The Asia-Pacific Journal of Ophthalmology

  • January/February 2016 - Volume 5 - Issue 1
    pp: 1-92
    Special Issue on Glaucoma
    Guest Editor-in-Chief: Robert Ritch
    Guest Editors: Jost Jonas, Christopher Leung, Ki-Ho Park,
    Arthur Sit



Glaucoma: Today and Tomorrow Lam, Dennis; Lee, Jacky; Jonas, Jost; Leung, Christopher; Park, Ki-Ho; Sit, Arthur; Ritch, Robert
Glaucoma: Today and Tomorrow

Review Article

Translamina Cribrosa Pressure Difference as Potential Element in the Pathogenesis of Glaucomatous Optic Neuropathy Jonas, Jost B.; Wang, Ningli; Yang, Diya
Abstract: The main proven risk factor for glaucomatous optic neuropathy (GON) is an intraocular pressure (IOP) higher than the pressure sensibility of the optic nerve head allows. Fulfilling Koch postulates, numerous studies have shown that the presence of high IOP leads to GON, that lowering IOP stops the progression of GON, and that a re-increase in IOP again causes the progression of GON. There are, however, many patients with glaucoma who have statistically normal or low IOP, and despite low IOP values, they develop progressing GON. These observations led to findings that IOP is only 1 of 2 determinants of the translamina cribrosa pressure difference (TLCPD), which is the main pressure-related parameter for the physiology and pathophysiology of the optic nerve head. The second parameter influencing TLCPD is orbital cerebrospinal fluid pressure (CSFP) as the counter pressure against IOP across the lamina cribrosa. Recent experimental and clinical studies have suggested that a low CSFP could be associated with GON in normal-pressure glaucoma. These investigations included studies with an experimental long-term reduction in CSFP in monkeys, population-based studies, and clinical retrospective and prospective investigations on patients with normal-pressure glaucoma. Besides TLCPD, other ocular parameters influenced by CSFP may be choroidal thickness, retinal vein pressure and diameter, occurrence of retinal vein occlusions, and occurrence and severity of diabetic retinopathy.
Optical Coherence Tomography Imaging for Glaucoma – Today and Tomorrow Leung, Christopher Kai-Shun
Abstract: Digital imaging technologies for glaucoma diagnostics have evolved rapidly over the recent years. From time-domain optical coherence tomography (OCT) to spectral-domain and swept-source OCTs, the application of OCT for analysis of the anterior chamber angle and the optic nerve head (ONH) is expanding. The second-generation anterior segment swept-source OCT is able to image the configuration of the anterior chamber angle in 3 dimensions in less than 1 second and perform 360-degree analysis of the anterior chamber angle width for detection of angle closure. The morphology, density, and dimensions of the crystalline lens in relation to the anterior chamber can now be examined from the anterior corneal surface to the posterior lens surface, facilitating the investigation of the involvement of the crystalline lens in primary angle closure. Spectral-domain and swept-source OCTs have improved the measurement reliability of the lamina cribrosa and the neuroretinal rim configurations. Studying the deformation of the lamina cribrosa and ONH surfaces is relevant to decipher the mechanisms of ONH damage in the development and progression of glaucoma. Software and algorithms for automatic analysis of the anterior chamber angle dimensions and deformation of the ONH and lamina cribrosa surfaces are required to process large volumetric data sets, and they are under active development. It is expected that new imaging technologies will improve the detection and risk assessment of angle-closure and open-angle glaucomas.
Personalizing Intraocular Pressure: Target Intraocular Pressure in the Setting of 24-Hour Intraocular Pressure Monitoring Sit, Arthur J.; Pruet, Christopher M.
Abstract: Determining target intraocular pressure (IOP) in glaucoma patients is multifaceted, requiring attention to many different factors such as glaucoma type, severity of disease, age, race, family history, corneal thickness and hysteresis, and initial IOP. Even with all these variables accounted for, there are still patients who have progression of the disease despite achieving target IOP. Intraocular pressure variability has been identified as a potential independent risk factor for glaucoma progression but is currently difficult to quantify in individual patients. New technologies enabling measurement of both diurnal and nocturnal IOP may necessitate modifying our concept of target pressure.
