Chromosome abnormalities and the genetics of congenital corneal opacification.

Congenital corneal opacification (CCO) encompasses a broad spectrum of disorders that have different etiologies, including genetic and environmental. Terminology used in clinical phenotyping is commonly not specific enough to describe separate entities, for example both the terms Peters anomaly and sclerocornea have been ascribed to a clinical picture of total CCO, without investigating the presence or absence of iridocorneal adhesions. This is not only confusing but also unhelpful in determining valid genotype-phenotype correlations, and thereby revealing clues for pathogenesis. We undertook a systematic review of the literature focusing on CCO as part of anterior segment developmental anomalies (ASDA), and analyzed its association specifically with chromosomal abnormalities. Genes previously identified as being associated with CCO are also summarized. All reports were critically appraised to classify phenotypes according to described features, rather than the given diagnosis. Some interesting associations were found, and are discussed.

NYX-related Congenital Stationary Night Blindness in Two Siblings due to Probable Maternal Germline Mosaicism.

Background: Congenital Stationary Night Blindness (CSNB) is a clinically and genetically heterogenous inherited retinal disorder associated with nystagmus, myopia, strabismus, defective dark adaptation, and decreased vision. Pathogenic variants in at least 17 genes have been associated with CSNB, where a hemizygous variant of NYX causing an X-linked form of the disorder is among the commonest causes.Materials and Methods: A retrospective chart review of a single pedigree was performed. Three pediatric patients underwent ophthalmic examinations, visual electrophysiology, and ocular imaging. Molecular genetic testing for CSNB was pursued where clinically indicated.Results: Two male siblings demonstrated clinical and electroretinographic evidence of complete CSNB. Genetic testing identified a NYX pathogenic, in-frame deletion in both children. Targeted variant analysis of the mother failed to identify the variant in two independent samples, most consistent with mosaicism.Conclusions: Clinical and molecular analyses within the described family demonstrate the possibility of maternal mosaicism in NYX-related CSNB. The importance of cascade molecular testing is highlighted. The prospect of somatic or germline mosaicism in NYX-related CSNB informs genetic counseling, genetic testing decisions, and risk assessment in affected families.

Cerebroretinal microangiopathy with calcifications and cysts (CRMCC).

Extensive intracranial calcifications and leukoencephalopathy are seen in both Coats plus and leukoencephalopathy with calcifications and cysts (LCC; Labrune syndrome). Coats plus syndrome is additionally characterized by the presence of bilateral retinal telangiectasia and exudates while LCC shows the progressive formation of parenchymal brain cysts. Despite these apparently distinguishing features, recent evidence suggests that Coats plus and LCC represent the same clinical entity with a common primary pathogenesis involving a small vessel obliterative microangiopathy. Here, we describe eight previously unreported cases, and present an update on one of the original Coats plus patients to highlight the emerging core clinical features of the "cerebroretinal microangiopathy with calcification and cysts" (CRMCC) phenotype.

Penetrating orbital trauma by stiletto causing complex cranial neuropathies.

Penetrating orbital injuries pose a serious threat to vision, ocular motility, and in some cases, life. Long, sharp stiletto objects may penetrate deeply, causing catastrophic damage to orbital structures, despite seemingly trivial entry wounds. The authors present two cases of penetrating orbital injuries by stiletto objects, both entering via small eyelid wounds. Traumatic optic neuropathy occurred in both cases, and was treated with corticosteroids, however the globes escaped direct injury. Injuries to the IIIrd and VIth cranial nerves were also observed. Deep orbital injuries must be excluded in patients presenting with small eyelid wounds caused by sharp penetrating objects.

Management of inflammatory corneal melt leading to central perforation in children: a retrospective study and review of literature.

