Richard Hackel

Anti–Retinal Pigment Epithelium Antibodies in Acute Exudative Polymorphous Vitelliform Maculopathy: A New Hypothesis About Disease Pathogenesis

OBJECTIVE To investigate the etiology of acute exudative polymorphous vitelliform maculopathy (AEPVM) in a patient with metastatic melanoma, undiagnosed at initial examination, by testing for autoimmune mechanisms. METHODS Serum samples were obtained from a 50-year-old man with AEPVM and metastatic unknown primary melanoma during the acute stage and 3 years later when subretinal fluid had resolved and melanoma was in remission (AEPVM convalescent stage). Western immunoblots using both serum samples against human donor retinal extract and cultured primary human retinal pigment epithelium (RPE) cell extract were performed to identify antiretinal and anti-RPE antibodies. Serum samples from 5 unaffected participants were tested as controls. Protein identification was performed using 2-dimensional gel electrophoresis and mass spectrometry and was then confirmed by blotting against purified protein. RESULTS Western immunoblots of the patients serum against human donor retinal extract and RPE cell extract demonstrated several antiretinal antibodies, as well as anti-RPE antibodies against a 26-kDa protein that was identified as peroxiredoxin 3 (PRDX3). Serum reactivity against PRDX3 was greatly decreased in the convalescent-stage serum sample compared with the acute-stage serum sample, while results of retinal extract Western immunoblots remained essentially unchanged. Five separate serum samples from participants without AEPVM had no autoantibodies against PRDX3. CONCLUSIONS Paraneoplastic autoimmune reaction against RPE, with PRDX3 as the putative antigen, may be a cause of AEPVM. This is the first report to date linking a human RPE disease with anti-RPE antibodies against a heretofore undetermined putative protein. Testing for RPE autoantibodies may be useful in exploring the pathogenesis of other presumed RPE-related diseases.

Rapid, Noninvasive Detection of Diabetes-Induced Retinal Metabolic Stress

OBJECTIVE To test whether subjects with diabetes mellitus (DM) have enhanced retinal flavoprotein autofluorescence compared with age-matched control subjects using a rapid, noninvasive clinical imaging method. METHODS Twenty-one subjects with DM and 21 healthy age-matched control volunteers were subjected to retinal imaging using 1-ms flashes of 467-nm light. Flavoprotein autofluorescence for each flash at 535 nm was recorded using an electron-multiplying charged-coupled device camera with a 512x512-pixel chip. The average intensity and the average curve width of retinal flavoprotein autofluorescence were determined by analyzing histograms of pixel intensities plotted for each eye. RESULTS When stratified by age, the mean average intensity and average curve width levels in subjects with DM were significantly greater than those in controls across all 3 consecutive decades of life studied (P < or = .004 and P < or = .006, respectively). An overall comparison of the mean average intensity and average curve width levels in all subjects with DM vs all controls, with adjustment for age, was consistent with the results found in each age category (P =.001 and P < .001, respectively). Subjects having DM with retinopathy in at least 1 eye had significantly greater average intensity and average curve width than subjects having DM without retinopathy in either eye (P =.002 and P =.005, respectively). CONCLUSIONS Flavoprotein autofluorescence measurements may be clinically useful to rapidly and noninvasively identify diabetic metabolic tissue stress and disease severity. Development of flavoprotein autofluorescence technology is likely to result in a tool that will improve DM screening and disease management.

Flavoprotein autofluorescence detection of early ocular dysfunction.

Metabolic stress occurs at disease onset and causes altered flavoprotein redox activity that increases flavoprotein autofluorescence (FA). Using a new method to measure ocular FA, we studied women with subtle visual dysfunction due to pseudotumor cerebri. Each FA value was greater in the more affected eye of each woman with pseudotumor cerebri, permitting identification of that eye in each case. Flavoprotein autofluorescence values averaged 60% greater in more affected eyes of women with pseudotumor cerebri, but not between eyes of healthy women (control subjects). These results demonstrate the clinical utility of FA and may permit early detection and monitoring of retinal and optic nerve diseases.

Detection of retinal metabolic stress resulting from central serous retinopathy.

Purpose: To test whether eyes with central serous retinopathy have elevated retinal flavoprotein fluorescence (FPF) using a novel clinical imaging method. Methods: Three male patients with unilateral central serous retinopathy were examined for FPF at 535 nm induced by 1-msec flashes of 467 nm light. FPF was captured with an electron multiplying charged-coupled device camera with a 512 × 512 pixel chip. Average intensity of retinal FPF for each affected eye was compared with the contralateral, unaffected eye and with six age-matched control eyes by analyzing histograms of pixel intensities plotted for each eye. Results: For each patient, the central serous retinopathy-affected eye had a significantly greater retinal FPF when compared with the retinal FPF of the unaffected eye. Eyes affected with central serous retinopathy had retinal FPF values that averaged 98% greater than the retinal FPF of age-matched control eyes. Conclusion: Flavoprotein fluorescence analysis may be useful for rapidly and noninvasively identifying metabolic tissue stress of central serous retinopathy.

Subretinal Candida albicans abscesses responsive to oral voriconazole.

PURPOSE To report findings in a patient with bilateral Candida albicans subretinal abscesses responsive to oral voriconazole. METHODS Retrospective, case report. RESULTS A 62-year-old woman presented with bilateral C albicans subretinal abscesses secondary to chronic immunosuppression. The abscesses responded to oral voriconazole and resolved completely within 4 months of initial presentation. CONCLUSIONS This case illustrates that oral voriconazole may be effective in the treatment of large subretinal abscesses in an immunocompromised patient. Additionally, this report suggests that a subretinal aspirate may have greater diagnostic sensitivity than a vitreous specimen in eyes with infectious subretinal abscesses.