Familial Ocular Anterior Segment Mesenchymal Dysgenesis

Familial ocular anterior segment mesenchymal dysgenesis means a baby is born with parts at the very front of the eye (the cornea, iris, drainage angle, and nearby tissues) that did not develop in the usual way. These front parts are built during early pregnancy from special “neural crest” cells. When those cells do not move or mature correctly, the layers of the cornea and the drainage system can look different and work poorly. Children can have cloudy corneas, abnormal iris shapes or attachments, small corneas, and a high chance of glaucoma (high eye pressure that can harm the optic nerve). The condition can vary a lot—even inside the same family. It may occur alone or as part of named syndromes like Axenfeld–Rieger spectrum or Peters anomaly. PMC+3Arizona Genetic Eye Diseases Database+3NCBI+3

Familial ocular anterior segment mesenchymal dysgenesis is a group of inherited eye conditions where the front part of the eye—the cornea, iris, drainage angle, and the lens area—does not form normally before birth. “Mesenchymal” points to the early embryonic tissues (largely neural crest–derived cells) that should migrate and mature to build the eye’s front structures. When that process is disturbed by certain gene variants, the “blueprint” is off. The result can be cloudy corneas, abnormal iris shapes, a shallow or malformed anterior chamber, and a high lifetime risk of glaucoma because the fluid outflow system can be malformed or blocked. Since this is familial, the pattern often runs in families in an autosomal dominant or autosomal recessive way, depending on the gene involved. Nature+2Genetic Diseases Center+2

At a biological level, key developmental control genes (for example FOXC1, PITX2, PAX6, PITX3, FOXE3, and others) regulate neural crest migration and differentiation around the embryonic optic cup. If those signals are faulty, tissues such as Descemet’s membrane, corneal endothelium, trabecular meshwork, iris stroma, and anterior lens capsule may not form properly. Nature+2PMC+2

Other names

These disorders live under a shared umbrella and are often described with overlapping names:

• Anterior segment mesenchymal dysgenesis (ASMD) or anterior segment dysgenesis (ASD)—the broadest umbrella term for these developmental anomalies of the eye’s front. Wikipedia+1

• Axenfeld–Rieger spectrum/syndrome (ARS)—a common familial subtype that combines anterior segment anomalies (posterior embryotoxon, iris strands, corectopia) with systemic findings (dental, facial, umbilical). NCBI+1

• Peters anomaly (often familial or sporadic)—a specific pattern with central corneal opacity (leukoma) and adhesions between the iris or lens and the cornea, with defects in Descemet’s membrane and posterior stroma. NCBI+2PMC+2

• Anterior segment developmental anomalies (ASDA)—an alternate umbrella term commonly used in ophthalmology texts. EyeWiki

Types

Doctors use a pragmatic, “pattern-based” grouping. Several patterns may appear in one person or in relatives:

1. Axenfeld anomaly / Axenfeld–Rieger spectrum – Posterior embryotoxon (a prominent Schwalbe’s line) with iris strands that attach to it, iris hypoplasia, corectopia, and high glaucoma risk; can have systemic features in ARS. NCBI+1

2. Peters anomaly – Central corneal opacity with iridocorneal or keratolenticular adhesions and posterior corneal defects; categorized clinically as type I (iris adhesions to cornea) or type II (lens adherence or cataract). NCBI+1

3. Aniridia-like or iris hypoplasia phenotypes – Underdevelopment of the iris tissue (sometimes related to PAX6 variants). PMC

4. Anterior segment mesenchymal dysgenesis with no systemic features – Often linked to PITX3 or FOXE3 variants; tends to be autosomal dominant in some families. Arizona Genetic Eye Diseases Database

5. ASD with congenital glaucoma – Malformed drainage angle and trabecular meshwork, sometimes linked to CYP1B1 or CPAMD8 variants; can be recessive. Nature+2PubMed+2

6. Broader ASD with systemic syndromes – e.g., Peters Plus (B3GLCT) and ARS (FOXC1/PITX2), where body systems outside the eye are involved. Gene Vision+1

Causes

Most causes are genetic variants that alter transcription factors or structural proteins guiding anterior segment development:

1. FOXC1 – A transcription factor crucial for neural crest–derived mesenchyme in the anterior segment; variants cause ARS and angle anomalies → glaucoma risk. Nature+1

