Ocular hypertensive and anti-inflammatory responses to different dosages of topical dexamethasone in children: a randomized trial.

BACKGROUND: The purpose of the present study was to investigate the ocular hypertensive and anti-inflammatory responses to two different dosage schedules of 0.1% topical dexamethasone in a population of Chinese children undergoing strabismus surgery. METHODS: Children undergoing bilateral strabismus surgeries were randomly assigned to receive topical 0.1% dexamethasone eye drops four times daily (group A) or twice daily (group B) for 4 weeks. Intraocular pressure (IOP) and anti-inflammatory responses were monitored for 8 weeks. RESULTS: A total of 137 children with mean age 6.5 years (SD, 1.9 years; range, 3-10 years) participated in the study. The IOP increased significantly after 4 weeks in both groups compared to the preoperative values (P < 0.001). Peak IOP ranged from 14.0 to 50.3 mmHg in group A and 11.0-41.3 mmHg in group B. Cases in group A (mean, 13.8 mmHg; SD, 8.4 mmHg) had a greater net increase in IOP than cases in group B (mean, 10.2 mmHg; SD, 6.2 mmHg; P = 0.004). Younger-aged children had higher peak IOP (r = -0.244, P = 0.048), and attained the peak IOP earlier (r = 0.252, P = 0.041) in group A. There was no significant difference in ocular inflammatory response between the two groups. CONCLUSION: Ocular hypertensive effect to topical 0.1% dexamethasone is dose and age dependent in children. Twice-daily 0.1% topical dexamethasone eye drops control inflammation after strabismus surgery as effectively as four-times-daily dosage, but induces less increase in IOP, and may be a better treatment schedule.

Comparative study on the safety and efficacy of different cycloplegic agents in children with darkly pigmented irides.

BACKGROUND: The ideal cycloplegic drug that is safe, effective and convenient in children is not yet available. This study aimed to evaluate the safety and efficacy of three cycloplegic regimens in hyperopic children with pigmented irides. The responses to cycloplegia in different age groups and presence of strabismus were also compared. METHODS: Tropicamide 0.5% and phenylephrine 0.5% (regimen I), tropicamide 1.0% and cyclopentolate 1.0% (regimen II), and atropine 1.0% (regimen III) were evaluated in 25 children using a crossover study design. Cycloplegic refractions were assessed. RESULTS: The mean age of the children was 5.7 +/- 2.0 years (range 2.5-10.8 years). Six (24.0%) of them had strabismus. The spherical equivalent (SE) refraction for regimens I, II and III were +5.11 +/- 2.04 D, +5.29 +/- 1.89 D and +5.71 +/- 1.90 D, respectively, and were significant different from the manifest SE (+3.95 +/- 2.17 D) (P < 0.001). There was no statistical difference between regimen I and II in children without strabismus (P = 0.258) or aged older than 5 years (P > 0.050). CONCLUSION: In older children, regimen I was as effective as regimen II and can be used to avoid cyclopentolate toxicity.

Intraocular pressure profile of a child on a systemic corticosteroid.

PURPOSE: To report the ocular hypertensive response to high-dose systemic corticosteroid in a pediatric patient. DESIGN: Observational case report. METHODS: A 9-year-old patient with leukemia received oral prednisolone at a dosage of 2.3 mg/kg/d for 5 weeks, followed by a 4-month break and then a 4-week course of oral dexamethasone at 10 mg/d. Detailed ocular examination was performed for both eyes before and regularly throughout the two courses of treatment. RESULTS: The intraocular pressure in both eyes rose to almost 40 mm Hg after only 8 days of oral corticosteroid. On stopping systemic corticosteroid, the intraocular pressure rapidly returned to baseline level within 2 days. A similar intraocular pressure profile was recorded for both eyes during the course of oral dexamethasone. The patient remained largely asymptomatic throughout. CONCLUSIONS: Systemic corticosteroid may give rise to significant but asymptomatic ocular hypertension in pediatric patients.

Ocular-hypertensive and anti-inflammatory response to rimexolone therapy in children.

OBJECTIVE: To compare the ocular-hypertensive and anti-inflammatory response to rimexolone (116-hydroxy-16alphafluoro-6alphamethylpresdnisolone) and fluorometholone (21-deoxy-9alphafluoro-6alphamethylprednisolone) therapy in children's eyes. METHODS: With parental consent, children who underwent surgical procedures for bilateral symmetric strabismus from January 18, 2000, through November 16, 2001, were recruited. One eye was randomized to receive topical 1% rimexolone while the contralateral eye received topical 0.1% fluorometholone, 4 times daily for 4 weeks. MAIN OUTCOME MEASURES: Intraocular pressures and anti-inflammatory responses were the main outcome measures and were serially measured postoperatively for 8 weeks. RESULTS: Fifty-four children, aged from 4 to 8 years (mean [SD] age, 5.33 [1.26] years), participated in the study. Intraocular pressure increased significantly in both treatment groups compared with the preoperative values (P<.001). The mean (SD) peak intraocular pressure was significantly higher in the rimexolone-treated group, 19.7 (6.1) vs 17.6 (4.6) mm Hg (P<.001). Similarly, the mean (SD) net increase in intraocular pressure (P<.001), was also higher in the rimexolone-treated eyes, 5.9 (4.4) vs 3.9 (4.1) mm Hg (P<.001). In addition, a greater percentage of the rimexolone-treated patients had no conjunctival erythema on days 13 (11.1% vs 0.0%) and 20 (88.9% vs 55.6%) (P =.03). CONCLUSIONS: Rimexolone seems to be a more effective anti-inflammatory agent than fluorometholone. However, unlike adults, the ocular-hypertensive effect in children treated with rimexolone was higher. It would be desirable to monitor the intraocular pressure regularly when rimexolone therapy is used in children.

