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Background: To ascertain which countries in the world have retinopathy of prematurity (ROP) screening programmes and guidelines and how these were developed., Methods: An email database was created and requests were sent to ophthalmologists in 141 nations to complete an online survey on ROP screening in their country., Results: Representatives from 92/141 (65%) countries responded. 78/92 (85%) have existing ROP screening programmes, and 68/78 (88%) have defined screening criteria. Some countries have limited screening and those areas which have no screening or for which there is inadequate knowledge are mainly Southeast Asia, Africa and some former Soviet states., Discussion: With the increasing survival of premature babies in lower-middle-income and low-income countries, it is important to ensure that adequate ROP screening and treatment is in place. This information will help organisations focus their resources on those areas most in need., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Background: Intermittent exotropia is the most common form of divergent strabismus (squint) in children. Evidence regarding its optimum management is limited. A pilot randomised controlled trial has recently been completed (Surgery versus Active Monitoring in Intermittent Exotropia trial) to determine the feasibility of a full randomised controlled trial., Purpose: To identify drivers for and barriers against parents' participation in Surgery versus Active Monitoring in Intermittent Exotropia and to seek their views on information received, the need for randomisation, and enhancing acceptability., Methods: Multiple method qualitative study using semi-structured telephone interviews to explore parents' motivations and trial screening logs to provide an indication of common barriers. Exploratory thematic analysis identified key themes., Results: A total of 48 interviews were conducted (14 participants; 34 non-participants). Barriers included no desire for surgery/preference to 'wait and see', wanting surgery immediately, feeling uncomfortable about 'surrendering control' over decision-making/being managed 'at random', lack of confidence in the effectiveness of surgery, believing the risks outweighed the benefits, and lack of trust. Drivers included desiring surgery, 'nothing to lose', benefits offsetting the risks, and being in a trial would result in better care. Some also mentioned 'doing their bit' for research. Suggestions for enhancing acceptability included allowing choice of treatment group, giving more time for decision-making, expanding on information given, and improving communication. Many felt the necessity of randomisation was adequately explained, but there was some indication that it was misunderstood. Information extracted from the screening logs of 80/89 eligible non-participants indicated the most prevalent barrier was not wanting surgery/preferring to observe (56%), followed by desiring surgery straightaway (15%). Opposition to randomisation/wanting to retain control was recorded in 9% of cases as was the belief that the child's squint was not severe enough to warrant surgery., Limitations: Interviews were not audio-recorded. Not all who consented to interview could be contacted, although the response/contact rate was good (48/62). A few parents did not provide reasons for refusing the trial., Conclusion: Opposition to surgery and concerns about surrendering control were common obstacles to participation, whereas parents keen for their child to undergo the operation but happy to defer tended to embrace a 'nothing to lose' attitude. Many non-participants would have consented if allowed to choose group, although most of these would have chosen observation. While most parents felt happy with information given and that randomisation was adequately explained, it is of concern that there may be some misunderstanding, which should be addressed in any trial. These findings will inform future trials in childhood exotropia, for example, consideration of preference arms and improving communication. Lessons learnt from the Surgery versus Active Monitoring in Intermittent Exotropia trial could prove valuable to paediatric and surgical trials generally., (© The Author(s) 2015.)

Purpose: To examine factors contributing to eye-hand coordination deficits in children with amblyopia and impaired stereovision., Methods: Participants were 55 anisometropic or strabismic children aged 5.0 to 9.25 years with different degrees of amblyopia and abnormal binocularity, along with 28 age-matched visually-normal controls. Pilot data were obtained from four additional patients studied longitudinally at different treatment stages. Movements of the preferred hand were recorded using a 3D motion-capture system while subjects reached-to-precision grasp objects (two sizes, three locations) under binocular, dominant eye, and amblyopic/nonsighting eye conditions. Kinematic and "error" performance measures were quantified and compared by viewing condition and subject group using ANOVA, stepwise regression, and correlation analyses., Results: Movements of the younger amblyopes (age 5-6 years; n = 30) were much slower, particularly in the final approach to the objects, and contained more spatial errors in reaching (∼×1.25-1.75) and grasping (∼×1.75-2.25) under all three views (P < 0.05) than their age-matched controls (n = 13). Amblyopia severity was the main contributor to their slower movements with absent stereovision a secondary factor and the unique determinant of their increased error-rates. Older amblyopes (age 7-9 years; n = 25) spent longer contacting the objects before lifting them (P = 0.015) compared with their matched controls (n = 15), with absence of stereovision still solely related to increases in reach and grasp errors, although these occurred less frequently than in younger patients. Pilot prospective data supported these findings by showing positive treatment-related associations between improved stereovision and reach-to-grasp performance., Conclusions: Strategies that children with amblyopia and abnormal binocularity use for reach-to-precision grasping change with age, from emphasis on visual feedback during the "in-flight" approach at ages 5 to 6 years to more reliance on tactile/kinesthetic feedback from object contact at ages 7 to 9 years. However, recovery of binocularity confers increasing benefits for eye-hand coordination speed and accuracy with age, and is a better predictor of these fundamental performance measures than the degree of visual acuity loss., (Copyright 2014 The Association for Research in Vision and Ophthalmology, Inc.)

