Optical penalization can improve vision after occlusion treatment.

BACKGROUND: Optical penalization (OP) has previously been shown to successfully maintain vision in amblyopic eyes of older children when patching compliance is poor and when vision decreases once patching is discontinued. This study shows that the final vision in optically penalized eyes is often better than the vision obtained after patching alone. SUBJECTS AND METHODS: During the 5-year period from January 1992 to February 1997, 28 children aged between 3.7 and 8.2 years (average age, 6.5+/-1.1 years) were optically penalized for an average of 1.5+/-0.75 years. The maximum length of penalization was 3.3 years, whereas the minimum time was 6 months. There were 21 children with strabismic amblyopia and 7 children with anisometropic amblyopia. All 28 children had worn a patch to achieve their best visual levels and then had shown a loss of best vision when occlusion was stopped. Patching was usually resumed and continued until the previous best vision was obtained; at this point OP was started to "maintain" vision. Eighteen of the 28 children have discontinued penalization and have been followed up an average of 1(1/2) years. RESULTS: Twenty-six (93%) of the 28 patients showed an increase in best vision from that found at the conclusion of patching, and 2 patients maintained their vision at the initial level. The average visual acuity at the start of penalization was 20/50 (0.42+/-0.11 logarithm of the minimum angle of resolution [log MAR]). Final average visual acuity was 20/27 (0.15+/-0.12 log MAR). The average increase in vision was nearly 3 lines or 0.27+/-0.12 log MAR. CONCLUSION: OP alone (without the use of pharmacologic agents such as atropine) not only maintains vision after patching therapy, but also appears to improve the final visual outcome.

Homonucleotide expansion and contraction mutations of PAX2 and inclusion of Chiari 1 malformation as part of renal-coloboma syndrome.

Renal-Coloboma syndrome, an autosomal dominant disorder characterized by colobomatous eye defects, vesicoureteral reflux, and abnormal kidneys, results from mutations in PAX2. The purpose of this study was to identify mutations in PAX2 and understand the associated patient phenotypes. We report a severely affected girl and a mildly affected mother and daughter, all of whom have PAX2 homoguanine tract (7 G) missense mutations. The mother and daughter have optic nerve colobomas and the daughter has vesicoureteral reflux. The severely affected girl developed renal failure and has bilateral colobomatous eye defects. Additionally, this girl developed hydrocephalus associated with platybasia and a Chiari 1 malformation. We examined genomic DNA from these individuals by SSCP and sequencing. The mother and daughter had a novel mutation: a contraction in a string of 7 G's to 6 G's in one allele of PAX2, leading to a premature stop codon two amino acids downstream. The severely affected girl had an expansion to 8 G's, leading to a premature stop codon 27 amino acids downstream. The 8 G expansion has been found in other patients without brain anomalies and has occurred spontaneously in a mouse model, PAX2(1Neu). We expand the known phenotype associated with mutations in PAX2 to include brain malformations. The homoguanine tract in PAX2 is a hot spot for spontaneous expansion or contraction mutations and demonstrates the importance of homonucleotide tract mutations in human malformation syndromes.

A sweep VEP test for color vision deficits in infants and young children.

PURPOSE: Color vision testing in young children typically is precluded by the motor and cognitive skills required by standard tests; yet this information can be useful for diagnosis and counseling in many conditions. The purpose of this study is to evaluate a visual evoked potential (VEP) method for assessing red-green color vision anomalies in pediatric patients. METHOD: The relative chromatic luminance (C = R/R + G) of a rapidly reversing red-green checkerboard was varied across a wide range within a short viewing period (10 sec). Swept-parameter VEP methods were used to measure the cortical response to the range of C presented. RESULTS: Individuals with normal color vision exhibit a VEP response that exceeds noise levels across all values of C, often with an amplitude minima near the photopic equiluminant point (C = 0.5). Results from children with established protan and deutan color vision anomalies show loss of VEP amplitude and phase at values of C consistent with the respective color defect. A patient with achromatopsia showed a generalized depression of VEP response across all values of C tested. CONCLUSION: Color sweep VEP techniques appear promising for the clinical assessment of color status in pediatric patients.

