Imbalance of the nerve growth factor and its precursor as a potential biomarker for diabetic retinopathy.

Our previous studies have demonstrated that diabetes-induced oxidative stress alters homeostasis of retinal nerve growth factor (NGF) resulting in accumulation of its precursor, proNGF, at the expense of NGF which plays a critical role in preserving neuronal and retinal function. This imbalance coincided with retinal damage in experimental diabetes. Here we test the hypothesis that alteration of proNGF and NGF levels observed in retina and vitreous will be mirrored in serum of diabetic patients. Blood and vitreous samples were collected from patients (diabetic and nondiabetic) undergoing vitrectomy at Georgia Regents University under approved IRB. Levels of proNGF, NGF, and p75(NTR) shedding were detected using Western blot analysis. MMP-7 activity was also assayed. Diabetes-induced proNGF expression and impaired NGF expression were observed in vitreous and serum. Vitreous and sera from diabetic patients (n = 11) showed significant 40.8-fold and 3.6-fold increases, respectively, compared to nondiabetics (n = 9). In contrast, vitreous and sera from diabetic patients showed significant 44% and 64% reductions in NGF levels, respectively, compared to nondiabetics. ProNGF to NGF ratios showed significant correlation between vitreous and serum. Further characterization of diabetes-induced imbalance in the proNGF to NGF ratio will facilitate its utility as an early biomarker for diabetic complications.

The role of dynamic indocyanine green angiography in the diagnosis and treatment of retinal angiomatous proliferation.

AIMS: We compared the effectiveness and durability of indocyanine green angiography (ICG) directed focal thermal laser treatment of the afferent arteriole in the treatment of retinal angiomatous proliferation (RAP). METHODS: Sixteen consecutive patients presenting with stage I or II RAP lesions underwent optical coherence tomography, fluorescein angiography and dynamic ICG examination and were evaluated for response to treatment. Two groups were evaluated: focal laser as initial treatment; and focal laser as salvage treatment after recurrence with photodynamic therapy (PDT) and intravitreal triamcinolone. Five additional eyes with stage III RAP were evaluated separately. RESULTS: Seven eyes received focal laser as initial treatment, and nine eyes received focal laser as salvage treatment after failure of PDT with triamcinolone. Five of seven eyes in the initial focal laser group demonstrated resolution of oedema. All five of the responders recurred (mean 4.4 months). Salvage therapy with PDT and triamcinolone after focal laser failure transiently closed these recurrences. In contrast, eight of nine eyes receiving thermal ablation of the RAP lesion after recurrence from prior PDT/triamcinolone demonstrated initial improvement of the retinal oedema. Four eyes demonstrated no recurrence within a year. None of the five eyes with stage III RAP improved anatomically or visually. CONCLUSION: Focal thermal laser treatment of RAP arteriole can resolve retinal oedema. However, durability was longer in eyes with prior PDT and triamcinolone treatment than those receiving thermal laser as initial therapy. These results suggest that focal laser may be useful in treatment of RAP recurrences and that combination therapy with PDT/triamcinolone plus focal laser is better than focal laser alone.