Background: Primary ciliary dyskinesia (PCD) is a rare, genetically heterogeneous ciliopathy disorder affecting cilia and sperm motility. A range of ultrastructural defects of the axoneme underlie the disease, which is characterised by chronic respiratory symptoms and obstructive lung disease, infertility and body axis laterality defects. We applied a next-generation sequencing approach to identify the gene responsible for this phenotype in two consanguineous families., Methods and Results: Data from whole-exome sequencing in a consanguineous Turkish family, and whole-genome sequencing in the obligate carrier parents of a consanguineous Pakistani family was combined to identify homozygous loss-of-function mutations in ARMC4, segregating in all five affected individuals from both families. Both families carried nonsense mutations within the highly conserved armadillo repeat region of ARMC4: c.2675C>A; pSer892* and c.1972G>T; p.Glu658*. A deficiency of ARMC4 protein was seen in patient's respiratory cilia accompanied by loss of the distal outer dynein arm motors responsible for generating ciliary beating, giving rise to cilia immotility. ARMC4 gene expression is upregulated during ciliogenesis, and we found a predicted interaction with the outer dynein arm protein DNAI2, mutations in which also cause PCD., Conclusions: We report the first use of whole-genome sequencing to identify gene mutations causing PCD. Loss-of-function mutations in ARMC4 cause PCD with situs inversus and cilia immotility, associated with a loss of the distal outer (but not inner) dynein arms. This addition of ARMC4 to the list of genes associated with ciliary outer dynein arm defects expands our understanding of the complexities of PCD genetics.

Purpose: During development, the presence of strabismus and anisometropia frequently leads to amblyopia, a visual disorder characterized by interocular acuity differences. Although additional deficits in contrast sensitivity, crowding (the impaired recognition of closely spaced objects), and stereoacuity are common, the relationship between these abilities is unclear., Methods: We measured the covariation between these four abilities in children 4 to 9 years of age (n = 72) with strabismus, anisometropia, or mixed strabismus/anisometropia, and unaffected controls. Children reported the orientation of a target (a modified "Pac-Man," similar to Landolt-C stimuli) using four "ghosts" as references. Using a modified staircase procedure we measured threshold size (acuity), contrast detection, foveal crowding (the minimum separation between target and ghost-flankers supporting accurate identification), and stereoacuity (with random-dot stereogram ghosts)., Results: Group averages revealed significant interocular differences (IODs) in acuity for all three clinical groups (0.2-0.3 log minutes), and significant crowding IODs for the strabismic and mixed groups (0.6 and 0.4°, respectively). Nonetheless, crowding IODs were correlated with acuity IODs in all four groups (r values between 0.43 and 0.59 and P < 0.05; P = 0.07 in the mixed group). Similarly, the occurrence of stereo-blindness (most common in strabismic and mixed groups) was associated with a significant increase in IODs for both acuity and crowding (each P < 0.05). No correlations were found with contrast detection., Conclusions: Our results demonstrate an association between IODs in acuity and crowding and, furthermore, between these IODs and the presence of stereo-vision. We suggest that the deficits derived from strabismus and anisometropia lay along a continuum with abilities observed during normal development.

Purpose: To describe surgical outcomes in intermittent exotropia (X(T)), and to relate these to preoperative and surgical characteristics., Methods: 87 children (aged <11 years) underwent surgery in 18 UK centres; review data (mean 21 months post-surgery) were available for 72. The primary outcome measure was motor/sensory outcome (angle and stereoacuity). The secondary outcome measure was satisfactory control assessed by Newcastle Control Score (NCS)., Results: 35% of patients had excellent, 28% had fair and 37% had poor primary outcome. Preoperative and surgical characteristics did not influence primary outcome. Satisfactory control was achieved in 65% of patients, while X(T) remained/recurred in 20%. Persistent over-correction occurred in 15% of children. There was no relationship between over-correction and preoperative characteristics or surgical dose/type. Median angle improved by 12 prism dioptres (PD) at near and 19 PD at distance (p<0.001). Median NCS improved by 5 (p<0.001). 40% of those initially over-corrected remained so by last postoperative assessment; no relationship was found between an initial over-correction and good outcome., Conclusions: Whilst excellent motor/sensory outcome was achieved in one-third and satisfactory control in two-thirds of patients, the 37% poor outcome and 15% persistent over-correction rate is of concern. Surgical dose was similar in those under- and over-corrected, suggesting that over-corrections cannot be avoided merely by getting the dosage right: a randomised controlled trial (RCT) would shed light on this issue. Initial over-correction did not improve the chance of a good outcome, supporting the growing literature on this topic and further highlighting the need for randomised controlled trials of X(T) surgery.

Purpose: To investigate whether binocular information provides benefits for programming and guidance of reach-to-grasp movements in normal children and whether these eye-hand coordination skills are impaired in children with amblyopia and abnormal binocularity., Methods: Reach-to-grasp performance of the preferred hand in binocular versus monocular (dominant or nondominant eye occluded) conditions to different objects (two sizes, three locations, and two to three repetitions) was quantified by using a 3D motion-capture system. The participants were 36 children (age, 5-11 years) and 11 adults who were normally sighted and 21 children (age, 4-8 years) who had strabismus and/or anisometropia. Movement kinematics and error rates were compared for each viewing condition within and between subject groups., Results: The youngest control subjects used a mainly programmed (ballistic) strategy and collided with the objects more often when viewing with only one eye, while older children progressively incorporated visual feedback to guide their reach and, eventually, their grasp, resulting in binocular advantages for both movement components resembling those of adult performance. Amblyopic children were the worst performers under all viewing conditions, even when using the dominant eye. They spent almost twice as long in the final approach to the objects and made many (1.5-3 times) more errors in reach direction and grip positioning than their normal counterparts, these impairments being most marked in those with the poorest binocularity, regardless of the severity or cause of their amblyopia., Conclusions: The importance of binocular vision for eye-hand coordination normally increases with age and use of online movement guidance. Restoring binocularity in children with amblyopia may improve their poor hand action control.

