Long-term outcome of cultivated oral mucosal epithelial transplantation for fornix reconstruction in chronic cicatrising diseases.

BACKGROUND/AIMS: To investigate the long-term outcomes of cultivated oral mucosal epithelial transplantation (COMET) for fornix reconstruction in eyes with chronic cicatrising disease. METHODS: This retrospective cohort study involved 16 eyes of 15 patients who underwent COMET for symblepharon release and fornix reconstruction between June 2002 and December 2008. The mean postoperative follow-up period was 102.1±46.0 months (range: 32-183 months). The treated cicatrising disorders included ocular cicatricial pemphigoid (OCP, five eyes), thermal/chemical injury (three eyes) and other chronic diseases (seven eyes; including recurrent pterygium (two eyes), Stevens-Johnson syndrome (one eye) and graft-versus-host disease (one eye)). Ocular-surface appearance was evaluated before surgery, at 1, 4, 12 and 24 weeks postoperative, and then annually based on the previously reported scoring system. Main outcome measures included overall and disease-specific fornix-reconstruction success probabilities analysed by the Kaplan-Meier survival curve. Symblepharon/fornix-shortening recurrence at 24 weeks postoperative, and its relationship to long-term surgical success was also examined. RESULTS: At 5 years postoperative, the mean±SD overall fornix-reconstruction success probability was 79.6%±10.7%, and success probability for thermal/chemical injury and OCP was 100% and 53.3%±24.8%, respectively (p=0.53, log-rank test). The 3-year success probability was significantly higher in the no-disease-recurrence group at 24 weeks postoperative (13 eyes) than in the disease-recurrence group (three eyes) (100% and 33.3%±27.2%, respectively) (p=0.0073, log-rank test). CONCLUSION: COMET was found to be safe and effective for symblepharon release and long-term fornix reconstruction in eyes with chronic cicatrisation. Although the 5-year success probability differed depend on the underlying disease, ocular-surface appearance at 24 weeks postoperative is a factor for predicting long-term outcome.

Transmucosal Boston Keratoprosthesis Type I in a Patient With Advanced Ocular Cicatricial Pemphigoid.

PURPOSE: To describe a novel surgical technique using the Boston Keratoprosthesis (KPro) type I in a patient with advanced ocular cicatricial pemphigoid (OCP) using oral mucosa for covering the prosthesis. METHODS: We present the case of an 85-year-old man previously diagnosed with type 2 diabetes and advanced OCP nonresponsive to immunosuppressive treatment, whose best-corrected visual acuity was light perception and projection in both eyes. After examination, Boston KPro type I in the right eye was contemplated because osteo-odonto KPro and Tibial bone KPro were not feasible because of the patient's osteoporosis and edentulism. Reconstruction of the ocular surface was first performed using oral mucosa to release the symblepharon and try to deep the fornices. Three months later, the oral mucosa was lifted, and the Boston KPro type I was implanted using the patient's own cornea. Then, a modification of the standard surgical technique was carried out, replacing the use of contact lens for covering the prosthesis with an oral mucosa graft with a central trephination as an alternative option in fornix foreshortening cases. RESULTS: After 11 months, visual acuity was stable to 0.2 decimal. No postoperative complications have been encountered, and prosthesis was in place. CONCLUSIONS: The surgical technique of transmucosal Boston KPro type I may be considered a surgical alternative in patients with advanced OCP who present with severe fornix foreshortening, where osteo-odonto KPro or Tibial bone KPro cannot be performed due to osteoporosis or edentulism or when the Boston KPro type II is not readily available.

Bilateral keratoprostheses in a patient with ocular mucous membrane pemphigoid.

Mucous membrane pemphigoid (MMP) with ocular involvement, also referred to as ocular cicatricial pemphigoid, is a rare, autoimmune blistering disease that can have devastating effects for patients. The resulting corneal neovascularization, recurrent corneal abrasions, and ulceration can ultimately result in severe vision loss. We present a 64-year-old man with recalcitrant ocular MMP and consequently advanced corneal involvement that received bilateral keratoprostheses. This case highlights an aggressive but successful placement of bilateral keratoprostheses in recalcitrant ocular MMP, which restored his vision and ultimately his quality of life.

Prospective Clinical Trial of Corneal Reconstruction With Biomaterial-Free Cultured Oral Mucosal Epithelial Cell Sheets.

