Risk of adverse pregnancy and infant outcomes associated with prenatal Zika virus infection: a post-epidemic cohort in Central-West Brazil.

This study aimed to estimate the risks of adverse infant outcomes in the first year of life related to prenatal Zika virus (ZIKV) exposure. A prospective cohort of pregnant women with rash was recruited in Central-West Brazil in a post-epidemic period (January 2017 to April 2019). We evaluated participants' medical histories and performed ZIKV diagnostic testing using molecular (reverse transcription polymerase chain reaction [RT-PCR]) and serologic (immunoglobulin [Ig]M and plaque reduction neutralization tests [PRNT90]) assays. The ZIKV-positive group included both RT-PCR-confirmed cases as well as IgM and/or PRNT90-positive probable cases. Children were evaluated at birth and in the first 12 months of life. Transfontanellar ultrasound, central nervous system computed tomography, eye fundoscopy and retinography were performed. We estimated the absolute risk and 95% confidence interval (95% CI) of adverse infant outcomes among confirmed prenatally ZIKV-exposed children. Among 81 pregnant women with rash, 43 (53.1%) were ZIKV infected. The absolute risk of microcephaly among offspring of ZIKV-infected pregnant women was 7.0% (95% CI: 1.5-19.1), including the two cases of microcephaly detected prenatally and one detected postnatally. In total, 54.5% (95% CI: 39.8-68.7) of children in the ZIKV-exposed group had at least one ophthalmic abnormality, with the most frequent abnormalities being focal pigmentary mottling and chorioretinal atrophy or scarring. Our findings reinforce the importance of long-term monitoring of prenatally ZIKV-exposed children born apparently asymptomatic for Congenital Zika Syndrome.

Early occurrence of primary angle-closure glaucoma in a patient with retinitis pigmentosa and CRB1 gene variations / Manifestação precoce de glaucoma de ângulo fechado em paciente com retinopatia por mutação no gene CRB1

ABSTRACT We describe the case of a 15-year-old girl with decreased visual acuity associated with elevated intraocular pressure in both eyes and angle closure on gonioscopy. She also presented attenuation of retinal vessels and optic disc pallor with large excavation in the left eye. Ultrasound biomicroscopy revealed an anteriorly positioned ciliary body and absence of ciliary sulcus, confirming the plateau iris configuration. Spectral-domain optical coherence tomography revealed a bilateral cystoid macular edema. Genetic screening revealed heterozygous variants of the Crumbs homolog 1 (CRB1) gene (c.2843G>A and c.2506C>A). The patient underwent trabeculectomy for intraocular pressure control and topical treatment for macular edema. This case highlights the importance of performing gonioscopy and evaluating intraocular pressure in patients with a shallow anterior chamber despite young age. In addition, it also shows the importance of genetic screening, when available, in elucidating the diagnosis and providing patients and their families' information on the patient's prognosis and possible therapeutic options.

RESUMO Nós descrevemos um caso de uma paciente de 15 anos com queda de acuidade visual e aumento da pressão intraocular em ambos os olhos, juntamente com fechamento angular no exame de gonioscopia. Na fundoscopia a paciente apresentava atenuação dos vasos retinianos, palidez de disco e aumento de escavação em olho esquerdo. Ao exame da biomicroscopia ultrassônica, foi evidenciado corpo ciliar anteriorizado e ausência de sulco ciliar em ambos os olhos, relevando presença de íris em plateau. Ao exame de tomografia de coerência óptica, visualizamos presença de edema macular cistoide bilateral. O screening genético revelou heterozigose no gene CRB1 (c.2843G>A and c.2506C>A), confirmando o diagnóstico de retinose pigmentar. Este caso reforça a importância do exame de gonioscopia e da avaliação da pressão intraocular em pacientes em câmara rasa, mesmo em pacientes jovens. Além disso, mostra a importância do screening genético como ferramenta útil para elucidação diagnóstica.

The effect of bevacizumab, 5-fluorouracil, and triamcinolone on the healing modulation of surgical wounds in rats.

