Jakobiec FA, Qureshi S, Zakka FR, Tu Y, Lee NG. Eyelid Eccrine Cyst: An Exceptional Lesion Among Dominant Apocrine Cysts. Ophthal Plast Reconstr Surg 2017;33(5):e128-e131.Abstract
A 71-year-old woman developed a small bluish lesion beneath the cilia of the left lower eyelid. Excision and microscopic examination disclosed a cyst with an intimately associated eccrine sweat gland. Immunohistochemistry demonstrated that the cyst's epithelium was strongly CK5/6, CK14, CK7 weakly positive, and gross cystic disease fluid protein-15 and smooth muscle actin negative. This is the first immunohistochemically proven eccrine cyst of the eyelid skin. Apocrine cysts develop only at the eyelid margin where the glands of Moll are located. They immunostain positively for cytoplasmic gross cystic disease fluid protein-15 in the adlumenal cells and smooth muscle actin in an outer myoepithelial (abluminal) layer.
Jakobiec FA, Stagner AM, Eagle RC, Lally SE, Krane JF. Unusual pleomorphic adenoma of the lacrimal Gland: Immunohistochemical demonstration of PLAG1 and HMGA2 oncoproteins. Surv Ophthalmol 2017;62(2):219-226.Abstract

Painless low-grade right proptosis with 20/25 visual acuity developed slowly in a 49-year-old woman with a past history of breast cancer. Imaging studies disclosed an oval-to-round superotemporal mass in the right lacrimal fossa without bone erosion. Excisional biopsy revealed a pseudoencapsulated, bosselated tumor with a spindled, hypocellular, and heavily periodic acid Schiff-positive stroma constituted of abundant basement membrane material and collagen. Scattered lumens and focal cribriform cellular clusters were present in the peripheries of several of the lobules. Immunohistochemistry showed epithelial membrane antigen+ and cytokeratin (CK) 7+ in many small luminal structures. The spindled cells were calponin+, CK5/6+, CK14+, and p63+, confirming their myoepithelial nature. The Ki67 proliferation index was 2-3%, and upregulation of nuclear p53, a tumor suppressor gene product which may be aberrantly overexpressed in malignancy, was observed in rare cells. Immunohistochemical probes for HMGA2 and PLAG1 oncoproteins, characteristic of pleomorphic adenoma, were stained intensely and less intensely, respectively. MYB and c-KIT (CD117) were negative, thereby strongly arguing against the diagnosis of adenoid cystic carcinoma. In atypical epithelial tumors of the lacrimal gland, genetic probes identifying distinctive gene translocations or their oncoprotein products complement traditional immunohistochemical biomarkers such as cytokeratins and other structural or secretory molecules. Characteristic genetic abnormalities demonstrated by immunohistochemistry for their upregulated protein products, or by in situ hybridization for translocations, are increasingly being relied on for diagnostic precision.

Jakobs TC. Ex Vivo Imaging of the Murine Optic Nerve Head. Invest Ophthalmol Vis Sci 2017;58(2):734.
Jamuar SS, Schmitz-Abe K, D'Gama AM, Drottar M, Chan W-M, Peeva M, Servattalab S, Lam A-TN, Delgado MR, Clegg NJ, Zayed ZA, Dogar MA, Alorainy IA, Jamea AA, Abu-Amero K, Griebel M, Ward W, Lein ES, Markianos K, Barkovich JA, Robson CD, Grant EP, Bosley TM, Engle EC, Walsh CA, Yu TW. Biallelic mutations in human DCC cause developmental split-brain syndrome. Nat Genet 2017;49(4):606-612.Abstract

Motor, sensory, and integrative activities of the brain are coordinated by a series of midline-bridging neuronal commissures whose development is tightly regulated. Here we report a new human syndrome in which these commissures are widely disrupted, thus causing clinical manifestations of horizontal gaze palsy, scoliosis, and intellectual disability. Affected individuals were found to possess biallelic loss-of-function mutations in the gene encoding the axon-guidance receptor 'deleted in colorectal carcinoma' (DCC), which has been implicated in congenital mirror movements when it is mutated in the heterozygous state but whose biallelic loss-of-function human phenotype has not been reported. Structural MRI and diffusion tractography demonstrated broad disorganization of white-matter tracts throughout the human central nervous system (CNS), including loss of all commissural tracts at multiple levels of the neuraxis. Combined with data from animal models, these findings show that DCC is a master regulator of midline crossing and development of white-matter projections throughout the human CNS.

