Radiation induced violations of blood circulation in the ciliary body and changes of the anterior chamber angle in the pathogenesis of glaucoma in clean up workers of the Chornobyl NPP accident and residents of contaminated areas. / RADITsIY̆NO INDUKOVANI PORUShENNIa KROVOOBIGU V TsILIARNOMU TILI TA ZMINY KUTA PEREDN'OI KAMERY OKA V PATOGENEZI GLAUKOMY V UChASNYKIV AVARIY̆NYKh ROBIT NA ChORNOBYL'S'KIY̆ AES I MEShKANTsIV ZABRUDNENYKh TERYTORIY̆.

OBJECTIVE: Estimate changes blood filling of the ciliary body and changes of the anterior chamber angle; study their influence to glaucoma pathogenesis in irradiated persons. MATERIALS AND METHODS: Used the results of a randomly selected group survey of 41 clean up workers of the Chornobyl NPP accident (clean up workers), and 18 inhabitants of the zone of guaranteed voluntary resettlement; age at the time of the survey was 45-50 years. The control group consisted of 41 persons of the same age had not radiation exposure. State of the anterior chamber angle studied by gonioscopy, which was conducted 35 clean up workers and 35 persons of the control group. Changes of the blood circulation in the ciliary body examine by the ophtalmoreog raphy, what was done on 12 eyes of 6 clean up workers, control was 12 eyes of 6 persons had not radiation exposure. RESULTS: Detection revealed of the blood circulation in the ciliary body in all clean up workers, reography coefficient was probably lower (p < 0.05), than in the control group. The research of the state of the anterior chamber angle revealed a higher relative risk of appearance of involution changes of the anterior chamber angle in clean up work ers of ChNPP accident, in comparison with the control group was 3.5 (1.27; 9.5) χ2 = 7.48, p = 0.031. The same changes are characteristic for inhabitants of radiation polluted territories. CONCLUSIONS: Influence ionizing radiation causes a blood circulation decrease in the ciliary body and development changes of the angle of the anterior chamber. Presence of these changes can explain the features of the pathogene sis of glaucoma in irradiated late manifestation and, at the same time, severe course.

Platelet activation by ADP is increased in selected patients with anterior ischemic optic neuropathy or retinal vein occlusion.

To investigate whether adenosine diphosphate (ADP)-induced platelet hyperaggregability is associated with nonarteritic anterior ischemic optic neuropathy (NAION) or retinal vein occlusion (RVO). We retrospectively reviewed thrombophilia screening data of patients with NAION or RVO without a history of arterial hypertension, diabetes mellitus, hyperlipidemia, obesity, and cigarette abuse. Patients with a positive family history for thromboembolism were not excluded. Platelet aggregation (area under the curve, AUC) after induction of 0.5, 1.0, and 2.0 µmol of ADP was estimated in 25 NAION and RVO patients and compared with 25 healthy controls. We observed significantly greater platelet aggregation post 0.5 (P = 0.002) and 1.0 (P = 0.008) µmol of ADP among NAION and RVO patients compared with healthy controls. Platelet hyperaggregability was significantly more prevalent in patients than in controls (56% vs. 8%; P = 0.0006). Our results suggest that in NAION and RVO patients without a history of arterial hypertension, diabetes mellitus, hyperlipidemia, obesity, and cigarette abuse, platelets are significantly hyperreactive after induction of very low concentrations of ADP when compared with healthy individuals. This hyperreactivity is particularly evident in patients with a family history of thromboembolism.

Efficacy and safety of intravitreal bevacizumab in eyes with neovascular glaucoma undergoing Ahmed glaucoma valve implantation: 2-year follow-up.

