Retinal Detachment and Proliferative Vitreoretinopathy.

In normal eyes, retinal detachment (RD) occurs at a rate of approximately 5 per 100,000 people per year and the frequency of proliferative vitreoretinopathy (PVR) remains largely unchanged in primary RD, with the incidence ranging from 5.1 to 11.7%. PVR is the most common cause of failed repair of rhegmatogenous RD, and risk factors for PVR are related to several well-known pre-, intra-, and postoperative clinical situations. Current methods of surgical management of RD and PVR are pneumatic retinopexy, scleral buckling, and pars plana vitrectomy (PPV). Surgical success rates for PVR have improved as techniques and instruments of vitrectomy evolved. However, despite these advances, more than one fourth of initially successful cases results in redetachment due to recurrent vitreoretinal traction. Retinal pigment epithelial cells are the key factor in triggering PVR development. In addition, soluble mediators and the extracellular matrix components play a critical role in cellular events, including proliferation and tissue contraction which occur in PVR. Although PPV remains a critical component of the treatment in RD and PVR, ongoing efforts seek to identify adjuvant therapies that might inhibit PVR development. Recent studies have therefore been directed toward pharmacologic inhibition of cellular proliferation and membrane contraction with drugs such as daunorubicin, 5-fluorouracil, and heparin. More detailed understanding of the pathophysiology underlying PVR may lead to the development of effective prophylactic and/or adjunctive therapies. Further work is necessary to identify optimal adjunctive therapies for the management of RD and PVR.

Induction of WNT inhibitory factor 1 expression by Müllerian inhibiting substance/antiMullerian hormone in the Müllerian duct mesenchyme is linked to Müllerian duct regression.

A key event during mammalian sexual development is regression of the Müllerian ducts (MDs) in the bipotential urogenital ridges (UGRs) of fetal males, which is caused by the expression of Müllerian inhibiting substance (MIS) in the Sertoli cells of the differentiating testes. The paracrine signaling mechanisms involved in MD regression are not completely understood, particularly since the receptor for MIS, MISR2, is expressed in the mesenchyme surrounding the MD, but regression occurs in both the epithelium and mesenchyme. Microarray analysis comparing MIS signaling competent and Misr2 knockout embryonic UGRs was performed to identify secreted factors that might be important for MIS-mediated regression of the MD. A seven-fold increase in the expression of Wif1, an inhibitor of WNT/ß-catenin signaling, was observed in the Misr2-expressing UGRs. Whole mount in situ hybridization of Wif1 revealed a spatial and temporal pattern of expression consistent with Misr2 during the window of MD regression in the mesenchyme surrounding the MD epithelium that was absent in both female UGRs and UGRs knocked out for Misr2. Knockdown of Wif1 expression in male UGRs by Wif1-specific siRNAs beginning on embryonic day 13.5 resulted in MD retention in an organ culture assay, and exposure of female UGRs to added recombinant human MIS induced Wif1 expression in the MD mesenchyme. Knockdown of Wif1 led to increased expression of ß-catenin and its downstream targets TCF1/LEF1 in the MD mesenchyme and to decreased apoptosis, resulting in partial to complete retention of the MD. These results strongly suggest that WIF1 secretion by the MD mesenchyme plays a role in MD regression in fetal males.

Evidence for baseline retinal pigment epithelium pathology in the Trp1-Cre mouse.

The increasing popularity of the Cre/loxP recombination system has led to the generation of numerous transgenic mouse lines in which Cre recombinase is expressed under the control of organ- or cell-specific promoters. Alterations in retinal pigment epithelium (RPE), a multifunctional cell monolayer that separates the retinal photoreceptors from the choroid, are prevalent in the pathogenesis of a number of ocular disorders, including age-related macular degeneration. To date, six transgenic mouse lines have been developed that target Cre to the RPE under the control of various gene promoters. However, multiple lines of evidence indicate that high levels of Cre expression can be toxic to mammalian cells. In this study, we report that in the Trp1-Cre mouse, a commonly used transgenic Cre strain for RPE gene function studies, Cre recombinase expression alone leads to RPE dysfunction and concomitant disorganization of RPE layer morphology, large areas of RPE atrophy, retinal photoreceptor dysfunction, and microglial cell activation in the affected areas. The phenotype described herein is similar to previously published reports of conditional gene knockouts that used the Trp1-Cre mouse, suggesting that Cre toxicity alone could account for some of the reported phenotypes and highlighting the importance of the inclusion of Cre-expressing mice as controls in conditional gene targeting studies.

