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1.
Cochrane Database Syst Rev ; 12: CD012742, 2018 12 16.
Artigo em Inglês | MEDLINE | ID: mdl-30554418

RESUMO

BACKGROUND: Glaucoma is a leading cause of irreversible blindness. Subconjunctival draining minimally-invasive glaucoma devices such as the Xen gelatin implant and InnFocus stent have been introduced as a treatment to prevent glaucoma progressing.These implants provide a channel to allow aqueous humour from the anterior chamber of the eye to drain into the subconjunctival space on the surface of the eye thus reducing intraocular pressure (IOP) and mimicking the mechanism of the most commonly undertaken glaucoma surgery, trabeculectomy. OBJECTIVES: To evaluate the efficacy and safety of subconjunctival draining minimally-invasive glaucoma devices in treating people with open angle glaucoma and ocular hypertension whose condition is inadequately controlled with drops. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL; which contains the Cochrane Eyes and Vision Trials Register; 2018, Issue 6); Ovid MEDLINE; Ovid Embase; the ISRCTN registry; ClinicalTrials.gov and the WHO ICTRP. The date of the search was 10 July 2018. SELECTION CRITERIA: We searched for randomised controlled trials (RCTs) of Xen gelatin implant or InnFocus MicroShunt to other surgical treatments (other minimally-invasive glaucoma device techniques, trabeculectomy), laser treatment or medical treatment. We also planned to include trials where these devices were combined with phacoemulsification compared to phacoemulsification alone. DATA COLLECTION AND ANALYSIS: We planned to have two review authors independently extract data from reports of included studies using a data collection form and analyse data based on methods expected by Cochrane. Our primary outcome was mean change in IOP. Secondary outcomes included proportion of participants who were drop-free; proportion of participants who achieved an IOP of 21 mmHg or less, 17 mmHg or less or 14 mmHg or less; and proportion of participants experiencing intra- and postoperative complications. We planned to measure all outcomes in the short-term (six to 18 months), medium-term (18 to 36 months), and long-term (36 months onwards). MAIN RESULTS: We found no completed RCTs that met our inclusion criteria. We found one ongoing study (NCT01881425). The study compares InnFocus MicroShunt to trabeculectomy in people with primary open angle glaucoma. The primary outcome is greater than 20% IOP reduction from baseline to 12 months' follow-up. A total of 889 people aged between 40 and 85 years have been enrolled. The estimated study completion date is November 2019. AUTHORS' CONCLUSIONS: There is currently no high-quality evidence for the effects of subconjunctival draining minimally-invasive glaucoma devices for medically uncontrolled open angle glaucoma. Properly designed RCTs are needed to assess the medium- and long-term efficacy and safety of this technique.


Assuntos
Implantes para Drenagem de Glaucoma , Glaucoma/terapia , Implantes para Drenagem de Glaucoma/efeitos adversos , Humanos , Pressão Intraocular , Trabeculectomia
2.
Clin Exp Ophthalmol ; 43(9): 796-802, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26016558

RESUMO

BACKGROUND: This aims to determine the immediate and short-term risk of intraocular pressure spikes following diode laser cyclophotocoagulation. DESIGN: This study is a prospective, consecutive cohort study in a UK teaching hospital. PARTICIPANTS: Fifty-three consecutive patients undergoing cyclophotocoagulation were invited to participate in this study. METHODS: Intraocular pressure (IOP) measurements were taken immediately prior to cyclodiode laser, hourly for the first 3 h after laser, on the first and seventh postoperative days, and at three months following laser. MAIN OUTCOME MEASURES: Eyes experiencing intraocular pressure elevation defined at two levels (≥3 mm Hg and ≥10 mm Hg from the pretreatment level) were identified. RESULTS: Seventeen eyes (34%) had an elevation in intraocular pressure (≥3 mmHg) during the first 3 h postoperatively with a mean increase of 10.3 mmHg. No preoperative or perioperative associations were found for a postcyclodiode spike within the first 3 postoperative hours.No association was found between pressure spikes and visual acuity, reduction of glaucoma medication or final postoperative intraocular pressure at 3 months. Eyes that did not have an IOP spike during the first 3 h postoperatively had a greater reduction in IOP at 3 months (15.2 mmHg vs. 10.2 mmHg; P = 0.184). CONCLUSION: IOP spikes are common in the immediate period after cyclophotocoagulation. An elevation in IOP is noted after the first hour in the vast majority who experience a spike in the first 3 h post-procedure.


