Displaying publications 1 - 20 of 39 in total

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  1. Gowda A, Bahrami B, Jie WWJ, Casson R, Chan WO
    Surv Ophthalmol, 2024;69(2):173-178.
    PMID: 37806565 DOI: 10.1016/j.survophthal.2023.10.004
    Anti-vascular endothelial growth factor (anti-VEGF) injections have revolutionized the field of ophthalmology, and their use in a variety of retinal diseases is growing. One target disease is peripheral exudative hemorrhagic chorioretinopathy, a disease that is uncommon and poorly understood. Despite this, there are numerous studies and case reports outlining the potential role of intravitreal injection of anti-VEGF medicines to treat it. As such, an evidence-based understanding of its risk-benefit profile is vital. We performed a comprehensive search in the PubMed, Google Scholar, and Cochrane databases for published studies and case reports relating to the use of anti-VEGF injections in peripheral exudative hemorrhagic chorioretinopathy. Anti-VEGF was first used in 2010 to aid in the management of peripheral exudative hemorrhagic chorioretinopathy. Since then, it has been increasingly used to manage this disease. Other potential management strategies, including laser photocoagulation, cryotherapy, photodynamic therapy, and vitrectomy are explored and compared with anti-VEGF where possible. Anti-VEGF appears to be an effective therapy in managing peripheral exudative hemorrhagic chorioretinopathy, especially when there is an exudative threat to the macula.
    Matched MeSH terms: Intravitreal Injections
  2. Nursyafiqah MT, Siti-Azrin AH, Yaacob NM, Wan-Nor-Asyikeen WA, Zunaina E
    Trop Med Int Health, 2023 Apr;28(4):300-307.
    PMID: 36787961 DOI: 10.1111/tmi.13862
    OBJECTIVE: Intravitreal ranibizumab is one of the anti-vascular endothelial growth factors used for the treatment of diabetic macular oedema, not always successfully. We aimed to identify the factors affecting the changes of central macular thickness after induction treatment with intravitreal ranibizumab, to predict the treatment effect and facilitate early treatment decisions.

    METHODS: Cross-sectional study involving a retrospective record review of diabetic macular oedema patients who received an induction treatment of three monthly 0.5 mg intravitreal ranibizumab injections between 2016 and 2019. Central macular thickness was measured at baseline and 3 months post-treatment. Linear regression was applied to identify the factors associated with the changes of central macular thickness.

    RESULTS: A total of 153 diabetic macular oedema patients were involved in this study. Their mean age was 57.5 ± 7.7 years, 54.9% were female. The mean change of central macular thickness from baseline to 3 months after completed induction treatment of intravitreal ranibizumab was 155.5 ± 137.8 μm. Factors significantly associated with changes of central macular thickness were baseline central macular thickness [b = 0.73; 95% (CI): 0.63, 0.84; p = <0.001] and presence of subretinal fluid [b = 35.43; 95% CI: 3.70, 67.16; p = 0.029].

    CONCLUSION: Thicker baseline central macular thickness and presence of subretinal fluid were the factors significantly associated with greater changes of central macular thickness in diabetic macular oedema patients after receiving three injections of intravitreal ranibizumab.

    Matched MeSH terms: Intravitreal Injections
  3. Mishra D, Gade S, Glover K, Sheshala R, Singh TRR
    Curr Eye Res, 2023 Feb;48(2):208-218.
    PMID: 36036478 DOI: 10.1080/02713683.2022.2119254
    Purpose: Intravitreal administration of drug molecules is one of the most common routes for treating posterior segment eye diseases. However, the properties of vitreous humour changes with the time. A number of ocular complications such as liquefaction of the vitreous humour, solidification of the vitreous humour in the central vitreous cavity and detachment of the limiting membrane due to the shrinking of vitreous humour are some of the factors that can drastically affect the efficacy of therapeutics delivered via intravitreal route. Although significant research has been conducted for studying the properties of vitreous humour and its changes during the ageing process, there have been limited work to understand the effect of these changes on therapeutic efficacy of intravitreal drug delivery systems. Therefore, in this review we discussed both the coomposition and characteristics of the vitreous humour, and their subsequent influence on intravitreal drug delivery.Methods: Articles were searched on Scopus, PubMed and Web of Science up to March 2022.Results: In this review, we discussed the biological composition and biomechanical properties of vitreous humour, methods to study the properties of vitreous humour and the changes in these properties and their relevance in ocular drug delivery field, with the aim to provide a useful insight into these aspects which can aid the process of development of novel intravitreal drug delivery systems.Conclusions: The composition and characteristics of the vitreous humour, and how these change during natural aging processes, directly influence intravitreal drug delivery. This review therefore highlights the importance of understanding the properties of the vitreous and identifies the need to achieve greater understanding of how changing properties of the vitreous affect the therapeutic efficacy of drugs administered for the treatment of posterior eye diseases.
    Matched MeSH terms: Intravitreal Injections
  4. Zaini MA, Mohd Zain A, Din NM, Mustapha M, Sidi H
    PLoS One, 2023;18(8):e0290260.
    PMID: 37624864 DOI: 10.1371/journal.pone.0290260
    BACKGROUND: Since the enforcement of the Movement Control Order (MCO) to contain the spread of COVID -19 infection in Malaysia, most clinic appointments have been rescheduled and procedures and surgeries postponed to a later date. Clinic appointments including intravitreal endothelial growth factor (anti-VEGF) treatment for patients with diabetic macular edema (DME) were also no exception to the postponement. This measure takes a psychological toll on patients because of the overwhelming concern for their eye condition. This study was conducted to assess the psychological status of DME patients with delayed anti-VEGF treatment during the pandemic.

