Main Results

Study (year of publication and number of patients in each study)

IFNa2b

MMC

5-FU

Used Doses

Venkateswaran, et al.  [64]

81.3% resolution (n: 48)

(OSSN)

96.3% effectiveness (n: 54) (OSSN)

5FU 1%, 4x/day for one week/monthly) ultil resolution.

IFN 1 MIU/mL.  4x/day continuously.

Pe’er, et al.

[50]

> 80% (n: 12) (PAM)

Two to five courses of 0.04% (0.4 mg/ml) MMC

Galor, et al. [28]

81% of eyes in the 1 million IU/ml group vs. 92% in the 3 million IU/ml group. (CIN)

10 patients were treated with 1 million IU/ ml of topical IFN-a2b; 9 patients were treated with 3 million IU/ml of topical IFN-a2b. Both groups used 4x/daily

Birkholz, et al. [59]

Significantly reduced prevalence of recurrence (5.9% vs. 66.7%). In positive surgical margins, MMC reduced the tumor recurrence (12.5% vs. 55.6%).   With negative margins, MMC reduced recurrence (0% vs. 83.3%) (OSSN)

Weck cel sponge soaked 0.02% or 0.04% of MMC to the subconjunctival surface at the edge of the surgical excision for 1-3 min. Postop, 1 drop of topical MMC 0.02% 3 times daily for 2 weeks. In most cases, 3 cycles of 2 weeks on and 2 weeks off were used.

Boehm [74]

85% successful rate. (OSSN)

1 million IU/ml 4 times daily until lesion resolution

Zaki, et al. [47]

All eyes showed total cure with no recurrence during the 2-year follow-up period.

Topical cyclosporine A (0.05%) and topical mitomycin C (0.01%) 4 times daily for 12 weeks after surgery.

Shah, et al.  [73]

Complete resolution in 19

tumors (83%). Partial resolution (17%), tumor surface area was reduced 44% (median).

(OSSN)

Topical interferon alfa-2b, 1 million

IU/mL, 4 times daily

B. Damato and SE Couplan [57]

Excision of invasive melanoma

with adjunctive brachytherapy and topical chemotherapy, recurrence occurred in six patients. (if treatment did not include radiotherapy)

(Conjunctival melanoma)

Topical MMC 0.02%, four

times daily for a total of 4 weeks, initially in two 14-day

cycles, separated by a 2-week interval, and latterly in

four 7-day cycles over 8 weeks.

T Finger, et al. (1997) n: 10

Decreased conjunctival pigmentation in the four patients where topical chemotherapy was used as a primary. treatment. Nodular tumors were resistant to topical MMC chemotherapy. (PAM with atypia)

0.04% MMC ophthalmic solution

each week for 28 days. When was used as an adjuvant, drops were given for 7 days starting within 2 weeks of primary excision and cryotherapy

T. Finger, et al. [31]

Patients with T2 and T3 of

AJCC. 2 patients had regression of recurrent disease.

(Conjunctival melanoma)

One drop of interferon alfa-2b (1

million units/ml) was placed into the superior fornix four times daily for three months.

Frucht-Pery, et al. [78]

10 patients had disease-free after one course of treatment. 1 case, residual CCIN remained very small without regrowth. In the one patient with invasive SCC and in 5 patients with CCIN, regrowth occurred after 6 months.

MMC 0.02% to 0.04% four times

daily from 7 to 28 days.

Garip, et al. [32]

Decrease in tumor size after the first cycle 66%, after the second cycle 55%, and after the third cycle 74%. (Melanoma and PAM with atypia)

IFNα-2b, 1 million units/ml, 5 times daily (range 1-6 cycle).

Halas, et al. [52]

Topical therapy after primary excision. No presence of relapse of pigmentation in excision area with or without using MMC during the surgery in patients with PAM.

MMC (0.04% = 0.4 mg/l) as a topic treatment after excision two times for 5 min in the operating room. The patients did not receive MMC fluid for use at home.

Herold & Hintschich [75]

9 patients showed regression and lost pigmentation. 3 patients required a second cycle (PAM with atypia and/or conjunctival melanoma)

5 × 1 drop/day topically for 6 weeks.

