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PubMed2004

Doxycycline-a role in ocular surface repair.

BACKGROUND/AIMS: Doxycycline is a broad spectrum antibiotic that chelates metal ions and is frequently used as part of the treatment of ocular surface diseases. Its therapeutic value has been ascribed to an ability to inhibit matrix metalloproteinase (MMP) activity and both MMP and IL-1 synthesis. The aim of this study was to evaluate the role of doxycycline as an inhibitor of corneal MMPs and assess its contribution to ocular surface repair mechanisms. METHODS: Corneal epithelial cell and keratocyte cultures were grown to confluence and incubated with IL-1alpha, LPS, doxycycline, or doxycycline and LPS in serum free medium for 4 days. The cells were either harvested and assayed for caspase-3 activity or stained with either AE5 or antivimentin antibodies. Media samples were concentrated and assayed for MMP activity by zymography or using a fluorigenic substrate. ELISA was used to quantify IL-1alpha, MMPs -1,-2,-3,-9, and TIMPs -1 and -2. RESULTS: IL-1alpha and LPS had no effect on MMP/TIMP production by cultured corneal epithelial cells and keratocytes. Corneal MMP-2 inhibition by doxycycline was partially [Ca(2+)] dependent but irreversible. At the minimum inhibitory concentration, 100 micro m, doxycycline had no apparent effect on MMP and TIMP production, but ultimately caused the death of keratocytes and some of the epithelial cells that detached from their basement membrane. Caspase-3 activity was not detected in dead or dying keratocytes. The mechanism of cell death in cultured corneal epithelial cells was not caspase-3 related apoptosis as the activity of this enzyme, normally detectable, was lost. The epithelial cells that survived doxycycline treatment did not bind antivimentin antibody and compared with controls, reacted less with the AE5 antibody. They were probably transient amplifying cells. CONCLUSIONS: Doxycycline irreversibly inhibits corneal MMP-2 activity by chelating the metal ions that are catalytically and structurally essential. Corneal MMP/TIMP production in vitro is not modulated by IL-1alpha, LPS, or doxycycline. The therapeutic value of doxycycline may depend upon its effective concentration at the ocular surface and probably relates to its chelating properties.

Anti-Bacterial Agents↗

PubMed1995

Biological activity of N-(4-hydroxyphenyl) retinamide-O-glucuronide in corneal and conjunctival cells of rabbits and humans.

Previous studies of topical retinoic acid for treatment of ocular surface disease met with limited success due to instability and irritancy of the retinoid and lack of efficacy in keratoconjunctivitis sicca. There has, however, been continued interest in the treatment of mucin deficiency and cicatrizing conjunctival diseases, such as ocular cicatricial pemphigoid (OCP), topically with retinoids. In this study the biological activity of stable, water-soluble, synthetic retinoid, N-(4-hydroxyphenyl) retinamide-O-glucuronide (4-HPROG) was investigated in vivo and in vitro using conjunctival and corneal epithelium and fibroblasts. Vitamin A-deficient rabbits with stage 3-4 corneal xerosis and squamous metaplasia confirmed by conjunctival impression cytology were treated with topical 0.1% 4-HPROG in an artificial tear vehicle for 3 weeks. Impression cytology was repeated at 2 and 3 weeks and at 3 weeks conjunctival biopsies were fixed for histology. Growth curves were generated using conjunctival fibroblasts of rabbits and humans (normals and patients with cicatrizing conjunctival disease including OCP and Stevens-Johnson syndrome) cultured in the 10(-8)-10(-6) M 4-HPROG. In vivo, corneal xerosis cleared in three days. A normal conjunctival epithelium was restored by 2 weeks and goblet cells were present by 3 wk, with no change in vehicle-treated controls. No ocular irritation occurred. In vitro, 10(-6) M 4-HPROG inhibits growth of rabbit conjunctival fibroblasts. The retinoid had no effect on proliferation of conjunctival fibroblasts from normal humans but the doubling time of cells from patients with OCP increased significantly, from 50.9 +/- 10.01 h (control) to 61.5 +/- 8.95 h (retinoid). Proliferation of conjunctival fibroblasts from a patient with Stevens-Johnson syndrome was also inhibited. N-(4-hydroxyphenyl) retinamide-O-glucuronide is biologically active and merits further study to determine its efficacy in controlling conjunctival fibrosis and treating ocular surface squamous metaplasia.

