Tag: glaucoma

Glaucoma Management from the Anterior Segment

By: Paul M. Karpecki, OD, FAAO Clinical Director – PECAA

Co-morbidities are inevitable and we need to be consciously looking for them. The perfect example is glaucoma and ocular surface disease (OSD). As PECAA Members we have  to realize the ocular surface and dry eye in particular may be the number one financial drain to the profession, responsible for contact lens drop out, spectacle remakes, IOL miscalculations and now it also appears to be one of the top causes for lack of compliance to glaucoma medications.

Trust me, I know we get into silos when we categorize a patient. For example I consider myself a cornea/OSD doctor first, having completed a fellowship in cornea back in 1994. And yet when I see glaucoma patients, I tend to fixate on progression and my target IOP, often overlooking OSD. These are co-existing diseases that should not be missed because it could be that OSD the primary reasons glaucoma progresses. In fact, glaucoma patients who are on preserved (especially BAK) drops have a significant increase in the presence of ocular surface disease.1 One study showed that having a history of at least 3 years of glaucoma therapy increased the odds ratio of OSD by more than five times and if exposed to at least 2000 Mg of BAK it increased the odds ratio by more than 100 times.1 From a patient standpoint, BAK and prostaglandin analogs may result in pain upon instillation, eye redness, dry eye and blurred vision resulting in a tendency to stop using their glaucoma medications (until a week or a few days before their scheduled eye exam when they resume drops). I’m not joking about the patient resuming drops the week of their eye exam as studies have shown that patients do exactly that. In one published paper, patients over estimated their adherence to their glaucoma medications by 95%.2  This study showed that patient adherence peaked just prior to an appointment, and lapsed soon after the exam, confounding long-term intraocular pressure assessments.2 The result is an increase in IOP and we as doctors think the glaucoma medications need to be changed or another drop added. Adding another drop then makes the OSD worse!

It’s patient adherence and more specifically due to the ocular surface disease, that is the culprit for progression of glaucoma in many cases.  Research has shown that glaucoma patients who reported experiencing an ocular side effect had far more glaucoma disease progression in the first 2.5 years since diagnosis, as those who did not report experiencing ocular side effects (P<0.008). This translates to a relative risk of disease progression being 3.3x greater for patients reporting ocular side effects. And who is most likely to experience ocular side effects? According to a study involving more than 20,500 glaucoma patients, those with dry eye disease/OSD had 12 times the rate of symptoms such as foreign body sensation and ocular pain, and 4 times the rate of blurred vision and photophobia compared to patients without ocular surface disease.4 It seems obvious that a person with pain, FB sensation or blurred vision is likely to stop the drops that are causing these symptoms.

I know we are hesitant to add another medication to a glaucoma patient’s list for fear of confusion, improper dosing, reduced compliance etc. so now add OSD to the list of reasons. But we can’t risk glaucoma progressing, so be selective in what drops you use or consider different glaucoma medications and even surgeries like SLT or the Hydrus micostent. As far as managing the glaucoma, consider drops without preservatives (e.g. Zioptan, or Cosopt PF), or the next best option would be drops with non-BAK preservatives such as Xelprose or Travatan-Z. Consider using only a single agent that has the most IOP lowering effect such as Vyzulta or Rocklatan rather than adding another drop. Finally there is the option of preservative free compounded drops such as the Imprimis triple or quad drops. These compounded drops allow combinations of 2, 3 or even 4 glaucoma mediations making it easy for patients to adhere to therapy and are preservative-free. I have an advanced glaucoma patient that takes the quad drop at night and the triple drop in the morning and went from initial pressures in the 30’s to 9mmHg OD & OS.

A glaucoma patient on multiple topical medications with advanced dry eye disease

If the ocular surface disease is significant try to get the patients off of glaucoma medications completely with treatments such as SLT or a MIGS (micro-incisional glaucoma surgery) procedure such as the Ivantis Hydrus or iStent at the time of cataract surgery.

New research has shown that 3 years after a Hydrus micro-implant was inserted, over 80% of the patients who had previously been on a single glaucoma therapy, were completely medication-free. Find surgeons who are using the Hydrus Microstent specifically and take to time to meet him or her and begin co-managing you glaucoma patients with cataracts.

Finally consider treating the OSD. Frankly, artificial tears are usually not enough to help the OSD issue associated with glaucoma. So if you have to add a therapeutic to treat the inflammation caused by OSD consider preservative-free therapeutics such as lifitegrast (Xiidra) or cyclosporine (Restasis or Cequa).  Or consider treating the specific OSD with an in-office treatment. If it’s blepharitis/MGD think of blepharoexfoliation with a Blephex device and thermal pulsation (e.g. LipiFlow, iLux, TearCare or Thermal 1-Touch) or IPL (Lombart or Lumenis) followed by a daily hydrating compress (e.g. Bruder Medibeads). I recently purchased the EyeLight IPL distributed by Lombart and have  been impressed with the results, the decreased cost, the fact that it doesn’t require coupling gel and can treat almost any skin type.

It’s time to start looking at co-morbidities, such as OSD as the reason for failed success in glaucoma patients. Manage these co-morbidities and your success in glaucoma will rise significantly.

Summary:
1. Rossi GC1, Pasinetti GM, Scudeller L.  Risk factors to develop ocular surface disease in treated glaucoma or ocular hypertension patients.  Eur J Ophthalmol. 2013 May-Jun;23(3):296-302.
2. Reardon G1, Kotak S, Schwartz GF.   Objective assessment of compliance and persistence among patients treated for glaucoma and ocular hypertension: a systematic review.  Patient Prefer Adherence. 2011;5:441-63. doi:0.2147/PPA.S23780. Epub 2011 Sep 23.
3. Denis P., Lafuma A, Bordeaux G et al.  Adverse Effects, Adherence and Cost-Benefits in
Glaucoma Treatment.  European Ophthalmic Rev. 2011;5(2):116-122      
4. Erb C1, Gast U, Schremmer D.   German register for glaucoma patients with dry eye. I. Basic outcome with respect to dry eye. Graefes Arch Clin Exp Ophthalmol. 2008 Nov;246(11):1593-601.

