Nathan Radcliffe, MD

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,” a blog series featuring contributions from members of the ophthalmic community. These blogs are an opportunity for ophthalmic bloggers to engage with readers with about a topic that is top of mind, whether it is practice management, experiences with patients, the industry, medicine in general, or healthcare reform. The series continues with this blog by 

. The views expressed in these blogs are those of their respective contributors and do not represent the views of 

At a time when there are more treatment options than ever to manage glaucoma-including new minimally invasive procedures and agents for medical treatment-the shortage of a traditional glaucoma drug is reminding us just how precarious our reliance on generics has become. Our supply of 

dorzolamide, long a first-line glaucoma therapy

 used alone or in fixed combination with timolol, has recently proven unreliable. We saw a shortage in fall 2017, and it seems to have returned now.
	
	

Shedding light on manufacturers of generics


	
	The dorzolamide shortages have revealed a lot about how generic molecules are supplied. Dorzolamide has about six different manufacturers whose supplies were disrupted at various times. The companies haven’t offered the reasons for the shortages, 

 shortages of the same drug are occurring among different manufacturers.
	
	The situation speaks to the fact that we don’t know exactly how generic drugs are manufactured overseas. Generic manufacturers also seem to have very little accountability to patients and to the physicians who prescribe the medications. They could shift production to a more profitable drug without answering to doctors and patients.
	
	In contrast, we’re appreciating the value of companies who manufacture brand-name medications. When manufacturing problems occur with branded drugs, most companies selling branded pharma are quick to inform doctors and patients of the reasons, when they expect to fix the problem, and what alternatives we can use in the interim.
	
	

When patients who take either dorzolamide or the fixed combination of dorzolamide and timolol try to fill their prescriptions, they are turned away at the pharmacy. Unable to get their medications, often patients don’t understand that they need to return to their physician to get a replacement, particularly if they have low health literacy. This is disruptive to care in many ways.
	
	Some patients will remain off the therapy until their next scheduled appointment. I have seen more than a handful of patients experience permanent vision loss after returning to the office with significant IOP elevations after going off of dorzolamide-timolol. Thus, there is a lapse in critical glaucoma medication for our patients.
	
	Doctors spend years educating patients with glaucoma about the importance of complying with medical therapy. Patients manage to develop some good habits with their medications, and they don’t need a shortage throwing a wrench in those efforts. During a shortage, they’re prescribed a new medication that may not be covered or well tolerated.
	
	To me, this is where the lack of accountability and commitment from generic manufacturers of dorzolamide is most damaging. Patients and physicians rely on these medications to prevent glaucoma-related blindness, and the companies that profit from those prescriptions are not honoring that need with a commitment to their customers.


	
	I want my patients with glaucoma to have consistent access to the medication I prescribe, without any disruption or negative experience at the pharmacy. This is essential to medical management of glaucoma. To avoid any problems from dorzolamide’s unpredictable availability today and in the future, I proactively stopped prescribing the drug to my patients whenever possible, either alone or in fixed combination.
	
	Tasked with choosing an alternative medication, we have to make the right choice for each patient in the context of their glaucoma status, overall health, other medications, and prescription drug coverage.
	
	The most logical alternative is 

), but coverage can present a roadblock. I have developed a decision tree (Figures 1 and 2) for my office staff that lays out the options. Essentially, 

 is often a reasonable substitution for dorzolamide, while 

 is an ideal substitution for dorzolamide-timolol shortages, assuming no brimonidine allergy.
	
	Certainly, the dorzolamide shortage has helped us view branded pharmaceutical companies in a positive light, given their commitment to transparency and to therapy for patients with glaucoma.
	
	With generic drugs undergoing price hikes and a variable supply, it’s often easier for doctors to find a treatment solution with a brand name we trust for patients with glaucoma. It will be interesting to see how the current dorzolamide shortage plays out and if we continue to see a lack of transparency and accountability among generic drug manufacturers in the future.

Dr. Radcliffe is a glaucoma specialist and professor at Icahn School of Medicine at Mount Sinai and New York and Ear Infirmary of Mount Sinai, New York City. He is a consultant for several pharmaceutical companies, including Aerie Pharmaceuticals, Allergan, Bausch + Lomb, and Novartis.

Articles

Our supply of dorzolamide, long a first-line glaucoma therapy used alone or in fixed combination with timolol, has recently proven unreliable.

Breaking down the dorzolamide shortage

,” a blog series featuring contributions from members of the ophthalmic community. These blogs are an opportunity for ophthalmic bloggers to engage with readers with about a topic that is top of mind, whether it is practice management, experiences with patients, the industry, medicine in general, or healthcare reform. The series continues with this blog by Nathan Radcliffe, MD and Sarah H. Van Tassel, MD. The views expressed in these blogs are those of their respective contributors and do not represent the views of 

The recent publication of findings from the 

 helped to confirm what many of us who treat glaucoma already suspected: 

 should be offered to patients diagnosed with 

LiGHT was a prospective, randomized, multicenter, observer-masked trial that enrolled treatment-naÃ¯ve patients with open-angle glaucoma or ocular hypertension for treatment with either

. The primary objective of the study was to assess quality of life outcomes after 36 months, with secondary objectives including cost and 

While there was no statistically significant difference in quality-of-life outcomes between the two groups, it is also evident that the best and most robust way to acquire this kind of data has not yet been identified.