    METHODS: A cross-sectional study was conducted from September 2020 to March 2021 in Ophthalmology Clinic Hospital Canselor Tuanku Muhriz Universiti Kebangsaan Malaysia (HCTM UKM). Subjects diagnosed with center-involved DME aged between 20 to 80 years who experienced delayed anti-VEGF injection were recruited. Level of depression, anxiety and stress were assessed using DASS-21 questionnaire. Statistical analysis using non-parametric tests were performed to determine the relationship between the DASS-21 score and duration of last injection, in those whose vision was affected by delayed injection and the relationship to the impact of COVID-19 pandemic. Statistical significance was denoted as p < 0.05.

    RESULTS: A total of 86 respondents with median age of 69 years old participated in this study. Most respondents were Malays (n = 47,54.7%) males (n = 51, 59.3%), had education up to secondary level (n = 37, 43%), unemployed (n = 78, 90.7%), married (n = 72, 83.7%) and living with their family (n = 82, 95.3%). The number of intravitreal injections received was at least three times among the respondents (n = 81, 94.2%). More than half of the respondents (n = 46, 53.5%) had been postponed for more than 12 weeks and felt that their vision was affected after delayed intravitreal injection (n = 47, 54.7%). Most of the subjects did not experience depression, anxiety, or stress. However, there was a significant level of stress scores among those with delayed injection of 9 to 12 weeks (p = 0.004), and significant anxiety (p = 0.029) and stress (p = 0.014) scores found in subjects with vision affected due to delayed treatment.

    CONCLUSION: The level of anxiety and stress can be significant in DME patients who experienced delay in intravitreal anti-VEGF treatment. Assessment of psychosocial impacts is important to identify early mental health issues potentially leading to the onset of psychiatry illness, thus early intervention is indispensable.

    Matched MeSH terms: Intravitreal Injections
  5. Myint KT, Sahoo S, Thein AW, Moe S, Ni H
    Cochrane Database Syst Rev, 2022 Dec 12;12(12):CD010790.
    PMID: 36508693 DOI: 10.1002/14651858.CD010790.pub3
    BACKGROUND: Sickle cell disease (SCD) includes a group of inherited haemoglobinopathies affecting multiple organs including the eyes. Some people with SCD develop ocular manifestations. Vision-threatening complications are mainly due to proliferative sickle retinopathy, which is characterised by proliferation of new blood vessels. Laser photocoagulation is widely applicable in proliferative retinopathies. It is important to evaluate the efficacy and safety of laser photocoagulation in the treatment of proliferative sickle retinopathy (PSR) to prevent sight-threatening complications.

    OBJECTIVES: To evaluate the effectiveness of various techniques of laser photocoagulation therapy in SCD-related proliferative retinopathy.

    SEARCH METHODS: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group's Haemoglobinopathies Trials Register, compiled from electronic database searches and handsearching of journals and conference abstract books. Date of last search: 4 July 2022. We also searched the following resources (26 June 2022): Latin American and Caribbean Health Science Literature Database (LILACS); WHO International Clinical Trials Registry Platforms (ICTRP); and ClinicalTrials.gov.

    SELECTION CRITERIA: Randomised controlled trials comparing laser photocoagulation to no treatment in children and adults with SCD.

    DATA COLLECTION AND ANALYSIS: Two review authors independently assessed eligibility and risk of bias of the included trials; we extracted and analysed data, contacting trial authors for additional information. We assessed the certainty of the evidence using the GRADE criteria.

