News & Position Statements

The United States Supreme Court’s decision to end race-conscious admissions policies at colleges and universities, and the subsequent complaints filed following the Court’s ruling,  has led us ALL to question where we stand as organizations, institutions, and leaders.  The American Glaucoma Society reaffirms its commitment to support and advocate for our diverse patients, trainees, colleagues, and communities.  We will continue to support programs and research that will help to eliminate racial and gender disparities in glaucoma care and research.  The American Glaucoma Society upholds that diversity of thought, experience, identity, and life journeys are critical to excellence in patient care, research, and education. We continue to aspire to build a diverse and inclusive community of glaucoma clinicians, educators, and researchers.

 2022

Unifying testing standards could reduce patient burden and costs from redundant testing and make old test results easier to integrate into algorithms moving forward.

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 2022

Unnecessary waste of perioperative topical ophthalmic medications (eyedrops and eye ointments) significantly increases the cost and carbon footprint of ophthalmic surgery as well as the risk of periodic drug shortages. This document, endorsed by the American Society of Cataract and Refractive Surgery (ASCRS), the American Academy of Ophthalmology (AAO), the American Glaucoma Society (AGS), and the Outpatient Ophthalmic Surgery Society (OOSS), establishes recommendations to reduce costly and unnecessary waste of topical medication.

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 2022

Unmet Needs in the Detection, Diagnosis, Monitoring, Treatment, and
Understanding of Primary Open-Angle Glaucoma: A Position Statement of the
American Glaucoma Society and the American Society of Cataract and
Refractive Surgery

J. Crawford Downs, PhD - Birmingham, Alabama
David Fleischman, MD, MS - Chapel Hill, North Carolina
on behalf of the 2020e2022 Research Committee of the American Glaucoma Society and the
2020e2022 Glaucoma Clinical Committee of the American Society of Cataract and Refractive
Surgery

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 2022

In an effort to better serve the needs of our patients, the American Glaucoma Society (AGS) calls on our commercial partners to improve electronic data standardization. Better data interoperability will improve patient safety and care by ensuring all clinical information is associated with the correct patient and can be easily integrated with data from multiple locations to better allow true disease monitoring over time. The COVID-19 pandemic has hastened a transition to non-traditional care models such as hybrid visits and home disease monitoring that will depend on adoption of these standards. Likewise, growing research interests in areas such as big data and artificial intelligence rely on accurate and fluid data integration to meet their potential. Below we make the case for working with our vendors to achieve widespread adoption of both existing and new standards to improve the care we provide.

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 2021

Glaucoma is a common ophthalmic disorder characterized by typical optic nerve damage and vision loss. It is most commonly associated with elevated or dysregulated intraocular pressure (IOP), although there is evidence that other factors contribute to the disease. Glaucoma is a leading cause of irreversible blindness worldwide. Its prevalence in the United States is approximately 1,900 per 100,000 persons over age forty, and the condition is responsible for upwards of 9 million clinic visits each year.1-3 In the United States, where annual spending on optic nerve disorders is estimated at $5.8 billion annually,4 glaucoma is a significant public health concern. The American Glaucoma Society (AGS) and the American Society of Cataract and Refractive Surgery (ASCRS) are committed to bringing greater attention to the current challenges that exist in the detection, diagnosis, monitoring, treatment and understanding of open-angle glaucoma.

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Glaucoma is mostly associated with an older population; however, it does occur in women of childbearing potential. In a survey of UK consultant ophthalmologists, more than one-quarter of respondents reported on having to deal with glaucoma management in the pregnant patient, and 31% of these were unsure about how they would deal with the situation. 1 This highlights that glaucoma in the pregnant patient is an issue of significant prevalence and that guidelines to assist with delivery of care are needed. There are multiple challenges and uncertainties related to the management of women planning a pregnancy, during pregnancy, and during the breastfeeding period. The approach to treatment must consider the risks of treatment to both the mother and the fetus versus the risk of vision loss for the mother. It is important to have a coordinated team approach when caring for the pregnant patient with glaucoma, and the family physician, obstetrician and other healthcare providers ideally should be included in the decision-making process. This review is meant to present a practical approach to managing the pregnant and breastfeeding patient with glaucoma and to serve as a quick reference guide facilitating simple clinical application.

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Endorsed by AGS Board of Directors – October 2019

May 7, 2021

AGS, AAO, and ASCRS Definition of Refractory Glaucoma 

The following PDF represents a consensus recommendation on behalf of the American Glaucoma Society (AGS), the American Society of Cataract and Refractive Surgery (ASCRS), and the American Academy of Ophthalmology (AAO).

Joint Letter - Defining Refractory Glaucoma

January 24, 2020

American Glaucoma Society Position Paper:

Microinvasive Glaucoma Surgery (MIGS)

Ronald L. Fellman, MD¹; Cynthia Mattox, MD²; Kuldev Singh, MD³; Brian Flowers, MD⁴; Brian A. Francis, MD, MS⁵; Alan L. Robin, MD⁶; Michelle R. Butler, MD¹; Manjool M. Shah, MD⁶; JoAnn A. Giaconi, MD⁵; Arsham Sheybani, MD⁷; Brian J. Song, MD, MPH⁸; Joshua D. Stein, MD, MS⁶

¹Glaucoma Associates of Texas, Dallas TX; ²Tufts University School of Medicine, Boston, MA; ³Stanford University, Palo Alto, CA; ⁴Ophthalmology Associates of Fort Worth, Fort Worth, TX; ⁵University of California – Los Angeles, Los Angeles, CA; ⁶University of Michigan, Ann Arbor, MI; ⁷Washington University, St. Louis, MI; ⁸Southern California Permanente Medical Group, Ontario, CA.

In 2018, the American Glaucoma Society (AGS), the world’s largest professional society of glaucoma subspecialists, convened a 12-member task force of experts to craft a Position Statement about Microinvasive Glaucoma Surgery (MIGS). The main objective of this Position Statement is to provide a succinct overview of these procedures and address some misconceptions about MIGS. The members of the task force were selected by the AGS Board of Directors and include AGS members with expertise in developing MIGS, teaching MIGS, performing research on utilization and outcomes of these procedures, and working with the U.S. Food and Drug Administration and other regulatory agencies about developing criteria to evaluate the efficacy and safety of these devices. Each of the sections of the Position Statement was prepared by subgroups of the task force and then the material from the various sections were aggregated and the leader of the task force (JDS) merged the material into a cohesive draft.  This draft was shared with the AGS Executive Committee and other members of the AGS Board of Directors for additional input.    

Overview and Definition of MIGS

Glaucoma is a group of chronic, often asymptomatic diseases that damage the optic nerve in a characteristic manner and, if left untreated or insufficiently treated, can lead to irreversible disability, vision loss, and blindness. In the United States, vision loss due to glaucoma is a leading cause of disability and blindness in blacks, whites, Latinos, and Asian Americans.^1-4 The functional visual loss secondary to glaucoma is often measured by static automated perimetry and correlated with the degree of structural disc damage measured by optic disc photography and optical coherence tomography. Key objectives in the management of glaucoma are to maximize health-related quality of life, preserve remaining visual function, as well as minimize future vision loss and the risks of treatment necessary to achieve these goals.

