Subretinal Neovascularization Research Articles

Clinical and morphologic features of macular telangiectasia type 2: natural course of the disease

Purpose: The purpose of this study is to report the clinical characteristics of macular telangiectasia type 2 (MacTel 2) in a natural disease course. Materials and Methods: A retrospective analysis of patients diagnosed with MacTel 2 over a 4-year period. Best-corrected visual acuity (BCVA), fundus photography, and optical coherence tomography (OCT) images were reviewed. Differences in BCVA, fundoscopic findings, and OCT parameters were compared between the initial and final visits. Results: The study included 28 eyes from 14 patients (11 women, 3 males), with a mean age of 65.5 ± 9.8 years. The mean follow-up period was 55.6 ± 32.9 months. The mean BCVA at baseline and final follow-up were 0.51 ± 0.6 and 0.7 ± 0.62 logMAR, respectively. At the first and last visits, the right-angle venules were the most common fundoscopic finding (78.6% for both). Subretinal neovascularization (NV) was initially present in two eyes and developed in one eye during follow-up. The mean temporal macular thickness decreased significantly during the follow-up period, while the central and nasal thickness did not show a significant change. At the last visit, focal ellipsoid zone (EZ) loss was found in 27 eyes (96.4%), compared to 24 eyes (85.7%) at baseline. External limiting membrane (ELM) loss was found in 23 eyes (82.1%) at the first visit and in 25 eyes (89.3%) at the final visit. The increase in mean length of the EZ and ELM loss during the follow-up was not statistically significant. Conclusion: Despite the progressive effect of the disease on central visual acuity, it is very important to closely monitor these eyes for the development of secondary NV, which may develop due to degenerative and atrophic changes in the macula.

In vivo monitoring of active subretinal fibrosis in mice using collagen hybridizing peptides

Subretinal fibrosis is associated with worse visual outcomes in patients with neovascular age-related macular degeneration. As there is a lack of optimal biomarkers and no method that directly detects collagen in the back of the eye, novel tools that monitor fibrosis-related changes in neovascular age-related macular degeneration are needed. Here, using two mouse models (the laser-induced choroidal neovascularization model, and the JR5558 mouse presenting with spontaneous subretinal neovascularization with fibrosis), we imaged active fibrotic lesions using fluorescently labeled collagen hybridizing peptides (CHPs), short peptides that bind to single α-chain collagen structures during collagen remodeling. JR5558 retinal pigment epithelium/choroid flat mounts showed CHP co-staining with fibrosis and epithelial mesenchymal transition-related markers; additionally, CHP histopathology staining correlated with in vivo CHP imaging. After laser-induced choroidal neovascularization, in vivo CHP binding correlated with laser intensity, histopathology CHP and fibronectin staining. Laser-induced choroidal neovascularization showed decreased CHP intensity over time in healing/regressing versus active scars in vivo, whereas increased CHP binding correlated with elevated fibrosis in JR5558 mouse eyes with age. In bispecific angiopoietin 2/vascular endothelial growth factor antibody-treated JR5558 mice, CHPs detected significantly decreased collagen remodeling versus immunoglobulin G control. These results demonstrate the first use of CHPs to directly image remodeling collagen in the eye and as a potential clinical optical biomarker of active subretinal fibrosis associated with ocular neovascularization.

Diagnosing Macular Telangiectasia Type 2

MacTel type 2 is the most common subtype that results in atrophic changes and sometimes subretinal neovascularization (SRN). This case report will focus on a patient with MacTel type 2 and the management and treatment options pertinent to the case.

Clinical feature of cystoid macular degeneration in central serous chorioretinopathy.

