Social and Quality-of-Life Impact of Refractive Surgery in Children With Developmental Disorders and Spectacle Nonadherence.

PURPOSE: Children with autism spectrum disorder and intellectual disability often cannot tolerate wearing spectacles or contact lenses, which are the standard-of-care for treating ametropia.1,2 We aimed to assess the impact of refractive surgery on social functioning and vision-specific quality-of-life (VSQOL) in this population. DESIGN: Prospective, before-and-after case series. METHODS: Setting: Single, academic tertiary care center. STUDY POPULATION: 18 children with autism spectrum disorder and/or intellectual disability, ametropia, and spectacle nonadherence were included in the analysis. PROCEDURE: Participants underwent refractive surgery with either intraocular lens implantation or keratectomy. Parents completed the Social Responsiveness Scale (SRS-2) and Pediatric Eye Questionnaire (PedEyeQ) at baseline and 1, 6, and 12 months postsurgery.3,4 Main outcome measures: Median change in SRS-2 T-scores and PedEyeQ scores 12 months after surgery, compared to baseline. The minimum clinically important difference was set at 5 points for the SRS-2 and 10 points for the PedEyeQ. RESULTS: At 12 months after surgery, statistically significant improvements were observed in the SRS-2 domains of Social Awareness (8 points, 95% CI 2-13, P = .03) and Social Motivation (7 points, 95% CI 2-15, P = .03). Total SRS-2 T-score improved in a clinically important manner for 56% (10/18) of patients, but the median change was not statistically significant (5 points, 95% CI -1 to 9, P = .10). VSQOL showed statistically significant improvements in the domains of Functional Vision (40 points, 95% CI 7-73, P = .02) and Bothered by Eyes/Vision (23 points, 95% CI 3-45, P = .02). CONCLUSIONS: Refractive surgery led to clinically and statistically significant improvements in domains of social functioning and VSQOL at 12 months after surgery. A narrow majority of patients demonstrated a clinically important improvement in overall social functioning, but these changes were not statistically significant. The results suggest that refractive surgery in children with neurodevelopmental disorders, ametropia, and spectacle nonadherence may provide developmental and quality-of-life benefits. Larger, controlled studies are required to validate these findings.

Refractive surgery to correct visual impairments in 267 children with autism spectrum and related neuro-developmental disorders: improvements in vision and behavior.

Background: Children with autism spectrum disorder (ASD) may have impaired vision owing to high refractive errors and aversion to spectacles or contact lenses. Visual blurring is caused by near-sighted myopia, far-sighted hyperopia, or astigmatism in one or both eyes. Refractive surgery can restore sharp vision and eliminate the need for spectacles and contact lenses. Restoration of sharp vision may improve ASD behavior. We aimed to determine the refractive outcomes in this cohort using ophthalmic measures and behavioral and school performance alterations after refractive surgery by employing parent-proxy reports. Methods: This interventional, retrospective case series included data from 267 children with refractive errors and neurodevelopmental disorders (NDDs) diagnosed as ASD alone or NDD with ASD-like behaviors over a 15-year period. One of three refractive surgery methods was employed, with the choice of method uniquely tailored to the child's eye anatomy. Laser photorefractive keratectomy (PRK) was performed in 131 children, implantation of a phakic intraocular lens (pIOL) in 115 children, and removal of the crystalline lens and implantation of an intraocular lens (refractive lens exchange, RLE) in 21 children. All procedures were performed under brief general anesthesia, with the child returning home on the same day. Results: The median age at surgery was 10.9 years and the median follow-up period was 3.1 years. Pre-operative refractive errors ranged from a mean (standard deviation) +7.5 (0.09) D to -14.3 (4.8) D. Surgery corrected 87% of the children to normal focal length (± 1 D). Visual acuity improved an average of 0.6 logarithm of the minimum angle of resolution, the equivalent of 6 lines on a standard eye chart. Change in visual acuity was significant (all P < 0.01) between baseline and the most recent follow-up examination in each of subgroups. Change in spherical equivalent refractive error at 3, 12, 24, 36, 60, and > 60 months post-operatively were significant (all P < 0.01) between baseline and each follow-up visit in each of subgroups. Social interactions and ASD behaviors improved in 72% (192) of the treated children (P < 0.01). The incidence of sight-threatening complications was low. Conclusions: Refractive surgery improves both visual function and behavior in most children with ASD and major myopia, hyperopia, or astigmatism. The PRK, pIOL, and RLE procedures appear to be effective and reasonably safe methods for improving refractive error, visual acuity, and behavior in many ametropic children with ASD and ASD-like NDDs.

