Toxicity of subretinal ribozyme to the proliferating cell nuclear antigen and 5-fluorouracil in rat eyes

PURPOSE: To investigate the subretinal toxicity profile of the ribozyme to the proliferating cell nuclear antigen (PCNA-Rz) and 5-fluorouracil (5-FU), as well as the highest nontoxic subretinal dose of the mixture of the two agents in rat eyes. METHODS: Brown-Norway rats received subretinal injections of 1 microg, 10 microg, and 100 microg/microl PCNA-Rz and 0.06 microg/microl, 0.3 microg/microl, and 1.5 microg/microl 5-FU in the right eyes, and the left eyes were injected with H-BSS as control. Each dose was tested on 5 eyes in a 5 microl volume. In a second study, a combination of 5-FU (1.5 microg/microL) with varying 10-30-50 microg/microl doses of PCNA-Rz was tested in a regimen of four sequential subretinal injections. Toxicity was monitored by biomicroscopy, indirect ophthalmoscopy, electroretinography (ERG), and histology. RESULTS: The highest nontoxic dose for subretinal PCNA-Rz was 10 microg/microl, whereas 100 microg/microl showed disturbance of pigmentation with corresponding histological changes of retinal photoreceptor loss and retinal pigment epithelium proliferation or irregularities. Subretinal injection of all three doses of 5-FU did not show any toxicity. Serial injections of a mixture of 1.5 microg/microl 5-FU with 10 microg/microl of PCNA-Rz was found to be safe in rat eyes. CONCLUSIONS: Subretinal injections of the combination of PCNA-Rz (10 microg/microl) and 5-FU (1.5 microg/microl) demonstrated to be safe in rat eyes during the course of this study, even with a multiple administration of four injections.     

Inhibition of laser-induced choroidal neovascularization by atorvastatin by downregulation of monocyte chemotactic protein-1 synthesis in mice

PURPOSE: To determine the effect of atorvastatin, an HMG CoA reductase inhibitor, on experimental choroidal neovascularization (CNV) induced by laser photocoagulation in mice. METHODS: CNV was induced by laser photocoagulation in normal wild-type mice. The mice received either oral atorvastatin 10 (AS10 group) or 20 (AS20 group) mg/kg per day 3 days before and after laser application; 1 (AS1) and 2 (AS2) mg/kg per day were included in the measurement of the parameters of CNV volume and the expression of chemoattractant CC chemokine ligand 2/monocyte chemoattractant protein-1 (CCL2/MCP-1) and intracellular adhesion molecule (ICAM)-1. CNV responses were compared based on volume measurements 2 weeks after laser photocoagulation. Expression of vascular endothelial growth factor (VEGF), CCL2/MCP-1, and ICAM-1 in the RPE and choroid was quantified by ELISA 2 or 3 days after photocoagulation. Macrophage infiltration of the choroid was determined by flow cytometry. RESULTS: The mean CNV volume was significantly smaller in the AS1 (44.16 +/- 4.67 x 10(4) microm(3)), AS2 (36.49 +/- 4.64 x 10(4) microm(3)), AS10 (25.75 +/- 2.41 x 10(4) microm(3)), and AS20 (33.24 +/- 8.42 x 10(4) microm(3)) groups compared with control mice (64.21 +/- 2.27 x 10(4) microm(3); P = 0.0004, P < 0.0001, P < 0.0001, P < 0.0001, respectively). The mean VEGF and CCL2/MCP-1 protein levels decreased significantly (P = 0.001, P = 0.02, respectively) in the treated group compared with the control group. ICAM-1 expression did not differ significantly between the treated and control groups. The number of choroid-infiltrating macrophages decreased markedly in the treated group. CONCLUSIONS: Atorvastatin effectively inhibited laser-induced CNV in mice and was associated with downregulation of CCL2/MCP-1 and VEGF and reduced macrophage infiltration into the RPE/choroid.     

