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Examination of pupil reflections, also known as the red reflex text, can reveal problems in the cornea, lens and sometimes the vitreous, and is particularly useful in young children. These photographs show what can occur in the case of certain major eye conditions, the most serious of which is retinoblastoma.

Background: Adjuvant use of laser with systemic chemotherapy for treatment of retinoblastoma may reduce recurrence rates while also causing local side effects. Information is lacking on the effect of laser on visual outcomes., Methods: A retrospective review of two retinoblastoma centres in the United Kingdom was conducted. Patients were included if there was a macular tumour in at least one eye. Eyes that received chemotherapy alone were compared with eyes that received chemotherapy plus adjuvant laser., Results: A total of 76 patients and 91 eyes were included in the study. Systemic chemotherapy alone was used in 71 eyes while chemotherapy plus laser was used in 20 eyes. Demographic characteristics of both groups were similar. Macular relapse rates were similar between groups: 22/71 (31%) eyes in chemotherapy group and 9/20 (45%) eyes in laser group (p=0.29). There was no increase in vitreous relapses in the laser group (2/20 eyes), compared with the chemotherapy group 10/71 eyes (p=0.99). Survival analysis demonstrated similar time to first relapse between groups. Final visual acuity was equal between groups with 6/15 or better present in 31.1% of eyes in the chemotherapy group and 37.5% of eyes in the laser group (p=0.76). Presence of tumour at the fovea was predictive of final visual acuity, regardless of treatment group., Conclusion: Adjuvant laser in the treatment of retinoblastoma is safe and does not lead to increased rate of vitreous recurrence. Final visual acuity is determined by the presence of tumour at the fovea and not the use of laser., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

This study aimed to genetically and clinically characterize a unique cohort of 25 individuals from 21 unrelated families with autosomal recessive nanophthalmos (NNO) and posterior microphthalmia (MCOP) from different ethnicities. An ophthalmological assessment in all families was followed by targeted MFRP and PRSS56 testing in 20 families and whole-genome sequencing in one family. Three families underwent homozygosity mapping using SNP arrays. Eight distinct MFRP mutations were found in 10/21 families (47.6%), five of which are novel including a deletion spanning the 5' untranslated region and the first coding part of exon 1. Most cases harbored homozygous mutations (8/10), while a compound heterozygous and a monoallelic genotype were identified in the remaining ones (2/10). Six distinct PRSS56 mutations were found in 9/21 (42.9%) families, three of which are novel. Similarly, homozygous mutations were found in all but one, leaving 2/21 families (9.5%) without a molecular diagnosis. Clinically, all patients had reduced visual acuity, hyperopia, short axial length and crowded optic discs. Retinitis pigmentosa was observed in 5/10 (50%) of the MFRP group, papillomacular folds in 12/19 (63.2%) of MCOP and in 3/6 (50%) of NNO cases. A considerable phenotypic variability was observed, with no clear genotype-phenotype correlations. Overall, our study represents the largest NNO and MCOP cohort reported to date and provides a genetic diagnosis in 19/21 families (90.5%), including the first MFRP genomic rearrangement, offering opportunities for gene-based therapies in MFRP-associated disease. Finally, our study underscores the importance of sequence and copy number analysis of the MFRP and PRSS56 genes in MCOP and NNO.

Retinoblastoma is the most common eye malignancy in childhood caused by mutations in the RB1 gene. Both alleles of the RB1 gene must be mutated for tumour development. The initial RB1 mutation may be constitutional germline or somatic (originating in one retinal cell only). Distinguishing between these alternative mechanisms is crucial, with wider implications for management of the patient and family members. Bilateral retinoblastoma is nearly always due to a constitutional mutation; however, approximately 15% of unilateral cases also carry a germline mutation, and identifying these cases is important. This can be achieved by identifying both mutation types in tumour tissue and excluding their presence in blood. Modern eye-saving chemotherapy treatment (systemic, intra-arterial and intravitreal) has resulted in fewer enucleations. As a result, tumour tissue required to identify sporadic RB1 mutation(s) is not always available. Modern intravitreal chemotherapeutic techniques for retinoblastoma involve aspiration of aqueous humour (AH), providing a novel sample source for analysis. By analysing cell-free DNA present in the AH fluid of eyes affected with retinoblastoma, we have developed a screening test capable of detecting somatic RB1 mutations that is comparable to current tests on enucleated tumour tissue. The results obtained with fluid from enucleated eyes were concordant with tumour tissue in all 10 cases analysed. In addition, AH analysis from two patients undergoing intravitreal chemotherapy successfully identified somatic variants in both cases. Our findings suggest that AH fluid is a promising source of tumour-derived DNA in retinoblastoma for analysis., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY. Published by BMJ.)

