How glaucoma patients balance between the advantages and disadvantages of acceptance to the recommended treatment regimen in real-life: Perspectives from a middle-income country.

PURPOSE: Patients with primary open-angle glaucoma (POAG) are required to take long-term treatments with topical medications to halt disease progression. This cross-sectional survey aimed to describe the level of acceptance of Brazilian patients toward the long-term treatment with eyedrops and to find possible correlates of high acceptance. METHODS: POAG patients were recruited from the Glaucoma Service-Santa Casa of Sao Paulo, Sao Paulo, Brazil. Clinical and demographic data were retrieved from participants' electronic records. All patients answered the ACCEPT© questionnaire. This is a generic patient-reported outcome questionnaire specifically developed to assess patients' acceptance of long-term medications and not adherence. Summed scores and those for each domain were calculated to range from 0 to 100 with a higher score indicating greater acceptance. RESULTS: The sample comprised 96 patients with POAG. The mean age was 63.2 ± 8.9 years; 48 were male and 48 female; 55 (57.3%) were white, 36 (37.5%) African-Brazilian, and 5 (5.2%) were of mixed color; most patients (97.9%) had less than high school degree and all had a family income

The association between glaucoma treatment adherence with disease progression and loss to follow-up.

Prospective cohort study from Brazil to evaluate glaucoma treatment adherence using a medication event monitoring system (MEMS) device and correlate with glaucoma progression and loss to follow-up (LTF) after one year of follow up. We included primary open glaucoma (POAG) patients treated with at least one ocular hypotensive eye drop. MEMS devices was used to monitor adherence for 60 days and evaluate the percentage of doses prescribed taken within the 60-day period. We classified patients according to rates of adherence: low adherence (less than 75% from MEMS measurements) and high adherence (more than 75% from MEMS measurements). We applied a questionnaire to investigated self-reported behavior towards treatment behaviors (glaucoma treatment compliance assessment tool, GTCAT). We also correlated rates of treatment adherence with clinical, demographical variables and the occurrence of glaucoma progression or LTF after one year of observation. We included 110 POAG patients and found that 28.18% of them were considered low adherent. We identify several variables associated with poor adherence such as glaucoma progression, LTF, younger age, low educational and income levels, absence of health insurance, years of disease and peak intraocular pressure. Several constructs from the self-reported GTCAT were also correlated with the rates of treatment adherence. To date, this is the first study in Latin America to evaluate glaucoma treatment adherence with MEMS devices and correlate adherence rates with glaucoma progression and LTF. We found a low-adherence rate of 28.18% and several additional risk factors were statistically associated with poor adherence.

Selective Laser Trabeculoplasty as a Substitute for Medications in Patients with Mild-to-moderate Glaucoma in the Brazilian Public Health System.

PRCIS: Selective laser trabeculoplasty can be used as a substitute for medications in patients with mild-to-moderate glaucoma, reducing the cost of eye drop distribution in the Brazilian public health system. PURPOSE: To observe the effectiveness of selective laser trabeculoplasty (SLT) as a substitute for eye drops in patients with open angle glaucoma in the Brazilian Public Health System. MATERIALS AND METHODS: SLT was performed bilaterally after medication washout. This is a prospective interventional study comparing intraocular pressure (IOP) when using eye drops at baseline (post-washout), and at 12-month follow-up after SLT. Medication was added if the target IOP was not achieved, following the Brazilian Public Health System eye drops protocol, based on medication costs. Absolute (without eye drops) and qualified (with eye drops) success were measured with IOP ≤ 21, IOP ≤ 18, IOP ≤ 15 and IOP ≤ 12 mm Hg. Besides IOP evolution, the ability to reduce IOP (in %), and eye drops reduction were evaluated. RESULTS: Ninety-two eyes of 46 patients were included, 70 eyes with mild glaucoma and 22 with moderate glaucoma; the mean number of eye drops was 2.26±1.06 (82.6% were using a prostaglandin analogue), and post-washout IOP of 21.10±5.24 mm Hg. There was relative success at IOP ≤18 mm Hg, where the mild group had greater success than the moderate group (88.1% vs. 71.4%, P =0.824). The average IOP reductions were 23.04% and 25.74% at 6 and 12 months, respectively. The average number of eye drops was 1.02, with 1.1% using a prostaglandin analogue. Furthermore, 68.19% of the patients had a decrease in the quantity of eye drops used. CONCLUSION: SLT is effective in reducing IOP and replacing eye drops in patients in the Brazilian Public Health System. Moreover, there was a significant reduction in the use of prostaglandin analogues.

Perspectives on Adherence to Glaucoma Medical Therapy in Brazilian Patients.

BACKGROUND: Poor adherence to glaucoma medication regimens may be associated with subsequent optic nerve damage and irreversible visual loss. Specific barriers to effective patient adherence in low-middle income countries are not fully recognized and new disease-specific instruments to assess adherence have been developed. OBJECTIVE: The purpose of this cross-sectional study was to evaluate adherence of primary open-angle glaucoma (POAG) patients to treatment in a middle-income country. METHODS: POAG patients were recruited from the Glaucoma Service - Irmandade da Santa Casa de Misericordia de Sao Paulo, Sao Paulo, Brazil. Clinical and demographic data were retrieved from participants' electronic records. All patients answered the Glaucoma Treatment Compliance Assessment Tool (GTCAT). This 27-item questionnaire was designed to evaluate multiple behavioral factors associated with glaucoma medication adherence. RESULTS: The sample comprised 96 patients with POAG. The mean age was 63.2 ± 8.9 years; 48 were male and 48 female; 55 (57.3%) were White, 36 (37.5%) African-Brazilian, and five (5.2 %) were of mixed color. Most patients (97.9%) had less than a high school degree and all had a family income < US$10,000. The GTCAT identified 69 (71.8%) patients who "sometimes forget to use drops," 68 (70.8%) patients who "sometimes fall asleep before dosing time," and 60 (62.5%) patients "whose drops aren't with them at the time to take them"; 82 (85.4%) patients admitted to using "reminders to take medications." Eighty-two (85.4%) patients agreed that "doctor answers my questions," and 77 (80.5%) said "they are happy with their eye doctor." CONCLUSIONS: The GTCAT identified a number of mostly unintentional factors associated with adherence in this cohort of Brazilian patients. The data may impact on how to understand and improve adherence to ocular hypotensive treatment in the Brazilian population.

