Ophthalmic immune-related adverse events associated with immune checkpoint inhibitors.

Purpose: To investigate the incidence of immune-related adverse events (irAEs) of immune checkpoint inhibitor (ICI) therapy and to report the clinical features, management, and outcomes of ophthalmic irAEs. Methods: We retrospectively reviewed the medical records of patients who received ICI therapy from January 2016 to September 2022 at Peking Union Medical College Hospital and analyzed the incidence of systemic and ophthalmic adverse effects of this therapy. Results: Of 962 patients, 248 (25.8%) experienced irAEs. The first-year incidences of total irAEs and ophthalmic irAEs were 23.5% and 1.1%. The most common ICI received by the patients was pembrolizumab (373; 38.8%). Nearly half of the patients (477; 49.6%) had lung cancer. Combination therapy was associated with an increased incidence of irAEs without statistical significance. Patients with lung cancer presented with an increased incidence of total irAEs (p = 0.003) and ophthalmic irAEs (p = 0.032). Eleven patients had ophthalmic manifestations, including ophthalmoplegia (6/11), conjunctivitis (3/11), reactive cutaneous capillary endothelial proliferation (RCCEP) (1/11), and orbital inflammation (1/11). Eight patients had concomitant extra-ophthalmic irAEs. Furthermore, ICIs were discontinued in nine patients, and most ophthalmic manifestations were well controlled with topical and systemic steroids. Ten patients were treated with intravenous or oral steroids. However, cancer progression occurred in five out of eleven patients after the interruption of ICIs. Conclusion: IrAEs are correlated with ICI regimens and underlying neoplasia. In our Chinese cohort, patients have a higher risk of ophthalmoplegia than uveitis. Early recognition and multidisciplinary consultation are crucial for optimal treatment of ophthalmic irAEs.

Ocular Immune-Related Adverse Events Associated With Immune Checkpoint Inhibitors in Lung Cancer.

Immune checkpoint inhibitors (ICIs) are novel immunotherapy-based drugs that have become increasingly popular in the treatment of lung cancer. Researchers have recognized ocular immune-related adverse events (irAEs) secondary to ICIs because of their vision-threatening characteristics. However, they are incompletely characterized and no studies have reported the ICI-related ocular irAEs in lung cancer. Therefore, we aimed to comprehensively illustrate the clinical characteristics, contributory factors, diagnosis, and management of ICI-related ocular irAEs in lung cancer, based on previously reported 79 patients. Ophthalmoplegia (40.51%), uveitis (20.25%), and dry eye (17.72%) were the most common ICI-related ocular irAEs in lung cancer. Ptosis was the most common (36.71%) and the highest mortality (23.33%) of ophthalmoplegia. Patients in Asia and patients who underwent combination therapy with programmed cell death-1 and cytotoxic T-lymphocyte-associated antigen 4 inhibitors demonstrated significantly higher frequency of ophthalmoplegia than other ocular irAEs. Most ICI-related ophthalmoplegia and uveitis in lung cancer were observed in the first 10 weeks following the initiation of ICIs. Furthermore, the onset time of dry eye and other ocular irAEs was much longer. In addition, 92.31% of the patients with ocular irAEs other than ophthalmoplegia could be remised. In conclusion, ocular irAEs secondary to ICIs in lung cancer are non-negligible, particularly ophthalmoplegia. Ethnicity and the type of ICIs play important roles in the distribution of ocular irAEs. ICI-related ophthalmoplegia in lung cancer presented with early onset and worse prognosis features, thus necessitating further attention.

Visual loss from dermal fillers.

BACKGROUND: An increasing number of people are undergoing non-surgical aesthetic procedures, especially injections of botulinum toxin and dermal fillers. While toxin injections have lower rates of complications, profound and serious consequences can arise with the use of dermal fillers. CASE: A 29-year-old woman presented to the eye casualty department with sudden visual loss, ptosis and ophthalmoplegia after having had non-surgical rhinoplasty in a beauty salon in West London. The filler was administered by a healthcare professional not registered with the General Medical Council (GMC) or similar governing body. DISCUSSION: Despite prompt measures on arrival at our service, the symptoms of visual loss, ptosis and ophthalmoplegia persisted. Attempts from the patient and medical services to report the incident (to trading standards and the police) were to no avail. CONCLUSION: This case highlights the poor treatment response to filler-related ophthalmic complications. It is also evident that in the United Kingdom, there appears to be poor regulation in the use of these products, a lack of clear guidelines for the management of their complications and finally no recourse for patients to challenge practitioners who lack medical registration and are not held accountable.