Cystoid macular degeneration (CMD) is a feature of chronic central serous chorioretinopathy (CSCR). Present study intended to analyze the clinical presentation, risk factors, choroidal features, and outcome of CMD in CSCR. This was a retrospective, record-based descriptive study, which included chronic CSCR eyes with CMD. Demographic profile and clinical history were obtained from medical records. Spectralis spectral domain optical coherence tomography (SDOCT; Heidelberg Engineering,Germany) was used for acquiring SDOCT images and for performing fluorescein angiography , indocyanine green angiography , and optical coherence tomography (OCT) angiography. The study included 101 eyes of 69 consecutive patients of CSCR having CMD. The mean age of patients was 56 ± 9.4 years (range 40-79 years), and majority (63, 91.3%) of the patients were male. Prior history of corticosteroid use was present in seven (10.1%) patients. Mean time interval between the first diagnosis of CSCR and appearance of CMD was 55.3 ± 33.9 months. CMD was located away from the fovea in majority of eyes (68, 67.3%). Mean subfoveal choroidal thickness was 396.71 ± 90.5 μm. Subretinal pigment epithelium choroidal neovascularization was noted in four (3.96%) eyes. CMD appears as a late complication of CSCR and is usually present away from the fovea. Such eyes had thickened choroid and fewer cases had associated choroidal neovascularization. Further comparative studies would be needed to validate these findings.

Etiopathogensis of Macular Diseases in Terms of Glymphatic Fluid Circulation

This article is an analysis of theoretical aspects of etiopathogenesis of the macular zone of the eye in terms of glymphatic circulation of tissue fluid. To date, a lot of data has been accumulated on functional and structural changes of the macular zone in normal and in various pathologies. The genesis of macular edemas along with subretinal and choroidal neovascularisation could be highlighted and understood from a different point of view if assuming the presence of the glymphatic para- and perivascular fluid flow within the retina, channels in the vitreous body and the choroid. Clinical features of the various eye diseases including hereditary, highlight the paravascular glymphatic outflow routes. As a result of the data analysis, a new theory of disease development in the macular region has been developed for the first time, which explains the pathogenetic mechanisms of occurrence and progression of macular pathology based on the principles of glymphatic current.

Case Reports of Children with Vogt_Koyanagi_Harada Syndrome

Purpose: To assess the symptoms of Vogt-Koyanagi-Harada (VKH) syndrome in Moroccan children. Methods: Clinical data were acquired from the medical records of three children with VKH disease at the Marrakech University Children's Hospital. Results: Three cases fulfilled the VKH diagnostic criteria. The patients, ranging in age from 4 to 12 years, all had chronic illness. Uveitis was the most common ocular finding. Glaucoma, cataract, posterior synechiae, and subretinal neovascularization were complications for the patients. Conclusion: Depending on the long- term consequences, visual results were positive in all of the patients. VKH is uncommon in children, but it can be sight- threatening and requires close monitoring, making it an essential differential diagnosis.

Theory of macular diseases in terms of glymphatic fluid circulation

This article is an analysis of theoretical aspects of etiopathogenesis of the macular zone of the eye in terms of glymphatic circulation of tissue fluid. To date, a lot of data has been accumulated on functional and structural changes of the macular zone in normal and in various pathologies. The genesis of macular oedema along with subretinal and choroidal neovascularisation could be highlighted and understood from a different point of view if assuming the presence of the glymphatic para- and perivascular fluid flow within the retina, channels in the vitreous body and the choroid. Clinical features of the various eye diseases including hereditary, highlight the paravascular glymphatic outflow routes. The totality of data on various eye diseases, as well as the revealed clinical features of their course based on the latest scientific data and glymphatic flow in the nervous tissue allowed us to make assumptions about the presence of new physiological patterns of fluid flow in the posterior segment of the eye and formulate a new concept of pathogenesis of macular diseases.

High-Capacity Mesoporous Silica Nanocarriers of siRNA for Applications in Retinal Delivery.

