Periocular Mass Due to Persistent Secretion Within a Transplanted Parotid Duct.

A male patient underwent microvascular transplantation of an autologous submandibular gland and its associated (Wharton's) duct for management of very severe right keratoconjunctivitis sicca due to Stevens-Johnson syndrome; due to hypersecretion, the gland was later removed in toto. Twenty-two years later, he presented with a nontender, sausage-like mass lying subcutaneously in the right temple. Intraoperatively a fluctuant tubular mass passing from the temporalis fossa to the superotemporal conjunctiva was identified and excised intact. Histology showed a slightly proteinaceous fluid within a duct lined with cuboidal epithelium, this being compatible with Wharton's duct. This case highlights that iatrogenic causes should be considered with any history of periocular injury or surgery.

Changes in tear production in a dog with keratoconjunctivitis sicca for a year after inevitable nictitating membrane gland resection due to suspicion of a malignant tumour.

Since the removal of the NM causes KCS in dogs, it was contraindicated to remove the NM unless unavoidable such as in a malignant tumour. However, to the best of author's knowledge, there are no reports of conjunctivitis and keratitis owing to decreased tear production following removal of the NM gland. This case study demonstrates the tear production changes in a dog for a year after removal of the nictitating membrane (NM) due to suspicion of a malignant tumour. A 13-year-old spayed female English Cocker Spaniel who had suffered from severe ocular discharge, discomfort, keratoconjunctivitis sicca (KCS), and NM enlargement in the right eye was brought to our hospital. The dog could not tolerate treatment with topical 0.2% cyclosporine or corticosteroids. The dog's right eye had NM gland prolapse, severe follicular conjunctivitis and a very low Schirmer tear test-1 (STT-1) value of 3 mm/min. Furthermore, the result of fine needle aspiration of the enlarged NM gland suggested a risk of malignancy. Despite the risk of KCS, complete NM resection was performed to diagnose the tumour. Fortunately, the final histopathological evaluation revealed chronic inflammation without any evidence of malignancy. Contrary to concerns that the STT-1 value would further decrease after the removal of the NM gland, the STT-1 value remained elevated compared to that before surgery, and the clinical symptoms improved for a year. It is generally known that NM gland resection is not recommended due to the risk of developing iatrogenic KCS unless a malignant tumour is suspected. In this case, surgical removal of the inflammatory NM gland that was not responsive to medications had a positive effect on KCS. Since the inflammatory and structural disease of the NM was strengthening KCS, the outcome was thought to be different from that when the normal third eyelid was removed.

Factors influencing the long-term results of autologous microvascular submandibular gland transplantation for severe dry eye disease.

We assessed long-term outcomes of autologous microvascular submandibular gland (SMG) transplantation for severe dry eye disease and investigated factors influencing long-term results. From August 1999 to January 2015, 185 patients (200 eyes) with severe dry eye received SMG transplantation. Subjective assessments and ophthalmologic evaluations were performed before and after transplantation. Follow-up results showed successful transplantation in 180 of 200 eyes (success rate: 90%), resulting in marked symptomatic relief of xerophthalmia. Surgery failed due to vascular thrombosis (15 glands) and duct obstruction (5 glands). Follow-up data were available for 163 eyes. Epiphora occurred in 98 (60.1%) eyes and was effectively managed by surgical reduction of graft, topical atropine gel and botulinum toxin injection. Wharton's duct obstruction occurred in 16 (10.6%) eyes and was treated by duct reconstruction. Subjective satisfaction was achieved in 143 (87.7%) eyes. Mean score of fluorescent staining reduced from 11.25±1.42 to 7.25±3.37. Postoperative best-corrected visual acuity improved in 85 (56.3%) eyes. Our clinical experience proved that SMG transplantation is effective and grants long-term improvement in severe dry eye. Secretory function of transplanted SMGs remains active and stable. Blood vessel thrombosis, Wharton's duct obstruction, and epiphora are primary factors influencing results.