Holcombe, et al. [18]

8 of 10 patients achieved clinical resolution from topical IFN-_2b treatment. 1 patient developed invasive SCC

Topical IFNa2b (1 million IU/ml) four times a day until clinical resolution or until the lesion appeared nonresponsive.

Joag, et al. [62]

Complete resolution of OSSN in 82% of patients; 18% were considered treatment nonresponders.

5-FU 1% topically 4 times daily for 1 week followed by a drug holiday of 3 weeks. (Mean: 4 cycles)

Karp, et al. [19]

All patients had complete resolution of the CIN lesion. Mean time to clinical resolution was 11.6 weeks.

Topical IFNa2b million IU/ml four times a day, until clinical resolution.

Kim, et al. [24]

In 72% of giant OSSNs IFNa2b achieved complete control (immunotherapy); there was a

reduction in size (immunoreduction) in 28% of giant OSSNs.

Patients with giant OSSN

was managed with topical IFNa2b (1 million IU/ml) 4 times daily or with injection IFN_2b (a portion of 10 million IU/ml vial)

Krilis, et al (2012) n: 89

Complete resolution of the CIN lesions was in 87 of the 89 eyes treated. (97.75%).

1 million IU/ml drops 4 times daily and retinoic acid 0.01% once every second day.

Kusumesh, et al. [12]

Complete remission of the tumor was observed in 22 patients (91.6%). 8.3% did not respond to the treatment.

Topical IFNa2b (1 million IU/mL) 4 times daily until resolution.

Parrozzani, et al. [63]

Complete regression

was achieved in all patients. Only 3 patients (7.3%) treated with 5-FU alone recurred. Recurrences were successfully treated with additional 5-FU courses.

Topical 5-FU four times/day for 4 weeks (one course until clinical and cytological tumour regression.).

Shields, et al. [24]

Complete tumor regression in 100% of the cases was achive in conjunctival or corneal SCC, even in extensive recurrent tumor

Topical MMC 0.04% one

drop four times daily/1 week followed by 1 week without medication.

Shields, et al. [22]

IFNa2b immunotherapy complete response in 75% Tis, in 100% of T1, and in 70% T3. In combination with surgical excision achieved tumor control in 100% Tis, in 100% T1, in 100% T2, in 100% T3, and in 100%. Topical and/or injection) was used as alone or combined with additional surgery, complete tumor control was achieved 95%.

The topical IFNa2b eye

drops were prepared at a dose of 1 MIU/m. The IFNa2b injection was 1-mL syringe with undiluted Intron-A (10 MIU/mL).

Sturges, et al. [29]

Comparative study: 15 patients elected topical IFNa2b and 14 chose surgical excision. No patient in either group developed a recurrence during the study period (primary OSSN)

Topical INFa2b (1 million U/ml) 4 time per day until clinical resolution.

Vann, et al. [23]

All six patients had complete clinical resolution of the CIN lesion within 6 weeks of initiation of treatment.

Single subconjunctival/perilesional injection of recombinant IFNa2b

3 million (IU) in 0.5 ml and then started topical INFa2b drops (1 million U/ml) four times a day

Prabhasawat, et al.

Before MMC treatment, 6 eyes (85.7%) had recurrences after surgical excision. The tumor-free period ranged from 2 to 19 months. Two patients had multiple recurrences.

Topical 0.002% MMC 4 times

daily. (2-14 cycles)

Ballalai, et al. [45]

Complete resolution of the lesion was achieved in all patients after 1 month of treatment. Recurrence occurred in 1 patient (4.3%) after 24 months of treatment

Topical MMC 0.02%, four times per day, for 28 consecutive days.

Chen, Louis, Dodd, et al. [60]

All the lesions were completely excised superficially from the cornea and limbus with a 2 mm margin on the conjunctival aspect. There was no evidence of clinical recurrence in any cases

Topical MMC 0.04% four times a day per 1-week, at least two courses or after completing epithelial healing.

Sun and Hua [66]

3 years after initiation of treatment complete tumor regression to final visit according to AS-OCT was 32.5 ± 4.2 months (OSSN)

Subconjunctival/perilesional 5 FU injections (mean number of doses 17.0 ± 8.6)

Gichuhi, et al. [67]

Comparative study: Aftersurgical excision of OSSN, recurrences occurred in 11% of 5FU group, and 36% of 47 in the placebo group.

Topical 5FU 1% or placebo four times a day for 4 weeks.