What’s New in OSD & What We Need to Know: Part 2

By: Paul M. Karpecki, OD, FAAO Clinical Director – PECAA

This is a question I receive often and seemed like a good feature for the mid-year newsletters. As I started researching this question it quickly became evident that a lot has happened in the world of dry eye/ ocular surface disease in a short time. It was so extensive we had to divide it into two parts.

Kala KPI-121

This drug is 0.25% loteprednol for the treatment of dry eye disease (DED) flare ups. The drug is in phase III clinical trials for a potential approval in late 2019 or early 2020.  It will be interesting to see if we have a new drug with a treatment for a critical component of DED. What you need to know:

  • Dry eye is a chronic inflammatory disease with flares that are characterized by acute exacerbations of signs and/or symptoms
  • A dry eye flare is a rapid onset, inflammation-driven response to a variety of triggers that typically cannot be adequately managed with the patient’s ongoing therapy
  • Regardless of dry eye severity, flares typically occur 4-6 times per year
  • The concentration is 0.25% and the vehicle involves mucous penetrating particles (MPPs) which are nanoparticle in size (<500 nm) to achieve efficacy and tissue penetration through mucus pores

VitalTears

Having access to autologous serum eye drops (ASEDs) is essential in managing dry eye within a practice.  Up to now there has not been easy access and patients can’t ship their blood far for processing etc. A new company called VitalTears has an affordable and extremely patient friendly approach to providing this essential treatment option. What you need to know:

  • Autologous serum has the same components as our tears but typically in higher concentrations. 
    Recall that our accessory lacrimal glands essentially take the serum in the blood supply to create tears. Patients who cannot make their own tears (KCS, Sjogrens’  Syndrome KCS, neurotrophic  keratitis) rely on this product enters nothing that completely substitute for a patient’s tears compared to autologous serum

  • Conditions that typically require ASEDs include KCS, NK, limbal stem cell deficiency, chronic corneal staining,  persistent epithelial defects and even recurrent corneal erosion to name a few

  • VitalTears has a phlebotomist that arrives at the patient’s home or work and draws the blood and the center processes it based on the doctors prescription for the optimal concentration

  • Most patients do well on a 25% concentration although doctors can prescribe up to 100%. Almost all my patients are on 25% concentration although I’ve used 40% in very advanced diseases such as significant neuotrophic ulcers

Acthar

Acthar is an corticotropin IM or SC injection, which allows the body to provide its own adrenal glucocorticosteroid response. It stimulates the body’s anti-inflammatory responses for treatment of conditions such Sjogrens KCS or uveitis. You need to know:

  • Acthar is approved for the treatment of severe acute and chronic inflammatory disorders of the eye
  • Acthar r binds to melanocortin receptors and elicits both steroid-dependent and independent properties
  • It has decades of clinical experience across multiple disease states since approval for use more than 65 years ago and when you prescribe this, an at home healthcare provider can dose the patient at home or wherever is convenient for them
  • Usual dose is 40 to 80 units every 24 to 72 hour but dose and duration of therapy should be individualized for each patient
  • Patient training and support available through Mallinckrodt Pharmaceuticals

CEQUA

This newest form of cyclosporine was actually approved by the FDA late last year, because of manufacturing issues it has not been available, until now. What you need to know:

  • This drug class is known as calcineurin inhibitor immunosuppressants indicated for increased tear production in patients with KCS
  • Dosing is b.i.d. and the concentration is 0.09%
  • The formulation involves a nanomicelle, which has a hydrophobic core where the cyclosporine is housed surrounded by a hydrophilic outer layer that allows for greater ocular penetration
  • This hydrophilic outer layer is compatible with the aqueous layer of the tear film allowing for transport to the ocular surface, where the drug is then released
  • The drug showed a statistically significant improvement in Schirmer scores and total corneal staining compared to vehicle at day 84. The most common adverse event was installation site pain in about 24% of patients

Oasis Tears and Oasis Tears Plus

New research reports1 have recently come out showing the incredible benefit of hyaluronic acid (HA) based drops. You need to know:

  • The highest concentration of HA currently available in a drop is Oasis Tears Plus, but HA is also found in Bio True contact lens solutions and artificial tears such as Blink
  • An interesting paper was recently published comparing cyclosporine eyedrops to drops containing HA
  • Administration of 0.1%, 0.15%, and 0.3% HA was effective in improving both the objective signs and subjective symptoms of dry eye. Those findings, in addition to the well-tolerated profile, show that it is an effective therapeutic option for dry eye
  • The results concluded noninferiority and in some cases better results

OcuSoft Lid Scrub Allergy Eyelid Cleanser

OcuSoft has long been a trusted and effective hygiene company with the largest market share of lid scrubs and hygiene cleansers. This month they introduced a novel allergy eyelid cleanser.  What you need to know:

  • It comes in premoistened pads
  • In addition to removing pollen, debris, allergens, oils and contaminants it also treats the itching, inflammation and redness
  • Inflammation is targeted via ingredients such as green tea extract, itching via tea tree oil and redness with PSG–2 (phytosphingosine) an ingredient used for redness in current rosacea treatments
Meibography of a healthy patient

 

Meibography of a patient with advanced dry eye and rosacea

Oculus Keratograph M5

Oculus has come out with a new approach to making one of the very best dry eye diagnostic technologies available to clinicians. What you need to know:

  • The technology is priced where other meibographer reside but has added technologies. For
    example you can get Oculus meibography with non-invasive tear break up time and tear meniscus height measurements in a single unit
  • Topography is available in a higher priced model and other dry eye features
  • There are three technology options and you can customize reports as needed to come up with your final Keratograph M5 package
  • This is truly one of the best systems for dry eye diagnosis and technically provides almost everything the TFOS DEWS II diagnostic committee recommends in one technology
  • The world of ocular surface disease continues to expand and advance.  These are indeed terrific opportunities for our practices and our patients.
Summary:
1.  Park Y. Et al. A Randomized Multicenter Study Comparing 0.1%, 0.15%,  and 0.3% Sodium Hyaluronate with 0.05% Cyclosporine in the Treatment of Dry Eye.  Journal of ocular pharmacology and therapeutics. 33(2):66-72

What’s New in OSD in 2019 & What We Need to Know

By: Paul M. Karpecki, OD, FAAO Clinical Director – PECAA

This is a question I receive often and seemed like a good feature for the mid-year newsletter.  As I started researching this question I became amazed at what all has happened in dry eye disease in such a short time.

