Chronic Ocular Surface Disease Research Articles

Prosthetic Replacement of the Ocular Surface Ecosystem Treatment for Ocular Surface Disease in Pediatric Patients With Stevens-Johnson Syndrome

To report the outcomes of prosthetic replacement of the ocular surface ecosystem (PROSE) treatment in pediatric patients with chronic ocular surface disease associated with Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN). Retrospective, interventional case series. Patients aged 18 years or younger seen in consultation for PROSE treatment at a single center between January 1992 and December 2016 with a history of SJS/TEN were reviewed. Demographics, etiology of SJS/TEN, age at treatment milestones, best-corrected visual acuity (BCVA) at treatment milestones, and treatment failures were recorded. BCVA at the initial presentation visit was compared to BCVA at the time of PROSE device dispense and at the last recorded visit. Twenty-seven female and 22 male patients were reviewed. Reported etiology was antibiotic (n= 19), antiepileptic (n= 9), antipyretic (n= 9), other (n= 3), and unknown (n= 9). The mean age was 6.4 years at disease onset and 9.3 years at time of initial presentation. The mean duration of follow-up was 5.45 years. The median BCVA at the initial presentation was 0.6 logMAR (20/80 Snellen), and was significantly improved to 0.18 logMAR (20/30 Snellen) at the time a PROSE device was dispensed (P < .0001). The median BCVA at the last recorded visit was significantly improved to 0.18 logMAR (20/30 Snellen, P= .0004). There were 15 patients who failed PROSE treatment (30.6%). PROSE treatment is feasible in over two thirds of pediatric patients with chronic ocular surface disease related to SJS/TEN and results in significant improvement in vision that is durable over a period of many years.

Genetic diversity and persistent colonization of Enterococcus faecalis on ocular surfaces.

Enterococcus faecalis causes severe acute endophthalmitis and often leads to poor visual outcomes. Conjunctival bacterial cultures occasionally grow atypical bacteria including E. faecalis, which can potentially contribute to the development of postoperative endophthalmitis. However, the characteristics of these ocular E. faecalis strains are unknown. This study is the first attempt to determine the population characteristics of E. faecalis clinical isolates from eye infections and ocular commensals. Retrospective METHODS: Twenty-eight E. faecalis ocular isolates were collected from 23 patients at 3 referring hospitals. The multilocus sequence typing (MLST) data were analyzed using the eBURST program. Phenotypes of cytolysin and gelatinase, antibiotic susceptibility, and mutations of the quinolone resistance-determining regions (QRDRs) of gyrA and parC were also examined. Pulsed-field gel electrophoresis (PFGE) was performed for strains from the same patients. PFGE revealed that 3 patients retained identical strains for 10 months to 2 and a half years. MLST identified 12 sequence types (STs), which were clustered into 3 clonal complexes (CCs) and 8 singletons, with ST179 the largest. Thirteen of the 23 isolates (56.5%) belonged to CC58, CC8, or CC2, which have previously been reported to be major CCs. Six of the 23 strains (26.0%) exhibited high-level quinolone resistance derived from mutations of the QRDRs in both gyrA and parC. The sequence types of E. faecalis ocular isolates were divergent, with no eye-specific lineages observed. Persistent colonization of E. faecalis on the ocular surface was demonstrated in patients with chronic ocular surface diseases.

Dysregulated Marginal Zone B Cell Compartment in a Mouse Model of Sjögren’s Syndrome with Ocular Inflammation

The risk of developing lymphoma in patients with Sjögren’s syndrome (SS) is 44 times higher than in the normal population with the most common lymphomas derived from marginal zone B (MZB) cells. Current understanding of the role of MZB cells in SS is primarily based on salivary gland pathology, while their contextual association with lacrimal glands and ocular manifestations largely remains unknown. We examined this possibility using a SS mouse model (thrombospondin-1 deficient (TSP1−/−)) with well-characterized ocular disease. We determined the frequency, localization, and cytokine profiles of MZB cells and their association with an antibody response in TSP1−/− mice treated with a TSP-derived peptide. A significantly increased frequency of MZB cells was detected in the spleens and lacrimal glands of TSP1−/− mice in comparison to wild-type tissues as detected by immunostaining. An altered cytokine profile of TSP1−/− MZB cells was supportive of T helper 17 (Th17)-related pathogenesis. A significantly reduced antibody response and the splenic MZB compartment against an eye-derived antigen were noted in TSP-derived peptide-treated mice. These changes correspond with the previously reported ability of the peptide to ameliorate SS-related ocular manifestations. Collectively, our results demonstrate dysregulation of MZB cells in TSP1−/− mice and highlight their role in the context of SS-related chronic ocular surface disease.

