The Asia-Pacific Journal of Ophthalmology

  • January/February 2018 - Volume 7 - Issue 1
    pp: 1-67
    Special Issue on Retinal Vascular Diseases including Vascular Occlusions and Diabetic Retinopathy
    Guest Editors-in-Chief: Suber Huang, Lihteh Wu


Retinal Vascular Diseases in the Asia-Pacific: Shifting Paradigms for Management Huang, Suber S.; Wu, Lihteh
This special issue of the Asia-Pacific Journal of Ophthalmology is dedicated to reviewing recent advances in the management of retinal vascular diseases. Collectively, retinal vascular diseases account for the great majority of blinding retinal diseases in the world. Insights and controversies in the diagnosis and treatment of diabetic retinopathy, vein occlusion, retinopathy of prematurity, and challenges unique to the Asia-Pacific are addressed. The rapidly increasing burden of treatment of these conditions is accelerating even as knowledge, technology, and the socioeconomic status of the Asia-Pacific grow at a historic pace. This issue examines the opportunities that may exist to create systems of successful and efficient care.

Review Article

Diabetic Retinopathy in the Asia-Pacific Chua, Jacqueline; Lim, Claire Xin Ying; Wong, Tien Yin; Sabanayagam, Charumathi
Diabetic retinopathy (DR), the most common complication of diabetes mellitus, is the leading cause of new cases of blindness in middle-aged and elderly in the Asia-Pacific. It has been estimated that 51% of all those with blindness due to DR globally (n = 424,400) and 56% of those with visual impairment due to DR (2.1 million) come from the Asia-Pacific. Prevalence of DR among those with diabetes ranged from 10% in India to 43% in Indonesia within the Asia-Pacific. Awareness of DR among persons with diabetes ranged from 28% to 84%. Most common modifiable risk factors for DR in the Asia-Pacific were hyperglycemia, blood pressure, dyslipidemia, and obesity. Implementation of systematic screening programs for DR and advancement in telemedicine screening methods have increased patient coverage and cost-effectiveness, though there are still numerous factors impeding screening uptake in the low-middle income regions of the Asia-Pacific. Management and treatment of DR in the Asia-Pacific is mainly limited to traditional laser retinopexy, but it is suboptimal despite new clinical approaches such as use of intravitreal anti.vascular endothelial growth factor and steroids due to limited resources. Further research and data are required to structure a more cost-effective public healthcare program and more awareness-building initiatives to increase the effectiveness of DR screening programs.
The Role of Teleophthalmology in the Management of Diabetic Retinopathy Salongcay, Recivall P.; Silva, Paolo S.
The emergence of diabetes as a global epidemic is accompanied by the rise in diabetes‑related retinal complications. Diabetic retinopathy, if left undetected and untreated, can lead to severe visual impairment and affect an individual's productivity and quality of life. Globally, diabetic retinopathy remains one of the leading causes of visual loss in the working‑age population. Teleophthalmology for diabetic retinopathy is an innovative means of retinal evaluation that allows identification of eyes at risk for visual loss, thereby preserving vision and decreasing the overall burden to the health care system. Numerous studies worldwide have found teleophthalmology to be a reliable and cost‑efficient alternative to traditional clinical examinations. It has reduced barriers to access to specialized eye care in both rural and urban communities. In teleophthalmology applications for diabetic retinopathy, it is critical that standardized protocols in image acquisition and evaluation are used to ensure low image ungradable rates and maintain the quality of images taken. Innovative imaging technology such as ultrawide field imaging has the potential to provide significant benefit with integration into teleophthalmology programs. Teleophthalmology programs for diabetic retinopathy rely on a comprehensive and multidisciplinary approach with partnerships across specialties and health care professionals to attain wider acceptability and allow evidence‑based eye care to reach a much broader population.