Binocular cortical interactions in the monofixation syndrome.

This study examines the relationship between clinically assessed binocular sensory status and binocular visual evoked potentials (BVEPs) in 11 patients with monofixation syndrome (MFS) and in 12 patients with absent binocular fusion (ABF). BVEPs were elicited using a two-sinusoid "beat" technique. The luminances of red/green anaglyphic circular fields were modulated independently at temporal rates of 6 and 8 Hz. This stimulus elicits a BVEP at 14 Hz in children with normal stereoscopic vision. In this study, we found that this BVEP also is present in patients with MFS, whereas it is near background noise levels in patients with ABF. These results demonstrate the presence of functional binocular cortical mechanisms in patients with MFS. The findings are consistent with the hypothesis that elicitation of this class of BVEPs requires gross sensory fusion, but not fine stereoscopic vision.

VECP evidence for binocular function in infantile esotropia.

Since commonly used clinical methods of measuring binocular function require subjective responses, this testing has been limited to more cooperative children, usually older than 2 years of age. Recently, we have begun using a clinically practical, visually evoked cortical potential (VECP) method to detect the presence of binocular neurons in infants and young children. We studied 14 children, ages 4 to 44 months, with infantile esotropia. Nine had surgical correction for esotropia by the age of 2 years. Twenty-five normal infants ages 6 weeks to 22 months served as controls. Most normal infants showed the development of the "beat" by 2 months of age. The "sum" VECP was not consistently present until age 6 months. Four of the five esotropic infants less than 1 year of age, demonstrated neither a "sum" nor "beat" response. All nine patients with corrective surgery performed before 2 years of age developed a significant sum response and three developed a beat. Five patients had not had surgery until after 2 years of age. Two developed a sum and one a beat, but none had both beat and sum responses. The results suggest that there is a loss of nonlinear binocular response in esotropic children not corrected before the age of 2 years and that these responses can be restored after early treatment even if not present at the time of surgery.

Ocular findings in CHARGE syndrome. Six case reports and a review.

CHARGE syndrome is a group of nonrandomly occurring congenital anomalies which may present to the ophthalmologist, because coloboma is one of the major findings. In a series of 54 patients with ocular colobomata, 6 (11%) were found to meet the criteria for CHARGE syndrome. The mnemonic CHARGE stands for the major features of this syndrome: Coloboma, Heart defects, Atresia of the choanae, Retarded growth and development, Genital hypoplasia, and Ear anomalies and/or hearing loss. No specific etiology is known, but autosomal dominant, autosomal recessive, and X-linked recessive forms have been suggested by familial reports. The authors describe six patients with CHARGE syndrome, including the second reported case occurring in monozygotic twins. Other syndromes, chromosomal defects, and effects of teratogens may have similar clinical presentations. Though our prevalence may be skewed by our referral setting, the frequency of occurrence of this syndrome is certainly high enough that ophthalmologists should be familiar with it. Evaluation for associated defects should be carried out and referral for genetic evaluation undertaken when appropriate.

Paradoxic pupillary phenomena. A review of patients with pupillary constriction to darkness.

The presence of pupillary constriction to darkness is said to be a useful indicator of retinal disease. However, it is also associated with optic nerve disease. The phenomenon has been reported in patients with congenital stationary nightblindness, congenital achromatopsia, bilateral optic neuritis, and dominant optic atrophy. We have observed this response in additional disorders, including anomalies of the optic nerve development, congenital nystagmus, and a variety of diseases affecting the retina. Notably, four of our patients with strabismus and amblyopia, but without apparent retinal or optic nerve disease, have also demonstrated this paradoxic pupil response. While the mechanism for pupillary constriction to darkness remains unclear, the finding of this response in patients without retinal or optic nerve abnormalities questions its value as a localizing sign.