Animals↗

PubMed2006

In vivo confocal microscopy and ex vivo flow cytometry: new tools for assessing ocular inflammation applied to rabbit lipopolysaccharide-induced conjunctivitis.

PURPOSE: Lipopolysaccharide (LPS) may act as a key stimulatory agent in ocular surface diseases (OSDs) through TNF-alpha release. We used in vivo confocal microscopy (CM) and ex vivo flow cytometry, two new tools for assessing ocular inflammation induced by LPS. METHODS: We investigated a model of acute inflammation in rabbits by subconjunctival injection of LPS and developed new evaluation techniques for animal models: CM, to observe inflammatory infiltrates, and conjunctival impression cytology (IC) specimens processed with in vitro CM and flow cytometry for assessing TNF-alpha and TNF receptor-1 (TNFR-1) expression. A neutralizing anti-TNF-alpha antibody was used to assess the role of TNF-alpha. RESULTS: In vivo CM provided high-resolution images of inflammatory infiltrates and leukocyte rolling in blood vessels. It showed that the LPS group presented strong conjunctival inflammation, reaching its maximum level 4 h after injection. Flow cytometry and immunostaining in IC specimens showed an increased expression of TNF-alpha and TNFR-1 in the epithelium. Immunohistology confirmed these results and showed infiltration of vimentin+, CD4(+), and CD8(+) cells in the conjunctiva. TUNEL-positive cells were found 4 h after injection. Neutralizing anti-TNF-alpha significantly inhibited LPS-induced inflammation and apoptosis evaluated by in vivo CM; and inhibited LPS-induced TNF-alpha and TNFR-1 expression by ex vivo conjunctival IC specimens evaluated by flow cytometry. CONCLUSIONS: IC specimens and new-generation in vivo CM were thus in good agreement with immunohistology and appeared to be reliable, effective, and nonharmful methods to investigate experimental models of OSDs. The two new tools applied here evaluate the animal models in vivo on the cellular lever. This study is consistent with the experimental research's strategy by reducing the number of experimental animals used.

Animals↗

PubMed2006

Ketorolac during the induction phase of cyclosporin-A therapy.

PURPOSE: The aim of this study was to determine if the concomitant use of ketorolac 0.4% and cyclosporin-A improves patient comfort during the induction phase in treating chronic dry eye disease. METHODS: Patients (n = 52) with clinically diagnosed dry eye were randomized to receive either cyclosporin-A monotherapy twice-daily (BID) or a BID adjunctive regimen of ketorolac, followed by the instillation of cyclosporin-A 10 min later. Study visits were at baseline, week 2, and week 6. At each study visit, patients underwent an evaluation for corneal staining, Schirmer's scores, and tear break-up time tests. Patients were asked to rate ocular comfort on a 4-point scale and to complete the ocular surface disease index (OSDI). Changes from baseline readings were recorded at week-2 and week-6 visits, and final patient success on treatment regimen was evaluated at week 6. RESULTS: After 6 weeks, the mean ocular comfort score of adjunctive patients improved 2.55 +/- 0.95 points, versus 1.53 +/- 0.91 points for monotherapy (P = 0.309). The adjunctive regimen provided significantly greater corneal staining reductions versus monotherapy, mean reduction in staining of 1.74 +/- 0.9, versus 1.27 +/- 0.56 (P = 0.044). CONCLUSIONS: Concurrent ketorolac 0.4% use with cyclosporin-A significantly reduced corneal staining and increased comfort in the induction phase.

