Prognostic Significance of Tumor-Infiltrating Lymphocytes and High-Risk Human Papillomavirus in Ocular Sebaceous Carcinoma: A Comprehensive Analysis.

High-risk human papillomavirus (hrHPV) and tumor-infiltrating lymphocytes (TILs) are known to have prognostic significance in oropharyngeal squamous cell carcinoma. However, their significance in ocular sebaceous carcinoma (OSC) remains unverified because of the rarity of the condition. This study aimed to investigate the association between clinicopathologic features, biomarkers, and hrHPV infection and their potential to predict prognosis in OSC patients. We analyzed the clinicopathologic features of 81 OSC patients from Asan Medical Center between 2000 and 2022. Seventeen biomarkers and hrHPV were examined using immunohistochemistry and DNA in situ hybridization on tissue microarray cores. hrHPV was identified in 31 cases (38.3%). Univariate analysis revealed that hrHPV infection was associated with comedonecrosis (P = .032), high Ki-67 labeling index (≥30%, P = .042), lower expression of E-cadherin (P = .033), and loss of expression of zinc finger protein 750 (P = .023). Multivariate analysis revealed that loss of expression of zinc finger protein 750 (P = .026) remained an independently associated factor for hrHPV. Progression-free survival analysis was performed on 28 patients who were continuously observed for more than 5 years. During a median follow-up duration of 86 months, recurrence or metastasis developed in 14 patients (50%) within the survival cohort, occurring at a median time of 48 months after excision. Univariate analysis indicated that recurrence or metastasis was associated with tumor size (P = .010), high TILs (≥10%; P = .025), lymphovascular invasion (P = 0.043), site of origin (P = .025), and high expression of bcl-2-associated athanogene 3 (P = .039). Multivariate analysis demonstrated that high TILs (P = .017) and site of origin (P = .025) were independent prognostic factors. The prognosis of OSC was hrHPV-independent, and a better prognosis was associated with the site of origin in the order of the gland of Zeis, meibomian gland, and multicentric site, as well as with high TILs.

Efficacy and safety of intravenous glucocorticoid therapy for IgG4-related ophthalmic disease.

PURPOSE: To evaluate and compare the efficacy and safety of intravenous (IV) glucocorticoid therapy with those of oral glucocorticoids as a first-line treatment for IgG4-related ophthalmic disease (IgG4-ROD). METHODS: We retrospectively reviewed the medical records of patients who underwent systemic glucocorticoid therapy for biopsy-proven IgG4-ROD from June 2012 to June 2022. Glucocorticoids were given either oral prednisolone at an initial dose of 0.6 mg/kg/day for four weeks with subsequent tapering or once weekly IV methylprednisolone (500 mg for six weeks, then 250 mg for six weeks), according to the date of treatment. Clinicoserological features, initial response, relapse during follow-ups, cumulative doses of glucocorticoids, and adverse effects of glucocorticoids were compared for the IV and oral steroid groups. RESULTS: Sixty one eyes of 35 patients were evaluated over a median follow-up period of 32.9 months. The complete response rate was significantly higher in the IV steroid group (n = 30 eyes) than in the oral steroid group (n = 31 eyes) (66.7% vs. 38.7%, p = 0.041). Kaplan-Meier analysis showed that the 2-year relapse-free survival was 71.5% (95% confidence interval: 51.6-91.4) and 21.5% (95% confidence interval: 4.5-38.5) in the IV steroid and oral steroid group, respectively (p < 0.001). Although the cumulative dose of glucocorticoids was significantly higher in the IV steroid group than in the oral steroid group (7.8 g vs. 4.9 g, p = 0.012), systemic and ophthalmic adverse effects were not significantly different between the two groups throughout follow-ups (all p > 0.05). CONCLUSIONS: As a first-line treatment for IgG4-ROD, IV glucocorticoid therapy was well-tolerated, led to better clinical remission and more effectively prevented inflammatory relapse than oral steroids. Further research is needed to establish guidelines on dosage regimens.

Effectiveness of An Intraoperative Lagophthalmos Formula for Levator Resection in Patients With Congenital Ptosis.

