Research progress of tight junction between retinal pigment epithelium cells and its disruption in the pathogenesis of age-related macular degeneration / 国际眼科杂志(Guoji Yanke Zazhi)

Age-related macular degeneration(AMD)is a common eye disease causing irreversible visual impairment in the elderly. The tight junction(TJ)between retinal pigment epithelium cells(RPECs)is an important structural unit of the outer blood retinal barrier(oBRB). The TJ is defective in the pathogenesis of AMD, which in turn promotes the destruction of oBRB and accelerates the occurrence and progression of AMD. In this paper, the roles of TJ and TJ protein in maintaining oBRB function, TJ protein abnormality and oBRB destruction in the pathogenesis of AMD were reviewed, aiming to provide new ideas for the treatment of AMD.

Application of optical coherence tomography angiography to evaluation of clinical effect of antivascular endothelial growth factor agents on wet age-related macular degeneration / 上海交通大学学报（医学版）

Objective: To apply optical coherence tomography angiography (OCTA) to evaluate the clinical effects of intravitreal injection of antivascular endothelial growth factor (VEGF) agents on wet age-related macular degeneration (AMD). Methods: The 31 eyes of 31 wet AMD patients in the Department of Ophthalmology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine from April 2018 to December 2018 were included. These patients received monthly intravitreal injection of anti-VEGF agents for three consecutive months. The best-corrected visual acuity (BCVA) before and 1, 2 and 3 months after first injection was compared. The macular fovea thickness and choroidal neovascularization (CNV) area at different time points before and after treatment were detected by OCTA and compared. Results: The baseline BCVA (logarithm of the minimum angle of resolution) of the included patients was 0.93±0.43, and the BCVA was significantly improved after treatment (P<0.05). The results of OCTA showed that before treatment the inner limiting membrane-retinal pigment epithealium thickness and inner limiting membrane-retinal pigment epithelial fit thickness were (329.03±110.73) μm and (468.84±209.50) μm, respectively, and they both decreased significantly after treatment (P<0.05). The CNV area before treatment was (4.78±3.24) mm2, and it decreased gradually with time after treatment (P<0.05). Conclusion: Intravitreal injection of anti-VEGF agents can reduce macular edema and inhibit CNV in the wet AMD patients. OCTA can be used to evaluate the efficacy of intravitreal injection of anti-VEGF agents in the treatment of wet AMD.

Association between C-reactive protein and age-related macular degeneration

Background: Age-related macular degeneration (AMD) is the leading cause of irreversible visual impairment among the elderly, worldwide affecting 30-50 million individuals. Inflammation is now increasingly thought to be a key risk factor for AMD. The association of CRP with AMD has been reported in only a few studies, with somewhat inconsistent results. The present study was undertaken to determine the association between AMD and serum CRP levels.Methods: A total of 53 patients diagnosed of any form of AMD fulfilling inclusion and exclusion criteria were included. A 5 mL sample of venous blood (non-fasting) was collected to determine serum high-sensitivity CRP levels (hsCRP). Different stages of AMD and serum hs CRP level were compared using one-way ANOVA test and calculated p value <0.05 was considered as statistically significant. Comparison between the two groups, one with risk factor and one without risk factor was performed using student-t test and calculated p value <0.05 was considered statistically significant.Results: Out of 53 patients 21 were having early AMD, 21 were having intermediate AMD and 11 were having advanced AMD. The mean serum hs CRP level was 0.14±0.05 mg/dL, 0.20±0.09 mg/dL and 0.28±0.08 mg/dL in early, intermediate and advanced AMD respectively. When statistically analysed the difference of mean serum hs CRP level among the three groups was found to be statistically significant.Conclusions: Type of AMD influence the baseline hsCRP level. Smoking and diabetes are associated with higher baseline serum hsCRP in all stages of AMD.

