The exact effects of pregnancy on the IOP in glaucoma are not entirely understood. Studies in nonglaucomatous subjects have shown a statistically significant decline in IOP during all trimesters of pregnancy compared with nonpregnant controls.2,3,4,5,6
IOP declines as pregnancy progresses, with a statistically significant decrease in IOP from the first to the third trimester. The fall of IOP is greater in nonhypertensive and multigravida patients compared to hypertensive and nulligravidae women, respectively.7,8
The only study in pregnant patients with ocular hypertension revealed that IOP declined by 24.4%, and about 61% of the total decrease occurred between the 24th and 30th weeks of pregnancy. The IOP decreased by 19.6%, and about 35% of the total decrease occurred between the 12th and 18th weeks of pregnancy in individuals without ocular hypertension.5
In other words, the decline in IOP was greater in patients with ocular hypertension. IOP has been found to be associated with systemic blood pressure levels in population-based studies.9,10
Hypertension is the most common disorder that occurs during pregnancy.11
Qureshi et al.6
measured IOP in normotensive and hypertensive pregnant patients at three trimesters. The results were compared with nonpregnant normotensive individuals as a control group. In all trimesters of pregnancy, IOP was found to be lower in nonpregnant control subjects. A significantly higher mean IOP was detected in third trimester of hypertensive pregnant women (P
< .05), as compared to third trimester normotensive pregnant women. The difference was 0.53 ± 1.5 mm Hg. The authors postulated that the physiologic basis for the IOP-blood pressure relationship in this population may be the result of an increased production of aqueous humor induced by increased blood pressure. However, Phillips and Gore7
found that the mean IOP of third trimester hypertensive pregnant women did not differ significantly from that of third trimester nonhypertensives.
The physiological mechanisms responsible for the decrease of IOP during pregnancy are not known. IOP reduction has been proposed to be caused by several factors: (1) an increase in uveoscleral outflow based on changes in the mother’s endogenous hormone levels, (2) a decrease in episcleral venous pressure reflecting an overall reduction of venous pressure in the upper extremities, and (3) decreased aqueous production due to a slight metabolic acidosis induced by the mother’s pregnant state and the effect of human chorionic gonadotropin (hCG) on the ciliary processes.12,13,14,15
hCG reduces IOP by stimulating the production of cyclic adenosine monophosphate that decreases aqueous humor production.16
In one study the rate of aqueous formation in seven pregnant patients showed no change during pregnancy, but IOP showed a consistently significant fall (17.1 mm Hg at 14 weeks to 13.0 mm Hg at 40 weeks), returning after delivery to values seen in early pregnancy. IOP reduction may thus be due to increased outflow, not to decreased aqueous production.13
Paterson and Miller17
found that during pregnancy the outflow facility rose steeply for about 20 weeks. It then underwent a sudden reduction followed by a slow recovery with another sharp decrease at term. Throughout pregnancy the estrogen and progesterone levels gradually rise and reach a peak at 40 weeks. Since these hormone levels rise gradually throughout pregnancy, the fall in IOP may not be attributable to progesterone and estrogen. Ziai et al.18
were also unable to find a statistically significant correlation while comparing the observed changes in outflow facility and the observed changes in the progesterone level. The pattern of change in outflow facility seems to follow closely that of relaxin serum level. Relaxin serum level rises to a peak at 20 weeks and then falls off completely from 20 to 24 weeks, and then reappears, rises to a maximum at parturition, and completely disappears again 48 hours later. This pattern seemed to follow closely that of the facility of outflow observed during pregnancy, when it consistently occurred in all cases at approximately 20 weeks. Wilke noted lower episcleral venous pressure in pregnant women.19
It has been reported that the reduction of episcleral venous pressure was consistent with the generalized reduction of peripheral vascular resistance during pregnancy.20
The increased outflow facility and consequently IOP reduction observed in pregnant patients is attributed to hormonal changes.2,17,18
Some case reports describe women with glaucoma whose IOPs have been difficult to control despite medical and surgical interventions.21,22
In a retrospective study conducted on 28 eyes of 15 pregnant glaucoma patients with varying severity and types of glaucoma, in 16 eyes the level of IOP remained stable during pregnancy with no associated loss of visual field. In five eyes there was progression within the field of vision while the level of IOP remained stable or increased, and in five eyes the level of IOP increased, but there was no progression of the damage to the visual field. In the remaining two eyes the data was inconclusive. Glaucoma medications were used to control the level of IOP in 13 of the 15 remaining patients.23
A 28-year-old woman had a controlled IOP with latanoprost for 5 years, but in pregnancy it increased to 30 mm Hg even after adding timolol and dorzolamide and receiving laser trabeculoplasty (LT). Finally, she underwent trabeculectomy without antimetabolites.24
All reports emphasize the importance of regular follow-up of pregnant patients with glaucoma. Although a population of patients may show decreasing IOP in pregnancy, an individual patient may develop worsening glaucoma and vision loss while pregnant.