Assuntos
Corpo Ciliar/cirurgia , Glaucoma/cirurgia , Pressão Intraocular/fisiologia , Fotocoagulação a Laser/métodos , Lasers Semicondutores/uso terapêutico , Glaucoma/fisiopatologia , Hospitais de Ensino , Humanos , Estudos Prospectivos , Fatores de Tempo , Tonometria Ocular , Acuidade Visual/fisiologia
3.
Doc Ophthalmol ; 127(2): 165-71, 2013 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-23794161

RESUMO

BACKGROUND: To present a case of melanoma-associated retinopathy (MAR) which manifested 26 months prior to a formal diagnosis of melanoma. METHODS: Case report. RESULTS: A 72-year-old female presented with bilateral continuous photopsia consistent with MAR of 7-months duration. At this point, visual function appeared normal with the exception of mildly impaired colour vision (10/17 Ishihara plates). The flash electroretinographic (ERG) revealed extinguished rod responses, a normal a-wave and reduced b-wave (electronegative ERG) on the maximal combined response, absent oscillatory potentials and broadened a-wave trough on the cone response. Multifocal ERG (mfERG) responses were delayed and demonstrated atypical morphology. Nineteen months after the initial presentation, her visual symptoms had progressed significantly with constant debilitating photopsia in combination with 13 kg weight loss. Biopsy of a now evident left axillary mass demonstrated a metastatic high-grade malignant melanoma. No primary was detected, and an axillary lymph node clearance was undertaken. Subsequently, visual symptoms resolved with corresponding improvement in the ERG over the next 18 months. Rod responses recovered such that the amplitude was at the lower limit of normal and the mfERG response delay lessened. Unfortunately, the melanoma recurred and the patient passed away 6 months later. Visual symptoms did not recur. CONCLUSION: We present a case which demonstrates MAR may precede the formal diagnosis of melanoma by up to 26 months. The potential for improvement in the rod visual function persists over a period of years with normalisation of an electronegative waveform. In this case, cytoreductive surgery resulted in complete resolution of the MAR, which did not return even with a recurrence of the tumour.


Assuntos
Melanoma/secundário , Síndromes Paraneoplásicas Oculares/diagnóstico , Neoplasias Cutâneas/patologia , Idoso , Axila , Eletrorretinografia , Evolução Fatal , Feminino , Humanos , Excisão de Linfonodo , Linfonodos/patologia , Metástase Linfática , Síndromes Paraneoplásicas Oculares/fisiopatologia , Síndromes Paraneoplásicas Oculares/cirurgia , Estimulação Luminosa , Células Fotorreceptoras Retinianas Bastonetes/fisiologia , Acuidade Visual
4.
Optom Vis Sci ; 90(7): 691-9, 2013 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-23770655

RESUMO

PURPOSE: To assess the repeatability of Goldmann-correlated intraocular pressure (IOPG), corneal-compensated IOP (IOPCC), corneal hysteresis (CH), and the corneal resistance factor (CRF) obtained with the Ocular Response Analyzer (ORA) in normal eyes and to determine whether any differences in corneal biomechanical parameters or their repeatability exist between the sexes. METHODS: A prospective observational study assessing 100 normal adults (50 men and 50 women; median age, 54.5 years). Comparison of ORA parameters measured in both eyes in three sets of four consecutive readings by one examiner within a 30-minute period. RESULTS: The mean values of the ORA parameters assessed, the intraclass correlation coefficient (ICC) and the coefficient of repeatability (CR), were as follows for the right eye (n = 100): IOPG, 16.2 ± 3.3 mm Hg (ICC, 0.96; CR, 6.37); IOPCC, 16.2 ± 3.2 (ICC, 0.94; CR, 6.29); CRF, 10.9 ± 1.9 (ICC, 0.91; CR, 3.62); CH, 10.6 ± 1.7 (ICC, 0.94; CR, 3.37). The ICC between the readings was excellent (>0.9) for all the ORA parameters in both sexes, with the exception of one group (female CRF ICC, 0.86). Coefficient of repeatability of the instrument satisfies the British Standards Institution criteria for repeatability. There were no significant differences between corneal biomechanical factors and IOP results for men and women. CONCLUSIONS: Corneal biomechanical parameters measured by the ORA provide repeatable results in normal eyes, with no significant difference between the sexes.