Background: Children with treated retinoblastoma undergo frequent examinations to monitor for recurrent or new tumours. Examinations under anaesthesia allow a more complete examination in younger children, however they are stressful for the family, subject the child to medical risk and consume resources. The risk of recurrent or new tumours declines with age and it is common practice to examine older children without general anaesthesia. There are no studies on the safety and cost effectiveness of this practice, or guidelines on when examination without anaesthesia (EWA) can be safely commenced., Procedure: Retrospective case note review of 128 sequential patients treated for retinoblastoma in a national referral centre over 10 years., Results: Following exclusions, 113 eyes of 84 children were analysed. The mean age at diagnosis was 20 months (range birth to 71 months). There were 55 unilateral and 29 bilateral cases. The mean follow-up was 77.7 months (range 12-178 months). EWA was commenced at a mean age of 53 months (range 12-98 months). The age of conversion to EWA was largely dependent on child cooperation and disease activity. Tumour activity was detected on EWA in one child at the age of 86 months, 9 months after the last active treatment and treated successfully., Conclusions: Examination without general anaesthesia does not appear to expose children to an increased risk of undetected tumour growth. This study highlights the important factors to be considered when deciding a safe time to commence EWA., (© 2013 Wiley Periodicals, Inc.)

Warburg Micro syndrome and Martsolf syndrome are heterogenous autosomal-recessive developmental disorders characterized by brain, eye, and endocrine abnormalities. Previously, identification of mutations in RAB3GAP1 and RAB3GAP2 in both these syndromes implicated dysregulation of the RAB3 cycle (which controls calcium-mediated exocytosis of neurotransmitters and hormones) in disease pathogenesis. RAB3GAP1 and RAB3GAP2 encode the catalytic and noncatalytic subunits of the hetrodimeric enzyme RAB3GAP (RAB3GTPase-activating protein), a key regulator of the RAB3 cycle. We performed autozygosity mapping in five consanguineous families without RAB3GAP1/2 mutations and identified loss-of-function mutations in RAB18. A c.71T > A (p.Leu24Gln) founder mutation was identified in four Pakistani families, and a homozygous exon 2 deletion (predicted to result in a frameshift) was found in the fifth family. A single family whose members were compound heterozygotes for an anti-termination mutation of the stop codon c.619T > C (p.X207QextX20) and an inframe arginine deletion c.277_279 del (p.Arg93 del) were identified after direct gene sequencing and multiplex ligation-dependent probe amplification (MLPA) of a further 58 families. Nucleotide binding assays for RAB18(Leu24Gln) and RAB18(Arg93del) showed that these mutant proteins were functionally null in that they were unable to bind guanine. The clinical features of Warburg Micro syndrome patients with RAB3GAP1 or RAB3GAP2 mutations and RAB18 mutations are indistinguishable, although the role of RAB18 in trafficking is still emerging, and it has not been linked previously to the RAB3 pathway. Knockdown of rab18 in zebrafish suggests that it might have a conserved developmental role. Our findings imply that RAB18 has a critical role in human brain and eye development and neurodegeneration., (Copyright © 2011 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.)

Purpose: Most infantile periocular hemangiomas undergo rapid growth in the first year of life, followed by gradual resolution over years. Treatment is indicated if vision is compromised and is usually continued through the growth phase. The objective of this study was to determine which clinical characteristics might aid in the prediction of growth and/or regression patterns of periocular hemangiomas., Methods: Retrospective review of medical records and photographs of children with periocular hemangiomas presenting to a UK pediatric eye unit over a 7-year period. Age at presentation, growth pattern, size, location, amblyopia, and refractive status were documented., Results: Forty-two infants with periocular hemangiomas were evaluated between 2000 and 2007, with a mean follow-up of 24 months (range, 6 months to 5 years). One-third (n=14, 33%) of the hemangiomas were superficial (strawberry nevi); one-third were subcutaneous (n=13, 31%), and the remainder were mixed (n=8, 19%) and orbital (n=7, 17%). There was a marked difference between the growth patterns of superficial (strawberry nevi) and deeper hemangiomas (orbital and subcutaneous), with a more prolonged period of growth noted in the deeper hemangiomas., Conclusions: Periocular hemangiomas with a deep component tend to have a later onset and prolonged period of growth compared to strawberry nevi. Clinically evident depth of the hemangioma appears to be a valuable predictor of rapidity of resolution. This finding may be useful in assessing prognosis and planning treatment of infantile periocular hemangiomas.

