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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.Non-randomized, retrospective, interventional case series.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.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.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.

PURPOSE: The lateral tarsal strip (LTS) procedure is commonly used to correct eyelid malposition. When performing LTS, some surgeons elect to remove conjunctiva from the tarsal strip, while others do not. It has been hypothesized that without conjunctival stripping, the buried conjunctival tissue can cause complications such as inclusion cysts and granulomas. However, there is limited data comparing LTS cases with and without conjunctiva removal. The authors sought to evaluate whether conjunctival stripping had any impact on complication rates with LTS. METHODS: LTS operations for ectropion correction were retrospectively reviewed and were separated into 2 cohorts, Con (conjunctiva not removed) or Coff (conjunctival removed). Charts were reviewed for outcomes and complications including inclusion cyst formation, granuloma formation, wound dehiscence, infection and focal rim tenderness. RESULTS: The complication rate was 10% vs 8% for Con vs Coff respectively (p=0.54). The common complications of LTS surgery were granuloma (4%), wound dehiscence (3%), focal rim tenderness (3%), and infection requiring antibiotics (

Reconstruction options after orbital exenteration can be challenging, time-consuming, and require intensive postoperative care. Engineered dermal acellular matrices offer a quick and easy option for wound healing that has proven to be successful in various settings. Specifically, the porcine urinary bladder matrix has demonstrated success in periocular and orbital wound healing. This report describes a pediatric patient who underwent repair with porcine urinary bladder matrix after orbital exenteration for recurrent alveolar rhabdomyosarcoma. The patient did not require any additional reconstructive procedures. To our knowledge, this is the youngest patient to receive a porcine urinary bladder matrix after exenteration.

Purpose Complex bony orbital defects are reconstructively challenging due to loss of intraoperative anatomical landmarks and adjacent support. Presized and precontoured porous polyethylene-titanium implants (Medpor Titan 3D Orbital Floor Implant) are designed to reestablish normal orbital floor and medial wall anatomy and are modeled after anatomically averaged orbits. This is the first study to report clinical outcomes with this implant. Methods This retrospective case series reviewed clinical data and outcomes for patients undergoing orbital reconstruction with a presized and precontoured porous polyethylene-titanium orbital implant from January 2016 to June 2018. Results A total of 34 orbits of 33 patients were identified (mean age: 43 ± 16 years, 70% men). Most bony defects were a result of trauma and included large orbital floor deformities (100%), medial wall defects (74%), disrupted inferomedial struts (68%), and broken posterior ledges (82%). Symptomatic diplopia (73%) and enophthalmos (89%, mean: 3.7 ± 2.1 mm) were common preoperatively. Many cases were revisions (44%). Mean follow up was 7.8 ± 6.7 months. All patients had improved globe positioning, enophthalmos, and hypoglobus. Seven patients had persistent postoperative diplopia: 6 responded to prism therapy and 1 required strabismus surgery. One patient required retrobulbar hematoma drainage and 1 patient required implant explantation due to chronic infection. Conclusions Commercially available presized and precon-toured porous polyethylene-titanium implants are useful for complex orbital bony defects and can achieve functional improvements in diplopia, enophthalmos, and extraocular motility with a low incidence of postoperative complications or revisional surgery.

Traumatic optic neuropathy (TON) can occur following blunt trauma to the orbit and can lead to permanent vision loss. In this study, we investigated the effectiveness of elamipretide (MTP-131), a small mitochondrially-targeted tetrapeptide, in conjunction with etanercept, a tumor necrosis factor (TNF) inhibitor, as neuroprotective agents of retinal ganglion cells (RGCs) after optic nerve trauma with sonication-induced TON (SI-TON) in mice. Treatment with intravitreal MTP-131 and subcutaneous etanercept and MTP-131 showed a 21% increase (p 0.01) in RGC survival rate compared to PBS-treated control eyes. Subcutaneous etanercept and MTP-131 had an 11% increase (p 0.05) in RGC survival compared to controls. Subcutaneous etanercept only group showed 20% increase (p 0.01) in RGC survival compared to controls, while subcutaneous MTP-131 alone showed a 17% increase (p 0.01). Surprisingly, we did not observe a synergistic effect between the two drugs in the group receiving both etanercept and MTP-131. One possible explanation for the absence of a synergistic effect is that MTP-131 and etanercept may be acting on different portions of the same pathway.

