POSTCATARACT ENDOPHTHALMITIS TREATED WITH SMALL GAUGE VITRECTOMY.

PURPOSE: To discuss the use of minimally invasive, small gauge vitrectomy for acute postcataract endophthalmitis in patients with better than light-perception vision. PATIENT: 71-year-old man presented with redness, pain, and decreased vision of his left eye 11 days after cataract extraction. His visual acuity was counting fingers at 1 foot and slit-lamp examination revealed severe conjunctival injection, corneal edema, and hypopyon. The clinical impression was of acute postcataract endophthalmitis. METHODS: Patient was taken for immediate vitrectomy with simultaneous vitreous tap for culture, PCR, and injection of intravitreal vancomycin and ceftazidime. RESULTS: Culture and PCR of vitreous sample were positive for Staphylococcus epidermidis. Vision improved to 20/20 1 month postoperatively with complete resolution of vitreous inflammation and retinal vasculitis. CONCLUSION: In postcataract endophthalmitis with dense vitritis and diffuse retinal vasculitis, immediate, 25-gauge vitrectomy may result in return of baseline visual acuity.

TISSUE PLASMINOGEN ACTIVATOR FOR SUBFOVEAL HEMORRHAGE DUE TO AGE-RELATED MACULAR DEGENERATION: Comparison of 3 Treatment Modalities.

PURPOSE: To analyze and compare the effects of three common treatment modalities for a thick subfoveal hemorrhage due to exudative age-related macular degeneration on final visual acuity and the size of the final subretinal scar. DESIGN: Retrospective case series. SETTING: Single-site, tertiary referral center. PATIENTS: Thirty-nine patients with exudative age-related macular degeneration and acute SMH greater than 250 µm. INTERVENTION: Patients received vitrectomy with a subretinal tissue plasminogen activator (tPA) injection, pneumatic displacement (PD) with intravitreal tPA, or PD without tPA within 2 weeks of presentation. MAIN OUTCOME MEASURE: Functional outcome was determined by Snellen visual acuity. Anatomical outcome was determined as the final disciform scar size. RESULTS: Treatment groups did not differ in age, sex, initial visual acuity, the initial area of the thick subfoveal hemorrhage, follow-up duration, lens status, duration of exudative age-related macular degeneration, previous intravitreal bevacizumab injections, or time from last given injection to the acute thick subfoveal hemorrhage. Final visual acuity improved significantly in both the vitrectomy and subretinal tPA injection group (P < 0.001), and the intravitreal tPA injection group (P = 0.002) but not with PD alone. Patients treated with subretinal tPA achieved 40% ± 54% reduction in final scar area, in contrast to 27% ± 35% decrease in patients treated with intravitreal tPA (P = 0.001). CONCLUSION: Treatment with tPA improves the functional and anatomical outcomes in patients with thick subfoveal hemorrhage due to subfoveal choroidal neovascular membrane secondary to exudative age-related macular degeneration and was superior to PD without tPA. Vitrectomy with subretinal tPA injection reduced the final disciform scar compared with PD with or without intravitreal tPA.

A Comparison of Immediate and Delayed Vitrectomy for the Management of Vitreous Hemorrhage due to Proliferative Diabetic Retinopathy.

BACKGROUND AND OBJECTIVE: To compare immediate and delayed vitrectomy for the management of vitreous hemorrhage (VH) due to proliferative diabetic retinopathy (PDR). PATIENTS AND METHODS: Retrospective review of 134 eyes receiving vitrectomy for non-clearing, PDR-associated VH. Primary outcome was area under the vision curve (AUC) in patients receiving immediate (< 30 days) versus delayed (> 30 days) vitrectomy with endolaser. RESULTS: Forty-six eyes were included, with 17 undergoing immediate (< 30 days) vitrectomy with endolaser and 29 undergoing delayed (> 30 days) vitrectomy with endolaser. Time to vitrectomy was 14.8 days ± 8.26 days compared to 629.6 days ± 894.9 days in the immediate and delayed groups, respectively. AUC was significantly greater for patients undergoing delayed versus immediate vitrectomy (276.1 ± 0.601 logMAR*time versus 165.7 ± 0.761 logMAR*time; P < .0001). There was no difference in AUC postoperatively for delayed versus immediate surgery. Both groups required significantly less postoperative panretinal photocoagulation (P < .05). Preoperative and final visual acuities were equivalent (immediate: 1.86 ± 0.99 and 0.35 ± 0.25; P = .002; delayed: 1.71 ± 1.05 and 0.31 ± 0.34; P < .0001). CONCLUSIONS: Immediate vitrectomy with endolaser for PDR-associated VH (< 30 days) decreases time spent with vision loss and the need for adjunctive PRP. Modern vitrectomy is safe and may be considered earlier in VH management.

