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Purpose To evaluate the effects of intravitreal injection of tissue plasminogen activator (tPA) and gas vs. pars plana vitrectomy (PPV) surgery as first-line treatment for subretinal hemorrhage. Methods Retrospective study of 107 adults treated for subretinal hemorrhage at a tertiary hospital during 2008–2019; 51 received injection of tPA and gas and 56 underwent PPV. Results No between-group differences were found in age and sex, medical history, use of anticoagulants or antiplatelets, history of ocular surgeries, and previous use of intravitreal anti-VEGF. Overall follow-up time was longer in the PPV group (median 4.9 vs 3.28 years, p = 0.005). The hemorrhage was displaced in a similar percentage of patients in the tPA-and-gas group (n = 40, 78.4%) and the PPV group (n = 45, 80.4%) (p = 0.816). Approximately 80% of patients in the tPA-and-gas group were able to forgo PPV surgery. Visual acuity (in LogMAR) was similar in the two groups prior to the diagnosis of subretinal hemorrhage but better in the tPA-and-gas group at the end of follow-up (p Conclusion Injection of gas and tPA can be done immediately following diagnosis of subretinal hemorrhage as an office procedure. Visual acuity outcome is good, with a high rate of blood displacement. About 20% of patients might require additional PPV as secondary intervention.

Purpose To compare morphologic characteristics of type 1 macular neovascularization (MNV) flow pattern in treatment-naïve and previously treated patients with age-related macular degeneration (AMD) as assessed by optical coherence tomography angiography (OCTA). Study Design Cross-sectional study Materials and Methods Macular OCT angiography images were acquired using RTVue XR Avanti with AngioVue. Distinct morphologic biomarkers and quantifiable features of the neovascular membranes were studied on en-face projection images comparing treatment-naïve and previously treated patients. Results The study included 68 eyes of 58 patients. Among them, 24 eyes were treatment-naïve, and the remaining eyes had received a mean of 19.6 injections. Immature lesions were more associated with treatment-naïve eyes and hyper-mature lesions were associated with previously treated eyes (p = 0.005). Tangle pattern was associated with treatment-naïve eyes (p = 0.013), whereas mature core vessels and sea fan pattern were associated more with previously treated eyes (p = 0.001 and p = 0.044, respectively). Vascular density of the neovascular membrane was higher in the treatment-naïve group (p = 0.036) and the average MNV area was similar between the 2 groups (p = 0.683). Conclusions Based on OCTA, morphologic biomarkers of type 1 MNV might be an indication of previous treatment. The MNV pattern can improve our understanding of its maturation under anti-VEGF treatment and might be valuable to better guide therapeutic decisions and provide more personalized care to patients with AMD.

Lymphatic-venous malformations (LVMs) are development defects that result in abnormal connections between the lymphatic and venous systems. The authors describe a 7-weeks-old female infant who presented with a right orbital LVM extending to the ipsilateral cheek and subconjunctiva of the right eye, intracranial developmental venous anomalies in the right cerebellum, and a significant right eye intraocular retinal vascular malformation. Since orbital LVM is usually diagnosed in infancy or childhood, pediatric ophthalmologists should actively look for intraocular vascular malformations as such findings can poorly affect a patient’s vision.

Purpose To investigate the safety of face masks worn by patients during intravitreal injections. Methods A prospective, qualitative, interventional study performed in a tertiary university hospital. Healthy volunteers were asked to wear three different professional surgical face masks while air leaks around the eyes were monitored. Three types of masks were investigated as follows: 1) surgical face mask with four tying strips, 2) surgical face mask with elastic ear loops and 3) 2200 N95 tuberculosis particulate face mask. For each session the periocular area was inspected for air leak during normal respiration, speech, and deep respiration. Detection of air leak was performed using the following two professional thermal cameras: FLIR A310-thermal camera and EyeCGas 2.0-super sensitive infrared camera used for detection of minute fugitive emissions of industrial gases. Results Ten healthy volunteers were enrolled in this study. The experiment was repeated 45 times for each camera; 3 times for each of 3 mask types, on 5 volunteers, for a total of 90 trials. Air jets were detected originating from the superior edges of the masks radiating toward the eyes in 81% (73/90) of cases in total; 71% (32/45) with the FLIR camera and 91% (41/45) with the OPGAL camera. Air leaks were detected with all investigated mask types. Conclusion Patients wearing face masks during intravitreal injections may be at a higher risk of endophthalmitis. Until further data are available, we recommend verifying proper face mask fitting and either taping the upper edges of the face masks with a medical adhesive tape or using an adhesive surgical drape around the injected eye.

Objectives Our aim is to evaluate the safety, efficacy, predictability, and clinical outcome of femtosecond laser-assisted in situ keratomileusis (FS-LASIK) procedures performed on the day of the initial consultation relative to procedures performed at subsequent visits. Methods A retrospective cohort study design was used. The study group included patients with myopia of different severities who were treated with FS-LASIK in 2013 through 2014 in an optical outpatient clinic of a large private medical service. Inclusion criteria were at least 18 years of age, a stable refraction for 12 months, no history of autoimmune disease, ocular surgery, or eye disease, and complete medical records. Background, clinical, and outcome data were collected from the patient files. Results Femtosecond laser-assisted in situ keratomileusis was performed in 80 patients (160 eyes) at the first visit and 361 patients (719 eyes) at a subsequent visit. The mean±SD spherical equivalent (SE) refraction before surgery was -3.74±2.03 D in the first-visit group and -3.73±1.87 D in the subsequent-visit group (P=0.99). Efficacy index values were 0.97±0.15 in the first-visit group and 0.98±0.13 in the subsequent-visit group (P=0.92), and corresponding safety index values were 0.99±0.15 and 0.99±0.12 (P=0.81). The final SE measured -0.09±0.58 D in the first-visit group and -0.19±0.55 D in the subsequent-visit group (P=0.05). Types and rates of complications were similar in the two groups. Conclusions There is no significant difference in the results of refractive surgery with FS-LASIK between procedures performed at the initial or subsequent visits. In both conditions, FS-LASIK surgery is associated with excellent safety, efficacy, and predictability profiles.

