Volume 3, Number 49
Monday, December 8, 2003



In this issue: (click heading to view article)
Drusen-associated Retinal Degeneration
Rates of Annual Eye Exams for Patients with Diabetes and Chronic Eye Diseases
Aberrant Corneal Nerve Regeneration After PRK
Light-activated Adhesive Technique for Sutureless Ophthalmic Surgery
Briefly











Drusen-associated Retinal Degeneration

Drusen--variably sized extracellular deposits that form between the retinal pigmented epithelium (RPE) and Bruch’s membrane--are commonly found in aged eyes. However, numerous and/or confluent drusen are a significant risk factor for age-related macular degeneration (AMD). Researchers at the University of California"s Center for the Study of Macular Degeneration and Department of Molecular, Cellular and Developmental Biology aimed to investigate the impact of drusen on overlying cells of the retina, and found that the retinal cells of both types of drusen exhibit structural and molecular abnormalities indicative of photoreceptor degeneration and Müller glial activation. These abnormalities resemble the degenerative effects common to many forms of retinal degeneration, but are confined to areas directly overlying drusen. The results suggest that photoreceptor cell function is compromised as a consequence of drusen formation.

In the study, researchers dissected tissue containing retina and RPE/choroid from human donor eyes, embedded it in agarose, and sectioned it at 100 µm using a vibratome. They immunostained sections with a panel of antibodies that labeled glial cells as well as first-, second- and third-order retinal neurons, and they processed for confocal microscopy.

Retinal cells overlying both soft and hard drusen exhibited numerous structural and molecular abnormalities. Rod opsin immunolabeling, normally detectable only in the outer segments of rod photoreceptors, was also observed in the inner segment, cell body, axon and axon terminal of photoreceptors that overlie drusen. Labeling with this antibody also revealed the deflection and shortening of rod inner and outer segments. Cone photoreceptors displayed similar structural abnormalities, as well as a decrease in cone opsin immunoreactivity. Results also showed drusen-associated abnormalities in the synaptic terminals of photoreceptor cells. In addition, they observed an increase in intermediate filament protein immunoreactivity (vimentin and glial fibrillary acidic protein) within Müller glial cells in areas of retina overlying drusen. Both soft and hard drusen were associated with a similar spectrum of effects in macular and extramacular regions alike. Second- and third-order neurons, including bipolar, horizontal, amacrine and ganglion cells, all appeared unaffected. The structural and molecular abnormalities observed in photoreceptors and Müller glial cells were confined to retinal regions directly overlying and immediately adjacent to drusen; more distant retinal regions appeared unperturbed. Remarkably, significant abnormalities were observed over small subclinical drusen.

SOURCE: Johnson PT, Lewis GP, Talaga KC, et al. Drusen-associated degeneration in the retina. Invest Ophthalmol Vis Sci 2003;44(10):4481-8.
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Rates of Annual Eye Exams for Patients with Diabetes and Chronic Eye Diseases

Annual eye examinations for persons diagnosed with diabetes, glaucoma, and age-related macular degeneration (AMD) are important for detecting potentially treatable vision loss among those already diagnosed with these conditions. According to a study involving a longitudinal analysis of Medicare claims data by Duke University, NC, actual rates of eye examinations for persons diagnosed with these conditions currently fall far short of recommended rates.

Researchers gathered a random sample of Medicare beneficiaries aged 65 or older and followed between 1991 and 1999, unless mortality or enrollment in a health maintenance organization for greater than six months in a given 12-month period intervened. They analyzed all claims data (both physician and facility) during this time for the presence of International Classification of Diseases 9 codes consistent with one of the three study conditions (diabetes, glaucoma, AMD) and the performance of eye examinations. Claims were submitted by optometrists, ophthalmologists or other providers of eye care. Rates were calculated on the basis of a 15-month time window for annual examinations rather than for 12 months, to allow for less than full compliance with the guidelines for various reasons (e.g., bad weather).

Among those with diabetes in this population, 50 to 60 percent had annual eye examinations in a 15-month period. Of those followed for at least 75 months after diagnosis, about 75 percent had one or more 15-month gaps between visits. For subjects diagnosed with glaucoma, most visit rates were in the 70 to 90 percent range per 15-month period. The percentage of subjects with at least one 15-month period with no visits was considerably lower than for diabetes. The patterns for those with AMD were in between those for diabetes and glaucoma. Over a nine-year period, only slightly more than 50 percent of those studied who had a least one of the three conditions complied with practice guidelines. The authors suggest that approaches to enhancing longitudinal follow-up of those already in the eye care system are necessary.

SOURCES: Lee PP, Feldman ZW, Ostermann J, et al. Longitudinal rates of annual eye examinations of persons with diabetes and chronic eye diseases. Ophthalmol 2003;110(10):1952-9.
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Aberrant Corneal Nerve Regeneration After PRK

A recent case study from the Mayo Clinic"s Department of Ophthalmology (Rochester, MN) described a patient who underwent bilateral photorefractive keratectomy (PRK) to correct a refractive error of -5.50D in each eye. Thirteen months after the original PRK, the left eye underwent an uncomplicated PRK reoperation to correct a -1.00D regression. Both central corneas were examined by confocal microscopy preoperatively in both eyes, at one and two years after the original PRK in the right eye, and before and one and two years after the PRK reoperation in the left eye.