Knobloch syndrome (KNO) is a rare autosomal recessive condition caused by pathogenic mutations in the COL18A1 gene. It is characterized by high myopia, vitreoretinal degeneration, retinal detachment and midline encephalocoele or midline occipital bone defect. We report a case of KNO confirmed by direct sequence analysis of the COL18A1 gene with typical ocular features, and previously unreported systemic features: occipital hair tuft with transient CSF leak and bilateral renal abnormalities. This case illustrates a new phenotypic variant of this syndrome.

Purpose: To report clinical and genetic findings in a white British family with autosomal recessive cornea plana (CNA2) with a negative history for consanguinity. To look for evidence of a common ancestry with previously reported Finnish CNA2 patients by studying haplotypes., Methods: Clinical examination and direct sequencing of the keratocan (KERA) gene was performed in two siblings affected with CNA2 and one unaffected parent. We also studied 22 single nucleotide polymorphisms distributed in the KERA genomic region by direct sequencing in this family as well as in one additional Finnish patient with CNA2 and 24 white British control subjects., Results: Both siblings had the homozygous c.740A>G mutation leading to a p.N247S amino acid change originally reported as the founder mutation in 35 Finnish families. Genetic characterization of genomic regions surrounding the gene revealed large linkage disequilibrium, but the presence of shared extended haplotypes between affected individuals from Finland and the United Kingdom is consistent with a recent common ancestor., Conclusions: This is the first description of recessive cornea plana in a white British family and it is the second report on the p.N247S change in the KERA gene. Extended haplotype analysis suggests that the two geographically remote occurrences of the c.740A>G mutation may have a common origin.

We report a case of megacystis-microcolon-intestinal hypoperistalsis syndrome (MMIHS), occurring in association with mydriasis, in a female infant born to consanguineous Asian parents. This association has not previously been reported and is of interest because mydriasis has been found in a murine MMIHS model produced by knockout of the genes coding for the alpha3 subunit or the beta2 and beta4 subunits of the neuronal nicotinic acetylcholine receptor. This may provide an important clue to the genetic basis of MMIHS in humans.

Purpose: To report 14 cases (28 eyes) of cataract associated with type-1 diabetes mellitus in young children and adolescents., Methods: Retrospective review of the medical records of 14 patients from seven institutions. All patients under the age of 18 years who met the inclusion criteria of type-1 diabetes mellitus and cataract were included., Results: Mean age at the time of diabetes diagnosis was 9.8 years (range, 0.5-14 years), and mean age at cataract diagnosis was 11.7 years (range, 5-16 years). Two patients presented with cataracts one month before the diagnosis of diabetes; seven after the diagnosis of diabetes; and in five patients the cataract was found at the time the diabetes was diagnosed by the pediatrician. Nineteen out of 23 operated eyes had a best corrected post operative visual acuity of 20/40 or better. Two patients (4 eyes) developed diabetic retinopathy postoperatively., Conclusions: Although cataract formation in type-1 diabetes is rare, it is treatable and potentially sight-saving in young children and adolescents.

Background: Screening is necessary for infants at risk of retinopathy of prematurity. Despite local anaesthetic drops, infants find eye examinations distressing, displaying behavioural and physiological changes indicating acute pain. Oral sucrose and non-nutritive sucking reduce pain responses associated with invasive procedures., Objective: To evaluate the use of oral sucrose and/or pacifier for reducing pain responses during eye examinations., Methods: Forty infants <32 weeks gestation or <1500 g birth weight, in two neonatal units, were randomised to one of four interventions administered two minutes before their first screening examination: 1 ml sterile water as placebo (group 1, n = 10), 1 ml 33% sucrose solution (group 2, n = 10), 1 ml sterile water with pacifier (group 3, n = 9), or 1 ml 33% sucrose solution with pacifier (group 4, n = 11). Examinations were videotaped. Two observers, blind to the intervention, assessed recordings. Pain responses were scored using the premature infant pain profile (PIPP)., Results: The groups were similar in gestation, birth weight, and age at examination. Mean PIPP scores were 15.3, 14.3, 12.3, and 12.1 for groups 1, 2, 3, and 4 respectively. Analysis of variance showed a significant difference in PIPP score between groups (p = 0.023). Infants randomised to pacifiers scored lower than those without pacifiers (p = 0.003). There was no difference between groups receiving sucrose and those receiving water (p = 0.321)., Conclusions: Non-nutritive sucking reduced distress responses in infants undergoing screening for retinopathy of prematurity. The difference in response was large enough to be detected by a validated assessment tool. No synergistic effect of sucrose and pacifier was apparent in this group.

