Wednesday, July 30, 2008

Abstract: Tobacco smoke and eye disease

Who woulda thunk.

Considering how many people smoke, I found it absolutely astonishing to read in this abstract how few studies there are about environmental smoke and anything eye-related. And of the grand total of 7 studies, 0 are related to dry eye.

Environmental tobacco smoke (ETS) exposure and eye disease.Br J Ophthalmol. 2008 Jul 25. [Epub ahead of print]
Lois N, Abdelkader E, Reglitz K, Garden C, Ayres J.

PURPOSE: To undertake a systematic review of the literature on the effect of environmental tobacco smoke (ETS) and eye disease.

METHODS: Medline (1950-January Week 2 2007), EMBASE (1980 to 2007 Week 07), SCOPUS and Science Direct were searched on ETS exposure and eye disease using various combinations of the following terms: Passive smoking, environmental tobacco smoke, sidestream smoke, involuntary smoking, secondhand smoke; with eye, conjunctiva, sclera, episclera, cornea, lens, iris, retina, choroid, uvea, optic nerve, uveitis, iritis, blindness, visual loss, cataract, thyroid eye disease, conjunctivitis, age-related macular degeneration, dry eye, tears. The above terms were also used to search abstracts published on The Association for Research in Vision and Ophthalmology Annual Meeting abstracts, from 1995 to 2006, and the grey literature, including PhD and MSc theses/dissertations. A search was further conducted specifically on eye diseases where active smoking has been proposed to be a risk factor, including age-related macular degeneration, Graves' ophthalmology, glaucoma, uveitis, refractive errors, strabismus, tobacco-alcohol amblyopia, non-arteritic ischemic optic neuropathy, Leber's optic neuropathy and diabetic retinopathy. Given the scarce number of studies found through the above search, all articles found on ETS and eye disease were included in this review.

RESULTS: Seven studies evaluated the possible relationship between ETS and an eye disease. These studies referred to refractive errors in children (n=2), cataract (n=1), age-related macular degeneration (n=3) and Grave's ophthalmopathy (n=1). The data available was insufficient to establish conclusive relationships between ETS and these eye diseases.

CONCLUSION: Very scarce data exists in the literature on the effect of ETS on diseases of the eye. It seems appropriate that ETS should be included in future studies addressing the effect of smoking on eye disease.

Abstract: More T cell stuff

Ugh. I love IOVS but this stuff drives me bananas... I'm not in the mood to attempt translation.

In Vitro Expanded CD4+CD25+Foxp3+ Regulatory T Cells Maintain a Normal Phenotype and Suppress Immune-Mediated Ocular Surface Inflammation.
Invest Ophthalmol Vis Sci. 2008 Jul 24. [Epub ahead of print]
Siemasko KF, Gao J, Calder VL, Hanna R, Calonge M, Pflugfelder SC, Niederkorn JY, Stern ME

Purpose: To determine if in vitro expanded CD4+CD25+Foxp3+ regulatory T cells can suppress immune-mediated ocular surface inflammation in a mouse model of dry eye.

Methods: C57BL/6 or BALB/c mice were exposed to a dry, desiccating environment produced by maintaining low humidity (<40%), injections of scopolamine, and air flow produced by a fan. CD4+CD25+ regulatory T cells were isolated and expanded in vitro in the presence of rmIL-2 and beads coated with anti-CD28 and anti-CD3. In vitro expanded regulatory T cells were phenotypically compared to freshly isolated regulatory T cells by flow cytometry and immunofluorescence. T cell-deficient nude mice were reconstituted with CD4+ T-effector cells from donor mice exposed to a desiccating environment for 5 days in combination with or without freshly isolated or in vitro expanded regulatory T cells. Tear cytokine levels were determined by multiplex bead-based immunoassay (Luminex).

Results: In vitro regulatory T cells maintained normal levels of CD4+, CD25+, and intracellular Foxp3+ as determined by flow cytometry and immunohistochemistry. Freshly isolated and in vitro regulatory T cells were titrated in the presence of CD4+ pathogenic T cells (CD4+Path T cells) in reconstitution experiments and most efficiently ablated tear cytokine levels and conjunctival cellular infiltration at a ratio of 1:1 (T Regs: CD4+Path).

Conclusions: Regulatory T cells expressed CD4+, CD25+, and intracellular Foxp3+ at normal levels and retained their inhibitory function after in vitro expansion, providing a useful tool to determine the mechanism regulatory T cells use to sustain a homeostatic environment on the ocular surface.