Evaluation of subretinal triamcinolone acetonide in patients with exudative age-related macular degeneration.

PURPOSE: The aim of this paper was to present the results of subretinal delivery of triamcinolone acetonide (TCA) in humans with choroidal neovascularization (CNV) caused by age-related macular degeneration (AMD). METHODS: Twenty two (22) eyes of 22 patients underwent pars plana vitrectomy with subretinal TCA administration. Two milligrams (2 mg) of preservative-free TCA were delivered through a 32-gauge automatic subretinal injector in 20 microL of volume. Visual acuity, fluorescein angiography (FA), and intraocular pressure (IOP) were recorded and compared pre- and postoperatively. RESULTS: Preoperative average+/-standard deviation visual acuity in the treated eye was 1.408+/-0.129 (logMAR; median 20/400) and 1.403+/-0.114 (logMAR; median 20/300) postoperatively (P=0.51). The mean area of pre- and postoperative FA leakage in the operated eyes was 21.31+/-1.125 and 19.29+/-1.108 mm2, respectively (P=0.04). The average IOP value before treatment was 15.3+/-0.78 mmHg. Three (3) months after surgery, it was 20.5+/-2.04 mmHg (P=0.02). Six (6) months and 1 year after surgery, the average IOP was 17.0+/-0.66 mmHg (P=0.9) and 15.6+/-1.02 mmHg (P=0.6), respectively. CONCLUSIONS: Subretinal TCA stabilizes visual acuity, decreases FA leakage in eyes with CNV owing to AMD, and does not increase IOP, as seen with intravitreous injections.     

Aqueous humor dynamics in ocular hypertensive patients

PURPOSE: To evaluate the mechanism of the intraocular pressure (IOP) elevation in ocular hypertension (OHT), aqueous humor dynamics were compared in patients with OHT versus age-matched ocular normotensive (NT) volunteers. METHODS: In this retrospective study, one group included patients diagnosed with OHT (IOPs > 21 mm Hg, n = 55) for at least six months. All eye medications were discontinued for at least three weeks before the study visit. A second group included age-matched NT subjects (n = 55) with no eye diseases. The study visit included measurements of IOP by pneumatonometry, aqueous flow and outflow facility by fluorophotometry, anterior chamber depth and corneal thickness by pachymetry and episcleral venous pressure by venomanometry. Uveoscleral outflow and anterior chamber volume were calculated mathematically. RESULTS: Significant differences in the OHT versus the NT groups were as follows: increased IOP (21.4 +/- 0.6 versus 14.9 +/- 0.3 mm Hg, respectively; P < 0.0001), reduced uveoscleral outflow (0.66 +/- 0.11 versus 1.09 +/- 0.11 microL/min; P = 0.005) and reduced fluorophotometric outflow facility (0.17 +/- 0.01 versus 0.27 +/- 0.02 microL/min/mm Hg; P < 0.0001). With respect to age, anterior chamber volume decreased in both groups at a rate of 2.4 +/- 0.3 microL/year (r(2) = 0.5, P <.001) and aqueous flow decreased at a rate of 0.013 +/- 0.005 microL/min/year (r(2) = 0.07, P = 0.005). CONCLUSIONS: The increased IOP in ocular hypertensive patients is caused by a reduction in trabecular outflow facility and uveoscleral outflow. Aqueous flow remains normal. When both ocular normotensive and hypertensive groups are combined, aqueous flow and anterior chamber volume decrease slightly with age.     

