- Email: [email protected]
Congenital iris ectropion uveae presenting with glaucoma in infancy
Congenital iris ectropion uveae presenting with glaucoma in infancy Debbie Laaks, MBChB, DipOphth, and Nicola Freeman, MBChB, FCOphth(SA), MMed(Ophth)
A healthy 5-month-old boy presented with a sporadic unilateral right-sided sectorial ectropion uveae, anterior insertion of the iris root, increased IOP, and glaucomatous disk changes. The absence of other additional ocular anomalies and the appearance of the angle led to a diagnosis of congenital iris ectropion syndrome. IOPs became refractory to maximal topical therapy, and trabeculotomy surgery was performed. The patient has since been stabilized on topical agents.
Case Report
A
5-month-old boy presented to the Department of Ophthalmology, Tygerberg Hospital, University of Stellenbosch, with a chief complaint of persistent rubbing of the right eye, which the parents noted was also visibly larger than the left. The boy was born at term by caesarean delivery, with no fetal or maternal perinatal complications. A thorough systemic examination excluded any neurofibromas, cafe-au-lait spots, blepharoptosis, facial hemihypertrophy, telecanthus, and any syndromic features of Prader-Willi. On ophthalmological examination, he fixated and followed a target but objected to occlusion of the left eye. No nystagmus was noted. The right pupil was round and central, with an apron of ectropion uveae at 12 o’clock. The direct response to light was slightly sluggish, the accommodation response was intact, and there was no relative afferent pupillary defect. The left pupil was 1 mm smaller than the right in both dark and bright illumination and was normal in shape. The left pupil responses were normal (Figure 1A-B). On examination under anesthesia, neither cornea had Haab striae or prominent corneal nerves. The horizontal corneal diameter was 12.5 mm in the right eye and 11 mm in the left eye. The anterior chambers were deep and clear, with no iris nodules or iris transillumination defects. The segment of iris associated with the ectropion had
Author Affiliations: Division of Ophthalmology, Department of Surgical Sciences, Faculty of Health Sciences, University of Stellenbosch, South Africa Presented as a poster at the South African Glaucoma Congress, Cape Town, May 27-29, 2011, and at the World Congress of Paediatric Ophthalmology and Strabismus, Milan, September 8-9, 2012. Submitted July 9, 2012. Revision accepted November 16, 2012. Published online March 25, 2013. Correspondence: Debbie Laaks, MBChB, DipOphth, Division of Ophthalmology, University of Stellenbosch, 7th Floor Tygerberg Hospital, Francie van Zyl Drive, Cape Town, South Africa 7505 (email: [email protected]). J AAPOS 2013;17:214-216. Copyright Ó 2013 by the American Association for Pediatric Ophthalmology and Strabismus. 1091-8531/$36.00 http://dx.doi.org/10.1016/j.jaapos.2012.11.010
214
prominent blood vessels and no iris crypts; however, the remaining iris on the right had crypts that were larger than the iris crypts on the left. There was no heterochromia. The lens had no pigment deposits and the vitreous no strands or degeneration. The right eye had a Spaeth grade B anteriorly inserted iris root on gonioscopy (Figure 2A), an IOP of 25 mm Hg, a cup/disk ratio of 0.7 0.7 with thinning of the neuroretinal rim, and a 2.50 D sphere refractive error. The left eye had a visible trabecular meshwork 360 (Figure 2B), an IOP of 14 mm Hg, a healthy optic nerve, and no refractive error. A small area of flat retinal atrophy at the ora serrata, directly behind the ectropion uveae, was noted (Figure 3). The adjacent 2 ciliary processes were slightly paler but have not changed morphologically over time. The right axial length was 1.4 mm longer on B-scan ultrasonography. The IOPs are the average of results measured with both an Icare (Icare Finland, Helsinki, Finland) and Tono-Pen (Reichert, Buffalo, NY) tonometer under ketamine anaesthesia. Aqueous polymerase chain reaction was negative for all 6 herpes viridae, and no ciliary body mass was detected. Congenital iris ectropion syndrome (CEIS) was diagnosed. Dorzolamide 2% every 8 hours and betaxolol 0.5% every 12 hours was commenced. Average pressures stabilized at 14 mm Hg as measured with the Icare in the clinic. After 6 months, the IOP had increased to 28 mm Hg and an inferotemporal 180 trabeculotomy was performed. Schlemm’s canal was easily identified, and the trabeculotome was passed with little resistance. During the next 3 months, IOPs measured in the clinic were controlled without additional treatment, and the cup/disk ratio remained stable. Three months after surgery, a repeat examination while the patients was under anesthesia revealed an IOP of 32 mm Hg. Dorzolamide 2% every 8 hours and a combination of latanoprost 50 mg/mL and timolol 0.5% once daily were reintroduced. At subsequent examinations the IOP readings ranged from 14 to 18 mm Hg, and to date no further surgery has been necessary.
