Sunday, January 16, 2011

Abstract: Thermal punctal cautery

The patients in this study who underwent thermal cautery all had a history of plugs falling out. Just as a matter of interest I wonder whether a single type of plug was used or other types were tried when the first ones came out. I'm not against cautery by any means (used appropriately...) but I think that it can be a service to the patient to experiment with different plug types.

Surgical Punctal Occlusion with a High Heat-Energy-Releasing Cautery Device for Severe Dry Eye with Recurrent Punctal Plug Extrusion.

To report the rate of recanalization and the efficacy of punctal occlusion surgery with a high heat-energy-releasing cautery device in patients with severe dry eye disease and recurrent punctal plug extrusion.

Prospective, interventional case series.

Seventy puncta from 44 eyes of 28 dry eye patients underwent punctal occlusion with thermal cautery. All patients had a history of recurrent punctal plug extrusion. A high heat-energy-releasing thermal cautery device (Optemp II V; Alcon Japan) was used for punctal occlusion surgery. Symptom scores, best-corrected visual acuity, fluorescein staining score, rose bengal staining score, tear film break-up time, and Schirmer test values were compared before and 3 months after the surgery. Rate of punctal recanalization also was examined.

Three months after surgical cauterization, symptom score decreased from 3.9 ± 0.23 to 0.56 ± 0.84 (P < .0001). Logarithm of the minimal angle of resolution best-corrected visual acuity improved from 0.11 ± 0.30 to 0.013 ± 0.22 (P = .003). Fluorescein staining score, rose bengal staining score, tear film break-up time, and the Schirmer test value also improved significantly after the surgery. Only 1 of 70 puncta recanalized after thermal cauterization (1.4%).

Punctal occlusion with the high heat-energy-releasing cautery device not only was associated with a low recanalization rate, but also with improvements in ocular surface wetness and better visual acuity.

Am J Ophthalmol. 2011 Jan 11. [Epub ahead of print]
Ohba E, Dogru M, Hosaka E, Yamazaki A, Asaga R, Tatematsu Y, Ogawa Y, Tsubota K, Goto E.
Department of Ophthalmology, School of Dental Medicine, Tsurumi University, Yokohama, Japan.

Abstract: Botox for hemifacial spasm or blepharospasm improving dry eye symptoms

This is all well and good but any study with the words Botox and Dry Eye must also talk about risks. There is risk of freezing the eye open which is going to make dry eye massively worse for three months. Anyone pursuing this treatment needs a very experienced doctor who knows how much and where to shoot to maximize safety.

Botulinum toxin type A influence on the lacrimal function of patients with facial dystonia.
[Article in Portuguese]

To analyze the influence of botulinum toxin on the lacrimal function of patients with facial dystonias.

Patients with the diagnosis of hemifacial spasm or benign essential blepharospasm were evaluated and invited to answer the Ocular Surface Index Disease (OSID) questionnaire. All patients underwent Schirmer I and basal tests; break-up time (BUT) test and lacrimal clearance evaluation. On the following day, the patients were treated with botulinum toxin. The Ocular Surface Index Disease questionnaire and all the initial tests were reapplied 30 days after the treatment by the same examiner.

Twenty-six patients were enrolled in this study, 15 (57.7%) with hemifacial spasm and 11 (42.3%) with benign essential blepharospasm. The mean age of patients with hemifacial spasm was 70.9 ± 13.3 years and the male:female ratio was 1:1.5. In the group of patients with benign essential blepharospasm, the mean age was 68.9 ± 8.4 years with a female preponderance (90.0%). After the treatment, the Ocular Surface Index Disease score, Schirmer I and basal tests score decreased in both groups. The mean of Break-up time test increased significantly in both groups. The lacrimal clearance evaluation showed a greater number of eyes that achieved a complete drainage of the tears after the treatment in both groups.

The treatment with botulinum toxin improved dry eye symptoms in patients with facial dystonia. Despite of the aqueous portion of tear have decreased, blink modifications improved the tear stability and drainage.

Arq Bras Oftalmol. 2010 Oct;73(5):405-408.
Oliveira FC, Oliveira GC, Cariello AJ, Felberg S, Osaki MH.
Departamento de Oftalmologia, Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, SP, Brasil.

Abstract: Dry eye pharmacotherapy - literature review summing it up

Pharmacotherapy of dry eye.

