EXUDATIVE RETINAL DETACHMENT AFTER INTRAVITREAL BROLUCIZUMAB INJECTION.

PURPOSE: To report an unusual case of a patient who presented with intraocular inflammation (IOI) and an exudative retinal detachment after first brolucizumab injection and to compare this case to the existing literature. METHODS: An 80-year-old woman being treated for neovascular age-related macular degeneration presented 11 days after her first intravitreal injection of brolucizumab with IOI and an exudative retinal detachment. She was treated with systemic and topical steroids. The patient's chart was thoroughly reviewed, and notes were made on visual acuities and ocular examination findings at each relevant visit. Optical coherence tomography and ultra-widefield fluorescein angiography (UWFA) images were taken across multiple timepoints. RESULTS: The patient's IOI and exudative retinal detachment resolved three weeks after brolucizumab injection. In the literature, the incidence of IOI has been reported to be higher with brolucizumab versus aflibercept, but most of these cases were considered to be mild to moderate in severity. More recently, reports of severe IOI and retinal vasculitis associated with brolucizumab have been published in postmarketing surveillance articles. CONCLUSION: To the authors' knowledge, this is the first report of exudative retinal detachment after intravitreal brolucizumab injection. As the experience with this new drug continues to grow, reports of these events are critical to increase the understanding, so that future management strategies can be developed to improve patient outcomes.

Extensive serous ciliochoroidal detachments and macular subretinal and intraretinal fluid following laser peripheral iridotomy.

Purpose: We present multimodal imaging of an interesting case of a 78-year-old man who developed large ciliochoroidal detachments and macular subretinal and intraretinal fluid in the right eye following bilateral neodymium-doped yttrium aluminium garnet (Nd:YAG) laser peripheral iridotomies (LPIs). Observations: The ciliochoroidal detachments developed in the absence of documented post-procedure hypotony or intraocular pressure fluctuation. Ultrasound biomicroscopy (UBM) confirmed serous ciliochoroidal detachment. There are a small number of cases of ciliochoroidal detachments developing after peripheral iridotomy, but these have involved either argon laser, significant decrease in intraocular pressure, or underlying ocular conditions or structural abnormalities, such as Vogt-Koyanagi-Harada (VKH) or nanophthalmos. Conclusions: Serous ciliochoroidal detachments following the relatively non-invasive procedure of LPI are rare occurrences. We present our case in hopes of increasing awareness of this potential acute complication. We also discuss the diagnostic challenges of this unique case, the extensive work up, and current status of the patient.

Management and Complications of Dexamethasone Intravitreal Implant Migration Into the Anterior Chamber.

Purpose: To report patient demographics, the clinical course, and visual outcomes across a case series of patients who experienced dexamethasone (DEX) intravitreal implant (Ozurdex, Allergan, Inc) migration into the anterior chamber (AC), with a focus on the corneal transplantation rate. Methods: In this retrospective cross-sectional study, a chart review of all cases was performed. For numerical responses, means and SDs were calculated. Percentages and absolute numbers were used to report the proportion of patients who experienced various outcomes of interest. Results: The study comprised 32 cases. All cases occurred in pseudophakic eyes; of those, 8 (25.0%) had posterior chamber intraocular lenses in the capsular bag with no known capsular or zonular issues. The mean duration from DEX implant injection to detection of migration was 19.4 ± 14.5 days. The DEX implant was explanted in 21 patients (65.6%) and repositioned in the vitreous cavity or subconjunctival space in 6 patients (18.8%). Twelve patients (37.5%) ultimately required corneal transplantation. Conclusions: To our knowledge, this is the largest case series of DEX intravitreal implant migration into the AC compiled to date. Cases of migration occurred in individuals with no known history of significant prior zonule disruption. This potential complication should be discussed with all patients undergoing DEX implant injection, which may aid in earlier presentation and improved visual outcomes.

Familial Optic Disc Pits in 2 Father-Son Pairs: Clinical Features and Genetic Analysis.

Congenital optic disc pits (ODPs) are well-circumscribed depressions within the optic disc. Thought to arise from anomalous closure of the optic fissure during embryonic development, they are now considered to lie on a broader spectrum of congenital optic disc anomaly (CODA). An increasing number of reports describe clustering of these cases within families, suggesting that inherited genetic elements play a role in disease predisposition. Here, we highlight the clinical features of 2 sets of father-son pairs affected with ODPs and provide preliminary molecular genetic analysis. Subjects underwent complete ophthalmological examination and imaging. In addition, whole-exome sequencing was carried out following informed consent. The resulting datasets were examined for potentially causal genetic variants, both in genes already known to be linked to CODA as well as those likely to lie in the same or similar genetic pathways. In this instance, no unambiguously causal variants were identified. This case series highlights the familial inheritance of ODPs, adding to the existing body of literature supporting an underlying genetic cause for this rare clinical entity. The inclusion here of specific molecular findings raises the hope that the genetic pathophysiology underlying rare entities like ODPs might be clarified in the future by the addition of similarly molecular-documented reports.

