PURPOSE: Explore differences in green compared with yellow focal/grid laser treatment on functional and anatomical endpoints in eyes with diabetic macular edema. METHODS: Data from two randomized clinical trials were evaluated for differences in visual acuity and optical coherence tomography parameters for eyes assigned to sham injection + prompt laser, ranibizumab + prompt laser, or prompt laser only: among subgroups of eyes treated exclusively and electively with either green or yellow laser. RESULTS: In the sham injection + prompt laser group, the mean visual acuity letter score change for eyes receiving green and yellow laser treatment, respectively, was +2.4 ± 14 and +5.1 ± 13 at the 52-week visit (P = 0.06) and +2.4 ± 15 and +6.0 ± 13 at the 104-week visit (P = 0.13), with no corresponding evidence of differences in optical coherence tomography thickness. When comparing wavelength groups in the ranibizumab + prompt laser and prompt laser-only groups, meaningful differences in visual acuity and optical coherence tomography thickness were not detected at 1 year or 2 years. CONCLUSION: A trend toward improved vision outcome with yellow laser observed in one trial was not corroborated by anatomical outcomes or by the other trial. In this study, without random assignment to different wavelengths controlling for bias and confounding, it is not possible to determine whether one wavelength is better than the other.
The Boston keratoprosthesis (B-KPro), currently the most commonly used artificial cornea worldwide, can provide rapid visual rehabilitation for eyes with severe corneal opacities not suitable for standard corneal transplantation. However, the B-KPro presently needs a corneal graft as a tissue carrier. Although corneal allograft tissue is readily available in the United States and other developed countries with established eye banks, the worldwide need vastly exceeds supply. Therefore, a simple, safe, and inexpensive alternative to corneal allografts is desirable for the developing world. We are currently exploring reasonable alternative options such as corneal autografts, xenografts, noncorneal autologous tissues, and laboratory-made tissue constructs, as well as modifications to corneal allografts, such as deep-freezing, glycerol-dehydration, gamma irradiation, and cross-linking. These alternative tissue carriers for the B-KPro are discussed with special regard to safety, practicality, and cost for the developing world.
PURPOSE: To compare the operating room performance of ophthalmology residents trained by traditional wet-lab versus surgical simulation on the continuous curvilinear capsulorhexis (CCC) portion of cataract surgery. SETTING: Academic tertiary referral center. DESIGN: Prospective randomized study. METHODS: Residents who chose to participate and provided informed consent were randomized to preoperative CCC training in the wet lab or on a simulator. Residents completed pre-practice demographic questionnaires including habits of daily living. After completion of their preoperative training (wet lab versus simulator), residents performed their first CCC of the clinical rotation under the direct supervision of an attending physician as part of their standard training at the facility. Residents then completed satisfaction questionnaires regarding their preoperative training. Two attending surgeons reviewed and graded each video of operating room performance. The mean score between the 2 attending physicians was used as the individual performance score for each of the 12 performance criteria. The overall score was calculated as the sum of these 12 individual performance scores (standardized). RESULTS: Ten residents trained in the wet lab and 11 on the simulator. There was no significant difference in overall score between the 2 groups (P=.608). There was no significant difference in any individual score except time (wet-lab group faster than simulator group) (P=.038). CONCLUSIONS: Preoperative simulator training prepared residents for the operating room as effectively as the wet lab. The time to pass the simulator curriculum was predictive of the time and overall performance in the operating room. FINANCIAL DISCLOSURE: No author has a financial or proprietary interest in any material or method mentioned.
PURPOSE: Letter acuity, the predominant clinical assessment of vision, is relatively insensitive to slow vision loss caused by eye disease. While the contrast sensitivity function (CSF) has demonstrated the potential to monitor the slow progress of blinding eye diseases, current tests of CSF lack the reliability or ease-of-use to capture changes in vision timely. To improve the current state of home testing for vision, we have developed and validated a computerized adaptive test on a commercial tablet device (iPad) that provides an efficient and easy-to-use assessment of the CSF. METHODS: We evaluated the reliability, accuracy, and flexibility of tablet-based CSF assessment. Repeated tablet-based assessments of the spatial CSF, obtained from four normally-sighted observers, which each took 3 to 5 minutes, were compared to measures obtained on CRT-based laboratory equipment; additional tablet-based measures were obtained from six subjects under three different luminance conditions. RESULTS: A Bland-Altman analysis demonstrated that tablet-based assessment was reliable for estimating sensitivities at specific spatial frequencies (coefficient of repeatability 0.14-0.40 log units). The CRT- and tablet-based results demonstrated excellent agreement with absolute mean sensitivity differences <0.05 log units. The tablet-based test also reliably identified changes in contrast sensitivity due to different luminance conditions. CONCLUSIONS: We demonstrate that CSF assessment on a mobile device is indistinguishable from that obtained with specialized laboratory equipment. We also demonstrate better reliability than tests used currently for clinical trials of ophthalmic therapies, drugs, and devices.