Currently, the only known way of slowing the rate of glaucomatous vision loss is by lowering intraocular pressure (IOP). This can be achieved with medications, laser procedures, or incisional procedures. Medications are usually delivered as eye drops. While medications can be effective at lowering IOP, they can be expensive and difficult to administer. Nearly two-thirds of patients are unable to administer eye drops correctly and more than one-half of all patients with glaucoma struggle with medication adherence.⁵ Self-administration of eye drops can be quite difficult for many patients with glaucoma, and a large proportion of these patients live without a support structure to assist them.^6,7 Moreover, a single class of IOP-lowering medication is inadequate to control the IOP in more than 50% of all patients with glaucoma.⁸ While it is possible to add additional classes of IOP-lowering medications, complex medication regimens frequently result in non-adherence, which in turn can lead to disease progression. Traditional incisional glaucoma procedures (i.e. trabeculectomy or aqueous shunt surgery) that create subconjunctival filtration blebs are often reserved for patients with progressive disease who are at high risk of severe vision loss. (Figure 1) These procedures can substantially lower IOP and preserve vision, but they themselves can decrease the quality of life and often require a lengthy recovery period, are subject to the vicissitudes of wound healing, and potentially have devastating complications.^8-19 In recent years there has been a push for alternative surgical approaches to lower IOP that reduce the need for glaucoma medications and some of the serious risks associated with traditional glaucoma procedures, such as hypotony (low IOP), choroidal effusion and/or hemorrhage, tube exposure, bleb leaks, blebitis, and endophthalmitis. Collectively this new class of procedures is known as microinvasive glaucoma surgery (MIGS). MIGS procedures are designed to lower IOP by improving aqueous outflow with minimal disruption to the sclera or conjunctiva with or without an implanted device, or by reducing aqueous production selectively. Outflow enhancement can be accomplished by facilitating access of aqueous humor to Schlemm’s canal (canal-based), the suprachoroidal space, or the subconjunctival space. Reducing aqueous production can be accomplished through selective direct laser ablation of the ciliary processes, the structures that produce the aqueous humor.

Comparison of MIGS to Traditional Incisional Glaucoma Surgeries

All surgical procedures, including those for glaucoma, carry risks of adverse events. These risks must be carefully weighed against the expected benefits of preserving vision and quality of life. Many members of the AGS have enthusiastically supported the development of MIGS, particularly for the treatment of subsets of patients whose risk of vision loss from glaucoma progression may not justify the risk associated with traditional filtration surgery or aqueous shunt implantation. The non-trivial risk of vision loss associated with these traditional glaucoma procedures often outweighs the potential benefit of lowering IOP, discouraging ophthalmologists from recommending these procedures and patients from consenting for them except in relatively dire circumstances, even when they may help stabilize the disease.

Unlike traditional glaucoma procedures, canal-based MIGS can often be performed with smaller incisions, akin to those used during modern day cataract surgery. Most of these procedures enhance the physiologic outflow pathways of the eye, which results in a safer lowering of IOP. Patients with ocular hypertension who are at high risk for experiencing vision loss due to uncontrolled IOP or with early-stage glaucoma, but who cannot tolerate or afford medical treatment, might be excellent candidates for MIGS procedures. Likewise, patients with moderate- to severe-stage glaucoma whose ocular or medical comorbidities make them less than ideal candidates for traditional glaucoma surgery might also benefit.  Fewer postoperative visits make these procedures excellent options for working-age patients and elderly patients who may rely upon working-age relatives to bring them to perioperative appointments.

Canal-based MIGS lower IOP by improving outflow through the patient’s natural drainage system instead of creating a bleb (a subconjunctival reservoir from which aqueous humor can slowly egress and thereby lower IOP) to capture the aqueous.²⁰ This considerably enhances the safety profile and limits discomfort, which can be an issue with traditional glaucoma procedures. Patients who are deemed to not be good candidates for canal-based MIGS may still be candidates for subconjunctival MIGS, a less invasive form of classic filtration surgery that utilizes microstents to create a bleb.^20,21 Other potential advantages of MIGS over traditional glaucoma procedures include faster recovery, less impact on leisure activities (such as swimming), and reduced risk of damaging other structures in the eye that can necessitate additional ocular surgeries. While many patients with different types and severities of glaucoma can benefit from MIGS, some patients clearly fare better with traditional glaucoma filtration surgery, so it is important to have all of these procedures available to allow the surgeon and patient together to decide which intervention is most appropriate.

Categorization of Different MIGS Procedures

Most MIGS lower IOP by reducing outflow resistance. To accomplish this, the surgeon may dilate, cleave open, or bypass abnormally resistant tissue that is hindering outflow or insert a device into an outflow structure or space to enhance the drainage of aqueous. These procedures may be divided broadly into bleb-forming and non-bleb-forming procedures.²⁰ Bleb-forming MIGS are placed through an ab-externo (outside of the eye) or ab-interno (inside of the eye) approach while all non-bleb forming MIGS are performed ab-interno. These devices may be further categorized based on the anatomical location of device placement or tissue manipulation. This categorization aligns with Current Procedural Terminology (CPT-4) coding as outlined in Figure 1. 

Complexity of MIGS Procedures

In general, intraocular surgery is a complex task as it involves working in very small spaces, adjacent to sensitive structures, where missteps can lead to permanent vision loss. The learning curve can be quite long and difficult. Residency and fellowship training forms the basis of the acquisition of these skills. Performing MIGS requires an even higher skill level as it requires the use of gonioprism mirrors under an operating microscope to visualize the ocular structures that require treatment, working in even smaller more sensitive spaces within the eye, and requires learning a new proprioceptive skill, namely intraoperative surgical gonioscopic viewing of the angle. This particular skill requires more manual dexterity as the surgeon must use one hand to balance the gonioprism on the cornea to permit visualization of the structures requiring treatment and simultaneously the second hand to carry out the procedure. Although gonioscopy is used to classify and diagnose glaucoma at the slit lamp in all patients with glaucoma, the skills required at the surgical microscope are usually more difficult to master. Those with experience training new surgeons in these techniques have observed that some new surgeons can adapt to these increased demands, but many cannot. It may seem paradoxical that a safer surgical procedure with fewer complications tends to require more manual dexterity involving both hands simultaneously, better anatomic knowledge, and be more technically demanding to perform. However, this is actually relatively common in medicine as evidenced in the transition from open to laparoscopic surgery and the transition from intracapsular cataract surgery to extracapsular cataract surgery to phacoemulsification. 

Preoperative Considerations

As with any surgical procedure, a prerequisite to the success of MIGS involves a thorough preoperative assessment to ensure the patient is an appropriate candidate for a given procedure, to select which procedure is most likely to succeed for a particular patient, and to be certain that the benefits of the surgery outweigh its risks. There are many nuances of these surgeries that must be considered to achieve optimal results. For example, careful examination of the anterior chamber angle is of paramount importance. If a MIGS procedure is combined with cataract surgery, it is also very important to evaluate for conditions that may increase the complexity of the surgery such as peripheral anterior synechiae, conjunctival scarring, angle visibility, and zonular instability. In addition, determining the site from which to approach a given procedure, for example ab interno or ab externo, requires careful consideration, as it may affect the options available for subsequent glaucoma surgery. Another preoperative consideration is the provision of thorough informed consent to the patient. During such a discussion, the surgeon should acknowledge the fact that long-term outcomes for many MIGS procedures are not yet known and there may be unanticipated risks associated with these surgeries. 

Postoperative Considerations

The postoperative period after some MIGS procedures is generally much easier on patients than after traditional glaucoma surgeries. Discomfort from conjunctival sutures is less frequent (since sutures are not needed for many MIGS) and visual recovery tends to be quicker than with traditional incisional glaucoma procedures. However, careful postoperative care is still required to achieve good outcomes as patients undergoing MIGS are more prone to postoperative complications such as IOP spikes, device movement or erosion, hyphema, and corticosteroid-induced elevation of IOP relative to other patients who undergo cataract surgery alone.²² As such, it is important to educate the patient of the importance of postoperative care, to help ensure the success of the procedure.