Based on data from the largest studies of dry eye to date - the Women's Health Study (WHS) and the Physicians' Health Study (PHS) - and other studies, it has been estimated that about 3.23 million women and 1.68 million men, for a total of 4.91 million Americans aged ≥ 50 years, have dry eye. Tens of millions more have less severe symptoms and probably a more episodic manifestation of the disease that is notable only during contact with some adverse contributing factor(s), such as low humidity or contact lens wear. Dry eye disease is a common yet frequently under-recognized public health problem whose etiology and management challenge clinicians and researchers involved in this field.

Areas covered:
Advances in the understanding of the disease have been made over the past 10 years in areas of epidemiology, pathogenesis, clinical manifestation, and possible therapy. Historical aspects and recent information in relation to the use of artificial tear substitutes and anti-inflammatory agents in dry eye disease, including topical cyclosporin and corticosteroids, autologous serum, tetracyclines and systemic immunosuppressants, are covered in this review. The reader will gain insight into the recent views on the pharmacological menu of treatments for dry eyes following the recommendations of the 2007 International Dry Eye Workshop.

Expert opinion:
Dry eye is a visually disabling disease, the treatment of which needs tailoring according to the type and severity of dry eye disease.

Expert Opin Pharmacother. 2011 Jan 10. [Epub ahead of print]
Dogru M, Tsubota K.
Keio University School of Medicine, Johnson & Johnson Ocular Surface and Visual Optics Department, Tokyo, Japan.

Abstract: Another way to deliver cyclosporine

Ocular biocompatibility of novel Cyclosporin A formulations based on methoxy poly(ethylene glycol)-hexylsubstituted poly(lactide) micelle carriers.

Topical ocular drug delivery has always been a challenge for pharmaceutical technology scientists. In the last two decades, many nano-systems have been studied to find ways to overcome the typical problems of topical ocular therapy, such as difficult corneal penetration and poor drug availability. In this study, methoxy poly(ethylene glycol)-hexylsubstituted poly(lactides) (MPEG-hexPLA) micelle formulations, which are promising nanocarriers for poorly water soluble drugs, were investigated for the delivery of Cyclosporin A (CsA) to the eye. As a new possible pharmaceutical excipient, the ocular compatibility of MPEG-hexPLA micelle formulations was evaluated. An in vitro biocompatibility assessment on human corneal epithelial cells was carried out using different tests. Cytotoxicity was studied by using the [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide] (MTT), and clonogenic tests and revealed that the CsA formulations and copolymer solutions were not toxic. After incubation with MPEG-hexPLA micelle formulations, the activation of caspase-dependent and -independent apoptosis as well as autophagy was evaluated using immunohistochemistry by analyzing the localization of four antibodies: 1) anti-caspase 3; 2) anti-apoptotic inducing factor (AIF); 3) anti IL-Dnase II and 4) anti-microtubule-associated protein 1 light chain 3 (LC3). No apoptosis was induced when the cells were treated with the micelle solutions that were either unloaded or loaded with CsA. The ocular tolerance was assessed in vivo on rabbit eyes by Confocal Laser Scanning Ophthalmoscopy (CLSO), and very good tolerability was seen. The observed corneal surface was comparable to a control surface that was treated with a 0.9% NaCl solution. In conclusion, these results demonstrate that MPEG-hexPLA micelles are promising drug carriers for ocular diseases involving the activation of cytokines, such as dry eye syndrome and autoimmune uveitis, or for the prevention of corneal graft rejection.

Int J Pharm. 2011 Jan 7. [Epub ahead of print]
Di Tommaso C, Torriglia A, Furrer P, Behar-Cohen F, Gurny R, Möller M.
School of Pharmaceutical Sciences, Pharmaceutics, University of Geneva, University of Lausanne, 30 Quai Ernest Ansermet, CH-1211 Geneva 4, Switzerland.

Drug news: Celtic Therapeutics acquires RX-10045 from Resolvyx

...and Phase III clinical is still supposed to start this half of 2011.

Celtic licenses Resolvyx Pharma dry eye syndrome compound

Celtic Therapeutics has licensed and taken over worldwide rights related to Resolvyx Pharmaceuticals' RX-10045 as a treatment of dry eye syndrome and other ophthalmic conditions.

Resolvyx Pharma has scheduled RX-10045 Phase III randomized, placebo-controlled, multi-center study in 2011.

Under the agreement, Celtic Therapeutics may also license rights to and develop a second Resolvyx compound in a topical formulation for ophthalmic indications.

Abstract: Testing fluorescein punctate staining

Fluorescein Punctate Staining Traced to Superficial Corneal Epithelial Cells by Impression Cytology and Confocal Microscopy.

