Ocular Biomarkers differentiating Axenfled-Reiger Syndrome from other anterior segment dysgenesis

Debasish Dhar, Bachelor’s in clinical Optometry

Fellow Optom, Dr. Shroff Charity Eye Hospital, New Delhi, India

 

Background

Anterior Segment Dysgenesis (ASD) is a developmental abnormality of the tissues of the anterior segment of the eye. ⁽¹⁾ ASDs include combinations of congenital abnormalities affecting the iris and cornea which leads to risk of glaucoma and corneal opacity. ⁽¹⁾ Axenfled- Reiger Syndrome (ARS) is one such example which is due to developmental anomalies of the anterior chamber structures. Axenfeld–Rieger syndrome is a rare autosomal dominant disorder, involving both ocular and extraocular structures. ^{(2) (3)} ARS covers a spectrum of inherited disorders and traditionally was classified into 3 subcategories. Axenfeld’s anomaly ⁽²⁾ (limited to peripheral anterior segment defects); Rieger’s anomaly ⁽²⁾ (peripheral abnormalities with additional changes in the iris); and Rieger’s syndrome ⁽²⁾ (ocular anomalies plus non ocular developmental defects). Thus, the term ARS has been used since 1985, ⁽⁴⁾ and Ozeki et al ⁽⁵⁾ reported that Axenfeld anomaly accounted for 71%, Rieger anomaly accounted for 10%, while Reiger syndrome covered 19% of all ARS cases.

Clinical Ocular Signs:

The Schwalbe’s line is prominent and displaced anteriorly i.e., posterior embryotoxon (Figure 1). Iris hypolasis, corectopia and polycoria (Figure 2) are the typical characteristics of ARS. ⁽⁶⁾ The iris strands may be attached to the Schwalbe’s line (Figure 3) and may have variable thickness.

Figure 1: Posterior embryotoxon, diffuse iris atrophy and corectopia

[Pic courtesy : https://www.google.com/webeye.ophth.uiowa.edu/eyeforum/Atlass/pages/Axenfeld-Rieger/index.htm]

 

Figure 2: Posterior embryotoxon, corectopia and polycoria

[Pic courtesy: https://www.semanticscholar.org.Brief-report%253A-Axenfeld-Rieger-Syndrome-Associated-Subdural-Hematoma/index.com]

 

Figure 3: Gonioscopy picture of iris strands attached to Schwable’s line

[Pic courtesy: https://www.researchgate.net/figure/Two-gonioscopic-photographs-demonstrating-posterior-embryotoxon-and-iridocorneal_fig1_51893925]

 

Systemic Characteristic:

Hypertelorism, telecanthus (Figure 4), maxillary hypoplasia, microdontia (Figure 5) and fewer teeth than normal are observed in ARS⁽⁶⁾. Redundant periumbilical skin (Figure 6) can be seen which is often mistaken as umbical hernia ^(7,8).

Figure 4: Hypertelorism and telecantus in ARS

[Pic courtesy: https://webeye.ophth.uiowa.edu/eyeforum/cases/174-Axenfeld-Rieger-Cataract.htm]

 

Figure 5: Microdentia and diastema in ARS ^(e)

[Pic courtesy: https://disorders.eyes.arizona.edu/disorders/axenfeld-rieger-syndrome-type-1 ]

 

Figure 6: Incomplete involution of umbilicus in ARS

[Pic courtesy: https://disorders.eyes.arizona.edu/disorders/axenfeld-rieger-syndrome-type-1/]

 

Embryology of the anterior chamber:

During embryogenesis neural crest cells differentiate to form structures of the anterior segment of the eye. ⁽⁹⁾ Developmental arrest that occurs late in gestation results in the neural crest cells being retained over parts of the iris and anterior chamber angle, thus affecting its anatomy. ⁽⁹⁾ In addition, contraction of the primordial layer causes iris stromal thinning, corectopia and hole formation, all of which are malformations observed in ARS. ^{(6, 9)}

Genetic basis of ARS:

It has been widely accepted that mutations in genes FOXC1 (chromosomes 6p25) and PITX2 (chromosomes 4q25) may lead to ARS. ⁽¹⁰⁾ Another locus chromosome 13q14 was also related to ARS but its function has not been identified yet. ⁽¹¹⁾

Ocular management and treatment:

• Refractive error should be corrected.
• Cosmetics coloured contact lenses for cosmetic purpose and tinted glasses for glare issue can be suggested.
• Anti-glaucoma medication and glaucoma surgery can be planned in managing glaucoma.

 

Differentiating ARS from ICE syndrome and Peter’s anomaly

Figure 7: ICE Syndrome having corneal edema, iris atrophy and anterior synechiae

[Pic courtesy: https://www.researchgate.net/figure/A-patient-with-Chandler-syndrome-and-glaucoma-in-her-right-eye-showing-moderate-corneal_fig2_283104886]

 

Figure 8: Peter’s anomaly having central corneal opacity and posterior synechiae

[Pic courtesy: https://www.opticianonline.net/cet-archive/4886]

 

Figure 9: ARS having corectopia, polycoria, iris hypoplasia and posterior embryotoxon

[Pic courtesy : https://www.google.com/webeye.ophth.uiowa.edu/eyeforum/Atlass/pages/Axenfeld-Rieger/index.htm]

The Irido-corneal Endothelium (ICE) syndrome Peter’s anomaly may be confused with the ARS based on certain clinical and histopathology similarities. However, the two entities are distinctly separate from ARS. ICE syndrome is believed to be an abnormality of the corneal endothelium which frequently leads to corneal edema with a secondary proliferation of a tissue layer over the anterior chamber angle and iris (Figure 7). ⁽²⁾ Peters’ anomaly (PA) is a congenital ocular anomaly characterized by central corneal opacities, iridocorneal adhesions (iris lens and/or lens cornea) due to malformations of the posterior corneal stroma and absence of Descemet’s membrane and the corneal endothelium (Figure 8). ⁽¹²⁾ While ARS is thought to represent a developmental arrest with retention of a primordial membrane and other developmental defects characterized by posterior embryotoxon and iris stromal hypoplasia ⁽³⁾ (Figure 9).

 

Reference:

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