Ken K. Nischal

Indications and Outcomes of Deep Anterior Lamellar Keratoplasty in Children

PURPOSEnTo report our experience of deep anterior lamellar keratoplasty (DALK) in children.nnnDESIGNnRetrospective case note review.nnnPARTICIPANTSnNine patients (13 eyes) aged from 13 weeks to 14 years, 11 months at the Clinical and Academic Department of Ophthalmology, Great Ormond Street Hospital for Children National Health Service (NHS) Trust, London, United Kingdom.nnnMETHODSnA study of all pediatric patients undergoing DALK from February 2002 to October 2008 was undertaken. Deep anterior lamellar keratoplasty was attempted in 9 children (13 eyes); the procedure was successful in 11 eyes, and 2 eyes progressed to penetrating keratoplasty (PKP). One eye underwent repeat DALK. Preoperative examination included electrophysiology, ultrasound biomicroscopy (UBM), and slit-lamp biomicroscopy.nnnMAIN OUTCOME MEASURESnComplications and visual acuity at last follow-up.nnnRESULTSnFive patients had mucopolysaccharidoses (MPS), 3 patients had scarring presumed to be infectious, and 1 patient had keratoconus. Because of the failure of follow-up and loose sutures, 1 child with MPS had an epithelial rejection and the operation was repeated successfully. All grafts showed good graft clarity 10 to 80 months after grafting with visual acuities ranging from 0.28 to 1.0 logarithm of the minimum angle of resolution. Two children with nonspecific causes of scarring showed good visual acuities 24 to 51 months post-DALK. Two children who had conversion to PKP were lost to follow-up because they had moved abroad. In 4 of the 5 children with MPS, established techniques of DALK could not be performed because of excessive glycosaminoglycans (GAGs) in the stroma. Ultrasound biomicroscopy was used to guide trephination depth in the first instance. In 1 child with MPS, viscodissection was successfully used. All clinically diagnosed scars were histologically confirmed, and electron microscopy of corneal buttons confirmed the diagnosis in patients with MPS.nnnCONCLUSIONSnDeep anterior lamellar keratoplasty should be considered in children with MPS and partial-thickness scars. In MPS, viscodissection and the big bubble technique may not be useful if there are excessive GAGs in the stroma.nnnFINANCIAL DISCLOSURE(S)nProprietary or commercial disclosure may be found after the references.

Childhood optic neuritis clinical features and outcome

Aim To describe clinical features and outcome of a series of children with first-episode optic neuritis investigated in three paediatric neurology centres. Methods Databases were searched to identify children (<16 years) with optic neuritis and life table analysis was used. Results 44 children (female/male ratio 1.8) median age 10.9 years were followed up for median 1 year. Optic neuritis was unilateral in 43%. Maximal visual deficit was severe (<6/60) in 77%, with full recovery in 70%. Cumulative probability of developing MS (11/44) or NMO (3/44) at 2 years was 0.45. Relapsing optic neuritis was a strong predictor for development of MS or NMO. A positive MRI (>1 brain T2 hyperintense lesion) was a strong predictor for development of MS. Discussion Childhood optic neuritis is associated with severe visual deficit with good recovery. An initial abnormal MRI brain scan or relapsing optic neuritis should alert the clinician to MS or NMO diagnosis.

Cataract surgery and primary intraocular lens implantation in children ⩽2 years old in the UK and Ireland: finding of national surveys

Background: Current patterns of practice relating to primary intraocular lens (IOL) implantation in children ⩽2 years old in the UK and Ireland are investigated. Methods: National postal questionnaire surveys of consultant ophthalmologists in the UK and Ireland. Results: 76% of 928 surveyed ophthalmologists replied. 47 (7%) of the respondents operated on children aged ⩽2 with cataract. 41 (87%) of respondents performed primary IOL implantation, but 25% would not implant an IOL in a child under 1 year old. 88% of surgeons used limbal wounds, 80% manual capsulotomies, 98% posterior capsulotomies and 100% hydrophobic acrylic lenses. The SRK/T formula was most commonly used (70%). Exclusion criteria for primary IOL implantation varied considerably and included microphthalmos (64% of respondents), anterior and posterior segment anomalies (53%, 58%), and glaucoma (19%). Discussion: Primary IOL implantation in children ⩽2 has been widely adopted in the UK and Ireland. There is concordance of practice with regards to surgical technique and choice of IOL model. However, there is some variation in eligibility criteria for primary IOLs: this may reflect a lack of consensus on which children are most likely to benefit. Thus, there is a need for systematic studies of the outcomes of primary IOL implantation in younger children.