PURPOSE: To evaluate the efficacy and safety of intravitreal bevacizumab (IVB) in eyes with neovascular glaucoma (NVG) undergoing Ahmed glaucoma valve (AGV) implantation. METHODS: This was a multicentre, prospective, randomized clinical trial that enrolled 40 patients with uncontrolled neovascular glaucoma that had undergone panretinal photocoagulation and required glaucoma drainage device implantation. Patients were randomized to receive IVB (1.25 mg) or not during Ahmed valve implant surgery. Injections were administered intra-operatively, and 4 and 8 weeks after surgery. RESULTS: After a mean follow-up of 2.25 ± 0.67 years (range 1.5-3 years), both groups showed a significant decrease in IOP (p < 0.05). There was no difference in IOP between groups except at the 18-month interval, when IOP in IVB group was significantly lower (14.57 ± 1.72 mmHg vs. 18.37 ± 1.06 mmHg - p = 0.0002). There was no difference in survival success rates between groups. At 24 months, there was a trend to patients treated with IVB using less antiglaucoma medications than the control group (p = 0.0648). Complete regression of rubeosis iridis was significantly more frequent in the IVB group (80%) than in the control group (25%) (p = 0.0015). CONCLUSIONS: Intravitreal bevacizumab may lead to regression of new vessels both in the iris and in the anterior chamber angle in patients with neovascular glaucoma undergoing Ahmed glaucoma valve implantation. There is a trend to slightly lower IOPs and number of medications with IVB use during AGV implantation for neovascular glaucoma.

Relationship between sleep-disordered breathing and iris and/or angle neovascularization in proliferative diabetic retinopathy cases.

PURPOSE: To investigate whether sleep-disordered breathing is a risk factor for iris and/or angle neovascularization in patients with proliferative diabetic retinopathy (PDR). DESIGN: Cross-sectional comparative case series. SUBJECTS AND METHODS: One hundred fifty-one consecutive patients with PDR who underwent surgery in our hospital were divided based on the presence of iris and/or angle neovascularization (NV group, 37 patients) or absence of NV (non-NV group, 114 patients). Pulse oximetry was conducted during the night and the mean SpO(2), 4% oxygen desaturation index (4% ODI times/hour), the lowest SpO(2)% during sleep (lowest SpO(2)), and the cumulative percentage of time at SpO(2) <90% in analysis times (CT90%) were calculated. When the 4% ODI exceeded 5 times/hour, sleep-disordered breathing was diagnosed. The results were compared between the 2 groups. Preoperative systemic parameters also were analyzed by logistic regression to clarify risk factors for the NV group. RESULTS: A mean total of 50% (62% of the NV group and 46% of the non-NV group) was diagnosed with sleep-disordered breathing. The mean SpO(2) and lowest SpO(2) did not differ significantly between the 2 groups; the 4% ODI (12.3 vs 6.6) and CT90% (3.8 vs 1.7) were significantly higher in the NV group (P=.02, for both comparisons). Logistic regression analysis identified insulin therapy (odds ratio [OR], 3.01; 95% confidence interval [CI], 1.26∼7.20; P=.01); and 4% ODI (OR, 1.09; CI, 1.01∼1.16; P=.02) as risk factors for the NV group. CONCLUSIONS: In patients with PDR, nocturnal intermittent hypoxia/reoxygenation resulting from sleep-disordered breathing may be a risk factor for iris and/or angle neovascularization.

Evaluation of cytotoxicity of bevacizumab on VEGF-enriched corneal endothelial cells.

PURPOSE: To evaluate the cytotoxicity of varying doses of Bevacizumab on corneal endothelial cells in the presence of a range of concentrations of vascular endothelial growth factor (VEGF). Bevacizumab, a drug widely used in the treatment of neovascular glaucoma neutralizes all isoforms of VEGF and ameliorates neovascularization after intracameral administration. However, the safety of intracameral administration of Bevacizumab and dose-dependent toxicity on corneal endothelial cells has not been established. METHODS: Bovine corneal endothelial (BCE) cells were treated with VEGF (50 ng/ml) and/or Bevacizumab (0.1-2 mg/ml) for 72 h. Cell proliferation was measured with the water soluble tetrazolium salts (WST-1) assay. Morphological changes were recorded by bright-field microscopy of cells. Cytotoxicity in response to Bevacizumab was evaluated by trypan blue exclusion, as well as annexin V/propidium iodide (PI) staining. RESULTS: Bevacizumab was not cytotoxic at the concentrations tested and the percentage of Bevacizumab-treated cells staining positively for both PI and Annexin V was less than 1%. The anti-proliferative effects of Bevacizumab on BCE cells were dose-dependent; a dose of 1.5 mg/ml or 2 mg/ml produced a 33% (p=0.005) or 47% (p=0.001) decrease in cell proliferation compared to controls. Similar results were obtained in cells treated with a combination of Bevacizumab and VEGF. VEGF (50 ng/ml) had no significant effect on cell proliferation compared to controls. Morphology of cells was unchanged after treatment with Bevacizumab and/or VEGF compared to controls. CONCLUSIONS: Bevacizumab was safe and not toxic to BCE cells at concentrations commonly used in clinical practice.