Hermansky-Pudlak syndrome (HPS) is genetically heterogeneous, and mutations in seven genes have been reported to cause HPS. Autozygosity mapping studies were undertaken in a large consanguineous family with HPS. Affected individuals displayed features of incomplete oculocutaneous albinism and platelet dysfunction. Skin biopsy demonstrated abnormal aggregates of melanosomes within basal epidermal keratinocytes. A homozygous germline frameshift mutation in BLOC1S3 (p.Gln150ArgfsX75) was identified in all affected individuals. BLOC1S3 mutations have not been previously described in patients with HPS, but BLOC1S3 encodes a subunit of the biogenesis of lysosome-related organelles complex 1 (BLOC-1). Mutations in other BLOC-1 subunits have been associated with an HPS phenotype in humans and/or mouse, and a nonsense mutation in the murine orthologue of BLOC1S3 causes the reduced pigmentation (rp) model of HPS. Interestingly, eye pigment formation is reported to be normal in rp, but we found visual defects (nystagmus, iris transilluminancy, foveal hypoplasia, reduced visual acuity, and evidence of optic pathway misrouting) in affected individuals. These findings define a novel form of human HPS (HPS8) and extend genotype-phenotype correlations in HPS.

Aims: To document and discuss the long term outcome of a new ophthalmic treatment for laryngo-onycho-cutaneous (LOC) syndrome., Methods: Two children were treated by excision of ocular granulation tissue and ocular surface rehabilitation with frozen amniotic membrane (AM). The clinical course of both patients was followed and documented at 2 years and 4 years following the surgery., Results: Patient 1 demonstrated limited recurrence of granulation tissue at 10 months. After 36 months, re-growth of granulation and scar tissue required a further three subsequent operations to the right eye in an attempt to keep the optical axis clear. 4 years postoperatively, neither eye has a clear visual axis. In contrast similar surgery for the right eye of patient 2 has been highly successful, with only very limited non-progressive recurrence after 2 years of follow up. The operation to the left eye has been similarly effective although the follow up is only 6 months., Conclusions: Ocular surface rehabilitation with AM is the first partially effective treatment for the eye complications of LOC syndrome. The surprising benefit from AM may stem from the primary pathology of the condition. LOC syndrome is caused by a genetic defect resulting in an unusual N-terminal deletion of the alpha3a chain of the basement membrane protein laminin 5. One mechanism through which AM transplantation may act to reduce ocular scarring in this disease is to supplement the abnormal secreted laminin 5 with healthy transplanted laminin. Despite its initial efficacy one episode of AM treatment does not guarantee long term control of the scarring process and variations in AM graft efficacy may be related to other complicating factors such as limbal stem cell deficiency or severity of the initial scarring process.

Purpose: To test the incidence of mutations in RPGR ORF15 in six families with X-linked progressive retinal degeneration (cone-rod dystrophy [XLCORD], macular or cone dystrophy) and to undertake a detailed phenotypic assessment of families in whom ORF15 mutations were identified., Methods: To amplify and sequence ORF15 in its entirety, a cloning strategy was developed. Families with mutations in ORF15 underwent electrophysiological testing, color vision assessment, color fundus photography, and fundus autofluorescence (AF) imaging., Results: Novel protein truncation mutations were identified in two families. In family A, a 2-bp mutation was identified in ORF15+A1094C G1095T, predicted to result in a truncated protein (E364D/E365X). In family B, a G-to-T transversion (ORF15+1176G>T) resulted in a nonsense mutation (G392X). Characteristics of phenotype in both families included progressive deterioration of central vision and subsequently night vision, mild photophobia, and moderate to high myopia. Ophthalmoscopic abnormalities were generally confined to the macula. A parafoveal ring of increased AF was observed, and electrophysiological evidence of a greater generalized abnormality in cone than rod responses were consistent with a cone-rod dystrophy phenotype., Conclusions: The cloning strategy for ORF15 facilitated comprehensive sequence analysis in patients. Two families were identified with nonsense mutations, and clinical evaluation revealed them both to have a similar phenotype. The presence of a parafoveal ring of increased AF was an early indicator of affected status in these families. No disease-causing mutations in ORF15 were detected in four other families, suggesting that ORF15 mutations may not be the most common cause of XLCORD.

