Increasing ATP turnover boosts productivity of 2,3-butanediol synthesis in Escherichia coli.

BACKGROUND: The alcohol 2,3-butanediol (2,3-BDO) is an important chemical and an Escherichia coli producer strain was recently engineered for bio-based production of 2,3-BDO. However, further improvements are required for realistic applications. RESULTS: Here we report that enforced ATP wasting, implemented by overexpressing the genes of the ATP-hydrolyzing F1-part of the ATPase, leads to significant increases of yield and especially of productivity of 2,3-BDO synthesis in an E. coli producer strain under various cultivation conditions. We studied aerobic and microaerobic conditions as well as growth-coupled and growth-decoupled production scenarios. In all these cases, the specific substrate uptake and 2,3-BDO synthesis rate (up to sixfold and tenfold higher, respectively) were markedly improved in the ATPase strain compared to a control strain. However, aerobic conditions generally enable higher productivities only with reduced 2,3-BDO yields while high product yields under microaerobic conditions are accompanied with low productivities. Based on these findings we finally designed and validated a three-stage process for optimal conversion of glucose to 2,3-BDO, which enables a high productivity in combination with relatively high yield. The ATPase strain showed again superior performance and finished the process twice as fast as the control strain and with higher 2,3-BDO yield. CONCLUSIONS: Our results demonstrate the high potential of enforced ATP wasting as a generic metabolic engineering strategy and we expect more applications to come in the future.

Temperature-dependent dynamic control of the TCA cycle increases volumetric productivity of itaconic acid production by Escherichia coli.

Based on the recently constructed Escherichia coli itaconic acid production strain ita23, we aimed to improve the productivity by applying a two-stage process strategy with decoupled production of biomass and itaconic acid. We constructed a strain ita32 (MG1655 ΔaceA Δpta ΔpykF ΔpykA pCadCs), which, in contrast to ita23, has an active tricarboxylic acid (TCA) cycle and a fast growth rate of 0.52 hr-1 at 37°C, thus representing an ideal phenotype for the first stage, the growth phase. Subsequently we implemented a synthetic genetic control allowing the downregulation of the TCA cycle and thus the switch from growth to itaconic acid production in the second stage. The promoter of the isocitrate dehydrogenase was replaced by the Lambda promoter (pR ) and its expression was controlled by the temperature-sensitive repressor CI857 which is active at lower temperatures (30°C). With glucose as substrate, the respective strain ita36A grew with a fast growth rate at 37°C and switched to production of itaconic acid at 28°C. To study the impact of the process strategy on productivity, we performed one-stage and two-stage bioreactor cultivations. The two-stage process enabled fast formation of biomass resulting in improved peak productivity of 0.86 g/L/hr (+48%) and volumetric productivity of 0.39 g/L/hr (+22%) in comparison to the one-stage process. With our dynamic production strain, we also resolved the glutamate auxotrophy of ita23 and increased the itaconic acid titer to 47 g/L. The temperature-dependent activation of gene expression by the Lambda promoters (pR /pL ) has been frequently used to improve protein or, in a few cases, metabolite production in two-stage processes. Here we demonstrate that the system can be as well used in the opposite direction to selectively knock-down an essential gene (icd) in E. coli to design a two-stage process for improved volumetric productivity. The control by temperature avoids expensive inducers and has the potential to be generally used to improve cell factory performance.

Valacyclovir versus acyclovir for the treatment of herpes zoster ophthalmicus in immunocompetent patients.