PURPOSE: To investigate the efficacy and safety of transplantation with biomaterial-free cultured oral mucosal epithelial cell sheets (COMECs) for ocular reconstruction in subjects with total limbal stem cell deficiency. METHODS: A prospective clinical trial (NCT02149732) was conducted in 8 subjects with total limbal stem cell deficiency after approval from the institutional review board of Seoul National University Hospital (H-0707-043-213) and the Ministry of Food and Drug Safety of Korea. COMECs were prepared in a culture system without the use of any temperature-sensitive polymers or carriers. The COMECs were transplanted without suture fixation. Four subjects underwent penetrating keratoplasty after stabilization of the COMEC transplant. Stable epithelialization, changes in visual acuity, and postoperative complications were evaluated for 6 months. Corneal cytokeratins (K) of 4 subjects who underwent penetrating keratoplasty were stained with an immunofluorescent agent. RESULTS: The ocular surface was successfully reconstructed in 6 eyes. Complete stable epithelialization was achieved within a mean of 53.6 days. Visual improvement (≥2 lines) was achieved in 62.5% of the eyes. K12 (corneal phenotype), K4, and K13 (mucosal phenotype) were well expressed in grafts after keratoplasty, whereas K1, K8, and K19 were barely expressed. No ocular infections, local tumor formation, or remarkable systemic complications were observed. Ocular reconstruction using COMECs failed in 2 eyes, which had full symblepharon in 4 quadrants. CONCLUSIONS: Transplanting biomaterial-free COMECs seems to be an efficient and safe procedure to reconstruct the ocular surface in patients who are completely limbal stem cell deficient without a full symblepharon.

Reconstructive subperiosteal midface lift: A three nonvisible incision approach.

This article describes our surgical technique for subperiosteal midface elevation in patients with paralytic lower eyelid malposition or cicatricial inferior eyelid retraction. Nineteen patients with paralytic lower eyelid malposition and 15 patients with cicatricial inferior eyelid retraction underwent a subperiosteal midface lift (n = 34). The procedure was performed under local anesthesia through three nonvisible incisions. A transconjunctival incision allows preseptal dissection to the orbital rim, followed by a subperiosteal dissection of the midface. An oral incision is useful to achieve complete subperiosteal dissection and to perform the distal periostomy, which allows complete release of the midface soft tissues. A temporal incision provides access to the temporal fascia for fixation of the elevated tissues and gives the surgeon the possibility of removing redundant skin from the scalp instead of the lower eyelid. Additional posterior lamellar grafting was performed in 24 patients. There was a statistically significant reduction in the distance from the pupil centre to the lower eyelid (margin reflex distance, MRD2) 1 month after surgery (preoperative MRD2 9.62 ± 4.52 mm, postoperative MRD2 5.28 ± 2.62 mm). The ectropion and lower eyelid retraction was resolved in all patients, except for one recurrence. Midfacial elevation is a safe and effective surgical technique in the treatment of static lower eyelid malposition after chronic facial nerve palsy or posttraumatic or iatrogenic lower eyelid retraction.

Mucous Membrane Pemphigoid Causing Central Airway Obstruction.

Mucous membrane pemphigoid (MMP) is a rare variant of the skin disease pemphigoid, which predominantly involves the mucous membranes. This rare autoimmune disease that infrequently affects the respiratory tract is characterized by subepithelial blister formation that may result in scarring. Immunopathologic examination of mucous membranes reveals the deposition of immunoglobulins and complement within the subepithelial basement membrane. We describe a patient with undiagnosed MMP, with a near-fatal presentation of central airway obstruction causing acute respiratory distress. The patient was successfully treated with emergent rigid bronchoscopic resection of a ball valve-like endotracheal mass, and diagnosed with a rare variant of pemphigoid disease, MMP. The patient was treated with mycophenolate and was clinically in remission, with bronchoscopically stable lesions at 1 year of follow-up.

Endoscopic Cyclophotocoagulation for the Treatment of Glaucoma in Boston Keratoprosthesis Type II Patient.

We describe the surgical technique of endoscopic cyclophotocoagulation in a Boston keratoprosthesis type II patient. This patient with ocular cicatricial pemphigoid had pars plana endoscopic cyclophotocoagula through wounds created in the eyelids.

[Lesions of the oral mucosa : Differential diagnostic approach from the maxillofacial surgeon's perspective]. / Schleimhauterkrankungen : Differenzialdiagnostischer Zugang aus kieferchirurgischer Sicht.

A detailed medical history and a careful clinical examination are the basis for developing a list of possible differential diagnoses in lesions of the oral mucosa. On this basis, it can be decided whether a lesion can be observed for 14 days after removal of possible causes or the start of a trial treatment, or whether a biopsy for histological examination must be taken immediately. An excisional biopsy is performed for small and presumably benign lesions, an incisional biopsy for large and presumably malignant lesions. If an autoimmune blistering disease is suspected, a second sample for examination by immunofluorescence is taken. Depending on the results of the histological examination further treatment steps are planned or regular appointments for follow-up are arranged.

