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Clinical Updates on Managing Infectious Keratitis

 

 

Corneal infections and subsequent opacities, largely caused by infectious keratitis, are the 4th leading cause of blindness worldwide. In the United States, infectious keratitis is especially seen with extended contact lens wear, though in developing countries ocular trauma remains the leading etiology. Typically, bacterial keratitis develops when the ocular surface has been compromised. However, some bacteria are able to penetrate an intact epithelium, i.e.- Neisseria gonorrhea, Neisseria meningitis, Corynebacterium diphtheria, and Haemophilis influenza.

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 Proper diagnosis is paramount to initiating adequate treatment protocols and achieving clinical resolution. Currently, corneal cultures are the mainstay in identifying the underlying pathogen. Below are common cultured stains used to identify pathogens:

 

  • Gram and Giemsa stains: bacterial and fungal cases

  • Blood and chocolate agar: bacterial (most commonly used) and some fungi

  • Sabouraud’s agar: fungal

  • Non-nutrient agar with Escherichia coli overlay: Acanthamoeba

  • Polymerase chain reaction: viral (rarely used, often diagnosed on history/examination)

 

As mentioned, keratitis can be segregated into one of three categories: bacterial, fungal, and viral keratitis (though bacterial and fungal infection can coexist). We will now describe each pathogen with preferred therapeutic options from scientifically supported clinical trials.

 

Bacterial Keratitis

 

Treatment with Antibiotics

 

            Treatment with topical antibiotics is the preferred therapy in achieving resolution of an infection. Antibiotic monotherapy has an advantage over duotherapy in lowering the risk of ocular surface toxicity as well as increasing patient compliance. Commercially available fluoroquinolones are typically preferred agents to treat bacterial keratitis and are regarded as being as effective as duotherapy.

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In very aggressive diseases, duotherapy may be desired and usually involves a combination of two fortified antibiotics (i.e.- a cephalosporin and an aminoglycoside) to cover for Gram-positive and Gram-negative pathogens respectively. Fortified antibiotics have several disadvantages including cumbersome compounding, higher cost, risk of contamination, limited availability, short shelf life, and the need for refrigeration.

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 In a recent study, bacterial keratitis was managed in 16 trials over the period of 7 days that compared moxifloxacin vs. ofloxacin vs. tobramycin/cefazolin (fortified antibiotic). The research showed that while there was occasionally mild ocular discomfort when instilling the aminoglycoside-cephalosporin antibiotic compared to the fluoroquinolones, there was no significant difference on the time to re-epithelialize the cornea or on time to cure. Of note, moxifloxacin demonstrated superior corneal penetration.  

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            Antibiotic resistance is a growing concern when treating infections. Not only are 2 million people infected with drug resistant microbes annually, 80% of methicillin-resistant Staphylococcus aureus in the United States are resistant to the fluoroquinolones, the most commonly prescribed antibiotic class. As previously stated, in patients diagnosed with bacterial keratitis who are not improving on fluoroquinolones, switching to fortified broad-spectrum antibiotics is advised.

 

Implications: Fortified antibiotics are rarely preferred to commercially available fluoroquinolones. In patients who truly need fortified antibiotics, consider starting them on fluoroquinolones until the compounded antibiotics can be obtained.

 

            In an acute infection, fibroblasts, keratocytes, and other inflammatory cells can result in corneal melting and potential corneal perforation, increasing the incidence of severe infectious keratitis. Tetracyclines, well known to inhibit matrix metalloproteinase-9 responsible for protein degradation and keratolysis, reduce the rate of corneal perforation. In two rabbit studies, high-dose systemic tetracycline reduced corneal ulceration from 85% to 9%; a separate study systemic doxycycline reduced the rate of cornea perforation from pseudomonas by 50%. We recommend prescribing 100mg of doxycycline at the initial encounter (along with topical therapy as previously discussed).

 

Treatment with Steroids

 

            The large, randomized, controlled Steroids for Corneal Ulcers Trial (SCUT) study compared adjuvant topical corticosteroids with placebo for treating bacterial corneal ulcers. While steroids did not show any significant benefit overall, they did prove advantageous in ulcers that were central, deep, large, non-Nocardia, or in cases of Pseudomonas. Nocardia, an atypical bacterium, was seen in 10% of all ulcers in SCUT. Subjects randomized to corticosteroids with Nocardia fared far worse than placebo, as a larger infiltrate or scar was present at 3-month follow up.