Deletion of endoplasmic reticulum stress-induced CHOP protects microvasculature post-spinal cord injury.

Trauma introduces damaging stressors that compromise protein, lipid, and nucleic acid integrity. Aggregates of unfolded and misfolded proteins in the endoplasmic reticulum (ER) triggers the ER stress response (ERSR)/unfolded protein response (UPR) leading to activation of three signaling pathways mediated by PERK, ATF6, and IRE1. Initially, the ERSR/UPR is pro-homeostatic as it globally slows translation while increasing translation of chaperone proteins and inducing ER-associated degradation. If the cellular stress is not controlled, apoptosis is subsequently induced through several mechanisms, of which the most well-described is CHOP. Following spinal cord injury (SCI), mice deficient in CHOP signaling show increased spared white matter and enhanced locomotor recovery by 6 weeks. At 24 hours after SCI, ATF4 and CHOP are upregulated in under perfused microvessels. We observed vascular protection 3 days post-SCI and a significant decrease in macrophage infiltration by the end of the first week. These results suggest that modulating ER-stress signaling in endothelial cells and macrophages may protect against vascular injury and attenuate inflammation post-SCI.

Targeting microvasculature for neuroprotection after SCI.

Spinal cord injury (SCI) is characterized by secondary degeneration, which leads to tissue loss at the epicenter and subsequent functional deficits. This review provides insight into the pathophysiology of microvascular dysfunction and endothelial cell loss, which are among the earliest responses during the first postinjury day. The enigmatic role of the angiogenic response in the penumbra around the lost tissue, which occurs during the first 2 weeks, is also discussed. The importance of stabilizing and rescuing the injured vasculature is now well-recognized, and several pharmacological and genetic treatments have emerged in the past few years. We conclude with suggestions for future experimental research, including development of vascular-selective treatments and exploitation of genetic models. In summary, vascular dysfunction following SCI is an important contributor to neurological deficits, as proposed long ago. However, there now appears to be new and potentially powerful opportunities for treating acute SCI by targeting the vascular responses.

Activating Notch signaling post-SCI modulates angiogenesis in penumbral vascular beds but does not improve hindlimb locomotor recovery.

Manipulation of Notch signaling has led to significant tumor shrinkage as well as recovery from several traumatic and ischemic injury models indicating its potential clinical application. We have tested both an agonist and antagonist of Notch signaling to study the effects of Notch-mediated angiogenesis on spinal cord vascular pathology following traumatic injury. Initial neonatal retinal vascularization assays showed their respective bioactivities in vivo. Mice were treated with either the antagonist Jagged1-Fc chimera (Jag1-Fc) or agonist Notch1 antibody (N1 Ab) immediately following a mid-thoracic contusive injury through an initial jugular bolus and tail vein injections for 3 days post-injury. After 14 days, activating Notch signaling decreased the overall vascular density within the penumbral gray matter compared to controls while maintaining the density of perfused vessels. Inhibiting Notch signaling did not change the density or perfusion of microvessels within the lesion penumbra. Furthermore, neither activation nor inhibition of Notch signaling significantly altered inflammation, hypoxia, and lesion volume in the epicenter and penumbra. Importantly, neither treatment changed locomotor function. In postnatal retinal vascular assays, administration of Jag1-Fc and N1 Ab increased and decreased both tip cell numbers and branch points in each treatment, respectively. However, these agents did not modulate primary CNS EC proliferation in vitro in spite of sufficient Notch ligand expression. We conclude that Notch signaling, while an important part of developmental angiogenesis, may play a lesser role in mediating vascular recovery following traumatic injury to the CNS.