Critical Role of CD55 in Controlling Wound Healing.

How reparative processes are coordinated following injury is incompletely understood. In recent studies, we showed that autocrine C3a and C5a receptor (C3ar1 and C5ar1) G protein-coupled receptor signaling plays an obligate role in vascular endothelial growth factor receptor 2 growth signaling in vascular endothelial cells. We documented the same interconnection for platelet-derived growth factor receptor growth signaling in smooth muscle cells, epidermal growth factor receptor growth signaling in epidermal cells, and fibroblast growth factor receptor signaling in fibroblasts, indicative of a generalized cell growth regulatory mechanism. In this study, we examined one physiological consequence of this signaling circuit. We found that disabling CD55 (also known as decay accelerating factor), which lifts restraint on autocrine C3ar1/C5ar1 signaling, concomitantly augments the growth of each cell type. The mechanism is heightened C3ar1/C5ar1 signaling resulting from the loss of CD55's restraint jointly potentiating growth factor production by each cell type. Examination of the effect of lifted CD55 restraint in four types of injury (burn, corneal denudation, ear lobe puncture, and reengraftment of autologous skin) showed that disabled CD55 function robustly accelerated healing in all cases, whereas disabled C3ar1/C5ar1 signaling universally retarded it. In wild-type mice with burns or injured corneas, applying a mouse anti-mouse CD55 blocking Ab (against CD55's active site) to wounds accelerated the healing rate by 40-70%. To our knowledge, these results provide new insights into mechanisms that underlie wound repair and open up a new tool for accelerating healing.

CASE REPORT OF THE ROLE OF OPTICAL COHERENCE TOMOGRAPHY IN RECOMBINANT GROWTH HORMONE THERAPY.

PURPOSE: To report the correlation between recombinant growth hormone (rhGH) dosage and retinal nerve fiber layer (RNFL) thickness values measured by optical coherence tomography in a case of pseudotumor cerebri syndrome (PTCS) after rhGH. METHODS: An 11-year-old girl was receiving rhGH for panhypopituitarism. The patient developed PTCS, and her rhGH dose was adjusted using optical coherence tomography RNFL thickness measurements. The linear correlation coefficient (r) and coefficient of determination (r2) were calculated to assess the relationship between RNFL thickness and rhGH dose. RESULTS: As the rhGH dosage was increased, the RNFL thickness values also increased, especially when acetazolamide was excluded because of its confounding effect. (r = 0.64) In separate subgroup analysis, a higher acetazolamide dosage strongly correlated with reduced RNFL thickness (r = 0.77). CONCLUSION: Although PTCS is a rare complication after rhGH therapy, its detrimental effects cannot be ignored. In our case report, we used optical coherence tomography RNFL values in addition to clinical findings to carefully titrate the rhGH dosage to prevent a flare-up of PTCS. Despite the obvious need for larger studies, our case report shows the value of RNFL thickness measured by optical coherence tomography and the valuable additional data it provides to refine rhGH therapy as an adjunct noninvasive method in PTCS.

The effects of bevacizumab treatment in a rat model of retinal ischemia and perfusion injury.

Purpose: To create a model of an ischemic retina with temporary ischemia and reperfusion (IR) and to examine the possible antiapoptotic and neurodegenerative effects of a vascular endothelial growth factor (VEGF) antagonist. Methods: Three groups were formed. Rats were subjected to continued ischemia for 45 min, and then reperfusion was allowed for 2 days. For the first group, ischemia was induced, but an anti-VEGF agent was not administered. For the second group, 2 days before ischemia, 0.005 ml (0.125 mg) of bevacizumab was administered intravitreally, and then the ischemic model was created. The last group's intraocular pressure was not increased as in the control group, and only a cannula was introduced into the anterior chamber through the cornea. Six animals from each group were subjected to histomorphometry, and four were subjected to immunohistochemical and histopathologic examinations. For a histomorphometric examination, the number of cells in the retinal ganglion cell (RGC) layer was counted using the optical dissector method. For immunohistochemistry, the vascular endothelial growth factor receptor-2 (VEGFR-2) levels and apoptosis were examined in the retinal and choroidal tissue. Results: It was observed that in an IR injury, bevacizumab reduces the death and apoptosis of cells in the RGC layer. It was also identified that although bevacizumab is a large molecule, the agent affects the choroid and reduces the amount of VEGFR-2 in this tissue. Conclusions: IR may be used as a model of ischemic retinopathy that includes VEGF-dependent vascular permeability and neurodegeneration. Although VEGF is a neurotrophic molecule, in IR injury, treatment with bevacizumab, which is an anti-VEGF agent, decreases apoptosis, showing that excess function of this molecule can be hazardous.

Bedside optical coherence tomography for Terson's syndrome screening in acute subarachnoid hemorrhage: a pilot study.