Immune checkpoint inhibitors (ICIs)-related ocular myositis.

We present extensive clinical, serological, morphological and muscle imaging data of a 66-year-old man with isolated bilateral ptosis and external ophthalmoplegia secondary to Immune checkpoint inhibitors (Pembrolizumab). He had elevated CK level (>5000 UI/L). No facial, bulbar, proximal, distal or axial muscular weakness was observed. Electromyography (EMG) showed myopathic pattern, with spontaneous activity. Myositis specific antibodies and anti-striational antibodies were negative. Cardiac and respiratory functions were preserved. Skeletal muscle MRI was unremarkable, whereas extraocular muscles revealed bilateral hyperintensities in inferior rectus, medial rectus and superior oblique muscles in both T1 and STIR sequences, with mild muscle atrophy. Muscle biopsy showed endomysial inflammatory infiltrates, MHC-1 expression was observed in clusters of non-necrotic cells. CD56 positive cells were observed in perifascicular regions. Patient discontinued Pembrolizumab and received corticosteroid treatment with progressive clinical improvement and CK normalization. Our findings support this clinical entity, suggesting that isolated ocular myositis represents a subgroup of generalised myositis with predominant ocular symptoms.

Isolated Ophthalmoplegia Following Filler Injections to the Upper Face.

Ophthalmoplegia following cosmetic facial filler injections is a rare but serious complication. The authors report 2 cases of ophthalmoplegia following filler injection. In the first case, a 54-year-old female presented with acute onset headache, vomiting, and diplopia during malar and temporal injection of hyaluronic acid. In the second case, a 37-year-old female presented with binocular diplopia that developed following injection of an unknown filler to the upper face. Neither of the 2 patients had skin necrosis or ocular abnormalities other than motility deficits. To the authors' knowledge, there have been no other cases of isolated ophthalmoplegia without evidence of other ocular injuries following facial filler.

Surgical outcomes of strabismus after iatrogenic ophthalmic artery occlusion caused by cosmetic filler injections.

BACKGROUND: To investigate the surgical outcomes of strabismus related to iatrogenic occlusion of the ophthalmic artery and its branches from cosmetic facial filler injection. METHODS: A retrospective study was performed on 6 patients who underwent strabismus surgery among 23 patients who had suffered occlusion of the ophthalmic artery and its branches after cosmetic facial filler injection. Initial, preoperative and final ocular motility examinations, the type of surgery and surgical outcomes were evaluated. RESULTS: At initial presentation, visual acuity was no light perception in 5 patients and hand motion in one patient. Five out of 6 patients showed initial ophthalmoplegia. Among these 5 patients, eye motility fully recovered in 3 patients although sensory strabismus developed during follow-up, while the remaining 2 patients had persistent ocular motility limitations. Strabismus surgery was performed at 2.2 ± 1.5 years after iatrogenic ophthalmic artery occlusion. Preoperatively, 5 of the 6 patients showed exotropia, and one patient had esotropia. Vertical deviation was found in 3 out of 6 patients in addition to the horizontal deviation. Successful outcome was achieved only in the 4 patients without persistent ophthalmoplegia after 1.4 ± 1.0 years from surgery. The other two patients with persistent ocular motility limitations failed to achieve successful alignment after surgery, and one patient eventually underwent evisceration due to phthisis bulbi. CONCLUSIONS: In our study, surgical outcomes of strabismus caused by cosmetic facial filler injection were successful only in patients without persistent ophthalmoplegia at the time of surgery.

