All

Kumase F, Takeuchi K, Morizane Y, Suzuki J, Matsumoto H, Kataoka K, Al-Moujahed A, Maidana DE, Miller JW, Vavvas DG. AMPK-Activated Protein Kinase Suppresses Ccr2 Expression by Inhibiting the NF-κB Pathway in RAW264.7 Macrophages. PLoS One 2016;11(1):e0147279.Abstract

C-C chemokine receptor 2 (Ccr2) is a key pro-inflammatory marker of classic (M1) macrophage activation. Although Ccr2 is known to be expressed both constitutively and inductively, the full regulatory mechanism of its expression remains unclear. AMP-activated protein kinase (AMPK) is not only a master regulator of energy homeostasis but also a central regulator of inflammation. In this study, we sought to assess AMPK's role in regulating RAW264.7 macrophage Ccr2 protein levels in resting (M0) or LPS-induced M1 states. In both M0 and M1 RAW264.7 macrophages, knockdown of the AMPKα1 subunit by siRNA led to increased Ccr2 levels whereas pharmacologic (A769662) activation of AMPK, attenuated LPS-induced increases in Ccr2 expression in an AMPK dependent fashion. The increases in Ccr2 levels by AMPK downregulation were partially reversed by NF-κB inhibition whereas TNF-a inhibition had minimal effects. Our results indicate that AMPK is a negative regulator of Ccr2 expression in RAW264.7 macrophages, and that the mechanism of action of AMPK inhibition of Ccr2 is mediated, in part, through the NF-κB pathway.

Grob SR, Yoon MK. Central Retinal Vein Occlusion Resolving After Orbital Decompression in Thyroid Eye Disease. Ophthal Plast Reconstr Surg 2016;Abstract

A 49-year-old male presented with proptosis and was found to have optic nerve edema with peripapillary hemorrhages. Diagnostic testing showed a suppressed thyroid-stimulating hormone. CT orbits showed homogenous tendon-sparing enlargement of the medial and inferior rectus muscles, characteristic of thyroid eye disease. Intravenous methylprednisolone was administered given the concern for compressive optic neuropathy. He initially had improvement of his symptoms, so orbital decompression was deferred. Subsequently he presented with worsening diplopia and right proptosis, a new afferent pupillary defect, and a cecocentral visual field defect. Dilated examination revealed significant optic nerve head edema and diffuse retinal hemorrhages in all 4 quadrants consistent with a central retinal vein occlusion. The patient underwent an urgent 3-wall orbital decompression on the right. Close follow up postoperatively showed resolution of the central retinal vein occlusion and the associated optic disc edema, peripapillary hemorrhages, and macular edema. Orbital decompression is known to improve many manifestations of thyroid eye disease, but this is the first report of orbital decompression resulting in resolution of a central retinal vein occlusion.

Silva PS, Cavallerano JD, Haddad NMN, Tolls D, Thakore K, Patel B, Sehizadeh M, Tolson AM, Sun JK, Aiello LP. Comparison of Nondiabetic Retinal Findings Identified With Nonmydriatic Fundus Photography vs Ultrawide Field Imaging in an Ocular Telehealth Program. JAMA Ophthalmol 2016;134(3):330-4.Abstract