PURPOSE: To evaluate the effectiveness of an intraoperative lagophthalmos formula (IOLF) for levator resection in congenital ptosis and investigate the optimal preoperative conditions for IOLF application. METHODS: This retrospective interventional cohort study evaluated 30 eyelids of 22 patients with congenital ptosis who underwent levator resection using the IOLF to calculate the extent of surgical correction under general anesthesia. Surgical success was defined as margin reflex distance-1 (MRD1)≥3 mm in each eye and a difference of MRD1 1 mm between the eyes at 6 months postoperatively. Logistic regression was performed to investigate the preoperative conditions associated with surgical success. RESULTS: Among 30 eyelids, 19 had good-to-fair levator function (LF) (≥5 mm) and 11 had poor LF ( 4 mm). The overall success rate was 90.0% (n=27/30), whereas the under-correction rate was 10.0% (n=3/30). The surgical success rate was 100% (n=19/19) in eyelids with LF ≥5 mm and 72.7% (n=8/11) in eyelids with LF 4 mm. Patients with preoperative MRD1≥0 mm (versus MRD1<0 mm, odds ratio=34.5, P =0.0098) or a combination of preoperative MRD1≥0 mm and LF≥5 mm (versus MRD1<0 mm and LF 4 mm, odds ratio=48.0, P =0.0124) more likely had successful surgical outcomes. CONCLUSIONS: Levator resection using the IOLF can provide satisfactory results for congenital ptosis regardless of LF. Preoperative MRD1≥0 mm may be suitable for IOLF application, and the combination of preoperative MRD≥0 mm and LF≥5 mm may be the optimal preoperative condition for IOLF application.

Clinical and Radiological Features of Diffuse Lacrimal Gland Enlargement: Comparisons among Various Etiologies in 91 Biopsy-Confirmed Patients.

OBJECTIVE: To compare the clinical and radiological features of various etiologies of chronic diffuse lacrimal gland enlargement. MATERIALS AND METHODS: We retrospectively reviewed 91 consecutive patients who underwent surgical biopsy for chronic diffuse lacrimal gland enlargement and were diagnosed with non-specific dacryoadenitis (DA) (n = 42), immunoglobulin G4-related dacryoadenitis (IgG4-RD) (n = 33), and lymphoma (n = 16). Data on patient demographics, clinical presentation, and CT imaging findings (n = 73) and MRI (n = 43) were collected. The following radiologic features of lacrimal gland enlargement were evaluated: size, unilaterality, wedge sign, angle with the orbital wall, heterogeneity, signal intensity, degree of enhancement, patterns of dynamic contrast-enhanced, and apparent diffusion coefficient value. Radiological features outside the lacrimal glands, such as extra-lacrimal orbital involvement and extra-orbital head and neck involvement, were also evaluated. The clinical and radiological findings were compared among the three diseases. RESULTS: Compared to the DA and IgG4-RD groups, the lymphoma group was significantly older (mean 59.9 vs. 46.0 and 49.4 years, respectively; p = 0.001) and had a higher frequency of unilateral involvement (62.5% vs. 31.0% and 15.2%, respectively; p = 0.004). Compared to the IgG4-RD and lymphoma groups, the DA group had significantly smaller lacrimal glands (2.3 vs. 2.8 and 3.3 cm, respectively; p < 0.001) and a lower proportion of cases with a wedge sign (54.8% vs. 84.8% and 87.5%, respectively; p = 0.005). The IgG4-RD group showed more frequent involvement of the extra-orbital head and neck structures, including the infraorbital nerve (36.4%), paranasal sinus (72.7%), and salivary gland (58.6%) compared to the DA and lymphoma groups (4.8%-28.6%) (all p < 0.005). CONCLUSION: Patient age, unilaterality, lacrimal gland size, wedge sign, and extra-orbital head and neck involvement differed significantly different between lymphoma, DA, and IgG4-RD. Our results will be useful for the differential diagnosis and proper management of chronic lacrimal gland enlargement.

Update on Immune Checkpoint Inhibitors for Conjunctival Melanoma.

The management of conjunctival melanoma is challenging due to the more frequent local recurrence and metastasis compared to other conjunctival neoplasms. Locally advanced conjunctival melanoma may require an orbital exenteration, and treatment options for metastatic conjunctival melanoma have been limited until recently. This review aims to provide comprehensive updates on immunotherapy for conjunctival melanoma, focusing on immune checkpoint inhibitors. We reviewed the available literature on the use of immunotherapy for the treatment of conjunctival melanoma. Systemic immunotherapy, particularly with checkpoint inhibitors, has recently been reported to have improved outcomes for patients with conjunctival melanoma. Immune checkpoint inhibitors that are currently approved by the US Food and Drug Administration for melanoma include anti-PD-1 (nivolumab and pembrolizumab), anti-PDL-1 (avelumab and atezolizumab), and anti-CTLA-4 inhibitors (ipilimumab). Most recent reports described using immune checkpoint inhibitors in patients with locally advanced conjunctival melanoma in an attempt to avoid orbital exenteration or in patients with metastatic conjunctival melanoma.Although the current data are limited to case reports and small case series, eye care providers should be aware of the potential role of immunotherapy for patients with locally advanced, recurrent, or metastatic conjunctival melanoma.

Quantitative analysis of morphological and functional alterations of the meibomian glands in eyes with marginal entropion.

