Cyclosporine A 1% Eye drops for the Treatment of Subepithelial Infiltrates After Adenoviral Keratoconjunctivitis
Cole Eye Institute, Cleveland Clinic, Cleveland, OH, USA. Cornea
(Impact Factor: 2.04).
06/2011; 30(9):958-61. DOI: 10.1097/ICO.0b013e31820cd607
To describe the use of cyclosporine A (CSA) 1% eye drops for the treatment of symptomatic corneal subepithelial infiltrates (SEI) occurring as a sequelae of adenoviral keratoconjunctivitis (AK) that are resistant to tapering of corticosteroid eye drops.
This is a retrospective case series of patients seen at 2 institutions who had symptomatic corneal SEI occurring after AK that was resistant to tapering of corticosteroid eye drops and who were subsequently treated with CSA 1%. Information gathered included basic demographic information (age and sex), involved eye(s), duration of symptoms, initial best spectacle-corrected visual acuity (BSCVA), type of corticosteroid used, clinical course, and best spectacle-corrected visual acuity at the last follow-up visit.
Twelve eyes of 7 patients had symptomatic SEI develop after AK that were responsive to corticosteroid eye drops but were resistant to tapering. After the initiation of CSA eye drops, the corticosteroid eye drops could be tapered, and all eyes could be maintained on CSA eye drops once per day or less. Mean follow-up time was 13.0 months (range, 4-28 months).
CSA eye drops may be an effective corticosteroid-sparing agent for the treatment of SEI after AK. The use of CSA in this setting warrants further study.
Available from: Philippe Daull
- "Systemic CsA has been used in organ transplantation for the past few decades, and topical CsA has been used for the treatment of ocular surface diseases since the early 1980s with considerable success. Systemic and topical hospital CsA preparations were used to treat severe ocular surface diseases including uveitis, cornea transplant rejection, severe vernal keratoconjunctivitis (VKC), necrotizing scleritis, Behçet syndrome, high-risk corneal transplantation, and adenoviral kerato-conjunctivitis [2-6]. In 2003, an ophthalmic anionic emulsion containing 0.05% CsA (Restasis®, Allergan, Irvine, CA, USA) was approved by the United States Food and Drug Administration (FDA) to increase tear production in patients whose tear production is presumed to be suppressed due to ocular inflammation associated with keratoconjunctivitis sicca (dry eye syndrome) [7,8]. "
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ABSTRACT: Topical preparations of cyclosporine (CsA) are common therapeutics for the treatment of dry eye. However, they are not devoid of side effects, such as allergy and irritation. The present study aimed at evaluating the safety profile of a new CsA formulation in cationic emulsion (CEm) in vitro with a dynamic corneal wound healing assay using human corneal epithelial (HCE) cells, and in vivo in a rabbit acute toxicity model.
Three different csa formulations were tested: 1) 0.05%CsA-CEm, 2) commercial 0.05%CsA-Anionic emulsion (CsA-AEm, Restasis®), and 3) 0.05%CsA-Oil solution. Phosphate buffered saline (PBS) was used as negative control and 0.02% benzalkonium chloride (BAK) as the toxic control. In vitro, a wound was created by scratching through a confluent HCE cell layer and exposed 30 min to 1/10 dilutions of the different formulations. Cytotoxicity, cell migration, and proliferation were performed to analyze the recovery at days 1, 2, and 3. In vivo, the eye drops were applied to rabbit eyes 15 times at 5-min intervals. The ocular surface structures were examined with a slit-lamp and by corneal in vivo confocal microscopy (IVCM) for detailed examination of corneal epithelium, stroma, limbus, and conjunctiva-associated lymphoid tissue (CALT) structures.
The in vitro study confirmed that a 0.02% BAK solution delayed the corneal healing process (-57%) by severely damaging the remaining HCE cells. The other formulations maintained a normal healing rate with a similar behavior for CsA-CEm, CsA-AEm, and PBS with no significant differences (at D3, 66%-74% closure). In the rabbit, 0.02%BAK showed the highest toxicity, inducing redness, chemosis with damaged corneal epithelium, and inflammatory cell infiltrations. CsA-AEm and CsA-Oil induced moderate infiltrations of inflammatory cells around the CALT. CsA-CEm presented the lowest toxicity with patterns similar to PBS.