Warburg Micro syndrome (WARBM1) is a severe autosomal recessive disorder characterized by developmental abnormalities of the eye and central nervous system and by microgenitalia. We identified homozygous inactivating mutations in RAB3GAP, encoding RAB3 GTPase activating protein, a key regulator of the Rab3 pathway implicated in exocytic release of neurotransmitters and hormones, in 12 families with Micro syndrome. We hypothesize that the underlying pathogenesis of Micro syndrome is a failure of exocytic release of ocular and neurodevelopmental trophic factors.

Purpose: To determine the molecular basis for phenotypic variability in a three-generation consanguineous family containing a single individual with complete achromatopsia and three individuals with progressive cone dystrophy., Methods: Four affected individuals underwent ophthalmic examination, electrophysiological assessment, color fundus photography, and psychophysical testing. Blood samples were obtained for DNA extraction and mutation screening of the cone-specific cGMP-gated (CNG) channel protein gene CNGB3 was undertaken., Results: The clinical findings in one family member were consistent with a diagnosis of complete achromatopsia, with nystagmus, photophobia, and poor visual acuity from early infancy and complete color-blindness, normal fundi, and absent cone responses with normal rod responses on electroretinography (ERG). Mutation analysis revealed her to be homozygous for the common CNGB3 achromatopsia mutation, 1148delC (Thr383fs). In contrast, the three other symptomatic individuals in the family had findings consistent with progressive cone dystrophy. Their visual problems began later in childhood (ranging from 3 to 14 years of age) and there was evidence of progressive deterioration in cone function. All three had a marked tritanopic color vision defect and fundoscopy revealed bilateral macular atrophy. Electrophysiological testing of these three subjects demonstrated clear evidence of progressive deterioration of cone responses over time; rod responses were normal. All three individuals with this progressive phenotype were found to be compound heterozygotes for the 1148delC (Thr383fs) frameshift mutation and a novel Arg403Gln missense mutation in CNGB3., Conclusions: Mutations in CNGB3, which have been shown to cause achromatopsia, are now shown to be associated with autosomal recessive progressive cone dystrophy. In this study, a novel Arg403Gln mutation was identified, located in the middle of the pore domain of the cone CNG cation channel beta-subunit, which when associated with the nonsense mutation Thr383fs, resulted in progressive cone dystrophy.

Objective: To establish the prevalence among women of primary Sjögren's syndrome (PSS) in Birmingham, UK., Methods: Eight hundred and forty-six female Caucasians from two general practitioner lists were invited to complete a questionnaire that included a screening question on dry eyes and mouth. Individuals who responded positively were evaluated further., Results: Overall, 65/% of individuals who were sent a questionnaire responded. Two had possible PSS, but were negative for anti-Ro/La antibodies. Our estimates of the prevalence of PSS ranged from < 0.1% up to 0.4%, depending on the assumptions used., Conclusion: Our data support previous studies suggesting a prevalence of PSS in the community of 0.1-0.6% rather than those suggesting a higher figure.

Purpose: High myopia in childhood is associated with important ocular and systemic conditions. However in the UK, high myopia in early childhood is not specifically identified in current ophthalmology, optometry, or orthoptic protocols for screening, referral, or investigation. An ongoing study in the West Midlands, UK, is investigating high myopia presenting to community health care clinics with the aim of compiling guidelines for assessment and subsequent referral., Methods: Children with high myopia were identified from community optometric and orthoptic sources and invited for an ophthalmology and optometry examination to ascertain possible ocular or systemic disease., Results: High myopia with no associated ocular or systemic condition was present in 15 (56%) of the children. In seven children (25%), associated ocular problems were found including unrecognized retinal dystrophies and amblyopia. Systemic disorders associated with high myopia were found in five children (19%) and included Sticklers syndrome, Weill-Marchesani syndrome, and homocystinuria. In one child, the diagnosis made before this study was found to be incorrect, and in another child, the results were inconclusive. In two cases, the diagnosis of a systemic condition in the child led to the identification of the disease in at least one relative., Conclusions: There is a high prevalence of ocular and systemic abnormality in young children seen in the community. Optometric and ophthalmologic assessment of children less than 10 years with myopia > or =5 D is likely to identify significant ocular or systemic disease, a proportion of which will respond to medical intervention. Detection and prompt referral of these cases by community health care services may be expected to prolong vision and possibly life expectancy.

