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Achievements and Limits of Current Medical Therapy of Glaucoma

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Achievements and Limits of Current Medical Therapy of Glaucoma Bettin P, Khaw PT (eds): Glaucoma Surgery. 2nd, revised and extended edition. Dev Ophthalmol. Basel, Karger, 2017, vol 59, pp 1–14 ( DOI: 10.1159/000458482 ) Achievements and Limits of Current Medical Therapy of Glaucoma Pelagia Kalouda · Christina Keskini · Eleftherios Anastasopoulos · Fotis Topouzis Laboratory of Research and Clinical Applications in Ophthalmology, Aristotle University of Thessaloniki, AHEPA Hospital, Thessaloniki , Greece Abstract ery systems are being investigated to open new horizons Prescribing medical therapy for the treatment of glauco- in glaucoma management. Although the general rule is ma can be a complex process since many parameters to initiate glaucoma management with medical treat- should be taken into consideration regarding its achieve- ment, the limits of medical therapy should be considered ments and limits. Today, a variety of options, including to identify those patients in need of surgical manage- multiple drug classes and multiple agents within classes, ment. © 2017 S. Karger AG, Basel are available to the clinician, but caution should be given to their side effects and contraindications. Glaucoma pa- tients with preexisting ocular surface disease should be State of the Art treated with caution, and preferably with preservative- free formulations, as there is an increased risk for symp- Glaucoma is a medical term describing a group of tom deterioration. The development and use of progressive optic neuropathies characterized by fixed-combination therapies has reduced the preserva- the degeneration of retinal ganglion cells and of tive-related side effects that threaten patient adherence the retinal nerve fiber layer, resulting in changes and has minimized the washout effect of multiple instil- in the optic nerve head. Glaucoma is one of the lations. Adherence to medical treatment is not only cru- leading causes of blindness worldwide and pres- cial to its efficacy but also to its cost-effectiveness. Further ents with a significant prevalence in the popula- factors to consider are that there are patients who are tion. nonresponders to treatment, and also that the target in- It is therefore essential to accurately define and traocular pressure (IOP) cannot be reached in all patients, detect the population that should be treated for regardless of the response to treatment. The progression glaucoma and to precisely define the goal of our of damage can occur even under maximum medical intervention. In order to decide who should be treatment or maximally tolerated medical treatment, and treated for glaucoma, it has to be considered that regardless of whether low IOP levels are reached. Further- the rate of ganglion cell loss and resulting func- more, there is some conflict between medical treatment tional decay is very different among different and quality of life due to long-term everyday use and to glaucoma eyes. An older patient, diagnosed late side effects of treatment. New molecules and new deliv- in life, with a moderate rate of progression has a Downloaded by: Massachusetts Eye & Ear 205.166.145.254 - 2/20/2018 5:26:46 PM much lower risk of developing severe functional 5] . Moreover, OHTS [2] revealed the following impairment than a younger patient with the same data for the progression of OH to primary open- amount of field loss at diagnosis and rate of pro- angle glaucoma: (a) a 22% increased risk per de- gression. Moreover, a very slow rate of progres- cade of age, (b) a 10% increased risk per 1-mmHg sion may be tolerated by a patient, while a rapid increase in IOP, and (c) a 71% increased risk per rate of progression requires a considerably lower 40-μm decrease in central corneal thickness. target pressure. The goal of glaucoma treatment is to maintain Target Intraocular Pressure the patient’s visual function and related quality of Target IOP is a useful concept in glaucoma man- life, at a sustainable cost. Regarding the cost of agement. It can be described as the upper limit of treatment, factors like inconvenience, side effects, IOP that is estimated to prevent further glauco- and financial implications for the individual and matous damage or that can slow disease progres- society require careful evaluation [1] . According sion to a minimum [1] . Target IOP will vary for to the EGS guidelines, patients for whom treat- each patient depending on the IOP level before ment for glaucoma should be considered are treatment, stage of glaucoma, rate of progression those with diagnosed or suspected glaucoma who during follow-up, age and life expectancy, and the are: (a) at risk of developing functional impair- presence of other risk factors, such as exfoliation ment that will lead to a deterioration in visual syndrome. The target pressure should be reas- function-related quality of life, (b) patients with a sessed and modified regularly depending on the definitive glaucomatous visual field (VF), partic- patient’s course of the disease. ularly those with progressive disease, and (c) pa- tients with significant changes in the optic nerve Progression of Visual Field Damage head and retinal nerve fiber layer characteristic of The functional impact of glaucoma is mainly as- glaucoma. In the decision to treat glaucoma or sessed by evaluation of the VF damage. The de- not there are additional factors to consider, which tection of VF damage progression directly affects are mentioned below. the therapeutic decisions and the patients’ quality of life. Different analytical tools have been devel- Risk Assessment in Glaucoma oped in order to identify VF progression. Com- Risk factors for the progression from ocular hy- puter-assisted progression can be divided into pertension (OH) to glaucoma are: intraocular event- and trend-based analyses. pressure (IOP), age, central corneal thickness, Event-based analyses answer the question of vertical cup/disk ratio, and standard deviation whether there is disease progression or not by pattern in the VF [2, 3] . Current risk calculators comparing each follow-up examination with the that estimate an ocular hypertensive patient’s risk baseline. Using Glaucoma Change Probability of developing glaucoma over a 5-year period of (GCP) software, all VF tests are compared to time include the aforementioned parameters and baseline consisting of an average of 2 baseline should be used for populations that resemble the tests. However, this analysis is based on the total population studied in the Ocular Hypertension deviation plot, which means that it may be affect- Treatment Study (OHTS) [2] and the European ed by diffuse media opacities. On the other hand, Glaucoma Prevention Study (EGPS) [3] . Guided Progression Analysis (GPA) software is Additional risk factors that may increase the based on the pattern deviation plot, meaning it risk of glaucoma and should be considered in the evaluates progression adjusted for diffuse defects. risk assessment are exfoliation, cardiovascular Trend-based analyses are primarily designed disease, a positive family history, and myopia [4, to determine the rate of progression and show the 2 Kalouda · Keskini · Anastasopoulos · Topouzis Bettin P, Khaw PT (eds): Glaucoma Surgery. 2nd, revised and extended edition. Dev Ophthalmol. Basel, Karger, 2017, vol 59, pp 1–14 ( DOI: 10.1159/000458482 ) Downloaded by: Massachusetts Eye & Ear 205.166.145.254 - 2/20/2018 5:26:46 PM overall progression of VF defects. Trend-based considered as the most suitable initial and follow- progression displays the linear regression analysis up treatment for open-angle glaucoma, as well as of the VF index. They help the practitioner to as- for many types of chronic angle-closure glauco- sess the risk of future visual disability associated ma. There are many classes of antiglaucoma drugs with that rate of progression and the current stage that act either on the reduction of aqueous humor of damage. production or on the enhancement of the aque- ous humor outflow facility, or on both. Principles of Economic Evaluation/Cost Effectiveness First-Line Drugs Glaucoma is a chronic disease that requires life- Prostaglandin Analogues long management. Extensive and often continu- Antiglaucoma drugs were first introduced in ing therapeutic interventions are required due to glaucoma therapy in 1875, but it was in the 1990s the chronic nature of the disease. The costs (direct that prostaglandin derivatives (latanoprost ini- and indirect) and effects (short and long term) of tially and then travoprost, bimatoprost, and taflu- alternative courses of action, such as medical prost) were available for glaucoma treatment and therapies and surgery, need to be compared in or- gradually replaced β-blockers as first-line thera- der to determine cost-effective treatments for py. Their widespread adoption is due to the fact glaucoma. The direct costs are associated with di- that their IOP-lowering effect is superior to any agnosis, treatment, and monitoring, whereas the other single antiglaucoma drug, their side effects indirect costs are associated with progressive dis- appear to be very mild, and they require just once- ease and visual impairment. Moreover, short- daily administration. term effects are related to diagnosis, adverse ef- Their main mode of action is to enhance the fects, and recovery from therapies, while long- uveoscleral outflow (nonconventional pathway), term effects are related to visual outcome. reducing IOP by 25–35%. They degrade collagen It has been suggested that conventional medi- by activating a cascade which includes tissue-re- cation may be more cost-effective than one-off modeling enzymes and transcription factors. This surgery in the short term, but in the long term a leads to the opening of the intercellular spaces for successful surgery is more cost-effective because fluid drainage, which causes increased uveo- the on-going cost of medications is avoided [6] . scleral flow rates and hence decreases IOP. A re- Reported costs of glaucoma therapy vary, but ran- duction in IOP starts approximately 2–4 hours domized controlled treatment trials rarely include after topical administration. The therapeutic ef- a cost-effectiveness analysis.
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