Assuntos
Córnea/fisiologia , Elasticidade/fisiologia , Pressão Intraocular/fisiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Reprodutibilidade dos Testes , Fatores Sexuais , Tonometria Ocular/métodos , Adulto Jovem
5.
Int J Ophthalmol ; 16(4): 652-655, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37077484

RESUMO

AIM: To describe a case of aqueous misdirection complicated by subsequent persistent choroidal effusions following implantation of a Preserflo MicroShunt (PMS) device to treat advanced closed angle glaucoma. METHODS: A 67-year-old caucasian female with advanced primary angle-closure glaucoma on four medications with an intraocular pressure (IOP) of 26 mm Hg was listed for a PMS insertion with mitomycin C (MMC). RESULTS: Past ocular history was significant for pseudophakia and previous yttrium aluminum garnet (YAG) peripheral iridotomy. Surgery was uneventful but on the first postoperative day, she developed aqueous misdirection complicated by subsequent development of persistent uveal effusions. Conventional treatment strategies including atropine drops, YAG hyaloidotomy and choroidal effusion drainage proved ineffective. A combination of oral steroids and pars plana vitrectomy (PPV) along with an irido-zonulo-hyloidectomy (IZH) proved efficacious. CONCLUSION: To the best of the author's knowledge, this is the first published case of aqueous misdirection complicated with the presence of significant, unresolving choroidal effusions, highlighting the possibility and sequelae of comorbid pathology in nanophthalmic eyes.

6.
Br J Ophthalmol ; 107(8): 1104-1111, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-35365491

RESUMO

BACKGROUND/AIMS: To evaluate the efficacy and safety of the PreserFlo MicroShunt glaucoma device in a multicentre cohort study. METHODS: All consecutive patients who received the microshunt with mitomycin-C (MMC) 0.4 mg/mL from May 2019 to September 2020 in three UK tertiary centres. Primary outcome at 1 year was a complete success, with failure defined as intraocular pressure (IOP) >21 mmHg or <20% reduction, IOP≤5 mmHg with any decreased vision on two consecutive visits, reoperation or loss of light perception vision. Secondary outcomes were IOP, best-corrected visual acuity, medications, complications, interventions and reoperations. We also performed subgroup analyses for severe glaucoma and assessed risk factors for failure. RESULTS: 104 eyes had 1-year follow-up. Complete and qualified success at 1 year were achieved in 51.9% (N=54) and 16.4% (N=17), respectively, and failure occurred in 31.7% (N=33). There was a significant reduction in IOP (mmHg) from preoperatively (23.4±0.8, N=104) to 12 months (14.7±0.6, N=104) (p<0.0001). Antiglaucoma medications also decreased from preoperatively (3.4±0.1, N=104) to 12 months (0.7±0.1, N=104) (p<0.0001). Multivariate analyses showed an association between higher mean deviation and failure (HR 1.055, 95% CI 1.0075 to 1.11, p=0.0227). Complications were hypotony (19.2%; N=20), choroidal detachments (10.6%; N=11), hyphaema (5.8%; N=6) and bleb leak (5.8%; N=6). Needling and 5-fluorouracil injections were performed in 12.5% (N=13) and 33.7% (N=35), respectively, and 11.5% (N=12) required revision surgery. CONCLUSION: The PreserFlo MicroShunt with MMC 0.4 mg/mL showed an overall success rate of 68.3% at 1 year, and led to significant IOP and medication reduction with a low rate of adverse effects.


Assuntos
Glaucoma , Trabeculectomia , Humanos , Estudos de Coortes , Trabeculectomia/efeitos adversos , Glaucoma/tratamento farmacológico , Pressão Intraocular , Mitomicina/uso terapêutico , Resultado do Tratamento , Estudos Retrospectivos
7.
N Engl J Med ; 361(19): 1848-55, 2009 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-19890127