Four infants developed invasive Pseudomonas aeruginosa ophthalmic infections between 5 and 90 days of age. Three died from septicaemia, and the fourth required enucleation of one eye. Absent red reflexes or other eye signs in a septicaemic infant merit urgent ophthalmological assessment for endophthalmitis, in particular, Pseudomonas.

Objective: To date, Micro syndrome has been reported in only three children from one family. We describe an additional 14 children from 11 families., Design: Retrospective case series., Participants: Fourteen children from 11 families attending one of five British hospitals., Main Outcome Measures: The following features were documented: pre- and postoperative eye findings, electrophysiologic analysis, systemic abnormalities, development, neuroimaging, genealogy, geographic origin of family., Results: We expand and modify the description of ocular and electrophysiologic findings in Micro syndrome. The eye findings of microphakia, microphthalmos, characteristic lens opacity, and atonic pupils were the presenting feature in all infants and were the most reliable diagnostic signs in the immediate postnatal period. Cortical visual impairment, microcephaly, and developmental delay were not always detectable initially; they developed in all children by 6 months of age. Microgenitalia were a useful diagnostic clue in affected males only. Therefore, eye features were more consistently useful in determining diagnosis than dysmorphology or brain imaging. The families of all the children originate from the Muslim population of Northern Pakistan. Inheritance is likely to be autosomal recessive., Conclusions: Micro syndrome usually presents to the ophthalmologist, who may be able to make the diagnosis on the basis of characteristic eye findings combined with ethnic origin. Initially, the nature and severity of nonophthalmic features are not apparent. Early diagnosis of the underlying condition is important to guide management of the cataracts, glaucoma, and developmental delay. It is helpful for the family and medical staff to be aware of the low level of vision that develops despite optimal ophthalmic intervention. Genetic counseling extending into the wider family is particularly important in view of the high rate of consanguinity.

Purpose: High myopia in early childhood is a recognised association of ocular and systemic disease. The aim of this study was to describe the types, pattern and frequency of these associations., Methods: All children presenting to two ophthalmology units over 3 years who were found to have high myopia were recruited. High myopia was defined as one or both eyes demonstrating 6 dioptres spherical equivalent or more of myopic refractive error on retinoscopy. We limited the age to less than 10 years old. A retrospective case review was undertaken of the 112 consecutive children who fulfilled the criteria above. The demographic data, source and indication for referral were recorded along with the ocular and systemic findings and diagnosis., Results: Only 9 (8%) of the children had 'simple high myopia' with no associated ocular or systemic associations. In 54% there was an underlying systemic association with or without further ocular problems (e.g. developmental delay, prematurity, Marfan, Stickler, Noonan, Down syndrome) and in the remaining 38% there were further ocular problems associated with the high myopia (e.g. lens subluxation, coloboma, retinal dystrophy, anisometropic amblyopia). A family history of high myopia did not preclude associated abnormality: in 4 cases the diagnosis of a systemic condition in the child led to the identification of the disease in at least one myopic relative. Asian (p < 0.001) and male (p < 0.05) patients were overrepresented in the series., Conclusion: High myopia is strongly associated with systemic and ocular problems; it may be the reason for the child's initial medical referral and an important clue to an underlying systemic or ocular condition. Referrals infrequently originated from community optometrists despite prior attendance. We suggest that all children under 10 years of age with high myopia are referred to a paediatric ophthalmology clinic for review and we propose a structured clinical evaluation in the hospital eye clinic.

Purpose: We investigated whether disparity between visually evoked potential (VEP) acuity scores and Teller Acuity Card (TAC) scores varied according to presence of ocular or neurologic conditions., Methods: Charts from 175 children (mean age, 34.8 months; range, 3 to 158 months) referred for visual acuity testing were examined. All children had been tested with pattern-alternation VEP and TAC and had undergone a complete eye examination. VEP and TAC acuity scores were relative to age-expected acuity scores for each acuity test. The absence and degree of macular abnormality, retinal abnormality, optic nerve hypoplasia, optic nerve atrophy, cortical visual impairment, developmental delay, cerebral palsy, seizures, and nystagmus were noted. Analysis of variance models were used to determine whether differences between VEP and TAC scores varied according to the presence of specific deficits. Logistic regression analysis determined whether degree of specific deficits was associated with a greater chance of inconsistency between VEP and TAC scores (>0.3 log unit difference)., Results: Inconsistent scores were found in 48% of children. Developmental delay was associated with relatively poorer TAC than VEP score, and the chance of inconsistency increased with severity of developmental delay., Conclusions: Diagnosis-dependent variability exists between TAC and VEP scores. Therefore knowledge of the clinical picture is necessary in interpretation of VEP and TAC scores. It is not clear which test is more useful when a disparity exists, either from this or previous studies. When visual acuity is assessed longitudinally in a given child, then consistency in method for acuity assessment is important.