Elevated Aqueous Cytokine Levels in Eyes With Ocular Surface Diseases

To evaluate cytokine and protein levels in the aqueous humor (AqH) of eyes with ocular surface diseases. Prospective consecutive case series. This study includes 14 patients (aged 62.4 ± 13.7 years) with chronic-phase ocular surface diseases (4 with ocular cicatricial pemphigoid, 5 with chemical burns, 2 with a thermal burn, 2 with Stevens-Johnson syndrome, and 1 with exposure keratitis), 14 matched patients without ocular surface disease (controls with corneal scar), and 30 patients who underwent cataract surgery (healthy controls). AqH samples were collected at the beginning of surgery. AqH levels of cytokines (interleukin [IL]-1α, IL-1β, IL-4, IL-6, IL-8, IL-10, IL-12p70, IL-13, IL-17A, monocyte chemotactic protein [MCP]-1, interferon [IFN]-α, IFN-γ, macrophage inflammatory protein [MIP]-1α, MIP-1β, P-selectin, E-selectin, soluble-intercellular adhesion molecule [s-ICAM]-1, tumor necrosis factor [TNF]-α, granulocyte-macrophage colony-stimulating factor [GM-CSF], IFN-γ-induced protein [IP]-10) were measured using multiplex beads immunoassays. The levels of IL-6, IL-10, IL-17A, GM-CSF, E-selectin, P-selectin, and s-ICAM in AqH were significantly elevated in eyes with ocular surface diseases (in pg/mL: 1696 ± 804, 4.0 ± 1.0, 24.3 ± 9.8, 26.0 ± 18.3, 5150 ± 1232, 13122 ± 7219, and 7914±2813, respectively), compared to healthy controls (IL-6: 6.36 ± 0.94, P= .001; IL-10: 1.68 ± 0.04, P=.0006; IL-17A: 3.7 ± 0.2, P= .008; GM-CSF: 2.7 ± 0.3, P= .007; E-selectin: 2093 ± 37, P=.0001; P-selectin: 3658 ± 137, P= .0001; sICAM-1: 1397 ± 119, P= .008). The levels of IL-6, IL-17A, E-selectin, and P-selectin in AqH were significantly higher in eyes with ocular surface diseases compared to those with corneal scar (IL-6: 44.1 ± 15.0, P= .0077; IL-17A: 4.1 ± 0.7, P= .034; E-selectin: 2439 ± 302, P= .039; and P-selectin: 5673 ± 1553, P= .017). Multiple AqH cytokine levels were elevated in chronic ocular surface diseases.

The Conjunctiva-Associated Lymphoid Tissue in Chronic Ocular Surface Diseases.

Ocular surface diseases (OSDs) represent a widely investigated field of research given their growing incidence and the negative impact on quality of life. During OSDs, cytokines generated by damaged epithelia trigger and deregulate the lymphoid cells composing the eye-associated lymphoid tissues, inducing an immune-mediated chronic inflammation that amplifies and propagates the disease during time. The conjunctiva-associated lymphoid tissue (CALT), given its particular position that permits immune cells covering the cornea, might play a crucial role in the development of OSDs. Despite the recognized inflammatory role of mucosa-associated lymphoid tissues in other stations taking contact with the external environment (gut or bronchus), CALT did not gain the deserved consideration. In the last years, the diffusion of the in vivo confocal microscopy (IVCM) stimulated the interest to CALT, especially in dry eye, ocular allergy, and glaucoma. Though the initial stimuli were different, IVCM documented similar changes, represented by increased lymphoid cells within the diffuse layer, follicles and interfollicular spaces. These findings, which need to be validated by immunohistology, support the CALT stimulation during OSDs. However, while an involvement of the CALT in OSDs is hypothesizable, the exact role of this structure in their pathogenesis remains unclear and warrants further investigations.

Thymosin Beta 4: A Potential Novel Therapy for Neurotrophic Keratopathy, Dry Eye, and Ocular Surface Diseases.