A 44-year-old female teacher with partial third (oculomotor) nerve palsy had a small central field of binocular single vision (BSV) following three strabismus procedures. Over several years her field of BSV constricted further, coincident with the development of myopia in one eye secondary to early lens change and in the presence of significant astigmatism. Following bilateral lens extraction with toric intraocular lens implants, her field of BSV reexpanded., (Copyright © 2010 American Association for Pediatric Ophthalmology and Strabismus. Published by Mosby, Inc. All rights reserved.)

Objective: To examine the effect of a unilateral epiretinal membrane (uERM) on visual acuity, stereopsis, and motor fusion in patients before and after successful surgery to remove the membrane., Design: Cohort study., Participants: Twenty-seven consecutive patients undergoing surgery to remove an idiopathic uERM and 30 normal control subjects., Methods: Patients underwent full orthoptic examination before and between 3 and 6 months after surgery to remove a uERM. Stereoacuities were analyzed statistically using the Wilcoxon signed-rank test, Mann-Whitney U test, and Spearman correlation. Motor fusion ranges and visual acuities were compared using paired and unpaired t tests, with correlations examined by linear regression., Main Outcome Measures: Snellen visual acuity, TNO (stereoscopic acuity test of the Netherlands; Netherlands Organisation for Applied Scientific Research; Laméris Ootech BV, Nieuwegein, the Netherlands) and Titmus stereoacuity, motor fusion range., Results: Postoperative acuity and improvement in visual acuity after removal of a uERM were better in patients with a shorter duration of symptoms. Stereoacuity was substantially reduced in the presence of a uERM (TNO, P<0.001; Titmus, P<0.001; Mann-Whitney U test), as were total motor fusion ranges at near and distance (near P = 0.002; distance P = 0.015; t test). Stereoacuity was worse in patients with symptoms of longer duration (TNO, P = 0.21; Titmus, P = 0.045; Spearman rank correlation). After successful surgery, stereoscopic function improved. This improvement occurred mainly in those patients with better preoperative stereoacuity and a shorter duration of symptoms., Conclusions: Improvement in visual acuity after surgery was greater in patients with visual symptoms of shorter duration. A uERM adversely affected stereoscopic function, an effect that increased with time. The best monocular and binocular visual outcomes occurred in those patients who had earlier surgery.

Purpose: To examine changes in color- and motion-related visual function in patients with strabismic amblyopia., Methods: Motion-onset and color visual-evoked potentials (VEPs) were recorded in 16 adult patients with strabismic amblyopia which had an early onset, before 18 months of age, and 14 patients with amblyopia of later onset. The results are compared with those from 21 normal adults., Results: The peak times of motion-onset VEPs in the amblyopic eye were longer those than in the fellow eye in patients with both early- and late-onset strabismic amblyopia, but peak times in both amblyopic and fellow eyes were shorter than those in normal eyes. In patients with late- but not early-onset amblyopia, the peak times for color VEPs were significantly longer in amblyopic than in fellow and normal eyes., Conclusions: The patterns of abnormality for motion-onset and color VEPs in patients with strabismic amblyopia are different, probably indicating differential changes in function in magno- and parvocellular pathways. These abnormalities affect both the amblyopic and fellow eyes and are different in patients with an onset of amblyopia before or after 18 months of age.

Purpose: Studies in nonhuman primates show that monocular visual deprivation starting at different ages has different effects on cells in the parvocellular and magnocellular laminae of the lateral geniculate nucleus. The present study used color and luminance contrast sensitivity (CS) measurements to look for differences in parvocellular- and magnocellular-related visual function in human subjects with strabismic amblyopia., Methods: Fifteen subjects with early- and 14 with late-onset strabismic amblyopia and similar ranges of visual acuity were studied, together with 15 subjects with normal vision. Contrast sensitivities were measured to an equiluminant (L-M cone-modulated) grating with slow onset and an achromatic (L+M cone-modulated) 0.8-cpd grating with rapid onset using an adaptive, Results: Luminance and color CS were lower in the amblyopic eyes than in the fellow eyes of all amblyopes. For luminance CS, this was due both to an increase in sensitivity of the fellow eye and to a reduction in sensitivity in the amblyopic eye. Color CS was greatly reduced in the amblyopic and fellow eyes of subjects with strabismic amblyopia of early- and late onset compared with subjects with normal vision. The reduction in color CS compared with luminance CS was significantly greater in eyes with late- rather than early-onset amblyopia., Conclusions: Parvocellular and magnocellular function are differentially affected in the amblyopic and fellow eyes of subjects with strabismic amblyopia. The difference is more marked in late-onset amblyopia than in early-onset amblyopia.

The optic chiasm is one of the most popular models for studying axon guidance. Here axons make a key binary decision either to cross the midline to innervate the contralateral hemisphere or to remain uncrossed. In rodents, midline interactions between axons from the two eyes are critical for normal development, as early removal of one eye systematically disrupts hemispheric projections from the remaining eye, increasing the crossed projection at the expense of the uncrossed. This is similar to the abnormal decussation pattern seen in albinos. This pattern is markedly different in marsupials where early eye removal has no impact on projections from the remaining eye. These differences are related to the location of the uncrossed projection through the chiasm. In rodents these axons approach the midline whereas in marsupials they remain segregated laterally. We provide anatomical evidence in man suggesting that, unlike in rodents, uncrossed axons are confined laterally and do not mix in each hemi-chiasm, which is a pattern similar to that found in marsupials. Further, we demonstrate electrophysiologically, using visual cortical evoked potentials, that the failure of one eye to develop in man has no impact on the hemispheric projections from the remaining eye. These data demonstrate that the mechanisms regulating chiasmal development in man differ from those in rodents but may be similar to those in marsupials. We suggest that mouse models of the organization and development of the optic chiasm are not common to placental mammals in general.

