Wednesday, June 25, 2008

Abstract: OSDI and the post-menopausal dry eye...

Aha. An opportunity to preach a sermon on a favorite topic.

As many of you know I've long been a fan of the OSDI. It's a quick 12-question survey (technically, a scientifically validated instrument) that I encourage all patients to use regularly to 'quantify' their dry eye symptoms. Complete it and take it to doctor appointments, especially if you're seeing a new doctor for the first time. Also, score yourself before and a month and three months after commencing any new treatments. If you want meaningful data, school yourself not to change your routine or treatments during that time.

Patients, if you've ever had the uncomfortable experience of trying to communicate how much pain you're in to a doctor who is looking quizzically (or worse) at you after gazing at your apparently 'quiet' corneas under a slit-lamp, the OSDI is for you. Your doctor cannot brush it aside as irrelevant. If they do, they're basically also saying that Restasis should never have been approved.

Doctors, if you've ever been tempted to think your dry eye patients who don't have glaring clinical signs are whining malcontents, I dare you to make all your patients (not just the dry eye ones) complete this survey with no explanation and then tabulate the data.

Here's a link to download a PDF copy.

Some years ago when Restasis first came on the market, Allergan reps distributed tear-off pads with this survey so doctors could use it to measure how patients are doing before and after starting on the drug. Wish they hadn't left off, but maybe we can collectively re-popularize it.

Clinical signs and symptoms in post-menopausal females with symptoms of dry eye.
Srinivasan S, Joyce E, Senchyna M, Simpson T, Jones L.
Ophthalmic Physiol Opt. 2008 Jul;28(4):365-72

Purpose: To characterize clinical signs and symptoms in a group of post-menopausal (PM) females who present with and without symptoms of dry eye.
Methods: Eighty-three healthy PM females were categorized as being symptomatic or asymptomatic of dry eye based on their response to the Allergan Ocular Surface Disease Index((c)) (OSDI) questionnaire. Non-invasive tear breakup time (NITBUT) was evaluated using the ALCON Eyemap(R). Tear volume was assessed using the phenol red thread (PRT) test and bulbar conjunctival hyperaemia was measured using objective and subjective methods.
Results: The total OSDI score (TOS) and subscores for the non-dry eye (NDE; n = 39) and dry eye (DE; n = 44) groups were significantly different (TOS: NDE = 7.43 +/- 7.71 vs DE = 24.87 +/- 13.89; p < 0.001). The DE group exhibited a shorter NITBUT (5.3 +/- 1.7 s vs 7.0 +/- 2.7 s; p = 0.0012). Tear volume was lower for the DE group (19.3 +/- 5.1 mm vs 16.3 +/- 5.6 mm; p = 0.031). Bulbar hyperaemia was higher in the DE group for both subjective grading using a modified CCLRU scale (48.4 +/- 10.0 vs 40.6 +/- 10.4; p = 0.0011) and objective measurement by spectrophotometer (Commission Internationale de l'Eclairage u' value = 0.285 +/- 0.006 vs 0.282 +/- 0.006; p = 0.005).
Conclusions: OSDI can be used to separate PM females who demonstrate clinical signs of ocular dryness. PM women with dry eye symptoms demonstrate shorter NITBUT, lower tear volume and increased bulbar conjunctival hyperaemia than those who have no symptoms.

Abstract: ELF MF and dry eye

Help! Calling electricians and engineer types with dry eye. I am ignorant as a stone about this and need a brief education.

Percolating at the back of my brain somewhere is an evolving composite answer to the question of "Why we are dry" - epidemiologically speaking. Many, probably most of the pieces are known but I am always on the lookout for additional clues. And yes, I know this study is just 15 rats for 7 days but it's suggestive and I'd like to get some sense of the potential relevance.

My question: Where do normal people typically get exposure to ELF magnetic fields?

The effect of extremely low frequency magnetic field on the conjunctiva and goblet cells.
Keklikci U, Akpolat V, Ozekinci S, Unlu K, Celik MS.
Curr Eye Res. 2008 May;33(5):441-6.