OBJECTIVE: Approximately 10% of patients with subarachnoid hemorrhage (SAH) become permanently, legally blind. The average cost of lifetime support and unpaid taxes for each blind person amounts to approximately $900,000. This study evaluates the feasibility and potential role of bedside optical coherence tomography (OCT) in Terson's syndrome (TS) in patients with acute SAH (aSAH) and its potential role in blindness prevention. METHODS: The authors conducted an open-label pilot study, in which 31 patients with an angiographic diagnosis of aSAH were first screened for TS with dilated funduscopy and then with OCT in the acute phase and at 6-week followup visits. Outpatient mood assessments (Patient Health Questionnaire­depression module, Hamilton Depression Scale), and quality of life general (NIH Patient-Reported Outcomes Measurement Information System) and visual scales (25-item National Eye Institute Visual Functioning Questionnaire) were measured at 1 and 6 weeks after discharge. Exclusion criteria included current or previous history of severe cataracts, severe diabetic retinopathy, severe macular degeneration, or glaucoma. RESULTS: OCT identified 7 patients with TS, i.e., a 22.6% incidence in our aSAH sample: 7 in the acute phase, including a large retinal detachment that was initially missed by funduscopy and diagnosed by OCT in follow-up clinic. Dilated retinal funduscopy significantly failed to detect TS in 4 (57.1%) of these 7 cases. Intraventricular hemorrhage was significantly more common in TS cases (85.7% vs 25%). None of the participants experienced any complications from OCT examinations. Neither decreased quality of life visual scale scores nor a depressed mood correlated with objective OCT pathological findings at the 6-week follow-up after discharge. There were no significant mood differences between TS cases and controls. CONCLUSIONS: OCT is the gold standard in retinal disease diagnosis. This pilot study shows that bedside OCT examination is feasible in aSAH. In this series, OCT was a safe procedure that enhanced TS detection by decreasing false-negative/inconclusive funduscopic examinations. It allows early diagnosis of macular holes and severe retinal detachments, which require acute surgical therapy to prevent legal blindness. In addition, OCT aids in ruling out potential false-positive visual deficits in individuals with a depressed mood at follow-up.

Horner Syndrome After Epidural Catheter Placement in a 4-Month-Old Child.

Although there are reports of iatrogenic Horner syndrome in the adult population, pediatric cases are rare. The current report presents a case of acquired Horner syndrome that occurred after an epidural catheter was placed for pain control. Horner syndrome completely resolved after removing the catheter and no imaging or further work-up was necessary. [J Pediatr Ophthalmol Strabismus. 2018;55:e1-e3.].

Prolonged Intracisternal Papaverine Toxicity: Index Case Description and Proposed Mechanism of Action.

BACKGROUND: Intracisternal papaverine (iPPV) is a vasodilator used for prophylaxis of intraoperative vasospasm during aneurysmal clipping. Postoperative side effects of iPPV include transient cranial nerve palsies, most commonly mydriasis owing to oculomotor nerve involvement, with rapid resolution. METHODS: We critically reviewed current literature on the adverse effects of iPPV in aneurysmal surgery with a focus on oculomotor nerve involvement. We also present the index case of prolonged bilateral mydriasis secondary to iPPV irrigation toxicity and its putative underlying mechanism. RESULTS: Papaverine toxicity occurs in the setting of its antimuscarinic action and blood-cerebrospinal fluid and blood-brain barrier compromise owing to acute subarachnoid hemorrhage and direct effect of papaverine. Our patient also experienced severe vasospasm and a minor stroke, both contributing to further blood-brain barrier disruption, and relatively acidic pH of the subarachnoid hemorrhage milieu. CONCLUSIONS: We propose that these factors perpetuate phase dynamics of papaverine crystals and facilitate a sustained slow release of papaverine within the cisternal system. Were it indicated, 0.3% iPPV would reasonably diminish the risk for neurotoxicity.

Cataract surgery in a patient with amyotrophic lateral sclerosis: a case report.

We report a cataract operation with complications in a patient with amyotrophic lateral sclerosis (ALS). The patient had a grade 4 mature brown cataract. Phacoemulsification with intraocular lens (IOL) implantation was planned; however, due to unexpected complications occurring during surgery, the operating technique was revised to an intracapsular cataract extraction. A very high vitreous pressure was found and therefore scleral fixating IOL was not implanted after anterior vitrectomy because of the possibility of choroidal effusion. The postoperative visual acuity improved sufficiently for the patient to communicate. Visual communication is of vital importance for an ALS patient and his caregivers. Therefore, surgery may be advisable in patients at a terminal stage with an advanced cataract, even if their general health condition may not seem appropriate for such an operation. Nevertheless, the intra- and postoperative course of the surgery may show unexpected complications and the surgeon should be prepared for such conditions.

Corneal biomechanical properties and intraocular pressure changes after phacoemulsification and intraocular lens implantation.

PURPOSE: To evaluate corneal viscoelastic and intraocular pressure (IOP) changes measured by an ocular response analyzer (ORA) after phacoemulsification and intraocular lens (IOL) implantation. SETTING: Yeditepe University Department of Ophthalmology, Istanbul, Turkey. METHODS: Fifty-one eyes scheduled for cataract surgery were included in the study. Corneal hysteresis (CH), corneal resistance factor (CRF), corneal-compensated intraocular pressure (IOPcc), and Goldmann-correlated IOP (IOPg) were measured by ORA preoperatively and 1 week and 1 and 3 months postoperatively. Central corneal thickness (CCT) was measured using the ORA's integrated handheld ultrasonic pachymeter. RESULTS: The mean preoperative CCT (537 microm+/-46 [SD]) did not change significantly by the end of 1 month postoperatively. The mean preoperative IOPcc (17.2+/-3.0 mm Hg) decreased significantly by 3 months postoperatively (15.2+/-3.7 mm Hg) (P= .018). The mean CH decreased from 10.36+/-1.48 mm Hg preoperatively to 9.64+/-1.26 mm Hg at 1 week (P= .028); it increased to preoperative values at the end of 1 month (10.20+/-1.70) and 3 months (10.74+/-1.54) (P>.05). The mean CRF decreased from 10.94+/-2.54 mm Hg preoperatively to 9.99+/-1.77 at 1 week (P= .026); it increased to preoperative values at 1 month (10.26+/-1.59) and 3 months (10.35+/-1.46) (P>.05). CONCLUSIONS: Although CH and the CRF decreased in the early postoperative period, the parameters increased and reached preoperative values by 3 months postoperatively, showing that corneal biomechanical properties are influenced by phacoemulsification and IOL implantation.