Common variable immune deficiency (CVID) is characterized by reduced serum immune globulins and impaired or absent antibody responses. Patients become more susceptible to infections and to lymphoproliferation and granulomatous inflammation. Ophthalmic manifestations of CVID are rare. The authors describe a case of orbital follicular hyperplasia in a 15-year-old girl with CVID syndrome causing proptosis and exposure keratopathy.
Resolution of inflammation is an active process mediated by pro-resolution lipid mediators. As resolvin (Rv) D1 is produced in the cornea, pro-resolution mediators could be effective in regulating inflammatory responses to histamine in allergic conjunctivitis. Two key mediators of resolution are the D-series resolvins RvD1 or aspirin-triggered RvD1 (AT-RvD1). We used cultured conjunctival goblet cells to determine whether histamine actions can be terminated during allergic responses. We found cross-talk between two types of G protein-coupled receptors (GPRs), as RvD1 interacts with its receptor GPR32 to block histamine-stimulated H1 receptor increases in intracellular [Ca(2+)] ([Ca(2+)]i) preventing H1 receptor-mediated responses. In human and rat conjunctival goblet cells, RvD1 and AT-RvD1 each block histamine-stimulated secretion by preventing its increase in [Ca(2+)]i and activation of extracellular regulated-protein kinase (ERK)1/2. We suggest that D-series resolvins regulate histamine responses in the eye and offer new treatment approaches for allergic conjunctivitis or other histamine-dependent pathologies.
Photoreceptor cell death is the ultimate cause of vision loss in various retinal disorders, including retinal detachment (RD). Photoreceptor cell death has been thought to occur mainly through apoptosis, which is the most characterized form of programmed cell death. The caspase family of cysteine proteases plays a central role for inducing apoptosis, and in experimental models of RD, dying photoreceptor cells exhibit caspase activation; however, there is a paradox that caspase inhibition alone does not provide a sufficient protection against photoreceptor cell loss, suggesting that other mechanisms of cell death are involved. Recent accumulating evidence demonstrates that non-apoptotic forms of cell death, such as autophagy and necrosis, are also regulated by specific molecular machinery, such as those mediated by autophagy-related proteins and receptor-interacting protein kinases, respectively. Here we summarize the current knowledge of cell death signaling and its roles in photoreceptor cell death after RD and other retinal degenerative diseases. A body of studies indicate that not only apoptotic but also autophagic and necrotic signaling are involved in photoreceptor cell death, and that combined targeting of these pathways may be an effective neuroprotective strategy for retinal diseases associated with photoreceptor cell loss.
PURPOSE: The rate at which the orbit matures is not well-documented. Limiting this pursuit are the difficulties inherent in measuring orbital volumes accurately. This study compared 3 common methods of determining orbital volume and sought to identify an accurate, practical manner for doing so. METHODS: The volume of 1 orbit of 8 human cadaver heads was independently measured using 3 different methods: 1) CT was performed, and images were analyzed with 3-dimensional (3D) volumetric software; 2) The same orbits were then exenterated and a silicone cast was taken. The cast volumes were measured by water displacement; 3) The orbits were then filled with 1-mm glass beads that were transferred to a graduated cylinder where their volume was determined. The data were analyzed statistically. RESULTS: Intraobserver agreements were good for both beads and casts. Interobserver agreements were good for both beads and CT (p > 0.05). Values obtained using the bead method were equal to values obtained using the cast method (p > 0.05). However, agreement between direct (orbital fillers and casts) and indirect measurements (radiographic techniques) was not satisfactory (p < 0.05). CONCLUSIONS: Independent of method, determining orbital volume is inherently difficult owing to the hyperbolic parabola that is the orbit entrance; all methods require estimation. Glass beads and casts yielded more reproducible values but can only be used in cadavers. CT measurement is prone to error due to the variability of methodologies used but allows access to enormous testing populations. Interstudy comparison is currently not possible. CT volumetric software with strict universal standards for estimating the anterior limit of the orbit appears to be the best method of studying human orbital volumes.
A 44-year-old man with neurofibromatosis type 1 had been aware that his right eye pulsated. His visual acuity was 20/15 in both eyes and his intraocular pressures were normal. He had 4 mm of right exophthalmos and there was pulse-synchronous pulsation of the right eye (video on the Neurology® Web site at www.neurology.org). No bruit was heard. Lisch nodules were present on both irides. CT showed a large osseous defect of the greater wing of the right sphenoid bone. The differential diagnosis of pulsatile proptosis includes absence of the sphenoid wing in patients with neurofibromatosis 1,(1) carotid-cavernous fistula, orbital roof fractures, and arteriovenous malformations.(2.)
