RESUMEN
PURPOSE: To present four female-to-male (FTM) transgender patients on testosterone therapy diagnosed with idiopathic intracranial hypertension (IIH). METHODS: The authors report 4 consecutive FTM transgender patients on exogenous testosterone diagnosed with IIH at a single institution. RESULTS: Patient 1 presented with progressive blurred vision and a central scotoma 10 weeks after starting testosterone cypionate injections for hormonal gender transition. Bilateral grade 5 papilledema was present; the patient underwent bilateral optic nerve sheath fenestration with improved vision and resolution of edema. Patient 2 presented with transient vision loss, pulsatile tinnitus, and blurred vision 13 months after starting testosterone cypionate injections. The patient had grade 4 and 3 disc edema of the right and left eyes, respectively. Patient 3 presented with headaches and pulsatile tinnitus and was on testosterone injections at an unknown dose. The examination revealed grade 1 and 2 disc edema of the right and left eyes, respectively. Patient 4 presented with decreased vision, transient visual obscurations, and daily migraines while using topical testosterone gel every other day. Color vision was reduced, and lumbar puncture revealed elevated intracranial pressure. All patients had neuroimaging findings consistent with increased intracranial pressure. CONCLUSIONS: Testosterone therapy plays an essential role in FTM hormonal transitioning and may play a role in IIH. Patients undergoing testosterone therapy for gender transition should be informed of the possibility of developing IIH while on treatment, with obesity possibly increasing this risk. Comprehensive eye examinations should be considered in these patients before initiating hormone therapy.
Asunto(s)
Papiledema , Seudotumor Cerebral , Acúfeno , Personas Transgénero , Humanos , Masculino , Femenino , Seudotumor Cerebral/inducido químicamente , Seudotumor Cerebral/diagnóstico , Papiledema/inducido químicamente , Papiledema/diagnóstico , Trastornos de la Visión/diagnóstico , Testosterona/efectos adversos , EdemaRESUMEN
The authors present a case of a non-traumatic, spontaneous subperiosteal orbital hematoma in a woman with a history of chronic pansinusitis and absence of midline nasal cavity structures due to chronic inhalational cocaine use. The patient underwent left orbitotomy and drainage of the lesion, showing mostly blood with a small amount of purulence that grew methicillin-resistant Staphylococcus aureus when cultured. The patient received 4 weeks of intravenous antibiotics in addition to functional endoscopic sinus surgery. At 1 month after surgery, her vision had returned to baseline, and proptosis was resolved. Fewer than 20 cases of subperiosteal orbital hematomas associated with chronic sinusitis have been reported. To the authors' knowledge, this is the first reported case of a subperiosteal orbital hematoma associated with cocaine-induced midline destructive lesions. Patient consent to obtain photographs was obtained and archived. All collection and evaluation of patient health information were compliant with the Health Insurance Portability and Accountability Act, and this report adheres to the Declaration of Helsinki.
Asunto(s)
Cocaína , Exoftalmia , Staphylococcus aureus Resistente a Meticilina , Enfermedades Orbitales , Sinusitis , Humanos , Femenino , Enfermedades Orbitales/inducido químicamente , Enfermedades Orbitales/diagnóstico , Cocaína/efectos adversos , Hematoma/complicaciones , Hematoma/cirugía , Sinusitis/complicacionesRESUMEN
PURPOSE: To assess the sensitivity and specificity of superior visual field tests administered in virtual reality (VR) with eye tracking (VR-ET) and without eye tracking (VR 0 ) for the fulfillment of insurance coverage criteria for functional upper eyelid surgery as compared with standard automated perimetry (SAP). METHODS: This prospective cross-sectional study included 78 eyes from 41 patients with ptosis, brow ptosis, and dermatochalasis undergoing functional upper eyelid surgery evaluation. Participants underwent serial superior visual field tests using SAP and VR 0 or VR-ET in randomized order. Fulfillment of insurance coverage criteria for blepharoplasty was defined as a 30% increase in the grid seen from the untaped to the taped state. The main outcome measure was the sensitivity and specificity of VR 0 , VR-ET, and overall VR in meeting insurance coverage criteria as compared with SAP. RESULTS: VR had a sensitivity of 84.1% and specificity of 67.6%, with no significant difference between VR 0 and VR-ET. SAP agreed on insurance coverage criteria fulfillment with VR 0 in 28 (71.8%) eyes and with VR-ET in 32 (82.1%) eyes. Insurance coverage criteria fulfillment rates varied significantly by diagnosis on SAP ( p = 0.012) but not VR ( p = 0.059). CONCLUSIONS: VR may be an alternative to SAP for functional upper eyelid surgery evaluation. Future studies are needed to determine differences in patient satisfaction, testing and waiting time, and test-retest reliability between VR and SAP.
Asunto(s)
Pruebas del Campo Visual , Campos Visuales , Humanos , Proyectos Piloto , Estudios Prospectivos , Reproducibilidad de los Resultados , Tecnología de Seguimiento Ocular , Estudios Transversales , Párpados/cirugíaRESUMEN
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.
