Sophie X. Deng

Ocular TRUST: Nationwide Antimicrobial Susceptibility Patterns in Ocular Isolates

PURPOSE Ocular Tracking Resistance in U.S. Today (TRUST) annually evaluates in vitro antimicrobial susceptibility of Staphylococcus aureus, Streptococcus pneumoniae, and Haemophilus influenzae to ciprofloxacin, gatifloxacin, levofloxacin, moxifloxacin, penicillin, azithromycin, tobramycin, trimethoprim, and polymyxin B in national samples of ocular isolates. DESIGN Laboratory investigation. METHODS Prospectively collected ocular isolates (197 S. aureus, 49 S. pneumoniae, and 32 H. influenzae) from 35 institutions and archived ocular isolates (760 S. pneumoniae and 356 H. influenzae) from 34 institutions were tested by an independent, central laboratory. Mean minimum inhibitory concentrations that would inhibit growth of 90% of the tested isolates (MIC(90)) were interpreted as susceptible, intermediate, or resistant according to standardized breakpoints for systemic treatment. S. aureus isolates were classified as methicillin susceptible (MSSA) or methicillin resistant (MRSA). RESULTS MSSA or MRSA susceptibility patterns were virtually identical for the fluoroquinolones, that is, MSSA susceptibility was 79.9% to 81.1% and MRSA susceptibility was 15.2%. Trimethoprim was the only agent tested with high activity against MRSA. All S. pneumoniae isolates were susceptible to gatifloxacin, levofloxacin, and moxifloxacin; 89.8% were susceptible to ciprofloxacin. H. influenzae isolates were 100% susceptible to all tested agents but trimethoprim. Ocular TRUST 1 data were consistent with the eight-year longitudinal sample of archived ocular isolates. CONCLUSIONS The fluoroquinolones were consistently active in MSSA, S. pneumoniae, and H. influenzae. After more than a decade of intensive ciprofloxacin and levofloxacin use as systemic therapy, 100% of ocular S. pneumoniae isolates were susceptible to gatifloxacin, levofloxacin, and moxifloxacin; nonsusceptibility to ciprofloxacin was less than 15%. High-level in vitro MRSA resistance suggests the need to consider alternative therapy to fluoroquinolones when MRSA is a likely pathogen.

Options and Adjuvants in Surgery for Pterygium: A Report by the American Academy of Ophthalmology

OBJECTIVE To assess the outcomes and safety of current surgical options and adjuvants in the treatment of primary and recurrent pterygium. METHODS Literature searches of the PubMed and the Cochrane Library databases were last conducted in January 2011 using keywords and were restricted to randomized controlled trials reporting on surgical intervention for pterygium. The searches were limited to articles published in English and yielded 120 citations. Citation abstracts, and if necessary the full text, were reviewed to identify randomized controlled trials that reported recurrence as an outcome measure and had a mean follow-up of at least 6 months. Fifty-one studies comparing bare sclera excision, conjunctival or limbal autograft, intraoperative mitomycin C, postoperative mitomycin C, and amniotic membrane transplantation for primary and recurrent pterygia fit these inclusion criteria. RESULTS Four studies demonstrated that the conjunctival or limbal autograft procedure is more efficacious than amniotic membrane placement. Use of conjunctival or limbal autografts or mitomycin C during or after pterygium excision reduced recurrence compared with bare sclera excision alone in most studies of primary or recurrent pterygium. The outcomes of conjunctival or limbal autograft were similar to outcomes for intraoperative mitomycin C in the few studies that directly compared the 2 techniques. There is evidence that increased concentration and duration of exposure to intraoperative mitomycin C is associated with increased efficacy. Of the adjuvants studied, only mitomycin C was associated with vision-threatening complications, including scleral thinning, ulceration, and delayed conjunctival epithelialization; there is some evidence of increasing complications with increased concentration and duration of exposure. There is conflicting evidence as to whether increasing age is protective against recurrence, but the morphologic features of the pterygium were shown to affect the recurrence rate. CONCLUSIONS Evidence indicates that bare sclera excision of pterygium results in a significantly higher recurrence rate than excision accompanied by use of certain adjuvants. Conjunctival or limbal autograft was superior to amniotic membrane graft surgery in reducing the rate of pterygium recurrence. Among other adjuvants, there is evidence that mitomycin C and conjunctival or limbal autografts reduce the recurrence rate after surgical excision of a pterygium. Furthermore, the data indicate that using a combination of conjunctival or limbal autograft with mitomycin C further reduces the recurrence rate after pterygium excision compared with conjunctival or limbal autograft or mitomycin C alone. Additional studies are necessary to determine the long-term effects, optimal route of administration, and dose and duration of treatment for mitomycin C. Factors such as availability of resources, primary or recurrent status of pterygium, age of patient, and surgeon or patient preference may influence the surgeons choice of adjuvant because there are insufficient data to recommend a specific adjuvant as superior. FINANCIAL DISCLOSURE(S) Proprietary or commercial disclosure may be found after the references.

