Corneal issues and Herceptin

[bingy]

Hi, my mum is in her 3rd year on Herceptin and apart from pretty bad stomach bloating (any suggestions please, they look at us with surprise at the clinic when we mention this fact?) she is doing really well but has been suffering with dry eyes and recently she put some outdated drops in causing an inflammation. When she saw the specialist he said that as well as the inflammation caused by the drops, she has a deteriorating corneal problem. She can only see out of one of her eyes and cannot stop taking Herceptin. As a method of elimination I thought I would ask if anyone had a similar issue.
Many thanks and good wishes to you all.

[Lani]

Do they think the corneal abrasion is just from not having enough tears to lubricate the eyes and wash out particulates while living in an area with lots of particulate matter in the air, or from some other cause?

They have identified some ocular side effects of tamoxifen and AIs, but I hadn't read of any from herceptin(other than decreasing lacrimal secretions ie, tears).Will look further

[Lani]

actually did not find ocular issues in long article by Roche (haha) employee on side effects of herceptin given for metastatic bc--will still go over the label which comes with herceptin vials (available online @ genentech/roche website) to see if lists ocular side-effects

In the meantime, I found that herceptin is promising to PREVENT damage to sight caused by too many new bloodvessels forming on the cornea, usually in response to damage:

The inhibitory effects of trastuzumab on corneal neovascularization.
Güler M, Yilmaz T, Ozercan I, Elkiran T.
Department of Ophthalmology, School of Medicine, Firat University, Elazig, Turkey. meteglr@yahoo.com
Abstract
PURPOSE: To investigate the effect of systemic administration of trastuzumab in the prevention of experimentally induced corneal neovascularization in a rat model.
DESIGN: An experimental animal study.
METHODS: Sixteen male Wistar-Albino rats weighing 250 g to 300 g were used in the study. Silver nitrate sticks (75% silver nitrate, 25% potassium nitrate) were used to induce chemical cauterization on the corneas of 16 eyes. The rats were randomized to 1 of 2 groups: Group 1 (n = 8) received intraperitoneally 1 ml (4 mg/kg) trastuzumab and Group 2 (n = 8) received 1 ml saline. The corneal surface covered with neovascular vessels was measured on the photographs as the percentage of the total area of the cornea by using computer imaging analysis on the eighth day. The corneas obtained from rats were evaluated for vascular endothelial growth factor (VEGF) immunostaining semicantitatively. The number of the corneal neovascularizations were also determined on slides. The results were evaluated with the Mann-Whitney U test.
RESULTS: The burn stimulus was similar between groups. The average neovascularization area in treatment group was statistically smaller than control (P = .008). The mean VEGF staining intensity of epithelial and endothelial layers of cornea in treatment group was less than control (P = .038 and P = .041, respectively). The stroma of the treatment group showed less staining, but the difference was not significant (P = .056). The number of corneal neovascularizations on slides in trastuzumab treated eyes were less than the control group (P = .02).
CONCLUSION: Systemic administration of trastuzumab is effective in prevention of the corneal neovascularization.
PMID: 19054498 [PubMed - indexed for MEDLINE]

from the introduction of this article:
Neovascularization or angiogenesis, the formation of new blood vessels, is a normal process that accompanies tissue growth, reproduction and repair of damaged tissue during the process of wound healing.[1] But neovascularization in the eye may result in a sight-threatening condition and even blindness. A wide range of inflammatory, infectious, degenerative, or traumatic disorders may induce corneal neovascularization.[2]

A number of treatment modalities are currently used in corneal neovascularization. These include surgery, laser photocoagulation, and medication such as glucocorticosteroids, suleparoide, thalidomide, suramin, genistein, somatostatin, indomethacin, cyclosporin, methotrexate, rapamycin, and bevacizumab. [3] , [4] , [5] ,[6] , [7] , [8] , [9] , [10] , [11] , [12] , [13] , [14] , [15] There is still no clear consensus about the best treatment of corneal neovascularization.

Trastuzumab (Herceptin; Genentech, South San Francisco, California, USA), a chimeric human monoclonal antibody against the human epidermal growth factor receptor 2 (HER2) oncoprotein, is a promising agent for molecular targeting therapy against breast cancer.[16] Tumorigenesis is a multistep process and angiogenesis is critical for tumor growth and metastasis.[17] Epidermal growth factor (EGF) is known to be an angiogenic factor, and it also up-regulates expression of potent angiogenic factors, vascular endothelial growth factor (VEGF), and interleukin-8. Epidermal growth factor receptor (EGFR) activation is often linked to angiogenesis as well as to invasion and metastasis, all processes thus able to be affected by EGFR antagonists.[18] In this aspect, trastuzumab may be a multitargeted therapeutic approach in the prevention of corneal neovascularization.

