Browsing by Author "Bracha, Peter"

Now showing 1 - 7 of 7
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    The acute and chronic effects of intravitreal anti-vascular endothelial growth factor injections on intraocular pressure: A review
    (Elsevier, 2017) Bracha, Peter; Moore, Nicholas A.; Ciulla, Thomas A.; WuDunn, Darrell; Cantor, Louis B.; Department of Ophthalmology, School of Medicine
    The acute and chronic effects of repeated intravitreal antivascular endothelial growth factor (VEGF) injections on intraocular pressure have not been fully characterized, and the development of sustained ocular hypertension could adversely affect patients who are at risk of glaucomatous optic neuropathy. As expected, volume-driven, acute ocular hypertension immediately follows intravitreal injection, but this pressure elevation is generally transient and well tolerated. Several medications have been investigated to limit acute ocular hypertension following anti-VEGF therapy, but the benefits of pretreatment are not conclusive. Chronic, sustained ocular hypertension, distinct from the short-term acute ocular hypertension after each injection, has also been associated with repeated intravitreal anti-VEGF injections. Risk factors for chronic ocular hypertension include the total number of injections, a greater frequency of injection, and preexisting glaucoma. Proposed mechanisms for chronic ocular hypertension include microparticle obstruction, toxic or inflammatory effects on trabecular meshwork, as well as alterations in outflow facility by anti-VEGF agents. Although limiting anti-VEGF therapy could minimize the risk of both acute and chronic ocular hypertension, foregoing anti-VEGF therapy risks progression of various macular diseases with resulting permanent central vision loss. While definitive evidence of damage to the retinal nerve fiber layer is lacking, patients receiving repeated injections should be monitored for ocular hypertension and patients in whom sustained ocular hypertension subsequently developed should be periodically monitored for glaucomatous changes with optic nerve optical coherence tomography and static visual fields.
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    Gene Therapy for Inherited Retinal and Optic Nerve Degenerations
    (Taylor & Francis, 2018) Moore, Nicholas A.; Morral, Nuria; Ciulla, Thomas A.; Bracha, Peter; Ophthalmology, School of Medicine
    Introduction: The eye is a target for investigational gene therapy due to the monogenic nature of many inherited retinal and optic nerve degenerations (IRD), its accessibility, tight blood-ocular barrier, the ability to non-invasively monitor for functional and anatomic outcomes, as well as its relative immune privileged state.Vectors currently used in IRD clinical trials include adeno-associated virus (AAV), small single-stranded DNA viruses, and lentivirus, RNA viruses of the retrovirus family. Both can transduce non-dividing cells, but AAV are non-integrating, while lentivirus integrate into the host cell genome, and have a larger transgene capacity. Areas covered: This review covers Leber’s congenital amaurosis, choroideremia, retinitis pigmentosa, Usher syndrome, Stargardt disease, Leber’s hereditary optic neuropathy, Achromatopsia, and X-linked retinoschisis. Expert opinion: Despite great potential, gene therapy for IRD raises many questions, including the potential for less invasive intravitreal versus subretinal delivery, efficacy, safety, and longevity of response, as well as acceptance of novel study endpoints by regulatory bodies, patients, clinicians, and payers. Also, ultimate adoption of gene therapy for IRD will require widespread genetic screening to identify and diagnose patients based on genotype instead of phenotype.
