Journal of Pediatric Ophthalmology and Strabismus

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Short Subjects 

Bilateral Massive Posterior Embryotoxon

Joshua S. Manusow, MD; Seymour Brownstein, MD, FRCSC; Michel J. Belliveau, MD

Abstract

A 10-week-old infant died suddenly and unexpectedly. Histopathologic examination of the globes showed no signs of trauma but did disclose incidental bilateral, extremely prominent Schwalbe’s rings (posterior embryotoxon). The authors believe this case is the largest example of posterior embryotoxon ever published and present a brief review of its associated syndromes.

Abstract

A 10-week-old infant died suddenly and unexpectedly. Histopathologic examination of the globes showed no signs of trauma but did disclose incidental bilateral, extremely prominent Schwalbe’s rings (posterior embryotoxon). The authors believe this case is the largest example of posterior embryotoxon ever published and present a brief review of its associated syndromes.

From the Departments of Ophthalmology and Laboratory Medicine (Pathology), University of Ottawa; and The Ottawa Hospital, Ottawa, Ontario, Canada.

The authors have no financial or proprietary interest in the materials presented herein.

Address correspondence to Seymour Brownstein, MD, FRCSC, University of Ottawa Eye Institute, 501 Smyth Road, Suite W6213, Ottawa, Ontario K1H 8L6, Canada. E-mail: sbrownstein@ohri.ca

Received: March 24, 2010
Accepted: June 15, 2010
Posted Online: September 22, 2010

Introduction

Posterior embryotoxin is an ocular finding that is common in healthy individuals, but also is associated with several diseases. We describe a case of bilateral massive posterior embryotoxin and review the literature to elucidate both the benign nature of and the more serious syndromes associated with this lesion.

Case Report

A 10-week-old infant died suddenly and unexpectedly. Both eyes were obtained at autopsy. Post-mortem gross examination of the globes was unremarkable and disclosed a right cornea measuring 9.5 × 9 mm and a left cornea measuring 10 × 9.5 mm. Histopathologic examination was consistent with the patient’s age and showed prominent Lange’s folds but did not show any evidence of trauma, cataracts, synechiae, or secondary glaucoma. However, it did disclose incidental bilateral, large, extremely prominent, moderately cellular posterior embryotoxon measuring 560 × 160 μm in the right eye and 290 × 90 μm in the left eye (Figure). The underlying cause of death was sudden infant death syndrome.

Bilateral Prominent Schwalbe’s Rings (posterior Embryotoxon) Are Shown (arrows). Note that the Posterior Embryotoxon in the Right Eye (OD) Is Significantly Larger, Measuring 590 × 160 μm, than in the Left Eye (OS), Which Measures 290 × 90 μm (hematoxylin–Eosin, Original Magnification ×250 [right Eye] and ×125 [left Eye]).

Figure. Bilateral Prominent Schwalbe’s Rings (posterior Embryotoxon) Are Shown (arrows). Note that the Posterior Embryotoxon in the Right Eye (OD) Is Significantly Larger, Measuring 590 × 160 μm, than in the Left Eye (OS), Which Measures 290 × 90 μm (hematoxylin–Eosin, Original Magnification ×250 [right Eye] and ×125 [left Eye]).

Discussion

Posterior embryotoxon is a prominent, anteriorly displaced Schwalbe’s line, the junction of Descemet’s membrane and the trabecular meshwork, which appears clinically as a white line on the posterior cornea near the limbus.1–3 Although it is a component of the Axenfeld–Reiger spectrum of disorders, as an isolated ocular finding posterior embryotoxon has no known pathologic significance.3 Classically, it has been reported to be present in anywhere from 8% to 32% of the population; however, a recent prospective study found an incidence of 6.8% in a general ophthalmology clinic.2

Because posterior embryotoxon is not a pathologic finding in and of itself, little has been published on the subject in the modern era. We performed a literature search and could find few examples of posterior embryotoxon that were quantified by size. Furthermore, we could not find any published images of prominent Schwalbe’s rings that are comparable in size to ours. We believe that the largest posterior embryotoxon published until now was in Sir Stewart Duke-Elder’s System of Ophthalmology.4 However, using their scale bar we calculated the dimensions of this early example to be approximately 200 × 50 μm. Our case is almost three times this size in the right eye and 1½ times larger in the left eye. Our case thus appears to demonstrate the largest example of posterior embryotoxon ever published.