Utilizing targeted gene therapy with nanoparticles binding alpha v beta 3 for imaging and treating choroidal neovascularization.

PURPOSE: The integrin αvß3 is differentially expressed on neovascular endothelial cells. We investigated whether a novel intravenously injectable αvß3 integrin-ligand coupled nanoparticle (NP) can target choroidal neovascular membranes (CNV) for imaging and targeted gene therapy. METHODS: CNV lesions were induced in rats using laser photocoagulation. The utility of NP for in vivo imaging and gene delivery was evaluated by coupling the NP with a green fluorescing protein plasmid (NP-GFPg). Rhodamine labeling (Rd-NP) was used to localize NP in choroidal flatmounts. Rd-NP-GFPg particles were injected intravenously on weeks 1, 2, or 3. In the treatment arm, rats received NP containing a dominant negative Raf mutant gene (NP-ATPµ-Raf) on days 1, 3, and 5. The change in CNV size and leakage, and TUNEL positive cells were quantified. RESULTS: GFP plasmid expression was seen in vivo up to 3 days after injection of Rd-NP-GFPg. Choroidal flatmounts confirmed the localization of the NP and the expression of GFP plasmid in the CNV. Treating the CNV with NP-ATPµ-Raf decreased the CNV size by 42% (P<0.001). OCT analysis revealed that the reduction of CNV size started on day 5 and reached statistical significance by day 7. Fluorescein angiography grading showed significantly less leakage in the treated CNV (P<0.001). There were significantly more apoptotic (TUNEL-positive) nuclei in the treated CNV. CONCLUSION: Systemic administration of αvß3 targeted NP can be used to label the abnormal blood vessels of CNV for imaging. Targeted gene delivery with NP-ATPµ-Raf leads to a reduction in size and leakage of the CNV by induction of apoptosis in the CNV.

In vivo evaluation of laser-induced choroidal neovascularization using spectral-domain optical coherence tomography.

PURPOSE: To describe the in vivo evolution of laser-induced choroidal neovascularization (CNV) in mice using spectral domain optical coherence tomography (SD-OCT). METHODS: Laser photocoagulation was applied to the mouse fundus using a 532-nm diode laser (100, 150, and 200 mW; 100-µm diameter, 0.1-second duration). SD-OCT examination was performed immediately after laser application and at days 3, 5, 7, 14, 21, and 28 after laser. Fluorescein angiography (FA) was performed at day 5, 7, 14, and 28. Acquired SD-OCT images were analyzed to describe morphologic features, measure CNV size and retinal thickness, and assess the frequency of lesions resulting in fluid accumulation. Finally, SD-OCT images were compared to fluorescein angiograms and histologic sections with immunostaining at similar time points. RESULTS: SD-OCT allowed visualization of the initial laser damage and the subsequent stages of the injury response. CNV formation reached its maximum size at day 5. By day 7, significant size reduction was observed (P < 0.001), continuing through days 14 and 28. Exudation signs, such as fluid accumulation and increase in retinal thickness, followed the same time course, with a peak at day 5 and a decrease by day 7. Delivery of higher laser energy levels to the RPE/choroid complex resulted in a significant percentage of lesions demonstrating excessive chorioretinal damage without CNV formation. CONCLUSIONS: SD-OCT is a fast and reliable tool for the in vivo evaluation of laser-induced CNV, allowing quantification of lesion size and exudation parameters. Moreover, it provides morphologic information that correlates with histologic findings.

Edaravone, an ROS scavenger, ameliorates photoreceptor cell death after experimental retinal detachment.