A New Therapeutic for Neurotrophic Keratitis

Oxervate (Cenegermin) is an endogenous human nerve growth factor that was approved by the FDA for the treatment of neurotrophic keratitis (NK).  What you need to know:

  • The dosing is Q2H or 6 times per day for 8 weeks
  • It is essentially a cure rather than a treatment.  Meaning 80% of the patients treated for 2 months that had complete corneal staining resolution maintained it one year later
  • It’s prescribed via Rx and usually requires the patient to submit an additional form to the company (Dompe) to aid in patient assistance programs, help with prior authorizations etc. should patients not be able to afford it
  • The drops are delivered to the patient’s home frozen and the company assists in how to create daily vials etc.
  • Efficacy begins as early as week 4 and 72% of patients had complete resolution or corneal staining and lesions by week 8
  • No systemic risk was noted
  • The only other product that has research to show it can improve nerve function is the cryopreserved amniotic membrane known as ProKera

In Office Procedures Advance

As reimbursements decline and vision plans continue to try to balance patient costs with quality
optometric care (two factors that can be at opposite ends of the spectrum), optometry finds itself in need of new opportunities. One such opportunity is that of in-office patient patient treatments. What you need to know:

  • Insurance does not yet cover these procedures and doctors are able to price them in ways that allow many patients to receive the benefits but also fair to the financial health of a practice.
  • One essential in-office treatment is that of Blephex. Removing the biofilm from the lashes and eyelid margins of patients with MGD/blepharitis has shown a significant improvement in signs and symptoms for patients.
  • I’ve had patients state that their eyes have not felt this good in decades.
  • Another critical in-office procedure is that of thermal pulsation such as LipiFlow (J&J Vision), which was the first advanced technology in this space and is highly effective.
  • One treatment of LipiFlow typically lasts 2-3 years.
  • A recent study showed that a single LipiFlow treatment, in patients with contact lens discomfort, increased wearing time by 4 hours per day.1
  • The cost of a LipiFlow activator has decreased from $350 to $100 this year.
  • Other options for thermal MGD therapy to have recently joined include iLux, TearCare and on June 26th OCuSOFT announced the purchase of Digital Heat’s Eyelid Warming Device.
  • iLux (Alcon) is a hand held device that also heats the back surface of the eyelids and provides the ability to view the expression of meibum.
  • It had impressive improvements in OSDI symptoms scores, TFBUT and meibomian gland expression scores at 2 and 4 weeks after treatment.
  • TearCare (Sight Sciences) provides and on-eye lid, open eye, blink regulated, natural approach to expressing glands.
  • The TearCare hub monitors the temperature over 240 times per second and the treatment lasts 15 minutes.
  • OcuSoft’s Digital Heat Device is likely to be the least expensive option for in-office treatments and involves a device that heats the outside of the eyelid for approximately 10 minutes

Eye-Light IPL

A new IPL was introduced in 2019 from Lombart called the Eye-Light. It has signifiant advantages from any other previous IPL technology.

  • It does not require coupling gel to transmit the effects. Coupling gel was something that patients did not like having on their face.
  • It is a painless patient experience based on a two part IPL treatment.
  • It can treat any skin type or color,  which was not possible prior to this technology.
  • Patients typically require only 2 (sometimes 3) treatments about 3 weeks apart, which is less than in the past.
  • It works! In my first 50 patients I can see a significant improvement in telangiectatic vessels and overall inflammation in the eye. Patients have had noticeable improvements in symptoms.
  • The cost is significantly lower for the equipment and for the cartridges to treat patients.
  • IPL can be combined with the above treatment options like Blephex and thermal pulsation.

Hypochlorous Acid (HOCI)

In about 6 months there have been six new entrants to the HOCl market. What you need to know:

  • Hypochlorous acid, also known as HOCl, has the same active ingredient of household bleach but has a different chemical structure and significantly lower concentrations.
  • Pure HOC1 is produced naturally as an element of the human immune response, specifically released by neutrophils
  • Preservation is an important consideration since the stability of hypochlorous acid solution is generally quite limited. To clarify, although the shelf life of hypochlorous acid may be years in some cases, once a bottle of hypochlorous acid is opened, the product becomes less stable and it begins to degrade  typically lasting only 1-2 months.
  • The newer forms like Zenoptiq (Focus Labs) or SteriLid Antimicrobial (Akorn) have shelf-lives, once opened, that exceed 18 months.
  • HOCl has been shown to be effective against bacteria, viruses such as EKC and fungi (but not demodex)

Lotemax SM (B+L)

SM stands for small molecule and this new formulation of loteprednol from B+L has impressive properties. For one, it defies optometry board questions as a lower concentration of drug (0.38%) results in a higher potency, corneal and aqueous humor concentration. What you need to know:

  • It’s the same ester-based steroid but with a particle size that is 5-10 times smaller allowing for
    greater surface area coverage and more penetration of the drug thus allowing the lower
    concentration (0.38% compared to 0.50%) with the much higher potency.

  • Most pharmacies honor this Lotemax since it has the same name and the Walgreens and
    independent pharmacy forms from B+L allow Lotemax SM to be $25 for all patients under age 65 and $60 for patients with Medicare.

