How to Manage Glaucoma in Women

Hormones and gender may play a larger role than was thought previously.

According to estimates, there will be an increase in how many Americans are suffering from glaucoma from 60 million to 80 million by the year 2020.  Given the fact that women outlive and outnumber men, it will result in a high number of patients needing Optometric care.  As we are reviewing risk factors for the blinding disease, may be hormonal and gender factors need to factor into our decision-making process.

Since glaucoma is a disease affecting the aged optic nerve, it makes sense that the individuals living longer will be the ones with an increased risk.  Since glaucoma is a progressive disease, it is critical to diagnose the condition and treat it earlier, particularly those who might have silent risk factors, like being exposed to endogenous estrogen.

Numerous epidemiologic studies have been conducted in order to determine whether or not there is a difference between gender when it comes to the incidence of glaucoma.  There have been no conclusive findings when it comes to primary open-angle glaucoma due to the variances in study populations and designs.  No difference was shown in the Beaver Dam and Baltimore Studies, there was an increase incidence shown for women in the Blue Mountain Study, and the Rotterdam, Barbados and Framingham studies show increased incidence in men.

Secondary Glaucoma

It is more likely that women will be more susceptible for narrow-angle glaucoma when looking at some of less common forms.  A theory has been around a long time that the physical difference was the shorter axial length.  However, new evidence coming from Wang utilizing anterior segment tomography shows that it might be related as well to curvature variations and iris thickening.  Many studies from Scandinavia and U.S. are in agreement that women are less at risk when it comes to pigmentary dispersion glaucoma and more at risk in terms of pseudoexfoliation syndrome.

However, since those forms might be more aggressive, their management should be as well.  Low tension glaucoma is the greatest concern since it is the form that is most under diagnosed.  However, the CNTGS reports women are at a greater risk.  That is most likely due to glaucoma having multi-factorial causes, like vasospasm disorders, women may develop include reduced circulation to feet and hands, headaches, migraine and low blood pressure which might contribute to blood flow loss into the optic nerve.

Pregnancy Effects

It is critical to view the pregnancy state as a factor both in glaucoma treatment and diagnosis.  As pregnancy is delayed by women in their late thirties and forties, and since glaucoma is known to affect people as they age, that is why the initial glaucoma diagnosis might take place during pregnancy.  However, according to studies, in the second trimester, regular patients have a 10-20 percent IOP reduction.  An even higher reduction is experienced by ocular hypertensive patients.  During Weeks 24 through 30, it is 25 percent.  Several theories attempt to explain why this might take place.  Maybe uveo-scleral flow is increased by hormonal changes.  We do know that as women are preparing to deliver, other ligaments soften, and maybe this mechanism is also applicable to aqueous outflow.

Treatment Throughout Pregnancy

The finding provides the patient with some protection throughout pregnancy and it might be a safeguard to delaying management.  If the decision is made that a patient needs to either continue or start treatment, potential teratogenic effects must be taken into consideration.  Since a majority of glaucoma treatment is topical, remember that 80 percent of its drop drains to the nasolacrimal duct, leading to systemic absorption.  To reduce this, all steps need to be taken, like closing one’s eyes for a couple of minutes after instillation, wiping excess and punctual occlusion.

Brimonidine is the only real Category B glaucoma agent.  However, numerous glaucoma specialists agree that this risk-benefit ratio may make it possible for other medications to be used throughout pregnancy like timolol.  Many individuals will stop using it a couple of weeks before delivery in order to lessen any possible effects on the baby.  Orals need to be avoided, but topical carbonic anhydrase inhibitors might be indicated.

The prostaglandin category, theoretically, is contraindicated on account of its potential for inducing premature labor.  However, during lactation, these drugs are safe to use.  Keep in mind that all drops end up in the breast milk.  That is why the best thing to do is take single daily-dose medications right before the infant’s longest sleep interval.  If multiple doses are necessary, it is recommended that the patient breast feed right before instillation.  Numerous women also suffering from serious dry eye.  This can result in the use of beta-blockers being prohibited, which can make it harder to get an adequate amount of IOP control and more surgical intervention becoming necessary for the disease.

One potential concern is that the patient may be at risk for acute angle closure due to the factor that labor may end up precipitating an angle closure.  During pregnancy, laser peripheral iridotomy (LPI may be safely performed through an upright position and topical anesthesia being used during the procedure.  Those with a pre-existing glaucoma condition before pregnancy, it might be a more severe form because of earlier onset age.  During a natural childbirth, IOP will be slightly elevated.  That is why, if there is questionable control, a Cesarean section delivery should definitely be discussed.