Jee D, Keum N, Kang S, Arroyo JG. Sleep and diabetic retinopathy. Acta Ophthalmol 2017;95(1):41-47.Abstract

PURPOSE: To investigate the association between sleep duration and diabetic retinopathy (DR). METHODS: A population-based cross-sectional study using a nation-wide, systemically stratified, multistage, clustered sampling method included a total of 1670 subjects aged ≥40 years with diabetes who participated in the Korean National Health and Nutrition Examination Survey during 2008-2012. All participants performed standardized interviews, including self-reported sleep duration, and comprehensive ophthalmic examinations. Seven standard retinal fundus photographs were obtained from both eyes after pupil dilatation. Diabetic retinopathy (DR) was graded and classified as any DR and vision-threatening DR. Participants were stratified into men and women. RESULTS: The mean sleep duration was 6.71 hr/day. In men, adjusted OR of any DR was 1.88 [95% confidence interval (OR), 1.01-3.59] in those with ≤5 hr sleep, and 2.19 (95% CI, 1.01-4.89) in those with ≥9 hr sleep, compared to in subjects with 6-8 hr sleep, after adjusting for potential confounders including age, body mass index (BMI), diabetes duration, fasting glucose level, haemoglobin A1c levels and hypertension. In women, however, no significant association between sleep duration and DR was found. The vision-threatening DR was not significantly associated with sleep duration in either men or women. CONCLUSIONS: Short and long sleep was associated with high prevalence of DR in men. Sleep deprivation may be involved in the pathogenesis of DR development.

Jeng-Miller KW, Cestari DM, Gaier ED. Congenital anomalies of the optic disc: insights from optical coherence tomography imaging. Curr Opin Ophthalmol 2017;28(6):579-586.Abstract
PURPOSE OF REVIEW: Congenital anomalies of the optic nerve are rare but significant causes of visual dysfunction in children and adults. Accurate diagnosis is dependent on a thorough funduscopic examination, but can be enhanced by imaging information garnered from optical coherence tomography (OCT). We review common congenital optic nerve anomalies, including optic disc pit, optic nerve coloboma, morning glory disc anomaly, and hypoplasia of the optic nerve, review their systemic associations, and discuss insights from OCT imaging. RECENT FINDINGS: Optic disc pits are a result of a defect in the lamina cribrosa and abnormal vitreomacular adhesions have been shown to cause maculopathy. In patients with optic nerve colobomas, OCT can be instrumental in diagnosing choroidal neovascularization, a rare but visually devastating complication. The pathogenesis of morning glory disc anomaly has been more clearly elucidated by OCT as occurring from a secondary postnatal mesenchymal abnormality rather than only the initial neuroectodermal dysgenesis of the terminal optic stalk in isolation. OCT studies of optic nerve hypoplasia have demonstrated significant thinning of the inner and outer retinal layers of the perifoveal region and thicker layers in the fovea itself, resulting in a foveal hypoplasia-like pathology, that is, significantly correlated to poorer visual outcomes. SUMMARY: OCT provides detailed in-vivo analysis of these anatomic anomalies and their resulting pathologies, shedding new insights on the pathogenesis, diagnosis, and potential visual outcomes of these conditions in children. Further study employing OCT to elucidate structure-function relationships of congenital optic nerve anomalies will help expand the role of OCT in clinical practice related to diagnosis, prognosis, and management of these entities.
