Thursday, February 7, 2013

And now, at last

I've got my blog caught up all the way to... seven days ago! 

And I've only ignored 12 phone calls in the process! If yours was one or more of them, do forgive me!

I'm going to go indulge my favorite self-reward (see below) for a moment, then I'll start trying to catch up on the calls. 

Ever feel like a gerbil on the wheel?

Abstract: And, a brief word from developing diagnostics...

A fluorescent probe was used to identify mucin depleted areas on the ocular surface and test the hypothesis that tear lipocalin retrieves lipids from the eyes of normal and dry eye subjects.
 METHODS. Fluorescein labeled octadecyl ester, FODE, was characterized by mass spectrometry and absorbance spectrophotometry. The use of FODE to define mucin defects was studied with impression membranes under conditions that selectively deplete mucin. The kinetics of FODE removal from the ocular surface was analyzed by sampling tears from control and dry eye patients at various times. The tear protein-FODE complexes were isolated by gel filtration and ion exchange chromatographies, monitored with absorption and fluorescent spectroscopies and analyzed by gel electrophoresis. Immunoprecipitation verified FODE complexed to tear lipocalin in tears.
FODE exhibits an isosbestic point at 473nm, pKa of 7.5, and red shift relative to fluorescein. The low solubility of FODE in buffer is enhanced with 1% Tween 80 and ethanol. FODE adheres to the ocular surface of dry eye patients. FODE produces visible staining at the contact sites of membranes, which correlates with removal of mucin. Despite the fact that tear lipocalin is reduced in dry eye patients, FODE removal follows similar rapid exponential decay functions for all subjects. FODE is bound to tear lipocalin in tears.
Tear lipocalin retrieves lipid rapidly from the human ocular surface in mild to moderate dry eye disease and controls. With improvements in solubility, FODE may have potential as a fluorescent probe to identify mucin depleted areas.
 Invest Ophthalmol Vis Sci. 2013 Jan 29. pii: iovs.12-10817v1. doi: 10.1167/iovs.12-10817. [Epub ahead of print]
Yeh PTCasey RGlasgow BJ.
Departments of Ophthalmology, Pathology and Laboratory Medicine, David Geffen School of Medicine at UCLA, Jules Stein Eye Institute, Los Angeles, CA, United States.

Abstract: Refining the hypotheses of dry eye....

Dry eye as a mucosal autoimmune disease.

Dry eye is a common ocular surface inflammatory disease that significantly affects quality of life. Dysfunction of the lacrimal function unit (LFU) alters tear composition and breaks ocular surface homeostasis, facilitating chronic inflammation and tissue damage. Accordingly, the most effective treatments to date are geared towards reducing inflammation and restoring normal tear film. The pathogenic role of CD4+ T cells is well known, and the field is rapidly realizing the complexity of other innate and adaptive immune factors involved in the development and progression of disease. The data support the hypothesis that dry eye is a localized autoimmune disease originating from an imbalance in the protective immunoregulatory and proinflammatory pathways of the ocular surface.

Int Rev Immunol. 2013;32(1):19-41. doi: 10.3109/08830185.2012.748052.
Stern MESchaumburg CSPflugfelder SC.
Biological Sciences, Inflammation Research Program, Allergan Inc. , Irvine, CA , USA.

Abstract: Come ON, docs, that baby shampoo is soooo 1990s!

This "baby" shoulda been put to bed a long, long time ago.

Really, we ought to take a clue from the label itself: "No More Tears". As if we don't need all we can get!

Baby shampoo is not only a poor tool for the job of lid hygiene compared to the MANY other things available specifically for the purpose, but it's also irritating to the eyes of a great many of us.