IMPORTANCE: Ultrawide field imaging (UWFI) is increasingly being used in teleophthalmology settings. Given the greater area of the retina imaged, we evaluated the ability of UWFI vs nonmydriatic fundus photography (NMFP) to detect nondiabetic retinal findings in a teleophthalmology program. OBSERVATION: We conducted a retrospective single-center comparative cohort study from January 1, 2011, to June 30, 2013, imaging 3864 and 3971 consecutive teleophthalmology patients (7728 and 7942 eyes) using NMFP and UWFI, respectively. Standard diabetic retinopathy evaluation and nondiabetic findings were compared between the 2 imaging modalities. In patients without diabetic retinopathy (2243 by NMFP and 2252 by UWFI), the rate of identification of nondiabetic findings by NMFP (451 patients [20.1%]) and UWFI (490 [21.8%]) were comparable (P = .19). Ultrawide field imaging increased the identification of choroidal nevi by 27% (406 eyes [5.3%] by NMFP vs 545 eyes [6.9%] by UWFI; P < .001) and chorioretinal atrophy or scarring by 116% (50 eyes [0.6%] by NMFP vs 101 eyes [1.3%] by UWFI; P < .001). No peripheral retinal findings were identified with NMFP, while UWFI detected 25 retinal tears (0.3%; P < .001), 54 lattice and peripheral degenerations (0.7%; P < .001), and 142 cases of vitreous detachment or floaters (1.8%; P < .001). Data analysis was performed from November 1, 2013, to May 1, 2014. CONCLUSIONS AND RELEVANCE: In eyes without diabetic retinopathy, approximately 20% may have ocular findings identified on retinal imaging, which emphasizes the role of retinal imaging in patients with diabetes mellitus type 1 and type 2 regardless of the severity of retinopathy. In this cohort, UWFI increased the identification of peripheral retinal and vitreous pathologic findings.

Le H-G, Saeed H, Mantagos IS, Mitchell CM, Goverman J, Chodosh J. Burn unit care of Stevens Johnson syndrome/toxic epidermal necrolysis: A survey. Burns 2016;42(4):830-5.Abstract

Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) is a systemic disease that can be associated with debilitating acute and chronic complications across multiple organ systems. As patients with acute SJS/TEN are often treated in a burn intensive care unit (BICU), we surveyed burn centers across the United States to determine their approach to the care of these patients. The goal of our study was to identify best practices and possible variations in the care of patients with acute SJS/TEN. We demonstrate that the method of diagnosis, use of systemic therapies, and involvement of subspecialists varied significantly between burn centers. Beyond supportive care provided to every patient, our data highlights a lack of standardization in the acute care of patients with SJS/TEN. A comprehensive guideline for the care of patients with acute SJS/TEN is indicated.

Vazirani J, Ali MH, Sharma N, Gupta N, Mittal V, Atallah M, Amescua G, Chowdhury T, Abdala-Figuerola A, Ramirez-Miranda A, Navas A, Graue-Hernández EO, Chodosh J. Autologous simple limbal epithelial transplantation for unilateral limbal stem cell deficiency: multicentre results. Br J Ophthalmol 2016;100(10):1416-20.Abstract

PURPOSE: To report outcomes of autologous simple limbal epithelial transplantation (SLET) performed for unilateral limbal stem cell deficiency (LSCD) at multiple centres worldwide. METHODS: In this retrospective, multicentre, interventional case series, records of patients who had undergone autologous SLET for unilateral LSCD, with a minimum of 6 months of follow-up, were reviewed. The primary outcome measure was clinical success, defined as a completely epithelised, avascular corneal surface. Kaplan-Meier survival curves were constructed and survival probability was calculated. A Cox proportional hazards analysis was done to assess association of preoperative characteristics with risk of failure. Secondary outcome measures included the percentage of eyes achieving visual acuity of 20/200 or better, percentage of eyes gaining two or more Snellen lines and complications encountered. RESULTS: 68 eyes of 68 patients underwent autologous SLET, performed across eight centres in three countries. Clinical success was achieved in 57 cases (83.8%). With a median follow-up of 12 months, survival probability exceeded 80%. Presence of symblepharon (HR 5.8) and simultaneous keratoplasty (HR 10.8) were found to be significantly associated with a risk of failure. 44 eyes (64.7%) achieved a visual acuity of 20/200 or better, and 44 eyes (64.7%) gained two or more Snellen lines. Focal recurrences of pannus were noted in 21 eyes (36.8%) with clinical success. CONCLUSION: Autologous SLET is an effective and safe modality for treatment of unilateral LSCD. Clinical success rates and visual acuity improvement are equal to or better than those reported with earlier techniques.

