Category: Peer-reviewed

Novel roles for α-crystallins in retinal function and disease

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Publication date: November 2012
Source:Progress in Retinal and Eye Research, Volume 31, Issue 6
Author(s): Ram Kannan , Parameswaran G. Sreekumar , David R. Hinton
α-Crystallins are key members of the superfamily of small heat shock proteins that have been studied in detail in the ocular lens. Recently, novel functions for α-crystallins have been identified in the retina and in the retinal pigmented epithelium (RPE). αB-Crystallin has been localized to multiple compartments and organelles including mitochondria, golgi apparatus, endoplasmic reticulum and nucleus. α-Crystallins are regulated by oxidative and endoplasmic reticulum stress, and inhibit apoptosis-induced cell death. α-Crystallins interact with a large number of proteins that include other crystallins, and apoptotic, cytoskeletal, inflammatory, signaling, angiogenic, and growth factor molecules. Studies with RPE from αB-crystallin deficient mice have shown that αB-crystallin supports retinal and choroidal angiogenesis through its interaction with vascular endothelial growth factor. αB-Crystallin has also been shown to have novel functions in the extracellular space. In RPE, αB-crystallin is released from the apical surface in exosomes where it accumulates in the interphotoreceptor matrix and may function to protect neighboring cells. In other systems administration of exogenous recombinant αB-crystallin has been shown to be anti-inflammatory. Another newly described function of αB-crystallin is its ability to inhibit β-amyloid fibril formation. α-Crystallin minichaperone peptides have been identified that elicit anti-apoptotic function in addition to being efficient chaperones. Generation of liposomal particles and other modes of nanoencapsulation of these minipeptides could offer great therapeutic advantage in ocular delivery for a wide variety of retinal degenerative, inflammatory and vascular diseases including age-related macular degeneration and diabetic retinopathy.

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The complex interactions of retinal, optical and environmental factors in myopia aetiology

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Publication date: November 2012
Source:Progress in Retinal and Eye Research, Volume 31, Issue 6
Author(s): D.I. Flitcroft
Myopia is the commonest ocular abnormality but as a research topic remains at the margins of mainstream ophthalmology. The concept that most myopes fall into the category of ‘physiological myopia’ undoubtedly contributes to this position. Yet detailed analysis of epidemiological data linking myopia with a range of ocular pathologies from glaucoma to retinal detachment demonstrates statistically significant disease association in the 0 to −6 D range of ‘physiological myopia’. The calculated risks from myopia are comparable to those between hypertension, smoking and cardiovascular disease. In the case of myopic maculopathy and retinal detachment the risks are an order of magnitude greater. This finding highlights the potential benefits of interventions that can limit or prevent myopia progression.Our understanding of the regulatory processes that guide an eye to emmetropia and, conversely how the failure of such mechanisms can lead to refractive errors, is certainly incomplete but has grown enormously in the last few decades. Animal studies, observational clinical studies and more recently randomized clinical trials have demonstrated that the retinal image can influence the eye’s growth. To date human intervention trials in myopia progression using optical means have had limited success but have been designed on the basis of simple hypotheses regarding the amount of defocus at the fovea.Recent animal studies, backed by observational clinical studies, have revealed that the mechanisms of optically guided eye growth are influenced by the retinal image across a wide area of the retina and not solely the fovea. Such results necessitate a fundamental shift in how refractive errors are defined. In the context of understanding eye growth a single sphero-cylindrical definition of foveal refraction is insufficient. Instead refractive error must be considered across the curved surface of the retina. This carries the consequence that local retinal image defocus can only be determined once the 3D structure of the viewed scene, off axis performance of the eye and eye shape has been accurately defined. This, in turn, introduces an under-appreciated level of complexity and interaction between the environment, ocular optics and eye shape that needs to be considered when planning and interpreting the results of clinical trials on myopia prevention.

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Deep Anterior Lamellar Keratoplasty versus Penetrating Keratoplasty for Macular Corneal Dystrophy: A Randomized Trial – Corrected Proof

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Purpose: To compare outcomes of big-bubble deep anterior lamellar keratoplasty (DALK) and penetrating keratoplasty (PK) for macular corneal dystrophy.Design: Prospective, randomized, interventional case series.Methods: setting: Single hospital. patients: Eighty-two eyes of 54 patients requiring keratoplasty for the treatment of macular corneal dystrophy without endothelial involvement were included. main outcome measures: Operative complications, uncorrected visual acuity, best-corrected visual acuity, contrast sensitivity function, higher-order aberrations, and endothelial cell density were evaluated.Results: The DALK and PK group consisted of 35 and 41 eyes, respectively. Best-corrected visual acuity after surgery was 20/40 or better 68.5% and 70.7% of the eyes in the DALK and PK groups, respectively (P > .05). No statistically significant differences between groups were found in contrast sensitivity function with and without glare for any spatial frequency (P > .05). Significantly higher levels of higher-order aberrations were found in the DALK group (P < .01). In both groups, a progressive and statistically significant reduction in endothelial cell density was found (P < .01). At the last follow-up, the mean endothelial cell loss was 18.1% and 26.9% in DALK and PK groups, respectively (P = .03). Graft rejection episodes were seen in 5 eyes (12.1%) in the PK group, and regrafting was necessary in 3 eyes (7.3%). Recurrence of the disease was documented in 5.7% and 4.8% of the eyes in the DALK and PK groups, respectively.Conclusions: Deep anterior lamellar keratoplasty with the big-bubble technique provided comparable visual and optical results as PK and resulted in less endothelial damage, as well as eliminating endothelial rejection in macular corneal dystrophy. Deep anterior lamellar keratoplasty surgery is a viable option for macular corneal dystrophy without endothelial involvement.

