The Eyes Have It – Concerns About Ophthalmic Medications – Medical Journal Of Australia

Topical ophthalmic medications have the potential to cause significant systemic side effects and to seriously interact with oral medications, according to an editorial in the 6 October issue of the Medical Journal of Australia.

Associate Professor Ivan Goldberg, from the Sydney Eye Hospital, and his co-authors said many Australians are prescribed topical ophthalmic agents for chronic conditions such as glaucoma, ocular inflammation, infection and allergy.

While the overall safety of these agents is recognised, there is a potential for serious side effects in a small proportion of people. As well as their own direct effects, topical agents may have significant additive or interactive affects with systemic medications.

In many cases, these effects go unreported by the patient or are misdiagnosed.

“Topical steroid drops are key to the management of ocular allergy and inflammatory disease. While they are well tolerated systemically, their ocular side effects are potentially blinding: potentiation of infection, cataract and glaucoma. Commonly perceived as a ‘safe’ alternative, fluorometholone has been associated with all these ocular side effects, albeit less frequently,” say the authors.

Although topical chloramphenicol is commonly prescribed to treat infective conjunctivitis and is used perioperatively with ocular surgery, its potential to induce life-threatening aplastic anaemia remains controversial. Concern about this risk has been enough to marginalise its use in the United States, according to the authors.

In view of recent legislative changes allowing practitioners who are not medically trained to prescribe topical ophthalmic medications, it is timely to remind all health care practitioners of the potential hazards of these medications, say the authors.

“There is a need for improved prescribing practices in both the ophthalmic and general medical communities, with increased awareness of the full range of therapeutic agents being taken by the patient.”

A separate article in the same issue of the Medical Journal of Australia discusses the case of a man in his 70s with melancholic depression induced by ??-blocker antiglaucoma agents.

Professor Isaac Schweitzer, from the University of Melbourne’s Department of Psychiatry, and his co-authors say that depressive side effects of antiglaucoma agents may be overlooked in older patients because depression is often dismissed as a normal reaction to ageing, loss or chronic illness.

The article emphasises that even a drug that is administered topically, such as antiglaucoma eye drops, is absorbed systemically and could potentially cause adverse affects elsewhere, including centrally.

Prof Schweitzer says that, as there are alternative antiglaucoma medications, it is prudent not to prescribe ??-blockers for patients who have a history of depressive illness.

“If depression develops after the commencement of a ??-blocker antiglaucoma agent, an alternative medication should be substituted if possible,” he says.

Medical Journal of Australia

National Federation Of The Blind Wins Campaign, UK

The National Federation of the Blind of the United Kingdom welcomes the Government’s announcement that they will change the regulations of the Disability Living Allowance to allow Blind people to receive the higher rate of the Mobility Component of the DLA benefit from 2011.

The Federation’s ten-year campaign to have blind people included in this benefit has been helped in the last three years by the Royal National Institute of Blind People.

However, it was the Federation’s long-term campaign, encouraging other organisations to join the campaign, that has led to this success.

Jill Allen-King M.B.E. who was the only blind member of the DLA Board when it was set up in 1992, and has campaigned for the regulations to be changed ever since, said:

“It was very unfair that a person who was virtually unable to walk was able to receive the higher rate of the Mobility Component of the Disability Living Allowance, and yet blind people could only receive the lower rate. That was a difference of ??30 per week.”

The Federation would like to thank all its members and friends and their members of parliament who have, over the years, supported them.

The Federation would also like to thank its Patron, Professor Ian Bruce who, in his last year as Director General of the RNIB, agreed to make this a high profile campaign which led to two successful mass lobbies of parliaments. Federation members, who are all blind and partially sighted, travelled from all parts of the country to take part in these lobbies.

Blind people have to spend so much money on taxis to take them to their shops, doctors, churches, and social activities, that this higher rate of benefit will certainly go a long way to help them to be more mobile and independent.

National Federation of the Blind

Patient-Reported Outcomes May Be Used In Medical Product Development

The National Eye Institute (NEI) and the Food and Drug Administration (FDA) are sponsoring an October 13 conference to determine how vision-related patient-reported outcomes might be used to improve medical product labeling in ophthalmology.