Ji YW, Mittal SK, Hwang HS, Chang E-J, Lee JH, Seo Y, Yeo A, Noh H, Lee HS, Chauhan SK, Lee HK. Lacrimal gland-derived IL-22 regulates IL-17-mediated ocular mucosal inflammation. Mucosal Immunol 2017;10(5):1202-1210.Abstract
Inflammatory damage of mucosal surface of the eye is a hallmark of dry eye disease (DED) and, in severe cases, can lead to significant discomfort, visual impairment, and blindness. DED is a multifactorial autoimmune disorder with a largely unknown pathogenesis. Using a cross-sectional patient study and a well-characterized murine model of DED, herein we investigated the immunoregulatory function of interleukin-22 (IL-22) in the pathogenesis of DED. We found that IL-22 levels were elevated in lacrimal fluids of DED patients and inversely correlated with severity of disease. Acinar cells of the lacrimal glands (LGs), not inflammatory immune cells, are the primary source of IL-22, which suppresses inflammation in ocular surface epithelial cells upon desiccating stress. Moreover, loss of function analyses using IL-22 knockout mice demonstrated that IL-22 is essential for suppression of ocular surface infiltration of Th17 cells and inhibition of DED induction. Our novel findings elucidate immunoregulatory function of LG-derived IL-22 in inhibiting IL-17-mediated ocular surface epitheliopathy in DED thus making IL-22 a new relevant therapeutic target.
Jiménez-Pérez JC, Jakobiec FA, Zakka FR, Yoon MK. Dacryoadenitis as the Initial Presentation of a Natural Killer T-Cell Lymphoma. Ophthal Plast Reconstr Surg 2017;33(6):e147-e150.Abstract
Primary orbital natural killer T-cell lymphoma (NKTCL) is a rare condition with only a few published cases in the literature. Over 1 month, an 81-year-old man developed progressive left periocular inflammation unresponsive to treatment. Clinical examination and imaging studies demonstrated a left lacrimal gland enlargement. Bilateral anterior uveitis and erythematous nontender cutaneous lesions were also found. Biopsies of the skin and lacrimal gland on the back revealed histopathologic and immunohistochemical findings confirming Epstein-Barr virus-positive NKTCL. Metastatic work up disclosed multifocal involvement in the pancreas, stomach, and chest wall. Palliative treatment consisting of nonanthracycline-based chemotherapy and radiation was instituted, but the patient died 5 months after the onset of symptoms. This is the first example of acute dacryoadenitis, and the second of bilateral anterior uveitis, in the setting of NKTCL. Absence of naso-sinus involvement in the current case is rare in NKTCL. Despite treatment, the prognosis remains dismal. Orbital specialists should include NKTCL in the differential diagnosis of lacrimal gland/orbital masses and perform an incisional biopsy if the clinical scenario so dictates.
Johnson CP, Kim IK, Esmaeli B, Amin-Mansour A, Treacy DJ, Carter SL, Hodis E, Wagle N, Seepo S, Yu X, Lane AM, Gragoudas ES, Vazquez F, Nickerson E, Cibulskis K, McKenna A, Gabriel SB, Getz G, Van Allen EM, 't Hoen PAC, Garraway LA, Woodman SE. Systematic genomic and translational efficiency studies of uveal melanoma. PLoS One 2017;12(6):e0178189.Abstract
To further our understanding of the somatic genetic basis of uveal melanoma, we sequenced the protein-coding regions of 52 primary tumors and 3 liver metastases together with paired normal DNA. Known recurrent mutations were identified in GNAQ, GNA11, BAP1, EIF1AX, and SF3B1. The role of mutated EIF1AX was tested using loss of function approaches including viability and translational efficiency assays. Knockdown of both wild type and mutant EIF1AX was lethal to uveal melanoma cells. We probed the function of N-terminal tail EIF1AX mutations by performing RNA sequencing of polysome-associated transcripts in cells expressing endogenous wild type or mutant EIF1AX. Ribosome occupancy of the global translational apparatus was sensitive to suppression of wild type but not mutant EIF1AX. Together, these studies suggest that cells expressing mutant EIF1AX may exhibit aberrant translational regulation, which may provide clonal selective advantage in the subset of uveal melanoma that harbors this mutation.
