Exploring Modern Mechanism of Treating Diabetic Retinopathy and Coronary Heart Disease from Perspective of Blood Stasis Under Viewpoint of Treating Different Diseases with the Same Method / 中国实验方剂学杂志

Diabetic retinopathy（DR） and coronary heart disease（CHD） are both major chronic vascular complications that seriously jeopardize the health of the population and often occur together in clinical practice， it is of great clinical value to actively explore the association between the two in the process of disease development and methods of prevention and treatment of modern medicine and traditional Chinese medicine（TCM）. According to TCM， the heart and eyes physiologically communicate with each other by taking Qi， blood and veins as bridges， blood stasis obstructing collaterals is the common TCM etiology of DR and CHD， whose mechanism involves inflammation， oxidative stress and endothelial dysfunction. Promoting blood circulation and removing blood stasis plays an important role in the same treatment for different diseases and prevention and treatment of comorbidities， possibly by inhibiting the expression of interleukin-1β（IL-1β）， endothelin-1（ET-1） and hypoxia inducible factor-1α/vascular endothelial growth factor（HIF-1α/VEGF）， regulating phosphatidylinositol 3-kinases/protein kinase B/mammalian target of rapamycin（PI3K/Akt/mTOR） pathway， initiating adenosine monophosphate（AMP）-activated protein kinase/silent information regulator 1（AMPK/SIRT1） and nuclear transcription factor erythroid 2-related factor 2/heme oxygenase-1（Nrf2/HO-1） signaling pathways， inhibiting Hippo/Yes-associated protein（Hippo/YAP） signaling pathway， inhibiting mitochondrial permeability transition pore and anti-platelet agglutination for treating DR and CHD， which provides a multi-component， multi-pathway and multi-target selection strategies and ideas for the prevention and treatment of DR and CHD by TCM from a biological perspective. Based on this， subsequent studies should focus on constructing clinically relevant comorbidity models， conducting multicenter prospective studies， and fully utilizing artificial intelligence technology to gain a deeper understanding of the relationship between the two diseases， so as to elucidate the mechanism of promoting blood circulation and removing blood stasis in preventing and treating panvascular diseases.

Optical coherence tomography angiography manifestations of different degrees of nonproliferative diabetic retinopathy / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To investigate the differences in varying stages of non-proliferative diabetic retinopathy(NPDR)using optical coherence tomography angiography(OCTA).METHODS: Cross-sectional study. A total of 77 cases(77 eyes)of diabetic patients were included, and they were divided into non-diabetic retinopathy(NDR; 23 eyes)and non-proliferative diabetic retinopathy(NPDR; 54 eyes)groups, further subdivided into mild NPDR(20 eyes), moderate NPDR(20 eyes), and severe NPDR(14 eyes). Foveal avascular zone(FAZ)area, superficial and deep capillary plexus densities(SSP and DSP), and visual acuity(LogMAR)were compared between NDR and NPDR groups. Furthermore, the visual acuity, FAZ area and levels of SSP and DSP were compared in different degrees of NPDR. Correlation analysis were conducted to elucidate relationships between FAZ area, visual acuity, SSP, DSP, and severity of the disease.RESULTS: Compared with the NDR group, the visual acuity(LogMAR)and macular FAZ area increased, while SSP and DSP were decreased in the NPDR group(P<0.05); there were significant differences in visual acuity, FAZ area and SSP and DSP levels in different degrees of NPDR(P<0.05). Visual acuity(LogMAR)and FAZ area displayed a positive correlation with the severity of disease, while SSP and DSP showed a negative correlation.CONCLUSION: With the progression of NPDR, the visual acuity(LogMAR)and FAZ area increased, and the SSP and DSP decreased.

Research progress of adipokines and diabetic retinopathy / 国际眼科杂志(Guoji Yanke Zazhi)

Diabetic retinopathy(DR)is one of the common microangiopathy in diabetes and the main cause of blindness in adults. It can be seen that it is very important to find the specific target of DR prevention and treatment. Adipose tissue is not only an energy storage tissue, but also an active endocrine organ, which can release a variety of cytokines, called adipokines. Studies have shown that adipokines play an important role in the occurrence and development of DR. Adipokines can not only directly act on vascular endothelium through blood circulation, but also indirectly affect vascular endothelial function by affecting the activity of sympathetic nervous system and insulin sensitivity, which leads to dysfunction of vascular endothelial cells, increased retinal vascular permeability, neurodegeneration and neovascularization, and finally leads to the destruction of blood-retinal barrier. In recent years, the role of some new adipokines in DR has been paid more and more attention. This paper reviews the related research of several new adipokines in DR.

