Use of saliva flow rate measurement in minor salivary glands autotransplantation for treatment of severe dry eye disease.

AIMS: To use minor salivary glands' flow rate (MSGFR) measurement in minor salivary glands (MSGs) autotransplantation for the treatment of severe dry eye disease (DED). METHODS: MSGs autotransplantations were performed in 18 eyes (17 patients) with severe DED. MSGFR were measured before operation. The upper or lower lip with higher MSGFR was selected as the donor site. Buccal mucosa was the back-up in cases labial MSGs showing markedly decreased MSGFRs. Two pieces of salivary lobules with the covering mucosa were harvested and transplanted to the recipient beds prepared in both upper and lower lids. RESULTS: The donor sites included lower lip in 12 eyes, upper lip in 5 eyes and buccal mucosa in 1 eye. Postoperative follow-up confirmed viable grafts in all cases. The overall subjective relief rate of DED symptoms was 58.8%, with Schirmer test values increasing from 0 mm to 4 mm (p<0.05). The mean preoperative MSGFR was 1.7 (range: 0.9-3.3) µL/min/cm2. ROC analysis indicated an outstanding discrimination power for preoperative MSGFR to predicate postoperative relief of DED symptoms (area under the curve (AUC)=0.948, p<0.01). The maximum sensitivity (100%) and specificity (72.7%) were reached at a cut-off of 1.785 µL/min/cm2. Patients with preoperative MSGFR >1.785 µL/min/cm2 showed greater improvement of Schirmer test values after surgery than those with MSGFR ≤1.785 µL/min/cm2 (p<0.05). CONCLUSION: MSGs transplantation proved to be useful for treating severe DED. The amount of postoperative lubrication and the treatment effect were positively correlated with preoperative MSGFR. MSGFR measurement and donor-site selection should be critical steps before the operation.

Minor salivary gland transplantation for severe dry eye disease due to cicatrising conjunctivitis: multicentre long-term outcomes of a modified technique.

AIM: To report the clinical outcomes of autologous minor salivary gland transplantation (MSGT) for the treatment of severe dry eye disease caused by cicatrising conjunctivitis. METHODS: This was a retrospective case series of patients undergoing MSGT at four different centres from 2016 to 2018. The technical modifications included en bloc harvesting of a 20 mm×15 mm mucosa-gland-muscle complex and fixation of the glands to the superior bulbar surface anchored to the superior rectus muscle. The primary outcome measure was improvement in best-corrected visual acuity (BCVA). Secondary outcome measures were change in Schirmer test scores and grades of conjunctival and corneal fluorescein staining, grades of corneal neovascularisation, opacification and keratinisation. RESULTS: 21 eyes of 19 patients underwent MSGT, with a median follow-up duration of 3 years. The median BCVA improved from a baseline value of 20/500 to 20/125 at 1 year (p=0.0004) and 20/80 at 3 years (p=0.0002) after surgery. The proportion of cases with BCVA ≥20/200 improved from 38% at baseline to 67% at 1 year (p=0.0294), 78% at 2 years (p=0.0227) and 93% at 3 years (p=0.0015) after surgery. There was a significant improvement (p<0.0036) in Schirmer scores, conjunctival and corneal staining scores as well as grades of corneal neovascularisation and opacification after surgery. There were no serious sight-threatening complications in the transplanted eyes or at the donor site. CONCLUSIONS: Long-term improvement in the visual acuity, ocular surface environment, and keratopathy was noted after MSGT performed in severely dry eyes using a modified technique.

Oral mucosa grafting in periorbital reconstruction.

