Thursday, September 25, 2008

OSN discussion on blepharitis treatments

Ocular Surgery News ran an interesting discussion amongst seveal ophthalmologists about treatments for blepharitis. In some cases the differences in views about what treatments to start with is quite striking.

Physicians examine treatment options for patient with blepharitis

I was pleased to see general agreement about the importance of warm compresses... but I wonder how much attention any of them are paying to methods and ensuring their patients get compresses that are conducive to compliance.

The usual "cesspool" talk about premature insertion of plugs when there is active blepharitis.

There was some discussion about longterm use of doxy etc. Dr. Slonim compares doxycycline, minocycline and tetracycline. Clearly the frequency with which these antibiotics are prescribed has decreased since the study came out linking them to increased breast cancer risk in women, though Dr. MacDonald (whose regimen sounded like the most Rx-heavy amongst them incidentally) points out:

That study revealed an apparent relationship between oral antibiotic use and breast cancer in women; the results initially panicked everyone. You have to tell patients in advance that the one exception was the group of women on macrolide and tetracycline antibiotics for skin and dermatological/external disease conditions — there was no correlation. So you have to point that out to them in advance because your patients will find the study, and they will call you the next day about it.

Quite a range of opinions, from Dr. Slonim who routinely prescribes them to Dr. Raizman, who minimizes emphasis on drugs in general because of the chronic nature of the condition... rather, his focus is on heat and omega 3s as standard treatment:

I think just about every patient should be using hot compresses. That is easy and safe. If you see terrible meibomian gland obstruction, those patients need doxycycline, minocycline or tetracycline.

Most patients are much more mild. You start to talk to them about antibiotics, and right away they are worried about taking a chronic antibiotic therapy, and justifiably so. And now we have good data to support the use of oils taken orally that are quite helpful for the mild to moderate cases of meibomian gland disease. So I’ll have patients take flax or fish oil, about 2,000 mg a day. I do not think it is critical to focus on one particular type of oil. I think patients get benefits from using any of these products, but that would be my second line of treatment.

I like to avoid steroids. This is a chronic disease. Yes, you can clear them up temporarily. None of us want our patients on steroids for blepharitis for months or years, so I will use them for an occasional flare-up, but I like to stay away from that.

I do not find Restasis to be especially helpful. Occasionally, some patients will get benefit from it, but that is definitely low on my list of treatments, as are topical antibiotics to the lid margins. I do not find that to be as effective, either. So using that combination of strategies, more or less in that order, I get good results on the majority of my patients.

Abstract: Dry eye risks from microsurgery on tumor patients

Facial Nerve Function Insufficiency after Radiosurgery versus Microsurgery.Prog Neurol Surg. 2008;21:108-18.
Tamura M, Murata N, Hayashi M, Roche PH, RĂ©gis J.

Background: Due to the synergic role of the facial nerve and the nervus intermedius in the mechanical protection of the eye and taste, vestibular schwannomas and/or their treatment may prove to be dangerous for the visual function and taste. Our goal was to evaluate and compare the impact of the tumor itself and the impact of microsurgery (MS) or Gamma Knife radiosurgery (GKS).

Materials and Methods: A functional questionnaire evaluating, among other items, patient complaints related to the eye and taste has been given out to a series of 200 patients 3 years after the GKS of a unilateral vestibular schwannoma not previously resected. Their answers were compared with those of a group of 200 patients operated on microsurgically. A Schirmer test was additionally performed before radiosurgery (RS) and more than 2 years after RS in 66 patients.

