Juvenile open-angle glaucoma (JOAG) is characterized by elevated intraocular pressure (IOP) in patients between the ages of 5 and 35, resulting in optic nerve thinning and loss of peripheral vision.
In comparison to the more insidious adult-onset primary open-angle glaucoma (POAG), JOAG is often severe and rapidly progressive.1
Clinical features of JOAG
Individuals with JOAG may have a significant family history, with an estimated 10% of cases associated with an autosomal dominant, missense mutation in the myocilin (MYOC) gene within the GLC1A locus (formerly known as the trabecular meshwork-inducible glucocorticoid response protein or TIGR) on chromosome 1Q.2-5 Myocilin is a highly expressed protein within the trabecular meshwork (TM).6
Genetic mutations
The mutated MYOC protein cannot be secreted and instead accumulates within the cell’s endoplasmic reticulum, altering the shear stress response of the trabecular meshwork and increasing resistance to aqueous humor drainage, causing the characteristically high IOP of JOAG.2,4-7
Homozygous and compound heterozygous mutations in the Cytochrome P450 1B1 (CYP1B1) gene have also been linked to JOAG, with one study on an Australian cohort concluding that patients with enriched CYP1B1 pathogenic variants had a more severe and advanced form of JOAG.8-10
CPAMD8 mutations were established in a different Australian study to have a high correlation with JOAG, iris abnormalities, and cataracts.11,12 Other mutations that have been reported to cause JOAG include heterozygous FOXC1, TBK1, COL2Z2, and OPTN mutations.11,13
Additional risk factors
There is also a correlation between a history of high myopia and glaucoma, with one study of five pedigrees reporting that 87% of affected individuals were myopic.1,2,8 Glaucoma is both more common and more challenging to diagnose in high myopes, especially when evaluating optic disc appearance. JOAG progression is also associated with a faster myopic shift over time.
While some cases of JOAG arise in patients with a positive family history, there are reports of a de novo MYOC mutation in a 14-year-old Australian male,14 and two additional cases in the USA and China with two unique de novo heterozygous MYOC mutations inherited from the mothers via an autosomal dominant pattern to the probands.15,16
Management protocol for JOAG
JOAG is a distinctively different disease from primary congenital glaucoma, with an age of onset classically after early childhood.
The absence of the following clinical characteristics can aid in differentiating JOAG from primary congenital glaucoma:1,2
- Buphthalmos
- Increased corneal diameter
- Haab’s striae
- Corneal haze
Due to its relative rarity in childhood and lack of externally obvious signs or symptoms, patients with JOAG can have severe vision loss at initial presentation.
Topical medications
Many patients with JOAG are refractory to intraocular pressure (IOP) control via maximum topical eye drops, requiring surgical management of IOP.1
One study reported that 15 out of 17 (88%) JOAG patients required some level of surgical management, and another study in Hong Kong reported that 15 out of 22 JOAG eyes (68%) had surgical or laser management.17,18
Filtrations/drainage
A variety of traditional filtration and drainage interventions are typically performed depending on IOP, age at surgery, and other clinical decision-making factors.
A US-based retrospective study on the treatment patterns of JOAG reported that patients underwent the following procedures (from most to least common):19
- Laser trabeculoplasty: 74.1%
- Filtration surgery: 47.5%
- Angle surgery: 25.8%
- Tube shunt: 15.9%
- Cyclodestruction: 15%
MIGS
With the development of minimally invasive glaucoma surgery (MIGS) and the level of risk and complications associated with traditional filtration surgery, angle surgeries are gaining traction as the preferred method of management for open-angle glaucoma.20,21
A retrospective Chinese study on GATT on 59 eyes showed a statistically significant reduction in IOP and medications from 26.5±9.0mmHg on 3.7±0.9 medications to 14.7±3.0mmHg on 0.7±1.2 medications, with no statistically significant difference in eyes with or without previous surgical history.22 However, a different retrospective study in 90 patients reported that patients with high myopia have higher chances of failure of GATT, although statistical significance was not reached.23
Goniotomy has also been proven to be a safe and successful method of management of JOAG, with one US-based study on 17 eyes showing an average IOP reduction from 32.3± 6.7mmHg to a post-operative IOP of 19.5±8.6 mmHg.24
Canaloplasty can also be performed to enhance the natural drainage into Schlemm’s canal in patients with mild to moderate open-angle glaucoma.25 A study by Khaimi et al. recorded 57 of 58 (89%) open-angle glaucoma eyes had a decrease in IOP and 44 of 58 (69%) eyes required fewer medications.26
In eyes refractory to other forms of management, or eyes with low visual acuity, cyclophotocoagulation can be an effective form of treatment to decrease the number of ciliary bodies producing aqueous humor.27,28 Laser trabeculotomy can also be performed for a moderate reduction of IOP.28,29
Case Report: Myopia, decreased vision, and elevated IOP
A 15-year-old male, with a negative family history, was referred to our clinic with elevated eye pressure and decreased visual acuity. He had seen his eyecare provider earlier in the month for an annual exam for high myopia, and vision was unable to be improved with refraction from count fingers (CF) at 4 feet in his right eye (OD).