Blepharitis due to Meibom gland dysfunction (MGD) is presumed to be one of the main reasons for dry eye symptoms which occur in up to 50% of contact lens users. Thus, MGD presumably plays an important role in dry eye in contact lens wearers. In the present prospective, randomized and double blind trial the efficacy of two established treatment options for MGD and blepharitis was evaluated in symptomatic contact lens wearers.
In this prospective, randomized 2-centre trial 53 symptomatic contact lens wearers suffering from blepharitis were included. Patients were randomly selected for two treatment groups: group A performed lid margin hygiene using the commonly recommended mild baby shampoo (Bübchen Kinder Shampoo-extra augenmild, Bübchen Werk Ewald Hermes Pharmazeutische Fabrik GmbH, Soest, Germany) and group B performed lid margin hygiene using a phospholipid-liposome solution specially designed for lid hygiene (Blepha Cura, Optima, Moosburg/Wang, Germany), each for 4 weeks. Before as well as 4 weeks after initiation of this study the following tests were performed: standardized subjective assessment using the ocular surface disease index, non-invasive break-up time (NIBUT) and objective evaluation of lid-parallel conjunctival folds (LIPCOF) and further lid margin criteria by double blinded evaluation of slit lamp photographs.
Of the 53 symptomatic contact lens wearers suffering from blepharitis 21 (39,6%) were randomly selected for treatment group A and 32 (60.4%) for group B. In both treatment groups there was objective and subjective improvement of symptoms of dry eye in contact lens wearers. Interestingly, there was a significantly greater improvement, subjective as well as objective, in treatment group B which used the phospholipidliposome solution for lid margin hygiene compared to group A using baby shampoo.
Although both therapies improved symptoms of dry eye due to blepharitis in symptomatic contact lens wearers, patients using phospholipid-liposomal solution for lid margin hygiene demonstrated a significantly greater clinical benefit from the therapy. Thus, clinical practice recommending just baby shampoo for lid margin hygiene should be re-considered, as phospholipid-liposomal solution for lid margin hygiene appears to yield greater and faster clinical benefits for symptomatic contact lens wearers suffering from dry eye symptoms.

Ophthalmologe. 2013 Jan 27. [Epub ahead of print]
[Article in German]
Khaireddin R.
Augenarzt im JosefCarrée Bochum, St.Josef-Hospital,Universitätsklinikum der Ruhruniversität Bochum, Gudrunstr. 56, 44791, Bochum, Deutschland, 

Conjunctivochalasis vs dry eye

Little newsclip from Hawaiian Eye 2013 caught my eye:

By all means, let's talk about conjunctival chalasis and the overlap of symptoms it can have with dry eye...

WAIKOLOA, Hawaii — Recognizing conjunctival chalasis depends on listening to the patient’s symptoms and investigating any report of a specific site of discomfort or foreign body sensation, a speaker said.
Conjunctival chalasis occurs when there is a degeneration of Tenon’s fascia that ordinarily tethers the bulbar conjunctiva to the globe,” OSN Cataract Surgery Section Editor John A. Hovanesian, MD, FACS, said at Hawaiian Eye 2013. “This allows stretching and redundancy of the conjunctiva, which bunches up at the inferior lid margin, and sometimes elsewhere, and causes a foreign body sensation especially when the patient blinks.”
Conjunctival chalasis, which is a common and frequently misdiagnosed condition that mimics dry eye, is accompanied by signs of conjunctival redundancy.
Hovanesian recommends performing a “thumb test,” wherein the clinician, pressing gently on the lower lid externally over the area of discomfort, puts light pressure against the globe and asks the patient to move the eye back and forth in a direction that would deliberately cause gathering of the bulbar conjunctiva and pinching between the globe and the eyelid margin.
“When the patient complains of a specific site of pain, and there is evidence of conjunctival laxity, and there is a positive ‘thumb test,’ you’ve got your diagnosis of conjunctival chalasis,” Hovanesian said.
Fair enough. Getting a detailed thorough diagnosis is really, really important in any ocular surface disease, especially when there's a lot of chronic pain going on.

Which then leads us to the inevitable dilemma about treatment. Do we slice & dice?

After making an attempt at lubrication with artificial tears, Hovanesian recommends surgical excision with ocular surface reconstruction with amniotic membrane. The technique is highlighted on his website at

This is where I start getting worried... having come across far too many people over the years who had high ocular surface pain levels and were highly motivated to pursue any and all treatment. They had ocular surface reconstruction with amniotic membrane, and they felt and looked great... for six months. At some point later, back to square one. Maybe $10k poorer.