An efficacy analysis of anti-vascular endothelial growth factor therapy for choroidal neovascularization secondary to multifocal choroiditis and comparison with wet age-related macular degeneration / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

OBJECTIVE@#To evaluate the effect of anti-vascular endothelial growth factor (VEGF) on juxtafoveal choroidal neovascularization (CNV) secondary to multifocal choroiditis (MFC) and wet age-related macular degeneration (AMD).@*METHODS@#In this retrospective, comparative study, 20 unique eyes with CNV were divided into two groups: 10 patients affected by MFC and 10 patients diagnosed with wet AMD. They all received local intravitreal (IVT) injections of ranibizumab, with 6 months of follow-up. Retreatment injections were performed based on findings suggestive of active neovascularization.@*RESULTS@#Significant improvements were observed in the juxtafoveal CNV lesions, and average central macular thickness decreased in both groups following the anti-VEGF therapy (P<0.05). The average number of injections used in MFC patients was 1.6, while three injections on average were used in wet AMD patients (Z=-2.844, P=0.009). Best-corrected visual acuity was significantly improved in MFC patients after anti-VEGF therapy (P<0.05), and there was no significant difference in wet AMD patients between before anti-VEGF therapy and 6 months later (P>0.05).@*CONCLUSIONS@#IVT ranibizumab resulted in good clinical outcomes for juxtafoveal CNV secondary to MFC and wet AMD, but the average number of injections used in MFC was fewer than that used in wet AMD over a 6-month observation period. Compared with the wet AMD group, visual acuity was obviously improved in the MFC group at 6 months.

Long-term Results of Taking Anti-oxidant Nutritional Supplement in Intermediate Age-related Macular Degeneration

PURPOSE: We prospectively investigated clinical changes and long-term outcomes after administration of the drugs recommended by the Age-Related Eye Disease Study-2 to patients with intermediate age-related macular degeneration (AMD). METHODS: This prospective multicenter study enrolled 79 eyes of 55 patients taking lutein and zeaxanthin. The primary endpoint was contrast sensitivity; this was checked every 12 months for a total of 36 months after treatment commenced. The secondary endpoints were visual acuity, central macular thickness, and drusen volume; the latter two parameters were assessed using spectral domain optical coherence tomography. RESULTS: The mean patient age was 72.46 ± 7.16 years. Contrast sensitivity gradually improved at both three and six cycles per degree. The corrected visual acuity was 0.13 ± 0.14 logMAR and did not change significantly over the 36 months. Neither the central macular thickness nor drusen volume changed significantly. CONCLUSIONS: Contrast sensitivity markedly improved after treatment, improving vision and patient satisfaction. Visual acuity, central retinal thickness, and drusen volume did not deteriorate. Therefore, progression of AMD and visual function deterioration were halted.

Summarize drug dosage forms in treatment of age-related macular degeneration disease / 中国中药杂志

In this review, the authors summarized the drugs in treatment of the age-related macular degeneration (AMD or ARMD), including the pathogenesis of the age-related macular degeneration at home and abroad, dosage forms used in the treatment, and the drugs research and development directions in the future. AMD disease is the third largest blinding diseases all over the world, with an incidence of 6.62%. The dosage form of the traditional medicine is mostly oral formulations, playing a role in body, while the newly dosage form is topical drug delivery formulation. Traditional Chinese medicine (TCM) has certain advantages in the treatment of AMD disease and the development of topical drug delivery preparations with newly preparation technologies would have a very bright prospect in the future.

Some aspect of diagnosis and type of clinical management and risk factors of age-related macular degeneration / Шинэ санаа Шинэ нээлт

Age-related macular degeneration (AMD) is the leading cause of severe visual loss in people aged 50 years or older. It estimates that 25-35 million people lost vision due to AMD in the world. Rapid increase of aging population, 33.2 million people was affected by AMD in 1994and there is estimation the number will reach 80 million by 2050. Prevalence of disease is different in countries it relates due to aging population and the ratio is higher in developed countries. The risk factors of AMD; race, nationality, life style, cigarette smoking, alcoholconsumption, UV exposure, diet, vitamin or food supplements consumption, drugs and high blood pressure. This study was to evaluate risk factors in age related macular degeneration because cigarette smoking, alcohol consumption and high blood pressure are high among elder Mongolians. Introduction of Optical Coherent Tomography /OCT/ in ophthalmology enables us to early diagnose and prevention. It will be basic data for developing AMD prevention policy and improving methods of diagnosis and management.

