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UBM-guided chamber angle surgery for glaucoma management: an experimental study.

PURPOSE: The aim of this experimental study was to investigate the potential of ultrasound bimicroscopy (UBM)-guided chamber angle surgery as an alternative or supplement to gonioscopy and intraocular microendoscopy for intraoperative control. METHODS: In 15 porcine cadaver eyes, mechanical goniopuncture or punctual Er:YAG laser trabecular ablation was performed without operating microscope or gonioscopy, but with real-life ultrasound biomicroscopy monitoring with a 50 MHz transducer. Intraoperative localization of the microsurgical instruments and tissue-instrument contact were qualitatively evaluated. RESULTS: The instruments could be clearly visualized within the chamber angle and disturbing artefacts were only minimal when using mechanically fixed instruments in slow motion. Topographic localization, tissue contact, and penetration depth of the instruments entering the scleral were well illustrated as far as the technical resolution limits of UBM would allow. CONCLUSIONS: UBM can be used intraoperatively to monitor the correct manoeuvring of microsurgical instruments in selected ab interno procedures. Some adaptations and further modifications of the technique presented here will be necessary before UBM-guided surgery can be considered for clinical use in humans.

Animals↗

In vitro and in vivo evaluation of an ocular delivery system of 5-fluorouracil microspheres.

Solvent evaporation technique with O/O (oil/oil) emulsion was used to prepare 5-FU (5-fluorouracil) biodegradable microspheres with a polymer of poly(dl-lactide-co-glycolide) combining lecithin as an emulsifier. In vitro drug release was conducted in phosphate buffer with pH 7.4 at 37 degrees C. For in vivo studies, 10 mg of 5-FU microspheres (containing 1 mg of 5-FU) were implanted in the conjunctival area of the rabbit eye. Rabbits were sacrificed at certain time intervals within 7 days after drug application. Samples of aqueous humor and sclera were prepared and analyzed by the high performance liquid chromatography (HPLC) method. The tested 5-FU microsphere contained 10% drug with a mean particle size of 4.4 +/- 0.6 microm. The microsphere had a burst release initially (64.9 +/- 1.5%), followed by a sustained release; the cumulative release at time points of 1, 10 and 21 days were 71.9 +/- 1.9%, 80.1 +/- 2.1% and 89.8 +/- 2.3%, respectively. For in vivo studies, aqueous humor levels showed a peak at the first sampling point (2 hr), then maintained low levels of 5-FU with a range 0.2-1 microg/mL. Scleral levels were 20-80 microg/mL during a 7-day study. Our results indicate that the prepared 5-FU microsphere provided a long-term release for more than 1 week. The preparation showed no irritation and low toxicity (< 100 microg/mL). For application to the eye, it might be potentially useful as a complement drug system in glaucoma filtration surgery.

Animals↗

Human anti-transforming growth factor-beta2 antibody: a new glaucoma anti-scarring agent.

PURPOSE: Currently available anti-scarring regimens for glaucoma filtration surgery have potentially blinding complications and thus the need for alternative and safer agents. The effects of a new antibody to transforming growth factor (TGF)-beta2 on in vitro and in vivo conjunctival scarring and after glaucoma filtration surgery were investigated. METHODS: The activity of a novel recombinant monoclonal neutralizing antibody (mAb) to human TGF-2 (rhAnti-TGF-beta2 mAb) was studied in conjunctival fibroblast-mediated proliferation, migration, and collagen contraction. Its safety in subconjunctival administration was assessed in vivo, and, in a rabbit model of glaucoma filtration surgery, its effects on conjunctival scarring and filtration surgery outcome were investigated. RESULTS: The rhAnti-TGF-beta2 mAb effectively inhibited TGF-beta2-mediated conjunctival scarring activity in vitro, at 50% inhibitory concentrations (IC50) of less than 1 nM. It significantly improved glaucoma filtration surgery outcome in an animal model of aggressive conjunctival scarring compared with control (P = 0.0291) and was clinically safe, nontoxic, and well tolerated after subconjunctival administration. CONCLUSIONS: Subconjunctival rhAnti-TGF-beta2 mAb treatment significantly affects surgical outcome and effectively reduces conjunctival scarring both in vitro and in vivo. It appears safe for subconjunctival administration and when compared with mitomycin-C treatment histologically, much less destructive to local tissue. rhAnti-TGF-beta2 mAb may have potential as a new anti-scarring agent for use in glaucoma filtration surgery.