Eye trauma is an unfortunate and often preventable cause of vision loss. Confetti cannons are common causes of injury. Awareness of ocular hazards of confetti cannons remains low because of limited reports describing ophthalmic injuries following their use.To describe outcomes of ocular trauma caused by confetti cannons and to increase recognition of their ocular risks.A retrospective analysis was conducted of eye injuries caused by confetti cannons presenting to a single medical center between 2016 and 2020. Data collected included age, gender, eye injured, ocular damage, visual outcome, and details of surgeries performed.Overall, six consecutive patients (2 males, mean age 19.5 ± 9.74 years) were identified and studied. In all patients only one eye was injured (3 right eyes) during a private celebration, most commonly (n=5) to a bystander while in the vicinity of a cannon operated by someone else. Most common eye injuries included corneal erosion (n=4), traumatic hyphema (n=4), and retinal edema (n=3). Mean initial logMAR visual acuity in the injured eye was 0.73 ± 0.18, improving to 0.25 ± 0.16 at the final visit (P = 0.125). Two patients underwent eye surgery due to their trauma: one to repair globe penetration and another to undergo intravitreal injection of tissue plasminogen activator and C3F8 for submacular hemorrhage, followed 8 months later by intravitreal bevacizumab injection for choroidal neovascularization.Confetti cannons pose hazards that can cause severe ocular trauma resulting in permanent vision loss. Increasing awareness of device hazards is necessary to prevent eye injuries.

Purpose: To evaluate the effect of velocity and angle of the intravitreal injection of anti-vascular endothelial growth factors on pain sensation.Methods: Patients were randomly assigned to one of four injection methods: straight and fast, straight and slow, tunneled and fast, and tunneled and slow. Later, they graded their pain sensation on a Visual Analog Scale (range 0-10).Results: The cohort included 180 patients. Mean pain score was 2.81 ± 2.34. There was no statistically significant difference in mean pain score among the four groups (p = .858); between the slow-injection (straight and tunneled) and fast-injection groups (p = .514); and between the straight-injection (fast and slow) and tunneled-injection groups (p = .992), nor other background variables.Conclusion: Velocity and angle of intravitreal injections are unrelated to the pain sensation. Therefore, the method may be left to the clinician's discretion. This implies that the sensation is mostly subjective.

PURPOSE To evaluate and correlate levels of various proteins involved in coagulation, inflammation and angiogenesis processes in the vitreous of patients with different vitreoretinal pathologies. METHODS Vitreous samples were collected from patients scheduled for pars plana vitrectomy for the treatment of rhegmatogenous retinal detachment (RRD), vitreous haemorrhage or tractional retinal detachment associated with proliferative diabetic retinopathy (PDR). Macular hole and epiretinal membrane served as controls. Levels of vascular endothelial growth factor, thrombin-antithrombin III complex, interleukin-8, tissue factor, thrombomodulin, P-selectin, D-dimer and tissue factor pathway inhibitor were compared among the vitreoretinal pathology groups. RESULTS Compared to controls, patients with PDR had significantly higher levels of thrombin-antithrombin III complex (p

PURPOSE: To evaluate the efficacy of intravitreal aflibercept as a second-line therapy in eyes with persistent diabetic macular oedema (DMO) despite receiving initial bevacizumab treatment. METHODS: A prospective multicentre study was conducted in nine academic clinics in Israel. Starting from the first follow-up visit, a treat-and-extend regimen was applied in which the treatment intervals were extended by 2 weeks based on macular thickness using SD-OCT. The primary outcome was central subfield thickness (CST) at week 52. RESULTS: Forty-four patients (n = 48 eyes) were recruited to the study, and 43 eyes completed 52 weeks of follow-up. Patients received a mean (±SD) of 7.9 ± 3.5 bevacizumab injections before enrolment. The mean (±SD) CST under aflibercept therapy decreased from 468 ± 131 μm at baseline to 303 ± 67 μm at 52 weeks (p = 0.002), and best corrected visual acuity improved from 64 ± 15 ETDRS letters at baseline to 75 ± 8 letters at week 52 (p = 0.001). Twenty (46%) eyes met the treat-and-extend criteria and received a mean (±SD) of 10.9 ± 2 aflibercept injections. CONCLUSIONS: Eyes with persistent DMO following initial bevacizumab therapy had a marked reduction in macular thickness and improved visual acuity following 1 year of treatment with intravitreal aflibercept. Less than half of the patients met eligibility criteria for extension of the treatment interval; for these patients, the treat-and-extend regimen resulted in a maximum treatment interval of 10 weeks during the first year.

PurposeThe purpose of this study is to evaluate an early switch to aflibecept in eyes with neovascular age-related macular degeneration (nvAMD) showing partial or lack of response for initial therapy with bevacizumab.MethodsThe Aflibercept as a Second Line Therapy for Neovascular Age Related Macular Degeneration in Israel (ASLI) was a prospective, multicenter, single-arm clinical trial. Eyes with nvAMD having incomplete response to 3-9 prior bevacizumab injections were recruited. Three monthly intravitreal aflibercept (2 mg) injections were administered, followed by two bi-monthly injections and a final examination at week 28. An optional injection was allowed at week 20.ResultsForty-seven eyes of 46 patients (mean±SD age 76±8 years) were recruited. The mean number of prior bevacizumab injections was 5.5±2.9. The mean visual acuity improved from 60.3±10 ETDRS letters at baseline to 63.1±15 letters at week 28 (P=0.02, paired t-test). The central subfield thickness (CST) reduced from 409±127 micron at baseline to 330±110 microns at week 4 (P=0.0002; paired t-test), and 277±70 microns at week 28 (P=0.00002; paired t-test). Twenty-two eyes had three to five prior bevacizumab injections (mean 5.1±0.7), and 25 eyes had six to nine prior injections (7.32±1.2). Both groups had reduced CST from baseline to week 28 (P=0.0004 and P=0.0007; paired t-test, respectively). Thirty-five (75%) eyes required the optional additional aflibercept injection at week 20.ConclusionsThe ASLI study demonstrated improved BCVA and reduced CST following an early switch to aflibercept therapy in eyes with prior incomplete response to initial therapy with three to nine bevacizumab injections.