Influencing factors of telangiectasia secondary to diabetic retinopathy / 国际眼科杂志(Guoji Yanke Zazhi)

AIM:To investigate the influencing factors of abnormal telangiectasia secondary to diabetic retinopathy(DR).METHODS: Prospective studies. A total of 153 cases(240 eyes)with DR treated in our hospital from January 2021 to January 2023 were selected to analyze the risk factors of abnormal telangiectasia secondary to DR and its predictive efficacy.RESULTS: The patients were divided into dilated group(77 eyes of 40 cases)and non-dilated group(163 eyes of 113 cases)according to whether they had secondary abnormal telangiectasia. There were significant differences in diabetic macular edema, hard exudates grade and fasting blood glucose level between the two groups(P<0.05). Logistic regression analysis showed that diabetic macular edema, high hard exudates grade and high blood glucose level were the risk factors for abnormal telangiectasia secondary to DR(P<0.05).CONCLUSION: The occurrence of telangiectasia secondary to DR may be related to diabetic macular edema, grade 3 hard exudates and high blood glucose level.

Research progress on morphology of macular foveal avascular zone in ocular diseases based on optical coherence tomography angiography measurement / 国际眼科杂志(Guoji Yanke Zazhi)

The foveal avascular zone(FAZ)is the most sensitive region of the retina, which is interconnected by the macular capillary plexus. Its morphology can indirectly reflect the alterations of macular microcirculation. With strong repeatability and reliability, optical coherence tomography angiography(OCTA)can non-invasively visualize and quantify the FAZ. The great value of OCTA makes it an important supplemental examination tool in ophthalmology and other professions. The area and perimeter of FAZ have been demonstrated to be an effective clinical diagnostic indicator in high myopia, diabetic retinopathy, glaucoma and other ocular diseases. In recent years, the geometry of FAZ has also proven to have clinical value. The parameters describing the geometry of FAZ, such as circularity index, acircularity index and axial ratio, provide a new perspective for ocular disease research. The comprehensive investigation of the morphological characteristics of the FAZ is helpful to explore the pathological mechanism of the occurrence and development of ocular diseases, predict preclinical changes, make pathological stages of the disease precise, and provide a theoretical basis for monitoring the disease's progression and assessing patients' visual prognosis.

Quantitative analysis of macular capillaries in diabetic patients using optical coherence tomography angiography / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To quantify early changes of macular capillary parameters in type 2 diabetic patients using optical coherence tomography angiography(OCTA).METHODS: Retrospective case study. A total of 49 healthy subjects, 52 diabetic patients without retinopathy(noDR)patients, and 43 mild nonproliferative diabetic retinopathy(mNPDR)patients were recruited. Capillary perfusion density, vessel length density(VLD), and average vessel diameter(AVD)were calculated from macular OCTA images(3 mm×3 mm)of the superficial capillary plexus after segmenting large vessels and the deep capillary plexus. Parameters were compared among control subjects, noDR, and mNPDR patients. The area under the receiver operating characteristic curve estimated the abilities of these parameters to detect early changes of retinal microvascular networks.RESULTS: Significant differences were found in the VLD and AVD among the three groups(P<0.001). Compared with the control group, the noDR group had significantly higher AVD(P<0.05). VLD of both layers in patients of mNPDR group was significant decreased compared with that of noDR group(all P<0.01). Deep AVD had a higher area under the curve(AUC)of 0.796 than other parameters to discriminate the noDR group from the healthy group. Deep AVD had the highest AUC of 0.920, followed by that of the deep VLD(AUC=0.899)to discriminate the mNPDR group from the healthy group.CONCLUSIONS: NoDR patients had wider AVD than healthy individuals and longer VLD than mNPDR patients in both layers. When compared with healthy individuals, deep AVD had a stronger ability than other parameters to detect early retinal capillary impairments in noDR patients.