Anterior chamber blood reflux during trabeculectomy in an eye with previous trabectome surgery.

INTRODUCTION: The Trabectome is a novel surgical device used in the treatment of open angle glaucoma that removes trabecular meshwork tissue to improve aqueous access to drainage channels. Little is known about the long-term consequences of permanently unroofing Schlemm canal. Eyes that have had previous surgery in the iridocorneal angle, specifically permanent removal of trabecular meshwork tissue, may have an increased propensity for blood reflux. CASE PRESENTATION: We present a case of a patient who had intraoperative blood reflux onto peripheral iris during trabeculectomy 11 months after Trabectome surgery. DISCUSSION: Intraoperative blood reflux and resultant hyphema is strongly correlated with Trabectome surgery, but the literature does not reveal any cases of late postoperative blood reflux. In our patient, the absence of overlying angle structures, including the roof of Schlemm canal, may have allowed blood to reflux into the angle and onto peripheral iris during a sudden decrease in intraocular pressure in trabeculectomy surgery. Further studies to assess the consequences of permanent trabecular meshwork tissue removal may be warranted.

Intracameral injection of bevacizumab (Avastin) to treat anterior chamber neovascular membrane in a painful blind eye.

Intracameral injection of bevacizumab (Avastin) helped in the successful regression of an anterior chamber neovascular membrane in a painful blind eye. The effect was persistent even after six months of follow-up. This is the first report on intracameral administration of bevacizumab with six months of follow-up.

Iris and anterior chamber angle neovascularization after iodine 125 brachytherapy for uveal melanoma.

PURPOSE: Iris neovascularization (INV) and anterior chamber angle neovascularization after radiotherapy for uveal melanoma may lead to neovascular glaucoma and enucleation. However, neovascularization of the anterior ocular segment may respond favorably to treatment with panretinal photocoagulation. The purpose of this study was to evaluate the frequency, interval to development, and predisposing factors of anterior ocular segment neovascularization following iodine 125 (I125) brachytherapy for uveal melanoma. DESIGN: Retrospective, interventional, consecutive case series. PARTICIPANTS: Sixty-five patients (65 eyes), consecutively treated with I125 brachytherapy for uveal melanoma from 1995 through 2000 and followed up after radiation therapy for 24 months or more. METHODS: Clinical findings and ultrasonography characteristics as well as treatment parameters were analyzed. MAIN OUTCOME MEASURES: The frequency of INV was determined and the interval to development of INV as well as the predisposing factors were analyzed statistically. RESULTS: In 15 of 65 eyes (23%), INV was detected after I125 brachytherapy at a mean +/- standard deviation of 26.66+/-11.63 months (median, 24 months; range, 9-48 months). Risk factors displaying the stronger correlation with INV were greater maximal tumor height (P<0.01), greater tumor vascularity (P<0.01), and disinsertion of horizontal rectus muscles (P = 0.01). CONCLUSIONS: After I125 brachytherapy for choroidal melanoma, INV developed in 23% of eyes and was correlated with larger tumor size, greater tumor vascularity, and disinsertion of a horizontal rectus muscle.

Short-term blood-aqueous barrier breakdown after implantation of the 1CU accommodative posterior chamber intraocular lens.

