As each mm Hg of IOP reduction reduces the risk of glaucomatous development or further glaucoma progression, with associated further functional vision loss,^1,2,3,4 what prescribing principles should we apply if we decide to start topical treatment?

Here’s a minimalist perspective to help meet our goals of preserving functional vision among our glaucoma patients, while still meeting their expectations of sufficient IOP control.⁵

Maximum tolerated medical therapy (MTMT)
We cannot talk about treatment and, specifically, topical medical therapy, without first recognizing (and continually re-evaluating) target IOP ranges — that target IOP range that prevents “…further progression of glaucomatous visual field (VF) loss, without compromising a patient's quality of life (Qol).”⁶ While this target IOP “…is at best an educated guess,”⁷ “…it is reasonable to infer that a specific threshold exists for an individual eye below which the risk of IOP-induced optic nerve injury is minimal.”⁸ Accordingly, and as shown in the below sidebar, it is recommended to establish a target IOP range (for each eye separately) and continually re-evaluate this range (for each eye separately) at every visit based on specific factors unique to the patient and if “…the VF is worsening at a rate that may threaten QoL during the patient’s expected lifetime, then the target IOP should be lowered further and treatment changed.”⁹ 

Once the target IOP range has been established, and topical medical therapy is selected, then such treatment usually begins with prostaglandin analogues, then carbonic anhydrase inhibitors or beta blockers, then alpha agonists,⁷ with a stepwise approach. Challenging this traditional step therapy head on, interim results from an ongoing study found that a “larger proportion of patients will reach their target IOP more rapidly with initial intensive treatment (multiple classes of medications plus selective laser trabeculoplasty [SLT]) than with conventional step treatment.^10,11” In recognizing that both approaches potentially have various therapeutic combinations¹² with various levels of tolerability, MTMT usually (and ultimately) has minimal additive benefits with each agent likely adding less beneficial effect than the previous.^7,13 Adding to these “diminishing returns”⁷ is the proportionate decrease in patient adherence — “the wild card in the deck for controlling glaucoma progression”¹⁴ and increasing proportionate ocular surface disease.¹⁵ Based on these, and among other factors, Fecthner proposed years ago that the  “concept of MTMT must be retired…The era of MTMT is past.”¹³ 

Minimally Invasive Medical Therapy (MIMT)
Beyond MTMT, Fecthner recommended “optimal medical therapy,” “where the practitioner uses the least amount of medicine to achieve the desired goal with the least adverse effect.”¹³ In my mind, this principle may be evolved and elevated further to what I call minimally invasive medical therapy, or MIMT. This is the point where we supplement medical therapy with treatments (SLT, intracameral implants, and/or MIGS), which may be more effective and more sustainable over the long course of the disease. In short, and in addition to our goal of preserving vision and Qol, our goal is to use the least amount of medication (and consequent inconvenience, costs, and side effects) to achieve the therapeutic response needed.

The minimalist approach
We may know when we are at MTMT, when we need to use a drop instruction sheet to write for the patient all the prescribed drops and when to take them. Conversely, we know that we are at MIMT when we are less likely (if at all) to supply the patient with a drop instruction sheet. To that point, intentionally look for “advantageous subtractive changes.”¹⁶ OM 
“When things aren’t adding up in your life, start subtracting.” - Author unknown