Asunto(s)
Procedimientos de Cirugía Plástica , Vejiga Urinaria , Animales , Humanos , Evisceración Orbitaria , Procedimientos de Cirugía Plástica/métodos , Estudios Retrospectivos , Porcinos , Vejiga Urinaria/cirugíaRESUMEN
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% versus 8% for Con versus 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 (<1%). There was no significant difference in these complications between the Con and Coff cohorts. CONCLUSIONS: Complications in both groups were minimal, similar to prior studies, and there was no difference between the 2 cohorts. While it has been suggested that buried conjunctiva may result in increased complication rates, the author's findings suggest that removing the tarsal conjunctiva is a superfluous step in the LTS surgery and does not affect complication rates.
Asunto(s)
Blefaroplastia , Ectropión , Blefaroplastia/efectos adversos , Conjuntiva/cirugía , Ectropión/cirugía , Párpados/cirugía , Humanos , Complicaciones Posoperatorias/cirugía , Estudios Retrospectivos , Técnicas de SuturaRESUMEN
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.
Asunto(s)
Carcinoma Basocelular , Porocarcinoma Ecrino , Neoplasias Cutáneas , Neoplasias de las Glándulas Sudoríparas , Anciano de 80 o más Años , Carcinoma Basocelular/cirugía , Porocarcinoma Ecrino/diagnóstico , Porocarcinoma Ecrino/cirugía , Párpados , Femenino , Humanos , Recurrencia Local de Neoplasia , Neoplasias de las Glándulas Sudoríparas/diagnóstico , Neoplasias de las Glándulas Sudoríparas/cirugíaRESUMEN
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 improve ments in diplopia, enophthalmos, and extraocular motility with a low incidence of postoperative complications or revisional surgery.
Asunto(s)
Enoftalmia , Fracturas Orbitales , Implantes Orbitales , Procedimientos de Cirugía Plástica , Adulto , Enoftalmia/etiología , Enoftalmia/cirugía , Femenino , Humanos , Masculino , Persona de Mediana Edad , Órbita/cirugía , Fracturas Orbitales/cirugía , Polietileno , Porosidad , Estudios Retrospectivos , Titanio , Resultado del TratamientoRESUMEN
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.
Asunto(s)
Mitocondrias/efectos de los fármacos , Oligopéptidos/farmacología , Traumatismos del Nervio Óptico/tratamiento farmacológico , Células Ganglionares de la Retina/patología , Factor de Necrosis Tumoral alfa/antagonistas & inhibidores , Enfermedad Aguda , Animales , Supervivencia Celular , Humanos , Mitocondrias/metabolismo , Traumatismos del Nervio Óptico/metabolismo , Traumatismos del Nervio Óptico/patología , Células Ganglionares de la Retina/efectos de los fármacos , Células Ganglionares de la Retina/metabolismo , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
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.
Asunto(s)
Placas Óseas , Nistagmo Patológico/cirugía , Músculos Oculomotores/fisiopatología , Órbita/cirugía , Titanio , Visión Binocular/fisiología , Movimientos Oculares , Femenino , Estudios de Seguimiento , Humanos , Persona de Mediana Edad , Nistagmo Patológico/fisiopatología , Procedimientos Quirúrgicos Oftalmológicos , Diseño de Prótesis , Factores de TiempoRESUMEN
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.
Asunto(s)
Técnicas de Apoyo para la Decisión , Enfermedades del Aparato Lagrimal/diagnóstico , Lágrimas/metabolismo , Parpadeo/fisiología , Enfermedades de la Conjuntiva/metabolismo , Párpados/fisiología , Humanos , Enfermedades del Aparato Lagrimal/metabolismoRESUMEN
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.
Asunto(s)
Carcinoma Adenoide Quístico , Neoplasias del Ojo , Neoplasias de Cabeza y Cuello , Enfermedades del Aparato Lagrimal , Aparato Lagrimal , Carcinoma Adenoide Quístico/tratamiento farmacológico , Procedimientos Quirúrgicos de Citorreducción , Neoplasias del Ojo/tratamiento farmacológico , Neoplasias del Ojo/patología , Estudios de Seguimiento , Humanos , Aparato Lagrimal/patología , Enfermedades del Aparato Lagrimal/tratamiento farmacológico , Enfermedades del Aparato Lagrimal/patología , Márgenes de Escisión , Terapia Neoadyuvante , Recurrencia Local de Neoplasia , Estudios RetrospectivosAsunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Quimioterapia del Cáncer por Perfusión Regional/efectos adversos , Enfermedades de la Coroides/inducido químicamente , Enfermedades en Gemelos , Enoftalmia/inducido químicamente , Neoplasias de la Retina/tratamiento farmacológico , Retinoblastoma/tratamiento farmacológico , Antineoplásicos Alquilantes/administración & dosificación , Antineoplásicos Alquilantes/efectos adversos , Atrofia , Coroides/patología , Enfermedades de la Coroides/diagnóstico , Terapia Combinada , Enoftalmia/diagnóstico , Femenino , Angiografía con Fluoresceína , Humanos , Lactante , Coagulación con Láser , Imagen por Resonancia Magnética , Melfalán/administración & dosificación , Melfalán/efectos adversos , Arteria Oftálmica , Escleritis/inducido químicamente , Escleritis/diagnóstico , Inhibidores de Topoisomerasa I/administración & dosificación , Inhibidores de Topoisomerasa I/efectos adversos , Topotecan/administración & dosificación , Topotecan/efectos adversos , Gemelos MonocigóticosRESUMEN
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.