Circulating hematopoietic stem cells in patients with neovascular age-related macular degeneration

PURPOSE: Circulating hematopoietic stem cells (HSCs) appear to have roles in the formation of choroidal neovascularization (CNV) in age-related macular degeneration (AMD). This study was conducted to investigate whether the number or function of HSCs plays a role in neovascular AMD. METHODS: Eighty-one patients with neovascular AMD who underwent comprehensive fundus examinations every 3 months were included. The number of CD34(+) HSCs isolated from peripheral blood was counted by flow cytometry. Serum cytokine levels were assessed by enzyme-linked immunosorbent assay. To examine the function of circulating HSCs, mononuclear cells were cultured and then colony forming unit (CFU-EC) and migration were measured. RESULTS: The number of circulating CD34(+) HSCs was significantly increased in the patients with active CNV without major systemic diseases (stable: 3.8 +/- 0.3 cells/microL, active: 5.5 +/- 0.7 cells/microL, stable versus active: P < 0.05). The number of HSCs correlated positively with the erythropoietin serum level (r = 0.47, P = 0.002). Although there was no significant difference in the CFU-EC between the patients with CNV and the control subjects, a significant decrease of CFU-EC was observed in the patients with bilateral or larger CNV. CONCLUSIONS: The findings suggest that CD34(+) HSCs may be recruited from bone marrow through a signal from active CNV. Furthermore, HSCs may play a role in the severity of CNV.     

Macular thickness mapping in exudative age-related macular degeneration

PURPOSE: To report the feasibility of retinal thickness mapping for evaluating thickness differences in retinal areas with and without leakage shown by fluorescein angiography for patients who have age-related macular degeneration with choroidal neovascularization. METHODS: A custom-built version of the retinal thickness analyzer was used for thickness mapping. Retinal thickness was defined as the separation between vitreoretinal and pigment epithelium-choroid interfaces. Imaging was performed in 1 eye of 10 patients with the clinical diagnoses of age-related macular degeneration and choroidal neovascularization. Patients either had never undergone photodynamic therapy at the time of measurement (untreated) or had received one or more photodynamic therapy treatments (treated). Average retinal thicknesses in selected areas with and without the presence of leakage shown by fluorescein angiography were calculated and compared statistically. RESULTS: Retinal thickness (mean +/- SD) in areas with leakage (315 +/- 54 microm) was significantly greater than that in areas without leakage (280 +/- 28 microm) (P = 0.03). In untreated patients, areas with leakage (345 +/- 45 microm) were significantly thicker than areas without leakage (289 +/- 23 microm) (P = 0.02). In treated patients, retinal thickness in areas with leakage (271 +/- 33 microm) and without leakage (267 +/- 34 microm) was similar. CONCLUSION: Retinal thickness mapping may prove to be useful as an adjunct to fluorescein angiography to monitor choroidal neovascularization and its treatment.     

Ocular rigidity evaluation after photorefractive keratectomy: an experimental study

PURPOSE: To evaluate possible changes of the ocular rigidity coefficient in vivo after photorefractive keratectomy (PRK) in a series of rabbit eyes, using an invasive ocular rigidity measurement device. METHODS: Sixteen eyes of 8 rabbits were used in this study. One eye from each rabbit underwent PRK for -10.00 diopters (D) in a 5-mm optical zone (92 microm) while the fellow eye served as the control. Five weeks later, the rabbits were examined under general anesthesia. The pressure-volume relationship and the ocular rigidity coefficient were determined in all 16 eyes, by injecting 200 microL of saline solution (in increments of 4.5 microL) through the limbus into the anterior chamber, while the intraocular pressure (IOP) was continually monitored with a transducer, up to a maximum limit of 40 mmHg. Data within an IOP range of 10 to 40 mmHg were used to calculate the ocular rigidity coefficient. RESULTS: The preoperative central corneal thickness was comparable (P = .73, paired t test) in the pre-PRK eyes (mean: 347.5 +/- 17.11 microm) and control eyes (mean: 349.1 +/- 17.46 microm). No statistically significant difference was noted in measured ocular rigidity coefficient between eyes treated with PRK and control eyes (mean rigidity coefficient: 0.42 +/- 0.12 mmHg/microL [range: 0.23 to 0.56] and 0.47 +/- 0.12 mmHg/microL [range: 0.28 to 0.62], respectively, with 95% confidence interval of the difference, lower: -0.10 to upper: 0.015, P = .121). CONCLUSIONS: Photorefractive keratectomy did not significantly alter ocular rigidity measurements in this experimental model.     