The main cause of subretinal neovascularisation in wet age-related macular degeneration (AMD) is an abnormal expression in the retinal pigment epithelium (RPE) of the vascular endothelial growth factor (VEGF). Current approaches for the treatment of AMD present considerable issues that could be overcome by encapsulating anti-VEGF drugs in suitable nanocarriers, thus providing better penetration, higher retention times, and sustained release. In this work, the ability of large pore mesoporous silica nanoparticles (LP-MSNs) to transport and protect nucleic acid molecules is exploited to develop an innovative LP-MSN-based nanosystem for the topical administration of anti-VEGF siRNA molecules to RPE cells. siRNA is loaded into LP-MSN mesopores, while the external surface of the nanodevices is functionalised with polyethylenimine (PEI) chains that allow the controlled release of siRNA and promote endosomal escape to facilitate cytosolic delivery of the cargo. The successful results obtained for VEGF silencing in ARPE-19 RPE cells demonstrate that the designed nanodevice is suitable as an siRNA transporter.

Lost to follow-up of patients who received intravitreal anti-vascular endothelial growth factor therapy to treat four different retina disorders in an individual center in Brazil.

To identify risk factors for loss to follow-up in periodic intravitreal anti-vascular endothelial growth factor injections for the treatment patients with diabetic macular edema, subretinal neovascularization, age-related macular degeneration, and retinal vein occlusion in a single eye center in São Paulo, Brazil. This was a retrospective longitudinal study that gathered information from 992 patients who required intravitreal anti-vascular endothelial growth factor drugs over 6 months. The authors included age, eye disease, laterality, monthly income, distance, and payment mode as risk factors. Two hundred and seventy patients (29.93%) were lost to follow-up. Multivariate analysis showed age, monthly income, eye involvement, and type of medical assistance independently associated with loss to follow-up. The odds of loss to follow-up were greater among older patients than those less than 50 years (reference), p < 0.001. The odds of loss to follow-up were greater among patients who received unilateral treatment than those who received bilateral injections (p = 0.013). Concerning gross monthly income, there were no differences in the odds of the four salary strata; the data also indicate an absence of difference in the three strata of patients' distance to the clinic. Considering the diagnosis, only age-related macular degeneration showed greater odds of loss to follow-up (p = 0.016). Finally, the data suggest greater odds of loss to follow-up in private patients than in those on a health care plan (p < 0.001). Loss to follow-up is paramount because many patients may remain unassisted concerning their eye diseases. Identifying the risk factors is crucial to enforcing measures to increase adherence and the long-term success of the treatment.

Swept source optical coherence tomography and optical coherence tomography angiography for diagnosis and follow‐up of type 2 macular telangiectasia

AbstractPurpose: To report the contribution of swept source optical coherence tomography (SS‐OCT) and OCT‐angiography (OCTA) imaging findings in the diagnosis and the follow‐up of type 2 macular telangiectasia (MacTel 2).Methods: A retrospective study of eight eyes (five patients) with various stages of MacTel2. Clinical staging of MacTel 2 was performed based on SS‐OCT and OCTA.Results: The average age was 63 years old. The mean follow up was 33.6 months. A very early non‐proliferative stage was found in three eyes, an early non‐proliferative stage in three eyes and a late proliferative stage in two eyes. The most common findings on SS‐OCT were disruption of the inner segment‐outer segment (IS/OS) layer in all eyes, parafoveal hyporeflective retinal cavities in four eyes and superficial retinal crystals in three eyes. Two eyes showed irregularity of foveal contour and internal limiting membrane draping associated with retinal vascular channels connecting the superficial and deep retinal layers and forming retinal‐choroidal anastomosis. OCTA findings included capillary telangiectatic changes and enlargement of intercapillary spaces predominantly in deep capillary plexus (DCP) in comparison with superficial capillary plexus (SCP) in all eyes. Irregularity of capillary size in the perifoveal region of the DCP and SCP, predominantly temporal to the fovea, was found in five eyes. Circumferential capillary distortions and subretinal neovascularization at the level of the outer retina and choriocapillaris were detectable in two eyes. At the mean period of follow‐up, lesions were stable in two eyes, an extension of IS/OS disruption was noted in four eyes, parafoveal cavities' appearance and/or extension was found in two eyes and neovascular proliferation appeared in one eye.Conclusions: SS‐OCT and OCTA imaging features facilitate the diagnosis, staging and long‐term follow‐ up of MacTel 2. Further prospective studies are need to characterize the progressive and sequential nature of structural changes in this disease.

