Congenital Glaucoma: a Novel Ocular Manifestation of Hajdu-Cheney Syndrome.

Hajdu-Cheney Syndrome (HSC) is a rare multisystem disease in which the phenotype involves acro-osteolysis, severe osteoporosis, short stature, wormian bones, facial dysmorphism, central neurological abnormalities, cardiovascular defects, and polycystic kidneys. We describe an infant with severe manifestations of HCS in whom congenital glaucoma was a significant early feature, which has not been reported to date. HCS cases reported to date have involved truncating mutations in exon 34 of NOTCH2 upstream the PEST domain that lead to the development of a truncated and stable NOTCH2 protein which upregluates notch signaling. We describe a hitherto undescribed missense mutation that is predicted to be pathogenic, with functional characterization remaining to be performed. Serpentine fibula-polycystic kidney syndrome (SFPKS) is allelic to HCS and commonly associated with missense NOTCH2 mutations. Our patient provides new ophthalmological manifestations of HCS and provides insight into the potential role of notch signaling in the anterior chamber development.

An international comparison of retinopathy of prematurity grading performance within the Benefits of Oxygen Saturation Targeting II trials.

PurposeTo investigate whether the observed international differences in retinopathy of prematurity (ROP) treatment rates within the Benefits of Oxygen Saturation Targeting (BOOST) II trials might have been caused by international variation in ROP disease grading.MethodsGroups of BOOST II trial ophthalmologists in UK, Australia, and New Zealand (ANZ), and an international reference group (INT) used a web based system to grade a selection of RetCam images of ROP acquired during the BOOST II UK trial. Rates of decisions to treat, plus disease grading, ROP stage grading, ROP zone grading, inter-observer variation within groups and intra-observer variation within groups were measured.ResultsForty-two eye examinations were graded. UK ophthalmologists diagnosed treat-requiring ROP more frequently than ANZ ophthalmologists, 13.9 (3.49) compared to 9.4 (4.46) eye examinations, P=0.038. UK ophthalmologists diagnosed plus disease more frequently than ANZ ophthalmologists, 14.1 (6.23) compared to 8.5 (3.24) eye examinations, P=0.021. ANZ ophthalmologists diagnosed stage 2 ROP more frequently than UK ophthalmologists, 20.2 (5.8) compared to 12.7 (7.1) eye examinations, P=0.026. There were no other significant differences in the grading of ROP stage or zone. Inter-observer variation was higher within the UK group than within the ANZ group. Intra-observer variation was low in both groups.ConclusionsWe have found evidence of international variation in the diagnosis of treatment-requiring ROP. Improved standardisation of the diagnosis of treatment-requiring ROP is required. Measures might include improved training in the grading of ROP, using an international approach, and further development of ROP image analysis software.

Leber Hereditary Optic Neuropathy and Longitudinally Extensive Transverse Myelitis.

Leber Hereditary Optic Neuropathy is an inherited optic neuropathy caused by mitochondrial DNA point mutations leading to sudden, painless loss of vision. We report a case of an 8-year-old boy presenting with a radiological phenotype of longitudinally extensive transverse myelitis on a background of severe visual impairment secondary to Leber Hereditary Optic Neuropathy (LHON). He was found to have dual mitochondrial DNA mutations at 14484 (MTND6 gene) and 4160 (MTND1 gene) in a family with a severe form of LHON characterised by not only an unusually high penetrance of optic neuropathy, but also severe extra-ocular neurological complications. The m.14484T>C mutation is a common LHON mutation, but the m.4160T>C mutation is to our knowledge not reported outside this family and appears to drive the neurological manifestations. To our knowledge there have been no previous reports of spinal cord lesions in children with LHON.

Posterior to the ridge laser treatment for severe stage 3 retinopathy of prematurity.

