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Abstract Purpose Comparing between the visual outcomes and post operative complications of two surgical treatments for sub macular hemorrhage, pars plana vitrectomy with tissue plasminogen activator (tPA) injection procedure, and pneumatic displacement of submacular hemorrhage with intravitreal tPA injection. Methods A retrospective chart review of patients with sub macular hemorrhage (SMH) was performed. Data was collected from 150 patients with sub macular hemorrhage. Patients were followed up from the day of admission and up to a year post surgery. Evaluation included visual acuity, optical coherence tomography (OCT), fundus examination and rates of complications. Results Pars plana vitrectomy procedure has showed a better visual outcome in small SMH. Comparing complications between the two treatment modalities, no significant difference has been found in the study. Conclusions Pars plana vitrectomy and tPA showed a clear advantage with a trend of better visual acuity as well as a significant predictor to better visual acuity for small and medium sub macular hemorrhage.

Purpose: Comparing between the visual outcomes and post operative complications of two surgical treatments for sub macular hemorrhage, pars plana vitrectomy with tissue plasminogen activator (tPA) injection procedure, and pneumatic displacement of submacular hemorrhage with intravitreal tPA injection. Methods: A retrospective chart review of patients with sub macular hemorrhage (SMH) was performed. Data was collected from 150 patients with sub macular hemorrhage. Patients were followed up from the day of admission and up to a year post surgery. Evaluation included visual acuity, optical coherence tomography (OCT), fundus examination and rates of complications. Results: Pars plana vitrectomy procedure has showed a better visual outcome in small SMH. Comparing complications between the two treatment modalities, no significant difference has been found in the study. Conclusions: Pars plana vitrectomy and tPA showed a clear advantage with a trend of better visual acuity as well as a significant predictor to better visual acuity for small and medium sub macular hemorrhage. Why carry out this study?: • Either Pneumatic Displacement and tPA injection, or Pars Plana Vitrectomy with subretinal tPA injection were shown to be effective in hemo displacement. • There is no consensus among the therapists regarding preferred treatment options for subretinal bleeding. What was learned from the study?: • PPV + tPA exhibited a clear advantage with a trend of better BCVA at all time points as well as a significant predictor to better BCVA for small and medium SMH. • Comparing complications between the two treatment modalities, we did not find a significant difference. Implying to equal safety to both surgeries. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To evaluate the therapeutic effects of intra-vitreal injection Bevacizumab combined with Diclofenac-Na versus intra-vitreal Bevacizumab alone in the treatment of naïve diabetic macular edema. METHODS: In this prospective, randomized interventional clinical trial, 40 eyes of 40 participants were enrolled for trial conducted at an Ophthalmology department of Qazi Hussain Medical Complex, Nowshera. Twenty eyes each included in the intra-vitreal Bevacizumab and bevacizumab plus diclofenac group via random sampling technique. The main outcome variable was a change in best-corrected visual acuity (BC-VA) in log MAR at 4th, 12th and 24th week. The secondary outcomes included mean change in central subfield thickness (CSFT) of macula and possible injection-related side effects. RESULTS: Marked improvement in BC-VA was observed in both therapeutic groups (mean change in Log MAR: 0.324±0.411 and 0.562±0.388 for bevacizumab alone and combination group, respectively). The difference in BC-VA change was in favor of combination group; however, the level didn’t achieve statistical significance (p = 0.08). Significant decrease in CSFT was noted in both groups (mean reductions: 178.02 ± 166.42, 214.55 ± 132.65) for bevacizumab and combination, respectively). Comparison of CSFT changes between groups revealed that combination decreased CSFT more than bevacizumab, but the difference was statistically insignificant (p = 0.07). Neither injection related side effects nor any marked change in intraocular pressure was observed in either groups. CONCLUSION: In diabetic macular edema, superiority of combination therapy over Bevacizumab alone was evident, esp. with regard to structural improvement in macula.

