Tuesday, February 5, 2008

Study: Sjogrens + LASIK = ...

This one is definitely going to resonate with some of our Dry Eye Talk crowd - particularly those who suffered severe dry eye after LASIK and not too longer afterwards were diagnosed with Sjogrens. Bearing in mind that the average time to diagnosis of Sjogrens is something like 10 years, these case reports should be quite sobering - and should also raise serious questions about the views propounded in a memorable editorial in one of the major refractive surgery journals a couple of years ago supporting the relative safety of LASIK in Sjogrens patients.

Incidentally, to the general public, the title of this study sounds rather misleading. I think of "Aggravated dry eye" as meaning... I was dry and you made me worse. That's not the case here.

Aggravated Dry Eye After Laser In Situ Keratomileusis in Patients With Sjögren Syndrome.
Liang L, Zhang M, Zou W, Liu Z.
Cornea. 2008 Jan;27(1):120-123

PURPOSE:: To report 2 patients with Sjögren syndrome (SS) who had no or mild dry eye symptoms preoperatively but developed severe and refractory dry eye after laser in situ keratomileusis (LASIK). METHODS:: Two women with well-controlled early-stage SS developed severe dry eye, punctate epithelial keratopathy, and refractive regression 15 and 2 months after LASIK. Both patients were treated with punctal occlusions, artificial tears, fluorometholone 0.02% eyedrops, autologous serum, and systemic immunosuppressants. RESULTS:: Ten months after treatment, both patients exhibited only minor improvements in dry eye symptoms on the basis of changes in Schirmer test results, corneal fluorescein staining, and refractive errors, whereas their tear breakup time and corneal sensation remained unchanged. CONCLUSIONS:: Severe and refractory dry eye can develop after LASIK in patients with preexisting well-controlled early-stage SS.

Study: Restasis vs. Refresh Plus

Well, DUH.

CONCLUSIONS:: Cyclosporine emulsion, but not artificial tears, increases goblet cell density and production of the immunoregulatory factor TGF-beta2 in the bulbar conjunctiva in patients with dry eye.

Translation, in the context of this specific study:

"Restasis might help clinical features of some kinds of dry eye but Refresh Plus doesn't."

Or maybe:

"The drug for which the co-pay alone could buy you six boxes of useless preservative free artificial tears does more than said tears."

No offense whatsoever to the illustrious editors of Cornea, for whom and for which I have unbounded respect, but show me a published peer-reviewed study suggesting a $10 product is as effective as, or more effective than, the blockbuster ophthalmic drug of the decade and I'll...

Hey, wait a minute! Why are they comparing Restasis to Refresh Plus? Are doctors out there complaining that Restasis doesn't work any better than artificial tears, so somebody had to go and prove them wrong? Hmph. Sacrilege!

Oh, you want the whole thing? Here:

Effects of Sequential Artificial Tear and Cyclosporine Emulsion Therapy on Conjunctival Goblet Cell Density and Transforming Growth Factor-beta2 Production.
Pflugfelder SC, De Paiva CS, Villarreal AL, Stern ME
Cornea. 2008 Jan;27(1):64-69.

PURPOSE:: To evaluate the effects of sequential treatment with artificial tears and cyclosporine emulsion on conjunctival goblet cell density and production of transforming growth factor (TGF)-beta2 in patients with dry eye disease. METHODS:: Patients with dry eye disease (N = 6) defined by an Ocular Surface Disease Index symptom score >/=25, Schirmer test 1 <10 mm, and corneal fluorescein and conjunctival lissamine green staining scores >/=3 were treated with artificial tears (Refresh Plus; Allergan, Irvine, CA) 4 times a day for 4 weeks, followed by 0.05% cyclosporine emulsion (Restasis; Allergan) twice a day for 12 weeks. Impression cytology was performed on the bulbar conjunctiva of both eyes at baseline, after artificial tear therapy, and after 6 and 12 weeks of cyclosporine therapy. Goblet cells were counted in 5 representative microscopic fields per membrane in those taken from the temporal and inferior bulbar conjunctiva of the worse eye, and membranes taken from the fellow eye were immunostained for TGF-beta2. RESULTS:: There were no differences in mean goblet cell density between baseline and 4 weeks of artificial tears in the temporal and inferior bulbar specimens. After 6 weeks of cyclosporine emulsion, goblet cell density was significantly greater than baseline and artificial tears in the inferior bulbar conjunctiva (P < 0.01). After 12 weeks of cyclosporine emulsion, goblet cell density was significantly greater than baseline and artificial tears in both temporal and inferior bulbar sites (P < 0.01). The number of TGF-beta2-positive goblet cells was also noted to increase after 6 and 12 weeks of cyclosporine therapy (P < 0.001). CONCLUSIONS:: Cyclosporine emulsion, but not artificial tears, increases goblet cell density and production of the immunoregulatory factor TGF-beta2 in the bulbar conjunctiva in patients with dry eye.

