- Email: [email protected]
Ophthalmic Findings in Apert Syndrome Prior to Craniofacial Surgery
moderate or severe glaucoma. In addition, it cannot be excluded that the 24-hour rhythm of aqueous melatonin differs in glaucoma patients and in normal subjects. To confirm this possibility, further studies are needed in nonhuman primates over a 24-hour cycle. The reduction of IOP5,6 could possibly be mediated via melatonin receptors (as MT3 receptor) located in the eye, in the anterior segment,7 or in the ciliary body.5
To determine ophthalmic findings in patients with Apert syndrome before craniofacial surgery. DESIGN: A cross-sectional retrospective study. METHODS: Review of 63 cases (27 males, 36 females) with Apert syndrome without craniofacial surgery from the Australian Craniofacial Unit. Demographic data, age of presentation, and ophthalmic findings at the first presentation were recorded. RESULTS: At a mean age of four years and median age of one year, at least 14% of patients had amblyopia, 60% of patients had strabismus, 19% of patients had anisometropia, and 34% of eyes had ametropia. Exposure keratopathy and corneal scarring occurred in at least 13% of patients and optic atrophy in at least 8% of patients. CONCLUSIONS: This study demonstrated that patients with Apert syndrome were at risk of amblyopia because of high prevalence of refractive errors, strabismus, and anisometropia. Exposure keratopathy and corneal scarring occurred commonly. (Am J Ophthalmol 2006;142: 328 –330. © 2006 by Elsevier Inc. All rights reserved.) PURPOSE:
REFERENCES
1. Liu JH, Dacus AC. Endogenous hormonal changes and circadian elevation of intraocular pressure. Invest Ophthalmol Vis Sci 1991;32:496 –500. 2. Martin XD, Malina HZ, Brennan MC, Hendrickson PH, Lichter PR. The ciliary body—the third organ found to synthesize indoleamines in humans. Eur J Ophthalmol 1992; 2:67–72. 3. Yu HS, Yee RW, Howes KA, Reiter RJ. Diurnal rhythms of immunoreactive melatonin in the aqueous humor and serum of male pigmented rabbits. Neurosci Lett 1990;116: 309 –314. 4. Rohde BH, Chiou GC. Is ocular melatonin regulated by the adrenergic system? Ophthalmic Res 1987;19:178 –186. 5. Wiechmann AF, Wirsig-Wiechmann CR. Melatonin receptor mRNA and protein expression in Xenopus laevis nonpigmented ciliary epithelial cells. Exp Eye Res 2001;73: 617– 623. 6. Serle JB, Wang RF, Peterson WM, Plourde R, Yerxa BR. Effect of 5-MCA-NAT, a putative melatonin MT3 receptor agonist, on intraocular pressure in glaucomatous monkey eyes. J Glaucoma 2004;13:385–388. 7. Meyer P, Pache M, Loeffler KU, et al. Melatonin MT-1receptor immunoreactivity in the human eye. Br J Ophthalmol 2002;86:1053–1057.
A
PERT SYNDROME IS A WELL RECOGNIZED CRANIOSYN-
ostosis syndrome characterized by craniosynostosis, midfacial hypoplasia, and syndactyly of the hands and feet1
Ophthalmic Findings in Apert Syndrome Prior to Craniofacial Surgery Jwu Jin Khong, MBBS (Hons), Peter Anderson, MD, Timothy L. Gray, MBBS, Michael Hammerton, FRANZCO, Dinesh Selva, FRANZCO, and David David, MD
Accepted for publication Feb 21, 2006. From the Oculoplastic and Orbital Division, Department of Ophthalmology and Visual Sciences, University of Adelaide, Adelaide, Australia (J.J.K., D.S.); the Australian Craniofacial Unit, Women’s and Children’s Hospital, North Adelaide, Australia (P.A., M.H., D.D.); the Department of Physiology and Pharmacology, Lions Eye Institute, Nedlands, Australia (T.L.G.); the Harley Eye Clinic, North Adelaide, Australia (M.H.); and the Australian Craniofacial Unit Institute, associated with the University of Adelaide, North Adelaide, Australia (D.D.). Inquiries to Jwu Jin Khong, MBBS (Hons), Royal Adelaide Hospital, Department of Ophthalmology and Visual Science, North Terrace, Adelaide, SA 5000, Australia; e-mail: [email protected]
328
AMERICAN JOURNAL
FIGURE 1. Preoperative features of Apert syndrome showing turricephaly, midface hypoplasia with shallow orbits, proptosis, down slanting palpebral fissure, and hypoplastic upper jaw with class III malocclusion.