Photodynamic therapy for subfoveal choroidal neovascularisation in Vogt-Koyanagi-Harada disease

AIM: To assess the effects of photodynamic therapy (PDT) with verteporfin in the treatment of subfoveal choroidal neovascularisation (CNV) secondary to Vogt-Koyanagi-Harada disease (VKH). METHODS: Six eyes of six patients with VKH who developed subfoveal CNV underwent standard PDT. Repeated treatments were performed at 3 month intervals for persistent leakage. Charts and angiographic data were analysed retrospectively. RESULTS: Age of patients ranged between 17 years and 27 years. Five CNV lesions were recent and classic (greatest lesion diameter was 1100-3100 microm). One CNV was chronic and partially scarred. Mean visual acuity (VA) at presentation was 20/200. Five patients had more than 1 year of follow up. In five eyes there was active inflammation and CNV. Of these eyes, the first three required one PDT each. The final CNV scar was smaller/stable with improvement of VA in two eyes. The third developed a larger CNV scar with loss of two lines of VA. Submacular fibrosis developed in all three. In the fourth eye, mild CNV leakage persisted after one PDT but hazy media precluded a second PDT. At 18 months the CNV scar and VA were stable. The fifth case, with mild inflammation, required three PDT. The CNV leakage became minimal, the lesion became smaller, and VA improved significantly. The sixth eye with CNV had no inflammation and needed two PDT sessions to halt the CNV leakage. The final lesion was smaller and vision was stable. There were no PDT related complications in our series. CONCLUSION: Photodynamic therapy with verteporfin appears to be a safe and viable treatment option for subfoveal CNV secondary to VKH. It offers a chance for stabilisation or even improvement of vision. Further study is warranted.     

Single-session photodynamic therapy combined with intravitreal bevacizumab for neovascular age-related macular degeneration

PURPOSE: To evaluate the efficacy of combined single-session photodynamic therapy (PDT) and intravitreal bevacizumab (IVB) for treatment of neovascular age-related macular degeneration (AMD). METHODS: In a prospective interventional case series, patients with subfoveal choroidal neovascularization (CNV) underwent PDT followed by 1.25 mg IVB injection. Best-corrected visual acuity (BCVA) and optical coherence tomography (OCT) measurements were repeated at 6-week intervals and fluorescein angiography was performed after 12 weeks and when considered necessary thereafter. Repeat injections of IVB were performed based on fluorescein angiographic evidence of CNV leakage. RESULTS: Fourteen eyes were included in this study. Mean follow-up was 52.4+/-15.2 weeks (range: 26-74 weeks). Initially, mean BCVA was 0.80+/-0.42 logMAR and mean central macular thickness (CMT) was 308+/88 microm. At week 12, BCVA improved to 0.62+/-0.47 logMAR (p=0.006) and CMT reduced to 186+/-53 microm (p=0.003). Corresponding results were 0.53+/-0.52 logMAR (p=0.02) and 193+/-78 microm (p=0.002) after 24 weeks. A second IVB injection was performed in 13 eyes with a mean interval of 16.3+/-5.9 weeks. CONCLUSIONS: Combination therapy with single-session PDT and IVB can improve vision and reduce CMT in neovascular AMD. Repeat IVB injections may maintain the visual gain from the initial combination therapy.     