Microvascular Submandibular Gland Transplantation for Severe Keratoconjunctivitis Sicca: A Single-Institution Experience of 61 Grafts.

PURPOSE: Keratoconjunctivitis sicca (KCS) is a relatively common disease that results in discomfort, tear film instability, visual impairment, and ocular surface damage. Artificial tear substitutes may be suitable for the treatment of mild KCS, but no effective treatment currently exists for severe KCS. Therefore, this study evaluated the effectiveness of autologous microvascular submandibular gland transplantation in the treatment of severe KCS. PATIENTS AND METHODS: A total of 61 eyes (56 patients) with severe KCS were treated with autologous submandibular gland transplantation from June 2002 to June 2017. The cephalic vein or the great saphenous vein was applied to solve the problem of unmatched veins. RESULTS: In 53 cases (53 of 56, 94.6%), 58 glands (58 of 61, 95.1%) were transplanted successfully. The mean Schirmer I test value improved from 0.78 ± 0.84 mm preoperatively to 18.83 ± 5.72 mm in the stable period after transplantation. Epiphora (14 of 58, 24.14%) was the most common complication of this procedure. Other postoperative complications included venous thrombosis (6 of 61, 9.84%), local infection (2 of 58, 3.45%), xerostomia (2 of 53, 3.77%), duct fistula (1 of 58, 1.72%), sialolithiasis (1 of 58, 1.72%), and ranula (1 of 58, 1.72%). CONCLUSIONS: Autologous microvascular submandibular gland transplantation is a credible and effective solution for severe KCS.

Autonomic reinnervation and functional regeneration in autologous transplanted submandibular glands in patients with severe keratoconjunctivitis sicca.

Autologous submandibular gland (SMG) transplantation has been proved to ameliorate the discomforts in patients with severe keratoconjunctivitis sicca. The transplanted glands underwent a hypofunctional period and then restored secretion spontaneously. This study aims to investigate whether autonomic nerves reinnervate the grafts and contribute to the functional recovery, and further determine the origin of these nerves. Parts of the transplanted SMGs were collected from the epiphora patients, and a rabbit SMG transplantation model was established to fulfill the serial observation on the transplanted glands with time. The results showed that autonomic nerves distributed in the transplanted SMGs and parasympathetic ganglionic cells were observed in the stroma of the glands. Low-dense and unevenly distributed cholinergic axons, severe acinar atrophy and fibrosis were visible in the patients' glands 4-6 months post-transplantation, whereas the cholinergic axon density and acinar area were increased with time. The acinar area or the secretory flow rate of the transplanted glands was statistically correlated with the cholinergic axon density in the rabbit model, respectively. Meanwhile, large cholinergic nerve trunks were found to locate in the temporal fascia lower to the gland, and sympathetic plexus concomitant with the arteries was observed both in the adjacent fascia and in the stroma of the glands. In summary, the transplanted SMGs are reinnervated by autonomic nerves and the cholinergic nerves play a role in the morphological and functional restoration of the glands. Moreover, these autonomic nerves might originate from the auriculotemporal nerve and the sympathetic plexus around the supplying arteries.

Canine oral mucosa evaluation as a potential autograft tissue for the treatment of unresponsive keratoconjunctivitis sicca.

PURPOSE: Labial mucosa transplantation for the treatment of canine keratoconjunctivitis sicca (KCS) has been reported recently. Postoperative alleviation of clinical signs was noted and assumed to be the result of labial salivary glands providing lubrication to the ocular tissue. The aim of this study was to evaluate the presence of minor salivary glands (MSG) in the canine oral mucosa. METHODS: Oral mucosal biopsies were collected from six dogs that died (n = 1) or were euthanized (n = 5) for reasons unrelated to this study. The breeds included were two Doberman Pinschers, one Labrador Retriever, one Portuguese Water Dog, one German Shepherd Dog, and one mixed canine. Three were spayed females, and three were castrated males with the median age of 9 years (range, 6-13 years). Samples were obtained by an 8-mm punch biopsy at the following locations of the canine oral cavity: upper rostral labial mucosa at midline, lower rostral labial mucosa at midline, upper labial mucosa near the commissure, lower labial mucosa near the commissure, and buccal mucosa approximately 1 cm caudal to the commissure. Samples were routinely processed with hematoxylin and eosin, and periodic acid-Schiff stains. Samples were evaluated by light microscopy. RESULTS: At the selected locations, no MSG or other secreting cells were detected. CONCLUSIONS: Minor salivary glands are not associated with alleviation of canine KCS symptoms following labial mucosa transplantation. Further studies are needed to determine the mechanism leading to the transient improvement of KCS symptoms in canine patients following labial mucosa transplantation.