Eveleve (Bruder Healthcare) 

From the makers of Bruder mask comes a hydrating, anti-bacterial compress that showed more than a 3 hour increase in comfortable contact lens wearing time based on a study from  the University of Alabama at Birmingham School of Optometry.  What you need to know:

  • The compress maintains optimal temperature of 104-114 degrees for up to 10 minutes after 20 seconds in the microwave.
  • It has an antibacterial back surface material designed to reduce  bacterial flora to normal levels with each wear.
  • It has clinical proof of a significant improvement in contact lens wearing time in patients who were beginning to notice decreased wearing time.
  • The study showed that use of the mask compared to the bundled method was statistically better  at once a day and only marginally better with twice a day use, so once a day use for 10 minutes is sufficient to achieve these results.
  • It contains silver ions around the Medibeads for further antibacterial moisture release.

Flarex (Eyevance Pharmaceuticals) 

This fluoromethalone acetate steroid was recently launched and has properties no other steroid appears to have. What you need to know:

  • If you see a patient with conjunctival staining, filamentary keratitis or mucous strands in their
    tearfilm etc. consider Flarex as the drug of choice for 4-6 weeks (monitoring IOP).
  • The reason is that Flarex has been shown to positively modulate gene expression of ocular surface mucins.2
  • The ocular surface expresses 3 membrane-bound mucins; MUC1, MUC4, MUC16 and all are affected in patients experiencing the above issues and can be improved with Flarex.
  • The same occurs for secreted mucins (MUC 19).
  • This may be our best  approach to patients with goblet cell or mucin deficient issues.

The world of ocular surface disease continues to expand and advance. These are indeed terrific
opportunities for our practices and our patients.

Summary:
1.  Blackie, CA, et al. A single vectored thermal pulsation treatment for meibomian gland dysfunction increases mean comfortable contact lens wearing time by approximately 4 hours per day. Clin Ophthalmol, 2018; 12:169-183.
2. Taniguchi J., Sharma A.. Fluorometholone modulates gene expression of ocular surface mucins. Acta Ophth 1-7:2019.

Dry Eye Updates

By: Paul M. Karpecki, OD, FAAO Clinical Director – PECAA

I first have to apologize I wasn’t able to participate at PECAA’s Annual Meeting this past month. It’s the first time since I began my role as clinical director at PECAA that I’ve not been present.  I heard it was a great conference once again, but I also received an exorbitant number of emails and calls from my PECAA colleagues regarding dry eye. So let me answer some of those questions I received as this month’s column.

Is osmolarity truly of no value?

This was the most common question I received so I’ll address it first. I think whoever was the speaker on dry eye disease probably didn’t say that osmolarity was of no value as it is a 5 second test that has the highest predictive value in diagnosing dry eye of any test available. It was listed as one of the essential tests in the ASCRS Preferred Practice Guidelines that was published this past month, as well as TFOS DEWS II global test recommendations in the diagnostic methadology section. I personally couldn’t imagine running a dry eye clinic without osmolarity testing anymore than I could manage glaucoma without OCT. But I believe the speaker was simply saying that you can still manage dry eye without it (just as you can manage glaucoma without OCT but not as effectively). I also feel that unless dry eye is a major focus of your practice and you have the ability to dedicate one tech who gets very good at osmolarity testing, you should begin with other testing such as vital dyes and tear film breakup measurements. Finally I believe that regardless of what equipment or diagnostic tests we have ranging from meibography to tear meniscus height assessment and MG expression, we have an obligation to take care of this enormous patient population. So basically work with what you have and this part of your practice will evolve to where osmolarity testing makes sense.

Does hypochloorus (HOCl) acid kill demodex?

The only study I could find on this was actually a poster by Alan Kabat OD, that compared high concentration tea tree oil to HOCl to mineral oil (as the control). In this study he basically plucked demodex parasites off lashes and placed them under a microscope slide in one of 3 solution as outlined previously. The results showed that after 3 hours all of the demodex combined with 50% tea tree oil were killed but almost none of those in HOCl were affected any more than the control group in mineral oil.

Others have stated that HOCl kills the the food supply and indirectly kills demodex. It’s unlikely as demodex is a scavenger that survives on a lot more than bacteria and quite frankly, even though I like HOCl as a treatment, it doesn’t eradicate all bacteria including our natural fluora (fortuantely). Demodex also eats meibum, hardened oils, keratin, blood and anything else it can scavenge. That being said, HOCl acid is an effective antimicrobial for bacteria and possibly even for adenovirus. It is relatively natural as our white blood cells essentially produce HOCl and it’s very effective. I like using it in moderate to advanced cases of staphylococcal or bacterial blepharitis, then moving back to surfactant cleaners at times. If there is an issue with HOCl acid solutions it is that once opened many of them become nothing more than saline (as the pH drops) within 1-2 months. For that reason I prefer brands that are stable after opening for 18-24 months such as Zenoptiq (Focus Labs) or SteriLid Antimicrobial. Zenoptiq is in a blue bottle and is stable for over 18 months even after opening and comes in both a spray and a gel.

So what is the best treatment for demodex?

Currently there are only two options as Cliradex is not available (although it could be available again once this paper is published). These are blepharoexfolioation or mechanical cleaning with low dose tea tree products– and the most effective approach I have seen is with Blephex. This debulks and mechanically removes the pathogens. It’s important to wait 10 minutes between treatments as it seems like during that time the demodex come to the surface and that second treatment has a greater effect.  The other is the Oust Swabstix from OcuSoft with higher concentrations of tea tree and sea buckhorn oil. My preference from a comfort perspective is Blephex but these are the two treatments I’ve seen be most effective for demodex. Don’t forget to include daily at home maintenance after these in-office treatments. Maintenance is best achieved with a low concentration tear free product such as Oust in the canister with tea tree, Cliradex light, SteriLid and my personal preference, Oasis Lid and Lash with Tea Tree.

The DREAM study states that there was no difference between fish oil and placebo in the management  of dry eye, does that mean we shouldn’t recommend it anymore?

It is true the DREAM study showed no statistical difference between a high grade triglyceride form of fish oil and refined olive oil (as the placebo) in a large scale, multisite study. The fact is that the fish oil had a highly statistical improvement in dry eye signs and symptoms, it’s just that the placebo did as well.  I think the reason for this is the study involved far too many variables as it was deemed a ‘real world’ study meaning patients could maintain treatment with other products ranging from lid scrubs to Xiidra.  Also olive oil, even though refined to remove anti-inflammatory properties, may not have been the best placebo choice. But I think the DREAM study shows me that pure fish oil, although effective, may not be enough and combination products such as HydroEye (combines fish oil with GLA from black currant seed oil) may be more effective as I’ve seen in my own clinic.