Update on the Prevalence, Etiology, Diagnosis, and Monitoring of Normal-Tension Glaucoma Kim, Ko Eun; Park, Ki-Ho
Abstract: Glaucoma is a leading cause of blindness worldwide. Normal-tension glaucoma (NTG) is a type of open-angle glaucoma with intraocular pressure measurements always 21 mm Hg or less. A controversy surrounding NTG is the question of whether it should be regarded as a disease within the spectrum of primary open-angle glaucoma or as a distinctive disease entity. Nonetheless, NTG does have distinctive features compared with primary open-angle glaucoma: intraocular pressure–independent risk factors for development of NTG, characteristic patterns of structural and functional damage, and a unique disease course. This review provides an overview and update on the current issues surrounding the prevalence, etiology, diagnosis, and monitoring of NTG.
Glaucoma Suspect: Diagnosis and Management Chang, Robert T.; Singh, Kuldev
Abstract: Glaucoma suspect is a diagnosis reserved for individuals who do not definitively have glaucoma at the present time but have characteristics suggesting that they are at high risk of developing the disease in the future based on a variety of factors. This review provides a practical approach to individuals classified as glaucoma suspects caused by one or more of the following risk factors or indicators of disease: ocular hypertension, optic nerve features suggestive of glaucoma, visual field abnormalities, and other characteristics placing them at greater risk than the average population. In addition to diagnostic considerations, this overview provides information on therapeutic approaches to the glaucoma suspect.
Ocular Blood Flow and Influencing Factors for Glaucoma Nakazawa, Toru
Abstract: Open-angle glaucoma (OAG) is characterized by optic nerve fiber atrophy and deterioration of the visual field, corresponding to damage to the optic nerve head. Intraocular pressure (IOP) is currently the only evidence-based, treatable risk factor for OAG. However, normal-tension glaucoma, the most common type of OAG in Asia, is a type of glaucoma with an unclear pathogenesis. Glaucoma is suspected to be a multifactorial disease with IOP-dependent and IOP-independent risk factors, including decreased ocular blood flow (OBF), oxidative stress, decreased axoplasmic flow, and genetic background. A number of epidemiological studies have generated strong evidence that OBF may be an especially important risk factor for the progression of glaucoma. Recent innovations in laser speckle flowgraphy and optical coherence tomography–based angiography have allowed us to noninvasively monitor changes in the microcirculation of the optic nerve head with high reproducibility. Laser speckle flowgraphy–derived measurement parameters include mean blur rate and pulse wave form parameters, whereas the main optical coherence tomography angiography–derived parameter is the vessel index. Decreases in these parameters are associated with the severity of glaucomatous damage, and changes are detectible even in the earliest, preperimetric stage of glaucoma. In the future, OBF analysis may improve significantly because of continuing progress in the development of the relevant instruments. This review will summarize possible connections between systemic and OBF abnormalities and OAG, describe the scientific rationale for these connections, and discuss their potential implications. Thus, this review will summarize the role of OBF in glaucoma pathogenesis and discuss the wide range of IOP-independent risk factors.
Systemic Associations of Exfoliation Syndrome Ritch, Robert
Abstract: Exfoliation syndrome (XFS) is an age-related disease characterized by the production, deposition, and progressive accumulation of a white, fibrillar, extracellular material in many ocular tissues, most prominent on the anterior lens surface and pupillary border. Its prevalence increases steadily with age in all populations. It is the most common identifiable cause of open-angle glaucoma worldwide and is a potentially reversible or even curable disease. First described in Finland in 1917 by Lindberg, it has long been associated with open-angle glaucoma. However, in recent years, it is being increasingly reported in conjunction with a multiplicity of both ocular and systemic disorders, and the number of these is expected to grow, particularly with investigations based on attempts to associate other diseases with those genes known to be associated with XFS. Despite the focus on XFS as a cause of open-angle glaucoma for nearly a century, in reality it is still only an ocular manifestation of a protean systemic disease. It is a unique disorder with extensive and often serious ocular and systemic manifestations and not, as it has long been termed, a “form” or “type” of glaucoma. This misconception has delayed research into the molecular and cellular processes involved in its development, and the underestimation of its overall importance and its underlying causative mechanisms have largely been long ignored. The purpose of this article is to review the systemic disorders which are becoming increasingly associated with XFS. Reviews of epidemiology, genetics, biomarkers, molecular mechanisms of development, and ocular findings may be found elsewhere.