EFFECTS OF HALF-DOSE PHOTODYNAMIC THERAPY ON CHRONIC CENTRAL SEROUS CHORIORETINOPATHY WITH OR WITHOUT MACULAR NEOVASCULARIZATION ASSESSED USING OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY.

To assess the effects of half-dose photodynamic therapy on subretinal fluid and macular neovascularization (MNV) using optical coherence tomography angiography in patients with chronic central serous chorioretinopathy. Clinical information on 168 patients (168 eyes) with chronic central serous chorioretinopathy obtained before and 6 months after treatment with half-dose photodynamic therapy was retrospectively analyzed. Patients were categorized into a success (145 eyes) or failure (23 eyes) group based on the absence or presence of subretinal fluid, respectively, and clinical data were compared between them. Macular neovascularization was studied in 147 cases with available optical coherence tomography angiography images. P < 0.05 indicated statistical significance. The success group showed a younger patient age, better posttreatment best-corrected visual acuity, and thicker pretreatment central choroidal thickness (all, P < 0.047) than did the failure group. Regarding MNV analysis, nine, eight, and 130 eyes had definite, possible, and no MNV, respectively, at baseline; among them, 100.0%, 75.0%, and 2.3%, respectively, had MNV at 6 months posttreatment. Patients with definite MNV at baseline were less likely to show successful subretinal fluid resolution. Although half-dose photodynamic therapy is generally effective for the treatment of chronic central serous chorioretinopathy, coexisting MNV may compromise the outcome; thus, optical coherence tomography angiography-based assessment of chronic central serous chorioretinopathy is important.

Pachychoroid Disease

Pachychoroid spectrum disorders include uncomplicated pachychoroid, pachychoroid pigment epitheliopathy, central serous chorioretinopathy, pachychoroid neovasculopathy, polypoidal choroidal vasculopathy/aneurysmal type 1 neovascularisation, focal choroidal excavation and peripapillary pachychoroid syndrome. They are characterized by a thickened and hyperpermeable choroid and thinning of the choriocapillaris. The disorders are being diagnosed with increasing frequency and differentiation due to the advancement of multimodality imaging. Current understanding of the development, course, possible complications and treatment of these diseases is growing rapidly, but not all mechanisms have yet been elucidated. A correct diagnosis is important, especially the differentiation between the presence of active neovascularisation or a purely exudative stage, in order to initiate a therapy. It is also not yet clear why patients have a thickened choroid and why some of these patients develop pathological changes such as subretinal fluid, RPE changes or neovascularisation.

Лечение хориоидальной неоваскуляризации, ассоциированной с друзами диска зрительного нерва

Purpose. To describe a rare clinical case of bilateral choroidal neovascularization (CNV) associated with optic nerve head (ONH) drusen and to report a positive functional and clinical outcome of intravitreal injections of vascular endothelial growth factor inhibitors (anti-VEGF) in this patient. Material and methods. A 39-year-old man with ONH drusen complained of decreased visual acuity and distortion of objects. During the examination, the bilateral CNV was detected in peripapillary area. The patient received two consecutive intravitreal injections of anti-VEGF in the right eye and one injection in the left eye. Results. After the treatment, reabsorption of subretinal fluid and an increase of visual acuity were observed. There were no complications associated with injections. The best-corrected visual acuity remains stabilized at 20/20 at three years of followup. According to the optical coherence tomography parameters, there was no negative dynamics of CNV. Conclusion. ONH drusen may cause several complications, including the development of CNV and significant decrease in visual acuity, due to the CNV progression. Follow-up of patients with ONH drusen is necessary for early diagnosis and treatment of complications. The differential sign of CNV associated with ONH drusen is a localization in the peripapillary area nasal to the fovea. A search of the literature revealed only a few publications on the use of anti-VEGF in patients with CNV associated with ONH drusen. This method was effective and demonstrated positive functional and clinical outcome in the presented clinical case. Key word: subretinal neovascularization; choroidal neovascularization; optic nerve head drusen; optical coherence tomography; antivascular endothelial growth factor therapy

Macular Telangiectasia Type 2: A Comprehensive Review.