BACKGROUND: Herpes zoster ophthalmicus affects the eye and vision, and is caused by the reactivation of the varicella zoster virus in the distribution of the first division of the trigeminal nerve. An aggressive management of acute herpes zoster ophthalmicus with systemic antiviral medication is generally recommended as the standard first-line treatment for herpes zoster ophthalmicus infections. Both acyclovir and its prodrug valacyclovir are medications that are approved for the systemic treatment of herpes zoster. Although it is known that valacyclovir has an improved bioavailability and steadier plasma concentration, it is currently unclear as to whether this leads to better treatment results and less ocular complications. OBJECTIVES: To assess the effects of valacyclovir versus acyclovir for the systemic antiviral treatment of herpes zoster ophthalmicus in immunocompetent patients. SEARCH METHODS: We searched CENTRAL (which contains the Cochrane Eyes and Vision Trials Register; 2016, Issue 5), Ovid MEDLINE, Ovid MEDLINE In-Process and Other Non-Indexed Citations, Ovid MEDLINE Daily, Ovid OLDMEDLINE (January 1946 to June 2016), Embase (January 1980 to June 2016), Web of Science Conference Proceedings Citation Index-Science (CPCI-S; January 1990 to June 2016), BIOSIS Previews (January 1969 to June 2016), the ISRCTN registry (www.isrctn.com/editAdvancedSearch), ClinicalTrials.gov (www.clinicaltrials.gov), and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP; www.who.int/ictrp/search/en). We did not use any date or language restrictions in the electronic searches for trials. We last searched the electronic databases on 13 June 2016. SELECTION CRITERIA: We considered all randomised controlled trials (RCTs) in which systemic valacyclovir was compared to systemic acyclovir medication for treatment of herpes zoster ophthalmicus. There were no language restrictions. DATA COLLECTION AND ANALYSIS: Two review authors independently selected trials, evaluated the risk of bias in included trials, and extracted and analysed data. We did not conduct a meta-analysis, as only one study was included. We assessed the certainty of the evidence for the selected outcomes using the GRADE approach. MAIN RESULTS: One study fulfilled the inclusion criteria. In this multicentre, randomised double-masked study carried out in France, 110 immunocompetent people with herpes zoster ophthalmicus, diagnosed within 72 hours of skin eruption, were treated, with 56 participants allocated to the valacyclovir group and 54 to the acyclovir group. The study was poorly reported and we judged it to be unclear risk of bias for most domains.Persistent ocular lesions after 6 months were observed in 2/56 people in the valacyclovir group compared with 1/54 people in the acyclovir group (risk ratio (RR) 1.93 (95% CI 0.18 to 20.65); very low certainty evidence. Dendritic ulcer appeared in 3/56 patients treated with valacyclovir, while 1/54 suffered in the acyclovir group (RR 2.89; 95% confidence interval (CI) 0.31 to 26.96); very low certainty evidence), uveitis in 7/56 people in the valacyclovir group compared with 9/54 in the acyclovir group (RR 0.96; 95% CI 0.36 to 2.57); very low certainty evidence). Similarly, there was uncertainty as to the comparative effects of these two treatments on post-herpetic pain, and side effects (vomiting, eyelid or facial edema, disseminated zoster). Due to concerns about imprecision (small number of events and large confidence intervals) and study limitations, the certainty of evidence using the GRADE approach was rated as low to very low for the use of valacyclovir compared to acyclovir. AUTHORS' CONCLUSIONS: This review included data from only one study, which had methodological limitations. As such, our results indicated uncertainty of the relative benefits and harms of valacyclovir over acyclovir in herpes zoster ophthalmicus, despite its widespread use for this condition. Further well-designed and adequately powered trials are needed. These trials should include outcomes important to patients, including compliance.

Model-based metabolic engineering enables high yield itaconic acid production by Escherichia coli.