Aged↗

PubMed2001

[Ex-vivo expansion of cornea stem cells. Experimental principles and initial clinical results].

The ocular surface epithelium is composed of conjunctiva, limbus and cornea. These three compartments and an stable preocular tear film are crucial factors determining ocular surface health. Stem cells of the corneal epithelium are exclusively located at the limbus. Limbal stem cells are the ultimate source of regeneration of the entire corneal epithelium and in a variety of ocular surface diseases limbal stem cell deficiency has been observed to be a characteristic feature. Therefore renewal of the limbal stem cell population using different surgical techniques has been described as the only possible therapeutic strategy. Recent advancements in cell biology have enabled the development of new models of tissue engineering as a tool for tissue replacement. The aim of this review is to summarize recently reported clinical and experimental studies showing new developments in tissue engineering for the reconstitution of the ocular surface epithelium.

Animals↗

PubMed2000

Efficacy and safety of cyclosporin A ophthalmic emulsion in the treatment of moderate-to-severe dry eye disease: a dose-ranging, randomized trial. The Cyclosporin A Phase 2 Study Group.

OBJECTIVE: To investigate the efficacy, safety, formulation tolerability, and optimal dosing of a novel cyclosporin A oil-in-water emulsion formulation for the treatment of moderate-to-severe dry eye disease. DESIGN: Randomized, multicenter, double-masked, parallel-group, dose-response controlled trial. PARTICIPANTS: Total enrollment: 162 patients; cyclosporin A groups: 129 patients; vehicle group: 33 patients. INTERVENTION: Patients instilled study medication (cyclosporin A ophthalmic emulsion 0.05%, 0.1%, 0.2%, or 0.4%, or vehicle) twice daily into both eyes for 12 weeks, followed by a 4-week posttreatment observation period. MAIN OUTCOME MEASURES EFFICACY: rose bengal staining, superficial punctate keratitis, Schirmer tear test, symptoms of ocular discomfort, and the Ocular Surface Disease Index (OSDI; a measure of symptom frequency and impact on vision-related functioning). SAFETY: biomicroscopy, cyclosporin A blood levels, conjunctival microbiology, intraocular pressure, visual acuity, and monitoring of adverse events. RESULTS: In a subset of 90 patients with moderate-to-severe keratoconjunctivitis sicca, the most significant improvements with cyclosporin A treatment were in rose bengal staining, superficial punctate keratitis, sandy or gritty feeling, dryness, and itching, with improvements persisting into the posttreatment period in some treatment groups. There was also a decrease in OSDI scores, indicating a decrease in the effect of ocular symptoms on patients' daily lives. There was no clear dose-response relationship, but cyclosporin A 0.1% produced the most consistent improvement in objective and subjective end points and cyclosporin A 0.05% gave the most consistent improvement in patient symptoms. The vehicle also performed well, perhaps because of its long residence time on the ocular surface. There were no significant adverse effects, no microbial overgrowth, and no increased risk of ocular infection in any treatment group. The highest cyclosporin A blood concentration detected was 0.16 ng/ml. All treatments were well tolerated by patients. CONCLUSIONS: Cyclosporin A ophthalmic emulsions, 0.05%, 0.1%, 0.2%, and 0.4%, were safe and well tolerated, significantly improved the ocular signs and symptoms of moderate-to-severe dry eye disease, and decreased the effect of the disease on vision-related functioning. Cyclosporin A 0.05% and 0.1% were deemed the most appropriate formulations for future clinical studies because no additional benefits were observed with the higher concentrations.

Adult↗

PubMed1998

The exposed ocular surface and its relationship to spontaneous eyeblink rate in elderly caucasians.