Has the use of thermal pulsation like LipiFlow decreased the need for other DED treatments like Restasis or Xiidra?

The answer is yes in some cases but no in the majority of cases. Let me explain because it has to do with what stage of disease you diagnose. Like any disease process, the sooner we treat the patient the better. So if a person is pre-dry eye such as having early meibomian gland dysfunction, a thermal pulsation treatment alone may be sufficient. However most patients only seek treatment or most doctors only diagnose the disease when it is moderate or advanced. At this point there are four elements to most cases of evaporative DED and that includes obstruction of the meibomian glands, biofilm or blepharitis, inflammation and tear film instability. So treating just one element (even as good as LipiFlow may be) is usually insufficient at this stage of the disease. And like blepharitis, maintenance with options such as a Bruder mask, are imperative just as brushing and flossing one’s teeth still occurs after the dental cleaning. Here are options in each category that may work most effectively and be sure to select at least one treatment from each category to achieve success. Keep in mind that aqueous deficient dry eye has a different protocol but over 80% of all dry eye involves an evaporative component so this chart provided may help most dry eye.

When It Comes to Glaucoma, You’re In Charge

By: Paul M. Karpecki, OD, FAAO Clinical Director – PECAA

Glaucoma is something optometry has to go into with the attitude of taking charge. As a profession we see 88% of all comprehensive ocular examinations in the U.S. and are likely to diagnose as many as 8 out of 10 cases of glaucoma. Immediately referring these patients out emphasizes how we don’t manage medical eye care and that’s just not right. Certainly there will be cases that require referral but most early and primary glaucoma cases are ours to manage. Given the shortage of ophthalmologists, the aging population and the number of cataract patients ophthalmology will have to operate on, there is no way for the eye care system to work efficiently if we’re not quarterbacking patients with glaucoma. 

Obligation and Practice Protection

Another reason to be proactive about glaucoma besides it’s an obligation as an eye care practitioner, is to protect yourself and your practice. The number one reason for malpractice cases against an optometrist is failure to diagnose glaucoma (and I’ve served as an expert witness for at least four such cases). No one wins meaning, meaning even if the case doesn’t find the optometrist culpable, the patient is still often visually affected, and the time and consequences of going through the process are hard on everyone. So let’s look at what’s new in glaucoma.

ORA and OFA

Two similar acronyms for two new diagnostic tools. The Ocular Response Analyzer (ORA) from Reichert, measures hysteresis (and more), which is a critical measurement for glaucoma management. In cases that seem on the fence as to starting treatment, it is the ORA that makes the decision for me. There are four key measurements involved:  The waveform score, which is a measure of reliability is the first thing to look at to ensure the measurement is accurate. Next is hysteresis, which is the ability of the cornea to absorb pressure like a shock absorber. In fact it is the most predictive measurement of
worsening glaucoma or loss of visual field. A reading of less than 8 indicates a patient that is most likely to be a fast progressing case. IOPg gives the Goldman correlated IOP and is very accurate and IOPcc measures the corneal compensated IOP.  I’ve seen patients with thin corneas (505 microns) have an IOP of 16 with Goldman but 19 with IOPcc and that explained why they were progressing. Corneal thickness has been proven to be inaccurate in predicting actual IOP. The ORA is extremely valuable in determining a suspect versus one with glaucoma and it’s a new technology NCT, which is not at all like the NCTs of the past.

The ObjectFIELD Analyzer (OFA) is the newest device to be approved (Konan Medical) and is a revolutionary innovation. If you were to ask patients what test they dislike the most in an optometry or ophthalmology office, they will often say visual field testing.   And it’s extremely frustrating for the doctor too! We’ve all had the patient who after 20 or 30 minutes of testing had so many errors that the data was worthless and it had to be repeated. Current subjective visual field testing is not reliable and often takes multiple attempts. I’ve seen cases that looked alarming that were completely normal after the subjective third visual field test and I’ve had patients that fell asleep while taking the test! It’s time for something new and accurate. This is the first objective field analyzer. It takes less than 7 minutes to run a 30-2 (and it give you the 24-2 information as well). You can also run macular field testing so it’s versatile. The device documents the reaction of the pupil to stimulus in each of the hemifields and works in patients who have had a stroke to neurological disorders to glaucoma. Even the color of the test object neutralizes brunescence and thus cataracts will not affect testing. It bases measurements on amplitude and latency of the pupil response to a specific stimuli and in less than 7 minutes provides a printout similar to the visual fields we are accustomed to interpreting. In fact the inventor, Ted Maddess PhD, also invented subjective perimeter testing. I believe that objective field testing may one day replace the frustrating subjective field testing, which looking back will seem archaic.

A Third New Therapy just Approved

It’s been over 20 years since we’ve had any fundamentally new topical drugs for glaucoma and as of last month we’ve had three in about a year! The most recent approval is that of Rocklatan (Aerie Pharmaceuticals). Rocklatan is a combination of Rhopressa with latanoprost. Now before you say that’s not new as Rhopressa or netarsudil was approved last year and latanoprost over 20 years ago, the fact is that the reason we’ve not seen a combination agent approved in decades is because the FDA now requires that the combination be superior to each independent drug combined. Meaning the combo must be better than Rhopressa’s effect alone + latanoprost effect alone. What that meant to me was that we’ll likely not see another combination agent…. well until last month. Rocklatan, dosed QHS, showed IOP lowering effects that were greater than any other FDA clinical trial with almost 80% of patients achieving an IOP less than 18mmHg and 41% with IOP’s less than 14mmHg. Netarsudil, alone as in Rhopressa or within Rocklatan is an entirely new class of glaucoma medications known as RhoKinase inhibitors which target or possibly remodel the TM.