Perspectivas farmacológicas futuras en el tratamiento de la degeneración macular relacionada a la edad (DMRE) neovascular. Parte 1: fármacos en estudios clínicos / Pharmacological future perspectives in the treatment of age-related macular degeneration (AMD) neovascular. Part 1: drugs in clinical trials

Objetivos: Presentar una revisión de los nuevos y posibles objetivos de tratamiento farmacológicos para la degeneración macular relacionada a la edad neovascul r y el estado de los fármacos en estudios clínicos. Diseño del estudio: Revisión de tema. Métodos: Se realizó una búsqueda de la literatura electrónica disponible en EMBASE, PUBMED y Google Scholar acerca del tema, y se complementa con la información encontrada en www.clinicaltrials.gov y la plataforma de registros internacionales de ensayos clínicos de la O.M.S. Se procedió a sistematizar la información y se presenta en forma estructurada. Conclusiones: Las nuevas opciones terapéuticas para la degeneración macular relacionada la edad neovascular proporcionan múltiples objetivos farmacológicos, los cuales se alcanzan realizando modificaciones a moléculas ya elaboradas o con nuevos fármacos los cuales pueden actuar tanto como terapia adjunta a los actuales medicamentos antiangiogénicos (anti VEGF) mejorando su eficacia o con nuevas opciones sustitutivas. Meritorio destacar la vía de la tirosina-quinasa, la cual había sido abordada con los existentes anti VEGF, ahora se presentan nuevas opciones terapéuticas que actúan corriente abajo. Diversos fármacos se encuentran en estudios de efi cacia parcial, merecen especial mención Fovista® y conbercept de los cuales ya se encuentran en desarrollo estudios fase III.

Objectives: To present a review of new and potential targets for pharmacological treatment for neovascular age-related macular degeneration and the state of drugs in development of clinical studies. Study design: Literature review. Methods: A search of electronic literature available in EMBASE, PubMed and Google Scholar on the subject is made and compliments the information found on www.clinicaltrials. gov and platform of international clinical trials registers of the W.H.O. Conclusions: N ew therapeutic options for neovascular age-related macular degeneration provide multiple targets, which are achieved by performing modifi cations to a molecule already developed or new drugs which can act both as an adjunct to current anti VEGF improving efficiency or new alternative options. Meritorious note the tyrosine kinase way, on which previously it has acted with existing anti VEGF, now presents new therapeutic options that act downstream. Several drugs are in partial effi cacy studies, deserve special mention Fovista and conbercept of which already studies are in development phase III.

Perspectivas farmacológicas de futuro en el tratamiento de la degeneración macular relacionada a la edad (DMRE) neovascular. Parte 2: terapia génica y fármacos en estudios pre clínicos / Pharmacological future perspectives in the treatment of age-related macular degeneration (AMD) neovascular. Part 2: gene therapy and drugs in pre-clinical trials

Objetivos: presentar una revisión acerca de la terapia génica y los fármacos en estudios preclínicos como nuevos y posibles blancos de tratamiento farmacológicos para la degeneración macular relacionada a la edad neovascular y el estado de los estudios clínicos de los mismos. Diseño del estudio: revisión de tema. Métodos: se realizó una búsqueda de la literatura electrónica disponible en EMBASE, PUBMED y Google Scholar acerca del tema y se complementa con la información encontrada en www.clinicaltrials.gov y la plataforma de registros internacionales de ensayos clínicos de la OMS. Conclusiones: la terapia génica vinculada a la degeneración macular asociada a la edad neovascular muestra un avance científico importante en el campo de la farmacología ocular pudiendo proporcionar eficacia tras una sola inyección de un vector que puede expresar continuamente una proteína elegida. Existen estudios pre-clínicos que sugieren nuevos y diversos blancos farmacológicos para la degeneración macular relacionada a la edad mostrando un perfil de seguridad y eficacia significativo.

