Theophylline toxicity: Successful management of a patient with distributive shock secondary to drug overdose.

Presenting a case of acute theophylline and salbutamol overdose with distributive shock. Twenty one years old lady presented with history of consumption of 3 gram of theophylline and 40 mg of salbutamol. On admission she had altered sensorium with the systolic blood pressure of 60 mmHg, unrecordable diastolic blood pressure and heart rate of 147/min. Investigations revealed severe metabolic acidosis, hypokalemia, hypocalcemia which was managed by intravenous fluids, vasopressors, infusion of injection calcium gluconate and injection potassium chloride. As her hemodynamic status did not improve, she has been initiated on 1.5 mL/kg of lipid emulsion as bolus and then 0.5 mL/kg/h as infusion. Her hemodynamic status improved gradually and she was discharged in 24 h. Lipid emulsion had been used in local anesthetics and many tablet overdoses. In this patient timely administration of lipid emulsion resulted in early recovery of shock.

Blockade of the VEGF isoforms in inflammatory corneal hemangiogenesis and lymphangiogenesis.

BACKGROUND: The VEGF-A family plays a crucial role in the induction of pathological corneal neovascularization. The role of the different VEGF-A isoforms during lymphangiogenesis is only little-known. Current anti-angiogenic therapies in the eye and other organs inhibit all VEGF-A isoforms, and have effects on both blood and lymphatic vessels. Here we investigate whether selective targeting of the isoform VEGF 165 is able to inhibit corneal lymphangiogenesis under inflammatory conditions. METHODS: The mouse model of suture-induced corneal neovascularization was used to assess the antihem- and antilymphangiogenic effect of topically applied pegaptanib. Corneal blood and lymph vascularized areas were analyzed morphometrically. Furthermore, we analyzed the proliferative effects of VEGF A 121, 165, and 189 on blood and lymphatic endothelial cells (BEC/LEC) via a cell-proliferation assay. RESULTS: Pegaptanib significantly inhibited inflammatory corneal hemangiogenesis (p < 0.01), but not lymphangiogenesis in vivo (p > 0.05), both topically as well as systemically, in the inflamed cornea. In vitro, BECs were more susceptible to pegaptanib than LECs. CONCLUSIONS: Targeting VEGF-A 165 significantly inhibits hem- but not lymphangiogenesis, suggesting VEGF-A 165 to be critical for hem-, but dispensable for lymphangiogenesis, at least in the inflamed cornea.

Topical Ranibizumab inhibits inflammatory corneal hem- and lymphangiogenesis.

PURPOSE: Ranibizumab (Lucentis(®) ) is a Fab-Fragment of a recombinant, humanized, monoclonal VEGF (anti-vascular endothelial growth factor) antibody. This study analyzed the ability of topical Ranibizumab to inhibit lymphangiogenesis in addition to hemangiogenesis after acute corneal inflammation in vivo. In addition, the effect of Ranibizumab on the proliferation of human lymphatic endothelial cells (LECs) and blood endothelial cells (BECs) in vitro was studied. METHODS: The inhibitory effect of Ranibizumab on LECs and BECs was studied in vitro using a proliferation enzyme-linked immunosorbent assay (ELISA) assay. To study the in vivo effects of Ranibizumab, the mouse model of suture induced inflammatory corneal neovascularization was used. Study mice received topical Ranibizumab as eye drops. After 1 week excised corneas were stained with LYVE-1 and CD31. Hemangiogenesis and lymphangiogenesis were analyzed morphometrically by using a semiautomatic method based on the image analyzing program Cell^F. RESULTS: An antiproliferative effect of Ranibizumab was seen in vitro on both human BECs and LECs with a significance of p < 0.0001 and p < 0.0004, respectively. In vivo experiments showed that topical application of Ranibizumab significantly inhibits both hemangiogenesis (p = 0.0026) and lymphangiogenesis (p = 0.0026) in the cornea. CONCLUSION: Ranibizumab is a potent inhibitor of inflammatory corneal hemangiogenesis and lymphangiogenesis in vivo with a direct inhibitory effect on both endothelial cell types in vitro. This study for the first time demonstrates an inhibitory effect of Ranibizumab on lymphatic vessels which could have a wider range of clinical applications.

