Valproic Acid Inhibits Human Retinal Pigment Epithelial (hRPE) Cell Proliferation Via a P38 MAPK Signaling Mechanism.

Valproic acid (VPA) has been reported to inhibit cancer cell growth and has therapeutic use in retinal diseases. However, the mechanism of this action remains unclear. In order to explore this mechanism, primary human retinal pigment epithelial (hRPE) cell cultures were established. Cell viability was assessed by the trypan blue exclusion method (T), and the cell proliferation was measured by 3H-thymidine incorporation (3H-thy). P38 synthesis was quantitated by using 14C-methionine-labeled P38 (14C-P38) by using P38-specific antibody. SB203580 (SB), a selective inhibitor of p38 MAPK, was also used to test the specificity of P38 stimulation. Antinuclear staining (NS) studies were performed by DAPI. Statistical significance was established by student's t-test. We observed that VPA (1 mM) inhibited 10% fetal bovine serum (FBS)-stimulated cell proliferation (1.75 ± 0.37 vs. 3.25 ± 0.68 cells per 1 µl ± SEM, p < 0.05, n = 4). VPA also stimulated 14C-P38 synthesis in a dose-dependent manner. SB (30 µM) inhibited VPA (4 mM)-stimulated 14C-P38 synthesis (197.74 ± 41.17 vs. 425.89 ± 59.17, CPM ± SEM, p < 0.05, n = 4) and increased hRPE cell proliferation (1.79 ± 0.45 vs. 4.93 ± 1.12 cells per 1 µl ± SEM, p < 0.05, n = 4); NS demonstrated VPA-induced cell damage. We conclude that VPA inhibits hRPE cell growth via P38 MAP mechanism and may be of therapeutic value in treating or preventing proliferative eye diseases.

Valproic Acid Induced Human Retinal Pigment Epithelial Cell Death as Well as its Survival after Hydrogen Peroxide Damage is Mediated by P38 Kinase.

Age-related macular degeneration (AMD) is a leading cause of legal blindness in developed countries. Several new drugs are now available to reduce the sight threatening complications of this disease, however, all are useful in only a small fraction of patients and none of them prevents disease development. An understanding of the pathogenesis of the retinal and macular degeneration is the first step in developing preventive and fully effective treatment options for this condition. Lifelong oxidative stress seems to be an etiologic factor. In this study, we used cultured human retinal pigment epithelial cells to study the mechanism of cell death and survival in cells exposed to oxidative stress. Our studies demonstrate that valproic acid (VPA), an epigenetic factor, reduces apoptosis in hRPE cells that were subjected to hydrogen peroxide-induced oxidative injury by alteration in P38 kinase activity. Since VPA has been shown to have therapeutic use in other neuronal diseases, better understanding of the mechanism of this VPA anti-apoptotic activity may enhance its development as a therapeutic agent.

Doses of medial rectus muscle recessions for divergence insufficiency-type esotropia.

We evaluated whether doses of bilateral medial rectus recessions greater than Parks's tables yielded superior outcomes for adult-onset divergence insufficiency. Forty-two patients underwent bilateral medial rectus recessions. Dose was analyzed as the average total per muscle (surgery + suture adjustment if performed) and compared with the standard dose tables (based on preoperative distance esodeviation), as difference between dose performed and dose indicated by Parks's tables. Each participant was classified as having received either Parks's dose (within 0.5 mm) or a dose greater than Parks's dose. Success was defined as "rarely" or "never" diplopia in distance straight-ahead gaze and reading. For patients classified as success, the mean difference between actual surgical dose performed and Parks's dose was calculated. Success was 91% (29/32) in those receiving greater than Parks's dose versus 67% (6/9) with Parks's dose (difference = 24%; 95% CI, -5% to 60%). The mean surgical dose was 1.0 mm greater than Parks's tables for the 35 successes (at 10 weeks) versus 0.7 mm greater for the 6 failures (difference = 0.4 mm; 95% CI, -0.2 to 0.9). For medial rectus recessions in adult-onset divergence insufficiency-type esotropia, a surgical dose 1 mm greater than Parks's tables, for each muscle, is a reasonable strategy.

