Macular dystrophies associated with Stargardt-like phenotypes / Distrofias maculares associadas a fenótipos Stargardt-like

ABSTRACT Purpose: Stargardt-like phenotype has been described as associated with pathogenic variants besides the ABCA4 gene. This study aimed to describe four cases with retinal appearance of Stargardt disease phenotypes and unexpected molecular findings. Methods: This report reviewed medical records of four patients with macular dystrophy and clinical features of Stargardt disease. Ophthalmic examination, fundus imaging, and next-generation sequencing were performed to evaluate pathogenic variants related to the phenotypes. Results: Patients presented macular atrophy and pigmentary changes suggesting Stargardt disease. The phenotypes of the two patients were associated with autosomal dominant inheritance pattern genes (RIMS1 and CRX) and in the other two patients were associated with recessive dominant inheritance pattern genes (CRB1 and RDH12) with variants predicted to be pathogenic. Conclusion: Macular dystrophies may have phenotypic similarities to Stargardt-like phenotype associated with other genes besides the classic ones.

RESUMO Objetivo: Fenótipos Stargardt-like já foram asso-ciados a variantes patogênicas no gene ABCA4. O propósito desse estudo é descrever quatro pacientes com achados retinianos semelhantes a doença de Stargardt com resultados moleculares diferentes do esperado. Métodos: Esse relato fez a revisão de prontuários médicos de quatro pacientes com distrofia macular e achados clínicos sugestivos de doença de Stargardt. Foram realizados avaliação oftalmológica, exames de imagens e testes usando next generation sequencing para avaliar variantes patogênicas associadas aos fenótipos dos pacientes. Resultados: Os pacientes apresentavam atrofia macular e alterações pigmentares sugerindo achados clínicos de doença de Stargardt. Dois pacientes foram associados a genes com herança autossômica dominante (RIMS1 e CRX) e dois pacientes foram associados a genes com herança autossômica recessiva (CRB1 e RDH12) com variantes preditoras de serem patogênicas. Conclusão: Distrofias maculares podem ter similaridades fenotípicas com fenótipo de Stargardt-like associados a outros genes além dos classicamente já descritos.

Antiangiogenic activity of photobiomodulation in experimental model using chorioallantoic embryonic membrane of chicken eggs / Atividade antiangiogênica da fotobiomodulação em modelo experimental usando membrana embrionária corioalantóide de ovos de galinhas

ABSTRACT Purpose: The purpose of this study was to investigate the vascular effects of photobiomodulation using a light-emitting diode on the chorioallantoic embryonic membrane of chicken eggs grouped into different times of exposure and to detect the morphological changes induced by the light on the vascular network architecture using quantitative metrics. Methods: We used a phototherapy device with light-emitting diode (670 nm wavelength) as the source of photobiomodulation. We applied the red light at a distance of 2.5 cm to the surface of the chorioallantoic embryonic membrane of chicken eggs in 2, 4, or 8 sessions for 90 s and analyzed the vascular network architecture using AngioTool software (National Cancer Institute, USA). We treated the negative control group with 50 μl phosphate-buffered-saline (pH 7.4) and the positive control group (Beva) with 50 μl bevacizumab solution (Avastin, Produtos Roche Químicos e Farmacêuticos, S.A., Brazil). Results: We found a decrease in total vessel length in the Beva group (24.96% ± 12.85%) and in all the groups that received 670 nm red light therapy (2× group, 34.66% ± 8.66%; 4× group, 42.42% ± 5.26%; 8× group, 38.48% ± 6.96%), compared with the negative control group. The fluence of 5.4 J/cm2 in 4 sessions (4×) showed more regular vessels. The number of junctions in the groups that received a higher incidence of 670 nm red light (4× and 8×) significantly decreased (p<0.0001). Conclusion: Photo-biomodulation helps reduce vascularization in chorioallantoic embryonic membrane of chicken eggs and changes in the network architecture. Our results open the possibility of future clinical studies on using this therapy in patients with retinal diseases with neovascular components, especially age-related macular degeneration.

