Volume 3, Number 26

Monday, June 30, 2003

In this issue: (click heading to view article)
		Amniotic Membrane May Provide a Support for Human RPE Cell Growth
		Predicting Proliferative Diabetic Retinopathy in Patients with Younger-Onset Type 1 Diabetes
		Identifying Glaucomatous Optic Nerve Progression by Scanning Laser Tomography
		Silicone Oil vs. Gas Tamponade for Treating Idiopathic Full-Thickness Macular Hole
		Briefly

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Amniotic Membrane May Provide a Support for Human RPE Cell Growth Amniotic membrane may be a suitable substrate for human retinal pigment epithelium (hRPE) growth, according to a study by researchers in Santiago, Spain. Human amniotic membrane (hAM) was studied for its viability as an adequate support for transplantation of an hRPE cell monolayer with preserved cell polarity to the subretinal space. Researchers aimed to culture hRPE cells over hAM. They obtained hAM from pregnant women undergoing Cesarean section, sectioned the hAM and fixed the pieces to culture dishes. They cultured hRPE cells from adult corneal donors and seeded them over hAM. They obtained phase-contrast photographs and processed selected specimens transmission electronic microscopy (TEM). Results showed attachment and growth of hRPE cells over hAM. Human RPE cells constituted tight colonies that maintained epithelial phenotype. Using TEM, researchers identified a monolayer of hRPE cells with cuboidal to spheroidal morphology. These cells showed integration with the substrate and cell-cell contacts were detected. The authors comment that further studies are required in order to determine the viability of hRPE on hAM in the subretinal space.

SOURCE: Capeáns C, Piñeiro A, Pardo M, et al. Amniotic membrane as support for human retinal pigment epithelium (RPE) cell growth. Acta Ophthalmol Scan 2003;81(3):271.

Predicting Proliferative Diabetic Retinopathy in Patients with Younger-Onset Type 1 Diabetes The relationship between specific human leukocyte antigens (HLAs) and proliferative diabetic retinopathy (PDR) may help to assess the genetic basis of PDA in younger Type 1 diabetic patients, according to a recent Tokyo study. In a retrospective, nonrandomized comparative trial, researchers studied patients who were diagnosed with Type 1 diabetes younger than 30 years of age (range 13–28) and who had a disease duration of more than 10 years. The patients were divided into two groups: 30 patients who had undergone vitreous surgery younger than 40 years old (the PDR group) and 50 patients without retinopathy (the non–DR group). The duration of diabetes and the level of glycemic control were matched between the two groups. A control group consisted of 50 healthy patients. Researchers completed HLA-A, -B, -C, -DR and -DQ typing of blood samples using the standard microcytotoxicity method. The frequency of HLA-B62, Cw4, and DQ4 was significantly higher in the PDR group than in the non–DR group. The Cw4-DR4-DQ4 haplotype frequency was significantly higher in the PDR group than in the control group and the non–DR group. Researchers concluded that HLA-B62, Cw4, and DQ4 may be useful for predicting the prognosis of retinopathy in patients with younger-onset Type 1 diabetes.

SOURCES: Mimura T, Funatsu H, Uchigata Y, et al. Relationship between human leukocyte antigen status and proliferative diabetic retinopathy in patients with younger-onset Type 1 diabetes mellitus. Amer J Ophthalmol 2003;135(6):844-8.

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Identifying Glaucomatous Optic Nerve Progression by Scanning Laser Tomography A new analytical approach for identifying glaucomatous optic nerve change by scanning laser tomography helps distinguish eyes with progressive glaucoma from unchanging normal control eyes, say researchers at London’s Moorfields Eye Hospital. The approach analyzed 30 degrees sectors of rim area using a novel and reproducible experimental reference plane. It also estimated and accounted for measurement variability in each sector and required that any change exceeding variability in a single (positive) test should be confirmed as repeatable by a criterion requiring two of three consecutive tests to be positive. The sensitivity and false-positive rate of a single positive test and the two-of-three criterion were assessed in image series of one eye each of 20 ocular hypertension patients who converted to glaucoma (referred to as converters) who had unambiguous disease progression, and in one eye each of 20 normal control subjects. Eighteen of 20 (90 percent sensitivity) converters and 7 of 20 (35 percent false-positive responses) control subjects had single positive test results, but with confirmation by the two-of-three criterion, the false-positive rate improved to 5 percent (1 out of 20), whereas sensitivity was relatively preserved at 85 percent (17 out of 20). Estimates of rim area variability in each sector of each nerve allowed change consistent with disease progression to be distinguished from measurement variability. Confirming that change is repeatable by the criterion used in the study resulted in considerably fewer false-positive responses than did testing without confirmation, but with sensitivity not significantly compromised in the former.