Compound anisodine combined with retinal laser photocoagulation for the treatment of severe non-proliferative diabetic retinopathy / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To investigate the clinical efficacy of the compound anisodine combined with retinal laser photocoagulation in the treatment of severe non-proliferative diabetic retinopathy(NPDR). METHODS: According to the retrospective study, totally 120 eyes of patients with severe NPDR who admitted to Daxing Teaching Hospital Affiliated to Capital Medical University from May 2023 to July 2023 were selected. The patients were divided into the observation group and the control group according to treatment methods, with 60 eyes in each group. The observation group was treated with panretinal photocoagulation combined with the compound anisodine injection. The control group was only treated with panretinal photocoagulation. The optical coherence tomography angiography(OCTA)and optical coherence tomography(OCT)were used to quantitatively analyze the fundus retinal structure and blood flow. Furthermore, the best corrected visual acuity(BCVA), superficial vascular density(SVD), deep vascular density(DVD), choroidal blood flow density and central macular foveal retinal thickness(CMT)were compared before treatment and at 1 d, 1 and 2 mo after treatment.RESULTS:At 2 mo postoperatively, the rate of visual improvement and the BCVA in the observation group of patients were significantly better than those of the control group, and the incidence of macular edema in the observation group was significantly lower than the control group(P<0.05). The BCVA at 1 and 2 mo after treatment were significantly higher than those before treatment in both groups(P<0.05). The SVD in the observation group was better than the control group at 1 d, 1 and 2 mo after treatment(all P<0.05). The DVD and choroidal flow density in the observation group were better than those of the control group at 1 d after treatment(all P<0.05). The CMT of the observation group was smaller than that of the control group at 1 d after treatment(P<0.05).CONCLUSION:Compound anisodine can effectively improve the fundus microcirculation after panretinal photocoagulation and reduce the incidence of macular edema, thus promoting the visual function.

Association of diabetic retinopathy with anxiety and depression / 国际眼科杂志(Guoji Yanke Zazhi)

As society advances and living standards improve, there is a growing emphasis on the impact of mental health on illness and the interaction between them. Diabetes mellitus is one of the most common underlying diseases, and it is often accompanied by depression and anxiety. There are also many complications of diabetes, such as diabetic retinopathy(DR). DR is the leading cause of vision loss in diabetes. Vision loss inevitably increases anxiety and/or depression, which in turn may directly or indirectly affect the treatment or progression of patients with DR. This article reviews how to determine the anxiety and depression status of patients with DR, related assessment tools and methods, and their interaction with the treatment of DR. The interaction of anxiety-depressive states with DR treatment was also discussed. This review aims to raise awareness of the mental health of patients with DR, enhance doctor-patient communication and build doctor-patient trust, thus enhancing treatment adherence and clinical efficacy for individuals with DR and helping them to improve the quality of life.

Role of microglia in retinal neurovascular unit of diabetic retinopathy / 国际眼科杂志(Guoji Yanke Zazhi)

Diabetic retinopathy(DR)represents the primary cause of blindness among the global working-age population, and the disruption of the blood-retinal barrier is a crucial factor. Research in recent years has elucidated that DR transcends the scope of a mere microvascular disorder into a complex interplay of retinal glial cells and neurodegeneration microvascular pathology. Neuronal damage may precede vascular endothelial changes in the retinal neurovascular unit(RNVU)in the early stage of DR, and glial cell activation further exacerbates vascular barrier dysfunction. Retinal microglia are immune cells that reside in the retina and are involved in chronic inflammatory responses induced by long-term exposure to high glucose levels. Microglia secrete various inflammatory factors in response to high glucose levels, which can lead to the destruction of the blood-retinal barrier structure, increased neuronal apoptosis, and altered gliosis of Muller cells, thus affecting the retina's homeostatic balance. The RNVU has received increasing attention in recent years as a unitary structural study, and the mechanism of microglia in the RNVU and the progress of the study are reviewed.

Nomogram including serum ferritin to predict the occurrence of diabetic retinopathy / 国际眼科杂志(Guoji Yanke Zazhi)

AIM:To establish a nomogram model to predict the effect of serum ferritin on diabetic retinopathy and evaluate the model.METHODS:A total of 21 variables, including ferritin, were screened by univariate and multivariate regression analysis to determine the risk factors of diabetic retinopathy. A nomogram prediction model was established for evaluation and calibration.RESULTS:Ferritin, duration of diabetes, hemoglobin, urine microalbumin, regularity of medication and body mass index were included in the nomogram model. The consistency index of the prediction model with serum ferritin was 0.813(95%CI: 0.748-0.879). The calibration curves of internal and external verification showed good performance, and the probability of the threshold suggested by the decision curve was in the range 10% to 90%. The model had a high net profit value.CONCLUSIONS:Serum ferritin is an important risk factor for diabetic retinopathy. A new nomogram model, which includes body mass index, duration of diabetes, ferritin, hemoglobin, urine microalbumin and regularity of medication, has a high predictive accuracy and could provide early prediction for clinicians.

