2020

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E J-Y, Mihailovic A, Kuo P-L, West SK, Friedman DS, Gitlin LN, Li T, Schrack JA, Ramulu PY. Characterizing the Impact of Fear of Falling on Activity and Falls in Older Adults with Glaucoma. J Am Geriatr Soc 2020;68(8):1847-1851.Abstract
OBJECTIVE: Fear of falling (FoF) may alter mobility in older adults, especially among those with visual impairment. Using a longitudinal prospective cohort of older glaucoma patients, we investigated whether and how FoF is associated with future falls and physical activity. DESIGN: Prospective observational cohort study. SETTING: Hospital-based single-center recruitment. PARTICIPANTS: Individuals with glaucoma or suspected glaucoma. MEASUREMENTS: FoF was measured annually over a 3-year period using the University of Illinois at Chicago FoF Questionnaire, with lower Rasch-analyzed FoF scores (in logit units) indicating less fear. Participants recorded falls prospectively over the 3-year period using monthly mail-in calendars. Daily steps were collected annually over 7 days using an accelerometer. Visual field (VF) sensitivity was derived by combining sensitivities from monocular VF results. Participants completed questionnaires to determine other demographic/health characteristics. Multivariate random effects models evaluated within-participant changes in fall rates and physical activity across study years. RESULTS: At lower FoF levels (FoF≤0), each one-unit worsening in FoF score across study years was associated with 2.73 times higher odds of reporting at least one fall in the next year (95% confidence interval [CI] = 1.55-4.81) but was not associated with average daily steps (P = .44). Similar results were seen when fall rates were normalized by number of steps taken (P = .97). At higher FoF levels (FoF > 0), inter-year changes in FoF scores were not significantly associated with reporting a fall in the following year (P = .78) but were associated with 407 fewer average daily steps per one-unit change in FoF (95% CI = -743 to -71). CONCLUSION: FoF is an important psychological factor associated with mobility in glaucoma patients, although specific aspects of mobility (fall rates vs activity levels) affected vary by the degree of FoF. Our findings suggest that customizing behavioral interventions for older adults based on their levels of FoF may be an important strategy for fall prevention and activity promotion. J Am Geriatr Soc 68:1847-1851, 2020.
Efstathiou NE, Moustafa GA, Maidana DE, Konstantinou EK, Notomi S, Barbisan PRT, Georgakopoulos CD, Miller JW, Vavvas DG. Acadesine suppresses TNF-α induced complement component 3 (C3), in retinal pigment epithelial (RPE) cells. PLoS One 2020;15(12):e0244307.Abstract
RATIONALE: Age-related macular degeneration (AMD) is the most prevalent form of irreversible blindness in the developed world. Aging, inflammation and complement dysregulation affecting the retinal pigment epithelium (RPE), are considered significant contributors in its pathogenesis and several evidences have linked tumor necrosis factor alpha (TNF-α) and complement component 3 (C3) with AMD. Acadesine, an analog of AMP and an AMP-activated protein kinase (AMPK) activator, has been shown to have cytoprotective effects in human clinical trials as well as having anti-inflammatory and anti-vascular exudative effects in animals. The purpose of this study was to evaluate if acadesine is able to suppress TNF-α induced C3 in RPE cells. METHODS: ARPE-19 and human primary RPE cells were cultured and allowed to grow to confluence. TNF-α was used for C3 induction in the presence or absence of acadesine. Small molecule inhibitors and siRNA were used to determine if acadesine exerts its effect via the extracellular or intracellular pathway and to evaluate the importance of AMPK for these effects. The expression level of C3 was determined by immunoblot analysis. RESULTS: Acadesine suppresses TNF-α induced C3 in a dose dependent manner. When we utilized the adenosine receptor inhibitor dipyridamole (DPY) along with acadesine, acadesine's effects were abolished, indicating the necessity of acadesine to enter the cell in order to exert it's action. However, pretreatment with 5-iodotubericidin (5-Iodo), an adenosine kinase (AK) inhibitor, didn't prevent acadesine from decreasing TNF-α induced C3 expression suggesting that acadesine does not exert its effect through AMP conversion and subsequent activation of AMPK. Consistent with this, knockdown of AMPK α catalytic subunit did not affect the inhibitory effect of acadesine on TNF-α upregulation of C3. CONCLUSIONS: Our results suggest that acadesine suppresses TNF-α induced C3, likely through an AMPK-independent pathway, and could have potential use in complement over activation diseases.