Loss of heterozygosity and mutations are the major mechanisms of RB1 gene inactivation in Chinese with sporadic retinoblastoma.

We investigated sequence alternation, promoter methylation, and loss of heterozygosity (LOH) of the RB1 gene as possible mechanisms of its inactivation in retinoblastoma. In 42 Chinese patients with sporadic retinoblastoma, the promoter and entire coding region of RB1 were examined for sequence changes. Status of methylation of the CpG-rich island at the 5'end was determined by methylation specific PCR assay. We detected 15 RB1 mutations in 38% (16/42) of the retinoblastoma patients, among them 19% (8/42) were germ-line mutations. A total of nine novel mutations were identified: E54X, S114X, I126S, g73779insG, D718N, IVS2+1G>C, IVS14+1G>C, IVS21+1G>C, and a complex alteration g78177G>T/g78176insTT leading to 543X. Most of them are likely to affect the RB1large pocket domain through the production of truncated gene products. None of the DNA samples showed methylation at the RB1promoter. In 15 cases where both normal and cancerous retinoblastoma tissue specimens were available, allelic loss according to microsatellite markers within or distal to the RB1 locus was analyzed and immunohistological staining for RB1 expression performed. Among them, frequency of LOH at 13q14 was found to be high at 60% (9/15) with no segregation with unilateral tumors. All these nine tumors did not express RB1 protein, showing an association of LOH at the RB1 locus with its loss of expression in retinoblastoma. Our results indicate that the RB1 gene in sporadic retinoblastoma is commonly inactivated because of loss-of-function mutations and loss of heterozygosity but not by the epigenetic phenomenon of promoter hypermethylation.

Impaired expression and promotor hypermethylation of O6-methylguanine-DNA methyltransferase in retinoblastoma tissues.

PURPOSE: To investigate the role of epigenetic changes in the promoter region of tumor-suppressor genes in the retinoblastoma genome and to study the disruption of expression of O6-methylguanine-DNA Methyltransferase (MGMT) due to aberrant methylation and its association with retinoblastoma. METHODS: A series of 23 retinoblastoma tissue specimens and 2 retinoblastoma cell lines (Y79 and WERI-Rb1) were subjected to methylation-specific PCR (MSP) analysis of hypermethylated genes identified in human cancers, including p14(ARF), p15(INK4b), p16(INK4a), VHL, and MGMT. Further, the expression of MGMT was studied by immunohistochemistry and, when fresh tissue was available, by Western blot analysis and RT-PCR. RESULTS: Aberrant methylation of at least one MGMT locus was detected in 8 of the 23 tumors (35%), all of which (100%) had impaired or absent expression of MGMT. The remaining 15 tumor specimens were nonmethylated, and, among them, 7 (43%) showed defective expression. No methylation of tumor DNA was found on the p14(ARF), p15(INK4b), p16(INK4a), and VHL genes. Hypermethylation in the MGMT promoter was found to be prominently present in retinoblastoma with poor tissue differentiation, and was more frequently detected among patients with bilateral disease. Production of MGMT was consistent with expression of mRNA. No methylation of MGMT promoter was detected in the two retinoblastoma cell lines (Y79, WERI-Rb1). CONCLUSIONS: The data show a clear association between impaired production of MGMT and hypermethylation of the MGMT promoter, which appeared to relate to early onset and poor differentiation, suggesting that epigenetic silencing of MGMT by methylation of the promoter and reduced expression of MGMT may play an important role in the development and progression of retinoblastoma.

Bilateral congenital corneal keloids and anterior segment mesenchymal dysgenesis in a case of Rubinstein-Taybi syndrome.

PURPOSE: To report the unusual association of bilateral corneal keloids and anterior segment mesenchymal dysgenesis in a child with Rubinstein-Taybi syndrome. METHODS: Case report of a 2-year-old boy. RESULTS: Excision of the epicorneal mass in the right eye was followed by recurrence of the lesion. Multiple penetrating keratoplasties were unsuccessful in reconstructing the anterior segment because of recurrent corneal epithelial breakdown, suggesting limbal stem cell insufficiency. Histopathology and electron microscopy of the excised mass lesion showed features typical of a corneal keloid: thickened keratinized epithelium, absent Bowman's layer, and fibrovascular hyperplasia, with haphazard orientation of the collagen lamellae. Ultrasound biomicroscopy and intraoperative findings suggested a diagnosis of Peter anomaly, but genetic analysis did not show a PAX6 mutation. CONCLUSION: The findings in our patient add to the spectrum of ocular changes described in Rubinstein-Taybi syndrome and confirm earlier reports of poor ocular prognosis in corneal keloids and Rubinstein-Taybi syndrome.