A Comparison of Trabeculectomy Surgery Outcomes With Mitomycin-C Applied by Intra-Tenon Injection Versus Sponge.

PURPOSE: To compare the outcomes of mitomycin-C (MMC) delivered by intra-Tenon injection vs sponge application during trabeculectomy surgery. METHODS: We retrospectively reviewed 566 patients with primary and secondary glaucoma diagnoses who received trabeculectomy surgery with MMC in an academic medical center. Exclusion criteria were age less than 18 years, no light perception vision, combined surgery, previous glaucoma incisional surgery, intraoperative 5-fluorouracil, or follow-up <1 month. Subjects were divided into 2 cohorts: MMC delivered by sponge application or by intra-Tenon injection. Main outcome measures were postoperative intraocular pressure (IOP) level and secondary measures were survival rate for IOP control, glaucoma medication use, complication rate, and vision. RESULTS: After inclusion/exclusion criteria, 316 eyes were available for analysis; 131 eyes had MMC delivered via sponge and 185 eyes via injection. Mean postoperative IOP was not significantly different between treatment groups but change in IOP from baseline was lower in the sponge vs the injection group 24 months after surgery (P = .038). The MMC sponge group had significantly more tense, vascularized, or encapsulated blebs as a late complication (P = .046). Time to failure for postoperative IOP control was not significantly different between MMC treatment groups, but older patient age and limbus-based conjunctival incision were associated with significantly longer time to fail. CONCLUSIONS: The application of MMC by injection was similar to application by sponge in lowering IOP in patients with glaucoma and the safety of both techniques appears to be comparable. Limbus-based conjunctival incision had longer time to failure for postoperative IOP control vs fornix-based incision. NOTE: Publication of this article is sponsored by the American Ophthalmological Society.

Immunoproteomic analysis of potential serum biomarker candidates in human glaucoma.

PURPOSE: Evidence supporting the immune system involvement in glaucoma includes increased titers of serum antibodies to retina and optic nerve proteins, although their pathogenic importance remains unclear. This study using an antibody-based proteomics approach aimed to identify disease-related antigens as candidate biomarkers of glaucoma. METHODS: Serum samples were collected from 111 patients with primary open-angle glaucoma and an age-matched control group of 49 healthy subjects without glaucoma. For high-throughput characterization of antigens, serum IgG was eluted from five randomly selected glaucomatous samples and analyzed by linear ion trap mass spectrometry (LC-MS/MS). Serum titers of selected biomarker candidates were then measured by specific ELISAs in the whole sample pool (including an additional control group of diabetic retinopathy). RESULTS: LC-MS/MS analysis of IgG elutes revealed a complex panel of proteins, including those detectable only in glaucomatous samples. Interestingly, many of these antigens corresponded to upregulated retinal proteins previously identified in glaucomatous donors (or that exhibited increased methionine oxidation). Moreover, additional analysis detected a greater immunoreactivity of the patient sera to glaucomatous retinal proteins (or to oxidatively stressed cell culture proteins), thereby suggesting the importance of disease-related protein modifications in autoantibody production/reactivity. As a narrowing-down strategy for selection of initial biomarker candidates, we determined the serum proteins overlapping with the retinal proteins known to be up-regulated in glaucoma. Four of the selected 10 candidates (AIF, cyclic AMP-responsive element binding protein, ephrin type-A receptor, and huntingtin) exhibited higher ELISA titers in the glaucomatous sera. CONCLUSIONS: A number of serum proteins identified by this immunoproteomic study of human glaucoma may represent diseased tissue-related antigens and serve as candidate biomarkers of glaucoma.

Rosai-dorfman disease diagnosed because of bilateral choroidal masses.

PURPOSE: To describe a case of bilateral choroidal masses leading to the diagnosis of Rosai-Dorfman disease. METHOD: Case report. Color photographs, fluorescein angiography, autofluorescence, indocyanine green angiography, and high-definition optical coherence tomography imaging of both eyes and computed tomography and biopsy of pelvis mass were performed. A 47-year-lady presented with unknown choroidal masses in both eyes. She had no visual complaints. Her medical history was noncontributory. RESULTS: Workup included a computed tomography of the chest and abdomen that demonstrated soft tissue masses in the renal pelvis bilaterally. A core needle biopsy from the renal mass demonstrated numerous histiocytoid that were positive for CD163 and S100 protein. CONCLUSION: Based on this spectrum of findings, the diagnosis of Rosai-Dorfman disease was made. To date, the patient has been followed-up for 3 years without medical intervention and without visual deterioration. Careful follow-up is a reasonable management if patients are asymptomatic.