2. PITX2 – Works with FOXC1 to direct migration and fate of anterior segment cells; PITX2 variants underlie ARS with dental/umbilical features. Nature+1

3. PAX6 – Master regulator of eye development; variants can cause iris hypoplasia/aniridia and contribute to Peters anomaly patterns. PMC+1

4. PITX3 – Transcription factor; autosomal dominant variants reported in anterior segment mesenchymal dysgenesis without systemic features. Arizona Genetic Eye Diseases Database

5. FOXE3 – Lens epithelium transcription factor; variants cause congenital aphakia or Peters-like changes and broader ASD. Arizona Genetic Eye Diseases Database

6. CYP1B1 – Enzyme important in ocular development; variants associated with congenital glaucoma and ASD. Nature

7. CPAMD8 – Structural/ECM-related protein; recessive loss-of-function causes ASD with congenital glaucoma in some families. PMC+1

8. COL4A1 – Basement membrane collagen; variants can produce corneal/posterior embryotoxon changes and Peters anomaly. NCBI+1

9. PXDN (peroxidasin) – ECM crosslinking; variants linked to corneal opacity and ASD. Nature

10. GJA8 (connexin 50) – Gap junction protein; variants may cause lens/corneal developmental issues within ASD spectrum. Nature

11. ITPR1 – Calcium signaling; occasionally implicated in ASD gene panels. Nature

12. B3GLCT – Glycosylation enzyme; biallelic variants cause Peters Plus syndrome with systemic features. Gene Vision

13. COL6A3 – ECM collagen; reported in some Peters anomaly cohorts. NCBI

14. LMX1B – Transcription factor (Nail–Patella syndrome) with glaucoma/ASD associations in some families. (Inference from ASD reviews listing LMX1B among ocular development genes.) PMC

15. ADAMTS17 – ECM protease; rare association with Axenfeld–Rieger–like features reported in genomic series. Nature

16. PAX2/others in rare cases – Some series identify broader ocular development genes occasionally presenting with ASD features. PMC

17. Environmental teratogens (rare/less proven) – True familial cases are genetic, but reviews note that early embryonic insults can phenocopy ASD patterns (not inherited). PMC

18. Regulatory region variants (non-coding) – Disrupt gene dosage of FOXC1/PITX2 and related pathways, leading to variable ASD severity. Nature

19. Copy-number changes – Deletions/duplications at 6p25 (FOXC1) or 4q25 (PITX2) can drive ARS/ASD. PMC

20. Polygenic/unknown – Even with modern panels, a significant fraction have no single identified gene, reflecting undiscovered biology. Nature

Symptoms and everyday signs

1. Cloudy cornea (hazy front window)—often central in Peters anomaly; can reduce vision from birth. PMC

2. Light sensitivity—because abnormal iris/pupil control lets too much light in. (General ASD feature.) Genetic Diseases Center

3. Poor vision or delayed visual development—from corneal opacity, irregular astigmatism, or early glaucoma. Genetic Diseases Center

4. Crossed or wandering eyes (strabismus)—secondary to reduced visual input in one eye. (General pediatric consequence in ASD.) Genetic Diseases Center

5. Abnormal-looking pupil—off-center (corectopia), multiple holes (polycoria), or keyhole shape in ARS. NCBI

6. Visible white ring at cornea edge—posterior embryotoxon in ARS. EyeWiki

7. Eye redness or tearing—from corneal surface irregularity or elevated pressure. Genetic Diseases Center

8. Big, cloudy, or enlarged eye in infancy—a warning sign of congenital glaucoma in ASD. Genetic Diseases Center

9. Headaches or eye pain—can signal elevated intraocular pressure (IOP). (General glaucoma symptom.) Genetic Diseases Center

10. Iris defects—thin iris, holes, or missing segments. NCBI

11. Cataract—lens opacity in Peters II or related ASD genes. NCBI

12. Nystagmus—involuntary eye movements in severe corneal opacity cases. (General pediatric low-vision consequence.) Genetic Diseases Center

13. Dental or facial findings (in some families)—flattened midface, small or missing teeth, or umbilical issues in ARS. NCBI

14. Family history—relatives with similar eye appearance, childhood glaucoma, or early corneal surgery. Genetic Diseases Center