An 81-year-old woman presented with a progressively enlarging indurated, firm lesion encompassing one-third of the left upper eyelid. Four years prior, a similar lesion at that same site had been excised and diagnosed as a basal cell carcinoma. The patient underwent a full-thickness excision of the lesion with frozen section, cryotherapy, and reconstruction. A free tarsal graft and hard palate composite graft was used to reconstruct the posterior lamella. A Mustarde myocutaneous rotational flap was used to reconstruct the anterior lamella. Histopathology illustrated nests of pleomorphic basophilic cells with varying mitotic activity and immunohistochemical staining consistent with eccrine porocarcinoma. This case highlights similarities in the presentation and appearance of basal cell carcinoma and periorbital eccrine porocarcinoma. It is possible that there was de novo development of the 2 tumors on the eyelid or recurrence of a misdiagnosed eccrine porocarcinoma. Eccrine porocarcinomas are rare malignant sweat gland tumors associated with a risk of recurrence after excision and metastasis.

This section will discuss the role of enucleation and exenteration in the setting of the two most common primary intraocular tumors – retinoblastoma and uveal melanoma. The treatment of these tumors is complex and usually requires a multidisciplinary approach, which is beyond the scope of this chapter. Eye removal (enucleation or exenteration) is only one option of many for these patients and is the main focus of this chapter. Evisceration should never be performed if an eye has or is suspected of having an intraocular tumor.

Purpose To determine the effectiveness of etanercept, a tumor necrosis factor (TNF) inhibitor, in conferring neuroprotection to retinal ganglion cells (RGCs) and improving visual outcomes after optic nerve trauma with either optic nerve crush (ONC) or sonication-induced traumatic optic neuropathy (SI-TON) in mice. Methods Mouse optic nerves were unilaterally subjected to ONC (n = 20) or SI-TON (n = 20). TNF expression was evaluated by using immunohistochemistry and quantitative RT-PCR (qRT-PCR) in optic nerves harvested 6 and 24 hours post ONC (n = 10) and SI-TON (n = 10). Mice in each injury group received daily subcutaneous injections of either etanercept (10 mg/kg of body weight; five mice) or vehicle (five mice) for 7 days. Pattern electroretinograms were performed on all mice at 1 and 2 weeks after injury. ONC mice were killed at 2 weeks after injury, while SI-TON mice were euthanized at 4 weeks after injury. Whole retina flat-mounts were used for RGC quantification. Results Immunohistochemistry and qRT-PCR showed upregulation of TNF protein and gene expression within 24 hours after injury. In both models, etanercept use immediately following optic nerve injury led to higher RGC survival when compared to controls, which was comparable between the two models (24.23% in ONC versus 20.42% in SI-TON). In both models, 1 and 2 weeks post injury, mice treated with etanercept had significantly higher a-wave amplitudes than untreated injured controls. Conclusions Treatment with etanercept significantly reduced retinal damage and improved visual function in both animal models of TON. These findings suggest that reducing TNF activity in injured optic nerves constitutes an effective therapeutic approach in an acute setting.

In the United States and other developed nations, more patients with retinoblastoma will die from non-ocular second malignant neoplasms than from their primary intraocular tumor. There is an increased lifetime risk of the development of second malignant neoplasms in survivors of heritable retinoblastoma compared with their nonheritable counterparts. Radiation increases the risk of second malignant neoplasms and should be avoided when possible. All patients at risk must be educated to remain vigilant for future signs or symptoms of malignancies and counseled to avoid exposure to other mutagens. The prognosis for patients with second malignant neoplasms is guarded and underscores the importance of counseling patients with the heritable form of the disease.

A 49-year-old woman with debilitating nystagmus and oscillopsia failed conservative therapy. A titanium T-plate was anchored to the lateral orbital rim and cantilevered into the orbit where it was secured to the inferior rectus muscle tendon with a suture. After the procedure was performed on both eyes, the patient had significant decreases in the amplitudes of her nystagmus and oscillopsia, thereby improving her daily function. She had sustained duration of effect through 7 years of follow up. This novel surgical technique holds promise in the treatment of acquired nystagmus and debilitating oscillopsia for which conventional therapy may be ineffective. The case report is in compliance with the Health Insurance Portability and Accountability Act.

Purpose To determine the incidence of and factors associated with the development of mydriasis and impaired accommodation in patients with refractory or recurrent neuroblastoma receiving the anti-GD2 antibody hu14.18K322A. Methods The medical records of eligible patients with refractory or recurrent neuroblastoma who received escalating doses of hu14.18K322A, ranging from 2 to 70 mg/m 2 /dose for 4 consecutive days every 28 days, were retrospectively reviewed to identify ocular abnormalities arising during the treatment period. Results A total of 38 patients (median age, 7 years; 23 males) were included. All patients underwent comprehensive eye examinations prior to each course of therapy. Mydriasis was seen in 13 patients (34%), and impaired accommodation was seen in 9 (24%), indicating a dose-related effect between hu14.18K322A and both mydriasis ( P = 0.021) and impaired accommodation ( P = 0.029). Age and sex were not associated with ocular abnormalities. Ocular symptoms resolved in the majority of patients after the drug was discontinued. Conclusions Side effects of mydriasis and impaired accommodation have a dose-dependent relationship with hu14.18K322A. These side effects do not warrant discontinuation of treatment, as they usually resolve after completion of therapy. Management of ocular side effects should focus on treating symptoms with manifest refraction, bifocals, or tinted spectacles.