    MAIN RESULTS: We included three trials (414 eyes of 339 children and adults) comparing the efficacy and safety of laser photocoagulation to no therapy in people with PSR. There were 160 males and 179 females ranging in age from 13 to 67 years. The trials used different laser photocoagulation techniques; one single-centre trial employed sectoral scatter laser photocoagulation using an argon laser; a two-centre trial employed feeder vessel coagulation using argon laser in one centre and xenon arc in the second centre; while a third trial employed focal scatter laser photocoagulation using argon laser. The mean follow-up periods were 21 to 32 months in one trial, 42 to 47 months in a second, and 48 months in the third. Two trials had a high risk of allocation bias due to the randomisation method for participants with bilateral disease; the third trial had an unclear risk of selection bias. One trial was at risk of reporting bias. Given the unit of analysis is the eye rather than the individual, we chose to report the data narratively. Using sectoral scatter laser photocoagulation, one trial (174 eyes) reported no difference between groups for complete regression of PSR: 30.2% in the laser group and 22.4% in the control group. The same trial also reported no difference between groups in the development of new PSR: 34.3% of lasered eyes and 41.3% of control eyes (very low-certainty evidence). The two-centre trial using feeder vessel coagulation, only presented data at follow-up for one centre (mean period of nine years) and reported the development of new sea fan in 48.0% in the treated and 45.0% in the control group; no statistical significance (P = 0.64). A third trial reported regression in 55% of the laser group versus 28.6% of controls and progression of PSR in 10.5% of treated versus 25.7% of control eyes. We graded the evidence for these two primary outcomes as very low-certainty evidence. The sectoral scatter laser photocoagulation trial reported visual loss in 3.0% of treated eyes (mean follow-up 47 months) versus 12.0% of controlled eyes (mean follow-up 42 months) (P = 0.019). The feeder vessel coagulation trial reported visual loss in 1.14% of the laser group and 7.5% of the control group (mean follow-up 26 months at one site and 32 months in another) (P = 0.07). The focal scatter laser photocoagulation trial (mean follow-up of four years) reported that 72/73 eyes had the same visual acuity, while visual loss was seen in only one eye from the control group. We graded the certainty of the evidence as very low. The sectoral scatter laser trial detected vitreous haemorrhage in 12.0% of the laser group and 25.3% of control with a mean follow-up of 42 (control) to 47 months (treated) (P ≤ 0.5). The two-centre feeder vessel coagulation trial observed vitreous haemorrhage in 3.4% treated eyes (mean follow-up 26 months) versus 27.5% control eyes (mean follow-up 32 months); one centre (mean follow-up nine years) reported vitreous haemorrhage in 1/25 eyes (4.0%) in the treatment group and 9/20 eyes (45.0%) in the control group (P = 0.002). The scatter laser photocoagulation trial reported that vitreous haemorrhage was not seen in the treated group compared to 6/35 (17.1%) eyes in the control group and appeared only in the grades B and (PSR) stage III) (P < 0.05). We graded evidence for this outcome as low-certainty. Regarding adverse effects, only one occurrence of retinal tear was reported. All three trials reported on retinal detachment, with no significance across the treatment and control groups (low-certainty evidence). One trial reported on choroidal neovascularization, with treatment with xenon arc found to be associated with a significantly higher risk, but visual loss related to this complication is uncommon with long-term follow-up of three years or more. The included trials did not report on other adverse effects or quality of life.

    AUTHORS' CONCLUSIONS: Our conclusions are based on the data from three trials (two of which were conducted over 30 years ago). Given the limited evidence available, which we assessed to be of low- or very low-certainty, we are uncertain whether laser therapy for sickle cell retinopathy improves the outcomes measured in this review. This treatment does not appear to have an effect on clinical outcomes such as regression of PSR and development of new incidences. No evidence is available assessing efficacy in relation to patient-important outcomes (such as quality of life or the loss of a driving licence).  Further research is needed to examine the safety of laser treatment compared to other interventions such as intravitreal injection of anti-vascular endothelial growth factors (VEGFs) . Patient-important outcomes as well as cost-effectiveness should be addressed.

    Matched MeSH terms: Intravitreal Injections
  6. Sim SS, Vyas CH, Gunatheesan R, Lott PW, Sun CZ, Teo KYC, et al.
    Eye (Lond), 2022 Jun;36(6):1142.
    PMID: 35001091 DOI: 10.1038/s41433-021-01874-7
    Matched MeSH terms: Intravitreal Injections
  7. Sakamoto T, Shimura M, Kitano S, Ohji M, Ogura Y, Yamashita H, et al.
    Graefes Arch Clin Exp Ophthalmol, 2022 Feb;260(2):477-487.
    PMID: 34477927 DOI: 10.1007/s00417-021-05308-8
    PURPOSE: The MERCURY study aimed to evaluate the effects on visual acuity and psychological symptoms, and safety, of ranibizumab and subsequent treatment in patients with diabetic macular oedema (DME) and impaired visual acuity (VA). We report data from the prespecified 12-month interim analysis.