Study: Lotemax and dry eye

The obligatory peer-reviewed study to support Lotemax for ocular surface inflammation (read, dry eye), or better yet the popular Lotemax + Restasis cocktail. Yawn.

Treatment of Ocular Inflammatory Conditions With Loteprednol Etabonate.
Pavesio CE, Decory HH Phd.
Br J Ophthalmol. 2008 Feb 1

Ocular inflammatory diseases impose a significant medical and economic burden on society. Corticosteroids are potent anti-inflammatory agents that have been used successfully to treat ocular inflammation. Topical corticosteroids provide maximal drug delivery, and are used to reduce the signs and symptoms of intraocular and ocular surface inflammation. However, side effects associated with topical corticosteroids--including increased intraocular pressure (IOP), risk of cataract formation after long-term use, and decreased resistance to infection--are concerns. Loteprednol etabonate (LE) is an ester corticosteroid with a high therapeutic index that contains an ester, rather than a ketone, at carbon-20 of the prednisolone core structure. LE blocks the release and action of inflammatory mediators and is clinically effective in the treatment of steroid-responsive inflammatory conditions including giant papillary conjunctivitis, seasonal (intermittent) allergic conjunctivitis, and uveitis. LE relieves ocular surface and lacrimal gland inflammation associated with dry eye and is used in combination with cyclosporine A as a treatment of dry eye. LE is also effective in the treatment of postoperative ocular inflammation. Because of its rapid de-esterification to inactive metabolites, LE appears to have an improved safety profile compared to ketone corticosteroids, and may be more suitable than ketone corticosteroids for the treatment for ocular inflammatory conditions in which long-term therapy is necessary. However, further comparative safety studies are needed.

Misc: OH the irony

In Safari, I have to keep my pop-up blocker turned off because of some company software I use that just won't work right if I have the pop-up blocker on.

So, about ten times a day, I am getting this icy light blue & white square in the middle of my screen brazenly stating:

It's not just LASIK.

Of all the trash that could be popping up on my screen, why have I of all people been blessed with the LASIK ads? I ask you.

Study: Some artificial tears more than palliative?

This little tidbit in Experimental Eye Research suggests some doctors are thinking some OTC drops could actually be therapeutic, and they're proposing a theory of how they might be promoting eye surface healing. Hm. I don't know about the theory, but I sure find the highlighted parts of the abstract appealing; to which I'll add: AND OTC!! When the patient can't afford the co-pay, compliance sure takes a dive don't it.

Activation of the epidermal growth factor receptor by hydrogels in artificial tears.
Lozano JS, Chay EY, Healey J, Sullenberger R, Klarlund JK.
Exp Eye Res. 2007 Dec 23

Most formulations of artificial tears include high-molecular weight hydrophilic polymers (hydrogels) that are usually thought to serve to enhance viscosity and to act as demulcents. A few reports have indicated that application of some of the polymers accelerates healing of wounds in epithelia. Since activation of the epidermal growth factor (EGF) receptor is critical for spontaneous corneal epithelial wound healing, we tested commonly used hydrogels for their ability to activate the EGF receptor and enhance closure of wounds. Five structurally unrelated hydrogels used in artificial tears were found to activate the EGF receptor. Importantly, two of the hydrogels enhanced wound healing in an organ culture model. We propose that the efficacy of hydrogels in treating dry eye may be related to their ability to activate the EGF receptor, and that hydrogels are inexpensive, safe agents to promote healing of wounds in the cornea and possibly in other tissues.