Research progress of m6A methylation modification in ocular diseases / 国际眼科杂志(Guoji Yanke Zazhi)

N6-methyladenosine(m6A), the most common, abundant, and conserved RNA modification in eukaryotic cells, regulates RNA splicing, stability, output, degradation and translation through m6A methyltransferase, m6A demethylase, and m6A methylated binding proteins. Recent studies have found that abnormal m6A methylation may mediate a variety of pathological processes in eyes and participate in the occurrence and development of metabolic, inflammatory, degenerative ocular diseases and ocular tumors, such as diabetic retinopathy, cataract, age-related macular degeneration and uveal melanoma. This review aims to summarize the roles of m6A methylation modification in ocular cells and ocular diseases, elucidate the potential molecular mechanisms of m6A methylation in ocular diseases, so as to encourage innovative approaches in the treatment of these ocular diseases.

Treatment of Diabetic Retinopathy with Blood Stasis， Collateral Obstruction， and Qi and Yin Deficiency Syndrome with Tongluo Mingmu Capsules： A Randomized， Double-blind， and Multi-center Phase Ⅲ Clinical Trial / 中国实验方剂学杂志

ObjectiveTo evaluate the clinical efficacy and safety of Tongluo Mingmu capsules in the treatment of diabetic retinopathy with blood stasis， collateral obstruction， and Qi and Yin deficiency syndrome. MethodA randomized， double-blind， positive-control， and multi-center clinical trial design method was used. 416 patients with diabetic retinopathy with blood stasis， collateral obstruction， and Qi and Yin deficiency syndrome in four test centers were included （the ratio of the treatment group to the control group was 3∶1）. On the basis of standardized hypoglycemic treatment， the treatment group was given both four Tongluo Mingmu capsules and two Calcium Dobesilate capsule agents three times a day， while the control group were given both two Calcium Dobesilate capsules and four Tongluo Mingmu capsule agents three times a day. The course of treatment was 12 weeks. The curative effect of Tongluo Mingmu capsules was evaluated by comparing the comprehensive curative effect of diabetic retinopathy， traditional Chinese medicine（TCM） syndrome score， corrected visual acuity， fundus changes， fundus fluorescence angiography， and other curative effect indexes before and after treatment in the two groups. At the same time， general examination， laboratory examination， and adverse events were performed to evaluate the safety of the drug. ResultThe baseline demographic data and disease characteristics of the treatment group and the control group were balanced and comparable， with the difference not statistically significant. After 12 weeks of treatment， the total effective rate of the comprehensive curative effect of diabetic retinopathy in the treatment group （61.0%， 189/310） was better than that in the control group （44.1%， 45/102）， and the difference was statistically significant （χ2=8.880， P<0.01）. The total effective rate of TCM syndromes in the treatment group （88.4%， 259/293） was better than that in the control group （69.9%， 65/93）， and the difference was statistically significant （χ2=17.927， P<0.01）. The disappearance rate of dry eyes （χ2=8.305）， dull complexion （χ2=4.053）， lassitude （χ2=10.267）， shortness of breath （χ2=8.494）， and dry stool （χ2=8.657） in the treatment group was higher than that in the control group， and the difference between the groups was statistically significant （P<0.05， P<0.01）. In terms of improving corrected visual acuity （χ2=8.382）， fundus changes （χ2=6.026） ， the treatment group was significantly better than the control group （P<0.05）. During the trial， the incidence of adverse events in the treatment group and the control group was 1.3% and 2.9%， respectively. There was no significant difference between the two groups. In addition， there were no serious adverse events and adverse events leading to withdrawal in both groups. ConclusionTongluo Mingmu capsules can improve the comprehensive curative effect of diabetic retinopathy and enhance the efficacy of TCM syndromes， visual acuity， fundus changes， and fundus fluorescein angiography， with great safety. Therefore， it can provide a new alternative therapeutic drug for patients with diabetic retinopathy.

