Volume 4, Number 33

Monday, August 16, 2004

In this issue: (click heading to view article)
		Impact of Visual Impairment on Self-reported Visual Functioning in Latinos: The Los Angeles Latino Eye Study
		Retinal Vessel Diameter Response to Flicker Stimulation in Patients with Early OAG
		Ophthalmic Drug Delivery Through Contact Lenses
		Ocular Presentation of Primary Central Nervous System Lymphoma
		Cardiovascular Therapy and Onset/Recurrence of Preretinal and Vitreous Hemorrhage in Diabetics
		Briefly

Impact of Visual Impairment on Self-reported Visual Functioning in Latinos: The Los Angeles Latino Eye Study Researchers at the Doheny Eye Institute and the Department of Ophthalmology of the Keck School of Medicine, University of Southern California, Los Angeles, formulated the Los Angeles Latino Eye Study (LALES), a population-based assessment of the prevalence of visual impairment, ocular disease and visual functioning in Latinos. The Department of Pharmaceutical Economics and Policy at the University of Southern California, Los Angeles, assessed the association between presenting binocular visual acuity (VA) and self-reported visual function as measured by the 25-item National Eye Institute Visual Function Questionnaire (NEI-VFQ-25) in individuals eligible for the LALES. A total of 6,357 Latinos (out of 7,789 eligible individuals) aged 40 and older from six census tracts in Los Angeles were included the LALES. All participants completed a standardized interview, including the NEI-VFQ-25 to measure visual functioning, and a detailed eye examination. Two definitions of visual impairment were used: presenting binocular distance visual acuity (VA) of 20/40 or worse; and presenting binocular distance VA worse than 20/40. Analysis of variance was used to determine any systematic differences in mean NEI-VFQ-25 scores by visual impairment. Regression analyses were completed to determine the association of age, gender, number of systemic comorbidities, depression and VA with self-reported visual function and to estimate a visual impairment-related difference for each subscale based on differences in VA. Of the 5,287 LALES participants with complete NEI-VFQ-25 data, 6.3 percent (including 20/40) and 4.2 percent (excluding 20/40) were visually impaired. In the visually impaired participants, the NEI-VFQ-25 subscale scores ranged from 46.2 (General Health) to 93.8 (Color Vision). In the regression model, only VA, depression and number of comorbidities were significantly associated with all subscale scores (R(2) ranged from 0.09 for Ocular Pain to 0.33 for the composite score). For nine of 11 subscales, a five-point change was equivalent to a one- or two-line difference in VA. Relationships were similar, regardless of the definition of visual impairment. Results showed that the NEI-VFQ-25 was sensitive to differences in VA. A five-point difference on the NEI-VFQ-25 seems to be a minimal criterion for a visual impairment-related difference. Self-reported visual function is essentially unchanged if the definition of visual impairment includes or excludes a VA of 20/40.

SOURCE: Globe DR, Wu J, Azen SP, Varma R (Los Angeles Latino Eye Study Group). The impact of visual impairment on self-reported visual functioning in Latinos: The Los Angeles Latino Eye Study. Ophthalmol 2004;111(6):1141-9.

Retinal Vessel Diameter Response to Flicker Stimulation in Patients with Early OAG Diffuse luminance flicker increases retinal vessel diameters in animals and humans, indicating the ability of the retina to adapt to different metabolic demands. Flicker-induced vasodilatation of retinal veins is significantly diminished in patients with glaucoma compared with healthy volunteers, indicating that regulation of retinal vascular tone is impaired in patients with early glaucoma, independently of anti-glaucoma medication, according to researchers at the University of Vienna, Austria. The study included 31 patients with early-stage glaucoma (washout for anti-glaucoma medication) and 31 age- and sex-matched healthy volunteers. Researchers measured retinal vessel diameters continuously with a Retinal Vessel Analyzer. During these measurements, three episodes of square wave flicker stimulation periods (16, 32 and 64 secs; 8 Hz) were applied through the illumination pathway of the retinal vessel analyzer. Flicker-induced vasodilatation in retinal veins was significantly diminished in glaucoma patients, compared with healthy volunteers. In healthy volunteers, retinal venous vessel diameters increased by 1.1 +/- 1.8 percent (16 seconds), 2.0 +/- 2.6 percent (32 seconds) and 2.1 +/- 2.1 percent (64 seconds) during flicker stimulation. In glaucoma patients, venous vessel diameters increased by 0.2 +/- 1.7 percent (16 seconds), 1.1 +/- 2.1 percent (32 seconds) and 0.8 +/- 2.5 percent (64 seconds). In retinal arteries, investigators observed no significant difference in flicker response between the two groups. In healthy controls, flicker stimulation increased retinal arterial vessel diameters by 1.0 +/- 2.4 percent, 1.6 +/-3.2 percent and 2.4 +/- 2.6 percent during 16, 32 and 64 seconds of flicker, respectively. In glaucoma patients, flickering light changed arterial vessel diameters by 0.3 +/-2.6 percent (16 seconds), 1.3 +/-3.1 percent (32 seconds) and 1.8 +/- 3.8 percent (64 seconds).