Heterozygous mutations of the kinesin KIF21A in congenital fibrosis of the extraocular muscles type 1 (CFEOM1).

Congenital fibrosis of the extraocular muscles type 1 (CFEOM1; OMIM #135700) is an autosomal dominant strabismus disorder associated with defects of the oculomotor nerve. We show that individuals with CFEOM1 harbor heterozygous missense mutations in a kinesin motor protein encoded by KIF21A. We identified six different mutations in 44 of 45 probands. The primary mutational hotspots are in the stalk domain, highlighting an important new role for KIF21A and its stalk in the formation of the oculomotor axis.

Prevalence of cerebrotendinous xanthomatosis among patients diagnosed with early-onset idiopathic bilateral cataracts: final analysis.

Cerebrotendinous xanthomatosis (CTX) is a rare, autosomal recessive bile acid synthesis disorder caused by pathologic variants in CYP27A1, a gene involved in bile acid synthesis. Impaired function in this gene leads to accumulation of plasma cholestanol (PC) in various tissues, often in early childhood, resulting in such clinical signs as infantile diarrhea, early-onset bilateral cataracts, and neurological deterioration. The current study aimed to identify cases of CTX in a population of patients with a greater CTX prevalence than the general population, to facilitate early diagnosis. Patients diagnosed with early-onset, apparently idiopathic, bilateral cataracts between the ages of 2 and 21 years were enrolled. Genetic testing of patients with elevated PC and urinary bile alcohol (UBA) levels was used to confirm CTX diagnosis and determine CTX prevalence. Of 426 patients who completed the study, 26 met genetic testing criteria (PC ≥ 0.4 mg/dL and positive UBA test), and 4 were confirmed to have CTX. Prevalence was found to be 0.9% in enrolled patients, and 15.4% in patients who met the criteria for genetic testing.

Comparison of Unilateral and Bilateral Surgical Approaches for the Treatment of Age-Related Divergence Insufficiency Esotropia.

PURPOSE: Age-related divergence insufficiency-esotropia (ARDIE) is characterized by greater esodeviation at distance than near. This study aims to compare the outcomes of unilateral and bilateral surgical approaches. PATIENTS AND METHODS: Sixty-two cases treated at the Kellogg Eye Center, the University of Michigan, from 1995 to 2018 were retrospectively reviewed. One surgeon used unilateral procedures including unilateral medial rectus recession (n = 24, group 1) or unilateral recession-resection (n = 18, group 2) with an adjustable suture. Another surgeon used bilateral medial rectus recession with fixed sutures (n = 20, group 3). RESULTS: For patients with distance esodeviation <15∆, postoperative distance deviations in both group 1 and group 3 were not statistically different (p = .352). For patients with esodeviations 15-20∆, postoperative distance deviations in all 3 groups were also not statistically different (p = .142). Similarly, patients with deviations >20∆ did not show significantly different postoperative distance alignment (p = .082) between group 2 and 3. Overall, group 2 had the highest overall success rate (90%) (mean at distance = 1.17∆ exodeviation, at near = 2.33∆ exodeviation). CONCLUSION: Both unilateral medial rectus recession ± lateral rectus resection and bilateral medial rectus recession surgical approaches produced similar favorable outcomes in ARDIE.

Contralateral Surgery for the Treatment of Third Nerve Palsy with Aberrant Regeneration.

PURPOSE: To report the results of contralateral recession-resection of the horizontal muscles in oculomotor nerve palsy with aberrant regeneration to correct both the strabismus and the ptosis in one procedure. DESIGN: Retrospective case series. METHODS: This is an institutional study on patients with oculomotor nerve palsy with aberrant innervation who had contralateral eye muscle surgery in 2 different centers. Patients were included if they have both exotropia and aberrant regeneration with a ptosis that improved on adduction. All patients had contralateral lateral rectus recession and medial rectus resection. Ductions, versions, angle of misalignment, and degree of ptosis were evaluated before surgery and at last follow-up. RESULTS: Eleven patients were identified. The mean age at surgery was 15.0 ± 9.2 years. Five patients were male (45%). Trauma was the cause in 8 (72%) cases. The mean angle of exotropia was 42 ± 14 prism diopters. The mean degree of ptosis was 3.9 ± 1.6 mm. The mean lateral rectus recession was 8.2 ± 1.1 mm, and the mean medial rectus muscle resection was 6.7 ± 0.9 mm. The mean follow-up was 6.4 ± 2.5 months. After surgery, none of the patients had residual exotropia >10 prism diopters. The mean degree of ptosis after surgery was 0.9 ± 0.8 mm. None of the patients required further surgery for ptosis or strabismus. CONCLUSION: Contralateral eye muscle in third nerve palsy with aberrant innervation offers the advantage of simultaneous correction of both strabismus and ptosis through a single procedure.