光动力疗法治疗黄斑中心凹下脉络膜新生血管后激光照射区视网膜厚度的变化

目的探讨光动力疗法（PDT）治疗黄斑中心凹下脉络膜新生血管（CNV）后激光照射区视网膜厚度的变化。方法对25例（27只眼）黄斑中心凹下CNV患者进行PDT治疗,激光光斑直径1．8—4．3mm（平均2．9mm）,应用相干光断层扫描仪（OCT）测量黄斑中心凹和3mm激光照射区平均视网膜厚度,分别比较PDT治疗前和后24h、1周、1和3个月的视网膜厚度。结果PDT治疗前和后24h、1周、1和3个月的黄斑中心凹视网膜厚度分别为（278．07±85．31）、（324．52±96．08）、（242．74±67．40）、（234．26±51．04）μm和（239．73±52．81）μm;3mm激光照射区的平均视网膜厚度分别为（266．71±60．82）、（309．25±82．69）、（257．48±52．48）、（245．44±47．54）μm及（244．88±44．22）μm。PDT治疗前与治疗后24h、1和3个月比较,PDT治疗后24h与1周、1和3个月比较,差异有统计学意义（P〈0．01）。结论PDT激光照射区视网膜厚度在治疗后24h明显增厚,治疗后1周即恢复治疗前水平。提示PDT治疗后激光照射区视网膜水肿的发生可能与CNV渗透、激光照射引起的视网膜和脉络膜血管通透性增加及视网膜色素上皮细胞暂时性功能失代偿有关。（中华聪群杂志．2007．43：505—508）     

Inhibitory effect of bucillamine on laser-induced choroidal neovascularization in rats

PURPOSE: We investigated the inhibitory effects of bucillamine on formation of laser-induced choroidal neovascularization (CNV) in a rat model. METHODS: Bucillamine administration (approximately 150 mg/kg/day) was started 1 week before photocoagulation and continued to the end of the study. Control groups received drinking water. Two weeks after photocoagulation, choroidal neovascularization development was evaluated using simultaneous fluorescein and indocyanine green angiography, and the maximal thickness of the lesions was measured histologically. RESULTS: The incidence of CNV formation was 99.5 +/- 0.2% [mean +/- standard deviation (SD)] in control rats and 64.3 +/- 15.1% with bucillamine (P < 0.01). Histological study showed that the thickness of the CNV lesions was 23.4 +/- 6.5 microm (mean +/- SD) in the bucillamine-treated rats, which was significantly decreased compared to that in controls (60.8 +/- 9.2 microm) (P < 0.01). CONCLUSIONS: Our results suggest that bucillamine may inhibit the development of laser-induced CNV in rats.     

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.     

Low-dose 5-fluorouracil trabeculectomy as initial surgery in uncomplicated glaucoma: long-term followup

OBJECTIVE: To compare the effectiveness of trabeculectomy with adjunctive, low-dose, subconjunctival 5-fluorouracil (5-FU) to trabeculectomy alone in patients with uncomplicated glaucoma undergoing their first incisional surgical procedure. DESIGN: Retrospective, nonrandomized comparative trial. PARTICIPANTS: Consecutive series of 52 patients and 74 control subjects. INTERVENTION: Trabeculectomy was performed in all patients. Study patients received adjunctive, subconjunctival injections of 5-FU up to 14 days from the date of surgery. MAIN OUTCOME MEASURES: Intraocular pressure, number of postoperative antiglaucoma medications, interventions, and complications were evaluated. RESULTS: Mean followup for all patients was 58.1 +/- 44.1 months (range, 1.1-159.9 months). Mean followup for successful eyes was 55.9 +/- 47.1 months (range, 7.6-159.9 months). The cumulative 5-year success (intraocular pressure [IOP] < or = 21 mmHg) was 77.8% in the 5-FU group and 62.2% in the control group (P = 0.02, Wilcoxon test. Complete success (IOP < or = 21 mmHg without medications) at 5 years was lower in both the 5-FU group (72.3%) and the control group (51.3%). Postoperative mean IOP at 5 years for all successful patients was lower in eyes receiving 5-FU (10.7 +/- 3.6 mmHg vs. 16.0 +/- 6.1 mmHg [P = 0.02, t-test]). For those patients considered to be complete successes, there was no difference in IOP between the two groups of patients at any evaluated time interval. Patients in the 5-FU group were using 0.7 +/- 1.1 medications at final followup compared with 1.8 +/- 1.4 medications in the control group (P = < 0.0001, t test). Bleb-related ocular infection occurred in 6.3% of patients and was more common in patients receiving 5-FU than controls (6 of 52 vs 2 of 74, respectively; P = 0.05, Fischer's exact test). CONCLUSIONS: Adjunctive, low-dose 5-FU at the time of initial surgery in uncomplicated glaucoma improves long-term IOP control and reduces the need for postoperative, antiglaucoma therapy. Eyes receiving 5-FU are at greater risk of developing late bleb-related ocular infection.     

