We examine the lens for cataract in all patients, but it may provide an even greater snapshot of diseases elsewhere in the body.
The human lens is one of the few structures that continues to grow throughout our lifetime. As it does, it accumulates deposits that could alert practitioners to diagnose a systemic disease—not just connective tissue disorders like Weill-Marchesani syndrome in patients with microspherophakia or subluxated lenses in Marfan’s syndrome, but further-reaching diseases such as Alzheimer’s and diabetes mellitus.1
Alzheimer’s Disease (AD)
An accumulation of amyloid beta plaques in the brain results in neurological effects for patients with AD. An imaging technique currently in phase II of FDA clinical trials can detect these amyloid plaques within the crystalline lens.
The technique begins with a fluorescent ligand marker applied topically in an ointment to the inner corner of one eyelid. The application is done three separate times, two hours apart, the night before Sapphire II laser imaging (Cognoptix).
For imaging, the patient fixates on a target and a low-level laser allows for fluorescent measurements of the lens, providing a score relative to the level of amyloid detected. The entire procedure takes only a few minutes with imaging equipment the size of a personal computer. This technology could be beneficial to the diagnosis of AD, but perhaps even more critical in the clinical trials of potential AD therapies. A drug that results in amyloid deposition deceleration in the lens may also show reduction of deposition in the brain. Further research is certainly warranted.
Diabetes Mellitus (DM)
Advanced glycation end products (AGEs) are lipids or proteins that become gylcated after being exposed to sugars. They are prevalent in the blood vessels of patients with diabetes, but can also contribute to lens changes as they non-enzymatically bond to the lens proteins. Although AGEs form with natural aging, the process is accelerated by hyperglycemia and thus observed sooner in DM.
The glycation or condensation of the aldehyde and ketone groups in sugars with the amino groups in proteins also leads to a Schiff base—the initial step in the formation of cataracts—and this also may be detected via autofluorescence. Although lens autofluorescence increases with age, the greater levels of fluorophores can be differentiated in diabetic disease diagnosis. This can be captured through a scanning confocal lens fluorescence biomicroscope called the ClearPath DS-120 (Freedom Meditech), which received FDA premarket clearance this year. The test is non-invasive and takes about six seconds, as the patient simply places their chin in a chin rest and looks at a target.
A study of 127 subjects between the ages of 21 and 70 showed a linear model for lens autofluorescence intensity with age that was highly statistically significant.2 Multiple research studies have shown an increase in lens autofluorescence in patients with diabetes.3,4 Decades-old studies show this correlation, and only recently has technology become available for optometrists to measure it accurately.7,8
Statistical findings can also be obtained in both young and elderly patients with diabetes and in patients with early and late onset diabetes.7,8
Not only does autofluorescence of the lens help make a diagnosis of diabetes, but it can also correlate to the level of HbA1c. In one study comparing insulin-dependent diabetics with high HbA1c to another group with low HbA1c, the group with low HbA1c during the disease period showed significantly lower lens fluorescence.9 Furthermore, lens autofluorescence provides information about long-term control of the disease, as research shows it can be delayed by good metabolic control.10 A1c measures give a snapshot of the last two to three months in a diabetes patient, whereas lens autofluorescence measures the lifetime.
Another correlation exists with diabetic nephropathy, as one study compared 10 patients with diabetes and kidney disease to 11 otherwise comparable patients with diabetes without kidney disease. The patients with diabetic nephropathy had significantly greater lens autofluorescence measurements and decreased lens transmittance.11
What makes autofluorescence of the lens even more compelling is that it can support early diagnosis. In one 14-year follow-up study, which confirmed that lens fluorescence was significantly related to mean HbA1c, researchers noted that although fluorophore accumulation in the lens of a diabetes patient was increased in proportion to glycemic control, it was not sufficient to explain the entire variation. Thus, lens fluorescence must be influenced by other factors before initiation and during the study. The study authors further concluded that it may have been affected before the onset of DM.12 The underlying mechanism could be a variation in susceptibility to lens protein denaturation by glycation. This means that patients who are more likely to develop diabetes may have the initial effects noted in their crystalline lens.
The ability to make a diagnosis of AD or DM via the crystalline lens prior to clinical diagnosis or symptoms could solidify our role as primary eye care providers and help save the vision and lives of our patients.
1. Chu BS. Weill-Marchesani syndrome and secondary glaucoma associated with ectopia lentis. Clin Exp Optom. 2006 Mar;89(2):95-9.
2. Burd J, Stephen L, Cahn F et al. Simultaneous Noninvasive Clinical Measurement of Lens Autofluorescence and Rayleigh Scattering Using a Fluorescence Biomicroscope. J Diabetes Sci Technol. 2012 Nov 1;6(6):1251-9.
3. Bleeker JC, van Best JA, Vrij L, van der Velde EA, Oosterhuis JA. Autofluorescence of the lens in diabetic and healthy subjects by fluorophotometry. Invest Ophthalmol Vis Sci. 1986 May;27(5):791-4.
4. Kessel L, Sander B, Dalgaard P, Larsen M. Lens fluorescence and metabolic control in type 1 diabetic patients: a 14 year follow up study. Br J Ophthalmol. 2004 Sep;88(9):1169-72.
5. Van Best JA, Vrij L, Oosterhuis JA. Lens transmission of blue-green light in diabetic patients as measured by autofluorophotometry. Invest Ophthalmol Vis Sci. 1985 Apr;26(4):532-6.
6. Mosier MA, Occhipinti JR, Burstein NL. Autofluorescence of the crystalline lens in diabetes. Arch Ophthalmol. 1986 Sep;104(9):1340-3.
7. Van Wirdum E, van Best J, Bruining GJ, et al. Blood-retinal and blood-aqueous barrier permeability, lens autofluorescence and transmission in insulin-dependent diabetic youngsters. Graefes Arch Clin Exp Ophthalmol. 1989;227(1):26-9.
8. Moseir MA, Occhipinti JR, Burstein NL. Autofluorescence of the crystalline lens in diabetes. Arch Ophthalmol. 1986 Sep;104(9):1340-3.
9. Kjer B, Larsen M, Bendtson I et al. Lens autofluorescence in the diabetes compared with the level of glycosylated hemoglobin A1c. Acta Ophthalmol Suppl.1987;182:100-2.
10. Larsen M, Kjer B, Bendtson I, et al. Lens fluorescence in relation to metabolic control of insulin-dependent diabetes mellitus. Arch Ophthalmol.1989 Jan;107(1):59-62.
11. Larsen M, Kjer B, Bendtson I, et al. Lens fluorescence in relation to nephropathy in insulin-dependent diabetes mellitus. Graefes Arch Clin Exp Ophthalmol. 1992;230(1):6-10.
12. Kessel L, Sander B, Dalgaard P, Larsen M. Lens fluorescence and metabolic control in type 1 diabetic patients: a 14 year follow up study. Br J Ophthalmol. 2004 Sep;88(9):1169-72.