Relationship among fMRI, contrast sensitivity and visual acuity.

The purpose of this study was to ascertain whether visual acuity or contrast sensitivity function (CSF) is proportional to visual cortical function based on fMRI volume and level of activation or Z-score. Forced choice procedures were utilized to measure the monocular log minimal angle of resolution (logMAR) visual acuity and CSF. The CSF data were collapsed into a single index by the use of weighted mean contrast sensitivity (WMCS), being defined as the mean of the products of each spatial frequency multiplied by its corresponding contrast sensitivity. fMRI data had been obtained with a 1.5 T GE Signa scanner with visual stimuli including 1.0 and 2.0 c/deg vertical sinusoidal gratings. Subjects consisted of eight normal adults and five amblyopic patients, with the amblyopic subjects added to gauge whether the outcome was due to a restricted range of scores or the small number of study participants. In normal subjects, the fMRI volume and level of activation exhibited no statistically significant correlation with visual acuity at P<0.05. Statistically significant correlations were obtained between WMCS and fMRI volume (R=0.765, P=0.027) and fMRI level of activation (R=0.645, P=0.007), with right eye stimulation using the 1.0 c/deg grating. On the whole, statistically significant correlations between WMCS and fMRI parameters were maintained when subject age was held constant and when data from the five amblyopic subjects were included to expand the range of values and increase the number of data sets for analysis. fMRI volume and Z-score were more closely associated with the CSF, as defined by WMCS, than visual acuity. The results suggest that the CSF reflects the underlying visual cortical cells responsible for fMRI volume and the level of activation.

Development of two stable oral suspensions of levodopa-carbidopa for children with amblyopia.

PURPOSE: To develop stable liquid dosage forms of levodopa-carbidopa for use in children with amblyopia. METHODS: Levodopa (100 mg) and carbidopa (25 mg) tablets were used to prepare the suspensions at 5 and 1.25 mg/mL, respectively. For each suspension, five bottles were stored at 25 degrees C and five at 4 degrees C. Three samples were taken from each bottle at 0, 7, 14, 28, 42, 56, 70, and 91 days (n=15). Levodopa-carbidopa concentrations for each sample were measured in duplicate by validated and stability-indicating high-performance liquid chromatographic method. RESULTS: The mean concentrations of levodopa-carbidopa in Ora Plus/Ora Sweet suspensions were 96% and 92% of the initial concentrations for 28 days at 25 degrees C, and 94% and 93% for 42 days at 4 degrees C. In the suspension containing ascorbic acid, the mean concentrations of levodopa-carbidopa were above 93% and 92% for 14 days at 25 degrees C, and 93% and 92% for 28 days at 4 degrees C. This liquid formulation was administered to 15 children (mean age: 5.6+/-1.4 years) with amblyopia. The number and type of adverse effects were similar in the levo-dopa-carbidopa versus placebo group. CONCLUSION: Levodopa-carbidopa in extemporaneous suspensions prepared in Ora Plus and Ora Sweet were stable for 28 days when stored at 25 degrees C and for 42 days at 4 degrees C. Our data suggest our liquid formulation may be used safely in children with amblyopia.

Occlusion and levodopa-carbidopa treatment for childhood amblyopia.

PURPOSE: The purpose of the current study was to compare the effects of levodopa-carbidopa with and without part-time occlusion on visual function in older amblyopic children. METHODS: Thirteen older amblyopic children were randomly assigned to receive or not receive part-time occlusion (3 h/day) combined with 7 weeks of oral dosing with levodopa-carbidopa (1.02 mg/0.25 mg/kg body weight three times daily). Visual acuity, contrast sensitivity, and fusion were measured at baseline; 1, 3, 5, and 7 weeks during the treatment regimen; and 4 weeks after termination of all treatment. At these same times health status was assessed with standard laboratory blood tests, physical examination, and subjective questionnaire. RESULTS: From baseline to the follow-up test trial, both groups improved in visual acuity in the amblyopic eyes (occlusion group 20/116 to 20/76, P < .001; no occlusion group 20/90 to 20/73, P < .01) and dominant eyes (occlusion group 20/18 to 20/15, P > .05; no occlusion group 20/20 to 20/16, P < .01). The occlusion group exhibited a significant decrease in the difference in acuity between the dominant and amblyopic eyes of 1.3 lines (P < .02), whereas the no occlusion group revealed no significant effect. A comparison between groups revealed a significantly greater improvement in visual acuity in the amblyopic eye in the occlusion group compared with the no occlusion group (P = .01). In contrast, there was no significant difference between groups in terms of the change in visual acuity in the dominant eye (P = .15). Mean log contrast sensitivity in the amblyopic eye significantly improved in the occlusion group and did not significantly change in the no occlusion group. Fusion changed similarly in both groups. The improvements in visual function were maintained 4 weeks after the termination of all treatment. Adverse side effects were minimal in both groups. CONCLUSION: The combination of levodopa-carbidopa and occlusion improves visual function more than levodopa-carbidopa alone in older amblyopic children.

