optic chiasm

Marybeth K. Farazdaghi, William R. Katowitz, Robert A. Avery
- Division of Ophthalmology, The Children’s Hospital of Philadelphia, University of Pennsylvania, Philadelphia, Pennsylvania, USA
- Department of Ophthalmology, The Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, USA
- Department of Neurology, The Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, USA

Purpose of Review:
- Focus on optic pathway gliomas (OPGs), which are low-grade tumors affecting the precortical visual pathways of children and adolescents.
- Discuss the treatment controversy for optic nerve gliomas (ONG), a subgroup of OPGs.
- Summarize recent developments in ONG treatment, emphasizing chemotherapy, molecularly targeted therapies, radiation therapy, and surgery.
Recent Findings:
- Standard chemotherapy remains crucial, but newer molecularly targeted therapies like MEK inhibitors and bevacizumab show promise.
Summary:
- Current and emerging treatments for ONG include chemotherapy, molecularly targeted therapies, radiation, and surgery.

Prevalence:
- OPGs account for 2-5% of childhood CNS tumors; particularly common in children/adolescents.
Origins:
- Can be sporadic or linked to neurofibromatosis type 1 (NF1); 20% of children with NF1 develop OPGs.

Diagnosis:
- Based primarily on neuroimaging (MRI) and clinical examination; sparse tissue biopsy due to associated risks.
Growth Patterns:
- Highly variable; some remain stable while others progress over time. Treatment is considered mainly for progressive vision loss or significant visual acuity decline.

Indications for Treatment:
- Loss of visual acuity and tumor progression on imaging. Significant visual acuity loss defined as 0.2 logMAR or greater.

First-Line Treatment:
- Combination of vincristine and carboplatin; effective with a 3-year progression-free survival (PFS) rate of 77% in NF1.
Alternative Regimens:
- TPCV (thioguanine, procarbazine, lomustine, vincristine) shows promise for sporadic ONGs but has risks for NF1 patients.
Recent Drugs:
- Temozolomide, vinblastine, and vinorelbine used with low toxicity; modest visual improvement noted.

MEK Inhibitors:
- Work on the Ras/Raf/MEK pathway; show efficacy in BRAF mutation cases with a 2-year PFS up to 69%.
Bevacizumab:
- Anti-VEGF agent resulting in visual improvement in refractory cases; effective in both monotherapy and combination therapy.

Usage:
- Once common but now rare due to significant adverse effects on vision and neurocognitive functions; reserved for older patients with limited options.
Modern Approaches:
- New techniques aim to minimize surrounding tissue radiation.

Controversy of Resection:
- Radical surgery is infrequently performed for sporadic ONGs due to potential complications.
Debulking Surgery:
- Indicated in symptomatic cases with significant mass effect; lateral orbitotomy approach can be effective with minimal risk of progression.

Management of ONGs is challenging with the necessity of individualized treatment strategies based on clinical parameters.
Current first-line treatment remains chemotherapy, while newer therapies like MEK inhibitors and bevacizumab are promising for refractory cases.
High morbidity associated with radiation and radical surgery necessitates these treatments as last resorts.

Treatment for optic nerve gliomas is only indicated with significant visual changes or radiological progression.
Standard chemotherapy remains the primary approach, despite modest results.
Molecularly targeted therapies are becoming essential options for those with refractory disease.
Radiotherapy and radical surgery should be approached with caution due to associated risks.
Debulking surgery can provide significant relief in symptomatic patients.

Figure 1: MRI scans highlighting sporadic and NF1-associated optic nerve gliomas.
Figure 2: Post-debulking surgery improvements in a pediatric patient.
Figure 3: Overview of surgical techniques in optic nerve glioma cases.