    METHODS: This was a 24-month, phase 4, open-label, single-arm, prospective, observational study conducted at 20 specialised retinal centres in Japan. Participants were 209 patients with DME and impaired VA, not previously treated with either intravitreal or systemic anti-vascular endothelial growth factor (anti-VEGF) agents, who initiated ranibizumab 0.5 mg per investigator discretion. Following ranibizumab administration, patients were treated per routine clinical practice. Other treatments were allowed. The main outcome measure was the mean change in best-corrected VA (BCVA) in logarithmic minimum angle of resolution (logMAR) from baseline to month 12. An exploratory objective was to assess patients' psychological status using the Hospital Anxiety and Depression Scale (HADS).

    RESULTS: The mean ± standard deviation BCVA at baseline was 0.43 ± 0.39 logMAR. The mean number of injections of ranibizumab and anti-VEGF agents from baseline to month 11 was 3.2 ± 2.0 and 3.6 ± 2.4, respectively. The BCVA change from baseline to 12 months was - 0.08 ± 0.34 logMAR (p = 0.011), showing a significant improvement; the HADS-anxiety score also decreased significantly (p = 0.001) and the depression score decreased numerically (p = 0.080).

    CONCLUSION: MERCURY study data confirm the effectiveness of real-world treatment initiated with ranibizumab in Japanese patients with DME. In addition, treatment was able to positively influence anxiety via VA improvement.

    Matched MeSH terms: Intravitreal Injections
  8. Chaikitmongkol V, Sagong M, Lai TYY, Tan GSW, Ngah NF, Ohji M, et al.
    Asia Pac J Ophthalmol (Phila), 2021 Nov 24;10(6):507-518.
    PMID: 34839342 DOI: 10.1097/APO.0000000000000445
    PURPOSE: Review and provide consensus recommendations on use of treat-and-extend (T&E) regimens for neovascular age-related macular degeneration (nAMD) and polypoidal choroidal vasculopathy (PCV) management with relevance for clinicians in the Asia-Pacific region.

    METHODS: A systematic search of MEDLINE, EMBASE, and Cochrane databases, and abstract databases of the Asia-Pacific Vitreo-retina Society, European Society of Retina Specialists, American Academy of Ophthalmology, and Controversies in Ophthalmology: Asia-Australia congresses, was conducted to assess evidence for T&E regimens in nAMD. Only studies with ≥100 study eyes were included. An expert panel reviewed the results and key factors potentially influencing the use of T&E regimens in nAMD and PCV, and subsequently formed consensus recommendations for their application in the Asia-Pacific region.

    RESULTS: Twenty-seven studies were included. Studies demonstrated that T&E regimens with aflibercept, ranibizumab, or bevacizumab in nAMD, and with aflibercept in PCV, were efficacious and safe. The recommendation for T&E is, after ≥3 consecutive monthly loading doses, treatment intervals can be extended by 2 to 4 weeks up to 12 to 16 weeks. When disease activity recurs, the recommendation is to reinject and shorten intervals by 2 to 4 weeks until fluid resolution, after which treatment intervals can again be extended. Intraretinal fluid should be treated until resolved; however, persistent minimal subretinal fluid after consecutive treatments may be tolerated with treatment intervals maintained or extended if the clinical condition is stable.

    CONCLUSIONS: T&E regimens are efficacious and safe for nAMD and PCV, can reduce the number of visits, and minimize the overall burden for clinicians and patients.

