Weight-adjusted caffeine and ß-blocker use in novice versus senior retina surgeons: a self-controlled study of simulated performance.

BACKGROUND/OBJECTIVES: Tremor and expertise are potentially influenced variables in vitreoretinal surgery. We investigated whether surgeon experience impacts the association of microsurgical performance with caffeine and ß-blockers weight-adjusted intake. SUBJECTS/METHODS: Novice and senior surgeons (<2 and >10 practice years, respectively) were recruited in this self-controlled, cross-sectional study. A simulator's task sequence was repeated over 2 days, 30 min after the following exposures: day 1, placebo, 2.5 mg/kg caffeine, 5.0 mg/kg caffeine, and 0.6 mg/kg propranolol; and day 2, placebo, 0.2 mg/kg propranolol, 0.6 mg/kg propranolol, and 5.0 mg/kg caffeine. Outcomes were total score (0-700, worst-best), simulation time (minutes), intraocular trajectory (centimeters), and tremor-specific score (0-100, worst-best). RESULTS: We recruited 15 novices (9 men [60%], 1.33 ± 0.49 practice years) and 11 seniors (8 men [72.7%], 16.00 ± 4.24 practice years). Novices performed worse after 2.5 mg/kg caffeine and improved following 0.2 mg/kg propranolol in total score (557 vs. 617, p = 0.009), trajectory (229.86 vs. 208.07, p = 0.048), time (14.9 vs. 12.7, p = 0.048), and tremor-score (55 vs. 75, p = 0.009). Surgical performance improved with propranolol post-caffeine but remained worse than 0.2 mg/kg propranolol in total score (570 vs. 617, p = 0.014), trajectory (226.59 vs. 208.07, p = 0.033), and tremor-score (50 vs. 75, p = 0.029). Seniors' tremor-score was lower after 2.5 mg/kg caffeine compared to 0.2 mg/kg propranolol (8 vs. 37, p = 0.015). Tremor-score following propranolol post-caffeine remained inferior to 0.6 mg/kg propranolol alone (17 vs. 38, p = 0.012). CONCLUSION: While caffeine and propranolol were associated with performance changes among novices, only tremor was affected in seniors, without dexterity changes. The pharmacologic exposure impact on surgical dexterity seems to be offset by increased experience.

A Polysomnographic Study of Effects of Sleep Deprivation on Novice and Senior Surgeons during Simulated Vitreoretinal Surgery.

PURPOSE: To assess the impact of a 3-hour polysomnography (PSG)-recorded night of sleep deprivation on next-morning simulated microsurgical skills among vitreoretinal (VR) surgeons with different levels of surgical experience and associate the sleep parameters obtained by PSG with Eyesi-generated performance. DESIGN: Self-controlled cohort study. PARTICIPANTS: Eleven junior VR surgery fellows with < 2 years of surgical experience and 11 senior surgeons with > 10 years of surgical practice. METHODS: Surgical performance was assessed at 7am after a 3-hour sleep-deprived night using the Eyesi simulator and compared with each subject's baseline performance. MAIN OUTCOME MEASURES: Changes in Eyesi-generated score (0-700, worst to best), time for task completion (minutes), tremor-specific score (0-100, worst to best), and out-of-tolerance tremor percentage. Polysomnography was recorded during sleep deprivation. RESULTS: Novice surgeons had worse simulated surgical performance after sleep deprivation compared with self-controlled baseline dexterity in the total score (559.1 ± 39.3 vs. 593.8 ± 31.7; P = 0.041), time for task completion (13.59 ± 3.87 minutes vs. 10.96 ± 1.95 minutes; P = 0.027), tremor-specific score (53.8 ± 19.7 vs. 70.0 ± 15.3; P = 0.031), and out-of-tolerance tremor (37.7% ± 11.9% vs. 28.0% ± 9.2%; P = 0.031), whereas no performance differences were detected in those parameters among the senior surgeons before and after sleep deprivation (P ≥ 0.05). Time for task completion increased by 26% (P = 0.048) in the post-sleep deprivation simulation sessions for all participants with a high apnea-hypopnea index (AHI) and by 37% (P = 0.008) among surgeons with fragmented sleep compared with those with normal AHI and < 10 arousals per hour, respectively. Fragmented sleep was the only polysomnographic parameter associated with a worse Eyesi-generated score, with a 10% (P = 0.005) decrease the following morning. CONCLUSIONS: This study detected impaired simulated surgical dexterity among novice surgeons after acute sleep deprivation, whereas senior surgeons maintained their surgical performance, suggesting that the impact of poor sleep quality on surgical skills is offset by increased experience. When considering the 2 study groups together, sleep fragmentation and AHI were associated with jeopardized surgical performance after sleep deprivation. FINANCIAL DISCLOSURE(S): The authors have no proprietary or commercial interest in any materials discussed in this article.

