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Purpose of review Retinal detachment initiates a series of events that lead to degenerative changes in retinal synaptic architecture as well as the well-known phenomena of gliosis and photoreceptor apoptosis. Retinal reattachment does not always result in complete visual recovery, even if the fovea is not directly involved in the detachment. Rho-kinase (ROCK) inhibitors may mitigate some of these deleterious changes including disruption of synaptic architecture, photoreceptor apoptosis, and initiation of the epithelial-mesenchymal transition that characterizes proliferative vitreoretinopathy (PVR). This review focuses on the use of ROCK inhibitors to modulate synaptic disjunction. Recent findings ROCK inhibition prevents retinal detachment-induced photoreceptor synaptic terminal retraction (i.e., synaptic disjunction), thereby diminishing the damage of the first synapse in the visual pathway. ROCK inhibition also reduces retinal detachment-induced photoreceptor apoptosis and suppresses PVR progression in preclinical models. Summary Inhibition of ROCK may help to optimize visual recovery after retinal detachment surgery or iatrogenic detachments during cell transplantation or viral subretinal injection and might play a role in reducing the risk of PVR after retinal detachment surgery.

PURPOSE: To evaluate demographic trends of open globe injuries (OGIs) using a large dataset representative of United States population. METHODS: Retrospective cross-sectional observational study using the National Inpatient Sample (NIS) database from 2002 to 2013. Only patients with a primary admitting diagnosis of OGI were included. Data included age (in years), gender, race, type of OGI, death rate and length and cost of stay. RESULTS: During the 12-year period, 27,467 adults (age > 20) with acute OGIs were admitted to the US hospitals. The incidence of OGIs in the adult US population was 10.6 cases per 1,000,000 persons. The mean age was 50.4 years (SD 21.52); the average ages of men and women were 44.34 (SD 17.63) and 65.69 (SD 22.77), respectively. Men accounted for 71% of all cases, with 84% of patients under 60. A decrease in the number of OGIs was seen with advancing age in men, whereas the opposite was true for women. Men, elderly over 80 and Blacks were at the highest risk of sustaining an OGI. The most and least common types of injuries were penetrating injuries (73%) and IOFBs (11%), respectively. Over half of young adults in the 21–40 cohort and 43% of men were uninsured (p

Purpose: The purpose of this study is to describe the patient characteristics, management, and outcomes of bleb-related endophthalmitis (BRE). Methods: A retrospective chart review was conducted of patients who presented to a tertiary care facility from 2001 to 2016 with BRE. Collected data included demographics, medical and ocular history, visual acuity (VA), intraocular pressure (IOP), presence of hypopyon, treatment, microbiology, visual outcomes particularly of VA and IOP, and complications. Results: Thirty-six eyes (36 patients: 21 females, mean 66.8 years old, 78% with primary open-angle glaucoma) presented an average of 4.5 years (range, 2 days-33 years) after glaucoma surgery (30 trabeculectomies with mitomycin C, 6 tube shunts) with endophthalmitis. Mean VA and IOP at presentation were hand motion (HM; logMAR 2.1) and 19.9 mmHg, respectively, with 82% displaying hypopyon and 87% with purulent blebitis. Eighteen (50%) eyes (mean VA HM) underwent vitreous tap and injection (T/I) of intravitreal antibiotics (vancomycin 1 mg/0.1 cc and ceftazidime 2.25 mg/0.1 cc), and 18 (50%) eyes (mean VA HM) underwent pars plana vitrectomy (PPV) with intravitreal antibiotic injection. Eight (45%) eyes initially treated with T/I required a subsequent PPV, and 5 (28%) eyes treated initially with PPV underwent a second PPV. All patients also received systemic antibiotics (33 intravenous [IV] and 3 oral) and topical medications. Average time to documented resolution was 15 days, with mean VA of HM and IOP of 13.6 mmHg. Thirty-one (86%) eyes had vision worse than 20/200 at resolution, and those presenting with light perception or no light perception (NLP) vision (n = 6) had worse vision final VA (logMAR 2.6) than those with initial vision of HM or better (final VA logMAR 1.7). Three (8.6%) eyes were enucleated, with 4 worsening to NLP during the course of the infection. Conclusions: BRE is a visually devastating infection requiring prompt diagnosis and management. Despite aggressive treatment with antibiotics, visual prognosis is poor.

Topic This study evaluated the cardiovascular/cerebrovascular safety profile of ranibizumab 0.5 mg versus sham ± verteporfin in patients with neovascular age-related macular degeneration (nAMD). In addition, comparisons of ranibizumab 0.3 mg with sham and ranibizumab 0.5 mg to 0.3 mg were performed. Clinical Relevance Intravitreal anti–vascular endothelial growth factor (VEGF) agents carry potential increased systemic risks, including cardiovascular or cerebrovascular events. Pooled safety analyses allow better interpretation of safety outcomes seen in individual clinical trials, especially for less common events. To our knowledge, this is the largest patient-level pooled analysis of patients with nAMD treated with ranibizumab. Methods Patient-level pooled analysis of data from 7 Genentech- and Novartis-sponsored phase II, III, and IV studies in nAMD that were completed by December 31, 2013. Pairwise comparisons (primary comparison: ranibizumab 0.5 mg [globally approved dose for nAMD] vs. sham or verteporfin) were performed using Cox proportional hazard regression (hazard ratios [HRs], 95% confidence intervals [CIs]) and rates per 100 patient-years. Standardized Medical Dictionary for Regulatory Activities queries (SMQs) and extended searches were used to identify relevant safety endpoints, including arterial thromboembolic events (ATEs), myocardial infarction (MI), stroke or transient ischemic attack (TIA), stroke (excluding TIA), vascular deaths, and major vascular events as defined by the Antiplatelet Trialists’ Collaboration (APTC). Results The HRs (95% CIs) for the primary comparison of ranibizumab 0.5 mg (n=480) versus sham or verteporfin (n=462) were 1.16 (0.72–1.88) for ATE, 1.33 (0.59–2.97) for MI, 1.43 (0.54–3.77) for stroke excluding TIA, 1.25 (0.61–2.55) for stroke or TIA, 0.57 (0.18–1.78) for vascular death, and 1.12 (0.64–1.98) for APTC events. Hazard ratio 95% CIs included 1, indicating no significant treatment differences, for all endpoints for comparison of ranibizumab 0.5 mg versus sham or verteporfin. Conclusions The rates of cardiovascular and cerebrovascular events were low in these patients with nAMD and not clinically meaningfully different for patients treated with ranibizumab 0.5 mg versus sham or verteporfin, which supports the favorable benefit–risk profile of ranibizumab in the patient population with nAMD. Pooling these studies allows an analysis with higher power and precision compared with individual study analyses.