Growth factor receptors and oncogene expression in prostate cells.

Specimens of benign prostatic hypertrophy (BPH) and prostate carcinoma and prostate cells in culture were assessed for their capacity to bind androgens, radioiodinated EGF, and IGF-I, and to express certain cellular protooncogenes. Prostate cell lines contained receptors for both EGF and IGF-I. Similarly, clinical samples of human diseased prostate contained receptors for both of these factors. Prostate carcinoma contained higher concentrations of EGF receptors based on DNA than did BPH, although it is accepted that BPH may not be the appropriate comparison for carcinoma. Increased EGF receptors were associated circumstantially with a decline in androgen receptors with deteriorating differentiation status and with an increase in expression of c-myc. Androgen receptor concentration correlated with increased expression of c-fos. Deteriorating differentiation status was associated with the appearance or increase in secondary sites with lower affinity for IGF-I. Whereas c-myc expression was increased in all grades of carcinoma compared to BPH, expression of c-H-ras accompanied loss of differentiation. Although those alterations are hindered by tissue heterogeneity and correlations are essentially circumstantial, they may provide clues to the progression of prostate cancer that can be validated in prostate cell lines with similar growth response capabilities.

Low-contrast visual acuity cards in pediatric ophthalmology.

The usual high-contrast visual acuity chart is well known as the best indicator of central visual function. It has the limitation of only testing the high frequency, high-contrast sensitive cells in the visual system. Some conditions demonstrate a normal response on the standard visual acuity test, but abnormal results when testing visual fields or contrast-sensitivity function (CSF). A variety of diseases fall into this category (multiple sclerosis, diabetes mellitis, glaucoma, CNS tumors in the visual system, etc). The testing of CSF permits us not only to vary the size of the target (spatial frequency), but also to determine the contrast of the target first visible to the patient. Due to the time necessary to conduct the test and the important challenge of obtaining consistent subjective responses, contrast-sensitivity testing in children has been difficult. Recently, Regan has developed low-contrast visual acuity cards similar in format to those used in the Sheridan Gardiner test. Although they do not require literacy, correct responses can be immediately verified and the test can be carried out within a short period of time. These cards allow testing well within the child's limited attention span. In the future it may be possible to use this method of testing to detect CSF defects in amblyopia similar to those previously reported by Hess and others and to see how these defects are affected by standard treatment.

Persistent accommodative spasm nine years after head trauma.

Spasm of the near reflex is most often seen on a functional basis in young adults with underlying emotional problems. In particular, when convergence spasm is associated with miosis on attempted lateral gaze, a functional basis for the disorder should be suspected. Patients who experience spasm of the near reflex following trauma commonly follow a benign course with spontaneous resolution of their ocular complaints within 1-2 years. Accommodative spasm, manifested by pseudomyopia, or spasm of convergence, alone, or in combination with miosis, may be found as isolated signs of spasm of the near reflex. We report a patient who continues to demonstrate accommodative spasm 9 years after a motor vehicle accident.

The pattern evoked electroretinogram: its variability in normals and its relationship to amblyopia.

Electroretinograms evoked by pattern stimuli (contrast reversing gratings) were measured under steady state conditions in the normal and amblyopic eyes of 14 amblyopic individuals having Snellen acuities in the range 20/100 to 20/600. These ERGs were measured as a function of spatial frequency, and compared with the psychophysical threshold losses to the same stimuli. In all cases the authors compared the normal and fellow amblyopic eye's response while taking into account the variability of right-left eye comparisons of normal individuals for these psychophysical and electrophysiological tests. When factors such as optical focus, fixation alignment, and fixation stability have been individually optimized, no pattern ERG deficit was observed in a spatial frequency range where there were obvious psychophysical deficits to the same stimuli. Our results do not substantiate previous claims of a pattern ERG anomaly in many severely amblyopic eyes.