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.

Factors associated with stereopsis and a good visual acuity outcome among children in the Infant Aphakia Treatment Study.

PurposeTo identify factors associated with stereopsis in children with good visual acuity after unilateral congenital cataract surgery in the Infant Aphakia Treatment Study.Patients and methodsInfants with a unilateral congenital cataract (n=114) were randomized to IOL implantation or contact lens correction after cataract surgery. At age 4.5 years, a masked examiner assessed HOTV acuity and stereopsis. Adherence to patching was assessed using 48-h recall telephone interviews and 7-day diaries throughout the first 5 years of life. Ocular motility was evaluated at age 5 years. Baseline, postoperative, and adherence findings were compared between patients with 20/40 or better acuity in their treated eyes with or without stereopsis.ResultsThirty (27%) of 112 patients who were evaluated at age 4.5 years had 20/40 or better acuity in their treated eye. Stereopsis was present on one or more tests in 15 of these 30 (50%) children. Baseline characteristics and postoperative findings did not differ between patients with or without stereopsis. Children with stereopsis were more likely to be orthotropic at distance (P=0.003) and were patched for fewer hours per day throughout the first 5 years of life and the difference increased over time (P<0.001). On average children with stereopsis were patched for 3.4 h/day during the first year of life and patching steadily decreased to 1.8 h/day by age 4 years.ConclusionAmong children with good vision following unilateral congenital cataract surgery, orthophoria and fewer hours of patching, particularly during years 2, 3, and 4, are associated with some evidence of stereopsis.

Associated systemic and ocular disorders in patients with congenital unilateral cataracts: the Infant Aphakia Treatment Study experience.

PurposeFive-year prospective data on children enrolled in the Infant Aphakia Treatment Study (IATS) provided an opportunity to explore ocular and systemic associations in patients with a unilateral congenital cataract.MethodsInfants <7 months of age with a unilateral cataract were eligible for IATS screening. We reviewed data pertaining to the exclusion of patients as well as data collected on standardized study forms used at any time for documentation of ocular or systemic disorders.ResultsOverall, 227 infants were referred for possible enrollment. Of these, 10 had insignificant cataracts and 32 refused to participate. Of those excluded, 3 were premature, 27 had significant ocular disease (usually persistent fetal vasculature (PFV) or corneal diameter <9 mm), and 4 had systemic disorders. An additional 26 were excluded at the time of the first EUA, most often because of PFV or variants thereof. On follow-up, in the 114 enrolled patients, the following disorders were diagnosed: Stickler syndrome (1), mitochondrial disease (1), autism (1), and presumed congenital rubella syndrome (1). No patient developed a cataract in the fellow eye.DiscussionSome conditions that can feature unilateral cataracts are diagnosed at birth or very early in life, but others may be diagnosed at varying periods thereafter. PFV and its variants are the most common associated ocular findings in about a quarter of cases of unilateral congenital cataracts.ConclusionAlthough patients with a unilateral cataract may have significant associated abnormalities in the affected eye, most commonly PFV and its variants, the prevalence of associated significant systemic disease is quite low.

Key differences identified between actinic keratosis and cutaneous squamous cell carcinoma by transcriptome profiling.

BACKGROUND: Cutaneous squamous cell carcinoma (cSCC) is one of the most common malignancies in fair-skinned populations worldwide and its incidence is increasing. Despite previous observations of multiple genetic abnormalities in cSCC, the oncogenic process remains elusive. The purpose of this study was to elucidate key molecular events associated with progression from premalignant actinic keratoses (AKs) to invasive cSCC by transcriptome profiling. METHODS: We combined laser capture microdissection with the Affymetrix HGU133 Plus 2.0 microarrays to profile 30 cSCC and 10 AKs. RESULTS: We identified a core set of 196 genes that are differentially expressed between AK and cSCC, and are enriched for processes including epidermal differentiation, cell migration, cell-cycle regulation and metabolism. Gene set enrichment analysis highlighted a key role for the mitogen activated protein kinase (MAPK) pathway in cSCC compared with AK. Furthermore, the histological subtype of the tumour was shown to influence the expression profile. CONCLUSION: These data indicate that the MAPK pathway may be pivotal to the transition from AK to cSCC, thus representing a potential target for cSCC prevention. In addition, transcriptome differences identified between cSCC subtypes have important implications for future development of targeted therapies for this malignancy.