Purpose: To study the treatment effect of antivascular endothelial growth factor (anti-VEGF) injections on eyes with iris neovascularization (NVI). Methods: Retrospective study of patients who underwent intravitreal anti-VEGF for the treatment of NVI at the Rutgers-Institute of Ophthalmology and Visual Sciences between January 1, 2007 and March 30, 2017. Results: Twenty-eight eyes (mean age, 63 ± 13 years old, 12 [43%] males) were identified. All patients had NVI, and 23 patients had concurrent neovascular glaucoma. The etiology of anterior segment ischemia was proliferative diabetic retinopathy in 20 eyes (71%), central retinal vein occlusion in 7 eyes (25%), and branch retinal vein occlusion in 1 eye (4%). Corneal edema in 25 eyes (89%), hyphema in 11 (39%), visually significant cataract in 25 (86%), and vitreous hemorrhage in 15 (54%) precluded an adequate view to the fundus to perform panretinal photocoagulation (PRP). All patients initially received anti-VEGF therapy; PRP was provided in some eyes ( n = 7) with persistent NVI if the view to the fundus improved. On average, 1.66 (median, 1; standard deviation [SD], 1.64) anti-VEGF injections were performed before complete NVI regression was achieved. Complete regression of rubeosis iridis took an average of 42 (median, 40; SD, 48) days from the first injection. Ten eyes (36%) had recurrence of rubeosis at 198 (median, 126; SD, 165) days after complete regression of NVI. Conclusions: NVI regression was noted in all eyes. Anti-VEGF may be a good supplement for initial NVI management in eyes when PRP cannot be initiated.

Purpose To discuss the potential contribution of rod and cone synapses to the loss of visual function in retinal injury and disease. Methods The published literature and the authors' own work were reviewed. Results Retinal detachment is used as a case study of rod spherule and cone pedicle plasticity after injury. Both rod and cone photoreceptors terminals are damaged after detachment although the structural changes observed are only partially overlapping. For second-order neurons, only those associated with rod spherules respond consistently to injury by remodeling. Examination of signaling pathways involved in plasticity of conventional synapses and in neural development has been and may continue to be productive in discovering novel therapeutic targets. Rho kinase (ROCK) inhibition is an example of therapy that may reduce synaptic damage by preserving normal synaptic structure of rod and cone cells. Conclusions We hypothesize that synaptic damage contributes to poor visual restoration after otherwise successful anatomical repair of retinal detachment. A similar situation may exist for patients with degenerative retinal disease. Thus, synaptic structure and function should be routinely studied, as this information may disclose therapeutic strategies to mitigate visual loss.

Purpose To describe the characteristics of open-globe injuries with posterior segment intraocular foreign bodies (IOFBs). Design Retrospective chart review study. Participants Patients treated for posterior segment IOFB injuries. Methods Retrospective analysis of all patients with posterior segment IOFBs from 2003 to 2014 was conducted. Data including demographics, mechanism of injury, type of IOFB, method of diagnosis, presenting examination, medical and surgical treatment, visual outcomes, and complications were recorded. Main Outcome Measures Visual acuity (VA); anatomically successful retinal reattachment; need for additional surgery; frequency of post-traumatic complications, such as sympathetic ophthalmia (SO), endophthalmitis, and enucleations; and accuracy of Ocular Trauma Score (OTS). Results Thirty-one patients (28 male; mean age, 36.6 years; 42% Hispanic) had posterior segment IOFB injuries, 23 (74%) of which were construction work related. Twenty-five IOFBs (81%) were metallic. Twenty-four IOFBs (77%) had Zone I entry. Computed tomography (CT) scan detected an IOFB in 21 of 22 eyes in which it was performed, with 1 scan highly suspicious for an IOFB. Average size of the IOFB was 10 mm3; size or initial VA did not have any correlation with final VA. The OTS had 60% accuracy in predicting final VA (n = 20). The majority of patients had traumatic cataract and vitreous hemorrhage (VH) on presentation (77% and 61%, respectively); 65% had a retinal tear or retinal detachment (RD), and these patients had worse final VA than those with no retinal pathology. Average time from injury to IOFB removal was 3 days because of the delay in presentation to our facility; 27 of 31 patients (87%) had IOFBs removed within 24 hours of presentation with pars plana vitrectomy (PPV) and either gas or silicone oil tamponade. Patients were admitted for an average of 4 days of intravenous antibiotics. The most common complication was recurrent RD in 11 patients (35%), which portended worse final VA. One patient (3%) developed SO. There were no cases of postoperative endophthalmitis or enucleation. Conclusions Open-globe injuries with posterior segment IOFBs have a guarded visual prognosis, particularly when associated with RD. Increased awareness of the importance of eye protection can help minimize the occurrence of these injuries.

Age-related macular degeneration (AMD) involves progressive degeneration of the central retina, termed the macula, which provides high-acuity vision needed to recognize faces, drive, etc. AMD is the leading cause of blindness in the aging population. A plethora of paradigm-shifting perspectives regarding AMD's multifaceted pathophysiology is emerging. This review will endeavor to gather novel insights and attempts to identify translational implications and new areas of research. The concept of aberrant inflammation being at the center of age-related diseases, particularly AMD, is being received with increasing credence. Retinal angiogenesis, at the forefront of the neovascular complications of AMD (nAMD), is now being understood as an imbalance between trophic factors released by retinal cells secretome. Additionally, mechanisms involving oxidative stress and inflammatory complement pathways have also been identified, along with genetic and other risk factors that play a key role in AMD's onset and progression. Associations have been drawn with AMD and other degenerative deposit diseases such as Alzheimer's disease, atherosclerosis, and glomerulonephritis, which are providing further insight into this maculopathy.

Retinal stem cell therapy is under investigation in several registered phase I/II clinical trials as a potential means to preserve or restore vision in various retinal degenerative conditions such as age-related macular degeneration (AMD), retinitis pigmentosa, and Stargardt macular dystrophy. The therapeutic cellular substrates include retinal pigment epithelium (RPE) cells derived from embryonic stem cells (ESC) or induced pluripotent stem cells (iPSC). Other trials involve the subretinal or intravitreal transplantation of allogeneic cells such as umbilical stem cells and fetal-derived retinal progenitor cells. Delivery methods include cell suspension transplantation or cellular sheet transplantation in which synthetic scaffolds are used to support the cell patch as a preformed monolayer. Overall, encouraging safety data indicate the absence of significant adverse effects related to the cells or scaffolds; however, several safety concerns have arisen from the surgical procedure(s) used for stem cell delivery. Additionally, severe complications have arisen following the delivery of unregulated direct-to-consumer products, and there has been a call for greater regulatory oversight to protect patients. Retinal stem cell therapy holds great promise as a treatment for patients with retinal degenerative diseases. Further development of the various approaches is warranted.

Advantages of the eye as a target organ for cell-based therapy are as follows. The anatomy and physiology of the retina have been characterized in detail. Surgical access to the vitreous cavity and the subretinal space are well established with an excellent safety record. The eye is an immune privileged organ, particularly the subretinal space, which may reduce the need for long-term immune suppression of transplant recipients. High-resolution noninvasive imaging technology permits visualization and functional assessment of the transplanted cells in situ. These imaging and monitoring capabilities permit development of an iterative pathway to successful transplant paradigms in human patients as well as precise modulation of immunotherapy should it be needed.

