At Press Time

New Findings on the Causes of Glaucoma

Study confirms similarities to Parkinson's and Alzheimer's.

■ Novel findings about the underlying causes of glaucoma have recently been published online in Proceedings of the National Academy of Sciences, in a study that confirms the beliefs of many glaucoma specialists that the disease is similar in some ways to such neurodegenerative, protein-aggregating diseases as Parkinson's and Alzheimer's. The study, which also breaks new ground in examining the characteristics of glaucoma, was largely funded by the Barr Foundation through the Glaucoma Research Foundation.

In the study (titled “Myelination Transition Zone Astrocytes are Constitutively Phagocytic and Have Synuclein Dependent Reactivity in Glaucoma”) researchers employed a range of techniques including molecular biology, electron microscopy and image analysis to uncover three interconnected new discoveries about glaucoma:

► Glaucoma reveals new similarities to Parkinson's. Glaucoma is characterized by formation of protein aggregates called gamma-synuclein. Most other neurodegenerative disorders, like Parkinson's, Alzheimer's and amyotrophic lateral sclerosis, are characterized by the aggregation of proteins. In Parkinson's disease, a very similar protein called alpha-synuclein is aggregated. This finding provides evidence that glaucoma acts more like protein aggregation neurodegenerative diseases than like other blinding eye diseases.

► New cellular mechanism discovery. Astrocytes, a subpopulation of support cells, have been found to have a highly unexpected role in cleaning up the byproducts or waste of the cells that die in glaucoma, the retinal ganglion cells. This type of “degradative” activity was not previously known to exist, and its existence may help explain perplexing findings in many neurodegenerative disorders besides glaucoma.

► Underlying cause of vision loss. Previous work by scientists had pointed to an anatomical location, the optic nerve head, where vision loss most likely occurs in glaucoma. This study is the first to pinpoint where within the optic nerve head the blinding insult is likely to be, which would explain the very characteristic pattern of blindness in glaucoma.

“These compelling results put us on the cusp of discovering a treatment for glaucoma while also being invaluable for others whose research priority is in the area of other neurodegenerative diseases,” said Nicholas Marsh-Armstrong, PhD, senior study author and a research scientist at Kennedy Krieger Institute. “Our primary goal is to find interventions that halt or at least slow glaucoma progression. We believe that understanding the underlying mechanism of vision loss in glaucoma brings us much closer to that goal. Now that we think we understand where and what the key blinding insult is in glaucoma, a number of diagnostic and treatment options become self-evident.”

Colleagues at the Johns Hopkins School of Medicine, UC San Diego, Cardiff University in the UK and the University of Murcia in Spain also were part of the research effort.

CMS Allows H&P on ASC Surgery Day

By Samantha Stahl, Assistant Editor

■ ASCs have received the green light for same-day history & physical (H&P) assessments and surgical procedures after CMS recently clarified the conditions for coverage (CfC) it released nearly two years ago.

The clarifications state that an H&P may be performed on the same day as surgery, provided it is “performed by qualified personnel, is comprehensive, and is placed in the patient's ASC medical record prior to surgery.” The H&P still may not be more than 30 days prior to surgery and cannot be performed after a patient has been prepped and brought into the OR.

However, this ruling still doesn't resolve the long-time problem for elderly and rural-area residents who have to travel long distances for two doctor's appointments, since rights must still be given to the patient at least a day prior to surgery.

“It is just wrong on every level for patients,” says Larry Patterson, MD, of Crossville, Tenn., immediate past president of the Outpatient Ophthalmic Surgery Society (OOSS), of the CfC specifications. “You've got patients who have taken off work and their vision is getting worse, so they have a family member take off work and drive an hour. Then these poor people have to drive back home and you can't do anything to help.”

The conditions have been especially troublesome in recent years, Dr. Patterson says, because of the high price of gas and transportation, combined with the slumping economy. “The government rule is actually hurting people — it's wrong for the economy, for the environment. Some-one meant well with the rule but it's based on the assumption that doctors are evil and patients are stupid.”

CMS also stated that the comprehensive H&P may now be combined with some elements of the pre-surgical assessment. This is not applicable to the anesthetic/procedure risk assessment, which still must be performed immediately prior to surgery.

OOSS is still working to find a more specific definition of “comprehensive,” according to Michael Romansky, the society's Washington counsel, so that doctors can have more definitive guidance for the new CfC regulations.

Dr. Montzka: Changing Ophthalmic EHR

His physician-designed, cloud-based system attracts buyers.