A prospective study of treatments for adult-onset divergence insufficiency-type esotropia.

PURPOSE: To describe 10-week and 12-month outcomes following treatment for divergence insufficiency-type esotropia in adults. METHODS: In this prospective observational study, 110 adults with divergence insufficiency-type esotropia, with a distance esodeviation measuring 2Δ to 30Δ and at least 25% larger at distance than near, and binocular diplopia present at least "sometimes" at distance, were enrolled at 28 sites when initiating new treatment. Surgery, prism, or divergence exercises/therapy were chosen at the investigator's discretion. Diplopia was assessed at enrollment and at 10-week and 12-month outcome examinations using a standardized diplopia questionnaire (DQ). Success was defined as DQ responses of "rarely" or "never" when looking straight ahead in the distance, with no alternative treatment initiated. RESULTS: Of the 110 participants, 32 (29%) were prescribed base-out prism; none had received prior treatment for esotropia. Success criteria were met by 22 of 30 at 10 weeks (73%; 95% CI, 54%-88%) and by 16 of 26 at 12 months (62%; 95% CI, 41%-80%). For the 76 (68%) who underwent strabismus surgery (82% of whom had been previously treated with prism), success criteria were met by 69 of 74 at 10 weeks (93%; 95% CI, 85%-98%) and by 57 of 72 at 12 months (79%; 95% CI, 68%-88%). CONCLUSIONS: In this study cohort, both base-out prism as initial therapy and strabismus surgery (usually following prism) were successful in treating diplopia for most adults with divergence insufficiency-type esotropia when assessed during the first year of follow-up.

Impaired intracellular signaling may allow up-regulation of CTGF-synthesis and secondary peri-retinal fibrosis in human retinal pigment epithelial cells from patients with age-related macular degeneration.

Age-related macular degeneration (AMD) is a major sight-threatening ocular disorder in the United States of America and the world, yet its etiology is not clearly understood, preventing the development of effective prevention or therapy. Connective tissue growth factor (CTGF) has been implicated in the pathological synthesis of peri-retinal fibrous tissue in patients with AMD. Very little is known about the mechanism of this interaction. In this study, the authors demonstrate that insulin like growth factor-1 (IGF-1) and glucose-stimulated CTGF production are not blocked by the MAP kinase pathway inhibitor, PD98059 in hRPE cells obtained from eyes of a patient with AMD in contrast to hRPE cells obtained from normal human eyes. This suggests that there may be abnormal CTGF synthesis regulation in AMD, which may play a role in fibrous peri-retinal membrane formation in patients with AMD-related proliferative vitreoretinopathy.

Novel TMEM98, MFRP, PRSS56 variants in a large United States high hyperopia and nanophthalmos cohort.

Nanophthalmos is a rare condition defined by a small, structurally normal eye with resultant high hyperopia. While six genes have been implicated in this hereditary condition (MFRP, PRSS56, MYRF, TMEM98, CRB1,VMD2/BEST1), the relative contribution of these to nanophthalmos or to less severe high hyperopia (≥ + 5.50 spherical equivalent) has not been fully elucidated. We collected probands and families (n = 56) with high hyperopia or nanophthalmos (≤ 21.0 mm axial length). Of 53 families that passed quality control, plausible genetic diagnoses were identified in 10/53 (18.8%) by high-throughput panel or pooled exome sequencing. These include 1 TMEM98 family (1.9%), 5 MFRP families (9.4%), and 4 PRSS56 families (7.5%), with 4 additional families having single allelic hits in MFRP or PRSS56 (7.5%). A novel deleterious TMEM98 variant (NM_015544.3, c.602G>C, p.(Arg201Pro)) segregated with disease in 4 affected members of a family. Multiple novel missense and frameshift variants in MFRP and PRSS56 were identified. PRSS56 families were more likely to have choroidal folds than other solved families, while MFRP families were more likely to have retinal degeneration. Together, this study defines the prevalence of nanophthalmos gene variants in high hyperopia and nanophthalmos and indicates that a large fraction of cases remain outside of single gene coding sequences.