Selective laser trabeculoplasty versus micropulse laser trabeculoplasty for intraocular pressure control in patients with primary open angle glaucoma: a 12-month retrospective comparative study.

This study was designed to compare the efficacy of selective laser trabeculoplasty (SLT) and micropulse laser trabeculoplasty (MLT) in patients with primary open angle glaucoma (POAG) requiring additional IOP control. In this retrospective, comparative study, we reviewed the charts of POAG patients requiring additional IOP lowering, who underwent either SLT or MLT and were followed for at least one year. We evaluated mean intraocular pressure (IOP), mean IOP reduction from baseline and mean number of glaucoma medications 1, 3, 6 and 12 months after treatment. Success rates (success defined as IOP ≤ 21 mmHg and ≥ 20% reduction from baseline IOP without additional medications, new laser session, or glaucoma surgery) at one year were also compared. A total of 98 POAG patients were included, 52 individuals in the SLT group and 46 in the MLT group. Laser treatment resulted in significant mean IOP reductions from baseline in both groups (SLT = -6.0 ± 3.3 mmHg (24.9%) and MLT = -5.8 ± 2.6 mmHg (23.4%)) (p < 0.001). However, there was no statistically significant difference between the mean IOP reductions in both groups (p = 0.74). At 12 months, the mean number of glaucoma medications was significantly smaller in the SLT group (1.17 + 0.4) when compared to the MLT group (2.21 + 0.2) (p = 0.001). Additionally, after 12 months, success was obtained in 32 (61.5%) SLT cases compared to 27 (58.7%) MLT-treated eyes (p = 1.0). MLT and SLT are both effective in controlling the IOP in POAG patients requiring additional IOP reduction. However, after 12 months, SLT demonstrated a greater efficacy in reducing medication burden when compared to MLT.Trial registration: CEP/CONEP/MS Brazil 40948620.9.0000.5600.

Outcomes of Selective Laser Trabeculoplasty After Prior Incisional Surgery for Open Angle Glaucoma.

PRCIS: This retrospective case series of patients with open angle glaucoma and prior trabeculectomy or tube shunt surgery found that selective laser trabeculoplasty (SLT) resulted in significant intraocular pressure (IOP) reductions in the intermediate follow-up period in select cases. PURPOSE: The purpose of this study was to assess the IOP-lowering effect and tolerability of SLT after prior trabeculectomy or tube shunt surgery. MATERIALS AND METHODS: Open angle glaucoma patients at Wills Eye Hospital who previously underwent incisional glaucoma surgery and subsequently received SLT between 2013 and 2018 were included, along with an age-matched control group. Baseline characteristics, procedural data, and post-SLT data were recorded at 1, 3, 6, 12 months, and most recent visit. The primary success of SLT treatment was defined as IOP reduction of 20% or greater without the use of additional glaucoma medications compared to pre-SLT IOP. Secondary success was defined as IOP reduction ≥20% with the use of additional glaucoma medications compared to pre-SLT IOP. RESULTS: There were 45 eyes in the study group and 45 eyes in the control group. In the study group, IOP decreased from a baseline of 19.5±4.7 mm Hg on 2.2±1.2 medications to 16.7±5.2 mm Hg ( P =0.002) on 2.2±1.1 glaucoma medications ( P =0.57). In the control group, IOP decreased from 19.5±4.2 mm Hg on 2.4±1.0 medications to 16.4±5.2 mm Hg ( P =0.003) on 2.1±1.3 medications ( P =0.36). There was no difference in IOP reduction or change in number of glaucoma medications after SLT at any postoperative visit between the 2 groups ( P ≥0.12 for all). Primary success rates at 12 months were 24.4% for the control group and 26.7% for the prior incisional glaucoma surgery group with no significant difference between the groups ( P =0.92). There were no persistent complications after SLT treatment in either group. CONCLUSION: SLT may effectively lower IOP in patients with open angle glaucoma who have had previous incisional glaucoma surgery and should be considered in select cases.

A multicenter prospective comparative study evaluating cataract surgery and endoscopic cyclophotocoagulation either with or without iStent inject implantation in Brazilian patients with glaucoma.