The basis of fluorescein associated superficial punctate staining in dry eyes is controversial. Prior explanations include fluorescein pooling in surface erosive defects, intercellular trapping of fluorescein, and intracellular staining in dead cells. The hypothesis that punctate "erosions" are individual cells with enhanced fluorescence is tested.

Ten impression cytology membrane materials were compared to optimize cellular yield in buccal mucosa and cornea. Clinical-cytologic correlation of punctate fluorescent spots was performed in four dry eye patients. Individual punctate spots were localized by fiducials in photographs before and after removal with impression membranes and traced in fluorescence microscopy and cytologic stains. Punctate spots were correlated with cells removed by the membrane using two way contingency table analysis. Clinico-pathologic correlation of punctate spots was performed in ten corneas removed in dry eye patients receiving transplants for concurrent diseases. Punctate fluorescence was tracked in specimens by fiducials, and epifluorescence. The distribution of fluorescent spots in specific cell layers of the cornea was determined by confocal microscopy.

Cellular yield was greatest with impressions from polytetrafluoroethylene (PTFE, Teflon, Biopore) membrane compared to its closest rival (p=0.019). Punctate fluorescent spots that disappeared after impression cytology (71%) correlated to cells on membranes (p=0.009). The punctate spots were more frequent in the superficial cell layers of the cornea (80%) compared to the deepest 2 layers (0%) (p<0.00049).

Punctate epithelial "erosions" correspond to enhanced fluorescence in epithelial cells predominantly in superficial layers of the cornea and would be more aptly named fluorescent epithelial cells (FLECs).

Invest Ophthalmol Vis Sci. 2011 Jan 6. [Epub ahead of print]
Mokhtarzadeh M, Casey R, Glasgow BJ.
Jules Stein Eye Institute.

Abstract: A model for wetting and evaporation of a post-blink precorneal tear film

And more from the same journal...

A model for wetting and evaporation of a post-blink precorneal tear film.

We examine a fluid dynamic model for the evolution of a precorneal tear film that includes evaporation of the aqueous layer and a wetting corneal surface. Our model extends previous work on the break-up time for a post-blink tear film to include a more realistic model for evaporation. The evaporation model includes the effects of conjoining pressure and predicts the existence of an equilibrium adsorbed fluid layer that serves as a model for a wetting corneal surface/mucin layer. The model allows the prediction of dewetting rates that are compared with experimental measurements. By choosing an expected thickness where evaporation and conjoining pressure balance, we obtain qualitative agreement for the opening rate with in vivo observations.

Math Med Biol. 2010 Sep;27(3):211-25. Epub 2009 Oct 27.
Winter KN, Anderson DM, Braun RJ.
Department of Mathematical Sciences, George Mason University, Fairfax, VA 22030, USA. [email][/email]

Abstract: Tear film dynamics on a eye-like thing... pressure boundary conditions

I'm too ignorant to comment on this sort of thing except to say that I really love to see anything where they're looking at the ocular surface with an eye to physics not just chemistry. Naturally, this was not published in an ophthalmology journal.

Before the Dark Ages of dry eye in the nineties and the Age of Restasis in the noughties, some of the best dry eye science... like Dr. Holly's in the eighties... was more inclined to work in that direction.

Tear film dynamics on an eye-shaped domain I: pressure boundary conditions.

We study the relaxation of a model for the human tear film after a blink on a stationary eye-shaped domain corresponding to a fully open eye using lubrication theory and explore the effects of viscosity, surface tension, gravity and boundary conditions that specify the pressure. The governing non-linear partial differential equation is solved on an overset grid by a method of lines using a finite-difference discretization in space and an adaptive second-order backward-difference formula solver in time. Our 2D simulations are calculated in the Overture computational framework. The computed flows show sensitivity to both our choices between two different pressure boundary conditions and the presence of gravity; this is particularly true around the boundary. The simulations recover features seen in 1D simulations and capture some experimental observations including hydraulic connectivity around the lid margins.

Math Med Biol. 2010 Sep;27(3):227-54. Epub 2010 Jan 11.
Maki KL, Braun RJ, Henshaw WD, King-Smith PE.
Department of Mathematical Sciences, University of Delaware, Newark, DE 19711, USA.

Abstract: As you probably know, computers are harder on your eyes than books

A comparison of symptoms after viewing text on a computer screen and hardcopy.

Computer vision syndrome (CVS) is a complex of eye and vision problems experienced during or related to computer use. Ocular symptoms may include asthenopia, accommodative and vergence difficulties and dry eye. CVS occurs in up to 90% of computer workers, and given the almost universal use of these devices, it is important to identify whether these symptoms are specific to computer operation, or are simply a manifestation of performing a sustained near-vision task.