RESUMO

BACKGROUND: We investigated whether a novel, synthetic, peptide-based erythropoietin-receptor agonist (Hematide, Affymax) can stimulate erythropoiesis in patients with anemia that is caused by antierythropoietin antibodies. METHODS: In this open-label, single-group trial, we enrolled patients with chronic kidney disease who had pure red-cell aplasia or hypoplasia due to antierythropoietin antibodies and treated them with a synthetic peptide-based erythropoietin-receptor agonist. The agonist was administered by subcutaneous injection at an initial dose of 0.05 mg per kilogram of body weight every 4 weeks. The primary end point was a hemoglobin concentration above 11 g per deciliter without the need for transfusions. RESULTS: We treated 14 patients with the peptide agonist for a median of 28 months. The median hemoglobin concentration increased from 9.0 g per deciliter (with transfusion support in the case of 12 patients) before treatment to 11.4 g per deciliter at the time of the last administration of the agonist; transfusion requirements diminished within 12 weeks after the first dose, after which 13 of the 14 patients no longer required regular transfusions. Peak reticulocyte counts increased from a median of 10x10(9) per liter before treatment to peak counts of greater than 100x10(9) per liter. The level of antierythropoietin antibodies declined over the course of the study and became undetectable in six patients. One patient who initially responded to treatment had a diminished hematologic response a few months later despite increased doses of the agonist and required transfusions again; this patient was found to have antibodies against the agonist. One patient died 4 months after the last dose of the agonist, and a grade 3 or 4 adverse event occurred in seven other patients during the study period. CONCLUSIONS: This novel agonist of the erythropoietin receptor can correct anemia in patients with pure red-cell aplasia caused by antierythropoietin antibodies. (ClinicalTrials.gov number, NCT00314795.).


Assuntos
Receptores da Eritropoetina/agonistas , Aplasia Pura de Série Vermelha/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Autoanticorpos/sangue , Transfusão de Eritrócitos/estatística & dados numéricos , Eritropoetina/efeitos adversos , Eritropoetina/imunologia , Feminino , Hemoglobinas/análise , Humanos , Masculino , Pessoa de Meia-Idade , Proteínas Recombinantes , Aplasia Pura de Série Vermelha/etiologia , Aplasia Pura de Série Vermelha/terapia , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/imunologia
8.
Indian J Ophthalmol ; 70(6): 2180-2182, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35648009

RESUMO

We present a case of advanced glaucoma with previously failed trabeculectomy who underwent a Baerveldt tube (BVT) insertion, with initial success. However, 9 months post BVT insertion he developed profound clinically significant hypotony. Two attempts at controlling this with suture exchange led to episodes of significant ocular hypertension, followed by hypotony each time. We describe a technique of using a cut segment of the novel, polystyrene-block-isobutylene-block- styrene (SIBs) based Preserflo Microshunt (Santen Inc., Miami, FL) inserted into the tip of a BVT to control late onset hypotony with success. IOP at 6 weeks was 12mmHg on two drops with complete resolution of the choroidal maculopathy.


Assuntos
Implantes para Drenagem de Glaucoma , Glaucoma , Hipotensão Ocular , Trabeculectomia , Glaucoma/cirurgia , Implantes para Drenagem de Glaucoma/efeitos adversos , Humanos , Pressão Intraocular , Masculino , Hipotensão Ocular/diagnóstico , Hipotensão Ocular/etiologia , Hipotensão Ocular/cirurgia
9.
Clin Exp Ophthalmol ; 39(9): 858-64, 2011 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-21631674

RESUMO

BACKGROUND: Recent National Institute of Clinical Excellence guidance suggests primary surgery should be offered to patients presenting with glaucoma with severe visual field loss. We undertook a survey of UK consultant ophthalmologists to determine if this represents current practice and explore attitudes towards managing patients with advanced glaucoma at presentation. DESIGN: Questionnaire evaluation study. PARTICIPANTS: All consultant ophthalmologists currently practicing in the UK. METHODS: A single-page questionnaire was posted to all consultants (n = 910) currently practicing in the UK along with a pre-paid return envelope. A second questionnaire was sent to non-responders (n = 459). MAIN OUTCOME MEASURES: Questionnaire responses. RESULTS: 626 responses were received representing 68.8% of the population surveyed. 152 (24%) volunteered a specialist interest in glaucoma. Consensus opinion for both glaucoma specialists (64.9%) and non-glaucoma specialists (62.4%) was to start with primary medical therapy, most commonly citing surgical risk as the primary reason (23% and 22%, respectively) for this approach. Most felt the highest intraocular pressure measurement during follow up (measured in clinic) was the most important variable for prevention of further visual loss (60% of glaucoma specialists and 55% of non-glaucoma specialists). Eighty-three per cent of all responders suggested they would change their practice if evidence supporting primary surgery as a safe and more effective approach existed. CONCLUSIONS: Recent National Institute of Clinical Excellence guidance does not reflect the current management approach of UK ophthalmologists. The primary concern was related to potential complications of surgery although most practitioners would be willing to change their practice if evidence existed supporting primary surgery in patients presenting with advanced glaucoma.