RESUMO Objetivo: investigar os efeitos vasculares da foto-biomodulação com diodo emissor de luz utilizando membrana embrionária corioalantóide de ovos de galinhas em grupos com diferentes tempos de exposição e detectar as alterações morfológicas por meio de métricas quantitativas promovidas pela luz na arquitetura da rede vascular. Métodos: Um aparelho de fototerapia com diodo emissor de luz no comprimento de onda de 670 nm foi usado como fonte de fotobiomodulação. A luz vermelha foi aplicada a uma distância de 2,5 cm da superfície da membrana embrionária corioalantóide em 2, 4 ou 8 sessões de 90 s a arquitetura da rede vascular foi analisada por meio do software AngioTool (National Cancer Institute, USA). Usamos um grupo controle negativo tratado com 50 µL de solução salina tamponada com fosfato (PBS) pH 7,4 e um grupo controle positivo (Beva) tratado com 50 µL de solução de bevacizumabe (Avastin, Produtos Roche Químicos e Farmacêuticos S.A., Brasil). Resultados: Uma diminuição no comprimento total do vaso foi detectada para o grupo Beva (24,96 ± 12,85%), e para todos os grupos que receberam terapia de luz vermelha de 670 nm, 34,66 ± 8,66% (2x), 42,42 ± 5,26% (4x) e 38,48 ± 6,96% (8x) em comparação ao grupo controle. A incidência de 5,4 J/cm2 em 4 sessões (4x) mostrou vasos mais regulares. A redução foi mais intensa nos grupos que receberam maior incidência de luz vermelha de 670 nm (4x e 8x). Conclusão: A fotobiomodulação contribui para a redução da vascularização nos vasos da membrana embrionária corioalantóide de ovos de galinhas e mudanças na arquitetura da rede. Os achados deste experimento abrem a possibilidade de considerar um estudo clínico usando esta terapia em pacientes com doenças retinais com componentes neovasculares, especialmente degeneração macular relacionada à idade.

PRPH2 mutation c.582-1G>A causing adult-onset macular dystrophy with a benign concentric annular macular dystrophy phenotype in a family / Mutação c.582-1G>A do gene PRPH2 causando distrofia macular de início adulto com fenótipo de distrofia macular anular concêntrica benigna em uma família

ABSTRACT The peripherin gene (PRPH2) mutation is associated with photoreceptor cell dysfunction as well as in several inherited retinal dystrophies. The PRPH2 mutation c.582-1G>A is a rare variant reported in retinitis pigmentosa and pattern dystrophy. Here Case 1 was of a 54-year-old woman with bilateral atrophy of the perifoveal retinal pigmentary epithelium and choriocapillaris with central foveolar respect. Autofluorescence and fluorescein angiography revealed perifoveal atrophy of the retinal pigmentary epithelium with an annular window effect without the "dark choroid" sign. Case 2 (mother of Case 1) presented with extensive atrophy of the retinal pigmentary epithelium and choriocapillaris. PRPH2 was evaluated and the c.582-1G>A mutation was identified in heterozygosity. An advanced adult-onset benign concentric annular macular dystrophy diagnosis was thereby proposed. The c.582-1G>A mutation is poorly known and not present in all common genomic databases. This case report is the first one to report a c.582-1G>A mutation associated with benign concentric annular macular dystrophy.

RESUMO Mutações do gene da periferina (PRPH2) estão associadas à disfunção das células fotorreceptoras e estão envolvidas em várias distrofias retinianas hereditárias. A mutação c.582-1G>A do gene PRPH2 é uma variante rara, relatada na retinite pigmentosa e nas distrofias em padrão. O caso 1 foi de uma mulher de 54 anos com atrofia bilateral do epitélio pigmentar da retina perifoveal e da coriocapilar, com acometimento foveolar central. A autofluorescência e a angiofluoresceinografia revelaram atrofia perifoveal do epitélio pigmentar da retina, com efeito de janela anular, sem o sinal da "coroide escura". O caso 2 (mãe) apresentava extensa atrofia do epitélio pigmentar da retina e da coriocapilar. Foi feito um estudo do gene PRPH2, que identificou a mutação c.582-1G>A em heterozigose. Foi proposto um diagnóstico de distrofia macular anular concêntrica benigna de início adulto em estágio avançado. A mutação c.582-1G>A é pouco conhecida e não está presente em todos os bancos de dados genômicos usuais. Este é o primeiro relato de caso publicado de uma mutação c.582-1G>A associada à distrofia macular anular concêntrica benigna.

Efficacy of low-vision devices in elderly population with age-related macular degeneration

Purpose: Age?related macular degeneration (AMD) is a common cause of blindness, residual damage to macular area in spite of treatment necessitates visual rehabilitation by means of low?vision aids (LVAs). Methods: Thirty patients suffering from different stages of AMD requiring LVAs were included in this prospective study. Patients with nonprogressive, adequately treated AMD were enrolled over a 12?month period, prescribed requisite LVAs and followed?up for a minimum 1?month period. Before and after provision of LVAs, near work efficiencies were evaluated by calculating reading speed as words per minute (wpm) under both photopic and mesopic light conditions, and impact of poor vision on activities of daily living (ADL) was quantified by modified standard questionnaire based on Nhung X et al. questionnaire. Results: Of the 30 patients mean studied with mean age of 68 ± 10 years, 20 patients (66.7%) had dry AMD in better eye and 10 (33.3%) had wet AMD. Post?LVA, near visual acuity improved significantly and all cases were able to read some letters on near vision chart with an average improvement of 2.4 ± 0.96 lines. The different LVAs prescribed were high plus reading spectacles (up to 10 D) in 23.3%, hand?held magnifiers in 53.3%, base in prisms in 10%, stand held magnifiers in 6.7%, and bar and dome magnifiers in 3.3%. Conclusion: LVAs are effective in visual rehabilitation in patients with AMD. Self?reported reduction in visual dependency and improvement in vision?related quality of life post use of aids corroborated perceived benefit.