Considerations for Clinical Trial Design for MIGS

There is no one ideal therapeutic approach that applies to every patient with glaucoma. Glaucoma therapy must be tailored based upon weighing the risk and benefit of the various treatment options, taking a patient’s disease state and projected course into careful consideration. Given the variability in the effectiveness, safety profile, patients’ responses to different therapies, and patients’ perceptions of the relative importance of the various risks and benefits, glaucoma care very much remains a mixture of art and science.

“Maximum tolerated medical therapy” and “refractory glaucoma” are ambiguous terms that may be confusing when integrated into clinical practice guidelines and policy statements. Differences in interpretation of these terms can also result in ambiguity in determining patients who may be eligible for different MIGS procedures. To help provide clarification, the AGS defines the terms as follows:

“Maximum tolerated medical therapy” (MTMT) is attained once the patient is successfully using the greatest number of topical glaucoma medication classes he or she can tolerate and that add additional IOP reduction. For some patients that could be as many as 6 or more different classes of glaucoma medications taken daily, and for others it is no medications at all. Medication intolerance can be attributed to a variety of reasons ranging from expense, side effects, and an inability to administer eye drops. As mentioned earlier, non-adherence to glaucoma medications for any of the above reasons can cause permanent vision loss as the disease progresses. In some patients, the clinical presentation is so severe that incisional surgery is the most appropriate initial intervention, even forgoing medical treatment.

“Refractory glaucoma” is simply glaucoma that is difficult to treat and poorly controlled by current therapy, regardless of the stage of disease. Stage of disease as defined in the literature and based on the ICD-10 coding system designates the amount of damage to the visual system from glaucoma at a moment in time. All patients have a risk of progressing to worsening stages of glaucoma damage over time if their glaucoma is not controlled. There are a variety of reasons why a particular patient’s glaucoma may be difficult to treat, ranging from an inability to properly adhere to the medical management plan, inability to instill eye drops, poor responsiveness of the eye to IOP-lowering interventions, systemic side effects, or the presence of scar tissue from prior injury or surgery.

Historically, treatment options have involved topical medications and laser trabeculoplasty for patients with mild to moderate disease. Riskier surgical approaches are usually reserved for those with more advanced glaucoma, those who are at higher risk of losing visual function, or who fail less invasive options. There has been a large void with regard to surgical options for patients who are unable or unwilling to take glaucoma medications, and for those with mild yet progressive disease in whom medications and laser fail to sufficiently control IOP, but the disease severity level does not justify the inherent risks of traditional incisional glaucoma surgery. The availability of MIGS devices has afforded more therapeutic options to address this large segment of patients with glaucoma. The FDA and the AGS have since come together for workshops and discussions to advance these innovations to serve patients with glaucoma. Unfortunately, given the absence of an appropriate predicate device, the FDA premarket approval pathway (PMA) for many implantable MIGS devices has been very expensive, time consuming, and sometimes frustrating for researchers and companies trying to innovate in this area. In the case of ab interno MIGS implants, the devices were required by the FDA to be implanted at the time of concomitant cataract surgery. This was partly to investigate the IOP-lowering effect of cataract surgery alone in a control population, but also as a way to mitigate risk as recipients of the implants received the benefit of cataract surgery. Hence clinical indications on the labels for the ab interno implants all specify “with cataract surgery.” Another example applies to the “bleb-forming” MIGS, for which there are 3 ongoing trials (with more anticipated soon) of stand-alone MIGS procedures underway with the Ahmed (New World Medical Inc., Fontana, CA) glaucoma drainage device, a traditional glaucoma filtration surgery device, as the predicate device. Unfortunately, the study samples for these trials are required to be similar to those used in trials involving the predicate device. As such, these trials must be performed on patients labeled with “refractory glaucoma,” which has previously been defined by other groups as those that have failed at least one incisional glaucoma surgery. Yet the intended population who could most benefit from many MIGS surgeries is actually quite different from those who have already undergone incisional glaucoma surgeries. This study design with the requirement of failed prior surgery can greatly affect the results of the trial and create a potentially flawed process for evaluating these devices. The AGS recommends the FDA use the “de novo” (or other similar or novel) pathway for evaluating glaucoma devices with known (or anticipated) high levels of safety, such as most MIGS procedures. The AGS welcomes the opportunity to work with the FDA to develop appropriate protocols for trials and work through other logistical considerations to permit new MIGS devices to be evaluated in a fair manner on groups of patients with glaucoma who would better align with the intended target population when such devices are approved for marketing. 

The AGS believes that as data accumulate from completed PMA studies for various MIGS, there needs to be greater flexibility with respect to expanding the indication of already approved devices.  Furthermore, the introduction of next generation MIGS devices (where prior data is undoubtedly useful, particularly with regard to safety) should not be a static process but instead should permit developers of these devices the flexibility of the 510K pathway for “refractory glaucoma”. There are several different approaches that could allow for such flexibility. One option would involve redefining and expanding the criteria for what constitutes “refractory glaucoma” for purposes of the regulatory process, the same way that AGS defines this condition, as described above. Another option would be to create a parallel 510K pathway with previously approved MIGS device as a historical predicate, as noted in the aforementioned paragraph. We believe that regulatory authorities should engage the AGS, either via the existing network of experts, or via other formal associations, to outline the appropriate clinical trial designs necessary for clearance of the next generation of MIGS devices, as well as for expansion of indications for already approved devices. 

In contrast to other regions in the world, regulatory decisions in the United States have historically been separated from those related to reimbursement. The AGS believes that patients and their doctors might be better served if the information gathered by regulatory authorities in the clearance and labelling of innovative products (such as MIGS) was readily available to the authorities that make determinations about reimbursement. This could expedite the availability of these less invasive micro-incisional devices to patients for whom they would be beneficial. A related issue that often limits patients’ access to these MIGS procedures is that payors may only permit patients to undergo these procedures if they precisely fit the profile of those who received such a procedure during the FDA approval process. For example, because most of FDA trials involving MIGS have been performed on patients receiving these devices in combination with cataract surgery, several payors will only approve reimbursement of these procedures in patients who receive them concurrently with cataract surgery, despite the additive IOP-lowering effect of the implants observed in the clinical trials. This can be very problematic, especially for patients who either have no cataract or have already had their cataracts removed but might still benefit from these MIGS devices as stand-alone procedures.

Conclusion

With the rapidly rising number of patients with glaucoma in the United States and worldwide, it is essential for researchers and industry to continue developing innovative therapeutic options that are effective at lowering IOP, possess a good safety profile, and are well tolerated by patients. The advent and evolution of MIGS has increased the therapeutic options for patients with glaucoma, but there is still considerable room for improvement in the surgical delivery of glaucoma care. The AGS supports efforts that facilitate patient access to these procedures and that permit the clinician and patient to jointly decide which intervention(s) along the entire spectrum of care are best for them based on their unique circumstances.

References

1. Friedman DS, Wolfs RC, O'Colmain BJ, et al. Prevalence of open-angle glaucoma among adults in the United States. Arch Ophthalmol. 2004;122(4):532–538.

2. Quigley HA, West SK, Rodriguez J, Munoz B, Klein R, Snyder R. The Prevalence of Glaucoma in a Population-Based Study of Hispanic Subjects: Proyecto VER. Arch Ophthalmol. 2001;119(12):1819–1826.

3. Varma R, Wang D, Wu C, et al. Four-year incidence of open-angle glaucoma and ocular hypertension: the Los Angeles Latino Eye Study. Am J Ophthalmol. 2012;154(2):315–325.e1.

4. Stein JD, Kim DS, Niziol LM, et al. Differences in rates of glaucoma among Asian Americans and other racial groups, and among various Asian ethnic groups. Ophthalmology. 2011 Jun;118(6):1031-7.

