Thursday, January 28, 2010

Abstract: Boston keratoprosthesis (artificial cornea)

Don't get too excited - this is NOT for your run-of-the-mill miserable dry eye patient. It's for your ulcerated scarred visually impaired really exotic complicated case. Nonetheless, as a technological development it's very interesting so I wanted to mention it here.

The Boston Keratoprosthesis in 2 Patients With Autoimmune Polyendocrinopathy-Candidiasis-Ectodermal Dystrophy.
Cornea. 2010 Jan 21. [Epub ahead of print]
Yildiz EH, Saad CG, Eagle R, Ayres BD, Cohen EJ.

From the Wills Eye Institute, Jefferson Medical College, Thomas Jefferson University, Philadelphia, PA.
PURPOSE:: To report the results of Boston keratoprosthesis in patients with autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED).

CASE REPORTS:: Case 1 is a 36-year-old woman with APECED and ocular history of corneal ulcers in both eyes who presented with severe dry eyes. Her ocular examination showed diffuse corneal vascularization and stromal scarring in the left eye. She underwent Boston type 1 keratoprosthesis, cataract extraction, and sulcus intraocular lens implant in the left eye to improve visual acuity. Case 2 is a 49-year-old man with possible APECED and ocular history of phlyctenular keratitis, recurrent corneal erosions, and scarring presented with dense corneal vascularization and scarring in both eyes. He underwent a Boston type 1 keratoprosthesis, clear lens extraction, and posterior chamber intraocular lens implant in the right eye.

RESULTS:: The surgeries were uneventful. On postoperative day 1, visual acuity of 20/40 was achieved in both patients and it remained stable during the 2-year follow-up period. There were no postoperative complications seen in either patient.

CONCLUSIONS:: APECED is a rare disorder, which can be associated with bilateral keratitis or diffuse corneal vascularization in addition to systemic findings and ectodermal signs. The Boston type 1 keratoprosthesis is a promising treatment option to improve visual acuity in patients with APECED with corneal involvement.

Abstract: Liposomal spray

I think this is the product sold in the UK as Eye Logic (formerly Clarymist) and in the US as Tears Again Liposomal Spray.

Effect of a liposomal spray on the pre-ocular tear film.
Cont Lens Anterior Eye. 2010 Jan 20. [Epub ahead of print]
Craig JP, Purslow C, Murphy PJ, Wolffsohn JS.
Department of Ophthalmology, University of Auckland, New Zealand; Ophthalmic Research Group, Aston University, Birmingham, UK.

PURPOSE: With the potential to address evaporative dry eye, a novel spray has been developed in which phospholipid liposomes are delivered to the tear film via the surface of the closed eyelid. This study evaluated the short-term effects of liposomal spray application on the lipid and stability characteristics of the pre-ocular tear film in normal eyes.

METHODS: Twenty-two subjects (12M, 10F) aged 35.1+/-7.1 years participated in this prospective, randomised, double-masked investigation in which the liposomal spray was applied to one eye, and an equal volume of saline spray (control) applied to the contralateral eye. Lipid layer grade (LLG), non-invasive tear film stability (NIBUT) and tear meniscus height (TMH) were evaluated at baseline, and at 30, 60, 90 and 135min post-application. Subjective reports of comfort were also compared.

RESULTS: Treated and control eyes were not significantly different at baseline (p>0.05). Post-application, LLG increased significantly, at 30 and 60min, only in the treated eyes (p=0.005). NIBUT also increased significantly in the treated eyes only (p<0.001), at 30, 60 and 90min. TMH did not alter significantly (p>0.05). Comfort improved relative to baseline in 46% of treated and 18% of control eyes, at 30min post-application. Of those expressing a preference in comfort between the eyes, 68% preferred the liposomal spray.

CONCLUSIONS: Consistent with subjective reports of improved comfort, statistically and clinically significant improvements in lipid layer thickness and tear film stability are observed in normal eyes for >/=1h after a single application of a phospholipid liposomal spray. Crown Copyright © 2010. Published by Elsevier Ltd. All rights reserved.

Diagnosis & treatments: Conjunctivochalasis, excision and AMT

OSN SuperSite reported from Hawaiian Eye 2010 Dr. Hovanesian's suggestion for identifying conjunctivochalasis as a possible contributor to dry eye pain, with excision and AMT as the proposed treatment. (See article below.)