Intuitively, it would stand to reason that quality of life is better in patients who are not on drops if they are not subjected to dry eye, redness, the burden of remembering to instill drops (potentially multiple times a day), and to stress and anxiety when drops are missed.

Overall, 95% and 93.1% of eyes in the SLT and eye drop groups, respectively, achieved their target pressure at 36 months, and 74.2% of eyes of patients in the SLT group were drop-free at that time point. As the authors noted, getting patients off drops for at least 3 years may be between 25% and 33% of remaining life expectancy for patients with open-angle glaucoma, reflecting a more substantial benefit than may be evident from a strict reading of the data.

(VIDEO) SLT is a cost-effective, first-line glaucoma approach

Consistent with prior studies, it is also interesting that fewer patients in the SLT group required 

 throughout the study compared to the eye drop group. It may be that drop therapy exacerbated inflammatory or other processes that accelerated cataract development. While correlation does not prove causation, the finding reaffirms that drop therapy is not completely benign.

The LiGHT data also suggested that laser was more effective in controlling glaucoma, as eyes of patients in the SLT group were within 

 at more visits (93%) than in the eye drop group (91.3%).

Additionally, zero patients in the SLT group and 11 patients in the eye drop group required glaucoma surgery, and more eyes in the eye drop group (n = 36) compared with the SLT group (n = 23) exhibited disease deterioration, which was defined as progression of glaucoma or conversion from ocular hypertension to glaucoma.

These findings leave open the possibility that SLT may be 

. Although not entirely proven, there is some suggestion that persistent but controlled flow of aqueous through the trabecular meshwork helps maintain outflow capacity-much like a muscle that needs to be exercised to maintain viability.

In this way, aqueous suppressants (and even prostaglandin analogues to a certain extent) may not be beneficial to the health of the trabecular meshwork, whereas SLT may offer an advantage in keeping the physiologic outflow system functioning for as well as it can for the long term.

Novel DSLT Taking Aim At Greater Access To Glaucoma Care

SLT is not new to the glaucoma space. It was invented by Mark Latina, MD in the 

 and brought to market by Lumenis shortly after. Lumenis technology, which was used in the LiGHT study, is what we use for our SLTs, and 

 continues to be a leader and innovator in this space.

SLT has emerged as a simpler, less confusing, and more efficient option for patients than medical therapy with comparable, if not better, clinical outcomes. As noted in LiGHT, SLT is likely more cost effective than eye drops.

We add to this an additional perspective-from a financial standpoint, prescribing drops entails expense for the practice (primarily in the form of resource allocation for pharmacy and patient call backs) whereas SLT can be a revenue-generating portion of the practice. In the near future, sustained-release therapies may become available as attractive non-drop options.

Patient acceptance is definitely the biggest barrier to wider use of SLT as first-line therapy. Each of us offers SLT as initial therapy for patients newly diagnosed with mild to moderate glaucoma, but we are careful to leave the final decision to the patient. Understandably, undergoing a procedure, even one as safe as SLT, can induce 

At the least, mentioning the possibility of laser at the onset plants an idea that can be revisited if medical therapy proves unsuccessful, intolerable, or too inconvenient.

Related to this, we avoid focusing too much on the 

 of drops when discussing treatment options, which might raise doubts in patients’ minds if they choose to go that route and encourage suboptimal compliance.

Overall, it is encouraging that the majority of patients in each group achieved their target pressure with low rates of progression.

However, as one digs deeper into the LiGHT study, a lot of the more subtle findings help highlight the benefits of using SLT as first-line therapy for patients, physicians, and payers.

MIGS Developments Continuing To Transform Glaucoma Surgery

Dr. Radcliffe is a consultant for Lumenis, Ellex, Iridex, and Beaver Visitec International.

Dr. Van Tassel has no financial disclosures.

1. Gazzard G, Konstantakopoulou E, Garway-Heath D, et al; LiGHT Trial Study Group. Selective laser trabeculoplasty versus eye drops for first-line treatment of ocular hypertension and glaucoma (LiGHT): a multicentre randomised controlled trial. 

2. Garg A, Vickerstaff V, Nathwani N, et al; LiGHT Trial Study Group. Primary Selective Laser Trabeculoplasty for Open Angle Glaucoma and Ocular Hypertension: Clinical Outcomes, Predictors of Success and Safety from the Laser in Glaucoma and Ocular Hypertension (LiGHT) Trial. 

3. L tina MA, Park C. Selective targeting of trabecular meshwork cells: in vitro studies of pulsed and CW laser interactions. 

Selective laser trabeculoplasty (SLT) should be offered to patients diagnosed with open-angle glaucoma as a first-line therapy.

Nathan Radcliffe, MD

Articles

Breaking down the dorzolamide shortage

Perspective: New data support first-line use of SLT for glaucoma