The effects of bevacizumab treatment in a rat model of retinal ischemia and perfusion injury.

Purpose: To create a model of an ischemic retina with temporary ischemia and reperfusion (IR) and to examine the possible antiapoptotic and neurodegenerative effects of a vascular endothelial growth factor (VEGF) antagonist. Methods: Three groups were formed. Rats were subjected to continued ischemia for 45 min, and then reperfusion was allowed for 2 days. For the first group, ischemia was induced, but an anti-VEGF agent was not administered. For the second group, 2 days before ischemia, 0.005 ml (0.125 mg) of bevacizumab was administered intravitreally, and then the ischemic model was created. The last group's intraocular pressure was not increased as in the control group, and only a cannula was introduced into the anterior chamber through the cornea. Six animals from each group were subjected to histomorphometry, and four were subjected to immunohistochemical and histopathologic examinations. For a histomorphometric examination, the number of cells in the retinal ganglion cell (RGC) layer was counted using the optical dissector method. For immunohistochemistry, the vascular endothelial growth factor receptor-2 (VEGFR-2) levels and apoptosis were examined in the retinal and choroidal tissue. Results: It was observed that in an IR injury, bevacizumab reduces the death and apoptosis of cells in the RGC layer. It was also identified that although bevacizumab is a large molecule, the agent affects the choroid and reduces the amount of VEGFR-2 in this tissue. Conclusions: IR may be used as a model of ischemic retinopathy that includes VEGF-dependent vascular permeability and neurodegeneration. Although VEGF is a neurotrophic molecule, in IR injury, treatment with bevacizumab, which is an anti-VEGF agent, decreases apoptosis, showing that excess function of this molecule can be hazardous.

Fundus Findings in Dengue Fever: A Case Report.

Dengue fever is a flavivirus infection transmitted through infected mosquitoes, and is endemic in Southeast Asia, Central and South America, the Pacific, Africa and the Eastern Mediterranean region. A 41-year-old male patient had visual impairment after travelling to Thailand, which is one of the endemic areas. Cotton wool spots were observed on fundus examination. Fundus fluorescein angiography showed minimal vascular leakage from areas near the cotton wool spots and dot hemorrhages in the macula. Dengue fever should be considered in patients with visual complaints who traveled to endemic areas of dengue fever.

Comet Lesions in Patients with Pseudoxanthoma Elasticum.

Pseudoxanthoma elasticum (PXE) is a genetic multisystemic disorder affecting the skin, eyes and cardiovascular system. Basic fundoscopic findings in PXE result from Bruch's membrane involvement. The most important fundoscopic findings are angioid streaks. Other significant ocular findings are peau d'orange appearance, optic disc drusen, pattern dystrophy-like macular appearance, comet lesions, and choroidal neovascularization. Comet lesions are a pathognomonic ocular finding for PXE. The presence of both angioid streaks in the fundus and typical skin lesions should alert clinicians to PXE. Herein, we present two PXE cases with comet lesions.

Microbubble in the hole: a rare cause of failed macular hole surgery?

PURPOSE: To present a failed macular hole surgery with gas microbubble retention within the hole. METHODS: A 68-year-old female patient with a Stage 2 macular hole underwent vitrectomy with removal of posterior hyaloid and 12% C3F8 gas injection. Because the macular hole was Stage 2 and posterior hyaloid was observed to be firmly attached over the macular area, no attempt was made for peeling of internal limiting membrane. Postoperatively, the patient was instructed to keep a facedown posture for 1 week. At 1-month visit, ophthalmoscopy revealed a tiny gas bubble filling the macular hole that failed to close. RESULTS: The patient underwent a repeat vitrectomy in which internal limiting membrane was peeled, and the eye was filled with 20% SF6. At 2-week follow-up visit, the hole was observed to be closed. CONCLUSION: The reason for the macular hole nonclosure in this case may be the lack of internal limiting membrane peeling in the first operation. However, the authors believe that microbubble localized within the hole might have contributed to the failure.

Short-term effects of a single intravitreal bevacizumab injection on retinal vessel calibre.