BACKGROUND: Current methods of treating the avascular retina with laser photocoagulation for severe retinopathy of prematurity (ROP) are not completely effective in the reduction of visual morbidity. We report a case series in which additional laser treatment, called 'posterior laser', was delivered posterior to the neovascular ridge, for eyes with severe stage 3 ROP in zone II with avascular retina posterior to the ridge. DESIGN: Retrospective chart review. PARTICIPANTS: Infants who underwent laser treatment, posterior to the neovascular ridge for severe ROP at the Alberta Children's Hospital, between January 2005 and October 2008. METHODS: Charts were reviewed for 18 eyes of 11 patients and collected information included demographic data, clinical examination results, and digital retinal images. MAIN OUTCOME MEASURES: Structural and functional outcomes of treatment. RESULTS: Four (22%) of 18 eyes received 'posterior laser' as primary treatment and the remainder of eyes (78%) received 'posterior laser' following previous laser photocoagulation anterior to the neovascular ridge. Mean birthweight was 688 g (552-930) and mean gestational age was 24 weeks (23-28). There were no complications because of the posterior laser treatment. In all, 16 of 18 eyes experienced rapid regression of the ridge and subsequent decrease in vascular dilation and tortuosity within 1 week. Two eyes required vitrectomy for 4A retinal detachment; however, no eyes developed stage 4B ROP. CONCLUSION: Posterior to the ridge laser in the setting of the morphological criteria described had no increased safety concerns and resulted in rapid regression of ROP with good outcomes.

Visual acuity testability and comparability in Australian preschool children: the Sydney Paediatric Eye Disease Study.

PURPOSE: To establish standardised protocols for vision screening, testability and comparability of three different vision tests were examined in a population-based, cross-sectional sample of preschool children (Sydney Paediatric Eye Disease Study). METHODS: Measurement of presenting monocular distance visual acuity (VA) using the Amblyopia Treatment Study (ATS) HOTV protocol, was attempted by all (1774) children aged≥24 months. In addition, in children aged≥60 months (576), VA was also tested using the logMAR retro-illuminated HOTV or Early Treatment Diabetic Retinopathy Study (ETDRS) linear charts (CSV 1000). Children able to have both eyes tested monocularly were considered. RESULTS: Testability significantly increased with age for all VA tests. The ATS HOTV with an overall testability of 80% (females: 82%, males: 78%) was the most testable of the VA tests (P<0.0001). In children aged <3 years testability was low (≤47%) rising to≥80% in children aged≥3. In children≥60 months, testability was higher for the HOTV (94%) than the ETDRS (59%) chart. In those that did two VA tests, mean difference of the ATS HOTV compared with the HOTV(CSV) was -0.1, and compared with ETDRS was -0.12 (P<0.0001). CONCLUSIONS: Children aged <3 years had poor VA testability, whereas those 3 years and above were highly testable using the ATS HOTV. The HOTV (CSV) retro-illuminated test was appropriate for children aged >5 years, and may be possible in younger children with early educational exposure. When comparing VA measures using these tests, the higher VA attained using the ATS HOTV, needs to be taken into account.

Three horizontal muscle surgery for large-angle infantile esotropia: validation of a table of amounts of surgery.

PURPOSE: To validate a table of amounts of three horizontal muscle surgery in patients with large-angle infantile esotropia (≥60 prism dioptres, PD). METHODS: A prospective interventional case series reporting the postoperative alignment of 51 patients (27 male, 24 female) over a 15-year period was conducted. Surgery amounts were according to a published table developed on a previous patient cohort (n=49), using bilateral medial rectus recession with graded unilateral lateral rectus resection. Kaplan-Meier life-table survival curves were formulated for success to orthotropia (±10 PD) after one and subsequent horizontal muscle surgeries for up to 8 years follow-up. RESULTS: The median preoperative deviation was 65 PD (range 60-80 PD) and median age at surgery was 11.8 months (range 5.1 months-3.6 years). Surgical success to orthotropia (±10 PD) after one surgery was 100% at 2 months, 95.7% at 6 months, 91.3% at 12 months, 77.8% at 4 years, and 73.6% at 8 years. Postoperative failure requiring further horizontal surgery occurred in 17.6% (residual esotropia 4, consecutive exotropia 5). CONCLUSIONS: Our second cohort has reproduced the success rate of the previous cohort (77.8% vs 77.1% at 4 years). If the published table of surgical amounts is used, three horizontal muscle surgery in large-angle infantile esotropia (≥60 PD) appears to have a good long-term success rate, and does not lead to the high rates of either residual esotropia or consecutive exotropia reported by others in the literature.