The specimens for our case were submitted to rule out trauma as the cause of this unfortunate death. Thorough histopathological examination did not show signs of trauma such as retinal or subdural hemorrhages, but did show bilateral posterior embryotoxon. Because posterior embryotoxon can be associated with systemic syndromes, it is possible that this infant’s death was due to a lethal manifestation of a related systemic disease.

It is important to differentiate posterior embryotoxon from Axenfeld–Reiger syndrome (Table) because the former is not associated with glaucoma.3 Axenfeld–Reiger syndrome is a spectrum and encompasses a wide range of phenotypes with minor differences. In general, these include ocular findings such as posterior embryotoxon, anomalous development of the limbus, anterior chamber angle and iris, and systemic features including facial, dental, and osseous abnormalities.5

Conditions Featuring Posterior Embryotoxon

Table: Conditions Featuring Posterior Embryotoxon

Posterior embryotoxon is an ocular finding in Alagille syndrome6 (Table) and identification of it by the ophthalmologist in a neonate with cholestasis can lead to early diagnosis. This potentially lethal syndrome is inherited as an autosomal dominant trait with low penetrance and highly variable expressivity that results from mutations in the Jagged1 gene on chromosome 20p12. Its main feature is cholestasis, but also includes cholestatic facies; vertebral, cardiac, vascular, and renal abnormalities; mental retardation; and endocrinopathies. Unlike Axenfeld–Reiger syndrome, Alagille syndrome is associated with an isolated posterior embryotoxon with no associated iris processes or glaucoma and a good visual acuity.6 Additional related ocular findings include small corneal diameters, iris stromal hypoplasia, elevated optic discs, tortuous, angulated vessels or vessels with abnormal branching patterns, and pigmentary retinopathy.6 The vascular abnormalities are particularly important because they are a clue that other vasculature, such as the pulmonary arteries, intracranial vessels, aorta, and renal, celiac, superior mesenteric, and subclavian arteries may be affected.6 These anomalies can lead to pulmonary tree stenosis, aortic aneurysms, renal artery stenosis, intracranial hemorrhage, and stroke and can be fatal.7 Thus, recognition of posterior embryotoxon with associated retinal abnormalities can lead to early diagnosis and possible reduction in morbidity and mortality.6

The 22q11.2 deletion syndrome (Table) includes Digeorge syndrome, velocardiofacial (Shprintzen) syndrome, conotruncal-anomaly-face (Takao) syndrome, Optiz G/BBB syndrome, and Cayler cardiofacial syndrome.8 In a study of 90 patients with 22q11.2 deletions confirmed by fluorescent in situ hybridization, 44 patients (49%) had a posterior embryotoxon and this was the most frequently observed ocular sign.8

Posterior embryotoxon may be associated with X-linked ocular albinism (Table). Eighteen families of affected males were studied and 30% of the affected men had a posterior embryotoxon.9 Posterior embryotoxon was seen more frequently in the affected men than women carriers or normal individuals within the families and this finding was statistically significant.9

Hermansky–Pudlak syndrome (Table) is an autosomal recessively inherited disorder of tyrosine-positive oculocutaneous albinism, bleeding diathesis, and ceroid accumulation in tissues. In a study of 55 patients with this rare disorder, 27% had posterior embryotoxon.10