Multifocal choroiditis secondary to the reactivation of epstein-barr virus.

PURPOSE: To describe a case of multifocal choroiditis associated with Epstein-Barr virus reactivation in a patient who had previously had documented infectious mononucleosis. METHODS: Color photos, fluorescein angiography, autofluorescence, indocyanine green angiography, and high-definition optical coherence tomography imaging was performed. A 39-year-old woman presented with a central scotoma in her left eye. At 19 years of age, she developed a peripapillary choroidal neovascular complex in her right eye, which was treated by laser photocoagulation. Two weeks before her visual complaint, she suffered from a frontal headache, occipital lymphadenopathy, and splenomegaly. RESULTS: Laboratory studies revealed markedly elevated immunoglobulin G titers to Epstein-Barr virus and she recalled a history of infectious mononucleosis at 20 years of age. CONCLUSION: While primary infection may manifest as infectious mononucleosis, like other viruses in the herpes virus family, there may be reactivation of the virus later in life.

Dorzolamide as an Effective Topical Therapy for Glaucoma in a Case of Nanophthalmos.

To report a case of nanophthalmos in which the intraocular pressure (IOP) off medication was 45 mm Hg and on dorzolamide hydrochloride once daily was 15 mm Hg for many years. No other medication affected the IOP. A chart review of a patient with nanophthalmos and glaucoma. A case of angle closure glaucoma in a nanophthalmic eye which had an unusually great and prolonged reduction of IOP secondary to the use of dorzolamide once daily, was reported.

Vagally mediated effects of glucagon-like peptide 1: in vitro and in vivo gastric actions.

Glucagon-like peptide-1 (GLP-1) is a neuropeptide released following meal ingestion that, among other effects, decreases gastric tone and motility. The central targets and mechanism of action of GLP-1 on gastric neurocircuits have not, however, been fully investigated. A high density of GLP-1 containing neurones and receptors are present in brainstem vagal circuits, suggesting that the gastroinhibition may be vagally mediated. We aimed to investigate: (1) the response of identified gastric-projecting neurones of the dorsal motor nucleus of the vagus (DMV) to GLP-1 and its analogues; (2) the effects of brainstem application of GLP-1 on gastric tone; and (3) the vagal pathway utilized by GLP-1 to induce gastroinhibition. We conducted our experiments using whole-cell recordings from identified gastric-projecting DMV neurones and microinjection in the dorsal vagal complex (DVC) of anaesthetized rats while monitoring gastric tone. Perfusion with GLP-1 induced a concentration-dependent excitation of a subpopulation of gastric-projecting DMV neurones. The GLP-1 effects were mimicked by exendin-4 and antagonized by exendin-9-39. In an anaesthetized rat preparation, application of exendin-4 to the DVC decreased gastric tone in a concentration-dependent manner. The gastroinhibitory effects of exendin-4 were unaffected by systemic pretreatment with the pro-motility muscarinic agonist bethanechol, but were abolished by systemic administration of the nitric oxide synthase (NOS) inhibitor N(G)-nitro-L-arginine methyl ester (L-NAME), or by bilateral vagotomy. Our data indicate that GLP-1 activates selective receptors to excite DMV neurones mainly and that the gastroinhibition observed following application of GLP-1 in the DVC is due to the activation of an inhibitory non-adrenergic, non-cholinergic input to the stomach.

Effects of brain stem cholecystokinin-8s on gastric tone and esophageal-gastric reflex.

The actions of cholecystokinin (CCK) on gastrointestinal functions occur mainly via paracrine effects on peripheral sensory vagal fibers, which engage vago-vagal brain stem circuits to convey effector responses back to the gastrointestinal tract. Recent evidence suggests, however, that CCK also affects brain stem structures directly. Many electrophysiological studies, including our own, have shown that brain stem vagal circuits are excited by sulfated CCK (CCK-8s) directly, and we have further demonstrated that CCK-8s induces a remarkable degree of plasticity in GABAergic brain stem synapses. In the present study, we used fasted, anesthetized Sprague-Dawley rats to investigate the effects of brain stem administration of CCK-8s on gastric tone before and after activation of the esophageal-gastric reflex. CCK-8s microinjected in the dorsal vagal complex (DVC) or applied on the floor of the fourth ventricle induced an immediate and transient decrease in gastric tone. Upon recovery of gastric tone to baseline values, the gastric relaxation induced by esophageal distension was attenuated or even reversed. The effects of CCK-8s were antagonized by vagotomy or fourth ventricular, but not intravenous, administration of the CCK-A antagonist lorglumide, suggesting a central, not peripheral, site of action. The gastric relaxation induced by DVC microinjection of CCK-8s was unaffected by pretreatment with systemic bethanecol but was completely blocked by NG-nitro-L-arginine methyl ester, suggesting a nitrergic mechanism of action. These data suggest that 1) brain stem application of CCK-8s induces a vagally mediated gastric relaxation; 2) the CCK-8s-induced gastric relaxation is mediated via activation of nonadrenergic, noncholinergic pathways; and 3) CCK-8s reverses the esophageal-gastric reflex transiently.

