bluuebunny/crossref_metadata_2025_split huggingface dataset:
VEGF/Ang‐2 imbalance: the crosslinking between methylglyoxal and vascular dysfunction in diabetic retinopathy
Authors: BENTO C , FERNANDES R , PEREIRA P 
Published: September 2008

Abstract Purpose Accumulation of methylglyoxal (MGO) in retinas of diabetic rats has been implicated in the formation of acellular capillaries, suggesting an important role for MGO in the vascular dysfunction observed in diabetes. In this study, we hypothesize that increased levels of MGO in retinal pigment epithelium (RPE) cells disturbs the balance VEGF/Ang2 secreted to the extracellular milieu, promoting apoptotis and low proliferation of endothelial cells. Methods ARPE19 cells were subjected both to hypoxia and MGO, two main features of diabetic retinopathy (DR). The levels of VEGF and Ang2 secreted into the culture medium were assessed by ELISA. Retinal endothelial cells were subsequently treated with the pre‐conditioned media of the ARPE19 cells, as well as with different ratios of VEGF and Ang2 recombinant proteins. Apoptotic cell death was determined by immunoblot against Bax and Bcl2, while endothelial cell proliferation was assessed by BrdU‐incorporation and fibrin gel angiogenic assays. Results MGO increases the levels of Ang2 and strongly decreases the levels of VEGF secreted by ARPE19 cells in response to hypoxia. VEGF downregulation appears to result from increased degradation of HIF1α and low HIF1 transcriptional activity. The VEGF/Ang2 imbalance generated by MGO significantly increases the expression of BAX and decreases the levels of Bcl2 of endothelial cells. Moreover, this imbalance also leads to decreased proliferation of the endothelial cells. Conclusion The VEGF/Ang2 imbalance induced by MGO activates the apoptotic cascade and induces low proliferation of retinal endothelial cells, possibly leading to vessels regression in pathologies that favour accumulation of MGO and where hypoxia is also present, such as DR.
Contribution of inflammation to the early stages of diabetic retinopathy
Authors: KERN T 
Published: September 2008

Abstract Purpose Many biochemical and physiological abnormalities detected in retinas of diabetic animals are consistent with a potential role of inflammatory‐like processes in the capillary degeneration. Methods We have used drugs and genetically modified rodents to investigate the role of inflammation in the development of early stages of diabetic retinopathy, focusing especially on the diabetes‐induced degeneration of retinal capillaries. Results In animal models, vascular lesions characteristic of the early stages of diabetic retinopathy have been found to be inhibited by salicylates (which inhibit NF‐κB and cyclooxygenase), a PARP inhibitor (which inhibits inflammatory responses apparently by regulating NF‐κB), minocycline (which inhibits the generation of IL‐1β), a topical inhibitor of cyclooxygenase, and by an inhibitor of iNOS. These studies demonstrate that inflammation plays a critical role in the development of early stages of diabetic retinopathy. Conclusion The concept that localized inflammatory processes play a role in the development of diabetic retinopathy is relatively new, but evidence that supports the hypothesis is accumulating rapidly. This new hypothesis offers new insight into the pathogenesis of diabetic retinopathy, and offers a novel target to inhibit the ocular disease.
New insights into the pathogenic role of advanced glycation in diabetic retinopathy
Authors: STITT AW 
Published: September 2008

Abstract Purpose Retinopathy is the most common microvascular complication of diabetes. The clinicopathology of microvascular lesions and neuroglial dysfunction in the diabetic retina have been extensively studied, although the relative contribution of various biochemical sequelae of hyperglycaemia remains ill‐defined. The formation and accumulation of advanced glycation endproducts (AGEs) is an important pathogenic pathway in the progression of diabetic retinopathy although some of the cellular and molecular pathologies initiated by these adducts in retinal cells remain unknown. Methods This presentation will cover several aspects of AGE‐linked retinal pathology and demonstrate opportunities for therapeutic intervention. The studies outlined will cover a wide range of molecular cell biology approaches using appropriate in vitro and in vivo model systems. Results It will be demonstrated that AGEs form in vivo in the diabetic retina through the reaction of alpha‐oxaloaldehydes leading to significant modifications of retinal proteins. Evidence will be presented to demonstrate that these AGEs act as significant effectors of retinal vascular and neuroglial cell dysfunction, leading to pro‐inflammatory responses, growth factor imbalance and, ultimately, neurovascular lesions such as blood retinal barrier dysfunction and microvascular degeneration. The protective role of novel AGE‐inhibitors will also be shown. Conclusion Evidence now points towards a pathogenic role for advanced glycation in the initiation and progression of diabetic retinopathy and this review lecture will outline the current state of knowledge of AGE‐related pathology in the retina at a cellular and molecular level.
Caspase‐1/interleukin‐1beta signaling in diabetic retinopathy
Authors: MOHR S 
Published: September 2008