5. Hennessy AL, Katz J, Covert D, et al. A video study of drop instillation in both glaucoma and retina patients with visual impairment. Am J Ophthalmol. 2011;152(6):982–988.

6. Tsai T, Robin AL, Smith JP3rd. An Evaluation of how Glaucoma Patients use topical medications: A Pilot Study. Trans Am Ophthalmol Soc. 2007;105:29-33; discussion 33-5.

7. The Advanced Glaucoma Intervention Study (AGIS): 3. Baseline characteristics of black and white patients. Ophthalmology. 1998 Jul;105(7):1137-45.

8. 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;118:1766-1773.

9. Gedde SJ, Heuer DK, Parrish RK 2nd; Tube Versus Trabeculectomy Study Group. Review of results from the Tube Versus Trabeculectomy Study. Curr Opin Ophthalmol. 2010 Mar;21(2):123-8.

10. Fontana H, Nouri-Mahdavi K, Lumba J, Ralli M, Caprioli J. Trabeculectomy with mitomycin C: outcomes and risk factors for failure in phakic open-angle glaucoma. Ophthalmology. 2006 Jun;113(6):930-6.

11. Kim HY, Egbert PR, Singh K. Long-term Comparison of Primary Trabeculectomy With 5-Fluorouracil Versus Mitomycin C in West Africa. J Glaucoma. 2008 Oct-Nov;17(7):578-83.

12. Wong MH, Husain R, Ang BC, Gazzard G, Foster PJ, Htoon HM, et al. The Singapore 5-fluorouracil trial: intraocular pressure outcomes at 8 years. Ophthalmology. 2013 Jun;120(6):1127-34.

13. Robin AL, Ramakrishnan R, Krishnadas R, Smith SD, Katz JD, Selvaraj S et al. A long-term dose-response study of mitomycin in glaucoma filtration surgery. Arch Ophthalmol. 1997 Aug;115(8):969-74.

14. Jampel H. Trabeculectomy: more effective at causing cataract surgery than lowering intraocular pressure? Ophthalmology. 2009 Feb;116(2):173-4.

15. Wong TT, Khaw PT, Aung T, Foster PJ, Htoon HM, Oen FT, et al. The singapore 5-Fluorouracil trabeculectomy study: effects on intraocular pressure control and disease progression at 3 years. Ophthalmology. 2009 Feb;116(2):175-84.

16. Stein JD, Ruiz D Jr, Belsky D, Lee PP, Sloan FA. Longitudinal rates of postoperative adverse outcomes after glaucoma surgery among medicare beneficiaries 1994 to 2005.

Ophthalmology. 2008 Jul;115(7):1109-1116.

17. Palanca-Capistrano AM, Hall J, Cantor LB, Morgan L, Hoop J, WuDunn D. Long-term outcomes of intraoperative 5-fluorouracil versus intraoperative mitomycin C in primary trabeculectomy surgery. Ophthalmology. 2009 Feb;116(2):185-90.

18. Shigeeda T, Tomidokoro A, Chen YN, Shirato S, Araie M. Long-term follow-up of initial trabeculectomy with mitomycin C for primary open-angle glaucoma in Japanese patients. J Glaucoma. 2006 Jun;15(3):195-9.

19. Gedde SJ, Herndon LW, Brandt JD, Budenz DL, Feuer WJ, Schiffman JC; Tube Versus Trabeculectomy Study Group. Postoperative complications in the Tube Versus Trabeculectomy (TVT) study during five years of follow-up. Am J Ophthalmol. 2012 May;153(5):804-814.

20. Schehlein EM, Kaleem MA, Swamy R, Saeedi OJ. Microinvasive Glaucoma Surgery: An Evidence-Based Assessment. Expert Rev Ophthalmol. 2017;12(4):331–343.

21. Chatzara A, Chronopoulou I, Theodossiadis G, Theodossiadis P, Chatziralli I. XEN Implant for Glaucoma Treatment: A Review of the Literature. Semin Ophthalmol. 2019;34(2):93-97.

22. Yook E, Vinod K, Panarelli JF. Complications of micro-invasive glaucoma surgery. Curr Opin Ophthalmol. 2018 Mar;29(2):147-154.

Disclosures

Fellman: Consultant: Alcon, Beaver Visitech Inc.; Honorarium: Aerie, Bausch and Lomb; Research support: Ivantis, Glaukos; Mattox: Consultant: Aerie, Alcon, Allergan, Glaukos, Ivantis, New World Medical, Santen, Zeiss Meditec; Singh: Consultant:  Alcon, Allergan, Glaukos, Ivantis, Santen, Sight Sciences; Flowers: Consultant: Alcon, Ivantis, Sun Pharmaceuticals, Bausch and Lomb, InnFocus, Sight Science, New World Medical, iStar, EyeNovia. Research support: Alcon, Ivantis, Glaukos, Aerie, InnFocus, Sight Science, iStar, Santen; Francis: Consultant: Neomedix, Glaukos, Beaver Visitech; Research Support: Santen, Allergan, iStar; Speaker: Aerie, Bausch and Lomb; Robin: Consultant: Google AI; Butler: Speaker: Allergan; Shah: Consultant: Allergan, Glaukos, Katena; Speaker: Allergan; Giaconi:  Speaker: Allergan; Sheybani: Consultant: Allergan, Katena, Ivantis; Speaker: Glaukos, Allergan

Song: None; Stein: None

Prepared by Henry Jampel, M.D., M.H.S.
August 10, 2009

Glaucoma is a disease of the optic nerve that can result in vision loss and blindness.  Although many factors, some only partially understood, contribute to the optic nerve damage in glaucoma patients, it has been definitively established that the level of intraocular pressure (IOP) is related to the presence of damage1, and that treatments that lower IOP reduce the risk of developing initial damage2, and slow the progression of  preexisting damage3.  Therefore, the mainstay of treatment for glaucoma patients is lowering the IOP.

There are three modalities in widespread use for the lowering of IOP: medications, laser treatment, and operating room surgery.  Although historically, systemic medications in the form of oral carbonic anhydrase inhibitors had an important long term role in lowering the IOP, their side effects have resulted in their almost total replacement by many classes of effective eye drops with many fewer side effects.

Despite the treatments available for lowering the IOP, there are some individuals for whom these treatments are either not tolerated due to side effects or in whom the IOP is not sufficiently lowered.  In these situations, both glaucoma patient and physician look for alternative therapies.

One of the commonly discussed alternatives for the treatment of glaucoma by lowering IOP is the smoking of marijuana.  It has been definitively demonstrated, and widely appreciated, that smoking marijuana lowers IOP in both normal individuals and in those with glaucoma, and therefore might be a treatment for glaucoma4,5.  Less often appreciated is marijuana’s short duration of action (only 3-4 hours), meaning that to lower the IOP around the clock it would have to be smoked every three hours.  Furthermore, marijuana’s mood altering effects would prevent the patient who is using it from driving, operating heavy machinery, and functioning at maximum mental capacity.  Marijuana cigarettes also contain hundreds of compounds that damage the lungs, and the deleterious effect of chronic, frequent use of marijuana upon the brain is also well established5.

Other means of administering the active ingredient of marijuana, tetrahydrocannabinol (THC), include oral, sublingual, and eye drop instillation.  The first two avoid the deleterious effect of marijuana smoke on the lungs, but are limited by the other systemic side effects.  In one study in which doctors offered some of their patients with worsening glaucoma the option of pills containing tetrahydrocannabinol and/or smoking marijuana, 9 of 9 patients had discontinued use by either or both methods within 9 months due to side effects6.  Given that glaucoma is a lifelong disease, commonly requiring treatment for decades, these results strongly suggest that systemic use of THC is not a reasonable treatment option for such patients.  The use of eye drops containing THC, or related compounds, has been investigated, but it has not yet been possible to formulate an eye drop that is able to introduce the drug into the eye in sufficient concentrations due to the low water solubility of the active ingredients.