Selective inner retinal dysfunction precedes ganglion cell loss in a mouse glaucoma model.

BACKGROUND/AIMS: To correlate ganglion cell function with defined parameters of the elevated intraocular pressure profile (IOP) in a mouse glaucoma model and to determine the temporal relationship of these functional changes with ganglion cell death. METHODS: Unilateral chronic ocular hypertension was induced in C57BL6/J mice by laser ablation of the limbal episcleral veins. Scotopic flash electroretinograms were recorded after 5, 10, 20, and 40 days to isolate specific outer and inner retinal responses. Inner retinal function was correlated with the pressure differential between treated and non-treated eyes at the time of electroretinographic recording, and with the cumulative IOP insult (the integral of the IOP.time profile). Peripheral and central ganglion cell densities were quantified by Brn-3 immunohistochemistry. RESULTS: Elevated IOP induced a preferential deficit in inner retinal function. The positive scotopic threshold response (pSTR) was suppressed by 68% on day 5, by 50% on day 10, by 54% on day 20 and by 46% on day 40 after laser treatment. Inhibition of the STR correlated with the pressure differential between treated and non-treated eyes but not with the IOP.time integral. Inner retinal dysfunction preceded the progressive death of ganglion cells. Ganglion cell loss occurred preferentially in peripheral retina and correlated with the cumulative IOP insult. CONCLUSION: We have demonstrated specific inner retinal dysfunction in an inducible mouse glaucoma model. STRs are sensitive to elevated IOP per se, and their early suppression reflects ganglion cell dysfunction rather than cell death. The correlation between IOP elevation and suppression of inner retinal function, in the context of the temporal progression of ganglion cell death, suggests that a portion of the IOP-mediated ganglion cell dysfunction may be reversible.

Telepaediatrics and diabetic retinopathy screening of young people with diabetes in Queensland.

We have examined the feasibility of a telemedicine-enabled screening service for children and adolescents with diabetes in Queensland. There are approximately 1400 young people with diabetes in Queensland and only about two-thirds of them are screened in accordance with international guidelines. A regional retinal screening service was established using a nonmydriatic digital retinal camera. Seven centres volunteered to participate in the study. During a five-month pilot trial, 83 of the young people with diabetes who attend these centres underwent digital retinal screening (3.7%). Retinal images were sent via email to a paediatric ophthalmologist for review and results were returned via email. A copy of each participant's results was forwarded by mail to the referring diabetes doctor and the participant and family. The majority of the image files (96%) were rated as excellent or good. Only one participant was identified as having an abnormal result. Participants and their families expressed satisfaction with the digital retinal screening process.

Proximal arterial vasoconstriction precedes regression of the hyaloid vasculature.

PURPOSE: To determine whether constriction of proximal arterial vessels precedes involution of the distal hyaloid vasculature in the mouse, under normal conditions, and whether this vasoconstriction is less pronounced when the distal hyaloid network persists, as it does in oxygen-induced retinopathy (OIR). METHODS: Photomicrographs of the vasa hyaloidea propria were analysed from pre-term pups (1-2 days prior to birth), and on Days 1-11 post-birth. The OIR model involved exposing pups to approximately 90% O(2) from D1-5, followed by return to ambient air. At sampling times pups were anaesthetised and perfused with india ink. Retinal flatmounts were also incubated with FITC-lectin (BS-1, G. simplicifolia,); this labels all vessels, allowing identification of vessels not patent to the perfusate. RESULTS: Mean diameter of proximal hyaloid vessels in pre-term pups was 25.44 +/- 1.98 microm; +/- 1 SEM). Within 3-12 hrs of birth, significant vasoconstriction was evident (diameter:12.45 +/- 0.88 microm), and normal hyaloid regression subsequently occurred. Similar vasoconstriction occurred in the O(2)-treated group, but this was reversed upon return to room air, with significant dilation of proximal vessels by D7 (diameter: 31.75 +/- 11.99 microm) and distal hyaloid vessels subsequently became enlarged and tortuous. CONCLUSIONS: Under normal conditions, vasoconstriction of proximal hyaloid vessels occurs at birth, preceding attenuation of distal hyaloid vessels. Vasoconstriction also occurs in O(2)-treated pups during treatment, but upon return to room air, the remaining hyaloid vessels dilate proximally, and the distal vessels become dilated and tortuous. These observations support the contention that regression of the hyaloid network is dependent, in the first instance, on proximal arterial vasoconstriction.

