bluuebunny/crossref_metadata_2025 huggingface dataset:
Expression of tissue inhibitors of matrix metalloproteinases 1 and 2 in corneal epithelium after UV irradiation
Authors: ARDAN T , CEJKOVA J
Published: November 2010

Purpose Tissue inhibitors of metalloproteinases (TIMPs) are capable of inhibiting the activities of all known matrix metalloproteinases (MMPs) and therefore they play a key role in maintaining the balance between synthesis and degradation of basic extracellular matrix components (collagens, glycosaminoglycans) in the normal cornea. However, under pathological conditions, disruption of this balance may appear due to the increased expression of MMPs or decreased expression of TIMPs. Purpose of this study was to investigate whether changes in expression of TIMPs might contribute to increased proteolytic activity of MMPs in corneas irradiated by UV rays.

Methods In the first group of rabbits the corneas were irradiated with UVA lamp (365 nm, once a day during 4 days, a dose per day 1.01 J/cm2), in the second group with UVB lamp (312 nm, once a day during 4 days, a dose per day 1.01 J/cm2). Normal corneas served as controls. TIMP‐1 and TIMP‐2 were examined in cryostat sections immunohistochemically using mouse monoclonal anti‐TIMP‐1 and anti‐TIMP‐2 antibodies.

Results Immunohistochemical examination showed that UVA rays did not change the expression of TIMPs studied in the corneal epithelium. In contrast, UVB rays induced the decreased expression of TIMPs in corneal epithelial cells. From both enzymes investigated in UVB irradiated corneas the decrease of TIMP‐1 expression was more significant than expression of TIMP‐2.

Conclusion Even if further studies are necessary, our results point to the suggestions that insufficient inhibition of MMPs due to the decreased presence of TIMPs in corneas irradiated by UVB rays may lead to corneal damage from excessive proteolytic degradation of corneal proteins.
Can peroperative bevacizumab (AvastinTM) improve trabeculectomy outcome? A prospective, randomized, placebo‐controlled study
Authors: VANDEWALLE E , ZEYEN T , SPIELBERG L , STALMANS I
Published: November 2010

Purpose Glaucoma surgery fails in 30% due to excessive scar formation of the constructed channel. Our group found that vascular endothelial growth factor (VEGF) is upregulated in the aqueous humor of glaucoma patients and postoperatively in a rabbit model for trabeculectomy, that VEGF stimulates fibroblast proliferation in vitro whereas bevacizumab can inhibit their growth, and that a single peroperative intracameral injection of bevacizumab improves the surgical outcome of trabeculectomy in a rabbit model. Based on these findings, we set up a clinical trial to study the potential of bevacizumab as an anti‐scarring agent after trabeculectomy.

Methods This is a prospective, randomized, placebo‐controlled, double‐blinded experimental study. The effect of peroperative administration of 50 µl of bevacizumab (25mg/ml) on intraocular pressure, bleb characteristics, as well as number of postoperative IOP‐lowering medications and surgical interventions is investigated. Patients with primary open‐angle glaucoma (POAG) and normal tension glaucoma (NTG) who are scheduled for primary trabeculectomy are included.

Results Inclusions started on April 2009 and are still ongoing. Based on a priori calculations we need to include 124 patients. We already included 97 patients, 54 of which are POAG and 43 are NTG patients. By the end of September the majority will have ended the study. The preliminary results of this group will be presented at EVER.

Conclusion This study will provide evidence on effectiveness and safety of single administration of bevacizumab during trabeculectomy to reduce the risk of surgical failure, avoiding or reducing the need for long‐term medication use or secondary surgical intervention.
Lowering IOP effect, expression of MMP2 in aqueous humour and in trabeculum after pneumotrabeculoplasty in rabbits
Authors: QUINTYN JC , MASSOUDI D , BUHANNIC L , MALECAZE F , GALLIACY S
Published: November 2010

Purpose To assess changes in metalloproteinases (MMP‐2) following pneumotrabeculoplasty in rabbits.

Methods Ten New‐Zeland Rabbits were used, 6 for the experiment and 4 for the control group. For the experimental group, the rabbits underwent a single PNT treatment on the both eyes on day 0 (baseline) and after 7 days. The combination of a PNT vacuum application of 60 seconds and a 5 minutes rest period followed by another PNT application constituted a single PNT treatment. All rabbits underwent an intraocular pression before treatment and each week. The whole sample was followed for 21 days. The gelatinolytic activity was analysed by gelatine zymography. This protocol performed twice.

Results The intraocular presssion was significantly lower in the experimental group (p< 0.01) at 2 and 3 weeks for the two experiments. Results on gelatinolytic activities, corresponding to pro MMP2, the active form of MMP2 and MMP9, where not clear‐cut. While the first treated group (6 eyes) results show an increase of activity, with a top of activity at day 21, the second experimentation (6 eyes) did not show modification of gelatinolytic activities. Additional studies are required to clarify this point.

Conclusion This study confirms the potential of PNT to lower IOP. Additional studies are required to clarify if MMP2 and MMP9 play a role in this reduction, or if the process involves different proteins.
Surgical outcomes of uveitic glaucoma
Authors: CARRENO E , PORTERO A , VILLARON S , HERRERAS JM , MAQUET JA , CALONGE M
Published: November 2010

Purpose Secondary glaucoma is a difficult and frequent complication of uveitis. The aim of this study is to describe the results of surgery in uveitic glaucoma.

Methods Retrospective observational study. Clinical and surgical data from 27 cases of uveitic glaucoma that underwent glaucoma surgery over a period of 9 years were collected.