Chronic ocular surface diseases such as dry eye, blepharitis, and neurotrophic keratopathies represent a significant and a growing therapeutic challenge. The basis of this expanding prevalence is multifactorial and may due to issues such as an aging population, an increasing use of video display terminals, and increases in frequency of refractive surgeries. The growing incidence of diseases such as diabetes may also be a contributing factor. Current treatments for ocular surface disease include artificial tears, lubricants, tear duct plugs, steroids, antibiotics, cyclosporine, scleral lenses, and serum tears. Treatment choices depend on the type and severity of the disease, but in general positive outcomes are limited because many of these treatments do not fully address the underlying disease process or promote mechanisms that facilitate long-term wound repair. From minor corneal injuries to more severe inflammatory-mediated pathologies, clinicians need agents that promote corneal healing and reduce the inflammatory response to prevent visual disturbances and improve quality of life. A focus on treatments that reduce the inflammatory responses while accelerating corneal epithelial growth would represent a major step forward from current treatment options. Increasing evidence suggests that thymosin beta 4 (Tβ4), a naturally occurring polypeptide, can elicit this spectrum of therapeutic responses: a rapid corneal reepithelialization and a reduction in corneal inflammation. This chapter serves as a review of standard therapies as well as recent advancements in the development of newer therapies that includes the use of Tβ4 that is proving to be an exciting new agent for the management of ocular surface disease.

Escherichia coli Nissle 1917 bacterial ghosts retain crucial surface properties and express chlamydial antigen: an imaging study of a delivery system for the ocular surface.

To target chronic inflammatory ocular surface diseases, a drug delivery platform is needed that is safe, possesses immunomodulatory properties, and can be used either for drug delivery, or as a foreign antigen carrier. A new therapeutic approach that we have previously proposed uses nonliving bacterial ghosts (BGs) as a carrier-delivery system which can be engineered to carry foreign antigens and/or be loaded with therapeutic drugs. The parent strain chosen for development of our BG delivery system is the probiotic Escherichia coli strain Nissle 1917 (EcN), whose intrinsic properties trigger the innate immune system with the flagella and fimbriae used to attach and stimulate epithelial cells. In previous studies, we have shown that EcN BGs are safe for the ocular surface route, but evidence that EcN BGs retain flagella and fimbriae after transformation, has never been visually confirmed. In this study, we used different visualization techniques to determine whether flagella and fimbriae are retained on EcN BGs engineered either for drug delivery or as a foreign antigen carrier. We have also shown by immunoelectron microscopy that EcN retains two foreign antigens after processing to become EcN BGs. Furthermore, we demonstrated that BGs derived from EcN and expressing a foreign antigen attachment to conjunctival epithelial cells in vitro without causing reduced cell viability. These results are an important step in constructing a delivery system based on a nonliving probiotic that is suitable for use in ocular surface diseases pairing immunomodulation and targeted delivery.

Prosthetic Replacement of the Ocular Surface Ecosystem as Treatment for Ocular Surface Disease in Patients with a History of Stevens–Johnson Syndrome/Toxic Epidermal Necrolysis

To report the visual outcomes of prosthetic replacement of the ocular surface ecosystem (PROSE) treatment in patients with ocular surface disease related to Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN). Retrospective cohort study. We included 86 patients (167 eyes) with history of SJS/TEN who underwent PROSE treatment from January 1, 2006, to January 1, 2011. Etiology, previous interventions, change in visual acuity, change in visual function, and duration of follow-up are reported. Paired t test and Friedman test with Dunn's post hoc test for multiple comparisons were used for statistical analysis. Visual acuity at last follow-up and visual function based on the National Eye Institute 25-item Visual Functioning Questionnaire (NEI VFQ-25) at 6 months. We treated 35 males and 51 females with a history of SJS/TENS; median age was 36 years. The most common reported etiologies for SJS/TENS were antibiotics (n= 25), ibuprofen (n= 15), and lamotrigine (n=11). The median visual acuity at the initial visit was 20/60 (range, 20/400-20/25; 0.48 logarithm of the minimum angle of resolution [logMAR]), and the visual acuity at completion of customization was 20/25 (range, 20/200-20/20; 0.096 logMAR; P < 0.001), with no decline in median acuity at the end of follow-up. Median duration of follow-up was 16 months. There was a significant improvement in the visual function of the patients based on the NEI VFQ-25 questionnaire (mean of 48 points at baseline vs. mean of 72 points at 6 months; P<0.001). In addition, there was also an improvement in the self-reported general health of the patients (mean of 57 points at baseline vs. mean of 65 points at 6 months; P < 0.01). In a large cohort of patients with chronic ocular surface disease related to SJS/TEN, PROSEtreatment offers sustained and significant large improvement in visual function and acuity.

