Calibration of the PlusOptix PowerRef 3 with change in viewing distance, adult age and refractive error.

PURPOSE: The PowerRef 3 is frequently used in studying the near triad of accommodation, vergence and pupil responses in normal and clinical populations. Within a range, the defocus measurement of the PowerRef 3 is linearly related to the eye's defocus. While the default factory-calibrated slope of this relation (calibration factor) is 1, it has been shown that the slope can vary across individuals. Here, we addressed the impact of changes in viewing distance, age and defocus of the eye on the calibration factor. METHODS: We manipulated viewing distance (40 cm, 1 m and 6 m) and recruited participants with a range of accommodative capabilities: participants in their 20s, 40s and over 60 years old. To test whether any effect was larger than the range of measurement reliability of the instrument, we collected data for each condition four times: two in the same session, another on the same day, and one on a different day. RESULTS: The results demonstrated that viewing distance did not affect the calibration factor over the linear range, regardless of age or uncorrected refractive error. The largest proportion of the variance was explained by between-subject differences. CONCLUSIONS: Calibration data for the PowerRef 3 were not sensitive to changes in viewing distance. Nevertheless, our results re-emphasise the relevance of calibration for studies of individual participants.

Early diagnosis of Stargardt disease with multifocal electroretinogram in children.

To present two pediatric cases where multifocal electroretinogram (mfERG) was able to establish an earlier diagnosis compared to full field electroretinogram (ERG) Case 1: an 11-year-old boy with reduced visual acuity, pale discs, macular pigmentation with white dots bilaterally. Case 2: a 12-year-old girl with reduced vision in her right eye, slight pallor of the right optic disc, intense pigmentation at both maculae and scattered punctate lesions throughout the peripheral fundi. Both had been investigated with electrodiagnostic tests according to the International Society of Clinical Electrophysiology for Vision protocol. Full-field ERGs for both children showed normal responses. Case 1: mfERG revealed a severe reduction in function in the inner 20°. Case 2: mfERG showed attenuated responses in each eye. Clinical examination and mfERG were consistent with Stargardt disease. mfERG is applicable to children and is a sensitive tool for early diagnosis of retinal dystrophies.

Measures and variability with age of low contrast acuity and near stereoacuity in children.

CLINICAL RELEVANCE: Low contrast acuity (LCA) and near stereoacuity (NS) testing are integral to the comprehensive assessment of sensory visual function in children. However, routine ophthalmological evaluations seldom take these measures into consideration. Additionally, there is limited literature regarding the normative values of these parameters in children. BACKGROUND: This study investigated LCA and NS measures and their variability in children with normal visual acuity. The aim was to provide a benchmark for distinguishing normal measures from abnormal ones. METHODS: A prospective observational study was conducted in primary and secondary schools across North India. The participants numbered 240 children, aged between 3 and 15 years. They were split into 12 smaller groups of 20 participants in each age group. Only participants with normal monocular uncorrected visual acuity, no refractive error, normal birth history, and no systemic ailments, were recruited. All the participants underwent a complete ophthalmic examination and non-cycloplegic retinoscopy. LCA was measured, using the low contrast Lea number chart at three metres. NS was measured using the Randot® stereo test at 40 cm. RESULTS: The percentages of males and females, were found to be 55%, and 45%, respectively (p = 0.093). The mean NS was found to be 38.7 ± 11.5 arcsecs in the 3-9-year age group, and 26.7 ± 5.6 arcsecs in the 9-15-year age group (p-value <0.001). The mean NS showed an increasing trend up to 9 years of age. The mean LCA was 64.4 ± 20.1 in the age group of 3-8 years, and 76.38 ± 11.39 in the age group of 8-15 years (p-value <0.001). Considerable variability was noted in the LCA in the younger age group (p-value = 0.000). CONCLUSIONS: LCA and NS mature gradually during childhood. LCA stabilises after the age of 8, while NS stabilises after the age of 9.

Abatacept: a potential therapy in refractory cases of juvenile idiopathic arthritis-associated uveitis.