Objectives: to review gene therapy and drugs in preclinical studies as potential new targets for pharmacological treatment for agerelated macular degeneration neovascular and the state of development clinical trials. Study design: literature review. Methods: a search of electronic literature available in EMBASE, PubMed and Google Scholar on the subject was performed and complemented with information found on www.clinicaltrials.gov and WHO platform of international clinical trials registers. Conclusions: the gene therapy linked to age-related macular degeneration shows a scientific important advance in the field of the ocular pharmacology being able to provide efficiency after a single injection of a vector that can express a chosen protein. There are preclinical studies that suggest new and different pharmacological targets for age-related macular degeneration showing a significant safety and efficacy profile.

Decreased VEGF-A and sustained PEDF expression in a human retinal pigment epithelium cell line cultured under hypothermia

BACKGROUND: Previous reports have described a decrease in retinal temperature and clinical improvement of wet age-related macular degeneration (AMD) after vitrectomy. We hypothesized that the retinal temperature decrease after vitrectomy plays a part in the suppression of wet AMD development. To test this hypothesis, we evaluated the temperature dependence of the expression of vascular endothelial growth factor-A (VEGF-A) and in vitro angiogen-esis in retinal pigment epithelium (RPE). RESULTS: We cultured ARPE-19 cells at 37, 35, 33 and 31°C and measured the expression of VEGF-A, VEGF-A splicing variants, and pigment epithelium-derived factor (PEDF). We performed an in vitro tube formation assay. The dehydrogenase activity was also evaluated at each temperature. Expression of VEGF-A significantly decreased with decreased temperature while PEDF expression did not. VEGF165 expression and in vitro angiogenesis also were temperature dependent. The dehydrogenase activity significantly decreased as the culture temperature decreased. CONCLUSIONS: RPE cultured under hypothermia that decreased cellular metabolism also had decreased VEGF-A and sustained PEDF expression, creating an anti-angiogenic environment. This mechanism may be associated with a beneficial effect after vitrectomy in patients with wet AMD.

A Case of Age Related Macular Degeneration Responding to a Statin – Perspective for a New Treatment.

The newly started use of atorvastatin eliminated the need for further intravitreal injections of ranibizumab for 37 months in a case of wet form of age related macular degeneration(AMD). Repeated optical coherence tomographic examinations documented the absence of intra- or subretinal fluid. The known effects of statins on endothelial function might also improve retinal capillary endothelial function and reduce or eliminate fluid leakage into the intra- or subretinal space. This would intervene earlier in one important disease mechanism of AMD than the injection of anti-VEGF therapies. A randomized study is necessary to prove this hypothesis.

Photodynamic Therapy of Choroidal Neovascularization in Age-Related Macular Degeneration with Verteporfin: An Analysis of 10 Years of Clinical Results

PURPOSE: To analyze the long-term results of photodynamic therapy (PDT) for exudative age-related macular degeneration (AMD). METHODS: The clinical data of patients treated with photodynamic therapy for exudative age-related macular degeneration between April 2000 and December 2000 were analyzed. Patients were followed-up for at least 10 years after PDT. RESULTS: Twenty-nine eyes of 29 patients were enrolled. Mean visual acuity on the logarithm of the minimum angle of resolution (log MAR) scale was 0.78 +/- 0.34 at baseline, 1.01 +/- 0.42 at 60 months, and 1.02 +/- 0.41 at 120 months. Predominantly classic, minimally classic, and occult without classic choroidal neovascularization was noted in 51.7%, 17.2%, and 31.1% of patients, respectively. Visual acuity was improved by 1 or more lines in 27.6% of patients and was unchanged in 20.7% of patients, while 51.7% of patients had lost 1 or more lines of visual acuity by 120 months. Baseline visual acuity and age were associated with the final visual prognosis (p < 0.05). Four patients developed neovascular AMD in the contralateral eye. CONCLUSIONS: PDT is safe and effective for neovascular AMD. However, AMD can recur at any time and thus patients should be followed-up for a long period of time.