Aim: To examine how stereoacuity changes with age as measured by a variety of stereotests., Methods: Stereoacuity has been measured in 60 normal subjects aged 17-83 years by a single observer using TNO, Titmus, Frisby near, and Frisby-Davis distance stereotests. Motor fusion was measured at (1/3) metre and 6 metres., Results: Overall stereoacuity measured by all tests showed a mild decline with age (p<0.001 for all tests; Spearman rank correlation). A marked reduction to screening or absent levels of stereoacuity was seen in five subjects aged over 55, but only with the TNO stereotest. All these subjects were able to achieve a stereoacuity of 200 seconds of arc or better with the Titmus test and 340 seconds of arc or better using the Frisby near stereotest. There was a small decline with age in the base out motor fusion range measured at 6 metres (p<0.05; Spearman rank correlation). No subject described difficulty in judging distances for everyday tasks., Conclusions: Although subjects showed some decline in stereoacuity with age by all tests, the large drop in stereoacuity seen in some older subjects using the TNO test was probably due to difficulty overcoming the dissociative effect of the test rather than a true reduction in cortical disparity detection. Results of random dot stereotests should be interpreted with caution in older patients, particularly with respect to their ability to perform everyday visual tasks.

A failure of human foveal development only occurs in two genetically determined conditions; aniridia (Pax6 mutation) and albinism (tyrosinase mutation). The chiasmatic pathways from this region are disrupted in albinism and central retinal blood vessel patterns are abnormal. It is assumed that these three abnormalities have a common mechanism. Here we investigate whether similar abnormalities are present in subjects with aniridia. Using fundus photographs it is shown that abnormal blood vessel patterns are present in aniridia, but these significantly differ from those in albinos. Using electrophysiological techniques, abnormal hemispheric projections through the chiasm are demonstrated in albinos, but aniridics do not differ from normal subjects. These results demonstrate that although mutations in Pax6 and tyrosinase both affect central retinal development, they have a fundamentally different impact on the formation of the retinal vasculature and the projections from this region. This strongly suggests that separate mechanisms regulate the development of the central retina and decussation patterns at the optic chiasm.

Aims: To examine the effect of a unilateral full thickness macular hole on sensory and motor binocular function and to study recovery after successful surgical closure., Methods: Twenty eight consecutive patients undergoing surgery for a unilateral macular hole underwent orthoptic examination, including measurements of Titmus and TNO stereoacuity and motor fusion range before surgery. Twenty three patients had successful anatomical closure. Fifteen of these patients, who had both improved acuity in the operated eye following surgery and were available for further testing, underwent repeat orthoptic assessment 2-7 months after surgery., Results: In all patients stereoacuity was reduced before surgery, but few patients were subjectively aware of a deficit of depth perception affecting their everyday life. In those patients with improved Snellen acuity after surgery, stereoacuity measured by the Titmus stereotest also improved significantly, but not that measured by the TNO test. Two patients were aware of a subjective improvement in depth perception. Motor fusion was markedly reduced compared to normal before surgery, with only limited recovery after surgery., Conclusion: A unilateral macular hole notably reduced both stereoacuity and motor fusion. Successful closure improved the deficit in stereoacuity associated with the hole when measured by a stereotest using contoured stimuli. The majority of patients were not subjectively aware of the deficit in stereoacuity or its improvement following surgery.

Purpose: To evaluate the contribution of electrodiagnostic testing (EDT) to the management of children in a paediatric ophthalmology service using the Greenwich Grading System (GGS)., Methods: A retrospective analysis was performed of the case notes of 105 of the 113 paediatric patients referred from the Strabismus and Paediatric Service at Moorfields Eye Hospital for electrophysiological testing over a 1-year period. The GGS was used to quantify the contribution of EDT to the diagnosis, overall investigation, and treatment of each patient. Patients were further subdivided into different diagnostic groups to allow comparison of the value of EDT in different conditions., Results: EDT was found to be of value in 91% of the children tested and was considered an essential investigation in 71%. EDT made a new diagnosis in 7% of patients, changed it in 5%, and confirmed or excluded a diagnosis in 79%. EDT made a useful contribution to the overall investigation of 89% of the patients and was considered the only test that could provide the required information in 71%. The results of EDT allowed reassurance and/or explanation with regard to the diagnosis, prognosis, and treatment in 91% of children. In one patient, treatment was changed as a result of EDT. The clinical outcome was not adversely affected in any patient., Conclusions: EDT was of value to the clinical management of most of the children reviewed, mainly by confirming or excluding a clinical diagnosis and allowing explanation and reassurance to children and parents. Electrodiagnostic information gave a new or changed diagnosis in 12% of the children.

A deficiency of melanin in the retinal pigment epithelium, which regulates the development of neural retina, leads to chiasmal misrouting such that the uncrossed pathway (to the ipsilateral hemisphere) is reduced relative to the crossed pathway (to the contralateral hemisphere). This study examines age-related changes in the flash and pattern appearance visual evoked potentials (VEP) of human albinos. Scalp recorded cortical VEPs to flash (FVEP) and pattern appearance stimulation were recorded in 58 albino (8 months to 60 years) and 34 normal subjects (4-55 years). VEPs were analysed by amplitude and latency. The contralateral hemisphere FVEP amplitude decreased with age in albino subjects, as in both hemispheres in normals. However, the ipsilateral hemisphere FVEP amplitude was significantly lower in young albino subjects, initially giving a marked interhemispheric asymmetry, but this normalized with age. Significant interhemispheric FVEP latency asymmetries were not observed. The contralateral pattern appearance VEP latency in albino subjects decreased with age, as in both hemispheres in normals; the ipsilateral latency increased significantly with age. Significant interhemispheric pattern appearance VEP amplitude asymmetries were not observed. These novel and unexpected observations indicate significant age-related changes in the retinocortical pathways of the human albino. These changes have implications for our understanding of development and plasticity of the central visual pathways.

