Comparison among adjuvant treatments for primary pterygium: a network meta-analysis.

PURPOSE: Pterygium is a frequent ocular disease, where the major challenge is the high level of recurrence after its surgical removal. We performed a network meta-analysis to identify, among several adjuvant treatments for primary pterygium, which is the best to prevent recurrence. METHODS: A search was conducted using PubMed, Scientific Electronic Library Online, Latin American and Caribbean Centre on Health Sciences and Cochrane Eyes and Vision Group Trials Register between 1993 and 2015 for randomisedclinical trials (RCTs) comparing adjuvant treatments following primary pterygium surgery. RESULTS: 24 RCTs that studied 1815 eyes of 1668 patients were included and allowed direct and indirect comparison among 14 interventions through network meta-analysis. The rank from the best to worse treatment to prevent recurrence is: conjunctival autograft + ciclosporin 0.05% eye drops, bare sclera + intraoperativemitomycin C (MMC) <0.02%, bare sclera + beta therapy (2500 cGy single dose), conjunctival autograft + beta therapy (1000 cGy single dose), bare sclera + MMC 0.02% eye drops, conjunctival autograft, bare sclera + intraoperative MMC >0.02%, bare sclera + ciclosporin 0.05% eye drops, bare sclera + intraoperative 5-fluorouracil 5%, amniotic membrane transplantation, bare sclera + intraoperative MMC 0.02%, conjunctival autograft + bevacizumab 0.05% eye drops, bare sclera + bevacizumab 0.05% eye drops and bare sclera alone. CONCLUSION: The best adjuvant treatment to prevent recurrence after primary pterygium surgery is the association of conjunctival autograft and ciclosporin 0.05% eye drops. Bare sclera technique alone should be discontinued since it is associated with high recurrence rates.

Dry eye disease treatment: a systematic review of published trials and a critical appraisal of therapeutic strategies.

Dry eye disease (DED) treatment is an area of increasing complexity, with the emergence of several new treatment agents in recent years. Evaluation of the efficacy of these agents is limited by heterogeneity in outcomes definition and the small number of comparative studies. We provide a systematic review of clinical trials (CTs) related to DED treatment and a critical appraisal of CT public databases. CT reports obtained from eight databases were reviewed, as well as public free-access electronic databases for CT registration. Data evaluation was based on endpoints such as symptoms, Schirmer test, ocular surface staining scores, recruitment of patients, type and efficacy of the drug, and the design and site of performance of the study. Forty-nine CTs were evaluated involving 5,189 patients receiving DED treatment. Heterogeneity in study design prevented meta-analysis from yielding meaningful results, and a descriptive analysis of these studies was conducted. The most frequent categories of drugs for DED in these studies were artificial tears, followed by anti-inflammatory drugs and secretagogues. Although 116 studies have been completed, according to the registration database for clinical trials, only 17 of them (15.5%) were published. Out of 185 registered CTs related to DED, 72% were performed in the USA. The pharmaceutical industry sponsored 78% of them. The identification of effective DED treatment strategies is hindered by the lack of an accepted set of definitive criteria for evaluating disease severity.

Radiation therapy for Graves' ophthalmopathy: a systematic review and meta-analysis of randomized controlled trials / Radioterapia para oftalmopatia de Graves: uma revisão sistemática e meta-análise de ensaios clínicos randomizados e controlados

