Supplemental Material:
Case P1:
A 48-year-old male patient had undergone excision and cryotherapy in 2000 due to
PAM with atypia involving the cornea and the bulbar conjuctiva. In July 2005 the
patient presented with a recurrent conjunctival lesion involving superior cornea and
the conjuctiva of the left eye. The biopsy specimen revealed PAM with atypia. 3
months after the surgery, after the complete healing, the photographs were taken
and the residual tumour (253 megapixels; Fig. 2, Pic A) was treated with topical
IFNα-2b for 6 weeks (1 cycle), 5 times daily. In December 2005 regression of the
corneal lesion was documented (183 megapixels) and in February 2006 a second
cycle of topical IFNα-2b was given for 6 weeks. 2 months later, in April 2006 the
tumour area was observed to have regressed further (58 megapixels) and a third
treatment was started in July 2006. After the 3rd cycle of topical IFNα-2b the lesion
was still smaller (47 megapixels), but in comparison to the prior pictures the colour
was darker and due to clinical suspicion of melanoma, another biopsy was
performed. The biopsy specimen revealed PAM with atypia and due to the residual
tumour (12 megapixels), in March 2007, another cycle of topical Interferon (4th cycle)
was started. 2 months later, in May 2007, the tumour size was (Fig. 2, Pic B) almost
the same (10 megapixels) and treatment was stopped. In March 2008, the tumour
size was stable but another lesion in nasal bulbar conjunctiva was detected and
another cycle (5th cycle) of IFNα-2b for 6 weeks was conducted. 6 weeks later a
regression of the tumour area in nasal bulbar conjunctiva (65 megapixels) was seen.
In June 2008, the patient presented with a progression of the presumed conjunctival
and corneal PAM with atypia. A biopsy (Mapping) was done and 4 specimens were
taken. In all specimens PAM with atypia was confirmed. Due to the wide extension of
the tumour, it was not possible to remove the whole tumour, and the residual tumour
(232 megapixels) was treated with topical IFNα-2b. Two months later, in August
2009, there was a significant decrease in size (remaining tumour size: 6 megapixels;
Fig. 2, Pic C) and tumour resolution was seen 3 months after stopping the treatment
in November 2009 (Fig. 2 Pic D). After the tumour resolution the patient was
tumour-free for 12 months.
Case P2:
A 74-year-old female presented with a temporal bulbar conjunctival and corneal
tumour in the left eye. 4 months later in October 2005 she underwent an excisional
biopsy and pathology showed PAM with atypia. Due to the wide extension of the
tumour, the tumour could not be surgically removed completely and a topical IFNα-2b
was started for 6 weeks for the residual tumour (225 megapixels). After the first
cycle, in January 2006, there was a significant decrease in tumour size (9
megapixels). Interestingly 3 months after stopping the treatment, in April 2006, the
tumour resolved completely. In October 2007, the patient presented with a
pigmented lesion in temporal conjunctiva and a recurrence was suspected. The
excisional biopsy revealed PAM without atypia and the patient was tumour-free for
60 months.
Case P3:
A 75-year-old female underwent an incisional biopsy for a nasal conjunctival tumour
(located on the caruncle, plica and fornix) in the left eye. The pathology revealed PAM
with atypia and due to the residual tumour after the surgery (212 megapixels) in
October 2006, therapy with topical IFNα-2b for 6 weeks was started. After the 1st
cycle there was a very small decrease in size of the tumour (173 megapixels), but the
colour of the tumour was darker and change into conjunctival melanoma was
suspected. Another incisional biopsy was performed and the pathology revealed PAM
with atypia. Due to the wide extension of the tumour, the whole tumour could not be
removed and the residual tumour (70 megapixels) was treated again with topical
IFNα-2b. Two months later, in July 2007, regression of the tumour was documented
(6 megapixels). In September 2009, another biopsy was performed and pathology
revealed again PAM with atypia.
This patient had lost her other eye previously due to a postoperative endophthalmitis
and the visual acuity of this eye was no light perception. For this reason, we
performed a biopsy after every treatment to detect the change into melanoma if
present, as early as possible.
Case P4:
A 58-year-old female underwent an excisional biopsy for a conjunctival tumour
located in tarsal conjunctiva of the upper lid. The pathology revealed PAM with atypia.