The purpose of this study was to assess spontaneous eyeblink activity in the primary eye position, and its relationship to the exposed ocular surface area in elderly individuals without significant ocular surface disease. Spontaneous eyeblink frequency (SEBF) was assessed for a group of Caucasians aged 61 to 81 years, by videography in silence over a 5 min period; inter-blink interval (IBI), the maximum inter-blink interval (mIBI) and the modal eyeblink frequency (mEBF) were derived from video recordings. The ocular surface area was calculated from video-planimetry using different formulae. The average palpebral aperture was 8.3 +/- 2.3 mm (n = 45, +/- S.D.), resulting in an average exposed area of 1.13-2.13 cm2 depending on the formula used; the preferred estimate was 1.25 cm2. A highly significant relationship (P < 0.001, r2 = 0.835) was found between time-averaged palpebral aperture (p) and exposed ocular surface (A = 0.244p-0.763). An average SEBF of 11.9 blinks min-1 was measured (range 0.8-43.6). No correlation (P > 0.35, r2 < or = 0.01) was found between SEBF, IBI, mIBI, or mEBF and the palpebral aperture or the exposed surface area, regardless of the formulae used. The exposed ocular surface area per se does not appear to be an important determinant of spontaneous eyeblink activity in elderly Caucasians.

Aged↗

PubMedDate not supplied

Measuring the lacunar sulci as a new indicator of shrinkage of the ocular surface.

PURPOSE: To present a new indicator that measures the sulci of the lacrimal lake of the eye according to the degrees of ocular abduction at which they vanish. This new approach will help determine the severity and progression of mucosal retraction in ocular surface diseases. METHODS: A total of 181 eyes of 94 healthy persons, 130 eyes of 65 patients with Sjogren's syndrome, and 30 eyes of 15 patients with ocular pemphigoid were examined using the slit lamp. We recorded the vanishing point of the three main lacunar sulci (plico-bulbar, plicocaruncular and dermo-caruncular) while abducting. RESULTS: In healthy persons, the average vanishing points for the first and second lacunar sulci were respectively, 53.20 +/- 12.3 and 54.50 +/- 9.8. In patients with Sjogren's syndrome, 49.53 degrees +/- 10.81 and 53.17 degrees +/- 7.28 and in patients with incipient ocular cicatricial pemphigoid, 42.69 degrees +/- 14.33 and 44.46 degrees +/- 16.85. Statistical significance was p < 0.005. CONCLUSIONS: The lacunar sulci are shallower and vanish sooner in ocular cicatricial pemphigoid and Sjogren syndrome than in normals. Investigating the vanishing point of the lacunar sulci while abducting is useful for grading the shrinkage of the conjunctiva, caruncle and medial canthus.

Adult↗

PubMed1999

Reflective meniscometry: a non-invasive method to measure tear meniscus curvature.

AIMS: To devise a method to measure tear meniscus curvature by a non-invasive specular technique. METHODS: A photographic system was devised. The system consisted of a camera and an illuminated target with a series of black and white stripes oriented parallel to the axis of the lower tear meniscus. The target was mounted on a flash gun close to the objective of a Brown macrocamera and calibrated using a graduated series of glass capillaries of known diameter, ground down to expose the inner wall. It was then applied to normal human eyes (n = 45) to measure the tear meniscus curvature. A video system was also assessed which provided qualitative online information about the tear meniscus. RESULTS: Using the photographic system, measured values for capillary radii were in excellent agreement with theoretical calculations (r2 = 0.996, p < 0.0001). The radii of curvature of lower tear menisci in normal human subjects (mean 0.365 (SD 0.153) mm, range 0.128-0.736; n = 45) were similar to those reported in the literature. Both systems demonstrated variations in meniscus shape. The video system provided stable images of human menisci over prolonged periods of time and promises to be useful for the analysis of dynamic changes in meniscus volume. CONCLUSIONS: Reflective meniscometry is a non-invasive technique providing quantitative information about tear meniscus shape and volume and of potential value in the study of ocular surface disease.

Calibration↗

PubMed2004

Punctal occlusion in the management of chronic Stevens-Johnson syndrome.