 

Implications: Based on the results of SCUT, adjuvant topical steroids in non-Nocardia cases are recommended after 48 hours of selective antibiotic therapy.

 

Fungal Keratitis

 

Treatment with Topical Anti-Fungals

 

            Due to their unique microbiological structure and physiology, fungal ulcers are more difficult to treat, and have worse outcomes than bacterial ulcers. Also, fungal keratitis diagnosis is typically delayed as the offending pathogen is usually presumed bacterial. Since natamycin was FDA-approved in the 1960s, no other topical eye drop to treat fungal keratitis has been developed. As with bacterial keratitis, contact lens wear is also an important risk factor for developing fungal keratitis.

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            Though natamycin 5% is the preferred topical treatment option in fungal infections, its efficacy is somewhat hindered by its poor corneal stromal penetration. Amphotericin B 0.3% to 0.5% are viable alternatives but require a compounding pharmacy that are not always readily available.

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            In the Mycotic Ulcer Treatment Trial I (MUTT I), topical 5% natamycin and topical (compounded) 1% voriconazole were studied in the treatment of filamentous fungal ulcers. The results of natamycin compared with voriconazole was so astounding that the Data Safety Monitoring Committee urged to cease treating those taking voriconazole due to a statistically significant increase in corneal perforation and severe complications. Patients taking natamycin had a better BCVA and smaller scar size at the 3-month follow up than those treated with voriconazole. Further evidence showed that on day 6 of treatment, a higher percentage of patients still cultured positive for fungal infection with voriconazole compared to natamycin.

 

Implications: Topical voriconazole is inferior to topical natamycin in the treatment of all fungal infections as evidenced by the MUTT I.

 

Treatment with Oral Voriconazole

 

            The Mycotic Ulcer Treatment Trial II (MUTT II), sought to investigate potential benefits of oral voriconazole compared to oral placebo. The shortcomings of topical voriconazole were exposed once again, with oral voriconazole providing higher and more constant doses than topical voriconazole. In a study comparing oral and topical voriconazole, testing after topical administration showed large variability in aqueous concentrations “with troughs well below the minimum inhibitory concentration at which 90% of fungal isolates are inhibited (MIC90).” MUTT II discovered no major advantage to treating with oral voriconazole compared to placebo, with significantly more adverse effects when oral voriconazole was employed.

 

Implications: Topical natamycin remains first-line therapy over oral and topical voriconazole in the treatment of filamentous fungal keratitis as evidenced by MUTT I and MUTT II. Additionally, there was no benefit of adjuvant oral voriconazole.

 

Viral Keratitis

 

            Unlike bacterial and fungal keratitis, viral keratitis has the ability to be both chronic and recurrent. The leading cause of corneal blindness in the world, herpes simplex virus keratitis (HSV-K) affects 500,000 individuals in the United States alone. In developing countries, 60% of all corneal ulcers are noted to be the result of the herpes simplex virus. Globally, the lifetime risk of developing HSK is 1%.

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Because of the virus’ ability to relapse, a persistent impairment on the quality of life for individuals who have been affected is well documented. Forty percent of patients will experience 2 to 5 relapses in their lifetime, with 11% of those experiencing 6 to 15 relapses. Even during the quiescent phases of the disease, psychological impairment is similar to that of sight-threatening diseases like glaucoma and macular degeneration.

 

Treatment with Topical Antivirals

 

            There are two FDA-approved topical agents to treat HSK: trifluridine (Viroptic) and ganciclovir (Zirgan). Trifluridine is more commonly prescribed due to its generic availability, though it does carry a higher propensity for ocular surface toxicity.

 

Implications: While ganciclovir is a newer drug with enhanced broad-spectrum antiviral coverage, its use it somewhat prohibitive due to cost. Thankfully, there are coupons available to make Zirgan more affordable.

 

Treatment with Topical Steroids

 

            In the Herpetic Eye Disease Study I (HEDS I), the efficacy of adjuvant corticosteroids to treat HSV stromal keratitis was researched over a 10-week period. While visual acuity was similar with those treated with topical corticosteroids compared to placebo after 6-months, the placebo group paled in comparison when analyzing HSK time to resolution.