Results The main diagnosis and etiology were anterior uveitis (66.7%) and herpes (33.3%) respectively. Trabeculectomy with mitomycin C was performed in 51.9% of the cases. An intraocular pressure lower than 16 mmHg and managed with less than two drugs was achieved in 48.15% of the cases. Higher risks of surgical failure were associated with intermediate uveitis, idiopathic uveitis, Fuchs’ heterochromic cyclitis, combined surgery with phacoemulsification, omission of mitomycin C, intraocular inflammation at surgery, and short time to glaucoma diagnosis and to surgery.

Conclusion These results should be taken into account to improve surgical outcome in uveitic glaucoma.
Time duration between « in » and « out » signal peaks of the ocular response analyser in normal and keratoconic eyes.
Authors: DELBARRE M , VERRET C , AGBOTON G , BULLET J , BLAVIER B , LEDUC C , CREPY P , FROUSSART‐MAILLE F , RIGAL‐SASTOURNE JC
Published: November 2010

Purpose Compare time duration between « in » and « out » signal peaks extracted from the signal curves of the ocular response analyser (ORA; Reichert Ophthalmic Instruments, Buffalo, NY, USA) in keratoconic eyes and in a control group without keratoconus.

Methods This retrospective, comparative case series comprised 23 patients with keratoconus and 54 age‐ and sex‐ matched controls who underwent a complete clinical eye examination, corneal topography, and biomechanical evaluation. Corneal hysteresis (CH), corneal resistance factor (CRF), and time duration between « in » and « out » signal peaks were compared between the two groups. Every patient was subjected to examination (between 3 and 5/per eyes) by the ORA.

Results Corneal hysteresis was 8.58+/‐ 1,82 mmHg (range: 5.21 to 17.1 mmHg) in the keratoconus group and 10.54+/‐ 1,81mmHg (range: 2.7 to 22.1 mmHg) in the control group (P<0,001 ). Corneal resistance factor was 7.59+/‐ 2,06 mmHg (range: 4.1 to 15.1 mmHg) in the keratoconus group and 10.6 +/‐ 2,03 mmHg (range: 4.10 to 23.70 mmHg) in the control group (P<0,001). Time duration between « in » and « out » signal peaks was 11.36+/‐ 0,70 ms (range: 9.9 to 14,5 ms) in the keratoconus group and 10.82+/‐ 0,51 ms (range: 8.7 to 12.6 ms) in the control group (P<0,001).

Conclusion Corneal hysteresis and corneal resistance factor were statistically lower in the keratoconus group compared with the control group as it was already showned in former studies. Time duration between “in” and “out” signal peaks is statistically significantly higher in the keratoconus group. This measure could be used in the evaluation of corneal biomechanical properties.
Microbial keratitis secondary to cosmetic contact lenses wear: a foreseeable disaster
Authors: SAUER A , FRENCH STUDY GROUP FOR CONTACT LENSES RELATED MICROBIAL KERA X , BOURCIER T
Published: November 2010

Purpose The aim of our study is to illustrate the implications of the cosmetic contact lenses (CCL) on ocular surface health and the occurence of microbial keratitis (MK).

Methods A prospective multicenter study was conducted in 10 French University Hospitals on all non‐cosmetic CL wearers presenting with MK (CLRMK) between July 2007 and July 2009, including CCL wearers, and on healthy CL wearers. Cases and healthy wearers were interviewed by a 50 items anonymous standardized "questionnaire" to determine subject demographics and CL wear history.

Results Two hundred fifty six patients were included for CLRMK. Thirty‐two of them (12.5%) were seen for MK after wearing CCL. One hundred thirteen healthy CL wearers were surveyed. Compared with healthy wearers, the relative risk of CL related MK is highly increased with CCL (OR, 16.5). Compared with CLRMK, CCL wearers are younger (21 versus 27 years of age) and recent CL wearers (3 versus 9 years). CCL were rarely dispensed by eye care professionals increasing the risk of MK (OR, 12.3). Education about lens care and handling was deficient (OR, 26.5). MK were more severe in the CCL wearers as compared as others CLRMK patients, with a high prevalence of gram negative bacillus and acanthamoeba keratitis.

Conclusion Patients who acquire CCL are less likely to be instructed on appropriate lense use. Consequently, CCL wearers are experiencing acute vision‐threatening infections.
Assessment of environmental AMD risk factors in a population of patients suffering from stroke and myocardial infarction
Authors: CREUZOT C , NICOT F , DUGAS B , ACAR N , BRETILLON L , BRON AM
Published: November 2010

Purpose Stroke and myocardial infarction are common diseases occurring in patients suffering from Age Macular Degeneration (AMD). We assessed the rate of AMD and AMD risk factors in patients suffering from recent stroke or myocardial infarction.

Methods Patients suffering from a recent stroke or myocardial infarction (less than 1 month) benefited from a thorough ophthalmic examination with the following measurements and evaluations: visual acuity, intraocular pressure, fundus photography, Raman spectroscopy and macular OCT. In the same time a food questionnaire was dispensed. Finally, blood samples to measure fatty acids and lutein were performed.

Results 74 patients were examined, 31 females and 43 males. The age of the patients was 65 ±10 years, [47‐90]. The rates of stage 2 and 3 AMD were 25.7 % and 13.5 % respectively (n=19, n=10). Raman spectroscopy did not differ between groups, p=0.83. Central retina thickness was increased in the AMD group, 250±37 µ versus 222±35 µ, p=0.04. The fatty acid profile and lutein in blood did not differ between patients with or without AMD, p=0.7 and p=0.21, respectively. The overall omega 6/ omega 3 ratio was 4.64 ± 0.97 in our population.

