Homozygous mutations in PXDN cause congenital cataract, corneal opacity, and developmental glaucoma.

Anterior segment dysgenesis describes a group of heterogeneous developmental disorders that affect the anterior chamber of the eye and are associated with an increased risk of glaucoma. Here, we report homozygous mutations in peroxidasin (PXDN) in two consanguineous Pakistani families with congenital cataract-microcornea with mild to moderate corneal opacity and in a consanguineous Cambodian family with developmental glaucoma and severe corneal opacification. These results highlight the diverse ocular phenotypes caused by PXDN mutations, which are likely due to differences in genetic background and environmental factors. Peroxidasin is an extracellular matrix-associated protein with peroxidase catalytic activity, and we confirmed localization of the protein to the cornea and lens epithelial layers. Our findings imply that peroxidasin is essential for normal development of the anterior chamber of the eye, where it may have a structural role in supporting cornea and lens architecture as well as an enzymatic role as an antioxidant enzyme in protecting the lens, trabecular meshwork, and cornea against oxidative damage.

Ophthalmic findings in Apert's syndrome after craniofacial surgery: twenty-nine years' experience.

PURPOSE: To survey the spectrum of ophthalmic morbidity in Apert's syndrome after craniofacial surgery. DESIGN: A retrospective study of patients with Apert's syndrome managed at the Australian Craniofacial Unit from 1975 to 2004. PARTICIPANTS: Sixty-one patients (31 females and 30 males) had final ophthalmic reviews at a mean age of 9.3 years (standard deviation, 9.2; range, 0.2-48.3; median, 8.2 years). METHODS: Patients were identified from the unit database, and case notes were reviewed. Cases that had < or =2 recorded variables were excluded. Demographic details, age at last ophthalmic review, and total craniofacial operations performed were documented. MAIN OUTCOME MEASURES: Best-corrected visual acuity, cycloplegic refractions, strabismus, amblyopia, corneal abnormality, fundoscopic findings, and visually evoked potentials. RESULTS: The average number of craniofacial operations performed was 2 (range, 1-4; median, 2). Visual impairment was found in 54% of patients in at least one eye and in 19% of patients in their better eye. The most common cause was amblyopia, with a prevalence of 35%. Optic atrophy caused visual impairment in 5% of patients and corneal scarring in 8%. Sixty-three percent of patients had strabismus with more esotropia than exotropia. Ametropia was found in 69% of patients (42% were hypermetropic and 27% were myopic). Anisometropia of > or =0.75 diopters was present in 16 cases (50%). CONCLUSIONS: Visual impairment is a common finding in Apert's syndrome and amblyopia is the major cause. Ametropia, astigmatism, anisometropia, and strabismus frequently occur in patients with Apert's syndrome at final ophthalmic review. Although optic atrophy was the major cause of visual loss in the era prior to craniofacial surgery, the prevalence of optic atrophy is low since the adoption of current surgical protocols. Corneal damage also contributed toward visual impairment. Early detection and adequate management of amblyopia, timely decompressive surgery before the presence of optic atrophy, and protection of the cornea should be the management goals of ophthalmologists in craniofacial units managing these patients.

Ophthalmic findings in apert syndrome prior to craniofacial surgery.

PURPOSE: To determine ophthalmic findings in patients with Apert syndrome before craniofacial surgery. DESIGN: A cross-sectional retrospective study. METHODS: Review of 63 cases (27 males, 36 females) with Apert syndrome without craniofacial surgery from the Australian Craniofacial Unit. Demographic data, age of presentation, and ophthalmic findings at the first presentation were recorded. RESULTS: At a mean age of four years and median age of one year, at least 14% of patients had amblyopia, 60% of patients had strabismus, 19% of patients had anisometropia, and 34% of eyes had ametropia. Exposure keratopathy and corneal scarring occurred in at least 13% of patients and optic atrophy in at least 8% of patients. CONCLUSIONS: This study demonstrated that patients with Apert syndrome were at risk of amblyopia because of high prevalence of refractive errors, strabismus, and anisometropia. Exposure keratopathy and corneal scarring occurred commonly.

The ophthalmic sequelae of Pfeiffer syndrome and the long-term visual outcomes after craniofacial surgery.

