Jovanovic, Nina; Russell, William W.; Heisel, Curtis J.; Hood, Christopher T.; Kahana, Alon
Conjunctival cicatrizing conditions are vision threatening, with poor outcomes despite aggressive systemic therapy. This study tests the utility of serial injections of 5-fluorouracil (5-FU) into the fornices to treat conjunctival scarring in patients with ocular cicatricial pemphigoid or Stevens–Johnson syndrome/toxic epidermal necrolysis.
Retrospective cohort study. Fisher exact test and multivariable logistic regression analyses were used to compare clinical outcomes of patients who were administered 5-FU injections versus patients who were not injected. Model fit was examined for multivariable regression.
One hundred twelve eyes (56 patients) met the inclusion criteria. Thirty-eight eyes (34%) had Stevens–Johnson syndrome/toxic epidermal necrolysis, and 74 eyes (66%) were diagnosed with ocular cicatricial pemphigoid. Twenty-five eyes received ≥1 injection of 5-FU. Sixteen eyes received 1–4 injections, while 9 received ≥5. Median follow-up until last encounter was 18 months. Analysis of each disease entity alone and in combination revealed that 5-FU injections were associated with improvement in final visual acuity, corneal scarring, trichiasis, need for/number of mucous membrane graft surgeries, and severity of symblephara.
Serial injection of 5-FU in the affected fornices is a promising treatment for severe vision-threatening conjunctival scarring from ocular cicatricial pemphigoid and Stevens–Johnson syndrome/toxic epidermal necrolysis. Given the excellent safety profile of 5-FU around the eye, the solid biologic foundation for using 5-FU in this setting, and the severe risk of vision loss from these disorders, the authors suggest that serial 5-FU injections be adopted as therapy for conjunctival scarring from ocular cicatricial pemphigoid or Stevens–Johnson syndrome/toxic epidermal necrolysis despite the limitations of this retrospective study.
Bui, Anh D.; Grob, Seanna R.; Tao, Jeremiah P.
To review the literature for the safety and efficacy of intralesional 5-fluorouracil (5-FU) in the management of oculofacial scars.
A literature search was performed in July 2019 in the PubMed database to identify reports of the use of 5-FU injections for modulating oculofacial cutaneous scars. The search yielded 152 articles, of which 15 met criteria outlined for assessment. Data were abstracted from these 15 relevant articles.
While there were no high-level prospective randomized controlled trials, 8 were lower-quality randomized controlled trial, 3 were retrospective cohort studies, and 4 were case series. Most studies pooled results of facial and nonfacial cutaneous applications. Three studies focused solely on oculofacial applications, and these were all lower-level evidence studies. The study outcomes included scar dimension reduction, erythema, patient satisfaction score, observer assessment of scar improvement, and recurrence rates. 5-Fluorouracil was administered as monotherapy or as part of multimodality treatment with other agents (usually corticosteroids) or with CO2 laser, radiotherapy, or pulsed dye laser. 5-Fluorouracil was usually given as an intralesional injection, but in some studies, it was applied topically after micropuncture of the skin. The number and timing of treatments varied between studies. Overall, the level of safety of 5-FU was high. Pain with injection was the most common reported side effect. Other common adverse side effects included pruritus, telangiectasias, changes in pigmentation, and purpura, and 2 studies noted more serious events, such as ulceration, superficial necrosis, and local infection. There were no severe side effects such as anaphylaxis, immune suppression, secondary malignancy, systemic infection, blindness, or death. In all studies, 5-FU was associated with prophylaxis of oculofacial scars or improvement of keloids or hypertrophic scars in terms of reducing size, erythema, and pruritus. 5-Fluorouracil application was associated with favorable patient satisfaction and observer assessment scores especially compared with corticosteroid injections alone.
High-quality randomized controlled trials are currently lacking, and the existing literature is predominately not specific to use of 5-FU on the face. These studies, however, suggest that intralesional 5-FU is safe and probably more effective than other options in the management of cutaneous scars in the oculofacial region. The delivery methods, timing, dosing, and concomitant therapies were highly variable. Further high-quality controlled studies specific to oculofacial scars may be indicated to assess the efficacy of 5-FU and to establish the best protocols for administering this medication.