PURPOSE: To investigate whether edaravone (3-methyl-1-phenyl-2-pyrazolin-5-one), a free radical scavenger, would be neuroprotective against photoreceptor cell death in a rat model of retinal detachment (RD). METHODS: RD was induced in adult Brown Norway rats by subretinal injection of sodium hyaluronate. Edaravone (3, 5, or 10 mg/kg) or physiologic saline was administered intraperitoneally once a day until death on day 3 or 5. Oxidative stress in the retina was assessed by 4-hydroxynonenal staining or ELISA for protein carbonyl content. Photoreceptor death was assessed by TUNEL and measurement of the outer nuclear layer thickness. Western blot analysis and caspase activity assays were performed. Inflammatory cytokine secretion and inflammatory cell infiltration were evaluated by ELISA and immunostaining, respectively. RESULTS: RD resulted in increased generation of ROS. Treatment with 5 mg/kg edaravone significantly reduced the ROS level, along with a decrease in TUNEL-positive cells in the photoreceptor layer. A caspase assay also confirmed decreased activation of caspase-3, -8, and -9 in RD treated with edaravone. The level of the antiapoptotic Bcl-2 was increased in detached retinas after edaravone treatment, whereas the levels of the stress-activated p-ERK1/2 were decreased. In addition, edaravone treatment resulted in a significant decrease in the levels of TNF-α, MCP-1, and macrophage infiltration. CONCLUSIONS: Oxidative stress plays an important role in photoreceptor cell death after RD. Edaravone treatment may aid in preventing photoreceptor cell death after RD by suppressing ROS-induced photoreceptor damage.

Features of optical coherence tomography are predictive of visual outcomes after intravitreal bevacizumab injection for diabetic macular edema.

PURPOSE: To identify optical coherence tomography (OCT) patterns of diabetic macular edema (DME) predictive of visual outcomes after intravitreal bevacizumab (IVB; Avastin®) injection. METHODS: We retrospectively examined 56 consecutive eyes that were given IVB injections for DME alongside the preoperative macular OCT data. Using this information, we categorized the eyes into 2 groups: group 1 showing diffuse patterns; group 2 demonstrating cystoid macular edema (CME). RESULT: The mean follow-up period was 11.66 ± 3.98 months. Group 1 eyes gained 0.04 ± 9.27 ETDRS letters (p = 0.984), while group 2 eyes gained 5.79 ± 9.98 ETDRS letters (p = 0.005). Mean macular thickness decreased by 72.79 ± 145.74 µm in group 1 (p = 0.014) and by 223.71 ± 224.52 µm in group 2 (p< 0.001). CONCLUSION: Patients showing CME upon OCT achieved greater improvements in visual acuity and macular thickness after IVB injection than patients with diffuse macular edema. The type of macular edema shown by OCT may provide an objective guideline in predicting the response of DME to IVB injection.

Intravitreal triamcinolone acetonide versus bevacizumab therapy for macular edema associated with branch retinal vein occlusion.

PURPOSE: To compare visual outcomes after intravitreal triamcinolone acetonide (IVTA) injection and intravitreal bevacizumab (IVB) administration for treatment of macular edema associated with branch retinal vein occlusion (BRVO). METHODS: A retrospective comparative case series of 134 consecutive patients that were treated with either IVTA or IVB for macular edema caused by BRVO. Visual acuity at baseline and 1, 3, 6, 9, and 12 months, and central macular thickness measured by OCT at baseline and 1, 3, 6, and 12 months. The time to recurrence of macular edema after treatment was also analyzed. RESULTS: Visual acuity (Snellen equivalent) improved significantly from 0.87 logMAR (0.14) to 0.49 logMAR (0.33) in the IVTA group, and from 0.91 logMAR (0.13) to 0.45 logMAR (0.36) in the IVB group 12 months after injection (p < 0.001). Central macular thickness decreased significantly from 491.0 microm to 255.8 microm in the IVTA group, and from 477.4 microm to 218.9 microm in the IVB group 12 months after injection (p < 0.001). In between-group comparisons, neither visual acuity (p = 0.892) nor macular thickness (p = 0.612) improvements were statistically significantly different. In the IVTA-all group, recurrence of macular edema occurred in 7.6% of patients at a mean of 12.6 months postoperatively, and the average number of injections was 1.08. In the IVB-all group, 26.0% of patients suffered recurrences at a mean of 5.3 months after treatment, and received a mean of 1.89 injections. Recurrence was more frequent in the IVB group compared to the IVTA group (Kaplan-Meier survival analysis log-rank test, p < 0.0001). CONCLUSIONS: IVTA and IVB injections were similarly effective for improving visual acuity in patients with macular edema secondary to BRVO. However, the IVTA group showed longer mean improvement duration and less disease recurrence, and required fewer injections than the IVB group.