BACKGROUND: Juvenile idiopathic arthritis (JIA) is the most common of all systemic conditions associated with childhood uveitis. Visual impairment has been shown to be as high as 40% of which 10% being blind (6/60 or worse). Due to the lack of well-designed randomized control trials for paediatric uveitis and arthritis there are limited comparative data regarding the efficacy of single or combination treatments. Recently, abatacept was shown to control ocular inflammation in a case of psoriatic arthritis- associated uveitis, seven cases of JIA- associated uveitis and in JIA. We present two cases with JIA-associated uveitis who have responded dramatically to abatacept therapy following unsuccessful therapy with other immunosuppressants. Control of arthritis still represents a challenge with this treatment. METHODS: Prospective review of two patients with refractory JIA- associated uveitis not responding to maximum conventional treatment. Patients were regularly reviewed in the ophthalmology and rheumatology clinics. Assessment of their ocular condition was characterized according to the Standardization of Uveitis Nomenclature (SUN) group. RESULTS: In case 1, ocular inflammation was brought under control after repeated abatacept infusions. Case 2 showed complete resolution of cystoids macular edema CME and improvement of 5 Snellen's lines in best corrected visual acuity. After 9 months, the ocular condition of both patients remains in remission with steroid sparing. Joint disease was brought to clinical remission in case 2, but not in case 1. CONCLUSIONS: Abatacept is a promising alternative treatment in refractory cases of JIA uveitis but may not be as successful in controlling joint disease. Larger series with long term follow up of biological therapies in paediatric uveitis are essential to assess the efficacy and cost effectiveness.

Higher Visual Function Deficits in Children With Cerebral Visual Impairment and Good Visual Acuity.

In clinical practice Cerebral Visual Impairment (CVI) is typically diagnosed by observation of abnormal visually guided behaviors which indicate higher visual function deficits (HVFDs) suggesting abnormal brain development or brain damage in a child with a suitable clinical history. HVFDs can occur even in the presence of good visual acuity and may remain undiagnosed because the good visual acuity does not prompt further investigation. This leads to a lack of understanding of the child's visual perceptual difficulties. In a prospective study, we determined the spectrum of HVFDs in a group of children with history suggestive of brain damage or disruption of brain development and an independent diagnosis of CVI in comparison with typically developing children with a structured 51 question inventory, the Higher Visual Function Question Inventory (HVFQI-51) adapted from the Cerebral Vision Impairment Inventory, CVI-I. Here, we show that the HVFQI-51 can detect a range of HVFDs in children with CVI with good visual acuity and clearly distinguishes these children from typically developing children. HVFDs in our study group could mostly be attributed to dorsal stream visual processing dysfunction though the spectrum varied between children. We report on the inclusion of the "not applicable" response option in analysis providing a picture of HVFDs more in tune with the overall disability of each child. We also propose a subset of 11 questions (Top-11) which discriminate between children with CVI vs. behaviors seen in typical children: this provides both a potential screening tool for initial assessment of HVFDs and a measure of CVI-related impairment, and needs further validation in a secondary independent sample.

Motion Processing Deficits in Children With Cerebral Visual Impairment and Good Visual Acuity.

Purpose: We sought to characterize neural motion processing deficits in children with cerebral visual impairment (CVI) who have good visual acuity using an objective, quantifiable method (steady-state visual evoked potentials [SSVEPs]). Methods: We recorded SSVEPs in response to three types of visual motion - absolute motion and more complex relative and rotary motion, comparing them to form-related vernier and contour responses. We studied a group of 31 children with CVI diagnosed via detailed clinical examinations and 28 age-matched healthy controls. Results: Using measurements made at the appropriate response harmonics of the stimulation frequency, we found significant deficits in cerebral processing of relative and rotary motion but not of absolute motion in children with CVI compared with healthy controls. Vernier acuity, in keeping with good recognition acuity in both groups, was not different, nor were contour-related form responses. Conclusions: Deficits for complex motion but relative sparing of elementary motion and form-related signals suggests preferential damage to extra-striate visual motion areas in children with CVI. The fact that these preferential losses occur in the absence of significant acuity loss indicates that they are not secondary to reduced visual acuity, but rather are an independent vulnerability in CVI. These results corroborate parental and caregivers' reports of difficulties with tasks that involve motion perception in children with CVI.