Jones L, Downie LE, Korb D, Benitez-Del-Castillo JM, Dana R, Deng SX, Dong PN, Geerling G, Hida RY, Liu Y, Seo KY, Tauber J, Wakamatsu TH, Xu J, Wolffsohn JS, Craig JP. TFOS DEWS II Management and Therapy Report. Ocul Surf 2017;15(3):575-628.Abstract
The members of the Management and Therapy Subcommittee undertook an evidence-based review of current dry eye therapies and management options. Management options reviewed in detail included treatments for tear insufficiency and lid abnormalities, as well as anti-inflammatory medications, surgical approaches, dietary modifications, environmental considerations and complementary therapies. Following this extensive review it became clear that many of the treatments available for the management of dry eye disease lack the necessary Level 1 evidence to support their recommendation, often due to a lack of appropriate masking, randomization or controls and in some cases due to issues with selection bias or inadequate sample size. Reflecting on all available evidence, a staged management algorithm was derived that presents a step-wise approach to implementing the various management and therapeutic options according to disease severity. While this exercise indicated that differentiating between aqueous-deficient and evaporative dry eye disease was critical in selecting the most appropriate management strategy, it also highlighted challenges, based on the limited evidence currently available, in predicting relative benefits of specific management options, in managing the two dry eye disease subtypes. Further evidence is required to support the introduction, and continued use, of many of the treatment options currently available to manage dry eye disease, as well as to inform appropriate treatment starting points and understand treatment specificity in relation to dry eye disease subtype.
Joseph A, Pasquale LR. Attributes Associated with Adherence to Glaucoma Medical Therapy and its Effects on Glaucoma Outcomes: An Evidence-Based Review and Potential Strategies to Improve Adherence. Semin Ophthalmol 2017;32(1):86-90.Abstract

The treatment paradigm in glaucoma classically starts with exhausting all medical therapy prior to proceeding with laser or incisional surgery, although laser-first and surgery-first strategies have been explored in randomized clinical trials. Although glaucoma drops are proven to work well to lower intraocular pressure, slow the conversion from ocular hypertension, and slow the progression of disease in early open angle glaucoma, adherence to treatment is likely optimum in the randomized clinical trials that support these claims. In real-world scenarios, medical therapy often fails and practitioners are forced to proceed with more invasive treatment modalities to slow the progression of this blinding disease. This review aims to take an evidence-based approach to study the risk factors for poor adherence in glaucoma patients, to determine whether poor adherence is, in fact, associated with worse outcomes, and to seek potential strategies to improve adherence in these patients.

Joyal J-S, Gantner ML, Smith LEH. Retinal energy demands control vascular supply of the retina in development and disease: The role of neuronal lipid and glucose metabolism. Prog Retin Eye Res 2018;64:131-156.
Junk AK, Chen PP, Lin SC, Nouri-Mahdavi K, Radhakrishnan S, Singh K, Chen TC. Disinfection of Tonometers: A Report by the American Academy of Ophthalmology. Ophthalmology 2017;124(12):1867-1875.Abstract
OBJECTIVE: To examine the efficacy of various disinfection methods for reusable tonometer prisms in eye care and to highlight how disinfectants can damage tonometer tips and cause subsequent patient harm. METHODS: Literature searches were conducted last in October 2016 in the PubMed and the Cochrane Library databases for original research investigations. Reviews, non-English language articles, nonophthalmology articles, surveys, and case reports were excluded. RESULTS: The searches initially yielded 64 unique citations. After exclusion criteria were applied, 10 laboratory studies remained for this review. Nine of the 10 studies used tonometer prisms and 1 used steel discs. The infectious agents covered in this assessment include adenovirus 8 and 19, herpes simplex virus (HSV) 1 and 2, human immunodeficiency virus 1, hepatitis C virus, enterovirus 70, and variant Creutzfeldt-Jakob disease. All 4 studies of adenovirus 8 concluded that after sodium hypochlorite (dilute bleach) disinfection, the virus was undetectable, but only 2 of the 4 studies found that 70% isopropyl alcohol (e.g., alcohol wipes or soaks) eradicated all viable virus. All 3 HSV studies concluded that both sodium hypochlorite and 70% isopropyl alcohol eliminated HSV. Ethanol, 70% isopropyl alcohol, dilute bleach, and mechanical cleaning all lack the ability to remove cellular debris completely, which is necessary to prevent prion transmission. Therefore, single-use tonometer tips or disposable tonometer covers should be considered when treating patients with suspected prion disease. Damage to tonometer prisms can be caused by sodium hypochlorite, 70% isopropyl alcohol, 3% hydrogen peroxide, ethyl alcohol, water immersion, ultraviolet light, and heat exposure. Disinfectants can cause tonometer tips to swell and crack by dissolving the glue that holds the hollow tip together. The tonometer tip cracks can irritate the cornea, harbor microbes, or allow disinfectants to enter the interior of the tonometer tip. CONCLUSIONS: Sodium hypochlorite (dilute bleach) offers effective disinfection against adenovirus and HSV, the viruses commonly associated with nosocomial outbreaks in eye care. Tonometer prisms should be examined regularly for signs of damage.
