Evaluating the Effectiveness of Lacrimal Gland Botulinum Toxin Using the TEARS Score.

PURPOSE: Botulinum toxin (BoNTA) lacrimal gland injections are one treatment option for managing epiphora. Outcomes for epiphora in existing studies are subjective and lack grading. This study utilized validated grading instruments to evaluate the efficacy of BoNTA lacrimal gland injections. METHODS: Prospective study evaluating the TEARS score and quality of life in patients receiving incobotulinum toxin (Xeomin) lacrimal gland injections for epiphora. Epiphora was graded using the TEARS score. Quality of life was evaluated using the watery eye quality of life score. Etiology, benefit duration, complications and additional injections were recorded. RESULTS: Of the 28 patients, (median age 67.5 years), 19 (68%) had facial palsy gustatory epiphora (GE). Median effect duration was 13 weeks. Improvements in tearing frequency (T), clinical effects (E), and activity limitation (A) were seen in 57%, 57%, and 71% of patients, respectively. Median watery eye quality of life score improved from 42.4/100 ± 10.1 to 10.6 ± 15.5 (p < 0.001). Alongside crocodile tears, reflex tearing R-scores improved in 68% of patients with GE vs. 11% with non-GE causes (p = 0.004618). In total 89% of patients with GE and 56% with non-GE requested repeat injections. Self-reported percentage improvement ranged from 0% to 100% (median 60%, interquartile range 10%-76.25%). CONCLUSIONS: This is the first study reporting the outcomes of BoNTA lacrimal gland injections using validated TEARS and watery eye quality of life scores. Clinical and quality of life improvements are seen in most patients. Patients with GE achieve an additional improvement in dry eye-related reflex tearing alongside crocodile tears which both improve with BoNTA. TEARS data supports using BoNTA in these patients and is a useful validated grading instrument for epiphora.

Neoadjuvant Intra-arterial Cytoreductive Chemotherapy Improves Outcomes in Lacrimal Gland Adenoid Cystic Carcinoma.

BACKGROUND: Lacrimal gland adenoid cystic carcinoma (LGACC) has historically been associated with a poor prognosis even with localized disease, with a survival of 56% at 5 years. In 1988, we treated the first patient with neoadjuvant intra-arterial cytoreductive chemotherapy (IACC). Since then, we have used this protocol as the standard approach. We aim to analyze the outcomes of patients with LGACC treated with the protocol and compare them to a population-based cohort to assess if IACC can improve survival. METHODS: We prospectively assessed all non-metastatic patients with LGACC treated with IACC at a single institution between 1988 and 2021. For a comparison group, we identified all non-metastatic patients with LGACC treated with excision from the Surveillance, Epidemiology, and End Results (SEER) registry. We calculated disease-specific survival using the Kaplan-Meier and Cox proportional-hazards modeling methods. RESULTS: Thirty-five non-metastatic patients with LGACC treated with IACC were identified at a single institution, and 64 patients with non-metastatic LGACC treated with excision were identified in the SEER database. The 5- and 10-year disease-specific survival rates for patients treated with IACC were 84% (95%CI 71-97) and 76% (95%CI 60-92), respectively. While the 5- and 10-year disease-specific survival rates for the population-based cohort were 72% (95%CI 62-82) and 46% (95%CI 32-60). The survival analysis favored IACC, with a 60% lower risk of death (HR: 0.4; 95%CI 0.2-0.9). CONCLUSION: IACC improves disease-specific survival in comparison to a population-based cohort treated with excision. Additional patients treated with IACC at multiple institutions are required to provide further external validity.

Lacrimal gland targeted therapies for refractory epiphora: quantitative changes in the gland activity.