A covered eye fails to follow an object moving in depth.

To clearly view approaching objects, the eyes rotate inward (vergence), and the intraocular lenses focus (accommodation). Current ocular control models assume both eyes are driven by unitary vergence and unitary accommodation commands that causally interact. The models typically describe discrete gaze shifts to non-accommodative targets performed under laboratory conditions. We probe these unitary signals using a physical stimulus moving in depth on the midline while recording vergence and accommodation simultaneously from both eyes in normal observers. Using monocular viewing, retinal disparity is removed, leaving only monocular cues for interpreting the object's motion in depth. The viewing eye always followed the target's motion. However, the occluded eye did not follow the target, and surprisingly, rotated out of phase with it. In contrast, accommodation in both eyes was synchronized with the target under monocular viewing. The results challenge existing unitary vergence command theories, and causal accommodation-vergence linkage.

Differential Experience-Dependent Plasticity of Form and Motion Mechanisms in Anisometropic Amblyopia.

Purpose: We measure neural responses associated with form and motion processing in children with anisometropia before and after treatment with spectacles and occlusion. Methods: In this prospective, case-control treatment study, 10 children with anisometropia and amblyopia and 16 age-matched visually normal children participated. Steady-state visual evoked potentials (VEP) were recorded from electrodes over the occipital cortex. The visual stimulus comprised a horizontal bar grating into which Vernier offsets were introduced and withdrawn periodically at 3.75 Hz. The VEP amplitude at 3.75 Hz (first harmonic [1F]) and 7.5 Hz (second harmonic [2F]) were recorded to index the sensitivity of form/position-sensitive versus motion/transient-sensitive neural populations, respectively. Response amplitude at 1F and 2F were recorded over a series of 10 logarithmically spaced offset sizes before and after treatment. Main outcome measures are VEP amplitude versus displacement functions, interocular response amplitude differences. Results: After relaxing into spectacles (minimally-treated state), form/position-sensitive responses in the dominant/less ametropic eye of the children with anisometropia were larger and responses in the more ametropic eye were smaller than those of controls. Motion-transient responses were equal to those of controls in the less ametropic eye, but were smaller than controls in the more ametropic eye. After treatment, responses did not differ from those of controls. Conclusions: Form and motion responses are differentially susceptible to neural deprivation via optical blur. Form responses are more plastic than motion responses in minimally-treated children with anisometropic amblyopia. Most treatment effects occurred above threshold range, suggesting some treatment effects are not detected clinically.

Vision impairment with an interstitial deletion of the short arm of chromosome 8.

We describe the phenotype of a male infant with an interstitial deletion of the short arm of chromosome 8 (p. 11.2-p. 21). Visual impairment is a major feature in this case. The clinical, radiographic and electrodiagnostic findings are presented. Only four other cases have been reported in which visual problems are associated with a deletion of 8 p.

The differential diagnosis of vertical strabismus from prism cover test data using an artificially intelligent expert system.

An expert system is described for the differential diagnosis of vertical deviation strabismus (squint) from measurements taken in the standard prism cover test. The deviations are represented as optical powers in prism dioptres using the graphic representation of strabismus (after Jampolsky). The expert is implemented in MatLab (Mathworks Ltd., Cambridge, UK) both as a stand-alone program on a PC and as a web application available over the Internet (see http://www.strabnet.com ). In trial and clinical datasets a diagnostic accuracy of 100% was achieved.

The repeatability of best corrected acuity in normal and amblyopic children 4 to 12 years of age.