Assuntos
Atitude do Pessoal de Saúde , Glaucoma de Ângulo Aberto/diagnóstico , Glaucoma de Ângulo Aberto/terapia , Oftalmologia , Padrões de Prática Médica/estatística & dados numéricos , Transtornos da Visão/diagnóstico , Campos Visuais , Anti-Hipertensivos/uso terapêutico , Consultores/estatística & dados numéricos , Inquéritos Epidemiológicos , Humanos , Pressão Intraocular , Inquéritos e Questionários , Trabeculectomia/estatística & dados numéricos , Reino Unido , Transtornos da Visão/reabilitação , Recursos Humanos
10.
Eye (Lond) ; 35(6): 1644-1650, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32839558

RESUMO

BACKGROUND: Registration as sight impaired allows access to services important for patients. The rates of sight impairment due to visual field loss are underestimated. Previous work has shown that evaluation of visual field defects in both eyes produces poor agreement among ophthalmologists for categorisation of patients as eligible for sight impairment registration. AIM: To evaluate the impact of binocular summation of both eye glaucomatous visual field defects on agreement for sight impairment registration. METHODS: Thirty consultant ophthalmologists (Graders), graded 50 glaucomatous visual field sets. Each consisted of both monocular fields and summated binocular plots. Graders classified the visual field sets as sight impaired (SI), severely sight impaired (SSI) or neither. Trichotomous, (SI, SSI or no sight impairment) and dichotomous (any sight impairment versus no sight impairment) concordance values were estimated for the group of graders as a whole and for glaucoma and non-glaucoma experts. RESULTS: For trichotomous analysis the overall kappa agreement rate was 0.29; for dichotomous analysis it was 0.40. There was no material difference between glaucoma experts and non-experts. CONCLUSION: Overall agreement was modest. Grading for SI showed the poorest levels of agreement. Using binocular fields does not appear to improve concordance for sight impairment registration. Moreover, there is no difference in agreement between glaucoma and non-glaucoma experts. An overall score for visual disability using mean deviation may be a more pragmatic approach.


Assuntos
Oftalmologistas , Campos Visuais , Consultores , Humanos , Transtornos da Visão/diagnóstico , Visão Binocular , Testes de Campo Visual
11.
JAMA Ophthalmol ; 139(9): 983-989, 2021 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-34264292

RESUMO

IMPORTANCE: Glaucoma affects more than 75 million people worldwide. Intraocular pressure (IOP)-lowering surgery is an important treatment for this disease. Interest in reducing surgical morbidity has led to the introduction of minimally invasive glaucoma surgeries (MIGS). Understanding the comparative effectiveness and safety of MIGS is necessary for clinicians and patients. OBJECTIVE: To summarize data from randomized clinical trials of MIGS for open-angle glaucoma, which were evaluated in a suite of Cochrane reviews. DATA SOURCES: The Cochrane Database of Systematic Reviews including studies published before June 1, 2021. STUDY SELECTION: Reviews of randomized clinical trials comparing MIGS with cataract extraction alone, other MIGS, traditional glaucoma surgery, laser trabeculoplasty, or medical therapy. DATA EXTRACTION AND SYNTHESIS: Data were extracted according to Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines by one investigator and confirmed by a second. Methodologic rigor was assessed using the AMSTAR 2 appraisal tool and random-effects network meta-analyses were conducted. MAIN OUTCOMES AND MEASURES: The proportion of participants who did not need to use medication to reduce intraocular pressure (IOP) postsurgery (drop-free). Outcomes were analyzed at short-term (<6 months), medium-term (6-18 months), and long-term (>18 months) follow-up. RESULTS: Six eligible Cochrane reviews were identified discussing trabecular bypass with iStent or Hydrus microstents, ab interno trabeculotomy with Trabectome, subconjunctival and supraciliary drainage devices, and endoscopic cyclophotocoagulation. Moderate certainty evidence indicated that adding a Hydrus safely improved the likelihood of drop-free glaucoma control at medium-term (relative risk [RR], 1.6; 95% CI, 1.4 to 1.8) and long-term (RR, 1.6; 95% CI, 1.4 to 1.9) follow-up and conferred 2.0-mm Hg (95% CI, -2.7 to -1.3 mm Hg) greater IOP reduction at long-term follow-up, compared with cataract surgery alone. Adding an iStent also safely improved drop-free disease control compared with cataract surgery alone (RR, 1.4; 95% CI, 1.2 to 1.6), but the short-term IOP-lowering effect of the iStent was not sustained. Addition of a CyPass microstent improved drop-free glaucoma control compared with cataract surgery alone (RR, 1.3; 95% CI, 1.1 to 1.5) but was associated with an increased risk of vraision loss. Network meta-analyses supported the direction and magnitude of these results. CONCLUSIONS AND RELEVANCE: Based on data synthesized in Cochrane reviews, some MIGS may afford patients with glaucoma greater drop-free disease control than cataract surgery alone. Among the products currently available, randomized clinical trial data associate the Hydrus with greater drop-free glaucoma control and IOP lowering than the iStent; however, these effect sizes were small.