Patient-reported outcomes are being incorporated more frequently into randomized clinical trials. A growing body of evidence strongly suggests that such patient-reported outcomes are key to providing a better understanding of treatment outcomes, beyond the data obtained from visual acuity or visual field measurements. The FDA is already incorporating this type of patient-reported information into medical product labeling in areas outside ophthalmology.

This meeting, part of an NEI/FDA series of Endpoints Symposia managed by the Association for Research in Vision and Ophthalmology (ARVO), will explore the issues and challenges related to patient-reported information in ophthalmology. Participants will also look at FDA guidelines for using patient-reported outcomes and how they are incorporated for medical devices and drugs.

Faculty will include authorities in instrument development, refractive surgery, cataract surgery, glaucoma and retina. FDA representatives will present insights about how the FDA reviews and evaluates patient-reported outcome in support of product labeling for instruments and ophthalmic drugs and biologics.

Visit arvo/endpoints09 to download the full agenda, including faculty, and to register.

This meeting is being managed by the Association for Research in Vision and Ophthalmology.

Jessie Williams

Association for Research in Vision and Ophthalmology

Keeping Nerve Axons On Target

Neurons constituting the optic nerve wire up to the brain in a highly dynamic way. Cell bodies in the developing retina sprout processes, called axons, which extend toward visual centers in the brain, lured by attractive cues and making U-turns when they take the wrong path. How they find targets so accurately is a central question of neuroscience today.

Using the mouse visual system, a team of Salk Institute for Biological Studies investigators led by Dennis O’Leary, Ph.D., identified an unanticipated factor that helps keep retinal axons from going astray. They report in the Sept. 11 issue of Neuron that p75, a protein previously known to regulate whether neurons live or die, leads a double life as an axon guidance protein.

“Historically, we thought that factors that mediate cell survival and those controlling axon guidance were part of two separate processes,” says O’Leary, a professor in the Molecular Neurobiology Laboratory, “But in this study we show a direct interaction between these two systems.”

Collaborating with Kuo-Fen Lee, Ph.D., professor in the Clayton Foundation Laboratories for Peptide Biology, the O’Leary team observed a defect in mice genetically engineered to lack p75. Through their synaptic connections, retinal axons develop a two-dimensional map of the retina in their targets in the brain. In the mice lacking p75, retinal axons stopped short of their final target and formed a map that was shifted forward to the superior colliculus, a major visual center in the brain.

Such a defect in p75-null mice was puzzling: researchers have studied p75 for decades and found it associated with activities as varied as neuronal growth, survival, and degeneration. Axonal migration was not among them.

Todd McLaughlin, Ph.D., a senior research associate in the lab and co-first author, says that insight came in a eureka moment: “We realized that what we were observing in these mice was similar to what would happen if you deleted a gene called ephrin-A from the retina.”

Unlike p75, ephrin-A was a well-characterized sender and receiver of axon guidance signals, but it lacked appendages normally seen on proteins controlling axon migration. p75, however, displayed those elements, suggesting that the proteins could pair up – one receiving the migration signal and the other transmitting it.

The research team then turned to biochemical analyses and with the added expertise of Tsung Song, a research associate in Dr. Lee’s lab, obtained evidence that supported this hypothesis. The group found that ephrin-A and p75 complexes in axonal membranes and showed that when activated they could generate the signals required to guide axons and develop their map in the brain.

But the clincher was the “stripe assay,” a classical screen for guidance molecules that repel growing axons. In it, an immature neuron is placed on a microscopic running track, just as it starts to develop an axon. When flanking lanes are carpeted with repellant factors, the sprouting axon bursts from the block but remains in its lane like a well-coached runner, avoiding neighboring tracks.

Constructing tracks made from the repulsive factor sensed by ephrin-A, the researchers confirmed that axons from normal retinal neurons stayed in their lanes when flanked by the repellant. But neurons from mice lacking p75 were unreceptive to repulsive cues: when placed on the track their axons meandered all over the field, crossing lanes and running down repellant-covered stripes.