Abstract: Systane after cataract surgery

Infomercial for Systane...

[Systane and cataract surgery]
Oftalmologia. 2007;51(4):100-4.[Article in Romanian]
Stefan C, Dumitrica DM

PURPOSE: To emphasize and measure the effect of post-cataract surgery Systane treatment. SETTING: Eye Clinic - Central Clinical Hospital - Bucharest, Romania.

METHODS: Six months clinical, observational, prospective, double-masked study on two groups of patients with cataract surgery (phacoemulsification technique) performed by the same surgeon. Group A (19 patients) received topic treatment with Systane and group B (17 patients) topic treatment with purified water (both with the same presentation form), associated with classical postoperatively treatment. Each patient answered a standardized questionnaire about subjective symptoms of ocular discomfort Several clinical tests were performed for both groups: Schirmer 1 test, tear break-up time (TBUT) and fluorescein staining showing epithelial defects. The groups were homogeneous about the age and sex distribution. Exclusion criteria: any ocular or general associated disease. Statistic analyse: t-student test.

RESULTS: First examination (after one week treatment) show that 73,68% patients treated with Systane did not have subjective symptoms comparing with 47,05% patients without Systane. Final tests (3 week examination) results for subjective symptoms were improved in both groups: 94,73% group A and 70,58% group B (p<0,001). Abnormal values (under 10 mm) for Schirmer 1 test were found in 17,64% of group B patients comparing with 11,76% patients of group A at the first examination. Final Schirmer 1 test results are statistically better in group A 100%-normal values, comparing with 88,23%-normal values in group B. The stability of tear film (TBUT) is altered in 52,94% of purified water treated patients; only in 21,05% of Systane patients existing this problem at the first examination (p<0,001). After 3 weeks treatment 23,52% group B patients and 5,26% group A patients had TBUT altered. Initially fluorescein staining is present in 4 group B patients and in 1 group A patient, comparing with only 1 group B patient in final tests.

CONCLUSIONS: Cataract surgery can affect ocular tear film production and stability by many factors including postoperatively anti-inflammatory classical treatment. Systane prevents the signs and symptoms of tear film insufficiency, decrease post surgery complications and improve epithelial repair. Systane gives a higher satisfaction to the patient associated with a healthy and stable ocular surface.

Abstract: Salivary gland transplantation

To be honest this stuff makes me shudder - especially the complications part. I'd much rather see people stick with environmental control in the form of moisture chambers, sclerals or both. But I know there are plenty of people out there interested in it so I'm passing it along... It's a pretty straightforward read.

Minor salivary gland transplantation.Dev Ophthalmol. 2008;41:243-54.
Geerling G, Raus P, Murube J.

INTRODUCTION: Minor oral salivary glands exist in large numbers in the labial, buccal and palatal mucosa, and account for approximately half of the baseline secretion of saliva. They can be transplanted together with the overlying mucosa as a complex graft to the posterior lamella of the eyelids to increase ocular surface lubrication and reduce discomfort in dry eyes.

MATERIAL AND METHODS: The surgical methods and the results of this technique in 17 patients are described. All patients had been retractive to medical treatment. The recipient bed over the lower or upper lid retractors and a donor tissue of lower labial mucosa with its submucosal minor salivary glands of approximately 2.5 x 2 cm were prepared by means of a surgical knife or Ellman Surgitron high-frequency/low-temperature radiosurgical device. The graft was cut in two strips of approximately 2.5 x 1 cm size and sutured to the recipient site with interrupted or running sutures. The labial wound was left open for second intention healing.

RESULTS: All grafts remained viable and vascularised within 1 week. Vascularisation of the graft was associated with an improvement of symptoms and increased ocular surface lubrication. Complications included temporary labial hypaesthesia, partial necrosis of the graft (n = 1), herpes simplex virus keratitis (n = 1) and epiphora (n = 1). Viable glandular tissue was found in specimens taken 18 and 36 months postoperatively. Other reported complications include lid malpositioning such as ptosis and entropium.

CONCLUSION: Transplantation of minor salivary glands is a promising new treatment option for severe dry eyes. The procedure is simple with minimal surgical risks. These grafts remain viable in over 90% and seem to be capable of sustaining a basal secretion for up to 36 months. Since experience with this technique is still very limited, prospective controlled studies have to be performed to establish the long-term survival of the glands and to characterise the salivary tear film and its impact on the ocular surface.

