Girl has bilaterally increased IOP, abnormal pupils

Examination found posterior embryotoxon and increased cup-to-disc ratio in both eyes.

Mark E. Patron

Andre J. Witkin

A 9-year-old girl presented to the glaucoma service at the New England Eye Center at Tufts Medical Center for evaluation of elevated IOP that had been managed by her pediatric ophthalmologist since age 5 years. Her initial IOPs when evaluated by her pediatric ophthalmologist were 32 mm Hg in the right eye and 27 mm Hg in the left eye. She was placed on dorzolamide and timolol, and her IOP was successfully lowered to 18 mm Hg in both eyes.

The patient’s ocular history was significant for partially accommodative esotropia that was treated successfully with a bilateral medial rectus recession at age 6 years. She was also treated with patching for amblyopia in her left eye. The patient was noted to have maxillary hypoplasia and mild mental retardation. Her medical history also included pulmonic stenosis, a diagnosis made when she was worked up for a heart murmur discovered by her pediatrician during infancy. Of note, her father and sister were also diagnosed with congenital heart defects.

Examination

Visual acuities with mild hyperopic and astigmatism correction were 20/30 in the right eye and 20/30^-2 in the left eye. IOP by applanation measured 17 mm Hg in each eye. Pupil exam revealed bilateral irregular pupils with no afferent pupillary defect (Figures 1a and 1b). The presence of posterior embryotoxon was seen in both eyes (Figure 2). Her posterior exam revealed an increased cup-to-disc ratio in both eyes (Figures 3a and 3b). Gonioscopy was performed and showed iris strands and bands inserting anteriorly into Schwalbe’s line.

Figures 1a and 1b. Marked iris corectopia. Images: Swanic M, Mattox C

Figure 2. Posterior embryotoxon.

Figures 3a and 3b. Increased cup-to-disc ratio in both eyes with inferior notch in the left eye.

What is your diagnosis?

Elevated IOP, posterior embryotoxon

The patient was diagnosed with Axenfeld-Rieger syndrome based on her constellation of eye findings — glaucoma, irregular pupils, posterior embryotoxon and abnormal iris bands — combined with the presence of systemic findings that included mental retardation, maxillary hypoplasia and a congenital heart defect.

Discussion

Axenfeld-Rieger syndrome was originally described more than 100 years ago as a condition that had iris stromal defects combined with various developmental defects. Approximately 50% of these patients develop glaucoma. The inheritance pattern of Axenfeld-Rieger syndrome is autosomal dominant with high penetrance but variable expressivity. Mutations causing similar phenotypic abnormalities have been found on chromosomes 4q25, 6p25 and 13q14.

The abnormalities of Axenfeld-Rieger syndrome appear to present as a continuum of eye and systemic findings. Posterior embryotoxon is a common finding seen in as much as 15% of the normal population and is not associated with glaucoma. Axenfeld’s anomaly refers to posterior embryotoxon combined with iris strands inserting into Schwalbe’s line on gonioscopy; this condition carries an increased risk of glaucoma. Rieger’s anomaly includes all findings in Axenfeld’s anomaly in addition to iris stromal hypoplasia and also incurs an increased risk of glaucoma. Finally, Axenfeld-Rieger syndrome consists of all of these findings with the inclusion of various systemic abnormalities.

Systemic findings in Axenfeld-Rieger syndrome are myriad and highly variable. The presence of these abnormalities should encourage the ophthalmologist to have a patient with classic eye findings undergo further systemic examination, possibly involving a genetics specialist. Commonly described abnormalities include heart valve defects, short stature, maxillary hypoplasia, mental retardation, deafness, dental abnormalities and strabismus.

As the findings can be incredibly varied, many different syndromes have been described in the medical literature that are all likely variants of Axenfeld-Rieger syndrome. In fact, our patient had previously been diagnosed with SHORT syndrome, which encompasses many of the previously discussed abnormalities. Specifically, SHORT syndrome includes short stature, hyperextensible joints, ocular depression, Rieger’s anomaly and teething delay. Clearly, many of these findings overlap with those seen in Axenfeld-Rieger syndrome.

Various researchers have speculated on the pathophysiology of Axenfeld-Rieger syndrome; however, most people consider the most recent theory described by M. Bruce Shields, MD, to be likely responsible for the eye findings. Dr. Shields showed that residual neuroectodermal cells reside on the iris and in the iridocorneal angle. The contraction of these cells may account for the classic gonioscopic findings and distortion of the iris and pupil.

Follow-up

Our patient has been followed by the glaucoma department for nearly 10 years. Over this time period, her IOP, optic nerves and visual fields had been well-controlled on the combination of timolol and dorzolamide. Unfortunately, the patient was lost to follow-up during her late teens, and her parents became poorly compliant with her medical therapy. This resulted in progression of her optic nerve disease and a decline in her visual fields. The patient is now being closely monitored and may undergo surgical management with trabeculectomy if her disease continues to progress.

References:

• Alward WL. Axenfeld-Rieger syndrome in the age of molecular genetics. Am J Ophthalmol. 2000;130(1):107-115.
• Krachmer JH, Mannis MJ, Holland EJ. Cornea: Fundamentals, Diagnosis and Management. Mosby; 2005.
• Shields MB. Axenfeld-Rieger syndrome: a theory of mechanism and distinctions from the iridocorneal endothelial syndrome. Trans Am Ophthalmol Soc. 1983;81:736-784.

• Matthew Swanic, MD, and Cynthia Mattox, MD, can be reached at New England Eye Center, Tufts University School of Medicine, 750 Washington St., Box 450, Boston, MA 02111; 617-636-4219; fax: 617-636-4866; website: www.neec.com.

• Edited by Mark E. Patron, MD, and Andre J. Witkin, MD. Drs. Patron and Witkin can be reached at New England Eye Center, Tufts University School of Medicine, 750 Washington St., Box 450, Boston, MA 02111; 617-636-4219; fax: 617-636-4866; website: www.neec.com.