A new tonometer--the Corvis ST tonometer: clinical comparison with noncontact and Goldmann applanation tonometers.

PURPOSE To compare intraocular pressure (IOP) measurements obtained using the Topocon noncontact tonometer (NCT), the Goldmann applanation tonometer (GAT), and the Corvis ST (CST), a newly developed tonometer with features of visualization and measurement of the corneal deformation response to an air impulse. A secondary objective was to assess the agreement among the devices. METHODS Fifty-nine participants, including glaucoma patients (36 cases) and control volunteers (23 cases), were enrolled. One eye was selected randomly for further study. IOP measurements were obtained with the CST, NCT, and GAT by two experienced clinicians. IOP values were compared. Intraobserver variability and interobserver variability were assessed by the coefficient of variation and intraclass correlation coefficient. Device agreement was calculated by Bland-Altman analysis. RESULTS Mean IOP for all examined eyes was 18.9 ± 5.8 mm Hg for CST, 21.3 ± 6.8 mm Hg for NCT, and 20.3 ± 5.7 mm Hg for GAT. There was no statistically significant difference in IOP measurements among the tonometers except between the CST and NCT. Correlation analysis showed a high correlation between each pair of devices (all P < 0.001). The CST displayed the best intraobserver variability and interobserver variability. Bland-Altman analysis revealed a bias between CST and GAT, CST and NCT, and GAT and NCT of -1.3, -2.4, and -1.1 mm Hg, with 95% limits of agreement of -6.2 to 3.5 mm Hg, -10.1 to 5.2 mm Hg, and -8.3 to 6.2 mm Hg, respectively. CONCLUSIONS The CST offers an alternative method for measuring IOP. IOP measurements taken with these devices may not be interchangeable.

Wnt/β-Catenin Signaling Regulates Proliferation of Human Cornea Epithelial Stem/Progenitor Cells

PURPOSE To investigate the expression and role of the Wnt signaling pathway in human limbal stem cells (LSCs). METHODS Total RNA was isolated from the human limbus and central cornea. Limbal or cornea-specific transcripts were identified through quantitative real-time PCR. Protein expression of Wnt molecules was confirmed by immunohistochemistry on human ocular tissue. Activation of Wnt signaling using lithium chloride was achieved in vitro and its effects on LSC differentiation and proliferation were evaluated. RESULTS Expression of Wnt2, Wnt6, Wnt11, Wnt16b, and four Wnt inhibitors were specific to the limbal region, whereas Wnt3, Wnt7a, Wnt7b, and Wnt10a were upregulated in the central cornea. Nuclear localization of β-catenin was observed in a very small subset of basal epithelial cells only at the limbus. Activation of Wnt/β-catenin signaling increased the proliferation and colony-forming efficiency of primary human LSCs. The stem cell phenotype was maintained, as shown by higher expression levels of putative corneal epithelial stem cell markers, ATP-binding cassette family G2 and ΔNp63α, and low expression levels of mature cornea epithelial cell marker, cytokeratin 12. CONCLUSIONS These findings demonstrate for the first time that Wnt signaling is present in the ocular surface epithelium and plays an important role in the regulation of LSC proliferation. Modulation of Wnt signaling could be of clinical application to increase the efficiency of ex vivo expansion of corneal epithelial stem/progenitor cells for transplantation.