The other advanced glaucoma drug involves the use of nitric oxide (NO) and that is Vyzulta (lat-anoprostene bunod 0.024%, Bausch Healthcare). What makes both of these drugs unique is that they work on the trabecular meshwork. Vyzulta, which is dosed QHS also, utilizes a PA but also butanediol mononitrate, which releases NO. NO has been shown to relax the TM to increase outflow.1 In glaucoma patients the TM is often compacted, which thus prevents proper aqueous outflow. Studies have shown that patients with glaucoma have a lower concentration of NO in their eyes due to high concentrations of NO synthase.2 My own experience shows Zyvulta to be a superior glaucoma medication in reducing IOP as a first line therapy and clinical studies showed it lowered IOP more than any previous glaucoma medication when compared to timolol BID. So we have two drugs that finally target where we have the disease – the TM.

MIGS

For the most part, the one chance we have at recommending a microincisional glaucoma surgery (MIGS) is at the time of cataract surgery. The procedures are very effective and have minimal complications.3 Most patients are down to 1 or no medications after implantation.4 There are over 4 million cataract procedures performed per year and approximately 20% of the cataract population has concurrent glaucoma. This is a terrific opportunity to add a MIGS. Ab interno procedures (internal outflow essentially) are showing great promise and the newest approved MIGS device called the Ivantis’ Hydrus Microstent have shown a 43% greater IOP lowering than cataract surgery alone. Furthermore the IOP delta compared to the group not receiving a MIGS was lower in year two compared to year one. These results exceed any previous pivotal trial for a MIGS technology. Optometry’s recommendation goes far and provides them the opportunity to go to 1 or no medications. And just because they have a MIGS doesn’t mean their glaucoma is cured; it still requires a typical follow-up and appropriate testing of 3-4 visits per year regardless of if they are on topical medications or not, to monitor for disease progression.    

The Role of Compounding in Glaucoma Management

I recently had a family friend’s grandfather present with 0.9 CDs, visual field loss and pressures of 27 and 28 on 3 different glaucoma medications. Perhaps there was some non-compliance but he was on track to complete vision loss. I performed an SLT, which initially lowered his pressures to 19 OU. I was pleased with his outcome but six month’s later his pressures were consistently 22 and 23. He needed cataract surgery so a MIGS was performed lowering him to 18 in each eye. Given his fixation loss potential and gauging his difficulty with various drops at various times, I resorted to the Imprimis Quad Drop QHS (Timolol, brimonidine, dorzolamide and latanoprost) PF and Triple (Timolol, brimonidine and dorzolamide) PF in the morning.  It’s been over two years now and his most recent visit is showing great stability in the disease and pressures of 13 and 12 consistently. I’ve been going to the compounding option sooner now in many patients who are having difficulty with multiple drops and/or need a preservative-free
formulation.

The incidence of glaucoma is increasing and it’s going to require optometry to play a very proactive role in order to manage this disease effectively by knowing about the newest medications, surgical options and new diagnostic technologies.

References:
1. Kaufman PL. Latanoprostene bunod ophthalmic solution 0.024% for IOP lowering in glaucoma and ocular hypertension. Expert Opin Pharmacother. 2017 Mar;18(4):433-44.
2. Neufeld AH, Hernandez RM, Gonzalez M.  Nitric Oxide Synthase in the Human Glaucomatous Optic Nerve Head.  Arch Ophthalmol. 1997;115(4):497-503.
3. Lee JH, Amoozgar B, Han Y.  Minimally Invasive Modalities for Treatment of Glaucoma: An Update.  Journal of Clinical & Experimental Ophthalmology.  2017, 8:4
4. Lavia C, Dallorto L, Maule M et al.  Minimally-invasive glaucoma surgeries (MIGS) for open angle glaucoma: A systematic review and meta-analysis PLoS One. 2017; 12(8): e0183142.
5. https://www.statista.com/statistics/302482/wearable-device-market-value/
6. De Moraes CG, Mansouri K, Liebmann JM et al.   Association Between 24-Hour Intraocular Pressure Monitored With Contact Lens Sensor and Visual Field Progression in Older Adults With Glaucoma.  JAMA Ophthalmol. Published online May 24, 2018.

Picturing the Future of Glaucoma

Picturing the Future of Glaucoma

By: Paul M. Karpecki, OD, FAAO
Clinical Director – PECAA

I’ve received numerous requests to discuss future technologies that PECAA Members need to be aware of. This seems like a good time to focus on glaucoma and each month we’ll try to cover a disease focus.

There is no question that optometry has to take a lead role in the management of patients with glaucoma simply because the profession sees 85% of all exams and is most likely to make the original diagnosis, manage treatment including laser procedures, referral for surgery and patient compliance. I think there are five things that will assist and/or help sort out the future of glaucoma:

1. Better diagnostics. There is no question that OCT has changed our ability to manage glaucoma. It allowed us to treat proper patients meaning a better diagnosis of glaucoma, it allowed us to begin treatment earlier to prevent blindness and it allowed the profession to manage these patients at an equal level to other eye care practitioners. However diagnostics must advance given the fact that we are all getting busier. In this fast-paced future of eye care, doctors need to understand what they are looking at, but also need to know when green means go, yellow for caution or red for stop. In other words, as companies bring in more complex diagnostic technology they also have to make it simpler to use. Corneal hysteresis has been shown to be the most predictive measurement of visual field loss progression and plays a key role in deciding to treat and even what we might expect a glaucoma therapy to do. Finally we have 24 hour home monitoring of IOP with technologies like iCare HOME. And even a hand help ERG that can measure for decreased conductivity.

2. MIGS and other non-invasive procedures. The introduction of the iStent in June 2012 has forever changed glaucoma treatment. Today and in the near future we have multiple MIGS technologies including Cypass, Xen, ABiC, KDB, ECP, iDose and iStent Supra. Just looking at the sheer number of options almost ensures growth in these procedures, but the primary reasons we as optometry need to know these is to help manage patient compliance, have options for those on maximum therapy, have glaucoma and cataracts and to replace invasive surgeries like a trabeculectomy. I believe the future will be a greater combination of laser procedures like SLT and especially MIGS, in addition to therapeutic treatment.