Although marijuana does lower the IOP temporarily, IOP lowering is only one consideration in slowing the optic nerve damage of glaucoma.  For instance, there is a growing body of evidence that inadequate blood supply to the optic nerve may contribute to glaucoma damage.  Since marijuana given systemically is known to lower blood pressure, it is possible that such an effect could be deleterious to the optic nerve in glaucoma, possibly reducing or eliminating whatever beneficial effect that conferred by lowering IOP.   For this reason, marijuana, or its components administered systemically, cannot be recommended without a long term trial which evaluates the health of the optic nerve.ADDIN RW.CITE7

An exciting finding in the past decade is the discovery of receptors for the active components of marijuana in the tissues of the eye itself, suggesting that local administration has the possibility of being effective8.  Furthermore, there is evidence from research in the brain that there may be properties of the cannabinoid components of marijuana that protect nerve cells like those in the optic nerve9.  This raises the hope that marijuana or related compounds could protect the optic nerve not only through IOP lowering but also through a neuroprotective mechanism.  However, unless a well tolerated formulation of a marijuana-related compound with a much longer duration of action is shown in rigorous clinical testing to reduce damage to the optic nerve and preserve vision, there is no scientific basis for use of these agents in the treatment of glaucoma.

Summary: Although marijuana can lower the intraocular pressure (IOP), its side effects and short duration of action, coupled with a lack of evidence that it use alters the course of glaucoma, preclude recommending this drug in any form for the treatment of glaucoma at the present time.

References:

1. Coleman AL, Miglior S. Risk factors for glaucoma onset and progression. Surv Ophthalmol. 2008;53 Suppl1:S3-10. 
2. 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;120:701-13; discussion 829-30. 
3. 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;120:1268-1279. 
4. Merritt JC, Crawford WJ, Alexander PC, Anduze AL, Gelbart SS. Effect of marihuana on intraocular and blood pressure in glaucoma. Ophthalmology. 1980;87:222-228. 
5. Green K. Marijuana smoking vs cannabinoids for glaucoma therapy. Arch Ophthalmol. 1998;116:1433-1437. 
6. Flach AJ. Delta-9-tetrahydrocannabinol (THC) in the treatment of end-stage open-angle glaucoma. Trans Am Ophthalmol Soc. 2002;100:215-22; discussion 222-4. 
7. Kaufman PL. Marijuana and glaucoma. Arch Ophthalmol. 1998;116:1512-1513. 
8. Jarvinen T, Pate DW, Laine K. Cannabinoids in the treatment of glaucoma. Pharmacol Ther. 2002;95:203-220. 
9. Nucci C, Bari M, Spano A, et al. Potential roles of (endo)cannabinoids in the treatment of glaucoma: From intraocular pressure control to neuroprotection. Prog Brain Res. 2008;173:451-464. 

American Glaucoma Society
BOD Approved – 10.23.2009

Adriana L. Grossman, Matthew J. Javitt, Steven J. Moster, and Alana L. Grajewski on behalf of Pediatric Glaucoma Subcommittee of the American Glaucoma Society (2017-2018)*

Pediatric glaucoma refers to a group of conditions in which elevated intraocular pressure leads to damage of the developing eye in infancy and early childhood.  In addition to anatomic effects specific to children, particularly ocular enlargement, elevated eye pressure at any age can damage the optic nerve resulting in vision loss. Ophthalmologists face challenges choosing appropriate treatment modalities to prevent childhood blindness. Standard treatment for most childhood glaucoma types includes surgical intervention. Medical management is a primary treatment and is used in conjunction with surgical intervention in all pediatric glaucoma types, but surgery and/or exams under anesthesia are an integral part of the treatment for infants and children with glaucoma. In an effort to avoid surgery and/or the frequent exposure to anesthesia, many parents and patients seek other, nonstandard options including cannabinoids. 

Cannabinoid receptors play a role in appetite, pain, mood and memory in the body. Type 1 receptors (CB1) are located in the central nervous system, lungs and kidneys. These animal studies have shown both neuroprotective effects^1,2 and neurotoxicity² when cannabinoids are administered after experimental nerve injury. A systematic review of randomized controlled trials³ identified one very small trial which showed a short term ocular hypotensive effect of one of three tested cannabinoids when administered as an oromucosal spray.⁴ To date, other studies showing positive effects have also found that pressure reduction lasts only a few hours, which would require dosing schedules that would limit clinical utility. A recent study showed that cannabidiol (CBD), the cannabinoid that has shown effectiveness as an anti-epileptic, increased IOP in mouse models by inhibiting CB1 activation. Moreover, the transient hypotensive effects shown in previous studies were attributed to the more psychoactive cannabinoid, tetrahydrocannabinol (THC).  Achieving therapeutic hypotensive effects of cannabis may therefore require frequent dosing with the most hallucinogenic ingredients.⁵ In summary, there is limited evidence that medical cannabinoids are currently an effective treatment for improving intraocular pressure associated with glaucoma. 

Many studies suggest that early cannabinoid use during adolescence, usually defined as use before age 16, is associated with subsequent neurocognitive development.⁶ A birth cohort of 1037 individuals who underwent neurophysiological testing before cannabis use and at intervals up to age 38 compared those cohort members who became regular cannabis users to non-users or irregular users. The persistent cannabis users showed neuropsychological decline broadly across several domains of functioning with trends toward lower IQ even after controlling for years of education.⁷ Radiographic studies of regular cannabis users and non-users found changes in white matter development in early onset users compared to later onset users and non-users. Early onset users also demonstrated cognitive deficits in executive functioning and increased impulsivity.⁸ Early use of cannabinoids during adolescence is associated with a disproportionate prevalence of users having psychiatric disorders, such as schizophrenia,⁹ psychotic symptoms,¹⁰ future substance abuse¹¹ and depression in adulthood.¹² At this point, the clinical and preclinical literature on early exposure to cannabis do not prove causality, but early use is correlated with neurocognitive developmental changes and affective outcomes in adulthood. 

The American Medical Association recognizes the potential utility of marijuana in certain conditions. They include treatment for adults with chemotherapy-associated nausea and vomiting, cachexia, and certain neurological conditions such as spasticity associated with multiple sclerosis. Data on its effectiveness in pediatric populations are limited to its role in decreasing seizures in recalcitrant epilepsy.¹³ Currently the American Academy of Pediatrics does not support the use of marijuana in patients under 21 given the possible adverse health and brain development.¹⁴ However, it does recognize that it may be used as an option for children with life-limiting or severely debilitating conditions that are unresponsive to current therapies. 

There are currently no studies on the effects of cannabinoids on intraocular pressure in the pediatric population. There are unclear but potential negative neurocognitive developmental implications in pediatric patients utilizing cannabinoids. Current medical and surgical management to stop the progression of glaucoma is effective. The American Glaucoma Society does not support the use of cannabinoids for treatment of pediatric glaucoma. 

*Pediatric Glaucoma Subcommittee Members:

Allen D. Beck, MD

Lauren S. Blieden, MD

Elena Bitrian, MD

Ta C. Chang, MD

Elizabeth Hodapp, MD

Keren M. Joos, MD

Bibiana J. Reiser, MD

Angelo P Tanna, MD

References

1. Yoles E, Belkin M, Schwartz M. HU-211, a nonpsychotropic cannabinoid, produces short- and long-term neuroprotection after optic nerve axotomy. J Neurotrauma. 1996;13:49–57.