In this study, we aimed to analyze the effect of 5-fluorouracil, triamcinolone, and bevacizumab on scar modulation in an experimental rat model of surgical lesions. Rats (Rattus norvegicus albinus) were divided into four groups: bevacizumab, 5-fluorouracil + triamcinolone, bevacizumab + 5-fluorouracil + triamcinolone, and control (received no medication) groups. A linear, dorsal incision was created and sutured for the first intention wound healing, mimicking the surgical incision of upper blepharoplasty. Treatments were initiated on day 7, and the rats were euthanized on day 14. Only in the 5-fluorouracil + triamcinolone group was there a difference in the number of infiltrated monocytes. There was 56%, 86%, and 85% decrease in the number of neovessels in the bevacizumab, 5-fluorouracil + triamcinolone, and bevacizumab + 5-fluorouracil + triamcinolone groups, respectively, compared with the control. Picrosirius red staining showed higher collagen density and more organized collagen in the treatment groups than in the control group. Scar modulation was observed in all groups, but the 5-fluorouracil + triamcinolone group presented the best results. To our knowledge, this is the first study to evaluate the influence of three medications in combination on healing. When used together, these medications can prevent the development of unsightly scars, and are therefore promising alternatives to corticosteroids.

Early occurrence of primary angle-closure glaucoma in a patient with retinitis pigmentosa and CRB1 gene variations.

We describe the case of a 15-year-old girl with decreased visual acuity associated with elevated intraocular pressure in both eyes and angle closure on gonioscopy. She also presented attenuation of retinal vessels and optic disc pallor with large excavation in the left eye. Ultrasound biomicroscopy revealed an anteriorly positioned ciliary body and absence of ciliary sulcus, confirming the plateau iris configuration. Spectral-domain optical coherence tomography revealed a bilateral cystoid macular edema. Genetic screening revealed heterozygous variants of the Crumbs homolog 1 (CRB1) gene (c.2843G>A and c.2506C>A). The patient underwent trabeculectomy for intraocular pressure control and topical treatment for macular edema. This case highlights the importance of performing gonioscopy and evaluating intraocular pressure in patients with a shallow anterior chamber despite young age. In addition, it also shows the importance of genetic screening, when available, in elucidating the diagnosis and providing patients and their families' information on the patient's prognosis and possible therapeutic options.

Multimodal imaging in a patient with combined hamartoma of the retina and retina pigment epithelium / Imagem multimodal em paciente com hamartoma combinado da retina e epitélio pigmentar da retina

ABSTRACT Combined hamartoma of the retina and retinal pigment epithelium is a rare, benign intraocular tumor. Hamartoma of the retina and retinal pigment epithelium has been described in the literature as a condition presenting with variable retinal damage, ranging from partial epiretinal involvement to complete distortion of the retinal layers and retinal pigment epithelium. We report the case of an 8-year-old girl presenting with longstanding strabismus who was diagnosed with Hamartoma of the retina and retinal pigment epithelium based on multimodal imaging assessment. We explored the particular imaging findings from studies using spectral-domain optical coherence tomography, fundus autofluorescence, optical coherence tomography angiography, and fluorescein angiography.

RESUMO O hamartoma combinado de retina e epitélio pigmentar da retina consiste em um tumor intraocular raro com comportamento benigno. O hamartoma combinado de retina e epitélio pigmentar da retina foi descrito na literatura apresentando dano retiniano variável, desde o envolvimento epirretiniano parcial até distorção completa das camadas retinianas e do epitélio pigmentar da retina. Relatamos o caso de uma menina de 8 anos com estrabismo de longa data que foi diagnosticada com hamartoma combinado de retina e epitélio pigmentar da retina, com base na avaliação de imagem multimodal. Exploramos os achados de imagem específicos de estudos usando tomografia de coerência óptica de domínio espectral, autofluorescência, angiografia por tomografia de coerência óptica e angiografia fluorescente.

Multimodal imaging in a patient with combined hamartoma of the retina and retina pigment epithelium.

Combined hamartoma of the retina and retinal pigment epithelium is a rare, benign intraocular tumor. Hamartoma of the retina and retinal pigment epithelium has been described in the literature as a condition presenting with variable retinal damage, ranging from partial epiretinal involvement to complete distortion of the retinal layers and retinal pigment epithelium. We report the case of an 8-year-old girl presenting with longstanding strabismus who was diagnosed with Hamartoma of the retina and retinal pigment epithelium based on multimodal imaging assessment. We explored the particular imaging findings from studies using spectral-domain optical coherence tomography, fundus autofluorescence, optical coherence tomography angiography, and fluorescein angiography.