3. Better understanding of the disease. The fact is we don’t fully understand what causes glaucoma. We know that IOP is a risk factor and we know of other risk factors like corneal thickness, hysteresis, family history, age, race, high myopia, systemic conditions like diabetes, previous trauma, chronic inflammation etc., but we don’t truly know the cause. Is it blood flow or is there some other cause for neurodegeneration, metallic changes or neuropathy? Knowing the cause will allow us to treat the disease more effectively. The theory proposed by John Berdahl, MD suggests that it may be caused by an imbalance between IOP inside the eye and cerebral spinal fluid pressure (or Intracranial pressure—ICP) around the optic nerve affecting the metabolic needs. This can be supported by the fact that patients with idiopathic intracranial hypertension get a bowing of their optic nerve and 50% of astronauts develop vision loss because their CSF increases disproportionately higher than the IOP resulting in a hyperopic shift and optic nerve edema. So the key ratio may be IOP minus ICP as opposed to simply an elevated IOP. They have developed a set of nighttime goggles and a pump that in early clinical trials has been shown to decrease IOP substantially and prevent glaucoma progression. This could be an ideal treatment for Normal Tension Glaucoma if testing pans out.

4. New therapeutics and drug delivery devices. It’s been 2 decades since we’ve had a new glaucoma drug but that could change in the next 3-6 months. B+L’s Vyzulta (latanoprostene bunod ophthalmic solution) 0.024% is a nitric oxide-donating prostaglandin F2-alpha analog that in a recent study was shown to lower IOP by 9mmHg compared to timolol at 7mmHg.(1) Keep in mind that few if any previous glaucoma medications showed superiority to timolol in FDA trials. Perhaps it is the dual mechanism of action affecting both uveoscleral outflow and trabecular outflow of this drug that make the difference.(2) Nitric oxide (NO) is an important mediator with important effects on the vascular system and as a mediator of smooth muscle relaxation (and vasodilatation) including in the trabecular meshwork and in regulation of Schlemm’s canal. Studies show that glaucomatous eyes have lower levels of NO activity in the trabecular meshwork. A new drug class, RhoKinase inhibitors, may also change the landscape of glaucoma management because of their efficacy in IOP lowering but also, in the case of Rhopressa (netrarsudil), as a different mechanism of action. The second drug from Aerie pharmaceuticals with significant IOP lowering is Roclatan (netarsudil + latanoprost). Very recently the phase III data for Roclatan was released and IOP-lowering effect was 1-3 mmHg greater than monotherapy with either of its two components throughout the duration of the study. Knowing that adherence to medications is a major issue with non-symptomatic conditions like glaucoma, it is inevitable that new drug delivery systems will need to be utilized. Exciting developments in phase III clinical trials include Ocular Therapeutix travoprost eluding punctal plug technology that may last 3 months with each plug.

5. Treating the ocular surface. Another way to enhance adherence is to remember to manage the ocular surface. Patients with staining, blurred vision and irritation/dryness from drops like prosta-glandin antagonists or preservatives in glaucoma medications can cause patients to decrease or even discontinue use. Something as simple as managing the ocular surface may increase compliance and overall patient comfort.

Glaucoma is a key disease for optometry and these five elements may well dictate the future of disease management, our understanding and innovations in patient care.

Summary:

Special recognition to Review of Optometry, Author Paul M. Karpecki, OD, FAAO

1. Weinreb RN, Scassellati Sforzolini B et al. Latanoprostene Bunod 0.024% versus Timolol Male-ate 0.5% in Subjects with Open-Angle Glaucoma or Ocular Hypertension: The APOLLO Study. Ophthalmology. 2016 May;123(5):965-73.

2. Hedman K, Alm A. A pooled-data analysis of three randomized, double-masked, six-month clini-cal studies comparing the intraocular pressure reducing effect of latanoprost and timolol. Eur J Ophthalmol. 2000;10(2):95-104.

Don’t Overlook The Secondary Glaucomas

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Don’t Overlook The Secondary Glaucomas