The availability of noninvasive high-resolution imaging technology, the immune-suppressive nature of the subretinal space, and the existence of surgical techniques that permit transplantation surgery to be a safe procedure all render the eye an ideal organ in which to begin cell-based therapy in the central nervous system. A number of early stage clinical trials are underway to assess the safety and feasibility of cell-based therapy for retinal blindness. Cell-based therapy using embryonic stem cell-derived differentiated cells (e.g., retinal pigment epithelium (RPE)), neural progenitor cells, photoreceptor precursors, and bone marrow-derived hematopoietic stem/progenitor cells has demonstrated successful rescue and/or replacement in preclinical models of human retinal degenerative disease. Additional research is needed to identify the mechanisms that control synapse formation/disjunction (to improve photoreceptor transplant efficacy), to identify factors that limit RPE survival in areas of geographic atrophy (to improve RPE transplant efficacy in eyes with age-related macular degeneration), and to identify factors that regulate immune surveillance of the subretinal space (to improve long-term photoreceptor and RPE transplant survival).

Blockade of vascular endothelial growth factor (VEGF) signaling, whether via sequestration of free VEGF or via inhibition of the tyrosine kinases activated by VEGF, is associated with decreased nitric oxide (NO) and prostaglandin-I 2 (PG-I 2) production along with vascular endothelial cell death. Systemic administration of drugs that block VEGF signaling (eg, for cancer treatment) is associated with systemic complications such as hypertension and thrombosis. Evidence regarding the risk of systemic serious adverse events after intravitreal injection of anti-VEGF agents in patients with diabetic macular edema or neovascular age-related macular degeneration is inconsistent, in part because of study design limitations (eg, bias of ascertainment through strict enrollment criteria and/or inadequate power to identify the risk of low frequency events). Studies involving patients at high risk of arteriothrombotic events (eg, patients with diabetic macular edema) who have high exposure to intravitreal anti-VEGF therapy (eg, monthly aflibercept or ranibizumab injection) demonstrate an increased risk of all-cause mortality compared with randomized controls. The pharmacokinetics of anti-VEGF drug clearance from the systemic circulation and the documented sustained reduction in free plasma VEGF levels after intravitreal aflibercept and bevacizumab injection are consistent with these findings. Although the frequency of systemic serious adverse events after intravitreal anti-VEGF therapy is low, some patients may be at higher risk (eg, those with recent stroke or multiple strokes), and physicians may wish to take special measures with these patients to minimize the risk of systemic complications.

Intraocular foreign body injuries may result in a wide range of intraocular pathology and visual outcomes based on the mechanism of injury, type of foreign body, and subsequent complications. We have reviewed the literature to describe the epidemiology and mechanisms of such injuries; types of foreign bodies; imaging tools for diagnosis; current trends in management, presurgical, and surgical interventions; as well as visual prognosis and potential complications. The purpose of this review is to familiarize clinicians with the recent advances in diagnosis and management of such injuries.

Age-related macular degeneration (AMD) constitutes a prevalent, chronic, and progressive retinal degenerative disease of the macula that affects elderly people and cause central vision impairment. Despite therapeutic advances in the management of neovascular AMD, none of the currently used treatments cures the disease or reverses its course. Medical treatment of neovascular AMD experienced a significant advance due to the introduction of vascular endothelial growth factor inhibitors (anti-VEGF), which dramatically changed the prognosis of the disease. However, although anti-VEGF therapy has become the standard treatment for neovascular AMD, many patients do not respond adequately to this therapy or experience a slow loss of efficacy of anti-VEGF agents after repeated administration. Additionally, current treatment with intravitreal anti-VEGF agents is associated with a significant treatment burden for patients, caregivers, and physicians. New approaches have been proposed for treating neovascular AMD. Among them, designed ankyrin repeat proteins (DARPins) seem to be as effective as monthly ranibizumab, but with greater durability, which may enhance patient compliance with needed injections.

Proliferative diabetic retinopathy (PDR) is a leading cause of vision loss, and it is characterized by retinal neovascularization at the disc (NVD) or elsewhere in the retina (NVE). Panretinal photocoagulation (PRP) has been the standard treatment for PDR for more than four decades. However, this destructive treatment may be associated with several side effects. For this reason, in recent years, new, more selective, laser treatment modalities have been studied in order to maintain efficacy while reducing side effects.

Inherited retinal degenerations (IRDs) represent a diverse group of progressive, visually debilitating diseases that can lead to blindness in which mutations in genes that are critical to retinal function lead to progressive photoreceptor cell death and associated vision loss. IRDs are genetically heterogeneous, with over 260 disease genes identified to date.1 The development of treatments and cures to modify the rate of disease progression has been limited to date, with some success of neurotrophic factor therapy and gene therapies reported from clinical trials.2–11 The best example of treatment success is gene augmentation therapy for IRD caused by mutations in the RPE65 gene, which recently received US Food and Drug Administration (FDA) approval, which in fact represented the first FDA-approved gene therapy (GT) for any genetically inherited disease.4–9 Recent developments in the IRD field have advanced understanding of the mechanisms responsible for vision loss, creating new opportunities to intervene in the course of disease by developing new therapeutic approaches. In 2013, a Delphi-style gathering of IRD experts led to the identification, by consensus, of top priorities to advance therapeutic efforts for IRDs, including the need for systematic genotyping, improved standardization of visual function testing, development of more rigorous and widespread data collection protocols, and increased data sharing.12 This document summarizes more recent advances in the IRD field and outlines specific knowledge gaps. These knowledge gaps present opportunities for further investigation to enable development of therapies that may slow down or prevent vision loss, or restore vision, in affected patients. Atrophic age-related macular degeneration (AMD) is included among the target inherited retinal diseases of interest because first, understanding AMD may contribute to understanding of inherited macular diseases, and second, understanding of the genetics and mechanism of inherited macular degenerations may contribute to understanding of AMD.

To describe characteristics and outcomes of combined pars plana vitrectomy and Baerveldt tube insertion procedure from 2005 to 2010 in eyes with neovascular glaucoma.Seventy-nine patients (89 eyes) with ≥2 months of follow-up were included. Outcome measures were visual acuity, intraocular pressure (IOP), number of glaucoma medications, and complications. Changes in mean logMAR visual acuity, IOP, and glaucoma medications were compared by a two-tailed t-test.Mean patient age was 69.0 years. Forty-three (54%) were male. Mean follow-up time was 19.9 months. Most common causes of neovascular glaucoma was diabetes (n = 63 [71%]) and central retinal vein occlusion (n = 21 [24%]). Eighty-six eyes (97%) underwent a 250 mm Baerveldt drainage device and 3 (3.4%) a 350 mm Baerveldt. Forty-five (51%) 20-gauge, 12 (13%) 23-gauge, and 32 (36%) 25-gauge pars plana vitrectomies were performed. Fifty-two eyes (58%) preoperatively and 23 (33%) postoperatively received intraocular injections for rubeosis and macular edema. Mean ± standard deviation logMAR visual acuity at 18-, 24-, 36-, and 48-month follow-up time points was significantly better than preoperative vision (P0.05). Preoperative versus final IOP and number of glaucoma medications were significantly decreased (P0.05). Fourteen eyes (16%) had a final visual acuity of no light perception. Most common complications included transient ocular hypertension (n = 82 [92%]), transient hypotony (n = 20 [22%]), hyphema (n = 19 [21%]), corneal edema (n = 17 [19%]), and vitreous hemorrhage (n = 14 [16%]). The frequency of transient hypotony, vitreous hemorrhage, and rubeosis was significantly (P0.05) higher in 20-gauge versus 23-/25-gauge pars plana vitrectomy eyes. Nine eyes (10%) required return to the operating room after combined procedure, including 4 eyes (4.5%) for retinal detachment and 3 (3.4%) for high IOP due to tube occlusion. Three eyes (3.4%) developed endophthalmitis and 2 (2.2%) progressed to being pre/phthisical (none were enucleated).Combined pars plana vitrectomy and Baerveldt glaucoma shunt may be a useful procedure in reducing IOP and number of glaucoma medications in eyes with neovascular glaucoma along with stabilizing visual acuity in a majority of these eyes. Further studies are warranted to verify and expand on these findings.