Pars plana vitrectomy and visual stimulation for treatment of vitreomacular traction secondary to toxoplasmosis retinochoroiditis in a 5-year-old child / Vitrectomia via pars plana e estimulação visual para tratamento da tração vitreomacular secundária à retinocoroidite por toxoplasmose em criança de 5 anos

ABSTRACT Objective: A unusual case of ocular toxoplasmosis with significant vitreomacular traction is reported. The patient improved significantly following pars plana vitrectomy combined with visual stimulation and occlusion therapy. Methods: The case of a 5-year-old girl with significant unilateral vision loss associated with vitreous condensation and macular traction is described. Results: Pars plana vitrectomy was carried out for vitreomacular traction release. This was followed by visual stimulation and occlusion therapy. Significant improvement was observed. Conclusion: Despite structural damage, the combination of properly indicated surgery and amblyopia management strategies allowed the achievement of maximum vision goals in this case, suggesting structural damage may be associated with functional amblyopia.

RESUMO Objetivo: Relata-se um caso de apresentação atípica de toxoplasmose ocular, com importante tração vitreomacular. A paciente apresentou melhora significativa após vitrectomia via pars plana, com estimulação visual e oclusão. Métodos: Descreve-se o caso de uma menina de 5 anos, com importante perda de visão unilateral associada à condensação vítrea e à tração macular. Resultados: Foi realizada vitrectomia via pars plana para alívio da tração vitreomacular, seguida de estimulação visual e oclusão. Foi observada melhora significativa. Conclusão: Apesar dos danos estruturais, a combinação de cirurgia bem indicada com estratégias de tratamento da ambliopia permitiu alcançar o máximo do potencial visual nesta paciente, sugerindo que os danos estruturais podem estar associados à ambliopia funcional.

Analysis of cytokines in the aqueous humor during intravitreal Ranibizumab treatment of diabetic macular edema.

This study aimed to analyze the concentrations of VEGF, b-FGF, TNF, interleukin (IL)-1, IL-6, IL-8, IL-10, and IL-12 in the aqueous humor of patients with diabetic macular edema with and without peripheral retinal ischemia and to ascertain the changes in the levels of these molecules during treatment with ranibizumab. A therapeutic, prospective, randomized interventional study was carried out. Twenty-four eyes from 24 patients were studied and divided into 3 groups. Group 1 (9 eyes) included patients with diabetic macular edema without peripheral ischemia. Group 2 (10 eyes) included patients with diabetic macular edema with peripheral ischemia. Group 3 (5 eyes), the control group, included patients without systemic and/or eye diseases. Patients in Groups 1 and 2 received 3 intravitreal injections of 2 mg/0.05 ml ranibizumab at an interval of approximately 30 days. Before administering the injections, the aqueous humor was collected. In the control group, aqueous humor was collected before facetectomy. During treatment, the median IL-6 concentration significantly increased in Group 1 but showed a slight but not significant decrease in Group 2. Interleukin 8 levels were significantly different at the end of treatment compared to the beginning in Groups 1 and 2. TNF, IL-1, IL-10, and IL-12 levels were practically unchanged in both groups. VEGF was significantly reduced at the end of the study in Groups 1 and 2. B-FGF was not detected in most of the studied patients, and in those with detectable levels, there was no significant variation. There was a significant increase in the median level of interleukin 6 in the group without ischemia and a significant decrease in VEGF in both groups. The cytokines TNF, IL-1, IL-10, and IL-12 did not show significant variation.

Use of computerized campimetry and/or optical coherence tomography for glaucoma diagnosis by non-glaucoma specialists / Uso da campimetria e/ou da tomografia de coerência óptica no diagnóstico do glaucoma por oftalmologistas generalistas

