Abstract: Pathologic myopia is the major cause of the loss of the best-corrected visual acuity (BCVA) worldwide, especially in East Asian countries. The loss of BCVA is caused by the development of myopic macula patchy, myopic traction macula patchy, and myopic optic neuropathy (or glaucoma). The development of such vision-threatening complications is caused by eye deformity, characterized by a formation of posterior staphyloma. The recent advance in ocular imaging has greatly facilitated the clarification of pathologies and pathogenesis of pathological myopia and myopia-related complications. These technologies include ultra-wide field fundus imaging, swept-source optical coherence tomography, and 3D MRI. In addition, the new treatments such as anti-VEGF therapies for myopic choroid all neovascularization have improved the outcome of the patients. Swept-source OCT showed that some of the lesions of myopic maculopathy were not simply chorioretinal atrophy but were Bruch’s membrane holes. Features of myopic traction maculopathy have been analyzed extensively by using OCT. The understanding the pathophysiology of complications of pathologic myopia is considered useful for better management of this blinding eye disease.

Keywords: Diabetic macular edema (DME); diabetic macular oedema (DMO); anti-vascular endothelial growth factor (anti-VEGF); laser photocoagulation; randomised clinical trials (RCTs); retina; diabetic retinopathy

Abstract: To describe the current aging population in China and globally, especially as it applies to age-related macular degeneration (AMD). To review the current standards of care for treating both wet (exudative) eAMD and dry (atrophic) aAMD. And to introduce a model for experimentation that is based on the Age-Related Eye Disease Study (AREDS) using eye bank tissue. A literature search that outlines current aging populations, standards of clinical treatment as defined by large, multicenter, randomized clinical trials that present level-I data with a low risk for bias. An experimental model system of AMD is presented that enables scientific analysis of AMD pathogenesis by applying grading criteria from the AREDS to human eye bank eyes. Analysis includes proteomic, cellular, and functional genomics. The standard of care for the treatment of eAMD is currently defined by the use of several anti-vascular endothelial growth (anti-VEGF) agents alone or in combination with photodynamic therapy. Monotherapy treatment intervals may be monthly, as needed, or by using a treat-and-extend (TAE) protocol. There are no proven therapies for aAMD. AMD that is phenotypically defined at AREDS level 3, should be managed with the use of anti-oxidant vitamins, lutein/zeaxanthin and zinc (AREDS-2 formulation). By understanding the multiple etiologies in the pathogenesis of AMD (i.e., oxidative stress, inflammation, and genetics), the use of human eye bank tissues graded according to the Minnesota Grading System (MGS) will enable future insights into the pathogenesis of AMD. Initial AMD management is with lifestyle modification such as avoiding smoking, eating a healthy diet and using appropriate vitamin supplements (AREDS-2). For eAMD, anti-VEGF therapies using either pro re nata (PRN) or TAE protocols are recommended, with photodynamic therapy in appropriate cases. New cellular information will direct future, potential therapies and these will originate from experimental models, such as the proposed eye bank model using the MGS, that leverages the prospective AREDS database.

Background: To investigate the effect of sirolimus (SRL) eye drops on acute alkali-burn-induced corneal neovascularization (CNV) and explore its possible mechanism.

Methods: A total of 57 male Sprague-Dawley rats weighing 160–180 g were randomly divided into four groups including a normal control group (NC group, n=12), an untreated alkali-burned model control group (MC group, n=15), a blank eye drop treatment group (BT group, n=15), and an SRL eye drop treatment group (ST group, n=15). Corneal inflammation and CNV were observed and scored under a slit-lamp microscope 3, 7, and 14 days after alkali exposure. Three rats were randomly sacrificed in each group before modeling and 3, 7, 14 days after modeling, and the corneas of right eyes were harvested for Western blotting to compare the expression levels of VEGFR2 and caspase-3.