Aim: To investigate the relation between the clinical and electrophysiological abnormalities of patients undergoing visual evoked potential investigation for albinism., Methods: 40 subjects with a probable or possible clinical diagnosis of albinism underwent pattern appearance and/or flash visual evoked potential (VEP) examination. The VEP findings are correlated with the clinical features of albinism determined by clinical examination and orthoptic assessment., Results: The majority of patients with clinical evidence of albinism showed a contralateral predominance in the VEPs. There was close correlation between the clinical signs of albinism and the degree of contralateral VEP predominance. This manifested as an interhemispheric latency asymmetry to monocular pattern appearance stimulation but amplitude asymmetry to flash stimulation. The strongest correlation for pattern appearance interhemispheric latency difference was with foveal hypoplasia (rho = 0.58; p = 0.0003) followed by nystagmus (rho = 0.48; p = 0.0027) and iris transillumination (rho = 0.33; p = 0.039). The VEP abnormalities were of greater magnitude in those patients with most features of albinism. Several patients with apparently mild disorders of ocular pigmentation had small but significantly abnormal VEP latency asymmetries., Conclusion: There is a strong association between the magnitude of the interhemispheric latency asymmetry of the pattern appearance VEP, and of amplitude asymmetry of the flash VEP, with the clinical signs of albinism. The data are consistent with a spectrum of abnormalities in albinism involving both clinical expression and electrophysiological misrouting, which is wider than previously recognised.

Purpose: To compare visual evoked potentials (VEPs) and contrast sensitivity in adults with early- or late-onset strabismic amblyopia., Methods: Twelve adults with early- and 12 with late-onset strabismic amblyopia with similar ranges of visual acuity were studied. Pattern-onset VEPs to 30-minute checks were recorded at a range of contrast levels. Contrast sensitivity (CS) was measured at 3.2 cyc/deg using a two-alternative, forced-choice staircase method., Results: There was no significant difference in VEP CII latency or amplitude between amblyopic and fellow eyes across all contrast levels for the early-onset group, but in the late-onset group, CII latencies were significantly longer and amplitudes smaller in the amblyopic eye. CII responses in both amblyopic and fellow eyes of the early-onset amblyopes were of significantly shorter latency and smaller amplitude than normal. In the late-onset group the CII responses from the amblyopic eye were of significantly increased latency and reduced amplitude compared with normal, whereas latency and amplitude of fellow eye responses did not differ significantly from normal. Late-onset amblyopes showed reduced CS across the central field for the amblyopic eye, but increased CS for the fellow eye compared with normal. In the early-onset group, central CS did not differ between amblyopic and fellow eyes or from normal., Conclusions: There are significant differences in the electrophysiological and psychophysical characteristics of adults with early- and late-onset strabismic amblyopia.

Purpose: To assess electrophysiological recovery in successfully treated strabismic amblyopes., Methods: Pattern reversal visual evoked potentials were recorded from 11 successfully treated strabismic amblyopes 7 to 11 years of age and 10 age-matched normal children using 12.5' and 50' checks., Results: Nine amblyopic eyes had recovered to a Snellen acuity of 6/6 or better, and the remaining 2 were 6/9 after patching. Comparison between the amblyopic and the fellow eyes showed significantly lower P100 amplitude for the amblyopic eyes with small checks (difference -16.7%; P <.02) and significantly longer latency with larger checks difference (+5.0%; P <.02). The P100 latencies to stimulation of both the amblyopic and fellow eyes by 12.5' checks were markedly longer than in normal subjects (amblyopic eye, +11.7%, P <.0001; fellow eye, +7.7% P <.002)., Conclusions: Successfully treated amblyopic eyes showed significantly longer latency than did normal eyes with small check stimulation. However, the nonamblyopic fellow eyes also showed significantly longer latency than did normal eyes, suggesting altered central processing.

Purpose: To quantify the effect of a fadenoperation to a vertical rectus muscle on the field of binocular single vision (BSV)., Patients and Methods: BSV was assessed quantitatively in 32 patients before and after a fadenoperation to a single vertical rectus muscle by measuring the vertical extent of single vision in the midline and a score for the total field of BSV. Patients were aged from 14 to 72 years. All patients had diplopia in either downgaze or upgaze before surgery. In 11 patients, this was due to a fourth cranial nerve palsy, and in 8 patients it followed an orbital floor fracture., Results: The 15 patients who had an inferior rectus fadenoperation alone showed a significant mean increase in downward and total vertical extent of BSV and in their field of BSV. The 9 patients who underwent a superior rectus fadenoperation alone showed a significant increase in total vertical extent of BSV and field of BSV score. Three of the 8 who underwent a fadenoperation combined with another strabismus procedure at the same time had a substantial improvement in their score, but after the other 5 showed little change. Patients with a paretic deficit showed substantially more improvement than those with an upgaze deficit after a blowout fracture., Conclusion: The fadenoperation to a vertical rectus muscle produced a significant functional expansion in the field of BSV in approximately two thirds of patients. The procedure was more effective in incomitant squints of paretic rather than mechanical etiology.

