LRG1: an emerging player in disease pathogenesis.

The secreted glycoprotein leucine-rich α-2 glycoprotein 1 (LRG1) was first described as a key player in pathogenic ocular neovascularization almost a decade ago. Since then, an increasing number of publications have reported the involvement of LRG1 in multiple human conditions including cancer, diabetes, cardiovascular disease, neurological disease, and inflammatory disorders. The purpose of this review is to provide, for the first time, a comprehensive overview of the LRG1 literature considering its role in health and disease. Although LRG1 is constitutively expressed by hepatocytes and neutrophils, Lrg1-/- mice show no overt phenotypic abnormality suggesting that LRG1 is essentially redundant in development and homeostasis. However, emerging data are challenging this view by suggesting a novel role for LRG1 in innate immunity and preservation of tissue integrity. While our understanding of beneficial LRG1 functions in physiology remains limited, a consistent body of evidence shows that, in response to various inflammatory stimuli, LRG1 expression is induced and directly contributes to disease pathogenesis. Its potential role as a biomarker for the diagnosis, prognosis and monitoring of multiple conditions is widely discussed while dissecting the mechanisms underlying LRG1 pathogenic functions. Emphasis is given to the role that LRG1 plays as a vasculopathic factor where it disrupts the cellular interactions normally required for the formation and maintenance of mature vessels, thereby indirectly contributing to the establishment of a highly hypoxic and immunosuppressive microenvironment. In addition, LRG1 has also been reported to affect other cell types (including epithelial, immune, mesenchymal and cancer cells) mostly by modulating the TGFß signalling pathway in a context-dependent manner. Crucially, animal studies have shown that LRG1 inhibition, through gene deletion or a function-blocking antibody, is sufficient to attenuate disease progression. In view of this, and taking into consideration its role as an upstream modifier of TGFß signalling, LRG1 is suggested as a potentially important therapeutic target. While further investigations are needed to fill gaps in our current understanding of LRG1 function, the studies reviewed here confirm LRG1 as a pleiotropic and pathogenic signalling molecule providing a strong rationale for its use in the clinic as a biomarker and therapeutic target.

Factors affecting laser power in retinal Navilas laser treatment.

PURPOSE: To evaluate the effect of patient-associated factors on the minimum laser power needed for a mild visible burn in focal laser treatments using the 532 nm Navilas laser system. METHODS: We conducted a monocentric prospective pilot study of 58 eyes of 40 patients with diabetic macular edema. The following parameters were analysed: axial length, refraction, iris pigmentation, lens status, lens grading and densitometry, retinal and choroidal thickness and focus setting during treatment. Laser power was adjusted to produce mild, barely visible burns. Retinal laser burn size was measured 30 min after treatment. RESULTS: Focus setting is significantly correlated with retinal lesion size (r = 0.50, p = 0.001) and laser power (r = 0.44, p < 0.001). Axial length only correlated with laser power when the effect of focus was controlled. Phakic eyes needed more laser power than pseudophakic eyes (78.3 versus 67.2 mW, p = 0.051). No correlation of laser power with any other factor could be found. CONCLUSIONS: Among the examined parameters, focus setting had the strongest effect on the laser power needed to produce a mild visible burn. The association of focus with laser power can be explained by the focus-dependent change of retinal spot size. Lens status (phakic versus pseudophakic patients) seems to influence laser light transmission in the examined age group.

Light-emitting diode technology in vitreoretinal surgery.

BACKGROUND: Systems for vitreoretinal illumination during surgery usually consist of an external light source and a light fiber. We introduce a new illumination system for vitreoretinal surgery based on the light-emitting diode technology, with an embedded light source in the handle of the light fiber, making a separate light source unnecessary. METHODS: A prototype of a new illumination system for vitreoretinal surgery (ocuLED; Geuder, Heidelberg, Germany) was tested. This system consists of a handle with a built-in light-emitting diode, supported by an external power source. The OcuLED was analyzed in regards to wavelength, maximum radiant power, and maximum irradiance and was compared with three commercially available vitreoretinal illumination systems. Furthermore, the first intraoperative application and handling were evaluated. RESULTS: The ocuLED system works with a cool white or a neutral white light-emitting diode and is powered externally. The wavelength spectrum shows a maximum at 565 nm and a second peak at 455 nm. Compared with other light sources, the proportion of potentially harmful blue light is low. Maximum radiant power and irradiance are in line with xenon and mercury vapor light sources. The intrasurgical light is bright and offers good visibility. The handle of ocuLED is slightly wider than commonly used light fiber handles, which do not affect its use during surgery. CONCLUSION: Technical progress in light-emitting diode technology allows minimizing the equipment for vitreoretinal illumination. The OcuLED provides bright illumination without an external light source. Wavelength spectrum, maximum radiant power, and irradiance are safe from the risk of phototoxic damage. Intrasurgical handling is identical to conventional light fibers.