To provide an extensive literature review on the clinical indications of oral mucosa grafts (OMG) and minor salivary gland grafts (MSGG) in periorbital reconstruction together with safe practice graft harvesting techniques to minimize donor-site morbidity. A literature review was performed by searching the databases of PUBMED, EMBASE, and COCHRANE library using the keywords: minor salivary glands; oral mucosal graft; orbit; and eye. The bibliographies of the pertinent articles were examined for additional papers. Indications for OMG include treatment of recurrent pterygia; socket contracture in anophthalmic patients; repair of eyelid deformities; ocular surface and fornix reconstruction following tumour resection, cicatricial ocular surface disorders, or chemical burns. More novel uses include repair of glaucoma aqueous drainage device erosions or leaking trabeculectomy blebs; scleral buckle exposure; and keratoprosthesis-related corneal melts as well as lining the dacryocystorhinostomy tract to prevent closure. Simultaneous MSGG transplantation may be used in the treatment of severe dry eyes or dry anophthalmic cavities. Harvesting from the inner cheek is preferred to lower lip as it causes less post-operative discomfort and neurosensory deficits. Suturing is recommended for smaller ovoid grafts as it allows less painful closure without tension, while larger rectangular defects are best left to heal by secondary intention. OMG and MSGG transplantation is a viable alternative to replace conjunctiva and restore the ocular surface. The donor site is readily accessible and widely available in most patients, grafting is fast and cheap, and the same site may undergo repeated harvesting with few donor site complications.

Therapeutic potential of human minor salivary gland epithelial progenitor cells in liver regeneration.

Liver disease is a serious problem affecting millions of people with continually increasing prevalence. Stem cell therapy has become a promising treatment for liver dysfunction. We previously reported on human minor salivary gland mesenchymal stem cells (hMSGMSCs), which are highly self-renewable with multi-potent differentiation capability. In this study, keratinocyte-like cells with self-regeneration and hepatic differentiation potential were isolated and characterized, and named human minor salivary gland epithelial progenitor cells (hMSG-EpiPCs). hMSG-EpiPCs were easily obtained via minor intraoral incision; they expressed epithelial progenitor/stem cell and other tissue stem cell markers such as CD29, CD49f, cytokeratins, ABCG2, PLET-1, salivary epithelial cell markers CD44 and CD166, and the Wnt target related gene LGR5 and LGR6. The cells were induced into functional hepatocytes in vitro which expressed liver-associated markers ALB, CYP3A4, AAT, and CK18. Upon transplantation in vivo, they ameliorated severe acute liver damage in SCID mice caused by carbon tetrachloride (CCl4) injection. In a two-thirds partial hepatectomy mouse model, the transplanted cells survived at least 4 weeks and exhibited hepatic potential. These findings demonstrate that hMSG-EpiPCs have potential as a cellular therapy basis for hepatic diseases, physiological and toxicology studies and regenerative medicine.

Minor Salivary Gland Transplantation for Severe Dry Eyes.

Dry eye is a multifactorial disease comprising a wide spectrum of ocular surface alterations and symptoms of discomfort. In most patients with aqueous-deficient dry eye, pharmaceutical tear substitutes are used to control symptoms and prevent ocular surface damage. However, in severe dry eye conditions caused by cicatricial disorders, such as Stevens-Johnson syndrome and ocular cicatricial mucous membrane pemphigoid, noninvasive treatments are insufficient, and patients are at risk of developing complications that can lead to blindness. The use of salivary glands as a source of lubrication to treat severe cases of dry eye has been proposed by different authors. The first reports proposed parotid or submandibular gland duct transplantation into the conjunctival fornix. However, complications limited the functional outcomes. Minor salivary gland autotransplantation together with labial mucosa has been used as a complex graft to the conjunctival fornix in severe dry eye with a good outcome. Our group demonstrated significant improvements in best-corrected visual acuity, Schirmer I test score, corneal transparency, and neovascularization after using this technique. A symptoms questionnaire applied to these patients revealed improvements in foreign body sensation, photophobia, and pain. Similar to tears, saliva has a complex final composition comprising electrolytes, immunoglobulins, proteins, enzymes, and mucins. We demonstrated the viability of minor salivary glands transplanted into the fornix of patients with dry eye by performing immunohistochemistry on graft biopsies with antibodies against lactoferrin, lysozyme, MUC1, and MUC16. The findings revealed the presence of functional salivary gland units, indicating local production of proteins, enzymes, and mucins.