I have a request for the doctors performing these surgeries on conjunctivochalasis patients whose primary complaints are dry eye symptoms: Contact some of your patients who are 6-12 months or more out from surgery, and have them post on DryEyeTalk (and answer other patients' questions) or have them give me a call. I have heard from a lot of patients who returned to presurgical symptoms within that time period. I have not heard from a lot of success stories. In fact, I can remember at this moment a grand total of one. I shall remain skeptical until I start hearing from all these reportedly happy patients.

The difficulty with the classic patient of the type I hear from all the time, who has severe pain but limited ocular surface signs, is that they may have two or three things going on - some mild lagophthalmos, MGD, maybe conjunctivochalasis - but what is really causing their pain and how do you know? One of those? All of them? None of them - but rather nerve pain ala Perry Rosenthal's theories? It's impossible to tell without treating each problem, and this particular problem requires expensive and invasive treatment. However, I do appreciate that attention needs to be drawn to this as one of the factors that may be causing symptoms.

Test helps identify conjunctivochalasis in stubborn dry eye cases

KOLOA, Hawaii — A simple thumb test may help diagnose conjunctivochalasis in recalcitrant dry eye cases and result in a satisfied patient after surgical treatment, a speaker said here.

"Conjunctival chalasis is very easy to confuse with dry eye, and a simple thumb pressure test helps identify it," John A. Hovanesian, MD, said at Hawaiian Eye 2010.

While applying pressure to the lower outer eyelid with your thumb, have the patient move their eye up and down to identify the area of chemosis, Dr. Hovanesian said.

In a review of cases at his clinic, Dr. Hovanesian found eight patients who had a diagnosis of refractory dry eye who tested positive for conjunctivochalasis. He found that all patients were older than 50 years and had undergone previous ocular surgery. After a positive identification, all patients underwent an excision and amniotic membrane transplant with a fibrin tissue adhesive, and all patients had a complete resolution of symptoms.

"My take-home message today is to consider conjunctivochalasis in recalcitrant cases of 'dry eye,'" he said.

Abstract: Restasis after (oops) surgery

Correction: I originally noted this as a Restasis-after-cataract surgery study - very careless of me. Sorry about that. Thank you Dr. Fleming for pointing this out. So the comments below aren't really relevant to the study below.

Effects of postoperative cyclosporine ophthalmic emulsion 0.05% (Restasis) following glaucoma surgery.
Clin Experiment Ophthalmol. 2009 Dec;37(9):842-8.
Fakhraie G, Lopes JF, Spaeth GL, Almodin J, Ichhpujani P, Moster MR.

Wills Eye Institute, Philadelphia, Pennsylvania, USA.
Purpose: To determine if postoperative topical cyclosporine 0.05% has any beneficial effect following trabeculectomy

Methods: This was an interventional, randomized, prospective, double-masked clinical trial of 44 consecutive patients with uncontrolled glaucoma requiring filtration surgery. Ocular surface disease index questionnaire and comprehensive ocular exam, including Schirmer's tear test 1, were performed. Patients underwent routine trabeculectomy, with or without phacoemulsification. The study group (n = 22) received cyclosporine 0.05%, and the control group (n = 22) received artificial tears. Patients were evaluated at 1 and 6 months post surgery. Outcome measures were intraocular pressure, success rate, bleb appearance, ocular surface disease index, Schirmer's tear test 1 and conjunctival inflammation.

Results: Thirty-nine patients completed the study (19 in the study group, 20 in the control group). The mean baseline intraocular pressure was 23.8 +/- 12.6 mmHg in the study group and 25.9 +/- 10.6 mmHg in the control group (P = 0.513). Mean intraocular pressure at postoperative month 6 was 14.88 +/- 6.2 and 14.62 +/- 5.46 mmHg in the study group and control group, respectively (P = 0.837). There was no statistically significant difference in the mean values of Schirmer's tear test 1 and the level of conjunctival hyperaemia between the two groups at baseline, months 1 and 6 post surgery. The treatment group had a statistically significant decrease in ocular surface disease index score at 6 months (P = 0.003), indicating less severity of dry eye symptoms and significant reduction in ocular pain.

Conclusions: Topical cyclosporine 0.05% had no effect on postoperative bleb function and intraocular pressure following trabeculectomy, but improved subjective ocular surface symptoms in these patients.

Abstract: Validating part of another questionnaire (DEQ)

Validation of the 5-Item Dry Eye Questionnaire (DEQ-5): Discrimination across self-assessed severity and aqueous tear deficient dry eye diagnoses.
Cont Lens Anterior Eye. 2010 Jan 19. [Epub ahead of print]
Chalmers RL, Begley CG, Caffery B.