PURPOSE: The aim was to investigate the short-term effects of a single intravitreal bevacizumab injection on the retinal vessel calibre in patients with neovascular age-related macular degeneration and in patients with diabetic macular oedema. METHODS: Twelve patients with neovascular age-related macular degeneration and eight patients with diabetic macular oedema were included in the study. All patients received an intravitreal injection of 1.25 mg bevacizumab. Red-free fundus photographs (35°) were acquired with a fundus camera at baseline and one day, one week and one month after the intravitreal injection. Measurements of retinal vessel diameter were made of the supero-temporal retinal venule and arteriole using the software available on the IMAGEnet program. RESULTS: Although there appeared to be a trend towards vasoconstriction for the measurements in the diabetic macular oedema group (both for arterioles and venules at day 7) and the age-related macular degeneration group (for venules at day 1 and for arterioles at day 7), it did not reach statistical significance (p > 0.05). Optical coherence tomography revealed a significant decrease in foveal thickness measurements in both groups at the one month visit compared with baseline. CONCLUSION: The results suggest that intravitreal injection of bevacizumab might induce retinal vasoconstriction; however, low numbers of subjects might have prevented the difference from reaching statistical significance. Further studies with a larger number of subjects would reveal the effect of intravitreal anti-vascular endothelial growth factor treatment on retinal vessel diameters more clearly.

Fundus autofluorescence in acute and chronic central serous chorioretinopathy.

BACKGROUND: A prospective evaluation of the pattern of fundus autofluorescence in cases of acute versus chronic central serous chorioretinopathy (CSR). METHODS: A prospective, cross-sectional, single-centre investigation was performed using three diagnostic techniques, namely, fundus autofluorescence, optical coherence tomography and fundus fluorescein angiography to evaluate a sample of patients (n = 42 eyes) with both acute (n = 25 eyes) and chronic (n = 17 eyes) CSR. RESULTS: Hypoautofluoresecence was found in 80 per cent (20 eyes) and 88.2 per cent (15 eyes) of eyes in the acute and chronic central serous chorioretinopathy groups, respectively, corresponding to the leakage points depicted by fluorescein angiography. Hypoautofluoresence corresponding to the areas of subretinal fluid accumulation was seen in 92 per cent (23 eyes) and 82.3 per cent (14 eyes) of the acute and chronic central serous chorioretinopathy groups, respectively. In two eyes (11.6 per cent) with chronic CSR, hyperautofluorescent changes were noted at the previous leakage points. In the acute CSR group, speckled hyperautofluorescence was detected in nine eyes (36 per cent) after the resolution of subretinal fluid. In the chronic CSR group, simultaneous speckled hyperautofluorescence was detected in the previous areas of subretinal fluid accumulation in 12 eyes (70.5 per cent). CONCLUSION: Fundus autofluorescence imaging delineates endogenous fluorescence derived mainly from lipofuscin within the retinal pigment epithelium (RPE) layer and therefore permits evaluation of functional alterations in the RPE in numerous retinal diseases. Data from fundus autofluorescence revealed distinctive findings in acute and chronic CSR. Fundus autofluorescence imaging may be used as a supplementary diagnostic tool for identifying patients with CSR and differentiation may be made between acute and chronic cases.

Polymorphisms of the DNA repair genes XPD and XRCC1 and the risk of age-related macular degeneration.

PURPOSE: Oxidative stress seems to be an important factor in the development of age-related macular degeneration (AMD). The role of DNA repair mechanisms has also received attention recently in AMD pathogenesis. This case-control study was conducted to determine the frequency of polymorphisms in two DNA repair enzyme genes, xeroderma pigmentosum complementation group D (XPD), codons 312 and 751, and x-ray cross-complementing group 1 (XRCC1), codons 194 and 399, in patients with AMD and in disease-free control subjects. METHODS: Polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) were used to analyze XPD Asp312Asn and Lys751Gln and XRCC1 Arg194Trp and Arg399Gln in 120 patients with AMD (65 with dry type and 55 with wet type) and in age-matched 205 disease-free control subjects. RESULTS: Genotypic and allelic distributions of the polymorphisms were detected. For the XPD polymorphism, although the allele frequencies were not different between the patients and healthy control subjects, there was a significant difference between frequencies for the XPD751 Gln/Gln genotype in AMD patients (9%) and healthy control subjects (19%; P=0.02). The XPD751 Gln/Gln genotype seemed to have a protective effect against development of AMD (odds ratio, 0.41; 95% confidence interval, 0.19-0.88). Stratification by subtype of AMD revealed that the XPD751 Gln/Gln genotype was significantly lower only in the patients with dry type (P=0.02). These interactions remained nearly significant after Bonferroni correction (P<0.0125). Haplotype analysis for the two XPD polymorphisms revealed that the haplotype GC (312Asp-(751)Gln) was a protective haplotype against AMD. No statistically significant difference was found for the genotypic and allelic distributions of the polymorphisms in the XRCC1 gene between the patients and the control subjects. CONCLUSIONS: Polymorphism in XPD codon 751 may be associated with the development of AMD.

