Vitrectomy for Subretinal and Submacular Hemorrhages

Retinal Diseases ◽

Anti Vegf ◽

Age Related ◽

Underlying Pathology

Submacular hemorrhage (SMH) is relatively rare in retinal practice. However, it is an important complication of many choroidal and retinal diseases, particularly neovascular age-related macular degeneration (AMD). When untreated the visual prognosis is poor, especially in patients with AMD, and SMHs cannot be effectively treated with only anti-vascular endothelial growth factor (anti-VEGF) injection. The current therapeutic approach is based upon the displacement of the subretinal hemorrhage away from the central retina as soon as possible. The use of tissue plasminogen activator (tPA) has been an important milestone in the treatment of SMHs. Current vitrectomy techniques for SMH management include subretinal tPA injection and aspiration of the blood, and subretinal tPA, and air/anti-VEGF injection with gas tamponade. Submacular surgery, which involves removal of the SMH and choroidal neovascularization (CNV) through a retinotomy, seems to be a technique reserved for selected cases where central retinal pigment epithelium appears to be undiseased/uninvolved. Among the non-surgical treatment options, pneumatic displacement with intravitreal tPA and gas injection may be preferred especially for small-medium sized and thin SMHs. However, the favored approach in real-life conditions is shaped by the physician's experience and the available treatment options. Regardless of the preferred approach, the continuity of the treatment of the underlying pathology is important. As the underlying pathology is usually a CNV, the continuation of anti-VEGF treatment is important for maintaining the visual gain of the initial treatment and reducing the risk of recurrent SMH. The breakthrough development rate of the drugs and the surgical techniques for the treatment of retinal diseases promises in terms of new and more effective treatment approaches.

LRG1 Expression Is Elevated in the Eyes of Patients with Neovascular Age-Related Macular Degeneration

International Journal of Molecular Sciences ◽

10.3390/ijms22168879 ◽

2021 ◽

Vol 22 (16) ◽

pp. 8879

Author(s):

Lucia Mundo ◽

Gian Marco Tosi ◽

Stefano Lazzi ◽

Grazia Pertile ◽

Barbara Parolini ◽

...

Keyword(s):

Macular Degeneration ◽

Aqueous Humor ◽

Smooth Muscle Actin ◽

Pigment Epithelium ◽

Retinal Pigment ◽

Average Concentration ◽

Surrounding Tissue ◽

Anti Vegf ◽

Leucine-rich a-2-glycoprotein 1 (LRG1) is a candidate therapeutic target for treating the neovascular form of age-related macular degeneration (nvAMD). In this study we examined the expression of LRG1 in eyes of nvAMD patients. Choroidal neovascular membranes (CNVMs) from patients who underwent submacular surgery for retinal pigment epithelium–choroid graft transplantation were collected from 5 nvAMD patients without any prior intravitreal anti-VEGF injection, and from six patients who received intravitreal anti-VEGF injections before surgery. As controls free of nvAMD, retina sections were obtained from the eyes resected from a patient with lacrimal sac tumor and from a patient with neuroblastoma. CNVMs were immunostained for CD34, LRG1, and α-smooth muscle actin (α-SMA). Aqueous humor samples were collected from 58 untreated-naïve nvAMD patients prior to the intravitreal injection of anti-VEGF and 51 age-matched cataract control patients, and LRG1 concentration was measured by ELISA. The level of LRG1 immunostaining is frequently high in both the endothelial cells of the blood vessels, and myofibroblasts in the surrounding tissue of CNVMs of treatment-naïve nvAMD patients. Furthermore, the average concentration of LRG1 was significantly higher in the aqueous humor of nvAMD patients than in controls. These observations provide a strong experimental basis and scientific rationale for the progression of a therapeutic anti-LRG1 monoclonal antibody into clinical trials with patients with nvAMD.

C-reactive protein isoforms differentially affect outer blood-retinal barrier integrity and function

AJP Cell Physiology ◽

10.1152/ajpcell.00057.2016 ◽

2017 ◽

Vol 312 (3) ◽

pp. C244-C253 ◽

Cited By ~ 7

Author(s):

Blanca Molins ◽

Anna Pascual ◽

Méndez ◽

Victor Llorenç ◽

Javier Zarranz-Ventura ◽

...