1. Sarne Y and Mechoulam R. Cannabinoids: Between Neuroprotection and Neurotoxicity. Curr Drug Targets CNS Neurol Disord. 2005 Dec;(4):667-684.
2. Whiting PF, Wolff RF, Deshpande S, et al. Cannabinoids for Medical Use: A Systematic Review and Meta-analysis. JAMA. 2015 Jun 23-30;313(24):2456-73.
3. Tomida I, Azuara-Blanco A, House H, et al. Effect of sublingual application of cannabinoids on intraocular pressure: a pilot study. J Glaucoma. 2006 Oct;15(5):349-53.
4. Miller S, Daily L, Leishman E, et al. D9-Tetrahydrocannabinol and Cannabidiol Differentially Regulate Intraocular Pressure. Invest Ophthalmol Vis Sci. 2018 Dec;59(15):5904-5911.
5. Levine A, Clemenza K, Rynn M, et al. Evidence for the Risks and Consequences of Adolescent Cannabis Exposure. J Am Acad Child Adolesc Psychiatry. 2017 Mar;56(3):214-225.
6. Meier MH, Caspi A, Ambler A, et al. Persistent cannabis users show neuropsychological decline from childhood to midlife. Proc Natl Acad Sci U S A. 2012 Oct 2;109(40):E2657-64.
7. Gruber SA, Dahlgren MK, Sagar KA, et al. Worth the wait: effects of age of onset of marijuana use on white matter and impulsivity. Psychopharmacology (Berl). 2014 Apr;231(8):1455-65.
8. Galvez-Buccollini JA, Proal AC, Tomaselli V, et al. Association between age at onset of psychosis and age at onset of cannabis use in nonaffective psychosis. Schizophr Res. 2012;139:157-160.
9. Moore THM, Zammit S, Lingford-Hughes A, et al. Cannabis use and risk of psychotic or affective mental health outcomes: a systematic review. Lancet. 2007;370:319-328.
10. Mayet A, Legleye S, Falissard B, Chau N. Cannabis use stages as predictors of subsequent initiation with other illicit drugs among French adolescents: use of a multi-state model. Addict Behav. 2012;37:160-166.
11. Womack SR, Shaw DS, Weaver CM, Forbes EE. Bidirectional associations between cannabis use and depressive symptoms from adolescence through early adulthood among at-risk young men. J Stud Alcohol Drugs. 2016;77:287-297.
12. Stockings E, Zagic D, Campbell G, Weier M, Hall WD, Nielsen S, Herkes GK, Farrell M, Degenhardt L. Evidence for cannabis and cannabinoids for epilepsy: a systematic review of controlled and observational evidence. J Neurol Neurosurg Psychiatry. 2018 Mar 6. pii: jnnp-2017-317168. doi: 10.1136/jnnp-2017-317168. [Epub ahead of print]

Ammerman S, Ryan S, Adelman WP, et al. The impact of marijuana policies on youth: clinical, research, and legal update. Pediatrics. 2015 Mar;135(3):e769-85.

Approved by the AGS Board of Directors – June 18, 2019
American Glaucoma Society

The American Glaucoma Society (AGS) is an organization of over 700 fellowship-trained glaucoma surgeons in the United States whose mission is to promote excellence in the care of patients with glaucoma, and preserve or enhance vision by supporting glaucoma specialists and scientists through the advancement of education and research.The American Glaucoma Society (AGS) is an organization of over 700 fellowship-trained glaucoma surgeons in the United States whose mission is to promote excellence in the care of patients with glaucoma, and preserve or enhance vision by supporting glaucoma specialists and scientists through the advancement of education and research.

The AGS recognizes and supports its members who are working to advance the surgical care of glaucoma. Glaucoma filtration surgery, commonly performed as a trabeculectomy, is considered the gold-standard surgical procedure for patients who have failed medical or laser therapy, or who have advanced glaucoma because of its significant intraocular pressure lowering effect that serves to prevent further vision loss. However, glaucoma filtration surgery has been performed for over a hundred years with only minor modifications to the technique as microsurgical instruments, suture material and wound healing adjuncts became available. While often successful in lowering intraocular pressure and slowing disease progression, glaucoma filtration surgery may be associated with early and late complications such as hypotony, bleb leaks, and bleb-related infections.

In recent years, technologies have become available that seek to avoid the complications of traditional filtration surgery by accessing the eye’s natural aqueous drainage pathways and enhancing them. These technologies specifically seek to avoid a filtration bleb that can be the source of infection, discomfort, and other problems. These technologies represent a shift in focus and skills, yet seek to accomplish the goal of lowering intraocular pressure sufficiently to prevent vision loss from glaucoma.

A new technology whose intraocular pressure lowering effect allows for a reduction in medications, or a reduction in the need for more advanced surgical care, or improves patient adherence to care, would provide advantages to glaucoma patients. If effective and safe, we believe that these benefits and the fact that these technologies will not have bleb-related complications would represent an “improvement in net health outcomes”.  In addition, some of these types of glaucoma surgical techniques still allow traditional filtration surgery to be performed in the future if necessary. The AGS supports the development of new technologies that will allow for effective and safer surgical management of glaucoma.

The AGS is a member of the World Glaucoma Association and has reviewed and endorsed a recent publication entitled:  The World Glaucoma Association Guidelines on Design and Reporting of Glaucoma Surgical Trials.  Please see the World Glaucoma Association Surgical Trials paper for more in-depth discussion of conducting surgical clinical trials.  

Given that traditional glaucoma filtration surgery has a well-documented literature of effectiveness and complications, the AGS has established criteria under which Case Series of new glaucoma surgical technologies may be evaluated.

Criteria for Proper Reporting of Case Series:

1. Case series should report on all patients undergoing a planned procedure, even if the procedure needed to be aborted.
2. Case series should have at least 1 year of follow-up on all patients reported (not just an average follow-up of 12 months).
3. Results should be reported as Kaplan-Meier or other life-table analysis and scatter plots. Definitions of success and failure should be unambiguously stated and determined a priori, and failures at any time point not censored for analysis at subsequent time points.
4. Case series results should be clearly divided into cases that underwent the investigated procedure alone, and the investigated procedure combined with cataract surgery. These two groups should not be reported together as a combined series, but should be reported separately for all outcome measures.  The most useful series will be reports on the investigated procedure as a therapy with consistent procedural techniques.
5. Important outcome measures are intraocular pressure and complications. Intraocular pressure results should indicate the number of eyes requiring IOP lowering medications postoperatively at various time points, as well as the number of medications.
6. Complication detection should be explained in detail in the report and should be determined at the outset of the study to include relevant, clinically significant complications. 

Comments on Surgeons and Subjects and Outcome Measures:

1. The AGS strongly urges all study authors and participants to fully disclose financial interests and funding for surgical trial reports.
2. The AGS recommends that a limited number of surgeons be involved in the early phase of refining a technique and teaching it to other surgeons. Once the technique is refined, at least 50 eyes should be compiled for an initial analysis.  Once the procedure is disseminated and in “widespread use”, an acceptable number of surgeons actively utilizing the technique might be defined as 15% of the clinical glaucoma specialists in the AGS. The AGS strongly encourages all surgeons involved in a new technology procedure to collect clinical information about their cases, in a standardized fashion.
3. Given that trabeculectomy is a relatively rare surgical procedure (only 30,000 annual cases in the Medicare population), and glaucoma drainage implants with far posterior plate reservoirs even rarer (less than 9000 annual Medicare cases), the AGS acknowledges that relatively small numbers of subjects will comprise surgical trial reports, and still be acceptable for evaluation of the technique.  An acceptable number of eyes enrolled in a case series reported out to at least 12 months of a technique meant to supplant or be an alternative to trabeculectomy might be 100. An acceptable number of eyes enrolled in a case series of previously operated eyes undergoing a far posterior aqueous drainage procedure might be 50. Although power calculations may be used to alter the necessary number of eyes required to show efficacy.
4. Successful outcome elements for new intraocular pressure lowering techniques may include an increased safety profile, or improvement in patient adherence and/or comfort, or reduction in medication use, or speed or simplify recovery, postoperatively,
5. Each new procedure should be compared to an appropriate control group based on the proposed or observed efficacy and safety profile, and need not be compared to trabeculectomy. For example, surgical techniques that are known to lower the intraocular pressure by modest amounts may still allow for an improvement in health outcomes and may necessitate a more appropriate comparison than trabeculectomy.
6. Some categories of new surgical devices and techniques are utilized at the time of concomitant cataract surgery. Cataract surgery alone has been shown to lower intraocular pressure. A control group of patients with similar entry criteria undergoing cataract surgery alone may be appropriate for these technologies. 

