A Real-World, Multicenter, 6-Month Prospective Study in Greece of the Effectiveness and Safety of Ranibizumab in Patients with Age-Related Macular Degeneration Who Have Inadequately Responded to Aflibercept: The "ELEVATE" Study.

Purpose: Real-world evidence on short-term outcomes of ranibizumab in wet age-related macular degeneration (wAMD) following inadequate response to aflibercept is scarce. This study aimed to evaluate the functional and anatomic effects of switching to ranibizumab in cases of wAMD previously treated with aflibercept with inadequate response. Patients and Methods: Prospective, observational study performed in eight ophthalmology hospital/private clinics in Greece, enrolling consented patients with active wAMD, ≥50 years-old, who had initiated ranibizumab ≥28 days and <2 months after their last aflibercept injection. Data were collected at enrollment, and at 1, 3 and 6 months post-treatment onset (post-baseline). Results: Between September-2015 and November-2017, 103 eligible patients (56.3% females; mean age: 74.8±8.6 years) were consecutively enrolled. The age at AMD diagnosis in the study eye was 71.3±8.8 years. Aflibercept (median of 5 injections received over 11.3 months) had been discontinued for anatomical (in 69.9%) and/or functional (38.8%) reasons. At baseline (median: 24.3 months after wAMD diagnosis), choroidal neovascularization was occult in 69.1% of evaluable study eyes; 60.2% of the study eyes had pigment epithelial detachment (PED); 42.7% cysts; 21.4% fibrosis; 66.0% subretinal, and 59.2% intraretinal fluid. At 6 months post-baseline: a median of 3 ranibizumab injections (range: 1-6) had been received; the best-corrected visual acuity (BCVA)≥0 letter gain rate was 81.8%; the BCVA ≥15 letter gain rate was 17.0%; BCVA gain was 3.2 letters [mean increase: 3.2±10.0 letters; median: 0.0; p = 0.002]; PED greatest basal diameter (GBD; median: 1470.5 µm) also decreased (median decrease: 114.0 µm; p = 0.019). Baseline central retinal thickness (CRT; median: 312.0 µm) remained unchanged. One patient permanently discontinued ranibizumab due to adverse event occurrence, assessed as not causally related to ranibizumab. There were no ranibizumab-related adverse reactions. Conclusion: Six-month treatment with ranibizumab in aflibercept inadequate responders led to visual acuity and PED GBD improvements, with no statistically significant CRT change.

Protective antioxidant effects of saffron extract on retinas of streptozotocin-induced diabetic rats.

Objective: Oxidative stress plays an important role in the pathogenesis of diabetic retinopathy. The aim of the present study was to investigate the effect of Crocus sativus L. styles (saffron) extract on oxidative stress indices of retina in streptozotocin (STZ)-induced diabetic rats. Methods: Adult male Wistar rats (n=20) were randomized into the following 4 groups (n=6-7/ group): Control group (C): normal, Control + Saffron group (CS): non-diabetic rats treated with 60 mg/ kg of saffron extract, Diabetic group (D) and Diabetic + Saffron group (DS): diabetic rats treated with 60 mg/ kg saffron extract. We determined the activity of superoxide dismutase (SOD), glutathione peroxidase (GPx) and catalase (CAT) as markers of antioxidant response, as well as malondialdehyde (MDA) as a marker of lipid peroxidation. Results: Induction of diabetes caused a significant decline in the activities of CAT (76.43%), SOD (53.43%) and GPx (77.58%). MDA levels were significantly lower in the DS group (0.878 ± 0.375 nmol MDA/ mg protein) as compared to D group (1.950 ± 0.299 nmol MDA/ mg protein, p<0.01) and in the CS group (0.503 ± 0.221) in comparison to C group (1.699 ± 0.454, p<0.01). Moreover, SOD and GPx activities were significantly higher (more than 1.5 and 3.5-fold respectively) after treatment with saffron (p<0.01). Regarding the retinas of non-diabetic animals, the administration of the extract caused an > 1.8-fold increase in the activity of CAT (p<0.05) and a 3-fold decrease in MDA levels (p<0.01). Conclusions: This study showed that saffron extract has a protective antioxidant action in retinas of diabetic rats. Abbreviations: C = Control group, CS = non-diabetic rats diabetic rats treated with 60 mg/ kg saffron extract, D = diabetic group, DS = diabetic rats treated with 60 mg/ kg saffron extract, SOD = superoxide dismutase, GPx = glutathione peroxidase, CAT = catalase, MDA = malondialdehyde, DM = diabetes mellitus, DR = diabetic retinopathy, ROS = reactive oxygen species, STZ = streptozotocin, GSH = reduced glutathione.