Levodopa-carbidopa and childhood retinal disease.

PURPOSE: Our purpose was to determine the influence of levodopa-carbidopa on visual function in children with retinal disease. METHOD: Two studies were undertaken, a single-dose study and a longitudinal dosing study. A double-masked, placebo controlled single-dose study was undertaken of levodopa-carbidopa (2.08 mg/kg of body weight levodopa with 25% carbidopa) on monocular visual acuity in 14 children with retinal disease. Subjects received two capsules approximately 2.5 hours apart, and monocular visual acuity was measured 2 hours after each capsule ingestion. The second study was a double-masked, placebo-controlled 12-week longitudinal dosing (0.62 mg/kg of body weight) crossover study in which subjects received levodopa-carbidopa for 6 weeks and placebo for 6 weeks. RESULTS: The single-dose study revealed a small but statistically significant improvement in monocular visual acuity after levodopa-carbidopa ingestion. The longitudinal study revealed a small but statistically significant improvement in binocular visual acuity after levodopa ingestion. In both studies placebo had no significant effect on visual acuity. Six subjects participated in both studies and demonstrated a significant correlation (r = 0.76, p < 0.05) between change in visual acuity in the single-dose study and the longitudinal dosing study. CONCLUSION: The results are consistent with the hypothesis that dopamine influences the receptive field characteristics of retinal cells. The results also suggest that there may be low retinal dopamine levels in some types of retinal disease, which may be amenable to treatment.

Vernier acuity in amblyopic and nonamblyopic children.

We measured vernier acuity in normal and amblyopic children using a procedure that resembles a video game and is suitable for testing most children older than 4 years old. In this procedure, subjects align bars using two keys of a computer keypad. Following binocular practice trials, monocular vernier acuity was measured in 38 control children, 5 to 15 years old, and in 18 children with histories of amblyopia. Vernier acuity was defined as the standard deviation of adjusted position across a block of six trials. Vernier acuity improved as a function of age in the control subjects, indicating developmental improvement. Amblyopic subjects with strabismus (n = 5) and with both anisometropia and strabismus (n = 8) showed markedly impaired vernier acuity in their amblyopic eyes, with vernier acuitys four to five times larger than those of age-matched controls. However, the amblyopic subjects who were anisometropic (n = 5), without any history of strabismus, were not significantly different from control subjects in either eye. Testing with bars and gratings gave similar results. To our knowledge, this is the first study showing that vernier acuity deficits seen in adult amblyopes are also seen in child amblyopes.

Levodopa/carbidopa treatment for amblyopia in older children.

The purpose of the present study is to determine how long visual function improves during levodopa/carbidopa with part-time occlusion treatment in older amblyopic children. A 7-week open clinical trial of levodopa (0.55 mg/kg, three times daily) with 25% carbidopa combined with part-time occlusion (3 hours/day), was undertaken in 15 older (mean age, 8.87 years) amblyopic children. Visual acuity, fusion, and stereo acuity were measured at baseline, at weeks 1, 3, 5, and 7 during treatment, and 6 weeks following the end of all treatment. Health status was assessed by physical examination, questionnaire, and standard laboratory tests (CHEM 20, complete blood cell count [CBC], and differential). The results revealed that visual acuity in the amblyopic eye improved for 5 weeks, from 20/170 at baseline to 20/107, then stabilized for the last 2 weeks. Visual acuity also improved in the dominant eye by 0.6 lines, from 20/19 to 20/16. At the 6-week follow up, visual acuity in the amblyopic eye remained at 20/107 (paired t = 4.78, df = 14, P < .001), a 37% improvement. Thirty-three percent of the subjects demonstrated improved fusion from baseline to the 7-week trial that was maintained at follow up (chi 2 = 3.97, P < .05). Stereo acuity did not significantly change. Physical exam (blood pressure, body temperature, respiration, heart rate) and standard laboratory tests remained normal and side effects were minimal.(ABSTRACT TRUNCATED AT 250 WORDS)

Flash visual evoked response binocular summation in normal subjects and in patients with early-onset esotropia before and after surgery.