Often these people have had a slightly different diagnosis from every doctor they went to. No one was ever really able to help then. Suddenly, an exciting and totally different diagnosis! Better yet, I can fix you! One little surgery and all that will be gone!

How do you not succumb?

Caution, folks, caution. Fine, suppose we've established your conj is a mess BUT have we established, do we have sufficient reason to believe that's what's your pain source or even tipping point is? Really?

Naturally, my views will be biased because I hear far more from unhappy patients than happy patients (nature of the beast). Nevertheless, I think my concern is valid. It's so tempting for a doctor when they see a nail that looks like a great match for their hammer, to hammer away. But whenever we're talking about ocular surface pain, you've got to appreciate how little is really known about corneal pain, and not set patients up to expect miracle cures when at the end of the day we don't really know.

Abstract: Contamination of standard serum eye drop containers

Eek. 28.9% contamination rate for standard autologous serum containers after just 7 days of treatment.

Autologous serum users take note, re the difference special filters made in keeping serum drop containers from getting contaminated. I have no idea what the cost implications are, but this might be a nice study to copy and talk over with your doctor.

To assess the effect of the use of containers with an adapted sterilizing filter on the contamination of autologous serum eyedrops.
Prospective, consecutive, comparative, and randomized study.
Thirty patients with Sjögren syndrome.
One hundred seventy-six autologous serum containers used in home therapy were studied; 48 of them included an adapted filter (Hyabak; Thea, Clermont-Ferrand, France), and the other 128 were conventional containers. Containers equipped with a filter were tested at 7, 14, 21, and 28 days of use, whereas conventional containers were studied after 7 days of use. In addition, testing for contamination was carried out in 14 conventional containers used during in-patient therapy every week for 4 weeks. In all cases, the preparation of the autologous serum was similar. Blood agar and chocolate agar were used as regular culture media for the microbiologic studies, whereas Sabouraud agar with chloramphenicol was the medium for fungal studies.
Microbiologic contamination of containers with autologous serum eyedrops.
Only one of the containers with an adapted sterilizing filter (2.1%) became contaminated with Staphylococcus epidermidis after 1 month of treatment, whereas the contamination rate among conventional containers reached 28.9% after 7 days of treatment. The most frequent germs found in the samples were coagulase-negative Staphylococcus (48.6%). With regard the containers used in the in-patient setting, 2 (14.3%) became contaminated after 2 weeks, 5 (35.7%) became contaminated after 3 weeks, and 5 (50%) became contaminated after 4 weeks, leaving 7 (50%) that did not become contaminated after 1 month of treatment.
Using containers with an adapted filter significantly reduces the contamination rates in autologous serum eyedrops, thus extending the use of such container by the patients for up to 4 weeks with virtually no contamination risks.
Ophthalmology. 2012 Nov;119(11):2225-30. doi: 10.1016/j.ophtha.2012.06.028. Epub 2012 Aug 4.
López-García JSGarcía-Lozano I.
Ophthalmology Service, Hospital Cruz Roja, Madrid, Spain.

Abstract: Ah me, the complexity of it all

Here's another one of those abstracts that underscores why dry eye disease can be such a difficult and baffling disease to try to understand and treat. 

They just took a bunch of people and evaluated them in great detail now and 6 weeks into treatment and had a look at how their clinical signs changed versus how their symptoms changed. 