Inter-Ocular Fixation Instability of Amblyopia: Relationship to Visual Acuity, Strabismus, Nystagmus, Stereopsis, Vergence, and Age.

PURPOSE: Amblyopia damages visual sensory and ocular motor functions. One manifestation of the damage is abnormal fixational eye movements. Tiny fixation movements are normal; however, when these exceed a normal range, the behavior is labeled "fixation instability" (FI). Here we compare FI between normal and amblyopic subjects, and evaluate the relationship between FI and severity of amblyopia, strabismus angle, nystagmus, stereopsis, vergence, and subject age. METHODS: Fixation eye movements were recorded using infrared video-oculography from 47 controls (15.3 ± 12.2 years of age) and 104 amblyopic subjects (13.3 ± 11.2 years of age) during binocular and monocular viewing. FI and vergence instability were quantified as the bivariate contour ellipse area (BCEA). We also calculated the ratio of FI between the 2 eyes: right eye/left eye for controls, amblyopic eye/fellow eye for amblyopes. Multiple regression analysis evaluated how FI related to a range of visuo-motor measures. RESULTS: During binocular viewing, the FI of fellow and amblyopic eye, vergence instability, and inter-ocular FI ratios were least in anisometropic and most in mixed amblyopia (P < .05). Each correlated positively with the strabismus angle (P < .01). During monocular viewing, subjects with deeper amblyopia (P < .01) and larger strabismus angles (P < .05) had higher inter-ocular FI ratios. In all, 27% of anisometropic and >65% of strabismic/mixed amblyopes had nystagmus. Younger age and nystagmus increased FI and vergence instability (P < .05) but did not affect the inter-ocular FI ratios (P > .05). CONCLUSIONS: Quantitative recording of perturbed eye movements in children reveal a major functional deficit linked to amblyopia. Imprecise fixation, measured as inter-ocular FI ratios, may be used as a robust marker for amblyopia and strabismus severity. NOTE: Publication of this article is sponsored by the American Ophthalmological Society.

Human deprivation amblyopia: treatment insights from animal models.

Amblyopia is a common visual impairment that develops during the early years of postnatal life. It emerges as a sequela to eye misalignment, an imbalanced refractive state, or obstruction to form vision. All of these conditions prevent normal vision and derail the typical development of neural connections within the visual system. Among the subtypes of amblyopia, the most debilitating and recalcitrant to treatment is deprivation amblyopia. Nevertheless, human studies focused on advancing the standard of care for amblyopia have largely avoided recruitment of patients with this rare but severe impairment subtype. In this review, we delineate characteristics of deprivation amblyopia and underscore the critical need for new and more effective therapy. Animal models offer a unique opportunity to address this unmet need by enabling the development of unconventional and potent amblyopia therapies that cannot be pioneered in humans. Insights derived from studies using animal models are discussed as potential therapeutic innovations for the remediation of deprivation amblyopia. Retinal inactivation is highlighted as an emerging therapy that exhibits efficacy against the effects of monocular deprivation at ages when conventional therapy is ineffective, and recovery occurs without apparent detriment to the treated eye.

A Prospective Evaluation of Infant Cerebellar-Cerebral Functional Connectivity in Relation to Behavioral Development in Autism Spectrum Disorder.

Background: Autism spectrum disorder (ASD) is a neurodevelopmental disorder diagnosed based on social impairment, restricted interests, and repetitive behaviors. Contemporary theories posit that cerebellar pathology contributes causally to ASD by disrupting error-based learning (EBL) during infancy. The present study represents the first test of this theory in a prospective infant sample, with potential implications for ASD detection. Methods: Data from the Infant Brain Imaging Study (n = 94, 68 male) were used to examine 6-month cerebellar functional connectivity magnetic resonance imaging in relation to later (12/24-month) ASD-associated behaviors and outcomes. Hypothesis-driven univariate analyses and machine learning-based predictive tests examined cerebellar-frontoparietal network (FPN; subserves error signaling in support of EBL) and cerebellar-default mode network (DMN; broadly implicated in ASD) connections. Cerebellar-FPN functional connectivity was used as a proxy for EBL, and cerebellar-DMN functional connectivity provided a comparative foil. Data-driven functional connectivity magnetic resonance imaging enrichment examined brain-wide behavioral associations, with post hoc tests of cerebellar connections. Results: Cerebellar-FPN and cerebellar-DMN connections did not demonstrate associations with ASD. Functional connectivity magnetic resonance imaging enrichment identified 6-month correlates of later ASD-associated behaviors in networks of a priori interest (FPN, DMN), as well as in cingulo-opercular (also implicated in error signaling) and medial visual networks. Post hoc tests did not suggest a role for cerebellar connections. Conclusions: We failed to identify cerebellar functional connectivity-based contributions to ASD. However, we observed prospective correlates of ASD-associated behaviors in networks that support EBL. Future studies may replicate and extend network-level positive results, and tests of the cerebellum may investigate brain-behavior associations at different developmental stages and/or using different neuroimaging modalities.

