Nancy Groves

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-Several mechanisms of idiopathic intracranial hypertension (IIH), acting in isolation or coupled, have been proposed. Independent observations of increased cranial cerebrospinal fluid (CSF) volumes and altered venous outflow now provide strong evidence that the previously suggested mechanisms of impaired CSF homeostasis and venous outflow co-exist in obesity-related IIH.

Previous studies suggested that subarachnoid ventricular spaces are larger in patients with IIH, but measurements are highly variable. Also, limited or inconsistent reports of the normative values of extraventricular CSF volume confound the difficulty in determining whether total intracranial CSF volume increases in IIH, said Byron L. Lam, MD, professor of ophthalmology, Bascom Palmer Eye Institute and Department of Radiology, University of Miami.

To clarify these issues, Dr. Lam and colleagues prospectively studied MRI-derived measures of total cranial, ventricular, and extraventricular CSF volumes in patients with IIH. The rationale was that if IIH is associated with decreased CSF absorption, then increased CSF volume should be expected.

The investigative team studied the MRI images of 14 newly diagnosed, untreated female patients with IIH before a diagnostic spinal tap. The comprehensive imaging consisted of high-resolution T

-weighted MRI and velocity-encoded MRI images of arterial inflow and venous outflow. The same comprehensive MRI imaging was performed on a control group of 11 healthy women of similar age and body mass index (BMI).

The patients with IIH had mild to moderate IIH, were relatively young (27 ± 9 years), had increased BMI, and had good visual acuity. Their visual fields were mildly to moderately decreased (up to –7.0 dB). Papilledema grading ranged from 1 to 4, and the opening CSF pressures ranged from 26 to 47 cm H

CSF volumetric measurements were performed using 3D T

-weighted sequences with isotropic resolution of 1 mm and segmentation of intracranial space into gray matter, white matter, and CSF. Intracranial CSF volume was the total intracranial volume minus the volume of the gray and white matter. The ventricular CSF volume was the sum of the lateral third and fourth ventricles, and the extraventricular volume was calculated as the numerical difference between the intracranial and intraventricular CSF volumes.

Although the age and BMI of the patients with IIH and controls were similar, the extraventricular CSF space was significantly greater in the patient group versus the controls, 244.1 ± 36.4 ml and 208.8 ± 26.7 ml, respectively (

“This really accounts for the increase in intracranial CSF in the patients with IIH compared with the controls,” he added.

The measurements of intracranial CSF were 263.8 ± 41.8 ml in the patient group and 227.3 ± 28.3 ml in the controls (

 < 0.017). The ventricular volume was the same between the two groups (19.7 ± 8.7 ml in the patients with IIH and 18.7 ± 6.2 ml in the controls).

Even when the data were normalized to reduce intra-individual variability, the difference in extraventricular CSF volume remained significant, Dr. Lam said.

Reporting cranial volumetric measurements, he noted that the gray matter volume in the patients with IIH was greater than in the control group (

 = 0.38), while the white matter was similar between the groups. This suggests increased interstitial fluid or blood volume, or both, Dr. Lam said. The total intracranial volume was also higher in the patient arm (

Results for the arterial and venous flow measurements showed that the total cranial blood flow was the same between groups, but the total internal jugular flow was lower in the patients with IIH (

 = 0.011), indicating increased venous outflow resistance.

Dr. Lam presented these findings at the annual meeting of the Association for Research in Vision and Ophthalmology.

Dr. Lam did not report any relevant commercial relationships.

Articles

To clarify whether total intracranial CSF volume increases in IIH, researchers prospectively studied MRI-derived measures of total cranial, ventricular, and extraventricular CSF volumes in patients with IIH and controls. Results showed that the extraventricular CSF space was significantly greater in the patient group versus the controls. The ventricular volume was the same between the two groups.

IIH mechanisms clarified

-Researchers in the United Kingdom have shown that face recognition is an issue worthy of study in patients with glaucoma. Preliminary work has suggested that certain eye movement patterns are associated with better face recognition performance in patients with central glaucomatous visual field loss.

“A lot of research in glaucoma tends to focus on clinical measures such as visual fields for detecting and monitoring the disease within a clinical environment; however, it is also important to consider how these largely numerical values translate to the person’s functioning in day-to-day activities,” said Fiona C. Glen, MA, a PhD researcher in the Department of Optometry and Visual Science, City University London, United Kingdom.

“This is going to be information that is most important to the patients. They will want to know what changes to expect in their life, when to expect them, and whether they will still be able to carry out the activities that are most important to them,” Glen said.

Impairment in face recognition ability could be significant as well as extremely distressing for a patient. Glen and colleagues at City University London, Moorfields Eye Hospital, and University College London examined whether patients with glaucoma had difficulty recognizing faces and recently published a paper in 

Investigative Ophthalmology & Visual Science

 demonstrating that patients with glaucoma and advanced visual field loss and poor contrast sensitivity were more likely to experience problems with face recognition than people of a similar age with healthy vision.