The AGS recognizes the limitations of surgical trial evaluations, but also strongly supports the investigation of new technologies to help our patients achieve effective and safe vision preservation.

Revised and Approved by the AGS BOD – February 29, 2012
BOD Approved – October 23, 2009
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Changes in our health care system continue to create unintended consequences for glaucoma patients who rely upon pharmaceutical benefit plans to provide their glaucoma medications. Eye drops are different than pills. Eye drops are difficult to administer by over 2/3 of patients with many having trouble accurately administering a single drop onto their eyes. Many of these patients are faced with the additional difficulties of early refill denials due to quantity restrictions, lack of access to certain medications due to limited formularies, and high out-of-pocket copays.

Chronic medical therapy of glaucoma is a critical and cost-effective first line of treatment. Gaps in the treatment of glaucoma can lead to vision loss and blindness. This statement is submitted on behalf of members of the American Glaucoma Society (AGS), an organization of over 700 ophthalmologists who specialize in glaucoma care and surgery, and the American Academy of Ophthalmology (Academy), the world’s largest association of over 29,000 eye physicians and surgeons. We are committed to providing optimum care for the glaucoma patient.

Pharmacy benefit programs with Medicare Part D, and non-Medicare commercial health insurance plans, typically have strict limitations on the frequency of medication refills prescribed for chronic conditions. Plans restrict patients from refilling medications earlier than the single month or 90-day refill date. The number of drops in various bottles of glaucoma medications is known, assuming a constant bottle angle and pressure on the bottle. Despite the fact that bottles may contain more drops than the labeled quantity, there are numerous reports of patients running out of drops prematurely and patients unable to obtain refills under their plans prior to the allowed refill date. The current monthly volumes of eye drops allowed by health plans are often inadequate due to common and inadvertent wastage of drops when eye drops are applied. Often this leads to patients either stretching out their eye drop prescription (e.g., taking a twice daily medication once a day) or discontinuing their use of eye drops until the next allowable refill under their drug plan; creating a gap in care where the patient’s disease may worsen.

The AGS and Academy are very concerned about inadequate access to necessary medication for chronic glaucoma treatment.  In 2009, and again in 2010, our organizations approached the oversight committee for the Medicare Part D drug plans and were able to effect changes that resulted in an easing of the refill restrictions.  Medicare Part D drug plans now allow an override of the refill limits when patients seek to refill their eye drop prescription at 70% of the predicted days of use, e.g., at day 21 for a 30-day supply. In addition, physicians can now request authorization for even earlier refills for patients in need.

Eight state ophthalmology societies have been successful in working with their state legislators to enact laws, enabling patients to refill their eye drop medications on demand for commercial drug plans as of 2014. While these activities have helped alleviate

some of the barriers to eye drop medication access in some populations, the AGS and Academy hope to eliminate refill access problems for all patients. The AGS and Academy entreat health insurers with pharmacy benefit plans, and their pharmacy benefit managers, to study this issue further and re-evaluate their refill policies for eye drop medications. The AGS and Academy would be delighted to assist with this process.

Formulary Management
Restricted and tiered formularies for glaucoma eye drop medications have become standard policy for all pharmaceutical benefit plans in Medicare Part D and commercial insurances. Various strategies are employed to incentivize patients and encourage providers to use the least expensive glaucoma medication. Some drugs are restricted by “quantity limits” and are subject to the concerns we described above. Other drugs are restricted by “step therapy” that requires physicians to prescribe and document the discontinuance of a lower-tier drug before allowing access to a higher-tier medication.  Finally, some drugs are placed in a prohibitively high-cost tier. Because each drug plan formulary is different, this information is often lacking to both the physician and patients until the patient presents their prescription to their pharmacist, although some electronic prescribing systems now provide tier-level information for some plans. Pharmacists, however, have direct patient-specific access to tier-level copay amounts, deductibles, drug plan prior authorization fax numbers and addresses, while physicians do not.  This limits our members’ ability to counsel patients about drug costs and restrictions.

Step-therapy often requires multiple interactions with the drug plan on the part of the physician to provide records, sometimes from many years prior, to prove to the plan that the patient has tried and failed a particular therapy. During this time-consuming process, the patient is denied access to needed medications.

A particularly troubling feature of formulary management is the ability for drug plans to switch tiers for their drugs on a yearly basis. The most common scenario is for brand name drugs within the same class to be moved back and forth from one tier to another, presumably due to the negotiated costs and rebates of the drug. The workflow cost to an insurer making a formulary tier change within class is negligible, while the cost to a physician’s practice is high. Managing phone calls from patients and pharmacists who want to avoid the higher copay or are concerned about a change in medication, rewriting and authorizing prescriptions, and educating patients and fielding their questions about a medication change and potential side effects is time-consuming and costly to a practice, while achieving no real benefit for the patient. In addition, if a change in medication is made, patients must return to the office for an earlier re-evaluation, increasing health care spending (often more than the price differential to the pharmacy plan).

The AGS and Academy ask the pharmacy benefit managers to carefully evaluate their formulary changes with these issues in mind, ensuring that both physicians and patients have timely access and reasonable cost for their glaucoma medications. Plans should consider a system whereby a patient who has had documented success with a particular medication in a prior year is allowed to continue at the same or lower tier-level copay in subsequent years.

In addition, the Academy, along with other medical organizations, has suggested that the Center for Medicare and Medicaid Services (CMS) create a billing code that would reimburse a physician whenever the practice is managing a drug prescription issue that develops solely due to a formulary change from an insurer.

Summary
In the United States, there are millions of patients treated with topical eye medications each year. In the treatment of glaucoma, almost 75% are treated with more than one medication simultaneously for long periods of time, often years. It has long been recognized that non-adherence is a significant roadblock to successful treatment of patients even when appropriate medications are easily available. Inadequately treated glaucoma leads to irreversible vision impairment and blindness. Although there are patients who are vigilant in taking their eye drops regularly and on schedule, ophthalmology is relatively unique, however, as even compliant patients may not be able to administer eye drops correctly and may waste a significant volume every day. Unlike pills, eye drops are difficult to use and are a less reliable drug delivery system. We have found that, even in experienced glaucoma patients who self-administer their eye drops, between 53–61% regularly administer more than one drop at a time, many without even realizing it. These numbers are increased in those with poor vision from glaucoma, cataract, or retinal diseases. Eighty percent of these patients with visual comorbidities are unable to adequately instill a single eye drop at a time.

Physical disabilities can also interfere with the administration of eye drops. It is particularly difficult for older patients to master and perform this task proficiently. Eye drop administration requires both the technical ability to easily squeeze out a single drop and the hand-eye coordination to find the eye and squeeze the drop onto the eye.  Regrettably, especially in older individuals where glaucoma is more common, diseases such as arthritis, tremor, Parkinson disease, and other neurological and musculoskeletal problems make it difficult to accurately squeeze the bottle to administer just a single drop. It is not uncommon for some patients to require double the allowed volume.

