Recent trends in ocular oncology.

New and exciting treatment options have emerged in the field of ocular oncology. Despite these novel therapeutic options, it is important to consider if a new treatment modality is truly beneficial over a proven standard treatment. Various factors such as patient features, tumor features, and benefit–risk potential should be carefully assessed in every individual case to determine which patients or tumors will directly benefit from a specific treatment. Therapeutic options of ocular tumors have evolved from observation, cryotherapy, laser therapy, systemic/intralesional steroids, topical antimetabolites, wide surgical excision, systemic chemotherapy, enucleation, and exenteration to more recent options of systemic/topical beta-blockers, topical imiquimod (IMQ), topical/intralesional interferon alpha-2b (IFNα2b), systemic/intralesional rituximab, photodynamic therapy (PDT), superselective intraophthalmic artery chemotherapy (IAC), gamma knife radiosurgery, and cyber knife radiosurgery over the past few years. Herein, we discuss the recent trends in the management of eyelid, conjunctival, intraocular, and orbital tumors.

Eyelid Tumors

In 2008, Leaute-Labreze et al.[1] discovered the efficacy of oral propranolol in the treatment of infantile hemangiomas (IH) incidentally when oral propranolol was used to combat the adverse cardiac effects secondary to high-dose corticosteroids in two children with severe infantile hemangiomas. Since then, a paradigm shift has occurred in the management of IH, with oral propranolol emerging as a first-line treatment at various centers. There are ongoing efforts to determine the optimal dose and duration of treatment with oral propranolol in IH. The concern about the benefit–risk profile of systemic beta-blockers lead to the successful use of topical beta-blocker (timolol) in the treatment of capillary hemangioma of the eyelid by Guo and Ni.[2]

The use of topical IMQ 5% cream and PDT for various skin conditions has been extensively reported in the dermatology literature. Recently, IMQ has been used successfully in the treatment of periocular lentigo maligna[3] and superficial or nodular basal cell carcinoma (BCC) of the eyelid.[4] IMQ with or without cryotherapy is a useful alternative to surgery in patients with periocular lentigo maligna or BCC when other therapies have failed or contraindicated. However, large size lesions (>1 cm) and patients with compromised immune system may not respond adequately to IMQ.[4] Also, the tolerability and safety of use of IMQ in the periocular region is not adequately determined. PDT with topical methyl aminolevulinate is being successfully used for the treatment of periocular squamous papilloma, squamous cell carcinoma, and basal cell carcinoma, with a response rate of 75% and with minimal damage to surrounding tissues and excellent cosmetic outcome.[5]

Conjunctival Tumors

In more recent years, topical/perilesional injection of IFNα2b has been extensively used for the treatment of ocular surface squamous neoplasia (OSSN). In a recent survey of 81 OSSN tumors treated with IFNα2b by Shields et al.,[6] 95% tumor control was achieved when IFNα2b was appropriately combined with surgical excision. IFNα2b has also been used with variable success in the treatment of primary acquired melanosis, conjunctival melanoma, mucosa-associated lymphoid tissue lymphoma, and Kaposi sarcoma. Personally, we have not found IFNα2b to be effective in control of melanosis or melanoma. On the other hand, IFNα2b has a powerful effect on OSSN. Topical IFNα2b displays a distinct advantage over surgical excision that it coats the entire ocular surface and treats not only the affected site but also the remote preclinical sites, thus potentially eliminating subclinical tumors. In cases of extensive OSSN, PDT can be a useful alternative, and in cases with localized corneoscleral or intraocular invasion, plaque brachytherapy is an effective and well-tolerated modality. From a different perspective, there are several new modalities for conjunctival lymphoma, particularly CD 20+ lymphoma, in that they could respond to systemic or intralesional rituximab.

Intraocular Tumors

For the past 5 years, there has been an increasing popularity of IAC in the treatment of retinoblastoma, with reliable success (tumor control and globe salvage) of group C and group D eyes, and limited success of group E eyes (based on the International Classification of Retinoblastoma).[7] However, the major concerns with IAC are lack of control of potential metastatic disease and possibility for toxicities such as vascular injury, end-organ ischemia, and fluoroscopic-related radiation exposure. In a recent study by Wilson et al.,[8] it was found that the higher the International Classification of Retinoblastoma classification the greater the risk for invasive, potentially metastastic retinoblastoma. In fact, 50% of group E eyes and 15% of group D eyes displayed high-risk histopathological features for metastatic events.[8] Based on our previously published series,[9] untreated high-risk retinoblastoma carries a 24% risk for metastatic disease, and adjuvant systemic intravenous (not intra-arterial) chemotherapy is strongly advised. In cases of group D and E eyes treated with IAC, adequate evidence is not available to comment on whether IAC alone can inactivate retinoblastoma invading choroid, optic nerve, and/or sclera, and thus prevent metastatic disease. Further studies on clinical and histopathological correlation of enucleated eyes post-IAC are recommended.

Recent advances in the treatment of choroidal tumors include the efficacious use of oral propranolol in the treatment of circumscribed[10] and diffuse choroidal hemangioma.[11] However, this deserves further study. PDT has been successfully used for choroidal hemangioma and now it shows favorable results for choroidal metastasis.[12] But, due to limited depth penetration of 689 nm diode laser, PDT is not useful in tumors more than 4 mm in thickness and in tumors with extensive bullous retinal detachment.

Orbital Tumors

Newer modalities in the treatment of orbital lymphoma include intralesional injection of rituximab[13] and cyber knife radiosurgery.[14] Gamma knife radiosurgery provides an effective management strategy in orbital tumors including optic nerve sheath meningioma, optic nerve glioma, schwannoma, orbital metastasis, orbital retinoblastoma, pseudotumors of the orbit, cavernous hemangioma, and lacrimal gland tumors. Oral propranolol has proven successful in the management of orbital IH with a significant tumor size reduction in 80% cases.[15]

In summary, there have been numerous improvements in the detection and management of ocular tumors. Given the rarity of most ocular tumors, many publications are limited by relatively small number of patients and short follow-up. Multicenter trials with larger number of patients and longer follow-up could help to develop a more robust and meaningful index of efficacy.