Why retinal neurons missed the target in the p75-minus mice became clear: they lacked the cellular machinery to respond to critical repellant signals encountered in the brain and stopped migrating prematurely.

Among its myriad functions, p75’s new role is a critical one. “Repulsion is probably the dominant force in axon guidance and a stronger influence than attraction,” explains McLaughlin, noting that providing axons with a lot of options is not the way to build a brain. “Attraction is like finding the best seat in an empty movie theater, but repulsion is like picking the lone empty seat in a full theater.”

“We have shown that ephrin-A cannot transduce an intracellular signal by itself and instead requires the co-receptor p75,” summarizes Yoo-Shick Lim, Ph.D., a postdoctoral fellow in the O’Leary lab and co-first author. “This interaction could operate in numerous events in neural development.”

O’Leary believes that identifying mechanisms underlying developmental events is fundamental to understanding the basis of any biological disorder. “These studies establish that two distinct molecular systems, neurotrophins and axon guidance, both critical for neural development directly collaborate to develop neural connectivity.

Findings such as these lend critical insight into how one might repair damage to the nervous system due to genetic defects, tumors or wounds to the brain or spinal cord,” he says. “We hope one day to be able to repair these defects and get cells to form functional connections again.”

Tsung-Chang Sung, Ph.D., of the Lee lab, and Alicia Santiago, Ph.D., formerly of the O’Leary lab, also contributed to the study. Salk professor Tony Hunter and Sourav Ghosh, a former postdoctoral fellow in the Hunter lab, helped with preliminary biochemical experiments. Funding was from a grant from the National Eye Institute and from the Joseph Alexander Foundation.

The Salk Institute for Biological Studies in La Jolla, California, is an independent nonprofit organization dedicated to fundamental discoveries in the life sciences, the improvement of human health and the training of future generations of researchers. Jonas Salk, M.D., whose polio vaccine all but eradicated the crippling disease poliomyelitis in 1955, opened the Institute in 1965 with a gift of land from the City of San Diego and the financial support of the March of Dimes.

Source: Gina Kirchweger

Salk Institute

Obese Women May Be Less Likely To Develop Glaucoma

Obesity may be associated with higher eye pressure and a decreased risk of open-angle glaucoma in women but not men, according to a report posted online today that will appear in the May issue of Archives of Ophthalmology, one of the JAMA/Archives journals.

“Open-angle glaucoma is a chronic eye disease characterized by glaucomatous optic neuropathy and corresponding glaucomatous visual field loss,” the authors write as background information in the article. Previous research has identified several risk factors for open-angle glaucoma, including intraocular pressure (pressure within the eye), age, sex, myopia (nearsightedness) and ethnicity.

Wishal D. Ramdas, M.D., M.Sc., of the Erasmus Medical Center, Rotterdam, the Netherlands, and colleagues examined data from 3,939 participants in the Rotterdam Study. This population-based study included participants 55 years of age and older living in a suburb of Rotterdam, the Netherlands, who did not have open-angle glaucoma when the study began between 1991 and 1993.

Over an average of 9.7 years of follow-up, 108 participants (2.7 percent) developed open-angle glaucoma. Those who developed the condition were significantly older, more often had high myopia (severe nearsightedness) and were more often male, compared with those who did not. No statistically significant effect of socioeconomic status, smoking or alcohol intake was found on the development of open-angle glaucoma.

Among women, there was a significant association between increased body mass index and intraocular pressure. However, each one-unit increase in body mass index was associated with a 7 percent decreased risk of developing open-angle glaucoma. These associations were not present in men.

Excess fat tissue could place increasing pressure on the eye sockets, thereby increasing pressure within the eye, the authors note. The higher intraocular pressure among obese women should have resulted in an increased risk for glaucoma. “However, this effect was not observed and thus the multivariate analysis yielded a protective effect of body mass index on open-angle glaucoma incidence in women,” they write. “Another explanation might be that high estrogen levels and hormone therapy might be protective to open-angle glaucoma, and obesity seems to be positively related with postmenopausal plasma estrogen levels.”

