Caffeine May Help Prevent Cataracts
As it turns out, that dependable cup o’ Joe may not only help open your eyes each morning, it may keep them seeing more clearly over time. Tea and coffee alkaloids may have an anticataractogenic effect on the lens of the eye, according to Shambhu D. Varma, PhD, professor of ophthalmology and visual sciences at the University of Maryland in Baltimore, and research partner Kavita R. Hegde, MD, PhD, assistant professor of ophthalmology and visual sciences there.
The researchers had previously shown that compounds such as bioflavonoids and pyruvate are effective in significantly delaying the onset of cataract formation in experimental animals with diabetes. In recent mouse studies, they explored the usefulness of caffeine in preventing cataracts. Ultraviolet light is a well-established factor in cataractogenesis, as it initiates photochemical generation of free radicals.
“We thought there must be some way to prevent this UV damage with free radical scavengers because we’d previously observed the inhibitory effects of such scavengers against formation of cataracts associated with diabetes, aging and galactosemia,” said Dr. Varma. Because caffeine is a free radical scavenger and the oxidative product of caffeine is methylated uric acid—also a free radical scavenger—the researchers thought caffeine might be a more effective and reliable molecule than ones tested previously.
Drs. Varma and Hegde studied this problem by incubating isolated mice lenses under UV 302 nm for five hours in the absence or presence of caffeine (5 millimoles).1
The researchers first identified lens damage from UV exposure by studying the lens metabolism. “One of the best indices of tissue metabolism is its ability to produce ATP,” said Dr. Varma. He and Dr. Hegde found that not only did UV light depress ATP production but also that caffeine substantially abolished this impact.
That UV light also induces oxidative stress was reflected by the loss of a tripeptide called glutathione (GSH), a natural antioxidant normally present in the lens at very high concentrations, said Dr. Varma. GSH was also better maintained in the presence of caffeine.
The researchers also tested one of the most important physiological parameters of the lens—the transport of potassium from outside the lens to the inside, a process dependent upon the pump enzyme sodium-potassium ATPase. Under UV radiation or in the presence of other toxic agents, said Dr. Varma, the pump enzyme gets inhibited. “When this happens, the entire electrolyte composition of the intracellular milieu is disturbed,” said Dr. Varma. “This results in many unwanted chemical reactions that have a bearing on the formation of cataracts.”
Using rubidium as a surrogate for potassium, the researchers confirmed the deleterious impact of UV light on this pump as well as caffeine’s ability to counteract it.
Finally, the researchers assessed the lenses for transparency by evaluating their ability to transmit light. “Lenses incubated in a medium containing caffeine were much more transparent as compared with those incubated without caffeine.”
Although orally ingested tea and coffee alkaloids are absorbed through the gastrointestinal tract and penetrate the blood-aqueous barrier, Drs. Varma and Hegde hope instead to develop eyedrops that individuals can apply directly—once clinical trials are successfully completed.
1 Varma, S. D. and K. R. Hegde. Poster #D852, Usefulness of caffeine against UV-B induced damage to lens and cataract formation. Presented at the Association for Research in Vision and Ophthalmology, Monday, April 28, 2008.
Risk of Glaucoma in Early Congenital Cataract Surgery
Ophthalmologists should be aware of the risk of complications associated with cataract surgery on patients who are younger than 9 months of age,” said Brigitte Haargaard, MD, PhD, senior ophthalmology resident at Copenhagen University Hospital and epidemiology researcher at the Statens Serum Institut in Copenhagen. “These patients should be monitored regularly for life.”
Glaucoma is one of the most severe complications resulting from surgery for congenital cataract. Some researchers suggest that the occurrence is as high as 59 percent, but other estimates are as low as 8 percent.
A number of factors have been associated with glaucoma development in these patients. Researchers examined the effect of cataract etiology, surgical technique, surgery for secondary cataract, cataract morphology, other ocular anomalies, age at surgery and time since surgery. The possibility that primary intraocular lens implantation may be protective against glaucoma was also investigated.