Intravitreal bevacizumab in vascular pigment epithelium detachment as a result of subfoveal occult choroidal neovascularization in age-related macular degeneration.

PURPOSE: The purpose of this study was to evaluate the effect of intravitreally administered bevacizumab on untreated vascularized pigment epithelium detachment (PED) in sub- or juxtafoveal occult choroidal neovascularization as a result of age-related macular degeneration. METHODS: In this retrospective study, 28 untreated eyes of 26 patients (4 men, 22 women; mean age, 74.6 ± 7.2 years) with PED and sub- or juxtafoveal occult choroidal neovascularization as a result of age-related macular degeneration and additional intra- and/or subretinal fluid were treated with intravitreal injections of 1.25 mg bevacizumab. Baseline and follow-up visits included best-corrected visual acuity, complete ophthalmic examination, and Stratus optical coherence tomography. Fluorescein angiography was performed at baseline. Reinjections were performed if intra- and/or subretinal fluid persisted or recurred or PED increased. RESULTS: Patients received 3.2 ± 1.8 injections (follow-up 37.9 ± 18.3 weeks). Mean maximum PED height showed a tendency to decrease (372 ± 150.5 µm to 290.3 ± 189 µm; P = 0.094). In 14 eyes (53.8%), PED height was reduced at last visit, including complete flattening in 1 eye. Mean visual acuity remained stable (0.58 ± 0.30 logarithm of the minimum angle of resolution to 0.58 ± 0.37 logarithm of the minimum angle of resolution; P = 0.905). Pigment epithelium detachment response to treatment did not correlate with baseline PED height or visual acuity at baseline or at the last visit. One patient sustained a retinal pigment epithelium rip, and another patient sustained an extensive subretinal hemorrhage. CONCLUSION: During bevacizumab therapy, mean PED height decreases in 50% of patients. No predictive factors for the response of PED to bevacizumab treatment could be identified. Treatment of PED with bevacizumab might result in a long-term functional benefit compared with the natural course.

Predictive factors for changes in macular edema in intravitreal bevacizumab therapy of retinal vein occlusion.

BACKGROUND: To evaluate prognostic factors of response to intravitreal bevacizumab therapy of macular edema (ME) due to central retinal vein occlusion (CRVO) or branch retinal vein occlusion (BRVO). METHODS: Patients with ME due to CRVO (32 patients) or BRVO (38 patients) received intravitreal bevacizumab (2.5 mg/0.1 ml) at baseline, and every 6 to 8 weeks if OCT showed persistent or recurrent ME. Visual acuity (EDTRS), ophthalmic examination and OCT were performed at baseline and at all follow-up visits. Six to 8 weeks after first injection, baseline factors (visual acuity, central retinal thickness, age and gender) were analyzed retrospectively between patients with resolved ME (group 1) and persisting ME (group 2). At last visit, baseline factors of patients with resolved ME since first injection (group A), with recurrent ME since baseline (group B) and with persistent ME since baseline (group C) were compared. RESULTS: In CRVO patients, central retinal thickness (CRT) and patients' age are prognostic predictors in bevacizumab therapy. Age of CRVO patients differed significantly between groups 1 and 2 after first injection, while CRT only showed a strong trend to thinner CRT. At last visit, age and CRT differed statistically significantly between groups A, B and C. In BRVO patients, none of the investigated factors revealed any prognostic value. In CRVO and BRVO patients, final CRT is correlated with the CRT after first injection. CONCLUSION: CRT and age of patients have prognostic value in bevacizumab therapy of ME due to CRVO. CRVO patients who benefit from therapy are significantly younger and have a lower CRT at baseline than patients with persisting ME. In BRVO patients, no predictive factors for effectiveness of bevacizumab therapy could be observed.