UVB-mediated down-regulation of proteasome in cultured human primary pterygium fibroblasts.

BACKGROUND: Pterygium is a condition characterized by epithelial overgrowth of the cornea, inflammatory cell infiltration and an abnormal extracellular matrix accumulation. Chronic UV exposure is considered as a pathogenic factor of this disease. Proteasome is an intracellular multi-subunit protease complex that degrades intracellular proteins. Among proteasome subunits the ß5 (PSMB5), bearing chymotrypsin-like activity. It is considered as the main proteasome subunit and its expression is mediated by Nrf2-ARE pathway in many cell types. This study investigates the expression of PSMB5 in pterygium and the effect of UVB irradiation on its expression and activity in pterygium fibroblasts. METHODS: Normal conjunctival and pterygium specimens were obtained from the bulbar conjunctiva of patients undergoing cataract surgery and from patients with pterygium undergoing surgical removal of primary tissue, respectively. Fibroblasts were isolated upon treatment of specimens with clostridium collagenase. The expression of PSMB5 and Nrf2 in tissues and cells was ascertained by RT-PCR analysis and western blotting. Cell survival was measured by the MTT method and the proteasome chymotrypsin-like activity was determined by fluorometry. RESULTS: RT-PCR analysis showed that the expression of PSMB5 was significantly lower in pterygium than in normal conjunctiva. The expression of PSMB5 was mediated by the Nrf2/ARE pathway as indicated by using the Nrf2 activator Oltipraz. The expression of PSMB5 and Nrf2 by pterygium fibroblasts was suppressed in a dose dependent manner following UVB radiation of 0-50 mJ/cm2 doses. The expression of PSMB5, but not of Nrf2, remained at almost the control levels, when UVB exposure was performed after pre-incubation of cells with the src kinases inhibitor PP2. UVB irradiation had very low deleterious effect on fibroblasts survival, while it did not affect the proteasome chymotrypsin-like activity. CONCLUSION: In pterygium fibroblasts, UVB exposure leads to down-regulation of Nrf2/ARE-mediated PSMB5 gene expression, in which src kinases may be implicated. This effect may be partially responsible for the lower expression of PSMB5 detected in pterygium as compared to normal conjunctiva.

Immunolocalization of cannabinoid receptor type 1 and CB2 cannabinoid receptors, and transient receptor potential vanilloid channels in pterygium.

Cannabinoids, as multi­target mediators, activate cannabinoid receptors and transient receptor potential vanilloid (TRPV) channels. There is evidence to support a functional interaction of cannabinoid receptors and TRPV channels when they are coexpressed. Human conjunctiva demonstrates widespread cannabinoid receptor type 1 (CB1), CB2 and TRPV channel localization. The aim of the present study was to investigate the expression profile for cannabinoid receptors (CB1 and CB2) and TRPV channels in pterygium, an ocular surface lesion originating from the conjunctiva. Semi­serial paraffin­embedded sections from primary and recurrent pterygium samples were immunohistochemically examined with the use of specific antibodies. All of the epithelial layers in 94, 78, 96, 73 and 80% of pterygia cases, exhibited CB1, CB2, TRPV1, TRPV2 and TRPV3 cytoplasmic immunoreactivity, respectively. The epithelium of all pterygia cases (100%) showed strong, mainly nuclear, TRPV4 immunolocalization. In the pterygium stroma, scattered cells demonstrated intense CB2 immunoreactivity, whereas vascular endothelial cells were immunopositive for the cannabinoid receptors and all TRPV channels. Quantitative analyses of the immunohistochemical findings in epithelial cells demonstrated a significantly higher expression level in conjunctiva compared with primary pterygia (P=0.04) for CB1, but not for CB2 (P>0.05). Additionally, CB1 and CB2 were significantly highly expressed in primary pterygia (P=0.01), compared with recurrent pterygia. Furthermore, CB1 expression levels were significantly correlated with CB2 expression levels in primary pterygia (P=0.005), but not in recurrent pterygia (P>0.05). No significant difference was detected for all TRPV channel expression levels between pterygium (primary or recurrent) and conjunctival tissues (P>0.05). A significant correlation between the TRPV1 and TRPV3 expression levels (P<0.001) was detected independently of pterygium recurrence. Finally, TRPV channel expression was identified to be significantly higher than the expression level of cannabinoid receptors in the pterygium samples (P<0.001). The differentiated expression of cannabinoid receptors in combination with the presence of TRPV channels, in primary and recurrent pterygia, imply a potential role of these cannabinoid targets in the underlying mechanisms of pterygium.