Extending their research from a previous epidemiological study, Dr. Haargaard and her colleagues reviewed the medical charts of all children in Denmark under the age of 17 who had undergone surgery for pediatric cataract between 1977 and 2001.1
Of the 595 patients, or 946 eyes, included in the study, 48 patients, or 72 eyes, developed glaucoma subsequent to pediatric cataract surgery. Researchers found that surgery performed before 9 months of age was associated with a 7.2-fold increase in risk of glaucoma compared with surgery that was performed at 9 months of age or later. “After adjusting for age at the time of surgery, no other risk factor appeared to be important,” said Dr. Haargaard.
Glaucoma was also identified more than 10 years after cataract surgery in 31.9 percent of the patients who underwent surgery before the age of 9 months. In contrast, patients who underwent surgery at 9 months of age or older only had a 4.1 percent rate of glaucoma occurrence.
“Surgery cannot be avoided in these children, especially if they are born with dense bilateral congenital cataract. The surgery should be performed very early—within the first 8 to 10 weeks of life to achieve good visual acuity—and should not be postponed due to the risk of amblyopia and nystagmus. Ophthalmologists simply need to know that there is a high risk that these patients will develop postoperative glaucoma. Careful and continuous observation is mandatory,” said Dr. Haargaard.
Monitoring children who are 2 years of age and younger can be difficult if intraocular pressure is the sole measurement, particularly when other characteristics may better identify the first signs of glaucoma.
Dr. Haargaard suggested that “corneal diameter and axial length, as well as evaluating the optic disc for any increase in excavation, are important measures that can identify glaucoma in very young children and should be used in addition to IOP data.”
1 Invest Ophthalmol Vis Sci 2008;49(5):1791–1796.
Cyclosporine Improves Corneal Sensitivity
Nerve regeneration remains a Holy Grail for all of medicine, and ophthalmic researchers may be a step closer to this elusive goal.
Gholam A. Peyman, MD, clinical professor of ophthalmology at the University of Arizona and Arizona State University, and colleagues conducted a randomized pilot study showing that cyclosporine 0.05 percent (Restasis) can significantly improve corneal sensitivity at three months post-LASIK. These findings suggest topical cyclosporine promotes enhanced corneal nerve regeneration, Dr. Peyman said.
The study included 44 eyes of 22 patients. One eye of each patient was randomly assigned to receive one cyclosporine drop in the morning and one in the evening for three months following LASIK surgery.
Using the Cochet-Bonnet esthesiometer, the investigators measured corneal sensitivity in four areas outside and five areas inside the LASIK flap.1
“Our results showed that after three months of treatment with topical cyclosporine, the points within the flap area had significantly greater corneal sensitivity than the fellow, untreated eye,” Dr. Peyman said, “with the most central cornea area showing the most dramatic difference.”
He said the findings were a surprise. “It was quite striking to find such differences in the treated versus untreated eye with such a small sample size,” Dr. Peyman noted.
Dr. Peyman also has studied nerve regeneration, noting that immunosuppressants have previously shown a neuroprotective effect in traumatic brain injury and sciatic nerve injury in animals.
He hypothesized the rapid corneal nerve recovery with topical cyclosporine may be due to the fact that the corneal nerve cells are peripheral nerves with nonmyelinated nerve fibers—in contrast to central nervous system brain and spine nerve cells, which are myelinated. “However, we still need more research into why this topical immunosuppressant is effective in regenerating nonmyelinated nerve fibers of the cornea,” he said.
In the meantime, coauthor Donald R. Sanders, MD, PhD, director, Center for Clinical Research, a consulting company in Elmhurst, Ill., said, “This approach can enhance the safety of LASIK by helping the corneal nerves heal faster. If the eye can’t feel anything after surgery, it is more prone to injury.”
—Lori Baker Schena
1 J Refract Surg 2008;24:337–343.
Dr. Peyman has a patent pending on neuronal regeneration using cyclosporine. Neither Dr. Peyman nor Sanders reports an interest in Allergan.
Activity and Myopia
Is there a significant relationship between the level of physical activity of “20-somethings” and the development and progression of myopia? A two-year longitudinal cohort study of medical students by a trio of Danish research ophthalmol- ogists says that there is.1
While the influence of physical activity on the development and progression of myopia in children has been studied, scant data exist on this issue in young adults. “Previous studies have shown that university students, particularly medical students, are at risk of developing adult-onset myopia during their university studies, perhaps as a result of extensive studying” said Nina Jacobsen, MD, PhD, of the Kennedy Center, National Eye Clinic in Hellerup, Denmark. “We wanted to test whether physical activity might have a protective effect on the development of myopia in medical students.”