Animals↗

[Clinical observation of combined surgery for cataract and glaucoma: phacoemulsification and viscocanalostomy].

OBJECTIVE: To evaluate the therapeutic effects and safety of phacoemulsification-intraocular lens (IOL) implantation combined with viscocanalostomy (V-P) and compared the outcomes of phacoemulsification-IOL implantation combined with trabeculectomy (T-P). METHODS: Combined phacoemulsification with corneal incision, foldable intraocular lens implantation and viscocanalostomy was performed in 30 eyes of 28 cataract patients with primary open-angle glaucoma. RESULTS: Follow-up was performed up to 6 months after surgery. The mean intraocular pressure (IOP) of V-P group was (14.65 +/- 2.70) mm Hg (1 mm Hg = 0.133 kPa) with a mean pressure reduction of 10.33 mm Hg compared with IOP before the operation (P = 0.000). There were no statistical differences of the IOP within two groups during postoperative 1 week, 1 and 6 month (P = 0.661, 0.381, 0.526). Postoperatively, the best corrected visual acuities of V-P group were > or = 0.5 in 18 eyes (follow-up 29 eyes, 62.1%), 20 eyes (28 eyes, 71.4%), 24 eyes (30 eyes, 80.0%) at 1 week, 1 month and 6 months, but no statistical difference with T-P group, (P = 0.621, 0.702, 0.893). Complications of V-P group included: Descemet's membrane puncture 2 eyes (6.7%), Schlemm's tube puncture 2 eyes (6.7%) and IOP spikes 4 eyes (13.3% at 24 hours postoperatively). The V-P group showed a significantly less inflammation, hyphema and choroidal detachment than that in the T-P group. CONCLUSIONS: Phacoemulsification-IOL implantation combined with viscocanalostomy is a safe and efficacious surgery with lower complications.

Adult↗

Secondary glaucoma after congenital cataract surgery.

PURPOSE: Glaucoma has been recognized as an infrequent but serious complication following surgery for congenital cataract in childhood. We conducted a retrospective review of patients in whom glaucoma had developed after surgery for congenital cataract. METHODS: We reviewed the records of 87 eyes of 53 patients on whom cataract surgery had been performed between February 1982 and March 1995 at Ondokuz Mayis University Hospital, Samsun. RESULTS: The average postoperative follow-up is 4.5 years (range 1 to 12 years). We identified open angle glaucoma (OAG) in 17 eyes, chronic angle closure glaucoma (ACG) in six eyes, and acute angle closure glaucoma (AACG) in two eyes. The average time between cataract surgery and the diagnosis of glaucoma was 6.08 years (range one week to 10 years). The mean time to diagnosis of glaucoma was 4.7 years (range 4 months to 10 years) for OAG, 4.3 years (range 1 to 8 years) for ACG and, for AACG, 7 days and 10 months following surgery. Medication alone was successful in intraocular pressure control in 17 of 25 eyes (<21 mmHg), and additional surgical procedures resulted in intraocular pressure control in eight eyes in which they were performed. CONCLUSION: Patients undergoing cataract surgery early in life should be routinely examined for possible postoperative glaucoma.

Cataract↗

Evaluation of anti-TGF-beta2 antibody as a new postoperative anti-scarring agent in glaucoma surgery.