Desprendimiento de la capa bacilar de la retina asociado a enfermedad inflamatoria ocular

El desprendimiento de la capa bacilar de la retina es la separación de los segmentos internos de los fotorreceptores del resto de la retina neurosensorial, o separación entre la zona miode y elipsoide de la retina, que en un hallazgo reciente se puede identificar mediante la tomografía de coherencia óptica de dominio espectral. El objetivo es actualizar los conocimientos sobre el desprendimiento de la capa bacilar de la retina y el uso de la tomografía de coherencia óptica de dominio espectral en las enfermedades oculares que están asociadas con este signo. Se consultaron las fuentes bibliográficas como Google académico, SciELO LAC, Medline y MEDICARIBE. Se limitaron los resultados al idioma español e inglés y a los últimos cinco años. Se recuperaron 54 documentos, de ellos 18 resultaron relevantes a esta investigación. Los autores más mencionados fueron Ramtohul, Metha y Cicinelli. Ellos trabajaron el signo clínico en cuestión y reportaron la experiencia en la atención a los pacientes aquejados con esta enfermedad ocular. El desprendimiento de la capa bacilar de la retina es un signo presente en varias enfermedades asociadas a inflamación del segmento posterior ocular. La tomografía de coherencia óptica de dominio espectral es una técnica efectiva para determinarlo, aunque estos planteamientos aún son escasos en la literatura, lo cual reafirma la importancia científica de continuar los estudios a partir de hipótesis iniciales desde el punto de vista histológico y tomográfico.

Retinal bacillary layer detachment is the separation of the inner segments of the photoreceptors from the rest of the neurosensory retina, or separation between the myode and ellipsoid zone of the retina, which in a recent finding can be identified by spectral-domain optical coherence tomography. The objective is to update the knowledge about the detachment of the bacillary layer of the retina and the use of spectral-domain optical coherence tomography in ocular diseases that are associated with this sign. Bibliographic sources such as academic Google, SciELO LAC, MEDLINE and MEDICARIBE were consulted. Fifty-four documents were retrieved, of which 18 were relevant to this research. The results were limited to the Spanish and English language and to the last five years. The most mentioned authors were Ramtohul, Metha and Cicinelli. They worked on the clinical sign in question and reported the experience in caring for patients afflicted with this ocular disease. Detachment of the bacillary layer of the retina is a sign present in several diseases associated with ocular posterior segment inflammation. Spectral-domain optical coherence tomography is an effective technique to determine it, although it is still scarce in the literature, which reaffirms the scientific validity of continuing studies from initial hypotheses from the histological and tomographic point of view.

The Clinical Outcome of Brolucizumab in the Treatment of Neovascular Age-Related Macular Degeneration – A Prospective Observational Study

Background: Neovascular age-related macular degeneration (nAMD), also known as wet AMD, is a chronic eye disease that affects the macula, which is the central part of the retina responsible for sharp, central vision. Brolucizumab is a type of anti-vascular endothelial growth factor (VEGF) drug, which works by blocking the activity of a protein called VEGF that promotes the growth of abnormal blood vessels under the macula in neovascular AMD. The aim of this study was to evaluate the clinical outcome of brolucizumab in the treatment of neovascular age-related macular degeneration. Material & Methods: This prospective observational study was conducted in Department of Ophthalmology, Bangladesh Eye Hospital & Institute Ltd, Dhaka, Bangladesh, during the period from February 2022 to February 2023. Total 60 patients with neovascular AMD were included in this study who were treated with brolucizumab. Results: The mean age of the patients was 74.3 (SD±9.8) years. Majority of the study subjects were (51.7%) female patients in the study. In our study, majority (38.3%) of the patients had only their right eye affected. In optical coherence tomography (OCT) findings, we found that a high percentage of patients had subretinal fluid (85%), intraretinal fluid (61.7%), and sub-RPE fluid (83.3%). The BCVA showed a significant change after 12 weeks of treatment, as indicated by the P-value of 0.0007. Here improvement of vision was seen in patients with AMD with active Choroidal neovascularization (CNV). But in case of AMD with macular scar, no improvement of vision was seen. In addition, the SRT, FCP, and CMT parameters also showed a statistically significant (P<0.001) improvement after brolucizumab treatment. In our study, 4 patients (6.7%) experienced intraocular inflammation, which is inflammation within the eye, 2 patients (3.3%) reported cloudy vision, and 3 patients (5%) experienced eye redness as a complication of the treatment. The majority of the patients, 51 (85%) did not experience any complications from the treatment. After treatment, improved vision was seen in most of the study patients (70%) and 30% had no improvement. Conclusion: From the findings of our study, it can be concluded that brolucizumab may be an effective treatment for neovascular AMD, as it can improve the best-corrected visual acuity and structural outcomes of the retina such as subfoveal retinal thickness, foveal center point, and central macular thickness. There was also a tolerable complication rate after treatment.