Advances of metabolomics in ocular diseases / 国际眼科杂志(Guoji Yanke Zazhi)

Ocular diseases pose a significant challenge to global health. The field of metabolomics, which involves the systematic identification and quantification of metabolites within a biological system, has emerged as a promising research approach for unraveling disease mechanisms and discovering novel biomarkers. Through its application, metabolomics has yielded valuable knowledge pertaining to the initiation and advancement of various ocular diseases. This review presents an overview of metabolomics and examines recent research progess in four ocular diseases, specifically diabetic retinopathy, age-related macular degeneration, glaucoma, and dry eye, summarizing potential biomarkers and metabolic pathways associated with these diseases. Additionally, this review offers insights into the future prospects of utilizing metabolomics for the management and treatment of ocular diseases.

Role of complement protein regulatory targets in diabetic retinopathy and its clinical research progress / 国际眼科杂志(Guoji Yanke Zazhi)

The complement system is a protein response system with a precise regulatory mechanism, which has the functions of mediating inflammation, regulating immune response, dissolving cells and clearing immune complexes. Diabetic retinopathy(DR)is a common and severe ocular complication of diabetes and one of the common irreversible blinding eye diseases in ophthalmology, and its pathogenesis is complex, including hypoxia, oxidative stress, inflammation and abnormal polyol metabolism pathway. In recent years, there has been more and more evidence that dysregulation and inflammation of immune system are important factors in the pathogenesis of DR, and a variety of complement proteins play an important role in key processes such as inflammation regulation and angiogenesis. Therefore, the central purpose of this review is to discuss the role of the complement system and related regulatory proteins in DR, with the aim of elucidating the close relationship between the complement proteins and the occurrence and development of DR, and providing important references and new ideas for the prevention and treatment of DR. At the same time, the clinical research of complement system-targeted drugs is further elaborated.

Preoperative co-application of bevacizumab and tissue plasminogen activator in vitrectomy for proliferative diabetic retinopathy

ABSTRACT Purpose: To investigate the clinical benefits of the co-application of bevacizumab and tissue plasminogen activator as adjuncts in the surgical treatment of proliferative diabetic retinopathy. Methods: Patients who underwent vitrectomy for proliferative dia-betic retinopathy complications were preoperatively given in-travitreal injection with either bevacizumab and tissue plasminogen activator (Group 1) or bevacizumab alone (Group 2). Primary outcomes were surgery time and number of intraoperative iatrogenic retinal breaks. Secondary outcomes included changes in the best-corrected visual acuity and postoperative complications at 3 months postoperatively. Results: The mean surgery time in Group 1 (52.95 ± 5.90 min) was significantly shorter than that in Group 2 (79.61 ± 12.63 min) (p<0.001). The mean number of iatrogenic retinal breaks was 0.50 ± 0.59 (0-2) in Group 1 and 2.00 ± 0.83 (0-3) in Group 2 (p<0.001). The best-corrected visual acuity significantly improved in both groups (p<0.001). One eye in each group developed retinal detachment. Conclusion: Preoperative co-application of bevacizumab and tissue plasminogen activator as adjuncts in the surgical treatment of proliferative diabetic retinopathy shortens the surgery time and reduces the number of intraoperative iatrogenic retinal breaks.

Results of office-based fluid-air exchange for postvitrectomy hemorrhage in diabetic retinopathy

ABSTRACT Purpose: This study aimed to evaluate the efficacy and clinical outcomes of a one-way fluid-air exchange procedure for the treatment of postvitrectomy diabetic vitreous hemorrhage in patients with proliferative diabetic retinopathy. Methods: This retrospective study included 233 patients with proliferative diabetic retinopathy, who underwent vitrectomy. A one-way fluid-air exchange procedure was performed in 24 eyes of 24 (10.30%) patients with persistent vitreous cavity rebleeding after the operation. Preprocedural and postprocedural best-corrected visual acuity values were achieved. Complications occurring during and after the procedure were analyzed. Results: Significant visual improvement was observed 1 month after the one-way fluid-air exchange procedure (2.62 ± 0.60 LogMAR at baseline vs. 0.85 ± 0.94 LogMAR at postprocedure, p<0.0001). Moreover, 19 (79.17%) eyes needed the procedure once, and 5 (20.83%) eyed had the procedure more than twice. In 3 (12.50%) eyes, reoperation was eventually required because of persistent rebleeding despite several fluid-air exchanges. No complication was observed during the follow-up. Conclusions: The one-way fluid-air exchange procedure can be an excellent alternative to re-vitrectomy for patients with proliferative diabetic retinopathy suffering from postvitrectomy diabetic vitreous hemorrhage by removing the hemorrhagic contents directly and achieving fast recovery of visual function without apparent complications.