Elhusseiny AM, Jamerson EC, Menshawey R, Tam EK, El Sayed YM. Collector Channels: Role and Evaluation in Schlemm's Canal Surgery. Curr Eye Res 2020;45(10):1181-1187.Abstract
OBJECTIVES: 1) To elucidate the role of collector channels in the aqueous humor outflow pathway 2) To suggest anatomic and functional methods of imaging collector channels in-vitro and in-vivo and 3) To discuss the role of such imaging modalities in the surgical management of glaucoma. METHODS: A thorough literature search was conducted on databases for studies published in English regarding the available methods to determine the role of collecting channels in normal and glaucomatous patients and to assess their patency. RESULTS: Intraocular pressure (IOP) exists as a balance between aqueous humor production and aqueous humor outflow. Collector channels are an essential anatomical constituent of the distal portion of the conventional aqueous humor outflow pathway. There are different surgical options for glaucoma management and with the recent advances in Schlemm's canal-based surgeries, collector channel's patency became a key factor in determining the optimum management for the glaucomatous eye. The advent of anatomic imaging methods has improved the ability to visualize collector channel morphology in-vitro, including swept-source optical coherence tomography (SS-OCT), spectral domain optical coherence tomography (SD-OCT), micro-computed tomography (micro CT), new immunohistochemistry techniques and scanning electron microscopy. The recent advent of real-time assessment of collector channel patency (including evaluation of episcleral venous outflow, observation of episcleral venous fluid wave, and tracer studies utilizing fluorescein, indocyanine green, and trypan blue) has been validated by the aforementioned anatomic imaging modalities. CONCLUSIONS: New modalities of in-vitro and in-vivo studies of collector channels provide promise to aid in the assessment of collector channel patency and individualization of surgical management for glaucoma patients.
Elhusseiny AM, Wu C, MacKinnon S, Hunter DG. Severe reverse amblyopia with atropine penalization. J AAPOS 2020;
Elhusseiny AM, Gore C, Sadiq MAA, Dagi LR, Kazlas M, Hunter DG. Self-grading effect of inferior oblique myectomy and recession. J AAPOS 2020;Abstract
PURPOSE: To evaluate the outcomes of inferior oblique (IO) weakening surgery, whether recession or myectomy, and to assess the dose-response relationship and correlation with angle of preoperative hypertropia. METHODS: The medical records of all patients with vertical deviation in primary gaze who underwent unilateral IO-weakening surgery, either recession or myectomy, at Boston Children's Hospital over an 8-year period with a minimum postoperative follow-up of 1 month were reviewed retrospectively. Outcome measures were effect of IO weakening surgery on vertical deviation in primary gaze and its correlation with the preoperative angle of hyperdeviation. Secondary outcomes included resolution of abnormal head posture, reduction of ocular torsion, and postoperative under- and overcorrection RESULTS: A total of 94 patients were identified (mean age at surgery, 29.3 ± 19.8 years; range, 1-69). The mean postoperative follow-up period was 17.2 ± 15 months. IO recession was performed in 30 patients; IO myectomy, in 64. Surgical success in primary position was achieved in 72 patients (77%), with resolution of anomalous preoperative head posture in 93%. The mean effect on alignment in primary position was 11.3 ± 6.8. The response to IO-weakening surgery was strongly correlated with the preoperative hyperdeviation for both recession (R = 0.53) and myectomy (R = 0.87). CONCLUSIONS: As with other types of strabismus surgery, IO weakening has a "self-grading" contribution, in which the surgical effect strongly correlates with the magnitude of preoperative deviation. A large range of vertical misalignment can be corrected with the same surgical approach.