PURPOSE: Postoperative subconjunctival wound healing remains the commonest cause of late bleb failure after glaucoma filtration surgery. This study was undertaken to investigate whether the human monoclonal antibody that neutralizes transforming growth factor-beta2 (CAT-152; lerdelimumab) could be used as a postoperative agent to prevent scarring after glaucoma surgery and compared it with 5-fluorouracil (5-FU), to benchmark its potential clinical benefit. METHODS: In a randomized, controlled, masked-observer study, after modified glaucoma surgery, 48 rabbits were randomly allocated to receive a postoperative course of seven subconjunctival injections of CAT-152 (1 mg/mL), 5-FU (50 mg/mL), or no treatment. Bleb characteristics, the presence of subconjunctival drainage, and local reaction to treatment were assessed. Animals were killed on days 10, 21, and 30. Immunohistochemistry, histologic staining and electron microscopy were performed to demonstrate the mechanism of CAT-152-mediated effects on the extracellular matrix. RESULTS: CAT-152 significantly improved surgical outcome (log rank test, P < 0.001) and reduced subconjunctival collagen deposition (P < 0.01) compared with 5-FU and control. Median bleb survival was increased in the CAT-152 group (23.5 days) compared with the 5-FU (20 days) and control (16 days) treatment groups. CAT-152 treatment improved bleb morphology (P < 0.05) and was well tolerated. 5-FU prolonged the duration of corneal epitheliopathy (P < 0.01). CONCLUSIONS: Postoperative administration of CAT-152 significantly improved surgical outcome, reduced subconjunctival scarring, and minimized the risk of corneal side effects compared with the anti-scarring agent 5-FU. These findings suggest that CAT-152 may offer therapeutic benefit as a postoperative agent to prevent subconjunctival scarring after glaucoma filtration surgery.

Animals↗

Intracorneal hematoma with descemet membrane detachment after viscocanalostomy.

PURPOSE: To describe a case of intracorneal hematoma with Descemet membrane detachment after viscocanalostomy. DESIGN: Interventional case report. METHODS: A 63-year-old with uncontrolled primary open-angle glaucoma underwent viscocanalostomy. During the introduction of hyaluronate 2.3% under the superficial flap, a limited lysis of Descemet membrane was observed. RESULT: Slit-lamp biomicroscopy showed an intracorneal hematoma with Descemet membrane detachment 1 day after viscocanalostomy. The creation of an intentional break of Descemet membrane and descemetopexy using sulfur hexafluoride gas were performed. The cornea regained transparency after surgery. CONCLUSIONS: Intracorneal hematoma with Descemet membrane detachment is a possible complication of viscocanalostomy.

Anterior Chamber↗

Efficacy and safety of bimatoprost in patients with uncontrolled glaucoma as alternative to filtration surgery.

PURPOSE: To evaluate the efficacy and safety of bimatoprost 0.03% as an alternative to filtration surgery in patients with uncontrolled glaucoma. DESIGN: Interventional study. METHODS: A total of 83 consecutive patients (83 eyes) awaiting glaucoma surgery were enrolled in eight ophthalmic centers. Reasons for listing were inadequate intraocular pressure (IOP) control despite medical therapy and documented progression of visual field loss. All patients discontinued the previous treatment and were switched to bimatoprost 0.03% QD (one drop at 9 pm). The primary efficacy outcome was a 20% IOP reduction from baseline at each timepoint. IOP was measured at day 7, day 30, day 60, and day 90 of treatment; less than 20% IOP reduction was considered as a failure. RESULTS: An IOP reduction of at least 20% was achieved in 74 patients (89.1%) after 7 days and in 64 patients (86.5%) after 30 days. Sixty-two patients (74.6%) maintained IOP readings 20% lower than baseline after 60 and 90 days. In these patients, visual field indices improved in 8 eyes (13%), and remained unchanged in 54 eyes (87%). Ocular side effects were conjunctival injection (15.6%), burning sensation (9.6%), foreign body sensation (4.8%), and eyelash growth (2.4%). CONCLUSIONS: This preliminary study shows that bimatoprost 0.03% could represent a useful therapeutic tool that might defer filtration surgery.

Aged↗

[Application of mitomycin C in glaucoma filtration surgery].