Assuntos
Catarata , Glaucoma de Ângulo Aberto , Glaucoma , Trabeculectomia , Catarata/complicações , Glaucoma/cirurgia , Glaucoma de Ângulo Aberto/complicações , Glaucoma de Ângulo Aberto/cirurgia , Humanos , Pressão Intraocular , Metanálise em Rede , Ensaios Clínicos Controlados Aleatórios como Assunto , Revisões Sistemáticas como Assunto , Trabeculectomia/métodos
12.
J Glaucoma ; 29(10): e116-e119, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32826770

RESUMO

Gonioscopy-assisted transluminal trabeculotomy (GATT) is a minimally invasive ab interno procedure, performed with guidance of an illuminating microcatheter device (iTrack). The pathophysiology of raised intraocular pressure (IOP) in uveitic glaucoma is commonly due to increased resistance at the trabecular meshwork-Schlemm canal. By removing this resistance, GATT can potentially control the IOP. In addition, the ab interno approach avoids violating the conjunctiva and reduces the risk of complications including infection, leak, and hypotony. In this series, we discuss 3 uveitic glaucoma cases secondary to juvenile idiopathic arthritis (JIA) that underwent GATT. Case 1 was a 16-year-old phakic female with a preoperative IOP of 25 to 33 mm Hg had 360-degree GATT; her IOP remained stable at 6 to 10 mm Hg over 14 months. Case 2 was a 23-year-old pseudophakic female with a preoperative IOP of 28 to 34 mm Hg had 180-degree GATT; her IOP reduced to 8 mm Hg over 10 months. Case 3 was an 8-year-old aphakic male with a preoperative IOP of 21 to 32 mm Hg had 360-degree GATT; his IOP remained stable at 13 to 15 mm Hg over 21 months. In our limited case series, GATT is very successful in controlling IOP in young uveitic patients with JIA by surgically targeting the underlying pathophysiology.


Assuntos
Artrite Juvenil/complicações , Glaucoma de Ângulo Aberto/cirurgia , Gonioscopia/métodos , Pressão Intraocular/fisiologia , Cirurgia Assistida por Computador/métodos , Trabeculectomia/métodos , Adolescente , Criança , Feminino , Seguimentos , Glaucoma de Ângulo Aberto/etiologia , Glaucoma de Ângulo Aberto/fisiopatologia , Humanos , Masculino , Adulto Jovem
13.
Sci Transl Med ; 12(535)2020 03 18.
Artigo em Inglês | MEDLINE | ID: mdl-32188726

RESUMO

Therapeutic cancer vaccines have effectively induced durable regressions of premalignant oncogenic human papilloma virus type 16 (HPV16)-induced anogenital lesions. However, the treatment of HPV16-induced cancers requires appropriate countermeasures to overcome cancer-induced immune suppression. We previously showed that standard-of-care carboplatin/paclitaxel chemotherapy can reduce abnormally high numbers of immunosuppressive myeloid cells in patients, allowing the development of much stronger therapeutic HPV16 vaccine (ISA101)-induced tumor immunity. We now show the clinical effects of ISA101 vaccination during chemotherapy in 77 patients with advanced, recurrent, or metastatic cervical cancer in a dose assessment study of ISA101. Tumor regressions were observed in 43% of 72 evaluable patients. The depletion of myeloid suppressive cells by carboplatin/paclitaxel was associated with detection of low frequency of spontaneous HPV16-specific immunity in 21 of 62 tested patients. Patients mounted type 1 T cell responses to the vaccine across all doses. The group of patients with higher than median vaccine-induced immune responses lived longer, with a flat tail on the survival curve. This demonstrates that chemoimmunotherapy can be exploited to the benefit of patients with advanced cancer based on a defined mode of action.