Elhusseiny AM, VanderVeen DK. Outcomes of Glaucoma Drainage Devices in Childhood Glaucoma. Semin Ophthalmol 2020;:1-11.Abstract
PURPOSE: Angle surgery is the gold standard for the management of many types of childhood glaucoma, yet glaucoma drainage devices (GDD) are effective tools for refractory advanced cases or secondary childhood glaucomas. The purpose of this article is to review recently published literature focused on the use of GDDs for pediatric glaucoma, including GDD general principles and surgical outcomes. METHODS: Literature review of various electronic databases was performed. RESULTS: 71 papers were reviewed for outcomes of GDD in childhood glaucomas. Success rates were usually defined by intraocular pressure (IOP) of 5-22 mmHg, with or without medications. Success rates were typically higher for non-valved GDDs but varied by length of follow-up. Non-valved GDDs afford lower and longer-lasting IOP control in pediatric eyes than valved GDD, however, no randomized controlled trials exist in childhood glaucoma. CONCLUSION: Various designs of GDDs are available for management of childhood glaucoma with good short-term success rates; individual patient factors should be taken into consideration when selecting a specific device.
Elhusseiny AM, Grush A, Dagi LR. Acute, severe dystonia after strabismus surgery in a patient on propofol, ondansetron, and bupropion. J AAPOS 2020;
Enayati S, Chang K, Achour H, Cho K-S, Xu F, Guo S, Z Enayati K, Xie J, Zhao E, Turunen T, Sehic A, Lu L, Utheim TP, Chen DF. Electrical Stimulation Induces Retinal Müller Cell Proliferation and Their Progenitor Cell Potential. Cells 2020;9(3)Abstract
Non-invasive electrical stimulation (ES) is increasingly applied to improve vision in untreatable eye conditions, such as retinitis pigmentosa and age-related macular degeneration. Our previous study suggested that ES promoted retinal function and the proliferation of progenitor-like glial cells in mice with inherited photoreceptor degeneration; however, the underlying mechanism remains obscure. Müller cells (MCs) are thought to be dormant residential progenitor cells that possess a high potential for retinal neuron repair and functional plasticity. Here, we showed that ES with a ramp waveform of 20 Hz and 300 µA of current was effective at inducing mouse MC proliferation and enhancing their expression of progenitor cell markers, such as (cone-rod homeobox) and , as well as their production of trophic factors, including ciliary neurotrophic factor. RNA sequencing revealed that calcium signaling pathway activation was a key event, with a false discovery rate of 5.33 × 10 ( = 1.78 × 10) in ES-mediated gene profiling changes. Moreover, the calcium channel blocker, nifedipine, abolished the observed effects of ES on MC proliferation and progenitor cell gene induction, supporting a central role of ES-induced Ca signaling in the MC changes. Our results suggest that low-current ES may present a convenient tool for manipulating MC behavior toward neuroregeneration and repair.
Enwemeka CS, Baker TL, Greiner JV, Bumah VV, Masson-Meyers DS, Castel JC, Vesonder M. Antimicrobial Photodynamic Therapy as a Potential Treatment Against COVID-19: A Case for Blue Light. Photobiomodul Photomed Laser Surg 2020;38(10):577-578.