 

Implications: HEDS I showed faster resolution of infection by adding topical corticosteroids with trifluridine compared to trifluridine alone when stromal keratitis was present.

 

Treatment with Oral Steroids

 

            The adjuvant use of oral acyclovir was also analyzed as a treatment protocol for HSV stromal keratitis. In this study, 104 patients taking topical trifluridine and corticosteroids were randomized to receive oral acyclovir or the placebo. The addition of oral acyclovir resulted in a significantly significant increase in vision after 6-months compared to placebo.

 

Implications: Oral acyclovir provided improved vision after 6-months of use to decrease stromal keratitis.

 

            Oral valacyclovir, a prodrug of acyclovir, has an enhanced ability to penetrate the cornea with a less-frequent dosing schedule compared to acyclovir.

 

Implications: To avoid ocular surface toxicity, oral antivirals are often preferred to topical antivirals, and work equally as well. Further, oral acyclovir at 400mg 5xD or valacyclovir 500mg TID is the least expensive medical therapy.

 

 

Oral Prophylaxis

 

            In the Herpetic Eye Disease Study II (HEDS II), prolonged use of oral acyclovir was researched to examine rate of recurrent ocular HSV. In those taking oral acyclovir, the risk of HSV recurrence was 45% lower compared to placebo.

 

Implications: A long-term, low dose of oral acyclovir decreases the risk of developing recurrent HSV stromal keratitis. The dosage is either acyclovir 400mg BID or valacyclovir 500mg QD for “5-disease free years.”

 

New Treatments on the Horizon

 

Collagen Cross-Linking (CXL)

 

            Collagen cross-linking is gaining popularity to help treat a spectrum of corneal ulcers. In CXL, photochemically activated riboflavin strengthens collagen bonds and molecules in the cornea, improving the resistance to enzymatic degradation while providing antimicrobial effects.

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            In a small case study, 16 patients with bacterial keratitis were treated only by CXL. Out of this sampling, 14 of the patient’s ulcers resolved with out any adjuvant therapy. Only 2 required topical antibiotics to resolve the infection. If more research can prove the effectiveness on CXL, perhaps this model will help address the current drug-resistant therapies that plaque millions of affected patients worldwide.

 

           

 

References:

 

  • Austin, et al. Update on the Management of Infectious Keratitis. Ophthalmology. Vol 124, Number 11, Nov 2017.

  • Bowling, Brad. Kanski’s Clinical Opthalmology.

  • Reynaud, et al. Persistent Impairment of Quality of Life in Patients with Herpes Simplex Keratitis. Ophthalmology. Article in Press.

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The Optometric Cardiologist

 

      Cardiologists are superbly trained medical practitioners of the heart, and cardiothoracic surgeons are superbly trained in heart/chest surgeries. These two medical specialties work together as smoothly as a well-oiled machine or as finely tuned instruments in an orchestra. Why, then, is this not the case with ophthalmologists and optometrists in eyecare? There may be several reasons – a couple follow, and the dynamics here can be highly complex: One reason is that general ophthalmologists are by and large heavily focused on cataract and refractive surgeries. Since many have not (through professional “racism”) enjoined the community optometrists as surgical referral sources, ophthalmologists have to see an abundance of general care patients to glean their surgical patients . Ophthalmologists are heavily, procedure-oriented by definition and by choice; they are eye surgeons. Being procedure-oriented, they are not bastions of medical eyecare. There is no analogous medical specialty in ophthalmology, only a surgical residency. Note that it is a high bar to be competent in both medical and surgical aspects of any specialty. To wit:

Neurology and neurosurgery 

Sports medicine and orthopedic surgery  

Rheumatology and orthopedic surgery  

Internal medicine and general surgery 

Gastroenterology and general surgery

Nephrology and urology

Pediatrics and pediatric surgery 

Audiology and otolaryngology 

There has always been a major sequestration between medicine and surgery, as they are clearly two distinct elements of patient care.