Antivascular endothelial growth factor (Anti-VEGF) agents have been widely used for a variety of ocular disorders. The etiology of sustained ocular hypertension following intravitreal administration of anti-VEGF agents is yet to be unraveled. Our study investigates and characterizes the presence of intravitreally injected bevacizumab in the aqueous outflow channels of a rat model. Choroidal neovascularization (CNV) was induced by diode laser photocoagulation to the right eye of twelve Brown Norway rats. Bevacizumab (25 mg/ml) was injected intravitreally after 3 days. Immediately after bevacizumab injection, and 3, 6, 24 and 48 h later, animals were euthanized for immunofluorescence staining. Donkey anti-human IgG labeled with Alexa Fluor(®) 488 was used for bevacizumab immunoreactivity detection. Anti-CD31 antibody was used as a marker for Schlemm's canal endothelial cells. Untreated eyes were used as negative controls. The intensity of the immunostaining was analyzed qualitatively. Bevacizumab immunoreactivity was found in the aqueous outflow channels including the trabecular meshwork and Schlemm's canal immediately after injection, and declined incrementally within the following hours. Forty-eight hours after the injection, no bevacizumab staining was detected in the aqueous outflow channel structures. Our manuscript demonstrates the presence of bevacizumab in the trabecular meshwork and Schlemm's canal structures after intravitreal injection in a CNV induced rat model. Bevacizumab molecules passed through the aqueous outflow channels within 48 h after intravitreal bevacizumab injection.

Purpose: To evaluate the outcome of second-line intravitreal ranibizumab treatment in eyes with diabetic macular edema having persistent edema following initial therapy with intravitreal bevacizumab. Methods: Diabetic macular edema treated with ranibizumab following bevacizumab failure in Israel was a retrospective, multi-center study. Consecutive eyes with persistent diabetic macular edema following at least three previous intravitreal bevacizumab injections prior to intravitreal ranibizumab, at least three-monthly intravitreal ranibizumab injections and at least 12 months of follow-up were included. Data collected included demographics, ocular findings, diabetes control, details of intravitreal bevacizumab and ranibizumab injections, and visual and anatomical measurements before and after intravitreal ranibizumab treatment. Results: In total, 202 eyes of 162 patients treated at 11 medical centers across Israel were included. Patients received a mean (±standard deviation) of 8.8 ± 4.9 intravitreal bevacizumab injections prior to the switch to intravitreal ranibizumab. A mean of 7.0 ± 2.7 intravitreal ranibizumab injections were given during the 12 months following the switch to intravitreal ranibizumab. The median central subfield retinal thickness (±interquartile range) by spectral-domain optical coherence tomography decreased from 436 ± 162 µm at baseline to 319 ± 113 µm at month 12 (p Conclusion: Switching from bevacizumab to ranibizumab in persistent diabetic macular edema was associated with anatomical improvement in the majority of eyes and ⩾2 lines of vision improvement in 22% of eyes.

Purpose: To investigate the response to intravitreal ranibizumab after failure of intravitreal bevacizumab in patients with diabetic macular edema (DME). Methods: Demographics, visual acuity (VA), central macular thickness (CMT), and HbA1C were retrospectively collected from DME patients treated with second-line intravitreal ranibizumab at a tertiary hospital in 2012-2013 and followed for at least 3 months. Results: Twenty-two patients (26 eyes) were included in the study, with a mean (±SD) age of 66 ± 8.1 years and followed for an average of 28.36 months. The mean number of intravitreal bevacizumab injections was 7.3 ± 2.8, and of intravitreal ranibizumab injections 5.11 ± 2.4. After 3 ranibizumab injections, 57% of eyes showed improvement in VA. The change in VA was statistically significant (p = 0.044) in those eyes where the pretreatment acuity for the second-line therapy was Conclusion: Intravitreal treatment with ranibizumab can be efficacious in eyes with DME that have failed to respond to bevacizumab.

BACKGROUND AND OBJECTIVE: To determine whether subretinal fluid drainage (SRF) using perfluorocarbon (PFC) during rhegmatogenous retinal detachment (RRD) repair reduces postoperative metamorphopsia. PATIENTS AND METHODS: Consecutive patients after RRD were evaluated for best-corrected visual acuity (BCVA), funduscopy, and metamorphopsia using M-CHARTS. Fundus autofluorescence and optical coherence tomography were performed. Clinical and operative data were collected. RESULTS: The cohort included 30 patients, of whom 11 (36.7%) underwent intraoperative PFC injection. Rates of macula-off RRD were similar in the two groups (54.5% and 47.4%, P = .705). No association was found between PFC injection and metamorphopsia score. Preoperative macula-off RRD was associated with significantly higher vertical and horizontal metamorphopsia scores than preoperative macula-on. BCVA was significantly worse in the patients with metamorphopsia (logMAR 0.15 vs. logMAR 0.04; P = .042) CONCLUSION: Intraoperative SRF drainage with PFC appears to have no beneficial effect on postoperative metamorphopsia. Metamorphopsia is associated with macular status. [ Ophthalmic Surg Lasers Imaging Retina . 2018;49:e263–e270.]

