Young girl referred for elevated IOP

Issue: October 25, 2021

ByTeresa P. Horan, MD

BySarwat Salim, MD, FACS

An 11-year-old girl presented to New England Eye Center as an urgent referral from an optometrist for elevated IOP in both eyes.

At the outside practice, she reported difficulty with reading the blackboard at school and was noted to have an IOP of 60 mm Hg and advanced optic nerve cupping in both eyes. This was not noted on earlier exams. Her ocular history was notable for myopia. She had no medical history and reported no allergies or use of any medications. She denied prior eye surgery, laser procedures, use of steroids or eye trauma. Her family history was negative for ocular diseases, including glaucoma. Her social history included being a student and living with her parents.

Examination

On examination, best corrected visual acuity with myopic correction was 20/100 and 20/200 in the right and left eyes, respectively. Refraction was –3.25 +1.00 × 075 in the right eye and –4.00 +1.00 × 157 in the left eye. A relative afferent pupil defect was noted in the left eye. IOP was 52 mm Hg in the right eye and 50 mm Hg in the left eye by Goldmann applanation tonometry. Extraocular movements were full and painless. Slit lamp exam was unremarkable. Of note, no posterior embryotoxon or anterior segment dysgenesis was observed. Gonioscopy was open to the ciliary body band in both eyes with 2+ pigmentation and fine iris processes bilaterally. Central corneal thickness was 538 mm in the right eye and 558 mm in the left eye. Posterior segment exam was notable for 0.9 cup-to-disc ratio in the right eye and 0.95 cup-to-disc ratio in the left eye with cupping of the superior and inferior rims in both eyes. There were no optic nerve hemorrhages noted. The vitreous was clear, and the macula, vessels and periphery were within normal limits bilaterally.

OCT showed global thinning in both eyes with average retinal nerve fiber layer thickness of 52 mm in the right eye and 47 mm in the left eye (Figure 1). Ganglion cell analysis showed thinning in both eyes. Humphrey visual field 24-2 was reliable in both eyes and revealed an inferior arcuate scotoma with developing superior arcuate scotoma in the right eye and a central island in the left eye (Figure 2). Axial length by IOLMaster (Zeiss) was 24.86 mm in the right eye and 25.69 mm in the left eye.

Figure 1. OCT with fair signal strength shows thin RNFL in all quadrants bilaterally with average RNFL of 52 mm in the right eye and 47 mm in the left eye. Ganglion cell analysis with good signal strength shows average thickness of 56 mm in the right eye and 54 mm in the left eye, again with thinning in both eyes. Note that normative data are not available for children younger than 18 years old; hence, there is no normative comparison for our patient’s RNFL.

*Source: Teresa Horan, MD, and Sarwat Salim, MD, FACS*

Figure 2. Humphrey visual field 24-2 with good reliability in both eyes demonstrates an inferior arcuate defect and, to a lesser extent, a superior arcuate defect in the right eye (a) (mean deviation –11.47). In the left eye (b), there is severe constriction with a central island (mean deviation –30.97).

What is your diagnosis?

See answer below.

Elevated IOP

The differential diagnosis for a young patient presenting with elevated IOP and optic nerve damage includes juvenile open-angle glaucoma, late-recognized primary congenital glaucoma, inflammatory glaucoma, steroid-induced glaucoma, angle recession glaucoma and pigmentary glaucoma.

Given the age of presentation and the lack of megalocornea, Haab striae or corneal clouding/scarring, congenital glaucoma was less likely. As the patient did not have a history of steroid use, steroid-induced glaucoma was ruled out. Inflammatory glaucoma was unlikely as there was no anterior chamber cell or flare, keratic precipitates, iris atrophy, or posterior or anterior synechiae noted on exam. Without a history of trauma and normal gonioscopy, angle recession glaucoma was also unlikely. Pigmentary glaucoma was ruled out as the slit lamp exam did not show any evidence of iris transillumination defects or Krukenberg spindle. This 11-year-old girl with newly found elevated IOP, normal gonioscopy and advanced optic nerve cupping in both eyes most likely had juvenile open-angle glaucoma.

Case continued

In the clinic, the patient was treated with acetazolamide 500 mg to lower her IOP as well as multiple rounds of topical glaucoma medications. The IOP was reduced to 33 mm Hg in the right eye and 34 mm Hg in the left eye. She was sent home on dorzolamide-timolol twice daily, brimonidine three times daily, Rocklatan (netarsudil 0.02% and latanoprost 0.005% ophthalmic solution, Aerie Pharmaceuticals) at bedtime in both eyes and acetazolamide 500 mg orally twice daily. The following day, the IOP was 8 mm Hg in the right eye and 9 mm Hg in the left eye. She was maintained on topical medications, and acetazolamide was discontinued. At this visit, medication adherence was emphasized with the family given the severe status of her glaucoma, and potential future surgery was discussed.