Abstract Purpose The pro‐inflammatory cytokine, interleukin‐1β (IL‐1β), is known to induce vascular dysfunction and cell death. Previously, we have shown that caspase‐1 activity is increased in retinas of diabetic and galactosemic mice, and diabetic patients. Therefore, we investigated the role of IL‐1β and caspase‐1 (the enzyme that produces it) in diabetes‐induced degeneration of retinal capillaries. Methods First, we determined the effect of agents known to inhibit caspase‐1 (minocycline and tetracycline) on IL‐1β production and retinal capillary degeneration in diabetic and galactose‐fed mice. Diabetic and galactose‐fed mice were injected intraperitoneally with minocycline or tetracycline (5mg/kg). Second, we examined the effect of genetic deletion of the IL‐1β receptor on diabetes‐induced caspase activities and retinal capillary degeneration using IL‐1 receptor knock‐out mice. Results At 2 months of diabetes, minocycline inhibited hyperglycemia‐induced caspase‐1 activity and IL‐1β production in the retina. Long‐term administration of minocycline prevented retinal capillary degeneration in diabetic (6 months) and galactose‐fed (13 months) mice. Tetracycline inhibited hyperglycemia‐induced caspase‐1 activity in vitro, but not in vivo. Mice deficient in the IL‐1β receptor were protected from diabetes‐induced caspase activation and retinal pathology at 7 months of diabetes. Conclusion These results indicate that the caspase‐1/IL‐1β signaling pathway plays an important role in diabetes‐induced retinal pathology and its inhibition might represent a new strategy to inhibit capillary degeneration in diabetic retinopathy.
PARP, Na+/H+‐exchanger‐1, and early diabetes‐induced retinal changes
Authors: OBROSOVA IG 
Published: September 2008

Abstract Purpose To evaluate the roles for PARP and Na+/H+‐exchanger‐1 (NHE‐1) in early diabetes‐induced changes in the retina and retinal capillary cells Methods Control (C) and STZ‐diabetic (D) rats were treated with/without the PARP inhibitors, 1,5‐isoquinolinediol (ISO, 3 mgkg‐1d‐1 i.p.) or 10‐(4‐Methyl‐piperazin‐1‐ylmethyl)‐2H‐7‐oxa‐1,2‐diaza‐benzo[de]‐anthracen‐3‐one (GPI 15427, 30 mgkg‐1d‐1), for 10 wks after 2 wks without treatment. Apoptosis was evaluated in flat‐mounted retinas by TUNEL assay, and nitrotyrosine (NT), poly(ADP‐ribose) (PAR), GFAP, BiP/GRP78 and GRP94 expressions by immunohistochemistry and Western blot analyses. Primary bovine retinal pericytes and endothelial cells were cultured with/without 0.6 mM palmitate, or in 5 mM or 30 mM glucose. Apoptosis was assessed by TUNEL and caspase‐3 assays, superoxide production by ethidium fluorescence, and NT and PAR by immunocytochemistry. Results In the PARP study, the number of TUNEL‐positive nuclei was increased ~4‐fold in D, and this increase was prevented in D+ISO and D+GPI 15427. PARP inhibitors counteracted oxidative‐nitrosative and endoplasmic reticulum stresses, and glial activation. Palmitate dose dependently increased superoxide production in cultured retinal cells. GPI 15427, 20 microM, prevented FFA‐induced increase in the rate of apoptosis, and alleviated NT and PAR accumulation in both pericytes and endothelial cells. In the NHE‐1 study, the specific NHE‐1 inhibitor cariporide (10 microM) prevented high glucose‐induced apoptosis, and alleviated oxidative‐nitrosative stress and PAR accumulation in bovine retinal pericytes. In vivo studies in the STZ‐diabetic rat model are in progress. Conclusion PARP and NHE‐1 play an important role in early diabetes‐induced changes in retina and retinal capillary cells.
The role of gamma‐interferon tests for suspected tuberculous ocular inflammation
Authors: CIMINO L , LOSI M , RICHELDI L , BOIARDI L , CAPPUCCINI L , SALVARANI C 
Published: September 2008

