Purpose: Proliferative vitreoretinopathy (PVR) occurs in 5%–10% of rhegmatogenous retinal detachment cases and is the principle cause for failure of retinal reattachment surgery. Although there are a number of surgical adjunctive agents available for preventing the development of PVR, all have limited efficacy. Discovering predictive molecular biomarkers to determine the probability of PVR development after retinal reattachment surgery will allow better patient stratification for more targeted drug evaluations. Methods: Narrative literature review. Results: We provide a summary of the inflammatory and fibrogenic factors found in ocular fluid samples during the development of retinal detachment and PVR and discuss their possible use as molecular PVR predictive biomarkers. Conclusions: Studies monitoring the levels of the above factors have found that few if any have predictive biomarker value, suggesting that widening the phenotype of potential factors and a combinatorial approach are required to determine predictive biomarkers for PVR. Translational Relevance: The identification of relevant biomarkers relies on an understanding of disease signaling pathways derived from basic science research. We discuss the extent to which those molecules identified as biomarkers and predictors of PVR relate to disease pathogenesis and could function as useful disease predictors. (http://www.umin.ac.jp/ctr/ number, UMIN000005604)

Assessment and maintenance of end-organ perfusion are key to resuscitation in critical illness, although there are limited direct methods or proxy measures to assess cerebral perfusion. Novel non-invasive methods of monitoring microcirculation in critically ill patients offer the potential for real-time updates to improve patient outcomes. Parallel mechanisms autoregulate retinal and cerebral microcirculation to maintain blood flow to meet metabolic demands across a range of perfusion pressures. Cerebral blood flow (CBF) is reduced and autoregulation impaired in sepsis, but current methods to image CBF do not reproducibly assess the microcirculation. Peripheral microcirculatory blood flow may be imaged in sublingual and conjunctival mucosa and is impaired in sepsis. Retinal microcirculation can be directly imaged by optical coherence tomography angiography (OCTA) during perfusion-deficit states such as sepsis, and other systemic haemodynamic disturbances such as acute coronary syndrome, and systemic inflammatory conditions such as inflammatory bowel disease. Monitoring microcirculatory flow offers the potential to enhance monitoring in the care of critically ill patients, and imaging retinal blood flow during critical illness offers a potential biomarker for cerebral microcirculatory perfusion.

Background/Aim Historic data suggest that open globe injuries should be repaired within 12–24 hours to reduce the risk of endophthalmitis. However, endophthalmitis is uncommon when systemic antibiotic prophylaxis is given. It is not clear whether delayed primary repair impacts visual outcomes in other ways or what is the optimum time to repair. We aimed to examine the effect of time to primary repair on visual outcomes. Methods This is a retrospective comparative case series including all open globe injuries presenting to the Birmingham Midland Eye Centre between 1 January 2014 and 15 March 2016. Presenting features, mechanism of injury, visual acuity at 6–12 months and demographic data were examined. Results 56 open globe injuries were repaired, of which sufficient data for analysis were available on 52 cases. The mean time to primary repair was 1 day after injury (range 5 hours to 7 days). Final visual acuity at 6–12 months was related to the presenting visual acuity and the Ocular Trauma Score and to the time between injury and primary repair, with a reduction in predicted visual acuity of logarithm of the minimum angle of resolution of 0.37 for every 24 hours of delay (95% CI 0.14 to 0.6). Discussion Open globe injuries should be repaired promptly. Presenting visual acuity remains the strongest predictor of outcome; however, delay to primary repair also reduced final visual acuity, and any significant delay from injury to repair is likely to negatively impact final visual outcome.

Open globe injuries are a significant global cause of visual loss, including unilateral and bilateral blindness. Prognosis is predicted by injury severity, with lower presenting visual acuity and more posterior injuries associated with poor visual outcomes, although even the most severely injured eyes with no perception of light vision may regain some visual function. In addition to severity of the primary injury, the secondary injuries and complications causing poor outcomes include proliferative vitreoretinopathy (PVR) and endophthalmitis. Endophthalmitis is common after open globe injury, affecting up to 16.5% of patients. Systemic antibiotic prophylaxis is commonly used, with a limited evidence base, while intraocular antibiotics are less commonly used but have stronger supporting evidence of efficacy. Endophthalmitis rates are also reduced by prompt primary repair, which may also support recovery of visual acuity. PVR is not prevented or treated by any pharmacologic interventions in current clinical practice, but the incidence of post-traumatic PVR may be reduced by early vitrectomy within the first 4–7 days after injury. Ocular trauma training is often limited in Western ophthalmic surgical training programmes, and patients with ocular trauma often require the input of multiple subspecialists. In this context, it is important that patients have an overview and coordination of the different aspects of their care, with ownership by one lead clinician.

Background: Traumatic optic neuropathy is classically described in up to 8% of patients with traumatic brain injury (TBI), but subclinical or undiagnosed optic nerve damage is much more common. When more sensitive testing is performed, at least half of patients with moderate to severe TBI demonstrate visual field defects or optic atrophy on examination with optical coherence tomography. Acute optic nerve compression and ischaemia in orbital compartment syndrome require urgent surgical and medical intervention to lower the intraocular pressure and diminish the risk of permanent optic nerve dysfunction. Other manifestations of traumatic optic neuropathy have more variable treatments in international practice. Methods: We conducted a systematic review of traumatic optic neuropathy treatments in accordance with the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) statement. Results: We included three randomised controlled trials of intravenous methylprednisolone (IVMP), erythropoietin, and levodopa-carbidopa combination, with no evidence of benefit for any treatment. In addition, large studies in TBI have found strong evidence of increased mortality in patients treated with megadose IVMP. Conclusions: There is therefore no evidence of benefit for any medical treatment and strong evidence of harm from IVMP. There is also no evidence of benefit for optic canal decompression for traumatic optic neuropathy. Orbital compartment syndrome is a separate entity that requires both medical and surgical interventions to prevent visual loss.

Drug delivery by topical application has higher patient acceptance and lower morbidity than intraocular injection, but many ophthalmic treatments are unable to enter the eye or reach the posterior segment after topical application. The first stage towards posterior segment delivery after topical application is ocular surface penetration and existing models are in vivo or use large quantities of tissue. We therefore developed a novel ex vivo model using discs of porcine and human cornea and sclera (5 mm diameter) to assess penetration of a candidate neuroprotective siRNA. siRNA against caspase 2 or control solutions of known penetrance were applied to the corneal epithelial surface and trans-corneal penetration and corneal adsorbance measured at fixed time points. To demonstrate that leakage did not occur, we applied dextran blue, which should not penetrate the intact cornea and did not do so in our model. Fluorescein penetration (0.09%) was less than rhodamine B (6.98%) at 60 min. siCASP2 penetration was 0.01% by 60 min. When the applied siCASP2 was washed off after 2 min, (representing lacrimal drainage) 0.071% penetrated porcine cornea by 60 min and 0.0002% penetrated human cornea and 0.001% penetrated human sclera. Our ex vivo model rapidly and cost-effectively assesses transcorneal penetration of candidate topical therapies, allowing rates of trans-corneal penetration for potential therapies such as siRNA to be evaluated with small quantities of human or animal tissue.