Hirotake Fujiwara

Concordance of strabismic phenotypes in monozygotic versus multizygotic twins and other multiple births.

PURPOSE The concordance of strabismic phenotypes was examined in monozygotic versus multizygotic twins and other multiple births to study the role of genetic background in different types of commitant strabismus. METHODS Medical charts of 45 consecutive pairs of twins (16 monozygotic and 18 dizygotic twins, and 11 with unknown zygosity), 3 sets of triplets (one monozygotic and 2 trizygotic triplets), and one set of quadruzygotic quadruplets examined at 6 institutions between 1973 and 1999 were reviewed retrospectively. The concordance was defined as both or all members having either esotropia or exotropia in common. RESULTS The concordance of strabismic phenotypes was noted in 33 of 49 pairs or sets (67.3%): 14 of 17 monozygotic twins or triplets (82.4%), 10 of 21 multizygotic twins, triplets, or quadruplets (47.6%), and 9 of 11 twins with unknown zygosity (81.8%). The concordance rate was significantly higher in monozygosity than in multizygosity (P =.043, Fisher exact probability test). The predominant concordant phenotypes in monozygosity were accommodative esotropia and intermittent exotropia. CONCLUSION A high concordance rate of strabismic phenotypes, predominantly of accommodative esotropia and intermittent exotropia in monozygosity, suggests the genetic background for these types of strabismus.

Prism adaptation response is useful for predicting surgical outcome in selected types of intermittent exotropia

PURPOSE To evaluate the prevalence of prism adaptation response in Japanese patients with intermittent exotropia (X [T]) using the prism adaptation test and to assess whether patients with selected types of X [T] benefit from surgical outcome to which prism adaptation response may contribute. METHODS In a prospective study, 128 consecutive patients with X [T] between 1990 and 1995 were enrolled. The prism adaptation test was conducted by neutralizing the angle of deviation for 2 to 3 hours. Patients who showed an increase in exodeviation by 10triangle up or more with the prism adaptation test were defined as having a prism adaptation response. For classification of the pattern of X [T], we chose a value of 15triangle up as the difference between the distance and near measurements. RESULTS The percentage of patients in whom the prism adaptation response was observed at near fixation was significantly larger than those at distance fixation [35 (27%) patients versus 10 (8%) patients, P <.05]. Of 35 patients shown to have a prism adaptation response at near fixation, 21 patients (83%) had the basic type of exotropia. Fourteen patients (17%) with the basic type were changed to convergence insufficiency type because of an increase in near deviation and were defined as pseudo basic type. Patients with pseudo basic type had a significantly better surgical outcome compared with that of true basic type, whereas in the convergence insufficiency type, no definite tendency was found between the two subtypes, true and pseudo types. CONCLUSION Patients with the pseudo basic type of X [T] in whom a prism adaptation response was demonstrated had a more favorable surgical outcome.

Chromosomes 4q28.3 and 7q31.2 as New Susceptibility Loci for Comitant Strabismus

PURPOSE This study was designed to localize chromosomal susceptibility loci for comitant strabismus among Japanese families by genome-wide linkage analyses. METHODS Fifty-five Japanese families, with at least two members with comitant strabismus (esotropia and/or exotropia), were subject to full ophthalmic examination, careful ocular history, and review of medical records. DNA was obtained and genotyping was performed with PCR amplification of 400 microsatellite markers. Parametric and nonparametric linkage (NPL) analyses scores were calculated. Linkage analysis was performed for the whole set of families (55 families), and then a second analysis was performed for two subgroups with the phenotypes, esotropia and exotropia. RESULTS A multipoint parametric heterogeneity logarithm of the odds (HLOD) score of 3.62 was obtained at marker D4S1575 under a dominant model, with a NPL score of 2.68 (P=0.001). Testing under different penetrances and disease allele frequencies revealed two other susceptibility loci at 7q31.2 under a recessive model (HLOD scores=3.93 and 4.40 at 125.2 cM and 107.28 cM, respectively). Analysis of the subgroups revealed new susceptibility loci for esotropia; one locus at 8q24.21 is worthy of further investigation. CONCLUSIONS This study suggests multiple susceptibility loci for comitant strabismus. The loci at chromosomes 4q28.3 and 7q31.2 show a significant evidence of linkage.