Estrogen’s Role

There have been several studies that have looked into an estrogen’s role in glaucoma development.  It is known that estrogen offers neuroprotection.  However, even within gender, a role is played by the source of estrogen.  To summarize, women with late onset of menopause and early menses are exposed to endogenous estrogen longer.  It is shown this is protective glaucoma.

The Rotterdam Study results show that if natural menopause takes place before an individual reaches 45 years old, there is a 2.3 times higher risk for developing glaucoma, including when there is hormone replacement therapy.  Australia’s Blue Mountain Study shows that late onset of early menopause with greater than 45 years old or menarche in older than 13 years old, increases risk.   The U.S. Nurses Health Study came to the conclusion that later menopause, with onset at older than 54 years old, showed a lower risk.  Finally, the Mayo Clinic studies indicate that women with hysterectomies at younger than 43 years old had increased risk for developing glaucoma.

The role that iron plays is another consideration.  It causes oxidative stress.  During menses, women are frequently iron deficient, and it can end up having a protective effect.

When looking at exogenous estrogen, like oral contraceptives or hormone replacement therapy (HRT), the findings can vary.  For post-menopausal women who are on HRT, the Women’s Health Initiative and Estrogen Replacement Study, published in 2002 and 1998 respectively, indicated a risk reduction of 0.40 percent for POAG for each month of therapy.  In the U.S. today, HRI is extremely targeted for symptomatic women (symptoms including osteoporosis, urogenital atrophy and hot flashes).  The benefit is therefore limited due to a reduction in its use.  Pre-menopausal women on oral contraceptives are contrary.  The Nurses Health Study looks at patients during the time period of 1980 to 2006.  It showed that using oral contraceptives for five years or more resulted in a 25 percent increased risk for primary open-angle glaucoma.  Most likely the formula is what caused the difference in the exogenous sources as well as the physiological outcome.  Progestin is contained in oral contraceptives, which suppresses ovulation, resulting in natural hormonal patterns being altered.

There have been extensive studies on estrogen’s role within the central nervous system.  It is believed that some of the findings might be applicable to the optic nerve and retinal health.   Estrogen receptors are expressed by retinal ganglion cells, and that might contribute to Neuro-protection.  Extracellular matrix production is increased by estrogen.  It may provide the optic nerve head protection from axonal damage.  Since smooth muscle control is regulated by estrogen, it might enhance blood flow into the optic nerve.  Some cancer agents might be anti-estrogen, which means careful monitoring is necessary.

Women In The Caregiver Role

Women frequently manage the health care of their families and are caregivers.  So they might indirectly affect the detection and incidence of glaucoma.  The British Journal of Ophthalmology recently published a study from India that showed that five percent of 1,259 pediatric glaucoma cases were steroid induced based on steroids being overused for vernal conjunctivitis or severe GPC.  Children are more strongly affected by steroids at shorter duration and lower dosing compared to adults.  That is why monitoring IOP is important and why treatment should be discontinued in a timely fashion.  Since mothers may be instilling medications as well as treating conditions that are recurring, it is very important for them to be aware of what the potential risks are.

Glaucoma In Mature Individuals

As women become older, dementia starts to become a serious health concern.  Successfully treating glaucoma depends on compliance and patients’ ability for self-administering their medications is low due to loss of memory.  Since glaucoma and cognitive impairment both have a vascular risk factor in common, the relationship between glaucoma and Alzheimer’s disease has been reviewed.

A relationship has not been shown in past U.S. and European studies.  However, a population-based study from Taiwan that was recently published has shown a relationship.  The study looks at co-morbidity factors and ICD codes in more than 15,000 patients.  What was interesting about this study was that women with dementia, compared with the controls, were more likely to have had a prior open-angle glaucoma diagnosis.  Other studies have indicated women with glaucoma having vision loss that is more severe.  This could be due to late diagnosis, financial issues or longevity.  Lack of visual stimulation and sensory impairment can contribute to the progression of cognitive loss rather easily.  Other similarities between Alzheimer’s Disease and elevation in intraocular pressure, which includes amyloid plaques and decreased cerebro-spinal fluid in the retinal ganglion cells and brain have been discussed as well.

Lifestyle

The new saying these days is that 50 is the new 40.  Well, 70 is also the new 60!  Individuals who are this age have more active lifestyles compared to previous generations and work hard at staying healthy.  It may include participating in activities like golf, yoga and sex as well.