Boston Type I Keratoprosthesis Implantation Following Autologous Submandibular Gland Transplantation for End Stage Ocular Surface Disorders.

PURPOSE: To describe the results of Boston keratoprosthesis implantation in a patient with Stevens-Johnson syndrome following autologous submandibular gland transplantation. DESIGN: Observational case report. METHODS: We report the case of a man diagnosed with Stevens-Johnson syndrome. Autologous submandibular gland transplantation was performed in the right eye in 2008 to ameliorate tear film deficiency. Due to the improvement in the microenvironment of the ocular surface, Boston keratoprosthesis implantation was performed in the right eye in 2011. RESULTS: He maintained a VA of 20/100 for 12 months. At the last follow-up visit (54 months), his VA had declined to finger count level due to de novo glaucoma, which was treated with glaucoma drainage device implantation, cyclophotocoagulation and topical anti-glaucoma medications. CONCLUSIONS: The procedures described provide patients with end-stage ocular surface disease an option to lessen the severity of keratoconjunctivitis sicca and to regain their VA.

A novel treatment for keratitis sicca (Dry eye): Anatomical feasibility study.

Chronic dry eye (keratitis sicca) is a significant problem that in certain populations can result in corneal desiccation and the potential for blindness. Therefore, novel treatments for such disorders might decrease patient morbidity. The present study aimed to investigate a potential treatment for chronic dry eye via a cadaveric feasibility study. On 10 cadaveric sides, the parotid gland branch of the auriculotemporal nerve (ATN) was identified and anastomosed to an anterior superficial temporal branch (STb) of this same nerve. The STb was then transposed anteriorly and sutured to the lacrimal gland. The parotid branch of the ATN was easily identified on all sides. The STb of the ATN was easily identified and mobilized on all sides. This latter nerve had adequate length to be moved to the ipsilateral lacrimal gland on all sides. Rerouting parotid gland secretomotor fibers to the superficial branch of the ATN and then moving this branch to the lacrimal gland is a feasible surgical maneuver based on our cadaveric study. Clinical studies are now necessary to show utility of this procedure in patients with chronic dry eye. Clin. Anat. 30:839-843, 2017. © 2017Wiley Periodicals, Inc.

Spontaneous Canalicular Plug Erosion After Punctal Plug Placement.

PURPOSE: To describe a case of keratoconjunctivitis sicca treated with punctal plug placement with the first reported complication of subsequent plug erosion through the canaliculus and extrusion through the lid. METHODS: Punctal plugs were placed in a patient with Sjogren syndrome for treatment of keratoconjunctivitis sicca. More than 12 years later, the plug was noted to have eroded through the canaliculus and extruded through the conjunctiva and lid. RESULTS: The extruded plug was removed, and punctal cautery was performed on 2 other puncta with improved symptom control. CONCLUSIONS: Plug extrusion through the conjunctiva and lid is a possible consequence of punctal plug placement.

The Use of Conjunctival Pedicle Flaps to Prevent Corneal Perforation in Graft-Versus-Host Disease.