[Anti-p200/anti-laminin γ1 pemphigoid and BP180 NC16A/4575- positive mucous membrane pemphigoid : late diagnosis in a patient with disease-related loss of vision and multiple previous surgical interventions]. / Anti-p200/Laminin-γ1-Pemphigoid in Kombination mit einem BP180 NC16A/4575-positiven Schleimhautpemphigoid : Späte Diagnosestellung bei krankheitsbedingter Amaurosis und mehrfachen Voroperationen.

A 87-year-old woman presented with a three-year history of partially erosive, partially bullous skin and mucosal lesions, symblepharon of both eyelids as well as dysphagia. To date, multiple excisions of the skin lesions, which had been described as "skin tumors" by surgeons, had been performed. The synopsis of histology, direct and indirect immunofluorescence established the diagnosis of anti-p200/anti-laminin γ1 pemphigoid and BP180 NC16A/4575- positive mucous membrane pemphigoid with an unusual "epitope-spreading" phenomenon. Due to the late initiation of therapy, the disease-related loss of vision unfortunately was irreversible.

Cultivated oral mucosal epithelial transplantation for persistent epithelial defect in severe ocular surface diseases with acute inflammatory activity.

PURPOSE: To assess the clinical efficacy of cultivated oral mucosal epithelial transplantation (COMET) for the treatment of persistent epithelial defect (PED). METHODS: We treated 10 eyes of nine patients with PED (Stevens-Johnson syndrome: three eyes; thermal/chemical injury: five eyes; ocular cicatricial pemphigoid: two eyes) with COMET at Kyoto Prefectural University of Medicine, Kyoto, Japan from 2002 to 2008. RESULTS: Preoperatively, PED existed on over more than 50% of the corneal surface in seven eyes. Severe ocular surface inflammation with fibrovascular tissue surrounded the PED in all 10 eyes. At 24-weeks postoperative, PED had improved in all cases except 1 in which the patient was unable to return to the hospital (95% CI, 55.5-99.7; Wilcoxon signed-rank test, p = 0.0078). The preoperative median of logarithmic minimum angle of resolution was 1.85 (range 0.15-2.70), and 1.85, 1.85, and 1.52 at the 4th, 12th, and 24th postoperative week, respectively. The mean total preoperative ocular surface grading score was 7.0 (range 4-17). At 4 and 12 weeks postoperative, the total ocular surface grading score had improved significantly (p = 0.0020, p = 0.0078), and at 24 weeks postoperative, it was 3.0 (range 2-12, p = 0.0234). During the follow-up period (median 23.3 months, range 5.6-39.7 months), no recurrence of PED was observed in any eye, and long-term ocular surface stability was obtained. CONCLUSION: COMET enabled complete epithelialization of PED and stabilization of the ocular surface in patients with severe ocular surface disease, thus preventing end-stage cicatrization and vision loss at a later stage.

Outcomes of cataract surgery in ocular cicatricial pemphigoid.

PURPOSE: To report the outcomes of cataract surgery in ocular cicatricial pemphigoid (OCP). SETTING: L. V. Prasad Eye Institute, Hyderabad, India. DESIGN: Retrospective, interventional case series. METHODS: Patients diagnosed with OCP who had undergone cataract surgery were included. Staging of disease, type of surgery, pre- and postoperative best-corrected visual acuity (BCVA), and number and duration of topical and systemic medications were recorded. Complications and any exacerbation or worsening of disease were noted. RESULTS: Nine eyes of 7 patients (3 male, 4 female) were included in the study, with mean age of 60.44 ± 2.6 years (range 56-64 years). Follow-up ranged from 6 months to 10 years (mean 52.9 ± 46.25 months). Surgery performed was extracapsular cataract extraction with posterior chamber intraocular lens implantation (n = 5) or phacoemulsification with posterior chamber intraocular lens implantation (n = 4). Best-corrected visual acuity improved by more than 2 lines in 6 of 9 (66.67%) eyes, which remained stable till the last follow-up. Three eyes had no visual improvement due to corneal scar in 2 patients and preexisting posterior staphyloma in 1 eye. Disease progression was noted in 2 of 9 operated eyes by one stage at the end of 1 year. CONCLUSION: In this series, cataract surgery could be safely performed with no major intra- or postoperative complications. While the surgical intervention itself was not associated with acute exacerbations of inflammation, progression of disease was noted in some cases over time. In spite of ongoing disease, cataract surgery in OCP was associated with stable visual outcomes.