Depending on activity level, lateral extensions in golf and inversion in yoga, have been shown to raise intraocular pressure.  It has been shown that sleeping with one’s head elevated slightly to 30 degrees while using two pillows decreases IOP by as much as 20 percent.  This position is very common for women this age since it is more likely they will be making their weekly visits to the hair salon for their up-do hairstyles.  They will also likely maintain this style in between visits.

When it comes to people wanting to maintain their sex appeal and beauty, age doesn’t discriminate.  The most commonly discussed, treatment is erectile dysfunction that has become increasingly more effective.  An increasing number of seniors are sexually active these days.  It was thought for a long time that erectile dysfunction was a kind of side effect from using beta blockers topically or systemically for glaucoma.  Contrary to this belief, there appears to be a correlation between glaucoma diagnosis and ED, and not its treatment.  Since women frequently take care of the health needs of their spouses, it is a discussion that needs to be heard.

Ask Questions

Previously, glaucoma’s pertinent history included trauma, race, age and family history.  These days we need to ask additional questions.  As has been seen, hysterectomy, use of HRT/OC, and age of menses can play key roles.  Discussing childbearing might have been only in passing previously, however this information might be significant now since the choice is often delayed.  Our optic nerves also age.  Numerous men don’t disclose every medication they take or their ED diagnosis since they don’t think their eyes are affected.  We might need to ask their partners specifically about this.  Lifestyle choices that might focus on our gender more should also be discussed.  Future treatment, given some findings, might become more targeted towards hormonal control.  Women live longer globally.  It is very important to remember this when making a determination on when to treat and target IOP.

References

1. Vajaranant TS, Nayak S, Wilensky JT, Joslin CE. Gender and glaucoma: what we know and what we need to know. Curr Opin Ophthalmol. 2010 Mar;21(2):91-9.

2. Takusagawa H, Mansberger S. Do Ethnicity and Gender Influence Glaucoma Prevalence? Ophthalmology Management. Available at: http://www.ophthalmologymanagement.com/articleviewer.aspx?articleID=106702. Accessed 12/28/15.

3. The Eye Diseases Prevalence Research Group Prevalence of open-angle glaucoma among adults in the United States. Arch Ophthalmol. 2004 Apr;122(4): 532–538.

4. Leske MC, Connell AM, Schachat AP, Hyman L. The Barbados Eye Study. Prevalence of open angle glaucoma. Arch Ophthalmol. 1994 Jun;112(6):821-9.

5. Leske MC, Connell AM, Wu SY, Nemesure B, Li X, Schachat A, Hennis A. Incidence of open-angle glaucoma: the Barbados Eye Studies. The Barbados Eye Studies Group. Arch Ophthalmol. 2001 Jan;119(1):89-95.

6. Kang JH, Loomis S, Wiggs JL, Stein JD, Pasquale LR. Demographic and geographic features of exfoliation glaucoma in 2 United States-based prospective cohorts. Ophthalmology. 2012 Jan;119(1):27-35.

7. Wang B, Sakata LM, Friedman DS, Cahn YH He M, Lavanya R, Wong TY, Aung T. Quantitative iris parameters and association with narrow angles. Ophthalmology. 2010 Jan;117(1):11-17.

8. Kang JH, Lookis S, Wiggs JL, Stein JD, Pasquale LR. Demographic and geographic features of exfoliation glaucoma in 2 United States-based prospective cohorts. Ophthalmology. 2012 Jan;119(1); 27-35.

9. Wang D, He M, Wu L, Yaplee S, Singh K, Lin S. Differences in iris structural measurements among American Caucasians, American Chinese and mainland Chinese. Clin Experimental Ophthalmol. 2012 Mar;40(2): 162-9.

10. Kamal D, Hitchings R. Normal tension glaucoma—a practical approach. Br J Ophthalmol. 1998 Jul;82(7):835-40.

11. Tehrani S. Gender difference in the pathophysiology and treatment of glaucoma. Curr Eye Res. 2015 Feb;40(2):191-200.

12. Razeghinejad MR1, Tania Tai TY, Fudemberg SJ, Katz LJ. Pregnancy and glaucoma. Surv Ophthalmol. 2011 Jul-Aug;56(4):324-35.

13. American Academy of Ophthalmology. Drugs and Pregnancy. Focal Points: Clinical Modules for Ophthalmologists. September 2007

14. Johnson SM, Martinez M, Freedman S. Management of glaucoma in pregnancy and lactation. Surv Ophthalmol. 2001 Mar-Apr;45(5):449-54.