To evaluate changes in symptoms, objective tests, and signs after medical treatment of subjects with evaporative-type dry eye disease (EDE) caused by Meibomian gland dysfunction (MGD), and to analyze correlations among symptoms, signs and test results in the worse eyes (W-eyes) of the subjects.
Prospective clinical study of 21 symptomatic subjects with EDE caused by MGD. Subjects who were diagnosed with EDE in a first visit were treated for 6 weeks and re-evaluated in a second visit. The differences between initial and second visits were evaluated. Correlations among clinical symptoms, signs, and test results were performed using the data of the W-eyes. Variables evaluated included: dry eye symptoms, best corrected visual acuity (BCVA), contrast sensitivity, conjunctival hyperemia, phenol red thread test, tear break-up time (TBUT), tear meniscus height (TMH), corneal fluorescein and conjunctival rose Bengal staining, tear lysozyme concentration, Schirmer test, and lid margin assessment.
All items evaluated improved after treatment, but only conjunctival hyperemia and TMH improved significantly. TBUT and lid margin changes improved, but still remained abnormal. There were significant correlations among symptoms questionnaires and some clinical tests (TBUT, conjunctival hyperemia, TMH, and conjunctival rose Bengal staining).
Despite the instability of the tear film and lid margin alterations that continued after treatment, subjects with MGD improved symptomatically. The low degree of correlations among W-eye signs, symptoms, and tests reflects the independency of symptoms and signs in this complex pathology.

Curr Eye Res. 2012 Oct;37(10):855-63. doi: 10.3109/02713683.2012.683508. Epub 2012 May 25.
Cuevas M, González-García MJ, Castellanos E, Quispaya R, Parra Pde L, Fernández I, Calonge M.
Ocular Surface Group, Institute of Applied OpthalmoBiology (IOBA), University of Valladolid, Valladolid, Spain.

Abstract: Inflammatory dry eye and rheumatoid arthritis

The purpose of this research was to study ocular surface inflammation in relation to systemic disease activity in rheumatoid arthritis (RA) patients with or without secondary Sjögren's syndrome (SSII and non-SSII respectively). The study was conducted in two phases. In phase I, 12 patients with active RA SSII and 12 with active RA non-SSII were consecutively enrolled. Each completed an Ocular Surface Disease Index (OSDI) questionnaire and underwent a full eye exam and in vivo confocal microscopy examination of the cornea. Tear fluid samples were collected in sponges and analyzed for IL-1α, -6, and -8, and TNF-α. When RA activity was suppressed by systemic treatment the patients entered phase II of the study in which all of the phase I examinations were repeated. In RA SSII patients, OSDI, fluorescein staining dendritic cell density, and concentrations of IL-1α and IL-6 decreased significantly (P < 0.01) between phases I and II. Tear breakup time scores increased significantly. For RA non-SSII patients, there were no significant differences between phases I and II. Differences in the clinical, cellular and cytokine responsiveness to systemic RA treatments show that the ocular surface pathology is dissimilar for RA SSII and RA non-SSII patients.

Innate Immun. 2013 Jan 22. [Epub ahead of print]
Villani EGalimberti DDel Papa NNucci PRatiglia R.
University of Milan, Milan, Italy.

Wednesday, February 6, 2013

Abstract: OMGD, AKA MRKC (LOL)

Do you remember when the term "Non Obvious MGD" emerged?

Well, here's a new term for its counterpart. Dr. Suzuki of Kyoto Pref. U. has coined the elegant, dignified term Meibomitis Related KeratoConjunctivitis (MRKC). Though personally I'd prefer to stick with what I've always used: Obvious MGD. Kind of a nice ring to it, wouldn't you say?

I can just hear the conversations now.

"Well," (snickers the patient during a visit to his fifth ophthalmologist) "I guess my first doctor was right all along. I really do have NO MGD."

"Oh my God" (exclaims the optometry student) "Just look at that OMGD!"

Et cetera.

Meibomian gland inflammation, "meibomitis," is associated with ocular surface inflammatory diseases. However, these diseases are poorly defined clinically, making effective treatment difficult. Herein, we propose a new disease subset, termed meibomitis-related keratoconjunctivitis (MRKC). The ocular surface features of MRKC include: meibomitis with redness and swelling of the eyelid margin and palpebral conjunctiva; superficial vascularization and granulomatous nodules in the cornea; and conjunctival hyperemia, similar or identical to that observed in phlyctenular keratitis. The characteristics of MRKC patients include a significantly higher prevalence in women, multiple history of chalazia, close association with meibomitis, the presence of specific human leukocyte antigen association, high Propionibacterium acnes detection rates in meibum culture, and the effectiveness of systemic antimicrobial therapy targeting P. acnes. MRKC may share many clinical features with ocular rosacea, especially during childhood. The clinical effectiveness of systemic antimicrobial agents in treating both diseases suggests the importance of focusing on the elimination of bacteria such as P. acnes.