Conclusion The rate of AMD risk factors does not seem to be increased in the patients suffering from AMD in this population of patients suffering from stroke and myocardial infarction. A longitudinal study is needed to confirm these results.
Effect of lutein supplementation on macular pigment optical density in patients with AMD
Authors: KAYA S , WEIGERT G , PEMP B , SACU S , GARHOFER G , SCHMIDT‐ERFURTH U , SCHMETTERER L
Published: November 2010

Purpose Reduced macular pigment optical density (MPOD) and reduced lutein/zeaxanthin intake have been shown to be associated with age‐related macular degeneration (AMD). As such supplementation with lutein has been suggested as a therapeutic option in AMD. In the present study we hypothesized that lutein supplementation may improve MPOD in AMD patients.

Methods This hypothesis was tested in a randomized, double‐masked, placebo‐controlled parallel group study in patients with AMD with a 6 months study period. The randomization of lutein (20mg daily months 1‐3, 10 mg daily months 4‐6) versus placebo was 2:1. 126 patients with nonexudative AMD were included in this trial. Study visits were scheduled at baseline and 1 month, 3 months and 6 months after start of lutein or placebo intake. MPOD was measured with a custom built optical reflectometer based on a model of light propagation in the human retina. Statistical analysis was assessed using a repeated measures ANOVA model.

Results 104 patients finished the study as scheduled. Eight patients only showed up for the baseline visit and were not included in the analysis. In the remaining 14 patients who did not finish the trial the last observation was carried forward. Supplementation with lutein induced a highly significant increase in MOPD (p < 0.001 versus placebo). In the lutein group MPOD was 0.35 ± 0.02 at baseline and 0.43 ± 0.02 after 6 months of supplementation.

Conclusion These data indicate that supplementation with lutein improves MPOD in AMD patients. Given that reduced MPOD is a risk factor for AMD these data suggest that supplementation with lutein is beneficial in AMD.
Triple therapy for the treatment of choroidal neovascularization with pigment epithelium detachment in age‐related macular degeneration
Authors: QUINTYN JC
Published: November 2010

Purpose To investigate the effect of a triple therapy associating sub‐cunjonctival Triamcinolone acetonide, intravitreous Ranibizumab and photodynamic therapy for treatment of retinal pigment epithelium detachment complicating occult choroidal neovascularization in age‐related macular degeneration.

Methods A prospective clinical trial including 30 patients showing retinal pigment epithelium detachment. We treated these patients with intravitreous Ranibizumab injections and sub‐conjuctival Triamcinolone injections as well as a single session of photodynamic therapy at 48 h. At least two more intravitreous Ranibizumab injections were added at 1‐month intervals.

Results Initial visual acuity was 20/100 and 20/60 at 9 months, which was minimal follow‐up. Twenty‐five patients had total resumption of retinal pigment epithelium detachment on optical coherence tomography imaging after 1 month. One patient had ocular hypertension and we cut conjonctiva to remove Triamcinolone. After three days the patients had a normal intraocular pression. One had a pigment epithelium break but with good functional results. Ten patients needed six intravitreous injections of Ranibizumab with partial or total resumption in six cases.

Conclusion Treatment of retinal pigment epithelium detachment is difficult. Associating intravitreous injection of Ranibizumab, dynamic phototherapy, and sub‐conjunctival Triamcinolone provides good results. The sub‐cunjunctival administration allows to treat hypertonia.
Therapeutic effect of topical bevacizumab on corneal neovascularization following keratitis
Authors: DAMIJONAITYTE A , PAJAUJIS M , CIMBALAS A , BALTRUNIENE I , ASOKLIS R
Published: November 2010

Purpose To evaluate clinical results of the treatment with topically applied bevacizumab in patients with corneal neovascularization secondary to keratitis.

Methods A retrospective noncomparative case series report. 7 eyes of 7 patients with corneal neovascularization following ulcerative keratitis were treated with topical bevacizumab eye drops (5mg/ml) for 4 to 22 weeks. Underlying etiology of keratitis included 4 cases of herpetic infection, 2 cases of Pseudomonas aeruginosa infection and 1 case of keratitis e lagophthalmo. The follow‐up time was 4 to 25 weeks.

Results After the course of topical bevacizumab the decrease of corneal neovascularization was observed in all of the cases due to reduction of the diameter of the blood vessels and an involution of the small vessels’ network. At the baseline examination the mean extent of the neovascularized area of the cornea was 4.43 (SD 2.82, range 1‐9) clock hours in comparison with 2,57 (SD 2.15, range 1‐6) clock hours after the treatment, however, this difference was not statistically significant. The neovascularized area diminished in 5 eyes, the mean reduction being 1.86 (SD 1.57, range 1‐4) clock hours. In 2 eyes former epithelial defects of the cornea persisted without significant changes in the size or depth during the treatment. The rest of the eyes showed an epitheliazed, stable and noninflamed ocular surface. No local or systemic adverse effects of topical bevacizumab were noticed during the follow‐up time.

Conclusion Topical bevacizumab is an effective and well tolerated treatment for inhibiting corneal neovascularization secondary to keratitis of different etiologies.
New developments in dry eye treatment
Authors: BENITEZ‐DEL‐CASTILLO JM
Published: November 2010

Purpose This study summarizes the management and therapeutic options for treating dry eye disease. Goals of this review is to identify appropriate therapeutic methods for the management of dry eye disease and recommend a sequence or strategy for their application, based on evidence‐based review of the literature.

