Volume 5, Number 6
Monday, February 14, 2005



In this issue: (click heading to view article)
Diabetic Retinopathy and Preclinical Diabetic Glomerulopathy Lesions in Type I Patients
Altered Metabolism of Cholesterol in Pterygium and Pinguecula
Anti-inflammatory Therapy in Graves" Ophthalmopathy and Association with Thyroidal Autoantibodies
Glaucoma, Motor Vehicle Collision Involvement and Driving Avoidance in Older People
Briefly











Diabetic Retinopathy and Preclinical Diabetic Glomerulopathy Lesions in Type I Patients

Few epidemiological data exist regarding the correlation of anatomic measures of diabetic retinopathy and nephropathy, especially early in the disease processes. Investigators at the University of Wisconsin at Madison aimed to examine the association of severity of diabetic retinopathy with histological measures of diabetic nephropathy in normoalbuminuric patients with Type I diabetes.

The study included 285 participants in the Renin-Angiotensin System Study (RASS), a multicenter diabetic nephropathy primary prevention trial, who were aged 16 or older and had two to 20 years of Type I diabetes with normal baseline renal function measures. Albumin excretion rate (AER), blood pressure, serum creatinine and glomerular filtration rate (GFR) were measured using standardized protocols. Clinicians determined diabetic retinopathy by masked grading of 30 degrees color stereoscopic fundus photographs of seven standard fields using the Early Treatment Diabetic Retinopathy Study severity scale. They assessed baseline renal structural parameters--for example, fraction of the glomerulus occupied by the mesangium or mesangial fractional volume (Vv[Mes/glom]) and glomerular basement membrane width--using masked electron microscopic morphometric analyses of research percutaneous renal biopsies.

No retinopathy was present in 36 percent, mild nonproliferative diabetic retinopathy in 53 percent, moderate to severe nonproliferative diabetic retinopathy in 9 percent and proliferative diabetic retinopathy in 2 percent of the study cohort. Retinopathy was not related to AER, blood pressure, serum creatinine or GFR. All renal anatomical endpoints were associated with increasing severity of diabetic retinopathy, while controlling for other risk factors. The results suggest a significant association between diabetic retinopathy and preclinical morphologic changes of diabetic nephropathy in Type I diabetic patients.

SOURCE: Klein R, Zinman B, Gardiner R, et al. The relationship of diabetic retinopathy to preclinical diabetic glomerulopathy lesions in type 1 diabetic patients: the Renin-Angiotensin system study. Diabetes 2005;54(2):527-33. 		Table of Contents











Altered Metabolism of Cholesterol in Pterygium and Pinguecula

There is increasing evidence that pterygium and pinguecula are tumorlike tissues and that cell growth and DNA replication are closely linked to cholesterol metabolism. In this study by Italy’s University of Calgiri Eye Clinic, the expression of two main genes correlated to cholesterol metabolism--namely, the low-density lipoprotein receptor (LDL-R) gene and the hydroxy-methylglutaryl-coenzyme A-reductase (HMG-CoA-R) gene--were investigated in primary pterygium, pinguecula and normal conjunctiva.

Pterygium, pinguecula, and normal conjunctiva samples were obtained from 30 eyes (15 men and 15 women) at the time of surgery. Investigators subjected total RNA extracted from the specimens to semiquantitative reverse transcription-polymerase chain reaction (RT-PCR). Equal amounts of total RNA were reverse transcribed into cDNA. The cDNA was subsequently amplified by the PCR in the presence of specific primers for low-density lipoprotein receptor (LDL-R) and for hydroxy-methylglutaryl coenzyme A reductase (HMG-CoA-R).

RT-PCR analysis revealed that the mRNA levels of LDL-R and HMG-CoA-R were increased in pterygia, compared with levels in both pingueculae and normal conjunctivae. Differences were statistically significant, including pingueculae versus normal conjunctivae. The authors of the study believe that this indicates that pterygium and pinguecula have an altered metabolism of cholesterol, as is characteristic of tumorlike tissues, and that the high expression of LDL receptors renders them amenable to be treated by photodynamic therapy with intravenously injected verteporfin.

SOURCE: Peiretti E, Dessi S, Putzolu M, Fossarello M. Hyperexpression of low-density lipoprotein receptors and hydroxy-methylglutaryl-coenzyme A-reductase in human pinguecula and primary pterygium. Invest Ophthalmol Vis Sci 2004;45(11):3982-5.		 Table of Contents











Anti-inflammatory Therapy in Graves" Ophthalmopathy and Association with Thyroidal Autoantibodies

Graves" ophthalmopathy (GO) is clinically associated with autoimmune thyroid disease, and autoantibodies to thyroidal antigens, especially to the TSH-receptor (TRAb), might be involved in the disease process. While there is mounting evidence that TRAb are associated with GO at the onset of the disease, no studies thus far have examined the association between thyroidal autoantibodies and the clinical outcome of GO therapy. The aim of this retrospective study by Germany’s University of Essen was to evaluate whether TSH binding inhibitory immunoglobulins (TBII) and thyroid-stimulating antibodies (TSAb) are still associated with the clinical activity and severity of GO after the completion of anti-inflammatory therapy. Investigators also wanted to elucidate whether thyroid peroxidase (TPO) or thyroglobulin (TG) autoantibodies (TPOAb and TGAb) are in any way related to GO.

Researchers assessed clinical activity score (CAS) and the severity of GO (modified NOSPECS score) in 108 patients with GO after steroid therapy and, if indicated, orbital irradiation. Patients were grouped according to their clinical presentation and autoantibody levels (TBII, TSAb, TPOAb and TGAb) were measured. After therapy for hyperthyroidism, all patients were clinically euthyroid but showed clear heterogeneity for GO four to 12 months after the end of anti-inflammatory therapy. Fifty-two patients had inactive GO, 41 had moderately active GO and 15 continued to have very active (non-responsive) GO. As for severity, 27 patients had mild GO, 64 had moderately severe GO and 17 had severe GO.