Assuntos
Vacinas Anticâncer , Infecções por Papillomavirus , Vacinas contra Papillomavirus , Neoplasias do Colo do Útero , Feminino , Papillomavirus Humano 16 , Humanos , Proteínas E7 de Papillomavirus
14.
J Clin Pharmacol ; 48(1): 43-52, 2008 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-18025524

RESUMO

Peptidic erythropoiesis receptor agonist is a synthetic, PEGylated peptide that can promote red blood cell production upon binding to the erythropoietin receptor. The objective of this study was to characterize the pharmacokinetics and erythropoietic effects of peptidic erythropoiesis receptor agonist in healthy volunteers. Plasma concentrations of peptidic erythropoiesis receptor agonist and pharmacodynamic responses were obtained after single intravenous injections at doses of 0.025, 0.05, and 0.1 mg/kg. Population pharmacokinetic/pharmacodynamic modeling was performed using NONMEM. Peptidic erythropoiesis receptor agonist exhibited nonlinear pharmacokinetics described by a 1-compartment model with parallel elimination by Michaelis-Menten and linear processes. A catenary, life span-based, indirect response model reflecting bone marrow erythroid and blood cells reflected the pharmacodynamics of peptidic erythropoiesis receptor agonist. A modest tolerance and rebound phenomenon in reticulocytes was modeled with negative feedback regulation related to hemoglobin. This pharmacokinetic/pharmacodynamic model well characterized the prolonged disposition, intrinsic pharmacologic parameters, and typical hematological system properties following single doses of peptidic erythropoiesis receptor agonist in normal subjects.


Assuntos
Algoritmos , Hematínicos/farmacocinética , Modelos Biológicos , Receptores da Eritropoetina/agonistas , Administração Oral , Adulto , Ensaios Clínicos Fase I como Assunto , Ensaios Clínicos Controlados como Assunto , Relação Dose-Resposta a Droga , Ensaio de Imunoadsorção Enzimática , Contagem de Eritrócitos , Compostos Ferrosos/administração & dosagem , Compostos Ferrosos/farmacocinética , Hematínicos/administração & dosagem , Hematínicos/sangue , Hemoglobinas/análise , Humanos , Injeções Intravenosas , Masculino , Peptídeos/sangue , Peptídeos/química , Peptídeos/farmacocinética , Polietilenoglicóis/química , Reticulócitos/química , Reticulócitos/citologia , Reticulócitos/efeitos dos fármacos , Fatores de Tempo
15.
Exp Hematol ; 35(8): 1201-8, 2007 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-17662888

RESUMO

OBJECTIVE: To evaluate the potential of Hematide, a PEGylated, synthetic peptide-based erythropoiesis-stimulating agent that is in clinical development for the treatment of anemia associated with chronic kidney disease and cancer, to correct antierythropoietin antibody-associated pure red cell aplasia (PRCA). MATERIALS AND METHODS: The binding of anti-Hematide antibodies (mouse, rabbit, and monkey) to recombinant human erythropoietin (rHuEPO) and of anti-rHuEPO antibodies (mouse, goat, rat, and human) to Hematide were evaluated. An anti-EPO antibody-mediated anemia rat model was developed by subcutaneously administering rHuEPO to rats three times weekly for 4 weeks. Sixty percent of the animals developed PRCA as characterized by severe anemia, reduced reticulocytes, anti-EPO antibodies, and limited bone marrow erythroid precursors. The effect of Hematide administration on the PRCA rats was evaluated. RESULTS: Antibodies to EPO do not cross react with Hematide and, conversely, antibodies to Hematide do not cross react with EPO. Hematide corrected antibody-induced anemia in a rat PRCA model. CONCLUSIONS: The data support the potential of Hematide to correct anti-EPO antibody-associated PRCA in humans. In addition, the data suggest a negligible risk for development of anti-EPO antibody-induced PRCA secondary to Hematide administration.