Biocompatibility of polyvinyl alcohol/trisodium trimetaphosphate as vitreous substitute in experimental vitrectomy model in rabbits.

Synthetic hydrogels have been proposed as vitreous substitutes recently. This study aims to evaluate the biocompatibility of polyvinyl alcohol (PVA) crosslinked with trisodium trimetaphosphate (SMTP) hydrogel in rabbit vitrectomized eyes. Seven animals were submitted to pars plana vitrectomy and the vitreous was replaced by PVA/SMTP hydrogel. Optical coherence tomography, fluorescein angiogram, clinical, and electrophysiological (ERG) examinations were analyzed at baseline, on postoperative days 7 and 30. The fellow eye was used as the control group. Hydrogel opacification was observed and ERG recordings were reduced in the hydrogel group in rod response, b-wave cone response and flicker. A histological analysis showed retinal disorganization, presence of multinucleated cells, and intraretinal hydrogel particles. The PVA/SMTP hydrogel showed poor biocompatibility. Novel biomaterials compounds should be analyzed in vivo.

Campimetry and visual changes after RHZE treatment for tuberculosis.

BACKGROUND: Tuberculosis (TB) caused by Mycobacterium tuberculosis has a high prevalence in Brazil (Global tuberculosis report 2020. Geneva: World Health Organization; 2020). The ethambutol-induced optic neuropathy damage is partly reversible, making its early diagnosis essential to reduce permanent visual damage. PURPOSE: To observe alterations in the computerized campimetry, Ishihara test and visual acuity secondary to rifampicin, isoniazid, pyrimethamine, ethambutol (RHZE) treatment. METHODS: Patients undergoing treatment with RHZE at the tuberculosis service of the Federal University of São Paulo were recruited from March 2019 to December 2020. The best-corrected visual acuity (VA) measurements, Ishihara test and visual fields were performed at baseline, monthly, until 2 weeks after treatment. RESULTS: Twenty-five patients were included. The VA decreased significantly (P = 0.0129) post-treatment compared to month 1. The mean deviation (MD) did not decrease significantly (P > 0.05); the pattern standard deviation (PSD) decreased post-treatment compared to month 1 (P = 0.0371). Changes in the Ishihara test increased significantly (P < 0.0001) in the second month. CONCLUSION: The VA and PSD decreased significantly after RHZE treatment. Changes in the Ishihara test were observed in the second month. TRIAL REGISTRATION: The Research Ethics Committee of Federal University of São Paulo, Paulista School of Medicine approved the study in March 2019. CAAE 04297018.4.0000.5505.

Characterization of PVA/glutaraldehyde hydrogels obtained using Central Composite Rotatable Design (CCRD).