PURPOSE: Compare 12-month (12 M) safety and efficacy of endoscopic cyclophotocoagulation (ECP) + cataract surgery (Group 1) versus ECP + cataract surgery + iStent inject trabecular micro-bypass implantation (Group 2) in Brazilian patients with open-angle glaucoma (OAG). METHODS: This prospective, multicenter, comparative case series included patients with OAG and cataract who were randomized to receive treatment in Group 1 or Group 2. Outcomes included mean and percent reduction versus preoperative in intraocular pressure (IOP) and number of glaucoma medications; visual acuity; occurrence of adverse events; and rate of secondary surgeries. RESULTS: Preoperatively, Groups 1 and 2 had similar mean IOP (mean ± standard deviation 22.1 ± 3.6 and 22.0 ± 2.5 mmHg, respectively) and mean number of medications (3.3 ± 0.6 and 3.4 ± 0.6 medications, respectively). At all follow-up timepoints through 12 M, both groups achieved significant IOP and medication reductions versus preoperative (IOP p < 0.001 and number of medications p < 0.001 for both groups). At 12 M, IOP reductions were 24.2% (Group 1) and 43.6% (Group 2) (p < 0.001); mean medication reductions were 50.2% and 71.5%, respectively. Mean postoperative IOP and number of medications were higher in Group 1 than Group 2 (IOP p < 0.01 all visits, medication p < 0.01 at 6 M and 12 M). Adverse events were generally mild and infrequent in both groups. CONCLUSION: Both treatment groups (ECP + phacoemulsification, with/without iStent inject implantation) achieved significant and safe reductions in IOP and medications versus preoperative in Brazilian OAG patients. Percent reductions were significantly greater, and mean IOP and medications were significantly lower, in the group receiving iStent inject. CLINICAL TRIAL REGISTRATION (CTR): CAAE project identification #20053019.5.0000.5078. Protocol #3.587.147. Clinical Trial Database of the Federal University of Goiás, Brazil. Registration Date: September 19, 2019.

Trabecular microbypass as replacement therapy in pharmacologically controlled open-angle glaucoma patients.

PURPOSE: To assess the outcomes of the trabecular bypass as replacement therapy for medications in pharmacologically controlled vs. pharmacologically uncontrolled open-angle glaucoma patients. METHODS: This was a retrospective study of eyes treated with first- (iStent) or second-generation (iStent inject) trabecular bypass. Group 1 consisted of eyes with pharmacologically controlled intraocular pressure <18 mmHg and Group 2 consisted of eyes with pharmacologically controlled intraocular pressure ≥18 mmHg. The main outcomes measured were qualified (with or without medications) and unqualified or complete (without medications) success rates at different target intraocular pressures, mean reduction (%) in medication use, and proportion of medication-free eyes. RESULTS: The mean age was 70.4 years in Group 1 (n=105) and 68.1 years in Group 2 (n=65). Qualified success rates for intraocular pressure <18 mmHg, intraocular pressure <15 mmHg, and intraocular pressure <12 mmHg were similar between the groups (Group 1: 96.2%, 88.6%, and 32.4%, respectively; Group 2: 93.8%, 78.5%, and 21.5%, respectively; all p>0.05). Complete success rates were significantly higher in Group 1 than in Group 2: for intraocular pressure <18 mmHg (76.2% vs. 47.7%), intraocular pressure <15 mmHg (73.3% vs. 40.0%), and intraocular pressure <12 mmHg (14.3% vs. 4.6%). The mean reduction in medication use was higher in Group 1 than in Group 2. At the end of follow-up, 79.0% of eyes in Group 1 and 47.7% of eyes in Group 2 became medication-free. CONCLUSIONS: Both groups showed high qualified success rates, but eyes with baseline pharmacologically controlled intraocular pressure <18 mmHg showed higher complete success rates and greater chances of achieving no need for medications.

Laser trabeculoplasty for open-angle glaucoma and ocular hypertension.

BACKGROUND: Open-angle glaucoma (OAG) is an important cause of blindness worldwide. Laser trabeculoplasty, a treatment modality, still does not have a clear position in the treatment sequence. OBJECTIVES: To assess the effects of laser trabeculoplasty for treating OAG and ocular hypertension (OHT) when compared to medication, glaucoma surgery or no intervention. We also wished to compare the effectiveness of different laser trabeculoplasty technologies for treating OAG and OHT. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (which contains the Cochrane Eyes and Vision Trials Register) (2021, Issue 10); Ovid MEDLINE; Ovid Embase; the ISRCTN registry; LILACS, ClinicalTrials.gov and the WHO ICTRP. The date of the search was 28 October 2021. We also contacted researchers in the field. SELECTION CRITERIA: We included randomised controlled trials (RCTs) comparing laser trabeculoplasty with no intervention, with medical treatment, or with surgery in people with OAG or OHT. We also included trials comparing different types of laser trabeculoplasty technologies. DATA COLLECTION AND ANALYSIS: We used standard methods expected by Cochrane. Two authors screened search results and extracted data independently. We considered the following outcomes at 24 months: failure to control intraocular pressure (IOP), failure to stabilise visual field progression, failure to stabilise optic neuropathy progression, adverse effects, quality of life, and costs. We graded the 'certainty' of the evidence using GRADE. MAIN RESULTS: We included 40 studies (5613 eyes of 4028 people) in this review. The majority of the studies were conducted in Europe and in the USA. Most of the studies were at risk of performance and/or detection bias as they were unmasked. None of the studies were judged as having low risk of bias for all domains. We did not identify any studies of laser trabeculoplasty alone versus no intervention. Laser trabeculoplasty versus medication Fourteen studies compared laser trabeculoplasty with medication in either people with primary OAG (7 studies) or primary or secondary OAG (7 studies); five of the 14 studies also included participants with OHT. Six studies used argon laser trabeculoplasty and eight studies used selective laser trabeculoplasty. There was considerable clinical and methodological diversity in these studies leading to statistical heterogeneity in results for the primary outcome "failure to control IOP" at 24 months.  Risk ratios (RRs) ranged from 0.43 in favour of laser trabeculoplasty to 1.87 in favour of medication (5 studies, I2 = 89%). Studies of argon laser compared with medication were more likely to show a beneficial effect compared with studies of selective laser (test for interaction P = 0.0001) but the argon laser studies were older and the medication comparator group in those studies may have been less effective. We considered this to be low-certainty evidence because the trials were at risk of bias (they were not masked) and there was unexplained heterogeneity. There was evidence from two studies (624 eyes) that argon laser treatment was associated with less failure to stabilise visual field progression compared with medication (7% versus 11%, RR 0.70, 95% CI 0.42 to 1.16) at 24 months and one further large recent study of selective laser also reported a reduced risk of failure at 48 months (17% versus 26%) RR 0.65, 95% CI 0.52 to 0.81, 1178 eyes). We judged this outcome as moderate-certainty evidence, downgrading for risk of bias. There was only very low-certainty evidence on optic neuropathy progression. Adverse effects were more commonly seen in the laser trabeculoplasty group including peripheral anterior synechiae (PAS) associated with argon laser (32% versus 26%, RR 11.74, 95% CI 5.94 to 23.22; 624 eyes; 2 RCTs; low-certainty evidence); 5% of participants treated with laser in three studies of selective laser group had early IOP spikes (moderate-certainty evidence). One UK-based study provided moderate-certainty evidence that laser trabeculoplasty was more cost-effective.  Laser trabeculoplasty versus trabeculectomy Three studies compared laser trabeculoplasty with trabeculectomy. All three studies enrolled participants with OAG (primary or secondary) and used argon laser. People receiving laser trabeculoplasty may have a higher risk of uncontrolled IOP at 24 months compared with people receiving trabeculectomy (16% versus 8%, RR 2.12, 95% CI 1.44 to 3.11; 901 eyes; 2 RCTs). We judged this to be low-certainty evidence because of risk of bias (trials were not masked) and there was inconsistency between the two trials (I2 = 68%). There was limited evidence on visual field progression suggesting a higher risk of failure with laser trabeculoplasty. There was no information on optic neuropathy progression, quality of life or costs. PAS formation and IOP spikes were not reported but in one study trabeculectomy was associated with an increased risk of cataract (RR 1.78, 95% CI 1.46 to 2.16) (very low-certainty evidence). AUTHORS' CONCLUSIONS: Laser trabeculoplasty may work better than topical medication in slowing down the progression of open-angle glaucoma (rate of visual field loss) and may be similar to modern eye drops in controlling eye pressure at a lower cost. It is not associated with serious unwanted effects, particularly for the newer types of trabeculoplasty, such as selective laser trabeculoplasty.