Update on the Medical Treatment of Primary Open-Angle Glaucoma Cheema, Anjum; Chang, Robert T.; Shrivastava, Anurag; Singh, Kuldev
Abstract: Glaucoma comprises a group of progressive, neurodegenerative disorders characterized by retinal ganglion cell death and nerve fiber layer atrophy. Several randomized controlled trials have consistently demonstrated the efficacy of intraocular pressure lowering to slow or halt the measurable progression of the disease. Medical therapy, in places where it is easily accessible, is often the primary method to lower intraocular pressure. We review the medical options currently available and possible future options currently in development. The 5 contemporary classes of topical agents in use include prostaglandin analogs, beta blockers, carbonic anhydrase inhibitors, alpha agonists, and cholinergics. In addition, several fixed combination agents are commercially available. Agents from each of these classes have unique mechanisms of action, adverse effects, and other characteristics that impact how they are used in clinical practice. Despite the plethora of medical options available, there are limitations to topical ophthalmic therapy such as the high rate of noncompliance and local and systemic adverse effects. Alternate and sustained drug delivery models, such as injectable agents and punctal plug delivery systems, may in the future alleviate some such concerns and lead to increased efficacy of treatment while minimizing adverse effects.
Management of Primary Angle-Closure Glaucoma Lai, Jimmy; Choy, Bonnie N. K.; Shum, Jennifer W. H.
Abstract: Primary angle-closure glaucoma (PACG) is a progressive optic nerve degeneration and is defined as a glaucomatous optic neuropathy with associated characteristic enlargement of optic disc cupping and visual field loss that is secondary to ocular hypertension caused by closure of the drainage angle. Angle closure is caused by appositional approximation or adhesion between the iris and the trabecular meshwork. The main treatment strategy for PACG lies in the reduction of intraocular pressure, reopening of the closed angle, and possible prevention of further angle closure. There is no universally agreed best surgical treatment for PACG. Trabeculectomy, goniosynechialysis (GSL), glaucoma implant, and cyclodestructive procedures are effective surgical options. Each of them plays an important role in the management of PACG with its own pros and cons. Accumulating evidence is available to show the effectiveness of visually significant and visually nonsignificant cataract extraction in the treatment of PACG. Trabeculectomy and GSL are often combined with cataract extraction, which may offer additional pressure control benefits to patients with PACG. This review article will discuss laser peripheral iridotomy, argon laser peripheral iridoplasty, and surgeries such as GSL, phacoemulsification, and phaco plus glaucoma surgeries that lower intraocular pressure and also alter the anterior segment and/or drainage angle anatomy. Currently, glaucoma implants and cyclodestruction are mainly reserved for PACG patients who have failed previous filtering operations. Their role as initial surgical treatment for PACG will not be discussed.
Selective Laser Trabeculoplasty: An Update Kennedy, Jeffrey B.; SooHoo, Jeffrey R.; Kahook, Malik Y.; Seibold, Leonard K.
Abstract: Selective laser trabeculoplasty (SLT) is an effective treatment option for the reduction of intraocular pressure (IOP) in patients with ocular hypertension or open-angle glaucoma. The mechanism by which SLT lowers IOP is not completely understood and is likely multifactorial. Published studies indicate that SLT is at least as effective as argon laser trabeculoplasty or medications at lowering IOP in many forms of glaucoma. In addition to IOP reduction, SLT may decrease IOP fluctuation and can be successfully used as primary or adjunctive therapy for the management of both early and advanced glaucoma. However, SLT may not be effective in certain forms of glaucoma, and the IOP-lowering effect seems to wane with time. High pretreatment IOP is the strongest predictor of treatment success, even in patients with normal-tension glaucoma. Repeatability of SLT has been controversial, but recent evidence suggests that it can be successfully repeated to achieve additional or recurrent IOP reduction, even in eyes that only had a modest response to initial treatment. Adverse events are uncommon after SLT, and the most common complications such as discomfort and inflammation are typically mild and transient. Further investigation is required to determine the optimal treatment parameters for SLT treatment. Limited evidence suggests that SLT is cost-effective as primary therapy for patients with glaucoma.
