[Special features of biological drug therapy in children]. / Tulehdussairauksien biologisen lääkehoidon erityispirteet lapsilla.

Several new biological drugs, of which TNFα blockers are being used most extensively, have in recent years been adopted for the treatment of pediatric inflammatory diseases such as juvenile arthritis and associated chronic iritis, and inflammatory bowel diseases. In special situations the children will be prescribed off-label also other drugs affecting cytokines, e.g. IL-1 and IL-6 blockers. Tailoring of the treatment is possible today with the help of drug level measurements and anti-drug antibody determinations. Severe safety hazards associated with biological drug therapy in children are very rare.

Intense pulsed light therapy (IPL) induced iritis following treatment for a medial canthal capillary malformation.

The popularity of intense pulsed light (IPL) therapy continues to increase due to its relative safety, high skin coverage rate and ability to treat both vascular and pigmented lesions. An often-overlooked risk is the potential for IPL-induced ocular damage. The damage sustained can cause significant, persistent morbidity and can occur even with very limited IPL exposure to the eye.

COX-2 inhibitors prolong trauma-induced elevations of iris hyaluronan.

PURPOSE: To investigate whether and how treatment with COX-2 inhibitors influences hyaluronan responses to a standardized trauma, argon laser induced iritis, in rabbits. METHODS: Two different COX-2 inhibitors were used, SC-236 and rofecoxib. The drugs were administered orally, 6 mg/kg/day and 1.5 mg/kg/day respectively. Iris and aqueous humor hyaluronan concentrations were measured with a radiometric assay at different time points after laser irradiation. RESULTS: The hyaluronan concentration in the iris increased 3-4-fold with a peak concentration of 129.1 microg/g wet weight 2 days after laser irradiation. It then decreased to normal values after 1 week. In eyes treated with either of the COX-2 inhibitors, iris hyaluronan concentrations did not decrease as rapidly and were significantly higher at day 4 and 7 when compared to drug untreated eyes. CONCLUSION: Treatment with COX-2 inhibitors prolongs trauma induced elevation of iris content of endogenous hyaluronan. This may be, at least partly, due to an inhibition of interstitial fluid pressure regulation.

Enhanced ocular anti-inflammatory activity of ibuprofen carried by an Eudragit RS100 nanoparticle suspension.

PURPOSE: To investigate the ocular pharmacodynamic profile of a polymer nanoparticle system loaded with sodium ibuprofen (IBU-RS) in comparison to an aqueous solution of ibuprofen lysinate (IBL) in the rabbit eye both being applied topically. METHODS: Ocular inflammation was elicited by topical application of sodium arachidonate. Inflammation was quantified according to a modified Draize test. The protein level and the number of polymorphonuclear leukocytes in the aqueous humor were assessed after 2 h from arachidonate instillation. The ibuprofen concentration in the aqueous humor was evaluated by HPLC assay. The physico-chemical properties of nanoparticles were also evaluated. RESULTS: The IBU-RS nanosuspension formulation significantly reduced the primary signs of ocular inflammation as well as significantly reducing the protein level and the number of polymorphonuclear leukocytes in the aqueous humor compared with the IBL formulation. Furthermore, the aqueous humor drug concentration from the group treated with IBU-RS was significantly higher compared to the IBL-treated group. The IBU-RS nanosuspensions showed very interesting size and surface charge values, adequate for ophthalmic administration. CONCLUSIONS: The pharmacological profile of the topical IBU-RS nanosuspension formulation described in this study indicates that the dispersion of the drug within RS polymer nanoparticles increased its ocular bioavailability and ultimately its pharmacological activity.

Ocular jellyfish stings.

BACKGROUND: Corneal stings from the sea nettle (Chrysaora quinquecirrha) indigenous to the Chesapeake Bay are usually painful but self-limited injuries, with resolution in 24 to 48 hours. METHODS: Five patients who developed unusually severe and prolonged iritis and intraocular pressure elevation after receiving corneal sea nettle stings were followed for 2 to 4 years. RESULTS: Decreased visual acuity, iritis, and increased intraocular pressure (32 to 48 mmHg) were noted in all cases. Iritis responded to topical corticosteroids and resolved within 8 weeks. Elevated intraocular pressure responded to topical beta blockers and oral carbonic anhydrase inhibitors. Mydriasis (4 of 5 cases), decreased accommodation (2 of 5 cases), peripheral anterior synechiae (2 of 5 cases), and iris transillumination defects (3 of 5 cases) also were noted. Mydriasis and decreased accommodation persisted for 5 months in 1 case and for more than 2 years in another. One patient has chronic unilateral glaucoma. Visual acuity returned to normal in all cases. CONCLUSIONS: The precise relationship between sea nettle venom and the observed clinical responses is not known. Corneal jellyfish stings usually produce a brief and self-limited reaction, but they do have the potential for long-term sequelae.

Effects of sodium naproxen eye drops on rabbit ocular inflammation induced by sodium arachidonate.

Sodium naproxen, a reversible competitive inhibitor of cyclooxygenase, is widely used as an anti-inflammatory agent in clinical practice. The purpose of this study was to determine whether eye drops containing 0.5% (w/v) sodium naproxen reduce a number of inflammatory responses produced by sodium arachidonate in the rabbit's eye. Sodium naproxen eye drops successfully reduced the primary signs of ocular inflammation elicited by 0.5% sodium arachidonate on conjunctiva and iris. However, the drug was less effective in reducing conjunctival inflammation induced by 1% sodium arachidonate. Sodium naproxen treatment significantly reduced the levels of prostaglandin E2 (PGE2), polymorphonuclear leukocytes and protein concentration in aqueous humor samples obtained from the eyes of rabbits treated with 0.5% sodium arachidonate whereas aqueous humor levels of leukotriene B4(LTB4) were not found significantly different from control rabbits. Interestingly, PGE2 as well as LTB 4 "de novo" production by corneas and lenses obtained from rabbits sacrificed 2 h after arachidonate and incubation "in vitro" for 20 min were significantly higher in samples taken from controls than in tissues obtained from the eyes treated with sodium naproxen eye drops. Finally, this drug treatment significantly antagonized the rise in intraocular pressure induced by 0.5% sodium arachidonate. Present data suggest that sodium naproxen may be employed topically to prevent ocular inflammatory reactions where the arachidonic acid cascade is activated.

Efficacy of BW759 (9-[[2-hydroxy-1(hydroxymethyl)ethoxy]methyl]guanine) against herpes simplex virus type 1 keratitis in rabbits.

A promising new nucleoside analog, 9-[[2-hydroxy-1-(hydroxymethyl)ethoxy] methyl]-guanine (BW759), which is structurally similar to acyclovir, was tested against acute herpetic keratitis in the rabbit ocular model. Topical 1-0.1% BW759 given 3-5x per day gave beneficial results in that corneal epithelial involvement, conjunctivitis, iritis, and corneal clouding were reduced even when chemotherapy was initiated at 3 days postinoculation. Under the same conditions, topical BW759 therapy gave slightly better results than acyclovir, and both were better than idoxuridine therapy. Mortality rate and colonization of the trigeminal ganglia by HSV-1 were unaffected by BW759 therapy. Duration of virus, shed into the tear film was reduced by BW759.