PURPOSE: The main purpose of this work was to measure repeatability of line-by-line logMAR (logarithm of the minimum angle of resolution) acuity in normal and amblyopic children, while adequately controlling for optical defocus. METHODS: The Lea Symbols Chart is a constant-crowding, equal-logMAR increment chart similar in design to the Early Treatment Diabetes Retinopathy Study [ETDRS] chart. LogMAR visual acuity was tested twice in each eye of 32 amblyopic and 11 normal children. Each test commenced with screening in which one of the three central symbols was chosen for identification starting with the 1.0- or 0.9-logMAR line, progressing to every second line until incorrect identification occurred. Symbol-by-symbol presentation then commenced at the logMAR line containing the last correctly identified symbol. The threshold was recorded as the last logMAR line where four of four or four of five correct responses occurred (i.e., line-by-line scoring). Retesting by the same examiner was identical and occurred within the same session. RESULTS: There was no significant difference in repeatability among normal, fellow, or amblyopic eyes. The difference between test and retest thresholds lay between +/-0.10 logMAR in 93% of eyes. The 95% limits of agreement for the difference was +/-0.18 logMAR. Repeatability in eyes tested first did not differ from that in those tested second in either the normal or amblyopic groups. CONCLUSIONS: In the age-group tested, the line-by-line method of threshold scoring compares favorably with previous reports of both line-by-line and interpolated threshold scoring. There was no clinically meaningful difference in repeatability between the normal and amblyopic children tested.

Description of a new syndrome: auricular abnormalities and cleft lip in two sibs, in association with cleft palate and unusual opthalmological findings.

We describe the association of auricular abnormalities and cleft lip with or without cleft palate in two siblings. One sibling has postauricular pits, profound myopia, nystagmus and retinal pigment abnormalities. The second sibling was a fetus of 23 weeks gestation with severe cleft lip, cleft palate and external ear abnormalities. As this constellation of features has not been described together before, we believe this is a new syndrome.

Multifocal choroiditis with panuveitis in an 8-year-old boy with long-standing idiopathic acute anterior uveitis.

PURPOSE: To report successful treatment of a rare case of sight-threatening pediatric multifocal choroiditis with panuveitis (MFCPU) and the use of electrophysiology to confirm return of macular function. METHODS: Case report. RESULTS: An 8-year-old boy with a history of bilateral recurrent non-juvenile idiopathic arthritis acute anterior uveitis (AAU) presented with new-onset blurry vision and floaters in both eyes. Visual acuity had deteriorated to 20/200 right eye and 20/100 left eye. Cells were observed in the anterior chamber and vitreous of both eyes. Ophthalmoscopy showed multiple active small cream-colored chorioretinal lesions and cystoid macular edema (CME) in both eyes in the absence of systemic disease, suggestive of idiopathic MFCPU. Successful rapid visual recovery and resolution of CME confirmed by spectral-domain optical coherence tomography (SD-OCT) was achieved with prompt intensive systemic steroid therapy followed by early introduction of methotrexate. After 9 months, his visual acuities improved to 20/32, and pattern reversal visual evoked potentials and 19 hexagon multifocal electroretinography posttreatment were normal, showing recovery of macular function. CONCLUSIONS: Multifocal choroiditis with panuveitis is rare in children and has not been documented in the presence of previous longstanding recurrent AAU. Onset of floaters in children should alert the clinician to early stages of posterior pole involvement and progression to reduction in vision due to CME requires prompt aggressive steroid therapy monitored by clinical examination, SD-OCT, and electrophysiology, followed by early introduction of immunosuppressive drugs for long-term stability and to avoid steroid-induced adverse effects in children.

Measurement of position acuity in strabismus and amblyopia: specificity of the vernier VEP paradigm.