Kaufman AR, Nosé RM, Lu Y, Pineda R. Phacoemulsification with intraocular lens implantation after previous descemetorhexis without endothelial keratoplasty. J Cataract Refract Surg 2017;43(11):1471-1475.Abstract
A 58-year-old woman with bilateral Fuchs endothelial corneal dystrophy presented with predominantly central guttata in the left eye causing visually significant stromal edema. A 4.0 mm descemetorhexis without endothelial keratoplasty was performed. At the 6-week follow-up, the central cornea had cleared completely and the central endothelial cell density (ECD) was 541 cells/mm2. The central corneal clearing remained stable for 2 years after the procedure; however, vision declined because of a visually significant cataract in the left eye. Uneventful phacoemulsification with intraocular lens implantation was performed with a target refraction of -0.50 diopters. At 1.5 months postoperatively, the uncorrected distance visual acuity was 20/20 with a manifest refraction of -0.25 -0.25 × 60 and the central ECD was 2373 cells/mm2 (increased from 1471 cells/mm2 prior to phacoemulsification). Cataract surgery by phacoemulsification years after descemetorhexis without endothelial keratoplasty appears to be well-tolerated, with good clinical and predictive refractive outcomes.
Kemp PS, Shah AS, Elliott AT, Wan MJ. Removal of a barbed fish hook from the cornea of an 8-year-old boy. J AAPOS 2017;
Khajavi M, Zhou Y, Birsner AE, Bazinet L, Rosa Di Sant A, Schiffer AJ, Rogers MS, Krishnaji ST, Hu B, Nguyen V, Zon L, D'Amato RJ. Identification of Padi2 as a novel angiogenesis-regulating gene by genome association studies in mice. PLoS Genet 2017;13(6):e1006848.Abstract
Recent findings indicate that growth factor-driven angiogenesis is markedly influenced by genetic variation. This variation in angiogenic responsiveness may alter the susceptibility to a number of angiogenesis-dependent diseases. Here, we utilized the genetic diversity available in common inbred mouse strains to identify the loci and candidate genes responsible for differences in angiogenic response. The corneal micropocket neovascularization assay was performed on 42 different inbred mouse strains using basic fibroblast growth factor (bFGF) pellets. We performed a genome-wide association study utilizing efficient mixed-model association (EMMA) mapping using the induced vessel area from all strains. Our analysis yielded five loci with genome-wide significance on chromosomes 4, 8, 11, 15 and 16. We further refined the mapping on chromosome 4 within a haplotype block containing multiple candidate genes. These genes were evaluated by expression analysis in corneas of various inbred strains and in vitro functional assays in human microvascular endothelial cells (HMVECs). Of these, we found the expression of peptidyl arginine deiminase type II (Padi2), known to be involved in metabolic pathways, to have a strong correlation with a haplotype shared by multiple high angiogenic strains. In addition, inhibition of Padi2 demonstrated a dosage-dependent effect in HMVECs. To investigate its role in vivo, we knocked down Padi2 in transgenic kdrl:zsGreen zebrafish embryos using morpholinos. These embryos had disrupted vessel formation compared to control siblings. The impaired vascular pattern was partially rescued by human PADI2 mRNA, providing evidence for the specificity of the morphant phenotype. Taken together, our study is the first to indicate the potential role of Padi2 as an angiogenesis-regulating gene. The characterization of Padi2 and other genes in associated pathways may provide new understanding of angiogenesis regulation and novel targets for diagnosis and treatment of a wide variety of angiogenesis-dependent diseases.
