Vision loss with pembrolizumab treatment: A report of two cases.

BACKGROUND: Vision loss and other ocular toxicities are rare, but detrimental, side effects of immune checkpoint inhibitors. Herein, we report two patients who developed vision loss while on pembrolizumab treatment. CASES PRESENTATION: Case 1 - A 58-year-old man was started on pembrolizumab for advanced melanoma. He was tolerating the treatment well. After receiving 14 cycles of pembrolizumab, he developed acute bilateral vision loss and occipital headaches. An emergent ophthalmologic evaluation revealed bilateral shallow choroidal effusion with bilateral focal exudative retinal detachment. After excluding other possible etiologies, inflammatory process secondary to pembrolizumab was suspected. Pembrolizumab was stopped, and the patient was started on a course of systemic and topical steroids. His vision improved within days and he recovered completely within two months. Calculated Naranjo Nomogram score was 7 indicating a "probable" correlation; Case 2 - A 57-year-old man with stage IIIC melanoma was started on adjuvant pembrolizumab. After a few weeks of treatments, he reported minor bilateral vision changes that progressively worsened over a period of six months. An ophthalmologic evaluation revealed bilateral posterior uveitis with right optic disc edema. Pembrolizumab-related inflammatory changes were suspected, and he was started on systemic and topical steroids. His symptoms improved within a few weeks and steroids were tapered. He was re-challenged with pembrolizumab and his symptoms quickly re-occurred. Pembrolizumab was stopped indefinitely and the patient again treated with systemic and topical steroids. His symptoms resolved and his vision returned to baseline within two months. The Naranjo Nomogram score was 9 indicating a "definite" correlation. CONCLUSIONS: Vision loss is a serious complication that may occur at any point during treatment with PD-1 inhibitors. Vision loss is very distressing to the patients and their families. It is prudent for practitioners to recognize early vision abnormalities in patients receiving PD-1 antagonists to prevent permanent vision loss.

Bisphosphonate-induced orbital inflammation in a patient on chronic immunosuppressive therapy.

BACKGROUND: To report a case of orbital inflammation after bisphosphonate infusion in a patient who was already receiving immunosuppressive therapy. CASE PRESENTATION: A 56-year-old woman presented to the ophthalmology clinic with acute onset of right eye pain 24 h after receiving her first Zolendronic acid infusion. She has a past medical history of chronic inflammatory demyelinating polyneuropathy, Sjogren's syndrome, and systemic lupus erythematosus that have been controlled with immunosuppressive therapy for three years. Clinical ophthalmic exam and MRI studies were significant for right orbital inflammation. The patient was started on oral prednisone with rapid resolution of symptoms. CONCLUSIONS: This is the first case report of a patient receiving chronic immunosuppressive therapy to develop orbital inflammation after Zoledronic acid infusion. In addition, it demonstrates that corticosteroids can be an effective first line therapy in treating orbital inflammation in similar patients. Physicians should be aware of this rare but serious potential side effect of bisphosphonates, and have bisphosphonate-related orbital inflammation on their differential for proper initiation of treatment.

Deep lateral wall orbital decompression following strabismus surgery in patients with Type II ophthalmic Graves' disease.

PURPOSE: Surgical management of ophthalmic Graves' disease traditionally involves, in order, orbital decompression, followed by strabismus surgery and eyelid surgery. Nunery et al. previously described two distinct sub-types of patients with ophthalmic Graves' disease; Type I patients exhibit no restrictive myopathy (no diplopia) as opposed to Type II patients who do exhibit restrictive myopathy (diplopia) and are far more likely to develop new-onset worsening diplopia following medial wall and floor decompression. Strabismus surgery involving extra-ocular muscle recession has, in turn, been shown to potentially worsen proptosis. Our experience with Type II patients who have already undergone medial wall and floor decompression and strabismus surgery found, when additional decompression is necessary, deep lateral wall decompression (DLWD) appears to have a low rate of post-operative primary-gaze diplopia. METHODS: A case series of four Type II ophthalmic Graves' disease patients, all of whom had already undergone decompression and strabismus surgery, and went on to develop worsening proptosis or optic nerve compression necessitating further decompression thereafter. In all cases, patients were treated with DLWD. Institutional Review Board approval was granted by the University of Kansas. RESULTS: None of the four patients treated with this approach developed recurrent primary-gaze diplopia or required strabismus surgery following DLWD. CONCLUSIONS: While we still prefer to perform medial wall and floor decompression as the initial treatment for ophthalmic Graves' disease, for proptosis following consecutive strabismus surgery, DLWD appears to be effective with a low rate of recurrent primary-gaze diplopia.

A case series of dural venous sinus stenting in idiopathic intracranial hypertension: association of outcomes with optical coherence tomography.