    Matched MeSH terms: Intravitreal Injections
  9. Ghoshal R, Sharanjeet-Kaur S, Fadzil NM, Ghosh S, Ngah N, Aziz RAA
    PMID: 34070071 DOI: 10.3390/ijerph18105378
    Although optical coherence tomography (OCT) parameters have assisted in the diagnosis of polypoidal choroidal vasculopathy (PCV), its potential to evaluate treatment outcomes has not been established. The purpose of this pilot study was to evaluate baseline OCT parameters that may influence treatment outcome in PCV eyes with combination therapy. In this single-centered, prospective study, patients were recruited with at least one treatment-naïve PCV eye and treated with combination therapy of intravitreal anti-vascular endothelial growth factor and photodynamic therapy. Best-corrected distance and near visual acuity (DVA and NVA), and contrast sensitivity (CS) were recorded at baseline and six months after treatment. OCT parameters were determined. Twenty-six eyes of 26 patients aged between 51 to 83 years were evaluated. In eyes that had disrupted external limiting membrane (ELM), photoreceptors inner and outer segment (IS-OS) junction at 1000 micron of fovea at baseline showed low mean visual functions after 6 months of treatment. Eyes with foveal sub-retinal fluid (SRF) and polyp at central 1000 micron of fovea at baseline showed significantly worse DVA and CS after six months. Thus, the presence of foveal SRF, foveal polyp, disrupted ELM, and IS-OS junction at baseline significantly influenced the six months' visual outcome in PCV eyes treated with combination therapy.
    Matched MeSH terms: Intravitreal Injections
  10. Ghoshal R, Sharanjeet-Kaur S, Fadzil NM, Ghosh S, Ngah NF, Aziz RABA
    PMID: 33806713 DOI: 10.3390/ijerph18052581
    The objective of this study was to compare visual parameters and retinal layers' morphology pre-treatment (baseline) and 6 months post-treatment in polypoidal choroidal vasculopathy (PCV) eyes. A single centre, longitudinal, prospective study was conducted at a public tertiary hospital of Malaysia. Visual parameters including distance and near visual acuity (DVA and NVA), contrast sensitivity (CS), reading speed (RS), and different qualitative and quantitative optical coherence tomography (OCT) parameters were evaluated pre- and 6 months post-treatment. Thirty-three naïve PCV eyes of 32 patients (mean age of 67.62 years) were evaluated pre- and post-treatment of intravitreal ranibizumab with and without photodynamic therapy. After treatment, sub retinal fluid decreased from 27 eyes (84.35%) at baseline to 7 eyes (21.88%) at 6 months while pigment epithelium detachment decreased from 32 eyes (100%) at base line to 15 eyes (46.87%) at 6 months. Mean pre-treatment quantitative morphological OCT retinal parameters including thickness and volume of central sub field, center thickness, center minimum, and maximum thickness reduced significantly. Similarly, all visual parameters including DVA, NVA, CS, and RS showed statistically significant improvement. While 89% of the eyes showed improvement in CS, 78%, 71%, and 65% of the eyes showed improvement in NVA, RS, and DVA, respectively. Thus, CS was the most treatment responsive visual parameter.
    Matched MeSH terms: Intravitreal Injections
  11. Subbiah D, Hashim H, Chew FLM
    Ocul Immunol Inflamm, 2020 Oct 02;28(7):1149-1151.
    PMID: 31509457 DOI: 10.1080/09273948.2019.1648834
    We present five cases of choroidal neovascularization secondary to pediatric Best disease which were treated with two different doses of intravitreal ranibizumab. Optical coherence tomography was used for monitoring of the cases. Three cases had subretinal fibrosis at presentation and two out of these 3 cases required repeat intravitreal ranibizumab at one year follow-up due to recurrence of subfoveal subretinal fluid.
    Matched MeSH terms: Intravitreal Injections
  12. Sarojini K, Ling KP, Teh WM, Ali H, Zunaina E
    Cureus, 2020 Sep 07;12(9):e10297.
    PMID: 33047087 DOI: 10.7759/cureus.10297
    We report a case of optic disc drusen (ODD) associated with peripapillary polypoidal choroidal vasculopathy (PCV). A 62-year-old Malay lady presented with both eye ODD and the left eye associated with peripapillary subretinal hemorrhage. Ultrasound B-scan and red-free photography confirmed the optic nerve head drusen findings bilaterally. Optical coherence tomography (OCT) of the left eye showed sharply elevated peripapillary pigment epithelial detachment with subretinal fluid. The presence of peripapillary polyps with branching vascular network in indocyanine green angiography of the left eye further confirmed the diagnosis of PCV and excluded choroidal neovascularization (CNV) secondary to ODD. Subsequently, the patient was treated with a combination of verteporfin photodynamic therapy with three monthly intravitreal ranibizumab injections. Three months after the combined treatment, OCT showed completely resolved subretinal fluid. ODD can cause compression of the subretinal vessels at the optic disc that results in retinal ischemia and release of vascular endothelial growth factor, which may trigger the development of CNV or PCV. The rarity of this combination makes it interesting to study more cases of ODD with PCV. Importantly, a thorough evaluation in distinguishing the PCV from the CNV that mimics it is crucial for early detection and prompt intervention. In this case, indocyanine green angiography (ICGA) is the diagnostic method to differentiate the PCV from CNV secondary to ODD.
    Matched MeSH terms: Intravitreal Injections
  13. Lim TH, Lai TYY, Takahashi K, Wong TY, Chen LJ, Ruamviboonsuk P, et al.
    JAMA Ophthalmol, 2020 09 01;138(9):935-942.
    PMID: 32672800 DOI: 10.1001/jamaophthalmol.2020.2443
    Importance: The 2-year efficacy and safety of combination therapy of ranibizumab administered together with verteporfin photodynamic therapy (vPDT) compared with ranibizumab monotherapy in participants with polypoidal choroidal vasculopathy (PCV) are unclear.

    Objective: To compare treatment outcomes of ranibizumab, 0.5 mg, plus prompt vPDT combination therapy with ranibizumab, 0.5 mg, monotherapy in participants with PCV for 24 months.