Delayed orbital hemorrhage after routine strabismus surgery.

PURPOSE: To report a case of delayed rectus muscle hemorrhage after strabismus surgery. METHODS: Case report. RESULTS: Rectus muscle hemorrhage occurred 36 hours after strabismus surgery in a 26-year-old man, causing temporary loss of vision and reduced ocular motility. Urgent lateral cantholysis and orbital exploration to restore hemostasis were undertaken. Full recovery of vision occurred and a small residual motility disturbance was present 3 months postoperatively. CONCLUSION: Delayed rectus muscle hemorrhage poststrabismus surgery is rare but can have sight-threatening effects. When vision is threatened because of optic nerve compromise, urgent orbital exploration may allow full recovery of function.

Vitreal macrophages express vascular endothelial growth factor in oxygen-induced retinopathy.

PURPOSE: The possibility of vitreal macrophages playing an angiogenic role in oxygen-induced retinopathy (OIR) was investigated. Oxygen-induced retinopathy was produced in newborn animals with the purpose of modeling the proliferative phase of human retinopathy of prematurity (ROP). MATERIALS AND METHODS: To produce OIR in neonatal mice, litters at postnatal day 7 were placed in 80-90% oxygen for a period of 5 days and then returned to room air. Pups were killed on days 7, 12, 15, 17 and 20 over the postnatal period and were perfusion-fixed using a saline wash-out, followed by 4% paraformaldehyde and then India Ink. Eyes were enucleated and either whole-mounted, or snap-frozen and cryosectioned. Immunostaining procedures were used to visualize macrophages and vascular endothelial growth factor (VEGF) protein. The primary antibodies used were anti-F4/80 and antimouse VEGF, respectively. Vitreal macrophages closely associated with the vitreo-retinal interface (within 25 microm of the inner limiting membrane) were counted. In situ hybridization procedures were used to analyse for the presence of VEGF mRNA transcript in vitreal macrophages. RESULTS: Macrophage numbers were found to significantly increase (P < 0.05) in eyes from oxygen-treated animals compared with those from age-matched controls. A close spatial relationship was observed between macrophages and vitreal neovascular sprouts. In addition, vitreal macrophages were also found to transcribe and express VEGF in the oxygen-treated animals during the vasoproliferative phase. CONCLUSIONS: Our results raise the possibility that vitreal macrophages play a role in the pathogenesis of OIR and by inference, ROP.

Late presentation of a unilateral sporadic retinoblastoma in a 16-year-old girl.

BACKGROUND: Retinoblastoma is the commonest intraocular tumour of childhood with the majority of cases being diagnosed before 5 years of age. Late presentation of retinoblastoma is rare. CASE HISTORY: A healthy 16-year-old Caucasian girl presented with a 1-day history of blurred vision in the left eye. Examination revealed an inferonasal mass in the left retina with an overlying haemorrhage and vitreous seeding. Imaging studies revealed a 5-mm densely calcified opacity. Other investigations, including cerebral spinal fluid examination, bone marrow aspirate trephine, toxocara serology and serum protein studies, were normal. After considering the differential diagnoses such as toxocariasis and Coat's disease, a diagnosis of late-presenting retinoblastoma was made. The patient subsequently underwent enucleation with a primary orbital implant. The diagnosis was confirmed histopathologically. CONCLUSION: Late presentation of retinoblastoma is uncommon but can be a cause of acute visual impairment in the non-paediatric age group. Retinoblastoma should be considered in the differential diagnosis of a fundal mass in any age group.

Autosomal dominant cataracts and Peters anomaly in a large Australian family.