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Role of Oral Corticosteroids in Orbital Cellulitis – Corrected Proof

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Purpose: To evaluate the role of oral corticosteroids as an anti-inflammatory adjunct in the treatment of orbital cellulitis.Design: Prospective, comparative, single-masked, interventional clinical study.Methods: setting: Tertiary eye care center (All India Institute of Medical Sciences). study population: Patients with acute onset (within 14 days) of orbital cellulitis with or without abscess. intervention: Patients were randomized into 2 groups in the ratio of 1:2. Both groups received initial intravenous antibiotics. In Group 2, oral steroids were added after an initial response to intravenous antibiotics. main outcome measures: Resolution of signs and symptoms, duration of intravenous antibiotics, length of hospital stay, and sequelae of disease (ptosis, proptosis, and movement restriction) were evaluated and compared between the 2 groups.Results: A total of 21 patients (age range, 11-59 years) with orbital cellulitis were studied. There were 7 patients in Group 1, who received standard intravenous antibiotics, and 14 in Group 2, who received adjuvant steroids. Patients in Group 2 showed an earlier resolution of inflammation in terms of periorbital edema (P = .002 at day 7), conjunctival chemosis (P < .001 at day 10), and pain (P = .012 at day 7). They also attained vision of 0.02 on logMAR earlier than Group 1 patients. Decrease in proptosis and improvement in extraocular movements were also significantly better with the use of steroids (P = .027 at day 10, P = .003 at day 14, respectively). While a significant number of patients in Group 1 had mild residual ptosis, proptosis, and movement restriction at 12 weeks, none of the patients treated with steroids had any residual changes (P = .023, P = .001, and P = .001, respectively). The durations of intravenous antibiotics and hospital stay were significantly less in Group 2.Conclusion: Use of oral steroids as an adjunct to intravenous antibiotic therapy for orbital cellulitis may hasten resolution of inflammation with a low risk of exacerbating infection.

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Interleukin 21, Interleukin 23, and Transforming Growth Factor β1 in HLA-A29-Associated Birdshot Retinochoroidopathy – Corrected Proof

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Purpose: To determine the peripheral levels of 20 immune mediators in serum samples from patients with birdshot retinochoroidopathy (BSRC).Design: Single-center prospective case-control study.Methods: The serum of 17 BSRC patients during different phases of disease activity and therapy were analyzed with a quantitative multiplex sandwich enzyme-linked immunosorbent assay–based microarray to determine the levels of 20 immune mediators (T cell and proinflammatory). The serum of 12 healthy volunteers was used as controls.Results: Serum levels of interleukin (IL)-21 (P = .0005), IL-23 (P = .0005), and transforming growth factor (TGF)-β1 (P = .0011) were elevated in BSRC patients with active disease naïve to systemic therapy compared with that of controls. There was no significant difference in the serum levels of immune mediators between controls and BSRC patients who had a current or past history of IMT or who were in remission. The levels of IL-21, IL-23, and TGF-β1 were positively correlated (IL-23/IL-21, r = 0.91; TGF-β1/IL-21, r = 0.97; TGF-β1/IL-23, r = 0.87; for all, P < .0001).Conclusions: BSRC patients with active disease naïve to systemic therapy have elevated serum levels of 3 key immune mediators known to promote T helper 17 (Th17) cells in autoimmune disease. Our results suggest that IL-21, IL-23, and TGF-β1 may play an important role in the development of site-specific Th17 cell–mediated inflammation in BSRC, which underscore the importance of systemic therapy and offer new insights into the potential of targeted treatments.