ABSTRACT Purpose: To compare the use of visual field and/or optical coherence tomography (OCT) combined with color retinography by non-glaucoma specialists for differentiating glaucoma from physiological cupping. Methods: Eighty patients with glaucoma or physiological cupping (40 of each) were randomized according to the examination used (GI: color retinography, GII: color retinography + visual field, GIII: color retinography + optical coherence tomography, GIV: color retinography + visual field + optical coherence tomography). Twenty non-specialist ophthalmologists diagnosed glaucoma from PowerPoint slide images, without direct patient examination. Results: Inter-examiner agreement was good for GII (ĸ: 0.63; 95%CI, 0.53-0.72), moderate for GIII (ĸ: 0.58; 95%CI, 0.48-0.68) and GIV (ĸ: 0.41; 95%CI, 0.31-0.51), and low for GI (ĸ: 0.30; 95%CI, 0.20-0.39) (p<0.001). Diagnostic accuracy was higher in GIII (15.8 ± 1.82) than GI (12.95 ± 1.46, p<0.001) and higher in GII (16.25 ± 2.02) than GI and GIV (14.10 ± 2.24) (both p<0.001). For glaucoma patients only, diagnostic accuracy in GII and GIII was superior to that in GI and GIV (both p<0.001). Sensitivity and specificity were 59% and 70.5% in GI; 86.5% and 76% in GII, 86.5% and 71.5% in GIII; and 68.5% and 72.5% in GIV, respectively. Accuracy was highest in GII (81.3% [95%CI, 77.1-84.8]), followed by GIII (79% [95%CI, 74.7-82.7]), GIV (70,5% [95%CI, 65.9-74.8]), and GI (64.8% [95%CI, 60.0-69.3]). Conclusions: Non-glaucoma specialists could not differentiate glaucoma from increased physiological cupping when using color retinography assessment alone. Diagnostic accuracy and inter-rater agreement improved significantly with the addition of visual field or optical coherence tomography. However, the use of both modalities did not improve sensitivity/specificity.(AU)

RESUMO Objetivos: Verificar a influência do campo visual e/ou tomografia de coerência óptica, quando analisados em associação à retinografia colorida, na diferenciação entre indivíduos com glaucoma daqueles com aumento fisiológico de escavação. Métodos: Oitenta pacientes com glaucoma ou aumento fisiológico de escavação (40 cada) foram randomizados de acordo com o exame testado (GI: retinografia colorida, GII: retinografia colorida + campo visual, GIII: retinografia colorida + tomografia de coerência óptica, GIV: retinografia colorida + campo visual + tomografia de coerência óptica). Vinte oftalmologistas não especialistas em glaucoma diagnosticaram glaucoma através de slides do PowerPoint, sem o exame direto do paciente. Resultados: A concordância interexaminador foi boa para o GII (ĸ: 0,63; 95%CI, 0,53-0,72), moderada para GIII (ĸ: 0,58; 95%CI, 0,48-0,68) e GIV (ĸ: 0,41; 95%CI, 0,31-0,51), e baixa para o GI (ĸ: 0,30; 95%CI, 0,20-0,39) (p<0,001). Acurácia diagnostica foi maior no GIII (15,8 ± 1,82) em comparação ao GI (12,95 ± 1,46, p<0,001) e o GII (16,25 ± 2,02) maior em comparação ao GI e GIV (14,10 ± 2,24) (para ambos, p<0,001). Para os pacientes com glaucoma, a acurácia diagnostica nos grupos GII e GIII foi superior do que em GI e GIV (ambos p<0,001). Sensibilidade e especificidade foram 59% e 70,5% no GI; 86,5% e 76% no GII, 86,5% e 71,5% no GIII; 68,5% e 72,5% no GIV, respectivamente. A acurácia foi maior no GII (81,3% [95%CI, 77,1-84,8]), seguido pelo GIII (79% [95%CI, 74,7-82,7]), GIV (70,5% [95%CI, 65,9-74,8]), e GI (64,8% [95%CI, 60,0-69,3]). Conclusões: A avaliação isolada da retinografia colorida por oftalmologistas não especialistas em glaucoma não pode diferenciar pacientes com glaucoma daqueles com aumento fisiológico de escavação. Houve aumento da acurácia diagnóstica e da concordância interobservador com o acréscimo do campo visual ou da tomografia de coerência óptica. Entretanto, o uso de ambas as modalidades não melhorou a sensibilidade/especificadade.(AU)

Use of computerized campimetry and/or optical coherence tomography for glaucoma diagnosis by non-glaucoma specialists.