Assuntos
Anemia/tratamento farmacológico , Eritropoetina/imunologia , Peptídeos/farmacologia , Polietilenoglicóis/farmacologia , Aplasia Pura de Série Vermelha/tratamento farmacológico , Anemia/etiologia , Animais , Anticorpos , Medula Óssea/patologia , Medula Óssea/fisiopatologia , Ensaio de Unidades Formadoras de Colônias , Modelos Animais de Doenças , Eritropoetina/farmacologia , Eritropoetina/uso terapêutico , Humanos , Peptídeos/imunologia , Coelhos , Ratos , Aplasia Pura de Série Vermelha/patologia
17.
JMIR Perioper Med ; 1(2): e11221, 2018 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-33401368

RESUMO

BACKGROUND: The incidence of perioperative visual loss following colorectal surgery in the US is quoted as 1.24 per 10,000. Raised intraocular pressure (IOP) during extreme Trendelenburg position leading to reduced optic nerve perfusion is thought to be a cause. OBJECTIVE: To assess the effect of the degree of Trendelenburg tilt and time spent in Trendelenburg on IOP during laparoscopic colorectal surgery. METHODS: Fifty patients undergoing laparoscopic colorectal surgery were recruited. A Tonopen XL applanation tonometer was used to take IOP measurements hourly during surgery, and each time the operating table was tilted. A correlation coefficient for the degree of Trendelenburg tilt and IOP was calculated for each patient. Group 1 included patients undergoing a right-sided colonic procedure, and Group 2 included all left-sided colonic operations. RESULTS: The mean age of Group 1 participants (n=25) was 69 years (SD 14), and Group 2 (n=25) was 63 years (SD 16; P>.05). The average length of surgery for Group 1 was 142 minutes (SD 48), and Group 2 was 268 minutes (SD 99; P≤.05). The mean maximum degree of Trendelenburg tilt in Group 1 was 10 (SD 7) and Group 2 was 19 (SD 6; P≤.05). The mean IOP increase was 9 mm Hg (SD 5) for Group 1 and 15 mm Hg (SD 5) in Group 2 (P≤.05). An overall correlation coefficient for the degree of Trendelenburg tilt and IOP change (n=48) was .78. CONCLUSIONS: There is a strong correlation between IOP elevation during laparoscopic colorectal surgery and the degree of Trendelenburg tilt. This may be significant for patients undergoing prolonged surgery and especially those with glaucoma.

18.
Acta Ophthalmol ; 96(2): e242-e246, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-28391622

RESUMO

PURPOSE: The SENSIMED Triggerfish® contact lens sensor (CLS) has an embedded micro-sensor that captures spontaneous circumferential changes at the corneoscleral junction and transmits them via an antenna to a device where these measurements are stored. During laparoscopic colorectal surgery, patients are placed in Trendelenburg position which has been shown to increase intraocular pressure (IOP). Laparoscopic colorectal surgery requires both pneumoperitoneum and Trendelenburg positioning; therefore, IOP can vary significantly. We aimed to assess whether circumferential changes in the corneoscleral area can be correlated to IOP changes measured using Tono-pen® XL applanation tonometer during laparoscopic colorectal surgery. METHOD: Patients undergoing laparoscopic colorectal resections were included. On the day of surgery, baseline IOP was taken and the SENSIMED Triggerfish® CLS was then set up in one eye of the patient. During surgery (whilst under general anaesthetic), IOP measurements were taken in the contralateral eye using a Tono-pen® XL applanation tonometer every hour and any time the table was moved to record the fluctuations of IOP during surgery and any association with position change. The timings of these readings were documented. RESULTS: Twenty patients were included in this study (six males, 14 females). Average age was 64.6 years (SD = 16.3). The fluctuation in IOP measured in the reference eye ranged between 6.3 and 46.7 mmHg. The mean correlation coefficient between CLS output measurements and these IOP measurements was r = 0.291 (95% CI). CONCLUSION: Our results showed a weak correlation between the SENSIMED Triggerfish® CLS data output and IOP measurements taken using the Tono-pen® XL applanation tonometer.


Assuntos
Cirurgia Colorretal , Lentes de Contato Hidrofílicas , Pressão Intraocular/fisiologia , Monitorização Intraoperatória/instrumentação , Tonometria Ocular/normas , Adolescente , Adulto , Idoso , Feminino , Humanos , Laparoscopia , Masculino , Pessoa de Meia-Idade , Posicionamento do Paciente , Reprodutibilidade dos Testes
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