Neuropatía óptica compresiva secundaria a reacción alérgica a hialuronidasa / Compressive optic neuropathy secondary to an allergic reaction to hyaluronidase

Una mujer de 58 años presentó quemosis intensa y oftalmoparesia en el ojo izquierdo 8 h después de cirugía de catarata no complicada bajo anestesia subtenoniana. Tras tratamiento corticoideo y antihistamínico, se observó recuperación de la motilidad extrínseca pero se apreciaron un edema de papila no hemorrágico y un defecto concéntrico de campo visual. El caso evolucionó a atrofia papilar con agudeza visual central preservada pero con una contracción significativa del campo visual. El estudio etiológico reveló una alergia a la hialuronidasa, usada como adyuvante a la anestesia. Esta complicación debe ser diagnosticada y tratada precozmente, puesto que el edema de los tejidos orbitarios puede dañar el nervio óptico

A 58 year-old woman presented with severe chemosis and ophthalmoparesis on her left eye 8 hours after uncomplicated cataract surgery under sub-tenon anaesthesia. Recovery of extrinsic motility was observed after corticosteroid and antihistamine treatment, but a non-haemorrhagic papillary oedema and a concentric defect of visual field were found. It progressed to papillary atrophy with preserved central vision, but with a significant visual field constriction. The aetiological study revealed an allergy to hyaluronidase that was used as adjuvant to the anaesthesia. This complication needs to be promptly diagnosed and treated, as the swelling of the orbital tissues can cause damage to the optic nerve

Compressive optic neuropathy secondary to an allergic reaction to hyaluronidase. / Neuropatía óptica compresiva secundaria a reacción alérgica a hialuronidasa.

A 58 year-old woman presented with severe chemosis and ophthalmoparesis on her left eye 8hours after uncomplicated cataract surgery under sub-tenon anaesthesia. Recovery of extrinsic motility was observed after corticosteroid and antihistamine treatment, but a non-haemorrhagic papillary oedema and a concentric defect of visual field were found. It progressed to papillary atrophy with preserved central vision, but with a significant visual field constriction. The aetiological study revealed an allergy to hyaluronidase that was used as adjuvant to the anaesthesia. This complication needs to be promptly diagnosed and treated, as the swelling of the orbital tissues can cause damage to the optic nerve.

Natural Course of Ophthalmoplegia after Iatrogenic Ophthalmic Artery Occlusion Caused by Cosmetic Filler Injections.

BACKGROUND: Besides the devastating complication of blindness, paralysis of the eye muscles, namely ophthalmoplegia, may occur after cosmetic facial filler injection. However, little is known of the clinical characteristics and prognosis of such complications. This study was performed to investigate the natural course of ophthalmoplegia and development of sensory strabismus secondary to blindness after iatrogenic occlusion of the ophthalmic artery and its branches resulting from cosmetic facial filler injection. METHODS: A retrospective study of 21 patients with occlusion of the ophthalmic artery and its branches after cosmetic facial filler injection was performed. The clinical characteristics and prognosis of ophthalmoplegia after cosmetic filler injection were evaluated. At the final examination, development of sensory strabismus defined as deviation of the eye secondary to unilateral vision loss was evaluated. RESULTS: At initial presentation, ophthalmoplegia was found in 15 of 21 patients (71 percent) and was significantly associated with the presence of anterior segment ischemia (p = 0.017). Among patients with ophthalmoplegia at initial presentation, ocular motility recovered completely in 77 percent and incomplete recovery was found in 23 percent. At the final examination, sensory strabismus developed in 42 percent after an average follow-up of 2.5 years. CONCLUSIONS: Ophthalmoplegia frequently occurs after iatrogenic occlusion of the ophthalmic artery and its branches caused by cosmetic facial filler injection. Ocular motility recovers spontaneously in most patients. However, as most patients are blind, sensory strabismus may develop in nearly half of patients during follow-up that requires strabismus surgery. CLINICAL QUESTION/LEVEL OF EVIDENCE: Risk, IV.

Pembrolizumab-induced Ocular Myasthenia Gravis with Anti-titin Antibody and Necrotizing Myopathy.

A 73-year-old man developed diplopia after the administration of pembrolizumab for lung adenocarcinoma. He had ptosis and external ophthalmoplegia without general muscle weakness. Serum CK levels were elevated. Although autoantibodies to acetylcholine receptor and muscle-specific kinase, the edrophonium test, and the repetitive nerve stimulation test were all negative, anti-titin autoantibody was positive, leading to the diagnosis of myasthenia gravis (MG). Muscle pathology showed necrotizing myopathy with tubular aggregates. Unlike previously reported cases of pembrolizumab-associated MG, the present case showed ocular MG. This is the first case of pembrolizumab-associated MG with anti-titin antibody, as well as the first case with tubular aggregates.