Minor salivary glands and labial mucous membrane graft in the treatment of severe symblepharon and dry eye in patients with Stevens-Johnson syndrome.

OBJECTIVE: To evaluate minor salivary glands and labial mucous membrane graft in patients with severe symblepharon and dry eye secondary to Stevens-Johnson syndrome (SJS). METHODS: A prospective, non-comparative, interventional case series of 19 patients with severe symblepharon and dry eye secondary to SJS who underwent labial mucous membrane and minor salivary glands transplantation. A complete ophthalmic examination including the Schirmer I test was performed prior to and following surgery. All patients had a preoperative Schirmer I test value of zero. RESULTS: Nineteen patients with severe symblepharon and dry eye secondary to SJS were included in the study. There was a statistically significant improvement in the best spectacle-corrected visual acuity in eight patients (t test; p=0.0070). Values obtained in the Schirmer I test improved significantly in 14 eyes (73.7%) 6 months following surgery (χ(2) test; p=0.0094). A statistically significant increase in tear production (Schirmer I test) was found in eyes that received more than 10 glands per graft compared with eyes that received fewer glands (χ(2) test; p=0.0096). Corneal transparency improved significantly in 11 (72.2%) eyes and corneal neovascularisation improved significantly in five eyes (29.4%) (McNemar test; p=0.001 and p=0.0005). The symptoms questionnaire revealed improvement in foreign body sensation in 53.6% of the patients, in photophobia in 50.2% and in pain in 54.8% (Kruskal-Wallis test; p=0.0167). CONCLUSION: Labial mucous membrane and minor salivary glands transplantation were found to constitute a good option for the treatment of severe symblepharon and dry eye secondary to SJS. This may be considered as a step prior to limbal stem cell and corneal transplantation in these patients.

Tratamento das cavidades anoftálmicas secas com transplante de glândulas salivares labiais / Treatment of dry anophthalmic cavities with labial salivary glands transplantation

OBJETIVOS: Estudar os efeitos clínicos da secreção das glândulas salivares labiais na lubrificação das cavidades anoftálmicas secas, avaliar a durabilidade dos resultados e apresentar a técnica do transplante. A aplicação desse procedimento em cavidades anoftálmicas secas é inédita na literatura. MÉTODOS: Estudo prospectivo das cirurgias de enxertos glândulo-mucosos, compostos pela mucosa labial e glândulas salivares subjacentes, colocados no fórnice conjuntival de 5 pacientes com cavidades anoftálmicas que apresentavam grave xeroftalmia e retração dos fórnices conjuntivais. As cirurgias foram realizadas durante o período de julho/00 a janeiro/09. Dois pacientes já haviam sido tratados previamente com enxertos de mucosa ou de pele. A técnica do procedimento é descrita em detalhes. Os parâmetros que serviram para a análise comparativa dos resultados foram o quadro clínico, o aspecto do revestimento da cavidade, o ressecamento da superfície da prótese e a frequência do uso de colírios lubrificantes. RESULTADOS: Em todos os casos foi constatada a integração do enxerto e a melhora dos parâmetros avaliados. A evolução mostrou persistência e estabilidade dos resultados. CONCLUSÕES: A lubrificação da superfície da cavidade produzida pela secreção salivar mostrou ser eficiente, bem tolerada e constante, resultando maior conforto do uso da prótese. Infere-se que essa melhor lubrificação obtida ajuda a prevenir a evolução do processo de retração da cavidade. O transplante das glândulas salivares labiais para o fórnice conjuntival demonstrou ser um procedimento de fácil execução, acessível a qualquer cirurgião oftalmologista.