The nuclear factor E2-related factor 2 and age-related macular degeneration / O fator 2 relacionado a NF-E2 e a degeneração macular relacionada à idade

ABSTRACT After the discovery of anti-vascular endothelial growth factor agents as treatment of wet age-related macular degeneration, the number of studies with the objective to understand the molecular mechanisms involved in the age-re lated macular degeneration genesis has increased. The importance of the nuclear factor e2-related factor 2 lies in its activation-derived proteins being involved in the maintenance of the redox balance and consequent prevention of degenerative macular disease. This article aims to present the characteristics of nuclear factor e2-related factor 2 and describe the main nuclear factor e2-related factor 2-activated antioxidant enzymes that contribute to the preservation of vision.

RESUMO Após a descoberta do anti fator de crescimento en dotelial vascular no tratamento da degeneração macular relacionada à idade úmida, muitas pesquisas têm sido realizadas com o intuito de elucidar os mecanismos moleculares envolvidos na gênese da degeneração macular relacionada à idade. O fator nuclear eritroide 2 relacionado ao fator 2 destaca-se pelo fato de diversas proteínas, oriundas de sua ativação, estarem envolvidas na manutenção do equilíbrio do estado redox e consequente prevenção da doença macular degenerativa. Este artigo mostra as características do fator nuclear eritroide 2 relacionado ao fator 2 e descreve as principais enzimas antioxidantes originadas da ativação que contribuem para a preservação da visão.

Baseline predictors of short-term visual outcomes after intravitreal conbercept injection for neovascular age-related macular degeneration / Preditores iniciais de desfechos visuais de curto prazo com injeção intravítrea de combercepte para degeneração macular neovascular relacionada à idade

ABSTRACT Purpose: Neovascular age-related macular degeneration is the leading cause of vision loss in the elderly. We aimed to identify baseline predictors of visual prognosis after intravitreal conbercept injection for neovascular age-related macular degeneration. Methods: We conducted a retrospective review of 58 patients with neovascular age-related macular degeneration who were treated with intravitreal injections of conbercept 0.5 mg in routine clinical practice. Basic information such as age, sex, intraocular pressure, and disease course was collected. Best-corrected visual acuity, mean retinal sensitivity, and optical coherence tomography findings were recorded at baseline and 6 months after treatment. Logistic regression analysis was used to identify independent predictors of best-corrected visual acuity at 6 months after treatment. Results: After the 6-month treatment, the mean best-corrected visual acuity improved from 1.10 ± 0.42 logarithm of the minimum angle of resolution (logMAR) to 0.41 ± 0.18 logMAR, the mean retinal sensitivity increased from 5.13 ± 0.86 dB to 7.32 ± 1.21 dB, the mean central retinal thickness decreased from 440.38 ± 61.05 μm to 260.01 ± 24.86 μm, and the total number of hyperreflective dots and the number of hyperreflective dots in each retina layer were significantly reduced as compared with those before treatment (all p<0.05). Twenty-two patients showed improved vision, and 36 had unimproved vision. Multivariate analyses revealed that the number of subretinal hyperreflective dots, the state of external limiting membrane, baseline best-corrected visual acuity, and age were independent predictors of best-corrected visual acuity (all p<0.05). Conclusion: Poor recovery of patients after intravitreal conbercept injection may be related to the number of subretinal hyperreflective dots, the state of external limiting membrane, baseline best-corrected visual acuity, and age, which may be used as predictors of short-term visual outcomes and should be fully evaluated before operation.