PURPOSE: To quantify intraocular inflammation after phacoemulsification with implantation of an accommodative posterior chamber intraocular lens (IOL). SETTING: Department of Ophthalmology, University of Erlangen-Nürnberg, Erlangen, Germany. METHODS: Twenty cataractous eyes of 20 patients without preexisting blood-aqueous barrier (BAB) deficiencies or previous intraocular surgery were included in this study. The mean age of the patients was 64.6 years +/- 16.0 (SD). A single surgeon performed phacoemulsification through a superior sclerocorneal tunnel incision and implantation of a 1CU IOL (HumanOptics AG) though a 3.2 mm incision. The haptics of the single-piece acrylic 1CU lens are designed for anterior optic movement following ciliary muscle contraction. The postoperative treatment was standardized. Postoperative BAB breakdown was quantified by laser flare photometry (FC-1000, Kowa) at 1 day, 1 and 4 weeks, and 3 and 6 months. RESULTS: The mean aqueous flare was 6.3 photons/ms +/- 3.0 (SD) (range 4.0 to 12.2 photons/ms) 1 day postoperatively, with 64% of patients having normal aqueous flare values (<8.0 photons/ms). One week after surgery, the mean aqueous flare was 5.3 +/- 2.8 photons/ms (range 2.0 to 10.5 photons/ms). Four weeks postoperatively, aqueous flare was normal in all patients and remained stable below the normal limit for up to 6 months (mean 3.3 +/- 1.2 months; range 2.0 to 5.4 months). The number of aqueous cells did not increase at any follow-up and was normal in all eyes. No postoperative complications such as fibrin formation, synechias, macrophages on the IOL optic, or endophthalmitis were observed. CONCLUSIONS: Phacoemulsification with implantation of the 1CU accommodative IOL led to minimal and short-lasting BAB alteration. No signs of persistent inflammation or pigment dispersion were detected.

Recurrent hyphema in an aphakic child: Swan syndrome.

In 1973, Swan described 3 patients who developed hyphema months to years after uncomplicated cataract surgery. He noted focal vascularization from an ingrowth of episcleral vessels at the cataract wound site, resulting in recurrent intraocular bleeding. Swan syndrome has been reported following intracapsular cataract extraction, extracapsular cataract extraction (including clear corneal incisions), iridocyclectomy, and glaucoma filtering procedures. Patients typically present with sudden painless blurred vision, often upon awakening, which may or may not be preceded by physical strain or trauma. Other patients are asymptomatic and diagnosed with hyphema or anterior chamber red blood cells on routine examination. The hyphema often resolve spontaneously, making later diagnosis difficult. Gonioscopic visualization of the abnormal wound vessels is necessary for diagnosis. Without active bleeding, however, the fibrovascular tuft may be easily overlooked. We report a case of Swan syndrome in a 16-month-old boy after cataract extraction was performed. To our knowledge, Swan syndrome has not been reported in the pediatric population. Children represent a significant proportion of patients undergoing anterior segment surgery and Swan syndrome should be considered in the differential diagnosis of hyphema in this population.

Macrophages induce apoptosis in normal cells in vivo.

It is well established that macrophages have a function in scavenging apoptotic bodies from cells undergoing programmed cell death. Here we show that macrophages can also induce apoptosis of normal cells. Using injected toxic liposomes to eliminate macrophages in the anterior chamber of the rat eye, we provide direct evidence that, in vivo, macrophages induce apoptosis in normal vascular endothelial cells during programmed capillary regression. Macrophage elimination resulted in the survival of endothelial cells that normally would die and the persistence of functional capillaries. Furthermore, replacement of eliminated macrophages with bone-marrow-derived macrophages 'rescued' lack of capillary regression. Viability of the persistent target cells was demonstrated through their lack of apoptotic morphology, expression of intracellular esterases and synthesis of DNA. These results uncover a new function for macrophages in the remodeling of tissues through the induction of programmed cell death and provide direct evidence of a key role for macrophages in capillary regression.

Effect of 3.0 mm tunnel and 6.0 mm corneoscleral incisions on the blood-aqueous barrier.

