Richard J Blanch

Ophthalmic injuries in British Armed Forces in Iraq and Afghanistan

AimBritish military ophthalmologists have not been deployed in support of operations since 2003. Eye injuries in British forces receive definitive treatment on return to the United Kingdom. We report the injury patterns, management strategies, and outcomes for eye injuries in British Armed Forces in Iraq and Afghanistan.MethodsRetrospective consecutive case series of eye injuries in British Armed Forces in Iraq or Afghanistan from July 2004 to May 2008. Outcomes assessed by final best-corrected visual acuity (VA; few patients lost to follow-up), rates of endophthalmitis, and proliferative vitreoretinopathy (PVR).ResultsThere were 630 cases of major trauma, 63 sustained eye injuries (10%), and 48 sustained significant eye injuries. There were 21 open-globe injuries: 9 ruptures and perforating injuries, of which 7 were enucleated/eviscerated; 11 intraocular foreign body (IOFB) injuries, of which 1 was eviscerated. Primary repair was combined with posterior segment reconstruction in 9/11 cases with IOFB. Mean time to primary repair was 1.9 days (range 0–5). Intravitreal antibiotics were given at primary repair in five cases. All cases received early broad-spectrum systemic antibiotics. Median final VA was logMAR 0.25 excluding evisceration/enucleations. There were two cases of PVR and none of endophthalmitis.ConclusionsThe number of eye injuries as a proportion of all casualties is lower than recently reported. The injuries are more severe than in civilian practise. The outcomes were comparable with previous reports, this demonstrates that, in certain cases, primary repair can be safely delayed beyond 24 h in the patients best interests, in order to optimise the conditions for treatment.

Animal models of retinal injury.

Retinal injury is a common cause of profound and intractable loss of vision. Clinical outcomes are poor in both open and closed globe injuries because cell death, scarring, and a failure of tissue and axon regeneration are not ameliorated by current treatments. Much animal research is directed at understanding and modifying these pathologies, although results have yet to translate into clinical practice. Axotomy-induced retinal ganglion cell (RGC) death in mammals can be effectively reduced and axon regeneration enhanced over the short term. After retinal injury in mammals, the retinal pigment epithelium (RPE) and retinal glia either regenerate lost RPE and neuroretinal cells or form nonfunctional scars. An understanding of the mechanisms underlying injury responses is critical to the successful development of therapeutic strategies to promote ocular repair.

Mesenchymal stromal cell-mediated neuroprotection and functional preservation of retinal ganglion cells in a rodent model of glaucoma.

BACKGROUND AIMS Glaucoma is a leading cause of irreversible blindness involving loss of retinal ganglion cells (RGC). Mesenchymal stromal cells (MSC) have shown promise as a paracrine-mediated therapy for compromised neurons. It is, however, unknown whether dental pulp stem cells (DPSC) are effective as a cellular therapy in glaucoma and how their hypothesized influence compares with other more widely researched MSC sources. The present study aimed to compare the efficacy of adipose-derived stem cells, bone marrow-derived MSC (BMSC) and DPSC in preventing the loss of RGC and visual function when transplanted into the vitreous of glaucomatous rodent eyes. METHODS Thirty-five days after raised intraocular pressure (IOP) and intravitreal stem cell transplantation, Brn3a(+) RGC numbers, retinal nerve fibre layer thickness (RNFL) and RGC function were evaluated by immunohistochemistry, optical coherence tomography and electroretinography, respectively. RESULTS Control glaucomatous eyes that were sham-treated with heat-killed DPSC had a significant loss of RGC numbers, RNFL thickness and function compared with intact eyes. BMSC and, to a greater extent, DPSC provided significant protection from RGC loss and RNFL thinning and preserved RGC function. DISCUSSION The study supports the use of DPSC as a neuroprotective cellular therapy in retinal degenerative disease such as glaucoma.

Visual Outcomes after Blunt Ocular Trauma

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.

Military ocular injury: presentation, assessment and management.