A Case of Transient Monocular Vision Loss and Paracentral Acute Middle Maculopathy.

ABSTRACT: A 77-year-old man with multiple cerebrovascular risk factors presented with a history of transient monocular vision loss and residual paracentral visual disturbance in the right eye. Carotid ultrasounds, erythrocyte sedimentation rate, and C-reactive protein were all within normal limits. He was found to have retinal whitening within the macula in the right eye, corresponding to an area of decreased retinal perfusion on optical coherence topography (OCT)-angiography and a hyperreflective middle retina band on spectral domain-OCT. This was consistent with a diagnosis of paracentral acute middle maculopathy (PAMM). PAMM should be considered a part of the differential diagnosis in patients with focal visual disturbances, and OCT studies are recommended as part of the work up as subtle fundus findings may be missed.

Serpiginous Choroiditis Presenting in Association With Clostridium difficile Infection and Ulcerative Colitis.

Purpose: This work reports a case of serpiginous choroiditis (SC) in association with ulcerative colitis and Clostridium difficile infection. Methods: A case report is discussed. Results: A 35-year-old man with a history of ulcerative colitis and recently treated C difficile infection presented with a rapid decline in central visual acuity in both eyes. Examination findings included geographic creamy-white lesions extending from the peripapillary region in both eyes. Multimodal imaging and negative infectious workup results supported the diagnosis of SC. Visual acuity and examination findings improved after initiation of systemic prednisone therapy. Adalimumab was initiated as a steroid-sparing treatment. At the last follow-up, 5 months after the initial presentation, SC and ulcerative colitis both remain in remission. Conclusions: SC has been previously described in patients with systemic disorders, including autoimmune conditions. This patient developed SC following C difficile infection and in the context of active ulcerative colitis. To our knowledge, this is the first report of SC in association with these entities.

Ergonomics in the operating room: it doesn't hurt to think about it, but it may hurt not to!

Ergonomics has gained increasing recognition as an integral component of career longevity in ophthalmology. Residents and fellows may encounter unique ergonomic challenges when learning surgical techniques. A systematic review of the literature, specifically looking for recommendations on optimizing ergonomics in the operating room (OR) and articles that explicitly mentioned suggestions for trainees, was conducted. Of the identified 41 pieces of literature, 31 specifically mentioned ergonomics in the OR, 10 discussed vitreoretinal surgery, 2 mentioned strabismus surgery, and 2 described ergonomics in oculoplastics surgeries. Only 9 of the 41 articles explicitly mentioned either residents or fellows. Based on this review, as well as anecdotal experience, recommendations for residents, fellows, and staff ophthalmologists while working in the OR were compiled. To help offset risk for musculoskeletal injury, recommendations related to relaxation, movement, and maintenance of ergonomic focus are proposed. In addition, methods to optimize ergonomics for the patient, surgeon, surgical bed, foot pedals, surgeon's chair, and the microscope are identified. Trainees may be at particular risk for injury owing to their placement at the surgical bed, and the fact that they may be less likely to get set up ergonomically either owing to a lack of awareness and teaching on the subject, or secondary to perceived time pressures in the OR. Ergonomics should ideally be considered across all domains of life, including in the OR, clinic, and office and at home. The earlier proper positioning is adopted and becomes habitual, the less likely potentially career-threatening musculoskeletal disorders will develop.

Bilateral BrightOcular iris implants necessitating explantation and subsequent endothelial keratoplasty.

PURPOSE: To demonstrate the dangers associated with the BrightOcular iris implant, a model that had initially been touted as safer than its predecessors. OBSERVATIONS: A 41-year-old male presented with decreased vision in both eyes, approximately two years following bilateral BrightOcular cosmetic iris implantation performed in Mexico. On initial consultation, he was found to have bilateral corneal decompensation with stromal edema and a significantly reduced endothelial cell count (ECC). On follow up 5 weeks later, his vision and corneal edema had further detriorated. In the following month, he underwent explantation of the cosmetic iris implants in both eyes. Significant corneal edema persisted in the right eye several months post-operatively, to the point of necessitating endothelial keratoplasty. CONCLUSIONS AND IMPORTANCE: Despite numerous reports in the literature of the significant ocular complications that can arise secondary to cosmetic iris implantation, individuals continue to willingly undergo this surgery. Our intention with presenting this case to the ophthalmologic community is two-fold: to highlight the ongoing clinical risk that BrightOcular devices pose, despite being marketed as safer than the older NewColourIris models, and to stress the urgency with which cosmetic iris implants should be removed from the eye.