Erickson S, Sullivan AG, Barabino S, Begovic E, Benitez-Del-Castillo JM, Bonini S, Borges JS, Brzheskiy V, Bulat N, Cerim A, Craig P, Cușnir V, Cușnir V, Cușnir V, Doan S, Dülger E, Farrant S, Geerling G, Goldblum D, Golubev S, Gomes JAP, González-Méijome JM, Grupcheva CN, Gündüz UÖmür, Horwath-Winter J, Källmark F, Karanadze N, Karcic HH, Karcic S, Kontadakis G, Messmer EM, Mrugacz M, Murphy C, O'Leary OE, Procopciuc V, Pult H, Raus P, Şahin A, Setälä N, Stanila A, Stanila DM, Utheim TP, Vehof J, Versura P, Villani E, Willcox MDP, Wolffsohn JS, Zagórski Z, Zoega GMár, Sullivan DA, Sullivan DA, Gomes JAP, Versura P, Willcox MDP. TFOS European ambassador meeting: Unmet needs and future scientific and clinical solutions for ocular surface diseases. Ocul Surf 2020;Abstract
The mission of the Tear Film & Ocular Surface Society (TFOS) is to advance the research, literacy, and educational aspects of the scientific field of the tear film and ocular surface. Fundamental to fulfilling this mission is the TFOS Global Ambassador program. TFOS Ambassadors are dynamic and proactive experts, who help promote TFOS initiatives, such as presenting the conclusions and recommendations of the recent TFOS DEWS II™, throughout the world. They also identify unmet needs, and propose future clinical and scientific solutions, for management of ocular surface diseases in their countries. This meeting report addresses such needs and solutions for 25 European countries, as detailed in the TFOS European Ambassador meeting in Rome, Italy, in September 2019.
Escuder AG, Kazlas MA, Heidary G, Hunter DG, Zurakowski D, Dagi LR. Incidence of symptomatic vertical and torsional diplopia after superior rectus transposition for esotropic Duane syndrome and abducens nerve palsy. J AAPOS 2020;Abstract
PURPOSE: To report the incidence of symptomatic vertical and torsional diplopia after superior rectus transposition (SRT) for esotropic Duane syndrome and abducens nerve palsy. METHODS: The medical records of patients with esotropic Duane syndrome or abducens nerve palsy seen at Boston Children's Hospital (2006-2018) and treated with unilateral SRT with or without augmentation was performed. The primary outcome was incidence of postoperative vertical or torsional diplopia in primary position. The secondary outcome was induced vertical deviation in affected side gaze. RESULTS: A total of 69 patients met inclusion criteria: 32 with abducens nerve palsy and 37 with esotropic Duane syndrome. Vertical alignment changed in both hyper- and hypotropic directions. Median pre- and postoperative vertical deviation in primary gaze was 1.1 (10th-90th percentile, 0-6 hypertropia) and 0.4 (10th-90th percentile, 6 hypotropia to 8 hypertropia), respectively. Postoperative vertical diplopia occurred in 7%, including 4 of 49 treated with loop myopexy (8%), 1 of 13 without augmentation (8%), and 0 of 7 treated with sclera-fixated augmentation. All but one was successfully treated with prism or secondary surgery. Intorsional change predominated, but no patient had torsional diplopia post adjustment. Vertical misalignment in affected side gaze increased from 19% to 45% after SRT (P = 0.01). CONCLUSIONS: In this largest-to-date review of patients treated with SRT, with or without MR recession, no patient developed persistent torsional diplopia, while 7% developed symptomatic vertical diplopia in primary position, similar to the reported incidence after balanced vertical rectus transposition. Vertical misalignment in affected side gaze increased, however fusion is already limited by unresolved esotropia in this field.
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Fan N-W, Dohlman TH, Foulsham W, McSoley M, Singh RB, Chen Y, Dana R. The role of Th17 immunity in chronic ocular surface disorders. Ocul Surf 2020;Abstract
Th17 cells have been implicated in the pathogenesis of numerous inflammatory and autoimmune conditions. At the ocular surface, Th17 cells have been identified as key effector cells in chronic ocular surface disease. Evidence from murine studies indicates that following differentiation and expansion, Th17 cells migrate from the lymphoid tissues to the eye, where they release inflammatory cytokines including, but not limited to, their hallmark cytokine IL-17A. As the acute phase subsides, a population of long-lived memory Th17 cells persist, which predispose hosts both to chronic inflammation and severe exacerbations of disease; of great interest is the small subset of Th17/1 cells that secrete both IL-17A and IFN-γ in acute-on-chronic disease exacerbation. Over the past decade, substantial progress has been made in deciphering how Th17 cells interact with the immune and neuroimmune pathways that mediate chronic ocular surface disease. Here, we review (i) the evidence for Th17 immunity in chronic ocular surface disease, (ii) regulatory mechanisms that constrain the Th17 immune response, and (iii) novel therapeutic strategies targeting Th17 cells.