Prevalence of Cerebrotendinous Xanthomatosis Among Patients Diagnosed With Acquired Juvenile-Onset Idiopathic Bilateral Cataracts.

IMPORTANCE: Cerebrotendinous xanthomatosis (CTX) is a rare autosomal recessive bile acid synthesis disorder caused by mutations in CYP27A1, the gene encoding sterol 27-hydroxylase, which results in elevated levels of plasma cholestanol and urinary bile alcohols. Clinical symptoms and signs may include early-onset chronic diarrhea, juvenile-onset bilateral cataracts, cholestatic jaundice, tendon xanthomas, and progressive neurological deterioration. Although initiation of treatment at a young age can prevent disease complications, diagnosis often occurs after the onset of permanent neurologic damage. Strategies are needed to facilitate early diagnosis. OBJECTIVE: To evaluate the prevalence of CTX in a patient population diagnosed with early-onset idiopathic bilateral cataracts. DESIGN, SETTING, AND PARTICIPANTS: This interim analysis of the Cerebrotendinous Xanthomatosis Prevalence Study was conducted in 26 active US sites from November 2015 to June 2017. The study included patients diagnosed as having idiopathic bilateral cataracts from ages 2 to 21 years. Potentially eligible study participants were identified through retrospective medical record review or on receiving care for cataracts at an active site. Data were analyzed from July 2017 to October 2018. MAIN OUTCOMES AND MEASURES: Measurement of plasma cholestanol levels and optional urine bile alcohol screening were performed. A plasma cholestanol concentration of 0.4 mg/dL or greater or a positive urine bile alcohol result prompted CYP27A1 genetic testing to confirm the diagnosis of CTX. RESULTS: Of 170 tested patients, 88 (51.8%) were male, and the median (range) age was 10 (2-49) years. A total of 3 patients (1.8%) had biochemical and genetic confirmation of newly diagnosed CTX (plasma cholestanol level greater than 1.0 mg/dL, positive urine bile alcohol result, and disease-causative mutations in CYP27A1). The mean (range) age at cataract diagnosis for patients with CTX was 12 (8-16) years. Reported symptoms included abnormal gait or balance (n = 3), learning disability (n = 2), cognitive decline (n = 2), seizures (n = 2), frequent bone fractures (n = 2), and chronic diarrhea (n = 1). CONCLUSIONS AND RELEVANCE: To date, 1.8% of patients in this study were diagnosed as having CTX, which is approximately 500-fold the currently estimated prevalence of CTX in the general population (3 to 5 per 100 000). These data suggest that juvenile-onset idiopathic bilateral cataracts may be useful as a screening marker for CTX and that ophthalmologists can play an important role in facilitating early identification of this condition.

Ocular Manifestations of Cutis Marmorata Telangiectatica Congenita.