A Case of Hyaluronic Acid Induced Blindness With Ophthalmoplegia and Ptosis.

Hyaluronic acid injection can lead to skin necrosis, visual loss, and other complications. The blindness with ophthalmoplegia and ptosis is a rare, but terrible and devastating complication. The disfigured appearance usually has significant impact on patient's social life. There is no standard treatment. A patient with hyaluronic acid induced blindness, ophthalmoplegia, and ptosis is reported. Six days after the onset, peribulbar/retrobulbar injections of high dosage hyaluronidase were performed. The orbital edema and ptosis immediately improved. The ophthalmoplegia and ptosis improved significantly within a month and resolved completely within 3 months, although the right vision remained blind. Peribulbar/retrobulbar injection of hyaluronidase is a potential rescue therapy for the hyaluronic acid induced ophthalmoplegia and ptosis.

Complete ophthalmoplegia in Ipilmumab and Nivolumab combination treatment for metastatic melanoma.

Ipilimumab and Nivolumab are novel monoclonal antibodies that have recently been used successfully for treatment of metastatic melanoma. Ipilimumab is a human monoclonal antibody against Cytotoxic T Lymphocyte Antigen 4 (CTLA4) receptor, which suppresses T-cell proliferation and stimulates an inflammatory response against cancer cells. Nivolumab is an IgG4 monoclonal antibody against the cytotoxic T lymphocyte associated programmed death 1 receptor (PD-1). Ipilimumab and Nivolumab combination treatment has been shown to induce remission and prolong survival in patients with metastatic melanoma. The side effect profile of these medications has not been well studied. One entity of the side effects reported in the literature is immune-related adverse events (irAEs). There have been few case reports where these events were serious and irreversible. In this case report, we describe a fatal and severe diffuse panmyositis that involved the cardiac, respiratory, and extraocular muscles in a patient with metastatic melanoma secondary to combination treatment with Ipilimumab/Nivolumab.

Paralysis of the orbicularis muscle of the eye using botulinum toxin type A in the treatment for dry eye.

PURPOSE: To evaluate the efficacy of botulinum toxin type A injection to cause orbicularis eyelid muscle paralysis to improve dry eye signs and symptoms. METHODS: A prospective, randomized, comparative eye-to-eye and interventional study was performed. Patients with dry eye symptoms and positive fluorescein corneal staining were included. Randomly one eyelid received a subcutaneous injection of botulinum toxin in the medial orbicularis muscle portion of the lower eyelid, and the other eye received placebo. The subjective evaluation was achieved with a questionnaire assessing symptoms, quality of vision and ocular comfort level. The objective evaluation included the measurement of the tear film break-up time (TBUT), Schirmer's test and corneal and conjunctival staining. RESULTS: Twenty patients were included with a mean age of 59.5 years. Two weeks after the botulinum toxin injection, all patients showed a decrease in the horizontal movement of the lower eyelid when blinking. The eyes in the active treatment group showed better scores compared with the sham group in four symptoms 4 weeks after the treatment. The TBUT was higher at 1 and 3 months in the active treatment group. The corneal and conjunctival staining were significantly lower in the active treatment group at 1 and 3 months, and the Schirmer's test showed better measurements in the same group at 2 weeks, 1 month and 3 months. There were no adverse events reported. CONCLUSIONS: The injection of botulinum toxin A in the medial part of the lower eyelid is an effective and safe procedure that temporally improves some of the signs and symptoms of patients with dry eye.

Parálisis de la convergencia secundaria a amoxicilina / Convergence palsy secondary to amoxicillin

CASO CLÍNICO: Presentamos el caso de un varón de 11 años, con diplopía aguda en la visión cercana, secundario a una parálisis de la convergencia transitoria, posiblemente relacionada con la toma de amoxicilina. DISCUSIÓN: La parálisis de la convergencia es un trastorno poco frecuente. Repasamos las causas que la pueden producir, e identificamos a la amoxicilina como agente etiológico. Es el primer caso comunicado (AU)

CASE REPORT: We present the case of an 11-year-old boy with acute diplopia in near vision secondary to transient convergence palsy, possibly in relation to amoxicillin. DISCUSSION: Convergence palsy is an uncommon eye disorder. The causes are reviewed, and amoxicilin is identified as presumptive etiologic agent. This is the first case reported

Retinal Branch Artery Embolization Following Hyaluronic Acid Injection: A Case Report.