PURPOSE: We report the clinical outcomes of two chronic graft-versus-host disease (cGVHD) corneal thinning cases that were successfully treated with conjunctival pedicle flaps in an effort to prevent impending corneal perforation. METHODS: The patients were treated with topical and systemic corticosteroids, therapeutic contact lenses, lubricants, and punctual plugs. Conjunctival pedicle flaps were used because conventional treatments had failed, and corneal perforation was imminent. RESULTS: Both patients were successfully treated with conjunctival pedicle flaps. Following conjunctival flap removal, one patient had corneal clarity restored following penetrating keratoplasty. CONCLUSIONS: Conjunctival pedicle flaps provided a strong barrier for the corneal surface and stabilized anterior chamber in cGVHD patients with impending corneal perforation following allogeneic hematopoietic stem cell transplant.

Carbachol improves the secretion of transplanted submandibular glands during the latent period after microvascular autologous transplantation for severe keratoconjunctivitis sicca.

Poor secretion of transplanted submandibular glands (SMGs) during the latent period may cause duct obstruction and affects the surgical outcome. The objective of this study was to investigate the efficacy and systemic side effects of carbachol on transplanted SMG secretion. Twenty-seven patients who underwent SMG transplantation for severe keratoconjunctivitis sicca were treated with subcutaneous injections of 0.2mg/2ml carbachol at 10 days, 1 month, and/or 3 months after surgery. The effect on secretion was evaluated by Schirmer test and technetium 99m ((99m)Tc) scintigraphy. Systemic side effects were evaluated subjectively using a questionnaire. The results showed that the time to onset varied from 4 to 9min and the duration of action from 50 to 110min after carbachol administration. The secretion at each time point after drug administration was significantly higher than the pre-administration value (all P<0.01). (99m)Tc scintigraphy showed a decline in the dynamic time-activity curve in 26 patients, demonstrating a stimulatory effect on the secretion of carbachol. No serious systemic side effects were experienced. In conclusion, the intermittent administration of carbachol could be an effective and safe strategy to promote secretion from transplanted SMGs in the latent period to prevent duct obstruction.

Effects of Capsaicin and Carbachol on Secretion From Transplanted Submandibular Glands and Prevention of Duct Obstruction.

PURPOSE: To investigate whether capsaicin and carbachol promote secretion from and prevent duct obstruction in transplanted submandibular glands (SMGs). METHODS: This retrospective cohort study included consecutive patients with severe keratoconjunctivitis sicca and successful SMG transplantation. Patients were divided into 2 groups: an exposed group receiving both capsaicin and carbachol after surgery and an unexposed group receiving neither. Secretion changes in response to capsaicin and carbachol administration were recorded in the exposed group. The main outcome measures were the secretory flow rate and duct obstruction rate in the transplanted SMGs. RESULTS: Forty-four patients (44 eyes) in the unexposed group and 115 patients (128 eyes) in the exposed group were followed up for more than 3 months postoperatively. The baseline characteristics were similar between the groups. The secretory flow rate before and 5, 25, 55 minutes after administration was 1 mm (0-2 mm) (median with interquartile range), 3 mm (1-5 mm), 4 mm (2-5 mm), 1 mm (0-2.5 mm), respectively, for capsaicin and 1 mm (0-3 mm), 1050 mm (450-1500 mm), 375 mm (150-600 mm), 0 mm (0-150 mm), respectively, for carbachol (P < 0.001 for both). In the exposed group, 6.2% of eyes had duct obstruction, whereas 18.2% of eyes in the unexposed group had duct obstruction (P = 0.031) (odds ratio = 0.3, 95% confidence interval, 0.105-0.856). CONCLUSIONS: This study provides evidence that capsaicin and carbachol effectively promote secretion from and prevent duct obstruction in transplanted SMGs during at least 3 months after transplantation.

Salivary gland scintigraphy in patients suffering from severe keratoconjunctivitis sicca. Evaluation of the viability of submandibular glands before and after transfer into the temporal fossa.