Long-term follow-up of OCT-guided bevacizumab treatment of macular edema due to retinal vein occlusion.

BACKGROUND: To evaluate the long-term outcome of an OCT-guided reinjection scheme for bevacizumab treatment of macular edema (ME) due to retinal vein occlusion. METHODS: Patients with persistent ME (>250 microm) due to central retinal vein occlusion (CRVO) or branch retinal vein occlusion (BRVO) received intravitreal bevacizumab 2.5 mg/0.1 ml. Visual acuity (ETDRS), ophthalmic examination and OCT were performed at baseline and at 6- to 8-week intervals. Reinjections were only performed if OCT showed persistent or recurrent ME. RESULTS: Sixty-one patients with a minimum follow-up of 25 weeks were included in this analysis. Mean follow-up was 60 +/- 29 wks. In CRVO patients, central retinal thickness (CRT) decreased from 748 +/- 265 microm to 372 +/- 224 microm (p < 0.001) and visual acuity (VA) improved by 1.9 +/- 3.2 lines. In BRVO patients, mean CRT decreased from 601 +/- 206 microm to 386 +/- 178 microm (p < 0.001) and VA improved by 1.8 +/- 2.6 lines. Thirty-three percent of CRVO and 15% of BRVO patients did not show a ME recurrence for > or =25 wks at last visit. Thirty-seven percent of CRVO and 50% of BRVO patients suffered recurrences of ME within the last 25 wks, whereas 30% of CRVO and 35% of BRVO patients did not achieve a complete resolution of ME at any follow-up visit after receiving a minimum of three injections. CRVO patients with dry interval of > or =25 weeks at last visit were significantly younger, had a thinner CRT at baseline and more often had a complete resolution of ME after the first injection. In CRVO and BRVO, final VA was correlated significantly with initial VA, patients' age and final CRT. Change of VA was correlated with change of CRT in BRVO. CONCLUSIONS: Patients with retinal vein occlusion benefit from treatment with bevacizumab. Favourable long-term results without necessity of further injections were achieved in 33% and 15% of CRVO and BRVO patients respectively. The remaining patients needed repeated injections to treat ME recurrences. However, one third of the CRVO/BRVO patients did not improve in VA, and further injections might be discontinued in these patients.

Intravitreal bevacizumab for treatment of chronic central serous chorioretinopathy.

PURPOSE: To evaluate the short-term safety and efficacy of intravitreal bevacizumab for the treatment of intraretinal or subretinal fluid accumulation secondary to chronic central serous chorioretinopathy (CSC). METHODS: Twelve patients were treated with intravitreal injections of 2.5 mg bevacizumab at 6- to 8-week intervals until intraretinal or subretinal fluid resolved. Observation procedures were Early Treatment Diabetic Retinopathy Study best-corrected visual acuity (BCVA), ophthalmic examination, and optical coherence tomography (OCT), performed at 6- to 8-week intervals. Fluorescein angiography was performed at baseline visit and thereafter depending on clinical and OCT findings. Multivariate analysis of variance with repeated measures was used to calculate a statistical significance of change in BCVA and mean central retinal thickness, which were the main outcome measures. SAS statistical software was used for analyses. RESULTS: Patients received 2-/+1 intravitreal injections of bevacizumab on average during a follow-up of 24-/+14 weeks. Mean BCVA increased by 2-/+2 lines; the change in BCVA (logMAR) was significant (p<0.02). Mean central retinal thickness decreased significantly over follow-up (p<0.05), with 6 patients (50%) showing complete resolution of subretinal fluid. CONCLUSIONS: Anatomic and functional improvement following intravitreal bevacizumab injections suggest that vascular endothelial growth factor (VEGF) may be involved in fluid leakage in patients with chronic CSC. The results suggest a possible role for anti-VEGF agents in the treatment of chronic CSC. Further evaluation of intravitreal bevacizumab for chronic CSC in controlled randomized studies is warranted.