PURPOSE The concomitant use of triamcinolone acetonide (TA) at the completion of pars plana vitrectomy for the treatment of epiretinal membrane may speed up the anatomical and functional outcomes of surgery. We report the outcome of patients undergoing small-gauge vitrectomy for idiopathic epiretinal membrane peel with or without adjuvant TA therapy. DESIGN This is a retrospective, single-center case series. METHODS We included 75 eyes of 75 individual patients. Twenty-six patients (group A) had an adjuvant TA injection during surgery, whereas 49 patients (group B) were not injected. We assessed the patients for change in visual acuity (VA) and central macular thickness before and after surgery. RESULTS Group A had a mean logarithm of the minimum angle of resolution VA of 0.63 ± 0.33 and 0.51 ± 0.31 preoperatively and 3 months after surgery, respectively. Group B had a mean logarithm of the minimum angle of resolution VA of 0.47 ± 0.17 and 0.36 ± 0.17 preoperatively and 3 months after surgery, respectively. No significant difference was found between the groups in change of VA. The mean central macular thickness for groups A and B patients before surgery was 474.12 ± 120 μm and 445 ± 85 μm, decreasing to 369 ± 70 μm and 386 ± 60 μm at the final visit, respectively. The difference in macular thickness reduction between the groups was statistically significant. CONCLUSIONS Anatomical and functional improvement was found in both groups after surgery. Macular thickness was further reduced in the group of patients treated with adjuvant TA.

Retinopathy of prematurity (ROP), which develops due to abnormal retinal vascularization in premature babies, can lead to irreversible vision loss. B-scan ocular ultrasonography is a noninvasive examination which makes it possible to image the eye and orbit. Our purpose was to echographically assess the orbit of premature babies with and without retinopathy of prematurity (ROP), with a focus on the superior ophthalmic vein (SOV) which is normally not detected by orbital ultrasound. A prospective study design was used after approved by the local institutional review board. ROP was diagnosed by routine ophthalmoscopic exam. Orbital ultrasound was performed by a single experienced ophthalmologist and ultra-sonographer who was masked to the routine ROP screening results. The results of the ophthalmoscopic exam were compared to the orbital ultrasound findings. The study group was divided into those diagnosed with ROP and those not diagnosed with ROP and were found to be comparable by age and weight at the time of the US examination. The SOV was dilated in 21 of 22 eyes (95.4%) with ROP and in only 5 of 32 eyes (15.6%) without ROP. The present study suggests an association between ROP and dilatation of the SOV.

Purpose: To determine whether intravitreal unconjugated tissue plasminogen activator (tPA) (alteplase) can penetrate the intact neural retina and reach the subretinal space in an experimental model. Methods: This study was performed in 24 Sprague-Dawley rats aged 12 weeks. Under general anesthesia, the right eye was injected with either 0.75 μg of 3 μL tPA (14 rats; study group) or saline (10 rats, control group) into the vitreous. Animals were euthanized at 3, 24, and 48 h. The eyes were enucleated, and cryosections were prepared for immunofluorescence staining. Goat anti-tPA antibody was used to detect tPA. Results: In the study group, staining for tPA was detected in the deep retinal layers in all eyes. The staining was deeper and more intense at 3 and 24 h than at 48 h. There was no tPA staining in the retina of eyes injected with saline. Conclusions: This experimental study shows that unconjugated tPA administered into the vitreous is capable of penetrating the deep retinal layers and the subretinal space. These findings suggest that further clinical research is warranted on the benefits of intravitreal tPA in the treatment of submacular hemorrhage.

To study the efficacy and outcomes of short-term postoperative vitreoretinal tamponade with perfluorocarbon heavy liquid in patients with giant retinal tear.The study group consisted of 13 consecutive patients (13 eyes) who presented with giant retinal tear at a tertiary medical center in 2011-2015 and were treated with vitrectomy followed by short-term tamponade with perfluorocarbon heavy liquid. A minimum of 3 months' follow-up was required for inclusion. The medical charts were retrospectively reviewed for patient demographics, procedural specifics, anatomical attachment rates, pre- and postoperative visual acuity, and postoperative complications.The duration of perfluorocarbon tamponade ranged from 6 to 13 days (mean ± SD 10 ± 2 days). Follow-up time ranged from 3 to 44 months (mean ± SD 11 ± 11 months). Retinal reattachment was achieved intraoperatively in all patients. Repeated detachment with proliferative vitreoretinopathy occurred in one patient (8%), who underwent repeated vitrectomies. At the last follow-up visit, the retina was attached in all patients. Best-corrected visual acuity improved postoperatively compared with preoperatively in all three patients with macula-off retinal detachment (100%) and was equal to or better than the initial best-corrected visual acuity in 6 (60%) of the 10 patients with macula-on retinal detachment. Complications included increased intraocular pressure, cataract, and cystoid macular edema.Perfluorocarbon heavy liquid is a safe and effective material for short-term vitreoretinal tamponade following vitrectomy for giant retinal tear.

Purpose: This study aims to evaluate and correlate the levels of interleukin-6 (IL-6) and thrombin–antithrombin III complex (TAT) in the vitreous of patients with different vitreoretinal pathologies. Methods: Vitreous samples were collected from 78 patients scheduled for pars plana vitrectomy at a tertiary medical center. Patients were divided by the underlying vitreoretinal pathophysiology, as follows: macular hole (MH)/epiretinal membrane (ERM) (n = 26); rhegmatogenous retinal detachment (RRD) (n = 32); and proliferative diabetic retinopathy (PDR) (n = 20). Levels of IL-6 and TAT were measured by enzyme-linked immunosorbent assay and compared among the groups. Results: A significant difference was found in the vitreal IL-6 and TAT levels between the MH/ERM group and both the PDR and RRD groups (P < 0.001 for all). Diabetes was associated with higher IL-6 levels in the RRD group. Different relationships between the IL-6 and TAT levels were revealed in patients with different ocular pathologies. Conclusion: Our results imply that variations in vitreal TAT level may be attributable not only to an inflammatory reaction or blood–retinal barrier breakdown, but also to intraocular tissue-dependent regulation of thrombin.