PURPOSE: To quantitatively analyze morphological and functional alterations of the meibomian glands in eyes with marginal entropion and their changes after surgery. METHODS: Sixty eyes of 52 patients with marginal entropion and underwent meibography and interferometer were included. One-hundred and seventeen age- and sex-matched eyes with minimal to mild meibomian gland dysfunction (MGD) were recruited as control eyes. Meibomian gland loss (MGL) and lipid layer thickness (LLT) were compared between eyes with marginal entropion and control eyes. Subgroup analysis was performed according to the extent of entropion. MGL and average LLT at 1 and 5 months after surgery were compared with those of 20 eyes with marginal entropion followed without surgery. RESULTS: In eyes with marginal entropion, MGL was higher (27.7% vs. 12.8%, P = 0.014), and average LLT was thinner (64 nm vs. 86 nm, P = 0.005) than those in control eyes. MGL was higher in eyes with more extensive entropion (> 2/3 eyelid width) than in eyes with less extensive entropion (≤ 1/3 eyelid width) (40.5% vs. 13.2%, P = 0.001). Average LLT increased after surgery (97 nm at 1 month, P = 0.003; 75 nm at 5 months, P = 0.319), and thicker than that of eyes followed without surgery (97 nm vs. 66 nm, P = 0.046). MGLs after surgery remained unchanged from the preoperative MGL (all P > 0.7). CONCLUSION: Marginal entropion is associated with morphological and functional alterations of the meibomian glands. Functional improvement after entropion repair suggests that marginal entropion could cause or exacerbate MGD. Further studies are required to establish the role of entropion repair in managing MGD.

Clinical analysis of ocular adnexal mucosa-associated lymphoid tissue lymphoma with IgG4-related ophthalmic disease.

PURPOSE: To analyse the incidence and characteristics of ocular adnexal mucosa-associated lymphoid tissue lymphoma (OAML) with immunoglobulin G4 (IgG4)-related ophthalmic disease (IgG4-ROD), and to compare with IgG4-negative OAML. METHODS: We enrolled 130 patients with pathology-confirmed OAML at a single tertiary medical centre. Patients were divided into IgG4-positive and IgG4-negative groups based on the pathologic criteria for IgG4-ROD. The data were reviewed and compared between the groups. RESULTS: IgG4-positive OAML was identified in 5.4% (7/130) of OAML and 13.5% (7/52) of non-conjunctival OAML. IgG4-positive group had a higher incidence of involvement of the lacrimal gland (7/7 vs. 18/123, p = .001), extraocular muscles (3/7 vs. 10/123, p = .022) and infraorbital nerve (2/7 vs. 0/123, p < .001), and had a lower incidence of involvement of the conjunctiva (0/7 vs. 84/123; p < .001) than IgG4-negative group. IgG4-positive group had higher T and N categories of the American Joint Committee on Cancer classification (T1:T2:T3:T4 ratio of 0:6:0:1 vs. 78:32:8:5, p < .001; and ≥N1 ratio of 2/7 vs. 7/123, p = .021). There were no differences in the response rate to initial treatment (5/6 vs. 39/41, p = .343) or the relapse rate (1/6 vs. 5/41, p = 1.000) between the groups. CONCLUSION: IgG4-positive OAML showed clinical features similar to IgG4-ROD, such as predominant disease involvement of the lacrimal gland, extraocular muscles, infraorbital nerve and lymph nodes, but not the conjunctiva. However, treatment outcomes were favourable with or without background IgG4-ROD. Physicians should be aware that IgG4-ROD might undergo a malignant transformation and that thorough treatment and surveillance of IgG4-ROD are important.

Reconstruction of Large Upper Eyelid Defects Using the Reverse Hughes Flap Combined With a Sandwich Graft of an Acellular Dermal Matrix.

PURPOSE: To investigate the usefulness of the reverse Hughes flap procedure combined with a sandwich graft of an acellular dermal matrix for reconstruction of large full-thickness defects of upper eyelids after cancer excision. METHODS: Clinical data were obtained from patients who underwent upper eyelid reconstruction using a reverse Hughes flap combined with a sandwich graft of an acellular dermal matrix (AlloDerm) as a tarsal substitute. The tarsoconjunctival flap of the donor lower eyelid was mobilized to reconstruct the posterior lamella, and acellular dermal matrix was grafted onto the tarsoconjunctival flap. A skin-orbicularis muscle flap superior to the defect was advanced to cover the acellular dermal matrix graft, followed by application of lid crease formation sutures to prevent postoperative entropion. The tarsoconjunctival pedicle was divided 3-8 weeks after the surgery. RESULTS: Six patients with sebaceous carcinoma were included, and all had ≥70% full-thickness upper eyelid defects after tumor excision. After a median follow-up of 40 months (range 6-62 months), all 6 showed satisfactory functional and cosmetic outcomes. Tumor recurrence, exposure keratopathy, upper eyelid entropion, persistent use of bandage contact lenses, lower eyelid deformity, and dermal matrix-related complications were not observed by the last follow-up. CONCLUSIONS: Reverse Hughes flap combined with a sandwich graft of an acellular dermal matrix as a tarsal substitute was successful in reconstructing large upper eyelid defects. Acellular dermal matrix graft and lid crease formation sutures enhance marginal stability and prevent postoperative entropion of the reconstructed upper eyelid.