Duration of the hypotensive effect of prostaglandin analogues measured with the water drinking test in glaucoma patients.

OBJECTIVE: To measure the magnitude and duration of the hypotensive effect of two prostaglandin analogues in glaucoma patients using the water drinking test (WDT). METHODS: Patients received latanoprost or travoprost every 24 h and then every 48 h. Untreated WDT were performed at 7 am and with treatment 12, 36 and 44 h after the last dose; intraocular pressure (IOP) peak, fluctuation and the difference between peak and isolated IOP measurements at consultation times were calculated. RESULTS: Forty-one eyes of 21 patients with primary open-angle glaucoma were included; 22 eyes received latanoprost, and 19 received travoprost. Mean untreated isolated IOP was 17.20 standard deviation (S.D.) 3.73 and 16.95 S.D. 2.61 mmHg and peak pressure 22.45 S.D. 2.91 and 21.58 S.D. 3.79 mmHg, for the latanoprost and travoprost groups, respectively. With treatment, peak pressure was reduced by 22.64% and 20.29% at 12 h, 18.44% and 14.64% at 36 h and 16.17% and 14.46% at 44 h, respectively. The fluctuation without treatment was 4.36 and 5.11 mmHg, and with treatment at 12 h was reduced to 2.77 and 2.89 mmHg, increasing again at 36 and 44 h. CONCLUSIONS: A hypotensive effect was evident up to 44 h after the last dose of latanoprost and travoprost, similar for the two drugs and decreasing over time. IOP fluctuation was only reduced at 12 h.

Implante de drenagem oftalmológico no tratamento do glaucoma primário de ângulo aberto leve a moderado / Ophthalmic drainage implant in the treatment of mild to moderate open angle primary glaucoma