PURPOSE: To study the clinical effects of labial salivary glands' secretion used as ocular lubricant in anophthalmic cavities with severe xerophthalmia; to evaluate the evolution of the results; and to present the surgical technique. This procedure application in dry anophthalmic cavities is new in the literature. METHODS: Prospective study of patients presenting anophthalmic cavities with severe xerophthalmia and conjunctival fornix retraction treated with labial salivary glands transplantation to the conjunctival fornices. The surgeries were performed in five patients during the period of July 2000 to January 2009. In two cases the fornix retraction was previously treated with mucosa or skin graft. The surgical procedure technique is described in details. The postoperative comparative analysis was based on the clinical picture, the cavity surface aspect, the dryness of the cavity and prosthesis and the frequency of lubricant eye drops use. RESULTS: In all cases both graft integration and improvement of the evaluated parameters were observed. The evolution proved the persistence and stability of the results. CONCLUSION: The salivary secretion produced by the transplanted labial glands proved to be efficient as conjunctival lubricant, well tolerated and permanent, making the use of the prosthesis more comfortable. This improvement helps to prevent the progression of the cavity retraction process. Labial salivary glands graft into the anophtalmic cavity is a simple procedure and accessible to any ophthalmic surgeon.

Transplante de glândulas salivares menores no tratamento da ceratoconjuntivite seca em cães / Transplantation of the minor salivary gland in dogs with keratoconjunctivitis sicca

Relatou-se o efeito do transplante de glândulas salivares menores (TGSM) em cães portadores de ceratoconjuntivite seca (CCS) e estudaram-se os efeitos da secreção dessas glândulas usadas como alternativa de lubrificação ocular. A aplicação da técnica foi satisfatória, uma vez que resultou em melhora no quadro clínico oftalmológico sem que houvesse mínimas intercorrências pós-operatórias.

The effect of the transplant of minor salivary gland (TGSM) in carrying dogs of dry ceratoconjuntivite (CCS) and the effect of these used glands as alternative for ocular lubrication have been studied. The transplantation of the salivary gland in dogs with keratoconjunctivitis sicca (KCS) was reported and clinical effects of the salivary secretion as ocular lubricant for the relief of the disease were studied. Based on these results, it was concluded that the application of the TMSG technique in dogs with KCS is satisfactory, as demonstrated by improvement in the clinical ophthalmology and appreciated by the landlord regardin the results of the surgery and minimal postoperative complications.

[Treatment of dry anophthalmic cavities with labial salivary glands transplantation]. / Tratamento das cavidades anoftálmicas secas com transplante de glândulas salivares labiais.

PURPOSE: To study the clinical effects of labial salivary glands' secretion used as ocular lubricant in anophthalmic cavities with severe xerophthalmia; to evaluate the evolution of the results; and to present the surgical technique. This procedure application in dry anophthalmic cavities is new in the literature. METHODS: Prospective study of patients presenting anophthalmic cavities with severe xerophthalmia and conjunctival fornix retraction treated with labial salivary glands transplantation to the conjunctival fornices. The surgeries were performed in five patients during the period of July 2000 to January 2009. In two cases the fornix retraction was previously treated with mucosa or skin graft. The surgical procedure technique is described in details. The postoperative comparative analysis was based on the clinical picture, the cavity surface aspect, the dryness of the cavity and prosthesis and the frequency of lubricant eye drops use. RESULTS: In all cases both graft integration and improvement of the evaluated parameters were observed. The evolution proved the persistence and stability of the results. CONCLUSION: The salivary secretion produced by the transplanted labial glands proved to be efficient as conjunctival lubricant, well tolerated and permanent, making the use of the prosthesis more comfortable. This improvement helps to prevent the progression of the cavity retraction process. Labial salivary glands graft into the anophtalmic cavity is a simple procedure and accessible to any ophthalmic surgeon.

Autotransplantation of cryopreserved minor salivary glands: a new approach for management of radiation-induced xerostomia.