Flash visual evoked responses were recorded and visual evoked response binocular summation was assessed in normal children between the ages of 1 and 58 months, in normal adults and in children with early-onset esotropia before and longitudinally for 1 year after surgical binocular alignment. Normal flash visual evoked response binocular summation started in the range of facilitation (> 2.0) at 1 month of age and decreased to adult levels by 3.7 months of age. The shape of the flash visual evoked response binocular summation function obtained from the patients with early-onset esotropia, appeared similar to that of normal subjects; however, the rapid decrease in flash visual evoked response binocular summation from facilitation to normal adult levels occurred after surgical binocular alignment. In normal adults, flash visual evoked response binocular summation was significantly reduced by a 40-diopter base-in prism, suggesting that binocular misalignment was not the reason for the facilitation in flash visual evoked response binocular summation in either childhood population. It is proposed that this facilitation may reflect a process that leads to binocularity and that develops rapidly with binocular alignment.

SKILL card results in amblyopic children.

Two experiments were undertaken to assess high contrast-high luminance (HCHL) and low contrast-low luminance (LCLL) visual acuity as measured with the Smith-Kettlewell Institute Low Luminance (SKILL) card, in childhood amblyopia. In experiment 1, HCHL and LCLL visual acuity was measured in 11 amblyopic children and in 12 normal children of similar age. The results revealed that HCHL visual acuity was similar in the normal eyes and in the amblyopes' dominant eyes, and was abnormal in 91% of the amblyopic eyes. LCLL visual acuity was significantly worse in normal eyes compared to the amblyopes' dominant eyes, and was abnormal in only 64% of the amblyopic eyes. In experiment 2, HCHL and LCLL visual acuity was measured in seven previously tested amblyopic children, after a 5-month interval, and in six additional amblyopic children. In the amblyopic children who were tested twice, significant test-retest reliability for HCHL and LCLL visual acuity was found and visual acuity varied by 3.6%. The results of experiment 2 corroborated the results of experiment 1 from the amblyopic children. It is concluded that visual acuity in the amblyopic eye tends to normalize under low contrast-low luminance conditions. In addition, the mechanism(s) underlying amblyopia appear also to influence the dominant eye, resulting in superior visual acuity under low contrast-low luminance conditions.

Longitudinal study of levodopa/carbidopa for childhood amblyopia.

To determine the tolerability and efficacy of levodopa/carbidopa combined with occlusion therapy for childhood amblyopia, a double-masked placebo-controlled randomized longitudinal study was performed on 10 amblyopic children between 6 and 14 years of age. Subjects received, on average, 20/5 mg levodopa/carbidopa or 20 mg of placebo three times per day combined with part-time occlusion over a 3-week period. Visual function was assessed by Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity charts and by contrast sensitivity. Tolerability was assessed by questionnaire, SMAC (standard laboratory tests; consists of a chem 20 and complete blood count [CBC]) analysis, and physical examination. Compliance with occlusion and capsule consumption were assessed by questionnaire and by capsule count, respectively. At the end of the dosing regimen, the levodopa/carbidopa group significantly improved in visual acuity by 2.7 lines and in mean contrast sensitivity by 72% in the amblyopic eye. The placebo group improved in visual acuity by 1.6 lines in the amblyopic eye. Tolerability and occlusion compliance were similar between groups; however, capsule ingestion compliance was significantly lower in the levodopa/carbidopa group. One month after the termination of treatment, the levodopa/carbidopa group maintained a significant 1.2-line improvement in visual acuity and 74% improvement in contrast sensitivity in the amblyopic eye. The placebo group did not maintain an improvement in visual acuity between the eyes. It is concluded that levodopa/carbidopa, at an average of 0.48/0.12 mg/kg, is well tolerated and, when combined with part-time occlusion, is efficacious in improving visual function in amblyopic children.

Levodopa/carbidopa for childhood amblyopia.