This research also showed that the type of visual field defect appeared to be important. Patients who had defects closer to fixation, in the central 10º, performed worse at face recognition. However, the researchers noticed that some of the patients were still good at the task despite advanced defects.

“We speculated that some of these patients might be doing something differently that allowed them to perform better at the task, and based on other work we had been carrying out we thought there might be reason to believe that their eye movements were different,” Glen said.

Work presented this spring at the annual meeting of the Association for Research in Vision and Ophthalmology represented the first stage in exploring that theory. In that study, Glen and colleagues recorded the eye movements of 26 patients with glaucoma and 38 age-similar controls. The movements were recorded with an Eyelink 1000 while the subjects performed the Cambridge Face Memory Test (CFMT).

The participants had visual acuity better than 6/9, underwent various visual function tests, and were in good cognitive health. The patients with glaucoma had a median 24-2 mean deviation (MD) of –7.7 dB and significant central 10º visual field defects as defined by 10-2 MD <1% normative value, all in the better eye.

“We found that some of the patients who had advanced loss in the central 10º seemed to show some sort of different eye movement behavior, and some of these patients were also performing very well at the task. However, we did not see as much of an association between eye movement and performance in the people who had normal vision,” Glen said. “It is speculative at this stage, but we believe this could indicate that some patients may use eye movements to help them adapt to their vision loss in activities like face recognition.”

In the patient group, the researchers found a significant partial correlation (controlling for age) between the percent of correctly identified faces in the CFMT and the number of saccades made per second when they first viewed a single face (r = 0.68, 

 <0.001). No significant association was found between face recognition performance and the number or size of saccades in the controls (r = 0.16, 

An interesting question for future research is whether some patients are consciously coming up with strategies such as changes in eye movement to help them manage tasks such as face recognition despite their vision defects, or whether it is an unconscious adaptation, Glen said. She added that the research group also is studying eye movement in other tasks and that some of this work is already published.

Glen did not report any relevant commercial relationships.

1. Glen FC, Crabb DP, Smith ND, Burton R, Garway-Heath DF. Do patients with glaucoma have difficulty recognizing faces? 

2. Crabb DP, Smith ND, Rauscher FG, et al. Exploring eye movements in patients with glaucoma when viewing a driving scene. 

3. Smith ND, Crabb DP, Glen FC, Burton R, Garway-Heath DF. Eye movements in patients with glaucoma when viewing images of everyday scenes. 

. 2012;1-22. DOI: 10.1163/187847612X634454.

Certain eye movement patterns seem to be associated with better face recognition performance in patients with central glaucomatous visual field loss.

Eye movement affects glaucomatous vision

 is on track for in vivo validation of  function and an 

 investigational device exemption application, according to  Joseph F. Rizzo III, MD, a neuro-ophthalmologist at Massachusetts Eye & Ear  Infirmary.

Dr. Rizzo,  who is leading the retinal prosthesis team, said that development of the  high-density wireless neurostimulator is nearly complete. Milestones expected  by late 2012 or early 2013 will include completion of bench testing and initial  preclinical testing in Yucatan mini-pigs.

Dr. Rizzo and two other members of  the development team, engineers John L. Wyatt, PhD, and Douglas B. Shire, PhD,  described progress on the implanted component of the prosthesis in a  presentation at the annual meeting of the Association for Research in Vision  and Ophthalmology. Well-designed packaging technology for the large number of  stimulating electrodes necessary to get high-quality vision is a critical step  in creating an implantable prosthesis, noted Dr. Rizzo, who initiated the  retinal implant project in 1988.

This prosthesis and others being  developed by groups worldwide are intended to restore vision lost to degenerative  retinal diseases such as age-related macular degeneration and retinitis  pigmentosa.

Providing details on the Boston  group’s work, Dr. Shire said that three progressively better versions of the  stimulator’s custom-designed, application-specific IC computer chip have been  fabricated and tested, and although one more round of modification may take  place soon, the current model should be suitable for animal trials. Dr. Shire  is a research health scientist at the Boston VA Medical Center and engineering  manager for the VA Center for Innovative Visual Rehabilitation.

The prosthesis consists of a camera  mounted on an eyeglass frame that wirelessly supplies images to an implant  containing an array of tiny stimulating electrodes. The 5 mm by 5 mm, low-power  chip decodes this information and stimulates the retinal ganglion cells, which  induces precepts that correspond to the strength and location of the stimuli.  The integrated circuit drives the electrodes with biphasic current pulses in  response to an external controller via a frequency-shift keyed radio  transmitter.

The development team recently  modified the electrode array with a coiled cable design that reduces surgical  implantation time and allows flexibility in selecting the entry point to the  subretinal space.