To date, it still is impossible to successfully prevent radiation-induced xerostomia. Therefore, further research, particularly regarding treatment, is urgently warranted. Lower labial mucosa with its submucosal minor salivary glands (MSGs) of approximately 2.5 x 3 cm can be prepared by means of a surgical knife or Ellman Surgitron high-frequency/low-temperature radiosurgical device. Also we can consider area of the palatine fovea to find and remove MSGs. We can find locations containing more MSGs via scintigraphy techniques and positron emission tomography. Removing of MSGs can be done 1-2 weeks before start of radiotherapy. Subsequently the MSGs containing complex graft should be cryopreserved via liquid nitrogen for long-term storage. Autotransplantation surgery will be carried out 2-3 months after radiotherapy. The frozen tissue could be thawed rapidly in a 37 degrees C water bath for 2-3 min. Host site should be as far as possible to the radiation zone and has a good blood supply. Hyperbaric oxygen therapy (30 treatment sessions before and 10 sessions after re-implantation) is strongly recommended. An aggressive short or medium-term antibiotic treatment will necessary to avoid infection. Immunosuppressive treatment will not require. The main criticism with this hypothesis is viability and usefulness of MSGs containing graft, after being frozen and subsequently thawed.

Minor salivary gland transplantation.

INTRODUCTION: Minor oral salivary glands exist in large numbers in the labial, buccal and palatal mucosa, and account for approximately half of the baseline secretion of saliva. They can be transplanted together with the overlying mucosa as a complex graft to the posterior lamella of the eyelids to increase ocular surface lubrication and reduce discomfort in dry eyes. MATERIAL AND METHODS: The surgical methods and the results of this technique in 17 patients are described. All patients had been retractive to medical treatment. The recipient bed over the lower or upper lid retractors and a donor tissue of lower labial mucosa with its submucosal minor salivary glands of approximately 2.5 x 2 cm were prepared by means of a surgical knife or Ellman Surgitron high-frequency/low-temperature radiosurgical device. The graft was cut in two strips of approximately 2.5 x 1 cm size and sutured to the recipient site with interrupted or running sutures. The labial wound was left open for second intention healing. RESULTS: All grafts remained viable and vascularised within 1 week. Vascularisation of the graft was associated with an improvement of symptoms and increased ocular surface lubrication. Complications included temporary labial hypaesthesia, partial necrosis of the graft (n = 1), herpes simplex virus keratitis (n = 1) and epiphora (n = 1). Viable glandular tissue was found in specimens taken 18 and 36 months postoperatively. Other reported complications include lid malpositioning such as ptosis and entropium. CONCLUSION: Transplantation of minor salivary glands is a promising new treatment option for severe dry eyes. The procedure is simple with minimal surgical risks. These grafts remain viable in over 90% and seem to be capable of sustaining a basal secretion for up to 36 months. Since experience with this technique is still very limited, prospective controlled studies have to be performed to establish the long-term survival of the glands and to characterise the salivary tear film and its impact on the ocular surface.

[Transplantation of labial salivary glands for severe dry eye treatment]. / Transplante de glândulas salivares labiais no tratamento do olho seco grave.

PURPOSE: To study the clinical effects of the secretion of transplanted labial glands used as ocular lubricant to treat severe dry-eye cases, to evaluate the duration of the results and to simplify the surgical technique. METHODS: Thirty-seven surgeries were performed in twenty-one patients during the period of July 2000 to January 2004. The graft, consisting of labial mucosa and underlying salivary glands, was transplanted to the previously prepared area in the conjunctival fornix. All procedures were recommended in severe dry-eye cases, that is, eyes with total or nearly total xerophthalmia. The preoperative and postoperative protocols are presented emphasizing the items which were used in the comparative analysis of the results as well as the technical description of the surgical procedure. RESULTS: The graft survival and integration into the host tissues were observed in 97.2% of the cases. The clinical improvement, demonstrated by the disappearance of the symptoms, better biomicroscopic aspect of the ocular surface, better vision and disuse of lubricant drops, was observed in 91.9% of the cases. The follow-up showed not only persistence but also stability of the results. Infection represented one case and ptosis represented three cases of the only four observed complications. CONCLUSION: The improvement of severe dry-eye cases detected after the transplantation of labial salivary glands is significant. It demonstrates that the lubricant ocular surface produced by the salivary secretion is efficient and well-tolerated. The follow-up shows that the result persists in the long term from which it is concluded that the production of the secretion is permanent. The surgical technique of transplanting the labial salivary gland to the conjunctival fornix is very simple and easily accessible to any ophthalmic surgeon.