PURPOSE: To compare the use of visual field and/or optical coherence tomography (OCT) combined with color retinography by non-glaucoma specialists for differentiating glaucoma from physiological cupping. METHODS: Eighty patients with glaucoma or physiological cupping (40 of each) were randomized according to the examination used (GI: color retinography, GII: color retinography + visual field, GIII: color retinography + optical coherence tomography, GIV: color retinography + visual field + optical coherence tomography). Twenty non-specialist ophthalmologists diagnosed glaucoma from PowerPoint slide images, without direct patient examination. RESULTS: Inter-examiner agreement was good for GII (ĸ: 0.63; 95%CI, 0.53-0.72), moderate for GIII (ĸ: 0.58; 95%CI, 0.48-0.68) and GIV (ĸ: 0.41; 95%CI, 0.31-0.51), and low for GI (ĸ: 0.30; 95%CI, 0.20-0.39) (p<0.001). Diagnostic accuracy was higher in GIII (15.8 ± 1.82) than GI (12.95 ± 1.46, p<0.001) and higher in GII (16.25 ± 2.02) than GI and GIV (14.10 ± 2.24) (both p<0.001). For glaucoma patients only, diagnostic accuracy in GII and GIII was superior to that in GI and GIV (both p<0.001). Sensitivity and specificity were 59% and 70.5% in GI; 86.5% and 76% in GII, 86.5% and 71.5% in GIII; and 68.5% and 72.5% in GIV, respectively. Accuracy was highest in GII (81.3% [95%CI, 77.1-84.8]), followed by GIII (79% [95%CI, 74.7-82.7]), GIV (70,5% [95%CI, 65.9-74.8]), and GI (64.8% [95%CI, 60.0-69.3]). CONCLUSIONS: Non-glaucoma specialists could not differentiate glaucoma from increased physiological cupping when using color retinography assessment alone. Diagnostic accuracy and inter-rater agreement improved significantly with the addition of visual field or optical coherence tomography. However, the use of both modalities did not improve sensitivity/specificity.

Novel Possible Protein Targets in Neovascular Age-Related Macular Degeneration: A Pilot Study Experiment.

Age-related macular degeneration (AMD) is among the world's leading causes of blindness. In its neovascular form (nAMD), around 25% of patients present further anatomical and visual deterioration due to persistence of neovascular activity, despite gold-standard treatment protocols using intravitreal anti-VEGF medications. Thus, to comprehend, the molecular pathways that drive choroidal neoangiogenesis, associated with the vascular endothelial growth factor (VEGF), are important steps to elucidate the mechanistic events underneath the disease development. This is a pilot study, a prospective, translational experiment, in a real-life context aiming to evaluate the protein profiles of the aqueous humor of 15 patients divided into three groups: group 1, composed of patients with nAMD, who demonstrated a good response to anti-VEGF intravitreal injections during follow-up (good responsive); group 2, composed of patients with anti-VEGF-resistant nAMD, who demonstrated choroidal neovascularization activity during follow-up (poor/non-responsive); and group 3, composed of control patients without systemic diseases or signs of retinopathy. For proteomic characterization of the groups, mass spectrometry (label-free LC-MS/MS) was used. A total of 2,336 proteins were identified, of which 185 were distinctly regulated and allowed the differentiation of the clinical conditions analyzed. Among those, 39 proteins, including some novel ones, were analyzed as potential disease effectors through their pathophysiological implications in lipid metabolism, oxidative stress, complement system, inflammatory pathways, and angiogenesis. So, this study suggests the participation of other promising biomarkers in neovascular AMD, in addition to the known VEGF.

Surgical results regarding the correction of macular hole with and without face-down posturing using 25% SF6 gas: a retrospective case series.

PURPOSE: This study aims to compare the anatomical success rates of vitrectomy and SF6 gas tamponade for macular hole surgery with and without postoperative face-down posturing. METHODS: This was an observational, longitudinal, and retrospective case series analysis. The study included 52 eyes from 52 patients who underwent pars plana vitrectomy with trypan blue-assisted internal limiting membrane peeling and 25% SF6 tamponade for stages 2, 3, and 4 macular holes. After surgery, all patients were provided with a postoperative postural regimen: 31 patients were instructed not to maintain face-down posturing, whereas 21 were instructed to maintain face-down posturing for 7 days. The primary outcome measure was the macular hole closure rate. Statistical analysis was performed using Epi Info 7.1. RESULTS: A total of 47 (90.3%) patients achieved hole closure. The nonface-down posturing group and face-down posturing group obtained closure rates of 90.3% and 90.4%, respectively; these rates were not significantly different. Statistical analysis revealed that no significant differences existed in sex, age, hole duration, hole stage, preoperative visual acuity, or postoperative visual acuity between the two groups. CONCLUSION: Our results suggest that macular hole surgery with the use of short duration gas (SF6) is safe and effective and that maintaining a postural orientation of nonface-down posturing is also safe. However, these recommendations should be assessed further in a prospective and randomized study to comprehensively delineate the associated benefits and risks.