Prognostic factors for relapse and survival among patients with ocular adnexal lymphoma: validation of the eighth edition of the American Joint Committee on Cancer (AJCC) TNM classification.

BACKGROUND/AIMS: To validate the prognostic performance of the American Joint Committee on Cancer (AJCC) eighth edition classification for ocular adnexal lymphoma (OAL). METHODS: We performed a retrospective review of 140 consecutive patients treated for primary OAL between March 2010 and September 2017. Associations between T/N/M categories at presentation and disease-related outcomes, including relapse, progression-free survival (PFS) and overall survival (OS) were evaluated. RESULTS: Seventy-nine women and 61 men (median age, 52 (range 20-84) years; median follow-up, 57 (range 7-131) months) were included. Histological subtypes included mucosa-associated lymphoid tissue lymphoma (92.1%, n=129), diffuse large B-cell lymphoma (5.0%, n=7), follicular lymphoma (1.4%, n=2) and mantle cell lymphoma (1.4%, n=2). Patients with ≥T2 disease had significantly higher risks of overall relapse (unadjusted HR)=4.32, p=0.016), decreased PFS (uHR=5.19, p=0.004) and decreased OS (uHR=9.21, p=0.047). Patients with ≥N1 disease had significantly higher risks of overall relapse (uHR=9.17, p<0.001) and decreased PFS (uHR=9.24, p<0.001). M1 disease was significantly associated with higher risks of overall relapse (uHR=3.62, p=0.036), decreased PFS (uHR=5.13, p=0.001) and decreased OS (uHR=9.24, p=0.013). On considering TNM categories as continuous data, the uHRs for per level increase in T, N and M categories were 1.77, 1.83 and 2.30 for overall relapse and 1.72, 1.87 and 2.78 for decreased PFS, respectively (p<0.05 for each comparison). CONCLUSION: The T, N and M categories of the AJCC eighth edition classification have prognostic value for relapse and survival among patients with primary OAL. Particularly, nodal/metastatic involvement at presentation indicated less favourable outcome.

Alveolar soft part sarcoma of the lateral rectus muscle: Suture technique to prevent postoperative strabismus.

PURPOSE: We present a rare case of intramuscular alveolar soft part sarcoma (ASPS) of the lateral rectus (LR) muscle and the surgical technique used to maintain orthotropia after complete resection of the mass. OBSERVATIONS: A 5-year-old boy presented with progressive proptosis of the left eye due to an orbital tumor. The patient was previously diagnosed with ASPS of the left LR muscle from an incisional biopsy, and the tumor size increased despite 5 cycles of chemotherapy prior to presenting to our center. Magnetic resonance imaging showed a 28x19x15mm-sized contrast-enhancing intramuscular mass of the left LR muscle, and there was no evidence of nodal or distant metastasis. The mass was excised en bloc, along with the insertion and the posterior normal part of LR muscle. To maintain proper eye alignment after resecting LR muscle, a 4-0 Prolene® hang-back suture was placed between the scleral insertion and the periorbita of the posterior orbit and the left medial rectus muscle was injected with botulinum toxin. During the follow-up of 51 months after surgery, the patient had no evidence of recurrence or metastasis and remained orthotropic in primary gaze, with a good cosmetic result. CONCLUSIONS AND IMPORTANCE: ASPS of extraocular muscles is a rare tumor occurring mainly in children and young adults, and treatment may cause significant sequelae such as orbital exenteration, radiation-induced complications, and large-angle strabismus. Complete resection of tumor including the extraocular muscle is essential for treatment, and a subsequent reconstruction using a hang-back suture technique is useful to achieve proper eye alignment as well as a good cosmetic outcome.

Association of T and N Categories of the American Joint Commission on Cancer, 8th Edition, With Metastasis and Survival in Patients With Orbital Sarcoma.