Retinal abnormalities in early Alzheimer's disease

PURPOSE: There is evidence suggesting that visual disturbances in patients with Alzheimer's Disease (AD) are due to pathologic changes in the retina and optic nerve, as well as to higher cortical impairment. The purpose of this study was to evaluate retinal hemodynamic parameters and to characterize patterns of retinal nerve fiber layer (RNFL) loss in patients with early AD. METHODS: Nine patients with mild to moderate probable AD (mean Mini Mental State Examination score 24 of a possible 30 (age 74.3 +/- 3.3 years; mean +/- SD) and eight age-matched control subjects (age, 74.3 +/- 5.8 years) were included in this prospective cross-sectional study. Blood column diameter, blood velocity, and blood flow rate were measured in the major superior temporal retinal vein in each subject by using a laser Doppler instrument. Peripapillary RNFL was measured by optical coherence tomography. RESULTS: Patients with AD showed a significant narrowing of the venous blood column diameter (131.7 +/- 10.8 microm) compared with control subjects (148.3 +/- 12.7 microm, P = 0.01), and a significantly reduced venous blood flow rate (9.7 +/- 3.1 microL/min) compared with the control subjects (15.9 +/- 3.7 microL/min, P = 0.002). A significant thinning of the RNFL was found in the superior quadrant in patients with AD (92.2 +/- 21.6 microm) compared with control subjects (113.6 +/- 10.7 microm, P = 0.02). There were no significant differences in the inferior, temporal, or nasal RNFL thicknesses between the groups. CONCLUSIONS: Retinal abnormalities in early AD include a specific pattern of RNFL loss, narrow veins, and decreased retinal blood flow in these veins. The results show that AD produces quantifiable abnormalities in the retina.     

Intravitreal injection of vascular endothelial growth factor small interfering RNA inhibits growth and leakage in a nonhuman primate, laser-induced model of choroidal neovascularization

PURPOSE: To determine the safety and efficacy of small interfering RNA (siRNA) directed against vascular endothelial growth factor (VEGF) in a nonhuman primate model of laser-induced choroidal neovascularization (CNV). METHODS: Each animal received laser rupture of Bruch's membrane to induce CNV in both eyes. Each animal was then randomized to receive 0.05 mL of either vehicle alone or VEGF siRNA at 70 microg, 150 microg, or 350 microg in both eyes by intravitreal injection. Eyes were monitored weekly by ophthalmic examination, color photography, and fluorescein angiography for 36 days after laser injury. Electroretinograms were measured at baseline and at 5 weeks after laser. CNV on fluorescein angiograms were measured for area and graded for clinically significant leakage in a standardized, randomized, and double-masked fashion on days 15, 22, 29, and 36 after laser. RESULTS: VEGF siRNA did not cause any change in electroretinographic, hemorrhage, inflammation, or clinical signs of toxicity. A single administration of VEGF siRNA significantly inhibited growth of CNV and attenuated angiographic leakage in a dose-dependent manner. CONCLUSION: Intravitreal injection of VEGF siRNA is capable of inhibiting the growth and vascular permeability of laser-induced CNV in a nonhuman primate in a dose-dependent manner. This study demonstrates preclinical proof of a principle that supports proceeding to clinical studies of VEGF siRNA in patients with exudative age-related macular degeneration.     