 

      Optometrists, at least traditionally, are heavily focused on refractive correction of ametropias with eye glasses and contact lenses. Ophthalmic medicine has not, until recently, held sway in professional training and competency. As a profession, we have not historically been trained to be a medical eye physician. So, from both an ophthalmologic and optometric perspective, “medical eyecare” has been relatively ignored. Now, optometry is continuing to grow in its embrace of medical conditions of the eye, and ophthalmology, though trained in eye medicine and eye surgeries, is now far more keenly focused on surgical procedures.

      If eyecare can continue to evolve in parallel to every other aspect of medicine, optometrists should become the cardiologists of the eye, and ophthalmic surgeons will be fully ophthalmic surgeons. Of course, this will require the continued revision of optometric curriculum to more comprehensively embrace the entire spectrum 

 

The Optometric Cardiologist: Page 2

 

of medical eye disease, and to ophthalmology devoting itself exclusively to meeting the coming “baby boomer” demand for cataract and refractive surgeries.

 

      Finally, in addition to the American Academy of Ophthalmology, there is a huge meeting and journal exclusively dedicated to “cataract and refractive surgery”. There is no huge meeting or journal dedicated to “medical ophthalmology,” nor should there be, especially if the profession of optometry rises to fill this relative void in human patient care. 

 

Optometry as a Commodity

 

      Optometry has experienced glorious growth in the scope of professional practice over the past few decades. Interestingly, those who practice in small towns may have gained more from the broadening of services offered than those in more urban areas. There are many hundreds of optometrists who truly function as comprehensive eyecare physicians delivering state-of-the-art eyecare. There are also many thousands of optometrists who function as glorified refractionists, mostly in urban, retail type settings. These optometrists are relegated (either by choice or by necessity) as “refract and refer” practitioners. Like it or not, most ophthalmology offices have a team of well-trained high school graduates who perform excellent refractions, and the ophthalmologist (s) serve as the “quality control officer” who oversees their findings and performs the balance of the comprehensive eye examination.  

 

      It seems a deplorable waste of four years of postgraduate training, time, talent and money, only to spend one’s professional life doing the same tasks that most high school graduates can be trained to do in six to twelve months.

 

      From an optometric perspective, this situation is likely to worsen as a tide of new optometry schools flood the market, driving up competition for positions while diminishing potential incomes. It may not be long until new graduates, burdened with increasing college debt, will find less opportunity to land desirable positions with desirable remuneration.

 

      Refracting technology devices have rapidly evolved, and their level of accuracy is now well within visual acceptance standards. We can see the day when refraction will be offered at kiosks in shopping malls for $25 to $50; the patron will simply sign an electronic “release from liability” statement that may read something like: “This prescription for eyeglasses does not constitute a comprehensive eye examination. You should be examined by a licensed ophthalmologist or optometrist to assure that an eye disease/condition such as glaucoma, cataract, or macular degeneration, is not present.” I assure you, the statement will be filled with all the correct legal jargon. Currently, tobacco, alcohol, and a myriad of other products and services are sold with similar warnings. All such disclaimers minimally affect human behavior, but medicolegally, these statements in most instances serve well to protect the entrepreneur.      

 

      Physical care doctors – and you have to decide if you bear the honor of such a mantle – should have the patient’s very best interest at heart. Unfortunately, many “doctors” in the eyecare profession  are in essence, “eyeglass salespersons”, and are violators of the Golden Rule. Courses and articles that instruct one on “how to up-sell your optical” are a disservice to the consumer and to the eyecare professions as a whole. These 

 

Optometry as a Commodity: Page 2

 

tactics are not compatible with the concept of “doctor” and they violate our duty and responsibility to be a trusted healthcare provider to other humans who count on us for help. 

 

      One measure of optometric productivity is the “currency” of our patient census. If we measure our productivity in “eye exams,” we will be doomed by technology. If, however, we measure our productivity as the “number of patients seen,” there is hope. Many optometrists see 25 to 30 patients per day, and perhaps half of these patients are indeed, “healthy eye exams,” but the balance are problem-oriented visits for such conditions as posterior vitreous detachments; acute red eyes; dry eyes; blepharitis; shingles; trichiasis; contact lens-related problems; foreign body; abrasions; glaucoma; Plaquenil toxicity; contact dermatitis/rosacea; epiphora; headache; temporal arteritis; optic neuritis; diplopia; cataract; hyphema; glaucoma (repeated with intention);  symptomatic tarsal conjunctival concretions; episcleritis; and the list goes on and on! “Refract and refer” optometrists may wither on several levels, but true comprehensive, patient-centered optometric physicians should flourish. Established optometrists,  and particularly those contemplating optometry as a career, should thoughtfully weigh the concepts and perspectives set forth in this article.