CYP1B1-Related Anterior Segment Developmental Anomalies: Novel Mutations for Infantile Glaucoma and Von Hippel's Ulcer Revisited

PURPOSEnTo determine the prevalence of CYP1B1 mutations in a cohort of patients with congenital corneal opacification (CCO), infantile glaucoma, or both and to describe a developmental CCO associated with CYP1B1 mutation that may explain von Hippels original description of an internal ulcer.nnnDESIGNnRetrospective genotyping of a cohort of patients with infantile glaucoma and CCO.nnnPARTICIPANTSnThirty-three patients with CCO, infantile glaucoma, or both.nnnMETHODSnAll patients underwent a full clinical evaluation with or without examination under anesthetic including anterior segment photography, ultrasound biomicroscopy (for CCO patients; n = 22), and histopathologic analysis in patients in whom penetrating keratoplasty (PK) was performed (n = 10). Patient DNA and DNA from 50 normal control individuals who had undergone a full ophthalmologic examination were screened for CYP1B1 mutations.nnnMAIN OUTCOME MEASURESnClassification of the developmental corneal opacity phenotype in infantile glaucoma patients with CYP1B1 mutations.nnnRESULTSnNine distinct pathogenic recessive CYP1B1 mutations were found in 11 patients from 6 unrelated families, including 1 patient with an entire deletion of the CYP1B1 gene. Two of these patients, including the patient with the deletion, had isolated infantile congenital glaucoma with no other abnormalities. No CYP1B1 mutations were found in another 13 patients (7 of whom underwent PK in at least 1 eye) who had CCO with iridocorneal or keratolenticular adhesions (Peters anomaly types I and II, respectively). Eight further children with CYP1B1 mutations who had CCO from birth and glaucoma underwent successful glaucoma treatment but had persistent diffuse CCO without iridocorneal or keratolenticular adhesions. Three of these underwent bilateral PK, and the histologic results were not consistent with any hitherto recognized congenital corneal dystrophy and showed abnormalities of the central corneal endothelium.nnnCONCLUSIONSnBoth severe CCO and isolated infantile glaucoma are associated with CYP1B1 mutations. The severe CCO phenotype reported herein often requires PK and has typical histopathologic changes. The mutations associated with this phenotype have not been reported previously. This phenotype may explain the patient described by Von Hippel in 1897.

Functional analysis of FOXE3 mutations causing dominant and recessive ocular anterior segment disease.

Mutations in FOXE3 are associated with both recessive and dominant inheritance of severe anterior ocular malformations and glaucoma. However, functional analyses of putative pathogenic mutations have not been performed. We tested the hypothesis that variations in FOXE3 activity underlie the different modes of inheritance and disease phenotype. In band shift assays, three recessive mutants showed loss‐of‐function, one retained DNA binding activity, whereas two dominant mutants showed altered activity. All six mutants showed reduced transactivation function compared with wild‐type, and modeling the heterozygous state resulted in an intermediate level of activity providing no evidence for dominant negative action. Our in vitro data are consistent with loss‐of‐function below a dosage sensitive threshold as a mechanism of action for recessive mutations, but indicate an altered mutant protein function rather than a haploinsufficient mechanism for dominant mutations. This study provides the first functional evidence demonstrating that FOXE3 mutations identified in patients impair protein function with differential effects.