Intravitreal bevacizumab injection for central serous chorioretinopathy.

PURPOSE: The purpose of this study was to evaluate the effectiveness of intravitreal injection of bevacizumab for treatment of central serous chorioretinopathy. METHODS: In this retrospective case series, six patients (six eyes) with central serous chorioretinopathy were treated with an intravitreal injection of bevacizumab. The outcome measures included visual acuity with Early Treatment Diabetic Retinopathy Study letters, central macular thickness measurement with optical coherence tomography, changes in fluorescein angiography, and indocyanine green angiography. RESULTS: The mean age of the patients was 42.3 years and the mean follow-up period was 9.0 months (range, 5-12 months). Mean visual acuity +/- standard deviation increased from 40.8 +/- 8.3 Early Treatment Diabetic Retinopathy Study letters at baseline to 49.0 +/- 5.0 Early Treatment Diabetic Retinopathy Study letters at 1 month (P = 0.046) and to 53.3 +/- 5.2 Early Treatment Diabetic Retinopathy Study letters at 3 months (P = 0.028). Mean central macular thickness +/- standard deviation decreased from 331.5 +/- 93.4 microm to 164 +/- 34 microm at 3 months (P = 0.043). Leakage on fluorescein angiography and hyperpermeability on indocyanine green angiography decreased in conjunction with improvement in central macular thickness observed by optical coherence tomography. CONCLUSION: Intravitreal bevacizumab injections resulted in improved visual acuity and anatomical results for central serous chorioretinopathy.

Concentration of cytokines in age-related macular degeneration after consecutive intravitreal bevacizumab injection.

BACKGROUND: To evaluate the changes in aqueous humor cytokine levels following consecutive intravitreal bevacizumab (Avastin, Genentech Inc., San Francisco, CA, USA) injections in eyes with choroidal neovascularization (CNV) due to age-related macular degeneration (AMD). METHOD: Aqueous humor samples were collected at the time of intravitreal injection of 1.25 mg of bevacizumab every 7.0 (+/-2.0) weeks from ten eyes with AMD for the AMD group and during cataract surgery in nine eyes for the control group. Visual acuity with Early Treatment of Diabetic Retinopathy Study (ETDRS) letters and central macular thickness (CMT) using optical coherence tomography were measured before each injection in the AMD group. Aqueous cytokine levels were determined by immunoassay using multi-analyte biochip array technology (Evidence investigator cytokine and growth factor biochip array, RANDOX laboratories Ltd., Crumlin, UK). RESULT: In the AMD group, mean +/- standard deviation(SD) aqueous VEGF levels decreased from 68.0 +/- 32.1 pg/ml at baseline to 26.3 +/- 19.0 pg/ml after the first injection (p = 0.028) and to 25.2 +/- 12.8 pg/ml after the second injection (p = 0.005). While CMT decreased from 307.7 +/- 102.0 mum to 206.8 +/- 141.5 microm (p = 0.037), ETDRS visual acuity increased from 17.6 +/- 11.7 letters to 22.0 +/- 15.6 letters after three consecutive injections (p = 0.017). CONCLUSION: Significantly decreased VEGF levels were noted after the first injection of bevacizumab. These levels were maintained after the second injection, which paralleled the change in visual acuity and CMT.

Concentration of cytokines in the aqueous humor of patients with naive, recurrent and regressed CNV associated with amd after bevacizumab treatment.