Strabismic amblyopia: compliance with occlusion treatment in a tertiary hospital in Midwestern Brazil / Ambliopia estrabísmica: adesão ao tratamento oclusivo em hospital terciário no Centro-Oeste Brasileiro

Abstract Purpose: Study aimed to determine compliance of patients with strabismic amblyopia undergoing occlusion treatment, followed from January 1 st, 2011 to January 1 st, 2017 at an Ophthalmology Reference Center, and identify risk factors for poor compliance. Methods: Retrospective, consecutive cohort study. Compliance reported at each visit was related to visual acuity, family history, changes in occlusion schedules and in patients' care team during treatment. The patients were divided into two groups according to the compliance: poor compliance group and compliance group (subdivided in full compliance subgroup and partial compliance subgroup). Results: Age at treatment beginning vary from 3.7 to 13.7 years, esotropia was the most frequent deviation and the occlusion was realized from 5 to 7 hours a day. Of 220 patients, compliance was achieved by 193 (87.7%), 114 (51.8%) in full compliance subgroup and 79 (35.9%) in partial compliance subgroup, and 27 do not achieved compliance (12.3%). Poor compliance was significantly related to a history of epilepsy, higher rate of suspension of treatment due to inefficacy, higher evasion rate, lower recurrence, and lower rate of maintenance of prophylactic occlusion after treatment. Good compliance was related to family history of strabismus, higher recurrence rate, and higher maintenance of prophylactic occlusion after treatment. No relations were found between poor compliance and changes in occlusion schedules or in patients' care team during treatment. Conclusion: Compliance with occlusion treatment of strabismic ambliopia was similar to other studies that included refractive and strabismic amblyopia and not related to changes in occlusion schedules or in patients' care team during treatment. Family history of strabismus was a protective factor.

Resumo Objetivo: Determinar a adesão de pacientes com ambliopia estrabísmica submetidos a tratamento oclusivo, acompanhados em Centro de Referência em Oftalmologia do Centro-Oeste do Brasil, e identificar fatores de risco para baixa adesão. Métodos: Estudo de coorte retrospectivo e consecutivo. A adesão relatada em cada visita foi relacionada à acuidade visual, história familiar, mudanças no tempo de oclusão e na equipe de atendimento ao paciente durante o tratamento. Os pacientes foram divididos em dois grupos de acordo com a adesão: grupo de não-adesão e grupo adesão (subdividido em subgrupo adesão total e subgrupo adesão parcial). Resultados: A idade ao início do tratamento variou de 3,7 a 13,7 anos, o desvio mais frequente foi a esotropia, o tempo médio de oclusão foi de 5 a 7 horas por dia. Dos 220 pacientes, 193 (87,7%) obtiveram adesão, 114 (51,8%) no subgrupo de adesão total e 79 (35,9%) no subgrupo de adesão parcial, e 27 não aderiram (12,3%). A não-adesão foi relacionada à história de epilepsia, maior taxa de suspensão do tratamento devido à ineficácia, maior taxa de evasão, menor recorrência e menor taxa de manutenção da oclusão profilática pós tratamento. A boa adesão foi relacionada à história familiar de estrabismo, maior taxa de recorrência e maior manutenção da oclusão profilática pós tratamento. Não houve relação entre não-adesão e mudanças nos horários de oclusão ou na equipe de atendimento durante o tratamento. Conclusão: A adesão ao tratamento oclusivo da ambliopia estrabísmica foi semelhante aos estudos que incluíram ambliopia refracional e estrabísmica e não se correlacionou a mudanças no tempo de oclusão ou na equipe de atendimento. A história familiar de estrabismo foi um fator de proteção.