The Boston keratoprosthesis type I in mucous membrane pemphigoid.

PURPOSE: To evaluate the use of the Boston keratoprosthesis type I implantation in patients with mucous membrane pemphigoid (MMP). METHODS: Retrospective review of 8 eyes of 8 patients with severe ocular surface disease and corneal blindness as a result of MMP who underwent Boston keratoprosthesis type I implantation at the Massachusetts Eye and Ear Infirmary from January 1, 2000, through December 31, 2009. The main outcome measures were best-corrected visual acuity, keratoprosthesis retention, and postoperative complications. RESULTS: The mean age of patients was 71.3 years (range, 55-94 years), and the mean duration of their disease preoperatively was 6.1 years (range, 1.7-11.4 years). Visual acuity after the surgery improved to 20/200 or better in 6 eyes (75%) and to 20/40 or better in 3 eyes (37.5%). Only 1 of 6 eyes (16.7%) was able to maintain visual acuity of 20/200 or better over a mean follow-up period of 3.2 years. Five of the 8 Boston keratoprosthesis type I devices (62.5%) extruded or had to be replaced during a mean follow-up time of 1.7 ± 1.7 years. Loss of vision to worse than 20/200 during the follow-up period occurred because of keratoprosthesis type I extrusion, end-stage glaucoma, and retinal or choroidal detachment. CONCLUSIONS: The clinical outcomes of Boston keratoprosthesis type I implantation in MMP are guarded and, as judged from the literature, less favorable than those with the Boston keratoprosthesis type II for the same disease.

Long-term outcomes of MICOF keratoprosthesis in the end stage of autoimmune dry eyes: an experience in China.

AIMS: To evaluate the clinical outcomes following Moscow Eye Microsurgery Complex in Russia keratoprosthesis (MICOF KPro) implantation in end-stage autoimmune dry eyes. METHODS: A retrospective observational case series. Fourteen patients with end-stage autoimmune dry eyes underwent MICOF KPro surgery by one surgeon (YH) in the Chinese PLA General Hospital between 2000 and 2009. Retention of the prosthesis and vision were recorded and postoperative complications were analysed. RESULTS: Preoperative diagnosis included Stevens-Johnson syndrome (n=7), ocular cicatricial pemphigoid (n=4) and Sjogren's syndrome (n=3). The mean follow-up period was 3.9 years (range 10 months-7.8 years). After surgery, 13 eyes (93%) showed a visual acuity of 20/200 or better and 6 eyes (43%) achieved excellent vision of 20/40 or better. At last visit, 69% of the eyes (9/13) maintained a visual acuity of at least 20/200. The first case retained a visual acuity of 20/80 7.8 years after the operation. The most common complication was stromal melting that threatened anatomical success. Seven of the first eight patients showed tissue melting, and four of them had leakage. All of these were repaired successfully. The latter six cases received prophylactic autologous auricular cartilage implantation to reinforce the anterior surface of recipient's cornea at either stage 1 or 2. Other causes of vision loss included pre-existing glaucoma (n=6), sterile vitritis (n=5), cylinder loosening (n=1) and retroprosthetic membrane (n=4). CONCLUSION: MICOF KPro provided useful vision for the end stage of autoimmune dry eyes in our study. Anatomical stability of KPro was achieved in all cases using repair and reinforcing surgery.

[Amniotic membrane in conjunctivoplasty]. / Membrana amniotica în conjunctivoplastie.

The basic principles of conjunctival reconstruction are similar in all pathologies that inflict conjunctival tissue loss. Large conjunctival defects are difficult to treat, with little conjunctival reserve that can be used to close the defect. The study had the objective to find alternatives to conjunctival autograft. Frozen amniotic membrane was investigated. From 27 cases, 22 cases were reconstructed using amniotic membrane alone, but in 5 cases conjunctival autograft was also needed. Bulbar conjunctiva was reconstructed in 23 cases, of which 19 with pterygium, 3 with conjunctival tumors, one operatory plague. Fornix reconstruction was carried out in 4 cases, one tumor and 3 symblepharons (2 after conjunctival burns and one pemfigus). The rate of pterygium recurrence was 7,14%. Amniotic membrane can heal large defects of the conjunctiva, either bulbar or forniceal.

Oral mucosal graft to correct lid margin pathologic features in cicatricial ocular surface diseases.