Purpose: To compare the binocular enhancement of contrast sensitivity and stereoacuity in patients with Duane syndrome and normal subjects., Methods: Monocular and binocular contrast sensitivity functions were determined using a two-alternative, forced-choice method in 14 patients with Duane syndrome and 14 normal subjects. Monocular and binocular log minimum angle of resolution (logMAR) acuities were measured, and stereoacuity was determined using the Titmus and TNO stereotests., Results: In the patients with Duane syndrome, the binocular enhancement of contrast sensitivity was increased across all spatial frequencies, although stereoacuity was reduced compared to that of the normal subjects. The increased enhancement was caused by a reduction in monocular contrast sensitivity rather than an increase in binocular contrast sensitivity. The patients with Duane syndrome also showed a generalized reduction of contrast sensitivity at high spatial frequencies., Conclusions: It is suggested that the combination of reduced stereoacuity and increased binocular enhancement of contrast sensitivity seen in Duane syndrome can be explained by a partial loss of binocular cortical cells, caused by intermittent misalignment of the eyes during early visual development.

Purpose: To study the effects that the abnormal eye movements of patients with Duane retraction syndrome have on the development of binocular function., Methods: Pattern reversal visual evoked responses (VEPs) to 15-minutes-of-arc and 60-minutes-of-arc checks and binocular beat VEPs to diffuse sinusoidally modulated 18- and 20-Hz stimuli were recorded in 10 patients with Duane retraction syndrome who maintain binocular function by using an abnormal head posture. Visual acuity, stereoacuity, and eye movements were measured. The results have been compared to those from 10 normal subjects., Results: The patients with Duane retraction syndrome had reduced stereoacuity compared to the normal control group (TNO mean, 82.5 seconds of arc compared to 37.5 seconds of arc; Titmus mean, 143 seconds of arc compared to 44 seconds of arc). The binocular beat VEPs showed a significantly reduced difference beat response at 2 Hz in the patients with Duane syndrome compared to normal subjects (mean signal-to-noise ratio 2.40 +/- 1.05 compared to 4.30 +/- 2.66; t = 2.21, df = 18, P < 0.05). Binocular enhancement of the P100 pattern reversal amplitude to 15-minute checks was increased in these patients, because of a reduction of the monocular P100 amplitudes compared to the normal group., Conclusions: Patients with Duane syndrome who maintain binocular function using an abnormal head posture have reduced stereoacuity and show electrophysiological evidence of reduced cortical binocular interaction.

Aims: To study binocular function in patients with longstanding asymmetric keratoconus., Methods: In 20 adult patients with longstanding asymmetric keratoconus managed with a scleral contact lens a full clinical and orthoptic assessment was performed with and without the scleral contact lens in the poorer eye., Results: All 20 patients had a corrected acuity of at least 6/9 in their better eye. With the scleral lens in situ the acuity of the poorer eye ranged from 6/6 to 6/60 and without the lens from 6/18 to hand movements. Patients were aged from 18 to 68 years and had worn a scleral contact lens for between 3 and 106 months. Without the contact lens in their poorer eye all patients had a small exotropia and all showed suppression, with the exception of one patient who had a right hypertropia with diplopia. With the scleral lens in situ 12 patients had an exophoria or esophoria, six a microexotropia, and two a manifest exotropia with suppression., Conclusions: Binocular function breaks down in some adult patients with longstanding asymmetric keratoconus. This is probably caused by longstanding unilateral visual deprivation. There are similarities to the breakdown of binocular function seen in some patients with a longstanding dense unilateral adult onset cataract who can develop intractable diplopia following cataract surgery.

Aim: To study the effects of supervised inpatient occlusion treatment for amblyopia in children who had failed to respond to outpatient treatment., Methods: A retrospective study of 39 children admitted to a paediatric ophthalmic ward for 5 days of supervised intensive occlusion therapy having previously failed to respond to outpatient occlusion. Visual acuity of amblyopic and fellow eyes was recorded at each clinic visit before admission, daily during admission, and at each outpatient visit after discharge., Results: There was no significant overall improvement in visual acuity during a mean of 9 months of attempted outpatient occlusion before admission. During the 5 days of admission 26 children (67%) gained at least one line of acuity in their amblyopic eye and five (13%) gained three or more lines (mean gain 1.03 Snellen lines). The acuities of both the amblyopic and fellow eyes subsequently improved with continuing part time patching as an outpatient, including in nine of the children who did not respond during admission. At the last recorded visit, at a median time of 14 months after discharge, 13 (33%) of the patients had an acuity of at least 6/12 in their amblyopic eye., Conclusions: The acuity of amblyopic eyes did not improve without effective treatment. Subsequent supervised inpatient occlusion therapy was effective in the majority of the children.

Purpose: To study the maturation of normal binocular vision., Methods: Binocular visual function has been studied and monocular and binocular pattern reversal visual-evoked potentials (VEP) recorded in 20 normal subjects aged 5 to 43 years., Results: Stereoacuity improved significantly between the age of 5 and adulthood. Mean stereoacuity for eight children measured by the Titmus test was 61 seconds of arc and 56 seconds of arc by the TNO test. For the 12 adults in the study, corresponding mean stereoacuities were 45 and 31 seconds of arc. Over the same timespan, binocular enhancement of the VEP P100 amplitude decreased. For the children aged 5 to 10 years, the mean binocular VEP enhancement to 20' checks was 1.60, whereas for young adults it was 1.19. There was no comparable change in the binocular enhancement to 40' checks, with mean binocular enhancement of 1.31 in the children and 1.26 in the young adults. Over the same age range, VEP latency also decreased., Conclusion: During visual maturation, improvement in stereoacuity is accompanied by a fall in binocular enhancement of the P100 amplitude of the VEP to small checks and a reduction in the P100 latency.