Open globe injury (OGI) is a severe form of eye trauma estimated at 2-3.8/100,000 in the United States. Most pediatric cases occur at home and are the result of sharp object penetration. The aim of this article is to review the epidemiology, diagnosis, management, and prognosis of this condition by conducting a systematic literature search with inclusion of all case series on pediatric OGI published between 1996 and 2015. Diagnosis of OGI is based on patient history and clinical examination supplemented with imaging, especially computed tomography when indicated. Few prospective studies exist for the management of OGI in pediatric patients, but adult recommendations are often followed with success. The main goals of surgical management are to repair the open globe and remove intraocular foreign bodies. Systemic antibiotics are recommended as medical prophylaxis against globe infection, or endophthalmitis. Other complications are similar to those seen in adults, with the added focus of amblyopia therapy in children. Severe vision decline is most likely due to traumatic cataracts. The ocular trauma score, a system devised to predict final visual acuity (VA) in adults, has proven to be of prognostic value in pediatric OGI as well. Factors indicating poor visual prognosis are young age, poor initial VA, posterior eye involvement, long wound length, globe rupture, lens involvement, vitreous hemorrhage, retinal detachment, and endophthalmitis. A thorough understanding of OGI and the key differences in epidemiology, diagnosis, management, and prognosis between adults and children is critical to timely prevention of posttraumatic vision loss early in life.

BACKGROUND:: To describe the demographics, characteristics, and outcomes of open-globe injuries (OGIs) in elderly patients. METHODS:: Retrospective chart review. RESULTS:: Ninety cases (26 men) were identified. The average age was 80 years (range, 65-96 years). The types of OGIs included rupture (83.3%) and penetrating (16.7%) injuries. The causes of trauma were falls (64.4%), accidents (20%), motor vehicle accidents (5.5%), and assault (3.33%). Types of lacerations included corneal (44.4%), corneoscleral (26.7%), and scleral (28.9%). Forty-six cases were OGIs because of dehiscence of previous ocular surgical wound. Ten eyes had concurrent orbital fractures. Approximately 81.1% of cases underwent primary OGI repair within 24 hours of injury, and all cases underwent primary OGI repair within 24 hours of admission. The average visual acuity at presentation was 20/4,375 (SD, 0.64). Although 22 patients presented with no light perception, only 10 remained no light perception after OGI repair. Complications at presentation included uveal prolapse (70%), hemorrhagic choroidal detachment (37.8%), vitreous hemorrhage (51.1%), retinal detachment (20%), and afferent pupillary defect (42.2%). Three patients (3.33%) underwent primary pars plana vitrectomy for retinal detachment and vitreous hemorrhage. Three patients developed endophthalmitis. Overall, retinal attachment was achieved in all eyes that underwent primary pars plana vitrectomy. Primary enucleations were performed in 4 cases (4.44%) for nonsalvageable no light perception eyes. CONCLUSION:: The visual prognosis of OGIs in the elderly population is poor; only 14.4% achieved 20/200 or better visual acuity. Precautionary measures should be taken to prevent OGIs in the elderly population. Language: en

Purpose To summarize major innovations in retinal disease management during fiscal year 2014. Design Literature review. Methods A subset of papers published in the peer-reviewed literature were selected. Results Major innovations in retina include: (1) advances in the treatment of diabetic macular edema, including the use of aflibercept and sustained delivery dexamethasone intravitreal implants as well as subthreshold micropulse diode laser therapy; (2) reduced progression of age-related macular degeneration (AMD) using zinc, vitamin C, vitamin E, lutein, and zeaxanthin supplements as reported in the Age-Related Eye Disease Study-2; (3) use of enhanced-depth imaging optical coherence tomography for choroidal imaging; (4) use of gene therapy to treat choroideremia; (5) use of combination pharmacotherapy (i.e., squalamine + ranibizumab) and gene therapy to treat the neovascular complications of AMD; and (6) use of stem cell-derived retinal pigment epithelium transplants to treat atrophic AMD and Stargardt macular dystrophy. In addition, we review the ocular and systemic risks associated with sustained intraocular steroid delivery and inhibition of vascular endothelial growth factor signaling pathways. We also review potential applications of gene- versus cell-based therapy for the treatment of retinal degenerative diseases. Conclusions Several treatment approaches are effective in the treatment of diabetic macular edema. Prophylaxis against AMD progression with Age-Related Eye Disease Study-2 supplements seems to reduce the risk of developing neovascular but not atrophic complications of AMD. Enhanced-depth imaging optical coherence tomography data provide new information on the role of the choroid in a variety of conditions. Advances in gene- and cell-based therapy will revolutionize the development of regenerative medicine in ophthalmology.

Journals constitute an essential component of our information dissemination infrastructure because unlike meetings, the information contained therein is, or ought to be, subject to the rigors of peer review. I suspect that most of us rely heavily on the fidelity of the peer-review process to help create the zeitgeist of the scientific milieu in which we function. Unfortunately, even highly cited basic science research does not always produce results that are replicated.1,2 Errors in study design seem to occur more frequently than they should, even in basic research.3 Constructive, critical peer review is thus an essential part of our information dissemination process. We are indebted to the TVST reviewers for the immensely important contributions they have made to the quality of the journal and for the service they have provided to the entire vision research community. On behalf of our Associate Editors, Editors, and readers, I thank each of you sincerely. Among the highly accomplished individuals who have generously donated their time and expertise for our benefit, a subset have made outstanding contributions due to the exceptional care with which they have reviewed manuscripts. The Editors of TVST have been asked to recognize these individuals by identifying them as “exceptional reviewers.” I am pleased to offer special recognition to these individuals as part of our thanks to each of the reviewers for TVST. TVST is our journal, and it will be as useful a source of information as we make it through the submission of our work and, no less, through the peer review to which that work is subjected. Thank you again for your important contribution as an “exceptional reviewer”!

PURPOSE To describe the demographics, characteristics, management, and visual outcomes of eyes diagnosed with endophthalmitis after open globe injury. METHODS Retrospective cohort analysis of all patients diagnosed with endophthalmitis after open globe injury from 1997 to 2015 at University Hospital, Newark, NJ. RESULTS Twenty-six eyes were identified (all male patients; mean age: 37 ± 15 years). Cultures were positive in 16 eyes (62%), with Staphylococcus species (7 eyes, 44%) being the most common organism. Twelve eyes (46%) presented with open globe injury and concurrent endophthalmitis; 14 eyes (54%) developed endophthalmitis a mean of 14 days after open globe repair (OGR; 1 outlier of 98 days excluded). All eyes were managed with systemic and intravitreal antibiotics. The presence of intraocular foreign body (P < 0.05) and delayed primary OGR (P < 0.03) were significantly more common with concurrent versus post-OGR endophthalmitis. Four (29%) eyes in the post-OGR endophthalmitis group had corneal wound leak after OGR. Four (15%) eyes with no light perception vision were enucleated. Ten (40%) of 25 eyes with documented best-corrected visual acuity had final best-corrected visual acuity ≥20/200; final best-corrected visual acuity ranged from no light perception to 20/20. CONCLUSION The presence of intraocular foreign body and delayed presentation were significantly more common with concurrent endophthalmitis. Twenty-nine percent of eyes that presented with endophthalmitis after OGR had a wound leak. Final best-corrected visual acuity ≥20/200 was achieved in 40% of cases.