Discussion CIES consists of iris pigment epithelium on the anterior surface of the iris, hypoplasia of the iris stroma, and angle dysgenesis with anterior insertion of the iris root. The onset of ipsilateral glaucoma usually occurs during childhood or early adolescence. The anomaly is present at birth, and there is no known genetic pattern of inheritance. It has been postulated that there is abnormal neural crest cell migration, but the trigger has not yet been identified. Some authors suggest that a primary vascular insult is the trigger
Journal of AAPOS
Volume 17 Number 2 / April 2013
Laaks and Freeman
215
FIG 1. External photograph of patient at presentation. Note the ectropion with associated loss of iris detail and large iris crypts in the remaining iris of the right eye (A) compared with the normal left eye (B).
FIG 2. Anterior segment Retcam (Clarity Medical Systems, Pleasanton, CA) photograph of the right eye (A) and left eye (B) before surgery. The anterior insertion of the iris root made it difficult to visualize any angle structures. The left eye has an open angle and a visible trabecular meshwork 360 .
FIG 3. Retcam photograph of the right eye showing an atrophic area of retina directly posterior to the ectropion uveae. The area is flat, with no holes, and the ciliary processes are slightly paler.
that arrests neural crest cell development.1 Thus hypoxia could potentially leave a malformed or absent Schlemm’s canal and incomplete cleavage of the iridocorneal angle.
Journal of AAPOS
The area of retinal atrophy and 2 abnormal ciliary processes may support a primary vascular insult as the possible cause. We do not believe that this patient presented with a mild manifestation of combined anterior and posterior persistent fetal vasculature.2 In CIES, there is no hyaloid vessel remnant, Bergmeister’s papillae, Mittendorf’s dot, retrolental fibrovascular membrane, or micophthalmia. The prominent iris vessels are not continuous around the lens to join a vascular complex on the posterior lens capsule, and we thus doubt they are engorged iridohyaloid blood vessels.3 The ciliary body processes are not drawn centrally or elongated, and the atrophic retina does not adhere to any membranes. Ectropion uveae has been described in conditions such as neurofibromatosis, Prader-Willi,4 Axenfeld-Rieger spectrum, and iridocorneal endothelial syndrome. Our patient has no signs suggestive of these conditions but may develop signs of neurofibromatosis later in life. Willcock and colleagues5 described 3 cases of bilateral ectropion uveae, and in 2 a link was found with the PAX6 gene. Bilateral disease should always prompt a thorough investigation into another possible cause. Many of the patients presented in the literature have circumferential ectropion and only progress to glaucoma
216
Laaks and Freeman
in their early teens. Dowling and colleagues6 ascribe the worsening in IOP to a more complete endothelialization of the angle structures. This endothelial lining does not undergo fenestration, and they thus propose that the angle changes very little, but the ectropion may progress. This would explain the presentation of glaucoma later in life. Despite the small apron of ectropion uveae in our patient, the entire angle of the right eye appeared abnormal. Thus, the amount of ectropion does not predict the extent of angle involvement, which is almost always 360 .6 The initial response and control on medication, followed by a rebound increase in IOP that required surgery, is well described in the literature.6 To our knowledge, our patient is the youngest case of CIES to present with glaucoma and the youngest patient requiring surgery. In this case, meticulous examination of the entire eye revealed an unexplained finding of subtle retinal and ciliary body changes adjacent to the ectropion uveae, which may hold clues to the pathophysiology of CIES.