Keyword(s):

Pigment Epithelium ◽

Retinal Pigment ◽

Protein Isoforms ◽

C Reactive Protein ◽

Barrier Dysfunction ◽

Blood Retinal Barrier ◽

Reactive Protein ◽

Anti Vegf ◽

The retinal pigment epithelium (RPE) forms the outer blood-retinal barrier (oBRB) and is the prime target of early age-related macular degeneration (AMD). C-reactive protein (CRP), a serum biomarker for chronic inflammation and AMD, presents two different isoforms, monomeric (mCRP) and pentameric (pCRP), that may have a different effect on inflammation and barrier function in the RPE. The results reported in this study suggest that mCRP but not pCRP impairs RPE functionality by increasing paracellular permeability and disrupting the tight junction proteins ZO-1 and occludin in RPE cells. Additionally, we evaluated the effect of drugs commonly used in clinical settings on mCRP-induced barrier dysfunction. We found that a corticosteroid (methylprednisolone) and an anti-VEGF agent (bevacizumab) prevented mCRP-induced ARPE-19 barrier disruption and IL-8 production. Furthermore, bevacizumab was also able to revert mCRP-induced IL-8 increase after mCRP stimulation. In conclusion, the presence of mCRP within retinal tissue may lead to disruption of the oBRB, an effect that may be modified in the presence of corticosteroids or anti-VEGF drugs.

Gene editing prospects for treating inherited retinal diseases

Journal of Medical Genetics ◽

10.1136/jmedgenet-2019-106473 ◽

2019 ◽

Vol 57 (7) ◽

pp. 437-444 ◽

Cited By ~ 6

Author(s):

Daniela Benati ◽

Clarissa Patrizi ◽

Alessandra Recchia

Keyword(s):

Genome Editing ◽

Genetic Disorder ◽

Retinal Pigment ◽

Treatment Options ◽

Genetic Defect ◽

Retinal Dystrophy ◽

Retinal Pigment Epithelial Cells ◽

Retinal Diseases ◽

Retinal diseases (RD) include inherited retinal dystrophy (IRD), for example, retinitis pigmentosa and Leber’s congenital amaurosis, or multifactorial forms, for example, age-related macular degeneration (AMD). IRDs are clinically and genetically heterogeneous in nature. To date, more than 200 genes are known to cause IRDs, which perturb the development, function and survival of rod and cone photoreceptors or retinal pigment epithelial cells. Conversely, AMD, the most common cause of blindness in the developed world, is an acquired disease of the macula characterised by progressive visual impairment. To date, available therapeutic approaches for RD include nutritional supplements, neurotrophic factors, antiangiogenic drugs for wet AMD and gene augmentation/interference strategy for IRDs. However, these therapies do not aim at correcting the genetic defect and result in inefficient and expensive treatments. The genome editing technology based on clustered regularly interspaced short palindromic repeat (CRISPR)-associated protein (Cas) and an RNA that guides the Cas protein to a predetermined region of the genome, represents an attractive strategy to tackle IRDs without available cure. Indeed, CRISPR/Cas system can permanently and precisely replace or remove genetic mutations causative of a disease, representing a molecular tool to cure a genetic disorder. In this review, we will introduce the mechanism of CRISPR/Cas system, presenting an updated panel of Cas variants and delivery systems, then we will focus on applications of CRISPR/Cas genome editing in the retina, and, as emerging treatment options, in patient-derived induced pluripotent stem cells followed by transplantation of retinal progenitor cells into the eye.