Multimodality Imaging in Diabetic Macular Edema Acón, Dhariana; Wu, Lihteh
Throughout ophthalmic history it has been shown that progress has gone hand in hand with technological breakthroughs. In the past, fluorescein angiography and fundus photographs were the most commonly used imaging modalities in the management of diabetic macular edema (DME). Today, despite the moderate correlation between macular thickness and functional outcomes, spectral domain optical coherence tomography (SD-OCT) has become the DME workhorse in clinical practice. Several SD-OCT biomarkers have been looked at including presence of epiretinal membrane, vitreomacular adhesion, disorganization of the inner retinal layers, central macular thickness, integrity of the ellipsoid layer, and subretinal fluid, among others. Emerging imaging modalities include fundus autofluorescence, macular pigment optical density, fluorescence lifetime imaging ophthalmoscopy, OCT angiography, and adaptive optics. Technological advances in imaging of the posterior segment of the eye have enabled ophthalmologists to develop hypotheses about pathological mechanisms of disease, monitor disease progression, and assess response to treatment. Spectral domain OCT is the most commonly performed imaging modality in the management of DME. However, reliable biomarkers have yet to be identified. Machine learning may provide treatment algorithms based on multimodal imaging.
Diabetic Macular Edema: Current Understanding, Pharmacologic Treatment Options, and Developing Therapies Miller, Kevin; Fortun, Jorge A.
Diabetic retinopathy and diabetic macular edema comprise a major source of visual disability throughout the developed world. The etiology and pathogenesis of macular edema is intricate and multifactorial, in which the hyperglycemic state in diabetes induces a microangiopathy. Through several inflammatory and vasogenic mediators, including vascular endothelial growth factor (VEGF) upregulation and inflammatory cytokines and chemokines, pathologic changes are induced in the vascular endothelium triggering breakdown of the blood retinal barrier, causing extravasation of fluid into the extracellular space and manifesting clinically as macular edema, resulting in visual loss. The advent of medications targeting the VEGF pathway has led to great clinical improvements compared with the previous standard of care of laser therapy alone, as shown in studies such as RISE, RIDE, VIVID, VISTA, and DRCR. However, analyses have shown that many patients have inadequate response or are nonresponders to anti-VEGF therapy, demonstrating the need for additional therapies to more comprehensively treat this disease. Although corticosteroid treatments and implants have demonstrated some efficacy in adjunctive and supplemental treatment, the need to more adequately treat macular edema remains. Our knowledge of diabetic macular edema continues to grow, leading to new currently available and emerging pharmacotherapies to further enhance our treatment and restore vision in those affected by diabetic macular edema. This review will discuss the pathogenesis of diabetic macular edema and the pharmacologic therapies available for its treatment, including anti-VEGF, steroids, and newer therapies still in development, such as angiopoietin antagonists, Tie2 agonists, kallikrein inhibitors, interleukin inhibitors, and others.
Intravitreal Bevacizumab in Diabetic Retinopathy Recommendations from the Pan-American Collaborative Retina Study Group (PACORES): The 2016 Knobloch Lecture Arevalo, J. Fernando; Liu, T.Y. Alvin; Pan-American Collaborative Retina Study Group (PACORES)
The advent of intravitreal anti-vascular endothelial growth factor (anti-VEGF) medications has revolutionized the treatment of diabetic eye diseases. Herein, we report the outcomes of clinical studies carried out by the Pan-American Collaborative Retina Study Group (PACORES), with a specific focus on the efficacy of intravitreal bevacizumab in the management of diabetic macular edema and proliferative diabetic retinopathy. We will also discuss the use of intravitreal bevacizumab as a preoperative, adjuvant therapy before vitrectomy for proliferative diabetic retinopathy.
Retinal Vein Occlusion Review Ip, Michael; Hendrick, Andrew
Retinal vein occlusions are a very common condition with great importance in ophthalmology clinical practice. This article reviews the salient epidemiology, risk factors, clinical features, and treatments related to retinal vein occlusions.