PURPOSE: : To evaluate the concentration of various cytokines in the aqueous humor of patients with naive, recurrent, and regressed choroidal neovascularization (CNV) of age-related macular degeneration after bevacizumab treatment. METHODS: : Aqueous humor samples were collected from 36 eyes with age-related macular degeneration and 10 controls during cataract surgery. Of 36 patients with age-related macular degeneration, 5 eyes were naïve to bevacizumab injection, 14 eyes had recurrent CNV after bevacizumab treatment, and 17 eyes had regressed CNV after bevacizumab treatment. Cytokines were measured by an immunoassay using multianalyte biochip array technology (Evidence investigator cytokine and growth factor biochip array, RANDOX laboratories Ltd., Crumlin, UK). RESULTS: : No significant difference in the cytokine levels was noted between the control group and the naïve CNV group (all P > 0.05). Vascular endothelial growth factor in both naive (66.8 +/- 35.1 pg/mL) and recurrent CNV groups (55.7 +/- 63.0 pg/mL) was significantly higher compared with regressed CNV group (9.8 +/- 12.8 pg/mL, P = 0.025 and P = 0.004, respectively) but was not statistically different from the control group (81.8 +/- 43.7 pg/mL, P = 0.310 and P = 0.212, respectively). The aqueous humor level of tumor necrosis factor-alpha and interleukin (IL)-2 was significantly lower in recurrent CNV group (P = 0.036 and P = 0.019) compared with the control group. In the active CNV patients (recurrent and naïve CNV groups), the aqueous humor levels of IL-6 and IL-8 significantly correlated with the size of CNV (rho = 0.692, P = 0.001 and rho = 0.745, P < 0.001, respectively). CONCLUSION: : Levels of Vascular endothelial growth factor measured in the aqueous humor were significantly related to the disease activity of CNV in age-related macular degeneration. Moreover, IL-2, IL-6, IL-8, and tumor necrosis factor-alpha may be related to the activity of CNV.

Effect of intravitreal bevacizumab injection on aqueous humor cytokine levels in clinically significant macular edema.

PURPOSE: To determine the effect of intravitreal bevacizumab (Avastin, Genentech, Inc., San Francisco, CA) injection on aqueous humor cytokine levels in clinically significant macular edema (CSME). DESIGN: Retrospective, comparative study. PARTICIPANTS: Seventeen eyes undergoing intravitreal injection for CSME and 11 eyes undergoing cataract surgery as negative controls. Nine patients with CSME were naïve to intravitreal bevacizumab injection (CSME group 1), and 8 patients previously received 1 intravitreal bevacizumab injection at a mean of 9.6+/-1.4 weeks earlier (CSME group 2). METHODS: Aqueous humor samples were collected before performing intravitreal injection in the CSME group and during cataract surgery in the control group. Aqueous cytokine levels were determined by immunoassay using multianalyte biochip array technology. MAIN OUTCOME MEASURES: The concentration of cytokines in the aqueous humor was recorded as a mean (+/- standard deviation) in CSME groups 1 and 2 and the control group. Correlations of aqueous humor cytokine levels were evaluated. RESULTS: Significantly higher levels of interleukin (IL)-6, IL-8, and monocyte chemoattractant protein (MCP)-1 were noted in patients with CSME compared with controls. Although higher vascular endothelial growth factor (VEGF) levels were noted in CSME group 1 (P = 0.001), a lower level of VEGF was noted after intravitreal bevacizumab injection in CSME group 2 (P = 0.004) compared with the control group. VEGF levels were also lower in CSME group 2 compared with CSME group 1 (P = 0.001). In CSME group 2, a significant negative correlation was observed between VEGF and IL-6 (rho = -0.833, P = 0.01) and VEGF and MCP-1 (rho = -0.736, P = 0.037). CONCLUSIONS: Significantly higher levels of IL-6, IL-8, VEGF, and MCP-1 were noted in the aqueous humor of CSME. However, recurrence of macular edema was noted with significantly lower concentrations of VEGF after a single intravitreal injection of bevacizumab. This suggests the potential importance of IL-6 and MCP-1 in the pathogenesis of CSME. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Estimated prevalence and risk factor for age-related maculopathy.

