Loteprednol Etabonate in Ocular Inflammation undergone cataract surgery with IOL implantation.42 The results of
both studies showed significant treatment effects on pain, photobia, tearing, and pain. Pooled results showed that the proportions of at-risk subjects with resolution of pain or discomfort were significantly greater in the groups who received loteprednol than in those who received vehicle alone.
Combination Therapy with Non-steroidal Anti-inflammatory Drugs
NSAIDs are an important component of the post-operative management of refractive and cataract surgery due to their analgesic and anti-inflammatory effects. LE and other topical steroids act synergistically in combination with NSAIDs, since their mechanism of action differs from that of NSAIDs. NSAIDs primarily act on the cyclooxygenase (COX-1 and COX-2) pathway, minimizing prostaglandin formation, whereas steroids primarily act on phospholipase A2, inhibiting the release of arachidonic acid. In general, cataract surgeons use a combination of anti-inflammatory agents as part of their post-operative regimens and a combination of steroids and NSAIDs has been found to be more effective than steroids alone.40
A prospective trial
found that combination therapy of prednisolone and ketorolac is more beneficial than monotherapy with either agent in the prevention of CME.43
Although no published studies echo this synergy between NSAIDs and LE, it stands to reason that such synergies are expected and many surgeons combine these two agents following routine or complicated cataract surgery.
Long-term Use of Loteprednol Etabonate and the Impact on Intraocular Pressure The impact of LE on IOP is minimal compared to other topical corticosteroids. Long-term use of LE results in clinically significant (10mmHg or greater) elevations of IOP in only a small fraction of cases. A study evaluating all patients participating in LE studies found that only 1.7% of those receiving LE for 28 days or longer had clinically significant elevations of IOP compared with 6.7% of those taking PA. In patients not wearing contact lenses or those taking LE 0.2%, the incidence was reduced to 0.6 and 0.8%, respectively, which was remarkably similar to placebo (see Figure 2).25
In another study, over a 43-day
period, statistically and clinically significant IOP elevations were observed in known steroid responders treated with PA, whereas the IOP changes observed in those taking LE 0.5% were neither clinically nor statistically significant.17
These data are consistent with observations in
clinical practice. A retrospective review of 397 seasonal and perennial allergic conjunctivitis patients who had been prescribed LE 0.2% at least once a day for one to four years recorded no steroid-induced adverse effects. No patient developed increased IOP greater than 4mmHg above baseline.44
As with the use of any steroid, careful patient selection and monitoring is important. Glaucoma patients almost always experience rises in IOP following the application of topical steroids, so monitoring over a few weeks is essential. If an increase is observed, the steroid should be tapered or stopped if possible. If continued steroid therapy is necessary, an ocular hypotensive medication should be given in conjunction with the steroid to reduce the IOP, for example a beta-blocker or alpha-2 agonist such as brimonidine. Selective laser
US OPHTHALMIC REVIEW 6 4 2 0
Figure 2: Incidence of Significant Elevations in Intraocular Pressure (10mmHg or More) in Patients Treated with Loteprednol Etabonate versus Prednisolone Acetate
10 8
All subjects LE Placebo LE = loteprednol etabonate. Source: Novack et al., 1998.25
trabeculoplasty (SLT) is also a useful adjunct to topical steroids in patients with mild IOP elevations.
Long-term Safety of Loteprednol Etabonate Numerous studies have found that LE is well tolerated with no serious treatment-related adverse events44
(see Table 1). After six weeks
of treatment with 0.5% LE, no evidence of systemic absorption of LE or its metabolite PF-71 was observed, nor was there any evidence of adrenal suppression.45
Furthermore, although corticosteroids are
associated with cataracts and diminished immune responses, there are no published cases or reports of LE-induced cataracts. The long- term safety of LE makes it an excellent choice for long-term maintenance therapy. LE is contraindicated in patients with ocular infections due to Acanthamoeba, herpes simplex virus, and fungi.
Conclusion
LE has demonstrated efficacy in clinical studies in a variety of ocular inflammatory conditions and a wealth of evidence supports its use as first-line therapy in clinical practice. It combines the efficacy of PA with a favorable reduction in side effects. Its rapid metabolism makes it safe for the treatment of corneal, ocular surface, and intraocular inflammation. Its applications in induction as well as in maintenance therapy—targeting a wide variety of conditions—make it a versatile treatment option. LE is an ideal medication for the patient requiring prolonged or even lifelong anti-inflammatory therapy, including patients with uveitis, corneal transplantation, previous trauma, glaucoma shunts, or chronic ocular surface disease. In addition, LE can play an integral role in the management of patients who have undergone ocular surgery. LE helps to optimize surgical outcomes through the minimization of inflammation- related post-operative complications and the risk for steroid-related side effects. The development of modified corticosteroids has far-reaching implications for the treatment of inflammatory eye disease and merits continued evaluation in clinical trials to further define the clinical utility of LE and other modified corticosteroids. n
61
Without contacts Prednisolone acetate
% of Subjects
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