Noncontact tonometers were shown to increase intraobserver agreement in IOP measured late in pregnancy and may be superior to both Goldmann and Schiotz tonometers in the management of pregnant patients.25
Although the Goldmann tonometer is regarded as a standard tonometer, in those pregnant patients who are reluctant to receive a topical anesthetic agent for IOP measurement the noncontact tonometry can be employed. However, there have been no teratogenic effects reported with the use of topical anesthetics.12,26
The reported corneal changes in pregnancy include a decrease in corneal sensitivity, with the largest changes late in pregnancy,27
and an increase in thickness during pregnancy.28
In a study of corneal curvature in pregnant women there was a statistically significant increase in corneal curvature during the second and third trimester which resolved postpartum or after the cessation of breast-feeding.29
Weinreb et al.28
measured central corneal thickness in 89 pregnant women and compared it with nongravid or postpartum controls and reported increased corneal thickness of 16 microns in pregnant subjects. The authors postulated that this increase may be the result of the generalized physiologic increase in water retention during the pregnant state. This observation of increased corneal thickness was confirmed by other investigators.18
Another study, however, evaluating the corneal thickness and curvature of 100 pregnant patients confirmed no difference between pregnant and nonpregnant women.30
In 27 patients, corneal thickness was recorded during the third trimester, and again 6 weeks postpartum. The corneal thickness was the same during pregnancy as it was after delivery.31
An increase in corneal thickness has not been observed consistently in all studies. If we propose that corneal thickness increases in pregnancy, we should expect higher IOP readings.
The importance of central corneal thickness for the diagnosis, management, and prognosis of glaucoma is well documented. IOP is underestimated in structurally thinner corneas, whereas it is overestimated in structurally thicker corneas. A major exception is corneal edema, which causes an underestimation of IOP despite thickening.32,33
Some studies showed increase in corneal thickness and curvature that can lead to overestimation of IOP measurement. The suggested cause of increase in corneal thickness is corneal edema that logically should lead to lower IOP readings. Additionally, it is well known that a change in the elasticity of ligaments and connective tissue occurs in pregnancy, and this tissue softening may extend to that of the corneoscleral envelope to produce reduced corneoscleral rigidity making applanation tonometry readings falsely low. The only available instrument for checking corneal biomechanical properties is the Ocular Response Analyzer, and we are aware of no study that has been conducted in pregnant women using this device yet. Finally, it is possible that IOP is not actually lower during pregnancy, but rather there is increased measurement error in pregnant women.
Newly developed Krukenberg’s spindles on the cornea have been observed early in pregnancy, and they tend to decrease in size during the third trimester and postpartum.34
The hormonal effects of estrogen, progesterone, and melanocyte stimulating hormone are postulated as the cause of this increased pigmentation and the increased facility of outflow is suggested as a possible cause of the clearing of pigment late in pregnancy.