PURPOSE: To investigate the effect of botulinum toxin (BTX) and partial orbital lobe dacryoadenectomy (POLD) on the main lacrimal gland functions using the direct assessment of its secretory activity. METHODS: A pilot study involving 14 subjects (mean age, 42.16 years) with proximal bicanalicular block (n = 9) or complete punctal effacement (n = 5) received either intraglandular 2.5 units of BTX (n = 7) or underwent the POLD procedure (n = 7). Dynamic assessment of tear secretion from the palpebral lobes was performed as per standard protocols. The parameters studied included Schirmer I, changes in the glandular outflow, and the neurosensory secretory lag. RESULTS: Schirmer I values showed a mean reduction of 5.25 mm (range, 2-8 mm) following BTX injection, and mean tear flow decreased from 1.46 µl/min to 1.11 µl/min (P = 0.15). The POLD group showed a significant mean reduction of 0.45 µl/min in mean tear flow at 1 month (P = 0.03) and 0.32 µl/min at 3 months of follow-up (P = 0.20). However, there was no statistically significant change of the Schirmer values in the POLD group at 3 months. CONCLUSION: Direct assessment of lacrimal gland function can be used to monitor changes following the gland therapies. Although POLD shows a significant reduction in short term, significant surgical improvisation would be needed for it to be effective in long term. A larger study is ongoing to further our understanding.

Long-term Follow-up Results of Primary Canaliculitis Patients.

Objectives: To evaluate the demographic characteristics, clinical presentation, microbiologic profile, and treatment results of patients with primary canaliculitis. Materials and Methods: Patients diagnosed and treated for primary canaliculitis between May 2014 and May 2021 were analyzed retrospectively. Results: There were 26 patients with primary canaliculitis, including 17 females (65.4%) and 9 males (34.6%) with a mean age of 50.6±16.4 years (range: 9-80 years). Canaliculitis affected the right eye in 11 patients, the left eye in 13 patients, and bilateral involvement was seen in 2 patients. Inferior canaliculus involvement was more frequent (73%). The most common complaint was epiphora (46.1%). Five patients (19.2%) were wrongly diagnosed as chronic conjunctivitis. The time interval between the beginning of symptoms and canaliculitis diagnosis was 18.2±14.3 months (range: 1-60 months). Canaliculotomy and curettage of canalicular content with dacryolith removal were performed in 23 patients. After surgery, antibiotic irrigation of the canaliculus was added to the treatment regimen in 12 of these 23 patients. Intracanalicular antibiotic therapy was administered to the remaining 3 patients. The most cultured organism was Actinomyces (6 patients). Gemella (1 patient), Porphyromonas (1 patient), Candida parapsilosis (1 patient), Citrobacter koseri (1 patient) were also grown in culture. The follow-up time of patients was 26.2±23.7 months (range: 6-83 months). All symptoms and findings resolved in all patients in one month. In two patients, recurrence occurred at 4 and 16 months after surgical treatment. With appropriate treatment, no further recurrence was seen in either patient over 24-month follow-up. One patient presented with iatrogenic canaliculus blockage during follow-up. Conclusion: Primary canaliculitis is often overlooked and can be misdiagnosed. The most common symptom was epiphora. All patients with epiphora and chronic conjunctivitis should be examined carefully for canaliculitis.

Crocodile tear syndrome treated with lacrimal gland incobotulinum toxin A injection: a report of two cases.

Crocodile tear syndrome (CTS) is a late complication of facial nerve palsy characterized by unilateral lacrimation in response to gustatory stimulation. We present 2 cases of patients diagnosed with CTS after recovering from unilateral idiopathic facial nerve palsy. Both patients underwent transconjunctival lacrimal gland incobotulinumtoxinA injection, with doses of 5-16 units. The patients were seen in clinic for post-treatment follow-up at 2 weeks, 3 months, and 6 months. Outcomes were measured by treatment efficacy and adverse drug effects. Following treatment, both patients reported resolution of gustatory lacrimation. The patient treated with 16 U experienced transient ptosis and diplopia following injection, whereas the patient treated with 5-7.5 U experienced no adverse effects.

The Importance of Preventing and Managing Tear Dysfunction Syndrome in Allergic Conjunctivitis and How to Tackle This Problem

Tear dysfunction syndrome, also known as dry eye disease (DED), is a multifactorial disease of the ocular surface characterized by the loss of tear film homeostasis. DED shows a significant clinical overlap with ocular allergy (OA), which alters tear film homeostasis, thus predisposing the patient to DED. Both conditions constitute the most common ocular surface disorders and have a potentially severe impact on patients’ quality of life. Clinical practice guidelines recommend topical therapies as first-line treatment for OA. However, eye drop formulations may contain additional substances that can contribute to ocular surface damage and the development of DED. Therefore, physicians treating ocular allergy should be aware of problems affecting the tear film, the role of tear film disruption in OA, and topical treatment to prevent or minimize DED. The aim of this review is to present an updated overview of the topic. (AU)

