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.

Research progress of Charles Bonnet syndrome / 国际眼科杂志(Guoji Yanke Zazhi)

Charles Bonnet syndrome(CBS)refers to hallucinations resulting from visual pathway damage in individuals without neuropsychiatric disorders. CBS patients typically have insight into the unreality of their hallucinations, and the disorder may be episodic, periodic, or chronic. The condition's prevalence varies from 0.4% to 30% due to the absence of agreed diagnostic criteria for CBS and some patients' reluctance to acknowledge hallucinations. Massive studies have demonstrated an association between CBS and ocular diseases, such as age-related macular degeneration and glaucoma. Additionally, there have been reports of CBS occurring after ophthalmic surgery or medication. Therefore, clinicians should be vigilant in diagnosing CBS promptly and reassuring patients. There is a lack of literature on CBS in ophthalmology, and further research is needed to explore its pathogenesis and diagnostic and therapeutic options. This article reviews some of the studies related to CBS in recent years.

Mongolian medicine Mingmu-11 Pills combined with Conbercept in the treatment of wet age-related macular degeneration / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To evaluate the clinical efficacy of Mongolian medicine Mingmu-11 Pills combined with conbercept in the treatment of wet age-related macular degeneration(wARMD).METHODS: Prospective study. All cases in this study were wARMD patients(72 cases, 72 eyes)admitted to the Ophthalmology Department of Affiliated Hospital of Inner Mongolia University from November 2020 to December 2021. They were randomly divided into a combined treatment group and a control group, each with 36 eyes, and the control group received intravitreal injection of conbercept 0.05 mL for 3 consecutive months. The combined treatment group was given Mingmu-11 Pills twice a day after surgery, with 3 wk as a course of treatment, a total of 3 courses, and the control group was not given Mongolian medicine treatment. The best corrected visual acuity(BCVA), changes in central macular thickness(CMT)in the macular area, and changes in N1, P1 wave amplitude density and latency were observed after treatment in both groups.RESULTS:The BCVA(letter number)of the two groups were improved(P&#x003C;0.05), and the CMT were decreased(P&#x003C;0.05). The improvement of BCVA(letter number)in the combined treatment group was better than that in the control group at 3 mo(17.42±3.29 vs 14.61±3.14, P&#x003C;0.001)and 5 mo(19.75±3.25 vs 16.81±2.77, P&#x003C;0.001)after treatment; compared with the control group, CMT of the combined treatment group was thinner than that of the control group at 3 mo(304.58±53.34 vs 351.94±52.99 μm, P&#x003C;0.001)and 5 mo(274.17±62.26 vs 321.78±63.22 μm, P&#x003C;0.05)after treatment. The amplitude density of N1 and P1 wave in mfERG in both groups at 3 mo after treatment was higher than that before treatment(P&#x003C;0.05), and r1-r3 latency of P1 wave was shorter than that before treatment(P&#x003C;0.05), with no differences in the r1-r3 latency of N1 wave(P&#x003E;0.05). In addition, the amplitude density of N1 and P1 wave in the combined treatment group was higher than that in the control group at 3 mo after treatment(P&#x003C;0.05), the latency of P1 wave in the treatment group was significantly shorter than that in the control group(P&#x003C;0.05), and there was no significant difference in the latency of N1 wave between the two groups(P&#x003E;0.05).CONCLUSIONS:Mingmu-11 Pills combined with intravitreal injection of conbercept in the treatment of wARMD has obvious efficacy in improving vision and reducing macular edema.

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.

Research progress of related factors affecting poor response to wet age-related macular degeneration / 国际眼科杂志(Guoji Yanke Zazhi)

Wet age-related macular degeneration(wARMD)emerges as a primary contributor to irreversible vision impairment in the aging demographic. In clinical practice, anti-vascular endothelial growth factor(VEGF)therapies exhibit pronounced success in managing wARMD. However, in the actual clinical application, there are significant individual differences in the prognosis of anti-VEGF drug therapy, and some patients show poor response to the treatment, which may be related to the morphological differences of retinal layers in macular area, genetics, systemic conditions and other factors. It will help develop a more rational and individualized treatment plan to judge the prognosis of patients according to their different clinical manifestations in advance, so as to reduce overtreatment and the risk of retinal damage. In recent years, most studies on treatment response mainly focus on fundus morphology, genetics and so on. In this study, the relevant factors affecting adverse response to wARMD were reviewed, aiming to provide with more accurate treatment and prognostic monitoring programs for clinicians.

Research progress of microRNA in oxidative stress and lipid metabolism of non-exudative age-related macular degeneration / 国际眼科杂志(Guoji Yanke Zazhi)

Age-related macular degeneration(ARMD)is a neurodegenerative disease associated with oxidative stress. It is characterized by progressive death of photoreceptors and retinal pigment epithelium(RPE), and is one of the leading causes of irreversible loss of central vision in patients over the age of 65 years old. MicroRNA(miRNA)is a class of regulatory short-chain non-coding RNA that can bind and inhibit multiple gene targets in the same biological pathway. This unique property makes microRNA an ideal target for exploring the pathogenesis, diagnosis and treatment of non-exudative ARMD. Previous studies have found that the pathogenesis of non-exudative ARMD involves age, genetics, environment, oxidative stress, lipid metabolism, autophagy and immunity. However, the exact mechanisms have not been fully clarified. As biomarkers of non-exudative ARMD, miRNA play a role in oxidative stress and lipid metabolism. This article summarizes the role of various miRNA in targeting Nrf2 and HIF-1α to inhibit hypoxia-related angiogenesis signaling, thereby affecting oxidative stress. Additionally, miRNA regulate lipid uptake and the expression of ABCA1 in RPE and macrophages, thereby influencing lipid metabolism. This deepens the understanding of the role of miRNA in oxidative stress and lipid metabolism in non-exudative ARMD, and provides directions for further improving the understanding of the pathogenesis and prevention of non-exudative ARMD.