Catherine J. Choi, Ann Q. Tran & David T. Tse
Purpose: To describe a novel technique of using a hard palate-dermis fat composite graft (HPDFG) for reconstruction of a contracted anophthalmic socket.
Methods: Retrospective, noncomparative, interventional case series of four patients who underwent HPDFG placement by one surgeon between 2010 and 2017.
Results: Six harvested HPDFGs were placed in four patients with contracted anophthalmic sockets. A harvested hard palate graft (HPG) and a dermis fat graft (DFG) were adjoined with sutures to form a composite graft. All adhesions and symblephara between the eyelid and the anterior surface of the anophthalmic socket were lysed. The HPG component was attached to the tarsal margin to vertically lengthen the eyelid. The free edge of the DFG was sutured to the cut edge of the bulbar conjunctiva to simultaneously expand the anterior conjunctival surface area and fornix volume. The line of union between the two grafts formed the apex of the new fornix. Four HPDFG were used to reconstruct both the upper and lower lid fornices in two severely contracted sockets. Three patients received post-operative 5-fluorouracil (5-FU) injections. Three patients underwent additional revisions with buccal mucous membrane graft, amniotic membrane graft, full-thickness skin graft, pedicle flap, and dermal fillers. All four patients achieved excellent cosmesis and comfortable prosthesis fit.
Conclusions: Composite HPDFG is an effective method of reconstructing a contracted anophthalmic socket by restoring volume, lengthening the posterior lamella, and expanding the fornix to allow for successful prosthesis retention. Adjunctive use of 5-FU injections can delay post-operative cicatrization.
Miltiadis Fiorentzis Periklis Katopodis Helen Kalirai Berthold Seitz Arne Viestenz Sarah E. Coupland
To investigate the cytotoxic effect of bleomycin, mitomycin C (MMC) and Fluorouracil (5‐FU) in combination with electroporation (EP) on human conjunctival melanoma (CM) and normal conjunctival cell lines using 2D and 3D cell culture systems in vitro.
Two CM (CRMM1, CRMM2) and one normal conjunctival epithelial cell line (HCjE‐Gi) were treated with various EP conditions and increasing concentrations of 5‐FU, MMC and bleomycin. Cell survival was assessed by MTT viability assay. All cell lines were seeded to create spheroids and were treated with bleomycin on day 3 and day 8 combined with EP. Spheroids were collected, fixed in buffered formalin and subsequently paraffin embedded for histological assessment of the effects of the treatment on cell viability.
CM cell lines were resistant to electroporation alone and showed a reduction in cell number only when treated with 1000 Volts/cm and 8 pulses. HCjE‐Gi cells showed higher sensitivity to electric pulses over 750 Volts/cm. MMC and 5‐FU demonstrated a higher cytotoxicity for the HCjE‐Gi cell line. The CM cell lines were resistant to MMC and 5‐FU. Bleomycin (1 μg/ml) alone had no significant effect on the HCjE‐Gi even when combined with EP conditions ≥750 Volts/cm. In contrast, it significantly (p ‐, paired t‐test) reduced cell viability in the CM cell lines. Spheroids treated with bleomycin and EP showed a reduction in tumour mass and proliferation rates after treatment.
Our in vitro study using 2D and 3D models indicates that the application of EP may effectively enhance chemotherapy with bleomycin in CM. This may offer new viable perspectives for CM treatment.
KE Hietanen, TA Järvinen, H Huhtala, TT Tolonen, HO Kuokkanen, IS Kaartinen
Keloids have high recurrence rates. Current first-line therapy is triamcinolone (TAC) injection, but it has been suggested that approximately 50% of keloids are steroid resistant. We compared the efficacy of intralesional 5-fluorouracil (5-FU) and triamcinalone injections in a double-blind randomized controlled trial. Forty-three patients with 50 keloid scars were treated with either intralesional TAC or 5-FU-injections over 6 months.
There was no statistically significant difference in the remission rate at 6 months between the 5-FU and TAC groups (46% vs 60%, respectively). Local adverse effects were higher in the TAC group compared to the 5-FU group. Occurrence of skin atrophy in TAC group was 44% and in the 5-FU group 8% (p < 0.05). Also the occurrence of telangiectasia in the TAC group was 50% and in the 5-FU 21% (p < 0.05). Vascularity of the keloids, assessed by spectral imaging and immunohistochemical staining for blood vessels, after treatment decreased in the TAC group, but not in the 5-FU group (p < 0.05). Fibroblast proliferation evaluated by Ki-67 staining significantly decreased in the TAC group (p < 0.05) but increased in the 5-FU group (p < 0.05).