“Obesity appears to be associated with a higher intraocular pressure and a lower risk of developing open-angle glaucoma,” the authors conclude. “These associations were only present in women. Other lifestyle-related factors, such as socioeconomic status, smoking and alcohol consumption, were not associated with open-angle glaucoma.”

Archives of Opthalmology Published online February 14, 2011.doi:10.1001/archophthalmol.2010.373

Archives of Opthalmology

Eye Infection Epidemic Traced To Reduced Antifungal Properties Of Contact Lens Solution In High Temperatures

According to a study published in the November issue of Archives
of Ophthalmology, a contact lens solution that was implicated
in an epidemic of the eye infection Fusarium
keratitis between 2004 and 2006 was likely due to a reduction in the
solution’s antifungal activity because of exposure to prolonged
temperature increase.

In August 2004, Bausch & Lomb
introduced the product ReNu with MoistureLoc, a contact lens
solution that contains a unique antimicrobial agent. The solution was
associated with cases of Fusarium
keratitis, according to
U.S. government reports, since March 2006. Eventually there were 154
confirmed cases identified in the United States of this condition
characterized by inflammation of the cornea (keratitis). “Bausch
Lomb investigators acknowledged that all original cases appear to be
related to ReNu with MoistureLoc produced in their Greenville, S.C.,
plant.” write John D. Bullock, M.D., M.P.H., M.Sc. (Wright State
University Boonshoft School of Medicine, Dayton, Ohio) and colleagues.

Food and Drug Administration (FDA) inspected the Greenville facility in
2006 and cited Bausch & Lomb for poorly controlling temperature
the production, storage and transport of products from this plant.
Bullock and colleagues further studied the effects of temperature on
the growth of the Fusarium fungus by analyzing five
solutions in addition to ReNu with MoistureLoc. The researchers explain
that, “Two bottles of each solution were separately stored at room
temperature and 60 degrees Celsius [140 degrees Fahrenheit] for four
weeks, serially diluted and then tested for their ability to inhibit
growth of 11 Fusarium isolates (seven of which were
associated with the keratitis epidemic).”

with MoistureLoc showed the greatest decline in anti-fungal activity
after the 60-degree storage period, while Clear Care and ReNu MultiPlus
demonstrated the smallest decline. The authors also specifically
analyzed the strains of Fusarium that were linked
to the
keratitis epidemic. The found that when stored at room
temperature, ReNu with MoistureLoc allowed fungal growth in
27 of
84 different blends of isolates grown in different solutions
at different levels of dilution. When stored at 140 degrees Farenheit,
the solution allowed fungal growth in 67 of 84 of these combinations.

precise temperature, duration of exposure to elevated temperature and
extent of temperature fluctuation that may diminish the antimicrobial
activity of a particular contact lens solution is not known, and thus,
additional studies may be warranted. However, our findings, coupled
with the FDA reports of Bausch & Lomb’s failure to regulate the
storage and transport temperatures of the products manufactured in
their Greenville plant, may be significant,” conclude Bullock and

“Knowledge of the potential loss of antimicrobial
activity of contact lens solutions and other pharmaceutical products
when exposed to higher temperatures and the risk of such exposure when
storing and transporting those products may help prevent such epidemics
in the future.”

Temperature Instability of ReNu With MoistureLoc: A New Theory
to Explain the Worldwide Fusarium Keratitis Epidemic of 2004-2006
John D. Bullock; Ronald E. Warwar; B. Laurel Elder; William I. Northern
Archives of Ophthalmology (2008).
126[11]: pp. 1493-1498.
Here to View Abstract

Experts At Leading Vision Health Care Organization Offer 5 Summer Eye Safety Tips

As summer vacations begin, experts at Lighthouse International urge everyone to take eye safety seriously and prevent damage from the sun that could be permanent. Lighthouse International, based in New York City, is the 104 year old non-profit leader in vision health.

While many people know that unprotected exposure to the sun can cause damage to the skin, unprotected sun exposure can also harm the eyes. Boaters, fishermen, golfers and people going on cruises to the Caribbean and southern ports should be especially careful.