Protocol I, a multicenter randomized clinical trial, compared the visual outcomes of patients treated with 0.5 mg intravitreal ranibizumab with either prompt or deferred (by 24 weeks laser), 4 mg intravitreal triamcinolone with prompt laser, or sham injection with prompt laser for the treatment of center-involving diabetic macular edema (DME). A total of 854 adult patients with type I or II diabetes and any level of non-proliferative diabetic retinopathy or proliferative retinopathy with adequate panretinal photocoagulation, with best-corrected visual acuity (BCVA) of 78 to 24 ETDRS letters (Snellen equivalent of 20/32 to 20/320) and visual loss attributed to macular edema, or retinal thickening with central subfield thickness of at least 250 µm by OCT were enrolled. The main outcomes relevant for practicing clinicians are as follows. (1) Intravitreal ranibizumab treatment provides superior visual outcomes compared to conventional laser treatment. (2) Adjunctive laser treatment does not appear to provide substantial visual benefit compared to ranibizumab treatment alone, but may reduce the number of injections required to resolve DME. Deferral of laser is likely beneficial in patients with worse initial visual acuity. (3) Intravitreal triamcinolone provides similar visual outcomes compared to intravitreal ranibizumab in pseudophakic patients but is associated with a clinically important increased risk of increased intraocular pressure (IOP), need for glaucoma medications, and need for glaucoma surgery. (4) Delayed initiation of intravitreal ranibizumab therapy provides improved visual outcome among patients initially treated with conventional laser photocoagulation or triamcinolone, but the magnitude of the benefit is not as great as is observed when ranibizumab treatment is initiated promptly. (5) The number of ranibizumab injections required to achieve the desired visual outcome decreases substantially after the first year, with the majority of patients not requiring further treatment after 3 years. (6) Patients who do not have a rapid response to ranibizumab still display long-term benefit to continued therapy, although perhaps less than those with immediate improvement. (7) Intravitreal ranibizumab is not only effective in reducing retinal edema and improving BCVA among patients with DME, it is also a disease modifying therapy and induces improvement of the diabetic retinopathy severity score by 2 or more steps in approximately one third of patients. Triamcinolone injection also induces improvement in diabetic retinopathy severity in DME patients, but perhaps to a lesser degree. (8) No increased risk of systemic adverse events was observed among patients treated with intravitreal ranibizumab compared to sham-injected controls or triamcinolone-treated patients, but the low frequency of adverse events, restrictive enrollment criteria, and specific posology employed in this study limit the generalization of this conclusion to patients routinely encountered in clinical practice. (9) There was no clinically important increased risk of major ocular complications among patients treated with intravitreal ranibizumab (including the risk of glaucoma), although endophthalmitis is a potentially devastating outcome should it occur. In addition to the risk of endophthalmitis, intravitreal triamcinolone injection was associated with clinically important increased risk of cataract progression and increased IOP.

Two critical questions one must answer as one applies the results of a clinical trial to clinical practice are: (1) Regardless of whether the trial result is likely to be replicated or reproduced in a second large-scale trial, are the results likely to be reproduced in one's practice? (2) Regardless of whether the experimental treatment was better than the alternative on average for a population of patients, are the results clinically important for a given patient in one's practice? To determine if a study result is likely to be reproduced in one's clinical practice, it may be helpful to answer 5 questions: (1) Have steps been taken to minimize bias? (2) Is the result likely due to the treatment? (3) Is the result unlikely due to chance? (4) Is the study population representative of one's patients? (5) Is the totality of evidence consistent? If the answer to all 5 questions is "yes," then we posit that the trial result is likely to be reproduced in one's practice. If not, the likelihood of reproducibility is low. If the answer is yes to all questions except the last, then reproducibility in one's practice is not clear and depends on the strength of the prior versus the current evidence. If the prior evidence is strong, such as multiple pivotal randomized clinical trials, and if the current trial result is not consistent with the previous studies, then the current result may not be reproduced in one's practice. To determine if a study result is clinically important, a 3-step approach is suggested. Step 1. Decide, a priori, what a clinically meaningful difference between 2 treatments would be. This choice defines regions of beneficial, harmful, and trivial outcomes. Step 2. Identify the confidence intervals (CIs). Determine whether the 95% CI mostly includes the range of clinically beneficial outcomes and lies outside the range of clinically harmful outcomes. If these conditions are met, the result is probably clinically important, but the result may or may not be statistically significant. Put the CIs and the regions of benefit/harm together to make a decision about clinically important effects. Step 3. Assess the proportion of eyes with clinically meaningful changes in vision. The proportion of "responders" among patients receiving a given treatment reflects the likelihood of one's patient having a clinically meaningful response to the treatment. In summary, not all statistically significant results are reproduced, even those of carefully designed clinical trials. Determining if a study result is likely to be reproduced in one's practice is even more problematic. The 5-question test may help in this regard. The 5-question test attempts to assess whether steps have been taken to: minimize bias; avoid confounding; ensure adequate statistical power to support precision in the estimates of population parameters; insure external validity of the trial result; and determine whether there is a convergence of evidence consistent with the trial's major findings. To determine if a statistically significant result is likely to be clinically important, a 3-step approach may be useful, focusing on CIs and the proportion of eyes with clinically meaningful changes in vision. Application of clinical trial results to clinical practice requires critical analysis of the extant literature and good clinical judgment.

For decades, panretinal photocoagulation (PRP) has been the standard of care for the treatment of proliferative diabetic retinopathy (PDR). The relatively recent advent of anti-vascular endothelial growth factor (VEGF) formulations for intravitreal injection has provided a fresh perspective on PDR treatment, especially in eyes with concurrent diabetic macular edema (DME). The anti-VEGF agent ranibizumab has demonstrated a potentially protective effect on eyes with DME in terms of progression to PDR in the RIDE/RISE trials, as has aflibercept in the VIVID/VISTA trials. In 2015, these 2 agents were approved by the Food and Drug Administration for the treatment of PDR with DME, though PRP still remains the standard of care for eyes without baseline DME. Published results from Protocol S illustrate the non-inferiority of ranibizumab versus PRP in the treatment of PDR, the first prospective study to do so in eyes with and without baseline DME. These results also reveal that treatment with ranibizumab, when compared to standard treatment with PRP, may also lead to less peripheral visual field loss, reduced need for vitrectomy, and reduced chance for developing DME. Both PRP and intravitreal ranibizumab have very low rates of adverse events. However, treatment with anti-VEGF agents generally is associated with higher costs, increased need for follow-up, and the risk of potentially catastrophic ocular complications (e.g., endophthalmitis) and systemic side effects. Anti-VEGF agents should be considered in cases of media opacity preventing completion of PRP in compliant patients without recent cerebrovascular accident or myocardial infarction, though the long-term efficacy of these agents remains to be studied, especially after the discontinuation of injections.