Diagnóstico da retinopatia diabética por inteligência artificial por meio de smartphone / Diagnosis of diabetic retinopathy by artificial intelligence using smartphone

RESUMO Objetivo: Obter imagens de fundoscopia por meio de equipamento portátil e de baixo custo e, usando inteligência artificial, avaliar a presença de retinopatia diabética. Métodos: Por meio de um smartphone acoplado a um dispositivo com lente de 20D, foram obtidas imagens de fundo de olhos de pacientes diabéticos; usando a inteligência artificial, a presença de retinopatia diabética foi classificada por algoritmo binário. Resultados: Foram avaliadas 97 imagens da fundoscopia ocular (45 normais e 52 com retinopatia diabética). Com auxílio da inteligência artificial, houve acurácia diagnóstica em torno de 70 a 100% na classificação da presença de retinopatia diabética. Conclusão: A abordagem usando dispositivo portátil de baixo custo apresentou eficácia satisfatória na triagem de pacientes diabéticos com ou sem retinopatia diabética, sendo útil para locais sem condições de infraestrutura.

ABSTRACT Introduction: To obtain fundoscopy images through portable and low-cost equipment using artificial intelligence to assess the presence of DR. Methods: Fundus images of diabetic patients' eyes were obtained by using a smartphone coupled to a device with a 20D lens. By using artificial intelligence (AI), the presence of DR was classified by a binary algorithm. Results: 97 ocular fundoscopy images were evaluated (45 normal and 52 with DR). Through AI diagnostic accuracy around was 70% to 100% in the classification of the presence of DR. Conclusion: The approach using a low-cost portable device showed satisfactory efficacy in the screening of diabetic patients with or without diabetic retinopathy, being useful for places without infrastructure conditions.

Is there a relationship between the first-day results of anti-VEGF therapy for macular edema due to vascular diseases and longterm outcomes? / Há alguma relação entre os resultados do primeiro dia de terapia anti-VEGF para edema macular devido a doenças vasculares e o resultado a longo prazo?

ABSTRACT Purpose: To evaluate early changes after the first antivascular endothelial growth factor injection for macular edema secondary to diabetic retinopathy and retinal vein occlusion and the relationship between longterm outcomes. Methods: The study enrolled patients who received anti-vascular endothelial growth factor injections for treatment-naive macular edema due to retinal vein occlusion and diabetic retinopathy. The central macular thickness was measured at baseline, post-injection day 1, week 2, and month 1, and at the last visit using spectral-domain optical coherence tomography. A good response was defined as a central macular thickness reduction of ≥10% on post-injection day 1. Patients were reassessed at the last visit with regard to treatment response on post-injection day 1 based on the favorable anatomic outcome defined as a central macular thickness <350 µm. Results: In total, 26 (44.8%) patients had macular edema-retinal vein occlusion and 32 (55.2%) had macular edema-diabetic retinopathy. The mean follow-up time was 24.0 (SD 8.5) months. A statistically significant decrease in the central macular thickness was observed in both patients with macular edema-retinal vein occlusion and macular edema-diabetic retinopathy after antivascular endothelial growth factor injection therapy (p<0.001 for both). All patients with macular edema-retinal vein occlusion were good responders at post-injection day 1. All nongood responders at post-injection day 1 belong to the macular edema-diabetic retinopathy group (n=16.50%). The rate of hyperreflective spots was higher in nongood responders than in good responders of the macular edema-diabetic retinopathy group (p=0.03). Of 42 (2.4%) total good responders, one had a central macular thickness >350 µm, whereas 5 (31.2%) of 16 total nongood responders had a central macular thickness >350 µm at the last visit (p=0.003). Conclusion: The longterm anatomical outcomes of macular edema secondary to retinal vein occlusion and diabetic retinopathy may be predicted by treatment response 1 day after antivascular endothelial growth factor injection.