PURPOSE: To assess the outcome of early therapeutic penetrating keratoplasty (PKP) for corneal melt leading to perforation in children. METHODS: Case notes of all the consecutive patients presenting with acute corneal perforation that underwent urgent therapeutic PKP between 2000 and 2010 to the practice of one of the authors, both NHS at Great Ormond Street Hospital for Children and private, were retrospectively reviewed. Onset of perforation, underlying cause, medical and surgical treatment, pre- and post-operative visual acuity, graft clarity, length of follow-up, and post-operative complications were recorded. RESULTS: Four eyes of four consecutive patients (mean age of 9.5 years and median 8.5 years, range 4-17 years) were treated for acquired acute onset corneal perforations. There were three females and one male. Etiologies included herpes simplex keratitis secondary to immune recovery disease post bone marrow transplantation, acanthamoeba keratitis, recessive dystrophic epidermolysis bullosa, and blepharokeratoconjunctivitis with acne rosacea. Pre-operative visual acuity ranged from hand movements to 6/150. All the patients had severe anterior chamber inflammation. All eyes improved in visual acuity ranging from 6/9 to 6/18 with clear grafts at last follow-up. There was no recurrence of melt or perforation. Mean follow-up was 67 months (median 44 months). CONCLUSION: PKP during the acute phase together with aggressive medical therapy and close follow-up may achieve good visual outcomes in children with corneal melt with perforation and should be considered. Waiting may sometimes allow the marked inflammatory response seen in children to cause irreversible structural and/or functional damage.

Expression of FGFR-2 and FGFR-3 in the normal human fetal orbit.

AIMS: To demonstrate the expression patterns of two fibroblast growth factor receptors (FGFR-2 and FGFR-3) in the normal human fetal orbit. METHODS: 6 microm orbital slide sections were prepared from 12 week old human fetal material obtained within established ethical guidelines. Radioactive in situ hybridisation techniques were used to demonstrate the expression patterns of FGFR-2 and FGFR-3 within these sections. Only one foetus had appropriate orbital sections taken. RESULTS: FGFR-2 was expressed within the extraocular muscles (EOMs) and the optic nerve sheath and to a lesser degree within the orbital periosteal margins and the cranial sutures. FGFR-3 was expressed a lot within the periosteal margins and cranial sutures but not within either the EOMs or the optic nerve sheath. CONCLUSIONS: FGFR-2 and FGFR-3 are differentially expressed within different orbital components. FGFR-2 gene mutations may be responsible for craniosynostotic syndromes such as Crouzon, Pfeiffer, and Apert, while those in the FGFR-3 gene may cause isolated unicoronal synostosis. EOMs may be histologically abnormal in cases of Apert, Pfeiffer, and Crouzon syndromes but not isolated unicoronal synostosis. The pattern of expression of FGFR-2 in the normal human fetal orbit may explain some of the EOM histological findings seen in some cases of Apert, Pfeiffer, and Crouzon syndromes.

The achiasmia spectrum: congenitally reduced chiasmal decussation.

AIM: To describe the clinical spectrum of achiasmia, a congenital disorder of reduced relative decussation at the optic chiasm. METHODS: A retrospective case note and patient review of nine children (four boys). Achiasmia was defined by the combination of a characteristic asymmetry of the monocular visual evoked potential (VEP) response to flash and neuroimaging showing reduced chiasmal size. RESULTS: Three of the children had an associated skull base encephalocele with agenesis of the corpus callosum. In two patients achiasmia was associated with septo-optic dysplasia. Three patients had no neuroimaging abnormalities other than reduced chiasmal size and have no known pituitary dysfunction. One child had multiple physical deformities but the only brain imaging abnormality was reduced chiasmal size. CONCLUSIONS: Some children with disorders of midline central nervous system development, including septo-optic dysplasia and skull base encephaloceles, have congenitally reduced chiasmal decussation. Reduced relative decussation may co-exist with overall chiasmal hypoplasia. Children with an apparently isolated chiasmal decussation deficit may have other subtle neurological findings, but our clinical impression is that most of these children function well.

Management of intracorneal bleb after trabeculectomy for congenital glaucoma.