Diclofenac for pain associated with intravitreal injections: a prospective, randomized, placebo-controlled study.

IMPORTANCE: Intravitreal injections (IVI) are often painful. BACKGROUND: To evaluate the analgesic effect of diclofenac in patients undergoing IVI. DESIGN: Single-centre, prospective, randomized, triple-arm, placebo-controlled, interventional study in the University Hospital of Patras. PARTICIPANTS: Seventy-four patients. METHODS: Group 1 (n = 25) received topical diclofenac 45 min before IVI, Group 2 (n = 25) received oral diclofenac 4 h before IVI and topical diclofenac while Group 3 (n = 24) received placebo before IVI. Using the short form of the McGill Pain Questionnaire (SF-MPQ), pain intensity was assessed with the visual analogue scale (VAS), the main component of the SF-MPQ and the Present Pain Intensity (PPI) scores immediately and 6 h post-IVI. MAIN OUTCOME MEASURES: The VAS pain score immediately post-IVI. RESULTS: Immediately post-IVI, patients in Group 2 reported significantly lower VAS pain scores compared to placebo while no statistically significant difference was found between patients that received topical diclofenac and placebo. Six hours post-IVI, patients in both treatment groups reported significant lower VAS pain scores compared to placebo. The scores of the main component of the SF-MPQ were significantly lower in patients of treatment groups compared to placebo at both time-points. Finally, while no statistically significant difference was found between the 3 Groups in PPI scores immediately post-IVI, 6 h later, patients of both treatment groups reported significantly lower PPI scores compared to placebo. CONCLUSIONS AND RELEVANCE: The combination of topical and oral diclofenac demonstrated better analgesic effect than topical diclofenac administration in patients undergoing IVI immediately and up to 6 h post-IVI.

Efficacy of Topical Ofloxacin 0.3 % Administration on Conjunctival Bacterial Flora in Diabetic Patients Undergoing Intravitreal Injections.

PURPOSE: This prospective, randomized case series study aims to evaluate the efficacy of ofloxacin 0.3% eye drops in eradication of conjunctival bacterial flora in diabetic patients undergoing intravitreal injections (IVI). METHODS: Ninety-two diabetic patients (92 eyes) scheduled to undergo intravitreal injection of ranibizumab due to diabetic macular edema were enrolled in the study. Patients were randomly assigned to three different groups. Group 1 (n=32) received ofloxacin eye drops the day before before IVI (four times); patients in Group 2 (n=29) were administered ofloxacin one hour before IVI (every 15 minutes), while Group 3 (n=31) comprised patients that received combined administration of ofloxacin both one day and one hour before IVI (eight doses). Samples were collected from the injection site before and after antibiotic administration. Culture results from BACTEC broth and positive cultures in blood agar and Sabouraud's dextrose agar plates were measured. RESULTS: In Group 1, BACTEC broth positive cultures decreased from 84.4% at baseline to 50% after ofloxacin administration (p=0.007), and blood agar positive cultures reduced from 65.63% to 34.38% (p=0.02). In Group 2, positive cultures significantly decreased in BACTEC broth (from 79.3% at baseline to 48.28%; p=0.027) and in blood agar (from 68.97% to 37.13%; p=0.034). In Group 3, positive cultures decreased from 77.42% at baseline to 32.26% (p=0.0008) and from 58.06% at baseline to 22.58% (p=0.009) in BACTEC broth and blood agar, respectively. No microorganisms were isolated from Sabouraud's dextrose agar plates. CONCLUSIONS: The combined one day/one hour (eight doses) ofloxacin administration in diabetic patients is extremely effective in reducing conjunctival bacterial flora. The application of topical ofloxacin for one day or one hour before IVI is also significantly effective.

Guidelines for the Management of Wet Age-Related Macular Degeneration: Recommendations from a Panel of Greek Experts.