RESUMO Objetivo: A degeneração macular neovascular relacionada à idade é a principal causa de perda de visão em idosos. O objetivo deste estudo foi identificar os preditores iniciais que afetam o prognóstico visual após a injeção intravítrea de combercepte para degeneração macular neovascular relacionada à idade. Métodos: Esta é uma revisão retrospectiva de 58 pacientes com degeneração macular neovascular relacionada à idade que foram tratados com injeções intravítreas de 0,5 mg de combercepte na prática clínica de rotina. Foram coletadas informações básicas, tais como idade, sexo, pressão intraocular e evolução da doença. A melhor acuidade visual corrigida, as sensibilidades retinianas médias e varreduras de tomografia de coerência óptica foram registradas no início do estudo e 6 meses após o tratamento. Foi efetuada uma análise de regressão logística para determinar os preditores independentes da melhor acuidade visual corrigida 6 meses após o tratamento. Resultados: Após 6 meses de tratamento, a média da acuidade visual melhor corrigida melhorou de 1,10 ± 0,42 para 0,41 ± 0,18 logMAR; as sensibilidades retinianas médias aumentaram de 5,13 ± 0,86 para 7,32 ± 1,21 dB; a espessura retiniana central média diminuiu de 440,38 ± 61,05 para 260,01 ± 24,86 μm; e os pontos hiper-reflexivos, tanto em números totais quanto em cada camada de retina, foram significativamente reduzidos em comparação com os valores de antes do tratamento (todos com p<0,05). Houve 22 pacientes com visão melhorada e 36 pacientes com visão não melhorada. As análises multivariadas mostraram que o número de pontos hiper-reflexivos sub-retinianos, o estado da membrana limitante externa, a melhor acuidade visual corrigida inicial e a idade foram preditores independentes para a melhor acuidade visual corrigida (todos com p<0,05). Conclusão: A má recuperação de pacientes após a injeção de combercepte intravítreo pode estar relacionada ao número de pontos hiper-reflexivos sub-retinianos, ao estado da membrana limitante externa, à acuidade visual corrigida inicial e à idade, parâmetros que podem ser usados como preditores de resultados visuais de curto prazo e devem ser totalmente avaliados antes da cirurgia.

Perfil epidemiológico de pacientes com degeneração macular relacionada à idade / Epidemiological profile of patients with age-related macular degeneration

RESUMO Objetivo Demonstrar o perfil epidemiológico e fatores de riscos de pacientes com degeneração macular relacionada à idade. Métodos Estudo observacional e seccional. Foi incluído um olho de cada paciente com maior comprometimento visual por degeneração macular relacionada à idade atendido no Hospital Universitário Antônio Pedro. A variável principal a ser comparada foi a presença de degeneração macular relacionada à idade dividida nos estágios inexpressivo, inicial, intermediário e avançado, segundo classificação do estudo AREDS. As variáveis secundárias foram os dados demográficos (sexo, idade, raça, faixa etária), índice de massa corporal, cor da íris, história familiar de degeneração macular relacionada à idade, status do cristalino, longo tempo exposição à luz ultravioleta e tabagismo. Foram realizados testes estatísticos com análise de Kruskal-Wallis, do teste do qui-quadrado e teste t de Student. O nível de significância foi definido em 5%. Resultados Após os critérios de inclusão e exclusão, 126 pacientes foram incluídos neste estudo, sendo 20 pacientes com degeneração macular relacionada à idade inexpressiva, 30 pacientes com degeneração macular relacionada à idade inicial, 30 pacientes com degeneração macular relacionada à idade intermediária e 46 pacientes com degeneração macular relacionada à idade avançada. Dentre todos os fatores de risco pesquisados, apenas o tabagismo se mostrou estatisticamente significativo (p=0,03). Conclusão O tabagismo como fator de risco para degeneração macular relacionada à idade apresentou ter importância expressiva prevalente nesta pesquisa e até mesmo como fator preventivo dessa morbidade ocular.

ABSTRACT Purpose To demonstrate the epidemiological profile and risk factors of patients with age-related macular degeneration (ARMD). Methods Observational and sectional study. One eye of each patient with greater visual impairment due to AMD treated at the University Hospital Antônio Pedro was included. The main variable to be compared was the presence of AMD divided into inexpressive, initial, intermediate, and advanced stages, according to the classification of the AREDS study. The secondary variables were demographics (gender, age, race, age group), body mass index, iris color, family history of ARMD, lens status, long-term exposure to ultraviolet light and smoking. Statistical tests were performed with Kruskal-Wallis and Chi-square analyses and Student's t test. The significance level was set at 5%. Results After the inclusion and exclusion criteria, 126 patients were included in this study, 20 patients with non-expressive AMD, 30 patients with early AMD, 30 patients with intermediate AMD, and 46 patients with advanced AMD. Among all the risk factors surveyed, only smoking was statistically significant (p = 0.03). Conclusion Smoking as a risk factor for AMD had significant relevance prevalent in this research and even as a preventive factor for this ocular morbidity.

Comparing six cases of external macular holes and literature review / Comparação de seis casos de buracos maculares externos e revisão de literatura

ABSTRACT The characteristic optical coherence tomography finding in solar maculopathy is a well-defined outer retinal hyporeflective space primarily involving the photoreceptor inner and outer segment layers. This typical optical coherence tomography image may be present in a few other pathologies, which currently constitute their main differential diagnoses. Our study shows the report of 12 eyes of 6 patients treated at the Hospital de Olhos do Paraná, presenting their clinical history and diagnostic images, with the purpose of comparing the findings of the first 3 patients (diagnosed with solar maculopathy) with the last 3 patients, which are also cases of external macular holes.

