**Author details**

significant laboratory expertise. Evaluation of small fiber neuropathy is essential, as they constitute 70–90% of peripheral nerves and are preferentially involved in the development of diabetic peripheral neuropathy (DPN). DPN affects at least 50% of patients with diabetes mellitus and is the main initiating factor for foot ulceration and subsequent lower extremity amputation [143]. Unfortunately, to date, the guidelines for DPN mainly advocate electrophysiology besides clinical symptom testing, which is sensitive only for the detection of large fiber damage [144]. CCM could potentially serve as a non-invasive, objective biomarker for identifying small fiber damage and making an early diagnosis of DPN. The main changes in SNP morphology detected in patients with diabetes include a decrease in corneal nerve fiber density (CNFD), defined as the total number of major nerves per

; corneal nerve fiber length (CNFL), defined as the total length of all nerve fibers and

relationship between SNP morphology and the development and progression of DR. SNP impairment appears to progress in parallel with DR and could even be demonstrated in patients with diabetes without DR [146–149]. This finding would support the concept that besides neuronal loss in the retina, corneal neurodegeneration might precede the develop-

Even though recent studies indicate that inner retinal layer thinning representing retinal neurodegeneration is associated with DPN, the direct relation between SNP morphology and variables of retinal neurodegeneration has not yet been clarified. Eventually, CCM has the potential to be a surrogate for an early diagnosis of and an early biomarker for DR and DPN that could identify

Diabetes mellitus is clearly a major health problem in an increasingly aging population worldwide. Diabetic retinopathy is a complex complication of this disease, which is influenced by a range of local and systemic factors. Potential non-invasive biomarkers derived from innovative imaging modalities as introduced above offer precious information about the morphologic as well as functional state of the diabetic retina, which is not detectable on routine clinical examination. These promising biomarkers may allow personalized medicine with treatment schedules tailored to patients' individual needs. Furthermore, as the population principally affected by DR comprises working-age individuals, understanding of the pathophysiology of the disease and developing appropriate therapy are essential to halt decrease in productivity and an increasing need for social support. Besides this significant economic benefit, the final validation of these biomarkers in prospective studies is expected to contribute decisively to the designing of clinical trials to identify new drug candidates that may prevent DR in the initial disease stages. Finally, and most importantly, this could result in a dramatic quality-of-life improvement for patients with diabetes and

); and corneal nerve branch density (CNBD), defined as the number of

[145]. Previous studies have evaluated the

mm2

branches (mm/mm2

those at risk.

**6. Conclusions**

their families.

branches emanating from major nerves per mm2

24 Early Events in Diabetic Retinopathy and Intervention Strategies

ment of visible microangiopathy in DR too.

Julia Hafner\*, Sonja Karst and Ursula Schmidt-Erfurth

\*Address all correspondence to: julia.hafner@meduniwien.ac.at

Department of Ophthalmology and Optometry, Medical University of Vienna, Vienna, Austria