Effects of chronic spinal cord injury on body weight and body composition in rats fed a standard chow diet.

The inability to maintain body weight within prescribed ranges occurs in a significant portion of the human spinal cord injury (SCI) population. Using a rodent model of long-term high thoracic (spinal level T3) spinal cord transection (TX), we aimed to identify derangements in body weight, body composition, plasma insulin, glucose tolerance, and metabolic function, as measured by uncoupling protein 1 (UCP1) expression in interscapular brown adipose tissue (IBAT). Sixteen weeks after SCI, body weights of injured female rats stabilized and were significantly lower than surgical control animals. At the same time point, SCI rats had a significantly lower whole body fat:lean tissue mass ratio than controls, as measured indirectly by NMR. Despite lower body weight and fat mass, the cumulative consumption of standard laboratory chow (4.0 kcal/g) and mean energy intake (kcal.day(-1).100 g body wt(-1)) of chronic SCI rats was significantly more than controls. Glucose tolerance tests indicated a significant enhancement in glucose handling in 16-wk SCI rats, which were coupled with lower serum insulin levels. The post mortem weight of gonadal and retroperitoneal fat pads was significantly reduced after SCI and IBAT displayed significantly lower real-time PCR expression of UCP1 mRNA. The reduced fat mass and IBAT UCP1 mRNA expression are contraindicative of the cumulative caloric intake by the SCI rats. The prolonged postinjury loss of body weight, including fat mass, is not due to hypophagia but possibly to permanent changes in gastrointestinal transit and absorption, as well as whole body homeostatic mechanisms.

Subconjunctival sodium hyaluronate 2.3% in trabeculectomy: a prospective randomized clinical trial.

PURPOSE: To investigate the efficacy of subconjunctival sodium hyaluronate 2.3% in increasing the success rate of glaucoma filtering surgery and promoting filtering blebs with characteristics presumed to predict better success. DESIGN: Randomized controlled clinical trial. PARTICIPANTS: Fifty-five patients scheduled for glaucoma surgery. INTERVENTION: Patients underwent routine trabeculectomy, with or without phacoemulsification and intraocular lens implantation. In the study group (n = 28), sodium hyaluronate 2.3% was injected between the scleral and conjunctival flaps at the conclusion of the surgery. In the control group (n = 27), balanced salt solution (BSS) was injected in the same fashion, in an unmasked design. MAIN OUTCOMES MEASURES: Surgical success was defined as (1) a complete success if the intraocular pressure (IOP) was 21 mmHg or less without any antiglaucoma medication, and (2) a qualified success if the IOP was 21 mmHg or less, with or without antiglaucoma medication. Patients requiring additional surgery, including needling, or with IOP more than 21 mmHg, even when receiving antiglaucoma medications, were considered to have failed treatment. Success rates in both groups were compared using Kaplan-Meier survival curves and the log-rank test. The morphologic characteristics of the filtering blebs were evaluated using the Indiana Bleb Appearance Grading Scale. Other outcome measures were IOP, visual acuity, need for antiglaucoma medication, and any complications. RESULTS: Fifty-two patients completed the study (27 in the study group and 25 in the control group), with a mean follow-up of 12.3 months. Complete success rates were 77.8% for the study group and 84.0% for the control group 12 months after surgery (P>0.5); qualified success rates were 88.9% for the study group and 92.0% for the control group (P>0.6). Mean IOP decreased from 26.0+/-10.0 mmHg to 11.6+/-4.1 mmHg in the study eyes (P<0.001) and from 24.9+/-9.7 mmHg to 13.0+/-4.1 mmHg in the control eyes (P<0.001). Intraocular pressure measurements in both groups were similar at all visits (P>0.05). The study eyes had more diffuse blebs than the control eyes (62.5% > or =4 clock-hours vs. 22.7%; P = 0.012). Postoperative complications were similar in the study eyes (14.8%) and the control eyes (20.0%; P>0.6). CONCLUSIONS: There was no difference in success rates in patients who received subconjunctival sodium hyaluronate 2.3% compared to BSS injections. Subconjunctival sodium hyaluronate 2.3% was associated with more diffuse blebs after filtering surgery.