Hydrogels are made from natural or synthetic polymers and, currently, they have many biomedical applications. In this work, the conditions for obtaining a hydrogel with similar physicochemical characteristics to the vitreous humor were defined using polyvinyl alcohol (PVA) and glutaraldehyde (GLUT) as cross-linker. The concentration of PVA and GLUT were modified, and their effect was analyzed in terms of the refractive index, density, and dynamic viscosity. The hydrogel which was obtained using 3.98% (w/V) of PVA, 3.13 mL (1.57 g) of GLUT in 100 mL, and the initial pH of 7.2 showed similar characteristics to the vitreous humor (density = 1.0174 ± 0.0050 g mL-1 , dynamic viscosity = 3.7425 ± 0.1800 mPa s and refractive index = 1.3410 ± 0.0010). The hydrogels were further investigated by rheological measurements, infrared spectroscopy, differential scanning calorimetry, X-ray diffraction and determination of swelling degree. The reticulation with GLUT promoted an increase in viscosity and glass transition temperature. On the other hand, it stimulated a decrease in the swelling degree, crystallinity, melting temperature, and intensity of the band related to the -OH bond, compared with the PVA without reticulation. The reticulated hydrogel displayed Newtonian behavior and a higher apparent viscosity than the PVA. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 1558-1566, 2018.

Incidence of anterior segment neovascularization during intravitreal treatment for macular edema secondary to central retinal vein occlusion.

PURPOSE:: To analyze the effects of injections of intravitreal triamcinolone acetonide (IVTA) and intravitreal bevacizumab (IVB) on the incidence rates of anterior segment neovascularization (ASN) and neovascular glaucoma (NVG) in patients with macular edema secondary to central retinal vein occlusion (CRVO). METHODS:: In this prospective, randomized, double-masked, sham-controlled study, 35 patients with macular edema following CRVO were randomized to intravitreal bevacizumab, intravitreal triamcinolone acetonide, or sham injections during the first 6 months of the study. The primary outcome was the incidence rate of ASN at month 6. The secondary outcomes were the mean changes from baseline in best-corrected visual acuity (BCVA) and central foveal thickness (CFT) on optical coherence tomography over time to month 12. RESULTS:: ASN developed in 8 (22.86%) eyes, including 5 (62.50%) eyes in the sham group and 3 (37.50%) eyes in the IVTA group, during 12 months of fol low-up (p=0.009). BCVA differed significantly (p<0.05) among the groups only at month 1. CFT did not differ significantly (p<0.05) among the groups over 12 months. NVG required surgery and developed in one eye despite laser treatment. CONCLUSION:: Early treatment with intravitreal antivascular endothelial growth factor therapy decreases the rates of ASN and NVG after CRVO.

Incidence of anterior segment neovascularization during intravitreal treatment for macular edema secondary to central retinal vein occlusion / Incidência de neovasos de segmento anterior durante o tratamento de edema macular secundário a oclusão da veia central da retina

ABSTRACT Purpose: To analyze the effects of injections of intravitreal triamcinolone acetonide (IVTA) and intravitreal bevacizumab (IVB) on the incidence rates of anterior segment neovascularization (ASN) and neovascular glaucoma (NVG) in patients with macular edema secondary to central retinal vein occlusion (CRVO). Methods: In this prospective, randomized, double-masked, sham-controlled study, 35 patients with macular edema following CRVO were randomized to intravitreal bevacizumab, intravitreal triamcinolone acetonide, or sham injections during the first 6 months of the study. The primary outcome was the incidence rate of ASN at month 6. The secondary outcomes were the mean changes from baseline in best-corrected visual acuity (BCVA) and central foveal thickness (CFT) on optical coherence tomography over time to month 12. Results: ASN developed in 8 (22.86%) eyes, including 5 (62.50%) eyes in the sham group and 3 (37.50%) eyes in the IVTA group, during 12 months of fol low-up (p=0.009). BCVA differed significantly (p<0.05) among the groups only at month 1. CFT did not differ significantly (p<0.05) among the groups over 12 months. NVG required surgery and developed in one eye despite laser treatment. Conclusion: Early treatment with intravitreal antivascular endothelial growth factor therapy decreases the rates of ASN and NVG after CRVO.