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.

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.

Charles Bonnet syndrome in age-related macular degeneration - prevalence and clinical features in a Portuguese population / Síndrome de Charles Bonnet na degeneração macular relacionada à idade - prevalência e características clínicas numa população portuguesa

ABSTRACT Objective: Age-related macular degeneration (AMD) is the most prevalent cause of irreversible visual loss in the developed world. In late stages, it may lead to extremely low visual acuities, especially when associated with geographic atrophy or choroidal neovascularization. According to recent literature, Charles Bonnet syndrome (CBS) may be a rather common feature of late AMD. Methods: One hundred patients with late-stage age-related macular degeneration were actively asked whether they had symptoms of Charles Bonnet syndrome. Those that answered positively underwent a comprehensive questionnaire about the details of the visual hallucinations. Results: The following factors were significantly associated with Charles Bonnet syndrome: older age (+6.3 years; p=0.003), lower visual acuity in the better eye (Charles Bonnet Syndrome Group: 0.11; Non-Charles Bonnet Syndrome Group: 0.42; p=0.005) and female sex (Charles Bonnet Syndrome Group: 88%; Non-Charles Bonnet Syndrome Group: 43%; p=0.02). The visual hallucinations occurred mainly straight ahead (n=5), once per day (n=4), at no particular time (n=6), lasted some minutes (n=5), and disappeared after blinking (n=3) or looking away (n=3). The majority of patients lived alone (n=7), had not told anyone about the hallucinations (n=6), and associated the episodes with severe distress (n=5). Conclusion: Charles Bonnet syndrome was fairly prevalent in this late-stage age-related macular degeneration population. Our sample shows the importance of directly asking subjects about Charles Bonnet syndrome since they are often reluctant to admit to having visual hallucinations. Reassurance about its benignity is crucial to improve their quality of life.

RESUMO Objetivo: A doença macular ligada à idade (DMI) é a causa mais prevalente de perda visual irreversível nos países desenvolvidos. Em estadios avançados, esta doença pode levar a acuidades visuais extremamente baixas. De acordo com literatura recente, a Síndrome de Charles Bonnet (SCB) pode acontecer de forma relativamente comum na DMI tardia. Métodos: Cem doentes com degeneração macular da idade avançada foram interrogados ativamente sobre terem sintomas da síndrome de Charles Bonnet. Os que responderam de forma positiva foram submetidos a um questionário oral detalhado sobre os pormenores das alucinações visuais. Resultados: Os seguintes fatores foram significativamente associados à síndrome de Charles Bonnet: idade avançada (+6,3 anos; p=0,003), menor melhor acuidade visual corrigida no melhor olho (Grupo com Síndrome de Charles Bonnet: 0,11; Grupo sem Síndrome de Charles Bonnet: 0,42; p=0,005) e sexo feminino (Grupo com Síndrome de Charles Bonnet: 88%; Grupo sem Síndrome de Charles Bonnet: 43%; p=0,02). As alucinações visuais ocorriam principalmente em frente (n=5), uma vez por dia (n=4), em qualquer altura do dia (n=6), duravam alguns minutos (n=5) e desapareciam após pestanejo (n=3) ou desvio do olhar (n=3). A maioria dos doentes vivia sozinha (n=7), não tinha partilhado sua condição com ninguém (n=6) e associava os episódios a uma sensação angustiante (n=5). Conclusão: A síndrome de Charles Bonnet teve prevalência relativamente alta nessa população de degeneração macular da idade. Nossa amostra sublinha a importância de questionar diretamente sobre síndrome de Charles Bonnet, uma vez que os doentes se sentem muitas vezes relutantes em admitir alucinações visuais. A reafirmação da benignidade da situação é crucial para aumentar a qualidade de vida desses indivíduos.

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.

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.

Causality between type 2 diabetes mellitus and age-related macular degeneration: a Mendelian randomization study / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To analyze the causality between type 2 diabetes mellitus(T2DM)and age-related macular degeneration(ARMD)based on two-sample Mendelian randomization(MR).METHODS: T2DM and ARMD samples were extracted from the FinnGen database. Inverse variance weighted(IVW)was used as the main analysis method, MR-Egger and weighted median(WM)as supplementary methods to analyze the potential relationship between them. In addition, Cochran Q test and MR-Egger intercept were also used to analyze the sensitivity, and the P-value was used as the index of research results.RESULTS: IVW showed that T2DM was associated with the incidence of exudative ARMD(OR=1.14, 95%CI 1.01～1.28, P=0.021), but it was not significantly associated with the incidence of atrophic ARMD(OR=0.96, 95%CI 0.86～1.07, P=0.554). The results of sensitivity analysis confirmed that there was no heterogeneity and pleiotropy in this study, and the results were reliable.CONCLUSION: There is a causal relationship between T2DM and exudative ARMD. Considering the high rate of blindness caused by ARMD, it is of great significance to recognize and control the risk factors of ARMD to reduce its prevalence rate and early diagnosis and treatment.