Cryptic cerebral visual impairment in children.

AIM: To review the medical records of seven children with a delayed diagnosis of cerebral visual impairment. METHODS: The charts of a consecutive series of children examined in a university based ophthalmology clinic with a delayed diagnosis of cerebral visual impairment were reviewed. Their neuroimaging studies were evaluated by a paediatric neuroradiologist. RESULTS: The seven patients ranged in age from 2 years to 10 years at the time of presentation and had acuities ranging from 20/40 to 20/400. Their visual fields ranged from full visual fields to homonymous hemianopias. Neuroimaging findings ranged from subtle occipital lobe abnormalities to obvious cerebral volume loss. CONCLUSIONS: Cerebral visual impairment can be cryptic in children with mild visual impairment. Neuroimaging studies and visual field testing can help to differentiate this condition from other causes of visual impairment.

Longitudinal changes in the spherical equivalent refractive error of children with accommodative esotropia.

AIM: To assess the longitudinal changes in the spherical equivalent (SE) refractive errors of children with accommodative esotropia as a function of the age when glasses were prescribed. METHODS: Refractive errors were followed longitudinally for 126 children with accommodative esotropia for a mean of 4.4 (SD 2.5) years. Cycloplegic refractions were performed using an autorefractor for older children and retinoscopy for younger children. The refractive data were analysed for three groups of children based on their age at the time spectacles were prescribed. RESULTS: The initial SE refractive error was age dependent (<2 years, 5.1 (1.9) D; 2-<4 years, 4.2 (1.9) D; 4-8 years, 3.8 (1.7) D). Children in all age groups had an initial increase in their SE refractive error, followed by a later decrease; however, the greatest decrease occurred in the patients in the oldest age group. The SE refractive error peaked 1 year after spectacles were prescribed for the children 4-8 years of age versus 6 years after spectacles were prescribed for the children less than 2 years of age. CONCLUSION: Longitudinal changes in SE refractive error for children with accommodative esotropia vary as a function of their age when spectacle wear is initiated.

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 .

Weaning children with accommodative esotropia out of spectacles: a pilot study.

BACKGROUND/AIM: Many children with accommodative esotropia must continue spectacle use throughout life. This study was undertaken to determine which factors are predictive of successfully weaning children with accommodative esotropia out of spectacles. METHODS: A retrospective review of 10 children with accommodative esotropia, who were gradually weaned from their hyperopic correction, and three age matched controls was performed. The main outcome measure was resolution or non-resolution of esotropia following weaning and eventual discontinuation of spectacles. Secondary outcome measures were final refractive error and the final esotropic or esophoric angle without correction. RESULTS: Six patients were successfully weaned from spectacles. At the completion of the weaning period one child was orthophoric and the other five children had well controlled esophorias. The other four patients remained spectacle dependent because of persistent esotropia or decreased vision without spectacles. The baseline and final refractive errors were significantly lower in the children successfully weaned from spectacles (p = 0.014). While the children who were successfully weaned from spectacles were older when initially diagnosed with accommodative esotropia (4.6 v 2.5 years), this difference was not statistically significant (p = 0.09). CONCLUSION: Some children with accommodative esotropia may be weaned out of spectacles during the grade school years with resolution of their esotropia. It is likely that gradual reduction of the hyperopic correction increases divergence amplitudes, but it is unclear whether this facilitates emmetropisation.

Accommodative esotropia.

Accommodative esotropia is the most common type of strabismus with a very favorable prognosis if the appropriate treatment is initiated promptly. Spectacles remain the preferred treatment, but both contact lenses and refractive surgery may be helpful in some situations to correct the associated hyperopia. Strabismus surgery should only be used if optical correction or refractive surgery are ineffective in restoring normal ocular alignment.

Slipped and lost extraocular muscles.