Results: The risk of dry eye and burning eye is much higher in patients operated by MS compared to patients operated by GKS due to the high incidence of facial palsy (FP) in the former (57/99) and its absence in the later (0/80). In the population operated on microsurgically, the presence of a permanent FP (57 patients among 99 responding to the questionnaire) was, of course, associated with a high rate of complaint, with burning eye in 27 and crying eye in 39. In patients from the two arms with no FP, a dry eye was reported in 8/64 after GKS and 7/42 after MS (not significant) and a burning eye in 9/64 after GKS and 9/42 after MS (not significant). Thus, 14% of patients with no clinical signs of impairment of the VIIth motor nerve presented signs indicating the injury of the intermedius nerve, with the same probability whatever the kind of surgery. When no permanent FP was observed, a crocodile tear syndrome was more frequently observed after MS (4/42 versus 1/64; p = 0.07). This suggests an early lesion of the VIIth motor nerve and nervus intermedius and a subsequent abnormal regrowth. The only patient reporting a crocodile tear syndrome after GKS turned out to have a transiently presented mild deficit of the orbicular muscle signing a transient partial facial nerve injury. In the absence of FP, a 'crying eye' was reported more frequently after MS (16/42 vs. 9/64; p = 0.01) leading us to suspect a frequent subclinical injury of the VIIth nerve in those patients operated on using MS with no obvious FP. Patients tested with the Schirmer test before and more than 2 years later were improved in 27.3%, stable in 56.1% and worse in 16.7% of cases. The answers about taste showed that 8.1% of patients after GKS and 45.5% of patients after MS complained of taste.

Conclusions: This study is the first demonstrating that RS can induce nervus intermedius injury in a small percentage of cases (14%). These patients have been treated 11 years ago with what we can consider as 'archeo-GKS technology' compared to today's radiosurgical instruments. Influence of modern GKS on the nervus intermedius is currently under evaluation in our group. However, symptoms related to the eye and taste either due to the injury of the nervus intermedius or the VIIth motor nerve or both are much more frequent after MS than after RS.

Drug news: The latest on Prolacria

Inspire is asking the FDA for a special protocol assessment for their plans for their latest phase III trial.

Inspire initiates special protocol assessment process for dry eye trial

Sep 25, 2008 (Datamonitor via COMTEX) -- Inspire Pharmaceuticals, a biopharmaceutical company, has submitted a clinical protocol and request for special protocol assessment to the FDA for a pivotal Phase III environmental trial with Prolacria for the treatment of dry eye disease.

The protocol is based on information from a detailed analysis of the overall Prolacria clinical trial data to date, including Inspire's Phase III trials and recently completed pilot trial, and consultation with the FDA, Allergan, Inspire's corporate partner, and other dry eye experts.

After detailed analysis, Inspire determined that designing and conducting a further environmental trial was a more appropriate course than further studies of Prolacria in a controlled adverse environment.

Abstract: How the tear film thins and breaks up

Is it, or is it not evaporation... methinks this is a subject Dr. Holly has gone into at some length... Aha! Here it is. Very interesting discussion.

Contributions of evaporation and other mechanisms to tear film thinning and break-up.
Optom Vis Sci. 2008 Aug;85(8):623-30. Links
King-Smith PE, Nichols JJ, Nichols KK, Fink BA, Braun RJ.

PURPOSE: To evaluate the contribution of three mechanisms-evaporation of the tear film, inward flow of water into the corneal epithelium or contact lens, and "tangential flow" along the surface of epithelium or contact lens-to the thinning of the tear film between blinks and to tear film break-up. In addition to a discussion of relevant studies, some previously unpublished images are presented illustrating aspects of tear film break-up.

CONTRIBUTIONS OF THREE MECHANISMS TO TEAR FILM BREAK-UP: Inward flow of water into the epithelium or contact lens is probably unimportant, and a small flow in the opposite direction may actually occur. Tangential flow is probably important in certain special cases of tear film break-up-at the black line near the tear meniscus, over surface elevations, after partial blinks, and from small thick lipid spots in the tear film. In all these special cases it is argued that tangential flow is important initially, but evaporation may be needed for final thinning to break-up. It is argued that most of the observed tear film thinning between blinks is due to evaporation, rather than tangential flow, and that large "pool" break-up regions are the result of evaporation over an extended area.

CONCLUSION: Evaporation in our "free-air" conditions may be four to five times faster than the average of the values reported in the literature when air currents are prevented by preocular chambers. However, recent evaporation measurements using "ventilated chambers" give higher values, which may correspond better to free-air conditions. Thus evaporation may be fast enough to explain many cases of tear film break-up, and to give rise to considerable increases in the local osmolarity of the tear film between blinks.