PURPOSE: To evaluate the efficacy of oral mucosal graft to correct not only lid margin keratinization and trichiasis or distichiasis, but also incomplete closure in severe cicatricial ocular surface diseases. DESIGN: Retrospective, noncomparative, interventional case series. METHODS: Twenty-two eyes (39 eyelids) of 19 patients received an oral mucosal graft during lid margin reconstruction from September 2007 through February 2010. Relief of symptoms, conjunctival inflammation, corneal epithelial abnormalities, and visual acuity were compared before and after surgeries as outcome measures. RESULTS: Among 22 eyes, 10 eyes (45.5%) had lid margin keratinization, trichiasis or distichiasis, or both, resulting in blink-related microtrauma. The oral mucosal graft resulted in successful correction in 6 eyes; in the remaining eyes, trichiasis in 3 eyes and distichiasis in 1 eye were away from the corneal surface. Incomplete closure present in 12 (54.5%) eyes was completely corrected in 9 eyes and was much improved in the remaining 3 eyes. During a mean follow-up of 16.2 months, reports of foreign body sensation, photophobia, pain, burning, tearing, and discharge were relieved significantly in 17 (77.3%) of 22 eyes. The visual acuity was improved in 13 eyes (59.1%) and was maintained in 8 eyes. Conjunctival inflammation was reduced markedly in 19 eyes (86.4%). Corneal epithelial defect and superficial punctate keratopathy were healed rapidly or improved in 14 eyes, and regression of superficial vascularization was noted in 1 eye. CONCLUSIONS: Oral mucosal graft can reduce not only blink-related microtrauma caused by lid margin keratinization and trichiasis or distichiasis, but also exposure caused by cicatricially induced incomplete closure, thus preventing further deterioration of the ocular surface.

The relationship between preoperative clinical scores and immunohistological evaluation of surgically resected tissues in chronic severe ocular surface diseases.

PURPOSE: To clarify the relationship between clinical symptoms and histological status in patients with ocular cicatricial pemphigoid (OCP) and Stevens-Johnson syndrome (SJS). METHODS: Clinical symptoms of four OCP and eight SJS patients in the chronic phase were scored with our recently proposed grading system. The histological status of the pannus tissue removed from the corneal surface during surgery was investigated using immunohistological techniques. RESULTS: All participants showed total loss of the palisades of Vogt and conjunctivalization of the entire corneal surface. All pannus tissues expressed the conjunctival epithelium marker CK4/13. The pannus tissue in clinically keratinized SJS expressed skin epidermal major cytokeratins, but the tissues of nonkeratinized SJS did not. CONCLUSIONS: Clinical observation and the use of our recently proposed grading system agreed with the immunohistological status with respect to keratinization, cell proliferation, and corneal/conjunctival cell typing. These findings facilitate our understanding of the pathogenesis of OCP and SJS, and will hopefully contribute to the development of future treatment strategies and improve predictions of the postoperative prognosis of ocular surface reconstruction in patients with OCP and SJS.

Laryngeal mucous membrane pemphigoid: a systematic review and pooled-data analysis.

OBJECTIVES/HYPOTHESIS: To perform a systematic pooled-data analysis of literature data involving laryngeal mucous membrane pemphigoid (MMP). STUDY DESIGN: A systematic review and pooled-data analysis. METHODS: We conducted a systematic literature search of MEDLINE, EMBASE, Cochrane Central Register of Clinical Trials, Cochrane Database of Systematic Reviews, clinicaltrials.gov, and the National Guideline Clearinghouse databases without language restriction for studies including combinations of relevant terms. All authors independently screened the abstracts of the search results, identified articles eligible for review, and critically appraised the full-text studies. Pooled-data analyses and Kaplan-Meier survival analyses were conducted using SPSS version 16.0 software (SPSS Inc., Chicago, IL). RESULTS: Of the 2,524 citations reviewed, the included articles consisted of 63 case reports and 10 case series reporting on 141 patients with laryngeal MMP. No clinical trials or comparative trials were found. The overall calculated prevalence of laryngeal MMP was 12.2% (95% confidence interval [CI], 11.5-12.9%) of cases of MMP or one in 10 million persons in the general population. Mean age at laryngeal MMP onset was 59.7 years (95% CI, 57.9-61.1 years), and the supraglottis was the most commonly affected site (84.8%, 95% CI, 82.5-87.2%). Distribution among genders was equivalent (P = .655). The presence of antiepiligrin autoantibodies was associated with increased laryngeal involvement (Odds ratio 7.9, 95% CI, 3.9-16.0). The overall 5-year relative survival rate was 92.4% (standard error, 8.4) with a follow-up range of 1 to 221 months. Standard medical therapy alone occasionally improved the condition; however, relapses were frequent, and 10.5% eventually required tracheostomy. Laryngeal surgical interventions seemed to be effective in severe cases. CONCLUSIONS: Laryngeal MMP is a rare condition that can be life threatening without proper treatment and frequent follow-up.