Kim YJ, Payal AR, Daly MK. Effects of tear gases on the eye. Surv Ophthalmol 2016;61(4):434-42.Abstract

Chemical agents that target the eyes have been a popular choice for law enforcement during riots and for military training for nearly a century. The most commonly used agents are chloroacetophenone (formerly sold as Mace), o-chlorobenzylidene malononitrile, and oleoresin capsicum (OC or pepper spray, current ingredient for Mace). Initially, most severe ocular injuries were caused by the explosive force rather than the chemical itself. The development of sprays reduced the mechanical severity of ocular injuries, but resulted in a variety of chemical injuries. The effects on eyes include conjunctival injection, complete corneal epithelial defects, pseudopterygium, corneal neovascularization, persistent conjunctivalization, corneal opacities, and reduced visual acuity. Current management, based on limited human studies, emphasizes decontamination and symptomatic treatment. We review the literature related to clinical and histopathologic effects of tear gas agents on the eye and their management.

Wolfe JM, Aizenman AM, Boettcher SEP, Cain MS. Hybrid foraging search: Searching for multiple instances of multiple types of target. Vision Res 2016;119:50-9.Abstract

This paper introduces the "hybrid foraging" paradigm. In typical visual search tasks, observers search for one instance of one target among distractors. In hybrid search, observers search through visual displays for one instance of any of several types of target held in memory. In foraging search, observers collect multiple instances of a single target type from visual displays. Combining these paradigms, in hybrid foraging tasks observers search visual displays for multiple instances of any of several types of target (as might be the case in searching the kitchen for dinner ingredients or an X-ray for different pathologies). In the present experiment, observers held 8-64 target objects in memory. They viewed displays of 60-105 randomly moving photographs of objects and used the computer mouse to collect multiple targets before choosing to move to the next display. Rather than selecting at random among available targets, observers tended to collect items in runs of one target type. Reaction time (RT) data indicate searching again for the same item is more efficient than searching for any other targets, held in memory. Observers were trying to maximize collection rate. As a result, and consistent with optimal foraging theory, they tended to leave 25-33% of targets uncollected when moving to the next screen/patch. The pattern of RTs shows that while observers were collecting a target item, they had already begun searching memory and the visual display for additional targets, making the hybrid foraging task a useful way to investigate the interaction of visual and memory search.

Wen G, Aizenman A, Drew T, Wolfe JM, Haygood TM, Markey MK. Computational assessment of visual search strategies in volumetric medical images. J Med Imaging (Bellingham) 2016;3(1):015501.Abstract

When searching through volumetric images [e.g., computed tomography (CT)], radiologists appear to use two different search strategies: "drilling" (restrict eye movements to a small region of the image while quickly scrolling through slices), or "scanning" (search over large areas at a given depth before moving on to the next slice). To computationally identify the type of image information that is used in these two strategies, 23 naïve observers were instructed with either "drilling" or "scanning" when searching for target T's in 20 volumes of faux lung CTs. We computed saliency maps using both classical two-dimensional (2-D) saliency, and a three-dimensional (3-D) dynamic saliency that captures the characteristics of scrolling through slices. Comparing observers' gaze distributions with the saliency maps showed that search strategy alters the type of saliency that attracts fixations. Drillers' fixations aligned better with dynamic saliency and scanners with 2-D saliency. The computed saliency was greater for detected targets than for missed targets. Similar results were observed in data from 19 radiologists who searched five stacks of clinical chest CTs for lung nodules. Dynamic saliency may be superior to the 2-D saliency for detecting targets embedded in volumetric images, and thus "drilling" may be more efficient than "scanning."

Vodopivec I, Prasad S. Treatment of Susac Syndrome. Curr Treat Options Neurol 2016;18(1):3.Abstract