SOURCE: Garhofer G, Zawinka C, Resch H, et al. Response of retinal vessel diameters to flicker stimulation in patients with early open angle glaucoma. J Glaucoma 2004;13(4):340-4.

Ophthalmic Drug Delivery Through Contact Lenses Currently available ophthalmic drug delivery systems are inefficient and may lead to side effects. To increase efficiency and reduce side effects, investigators at the University of Florida"s Chemical Engineering Department proposed a disposable particle-laden soft contact lens for ophthalmic drug delivery. The essential idea behind the project was to encapsulate ophthalmic drug formulations in nanoparticles and disperse the drug-laden particles in the lens material, such as poly-2-hydroxyethyl methacrylate (p-HEMA) hydrogels. The researchers synthesized the drug-laden p-HEMA hydrogels by free-radical solution polymerization of the monomers in presence of nanoparticles. The particle-laden hydrogels were characterized by light-transmission and electron microscopy studies. Release profiles of lidocaine, a model hydrophobic drug, were measured by UV-Vis spectrophotometry. Results showed that microemulsions of hexadecane in water, stabilized with a silica shell around the particles, produced transparent hydrogels. Contact lenses made with particle-laden hydrogels released therapeutic levels of drug for a few days. The authors of the study believe that particle-laden hydrogels are promising candidates for ophthalmic drug delivery because they are transparent and can release drugs for extended periods. They propose that drug delivery rates can be controlled by varying the loading of nanoparticles in the gel.

SOURCE: Gulsen D, Chauhan A. Ophthalmic drug delivery through contact lenses. Invest Ophthalmol Vis Sci 2004;45(7):2342-7.

Ocular Presentation of Primary Central Nervous System Lymphoma Primary ocular lymphoma (POL), a lymphoma of the globe, is a restricted form of primary central nervous system lymphoma (PCNSL) that often progresses to the brain and meninges; frequently it is misdiagnosed until central nervous system (CNS) lymphoma develops. The optimal treatment has not yet been identified. Researchers at New York"s Memorial Sloan-Kettering Cancer Center Department of Neurology retrospectively reviewed the course and the treatment of POL in 31 patients. Seventeen of the 31 patients were treated for isolated POL (group A) and 14 were treated only after CNS disease was diagnosed (group B). The treatment in both groups consisted of systemic chemotherapy, chemotherapy plus radiotherapy (RT) or RT alone. In group A, nine patients (53 percent) developed CNS progression and five (29 percent) had ocular recurrence. In group B, seven (50 percent) had CNS progression and three (21 percent) ocular relapse. To control for diagnostic lead time, median survival was calculated from initial ocular symptoms and was 60 months in group A and 35 months in group B. Ocular lymphoma responds to a variety of therapies but treatment with chemotherapy and/or ocular radiotherapy (ORT) failed to prevent CNS progression. Patients whose ocular disease was identified and treated before CNS progression had a significantly improved survival rate.

SOURCE: Hormigo A, Abrey L, Heinemann MH, DeAngelis LM. Ocular presentation of primary central nervous system lymphoma: diagnosis and treatment. Br J Hematol 2004;126(2):202-8.