INTRODUÇÃO: O glaucoma é uma neuropatia ótica degenerativa que evolui com perda do campo visual e cegueira. A pressão intraocular superior a 21 mmHg é estratégia diagnóstica padrão-ouro e o controle do quadro clínico é considerado como fator associado a retardo na progressão da doença. O tratamento usual é realizado por colírios ou cirurgia para casos refratários. O produto em saúde que avaliado neste relatório consiste em procedimento cirúrgico microinvasivo com implante de microstent, que tem como objetivo reduzir a pressão intraocular e controlar a progressão da doença. TECNOLOGIA: iStent inject® Trabecular Micro-Bypass System. PERGUNTA: iStent é seguro, eficaz e custo-efetivo em relação ao tratamento com colírios para adultos com glaucoma primário de ângulo aberto após falha de pelo menos um colírio? EVIDÊNCIAS CIENTÍFICAS: O demandante apresentou dois estudos como evidência, no entanto, após análise do material o parecerista externo considerou que a busca por evidências realizada mostrou incoerência entre a estrutura da pergunta de pesquisa proposta, a elaboração da busca e a estratégia de seleção dos estudos. Assim, nova pergunta de pesquisa e busca na literatura foram feitas, onde apenas um estudo de alto risco de viés foi identificado. De acordo com essa evidência, o efeito do dispositivo foi semelhante ao uso de colírios, com a única vantagem de reduzir o número de aplicações, no entanto, o procedimento apresenta riscos de complicações a serem consideradas. AVALIAÇÃO ECONÔMICA: Foi realizado um estudo de custo-efetividade com método de modelagem de Markov, horizonte temporal lifetime e taxa de desconto anual de 5%. Frente a ausência de claro benefício da tecnologia na evidência clínica, não foi elaborado um novo modelo pelo parecerista externo. O modelo do demandante apresenta o pressuposto que o esquecimento de doses leva a redução do campo visual, o que foi considerado inadequado. No cenário base, foi obtida a razão de custo efetividade incremental (RCEI) de R$ 12.595,26 por ano de vida ganho ajustado pela qualidade (QALY) e no cenário alternativo, R$ 9.139,78/QALY. ANÁLISE DE IMPACTO ORÇAMENTÁRIO: Foi estimado um impacto orçamentário incremental de R$ 8.221.464 no primeiro ano, chegando a R$ 78.417.260 em 5 anos, com o uso do dispositivo. MONITORAMENTO DO HORIZONTE TECNOLÓGICO: Foram encontrados dois depósitos patentários relacionados a implantes oftalmológicos para o tratamento de glaucoma. O primeiro trata-se de um depósito patentário internacional que também possui pedido em âmbito nacional. O referido pedido apresenta um dispositivo ocular implantável e seu respectivo procedimento cirúrgico minimamente invasivo para o seu implante. O segundo é um pedido sem depósito nacional e que se trata de um implante de drenagem destinado ao tratamento cirúrgico de glaucoma primário de ângulo aberto, confeccionado em material acrílico hidrofílico na forma de segmento de anel. CONSIDERAÇÕES: O iStent possui moderada qualidade de evidência para redução da PIO, desfecho substituto para perda da visão em pacientes com GPAA. A magnitude de efeito de redução da PIO é semelhante ao obtido com colírios. O uso de iStent associa-se com o benefício da redução da necessidade do uso de colírios ou redução da quantidade de colírios necessários para a redução da PIO. No entanto, o dispositivo necessita de especialistas treinados para sua implementação. O impacto orçamentário em 5 anos foi estimado em cerca de 78 milhões de reais. Não foi elaborado novo modelo de custo-efetividade pois a efetividade do iStent versus colírios foi considerada semelhante e o custo superior. RECOMENDAÇÃO PRELIMINAR DA CONINTEC: Diante do exposto, a Conitec, em sua 99ª reunião ordinária, realizada no dia 30 de junho de 2021, deliberou que a matéria fosse disponibilizada em consulta pública com recomendação preliminar não favorável à incorporação, no SUS, do implante de drenagem oftalmológico para o tratamento de pacientes com glaucoma de ângulo aberto que falharam ao uso de pelo menos um colírio. Justificou-se esta recomendação com base no alto impacto orçamentário calculado e na fragilidade da evidência científica, que não suportou piora na evolução do tratamento clínico devido a uma menor aderência aos colírios, sugerindo semelhança de efeitos desejáveis entre o implante e os colírios. Além disso, foi observado maior risco de complicações e mínimo benefício clínico no uso do implante, se comparado ao uso de colírios. A matéria foi disponibilizada em consulta pública. CONSULTA PÚBLICA: A Consulta Pública nº 69/2021 foi realizada entre os dias 23/07/2021 e 11/08/2021. Foram recebidas 72 contribuições, sendo 17 pelo formulário para contribuições técnico-científicas e 55 pelo formulário para contribuições sobre experiência ou opinião de pacientes, familiares, amigos ou cuidadores de pacientes, profissionais de saúde ou pessoas interessadas no tema. Assim, o Plenário da Conitec entendeu que houve argumentação suficiente para mudança de entendimento acerca de sua recomendação preliminar. RECOMENDAÇÃO FINAL DA CONITEC: Pelo exposto, o Plenário da Conitec, em sua 101ª Reunião Ordinária, no dia 01 de setembro de 2021, deliberou por unanimidade recomendar a incorporação no SUS do implante de drenagem oftalmológico para o tratamento de pacientes com glaucoma primário de ângulo aberto leve a moderado que falharam ao uso de pelo menos um colírio, conforme Protocolo estabelecido pelo Ministério da Saúde. Assim, foi assinado o Registro de Deliberação nº 659/2021. DECISÃO: Incorporar o implante de drenagem oftalmológico no tratamento do glaucoma primário de ângulo aberto leve a moderado, no âmbito do Sistema Único de Saúde ­ SUS, conforme a Portaria nº 68, publicada no Diário Oficial da União nº 192, seção 1, página 96, em 08 de outubro de 2021.

Topical Bimatoprost Insert for Primary Open-Angle Glaucoma and Ocular Hypertension Treatment - A Phase II Controlled Study.

INTRODUCTION: The most common treatment for Primary Open-Angle Glaucoma (POAG) is the daily use of eye drops. Sustained-release drug delivery systems have been developed to improve patient adherence by achieving prolonged therapeutic drug concentrations in ocular target tissues while limiting systemic exposure. The purpose of this study is to compare the efficacy and safety of bimatoprost inserts with bimatoprost eye drops in patients with POAG and Ocular Hypertension (OH). METHODS: We include OH and POAG patients aged between 40 and 75 years-old. Both OH and POAG patients had intraocular pressure (IOP) greater than 21 and ≤30 mmHg at 9:00 am without glaucoma medication and normal biomicroscopy. Five normal patients with IOP≤14 mmHg constitute the control group. A chitosan-based insert of bimatoprost was placed at the upper conjunctival fornix of the right eye. In the left eye, patients used one drop of LumiganTM daily at 10:00 pm. For statistical analysis, a two-way analysis of variance (ANOVA), Student t-test, and paired t-test is used. RESULTS: Sixteen POAG and 13 OH patients with a mean age of 61 years were assessed. In both eyes, IOP reduction was similar during three weeks of follow-up (19.5±2.2 mmHg and 16.9±3.1 mmHg), insert, and eye drop, respectively; P=0.165). The percentage of IOP reduction in the third week was 30% for insert and 35% for eye drops (P=0.165). No intolerance or discomfort with the insert was reported. Among the research participants, 58% preferred the use of the insert while 25% preferred eye drops, and 17% reported no preference. CONCLUSION: Bimatoprost-loaded inserts showed similar efficacy to daily bimatoprost eye drops during three weeks of follow up, without major side effects. This might suggest a possible change in the daily therapeutic regimen for the treatment of POAG and OH.