    Design, Setting, and Participants: This 24-month, phase IV, double-masked, multicenter, randomized clinical trial (EVEREST II) was conducted among Asian participants from August 7, 2013, to March 2, 2017, with symptomatic macular PCV confirmed using indocyanine green angiography.

    Interventions: Participants (N = 322) were randomized 1:1 to ranibizumab, 0.5 mg, plus vPDT (combination therapy group; n = 168) or ranibizumab, 0.5 mg, plus sham PDT (monotherapy group; n = 154). All participants received 3 consecutive monthly ranibizumab injections, followed by a pro re nata regimen. Participants also received vPDT (combination group) or sham PDT (monotherapy group) on day 1, followed by a pro re nata regimen based on the presence of active polypoidal lesions.

    Main Outcomes and Measures: Evaluation of combination therapy vs monotherapy at 24 months in key clinical outcomes, treatment exposure, and safety. Polypoidal lesion regression was defined as the absence of indocyanine green hyperfluorescence of polypoidal lesions.

    Results: Among 322 participants (mean [SD] age, 68.1 [8.8] years; 225 [69.9%] male), the adjusted mean best-corrected visual acuity (BCVA) gains at month 24 were 9.6 letters in the combination therapy group and 5.5 letters in the monotherapy group (mean difference, 4.1 letters; 95% CI, 1.0-7.2 letters; P = .005), demonstrating that combination therapy was superior to monotherapy by the BCVA change from baseline to month 24. Combination therapy was superior to monotherapy in terms of complete polypoidal lesion regression at month 24 (81 of 143 [56.6%] vs 23 of 86 [26.7%] participants; P 

    Matched MeSH terms: Intravitreal Injections
  14. Nor Arfuzir NN, Agarwal R, Iezhitsa I, Agarwal P, Ismail NM
    Exp Eye Res, 2020 05;194:107996.
    PMID: 32156652 DOI: 10.1016/j.exer.2020.107996
    Endothelin-1 (ET-1), a potent vasoconstrictor, plays a significant role in the pathophysiology of ocular conditions like glaucoma. Glaucoma is characterized by apoptotic loss of retinal ganglion cells (RGCs) and loss of visual fields and is a leading cause of irreversible blindness. In glaucomatous eyes, retinal ischemia causes release of pro-inflammatory mediators such as interleukin (IL)-1β, IL-6 and tumor necrosis factor (TNF)-α and promotes activation of transcription factors such as nuclear factor kappa B (NFKB) and c-Jun. Magnesium acetyltaurate (MgAT) has previously been shown to protect against ET-1 induced retinal and optic nerve damage. Current study investigated the mechanisms underlying these effects of MgAT, which so far remain unknown. Sprague dawley rats were intravitreally injected with ET-1 with or without pretreatment with MgAT. Seven days post-injection, retinal expression of IL-1β, IL-6, TNF-α, NFKB and c-Jun protein and genes was determined using multiplex assay, Western blot and PCR. Animals were subjected to retrograde labeling of RGCs to determine the extent of RGC survival. RGC survival was also examined using Brn3A staining. Furthermore, visual functions of rats were determined using Morris water maze. It was observed that pre-treatment with MgAT protects against ET-1 induced increase in the retinal expression of IL-1β, IL-6 and TNF-α proteins and genes. It also protected against ET-1 induced activation of NFKB and c-Jun. These effects of MgAT were associated with greater RGC survival and preservation of visual functions in rats. In conclusion, MgAT prevents ET-1 induced RGC loss and loss of visual functions by suppressing neuroinflammatory reaction in rat retinas.
    Matched MeSH terms: Intravitreal Injections
  15. Chhablani J, Wong K, Tan GS, Sudhalkar A, Laude A, Cheung CMG, et al.
    Asia Pac J Ophthalmol (Phila), 2020;9(5):426-434.
    PMID: 32956188 DOI: 10.1097/APO.0000000000000312
    PURPOSE: The aim of this consensus article was to provide comprehensive recommendations in the management of diabetic macular edema (DME) by reviewing recent clinical evidence.

    DESIGN: A questionnaire containing 47 questions was developed which encompassed clinical scenarios such as treatment response to anti-vascular endothelial growth factor and steroid, treatment side effects, as well as cost and compliance/reimbursement in the management of DME using a Dephi questionnaire as guide.

    METHODS: An expert panel of 12 retinal specialists from Singapore, Malaysia, Philippines, India and Vietnam responded to this questionnaire on two separate occasions. The first round responses were compiled, analyzed and discussed in a round table discussion where a consensus was sought through voting. Consensus was considered achieved, when 9 of the 12 panellists (75%) agreed on a recommendation.