School of Optometry, Indiana University, Bloomington, IN, USA.
PURPOSE: To validate a subset of Dry Eye Questionnaire (DEQ) items that discriminate across self-assessed severity and various diagnoses of dry eye (DE).

METHODS: Subjects (n=260) in 2 studies received a clinical DE diagnosis, completed the 6-page DEQ and self-assessment of DE severity (SA-Sev). SA-Sev ratings were: 46 Severe, 107 Moderate, 77 Mild, and 46 None. Dry eye diagnoses were: 48 asymptomatic controls (C), 155 non-SS KCS, and 57 Sjögren Syndrome (SS). All DEQ items were correlated to SA-Sev by Spearman. Groups of highly correlated DEQ items were tested to discriminate SA-Sev; and the subset tested to distinguish across DE diagnosis.

RESULTS: The DEQ-5 comprises: frequency of watery eyes (r=0.48), discomfort (r=0.41), and dryness (r=0.35), and late day (PM) intensity of discomfort and dryness (r=0.42, 0.36) all significantly correlated to SA-Sev (p<0.01). Mean DEQ-5 scores by SA-Sev: Severe 14.9+/-2.3, Moderate 11.4+/-3.3, Mild 8.6+/-3.1 and None 2.7+/-3.2 (ANOVA, p<0.0001) and by DE diagnosis: C 2.7+/-2.9, non-SS KCS10.5+/-4.5 and SS14.0+/-3.4, differing significantly overall (Z=-8.6, p=0.000) and between diagnoses (X(2)=116.3, p=0.000). Watery eyes were reported primarily by non-SS KCS. Proposed screening criteria for the DEQ-5 are >6 for DE and >12 for suspected SS.

CONCLUSIONS: The DEQ-5, the sum of scores for frequency and PM intensity of dryness and discomfort plus frequency of watery eyes, effectively discriminated across self-assessed severity ratings and between patients with DE diagnoses. These results indicate that DEQ-5 scores >6 suggest DE and scores >12 may indicate further testing to rule out SS-DE

Drug news: Alcon picks up Zyclorin from Sirion

Alcon finally puts some substance into its dry eye portfolio by grabbing Sirion's Zyclorin (cyclosporine A 0.1%). Gotta double the Allergan ante I guess.

Zyclorin is a bit of a dark horse (at least to those of us who don't consult for pharmaceuticals) - one of those you hear no buzz about until they're almost done. It's 0.1% cyclosporine A and according to the NIH clinicals site, a Phase III study was completed almost two years ago. The Sirion site simply indicates it's in Phase III and Alcon is tight-lipped about the status.

Alcon to Purchase Ophthalmic Pharmaceutical Assets from Sirion

HUENENBERG, Switzerland, Jan 18, 2010 (BUSINESS WIRE) -- Alcon (NYSE: ACL), the world's leader in eye care, announced today that it will purchase the rights in the United States for two FDA-approved topical eye care products from Sirion Therapeutics, Inc. The two products purchased are Durezol(TM), a marketed ophthalmic corticosteroid approved for the treatment of inflammation and pain associated with eye surgery, and Zirgan(TM), a recently approved antiviral for the treatment of acute herpetic keratitis (corneal ulcers). In addition to these marketed products, Alcon also acquired the global rights, excluding Latin America, for Zyclorin(TM). This product is currently in clinical development to treat dry eye and other ocular surface diseases.

Drug news: Prolacria is done, for the last time.

After a valiant, not to say obdurate, struggle, Prolacria has once again disappointed, this time failing to deliver needed results in its latest Phase III trial, in the face of recent relatively buoyant investor expectations.

While I haven't seen an actual epitaph, I think it can be taken for granted that no more money will be invested in this drug. It's been a long haul and you all tried your best... what a shame it didn't work out. You've got a lot of fans out there.

Inspire Announces Results Of Phase 3 PROLACRIA™ Trial For Dry Eye

Inspire Pharmaceuticals, Inc. (NASDAQ: ISPH) announced that its Phase 3 clinical trial (Trial 03-113) of PROLACRIA™ (diquafosol tetrasodium ophthalmic solution) 2% for the treatment of dry eye disease did not meet its primary endpoint (p = 0.526) or its secondary endpoint (p = 0.368).

"We have provided the top-line results from this trial to our partner Allergan and we will be conducting a thorough review of the program before determining next steps, if any," stated Christy L. Shaffer, Ph.D., President and CEO of Inspire.