By Jerry Helzner, Senior Editor

■ Florida-based retina specialist Dan Montzka, MD, 49, has always been something of a “techie.” At the University of Minnesota he was an engineering major. As a fellow at Wills Eye Hospital, he was instrumental in putting instructional material into a CD-ROM format. So it should not come as a surprise that when he looked at the available ophthalmic-specific EHR systems over seven years ago, he thought he could design something better and more physician-friendly.

“For example, as ophthalmologists, our patients are older and often present with significant pathology,” notes Dr. Montzka. “The EHR systems I looked at utilized static templates that were pre-defined or user defined,” which he found limiting in terms of clinical documentation. “It's impossible to anticipate the countless combinations and permutations of disease that patients may present with.” He addressed this issue with patient-specific adaptable templates that can significantly reduce typing while generating granular data. “It's not perfect but does allow for significant improvements in the speed and specificity of clinical documentation.”

Dr. Montzka's initial effort, first installed in his own practice, was good enough to attract five other practices that purchased the system. “I started with a client-server system, which was the only option at that time,” recalls Dr. Montzka. “But I was also talking to some venture capital groups who said that Web-based software was going to be the wave of the future.”

Dr. Montzka persisted with the client-server model for a while. “I did not believe that Web-based software was robust enough to handle the significant demands of EHR software. But conversely, I was becoming increasingly frustrated with the slow, costly development cycles on the client-server platform.” At just about that time, he found a kindred spirit and fellow innovator in Roland Feijoo, who had been developing his own company, Extensys, to achieve critical capabilities in managing IT infrastructure, providing system security and in Web hosting. Dr. Montzka and Mr. Feijoo soon merged their companies to form MDIntellesys.

Dr. Montzka checks an OCT image on the MDIntellesys EHR system.

“Dr. Montzka had deployed some absolutely ingenious solutions to complex issues, but it was on a legacy technology platform,” says Mr. Feijoo. “We agreed to partner with Dr. Montzka based on a move to cloud computing technologies and the development of a new business model.” After committing to the new direction, Dr. Montzka determined it was in the best interest of current and future customers to stop selling while they retooled everything to enable delivery on a secure cloud, including building out two data centers, a year-long risk that has “totally paid off,” Mr. Feijoo says.

“The merger with Extensys was our key to success,” asserts Dr. Montzka. “When medical practices run into problems with EHR, often it isn't the software. Quite frequently, it's the IT infrastructure that they struggle to manage. With Extensys, we have full control of the IT infrastructure.”

Plus, the merger with Extensys allowed MDIntellesys to offer its customers a cloud-based EHR that requires no big upfront investment for hardware, charges only monthly fees based on the number of practitioners using the system and operates with no contracts. The MDIntellesys EHR also has an HL-7 integration system and is compatible with many client-server EHRs and Web-based practice management systems.

“Essentially, we handle all security and support services,” Dr. Montzka says. “All the practice has to do is provide Web access. Our imaging module is very popular with our users and can handle multiple FAs and OCTs.” Due to bandwidth considerations, images are stored at resolutions optimized for computer display and not full-page high-resolution printing. However, clinics have access to their images from any computer with an Internet connection. Most users are very willing to accept this trade-off, he says.

The ophthalmology-specific system has been attracting much interest, with inquiries growing exponentially and more than 50 systems currently installed, including Queen's Hospital in Ontario. The system is applicable to all ophthalmology practices.

Another benefit is that the system allows users to exchange new ideas, treatment approaches for difficult cases and basic insights through a proprietary database that has been likened to an ophthalmology-based Wikipedia — driven by the physicians who contribute the information.

“Our company is now working with the Drummond organization to have our system certified,” says Dr. Montzka. “We are fully committed to achieving and maintaining certification so that practices that use our system can receive full ‘meaningful use’ bonus payments. However, we view the bonuses as simply an added benefit and should only be one of many considerations when choosing an EHR.”

The primary reason to consider a cloud-based system is not cost savings but “the significant added value of an easily updated, collaborative solution,” asserts Dr. Montzka. “We are just beginning to tap into the potential of cloud-based EHR systems that leverage the combined resources of a community of users.” He asserts that “it is only a matter of time until all high-end EHR systems will be cloud-based.”

In any event, the cloud-based model is catching on quickly, with both GE Centricity and AthenaHealth indicating that they are planning to launch ophthalmology-specific cloud-based EHR in the next year. Established ophthalmic-specific EHR providers such as NextGen and Medflow will also be offering cloud-based alternatives to their client-server systems.

Meanwhile, Dr. Montzka still maintains an active clinical practice but has found it necessary to reduce his clinical hours to keep up with his duties as CEO of MDIntellesys. “The shift is going to continue as the company grows,” says Dr. Montzka. “But my focus is on making our system more efficient for physicians and that can only happen if I continue to be involved in clinical practice.”