Farinha C, Cachulo ML, Coimbra R, Alves D, Nunes S, Pires I, Marques JP, Costa J, Martins A, Sobral I, Barreto P, Laíns I, Figueira J, Ribeiro L, Cunha-Vaz J, Silva R. Age-Related Macular Degeneration Staging by Color Fundus Photography vs. Multimodal Imaging-Epidemiological Implications (). J Clin Med 2020;9(5)Abstract
Epidemiology of age-related macular degeneration (AMD) is based on staging systems relying on color fundus photography (CFP). We aim to compare AMD staging using CFP to multimodal imaging with optical coherence tomography (OCT), infra-red (IR), and fundus autofluorescence (FAF), in a large cohort from the Epidemiologic AMD Coimbra Eye Study. All imaging exams from the participants of this population-based study were classified by a central reading center. CFP images were graded according to the International Classification and Grading System for AMD and staged with Rotterdam classification. Afterward, CFP images were reviewed with OCT, IR, and FAF and stage update was performed if necessary. Early and late AMD prevalence was compared in a total of 1616 included subjects. In CFP-based grading, the prevalence was 14.11% for early AMD ( = 228) and 1.05% ( = 17) for late AMD, nine cases (0.56%) had neovascular AMD (nAMD) and eight (0.50%) geographic atrophy (GA). Using multimodal grading, the prevalence increased to 14.60% for early AMD ( = 236) and 1.61% ( = 26) for late AMD, with 14 cases (0.87%) of nAMD and 12 (0.74%) of GA. AMD staging was more accurate with the multimodal approach and this was especially relevant for late AMD. We propose that multimodal imaging should be adopted in the future to better estimate and compare epidemiological data in different populations.
Fay A, Nallasamy N, Allen RC, Bernardini FP, Bilyk JR, Cockerham K, Cruz AA, Devoto M, Dolman PJ, Dutton JJ, Jordan DR, Kersten R, Kim Y-D, Lucarelli MJ, McNab AA, Mombaerts I, Mourits M, Nerad J, Perry JD, Rose G, Saeed P, Seah LL, Selva D, Sivak-Callcott J, Strianese D, Verity DH, Verity DH. Perioperative Prophylactic Antibiotics in 1,250 Orbital Surgeries. Ophthalmic Plast Reconstr Surg 2020;36(4):385-389.Abstract
PURPOSE: Intravenous antibiotic prophylaxis is used for many clean-contaminated surgeries or clean surgeries with an implant, but its value for clean orbital surgery has not been determined. This study investigated infection risks and adverse effects related to antibiotics in patients undergoing orbital surgery. METHODS: A prospective, nonrandomized comparative case series of all patients undergoing orbital surgery with participating surgeons between October 1, 2013, and March 1, 2015. Types of surgery, antibiotic regimens, corticosteroid use, antibiotic side effects, and surgical site infections (SSIs) were entered into an electronic database and subsequently analyzed. Cases in which patients received postoperative oral antibiotics were analyzed separately. RESULTS: Of 1,250 consecutive orbital surgeries, 1,225 met inclusion criteria. A total of 1208 patients were included in the primary analysis: 603 received no antibiotic prophylaxis (group A), and 605 received a single dose of intravenous antibiotic (group B). Five patients (0.42%) developed an SSI, 3 in group A and 2 in group B. The difference in SSI rates was not statistically significant between the 2 groups (p = 0.66). Antibiotic prophylaxis, alloplastic implants, paranasal sinus entry, and corticosteroid use were not associated with differences in SSI rates. All SSIs resolved on a single course of oral antibiotics; an implant was removed in 1 case. There were no complications associated with a single dose of intravenous prophylaxis. However, 12% of 17 patients (group C) who received 1 week of oral postoperative prophylactic antibiotics developed antibiotic-related complications (diarrhea, renal injury), yielding a number needed to harm of 8.5. CONCLUSIONS: In this large series, antibiotic prophylaxis does not appear to have reduced the already low incidence of SSI following orbital surgery. Given the detriments of systemic antibiotics, the rarity of infections related to orbital surgery, and the efficacy of treating such infections should they occur, patients undergoing orbital surgery should be educated to the early symptoms of postoperative infection and followed closely, but do not routinely require perioperative antibiotics.