Nanotechnology Applications for Glaucoma Cetinel, Sibel; Montemagno, Carlo
Abstract: Glaucoma is the second leading cause of blindness worldwide, and the antiglaucoma treatments currently available suffer from various complications. Nanotechnology-based treatments show a great deal of promise in overcoming these complications and form the basis for next-generation glaucoma treatment strategies, with the help of applications such as controlled release, targeted delivery, increased bioavailability, diffusion limitations, and biocompatibility. Significant progress has been made in nanomedicine in the efficiency of antiglaucoma medications, nanofabrication systems such as microelectromechanical systems that remove the limitations of nanodevices, and tissue regeneration vesicles for developing glaucoma treatments not based on intraocular pressure. With the use of these advanced technologies, the prevention of glaucoma-induced blindness will be possible in the near future. Herein, we reviewed the recent advances in nanotechnology-based treatment strategies for glaucoma.
Lowering of Intraocular Pressure After Phacoemulsification in Primary Open-Angle and Angle-Closure Glaucoma: A Bayesian Analysis Thomas, Ravi; Walland, Mark; Thomas, Aleysha; Mengersen, Kerrie
Abstract: Phacoemulsification as treatment for primary open-angle glaucoma (POAG) remains more controversial than for primary angle-closure glaucoma (PACG). If the objective of glaucoma surgery is an additional greater than or equal to 5 to 6 mm Hg reduction of intraocular pressure (IOP), the role of phacoemulsification should be based on the probability of achieving this. A Bayesian analysis of available data was performed to calculate the change in IOP after phacoemulsification in POAG and PACG. Standard meta-analysis formulation with prephacoemulsification and postphacoemulsification IOP—assumed to have normal distributions, with study-specific means and SDs—was used. Absolute and relative change in IOP was calculated using different priors, and sensitivity analyses were performed. The prior that just included a decrease of greater than or equal to 6 mm Hg in the 95% credible interval was identified. The probability of achieving greater than or equal to 5 to 6 mm Hg decrease in IOP (and other levels) was calculated. Depending on the prior, the probability of achieving a greater than or equal to 5 mm Hg reduction in IOP in POAG varied from 0.1% to 3%. Confidence in a greater than or equal to 6 mm Hg decrease required a prior belief that phacoemulsification produces a mean decrease of 7 mm Hg. The probability of a decrease in IOP was greater in PACG: approximately 50% probability of a greater than or equal to 5 mm Hg decrease in PACG uncontrolled on medications. Phacoemulsification in POAG has a high probability of producing a small decrease in IOP that may be useful in early, well-controlled disease. The probability of a clinically significant decrease of greater than or equal to 5 to 6 mm Hg—required for advanced/uncontrolled disease—is low. Results support the role of phacoemulsification in PACG.
Updates on the Surgical Management of Pediatric Glaucoma Tan, Yar-Li; Chua, Jocelyn; Ho, Ching-Lin
Abstract: Childhood glaucoma is known to be one of the most challenging conditions to manage. Surgical management is more complicated than in adults because of differences in anatomy from adults along with variations in anatomy caused by congenital and developmental anomalies, wide-ranging pathogenetic mechanisms, a more aggressive healing response, and a less predictable postoperative course. Challenges in postoperative examination and management in less cooperative children and the longer life expectancies preempting the need for future surgeries and reinterventions are also contributing factors. Angle surgery is usually the first-line treatment in the surgical management of primary congenital glaucoma because it has a relatively good success rate with a low complication rate. After failed angle surgery or in cases of secondary pediatric glaucoma, options such as trabeculectomy, glaucoma drainage devices, or cyclodestructive procedures can be considered, depending on several factors such as the type of glaucoma, age of the patient, and the severity and prognosis of the disease. Various combinations of these techniques have also been studied, in particular combined trabeculotomy-trabeculectomy, which has been shown to be successful in patients with moderate-to-advanced disease. Newer nonpenetrating techniques, such as viscocanalostomy and deep sclerectomy, have been reported in some studies with variable results. Further studies are needed to evaluate these newer surgical techniques, including the use of modern minimally invasive glaucoma surgeries, in this special and diverse group of young patients.
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