Abstract: Another literature-review type thing

Nothing particularly interesting in the abstract - literature review study, so the abstract is just generalizations. And quite frankly I'd be surprised if the list of "new applicable biological substances" is as exhaustive as what we have on DryEyeZone.

I like the highlighted comment, about no official guidelines replacing individual strategies, though I fear that in practice, there are 'unofficial' guidelines applied in most practices that tend to treat all dry eye patients alike regardless of what the real underlying problems are. (NPATS... Restasis... Lotemax... plugs. If that fails, then and only then do we consider something else. Sound familiar?)

Dev Ophthalmol. 2008;41:75-84.
Anti-inflammatory and immunosuppressive concepts.
Nölle B

BACKGROUND/PURPOSE: Patients with symptomatic dry eyes are frequently seen by every ophthalmologist. Understanding of the plethora of factors involved in sicca syndrome is essential to substantially help the patient. Besides important and frequent topical treatment options, anti-inflammatory and immunosuppressive systemic treatment concepts sometimes play an additional role.

MATERIAL AND METHODS: Relevant data of publications listed in Medline between 1966 and 2006 are analyzed.

RESULTS: Local treatment options are listed, immunosuppressive substances are shortly characterized with regard to action, side effects, and control parameters. An overview of new applicable biological substances is given.

CONCLUSIONS: A variety of treatment options can be offered to patients with dry eyes. The spectrum ranges from lubricants to systemical immunosuppressive substances. At present no official guidelines replace individual strategies to treat the patient. An escalation of treatment options has to be performed with individual experience.

Abstract: Sex hormones & tear lipocalin

Ah... this is a more like it. Hormone stuff. Very early stage enquiry but interesting... basically a step in the process of figuring out whether sex hormones control how much "tear lipocalin" (a tear component that dry-eyed folks tend to be low on) and if so, which and how... and all this just in bunnies. Gotta start somewhere though.

Sex hormone regulation of tear lipocalin in the rabbit lacrimal gland.
Exp Eye Res. 2008 Jul 22. [Epub ahead of print]
Seamon V, Vellala K, Zylberberg C, Ponamareva O, Azzarolo AM.

Tear lipocalin (TL) ( approximately 18kDa), a member of the lipocalin superfamily, has been identified as one of the major proteins present in rabbit lacrimal fluid. The concentration of TL has been found to be decreased in the tears of patients with dry eye disease. Lacrimal gland insufficiency, one of the major causes of dry eye disease, is known to affect mainly postmenopausal women, where there is a significant decrease in the production of androgen and estrogen. These observations suggest that sex hormones might influence dry eye indirectly by regulating the expression of TL. The purpose of this study was to determine: (1) the effect of sexual maturation on the expression of TL; and (2) if the expression of TL is regulated by the estrogen, 17beta-estradiol, and/or the androgen, dihydrotestosterone, in sexually mature female rabbits. Lacrimal fluid (LF) and lacrimal gland soluble fraction (Si) was collected from juvenile (2kg) and sexually mature (4kg) male and female New Zealand white (NZW) rabbits. In addition, LF and Si were collected from 4kg rabbits, 7days after being either sham operated (control), ovariectomized (OVX), ovariectomized treated with estrogen (OVX+E) or ovariectomized treated with dihydrotestosterone (OVX+DHT). Samples were analyzed for protein levels of TL by SDS-PAGE and Western blotting using a polyclonal rat anti-rabbit TL antibody. Densitometry analysis showed that TL protein levels in both LF and Si increased with age in male and female rabbits. In addition, TL protein levels were significantly higher in the sexually mature 4kg male compared with the 4kg female, while no significant difference in TL protein levels were seen among the juvenile male and female rabbits. Furthermore, ovariectomy decreased the protein levels of TL in LF and Si fraction by 50% and 20% respectively, compared with control values. Estrogen treatment increased TL protein levels by 30% and 50% in the LF and Si fraction respectively, compared with the sham operated group. DHT treatment also increased TL protein levels by approximately 150% in both LF and Si fraction compared with control values. These results support the hypothesis that sex hormones influence TL protein levels in rabbit lacrimal glands. The possibility of a role of TL in dry eye needs to be further investigated.

Abstract: Inflammatory stuff

Oh dear, oh dear, I'm feeling terribly uninspired today when it comes to summarizing & making sense of this sort of thing. Sometimes I just have to content myself with gathering dry eye related studies in one place and leaving the hard part (i.e. figuring out whether you should care) to y'all.

