Alternatives to Topical Glaucoma Medication for Glaucoma Management

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Abstract

Topical glaucoma medications have favorable safety and efficacy, but their use is limited by factors such as side effects, nonadherence, costs, ocular surface disease, intraocular pressure fluctuations, diminished quality of life, and the inherent difficulty of penetrating the corneal surface. Although traditionally these limitations have been accepted as an inevitable part of glaucoma treatment, a rapidly-evolving arena of minimally invasive surgical and laser interventions has initiated the beginnings of a reevaluation of the glaucoma treatment paradigm. This reevaluation encompasses an overall shift away from the reactive, topical-medication-first default and a shift toward earlier intervention with laser or surgical therapies such as selective laser trabeculoplasty, sustained-release drug delivery, and micro-invasive glaucoma surgery. Aside from favorable safety, these interventions may have clinically important attributes such as consistent IOP control, cost-effectiveness, independence from patient adherence, prevention of disease progression, and improved quality of life.

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Reduction of intraocular pressure and glaucoma progression: results from the Early Manifest Glaucoma Trial.

Anders Heijl, M. Leske, Bo Bengtsson … (2002)

To provide the results of the Early Manifest Glaucoma Trial, which compared the effect of immediately lowering the intraocular pressure (IOP), vs no treatment or later treatment, on the progression of newly detected open-angle glaucoma. Randomized clinical trial. Two hundred fifty-five patients aged 50 to 80 years (median, 68 years) with early glaucoma, visual field defects (median mean deviation, -4 dB), and a median IOP of 20 mm Hg, mainly identified through a population screening. Patients with an IOP greater than 30 mm Hg or advanced visual field loss were ineligible. Patients were randomized to either laser trabeculoplasty plus topical betaxolol hydrochloride (n = 129) or no initial treatment (n = 126). Study visits included Humphrey Full Threshold 30-2 visual field tests and tonometry every 3 months, and optic disc photography every 6 months. Decisions regarding treatment were made jointly with the patient when progression occurred and thereafter. Glaucoma progression was defined by specific visual field and optic disc outcomes. Criteria for perimetric progression were computer based and defined as the same 3 or more test point locations showing significant deterioration from baseline in glaucoma change probability maps from 3 consecutive tests. Optic disc progression was determined by masked graders using flicker chronoscopy plus side-by-side photogradings. After a median follow-up period of 6 years (range, 51-102 months), retention was excellent, with only 6 patients lost to follow-up for reasons other than death. On average, treatment reduced the IOP by 5.1 mm Hg or 25%, a reduction maintained throughout follow-up. Progression was less frequent in the treatment group (58/129; 45%) than in controls (78/126; 62%) (P =.007) and occurred significantly later in treated patients. Treatment effects were also evident when stratifying patients by median IOP, mean deviation, and age as well as exfoliation status. Although patients reported few systemic or ocular conditions, increases in clinical nuclear lens opacity gradings were associated with treatment (P =.002). The Early Manifest Glaucoma Trial is the first adequately powered randomized trial with an untreated control arm to evaluate the effects of IOP reduction in patients with open-angle glaucoma who have elevated and normal IOP. Its intent-to-treat analysis showed considerable beneficial effects of treatment that significantly delayed progression. Whereas progression varied across patient categories, treatment effects were present in both older and younger patients, high- and normal-tension glaucoma, and eyes with less and greater visual field loss.

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Preservatives in eyedrops: the good, the bad and the ugly.

Christophe Baudouin, Antoine Labbe, Hong Liang … (2010)

There is a large body of evidence from experimental and clinical studies showing that the long-term use of topical drugs may induce ocular surface changes, causing ocular discomfort, tear film instability, conjunctival inflammation, subconjunctival fibrosis, epithelial apoptosis, corneal surface impairment, and the potential risk of failure for further glaucoma surgery. Subclinical inflammation has also been described in patients receiving antiglaucoma treatments for long periods of time. However, the mechanisms involved, i.e., allergic, toxic, or inflammatory, as well as the respective roles of the active compound and the preservative in inducing the toxic and/or proinflammatory effects of ophthalmic solutions, is still being debated. The most frequently used preservative, benzalkonium chloride (BAK), has consistently demonstrated its toxic effects in laboratory, experimental, and clinical studies. As a quaternary ammonium, this compound has been shown to cause tear film instability, loss of goblet cells, conjunctival squamous metaplasia and apoptosis, disruption of the corneal epithelium barrier, and damage to deeper ocular tissues. The mechanisms causing these effects have not been fully elucidated, although the involvement of immunoinflammatory reactions with the release of proinflammatory cytokines, apoptosis, oxidative stress, as well as direct interactions with the lipid components of the tear film and cell membranes have been well established. Preservative-induced adverse effects are therefore far from being restricted to only allergic reactions, and side effects are often very difficult to identify because they mostly occur in a delayed or poorly specific manner. Care should therefore be taken to avoid the long-term use of preservatives, otherwise a less toxic alternative to BAK should be developed, as this weakly allergenic but highly toxic compound exerts dose- and time-dependent effects. On the basis of all these experimental and clinical reports, it would be advisable to use benzalkonium-free solutions whenever possible, especially in patients with the greatest exposure to high doses or prolonged treatments, in those suffering from preexisting or concomitant ocular surface diseases, and those experiencing side effects related to the ocular surface. Indeed, mild symptoms should not be underestimated, neglected, or denied, because they may very well be the apparent manifestations of more severe, potentially threatening subclinical reactions that may later cause major concerns. Copyright (c) 2010 Elsevier Ltd. All rights reserved.

