Juvenile Glaucoma

Glaucoma is a neurodegenerative disorder characterized by progressive optic disc degeneration and visual field loss (see Image. Left Eye Glaucomatous Visual Field Changes). Intraocular pressure (IOP) is the chief modifiable risk factor; periodic tonometric measurements are thus fundamental in managing this disease. Glaucoma is the most common etiology of irreversible blindness. The condition affects over 80 million people globally and is expected to surpass 110 million by 2040.

Glaucoma has 2 main subtypes: open-angle and angle-closure. Juvenile open-angle glaucoma (JOAG) is an uncommon form of primary open-angle glaucoma (POAG) with earlier onset (age 3-40 years), typically with a higher IOP and more severe visual field loss compared with adult-onset POAG. Juvenile glaucoma is often hereditary and significantly influenced by genetic factors, distinguishing it from other forms of glaucoma that primarily affect older individuals. The condition can manifest without an apparent cause and is generally more severe than adult-onset glaucoma. Prompt diagnosis and timely treatment are crucial, as the disease can progress rapidly—leading to significant vision loss.

Many studies report that JOAG typically demonstrates an autosomal dominant inheritance pattern. Mutations in the myocilin (MYOC) gene are well established as part of the genetic etiology of this condition. The MYOC gene regulates the production of the myocilin protein found in the eye's trabecular meshwork; MYOC mutations result in the synthesis of atypical myocilin protein, which builds up in the trabecular meshwork cells. This accumulation hampers the performance of the cells and diminishes aqueous humor drainage, ultimately raising IOP. Other gene mutations reported in this type of glaucoma include CYP1B1, PITX2, and FOXC1.

Anatomy of the Eye

Understanding the etiology of juvenile glaucoma requires knowledge of the anatomical structures involved. The eye is subdivided into anterior and posterior regions (see Image. Schematic of Eye Anatomy). The anterior part is in front of the lens and divides into anterior and posterior chambers. In the posterior chamber, the eye's ciliary body produces a fluid called "aqueous humor." This fluid flows from the posterior chamber into the anterior chamber through the pupil and exits the eye via the trabecular and uveoscleral pathways. Most aqueous humor outflow flows through the trabecular meshwork and the canal of Schlemm, which are parts of the trabecular pathway. In the uveoscleral pathway, aqueous humor passes into the supraciliary and suprachoroidal spaces through the ciliary muscle. Both routes drain the aqueous humor into the venous circulation.

In JOAG, a trabecular meshwork abnormality or deformity frequently reduces the ability of the aqueous humor to flow out, thus increasing IOP. Juvenile glaucoma affects the optic nerve head (optic disc). Elevated IOP leads to gradual optic nerve damage, defined by a reduction in the retinal nerve fiber layer (RNFL) and the loss of optic disc fibers. The damage is permanent and cannot be reversed. If left untreated, the condition can result in visual field abnormalities, eventually leading to total vision loss.