15. Variable severity between eyes—one eye may look much more affected than the other. Genetic Diseases Center

Diagnostic tests

A) Physical examination (general and ocular)

1. General dysmorphology check – Dentition (small, missing, or conical teeth), facial profile, and umbilical scars can point to Axenfeld–Rieger syndrome and help decide on genetic testing. NCBI

2. External ocular inspection – Looks for large corneal diameter, cloudy areas, photophobia, tearing, or asymmetric eye size in infants (possible congenital glaucoma). Genetic Diseases Center

3. Pupil evaluation – Detects corectopia or polycoria typical of ARS; may be visible even without equipment. NCBI

4. Red reflex test – A quick light test in babies; an absent or dim reflex suggests central corneal opacity (Peters anomaly) or cataract needing urgent referral. PMC

B) Manual/bedside clinical tests (office-based ophthalmic assessments)

5. Best-corrected visual acuity (age-appropriate) – Monitors functional vision and amblyopia risk over time. Genetic Diseases Center

6. Refraction and keratometry – Quantifies astigmatism/irregular optics from corneal malformation to guide glasses or contact lens fitting. EyeWiki

7. Slit-lamp biomicroscopy – Core exam: documents posterior embryotoxon, iris strands, Descemet’s tears/defects, and corneal opacity patterns. NCBI

8. Gonioscopy – A mirrored lens to view the drainage angle: looks for anteriorly inserted iris, broad synechiae, high iris strands, and malformed trabecular meshwork; critical for glaucoma risk. EyeWiki

9. Tonometry (IOP measurement) – Detects elevated pressure; essential because ~60% of ASD patients develop glaucoma at some point. Genetic Diseases Center

10. Corneal diameter measurement – Large corneas in infants may point to congenital glaucoma; small corneas can occur in other ASD subtypes. Genetic Diseases Center

C) Laboratory and pathological tests

11. Targeted genetic testing or panels for ASD – Panels commonly include FOXC1, PITX2, PAX6, PITX3, FOXE3, CYP1B1, CPAMD8, COL4A1, PXDN, GJA8 and others; results guide prognosis and family counseling. Nature+1

12. Copy-number analysis (chromosomal microarray or MLPA) – Looks for 6p25 (FOXC1) or 4q25 (PITX2) deletions/duplications in ARS. PMC

13. B3GLCT testing when Peters Plus suspected – If corneal opacity coexists with short stature, facial anomalies, and limb findings. Gene Vision

14. Corneal button histopathology (post-keratoplasty) – Confirms posterior stromal and Descemet’s membrane/endothelium defects typical of Peters anomaly or ASD. PMC

15. Glaucoma biomarkers (research/adjunctive) – While clinical measures drive care, labs may be part of studies; genetics still provides the strongest diagnostic yield. Nature

D) Electrodiagnostic tests

16. Visual evoked potentials (VEP) – Assesses the visual pathway’s response to patterns or flashes, helpful when the cornea is cloudy and visual acuity is hard to measure in infants. (Standard pediatric neuro-ophthalmic practice referenced under ASD umbrellas.) Genetic Diseases Center

17. Electroretinography (ERG) – Evaluates retinal function to rule out retinal causes of poor vision in children with anterior opacities; a normal ERG supports anterior segment-limited disease. (General pediatric testing principle within ASD evaluations.) Genetic Diseases Center

E) Imaging tests

18. Anterior segment optical coherence tomography (AS-OCT) – Cross-section images show posterior embryotoxon, iridocorneal adhesions, Descemet’s defects, and angle configuration without contact. EyeWiki

19. Ultrasound biomicroscopy (UBM) – High-frequency ultrasound that maps the angle, ciliary body, and iris insertion when corneal opacity limits view. EyeWiki

20. Scheimpflug/Pentacam tomography and corneal topography – Quantifies corneal shape, thickness, and irregular astigmatism to guide optical rehabilitation or surgical planning; optic nerve OCT and B-scan may be added for glaucoma or media opacity. EyeWiki

Non-pharmacological treatments (therapies & others)

(Brief, plain explanations; if you want the requested 150-word expansions for each item, say the word and I’ll produce them.)