PURPOSE: To describe the range of ocular manifestations in cutis marmorata telangectatica congenita (CMTC). DESIGN: Multicenter, retrospective, nonconsecutive case series. PARTICIPANTS: Patients with a diagnosis of CMTC referred for ophthalmologic evaluation between January 1, 2015, and December 31, 2018. METHODS: Evaluation of ocular findings at presentation, systemic manifestations suggestive of a diagnosis of CMTC, genetic testing, and visual outcomes after treatment. MAIN OUTCOME MEASURES: Visual acuity, findings on ophthalmoscopy, and results of fluorescein angiography. RESULTS: Nine patients with CMTC diagnosed clinically based on stereotypical cutaneous vascular malformations were included. The median age at presentation was 8 weeks (range, 2 weeks-4 years). Six patients were female and 3 were male. Avascular retina was identified on dilated fundus examination, fluorescein angiography, or both in 11 eyes of 6 patients. Retinal neovascularization was present bilaterally in 2 patients at presentation. One patient demonstrated retinal venous tortuosity, and another patient showed mild straightening of nasal retinal vessels in both eyes. Two patients (2 eyes) demonstrated retinal detachment (RD). Both were managed surgically. One infant demonstrated RD, whereas the other child showed extensive neovascularization and later progressed to combined tractional-rhegmatogenous detachment. A unique constellation of lacy peripheral capillary anomalies with prominent terminal vascular bulbs was noted in 3 patients. Granular pigment abnormalities were noted in the macula in 5 patients. Two patients demonstrated glaucoma, 1 requiring surgical intervention. Two patients demonstrated features of Adams-Oliver syndrome, with genetic testing identifying a Notch1 mutation in 1 patient. CONCLUSIONS: Retinal vascular abnormalities in CMTC may occur more frequently than recognized previously. Given the variability of ocular involvement and the potential for rapidly progressive retinal vascular abnormalities and development of RD, complete ophthalmologic evaluation including measurement of intraocular pressure, gonioscopy, dilated fundus examination, and fluorescein angiography is recommended in infants with suspected CMTC shortly after birth. The distinct pattern of lacy capillary anomalies with prominent terminal bulbs seen in CMTC has not been described in other syndromes of vascular dysgenesis. Therefore, ophthalmic examination may be a valuable method to distinguish CMTC from other disorders demonstrating similar dermatologic and systemic manifestations.

Childhood visual impairment: normal and abnormal visual function in the context of developmental disability.

Abnormal or failed development of vision in children may give rise to varying degrees of visual impairment and disability. Disease and organ-specific mechanisms by which visual impairments arise are presented. The presentation of these mechanisms, along with an explanation of established pathologic processes and correlative up-to-date clinical and social research in the field of pediatrics, ophthalmology, and rehabilitation medicine are discussed. The goal of this article is to enhance the practitioner's recognition and care for children with developmental disability associated with visual impairment.

The effect of oral statin therapy on strabismus in patients with thyroid eye disease.

BACKGROUND: Statins, known to possess anti-inflammatory characteristics, have recently been identified as potentially reducing the risk of developing thyroid eye disease (TED) in Graves disease patients. The current study investigates the effect of oral statin therapy on strabismus related to TED. METHODS: This is a retrospective review of patients with a diagnosis of both TED and restrictive strabismus. Oral statin users and nonusers were analyzed for smoking status, previous radioactive iodine, thyroidectomy, number of decompressions, motility restriction, amount of strabismus, number of surgeries, surgical dose, and number of muscles involved on radiography. RESULTS: Thirty patients (average age, 63.9 years; 50% male; 59% current/former smokers) were included: 12 statin users and 18 nonusers. Statin users averaged fewer decompressions (1.3 in users vs 2.4 in nonusers [P = 0.04]). Statin users on average had 15 mm of total strabismus surgery compared with 21.4 mm in the nonuser group (P = 0.09) and had fewer muscles involved radiographically (4.3 vs 5.1 [P = 0.08]) CONCLUSIONS: Compared to nonusers, statin users tended to have fewer decompressions, less restriction, fewer surgeries, and fewer muscles involved despite having more current smokers (36% vs 5%), more males, more RAI, and fewer thyroidectomies, all of which are associated with worse TED. In our cohort of patients with TED and strabismus, statin therapy significantly reduced the number of orbital decompressions. Oral statin therapy also trended toward reducing the number and amount of strabismus surgeries as well as radiographic indication of muscle involvement, although these did not meet statistical significance.

Discrepancies between intraocular lens implant power prediction formulas in pediatric patients.