According to Dr. Bruce P. Rosenthal OD, Chief of Low Vision Programs at Lighthouse International “Research shows that only one in six Americans wear sunglasses when they are in the sun for long periods of time, yet people who spend excessive hours in the summer sun have an increased risk in later life of developing age-related eye conditions such as macular degeneration as well as cataracts and corneal problems. Sunglasses are vital because they keep certain wavelengths of light from entering the eye. They can also reduce the amount of light entering the eye, protect against harmful UV light, decrease glare and increase contrast.”

Here are 5 eye safety tips from the experts at Lighthouse.

1. Be sure to wear proper sunglasses – sunglasses that have 400 UV protection or more. A dark lens does not necessarily have UV protection. The key characteristic to look for is an indication that the lenses absorb 99 to 100 percent of UV light, particularly UV-B. An ultraviolet-blocking coating can also be placed on any lens, regardless of the degree of tint. However, a coating does not block as much UV light as the protective lens.

2. Be sure to wear sun glasses ,especially during long hours on the beach or on the water since the water reflects and intensifies the sun.

3. To further minimize sun damage to the eyes, people of all ages –from infants to seniors — should wear hats or visors.

4. Be sure to wear eye protection that is fitted properly when playing any sport. Such protective lenses should be made of polycarbonate which can withstand high impact. Eye injuries are one of the leading causes of visual impairment in children.

5. Avoid blue tinted sun glasses – they may look cool but blue tint actually emits ultra violet light which is what you are supposed to be blocking out.

Lighthouse International

News From The Journal Of Neuroscience

1. Modeling Electrophysiological Diversity

Variations in morphology and ion-channel expression largely determine the electrophysiological properties of neurons. To investigate whether such variations are sufficient to explain the electrophysiological variability of globus pallidus neurons recorded in brain slices, Gunay et al. created more than 100,000 computer models using three realistic morphologies and variable levels of nine ionic conductances. The models’ properties (e.g., spike threshold, waveform, afterhyperpolarization, firing rate) largely replicated the variability recorded in real neurons. Most properties were influenced by multiple conductances, and most conductances influenced multiple properties. Furthermore, complex interactions between conductances produced great variability in the magnitude of the effect produced by changing a single conductance; even the sign of the effect could change, depending on the density of the other conductances in a model. Impressively, the authors validated the model approach by using low doses of channel blockers to decrease conductance density in real neurons and produce the variability predicted by the model.

Cengiz G??nay, Jeremy R. Edgerton, and Dieter Jaeger

2. Neuronal Death Path

Li-ying Yu, Mart Saarma, and Urmas Arum?´┐Że

Programmed cell death pathways are generally divided into two broad categories: the intrinsic pathway, in which cellular stress (e.g., oxidative stress) leads to release of cytochrome c from mitochondria, which leads to activation of caspase-9, which activates effector caspases that degrade cellular proteins; and the extrinsic pathway, in which extracellular ligands bind to death receptors, which activate Fas-activated death domain (FADD) protein, which leads to activation of caspase-8, which activates effector caspases. This week, Yu et al. describe the apoptosis pathway activated by withdrawal of GDNF and BDNF from cultured midbrain dopaminergic neurons. The normal intrinsic pathway was not involved, because cytochrome c was not released from mitochondria. Nonetheless, caspase-9 was involved. Death-receptor pathways were also involved, because blocking FADD or caspase-8 prevented apoptosis. Interestingly, this apoptosis pathway is different than that induced by withdrawal of GDNF from sympathetic neurons.

3. Receptive Field Properties in Mouse Visual Cortex

Cristopher M. Niell and Michael P. Stryker

Niell and Stryker have performed a broad quantitative study of the receptive field properties of neurons in mouse visual cortex and classified the neurons based on laminar position and waveform (narrow spiking vs broad spiking, which are thought to correspond to inhibitory and excitatory neurons, respectively). Despite the poor visual acuity and lack of cortical columnar organization in mice, mouse visual cortical neurons have many of the properties seen in other species, including orientation and spatial-frequency tuning, simple and complex responses, and contrast-invariant tuning. The results provide information about the optimal stimulus parameters to use in future studies of mouse visual processing, and most importantly, they open the door to using mouse genetic strategies such as targeted gene disruption and exogenous gene expression to investigate how the cortex generates well-established sensory response properties.