Short-term effects of intravitreal bevacizumab for subfoveal choroidal neovascularization in pathologic myopia

PURPOSE: To determine short-term effects of intravitreal bevacizumab for subfoveal choroidal neovascularization (CNV) in pathologic myopia. METHODS: In this prospective interventional case series, patients were treated with 2.5 mg of intravitreal bevacizumab and followed for 3 months. Best-corrected visual acuity (BCVA), optical coherence tomography (OCT), and fluorescein angiography (FA) were recorded. Indications for retreatment were active leaking CNV shown by FA and presence of subretinal fluid by OCT in combination with visual disturbances. RESULTS: Fourteen patients were included, with a mean age of 53.86 +/- 16.26 years (range 29-85). Mean spherical equivalent was -13.87 +/- 3.68 diopters (-7.25 to -20.50). Minimum follow-up was 3 months. There were no adverse events. The mean initial visual acuity was 20/200 improving to 20/100 at 2 weeks, 20/80 at 4 weeks, and 20/60 at 8 and 12 weeks (P=0.007; P=0.001; P=0.005; P=0.001, respectively). Initial foveal thickness improved from 385.43 microm +/- 125.83 microm to 257.64 +/- 76.6 microm and 194.54 +/- 54.35 microm after the first and third month, respectively (P=0.001). CONCLUSIONS: Initial treatment results of patients with CNV due to pathologic myopia did not reveal any short-term safety concerns. Intravitreal bevacizumab resulted in a significant decrease in foveal thickness and improvement in visual acuity. These favorable initial results support further larger and long-term studies.     

Surgical treatment of subfoveal neovascularization in myopia: macular translocation vs surgical removal

PURPOSE: To compare the visual outcome of two different surgical approaches for subfoveal neovascularization in degenerative myopia: macular translocation and surgical removal of choroidal neovascularization (CNV). DESIGN: Interventional case series. METHODS: Retrospectively, 32 eyes with degenerative myopia (axial length over 26 mm or refraction over -6 diopters) and subfoveal CNV of 32 consecutive patients operated on by either surgical removal of CNV or limited macular translocation were reviewed. Surgical removal of CNV was performed in 18 eyes and limited macular translocation with a twofold suture in 14 eyes. The main outcome measurements were best-corrected visual acuity (BCVA) and findings from fluorescein angiography. Postoperatively, mean +/- SD follow up was 14 +/- 15 months (range, 6-48 months) in the removal group and 11 +/- 4 months (range, 6-24 months, P =.37) in the translocation group. RESULTS: In both groups, there was no significant difference in preoperative age, sex, refractive error, or BCVA. The average of postoperative BCVA was statistically better after macular translocation (10 ETDRS lines or 20/100) than after surgical removal (6 lines 10/125, P =.019). Visual acuity improved by 3.8 lines after macular translocation and was unchanged after surgical removal (-0.7 line, P =.011). Macular translocation was successful in shifting the CNV to an extrafoveal location in 11 out of 14 eyes. Mean foveal displacement of all 18 translocated eyes was 695 +/- 426 microm (range, 100-1520 microm). Recurrence of CNV occurred in seven eyes (39%) after surgical removal and in two eyes (14%) after translocation. Retinal detachment occurred in two eyes in each group. CONCLUSION: In this retrospective study, eyes with degenerative myopia and subfoveal neovascularization treated with limited macular translocation had better visual acuity recovery than eyes treated with surgical removal of the choroidal neovascularization. Further studies are required to confirm these results.     

Evaluation of the Xal-Ease latanoprost delivery system.