Trial 03-113 was a six-week, randomized, placebo-controlled trial in 490 patients who had a fluorescein staining score of three in the central region of the cornea at baseline, using the National Eye Institute scale of zero to three. The primary endpoint was the proportion of subjects receiving PROLACRIA, administered four times daily as eye drops, that achieved clearing, or a staining score of zero, in the central region of the cornea in the study eye at the six-week trial endpoint, compared to those receiving placebo. The secondary endpoint was the proportion of patients receiving PROLACRIA that achieved greater than or equal to a two-unit reduction in staining scores at the six-week trial endpoint, compared to those receiving placebo.

Abstract: Demodex mites facial rosacea and bleph

Yes, I know exactly how many of you are pricking up your ears at this one!

Correlation between Ocular Demodex Infestation and Serum Immunoreactivity to Bacillus Proteins in Patients with Facial Rosacea.
Ophthalmology. 2010 Jan 14. [Epub ahead of print]
Li J, O'Reilly N, Sheha H, Katz R, Raju VK, Kavanagh K, Tseng SC.

Ocular Surface Center, Miami, Florida; Ocular Surface Research Education Foundation, Miami, Florida; The First Affiliated Hospital of Guangzhou Medical College, Guangzhou, China.

PURPOSE: To investigate correlation between ocular Demodex infestation and serum.

DESIGN: A prospective study to correlate clinical findings with laboratory data.

PARTICIPANTS: We consecutively enrolled 59 patients: 34 men and 25 women with a mean age of 60.4+/-17.6 years (range, 17-93). METHODS: Demodex counting was performed based on lash sampling. Serum immunoreactivity to two 62-kDa and 83-kDa proteins derived from B oleronius was determined by Western blot analysis. Facial rosacea, lid margin, and ocular surface inflammation were documented by photography and graded in a masked fashion.

MAIN OUTCOME MEASURES: Statistical significance based on correlative analyses of clinical and laboratory data.

RESULTS: These 59 patients were age matched, but not gender matched, regarding serum immunoreactivity, ocular Demodex infestation, or facial rosacea. There was a significant correlation between serum immunoreactivity and facial rosacea (P = 0.009), lid margin inflammation (P = 0.040), and ocular Demodex infestation (P = 0.048), but not inferior bulbar conjunctival inflammation (P = 0.573). The Demodex count was significantly higher in patients with positive facial rosacea (6.6+/-9.0 vs. 1.9+/-2.2; P = 0.014). There was a significant correlation of facial rosacea with lid margin inflammation (P = 0.016), but not with inferior bulbar conjunctival inflammation (P = 0.728). Ocular Demodex infestation was less prevalent in patients with aqueous tear-deficiency dry eye than those without (7/38 vs. 12/21; P = 0.002).

CONCLUSIONS: The strong correlation provides a better understanding of comorbidity between Demodex mites and their symbiotic B oleronius in facial rosacea and blepharitis. Treatments directed to both warrant future investigation.

Abstract: Variations on the Azasite theme

Don't get too excited yet - it's only at the bunny stage.

Ocular surface distribution and pharmacokinetics of a novel ophthalmic 1% azithromycin formulation.
J Ocul Pharmacol Ther. 2009 Oct;25(5):433-9.
Akpek EK, Vittitow J, Verhoeven RS, Brubaker K, Amar T, Powell KD, Boyer JL, Crean C.
The Ocular Surface Diseases and Dry Eye Clinic, The Wilmer Eye Institute, Johns Hopkins Hospital, Baltimore, Maryland, USA.

PURPOSE: To investigate the ocular distribution of 1% azithromycin ophthalmic solution and the effect of polycarbophil-based mucoadhesive formulation on ocular tissue levels of azithromycin after single and multiple topical administrations in the rabbit eye.

METHODS: Rabbits were treated with either a single administration of 1% azithromycin solution with or without polycarbophil, or with multiple administrations of 1% azithromycin solution in polycarbophil. Drug concentrations were measured using LC/MS/MS. Conjunctiva, cornea, aqueous humor, and tear samples were analyzed over a period of 144 h after a single administration of azithromycin with or without polycarbophil. Eyelid, conjunctiva, cornea, aqueous humor, and tear samples were collected over a period of 288 h during and after multiple administrations of azithromycin.