Importance: No previous studies to date have validated the American Joint Committee on Cancer (AJCC) 8th edition of the TNM classification for orbital sarcoma. Objectives: To determine the prognostic performance of the most recent TNM classification for orbital sarcoma and to identify other prognostic factors for local recurrence, lymph node metastasis, distant metastasis, and death due to disease. Design, Setting, and Participants: This single-center retrospective cohort study included 73 consecutive patients treated for orbital sarcoma from March 1, 2003, through June 30, 2018. Data were analyzed from November 1 to December 31, 2018. Main Outcomes and Measures: T and N categories at presentation and disease-related outcomes, including local recurrence, lymph node metastasis, distant metastasis (DM), and death due to disease (DD). Results: The 73 participants included 43 men (59%), and the median age was 21 (range, 0-77) years. The common histologic types were rhabdomyosarcoma (RMS) (35 [48%]), solitary fibrous tumor/hemangiopericytoma (10 [14%]), and Ewing sarcoma (8 [11%]). The most common TNM designations were T2 N0 M0 (26 [36%]) and T4 N0 M0 (24 [33%]). T category was associated with the risk of all disease-related outcomes, including local recurrence (hazard ratio [HR] for T2 vs T4, 0.22 [95% CI, 0.06-0.81]; HR for T3 vs T4, 0.59 [95% CI, 0.13-2.65]; P = .03), lymph node metastasis by the last follow-up (T1, 1 [14%]; T2, 0; T3, 0; T4, 12 [35%]; P = .001), DM (HR for T2 vs T4, 0.29 [95% CI, 0.08-1.07]; P = .04), and DD (HR of T2 vs T4, 0.16 [95% CI, 0.04-0.73]; HR of T3 vs T4, 0.30 [95% CI, 0.04-2.34]; P = .02). Higher risk of DM and higher risk of DD were associated with disease category of at least T3 (HR for DM, 3.24 [95% CI, 0.89-11.72; P = .06]; HR for DD, 6.32 [95% CI, 1.43-27.95; P = .005]), N1 disease (HR for DM, 13.33 [95% CI, 4.07-43.65; P < .001]; HR for DD, 7.07 [95% CI, 2.45-20.44; P < .001]), tumor size larger than 3 cm (HR for DM, 2.72 [95% CI, 0.92-8.05; P = .06]; HR for DD, 5.79 [95% CI, 1.85-18.14; P < .001]), and age of patient with RMS younger than 1 year or 10 years or older (HR for DM, 6.85 [95% CI, 0.83-56.53; P = .04]; HR for DD, 7.03 [95% CI, 0.85-57.83; P = .04]). Higher risk of local recurrence was associated with disease category of at least T3 (HR for3 cm, 0.27 [95% CI, 0.09-0.77]; P = .009). Higher risk of lymph node metastasis was associated with disease category of at least T3 (odds ratio [OR], 13.33 [95% CI, 1.77-602.30]; P = .004), alveolar RMS (OR, 9.98 [95% CI, 2.13-51.55]; P = .001), and age of patient with RMS younger than 1 year or 10 years or older (OR, 9.20 [95% CI, 1.01-458.29] P = .03). Conclusions and Relevance: In patients with orbital sarcoma, T and N categories at presentation (defined by the AJCC 8th edition classification) correlate with metastasis and survival. These findings appear to support consideration of strict surveillance testing for regional nodal and systemic metastases in patients with orbital sarcoma with disease category of at least T3 and/or N1 disease.

Clinicopathologic features of biopsied lacrimal gland masses in 95 Korean patients.

PURPOSE: To investigate the clinicopathologic features of lacrimal gland masses biopsied in a tertiary referral hospital in Korea. METHODS: Records from 95 Korean patients who underwent lacrimal gland mass biopsy were retrospectively reviewed. Data included demographics, clinical presentation, imaging findings, histopathologic diagnosis, and associated systemic disease. RESULTS: The median age was 52.0 years (range, 16-76 years), and 51 patients (53.7%) were female. Thirty-three patients (34.7%) had bilateral disease. The histopathologic diagnoses were as follows: chronic dacryoadenitis (52.6%, n = 50;29 non-specific and 21 immunoglobulin G4-related disease (IgG4-RD)), lymphoproliferative disease (25.5%, n = 24; 18 lymphoma and six lymphoid hyperplasia), benign epithelial tumour (13.7%, 13 pleomorphic adenoma), malignant epithelial tumour (3.2%, three adenoid cystic carcinoma), dacryops (3.2%, n = 3), solitary fibrous tumour (1.1%, n = 1), and xanthogranulomatous inflammation (1.1%, n = 1). Patients with chronic dacryoadenitis were significantly more likely to be younger (mean 47.5 years), have bilateral involvement (52.0%), and have a longer symptom period (mean 15.6 months) than those with lymphoproliferative disease (60.0 years, 25.0%, and 6.7 months, respectively; p < 0.05, each comparison). Patients with IgG4-related dacryoadenitis were significantly more likely to have bilateral involvement (85.7%) and have associated systemic involvement (52.4%) than those with non-specific dacryoadenitis (37.9 and 0%, respectively; p < 0.05, each comparison). Sixteen patients (16.8%) had associated systemic involvement: 11 with IgG4-RD and 5 with lymphoma. CONCLUSIONS: Chronic dacryoadenitis and lymphoproliferative disease were the most common causes of lacrimal gland masses in our cohort. Younger patients with bilateral involvement and a longer symptom period were more likely to have chronic dacryoadenitis than lymphoproliferative disease. Associated systemic involvement was not rare in patients with IgG4-RD or lymphoma. Our results suggest that biopsy of chronic lacrimal gland masses should be performed for proper evaluation and management.