 

      In summary, with excellent externships, it is possible to complete a four-year, doctorate-level, single-organ system program with sound clinical competence. Refractionists will be relegated to “factory work,” while comprehensive optometric physicians can have an exciting, diverse clinical life full of satisfaction and yes, financial success. The former will be sales-oriented; the latter, patient-oriented. The former’s practice could be dampened by refractive technology advancements; the latter can look forward to a career enhanced through advances in diagnostic technology and therapeutic options.  It’s up to you.

 

 

 

Our Perspective on the Future of Our Profession

 

If something unsightly is stuck between your front teeth, it is a true friend who steps outside his or her own comfort zone to tell you, so that further embarrassment is avoided. In like manner, we are stepping outside of our comfort zone to offer our perspective on the future of optometry. There needs to be a clear awakening regarding our collective mode of practice before we cross the threshold into professional disaster.  There are several observations that we share:

  1. Refraction. Once the epicenter of optometric practice, refraction is actually a technical procedure that can easily be delegated to bright high school graduates after several weeks of training.  Let’s put this into real time perspective: ophthalmologists have huge practices, and commonly see twice the number (or more) of patients per day than do optometrists. People flock to ophthalmology practices because there is the strong perception that ophthalmologists are “real eye doctors” and the public harbors great trust in the belief that they receive higher quality of eye care at these practices; although in many of these practices, trained high school graduates do indeed provide the refractive portion of the examination. So, if “refraction” is such a high-value service, how can this procedure be so successfully delivered by high school graduates?! Now, granted, the physician, either optometric or ophthalmologic, has a duty and responsibility to oversee the entire patient care process and provide rock-solid quality assurance. Further, and perhaps even more importantly, “technology” is like a two-edged sword – it has advantages and disadvantages, such as one’s level of competency in the use of that technology. 

Autorefractors are now able to provide highly exact prescriptions.”Online (or kiosk) refractions” are likely to soon become a reality. Of course, these devices/websites will carry a disclaimer stating something like this: “Receiving a glasses prescription from this device/website does not constitute a comprehensive eye examination, and all persons should receive a formal eye examination from an optometrist or ophthalmologist periodically” – or some similar statement that will be largely ignored, as are the health warnings on alcohol and tobacco products. Moreover, 3-D printers can now generate eyeglasses, and this technology will only continue to improve.

 

  1. The American Aging Population. The American population is ageing, while ophthalmology residency programs are being reduced. There will be a growing need for all aspects of medically-related eye care in the coming years.  Ophthalmologists love performing microsurgeries, but many have little or no passion for nonsurgical eye care. Since ophthalmologists will have their hands full providing cataract and refractive surgeries to our older citizens, there will be a major void of clinicians to care for those patients in need of nonsurgical eye care services. The optometric profession could easily fill the gap. 

 

Our Perspective on the Future of Our Profession: Page 2

 

  1. Specialty Contact Lens Care. Specialty contact lens care is likely to endure as a needed professional service, but most of these contacts will likely be purchased online at a competitive price. However, basic soft lens care could be provided by optical dispensaries or contact lens technicians in ophthalmology offices.

 

  1. Optometric Education.  In truth, we probably have way too many optometry schools. Why “probably”? If the educational institute’s purpose is to provide training in medical eye care, then terrific. There will be a huge number of necessary services that their graduates can fulfill. However, if the facility is just another “me, too,” traditional, refractive-centric school, they are pathologically flooding a market in which the mode of refractive eye care services appears to be changing. As schools produce a glut of freshly minted optometrists, the salaries for optometric services will be suppressed. It may be that ophthalmology practices could hire a “basic” optometrist at only a slightly higher salary than that of an ophthalmic technician. However, we believe a well-trained, medically competent optometrist should be and would be a highly valued asset to medical/surgical systems. Just something to think about.

