Teratogenic effects have been associated with benzodiazepine use in pregnancy, but these effects are controversial [47]. Problems such as oral clefts, skeletal abnormalities, pyloric stenosis, inguinal hernias, hemangiomas, and cardiovascular defects have been reported with first- and second-trimester use, but other data do not support an association between malformations and fetal exposure to benzodiazepines [47]. Tables 4.32 and 4.33 list pregnancy and nursing information regarding the benzodiazepines [20,25,47]. Central nervous system depression and withdrawal symptoms may occur when benzodiazepines are used in the third trimester and through delivery, and neonatal withdrawal symptoms may be present at birth or may appear weeks later [47]. Neonatal symptoms are more likely with higher maternal doses and longer duration of benzodiazepine use. Patient discussion regarding benzodiazepine use during pregnancy requires conservative advice and caution [47]. It is certainly best to try to avoid benzodiazepines during pregnancy. If a patient is unable or unwilling to stop benzodiazepines because of a recurrence of disabling anxiety symptoms, she should be encouraged to use the lowest possible dose, preferably on an as-needed basis. If possible, discontinuation prior to the last 2 months of pregnancy is advisable, and the patient can restart immediately after delivery if not breast-feeding [47]. If a patient learns of a pregnancy while taking benzodiazepines, a thorough discussion and documentation of the risks and benefits of benzodiazepine use is warranted. Studies have shown that approximately 3% of all pregnancies end with an abnormal live-born infant delivered, and 3% of these infants are associated with exposure to a teratogen [47]. There is no compelling data that discontinuing benzodiazepines will decrease the 3% risk [47]. Stopping the benzodiazepine as soon as possible with a slow taper over several weeks should be encouraged. Benzodiazepines are excreted in breast milk, and despite studies supporting a low incidence of adverse effects and toxicity, the clinician is advised to use caution and assess the risks versus benefits of exposing infants to benzodiazepines in breast milk [47]. Highlights of Benzodiazepine Use in Anxiety Disorders [Adapted from refs. 2, 47, 48, 54] ? Selective serotonin reuptake inhibitors are the preferred treatment for anxiety disorders, but benzodiazepines are commonly used to treat anxiety and anxiety disorders, despite concerns about the risk of abuse and dependence. ? Benzodiazepines have a quicker onset of action than antidepressants and are well tolerated. They can also be used on an as-needed (prn) basis. ? Benzodiazepines are useful as primary and adjunctive therapy to antidepressants for the treatment of anxiety and anxiety disorders. ? Patients treated with benzodiazepines maintain benefits over time, and according to most studies, the doses remain the same or decrease for the majority of patients. ? Appropriate prescribing of benzodiazepines requires a careful evaluation of the patient including distinguishing situational anxiety from anxiety disorders such as generalized anxiety and panic disorder. ? Discussing benzodiazepine therapy with the patient, including expected benefits, common side effects, and potential risks, can help the patient feel more comfortable and facilitates compliance with treatment. ? Patients should be warned about common side effects such as potential sedation and psychomotor impairment, as well as the issue of physical dependence and the need to taper when the drug is discontinued after longer-term use. Caution the patient about operating machinery or dangerous appliances (including driving) as well as performing skilled tasks while taking benzodiazepines, especially early in treatment. Document the information in the patient’s chart. ? The clinician should advise the patient to avoid using alcohol and other sedating medications while taking benzodiazepines. ? When considering benzodiazepine therapy for elderly patients or patients with a current or lifetime history of substance abuse or dependence, the practitioner must be very cautious and thoroughly evaluate and discuss the risks and benefits with thorough documentation. ? When prescribing benzodiazepines, use the lowest effective dose. Understand physical dependence and use effective strategies for minimizing discontinuation symptoms. Patients with anxiety disorders who are treated with benzodiazepines should not be viewed as drug seekers. Without a history of substance abuse, there is little liability for abuse of benzodiazepines by patients. The practitioner must reevaluate the need for benzodiazepine treatment intermittently, using good clinical judgment and attempting to taper and discontinue when possible. ? Patients who have taken benzodiazepines for many years, have a good therapeutic response, and have no evidence for misuse or abuse may be allowed to continue their medication if necessary with proper follow-up. It is generally not clinically wise to switch medications in stable, comfortable patients just for the sake of removing the benzodiazepine.

Avastin® is useful for a variety of eye conditions;  it is principally used to treat wet macular degeneration and is becoming a popular option to treat diabetic macular edema.  On occasion, Avastin has also been useful, in my practice, to treat patients with proliferative diabetic retinopathy.

VEGF (Vascular Endothelial Growth Factor) also causes abnormal blood vessels to grow in cases of “wet” macular degeneration and … proliferative diabetic retinopathy.

Proliferative Diabetic Retinopathy (PDR) is defined by the presence of abnormal “neovascularization.”  These are abnormal proliferations of blood vessels that grow inside the eye.  In patients with diabetic retinopathy, the VEGF is produced in response retinal ischemia; retinal demand for oxygen exceeds the supply due to poor blood supply.  VEGF then causes neovascularization to develop.  This neovascularization can cause blindness by causing retinal detachments or neovascular glaucoma.

The  traditional treatment for proliferative diabetic retinopathy has been laser photocoagulation.  The laser treatment, called pan-retinal photocoagulation (PRP), has been the treatment of choice for years.  The PRP destroys enough tissue so that the available blood supply is adequate to meet the oxygen requirements of the tissue.  When this occurs the “ischemia” is cured, VEGF is no longer produced and the proliferative retinopathy becomes stable.

Occasionally, I have  patients that do not respond well, or completely, to pan-retinal photocoagulation.  Lately, on select cases, I have used Avastin as an alternative to pan-retinal photocoagulation for the treatment of proliferative diabetic retinopathy.

So far the treatment works well.  The neovascular tissue regresses quickly and I recheck patients every 4-6 weeks.  The injections do need to be repeated.

What Does This Mean? Pan-retinal Photocoagulation has been the gold-standard for the treatment of proliferative diabetic retinopathy.  The PRP can decrease light to dark adapatation, that is, it takes awhile to get used to light when coming out of a movie theater.  It is a difficult procedure to perform, but has been very effective over the years.  I consider it a good “fix.”

An alternative therapy is welcomed for two reasons.  Avastin injections are certainly easier to perform and seem not too affect the vision.  Avastin also treats the disease by a different mechanism and may increase the chances of achieving stability.  On the other hand, Avastin does NOT change the relative ischemia in the retina, that is, the oxygen demand is still greater than oxygen supply.  It may be less of a permanent “fix.”

“Randy”

Randall V. Wong, M.D.
Retina Specialist, Ophthalmologist
Fairfax, Virginia