Macular telangiectasia Type 2 (MacTel) is a gradually progressive disease that affects the quality of life by impairing both distant and near vision. It had previously been considered a vascular condition, but recent evidence suggests a neurodegenerative etiology, with primary involvement of Muller cells. Retinal pigment epithelium (RPE) hyperplasia and subretinal neovascularization (SNV) are responsible for most of the vision loss in advanced cases. Neurotrophic factors in the non-proliferative phase and intravitreal anti-Vascular Endothelial growth factor (VEGF) in the proliferative phase have shown to retard the progression of the disease. This review will discuss the pathophysiology, clinical features, important diagnostic imaging studies and available treatment options for MacTel.

Angiopoietin-1 Is Required for Vortex Vein and Choriocapillaris Development in Mice.

The choroidal vasculature, including the choriocapillaris and vortex veins, is essential for providing nutrients to the metabolically demanding photoreceptors and retinal pigment epithelium. Choroidal vascular dysfunction leads to vision loss and is associated with age-related macular degeneration and the poorly understood pachychoroid diseases including central serous chorioretinopathy and polypoidal choroidal vasculopathy that are characterized by formation of dilated pachyvessels throughout the choroid. Using neural crest-specific Angpt1 knockout mice, we show that Angiopoietin 1, a ligand of the endothelial receptor TEK (also known as Tie2) is essential for choriocapillaris development and vortex vein patterning. Lacking choroidal ANGPT1, neural crest-specific Angpt1 knockout eyes exhibited marked choriocapillaris attenuation and 50% reduction in number of vortex veins, with only 2 vortex veins present in the majority of eyes. Shortly after birth, dilated choroidal vessels resembling human pachyvessels were observed extending from the remaining vortex veins and displacing the choriocapillaris, leading to retinal pigment epithelium dysfunction and subretinal neovascularization similar to that seen in pachychoroid disease. Together, these findings identify a new role for ANGPT1 in ocular vascular development and demonstrate a clear link between vortex vein dysfunction, pachyvessel formation, and disease.

Henle Fiber Layer Hemorrhage in Macular Telangiectasia Type 2: Is Right Eye Dominance Coincidence or Consequence?

To summarize all reported cases of Henle fiber layer (HFL) hemorrhage in the absence of subretinal neovascularization (SRNV) in patients with macular telangiectasia type 2 (MacTel2) and to propose a mechanism for the right-sided predominance of this unique presentation. Perspective. Collection, review, and analysis of all cases in the literature and in the authors' databases of HFL hemorrhage in MacTel2, including analysis of baseline and follow-up multimodal retinal imaging findings of selected cases. Elucidation of the complex interplay of systemic venous pressure with the deep retinal capillary plexus and hypothesis regarding the right-sided predilection of HFL hemorrhage complicating MacTel2. Ten patients presented with a unilateral, characteristic radial macular hemorrhage within the HFL that affected only the right eye in all cases. Absence of SRNV was confirmed by fluorescein angiography and/or optical coherence tomography angiography. The hemorrhage resolved spontaneously in at least 7 of the 10 eyes. The HFL hemorrhage may plausibly be explained by dysfunction of the deep capillary plexus in MacTel2 combined with an acute rise in central venous pressure, for which the right side may be at increased risk. HFL hemorrhage can complicate MacTel2 in the absence of SRNV, and the radial pattern of blood affecting only the right eye is remarkable. The right eye predominance may be multifactorial in etiology. Related factors may include the right-sided predilection of MacTel2 and/or increased right-sided dural sinus drainage related to normal anatomical variation.