El síndrome de disfunción lagrimal, también denominado enfermedad del ojo seco (EOS), es una enfermedad multifactorial de la superficie ocular caracterizada por la pérdida de la homeostasis de la película lagrimal. La EOS y la alergia ocular (AO) son patologías que comparten un abanico de signos y síntomas, y pueden aparecer simultáneamente; además, la AO altera la homeostasis de la película lagrimal, predisponiendo a la EOS. Estas dos afecciones constituyen los trastornos más frecuentes de la superficie ocular y pueden afectar notablemente la calidad de vida de los pacientes. Las guías de práctica clínica recomiendan terapias tópicas como tratamiento de primera línea para la alergia ocular. Sin embargo, las fórmulas de los colirios pueden contener aditivos y conservantes que pueden contribuir al daño de la superficie ocular y a la aparición de EOS. Por lo tanto, los facultativos que tratan la alergia ocular deben conocer las implicaciones que conlleva la alteración de la película lagrimal en la conjunctivitis alérgica, el potencial daño que pueden provocar los conservantes incluidos en los colirios empleados en el tratamiento tópico de esta patología, así como los tratamientos disponibles para manejar la EOS y la AO cuando la disfunción de la película lacrimal ya está establecida. El objetivo de esta revisión es presentar una visión general actualizada del tema. (AU)

Tratamiento de la epífora funcional con toxina botulínica tipo A frente a la tira tarsal en un ensayo aleatorizado / Treatment for functional epiphora with botulinum toxin-A versus lateral tarsal strip in a randomized trial

Objetivo Comparar la eficacia de la inyección de toxina botulínica A (TBA) en la glándula lagrimal con la tira tarsal lateral (TTL) en la epífora funcional. Material y método Ensayo clínico aleatorizado. Diseño secuencial, paralelo y no ciego. Pacientes de 18 años o más con epífora funcional con un mínimo de 3 en la escala de Munk (EM) se incluyeron a grupo de TBA o TTL. Los cambios en la EM, el test de Schirmer y la calidad de vida se evaluaron a la semana 6 y hasta la semana 30. Se obtuvo el tiempo medio sin epífora y los acontecimientos adversos. Resultados El análisis final incluyó 25 pacientes, 12 (21 ojos) se asignaron a TBA (5U/0,05mL) y 13 (20 ojos) a TTL. A la semana 6 hubo un mayor descenso en la EM en el grupo de TBA frente a TTL (−2.48 vs. −1.55, p=0,0152) y a la semana 12 (−2,68 vs. −1,69, p=0,0267). Se observó un descenso significativo en el test de Shirmer a las semanas 2, 12 y 30 con TBA. La calidad de vida mejoró después de ambas intervenciones, sin diferencias significativas. El tiempo medio sin epífora en el grupo TBA fue de 26,2 semanas (7,7-36,6) y en el grupo TTL de 24,8 semanas (6,7-37,6), p=0,9368. Se observó ptosis temporal en un 25% (3/12) en el grupo TBA y un 23% (3/13) de molestias de la cicatriz quirúrgica en el grupo TTL, p=0,722. Ningún acontecimiento adverso fue severo. Conclusión La inyección de TBA en la glándula lagrimal es efectiva y segura en el tratamiento de la epífora funcional, con mayor descenso en la EM a las 6 y 12 semanas comparado con la TTL (AU)

Objective To compare the efficacy of botulinum toxin A (BoNTA) injection into the lacrimal gland versus lateral tarsal strip (LTS) for functional epiphora Material and methods Randomized clinical trial. Sequential, parallel, non-blinded study design. Patients aged 18 years or older with functional epiphora and a minimum score of 3 in Munk Scale (MS) were randomized to BoNTA or LTS group. Changes in MS, Schirmer test and quality of life were assessed at week 6 and during follow-up until week 30. The mean time without epiphora and the adverse events were recorded. Results The final analysis included 25 patients, 12 (21 eyes) assigned to BoNTA (5U/0.05mL) and 13 (20 eyes) to LTS. At 6 weeks there was an improvement in the MS in BoNTA versus LTS group (−2.48 vs. −1.55, P=.0152) and at 12 weeks (−2.68 vs. −1.69, P=.0267). A significant decrease was noted in the Schirmer test at week 2, 12 and 30 with BoNTA. The quality of life improved after both interventions without statistical significance. The mean duration of effectiveness in BoNTA group was 26.2 weeks (range 7.7-36.6) and in LTS group was 24.8 weeks (range 6.7-37.6), P=.9368. The main adverse events were temporary eyelid ptosis in 25% (3/12) of the BoNTA group and surgical scar discomfort in 23% (3/13) of the LTS group, P=.722. No adverse events were classified as severe. Conclusion BoNTA injection into the lacrimal gland is a safe and effective treatment for functional epiphora, with a greater decrease in MS at 6 and 12 weeks compared with LTS (AU)