6 years later, in January 2008, treatment with topical IFNα-2b was initiated for
presumed recurrent conjunctival PAM with atypia (91 megapixels). 2 months after
starting the treatment there was a regression in tumour size (25 megapixels) and
therefore the patient was conducted to continue the treatment for another 6 weeks.
In April 2008 there was again a regression in tumour size (10 megapixels). 4 months
after stopping the treatment with IFNα-2b, there was a complete tumour resolution
and this patient remained tumour-free for 29 months.
Case P5:
A 75-year-old male patient presented with a multifocal tumour including cornea,
tarsal conjunctiva and the lid margin. This patient underwent 2 excisions, passow
cautery, and cryotherapy prior to the IFNα-2b treatment. In July 2004 another
biopsy was performed due to a recurrence and 4 specimens (3 conjunctival, 1 dermis
specimen) were taken. The pathology revealed PAM with atypia in tarsal conjunctiva
of the lower lid and nasal bulbar conjunctiva. Dermis specimen and cornea specimen
showed no atypia. 3 months later a topical IFNα-2b treatment was initiated, but
unfortunately due to the loss of this data, the change in tumour size could not be
compared. In June 2008, due to a presumed recurrent PAM with atypia, another
excisional biopsy was performed. The pathology confirmed the PAM with atypia.
There was only a residual tumour in the cornea (74 megapixels) (Fig. 1, Pic. A) and a
2nd cycle of topical IFNα-2b for 6 weeks was started. 3 months later the tumour was
completely resolved (Fig. 1, Pic. B) and his last visit was one month after the
treatment and the conjunctiva was tumour-free.
Case M1:
A 64-year-old male underwent an excisional biopsy elsewhere for a conjunctival
melanoma in the right eye. Five years later, he presented with a presumed recurrent
conjunctival melanoma, another excisional biopsy was performed and 4 specimens
were taken. Two specimens showed PAM with atypia, one specimen showed
conjunctival melanoma, and one specimen showed chronic inflammation. Due to the
wide extension of the tumour, the whole tumour could not be removed. One month
later a topical IFNα-2b treatment for 6 weeks was initiated due to the residual tumour
(237 megapixels) after the surgery. 2 months later there was a significant decrease in
tumour size (5 megapixels). Eight months later, in his last visit, there was no tumour
resolution, but the size of the tumour was stable (5 megapixels).
Case M2:
A 65-year-old female underwent an incisional biopsy (Mapping) for a multifocal
conjunctival tumour including the fornix of the lower lid and the plica in the right
eye. Three specimens were taken and pathology showed in 2 specimens (fornix and
plica) PAM with atypia and 1 specimen (temporal fornix) showed conjunctival
melanoma. Due to the wide extension of the tumour, the tumour could not be
removed completely. One month later, topical IFNα-2b treatment was initiated due to
the residual tumour after the surgery (193 megapixels). After the first cycle of topical
IFNα-2b treatment, there was a decrease in tumour size (62 megapixels). Due to the
good response to treatment, another cycle of topical IFNα-2b was started.
Unfortunately the data was lost and the size change could not be calculated before and
after the second cycle. 7 months after the end of the second cycle of topical IFNα-2b,
a progression in size of the conjunctival lesion was detected and pathology revealed
PAM with atypia. One month later, after the complete healing of the conjunctiva due
to the residual tumour (14 megapixels) a third cycle of topical IFNα-2b was
conducted for 6 weeks.
Two months after starting the topical treatment the tumour resolved completely and
the patient was tumour- free for 13 months.
Case M3:
A 61-year-old female underwent an excisional biopsy with passow cautery in 2004
for a temporal located conjunctival and corneal tumour in the right eye. The
pathology revealed PAM with atypia. In June 2006 the patient presented with
recurrence (tumour size: 83 megapixels) of presumed PAM with atypia and the first
cycle of IFNα-2b for 6 weeks was started. Two months later, the regression of the
tumour was documented (57 megapixels). Unfortunately, 3 months later there was a
progression in tumour size (93 megapixels) and a 2nd cycle of IFNα-2b was
conducted. In January 2007, there was a small decrease in tumour size (78
megapixels). Ten months later, due to a progression in tumour size and change in
colour, an excisional biopsy was performed. The pathology revealed a melanoma of
the conjunctiva. After the surgery another topical IFNα-2b treatment was started, but
unfortunately the data was lost and the tumour size could not be calculated before
and after the treatment. This patient had to be operated due to the failure of the
topical IFNα-2b treatment.
