Volume 4, Number 5
Monday, February 2, 2004



In this issue: (click heading to view article)
Open-angle Glaucoma and Systemic Thyroid Disease in an Older Population
Tamoxifen Use and Visual Sensitivity
Reflectance of Single Cones in the Human Eye
Macular Hole Surgery and Cytotoxicity of Indocyanine Green on RPE
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Open-angle Glaucoma and Systemic Thyroid Disease in an Older Population

A population-based study by the University of Sydney’s Department of Ophthalmology suggests that thyroid disease, indicated by current thyroxine use or past thyroid surgery, could be independently related to open-angle glaucoma (OAG).

Researchers used results of the Blue Mountains Eye Study, which examined 3,654 persons aged 49 to 97. Interviewers collected self-reported histories of diagnosis and treatment for thyroid disease. Eye examinations included applanation tonometry, stereoscopic optic disc photography and automated perimetry. Clinicians diagnosed OAG from the presence of matching typical glaucomatous field changes and optic disc cupping, independent of intraocular pressure. Associations between thyroid disease (history and treatment) and OAG were assessed in a multivariate model.

Of 324 participants (8.9 percent) reporting history of thyroid disease, 147 (4 percent) were currently using thyroxine. Although researchers could not accurately categorize the thyroid disorder for all cases, current use of thyroxine suggested a prior hypothyroid state. All thyroid disease subgroups affected women more frequently than men. OAG was diagnosed in 108 subjects (3 percent) and was more frequent in those reporting past thyroid disease (4.6 vs. 2.8 percent). This relationship was not statistically significant after adjusting for potential confounders. OAG was significantly more frequent, however, in subjects reporting current thyroxine use (6.8 vs. 2.8 percent) or history of thyroid surgery (6.5 vs. 2.8 percent).
SOURCE: Lee AJ, Rochtchina E, Wang JJ, et al. Open-angle glaucoma and systemic thyroid disease in an older population: the Blue Mountains Eye Study. Eye 2004;Jan 9 (Epub ahead of print).
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Tamoxifen Use and Visual Sensitivity

Standard dosages of tamoxifen can affect short wavelength automated perimetry (SWAP) visual fields and may affect some types of visual pathways preferentially or selectively, according to a study by Oregon Health & Science University researchers.

Estrogen receptors have been reported to be present in the retina, and the selective estrogen receptor modulator tamoxifen has been reported to affect color vision. Researchers aimed, therefore, to determine whether standard doses of tamoxifen affect visual sensitivities mediated via short wavelength sensitive (SWS) cones. They measured two types of visual fields for middle-aged women who were being treated with 20 mg of tamoxifen daily as adjuvant therapy for early-stage breast cancer. Visual fields were measured using SWAP and frequency doubling perimetry (FDP). For SWAP, 24-2 visual fields were analyzed. No subjects had tamoxifen retinopathy or other eye disease. For each type of visual field, mean deviations were assessed as a function of the duration of tamoxifen use, using a cross-sectional design. The difference between the two types of mean deviations was computed after standardization of each type of mean deviation separately, and this difference itself was evaluated as a function of the duration of tamoxifen use. Researchers further evaluated duration-dependent changes for SWAP as a function of eccentricity within the visual field, and they compared visual field data with foveal data obtained psychophysically.

Results showed that SWAP sensitivities depended on the duration of tamoxifen use. Subjects who used tamoxifen for two years or less were significantly more likely to have high mean deviations than subjects who had longer use. The difference between the standardized SWAP and FDP mean deviations likewise was significantly related to duration of use, whereas duration-of-use effects for FDP itself were reduced or absent. Although the duration of use effect observed for SWAP was strongest in the peripheral portion of the visual field, there was evidence of changes in SWS cone-mediated vision even at the fovea.

According to authors of the study, the fact that the effects of tamoxifen are not equivalent for SWAP and FDP indicates that tamoxifen affects some types of visual pathways preferentially or selectively. SWS cone pathways in particular, are affected. SWAP appears able to reveal effects of tamoxifen occurring years before completion of the standard five-year regimen of use.

SOURCES: Eisner A, Austin DF, Samples JR. Short wavelength automated perimetry and tamoxifen use. Br J Ophthalmol 2004;88:125-30.
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Reflectance of Single Cones in the Human Eye

Researchers at the Department of Biomedical Engineering and the Center for Visual Science at New York’s University of Rochester conducted a study in which they imaged individual cones in the living human eye using the Rochester adaptive optics ophthalmoscope. In all eyes, large differences were evident between the reflectance of different cones, even when all the photopigment was bleached. To help understand what produces this spatial variation, the investigators explored whether it is a static or a dynamic property of the cone mosaic.

Fully bleached cone images were acquired in three eyes with an adaptive optics system. Investigators collected images over a 10-minute period approximately every hour for 24 hours. They measured temporal variation in cone directionality in one eye. Finally, they compared experimental data on the temporal variation of absorption with findings in various models of reflectance.

Results suggested that cone reflectance changes over time appear to be independent from cone to cone. These temporal changes were present in all three cone classes. The spatiotemporal variation in cone reflectance is not caused by the spatiotemporal variation in the optical axes of cones. Along with the modeling results, this suggests that changes in the reflectance affect the light that passes through photopigment in the receptors rather than the stray light, and that the changes are related to the outer segment-retinal pigment epithelium interface. The authors of the study conclude that the reflectance of individual cones is a dynamic property of the mosaic, and that changes are evident over periods of minutes as well as many hours. The cause of the variation is not known, but authors speculate that it may be related to the process of disc shedding in receptors.