Predictors of Local Recurrence for Eyelid Sebaceous Carcinoma: Questionable Value of Routine Conjunctival Map Biopsies for Detection of Pagetoid Spread.

PURPOSE: To identify clinicopathologic factors associated with local recurrence of eyelid sebaceous carcinoma and determine whether routine conjunctival map biopsies are necessary to detect pagetoid spread. METHODS: The authors searched PubMed for articles on eyelid sebaceous carcinoma and pagetoid spread published in English during 1982 to 2018, and they reviewed 99 consecutive patients with eyelid sebaceous carcinoma who underwent surgical excision with frozen section control of margins performed by 1 author (BE) during 1999 to 2017. RESULTS: Local recurrence rates after surgery were 5% to 25% in the literature and 6% in the authors' cohort. Risk factors for local recurrence included T3b (>20 mm) or worse disease according to the AJCC Cancer Staging Manual, eighth edition, pagetoid spread, diffuse growth pattern, and multicentric origin. Pagetoid spread was observed in 8.3% to 70% of patients in the literature and 31% of patients in the authors' cohort. The literature review showed that surgical excision with frozen section control is the mainstay of management of eyelid sebaceous carcinoma, with topical chemotherapy and cryotherapy used in cases with pagetoid spread. The authors found no solid evidence for added value from routine 4-quadrant conjunctival map biopsies, and some studies called into question their accuracy and yield. CONCLUSIONS: In patients with eyelid sebaceous carcinoma, meticulous microscopic margin control is appropriate in all cases and particularly for tumors >20 mm and adjuvant topical chemotherapy should be considered for tumors with conjunctival pagetoid spread. Routine conjunctival map biopsies are not essential, but targeted map biopsies of areas with signs suggestive of pagetoid intraepithelial spread may be appropriate to guide future closer observation or adjuvant treatments.

Validation Study of the AJCC Cancer Staging Manual, Eighth Edition, Staging System for Eyelid and Periocular Squamous Cell Carcinoma.

Importance: To our knowledge, there are no validation studies to date of the prognostic value of the AJCC Cancer Staging Manual, eighth edition (AJCC 8), criteria for eyelid and periocular squamous cell carcinoma. Objective: To determine the association of tumor (T) category in AJCC 8 with local recurrence, nodal metastasis, distant metastasis, and disease-specific survival (DSS) for eyelid and periocular squamous cell carcinoma. Design, Setting, and Participants: In this retrospective, single-center cohort study, 109 consecutive patients with eyelid and periocular squamous cell carcinoma treated from January 1999 to April 2018 were included. Patients with secondary involvement of the periocular region were excluded. Main Outcomes and Measures: Local recurrence, nodal metastasis, distance metastasis, and DSS. Results: Of the 109 included patients, 81 (74.3%) were male, and the median (range) age was 66 (40-91) years. At presentation, 43 patients (39.4%) had recurrent tumor, 4 (3.7%) had nodal metastasis, and 1 (0.9%) had distant metastasis. The median (range) follow-up was 23 (1-161) months. During follow-up, 11 patients (10.1%) developed local recurrence, 7 (6.4%) developed nodal metastasis, 2 (1.8%) developed distant metastasis, and 9 (8.3%) died of disease. The 5-year DSS rate was 87.7% (95% CI, 79.5-96.9). Chronic immunosuppression (hazard ratio, 47.24; 95% CI, 7.33-304.30; P < .001) and presentation with recurrent squamous cell carcinoma (hazard ratio, 5.22; 95% CI, 1.12-24.31; P = .04) were associated with local recurrence during follow-up. Of the 11 patients with local recurrence during follow-up, 7 (64%) had perineural invasion. T category was associated with nodal metastasis; clinical stage of T2c or worse at presentation was associated with higher risk of nodal metastasis and death of disease but not with a higher risk of local recurrence. Distant metastasis was associated with nodal metastasis at presentation (hazard ratio, 32.50; 95% CI, 1.97-536.40; P = .02) and during follow-up. A total of 33 patients (30.3%) had different T categories depending on whether disease was staged according to the seventh or eighth edition of the AJCC Cancer Staging Manual. Compared with AJCC 7, AJCC 8 showed a better predictive value in terms of local recurrence (T3, 17% vs 14%; T4, 11% vs 16%) and DSS. Conclusions and Relevance: These findings suggest that T category in AJCC 8 is associated with nodal metastasis and DSS. Immunosuppression and presentation with recurrent disease are associated with increased risk of future local recurrence. Patients with tumors of clinical stage T2c or worse at presentation are at increased risk of nodal metastasis and worse DSS and should undergo surveillance for nodal metastasis. Future studies, ideally prospective in design, could provide greater confidence in these findings.