Purpose: To study the effect of monocular visual deprivation caused by dense unilateral cataracts in adults., Methods: Visual evoked potentials have been recorded in 11 patients after removal of a dense unilateral cataract acquired in adulthood. These were compared with those from 8 control patients after removal of a mild lens opacity., Results: Visual evoked potentials recorded on the first day after removal of a longstanding, dense, unilateral cataract showed a marked delay to stimulation of the operated eye compared to the unoperated eye. No delay was found in the operated or unoperated eye of control patients. Delays in the visual evoked potential returned to normal within approximately 3 months after surgery, with the exception of the two patients with the most longstanding cataracts in whom the delays persisted much longer., Conclusions: The adult central visual system is sensitive to visual deprivation caused by a longstanding, dense, unilateral cataract. The changes found may be important in understanding the causes of intractable diplopia, which sometimes occurs after the removal of such cataracts.

Monocular and binocular visual evoked potentials were recorded in eight patients with Duane's syndrome who used an abnormal head posture to maintain binocular single vision. With their abnormal head posture, all patients had stereoscopic vision, although with mildly reduced stereoacuity, and the visual evoked potential showed binocular enhancement (mean binocular to monocular ratio, 1.44). Without their head posture, the patients experienced diplopia or suppressed vision in one eye. Binocular visual evoked potentials recorded under these conditions were of lower amplitude (mean binocular to monocular ratio, 1.05). However, without the abnormal head posture, a manifest strabismus was present and the deviating eye was not fixating the stimulus screen. Monocular visual evoked potentials recorded with the eye fixating just to one side of the screen gave little or no response, and this lack of fixation may account for the loss of binocular enhancement of the visual evoked potential in strabismus.

Studies of the effect of visual deprivation on cells in the lateral geniculate nucleus (LGN) show that there are two distinct sensitive periods in the monkey during which different reactions between the visual pathways related to the two eyes predominate and requirements for recovery from deprivation differ. The first extends from birth to about 8 weeks of age. The main interaction between the pathways from the two eyes is competitive, segregation of cortical ocular dominance columns occurs during this early period and monocular deprivation results initially in hypertrophy of undeprived LGN cells, with later parallel shrinkage of both deprived and undeprived parvocellular cells. Simply reopening the closed eye produces no recovery but reverse suture is effective in reversing some of the changes. The second sensitive period starts from about 8 weeks of age, although the peak of the later sensitivity appears to be at 7-9 months of age and some effect is still present at 12-18 months. During this later phase a cooperative interaction between the pathways related to the two eyes is necessary for normal development and in the absence of this selective shrinkage of both deprived and undeprived parvocellular LGN cells occurs. Simply reopening an eye during this late sensitive period allows recovery of these cells to normal size.

The significance of lipid-containing cells found at autopsy in the white matter of infant brains is controversial, particularly with respect to their postulated role as markers of the "sudden infant death syndrome." To determine whether such cells are indicative of prior nonlethal hypoxic insult, we quantitated them in the brains of control infant monkeys and in two groups of infant monkeys that were subjected to 30 minutes of hypoxic insult. One group consisting of monkeys that died less than 48 hours after the hypoxia, and the other of those that survived 7 to 13 days following the insult. The quantification of lipid-containing cells was undertaken in frozen brain sections stained with Oil red O; sections of brains from 4 perfusion-fixed animals were evaluated by electron microscopy. Lipid-containing cells were found in the corpus callosum, in the septum, and in periventricular white matter in both posthypoxic and control animals. There was a relationship between numbers of lipid-containing cells and the age of the animal; animals with large numbers were less than 28 days old. Decreases in numbers of lipid-containing cells correlated with advancing myelination as well as with age. Electron microscopic evaluation revealed lipid droplets in the cytoplasm of cells with irregularly shaped nuclei, densely clumped chromatin, occasional microtubules, and narrow cytoplasmic processes. We suggest that lipid-containing cells in the white matter of the brains of infants are related to age and to maturational factors and, in the absence of other pathologic signs, are not related to prior hypoxic injury.

Three infant monkeys were monocularly deprived from birth and reverse sutured at 3 weeks of age for a further period of 1, 2 or 5 weeks before perfusion. Cell areas were measured in the lateral geniculate nuclei and compared to those in normal monkeys and in monkeys following monocular closure. One week after reverse suture, cells in the initially deprived parvocellular laminae were 17% larger than normal and those in the initially undeprived laminae were 28% larger than normal. The initially undeprived parvocellular cells then shrank back to 14% larger than normal at 2 and 5 weeks while the initially deprived cells also remained hypertrophied. Following reverse suture at 3 weeks of age cells in parvocellular LGN laminae related to both eyes are simultaneously hypertrophied until at least 8 weeks of age and the LGN is therefore markedly abnormal even though the size difference between initially deprived and undeprived cells has been cancelled.

Cell areas have been measured in the lateral geniculate nucleus following enucleation in 7 infant and 3 adult monkeys. Deafferented cells showed rapid transneuronal degeneration. Following enucleation at birth non-deafferented parvocellular LGN cells underwent hypertrophy which was followed by a delayed return to normal size. Enucleation at 7 months of age caused marked shrinkage of non-deafferented parvocellular cells. These changes in the non-deafferented cells are similar to those following monocular lid closure at the same ages. Sizes of non-deafferented cells were unchanged following enucleation of adult monkeys.