PURPOSE: To propose guidelines for the management of patients with wet age-related macular degeneration (wAMD), taking into account the results of large multicenter studies and clinical experience of retina experts. METHOD: A team of retina experts developed a consensus paper after three consecutive meetings. The group was focused on guidelines to help clinical decision-making around the definition of successful treatment and the definition of non-response to therapy. RESULTS: Parameters suggestive of a successful response to treatments included: any gain in best corrected visual acuity (BCVA) or vision loss that is less than 5-10 Early Treatment Diabetic Retinopathy Study (ETDRS) letters, reduction of central retinal thickness, partial or complete absorption of subretinal fluid (SRF), reduction of intraretinal fluid, reduction of pigment epithelial detachment or restoration of the anatomy of outer retinal layers. Non-response to current treatment was considered in the case of loss of BCVA greater than 10 ETDRS letters, increased retinal edema or increase of SRF as evidenced by optical coherence tomography or new bleeding in biomicroscopy. CONCLUSION: The introduction of anti-VEGF agents revolutionized the treatment of wAMD. Given the complexity of the disease, the emerging new agents and the difference of cases recruited in clinical trials compared to those appearing in every-day practice, it is essential to individualize treatment options taking into account the results of clinical trials.

Ηypoxia-inducible factor-1α, von Hippel-Lindau protein, and heat shock protein expression in ophthalmic pterygium and normal conjunctiva.

PURPOSE: Εnhanced expression of transcription factor hypoxia inducible factor HIF-1α is known to play a critical role in the modulation of cell metabolism and survival pathways as well as having stem-cell-like properties. Furthermore, accumulated data reveal the existence of cross-regulation between the oxygen-sensing and heat shock pathways contributing to the adaptation of cells under stressful conditions. Pterygium, a stem cell disorder with premalignant features, has been reported to demonstrate hypoxia. The purpose of this study was to investigate the co-expression patterns of transcription factor HIF-1α and von Hippel Lindau protein (pVHL)--which normally acts to keep levels of HIF-1α activity low under normoxic conditions--in pterygium and normal conjunctival human samples. Additionally, expression of HIF-1α compared to the activation of heat shock proteins (Hsp90, Hsp70, and Hsp27) was studied. Emphasis was placed on the detection of HIF-1α and Hsp90, which associates with and stabilizes HIF-1α to promote its transcriptional activity. METHODS: Semi-serial paraffin-embedded sections and tissue extracts from pterygium and normal conjunctival samples were studied by immunohistochemistry and western blot analysis, respectively, with the use of specific antibodies. Double labeling immunofluorescence studies on cryostat sections were also included. RESULTS: Statistically significant increased expression of HIF-1α and Hsps (Hsp90, Hsp70, and Hsp27) in pterygia compared to normal conjunctiva was demonstrated (p<0.05). In contrast, no significant difference was detected for pVHL expression (p>0.05). Immunohistochemical findings revealed nuclear HIF-1α immunoreactivity in all the epithelial layers of 23/32 (71.8%) pterygium tissues. Furthermore, all epithelial layers of the majority (75%) of pterygium samples showed strong cytoplasmic immunoreactivity for Hsp27 while Hsp27 expression was detected in all pterygia (100%) examined. Hsp27 expression was not observed in the superficial layer of goblet cells. In some samples, focal basal epithelial cells exhibited weak Hsp27 expression or were Hsp27 immunonegative. Ιmmunoreactivity of phopsho-Hsp27 showed the same distribution pattern as Hsp27 did. Epithelium of all pterygia (100%) displayed moderate to strong Hsp90 cytoplasmic immunoreactivity. Furthermore, the majority of pterygia, specifically, 30/32 (93.7%) and 27/32 (84.3%) demonstrated, respectively, Hsp70 and pVHL cytoplasmic immunoreactivity. Hsp90, Hsp70, and pVHL immunoreactivity was mainly detected in basal and suprabasal epithelial layers even though strong immunoreactivity in all epithelial layers was also observed in some pterygia. Stroma vessels were immunopositive for Hsps (Hsp90, Hsp70, and Hsp27) and pVHL. A statistically significant correlation between the expression of HIF-1α and the activation status of Hsps (Hsp90, Hsp70, and Hsp27; p<0.05) was observed whereas HIF-1α expression did not correlate with pVHL expression (p>0.05). Double labeling immunofluorescence studies showed nuclear HIF-1α co-localization with cytoplasmic Hsp90 expression in cells distributed in the entire epithelium of pterygia, in contrast to, normal conjunctiva, which exhibited only a few scattered epithelial cells with cytoplasmic HIF-1α expression and basal epithelial cells with Hsp90 expression. CONCLUSIONS: The upregulation of coordinated activation of HIF-1α and Hsps in pterygium may represent an adaptive process for the survival of cells under stressful conditions. The significance of the association of HIF-1α with Hsp90 with respect to the therapeutic approach of pterygium requires further evaluation.