Impact of Ocular Conditions and Improvements After Refractive Surgery in Quality of Life for Children With Neurodevelopmental Disorders.

PURPOSE: This study aims to characterize the eye-related quality of life of children with neurodevelopmental and ocular disorders at baseline and after refractive surgery. DESIGN: Prospective interventional case series. METHODS: We enrolled children and adolescents 5 to 18 of age with neurodevelopmental disorders undergoing refractive surgery (6 for pre-/postsurgical assessment and 14 for baseline analysis). Eye-related quality of life was measured using the Pediatric Eye Questionnaire (PedEyeQ). Baseline levels of adaptive functioning and social behaviors were measured using the Adaptive Behavioral Assessment System (ABAS-3) and Social Responsiveness Scale (SRS-2). We assessed the correlation between baseline PedEyeQ scores, number of ocular comorbidities, magnitude of refractive error, and ABAS-3 and SRS-2 scores. RESULTS: At baseline, 14 patients demonstrated decreased median eye-related quality of life (<60/100) in 5 of 9 PedEyeQ domains, moderate deficiencies in social behaviors (SRS-2 median 71, range 49-90), and low adaptive functioning (ABAS-3 median percentile for age of 0.100). Baseline PedEyeQ scores did not correlate with magnitude of refractive error or adaptive functioning scores but did correlate with number of ocular comorbidities and social behavior scores. Six patients have undergone refractive surgery without complication. Postoperatively, 11 of 11 eyes were within ±1.5 diopters spherical equivalent. Four of 6 patients exhibited clinically significant improvements in PedEyeQ scores after surgery. CONCLUSIONS: Even in the presence of significant social and adaptive impairments, quality of life in children with neurodevelopmental disorders is decreased by ocular disorders. Refractive surgery is associated with clinically significant improvements in eye-related quality of life.

Refractive Surgery for Special-Needs Children with High Myopia.

Refractive surgery is useful in children with high isoametropic or anisometropic myopia who are aversive to spectacles or contact lenses. The majority have a neurodevelopmental disorder and the equivalent of legal blindness before surgery. Correction of myopia < 6 Diopters (D) is achieved by photorefractive keratectomy (PRK). Those with myopia > 6 D benefit from phakic IOL implantation, clear lens extraction (CLE), or refractive lens exchange (RLE). The rate of adverse events is low.

Longitudinal Changes in Vision and Retinal Morphology in Wolfram Syndrome.

PURPOSE: To report long-term ophthalmic findings in Wolfram syndrome, including rates of visual decline, macular thinning, retinal nerve fiber layer (RNFL) thinning, and outer plexiform layer (OPL) lamination. DESIGN: Single-center, cohort study. METHODS: A total of 38 participants were studied, who underwent a complete ophthalmic examination as well as optical coherence tomography imaging of the macula and nerve on an annual basis. Linear mixed-effects models for longitudinal data were used to examine both fixed and random effects related to visual acuity and optic nerve quadrants of RNFL and macula thickness. RESULTS: Participants completed a mean of 6.44 years of follow-up (range 2-10 years). Visual acuity declined over time in all participants, with a mean slope of 0.059 logMAR/y (95% CI = 0.07-0.05 logMAR/y), although nearly 25% of participants experienced more rapid visual decline. RNFL thickness decreased in superior, inferior, and nasal quadrants (ß = -0.5 µm/y, -0.98 µm/y, -0.28 µm/y, respectively). OPL lamination was noted in 3 study participants, 2 of whom had autosomal dominant mutations. CONCLUSIONS: Our study describes the longest and largest natural history study of visual acuity decline and retinal morphometry in Wolfram syndrome to date. Results suggest that there are slower and faster progressing subgroups and that OPL lamination is present in some individuals with this disease.

Prevalence of the Infantile Strabismus Complex in Premature Children With and Without Periventricular Leukomalacia.