Peters anomaly is a congenital corneal opacity with underlying defects in the posterior stroma, Descemets membrane and corneal endothelium. It is a disorder resulting from abnormal migration or function of neural crest cells and may include abnormalities of other anterior segment structures, such as the lens and iris. We report a family in which anterior segment abnormalities, including Peters anomaly and cataracts, were inherited in an autosomal dominant fashion. Although the PAX6 gene on chromosome 11 has been shown to be involved in some cases of anterior segment developmental defects, we found no evidence that the condition in this family is linked to the PAX6 gene. Identification of this gene will indicate another gene with major involvement in the development of the anterior segment of the eye.

Evaluating photoscreeners II: MTI and fortune videorefractor.

BACKGROUND: Amblyopia is a public health problem, usually amenable to treatment if detected early. Photoscreeners are camera-based instruments which can detect risk factors for amblyopia such as squint, refractive errors and media opacities. OBJECTIVE: To evaluate two commercially available photoscreeners, namely the MTI photoscreener (Medical Technology, Iowa City, IA, USA) and the Fortune Optical VRB-100 (Fortune Optical, Padova, Italy) videophotorefractor, in a selected childhood population, having a high prevalence of amblyopia, before undertaking a full-scale trial in the general population. SUBJECTS AND METHODS: The study design was a double-masked study. One-hundred and five children aged between 12 and 44 months with either normal vision or known visual disorders were photoscreened without cycloplegia using the Fortune and the MTI photoscreeners. Each child had a full ophthalmic examination either on the day of screening or in the preceding 6 months. Risk factors were: any manifest strabismus (squint), hypermetropia >3.5 D, anisometropia > or =1 D sphere, myopia > or =2 D sphere, astigmatism > or =2 D, media opacity or fundus abnormality affecting vision. The prevalence of risk factors for amblyopia was 60%. Photoscreen images were reviewed by two independent masked observers for indicators of amblyopiogenic risk factors and compared to the full ophthalmological examination to determine sensitivity and specificity for each instrument. RESULTS: Sensitivities and specificities for the detection of risk factors for amblyopia were as follows. Fortune photoscreener: reader 1, sensitivity 60%, specificity 75%; reader 2, sensitivity 68% specificity 86%. MTI photoscreener: reader 1, sensitivity 56%, specificity 79%; reader 2, sensitivity 61%, sensitivity 86%. The results for reader 1 and 2 showed no significant differences for either instrument. CONCLUSION: Both instruments performed unsatisfactorily in a study population aged 1-4 years with a high prevalence of amblyopiogenic risk factors. Accordingly, we do not believe that either instrument can be recommended to screen for eye disorders in children between the ages of 1 and 4 years because the low prevalence of amblyopia in this population demands very high sensitivity and specificity in order to avoid inappropriate over- or under-referral.

The nanophthalmic macula.

AIMS: To define an unusual macular appearance found in association with nanophthalmos. METHODS: A case review. RESULTS: Seven children (aged 8 months to 17 years) with nanophthalmos were examined. They all exhibited the same clinical findings of an unusual yellow macula appearance with retinal folds and crowded optic discs. Visual electrophysiology performed in four cases was normal. CONCLUSION: A distinctive yellow macular pigmentation with associated chorioretinal folds and crowded optic discs is present in nanophthalmos. It is proposed that the retinal folds are due to a disparity between scleral and retinal growth while the macula discoloration is due to a congenital abnormality in arrangement or position of the luteal pigment and is not degenerative. Included in this case series is the second case in the literature of nanophthalmos associated with Kenny's syndrome. Inheritance of nanophthalmos appears to be autosomal recessive.

Results of treatment of superior oblique overaction by silicone tendon-expander technique.