Complement C3, C2, and factor B gene polymorphisms and age-related macular degeneration in a Greek cohort study.

PURPOSE: To elucidate whether polymorphisms of C2, C3, and CFB genes are major genetic determinants of age-related macular degeneration (AMD) in a Greek population. METHODS: This was a case-control association study comprising 120 Greek patients with early and late-stage AMD and 140 independent controls of Caucasian origin. All participants were genotyped for rs547154, rs2230199, rs641153, and rs12614 polymorphisms by a combination of PCR and direct DNA sequencing assays. RESULTS: The frequency of the rs2230199 G allele (minor allele) was significantly higher in patients with AMD in comparison with controls (0.34 vs 0.22, p = 0.0031) and similar to the frequency of other reported populations. There was a significant difference in the frequencies of the rs2230199 genotypes among cases and controls (p = 0.0055). rs2230199 was found to be a significant predictor of advanced AMD status (odds ratio 6.41, confidence interval [CI] 2.72-15.09, p<0.0001; area under the curve 0.706, CI 0.61-0.78, p<0.0001]). For the other single nucleotide polymorphism (SNP) loci, the allele and genotype frequencies did not reach statistical significance. The minor allele frequencies in controls and cases were similar and still much lower than the frequencies reported in other populations. CONCLUSIONS: The rs547154, rs641153, and rs12614 SNPs were not associated with AMD development in Greek patients. However, this finding should be viewed with caution as the particular polymorphisms presented with very low frequencies in the Greek population. Finally, the replication of the reported associations of C3 with AMD suggests that the presence of the C3 G allele could serve as a high-risk genetic marker for the development of AMD and the progression of the disease to the advanced clinical stage.

Atypical Cogan's syndrome presenting as bilateral endogenous endophthalmitis.

We report a case of atypical Cogan's syndrome presenting as bilateral endogenous endophthalmitis in a woman with ovarian cancer. A 62-year-old woman with ovarian cancer developed bilateral interstitial keratitis and panuveitis accompanied by bilateral sensorineural hearing loss and chondritis. Auricular cartilage biopsy ruled out relapsing polychondritis and the diagnosis of atypical Cogan's syndrome was set clinically.

Idiopathic retinal vasculitis, arteriolar macroaneurysms and neuroretinitis: clinical course and treatment.

BACKGROUND: The purpose of the study is to describe the clinical course and treatment of idiopathic retinitis, vasculitis, aneurysms and neuroretinitis. The study utilized non-randomized, retrospective and interventional case series. The eight eyes of six patients were analysed. Testing included wide fluorescein angiography, indocyanine green angiography and systemic evaluation. Treatment involved observation, panretinal laser photocoagulation (PRP) for peripheral retinal ischemia, grid laser for macular oedema and focal laser on the macroaneurysms. The main outcome measures were initial visual acuity (VA), initial stage at diagnosis, clinical course, surgical intervention, final VA, final stage and complications of disease. RESULTS: Five out of eight eyes with retinal ischemia in more than two quadrants that were treated with PRP and grid laser for macular oedema maintained excellent VA and demonstrated no progression of retinal ischemia during follow-up. The two eyes which exhibited retinal ischemia in less than two quadrants and macular oedema were treated with grid laser and focal laser on the macroaneurysms, but did not undergo PRP. VA improved by two lines of the Snellen chart, and there was no progression of retinal ischemia during the 3 and 4 years of follow-up. One eye with neither retinal ischemia nor macular oedema was not treated, and the clinical picture remained stable during the follow-up. CONCLUSION: Early PRP may be considered in the presence of angiographic evidence of peripheral retinal non-perfusion. However, treatment could be withheld until the patient develops retinal ischemia in more than two quadrants.

Brinzolamide-timolol fixed combination for the prevention of intraocular pressure elevation after phacoemulsification.