    RESULTS: The DME patients were initially profiled based on their response to treatment, and the terms target response, adequate response, nonresponse, and inadequate response were defined. The panellists arrived at a consensus on various aspects of DME treatment such as need for classification of patients before treatment, first-line treatment options, appropriate time to switch between treatment modalities, and steroid-related side effects based on which recommendations were derived, and a treatment algorithm was developed.

    CONCLUSIONS: This consensus article provides comprehensive, evidence-based treatment guidelines in the management of DME in Asian population. In addition, it also provides recommendations on other aspects of DME management such as steroid treatment for stable glaucoma patients, management of intraocular pressure rise, and recommendations for cataract development.

    Matched MeSH terms: Intravitreal Injections
  16. Jirjees F, Soliman K, Wang Y, Sonawane R, Sheshala R, Jones D, et al.
    J Pharm Biomed Anal, 2019 Sep 10;174:145-150.
    PMID: 31167158 DOI: 10.1016/j.jpba.2019.05.038
    Bevacizumab is a full-length human monoclonal antibody used to treat various neovascular diseases such as wet age-related macular degeneration (AMD), diabetic eye disease and other problems of the retina. Monthly intravitreal injections of bevacizumab (Avastin®) are effective in the treatment of wet AMD. However, there is a growing demand in the development of sustained release ophthalmic formulations. Therefore, this study aims, for the first time, to develop a rapid, simple, and sensitive method using size exclusion chromatography coupled with fluorescence detection for routine quantification of bevacizumab in ophthalmic formulations and during in vitro release studies. The selected chromatographic conditions included an aqueous mobile phase composed of 35 mM sodium phosphate buffer and 300 mM sodium chloride (pH 6.8), a flow rate of 0.5 mL/min, and the fluorescence detector was operated at excitation and emission wavelengths of 280 and 340 nm, respectively. The peak area-concentration relationship maintained its linearity over concentration range of 0.1-20 μg/mL (R2 = 0.9993), and the quantitation limit was 100 ng/mL. The method was validated for specificity, accuracy, precision, and robustness. The developed method had a run time of 6 min at temperature 25 °C, making it a unique validated method for rapid and cost-effective quantification of bevacizumab.
    Matched MeSH terms: Intravitreal Injections
  17. Yap JF, Wai YZ, Ng QX, Lim LT
    J Med Case Rep, 2019 May 06;13(1):131.
    PMID: 31056080 DOI: 10.1186/s13256-019-2064-1
    BACKGROUND: This is a case report of an iatrogenic intralenticular broken steroid (Ozurdex™) implant in a patient with uveitis. There are only a few case reports on broken Ozurdex™ implants in the vitreous cavity, with none of them involving the crystalline lens. A few authors have described the accidental injection of an Ozurdex™ implant into the crystalline lens, but all of the implants remained in one piece in the lens and none of them were broken. We report an unusual case of an Ozurdex™ implant which was injected inadvertently into the crystalline lens, resulting in a broken Ozurdex™ implant with an entry and exit wound through the posterior capsule of the lens.

    CASE PRESENTATION: An ophthalmic trainee performed an Ozurdex™ intravitreal injection into a 48-year-old Asian man's right eye under aseptic conditions. This patient was then followed up for further management. On day 7 post-procedure, a slit lamp examination revealed that the Ozurdex™ implant was injected into the intralenticular structure of his right eye and had fractured into two pieces. The posterior capsule of the right lens was breached, with one half of the Ozurdex™ implant stuck at the entry and the other stuck at the exit wound of the posterior capsule. This patient underwent right eye cataract extraction and repositioning of the fractured implant; he made an uneventful recovery.

    CONCLUSIONS: Ophthalmologists should be aware of the potential risk of injecting an Ozurdex™ implant into an anatomical structure other than the vitreous cavity. Adequate training and careful administration of the Ozurdex™ implant are necessary to avoid such a complication, which fortunately is rare.

    Matched MeSH terms: Intravitreal Injections
  18. Lambuk L, Iezhitsa I, Agarwal R, Bakar NS, Agarwal P, Ismail NM
    Neurotoxicology, 2019 01;70:62-71.
    PMID: 30385388 DOI: 10.1016/j.neuro.2018.10.009
    OBJECTIVE: N-methyl-D-aspartate (NMDA) excitotoxicity has been proposed to mediate apoptosis of retinal ganglion cells (RGCs) in glaucoma. Taurine (TAU) has been shown to have neuroprotective properties, thus we examined anti-apoptotic effect of TAU against retinal damage after NMDA exposure.