Results: Corneal inflammation scoring showed that the corneal edema and conjunctival congestion were severe in the MC, BT, and ST groups 1 day after alkali exposure but were alleviated at day 3. The corneal transparency was significantly higher in the ST group than in the MC and BT groups at days 7 (F=9.77, P<0.05) and 14 (F=5.81, P<0.05). At day 1, the corneal limbal vascular network was markedly filled. SNV was obvious at days 3, 7, and 14. The new blood vessels were shorter and sparser in the ST group than in the MC and BT groups, and the CNV scores showed significant differences among these groups (day 3: F=8.60, P<0.05; day 7: F=11.40, P<0.05; and day 14: F=41.59, P<0.01). Western blotting showed that the expressions of VEGFR2 and caspase-3 were low before modeling and showed no significant difference among the different groups (F=0.52, P>0.05; F=0.98, P>0.05). The corneal expression of VEGFR2 became significantly higher in the MC and BT groups than in the ST group 3, 7, and 14 days after alkali exposure, and there were significant differences in relative gray-scale values among these groups (day 3: F=32.16, P<0.01; day 7: F=85.96, P<0.01; day 14: F=57.68, P<0.01). The increase in the corneal expression of caspase-3 was significantly larger in the ST group than in the MC and BT groups at days 3, 7, and 14, and there were significant differences in relative gray-scale values among groups (day 3: F=32.16, P<0.01; day 7: F=53.02, P<0.01; day 14: F=38.67, P<0.01).

Conclusions: SRL eye drops can alleviate acute alkali-burn-induced corneal inflammation and inhibit alkali-burn-induced CNV in rat models. It can reduce VEGFR2 expression and increase caspase-3 expression in the corneal tissue, which may contribute to the inhibition of alkali-burn-induced CNV.

Abstract: Age-related macular degeneration (ARMD), one of the most common causes of blindness, should be considered more due to its exponential increase in the coming 20 years as a result of increasing the age of the population. Whereas more recent studies offered newer scaling systems for ARMD, traditionally it is classified as the early and late stages. The main injury in this disease occurred in retinal pigment epithelium (RPE) and the retina. RPE cells have a crucial role in hemostasis and supporting photoreceptors. In the early stages, damages to RPE are minimal and mainly no treatment is needed because most patients are asymptomatic. However, in the late stages, RPE impairment may lead to the invasion of choroidal vessels into the retina. Although anti-angiogenic agents can inhibit this abnormal growth of blood vessels, they cannot stop it completely, and finally, total loss of retinal cells may occur (geographical atrophy). Since this prevalent disease has not had any cure yet, the concept of substituting the RPE cells should be considered. Repairing the injury to central nervous system cells is almost impossible because the regenerative capacity of these cells is limited. Recently, the use of regenerative substitutes has been suggested to replace damaged tissues. Amniotic membrane (AM) has been raised as a suitable substitute for damaged RPE cells due to all of its unique properties: pluripotency, anti-angiogenic effect, and anti-inflammatory effect. Based on the few studies that have been published so far, it seems that the use of this membrane in the treatment of ARMD can be helpful, but more studies are needed.

Abstract: Age-related macular degeneration (AMD) remains a leading cause of severe visual impairment in developing countries. Although dry-type AMD and geographic atrophy (GA) are progressive conditions with the associated decrease of visual functions, no well-established treatment regimen was proposed for the disease. Wet-type AMD is effectively treated with intravitreal anti-angiogenic agents, but frequent injections are a major issue for the affected patients. Recent advances in AMD genetics have provided new insights into the pathogenesis and novel therapeutic targets of AMD, but the benefits of using genetic testing and genotype-based risk models for AMD development and progression still lacks evidence. Novel AMD treatments aim to increase the interval among intravitreal injections through new therapeutic agents and modern delivery devices. Simultaneously, gene therapy for dry and wet AMD is widely studied. Although gene therapy possesses a major superiority over other novel treatments regarding a persistent cure of disease, many challenges exist in the way of its broad impact on the ocular health of AMD patients.