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The Ocular Hypertension Treatment Study: a randomized trial determines that topical ocular hypotensive medication delays or prevents the onset of primary open-angle glaucoma.

Richard Miller, D Heuer, Janet Parrish … (2002)

Primary open-angle glaucoma (POAG) is one of the leading causes of blindness in the United States and worldwide. Three to 6 million people in the United States are at increased risk for developing POAG because of elevated intraocular pressure (IOP), or ocular hypertension. There is no consensus on the efficacy of medical treatment in delaying or preventing the onset of POAG in individuals with elevated IOP. Therefore, we designed a randomized clinical trial, the Ocular Hypertension Treatment Study. To determine the safety and efficacy of topical ocular hypotensive medication in delaying or preventing the onset of POAG. A total of 1636 participants with no evidence of glaucomatous damage, aged 40 to 80 years, and with an IOP between 24 mm Hg and 32 mm Hg in one eye and between 21 mm Hg and 32 mm Hg in the other eye were randomized to either observation or treatment with commercially available topical ocular hypotensive medication. The goal in the medication group was to reduce the IOP by 20% or more and to reach an IOP of 24 mm Hg or less. The primary outcome was the development of reproducible visual field abnormality or reproducible optic disc deterioration attributed to POAG. Abnormalities were determined by masked certified readers at the reading centers, and attribution to POAG was decided by the masked Endpoint Committee. During the course of the study, the mean +/- SD reduction in IOP in the medication group was 22.5% +/- 9.9%. The IOP declined by 4.0% +/- 11.6% in the observation group. At 60 months, the cumulative probability of developing POAG was 4.4% in the medication group and 9.5% in the observation group (hazard ratio, 0.40; 95% confidence interval, 0.27-0.59; P<.0001). There was little evidence of increased systemic or ocular risk associated with ocular hypotensive medication. Topical ocular hypotensive medication was effective in delaying or preventing the onset of POAG in individuals with elevated IOP. Although this does not imply that all patients with borderline or elevated IOP should receive medication, clinicians should consider initiating treatment for individuals with ocular hypertension who are at moderate or high risk for developing POAG.

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Author and article information

Journal

Journal ID (nlm-ta): Clin Ophthalmol

Journal ID (iso-abbrev): Clin Ophthalmol

Journal ID (publisher-id): opth

Title: Clinical Ophthalmology (Auckland, N.Z.)

Publisher: Dove

ISSN (Print): 1177-5467

ISSN (Electronic): 1177-5483

Publication date (Electronic): 14 December 2023

Publication date Collection: 2023

Volume: 17

Pages: 3899-3913

Affiliations

[1 ]Advanced Vision Care , Los Angeles, CA, USA

[2 ]Vance Thompson Vision , Sioux Falls, SD, USA

[3 ]John A. Moran Eye Center, University of Utah , Salt Lake City, UT, USA

[4 ]Department of Ophthalmology and Visual Sciences, Washington University in St. Louis School of Medicine , St. Louis, MO, USA

[5 ]Eye Centers of Racine and Kenosha , Kenosha, WI, USA

Author notes

Correspondence: Sahar Bedrood, Advanced Vision Care , 2080 Century Park East Suite 911, Los Angeles, CA, 90067, USA, Tel +1 (310) 229-1220, Email saharbedrood@gmail.com

Article

Publisher ID: 439457

DOI: 10.2147/OPTH.S439457

PMC ID: 10726774

PubMed ID: 38111854

SO-VID: 07469280-d200-47b6-96a3-2bdc6c62d35f

License:

This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License ( http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms ( https://www.dovepress.com/terms.php).

History

Date received : 09 September 2023

Date accepted : 22 November 2023

Page count

Figures: 0, References: 159, Pages: 15

Funding

Funded by: Glaukos Corporation;

No funding was provided for the creation of this manuscript. Publication fees were provided by Glaukos Corporation.

Alternatives to Topical Glaucoma Medication for Glaucoma Management

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Karger: Ophthalmology

Most cited references 156

Reduction of intraocular pressure and glaucoma progression: results from the Early Manifest Glaucoma Trial.

Preservatives in eyedrops: the good, the bad and the ugly.

The Ocular Hypertension Treatment Study: a randomized trial determines that topical ocular hypotensive medication delays or prevents the onset of primary open-angle glaucoma.

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