A slipped or lost muscle should be considered in the differential diagnosis of a patient presenting with a marked limitation of duction and inability to rotate the eye beyond the midline. Loss of a rectus muscle can occur after strabismus surgery, trauma, paranasal sinus surgery, orbital surgery, or retinal detachment surgery. The extraocular rectus muscle most frequently slipped or lost is the medial rectus muscle. Forced ductions, active force generation, saccadic velocity studies, differential intraocular pressure measurements, and orbital imaging studies may aid in identifying a slipped or lost muscle. However, no single diagnostic test provides absolute reliability for determining a lost muscle. Slipped muscles develop when the muscular capsule is imbricated without including the muscle or muscle tendon during strabismus surgery. When the capsule is reattached to the sclera, the tendon and muscle are then free to slip posteriorally from the site of attachment. Slipped muscles are retrieved by following the thin avascular muscle capsule posteriorally until the muscle is identified. A lost muscle can be found using a traditional conjunctival approach, by an external orbitotomy, or by an endoscopic transnasal approach. Although many diagnostic maneuvers are useful in identifying a lost rectus muscle, the oculocardiac reflex is the most important. Once the lost muscle is identified, the muscle should be imbricated with a nonabsorbable synthetic suture and securely reattached to the globe.

Peters' anomaly. A synopsis of surgical management and visual outcome.

Peters' anomaly is not an isolated anterior segment abnormality, but occurs as a diverse, phenotypically heterogeneous condition associated with multiple underlying ocular and systemic defects. Surgical treatment of Peters' anomaly is a complex and challenging undertaking. The broad spectrum of disease severity, the lack of uniformity in clinical features, the differences and overlap of preoperative risk factors, and the variability in the numbers and types of intraocular procedures that are performed on individual eyes, as well as postoperative complications all contribute to the difficulties involved in surgical management. This article discloses useful information pertaining to keratoplasty for Peters' anomaly. The study by Yang et al showed that long-term graft clarity could be achieved in 36% of eyes. However, 93% of all clear grafts were first grafts, whereas only 7% were second grafts. All third or subsequent grafts failed. Other important findings were: (1) the significantly greater chance of maintaining a clear graft with initial grafts, compared with subsequent grafts; (2) the disclosure of periods of differential risk for graft failure; and (3) the identification of risk factors for graft failure. Surgical intervention involving one or more procedures is effective in controlling IOP in 32% of eyes with associated congenital glaucoma. Still, multiple procedures and adjunctive medical therapy are often required to achieve and maintain adequate IOP control. The visual outcome is guarded in children with Peters' anomaly. Achieving a satisfactory visual outcome and preventing further visual loss is impeded by the presence of congenital anterior and posterior segment anomalies, structural defects of the CNS, cognitive dysfunction and amblyopia, as well as postoperative complications such as graft failure, cataract, inoperable retinal detachment, and phthisis.

Pediatric cataracts.

The management of infantile cataracts continues to be a challenging task, however with new surgical techniques, IOL implantation, and new patching regimens, the visual outcomes are improving.

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.

Retrieval of lost medial rectus muscles with a combined ophthalmologic and otolaryngologic surgical approach.

PURPOSE: To report retrieval of a medial rectus muscle completely detached from the globe and lost in the orbital tissue in four eyes. METHOD: A lost medial rectus muscle was retrieved in four eyes of four patients with either a transcutaneous medial orbitotomy approach or a transnasal endoscopic ethmoid sinus approach. RESULTS: The lost medial rectus muscle was successfully retrieved in all four patients. One patient lost the medial rectus muscle secondary to trauma, and the other three cases resulted from complications of strabismus surgery. The mean preoperative angle of exotropia was 44 prism diopters. The endoscopic approach was attempted in three patients, and the medial rectus muscle was successfully found in two of these patients. In one case in which the endoscopic approach was used, an image guidance system was used to aid in finding the lost medial rectus muscle. The endoscopic approach was abandoned in one case in which the medial rectus muscle could not be identified after extensive searching, but the muscle was subsequently found by means of the transcutaneous medial orbitotomy approach. A transcutaneous medial orbitotomy alone was used to find the lost medial rectus muscle in one of the cases. The postoperative ocular deviation for primary position at distance fixation was a mean of 24 prism diopters of exotropia. With one additional operation in two patients, the mean ocular deviation was less than 12 prism diopters. CONCLUSION: We successfully retrieved a lost medial rectus muscle in four patients with the use of nontraditional strabismus surgical techniques. We effectively combined techniques taken from both ophthalmology and otorhinolaryngology to help solve this difficult problem.