References

1. Kass MA, Heuer DK, Higginbotham EJ, et al. The Ocular Hypertension Treatment Study: a randomized trial determines that topical ocular hypotensive medication delays or prevents the onset of primary open-angle glaucoma. Arch Ophthalmol. 2002;120(6):701–830. doi: 10.1001/archopht.120.6.701.
2. Heijl A, Leske MC, Bengtsson B, et al. Reduction of intraocular pressure and glaucoma progression: results from the Early Manifest Glaucoma Trial. Arch Ophthalmol. 2002;120(10):1268–1279. doi: 10.1001/archopht.120.10.1268.
3. Musch DC, Gillespie BW, Niziol LM, Lichter PR, Varma R; CIGTS Study Group. Intraocular pressure control and long-term visual field loss in the Collaborative Initial Glaucoma Treatment Study. Ophthalmology. 2011;118(9):1766–1773. doi: 10.1016/j.ophtha.2011.01.047.
4. The Advanced Glaucoma Intervention Study (AGIS): 7. The relationship between control of intraocular pressure and visual field deterioration. The AGIS Investigators. Am J Ophthalmol. 2000;130(4):429–440. doi: 10.1016/s0002-9394(00)00538-9.
5. Safitri A, Konstantakopoulou E, Hu K, Gazzard G. Treatment expectations in glaucoma: what matters most to patients? Eye (Lond). 2023;37(16):3446-3454. doi: 10.1038/s41433-023-02532-w.
6. Sihota R, Angmo D, Ramaswamy D, Dada T. Simplifying "target" intraocular pressure for different stages of primary open-angle glaucoma and primary angle-closure glaucoma. Indian J Ophthalmol. 2018;66(4):495-505. doi: 10.4103/ijo.IJO_1130_17. 
7. Singh K, Shrivastava A. Medical management of glaucoma: principles and practice. Indian J Ophthalmol. 2011;59 Suppl(Suppl1):S88-S92. doi: 10.4103/0301-4738.73691.
8. Jayaram H. Intraocular pressure reduction in glaucoma: Does every mmHg count? Taiwan J Ophthalmol. 2020;10(4):255-258. doi: 10.4103/tjo.tjo_63_20.
9. European Glaucoma Society Terminology and Guidelines for Glaucoma, 5th Edition. Br J Ophthalmol. 2021;105(Suppl 1):1-169. doi: 10.1136/bjophthalmol-2021-egsguidelines. 
10. Bengtsson B, Lindén C, Heijl A, Andersson-Geimer S, Aspberg J, Jóhannesson G. The glaucoma intensive treatment study: interim results from an ongoing longitudinal randomized clinical trial. Acta Ophthalmol. 2022;100(2):e455-e462. doi: 10.1111/aos.14978. 
11. Lindén C, Heijl A, Jóhannesson G, Aspberg J, Andersson Geimer S, Bengtsson B. Initial intraocular pressure reduction by mono- versus multi-therapy in patients with open-angle glaucoma: results from the Glaucoma Intensive Treatment Study. Acta Ophthalmol. 2018;96(6):567-572 doi: 10.1111/aos.13790. 
12. Realini T, Fechtner RD. 56,000 ways to treat glaucoma. Ophthalmology. 2002;109(11):1955-6. doi: 10.1016/s0161-6420(02)01437-9.
13. Fechtner RD, Singh K. Maximal glaucoma therapy. J Glaucoma. 2001;10(5 Suppl 1):S73-5. doi: 10.1097/00061198-200110001-00026. 
14. Fingeret M, Dickerson JE Jr. The Role of Minimally Invasive Glaucoma Surgery Devices in the Management of Glaucoma [published correction appears in Optom Vis Sci. 2018;95(6):554]. doi: 10.1097/OPX.0000000000001173.
15. Asiedu K, Abu SL. The impact of topical intraocular pressure lowering medications on the ocular surface of glaucoma patients: A review. J Curr Ophthalmol. 2018;31(1):8-15. doi: 10.1016/j.joco.2018.07.003.
16. Adams GS, Converse BA, Hales AH, Klotz LE. People systematically overlook subtractive changes. Nature. 2021;592(7853):258-261. doi: 10.1038/s41586-021-03380-y.

AUSTIN LIFFERTH, OD, FAAO is clinical editor of Optometric Management. He practices at Center for Sight, is a member of the Optometric Glaucoma Society, and a Glaucoma Diplomate of the American Academy of Optometry. For additional glaucoma cases, you can also follow Dr. Lifferth on his Instagram account: glaucomaqd. Email him at glaucomaqd@yahoo.com.