PURPOSE: To determine whether rates of strabismus and associated visuomotor deficits differed among children with different severities of periventricular leukomalacia (PVL). DESIGN: Retrospective, case-control study. METHODS: Brain magnetic resonance images (MRI) obtained from 98 children aged ≥2 years were analyzed using a standardized scoring system: 67 of 98 had PVL (mean GA 31 weeks) and 31 of 98 did not have PVL (mean GA 29 weeks). Severity of PVL was scored as degree of damage to the posterior optic radiations and the splenium of the corpus callosum on MRI. Ophthalmologic examination data were collated to assess the prevalence of visuomotor deficits and the relationship to PVL severity (grades 1-3, mild to severe). RESULTS: Infantile strabismus was documented in 61% of children with mild, 74% with moderate, and 88% with severe PVL (esotropia: exotropia ratio 3.5:1). Associated ocular motor deficits also increased systematically with PVL severity: latent ("fusion maldevelopment") nystagmus (20%, 47%, and 40%, respectively), dissociated vertical deviation (13%, 28%, and 30%), and nasotemporal pursuit/optokinetic nystagmus asymmetry (23%, 38%, and 54%). Additionally, the prevalence of retrograde optic neuropathy increased with PVL severity (5%, 26%, and 38%). The prevalence of each of these signs was substantially lower in children who had no PVL. CONCLUSIONS: Children who suffer PVL are likely to develop the deficits of the infantile strabismus complex. The deficits tend to increase systematically as a function of PVL severity. These findings provide evidence that infantile strabismus is linked to perinatal damage to cerebral vergence and gaze pathways.

A phase Ib/IIa clinical trial of dantrolene sodium in patients with Wolfram syndrome.

BACKGROUNDWolfram syndrome is a rare ER disorder characterized by insulin-dependent diabetes mellitus, optic nerve atrophy, and progressive neurodegeneration. Although there is no treatment for Wolfram syndrome, preclinical studies in cell and rodent models suggest that therapeutic strategies targeting ER calcium homeostasis, including dantrolene sodium, may be beneficial.METHODSBased on results from preclinical studies on dantrolene sodium and ongoing longitudinal studies, we assembled what we believe is the first-ever clinical trial in pediatric and adult Wolfram syndrome patients with an open-label phase Ib/IIa trial design. The primary objective was to assess the safety and tolerability of dantrolene sodium in adult and pediatric Wolfram syndrome patients. Secondary objectives were to evaluate the efficacy of dantrolene sodium on residual pancreatic ß cell functions, visual acuity, quality-of-life measures related to vision, and neurological functions.RESULTSDantrolene sodium was well tolerated by Wolfram syndrome patients. Overall, ß cell functions were not significantly improved, but there was a significant correlation between baseline ß cell functions and change in ß cell responsiveness (R2, P = 0.004) after 6-month dantrolene therapy. Visual acuity and neurological functions were not improved by 6-month dantrolene sodium. Markers of inflammatory cytokines and oxidative stress, such as IFN-γ, IL-1ß, TNF-α, and isoprostane, were elevated in subjects.CONCLUSIONThis study justifies further investigation into using dantrolene sodium and other small molecules targeting the ER for treatment of Wolfram syndrome.TRIAL REGISTRATIONClinicalTrials.gov identifier NCT02829268FUNDINGNIH/National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) (DK112921, DK113487, DK020579), NIH/National Center for Advancing Translational Sciences (NCATS) (TR002065, TR000448), NIH training grant (F30DK111070), Silberman Fund, Ellie White Foundation, Snow Foundation, Unravel Wolfram Syndrome Fund, Stowe Fund, Eye Hope Foundation, Feiock Fund, Washington University Institute of Clinical and Translational Sciences grant UL1TR002345 from NIH/NCATS, Bursky Center for Human Immunology & Immunotherapy Programs.

A simple pars plana technique for iris enclavation of Artisan-Ophtec aphakic intraocular lenses.

The Artisan-Ophtec aphakic iris-enclaved anterior chamber intraocular lens (IOL) has been used to advantage in children and adults who lack capsular support for implantation of a standard posterior chamber IOL. However, even the most skilled anterior segment surgeon may encounter difficulties enclaving the IOL to the iris using the enclavation needle. We describe a simple, secure, rapid alternative method for enclaving the IOL that requires only two eye incisions: one at the corneal limbus and the other through the pars plana.

Safety of phakic intraocular collamer lens implantation in 95 highly myopic special-needs children.