PURPOSE: To evaluate the effect of lacrimal punctal occlusion in the management of the ocular surface disease in chronic Stevens-Johnson syndrome. DESIGN: Retrospective noncomparative case series. PARTICIPANTS: Thirty-one eyes of 18 patients with chronic Stevens-Johnson syndrome seen at the Department of Ophthalmology of the Tokyo Dental College were studied. INTERVENTION: Patients' lacrimal puncta were occluded by cauterization or with punctal plugs. MAIN OUTCOME MEASURES: The effect of lacrimal punctal occlusion was evaluated by changes in subjective symptoms, best-corrected visual acuity (VA), Schirmer test, tear clearance test, and ocular surface double vital staining before and after punctal occlusion. RESULTS: After lacrimal punctal occlusion, symptomatic improvement was observed in 19 eyes (61.3%). The mean logarithmic VA showed significant improvement from -0.64+/-0.87 to -0.52+/-0.86 (P<0.05). The Schirmer I test results before punctal occlusion yielded a mean score of 7.4+/-8.7 mm, which changed to 10.2+/-8.3 mm after punctal occlusion. The mean preocclusion and postocclusion tear clearance values were 7.5+/-6.6 times and 4.9+/-4.8 times, respectively. The Rose Bengal staining score decreased from 4.7+/-2.8 to 2.7+/-2.2 points (P<0.05), and the fluorescein staining score decreased from 5.0+/-2.3 to 2.2+/-2.5 points (P<0.05), respectively. CONCLUSIONS: Concurrent improvements in subjective symptoms, vital staining scores, and VA point to the favorable effects of lacrimal punctal occlusion for the ocular surface health in chronic Stevens-Johnson syndrome.

Adolescent↗

PubMed1999

A novel mechanism for benign essential blepharospasm.

PURPOSE: The purpose of this study is to test the hypothesis that the photophobia of benign essential blepharospasm (BEB) is caused by sympathetically maintained pain. METHODS: Nineteen patients with photophobia and BEB were enrolled in an unblinded prospective treatment trial. The intervention was blockade of the superior sympathetic ganglion with local anesthetic. Outcome measures included the patient's subjective report of ocular surface dryness, foreign body sensation, and eyelid spasm. We also obtained video recordings of eyelid movements. RESULTS: Of the 19 patients, 13 reported subjective improvement in BEB symptoms after cervical sympathetic blockade (CSB). Thirteen of 19 patients also had objective evidence of decreased light-induced eyelid spasm after CSB. Ocular surface disease was present in 18 of 19 patients. CONCLUSION: These data support the hypothesis that in many patients with BEB there is a sympathetically maintained pain syndrome associated with external ocular disease. We speculate on a neurologic circuit that may explain these findings.

Anesthetics, Local↗

PubMed2004

Development of cultivated mucosal epithelial sheet transplantation for ocular surface reconstruction.

Regenerative medicine via tissue engineering is a newly developed medical field based on the use of somatic stem cells to generate biological substitutes and improve tissue functions. The achievement of these objectives depends on two important factors: stem cells, which are high in proliferability and differentiability, and the substrates that support them. In order to reconstruct the ocular surface in patients with severe ocular surface diseases, we decided to investigate the feasibility of human amniotic membrane as an epithelial carrier, and found that denuded amniotic membrane was the most appropriate substrate for this purpose. To develop the surgical treatment using denuded amniotic membrane as a carrier, we established the tissue engineering system for making transplantable epithelial sheets of either corneal or oral mucosal epithelial cells for ocular surface reconstruction.

Amnion↗

PubMed2005

Current concepts and techniques in keratoprosthesis.

