Difluprednate versus prednisolone acetate for inflammation following cataract surgery in pediatric patients: a randomized safety and efficacy study.

PurposeTo evaluate safety and efficacy of difluprednate 0.05% ophthalmic emulsion for treatment of postoperative inflammation after cataract surgery in pediatric patients.MethodsThis was a phase 3B, multicentre, randomized, double-masked, active-controlled study of patients aged 0-3 years who underwent uncomplicated cataract surgery in one eye, with/without intraocular lens implantation. Patients were randomized to receive difluprednate 0.05% four times daily or prednisolone acetate 1% for 14 days post surgery, followed by tapering for 14 days. Safety included evaluation of adverse events. Primary efficacy was the proportion of patients with an anterior cell grade of 0 (no cells) at day 14; secondary efficacy was a global inflammation score.ResultsForty patients were randomized to each treatment group. Adverse drug reactions included corneal oedema (difluprednate 0.5%, n=1; prednisolone acetate 1%, n=0) and increased intraocular pressure or ocular hypertension (n=2/group). Mean intraocular pressure values during treatment were 2-3 mm Hg higher with difluprednate 0.05% compared with prednisolone acetate 1%; mean values were similar between groups by the first week after treatment cessation. At 2 weeks post surgery, the incidence of complete clearing of anterior chamber cells was similar between groups (difluprednate 0.05%, n=30 (78.9%); prednisolone acetate 1%, n=31 (77.5%). Compared with prednisolone acetate 1%, approximately twice as many difluprednate 0.05%-treated patients had a global inflammation assessment score indicating no inflammation on day 1 (n=12 (30.8%) vs n=7 (17.5%) and day 8 (n=18 (48.7%) vs n=10 (25.0%).ConclusionsDifluprednate 0.05% four times daily showed safety and efficacy profiles similar to prednisolone acetate 1% four times daily in children 0-3 years undergoing cataract surgery.

Stereopsis in children with unilateral pseudophakia.

AIM: To evaluate stereoacuity and the factors that can influence stereopsis in children with unilateral pseudophakia. METHODS: Charts of 38 patients who were diagnosed as having unilateral cataract and underwent cataract extraction with primary intraocular lens implantation were retrospectively reviewed. Data were collected on gender, age, race, age at presentation and the surgery, cataract types, the presence of strabismus before and after cataract extraction, refractive error and the presence of anisometropia, best corrected visual acuity (VA) of both eyes and stereoacuity. RESULTS: Thirty-eight patients were divided into two groups. Group I had 21 patients whose stereopsis was better than 400 s of arc. Seventeen patients in group II had stereopsis poorer than 400 s of arc. The mean ages at presentation and surgery were 4.9 and 6.3 years in group I and 2.7 and 3.0 in group II, respectively (p = 0.046,0.007). Posterior lenticonus was the most common cataract type in both groups (p = 0.20). Strabismus was more frequently associated with group II. Those who had no strabismus before and after cataract surgery were 66.7% in group I and 47.1% in group II (p = 0.02). Fifty-two per cent of patients in group I had a VA of 20/40 or better, but in group II, only one patient had a VA of 20/40 (p<0.001). With a VA of 20/40 or better as the reference level, the odds of having good stereopsis decreased significantly if VA in the eye with the cataract was less than 20/60 based on the multiple regression logistic analysis (OR 0.03, p = 0.0027). CONCLUSION: Stereopsis was better in children with later manifesting cataracts, in the absence of strabismus and in cases with a good postoperative VA. The postoperative VA was the most important factor affecting the outcome of stereopsis in children with unilateral pseudophakia.

Optotype acuity and re-operation rate after unilateral cataract surgery during the first 6 months of life with or without IOL implantation.