This study compared ocular symptoms immediately following a sustained near task. 30 young, visually-normal subjects read text aloud either from a desktop computer screen or a printed hardcopy page at a viewing distance of 50 cm for a continuous 20 min period. Identical text was used in the two sessions, which was matched for size and contrast. Target viewing angle and luminance were similar for the two conditions. Immediately following completion of the reading task, subjects completed a written questionnaire asking about their level of ocular discomfort during the task.

When comparing the computer and hardcopy conditions, significant differences in median symptom scores were reported with regard to blurred vision during the task (t = 147.0; p = 0.03) and the mean symptom score (t = 102.5; p = 0.04). In both cases, symptoms were higher during computer use.

Symptoms following sustained computer use were significantly worse than those reported after hard copy fixation under similar viewing conditions. A better understanding of the physiology underlying CVS is critical to allow more accurate diagnosis and treatment. This will allow practitioners to optimize visual comfort and efficiency during computer operation.

Ophthalmic Physiol Opt. 2011 Jan;31(1):29-32.
Chu C, Rosenfield M, Portello JK, Benzoni JA, Collier JD.
SUNY College of Optometry, State University of New York, New York, USA.

Drug news: InSite Vision submits ISV-101

InSite Vision submits ISV-101 investigational NDA with FDA

InSite Vision has submitted ISV-101 investigational new drug (IND) application with the US Food and Drug Administration (FDA) as a treatment for treat dry eye disease.

The company expects to initiate a Phase 1/2 clinical trial to investigate the safety and efficacy of the drug, in 2011.

ISV-101 combines a low dose of the non-steroidal anti-inflammatory (NSAID) bromfenac (Bromday/Xibrom marketed by ISTA Pharmaceuticals) with InSite Vision's proprietary DuraSite technology.

InSite Vision said that the initial data from clinical studies evaluating the combination of DuraSite with a higher dose of bromfenac have demonstrated a favorable safety profile.

InSite Vision CEO Timothy Ruane said that with patent protection extending into 2029, they believe ISV-101 can be well positioned to compete in the expanding $500m US dry eye market.

Abstract: Topical tetracycline in rabbit dry eye model

This is from a veterinary journal but I thought I'd include it here for those that have been following the use of topical doxycycline in dry eye/MGD.

Efficacy of topically applied liposome-bound tetracycline in the treatment of dry eye model.

To evaluate the effects of liposome-bound tetracycline eye drops in a rabbit dry eye model evaluating their advantage of being less allergic, preservative free and prolonged action compared with other tear substitutes.

New Zealand albino rabbits were equally divided into control group and dry eye induced groups. Dryness was induced in 24 eyes of 12 healthy adult male albino rabbits by instilling atropine sulfate eye drops 1% three times daily for 1 week, then animals were subdivided into four groups; group 1 (rabbits with dry eye model), groups 2, 3, and 4: rabbits with dry eye model treated for 7 days starting on 7th day of dryness induction with either tetracycline, empty liposome, or combined tetracycline with liposome as topical eye drops respectively. Schirmer (STT) test and tear break up time (TBUT) were assessed on days 0, 2, 4, 7, 9, 11, and 14. Animals were sacrificed on day 14 and histopathological examination of the cornea and conjunctiva was performed.

Tear break up time and STT test values were significantly improved in groups 2, 3, 4 as compared with group 1. The histopathological examination showed normal cytoarchitecture of corneas and conjunctivae in groups 2, 3, 4 against the dryness effect that continued to affect the cornea and conjunctival epithelium in group 1. There was a significant improvement in the group treated with liposome-bound tetracycline eye drops (group 4) as compared with tetracycline alone (group 2) and empty liposome (group 3).

The use of liposome encapsulated tetracycline significantly improved STT and TBUT values as well as reverse surface ocular pathology.

Vet Ophthalmol. 2011 Jan;14(1):18-25. doi: 10.1111/j.1463-5224.2010.00834.x.
Shafaa MW, El Shazly LH, El Shazly AH, El Gohary AA, El Hossary GG.
Department of Physics, Faculty of Science, Helwan University, Cairo, Egypt Department of Ophthalmology and Pathology, Memorial Institute of Ophthalmology, Giza, Egypt Departments of Physiology and Pharmacology, Research Institute of Ophthalmology, Giza, Egypt.

Scratch that... I'm back

Should have looked before I leapt. I am not very blog savvy and didn't realize that people who aren't registered members of DryEyeTalk would not be able to 'follow' the blog from that location. So, till I can find a reasonable workaround I will just try to maintain the blog in both places.