4. Unexpected Effects of Dopamine Withdrawal and Replacement

Li Liang, Maholn R. Delong, and Stella Papa

A prominent model of Parkinson’s disease (PD) posits that chronic dopamine depletion causes opposite effects on striatal medium spiny neurons of the direct (striatonigral) and indirect (striatopallidal) pathways. Specifically, striatonigral neurons (~50% of the population) are thought to express primarily D1 receptors and be less excitable in PD, whereas striatopallidal neurons are thought to express primarily D2 receptors and be more excitable in PD. Moreover, L-DOPA is thought to reverse PD symptoms by reversing these changes in excitability. Experiments reported by Liang et al. contradict this model. The authors recorded individual striatal neurons in parkinsonian monkeys before and after administering L-DOPA. Contrary to expectations, all parkinsonian neurons had a higher firing rate than previously reported for striatal neurons in normal monkeys. Furthermore, L-DOPA further increased firing rate in 64% of neurons. Thus, excitability appears to be increased in neurons of both pathways, and L-DOPA actions do not simply reverse this effect.

Please click here for the current table of contents.

Source: Sara Harris

Society for Neuroscience

Presto! Fast Color-changing Material May Lead To Improved Sunglasses – Journal Of The American Chemical Society

Researchers in Japan are reporting development of a new so-called “photochromic” material that changes color thousands of times faster than conventional materials when exposed to light. The development could lead to a wide range of new products including improved sunglasses, more powerful computers, dynamic holograms, and better medicines, the researchers say. Their report appears in the Journal of the American Chemical Society, a weekly publication.

In the new study, Jiro Abe and colleagues note that photochromic materials are most familiar as the invisible layers found in the lenses of many high-end sunglasses, which change color when exposed to sunlight. For years, researchers have explored the possibility of using these unusual materials for optical data storage in computers and as “molecular switches” for more controlled drug delivery. Conventional photochromic materials, however, tend to be relatively slow-acting (tens of seconds to hours) and unstable, which prevents their use for many advanced applications, the scientists say.

The scientists describe development of a unique photochromic material that shows instantaneous coloration upon exposure to ultraviolet light and its disappearance within tens of milliseconds when the light is turned off. The decoloration speed is thousands of times faster than conventional materials. The material is also more stable and longer-lasting, they note. In laboratory studies, the scientists showed that the new material could instantly change from colorless to blue in both solid form and in solution when they exposed the molecules to ultraviolet light, and quickly back to colorless when the light is turned off. The development opens the door to futuristic technologies “with unprecedented switching speeds and remarkable stabilities,” the article notes.

Click for article

American Chemical Society

Melanoma Of The Eye Not Linked To Mobile Phone Use

Mobile phone use is not associated with the risk of melanoma of the eye, researchers report in the January 13 online issue of the Journal of the National Cancer Institute.

Although there is no direct link between exposure to radio waves and DNA damage, which can lead to cancer, studies have examined the possibility of an association between mobile phone use and melanoma of the eye, also called uveal melanoma.

In the current study, Andreas Stang, M.D., of the Martin-Luther-University of Halle-Wittenberg in Germany, and colleagues examined the association between phone use and risk of uveal melanoma in 459 patients and 1,194 control subjects. Control subjects were drawn from the general population, from ophthalmology clinics, and from siblings of the patients. The investigators grouped study participants according to amount of time spent on the phone, as never users, sporadic users and regular users.

There was no statistically significant association between mobile phone use of up to about 10 years and uveal melanoma risk.

“In conclusion, we observed no overall increased risk of uveal melanoma among regular mobile phone users or users of radio sets in Germany, where digital mobile phone technology was introduced in the early 1990s,” the authors write.


Stang A, et al. Mobile Phone Use and Risk of Uveal Melanoma: Results of the Risk Factors for Uveal Melanoma Case-Control Study. J Natl Cancer Inst


The Journal of the National Cancer Institute Institute is published by Oxford University Press and is not affiliated with the National Cancer Institute. Visit the Journal online at jnci.oxfordjournals/.

Source: Caroline McNeil

Journal of the National Cancer Institute