AIMS: To compare optotype acuities and re-operation rates in children corrected with a contact lens (CL) compared with an intraocular lens (IOL) following unilateral cataract extraction during infancy in a non-randomised, retrospective case series. METHODS: 25 infants with a unilateral congenital cataract underwent cataract surgery with (IOL group, n = 12) or without (CL group, n = 13) IOL implantation when <7 months of age. Optotype acuities were assessed in 19 of these children at a mean age of 4.3 years (range 3.3-5.5 years). The number of re-operations were assessed in 21 children. RESULTS: The visual acuity results were similar in the two treatment groups (p = 0.99); however, two of the four (50%) children in the IOL group compared with two of the seven (28%) children in the CL group undergoing surgery during the first 6 weeks of life had 20/40 or better visual acuity. The children in the IOL group had more re-operations than the children in the CL group (mean 1.1 v 0.36). Most of the re-operations in the IOL group were membranectomies performed during the first year of life (median 8.0 months) whereas all of the re-operations in the CL group were the implantation of a secondary IOL later in childhood (mean 2.2 years). CONCLUSION: Optotype acuities were similar for the children corrected with a CL compared with IOL, while the children in the IOL group underwent more re-operations .

Management of ectopia lentis in children.

Marfan syndrome, homocystinuria, trauma, and simple ectopia lentis are the most common causes of pediatric lens subluxation. Many patients are best treated with a careful refraction of the phakic or aphakic pupillary axis. For those patients not achieving satisfactory refractive results, endocapsular lensectomy using modern automated vitreous cutting devices is relatively safe and successful. Given the lack of postoperative capsular support and our current level of intraocular lens technology, postoperative optical correction is most safely achieved with aphakic contact lenses or spectacles.

Endocyclophotocoagulation for management of difficult pediatric glaucomas.

INTRODUCTION: Experience with endoscopic diode laser cyclophotocoagulation remains limited. We report the efficacy and safety profile of this glaucoma surgery technique in the pediatric population. METHODS: Retrospective review of 51 endoscopic diode laser cyclophotocoagulation procedures performed on 36 eyes of 29 pediatric patients with glaucoma over a 6-year period. Surgery was performed by using the Microprobe (Endo Optiks, Little Silver, NJ) integrated laser endoscope system. Patients were followed-up for a minimum of 6 months or until declared treatment failures. Treatment success is defined as a postoperative intraocular pressure of < or = 21 mm Hg, with or without adjunctive glaucoma medications. RESULTS: Baseline mean pretreatment intraocular pressure was 35.06 +/- 8.55 mm Hg. Final postoperative intraocular pressure was 23.63 +/- 11.07 mm Hg (30% decrease) after an average of 1.42 +/- 0.87 endolaser procedures and 19.25 +/- 19.36 months of follow-up. Success rate of the initial procedure at last follow-up was 34%. Nine eyes (25%) were retreated at least once. Cumulative success rate after all procedures at last follow-up was 43%. Mean cumulative arc of treatment was 260 degrees +/- 58 degrees of ciliary processes. Postoperative complications included retinal detachment in 2 patients, hypotony in 1 patient, and progression of vision loss from hand motion to no light perception in 1 patient. All 4 complications occurred in aphakic patients. CONCLUSIONS: Endoscopic diode laser cyclophotocoagulation is a moderately effective procedure for the management of difficult pediatric glaucomas. Aphakic patients may have an increased risk of significant postoperative complications, such as retinal detachment.

A novel human homolog of eosinophil major basic protein.