OF
OPHTHALMOLOGY
AUGUST 2006
FIGURE 2. Syndactyly of the hands and feet is a universal finding in Apert syndrome. (Left) syndactyly of the hands. (Right) syndactyly of the feet.
TABLE. Ophthalmic Findings in Apert Syndrome at Presentation
Ophthalmic Findings
Visual impairment ⬍6/12 in better eye Visual impairment ⬍6/12 in at least one eye Refractive errors Hypermetropia Myopia Emmetropia Astigmatism Anisometropia Strabismus Type of strabismus Exotropia Esotropia Vertical Exophoria Manifest unspecified Amblyopia Optic atrophy Optic disk swelling Abnormal VEP Corneal scar and exposure keratopathy Proptosis Ptosis
No. With Positive Finding (n)
3 7 30 13 45 37 12 38 21 11 3 2 1 9 5 3 9 8 55 14
Data Available
16 cases 16 cases 88 eyes
Occurrence as Percentages of Available Data
Occurrence as Percentages of Total (n ⫽ 63 cases ⫽ 126 eyes)
3/16 (19%) 7/16 (44%)
3/63 (5%) 7/63 (11%)
44 cases 58 cases
30/88 (34%) 13/88 (15%) 45/88 (51%) 37/88 (42%) 12/44 (27%) 38/58 (66%)
30/126 (24%) 13/126 (10%) 45/126 (36%) 37/126 (29%) 12/63 (19%) 38/63 (60%)
49 60 60 42 59 60 44
21/58 (36%) 11/58 (19%) 3/58 (5%) 2/58 (3%) 1/58 (2%) 9/49 (18%) 5/60 (8%) 3/60 (5%) 9/42 (21%) 8/59 (14%) 55/60 (92%) 14/44 (32%)
21/63 (33%) 11/63 (17%) 3/63 (5%) 2/63 (3%) 1/63 (2%) 9/63 (14%) 5/63 (8%) 3/63 (5%) 9/63 (14%) 8/63 (13%) 55/63 (87%) 14/63 (22%)
cases cases cases cases cases cases cases
VEP ⫽ visual evoked potentials.
(Figures 1 and 2). Visual loss is a severe complication of Apert syndrome, which could result from optic atrophy, amblyopia, and exposure corneal scarring.2,3 Absence or structural alteration of extraocular muscles, iris coloboma, cataract, ocular albinism, keratoconus, ectopia lentis, and medullated nerve fibers had also been reported with this syndrome.2– 6 However, most publications either described VOL. 142, NO. 2
case reports or small series of Apert syndrome or findings of combined craniosynostoses. The aim of this study was to determine the prevalence of ophthalmic findings in Apert syndrome before craniofacial surgery in a large series of patients. Retrospective reviews of 87 patients diagnosed with Apert syndrome from 1975 to 2004 were identified from
BRIEF REPORTS
329
the Australian Craniofacial Unit database. Ethics approval was obtained from institutional review board taking into consideration that informed consent was not possible for patients living overseas. Patients who had craniofacial surgery before their first presentation were excluded. Sixtythree cases (27 males and 36 females) were therefore included in the study. The mean age at first presentation was four years (range 0.1 to 39.2 years, SD 8.21) and the median age was one year. The parameters investigated included visual acuity, cycloplegic refraction, amblyopia, strabismus, anterior segment findings, funduscopic findings, and visual evoked potentials (VEP). Because of the retrospective nature of this study, not all data were present for all parameters: 16 notes contained Snellen visual acuity, 44 had data on cycloplegic refraction, 58 had data on strabismus, 49 had data on amblyopia, 59 had documented anterior segment findings, 60 had documented fundus findings, and 42 had data on VEP. There were at least three