Methods To achieve this a comprehensive review of clinical textbooks and scientific literature was performed and the quality of published evidence graded according to an agreed standard, using objective criteria for clinical and basic research studies.

Results There have been tremendous advances in the treatment of dry eye and ocular surface disease in the last decades related to the increase in knowledge regarding the pathophysiology of dry eye. This has led to a paradigm shift in dry eye management from simply lubricating and hydrating the ocular surface with artiﬁcial tears to strategies that stimulate natural production of tear constituents, maintain ocular surface epithelial barrier function, and inhibit the inﬂammatory factors that adversely impact the ability of ocular surface and glandular epithelia to produce tears.

Conclusion The authors will present current and future treatment options for dry eye disease.
Dry eye syndrome and omega‐3 fatty acids
Authors: KAERCHER T
Published: November 2010

Purpose Dry eye disease is characterized by an inflammatory component of the ocular surface. Pathways to modulate inflammation include corticoids and cyclosporine. Omega‐3 fatty acids like eicosapentaenoic acid and docosahexaenoic acid represent an alternate pharmacologic way to influence the inflammatory cascade.

Methods Clinical studies.

Results An epidemiologic study in 32.470 healthy women showed that those with a higher intake of omega‐3 fatty acids had a 68% decreased prevalence of dry eye syndrome. Hyposecretory dry eye was tested after intake of omega‐3 fatty acids for 45 days. Symptoms, signs and inflammatory markers like HLA‐DR improved. Hyperevaporative dry eye improved after a long‐term supplementation with omega‐3 fatty acids with respect to symptoms, break‐up time and meibom score. Patients with refractive surgery (PRK) improved after omega‐3 fatty acids intake; this was derived from the OSDI‐score, Schirmer I test and tear clearance. In 102 contact‐lens wearers the symptoms and signs of dry eye improved after 12 weeks therapy with omega‐3 fatty acids.

Conclusion Nutricionals with omega‐3 fatty acids show evidence‐based effects on the inflammatory component of ocular surface disease and tear film disorder. Their beneficial effect was tested for hypovolemic and hyperevaporative dry eye. Patients after refractive surgery and contact lens wearers improved after supplementation, too. In contrast to the available anti‐inflammatory therapy the supplementation is apt for a long‐term application.
Chitosan in the treatment of dry eye
Authors: SCHMETTERER L , HÖLLER S , HORNOF M
Published: November 2010

Purpose To demonstrate the safety and efficacy of a new eye drop formulation containing a novel thiolated biopolymer, namely chitosan‐N‐acetylcysteine, in a number of pre‐clinical tests. It is postulated that interaction between thiol groups of the topically applied chitosan‐N‐acetylcysteine and cysteine‐rich mucin (MUC5AC) increases polymer residence time on the ocular surface and tear film stability.

Methods The efficacy of isotonic and buffered chitosan‐N‐acetylcysteine eye drops was evaluated in two different dry eye mouse models. The dosage dependent ocular residence time and biodistribution were investigated in a rabbit model using microPET technology. Long‐term irritation and delayed‐type hypersensitivity tests with chitosan‐N‐acteylcysteine eye drop formulation were conducted in rabbits.

Results In both dry eye studies mice treated with chitosan‐N‐acetylcysteine showed decreased expression of ocular surface mRNA of IL‐β, IL‐10, IL‐12α, and TNF, indicating that the formulation may have protective ocular surface properties. The residence time of chitosan‐N‐acetylcysteine eye drops on the ocular surface of rabbits was increased (detection up to 22h). Results of a long‐term ocular irritation study in rabbits demonstrate that the novel formulation is well tolerated and non‐irritant to the eye.

Conclusion Based on the promising pre‐clinical study results both in terms of efficacy and safety a clinical phase 1 trial is scheduled in the near future.

Commercial interest
The effect of riboflavin mediated corneal crosslinking on corneal hydration
Authors: KONTADAKIS G , GINIS HS , KARYOTAKIS N , PENNOS A , PENTARI IG , KYMIONIS G , PALLIKARIS IG
Published: November 2010

Purpose To evaluate the primary effect of corneal collagen crosslinking on corneal hydration.

Methods Twenty corneal buttons from freshly enucleated porcine eyes where immersed in riboflavin 0.1% in dextran 20% dilution for three hours in order for their hydration to reach an equilibrium. Corneal buttons where divided in two groups; the first group was stored in dark conditions while the other group was irradiated with UV radiation (390nm) for 30 minutes to stimulate collagen cross‐linking according to the clinically applied protocol. After irradiation all corneas were immersed in dextran 20% solution for 30 additional minutes and subsequently weighted. Finally all corneal buttons were dehydrated for 48 hours in a desiccating oven set at 62Co and weighted again to obtain their dry mass. Hydration (%) of each button was calculated. Results were analyzed with non parametric tests.

Results Irradiated group of corneas had statistically significant lower hydration than the non irradiated group. (p<0.05, Mann‐Whitney Test). Mean hydration in the irradiated group was 71% and in the non‐irradiated 75%.