    METHODOLOGY: Sprague-Dawley rats were divided into 5 groups of 33 each. Group 1 was administered intravitreally with PBS and group 2 was similarly injected with NMDA (160 nmol). Groups 3, 4 and 5 were injected with TAU (320 nmol) 24 hours before (pre-treatment), in combination (co-treatment) and 24 hours after (post-treatment) NMDA exposure respectively. Seven days after injection, rats were sacrificed; eyes were enucleated, fixed and processed for morphometric analysis, TUNEL and caspase-3 staining. Optic nerve morphology assessment was done using toluidine blue staining. The estimation of BDNF, pro/anti-apoptotic factors (Bax/Bcl-2) and caspase-3 activity in retina was done using ELISA technique.

    RESULTS: Severe degenerative changes were observed in retinae after intravitreal NMDA exposure. The retinal morphology in the TAU pre-treated group appeared more similar to the control retinae and demonstrated a higher number of nuclei than the NMDA group both per 100 μm length (by 1.5-fold, p 

    Matched MeSH terms: Intravitreal Injections/methods*
  19. Mohamad NA, Ramachandran V, Ismail P, Mohd Isa H, Chan YM, Ngah NF, et al.
    Bosn J Basic Med Sci, 2018 Aug 01;18(3):260-267.
    PMID: 29579408 DOI: 10.17305/bjbms.2018.2493
    Pharmacogenetic studies indicate that a variable response to anti-vascular endothelial growth factor (VEGF) therapy in patients with neovascular form of AMD (nAMD) may be due to polymorphisms in the complement factor H gene (CFH). This study is the first to investigate the association between CFH Y402H polymorphism and the response to ranibizumab therapy in Malaysian patients with nAMD. We included 134 patients with nAMD, examined between September 2014 and February 2016. The diagnosis of nAMD was confirmed by ophthalmologic examination, before ranibizumab therapy was started. Each patient received an intravitreal injection of 0.5 mg/0.05 ml ranibizumab following a treat-and-extend (TE) regimen. Best-corrected visual acuity (BCVA) and central retinal thickness (CRT) were recorded after 3 and 6 months following the first injection and compared with the baseline values. Genotyping of Y402H (rs1061170) polymorphism was performed using PCR-RFLP and the amplified product was digested with MluCI restriction enzyme. Association between the Y402H genotypes and response to treatment was determined by a logistic regression analysis of responder (n = 49) and non-responder (n = 84) group. Significantly worse mean BCVA was observed for the CC genotype compared to the TT + CT genotype in the total sample after 6-month follow-up (p = 0.018). Comparing the baseline and 6-month point measurements, improved mean BCVA was observed in responder group, while worse mean BCVA was recorded for non-responder group. However, our regression analysis, adjusted for confounding factors, showed no significant association between the Y402H genotypes and response to treatment in nAMD patients under the recessive model (p > 0.05). Overall, our results suggest that factors other than Y402H polymorphism may be involved in the progression of nAMD after treatment with anti-VEGF agents, in Malaysian population.
    Matched MeSH terms: Intravitreal Injections
  20. Nor Arfuzir NN, Agarwal R, Iezhitsa I, Agarwal P, Sidek S, Spasov A, et al.
    Curr Eye Res, 2018 08;43(8):1032-1040.
    PMID: 29676937 DOI: 10.1080/02713683.2018.1467933
    PURPOSE: Retinal ganglion cell apoptosis in glaucoma is associated with elevated levels of endothelin-1 (ET1), a potent vasoconstrictor. ET1-induced retinal ischemia leads to altered expression of nitric oxide synthase (NOS) isoforms leading to increased formation of nitric oxide (NO) and retinal nitrosative stress. Since magnesium (Mg) is known to improve endothelial functions and reduce oxidative stress and taurine (TAU) possesses potent antioxidant properties, we investigated the protective effects of magnesium acetyltaurate (MgAT) against ET1-induced nitrosative stress and retinal damage in rats. We also compared the effects of MgAT with that of TAU alone.

    METHODS: Sprague Dawley rats were intravitreally injected with ET1. MgAT and TAU were administered as pre-, co-, or posttreatment. Subsequently, the expression of NOS isoforms was detected in retina by immunohistochemistry, retinal nitrotyrosine level was estimated using ELISA, and retinal cell apoptosis was detected by TUNEL staining.

    RESULTS: Intravitreal ET1 caused a significant increase in the expressions of nNOS and iNOS while eNOS expression was significantly reduced compared to vehicle treated group. Administration of both MgAT and TAU restored the altered levels of NOS isoform expression, reduced retinal nitrosative stress and retinal cell apoptosis. The effect of MgAT, however, was greater than that of TAU alone.

    CONCLUSIONS: MgAT and TAU prevent ET1-induced retinal cell apoptosis by reducing retinal nitrosative stress in Sprague Dawley rats. Addition of TAU to Mg seems to enhance the efficacy of TAU compared to when given alone. Moreover, the pretreatment with MgAT/TAU showed higher efficacy compared to co- or posttreatment.

    Matched MeSH terms: Intravitreal Injections
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