Pedicle internal limiting membrane flap technique for very large macular holes: a preliminary report.

BACKGROUND: Conventional vitrectomy technique for macular hole surgery has a good outcome in small and medium macular holes, but for very large macular holes (minimum linear diameter higher than 700 µm) other techniques were developed aiming to achieve greater rates of closure and visual acuity gain. The purpose of this article is to report the anatomical and functional outcomes of four very large macular hole (MH) cases which have undergone vitrectomy with the pedicle internal limiting membrane (ILM) flap technique. METHODS: This is a retrospective series of four patients with large MH who were treated with vitrectomy and the pedicle ILM flap technique. Comprehensive ophthalmologic evaluation was performed before surgery and included ETDRS best-corrected visual acuity (BCVA) and spectral domain optical coherence tomography (SD-OCT) for MH measures: height, minimum linear diameter (MLD) and external base diameter. The particular detail of this technique is related to ILM flap creation. During the peeling, the ILM was not removed completely from the retina but was left attached to the edges of the macular hole and subsequently trimmed with the vitrectomy probe using the scissors mode. RESULTS: Four patients with very large MH underwent PPV and the pedicle ILM flap technique was used to pursue macular closure. Median preoperative BCVA was 20/400 (range: 20/320 to 20/400) and median postoperative BCVA was 20/200 (range: 20/320 to 20/200). Of the 4 cases reported, 3 obtained anatomical closure (75%), and also presented BCVA improvement after surgery, considering the last follow-up visit of each case. No additional procedures were performed in either case. One patient demonstrated no anatomic and functional improvement. CONCLUSION: The present study describes the first Brazilian case series of very large MH treated by the inverted pedicle ILM flap technique. This technique was associated with anatomic and visual improvement in most cases, and represents an alternative therapeutic approach for large macular holes.Trial Registration Project registered in Plataforma Brasil with CAAE number 30163520.0.0000.5440 and approved in ethics committee   from  Ribeirão Preto Medical School Clinics Hospital, University of São Paulo-Ribeirão Preto, São Paulo, Brazil (appreciation number 3.948.426 gave the approval).

Surgical results regarding the correction of macular hole with and without face-down posturing using 25% SF6 gas: a retrospective case series / Resultados cirúrgicos para correção de buraco macular com gás SF6 a 25% com e sem orientação postural: Série retrospectiva de casos

ABSTRACT Purpose: This study aims to compare the anatomical success rates of vitrectomy and SF6 gas tamponade for macular hole surgery with and without postoperative face-down posturing. Methods: This was an observational, longitudinal, and retrospective case series analysis. The study included 52 eyes from 52 patients who underwent pars plana vitrectomy with trypan blue-assisted internal limiting membrane peeling and 25% SF6 tamponade for stages 2, 3, and 4 macular holes. After surgery, all patients were provided with a postoperative postural regimen: 31 patients were instructed not to maintain face-down posturing, whereas 21 were instructed to maintain face-down posturing for 7 days. The primary outcome measure was the macular hole closure rate. Statistical analysis was performed using Epi Info 7.1. Results: A total of 47 (90.3%) patients achieved hole closure. The nonface-down posturing group and face-down posturing group obtained closure rates of 90.3% and 90.4%, respectively; these rates were not significantly different. Statistical analysis revealed that no significant differences existed in sex, age, hole duration, hole stage, preoperative visual acuity, or postoperative visual acuity between the two groups. Conclusion: Our results suggest that macular hole surgery with the use of short duration gas (SF6) is safe and effective and that maintaining a postural orientation of nonface-down posturing is also safe. However, these recommendations should be assessed further in a prospective and randomized study to comprehensively delineate the associated benefits and risks.