ARIX gene polymorphisms in patients with congenital superior oblique muscle palsy

Aim: To identify ARIX gene polymorphisms in patients with congenital superior oblique muscle palsy and to find the relation between the ARIX gene and congenital superior oblique muscle palsy. Methods: The three exons of the ARIX gene were sequenced by genomic DNA amplification with polymerase chain reaction (PCR) and direct sequencing in 15 patients with superior oblique muscle palsy (13 with congenital and two with acquired palsy) and 54 normal individuals. PCR products cloned into plasmids were also sequenced. A family with father and a daughter each having congenital superior oblique muscle palsy was also involved in this study. Results: Four patients with congenital superior oblique muscle palsy carried heterozygous nucleotide changes in the ARIX gene. One patient with the absence of the superior oblique muscle had T7C in the 5′-UTR of the exon 1 and C-44A in the promoter region, both of which were located on the same strand. Another unrelated patient with congenital superior oblique muscle palsy had C76G in the 5′-UTR of the exon 1 and C-9A in the promoter region on the same strand. G153A in the 5′-UTR of exon 1 was found in common in two affected members of a family with congenital superior oblique muscle palsy. This G153A in the 5′-UTR of exon 1 was also present in four unrelated normal individuals. No other heterozygous nucleotide changes were found in normal individuals. Conclusions: The nucleotide change (G153A) in the 5′-UTR of exon 1 co-segregated with congenital superior oblique muscle palsy in one family. Four other nucleotide changes in the exon 1 or the promoter region were found only in patients with congenital superior oblique muscle palsy. These nucleotide polymorphisms may be one of the risk factors for the development of congenital superior oblique muscle palsy.

Predictive factors for long-term outcome of stereoacuity in Japanese patients with pure accommodative esotropia.

Purpose: To find clinical factors related to the long-term outcome of stereoacuity in Japanese patients with pure accommodative esotropia, including both the refractive type and the nonrefractive type. Methods: The medical charts of 19 Japanese patients (8 boys and 11 girls) with pure accommodative esotropia who were followed for 10 years or more at Okayama University Hospital were reviewed retrospectively. Refractive accommodative esotropia was diagnosed in 8 patients while nonrefractive accommodative esotropia was diagnosed in 11 patients. The patients were divided into two groups, based on a stereoacuity of 120 seconds of arc or better versus 240 seconds of arc or worse as measured by the TNO test at the final visit, and the clinical factors were compared between the two groups. Results: Clinical factors related to a stereoacuity of 240 seconds of arc or worse at the final visit were higher accommodative convergence to accommodation (AC/A) ratios at 6 years of age (p = 0.05), larger residual esodeviations at distance under full correction with glasses at 8 years of age (p = 0.03), and larger residual esodeviations at near at 6 years of age (p = 0.01, Mann-Whitney U-test). Overall, patients with nonrefractive accommodative esotropia tended to show poor levels of stereoacuity at the final visit compared to those with refractive accommodative esotropia (p = 0.059, Fisher exact probability test). Conclusion: This is the first study of the long-term visual outcome in Japanese patients with pure accommodative esotropia including both refractive and nonrefractive types. To obtain better levels of stereoacuity, the residual esodeviations at near and at distance should be kept as small as possible under full correction with glasses, including bifocals, especially at the ages of 6 and 8 years.

Large Bielschowsky head-tilt phenomenon and inconspicuous vertical deviation in the diagnostic positions in congenital superior oblique palsy

PURPOSE To report a case of congenital superior oblique palsy with an unusually large Bielschowsky head-tilt phenomenon (BHP) and disproportional inconspicuous vertical deviation. METHODS Case report. RESULTS An 18-year-old woman presented with slight compensatory head tilting and a Bielschowsky head-tilt phenomenon of 50 Delta on left tilting. Magnetic resonance imaging revealed atrophy of the left superior oblique muscle. A Hess screen test showed a slight underaction of the left superior oblique muscle, but neither an obvious overaction of the ipsilateral inferior oblique muscle nor inhibitory palsy of the contralateral superior rectus muscle was found. With a 3-mm recession of the ipsilateral superior rectus muscle, Bielschowsky head-tilt phenomenon decreased to 25 Delta. CONCLUSION A large Bielschowsky head-tilt phenomenon was possibly caused by an increased gain of the otolith-ocular reflex affecting the vertical rectus muscle.

Correction of Cyclovertical Strabismus Induced by Limited Macular Translocation in a Case of Age-Related Macular Degeneration

PURPOSE To report a case of strabismus surgery performed to treat cyclovertical strabismus induced by limited macular translocation. METHODS Case report. RESULTS A 62-year-old man suffering with age-related macular degeneration and subfoveal choroidal neovascularization, RE, underwent limited macular translocation surgery. The fovea was rotated downward, and his visual acuity improved from 20/100 to 20/25 postoperatively. Cyclovertical diplopia persisted for 6 months after the operation. A Hess screen test revealed a pattern that simulated an underaction of the superior oblique muscle and inferior rectus muscle with an overaction of the ipsilateral inferior oblique muscle. To treat the diplopia, advancement of the superior oblique muscle tendon and resection of the ipsilateral inferior rectus muscle were performed. Binocular single vision with 140 seconds of arc for stereopsis was obtained. CONCLUSION Cyclovertical strabismus after limited macular translocation is corrective with conventional surgery on the treated eye.