Importance Patients with diabetic macular edema (DME) are at high risk of vascular complications, including stroke and myocardial infarction (MI). Concerns have been raised that intravitreal dosing of vascular endothelial growth factor inhibitors in DME could be associated with an increase in cardiovascular and cerebrovascular adverse events. Objective To evaluate the cardiovascular and cerebrovascular safety of ranibizumab, 0.5 mg and 0.3 mg, compared with sham with and without laser in DME. Data Sources Patient-level data from 6 randomized, double-masked, sham- and laser-controlled clinical trials. Study Selection Company-sponsored (Genentech or Novartis) studies in DME completed as of December 31, 2013. Data Extraction and Synthesis Pairwise comparisons (ranibizumab, 0.5 mg, vs sham and laser; ranibizumab, 0.3 mg, vs sham) were performed using Cox proportional hazard regression (hazard ratios, 95% CIs) and rates per 100 person-years. Data analysis was conducted from June 1 to July 15, 2015. Main Outcomes and Measures Standardized Medical Dictionary for Regulatory Activities queries and extended searches were prospectively defined to identify relevant safety end points, including arterial thromboembolic events, MI, stroke or transient ischemic attack, vascular deaths, and major vascular events as defined by the Antiplatelet Trialists’ Collaboration (APTC). Results Overall, 936 patients were treated with ranibizumab, 0.5 mg; 250 patients with ranibizumab, 0.3 mg; and 581 patients with sham/laser. The hazard ratios associated with all pairwise comparisons included 1 for all key cardiovascular and cerebrovascular safety end points. For ranibizumab, 0.5 mg, vs sham/laser and ranibizumab, 0.3 mg, vs sham, the hazard ratios were, respectively, arterial thromboembolic events, 1.05 (95% CI, 0.66-1.68) and 0.78 (95% CI, 0.43-1.40); MI, 0.84 (95% CI, 0.41-1.72) and 0.94 (95% CI, 0.43-2.06); stroke or transient ischemic attack, 0.94 (95% CI, 0.44-1.99) and 0.53 (95% CI, 0.19-1.42); stroke (excluding transient ischemic attack), 1.63 (95% CI, 0.65-4.07) and 0.59 (95% CI, 0.14-2.46); vascular death, 2.17 (95% CI, 0.57-8.29) and 2.51 (95% CI, 0.49-12.94); and APTC-defined events, 1.09 (95% CI, 0.63-1.88) and 1.00 (95% CI, 0.51-1.96). Conclusions and Relevance This pooled analysis includes 1 of the largest patient-level data sets on treatment of DME with ranibizumab. Although still underpowered to detect small differences for infrequent events, such as stroke, the findings suggest that intravitreous ranibizumab does not increase the risk of systemic vascular events. However, uncertainty remains for patients with DME who are at high risk for vascular disease and were not included in these trials.

Purpose: To review the results of Diabetic Retinopathy Clinical Research Network Protocol T, as applied to clinical practice. Methods: Review of major publications reporting the results of Protocol T, a randomized single-masked (in year-1 only), multicenter clinical trial comparing aflibercept, bevacizumab, and ranibizumab as treatment option for center-involving diabetic macular edema (DME). The main outcome measures were change in visual acuity (VA), central subfield thickness (CST) on optical coherence tomography, cost effectiveness, burden of care, and safety. Results: A total of 660 participants (mean age 61 ± 10 years, 47% women, 65% Caucasian) were randomized to treatment with aflibercept (n = 224), ranibizumab (n = 218), or bevacizumab (n = 218). The majority of patients (90%) had type II diabetes, with an average duration of 17 ± 11 years. About half the patients had baseline ETDRS VA of 20/32 to 20/40, and half had ETDRS VA of 20/50 to 20/320 in all 3 cohorts. Patients in all 3 cohorts received a similar number of injections during the study period (9-10 in year-1; 5-6 in year-2). The year-1 improvement in ETDRS letters was significantly higher for aflibercept than for ranibizumab and bevacizumab in patients with baseline VA 20/50 or worse (p = 0.003 and p 0.74). Bevacizumab was less effective than the other agents in decreasing CST at years-1 and -2 in the overall cohort of patients (p < 0.001). However, bevacizumab is substantially cheaper and much more cost-effective (when comparing expense and quality of life measures) than aflibercept and ranibizumab. The cost of other agents would have to decrease by 80-90% to be cost-effective relative to bevacizumab. Intravitreal administration of anti-VEGF therapy has relatively few ocular and systemic side effects, but caution may be warranted for patients with a recent history or high risk of myocardial infarction or stroke. Conclusions: Aflibercept, bevacizumab, and ranibizumab are highly effective treatments for DME. Bevacizumab is more cost-effective than aflibercept and ranibizumab. Intravitreal administration of drugs is relatively safe; however, intravitreal administration may be associated with severe systemic side effects in a small percentage of patients, particularly in those with a prior history of or high risk of Anti-Platelet Trialists' Collaboration events.

For decades, panretinal photocoagulation (PRP) has been the standard of care for the treatment of proliferative diabetic retinopathy (PDR). The relatively recent advent of anti-vascular endothelial growth factor (VEGF) formulations for intravitreal injection has provided a fresh perspective on PDR treatment, especially in eyes with concurrent diabetic macular edema (DME). The anti-VEGF agent ranibizumab has demonstrated a potentially protective effect on eyes with DME in terms of progression to PDR in the RIDE/RISE trials, as has aflibercept in the VIVID/VISTA trials. In 2015, these 2 agents were approved by the Food and Drug Administration for the treatment of PDR with DME, though PRP still remains the standard of care for eyes without baseline DME. Published results from Protocol S illustrate the non-inferiority of ranibizumab versus PRP in the treatment of PDR, the first prospective study to do so in eyes with and without baseline DME. These results also reveal that treatment with ranibizumab, when compared to standard treatment with PRP, may also lead to less peripheral visual field loss, reduced need for vitrectomy, and reduced chance for developing DME. Both PRP and intravitreal ranibizumab have very low rates of adverse events. However, treatment with anti-VEGF agents generally is associated with higher costs, increased need for follow-up, and the risk of potentially catastrophic ocular complications (e.g., endophthalmitis) and systemic side effects. Anti-VEGF agents should be considered in cases of media opacity preventing completion of PRP in compliant patients without recent cerebrovascular accident or myocardial infarction, though the long-term efficacy of these agents remains to be studied, especially after the discontinuation of injections.