OPINION STATEMENT: Susac syndrome is a microangiopathy of the brain, retina, and cochlea. Several lines of evidence support the concept that this disease is an acquired autoimmune disorder. Prospective, randomized, controlled studies of treatments are not available because the disease is rare. Furthermore, the average period of follow-up in reported cases is short, limiting a complete understanding of the natural history of the disease. Empirical treatment strategies are therefore based upon expert recommendations and anecdotal reports of response to various immunomodulators, and the appropriate duration of therapy is not known. In our opinion, the encephalopathic form of Susac syndrome should be treated early and aggressively to avoid cognitive dysfunction and disability. Induction therapy with pulse methylprednisolone frequently proves to be inadequate. Additional agents, including intravenous immunoglobulins, intravenous cyclophosphamide, or rituximab are often necessary to induce a sustained remission. Maintenance therapy with oral glucocorticoids combined with intravenous immunoglobulins, mycophenolate mofetil, methotrexate, azathioprine, cyclophosphamide, or rituximab is typically necessary to achieve a sustained remission. Aspirin may be used as an adjunctive agent, although evidence showing efficacy is scant. The response to treatment should be closely monitored by frequent clinical examinations, brain MRI, and fluorescein angiography. Once disease remission has been established, it appears prudent to continue maintenance treatment for at least two additional years, although the real long-term risk of future relapses remains unknown. Establishing a multicenter patient registry and biorepository is essential to study the pathogenesis of the disease, further define the duration of disease, identify reliable biomarkers that aid early diagnosis and assess risk of relapse, and develop effective disease-specific therapies.

Afrogheh AH, Jakobiec FA, Hammon R, Grossniklaus HE, Rocco J, Lindeman NI, Sadow PM, Faquin WC. Evaluation for High-risk HPV in Squamous Cell Carcinomas and Precursor Lesions Arising in the Conjunctiva and Lacrimal Sac. Am J Surg Pathol 2016;40(4):519-28.Abstract

High-risk human papilloma virus (HR-HPV) is a well-established causative agent of oropharyngeal squamous cell carcinoma (SCC). In addition, HR-HPV has occasionally been reported to be present in dysplastic and malignant lesions of the conjunctiva and lacrimal sac, although its overall incidence and etiological role in periocular SCC are controversial. Sequential surgical samples of 52 combined cases of invasive SCC (I-SCC) and SCC in situ (SCCIS) from 2 periocular sites (conjunctiva and lacrimal sac) diagnosed over a 14-year period (2000 to 2014) were selected for evaluation, and relevant patient characteristics were documented. p16 immunohistochemistry was performed as a screening test. All p16-positive cases were further evaluated for HR-HPV using DNA in situ hybridization (DNA ISH), and a subset was also analyzed by polymerase chain reaction (PCR). Of 43 ocular surface squamous neoplasias (OSSNs), 30% (n=13; 8 SCCIS and 5 I-SCC cases) were positive for HR-HPV. HPV-positive OSSNs occurred in 8 men and 5 women with a mean age of 60 years (range, 39 to 94 y). HPV type-16 was detected in all conjunctival cases evaluated by PCR. All 5 conjunctival I-SCCs were nonkeratinizing (n=4) or partially keratinizing (n=1) and managed by simple excision. In contrast, HPV-negative conjunctival I-SCCs were predominantly keratinizing (11 keratinizing and 2 nonkeratinizing). Of 9 lacrimal sac I-SCCs (LSSCCs), 66.7% (n=6) were positive for HR-HPV by p16 and DNA ISH; HPV subtypes were HPV-16 (n=5) and HPV-58 (n=1). In addition, 2 p16-positive cases with negative DNA ISH results were HR-HPV positive (HPV-16 and HPV-33) when evaluated by PCR, suggesting that the rate of HR-HPV positivity among the LSSCCs may be as high as 89% (n=8). The combined group of HR-HPV-positive LSSCCs was seen in 4 men and 4 women with a mean age of 60 years (range, 34 to 71 y). Seven of the 8 HPV-positive LSSCCs (87.5%) had a nonkeratinizing or partially keratinizing histomorphology, whereas 1 case (12.5%) was predominantly keratinizing. The presence of HR-HPV in 30% of OSSNs and at least 66.7% of LSSCCs suggests the possibility of an etiologic role for HR-HPV at these sites.