Conclusion Collagen crosslinking causes corneal dehydration that can be detected immediately after the procedure. This phenomenon may contribute to increased mechanical stiffness of the cornea.
Safety and efficacy of femtosecond LASIK with reverse side cut
Authors: MENICACCI F , FRUSCHELLI M , MENICACCI C , MENICACCI FL , HADJISTILIANOU T
Published: November 2010

Purpose Laser in situ keratomileusis has several advantages over photorefractive keratectomy when performed properly in appropriate eyes. These include faster visual recovery, less discomfort after surgery, and milder and more predictable wound healing with less risk for haze. Lamellar corneal flap formation is the critical step in successful LASIK surgery. In our study we used femtosecond lasik with 90° hinge and 100 µm thickness flap wi

Methods We performed femtosecond lasik in 58 eyes of 30 patients (mean age 35 y.o.) with AMO's IntraLase™ FS and STAR S4 IR™ Excimer Laser System. Criteria for inclusion were spherical myopia of ‐2 to ‐8.00 D, hyperopia up to 5 D, astigmatism miopic/hyperopic up to 4.50 D; stable refraction for 2 years; a best‐spectacle corrected vision (BSCVA) of at least 20/25 in each eye. Corneal flap thickness was 100µm and hinge position was 90 degrees with reverse 120° side cut. The optical zone of the ablation was from 6.5 to 7 mm, transition zone from 8 to 9 mm.

Results Controls were made at 1day, 1 and 3 months. No flap decentration was observed in any case, we had one case of epithelial sloughing and one slightly irregular flap border. Spherical equivalent was within +/‐ 0.50 D and the cylinder was 0.50 D or less in all patients. Only 5% of patients showed marked discomfort and avversion to light for several days.

Conclusion Flap creation is probably the most important step during laser in situ keratomileusis (LASIK), and complications during it can affect the rest of the procedure and cause permanent visual loss. In our exeprience the use of 100µm thickness flap with oblique side cut demonstrated itself to be a safe procedure with a very low complications rate and good refractive results.
Corneal grafting assisted by wavelength‐optimised ultrashort pulser lasers
Authors: MARCIANO TAL , APTEL F , CHATEAU N , CROTTI C , DELOISON F , DRUON F , GEORGES P , HANNA M , LAMORY B , LEGEAIS JM , LEVECQ X , MORIN F , NUZZO V , PEYROT D , SAVOLDELLI M , PLAMANN K
Published: November 2010

Purpose We realized an innovative device for ocular surgery by ultrafast pulse laser optimised for corneal grafting.

Methods We constructed a demonstrator device that reproduces surgical conditions of corneal transplant. It is thus possible to realize with the help of an easy handling automatised interface all the kinds of already existing corneal transplants. Also, in order to maximize the spatial quality of the beam, a wavefront correction system using a deformable mirror module has been added. The Demonstrator contains an erbium fiber laser emitting at 1,6 microns. This laser delivers a beam of a few Joule with pulse duration of 700 femtoseconds and a repetition rate of 100‐200 KHz. It includes deformable mirrors permitting horizontal displacements and a wavefront sensor. It also contains the administration system of the laser beam.

Results The experiments carried out with a surgical tunable source confirmed the initial assumptions: the penetration depth is limited to wavelengths close to 1 microns. When increasing the wavelength, the drop of the scattering compensates the absorption and therefore the penetration depth is slowly varying when increasing the wavelength. The laser does not penetrate near the maximum of the water absorption band located at 1,45 microns. However, the use of a wavelength of 1,6 micros enables an important increasing of penetration depth (factor 3) while conserving the same energy of current technologies.

Conclusion The use of a laser source with a wavelength corresponding to the window of transparency of the cornea (1,65 microns) permits to increase both the penetration depth of an ultrafast laser source and the cut quality.
Tear film osmolarity after femtosecond laser‐assisted sub‐bowman keratomileusis. a pilot study
Authors: CANADAS SUAREZ P , GARCÍA‐GONZÁLEZ M , HERNÁNDEZ‐VERDEJO J , TEUS MA
Published: November 2010

Purpose To evaluate the tear osmolarity in patients that underwent Femtosecond laser‐assisted sub‐Bowman Keratomileusis (FSBK) three months before

Methods We performed a prospective observational study of consecutive eyes that had Femtosecond laser‐assisted Sub‐Bowman Keratomileusis. Three months post‐op, tear osmolarity was measured with the TearLab TM Osmolarity System. This measure was performed only in one eye per patient. A normality value of 308 ± 5 mOsm/L (provided by the manufacturer) was used to classify the tear osmolarity

Results 29 eyes of 29 patients were included in the study. Mean patient age was 43.5 ± 2.12 years (range, 25 to 64). Three months postop, mean osmolarity values were 304.5 ± 0.71 mOsm/L (range, 292 to 342). 17 eyes (60%) had a normal value of tear osmolarity (within ±2 standard deviation of the mean normal value), only 3 eyes (10%) had an hypo‐osmolar tear film and 9 eyes (30%) had an hyper‐osmolar tear film 3 months after FSBK

Conclusion Our results suggest that tear film osmolarity measured with the TearLabTM Osmolarity system tends to achieve normal values three months after Femtosecond laser‐assisted sub‐Bowman Keratomileusis, although one third of our patients still have a hyper‐osmolar tear film 3 months postop
From elementary concept in animal models to new frontiers in humans: neurovascular coupling in the ocular circulation
Authors: RIVA C
Published: November 2010

Purpose The retina and optic nerve, both optically accessible components of the central nervous system, are ideally suited for the investigation of the intrinsic physiological process by which blood ﬂow, metabolism and neural activity are tightly coupled (Roy and Sherrington. 1890).

Methods Using various techniques in the cat and human eye, the changes in blood flow in the retina and optic nerve in response to increased neural activity by flicker stimulation have been determined. The effect of varying the stimulus parameters, such as flicker modulation depth, frequency, luminance and red‐green color ratio, on the blood flow response was investigated. Putative mediators of the activity‐induced flow changes and the relationship between activity, blood flow and metabolic changes were assessed.