Cornea. 2012 Nov;31 Suppl 1:S41-4. doi: 10.1097/ICO.0b013e31826a04dd.
Suzuki T.
Department of Ophthalmology, Kyoto Prefectural University of Medicine, Kyoto, Japan.

Abstract: Glaucoma and dry eye - incidence & risk factors

30 to 40+ % is pretty staggering when you think about it. It ought to be far more than sufficient to induce glaucoma doctors and general ophthalmologists to sit up and pay more attention to what they're prescribing to their glaucoma and ocular hypertension patients.

Risk factors to develop ocular surface disease 
in treated glaucoma or ocular hypertension patients.

To identify risk factors for developing ocular surface disease (OSD), to verify the prevalence of OSD, and to record efficacy of questionnaires in identifying symptoms' impact on patients' quality of life.
This was an observational, cross-sectional study of patients with topically treated glaucoma. Tear film break-up time (TFBUT) and punctate keratitis were evaluated; 2 quality-of-life questionnaires (National Eye Institute-Visual Function Questionnaire 25 and Glaucoma Symptom Scale) were submitted to all patients. Class of previous and current intraocular pressure (IOP)-lowering drugs, number of drugs, number of drops/day, and total and current benzalkonium chloride (BAK) exposure were collected.
A total of 233 patients completed the study. TFBUT was abnormal in 71 (30.5%) eyes; punctate keratitis was present in 74 (31.7%). Keratitis was more frequent with increasing number of eyedrops (p = 0.008) and number of instillations per day (p = 0.009). Ocular surface disease was present in 97 (41.6%) patients and was statistically related to number of medications used (p = 0.026). The univariate analysis pointed out that patients with OSD were older (p = 0.04), had lower IOP values (p = 0.03), were topically treated for more time (p < 0.0001), had assumed more BAK (p < 0.0001), and presented worst quality of life (p < 0.01). The multivariate analysis found that OSD was related to number of medications used (p = 0.002), prolonged use of preserved medications (p = 0.005), and total BAK exposure  (p < 0.001).
There is clinical evidence that the number of medications, their prolonged use, and the total BAK exposure are risk factors to develop OSD in patients with glaucoma. To prevent OSD onset, BAK exposure and the number of topical medications should be reduced.

Eur J Ophthalmol. 2012 Dec 17:0. doi: 10.5301/ejo.5000220. [Epub ahead of print]
Rossi GC, Pasinetti GM, Scudeller L, Raimondi M, Lanteri S, Bianchi PE.
University Eye Clinic, Fondazione IRCCS Policlinico S. Matteo, Pavia - Italy.

Abstract: Restasis for radiation-induced dry eye in kids

3 out of 8. 27.3% success rate. 

I just had a flashback.... Some company selling fruit drinks, I'm thinking in the 1980s? Rather conventional happy family ads playing up the amazing fact that they had 10% fruit juice in their drink! (Gosh!) 

So some company selling unadulterated fruit juice seizes the opportunity and runs a series of commercial spoofs on the 10% theme, like a teen boy rushing home and enthusiastically telling his parents, "I got 10% right on my math test!"

Perspectives, perspectives. 

On the other hand, in the world of complex disease it's not all about the numbers. It's about something helping someone somewhere. Bet the three kids in this study, and their folks, were grateful something did.

Sadly, the FDA, and simple drug world economics (or do I mean corporate greed?) have to have compelling numbers. So things that work for some people (and obviously I'm not talking about Restasis which, although it, yes, works 'for some people', has been a blockbuster drug for a long time) never make it to market at all. 