Kheirkhah A, Crnej A, Ren A, Mullins A, Satitpitakul V, Hamrah P, Schaumberg D, Dana R. Patients' Perceived Treatment Effectiveness in Dry Eye Disease. Cornea 2017;36(8):893-897.Abstract
PURPOSE: Patients' perceptions of the effectiveness of a treatment, or perceived treatment effectiveness (PTE), play an important role in medicine. This study aimed to evaluate patients' PTE in dry eye disease (DED) and investigate factors contributing to these patients' perceptions. METHODS: This cross-sectional study included 66 patients with DED. At enrollment, all patients had comprehensive ophthalmic assessment. In addition, to evaluate the patient's PTE, they were asked to use a 10-point scale ranging from "strongly disagree (score 1)" to "strongly agree (score 10)" to score their views on whether their DED treatments had been effective. Changes in clinical parameters of DED over time during their care were also evaluated retrospectively and correlated with the patients' PTE. RESULTS: The mean age of patients was 55.7 years; 79% were women. Regarding patients' PTE, 36.4% strongly (score 10) and 53.0% moderately (scores 6-9) believed that their DED treatment had been effective. However, 10.6% thought that their treatment had not been effective (scores 1-5). Less favorable PTE for the DED treatment was significantly associated with a younger age (P < 0.001), current use of antidepressant medications (P = 0.01), and a higher Ocular Surface Disease Index score (P = 0.01) at enrollment. CONCLUSIONS: A majority of patients with DED have positive perceptions regarding the effectiveness of their treatments. Less favorable perceptions are associated with more severe ocular symptoms and nonocular parameters such as younger age and current antidepressant use. In DED management, assessing patients' PTE should be considered as an important part of clinical practice.
Kheirkhah A, Di Zazzo A, Satitpitakul V, Fernandez M, Magilavy D, Dana R. A Pilot Randomized Trial on Safety and Efficacy of a Novel Topical Combined Inhibitor of Janus Kinase 1/3 and Spleen Tyrosine Kinase for GVHD-Associated Ocular Surface Disease. Cornea 2017;36(7):799-804.Abstract
PURPOSE: Janus kinase (JAK) and spleen tyrosine kinase (SYK) play critical functions in T-cell activation and in inflammation. Because of their antiinflammatory effects, JAK and SYK inhibitors have recently been evaluated in several immunopathogenic disorders. This pilot study was designed to assess the safety and efficacy of a topical combined JAK/SYK inhibitor, R348, ophthalmic solution for treatment of ocular surface disease in graft-versus-host disease (GVHD). METHODS: This phase 2, double-masked, randomized, pilot trial included 30 patients with ocular surface disease due to GVHD who were randomized to receive topical 0.5% R348, 0.2% R348, or vehicle, twice daily for 12 weeks. Before and after treatment, a comprehensive ophthalmic evaluation was performed, which included Ocular Surface Disease Index (OSDI) questionnaire, Ocular Comfort Index questionnaire, corneal fluorescein staining, conjunctival lissamine green staining, and Schirmer test with anesthesia. Changes in these parameters were compared between the 3 groups. RESULTS: The mean decrease in total corneal fluorescein staining at 12 weeks after treatment was higher in the 0.5% R348 group (-6.0 ± 3.9, NEI scoring) compared with the vehicle (-2.1 ± 2.6, P = 0.045) or the 0.2% R348 group (-4.1 ± 3.6, P = 0.34). However, there were no significant differences among the groups in terms of treatment-induced changes in OSDI, Ocular Comfort Index, conjunctival lissamine green staining, or Schirmer scores. R348 eye drops were well tolerated. CONCLUSIONS: This pilot study indicates that 0.5% R348 JAK/SYK inhibitor ophthalmic solution is well tolerated and may have some therapeutic efficacy in treating ocular GVHD. Larger trials are required to derive more definitive data.