Aberrant anterior stromal nerves with a coiled course and irregular branching pattern were identified 22 µm deep to the most anterior keratocyte layer at one year after the PRK reoperation in the left eye and remained unchanged two years after reoperation. No abnormal stromal nerves were identified in the left eye before the reoperation or at any time in the right eye. The authors of the case study concluded that aberrant regeneration of corneal stromal nerves may occur after myopic PRK reoperation.

SOURCE: Erie JC, Patel SV, Bourne WM. Aberrant corneal nerve regeneration after PRK. Cornea 2003;22(7):684-6.
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Light-activated Adhesive Technique for Sutureless Ophthalmic Surgery

Suture use in ophthalmic surgery is technically demanding and time consuming, and it may be associated with serious complications such as inadvertent ocular penetration, which can result in retinal detachment and endophthalmitis. Bioadhesive surgery could eliminate many complications and limitations associated with the use of sutures. Researchers at the University of Illinois College of Medicine have devised a scaffold-enhanced, light-activated bioadhesive technique for various ophthalmic procedures.

The bioadhesive was composed of a poly (L-lactic-co-glycolic acid) (PLGA) porous scaffold doped with a protein solder mix composed of serum albumin and indocyanine green, which was activated with a diode laser. Extraocular rectus muscle-to-extraocular rectus muscle, sclera-to-sclera, and extraocular rectus muscle-to-sclera adhesions were created in freshly harvested tissue followed by tensile-strength testing of these surgical adhesions.

Optimum tensile strength for muscle-to-muscle repair was achieved with 50 percent wt/vol bovine serum albumin and 0.5 mg/mL of indocyanine green saturated into a PLGA porous scaffold and activated with an 808-nm diode laser. The tensile strength was 81 percent of the native muscle"s tensile strength (mean +/- SD, 433 +/- 70 g vs. 494 +/- 73 g). Sclera-to-sclera adhesions achieved a mean +/- SD tensile strength of 295 +/- 38 g, whereas the tensile strength for extraocular rectus muscle-to-sclera adhesions was 309 +/- 37 g. The authors of the study conclude that the newly devised technique appears feasible and may result in reduced surgical complications and cost.

SOURCE: Bloom JN, Duffy MT, Davis JB, McNally-Heintzelman KM. A light-activated surgical adhesive technique for sutureless ophthalmic surgery. Arch Ophthalmol 2003;121(11):1591-5.
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BRIEFLY
  • ALLERGAN LOSES FINAL APPEAL ON BRIMONIDINE PATENT SUIT. Allergan, Inc., lost a final appeal in its attempt to block Alcon Inc. and Bausch & Lomb from producing a generic version of Alphagan (brimonidine) glaucoma treatment medication. Allergan"s exclusivity over the drug as a glaucoma treatment has expired, but the company sought to block other manufacturers from making generic alternatives because it alleged that Alcon and B&L were marketing the drug for use as a neuroprotective agent, for which it says it holds other patents. Lower courts, a U.S. District Court and the U.S. Circuit Court of Appeals for the Federal Circuit all rejected the argument, saying that the law did not allow Allergan to block a generic drug approval because of its potential for off-market uses. Attorneys for Allergan hope that the Supreme Court will take up the matter, but Alcon and B&L spokespersons believe that a Supreme Court review is unwarranted because the FDA is still in the process of clarifying its regulation on the issue.
  • AMO FILES PATENT COMPLAINT VS. ALCON. Advanced Medical Optics (AMO) has filed a complaint in U.S. District Court for the District of Delaware against Alcon, Inc. and Alcon Laboratories, Inc. for infringement of two of its patents for proprietary cataract-removal technology. AMO alleges that Alcon"s phacoemulsification systems marketed under the names "Infiniti" and "Series 20000 Legacy" infringe its patents, which cover advanced fluidics technologies that facilitate removal of cataracts during eye surgery and are incorporated in AMO"s Sovereign and Sovereign Compact phacoemulsification systems.
  • REFOCUS GROUP FILES FOR PHASE II CLINICAL TRIALS FOR PRESBYOPIA SURGERY. Refocus Group, Inc., announced that it has filed an investigational device exemption with the FDA to obtain approval for initiating Phase II clinical trials of the company"s Scleral Implants and Scleral Spacing Procedure for the surgical treatment of presbyopia. Subject to FDA approval, Phase II clinical trials would involve up to five investigators and sites and would involve the company"s redesigned procedure, which incorporates a mechanical incisional handpiece, disposable blade and control box and updated ultrasound mapping. Refocus Group filed the investigational device exemption in conjunction with CIBA Vision.

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