RESUMO Objetivos: Comparar as taxas de sucesso anatômico da vitrectomia e tamponamento de gás SF6 na cirurgia de buraco macular com e sem a postura pronada pós-operatória. Métodos: Foi realizado um estudo observacional, longitudinal e retrospectivo de séries de casos. O estudo incluiu 52 olhos de 52 pacientes submetidos à vitrectomia posterior via pars-plana com peeling de membrana limitante interna auxiliada por azul trypan e tamponamento com gás SF6 a 25% para os estágios 2, 3 e 4 dos buracos maculares. Após a cirurgia, todos os pacientes foram orientados a manter um regime postural pós-operatório: 31 pacientes foram orientados a não realizar posição pronada de cabeça, enquanto 21 foram orientados a manter uma pronada pós-operatória por 7 dias. O objetivo principal foi a análise da taxa de fechamento do buraco macular. A análise estatística foi realizada usando Epi-Info 7.1. Resultados: Um total de 47 (90,3%) pacientes obtiveram fechamento do buraco macular. O grupo de postura não pronada e o grupo de postura pronada obtiveram taxas de fechamento de 90,3%, e 90,4%, respectivamente; essas taxas não foram significativamente diferentes. A análise estatística revelou que não houve diferenças significativas relacionadas ao gênero, idade, duração do buraco macular, estágio do buraco macular, acuidade visual corrigida pré e pós-operatória entre os dois grupos. Conclusão: Nossos resultados sugerem que a cirurgia para buraco macular com o uso de gás de curta duração (SF6) é segura e eficaz e que a manutenção de uma orientação pós-operatória de não-pronada também é segura. No entanto, essas recomendações devem ser avaliadas em um estudo prospectivo e randomizado para delinear de forma abrangente os riscos e benefícios associados.

INTRAVITREAL DEXAMETHASONE IMPLANT MIGRATION INTO THE ANTERIOR CHAMBER: A Multicenter Study From the Pan-American Collaborative Retina Study Group.

PURPOSE: To establish the prevalence and risk factors for intravitreal dexamethasone implant migration into the anterior chamber in eyes with macular edema. METHODS: This was a multicenter, retrospective, observational chart review of data that included patients with macular edema who had been treated with at least one intravitreal dexamethasone injection. Patients with incomplete chart information during the follow-up period were excluded. RESULTS: The prevalence of implant migration in 468 patients, considering the number of injections, was 1.6%, with significant associations between implant migration and cataract surgery (P = 0.043) and intraocular lens status (P = 0.005) and a trend toward statistical significance (P = 0.057) with vitrectomy. A higher rate of implant migration into the anterior chamber was observed in vitrectomized eyes (4.8%) when compared with patients who did not undergo a vitrectomy (1.6%). The implants that migrated were removed with forceps with/without viscoelastic expression or with 20-gauge cannulas connected to the vitreous cutter machine. CONCLUSION: The risk of implant migration into the anterior chamber was 1.6%. Risk factors were a history of cataract surgery or vitrectomy and aphakia. When anterior migration occurs, rapid removal is advised, especially if corneal edema is present.

In vivo and in vitro toxicity evaluation of liposome-encapsulated sirolimus.

BACKGROUND: To evaluate the in vivo and in vitro toxicity of a new formulation of liposome-encapsulated sirolimus (LES). METHODS: In vitro experiments were done using ARPE-19 and HRP cells. An MTT assay was used to determine cell metabolic activity and a TUNEL assay for detecting DNA fragmentation. In vivo experiments were conducted on New Zealand albino rabbits that received intravitreal injections of empty liposomes (EL) or different concentrations of LES. Histopathological and immunohistochemical analyses were performed on the rabbit's eyes following injection. RESULTS: Eighteen eyes of nine rabbits were used. MTT assay cell viability was 95.04% in group 1 (12.5 µL/mL LES). 92.95% in group 2 (25 µL/mL LES), 91.59% in group 3 (50 µL/mL LES), 98.09% in group 4 (12.5 µL/mL EL), 95.20% on group 5 (50 µL/mL EL), 98.53% in group 6 (50 µL/mL EL), and 2.84% on group 8 (50 µL/mL DMSO). There was no statistically significant difference among groups 1 to 7 in cell viability (p = 1.0), but the comparison of all groups with group 8 was significant (p < 0.0001). The TUNEL assay comparing two groups was not statistically significant from groups 1 to 7 (p = 1.0). The difference between groups 1 to 7 and group 8 (p < 0.0001) was significant. Histopathological changes were not found in any group. No activation of Müller cells was detected. CONCLUSION: A novel formulation of LES delivered intravitreally did not cause in vitro toxicity, as evaluated by MTT and TUNEL assays, nor in vivo toxicity as evaluated by histopathology and immunohistochemistry in rabbit eyes.