PURPOSE: To study of the effect of silicone intraocular lens (IOL) implantation using a 3.0 mm tunnel incision with that of implantation though a 6.0 mm corneoscleral incision after phacoemulsification in human eyes. SETTING: Department of Ophthalmology, University of Köln, Germany. METHODS: In a prospective, randomized clinical study, 50 patients with senile cataract had phacoemulsification and IOL implantation through a 3.0 mm tunnel or a 6.0 mm corneoscleral incision. To assess blood-aqueous barrier (BAB) disruption, preoperative and postoperative sodium fluorescein concentrations in the anterior chamber were measured with the Fluorotron Master II. Diclofenac sodium 0.1% was applied to the operative eyes five times a day for 5 days. The contralateral eyes served as controls. RESULTS: There was no significant between-group difference in sodium fluorescein concentrations in the 5 days after surgery. CONCLUSION: The findings underline our clinical impression that BAB disruption 5 days after surgery does not differ significantly with the type and length of scleral incision used for IOL implantation.

Blood-aqueous barrier in pseudoexfoliation syndrome: evaluation by immunohistochemical staining of endogenous albumin.

BACKGROUND: Alterations of the integrity of the blood-aqueous barrier (BAB) are frequent findings in eyes with pseudoexfoliation syndrome (PSX). METHODS: Immunohistochemical staining for the demonstration of albumin was used to analyze the BAB in 10 eyes with PSX without previous intraocular surgery and in 10 age-matched normal control eyes. RESULTS: In eyes with PSX, small amounts of albumin were detected along the anterior surface of the iris in 7, in the anterior chamber in 1, along the ciliary epithelium in 4, and in the trabecular meshwork in 9 of 10 eyes. PSX material was also immunoreactive. In the 10 normal control eyes, albumin was detected anterior to the iris stroma in 1 eye, in the anterior chamber in 2 eyes, in the trabecular meshwork in 1 eye, but not internal to the ciliary epithelium. CONCLUSIONS: Our findings indicate that impairment of the BAB in PSX can be localized at the level of the iris and, less frequently or to a lesser extent, at the level of the ciliary body.

Anterior chamber angle vascularization in Sturge-Weber syndrome. Report of a case.

The case of a 20-year-old woman with a left-sided facial hemangioma and a homolateral glaucoma is reported, complete with the histology of a trabeculectomy specimen. Her left eye had an episcleral hemangioma and goniodysgenetic features in the anterior chamber angle, while the intraocular pressure was measured to be 45 mmHg. The left optic disc showed a large cupping and the left visual field was constricted. The right eye had no glaucomatous changes. Histological examination of the trabeculectomy specimen by both light and electron microscopy showed multiple congenital anomalies. There was a cluster of blood vessels in the trabecular meshwork. Abnormal accumulations of fine granular extracellular matrixes were observed in both the juxtacanalicular connective tissue and around the vascular structures. The lumen of Schlemm's canal was subdivided into three or four parts with few giant vacuole structures. The endothelial cells lining the inner wall of Schlemm's canal contained a well-formed basal lamina with many villi projecting into the lumen. These findings suggest that the multiple anomalies observed in the trabecular tissue may contribute to the manifestation of glaucoma in Sturge-Weber syndrome.

[Effect of 0.1% dexamethasone and 1.0% prednisolone acetate eyedrops on the blood-aqueous humor barrier]. / Der Effekt von Dexamethason-0.1%- und Prednisolonazetat-1.0%-Augentropfen auf die Blut-Kammerwasser-Schranke.