[Current clinical application of lacrimal gland injection of botulinum toxin type A in inhibiting lacrimal secretion].

Lacrimal gland injection of botulinum toxin type A inhibits the secretion of tears. As a new method to treat or alleviate the symptom of tears or epiphora, it has the characteristics of simple operation, definite curative effect, repeatable treatment and no irreversible complications. It provides an optional treatment scheme for many patients with refractory tears or epiphora. This article reviews the pharmacological characteristics of botulinum toxin type A, the mechanism of inhibiting tear secretion, the method and dose of lacrimal gland injection, indications and contraindications, clinical efficacy evaluation, complications, existing problems to be solved and prospects for reference.

Neoadjuvant Intra-Arterial Cytoreductive Chemotherapy for Lacrimal Gland Adenoid Cystic Carcinoma: A Long-Term Follow-up Study of a Trimodal Strategy.

PURPOSE: To report the therapeutic efficacy of integrating neoadjuvant chemotherapy with conventional bimodal therapies for lacrimal gland adenoid cystic carcinoma by providing an additional 8 years of follow-up data on the same cohort of patients whose cumulative 10-year disease-free survival outcomes were reported in 2013. DESIGN: Non-randomized, retrospective, interventional case series. METHODS: Nineteen consecutive patients treated with neoadjuvant intra-arterial cytoreductive chemotherapy (IACC), orbital exenteration, chemoradiotherapy, and adjuvant intravenous chemotherapy at a single institution were included. Analyses were undertaken of locoregional recurrences and distant metastases, disease-free survival time, TNM tumor stage at presentation, response to IACC, and prognostic impact of positive resection margins. The main outcome measures were overall survival, disease-free survival, disease relapse, positive tumor resection margins, and tumor stage at presentation. RESULTS: Eight patients with an intact lacrimal artery (group 1), 7 with AJCC stage T4a-c, had significantly better overall survival (87.5% versus 14.3% at 15 years), disease-specific mortality, and recurrences (all < .001, log-rank test) than prior conventionally treated patients from the Bascom Palmer Eye Institute. Group 1 was superior to group 2, patients lacking an intact lacrimal artery, concerning overall survival (P = .042) and recurrence (P = .017), but with no significant difference in disease-specific mortality (P = .23). Group 2 was associated with a significantly lower cause-specific mortality than the institutional comparator group (P = .039). Prior tumor resection with lateral wall osteotomy and failure to adhere to all protocol elements were adverse prognostic factors for suboptimal outcomes. Positive tumor margins increased the risk of all-cause mortality 4.1 times (P = .036, stratified Cox proportional hazards regression) and disease-specific mortality 8.0 times (P = .043, stratified Cox proportional hazards regression) than a patient with negative margins. CONCLUSIONS: Extended follow-up supplemented with AJCC staging data supports neoadjuvant IACC as an integral component of a trimodal treatment strategy in patients with an intact lacrimal artery. Protocol elements implemented as designed appear to have improved overall survival and decreased disease relapse in this cohort. This extended long-term IACC dataset suggests that a critical bar of at least 15 years of follow-up is appropriate for assessing the efficacy of current conventional and future globe-sparing bimodal therapies.

Topography of the orbital part of the lacrimal gland for treating epiphora using botulinum toxin injection.