PURPOSE: To evaluate the efficacy of radiotherapy (RT) with total dose of 20 Gy (RT 20 Gy) in the treatment of Graves' ophthalmopathy. METHODS: A systematic review and meta-analysis of randomized controlled trials was performed comparing RT 20 Gy with or without glucocorticoid to clinical treatments for Graves' ophthalmopathy. The MEDLINE, EMBASE, Cochrane Library databases and recent relevant journals were searched. Relevant reports were reviewed by two reviewers. Response to radiotherapy was defined as clinical success according to each trial. We also evaluated the quality of life and whether RT to produce fewer side effects than other treatments. RESULTS: A total of 8 randomized controlled trials (439 patients) were identified. In the subgroup analysis, the overall response to treatment rates was better for: RT 20 Gy plus glucocorticoid vs glucocorticoids alone, OR=17.5 (CI95% 1.85-250, p=0.04), RT 20 Gy vs sham RT, OR= 3.15 (CI95%1.59-6.23, p=0.003) and RT 20Gy plus intravenous glucocorticoid vs RT 20Gy plus oral glucocorticoid, OR=4.15(CI95% 1.34-12.87, p=0.01). There were no differences between RT 20 Gy versus other fractionations and RT 20 Gy versus glucocorticoid alone. RT 20 Gy with or without glucocorticoids showed an improvement in diplopia grade, visual acuity, optic neuropathy, lid width, proptosis and ocular motility. No difference was seen for costs, intraocular pressure and quality of life. CONCLUSION: Our data have shown that RT 20 Gy should be offered as a valid therapeutic option to patients with moderate to severe ophthalmopathy. The effectiveness of orbital radiotherapy can be increased by the synergistic interaction with glucocorticoids. Moreover, RT 20 Gy is useful to improve a lot of ocular symptoms, excluding intraocular pressure, without any difference in quality of life and costs.

OBJETIVO: Avaliar a eficácia da radioterapia (RT) com dose total de 20 Gy (RT 20 Gy) no tratamento da oftalmopatia de Graves. MÉTODOS: Uma revisão sistemática e meta-análise de ensaios clínicos randomizados foram realizadas comparando RT 20 Gy, com ou sem glicocorticoides a tratamentos clinicos para a oftalmopatia de Graves. O MEDLINE, EMBASE, bases de dados da Biblioteca Cochrane e recentes de revistas relevantes foram pesquisados. Relatórios relevantes foram revisados por dois revisores. A resposta à radioterapia foi definida através do sucesso clinico de acordo a cada ensaio clínico. Nós também avaliamos a qualidade de vida e se a radioterapia produzia menos efeitos colaterais comparados a outras intervenções. RESULTADOS: Um total de 8 ensaios clínicos randomizados (439 pacientes) foram identificados. Na análise de subgrupo, a resposta global para as taxas de tratamento foi melhor para: RT 20 Gy além de glicocorticoides vs glicocorticoides sozinhos, OR=17,5 (IC95% 1,85-250, p=0,04), RT 20 Gy vs sham RT, OR=3,15 (IC95% 1,59-6,23, p=0,003) e RT 20 Gy além de glicocorticoides por via intravenosa RT 20 Gy além de glicocorticoides orais, OR=4,15 (IC95% 1,34-12,87, p=0,01). Não houve diferenças entre RT 20 Gy contra outros fracionamentos e 20 Gy RT contra glicocorticoides sozinhos. RT 20 Gy, com ou sem glicocorticoides mostraram uma melhoria no grau de diplopia, acuidade visual, neuropatia óptica, abertura palpebral, proptose e da motilidade ocular. Não foi observada diferença para os custos, a pressão intraocular e a qualidade de vida. CONCLUSÃO: Nossos dados mostraram que 20 Gy RT deve ser oferecida como uma opção terapêutica válida para pacientes com moderada a severa oftalmopatia de Graves. A eficácia da radioterapia orbital pode ser aumentada pela interação sinérgica com os glicocorticoides. Além disso, RT 20 Gy é útil para melhorar vários sintomas oculares, excluindo a pressão intraocular, sem qualquer diferença de qualidade de vida.

Conjunctival autograft alone or combined with adjuvant beta-radiation? A randomized clinical trial.

PURPOSE: To evaluate the effectiveness and safety of postoperative low single-dose of beta-irradiation (ß-RT) in pterygium comparing conjunctival autograft (CAG) surgery with CAG plus adjuvant ß-RT in a randomized clinical trial. METHODS: This trial was designed as a prospective, randomized, single-center study. Surgery was performed in all cases according to the CAG technique. One hundred and eight pterygia were postoperatively randomized to CAG + ß-RT or CAG alone. In the case of ß-RT, a (90) Sr eye applicator was used to deliver 10 Gy to the sclera surface at a dose rate of between 200 and 250 cGy/min. After treatment, both an ophthalmologist and a radiation oncologist performed the follow-up examinations. The accumulated data were analyzed using a group sequential test. RESULTS: Between February 2008 and September 2008, 116 eyes with primary pterygium were operated on according to the trial protocol. Adjuvant treatment was performed within 24 h postoperatively. Eight patients were lost to follow-up, resulting in 108 patients who could be analyzed. At a mean follow-up of 18 months (range, 8-33), in the 54 eyes randomized to receive CAG + ß-RT, 5 relapses occurred compared with 12 recurrences in the 54 eyes in CAG, for a crude control rate of 90.8 % vs. 78%; p = 0.032, respectively. The treatment complications as hyperemia, total dehiscence of the autograft and dellen were significantly more frequent in the CAG (p < 0.05). The arm of ß-RT resulted in better cosmetic results and improves of symptoms than CAG. CONCLUSIONS: A low single-dose of ß-RT of 10 Gy after CAG surgery was a simple, effective, and safe treatment that reduced the risk of primary pterygium recurrence, improved symptoms after surgery, resulting in a better cosmetic effect than only CAG.