In a randomized, double-blind clinical trial we studied the protective effect of prednisolone-acetate 1.0% and dexamethasone 0.1% on the blood-aqueous barrier after cataract-extraction and posterior chamber lens implantation. Pre- and postoperative anterior chamber fluorophotometry was performed after i.v. administration of 10% fluorescein-sodium in 20 eyes of 20 patients of whom 16 finished the study (mean age 68.7 +/- 11.0; 13 female, 3 male). The topical application of either drug 5 times daily for 5 days did show a significant difference in surgery mediated disturbance of BAB in each group before and after phacoemulsification. However, when comparing the effect of the two drugs with each other, a difference could not be detected (p = 0.35). To attain a statistical 95% probability that there is no significant difference between the two treatment groups, a number of 690 patients would have had to be investigated. The results can be interpreted as to be due to a better cornea penetration of prednisolone-acetate which compensate the higher glucocorticoid-potency and receptor-affinity of dexamethasone. The untreated fellow-eyes did not reveal a significant difference between the pre- and postoperative anterior chamber fluorescein-concentrations in either treatment group. Anterior chamber fluorophotometry is able to demonstrate the potency and influence of both prednisolone-acetate 1.0% and dexamethasone 0.1% eye-drops on the BAB following phacoemulsification and IOL-implantation. The difference of both drugs does not seem to be of clinical importance in this context.

Continued breakdown of the blood aqueous barrier following cataract surgery.

Following routine extracapsular cataract and posterior chamber implant surgery, recovery of the blood aqueous barrier (BAB) was quantified by sequential anterior chamber fluorophotometry. This was correlated with surgical details and postoperative findings to ascertain those factors which were related to excessive damage of the BAB immediately after surgery and to failure to recover a normal BAB by 3 months postoperatively. A cohort of 84 patients was followed. In the early postoperative period excessive levels of damage to the BAB were related to iris damage (p < 0.01) and diabetes mellitus (p < 0.01). By 3 months, 79% of the eyes had recovered normal BABs and 21% (18 eyes) had persisting excessive fluorescence which correlated with an abnormal pupil shape (p < 0.02) and the development of posterior synechiae (p < 0.001).

A model for testing the mutagenicity of excimer laser radiation in ophthalmology.

Because excimer laser radiation is applied more and more in therapeutic and refractive corneal surgery, the possibility of mutagenic side effects of this treatment should be considered. A mutagenicity model is presented approximating closely the ophthalmological conditions when mutagenic effects are studied: Heparinized human blood is filled into the anterior chamber of an enucleated cow eye. After irradiation of the cornea with the excimer laser, the blood is removed and whole blood cultures are set up. Lymphocytes are stimulated, fixed during metaphase, and scored for chromatid and chromosome aberrations. First results obtained with this model after 248 nm laser irradiation (500 J, 277 mJ/cm2, 10 or 20 Hz) revealed no mutagenic effects. However, when the blood was exposed under the same physical conditions in a quartz chamber (positive control), statistically highly significant increases of the yields of chromatid aberrations were observed.

Observation of blood-aqueous barrier function after posterior chamber intraocular lens implantation.

Fluorophotometry was performed on 306 eyes of 306 patients who had posterior chamber intraocular lens implantation after phacoemulsification or planned extracapsular cataract extraction procedures to compare the ratio of fluorescein concentration in the anterior chamber of operated eyes and of unoperated fellow eyes for age, postoperative period, and operative procedure. In this study, the breakdown and reestablishment of the blood-aqueous barrier after posterior chamber intraocular lens implantation was observed for a long period.

Comparison of the effects of argon and neodymium:YAG laser iridotomy on prostaglandin E2 and blood-aqueous barrier disruption.

We compared in rabbits the effects of laser iridotomy by either argon or neodymium (Nd):YAG laser on prostaglandin E2 (PGE2) production by the iris/ciliary body, its accumulation in the aqueous humor and the aqueous protein levels. PGE2 production by the iris/ciliary body, following exposure to argon or Nd:YAG laser, was similarly enhanced, with peak levels of 22.8 +/- 4.7 and 24.1 +/- 8.2 ng/mg, respectively. An increase in aqueous PGE2 levels was more pronounced in the argon as compared with the Nd:YAG group, with peak levels of 56.7 +/- 17.3 and 20.0 +/- 7.7 ng/ml, respectively. PGE2 production correlated well with aqueous PGE2 levels in the argon group, but not in the Nd:YAG group. Protein accumulated in the aqueous humor following irradiation by both types of laser light, with higher levels occurring in the argon group. These results are indicative of possible differences in the extent of the inflammatory reaction induced by the application of argon and Nd:YAG laser light to the iris.