PURPOSE: The purpose of this study was to compare drops of latanoprost dispensed using the Xal-Ease (Pfizer Ophthalmics, New York, New York) delivery system with drops dispensed manually. METHODS: Twenty-four 2.5-mL bottles of Xalatan (Pfizer Ophthalmics) were evaluated with or without the delivery system. Individually dispensed drops were counted. The total volume dispensed was measured to the nearest 10 microL. Statistical analysis compared group means by analysis of variance. P values less than 0.05 were considered significant. RESULTS: The overall mean volume was 2,850 microL. Overall mean drops per bottle (n = 24) were 90.3 +/- 6.3. Using the Xal-Ease, mean drops per bottle were 93.0 +/- 3.4 and without it, 87.7 +/- 7.5 (n = 12 each). CONCLUSIONS: With Xal-Ease, mean drops per bottle (5) were statistically significantly greater when compared with standard dispensing (P = 0.0393). This result is accounted for by more consistent individual drop volume and greater volume using the delivery system.     

Photoablative laser-grid trabeculectomy in glaucoma filtering surgery: histology and outflow facility measurements in porcine cadaver eyes

BACKGROUND AND OBJECTIVE: Mid-infrared laser technology opens new perspectives in experimental glaucoma surgery. The aim of the study was to determine the efficacy of grid-laser trabeculectomy to reduce aqueous outflow resistance sufficiently in perfused porcine cadaver eyes. MATERIALS AND METHODS: Twenty-five freshly enucleated porcine cadaver eyes were randomly assigned to either laser-grid trabeculectomy (LGT), conventional trabeculectomy (CT), or control. In all surgical cases a scleral flap was prepared in a standardized manner. In order to penetrate into the anterior chamber a 1 x 2 mm sclerectomy was performed in CT, and 10 transscleral ablation craters were created in LGT. An erbium:YAG laser (2.96 microm) was used for transscleral photoablation. Radiation was delivered in a single 6 mJ-pulse of 200 micros duration by means of an articulated zirconium fluoride optical fiber and a 200 microm quartz fiber-tip. Outflow facility was measured at a constant perfusion pressure. RESULTS: Laser-grid trabeculectomy (LGT) yielded reproducible ablation areas varying between 210-300 microm in diameter, with 90% being full-thickness penetrations. Collateral thermal damage was less than 30 microm. Outflow facility measurements revealed a statistically significant increase (mean +/- SD) from 0.255 +/- 0.096 microL/min/mm Hg in control eyes (n = 9) to 0.772 +/- 0.157 microL/min/mm Hg in the LGT group (n = 9), and 2.957 +/- 0.602 microL/min/mm in the CT group (n = 7). Flattening of the anterior chamber, folding of Descemet's membrane, and iris prolapse were only observed in the CT eyes but not in the GLT group. CONCLUSION: Application of the laser-grid trabeculectomy produces patent transscleral perforation with minimal collateral tissue damage and effects a significant reduction (67%) in outflow resistance without any postoperative hypotony-related complications.     

Macular thickness in patients with choroidal neovascularization determined by RTA and OCT3: comparative results

AIMS: The authors conducted a study to compare retinal thickness in patients with choroidal neovascularization (CNV) using optical coherence tomography (OCT) and retinal thickness analyser (RTA). METHODS: In all, 11 eyes from 11 patients with subfoveal choroidal neovascularization were examined with OCT and RTA. RESULTS: Three patients could not be explored by RTA due to lack of fixation and high myopia. The mean foveal thickness was 289.9+/-92.1 microm with OCT and 207.7+/-60.8 microm with RTA. The mean perifoveal thickness was 293.8+/-46.3 microm and 200.8+/-61.3 microm, respectively. The maximal perifoveal thickness measured by OCT was 335+/-104.0 microm and 316+/-86.8 microm by RTA. CONCLUSION: OCT and RTA are able to detect increases in retinal thickness due to the presence of CNV and of fluid extravasation. They can be used in measuring retinal thickness in patients with CNV, although measures are not comparable between both systems.