Literature Search A literature search via PubMed and Scopus was performed, without date restrictions, incorporating the following terms: congenital ectropion uveae, glaucoma, and congenital
Volume 17 Number 2 / April 2013 iris ectropion syndrome. The references of relevant articles were reviewed. A formal research on foreign-language databases was not performed; however, if an abstract was available in English it was included. Care was taken to distinguish between true CIES cases and ectropion uveae with other associated ocular or systemic anomalies. References 1. Harasymowycz PJ, Papamatheakis DG, Eagle RC, Wilson RP. Congenital ectropionuveae and glaucoma. Arch Ophthalmol 2006; 124:271-3. 2. M€ ullner-Eidenb€ ock A, Amon M, Moser E, Klebermass N. Persistent fetal vasculature and minimal fetal vascular remnants: A frequent cause of unilateral congenital cataracts. Ophthalmology 2004;111:906-13. 3. Goldberg MF. Persistent fetal vasculature (PFV): An integrated interpretation of signs and symptoms associated with persistent hyperplastic primary vitreous (PHPV). LIV Edward Jackson Memorial Lecture. Am J Ophthalmol 1997;124:587-626. 4. Futterweit W, Ritch R, Teekhasaenee C, Nelson ES. Coexistence of Prader-Willi syndrome, congenital ectropion uveae with glaucoma, and Factor XI deficiency. JAMA 1986;255:3280-82. 5. Willcock C, Grigg J, Wilson M, Tam P, Billson F, Jamieson R. Congenital iris ectropion as an indicator of variant aniridia. Br J Ophthalmol 2006;90:658-9. 6. Dowling JL, Albert DM, Nelson LB, Walton DS. Primary glaucoma associated with iridotrabecular dysgenesis and ectropion uveae. Ophthalmology 1985;92:912-21.
Journal of AAPOS
A healthy 5-month-old boy presented with a sporadic unilateral right-sided sectorial ectropion uveae, anterior insertion of the iris root, increased IOP, and glaucomatous disk changes. The absence of other additional ocular anomalies and the appearance of the angle led to a diagnosis of congenital iris ectropion syndrome. IOPs became refractory to maximal topical therapy, and trabeculotomy surgery was performed. The patient has since been stabilized on topical agents.
Case Report
A
5-month-old boy presented to the Department of Ophthalmology, Tygerberg Hospital, University of Stellenbosch, with a chief complaint of persistent rubbing of the right eye, which the parents noted was also visibly larger than the left. The boy was born at term by caesarean delivery, with no fetal or maternal perinatal complications. A thorough systemic examination excluded any neurofibromas, cafe-au-lait spots, blepharoptosis, facial hemihypertrophy, telecanthus, and any syndromic features of Prader-Willi. On ophthalmological examination, he fixated and followed a target but objected to occlusion of the left eye. No nystagmus was noted. The right pupil was round and central, with an apron of ectropion uveae at 12 o’clock. The direct response to light was slightly sluggish, the accommodation response was intact, and there was no relative afferent pupillary defect. The left pupil was 1 mm smaller than the right in both dark and bright illumination and was normal in shape. The left pupil responses were normal (Figure 1A-B). On examination under anesthesia, neither cornea had Haab striae or prominent corneal nerves. The horizontal corneal diameter was 12.5 mm in the right eye and 11 mm in the left eye. The anterior chambers were deep and clear, with no iris nodules or iris transillumination defects. The segment of iris associated with the ectropion had
Author Affiliations: Division of Ophthalmology, Department of Surgical Sciences, Faculty of Health Sciences, University of Stellenbosch, South Africa Presented as a poster at the South African Glaucoma Congress, Cape Town, May 27-29, 2011, and at the World Congress of Paediatric Ophthalmology and Strabismus, Milan, September 8-9, 2012. Submitted July 9, 2012. Revision accepted November 16, 2012. Published online March 25, 2013. Correspondence: Debbie Laaks, MBChB, DipOphth, Division of Ophthalmology, University of Stellenbosch, 7th Floor Tygerberg Hospital, Francie van Zyl Drive, Cape Town, South Africa 7505 (email: [email protected]). J AAPOS 2013;17:214-216. Copyright Ó 2013 by the American Association for Pediatric Ophthalmology and Strabismus. 1091-8531/$36.00 http://dx.doi.org/10.1016/j.jaapos.2012.11.010