Background: To elucidate the potential impact of diabetes mellitus on primary open-angle glaucoma pathology through vascular deficiency. Design: Cross-section analysis from a longitudinal, prospective study. Participants: Eighty-four open-angle glaucoma patients (20 diabetic open-angle glaucoma patients and 64 non-diabetic open-angle glaucoma patients) Methods: Patients were analyzed for ocular structure, ocular perfusion pressure (OPP), retrobulbar blood flow and retinal capillary perfusion. Statistical analysis was performed by SPSS version 18.0. Comparisons between groups were made as well as multivariate linear regression analysis. Main Outcome Measure: Retrobulbar blood flow and the retinal microcirculation. Results: Central retinal artery peak systolic velocity was 13.5% lower in diabetic patients (P = 0.007). In diabetic open-angle glaucoma patients, ocular perfusion pressure positively correlated with central retinal artery and temporal posterior ciliary artery peak systolic velocity (R = 0.476, P = 0.039 and R = 0.529, P = 0.02, respectively), and with central retinal artery and nasal posterior ciliary artery resistance index (R = 0.537, P = 0.018 and R = 0.566, P = 0.012 respectively). Average retinal nerve fibre layer positively correlated with central retinal artery peak systolic velocity and temporal posterior ciliary artery end diastolic velocity (R = 0.501, P = 0.029 and R = 0.553, P = 0.019, respectively), and negatively correlated with superior and inferior retinal avascular space in the diabetic group (R = −0.498, P = 0.030 and R = −0.700, P = 0.001, respectively); no correlations were found in the non-diabetic group. Negative correlations between retrobulbar and retinal circulations were only found in the diabetic open-angle glaucoma patients, whereas positive correlations between retinal flow and non-flow were only found in non-diabetic open-angle glaucoma patients. Conclusion: Diabetes may interfere with normal vascular regulation and contribute to glaucoma progression.

Purpose Determine the repeatability of color Doppler imaging (CDI) measurements in patients with open-angle glaucoma (OAG). Patients and methods We performed a cross-sectional, observational study of OAG patients participating in the Indianapolis Glaucoma Progression Study. Retrobulbar blood flow velocities and Pourcelot's vascular resistance index (RI) measured with CDI were examined. Two baseline measurements were obtained 1 to 2 weeks apart at the same time of day for all participants. Peak systolic and end diastolic blood flow velocities (PSV/EDV) were measured in the ophthalmic (OA), central retinal (CRA), and nasal and temporal short posterior ciliary arteries (N/TPCA) and RI was calculated. Intraclass correlation coefficient (ICC) between the 2 baselines was calculated. Results One hundred and sixteen patients with OAG [mean age 65.9 y (SD 10.9 y), 60% female] were examined in both baseline visits. In the OA, the intraobserver ICC for the PSV, EDV, and RI were all above 0.82. In the CRA, the intraobserver ICC for the PSV and RI were both above 0.8, whereas the EDV was 0.64. The intraobserver ICC in the N/TPCA for the PSV, EDV, and RI ranged from 0.71 to 0.88. The interobserver ICC was similar to the intraobserver ICC for the OA and the CRA but was lower than 0.7 in the EDV and RI of the T/NPCA. Conclusions Blood flow velocities and calculated vascular resistance of the OA, CRA, and PCAs conducted within 2 weeks in patients with OAG are repeatable. Intraobserver CDI measurements were found more reproducible than interobserver CDI analysis.

Background: The study compares the change in best-corrected visual acuity with the change in central retinal sensitivity before treatment and 6 months after treatment with photodynamic therapy in patients with symptomatic central serous chorio retinopathy. Design: Prospective, single-centre, interventional case series. Participants: Eleven consecutive patients with previously untreated central serous chorio retinopathy. Methods: Patients had microperimetry and best-corrected visual acuity recorded before and 6 months after treatment with photodynamic therapy. Refracted best-corrected visual acuity was assessed at 2 m and adjusted to give the number of letters read at 1 m. Threshold microperimetry was performed by presenting a Goldman III stimulus to 29 points over the central 12° around fixation. Significant visual improvement at 6 months was defined as a best-corrected visual acuity ≥10 letters or, microperimetry change in mean retinal sensitivity ≥2 decibels (dB). Main Outcome Measures: Improvement in best-corrected visual acuity compared with microperimetry following photodynamic therapy treatment in patients with central serous chorio retinopathy. Results: All patients reported a subjective improvement in vision and had complete resolution of subretinal fluid at 6 months. Two patients had a significant improvement in best-corrected visual acuity (mean ± SD +4.2 ± 5.8 letters), compared with all 11 patients who recorded a significant improvement in mean retinal sensitivity (mean ± SD 4.6 ± 1.9 dB) (P

Purpose: To report the outcome of retinal detachment surgery following trauma treated with small-gauge vitrectomy. Design: Retrospective chart review. Participants: Adult patients presenting with a retinal detachment following severe trauma between 2007 and 2009 that underwent vitreoretinal surgery with either 25- or 23-gauge vitrectomy. Methods: Data collected included; age, sex, eye, time interval between injury and diagnosis of retinal detachment, anatomical and functional success, complications, and length of follow up. Main Outcome Measures: Anatomical and functional outcome. Results: Nineteen consecutive adult patients with traumatic retinal detachment were included. The mean age was 51.4 ± 19.3 years; 68.5% were male. Thirteen patients (68.4%) presented with visual acuity of hand movement or worse including six patients with light perception only. Five eyes achieved 6/60 vision or better, and three eyes had visual acuity of 6/12 or better. During the period of follow up six eyes experienced a recurrent retinal detachment. Conclusion: Traumatic retinal detachment can be successful managed with small-gauge vitrectomy.