Abstract: Macular neovascularization (MNV) is the hallmark of neovascular age-related macular degeneration (nAMD), one of the leading causes of vision loss in the developed world. The current MNV standard of care including frequent intravitreal anti-vascular endothelial growth factor (VEGF) injections, although has revolutionized favorably the treatment, places a substantial burden on patients, caregivers, and physicians. Brolucizumab is a newly developed single-chain antibody fragment that inhibits activation of VEGF receptor 2 with in vitro affinity and potency comparable to commercially-available anti-VEGF agents. Its small molecular weight and its design allow for high solubility and retinal tissue penetration, and improve bynding affinity to the target. Also a high clearance rate leading to minimal systemic exposure was observed. Brolucizumab has shown similar gains in visual acuity compared with other anti-VEGF molecules but a higher and earlier resolution of nAMD related fluid, achieving sustained macular dryness with longer mantainance injection interval ranging from 8 to 12 weeks after monthly loading doses. Rare cases of ocular inflammation also including retinal vasculitis and retinal vascular occlusions referred to an immune-mediated reaction posed safety concerns on selected patients and mantainance treatment interval shorter than 8 weeks.The present review summarizes several key points including the molecular structure and pharmacokinetics, the preclinical and clinical evidence of brolucizumab administration evaluating its efficacy, tolerability, and safety, extended dosing regimens and other indications still under clinical investigation.

Abstract: Age-related macular degeneration (AMD) is a leading cause of blindness worldwide. AMD most commonly affects older individuals and is characterized by irreversible degeneration of the retinal pigment epithelium and neurosensory retina. Currently, there are limited treatment options for dry AMD outside of lifestyle modification and nutrient supplementation. Risuteganib [Luminate (ALG-1001), Allegro Ophthalmics, CA, USA] is an intravitreally administered inhibitor of integrin heterodimers αVβ3, αVβ5, α5β1, and αMβ2. It is currently undergoing clinical trials for the treatment of dry AMD and diabetic macular edema (DME). Preclinical studies have shown that risuteganib has an effect on the pathways for angiogenesis, inflammation, and vascular permeability. Ongoing clinical trials have had promising results showing improvements in patient best corrected visual acuity (BCVA) and reduced central macular thickness measured by optical coherence tomography (OCT). There is a pressing need for treatments for dry AMD and while risuteganib appears to have a potential benefit for patients, more data are needed before one can truly evaluate its efficacy. This narrative review provides a concise summary of the most up to date data regarding the proposed mechanism of action of risuteganib in the treatment of nonexudative AMD and DME as well as the results from recent phase 1 and phase 2 clinical trials.

Abstract: In developed countries, age-related macular degeneration (AMD) is the main cause of visual impairment in the elderly. Though the etiology of AMD is still unclear, it has been well understood that vascular endothelial growth factor (VEGF) is involved in the development of aberrant vasculature that represents the neovascular AMD (nAMD). Hence, VEGF inhibition is a more effective way to control nAMD. Pegaptanib, ranibizumab, and aflibercept are three drugs approved by the US Food and Drug Administration (FDA) to treat nAMD. Bevacizumab (an anti-VEGF medication comparable to ranibizumab) is already widely used off label. Existing anti-VEGF medicines are made up of antibodies or pieces of antibodies. Synthetic designed ankyrin repeat proteins (DARPins) imitate antibodies introduced recently by evolutions in bioengineering technology. These agents are designed to have high specificity and affinity to a specific target, smaller molecular size, and better tissue penetration, making them more stable and longer-acting at less concentration. Abicipar pegol (Allergan, Dublin, Ireland) is a DARPin that interlocks all VEGF-A isoforms. It has a greater affinity for VEGF and a longer intraocular half-life than ranibizumab, making it a feasible anti-VEGF agent. This review describes the properties and efficacy of abicipar, the new anti-VEGF agent, in clinical practice, which aims to improve outcomes, safety, and treatment burden of nAMD.