Results Visual stimulation with flicker increases rapidly and markedly both retinal and optic nerve blood ﬂows (functional hyperemia). Moreover, the data reveal unequivocally the presence, under specific conditions of flicker, of a neurovascular/neurometabolic coupling in these tissues, partly mediated by local potassium ions and nitric oxide production. Furthermore, the activity‐induced hyperemia is altered during a number of physiological and pharmacological interventions and in some pathologic conditions.

Conclusion Flicker stimulation of the retina offers a new and powerful means to modulate blood flow and investigate the neurovascular coupling in the neural eye tissues. Exploration of this activity‐induced hyperemia and the mechanism(s) underlying the neurovascular coupling will lead to an increased understanding of the pathophysiology of various ocular diseases.
Sex differences in uveal melanoma
Authors: DAMATO BE , COUPLAND SE
Published: November 2010

Purpose To determine sex differences in uveal melanomas involving choroid.

Methods Patients were included in this study if diagnosed clinically with uveal melanoma and treated after 1992 at the Liverpool Ocular Oncology Service. Survival studies were performed only with patients resident in mainland Britain, for whom accurate data from the NHS Cancer Registries were available. Statistical methods included the Chi‐square test for categorical variables, Mann‐Whitney for continuous variables and log‐rank for survival studies.

Results The 3870 patients comprised 1933 females and 1937 males. The mean age at treatment was 60.3 years with no significant difference (p = 0.78. The tumour was considered to arise in choroid in 91.3% of males and 86.0% of females (p<0.001).When only tumours involving choroid were assessed, males were less likely to have a melanoma with pre‐ora extension (p=.001); more likely to have tumour extension to within 2DD of disc or fovea (p = .001); greater basal diameter (p =.036), greater height (p = .003) and epithelioid cellularity (p =.018) but there was no difference in the prevalence of monosomy 3 (p =.574). Males were more likely to have primary enucleation (p = .015). Males showed greater metastatic mortality (p = .003); however, it is uncertain as to whether this difference was caused by bias relating to shorter life expectancy.

Conclusion Uveal melanomas tended to be more posterior in males, in whom choroidal melanomas tended to be larger with a higher prevalence of epithelioid cytomorphology. Males were more likely to undergo primary enucleation and showed higher metastatic mortality.
Serum proteomics in uveal melanoma
Authors: ANGI M , DAMATO BE , COUPLAND SE
Published: November 2010

Purpose Proteomics studies on uveal melanoma (UM) are limited and there is scope for further research that takes into account recent genetics insides.

Methods In this proposed study, serum samples from pat with UM will be collected before treatment and at various times afterwards and serum findings will be correlated with proteomics of the tumour itself. Patients will be included if they have UM involving choroid with full clinical and histological data and excluded if specimens do not meet required quality and quantity. It is envisaged that 30 patients from different centres will be recruited. Specimens will be processed using the MALDI‐TOF MS peptide profiling and 2D‐LC ItRAQ profiling approaches. Metastatic risk will be scored in a multivariate fashion.

Results Proteomics differences between primary tumour and serum will be evaluated in addition to statistical correlations with baseline data. The proteomic results of high risk and low risk patients (in respect to cytogenetics findings) will be compared.

Conclusion The findings of this study might identify markers predictive of metastatic disease and may complement existing serum studies.
The 7th edition of TNM predicts survival of patients with ciliochoroidal melanoma
Authors: KUJALA E , DAMATO BE , COUPLAND SE , DESJARDINS L , BECHRAKIS NE , GRANGE JD , HARBOUR W , KIVELÄ T
Published: November 2010

Purpose To document that staging ciliochoroidal melanoma by the Tumor, Node, Metastasis (TNM 7th edition) system is reproducible between centres.

Methods Data of 8252 patients (Berlin 689, Helsinki 270, Liverpool 3305, Lyon 473, Paris 3515) regarding tumour thickness, largest basal diameter, ciliary body and extrascleral extension were staged centre by centre. Stage‐specific survival was compared between centres using Kaplan‐Meier analysis and log rank test.

Results Of these tumours, 21% (13‐25%) classified to stage I, 31% (28‐34%) to stage IIA , 23% (19‐32%) to stage IIB, 17% (16‐19%) to stage IIIA, 7% (5‐11%) to stage IIIB and 1% (0‐4%) to stage IIIC, respectively. The survival of patients treated in the five European ocular oncology centers differed significantly overall, probably because of differences in case mix and follow‐up. The survival did not differ significantly between centers in stage groups other than IA (P<0.014 and compared to P<0.013 in stage IIA, P<0.001 in IIB, P<0.001 in IIIA; P<0.001 in IIIB and P<0.003 in IIIC). The corresponding 5‐year survival rates for stages I, IIA‐B and IIIA‐C were 96% (87‐99% in 4 different centers), 89% (74‐93%), 82% (73‐85%), 67% (60‐81%), 46% (33‐61%) and 26% (12‐31%) by 5 years; and 88% (74‐89%), 80% (68‐82%), 68% (60‐65%), 45% (37‐53%), 28% (17‐33%) and 10% (7‐12%) by 10 years, respectively. In the fifth centre, the 5‐ and 10‐year survival rates were 82% and 74% even for Stage IIIB.

Conclusion The first evidence‐based TNM classification of malignant ciliochoroidal melanoma equally predicts survival of patients in four of five different European ocular oncology centers regardless of their different case mix and preferred follow‐up and treatment practices.
Time course of diagnosis and treatment of uveal melanomas in a intraocular tumors unit
Authors: VICENTE TIERNO N , SAORNIL MA , GARCIA‐ALVAREZ C , ALMARAZ A , GIRALDO A , LOPEZ‐LARA F , DE FRUTOS J
Published: November 2010

Purpose To analyze the time course of diagnosis and treatment of uveal melanomas in an ocular referral unit in a period of 20 years.