UNLABELLED: Low tear production or elevated tear evaporation can lead to severe keratoconjunctivitis sicca. In patients with this disease, the transfer of an autologous submandibular gland into the temporal fossa is currently the most common surgical lacrimal gland substituting procedure. AIM: We compared the pre- and postoperative viability of transferred submandibular glands. PATIENTS, METHODS: Altogether 16 submandibular glands had been transferred in 12 patients. The graft's viability was evaluated before and 0.5-1, 1-6 and 8-12 months after transplantation by dynamic salivary gland scintigraphies after application of 40-50 MBq 99mTc-pertechnetate. Quantitative analysis was performed by calculation and comparison of the glandula submandibularis-to-background-ratio (SBR) and the transplant-to-background-ratio (TBR). The scintigraphic results were correlated with the clinical follow-up. RESULTS: All grafts remained viable during clinical follow-up. Salivary gland scintigraphy yielded 15 true positive results and 1 false-negative result. Comparison of presurgical SBR and postsurgical TBR showed good correlation with the clinical course. In 10 patients at least one transplant-reduction was necessary due to excessive epiphora occurring averagely 8 months after transplantation. CONCLUSION: Our results show that salivary gland scintigraphy very exactly reflects the morphological and biochemical postsurgical changes in a transferred submandibular gland. Thus, it is a reliable tool to exactly and objectively evaluate the viability of the grafts in the postsurgical course.

The timing of acid-induced increase in saliva secretion in transplanted submandibular glands.

The purpose of this study was to determine the timing of acid-induced increase in saliva secretion and to investigate the possibility of parasympathetic reinnervation of transplanted submandibular glands (SMGs). Citric acid stimulation-induced changes in secretion of transplanted SMGs were evaluated in 27 patients who underwent SMG transplantation for keratoconjunctivitis sicca (KCS); (99m)Tc scintigraphy and Schirmer tests were done at 1, 3, 6, and 9 months after transplantation. Acetylcholinesterase staining was conducted to confirm the presence of parasympathetic reinnervation in three SMGs at 6 and 9 months after transplantation. Schirmer tests showed significantly increased secretion of the transplanted SMGs after acid stimulation at 6 and 9 months, but not at 1 and 3 months. On (99m)Tc scintigraphy, no decline was detected on the dynamic time-activity curve after acid stimulation at 1 and 3 months, but a decline was detected in nine glands at 6 months and in 19 glands at 9 months. No decline was observed in the remaining eight glands at 9 months after transplantation. The histology findings were consistent with scintigraphy results. In conclusion, acid-induced increase in saliva secretion occurs at ≥6 months after SMG transplantation, and parasympathetic reinnervation of the transplanted SMG might occur.

Dry Eye Disease Incidence Associated with Chronic Graft-Host Disease: Nonconcurrent Cohort Study (An American Ophthalmological Society Thesis).

PURPOSE: To determine if chronic graft-versus-host disease (cGVHD) after allogeneic hematopoietic stem cell transplantation (HSCT) is associated with stable or progressive dry eye disease and to determine the true incidence in patients with no prior history of dry eye disease. METHODS: A nonconcurrent cohort study at a single institution with 136 patients who had no previous history of dry eye disease before HSCT. Survival analysis was used to estimate dry eye disease incidence. The incidence rate was calculated using life tables as the number of observed dry eye disease cases divided by the person-time at risk accumulated by the cohort. Transition probabilities were calculated from time of transplant to time of diagnosis, and then to last recorded visit. RESULTS: Incidence rate was 0.8 cases of dry eye disease per person-year, and half of the population at risk developed dry eye disease during the first 10 months post transplant. Time to develop dry eye disease was 2.5 months for mild dry eye disease, 9.6 months for moderate dry eye disease, and 13.2 months for severe dry eye disease. In terms of cumulative incidence, 73% of subjects developed dry eye disease (50% mild, 16% moderate, and 7% severe) at the time of diagnosis. CONCLUSIONS: Our findings suggest that dry eye disease associated with cGVHD is an extremely frequent event and shows a wide spectrum of severity, with a mild form presenting early and a moderate to severe form presenting later after HSCT. These findings need to be studied further to elucidate if these are two different pathophysiological entities or just different expressions of the same pathology.

