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Phenotypic Spectrum of FZD4 Mutations
92
Abstracts
Phenotypic Spectrum of FZD4 Mutations Johane M. Robitaille MD, Binyou Zheng MD, Karen Wallace, Mark Samuels PhD, Jill Beis, Duane Guernsey PhD; Dalhousie University, Halifax, Nova Scotia, Canada Introduction: The Wnt pathway was recently implicated in cases of familial exudative vitreoretinopathy (FEVR). In 2002, we identified the first mutated gene in this pathway, FZD4, causing a human disease in a large family with the autosomal-dominant form of FEVR. Since this discovery, we have been interested in describing the full range of the phenotype caused by FZD4 mutations, including testing for genotype–phenotype associations. Methods: Patients with clinical features within the phenotypic spectrum of FEVR were invited to participate. DNA was used for direct sequencing of the coding regions of the two FZD4 exons. Phenotypic information was acquired from eye examination or chart review. Results: Two separate pedigrees were identified with distinct causal mutations: one with a M493_W494del, and the other with a I114T missense mutation. The proband in each pedigree had severe bilateral fundus anomalies consisting of an optic nerve fibrovascular stalk with attachments to the inferotemporal lens and retinal dysplasia. Other family members carrying the same mutation within each of these pedigrees were asymptomatic with minimal fundus anomalies. Discussion: FZD4 mutations can be associated with retinal dysplasia and features that overlap with posterior persistent hyperplastic primary vitreous (PHPV). This severe phenotype is not mutation specific, as other family members with the same mutation can manifest the mildest form of FEVR. Conclusions: Bilateral posterior PHPVlike features are part of the FEVR spectrum and, in the absence of a family history, this phenotype should prompt screening of the parents and siblings for clinical and molecular identifiers of FEVR. Standard Strabismus Surgery in Thyroid Ophthalmopathy Leemor B. Rotberg MD, Derek T. Sprunger MD, Naval Sondhi MD; Indiana University, Indianapolis, Indiana Introduction: Techniques for the surgical treatment of thyroidrelated strabismus are varied and include nonadjustable (standard) and adjustable sutures. This study reports results from one clinical practice utilizing standard strabismus procedures for treatment of thyroid ophthalmopathy. Methods: The charts of 32 consecutive patients who underwent surgery in the past 5 years for restrictive strabismus secondary to thyroid ophthalmopathy were retrospectively reviewed. All surgeries were performed by reattachment of the muscle to the globe, allowing for no postoperative adjustment (standard technique). Results: All 32 patients had preoperative diplopia and restricted motility. Twenty-two patients wore prisms prior to surgery. Of the 32 patients who underwent surgery, 9 required a second operation. After reoperation five patients (12%) continued to have diplopia; however, four of these patients were able to achieve single binocular vision with prism. Only one patient was unable to achieve single binocular vision with or without prism. Twenty-two (54%) had full motility after surgery. After one surgery, 25 of 32 patients (78%) were satisfied with the visual results of surgery. This increased to 31 patients (97%) after reoperation. Discussion: There is disagreement as to which technique (adjustable versus standard) has a better surgical outcome. This was not a comparative study, but meant to present the results of one clinical practice with standard techniques. Strabismus surgery with adjustable sutures can potentially be uncomfortable and produce late overcorrection. In our study, strabismus surgery by standard techniques provided excellent postoperative results with a 97% satisfaction rate. Conclusion: The results of the study indicate that strabismus surgery for restrictive thyroid ophthalmopathy using standard techniques can provide excellent results and patient satisfaction.