Traumatic optic neuropathy (TON) is a devastating cause of permanent visual loss following blunt injury to the head. Animal models for TON exist, but most fail to recapitulate the clinical scenario of closed head indirect trauma to the nerve and subsequent neurodegeneration. Thus, we developed a clinically-relevant animal model for TON using a novel ultrasonic pulse injury modality (sonication-induced TON; SI-TON). To trigger TON, a microtip probe sonifier was placed on the supraorbital ridge directly above the entrance of the optic nerve into the bony canal. An ultrasonic pulse was then delivered to the optic nerve. After injury, the number of RGCs in the retina as well as visual function measured by PERG steadily decreased over a two-week period. In the optic nerve, pro-inflammatory markers were upregulated within 6 hours following injury. Immunohistochemistry showed activation of microglia and infiltration of CD45-positive leukocytes in the optic nerve and initiation of a gliotic response. The SI-TON model is capable of delivering a non-contact concussive injury to the optic nerve and induce TON in mice. Thus, our data indicate that the SI-TON model reliably recapitulates the pathophysiology and progressive neurodegeneration seen in the human manifestation.

Endophthalmitis is an intraocular infection that can lead to significant decrease in vision. Severe infections with virulent organisms or untreated infections can result in panophthalmitis, an infection that extends outside the globe and results in intraorbital inflammation and orbital cellulitis. Complete loss of vision can occur in these cases as the eye becomes filled with purulence. Inadequate treatment can lead to intracranial extension of the infections, meningitis, cavernous sinus thrombosis, and even death. In these severe cases, medical treatment alone is often inadequate, and surgical intervention with either evisceration or enucleation is necessary.

Lacrimal Gland Adenoid Cystic Carcinoma (LGACC) is a rare but devastating cancer with a high modality rate. In 75% of cases, perineural migration of LGACC can spread intracranially and invade into orbital bone. Currently, patients with LGACC are treated with chemotherapy and exenteration. Despite these interventions, LGACC has a high frequency of local recurrence and distant metastasis. Only 50% of patients survive to 5 years after diagnosis, and just 25% survive to 15 years. To overcome the difficulties in preventing cancer recurrence and metastasis, better treatments for LGACC are urgently needed. To better understand the pathophysiology of LGACC, we have reviewed the recent literature on clinical and research advances in LGACC. In this chapter, we mainly focus on the genetic and mechanistic studies on important tumorigenic signaling molecules such as MYB, Notch and FGFR. MYB is a proto-oncogene and key regulator of stem cells. In LGACC, MYB-NFIB fusion transcripts are formed by chromatin rearrangements in the MYB locus, leading to the overexpression of MYB. Mutations in the PEST domain and heterodimerization domain of Notch cause accumulation of the Notch intracellular domain (NICD), which is the biologically active form of Notch. The fibroblast growth factor receptor pathway also plays an important role during lacrimal gland development. Growing evidence indicates that FGFR is an effective biological target in other types of ACC. Small molecule inhibitors for FGFR may therefore shed new light on the treatment of LGACC.

Purpose Evaluation of the tearing patient is often distilled to a search for ocular surface problems causing reflex hypersecretion versus lacrimal drainage problems. The literature does not typically emphasize conditions affecting the function of the tear distribution system, but neglect of these important factors can lead to suboptimal treatment outcomes. The intent of this review is to provide a systemic evaluation of frequently overlooked conditions that can influence the distribution system and to offer a mnemonic to ensure an orderly sequence of inspection during clinical examination. Methods Review of clinical literature and experience from 1957 to 2014. Results Tearing complaints attributable to problems with the distribution system can be evaluated, classified, and managed according to the mnemonic BLICK, which stands for Blink dynamics, Lid malposition, Imbrication, Conjunctivochalasis, and Kissing puncta. Conclusion The BLICK mnemonic is a useful adjunct to the workup of epiphora.