Itaconic acid is a high potential platform chemical which is currently industrially produced by Aspergillus terreus. Heterologous production of itaconic acid with Escherichia coli could help to overcome limitations of A. terreus regarding slow growth and high sensitivity to oxygen supply. However, the performance achieved so far with E. coli strains is still low. We introduced a plasmid (pCadCS) carrying genes for itaconic acid production into E. coli and applied a model-based approach to construct a high yield production strain. Based on the concept of minimal cut sets, we identified intervention strategies that guarantee high itaconic acid yield while still allowing growth. One cut set was selected and the corresponding genes were iteratively knocked-out. As a conceptual novelty, we pursued an adaptive approach allowing changes in the model and initially calculated intervention strategy if a genetic modification induces changes in byproduct formation. Using this approach, we iteratively implemented five interventions leading to high yield itaconic acid production in minimal medium with glucose as substrate supplemented with small amounts of glutamic acid. The derived E. coli strain (ita23: MG1655 ∆aceA ∆sucCD ∆pykA ∆pykF ∆pta ∆Picd::cam_BBa_J23115 pCadCS) synthesized 2.27g/l itaconic acid with an excellent yield of 0.77mol/(mol glucose). In a fed-batch cultivation, this strain produced 32g/l itaconic acid with an overall yield of 0.68mol/(mol glucose) and a peak productivity of 0.45g/l/h. These values are by far the highest that have ever been achieved for heterologous itaconic acid production and indicate that realistic applications come into reach.

Choroidal Thickness in Open-angle Glaucoma.

PURPOSE: To examine choroidal thickness in open-angle glaucoma. METHODS: The hospital-based case series study included a study group with patients with open-angle glaucoma and a control group. Choroidal thickness was measured by enhanced depth imaging by spectral domain optical coherence tomography. RESULTS: The study group included 39 patients (71 eyes) and the control group consisted of 189 patients (228 eyes) with no significant difference between both groups in age (P=0.16) and refractive error (P=0.07). Choroidal thickness in the foveal region (P=0.18), at a distance of 1000 µm from the fovea (P=0.39), 2000 µm from the fovea (P=0.46), and 2500 µm from the fovea (P=0.53) did not vary significantly between both groups. In multivariable analysis with adjustment for age and refractive error, choroidal thickness at the fovea [P=0.12; regression coefficient B: minus-8.60; 95% confidence interval (CI): -19.3, 2.1], at a horizontal distance of 1000 µm from the fovea (P=0.30; regression coefficient B: -4.98; 95% CI: -14.3, 4.4), 2000 µm from the fovea (P=0.20; regression coefficient B: -20.9; 95% CI: -53.2, 11.3), and 2500 µm from the fovea (P=0.45; regression coefficient B: -2.70; 95% CI: -9.67, 4.27) was not significantly associated with the diagnosis of glaucoma. In binary regression analysis with adjustment for age and refractive error, presence of glaucoma was significantly associated neither with subfoveal choroidal thickness [P=0.12; odds ratio (OR): 0.997; 95% CI: 0.993, 1.001] nor with choroidal thickness at a horizontal distance of 1000 µm from the fovea (P=0.47; OR: 0.998; 95% CI: 0.993, 1.002), 2000 µm from the fovea (P=0.23; OR: 0.997; 95% CI: 0.993, 1.002), or 2500 µm from the fovea (P=0.46; OR: 0.998; 95% CI: 0.992, 1.004). CONCLUSIONS: After adjusting for age and refractive error, open-angle glaucoma was not significantly associated with a marked thinning or a thickening of the choroid in the foveal and parafoveal region.

Choroidal thickness in nonarteritic anterior ischemic optic neuropathy.

PURPOSE: To examine choroidal thickness in nonarteritic anterior ischemic optic neuropathy (AION). DESIGN: Retrospective case control study. METHODS: In the eye clinic of the University Medical Center in Mannheim, Germany, we studied a group that consisted of patients with nonarteritic AION and a control group that consisted of individuals with normal fundus. Choroidal thickness was measured by the enhanced-depth imaging of spectral-domain optical coherence tomography. The main outcome measure was choroidal thickness. RESULTS: The study group consisted of 20 patients: 11 patients with acute nonarteritic AION and an unaffected contralateral eye and 9 patients with acute unilateral nonarteritic AION and previously nonarteritic AION in the contralateral eye. The control group consisted of 58 patients (58 eyes). In multivariate analysis, thinner subfoveal choroidal thickness was associated with the diagnosis of nonarteritic AION (P = 0.001; regression coefficient B, -55.1), after adjusting for age (P < 0.001) and refractive error (P = 0.20). Similarly, unaffected eyes contralateral to eyes with acute nonarteritic AION as compared to control eyes showed thinner subfoveal choroidal thickness (P = 0.037) after adjusting for age (P = 0.001) and refractive error (P = 0.06). In a reverse manner, nonarteritic AION was associated with thinner subfoveal choroidal thickness (P = 0.007) after adjusting for age, optic disc diameter, gender, and refractive error. CONCLUSIONS: Eyes affected by nonarteritic AION and unaffected contralateral eyes showed significantly thinner macular choroids than eyes of a control group after adjusting ocular and systemic parameters. A thin choroid may be added to the diagnostic features of nonarteritic AION. Future studies may examine the pathophysiologic meaning of the finding.