The Cytoskeleton of the Retinal Pigment Epithelium: from Normal Aging to Age-Related Macular Degeneration

International Journal of Molecular Sciences ◽

10.3390/ijms20143578 ◽

2019 ◽

Vol 20 (14) ◽

pp. 3578 ◽

Cited By ~ 11

Author(s):

Ioana-Sandra Tarau ◽

Andreas Berlin ◽

Christine A. Curcio ◽

Thomas Ach

Keyword(s):

Retinal Pigment Epithelium ◽

Macular Degeneration ◽

Current Knowledge ◽

Pigment Epithelium ◽

Retinal Pigment ◽

Complex Structure ◽

Retinal Diseases ◽

Strong Connection ◽

The retinal pigment epithelium (RPE) is a unique epithelium, with major roles which are essential in the visual cycle and homeostasis of the outer retina. The RPE is a monolayer of polygonal and pigmented cells strategically placed between the neuroretina and Bruch membrane, adjacent to the fenestrated capillaries of the choriocapillaris. It shows strong apical (towards photoreceptors) to basal/basolateral (towards Bruch membrane) polarization. Multiple functions are bound to a complex structure of highly organized and polarized intracellular components: the cytoskeleton. A strong connection between the intracellular cytoskeleton and extracellular matrix is indispensable to maintaining the function of the RPE and thus, the photoreceptors. Impairments of these intracellular structures and the regular architecture they maintain often result in a disrupted cytoskeleton, which can be found in many retinal diseases, including age-related macular degeneration (AMD). This review article will give an overview of current knowledge on the molecules and proteins involved in cytoskeleton formation in cells, including RPE and how the cytoskeleton is affected under stress conditions—especially in AMD.

Retinal Diseases Associated with Oxidative Stress and the Effects of a Free Radical Scavenger (Edaravone)

Oxidative Medicine and Cellular Longevity ◽

10.1155/2017/9208489 ◽

2017 ◽

Vol 2017 ◽

pp. 1-14 ◽

Cited By ~ 58

Author(s):

Tomomi Masuda ◽

Masamitsu Shimazawa ◽

Hideaki Hara

Keyword(s):

Oxidative Stress ◽

Free Radical ◽

Apoptotic Cell ◽

Pigment Epithelium ◽

Retinal Pigment ◽

Free Radical Scavenger ◽

Radical Scavenger ◽

Retinal Diseases ◽

Oxidative stress plays a pivotal role in developing and accelerating retinal diseases including age-related macular degeneration (AMD), glaucoma, diabetic retinopathy (DR), and retinal vein occlusion (RVO). An excess amount of reactive oxygen species (ROS) can lead to functional and morphological impairments in retinal pigment epithelium (RPE), endothelial cells, and retinal ganglion cells (RGCs). Here we demonstrate that edaravone, a free radical scavenger, decreased apoptotic cell death, oxidative damage to DNA and lipids, and angiogenesis through inhibiting JNK and p38 MAPK pathways in AMD, glaucoma, DR, and RVO animal models. These data suggest that the therapeutic strategy for targeting oxidative stress may be important for the treatment of these ocular diseases, and edaravone may be useful for treating retinal diseases associated with oxidative stress.

Retinal Pigment Epithelium Tears: Risk Factors, Mechanism and Therapeutic Monitoring

Ophthalmologica ◽

10.1159/000439445 ◽

2015 ◽

Vol 235 (1) ◽

pp. 1-9 ◽

Cited By ~ 18

Author(s):

Christoph R. Clemens ◽

Nicole Eter

Keyword(s):

Retinal Pigment Epithelium ◽

Current Knowledge ◽

Pigment Epithelium ◽

Retinal Pigment ◽

Therapeutic Monitoring ◽

Temporal Association ◽

Anti Vegf ◽

Age Related ◽

Rpe Tear

Tears of the retinal pigment epithelium (RPE) are most commonly associated with vascularised RPE detachment due to age-related macular degeneration (AMD), and they usually involve a deleterious loss in visual acuity. Recent studies suggest an increase in RPE tear incidences since the introduction of anti-vascular endothelial growth factor (anti-VEGF) therapies as well as a temporal association between the tear event and the intravitreal injection. As the number of AMD patients and the number of administered anti-VEGF injections increase, both the challenge of RPE tear prevention and the treatment after RPE tear formation have become more important. At the same time, the evolution of retinal imaging has significantly contributed to a better understanding of RPE tear development in recent years. This review summarises the current knowledge on RPE tear development, predictive factors, and treatment strategies before and after RPE tear formation.