FCRS AMDR, MBBS BB, MD TI, MBBS MS, MS AA, MD GDV, PhD RD, MS AK, DNB MSI, FRCSOphth WM, FRCSEd CSP, MD MP, FRCSGlasg HSL, FRCSEd TS, MD CL, MS BJ, MD NS, MS AM, DNB MP, MD KM, FRCSOphth JN, MD T-TI, DNB BK, MS BS, MD CE, PhD LR, MD A-DH, MD BB, MD IA, MD GDA, MD HCP, PhD B-AT, PhD G-LJJ, MD AS, MS BR, MS MB, MD ES, MD TA, MD NS, DNB AM, MD AS, MD VR, MS SR, MD SA, PhD SK, PhD ZM, MRCP KOM, PhD CET, PhD KJH, PhD NQD, FRCSOphth PC, MS GV. The Collaborative Ocular Tuberculosis Study (COTS)-1: A Multinational Review of 165 Patients with Tubercular Anterior Uveitis. Ocul Immunol Inflamm 2020;:1-10.
Feldstein IT, Dyszak GN. Road crossing decisions in real and virtual environments: A comparative study on simulator validity. Accid Anal Prev 2020;137:105356.Abstract
Virtual reality (VR) is a valuable tool for the assessment of human perception and behavior in a risk-free environment. Investigators should, however, ensure that the used virtual environment is validated in accordance with the experiment's intended research question since behavior in virtual environments has been shown to differ to behavior in real environments. This article presents the street crossing decisions of 30 participants who were facing an approaching vehicle and had to decide at what moment it was no longer safe to cross, applying the step-back method. The participants executed the task in a real environment and also within a highly immersive VR setup involving a head-mounted display (HMD). The results indicate significant differences between the two settings regarding the participants' behaviors. The time-to-contact of approaching vehicles was significantly lower for crossing decisions in the virtual environment than for crossing decisions in the real one. Additionally, it was demonstrated that participants based their crossing decisions in the real environment on the temporal distance of the approaching vehicle (i.e., time-to-contact), whereas the crossing decisions in the virtual environment seemed to depend on the vehicle's spatial distance, neglecting the vehicle's velocity. Furthermore, a deeper analysis suggests that crossing decisions were not affected by factors such as the participant's gender or the order in which they faced the real and the virtual environment.
Feldstein IT, Peli E. Pedestrians Accept Shorter Distances to Light Vehicles Than Dark Ones When Crossing the Street. Perception 2020;49(5):558-566.Abstract
Does the brightness of an approaching vehicle affect a pedestrian's crossing decision? Thirty participants indicated their street-crossing intentions when facing approaching light or dark vehicles. The experiment was conducted in a real daylight environment and, additionally, in a corresponding virtual one. A real road with actual cars provides high face validity, while a virtual environment ensures the scenario's precise reproducibility and repeatability for each participant. In both settings, participants judged dark vehicles to be a more imminent threat-either closer or moving faster-when compared with light ones. Secondary results showed that participants accepted a significantly shorter time-to-contact when crossing the street in the virtual setting than on the real road.