SOURCE: Tan JC, Hitchings RA. Approach for identifying glaucomatous optic nerve progression by scanning laser tomography. Invest Ophthalmol Vis Sci 2003;44(6):2621-6.

Silicone Oil vs. Gas Tamponade for Treating Idiopathic Full-Thickness Macular Hole Perfluoropropane (C3F8) gas is a more effective tamponade than silicone oil for achieving initial closure of macular holes, according to a study by North Carolina’s Duke University Medical Center. Eyes receiving an oil tamponade required significantly more reoperations to achieve a similar rate of hole closure compared with eyes undergoing a gas tamponade. Final visual acuity was better for gas-operated eyes than for silicone-operated eyes. In a retrospective, comparative interventional study, 54 eyes of 51 patients underwent pars plana vitrectomy for macular holes. Thirty-one eyes were treated with silicone oil tamponade, and 23 eyes were treated with C3F8 tamponade. Main outcome measures were preoperative and postoperative visual acuity, initial hole closure, number of persistent or recurrent holes, number of reoperations and final hole closure. The silicone oil and gas tamponade groups were demographically similar. The rate of hole closure after one operation with oil tamponade was significantly lower than that with gas tamponade (65 percent vs. 91 percent). The percentage of patients undergoing a second operation was significantly higher in the oil group (35 percent vs. 4 percent); however, with reoperations, the final rate of hole closure was similar between the oil and gas groups (90 percent vs. 96 percent). The final median visual acuity for the gas group was significantly better than for the oil group (20/50 vs. 20/70).

SOURCE: Lai JC, Stinnett SS, McCuen BW. Comparison of silicone oil versus gas tamponade in the treatment of idiopathic full-thickness macular hole. Ophthalmol 2003;110(6):1170-4.

BRIEFLY TRIAL SET TO LAUNCH FOR TRABECULECTOMY ANTI-SCARRING AGENT. Cambridge Antibody Technology (CAT), based near Cambridge, Great Britain, recently announced the completion of a Phase II/III European clinical trial of Trabio, a human monoclonal antibody under development as an anti-scarring agent to improve the outcome of glaucoma filtration surgery. (Six other CAT-derived human therapeutic antibodies are at various stages of clinical trials; Humira, the leading CAT-derived antibody, isolated and optimized in collaboration with Abbott, has been approved by the FDA for marketing in the United States as a treatment for rheumatoid arthritis.) The current trial includes 344 patients undergoing first-time trabeculectomy, enrolled at major eye hospitals in six European countries. Data from the trial is expected to be available at the end of 2004. THREE CELL TYPES RESPONSIBLE FOR LIGHT DETECTION IN THE EYE. A team of researchers from Johns Hopkins has put to rest a long-standing controversy over how many cell types are responsible for detecting light in the eye. The answer: three. In the June 15 advance online publication of Nature, researchers announced that rods, cones and special retinal cells that produce a protein called melanopsin account for the entirety of a mouse’s reaction to light levels. They discount the idea that cells that produce proteins called cryptochromes are somehow connected to light detection. Along with producing visual images, detecting and reacting to light is among one of the eye’s most important functions, helping to regulate the body’s internal clock, the pupil’s ability to react to light, and the motivation toward activity at appropriate times of the day. The Johns Hopkins team removed the genes for three key proteins that help pass light information from rods, cones and melanopsin-producing cells. Offspring from these cross-bred knockout mice were missing all three proteins, had a "half-dose" of the three proteins or had various combinations of protein levels. None of the so-called triple-knockout mice could adjust their pupils in response to light; nor did they adjust activity levels when exposed to light, although the mice with a half-dose of each of the three proteins reacted normally. Additional tests showed that mice without rods and cones were able to reset their internal clocks when exposed to the same color of light favored by melanopsin-producing cells--but not by cryptochromes. SOURCE: Hattar S, Lucas RJ, Mrosovsky N, et al. Melanopsin and rod-cone photoreceptive systems account for all major accessory visual functions in mice. Nature AOP, published online June 15, 2003;doi:10.1038/nature01761.

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