The purpose of this study is to identify the location of the orbital part of the lacrimal gland using external landmarks to facilitate effective botulinum toxin A (BTX-A) injections for epiphora treatment. Dissections were performed on 45 hemifaces from 27 cadavers. The length, anterior protrusion, and thickness of the orbital part of the lacrimal gland were measured directly. The midpoint of the line running horizontal through the medial and lateral canthus was used as the horizontal reference point. Vertical lines perpendicular to the midpoint of the horizontal reference line were the vertical reference lines. The angles from the horizontal reference line to the lacrimal gland center and to the frontal tubercle were also measured. The length and thickness of the lacrimal gland were 12.8 and 2.4 mm, respectively. The lacrimal gland had an anterior protrusion of 4.1 mm from the superolateral orbital margin. The superior and inferior margins of the lacrimal gland were located 35.7° and 15.8° from the two reference lines, respectively. The angle from the horizontal reference line to the lacrimal gland center was 35.1°, which was similar to that to the frontal tubercle (34.4°). The orbital part of the lacrimal gland was more inferior in elderly subjects and the angle between the horizontal reference line and its center was 35.1°, which was similar to the location of the frontal tubercle. The location of this tubercle can help clinicians to perform BTX-A injections into the lacrimal gland, thereby enhancing the effectiveness of epiphora treatment.

Transconjunctival botulinum toxin injection into the lacrimal gland in crocodile tears syndrome.

Purpose: To determine the efficacy and safety of botulinum toxin injection into the lacrimal gland as a symptomatic treatment of crocodile tear syndrome (CTS). Methods: Our study included six patients of unilateral gustatory hyper lacrimation following either an episode of facial paralysis or post trauma or any related surgery that posed a risk of damaging the facial nerve. Detailed history regarding previous trauma, duration of facial paralysis, previous significant surgery, and duration of steroid use following facial paralysis was noted. Schirmer's test was done at baseline and 3 months follow-up. Patients' consent was taken prior to treatment with botulinum toxin injection in the lacrimal gland. Repeat injection of 5 U botulinum toxin (type A) was administered into the lacrimal gland of all patients transconjunctivally within an interval of 1 week. All patients were followed up with Schirmer's test at 6 weeks and 3 months. Any complications during treatment were recorded. Results: All six patients showed complete or partial disappearance of reflex lacrimation while chewing following botulinum injection measured by a significant reduction in Schirmer's value. When comparing Schirmer test values before (27.8 ± 3.58 mm) and after (11.6 ± 2.28 mm) BTX-A injection, the differences observed (P = 0.002) were statistically significant (P < 0.05). Only two patients developed mild transitory ptosis. No other complications were noted. Conclusion: Transconjunctival botulinum toxin injection into the lacrimal gland is an effective and safe method to decrease reflex lacrimation during eating or chewing in CTS or gustatory hyper-lacrimation syndrome.

Genome Sequencing and Apoptotic Markers to Assess Treatment Response of Lacrimal Gland Adenoid Cystic Carcinoma to Intra-Arterial Cytoreductive Chemotherapy.

Adenoid cystic carcinoma of the lacrimal gland is an aggressive, malignant epithelial neoplasm. We report the case of a 30-year-old male with lacrimal gland adenoid cystic carcinoma treated with neoadjuvant intra-arterial chemotherapy through the internal carotid artery, followed by orbital exenteration and chemoradiation. Treatment response was evaluated using a novel combination of pre- and posttreatment genome sequencing coupled with immunohistochemical evaluation, which showed diffuse tumor apoptosis. A posttreatment decrease in variant allele frequency of the NOTCH1 mutation, and robust tumor cytoreduction on imaging, supports exploration of NOTCH1 analysis as a potential marker of cisplatin sensitivity. The use of genome sequencing and immunohistochemical evaluation could provide a more targeted therapeutic assessment of neoadjuvant intra-arterial chemotherapy in the management of lacrimal gland adenoid cystic carcinoma.

Could Extension Into the Lacrimal Gland and Sac Thwart Topical Chemotherapy for Intraepithelial Sebaceous Carcinoma?