Photophysics and light-activated biocidal activity of visible-light-absorbing conjugated oligomers.

The photophysical properties of three cationic π-conjugated oligomers were correlated with their visible light activated biocidal activity vs S. aureus. The oligomers contain three arylene units (terthiophene, 4a; thiophene-benzotriazole-thiophene, 4b; thiophene-benzothiadiazole-thiophene, 4c) capped on each end by cationic -(CH2)3NMe3(+) groups. The oligomers absorb in the visible region due to their donor-acceptor-donor electronic structure. Oligomers 4a and 4b have high intersystem crossing and singlet oxygen sensitization efficiency, but 4c has a very low intersystem crossing efficiency and it does not sensitize singlet oxygen. The biocidal activity of the oligomers under visible light varies in the order 4a > 4b ≈ 4c.

Glaucoma management in patients with osteo-odonto-keratoprosthesis (OOKP): the Singapore OOKP Study.

PURPOSE: To report diagnostic modalities and treatment options for glaucoma in eyes with osteo-odonto keratoprosthesis (OOKP). METHODS: Eyes that underwent OOKP were evaluated for glaucoma at the time of the first postoperative visit, then at 1 and 3 months after the procedure, and thereafter every 6 months. All eyes underwent stereo-biomicroscopic optic nerve head (ONH) assessment, kinetic (Goldmann perimetry) and automated static visual field testing, ONH photography, Heidelberg retina tomograph, scanning laser polarimetery (GDx), and optical coherence tomography. Treatment of glaucoma was also reviewed. RESULTS: Average follow-up period was 19.1 (range: 5 to 31) months. Of the 15 eyes that underwent OOKP, 5 eyes had preexisting glaucoma. None of the other 10 eyes developed glaucoma after OOKP. ONH photography and visual field testing were the most reliable methods to assess status of the disease, whereas Heidelberg retina tomograph and optical coherence tomography could be performed with reasonable reproducibility and quality; GDx imaging was poor. All patients with glaucoma were treated with oral acetazolamide 500 mg twice a day. Transscleral cyclophotocoagulation was performed in 3 eyes at stage 2 of OOKP surgery. Progression of glaucoma was noted in 2 eyes on the basis of optic disc photographs and automated perimetry. CONCLUSIONS: Visual field testing and optic disc assessment with optic disc photographs seem to be effective methods to monitor eyes with OOKP for glaucoma. Treatment strategies include oral medications to lower intraocular pressure and cyclophotocoagulation.

Corneal (lymph)angiogenesis--from bedside to bench and back: a tribute to Judah Folkman.

The normal cornea, the transparent "windscreen" of the eye, is devoid of both blood and lymphatic vessels. Nevertheless, both hem- and lymphangiogenesis can occur in response to severe corneal inflammation and can lead to blindness. Judah Folkman and co-workers exceedingly used the normally avascular cornea as the in vivo model system to study the mechanisms of angiogenesis and to test activators and inhibitors of angiogenesis in the last 3 decades. Recently, the cornea also became a successful model to study especially inflammatory lymphangiogenesis. As the last step in the circle from bedside to bench and back, we now are seeing the first (usually off-label) use of specific novel angiogenesis inhibitors in the diseased and pathologically vascularized human cornea to treat sight-threatening corneal angiogenesis and to promote graft survival after corneal transplantation by inhibiting lymphangiogenesis.

Keratoprosthesis surgery for end-stage corneal blindness in asian eyes.