Target refraction for best uncorrected distance and near vision in cataract surgery.

PURPOSE: To assess the target refractive error after cataract surgery to achieve best uncorrected visual acuity for both distance vision and reading vision. METHODS: The study included patients consecutively undergoing routine phacoemulsification with clear corneal incisions and implantation of a foldable monofocal intraocular lens (IOL). Uncorrected distance visual acuity (UCDVA), best-corrected distance visual acuity (BCDVA), uncorrected near visual acuity (UCNVA,) and best-corrected near visual acuity were measured at 93 ± 47 days (minimum 4 weeks) after surgery. Inclusion criteria were a postoperative cylindrical refractive error ≤1.5 D and an unremarkable postoperative status. RESULTS: The study included 493 eyes of 493 patients with a mean age of 74.2 ± 8.7 years and mean axial length 23.4 ± 1.1 mm. The UCDVA significantly (p<0.001) increased with decreasing myopic refractive error (spherical equivalent) towards emmetropia and then significantly (p<0.001) decreased with increasing hyperopic refractive error. The UCNVA significantly (p<0.001) decreased with decreasing myopic and increasing hyperopic refractive error. The ascending UCDVA line and the descending UCNVA line intersected in the refractive error range (spherical equivalent) of -1.00 D to -1.50 D. For patients with a BCDVA of ≥20/25, the lines of UCDVA and UCNVA intersected at a UCDVA range between 20/40 (logMAR 0.30; -1.5 D) and 20/32 (logMAR 0.26; -1.0 D) and at a UCNVA range between Jaeger 3 (logMAR 0.26) and Jaeger 4 (logMAR 0.32). CONCLUSIONS: For routine unilateral cataract surgery with implantation of monofocal IOLs, target refractive error to achieve best uncorrected distance and near vision was in the range of -1.00 D to -1.50 D (spherical equivalent).

Intravitreal low-dosage bevacizumab for retinopathy of prematurity.

PURPOSE: To report on the therapeutic effect of intravitreal low-dose bevacizumab for treatment for retinopathy of prematurity (ROP). METHODS: The single-centre retrospective, non-comparative case series study included all infants who consecutively underwent intravitreal injection of 0.375 mg bevacizumab (0.03 ml) under light sedation in topical anaesthesia as therapy of ROP in zone I or zone II. RESULTS: The clinical charts of 29 patients (57 eyes) with a median birth weight of 630 g (range: 290-1390 g) and median gestational age of 25 + 1 weeks (range: 23 + 1-30 weeks) were reviewed. Six children (12 eyes) were graded as ROP with zone I retinopathy and plus disease. The 23 remaining infants had extraretinal neovascularizations in zone II or partly zone I. The intravitreal bevacizumab injection was injected at a median age of 12 + 1 weeks (range: 7 + 4-21 + 4), the median follow-up was 4.2 months (range: from 3 days to 45.1 months). In all eyes treated, a regression of plus disease occurred within two to six days, retinal neovascularizations regressed within 2-3 weeks and pupillary rigidity improved. None except one child in exceptionally bad general health conditions needed a second intravitreal bevacizumab injection. In none of the infants, any ophthalmologic side-effects of the bevacizumab application were detected during the follow-up period. CONCLUSIONS: The intravitreal injection of a low dose of 0.375 mg bevacizumab showed a high efficacy as treatment for ROP. The question arises whether the low dosage of bevacizumab as compared to the dosage of 0.625 mg bevacizumab may be preferred.