A randomized, double-masked controlled clinical trial of Sandostatin long-acting release depot in patients with postsurgical cystoid macular edema.

PURPOSE: The purpose of this study was to evaluate the safety and efficacy of octreotide, a somatostatin analog, for treatment of postsurgical cystoid macular edema. METHODS: Twenty-one patients with chronic, refractory postsurgical cystoid macular edema and Early Treatment Diabetic Retinopathy Study best-corrected visual acuity of 20/25 to 20/400 were randomized 2:1 to 30 mg monthly intramuscular octreotide or placebo. Outcome measures were visual acuity (primary) and macular thickness and fluorescein angiographic leakage (secondary). RESULTS: Fourteen eyes received octreotide and seven eyes received placebo. Mean duration of cystoid macular edema was 2.65 and 1.99 years for Sandostatin long-acting release and placebo groups, respectively. Visual acuity at 6 months improved > or =2 lines in 7 of 14 eyes (50%) in the treatment group and 0 of 7 eyes in the placebo group (P = 0.046). Improvement in retinal thickening and angiographic leakage occurred in 3 of 13 eyes (23.1%) and 3 of 14 eyes (21.4%) of the treatment group, respectively, and in 1 of 7 eyes (14.3%) (P = 1.0 compared with the treatment group) and 0 of 7 eyes in the placebo group (P = 0.52 compared with the treatment group). The three eyes that improved in all parameters were treated with octreotide. CONCLUSION: Although there were no statistically significant differences between both groups in retinal thickening or angiographic leakage, octreotide-treated patients were more likely to experience a > or =2-line improvement in visual acuity. However, this observation cannot be generalized because of the small sample size.

Correlation of retinal sensitivity and retinal thickness in central serous chorioretinopathy.

AIM: To evaluate the correlation of microperimetry (MP) and optical coherence tomography (OCT) in eyes having acute onset of central serous chorioretinopathy (CSCR). METHODS: After a detailed ophthalmological examination, all cases were evaluated by fundus fluorescein angiography, OCT and MP. Mean macular thickness was detected by OCT. Mean macular sensitivity (MS) and mean defect (MD) were determined by MP. The correlation between OCT and MP findings was analyzed by Spearman's correlation test. RESULTS: Fifteen eyes with CSCR of 15 patients with a mean age of 40.5 +/- 6.7 years were recruited. The mean visual acuity was 0.7 +/- 0.2, and the mean macular thickness was 348.9 +/- 75.8 mum. Mean MS and MD were 13.9 +/- 4.6 and -5.2 +/- 4.1 dB, respectively. The mean macular thickness was significantly correlated with both mean MS and MD (p = 0.011 and p = 0.017, respectively). A significant correlation was also found between mean macular thickness, MS and MD in the central 1 mm, superior 3 mm and nasal 3 mm of the macula (p < 0.05). CONCLUSIONS: Our results demonstrated a significant correlation between structural and functional changes in CSCR. MP provides quantitative measurements of central macular function in CSCR that may supplement OCT findings as well as the better understanding of visual functions during the acute stage of the disease.

HLA-B51 gene and its expression in association with Behçet's Disease in Denizli Province of Turkey.