Foulsham W, Mittal SK, Taketani Y, Chen Y, Nakao T, Chauhan SK, Dana R. Aged Mice Exhibit Severe Exacerbations of Dry Eye Disease with an Amplified Memory Th17 Cell Response. Am J Pathol 2020;190(7):1474-1482.Abstract
The prevalence as well as the severity of dry eye disease increase with age. Memory T helper 17 (Th17) cells (CD4IL-17ACD44) drive the chronic and relapsing course of dry eye disease. Here, we investigated the contribution of memory Th17 cells to age-related dry eye disease, and evaluated memory Th17 cell depletion with anti-IL-15 antibody as a strategy to abrogate the severe exacerbations of dry eye disease observed in aged mice. After initial exposure to desiccating stress, aged mice maintained higher frequencies of memory Th17 cells in the draining lymph nodes relative to young mice. Upon secondary exposure to desiccating stress, aged mice developed more severe corneal epitheliopathy than young mice, which is associated with increased local frequencies of Th17 cells (CD4IL-17A). Treatment with anti-IL-15 antibody decreased the enlarged memory Th17 pool in aged mice to frequencies comparable with young mice. Furthermore, anti-IL-15-treated mice showed significantly reduced conjunctival infiltration of Th17 cells and lower corneal fluorescein staining scores compared with saline-treated control mice. Our data suggest that age-related increases in the memory Th17 compartment predispose aged mice toward the development of severe corneal epithelial disease after exposure to a dry environment. Selectively targeting memory Th17 cells may be a viable therapeutic approach in the treatment of age-related dry eye disease.
Francis JH, Berry D, Abramson DH, Barker CA, Bergstrom C, Demirci H, Engelbert M, Grossniklaus H, Hubbard B, Iacob CE, Jaben K, Kurli M, Postow MA, Wolchok JD, Kim IK, Wells JR. Intravitreous Cutaneous Metastatic Melanoma in the Era of Checkpoint Inhibition: Unmasking and Masquerading. Ophthalmology 2020;127(2):240-248.Abstract
PURPOSE: Cutaneous melanoma metastatic to the vitreous is very rare. This study investigated the clinical findings, treatment, and outcome of patients with metastatic cutaneous melanoma to the vitreous. Most patients received checkpoint inhibition for the treatment of systemic disease, and the significance of this was explored. DESIGN: Multicenter, retrospective cohort study. PARTICIPANTS: Fourteen eyes of 11 patients with metastatic cutaneous melanoma to the vitreous. METHODS: Clinical records, including fundus photography and ultrasound results, were reviewed retrospectively, and relevant data were recorded for each patient eye. MAIN OUTCOME MEASURES: Clinical features at presentation, ophthalmic and systemic treatments, and outcomes. RESULTS: The median age at presentation of ophthalmic disease was 66 years (range, 23-88 years), and the median follow-up from diagnosis of ophthalmic disease was 23 months. Ten of 11 patients were treated with immune checkpoint inhibition at some point in the treatment course. The median time from starting immunotherapy to ocular symptoms was 17 months (range, 4.5-38 months). Half of eyes demonstrated amelanotic vitreous debris. Five eyes demonstrated elevated intraocular pressure, and 4 eyes demonstrated a retinal detachment. Six patients showed metastatic disease in the central nervous system. Ophthalmic treatment included external beam radiation (30-40 Gy) in 6 eyes, intravitreous melphalan (10-20 μg) in 4 eyes, enucleation of 1 eye, and local observation while receiving systemic treatment in 2 eyes. Three eyes received intravitreous bevacizumab for neovascularization. The final Snellen visual acuity ranged from 20/20 to no light perception. CONCLUSIONS: The differential diagnosis of vitreous debris in the context of metastatic cutaneous melanoma includes intravitreal metastasis, and this seems to be particularly apparent during this era of treatment with checkpoint inhibition. External beam radiation, intravitreous melphalan, and systemic checkpoint inhibition can be used in the treatment of ophthalmic disease. Neovascular glaucoma and retinal detachments may occur, and most eyes show poor visual potential. Approximately one quarter of patients demonstrated ocular disease that preceded central nervous system metastasis. Patients with visual symptoms or vitreous debris in the context of metastatic cutaneous melanoma would benefit from evaluation by an ophthalmic oncologist.
Francis JH, Jaben K, Santomasso BD, Canestraro J, Abramson DH, Chapman PB, Berkenstock M, Aronow ME. Immune Checkpoint Inhibitor-Associated Optic Neuritis. Ophthalmology 2020;127(11):1585-1589.

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