patients (5%) with visual impairment worse than 6/12 in the better eye, and at least seven patients (11%) with visual impairment in at least one eye. At least nine patients (14%) had amblyopia. Strabismus was noted in at least 38 patients (60%) of the study population. Exotropia was more common than esotropia (21 patients compared with 11 patients). At least 30 eyes (24%) had hypermetropia ⱖ⫹2 diopters (D), 13 eyes (10%) had myopia ⱕ⫺0.5 diopters, and 37 eyes (29%) had astigmatism ⱖ0.75 diopters. In addition, at least 12 patients (19%) had anisometropia ⱖ0.75 diopters. Fundoscopy revealed optic atrophy in at least five patients (8%), and optic disk edema in three patients (5%). At least nine patients (14%) had abnormal VEP, four bilaterally. Latency was prolonged in six cases while the amplitude was suppressed in three cases. Only two of the nine cases with VEP abnormality had optic atrophy and disk edema. Proptosis was present in at least 55 patients (87%), and corneal scarring and exposure keratopathy were present in at least eight patients (13%). Ptosis (marginal reflex distance ⬍3 mm) was present in at least 14 patients (22%), two were unilateral, and 12 were bilateral (Table). Other notable ophthalmic findings included bilateral myelinated optic nerve fibers (one), entropion (one), epiblepharon (two), trichiasis (two), coloboma of the disk (two), and tortuous retinal vessels (one). This is the largest study reported looking at ophthalmic findings in Apert syndrome before craniofacial intervention. We found that patients with Apert Syndrome were at risk of amblyopia because of high prevalence of refractive errors, anisometropia, and strabismus. Our study is in agreement with earlier studies, which showed that exotropia was more common than esotropia in Apert syndrome.3,4 These patients need regular ophthalmic evaluation for early detection of amblyopia to institute 330
AMERICAN JOURNAL
timely management. Our study also found that exposure keratopathy and corneal scarring occurred commonly. Invariably exposure keratopathy was attributable to inadequate lubrication and lid protection secondary to proptosis.2,3,7 The extent of visual impairment and amblyopia could be better assessed by a prospective study following the cohort through to visual maturation. REFERENCES
1. Cohen MM Jr, Kreiborg S. A clinical study of the craniofacial features in Apert syndrome. Int J Oral Maxillofac Surg 1996;25:45–53. 2. Miller MT. Ocular findings in craniosynostosis. In: Cohen MM Jr, editor. Craniosynostosis, diagnosis, evaluation, and management. 2nd ed. New York: Raven, 1996:184 –194. 3. Buncic JR. Ocular aspects of Apert syndrome. Clin Plast Surg 1991;18:315–319. 4. Hertle RW, Quinn GE, Minguini N, et al. Visual loss in patients with craniofacial synostosis. J Pediatr Ophthalmol Strabismus 1991;28:344 –349. 5. Pollard ZF. Bilateral superior oblique muscle palsy associated with Apert syndrome. Am J Ophthalmol 1988;106:337–340. 6. Margolis S, Pachter BR, Breinin GM. Structural alterations of extraocular muscle associated with Apert syndrome. Br J Ophthalmol 1977;61:683– 689. 7. Ueeck B, Le B, Goodman S, et al. Corneal ulcers in patients with Apert syndrome. J Craniofacial Surg 2001;12:134 –135.