PURPOSE: The aim of this study was to examine the effects of extremely low frequency magnetic field (ELF MF) on the conjunctiva and goblet cells density.
METHODS: Thirty adult female Spraque Dawley rats were assigned to one of two groups, each containing 15 rats. The experimental group received magnetic field 4 hr/day for 7 days. The second group received standard laboratory care and served as a control. The specimens were evaluated by light microscopy for goblet cell density, conjunctival edema, inflammation, and fibroblast proliferation.
RESULTS: In ELF MF exposure group rats, the number of goblet cells was less than the control group. We also observed a significant difference between ELF MF exposure group and control group in terms of goblet cell density (p = 0.010). The ELF MF exposure group manifested conjunctival edema and inflammation compared to the control group (p < 0.001 and p = 0.003). There was no statistical difference between the groups for fibroblast proliferation (p = 0.422).
CONCLUSION: This study suggests that ELF MF exposure leads to morphological alterations of the conjunctiva and reductions in the number of goblet cells. We believe that ELF MF may cause dry eye symptoms.

Abstract: Smartplugs & canaliculitis

Maybe I'm hypersensitive because of all the people I know personally with SmartPlug complications, but if I read one more report like this I'm going to be seriously tempted to start calling them DumbPlugs.

Incidentally... I never knew that there was a "relatively large number of [Mycobacterium chelonae] infections associated with laser-assisted in situ keratomileusis and other forms of refractive surgery". Hm.

Mycobacterium chelonae canaliculitis associated with SmartPlug use.
Fowler AM, Dutton JJ, Fowler WC, Gilligan P.
Ophthal Plast Reconstr Surg. 2008 May-Jun;24(3):241-3.

Mycobacterium chelonae is ubiquitous in the environment but is an uncommon cause of ocular and periocular infections. It is a pathogen that has been gaining increased attention in the ophthalmic literature because of the relatively large number of infections associated with laser-assisted in situ keratomileusis and other forms of refractive surgery. The authors present 3 patients who developed canaliculitis culture positive for M. chelonae more than a year after SmartPlug placement. These cases highlight some of the clinical scenarios that may be encountered in those who present with canaliculitis with a history of intracanalicular plug placement. Therapeutic considerations are also suggested.

Abstract: DIabetes and dry eye

Study of dry eye signs/symptoms in diabetics.

I get kind of suspicious when I see things like "A dry eye questionnaire" (without further identification) in the Methods. Seems to me that if it were a previously published, scientifically validated instrument they would say so.

Tear Film Function in Type 2 Diabetic Patients with Retinopathy.
Yu L, Chen X, Qin G, Xie H, Lv P
Ophthalmologica. 2008 Jun 18;222(4):284-291.

Purpose: To investigate whether diabetes mellitus is correlated with tear film dysfunction.
Methods: Tear film function tests including tear film breakup time (BUT), fluorescein staining, Schirmer I test, rose Bengal staining, total tear protein detection, tear sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) and TMS-4 corneal topography were performed. A dry-eye questionnaire was used.
Results: Compared with the control group and nonproliferative diabetic retinopathy (NPDR) group, in the proliferative diabetic retinopathy (PDR) group, the BUT and the value of the Schirmer I test were reduced significantly (p < 0.01); corneal fluorescein staining scores, the positive rate of rose Bengal staining and the surface regularity index (SRI) and surface asymmetry index (SAI) were higher (p < 0.01); concentrations of lactoferrin and tear-specific prealbumin were lower (p < 0.01, p < 0.05, respectively). In diabetic patients, the SRI and SAI were positively correlated with fluorescein staining scores (r = 0.754, 0.480, p < 0.01, respectively), and the dry-eye symptoms were significantly related to an abnormal BUT and Schirmer I test (p < 0.01, respectively).
Conclusion: The declined tear film function is severer in the patients with PDR than in those with NPDR. Besides the traditional methods, tear SDS-PAGE and TMS corneal topographic indices contribute to the discovery of tear film dysfunction in diabetic patients. Copyright © 2008 S. Karger AG, Basel.

Abstract: Pipeline drug development

My main comment on this review of what's going on in drug development is:

Why have I never heard of gefarnate, and is there really any current research going on with it? I see abstracts 10 years older and more, but nothing current. Since there are other references in this abstract to dead ducks (e.g. rebamipide, which probably wasn't officially dead till after this article was complete and waiting for press) I'll assume for the moment that this is an out of date reference... unless anyone would care to enlighten me otherwise.

Incidentally, here's a link to our dry eye drug pipeline page.

Therapeutic targets in dry eye syndrome.
Peral A, Dominguez-Godinez CO, Carracedo G, Pintor J.
Drug News Perspect. 2008 Apr;21(3):166-76.