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    Induced pluripotent stem cell-based therapy for age-related macular degeneration
    (Taylor & Francis, 2017) Bracha, Peter; Moore, Nicholas A.; Ciulla, Thomas A.; Ophthalmology, School of Medicine
    Introduction: In age-related macular degeneration (AMD), stem cells could possibly replace or regenerate disrupted pathologic retinal pigment epithelium (RPE), and produce supportive growth factors and cytokines such as brain-derived neurotrophic factor. Induced pluripotent stem cells (iPSCs)-derived RPE was first subretinally transplanted in a neovascular AMD patient in 2014. Areas covered: Induced PSCs are derived from the introduction of transcription factors to adult cells under specific cell culture conditions, followed by differentiation into RPE cells. Induced PSC-derived RPE cells exhibit ion transport, membrane potential, polarized VEGF secretion and gene expression that is similar to native RPE. Despite having similar in vitro function, morphology, immunostaining and microscopic analysis, it remains to be seen if iPSC-derived RPE can replicate the myriad of in vivo functions, including immunomodulatory effects, of native RPE cells. Historically, adjuvant RPE transplantation during CNV resections were technically difficult and complicated by immune rejection. Autologous iPSCs are hypothesized to reduce the risk of immune rejection, but their production is time-consuming and expensive. Alternatively, allogenic transplantation using human leukocyte antigen (HLA)-matched iPSCs, similar to HLA-matched organ transplantation, is currently being investigated. Expert opinion: Challenges to successful transplantation with iPSCs include surgical technique, a pathologic subretinal microenvironment, possible immune rejection, and complications of immunosuppression.
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    Intravitreal sirolimus for persistent, exudative age-related macular degeneration: a Pilot Study
    (BMC, 2021-02-16) Minturn, Robert J.; Bracha, Peter; Klein, Margaret J.; Chhablani, Jay; Harless, Ashley M.; Maturi, Raj K.; Ophthalmology, School of Medicine
    Background and objective: To evaluate the safety and efficacy of intravitreal sirolimus for persistent, exudative age-related macular degeneration (AMD). Methods: This institutional review board approved, registered (NCT02357342), prospective, subject-masked, single center, randomized controlled trial in subjects with persistent, exudative Age-related macular degeneration compared intravitreal sirolimus monotherapy (every 2 months) versus monthly anti-vascular endothelial growth factor (VEGF) over six months. Results: 20 subjects were randomized to each arm of the trial. Upon completion of the trial 20 patients were analyzed in the control (anti-vascular endothelial growth factor) group and 17 patients were analyzed in the treatment (sirolimus) group. On average, subjects had 33 previous anti-VEGF injections prior to entry. The primary end-point, mean central subfield thickness (CST), increased by 20 µm in the anti-vascular endothelial growth factor group and decreased by 40 µm in the sirolimus group (p = 0.03). Visual acuity outcomes were similar between groups. Serious ocular adverse events in the sirolimus group included one subject each with anterior uveitis, central retinal artery occlusion and subretinal hemorrhage. Conclusion: Monotherapy with intravitreal sirolimus for subjects with persistent, exudative age-related macular degeneration appears to have a limited positive anatomic benefit. The presence of adverse events in the experimental group merits further evaluation, potentially as an adjuvant therapy. Trial registration This trial was registered with the clinicaltrials.gov, NCT02357342, and was approved by the institutional review board at Advarra. Funding was provided by an investigator-initiated grant from Santen. Santen played no role in the design or implementation of this study.
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    Intravitreal sirolimus with adjunct aflibercept versus aflibercept monotherapy for persistent, exudative age-related macular degeneration: a pilot study
    (BMC, 2023-01-05) Rowe, Lucas W.; Minturn, Robert J.; Burgett, Lauren A.; Bracha, Peter; Maturi, Raj K.; Ophthalmology, School of Medicine
    Background: To determine the safety and efficacy of intravitreal sirolimus and adjunct aflibercept in subjects with persistent, exudative age-related macular degeneration despite previous intravitreal anti-vascular endothelial growth factor (VEGF) treatment. Methods: This institutional review board approved, registered (NCT02732899), prospective, subject-masked, single center, randomized controlled trial in subjects with persistent, exudative age-related macular degeneration compared alternating monthly intravitreal sirolimus and aflibercept (combination) versus aflibercept monotherapy (control) every 2 months over the course of 36 weeks. The primary measure of efficacy in the study was the mean change in central subfield thickness. Results: 20 subjects were enrolled in the study, with 10 subjects assigned to each treatment group. Subjects had an average of 38 previous anti-VEGF injections. Mean central subfield thickness decreased in the combination group by 54.0 μm compared to 0.1 μm in the control group (p = 0.28). Mean visual acuity improved in the combination group by 2.5 ETDRS letters versus 0.8 ETDRS letters in the control group (p = 0.42). There were no serious ocular adverse events in either group; however, there were three serious systemic events in the combination group, including hospitalizations due to pancreatitis, pneumonia, and worsening hypertension. Conclusion: There was no statistically significant difference in the mean central subfield thickness change between the combination and control groups. However, intravitreal sirolimus with adjunct aflibercept did appear to have potential anatomical benefits as a treatment for persistent, exudative age-related macular degeneration and requires further investigation with a larger cohort to better understand the potential risks and benefits.