Injection of hyaluronic acid (HA) filler is a common aesthetic procedure. Impairment of vision, although rare, is a devastating complication of this procedure, which may not be reversible. We report on a patient who experienced visual acuity impairment and ischemic oculomotor nerve palsy after injection of HA into the nasal dorsum. In this case, clinical signs improved within 14 days of treatment. We also provide a review of the mechanism, clinical features, risk factors, and prevention and treatment strategies relating to embolization of ocular circulation after injection of HA. Vision loss is a rare but devastating complication of injection of hyaluronic acid (HA) in the face. Visual acuity seldom recovers completely. We report on a 22-year-old Asian woman who experienced obstruction of a branch of the retinal artery after injection of HA to augment her nose. The patient's visual acuity declined shortly after the procedure, and ophthalmoplegia occurred. Combination treatment was administered to restore the perfusion and oxygen supply to the retina and optic nerve. Within 14 days of rigorous treatment, the patient experienced improvement in visual acuity, extraocular movement, and visual field defects. LEVEL OF EVIDENCE 5: Risk.

Vincristine-Induced Neuropathy Presenting as Ptosis and Ophthalmoplegia in a 2-Year-Old Boy.

Vincristine is used in the treatment of leukemias, solid tumors, and lymphomas. A case of a 2-year-old boy undergoing treatment for leukemia who developed sudden onset bilateral ptosis and ophthalmoplegia along with generalized neuropathy due to vincristine's neurotoxic effects is presented. He was successfully treated with pyridoxine and pyridostigmine. The possible mechanisms of action and the treatment for vincristine-induced neuropathy are discussed. Prompt treatment and close follow-up is needed, especially in children because prolonged ptosis and motility restriction may have a profound effect on a child's visual function.

[Ophthalmic complications and local anesthesia. Pathophysiology and types of eye complications after intraoral dental anesthesia, and clinical recommendations]. / Ophthalmologische Komplikationen und Lokalanästhesie. Pathophysiologie und Formen der Augenkomplikationen nach intraoraler zahnärztlicher Lokalanästhesie und klinische Empfehlungen.

The present article reviews the different types of ophthalmologic complications following administration of intraoral local anesthesia. Since the first report by Brain in 1936, case reports about that topic have been published regularly in the literature. However, clinical studies evaluating the incidence of ophthalmologic complications after intraoral local anesthesia are rarely available. Previous data point to a frequency ranging from 0.03% to 0.13%. The most frequently described ophthalmologic complications include diplopia (double vision), ptosis (drooping of upper eyelid), and mydriasis (dilatation of pupil). Disorders that rather affect periorbital structures than the eye directly include facial paralysis and periorbital blanching (angiospasm). Diverse pathophysiologic mechanisms and causes have been reported in the literature, with the inadvertent intravascular administration of the local anesthetic considered the primary reason. The agent as well as the vasopressor is transported retrogradely via arteries or veins to the orbit or to periorbital structures (such as the cavernous sinus) with subsequent anesthesia of nerves and paralysis of muscles distant from the oral cavity. In general the ophthalmologic complications begin shortly after administration of the local anesthesia, and disappear once the local anesthesia has subsided.

Thyroid-like ophthalmopathy in a euthyroid patient receiving Ipilimumab.

A 68-year-old lady with metastatic malignant melanoma was treated with Ipilimumab. She presented to Eye Casualty unable to move her eyes. Physical examination confirmed ophthalmoplegia and identified proptosis bilaterally. Radiological imaging showed bilateral enlargement of all the extra-ocular muscles suggestive of thyroid eye disease. Laboratory investigations found this patient to be euthyroid. A diagnosis of thyroid-like orbitopathy secondary to Ipilimumab therapy was made. Thyroid function tests should be performed for all patients prior to their commencement of Ipilimumab. Thyroid-like eye disease may develop in patients treated with Ipilimumab even if they remain euthyroid.