Optimizing Glycemic Control in Adults With Type 1 or Type 2 Diabetes Attending a Multidisciplinary Foot Clinic.

OBJECTIVES: To determine the impact of a diabetes nurse educator (DNE) on glycemic control in a multidisciplinary diabetes foot (MDF) clinic. METHODS: A prospective cohort trial to measure the impact of a DNE on glycemic control was conducted in an MDF clinic. Change in glycated hemoglobin (A1C) levels over time was measured against the percentage of patient visits (PPVs) accompanied by a glucose meter and/or diary. RESULTS: Increasing PPVs were significantly associated with decline in A1C levels in females. Every 10% increase in PPVs resulted in a 0.18% decrease in A1C levels (p<0.0001). To achieve a clinically important decrease of 1% in A1C levels, a 56% increase in PPVs was required. Increased A1C levels were significantly associated with higher baseline A1C levels (p<0.001) and increased hospital days for foot complications (p<0.0052). CONCLUSIONS: Regular, face-to-face contact with a DNE in an MDF clinic has a positive impact on glycemic control in females.

Nonclassical resident macrophages are important determinants in the development of myocardial fibrosis.

Macrophages are increasingly recognized as a potential therapeutic target in myocardial fibrosis via interactions with fibroblasts. We have characterized macrophage depletion and inhibition of nonclassical macrophage migration, in addition to direct interactions between nonclassical macrophages and fibroblasts in angiotensin II (AngII)-mediated, hypertensive myocardial fibrosis. Macrophage depletion was achieved by daily i.v. clodronate liposomes (-1 day to +3 days) during AngII infusion. Cx3cr1(-/-) mice were used to inhibit nonclassical macrophage migration. Macrophage phenotype (F4/80, CD11b, Ly6C) was characterized by immunofluorescence and flow cytometry. Collagen was assessed by Sirius Red/Fast Green. Quantitative real-time RT-PCR was performed for transcript levels. AngII/wild-type (WT) mice displayed significant infiltrate and fibrosis compared with saline/WT, which was virtually ablated by clodronate liposomes independent of hypertension. In vitro data supported M2 macrophages promoting fibroblast differentiation and collagen production. AngII/Cx3cr1(-/-) mice, however, significantly increased macrophage infiltrate and fibrosis relative to AngII/WT. AngII/Cx3cr1(-/-) mice also showed an M1 phenotypic shift relative to WT mice in, which the predominant phenotype was Ly6C(low), CD206(+) (M2). Myocardial IL-1ß was significantly up-regulated, whereas transforming growth factor ß down-regulated with this M1 shift. We demonstrated that infiltrating macrophages are critical to AngII-mediated myocardial fibrosis by preventing the development of fibrosis after liposomal depletion of circulating monocytes. Our findings also suggest that some macrophages, namely M2, may confer a protective myocardial environment that may prevent excessive tissue injury.

Antibody therapy can enhance AngiotensinII-induced myocardial fibrosis.

BACKGROUND: Myocardial fibrosis is a pathological process that is characterized by disrupted regulation of extracellular matrix proteins resulting in permanent scarring of the heart tissue and eventual diastolic heart failure. Pro-fibrotic molecules including transforming growth factor-ß and connective tissue growth factor are expressed early in the AngiotensinII (AngII)-induced and other models of myocardial fibrosis. As such, antibody-based therapies against these and other targets are currently under development. RESULTS: In the present study, C57Bl/6 mice were subcutaneously implanted with a mini-osmotic pump containing either AngII (2.0 µg/kg/min) or saline control for 3 days in combination with mIgG (1 mg/kg/d) injected through the tail vein. Fibrosis was assessed after picosirius red staining of myocardial cross-sections and was significantly increased after AngII exposure compared to saline control (11.37 ± 1.41%, 4.94 ± 1.15%; P <0.05). Non-specific mIgG treatment (1 mg/kg/d) significantly increased the amount of fibrosis (26.34 ± 3.03%; P <0.01). However, when AngII exposed animals were treated with a Fab fragment of the mIgG or mIgM, this exacerbation of fibrosis was no longer observed (14.49 ± 2.23%; not significantly different from AngII alone). CONCLUSIONS: These data suggest that myocardial fibrosis was increased by the addition of exogenous non-specific antibodies in an Fc-mediated manner. These findings could have substantial impact on the future experimental design of antibody-based therapeutics.