Case M4:
A 62-year-old female underwent 2 excisions and a treatment with passow cautery
due to her conjunctival melanoma located in nasal bulbar conjunctiva. In December
2005 a recurrence of the tumour in bulbar conjunctiva and a local metastasis in the
nasal tarsal conjunctiva were detected. The patient underwent an incisional biopsy
(Mapping) and 3 specimens were taken (2 from forniceal- and one from bulbarconjunctiva). The pathology revealed a conjunctival melanoma in all specimens. Due
to the multifocality and the wide extension of the tumour, the residual tumour in
tarsal conjunctiva (24 megapixels) was treated with IFNα-2b. Five months later, in
May 2006, there was a decrease in tumour size of the tarsal conjunctiva (8
megapixels), but a new-pigmented lesion in bulbar conjunctiva was documented. The
bulbar and tarsal lesions were removed surgically and pathology revealed PAM with
atypia. In October 2007 there was a small pigmented lesion in tarsal conjunctiva
(tumour size: 40 megapixels), a recurrence was suspected and a second cycle of
topical IFNα-2b was conducted.
6 weeks later, there was a regression in tumour size (tumour size: 28 megapixels),
but another lesion of the bulbar conjunctiva was detected and in January 2008
another excisional biopsy was performed. The pathology showed PAM with atypia
and the third cycle of IFNα-2b was started for the residual tumour. Due to the loss of
the data, the tumour size could not be calculated and compared before and after the
third cycle of IFNα-2b. In 2009 and 2010 this patient underwent 2 excisions because
of the recurrence of the tumour and the pathology in 2010 revealed a melanoma with
clear margins. This patient was operated several times due to the failure of IFNα-2b
treatment. However, compliance with IFNα-2b therapy was difficult to sustain due to
the patient's psychological problems.
Case M5:
A 61-year-old male underwent 5 excisions and twice in combination with
cryotherapy due to the recurrent melanoma of the conjunctiva. In 2006, a recurrence
detected on the bulbar conjunctiva and an incisional biopsy was done. The pathology
revealed a melanoma of the conjunctiva and 3 weeks later the first cycle of IFNα-2b
was started for treatment of the residual tumour (8 megapixels). Three months after
starting the treatment, there was a regression in tumour size (1 megapixel) and
interestingly 8 months after stopping the treatment, the tumour resolved completely
and the patient was tumour- free for 40 months.
Case M6:
A 45-year-old female underwent an excisional biopsy for presumed conjunctival and
corneal melanoma extending from 10h-12h-4h in the bulbar conjunctiva of the left
eye. Pathology confirmed the diagnosis. Due to the wide extension of the tumour, the
small size of residual tumour located at the temporal limbus (6 megapixels) was
treated with topical IFNα-2b for 6 weeks. Two months later there was a significant
decrease in tumour size (0.1 megapixels). Three months later, in December 2007, a
new-pigmented lesion was detected in the nasal bulbar conjunctiva and a local
metastasis was suspected. The whole tumour in the nasal bulbar conjunctiva was
removed surgically and the pathology revealed a conjunctival melanoma with clear
margins. One month later, for the tumour in the temporal bulbar conjunctiva, a
second cycle of topical IFNα-2b was conducted. This lesion stayed stable in size (0.1
megapixels) and colour after the treatment and until the last visit in July 2010.
Case M7:
A 39-year-old female underwent an excisional biopsy for nasal bulbar conjunctival
and corneal tumour in the right eye. The pathology revealed a melanoma. Four
months later, first cycle of IFNα-2b was started due to a residual tumour after surgery.
Due to the lack of precise documentation the size change before and after the first
IFNα-2b treatment could not be compared. In July 2007, progression in size of the
tumour was documented and a second cycle of IFNα-2b (tumour size before
treatment: 15 megapixels) was given. Three months later there was a very small
decrease of tumour size (13 megapixels). In January 2008, also change in tumour
colour was documented and another excisional biopsy was done. The pathology
revealed PAM with atypia. One month later, the third cycle of IFNα-2b was started for
the residual tumour (5 megapixels). In May 2008 the tumour resolved completely.
Unfortunately in 2010 this patient underwent a neck dissection and parotidectomy
due to the metastasis of the melanoma.