Journal of AAPOS Volume 10 Number 1 February 2006 Effect of Patient Characteristics on Retinal Nerve Fiber Layer Thickness in Children Daniel J. Salchow, Lama A. Al-Aswad, Michael F. Chiang, Yuri Oleynikov, Elliott Kanner, James C. Tsai; Children’s National Medical Center, Washington, DC Purpose: To analyze the effect of patient characteristics on peripapillary retinal nerve fiber layer (RNFL) thickness in children. Methods: RNFL thickness was measured using StratusOCT in 179 eyes of 92 (age 4 to 17 years) with normal optic discs. The effect of age, refraction, gender, laterality (right versus left eyes), scan quality, and cooperation on RNFL thickness measurements was analyzed statistically. Results: Average RNFL thickness for all eyes was 107.0 ⫾ 10.7 m (range 78.1 to 128.4 m). Age (P ⫽ 0.018) and refraction (P ⫽ 0.001) had a statistically significant effect on RNFL thickness. Gender, laterality, scan quality, and cooperation did not have a significant effect. In addition, age had a statistically significant effect on refraction (P ⫽ 0.001). Conclusions: Age and refraction have a statistically significant effect on RNFL thickness in children. Age appears to be the more important variable, as it had a statistically significant effect on refraction in our study group. Complications of Pediatric Cataract-Intraocular Lens Implantation Leslie Scarlett MD, M. Edward Wilson Jr MD, Rupal H. Trivedi MD, John French; Storm Eye Institute, Medical University of South Carolina, Charleston, SC Purpose: Intraocular lens (IOL) implantation has become accepted practice for select children beyond their first birthday. We report the anatomical outcomes of IOL implantation in children. Methods: Retrospective chart review of pediatric cataract surgery cases with primary IOL implantation performed by a single surgeon. Eyes with traumatic cataract, uveitis, aniridia, lens subluxation, aphakia, and secondary IOL were excluded. Results: Two hundred eighty-nine eyes fit our inclusion criteria. Average age at surgery and follow-up was 5.2 (SD 4.6) and 3.2 (SD 2.8) years, respectively. Type of IOL was predominantly hydrophobic acrylic (215) and PMMA (58). Primary posterior capsulectomy and vitrectomy (PC⫹V) was performed in 73.4% of the eyes. In-the-bag implantation was achieved in 88.6% of the eyes. Postoperative glaucoma was noted in nine eyes, all operated before the child’s first birthday (P ⬍.001, Fisher’s exact test). Treatment for visual axis opacification (VAO) was required in 40 eyes at a mean of 12.8 (SD 10.9) months after cataract surgery. Treatment for VAO was required in 20/76 (26.3%) eyes when the posterior capsule was left intact at the time of surgery, and 20/213 (9.4%) eyes when PC⫹V was undertaken at the time of surgery (P ⫽ 0.001, 2 test). Fifteen of 67 eyes (22.4%) receiving PC⫹V before the child’s first birthday, and 5 of 145 eyes receiving PC⫹V (3.5%) beyond the first birthday, required secondary surgery to remove the VAO. Median age of these latter five patients was 1.2 years. Single events of dislocated IOL, synechiolysis, and resuturing because of a broken suture were noted. Conclusion: IOL implantation with primary posterior capsulectomy and vitrectomy provided a satisfactory outcome in children especially beyond their first birthday.
Abstracts
Phenotypic Spectrum of FZD4 Mutations Johane M. Robitaille MD, Binyou Zheng MD, Karen Wallace, Mark Samuels PhD, Jill Beis, Duane Guernsey PhD; Dalhousie University, Halifax, Nova Scotia, Canada Introduction: The Wnt pathway was recently implicated in cases of familial exudative vitreoretinopathy (FEVR). In 2002, we identified the first mutated gene in this pathway, FZD4, causing a human disease in a large family with the autosomal-dominant form of FEVR. Since this discovery, we have been interested in describing the full range of the phenotype caused by FZD4 mutations, including testing for genotype–phenotype associations. Methods: Patients with clinical features within the phenotypic spectrum of FEVR were invited to participate. DNA was used for direct sequencing of the coding regions of the two FZD4 exons. Phenotypic information was acquired from eye examination or chart review. Results: Two separate pedigrees were identified with distinct causal mutations: one with a M493_W494del, and the other with a I114T missense mutation. The proband in each pedigree had severe bilateral fundus anomalies consisting of an optic nerve fibrovascular stalk with attachments to the inferotemporal lens and retinal dysplasia. Other family members carrying the same mutation within each of these pedigrees were asymptomatic with minimal fundus anomalies. Discussion: FZD4 mutations can be associated with retinal dysplasia and features that overlap with posterior persistent hyperplastic primary vitreous (PHPV). This severe phenotype is not mutation specific, as other family members with the same mutation can manifest the mildest form of FEVR. Conclusions: Bilateral posterior PHPVlike features are part of the FEVR spectrum and, in the absence of a family history, this phenotype should prompt screening of the parents and siblings for clinical and molecular identifiers of FEVR. Standard Strabismus Surgery in Thyroid Ophthalmopathy Leemor B. Rotberg MD, Derek T. Sprunger MD, Naval Sondhi MD; Indiana University, Indianapolis, Indiana Introduction: Techniques for the surgical treatment of thyroidrelated strabismus are varied and include nonadjustable (standard) and adjustable sutures. This study reports results from one clinical practice utilizing standard strabismus procedures for treatment of thyroid ophthalmopathy. Methods: The charts of 32 consecutive patients who underwent surgery in the past 5 years for restrictive strabismus secondary to thyroid ophthalmopathy were retrospectively reviewed. All surgeries were performed by reattachment of the muscle to the globe, allowing for no postoperative adjustment (standard technique). Results: All 32 patients had preoperative diplopia and restricted motility. Twenty-two patients wore prisms prior to surgery. Of the 32 patients who underwent surgery, 9 required a second operation. After reoperation five patients (12%) continued to have diplopia; however, four of these patients were able to achieve single binocular vision with prism. Only one patient was unable to achieve single binocular vision with or without prism. Twenty-two (54%) had full motility after surgery. After one surgery, 25 of 32 patients (78%) were satisfied with the visual results of surgery. This increased to 31 patients (97%) after reoperation. Discussion: There is disagreement as to which technique (adjustable versus standard) has a better surgical outcome. This was not a comparative study, but meant to present the results of one clinical practice with standard techniques. Strabismus surgery with adjustable sutures can potentially be uncomfortable and produce late overcorrection. In our study, strabismus surgery by standard techniques provided excellent postoperative results with a 97% satisfaction rate. Conclusion: The results of the study indicate that strabismus surgery for restrictive thyroid ophthalmopathy using standard techniques can provide excellent results and patient satisfaction.