At the patient’s 4-month follow-up visit, the IOP was again elevated at 35 mm Hg in the right eye and 42 mm Hg in the left eye. The family said that it was difficult for her to use multiple drops each day and agreed to proceed with surgery. She underwent trabeculectomy with mitomycin C (0.2 mg/mL concentration for 2.5 minutes) in both eyes 1 month apart. Postoperatively, both eyes were treated with topical steroids, antibiotics and atropine. She had an excellent postoperative course, and at postoperative month 4, the IOP remained low at 10 mm Hg in the right eye and 12 mm Hg in the left eye with diffuse, elevated and partially avascular blebs with microcysts in both eyes. BCVA was 20/50 in the right eye and 20/70 in the left eye.

Discussion

Juvenile open-angle glaucoma (JOAG) is a rare form of primary open-angle glaucoma (POAG) seen in patients aged 3 to 40 years old. Most cases of JOAG are inherited in an autosomal dominant pattern, although sporadic cases can occur. Mutations in the MYOC gene coding for myocilin have been linked to JOAG; however, only 10% to 20% of those with JOAG have mutations in MYOC. Pathology of eyes with JOAG has demonstrated thick compact tissue and extracellular deposits in the trabecular meshwork, hypothesized to cause decreased aqueous outflow. These patients often present with elevated IOP, normal-appearing anterior segment and open angle on gonioscopy. Typically, patients are asymptomatic, but some may have blurred vision, pain or vision loss. This differs from late-recognized primary congenital glaucoma because of the lack of megalocornea or Haab striae. Patients with JOAG often have progressive myopia. Given the asymptomatic nature, JOAG is usually detected late, and patients typically present with advanced glaucoma and significantly elevated IOP in the 40 mm Hg to 50 mm Hg range.

The treatment for JOAG is similar to POAG with medical therapy as the first-line intervention. Medical therapy includes aqueous suppressants and prostaglandin analogues. Alpha agonists, such as brimonidine, should be used cautiously in young infants and children as potential adverse reactions include central nervous system depression. Because our patient was 11 years old, we were able to safely use brimonidine before surgery.

As in this case, most patients with JOAG require surgery due to persistently elevated IOP despite maximal medical therapy. Surgical options include trabeculectomy, glaucoma drainage devices, angle procedures and cycloablative procedures. Trabeculectomy is the mainstay of JOAG surgical treatment and effectively controls IOP without the need for additional medications in 50% to 87% of patients at 3 years. However, it may be difficult to achieve long-term IOP control and maintain a well-functioning bleb due to the robust healing response in children. Therefore, intraoperative antifibrotic agents such as MMC are often used. MMC is a better alternative to 5-fluorouracil, which requires postoperative injections. Trabeculectomy combined with MMC has demonstrated a lower IOP compared with trabeculectomy alone. However, antimetabolites should be used with caution as they can increase the risk for hypotony, bleb leak or infection. Tsai and colleagues reported 20% incidence of hypotony maculopathy in the trabeculectomy/MMC group and 0% in the control group at 3 years.

Another treatment option includes glaucoma drainage devices, either valved or nonvalved. In the pediatric population, tube shunt surgery has success rates between 31% and 97%. One study evaluating the Molteno implant (Nova Eye Medical) in patients with JOAG found an 83% success rate at 15 years. Risks of tube shunt surgery in young patients include tube malposition, tube exposure and infection, and strabismus. Angle procedures such as goniotomy and trabeculotomy are less often used for JOAG but can be effective in controlling IOP in the right patient population. Ikeda and colleagues studied trabeculotomy in JOAG and reported 81% success at 5 years and 67% success at 10 years and 15 years. This study also found that patients with congenital glaucoma had a better prognosis than those with JOAG after trabeculotomy. Gonioscopy-assisted transluminal trabeculotomy effectively decreased IOP without adjunctive medications in 70% of cases at 1 year and 59% of cases at 18 months in a retrospective study of 59 eyes with JOAG.

With various treatment options, long-term success is important given the young age of these patients. Upon diagnosis of JOAG, ophthalmologists should counsel the patient and their family on the natural course of the disease, treatment options and need for close follow-up to prevent glaucoma progression.

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For more information:
Teresa Horan, MD, and Sarwat Salim, MD, FACS, can be reached at New England Eye Center, Tufts University School of Medicine, 800 Washington St., Box 450, Boston, MA 02111; website: www.neec.com.
Edited by Allison V. Coombs, DO, MS, and Nisha S. Dhawlikar, MD, MPH. They can be reached at New England Eye Center, Tufts University School of Medicine, 800 Washington St., Box 450, Boston, MA 02111; website: www.neec.com.

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