BACKGROUND: Pfeiffer syndrome is a rare, genetic condition characterized by craniosynostosis and midface hypoplasia, with resultant ophthalmic sequelae. The gold standard of treatment is fronto-orbital advancement. We analyzed a large database of Pfeiffer syndrome patients to report the rate of ophthalmic sequelae and the long-term visual outcomes after craniofacial surgery and to compare Pfeiffer syndrome to other craniosynostosis syndromes. METHODS: The medical records of Pfeiffer syndrome patients examined between 1988 and 2010 were examined retrospectively. Diagnosis was based on clinical and genetic testing. Long-term data were presented as a rate of incidence per person-year to overcome variable follow-up times. RESULTS: A total of 22 patients were included. Proptosis (n = 21 [95%]), refractive error (n = 13 [59%]), and strabismus (n = 12 [55%]) were the most common primary features at presentation. Exposure keratitis (n = 9 [41%]) and amblyopia (n = 3 [14%]) were the most common secondary features. At presentation, 24 eyes [86%] with documented best-corrected visual acuity were normal; 4 [14%] were impaired; and none were blind. Fronto-orbital advancement reduced the rate of proptosis from 28%/person-year at presentation to 2%/person-year. There were no cases of active exposure disease postoperatively. At last follow-up, there was a 7%/person-year rate of impaired vision secondary to corneal scarring and amblyopia and a 3%/person-year rate of blindness-all from optic atrophy. CONCLUSIONS: In this study, the rates of proptosis and exposure keratitis were high in Pfeiffer syndrome, especially compared to Apert and Crouzon syndromes. Fronto-orbital advancement was successful in correcting orbital abnormalities. Long-term ophthalmic follow-up is essential to ensure best visual outcome.

Juvenile arthritis-associated uveitis: visual outcomes and prognosis.

BACKGROUND: The current issues in the management of uveitis associated with juvenile arthritis revolve mainly around the treatment of mild disease and how to treat patients with more severe disease. The aims of this study were to determine the incidence of uveitis in a cohort of patients with juvenile arthritis as well as the nature of treatment and the risk factors for visual loss. METHODS: Review of the charts of 71 patients with juvenile arthritis, as defined by the American Academy of Rheumatology, seen between 1992 and 2001 at a combined rheumatology and ophthalmology clinic. Information collected included the patient's sex, age at diagnosis of arthritis and uveitis, and date of diagnosis of arthritis and uveitis. The rheumatologic diagnosis, results of serologic testing, and details of systemic and topical treatments were also recorded. RESULTS: There were 47 girls and 24 boys ranging in age from 16 months to 13 years. The median age at diagnosis of juvenile arthritis was 4 years and 1 month. Twenty-seven patients (38%) had uveitis. The median age at uveitis onset was 5.9 years, with an average interval of 18 months from the diagnosis of arthritis; 11 patients had uveitis at the time of arthritis diagnosis. There was a positive relation between anti-nuclear antibody positivity and the development of uveitis (p < 0.05). Thirteen (48%) of the 27 patients with uveitis had mild anterior segment inflammation, with fewer than 25 cells in the anterior chamber. This group had spontaneous resolution of uveitis without topical therapy. All the patients without uveitis had a final visual acuity of 6/9 or better. Five of the patients with uveitis had a final visual acuity of 6/36 or worse. Cataract was the most common complication affecting visual outcome. Cataract extraction initially improved the visual acuity, but posterior segment complications and glaucoma compromised the final visual outcome. INTERPRETATION: We found an incidence of uveitis of 38% with long-term follow-up of patients with juvenile arthritis; the uveitis was diagnosed an average of 18 months after the arthritis. Almost half of the patients with uveitis had minor anterior segment inflammation. These patients did not receive topical treatment and had good visual outcomes. Patients with uveitis at the time of diagnosis of arthritis tended to have a worse visual prognosis and experienced persistent uveitis despite treatment. In this series, cataract extraction was beneficial in improving visual acuity immediately postoperatively, but posterior segment changes and glaucoma may compromise final visual outcomes.

A survey of severe visual impairment and blindness in children attending thirteen schools for the blind in sri lanka.

PURPOSE: To identify the causes of blindness and severe visual impairment (BL/SVI) in children attending schools for the blind in Sri Lanka, and to provide optical devices and ophthalmic treatment where indicated. METHODS: Two hundred and six children under 16 years from 13 schools for the blind in Sri Lanka were examined by a team of ophthalmologists and optometrists. Data were entered in the World Health Organization Prevention of Blindness Eye Examination Record for Childhood Blindness (WHO/PBL ERCB). RESULTS: Of the 206 children, 83.5% were blind (BL = Visual acuity [VA] <3/60), and 9.2% had severe visual impairment (SVI = VA <6/60 to 3/60 in the better eye). The major anatomical site of BL/SVI was the retina in 35.9% of cases, followed by the whole globe in 22.4% of cases. The major underlying aetiologies of BL/SVI were unknown in 43.8% of cases and hereditary in 37.5%. Avoidable causes of BL/SVI accounted for 34.9% of cases; retinopathy of prematurity made up the largest proportion of this subgroup. One third of the children required an optical device to improve their vision. CONCLUSION: Just over one third of the children in schools for the blind in Sri Lanka had potentially avoidable causes of BL/SVI. Vision could also be improved in a third of children. The data support the need to develop specialized pediatric ophthalmic services, particularly in the face of advancing neonatal life support in Sri Lanka, and the need for increased provision of optical support.