Two critical questions one must answer as one applies the results of a clinical trial to clinical practice are: (1) Regardless of whether the trial result is likely to be replicated or reproduced in a second large-scale trial, are the results likely to be reproduced in one's practice? (2) Regardless of whether the experimental treatment was better than the alternative on average for a population of patients, are the results clinically important for a given patient in one's practice? To determine if a study result is likely to be reproduced in one's clinical practice, it may be helpful to answer 5 questions: (1) Have steps been taken to minimize bias? (2) Is the result likely due to the treatment? (3) Is the result unlikely due to chance? (4) Is the study population representative of one's patients? (5) Is the totality of evidence consistent? If the answer to all 5 questions is "yes," then we posit that the trial result is likely to be reproduced in one's practice. If not, the likelihood of reproducibility is low. If the answer is yes to all questions except the last, then reproducibility in one's practice is not clear and depends on the strength of the prior versus the current evidence. If the prior evidence is strong, such as multiple pivotal randomized clinical trials, and if the current trial result is not consistent with the previous studies, then the current result may not be reproduced in one's practice. To determine if a study result is clinically important, a 3-step approach is suggested. Step 1. Decide, a priori, what a clinically meaningful difference between 2 treatments would be. This choice defines regions of beneficial, harmful, and trivial outcomes. Step 2. Identify the confidence intervals (CIs). Determine whether the 95% CI mostly includes the range of clinically beneficial outcomes and lies outside the range of clinically harmful outcomes. If these conditions are met, the result is probably clinically important, but the result may or may not be statistically significant. Put the CIs and the regions of benefit/harm together to make a decision about clinically important effects. Step 3. Assess the proportion of eyes with clinically meaningful changes in vision. The proportion of "responders" among patients receiving a given treatment reflects the likelihood of one's patient having a clinically meaningful response to the treatment. In summary, not all statistically significant results are reproduced, even those of carefully designed clinical trials. Determining if a study result is likely to be reproduced in one's practice is even more problematic. The 5-question test may help in this regard. The 5-question test attempts to assess whether steps have been taken to: minimize bias; avoid confounding; ensure adequate statistical power to support precision in the estimates of population parameters; insure external validity of the trial result; and determine whether there is a convergence of evidence consistent with the trial's major findings. To determine if a statistically significant result is likely to be clinically important, a 3-step approach may be useful, focusing on CIs and the proportion of eyes with clinically meaningful changes in vision. Application of clinical trial results to clinical practice requires critical analysis of the extant literature and good clinical judgment.

Trophic factors are endogenously secreted proteins that act in an autocrine and/or paracrine fashion to affect vital cellular processes such as proliferation, differentiation, and regeneration, thereby maintaining overall cell homeostasis. In the eye, the major contributors of these molecules are the retinal pigment epithelial (RPE) and Müller cells. The primary paracrine targets of these secreted proteins include the photoreceptors and choriocapillaris. Retinal degenerative diseases such as age-related macular degeneration and retinitis pigmentosa are characterized by aberrant function and/or eventual death of RPE cells, photoreceptors, choriocapillaris, and other retinal cells. We discuss results of in vitro and in vivo animal studies in which candidate trophic factors, either singly or in combination, were used in an attempt to ameliorate photoreceptor and/or retinal degeneration. We also examine current trophic factor therapies as they relate to the treatment of retinal degenerative diseases in clinical studies.

PURPOSE:: To describe the characteristics of nail gun-related open-globe injuries. METHODS:: Retrospective series of all patients presenting with open globes secondary to nail gun injury from 2000 to 2010. Data were collected on demographics, setting of accident, presenting clinical examination findings, visual acuity, management, surgical procedures needed, and long-term outcomes. RESULTS:: Forty-two patients (43 eyes; mean age, 31.6 years; 100% male; 79% Hispanic) suffered open-globe injury from nail gun accidents. Thirty-seven eyes (86%) sustained injury at work. One of 15 (6.7%) patients, on whom data were available, wore protective eyewear during the incident. Entrance wounds were classified into Zone I (n = 24 [56%]), Zone II (n = 12 [28%]), and Zone III (n = 7 [16%]). Six eyes (14%) had retained intraocular foreign bodies. Mean presenting logarithm of the minimum angle of resolution visual acuity was 1.64 ± 0.83, whereas mean final logarithm of the minimum angle of resolution visual acuity was 1.01 ± 0.96 (P = 0.004). Two eyes (4.7%) had no light perception vision at final examination. Seventeen (40%) patients developed a traumatic cataract, and 2 (4.7%) had dislocated lens fragments. Most common findings on presentation included vitreous hemorrhage (n = 30 [70%]) and hyphema (n = 28 [64%]). Two eyes (4.7%) had a retinal detachment at presentation, and 10 (23%) developed a retinal detachment during follow-up visits. Anatomical success was observed in 11 eyes (92%) with a retinal detachment. Three eyes (7.0%) became phthisical or prephthisical, and 1 was enucleated for severe pain. No eyes developed endophthalmitis or sympathetic ophthalmia. CONCLUSION:: This is the largest compilation of nail gun-related open-globe injury reported to date. Posterior segment complications, noted in the majority of cases, likely contributed to the overall guarded visual outcomes. Preventative measures for eye protection should be strictly followed while using nail guns. Language: en

Aims: To describe the demographics, characteristics and outcomes of open -globe injuries (OGI) with respect to zone of injury. Methods: Medical records of all patients presenting with OGIs to University Hospita l, Newark, NJ between January 2001 and December 2008 with a follow-up of at least 3 months were reviewed. Demographics, characteristics of the trauma and outcomes were compared with respect to the zone of injury; location of injury is confined to the corn ea and limbus in zone 1 (Z1), 5mm posterior to the limbus in zone 3 (Z3). Results:Of the 309 patients (310 eyes) identified, 228 (74%) were male. The mean age at presentationwas 35.3years (1-96). Meanfollow-up was 22.8 months (3-108 months). Most of the eyes presented with Z1 injury: 141 eyes (46%) Z1 injury, 83 (27%)Z2 and 86 (28%) Z3. Rupture was the most common type of injury in Z2 and Z3 injuries. Nineteen (86%) of 22 eyes with an intraocular fore ign body(IOFB) had a Z1 injury. 32 (42%) of 77 eyes with Z3 injury had no light perception (NLP) at presentation, compared with 9 (8%) of 119 Z1 and 13 (17%) of 78 Z2 -injured eyes. Four percent of Z1, 11% of Z2 and 18% of Z3-injured eyes had a final visi

Herein, we discuss recent applications of nanotechnology to ophthalmology, including nanoparticles for drug, gene, and trophic factor delivery; regenerative medicine (in the areas of optogenetics and optic nerve regeneration); and diagnostics (eg, minimally invasive biometric monitoring). Specific applications for the management of choroidal neovascularization, retinal neovascularization, oxidative damage, optic nerve damage, and retinal degenerative disease are considered. Nanotechnology will play an important role in early- and late-stage interventions in the management of blinding diseases.