To investigate music selection as a treatment for anxiety during Intravitreal injections (IVI) for individuals of varying cultures. 106 individuals were enrolled in this randomized controlled study. Individuals were randomized into one to three categories: (1) a control group in which the IVI procedure was performed without music (n = 35), (2) an experimental group in which the music was selected by the physician (n = 36), (3) an experimental group in which the music was selected by the patient (n = 35). After the procedure, all patients responded to a questionnaire regarding their level of experienced anxiety, pain and discomfort (grade 0–10). The primary outcome was anxiety level during the procedure. The experimental group in which patients selected music had higher number of patients with low anxiety score compared to the other groups (anxiety score <4 in 19,18 and 27 patients, respectively, p =.04). Interestingly, patients who answered the questionnaire in Arabic were less likely to desire music on subsequent injections compared to Hebrew and English speakers (52% Vs 78% Vs 100%, p =.02). Music was deemed by both experimental groups as an effective method to induce relaxation (average score of 6.6 and 7.2 in group 2 and 3, respectively). Preference for music on subsequent injections was increased in both experimental groups compared to the control group (P <.01). Patients in the third group preferred music selection on future injections more than the other groups (P <.01). Music selection may be an effective way to reduce anxiety levels during IVI. Preference for music during future injections is higher in patients who were exposed to music during IVI and may be influenced by culture. [ABSTRACT FROM AUTHOR]

We experienced an atypical endophthalmitis occurring post consecutively performed in-office procedures; an intravitreal injection (IVI) of ranibizumab followed by an anterior chamber (AC) paracentesis performed twice in an eye with neovascular glaucoma (NVG). A 52-year-old diabetic male who was asymptomatic developed signs of endophthalmitis and decreased vision without pain in his left eye a few days post-IVI and AC paracentesis. The condition worsened after an initial vitreous tap and injection of antibiotics. Cultures of vitreous and aqueous samples were negative. Complete resolution occurred after a pars plana vitrectomy with IVI of antibiotics and steroid with removal of a dense “yellowish-brown” fibrinous plaque. The absence of pain, presence of a peculiar colored fibrin, mild-to-moderate vitritis without retinitis, negative cultures, and complete recovery despite the fulminant presentation; favor a diagnosis of inflammation over infection. We hypothesize that a micro-leak from a 26-gauge AC tap tract might have served as an entry port for 5% povidone-iodine from the ocular surface thus inciting inflammation. However, an exuberant inflammatory response that can be typically seen in NVG eyes after intraocular procedures cannot be excluded. Various causes of inflammation post-procedures, both toxic and nontoxic should be considered in atypical culture-negative fulminant endophthalmitis cases with good outcome posttreatment. Any minor ocular procedure may carry a risk of such complication. Patient counseling and care must be exercised in performing these procedures.

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We experienced an atypical endophthalmitis occurring post consecutively performed in-office procedures; an intravitreal injection (IVI) of ranibizumab followed by an anterior chamber (AC) paracentesis performed twice in an eye with neovascular glaucoma (NVG). A 52-year-old diabetic male who was asymptomatic developed signs of endophthalmitis and decreased vision without pain in his left eye a few days post-IVI and AC paracentesis. The condition worsened after an initial vitreous tap and injection of antibiotics. Cultures of vitreous and aqueous samples were negative. Complete resolution occurred after a pars plana vitrectomy with IVI of antibiotics and steroid with removal of a dense "yellowish-brown" fibrinous plaque. The absence of pain, presence of a peculiar colored fibrin, mild-to-moderate vitritis without retinitis, negative cultures, and complete recovery despite the fulminant presentation; favor a diagnosis of inflammation over infection. We hypothesize that a micro-leak from a 26-gauge AC tap tract might have served as an entry port for 5% povidone-iodine from the ocular surface thus inciting inflammation. However, an exuberant inflammatory response that can be typically seen in NVG eyes after intraocular procedures cannot be excluded. Various causes of inflammation post-procedures, both toxic and nontoxic should be considered in atypical culture-negative fulminant endophthalmitis cases with good outcome posttreatment. Any minor ocular procedure may carry a risk of such complication. Patient counseling and care must be exercised in performing these procedures. [ABSTRACT FROM AUTHOR]