BACKGROUND: To evaluate the efficacy of brinzolamide-timolol fixed combination in intraocular pressure during the first 24 h after uneventful phacoemulsification cataract surgery using Viscoat and Provisc. DESIGN: Prospective randomized comparative case series. PARTICIPANTS: Ninety-two eyes of equal patients scheduled for phacoemulsification cataract surgery. METHODS: Treatment group (52 eyes) received a drop of brinzolamide-timolol fixed combination immediately after surgery. Control group (40 eyes) received no treatment. MAIN OUTCOME MEASURES: Intraocular pressure preoperatively and at 6, 12 and 24 h postoperatively. RESULTS: Six hours after surgery the mean intraocular pressure decreased by 0.3 ± 2.95 mmHg (P > 0.05) in the treatment group and increased by 6.8 ± 2.78 mmHg (P < 0.001) in the control group. Twelve hours postoperatively, the mean intraocular pressure increased by 0.23 ± 3.49 mmHg (P > 0.05) in the treatment group and by 5.3 ± 3.26 mmHg (P < 0.001) in the control group. Twenty-four hours after surgery, the mean intraocular pressure decreased by 1.76 ± 2.83 mmHg (P < 0.01) in the treatment group and in the control group increased by 1.4 ± 2.46 mmHg (P > 0.05). The intraocular pressure in the treatment group was statistically significantly lower compared with the control group at 6, 12 and 24 h postoperatively. None of the eyes in the treatment group had postoperative intraocular pressure elevation ≥10 mmHg; such an increase was recorded in 20% and 10% of control eyes at 6 and 12 h after surgery, respectively. CONCLUSION: A single dose of brinzolamide-timolol fixed combination after phacoemulsification cataract surgery prevented a significant intraocular pressure increase during the first 24 h postoperatively.

Effect of ketorolac 0.5% drops on patients' pain perception during intravitreal injection procedure.

PURPOSE: To evaluate the analgesic effect of ketorolac 0.5% drops during the intravitreal injection procedure. METHODS: Thirty patients (n=30) received topical ketorolac 0.5% or vehicle on subsequent intravitreal drug administrations. The procedure followed for the intravitreal injections was the same for all subsequent administrations with the use of tetracaine 0.5% drops as anesthetic. Ketorolac or vehicle was instilled before the injection, and pain perception was recorded on a 0 to 100 Visual Analog Scale (VAS) immediately after the intravitreal administration. RESULTS: Mean VAS pain score was 8.16±1.3 when patients received ketorolac and 12.33±1.41 when they received placebo, a difference that was statistically significant (P=0.0003) (paired t-test). CONCLUSIONS: Topical ketorolac 0.5% reduces patients' pain perception during intravitreal drug administration.

Subconjunctival bevacizumab for corneal neovascularization secondary to topical anesthetic abuse.

We report the clinical course of a 56-year-old patient diagnosed with toxic keratopathy due to topical anesthetic abuse. One month later, while a large corneal epithelial defect persisted, the cornea developed circumferential neovascularization that was treated with subconjunctival bevacizumab. Corneal neovascularization (CN) showed a dramatic regression 1 week after subconjunctival injection of bevacizumab. The epithelial defect slowly healed, no complications were observed, and no recurrence observed after 4 months of follow-up. In conclusion, bevacizumab may be valid complementary treatment in patients with CN secondary to topical anesthetic abuse. To our knowledge, this is the first case of CN due to topical anesthetic abuse benefiting from treatment of subconjunctival bevacizumab.

Effect of a fixed brimonidine-timolol combination on intraocular pressure after phacoemulsification.

PURPOSE: To evaluate the effect of a fixed combination of brimonidine-timolol on intraocular pressure (IOP) after phacoemulsification cataract surgery. SETTING: Department of Ophthalmology, Patras University Hospital, Patras, Greece. DESIGN: Prospective randomized comparative case series. METHODS: Patients scheduled for phacoemulsification were randomly assigned to 1 of 2 groups. The treatment group received 1 drop of brimonidine-timolol fixed combination immediately after surgery, and the control group received no treatment. The IOP was measured preoperatively and 6, 12, and 24 hours postoperatively. RESULTS: The treatment group comprised 28 eyes and the control group, 30 eyes. The mean IOP increased by 0.14 mm Hg ± 3.88 (SD) (P = .88) in the treatment group and increased by 2.8 ± 5.01 mm Hg (P = .007) in the control group. Twelve hours after surgery, the mean IOP decreased by -0.57 ± 3.82 mm Hg (P = .49) in the treatment group and increased by 2.20 ± 4.56 mm Hg (P = .009) in the control group. Twenty-four hours after surgery, the mean IOP decreased by -1.57 ± 2.30 mm Hg (P=.012) in the treatment group and increased by 0.86 ± 4.21 mm Hg (P = .175) in the control group. The mean IOP change between the 2 study groups 6, 12, and 24 hours postoperatively was statistically significantly different (P = .015, P = .006, and P = .003; respectively). CONCLUSION: The fixed brimonidine-timolol combination effectively reduced IOP 6, 12, and 24 hours after phacoemulsification cataract surgery.