PURPOSE: Congenital glaucoma is a well-recognized entity that can occur in the presence of anterior segment dysgenesis. Trabeculectomy is an accepted intervention in the management of congenital glaucoma. The surgical technique as well as complications is well described. METHODS: This is a case report of a 3-month-old girl with anterior segment dysgenesis and glaucoma. She was referred post-trabeculectomy with persistent corneal opacity to be considered for penetrating keratoplasty and was found to have intrastromal corneal bleb. RESULTS: Ultrasound biomicroscopy confirmed communication of the corneal bleb with the anterior chamber, and the bleb was treated by autologous blood injection at the trabeculectomy site, under acetazolamide cover. CONCLUSIONS: We present evidence suggesting that abnormal structure was the etiologic basis for corneal bleb formation and describe our management of this previously unreported complication of trabeculectomy.

Ultrasound biomicroscopy of the eye in cystinosis.

OBJECTIVE: To describe the ocular ultrasound biomicroscopy (UBM) findings in patients with cystinosis. METHODS: Six patients with infantile nephropathic cystinosis, aged 16 to 25 years, and 6 controls (matched for age and spherical refractive error) were examined clinically and with UBM. Scleral reflectivity, corneal and iris thickness, central anterior chamber depth, angle width, trabecular meshwork to ciliary process distance, and ciliary sulcus width were measured. RESULTS: No patient had glaucoma or posterior synechiae, but all had crystals in the trabecular meshwork apparent with gonioscopy. Using UBM, the cornea and iris appeared similar in both groups, but the scleral reflectivity was increased in patients (P =.003). The angle was narrower in patients (mean +/- SD, 20 degrees +/- 7 degrees ) than controls (31 degrees +/- 5 degrees, P<. 001). The anterior chamber was shallower in patients (2556 +/- 197 microm) than controls (2968 +/- 284 microm, P<.001). The ciliary sulcus was closed or narrow in all patients (83 +/- 112 microm) compared with controls (339 +/- 135 microm, P<.001), with a reduction in the trabecular meshwork to ciliary process distance. CONCLUSIONS: This report of ocular UBM findings in cystinosis demonstrated narrowing of the angle and a ciliary body configuration similar to that reported for plateau iris syndrome. Gonioscopy demonstrated crystals in the trabecular meshwork. These findings may explain the predisposition of these patients to glaucoma.

Latanoprost in port wine stain related paediatric glaucoma.

AIM: To evaluate the efficacy of latanoprost (Xalatan) as adjunctive therapy in port wine stain related paediatric glaucoma. METHODS: A retrospective non-randomised study. Patients with previous surgical intervention and medical treatment were included. Measurements were recorded from clinic and/or examination under anaesthetic (EUA) visits. A successful outcome was considered to be patients who required no further intervention following initiation of latanoprost, with stable glaucoma factors as well as drop in intraocular pressure. RESULTS: 14 patients and 17 eyes were reviewed in total. The mean age of glaucoma diagnosis was 2.59 years (0.1-5.25 years) and of commencing latanoprost was 6.8 years (1.40-12.90 years). Percentage success at 1 month, 3 months, 6 months, and 1 year was 70.6%, 64.7%, 58.9%, and 47.1%, respectively, of eyes treated which translated to 71.4%, 64.2%, 57.1%, and 50% respectively of patients treated. CONCLUSIONS: A trial of latanoprost as adjunctive therapy in patients with port wine stain related glaucoma may temporise the need for surgery; with 50% of patients being controlled at 1 year follow up. Lack of efficacy was detected as early as 1 month following commencement of treatment.

An ultrasound based classification of periocular haemangiomas.

AIMS: To propose a classification system for periocular haemangiomas based on ultrasound evaluation. METHODS: Retrospective review of ultrasound images from children seen in the authors' unit with periocular haemangiomas. Static ultrasound images from 50 patients with periocular haemangiomas were reviewed as identified from a computerised database. Each haemangioma ultrasound image was classified into three categories: (1) preseptal only; (2) preseptal + extraconal; (3) preseptal + extraconal + intraconal. These were compared with the categories given to each patient at first presentation after dynamic scanning. RESULTS: Classification was possible from the static images in 44 (88%) cases. Of those classified 20 (45%) were preseptal only; 17 (39%) were preseptal + extraconal, and seven (16%) had an additional intraconal component. The classification in all 44 cases was the same as that given at the time of presentation. In the small number of cases which went to surgery or had neuroimaging, the ultrasound classification was confirmed. CONCLUSIONS: Ultrasound classification was not difficult to perform and no child needed sedation or general anaesthesia for this exam. Ultrasound anatomical classification is an important first step in determining appropriate treatment of periocular haemangiomas. The authors present what they believe to be the first such classification.