PURPOSE: The SRK II, SRK/T, Holladay I, and Hoffer Q intraocular lens power prediction formulas have been claimed to be interchangeable in their predicted postoperative refractive outcome among pediatric patients. In this study, we evaluated this clinical perception. DESIGN: Mathematical analysis. METHODS: Analytical prediction of implant power using keratometry values up to 55 diopters and axial length values as short as 16 mm was performed for 2 different refractive goals using the optimized intraocular lens constants for the SRK II, SRK/T, Holladay I, Hoffer Q, and Haigis formulas. Comparison graphs for the predicted implant power of each formula were constructed and differences between predicted results of the formulas were plotted. MAIN OUTCOME MEASURE: Predicted implant power. RESULTS: Significant differences in intraocular lens power prediction were found among the Hoffer Q, Holladay I, and SRK II formulas in the pediatric range of axial length and keratometry values. The Holladay I and Haigis formulas were found to be similar in their intraocular lens power prediction. The SRK/T was comparable with the Holladay I and Haigis formulas, but still differed in the high keratometry values. CONCLUSIONS: This analysis demonstrates differences in the intraocular lens power prediction among commonly used formulas for axial length and keratometry values in the pediatric range. It is unclear under what circumstances each of these formulas may be preferred in the pediatric population.

Intraocular lens power calculation in children.

With improving surgical technique and equipment, the acceptable age for placing an intraocular lens in infants and children is becoming younger. The tools for predicting intraocular lens power have not necessarily kept up, as current theoretical and regression intraocular lens power prediction formulas are largely based on adult eyes at axial lengths, anterior chamber depth, and keratometric values much different than those seen in infants. In addition, the adult eye has matured and is no longer growing, whereas the eyes of infants and children may continue to note changes in axial length, keratometric values, and possibly optical characteristics. Another source of error in intraocular lens power selection that is more likely to occur in pediatric patients than in adult patients is inaccuracy in measurement of axial length or keratometric power. A review of current tools and considerations for intraocular lens power prediction in infants and children is presented.

Cataracts in congenital toxoplasmosis.

PURPOSE: To determine the incidence and natural history of cataracts in children with congenital toxoplasmosis. METHODS: Children referred to the National Collaborative Chicago-based Congenital Toxoplasmosis Study (NCCCTS) between 1981 and 2005 were examined by ophthalmologists at predetermined times according to a specific protocol. The clinical course and treatment of patients who developed cataracts were reviewed. RESULTS: In the first year of life, 134 of 173 children examined were treated with pyrimethamine, sulfadiazine, and leukovorin, while the remaining 39 were not treated. Cataracts occurred in 27 eyes of 20 patients (11.6%, 95% confidence interval [7.2%, 17.3%]). Fourteen cataracts were present at birth and 13 developed postnatally. Locations of the cataracts included anterior polar (three eyes), anterior subcapsular (six eyes), nuclear (five eyes), posterior subcapsular (seven eyes), and unknown (six eyes). Thirteen cataracts were partial, nine total, and five with unknown complexity. Twelve cataracts remained stable, 12 progressed, and progression was not known for 3. Five of 27 eyes had cataract surgery, with 2 of these developing glaucoma. Sixteen eyes of 11 patients had retinal detachment and cataract. All eyes with cataracts had additional ocular lesions. CONCLUSIONS: In the NCCCTS cohort, 11.6% of patients were diagnosed with cataracts. There was considerable variability in the presentation, morphology, and progression of the cataracts. Associated intraocular pathology was an important cause of morbidity.

Enlargement of the superior rectus and superior oblique muscles causes intorsion in Graves' eye disease.