Cardiovascular Therapy and Onset/Recurrence of Preretinal and Vitreous Hemorrhage in Diabetics Investigators in Birmingham, England, conducted a retrospective case notes analysis of diabetic patients with vitreous hemorrhage to determine the role of cardiovascular disease and therapy in the onset and recurrence of preretinal/vitreous hemorrhage in diabetic patients. The analysis was conducted using the records of 54 patients (mean age 57.1, 37 males, 20 Type I vs. 34 Type II diabetic patients) at the Diabetic Eye Clinic at Birmingham Heartlands Hospital. The mean (SD) duration of diagnosed diabetes at first vitreous hemorrhage was significantly longer, 21.9 (7.6) years for Type I and 14.8 (9.3) years for Type II diabetic patients. Aspirin administration was not associated with a significantly later onset of vitreous hemorrhage. Four episodes were associated with ACE-inhibitor cough. There was a trend towards HMGCoA reductase inhibitor (statin) use being associated with a delayed onset of vitreous hemorrhage: 21.4 years until vitreous hemorrhage (treatment group) vs. 16.2 years (non-treatment group). During follow-up 56 recurrences occurred, making a total of 110 episodes of vitreous hemorrhage in 79 eyes of 54 patients. The mean (range) follow-up post-hemorrhage was 1,067 (77 to 3,842) days, with an average of 1.02 recurrences. Age, gender, diabetes type (I or II) or control, presence of hypertension or hypercholesterolemia and macrovascular complications were not associated with a significant effect on the one-year recurrence rate. Aspirin and other antiplatelet or anticoagulant agents and ACE- inhibitors appeared neither to increase nor decrease the one-year recurrence rate. However, statin use was significantly associated with a reduction in recurrence. Investigators concluded that the onset of preretinal/vitreous hemorrhage is not accelerated by gender, hypertension, hypercholesterolemia, evidence of macrovascular disease or HbA1c.

SOURCE: Banerjee S, Denniston AKO, Gibson JM, Dodson PM. Does cardiovascular therapy affect the onset and recurrence of preretinal and vitreous hemorrhage in diabetic eye disease? Eye 2004;18:821-5.

 

BRIEFLY ACUITY PHARMACEUTICALS FILES FIRST-EVER IND FOR THERAPEUTIC RNAi. Acuity Pharmaceuticals has filed an Investigational New Drug application (IND) with the FDA to initiate Phase I clinical trials of Cand5, its lead product candidate for treatment of wet age-related macular degeneration (AMD). Cand5 is a small interfering RNA (siRNA) that uses RNA interference (RNAi) to shut down genes that promote the overgrowth of blood vessels that leads to vision loss in wet AMD. Cand5 shuts down the production of vascular endothelial growth factor (VEGF), shown to be the central stimulus in the development of wet AMD and diabetic retinopathy. The efficacy of Cand5 in reducing the new blood vessel growth and leakage that cause AMD has been demonstrated in primates and rodents. Acuity is the first company to file an IND to take an siRNA therapeutic into clinical trials. The siRNA mechanism of action is expected to give Cand5 efficacy, safety and administration advantages compared to other compounds in development for AMD. Pending FDA review, Phase I studies are scheduled to begin in September 2004. For more information, go to www.acuitypharma.com. WAVEFRONT TECHNOLOGY MAY HELP PATIENTS RECEIVE EARLIER CATARACT TREATMENT. A recent study in the Journal of Cataract and Refractive Surgery reported that wavefront technology offers a widely accepted means for corroborating cataract patients" vision complaints, and that this may lead to earlier treatment with attendant enhanced patient safety and less loss of quality of life. The study, performed at the Departments of Ophthalmology at the University of Auckland and the Auckland Public Hospital in New Zealand, found that different types of cataracts produced identifiable and repeatable results using wavefront diagnostic equipment. This may explain the significant visual symptoms in patients with early cataracts that the most commonly used vision test does not demonstrate, and may provide insurance companies with a reliable and widely accepted means of testing for the effects of cataracts on patients" vision and for making reliable determinations of the medical need for a cataract operation. Using wavefront technology in this way might reduce the number of patients who are unable to receive early treatment because alternative testing means are inadequate or not widely accepted. GENE FOR EYE DEVELOPMENT MIGHT PLAY A ROLE IN MYOPIA. A gene basic to the development of the eye may also hold the key to myopia, according to British researchers reporting in the August 2004 issue of American Journal of Human Genetics. The authors of the study believe that their findings reinforce the much-debated idea that some children are born susceptible to becoming nearsighted and that too much reading or other close work can encourage its development. The gene, called PAX6 by the researchers, may be involved in the growth of the eye. Investigators screened 221 pairs of twins for genetic makeup and found common genetic sequences on chromosome 11 in the myopic children. They discovered that this suspect area was very close to PAX6, a fundamental gene for eye development. This suggests that PAX6 may play a role in myopia development, possibly because of genetic variation in an upstream promoter or regulator, although no definite association between PAX6 common variants and myopia was demonstrated. The research team is currently looking for the regulators of PAX6.

 

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