PURPOSE: To establish a multidisciplinary surgical program for osteo-odonto-keratoprosthesis (OOKP) surgery in Asia and to evaluate efficacy and preliminary safety of this keratoprosthesis in end-stage corneal and ocular surface disease. DESIGN: Prospective noncomparative case series. PARTICIPANTS: Sixteen adults of Asian ethnic origin, bilaterally blind with end-stage corneal blindness from Stevens-Johnson syndrome, or severe chemical or thermal burns. METHODS: Osteo-odonto-keratoprosthesis surgery involves 2 procedures-in stage 1, an autologous canine tooth is removed, modified to receive an optical polymethyl methacrylate cylinder, and implanted into the cheek. The ocular surface is denuded and replaced with full-thickness buccal mucosa. Stage 2 surgery, performed 2 to 4 months later, involves retrieval of the tooth-cylinder complex and implanting it into the cornea, after reflection of the buccal mucosal flap, corneal trephination, iris and lens removal, and anterior vitrectomy. Concurrent glaucoma and vitreoretinal procedures are also performed at either stage, as required. MAIN OUTCOME MEASURES: Visual acuity (VA), field of vision, anatomical integrity and stability, and ocular and oral complications related or unrelated to the OOKP device. RESULTS: Osteo-odonto-keratoprosthesis surgery was performed on 15 patients, with a mean follow-up of 19.1 months (range, 5-31). Intraoperative complications included expulsive hemorrhage (keratoprosthesis device not implanted), tooth fracture (n = 1), oronasal fistula (n = 1), and mild inferior optic tilt (n = 1). Anatomical stability and keratoprosthesis retention has been maintained in all eyes, with no dislocation, extrusion, retroprosthetic membrane formation, or keratoprosthesis-related infection. Other complications not directly related to device insertion included retinal detachment (RD) related to silicone oil removal (n = 1) and endophthalmitis related to endoscopic cyclophotocoagulation performed 1 year after OOKP surgery (n = 1). Eleven patients (73.3%) attained a stable best spectacle-corrected VA of at least 20/40 or better, whereas 9 (60%) attained stable 20/20 vision. Four patients achieved their best visual potential, ranging from 20/100 to counting fingers vision, related to preexisting glaucomatous optic neuropathy or previous RD. CONCLUSIONS: Establishment of our OOKP program suggests that OOKP surgery has the potential to restore good vision to the most severe cases of corneal blindness in an Asian setting, with minimal device-related complications. Longer follow-up of these cases is currently underway.

Outcomes of femtosecond laser-assisted penetrating keratoplasty.

PURPOSE: To evaluate outcomes from the use of a femtosecond laser to trephine both donor and recipient corneas during penetrating keratoplasty (PK). DESIGN: Prospective interventional case series. METHODS: Patients were recruited from the cornea clinic of the Singapore National Eye Centre. We used a 10-kHz Femtec (20/10 Perfect Vision, Heidelberg, Germany) femtosecond laser to perform trephination of the donor cornea on an artificial anterior chamber, followed by trephination of the recipient cornea. Trephination cuts were straight and performed 90 degrees to the corneal surface. Tissue bridges were bluntly separated with a Barrett phaco chopper. The donor button was then sutured to the recipient with double continuous sutures, or interrupted sutures if significant host corneal vascularization was present. Postoperatively, visual acuity, refraction, intraocular pressures, and optical coherence tomography (Visante; Carl Zeiss, Jena, Germany) were evaluated. RESULTS: Eight eyes of eight patients underwent PK for conditions ranging from bullous keratopathy to corneal scarring from herpetic stromal keratitis. Patients were followed up for a mean of 9.5 months. Best-corrected visual acuities of patients with no ocular comorbidity ranged from 20/20 to 20/80. Mean cylindrical refractive error at last review was 2.56 diopters [D] (range, 0.50 to 4.00 D). Tissue bridges were bluntly dissected except for one case that required scissors completion of trephination. No complications were encountered related to use of the Femtec laser. CONCLUSION: The Femtec laser reliably trephines both donor and recipient corneas for PK, with good visual outcomes and relatively low degrees of astigmatism.

Adjuvant radiotherapy in incompletely staged IC and II endometrioid uterine cancer.

OBJECTIVES: To estimate if adjuvant radiotherapy improves the disease-specific survival of patients with clinical stage IC and II endometrioid corpus cancer who did not undergo lymphadenectomy. METHODS: Information was obtained on patients with endometrioid corpus cancer from the National Cancer Institute database between 1988 and 2001. Data were analyzed using Kaplan-Meier and Cox proportional hazards regression methods. RESULTS: A total of 3,664 patients (median age 70 years) with clinical stage IC to II endometrioid carcinoma did not undergo lymphadenectomy, of which 2,170 had stage IC and 1,494 stage II disease. Of these, 1,175 had grade 1, 1,637 had grade 2, 693 had grade 3, and in 159, grade was unknown. The 5-year disease-specific survival rates of clinical stage IC compared with stage II patients were 91.3% and 86.7% (P<.001). Of the 1,964 who received adjuvant radiotherapy, the 5-year disease-specific survival rate was 89.9% compared with 87.8% in those who did not undergo further treatment (P=.04). Adjuvant radiation improved the disease-specific survival rate of those with stage II disease, (86.5% compared with 81.9%; P=.02), but not in those with stage IC disease (91.7% compared with 92.6%; P=.68). The benefit of radiotherapy was significant in patients with grade 3 disease and patients 70 years or older (88.2% compared with 83.3%; P<.001). On multivariable analysis, age, stage, and grade were significant independent prognostic factors for disease-specific survival. CONCLUSION: Adjuvant radiotherapy marginally improved the survival of clinically staged IC-II endometrioid uterine cancer patients without lymphadenectomy. After excluding those without hysterectomy, radiotherapy did not significantly affect disease-specific survival. LEVEL OF EVIDENCE: II.

