, P., Bradly, R. F., Krall, L. P. (eds.):Joslin's Diabetes Mellitus. Philadephia, Lea & Feb­iger, 1971, pp. 581-598.

8. Cassar, J., Kohner, E. M., Hamilton, A. M.,Gordon, H., and Joplin, G. F.: Diabetic retinopathyand pregnancy. Diabetologia 15:105, 1978.

9. Hercules, B. L., Wozencroft, M., Gayed, I. I.,and [eacock, J.: Peripheral retinal ablation in thetreatment of proliferative diabetic retinopathy duringpregnancy. Br. J. Ophthalmol. 64:87, 1980.