PURPOSE To compare intraocular pressure (IOP) measured by Goldmann applanation tonometry (GAT) and dynamic contour tonometry (DCT) and assess their relationship to central corneal thickness (CCT) in patients with primary open angle glaucoma (OAG). PATIENTS AND METHODS GAT, DCT, and CCT were assessed in 116 patients with OAG [mean age 65.9 (10.5); 59% female] participating in the Indianapolis Glaucoma Progression Study. GAT and DCT were measured in a randomized order followed by CCT (ultrasonic corneal pachymetry) during a single study visit. Bland-Altman plots were used to evaluate the limits of agreement between tonometery methodologies whereas multivariate regression analysis was used to evaluate the influence of CCT on GAT and DCT IOP measurements. RESULTS IOP values obtained by DCT and GAT showed a strong positive correlation in patients with OAG (r=0.93; P

Our purpose was to determine the anatomical outcome following small gauge vitrectomy for acute rhegmatogenous retinal detachment (RRD) operated by vitreoretinal fellows. We undertook a retrospective review of adult patients presenting with an acute RRD treated with small gauge vitrectomy where the operating surgeon was either a vitreoretinal fellow or consultant surgeon. The patient’s demographics were recorded as well as relevant clinical findings. The end point was determined to be the anatomical outcome and number of surgeries. Two hundred and twelve eyes were included in this study. The age range was 21–90 years, with approximately one third of the patients being female. The macula was attached in 53% at presentation, and 65% of the eyes were phakic. Primary re-attachment with a single operation was achieved in 75% of cases, and final re-attachment rate was 92%. Mean presenting visual acuity was LogMAR 1.07 (SD 1.09) and final visual acuity was LogMAR 0.63 (SD 0.85). We found no association between final anatomical success and experience of the surgeon (p = 0.6). We found that acute RRD treated by vitreoretinal fellows using small gauge vitrectomy did not place the patient at any discernable disadvantage.

Diabetic macular oedema (DMO) is an important cause of vision loss in patients with diabetes mellitus. The underlying mechanisms of DMO, on both macrocellular and microcellular levels, are discussed in this review. The pathophysiology of DMO can be described as a process whereby hyperglycaemia leads to overlapping and inter-related pathways that play a role not only in the initial vascular events, but also in the continued tissue insult that leads to chronic DMO. On a macrocellular level, DMO is believed to be in part caused by alterations in hydrostatic pressure, oxygen tension, oncotic pressure and shear stress. Three key components of the microvascular pathways include angiogenic factor expression, inflammation and oxidative stress. These molecular mediators, acting in conjunction with macrocellular factors, which are all stimulated in part by the hyperglycaemia and hypoxia, can have a direct endothelial effect leading to hyperpermeability, disruption of vascular endothelial cell junctions, and leukostasis. The interactions, signalling events and feedback loops between the various molecules are complicated and are not completely understood. However, by attempting to understand the pathways involved in DMO, we can help guide new treatment options targeted towards specific factors or mediators.

Glaucoma is a disease characterized by progressive optic neuropathy resulting in retinal ganglion cell death, which affects approximately 68 million people worldwide. Risk factors include intraocular pressure (IOP), genetics, race, age, and vascular factors. Exercise is known to affect IOP and systemic cardiovascular factors and, therefore, may affect glaucoma pathophysiology. This review discusses the results of articles relevant to glaucoma, IOP, ocular blood flow (OBF), and exercise. Isometric and dynamic exercises have been studied with respect to effects on IOP and OBF. Isometric exercise results in an acute decrease in IOP, which correlates with hypocapnia. Dynamic exercise results in a more pronounced but also short duration decrease in IOP. Physical fitness is associated with lower baseline IOP but diminished acute IOP-lowering response to exercise. Upon cessation of exercise, values return to pretrained levels within 1 month. In glaucoma patients, these IOP-lowering effects are greater than in healthy subjects. In healthy subjects, OBF is unchanged during exercise due to vascular autoregulation. This autoregulation fails at ocular perfusion pressures greater than 70% above baseline. In conclusion exercise in glaucoma patients results in acutely lowered IOP and lower baseline IOP. The effects of exercise on the prevention of glaucoma and glaucomatous progression remain unknown. The role of exercise in glaucoma management should be investigated.

To study the effect of intravitreal bevacizumab for the treatment of long-standing exudative age-related macular degeneration (AMD) and low visual acuity.Forty-seven patients (48 eyes) aged 57 to 90 years with AMD for 5 months or more and visual acuity of 20/150 or less were treated with one or more injections of bevacizumab 1.25 mg/0.05 mL between December 2005 and March 2007. The files were reviewed for background data, visual acuity, fluorescein angiography, retinal thickness, and complications.Thirty-two eyes were treated previously with photodynamic therapy. Mean duration of symptoms was 17.9 +/- 17.5 months; mean number of bevacizumab injections was 3.41 +/- 2; and mean follow-up was 27 +/- 15 weeks. Snellen visual acuity improved from 20/150 to hand movements (mean logMAR 1.34 +/- 0.29) to 20/50 to counting fingers (mean logMar 1.2 +/- 0.42) (P = 0.003, paired t-test). Visual acuity improved byor =3 lines in 12 eyes (25%); showed no change in 9 eyes (19%); and deteriorated byor =3 lines in 4 eyes (8.3%). Visual acuity was at least 20/150 in 16 eyes (33.3%) at the end of follow-up compared with 4 eyes (8.3%) before treatment (P = 0.02, McNemar test). Mean central retinal thickness (measured in 22 eyes) decreased from 324 +/- 121 mum to 264 +/- 65 mum (P = 0.02, paired t-test).Patients with chronic exudative AMD and low visual acuity may benefit from intravitreal bevacizumab injections.