PURPOSE OF REVIEW: Diseases affecting the cornea are a major cause of blindness worldwide, second only to cataract in overall importance, with an estimated 10 to 15 million affected people. Although keratoplasty is by far the most successful transplantation surgery, the outcomes in high-risk adult patients, including those with ocular surface diseases and multiple graft rejections, and in pediatric patients with congenital corneal opacities are disappointing. RECENT DEVELOPMENTS: Regrettably, no significant clinical developments have been achieved in the field of corneal transplantation since the introduction of steroids for graft rejection. Furthermore, obtaining donor corneal tissues and eye banking, particularly in the developing countries where corneal blindness is most prevalent, are problematic. Although the postoperative complications may be severe and limit the use of currently available devices, keratoprosthesis--artificial corneal implantation--has a role in the management of corneal blindness in carefully selected patients with complex ocular diseases who are at high risk for graft failure. SUMMARY: This article reviews the recent ophthalmic literature published on the current concepts and techniques of keratoprosthesis surgery.

Artificial Organs↗

PubMed1990

[The dry eye. Status determination and prospects].

Dry eye is the most common cause of chronically red, irritated eyes. Thus, in cases of chronic conjunctivitis dry eye must be excluded. The noncritical use of vasoconstrictive eye drops and/or corticosteroids is obsolete. Up to now the diagnosis of dry eye has been based on a combination of the patient's history, slit-lamp examination, determination of tear film break-up time, the Schirmer test and basic secretion test. Unfortunately, there is enormous deviation in all of these tests, which means that they provide poor diagnostic reliability. Dry eyes are rarely associated with systemic diseases, e.g. Sjogren's syndrome. This autoimmunological disease is often first diagnosed by the ophthalmologist. Quantitative or qualitative deficiencies of one or more layers of the complex tear film can result in dry eyes, but inflammatory agents or primary ocular surface diseases may also be involved. Within the next few years analyses of tear-film proteins, toposcopy, tear-film fluorophotometry, impression cytology and corneal epithelial fluorophotometry may prove to be reliable tests for the detection of dry eye. The improved mucomimetic quality of artificial tears, the avoidance of toxic preservatives, tear production stimulants (eloisin, physaelamin), fibronectin or the epithelial growth factor may facilitate the management of dry eye.

Conjunctiva↗

PubMed1997

Ocular flora of patients with AIDS compared with those of HIV-negative patients.

PURPOSE: To determine whether there are quantitative or qualitative differences in the ocular flora of patients with acquired immunodeficiency syndrome (AIDS) compared with human immunodeficiency virus (HIV)-negative patients. METHODS: Forty patients with AIDS and 42 HIV-negative controls were sex and age matched. All subjects had a detailed anterior segment examination, including Schirmer's test, rose bengal staining, and quantitative cultures of the conjunctiva and lids. Statistical evaluation of the relation between AIDS, keratoconjunctivitis sicca (KCS), and ocular flora was performed. RESULTS: No differences were observed in the types or numbers of organisms isolated from the conjunctiva or lids of patients with AIDS and HIV-negative subjects. Ocular flora was not influenced by use of systemic antibiotics, level of immunosuppression as measured by CD4 lymphocyte counts, KCS, or other ocular-surface disease. One AIDS patient was colonized by large numbers of Haemophilus influenzae OU with minimal clinical signs of inflammation or infection. CONCLUSION: There do not appear to be any differences in the ocular flora of HIV-negative patients and patients with AIDS. Presence of KCS and level of immunosuppression do not appear to affect the ocular flora in patients with AIDS.

Acquired Immunodeficiency Syndrome↗

PubMed2001

Therapeutic use of Bausch & Lomb PureVision contact lenses.