Pigment Release and Secondary Glaucoma After Implantation of Single-piece Acrylic Intraocular Lenses in the Ciliary Sulcus Harvey Siy Uy, MD, and Pik Sha T. Chan, MD PURPOSE: To report the association of sulcus-fixated, single-
piece hydrophobic acrylic intraocular lenses (HAIOL) with pigment release and secondary glaucoma. DESIGN: Interventional case series. METHODS: HAIOL was implanted in the ciliary sulcus of 20 eyes that developed posterior capsule rupture during phacoemulsification. We analyzed postoperative bestcorrected visual acuity, manifest refraction, frequency of intraocular lens malpositioning, and postoperative complications. RESULTS: Postoperative best-corrected visual acuity was 20/40 or better in all eyes. The mean postoperative sphere was ⴚ0.5 ⴞ 0.7 diopters (range ⴙ1.25 to ⴚ2.00); the mean postoperative cylinder was ⴚ1.2 ⴞ Accepted for publication Feb 23, 2006. From the University of the Philippines, Philippine General Hospital (H.S.U.), Manila, and Asian Eye Institute (H.S.U., P.S.T.C.), Makati City, Philippines. Inquiries to Harvey Siy Uy, MD, Asian Eye Institute, 9F Phinma Plaza Building, Rockwell Center, Makati City, Philippines 1200; e-mail: [email protected] OF
OPHTHALMOLOGY
AUGUST 2006
To determine ophthalmic findings in patients with Apert syndrome before craniofacial surgery. DESIGN: A cross-sectional retrospective study. METHODS: Review of 63 cases (27 males, 36 females) with Apert syndrome without craniofacial surgery from the Australian Craniofacial Unit. Demographic data, age of presentation, and ophthalmic findings at the first presentation were recorded. RESULTS: At a mean age of four years and median age of one year, at least 14% of patients had amblyopia, 60% of patients had strabismus, 19% of patients had anisometropia, and 34% of eyes had ametropia. Exposure keratopathy and corneal scarring occurred in at least 13% of patients and optic atrophy in at least 8% of patients. CONCLUSIONS: This study demonstrated that patients with Apert syndrome were at risk of amblyopia because of high prevalence of refractive errors, strabismus, and anisometropia. Exposure keratopathy and corneal scarring occurred commonly. (Am J Ophthalmol 2006;142: 328 –330. © 2006 by Elsevier Inc. All rights reserved.) PURPOSE:
REFERENCES
1. Liu JH, Dacus AC. Endogenous hormonal changes and circadian elevation of intraocular pressure. Invest Ophthalmol Vis Sci 1991;32:496 –500. 2. Martin XD, Malina HZ, Brennan MC, Hendrickson PH, Lichter PR. The ciliary body—the third organ found to synthesize indoleamines in humans. Eur J Ophthalmol 1992; 2:67–72. 3. Yu HS, Yee RW, Howes KA, Reiter RJ. Diurnal rhythms of immunoreactive melatonin in the aqueous humor and serum of male pigmented rabbits. Neurosci Lett 1990;116: 309 –314. 4. Rohde BH, Chiou GC. Is ocular melatonin regulated by the adrenergic system? Ophthalmic Res 1987;19:178 –186. 5. Wiechmann AF, Wirsig-Wiechmann CR. Melatonin receptor mRNA and protein expression in Xenopus laevis nonpigmented ciliary epithelial cells. Exp Eye Res 2001;73: 617– 623. 6. Serle JB, Wang RF, Peterson WM, Plourde R, Yerxa BR. Effect of 5-MCA-NAT, a putative melatonin MT3 receptor agonist, on intraocular pressure in glaucomatous monkey eyes. J Glaucoma 2004;13:385–388. 7. Meyer P, Pache M, Loeffler KU, et al. Melatonin MT-1receptor immunoreactivity in the human eye. Br J Ophthalmol 2002;86:1053–1057.
A
PERT SYNDROME IS A WELL RECOGNIZED CRANIOSYN-
ostosis syndrome characterized by craniosynostosis, midfacial hypoplasia, and syndactyly of the hands and feet1
Ophthalmic Findings in Apert Syndrome Prior to Craniofacial Surgery Jwu Jin Khong, MBBS (Hons), Peter Anderson, MD, Timothy L. Gray, MBBS, Michael Hammerton, FRANZCO, Dinesh Selva, FRANZCO, and David David, MD
Accepted for publication Feb 21, 2006. From the Oculoplastic and Orbital Division, Department of Ophthalmology and Visual Sciences, University of Adelaide, Adelaide, Australia (J.J.K., D.S.); the Australian Craniofacial Unit, Women’s and Children’s Hospital, North Adelaide, Australia (P.A., M.H., D.D.); the Department of Physiology and Pharmacology, Lions Eye Institute, Nedlands, Australia (T.L.G.); the Harley Eye Clinic, North Adelaide, Australia (M.H.); and the Australian Craniofacial Unit Institute, associated with the University of Adelaide, North Adelaide, Australia (D.D.). Inquiries to Jwu Jin Khong, MBBS (Hons), Royal Adelaide Hospital, Department of Ophthalmology and Visual Science, North Terrace, Adelaide, SA 5000, Australia; e-mail: [email protected]
328
AMERICAN JOURNAL
FIGURE 1. Preoperative features of Apert syndrome showing turricephaly, midface hypoplasia with shallow orbits, proptosis, down slanting palpebral fissure, and hypoplastic upper jaw with class III malocclusion.
