A prospective study on intravitreal bevacizumab (Avastin) for neovascular age-related macular degeneration of different durations.

PURPOSE: Choroidal neovascularization (CNV) accounts for 85-90% of severe visual impairment in age-related macular degeneration (AMD). Vascular endothelial growth factor (VEGF) is a major factor mediating angiogenesis, and VEGF inhibitors have become a new treatment modality. In this prospective study, we used bevacizumab (Avastin), a recombinant monoclonal antibody to VEGF, to treat neovascular AMD. METHODS: The case material comprised 36 subjects (26 females, 10 males) aged 65-88 years with subfoveal neovascular AMD with all subtypes of CNV. There were two categories of patients: category I, long-standing CNV (12 months or more), preoperative visual acuity (VA) 0.16 (mean); category II, CNV (duration < 12 months), preoperative VA 0.25 (mean). Evaluation protocol included the Early Treatment Diabetic Retinopathy Study (ETDRS) VA, clinical ophthalmological examination, fluorescein angiography and optical coherence tomography (OCT). Intravitreal injections of bevacizumab (Avastin) (IVB), 1.25 mg (0.05 ml), were given under an operating microscope and aseptic conditions in a theatre for surgery with intervals of 4 or 6 weeks during the first 3 months and subsequently according to clinical assessment. The follow-up was 6 months in all cases. RESULTS: At 6 months, mean VA had improved by 4.6 ETDRS letters in the entire case material (P = 0.001), by 3.9 letters in category I (duration 12 months or more) and by 6.0 letters in category II (duration < 12 months). A total of 148 IVB (mean 4.1 injections/eye) were delivered during 6 months, the first 3 months comprising 3.1 IVB (mean) and the last 3 months 1.0 IVB (mean). No eyes suffered visual decline of 15 ETDRS letters. Fluorescein angiograms displayed stabilization or regression of CNV activity; OCT showed resorption of intraretinal oedema and subretinal fluid. No severe complications occurred but recurrence was common, and repeated IVBs were necessary in most cases during the 6-month period. CONCLUSION: When addressing the issue of frequency of IBV, we observed that 6-week intervals were sufficient because VA and CNV lesions generally stabilized at 4 weeks. The gain in VA was promising in eyes with < 12 months CNV duration. Even in eyes with a longer CNV duration, a slight visual improvement was observed when retinal oedema resorbed, although subretinal fibrosis and general cellular damage certainly limited recovery.

Preoperative sub-Tenon's capsule injection of ropivacaine in conjunction with general anesthesia in retinal detachment surgery.

OBJECTIVE: To evaluate the effects of preoperative sub-Tenon's capsule injection of ropivacaine on intraoperative hemodynamics, postoperative pain, nausea, and recovery in patients undergoing scleral buckling surgery under general anesthesia (GA). DESIGN: Randomized double-masked controlled clinical trial. PARTICIPANTS: Ninety-eight patients with primary rhegmatogenous retinal detachment undergoing scleral buckling surgery under GA. METHODS: Random allocation to either preoperative sub-Tenon's capsule injection of 3 ml of 0.75% ropivacaine or sub-Tenon's capsule injection of 3 ml of saline (controls) immediately before a scleral buckling procedure under GA. Intraoperative monitoring of hemodynamic parameters, need of analgesia with sevoflurane and alfentanil, time in the recovery unit, measurements of pain and nausea on the visual analog scale (VAS) up to 12 hours postoperatively, and consumption of analgesics and antiemetics was recorded. MAIN OUTCOME MEASURES: Intraoperative systolic blood pressure (BP); bradycardia; minimum alveolar concentration (MAC) of sevoflurane; maximum postoperative VAS scores of pain and nausea; time in recovery unit; and total need of alfentanil, ketobemidone, dextropropoxyphene, and dixyrazine. RESULTS: Ninety-seven patients were analyzed (48 in the ropivacaine group and 49 controls). A significantly lower intraoperative systolic BP (104+/-6 vs. 112+/-7 mmHg; P = 0.004), less need of sevoflurane (1.33+/-0.19 vs. 1.56+/-0.23; P = 0.03), and shorter time in the recovery unit (67+/-9 vs. 76+/-16 minutes; P = 0.01) were observed in the ropivacaine group. Maximum VAS pain scores were 50+/-21 in the control group and 36+/-25 in the ropivacaine group (P = 0.05), with a significantly lower consumption of opioids (ketobemidone) in the ropivacaine group (3.6+/-3.5 vs. 1.3+/-2.0 mg). No significant difference was observed regarding nausea or need of dixyrazine or dextropropoxyphene postoperatively. CONCLUSIONS: Preoperative sub-Tenon's capsule injection of ropivacaine in scleral buckling surgery under GA lowers the intraoperative systolic BP, reduces the amount of inhalable sevoflurane needed, and enhances postoperative vigilance through reduction of pain and need of opioids.