Dry eye disease is a well-known late complication of radiation therapy and is often difficult to treat. We evaluated the usefulness of cyclosporine 0.05% ophthalmic emulsion for the treatment of radiation-associated dry eye in children. Eleven children received cyclosporine 0.05% emulsion twice daily after failure of conventional therapy. After 6 months, dry eye manifestations improved in three children (27.3%). The remaining eight children showed no improvement with cyclosporine 0.05% ophthalmic emulsion. These results suggest that twice-daily cyclosporine 0.05% ophthalmic emulsion has limited use in children with refractory radiation-associated chronic dry eye. Pediatr Blood Cancer © 2013 Wiley Periodicals, Inc.

Pediatr Blood Cancer. 2013 Jan 17. doi: 10.1002/pbc.24461. [Epub ahead of print]
Hoehn ME, Kelly SR, Wilson MW, Walton RC.
Department of Ophthalmology, Hamilton Eye Institute, University of Tennessee College of Medicine, Memphis, Tennessee; Division of Ophthalmology, St. Jude Children's Research Hospital, Memphis, Tennessee.

Abstract: Dry eye after blepharoplasty

Excellent piece looks in more detail at how many people have dry eye symptoms after blepharoplasty and, oh so importantly, WHO does, helping pin down risk factors both in terms of patient characteristics before surgery and which specific surgeries caused more dry eye. Thank you, thank you Dr. Prischmann et al.

ONE QUARTER of blepharoplasty patients reported dry eye symptoms, and it's not just about postoperative lagophthalmos. Read on....

To determine the incidence of and risk factors associated with dry eye symptoms (DES) and chemosis following upper or lower blepharoplasty. To examine the outcomes among long-term blepharoplasty data to better understand the incidence of and risk factors associated with dry eye symptoms (DES) and chemosis, to evaluate the known risk factors for DES in the general population, and to analyze intraoperative procedures (such as forehead-lift, midface-lift, canthopexy, and canthoplasty) to determine their effects on DES and chemosis.
A retrospective medical record review was performed among all the cases of upper or lower blepharoplasty performed by the senior author during a 10-year period (January 1999 through December 2009). A self-reported dry eye questionnaire was used to collect baseline and follow-up data. Patients with incomplete medical records, multiple (>1) revision procedures, less than 3 weeks of postoperative follow-up data, or a history of Sjögren syndrome, severe thyroid eye disease, histoplasmosis ocular infection, periocular trauma causing eyelid malposition, or radiotherapy for nasopharyngeal cancer were excluded from the study. Binary logistic regression analyses were performed to analyze the relationship between 13 preoperative and anatomical variables and DES or chemosis. χ2 Tests were performed to analyze the relationship between intraoperative risk factors and DES or chemosis.
In total, 892 cases met the study inclusion criteria. Dry eye symptoms and chemosis following blepharoplasty were reported in 26.5% and 26.3% of patients, respectively. The incidences of DES and chemosis were significantly higher in patients who underwent concurrent upper and lower blepharoplasty (P < .001) and in patients who underwent skin-muscle flap blepharoplasty (P = .001). Hormone therapy use and preoperative scleral show were associated with DES after blepharoplasty (P < .05). Male sex, preoperative eyelid laxity, and preoperative DES were associated with an increased incidence of chemosis following blepharoplasty (P < .05). Intraoperative canthopexy significantly increased the risk for developing chemosis (P = .009), and postoperative lagophthalmos significantly increased the risk for DES following blepharoplasty (P < .001).
Dry eye symptoms and chemosis are common following blepharoplasty, and the risk for developing these conditions may increase with intraoperative canthopexy, postoperative temporary lagophthalmos, concurrent upper and lower blepharoplasty, and transcutaneous approaches violating the orbicularis oculi muscle. Patients with a preoperative history of DES, eyelid laxity, scleral show, or hormone therapy use may be at greater risk for developing dry eyes or chemosis following surgery.

JAMA Facial Plast Surg. 2013 Jan 1;15(1):39-46. doi: 10.1001/2013.jamafacial.1.
Prischmann J, Sufyan A, Ting JY, Ruffin C, Perkins SW.