Chao W, Belmonte C, Benitez Del Castillo J, Bron A, Dua H, Nichols K, Novack G, Schrader S, Willcox M, Wolffsohn J, Sullivan DA. Report of the Inaugural Meeting of the TFOS i2 = initiating innovation Series: Targeting the Unmet Need for Dry Eye Treatment (London, United Kingdom, March 21, 2015). Ocul Surf 2016;Abstract

In March 2015, a meeting was held in London, United Kingdom, to address the progress in targeting the unmet need for dry eye disease (DED) treatment. The meeting, which launched the i(2) = initiating innovation series, was sponsored by the Tear Film & Ocular Surface Society (TFOS; www.TearFilm.org) and supported by Dompé. The TFOS i(2) meeting was designed to review advances in the understanding of DED since publication of the 2007 TFOS International Dry Eye WorkShop (DEWS) report, and to help launch the highly anticipated sequel, DEWS II. The meeting was structured to discuss the scope of the DED problem, to review the clinical challenges of DED, and to consider the treatment challenges of DED. This article provides a synopsis of the presentations of this TFOS i(2) meeting.

Ginat DT, Glass LRD, Yanoga F, Lee NG, Freitag SK. Lacrimal gland abscess presenting with preseptal cellulitis depicted on CT. J Ophthalmic Inflamm Infect 2016;6(1):1.Abstract

BACKGROUND: Pyogenic lacrimal gland abscesses are uncommon and thus may not be immediately clinically recognized without a high index of suspicion. FINDINGS: We present two patients with preseptal cellulitis and characteristic low-attenuation fluid collections in the lacrimal glands demonstrated on computed tomography (CT). CONCLUSIONS: Lacrimal gland abscesses should be considered when dacryoadenitis is refractory to medical treatment. Indeed, these cases highlight the value of prompt recognition of lacrimal abscess through ophthalmologic referral and the use of diagnostic imaging. Both patients were successfully treated via incision and drainage.

Jiang D, Xiao X, Fu T, Mashaghi A, Liu Q, Hong J. Transient Tear Film Dysfunction after Cataract Surgery in Diabetic Patients. PLoS One 2016;11(1):e0146752.Abstract

PURPOSE: Diabetes mellitus is an increasingly common systemic disease. Many diabetic patients seek cataract surgery for a better visual acuity. Unlike in the general population, the influence of cataract surgery on tear film function in diabetic patients remains elusive. The aim of this study was to evaluate the tear function in diabetic and nondiabetic patients following cataract surgery. METHODS: In this prospective, interventional case series, 174 diabetic patients without dry eye syndrome (DES) and 474 age-matched nondiabetic patients as control who underwent phacoemulsification were enrolled at two different eye centers between January 2011 and January 2013. Patients were followed up at baseline and at 7 days, 1 month, and 3 months postoperatively. Ocular symptom scores (Ocular Surface Disease Index, OSDI) and tear film function including tear film stability (tear film break-up time, TBUT), corneal epithelium integrity (corneal fluorescein staining, CFS), and tear secretion (Schirmer's I test, SIT) were evaluated. RESULTS: In total, 83.9% of the diabetic patients (146 cases with 185 eyes) and 89.0% of the nondiabetic patients (422 cases with 463 eyes) completed all check-ups after the interventions (P = 0.095). The incidence of DES was 17.1% in the diabetic patients and 8.1% in the nondiabetic patients at 7 days after cataract surgery. In the diabetic patients, the incidence of DES remained 4.8% at 1 month postoperatively and decreased to zero at 3 months after surgery. No DES was diagnosed in nondiabetic patients at either the 1-month or 3-month follow-up. Compared with the baseline, the diabetic patients had worse symptom scores and lower TBUT values at 7 days and 1 month but not at 3 months postoperatively. In the nondiabetic patients, symptom scores and TBUT values had returned to preoperative levels at 1-month check-up. CFS scores and SIT values did not change significantly postoperatively in either group (P = 0.916 and P = 0.964, respectively). CONCLUSIONS: Diabetic patients undergoing cataract surgery are prone to DES. Ocular symptoms and tear film stability are transiently worsened in diabetic patients and are restored more slowly than those in nondiabetic patients.

Pages