Interleukin-1 receptor-1-deficient mice show attenuated production of ocular surface inflammatory cytokines in experimental dry eye.
Cornea. 2008 Aug;27(7):811-7.
Narayanan S, Corrales RM, Farley W, McDermott AM, Pflugfelder SC.

PURPOSE: To compare inflammatory cytokine and defensin expression in response to experimental dry eye (EDE) in interleukin-1 receptor-1 (IL-1R1)-deficient (KO) mice with age-matched wild-type mice (WT).

METHODS: EDE was induced by subcutaneous scopolamine injection, exposure to low humidity, and an air draft for 5 days in 4- to 6-week-old KO and WT mice. Expression of cytokines IL-1 alpha, IL-1 beta, tumor necrosis factor (TNF)-alpha, IL-6, and mouse beta-defensins (mBD)-1, mBD-2, and mBD-3 was evaluated by real-time polymerase chain reaction in scraped corneal epithelial cells and whole conjunctival tissues. A multiplex bead assay was performed to quantitate IL-1 alpha, IL-2, IL-4, IL-10, interferon (IFN)-gamma, and TNF-alpha levels in tear fluid, and an enzyme immunoassay was used to quantitate IL-1 beta levels in tear fluid.

RESULTS: EDE significantly increased RNA transcripts for IL-1 alpha and beta in the conjunctiva and for TNF-alpha in the corneal epithelium of WT mice. Levels of IL-1 alpha, IL-1 beta, and IL-6 were significantly lower in the corneal epithelium and conjunctiva, and TNF-alpha was significantly lower in the cornea of KO mice after 5 days of EDE than WT mice. Tear fluid IL-1 alpha concentration increased above baseline on days 2-4 of EDE in WT and KO mice. A similar pattern was observed for tear TNF-alpha. Tear IL-1 beta increased throughout the 5 days of EDE in WT and KO mice. IFN-gamma, IL-2, IL-4, and IL-10 were undetectable in tear fluid of either strain before or after EDE. Corneal mBD-1 mRNA expression was unchanged and conjunctival mBD-1 transcripts decreased in WT and increased in KO mice with EDE. Untreated WT corneas, but not those of KO mice, expressed mBD-2 transcripts, whereas in the conjunctiva, mBD-2 increased in WT and decreased in KO mice with EDE. Corneal mBD-3 mRNA expression was undetected in WT mice, but increased after EDE in KO mice. Conjunctival mBD-3 transcripts were only detected in WT with EDE.

CONCLUSIONS: These findings indicate that IL-1 signaling is responsible in part for the increased expression of inflammatory cytokines and the changes in mBDs by the ocular surface tissues in response to desiccating stress. These results show the important regulatory aspects of IL-1 on ocular surface epithelial inflammation.

Abstract: Incontinentia pigmenti

Don't worry, I've never heard of it either ;)

Corneal abnormalities in incontinentia pigmenti: histopathological and confocal correlations.
Cornea. 2008 Aug;27(7):833-6.
Selvadurai D, Salomão DR, Baratz KH.

PURPOSE: To describe the clinical presentation and histopathologic and confocal correlations in a case of incontinentia pigmenti (IP)-associated whorllike corneal epitheliopathy.

METHODS: We describe the case report of a 22-year-old woman with IP and bilateral whorllike corneal epitheliopathy, with symptomatic dry eye complaints. Slit-lamp and confocal microscopic imaging confirmed that the pathology was restricted entirely within the epithelial layer. The cornea was debrided with the hopes of alleviating symptomatic eye complaints. The excised tissue was analyzed by standard light microscopy and transmission electron microscopy.

RESULTS: In vivo confocal microscopic imaging (ConfoScan 3; Nidek, Fremont, CA) of both eyes showed the presence of multiple bright, round objects approximately 7-20 microm in diameter and located entirely within the epithelial layer. Hematoxylin-eosin-stained sections of the debrided tissue showed a mild disorganization of the overall epithelial architecture. Transmission electron microscopy noted various degrees of degenerating nuclei. The corneal epithelial defect of the patient's left eye healed by the fourth postoperative day. The new epithelium appeared normal, but at the 1-month examination, there was recurrence.