 

  1. Optometric Curricula. Optometric  curricula and our “Board” examinations need to immediately be modified to reflect this new age of need for medical expertise within our profession. These two institutions (the schools and the boards of examination) need to evolve in parallel fashion so that training and testing  share the parallel goal of total competence in specialty contact lenses and comprehensive medical eye care, as we believe these will be critical for our professions meaningful  survival in the future.

 

The time is now for all interested parties in healthcare and optometric care to give actionable thought to these concepts and perspectives we have set forth. We will be retiring in a few years, but we have a deep desire to see our profession continue to advocate for enhanced public health. Our current status is in need of a major paradigm shift. We stress that anything we do to strengthen our profession cannot be self-serving. Our profession will thrive because of our collective effort as well-trained, dedicated doctors of optometry to provide broad-based, expert patient care.  

 

 

 

 The BEST Way to Stay Current (It’s NOT With a Lecture Format!)

 

      The best way to stay current is quite simple: get four to six area colleagues to each subscribe to a single journal or magazine. Then get together over a nice meal once a month to share the pertinent highlights of each month’s journals. This should take about two hours, and will make all of you much better doctors.

      The journals we subscribe to, and recommend are as follows:

  • Ophthalmology 

  • American Journal of Ophthalmology 

  • JAMA – Ophthalmology 

  • Survey of Ophthalmology  

Beyond these essential four, there is Review of Optometry, Primary Care Optometry News, Optometric Management, and many others from which to choose.

Simply Google these publications to subscribe. The meals and subscriptions are tax-deductible; the education and fellowship is priceless!

 

 

 The Eye in Public Health

 

      Politically-oriented ophthalmologists so enjoy railing against optometric scope of practice legislation, alleging potential harm to public health. They are so terribly wrong. We all know how poor eyecare is at “quick care/urgent care” centers, and even in hospital-based emergency departments and primary care offices. All optometrists and ophthalmologists are fully aware of the substandard eyecare rendered in these facilities. Not all urgent or emergent eye problems occur during regular office hours, so we have some sort of general safety net for these after-hour patients –the hospital-based emergency department at least fills the “first responder” role for these events.

 

      Now, regarding protecting the public health, IF the eyecare professions, and especially ophthalmology, truly cared about the public’s health, rather than devote energy to trying to limit optometric services, wouldn’t the common good be better served by developing guidelines, policies and protocols, and legislation advocating that patients with eye and vision problems preferentially be seen by eye doctors? It should be quite obvious that steering eye patients to practitioners who can provide higher levels of care could enhance public health. The time is now to cease such hypocrisy and duplicity, and focus on measures to enhance the eyecare of the citizens we profess to serve. Something to think about.

 

 

CE: Continuing Education or Infomercial?

 

            The reality is that many continuing education lectures are a sham; a commercial for one or more companies.  There are several reasons for this: continuing education would be significantly more expensive were it not for industry sponsorship dollars; some optometrists are present only to “get my hours,” and simply want to get their ticket stamped and get home; state associations may care more about their budgets than they do about the true education of  their members, and these associations therefore tend to seek “sponsored” lecturers. That is, some state associations may be willing to sacrifice the quality of education for financial stability. Some optometrists may not be current with the scientific/medical literature, and so may be easily manipulated by company-sponsored lecturers.

 

      The misleading statement, “the speaker has no financial interest,” is grossly misleading! While the speaker may not own stock in a specific company, she/he is most assuredly under obligation to promote the product/device of the sponsoring company. If the speaker does not perform to the sponsoring company’s expectation, that speaker will rapidly be replaced by a more compliant lecturer. Thus, lecturers speaking for any company have a very real financial interest in the content, purpose, and delivery of the lecture.  For instance, if a sponsored lecturer speaks factually about the virtues of a Lexis, then that is fine because it’s true; but if a lecturer portrays lesser quality care as equal in value or ability, then an egregious disservice is perpetuated against the audience.  As lecturers ourselves, we speak regularly on behalf of Bausch & Lomb Pharmaceuticals, yet we share the truth of the clinical benefits of these products. We do not “sell,” but truly educate our audiences with the goal of enhancing patient care.  It is fully ethical to urge the use of a product when it truly enhances patient care, but when a product has either marginal or no benefit to patient care, such a lecturer is fully unethical.

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