Episodes of Microbial Keratitis With Therapeutic Silicone Hydrogel Bandage Soft Contact Lenses

To report the therapeutic practice patterns of silicone hydrogel (SiH) bandage soft contact lenses (BSCL) and the resultant rate of microbial keratitis (MK). A retrospective case series of patients treated with therapeutic BSCLs for ocular surface disease from January 2006 to January 2009 in a tertiary care cornea practice. All patients had a history of ocular surface disease. Seventy-four patients were treated with a therapeutic SiH BSCL (102 intervals of use) for complicated ocular surface disease. Two patients developed infectious corneal infiltrates (2/102, 2.0%) [corrected]. Two of 3 MK episodes were in patients with limbal stem-cell deficiency (2/102, 2.0%). Therapeutic SiH BSCLs were safely used in most patients. However, results suggest that prophylactic antibiotic use did not eliminate the risk for MK with SiH BSCL use in patients with chronic ocular surface disease.

Effect of autologous platelet-rich plasma on persistent corneal epithelial defect after infectious keratitis

Platelet-rich plasma (PRP) harbors high concentrations of growth factors related to the promotion of wound healing. We evaluated the efficacy of PRP eyedrops in the treatment of persistent epithelial defects (PEDs). Autologous PRP and autologous serum (AS) were prepared from whole blood. The concentrations of transforming growth factor (TGF)-β1, TGF-β2, epidermal growth factor (EGF), vitamin A and fibronectin in the PRP and AS were analyzed and compared. The corneal epithelial healing efficacy of PRP was compared with that of AS in patients with PED induced by post-infectious inflammation. The concentrations of TGF-β1, TGF-β2, EGF, vitamin A and fibronectin in the PRP and AS were not statistically different. However, the concentrations of EGF in the PRP were significantly greater than in the AS. AS was used in 17 and PRP in 11 eyes of 28 patients. The healing rates of the corneal epithelia of the PRP-treated eyes were significantly higher than those treated with AS. The PRP was effective in the treatment of PEDs. This may be attributable to its high concentration of platelet-contained growth factors, most notably EGF. PRP could be an effective, novel treatment option for chronic ocular surface disease.

A Case of Bilateral Silent Sinus Syndrome Presenting With Chronic Ocular Surface Disease

The silent sinus syndrome is characterized by atelectasis of the maxillary sinus in the setting of subclinical maxillary sinusitis and obstruction of the osteomeatal unit. The resultant expansion of orbital volume causes enophthalmos and hypoglobus. A review of the literature reveals only unilateral cases. The authors present a case of bilateral silent sinus syndrome presenting with chronic ocular surface disease. A 56-year-old man was referred for tarsorrhaphy to treat a chronic recurrent corneal ulcer. Exam revealed an area of corneal thinning in the left eye. The patient appeared cachectic and there was enophthalmos, hypoglobus, and lagophthalmos on both sides, left worse than right. Due to the patient's appearance and a history of sinonasal malignancy, recurrent malignancy was suspected. A systemic workup was unrevealing, and radiographic studies showed the features of silent sinus syndrome bilaterally. The patient underwent sinus surgery and placement of a left orbital floor implant.

Re: “A Case of Bilateral Silent Sinus Syndrome Presenting With Chronic Ocular Surface Disease”

Ophthalmic Plastic & Reconstructive Surgery: September 2011 - Volume 27 - Issue 5 - p 393 doi: 10.1097/IOP.0b013e318227160f

Reply re: “A Case of Bilateral Silent Sinus Syndrome Presenting With Chronic Ocular Surface Disease”

Reply re: “A Case of Bilateral Silent Sinus Syndrome Presenting With Chronic Ocular Surface Disease”

The Clinical Experience of Acanthamoeba Keratitis at a Tertiary Care Eye Hospital