RESUMO O achado característico da tomografia de coerência óptica na maculopatia solar é um espaço hiporrefletivo retiniano externo bem definido, envolvendo principalmente as camadas dos segmentos interno e externo dos fotorreceptores. Essa imagem típica da tomografia de coerência óptica pode estar presente em algumas outras patologias, que atualmente constituem seus principais diagnósticos diferenciais. Nosso estudo mostra o relato de 12 olhos de 6 pacientes atendidos no Hospital de Olhos do Paraná, apresentando sua história clínica e imagens diagnósticas, com o objetivo de comparar os achados dos 3 primeiros pacientes (diagnosticados com maculopatia solar) com os 3 últimos pacientes, que também são casos de buracos maculares externos.

Stem cell therapy in stargardt disease: a systematic review

This article aimed to review current literature on the safety and efficacy of stem cell therapy in Stargardt disease. A comprehensive literature search was performed, and two animal and eleven human clinical trials were retrieved. These studies utilized different kinds of stem cells, including human or mouse embryonic stem cells, mesenchymal stem cells, bone marrow mononuclear fraction, and autologous bone marrow-derived stem cells. In addition, different injection techniques including subretinal, intravitreal, and suprachoroidal space injections have been evaluated. Although stem cell therapy holds promise in improving visual function in patients with Stargardt disease, further investigation is needed to determine the long-term benefits, safety, and efficacy in determining the best delivery method and selecting the most appropriate stem cell type.

Analysis of the epidemiological burden of age-related macular degeneration in China based on the data of global burden of disease / 中南大学学报(医学版)

OBJECTIVES@#Age-related macular degeneration (AMD) is one of the 3 major eye diseases recognized by WHO to prevent blindness, and which is the main cause of irreversible visual impairment in the elderly. This study aims to analyze the disease epidemiological burden, and provide a theoretical foundation for the prevention and control of AMD in China based on the data in global burden of disease (GBD) 2019.@*METHODS@#The prevalent cases/prevalence, disability-adjusted life year (DALYs)/DALY rate of AMD and socio-demographic index (SDI) for global and China were searched from the GBD 2019 database to analyze the epidemiological trend, age-period-gender trend of AMD in China from 1990 to 2019, and to evaluate the relations between the prevalence and SDI.@*RESULTS@#In 2019, the prevalence of AMD in China was at a high level in the world, and the number of prevalent cases were 1.93 times of that in 1990. The prevalence and DALY rates continued to rise. The age trend of AMD in China was high at the middle of the age stages and low at the two ends, and which was higher in the female than in the male. With the increase of SDI, the prevalence of AMD was increased linearly.@*CONCLUSIONS@#The disease burden of AMD in China is increased significantly and is positively correlated with the social development from 1990 to 2019. It is of great significance to study the relationship between epidemilolgical data of AMD and social development level for diagnosis treatment and policy of AMD.

Expression levels of serum miR-126 and miR-9 in patients with wet age-related macular degeneration and their relationship with VEGF and CMT / 中国医师杂志

Objective:To investigate the expression levels of serum miR-126 and miR-9 in patients with wet age-related macular degeneration (wAMD) and their relationship with vascular endothelial growth factor (VEGF) and central macular thickness (CMT).Methods:A total of 73 wAMD patients(observation group) admitted to the ophthalmology department of Taizhou Municipal Hospital from May 2020 to May 2021 and 60 healthy subjects (control group) who underwent physical examination during the same period were selected. Real-time quantitative polymerase chain reaction (qRT-PCR) was used to detect the expression levels of miR-126 and miR-9 in serum of the two groups. Serum angiogenesis regulatory factors [VEGF, tissue inhibitor of melalloproteinuses-1 (TIMP-1), endostatin (ES), platelet-derived growth factor (PDGF)] were detected by enzyme-linked immunosorbent assay (ELISA), and CMT and intraocular pressure (IOP) were measured. Pearson correlation analysis was performed to determine the correlation between miR-126 and miR-9 and serum angiogenesis regulatory factor levels, CMT and IOP. The diagnostic value of miR-126 and miR-9 in wAMD was analyzed by receiver operating characteristic (ROC) curve.Results:The relative expression level of serum miR-126 in observation group was significantly lower than that in control group ( P<0.05) , while the relative expression level of serum miR-9 was significantly higher than that in control group ( P<0.05). The levels of serum VEGF and PDGF in observation group were significantly higher than those in control group (all P<0.05), while the levels of serum TIMP-1 and ES were significantly lower than those in control group (all P<0.05). CMT and IOP in observation group were significantly higher than those in control group (all P<0.05). The expression level of serum miR-126 in observation group was negatively correlated with serum VEGF, PDGF, CMT and IOP ( r=-0.275, -0.523, -0.302, -0.542, all P<0.05), and was positively correlated with TIMP-1 and ES ( r=0.460, 0.263, all P<0.05). Serum miR-9 expression level was positively correlated with serum VEGF, PDGF, CMT and IOP ( r=0.434, 0.438, 0.396, 0.307, all P<0.05), and was negatively correlated with TIMP-1 and ES ( r=-0.256, -0.310, all P<0.05). The area under curve (AUC) values of serum miR-126 and miR-9 in diagnosing wAMD were 0.713 and 0.847 respectively. Conclusions:The expression level of serum miR-126 is significantly decreased while the expression level of miR-9 is significantly increased in patients with wAMD. miR-126 is negatively correlated with VEGF and CMT, and miR-9 is positively correlated with VEGF and CMT, which may aggravate the disease by promoting the inflammatory response. The detection of expression levels of serum miR-126 and miR-9 is helpful to provide the reference basis for early diagnosis of wAMD and early prevention and treatment.