RESUMO Objetivo: Avaliar as alterações precoces após a primeira injeção de anticorpos antifator de crescimento endotelial vascular (anti-VEGF) em casos de edema macular secundário à retinopatia diabética e oclusão da veia da retina e a relação entre essas alterações e o resultado a longo prazo. Métodos: Foram incluídos no estudo pacientes que receberam uma injeção de antifator de crescimento endotelial vascular para edema macular, virgem de tratamento e devido à oclusão da veia retiniana ou a retinopatia diabética. A espessura macular central foi medida no início do tratamento e no 1º dia, 2ª semana e 1º mês após a injeção, bem como na última visita, através de tomografia de coerência óptica de domínio espectral. Definiu-se uma "boa resposta" como uma redução ≥10% na espessura macular central no 1º dia após a injeção. Os pacientes foram reavaliados na última visita com relação à resposta ao tratamento no 1º dia após a injeção, com base em um resultado anatômico favorável, definido como uma espessura macular central <350 µm. Resultado: Foram registrados 26 (44,8%) pacientes com edema macular e oclusão da veia da retina e 32 (55,2%) com edema macular e retinopatia diabética. O tempo médio de acompanhamento foi de 24,0 meses (desvio-padrão de 8,5 meses). Foi observada uma diminuição estatisticamente significativa da espessura macular central após o tratamento antifator de crescimento endotelial vascular tanto em pacientes com edema macular e oclusão da veia retiniana quanto naqueles com edema macular e retinopatia diabética (p<0,001 para ambos). Todos os pacientes com edema macular e oclusão da veia retiniana responderam bem no 1º dia pós-injeção. Todos os que responderam mal no 1º dia pós-injeção pertenciam ao grupo com edema macular e retinopatia diabética (n=16,50%). A presença de manchas hiperrefletivas foi maior nos pacientes que responderam mal do que naqueles que tiveram boa resposta no grupo com edema macular e retinopatia diabética (p=0,03). Um dos 42 (2,4%) pacientes com boa resposta total teve espessura macular central >350 um, enquanto 5 (31,2%) do total de 16 pacientes com resposta ruim apresentaram espessura macular central >350 µm na última visita (p=0,003). Conclusão: O resultado anatômico de longo prazo do edema macular secundário à oclusão da veia retiniana e à retinopatia diabética pode ser previsto pela resposta ao tratamento no 1º dia após a injeção de antifator de crescimento endotelial vascular.

Cilostazol protects against changes caused by streptozotocin-induced diabetic retinopathy / Cilostazol protege contra as alterações causadas pela retinopatia diabética induzida por estreptozotocina

ABSTRACT Purpose: This study investigates the protective effect of cilostazol on the development and evolution of diabetic retinopathy in rats. Methods: Sixty male rats were divided into four groups: untreated nondiabetic rats, untreated diabetic rats, cilostazol-treated nondiabetic rats, and cilostazol-treated diabetic rats. The thickness of the internal limiting membrane to the outer limiting membrane, inner plexiform layer, inner nuclear layer, and outer nuclear layer were measured. The number of cell nuclei per 50-μm length in retinal sections was counted to quantify the degree of retinal cell loss. Results: The number of nuclei in the ganglion cell layer was significantly higher in untreated nondiabetic rats (p<0.05). The mean number of nuclei in the cilostazol-treated nondiabetic rats was significantly higher than that in the cilostazol-treated diabetic rats (p<0.05). The cilostazol-treated nondiabetic rats had a significantly higher mean nuclei count in the inner nuclear layer and inner plexiform layer as compared with the other groups (p<0.05). The total mean retinal thickness of the cilostazol-treated nondiabetic rats was significantly higher than that of cilostazol-treated diabetic rats and untreated diabetic rats (p<0.05). Conclusion: By decreasing the loss of ganglion cells and reducing the sensorineural atrophy in the internal retinal layers, cilostazol had a protective effect against changes caused by diabetic retinopathy in diabetic rats.

RESUMO Objetivo: O objetivo deste estudo foi investigar o efeito protetor do cilostazol no desenvolvimento e na evolução da retinopatia diabética em ratos. Métodos: Sessenta ratos machos foram divididos em 4 grupos: ratos não-diabéticos não-tratados, ratos diabéticos não-tratados, ratos não-diabéticos tratados com cilostazol e ratos diabéticos tratados com cilostazol. A espessura da membrana limitante interna à membrana limitante externa, a camada plexiforme interna, a camada nuclear interna e a camada nuclear externa foram medidas. Para quantificar o grau de perda de células da retina, foi contado o número de núcleos de células por 50 μm de comprimento em secções retinianas. Resultados: O número de núcleos no GCL foi significativamente maior em Ratos não-diabéticos não-tratados com cilostazol (p<0,05). O número médio de núcleos em Ratos não-diabéticos tratados com cilostazol foi significativamente maior do que em Ratos diabéticos tratados com cilostazol (p<0,05). A contagem média de núcleos em camada nuclear interna e camada plexiforme interna de ratos não-diabéticos tratados com cilostazol foi significativamente maior do que nos outros grupos (p<0,05). A espessura retiniana média total de Ratos não-diabéticos tratados com cilostazol foi significativamente maior do que em Ratos diabéticos tratados com cilostazol e Ratos diabéticos não-tratados (p<0,05). Conclusão: Os resultados demonstraram que o cilostazol teve um efeito protetor contra as alterações causadas pela retinopatia diabética em ratos diabéticos, diminuindo a perda de células ganglionares e reduzindo a atrofia neurossensorial nas camadas retinianas internas.