PURPOSE: An objective measure of positional acuity is desirable in the nonverbal clinical population. This study was conducted to investigate the specificity of the vernier VEP as a measure of positional acuity, evaluating the potential confound of asymmetric motion responses that may be present in some groups of patients. These motion responses could masquerade as position-specific responses, since they occur at the same response frequency as the vernier-related response. METHODS: Twelve observers with early-onset esotropia (EOE), 30 children with untreated amblyopia, and 15 control children underwent swept vernier VEP acuity testing accompanied by a swept motion control stimulus. The control condition was used to detect the presence of artifactual responses not related to position sensitivity. The patients with EOE were selected for high levels of motion asymmetry as documented with oscillating gratings presented monocularly. As a measure of motion confound (penetration), the proportion of first-harmonic responses recorded in the control condition was determined. RESULTS: The penetration rate in the vernier condition in each study group (EOE: 0.93%; amblyopes: 4.26%; normal subjects: 2.40%) and the entire group (2.85%) was acceptably low. The level of penetration was not significantly influenced by the presence of amblyopia. CONCLUSIONS: The vernier VEP paradigm, when applied in the manner described, can be interpreted as a measure of position sensitivity. The presence of motion asymmetry or untreated amblyopia does not affect the validity of vernier measurements made.

CRYBB1 mutation associated with congenital cataract and microcornea.

PURPOSE: The molecular characterization of a UK family with an autosomal dominant congenital cataract associated with microcornea is reported. METHODS: Family history and clinical data were recorded. This phenotype was linked to a 7.6 cM region of chromosome 22q11.2-q12.2, spanning the beta-crystallin gene cluster (ZMax of 3.91 for marker D22S1114 at theta=0). Candidate genes were PCR amplified and screened for mutations on both strands using direct sequencing. RESULTS: Sequencing of the coding regions and flanking intronic sequences of CRYBB2 and CRYBB1 showed the presence of a novel, heterozygous X253R change in exon 6 of CRYBB1. SSCP analysis confirmed that this sequence change segregated with the disease phenotype in all available family members and was not found in 109 ethnically matched controls. CONCLUSIONS: X253R is predicted to elongate the COOH-terminal extension of the protein and would be expected to disrupt beta-crystallin interactions. This is the first documented involvement of CRYBB1 in ocular development beyond cataractogenesis.

Recovery of contour integration in relation to LogMAR visual acuity during treatment of amblyopia in children.

PURPOSE: In several studies, researchers have found that integration of orientation information along contours defined by Gabor patches is abnormal in patients with strabismus and in untreated patients with anisometropic amblyopia. In this study, the rate and degree of recovery of contour-integration deficits were compared with the recovery of logMAR (logarithm of the minimum angle of resolution) visual acuity deficits in patients newly diagnosed with amblyopia secondary to anisometropia, strabismus, or both. METHOD: Contour-detection thresholds and optotype acuity were measured in 17 newly diagnosed anisometropic amblyopes, in 6 patients with strabismic amblyopia, and in 4 patients with combined anisometropic and strabismic amblyopia. Contour-detection thresholds were measured with a card-based procedure. Treatment comprised full refractive correction and full-time total occlusion therapy, when necessary. Visual function was measured at monthly visits during the course of treatment, with an average follow-up period of 16 weeks (12-24 weeks) for the entire group. Complete data were obtained from 23 patients through 8 weeks of follow-up. RESULTS: Significant interocular differences in contour-detection thresholds were present in 16 of the 27 patients at the first visit after initial refractive correction. Interocular differences in contour-detection thresholds declined to normal levels in most of the patients within 8 weeks of the initiation of treatment. Interocular acuity differences remained significant in many of the patients (19/23) at 8 weeks of follow-up and continued to decline, but did not fully normalize, over the remainder of the follow-up period. CONCLUSIONS: Refractive correction alone or in combination with occlusion therapy produces a normalization of contour-integration thresholds in amblyopia that is more rapid and complete than that achieved for visual acuity.

Propranolol and periocular capillary hemangiomas: assessment of refractive effect.