Visual loss magnifies the significance of an ocular injury, because it is likely to lead to loss of career, major lifestyle changes and disfigurement. Unlike in peacetime where unilateral injuries are the rule, ocular war injuries are bilateral in 15–25% of cases [1,2]. The use of body armour in warfare makes explosive injuries more survivable, but leave the face and eyes relatively exposed. Though the eyes occupy 0.1% of the total and 0.27% of the anterior surface of the body, they are disproportionately affected in explosive injuries. The development of weapons with higher explosive and fragmentation power has led to a continuous increase in the proportion of eye injuries over the years (Table 1). Over the past 40 years this proportion has risen to between 5 and 7% in the three Arab-Israeli conflicts, attributed to the preponderance of urban and tank warfare [1,2]. Continued urbanisation of warfare, increased explosive power of weapons and poor uptake of ocular protection contributed to further increases; 13% in Operation Desert Storm (1991) [3]. Prioritisation of combat eye protection may have contributed to the reduction of the proportion of eye injuries to 4.87% in American Operations in Iraq (2003-2005) [4].

Neuroretinal cell death in a murine model of closed globe injury: pathological and functional characterization.

PURPOSE Blunt ocular trauma causes severe retinal injury with death of neuroretinal tissue, scarring, and permanent visual loss. The mechanisms of cell death are not known, and there are no therapeutic interventions that improve visual outcome. We aimed to study the extent, distribution, and functional consequences of cell death by developing and characterizing a rat model of retinal injury caused by blunt ocular trauma. METHODS The eyes of anesthetized adult rats were injured by either weight drop or low-velocity ballistic trauma and assessed by clinical examination, electroretinography, light microscopy, electron microscopy, and TUNEL. Projectile velocity was measured and standardized. RESULTS Weight drop did not cause reproducible retinal injury, and the energy threshold for retinal injury was similar to that for rupture. Low-velocity ballistic trauma to the inferior sclera created a reproducible retinal injury, with central sclopetaria retinae, retinal necrosis, and surrounding commotio retinae with specific photoreceptor cell death and sparing of cells in the other retinal layers. The extent of photoreceptor cell death declined and necrosis progressed to apoptosis with increasing distance from the impact site. CONCLUSIONS This is the only murine model of closed globe injury and the only model of retinal trauma with specific photoreceptor cell death. The clinical appearance mirrors that in severe retinal injury after blunt ocular trauma in humans, and the ultrastructural features are consistent with human and animal studies of commotio retinae. After ocular trauma, photoreceptor apoptosis may be prevented and visual outcomes improved by blocking of the cell death pathways.

Decorin Reduces Intraocular Pressure and Retinal Ganglion Cell Loss in Rodents Through Fibrolysis of the Scarred Trabecular Meshwork

PURPOSE To investigate whether Decorin, a matrikine that regulates extracellular matrix (ECM) deposition, can reverse established trabecular meshwork (TM) fibrosis, lower IOP, and reduce progressive retinal ganglion cell (RGC) death in a novel rodent model of TM fibrosis. METHODS Adult rats had intracameral (IC) injections of human recombinant (hr) TGF-β over 30 days (30 d; to induce TM fibrosis, raise IOP, and initiate RGC death by 17 d) or PBS (controls) and visually evoked potentials (VEP) were measured at 30 d to evaluate resultant visual pathway dysfunction. In some animals TGF-β injections were stopped at 17 d when TM fibrosis and IOP were consistently raised and either hrDecorin or PBS IC injections were administered between 21 d and 30 d. Intraocular pressure was measured biweekly and eyes were processed for immunohistochemical analysis of ECM deposition to assess TM fibrosis and levels of matrix metalloproteinases (MMP) and tissue inhibitors of matrix metalloproteinases (TIMP) to assess fibrolysis. The effect of hrDecorin treatment on RGC survival was also assessed. RESULTS Transforming growth factor-β injections caused sustained increases in ECM deposition in the TM and raised IOP by 17 d, responses that were associated with 42% RGC loss and a significant decrease in VEP amplitude measured at 30 d. Decorin treatment from 17 d reduced TGF-β-induced TM fibrosis, increased levels of MMP2 and MMP9 and lowered TIMP2 levels, and lowered IOP, preventing progressive RGC loss. CONCLUSIONS Human recombinant Decorin reversed established TM fibrosis and lowered IOP, thereby rescuing RGC from progressive death. These data provide evidence for the candidacy of hrDecorin as a treatment for open-angle glaucoma.