PURPOSE: To assess the estimate prevalence and risk factors for age-related maculopathy (ARM) in Seoul, Korea. PATIENTS AND METHODS: We examined 9,530 subjects with, 40 years of age or older between January 2006 and December 2006 in Seoul, Korea. Subjects underwent fundus photography, clinical examinations (including blood analyses), and completed detailed questionnaires. Fundus images were graded according to definitions from the Wisconsin Age-Related Maculopathy Grading System. RESULTS: ARM was present in 235 subjects, corresponding to an estimate prevalence of 2.46%. Hepatitis B infection (positive status for HBsAg and HBcAb), serum triglyceride levels and high density lipoprotein levels remained as significant risk factors after age-adjustment. Multivariate analyses showed that the prevalence of ARM was significantly higher in older subjects [odds ratio (OR) 1.134; 95% CI 1.114-1.154] and those who were seropositive for hepatitis B surface antigen (OR 2.566; 95% CI 1.519-4.335). CONCLUSION: The estimated prevalence of ARM was 2.46%. Age and hepatitis B infection may increase the risk of ARM.

Prevalence of and risk factors for asteroid hyalosis in Seoul, Korea.

PURPOSE: To estimate the prevalence of asteroid hyalosis (AH) in Seoul, Korea, and to identify risk factors for the condition. METHODS: A cross-sectional study with review of fundus photographs of subjects who received a health check-up between January 2006 and December 2006 at the Yonsei Medical Examination Center yielded 9,050 available cases (aged 40 years or older). AH was diagnosed retrospectively by the presence of cream-white spherical bodies within the vitreous, as seen in the fundus photographs. RESULTS: The estimate prevalence of AH was 0.36%. Multivariate analysis showed that the prevalence of AH was significantly higher in older patients and in those with stroke history, hypertension history, and high serum lipid levels. CONCLUSION: AH was relatively uncommon with the estimate prevalence of 0.36% in Seoul, Korea. The prevalence of AH correlated with age, stroke history, hypertension history, serum triglyceride levels, and low-density lipoprotein levels, with no gender bias. AH was not significantly associated with a history of diabetes, gout, heavy drinking, or current smoking.

Effects of macular ischemia on the outcome of intravitreal bevacizumab therapy for diabetic macular edema.

PURPOSE: To evaluate the effects of macular ischemia on visual outcomes in patients with diabetic macular edema (DME), after intravitreal bevacizumab injections. METHODS: Data on 59 eyes of 53 consecutive patients treated with intravitreal bevacizumab for DME were retrospectively reviewed. Data from preoperative fluorescein angiography (FA) tests were examined. Patients with an enlarged foveal avascular zone (FAZ), >or=1000 microm, or a broken perifoveal capillary ring at the border of the FAZ, with a distinct area of capillary nonperfusion within one disk diameter of the foveal center in the transit phase of fluorescein angiography, were defined as having macular ischemia. The patients were thus divided into two groups: with or without macular ischemia. Early Treatment Diabetic Retinopathy Study (ETDRS) scores, and foveal thicknesses measured using third generation ocular coherence tomography (OCT), were evaluated at baseline and at 1 month and 3 months after treatment. RESULTS: At 3 months after treatment, the mean visual acuity (VA) score decreased from a baseline VA of 0.52 +/- 0.27 (approximate Snellen equivalent, 20/63) to 0.57 +/- 0.21 (20/80) in the ischemic group. In the nonischemic group, by contrast, the VA improved from 0.66 +/- 0.34 (20/100) at baseline to 0.59 +/- 0.33 (20/80) at 3 months post-treatment. Nine of 18 eyes (50%) in the ischemic group, but only 9 of 41 eyes (21%) in the nonischemic group, experienced visual losses of >or=1 line on the ETDRS chart (P = 0.031, Pearson chi-square test). Four eyes (22%) in the ischemic group, but only 2 eyes (5%) in the nonischemic group, lost >or=3 lines (P = 0.042, Pearson chi-square test). CONCLUSION: Macular ischemia may have a negative effect on short term visual outcomes after intravitreal bevacizumab injections in patients with DME.

Repeated intravitreal injection of bevacizumab for clinically significant diabetic macular edema.