Asunto(s)
Dirofilaria/aislamiento & purificación , Dirofilariasis/cirugía , Cuerpos Extraños en el Ojo/cirugía , Infecciones Parasitarias del Ojo/cirugía , Loa/aislamiento & purificación , Loiasis/cirugía , Adulto , Animales , Enfermedades de la Conjuntiva/diagnóstico , Enfermedades de la Conjuntiva/parasitología , Enfermedades de la Conjuntiva/cirugía , Dirofilariasis/diagnóstico , Dirofilariasis/parasitología , Combinación de Medicamentos , Epinefrina/administración & dosificación , Cuerpos Extraños en el Ojo/diagnóstico , Cuerpos Extraños en el Ojo/parasitología , Infecciones Parasitarias del Ojo/diagnóstico , Infecciones Parasitarias del Ojo/parasitología , Enfermedades de los Párpados/diagnóstico , Enfermedades de los Párpados/parasitología , Enfermedades de los Párpados/cirugía , Femenino , Humanos , Lidocaína/administración & dosificación , Loiasis/diagnóstico , Loiasis/parasitología , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Enfermedades Cutáneas Parasitarias/diagnóstico , Enfermedades Cutáneas Parasitarias/parasitología , Enfermedades Cutáneas Parasitarias/cirugíaRESUMEN
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.
Asunto(s)
Modelos Animales de Enfermedad , Etanercept/uso terapéutico , Inmunosupresores/uso terapéutico , Traumatismos del Nervio Óptico/tratamiento farmacológico , Células Ganglionares de la Retina/efectos de los fármacos , Factor de Necrosis Tumoral alfa/antagonistas & inhibidores , Enfermedad Aguda , Animales , Supervivencia Celular/fisiología , Electrorretinografía , Regulación de la Expresión Génica/fisiología , Inmunohistoquímica , Inyecciones Subcutáneas , Ratones , Ratones Endogámicos C57BL , Compresión Nerviosa , Neuroprotección/efectos de los fármacos , Traumatismos del Nervio Óptico/metabolismo , Traumatismos del Nervio Óptico/patología , Reacción en Cadena en Tiempo Real de la Polimerasa , Células Ganglionares de la Retina/metabolismo , Factor de Necrosis Tumoral alfa/genética , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
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.
Asunto(s)
Traumatismos del Nervio Óptico , Nervio Óptico , Ondas Ultrasónicas/efectos adversos , Animales , Modelos Animales de Enfermedad , Humanos , Ratones , Nervio Óptico/metabolismo , Nervio Óptico/patología , Nervio Óptico/fisiopatología , Traumatismos del Nervio Óptico/metabolismo , Traumatismos del Nervio Óptico/patología , Traumatismos del Nervio Óptico/fisiopatologíaRESUMEN
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.
Asunto(s)
Acomodación Ocular/efectos de los fármacos , Anticuerpos Monoclonales Humanizados/efectos adversos , Antineoplásicos/efectos adversos , Neoplasias Encefálicas/tratamiento farmacológico , Gangliósidos/inmunología , Midriasis/inducido químicamente , Neuroblastoma/tratamiento farmacológico , Anticuerpos Monoclonales Humanizados/administración & dosificación , Antineoplásicos/administración & dosificación , Niño , Relación Dosis-Respuesta a Droga , Femenino , Humanos , Incidencia , Infusiones Intravenosas , Masculino , Midriasis/diagnóstico , Midriasis/fisiopatología , Recurrencia Local de Neoplasia , Estudios Retrospectivos , Factores de RiesgoRESUMEN
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.
Asunto(s)
Antineoplásicos Alquilantes/toxicidad , Carboplatino/toxicidad , Endotelio Vascular/ultraestructura , Infusiones Intraarteriales/efectos adversos , Leucostasis/patología , Melfalán/toxicidad , Arteria Oftálmica/efectos de los fármacos , Oclusión de la Arteria Retiniana/patología , Animales , Arteriolas , Biomarcadores/metabolismo , Coroiditis/inducido químicamente , Coroiditis/patología , Endotelio Vascular/efectos de los fármacos , Endotelio Vascular/metabolismo , Técnicas para Inmunoenzimas , Molécula 1 de Adhesión Intercelular/metabolismo , Interleucina-8/metabolismo , Leucostasis/inducido químicamente , Macaca mulatta , Masculino , Fibras Nerviosas/efectos de los fármacos , Fibras Nerviosas/patología , Arteria Oftálmica/ultraestructura , Oclusión de la Arteria Retiniana/inducido químicamente , Células Ganglionares de la Retina/efectos de los fármacos , Células Ganglionares de la Retina/patologíaRESUMEN
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.