Low or high fractionation dose ß-radiotherapy for pterygium? A randomized clinical trial.

PURPOSE: Postoperative adjuvant treatment using ß-radiotherapy (RT) is a proven technique for reducing the recurrence of pterygium. A randomized trial was conducted to determine whether a low fractionation dose of 2 Gy within 10 fractions would provide local control similar to that after a high fractionation dose of 5 Gy within 7 fractions for surgically resected pterygium. METHODS: A randomized trial was conducted in 200 patients (216 pterygia) between February 2006 and July 2007. Only patients with fresh pterygium resected using a bare sclera method and given RT within 3 days were included. Postoperative RT was delivered using a strontium-90 eye applicator. The pterygia were randomly treated using either 5 Gy within 7 fractions (Group 1) or 2 Gy within 10 fractions (Group 2). The local control rate was calculated from the date of surgery. RESULTS: Of the 216 pterygia included, 112 were allocated to Group 1 and 104 to Group 2. The 3-year local control rate for Groups 1 and 2 was 93.8% and 92.3%, respectively (p = .616). A statistically significant difference for cosmetic effect (p = .034), photophobia (p = .02), irritation (p = .001), and scleromalacia (p = .017) was noted in favor of Group 2. CONCLUSIONS: No better local control rate for postoperative pterygium was obtained using high-dose fractionation vs. low-dose fractionation. However, a low-dose fractionation schedule produced better cosmetic effects and resulted in fewer symptoms than high-dose fractionation. Moreover, pterygia can be safely treated in terms of local recurrence using RT schedules with a biologic effective dose of 24-52.5 Gy(10.).

Radiation therapy for Graves' ophthalmopathy: a systematic review and meta-analysis of randomized controlled trials.

PURPOSE: To evaluate the efficacy of radiotherapy (RT) with total dose of 20 Gy (RT 20 Gy) in the treatment of Graves' ophthalmopathy. METHODS: A systematic review and meta-analysis of randomized controlled trials was performed comparing RT 20 Gy with or without glucocorticoid to clinical treatments for Graves' ophthalmopathy. The MEDLINE, EMBASE, Cochrane Library databases and recent relevant journals were searched. Relevant reports were reviewed by two reviewers. Response to radiotherapy was defined as clinical success according to each trial. We also evaluated the quality of life and whether RT to produce fewer side effects than other treatments. RESULTS: A total of 8 randomized controlled trials (439 patients) were identified. In the subgroup analysis, the overall response to treatment rates was better for: RT 20 Gy plus glucocorticoid vs glucocorticoids alone, OR=17.5 (CI95% 1.85-250, p=0.04), RT 20 Gy vs sham RT, OR= 3.15 (CI95%1.59-6.23, p=0.003) and RT 20 Gy plus intravenous glucocorticoid vs RT 20Gy plus oral glucocorticoid, OR=4.15(CI95% 1.34-12.87, p=0.01). There were no differences between RT 20 Gy versus other fractionations and RT 20 Gy versus glucocorticoid alone. RT 20 Gy with or without glucocorticoids showed an improvement in diplopia grade, visual acuity, optic neuropathy, lid width, proptosis and ocular motility. No difference was seen for costs, intraocular pressure and quality of life. CONCLUSION: Our data have shown that RT 20 Gy should be offered as a valid therapeutic option to patients with moderate to severe ophthalmopathy. The effectiveness of orbital radiotherapy can be increased by the synergistic interaction with glucocorticoids. Moreover, RT 20 Gy is useful to improve a lot of ocular symptoms, excluding intraocular pressure, without any difference in quality of life and costs.