OF
OPHTHALMOLOGY
AUGUST 2006
FIGURE 2. Syndactyly of the hands and feet is a universal finding in Apert syndrome. (Left) syndactyly of the hands. (Right) syndactyly of the feet.
TABLE. Ophthalmic Findings in Apert Syndrome at Presentation
Ophthalmic Findings
Visual impairment ⬍6/12 in better eye Visual impairment ⬍6/12 in at least one eye Refractive errors Hypermetropia Myopia Emmetropia Astigmatism Anisometropia Strabismus Type of strabismus Exotropia Esotropia Vertical Exophoria Manifest unspecified Amblyopia Optic atrophy Optic disk swelling Abnormal VEP Corneal scar and exposure keratopathy Proptosis Ptosis
No. With Positive Finding (n)
3 7 30 13 45 37 12 38 21 11 3 2 1 9 5 3 9 8 55 14
Data Available
16 cases 16 cases 88 eyes
Occurrence as Percentages of Available Data
Occurrence as Percentages of Total (n ⫽ 63 cases ⫽ 126 eyes)
3/16 (19%) 7/16 (44%)
3/63 (5%) 7/63 (11%)
44 cases 58 cases
30/88 (34%) 13/88 (15%) 45/88 (51%) 37/88 (42%) 12/44 (27%) 38/58 (66%)
30/126 (24%) 13/126 (10%) 45/126 (36%) 37/126 (29%) 12/63 (19%) 38/63 (60%)
49 60 60 42 59 60 44
21/58 (36%) 11/58 (19%) 3/58 (5%) 2/58 (3%) 1/58 (2%) 9/49 (18%) 5/60 (8%) 3/60 (5%) 9/42 (21%) 8/59 (14%) 55/60 (92%) 14/44 (32%)
21/63 (33%) 11/63 (17%) 3/63 (5%) 2/63 (3%) 1/63 (2%) 9/63 (14%) 5/63 (8%) 3/63 (5%) 9/63 (14%) 8/63 (13%) 55/63 (87%) 14/63 (22%)
cases cases cases cases cases cases cases
VEP ⫽ visual evoked potentials.
(Figures 1 and 2). Visual loss is a severe complication of Apert syndrome, which could result from optic atrophy, amblyopia, and exposure corneal scarring.2,3 Absence or structural alteration of extraocular muscles, iris coloboma, cataract, ocular albinism, keratoconus, ectopia lentis, and medullated nerve fibers had also been reported with this syndrome.2– 6 However, most publications either described VOL. 142, NO. 2
case reports or small series of Apert syndrome or findings of combined craniosynostoses. The aim of this study was to determine the prevalence of ophthalmic findings in Apert syndrome before craniofacial surgery in a large series of patients. Retrospective reviews of 87 patients diagnosed with Apert syndrome from 1975 to 2004 were identified from
BRIEF REPORTS
329
the Australian Craniofacial Unit database. Ethics approval was obtained from institutional review board taking into consideration that informed consent was not possible for patients living overseas. Patients who had craniofacial surgery before their first presentation were excluded. Sixtythree cases (27 males and 36 females) were therefore included in the study. The mean age at first presentation was four years (range 0.1 to 39.2 years, SD 8.21) and the median age was one year. The parameters investigated included visual acuity, cycloplegic refraction, amblyopia, strabismus, anterior segment findings, funduscopic findings, and visual evoked potentials (VEP). Because of the retrospective nature of this study, not all data were present for all parameters: 16 notes contained Snellen visual acuity, 44 had data on cycloplegic refraction, 58 had data on strabismus, 49 had data on amblyopia, 59 had documented anterior segment findings, 60 had documented fundus findings, and 42 had data on VEP. There were at least three patients (5%) with visual impairment worse than 6/12 in the better eye, and at least seven patients (11%) with visual impairment in at least one eye. At least nine patients (14%) had amblyopia. Strabismus was noted in at least 38 patients (60%) of the study population. Exotropia was more common than esotropia (21 patients compared with 11 patients). At least 30 eyes (24%) had hypermetropia ⱖ⫹2 diopters (D), 13 eyes (10%) had myopia ⱕ⫺0.5 diopters, and 37 eyes (29%) had astigmatism ⱖ0.75 diopters. In addition, at least 12 patients (19%) had anisometropia ⱖ0.75 diopters. Fundoscopy revealed optic atrophy in at least