Corneal transplantation is among the most successful solid organ transplants. However, despite low rejection rates of grafts in the 'low-risk' setting, rejection can be as high as 70% when grafted into 'high-risk' recipient beds. Under normal homeostatic conditions, the avascular cornea provides a unique environment that facilitates immune and angiogenic privilege. An imbalance in pro-inflammatory, angiogenic and lymphangiogenic mediators leads to a breakdown in corneal immune privilege with a consequent host response against the donor graft. Recent developments in lamellar and endothelial keratoplasties have reduced the rates of graft rejection even more, while providing improved visual outcomes. The corneal layer against which an immune response is initiated, largely determines reversibility of the acute episode. While epithelial and stromal graft rejection may be treated with topical corticosteroids with higher success, acute endothelial rejection mandates a more aggressive approach to therapy due to the lack of regenerative capacity of this layer. However, current immunosuppressive regimens come with the caveat of ocular and systemic side effects, making prolonged aggressive treatment undesirable. With the advent of biologics, efficacious therapies with a superior side effect profile are on the horizon. In our review we discuss the mediators of ocular immune privilege, the roles of cellular and molecular immune players in graft rejection, with a focus on human leukocyte antigen and antigen presenting cells. Furthermore, we discuss the clinical risk factors for graft rejection and compare rates of rejection in lamellar and endothelial keratoplasties to traditional penetrating keratoplasty. Lastly, we present the current and upcoming measures of therapeutic strategies to manage and treat graft rejection, including an overview of biologics and small molecule therapy.
Genes within the E3 transcription unit of human adenoviruses modulate host immune responses to infection. A comprehensive genomics and bioinformatics analysis of the E3 transcription unit for 38 viruses within human adenovirus species D (HAdV-D) revealed distinct and surprising patterns of homologous recombination. Homologous recombination was identified in open reading frames for E3 CR1α, CR1β, and CR1γ, similar to that previously observed with genes encoding the three major structural capsid proteins, the penton base, hexon, and fiber.
OBJECTIVE: Vascular endothelial cells (ECs) are continuously exposed to blood flow that contributes to the maintenance of vessel structure and function; however, the effect of hemodynamic forces on transforming growth factor-β (TGF-β) signaling in the endothelium is poorly described. We examined the potential role of TGF-β signaling in mediating the protective effects of shear stress on ECs. APPROACH AND RESULTS: Human umbilical vein ECs (HUVECs) exposed to shear stress were compared with cells grown under static conditions. Signaling through the TGF-β receptor ALK5 was inhibited with SB525334. Cells were examined for morphological changes and harvested for analysis by real-time polymerase chain reaction, Western blot analysis, apoptosis, proliferation, and immunocytochemistry. Shear stress resulted in ALK5-dependent alignment of HUVECs as well as attenuation of apoptosis and proliferation compared with static controls. Shear stress led to an ALK5-dependent increase in TGF-β3 and Krüppel-like factor 2, phosphorylation of endothelial NO synthase, and NO release. Addition of the NO donor S-nitroso-N-acetylpenicillamine rescued the cells from apoptosis attributable to ALK5 inhibition under shear stress. Knockdown of TGF-β3, but not TGF-β1, disrupted the HUVEC monolayer and prevented the induction of Krüppel-like factor 2 by shear. CONCLUSIONS: Shear stress of HUVECs induces TGF-β3 signaling and subsequent activation of Krüppel-like factor 2 and NO, and represents a novel role for TGF-β3 in the maintenance of HUVEC homeostasis in a hemodynamic environment.
PURPOSE: To report the features of the rare and under-recognized condition of canaliculops (or canaliculocele) of the eyelid, which is a dilation of the canaliculus, and to evaluate treatment with marsupialization. DESIGN: Retrospective interventional case series. METHODS: The records of 2 patients with canaliculops from the Massachusetts Eye and Ear Infirmary were reviewed. Data collected included clinical history, surgical technique, histopathologic analysis, and comparative immunohistochemical analysis of a range of cytokeratins in normal conjunctival epithelium, normal canalicular epithelium, and canaliculops epithelium. RESULTS: Two women, 53 and 66 years of age, experienced chronic, noninflammatory, painless medial eyelid and eyelid margin fluctuant swelling after earlier trauma or eyelid surgery. The external mass was accompanied by a whitish opalescent or bluish discoloration of a palpebral surface bulge. Biopsy revealed multilaminar (up to 12 cells thick), nonkeratinizing, tightly packed small squamous epithelial cells that surmounted a highly regimented basal layer with a picket fence arrangement. No goblet cells or subepithelial inflammation were present. Immunohistochemistry revealed only superficial CK7 immunostaining and positive patchy suprabasilar CK17 staining in the canaliculops epithelium, contrasting with their full-thickness positivity and negativity, respectively, in normal conjunctival epithelium. Marsupialization achieved resolution of the condition in each patient. CONCLUSIONS: An improved awareness of the normal canalicular epithelial structure and its immunohistochemical features can definitively separate canaliculops from conjunctival cysts. Previous treatment of canaliculops has involved complete excisions. Canaliculops may, however, be effectively treated with less invasive marsupialization while obtaining an adequate biopsy specimen for histopathologic diagnosis.