Eosinophil major basic protein (MBP) contributes to host defense and disease pathophysiology. Chromosome 11 contains the genes for human MBP1 (hMBP1) and a second novel MBP, hMBP2, in the centromere to 11q12 region. Interestingly, greater similarity exists between human and murine MBP1 and MBP2 orthologs, respectively, than between hMBP1 and hMBP2, suggesting a gene duplication event prior to the divergence of humans and mice. There is abundant mRNA for hMBP1 in both bone marrow (eosinophils and basophils) and placenta, but hMBP2 mRNA is present only in bone marrow (eosinophils). Comparison of proximal promoters for hMBP2, hMBP1, and murine MBP1 (mMBP1) shows a conserved GATA transcription factor binding site (functionally active in hMBP1). However, whether a C/EBP binding site common to hMBP1 and mMBP1 is functionally conserved in hMBP2 remains unresolved. Similarly, the role of conserved putative IK2 and STAT binding sites in MBP transcriptional control remains unknown. Like hMBP1, hMBP2 is in the eosinophil secondary granule. However, hMBP2 is two-fold less positively charged than hMBP (+8 versus +16 at neutral pH), and this difference may explain hMBP2's similar, but often less potent, in vitro biological activities. Overall, while conservation of hMBP2's amino acid sequence (63% identity with hMBP1) suggests a common function(s) with hMBP1, hMBP2's substantially reduced charge and the existence of the similar mMBP2 argue for additional, unique functions for hMBP2.

A comparison of grating visual acuity, strabismus, and reoperation outcomes among children with aphakia and pseudophakia after unilateral cataract surgery during the first six months of life.

PURPOSE: The method of correcting aphakia after unilateral cataract extraction during infancy is controversial. Some authorities advocate correction with an intraocular lens (IOL) whereas others advocate correction with a contact lens (CL). We compared grating visual acuity, alignment, and reoperative outcomes in age-matched children treated with these 2 modalities at 5 clinical centers. METHODS: Twenty-five infants born in 1997 or 1998 with a dense unilateral congenital cataract who had cataract surgery coupled with (IOL group, n = 12) or without (CL group, n = 13) primary IOL implantation were enrolled in this study. All patients were prescribed half-time occlusion therapy. In July 1999, their grating visual acuities, ocular alignments, and reoperation rates were assessed. RESULTS: The mean grating visual acuity (LogMAR) for the affected eye was 0.70 +/- 0.32 for the IOL group and 0.87 +/- 0.31 for the CL group (P =.19). The mean interocular difference in grating visual acuity was 0.26 +/- 0.30 for the IOL group and 0.50 +/- 0.28 for the CL group (P =.048). The incidence of strabismus (>10 PD) was 75% in the IOL group compared with 92% in the CL group (P =.24). The incidence of reoperations was 83% in the IOL group compared with 23% in the CL group (P =.003). CONCLUSIONS: Our preliminary data suggest that correcting aphakia after unilateral congenital cataract surgery with primary IOL implantation results in an improved visual outcome but a higher rate of complications requiring reoperation. A randomized clinical trial, the Infant Aphakia Treatment Study, is planned to further study the optimal treatment for aphakia following unilateral cataract extraction during infancy.

Relationship of dissociated vertical deviation and the timing of initial surgery for congenital esotropia.

PURPOSE: To clarify the incidence of dissociated vertical deviation (DVD) among patients with congenital esotropia and to identify any relationship between the time when patients undergo their initial strabismus surgery and the time when they may subsequently have DVD develop. DESIGN: Noncomparative case series. PARTICIPANTS: One hundred five consecutive patients undergoing surgery for congenital esotropia over a 10-year period. METHODS: All patients underwent bimedial rectus recession before 24 months of age. MAIN OUTCOME MEASURES: Patients were followed postoperatively to note the age at onset of clinically evident DVD. RESULTS: By 6 years of age, 92% of available patients had DVD. The mean age at onset was 2.81 +/- 1.37 years. There was no significant difference between patients surgically aligned before 6 months of age compared with those aligned between 6 and 12 or 12 and 24 months of age. CONCLUSIONS: DVD occurs in almost all patients with surgically treated congenital esotropia, and its development is unrelated to the timing of surgical intervention during the first 24 months of life.

Comparative structure, proximal promoter elements, and chromosome location of the human eosinophil major basic protein genes.