five patients (8%), and optic disk edema in three patients (5%). At least nine patients (14%) had abnormal VEP, four bilaterally. Latency was prolonged in six cases while the amplitude was suppressed in three cases. Only two of the nine cases with VEP abnormality had optic atrophy and disk edema. Proptosis was present in at least 55 patients (87%), and corneal scarring and exposure keratopathy were present in at least eight patients (13%). Ptosis (marginal reflex distance ⬍3 mm) was present in at least 14 patients (22%), two were unilateral, and 12 were bilateral (Table). Other notable ophthalmic findings included bilateral myelinated optic nerve fibers (one), entropion (one), epiblepharon (two), trichiasis (two), coloboma of the disk (two), and tortuous retinal vessels (one). This is the largest study reported looking at ophthalmic findings in Apert syndrome before craniofacial intervention. We found that patients with Apert Syndrome were at risk of amblyopia because of high prevalence of refractive errors, anisometropia, and strabismus. Our study is in agreement with earlier studies, which showed that exotropia was more common than esotropia in Apert syndrome.3,4 These patients need regular ophthalmic evaluation for early detection of amblyopia to institute 330
AMERICAN JOURNAL
timely management. Our study also found that exposure keratopathy and corneal scarring occurred commonly. Invariably exposure keratopathy was attributable to inadequate lubrication and lid protection secondary to proptosis.2,3,7 The extent of visual impairment and amblyopia could be better assessed by a prospective study following the cohort through to visual maturation. REFERENCES
1. Cohen MM Jr, Kreiborg S. A clinical study of the craniofacial features in Apert syndrome. Int J Oral Maxillofac Surg 1996;25:45–53. 2. Miller MT. Ocular findings in craniosynostosis. In: Cohen MM Jr, editor. Craniosynostosis, diagnosis, evaluation, and management. 2nd ed. New York: Raven, 1996:184 –194. 3. Buncic JR. Ocular aspects of Apert syndrome. Clin Plast Surg 1991;18:315–319. 4. Hertle RW, Quinn GE, Minguini N, et al. Visual loss in patients with craniofacial synostosis. J Pediatr Ophthalmol Strabismus 1991;28:344 –349. 5. Pollard ZF. Bilateral superior oblique muscle palsy associated with Apert syndrome. Am J Ophthalmol 1988;106:337–340. 6. Margolis S, Pachter BR, Breinin GM. Structural alterations of extraocular muscle associated with Apert syndrome. Br J Ophthalmol 1977;61:683– 689. 7. Ueeck B, Le B, Goodman S, et al. Corneal ulcers in patients with Apert syndrome. J Craniofacial Surg 2001;12:134 –135.
Pigment Release and Secondary Glaucoma After Implantation of Single-piece Acrylic Intraocular Lenses in the Ciliary Sulcus Harvey Siy Uy, MD, and Pik Sha T. Chan, MD PURPOSE: To report the association of sulcus-fixated, single-
piece hydrophobic acrylic intraocular lenses (HAIOL) with pigment release and secondary glaucoma. DESIGN: Interventional case series. METHODS: HAIOL was implanted in the ciliary sulcus of 20 eyes that developed posterior capsule rupture during phacoemulsification. We analyzed postoperative bestcorrected visual acuity, manifest refraction, frequency of intraocular lens malpositioning, and postoperative complications. RESULTS: Postoperative best-corrected visual acuity was 20/40 or better in all eyes. The mean postoperative sphere was ⴚ0.5 ⴞ 0.7 diopters (range ⴙ1.25 to ⴚ2.00); the mean postoperative cylinder was ⴚ1.2 ⴞ Accepted for publication Feb 23, 2006. From the University of the Philippines, Philippine General Hospital (H.S.U.), Manila, and Asian Eye Institute (H.S.U., P.S.T.C.), Makati City, Philippines. Inquiries to Harvey Siy Uy, MD, Asian Eye Institute, 9F Phinma Plaza Building, Rockwell Center, Makati City, Philippines 1200; e-mail: [email protected] OF
OPHTHALMOLOGY
AUGUST 2006