Drug delivery to vitreous in comparison with drug delivery to the other parts of the eye is complicated and challenging due to the existence of various anatomical and physiological barriers. Developing injectable intra-vitreal implant could be beneficial in this regard. Herein, poly(hydroxybutyrate-co-valerate) (PHBV) implants were fabricated and optimized using response surface method for budesonide (BZ) delivery. The acquired implants were characterized in regard to the stability of the ingredients during fabrication process, drug loading amount, and drug release pattern (in PBS-HA-A and in vitreous medium). According to this research and statistical analysis performed, first HV% (hydroxyvalerate) then molecular weight and ratio of PEG as pore former affect respectively release rate and burst strength of BZ with different coefficients. Drug release profile in rabbit eye correlated well with that of in vitro (R2 = 0.9861, p ˂ 0.0001). No significant changes were seen in ERG waves, intraocular pressure, and histological studies during the in vivo part of the project. Using 8% HV, 20% PEG/PHBV, and higher molecular weight PEG (i.e., 6000), the optimum formulation was achieved. Toxicity and biocompatibility of the optimized formulation, which were evaluated in vivo, indicated the suitability of design implant for intra-vitreal BZ delivery. [ABSTRACT FROM AUTHOR]

Uveitis is a major cause of vision loss. Methotrexate (MTX) has been widely used in uveitis due to its relatively safe profile. The purpose of this study was to evaluate the effects of two different dosages of MTX via intra-vitreal administration for treatment of endotoxin induced uveitis (EIU) in an experimental model. Thirty-five healthy rabbits were randomly divided into four groups and all animals were tolerated intra-vitreal injections. The first group received normal saline (NS), the second group received normal saline plus Salmonella typhimurium lipopolysaccharide endotoxin (LPS), (NS+LPS), the third group received 400 μg MTX plus LPS (LPS+MTX 400) and the fourth group received 800 μg MTX plus LPS (LPS+MTX 800). Intraocular inflammation was evaluated by clinical examination scoring during 7 post-injection days and histopathological examination at the end of study. Kruskal-Wallis and Mann-Whitney U tests were used to compare the histopathological and clinical scores. According to the clinical examinations, all groups demonstrated higher uveitis score than group 1 on first post-injection day. Also, groups 2 and 3 showed greater uveitis score than group 4. On the third, fifth and seventh post-injection days, clinical uveitis score in groups 2, 3 and 4 was significantly higher than group 1. The mean histopathological inflammation intensity scores in groups 2, 3 and 4 were significantly higher than group 1. Single intra-vitreal injection of 400 μg and 800 μg of MTX did not show significant anti-inflammatory effects on EIU in rabbits. [ABSTRACT FROM AUTHOR]

Uveitis is a major cause of vision loss. Methotrexate (MTX) has been widely used in uveitis due to its relatively safe profile. The purpose of this study was to evaluate the effects of two different dosages of MTX via intra-vitreal administration for treatment of endotoxin induced uveitis (EIU) in an experimental model. Thirty-five healthy rabbits were randomly divided into four groups and all animals were tolerated intra-vitreal injections. The first group received normal saline (NS), the second group received normal saline plus Salmonella typhimurium lipopolysaccharide endotoxin (LPS), (NS+LPS), the third group received 400 μg MTX plus LPS (LPS+MTX 400) and the fourth group received 800 μg MTX plus LPS (LPS+MTX 800). Intraocular inflammation was evaluated by clinical examination scoring during 7 post-injection days and histopathological examination at the end of study. Kruskal-Wallis and Mann-Whitney U tests were used to compare the histopathological and clinical scores. According to the clinical examinations, all groups demonstrated higher uveitis score than group 1 on first post-injection day. Also, groups 2 and 3 showed greater uveitis score than group 4. On the third, fifth and seventh post-injection days, clinical uveitis score in groups 2, 3 and 4 was significantly higher than group 1. The mean histopathological inflammation intensity scores in groups 2, 3 and 4 were significantly higher than group 1. Single intra-vitreal injection of 400 μg and 800 μg of MTX did not show significant anti-inflammatory effects on EIU in rabbits. [ABSTRACT FROM AUTHOR]