New antiglaucomatous agent for the treatment of open angle glaucoma: Polymeric inserts for drug release and in vitro and in vivo study.

A benzamidine derivative from diminazene was tested for a novel activity: treatment of primary open-angle glaucoma. This drug was incorporated into mucoadhesive polymeric inserts prepared using chitosan (Chs) and chondroitin sulfate (CS). Of current interest is the mucoadhesion, which increases the contact time with the ocular surface, resulting in improved bioavailability; also, the inserts are made to act as a prolonged release system. In the present work the inserts were prepared by the solvent casting method using different polymeric proportions (30:70, 50:50, 75:25% w/w Chs:CS and 100% Chs). Thermal analysis and infrared spectroscopy both demonstrated physical dispersion of the active drug. The most promising was the 50:50% Chs:CS which demonstrated that it was not fragile and has an in vitro release profile of up to 180 minutes. In addition, it presented greater adhesion strength in relation to the other formulations. These physicochemical results corroborate the in vivo tests performed. In this sense, we also demonstrated that the treatment with the 50:50% insert can control the intraocular pressure (IOP) for at least 3 weeks and prevents damage to the retinal ganglion cells (RGCs) compared to the placebo insert. Thus, this indicates thus that the new drug is quite viable and promising in glaucoma treatment.

Long-term Results of the PRESERFLO MicroShunt in Patients With Primary Open-angle Glaucoma From a Single-center Nonrandomized Study.

PRECIS: The MicroShunt was implanted in 23 patients with primary open-angle glaucoma (POAG) in a feasibility study. Reductions in intraocular pressure (IOP) and medications were sustained for up to 5 years with no long-term sight-threatening adverse events (AEs). PURPOSE: The purpose of this study was to assess the long-term effectiveness and safety of the PRESERFLO MicroShunt (8.5 mm long, 70 µm lumen surgical device, formerly known as the InnFocus MicroShunt) in POAG. PATIENTS AND METHODS: In a feasibility study (NCT00772330), patients with POAG inadequately controlled on maximum tolerated therapy with IOP ≥18 to ≤40 mm Hg underwent MicroShunt implantation with adjunctive mitomycin C (0.4 mg/mL), alone or in combination with cataract surgery. Years 1 to 3 findings have previously been reported. Endpoints of this extension study included IOP reduction and success at years 4 and 5 (primary), incidence of AEs, medication use, and reoperations. RESULTS: Mean IOP was reduced from 23.8±5.3 mm Hg at baseline to 12.8±5.6 mm Hg (year 4; n=21) and 12.4±6.5 mm Hg (year 5; n=21). Overall success (with/without medication use) was 87.0% (year 4) and 82.6% (year 5). The mean number of medications reduced from 2.4±1.0 at baseline to 0.8±1.3 (year 5). Common (≥5% of patients) AEs included corneal edema (n=4), transient hypotony (n=4), bleb-related complications (n=3), and device touching the iris (n=3). There were 4 reports of serious AEs and 2 reoperations. CONCLUSIONS: In this extension study, sustained reductions in mean IOP and medications were observed up to 5 years post-MicroShunt implantation. There were no reports of long-term sight-threatening AEs and a low rate of postoperative interventions.

Comparative evaluation of Latanoprostene Bunod, Timolol Maleate, and latanoprost Ophthalmic Solutions to assess their safety and efficacy in lowering intraocular pressure for the management of Open-Angle Glaucoma.

OBJECTIVES: Timolol maleate has been reported to be a safer intraocular pressure (IOP) lowering treatment than latanoprost. The United States Food and Drug Administration approved latanoprostene bunod, a nitric oxide-donating prodrug of latanoprost, for lowering IOP. This study compared the safety and efficacy of latanoprost, latanoprostene bunod, and timolol maleate in patients with open-angle glaucoma. METHODS: Patients who received latanoprost eye drops once daily in the evening were included in the latanoprost Ophthalmic Solutions (LP) cohort (n=104). Those who received latanoprostene bunod eye drops once daily in the evening were included in the Latanoprostene Bunod (LB) cohort (n=94). Those who received timolol eye drops twice daily were included in the Timolol Maleate (TM) cohort (n=115). All treatments were administered to the affected eye(s) for 3 months. Informed Consent has been taken from each participant before the trial. RESULTS: At the end of 3 months of treatment, latanoprost, latanoprostene bunod, and timolol were all successful in reducing IOP. The LB cohort had the highest reduction in IOP, compared to the LP and TM cohorts. All treatments had some common adverse ocular effects. CONCLUSION: Latanoprostene bunod was superior to latanoprost and timolol for the treatment of open-angle glaucoma.

[Type IV hypersensitivity to timolol]. / Hipersensibilidad tipo IV por timolol.

BACKGROUND: In recent years, there have been reports of contact dermatitis due to the beta-blockers that are used in the treatment of glaucoma, such as timolol, levubonolol, carteolol, or betaxolol. CASE REPORT: A 37-year-old male patient, who was diagnosed with bilateral primary open-angle glaucoma two years ago, was in therapy with dorzolamide and a topical ß-adrenergic blocker (timolol) in drops twice a day. Months later, he reported conjunctival hyperemia, stinging, and inflammation of both eyelids, followed by erythematous dermatitis, which improved upon treatment discontinuation. The patch test came back negative, but the conjunctival provocation test came back positive 48 hours later. CONCLUSION: Sensitization to the ophthalmic drops that are used to control glaucoma proved to be the mechanism that was causing the clinical picture of the patient. Performing a tolerance test for active anti-glaucoma agents may be helpful in improving tolerance to the medical treatment of some patients, thus, avoiding laser procedures and/or precipitated antiglaucomatous surgeries.