Background: This study was conceived to provide an insight into the spectrum of glaucoma in the pediatric population. We also set out to compare the success of disease control and the prognosis for vision within the different diagnostic subgroups. This is the largest single population of children with glaucoma that has been so described and compared., Methods: The charts of children who were first seen between birth and age 16 years and who attended the Hospital for Sick Children with any form of glaucoma between January 1974 and January 1995 were reviewed and entered into the study., Results: Data are presented for 306 children. Congenital glaucoma was the most common subtype, accounting for 38%. Patients with congenital glaucoma were young, had surgery, and had more operations than any other group except those with aniridia. Goniotomy offered a cure in 47.8% of the patients. A bimodal distribution reflected their visual performance. Patients with aphakic glaucoma, the next most prevalent group (20%), presented at an older age (4.5 years). Surgical intervention was performed in 50% of these children. Nearly all patients with Sturge-Weber syndrome (80%) had surgery. The following glaucoma groups were associated with a poor visual outcome: aniridia, anterior segment developmental anomalies involving the cornea, uveitis with glaucoma other than steroid induced, retinopathy of prematurity, and persistent hyperplastic primary vitreous. Steroid-induced glaucoma and anterior segment dysgenesis, excluding Peters anomaly, had uniformly good outcomes., Conclusion: The ability to control glaucoma in childhood and visual prognosis is highly variable. Particular diagnostic categories do consistently well and some do poorly.

Purpose: The purpose of the study was to compare the results of three techniques of cataract surgery in children. Two methods included intraocular lens (IOL) implantation and one used contact lens correction of aphakia., Design: Nonrandomized clinical trial., Participants: Seventy-seven eyes of 50 children between the ages of 2 1/2 and 16 years who had cataract surgery for the treatment of uncomplicated cataract., Intervention: Thirty-one eyes underwent a "conventional" style of implantation, and a "phaco-style" of surgery was used in 24 eyes. A contact lens was used as the primary means of aphakic correction in 22 eyes., Main Outcome Measures: The visual results and complications of each type of surgery were compared., Results: Corrected visual acuities did not differ significantly between the three groups 6 months after surgery. The incidence and type of complications were significantly different. Better lens centration, less long-term iris changes, or wound-related problems were observed with "phaco-style" modification of the technique of IOL insertion., Conclusions: Pediatric IOL insertion eliminated the need for contact lens wear and did not lead to a significantly different corrected visual acuity 6 months after surgery compared with lensectomy with contact lens correction. Adoption of some of the techniques of modern small-incision cataract surgery for pediatric IOL procedures produces a significant reduction in postoperative anterior segment complications compared with a standard limbal approach. Such modifications allow pediatric IOL insertion to be a safe alternative for the correction of pediatric aphakia.

The 5' splice site signal (5'ss) in Moloney murine sarcoma virus ts110 (MuSVts110) RNA was found to participate in the regulation of its splicing phenotype. This 5'ss (CAG/GUAGGA) departs from the mammalian consensus (CAG/GURAGU) at positions +4 and +6, both of which base pair with U1 and U6 small nuclear RNAs during splicing. A doubling in splicing efficiency and near elimination of the splicing thermosensitivity characteristic of MuSVts110 were observed in 5'ss mutants containing a U at position +6 (termed 5' A6U), even in those in which U1-5'ss complementarity had been reduced. At the permissive temperature (28 degrees C), the 5' A6U mutation increased the efficiency of the second splicing reaction, while at the nonpermissive temperature (39 degrees C), both splicing reactions were positively affected.