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    Microbial Spectrum and Antibacterial Susceptibility of Endophthalmitis Cultures in a Tertiary Referral Center in the Midwestern United States: An Analysis From 295 Patients
    (Sage, 2020-09-22) Gemayel, Michael; Neiweem, Ashley; Aebi, Brent; Bracha, Peter; Ciulla, Thomas; Ophthalmology, School of Medicine
    Purpose: This work evaluates the microbial spectrum and antibiotic susceptibility pattern of endophthalmitis cases in a large tertiary referral center in the Midwestern United States. Methods: This retrospective case series included patients with clinically diagnosed endophthalmitis between April 14, 2006 and April 14, 2016, in whom ocular samples were submitted to the Microbiology Department at Indiana University. The patients were assessed by 11 vitreoretinal surgeons from 6 different sites in Indianapolis, including Indiana University and private practices, who receive patients from urban, suburban, and rural agricultural areas. Submitted specimens were cultured with the following media: blood agar, chocolate agar, MacConkey agar, and thioglycolate broth. Results: A total of 327 specimens from 295 patients were analyzed, with 96 (32.5%) samples from 90 (30.5%) patients meeting the criteria of confirmed growth. Of these 96 positive specimens, 83 (86.5%) organisms were identified as bacterial, and 13 (13.5%) were identified as fungal. Coagulase-negative Staphylococcus was the most common isolate (37.5%). Fifty gram-positive isolates and 10 gram-negative isolates underwent susceptibility testing. All 40 of the gram-positive isolates tested for vancomycin sensitivity were susceptible, whereas all 7 of the gram-negative isolates tested for ceftazidime sensitivity were susceptible. Conclusions: Empiric treatment with vancomycin and ceftazidime remains appropriate in most cases of endophthalmitis in the Midwestern United States, with 100% susceptibility of bacterial organisms tested with these antibiotics in this series. The high fungal culture rates in this study highlight the utility of obtaining vitreous cultures and potential need for antifungal agents in suspicious cases.
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    Vital Dyes in Vitreomacular Surgery
    (Slack, 2018) Bracha, Peter; Ciulla, Tom A.; Baumal, Caroline R.; Ophthalmology, School of Medicine
    Vital dyes contain complex molecules with chromophores that stain living tissues and have greatly enhanced identification and removal of transparent vitreoretinal tissues during surgery. Several “chromovitrectomy” dyes are frequently used by vitreoretinal specialists, including indocyanine green, trypan blue, brilliant blue G, and triamcinolone acetonide; other dyes are also under investigation. Trypan Blue was approved by the U.S. Food and Drug Administration (FDA) for epiretinal membrane removal, and preservative-free triamcinolone acetonide was approved by the FDA for intraocular use. However, currently available chromovitrectomy dyes have their limitations, and of particular concern for some of them is the possibility for acute and chronic toxicity to the neurosensory retina and retinal pigmented epithelium. The potentially irreversible acute toxicity and other limitations, such as lack of long-term safety profiles, highlight the need for further advancements.