SOURCE: Pallikaris A, Williams DR, Hofer H. The reflectance of single cones in the living human eye. Invest Ophthalmol Vis Sci 2003;44:4580-92.
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Macular Hole Surgery and Cytotoxicity of Indocyanine Green on RPE

A study conducted by Taiwan’s Chang Gung Memorial Hospital evaluated the potential cytotoxic effects of indocyanine green (ICG) on cultured human retinal pigment epithelium (RPE) and the resultant implications for macular hole surgery.

Human RPE cells were exposed to ICG in concentrations from 0.001 to 5 mg/mL. The exposure duration ranged from five minutes to three hours. Researchers used light microscopy, MTS viability assay and calcein AM–ethidium homodimer 1 staining to evaluate the cytotoxic effects of ICG.

The RPE cells incubated with up to 5 mg/mL of ICG for five minutes or less exhibited no morphologic change and no significant decrease in dehydrogenase activity. When RPE cells were exposed to 5 mg/mL of ICG for 10 minutes, 1 mg/mL of ICG for 20 minutes, or 0.01 mg/mL of ICG for three hours, cell morphologic features were altered, mitochondrial dehydrogenase activity decreased, and some cells were necrotic.

Results suggest that ICG may cause cytotoxicity in human RPE in a dose- and time-dependent manner. Because ICG may be retained in the vitreous cavity for a lengthy period, the authors recommend a thorough washout of ICG during macular hole surgery.

SOURCE: Ho J-D, Tsai RJ-F, Chen S-N, et al. Cytotoxicity of indocyanine green on retinal pigment epithelium: implications for macular hole surgery. Arch Ophthalmol 2003;121:1423-9.
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BRIEFLY
  • ALCON FILES NDA FOR NEW GLAUCOMA TREATMENT, ANNOUNCES PRELIMINARY TRIAL RESULTS. Alcon has announced that the FDA has accepted the filing of its new drug application for a new glaucoma treatment, Travoprost 0.004% + Timolol 0.5% Fixed Combination (TTFC). The company also presented preliminary six-week data from three of its ongoing Phase III clinical trials on the drug at the recent Royal Hawaiian Eye Meeting. The data from one of these studies demonstrated that TTFC reduced intraocular pressure (IOP) by up to 12 mmHg. TTFC reduced IOP 2 mmHg more than travoprost 0.004% alone at the 8:00 a.m. time point; at the 10:00 a.m. and 4:00 p.m. time points, TTFC reduced IOP between 1 and 2 mmHg more than travoprost 0.004% alone. Alcon also presented preliminary data from two other Phase III clinical trials, which compared the IOP-lowering effect of TTFC to concomitant therapy of travoprost 0.004% dosed in the evening plus timolol 0.5% dosed in the morning. TTFC was not statistically different from concomitant therapy at all the 8:00 a.m. time points and at most, but not all, of the other measured time points. Data from all three trials demonstrated that TTFC has a safety profile comparable to the two single agents dosed concomitantly and that it was safe and well tolerated in the patients who participated in the trials.
  • TOPCON’S PATIENT-DRIVEN AUTOMATED REFRACTOR APPROVED BY FDA. Topcon Medical Systems, Inc. recently announced that its BV-1000 patient-driven automated refraction system has received FDA Approval. The BV-1000 combines an objective simultaneous binocular autorefractor, autokeratometer, automatic chart projector and patient-driven vision tester in one instrument. An "intelligent" software program guides the patient through the refraction process with pre-selected voice prompts. The patient uses a joystick to respond to the practitioner-selected sequence and completes the refraction without the aid of a skilled technician. Clinical studies have validated BV-1000 refraction results as repeatable and accurate. For more information, call 800-223-1130 or go to www.topcon.com.
  • MEDICARE AND MEDICAID SERVICES TO REIMBURSE FOR OCCULT AND MINIMALLY CLASSIC AMD LESIONS. QLT Inc. and Novartis Pharma AG recently learned that the Centers for Medicare & Medicaid Services (CMS) will reimburse patients treated with Visudyne for age-related macular degeneration (AMD) with occult and minimally classic lesions that are four disc areas or less in size and have evidence of recent disease progression. Until this decision by CMS, Medicaid has only covered patients with classic age-related macular degeneration. It will now also cover treatment for those with the occult and minimally classic form of the disease, a leading cause of blindness in people older than 50.
  • STAAR SURGICAL UNCERTAIN ON LENS LAUNCH DATE. Staar Surgical Co. is uncertain whether it can release a new implantable contact lens by April as planned, because of problems raised by federal regulators. Company officials met with the FDA last week to discuss corrective action the FDA was taking after it issued a warning letter to the company on December 29, 2003. The letter stated that Staar had not developed adequate reporting procedures for injuries related to the use of cartridges and injectors for foldable intraocular lenses. It also required Staar to assure that test results on the implantable lenses, as well as on the patented material used in the lenses, were validated by an outside laboratory. Staar says it has no indication when the FDA will respond to the corrective measures it has taken in response to the warning letter but will issue a news release when it receives a response. The company will not request a re-audit by the FDA until it is certain that it has fully addressed the concerns of regulators.

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