The combination of these in vitro and in vivo models evaluated the tolerance/cytotoxicity and the dynamic wound healing potential of CsA in different formulations. While CsA-AEm, CsA-CEm, and CsA-Oil are generally well tolerated, only CsA-CEm appeared to maintain the HCE cells' normal healing rate in vitro and low levels of inflammation in vivo.
Available from: Yusuf Yildirim
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ABSTRACT: Abstract Purpose: To report the effect of topical Cyclosporine-A (CsA) 0.05% on corneal morphologic and functional parameters in patients with dry eye. Method: In this prospective and observational, 30 eyes of 30 patients who received topical CsA 0.05% for treatment of dry eye were evaluated. Each clinical examination included a routine clinical examination with the Schirmer I test, and tear film break-up time (TBUT) was performed at baseline and after 1, 2, 3, and 6 months of treatment. All participants also underwent central corneal thickness (CCT) measurements with ultrasound pachymetry, endothelial cell density (ECD) with specular microscopy, corneal topographical evaluation with Orbscan II, and corneal biomechanical parameters with Ocular Response Analyzer measurements at baseline and after treatment. Results: The Schirmer I test and TBUT were significantly improved after treatment (for both; P<0.01). The CCT, topographical findings, ECD, and corneal biomechanical parameters were not significantly different at baseline and follow-up visits (P>0.05). No serious adverse effects were seen at follow up visits. Conclusion: The study showed that Topical CsA 0.05% caused no changes on corneal morphologic and functional parameters.
Available from: Erol Coşkun
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To evaluate the treatment with topical 0.05% cyclosporine A (CsA) in patients with subepithelial corneal infiltrates (SEI).
We reviewed 16 patients (22 eyes) before and after the treatment with 0.05% CsA eye drops. All patients had been treated previously with topical corticosteroids without any improvement and also they had to stop the medication secondary to intraocular pressure elevation. The objective data recorded included best-corrected visual acuity (BCVA), evaluation of corneal subepithelial infiltrate scores (CSIS), intraocular pressure (IOP) prior to treatment and the last follow-up visit.
Six males (37.5%) and 10 females (62.5%), mean age of 35.2 ± 16.6 years, were included. The patients’ average topical CsA use duration was 5.1 ± 3.5 months (1 – 13 months). The average follow up time of the patients was 9.2 ± 4.7 months (4 – 22 months). One patient, although he didn’t have a 0 scale of SCIS, did not show up for follow up examinations after six months. The mean BCVA (logarithm of the minimum angle of resolution) before and after the treatment were 0.15 ± 0.15 and 0.07 ± 0.07 respectively, CSIS 1.68 ± 0.89 and 0.23 ± 0.53 respectively, IOP 18.50 ± 3.82 and 16.86 ± 2.76 mmHg respectively. There were statistically significant improvements in BCVA (p = 0.002), reduction of CSIS (p = 0.002) and reduction of IOP (p < 0.001) prior to treatment and the last follow-up visit. 18 eyes (81.9%) showed clinical improvement and 4 (18.1%) had decreased SEI which did not fully disappear during the treatment period. The eyes which reached CSIS score 0 (18 eyes) were treated with CsA for 1 – 13 months; while the eyes which had clinical improvement but had not CSIS score 0 (4 eyes) were decided to discontinue of CsA treatment in last follow-up visit. There were recurrences in 2 eyes 3 months after the treatment. Patients reported reduction in the severity of symptoms after the treatment. Most of the patients reported no foreign body sensation, glare, or other side effects with topical CsA treatment. Overall, patients noted an improvement in vision and satisfaction with topical 0.05% CsA treatment.
Topical 0.05% CsA is a safe and effective alternative treatment in patients with SEI who do not respond to other treatment modalities or have undesired side effects from topical steroids.
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