Human eosinophil major basic protein (MBP) is strongly implicated as a mediator of disease, especially bronchial asthma. We recently isolated a highly divergent human homologue of MBP (MBPH). Given human MBP's importance in disease and the restricted expression of it and human MBPH, we isolated the 4.6-kb human MBPH gene (HGMW-approved symbol PRG3). Comparisons among the human MBP (PRG2), human MBPH, and murine MBP-1 (mMBP-1; Prg2) genes suggest that the human MBP and mMBP-1 genes are more closely related than either is to the human MBPH gene. Proximal promoters of these three genes show conservation of potential binding sites for IK2 and STAT and of a known GATA site. However, a known C/EBP site is altered in the human MBPH gene's proximal promoter. The human MBP and MBPH genes localized to chromosome 11 in the centromere to 11q12 region. Thus, the human MBP and MBPH genes have diverged considerably, probably following a gene duplication event. Furthermore, the identified conserved and distinct proximal promoter elements likely contribute to the eosinophil-restricted and relatively reduced transcription of the human MBPH gene.

Outpatient management of traumatic hyphemas in children.

OBJECTIVE: There are no outcome reports in the literature for outpatient management of traumatic hyphemas in children. Therefore we studied such cases at our institutions. DESIGN: Retrospective chart review. PARTICIPANTS: 25 children less than 16 years of age with grade I traumatic hyphemas. INTERVENTION: Inactivity at home with frequent office visits to monitor progress and complications. Treatment otherwise varied but virtually all patients received protective eye shields and topical steroids. MAIN OUTCOME MEASURES: Rate of rebleeding and final visual acuity. RESULTS: Three patients (12%) suffered a rebleed; one required surgery for clot evacuation. One of the three did not receive topical steroids and if he is excluded, rebleed rate is 2/24 or 8.3%. The hyphema resolved without sequelae in the other 22 patients. All patients had a final visual acuity of 20/40 or better except three patients (12%) who had concurrent vision-limiting ocular injuries and/or disease. Final visual acuity was 20/30 or better in all three patients with rebleeds. CONCLUSIONS: Our rebleed rate was within the broad range of rebleed rates reported in the literature. However, improved efforts to identify children at highest risk for rebleeding, to maximize compliance with treatments, and to consider systemic agents in selected cases, could further reduce the rebleed rate and increase acceptance and safety of outpatient management in pediatric traumatic hyphemas.

A comparison of the rate of refractive growth in pediatric aphakic and pseudophakic eyes.

OBJECTIVE: To compare the rate of refractive growth in pseudophakic children's eyes to that of aphakic eyes. DESIGN: Multicenter, retrospective observational case series. PARTICIPANTS: 83 patients with pseudophakic eyes (100 eyes) and 74 patients with aphakic eyes (106 eyes), with an age of surgery between 3 months and 10 years and a minimum follow-up time of 3 years or more, depending on the age at surgery. METHODS: A logarithmic model was used to analyze the rate of refractive growth for each eye. MAIN OUTCOME MEASURES: Age at surgery, intraocular lens power, intraocular lens A-constant, initial postoperative refraction, final refraction, and final age. RESULTS: Overall, pseudophakic eyes showed a lesser rate of refractive growth than aphakic eyes (-4.6 diopter vs. -5.7 diopter, P = 0.03). This trend was also present but less significant when the eyes were grouped into those less than 6 months of age at surgery (-3.3 diopter vs. -4.6 diopter, P = 0.09) and older patients (-5.0 diopter vs. -6.1 diopter, P = 0.07). However, the mean quantity of myopic shift was greater in pseudophakic eyes than in aphakic eyes (-5.26 diopter vs. -4.54 diopter), despite shorter follow-up times in the pseudophakic eyes. This is due to the optical effects of a constant intraocular lens power in a growing eye. CONCLUSIONS: Pediatric pseudophakic eyes have a slightly lesser rate of refractive growth than aphakic eyes. The new rate values should be used for predicting future refractions in these eyes.

Unilateral intraocular lens implantation during the first six months of life.