Delayed inflammation-associated corneal neovascularization in MMP-2-deficient mice.

Corneal neovascularization is a significant, sight-threatening, complication of many ocular surface disorders, but its underlying molecular background is still not fully understood. In the present study, we analysed the expression and role of matrix metalloproteinase-2 (MMP-2), a proteolytic enzyme suggested to regulate angiogenesis, in a mouse model of inflammation-related corneal neovascularization. A silk suture was placed centrally in pigmented mice corneas causing limbal vasculature to sprout, forming new vessels. Neovascularization progressed centrally involving the entire cornea after about 12 days. Histological analysis revealed vascularization of the corneal stroma accompanied by a marked inflammatory response. The neovascularization correlated with an increased expression of MMP-2 mRNA and protein that was mainly found in cells that stained positively for S100A4, a marker for activated keratocytes. MMP-2-deficient mice and wild-type mice were compared in a kinetic study, showing a statistically significant delay of neovascularization in MMP-2-deficient mice. These results implicate a role for MMP-2 in experimental inflammation-associated corneal neovascularization.

TIMP-3 mRNA is not overexpressed in Sorsby fundus dystrophy.

PURPOSE: To assess the expression of MMP (matrix metalloproteinase)-2 and -9 and TIMP (tissue inhibitors of metalloproteinases)-1, -2, and -3 in Sorsby fundus dystrophy. DESIGN: Cliniciopathological report. METHODS: A donor eye with a confirmed S181C mutation in the TIMP-3 gene and an age-matched normal donor eye were studied using in situ hybridization technique with MMP -2 and -9 and TIMP -1, -2, and -3 probes. RESULTS: There is a reduction of mRNA expression of MMP-2 and TIMP-3 in the Sorsby retinal pigment epithelium cells. CONCLUSIONS: Increased expression of TIMP-3 mRNA does not cause accumulation of TIMP-3 in the Bruch membrane of Sorsby fundus dystrophy nor is it likely to cause age-related macular degeneration.

Reduced choroidal neovascular membrane formation in matrix metalloproteinase-2-deficient mice.

PURPOSE: Findings in studies have suggested a role for matrix metalloproteinase (MMP)-2 in angiogenesis, including choroidal neovascularization (CNV). To investigate further, the current study was conducted to observe the formation of experimental CNV in MMP-2-deficient mice. METHODS: CNV was induced in wild-type and MMP-2-deficient mice by krypton laser photocoagulation of the fundus. The time-course of expression of MMP-2 mRNA after laser treatment was determined by in situ hybridization with anti-sense and sense cRNA probes. MMP-2 protein distribution was determined by immunohistochemistry. Ten days after treatment, the extent of CNV was evaluated on hematoxylin-eosin stained serial sections. The maximum height of the CNV lesions was calculated by image analysis of digitized histologic images. RESULTS: Expression of MMP-2 mRNA was detected in the CNV lesions at day 3 after laser treatment and peaked at day 5, after which it slowly declined. MMP-2 mRNA expression appeared to be highest at the margins of the membrane. Immunostaining for MMP-2 confirmed the presence of MMP-2 protein in the CNV lesions. The CNV lesions of MMP-2-deficient mice showed that relative thickness was reduced by 31% compared with wild-type mice (P = 0.006). CONCLUSIONS: The present study demonstrated that MMP-2 mRNA and protein are upregulated during experimental CNV in the mouse. The marked difference in thickness of the CNV membrane between wild-type and MMP-2-deficient mice shows that MMP-2 is involved in the formation of experimental CNV in the mouse. These results suggest that pharmacologic targeting of MMPs, including MMP-2, may reduce formation of CNV in conditions such as age-related macular degeneration.

Photodynamic therapy for circumscribed choroidal haemangioma.

PURPOSE: To assess the efficacy of photodynamic therapy (PDT) as a new treatment for circumscribed choroidal haemangioma (CCH). METHODS: Eight patients with CCH were treated with PDT using a protocol similar to that used in the standard treatment of neovascular age-related macular degeneration. RESULTS: Visual acuity improved in six of eight eyes, remained unchanged in one eye and deteriorated in one eye after 3-15 months (median 7 months) follow-up. Pre-treatment metamorphopsia disappeared in all but two cases. The thickness of the CCH measured with standardized echography showed marked regression within 1 month after PDT. In six eyes there was no remaining protrusion after PDT and one lesion was barely detectable. One patient experienced a transient choroidal effusion and perifoveal haemorrhage. CONCLUSION: Photodynamic therapy is a promising new treatment for CCH as it restores visual function in most cases without causing apparent ocular or systemic side-effects.