OBJECTIVE: To investigate the efficacy and the complication of glaucoma filtration surgery with intraoperative mitomycin C. METHODS: Between April 1994 and February 1996, 33 eyes of 28 patients underwent filtration procedures with intraoperative mitomycin C. Then a follow up of mean 6.65 months (range, 1-12 months) was taken. RESULTS: The Class I success rate was 72.7% when the intraocular pressure (IOP) was less or equal to 2.79 kPa without glaucoma medicine. The Class II success rate was 24.2% when the IOP was controlled with topical glaucoma medicine. In the postoperative period, persistant hypotony developed in 4 eyes, and hypotony-related maculopathy developed in 2 of these eyes. No conjunctival wound leak and endophthalmitis was present. CONCLUSIONS: Intraoperative mitomycin C in glaucoma filtration surgery can increase the success rate, while it is associated with a higher incidence of complications such as hypotony.

Adolescent↗

Randomized clinical trial of the influence of local water-filtered infrared A irradiation on wound healing after abdominal surgery.

BACKGROUND: Postoperative local water-filtered infrared A (wIRA) irradiation improves tissue oxygen partial pressure, tissue perfusion and tissue temperature, which are important in wound healing. METHODS: The effect of wIRA irradiation on abdominal wound healing following elective gastrointestinal surgery was evaluated. Some 111 patients undergoing moderate to major abdominal surgery were randomized into one of two groups: wIRA and visible light irradiation (wIRA group) or visible light irradiation alone (control group). Uncovered wounds were irradiated twice a day for 20 min from days 2-10 after operation. RESULTS: Irradiation with wIRA improved postoperative wound healing in comparison to visible light irradiation alone. Main variables of interest were: wound healing assessed on a visual analogue scale (VAS) by the surgeon (median 88.6 versus 78.5 respectively; P < 0.001) or patient (median 85.8 versus 81.0; P = 0.040), postoperative pain (median decrease in VAS score during irradiation 13.4 versus 0; P < 0.001), subcutaneous oxygen tension after irradiation (median 41.6 versus 30.2 mmHg; P < 0.001) and subcutaneous temperature after irradiation (median 38.9 versus 36.4 degrees C; P < 0.001). The overall result, in terms of wound healing, pain and cosmesis, measured on a VAS by the surgeon (median 79.0 versus 46.8; P < 0.001) or patient (79.0 versus 50.2; P < 0.001) was better after wIRA irradiation. CONCLUSION: Postoperative irradiation with wIRA can improve normal postoperative wound healing and may reduce costs in gastrointestinal surgery.

Aged↗

[Combined surgery for cataract and glaucoma: phacoemulsification, foldable intraocular lens implantation and viscocanalostomy].

OBJECTIVE: To assess the outcome of phacoemulsification-intraocular lens (IOL) implantation combined with viscocanalostomy (P-C group), compared with that of phacoemulsification-IOL implantation combined with trabeculectomy (P-T group). METHODS: Combined phacoemulsification with corneal incision, foldable intraocular lens implantation and viscocanalostomy was performed in 21 eyes of 19 cataract patients with primary open-angle glaucoma. All patients were followed up for 3 - 6 months. RESULT: Intraocular pressure (IOP) was significantly lower in both P-C group and P-T group (P=0.000). There was no statistically significant difference between two groups. Visual outcome was similar in both groups. Complications of P-C group included Descemet's membrane puncture in 2 eyes, Schlemm's tube puncture in 2 eyes and IOP spikes in 3 eyes (at 24 hours postoperatively). The P-C group experienced significantly less inflammation than the P-T group. CONCLUSION: Phacoemulsification-IOL implantation combined with viscocanalostomy is a safe and effective surgery, with lower complicatin rate and easier ambulatory care.

Aged↗

T-Flux implant versus Healon GV in deep sclerectomy.