Choroidal thickness in age-related macular degeneration.

PURPOSE: To examine choroidal thickness in age-related macular degeneration (AMD). METHODS: The hospital-based case series study included patients with nonexudative or exudative AMD as study group, and the control group consisted of subjects with a normal fundus. Choroidal thickness was measured by enhanced depth imaging of spectral domain optical coherence tomography. RESULTS: The study group (126 patients; 204 eyes) included a nonexudative subgroup (n = 50 eyes) and an exudative subgroup (n = 154 eyes), differentiated into eyes with mostly retinal pigment epithelium detachment (n = 35), mostly retinal edema (n = 36), and a subretinal fibrotic scar (n = 83). For 29 patients with unilateral AMD, contralateral normal eyes were compared with affected eyes. The control group consisted of 189 patients (228 eyes). Comparing choroidal thickness between the affected eyes and contralateral unaffected eyes in patients with unilateral AMD revealed no statistically significant differences (all P > 0.20). After adjusting for age and refractive error, subfoveal choroidal thickness was not significantly (all P > 0.10) related with AMD neither as a whole nor with the nonexudative or exudative AMD subgroup nor with the single exudative AMD subtypes (except for the subretinal fibrotic scar subgroup; P = 0.03). Correspondingly, choroidal thickness at a horizontal distance of 1000 µm from the fovea was not significantly (all P ≥ 0.30) associated with any subgroup of AMD. In binary regression analysis, the presence of AMD or of its subtypes (except for subretinal fibrotic scar type) was not significantly (all P ≥ 0.20) associated with subfoveal or parafoveal choroidal thickness after adjustment for age and refractive error. After matching for age, refractive error, and axial length, study group and control group did not differ significantly (all P ≥ 0.25) in foveal or parafoveal choroidal thickness measurements. CONCLUSION: After adjusting for age and refractive error, AMD, neither in its nonexudative form nor exudative form, was significantly associated with a marked thinning or thickening of the choroid in the foveal and parafoveal region.

Systems metabolic engineering of Corynebacterium glutamicum for production of the chemical chaperone ectoine.

BACKGROUND: The stabilizing and function-preserving effects of ectoines have attracted considerable biotechnological interest up to industrial scale processes for their production. These rely on the release of ectoines from high-salinity-cultivated microbial producer cells upon an osmotic down-shock in rather complex processor configurations. There is growing interest in uncoupling the production of ectoines from the typical conditions required for their synthesis, and instead design strains that naturally release ectoines into the medium without the need for osmotic changes, since the use of high-salinity media in the fermentation process imposes notable constraints on the costs, design, and durability of fermenter systems. RESULTS: Here, we used a Corynebacterium glutamicum strain as a cellular chassis to establish a microbial cell factory for the biotechnological production of ectoines. The implementation of a mutant aspartokinase enzyme ensured efficient supply of L-aspartate-beta-semialdehyde, the precursor for ectoine biosynthesis. We further engineered the genome of the basic C. glutamicum strain by integrating a codon-optimized synthetic ectABCD gene cluster under expressional control of the strong and constitutive C. glutamicum tuf promoter. The resulting recombinant strain produced ectoine and excreted it into the medium; however, lysine was still found as a by-product. Subsequent inactivation of the L-lysine exporter prevented the undesired excretion of lysine while ectoine was still exported. Using the streamlined cell factory, a fed-batch process was established that allowed the production of ectoine with an overall productivity of 6.7 g L(-1) day(-1) under growth conditions that did not rely on the use of high-salinity media. CONCLUSIONS: The present study describes the construction of a stable microbial cell factory for recombinant production of ectoine. We successfully applied metabolic engineering strategies to optimize its synthetic production in the industrial workhorse C. glutamicum and thereby paved the way for further improvements in ectoine yield and biotechnological process optimization.