CONCLUSIONS: Histomorphologic evaluation of the surgical specimen showed abnormal changes restricted to the epithelium in our patient. The observed changes are suggestive of a primary abnormality of cell maturation, which results in degeneration, and apoptosis as the epithelial cells migrate upward. The rapid recurrence of keratopathy clearly indicates that supportive treatment of blurred vision and secondary superficial punctate keratopathy with artificial tears, punctal plugs, and bandage contact lens are more likely to be beneficial.

Abstract: Fluid mechanics...

Scientific stuff....

A new look at lubrication of the ocular surface: fluid mechanics behind the blinking eyelids.
Ocul Surf. 2008 Apr;6(2):79-86.
Cher I.

The concept of the dacruon was presented by the author in this journal in July 2007. Dacruon, defined as "the body of unshed fluid, constantly occupying the ocular surface sac [OSS], comprising the mucoaqueous pool [MAP] and its covering lipid sealant," prompts a fresh consideration of OSS lubrication. The author notes scientific agreement that in the preocular, interpalpebral OSS (the menisco-optical domain), the mucous gel of the MAP adheres to subjacent bulbar epithelium. In the retropalpebral recesses (the "lubrication domain"), lid and globe epithelia are juxtaposed. The author proposes that microvilli and glycocalyx "grasp" the bases of dacruon mucous gels, enabling lid and globe to "drive" fluid movement. The adherent gels and associated low viscosity mucous modules mitigate friction. There is no substantive lipid layer. The modules abut, "mirror-image" fashion, forming an interface concentric with the eyeball surface about midway between the palpebral and bulbar mucosae. Here, kinetic energy originating from both lid and globe has been progressively dissipated by fluid friction, residual movement reduced to creeping flow. Shear stress is displaced from the rapidly moving epithelia, to occur between the more remote, slow-moving midzone fluids, minimizing frictional blink-related microtrauma. The midway interface serves as a "slip interface," crucial to the mucoaqueous lubrication of the OSS. Concomitantly, the OSS also forms the anterior lubricating compartment of the "ball and socket" ocular joint.

Medical news: Ophthalmologists should be involved before eyelid surgery

Yes, yes, yes!!! The more awareness about this we can get among plastic and oculoplastic surgeons the better.

The gist of the report - well, of the part I'm interested in - is that people getting eyelid surgery by a plastic surgeon really need an ophthalmologist involved in evaluation and surgical planning... Dry eye risk from changes to the lids being of course a key consideration especially in anyone who already has dry eye and/or who has had laser eye surgery.

Ocular Surgery News, August 2008
Preop exams by ophthalmologists urged before oculoplastic surgery

Dr. Lucchini said plastic surgeons who operate on the eye should evaluate the patient’s visual function, even in simple ways such as covering, in turn, one of the patient’s eyes and asking him or her to look at distant objects. In cases of evident or suspected visual defects, a more professional evaluation by an ophthalmologist is advisable.

“Evaluating and documenting preoperative vision protects the surgeon from any medical-legal accusation of having compromised the patient’s visual function,” he said.

Tear film integrity should also be assessed, taking into account that about 20% of the population in Europe and the United States suffer from some kind of tear film alteration because of contact lens use, allergies or systemic disorders such as Sjögren’s syndrome.

“Tear film dysfunction is one of the most common causes of patient dissatisfaction or discomfort following eyelid surgery,” Dr. Lucchini said. “Patients often complain of dry eyes and burning sensations. This most often comes from a preoperative alteration of the tear film, which has been worsened or made symptomatic by the operation because, for some time after surgery, the eyes don’t close properly.”

A Schirmer’s test performed preoperatively will show if the tear production is normal, and the patient’s history will provide additional information on potential causes of tear film alterations.

“Patients who are taking antidepressants or benzodiazepines … may have alterations, both in the quantity and quality of tears,” he said.

Also, contact lens wearers, particularly those who show signs of contact lens intolerance, are likely to have an abnormal tear secretion.

In patients who have previously undergone corneal refractive surgery, whether surface ablation or LASIK, tear production is altered for 1 year or more after the treatment, Dr. Lucchini said.

“These are not necessarily exclusion criteria, but just a warning that some problems may occur over the first weeks following oculoplasty. Patients should be made aware of this possibility before they sign their consent,” he said.

Incidentally, this was kind of an interesting quote - it is certainly in agreement with my experience of all the surface ablation patients we get on the bulletin boards, though it's directly at variance with how ASA is marketed these days:

In patients who have previously undergone corneal refractive surgery, whether surface ablation or LASIK, tear production is altered for 1 year or more after the treatment, Dr. Lucchini said.