Amyloid-beta (Aβ) is a group of aggregation-prone, 38- to 43-amino acid peptides generated in the eye and other organs. Numerous studies suggest that the excessive build-up of low-molecular-weight soluble oligomers of Aß plays a role in the progression of Alzheimer's disease and other brain degenerative diseases. Recent studies raise the hypothesis that excessive Aß levels may contribute also to certain retinal degenerative diseases. These findings, together with evidence that a major portion of Aß is released as monomer into the extracellular space, raise the possibility that a technology enabling the enzymatic break-down of monomeric Aß in the living eye under physiological conditions could prove useful for research on ocular Aß physiology and, perhaps ultimately, for therapeutic applications. Neprilysin (NEP), an endopeptidase known to cleave Aß monomer into inactive products, is a membrane-associated protein. However, sNEP, a recombinant form of the NEP catalytic domain, is soluble in aqueous medium. With the aim of determining the Aß-cleaving activity of exogenous sNEP in the microenvironment of the intact eye, we analyzed the effect of intra-vitreally delivered sNEP on ocular Aß levels in mice that exhibit readily measurable, aqueous buffer-extractable Aß40 and Aß42, two principal forms of Aß. Anesthetized 10-month wild-type (C57BL/6J) and 2-3-month 5XFAD transgenic mice received intra-vitreal injections of sNEP (0.004-10 µg) in one eye and were sacrificed at defined post-treatment times (30 min - 12 weeks). Eye tissues (combined lens, vitreous, retina, RPE and choroid) were homogenized in phosphate-buffered saline, and analyzed for Aß40 and Aß42 (ELISA) and for total protein (Bradford assay). The fellow, untreated eye of each mouse served as control, and concentrations of Aß (pmol/g protein) in the treated eye were normalized to that of the untreated control eye. In C57BL/6J mice, as measured at 2 h after sNEP treatment, increasing amounts of injected sNEP yielded progressively greater reductions of Aß40, ranging from 12% ± 3% (mean ± SEM; n = 3) with 4 ng sNEP to 85% ± 13% (n = 5) with 10 µg sNEP. At 4 ng sNEP the average Aß40 reduction reached >70% by 24 h following treatment and remained near this level for about 8 weeks. In 5XFAD mice, 10 µg sNEP produced an Aß40 decrease of 99% ± 1% (n = 4) and a substantial although smaller decrease in Aß42 (42% ± 36%; n = 4) within 24 h. Electroretinograms (ERGs) were recorded from eyes of C57BL/6J and 5XFAD mice at 9 days following treatment with 4 ng or 10 µg sNEP, conditions that on average led, respectively, to an 82% and 91% Aß40 reduction in C57BL/6J eyes, an 87% and 92% Aß40 reduction in 5XFAD eyes, and a 23% and 52% Aß42 reduction in 5XFAD eyes. In all cases, sNEP-treated eyes exhibited robust ERG responses, consistent with a general tolerance of the posterior eye tissues to the investigated conditions of sNEP treatment. The sNEP-mediated decrease of ocular Aß levels reported here represents a possible approach for determining effects of Aß reduction in normally functioning eyes and in models of retinal degenerative disease. [ABSTRACT FROM AUTHOR]