PURPOSE: To evaluate the efficacy and tolerance of two low doses of levodopa/carbidopa (25/6.25 mg, 50/12.5 mg) and placebo (Tums) in 20 children with amblyopia between the ages of 4 and 14 years. METHODS: A double-masked placebo-controlled randomized 8-hour study was performed during which subjects received one of two doses of levodopa/carbidopa or placebo, combined with occlusion of the dominant eye. Visual acuity was measured at baseline and at 1 and 5 hours after capsule ingestion. Tolerance was assessed by questionnaire and physical examination. RESULTS: Visual acuity significantly improved by one line, from an overall average of 20/121 to 20/96, in the amblyopic eyes of both groups that received levodopa/carbidopa. Visual acuity did not significantly change in the placebo group. Tolerance was similar among all three groups. CONCLUSION: Average dose levels of 0.95/0.24 mg/kg and 1.94/0.49 mg/kg of levodopa/carbidopa were found to be well tolerated and efficacious at temporarily improving visual acuity in amblyopic eyes of children.

Persistently altered T cell immunity in high school students with the congenital rubella syndrome and profound hearing loss.

Because there are frequent progressive and autoimmune complications in children born with the congenital rubella syndrome, we evaluated immunoregulation in eight profoundly deaf adolescents with congenital rubella syndrome who lived in a state school. Serum antiviral antibodies, expressions of peripheral lymphocyte epitopes and serum soluble interleukin 2 receptor (IL-2R) content were compared with those of 16 classmates with profound hearing loss of unknown cause and of 24 age-matched, hearing students from this area. Both deaf groups showed activated but impaired T lymphocyte function compared with normals. Rubella virus alteration of T cell function was suggested in congenital rubella syndrome students by elevated numbers of both CD4+ helper and CD25+ IL-2R cells with unusually low released soluble IL-2R content. In contrast in deaf classmates elevated CD25+ and CD16+ natural killer cell groups and soluble IL-2R content with low numbers of CD4+ helper cells and CD4+ populations were of unknown etiology. Defective immunoregulation of the congenitally deaf to pathogens inherent in their environment may lead to autoimmune and other complications.

Effect of light filters on contrast sensitivity function in normal and retinal degeneration subjects.

Contrast sensitivity functions were measured with five light filters and without a filter, in the presence of a glare source, in 12 retinal degeneration subjects and 9 normal subjects. The light filters included yellow-tinted, CPF 527, NoIR 111, 0.6 neutral density and sunglasses with a 95% UV filter. Retinal degeneration subjects showed a mild improvement in contrast sensitivity at the higher spatial frequencies and maintained mean log contrast sensitivity with light filters which reduced photopic light transmission up to 75%. Normal subjects exhibited a systematic decrease of contrast sensitivity at higher spatial frequencies with all light filters and overall mean log contrast sensitivity was significantly correlated (r = 0.86, P < 0.025) with photopic light transmission of the filters. It is concluded that, when in the presence of a glare source, the benefits of certain light filters to retinal degeneration subjects is related to the reduction of overall photopic luminance.

Fundus pigmentation and the electroretinographic luminance-response function.

Dark-adapted and light-adapted electroretinographic luminance-response functions were recorded from subjects with light or dark fundus pigmentation based on digitized fundus photographs. For dark- and light-adapted electroretinograms, subjects with dark fundi had smaller b-wave amplitudes at all luminance levels. There was no significant difference in b-wave implicit time for the dark-adapted electroretinogram, but there was a significant difference for the light-adapted ERG between the two groups. The results suggest that fundus pigmentation should be considered in the interpretation of electroretinogram results. A possible mechanism for the influence of fundus pigmentation on b-wave amplitude is based on increased resistance associated with melanin.

A prospective study of ocular abnormalities in hearing impaired and deaf students.

In a prospective study of 505 hearing impaired and deaf students conducted at Children's Hospital Eye Clinic, 48.7% were found to have significant ocular abnormalities. The prevalence of myopia, astigmatism, and pathological intraocular changes was found to be significantly increased over the general population. In addition, the prevalence of ocular abnormalities generally increased with the severity of the hearing loss. Of importance was the high prevalence of rubella-consistent abnormalities in the hearing impaired and deaf student populations. Rubella syndrome may be responsible for a major portion of high refractive errors and ocular pathological changes. It is recommended that ENT specialists and pediatricians be aware of the nearly 50% chance of ocular abnormality in hearing impaired and deaf students, and that ophthalmologic examination may be valuable for identification or confirmation of the etiology of hearing impairment.

Electro-oculogram in vitamin A deficiency associated with cystic fibrosis. Short communication.

Electro-oculograms (EOGs) were recorded in a patient with cystic fibrosis and vitamin A deficiency before and during vitamin A supplementation (25,000 IU/day). Before vitamin A supplementation the EOG Arden light/dark ratio was 1.27. After seven months of vitamin A supplementation the Arden ratio increased to 3.0. These results reveal that vitamin A deficiency can cause an abnormal EOG.