RESUMO Objetivo: Analisar as taxas de incidência de neovascularização do segmento anterior (NSA) e de glaucoma neovascular (GNV), em pacientes com edema macular secundário a oclusão de veia central da retina (OVCR), em tratamento com injeções intravítreas de triamcinolona (IVTA) ou bevacizumab (IVB). Métodos: Neste estudo prospectivo, randomizado, duplo mascarado e sham controlado, 35 pacientes com edema macular secundário a OVCR foram randomizados para IVB, IVTA ou para o grupo controle (sham), durante os 6 primeiros meses do estudo. O desfecho primário foi a taxa de incidência de NSA no mês 6. Os desfechos secundários foram alterações médias da acuidade visual corrigida (BCVA) e espessura foveal central (EFC) ao exame de tomografia de coerência óptica, até o mês 12. Resultados: NSA ocorreu em oito (22,86%) olhos, cinco (62,50%) olhos no grupo sham e três (37,50%) olhos no grupo tratado com injeções intravítreas de Triamcinolona, Não houve nenhum caso com NSA no grupo tratado com bevacizumab durante 12 meses de acompanhamento (p=0,009). A BCVA apresentou diferença estatisticamente significante (p<0,05) entre os grupos, somente no mês 1. A EFC não apresentou diferenças estatisticamente significantes (p<0,05) entre os grupos ao longo dos 12 meses. GNV ocorreu em um olho apesar do tratamento com laser e este paciente necessitou de intervenção cirúrgica. Conclusão: O tratamento precoce com injeções intravítreas de Anti VEGF podem diminuir as taxas de neovascularização do segmento anterior e glaucoma neovascular após oclusão de veia central da retina.

In vivo, in vitro toxicity and in vitro angiogenic inhibition of sunitinib malate.

PURPOSE: To evaluate the in vivo and in vitro toxicity of sunitinib malate, a multikinase inhibitor molecule. DESIGN: Experimental, Prospective, Controlled. METHODS: Human retinal pigment epithelial (ARPE-19) and human umbilical vein endothelialcells (HUVECS) were used in a culture toxicity test and exposed to different concentrations of sunitinib malate for 18 hours. The HUVECs also were cultured to evaluate the angiogenesis inhibitory effect of sunitinib malate. Fundus photography and angiographic, electrophysiologic, and histopathologic evaluations with light and electron microscopy were performed in two groups of five rabbits each that received different intravitreal concentrations of the drug. Each rabbit received 0.1 ml of sunitinib malate in the right eye (one group with 12.5 mg/ml, the other group with 25 mg/ml); all animals received 0.1 ml of physiologic saline solution in the left eye. After sacrifice, the eyes were enucleated and fixed with modified Karnovsky solution. RESULTS: No toxicity related to sunitinib malate was observed using an in vitro model with the 12.5 and 25 mg/ml solutions in HUVEC and ARPE cell cultures. No toxicity was observed in the in vivo model with 12.5 mg/ml, but light microscopy showed that the 25 mg/ml solution damaged the photoreceptors layer. No functional changes in the electroretinogram were observed in any group. CONCLUSIONS: Sunitinib malate 12.5 mg/ml caused no toxicity in in vivo and in vitro models, but the 25 mg/ml concentration caused retinal changes suggesting toxicity in the in vivo model. Further research with the drug is needed in models of ocular neovascularization.

[Technique of intravitreal drug injection for therapy of vitreoretinal diseases]. / Técnica para injeção intravítrea de drogas no tratamento de doenças vítreorretinianas.

Intravitreal injections are the standard technique applied in the treatment of some vitreoretinal diseases. In this paper the technique and complications of intravitreal injections are presented. In summary, the procedure involves various consecutive steps. Initially, days before the treatment topical antibiotics and acetazolamide may be prescribed for reduction of the ocular flora and intraocular pressure. Before the injection, the pupil should be dilated and topical anesthesia should be achieved. Injection shall be performed in the operating room under sterile conditions, the surgeon should wear surgical gloves and mask. The eye is then exposed with sterile blepharostat and sterile-drape thereby providing protection of the needle against the contact with contaminated lashes and lids. Injection is done 3.5 mm from the limbus through the pars plana. The needle should be inserted up to 6 mm into the vitreous cavity. Immediately after injection the patient must be examined by indirect ophthalmoscopy to verify central artery perfusion and complications as vitreous hemorrhage. Visual acuity better than light perception should be detected right after injection. If persistent central retinal artery occlusion is diagnosed, anterior chamber paracentesis should be performed. The patient may be discharged with an occlusive patch. Examination at the first postoperative day should exclude various complications such as endophthalmitis, and topical steroid and antibiotics should be prescribed for 7 days. Some complications encountered after intravitreal injections include retinal detachment, vitreous hemorrhage, cataract, uveitis, ocular hypertension, or endophthalmitis.

