By Daniel Schrempp   |  PCLI—Lewiston, ID

Ami Halvorson, OD

 

PCLI—Portland, OR

From the EDITOR   As our scope of practice increases, it is important for optometric physicians to participate in and remain current with an ever widening range of medical services. In this issue, my colleague Daniel Schrempp provides tips for diagnosing and treating ocular surface squamous neoplasia—an often asymptomatic but serious condition.

Optometry is expanding in scope and sequence to meet the growing demands of an aging population. According to the American Optometric Association, ODs now deliver 85% of primary eye care in America. As this expansion continues, we must prepare to diagnose and participate in treating more uncommon ocular pathologies.

BE VIGILANT

We especially need to improve our ability to recognize conditions that can only be identified through careful routine eye exams. In this article, we’ll discuss one such group of often asymptomatic diseases known as ocular surface squamous neoplasia (OSSN).

DEFINITIONS

OSSN encompasses a wide range of dysplastic changes to the corneal epithelium, limbus, and conjunctiva. Simply put, they are unhelpful distortions in adult cells’ size, shape, and organization.

Changes of this type can rapidly coalesce and form neoplasias—tumors or masses of abnormal cells that proliferate without control and serve no useful biological function.

These ocular surface tumors are imperfectly separated into two main subgroups:

1.  Conjunctival Intraepithelial Neoplasia (CIN)

• Non-invasive
• Dysplastic cells of these tumors remain above the basement membrane
• Often considered the precursor to SCC

2. SQUAMOUS CELL CARCINOMA (SCC)

• Malignant
• Penetrating through the basement membrane, gaining metastatic or spreading potential
• It should be considered more serious

ETIOLOGY

The dysplastic cells of OSSN are believed to emerge from limbal stem cells in susceptible patients. Not surprisingly, risk factors are multifactorial. They include:

•  History of heavy smoking
•  Lighter complexion
•  Vitamin A deficiencies
•  History of extensive UV exposure
•  History of extensive petroleum
  product exposure

The incidence of OSSN in younger patients has also been associated with HIV infections.

DIAGNOSIS

While biopsy is the only absolute identifier of any histological condition, it should generally be avoided with limbal lesions like OSSN. In these cases, biopsy runs the unnecessary risk of limbal stem cell damage and a higher long-term risk of limbal stem cell deficiency (LSCD).

 

 

 

 

 

 

 

Thankfully, at the slit lamp, both OSSN sub-groups present with clinical markers that can assist in correctly diagnosing and categorizing these tumors.

CIN

•  They are less scary-looking.
•  Have a gelatinous or white surfaced appearance.
•  Have hairpin-type intralesional vessels.

SCC

•  They look angrier and more aggravated.
• Present with “red-dot” or “strawberry” type papillomatous patterns.
• Another helpful indicator for basement membrane violation, and therefore SCC, is the presence of larger feeder vessels.

Treatment itself can be diagnostic as the more common masquerading conditions of pterygium, pinguecula, and pannus do not respond to our primary therapeutics.

Treatment

Over the last several decades, OSSN has evolved from mainly a surgical disease to primarily a medically treated condition. Treatment now almost always starts by employing the use of chemotherapy eye drops—Mitomycin C (MMC) or 5-Fluorouracil (5-FU).

The most significant advantage to using these powerful chemicals first over the more invasive limbal excision surgery is their ability to completely eradicate invisible tumor cells that even the best surgeons inevitably leave behind.

MMC and 5-FU each have specific nuances. It is always helpful to work with a corneal specialist to decide which compounded drops will be best for your unique case.

CHEMO EYE DROPS

MMC is isolated from Streptomyces caespitosus. Once activated, the alkylating properties form free radicals that interact with and impair DNA synthesis. MMC is our fastest option for treating OSSN.

The downside of MMC’s therapeutic expediency is a higher incidence of substantial side effects. These include pain, severe epitheliopathy, punctal-canalicular stenosis, and limbal stem cell damage.

Standard MMC treatment includes:

• An eye drop concentration of 0.02 percent.
• Drops are installed four times daily in cycles of two weeks “on” and two weeks “off.”
• Extending treatment with MMC past two cycles should be considered with extreme caution due to its higher risk of LCSD.
• Placing punctal plugs when using MMC is essential to prevent stenosis and improve ocular surface contact.

 

 

 

 

 

 

 

5-FU is also an excellent option and a favorite among corneal specialists. It is an antimetabolite that blocks thymidine synthase and a tumor cell’s ability to make essential proteins.

Though slower acting than MMC, 5-FU has the same efficacy but with less severe adverse impact. However, irritation, mild epitheliopathy, conjunctivitis, and photosensitivity are common.

Typical 5-FU treatment consists of:

• One percent eye drops used four times a day for one week “on” followed by three weeks “off.”
• Another significant advantage of 5-FU over MMC is the clinician’s ability to confidently use more than two cycles for larger or more stubborn tumors without the risk of substantial long-term complications.

Topical steroids and preservative-free tears can be co-administered with MMC and 5-FU to reduce discomfort.

CONCLUSION

In treating OSSN, topical chemotherapy eye drops have become a well-established, safe, and effective alternative to excisional surgery alone. Through careful and diligent primary eye care, the modern OD can now play an essential and satisfying role in the diagnosis and treatment of this often asymptomatic but serious condition.