The intrinsic connections of area 4 of the monkey have been investigated with axonal degeneration methods after the placement of microelectrode lesions within the cortex. The fibre degeneration is restricted to within a few millimetres of the damage and is asymmetrically distributed in the form of an ellipse with its long axis anteroposteriorly. The same pattern is found in all topographic subdivisions of the motor cortex. There are two distinct zones of degeneration, dense fine terminal degeneration for 200 to 300 micrometer all around the lesion, and a moderate degree of fibre terminal degeneration for a further 2 to 3 mm. The intrinsic connections are disposed predominantly in a horizontal or oblique direction and within the laminae of origin, but there are fibres passing between adjoining laminae and between layers III and V and VI. Two horizontal plexuses of degenerating fibres are present, at the boundary layers II and III and at the level of the Betz cells, and these fibres arise within the cortex. The afferent and efferent fibres of the cortex are arranged strictly perpendicular to the surface. The extent and pattern of the intrinsic connections of area 4 are very similar to those of area 17 of the visual cortex.

Mean cell areas have been measured in the most posterior part of the lateral geniculate nucleus containing the representation of central retina in 8 normal monkeys (Macaca mulatta) and in 5 monkeys following monocular closure from birth. Comparisons with cell size changes at a more anterior level, where pericentral retina is represented, show that size changes of parvocellular cells at the posterior level are significantly less, being only between half and two-thirds of those more anteriorly. The undeprived cells undergo less initial hypertrophy than cells at a more anterior level and subsequently the deprived cells show less shrinkage. There is no comparable difference for magnocellular cells.

Following removal of the motor or sensorimotor cortex in infant monkeys the projections of the remaining motor or sensorimotor cortex have been studied after long-term survival to look for anomalous projections from these areas. The patterns of degeneration resulting from lesions of the remaining motor or sensorimotor cortex corresponded to those found in normal adult monkeys in the spinal cord, pontine nuclei, superior colliculus, parvocellular red nucleus, subthalamic nucleus and thalamus. Sparse degeneration was found in the magnocellular part of the contralateral red nucleus which has not been described in normal animals and there is also the possibility of an increase in the crossed corticostriate projection. Infant monkeys do not form anomalous projections comparable to those found in the rat following neonatal sensorimotor cortex lesions.

This study has examined the effects of monocular visual deprivation on cells in the lateral geniculate nucleus of the primate by comparing the sizes of cells in deprived and undeprived LGN laminae of experimental rhesus monkeys with those of cells in the corresponding laminae of normal animals. A number of conclusions may be drawn from this comparison: monocular visual deprivation has major effects on cells in the undeprived LGN laminae and these vary with age at closure; the initial effect of monocular closure from birth is to cause marked hypertrophy of undeprived parvocellular cells with little shrinkage of the deprived parvocellular cells, whereas late monocular closure (after 2 months of age) causes marked shrinkage of both undeprived and deprived parvocellular cells; following monocular closure at birth, the LGN abnormality continues to evolve until at least 3 months of age, with a marked parallel shrinkage affecting both deprived and undeprived parvocellular cells. The initial hypertrophy of the undeprived cells is reversed and the deprived cells become smaller than normal; cells in the monkey LGN are sensitive to visual deprivation until about 1 year of age, much later than previously thought. Visual experience, however, modifies this sensitivity so that the effects of monocular visual deprivation are both qualitatively and quantitatively different at different ages; there are important differences between the susceptibility of cells in the magnocellular and parvocellular laminae to visual deprivation; and actual shrinkage of cells to markedly below normal size occurs and the smaller size is not simply failure of growth.

Infant monkeys have been subjected to hypoxia with an arterial pO2 of 20-22 Torr for 30 min. Following perfusion 1-2 weeks later electron microscopy of the motor cortex shows a selective degeneration of axon terminals making symmetrical synapses and which probably arise from inhibitory GABAergic interneurons. It is suggested that this may be related to the development of epilepsy following hypoxia.

Comparisons of mean cell area in the lateral geniculate nucleus between normal and monocularly deprived Rhesus monkeys show that closure started in the first few days of life produces an initial hypertrophy of up to 25% affecting undeprived parvocellular cells. Hypertrophy is maximal at 4 weeks. Following this there is later shrinkage affecting both deprived and undeprived parvocellular cells so that ultimately undeprived parvocellular cells are about 10% smaller and deprived parvocellular cells about 35% smaller than corresponding cells in normal animals.

Following monocular closure shortly after birth the deprived eye of 4 rhesus monkeys was reopened at different times. Following long-term recovery, cells in the undeprived laminae of the lateral geniculate nucleus of these animals were of normal size and those in the deprived laminae were markedly shrunken. Comparisons with animals monocularly deprived for similar periods indicate, however, that in 3 of these animals the undeprived parvocellular cells would have been markedly hypertrophied at the time of reopening the deprived eye, and in two of the animals, little shrinkage of the deprived parvocellular cells would have occurred by this time. Both undeprived and deprived parvocellular cells have therefore undergone marked shrinkage after the deprived eye had been reopened. The parallel shrinkage of deprived and undeprived parvocellular cells which occurs following closure at birth thus appears to be a consequence of the initial abnormalities produced by monocular closure rather than a direct result of the continuing lack of visual input to one eye.

Dendro-dendritic synapses have been observed infrequently in the deep layers of the motor cortex. The presynaptic dendrites are of a varicose type and themselves receive a considerable density of synapses both of the asymmetric and symmetrical type. The ultrastructure of the dendro-dendritic synapse itself shows the typical arrangement of presynaptic and postsynaptic membrane densities, often with presynaptic dense projections, and the membrane specialization is of the symmetrical type. There is the usual cleft containing electron-dense material between the presynaptic and postsynaptic profiles. The synaptic vesicles occur in a small cluster confined to a region close to the presynaptic membrane specialization; some of the vesicles are flattened and were shown by tilt analysis to be of the discoid type. Two examples were found of reciprocal dendro-dendritic synapses, both components being of the symmetrical type. A single axon terminal may make a synapse on to both dendrites involved in a dendro-dendritic synapse.