PURPOSE: To compare the efficacy and safety of T-Flux implant versus Healon GV in deep sclerectomy. METHODS: Randomized prospective trial of 23 eyes of 20 patients with medically uncontrolled open angle glaucoma over a period of 24 months, who underwent deep sclerectomy with either Healon GV or T-Flux implant. RESULTS: Mean postoperative intraocular pressure was 13.2 +/- 3.0 mm Hg with T-Flux implant (group 1) and 12.2 +/- 3.5 mm Hg with Healon GV (group 2), with a pressure reduction of 53.0% in group 1 (13.2 mm Hg vs. 28.1 mm Hg) and of 48.1% in group 2 (12.2 mm Hg vs. 23.5 mm Hg). Qualified and complete successes were 100% and 95.4% respectively. Pressures equal to or less than 15 mm Hg were 81.8% in group 1 and 90.9% in group 2 with or without treatment, and 63.6% in group 1 and 81.8% in group 2 without treatment. The number of glaucoma treatments dropped from 2.5 +/- 0.9 to 0.4 +/- 0.7 in group 1 and from 2.2 +/- 1.0 to 0.2 +/- 0.4 in group 2. The goniopuncture rate was 63.6% in group 1 and 36.4% in group 2, with a mean pressure drop of 6.1 +/- 3.9 mm Hg and 3.25 +/- 1.2 mm Hg respectively. Overall, slit-lamp diagnosed surgery-related complications included positive Seidel (13.6%), hyphaema (22.7%), choroidal detachment, and iris incarceration (4.5% each). At 2 years, ultrasound biomicroscopy showed mainly low reflective (40.1%) and flattened (36.4%) blebs. Principally latter ones were associated with the need for adjunctive treatment. A hypoechoic area in the suprachoroidal space was seen in at least 59.1% of eyes at 2 years and was not associated with lower intraocular pressure. CONCLUSION: Deep sclerectomy is an effective and safe surgery. However, longer follow up and larger study groups are required to assess the additional benefit of nonabsorbable implants.

Aged↗

Glaucoma: early detection and therapy for prevention of vision loss.

Glaucoma is the second most common cause of permanent blindness in the United States and the most common cause of blindness among blacks. It is characterized by optic atrophy and vision loss, resulting from intraocular pressure that is too high to allow normal function of the optic nerve. Examination of the optic nerve and assessment of individual risk factors aids in the identification of patients who are at risk for glaucoma. Although glaucoma is a chronic disease, ocular complications can be prevented and sight may be preserved if the disease is detected early. A combination of antiglaucoma medications, laser treatment and filtration surgery is used to maintain intraocular pressure at a level sufficient to halt progression of optic nerve injury and prevent further vision loss.

Adrenergic beta-Agonists↗

Surgical management of patients with combined glaucoma and corneal transplant surgery.

The reasons for having combined glaucoma and corneal transplant surgery are myriad. Patients with corneal transplants have a high frequency of developing secondary glaucoma. Patients with preexisting glaucoma have even higher risk for developing glaucoma refractory to medical management after penetrating keratoplasty. The indication for corneal transplant affects the risk for developing postkeratoplasty glaucoma. The surgical treatment options for treating glaucoma include laser trabeculoplasty, cycloablation, trabeculectomy, and glaucoma drainage implants. In addition, the sequencing of glaucoma surgery relative to penetrating keratoplasty affects the outcome. Newer corneal transplant techniques may have a lower risk for developing secondary glaucoma.

Ciliary Body↗

In vitro sensitivity of human Tenon's capsule fibroblasts to mitomycin C and its correlation with outcome of glaucoma filtration surgery.

Dose-inhibition studies of proliferating fibroblasts grown from Tenon's capsule biopsy specimens obtained during trabeculectomy from 17 glaucoma patients were performed using varying concentrations of mitomycin C (MMC), with exposure of cells to the drug for either 5 days or 5 minutes. Surgical outcomes were determined 3 months postoperatively. Based on in vitro results, fibroblasts were classified as either MMC-"resistant" or MMC-"sensitive." Thirteen surgically successful cases were associated with 10 "sensitive" and three "resistant" fibroblasts; four surgical failures with one "sensitive" and three "resistant" fibroblasts. The in vitro studies were positively correlated with the clinical outcomes, the former correctly predicting the latter in 76.5% of the surgeries.