PURPOSE: To assess the safety of intraocular collamer lens (ICL) implantation in children with high ametropia by reporting rates and case specifics of perioperative and longer-term adverse events (AEs).. SETTING: St. Louis Children's Hospital at Washington University Medical Center, St. Louis, Missouri. DESIGN: Retrospective case series. METHODS: Clinical data were collated retrospectively for 95 special-needs children (160 eyes) implanted with a Visian ICL over the past 5 years. All surgeries were performed at St Louis Children's Hospital under brief general anesthesia. The mean follow-up period was 2.0 ± 1.4 years (range, 0.5 to 5.2). RESULTS: The mean age at implantation was 9.3 ± 5.2 years (range, 1.8 to 25) and mean preoperative spherical equivalent refractive error was -11.20 ± 3.90 diopters (range, 4 to 22). 62 children (62/95, 65%) had a neurodevelopmental disorder. 3 eyes (3/160, 2%) reported minor AE, consisting of steroid-response ocular hypertension, which resolved with cessation of topical steroid drops. Endothelial cell loss averaged 8.1% over 2 years, comparable with that reported in ICL-implanted adults. The most common major AE (7 eyes [7/160, 4%]) was postoperative pupillary block, requiring revision of the peripheral iridotomy. 1 child (1 eye [1/160, 0.6%]) with self-injurious behavior required repair of a wound leak. 1 child (1 eye [1/160, 0.6%]) with Down syndrome developed a cataract 2.8 years after ICL surgery, and 1 child (1 eye [1/160, 0.6%]) with severe autism spectrum disorder experienced traumatic retinal detachment 1.2 years after implantation. CONCLUSIONS: The most common major AE among the cohort with Visian ICL was pupillary block due to closure of the iridotomy. Overall, the AE rate was low in this higher risk, difficult-to-manage population of special-needs children.

Visual acuity, refractive error, and regression outcomes in 169 children with high myopia who were implanted with Ophtec-Artisan or Visian phakic IOLs.

PURPOSE: To analyze outcomes in a large cohort of spectacle-aversive children with high myopia who were treated by implantation of the Ophtec-Artisan or Visian phakic intraocular lens (pIOL). METHODS: Outcome data were collated retrospectively in 78 children (115 eyes) implanted with the Ophtec-Artisan iris-enclaved anterior chamber pIOL and 91 children (154 eyes) implanted with the Visian ICL (intraocular collamer lens) sulcus pIOL. All children had difficulties with spectacle or contact lens wear. Mean age at surgery was 9.9 years; mean follow-up was 3.9 years (range, 0.6-14.1 years). RESULTS: A total of 248 of 269 eyes (92%) were corrected to within ± 0.5 D of their target value. Spherical correction averaged 12.3 ± 1.0 D. Refractive spherical regression was -0.04 D/year at last follow-up. Uncorrected distance visual acuity improved from an average logMAR 1.8 to 0.4; corrected distance visual acuity improved an average 0.3 logMAR. Of the treated children, 68% had a gain in binocular fusion. Neurobehavioral and/or visuomotor comorbidities were present in 87% of children. Five eyes (2%) developed retinal detachment an average 6 years after implantation. Nine eyes (3%) implanted with the Ophtec-Artisan pIOL required repositioning after trauma. CONCLUSIONS: Implantation of pIOLs in children is an effective method for correcting high myopia in spectacle noncompliant children. Rates of myopic regression after pIOL surgery are substantially lower than those reported for children treated by excimer laser photorefractive keratectomy (PRK). The prevalence of major complications was relatively low in this high-risk population.

Concern of Photosensitive Seizures Evoked by 3D Video Displays or Virtual Reality Headsets in Children: Current Perspective.

This review assesses the risk of a photic-induced seizure in a child during viewing of 3D (binocular 3 dimensional, stereoscopic) movies or games, either on standard video displays or when wearing a virtual reality (VR) headset. Studies published by pediatric epilepsy experts emphasize the low risk of 3D viewing even for children with known photosensitive epilepsy (PSE). The low incidence of PSE is noteworthy because the number of hours devoted to 2D or 3D screen viewing and/or VR headset use by children worldwide has increased markedly over the last decade. The medical literature does not support the notion that VR headset use poses a risk for PSE.

Effects of Immersive Virtual Reality Headset Viewing on Young Children: Visuomotor Function, Postural Stability, and Motion Sickness.