Behçet's Disease (BD) is a multisystemic inflammatory disorder as a triad of symptoms including recurrent oral and genital aphthous ulceration, and uveitis with unknown pathogenesis. Many researchers have tried to investigate the association of HLA-B51 gene with the BD. We aimed to investigate the association of the HLA-B51 gene and its expression, also polymorphic structure by PCR, RT-PCR and sequence specific oligonucleotide primers and probes in BD patients (n: 35) and control group (n: 50). According to our results, we did not observe any association in between HLA-B51 gene, its polymorphism, expression and BD patients.

Intraobserver repeatability of automated versus adjusted optical coherence tomography measurements in patients with neovascular age-related macular degeneration.

AIM: To assess the intraobserver repeatability of automated versus adjusted optical coherence tomography (OCT) measurements in patients with neovascular age-related macular degeneration (NVAMD). METHODS: Ten eyes with NVAMD from 10 consecutive patients underwent two OCT measurements within 5 days by a single operator. Automated and adjusted central 1-mm foveal thickness and automated and adjusted total macular volume were measured in each study eye. The term 'adjusted' refers to manually corrected values, in which the interface landmarks for measurements are selected by the operator using Stratus scan profiling and custom software. Bland-Altman method and bootstrap comparison of intraclass correlations (ICCs) were used for repeatability analysis. RESULTS: Bland-Altman comparison did not reveal any statistically significant difference in any parameter, when results at first and second examination were compared (p > 0.05), indicating that the repeated measurements are similar. Further analysis was conducted using the bootstrap comparison of ICCs. The difference between adjusted and automated foveal thickness ICCs (r = 0.945 and 0.635, respectively) was significant (p = 0.031), indicating higher repeatability for adjusted foveal thickness. The ICCs for adjusted and automated total macular volume (r = 0.873 and 0.863, respectively) showed no statistically significant difference (p = 0.881). CONCLUSION: The repeatability of adjusted retinal thickness measurements, in which the errors of retinal boundary detection by OCT analysis software is corrected by the operator using scan profiling, is found to be higher than that of automated ones in this small group of NVAMD patients when performed by a single experienced operator.

Optical coherence tomography features of sub-internal limiting membrane hemorrhage and preretinal membrane in Valsalva retinopathy.

CASE REPORT: Optical coherence tomography features of a sub-internal limiting membrane (ILM) premacular hemorrhage and dome-shaped preretinal membrane secondary to Valsalva retinopathy are described. COMMENTS: The origin of the membrane (internal limiting membrane or posterior hyaloid) and the location of the blood (sub-ILM or subhyaloid) are difficult to define by ophthalmoscopy.

Orbital color Doppler imaging in Behçet's disease with or without ocular involvement.

PURPOSE: To investigate the value of color Doppler imaging (CDI) of orbital vasculature in the assessment of ocular involvement in patients with Behçet's disease (BD) without clinical ophthalmologic abnormalities. METHODS: CDI of the orbital vessels were performed on 26 eyes of 13 patients who were diagnosed as having BD with ocular involvement (group 1), 65 eyes of 33 patients who had BD without ocular involvement (group 2) and 40 eyes of 20 healthy volunteers (group 3). Peak systolic (PSV) and end-diastolic (EDV) blood flow velocities and resistivity index (RI) measurements were obtained for the ophthalmic artery (OA) and central retinal artery (CRA). The mean velocity of the central retinal vein (CRV) was also measured. RESULTS: For the OA, PSV and EDVs were significantly lower and RIs were significantly higher in group 2 than in control subjects. In group 1, only the EDVs of OA were significantly lower than in healthy subjects. For the CRA, PSV and EDVs were significantly lower, and RIs were significantly higher in both BD groups than those in group 3. When group 1 and group 2 were compared, the differences between PSV, EDV and RI measurements for the CRA and OA were statistically insignificant. There was no significant difference in blood flow velocity of the CRV between the three groups. CONCLUSION: Major hemodynamic changes were observed in the ophthalmic vasculature of Behçet's patients with or without ocular involvement by CDI. CDI may detect ocular blood flow alterations before initial clinical manifestations.

Dynamic and quantitative analysis of choroidal neovascularization by fluorescein angiography.