TFOS DEWS II Management and Therapy Report

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.

Characterization of Limbal Stem Cell Deficiency by In Vivo Laser Scanning Confocal Microscopy: A Microstructural Approach

OBJECTIVE To evaluate the cellular changes in the corneal epithelium and surrounding structures in limbal stem cell deficiency (LSCD) by using in vivo laser scanning confocal microscopy. METHODS This was a prospective comparative study that included 27 eyes of 20 patients with LSCD and 12 eyes of 10 healthy subjects. All subjects underwent slitlamp examination, and LSCD was classified into 3 groups on the basis of clinical presentation. Confocal imaging of the central cornea and 4 locations of limbus was performed. Morphologic characteristics of the corneal epithelium were studied. The basal epithelial cell density and subbasal nerve density in the central cornea were calculated, and a potential correlation between the decrease in basal epithelial cell density and subbasal nerve density in LSCD was investigated. RESULTS The wing and basal epithelial cells became progressively metaplastic, and the basal epithelial cell density and subbasal nerve density in the early and intermittent stages decreased significantly compared with controls (all P < .01). Normal basal epithelial cell morphology was completely lost and subbasal nerves were absent in the late stage of LSCD. The decrease in basal cell density correlated with the decrease in subbasal nerve density in patients with LSCD (P = .03). CONCLUSIONS There are significant microstructural changes associated with early LSCD. These cellular changes could help to understand the disease process and classify and monitor limbal stem cell dysfunction.

Presentation, diagnosis and management of limbal stem cell deficiency.

The human corneal surface epithelium is continuously repopulated by the limbal stem cells (LSCs). Limbal Stem Cell Deficiency (LSCD) can lead to corneal opacity and vascularization, with consequent visual impairment or blindness. Many acquired and congenital diseases can lead to LCSD by direct injury to the LSCs, destruction of LSC niche, or both. Based on the severity of the disease, LSCD can present with various symptoms and signs. Although LSCD can be detected clinically, laboratory tests are necessary to confirm the diagnosis and monitor the disease progression. This article concisely reviews the clinical presentation, techniques for diagnosis and management of LSCD.

Outcomes after DSEK in 101 eyes with previous trabeculectomy and tube shunt implantation.

Purpose: The aim of this study was to determine the outcomes after Descemet stripping endothelial keratoplasty (DSEK) in eyes with previous glaucoma surgery. Methods: This is a retrospective review of all DSEK procedures performed by 2 surgeons from May 1, 2006, to December 31, 2012. Results: Four hundred sixty-two DSEK procedures were performed, of which 113 (24%) were performed in 101 eyes after a trabeculectomy (52 procedures) and/or tube shunt implantation (76 procedures) (15 procedures in eyes with both). Primary graft failure and donor dislocation developed in 4.4% and 14.2% of cases in eyes with previous glaucoma surgery, not significantly different from the 3.2% (P = 0.56) and 11.5% (P = 0.51) in eyes without prior glaucoma surgery. During a mean follow-up of 20.7 ± 17.6 months, endothelial rejection developed in a greater percentage of eyes with previous glaucoma surgery (12.9%; 0.069/eye-year) compared with that in eyes without surgery (6.9%; 0.042/eye-year), although the difference was not statistically significant (P = 0.066 for percentage of eyes; P = 0.16 for rejection rate). Secondary graft failure developed in a significantly higher percentage of eyes with previous glaucoma surgery (15.9%; 0.094/eye-year) compared with that in eyes without surgery (3.2%; 0.019/eye-year) (P < 0.0001; P < 0.0001). Elevated intraocular pressure after DSEK was significantly more common in eyes with medically treated glaucoma (41.3%; 0.345/eye year) than in eyes with a previous glaucoma surgery (23.8%; 0.145/eye-year) and without glaucoma (20.0%; 0.138/eye year) (P = 0.009; P = 0.007). Conclusions: Although intraoperative and early postoperative complications such as donor dislocation and primary graft failure are not significantly more common after DSEK in eyes with previous glaucoma surgery, secondary graft failure is. In contrast, other postoperative complications such as elevated intraocular pressure are significantly more common in eyes with medically treated glaucoma than in eyes with previous glaucoma surgery and without glaucoma.