RESULTS: Azithromycin was rapidly absorbed and distributed in the ocular tissues, reaching within 5 min, concentrations of 10,539 microg/mL in tear film, 108 microg/g in conjunctiva, and 40 microg/g in the cornea. The drug demonstrated tissue-specific half-lives of 15, 63, and 67 h, respectively. Following multiple administrations, the drug gradually accumulated. The polycarbophil formulation increased the bioavailability of the drug, producing peak concentrations that were between 5- and 12-fold higher than those without polycarbophil. Azithromycin also distributed rapidly in the eyelids, reaching peak concentrations of 180 mug/g at the end of the 7-day treatment, and was eliminated with a half-life of 125 h. Six days after treatment was discontinued, eyelid levels of azithromycin were above 40 microg/g.

CONCLUSIONS: Sustained and high concentrations were encountered with 7-day approved administration of 1% azithromycin formulation (AzaSite, Inspire Pharmaceuticals, Inc., Durham, NC) within all ocular surface tissues, particularly the lids. Many ocular surface disorders involving the tear film, eyelids, and adnexal structures are associated with chronic, low-grade bacterial infection and may potentially lead to decreased vision secondary to corneal scarring. Various topical antibiotic and steroid combinations with or without oral tetracyclines are commonly used with variable clinical response and known potential side effects. The clinical relevance of this study is unknown; however, the long-lasting antibacterial and additional anti-inflammatory properties of topical azithromycin might offer an effective alternative treatment option and should be explored further in clinical studies.

Abstract: More about OSDI

Some day, a good genie from the far land of Xerophthalmia will appear and grant me one wish: free access to all the medical journals I want. Or a debit card to purchase the ones that pique my interest. Till then, I will simply keep reading these with my tongue hanging out for more information.

Minimal clinically important difference for the ocular surface disease index.
Miller KL, Walt JG, Mink DR, Satram-Hoang S, Wilson SE, Perry HD, Asbell PA, Pflugfelder SC.
Arch Ophthalmol. 2010 Jan;128(1):94-101
ICON Clinical Research, 188 Embarcadero, Ste 200, San Francisco, CA 94105, USA.

OBJECTIVE: To assess the minimal clinically important difference (MCID) for the Ocular Surface Disease Index (OSDI; Allergan Inc, Irvine, California, holds the copyright), a 12-item patient-reported outcome questionnaire designed to quantify ocular disability due to dry eye disease.

METHODS: Study data were collected within the Restasis Review of Efficacy and Safety vs Tears in the Relief of Dry Eye (RESTORE), an observational registry. A clinician global impression (CGI) and a subject global assessment (SGA) served as anchors to estimate the MCID for the overall OSDI score (range, 0-100). The overall OSDI score defined the ocular surface as normal (0-12 points) or as having mild (13-22 points), moderate (23-32 points), or severe (33-100 points) disease. RESTORE patients were included if they completed the OSDI at the baseline visit and at a follow-up visit and had a global change rating (SGA or CGI).

RESULTS: Three hundred ten patients were included (82.3% white and 81.6% female [mean age, 57.8 years]). The CGI and SGA correlated with the OSDI score change for all OSDI categories except the normal category. The MCID ranged from 7.0 to 9.9 for all OSDI categories. The MCID ranged from 4.5 to 7.3 for mild or moderate disease and from 7.3 to 13.4 for severe disease.

CONCLUSIONS: Using observational data, we estimated the MCIDs for different baseline OSDI categories of dry eye disease. These results will assist clinicians and researchers when interpreting OSDI score changes.

Abstract: Improvement to interferometry tear film measurements

Robust estimation of tear film surface quality in lateral shearing interferometry.
Szczesna DH, Iskander DR.
J Biomed Opt. 2009 Nov-Dec;14(6):064039.
Wroclaw University of Technology, Institute of Physics, Wybrzeze Wyspianskiego 27, Wroclaw, 50-370, Poland.

Interferometry is a sensitive technique for recording tear film surface irregularities in a noninvasive manner. At the same time, the technique is hindered by natural eye movements resulting in measurement noise. Estimating tear film surface quality from interferograms can be reduced to a spatial-average-localized weighted estimate of the first harmonic of the interference fringes. However, previously reported estimation techniques proved to perform poorly in cases where the pattern fringes were significantly disturbed. This can occur in cases of measuring tear film surface quality on a contact lens on the eye or in a dry eye. We present a new estimation technique for extracting the first harmonic from the interference fringes that combines the traditional spectral estimation techniques with morphological image processing techniques. The proposed technique proves to be more robust to changes in interference fringes caused by natural eye movements and the degree of dryness of the contact lens and corneal surfaces than its predecessors, resulting in tear film surface quality estimates that are less noisy.

Image verification on comments

I've recently been getting pummeled with spam via the 'comments' feature here, so I have had to turn on the 'image verification' feature. Apologies in advance as I know those are a nuisance.