Visual outcomes and amblyogenic risk factors in craniosynostotic syndromes: a review of 141 cases.

AIMS: To determine the visual outcome and prevalence of amblyogenic risk factors in children with craniosynostotic syndromes. METHODS: The case notes of 141 children seen within the craniofacial unit were reviewed and information retrieved on date of birth, age at first and last examination, cycloplegic refraction at last visit, best corrected visual acuity at last visit, horizontal ocular deviation in primary position at first visit, and alphabet pattern if any. The presence of astigmatism, its magnitude, and orientation of axis were determined. RESULTS: 40.3% of patients had 1 dioptre (D) of astigmatism or greater and, of these, 64% had oblique astigmatism in at least one eye. Anisometropia of 1D or more was found in 18% of patients (age matched normals 3.5%). Horizontal strabismus was found in 70% (38% exotropia, 32% esotropia). Visual outcome results showed 39.8% of patients (45 of 113) had visual acuity of 6/12 or worse in their better eye. CONCLUSION: In the largest study to date a poor visual outcome was shown in children with Crouzon's, Pfeiffer's, Apert's, and Saethre-Chotzen syndromes (39.8% with 6/12 or worse in the better eye) together with significant prevalence of amblyogenic risk factors.

Clinicopathological correlation of congenital corneal opacification using ultrasound biomicroscopy.

AIM: To investigate the correlation between clinical, high frequency ultrasound biomicroscopy (UBM) and, where possible, histological findings in cases of congenital corneal opacification presenting to the departments of ophthalmology, Great Ormond Street Hospital for Children, London, and the Hospital for Sick Children, Toronto, Canada. METHOD: 22 eyes of 13 children (age range 3-225 days) with congenitally opaque corneas were examined. UBM was performed using the ultrasound biomicroscope (Allergan-Humphrey). All eyes underwent penetrating keratoplasties (PKP) except five. The host corneas were all sent for histological examination. RESULTS: The final diagnosis in our series was Peters' anomaly in nine cases (70%), corneal dystrophy in two cases (15%), and sclerocornea in two cases (15%). The UBM findings changed the clinical diagnosis in five cases (38%). In these five cases histology was available in four and confirmed the UBM diagnosis in each case. In no case of the 13 where histology was available did it contradict the UBM findings. In two cases a hypoechoic region in the anterior stroma was seen on UBM which correlated histologically with absent Bowman's layer and oedema. In two cases UBM revealed aniridia and in one, congenital aphakia, which was not apparent clinically. CONCLUSION: UBM examination is not only very useful in evaluating the clinical diagnosis in congenital corneal opacification, it also acts as a preoperative guide in cases undergoing PKP by detecting keratolenticular and iridocorneal adhesions and other ocular abnormalities such as aniridia and congenital aphakia. In all cases where PKP was performed the UBM diagnosis was confirmed histologically. The clinical diagnosis was incorrect in five cases. This has important implications in studies of phenotype/genotype correlation of congenital corneal opacification.

Effect of applanation tonometry on mean corneal curvature.

PURPOSE: To evaluate whether applanation tonometry affects corneal curvature and if so, the implications for intraocular lens power calculation. SETTING: Birmingham and Midland Eye Hospital, Birmingham, England. METHODS: Twenty-two patients attending the preoperative assessment clinic were enrolled in the study. Keratometry was performed immediately before, 1 minute after, and 10 minutes after standard Goldmann tonometry. Main outcome measures were mean corneal refractive power and its reproducibility (coefficient of repeatability). RESULTS: No clinically significant difference was noted between preapplanation and postapplanation readings (P = .6), and reproducibility was not significantly affected. CONCLUSION: The results indicate that corneal applanation before keratometry does not compromise the prediction of postoperative refraction.