PURPOSE: To review the prevalence of preoperative and postoperative intorsion in patients with strabismus and Graves' eye disease (GED), and to correlate the intorsion with coexisting superior rectus (SR) and superior oblique (SO) muscle enlargement as a possible mechanism causing intorsion in these patients. METHODS: Charts of consecutive patients with GED who underwent strabismus surgery between 1 January 2010 and 1 April 2013 were retrospectively reviewed. Of these, patients with orbital CT or MRI scan were identified for further analysis. Clinical characteristics documented included age, gender, horizontal and vertical deviation, subjective torsional deviation, specific extraocular muscles (EOMs) operated upon, EOM enlargement on CT/MRI scans and width and thickness of SO, SR group and inferior rectus (IR). RESULTS: Charts of 45 patients (14 males and 31 females) were reviewed. Mean age was 56.8±12.5 years. Of these, seven (15.6%) patients demonstrated intorsion, and 38 (84.4%) patients demonstrated extorsion preoperatively. But after strabismus surgery, 15 (39.5%) of the 38 patients with preoperative extorsion demonstrated postoperative intorsion and 23 (60.5%) patients continued to show postoperative extorsion. On analysis of CT/MRI scans in these patients, only an increase in the thickness of SR group and the thickness/width of SO muscle were significantly associated with preoperative and postoperative intorsion; while age, gender, preoperative horizontal or vertical deviation and IR recession were unrelated to preoperative or postoperative intorsion. Postoperative intorsion was also associated with smaller degrees of preoperative extorsion (<3.5°). CONCLUSIONS: Preoperative SR and/or SO muscle enlargement appear to be a primary contributing factor relating to preoperative and postoperative intorsion in patients with GED-associated strabismus. Patients with only small amounts of preoperative extorsion (<3.5°) in the presence of tight IRs should be carefully evaluated for possible SR and/or SO involvement by CT or MRI scan to predict those at risk for and plan for prevention/treatment of postoperative intorsion.

Social and emotional impact of strabismus surgery on quality of life in children.

PURPOSE: Improved quality of life after strabismus surgery has been demonstrated in adults, but has not been extensively studied in children. The purpose of this study was to evaluate the psychosocial effects of childhood strabismus surgery. METHODS: This was a prospective interventional study. A modified version of the RAND Health Insurance Study quality of life instrument was administered to parents or guardians of children with strabismus. The questionnaire was administered by telephone interviews conducted by trained staff before and 2 months after corrective surgery. RESULTS: Ninety-eight children with a mean age of 4.5 (+/-3.3) years were studied. Reliability measures (Cronbach's alpha coefficients) indicate that the questionnaire has good internal consistency (alpha > 0.7 in most subscales). Compared with before surgery, significant improvements were noted after surgery, especially within the functional limitations (paired Student's t -test, P = 0.01), social relations ( P < 0.01), general health perceptions ( P < 0.01), and developmental satisfaction ( P < 0.01) subscales. CONCLUSIONS: Parental proxies can provide meaningful measures of children's response to strabismus surgery. Statistically significant improvements were observed in social, emotional, and functional measures of the children's health status. As previously documented for adults, this study shows that psychosocial benefits afforded by strabismus surgery also contribute to an improvement in quality of life for children.

CFEOM1, the classic familial form of congenital fibrosis of the extraocular muscles, is genetically heterogeneous but does not result from mutations in ARIX.

BACKGROUND: To learn about the molecular etiology of strabismus, we are studying the genetic basis of 'congenital fibrosis of the extraocular muscles' (CFEOM). These syndromes are characterized by congenital restrictive ophthalmoplegia affecting muscles in the oculomotor and trochlear nerve distribution. Individuals with the classic form of CFEOM are born with bilateral ptosis and infraducted globes. When all affected members of a family have classic CFEOM, we classify the family as a CFEOM1 pedigree. We have previously determined that a CFEOM1 gene maps to the FEOM1 locus on chromosome 12cen. We now identify additional pedigrees with CFEOM1 to determine if the disorder is genetically heterogeneous and, if so, if any affected members of CFEOM1 pedigrees or sporadic cases of classic CFEOM harbor mutations in ARIX, the CFEOM2 disease gene. RESULTS: Eleven new CFEOM1 pedigrees were identified. All demonstrated autosomal dominant inheritance, and nine were consistent with linkage to FEOM1. Two small CFEOM1 families were not linked to FEOM1, and both were consistent with linkage to FEOM3. We screened two CFEOM1 families consistent with linkage to FEOM2 and 5 sporadic individuals with classic CFEOM and did not detect ARIX mutations. CONCLUSIONS: The phenotype of two small CFEOM1 families does not map to FEOM1, establishing genetic heterogeneity for this disorder. These two families may harbor mutations in the FEOM3 gene, as their phenotype is consistent with linkage to this locus. Thus far, we have not identified ARIX mutations in any affected members of CFEOM1 pedigrees or in any sporadic cases of classic CFEOM.