Purpose To describe 3 patients with chronic mucopurulent conjunctivitis found to have an unrecognized sequestration of bacteria within tarsoconjunctival crypts of the upper eyelid. Design Review of 3 noncomparative cases. Methods settings: Institutional. study population: Three consecutive patients with tarsoconjunctival crypts. intervention procedure: Marsupialization of the individual crypts. main outcome measures: Resolution of chronic discharge and resolution of signs and symptoms. Results One patient with Stevens-Johnson syndrome and 2 patients with floppy eyelids had chronic mucopurulent conjunctivitis that was refractory to multiple medical and surgical interventions. Retention of a yellowish coagulum within the fistulous tracts of the tarsal conjunctiva was the site of pathologic features in all patients. The diagnosis was confirmed by squeezing out of the coagulum from the fistulous tracts by pinching the eyelid horizontally. Pseudomonas aeruginosa was isolated in 1 patient and Staphylococcus aureus was isolated in the other 2 patients. A Bowman probe could be passed through the fistulous opening to unveil the full extent of the conjunctival tunnels on the epitarsal surface. Each tract was marsupialized, and no relapse was found during a follow-up period of 12 to 96 months. Conclusions Patients with chronic, relapsing, purulent conjunctivitis should have their upper eyelid everted to search for tarsoconjunctival crypts as the source of bacteria-laden coagulum. The formation of the crypts is likely the result of tarsal conjunctiva trauma with lamellar de-epithelialization, followed by re-epithelialization to form an epithelialized tunnel as a potential space for harboring bacteria. Marsupialization of the crypts obliterates the potential space and is curative.

In the management of retinoblastoma, it is important to remember that there is an entire patient to treat – not just an intraocular tumor. Children with heritable retinoblastoma who have a germ-line mutation in RB1 have an increased risk of developing a second malignancy. All familial cases, all bilateral cases, and approximately 15 % of unilateral cases fall into this category. The most common secondary malignancies are sarcomas, melanoma, and brain tumors. The association of retinoblastoma and an intracranial neuroblastic malignancy, known as “trilateral retinoblastoma,” most often involves the pineal gland (“pineoblastoma/pinealoblastoma”) but may also involve parasellar and suprasellar regions ( Chap. 20) [1–3]. The increased risk of developing second, non-ocular malignancies for survivors of heritable retinoblastoma is estimated to be 20 times higher than the general population [4].

PURPOSE Superselective intraophthalmic artery chemotherapy (SSIOAC) is being used for treatment of retinoblastoma; however, the hemodynamic consequences and toxicities are not fully known. We developed a nonhuman primate (NHP) model of SSIOAC and reported our clinical observations. For validation, we compared ophthalmic artery (OA) diameters between NHPs and children (

PURPOSE To describe the clinical presentation of migratory nematodes and to outline a simple strategy to ensure capture. METHODS Retrospective case series. RESULTS Two consecutive patients with suspected migratory nematodes were treated promptly by strategic placement of a pharmacological barrier in the forniceal conjunctiva using 1% lidocaine with epinephrine to block the routes of retreat and to immobilize the worms for controlled retrieval. Two live nematode worms, one subcutaneous dirofilaria and one subconjunctival Loa loa, were successfully removed. CONCLUSIONS A sense of urgency is conveyed to isolate the migratory worm while it is still visible and residing in a location for easy surgical removal. The retreat of the worm to the deeper, inaccessible orbit is prevented by strategic placement of a perimeter of anesthetic.

Importance We describe the histopathologic findings in a nonhuman primate (NHP) model of superselective intraophthalmic artery chemotherapy (SSIOAC), detailing ocular and orbital vascular adverse effects. Objective To further document, using comprehensive ocular and orbital histopathology, previously reported toxic effects observed with real-time ophthalmoscopy during SSIOAC in a NHP model. Design Comparative interventional case series. Setting Preclinical trial approved under the guidelines of the Institutional Animal Care and Utilization committee. Participants Six adult male rhesus macaques ( Macacca mulatta ). Interventions The right eye of each NHP was treated with 3 cycles of SSIOAC using either melphalan (5 mg/30 mL) or carboplatin (30 mg/30 mL). Both eyes in each animal were enucleated 6 hours after the final procedure, before euthanasia and formalin perfusion of the NHP; we then performed orbital dissection of the arterial vasculature and optic nerves. Main Outcome Measures Histopathologic examination of the eyes, optic nerves, and orbital vessels of the 6 treated NHPs. Results We found leukostasis with retinal arteriole occlusion in all treated eyes. Retinal endothelial cells stained positive for 2 inflammatory markers, intercellular adhesion molecule 1 and interleukin 8. Transmission electron microscopy revealed occlusion of the retinal vessels with ultrastructural changes in the endothelial cells and surrounding pericytes. Additional findings included nerve fiber layer infarcts, central retinal artery thrombosis, hypertrophy and occlusion of choroidal arteries with disruption of the internal elastic lamina, patchy choroidal inflammation, and birefringent intravascular foreign bodies. Orbital findings included ophthalmic artery and central retinal artery wall dissection, fracturing of the internal elastic lamina, intimal hyperplasia, and eyelid vessel damage. Optic nerves displayed hemorrhage, leukostasis, and foreign body crystallization. Control eyes, optic nerves, and orbital vessels were normal. Conclusions and Relevance Histopathologic examination of our nonhuman primate model for SSIOAC revealed significant toxic effects in the ocular and orbital vasculature. These findings substantiate previous observations with real-time retinal imaging and parallel reported vascular toxic effects in children with retinoblastoma treated with SSIOAC.