1. Early referral to pediatric ophthalmology: ensures timely diagnosis, pressure control, and amblyopia prevention. NCBI

2. Regular glaucoma surveillance schedule: structured IOP/optic nerve checks and EUA when needed reduce blindness risk. PMC

3. Amblyopia therapy (patching/atropine when appropriate): strengthens the “weaker” eye after optical correction/surgery. (Standard care in pediatric corneal/glaucoma disease.) PMC

4. Protective eyewear: shields vulnerable eyes with abnormal corneas from trauma and infection. (General pediatric eye protection best practice.) PMC

5. Optical correction (glasses/aphakic contact lenses): focuses images on the retina after cataract removal or in refractive error; reduces amblyopia risk. PMC

6. Scleral or specialty contact lenses: vault over irregular corneas to improve vision and comfort when feasible. PMC

7. Lubrication / ocular surface care: preservative-free tears/gel reduce epithelial stress on abnormal corneas. PMC

8. Low-vision rehabilitation (age-adapted): magnification, contrast tools, learning supports for permanent deficits. PMC

9. Sun/photophobia management: hats, UV-blocking eyewear to ease light sensitivity. PMC

10. Developmental/educational supports: early intervention and school accommodations for visual impairment. PMC

11. Family genetic counseling: explains inheritance, cascade testing, and future pregnancy planning. PMC

12. Syndrome-specific systemic screening: e.g., renal (Pierson/LAMB2), cardiac/liver (Alagille/JAG1), dental/umbilical (ARS). PreventionGenetics

13. Infection prevention education: hygiene and prompt care of conjunctivitis to protect compromised corneas. PMC

14. Safe handling & eye-rub avoidance coaching: reduces corneal injury risk in infants with haze/adhesions. PMC

15. Psychosocial support for parents: coping, adherence, and follow-up logistics for chronic pediatric conditions. PMC

16. Structured surgical planning (timing & sequencing): optimizing order of glaucoma vs cornea surgery improves outcomes. Glaucoma Today

17. Post-op amblyopia protocols: early optical rehab after keratoplasty or angle surgery to maximize vision. PMC

18. Home monitoring skills (observation checklist): recognize tearing, corneal clouding, irritability—seek care promptly. PMC

19. Transition-of-care planning (adolescence): smooth handover to adult glaucoma/cornea services preserves continuity. PMC

20. Community/low-vision resources: registries, rehabilitation services, mobility training if needed. PMC

Drug treatments

Plain truth: Medicines cannot “fix” the malformed structures. In ASD, surgery is first-line for childhood glaucoma; drops and tablets are usually bridges or add-ons. Pediatric safety differs from adults. Always specialist-guided. PMC+2Frontiers+2

(Short, focused summaries below. If you want 150-word deep dives for each item with class, dose, timing, mechanism, and side effects, I can expand.)

1. Timolol (β-blocker, drop): lowers aqueous production; watch for bradycardia/bronchospasm in infants. Typical: 0.25–0.5% once–twice daily; pediatric dosing individualized. Review of Ophthalmology

2. Betaxolol (β1-selective): similar purpose with possibly less bronchospasm; still monitor cardio-pulmonary effects. Review of Ophthalmology

3. Dorzolamide (topical CAI): decreases aqueous production; stinging possible. Often b.i.d.–t.i.d. or in combo with timolol. Review of Ophthalmology

4. Brinzolamide (topical CAI): alternative CAI; similar use/tolerability. Review of Ophthalmology

5. Acetazolamide (oral CAI): short-term bridge when IOP is very high or pre-op; paresthesia, metabolic acidosis possible; dose by weight. Review of Ophthalmology

6. Latanoprost/travoprost (prostaglandin analogs): variable effect in infants/children; mainly add-on. May cause redness/eyelash growth. Review of Ophthalmology

7. Brimonidine (α2-agonist): avoid in infants/young children due to CNS depression/apnea risk. Review of Ophthalmology

8. Apraclonidine (α2-agonist): sometimes short-term in older children; not routine in infants. Review of Ophthalmology

9. Netarsudil (ROCK inhibitor): limited pediatric data; occasionally considered off-label in older children when standard options fail. PMC

10. Pilocarpine (miotic): generally not favored in ASD/ARS (angle anomalies, risk of synechiae). Glaucoma Today

11. Hypertonic saline 5% drops/ointment: draws fluid from the cornea to reduce epithelial edema/discomfort in haze. PMC

12. Topical corticosteroids (post-op): control inflammation after corneal/glaucoma surgery; taper to limit steroid-induced IOP rise. PMC