Decreased contrast sensitivity in children and adolescents with type 1 diabetes mellitus.

PURPOSE: To evaluate contrast sensitivity in children and adolescents with diabetes mellitus without evidence of diabetic retinopathy. METHODS: Sixty patients with insulin-dependent diabetes mellitus (age range: 8 to 18 years) were studied. Their contrast sensitivity scores were obtained using the CSV-1000 device (Vector Vision, Dayton, OH) for four spatial frequencies and were compared with v scores of 45 age-matched and gender-matched "healthy" patients. Contrast sensitivity values were also correlated to patient's age, duration of disease, and metabolic control of diabetes mellitus. RESULTS: The patients with insulin-dependent diabetes mellitus had a significant contrast sensitivity score reduction at all spatial frequencies tested. Glycosylated hemoglobin levels were inversely related to the contrast sensitivity thresholds. No significant correlation was found between the contrast sensitivity scores and the patient's age or duration of disease. CONCLUSION: Contrast sensitivity defects are detected in patients with insulin-dependent diabetes mellitus. These defects may represent an early dysfunction of the retina, visual pathway, or both in patients with insulin-dependent diabetes mellitus who do not show any signs of diabetic retinopathy.

Pars plana vitrectomy in the treatment of severe complicated toxoplasmic retinochoroiditis.

PURPOSE: To present the anatomic and functional results of pars plana vitrectomy performed in severe complicated toxoplasmic retinochoroiditis. METHODS: Three patients, 2 women and 1 man aged 57, 22, and 57 years, are presented. The first patient was under immunosuppressive therapy for dermatomyositis and underwent diagnostic/therapeutic vitrectomy for severe toxoplasmic panuveitis with dense vitritis. The other 2 patients underwent vitrectomy for macula-off rhegmatogenous retinal detachment that developed after severe toxoplasmic panuveitis. RESULT: Preoperative visual acuity was hand movement for the first 2 patients and 20/400 for the third. All patients received pars plana vitrectomy with epiretinal membrane peeling, laser photocoagulation, and SF6 gas tamponade. The second and third patients needed 5 and 3 additional operations, respectively, including extensive retinotomies and silicone-oil tamponade, for recurrent retinal detachment due to proliferative vitreoretinopathy. At the end of the follow-up period (11, 5, and 1 year, respectively), the retina was attached and visual acuity was 20/30 for the first patient but counting fingers for the other 2 patients. CONCLUSIONS: Severe panuveitis and/or recurrent retinal detachment may develop in some cases of ocular toxoplasmosis, compromising the visual prognosis. Retinal detachment due to toxoplasmosis is generally complex, and long-acting tamponade with silicone oil should be contemplated for anatomic retinal reattachment.

Periorbital and orbital cellulitis: a 10-year review of hospitalized children.

PURPOSE: Periorbital cellulitis is often difficult to distinguish from orbital cellulitis, which is a potentially lethal infection involving the contents of the orbit. A delay in diagnosis and appropriate treatment may result in serious complications. We studied the predisposing factors, microbiologic data, clinical features, complications, and treatment of periorbital and orbital cellulitis in childhood. METHODS: Eighty-three medical records of patients (mean age 3.7 ± 3.1 years) admitted to the Department of Pediatrics with a diagnosis of periorbital or orbital cellulitis during the 10-year period January 1997 to December 2007 were retrospectively studied. RESULTS: In this series, periorbital cellulitis occurred more frequently (83%) than orbital cellulitis (17%). Of the children with periorbital cellulitis, 85% were younger than 5 years of age, while 62% of the children with orbital cellulitis were older than 5 years of age. The most common predisposing factors in periorbital cellulitis were upper respiratory infection (68%) and trauma to the eyelids (20%), while sinusitis was more frequently associated with orbital cellulitis (79%). Blood and skin cultures were usually negative. The most common isolated pathogens were Staphylococcus aureus, Streptococcus pneumoniae, and Staphylococcus epidermidis. Forty-five of the 83 children were treated with intravenous ceftriaxone + clindamycin (mean duration 8.6 ± 5.5 days). Intravenous antibiotics alone was an effective management in most of the patients, but a small proportion (6%) required surgical intervention. CONCLUSIONS: Upper respiratory infection and sinusitis are the most important predisposing factors for periocular infection. Streptococcus species are the predominant causative agents. Both diseases can usually be successfully treated with intravenous antibiotics, but some patients may require surgery to control extensive infection.