PURPOSE: The purpose of this study was to determine the incidence of postoperative complications and the occurrence of myopic shift in infantile eyes after cataract surgery and implantation of an intraocular lens (IOL). METHODS: Cataract surgery and IOL implantation was performed on 11 infants with unilateral congenital cataracts who had a mean age of 10+/-6 weeks at 5 clinical centers. IOLs with a mean power of 26.2+/-2.3 D were implanted using a standardized protocol. The infants were then followed up for a mean of 13+/-6 months for postoperative complications and longitudinal changes in their refractive error. RESULTS: Eight of the 11 eyes had postoperative complications and were treated with a reoperation. Complications included open-angle glaucoma (n = 2), lens reproliferation into the visual axis (n = 2), pupillary membranes (n = 2), and corectopia (n = 2). A younger age at the time of surgery was positively correlated with the development of a postoperative complication requiring a reoperation (P = .03). A mean myopic shift of 5.49 D occurred in these eyes a year after surgery. No preoperative factors could be identified that correlated with the magnitude of the myopic shift. CONCLUSION: IOL implantation during infancy is associated with a high complication rate frequently requiring reoperation. A large myopic shift typically occurs that necessitates an initial or a late overcorrection with spectacles or a contact lens, depending on the power of the IOL implanted. Until ongoing randomized trials are completed, we recommend that surgeons exercise caution before implanting IOLs in the eyes of infants.

Congenital malignant rhabdoid tumor of the orbit.

Malignant rhabdoid tumor is a rare and highly malignant renal tumor of infancy. Extrarenal tumors involving the orbit have been reported, but never at birth. The authors describe a primary malignant rhabdoid tumor of the orbit in a neonate who had massive unilateral proptosis at birth. Clinical, radiographic, and histologic features of the tumor are discussed.

Results of early alignment of congenital esotropia.

OBJECTIVE: To determine the long-term motor and sensory results after early surgical correction of patients with congenital esotropia. DESIGN: Noncomparative interventional case series. PARTICIPANTS: Ten infants with congenital esotropia. INTERVENTION: Patients had bimedial rectus recession between 83 and 159 days of age; were re-examined in a regular follow-up program; and were retreated when required for strabismus, amblyopia, and refractive errors. MAIN OUTCOME MEASURES: Final alignment, stereo acuity, variations in vision, alignment, refraction, and number and types of retreatments required during the period of observation. RESULTS: All patients were aligned initially with bimedial rectus recession of 8.0 to 10.0 mm measured from the limbus. A total of 11 additional surgical procedures were performed on 7 patients to maintain alignment. Four patients required hyperopic spectacle correction to maintain alignment, and two patients required short periods of patching. Visual acuity was 20/40 or better in 19 eyes at the most recent examination, which was between 8.3 and 11.8 years after initial surgery. All patients had final alignment to within 10 prism diopters (PD) of orthotropia at either distance or near. Nine of ten patients had dissociated vertical deviation (DVD), and four of ten patients had latent nystagmus. Four patients had measurable stereo acuity at their last visit, with two achieving a stereo acuity of 3000 seconds (the Titmus fly), one 400 seconds, and one 140 seconds. CONCLUSION: Surgical alignment of congenital esotropia can be achieved in the 4-month-old with bimedial rectus recession, but this does not ensure continued alignment. At least one additional surgical procedure is required on average to maintain alignment in the first 10 years after initial successful surgery. These patients can also be expected to have one or more of the following: DVD, latent nystagmus, refractive component, or latent strabismus. Regardless of outcome, patients with congenital esotropia have optokinetic asymmetry. Attainment of stereo acuity, including high-grade stereo acuity, may be enhanced by attainment of orthotropia or small-angle esotropia but is likely to be ultimately dependent on constitutional factors rather than age of alignment.

Intermediate-term results of endoscopic diode laser cyclophotocoagulation for pediatric glaucoma.