A survey of visual impairment and blindness in children attending four schools for the blind in Cambodia.

PURPOSE: To identify the causes of blindness and severe visual impairment (BL/SVI) in children attending four schools for the blind in Cambodia and to provide spectacles, low vision aids, orientation and mobility training and ophthalmic treatment. METHODS: Children < 16 years of age were recruited from all 4 schools for the blind in Cambodia. Causes of visual impairment and blindness were determined and categorized using World Health Organization methods. RESULTS: Of the 95 children examined, 54.7% were blind (BL) and 10.5% were severely visually impaired (SVI). The major anatomical site of BL/SVI was the lens in 27.4%, cornea in 25.8%, retina in 21% and whole globe in 17.7%. The major underlying etiologies of BL/SVI were hereditary factors (mainly cataract and retinal dystrophies) in 45.2%, undetermined/unknown (mainly microphthalmia and anterior segment dysgenesis) in 38.7% and childhood factors in 11.3%. Avoidable causes of BL/SVI accounted for 50% of the cases; 12.9% of the total were preventable with measles being the commonest cause (8.1% of the total); 37.1% were treatable with cataracts and glaucoma being the commonest causes (22.6% and 4.8% respectively). More than 35% of children required an optical device and 27.4% had potential for visual improvement with intervention. CONCLUSION: Half of the BL/SVI causes were potentially avoidable. The data support the need for increased coverage of measles immunization. There is also a need to develop specialized pediatric ophthalmic services for the management of surgically remediable conditions, to provide optometric, low vision and orientation and mobility services. Genetic risk counseling services also may be considered.

A survey of visual impairment and blindness in children attending seven schools for the blind in Myanmar.

PURPOSE: To determine the causes of visual impairment and blindness amongst children in schools for the blind in Myanmar; to identify the avoidable causes of visual impairment and blindness; and to provide spectacles, low vision aids, orientation and mobility training and ophthalmic treatment where indicated. METHODS: Two hundred and eight children under 16 years of age from all 7 schools for the blind in Myanmar were examined and the data entered into the World Health Organization Prevention of Blindness Examination Record for Childhood Blindness (WHO/PBL ERCB). RESULTS: One hundred and ninety nine children (95.7%) were blind (BL = Visual Acuity [VA] < 3/60 in the better eye) and 3 had severe visual impairment (SVI = VA < 6/60 to 3/60 in the better eye). Most children had corneal abnormalities as the major anatomical site of SVI/BL (100, 49.5%), however the cause of SVI/BL was unknown in the majority (88, 43.6%). Measles keratitis was the commonest identifiable cause (17.4%) and 88 children had avoidable causes of SVI/BL (43.6%). Nearly 16% of children required an optical device and 24.2% required medical attention, with a potential for visual improvement through intervention in 15.8%. CONCLUSION: Nearly half of the children in schools for the blind in Myanmar had potentially avoidable causes of SVI/BL. With measles being both the commonest identifiable and commonest avoidable cause, the data supports the need for a measles immunization campaign. There is also a need for a dedicated pediatric eye care center with regular ophthalmology visits to the schools, and improved optometric, low vision and orientation and mobility services in Myanmar.

Differential effects of FGFR2 mutation in ophthalmic findings in Apert syndrome.

Apert syndrome is mostly caused by one of the two specific point mutations in the fibroblast growth factor receptor 2 (FGFR2). The objective of this study was to determine whether there were any differences in the prevalence of ophthalmic features in Apert syndrome when comparing the Ser252Trp and Pro253Arg mutations in FGFR2. This was a retrospective study of patients with Apert syndrome with genotype analysis. The prevalence of five ophthalmic features, visual impairment, amblyopia, strabismus, corneal abnormality, and pale optic discs, were compared between the two FGFR2 genotypes. There were 25 (74%) cases with Ser252Trp mutation, and 9 (26%) cases with the Pro253Arg mutation in FGFR2. Ophthalmic findings in 20 cases of FGFR2 Ser252Trp and 9 cases of Pro253Arg mutation were compared. Visual acuity worse than 6/12 in at least one eye was present in 60% patients with FGFR2 Ser252Trp mutation compared with 12.5% patients with Pro253Arg mutation (P < 0.05). Forty percent of eyes with FGFR2 Ser252Trp mutation compared with 12.5% eyes with Pro253Arg mutation were worse than 6/12. There was a trend of more frequent amblyopia and strabismus in FGFR2 Ser252Trp mutation and more frequent optic disc pallor in the FGFR2 Pro253Arg mutation. There was a differential effect of FGFR2 mutations in ophthalmic findings in patients with Apert syndrome, with significantly greater prevalence of visual impairment in the Ser252Trp mutation compared with the Pro253Arg mutation. Further study would elucidate whether the trends in differential effects between the two mutations in amblyopia, strabismus, and optic disc pallor represent real differences.