Retinal Pigment Epithelium Tears After Anti-Vascular Endothelial Growth Factor Therapy for Neovascular Age-Related Macular Degeneration

Ophthalmologica ◽

10.1159/000514991 ◽

2021 ◽

Author(s):

Jayoung Ahn ◽

Daniel Duck-Jin Hwang ◽

Joon Hong Sohn ◽

Gisung Son

Keyword(s):

Vascular Endothelial Growth Factor ◽

Visual Acuity ◽

Pigment Epithelium ◽

Retinal Pigment ◽

Vascular Endothelial ◽

Anti Vegf ◽

Age Related ◽

Endothelial Growth Factor ◽

Rpe Tear

Purpose: To assess the visual prognostic factors of retinal pigment epithelium (RPE) tears and describe their clinical features. Methods: The medical records of treatment-naive neovascular age-related macular degeneration patients who received intravitreal anti-vascular endothelial growth factor (VEGF) injections were retrospectively reviewed. Results: The incidence of RPE tears was 1.36% (10 out of 733 eyes). The type of anti-VEGF agent administered did not affect the incidence (p = 0.985). The median best-corrected visual acuity (BCVA) of 10 patients decreased after an RPE tear (0.4 to 0.6 logMAR); however, subsequent injections restored the BCVA to a level similar to that before the RPE tear (0.4 logMAR, p = 0.436). Central macular thickness improved significantly during the study (794.4 to 491.9 μm, p = 0.013). The final BCVA was positively correlated with the BCVA before and immediately after the RPE tear (p = 0.025 and 0.002, respectively) and was weakly correlated with foveal involvement of the RPE tear (p = 0.061). Conclusion: The incidence of RPE tears did not differ according to the type of anti-VEGF agent. The final BCVA was proportional to the BCVA before and after RPE tears. Continuous treatment with anti-VEGF after the occurrence of RPE tears can benefit the final visual acuity and macular anatomy.

Significance of Hyperreflective Foci as an Optical Coherence Tomography Biomarker in Retinal Diseases: Characterization and Clinical Implications

Journal of Ophthalmology ◽

10.1155/2021/6096017 ◽

2021 ◽

Vol 2021 ◽

pp. 1-10

Author(s):

Serena Fragiotta ◽

Solmaz Abdolrahimzadeh ◽

Rosa Dolz-Marco ◽

Yoichi Sakurada ◽

Orly Gal-Or ◽

...

Keyword(s):

Optical Coherence Tomography ◽

Macular Edema ◽

Diabetic Macular Edema ◽

Pigment Epithelium ◽

Retinal Pigment ◽

Retinal Diseases ◽

Optical Coherence ◽

Hyperreflective Foci ◽

Hyperreflective foci (HRF) is a term coined to depict hyperreflective dots or roundish lesions within retinal layers visualized through optical coherence tomography (OCT). Histopathological correlates of HRF are not univocal, spacing from migrating retinal pigment epithelium cells, lipid-laden macrophages, microglial cells, and extravasated proteinaceous or lipid material. Despite this, HRF can be considered OCT biomarkers for disease progression, treatment response, and prognosis in several retinal diseases, including diabetic macular edema, age-related macular degeneration (AMD), retinal vascular occlusions, and inherited retinal dystrophies. The structural features and topographic location of HRF guide the interpretation of their significance in different pathological conditions. The presence of HRF less than 30 μm with reflectivity comparable to the retinal nerve fiber layer in the absence of posterior shadowing in diabetic macular edema indicates an inflammatory phenotype with a better response to steroidal treatment. In AMD, HRF overlying drusen are associated with the development of macular neovascularization, while parafoveal drusen and HRF predispose to macular atrophy. Thus, HRF can be considered a key biomarker in several common retinal diseases. Their recognition and critical interpretation via multimodal imaging are vital to support clinical strategies and management.

Incidence of Retinal Pigment Epithelial Tears and Associated Risk Factors After Treatment of Age-Related Macular Degeneration with Intravitreal Anti-VEGF Injections§

The Open Ophthalmology Journal ◽

10.2174/1874364101408010101 ◽

2014 ◽

Vol 8 (1) ◽

pp. 101-104 ◽

Cited By ~ 6

Author(s):

Theodoros Empeslidis ◽

Athanasios Vardarinos ◽

Vasileios Konidaris ◽

Soon Wai Ch'ng ◽

Bharat Kapoor ◽

...