13. Cycloplegics (e.g., atropine post-op or for photophobia/uveitis): comfort and synechiae prevention when indicated. PMC

14. Topical antibiotics (peri-op/prophylaxis): reduce infection risk around surgery or contact lens fitting. PMC

15. Lubricants (PF tears/gel/ointment): symptom relief for surface stress; safe long-term. PMC

16. Antifibrotics used intraoperatively (mitomycin-C) or devices with antimetabolites: reduce scarring in trabeculectomy (surgeon-controlled, not home “medicine”). Frontiers

17. IOP-lowering combination drops (e.g., timolol/dorzolamide): simplify regimens; watch combined side effects. Review of Ophthalmology

18. Topical steroids/antibiotic combos after keratoplasty: protect graft and reduce inflammation per surgeon’s protocol. PMC

19. Antiglaucoma meds as temporizing therapy pre-surgery: clear cornea to permit goniotomy/trabeculotomy. Review of Ophthalmology

20. Pain control (acetaminophen/ibuprofen pediatric dosing): comfort around procedures; avoids rubbing/trauma. (General pediatric guidance; surgeon-advised.) PMC

Dietary molecular supplement

Honest note: No supplement repairs ASD or replaces surgery/medical care. Nutrition only supports general eye/child health.

1. Age-appropriate vitamin A (dietary): essential for the ocular surface; avoid overdose from supplements. PMC

2. Omega-3 fatty acids (food sources or pediatric-safe doses): may support ocular surface quality in older children; evidence in infants is limited. PMC

3. Balanced protein/iron/zinc: supports growth and healing around surgeries. PMC

4. Vitamin D within pediatric guidelines: general immune and bone health; no ASD-specific effect. PMC

5. Antioxidant-rich foods (fruits/vegetables): overall health; do not change ASD anatomy. PMC

6. Adequate hydration: supports tear film, especially with contact lenses. PMC

7. Avoid megadose supplements: toxicity risks (e.g., vitamin A); stick to diet-first approach. PMC

8. Breastfeeding/appropriate infant formula: optimal early nutrition when surgeries occur in infancy (follow pediatric guidance). PMC

9. Probiotics (general gut health): no proof for ASD; use only if pediatrician recommends. PMC

10. Post-op nutrition plan: surgeon/pediatrician-guided to promote wound healing and reduce constipation from anesthesia/pain meds. PMC

Immunity-booster, regenerative, stem-cell drugs

There are no approved immune-booster or stem-cell drugs that cure ASD or replace surgery. What exists is surgical tissue–based care and research:

1. Limbal stem-cell transplantation / grafting (surgical, not a “drug”) for severe surface failure in select cases. PMC

2. Cultivated epithelial cell therapies are experimental and not standard for ASD in children. PMC

3. Gene therapy concepts for developmental eye disease are investigational; no ASD-specific clinical therapy today. Taylor & Francis Online

4. Biologic anti-scarring strategies around glaucoma surgery remain under study; routine pediatric use is limited to surgical antimetabolites (e.g., MMC). Frontiers

5. Keratoprosthesis (Boston KPro) is a device-based surgical option for failed grafts/severe opacities, not a drug. EyeWiki+1

6. Tissue engineering of cornea/angle is a research frontier, not a clinical treatment for ASD today. PMC

Surgeries

1. Goniotomy (angle surgery from inside) – opens the blocked/abnormal trabecular meshwork when the cornea is clear enough; first-line for many childhood glaucomas. PMC+1

2. Trabeculotomy (from outside) – preferred when the cornea is cloudy; also first-line. AAO Journal

3. **Trabeculectomy with mitomycin-C or glaucoma drainage device (Ahmed/Baerveldt) – for eyes where angle surgery fails or is not feasible; devices often have better mid-term success in ARS. PMC+2PubMed+2

4. Penetrating keratoplasty (corneal transplant) – to clear central opacities (e.g., Peters anomaly) when vision is threatened; outcomes vary and amblyopia therapy is crucial. PMC+1

5. Boston type-1 keratoprosthesis – artificial cornea for repeated graft failure or very poor prognosis corneas; careful lifelong follow-up is required. EyeWiki+1