In recent years, outbreaks of Acanthamoeba keratitis (AK) have been reported worldwide. The purpose of this study was to examine the clinical experience of AK at the Massachusetts Eye and Ear Infirmary. A retrospective case review was completed on patients with infectious keratitis whose corneal cultures were positive for Acanthamoeba between January 2000 and December 2008. The clinical characteristics and visual outcomes were examined in those patients with a follow-up period greater than 6 months. Four cases were identified between January 2000 and December 2003, whereas 26 cases were identified between January 2004 and December 2008. Charts before 2004 were unavailable for review. A total of 15 cases between 2004 and 2008 had a follow-up period of greater than 6 months. In these cases, possible risk factors associated with AK included soft contact lens wear (12 of 15 cases), exposure to freshwater or saltwater sources (8 of 15 cases), chronic ocular surface disease (6 of 15 cases), ocular trauma (3 of 15 cases), and concomitant infectious keratitis (2 of 15 cases). Four cases were associated with the use of Advanced Medical Optics Complete MoisturePlus Multi-Purpose Solution. Many cases were recalcitrant to medical therapy alone, necessitating therapeutic penetrating keratoplasty in 8 of 15 cases. The number of AK cases at the Massachusetts Eye and Ear Infirmary has increased since 2004. Contact lens wear and exposure to contaminated water sources were potential risk factors for AK. Clinicians should maintain a high clinical suspicion for AK in cases of atypical keratitis with known risk factors for AK.

Preservative-Free Low-Dose Dexamethasone for the Treatment of Chronic Ocular Surface Disease Refractory to Standard Therapy

To evaluate the short-term safety and efficacy of topical preservative-free dexamethasone 0.01% for the treatment of ocular surface disease and/or tearing refractory to conventional treatments. Retrospective chart review of all patients who received topical unpreserved dexamethasone 0.01% (Leiters Pharmacy, San Jose, CA). Follow-up visits were reviewed for subjective responses to the formulation and intraocular pressure. Responses were graded as significant/complete resolution of symptoms (50%-100% improvement), mild (25%-50% improvement), or no improvement. Thirty-one patients received topical unpreserved dexamethasone 0.01% for the treatment of ocular surface disease. Follow up ranged from 4 to 60 months (average, 11.5 weeks). Twenty patients (65%) reported moderate or complete resolution of ocular symptoms. Seven patients (22%) had mild improvement in their symptoms. Four patients (13%) had no change in ocular symptoms. No patient in our series developed an elevation of intraocular pressure greater than 5 mm Hg above baseline intraocular pressure. No patient developed intraocular pressure greater than 22 mm Hg. Topical nonpreserved 0.01% dexamethasone could be an effective therapy for recalcitrant chronic ocular surface disease.

Dry Eye Disease as an Inflammatory Disorder

Purpose: Dry eye disease (DED) is a prevalent inflammatory disorder of the lacrimal functional unit of multifactorial origin leading to chronic ocular surface disease, impaired quality of vision, and a wide range of complications, eventually causing a reduction in quality of life. It still is a frustrating disease because of the present scarcity of therapies that can reverse, or at least stop, its progression.Methods: A comprehensive literature survey of English-written scientific publications on the role of inflammation in DED.Results: New investigations have demonstrated that a chronic inflammatory response plays a key role in the pathogenesis of human DED. Additionally, correlations between inflammatory molecules and clinical data suggest that inflammation can be responsible for some of the clinical symptoms and signs.Conclusions: Research efforts to clarify its pathophysiology are leading to a better understanding of DED, demonstrating that inflammation, in addition to many other factors, plays a relevant role.

The relationship between preoperative clinical scores and immunohistological evaluation of surgically resected tissues in chronic severe ocular surface diseases

To clarify the relationship between clinical symptoms and histological status in patients with ocular cicatricial pemphigoid (OCP) and Stevens-Johnson syndrome (SJS). Clinical symptoms of four OCP and eight SJS patients in the chronic phase were scored with our recently proposed grading system. The histological status of the pannus tissue removed from the corneal surface during surgery was investigated using immunohistological techniques. All participants showed total loss of the palisades of Vogt and conjunctivalization of the entire corneal surface. All pannus tissues expressed the conjunctival epithelium marker CK4/13. The pannus tissue in clinically keratinized SJS expressed skin epidermal major cytokeratins, but the tissues of nonkeratinized SJS did not. Clinical observation and the use of our recently proposed grading system agreed with the immunohistological status with respect to keratinization, cell proliferation, and corneal/conjunctival cell typing. These findings facilitate our understanding of the pathogenesis of OCP and SJS, and will hopefully contribute to the development of future treatment strategies and improve predictions of the postoperative prognosis of ocular surface reconstruction in patients with OCP and SJS.