Rita Ehrlich1, Alon Harris1, Nisha S Kheradiya1, Diana M Winston1, Thomas A Ciulla3, Barbara Wirostko21Indiana University School of Medicine, Department of Ophthalmology, Indianapolis, IN, USA; 2Stony Brook University Medical Center Research Way, Department of Ophthalmology, Stony Brook, NY, USA; 3Retina Service, Midwest Eye Institute, Attending Physician and Surgeon, Methodist Hospital, Indianapolis, IN, USAAbstract: Age-related macular degeneration (AMD) is an ocular disease that causes damage to the retinal macula, mostly in the elderly. Normal aging processes can lead to structural and blood flow changes that can predispose patients to AMD, although advanced age does not inevitably cause AMD. In this review, we describe changes that occur in the macular structure, such as the retinal pigment epithelium and Bruch’s membrane, with advancing age and in AMD. The role of genetics in AMD and age-related changes in ocular blood flow that may play a role in the pathogenesis of AMD are also discussed. Understanding the pathophysiology of AMD development can help guide future research to further comprehend this disease and to develop better treatments to prevent its irreversible central vision loss in the elderly.Keywords: age-related macular degeneration, aging, blood flow, eye, retina, macula, vision

Purpose To examine the anatomical and refractive outcomes of infrared diode laser photocoagulation (DLPC) for the treatment of threshold retinopathy of prematurity (ROP). Methods The charts of all consecutive premature neonates with ROP treated by DLPC at our tertiary center from December 1, 1996, to December 31, 2004, were reviewed. Results The group included 100 neonates (194 eyes) with a mean birth weight +/- SD of 833.9 +/- 250.3 g and a mean gestational age +/- SD of 26 +/- 1.9 weeks. Sixty-two percent of neonates had zone I or posterior zone II ROP. Each eye received a mean +/- SD of 1,740 +/- 990 laser applications, and 21% of eyes received an additional 1 to 2 rows posterior to the ridge. Neonates treated after December 2003 (cutoff date of the Early Treatment of Retinopathy of Prematurity study) underwent a significantly greater number of laser applications (mean +/- SD, 2,286 +/- 1,087) than did neonates treated earlier. Anatomical results of laser treatment were favorable for 179 eyes (92.3%) at a mean follow-up +/- SD of 33.6 +/- 27.2 months. After vitreoretinal surgery, partial or total retinal detachment was documented for 2.5% of patients who received posterior-to-the-ridge laser treatment and 3.8% of patients treated only on the avascular retina. Refractive data were available for 134 eyes: 55.2% had myopia of -5 diopters (31.3%) or greater (23.9%). Strabismus was found in 21 (28.8%) of 73 neonates tested. Gestational age was correlated with corrected age at treatment, zone of ROP, number of laser applications, and spherical equivalent. Snellen visual acuity of 6/12 or more occurred in 17 of 24 patients who complied with testing. Conclusion DLPC is a safe and effective treatment for ROP. Neonates of lower gestational age and birth weight require earlier and more aggressive laser treatment and may have a higher refractive error.

Objective To assess the comprehensive effects of raloxifene hydrochloride on retinal, choroidal and retrobulbar hemodynamics and on visual function in post-menopausal women. Design Twenty-four post-menopausal women (age 55 ± 3.8 years) were recruited for this cross-sectional study: 12 received placebo and 12 received raloxifene hydrochloride 60 mg once a day for 3 months. Baseline measurements of both groups included heart rate (HR), blood pressure (BP), visual acuity, contrast sensitivity and intraocular pressure (IOP) for both eyes. A comprehensive ocular blood flow (OBF) assessment was obtained for each patient in a randomly chosen study eye. Retinal blood flow data was obtained using confocal scanning laser Doppler flowmetry [Heidelberg Retinal Flowmeter (HRF)]. Color Doppler imaging (CDI) was used to assess retrobulbar hemodynamics in the ophthalmic, central retinal, short nasal and temporal posterior ciliary arteries. Baseline vision and hemodynamics in post-menopausal subjects were compared using paired Student’s t tests, and the percentage change in baseline versus 3-month parameters was analyzed. Results There were no statistically significant differences between 3 months of raloxifene therapy and placebo in terms of age, HR, arterial or mean BP, visual acuity, contrast sensitivity, IOP or retinal or retrobulbar blood flow. Conclusion Raloxifene therapy at 60 mg/day had no clinically significant impact on BP, IOP or OBF in post-menopausal women.

Pseudoexfoliation syndrome is the most common clinical precursor to secondary open-angle glaucoma worldwide.1 It is a systemic disease that is characterized by the progressive accumulation of whitish-grey fibrillar proteins in various organs, especially ocular tissues, such as the lens, pupil border, zonules, orbital tissues, and trabecular meshwork. It is a major risk factor for glaucoma development; therefore, early detection is important in order to monitor signs of disease progression and to initiate aggressive medical and/or surgical therapies. Pseudoexfoliation syndrome prevalence increases with age and is associated with elevated intraocular pressures. Many studies, such as the Thessaloniki Eye Study2 and Blue Mountain Eye Study,3 have found that pseudoexfoliation syndrome prevalence varies from 2.3 to 11.9% amongst different populations.4-13 Furthermore, 14.2 to 55.1% of patients with pseudoexfoliation syndrome are likely to progress into openangle glaucoma.2,14 The Early Manifest Glaucoma found that pseudoexfoliation is a strong predictor of glaucoma progression independent of elevated intraocular pressures and other risk factors.15 Additionally, pseudoexfoliation has also been shown to be an important independent risk factor for glaucoma development in patients with ocular hypertension.14 In 14 to 29% of cases, pseudoexfoliation syndrome progresses from a unilateral disease to bilateral disease.16,17 The pseudoexfoliative deposits are composed of complex glycoprotein/proteoglycan molecules, bearing similarities to epitopes within the basement membrane and the elastic fiber system.18 These microfibrillar subunits are surrounded by an amorphous matrix of elastic fibers (such as elastin, tropoelastin, amyloid P, and vitronectin) and elastic microfibrils (such as fibrillin-1, microfibril-associated glycoprotein-1, and latent tumor growth factor-binding proteins).18 The nature of pseudoexfoliative material and the stimulus for its production are unknown.19 Imbalances between matrix metalloproteinases and tissue inhibitors of matrix metalloproteinases and extensive cross-linking processes are involved in pseudoexfoliative fiber formation, whereby the pathologic material is not properly degraded but instead progressively accumulates within the tissues over time.20 Furthermore, the accumulation of these pseudoexfoliation deposits within the pericellular region can disrupt the underlying basement membrane and lead to a degenerative fibrillopathy21-23 and dysfunction of the vasculature. Over time, the blood vessels experience reduced contractility and elasticity, which can eventually lead to alterations in blood flow velocity (Fig. 1).