Intravitreal bevacizumab for retinopathy of prematurity: refractive error results.

PURPOSE: To evaluate refractive error in infants who underwent intravitreal bevacizumab injection for treatment of threshold retinopathy of prematurity (ROP). DESIGN: Retrospective nonrandomized interventional comparative study. METHODS: The study group included all infants who consecutively received a single intravitreal bevacizumab (0.375 mg or 0.625 mg) injection for therapy of threshold ROP in fundus zone I or zone II. The control group included infants who had previously undergone retinal argon laser therapy of ROP. The follow-up examination included refractometry under cycloplegic conditions. RESULTS: The study group included 12 children (23 eyes; mean birth weight: 622 ± 153 g; gestational age: 25.2 ± 1.6 weeks) and the control group included 13 children (26 eyes; birth weight: 717 ± 197 g; gestational age: 25.3 ± 1.8 weeks). Both groups did not differ significantly in birth age and weight and follow-up. At the end of follow-up at 11.4 ± 2.3 months after birth, refractive error was less myopic in the study group than in the control group (-1.04 ± 4.24 diopters [median: 0 diopters] vs -4.41 ± 5.50 diopters [median: -5.50 diopters]; P = .02). Prevalence of moderate myopia (17% ± 8% vs 54% ± 10%; P = .02; OR: 0.18 [95% CI: 0.05, 0.68]) and high myopia (9% ± 6% vs 42% ± 10%; P = .01; OR: 0.13 [95% CI: 0.03, 0.67]) was significantly lower in the bevacizumab group. Refractive astigmatism was significantly lower in the study group (-1.0 ± 1.04 diopters vs 1.82 ± 1.41 diopters; P = .03). In multivariate analysis, myopic refractive error and astigmatism were significantly associated with laser therapy vs bevacizumab therapy (P = .04 and P = .02, respectively). CONCLUSIONS: In a 1-year follow-up, a single intravitreal bevacizumab injection as compared to conventional retinal laser coagulation was helpful for therapy of ROP and led to less myopization and less astigmatism.

Intravitreal bevacizumab for retinopathy of prematurity.

BACKGROUND: To evaluate the therapeutic effect of a single intravitreal injection of bevacizumab for treatment of threshold retinopathy in retinopathy of prematurity (ROP). METHODS: The retrospective study consisted of all infants who developed threshold ROP in fundus zone I or zone II and who consecutively received an intravitreal injection of bevacizumab (0.375 mg, 0.03 mL) in local anesthesia. RESULTS: Twelve infants (23 eyes) were included into the study. The mean birth weight was 625±187 g (mean±standard deviation; range: 450-810 g), mean gestational age was 25.1±1.4 weeks (range: 24.0-28.7 weeks), mean age at the time of intervention was 38.1±3.7 gestational weeks (range: 32.1-45.6 weeks), and mean follow-up was 30.4±25.9 weeks. Three children (6 eyes) showed aggressive posterior ROP. After the injection, all eyes showed a regression of plus disease within 2-6 days, a decrease in pupillary rigidity, a resolution of any tunica vasculosa lentis, and a complete regression of the retinal neovascularization within 2-3 weeks. In none of the children a second intravitreal injection of bevacizumab was performed. CONCLUSIONS: A single intravitreal bevacizumab injection of 0.375 mg in 0.03 mL appears to be potentially helpful for the therapy of threshold ROP avoiding side effects of conventional retinal laser coagulation such as irreversible retinal scarring. Long-term effects and side effects may be assessed in future prospective randomized trials.

Lens capsular bag irrigation for low-grade endophthalmitis.