More information is available at www.MDIntellesys.com.

For an examination of the pros and cons of cloud-based EHR, please read the Path to Paperless column of this issue.

Research Digest

New & Noteworthy Journal Articles

Compiled by Andrew E. Mathis, PhD, Medical Editor

► Oxidative stress in glaucoma. With increasing emphasis in medical research placed on oxidative stress and the role it plays in a variety of diseases, the ability of drugs to prevent oxidative stress may provide an edge when physicians choose treatments for patients. Therefore, findings by an Italian team of ophthalmologists regarding the ability of dorzolamide hydrochloride and timolol maleate to display antioxidant effects may give these drugs an edge in glaucoma therapy.

Reporting the results of a study in the January 2011 Archives of Ophthalmology, the Italian team found that timolol had antioxidant effects on trabecular meshwork cells when those cells were exposed to hydrogen peroxide to maximize their oxidation. Furthermore, dorzolamide not only protected against oxidative stress at two levels of hydrogen peroxide exposure, but it also demonstrated protection of the DNA of trabecular meshwork cells. When the drugs were used in combination, their antioxidant effects were increased.

Given the established link between glaucoma and oxidative stress-induced damage to DNA, these findings are likely to give a boost to combination therapy with dorzolamide and timolol, with Merck's Cosopt combination of the two drugs.

► Cataract and dementia. Everyone knows that both acquired cataract and dementia are age-related diseases, but are they at all related? With an article in the January 2011 issue of the British Journal of Ophthalmology, ophthalmologists and gerontologists from the United Kingdom have reported the results of a literature review conducted to determine whether an association exists.

The study team searched articles studying cataract, dementia and cognitive impairment over a 60-year period. While they were not able to conclude that there is a common etiology for cataract and dementia, they nevertheless confirmed several long-held beliefs about the two disorders, notably that there are clear links between neurodegenerative disorders and visual impairment and that patients with dementia are subject to poorer outcomes from phacoemulsification.

The article ends with several practice pearls, including a call for a multidisciplinary approach to treating cataracts in patients with neurodegenerative disease. The authors state that, because there is an overlap between dementia and visual symptoms, diagnosis of both disorders may be more difficult when they are comorbid.

► Not the most valuable player. Among the most common causes of heart murmur is mitral valve prolapse (MVP), which, while in most cases is a minor valvular heart disease with a low risk of complications, can still lead to serious complications, including cardiac arrest.

Noting an association between MVP and patients with keratoconus, a team of Iranian physicians undertook a study of 160 patients to determine whether an association exists between MVP and corneal hydrops, which affects 5% of patients with keratoconus. They report their results in the February 2011 issue of Cornea.

Of the 160 participants in the study, 32 patients had keratoconus with a diagnosis of acute corneal hydrops, and the other 128 patients were controls. All subjects underwent cardiac evaluation and two-dimensional echocardiography to determine whether MVP was present. Not only was the rate of MVP over six times higher in the group with corneal hydrops (65.6% vs. 9%), but the results were verified as statistically significant using two methods.

The authors of the study stress that, while they included a control group four times as large as the active disease group to increase the power of their study, more research on the correlation between corneal hydrops in keratoconus and MVP is needed. However, given the possible severe complications associated with MVP, they advise that all patients diagnosed with keratoconus with corneal hydrops be screened for MVP.

► Anti-VEGF injection safety. With wet AMD now being treated overwhelmingly with intravitreal anti-VEGF injections and with some general ophthalmologists performing these injections, particularly in geographic regions with few retinal specialists, assuring the safety of these injections is more urgent than ever before.

The phase 3 SAILOR trial of ranibizumab found a small but non-statistically significant link between 0.5 mg injections of ranibizumab and stroke. These results were reported two years ago; are there newer safety data to consider?

An article in the January 2011 issue of Retina by a team of retinal physicians at the University of Iowa seeks to answer this question. Undertaking a study of 102 patients receiving bilateral injections of either ranibizumab and/or bevacizumab and an equal number of control patients receiving unilateral injections, and following up these patients for an average of 18.4 months, the study found no significant link between intravitreal anti-VEGF injections and thromboembolic events.

Furthermore, there were no cases of injection-related endophthalmitis — in fact, no cases of endophthalmitis at all — and no cases of stroke. And, while there was one case of myocardial infarction in each arm of the study, neither case was linked to the treatments. Similarly, five deaths occurred in both groups combined over the total of 23 months of the study, but none of these deaths were caused by the treatment.

The authors hope that their results will help lessen the treatment burden to both patients and ophthalmologists by providing more data that same-day bilateral injections are safe. OM