Journal of AAPOS Volume 10 Number 1 February 2006 Effect of Patient Characteristics on Retinal Nerve Fiber Layer Thickness in Children Daniel J. Salchow, Lama A. Al-Aswad, Michael F. Chiang, Yuri Oleynikov, Elliott Kanner, James C. Tsai; Children’s National Medical Center, Washington, DC Purpose: To analyze the effect of patient characteristics on peripapillary retinal nerve fiber layer (RNFL) thickness in children. Methods: RNFL thickness was measured using StratusOCT in 179 eyes of 92 (age 4 to 17 years) with normal optic discs. The effect of age, refraction, gender, laterality (right versus left eyes), scan quality, and cooperation on RNFL thickness measurements was analyzed statistically. Results: Average RNFL thickness for all eyes was 107.0 ⫾ 10.7 m (range 78.1 to 128.4 m). Age (P ⫽ 0.018) and refraction (P ⫽ 0.001) had a statistically significant effect on RNFL thickness. Gender, laterality, scan quality, and cooperation did not have a significant effect. In addition, age had a statistically significant effect on refraction (P ⫽ 0.001). Conclusions: Age and refraction have a statistically significant effect on RNFL thickness in children. Age appears to be the more important variable, as it had a statistically significant effect on refraction in our study group. Complications of Pediatric Cataract-Intraocular Lens Implantation Leslie Scarlett MD, M. Edward Wilson Jr MD, Rupal H. Trivedi MD, John French; Storm Eye Institute, Medical University of South Carolina, Charleston, SC Purpose: Intraocular lens (IOL) implantation has become accepted practice for select children beyond their first birthday. We report the anatomical outcomes of IOL implantation in children. Methods: Retrospective chart review of pediatric cataract surgery cases with primary IOL implantation performed by a single surgeon. Eyes with traumatic cataract, uveitis, aniridia, lens subluxation, aphakia, and secondary IOL were excluded. Results: Two hundred eighty-nine eyes fit our inclusion criteria. Average age at surgery and follow-up was 5.2 (SD 4.6) and 3.2 (SD 2.8) years, respectively. Type of IOL was predominantly hydrophobic acrylic (215) and PMMA (58). Primary posterior capsulectomy and vitrectomy (PC⫹V) was performed in 73.4% of the eyes. In-the-bag implantation was achieved in 88.6% of the eyes. Postoperative glaucoma was noted in nine eyes, all operated before the child’s first birthday (P ⬍.001, Fisher’s exact test). Treatment for visual axis opacification (VAO) was required in 40 eyes at a mean of 12.8 (SD 10.9) months after cataract surgery. Treatment for VAO was required in 20/76 (26.3%) eyes when the posterior capsule was left intact at the time of surgery, and 20/213 (9.4%) eyes when PC⫹V was undertaken at the time of surgery (P ⫽ 0.001, 2 test). Fifteen of 67 eyes (22.4%) receiving PC⫹V before the child’s first birthday, and 5 of 145 eyes receiving PC⫹V (3.5%) beyond the first birthday, required secondary surgery to remove the VAO. Median age of these latter five patients was 1.2 years. Single events of dislocated IOL, synechiolysis, and resuturing because of a broken suture were noted. Conclusion: IOL implantation with primary posterior capsulectomy and vitrectomy provided a satisfactory outcome in children especially beyond their first birthday.