Rebecca's journal: My first tentative new Omega 3 step...

I see no reason not to come right out and admit it.

When faced with it personally, I found the idea of consuming flaxseed oil completely revolting.

Never mind that I know plenty of perfectly reasonable people who do this regularly.

Never mind that I know it's better for you than the capsules.

Never mind even that I've been guiltily doling out hypocritical advice about it to others for years. "You know, you can take capsules, but it's better to get it in liquid form... You can mix it with a salad dressing, or blend it into a smoothie...." (Or so I've heard, snicker.) That's for other people. For heaven's sake, I'm married to a Greek; you can't expect me to insult our beloved extra virgin olive oils by putting that stuff on my salad. Smoothie? Sorry but I've never bothered to replace our blender since we moved.

Yes, I'm one of those ignorant, pitiful wimps that really have never dared to venture beyond capsules in their Omega 3 quests. There is something about that dreaded tablespoon of flaxseed oil that conjures up visions of cod liver oil or something. Not that I ever actually consumed any of that either, but I read about kids that had to.

The beginning of the end, though I didn't know it at the time, came when Debra Schaumberg of Harvard, who's been rather prominent in some dry eye reseasrch, passed by my booth at ASCRS (an ophthalmology conference where I was exhibiting for The Dry Eye Shop) last spring in San Diego. I asked what she recommends in terms of Omega 3s for dry eye. She said flatly, "Barleans liquid flaxseed oil. Period. You don't need anything else." and walked on.

Many months later when I found myself at Barleans farm in Ferndale, Washington, Bruce Barlean pretty much finished up the process of persuading me to at least give it a try. In fact, considering that to date I have purchased exclusively capsules from Barleans, and further considering that those capsules are more costly and less efficient (from a user standpoint) than the liquid form, I was quite amused to find that Bruce seems to feel the same way about his liquid oil compared to capsules approximately the same way I feel about my rice baggy compared to warm washcloths for MGD.

So, here is what my first tentative foray into the world of imbibing Barleans fresh pressed flaxseed oil looked like:

Among the loot I brought home from Barleans, I managed to snag a bottle of cinnamon flavored oil. I had no idea what I was going to do with it; I'm not even that fond of cinnamon per se. But it just sounded a little less daunting than the elite high lignan flaxseed oil.

Now, everyone has always said you should mix flaxseed oil with yoghurt. So I spooned plenty of my favorite yoghurt (Nancy's organic lowfat) into a bowl. It brought back memories of a certain period during my childhood when my mother felt it was her duty to attempt to feed liver to her eight children once a month. Among our many ruses (mind, we had no convenient dog, and the curtains were too far from the table) was heaping mashed potatoes on the plate, burying the liver and deciding we were just unbearably full when there was a small pile of mashed potatoes left. Unfortunately, oil isn't solid.

I steeled myself, grabbed the bottle, and squirted some oil on top of the yoghurt.

Gawd, what a color.

The charitable term would, I think, be saffron. It reminded me of what you see in the... never mind, when you're taking a B complex vitamin. I'm supposed to EAT this stuff? You can't be serious.

Sigh. I started stirring, and finally got it all mixed in to the point you couldn't see any of it. Dumped some berries on top. And started eating.

Oh my goodness. YUM. There's a slight cinnamony taste to my yoghurt and berries. You mean that's IT?


Heck, I can DO this. Handed it to my other half. He likes it! Hey Mikey! His recent cholesterol numbers alone are more than enough motivation to keep me faithfully serving this for breakfast, never mind the dry eyes and the dry eye shop product testing nonsense.

Thankfully, we are both people of routine and have absolutely no desire for breakfast variety. This is now our daily morning routine. My first 12 oz bottle is already getting low. I ordered some more, along with the rest of the liquid flaxseed oils, today, and I'm almost begrudging having to share it with the shop when it comes.

And guess what: Barleans have promised me some little sample bottles!! They are cute as a button and a great way to give it a whirl without buying one of those intimidating whole bottles. Look for the first set in the shop no later than the 25th. I'll have the cinnamon plus the lemonade, the standard flaxseed oil and the famous high lignan flaxseeed oil.

I shall report back when I have anything new to say about my growing acquaintance with flaxseed oil....