Keyword(s):

Risk Factors ◽

Retinal Pigment Epithelium ◽

Macular Degeneration ◽

Pigment Epithelium ◽

Retinal Pigment ◽

Anti Vegf ◽

Age Related ◽

Associated Risk Factors ◽

Rpe Tear

Purpose : To study the incidence and risk factors for retinal pigment epithelium tears following intravitreal anti-vascular endothelial growth factor (VEGF) injections. Methods : Retrospective longitudinal study. 4027 intravitreal anti-VEGF injections in 628 patients (676 eyes) for choroidal neovascularisation associated with age related macular degeneration in a period of 18 months were studied. Results : Seventeen patients (mean age 83.95±5.84) developed retinal pigment epithelium tears. The incidence rate was 0.4%. Fibrovascular pigment epithelium detachment (PED) was previously observed in all cases. In 88 % (15/17) of AMD patients that had a RPE tear, PED height was found to be less than 400 microns at presentation. In 5 of 7 patients with RPE tear grade <4, continuing of anti-VEGF treatment resulted to improvement of visual acuity. Conclusion : Critical risk factors for RPE tears are presence of PED as well as advanced age. Visual improvement appears to depend more on the extent and location of the RPE tear and less on the PED height.

Nutraceutical «Resvega Forte» in complex treatment of neovascular age-related macular degeneration against the background of anti-VEGF therapy

Modern technologies in ophtalmology ◽

10.25276/2312-4911-2021-3-312-316 ◽

2021 ◽

pp. 312-316

Author(s):

L.P. Danilova ◽

◽

V.V. Egorov ◽

G.P. Smoliakova ◽

D.А. Povalyaeva ◽

...

Keyword(s):

Disease Activity ◽

Macular Degeneration ◽

Pigment Epithelium ◽

Retinal Pigment ◽

Angiogenesis Inhibitor ◽

Morphological Parameters ◽

Complex Treatment ◽

Anti Vegf ◽

Purpose. To evaluate clinical efficacy of using nutraceutical "Resvega Forte" in complex treatment neovascular age-related macular degeneration (nAMD) against the background anti-VEGF therapy using ranibizumab (LUCENTIS®). Material and methods. The object of the study was 30 patients (30 eyes) with nAMD, who received 3 "loading" intravitreal injections (IVI) of 0,5 mg (0,05 ml) ranibizumab at intervals of 1 time per month, then within a year – by the protocol "Tread-and-Extend" with increase interval between injections by 2 weeks in the absence of disease activity and its reduction in case of resumption of activity. Patients of the 1st group (16 people) were supplemented with 3 "loading" IVI of ranibizumab with appointment of "Resvega Forte" complex for 3 months and then after 6 months. Patients of the 2nd group (14 people) did not receive "Resvega Forte" complex. To assess the effectiveness of treatment, in addition to standard methods, optical coherence tomography was performed with assessment of the central retinal thickness (CRT), the presence of detachment of the retinal pigment epithelium (RPE), retinal neuroepithelium (RNE), sub- and intraretinal fluid under PE. Results. By the 12th month of observation, none of the patients of the 1st group against the background of using two complexes "Resvega Forte" was found to have resumption of disease activity: the BCVA increased 3 times and amounted to 0,78±0,04, the average indexes of CRT corresponded to the norm (249,5±12,1 µm). The interval between injections increased to 12 weeks, and their total number was 7. In the 2nd group, the resumption of disease activity was noted twice, which was accompanied by decrease in the functional and morphological parameters of retina and required decrease in the intervals between injections to 10 weeks, which accordingly led to an increase in their number to 9-10. Conclusion. The inclusion of nutraceutical "Resvega Forte" in the treatment regimen of nAMD against the background of the therapy using angiogenesis inhibitor LUCENTIS® in the protocol "Tread-and-Extend" mode allows to reduce the risk of progression of nAMD, as well as to improve the functional and morphological parameters of retina. An integrated approach makes it possible to increase the interval between injections and reduce additional monitoring, which reduces the burden on both the patient and the doctor. Key words: neovascular age-related macular degeneration, aflibercept, nutraceuticals, "Resvega forte".