Seroreactivity against aqueous-soluble and detergent-soluble retinal proteins in posterior uveitis.

OBJECTIVE: To characterize the seroreactivity against retinal proteins in patients with posterior uveitis, retinal disease of noninflammatory origin, and healthy controls. METHODS: Patients with posterior uveitis (n = 47), molecularly confirmed photoreceptor degenerations (n = 11), and healthy controls (n = 33) received dilated fundus examinations at the University of Iowa. Aqueous-soluble and detergent-soluble fractions of human retina were separated by gel electrophoresis and transferred to polyvinylidene fluoride membranes. Membranes were probed with patient serum samples to detect IgG, IgA, and IgM human antibodies that react with retinal antigens. The number of bands detected by Western blot was counted, and their molecular weights were determined. RESULTS: Antibodies recognizing retinal proteins were found in healthy controls, in patients with posterior uveitis, and in patients with molecularly confirmed heritable retinal degenerations. In healthy controls, 42% of individuals had circulating autoantibodies that recognized retinal proteins. Healthy controls had a low odds ratio of serum reactivity to soluble antigens (0.7; 95% confidence interval [CI], 0.4-1.2). Patients with inflammatory retinal diseases and inherited retinal diseases had 4.89 (95% CI, 2.25-10.64; P < .001) and 2.71 (95% CI, 1.19-6.16; P = .02) times more activity against soluble retinal antigens compared with controls. CONCLUSIONS: Healthy control patients exhibited a significantly higher level of background autoantibody activity against retinal proteins than previously reported. Antibody activity in healthy controls was primarily directed against membrane-bound retinal proteins, whereas in patients with pathologic retinal conditions, antibodies targeting nonmembrane-bound retinal proteins predominate.

HTRA1 variant confers similar risks to geographic atrophy and neovascular age-related macular degeneration.

Age-related macular degeneration (AMD) is the most common cause of irreversible visual impairment in the developed world. The two forms of advanced AMD, geographic atrophy (GA) and choroidal neovascularization (wet AMD), represent two types of degenerative processes in the macula that lead to loss of central vision. Soft confluent drusen, characterized by deposits in macula without visual loss are considered a precursor of advanced AMD. A single nucleotide polymorphism, rs11200638, in the promoter of HTRA1 has been shown to increases the risk for wet AMD. However, its impact on soft confluent drusen and GA or the relationship between them is unclear. To better understand the role the HTRA1 polymorphism plays in AMD subtypes, we genotyped an expanded Utah population with 658 patients having advanced AMD or soft confluent drusen and 294 normal controls and found that the rs11200638 was significantly associated with GA. This association remains significant conditional on LOC387715 rs10490924. In addition, rs11200638 was significantly associated with soft confluent drusen, which are strongly immunolabeled with HTRA1 antibody in an AMD eye with GA similar to wet AMD. Two-locus analyses were performed for CFH Y402H variant at 1q31 and the HTRA1 polymorphism. Together CFH and HTRA1 risk variants increase the odds of having AMD by more than 40 times. These findings expand the role of HTRA1 in AMD. Understanding the underlying molecular mechanism will provide an important insight in pathogenesis of AMD.

Perceptions of recent ophthalmology residency graduates regarding preparation for practice.

OBJECTIVE: To evaluate young ophthalmologists' perceptions of how well residency training prepared them for various aspects of their clinical practice. DESIGN: Self-administered survey. PARTICIPANTS: Two hundred sixty-nine United States ophthalmologists who have been in practice for < or =5 years. METHODS: A 4-page questionnaire was mailed to a randomly selected sample of 900 U.S. members and fellows of the American Academy of Ophthalmology who had been in practice for < or =5 years. MAIN OUTCOME MEASURES: Comparison of perceived preparedness in clinical and nonclinical areas of ophthalmology practice. RESULTS: Two hundred sixty-nine surveys were completed and returned (margin of error, +/-5%). Analysis of tabulated results indicated that 86% said they were extremely or very well prepared to practice comprehensive ophthalmology after residency training. Even so, about half of those respondents also desired some additional clinical training, and two thirds felt the need for some additional training in surgical areas (refractive, oculoplastics/orbital, glaucoma, retina, and pediatric ophthalmic surgery). At least 60% reported being not very or not at all well prepared in 6 of the nonclinical areas explored (business operations and finance, personal financial management, practice management skills, coding and reimbursement, political advocacy, and exposure to practice setting models). With the exception of personal financial management, most ophthalmologists thought training in all of these nonclinical areas was the responsibility of the residency training program. CONCLUSION: The transition from residency training to successful, efficient, ethical, high-quality ophthalmic practice demands a number of skills in addition to diagnostic acumen and surgical ability. In general, the U.S. residency program graduates surveyed are comfortable with their clinical training, but less so with their training in nonclinical areas. Opportunities to help ophthalmologists prepare better for the transition to clinical practice after training appear to exist and might be addressed by training programs, professional organizations, informal physician networks, and other stakeholders.