Obstructive sialadenitis of a transplanted submandibular gland: chronic inflammation secondary to ductal obstruction.

AIMS: To determine the pathological basis and clinical features of obstructive sialadenitis in transplanted submandibular glands (SMGs). METHODS: A total of 161 patients (174 eyes) with keratoconjunctivitis sicca underwent microvascular SMG transplantation. Patients were followed up at approximately 1 and 4 months and annually thereafter. Clinical data, including dry eye discomfort, symptoms of ductal obstruction, and Schirmer test, were recorded. Sialography was performed in six patients. In addition, SMG autotransplantation was performed in 22 rabbits. Salivary flow was recorded and the morphology of glands was examined at 6 months postoperatively by light microscopy. RESULTS: Among the patients, 16 out of 172 glands during the latent period (0-3 months) and 2 out of 154 glands with long-term follow-up (>1 year) showed obstructive sialadenitis. Typical manifestations were continuous small volumes of viscous secretions, recurrent gland swelling, decreased Schirmer test values, and irregular dilation of the main duct on sialography. The transplanted SMGs eventually showed no secretion in five cases. Of the 22 rabbit SMGs, 4 had obstructive sialadenitis. Morphological examination showed chronic inflammatory infiltration with salivary deposits. CONCLUSIONS: Obstructive sialadenitis of transplanted SMGs is a chronic inflammation secondary to ductal obstruction, which leads to insufficient ocular lubrication and potential treatment failure.

Sialography of the transplanted submandibular gland.

Autologous transplantation of submandibular gland (SMG) is effective for severe keratoconjunctivitis sicca (KCS). Sialography is a method for morphological evaluation of the transplanted gland.We recruited 15 patients (15 eyes) with severe KCS who had successfully undergone SMG transplantation. Thirteen patients had normal transplanted SMGs, while two patients were suspected to have obstructive sialadenitis of the transplanted SMG. Sialography was performed in each patient with meglumine diatrizoate. Projections were applied immediately and 5, 7, and 10 min after contrast injection. The median dose of the contrast medium was 0.9 ml (range, 0.7-1.1 ml) for the full-size transplanted SMGs and 0.5 ml for the glands after reduction surgery. The acini and the ducts were clearly visible on sialograms. The contrast medium was completely excreted in 10 min in normal transplanted SMGs. The main duct had a regular shape in normal transplanted SMGs, while irregular dilation and stricture of the duct with delayed excretion of the contrast medium were found in the glands with obstructive sialadenitis. In conclusion, sialography is clinically feasible and valuable for the morphological evaluation of the transplanted SMG.

A new treatment for epiphora secondary to submandibular gland transplantation: transcutaneous atropine gel.

PURPOSE: To explore whether topical application of atropine gel controls epiphora secondary to submandibular gland (SMG) transplantion for severe keratoconjunctivitis sicca. METHODS: Eighteen patients with epiphora after SMG transplantation participated in a double-blind, controlled, crossover study. Patients were treated with topical smear common atropine (CA) and modified atropine (MA) gels (intervals ≥1 day). The control effect of atropine gels was observed for 5 hours. Tear flow was quantified in resting and stimulated (after exercise) states using the Schirmer I test. RESULTS: With the CA gel, tear flow decreased significantly at 10, 30, and 120 minutes. Average epiphora reduction rates (AERRs) were 22.37%, 18.14%, and 13.27%, respectively (P<.05). With the MA gel, tear flow decreased significantly from 5 minutes to 5 hours; AERRs increased from 24.06% to 42.67% (P<.05); Maximum efficacy was maintained from 15 minutes to 3 hours (P<.01); Tear flow gradually increased from 4 to 5 hours but was still lower than that before atropine use (P<.05). According to results of the Schirmer I test and AERRs, the control efficacy of the MA gel was significantly better than that of the CA gel (P<.05). CONCLUSIONS: Topical application of atropine gel could effectively control mild epiphora for patients with SMG transplantation for severe keratoconjunctivitis sicca. The efficacy of MA gel was much better than that of the CA gel.