PURPOSE: In this study, the authors sought to develop and characterize techniques for measuring changes in choroidal neovascularization (CNV) lesion size and fluorescence over time for quantitative analysis of fluorescein angiograms. METHODS: Initial assessment of the quantitative technique was made by retrospectively analyzing digital fluorescein angiograms taken before and 3 months after photodynamic therapy (PDT) for CNV (6 patients, group 1). The method was then applied prospectively to digital fluorescein angiograms (baseline and day 71) obtained on 12 patients taking part in a clinical trial investigating the effect of vascular endothelial growth factor (VEGF) Trap in CNV (group 2). Two masked observers, with the use of image processing, measured the area of hyperfluorescence and fluorescence intensity above background. Values for each image were plotted against time after dye injection to generate curves, and each area under the curve (AUC) was calculated. RESULTS: The physician who treated the patients in group 1 judged the condition of three patients to be improved and of three to be worse 3 months after PDT. Masked retrospective grading of fluorescein angiograms showed an 11% decrease in AUC for fluorescence area and a 32% decrease in AUC for fluorescence intensity in the three patients whose conditions clinically improved but increases of 131% and 292% in the three patients whose conditions clinically worsened. In group 2, a 38% decrease in AUC for fluorescence intensity and a 19% decrease in AUC for fluorescence area were observed in patients who received VEGF Trap compared with increases of 66% (P = 0.004, Mann-Whitney U test) and 21% (P = 0.07) for patients who received placebo. Macular volume decreased by 11% in VEGF Trap-treated patients and increased by 10% in placebo-treated patients (P = 0.03). CONCLUSIONS: This study reports a technique for analysis of change in fluorescence area and intensity over time during fluorescein angiography (FA) using a continuous scale and its application in a clinical setting and a clinical trial. Compared with previous techniques making use of categorical scales, this approach provides an advantage for evaluating responses to treatment that may improve the value of FA as an outcome measure in clinical trials.

Vascular endothelial growth factor is a critical stimulus for diabetic macular edema.

PURPOSE: The role of vascular endothelial growth factor (VEGF) in diabetic macular edema (DME) was tested with ranibizumab, a specific antagonist of VEGF. DESIGN: A nonrandomized clinical trial. METHODS: Ten patients with chronic DME received intraocular injections of 0.5 mg of ranibizumab at baseline and at one, two, four, and six months. The primary outcome was change in foveal thickness between baseline and seven months, and the secondary outcome measures were changes from baseline in visual acuity and macular volume. RESULTS: Mean values at baseline were 503 microm for foveal thickness, 9.22 mm3 for macular volume, and 28.1 letters (20/80) read on an Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity chart. At seven months (one month after the fifth injection), the mean foveal thickness was 257 microm, which was a reduction of 246 microm (85% of the excess foveal thickness present at baseline; P = .005 by Wilcoxon signed-rank test for likelihood that this change is due to ranibizumab rather than chance). The macular volume was 7.47 mm3, which was a reduction of 1.75 mm3 (77% of the excess macular volume at baseline; P = .009). Mean visual acuity was 40.4 letters (20/40), which was an improvement of 12.3 letters (P = .005). The injections were well-tolerated with no ocular or systemic adverse events. CONCLUSION: Intraocular injections of ranibizumab significantly reduced foveal thickness and improved visual acuity in 10 patients with DME, which demonstrated that VEGF is an important therapeutic target for DME. A randomized, controlled, double-masked trial is needed to test whether intraocular injections of ranibizumab provide long-term benefit to patients with DME.

Effects of intraoperative sponge mitomycin C and 5-fluorouracil on scar formation following strabismus surgery in rabbits.