Antecedentes: En los últimos años se han comunicado casos de dermatitis de contacto debido a betabloqueadores utilizados en el tratamiento del glaucoma como el timolol, levubonol, carteolol o betaxolol. Caso clínico: Hombre de 37 años de edad con diagnóstico dos años atrás de glaucoma primario de ángulo abierto bilateral, en terapia con dorzolamida y un agente betabloqueador adrenérgico tópico (timolol) en gotas, dos veces al día. Meses después consultó por hiperemia conjuntival, escozor e inflamación de párpados de ambos ojos seguida de dermatitis eritematosa, que mejoraban al suspender el tratamiento. La prueba del parche resultó negativa, pero la prueba de provocación conjuntival resultó positiva a las 48 horas. Conclusión: La sensibilización a las gotas oftálmicas que se emplean para controlar el glaucoma resultó ser el mecanismo responsable del cuadro clínico de la paciente. La prueba de tolerancia a los principios activos antiglaucomatosos puede resultar de ayuda para mejorar la tolerancia al tratamiento médico de algunos pacientes, con lo que podría evitarse procedimientos con láser o cirugías antiglaucomatosas precipitadas.

Comparative evaluation of Latanoprostene Bunod, Timolol Maleate, and latanoprost Ophthalmic Solutions to assess their safety and efficacy in lowering intraocular pressure for the management of Open-Angle Glaucoma

OBJECTIVES: Timolol maleate has been reported to be a safer intraocular pressure (IOP) lowering treatment than latanoprost. The United States Food and Drug Administration approved latanoprostene bunod, a nitric oxide-donating prodrug of latanoprost, for lowering IOP. This study compared the safety and efficacy of latanoprost, latanoprostene bunod, and timolol maleate in patients with open-angle glaucoma. METHODS: Patients who received latanoprost eye drops once daily in the evening were included in the latanoprost Ophthalmic Solutions (LP) cohort (n=104). Those who received latanoprostene bunod eye drops once daily in the evening were included in the Latanoprostene Bunod (LB) cohort (n=94). Those who received timolol eye drops twice daily were included in the Timolol Maleate (TM) cohort (n=115). All treatments were administered to the affected eye(s) for 3 months. Informed Consent has been taken from each participant before the trial. RESULTS: At the end of 3 months of treatment, latanoprost, latanoprostene bunod, and timolol were all successful in reducing IOP. The LB cohort had the highest reduction in IOP, compared to the LP and TM cohorts. All treatments had some common adverse ocular effects. CONCLUSION: Latanoprostene bunod was superior to latanoprost and timolol for the treatment of open-angle glaucoma.

Avaliação econômica do glaucoma primário de ângulo aberto / Economic evaluation of primary open-angle glaucoma

Resumo Objetivo: Avaliar a relação custo-utilidade do tratamento inicial com laser ou medicamentos do glaucoma primário de ângulo aberto (GPAA) no Brasil, considerando de um lado os custos totais e de outro lado o impacto na qualidade de vida dos pacientes. Métodos: O estudo foi realizado com base em um modelo de Markov, onde uma coorte teórica de portadores de GPAA em estágio inicial foi gerada. Os parâmetros usados no modelo foram obtidos na literatura e incluíram: custos médicos diretos (consultas, exames, tratamento); custos não médicos diretos (gasto com hospedagem, transporte, alimentação, acompanhante); custos indiretos (relacionados à incapacidade para o trabalho); valores de utilidade (qualidade de vida medida em QALY - quality-adjusted life year); e probabilidade de transição entre os estágios de saúde. Três estratégias de tratamento foram testadas no modelo: (1) sem tratamento; (2) tratamento inicial com colírios; (3) tratamento inicial com trabeculoplastia a laser. A medida de desfecho foi a razão de custo-utilidade incremental (RCUI). A robustez do modelo foi testada através de análise de sensibilidade. Resultados: As estratégias (2) e (3) de tratamento inicial do GPAA geraram ganhos em qualidade de vida em relação à (1) no Brasil. Iniciar o tratamento com laser gerou ganho médio de 1 QALY, enquanto que com medicamentos propiciou um ganho de 2 QALYs em média. Dentre as três estratégias testadas, a estratégia (2) foi a custo-efetiva e foi dominante sobre as demais, pois foi ao mesmo tempo a mais barata e a mais efetiva. Conclusão: Tanto a trabeculoplastia a laser quanto os medicamentos como tratamentos primários do GPAA inicial geraram ganhos significativos de qualidade de vida. A estratégia de se iniciar o tratamento com medicações foi custo-efetiva, quando se considera os custos totais. A alternativa de tratamento inicial através de trabeculoplastia a laser não foi custo-efetiva.