PURPOSE: To identify the frequency of intraepithelial (Pagetoid) spread beyond the ocular surface-namely beyond conjunctiva and cornea-in patients undergoing orbital exenteration for advanced periocular Sebaceous carcinoma (SC). DESIGN: A retrospective, noncomparative observational case series. SUBJECTS: Patients undergoing orbital exenteration for biopsy-proven SC, at Moorfields Eye Hospital between 1997 and 2013. METHODS: Review of clinical records and histological specimens, with particularly reference to involvement of conjunctiva and the extent of Pagetoid infiltration beyond the examinable ocular surface-here termed "hidden" disease. MAIN OUTCOME MEASURES: Histological evidence of intraepithelial SC within the lacrimal sac or lacrimal gland. RESULTS: Twenty-nine patients had clinical data and histological specimens adequate for review. Seventeen (59%) did not have a discrete mass (clinically or histologically) and, on clinical examination, were thought to only have extensive intraepithelial carcinoma; foci of microscopic invasion were, however, detected histologically in 11/17 (65%) of these specimens. Moreover, the in situ carcinoma was found to have invaded far in lacrimal gland ductules in 1/17 patients, in the lacrimal sac (in 2 patients; 12%) or in both the gland and sac (in 2 patients); these 5/17 (29%) cases all showed extensive poorly differentiated intraepithelial SC. Of the 12 other patients who had both Pagetoid spread and a clinically evident nodule, 3 had histological evidence of "hidden" disease. CONCLUSION: Although-due to their being operated in the era prior to the accepted usage of topical therapy for this condition-some of these exenterations might have had particularly advanced in situ SC, over a quarter of patients with periocular SC warranting orbital exenteration show "hidden" intraepithelial tumor within the lacrimal gland and sac. This important finding might significantly reduce the efficacy (particularly in the lacrimal gland) of the various topical therapies used for in situ SC of the ocular surface, and it also emphasizes the importance of excising both the lacrimal gland and sac in all orbital exenterations for this particular tumor.

Conjunctival Infiltration in a Child as a Rare Manifestation of IgG4-Related Disease.

PURPOSE: Ocular manifestations of immunoglobulin G4 (IgG4)-related disease are common in children although remain ill-defined because of the disease's rarity. We describe a pediatric case of IgG4-related orbital disease (IgG4-ROD) who presented with persistent conjunctival infiltration before developing lacrimal gland enlargement 3 years later. METHODS: This was a case report. RESULTS: An 8-year-old girl developed forniceal salmon-patch-like conjunctival lesions in her left eye that were refractory to topical corticosteroids. Investigations, including an orbital MRI and 2 conjunctival biopsies, were negative for lymphoma. She was treated with topical corticosteroids and then nonsteroidal antiinflammatory drops. The lesions decreased mildly, and no new lesion emerged. After 3 years, the patient developed a ptosis, new salmon-patch conjunctival lesions, and papillae. Vision deteriorated to 20/80 because of severe punctate epithelial erosions in the left eye, and the Schirmer test was significantly reduced. A repeat MRI revealed an enlarged left lacrimal gland. A biopsy was performed and was compatible with IgG4-ROD. An elevated IgG4 level of 4.61 g/L was also found. The patient was successfully treated with oral prednisone but flared on tapering the dosage. Rituximab was therefore initiated with excellent clinical response, and prednisone was discontinued. Vision returned to 20/20 after aggressive lubrification, punctal plugs, and autologous serum eye drops. Tear function came back to normal, and local treatments were stopped. CONCLUSIONS: This case describes a pediatric case of IgG4-ROD presenting initially with conjunctival follicular reaction, later developing lacrimal gland involvement. Therefore, it is important to consider IgG4-ROD in chronic atypical follicular conjunctival lesions in children, even in the absence of orbital disease.

Targeted Neoadjuvant Intra-arterial Chemotherapy in Lacrimal Gland Adenoid Cystic Carcinoma: A Histological Correlation Using Apoptotic Tumor Markers.

Neoadjuvant intra-arterial cytoreductive chemotherapy is used for the treatment of lacrimal gland adenoid cystic carcinomas (ACC) to improve outcomes in this condition with an otherwise dismal prognosis. We share our experience in the management of an advanced case of ACC using a novel, highly targeted intra-arterial cytoreductive chemotherapy delivery technique involving both the internal and external carotid circulation, with an attempt to correlate the effect histologically. Refinement of the chemotherapy delivery using the tumor's vascular anatomy and appropriate blood vessel selection may lead to future globe sparing procedures without compromising survival.

Primary Melanoma of the Lacrimal Sac Treated With Pembrolizumab.

Primary melanoma of the lacrimal sac is a rare entity, with high mortality and a propensity for recurrence. This report details a patient with widely metastatic melanoma discovered after biopsy of abnormal lacrimal sac tissue during routine dacryocystorhinostomy. The patient subsequently underwent local excision and treatment with pembrolizumab. At the time of this writing, it has been 24 months since the original diagnosis with resolution of his lacrimal and orbital lesions and improvement in all metastatic lesions. This case highlights the growing use of cancer genomics and immunotherapeutic agents in orbital aspects of oncology and reinforces the role of a multidisciplinary approach in the treatment of such diseases.