The use of punctal plugs in children

Background/aims To evaluate the safety and efficacy of punctal plugs in children with dry eye syndrome. Methods A retrospective case series of patients who had an insertion of silicone punctal plugs for dry eye syndrome. Data collected included presenting symptoms, signs, systemic disorders if present, type of anaesthesia and complications by the time of last follow-up. Results Twenty-five patients (median age at insertion 7u2005years, range 1.5–13.8u2005years) were identified. Median follow-up was 18u2005months. The commonest symptoms were photophobia, soreness and blepharospasm, and the commonest sign was punctate epithelial erosions. Concurrent systemic disease was present in 18/25 patients. Repeated procedures were carried out in eight of 25 patients. Twenty-four of 35 insertions were performed under general anaesthesia. A substantial improvement in ocular surface disease was noted in all cases: frequency of lubricant use was reduced in eight of 25 and visual acuity improved in 15/25 patients. Spontaneous extrusion was the commonest complication and occurred within 6u2005months in 19% of cases. Conclusion Dry eye syndrome in children is often accompanied by systemic disease, so in a child with persistent symptoms this should be explored. Punctal plugs offer a safe and effective form of treatment especially as compliance of frequent lubrication is limited in children.

The Frequency of Signs of Meibomian Gland Dysfunction in Children with Epidermolysis Bullosa

PURPOSEnTo determine the frequency of meibomian gland dysfunction (MGD) in children with epidermolysis bullosa (EB).nnnDESIGNnHospital-based cross-sectional study.nnnPARTICIPANTSnOne hundred five children with different forms of EB.nnnMETHODSnProspective ophthalmic examination of children with EB presenting over seventeen months including meibomian gland assessment using a recognized classification.nnnMAIN OUTCOME MEASURESnFrequency of MGD.nnnRESULTSnOne hundred five children were recruited, 8.6% with junctional EB, 34.3% with simplex EB, 34.3% with autosomal recessive dystrophic EB, and 22.9% autosomal dominant dystrophic EB. Mean age was 7.42 years (range, 0.08-17.75 years). Ninety-two children (87.62%) demonstrated 1 or more features of MGD.nnnCONCLUSIONSnMost children with EB exhibit signs of MGD. To the best of our knowledge, this is the first prospective ocular surface evaluation in children with EB to include lid margin evaluation using a recognized classification system. Our findings help explain some of the ocular surface anomalies seen in children with EB.

Atypical Peters plus syndrome with new associations

1. IngMR. Outcome study of surgical alignment before six months of age for congenital esotropia. Ophthalmology 1995;102:2041-5. 2. Ing MR. Botulinum alignment for congenital esotropia. Trans Am Ophthalmol Soc 1992;90:361-7. 3. McNeer KW, Tucker MG, Guerry CH, Spencer RF. Incidence of stereopsis after treatment of infantile esotropia with botulinum toxin A. J Pediatr Ophthalmol Strabismus 2003;40:288-92. 4. Tejedor J, Rodriguez JM. Management of nonresolving consecutive exotropia following botulinum toxin treatment of childhood esotropia. Arch Ophthalmol 2007;125:1210-13. 5. Birch EE, Wang J. Stereoacuity outcomes after treatment of infantile and accommodative esotropia. Optom Vis Sci 2009;86:647-52. 6. Ruiz MF, Alvarez MT, Sanchez-Garrido CM, Hernaez JM, Rodriguez JM. Surgery and botulinum toxin in congenital esotropia. Can J Ophthalmol 2004;39:639-49.

Maternal drug abuse and ocular morbidity: more than meets the eye?

In this issue, Hamilton et al 1 and Gupta et al ,2 from two different Scottish centres, describe the ocular findings in cohorts of children who had been exposed to opiates, including methadone, or benzodiazepines in utero. Both groups make compelling arguments for opiate use, and possibly benzodiazepine use, resulting in visual pathway and visuomotor abnormalities with one group utilising visual electrophysiology. Gupta et al go so far as stating that “…we must conclude that these substances have teratogenic effects alone and particularly when used in combination”.nnThe teratogenic effect of opiates in animal models (namely diamorphine hydrochloride, methadone hydrochloride and the synthetic enkephalin analogue FK 33-824) was first observed in 19853 and included a neurotropic syndrome of malformations restricted to the central nervous system if administered during the critical period of neural tube closure. Pretreatment with corresponding equimolecular doses of the antagonist naloxone hydrochloride …