The aim of this study was to investigate the effect of trastuzumab in the prevention of experimentally induced corneal neovascularization in a rat model.

[Sheila]

I am not the only one here that seems to get severe dry eye from herceptin...and the eyes tear alot trying to lubricate. Restasis has helped me immensly....it is by prescription and I got it from the eye Dr.

[bingy]

Dear Lani and Sheila,
Thanks for your responses As you well know, when something new develops, you just want to reach out. My mum is in the UK and I am in NYC so when I'm not there, my way of overcoming those miles is to do the research and forward it to my sisters. Mum is on her third year of Herceptin, she has also taken mushroom drops since her mastectomy and has done really well though she gets a very bloated belly which gets her down and prevents her from bending, though she is a real trooper and I find her laying on her side in the garden doing the weeding .Lani thanks for the uplifting info on Herceptin and prevention of blood vessels. In following that info, I think the issue is that when you get the dry eyes syndrome which seems really common among H users, the eyes are very susceptible to corneal erosion but here's a positive outcome from Moorefields Eye Hosp in the uk:
Corneal infiltration after recurrent corneal epithelial erosion.
Ionides AC, Tuft SJ, Ferguson VM, Matheson MM, Hykin PG.

Moorfields Eye Hospital, London.
Abstract
AIMS: To describe the clinical features of patients with a history of recurrent corneal epithelial erosion who develop acute corneal infiltration.

METHODS: The records were reviewed of patients who had previously been examined and treated for recurrent corneal epithelial erosion and who presented again with signs suggestive of a microbial keratitis.

RESULTS: 11 patients were described; one patient presented with similar signs on two occasions. There was typically a paracentral epithelial defect > 2 mm in diameter with an associated stromal infiltrate and an intense anterior uveitis. Three patients had a hypopyon, and four developed a subepithelial ring infiltrate. Samples were taken for microscopy and bacterial culture, with a positive isolate from two of 12 episodes (16%). Treatment with topical antibiotics and topical corticosteroid resulted in rapid re-epithelialisation and a reduction of inflammation. There was good visual outcome for all eyes, with a recurrence or symptoms of epithelial erosion in only one eye after a mean follow up period of 18 months.

CONCLUSIONS: Corneal infiltrates are an uncommon complication of recurrent corneal epithelial erosion. Despite the intensity of the infiltration the majority are culture negative using established techniques. There is typically rapid resolution and a good visual outcome, with a tendency for the episode to mark the end of further symptoms of epithelial erosion.

Many thanks for being there and many hugs,
Bingy

[StephN]

Hi -
I was on Herceptin for about 8 years. A little over 1/2 a year weekly with some chemo drugs you can see in my profile. Then went on every 3 weeks.

Due to my rising eye pressure I had a Visual Field test today and my eye doc measured the thickness of my cornea.

Turns out I have some symptoms of developing glaucoma (on my mother's side of my family), but my cornea thickness is more than average. This is a good thing in the case of possible glaucoma.

I had some dry eye annoyance while on Herceptin, but not very bad. I also have some bad pollen allergies as well as dust and animals, so don't think the Herceptin was all that at fault.

My eye doc says there are sesveral reasons for thinning cornea. Has you Mum been checked for Glaucoma?

[StephN]

P.S. Bingy - that stomach bloating is strange. I think it warrants closer checking. Not at all normal.

[Catherine]

Dry eyes at night...that is what I have. I only was on Herceptin for one year. 2 years after my Herceptin was over, I had to stop wearing my contact lens, my eyes were too dry. Now, when I wake up in the middle of the night (2-3 times) my eyes are glued shut. I have to blink and blink before I can walk to the bathroom. Same problem when I get up in the morning. If there was a fire, I would have to feel my way out of the room. (joke, but true) I keep Systane lubricant drops on my night stand. During the day my eyes are fine. For me it might be chemo, Herceptin or age.

[ElaineM]

I have had dry eyes for years, so I don't think it is totally related to the medicines I took. A nurse told me eyes can become drier and more sensitive to light during cancer treatment.
I think many factors can contribute to dry eyes. I see the eye doctor yearly and he has been prescribing drops for a long time. He told me many women get dry eyes during middle age.
I suspect allergies are part of my problem too. I am currently using Soothe XP, which can be purchased over the counter. I also use Similasan Dry Eye Relief.