Abstract Purpose To evaluate the introduction of new T‐cell based blood tests for tuberculosis infection in order to improve the diagnosis of ocular tuberculosis. Methods Patients with presumed ocular tuberculosis from the Ocular Immunology Unit of the hospital of Reggio Emilia underwent both Mantoux skin tests and Gamma Interferon assays to confirm the diagnosis of tuberculosis. Results 8 patients (7/8 male; mean age 58 yrs) were diagnosed with presumed ocular tuberculosis. Three patients presented with serpiginous retinochoroiditis and five with bilateral panuveitis. Four patients had undergone immunosuppressive therapy before the correct diagnosis was made. All the patients were positive both with Mantoux skin test and Gamma Interferon assays (ELISpot and QuantiFERON TB‐Gold). They started the specific anti‐tuberculous tritherapy, improving significantly in visual acuity and decreasing intraocular inflammation. Conclusion These results confirm the feasibility of these new blood tests in routine clinical work‐up. These new methods are important for the ophthalmologist in order to follow and evaluate developments in every method of detection of tuberculosis for the containment of this global public health epidemic.
The role of interferon alpha in uveitis therapy
Authors: BODAGHI B , GUEUDRY J , TERRADA C , CASSOUX N , PIETTE JC , LEHOANG P 
Published: September 2008

Abstract Purpose Severe uveitis is potentially associated with visual impairment or blindness in young patients. Therapeutic strategies remain controversial. Efficacy of interferon alpha‐2a (IFN‐a2a) in severe uveitis, refractory to steroids and conventional immunosuppressive agents has been evaluated. Methods Patients were included after a major relapse of uveitis occurring under corticosteroids and immunosuppressants. IFN‐a2a (3 millions units three times a week) was administered subcutaneously. Efficacy was assessed by the improvement of VA, decrease of vitreous haze, resolution of retinal vasculitis and macular edema, and decrease of oral prednisone threshold. Results Forty‐five patients were included. Mean age was 30.6 years (range 8‐58 years) and sex ratio (F/M) was 0.66. Uveitis was associated with Behçet’s disease in 23 cases (51.1%) and with other entities in 22 cases (48.9%). Mean duration of uveitis before interferon therapy was 50.5 months and an average of 3 relapses under corticosteroids and immunosuppressants has been noted. Uveitis was controlled in 82.6% of patients with BD and 59% of patients with other types of uveitis (p=0.07). During a mean follow‐up of 29.6 months, mean oral prednisone threshold decreased significantly from 21.5 mg/d to 9.8 mg/d (p<0.001). Interferon has been discontinued in 10 patients (22.2%) with BD and 4 patients without BD. Relapses occurred in 4 and 1 cases, respectively. Conclusion Though our study carries several limitations, interferon‐therapy seems an efficient strategy in severe and relapsing forms of BD but also other uveitic entities. However, it seems more suspensive than curative. Therefore, IFN‐α2a may be proposed as a second line strategy after the failure of conventional immunosuppressants.
Evolution of the laser treatment of diabetic retinopathy (DR): from laser surgery to laser therapy
Authors: DORIN G , BUZAWA D , MERCEREAU J 
Published: September 2008

Abstract Purpose To review benefits and collateral effects of conventional photocoagulation, the standard of care for DR, in comparison with newer laser techniques reported to provide comparable benefits with reduced treatment’s hardship and side effects. Methods Literature review and physical/technical considerations. Results Conventional photocoagulation lowers the risk of severe visual loss, but is associated with long, painful, multiple treatments and with iatrogenic anatomical and functional damage. Light panretinal photocoagulation (PRP) has shown efficacy similar to that of conventional PRP with fewer sessions and complications. A patterned scanning laser (PASCAL) allows PRP with reduced surgeon’s time, in 1 or 2 sessions, but still with discomfort and anatomical‐functional damages due to the visible "burn" endpoint. Conversely, subthreshold diode‐laser micropulse (SDM) PRP is a new laser therapy that comparably reduces the incidence of vitreous hemorrhage and vitrectomy with a gentle well tolerated treatment that does not cause iatrogenic vision deterioration or laser‐lesions detectable at any time postoperatively. Conclusion Retinal destruction has never been demonstrated to be a prerequisite for the therapeutic benefits. Whatever the elusive mechanisms of action of laser photocoagulation are, long term benefits can be provided either with high intensity/low density laser surgery or with low intensity/high density laser therapy. Non‐laser treatments for DR are being tested, often with good, rapid, but also only transient effects. The combination of pharmacotherapy's short term beneficial effects with the long term benefits of a less damaging laser therapy appears as a new treatment paradigm that should undergo rigorous investigation.
Commercial interest
Corneal keratocyte density after mechanical versus femtosecond laser in situ keratomileusis
Authors: CANADAS SUAREZ P , ARRANZ E , GIL‐CAZORLA R , TEUS M 
Published: September 2008