The exam one year prior had been 20/20 with correction in both eyes (OU). Referral to an outside ophthalmologist revealed elevated IOP in both eyes. Subsequently, he was referred to our team for complex pediatric glaucoma care.
The patient had no family history of any blinding eye disease, and no personal history of trauma or medical problems. He was a healthy and active 15-year-old.
Physical exam
On physical exam:
- Visual acuity was CF at 4 feet OD
- Left eye was 20/20 in updated myopic correction
- Confrontational visual field (CVF) via finger count
- Dense field loss with only a temporal island remaining OD
- Full CVF OS
- Positive afferent pupillary defect (APD) OD
Tonometry with the iCare:
- IOP was measured to be 46mmHg OD and 36mmHg OS
- Unable to applanate at this time due to severe blepharospasm OU
Other findings:
- Gonioscopy and pachymetry were similarly unsuccessful
- Slit lamp exam (SLE) was unremarkable, with deep anterior chambers
- No evidence of inflammatory disease, corneal pathology, or buphthalmos
- The right optic nerve was observed to be pale, with a cup-to-disc ratio (CDR) of 0.95 OD and 0.5 OS
- Fundus exam and findings were consistent with a history of high myopia in both eyes
Figures 1 and 2: Fundus photographs of the patient’s optic discs OD and OS, respectively.
Figure 1: Courtesy of Courtney Kraus, MD.
Figure 2: Courtesy of Courtney Kraus, MD.
Table 1: Summary of key clinical features of the patient.
Table 1: Summary of key clinical features of the patient.
| OD | OS | |
|---|---|---|
| Average RNFL Thickness | 54μm | 74μm |
| RNFL Symmetry | 20% | 20% |
| Rim Area | 0.36mm² | 1.02mm² |
| Disc Area | 3.08mm² | 2.60mm² |
| Average C/D Ratio | 0.83 | 0.77 |
| Vertical C/D Ratio | 0.95 | 0.72 |
| Cup Volume | 1.344mm² | 0.597mm² |
OCT imaging revealed significant thinning globally OD at 54μm. Significant and deep cupping was visualized. The left eye also demonstrated neuroretinal rim thinning, particularly vertically. It is noted that imaging quality was poor, and we were unable to obtain better quality OCT imaging.
Figure 3: Optical coherence tomography (OCT) imaging OU of the optic nerve head (ONH) and retinal nerve fiber layer (RNFL).
Figure 3: Courtesy of Courtney Kraus, MD.
Clinical management
The patient was prescribed maximal topical eye drops, including dorzolamide / timolol, brimonidine, and latanoprost, and surgery was scheduled within the week. Recheck of IOP showed insufficient IOP reduction on this regimen. Due to our patient’s low visual acuity in his right eye, diode cyclophotocoagulation was performed.
During examination under anesthesia, IOP was checked before induction using Tono-pen (Reichert Technologies). IOP was 36mmHg in the right eye and 24mmHg in the left eye, with the use of max topical treatment that morning. Pachymetry measured 613 microns on the right eye and 587 microns on the left eye.
Axial length was 28.92mm in the right eye and 28.03mm in the left eye. Gonioscopy revealed open angle to posterior TM in the right eye and open angle to posterior TM and some CB visible with patchy PAS in the left eye.
In his left eye, a 360° canaloplasty and inferior 180° goniotomy were performed using the OMNI Surgical System (Sight Sciences). The patient did well in his immediate post-operative course. Two months after bilateral surgical procedures, his right eye IOP has been well controlled on four classes of IOP-lowering medications, with a max IOP of 18mmHg (iCare).
Visual acuity has improved to 20/400 utilizing eccentric fixation. In the left eye, he continues to use dorzolamide / timolol, which has allowed a post-operative Tmax of 15mmHg by iCare. Visual acuity remains 20/20 with correction. Genetic testing is still pending at this time.
Conclusion
Patients can present with JOAG with severe loss of visual acuity and exceedingly high IOP. While JOAG patients may present with a positive family history, there have been reports of sporadic de novo mutations and reduced penetrance, such as ours, that make JOAG a critical diagnosis to include in the differential.
The clinical management of JOAG is complex, with various therapeutic management paths depending on IOP, age of the patient, and other clinical decision-making factors.
Therapy aims to both reduce IOP, preventing further nerve damage and irreversible vision loss, and to reduce the number of topical eye drops needed daily.