The role of NLRP3/GATA-4/VEGF signal pathway in neovascular age-related macular degeneration / 中国医师杂志

Objective:To explore the potential role of nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3)/GATA-binding protein 4 (GATA-4)/vascular endothelial growth factor (VEGF) signal pathway in neovascular age-related macular degeneration (nAMD).Methods:We applied the TRANSFAC Public database to search the human and mouse VEGF promoters and upstream transcription factors, analyzed the transcription factors that may influence the transcriptional activity of VEGF. The RAW264.7 cells were divided into control group and lipopolysaccharide (LPS) stimulated group (LPS group). Real time fluorescence quantitative polymerase chain reaction (qRT-PCR) was used to detect the activation of NLRP3 inflammasome, and the mRNA levels of GATA-4 and VEGFA. Thus, we applied the specific small molecular NLRP3 inhibitor MCC950 pretreated RAW264.7 cells (LPS+ MCC950 group), and detected the gene expression of NLRP3, Caspase-1, interleukin 1β( IL-1β), GATA-4 and VEGFA.Results:There were multiple GATA transcription factor binding sites upstream of human and mouse VEGF promoters. Compared with the control group, mRNA expression of NLRP3, Caspase-1, IL-1β, GATA-4 and VEGFA in LPS group were increased (all P<0.05). Compared with LPS group, mRNA expression of NLRP3, Caspase-1, IL-1β, GATA-4 and VEGFA in LPS+ MCC950 group were significantly decreased (all P<0.05). Conclusions:NLRP3/GATA-4/VEGF signal pathway may play a significant role in the pathologic processes of nAMD.

Influencing factors of poor response to anti-vascular endothelial growth factor drug therapy for wet age-related macular degeneration and therapeutic strategy of targeting pericytes / 国际眼科杂志(Guoji Yanke Zazhi)

With the increasing aging population, the incidence of wet age-related macular degeneration(wARMD)is gradually rising. The formation of neovascularization leads to recurrent hemorrhage in the macular region, which is one of the main causes of blindness in the elderly. Currently, the primary clinical treatment for wARMD is intravitreal injection of anti-vascular endothelial growth factor(VEGF)drugs. However, there are still some patients who have poor or no response to anti-VEGF drugs, resulting in suboptimal or ineffective clinical outcomes. Analyzing the specific influencing factors will be beneficial in guiding clinical decision-making. This article reviews the impact of factors such as advanced age, treatment duration, number of injections, characteristics of neovascular lesions, macular structure, intraocular cytokine levels, and genetics on the response to anti-VEGF therapy. In addition, recent studies have found that pericytes, as cellular components of microvascular walls, can influence the sensitivity to anti-VEGF therapy. This review summarizes the current research on the mechanisms of pericytes in poor or non-response to anti-VEGF therapy and discusses targeted strategies focusing on pericytes.

Research progress of medication treatment of dry age-related macular degeneration / 国际眼科杂志(Guoji Yanke Zazhi)

Age-related macular degeneration(ARMD)is one of the leading causes of irreversible visual impairment worldwide, and the number of patients is increasing with the aging of the population, with dry ARMD accounting for about 90% of cases. Effective treatments for dry ARMD are currently lacking, making it a prominent area of research. Pharmacotherapy, targeting pathogenic factors such as oxidative damage, inflammation, and vascular issues contributing to ARMD, is one of the main treatments and some drugs have been shown to slow the progression of ARMD. This article reviews drug treatments for dry ARMD, including antioxidant drugs, complement biological agents, non-steroidal anti-inflammatory drugs and immunosuppressants, vasodilators, neurotrophic drugs, as well as traditional Chinese medicine. It summarizes their mechanisms and recent clinical research to contribute valuable insights for the treatment of dry ARMD and the development of novel therapeutic agents.