[Dry eye: etiopathogenesis and treatment]. / Olho seco: etiopatogenia e tratamento.

Dry eye is a multifactorial disease of tears and ocular surface that causes discomfort, visual disturbance and tear film instability. It is a common disorder that affects specially adults and women and can cause quality of life impairment comparable to migraine, shortness of breath and chronic renal insufficiency, depending on its symptoms or complications. New concepts regarding physiopathology, classification and treatment have been presented and should be known by ophthalmologists because of their relevance on day-by-day application. There are about 100 different medications currently in use for dry eye besides other methods of treatment, so it is necessary to establish what is really safe and effective for dry eye. This paper presents a review about Dry Eye Syndrome etiopathogenesis and treatment.

Olho seco: etiopatogenia e tratamento / Dry eye: etiopathogenesis and treatment

Olho seco é uma doença multifatorial das lágrimas e da superfície ocular que resulta em desconforto, distúrbios visuais e instabilidade do filme lacrimal. É uma desordem comum que afeta principalmente adultos e mulheres e que pode causar impacto na qualidade de vida comparável a enxaqueca, dispnéia e insuficiência renal crônica, dependendo dos sintomas ou complicações que a acompanham. Novos conceitos com relação à fisiopatologia, classificação e tratamento têm sido apresentados e devem ser conhecidos pelos oftalmologistas pela sua larga aplicação no dia-a-dia. Estima-se que haja 100 medicações diferentes em uso para olho seco atualmente, além de outros métodos de tratamento, sendo necessário se estabelecer o que é realmente seguro e eficaz. Este texto faz uma revisão sobre etiopatogênese e tratamento da síndrome do Olho Seco.

Dry eye is a multifactorial disease of tears and ocular surface that causes discomfort, visual disturbance and tear film instability. It is a common disorder that affects specially adults and women and can cause quality of life impairment comparable to migraine, shortness of breath and chronic renal insufficiency, depending on its symptoms or complications. New concepts regarding physiopathology, classification and treatment have been presented and should be known by ophthalmologists because of their relevance on day-by-day application. There are about 100 different medications currently in use for dry eye besides other methods of treatment, so it is necessary to establish what is really safe and effective for dry eye. This paper presents a review about Dry Eye Syndrome etiopathogenesis and treatment.

Whole brain radiotherapy with radiosensitizer for brain metastases.

PURPOSE: To study the efficacy of whole brain radiotherapy (WBRT) with radiosensitizer in comparison with WBRT alone for patients with brain metastases in terms of overall survival, disease progression, response to treatment and adverse effects of treatment. METHODS: A meta-analysis of randomized controlled trials (RCT) was performed in order to compare WBRT with radiosensitizer for brain metastases and WBRT alone. The MEDLINE, EMBASE, LILACS, and Cochrane Library databases, in addition to Trial registers, bibliographic databases, and recent issues of relevant journals were researched. Significant reports were reviewed by two reviewers independently. RESULTS: A total of 8 RCTs, yielding 2317 patients were analyzed. Pooled results from this 8 RCTs of WBRT with radiosensitizer have not shown a meaningful improvement on overall survival compared to WBRT alone OR = 1.03 (95% CI0.84-1.25, p = 0.77). Also, there was no difference in local brain tumor response OR = 0.8(95% CI 0.5 - 1.03) and brain tumor progression (OR = 1.11, 95% CI 0.9 - 1.3) when the two arms were compared. CONCLUSION: Our data show that WBRT with the following radiosentizers (ionidamine, metronidazole, misonodazole, motexafin gadolinium, BUdr, efaproxiral, thalidomide), have not improved significatively the overall survival, local control and tumor response compared to WBRT alone for brain metastases. However, 2 of them, motexafin- gadolinium and efaproxiral have been shown in recent publications (lung and breast) to have positive action in lung and breast carcinoma brain metastases in association with WBRT.

[Assessment of visual acuity evaluation performed by teachers of the "Eye in eye" program in Marília-SP, Brazil]. / Qualidade da avaliação da acuidade visual realizada pelos professores do programa " Olho no olho" da cidade de Marília, SP.