The Effect of Resveratrol on Radioiodine Therapy-Associated Lacrimal Gland Damage.

PURPOSE: We have evaluated the potential radioprotective, antioxidant and anti-apoptotic effects of resveratrol (RSV) against high-dose radioactive iodine (RAI) therapy associated damage of the lacrimal glands by biochemical, histopathological and immunohistochemical methods. MATERIALS AND METHODS: Thirty Wistar-albino rats were randomly divided into three groups; the control group received no treatment or medication, the RAI group received RAI but no medication and the RSV group received oral RAI and intraperitoneal RSV. RSV was started at day one, before RAI administration, and continued for 8 days. Bilateral intraorbital (IG), extraorbital (EG), and Harderian (HG) lacrimal glands were evaluated in all rats for histopathological, immunohistochemical, tissue cytokine and oxidant and antioxidant level assessment. RESULTS: RSV group restored inflammation, fibrosis, vacuolization, change in nucleus characteristics, lipofuscin-like accumulation and cellular morphologic patterns were statistically significant in all lacrimal gland types, compared to the RAI group (p < .05 for all variables). Similarly, elevated Caspase-3 and TUNEL levels in the RAI group were significantly alleviated in the RSV group in all lacrimal gland types (p < .05 for all variables). RAI administration significantly elevated TNF-α, IL-6, NF-кb levels, and decreased IL-10 levels (p < .05 for all parameters) whereas TOS levels significantly increased and TAS levels were significantly decreased. However, RSV significantly diminished TNF-α, IL-6, IL-4, and NF-кb levels. Furthermore, RSV significantly decreased TOS and increased TAS levels (p < .05 for all variables). CONCLUSIONS: We conclude that with its anti-cancer effect as well as its antioxidant effect RSV has protected the histopathological pattern of the lacrimal glands from the damage, decreased inflammation in histopathologic assessments, and decreased tissue cytokine levels, apoptosis and DNA fragmentation on the lacrimal glands after RAI.

Histopathologic Observations of Eyes in Exenterated Orbits After Neoadjuvant Intra-Arterial Cytoreductive Chemotherapy for Adenoid Cystic Carcinoma of the Lacrimal Gland.

PURPOSE: To assess whether exenteration specimens obtained after neoadjuvant intra-arterial cytoreductive chemotherapy (IACC) for adenoid cystic carcinoma of the lacrimal gland demonstrate significant ocular histopathologic alterations that might preclude future pursuit of globe-preserving therapy. METHODS: Retrospective histopathologic analysis of globes in IACC-treated exenteration specimens among the same cohort of patients whose survival outcomes have been reported. RESULTS: Twenty patients had specimens available. Nineteen globes revealed no abnormalities of the iris, ciliary body, lens, retinal pigment epithelium, choroid, or chorioretinal vasculature. Eighteen globes showed no optic nerve abnormalities. One globe from a patient who refused exenteration until adenoid cystic carcinoma recurrence supervened demonstrated optic nerve edema with a peripapillary hemorrhage and cotton wool spot, as well as hemorrhage and necrosis within an extraocular muscle. Eighteen globes showed no retinal abnormalities attributable to intra-arterial chemotherapy. Three globes showed incidental retinal findings: 2 globes contained 1 to 2 small peripheral retinal hemorrhages and 1 had a pigmented retinal hole. Seven demonstrated mild, chronic extraocular muscle inflammation, and 13 had unremarkable musculature. The single patient who received IACC via the internal carotid rather than the external carotid artery developed ophthalmic artery occlusion with orbital apex syndrome prior to exenteration, and diffuse necrosis and hemorrhage were evident histopathologically. CONCLUSIONS: Neoadjuvant IACC does not cause significant histopathologic damage to key ocular structures or compromise visual function in patients receiving intra-arterial chemotherapy through the external carotid artery. However, delivering chemotherapy through the internal carotid artery may result in visually significant thrombotic vascular events. The generally benign histopathological findings in these exenteration specimens support the concept of IACC delivery through the external carotid system as the cornerstone of a future globe-preserving strategy for lacrimal gland adenoid cystic carcinoma.