We believe that our case of bilateral prominent posterior embryotoxon is the largest such lesion ever published. Although posterior embryotoxon is not a rare finding in the general population, it is frequently overlooked. The cause of death in our case was presumably sudden infant death syndrome and not one of the aforementioned syndromes, but the presence of posterior embryotoxon in association with other ocular and systemic features can be indicative of a more damaging or even lethal genetic disease, and it is important for the ophthalmologist to recognize and document its existence. In addition to the previously mentioned syndromes, several published cases of posterior embryotoxon in isolated patients with other rare diseases further highlight the fact that its presence may be indicative of other serious underlying conditions. Therefore, as with many other ocular signs of systemic illness, the ophthalmologist has the opportunity to play a key role in early diagnosis by recognizing this readily identifiable finding during a careful external ocular examination.

References

  1. Hjalt TA, Semina EV. Current molecular understanding of Axenfeld-Reiger syndrome. Expert Rev Mol Med. 2005;7:1–17. doi:10.1017/S1462399405010082 [CrossRef]
  2. Rennie CA, Chowdhury S, Khan J, et al. The prevalence and associated features of posterior embryotoxon in the general ophthalmic clinic. Eye. 2005;19:396–399. doi:10.1038/sj.eye.6701508 [CrossRef]
  3. Shields MB, Buckley E, Klintworth GK, Thresher R. Axenfeld-Rieger syndrome: a spectrum of developmental disorders. Surv Ophthalmol. 1985;29:387–409. doi:10.1016/0039-6257(85)90205-X [CrossRef]
  4. Burian HM, Braley A, Allen L. Schwalbe’s Ring-Fig 554. In: Duke-Elder S, ed. System of Ophthalmology, vol. 3. St. Louis: Mosby; 1964:519.
  5. Yanoff M, Sassani JW. Cornea and sclera: congenital defects. In: Yanoff M, Sassani JW, eds. Ocular Pathology, vol. 3, 6th ed. St. Louis: Mosby; 2009:263–264.
  6. Kim BJ, Fulton AB. The genetics and ocular findings of Alagille syndrome. Semin Ophthalmol. 2007;22:205–210. doi:10.1080/08820530701745108 [CrossRef]
  7. Kamath BM, Spinner NB, Emerick KM, et al. Vascular anomalies in Alagille syndrome: a significant cause of morbidity and mortality. Circulation. 2004;109:1354–1358. doi:10.1161/01.CIR.0000121361.01862.A4 [CrossRef]
  8. Forbes BJ, Binenbaum G, Edmond JC, et al. Ocular findings in the chromosome 22q11.2 deletion syndrome. J AAPOS. 2007;11:179–182. doi:10.1016/j.jaapos.2006.08.006 [CrossRef]
  9. Charles SJ, Green JS, Grant JW, Yates JR, Moore AT. Clinical features of affected males with X- linked ocular albinism. Br J Ophthalmol. 1993;77:222–227. doi:10.1136/bjo.77.4.222 [CrossRef]
  10. Izquierdo NJ, Townsend W, Hussels IE. Ocular findings in the Hermansky-Pudlak syndrome. Trans Am Ophthalmol Soc. 1995;93:191–200.

Conditions Featuring Posterior Embryotoxon

ConditionAssociation
Axenfeld–Reiger syndrome1,3Strong
Alagille syndrome6,7Strong
22q11.2 deletion syndrome8Moderate
X-linked ocular albinism9Weak
Hermansky–Pudlak syndrome10Weak
Authors

From the Departments of Ophthalmology and Laboratory Medicine (Pathology), University of Ottawa; and The Ottawa Hospital, Ottawa, Ontario, Canada.

The authors have no financial or proprietary interest in the materials presented herein.

Address correspondence to Seymour Brownstein, MD, FRCSC, University of Ottawa Eye Institute, 501 Smyth Road, Suite W6213, Ottawa, Ontario K1H 8L6, Canada. E-mail: sbrownstein@ohri.ca

10.3928/01913913-20100920-07

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