15. Pasquale LR, Rosner BA, Hankinson SE, Kang JH. Attributes of female reproductive aging and their relation to primary open-angle glaucoma: a prospective study. J Glaucoma. 2007 Oct-Nov;16(7): 598-605

16. AltintaÅŸ O, Caglar Y, Yüksel N, Demirci A, KarabaÅŸ L. The effects of menopause and hormone replacement therapy on quality and quantity of tear, intraocular pressure and ocular blood flow. Ophthalmologica. 2004 Mar-Apr;218(2): 120-129.

17. Zhou X, Li F, Ge J, Sarkisian SR Jr, Tomita H, Zaharia A, Chodosh J, Cao W. Retinal ganglion cell protection by 17-beta-estradiol in a mouse model of inherited glaucoma. Dev Neurobiology. 2007 Apr;67(5): 603-616.

18. Vajarant TS, Pasquale LR. Estrogen deficiency accelerates aging of optic nerve. Menopause. 2012 Aug 19(8): 942-7.

19. Hulsman CA, Westendorp IC, Ramrattan RS, Wolfs RC, Witteman JC, Vingerling JR, Hofman A, de Jong PT. Is open-angle glaucoma associated with early menopause? The Rotterdam Study. Am J Epidemiol. 2011 July 15:154(2): 138-144.

20. Lee AJ, Mitchell P, Rochtchina E, Healey PR; Blue Mountain Eye Study. Female reproductive factors and open angle glaucoma: the Blue Mountain Eye Study. Br J Ophthalmol. 2003 Nov;87(11): 1324-8.

21. Pasquale LR, Kang JH. Female reproductive factors and primary open-angle glaucoma in the Nurse’s Health Study. Eye (Lond). 2011 May;25(5): 633-41.

22. Vajaranant TS, Grossardt BR, Maki PM, Pasquale LR, Sit AJ, Shuster LT, Rocca WA. The risk of glaucoma after early bilateral oophorectomy. Menopause. 2014 Apr; 21(4): 391–398.

23. Gupta S, Shah P, Grewal S, Chaurasia AK, Gupta V. Steroid-induced glaucoma and childhood blindness. Br J Ophthalmol. 2015 Nov;99(11):1454-6.

24. Quigley HA, Broman AT. The number of people with glaucoma worldwide in 2010 and 2020. Br J Ophthalmol. 2006 Mar;90(3);262-7.

25. Chung SD, Ho JD, Chen CH, Lin HC, Tsai MC, Sheu JJ. Dementia is associated with open-angle glaucoma: a population-based study. Eye (Lond). 2015 Oct;29(10):1340-6.

26. McCKinnon SJ. Glaucoma: ocular Alzheimer’s Disease? Front Biosci. 2003 Sep 1;8:s1140-56.

27. Berdahl JP, Allingham RR, Johnson DH. Cerebrospinal fluid pressure is decreased in primary open-angle glaucoma. Ophthalmology. 2008 May;115(5):763-8.

28. Weinreb RN, Cook J, Friberg TR. Effect of inverted body position on intraocular pressure. Am J Ophthalmol. 1984 Dec 15;98(6):784-7.

29. Buys YM, Alasbali T, Jin YP, Smith M, Gouws P, Geffen N, Flanagan JG, Shapiro CM, Trope GE. Effect of sleeping in a head-up position on intraocular pressure in patients with glaucoma. Ophthalmology. 2010 Jul;117(7):1348-51.

30. Seo H, Yoo C, Lee TE, Lin S, Kim YY. Head position and intraocular pressure in the lateral decubitus position. Optom Vis Sci. 2015 Jan;92(1):95-101.

31. Nathoo NA, Etminan M, PharmD, Mikelberg FS. Association between glaucoma, glaucoma therapies, and erectile dysfunction. J Glaucoma. 2015 Feb;24(2):135-7.

32. McKinley SM, Brambilla DJ, Posner JG. The normal menopause transition. Maturitas. 2008 Sep-Oct;61(1-2):4-16.

33. Miro F, Parker SE, Apsinall LJ, Coley J, Perry PW, Ellis JE. Sequential classification of endocrine stages during reproductive aging in women; the FREEDOM study. Menopause. 2005 May-Jun;12(3); 281-90.

34. Austad SN. Why women live longer than men: sex differences in longevity. Gend Med. 2006 Jun;3(2): 79-92.

Click Here to Leave a Comment Below 0 comments