PURPOSE: To report the results of treatment of a series of patients with superior oblique overaction using the superior oblique silicone tendon-expander technique. METHODS: A chart review of 17 patients with superior oblique overaction who had a total of 26 silicone tendon-expander procedures was conducted. RESULTS: Mean preoperative degree of superior oblique overaction was +2.7. 92% of eyes had mild (+1) or no residual overaction at last postoperative assessment (follow-up range: 6 to 59 months). Of 15 patients with preoperative A-pattern of 10 prism diopter (delta) or more, only two patients (13%) had A-pattern of 10 delta or more at last assessment. Of 13 patients with preoperative hypotropia in primary position, five patients (38%) had no vertical deviation in primary position, and seven patients (54%) had persistent, but less vertical deviation in primary position at last assessment (mean reduced from 11 delta to 4 delta). No patient manifested superior oblique palsy at their last postoperative assessment. CONCLUSIONS: We believe that the superior oblique tendon-expander technique should be strongly considered for the treatment of superior oblique overaction associated with A-pattern or hypotropia in primary position, because it has a high success rate and a low incidence of postoperative complications. Consecutive superior oblique underaction did not occur in this series.

Angle-closure glaucoma after laser treatment for retinopathy of prematurity.

Laser photocoagulation has become the standard for treatment of retinopathy of prematurity. In general, it has been found to be a safe and effective means of retinal ablation. We report a case of angle-closure glaucoma in an infant after diode laser treatment for retinopathy of prematurity, which required bilateral surgical peripheral iridectomies.

Quantification of oxygen-induced retinopathy in the mouse.

PURPOSE: To describe a quantifiable model of vascular proliferation in oxygen-induced retinopathy (OIR) in the mouse. METHODS: Neonate Quackenbush mice were subjected to high-ambient oxygen (approximately 95%) for the first 5 days after birth, effecting a total inhibition of retinal vascular growth. Animals then were returned to room air, and the rates of subsequent vascular development in the plane of the retina and estimates of retinal capillary density were measured from flatmounts of ink-perfused eyes. Observations were confirmed with fluorescein isothiocyanate-lectin labeling of the peripheral vasculature. Abnormal growth of vascular sprouts into the vitreous was recorded from cross-sections. Observations in OIR were compared against those of age-matched control animals. RESULTS: The slower rate of retinal revascularization in OIR mice was quantified and compared against the normal rate. Lectin-binding studies confirmed the reliability of ink preparations. The number of vitreous sprouts in OIR peaked 8 to 10 days after animals were returned to room air (13 to 15 postnatal days). Sprouts then regressed, to disappear by postnatal day 20. In all respects, bar a slightly lower peripheral capillary density, the normal retinal vascular pattern was achieved in OIR within 15 days of exposure to room air (as opposed to the 10 days required in control mice). CONCLUSIONS: The protocol described for quantifying retinal proliferation in mouse OIR is reproduced readily, and the data recorded here will allow the effectiveness of subsequent treatments that may affect retinal vascular growth to be evaluated better.

Results of anterior transposition of the inferior oblique.

PURPOSE: We present the results of anterior transposition of the inferior oblique in a series of patients with inferior oblique overaction and dissociated vertical deviation (DVD). PATIENTS AND METHODS: We performed a retrospective study of 37 procedures on 21 patients who had unilateral or bilateral inferior oblique anterior transpositions. Before surgery, patients had +1 to +3 inferior oblique overaction and +1 (< 10 PD) or +2 (10 PD-20 PD) degree of DVD. The inferior oblique insertion was transposed to between 2 mm posterior to and 2 mm anterior to the temporal border of the inferior rectus insertion. Mean follow-up period was 27 months. RESULTS: Incidence of inferior oblique overaction of +2 or more was reduced from 84% before surgery to 16% at last postoperative assessments. Some 43% of eyes had no inferior oblique overaction and 86% had an improvement in the degree of inferior oblique overaction. At last assessments, 57% of eyes had no evidence of DVD and 68% of eyes had no evidence of DVD or an improvement in the degree of DVD. No patient who had unilateral anterior transposition developed hypotropia in primary position and there was no evidence of inferior oblique underaction in any patient at last assessment. Three patients requiring repeat inferior oblique surgery are discussed, including one patient who developed a large Y-pattern exotropia after bilateral anterior transposition of the inferior obliques. CONCLUSIONS: Inferior oblique anterior transposition has a place in the treatment of coexistent inferior oblique overaction and dissociated vertical deviation.