Abstract Purpose To determine changes in keratocyte density three months after mechanical versus femtosecond laser in situ keratomileusis. Methods This was a retrospective study in which 20 consecutive eyes received LASIK to correct a mean refractive error of ‐2,3+/‐2,1 D sphere and ‐0,8+/‐2,1 D cylinder, and 21 consecutive eyes received femtosecond laser to correct a mean refractive error of ‐1,8+/‐3,5 D sphere and ‐2,2+/‐2,9 D cylinder. Both groups were compared with a control group of 20 normal and healthy eyes with a mean refractive error ‐2,2+/‐2,9 D sphere and ‐0,5+/‐0,6 D cylinder. Corneas were examined by using confocal microscopy three months after the procedures. Keratocyte densities were determined in the anterior stroma, stromal bed, central and posterior stroma. Results Keratocyte density in the anterior stroma and in the stromal bed was 500,8 +/‐ 108,4 cells/mm2 in the control group, 506,1 +/‐ 130,6 cells/mm2 and 475,9 +/‐ 147 cells/mm2 respectively in the LASIK group, and 446 +/‐ 120,7 cells/mm2 and 416,3 +/‐ 115 cells/mm2 respectively in the femtosecond group (p>0,05). In central and posterior stroma the difference was also not significant. Conclusion Keratocyte density is decreased in the stromal bed after mechanical and femtosecond laser in situ keratomileusis as compared to controls, however, there is not difference between both procedures.
Effectiveness of moisturizing daily disposable lenses with additives
Authors: GILES TG 
Published: September 2008

Abstract Purpose Recently, contact lens manfacturers are incorporating moisture additives in their contact lenses. Examples include povidone in 1‐DAY ACUVUE MOIST lenses, polyvinyl alcohol (PVA) in DAILIES with AquaComfort lenses and hydroxypropyl‐methylcellulose, polyethylene‐glycol and PVA in the DAILIES AquaComfort Plus lenses. These two trials were aimed to compare the effectiveness of these additives to general lens performance. Methods In the first trial, 20 investigators in the US and Germany enrolled 276 subjects currently wearing nelfilcon A with PVA (nefA+1) lenses in daily disposable modality of comparison to nelfilcon A with moisturizing additives (HPMC, PEG and PVA (nefA+3) for ten days. In the second trial, 14 investigators in Germany enrolled 314 current daily disposable wearers to wear nelfilcon A with moisturizing additives HPMC, PEG and PVA (nefA+3), and etafilcon A with added PVP (etaA+1) for one week each. Results 273 subjects completed the first trial. Comfort upon insertion was rated 9.1 for nelfilcon A with moisturizing additives (nefA+3) and 8.7 for nelfilcon A lenses (nefA+1); comfort during the day was 8.7 and 8.7, respectively; end of day comfort was 7.9 and 7.2, respectively; overall comfort was 8.6 and 8.4, respectively. 309 subjects completed the second trial. Comfort upon insertion was rated 8.6 for nefA+3 and 7.6 for etaA+1; comfort during the day was 8.4 and 7.8, respectively; end of day comfort was 7.2 and 6.6, respectively; overall comfort was 8.4 and 7.5, respectively. Conclusion Mean comfort ratings were significantly in favor of nelfilcon A with additives HPMC, PEG and PVA in both trials. Future innovations in daily disposable lenses with added moisturizes to last throughout the day should be expected.
Commercial interest
Refractive surgery using CustomVis Solid State Laser 213nm. One year post‐op clinical evaluation supported by an experimental study
Authors: PALLIKARIS IG 
Published: September 2008

Abstract Purpose To report our experimental and clinical findings using a solid state laser system 213nm in refractive surgery. Methods 40 pigmented rabbits underwent myopic PRK using a solid state laser in one eye and excimer laser in the fellow eye. Rabbits were sacrificed immediately after the ablation, at 7days and at one, 3 and 12months after surgery. Corneal tissue was preserved for Light, Scan and Transmission electron microscopy. 60 patients (115eyes) underwent PRK [mSEQ ‐4.43±1.81D] and 20 patients (40eyes) LASIK [mSEQ ‐5.55±1.52D] using CustomVis quintupled Nd:YAG Solid State laser at 213nm. Results Experimental study: Immediately after the ablation, LM, scan and TEM microscopy revealed relatively smooth ablation surfaces in both groups. At 1,3 and 12m postoperatively, there was tissue appearance, typical for post‐PRK samples, of all corneal layers in both groups. Clinical study: At one year follow‐up for the PRK mRSEQ was ‐0.11±0.52D and mUCVA was 1.03. 39% gained more than 1 line, 48% had no loss or gain of lines and 12% lost more than 1 line. For the LASIK group at 12m the mRSEQ was 0.42±0.70D and the mUCVA was 0.94; 61% of eyes gained more than 1 line, 33.3% of eyes gained had no loss of lines and 5.6% of eyes lost more than 1 line. 67% of eyes were in the +/‐ 0.25 and 72% of eyes were in the +/‐0.5 interval for the Lasik patients. For the PRK patients 49% of eyes were in the +/‐ 0.25 and 80% of eyes were in the +/‐0.5 interval for the Lasik patients. Conclusion Photorefractive keratectomy in rabbits with ultraviolet solid state and excimer laser revealed similar histopathological findings up to one year postoperatively. PRK and LASIK were both effective and safe in the correction of myopic astigmatism.
Intracorneal lenses for the treatment of presbyopia: visual outcomes and safety
Authors: PALLIKARIS IG , BOUZOUKIS DI , KYMIONIS GD , PANAGOPOULOU S , PALLIKARIS AI 
Published: September 2008