Levodopa and childhood amblyopia.

A pilot study was undertaken to address the tolerance and efficacy of levodopa/carbidopa treatment for amblyopia in older amblyopic children who failed to respond to conventional occlusion therapy. Five amblyopic children, between the ages of 7 and 12 years, and two normal adults were given between 100 mg/25 mg and 400 mg/100 mg of levodopa/carbidopa, respectively, depending on body weight. A symptoms questionnaire was completed, with temperature, respiration, heart rate, and blood pressure taken periodically to assess tolerance. Blood samples were taken, via a heparin well, to assess the pharmacokinetics of levodopa, dopamine, noradrenaline, and DOPAC. Snellen visual acuity, contrast sensitivity, stereo acuity, and pattern VERs were measured periodically to assess efficacy. The results revealed a high prevalence of side effects including emesis and nausea (four of seven subjects). Pharmacokinetics revealed that maximum serum levels of levodopa occurred 30 minutes to 1 hour after drug ingestion and decreased by 50% after 2 to 4 hours. One hour after drug ingestion, Snellen visual acuity temporarily improved from an average of 20/159 to 20/83 in the amblyopic eyes. Contrast sensitivity and pattern VERs (10-minute checks) temporarily improved in both dominant and amblyopic eyes, whereas visual function remained stable in normal eyes. The improvements in visual function started to decrease 5 hours after drug ingestion. The results are discussed in the context of developing a therapeutic trial of levodopa/carbidopa for childhood amblyopia.

Antibody response to rubella virus antigen and structural proteins in retinitis pigmentosa.

Elevated serum ELISA IgG antibodies to rubella virus (RV) were found by three independent determinations in 41 (72%) of 57 adults with the retinal degeneration retinitis pigmentosa, while antibody responses to five other common neurotropic viruses were normal. However, these patients lacked clinical signs of active RV infection or known recent RV exposure, and 56 lacked IgM anti-RV antibody. Unusual relative percentages of IgG antibody to RV structural proteins compared with those of controls were found in patients' sera by radioimmunoprecipitation assay. For retinitis pigmentosa patients, percentage of RV envelope glycoprotein E1 antibody was similar to, of RV envelope glycoprotein E2 antibody was greater than, and of antibody to RV nucleocapsid C protein was lower than control percentages. Abnormal immunity to RV was also suggested by a lack of increased proliferation of lymphocytes to RV antigen despite elevated anti-RV antibody in patients with retinitis pigmentosa. Not associated with age or particular genetic pattern, these divergences from normal immunity suggest an unusual association between RV proteins and retinitis pigmentosa.

Systemic immunostimulation after retinal laser treatment in retinitis pigmentosa.

Systemic immunostimulation followed an experimental treatment trial of scatter argon laser photocoagulation directed to the retina of one eye of 10 patients with heredo-degenerative retinitis pigmentosa (RP). Significantly increased RP lymphocyte CD25, CD26, and CD4/CD26 activation epitope expressions over prelaser values and controls were found with a normalization of soluble interleukin-2 receptor secretion after laser treatment. Serum interferon-gamma was low both pre- and postlaser. Interestingly, when a panel of viral antibodies was tested, only those to rubella virus were elevated in the early postlaser period. The character of RP immunostimulation after laser-induced inflammation could be consistent with an antigenic stimulus from laser-released retinal proteins which might be of autoimmune or latent infectious origin. Enhanced immune responses may be a common but unrecognized sequellae of retinal laser.

Fundus pigmentation and the dark-adapted electroretinogram.

Dark-adapted electroretinograms were obtained over a 3.6-log range of stimulus intensities from 17 black and 15 white normal subjects. Subjects were grouped on the basis of light or dark fundus pigmentation, determined from digitized fundus photographs. B-wave amplitudes for each group were fitted by the Naka-Rushton equation, and the measures Vmax, log K, and n were determined. The luminance-response functions revealed that subjects with light fundi had larger b-wave amplitudes at all luminance levels. There was a significant difference between groups for Vmax and n but not for log K. A comparison of b-wave implicit times showed no significant difference between subjects with dark and light fundi. Ancillary tests and multiple regression analysis suggested that the relationship between Vmax and fundus pigmentation could not be attributed to age, gender, refractive error, axial length or intraocular pressure. The results have implications for the collection of normative electroretinographic data and for the interpretation of electroretinogram results.