Amir Sternfeld, Ruth Axer-Siegel, Hadas Stiebel-Kalish, Dov Weinberger, Rita Ehrlich Department of Ophthalmology, Rabin Medical Center, Beilinson Campus, Petach Tikva, Israel Purpose: To evaluate the outcomes and complications of patients with diabetic tractional retinal detachment (TRD) treated with pars plana vitrectomy (PPV).Patients and methods: We retrospectively studied a case series of 24 eyes of 21 patients at a single tertiary, university-affiliated medical center. A review was carried out on patients who underwent PPV for the management of TRD due to proliferative diabetic retinopathy from October 2011 to November 2013. Preoperative and final visual outcomes, intraoperative and postoperative complications, and medical background were evaluated.Results: A 23G instrumentation was used in 23 eyes (95.8%), and a 25G instrumentation in one (4.2%). Mean postoperative follow-up time was 13.3months (4–30months). Visual acuity significantly improved from logarithm of the minimum angle of resolution (LogMAR) 1.48 to LogMAR 1.05 (P

Purpose: Subretinal hemorrhage is one of the most serious complications of exudative age-related macular degeneration (AMD). Treatment with vitreous surgery with or without plasminogen activator, fluid-gas exchange, or perfluorocarbon yields only a small improvement in visual acuity. Patients and Methods: The files of 24 patients with submacular hemorrhage secondary to AMD who were treated by injection of perfluoropropane gas (C3F8) (11 patients) or sulfur hexafluoride (SF6) (13 patients) were reviewed for visual acuity before and after the procedure and time of treatment from onset of symptoms. Results: For the whole sample, pneumatic displacement led to a statistically significant improvement in mean visual acuity (p = 0.015). A significant difference between pre- and postoperative visual acuity was found for the patients treated with SF6 (p = 0.034), but not for the patients treated with C3F8 (p = 0.245). Conclusion: The use of gas injection to displace submacular hemorrhage can significantly improve visual acuity.

BACKGROUND AND OBJECTIVE To report the outcome of combined verteporfin photodynamic therapy (PDT) and intravitreal triamcinolone acetonide (IVTA) for the treatment of choroidal neovascularization (CNV) with serous pigment epithelium detachment (PED) due to age-related macular degeneration (AMD). PATIENTS AND METHODS The files of all consecutive patients with CNV and serous PED who received PDT and IVTA either primarily (primary treatment group) or following previous unsuccessful PDT (secondary treatment group) were reviewed for visual and angiographic results. RESULTS Ten patients (11 eyes) were included. Mean number of PDT sessions was 3.18; 8 eyes received one IVTA injection and 3 eyes received two IVTA injections. Thirty-six percent of patients retained their initial visual acuity after a mean follow-up of 15.3 months. Loss of 3 or more Snellen lines was noted in 2 of 3 eyes in the primary treatment group and 5 of 8 eyes in the secondary treatment group. Increased intraocular pressure developed in 3 patients and was controlled by topical medications. CONCLUSIONS Although combined PDT and IVTA may be considered for CNV with serous PED in patients with poor prognosis with PDT alone, the regimen as administered in this small series was not beneficial. Further studies are required to determine whether alternate sequences, timing, or doses would yield a better outcome. [Ophthalmic Surg Lasers Imaging 2006;37:455-461.] AUTHORS From the Department of Ophthalmology (RA-S, RE, IA, MK, IR, DW), Rabin Medical Center, Beilinson Campus, Petah Tiqva; the Mor Institute for Medical Data (RA-S, MK, EP, DW), Bnei Berak; and the Sackler Faculty of Medicine (RA-S, DW), Tel Aviv University, Tel Aviv, Israel. Accepted for publication February 8, 2006. Address reprint requests to Ruth Axer-Siegel, MD, Department of Ophthalmology, Rabin Medical Center, Beilinson Campus, Petah Tiqva 49100, Israel.

Atrial septal defect (ASD) is a common diagnosis in young adults with congenital heart disease. The aim of this study was to determine if ocular symptoms following percutaneous treatment are due to microemboli. The study group included 20 adult patients (9 men, 11 women, mean age 57.2 years) with ASD who had undergone successful closure with the Amplatzer occluder. The patients were treated with aspirin or warfarin during 6 months after the procedure. All were evaluated neurologically and an ocular medical history was obtained. Ocular examination included the 120-point Humphrey visual field. Transcranial Doppler (TCD) was performed to monitor the middle cerebral artery. Two patients complained of amaurosis fugax at 1 and 3 months after the procedure, and two patients complained of blurred vision at 3 and 4 months after the procedure. TCD performed for 45 minutes within 24 hours of the visual complaints revealed no abnormalities. In all patients, the neurological and ocular examinations, including the visual field test, were normal. In conclusion, microembolic events could not be demonstrated to be the cause of the ocular complaints in patients with ASD treated with Amplatzer occluder. Further studies in larger samples are needed to confirm these results.