Dry eye is a multifactorial disease of the tears and the ocular surface that manifests with a wide variety of signs and symptoms. It is prevalent in about 33% of the population worldwide. Due to the importance of the pathology, new tests, drugs and technologies have been developed to assist the diagnosis, management and follow-up of the disease. Current available therapies try to alleviate symptoms and to reduce signs in order to restore the ocular surface. Depending on the etiology of the pathology it is possible to use lubricants, secretagogues, biological tear substitutes or antiinflammatory drugs, either independently or combined. Nowadays, the therapies under clinical trial are devoted to stimulating tear components (e.g., diquafosol, a P2Y receptor agonist), or mucin secretion (e.g., rebamipide, an amino acid analogue of quinolinone). Others include gefarnate, a water-insoluble terpene fatty acid that contributes to restoring mucins on the ocular surface, or cevimeline, an oral cholinergic agonist that reduces the symptoms associated with dry eye. Other potential compounds described in patents are in a lower phase of drug development. These compounds come from different families of therapies, and among others, can be found in the form of steroidal and nonsteroidal antiinflammatory agents, vitamins A and D, neurotransmitters and neuropeptides.

Journal: Musings about why we don't "get" dry eye

While trying to chase bugs and a mini-abrasion off my brain this morning I was pondering once again some of the reasons why I think good dry eye care is such a scarce commodity.

Western medicine has this annoying way of looking at things in nice neat boxes for ease of use.

Are we looking at a person, or a pair of eyes? Ophthalmology seems to want to box up the eye and isolate it from the rest of the body. Yet most of dry eye is attributable to side effects of medications and surgeries; auto-immune disease; hormones; skin disease; eyelid mechanics; unfriendly home and office environments full of dried out air and allergens; and lousy diet.

Eye surfaces and a sophisticated lubricating system, or a tear film? Similarly, the cornea folks want to box up the tear film ("Three layers... not enough oil... add oil...") and/or the ocular surface ("Inflammation Is The Enemy...Must Fight Inflammation...")

What's missing?

Well, the rest of the body, for one. We pay lip service to it by pushing fish oil supplements, or going on allergy hunts, and under certain circumstances we test for Sjogrens, and we think we've done our duty and can return to the much more comfortable business of suppressing surface inflammation medically.

Then there's the complex interworkings of the tear system. This is increasingly evident in scientific findings - the ones that bother to look for the connections. (Mess with my MGs? Guess what - my mucus will suffer too. Mess with my nerve endings? You'll screw up my aqueous production. Mess with my aqueous? You'll screw up my MGs. And on and on.)

And then there's the question of what's happening on the infamous ocular surfaces themselves. You see what you look for, which raises many interesting questions of emphasis. For example, is the problem an inadequate or imbalanced tear film - or the surface state that occurs as a result, such as the "de-wetting" or whatever it is that's causing excessive pain? But again, that idea would take us out of the medical box into another area of science altogether. Sorry, no can do!

Ponder ponder ponder. Off to start the day now.

Journal: Foreign body sensation

I woke up in the middle of the night convinced a bug had walked onto my eye.

Talk about foreign body sensation.

I couldn't feel it - not with my fingers, I mean - and I was so sleepy nothing could have dragged me out of bed to look in a mirror. Nevertheless, this idea of a bug on my cornea was on my brain the instant I woke up and I couldn't shake it. And I'm not talking spider - probably never would have felt something like that - I mean something with a nice hard scaly body that can really scratch.

My cornea hurt like heck. My drops weren't in their usual place by my bed. So, I just rubbed my eye a bit and tried to go back to sleep.

It's my left eye, normally the good one of the two. True, I wasn't wearing my usual moisture goggle or even a sleep mask. In fact I was so worn out I don't think I even put drops in last night. But I don't recall ever having any very memorable spontaneous abrasion in that eye, at least not in recent years. When I get into any serious trouble at night it's always my right eye that gets the worst of it.

When I finally got up, sure enough, the eye was a nice shade of pink and had lots of mucous strands as though it had been trying to push something out. I hunted around and couldn't find any sign of something in my eye, so if there ever was something there, I guess it got away. It's been awhile since I had that strong an FBS right in the middle of my cornea. I've been back to the mirror several times to see if I could find anything, you know, like a tiny little leg or something. Nope, nothing. I've been pouring in the Dwelle, and the pain's starting to go down at least. And the way I noticed that is about the time I started becoming aware of how much my right eye hurts. Nothing like one kind of pain out-shouting another.

Teacher, I need a blackboard to go write on...

I will take care of my eyes before bed.
I will take care of my eyes before bed.
I will take care of my eyes before bed.