Intraoperative lagophthalmos formula for levator resection in congenital ptosis.

AIM: To calculate a regression formula for intraoperative lagophthalmos to determine the amount of correction in levator resection for mild to moderate congenital ptosis. METHODS: This retrospective study included 38 eyelids from 28 consecutive children with congenital ptosis with levator function of 4 mm or better who showed satisfactory surgical outcomes defined as postoperative margin reflex distance-1 (MRD1) ≥3 mm in each eye and difference in MRD1 ≤1 mm between eyes at 6 months after levator resection. We investigated whether the degree of intraoperative lagophthalmos measured by calliper correlated with the preoperative values of MRD1, levator function and age. A stepwise multiple regression analysis was performed with intraoperative lagophthalmos as the dependent variable. RESULTS: The mean intraoperative lagophthalmos was 7.4±0.9 mm (range, 6-10 mm). The intraoperative lagophthalmos was found to have a statistically significant negative correlation with preoperative MRD1 (r2 =0.55, p<0.0001) and levator function (r2 =0.53, p<0.0001), respectively. A stepwise multiple regression analysis resulted in the following regression formula: Intraoperative lagophthalmos=9.08 - 0.48×Preoperative MRD1 - 0.26×Levator function (r2 =0.60, p<0.0001). CONCLUSION: Intraoperative lagophthalmos in patients with satisfactory surgical outcome correlated negatively with both preoperative MRD1 and levator function and accounting for both variables resulted in a stronger correlation than either variable alone. Surgeons would be able to calculate the amount of surgical correction using this formula of intraoperative lagophthalmos, which could lead to a satisfactory surgical outcome in levator resection for congenital ptosis.

Prognostic factors for local recurrence, metastasis and survival for sebaceous carcinoma of the eyelid: observations in 100 patients.

BACKGROUND/AIMS: To validate the predictive value of the American Joint Committee on Cancer (AJCC) 8th-edition classification for local recurrence, metastasis and survival in patients with eyelid sebaceous carcinoma. METHODS: We performed a retrospective review of 100 consecutive patients with eyelid sebaceous carcinoma. Eyelid carcinomas were staged according to the AJCC 7th-edition and 8th-edition criteria. Associations between T and N categories and disease-related outcomes including local recurrence, lymph node metastasis, distant metastasis and survival were evaluated. RESULTS: 60 women and 40 men had a median age of 67 years (range, 41-94 years). The proportions of patients who experienced local recurrence, lymph node metastasis, distant metastasis and death from disease were 6%, 21%, 7% and 6%, respectively. Two-year and 5-year disease-specific survival (DSS) rates were 93.8% and 92.0%, respectively. There were significant correlations between (1) T2c or worse category and lymph node metastasis (p=0.04) and distant metastasis (p=0.01), (2) T3b or worse category and local recurrence (p=0.01) and death from disease (p=0.01) and (3) N1 category at presentation and distant metastasis (p<0.01) and death from disease (p<0.01). The AJCC 8th-edition classification showed a better homogeneity of the T-category distribution (p<0.01) and a slightly higher discrimination ability for lymph node metastasis (C=0.734 vs C=0.728) than the 7th-edition. CONCLUSIONS: T and N categories per AJCC 8th-edition classification are predictive of local recurrence, metastasis and DSS outcomes for eyelid sebaceous carcinoma. Surgeons should perform strict surveillance testing for nodal and systemic metastases in patients with T2c or worse T category and/or N1 disease at presentation.

Generation of customized orbital implant templates using 3-dimensional printing for orbital wall reconstruction.