214
prominent blood vessels and no iris crypts; however, the remaining iris on the right had crypts that were larger than the iris crypts on the left. There was no heterochromia. The lens had no pigment deposits and the vitreous no strands or degeneration. The right eye had a Spaeth grade B anteriorly inserted iris root on gonioscopy (Figure 2A), an IOP of 25 mm Hg, a cup/disk ratio of 0.7 0.7 with thinning of the neuroretinal rim, and a 2.50 D sphere refractive error. The left eye had a visible trabecular meshwork 360 (Figure 2B), an IOP of 14 mm Hg, a healthy optic nerve, and no refractive error. A small area of flat retinal atrophy at the ora serrata, directly behind the ectropion uveae, was noted (Figure 3). The adjacent 2 ciliary processes were slightly paler but have not changed morphologically over time. The right axial length was 1.4 mm longer on B-scan ultrasonography. The IOPs are the average of results measured with both an Icare (Icare Finland, Helsinki, Finland) and Tono-Pen (Reichert, Buffalo, NY) tonometer under ketamine anaesthesia. Aqueous polymerase chain reaction was negative for all 6 herpes viridae, and no ciliary body mass was detected. Congenital iris ectropion syndrome (CEIS) was diagnosed. Dorzolamide 2% every 8 hours and betaxolol 0.5% every 12 hours was commenced. Average pressures stabilized at 14 mm Hg as measured with the Icare in the clinic. After 6 months, the IOP had increased to 28 mm Hg and an inferotemporal 180 trabeculotomy was performed. Schlemm’s canal was easily identified, and the trabeculotome was passed with little resistance. During the next 3 months, IOPs measured in the clinic were controlled without additional treatment, and the cup/disk ratio remained stable. Three months after surgery, a repeat examination while the patients was under anesthesia revealed an IOP of 32 mm Hg. Dorzolamide 2% every 8 hours and a combination of latanoprost 50 mg/mL and timolol 0.5% once daily were reintroduced. At subsequent examinations the IOP readings ranged from 14 to 18 mm Hg, and to date no further surgery has been necessary.
Discussion CIES consists of iris pigment epithelium on the anterior surface of the iris, hypoplasia of the iris stroma, and angle dysgenesis with anterior insertion of the iris root. The onset of ipsilateral glaucoma usually occurs during childhood or early adolescence. The anomaly is present at birth, and there is no known genetic pattern of inheritance. It has been postulated that there is abnormal neural crest cell migration, but the trigger has not yet been identified. Some authors suggest that a primary vascular insult is the trigger
Journal of AAPOS
Volume 17 Number 2 / April 2013
Laaks and Freeman
215
FIG 1. External photograph of patient at presentation. Note the ectropion with associated loss of iris detail and large iris crypts in the remaining iris of the right eye (A) compared with the normal left eye (B).
FIG 2. Anterior segment Retcam (Clarity Medical Systems, Pleasanton, CA) photograph of the right eye (A) and left eye (B) before surgery. The anterior insertion of the iris root made it difficult to visualize any angle structures. The left eye has an open angle and a visible trabecular meshwork 360 .
FIG 3. Retcam photograph of the right eye showing an atrophic area of retina directly posterior to the ectropion uveae. The area is flat, with no holes, and the ciliary processes are slightly paler.
that arrests neural crest cell development.1 Thus hypoxia could potentially leave a malformed or absent Schlemm’s canal and incomplete cleavage of the iridocorneal angle.