Current therapy to slow disease progression in patients with neovascular age-related macular degeneration (AMD) often entails intra-vitreal injection of an anti-vascular endothelial growth factor (VEGF) agent, that begins with a three-month loading phase of four weekly injections followed by regular monthly visits with clinician-determined re-treatment. The effects of AMD on quality of life and visual function have been extensively reported in the literature, however, less is known about the burden imposed on patients by the arduous and often indefinite treatment schedule which habitually follows a diagnosis of wet AMD. To date, no systematic review has been conducted of research investigating patients’ experiences of anti-VEGF treatment for AMD. A systematic search of the Embase, Medline, PsycINFO and PubMed electronic databases was undertaken to identify all studies between January 2004 and December 2013, published in the English language and involving human participants. A hand-search of an additional four journals was conducted. Ten articles were identified for inclusion in this review. A critical appraisal was undertaken using the Critical Appraisal Skills Programme Qualitative Research Checklist and the results synthesised to form a narrative review. Few studies to date have investigated patients’ experiences of treatment for AMD. These studies have focused primarily on patients’ experiences of the injection procedure with respect to pain and anxiety. Anticipated discomfort is often greater than actual discomfort experienced during intra-vitreal injection. However, different stages of the treatment procedure produce varying levels of patient discomfort. No one method of anaesthesia has consistently been shown to be more effective in reducing discomfort associated with treatment. Common reasons underlying patient apprehension surrounding treatment include the thought of having an injection, fear of losing eyesight and fear of the unknown. Whilst these studies have not been without their methodological limitations, they provide a platform for further exploration of the patient experience. [ABSTRACT FROM PUBLISHER]

Aim: To evaluate the dead spaces resulting from different designs of the insulin injectors used for intravitreal injections and the amounts of drug doses., Methods: In the study, five different brands of sterile insulin injectors of 1 mL were used for the test. The weight of the injectors was determined before and after filling the injectors with 0.05 and 0.1 mL distilled water. The weight of the injectors was measured with and without the needle after the water within the injectors had been taken out and weight differences were measured. The difference between the intended amount of fluid to be thrown out and the weight of the fluid remaining in the injector was calculated as percent error., Results: After throwing out 0.05 mL distilled water from the injector, weights of the Beybi ® , Traf ® , Becton Dickinson ® , Ayset ® , and Setojet ® brands of injectors with 30 G needle were detected to increase the mean 0.0220 ± 0.006 g, 0.0208 ± 0.008 g, 0.0355 ± 0.016 g, 0.0219 ± 0.017 g, and 0.0150 ± 0.007 g, respectively compared to the weights of the dry injectors. The 0.1 mL injector group was found to be mean 0.0350 ± 0.014 g, 0.0264 ± 0.008 g, 0.0405 ± 0.015 g, 0.0272 ± 0.013 g, and 0.0245 ± 0.014 g, respectively. The maximum increase due to the dead spaces in the injectors was found in the Becton Dickinson ® injector, both in the 0.05 mL and the 0.1 mL groups ( p  < 0.000)., Conclusion: The injector designs may affect the dose of IVI required to be given. More correct amounts of drugs may be administered via the intra-vitreal route through designs that reduce the dead spaces at the end part of the injector and between the inner wall and the plunger.

Uveitis is a major cause of vision loss. Methotrexate (MTX) has been widely used in uveitis due to its relatively safe profile. The purpose of this study was to evaluate the effects of two different dosages of MTX via intra-vitreal administration for treatment of endotoxin induced uveitis (EIU) in an experimental model. Thirty-five healthy rabbits were randomly divided into four groups and all animals were tolerated intra-vitreal injections. The first group received normal saline (NS), the second group received normal saline plus Salmonella typhimurium lipopolysaccharide endotoxin (LPS), (NS+LPS), the third group received 400 μg MTX plus LPS (LPS+MTX 400) and the fourth group received 800 μg MTX plus LPS (LPS+MTX 800). Intra-ocular inflammation was evaluated by clinical examination scoring during 7 post-injection days and histopathological examination at the end of study. Kruskal-Wallis and Mann-Whitney U tests were used to compare the histopathological and clinical scores. According to the clinical examinations, all groups demonstrated higher uveitis score than group 1 on first post-injection day. Also, groups 2 and 3 showed greater uveitis score than group 4. On the third, fifth and seventh post-injection days, clinical uveitis score in groups 2, 3 and 4 was significantly higher than group 1. The mean histopathological inflammation intensity scores in groups 2, 3 and 4 were significantly higher than group 1. Single intra-vitreal injection of 400 μg and 800 μg of MTX did not show significant anti-inflammatory effects on EIU in rabbits., Competing Interests: The authors declare no conflict of interest.