Methods Prospectively collected data on consecutive patients diagnosed of uveal melanoma, from 1990 to 2010, were analyzed. Epidemiologic and general data, clinical and tumor characteristics at the time of diagnosis (visual acuity, activity signs, size and location) and treatment were collected in a Microsoft access database. Three periods were established: 1990‐2000, 2000‐2005 and 2005‐2010, in order to compare tumor characteristics and treatment. Statistical analysis was performed by Pearson’s Chi‐square test to compare differences.

Results From a total of 378 patients 85 were diagnosed in the first period, 146 in the second, and 146 in the third one. Melanoma was diagnosed in a routine examination in 121 patients and in 248 cases due to the presence of symptoms, with a similar distribution in the three periods, p=0.206. Visual acuity (VA) showed a tendency to decrease along time, VA<=0.1 represented 25.9% of all the cases, being the first period 18.4% and 31% in the third one (p=.009). Tumor size and macular involvement tend to decrease, p<0.05. Activity signs showed no differences along time. The number of patients treated with brachytherapy has increased with 25.9% before 2000, up to 42.1% after 2006 (p=.001), showing a decrease in enucleation from 38.8% to 24.4% (p=.002)

Conclusion The diagnosis of uveal melanoma is showing smaller tumors but with worse visual acuity it can not be explained by changes in size, macular involvement or activity signs. The increased conservative treatments are allowing to preserve eye and visual function.
Clear temporal corneal incision versus superior in cataract surgery: comparison corneal sensitive of nerve fibers
Authors: PESCE G , MACINAGROSSA G , MINERVA G , CANTATORE A , MONTRONE L , DE BELLIS A , DI GESU I , MONTRONE F , RICCHETTI R
Published: November 2010

Purpose Purpose of this study was to observe the differences of corneal sensitive innervation with temporal or superior incision in cataract surgery. Most of the sensory nerve fibers are distributed in the cornea in the nasal and temporal regions; this one is the most frequent point of access for phacoemulsification cataract.

Methods were observed 30 patients operated on for bilateral cataracts, aged between 50 and 75 years, both male and female.All patients had no other eye disease, had undergone previous surgery or presented with diabetes or hypertension.The operation was cataract phacoemulsification with implantation of intraocular lens.All patients were performed by an evaluation of the cornea with “ ConfoScan 3 Nidek” to analyze the innervation before and after surgery for cataract in different locations.

Results Results we have at the moment tell us that the superior incision is less harmful for corneal sensitive nerve fibers. This result involves that patients have less ocular discomfort and pain in successive months.

Conclusion This kind of surgery would be ideal to avoid a long and painful course to the patients, although this surgery approach is more difficult.
Spectroscopic features in relation to corneal hydration during excimer laser ablation
Authors: GINIS HS , MAKRIDAKI M , ANGLOS D , PALLIKARIS IG
Published: November 2010

Purpose To record the spectrum emitted during excimer laser‐cornea interaction at fluences intensities resulting to ablation and investigate the relation between its spectroscopic features and corneal hydration.

Methods Porcine corneas from eyes obtained from a local abattoir were used for the experiments. The corneal samples were de‐epithelialized and the stroma was irradiated with an ArF excimer laser (TuiLaser Braggstar 200, ArF ; λ=193 nm) The energy fluenc used varied between 180 to 250 mJ/cm2. Emission spectra for 6 hydration levels ranging from 78 to 92% were recorded.

Results The spectra recorded real‐time during the laser‐tissue interaction imply the existence of plasma and molecular fluorescence while the atomic lines of Na and Ca were detected. Differences in the shape of the recorded spectra were observed for corneas at different hydration levels. It is hypothesized that this is due to the stronger molecular fluorescence emitted when over hydrated corneas are irradiated. Molecular fluorescence detected from over hydrated corneas was matched to the fluorescence spectra of tyrosin and tryptophane, 2 amino acids found in low concentration in collagen.

Conclusion Differences in the intensity of molecular fluorescence were detected in the plume emitted when irradiating corneas at different hydration levels. This finding may find an application in the real‐time estimation of corneal hydration during refractive surgery
3D reconstruction of endothelial surface of organ‐cultured corneas to improve their quality control
Authors: THURET G , FERNANDES M , GAVET Y , PINOLI JC , PISELLI S , ACQUART S , GAIN P
Published: November 2010

Purpose Corneal endothelium of organ cultured cornea forms a 3D surface because of corneal curvature and of the Descemetic folds (of hundreds of μm depth) that appear during storage. Eye bank technicians have therefore a risk of endothelial cell density (ECD) overestimation when counting on an image projection. Our aim is to develop a 3D reconstruction from a Z stack of images in order to take account of the local slope and increase ECD reliability

Methods Z stacks of 35 images were acquired with a motorized light microscope (BX41, Olympus) through a x10 objective. After routine eye bank preparation with saline, EC appeared with a clear cytoplasm and dark borders but could locally show a contrast reversal. In each section, the best‐focused pixels were determined using focus measurement algorithms. Depth map and texture image were then separately generated and the 3D reconstruction was obtained by projecting the texture image onto the depth map. A new algorithm, based on projections onto eigenbases, was developed and compared to 5 existing algorithms. Comparison was done using 1/ simulated images with additive noises to assess the reliability and noise robustness 2/ true endothelial image

Results The new algorithm exhibited a more robust behaviour in presence of noise than the other algorithms. 3D endothelial reconstructions were also visually better, especially in case of local contrast reversal

Conclusion Using a technology easily transposable into an eye bank, a reliable 3D reconstruction is possible from routine images that are often of average quality with poor contrast and high background noise. Our next step is to integrate the local slope information to correct local ECD
Evaluation of unpreserved dexamethasone phosphate 0.1% versus placebo in patients with severe keratoconjunctivitis sicca (KCS) due to Sjögren's syndrome (SS)
Authors: MANSOUR K , ZAAL MJ
Published: November 2010

Purpose KCS in SS is often associated with chronic inflammation. Moreover epithelial damage induces a release of local prostaglandins. Corticosteroids are potent inhibitors of many inflammatory pathways.