TAC and 5-FU injections did not differ in their clinical effectivity in this randomized study, but 5-FU injections lead to increased proliferation rate and did not affect vascular density in histological assessment. Due to the greater number of adverse effects observed after TAC treatment, 5-FU injections may be preferable for cosmetically sensitive skin areas.
Lee, Bradford W.; Levitt, Alexandra E.; Erickson, Benjamin P.; Ko, Audrey C.; Nikpoor, Neda; Ezuddin, Nisreen; Lee, Wendy W.
Purpose: Cicatricial ectropion and periocular scarring can cause significant functional and cosmetic deficits. Surgical treatments can be associated with recicatrization, donor site morbidity, and textural and pigmentary abnormalities. This case series reports on efficacy and safety of a novel nonsurgical approach to treating cicatricial ectropion using ablative fractional laser resurfacing and laser-assisted delivery of 5-fluorouracil.
Methods: A retrospective review was conducted of all patients at a single institution who received ≥3 rounds of ablative fractional laser resurfacing with laser-assisted delivery of 5-fluorouracil. Six patients with cicatricial ectropion and periocular scarring secondary to reconstructive surgery, traumatic lacerations, and facial burns were included. Aesthetic and functional improvement were evaluated via fluorescein staining, tear breakup time, external photography, questionnaires gauging dry eye symptoms, and scar appearance.
Results: All patients showed functional improvement based on fluorescein staining (mean improvement 6.0 ± 1.4; p = 0.0007) and other indicators of dry eye. All 4 patients with lagophthalmos improved and 2 showed complete resolution. All patients demonstrated significant cosmetic improvement based on a validated scar assessment questionnaire (mean improvement 37.5 ± 18.9; p = 0.004), and 5 of 6 patients reported improved satisfaction with scar appearance (mean improvement 19.3 ± 12.8; p = 0.014). There were no adverse effects reported.
Conclusions: Ablative fractional laser resurfacing with laser-assisted delivery of 5-fluorouracil appears to be a safe and effective modality for treating the functional and aesthetic abnormalities associated with periocular scarring, yielding results that are difficult to attain through surgery alone. Optimal management of cicatricial ectropion and periocular scarring often requires multimodality treatment, and ablative fractional laser resurfacing with laser-assisted delivery of 5-fluorouracil may be considered as part of a comprehensive approach to managing periocular scars.
Sonal S Chaugule, Jennifer Park, Paul T Finger
Purpose: The purpose of this study is to report on the efficacy and safety of topical chemotherapy alone for giant ocular surface squamous neoplasia (OSSN). Methods: In this retrospective, interventional series, 10 eyes with giant OSSN underwent exfoliative biopsy to confirm the diagnosis followed by application of interferon alpha 2b (IFN α2b) and/or 5 fluorouracil, 1% (5FU). Reported outcome measures were tumor response, visual acuity, recurrence, systemic metastasis, and treatment complications. Results: Ten patients (3 female, 7 male) had a mean age of 73 (median, 69; range 40–89) years. Mean tumor diameter was 13.1 (median, 12.3; range 8.2–19.4) mm. Five (50%) eyes were treated with IFN-α2b alone; 1 (10%) with 5-FU alone and 4 (40%) required both IFN-α2b and 5-FU. The mean duration of treatment was 3, 0.5, and 6.4 months for IFN-α2b alone, 5-FU alone, and both IFN-α2b and 5-FU respectively. Complete tumor response was observed in all 10 cases at mean follow-up of 12.8 (median, 11.5; range, 3–25) months. Complications noted were transient irritation and burning (n = 4), dry eyes (n = 2), and transient flu-like symptoms (n = 2). There was no evidence of chemotherapy-related symblepharon, stem cell deficiency, scleral thinning, or corneal opacity. There were no tumor recurrences, and no patient required surgical excision or cryotherapy. Conclusion: Topical chemotherapy was a safe and effective treatment, inducing complete regression in all cases of giant OSSN in this series. There were no sight-limiting complications.