Caspases in retinal ganglion cell death and axon regeneration

Retinal ganglion cells (RGC) are terminally differentiated CNS neurons that possess limited endogenous regenerative capacity after injury and thus RGC death causes permanent visual loss. RGC die by caspase-dependent mechanisms, including apoptosis, during development, after ocular injury and in progressive degenerative diseases of the eye and optic nerve, such as glaucoma, anterior ischemic optic neuropathy, diabetic retinopathy and multiple sclerosis. Inhibition of caspases through genetic or pharmacological approaches can arrest the apoptotic cascade and protect a proportion of RGC. Novel findings have also highlighted a pyroptotic role of inflammatory caspases in RGC death. In this review, we discuss the molecular signalling mechanisms of apoptotic and inflammatory caspase responses in RGC specifically, their involvement in RGC degeneration and explore their potential as therapeutic targets.

Caspase-9 mediates photoreceptor death after blunt ocular trauma.

PURPOSE Ocular trauma is common in civilian and military populations. Commotio retinae involves acute disruption of photoreceptor outer segments after blunt ocular trauma, with subsequent photoreceptor apoptosis causing permanent visual impairment. The mechanisms of photoreceptor death in commotio retinae have not previously been described, although caspase-dependent death is important in other nontraumatic retinal degenerations. We assessed the role of caspase-9 as a mediator of photoreceptor death in a rat model of ballistic ocular trauma causing commotio retinae. METHODS Bilateral commotio retinae was induced in rats by ballistic ocular trauma. Caspase-9 activity was assessed by immunohistochemistry, Western blotting, and bVAD-fmk active caspase capture. Caspase-9 was inhibited by unilateral intravitreal injection of highly specific X-linked inhibitor of apoptosis (IAP) baculoviral IAP repeat 3 (XBIR3) domain linked to the cell transduction peptide penetratin 1 (Pen-1) after ballistic injury, and the affected eyes were compared with control eyes treated with Pen-1 injection alone, and retinal function was assessed by electroretinogram a-wave amplitude and photoreceptor survival by outer nuclear layer thickness. RESULTS Increased levels of cleaved caspase-9 were shown in photoreceptors 5 hours after injury, and catalytically active full-length caspase-9 was isolated from retinas. Photoreceptor death after commotio retinae was reduced by caspase-9 inhibition by using Pen-1-XBIR3, and electroretinographic measurements of photoreceptor function was preserved, providing structural and functional neuroprotection. CONCLUSIONS The time course of caspase-9 activation and the neuroprotective effects of inhibition suggest that caspase-9 initiates cell death in a proportion of photoreceptors after blunt ocular trauma and that an intravitreally delivered biologic inhibitor may be an effective translational treatment strategy.

Clinical and surgical risk factors in the development of proliferative vitreoretinopathy following retinal detachment surgery: a systematic review protocol

BackgroundProliferative vitreoretinopathy (PVR) is a known complication of retinal detachment surgery. It has been postulated that the establishment of PVR involves inflammatory and ischaemic processes. Surgical and clinical risk factors contribute to making certain patients more vulnerable to developing PVR.The objective of this systematic review is to identify and appraise the evidence on clinical and surgical risk factors and their utility in predicting the occurrence or worsening of PVR post-surgery.MethodsElectronic databases and grey literature will be searched dating from 1980. Studies will be eligible if they include patients that underwent retinal reattachment surgery for rhegmatogenous retinal detachment (RRD), with and without PVR, and where risk factors were measured before or during surgery. Screening, data extraction and quality assessment will be performed independently by two reviewers using pre-defined criteria. Should any models be identified, we will liaise with the Cochrane prognostic group to help define the most appropriate quality assessment criteria based on the PROBLAST tool which is in development. All findings will be tabulated and narratively synthesised. Studies presenting models or adjusted data will likely be more informative than studies reporting unadjusted results for a single risk factor. When clinically and methodologically appropriate, random effects meta-analysis will be performed.DiscussionThis review will systematically and comprehensively retrieve evidence to evaluate the clinical and surgical risk factors associated with PVR. The identified evidence may aid standardisation of clinical practice and more effective management for improving patient outcomes following RRD surgery and will provide a clear reference point for vitreoretinal surgeons.Systematic review registrationPROSPERO CRD42016035848