Anatomical Non-Responder to Intravitreal Bevacizumab for Neovascular Age-Related Macular Degeneration

PURPOSE: To analyze the characteristics of anatomical non-response to intravitreal bevacizumab (IVB) in patients with neovascular age-related macular degeneration (AMD). METHODS: Neovascular AMD patients who were treated with IVB were studied. A non-responder was defined as a patient whose eyes had no change in choroidal neovascularization (CNV) lesion size or fluorescein leakage and no change in foveal thickness (FT) after at least two administrations of IVB. Demographic findings and efficacy outcomes were compared between responders and non-responders based on patient gender, age, visual acuity (VA), FT, CNV lesion type, CNV lesion size, presence of serous retinal detachment (SRD), presence of pigment epithelial detachment (PED), PED size, and presence of sub-macular hemorrhage (SMH). RESULTS: Five patients (six eyes; 13.6%) were identified as non-responders to treatment with IVB. The mean age of the non-responder group (75.17 +/- 3.66 yers) was greater (p = 0.237) than that of the responder group (71.89 +/- 8.06 years), and the proportion of occult CNV (85.7% versus 55.3%, p = 0.375) was higher in the non-responder group, although there was no significant difference compared with that of the responder group. The PED size of the non-responder group (4.42 +/- 1.56 mm2) was significantly larger than that of the responder group (1.51 +/- 2.33 mm2, p = 0.001). CONCLUSIONS: The authors report a group of patients in AMD with poor treatment response to IVB. The PED size of the non-responder group was confirmed to be significantly larger than that of the responder group.

Atualização no diagnóstico e tratamento da degeneração macular relacionada à idade / Highlights on age-related macular degeneration diagnosis and treatment

A degeneração macular relacionada à idade (DMRI) representa a principal causa de cegueira legal em pacientes idosos no mundo ocidental. O presente artigo revisa os principais avanços no diagnóstico e tratamento da DMRI, servindo de auxílio para a atualização da comunidade médica quanto a esta doença (AU)

Age-related macular degeneration (AMD) is the leading cause of legal blindness in the elderly in the Western world. In this regard, to promote the medical education about this disease, we present a review of AMD diagnostic and therapeutic approaches (AU)

Antioxidant effect of hydralazine on retinal pigment epithelial cells and its potential use in the therapy of age-related macular degeneration / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To investigate the antioxidant effect of hydralazine under hypoxia-induced damage on retinal pigment epithelial (ARPE-19) cells and the role of reactive oxygen species (ROS) in this effect.METHODS: Human retinal pigment epithelial (hRPE) cells were used to investigate the effect of hydralazine on oxidative stress, including tert-butyl hydroxyperoxide (t-BHP), H2O2, sodium azide (NaN3), and hypoxia induced cell damage. Cell viability was determined by MTT assay.RESULTS: When ARPE-19 cells were treated with oxidative stress induced by ROS, hydralazine showed concentration-dependent protection against t-BHP, H2O2 and hypoxia induced cell damage but not NaN3. Nitric oxide (NO) was not involved in this effect.CONCLUSION: Hydralazine showed antioxidant potential against oxidative stress induced damage in ARPE-19 cells. These effects might be caused through scavenger of ROS. Thus, hydralazine could be used for the treatment of age-related macular degeneration (AMD).