Abstract Purpose To investigate the visual outcomes and safety of Intracorneal lenses (Invue Lens, Biovision AG, Switzerland) for the treatment of presbyopia. Methods This was a prospective clinical study. An intrastromal corneal tunnel was created using a microkeratome composed by a control unit, a suction ring and a cartridge. The lens was inserted within the cornea tunnel of the non‐dominant eye of 45 presbiopian patients. Mean age was 52,33 years old ± 3,29 (25 males and 20 females). The follow‐up was up to 12 months. Results In the operated eye, mean uncorrected visual acuity for distance (UVA‐D) preoperatively, one day, one week one month, three months,six months and 1 year after surgery was 20/20, 20/40, 20/40, 20/32, 20/32, 20/32 and 20/32 respectively, whereas for near (UVA‐N) was 20/50, 20/40, 20/30, 20/30, 20/25, 20/25 and 20/30.Binocular far vision was not altered.Contrast sensitivity tests demonstrated a decrease in scotopic and mesopic conditions.Wavefront analysis demonstrated an increase in all high order aberrations, whereas maximum myopic effect was demonstrated in 3,5 mm zone,which corresponded in the diameter of the lens. No tissue alterations of the cornea were found using corneal confocal microscopy. No intra or post‐operative complications were demonstrated up to one year after surgery. Conclusion Intracorneal lenses for presbyopia seems to be a safe and effective method to correct presbyopia in patients aged between 45 to 55 years old; a target group which is considered too old for refractive laser surgery and too young for clear lens extraction. Longer follow‐up and a larger population are necessary in order to draw more significant results of this new surgical approach for the treatment of presbyopia.
Multifocality and focus shift IOLs ‐ theoretical aspects
Authors: HULL CC 
Published: September 2008

Abstract Purpose The purpose of this talk is to review the clinically relevant optical properties of multifocal and accommodative intraocular lenses and the potential visual consequences. The intention is to develop a fundamental understanding for clinicians and those working with them. Methods Critical evaluation of the optical, clinical and vision science literature. Topics covered will include principles of refractive and diffractive lenses, apodization, effect of pupil size, compromises in design, single and dual optic accommodative intraocular lenses, objective and subjective accommodation, depth of focus and theories of accommodation. Results Design of multifocal lenses involves a compromise in image quality that does not always manifest itself visually but can be measured optically. Accommodative intraocular lenses are limited in the amount of accommodation they can restore by the longitudinal shift in the lens and also post operative changes in the capsule. Changes in the radii of curvature of the lens surfaces are much more efficient at producing alterations in lens power. Conclusion All surgeons and associated workers need a knowledge of the optical principles of multifocal and accommodative intraocular lenses together with their visual consequences if they are to understand the cause of unwanted side effects. In addition, they will be better equipped to understand new developments in this rapidly changing field.
Visiogen Synchrony dual‐optic lens
Authors: AUFFARTH GU 
Published: September 2008

Abstract Purpose Currently available single optic accommodative IOLs have their limitatations in terms of maximal potential accommodative amplitudes. A dual optic system may theoretically have more accommodative power. Methods The dual optic accommodative IOL Synchrony from the Company Visiogen (Irvine, Ca, USA) consists of a +30diopters anterior lens and a minus‐lens of variable power (depending on emmetropisation). The IOL is made of silicone material. Results Since more than 3 years this IOL is already under clinical investigation showing promising results. The lens has been implanted in several hundred patients in Europe and South America. A FDA study is currently running, in Europe the IOL is CE‐marked Accommodative values around 1‐4 dioptes have been measured and documented in patients. Conclusion Longterm results indicate low posterior capsule opacification and stable accommodative abilities.