Comparing the effects of serum GPER-1 and oxidant/antioxidant levels on retinopathy in patients with diabetes and healthy individuals: a pilot study / Comparando o impacto do soro GPER-1 e dos níveis de oxidante/antioxidante na retinopatia em pacientes diabéticos e em indivíduos saudáveis: um estudo piloto

ABSTRACT Purpose: This study aimed to determine the effect of serum G receptor-mediated protein-1 levels on the development of retinopathy in patients with diabetes in comparison with healthy individuals. Methods: The study enrolled patients with diabetic retinopathy (Group 1), patients without diabetic retinopathy (Group 2), and healthy individuals (Group 3). Levels of serum progesterone, serum G receptor-mediated protein-1, estradiol, oxidant/antioxidants, and thyroid-releasing hormones were analyzed and compared among the groups. Post-hoc analysis was performed to compare the subgroups in which significant differences were found. Results: Groups 1, 2, and 3 each included 40 patients. A significant difference was found among all groups in terms of serum G receptor-mediated protein-1, oxidant/antioxidant, and estradiol levels (p<0.01), but no significant difference was found in terms of thyroid-releasing hormone or progesterone (p=0.496, p=0.220, respectively). In the post-hoc analysis of the groups with significant differences, another significant difference was found among all groups for serum G receptor-mediated protein-1 and oxidant/antioxidant levels (p<0.05). Serum G receptor-mediated protein-1 and oxidant levels were positively correlated, whereas serum G receptor-mediated protein-1 and antioxidant levels were negatively correlated (r=0.622/p<0.01, r=0.453/p<0.01, r=0.460/p<0.01, respectively). The multiple regression analysis showed that increased levels of serum G receptor-mediated protein-1 may help prevent diabetic retinopathy. Conclusions: Serum G receptor-mediated protein-1 levels, which were the highest in the diabetic retinopathy Group, increased as the oxidant/antioxidant balance changed in favor of oxidative stress. This appears to be a defense mechanism for preventing neuronal damage.

RESUMO Objetivo: Esta pesquisa buscou determinar o im­pacto dos níveis de proteína G sérica no desenvolvimento da retinopatia em pacientes diabéticos, comparando-os a indivíduos saudáveis. Métodos: Foram incluídos, no estudo, 40 pacientes com retinopatia diabética (Grupo 1), 40 pacientes sem retinopatia diabética (Grupo 2) e 40 indivíduos saudáveis (Grupo 3). Os níveis hormonais de progesterona sérica, de proteína G sérica, estradiol, oxidante/antioxidante e hormônio liberado pela tireoide foram analisados e comparados. A análise post hoc foi realizada para comparar os subgrupos nos quais diferenças estatisticamente significativas foram encontradas. Resultados: Uma diferença significativa foi encontrada entre todos os grupos em termos de proteína G sérica, oxidante/antioxidante e níveis de estradiol (p<0.01), mas nenhuma diferença significativa foi encontrada em termos de hormônio liberado pela tireoide ou progesterona (p=0,496, p=0,220, respectivamente). Na análise post hoc dos grupos com diferenças estatisticamente significativas, outra diferença significativa foi encontrada entre todos os grupos para proteína G sérica e níveis oxidantes/antioxidantes (p<0,05). Os níveis de proteína G sérica e os níveis de oxidante foram positivamente correlacionados, enquanto os níveis de proteína G sérica e os níveis de antioxidantes foram negativamente correlacio­nados (r=0,622/p<0,01, r=0,453/p<0,01, r=0,460/p<0,01, respectivamente). A análise de regressão múltipla mos­trou que o aumento da proteína G sérica pode ajudar a prevenir a retinopatia diabética. Conclusões: Os níveis de proteína G sérica que eram mais altos no grupo de retinopatia diabética, aumentaram à medida que o equilíbrio oxidante/antioxidante mudou em favor do estresse oxidativo. Este parece ser um mecanismo de defesa para prevenir danos neuronais.