PURPOSE: To assess quality and cut-off point (VA <0.7) of the examinations performed by teachers to detect reduced visual acuity (VA) in schoolchildren participants of the project called "Eye in eye " in Marilia-SP, Brazil. METHODS: Visual acuity measurements were performed by trained teachers using Snellen's chart. The children with VA <0.7 in one of the eyes were referred to an ophthalmic examination. The ophthalmic examination was considered gold standard to assess quality and cut-off point of the examinations performed by teachers. VA test was performed in 604 schoolchildren of state public schools (1,208 eyes). Analyses were based on examined eyes. We calculated sensitivity (S), specificity (E), positive predictive value (PPV), negative predictive value (NPV) and likelihood rate (LR). We compared the means obtained by the teachers' examinations to means of the ophthalmologist's examinations. ROC curve was produced to evaluate whether VA lower than 0.7 is the best value for referral to an ophthalmic examination. RESULTS: VA means obtained by teachers and ophthalmologic examinations were 0.70 +/- 0.16 and 0.88 +/- 0.2 respectively. The difference between teachers' and ophthalmologists' examinations was 0.18 (p<0.0001). S, E, PPV, NPV and LR were: 82%, 40%, 27%, 89% and 1.37, respectively. False positive and negative rates were 59.5% and 18%. ROC curve evidenced that visual acuity of 0.7 was the best cut-off point to refer schoolchildren to an ophthalmic exam. CONCLUSIONS: We demonstrated the importance of the teachers' participation in improved schoolchildren ocular health. The examination performed by teachers obtained a satisfactory S with low E, NPV and high values of false positive results. The best cut-off point to refer schoolchildren to an ophthalmic examination was VA of 0.7.

Qualidade da avaliação da acuidade visual realizada pelos professores do programa " Olho no olho" da cidade de Marília, SP / Assessment of visual acuity evaluation performed by teachers of the \"Eye in eye\" program in Marília-SP, Brazil

OBJETIVOS: Avaliar a qualidade e o ponto de corte (AV <0,7) da acuidade visual verificada pelos professores, nos escolares da rede municipal de Marília participantes do programa "Olho no olho". MÉTODOS: Estudo transversal em 604 escolares (1.208 olhos), pertencentes às escolas municipais de Marília, SP, realizado através do exame feito pelos professores treinados para o programa comparando-o com o exame realizado pelos oftalmologistas, assumindo estes como o padrão-ouro para comparação. A análise foi feita por olhos examinados. Calculamos a sensibilidade (S), especificidade (E), valor preditivo positivo (VPP), valor preditivo negativo (VPN) e razão de verossimilhança (RV). Comparamos as médias das AV encontradas pelos professores com as dos oftalmologistas e uma curva ROC (Receiver Operating Characteristic Curve) foi gerada para avaliar se AV <0,7 foi o melhor valor para encaminhamento. RESULTADOS: A média da AV verificada pelos professores foi de 0,70 +/- 0,16 e a dos oftalmologistas foi de 0,88 +/- 0,2 com uma diferença entre as médias de 0,18 (p<0,0001). A S, E, VPP, VPN e RVP foram de: 82 por cento, 40 por cento, 27 por cento, 89 por cento e 1,37, respectivamente. As taxas de falso positivo e negativo foram de 59,5 por cento e 18 por cento, respectivamente. Na curva ROC AV <0,7 foi o melhor ponto para encaminhamento. CONCLUSÕES: Evidenciamos a importância da participação dos professores na melhoria da saúde ocular escolar. O teste realizado pelos professores teve satisfatória S, com baixa E, VPN e valores elevados de falsos positivos. Nossos dados confirmam que o melhor valor de corte para encaminhamento foi o valor de AV < 0,7.