Ophthalmologists are increasingly aware that restrictions on medication availability are a component of poor outcomes in glaucoma treatment. It is well recognized that increased cost is associated with lack of adherence. Expecting the patient to pay full retail prices out-of-pocket for additional medication to cover the refill gap or for non-formulary medications is unrealistic, even if the patient is made aware that such an option exists.

High copays for drugs and increasingly popular high-deductible insurance plans will likely exacerbate patient concerns about drug costs in the future. Physicians and patients should have direct, easy access to all the cost information available for all drug plans in real-time, including links to online authorization portals for all drug plans.

Glaucoma patients who go untreated, even for relatively short periods of time, run the risk of worsening vision loss and increased likelihood of requiring surgical intervention for their disease. Surgical intervention carries far greater risk than chronic medical therapy and increases health care costs. Vision loss from glaucoma has been associated with an increase in the rates of falls, depression, difficulty with facial recognition, inability to drive, reading difficulty, reduced physical activity, and nursing home admissions.

The AGS and Academy entreat health insurers with pharmacy benefit plans and their pharmacy benefit managers to study these issues further and re-evaluate their refill and formulary tiering policies for eye drop medications. Strategies to increase eye drop availability should be immediately instituted to prevent interruption and gaps in treatment for our patients.

American Academy of Ophthalmology and American Glaucoma Society
July 2009 

BOD Approved – 09.01.2009; Revised and Approved – 01.2014
AAO, Quality of Care Secretariat – 09.2009; Revised and Approved – 01.2014

For patients to complain about glaucoma eye drop refill restrictions:

Call 1(800) Medicare (800 633-4227). 

You need your Medicare number, date of birth, and name of medication. You will hear an automated response system. Say or dial your Medicare number. 

There will be a prompt that asks you if you are dealing with a billing, claims, drug coverage problem, etc. Say, “drug problem”.  

You are then asked for your date of birth. After it confirms your date of birth, it confirms your prescription drug coverage or your supplemental insurance.  

The system will provide a number dealing with your drug coverage or supplemental insurance. Do not call that number yet. Instead you should stay on the line and say, “Agent”. After being on hold, a representative will pick up. The agent will ask you to confirm date of birth, name and address. The agent then will ask what the issue is. Tell them your experience. You should explain that you are not getting enough eye drop medications and that you run out before the next refill is allowed.  Explain that your doctor has already tried dealing with the issue, but you are still being denied the medication. 

Click here to see the 2010 CMS guidance document on early refills

May 19, 2011

To Whom It May Concern:

On behalf of the members of the American Glaucoma Society (AGS), we are writing to strongly support the continued use of the color code cap system for identification of classes of ophthalmic medications. The American Glaucoma Society is comprised of over 700 ophthalmologists who are fellowship-trained glaucoma specialists and surgeons.  The AGS has been in support of the American Academy of Ophthalmology (AAO) Position Statement supporting eye drop packaging color-coding. The Position Statement has been in place since 1983, and was most recently re-endorsed by the AAO in 2010. The standardized color-coding of bottle caps for eye drop medications has been a very effective aid for patients, their families, and practitioners to easily identify topical ophthalmic medications. In fact, the color-coding has been essential to enable visually impaired patients to independently manage and administer their own eye drop medications for chronic diseases such as glaucoma and uveitis.  In addition, using the color code system enhances patient – provider communication when assessing patient adherence with medication regimens.  We strongly advocate for maintenance, strengthening, and regulatory enforcement of the cap color-coding requirements currently in place.

We have learned that The American Association of Eye and Ear Centers of Excellence has initiated a proposal to eliminate the cap color coding of ophthalmic medications. This proposal, as articulated in a January 2010 letter to the Commissioner of the Food and Drug Administration, argued the opposition to ophthalmic color coding on grounds of patient safety. Citing examples of medication errors by pharmacists, hospital and clinic personnel, the AAEECE ascribes the “Look Alike Sound Alike (LASA)” issue to not only the labeling and bottle type of ophthalmic medications but also the color-coding of the caps. Although we understand that similarities in bottle shape and labeling (e.g. name and label font similarities) are a potential source of medication error, we strongly believe that color-coding of bottle tops actually enhances, not diminishes patient safety. We do, however, support enhancements to bottle and package labeling with larger font size for visually impaired patients.

In addressing patient safety issues in hospitals, pharmacies and healthcare facilities, attention is indeed necessary in the selection, use and handling of ophthalmic medications. Proper training for ophthalmic personnel, pharmacists, and nursing staff in the names, mode of action, and potential side effects of ophthalmic medications could be enhanced. For instance, personnel should be educated to recognize the differences in effects of the various dilating drops with red caps, and should be continually re-educated to habitually read the labels prior to administration or dispensing. In fact, reading the labels of all medications prior to administration or dispensing to a patient is an important safety precaution that should not be skipped, no matter what the color of the eye drop packaging.  In handling medications there is no replacement for appropriate education and training of health care workers at all levels.

Finally, while there have been case reports in the literature of patients inadvertently using non-ophthalmic medications in place of their ophthalmic preparations, errors were ascribed to bottle, bottle top shape, and label similarity^,. This issue has been addressed by placing red tips on bottles of drops that should not be administered in the eye, again providing a visual cue to the patient or care-giver.

For patients who take multiple topical medications with eye disease such as glaucoma, color-coding of the bottle tops is essential in assisting the patient in accurate administration of the medication. Patients who take multiple glaucoma medications or have other eye diseases may have significant vision loss and be unable to read labels accurately and must rely on top colors. Patients undergoing eye surgery are routinely prescribed several different postoperative eye drops and need to rely on eye drop color codes while their vision recovers. In addition, there are a significant number of Americans who are illiterate and may be unable to maintain adherence to their regimen without color-coded tops.  Color codes also allow for ophthalmic technicians and physicians to confirm which class of medications patients actually take, even if the patient cannot recall the medication name. Physicians routinely provide patients with medication schedule aids that reference the color codes as a way to enhance patient understanding and compliance. 

In summary, color-coding is used routinely and effectively by patients and physicians in clinical practice. Eliminating the important patient compliance aid of color-coded eye drop medications to avoid medication errors by properly trained health care workers seems misguided. While we are very concerned about the patient safety issue of inadvertent misuse of ophthalmic medications, the the American Glaucoma Society feels strongly that the color-code system for ophthalmic medications is a useful and necessary aspect of medication packaging which enhances patient safety, adherence, and outcomes. We support efforts to further differentiate packaging of ophthalmic preparations from other non-ophthalmic drops, but we do not support elimination of the color codes for topical ophthalmic medications.

Please contact us if you would like to discuss this issue further, or if we can provide any additional information. 

Sincerely,

Jeffrey Liebmann, MD (President, American Glaucoma Society)
Cynthia Mattox, MD (Chair, AGS Patient Care Committee)

References:

• Policy Statement: Color Codes for Topical Ocular Medications, 2010, American Academy of Ophthalmology 
• Fraunfelder, F.T. Drug-Packaging Standards for Eye Drop Medications. Arch Ophthalmol 1988;106:1029. 
• Ling, RTK et al Inadequacy of Current Labeling of Nonophthalmic Drops N Engl J Med 1989;320:62
• Budenz, D.L. A Clinicians Guide to the Assessment and Management of Nonadherence in Glaucoma. Ophthalmology 2009;116:s43-47

 2011

American Glaucoma Society Position Statement: Electronic Data Standards for Clinical Practice

Michael V. Boland, MD, PhD, Joel S. Schuman, MD, Cynthia G. Mattox, MD, and On behalf of the Patient Care Committee of the American Glaucoma Society

Click here to view PDF