PURPOSE: To assess the safety of VR 3D headset (virtual reality 3-dimensional binocular-stereoscopic near-eye display) use in young children. Product safety warnings that accompany VR headsets ban their use in children under age 13 years. DESIGN: Prospective, interventional, before-and-after study. METHODS: Recordings were obtained in 50 children (29 boys) aged 4-10 years (mean 7.2 ± 1.8 years). Minimum binocular corrected distance visual acuity (CDVA) was 20/50 (logarithm of the minimum angle of resolution [logMAR] 0.4) and stereoacuity 800 seconds of an arc or better. A Sony PlayStation VR headset was worn for 2 sequential play sessions (of 30 minutes each) of a first-person 3D flying game (Eagle Flight) requiring head movement to control flight direction (pitch, yaw, and roll axes). Baseline testing preceded VR exposure, and each VR session was followed by post-VR testing of binocular CDVA, refractive error, binocular eye alignment (strabismus), stereoacuity, and postural stability (imbalance). Visually induced motion sickness was probed using the Simulator Sickness Questionnaire modified for pediatric use (Peds SSQ). Visual-vestibulo-ocular reflex (V-VOR) adaptation was also tested pre- vs post-trial in 5 of the children. Safety was gauged as a decline or change from baseline in any visuomotor measure. RESULTS: Forty-six of 50 children (94%) completed both VR play sessions with no significant change from baseline in measures of binocular CDVA (P = .89), refractive error (P = .36), binocular eye alignment (P = .90), or stereoacuity (P = .45). Postural stability degraded an average 9% from baseline after 60 minutes of VR exposure (P = .06). Peds SSQ scores increased a mean 4.7%-comparing pretrial to post-trial-for each of 4 symptom categories: eye discomfort (P = .02), head/neck discomfort (P = .03), fatigue (P = .03), and motion sickness (P = .01). None of the children who finished both trial sessions (94%) asked to end the play, and the majority were disappointed when play was halted. V-VOR gain remained unaltered in the 5 children tested. Three children (6% of participants) discontinued the trial during the first 10 minutes of the first session of VR play, 2 girls (aged 5 and 6 years) and 1 boy (aged 7 years). The girls reported discomfort consistent with mild motion sickness; the boy said he was bored and the headset was uncomfortable. No child manifested aftereffects ("flashbacks") in the days following the VR exposure. CONCLUSION: Young children tolerate fully immersive 3D virtual reality game play without noteworthy effects on visuomotor functions. VR play did not induce significant post-VR postural instability or maladaption of the vestibulo-ocular reflex. The prevalence of discomfort and aftereffects may be less than that reported for adults.

Successful treatment of an exudative choroidal hemangioma with oral propranolol in a 10-year-old boy.

A 10-year-old boy was referred for a circumscribed choroidal hemangioma with underlying exudative detachment of the left eye. To avoid general anesthetics required for laser-based therapy in a child, we began a trial of oral propranolol. The patient's exudative detachment resolved, with resulting improvement in visual acuity, and remained quiescent for 3 years.

Visual pathway function and structure in Wolfram syndrome: patient age, variation and progression.

BACKGROUND/AIMS: To report alterations in visual acuity and visual pathway structure over an interval of 1-3 years in a cohort of children, adolescents and young adults who have Wolfram syndrome (WFS) and to describe the range of disease severity evident in patients with WFS whose ages differed by as much as 20 years at first examination. METHODS: Annual, prospective ophthalmological examinations were performed in conjunction with retinal nerve fibre layer (RNFL) analysis. Diffusion tensor MRI-derived fractional anisotropy was used to assess the microstructural integrity of the optic radiations (OR FA). RESULTS: Mean age of the 23 patients with WFS in the study was 13.8 years (range 5-25 years). Mean log minimum angle resolution visual acuity was 0.66 (20/91). RNFL thickness was subnormal in even the youngest patients with WFS. Average RNFL thickness in patients with WFS was 57±8 µ or ~40% thinner than that measured in normal (94±10 µ) children and adolescents (P<0.01). Lower OR FA correlated with worse visual acuity (P=0.006). Subsequent examinations showed declines (P<0.05) in visual acuity, RNFL thickness and OR FA at follow-up intervals of 12-36 months. However, a wide range of disease severity was evident across ages: some of the youngest patients at their first examination had deficits more severe than the oldest patients. CONCLUSION: The genetic mutation of WFS causes damage to both pregeniculate and postgeniculate regions of the visual pathway. The damage is progressive. The decline in visual pathway structure is accompanied by declines of visual function. Disease severity differs widely in individual patients and cannot be predicted from their age.