PURPOSE: In postoperative low-grade endophthalmitis, microorganisms of low pathogenicity exhibit prolonged survival times by sequestration into the capsular bag. Thus, removal or irrigation of the capsular bag as nidus of the microorganisms is an essential therapeutic step. Correspondingly, guidelines suggest pars plana vitrectomy, capsulectomy and/or intraocular lens removal. Here, we report on capsular bag irrigation alone as an alternative, minimally invasive therapeutic method for postoperative infectious low-grade endophthalmitis. METHODS: Nine patients consecutively presenting with whitish precipitates in the capsular bag, anterior chamber inflammation and mild vitritis 2 weeks to 6 months following uncomplicated cataract surgery were included. Using an irrigation/aspiration cannula, synechiae were opened, the intraocular lens was rotated within the intact capsular bag and irrigated with 30 ml Ringer's solution containing 0.16 mg/ml gentamicin and 0.04 mg/ml vancomycin in topical anaesthesia. RESULTS: In all patients, the inflammation subsided within 2 days to 2 weeks. Visual acuity improved in all patients, mostly to post cataract surgery levels. Visual acuity remained stable during follow-up ranging from 2 to 39 months. No further interventions were required. CONCLUSIONS: The results suggest that capsular bag irrigation as first and single surgical step can be a useful, minimally invasive procedure in the surgical armamentarium for the treatment of infectious low-grade endophthalmitis. It may avoid removal of the intraocular lens and reduce the surgical risks of more complex procedures.

Visual acuity change after intravitreal bevacizumab for exudative age-related macular degeneration in relation to subfoveal membrane type.

PURPOSE: To examine an association between the subfoveal neovascular membrane type and visual acuity change after intravitreal bevacizumab injection for exudative age-related macular degeneration (AMD). METHODS: We carried out a clinical, retrospective, interventional case-series study including 66 consecutive patients (67 eyes) with exudative AMD who received an intravitreal injection of 1.5 mg bevacizumab. Study subgroups included the occult type without or with minimally classic subfoveal neovascularization (n = 28 eyes, 42%), predominantly or purely classic subfoveal neovascularization (n = 22 eyes, 33%), and eyes with retinal pigment epithelium detachment (n = 17 eyes, 25%). Follow-up was >or= 2 months. RESULTS: The maximal visual acuity (VA) gain (mean +/- standard deviation - 0.07 +/- 0.30 logMAR, 0.5 +/- 2.9 Snellen lines; p = 0.87), and VA gain at 1 month (p = 0.10), 2 months (p = 0.77) and 3 months (p = 0.35) after the injection did not vary significantly between the three study subgroups. Correspondingly, a multivariate analysis did not reveal a statistically significant (p = 0.57) influence of subfoveal lesion type on gain in VA. CONCLUSIONS: Visual improvement after intravitreal bevacizumab does not differ markedly between various types of subfoveal neovascularization in AMD.

Repeated intravitreal high-dosage injections of triamcinolone acetonide for diffuse diabetic macular edema.

OBJECTIVE: To report the results of repeated intravitreal injections of triamcinolone acetonide for treatment of diffuse diabetic macular edema. DESIGN: Retrospective interventional comparative study. PARTICIPANTS: The investigation included a study group (the responders) of 19 patients (22 eyes) with diffuse diabetic macular edema, who showed an improvement in visual acuity after an intravitreal injection of approximately 20 mg triamcinolone acetonide, and who received a second intravitreal injection 10.0+/-3.8 months after the first injection. A control group consisted of 31 patients with diffuse diabetic macular edema without treatment during follow-up. METHODS: Intravitreal injection of approximately 20 mg triamcinolone acetonide. MAIN OUTCOME MEASURES: Visual acuity and intraocular pressure. RESULTS: Follow-up after the second injection was 9.1+/-4.9 months. Four patients received a third injection at 9.7+/-3.7 months after the second injection, with a follow-up after the third injection that was at 7.9+/-11.5 months. After the second and third injections, visual acuity increased significantly (P = 0.002 and P = 0.068, respectively) by 1.8+/-2.1 and 4.0+/-2.6 Snellen lines, respectively. Eleven eyes (50%) showed an improvement in visual acuity by at least 2 Snellen lines after the second injection, and 3 patients (75%) experienced a gain in visual acuity by at least 2 Snellen lines after the third injection. Intraocular pressure increased significantly (P<0.01) after each injection, and returned to baseline values before each reinjection. Visual acuity improvement (P>0.05) and intraocular pressure rise did not differ significantly (P>0.55) between the various injections. Improvement in visual acuity and rise of intraocular pressure lasted approximately 6 to 8 months after each injection. CONCLUSIONS: Intravitreal injection of approximately 20 mg triamcinolone acetonide may repeatedly lead to an improvement in visual acuity and a rise of intraocular pressure in patients with diffuse diabetic macular edema. The duration of the effect after each injection is approximately 6 to 8 months. Tachyphylaxis in visual acuity or intraocular pressure outcomes were not observed.