By: Paul M. Karpecki, OD, FAAO
Clinical Director – PECAA

In these PECAA clinical pearls we sometimes feature new technology and other times clinical insights and even cases to help you protect yourself from malpractice by learning from others. Failure to diagnose is one of the most common reasons that patients file malpractice cases against optometrists. And, without question, glaucoma is the most frequently missed diagnosis I’ve observed as an expert witness.Although this secondary form of glaucoma known as pseudoexfoliative glaucoma or PXG, usually presents with advanced vision loss on initial examination in patient over the age of 60, it may present as pseudoexfoliation syndrome (PXF) in most of our offices. The time to make the diagnosis is when it is pseudoexfoliative syndrome (PXF) and monitor for the potential of glaucomatous changes regularly.
Once PXF present it can cause the IOP to elevate dramatically and rapidly progress to glaucoma (PXG). PXG has faster rates of progression to visual field loss, is less responsive to therapeutics and typically requires surgical intervention.1
unknownThe initial presentation of PXF is a whitish protein that deposits on the anterior capsule of the crystalline lens (and since it’s a systemic condition deposits on other tissues in the body). Interestingly it is also been associated with a higher incidence of hearing loss and Alzheimer’s Disease.2,3 It can also deposit on the endothelium which can be observed via specular microscopy. But the key observation is that of the anterior lens capsule where it looks like grayish-white flakey material, rolled edges and most often located in the periphery of the lens or pupillary margin area.
So is you happen to make a diagnosis of PXF, usually observed when performing a dilated pupil examination, you should immediately work up the patient for glaucoma and of course pay strict attention to IOP, which can elevate rapidly. Patients with this diagnosis should be seen at least every 6 months (or sooner if early signs of potential glaucoma may be present). Ultimately about 50% of patients with PXF go on to develop PXG likely due to the material depositing in the trabecular meshwork and obstructing aqueous outflow.
As with other secondary glaucoma forms the time intervals are much shorter to progression and prognosis is worse than that of primary open angle glaucoma.
A second case involved a young (mid 30s on initial visit), moderately myopic male patient, who was examined by various doctors in a group practice of optometry. In his 5 visits over 7 years, IOP was measured three times and omitted twice. The original IOP measurement on his first visit was 18 mmHg OD and 19 mmHgOS. The second visit had no IOP noted and same for the third. The fourth visit measured 23 and 26 without examining the optic nerve and the fifth visit, which resulted in a referral to a glaucoma specialist, was 26 OD and 38 OS. Optic nerve evaluation and fundoscopy was performed on the first visit noting optic nerve asymmetry and CD’s of 0.3 and 0.4. Seven years later, the optic nerves were 0.6 OD and 0.9 OS. The glaucoma consult confirmed glaucoma OU but advanced glaucoma OS. Was there something that could have been identified sooner to determine why this patient may have had escalating pressures?
The final diagnosis was pigmentary glaucoma, and so many times these uncontrollable glaucoma cases are in the class of secondary glaucomas. In this case the key was to observe the signs of pigment dispersion syndrome (PDS) before it became pigmentary glaucoma. Signs of PDS include a vertical line of pigment on the central corneal endothelium known as Krukenberg spindles, iris transillunination and pigment in the trabecular meshwork (TM) on gonioscopy examination. There is also a fourth sign known as Scheie line where pigment deposits along the peripheral posterior lens capsule – this would only be observed through pupil dilation. These findings tend to be bilateral and most commonly affect younger to middle aged men.
The theory of why this type of glaucoma can become extreme in terms of elevated IOP and non-response or loss of response to medications in patients who have had PDS for a long time, is likely due to scarring of the TM. This leads to a collapse of the intra- trabecular spaces and blockage of aqueous outflow.
It is important for clinicians to look for the signs of PDS, to understand the risks of developing pigmentary glaucoma and to monitor IOP and optic nerve findings on a regular basis.
Understanding the secondary glaucomas is very important since these can progress much faster than primary open angle glaucoma. Look for key signs while these conditions are syndromes and monitor them to prevent progression to glaucoma.REF: 1. Miglior S, Bertuzzi F, Exfoliative glaucoma: new evidence in the pathogenesis and treatment. Prog Brain Res. 2015;221:233-41.
2. J. B. RoedlS. BleichU. Reulbach et al. Vitamin deficiency and hyperhomocysteinemia in pseudoexfoliation glaucoma Journal of Neural Transmission. May 2007, Volume 114, Issue 5, pp 571–575
3. Samarai V, Samarei R, Haghighi N, et al. Sensory-neural hearing loss in pseudoexfoliation syndrome. Int J Ophthalmol. 2012;5(3):393-6.

 

Glaucoma Medication Side Effects & Contraindications

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Glaucoma Medication Side Effects & Contraindications

By: Paul M. Karpecki, OD, FAAO
Clinical Director – PECAA
Glaucoma affects millions of patients and is a very important part of optometry practice. We know there are inherent risks with almost all pharmaceutical agents and glaucoma medications are no exception. Having been an expert witness in a number of malpractice cases and most recently one involving glaucoma medications, makes me realize that a quick reminder of these contraindications (and side effects) is valuable.

Prostaglandin Analogs:

There are no absolute contraindications for this class except patients with a known hypersensitivity to the ingredients. However a relative contraindication would include patients with ocular inflammatory conditions such as uveitis, CME or chronic inflammatory eye disease. Another might be unilateral treatment because of the ocular side effects and there are times when unilateral glaucoma may develop such as in the cause of trauma with iris recession or post HZO or HSV uveitis. Ocular side effects include iris and sometimes periorbital skin pigmentation changes, eyelash growth, hyperemia, and orbital fat loss. Some patients may also experience burning and stinging with these drops.

UnknownBeta Blockers:

Contraindications to this class are generally patients with pulmonary or heart disease. This class of drugs can cause bradycardia or a lowered heart rate, lower blood pressure and can induce arrhythmia in susceptible patients. There are even reports that beta-blockers can raise serum triglyceride levels. They can also cause bronchial constriction, adversely affecting patients with asthma or COPD for example. They can cause sexual dysfunction, reduced libido, general weakness, depression and other central nervous system (CNS) side effects as well. Because the use of beta blockers has increased as a second choice medication mainly via combination agents, we must educate patients about these side effects.

Selective Alpha Agonists:

Although this class is generally well tolerated, there is a high incidence of allergy to certain brands within the class and many experts advise against the use of this class in children because of the potential CNS side effects. By stimulating alpha-2 receptors of the CNS, there is the potential for orthostatic hypotension, low blood pressure, fatigue, headache, drowsiness and dry mouth.

Carbonic Anyhdrase Inhibitors:

In this class we use both the topical and the oral forms (e.g. use or oral diamox in acute angle closure cases) and contraindications/side effects can vary between the two. For the topical form, there are few if any contraindications. There is a rare risk of allergic cross-sensitivity in patients with significant sulfonamide allergies that should be ascertained. Side effects include burning, stinging and eye discomfort. In the oral form however, contraindications include patients with advanced kidney disease or a history of severe sulfonamide allergy. Reports of sickle cell crisis have also been reported in oral CAI use. Side effects range from metabolic acidosis and kidney stone formation to paresthesia (tingling or ‘pins and needles’ in the hands and feet), dysgeusia (change or distortion of taste), GI upset, memory problems, depression and dehydration.
Certainly the side effects general pale in comparison to the risk of blindness but the list may help you select more appropriate medications for each patient and perhaps increase drug compliance. Contraindications should be heeded however as they range from morbidity conditions to progression of disease and even potential death. A whole new set of topical glaucoma drugs and drug delivery-system treatments are set to reach US FDA approval in the next 12-18 months. These will be a welcome addition as they seem to address new mechanisms of action or have results that exceed existing medications. They may also have a lot less systemic disease effects, which could make them ideal primary or additional therapy treatments. We’ll discuss the glaucoma pipeline in a near future PECAA e-newsletter.