Use of OCTA, FA, and Ultra-Widefield Imaging in Quantifying Retinal Ischemia: A Review Or, Chris; Sabrosa, Almyr S.; Sorour, Osama; Arya, Malvika; Waheed, Nadia
As ischemia remains a key prognostic factor in the management of various diseases including diabetic retinopathy, an increasing amount of research has been dedicated to its quantification as a potential biomarker. Advancements in the quantification of retinal ischemia have been made with the imaging modalities of fluorescein angiography (FA), ultra-widefield imaging (UWF), and optical coherence tomography angiography (OCTA), with each imaging modality offering certain benefits over the others. FA remains the gold standard in assessing the extent of ischemia. UWF imaging has allowed for the assessment of peripheral ischemia via FA. It is, however, OCTA that offers the best visualization of retinal vasculature with its noninvasive depth-resolved imaging and therefore has the potential to become a mainstay in the assessment of retinal ischemia. The primary purpose of this article is to review the use of FA, UWF, and OCTA to quantify retinal ischemia and the various methods described in the literature by which this is achieved.
Telemedicine for ROP Shah, Parag K.; Ramya, Appanraj; Narendran, Venkatapathy
With the increasing survival of preterm babies in the Asia-Pacific region, there has been an increase in the incidence of retinopathy of prematurity (ROP). There is also a lack of trained ophthalmologists to screen for this disease. New strategies for screening of ROP are required, wherein the load on the ophthalmologist can be reduced. Telemedicine is an excellent tool to address this need. This paper reviews the initial studies comparing digital imaging with indirect ophthalmoscopy, the current active ROP telescreening programs in the world, and ends with studies dealing with automated diagnosis of ROP.
Management of Retinopathy of Prematurity—Use of Anti-VEGF Therapy Tran, Kimberly D.; Cernichiaro-Espinosa, Linda A.; Berrocal, Audina M.
Retinopathy of prematurity (ROP) is a leading cause of childhood blindness worldwide. Although laser photocoagulation re-mains the gold standard for treating threshold and prethreshold disease (type 1 ROP), the off-label use of anti‒vascular endothelial growth factor (anti-VEGF) therapy to treat ROP is increasing. Benefits include acute regression of ROP, growth of retinal vasculature beyond the demarcation line, lesser degree of myopia and peripheral visual field loss, and avoidance of sedation and intubation required for laser. However, controversies regarding anti-VEGF in this vulnerable population persist including choice of anti-VEGF agent, dosing, systemic absorption, safety, and late recurrence. This review updates recent evidence regarding the use of anti-VEGF therapy in the management of ROP.
Anti-VEGF Agents and the Risk of Arteriothrombotic Events Zarbin, Marco A.
Blockade of vascular endothelial growth factor (VEGF) signaling, whether via sequestration of free VEGF or via inhibition of the tyrosine kinases activated by VEGF, is associated with decreased nitric oxide (NO) and prostaglandin-I 2 (PG-I 2) production along with vascular endothelial cell death. Systemic administration of drugs that block VEGF signaling (eg, for cancer treatment) is associated with systemic complications such as hypertension and thrombosis. Evidence regarding the risk of systemic serious adverse events after intravitreal injection of anti-VEGF agents in patients with diabetic macular edema or neovascular age-related macular degeneration is inconsistent, in part because of study design limitations (eg, bias of ascertainment through strict enrollment criteria and/or inadequate power to identify the risk of low frequency events). Studies involving patients at high risk of arteriothrombotic events (eg, patients with diabetic macular edema) who have high exposure to intravitreal anti-VEGF therapy (eg, monthly aflibercept or ranibizumab injec-tion) demonstrate an increased risk of all-cause mortality compared with randomized controls. The pharmacokinetics of anti-VEGF drug clearance from the systemic circulation and the documented sustained reduction in free plasma VEGF levels after intravitreal aflibercept and bevacizumab injection are consistent with these findings. Although the frequency of systemic serious adverse events after intravitreal anti-VEGF therapy is low, some patients may be at higher risk (eg, those with recent stroke or multiple strokes), and physicians may wish to take special measures with these patients to minimize the risk of systemic complications.
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