PURPOSE: To investigate the influence of 5-fluorouracil (5-FU) and mitomycin C (MMC) on the postoperative adhesions following strabismus surgery in rabbits. METHODS: Twenty-one New Zealand white rabbits were used in this prospective, masked, controlled trial. Both eyes of 20 animals underwent 3-mm recession of the superior rectus muscle (SRM). In group I (io animals), one eye of each animal received topical application of MMC (0.2 mg/ml) for 5 minutes and the other eye (control eye) was treated with balanced salt solution (BSS) using an intraoperative sponge. In group II (10 animals), a randomly chosen eye of each animal was treated with 5-FU soaked sponges (50 mg/ml) for 5 minutes and the fellow eye (control eye) with BSS. Two eyes of a rabbit were included as unoperated controls. Four weeks after the surgery, conjunctival vascularity and postoperative adhesions between the SRM Tenon's capsule (TC) and SRM sclera (scl) were assessed. Additionally, eyes were enucleated and evaluated histopathologically for evidence of scarring, granuloma formation, and muscle tissue changes under a light microscope. RESULTS: MMC-treated eyes had a higher rate of avascular conjunctiva compared to both controls and 5-FU-treated eyes. Mean adhesion scores, particularly between the SRM-scl, were lower in eyes treated with antiproliferative agents compared to controls. The difference was statistically significant in MMC-treated eyes for the adhesions between SRM-scl (p = 0.03). Histopathological examination revealed less scarring and granuloma formation in MMC- and 5-FU-treated eyes compared to their control eyes. CONCLUSIONS: MMC, and to a lesser extent 5-FU, are shown to be effective in reducing postoperative scarring following strabismus surgery in rabbits. It seems reasonable to suggest that antimetabolites should be used for cases having an increased risk of postoperative adhesions.

Efficacy and safety of rimexolone 1% versus prednisolone acetate 1% in the control of postoperative inflammation following phacoemulsification cataract surgery.

PURPOSE: The aim of this study was to evaluate the efficacy and safety of rimexolone 1% ophthalmic suspension compared to that of 1% prednisolone acetate in the control of inflammation in eyes undergoing cataract extraction with phacoemulsification followed by posterior chamber intraocular lens implantation. METHODS: Forty-eight patients who underwent uncomplicated cataract extraction with phacoemulsification followed by posterior chamber IOL implantation constituted the study group of this prospective, randomized, double-masked investigation. Patients were randomly assigned to two treatment groups; rimexolone 1% ophthalmic suspension (27 subjects) or prednisolone acetate 1% (21 subjects). Postoperatively, patients used topical rimexolone or prednisolone drops four times a day for 15 days. Patients were examined at the first postoperative day (day 1), and days 3, 7 and 15. The major efficacy parameters assessed clinically on each visit were anterior chamber cells, anterior chamber flare and conjunctival hyperemia. Safety of the rimexolone was evaluated by IOP values and the presence of adverse effects. RESULTS: Regarding all three efficacy parameters, rimexolone was found to be clinically and statistically equivalent to prednisolone acetate. Intraocular pressure values during the postoperative period were also similar in both groups. CONCLUSION: Rimexolone 1% ophthalmic suspension is both an effective and safe topical steroid in controlling postoperative inflammation after cataract extraction with phacoemulsification.

Hyperhomocysteinemia: a risk factor for retinal vein occlusion.

PURPOSE: The aim of the study was to investigate the plasma homocysteine levels in patients with retinal vein occlusion (RVO) in order to reveal whether hyperhomocysteinemia was a risk factor for RVO. METHODS: Thirty-three consecutive patients diagnosed to have RVO of any type and 25 age- and sex-matched controls without RVO were included in this prospective case-control study. Data regarding age, sex, history of hypertension, diabetes mellitus, other vascular events, glaucoma, medications and smoking habits were obtained from all subjects. Several laboratory tests relating to vascular disease including cholesterol, triglyceride and hematocrit were checked. The plasma total homocysteine (tHcy) level was measured by high-performance liquid chromatography (normal range: 5-15 micromol/l). Plasma folate, vitamin B(12) and creatinine levels were also studied since these vitamins and impairment of renal function might affect plasma tHcy values. RESULTS: Patients with RVO had a significantly higher tHcy level (median: 11.7 micromol/l, range: 7.2-25 micromol/l) compared to controls (median: 10.3 micromol/l, range: 6.7-13.4 micromol/l; p = 0.005). Nine of 33 patients with RVO (27.3%) had an elevated plasma tHcy level, whereas none of the controls had an abnormal tHcy value (p = 0.004). Plasma folate, vitamin B(12) and creatinine levels were comparable between the two groups (p > 0.05). CONCLUSIONS: The present study suggests an association between hyperhomocysteinemia and RVO. Further controlled studies with a large number of cases are needed to investigate the exact role of hyperhomocysteinemia in RVO.