Purpose: To determine long-term changes in duration of relief with serial treatments of botulinum A toxin (BAT) used to treat benign essential blepharospasm and hemifacial spasm, in view of conflicting reports as to whether BAT has an increasing, decreasing, or an unchanging duration of effect over a long period of treatment., Methods: Thirty-two patients with facial dyskinesia (20 with essential blepharospasm, 12 with hemifacial spasm) were followed between 5 and 9 years through a mean of 18 (range, 12-32) BAT treatments with prospective documentation of intervals of relief from symptoms. Repeated measures and linear regression analyses were used to determine trends in each group., Results: Marked inter- and intrapatient variability was found in the length of effect of BAT. Statistical analysis showed no significant changes in mean duration of relief within each group (P = 0.65 for essential blepharospasm, 0.36 for hemifacial spasm). There was a trend to slow decline in the interval of relief, especially in patients with an initial duration of effect greater than 150 days. No relation was found between duration of relief and age or sex of patient or grade and duration of disease before initial treatment., Conclusion: In the long term, the mean duration of relief from symptoms with BAT changes little over a period of serial treatments. Short-term fluctuations in the length of therapeutic effect did not indicate the development of a resistance to treatment.

Osteopetrosis should be considered in an infant with unexplained visual loss. In particular, the possibility of this diagnosis must be intimated to the radiologist involved in the investigation of the child.

We have cloned Moloney murine sarcoma virus (MuSV) MuSVts110 DNA by assembly of polymerase chain reaction (PCR)-amplified segments of integrated viral DNA from infected NRK cells (6m2 cells) and determined its complete sequence. Previously, by direct sequencing of MuSVts110 RNA transcribed in 6m2 cells, we established that the thermosensitive RNA splicing phenotype uniquely characteristic of MuSVts110 results from a deletion of 1,487 nucleotides of progenitor MuSV-124 sequences. As anticipated, the sequence obtained in this study contained precisely this same deletion. In addition, several other unexpected sequence differences were found between MuSVts110 and MuSV-124. For example, in the noncoding region upstream of the gag gene, MuSVts110 DNA contained a 52-nucleotide tract typical of murine leukemia virus rather than MuSV-124, suggesting that MuSVts110 originated as a MuSV-helper murine leukemia virus recombinant during reverse transcription rather than from a straightforward deletion within MuSV-124. In addition, both MuSVts110 long terminal repeats contained head-to-tail duplications of eight nucleotides in the U3 region. Finally, seven single-nucleotide substitutions were found scattered throughout MuSVts110 DNA. Three of the nucleotide substitutions were in the gag gene, resulting in one coding change in p15 and one in p30. All of the remaining nucleotide changes were found in the noncoding region between the 5' long terminal repeat and the gag gene. In NIH 3T3 cells transfected with the cloned MuSVts110 DNA, the pattern of viral RNA expression conformed with that observed in cells infected with authentic MuSVts110 virus in that viral RNA splicing was 30 to 40% efficient at growth temperatures between 28 and 33 degrees C but reduced to trace levels above 37 degrees C.

All patients referred for orbital imaging to the neuroradiology department of the Institute of Neurological Sciences in Glasgow over a three year period were enrolled in the study and were scheduled to undergo both magnetic resonance imaging and computed tomography. A total of 101 of the 110 referred patients were deemed suitable for analysis. Details of key presenting symptoms, signs, and a pre-imaging diagnosis were recorded prospectively. A final diagnosis was obtained by histology in 65% of cases with an orbital abnormality, by a minimum of one year of clinical review in 19.5%, by response to antibiotic or steroid therapy in 8.5%, or by conclusive investigations such as carotid angiography in in 7% of patients, 29% of the patients had no detectable orbital disease despite a minimum one years' follow-up, and so were regarded as a "normal" group. The images were interpreted prospectively by separate masked observers. The diagnostic accuracies of the two techniques were compared to the final diagnosis. The two imaging methods were shown to be comparable in overall diagnostic accuracy, with a small and statistically non-significant advantage held by magnetic resonance imaging. Interpretation of the two investigations gave more accurate information in different types of disease.

We describe a multisystem disease that affects children of Muslim families originating in the Punjab region of Pakistan and India. An altered cry due to vocal cord thickening, skin ulceration, nail abnormalities, and conjunctival scarring appear in the first few months of life. Progression and spread of the disease in these sites may be accompanied by involvement of other epithelial surfaces. The teeth may exhibit defective enamel formation. Histology reveals the formation of simple granulation tissue arising in the dermis and submucosa which become massively thickened and ulcerated. There is good evidence for an autosomal recessive gene defect, but the actual mechanism of the disease is not known. Medical and surgical therapy have been ineffective in altering the course of this devastating and usually fatal condition. We suggest the term LOGIC (laryngeal and ocular granulation tissue in children from the Indian subcontinent) for this newly established disease.