TBII titres were still positive in 14 (93 percent) of 15 patients in the non-responsive group (CAS > 6) compared to 22 (42 percent) of 52 patients with post-therapeutic inactive GO (CAS </= 2). Similar results occurred between TBII levels and the NOSPECS score. The simultaneous presence of TBII and TSAb was associated with significantly higher activity and severity than the presence of TBII without measurable TSAb in comparison to absence of both antibodies. Only TBII and TSAb, but not TPOAb or TGAb medians, increased statistically significantly with CAS or NOSPECS scores. Both scores were positively associated with TBII and, to a lesser degree, with TSAb. This association was independent of the treatment of hyperthyroidism, although highest levels of TBII were seen after radioiodine treatment. The NOSPECS score was negatively associated with TGAb but not with TPOAb; both showed no association with the CAS score.

Investigators concluded that the persistence of TBII and TSAb levels in patients with therapy-resistant disease compared to patients with inactive disease supports the role of TRAb in the pathogenesis of GO. They also believe that the fact that TBII and TSAb levels and prevalence still correlate with the severity and activity of GO even after anti-inflammatory therapy suggests not only a trigger but also a possible role in the maintenance of the autoimmune process in the orbits.

SOURCE: Eckstein AK, Plicht M, Lax H, et al. Clinical results of anti-inflammatory therapy in Graves" ophthalmopathy and association with thyroidal autoantibodies. Clin Endocrinol (Oxf) 2004;61(5):612-8. 		Table of Contents






Glaucoma, Motor Vehicle Collision Involvement and Driving Avoidance in Older People

Older people with glaucoma drive at least as safely as, if not more safely than, older people who do not have glaucoma, according to a recent study by the University of Alabama at Birmingham and the College of Optometry, Nova Southeastern University, Fort Lauderdale, FL.

Investigators aimed to evaluate the association between the diagnosis of glaucoma and motor vehicle collision (MVC) involvement and driving avoidance in drivers 50 years or older. In three university-affiliated eyecare practices, they identified two groups of patients, one consisting of people who had glaucoma and one of people who did not have the disease. They obtained demographic, clinical and driving characteristics by chart abstractions and a patient survey. Information regarding MVC involvement was obtained from police records.

Results showed that patients with glaucoma were less likely to be involved in collisions than patients without glaucoma. No difference was evident between the at-fault crash rates of the patients with glaucoma and those without. Patients with glaucoma had significantly higher levels of avoidance for driving at night, driving in fog, driving in the rain, driving during rush hour, driving on highways and high-density driving. These associations were adjusted for demographic and medical characteristics as well as visual acuity.

SOURCE: McGwin G Jr, Mays A, Joiner W, et al. Is glaucoma associated with motor vehicle collision involvement and driving avoidance? Invest Ophthalmol Vis Sci 2004;45(11):3934-9. 		Table of Contents





BRIEFLY
  • DRY EYE TREATMENT FAILS IN LATE-STAGE STUDY. Inspire Pharmaceuticals, Inc., says that compared with placebo, its dry eye treatment, diquafosol tetrasodium, did not significantly improve corneal clearing, the trial’s primary endpoint, in its six-week Phase III study. The compound also failed to reach secondary endpoints based on the Ocular Surface Disease Index, but its effect on corneal staining, conjunctival staining and conjunctival clearing was consistent with results of previous late-stage studies, according to Inspire. Patients using diquafosol tetrasodium reported burning or stinging more often than those using the placebo, but Inspire added that the incident rate was less than five percent. Based on these results, the company held a preliminary discussion with the FDA regarding the next step for the drug. Inspire intends to file a New Drug Application amendment for diquafosol tetrasodium by the end of this year’s second quarter.
  • AMA ASSIGNS CPT CODE FOR KERATOCONUS TO INTACS PROCEDURE. The American Medical Association (AMA) has released a new Category III CPT code to cover the Intacs procedure for keratoconus. The designated code is 0099T. Category III codes are temporary codes to designate emerging technology; each code has five years to become mainstream, at which time it may be promoted to a permanent Category I code. Addition Technology, the maker of Intacs, is providing billing assistance at 1-888-846-8227. A billing monograph is also available at www.corcoranccg.com/default.asp?Location=\addition. For more information on the new CPT code, go to www.ama-assn.org/ama/pub/category/3885.html#0075T.
  • NEW HANDHELD PACHYMETER INTRODUCED. Accutome, Inc., has introduced a new handheld pachymeter, the PachPen, which uses state-of-the-art waveform analysis and a probe that samples at a 65MHz rate to obtain precise readings. The PachPen stores and averages nine measurements and calculates IOP corrections. The pen fits comfortably into the hand and weighs just three ounces. It runs on lithium batteries. For more information, call 800-979-2020 or e-mail [email protected].
  • MEDICARE/MEDICAID REIMBURSEMENT TERMS FOR MACUGEN ANNOUNCED. Effective January 1, 2005, the Centers for Medicare & Medicaid Services (CMS) posts that the Medicare part B allowable for Eyetech Pharmaceuticals’ Macugen (pegaptanib sodium injection) is 106 percent of Average Sales Price (ASP), or $1,054.70 per injection. Macugen was approved by the FDA on December 17, 2004, for treatment of neovascular (wet) age-related macular degeneration. Eyetech and Pfizer launched Macugen on January 20, 2005. For more information, go to www.cms.hhs.gov/providers/drugs/asp.asp.

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