In Vivo Confocal Microscopy Study of Pigmented Conjunctival Lesions

Conjunctival melanoma is a potentially lethal neoplasm, with an average 10-year mortality
rate of 30%, and 15-year mortality rate of 45%. This condition occurs mainly in the white
population, with rare reports in black and other non-white populations. Recent studies have
indicated that like cutaneous melanoma, the incidence of conjunctival melanoma is
increasing.

Conjunctival Malignant Melanoma (MM) is also currently diagnosed based upon clinical
grounds, through observation of the growth of the suspected lesions over regular intervals
of time. Unfortunately simple slit lamp examination is currently the only clinical
diagnostic visual instrument available in medical practice, and the early diagnosis of MM by
slit-lamp examination is still rather poor. Further the diagnosis of invasive conjunctival
MM is currently established by conjunctival excisional biopsy and defined by the invasion of
the underlying substantia propria of the conjunctiva by atypical tumor cells, especially
when there is loss of the maturation. Regarding the management of malignant melanoma,
unfortunately the extensive horizontal and even vertical growth of this neoplasm does not
always lend itself to simple excision leading to exenteration. As a vision-sparing
alternative, local excision with cryotherapy has become the treatment of choice. Long-term
follow-up has shown that local recurrences are common. More recently, topical chemotherapy
with mitomycin C (MMC) has been used to treat cases with extensive PAM with atypia , because
the pigmented margin is used as a guide for most conservative treatments, the tumor's edge
may be missed.

Recurrent conjunctival MM often presents as an amelanotic mass and may be mistaken for
pyogenic granuloma in a patient who has had multiple previous excisions of conjunctival MM,
even though the original tumor may have been pigmented. Because of the lack of pigment,
these tumors can remain unrecognized and progressively enlarge, especially if the patient
has had previous surgery and conjunctival scarring. In addition, the tumor margins of
recurrent amelanotic conjunctival MM may be indistinct. These factors can lead to delayed
recognition and the unnecessary need for exenteration. Despite these radical procedures,
which usually lead to loss of vision or the eye, these patients have been shown to have a
poor survival rate, suggesting that metastasis has already occurred at the time of
treatment. This confirms that the extent of the disease at diagnosis is the most important
factor to determine the outcome. Recurrence of conjunctival MM is reported at 26% at 5 years
and, 51% at 10 years.

MM of the conjunctival represents one of the greatest challenges in early or preventive
detection. Whereas surgical excision in early stages of tumor development is almost always
curative, delayed recognition puts the patient at risk of destructive growth and death once
the tumor has progressed to competence for metastasis. Accurate diagnosis of pigmented
lesions of the conjunctiva such as nevi, primary, and secondary acquired melanosis and MM
present a challenge to both the ophthalmologist and the pathologist. It is not possible
clinically to distinguish between PAM with and without atypia. The ability to detect early
MM remains of paramount importance in our efforts to curtail deaths related to this
malignancy. The implementation and utilization of in vivo imaging technologies in clinical
practice would enhance our ability to detect MM while this cancer is in its early stages and
curable. Further, accurate assessment of therapeutic tumor response is critical for
evaluation of chemotherapy results in patients, and in clinical trials. Tumor response is
also a guide for the clinician and patient or study. Early, accurate prediction of
non-response would allow an early change to second-line treatment, thus sparing patient's
unnecessary toxicity, psychological morbidity and delay of initiation of effective
treatment. These are very few variables that investigators, as clinicians, can control
regarding the management of conjunctival MM. However, early detection, technique and time of
surgery may ultimate after tumor recurrence, need for orbital exenteration, tumor
metastasis, and patient death. This non-invasive imaging technique that is now available for
clinical studies might help in early detecting and preventing above mentioned problems.

Inclusion criteria:

1. Age over 18 years

2. The ability to provide informed consent for enrollment in the study

3. Diagnosis of conjunctival nevus (Group 1 only)

4. Diagnosis of racial melanosis (Group 2 only)

5. Diagnosis or suspicion of primary acquired melanosis (PAM), scheduled for biopsy
(Group 3 only)

6. Diagnosis of possible MM scheduled for biopsy (Group 4 only)

7. Confirmed diagnosis of MM based upon clinical and histopathological findings, and
have already undergone resection(Group 4 only)

8. Confirmed diagnosis of MM recurrence based upon clinical and histopathological
findings(Group 4 only)

9. Clear cornea (Group 5 only)

10. No conjunctival lesions or recent conjunctival diseases(Group 5 only)

11. No recent chemotherapy or radiotherapy(Group 5 only)

Exclusion criteria:

1. History of previous ocular surgery within last 3 months

2. History of inflammatory eye diseases within last 3 months

3. Current or history of glaucoma disease and on glaucoma medication

4. Contact lens use within last 3 months

5. Physical inability to cooperate for confocal microscopy

6. Prior history of infectious keratitis within 3 months

7. Suspicion for PAM or malignant melanoma (MM)(Groups 1,2,3)

8. History of PAM or MM(Groups 1,2,3)

9. Histopathology not confirmatory for MM (group 4 only)

10. History of other ocular carcinoma or any recent ocular topical chemotherapy or
radiotherapy (Group 5 only)

11. History of cancer elsewhere in the body which is currently under systemic
chemotherapy (group 5 only)