High-frequency ultrasonography findings in persistent hyperplastic primary vitreous.

PURPOSE: To identify anatomic correlates in eyes with persistent hyperplastic primary vitreous (PHPV) by using high-frequency ultrasonography. METHOD: Three main groups of patients were studied by means of high-frequency ultrasonography over a 19-month period. Group I included 9 eyes of 9 patients with newly diagnosed unilateral PHPV. Group II included 4 eyes of 4 patients with unilateral PHPV that had been previously surgically treated. Group III included 22 eyes and was a control group of patients without PHPV. This group consisted of the 5 contralateral normal eyes of 5 patients with unilateral PHPV in the fellow eye, both eyes of one patient with uncomplicated unilateral cataracts, the affected eye of one patient with unilateral uncomplicated cataract, the affected eye of one patient with isolated retinal coloboma, and 13 normal eyes of 7 young adults. Group I and II patients also had B-scan ultrasonography performed and had any intraoperative findings noted. RESULTS: Characteristic features of PHPV, such as centrally dragged ciliary processes and swollen anteriorly displaced lens, were observed only in those eyes with PHPV. A new echographic finding of a double linear echo was observed in the region of the pars plana or plicata only in eyes with PHPV. This finding was confirmed intraoperatively to be consistent with a thickened adherent anterior hyaloid face and not to be an anteriorly inserted peripheral retina. CONCLUSION: High-frequency ultrasound can be reliably used to distinguish characteristic features of PHPV. To our knowledge this is the first such description of the use of high-frequency ultrasonography in PHPV eyes. Furthermore, the presence of a thickened adherent anterior hyaloid face may help explain the well-recognized complications of peripheral retinal tears and retinal detachments during and after surgical intervention.

Bilateral symmetrical branch retinal artery occlusions.

We present a report of a 52-year-old hypertensive patient with documented bilateral symmetrical branch retinal artery occlusions involving the maculae. The patient presented with no visual symptoms and maintained 6/5 unaided visual acuity in each eye. Although the incidence of retinal artery occlusion in hypertensive patients is well documented, symmetrical bilateral branch retinal artery occlusions suggest a possible anatomical vascular predisposition.

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 7 years, range 1.5-13.8 years) were identified. Median follow-up was 18 months. 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 6 months 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.

Incidence of early-onset glaucoma after infant cataract extraction with and without intraocular lens implantation.

AIMS: To determine the incidence of glaucoma, with onset within 1 year after the date of cataract surgery (early onset) performed in the first year of life, with or without intraocular lens (IOL) implantation. METHODS: A retrospective review of a single surgeon's cohort from 1999 to 2006. Glaucoma onset risk, comparison of aphakic/pseudophakic eyes and IOL type were analysed together with microcornea, persistent fetal vasculature (PFV) and age < or =4 weeks at surgery. RESULTS: Ninety-eight eyes (62 patients; mean age 2.88 months) were included with 61 eyes (36 patients) aphakic (57 planned and four failed implantations), and 37 eyes (26 patients) pseudophakic. At a mean follow-up of 2.51 years,15.3% (12.2% within 1 year) of all eyes, 9.8% of eyes (6.6% within 1 year) in the planned aphakic group, all four eyes with failed implantation and 13.5% of the pseudophakic eyes (10.8% within 1 year) developed glaucoma. Glaucoma incidence stratified by absence or presence of IOL showed no statistically significant difference, but eyes in the rigid polymethylmethacrylate group had an increased glaucoma risk compared with the Acrysof group (p = 0.002). Microcornea, PFV and age < or =4 weeks at surgery were not significant predictors of early-onset glaucoma. CONCLUSIONS: In this single surgeon study of infant cataract surgery only, age < or =4 weeks at surgery was not a predictor of early-onset glaucoma. The rate of aphakic and pseudophakic early-onset glaucoma was not found to be statistically different, but we found a statistically different rate of glaucoma between the two IOL types which needs further evaluation, given that this is a retrospective review. Excessive surgical trauma influences incidence of glaucoma.