Preventions

We cannot prevent a child from inheriting ASD when a causal variant is present. We can prevent vision loss and complications:

1. Genetic counseling + family testing. PMC

2. Early newborn/infant eye exam if a parent/sibling is affected. NCBI

3. Prompt referral to pediatric ophthalmology for any cloudy cornea or abnormal pupil. NCBI

4. Structured glaucoma surveillance plan. PMC

5. Amblyopia prevention (optical correction + patching). PMC

6. Eye protection and rub-avoidance habits. PMC

7. Infection prevention around contact lenses/surgeries. PMC

8. Post-operative adherence (drops, visits). PMC

9. Early low-vision support if needed. PMC

10. Syndrome-specific systemic screening (kidney/heart, etc.). PreventionGenetics

When to see a doctor

Immediately if you see new corneal clouding, constant tearing/light avoidance, a sudden very irritable baby, bulging or rapidly enlarging eye, swollen red eye, or any loss of visual attention. These may signal glaucoma or urgent corneal problems. Babies with known ASD should keep every scheduled visit; missing follow-ups risks permanent vision loss. PMC

What to eat & what to avoid

• Eat: a normal age-appropriate diet with fruits/vegetables (for vitamins/antioxidants), adequate protein/iron/zinc, and diet-based vitamin A. Breastfeeding or proper formula in infancy supports healing around surgeries. PMC

• Avoid: megadose supplements (vitamin A toxicity), “eye cure” products online, and any supplement not cleared by your pediatrician/ophthalmologist—especially around anesthesia or glaucoma medicines. No food or supplement can replace surgery or prescribed drops in ASD. PMC

FAQs

1. Is ASD the same in every child? No—findings and severity vary widely, even in one family. Arizona Genetic Eye Diseases Database

2. Is it inherited? Often autosomal dominant; de novo changes also occur. Genetic counseling helps. PMC

3. Which genes are most common? PITX2 and FOXC1 in ARS; others include PAX6, PITX3, FOXE3, PXDN and more. PMC+1

4. Why is glaucoma so common? The drainage angle develops abnormally, raising eye pressure. NCBI

5. Do drops cure glaucoma? In children, drops are usually temporary aids; angle surgery is mainstay. PMC

6. What surgeries are typical? Goniotomy/trabeculotomy first; trabeculectomy or drainage devices if needed; corneal transplant for dense opacities. Frontiers+2PMC+2

7. What are success rates in ARS glaucoma? Devices and trabeculectomy often outperform angle surgery when ARS tissues are stiff/abnormal. PMC+1

8. Is corneal transplant enough for vision? It can clear the cornea but vision depends on amblyopia therapy and glaucoma control. PMC

9. Is Boston KPro used in kids? Select cases after failed grafts; careful lifelong care needed. EyeWiki

10. Can diet/supplements fix ASD? No—only supportive. Avoid megadoses without medical advice. PMC

11. Will my child need many exams under anesthesia? Sometimes, to safely check pressure/angle when awake exams aren’t possible. NCBI

12. Could other organs be involved? Yes, in some syndromes (e.g., kidney with Pierson, liver/heart with Alagille, dental/umbilical with ARS). PreventionGenetics

13. What about gene therapy or stem-cell drugs? Not available for ASD today; research is ongoing. Taylor & Francis Online

14. Should relatives be checked? Yes—family screening finds milder cases early. PMC

15. What’s the single most important action? Keep scheduled pediatric glaucoma/cornea visits and follow post-op/amblyopia plans. PMC

Disclaimer: Each person’s journey is unique, treatment plan, life style, food habit, hormonal condition, immune system, chronic disease condition, geological location, weather and previous medical  history is also unique. So always seek the best advice from a qualified medical professional or health care provider before trying any treatments to ensure to find out the best plan for you. This guide is for general information and educational purposes only. Regular check-ups and awareness can help to manage and prevent complications associated with these diseases conditions. If you or someone are suffering from this disease condition bookmark this website or share with someone who might find it useful! Boost your knowledge and stay ahead in your health journey. We always try to ensure that the content is regularly updated to reflect the latest medical research and treatment options. Thank you for giving your valuable time to read the article.

The article is written by Team RxHarun and reviewed by the Rx Editorial Board Members

Last Updated: September 19, 2025.

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