Peds Ophtho Case 3: Diagnosis & Conclusions

Diagnosis: Primary Congenital Glaucoma, likely infantile onset (>1-24 months)

Primary congenital glaucoma (PCG) is a rare developmental glaucoma that arises from genetic abnormalities in the trabecular meshwork and anterior chamber angle. These abnormalities  impair drainage of the aqueous humor, causing increased intraocular pressures (IOPs). 

PCG is typically diagnosed within the first year of life and all patients with suspected PCG require immediate referral to ophthalmology. In contrast to adult-onset glaucoma (i.e. primary open-angle glaucoma) which can have a more insidious onset with irreversible damage to the optic nerve, infants have more elastic ocular structures, resulting in damage to multiple eye structures and thus more overt manifestations of symptoms. More specifically, increased intraocular pressure in infant eyes leads to stretching of the sclera and cornea, which contributes to the characteristic enlarged globe or buphthalmos, and megalocornea (enlarged cornea), in eyes with PCG.  The damage can be reversible or irreversible depending on severity of disease and treatment timing. PCG’s classic “triad” of symptoms includes photophobia, epiphora, and blepharospasm. These symptoms arise from corneal edema induced by the  acute elevation inIOP. Significant corneal edema can create an opacified corneal appearance, .often described as a haze or “blue tint.” 

Though most cases of PCG are sporadic, up to 40% of cases are familial and individuals with a positive family history of PCG are at increased risk. Five risk loci have been associated with PCG (GLC3A-D). Notably, approximately 20% of cases in the U.S. have been associated with a CYP1B1 mutation, which is located on the GLC3A locus. Certain syndromes can also present with childhood glaucoma, including Axenfeld-Rieger Syndrome and Sturge-Weber syndrome.

Pearls for the Pediatrician

Examination should include evaluation of vision, external structures including the cornea, and intraocular pressure. 

A thorough corneal exam includes measuring the corneal diameter which is often larger in the affected eye due to buphthalmos. Corneal exam may also demonstrate Haab’s striae, or horizontal curvilinear breaks in Descemet’s membrane (see image on left). These should not be confused with vertical corneal striae, or Vogt’s striae, which are caused by forceps injury during delivery.  (Upper left image credit: © American Academy of Ophthalmology)

While assessment of intraocular pressure can be challenging in these young patients or if equipment is not available, intraocular pressures can be estimated through simple palpation over closed eyelids. In unilateral or asymmetric disease, the eye with higher intraocular pressure will feel more firm. 

Pearls for the Ophthalmologist

Of note, some children may born with larger corneas, termed megalocornea. This condition is generally present in birth, bilateral, more common in boys and generally benign. Congenital Hereditary Endothelial Dystrophy (CHED) is another condition that may present similarly to PCG. CHED is an inherited condition that presents at birth or during infancy and is characterized by bilateral corneal opacifications due to fewer endothelial cells. Thhis leads to corneal edema and opacification with consequent visual impairment and nystagmus. In contrast to PCG, CHED is not typically associated with increased IOPs. 

Work-up for PCG includes a standard ophthalmologic exam with particular emphasis on signs of increased intraocular pressure. As discussed above, this includes measuring the corneal diameter and assessing for Haab’s striae, or horizontal  curvilinear breaks in Descemet’s membrane Haab striae are best visualized with retroillumination (see image on left). Dilated fundoscopy should look for signs of glaucomatous optic neuropathy, including an enlarged or asymmetric cup-to-disc ratio and rim loss. As buphthalmos and Haab’s striae cncan cause myopia and astigmatism, respectively,, cycloplegic retinoscopy should be done to evaluate and correct any associated refractive error. (Upper left image credit: © American Academy of Ophthalmology)

IOP can be measured using a Tono-pen, iCare rebound tonometer or Goldmann applanation tonometry. Gonioscopy should also be done to visualize the iridocorneal angles. An A-scan ultrasound may also be performed to determine axial length measurement, which is expected to be longer in buphthalmic eyes. Exam under anesthesia is typically required to perform a complete ophthalmic exam in these young patients. If the patient is old enough to be examined using a regular slit lamp, pachymetry to measure central corneal thickness and optical coherence tomography are additional tests that may be considered.

Treatment

Similar to adult-onset glaucoma, goals of therapy include lowering IOP to prevent optic nerve damage.. However, while medical management is often first-line for adult-onset glaucoma, surgery is the main method of treatment in patients with PCG. In PCG, surgery aims to re-establish outflow of aqueous humor as the trabecular outflow system abnormal in these eyes. This ccan be be accomplished with angle surgeries such as goniotomy or trabeculotomy, or with trabeculectomy, which bypasses the native outflow system. Evidence has shown similar rates of success between goniotomy and trabeculotomy. Furthermore, patients with infantile glaucoma (onset 1-24 months of age) tend to have better outcomes than those with neonatal-onset and late-onset glaucoma. In cases refractive to the above surgical techniques, glaucoma implant surgery and cycloablation are alternative surgical options. IOP-lowering medications can be used as an adjunct or short-term bridge to surgery.

References and Additional Resources:

  1. Abu-Amero KK, Edward DP. Primary Congenital Glaucoma. 2004 [Updated 2017 Aug 17]. In: Adam MP, Ardinger HH, Pagon RA, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2021.
  2. Anderson DR. Trabeculotomy compared to goniotomy for glaucoma in children. Ophthalmology. 1983;90(7):805-6.  
  3. Bettman JW, Cleasby GW.  Congenital glaucoma. Pediatrics. 1963;32(3): 420-424.
  4. Clark RA, Freedman SF, Wong MO, et al., Primary Congenital Glaucoma Loh AR (Eds). American Academy of Ophthalmology: EyeWiki. December 2020.
  5. Chen TC, Chen PP, Francis BA, Junk AK, Smith SD, Singh K, Lin SC. Pediatric glaucoma surgery: a report by the American Academy Of Ophthalmology. Ophthalmology. 2014;121(11):2107-15. 

Case 3 Index

Peds Ophtho Case 3 Index
Peds Ophtho Case 3: Introduction
Peds Ophtho Case 3: Additional History & Physical Exam
Peds Ophtho Case 3: Ophtho Visit and Exam
Peds Ophtho Case 3: Case Continued…