Intereye difference in exudative age-related macular degeneration with minimally classic or occult subfoveal neovascularization after unilateral intravitreal injection of triamcinolone acetonide.

PURPOSE: To report on visual outcome after intravitreal injection of triamcinolone acetonide for exudative age-related macular degeneration. DESIGN: Interventional comparative non-randomized clinical trial. SETTING: Institutional. PATIENTS: Twenty consecutive patients with bilateral exudative age-related macular degeneration with minimally classic or occult subfoveal neovascularisation. INTERVENTIONS: Unilateral intravitreal injection of about 20 mg triamcinolone acetonide into the eye (study group) more severely affected or showing more pronounced progression of the disease. Mean follow-up was 13.5 +/- 4.1 months. MAIN OUTCOME MEASURES: Visual acuity. RESULTS: In the study group, visual acuity increased significantly (P < 0.001) from 0.96 +/- 0.32 logMar to a mean maximum of 0.76 +/- 0.30 logMar during follow-up. An increase in best visual acuity during follow-up was found in 18 (90%) eyes. In 11 (55%) eyes and 7 (35%) eyes, respectively, best visual acuity increased by at least two Snellen lines and three Snellen lines, respectively. In the control group, visual acuity at baseline and the highest visual acuity measurements during follow-up did not vary significantly (P = 0.90). Comparing study group and control group, visual acuity gain was significantly (P = 0.003) higher in the study group. Correspondingly, the number of eyes with an increase in visual acuity (P = 0.002) and with an increase in visual acuity higher > or = 3 lines compared to a loss of > or = 3 lines was significantly (P = 0.027) higher in the study group. CONCLUSIONS: Intravitreal triamcinolone acetonide may temporarily increase visual acuity in eyes with exudative age-related macular degeneration.

Inter-eye difference in diabetic macular edema after unilateral intravitreal injection of triamcinolone acetonide.

PURPOSE: To report on visual outcome of patients receiving intravitreal triamcinolone acetonide for treatment of diffuse diabetic macular edema. DESIGN: Prospective, comparative clinical interventional study. SETTING: Institutional. patient population: The study included 25 consecutive patients (50 eyes) with bilateral diabetic macular edema. Intervention procedure: Unilateral intravitreal injection of about 20 mg triamcinolone acetonide into the eye (study group) more severely affected by diabetic maculopathy. The contralateral eyes served as control group. Mean follow-up was 7.1 +/- 4.1 months. MAIN OUTCOME MEASURE: Visual acuity, intraocular pressure. RESULTS: In the study group, visual acuity increased significantly (P < or = .001) by 3.0 +/- 2.6 Snellen lines to a peak at two to six months after the injection, and decreased significantly (P = .001) towards the end of follow up. At the end of follow-up, visual acuity was higher, not significantly (P = .18) higher, than at baseline. An increase in visual acuity was found in 23 eyes (92%). In the control group, differences between visual acuity at baseline and at any of the re-examinations during follow-up were not significant (P > .10). In an intra-individual inter-eye comparison, gain in visual acuity was significantly (P < .05) higher in the injected eyes, for the measurements obtained up to four months after injection. CONCLUSIONS: Intravitreal triamcinolone acetonide may temporarily increase visual acuity in eyes with diabetic macular edema.