PURPOSE: Intravitreal bevacizumab (Avastin) induces a transient improvement in diabetic macular edema, necessitating repeated injections. Here, we report the results of repeated administration of intravitreal bevacizumab for the treatment of clinically significant macular edema in 31 eyes of 24 patients. METHODS: At preinjection and 1, 6, and 12 (+/-1) weeks postinjection, visual acuity (VA) with Early Treatment of Diabetic Retinopathy Study (ETDRS) and central macular thickness (CMT) evaluated using optical coherence tomography were compared with independent and paired t-tests. RESULTS: VA and CMT were not significantly different before initial and repeated injections (administered at an interval of 22.06 +/- 11.15 [SD] weeks). At 6 weeks after the first injection, VA increased significantly by 3.72 +/- 8.02 ETDRS letters (P = 0.019), and CMT was markedly decreased by 93.30 +/- 210.33 microm (P = 0.022), which returned to near baseline at 12 weeks. At 6 weeks after the second injection, VA increased significantly by 3.97 +/- 7.46 ETDRS letters (P = 0.006) and CMT decreased considerably by 118.77 +/- 178.58 microm (P = 0.001). At 12 weeks after the second injection, we observed a decrease in VA with recurrence of macular edema. CONCLUSIONS: Repeated administration of intravitreal bevacizumab (1.25 mg) may lead to the improvement of VA and CMT in patients with clinically significant macular edema.

Deposits of transforming growth factor-beta-induced protein in granular corneal dystrophy type II after LASIK.

PURPOSE: To analyze components of the deposits in the corneal flap interface of granular corneal dystrophy type II (GCD II) patients after laser in situ keratomileusis (LASIK). METHODS: Four corneal GCD II specimens displaying disease exacerbation after LASIK were analyzed. Three of these specimens included the recipient corneal button after penetrating keratoplasty or deep lamellar keratoplasty for advanced GCD II after LASIK. The fourth specimen, a similar case of GCD II after LASIK, included the amputated corneal flap. Specimens were processed for histopathologic and immunohistochemical analyses. RESULTS: Corneal stromal deposits in the LASIK flaps of all specimens were stained with 3 anti-transforming growth factor-beta-induced protein (TGFBIp) antibodies. The deposits displayed bright red color staining with Masson trichrome; however, negative staining was seen with Congo red, suggesting that hyaline is the main component localizing to the TGFBIp deposits rather than amyloid. CONCLUSIONS: Amorphous granular material deposited along the interface of the LASIK flap in GCD II corneas is composed mainly of hyaline deposits.

Mycobacterium abscessus keratitis after LASIK with IntraLase femtosecond laser.

A healthy 38-year-old woman developed 2 white spots in her left eye 2 weeks after bilateral laser in situ keratomileusis (LASIK) using the IntraLase femtosecond laser. Initial treatment included levofloxacin 0.5% but was unsuccessful. The surgeon irrigated the interface and repositioned the flap due to a worsened lesion. She was referred to us after the keratitis had not improved. The flap was lifted for collection of the specimen and irrigation of the interface. The keratitis was treated with intensive topical clarithromycin 1%, amikacin 1.25% and oral clarithromycin, which improved her clinical condition. She developed a toxic reaction to amikacin 1.25%, which was replaced by moxifloxacin 0.5%. Mycobacterium abscessus was identified. The keratitis resolved over 2 months. Five months after treatment, the patient had a visual acuity of 20/20 with correction. Nontuberculous mycobacteria should be considered as an etiologic agent, even in cases of infectious keratitis after LASIK using the femtosecond laser.

Avellino corneal dystrophy exacerbated after LASIK: scanning electron microscopic findings.

PURPOSE: To evaluate the ultrastructure of the cornea of Avellino corneal dystrophy (ACD) exacerbated by LASIK. METHODS: Three ACD patients with exacerbation of granular corneal deposits after LASIK underwent surgical removal of the corneal flap. The corneal flap was processed for scanning electron microscopy (SEM). RESULTS: SEM of all patients showed abnormal granular clusters in the fibrils of the corneal flap. CONCLUSION: Laser in situ keratomileusis induces corneal collagen abnormalities and adhesions of granular material in ACD patients.