Abstract Objective: To evaluate the cost-utility relation of the initial treatment with laser or primary open-angle glaucoma medications (PLA) in Brazil, considering on the one hand the total costs and on the other side the impact on patients' quality of life. Methods: The study was performed based on a Markov model, where a theoretical cohort of early-stage GPAA carriers was generated. The parameters used in the model were obtained in the literature and included: direct medical costs (consultations, examinations, treatment); direct non-medical costs (accommodation, transportation, meals, companions); indirect costs (related to incapacity for work); utility values (quality of life measured in QALY - quality-adjusted life year); and probability of transition between stages of health. Three treatment strategies were tested in the model: (1) without treatment; (2) initial treatment with eye drops; (3) initial treatment with laser trabeculoplasty. The measure of outcome was the incremental cost-utility ratio (RCUI). The robustness of the model was tested through sensitivity analysis. Results: The strategies (2) and (3) of the initial treatment of POAG generated gains in quality of life in relation to (1) in Brazil. Initiating the laser treatment generated an average gain of 1 QALY, whereas with medication it gave a gain of 2 QALYs on average. Among the three strategies tested, strategy (2) was cost-effective and was dominant over the other strategies, since it was at the same time the cheapest and the most effective strategy. Conclusion: Both laser trabeculoplasty and medications as primary treatments of early-stage POAG have generated significant gains in quality of life. The strategy of starting treatment with medications was cost-effective, whereas laser trabeculoplasty strategy was not cost-effective, when non-medical costs (direct and indirect) are included.

Eficácia do travoprosta 0, 004% na redução da pressão intraocular em pacientes com glaucoma / Travoprosta 0, 004% efficacy in intraocular pressure in patients with glaucoma

Resumo Objetivo: avaliar a eficácia do colírio TRAVAMED® (travoprosta 0,004%) (Ofta, Brasil) na redução da pressão intraocular (PIO), em pacientes com glaucoma primário de ângulo aberto (GPAA) ou hipertensão ocular (HO), bem como avaliar os efeitos colaterais decorrentes do uso da droga. Métodos: estudo randomizado, controlado, com 70 olhos de 38 pacientes acima de 18 anos de idade, com diagnóstico de GPAA ou HO. Todos os pacientes receberam o colírio TRAVAMED® como primeira droga a ser introduzida no tratamento, tendo sido utilizada uma gota uma vez ao dia (à noite), e 30 dias após foram submetidos à tonometria de aplanação (Goldmann) para mensuração da PIO, com o mesmo examinador, no mesmo tonômetro e nos mesmos horários. Resultados: A média de redução da PIO após 30 dias de uso do TRAVAMED® foi de 7,46 mmHg. Em relação aos efeitos colaterais, 15,71% (11) dos olhos apresentaram hiperemia conjuntival, 8,57% (6) apresentaram dor, 8,57% (6) apresentaram ardência, 2,86% (2) apresentaram embaçamento visual e em 1,56% (1) dos olhos não houve queda significativa da PIO. Conclusão: A medicação TRAVAMED® foi eficiente na redução da PIO após 30 dias de uso contínuo, na dose de 1x/dia. Acerca dos efeitos colaterais, os mais observados foram hiperemia ocular (15,71%), dor (8,57%) e ardência (8,57%), porém estudos com maior tempo de seguimento se fazem necessários.

Abstract Objective: to evaluate how much decreases intraocular pressure (IOP) with TRAVAMED® (travoprost 0,004%) (Germed, Brazil) in patients with primary open angle glaucoma (POAG) and ocular hypertension (OH) and possible side effects. Methods: controlled and randomized study, it was evaluated 70 eyes of 38 patients with age of 18 years old or more diagnosed with POAG and OH. All the patients had TRAVAMED® as first drop for treatment used once daily (at night) and 30 days later they had IOP measured by Goldmann tonometry, with the same examiner in the same tonometer at the same times. Results: the mean decrease in IOP was 7,46 mmHg after 30 days using the drops. 15.71% (11) of eyes had conjunctival redness, 8.57% (6) had pain, 8.57% (6) had burning, 2.86% (2) had blurring vision and 1.56% (1) of the eyes there wasn't a significant reduction in IOP. Conclusion: TRAVAMED® was efficient when evaluating IOP decrease. The most correlated side effects were conjunctival redness (15.71%), pain (8.57%) and burning (8.57%), but studies with longer follow-up are needed.

Evaluation of Ocular Surface Disease in Patients With Glaucoma: Clinical Parameters, Self-report Assessment, and Keratograph Analysis.

PURPOSE: To assess ocular surface disease (OSD) in glaucoma using clinical parameters, self-report assessment, and keratograph analysis. METHODS: A total of 30 glaucoma patients and 27 subjects with cataracts (control group) were enrolled in the study. Only glaucoma patients who were using at least 1 topical intraocular pressure-lowering medication were included. An ophthalmological examination was performed, including tear break-up time (BUT), assessment of conjunctival hyperemia and keratitis, and completion of the Ocular Surface Disease Index (OSDI) questionnaire. All the patients underwent keratograph analysis including noninvasive BUT, meibography, tear meniscus height, and redness scale. Quality of life was also assessed in all the patients using National Eye Institute Visual Function Questionnaire (NEI VFQ)-25. The comparison of OSD between the 2 groups was assessed. RESULTS: There was a significant difference in OSD: keratitis and conjunctival hyperemia were worse in the glaucoma group (P=0.009 and 0.008, respectively). The glaucoma group had significantly worse scores on the OSDI questionnaire (32.53±20.75 vs. 20.42±18.77; P=0.007). For the keratograph assessment, the glaucoma group had significantly smaller tear meniscus height (0.22±0.08 vs. 0.24±0.04, respectively; P=0.041); worse bulbar redness (2.06±0.67 vs. 1.70±0.45, respectively; P=0.021); higher meibography grades (2.34±1.01 vs. 1.52±0.64, respectively; P=0.001); and worse noninvasive keratograph tear BUT (5.45±4.16 vs. 8.40±5.65, respectively; P=0.023). Patients with glaucoma had a worse quality of life (60.73±18.25 vs. 76.62±8.03, respectively; P=0.039). CONCLUSIONS: Our findings not only confirm the high prevalence of clinical findings of OSD in glaucoma patients but also reveal new objective parameters measured by keratograph analysis.