Research progress of microfluidic chips in age-related macular degeneration / 国际眼科杂志(Guoji Yanke Zazhi)

Age-related macular degeneration(ARMD)is the primary cause of severe visual impairment and blindness in people over 60 years old. With the aging of the global population, the incidence of the disease is also rising year by year. However, the pathogenesis and treatment strategy of ARMD need to be further explored. As a cutting-edge science and technology, microfluidic chips can build a comprehensive microsystem that simulates the condition and function of human tissues and organs, which has the advantages of less sample consumption and short analysis time. In recent years, many studies have confirmed that microfluidic chips can bring brand new technology solutions to the basic and clinical research of ARMD. This article will discuss and review the application progress of microfluidic chips in the areas of ARMD mechanism research, drug evaluation and clinical translation, providing a theoretical reference for further research on the diagnosis and treatment of ARMD.

Strong Linkage Disequilibrium and Haplotype Association of Neovascular Age-related Macular Degeneration in Indonesian Patients

@#Introduction: The aim of this study was to investigate the linkage disequilibrium (LD) and haplotype of three most associated SNP with nAMD of 80 patients in Indonesia. Methods: All patients underwent standard ophthalmic tests including fundoscopy and optical coherence tomography. Genomic DNA was extracted using commercially available DNA isolation kits. Genotyping of rs11200638, rs1061170 and del443ins54 used polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) methods. The acquired genotype data were analyzed using Haploview and R package software. Results: Linkage Disequilibrium analyses showed high LD value in the 10q26 region of 80 patients with AMD and 85 controls. The PCR-RFLP showed TTA was the most frequent haplotype while GTG was the most associated haplotype in the study sample. Conclusion: There was a high LD in the 10q26 region and strong association in GTG haplotype of Indonesian patients with AMD.

An update on anti-vascular endothelial growth factor therapy in retinal diseases / 中华眼底病杂志

Vascular endothelial growth factor (VEGF) is a multifunctional factor that promotes blood vessel formation and increases vascular permeability. Its abnormal elevation plays a key role in common retinal diseases such as wet age-related macular degeneration and diabetic macular edema. Anti-VEGF therapy can inhibit angiogenesis, reduce vascular leakage and edema, thereby delaying disease progression and stabilizing or improving vision. Currently, the clinical application of anti-VEGF drugs has achieved satisfactory therapeutic effects, but there are also issues such as high injection frequency, heavy economy burden, potential systemic side effects, and non-responsiveness. To address these issues, current research and development mainly aim on biosimilars, multi-target drugs, drug delivery systems, oral anti-VEGF drugs, and gene therapy. Some drugs have shown great potential and are expected to turn over a new leaf for anti-VEGF treatment in ophthalmology.

Clinical features of acute macular neuroretinopathy induced by Omicron / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To observe the clinical features of acute macular neuroretinopathy(AMN)induced by Omicron.METHODS: A retrospective study. A total of 9 patients(18 eyes)diagnosed with AMN from December 2022 to January 2023 in the Hospital of Chengdu University of Traditional Chinese Medicine were included. Patients underwent spectral-domain optical coherence tomography(SD-OCT), fundus fluorescein angiography(FFA), fundus photography, autofluorescence(AF), infrared reflectance(IR), optical coherence tomography angiography(OCTA)and multicolor, etc. Furthermore, they were followed up for 1～3mo and observed the prognosis.RESULTS: The initial symptom of the Omicron-induced AMN was the sudden onset of central/paracentral scotoma in the eyes with or without impaired vision and metamorphopsia, and the scotoma could persist for at least 3mo. The image features of AMN are as follows. First, the SD-OCT examination showed the rupture of outer retinal layers, scattered hyperreflective lesions, and atrophy of outer retinal layers. In severe cases, hyperreflective lesions were seen in the inner nuclear layer(INL)or with microcystic cavities under the retinal pigment epithelium(RPE). Second, the OCTA examination demonstrated the decreased blood flow density of the deep capillary plexus(DCP)of the macula. Third, the IR examination showed the weak reflection of lesion areas. Fourth, the fundus photography demonstrated the localized brown wedge-shaped lesion.CONCLUSIONS: The Omicron-induced AMN is mostly found in young females, and the characteristic manifestation of fundus is damage to the outer retinal layers. The extent of fundus lesions is related to the systemic inflammatory response and ocular microcirculatory changes after infection. The multimodal fundus image examination and a history of Omicron infection are helpful to diagnose the Omicron-induced AMN.