Adolescent↗

Effect of varying the mitomycin-C treatment area in glaucoma filtration surgery in the rabbit.

PURPOSE: To investigate the effect of varying the treatment area of subconjunctival mitomycin-C (MMC) using an adapted rabbit model of filtration surgery. METHODS: Twenty-four New Zealand White rabbits underwent filtration surgery, with random allocation to one of three treatments: 5-minute subconjunctival applications of MMC (0.4 mg/ml) with either a large (8 x 10 mm) or small (4 x 2 mm) sponge or no treatment (control). Drainage was achieved by placing an intravenous cannula through a scleral tunnel into the anterior chamber. Rabbits were examined at set intervals for up to 30 days after surgery. Measurements of appearance, size, height, and vascularity of blebs and of intraocular pressure and anterior chamber depth were made by a masked observer. Histologic analysis of eyes was performed at 3, 14, and 30 days. RESULTS: Statistical analysis showed a significant difference in bleb survival among all groups (log rank P = 0.0054, with 100% survival with large areas of MMC treatment). Comparison between large and small treatment area groups revealed significant differences in bleb survival (log rank P = 0.0388); bleb area (between-subject analysis, P = 0.009), and bleb height (between-subject analysis, P = 0.005). These differences were seen clinically, with large areas of MMC treatment producing diffuse and elevated blebs, small areas of treatment producing thin-walled and localized blebs with scarring at 21 days, and no treatment resulting in comparatively vascularized and scarred blebs before 14 days. Histologic analysis revealed clear differences among groups, with an increase in subconjunctival cellularity and scar tissue in eyes with failed blebs. CONCLUSIONS: The size of the area of subconjunctival MMC treatment significantly affects surgical outcome. Histologic features mirror differences observed clinically. Alteration of the size of the MMC treatment area may provide an alternative and more controllable approach to modulating the wound-healing response after drainage surgery and, more important in the clinical context, to modifying bleb morphology.

Animals↗

[Complications following Molteno implant surgery: case report].

We present a 43-year old patient with refractory secondary glaucoma, who showed epithelial downgrowth into the anterior chamber following Molteno implant surgery. It will be discussed, whether the Molteno implant or the following keratoplasty, which was necessary because of corneal decompensation, caused the epithelial downgrowth.

Adult↗

Adenoviral p53 gene transfer inhibits human Tenon's capsule fibroblast proliferation.

BACKGROUND/AIM: Although antiproliferative drugs have been used successfully to prevent scarring after filtration surgery in patients with glaucoma, complications associated with their use (such as hypotony or endophthalmitis) energise the search for an alternative treatment. Single application of beta radiation leads to long term growth arrest and expression of p53 in human Tenon's capsule fibroblasts (hTf). The authors assume that the activation of p53 is one of the cellular triggers. Their aim was to analyse the effect of p53 overexpression on hTf and to determine which pathways are involved. METHODS: A recombinant adenoviral vector (rAd.p53) containing transgenes encoding for human p53 and green fluorescent protein (GFP) was used to induce overexpression of p53 in hTF and a control vector (rAd.GFP). Transgene expression was detected by western blot (p53 and p21WAF-1/Cip1). Cell proliferation and viability were investigated using cell counts, 5'-bromodeoxyuridine incorporation (BrdU assay) and tetrazolium reduction (MTT assay). RESULTS: Infection of hTf with rAd.p53 resulted in significant inhibition of cell proliferation, DNA synthesis, and metabolic activity in vitro. Western blot showed increased levels of p53 and p21WAF-1/Cip1 in rAd.p53 infected cells, but not in rAd.GFP and uninfected cells. Apoptosis was excluded with flow cytometry. CONCLUSIONS: Adenoviral p53 gene transfer leads to significant growth inhibition in hTf. P53 induces p21(WAF-1/Cip1) expression and does not cause apoptosis in hTf in vitro. p53 as an antiproliferative drug has the potential to replace mitomycin C and 5-fluorouracil in glaucoma surgery.

Adenoviridae↗