Methods 21 patients were included in a double masked, intra‐individual comparison versus placebo, in patients with bilateral severe KCS due to SS. One drop of dexamethasone 0.1% was instilled in one eye tid during the first week of the study, bid during the following 2 weeks and qd during the last 2 weeks. One drop of placebo was instilled in the contra‐lateral eye with the same schedule. Patients attended 3 visits: D0, D7 and D35. A phone call was made on D70 to collect AEs and assess ocular discomfort. Symptomatology within the last 48h was evaluated on a VAS. Ocular symptoms and signs and safety were recorded at each visit.

Results Both treatments resulted in a decrease of the patient’s ocular discomfort. At Day 35, a significant difference was found between the two treatments for the patient’s feeling of ocular discomfort, with better values under dexamethasone (p=0.007). No significant difference between treatments was observed on signs. But, the difference in Lissamine green total score between the 2 treatments almost reached statistical significance in favour of dexamethasone on D7 (p=0.056) and conjunctival hyperaemia improved faster with dexamethasone, as soon as D7. Investigators seemed to be more satisfied by the dexamethasone treatment both on Day 7 and Day 35. No statistically significant difference in overall tolerance assessments was observed between the two treatment groups.

Conclusion Unpreserved dexamethasone 0.1% eye drops improve symptoms and signs due to KCS in SS.
Ulrastructural features of keratoconus cornea of 16 year old Saudi male and female patients
Authors: AKHTAR S , ABDELRAHMAN K , ALMUBRAD TM
Published: November 2010

Purpose Prevalence of keratoconus in Saudi Arabia is very high. In the present study we investigated ultrastructural alteration in keratoconus cornea of 16 year old male and female patients.

Methods The sixteen year old male and female Saudi patients underwent lamellae keratoplasty. The keratoconus corneas of the patients were fixed in 2.5% glutaraldehyde containing cuprolinic blue in sodium acetate buffer and processed for electron microscopy.

Results In both patients similar structural changes were observed. Epithelium was normal but hemidesmosomes degenerated in numerous places. Basement membrane was thin followed by degenerate Bowman’s layer (BW). Near the scar region, BW layer was replaced by fibrous pannus. Stromal lamellae undulated in most parts of the stroma. The lamellae in the anterior stroma were very steep and invaginating into the BW, pushing basal epithelial cells. There were microfilaments present within lamellae. Large amounts of large PGs were arranged around collagen fibrils of variable diameters. Degenerate keratocytes were embedded in between lamellae and contained PGs. In the middle stroma, parallel running lamellae were very thin. In the scar region, in the anterior stroma collagen fibrils were oriented (running) in random directions instead of running parallel.

Conclusion Typical severe keratoconus changes were observed in our patients at a young age, which usually occurs in elderly keratoconus patients. These stromal changes could be due to a disorder in the synthesis of PGs which influence the organisation of collagen fibrils that results in weakening of lateral lamellar cohesion as has been reported previously.
Risk of endophthalmitis in minimally invasive surgery
Authors: TAN HS
Published: November 2010

Abstract not provided
Patterns of chromatic sensitivity loss in AMD and DB
Authors: O'NEILL‐BIBA M , SIVAPRASAD S , RODRIGUEZ M , WOLF JE , BARBUR JL
Published: November 2010

Purpose Age‐Related Macular Degeneration (AMD) and Diabetic Retinopathy are leading causes of blindness in developed countries in the aged and working population, respectively. Both diseases lead to slow changes in retinal cell structure and corresponding functional loss. The aim of this study was to detect and quantify the degree of acquired loss for both disease types through the use of sensitive visual assessment of chromatic sensitivity (CS). The patterns of loss in the two groups were compared and correlated with clinical indices of disease severity.

Methods Subjects with various levels of retinopathy and maculopathy were recruited for the study. Red‐Green (RG) and Yellow‐Blue (YB) CS was measured in both disease groups and in age‐matched controls using the Colour Assessment and Diagnosis Test (CAD). Similar data measured in 330 normal trichromats provided the statistical limits for RG and YB CS.

Results All AMD subjects exhibited YB CS loss in the initial stages of the disease. Unequal RG and YB losses were reported in advanced AMD, with YB being the most affected. Diabetic subjects (DB) on the other hand, showed almost equal RG and YB CS losses (r=0.98), irrespective of the type of diabetes or presence of retinopathy. The extent of CS loss as assessed with the CAD test, correlated well with disease severity in AMD subjects and with HbA1c levels in DB subjects.

Conclusion Two distinct patterns of CS loss emerged from this study: AMD revealed predominantly tritan‐like losses while DB showed almost equal RG and YB CS loss, irrespective of disease severity. Results suggest that accurate assessment of chromatic discrimination provides a sensitive measure of retinal function and can be used to monitor disease progression or the effectiveness of treatment.