PURPOSE: To assess quality and cut-off point (VA <0.7) of the examinations performed by teachers to detect reduced visual acuity (VA) in schoolchildren participants of the project called "Eye in eye " in Marilia-SP, Brazil. METHODS: Visual acuity measurements were performed by trained teachers using Snellen's chart. The children with VA <0.7 in one of the eyes were referred to an ophthalmic examination. The ophthalmic examination was considered gold standard to assess quality and cut-off point of the examinations performed by teachers. VA test was performed in 604 schoolchildren of state public schools (1,208 eyes). Analyses were based on examined eyes. We calculated sensitivity (S), specificity (E), positive predictive value (PPV), negative predictive value (NPV) and likelihood rate (LR). We compared the means obtained by the teachers' examinations to means of the ophthalmologist's examinations. ROC curve was produced to evaluate whether VA lower than 0.7 is the best value for referral to an ophthalmic examination. RESULTS: VA means obtained by teachers and ophthalmologic examinations were 0.70 ± 0.16 and 0.88 ± 0.2 respectively. The difference between teachers' and ophthalmologists' examinations was 0.18 (p<0.0001). S, E, PPV, NPV e LR were: 82 percent, 40 percent, 27 percent, 89 percent and 1.37, respectively. False positive and negative rates were 59.5 percent and 18 percent. ROC curve evidenced that visual acuity of 0.7 was the best cut-off point to refer schoolchildren to an ophthalmic exam. CONCLUSIONS: We demonstrated the importance of the teachers' participation in improved schoolchildren ocular health. The examination performed by teachers obtained a satisfactory S with low E, NPV and high values of false positive results. The best cut-off point to refer schoolchildren to an ophthalmic examination was VA of 0.7.

Long-term results and prognostic factors of fractionated strontium-90 eye applicator for pterygium.

PURPOSE: To evaluate the long-term safety, effectiveness, and prognostic factors of fractionated postoperative beta-irradiation. METHODS AND MATERIALS: Between 1993 and 2005, 623 patients with 737 pterygium lesions were treated with a strontium-90 eye applicator after surgical excision. The median follow-up period was 60 months (range, 6.7-139.5). Of the 737 lesions, 644 were primary and 93 were recurrences after surgical removal alone. Fractionated radiotherapy (RT) to a total dose of 35 Gy in five to seven fractions was used. RESULTS: A total of 73 local pterygium recurrences (9.9%) were noted. Of the recurrent cases, 80% were noted within 3 years after treatment. The 5- and 10-year probability of local control was 90% and 88%, respectively. The multivariate analysis for all cases demonstrated that gender, age, total radiation dose, recurrent pterygia, and interval between surgery and RT affected the overall local control rate. Late toxicities that might have been associated with strontium-90 RT included scleromalacia (scleral thinning) in nine eyes, adhesion of the eyelids in eight, cataracts in six, and scleral ulcer in five eyes. CONCLUSION: Fractionated strontium-90 RT to a total dose of approximately 35 Gy in five to seven fractions results in a similar local control rate as higher doses in other series, with an acceptable complication rate.

[Urbach-Wiethe syndrome: a case report]. / Síndrome de Urbach-Wiethe: relato de caso.

We present a case of Urbach-Wiethe syndrome with typical findings, including ocular lesions. A 15-year-old girl was referred to our department complaining of itchy eyelid lesions (moniliform blepharosis) associated with other systemic manifestations. Diagnosis was confirmed by performing skin biopsy. Artificial tears were prescribed, with partial relief of the symptom. The objective of the present study is to describe a typical case of Urbach-Wiethe syndrome attended at the Ophthalmologic Sector of the Medical School of Marília.

Síndrome de Urbach-Wiethe: relato de caso / Urbach-Wiethe syndrome: a case report

Apresentação de um caso de síndrome de Urbach-Wiethe com manifestações típicas, inclusive oculares. Paciente do sexo feminino, 15 anos, com quadro de prurido ocular relacionado à presença de lesões papuliformes em margens palpebrais (blefarose moniliforme), em associação com outras alterações sistêmicas. O diagnóstico foi confirmado por meio de biópsia cutânea e foi instituído uso de lágrimas artificiais, com alívio parcial do sintoma. O objetivo do trabalho é relatar um caso com manifestações características da doença atendido no Setor de Oftalmologia da Faculdade de Medicina de Marília.

We present a case of Urbach-Wiethe syndrome with typical findings, including ocular lesions. A 15-year-old girl was referred to our department complaining of itchy eyelid lesions (moniliform blepharosis) associated with other systemic manifestations. Diagnosis was confirmed by performing skin biopsy. Artificial tears were prescribed, with partial relief of the symptom. The objective of the present study is to describe a typical case of Urbach-Wiethe syndrome attended at the Ophthalmologic Sector of the Medical School of Marília.