Transplante de glândulas salivares labiais no tratamento do olho seco grave / Transplantation of labial salivary glands for severe dry eye treatment

OBJETIVO: Estudar os efeitos clínicos da secreção das glândulas labiais como alternativa de lubrificação ocular para alívio do olho seco, avaliar a durabilidade dos resultados e simplificar a técnica. MÉTODOS: Estudo prospectivo de 37 cirurgias de enxerto glândulo-mucoso, composto pela mucosa labial e glândulas salivares subjacentes, colocado no fórnice conjuntival de 21 pacientes. Todas as cirurgias foram realizadas em olhos com grave xeroftalmia, sendo a técnica do procedimento descrita em todos os detalhes. Os parâmetros que serviram para a análise comparativa dos resultados foram o quadro clínico, o brilho ocular, o quadro biomicroscópico, a visão e o uso de colírios lubrificantes. RESULTADOS: A integração do enxerto ocorreu em 97,2 por cento das cirurgias que foram realizadas durante o período de julho/2000 a janeiro/2004. Foi observado que em 91,9 por cento dos casos houve melhora dos parâmetros avaliados e a evolução (acompanhamento médio de 19,7 meses) mostrou persistência e estabilidade dos resultados. As complicações observadas foram: um olho com infecção hospitalar e três pálpebras com ptose. CONCLUSAO: A melhora clínica do olho seco grave observada após o enxerto das glândulas salivares labiais foi estatisticamente significativa. A lubrificação da superfície ocular produzida pela secreção salivar mostrou ser eficiente, bem tolerada e constante. O transplante das glândulas salivares labiais para o fórnice conjuntival demonstrou ser procedimento de fácil execução, acessível a qualquer cirurgião oftalmologista.

Surgical treatment of dry eye syndrome: conjunctival graft of the minor salivary gland.

Despite the availability of efficient tear substitutes, many patients with dry eye syndrome experience severe corneal injuries and a subsequent loss of vision. Surgical techniques using mayor salivary glands to provide a substitute for tears have been reported; with this technique the drainage of saliva goes into the conjunctival fornix, permitting corneal and conjunctival humidification. The authors describe a new surgical approach in which minor salivary glands are autotransplanted into the conjunctival fornix by means of a graft of the intraoral mucosa-transporting salivary glands. This approach was used in a 56-year-old woman with a 2-year history of refractory and pharmacologically untreatable dry eye syndrome caused by Sjögren's syndrome. The right eye had more severe corneal and conjunctival lesions than did the contralateral one, so the treatment was planned in the right eye only. A weekly follow-up during the first 6 months confirmed the significant improvement of dry eye symptoms in the surgically treated eye. Three months after surgery, a biopsy was performed in the minor salivary gland graft, and the histologic findings revealed the presence of glandular acinus, duct with mucin content, and lymphocyte infiltration. The significant improvement obtained in this patient suggests that the secretion from the grafted salivary minor glands was better in promoting homeostasis of the ocular surface than are artificial tears. This may be explained by: (1) The lacrimal and salivary secretions contain biologically active constituents that may protect from infection and promote normal growth epithelium; (2) The secreted mucin is thought to coat the epithelial surface, reducing the high surface tension of the eye wetted by aqueous tears; (3) The thick secretions of the minor gland might act in reducing the evaporation of the underlying tear layer and form a hydrophobic barrier along the lid margin that can retain the lid margin tear string and prevent its flow onto the skin. Minor gland salivary autotransplant is a new surgical technique with effectiveness demonstrated in one patient, but the scientific explanation is not clear; additional experience with more cases could confirm the initial success.