OBJECTIVES: To describe and evaluate a novel surgical approach to orbital wall reconstruction that uses three-dimensionally (3D) printed templates to mold a customized orbital implant. METHODS: A review was conducted of 11 consecutive patients who underwent orbital wall reconstruction using 3D-printed customized orbital implant templates. In these procedures, the orbital implant was 3D pressed during surgery and inserted into the fracture site. The outcomes of this approach were analyzed quantitatively by measuring the orbital tissue volumes within the bony orbit using computed tomography. RESULTS: All 11 orbital wall reconstructions (6 orbital floor and 5 medial wall fractures) were successful with no post operative ophthalmic complications. Statistically significant differences were found between the preoperative and post operative orbital tissue volumes for the affected orbit (24.00 ± 1.74 vs 22.31 ± 1.90 cm3; P = 0.003). There was no statistically significant difference found between the tissue volume of the contralateral unaffected orbit and the affected orbit after reconstruction (22.01 ± 1.60 cm3 vs 22.31 ± 1.90 cm3; P = 0.182). CONCLUSION: 3D-printed customized orbital implant templates can be used to press and trim conventional implantable materials with patient-specific contours and sizes for optimal orbital wall reconstruction. It is difficult to design an orbital implant that exactly matches the shape and surface of a blowout fracture site due to the unique 3D structure of the orbit. The traditional surgical method is to visually inspect the fracture site and use eye measurements to cut a two-dimensional orbital implant that corresponds to the anatomical structure of the fracture site. However, implants that do not fit the anatomical structure of a fracture site well can cause complications such as enophthalmos, diplopia and displacement of the implant.

Non-incisional eyelid everting suture technique for treating lower lid epiblepharon.

BACKGROUND: This study investigated surgical outcomes of full-thickness eyelid everting sutures for lower lid epiblepharon and influential factors leading to surgical failure. METHODS: A retrospective review was conducted of patients with lower lid epiblepharon who underwent surgical correction using the full-thickness eyelid everting suture technique. Lower lid epiblepharon was assessed preoperatively using a morphological classification (class I-IV) according to the horizontal skin fold height and a functional classification (grade 0-3) according to the severity of keratopathy. Four stitches with 5-0 coated polyglactin 910 sutures per eyelid were made, and all procedures were conducted under local anaesthesia in an office-based setting. To assess surgical outcomes, we evaluated undercorrection at 1 month and surgical failure at 6 months after the procedure. Several factors affecting surgical failure were also investigated RESULTS: Sixty-eight eyes of 41 patients were included. There were no eyes showing an undercorrection at 1 month. Keratopathy was significantly improved at 6 months postoperation (P<0.01). All patients showed good cosmesis without undesired creation of a lower lid crease and no significant complications. Sixty-one eyes (89.7%) showed surgical success. Three patients (7.3%) required additional incisional surgery due to recurring irritation. The rate of surgical failure was significantly different between the patient groups classified by preoperative severity of keratopathy (P=0.026) and lower lid horizontal skin fold height (P<0.001). Multiple logistic regression analysis revealed that the lower lid horizontal skin fold height was significantly correlated with surgical failure (OR 18.367, P=0.002). CONCLUSION: Non-incisional eyelid everting sutures have utility for the correction of lower lid epiblepharon with advantages including its simplicity, being performed in office under local anaesthesia and minimal changes in appearance. We suggest mild to moderate epiblepharon with class I or II horizontal skin fold height and grade 1 or 2 keratopathy as the criteria for considering this suture procedure.

Clinicoserological factors associated with response to steroid treatment and recurrence in patients with IgG4-related ophthalmic disease.

PURPOSE: To investigate the factors associated with response to steroid treatment and recurrence in patients with IgG4-related ophthalmic disease (ROD). METHODS: Twenty-eight patients with biopsy-proven IgG4-ROD treated between March 2010 and January 2017 were included in this retrospective study. Clinical features, serum IgG4 levels, systemic involvement, treatments and treatment outcome, factors associated with response to treatment and recurrence were assessed. RESULT: Thirteen men and 15 women (mean age 50.8 years) were evaluated over mean follow-up period of 27.3 months. Elevated serum IgG4 levels (>1.35 g/L) and systemic disease were noted in 9 (32%) and 18 patients (64%), respectively. The lacrimal gland was involved in all patients, and 22 patients (78.6%) had bilateral involvement. Most patients (82%) responded well to systemic steroids, but 12 (43%) relapsed after the initial steroid treatment, requiring additional therapies to achieve remission. Complete response to initial steroid treatment was associated with elevated serum IgG4 levels before treatment (P=0.001) and bilateral orbital involvement (P=0.050). Recurrence was associated with elevated serum IgG4 levels before treatment (P=0.007), lower dose (P=0.057) and shorter duration of initial steroids (P=0.042). Patients with recurrence eventually required significantly more steroids than those without recurrence (P=0.011). CONCLUSIONS: Patients with IgG4-ROD responded well to systemic steroid treatment, but recurrence was common, particularly among those with elevated serum IgG4 levels and shorter duration of initial steroid treatment. Low-dose maintenance treatment with systemic steroids should be considered to avoid recurrence in patients with elevated serum IgG4 levels.