Ocular surface squamous neoplasia: Is surgical excision necessary?
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Welcome to another edition of CEDARS/ASPENS Debates. CEDARS/ASPENS is a society of cornea, cataract and refractive surgery specialists, here to discuss some of the latest hot topics in ophthalmology.
Our monthly column focuses on ocular surface squamous neoplasia (OSSN), a broad term encompassing a wide spectrum of tumors of the conjunctiva and cornea. The gold standard treatment for OSSN has traditionally been surgical excision. However, in recent years, there has been an increasing trend toward medical therapy as an alternative. Alanna Nattis, DO, and Neda Nikpoor, MD, will discuss how they prefer to manage this condition. Enjoy the debate.
— Kenneth A. Beckman, MD, FACS
OSN CEDARS/ASPENS Debates Editor
Excision remains first-line treatment
Ocular surface squamous neoplasia (OSSN) encompasses a variety of epithelial squamous malignancies, including dysplasia, squamous cell carcinoma in situ and invasive carcinoma.
Traditional treatment for OSSN involves excision using a no-touch technique, often with the goal of achieving at least 3- to 4-mm margins around the lesions, as well as application of absolute alcohol and cryotherapy to the borders of the excision. However, considering the risk for residual microscopic disease beyond the area of excision, adjunctive topical chemotherapy is often used, which is what I do in my practice. Excision of OSSN with adjunctive topical chemotherapy (interferon, 5-fluorouracil or mitomycin C) tends to have the best success rate of all; recurrence has been noted to occur with excision alone, especially when the margins are not clear of neoplastic tissue/cells.
Excisional biopsy offers the advantage of debulking the lesion, achieving clear margins, which decreases the risk for recurrence, and sending out a specimen for definitive diagnosis. In my experience, many patients feel more comfortable knowing that the lesion is being excised from the eye, although there is still a risk for microscopic disease outside of the main lesion location.
There are some instances in which tumor excision may not be possible, including if there is a risk for penetrating deeper ocular structures during surgery, if severely infirmed patients may not be able to get to the operating room or if there are concerns about limbal stem cell deficiency. To avoid these risks, some surgeons prefer to treat solely medically.
As with many aspects of ophthalmology, we have come a long way in terms of diagnostics. Often, the clinical picture can be combined with anterior segment OCT to predict the likelihood of OSSN vs. a benign lesion. Those who are comfortable with this may not perform biopsy and treat empirically with topical chemotherapeutic agents. It is also important to note that although many studies have been performed to evaluate recurrences after medical treatment, there is limited direct and long-term comparison in the literature regarding recurrence rates among surgical and medical treatments. While many surgeons are comfortable performing both excision and treating medically, treatment must always be tailored to the individual patient. In addition, if one is unsure of the diagnosis, it is sensible to perform a careful excisional biopsy to achieve histopathologic diagnosis in order to effectively and properly treat.
- For more information:
- Alanna Nattis, DO, of SightMD New York in Babylon, New York, can be reached at asn516lu@gmail.com.
Chemotherapy should be tried first
In my opinion, there are two main reasons why a surgeon would choose excision rather than topical therapy for ocular surface squamous neoplasia (OSSN).
The first reason is to confirm the diagnosis with an excisional biopsy. However, Carol Karp and others have shown that anterior segment OCT is accurate in allowing us to perform what she called an “optical biopsy.” The characteristic findings of OSSN on OCT are a thickened hyperreflective epithelium with an abrupt transition from normal to abnormal. This is highly specific for OSSN and allows us to make the diagnosis of OSSN without the need for biopsy.
The second reason is failure to respond to topical chemotherapy drops. This may happen, but it is rare. In my experience, almost all cases of OSSN that I have treated have resolved completely with topical chemotherapy drops, and it was only in cases of squamous cell carcinoma that I have needed to perform surgical excision after chemoreduction.
In general, there are three main chemotherapy agents that are used to treat OSSN: interferon, 5-fluorouracil and mitomycin. Interferon is the best tolerated, while mitomycin has the highest toxicity to the ocular surface and is the most likely to cause stem cell deficiency. Unfortunately, topical interferon is not readily available, so I currently use 5-FU for my patients with OSSN. The dosing regimen is one drop four times a day for 1 week, then off for 3 weeks, and repeat until there is resolution of the lesion. I routinely use topical steroids such as loteprednol as needed during the “on” week of chemotherapy drops to help with any redness or irritation. Punctal plugs can also be used to help. In my experience, they are not necessary with 5-FU but are a must with mitomycin.
In general, if I see a patient with OSSN, I take slit lamp photos and perform anterior segment OCT (AS-OCT) through the lesion. Then I will start 5-FU, treat for two cycles and then bring the patient back for an exam, photos and AS-OCT. If the lesion is responding, then I will continue for two more cycles and keep bringing the patient back every 2 to 3 months until complete resolution. In almost all cases of OSSN that I have seen in practice and in my fellowship training at Bascom Palmer with Dr. Karp, the lesions responded to one of these chemotherapy drops, and the patient was able to avoid surgery. Rarely, if there was an aggressive tumor, excision was required. But even in those cases, usually we were able to achieve some amount of chemoreduction before excision. This is beneficial because by reducing the size of the area that needs to be excised, we reduce the amount of damage to the ocular structures and the risk for limbal stem cell deficiency. I believe that all patients deserve a chance with chemo drops before considering surgery.
- References:
- Alvarez OP, et al. BMJ Open Ophthalmol. 2021;doi:10.1136/bmjophth-2021-000842.
- Galor A, et al. Ophthalmology. 2016;doi:10.1016/j.ophtha.2015.06.049.
- Monroy D, et al. Eye (Lond). 2023;doi:10.1038/s41433-023-02434-x.
- Nanji AA, et al. Int Ophthalmol Clin. 2017;doi:10.1097/IIO.0000000000000174.
- Nanji AA, et al. Ophthalmology. 2014;doi:10.1016/j.ophtha.2013.11.017.
- Shields JA, et al. Arch Ophthalmol. 1997;doi:10.1001/archopht.1997.01100150810025.
- Stone DU, et al. Cornea. 2005;doi:10.1097/01.ico.0000138834.42489.ba.
- Tabin G, et al. Ophthalmology. 1997;doi:10.1016/s0161-6420(97)30287-5.
- For more information:
- Neda Nikpoor, MD, of Aloha Laser Vision in Honolulu, can be reached at drneda@alohalaser.com.
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