Abstract: Lubricants and lenses

A little study comparing contact lens comfort after 6 hours wear if no lubricant was used, saline, or an OTC lubricating drop. Bottom line - type of lens matters more than what lubricant is used.

Lubricant effects on low Dk and silicone hydrogel lens comfort.
Optom Vis Sci. 2008 Aug;85(8):773-7.
Ozkan J, Papas E.

PURPOSE: To investigate the influence of three lubricants of varying viscosity, on postinsertion and 6 h comfort with contact lens wear.

METHODS: Comfort and associated symptoms of dryness were assessed in 15 experienced contact lens wearers. Subjects wore a low Dk lens in one eye and a silicone hydrogel in the other and participated in four separate trials involving no lubricant (baseline), saline, and two commercially available lubricants of differing viscosity. The in-eye lubricants were used immediately following lens insertion and every 2 h postinsertion for a 6 h wear period.

RESULTS: Postlens insertion comfort was significantly better for both lens types when lubricants or saline were used compared with no lubricant use. After 6 h lens wear, comfort was influenced by lens type and not by in-eye lubricant or saline use. Also after 6 h lens wear, less dryness sensation was reported for silicone hydrogel lenses when using lubricants but not saline.

DISCUSSION: Although lubricant use does help reduce dryness symptoms with silicone hydrogel lens wear, there appears to be minimal longer-term benefit to comfort. Furthermore, increased lubricant viscosity did not lead to improved longer-term comfort.

Abstract: Azasite for blepharitis

I was looking forward to seeing something in print on this after all the anecdotal reports from patients and doctors. This looks promising.

For the miracle-seekers ("Where's my magic goop?") amongst us, please note that this study did NOT explore the effects of Azasite on its own. It compared compresses only to compresses plus Azasite and found a significant improvement to results when Azasite was added. I contacted the doctor who did this study and asked him to let me know what kind of compress it was.

Efficacy of topical azithromycin ophthalmic solution 1% in the treatment of posterior blepharitis.
Adv Ther. 2008 Sep 9. [Epub ahead of print]
Luchs J.

INTRODUCTION: Azithromycin, a broad-spectrum antibiotic with potent anti-inflammatory activities, has the potential to effectively treat blepharitis, an inflammatory disease of the eyelid with abnormal eyelid flora as an etiologic determinant. The present study compared the efficacy of topical azithromycin ophthalmic solution 1% (AzaSite(R); Inspire Pharmaceuticals, Inc, NC, USA) combined with warm compresses (azithromycin group) to warm compresses alone (compress group) in patients with posterior blepharitis.

METHODS: Twenty-one patients diagnosed with posterior blepharitis were randomized in an open-label study to receive either azithromycin plus warm compresses (10 patients), or compresses alone (11 patients). All patients were instructed to apply compresses to each eye for 5-10 minutes twice daily for 14 days. Each eye in the azithromycin group also received azithromycin solution (1 drop) twice daily for the first 2 days followed by once daily for the next 12 days. Patients were evaluated at study initiation (visit 1) and at end of treatment (visit 2) for the severity of five clinical signs: eyelid debris, eyelid redness, eyelid swelling, meibomian gland (MG) plugging, and the quality of MG secretion. At visit 2, patients also rated their degree of overall symptomatic relief.

RESULTS: Twenty patients completed the study. At visit 2, patients in the azithromycin group demonstrated significant improvements in MG plugging, MG secretions, and eyelid redness as compared with the compress group. In the azithromycin group, MG plugging resolved completely in three patients and MG secretion returned to normal in two patients; no such results were seen in the compress group. Furthermore, a higher percentage of patients in the azithromycin group rated overall symptomatic relief as excellent or good. Visual acuity measurements and biomicroscopic evaluation revealed no ocular safety issues.

CONCLUSION: Azithromycin ophthalmic solution in combination with warm compresses provided a significantly greater clinical benefit than warm compresses alone in treating the signs and symptoms of posterior blepharitis.