PURPOSE: To assess the effects of systemic propranolol on refractive error in infants with periocular capillary hemangiomas. METHODS: A single-center study of consecutive patients with capillary hemangiomas treated with systemic propranolol. Refractive data were analyzed using Long's matrix formalism and the methods of Harris and Kaye. RESULTS: Seventeen patients were included. At 6 months postoperatively, hemangioma size reduced from 3,214 to 1,806 mm(3) (standard deviation: 4,122 to 2,441). Mean refractive error in the affected eye significantly reduced: -1.25/0.38 × 36 (95% confidence intervals: -5.08/1.20 × 90 to 1.64/1.43 × 180, P = .048) with a smaller change (P = .06) in the unaffected eye of -1.01/+0.31 × 3.16 (95% confidence intervals: -4.02/+1.12 × 180 to +1.49/+0.51 × 90). CONCLUSIONS: Propranolol produced a clinically significant reduction in the infants' refractive error and anisometropia. The reduction in the total refractive error and anisometropia has not been evident in previous analyses, which have concentrated on the change in the "cylinder" as the principal outcome measure.

Presentation of suspected pediatric uveitis.

UNLABELLED: Presentation of suspected pediatric uveitis: Pediatric uveitis is usually managed in specialized ophthalmic centers in the UK. Meaningful data acquisition in these clinics may be helpful in clinical governance, and healthcare planning in a specialty that is gradually changing due to changes in treatment choices. METHODS: Retrospective analysis of prospectively acquired data in the Liverpool pediatric uveitis database was performed. RESULTS: Analysis of our data, based on 147 patients, with a mean age of 10 years, indicated a female to male ratio of 2:1. 99% of patients were Caucasian. Our data indicates 86% of all patients attending the uveitis clinic were diagnosed with juvenile idiopathic arthritis, followed by intermediate uveitis 5% and idiopathic uveitis 4%. 46% of patients required treatment. Systemic treatment included methotrexate (34%), prednisolone (14%), etanercept (6%), ciclosporin (6%), mycophenolate (3%), and infliximab (1%). Severe visual loss (defined by counting fingers or below vision) was seen in 10 eyes despite appropriately treated chronic uveitis. CONCLUSION: Our data shows uveitis-related ocular morbidity in a predominantly pediatric Caucasian population. Patients with severe and chronic uveitis may experience significant uveitis-related complications and subsequent visual loss despite aggressive treatment.

Etanercept in methotrexate-resistant JIA-related uveitis.

UNLABELLED: We report our results with systemic Etanercept in patients with juvenile idiopathic arthritis in a joint ophthalmology-rheumatology clinic at a tertiary hospital. METHODS: Patients with JIA on Etanercept were identified from a dedicated uveitis database. A retrospective review of electronic and paper-based patient records was performed. RESULTS: Nine patients with JIA and current or previous treatment with Etanercept were identified, including six females and three males. Five patients with previous or current uveitis were noted. A further four were under observation for uveitis and required Etanercept for their joint disease. All nine patients had previously been taking Methotrexate, which had a suboptimal response in controlling arthritis or uveitis. Six out of nine patients did not show any uveitis activity at their last follow-up. Eyes of three patients still show signs of active inflammation in the anterior chamber (two on Etanercept and one off Etanercept). Severely impaired visual acuity (PL) was recorded in both eyes of one patient with long-standing persistent uveitis. Moderate visual loss in one eye of one patient was seen. The remaining seven patients did not show any significant loss of vision. Intraocular inflammation was not induced in any patient started on Etanercept. CONCLUSION: Etanercept may be useful in controlling JIA-related uveitis or arthritis in a pediatric patient when Methotrexate has had a suboptimal response in controlling the inflammatory activity.

Corneal endothelial dysfunction in Pearson syndrome.

Mitochondrial disorders are associated with well recognized ocular manifestations. Pearson syndrome is an often fatal, multisystem, mitochondrial disorder that causes variable bone marrow, hepatic, renal and pancreatic exocrine dysfunction. Phenotypic progression of ocular disease in a 12-year-old male with Pearson syndrome is described. This case illustrates phenotypic drift from Pearson syndrome to Kearns-Sayre syndrome given the patient's longevity. Persistent corneal endothelial failure was noted in addition to ptosis, chronic external ophthalmoplegia and mid-peripheral pigmentary retinopathy. We propose that corneal edema resulting from corneal endothelial metabolic pump failure occurs within a spectrum of mitochondrial disorders.