Permeability, anti-inflammatory and anti-VEGF profiles of steroidal-loaded cationic nanoemulsions in retinal pigment epithelial cells under oxidative stress

Age-related macular degeneration (AMD) is defined as a degenerative, progressive and multifactorial disorder that affects the macula with a complex etiology. The retinal pigment epithelium is a monolayer of cells that has the function to separate the surface of the choroid from the neural retina that is involved in the signal transduction leading to vision. The blood-aqueous barrier and the blood retinal barrier limit the permeation of drugs into the retina and thereby reducing their efficacy. Triamcinolone acetonide (TA) is widely used as anti-inflammatory and immunomodulatory drug that promotes the inhibition of the inflammatory processes. The factors that stimulate or inhibit angiogenesis in AMD create a local balance that is responsible for the growth of sub-retinal neovascularization. In AMD, the main angiogenic stimulus is the vascular endothelial growth factor (VEGF). In this work, nanoemulsions with cationic surfactants (mono- and dicationic DABCO and quinuclidine) were produced to deliver TA, and were found to reduce the production of tumor necrosis factor alpha (TNF-α), which stimulates the choroidal neovascularization development by upregulating the VEGF production, and consequently decreased the VEGF levels. Our results support the potential use of mono- and dicationic DABCO and quinuclidine-based cationic nanoemulsions for the delivery of TA in the treatment of AMD.

Application of Optical Coherence Tomography to a Mouse Model of Retinopathy.

Optical coherence tomography (OCT) offers a noninvasive method for the diagnosis of retinopathy. The OCT machine can capture retinal crosssectional images from which the retinal thickness can be calculated. Although OCT is widely used in clinical practice, its application in basic research is not as prevalent, especially in small animals such as mice. Because of the small size of their eyeballs, it is challenging to conduct fundus imaging examinations in mice. Therefore, a specialized retinal imaging system is required to accommodate OCT imaging on small animals. This article demonstrates a small-animal-specific system for OCT examination procedures and a detailed method for image analysis. The results of retinal OCT examination of very-low-density lipoprotein receptor (Vldlr) knockout mice and C57BL/6J mice are presented. The OCT images of C57BL/6J mice showed retinal layers, while those of Vldlr knockout mice showed subretinal neovascularization and retinal thinning. In summary, OCT examination could facilitate the noninvasive detection and measurement of retinopathy in mouse models.

Inhibition of ocular neovascularization by novel anti-angiogenic compound

Aberrant angiogenesis lies at the heart of a wide range of ocular pathologies such as proliferative diabetic retinopathy, wet age-related macular degeneration and retinopathy of prematurity. This study explores the anti-angiogenic activity of a novel small molecule investigative compound capable of inhibiting profilin1-actin interaction recently identified by our group. We demonstrate that our compound is capable of inhibiting migration, proliferation and angiogenic activity of microvascular endothelial cells in vitro as well as choroidal neovascularization (CNV) ex vivo. In mouse model of laser-injury induced CNV, intravitreal administration of this compound diminishes sub-retinal neovascularization. Finally, our preliminary structure-activity relationship study (SAR) demonstrates that this small molecule compound is amenable to improvement in biological activity through structural modifications.

Side Effects of Brolucizumab.

Age-related macular degeneration and its complication, subretinal neovascularization, are common causes of progressive, irreversible impairment of central vision. Anti-vascular endothelial growth factor (anti-VEGF) therapy has improved the visual outcome and provided an evolution in the treatment of retinal disease. The current four anti-VEGF drugs – pegaptanib, ranibizumab, aflibercept, and bevacizumab – have been administered for many years. A new anti-VEGF agent, brolucizumab, was approved by the U.S. Food and Drug Administration (FDA) in late 2019 for the treatment of wet age-related macular degeneration. Brolucizumab is a novel single-chain fragment variable antibody that inhibits all isoforms of VEGF-A and has been suggested to have more tissue penetration. Despite all the benefits, there are some reports of serious side effects that need to be understood in managing patients. Brolucizumab has been reported to cause occlusive retinal vasculitis in the setting of intraocular inflammation, which has not been seen in other anti-VEGF medications. A PubMed and Scopus search was performed and all article types were included. In the present article, we have reviewed the reported side effects of brolucizumab.