Infectious keratitis after laser epithelial keratomileusis.

PURPOSE: To report two cases of infectious keratitis occurring after laser epithelial keratomileusis (LASEK). METHODS: Two patients who underwent LASEK were referred to our center for the management of postoperative infectious keratitis. Infection occurred on postoperative days 2 (case 1) and 5 (case 2). Presenting visual acuity was count fingers in both cases. RESULTS: Patients were treated aggressively with hourly topical broad-spectrum fortified antibiotics after corneal scrapings were obtained. Culture was positive for Staphylococcus aureus in case 2. Both eyes responded to treatment, resulting in residual corneal scarring with reduced best spectacle-corrected visual acuity of 20/40 in case 1 and uncorrected visual acuity of 20/25 in case 2. CONCLUSIONS: Infectious keratitis can occur after LASEK surgery, and early diagnosis and aggressive therapy are required to aser ereduce visual loss.

Deep lamellar keratoplasty for acanthamoeba keratitis.

PURPOSE: To describe deep lamellar keratoplasty (DALK) as a surgical alternative to penetrating keratoplasty in the management of unresponsive Acanthamoeba keratitis. METHODS: Interventional case report. We performed DALK in a patient with Acanthamoeba keratitis unresponsive to intensive antimicrobial therapy. A modified form of the Anwar big-bubble technique, with total corneal stromal removal down to Descemet membrane, was successfully performed without entry into the anterior chamber. Subsequent delay in graft epithelialization relating to ocular surface toxicity from prolonged antiacanthamoebal topical therapy required a secondary amniotic membrane patch graft. RESULTS: No recurrence of Acanthamoeba infection occurred after surgery. Reepithelialization after the amniotic membrane patch graft was successful, and full visual recovery occurred, resulting in a best-corrected visual acuity of 20/20. CONCLUSIONS: DALK with total removal of infected stromal tissue may be performed in medically unresponsive cases of Acanthamoeba keratitis, which ordinarily may require penetrating keratoplasty. Advantages of DALK in infectious keratitis include less risk of intraocular entry of infectious organisms at the time of surgery and the potential for improved graft survival rates caused by less endothelial rejection and failure.

The benefit of adjuvant radiation therapy in single-node-positive squamous cell vulvar carcinoma.

OBJECTIVE: To determine if adjuvant radiotherapy improves the survival of women with invasive squamous cell carcinoma of the vulva involving one inguinal node. METHODS: Demographic, pathologic, and treatment information was obtained on patients with vulvar cancers from the Surveillance, Epidemiology, and End Results database between 1988 and 2001. Kaplan-Meier estimates and Cox-proportional hazards model were used for analyses. RESULTS: Of the 490 patients with stage III, node-positive vulvar cancers, 208 had a single positive inguinal node. The median age of this group was 71 years (range: 29-100). 82.2% of patients were White, 7.2% were Hispanic, 7.7% were Black, 1.4% were Asian, and 1.4% were Others. 91.8% of patients underwent a radical vulvectomy with a unilateral or bilateral inguinal lymphadenectomy. The median number of lymph nodes resected was 13 (range: 1-34). 102 women underwent adjuvant radiotherapy, while 106 did not receive any radiation treatment. Women who received adjuvant radiotherapy had a 5-year disease-specific survival of 77.0% compared to 61.2% in those without radiotherapy (p=0.02). After stratifying the study group based on the extent of lymphadenectomy, we found that radiation treatment improved the survival of those with