Kheirkhah A, Syed ZA, Satitpitakul V, Goyal S, Müller R, Tu EY, Dana R. Sensitivity and Specificity of Laser-Scanning In Vivo Confocal Microscopy for Filamentous Fungal Keratitis: Role of Observer Experience. Am J Ophthalmol 2017;179:81-89.Abstract
PURPOSE: To determine sensitivity and specificity of laser-scanning in vivo confocal microscopy (LS-IVCM) for detection of filamentous fungi in patients with microbial keratitis and to evaluate the effect of observer's imaging experience on these parameters. DESIGN: Retrospective reliability study. METHODS: This study included 21 patients with filamentous fungal keratitis and 24 patients with bacterial keratitis (as controls). The etiology of infection was confirmed based on the response to specific therapy regardless of culture results. All patients had undergone full-thickness corneal imaging by a LS-IVCM (Heidelberg Retina Tomograph 3 with Rostock Cornea Module; Heidelberg Engineering, Heidelberg, Germany). The images were evaluated for the presence of fungal filaments by 2 experienced observers and 2 inexperienced observers. All observers were masked to the clinical and microbiologic data. RESULTS: The mean number of images obtained per eye was 917 ± 353. The average sensitivity of LS-IVCM for detecting fungal filaments was 71.4% ± 0% for the experienced observers and 42.9% ± 6.7% for the inexperienced observers. The average specificity was 89.6% ± 3.0% and 87.5% ± 17.7% for these 2 groups of observers, respectively. Although there was a good agreement between the 2 experienced observers (κ = 0.77), the inexperienced observers showed only a moderate interobserver agreement (κ = 0.51). The LS-IVCM sensitivity was higher in patients with fungal infections who had positive culture or longer duration of the disease. CONCLUSIONS: Although LS-IVCM has a high specificity for diagnosing filamentous fungal keratitis, its sensitivity is moderate and highly dependent on the level of the observer's experience and training with this imaging modality.
Kheirkhah A, Satitpitakul V, Hamrah P, Dana R. Patients With Dry Eye Disease and Low Subbasal Nerve Density Are at High Risk for Accelerated Corneal Endothelial Cell Loss. Cornea 2016;Abstract

PURPOSE: To evaluate changes in corneal endothelial cell density over time in patients with dry eye disease (DED) and to correlate endothelial cell loss with corneal subbasal nerve density. METHODS: This retrospective study included 40 eyes of 20 patients with DED. Laser in vivo confocal microscopy had been performed in the central cornea of both eyes at an initial visit and repeated after a mean follow-up of 33.2 ± 10.2 months. The densities of corneal endothelial cells and subbasal nerves were measured in both visits and compared with 13 eyes of 13 normal age-matched controls. RESULTS: At the initial visit, the DED group had lower densities of corneal endothelial cells (2620 ± 386 cells/mm) and subbasal nerves (17.8 ± 7.5 mm/mm) compared with the control group (2861 ± 292 cells/mm and 22.8 ± 3.0 mm/mm, with P = 0.08 and P = 0.01, respectively). At the end of follow-up, although there was no significant change in subbasal nerve density (16.7 ± 7.2 mm/mm, P = 0.43), the mean corneal endothelial cell density significantly decreased to 2465 ± 391 cells/mm (P = 0.01), with a mean corneal endothelial cell loss of 2.1 ± 3.6% per year. The endothelial cell loss showed a statistically significant negative correlation with the initial subbasal nerve density (Rs = -0.55, P = 0.02). CONCLUSIONS: Patients with DED have an accelerated corneal endothelial cell loss compared with that reported in the literature for normal aging. Those with lower subbasal nerve density, in particular, are at a higher risk for endothelial cell loss over time.