INTRODUCTION: Endoscopic diode laser cyclophotocoagulation (EDLC) is a new treatment modality for glaucoma. Experience with this surgical procedure in children is limited. We report our results after 3 years of follow-up and review the safety of this procedure in pediatric patients. METHODS: EDLC was performed on 10 eyes of 8 children who had either aphakic glaucoma or refractory congenital glaucoma. Patients were treated in 2 groups. An initial group of 5 eyes with poor visual prognosis underwent a conservative treatment of no more than 180 degrees of ciliary processes. After an observational period, a second group of 5 eyes with better visual potential was treated more aggressively. Most eyes in the second group received cyclophotoablation to 270 degrees of ciliary processes. Patients were followed up until time of failure or for a minimum of 3 years. RESULTS: At 3 years of follow-up, 50% of eyes that received a single treatment of endolaser had an intraocular pressure (IOP) of < or =22 mm Hg with or without glaucoma medications. Twenty percent had an IOP < or =22 mm Hg without any glaucoma medications. Five eyes were treated successfully with a mean IOP of 17.8 +/- 3.4 mm Hg at 36 months of follow-up. The remaining 5 eyes were considered treatment failures with postoperative IOPs >22 mm Hg, despite adjunctive glaucoma medications. Mean time to treatment failure was 10.5 months (range, 3.7-22.2 months). No sight-threatening complications occurred. None of the eyes became hypotonus or caused undue discomfort during the postoperative period. CONCLUSION: EDLC is a relatively safe and effective procedure for the management of difficult pediatric glaucoma. Results are comparable to other cyclodestructive modalities. Although not observed in this study, it should be cautioned that phakic eyes might be at increased risk for surgical complications.

A novel and highly divergent homolog of human eosinophil granule major basic protein.

Eosinophils are important effector cells in defense against helminth infection and in allergic diseases. To identify novel eosinophil proteins, large scale sequencing of a cDNA library prepared from interleukin-5-stimulated umbilical cord precursor cells was performed, and the major genes expressed by maturing eosinophils were determined. This resulted in the identification of a cDNA with 64% identity to human prepro-major basic protein (hprepro-MBP). This cDNA was designated hprepro-MBP homolog (hprepro-MBPH). Interestingly, the calculated pI values for hMBPH and hMBP differed by >100-fold, with pI values of 8.7 and 11.4, respectively. Given this pronounced basicity difference, the homolog transcript's abundance (1.1%), and MBP's critical role in eosinophil biological activity, we further characterized the homolog. Reverse transcription-polymerase chain reaction detected transcription of hprepro-MBPH in bone marrow only, and this result was confirmed by analysis of a large cDNA data base (electronic Northern). hMBPH was isolated from human eosinophil granule lysates, and its identity was verified by amino acid sequencing and by mass spectrometry. Analyses of the biological activities showed that hMBPH had effects similar to hMBP in cell killing and neutrophil (superoxide anion production and interleukin-8 release) and basophil (histamine and leukotriene C4 release) stimulation assays, but usually with reduced potency. Overall, this novel homolog's unique physical properties indicated that the high net positive charge of hMBP is important but not essential for biological activity.

Early strabismus surgery for thyroid ophthalmopathy.

OBJECTIVE: To determine whether strabismus surgery during active thyroid ophthalmopathy is beneficial for selected patients. DESIGN: Case series. PARTICIPANTS: Eight patients with severe restrictive strabismus due to thyroid ophthalmopathy underwent early strabismus surgery and were followed for a minimum of 16 months after their initial surgery. INTERVENTION: All eight patients underwent strabismus surgery while their thyroid ophthalmopathy was evolving. MAIN OUTCOME MEASURES: Success was determined by the ability to fuse in the primary position at distance and near without an abnormal head position, and the absence of vision-threatening complications related to strabismus surgery. RESULTS: All eight patients achieved successful long-term alignment. Four patients (50%) required more than one operation. CONCLUSIONS: Strabismus surgery during active thyroid ophthalmopathy can result in long-term stable alignment and may be a useful alternative in selected patients with marked disability due to thyroid ophthalmopathy.