Técnica para injeção intravítrea de drogas no tratamento de doenças vítreorretinianas / Technique of intravitreal drug injection for therapy of vitreoretinal diseases

A injeção intravítrea é atualmente a técnica mais utilizada no tratamento de várias doenças vítreorretinianas. Neste artigo serão discutidas a técnica e complicações da injeção intravítrea de drogas no tratamento de doenças vítreorretinianas. Em resumo, a técnica envolve várias etapas. Inicialmente dias antes da injeção pode-se realizar aplicação de antibióticos e acetazolamida para prevenção de infecção e redução da pressão intra-ocular. Antes do procedimento deve-se dilatar a pupila e executar anestesia tópica com colírios ou gel anestésico. A antissepsia pré-operatória envolve aplicação de colírios de iodo-povidona 5 por cento no fundo de saco conjuntival ao menos 10 minutos antes do procedimento. A injeção deve ser realizada no centro cirúrgico com uso de luvas estéreis e máscara pelo cirurgião. O olho deve ser exposto com blefarostato estéril, e proteção com "sterile-drape" para evitar contato entre a agulha e pálpebras/cílios. A agulha deve ser posicionada no momento da injeção a 3,5 - 4 mm do limbo, e leve mobilização da conjuntiva com um cotonete estéril ou uma pinça facilitam a penetração da agulha através da conjuntiva e esclera. A agulha deve ser inserida gentilmente para dentro da cavidade vítrea até 6 mm de profundidade. Imediatamente após a injeção o paciente deve ser examinado por técnica de oftalmoscopia binocular indireta. Caso a acuidade visual seja ausência de percepção luminosa ou oclusão vascular arterial retiniana seja observada, terapias para diminuição da pressão como paracentese na camada anterior ou massagem por oculopressão diretamente sobre o globo ocular devem ser imediatamente tomadas. A alta ambulatorial deve ser realizada quando o cirurgião estiver ciente da ausência de complicações intra-operatórias; o paciente deverá sair do centro cirúrgico com curativo oclusivo. O paciente deve ser submetido a exame oftalmológico completo no primeiro dia pós-operatório quando associação de antibióticos com corticosteróides...

Intravitreal injections are the standard technique applied in the treatment of some vitreoretinal diseases. In this paper the technique and complications of intravitreal injections are presented. In summary, the procedure involves various consecutive steps. Initially, days before the treatment topical antibiotics and acetazolamide may be prescribed for reduction of the ocular flora and intraocular pressure. Before the injection, the pupil should be dilated and topical anesthesia should be achieved. Injection shall be performed in the operating room under sterile conditions, the surgeon should wear surgical gloves and mask. The eye is then exposed with sterile blepharostat and sterile-drape thereby providing protection of the needle against the contact with contaminated lashes and lids. Injection is done 3.5 mm from the limbus through the pars plana. The needle should be inserted up to 6 mm into the vitreous cavity. Immediately after injection the patient must be examined by indirect ophthalmoscopy to verify central artery perfusion and complications as vitreous hemorrhage. Visual acuity better than light perception should be detected right after injection. If persistent central retinal artery occlusion is diagnosed, anterior chamber paracentesis should be performed. The patient may be discharged with an occlusive patch. Examination at the first postoperative day should exclude various complications such as endophthalmitis, and topical steroid and antibiotics should be prescribed for 7 days. Some complications encountered after intravitreal injections include retinal detachment, vitreous hemorrhage, cataract, uveitis, ocular hypertension, or endophthalmitis.