Purpose/Aim: Pseudotumor cerebri or idiopathic intracranial hypertension (IIH) is characterized by increased intracranial pressure of unknown etiology. A subset of patients has shown benefit from endovascular dural venous sinus stenting (DVSS). We sought to identify a population of IIH patients who underwent DVSS to assess outcomes. MATERIALS AND METHODS: A retrospective study was performed to identify IIH patients with dural sinus stenosis treated with DVSS. Outcome measures included dural sinus pressure gradients, peripapillary retinal nerve fiber layer (RNFL) thickness using optical coherence tomography and improvement in symptoms. RESULTS: Seventeen patients underwent DVSS. Average pre- and post-intervention pressure gradients were 23.06 and 1.18 mmHg, respectively (p < 0.0001). Sixteen (94%) noted improvement in headache, fourteen (82%) had visual improvement and all (100%) patients had improved main symptom. Of 11 patients with optical coherence tomography, 8 showed decreased RNFL thickness and 3 remained stable; furthermore, these 11 patients had improved vision with improved papilledema in 8, lack of pre-existing papilledema in 2 and stable, mild edema in 1 patient. CONCLUSIONS: Our series of patients with dural sinus stenosis demonstrated improvement in vision and reduction in RNFL thickness. DVSS appears to be a useful treatment for IIH patients with dural sinus stenosis.

Farris-Tang retractor in optic nerve sheath decompression surgery.

PURPOSE: Our purpose is to introduce the use of the Farris-Tang retractor in optic nerve sheath decompression surgery. METHODS: The procedure of optic nerve sheath fenestration was reviewed at our tertiary care teaching hospital, including the use of the Farris-Tang retractor. RESULTS: Pseudotumor cerebri is a syndrome of increased intracranial pressure without a clear cause. Surgical treatment can be effective in cases in which medical therapy has failed and disc swelling with visual field loss progresses. Optic nerve sheath decompression surgery (ONDS) involves cutting slits or windows in the optic nerve sheath to allow cerebrospinal fluid to escape, reducing the pressure around the optic nerve. We introduce the Farris-Tang retractor, a retractor that allows for excellent visualization of the optic nerve sheath during this surgery, facilitating the fenestration of the sheath and visualization of the subsequent cerebrospinal fluid egress. Utilizing a medial conjunctival approach, the Farris-Tang retractor allows for easy retraction of the medial orbital tissue and reduces the incidence of orbital fat protrusion through Tenon's capsule. CONCLUSION: The Farris-Tang retractor allows safe, easy, and effective access to the optic nerve with good visualization in optic nerve sheath decompression surgery. This, in turn, allows for greater surgical efficiency and positive patient outcomes.

Relationship Between Age, Gender, and Race in Patients Presenting With Myasthenia Gravis With Only Ocular Manifestations.

BACKGROUND: The demographic associations among patients presenting with myasthenia gravis with only ocular manifestations (OMG) is not clear. METHODS: In this 5-center case series, we collected the race, gender, and age at diagnosis of patients diagnosed with myasthenia gravis who had no signs or symptoms of generalized myasthenia gravis (GMG). An a priori sample size calculation determined that 140 patients were required to accept that there was a ≤10-year difference in mean age (equivalence testing: power 90%, α = 0.05). Robust Bayesian analysis and linear regression were applied to evaluate whether age differed by gender or race. RESULTS: Of 433 patients included, 258 (60%) were men. Mean age among men was 57 years (SD = 19) and 52 years (SD = 21) among women. The 95% credible interval (CI) (Bayesian equivalent of confidence interval) was 0.8-8.7 years for mean age, and there was a 99.6% probability that the mean difference in age between sexes was <10 years. Race was documented in 376 (68 [18%] non-Caucasian). Caucasians were 17.3 years older than non-Caucasians at diagnosis (95% CI, 12.2-22.3 y; P < 0.001) controlling for gender. There was no additive interaction of gender and race (P = 0.74). There was a bimodal distribution for women peaking around 30 and 60 years. Men had a left skewed unimodal age distribution peaking at age 70. CONCLUSIONS: The distribution of age at presentation in patients with OMG is different between men and women, similar to GMG. Non-Caucasian patients tend to develop OMG at a younger age.

Cytokine profiles in clinical subtypes of ophthalmic Graves' disease.

PURPOSE: To examine the association of cytokines in the two clinical subtypes of ophthalmic Graves' disease by comparing cytokine expression in the fat and ethmoid tissue of type I and type II patients. METHODS: Patients needing orbital decompression or eyelid surgery were identified and enrolled into a prospective study. Patients were assigned to the type I or type II subclassification, based on the presence of diplopia. Orbital fat, sinus tissue or muscle removed during surgery was evaluated. The mRNA expression profiles of Th1 cytokines (TNF-alpha/beta, IFN-gamma, IL-2) and Th2 cytokines (IL-4, IL-5, IL-6, IL-10) were analyzed using real time PCR. RESULTS: 30 patients were enrolled in the study: 5 type I (80% female), 14 type II (71% female) and 11 controls (73% female). There were 14 decompressions (3 type I and 11 type II), 17 lid procedures (2 type I, 4 type II and 11 controls) and 10 ethmoidectomies (3 type I and 7 type II). The average ages were 45, 56 and 66 in the type I, type II and control groups, respectively. There was more TNF-alpha (p value 0.009) and IL-6 (p value 0.04) in ethmoid sinus cells of type II patients compared to ethmoid sinus cells of type I patients and a trend of higher expression of all cytokines in type II patients. CONCLUSIONS: There is a trend towards greater mRNA expression of both Th1 and Th2 cytokines in both orbital fat and ethmoidal sinus tissue of type II patients compared to type I patients.