Isolated comitant esotropia and Chiari I malformation.

PURPOSE: To report four patients with isolated comitant esotropia and Chiari I malformation and discuss the most appropriate management. METHODS: Case reports and literature review. RESULTS: All four patients (5, 14, 16, and 37 years of age) presented with an isolated comitant esotropia that led to the diagnosis of Chiari I malformation. The first two patients underwent uncomplicated neurosurgical decompression of their malformation, followed by complete resolution of their esotropia. The third patient underwent strabismus surgery and experienced initial resolution of the esotropia, but eventual recurrence resulted in the strabismus surgery being repeated 5 years later. The fourth patient had strabismus surgery with resolution of the esotropia but only 2 months of follow-up. CONCLUSION: Although management of patients with Chiari I malformation and severe neurologic findings typically includes surgical decompression, management is less straightforward in cases with subtle findings or in which ocular findings are isolated. The decision to perform neurosurgical decompression or strabismus surgery should still be made on a case-by-case basis, with the understanding that strabismus surgery may provide only temporary ocular alignment.

Tonic pupil associated with congenital neuroblastoma, Hirschsprung disease, and central hypoventilation syndrome.

PURPOSE: To report the association of tonic pupil, congenital neuroblastoma, Hirschsprung disease, and central hypoventilation syndrome. METHODS: Case reports. RESULTS: Two infants with central hypoventilation syndrome and Hirschsprung disease were evaluated for dilated, nonreactive pupils present since birth. In both cases, pharmacologic testing with dilute pilocarpine confirmed denervation supersensitivity consistent with tonic pupil. The diagnosis of congenital neuroblastoma was subsequently established in both infants. CONCLUSIONS: The close association of these conditions in these two young children supports the concept of a common neural crest abnormality being present. A careful systemic evaluation to rule out congenital neuroblastoma should be performed in any young child who presents with tonic pupil in the setting of central hypoventilation syndrome and Hirschsprung disease.

Cataract and phthisis bulbi after laser photoablation for threshold retinopathy of prematurity.

PURPOSE: To describe the visual and structural outcome of eyes that developed a dense cataract after laser photoablation for threshold retinopathy of prematurity. METHODS: A retrospective review of eight consecutive infants who developed dense cataract(s) after bilateral laser photoablation for threshold retinopathy of prematurity. Of the 10 eyes with cataract, five eyes were treated with a diode laser and five with an argon laser. The stage and zone of the retinopathy of prematurity, number of burns applied, time of onset of the cataract, clinical findings at the time of cataract surgery, and the course after cataract surgery were reviewed. RESULTS: Six eyes had zone 1 disease and four had zone 2 disease. The mean number of burns applied per eye was 2532 +/- 856 (range, 1400 to 4500). A cataract was diagnosed a median of 3 [corrected] weeks (range, 1 to 28 weeks) after laser photoablation. Nine of the 10 cataracts were sufficiently dense to preclude a view of the fundus. All 10 eyes had clinical signs suggestive of an inflammatory or ischemic process that included one or more of the following findings: corneal edema, pupillary membrane, iris atrophy, depigmentation of ciliary processes, pigment on the anterior lens surface, posterior synechiae, hyphema, and shallow anterior chamber. Nine eyes underwent cataract surgery. Five of the 10 eyes had retinal detachment ranging in severity from stage 4A to stage 5 at the time of cataract surgery. Nine of the 10 eyes progressed to phthisis bulbi and no light perception. CONCLUSIONS: A dense cataract developing in the eye of an infant after laser photoablation for threshold retinopathy of prematurity is associated with a poor visual prognosis. The constellation of associated clinical findings appears to be most consistent with anterior segment ischemia.