The wireless communication protocol  is extremely important and includes an error-detecting code, Dr. Shire said. The chip does not respond if a command is invalid and will wait for another,  valid command.

The implant also has several other built-in  safety precautions. Hardware limits prevent the total charge from exceeding  safe values and damaging the retina. Independent circuits monitor electrode  voltages between each positive and negative pulse and can determine if the  voltage is too high or too low. In addition, electrodes are shorted to ground  between pulses.

The technology for creating paths  for individual electrodes to pass through the hermetically sealed titanium case  containing the electronics is extremely important since it protects these  sensitive components from damage in the saline environment in which they are  implanted, said John L. Wyatt, PhD, professor of electrical engineering and  computer science at Massachusetts Institute of Technology. He is the head of  the MIT engineering team for the implant project.

The package contains circuitry  mounted on the internal surface of the ceramic feedthrough that contains one  conductive path for each electrode. The package is sealed by welding, and  connections to the outside are protected by a plastic header that is dimpled to  allow the package to rest against the sclera. A completed package is  approximately 11 mm in diameter and 2 mm thick.

The internal assembly requires  attachment of a circuit board containing the stimulator chip to all the signal  feedthrough pads simultaneously. On the external side, the flexible electrode  array and coil are attached by first electroplating gold onto the electrode  array and onto the ceramic disk, and then bonding the two together using a  thermosonic process.

Drs. Rizzo, Shire, and Wyatt are co-inventors of intellectual property related to the  prosthesis and own equity in Bionic Eye Technologies, a medical device company  developing novel solutions to assist the blind. Dr. Rizzo and Dr. Wyatt serve on  the company’s board, and Dr. Rizzo is an ex-officio member.

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The 256+ channel Boston subretinal prosthesis is on track for in vivo validation of function and an FDA investigational device exemption application.

Retinal prosthesis on track for further testing

Dr. Starr, who is assistant professor of ophthalmology at Weill Cornell Medical College in New York City, suggested that data showing higher prevalence of dry eye as people age may be in part related to the fact that a lot of people's disease isn't diagnosed and treated when they are younger. By the time the disease is detected later in life, it has become more severe and treatment becomes more challenging, added Dr. Starr, who is also director of the residency program and cornea fellowship program and director of refractive surgery at Weill Cornell Medical College, New York-Presbyterian Hospital. 

Although it's better to be treated at a late stage of dry eye than not treated at all, the current treatments are more effective when started earlier. This is particularly true of anti-inflammatory medications such as cyclosporine (Restasis, Allergan). 

Signs found on an eye exam, especially those outlined by the Delphi Panel report, may include both conjunctival and early corneal staining, Dr. Starr said. 

"If there's any staining whatsoever and there's no other obvious cause, more likely than not this is a [patient with] moderate dry eye [that] should be treated. If [it is] not adequately treated, [it] will probably progress to more severe dry eye in the future and [the patient will] return, likely to someone else, with more advanced signs and symptoms of dry eye disease." 

Even when the severity level is correctly identified, treatment for patients with moderate dry eye is not always as thorough as it should be, Dr. Starr said. Although doctors typically categorize the symptoms correctly, they often recommend treatment better suited to an earlier stage, such as artificial tear use alone. 

"That is really ineffective," Dr. Starr said. "The patient will feel better, at least for a brief amount of time until the drop wears off, but it does nothing to treat the underlying cause of the ocular surface disease: inflammation. Artificial tears by themselves don't really do anything to decrease inflammation." 

The international guidelines created by the Delphi Panel recommend use of an anti-inflammatory medication as early as level 2 (early moderate) on a severity scale of 1 to 4. Along with topical cyclosporine, the panel also recommends short-term topical steroids for level 2 disease. Of note, punctal plugs are not recommended until level 3 severity. 

Failure to follow these recommendations by treating the symptoms of moderate dry eye only with artificial tears is likely contributing to the progression of disease to higher severity levels. In moderate and more advanced disease, it is perfectly appropriate to use artificial tears as an adjunct to the primary anti-inflammatory treatment, Dr. Starr said. 

Careful counseling and managing patient expectations are also critical in moderate dry eye because the only FDA-approved anti-inflammatory treatment for dry eye, cyclosporine, doesn't reach clinical significance as quickly as one might hope. Often, Dr. Starr said, patients try it for as little as a few days or a few weeks before concluding that it doesn't work, and they give up because of the lack of obvious clinical improvement. 

Doctors should explain to patients that it may be about 2 to 3 months before a clinically relevant effect is apparent and 6 months before the benefit is significant, with further improvement through ongoing use.

Many ophthalmologists may be dropping the ball when treating moderate dry eye, which could result in progression to more severe stages of disease.

Author | Nancy Groves

Articles

IIH mechanisms clarified

Eye movement affects glaucomatous vision

Retinal prosthesis on track for further testing

Earlier intervention more effective