Boston Keratoprosthesis: Outcomes and Complications: A Report by the American Academy of Ophthalmology

OBJECTIVE To review the published literature on safety and outcomes of the Boston type I keratoprosthesis (BI-KPro) for the surgical treatment of corneal opacification not amenable to human cadaveric corneal transplantation. METHODS Searches of peer-reviewed literature were conducted in PubMed and the Cochrane Library in December 2012, July 2013, and January 2014 without date restrictions. The searches were limited to studies published in English and yielded 587 citations. The abstracts of these articles were reviewed, 48 articles were selected for possible clinical relevance, and 22 were determined to be relevant for the assessment objectives. Nine studies were rated as level II evidence and 13 studies were rated as level III evidence. Excluded were level III evidence, case reports, review articles, letters, editorials, and case series with fewer than 25 eyes. RESULTS In 9 articles, a best-corrected Snellen visual acuity (BCSVA) of 20/200 or better occurred in 45% to 89% of eyes. Five articles described a BCSVA of 20/50 or better in 43% to 69% of eyes, and 4 articles found a BCSVA of 20/40 or better in 11% to 39% of eyes. Retention rates of the BI-KPro ranged from 65% to 100%. Reasons for loss of vision after BI-KPro implantation most commonly included corneal melts resulting from exposure keratopathy, endophthalmitis, and infectious keratitis or corneal ulceration. The 2 most common complications after surgery were retroprosthetic membrane formation (range, 1.0%-65.0%; mean ± standard deviation [SD], 30.0±19.0%) and elevated intraocular pressure (range, 2.4%-64.0%; mean ± SD, 27.5±18.1%). The 2 most common posterior segment complications were endophthalmitis (range, 0%-12.5%; mean ± SD, 4.6±4.6%) and vitritis (range, 0%-14.5%; mean ± SD, 5.6±4.7%). CONCLUSIONS The reviewed articles on BI-KPro use suggest that the device improves vision in cases of severe corneal opacification that were not amenable to corneal transplantation using human cadaveric keratoplasty techniques. A number of severe anterior and posterior segment complications can develop as follow-up continues, making ongoing close observation paramount for patients undergoing this surgery. These complications include infection, device extrusion, and permanent vision loss.

Identification of novel molecular markers through transcriptomic analysis in human fetal and adult corneal endothelial cells

The corneal endothelium is composed of a monolayer of corneal endothelial cells (CECs), which is essential for maintaining corneal transparency. To better characterize CECs in different developmental stages, we profiled mRNA transcriptomes in human fetal and adult corneal endothelium with the goal to identify novel molecular markers in these cells. By comparing CECs with 12 other tissue types, we identified 245 and 284 signature genes that are highly expressed in fetal and adult CECs, respectively. Functionally, these genes are enriched in pathways characteristic of CECs, including inorganic anion transmembrane transporter, extracellular matrix structural constituent and cyclin-dependent protein kinase inhibitor activity. Importantly, several of these genes are disease target genes in hereditary corneal dystrophies, consistent with their functional significance in CEC physiology. We also identified stage-specific markers associated with CEC development, such as specific members in the transforming growth factor beta and Wnt signaling pathways only expressed in fetal, but not in adult CECs. Lastly, by the immunohistochemistry of ocular tissues, we demonstrated the unique protein localization for Wnt5a, S100A4, S100A6 and IER3, the four novel markers for fetal and adult CECs. The identification of a new panel of stage-specific markers for CECs would be very useful for characterizing CECs derived from stem cells or ex vivo expansion for cell replacement therapy.