Retinal pigment epithelial and choroidal atrophy in wet age-related macular degeneration treated with multiple transpupillary themotherapy:A case report / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To report a case of wet age-related macular degeneration (AMD) treat with multiple transpupillary themotherapy (TTT) and choroidal neovascularization (CNV) disappeared but retinal pigment epithelial(PRE) and choroidal atrophy occurred with a low vision at the end point.METHODS: Clinical data including fundus hotographs, fundus fluorescein angiography (FFA), indocyanine angiography (ICGA) and optical coherence tomography(OCT) was reviewed.RESULTS: A 72-year-old man complained about blurred vision of his left eye and FFA revealed polypoidal choroidal vasculopathy (PCV) in the macula. His left eye had stable vision of 0.1 for 6 years without any treatment of CNV. About 2 years later, his right eye presented a piece of CNV. During the period of 3 years, the lesion remained more (3×5 PD) and less (1×2PD) in size with remarkable exudates and bleeding, and 7 sessions of TTT were applied with 80-280mW, 2mm of spot, and 60 seconds exposure and with the interval of 3 months or more. The CNV lesion finally disappeared, but there left a white area in the macula and vision decreased from 0.3 to 0.04.CONCLUSION: Although CNV lesion can be eliminated by TTT, obvious atrophy of RPE cells and the choroids can happen and this may not be of help for patient vision. It suggests that the parameters of TTT will be lower than 120 mW/mm and limited less two sessions if applicable, especially for Asia people.

Photodynamic Therapy for Choroidal Neovascularization Secondary to Age-Related Macular Degeneration

PURPOSE: To investigate the effects of repeated photodynamic therapy (PDT) for subfoveal choroidal neovascularization secondary to age-related macular degeneration (AMD) in Korean patients. METHODS: Clinical data of patients who were treated with repeated (3 times or more) PDT for subfoveal choroidal neovascularization secondary to AMD and followed up for more than 6 months were collected from 17 hospitals around the country. Visual outcomes at 12 and 24 months, follow-up were compared between subtypes of choroidal neovascularization. The factors related to final visual prognosis and PDT-related adverse effects were evaluated. RESULTS: 244 patients (244 eyes) were recruited (male: 60%, age: 67.7+/-9.1 years). The portion of patients with predominantly classic, minimally classic, and occult without classic choroidal neovascularization was 57%, 13%, and 24%, respectively and that of patients with visual improvements or less than moderate visual loss at 24 months follow-up were 28%, 38%, 30% and 47%, 56%, and 65%, respectively. Baseline visual acuity and age were significantly related to the final visual prognosis (p<0.05). PDT-related adverse events developed in 15 (6.1%) patients, but most were mild and transient. CONCLUSIONS: Repeated PDT for subfoveal choroidal neovascularization secondary to AMD has effects comparable to those of previous prospective, controlled trials without any significant safety concerns in Korea.

Correlation of OCT and Preferential Hyperacuity Perimeter in Exudative Age-related Macular Degeneration

PURPOSE: Preferential hyperacuity perimeter (PHP) is a device that measures metamorphopsia in the central 14 degrees of the macular visual field which is presented by hyperacuity defect. We elucidated a hyperacuity defect lesion of PHP in exudative age-related macular degeneration (AMD) by Optical coherence tomography (OCT). METHODS: Nineteen eyes of 18 patients with exudative AMD diagnosed by fundus examination and fluorescein angiography (FA) underwent PHP. We then elucidated any hyperacuity defect lesion of PHP by fundus photography, FA and OCT. For a control, 20 eyes of 10 age-matched persons who had no ophthalmological abnormality underwent PHP and OCT to determine if hyperacuity defect would appear. RESULTS: Hyperacuity defect lesion appeared in 18 eyes (95%) of AMD patients. There was good locational correlation between the hyperacuity defect lesions and lesions in the fudoscopic examination in 16 eyes of 18, but there was a counterpart relation at the superior-inferior and left-right in 2 eyes. Hyperacuity defect lesion in PHP was of smooth or irregular elevation of the retinal pigment epithelium (RPE) in OCT. In the control, hyperacuity defect lesion appeared in 1 eye (5%) and it was normal in OCT. CONCLUSIONS: PHP showed a highly positive rate in detecting AMD-related lesion. The hyperacuity defects that are noted by the PHP are produced from elevation of the RPE.