A total of 151 Caucasian first-year medical students from the University of Copenhagen completed the study, initiated in 2005, with measurement confirmations repeated in 2007. Baseline exams included an extensive eye examination, an oral questionnaire and to measure physical fitness, cycle ergometer tests.
The results confirm that intensive studying is, indeed, a risk factor of myopia and that myopic development or progression is more likely in medical students in their early 20s than in their late 20s.
“The most interesting issue from the study is that our results indicate that the development or progression of myopia, which many university students face, can be reduced or avoided by physical activity,” said Dr. Jacobsen. “Our study shows that the average amount of time spent on physical activity is just one hour per day . . . and suggests that increasing this amount of time by another hour per day can prevent the average myopisation that the students experience.”
Dr. Jacobsen notes, however, that this study is observational, and therefore, “to establish a true cause-and-effect relation between myopia and physical activity, an intervention-study will need to be done.”
1 Invest Ophthalmol Vis Sci 2008;49(4):1322–1327.
Rehab Pays Off for Low Vision Patients
Low vision rehabilitation, long thought of as “better than nothing,” is actually better than that. It works. What’s more, doing nothing leads to decline in everyday functioning.
That’s the conclusion of the Veterans Affairs Low Vision Intervention Trial (LOVIT), a multicenter randomized controlled study that evaluated the effectiveness of a low vision rehabilitation program among veterans at outpatient clinics in Illinois and North Carolina.1
The LOVIT showed that a program of assessment, counseling, eccentric viewing training (training to use areas of the healthy retina) and instruction in the use of everything from closed circuit TVs and pocket magnifiers to glare control filters and talking watches can restore functional ability to the patient whose world has been shutting down.
The treatment group thrived. After receiving four weeks of the kind of interdisciplinary services advocated by the Academy, the treatment group exhibited a gain in overall visual ability equal to a 16-line improvement in ETDRS visual acuity.
Without intervention, patients got worse, prompting LOVIT researchers to recommend that doctors offer rehabilitation as soon as possible. The everyday functional abilities of the wait-list control group declined over four months, the average waiting time for low vision services.
Treatment effect was self-reported by phone. Participants rated reading ability, mobility, visual information processing and visual guided motor behavior, on a scale of “not difficult” to “impossible.”
Results were quantified in logits, or log odds ratios, which correspond to a valid and sensitive analytical measure of self-reported outcomes. More familiarly, the reported 2.06-logit improvement in reading ability corresponds, roughly, to a 16-line improvement in ETDRS visual acuity. The control group’s 0.37-logit loss approximates a 3-line loss.
These acuity numbers should not be taken literally, warned Robert W. Massof, PhD, a LOVIT researcher and professor of ophthalmology and neuroscience at Wilmer Eye Institute. “But they will help you understand the magnitude of the effect.” He added that while LOVIT demonstrates a huge effect, “people are not getting better than normal.”
Future studies will have to address the persistence of treatment effect, the authors noted. And still unknown is which treatment component, or combination of components, is primarily responsible for the observed effect.
In the meantime, Mary Lou Jackson, MD, director of Vision Rehabilitation at Massachusetts Eye and Ear Infirmary, said, “The LOVIT study provides ophthalmologists, who are often the gatekeepers for patients who can benefit from vision rehabilitation, the evidence to support referring patients to low vision services.”
She added that the number of low vision programs continues to grow in academic ophthalmology settings. “It is hoped,” she said, “that when communicating with patients with vision loss, future generations of ophthalmologists will not need the phrase, ‘Nothing more can be done.’”
1 Stelmack, J. A. et al. Arch Ophthalmol 2008;126(5):608–617.
EyeNet thanks Steven I. Rosenfeld, MD, FACS, Brian Francis, MD, William B. Trattler, MD, and Rebecca K. Morgan, MD, for their help with this issue’s News in Review.