Retinal pigment epithelium (RPE) cells produce neurotrophic factors that rescue photoreceptors from degeneration. Previously, we showed that conditioned medium (CM) from fetal vs adult RPE cells resulted in significantly better porcine retinal preservation, and possessed significantly higher levels of hepatocyte growth factor (HGF) and pigment epithelium-derived factor (PEDF). This study aimed to further describe the effects of human fetal RPE-CM on porcine and aged human retina, and to characterize its effects biochemically. RPE-CM was harvested from passage-2 fetal RPE, 7 days after passage, 24-hours after exposure to basal medium. After culture in RPE-CM, porcine retinal morphology was assessed with confocal microscopy. The effects of RPE-CM on porcine and aged human retina survival were assessed by cytotoxicity and apoptosis biochemical assays. To characterize RPE-CM biochemically, effects of heating, digesting with proteinase-K, dilution, concentration, and fractionation were tested. Recombinant proteins and neutralizing antibodies were used to identify proteins that might contribute to the salutary effects of RPE-CM on porcine retina. Culturing porcine retina in RPE-CM significantly preserved outer nuclear layer width and the number of nuclei in cross-section, and significantly decreased photoreceptor axon retraction. RPE-CM decreased porcine retinal death by 17–34 % (p

To evaluate characteristics and prognostic factors for functional success in eyes that present with no light perception (NLP) after open globe trauma.The medical records of all subjects presenting to a single university referral center with visual acuity (VA) of NLP after sustaining an open globe eye injury from January 1, 2001, through June 30, 2010, were retrospectively analyzed to determine epidemiologic and clinical factors associated with visual outcomes.Of the 73 NLP eyes (73 patients) that underwent primary repair and were included in the study, final VA was 20/100 in 1 eye (1%), counting fingers in 2 eyes (3%), hand motion in 9 eyes (12%), light perception in 5 eyes (7%), and NLP in 56 eyes (77%). Recovery of some vision on postoperative Day 1, pars plana vitrectomy operation, and Zone 2 injury were significantly associated with an improvement in final VA. Zone 3 injuries were the most likely to result in NLP final VA, although this difference was not statistically significant.Visual recovery to light perception or better on postoperative Day 1 increases the likelihood of having a long-term improvement in VA. Pars plana vitrectomy may be beneficial in such eyes if posterior segment abnormalities are noted.

The earliest impact of nanomedicine in ophthalmology is likely to involve the areas of biopharmaceuticals, implantable materials (e.g. tissue regeneration scaffolds, bioresorbable materials), implantable devices (e.g. glaucoma drainage valves), and diagnostic tools (e.g. intraocular pressure (IOP) monitors). Nanotechnology will bring about the development of regenerative medicine (i.e. replacement and improvement of cells, tissues, and organs) and artificial vision. In this chapter, we review ophthalmic applications of nanotechnology in the following areas: drug and trophic factor therapy for glaucoma, retinal degenerative, and retinal vascular disease; gene therapy for retinal degenerative disease; regenerative medicine, including optogenetics and optic nerve regeneration; and diagnostics (minimally invasive IOP monitoring). Nanotechnology will play an important role in both early-stage and late-stage intervention in the management of blinding diseases.

Aims: To characterize gender differences in the ophthalmic findings and clinical outcomes of patients with open globe (OG) injuries. Study Design: Retrospective case series. Place and Duration of Study: Department of Ophthalmology, University Hospital, New Jersey Medical School between January 2001 and June 2010. Methodology: The medical records of all patients presenting with OG injuries to University Hospital, Newark, NJ from January 1, 2001 through June 30, 2010 were reviewed. Demographics, characteristics of the trauma, ophthalmic findings, and outcomes were compared in male and female patients. Results: A total 603 eyes (602 patients) with OG injuries were identified. Most of the patients (76.4%) were male. The mean patient age was 39.14 years which was significantly lower in males (35.66 years vs. 50.43 years in females; p

Transplanted cells can secrete numerous molecules that may exert a beneficial effect on the host retina and/or choroid even if they do not cure the underlying disease. Ideally, with a single transplant operation, many different pathways can be modified, which may reduce the chance of ‘escape’ associated with typical pharmacotherapy as well as the need for repeated drug administration. In addition, transplanted cells can replace dead cells (e.g. photoreceptors). Because of their pluripotency and unlimited proliferative capacity, stem cells seem to be a logical choice for starting material because they can be produced en masse safely and they can be induced to differentiate into ocular cells with potential for replacement and rescue therapy. Although preclinical studies demonstrate the feasibility of using embryonic stem cells and induced pluripotent stem cells for treating degenerative retinal diseases associated with abnormalities in the retinal pigment epithelium and/or photoreceptors, some issues may limit the use of stem cells in clinical practice. These issues include: immunogenicity of the cells, stability of cell phenotype (both inherent and environment-induced), the propensity to form tumors in situ, the abnormal microenvironment that can accompany degenerative disease and the synaptic rewiring that accompanies retinal degeneration. In the case of non-exudative age-related macular degeneration, cell transplants might prevent progression of geographic atrophy (through replacement of dysfunctional or dead RPE) and might even bring about some visual improvement in selected cases (through rescue of photoreceptors that are dying but not dead). Cell-based therapy may one day be sight-restoring for patients who are blind due to retinal degeneration of various etiologies. RPE transplantation is an attractive starting point for this sort of therapy as these cells can integrate with the host retina easily.

Purpose To describe the demographics, characteristics, management, and outcomes of eyes with endophthalmitis related to infectious keratitis. Methods Retrospective chart review of all patients treated for infectious keratitis-associated infectious endophthalmitis between 2001 and 2014 at University Hospital, Rutgers New Jersey Medical School. Results Thirty-eight cases with infectious keratitis-associated infectious endophthalmitis were identified (21 men [55%], mean age: 66.2 ± 20.7 years), with average time from the beginning of ulcer symptoms to endophthalmitis of 11.0 days. Associated systemic conditions (diabetes, HIV, immunosuppressive therapy, cirrhosis, or dementia) were present in 57.9%; 60.5% had previous intraocular surgery. Etiology showed gram-positive bacteria in 14 cases (36.9%), gram-negative bacteria in 7 (18.4%), fungi in 4 (10.5%), and no growth/unknown in 12 (31.6%). Nineteen cases (50%) presented with no light perception and were primarily enucleated. The remaining 19 eyes each received intravitreal antibiotics (mean: 1.5 injections); 8 (42.0%) underwent pars plans vitrectomy with vitreous biopsy, whereas 5 (26.3%) received emergency corneal transplantation. Final visual acuity was no light perception in 6 eyes (3 secondarily enucleated), light perception in 2, hand motion in 7, counting fingers in 2, and ≥20/50 in 2. Conclusion Our study of 38 eyes with infectious keratitis-associated infectious endophthalmitis revealed generally poor visual outcomes and a high rate of systemic conditions and previous intraocular surgery.

Purpose To describe the characteristics, demographics, anatomic and functional outcomes, and complications of diabetic eyes with traction retinal detachment (TRD) or combined traction/rhegmatogenous retinal detachment that underwent pars plana vitrectomy (PPV) silicone oil (SO) tamponade. Methods In this retrospective chart review, exclusion criteria included previous PPV. Results Forty eyes were identified. The mean preoperative complexity score (CS) of the TRDs was 5.95 (range 4-8). In patients with ≥6 months of follow-up (33; 82.5%), eyes with lower CSs had a better mean final visual acuity (VA): ~20/400 for CS 4, and hand motions (HM)-1/200 for CS >5. Eyes with macula-sparing TRDs had better final VA (~20/400) than those with a detached macula (~HM). Eyes with >3 panretinal photocoagulation sessions attained better mean final VA (20/400) than eyes without any history of laser treatment (~HM). The most frequent complications were cataract (46%), preretinal fibrosis (33%), recurrent TRD (15%), oil migration to the anterior chamber (12%), corneal edema (12%), and oil emulsification (9%). Eleven (27.5%) eyes underwent SO removal. Conclusions The average complexity score was high in this series. Use of SO tamponade for diabetic TRDs is not without complications, but may be beneficial in stabilizing vision in eyes with otherwise poor prognosis.