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Publication Times, Impact Factors, and Advance Online Publication in Ophthalmology Journals – Corrected Proof

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Objective: Publication speed of peer-reviewed journals may play a major role in early dissemination of knowledge and may raise the citation index. In this study, we evaluated the publication speed of ophthalmology journals.Design: Observational study.Participants: Observational study of bibliometric data in published ophthalmology journals.Methods: A list of ophthalmic journals featured in the 2010 Journal Citation Report was obtained on September 1, 2011. A total of 12 articles were chosen randomly from each of these journals published between January and December 2010. Median publication time and interquartile range (IQR) were obtained from the full texts of the published articles.Main Outcome Measures: Time lag between submission and revision, acceptance, and publication of the manuscripts was calculated. Correlation between publication time lag and journal impact factor as well as advance online publication was analyzed.Results: A total of 51 ophthalmic journals were included. There was no statistically significant difference in the impact factors of journals based on their reporting of submission, revision, or acceptance times of the manuscripts (both P>0.05, Wilcoxon test). The median peer review and publication time of all ophthalmology journals was 133 days (IQR, 100.5–171.5) and 100 days (IQR, 62.9–166.3), respectively. There was no correlation between the journal impact factors and publication time lag (Spearman correlation). Approximately half of the ophthalmology journals (n = 26; 50.98%) published online in advance. Journals with advance online publication had higher impact factors compared with those without this feature (median, 1.692 [IQR, 1.05–2.80] vs. 1.02 [0.39–1.53]; P = 0.015, Mann–Whitney U test). For journals with advance online publication, the median time from acceptance to advance online publication (74.3 days [IQR, 48.3–115 days]) was significantly shorter than the median time between acceptance and print publication (170.75 days [IQR, 101.4–217 days]; P<0.001, Wilcoxon test).Conclusions: Publication time lag in ophthalmology journals was not correlated with journal impact factors. Advance online publication facility was provided by only half of the ophthalmology journals published in 2010. Journals with advance online publication had a higher impact factor compared with those without this feature.Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

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Visual Outcomes after Blunt Ocular Trauma – Corrected Proof

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Objective: To describe the prognosis and retinal location in patients presenting with acute traumatic maculopathy and extramacular retinal injuries.Design: Retrospective, noninterventional case series.Participants and Controls: All patients presenting with commotio retinae or sclopetaria retinae to the Birmingham Midland Eye Centre Eye Casualty from October 1, 2007, to February 23, 2011.Methods: The notes of all patients presenting with ocular trauma in the specified time period were examined to identify suitable patients and demographic and injury data were extracted.Main Outcome Measures: Outcome was assessed by visual acuity (VA).Results: For macular commotio retinae, 53 patients were identified, of whom 34 had adequate follow-up to determine final VA. The median presenting VA was 20/40; 25 patients (74%) recovered to ≥20/30. The median extent of visual recovery was 0.18 logarithm of the minimum angle of resolution (logMAR). For extramacular commotio retinae, 117 patients were identified, of whom 58 had adequate follow-up to determine final VA. The median presenting VA retinae was 20/30; 55 patients (95%) recovered to ≥20/30. The median extent of visual recovery was logMAR 0.076. There was 1 case of extramacular sclopetaria retinae. The 3 most common retinal locations of extramacular commotio retinae, in order of frequency, were inferotemporal (37%), temporal (17%), and superotemporal (17%); <5% of cases were in a nasal location.Conclusions: This is the first report on the prognosis of acute traumatic maculopathy and extramacular commotio retinae. After macular injury, 26% of patients were left with a VA of ≤20/30, although the proportion with visual impairment is higher than this because (1) a deterioration from 20/15 to 20/30 is significant to many patients; and (2) additional patients are visually impaired by symptomatic paracentral visual field defects despite a normal VA. Reduced VA after extramacular commotio retinae may represent occult macular injury or previously undiagnosed visual impairment in the affected eye. Extramacular commotio occurs mostly in an inferotemporal to temporal location, consistent with direct trauma to the sclera overlying the injured retina.Financial Disclosure(s): The authors have no proprietary or commercial interest in any of the materials discussed in this article.

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Near-infrared and Short-wavelength Autofluorescence in Resolved Central Serous Chorioretinopathy: Association With Outer Retinal Layer Abnormalities – Corrected Proof

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Purpose: To evaluate the correlation between changes in fundus autofluorescence (AF) measured using 2 different sources (near-infrared fundus autofluorescence from melanin and short-wavelength fundus autofluorescence from lipofuscin) with changes in spectral-domain optical coherence tomography (SD OCT) and fluorescein angiography in resolved central serous chorioretinopathy (CSC).Design: Retrospective, observational case study.Methods: A total of 91 eyes from 86 patients with a history of resolved CSC and abnormal AF imaging findings were included. In addition to AF, patients were assessed by means of SD OCT and fluorescein angiography. Outer retinal layer alterations in OCT images and abnormalities in fluorescein angiography were analyzed and correlated with the corresponding AF data.Results: All eyes with abnormal near-infrared AF showed a hyperfluorescent angiography window defect in the corresponding area. There was a significant association between the OCT and short-wavelength AF findings. An abnormal short-wavelength AF signal was significantly associated with loss of the ellipsoid portion of the inner segments (EPIS, previously known as the junction between the inner and outer segments of the photoreceptors) on SD OCT (χ2 test; P < .0001). Near-infrared AF could not predict the status of EPIS without the short-wavelength AF image.Conclusions: Outer retinal layer changes in OCT images can be predicted by analyzing both short-wavelength AF and near-infrared AF images. Abnormal changes in the short-wavelength AF image were predictive of EPIS damage.

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