PURPOSE: To evaluate the Bausch & Lomb PureVision contact lens as a continuous wear contact lens for therapeutic indications in a prospective open-ended non-randomized clinical trial. METHODS: Patients with a variety of corneal and ocular surface disease conditions presenting at the Singapore National Eye Centre who required therapeutic continuous contact lens wear were enrolled. Therapeutic indications included pain relief, corneal protection, and enhancement of corneal wound healing. Success or failure of specific treatment indications was assessed in all cases, with evaluation of lens performance and fit characteristics, and the presence of ocular complications or lens-related complications was noted. RESULTS: There were 54 patients (54 eyes), and the mean duration of continuous contact lens wear was 1.1 months. Conditions treated included post-surgical indications (n = 36) (post-keratoplasty or ocular surface transplantation, post-LASIK or PRK surgery) bullous keratopathy (n = 7), chemical burns (n = 3), epithelial abrasions or recurrent corneal erosion syndromes (n = 3), corneal perforations (n = 3), neurotrophic ulcer (n = 1), and corneal laceration (n = 1). For the indication of corneal healing (40 eyes), improved healing was noted in 38 eyes (96%), with full healing occurring in 33 eyes (83%). For pain relief (28 eyes), 27 patients (96%) had considerable or complete pain relief, and the remaining patient reported partial pain relief. For corneal protection (21 eyes), lens wear was fully protective in all cases. The lens performance and fitting characteristics surpassed any previous therapeutic lenses used by the investigators. Complications related to contact lens wear were limited to one case of a culture-negative corneal infiltrate requiring cessation of therapeutic lens wear and one case of a loosely fit lens. CONCLUSIONS: Our results show that the PureVision contact lens exhibits good safety and efficacy when utilized as a continuous wear therapeutic lens. With the theoretical advantage of increased oxygen transmissibility reducing the risk of hypoxia-related complications, this new lens may be one step closer to the ideal therapeutic contact lens. The PureVision contact lens is now our primary bandage lens of choice in our corneal, external disease, and refractive surgery services.

Adolescent↗

PubMed1996

Initial treatment of microbial keratitis.

PURPOSE: The common occurrence of failed medical treatment in microbial keratitis led us to investigate this phenomenon. METHODS: We retrospectively reviewed all ulcers that presented to our department for 24 consecutive months. We classified each ulcer as either a therapeutic success or failure based on a precise definition of the response to initial antibiotic selection. We then analyzed multiple factors including: antibiotic selection, ophthalmic disease, ulcer characteristics, and management, to determine their significance in the success or failure in treating microbial keratitis. Complications were also examined. RESULTS: Important factors in failure were non-fortified antibiotics (P < 0.001), ocular surface disease (P = 0.0178) and outpatient management (P < 0.001). Large ulcers (P = 0.051) were of borderline significance. Sensitivity results reflect high sensitivity among successfully treated patients when appropriate antibiotics are chosen. CONCLUSIONS: This report provides insight into current practice patterns and potential means to improve success in managing microbial keratitis.

Ambulatory Care↗

PubMed2001

[Cyclosporin A eyedrops: manufacturing, toxicity, pharmacokinetics and indications in 2000].

INTRODUCTION: Cyclosporin eye-drops allow local immunoregulation without systemic side effects and is an alternate to local steroids. In this article we review specific problems of product setup and clinical studies published over the past 20 years. PRODUCT SETUP: The main problems in eye-drop preparation are sterility, pH, particles, and its lipophilic properties. Numerous excipients have been tested including oil solvents, alphacyclodextrin, collagen shields, liposomes, polyester nanocapsules, but documentation on stability of the molecule is inadequate. TOXICITY: Epithelial toxicity is well known and is probably mainly due to the excipient. No endothelial toxicity has been described in vivo. Repeated doses lead to uveal reactions in animals, which could limit the indications for intraocular diseases. PHARMACOKINETICS: Bioavailability is mainly limited by the lipophilic properties. Oil excipients, the most widely used, lead to good corneal penetration but low intraocular concentrations. Cyclosporin bioavailability is improved when using hydrophilic excipients. INDICATIONS: Every ocular surface disease that involves cytokines is a potential indication for cyclosporine eyedrops: keratoconjunctivitis sicca, vernal keratitis, adjuvant therapy of filtering surgery, stromal herpes keratitis, immunity limbal keratitis, and Thygeson's keratitis. There is biological evidence of efficacy, and encouraging results from many studies, yet few have tested a large number of patients. A large multicenter study on dry eye is currently in progress.

Biological Availability↗