Vision Science and Eye

Biography

Biography: Nilufer Koyluoglu

Abstract

INTRODUCTION

Over 382 million people in the World have diabetes, 46% of globally diabetes population is undiagnosed. Up to 50% of diabetes is detected with a clinical complication. Diabetic population will increase 54% while the number of ophthalmologists will increase by 2%. Will present activities address the magnitude of the issues that are coming up? This massive problem requires a high level solution. The average lag between onset and diagnosis of type 2 diabetes is 7 years. If diabetes cannot be prevented, the best way to ensure better patient outcomes is to detect early and manage continuously. Fortunately technological developments can make a significant difference in perception.

Advanced glycation end products (AGEs) are proteins that become glycated as a result of exposure to sugars. AGEs affect nearly every type of cell and molecule in the body. In the blood stream glucose sticks to the haemoglobin to make a 'glycosylated haemoglobin' molecule, called haemoglobin A1C (HbA1c) which is most recognised one among the large molecular family of AGEs. HbA1c is measured primarily to identify the three-month average plasma glucose concentration. The HbA1C test is currently one of the best ways to check diabetes is under control.

In a similar way fructosamine testing, typically reflect albumin glycation that is rarely used in clinical practice, because albumin has a half-life of approximately 20 days, the plasma fructosamine concentration reflects relatively recent (1-2 week) changes in blood glucose.

Although most proteins in living system turn over with sufficient rapidity to avoid signficant accumuation of AGEs, published evidence shows that with the appearance of glucose in the blood, glucose also appears in the aqueous humor of the eye and is subsequently transported within the crystalline lens. These glucose molecules are still “sticky,” with the same affinity for protein, including collagen within the lens. The non-enzymatic, chemical bonding between glucose and lens proteins forms irreversible glyco-protein aggregates. AGEs accumuate in these proteins over a persons lifetime.

Lens autoluorescence may have a clinical utility is suggested by its physiological basis, which is the accumulation of AGEs, a heterogenous family of yellow-brown and fluorescent proteins that have been modified by glycation.

MATHERIAL AND METHOD

Studies of the autoflurescence of the human crytalline lens have established that lens autofluorescence intensity increases with the age of the subject and that lens autofluorescence is further increased in patients with diabetes mellitus. Thus lens autofluorescence as a noninvasive measure of AGE accumulation, can be regarded as a measure of cumulative tissue damage due to elevated sugar in plasma and interstitial fluids. The clinical application of lens autofluorescence with a scanning confocal lens fluorescence biomicroscope enables the clinican to measure lens autofluorescence in routine examinations. Patients with lens fluorescence significantly higher then expected for their ages may have accelereted accumulation of AGEs and increased risk for the pathologies associated with diabetes and AGEs. AGEs throughout the body, including lenticular AGE’s, are higher in people with diabetes and pre-diabetes than the rest of the population. An interesting characteristic of AGE’s is that they will fluoresce when exposed to light, and the amount of fluorescence can be detected by an optical sensor. The transparency of the ocular media (cornea, aqueous and lens) provides a unique opportunity to shine an excitatory light source on fluorescent AGEs within the human lens and correlate that fluorescence with the degree of AGE deposition. The only technology available in the U.S. cleared by the U.S. Food and Drug Administration (FDA) for the non-invasive measurement of lens autofluorescence is the CLEARPATH DS-120™, manufactured by Freedom Meditech, Inc. (San Diego, CA). 

RESULTS

The CLEARPATH DS-120™ accurately measures a person’s lenticular fluorescence and reports if the result is at normal, high, or low limits versus age-adjusted normative data. Thus, since the glycation process in the lens has been reported to be irreversible, one can think of lens autofluorescence as a tool to obtain information about a person’s glucose excursions over a lifetime. Over 60 peer-reviewed published studies have shown a significant correlation between higher than average age-dependent lens autofluorescence, associated degenerative changes in the lens, and the presence of AGE’s, which are considered a hallmark of uncontrolled glucose. Patients with measurements above the 95% prediction interval should be referred by the clinician to primary care for a follow-on glycemic control evaluation. For patient’s whose measurements fall between the 80% and 95% prediction intervals, the clinician may decide to perform a clearpath evaluation annually to monitor if a patient’s fluorescence ratio moves up to the 95% prediction interval. Patients with an autofluorescence measure below the 80% prediction interval are suggested for a clearpath evaluation again in three years time. By placing a patients’s lens autofluorescence measure the clinician can identify patients with lens fluorescence that is higher than expected as red or orange line. Patients with measurements above the 95% prediction interval should be referred by the clinician to primary care for follow on glycemic control evalution. Above the red line means that is highly likely they will receive a differential diagnosis of prediabetes or diabetes. Orange colour code means the patient has higher than expected AGE accumulation again. It is likey they have had poor glucose control over their lifetime. Green line means the patient is likely within normal range and has had less than expected AGE accumulation, if the subject has diabetes, it is possible their glucose levels have been under good control such as diabetic patients with normal HbA1c. It is also possible the patient has latent autoimmune diabetes in adults or other metabolic issues such as pancreatitis, infections, and certain drugs maybe in green due short duration of out of control glucose. On the other side, lens autofluorescence measurement can identify patients with lens fluorescence lower than expected as under the green line. Thus fluorescein ratio provides information on the mobility of the person, the calories they get / the calories burned and
it should be investigated by further studies whether it will be an athletic performance indicator such as an athlete's pulse.

CONCLUSION

The clinical data indicated that the fluorescence ratio could provide better discrimination between individuals with and without diabetes than fluorescence intensity. This new parameter expresses metabolic control as longterm for patients with or without diabetes. Whereupon the crystalline lens has a new dimension which is providing information other than its own function related to visual function and cataract, as HbA1c that provides information other than haemoglobin’s own function If we think of fasting blood sugar and postprandial blood sugar as photograph, HbA1c as fragman, fluorescein ratio can be considered as whole film of life until cataract operation and it should be considered as a metabolic credit note of the person. Noninvasive measurements of lens autofluorescence may have clinical utility for general health beyond the diabetes and its complication.