Tear analysis of ascorbic acid, uric acid and malondialdehyde with capillary electrophoresis.

Tears have a significant role in antioxidant defense in ocular tissues and since their collection is quick and noninvasive, their analysis would facilitate monitoring of pathophysiological changes. However, their low volume and low content of antioxidants makes analysis difficult; methods of high sensitivity are needed. In this paper, we present a method for tear analysis of two antioxidant molecules (ascorbic and uric acid) and of a lipid peroxidation indicator (malondialdehyde) with capillary electrophoresis. Tears were collected with Schirmer strips, extracted with a low-pH phosphate buffer, centrifuged through membrane filters and an antioxidant was added. They were stable at -70 degrees C for 15 days. After pilot experiments, optimum electrophoretic separation was achieved in a 25 mM borate buffer, pH 10.0, containing 100 mM sodium dodecyl sulfate at 25 degrees C and 20 kV. The developed method has good repeatability (<5% RSD), precision (<15% relative error values) and high sensitivity (LLOQ values of 20, 2.3 and 2.5 microM for ascorbate, urate and malondialdehyde, respectively). It was applied to the analysis of tears from healthy individuals and the antioxidant levels are in agreement with those obtained with other techniques. This method might serve as a tool to clarify the role of endogenous antioxidants in the pathophysiology of ocular diseases.

Complement factor H and LOC387715 gene polymorphisms in a Greek population with age-related macular degeneration.

BACKGROUND: Age-related macular degeneration (AMD) is the leading cause of severe visual loss among people over 60 years old. The lack of a broadly effective treatment for AMD underscores the need to identify causative biomarkers that could serve as preventive targets. Thus far, two major susceptibility loci for AMD have been identified, CFH T1277C and LOC387715 G270T. The primary goal of the present study was to elucidate whether these polymorphisms are major genetic determinants of AMD in a Greek population. PATIENTS AND METHODS: A clinic-based, case-control association study was conducted, comprising 100 Greek patients with early and late-stage AMD and 115 independent controls of Caucasian origin. All participants underwent clinical examination including best-corrected visual acuity, intraocular pressure, and dilated fundus examination. Moreover, they were genotyped for CFH T1277C and LOC387715 G270T polymorphisms, by direct sequencing and ARMS PCR, respectively. RESULTS: The frequency of the CFH 1277C allele was significantly higher in AMD patients in comparison with controls while the odds ratios (ORs) for AMD were 4.4-5.5. Statistical comparison of early and advanced AMD patients, on the basis of CFH genotype, revealed that the CFH 1277C allele was associated with both subgroups when compared with the controls (P < 0.001). When statistical comparison was performed between early and advanced patients on the basis of CFH genotypic frequencies, the CC genotype was found to be more prevalent in advanced AMD patients (P = 0.008, OR = 2.3). The frequency of the LOC387715 270 T allele was higher in AMD patients in comparison with controls (P < 0.04) while the ORs for AMD were 1.4-2. No statistically significant differences were located between the early AMD patients and controls, on the basis of LOC387715 genotype (P = 0.189). On the contrary, the T270G polymorphism was associated with advanced AMD (P = 0.04). Moreover, the TT genotype was more prevalent in patients with advanced AMD (P = 0.011, OR = 1.7) when compared with early AMD patients. Assessment of the combined contribution of CFH T1277C and LOC387715 G270T SNPs showed an independent manner of action of these polymorphisms in the development of the disease. CONCLUSIONS: The replication of the reported associations of CFH T1277C polymorphism with AMD suggest that the 1277C allele could serve as a high-risk genetic marker for the development of AMD and the progression of the disease to the advanced clinical stage in the Greek population.