Journal of AAPOS
The area of retinal atrophy and 2 abnormal ciliary processes may support a primary vascular insult as the possible cause. We do not believe that this patient presented with a mild manifestation of combined anterior and posterior persistent fetal vasculature.2 In CIES, there is no hyaloid vessel remnant, Bergmeister’s papillae, Mittendorf’s dot, retrolental fibrovascular membrane, or micophthalmia. The prominent iris vessels are not continuous around the lens to join a vascular complex on the posterior lens capsule, and we thus doubt they are engorged iridohyaloid blood vessels.3 The ciliary body processes are not drawn centrally or elongated, and the atrophic retina does not adhere to any membranes. Ectropion uveae has been described in conditions such as neurofibromatosis, Prader-Willi,4 Axenfeld-Rieger spectrum, and iridocorneal endothelial syndrome. Our patient has no signs suggestive of these conditions but may develop signs of neurofibromatosis later in life. Willcock and colleagues5 described 3 cases of bilateral ectropion uveae, and in 2 a link was found with the PAX6 gene. Bilateral disease should always prompt a thorough investigation into another possible cause. Many of the patients presented in the literature have circumferential ectropion and only progress to glaucoma
216
Laaks and Freeman
in their early teens. Dowling and colleagues6 ascribe the worsening in IOP to a more complete endothelialization of the angle structures. This endothelial lining does not undergo fenestration, and they thus propose that the angle changes very little, but the ectropion may progress. This would explain the presentation of glaucoma later in life. Despite the small apron of ectropion uveae in our patient, the entire angle of the right eye appeared abnormal. Thus, the amount of ectropion does not predict the extent of angle involvement, which is almost always 360 .6 The initial response and control on medication, followed by a rebound increase in IOP that required surgery, is well described in the literature.6 To our knowledge, our patient is the youngest case of CIES to present with glaucoma and the youngest patient requiring surgery. In this case, meticulous examination of the entire eye revealed an unexplained finding of subtle retinal and ciliary body changes adjacent to the ectropion uveae, which may hold clues to the pathophysiology of CIES.
Literature Search A literature search via PubMed and Scopus was performed, without date restrictions, incorporating the following terms: congenital ectropion uveae, glaucoma, and congenital
Volume 17 Number 2 / April 2013 iris ectropion syndrome. The references of relevant articles were reviewed. A formal research on foreign-language databases was not performed; however, if an abstract was available in English it was included. Care was taken to distinguish between true CIES cases and ectropion uveae with other associated ocular or systemic anomalies. References 1. Harasymowycz PJ, Papamatheakis DG, Eagle RC, Wilson RP. Congenital ectropionuveae and glaucoma. Arch Ophthalmol 2006; 124:271-3. 2. M€ ullner-Eidenb€ ock A, Amon M, Moser E, Klebermass N. Persistent fetal vasculature and minimal fetal vascular remnants: A frequent cause of unilateral congenital cataracts. Ophthalmology 2004;111:906-13. 3. Goldberg MF. Persistent fetal vasculature (PFV): An integrated interpretation of signs and symptoms associated with persistent hyperplastic primary vitreous (PHPV). LIV Edward Jackson Memorial Lecture. Am J Ophthalmol 1997;124:587-626. 4. Futterweit W, Ritch R, Teekhasaenee C, Nelson ES. Coexistence of Prader-Willi syndrome, congenital ectropion uveae with glaucoma, and Factor XI deficiency. JAMA 1986;255:3280-82. 5. Willcock C, Grigg J, Wilson M, Tam P, Billson F, Jamieson R. Congenital iris ectropion as an indicator of variant aniridia. Br J Ophthalmol 2006;90:658-9. 6. Dowling JL, Albert DM, Nelson LB, Walton DS. Primary glaucoma associated with iridotrabecular dysgenesis and ectropion uveae. Ophthalmology 1985;92:912-21.
Journal of AAPOS