Clinical Effects of Combination Therapy Using Heparin and Phospholipid in Severe Dry Eye Syndrome

Purpose: To evaluate the therapeutic effects of topical heparin (Hylo-Parin, Ursapharm Saarbr cken, Germany) and spray type phospholipids (Tears Again, Optima Pharmazeutische GmbH. Freising, Germany) in severe dry eye syndrome resistant to conventional therapy. Methods: Twenty eyes of ten patients with refractory severe dry eye were treated with Hylo-Parin (two times a day) and Tears Again (three times a day) for three months. Before and one and three months after treatment, a symptom questionnaire was administered to the patients. The ocular surface disease index (OSDI), tear film break-up time, Schirmer test, conjunctival fluorescein staining examinations and filamentary keratitis were evaluated. Results: After using Tears Again and Hylo-Parin, the OSDI score improved from 64.13 15.12 to 43.80 15.87 (p 0.65 to 2.3 0.73 seconds (p 0.75 to 3.25 0.97 (p and Hylo-Parin are considered as new treatment modalities for severe dry eye syndrome and filamentary keratitis in patients with chronic ocular surface disease resistant to conventional therapy. These treatments require additional research.

Sjögren’s Syndrome-Like Ocular Surface Disease in Thrombospondin-1 Deficient Mice

Thrombospondin-1 (TSP-1) is a major activator of latent transforming growth factor-beta in vitro as well as in vivo. Mice deficient in TSP-1, despite appearing normal at birth, develop a chronic form of ocular surface disease that is marked by increased apoptosis and deterioration in the lacrimal gland, associated dysfunction, and development of inflammatory infiltrates that result in abnormal tears. The increase in CD4(+) T cells in the inflammatory infiltrates of the lacrimal gland, and the presence of anti-Sjögren's syndrome antigen A and anti-Sjögren's syndrome antigen B antibodies in the serum resemble autoimmune Sjögren's syndrome. These mice develop an ocular surface disorder dry eye that includes disruption of the corneal epithelial layer, corneal edema, and a significant decline in conjuctival goblet cells. Externally, several mice develop dry crusty eyes that eventually close. The inflammatory CD4(+) T cells detected in the lacrimal gland, as well as those in the periphery of older TSP-1 null mice, secrete interleukin-17A, a cytokine associated with chronic inflammatory diseases. Antigen-presenting cells, derived from TSP-1 null, but not from wild-type mice, activate T cells to promote the Th17 response. Together, these results indicate that TSP-1 deficiency results in a spontaneous form of chronic dry eye and aberrant histopathology associated with Sjögren's syndrome.

0.05% cyclosporine a for treatment of chronic severe ocular surface disease

To evaluate the effects of topical cyclosporin A on severe and corticodependent chronic ocular surface disorders (OSD), in immune inflammatory disease. Experimental study, Centre hospitalier universitaire (CHU) Bretonneau, Tours, France. Twenty-one patients diagnosed with dry eye syndrome secondary to vernal keratoconjunctivitis (7 cases), atopic keratoconjunctivitis (8 cases), and ocular rosacea (6 cases) were treated twice a day with a 0.05% cyclosporin ophthalmic emulsion. Corneal and conjunctival staining, Oxford score, and symptoms severity assessment (OSDI score) were conducted from the beginning of the cyclosporin treatment up to the end of study. Other collected data included visual acuity, intraocular pressure measurements, an adverse effects questionnaire, and evaluation of the use of adjunctive corticosteroids therapy. Topical cyclosporin 0.05% gave significant long-term improvement of visual acuity (p = 0.018), symptoms severity (OSDI score, p = 0.001), corneal and conjunctival staining (van Bijesterveld score, p = 0.0003), and Oxford score (p = 0.0002). Topical cyclosporin allowed for less corticosteroid treatment in all cases (p = 0.04), and broke it off with no long-term recurrence in 15 cases (71%). No severe adverse effect occurred, but 3 patients (14%) stopped cyclosporin treatment because of increasing ocular symptoms. Given our results, topical cyclosporin represents a new well-tolerated treatment for severe and corticodependent chronic ocular surface disorders. In monotherapy or in association with a corticotherapy, topical cyclosporin could be efficient in any OSD involving immune-based inflammation.