Sudden Reversible Osmotic Lens Damage ("Sugar Cracks") after Initiation of Metformin
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《新英格兰医药杂志》
To the Editor: We observed a unique type of ocular lens damage in a 62-year-old man with no history of ophthalmologic disease. He had a history of heart failure requiring five-vessel cardiac bypass surgery. He had polydipsia and polyuria, which became markedly aggravated after an overseas trip; on the patient's return, his primary care physician diagnosed diabetes mellitus (serum glucose level, 21.8 mmol per liter ; glycosylated hemoglobin level, 17.5 percent). Metformin (at a dose of 750 mg twice daily) reduced the serum glucose level to 14.6 mmol per liter (263 mg per deciliter) within four days and at a higher dose (850 mg twice daily) reduced the serum glucose level to 8.7 mmol per liter (157 mg per deciliter) over the ensuing week.
The patient distinctly remembered the sudden onset of blurry vision two days after the initiation of metformin therapy. Blurred vision led to his referral to our service two weeks after onset. At that time, the best corrected visual acuity was 20/80 in the right eye and 20/33 in the left eye. The intraocular pressure (17 to 19 mm Hg) was normal. Slit-lamp examination revealed multiple bilateral, crack-shaped lines traversing the lens (Figures 1A and 1B). These cracks were located primarily in the central part of the lens (nucleus), running more or less parallel to the nuclear curvature. In addition, a larger crack continued as a fairly straight band near both ends of the equator, seemingly traversing the nuclear lens fibers tangentially. These cracks had the same optical density as the aqueous in the anterior chamber, suggesting the presence of fluid-filled cavities within the lens. Other ophthalmic findings were unremarkable. Funduscopy revealed no signs of diabetic retinopathy.
Figure 1. "Sugar Cracks" (Lens Damage) due to Glucose Regulation.
Sugar cracks in the right eye (Panel A) and left eye (Panel B) and their spontaneous disappearance within four months (Panels C and D, right eye and left eye, respectively) are shown with the use of Scheimpflug slit-lamp lens photography.
Three months after the initiation of metformin therapy, the lens cracks had vanished spontaneously and visual acuity had improved (right eye, 20/40; left eye, 20/25). At the three-month mark, a trace subcapsular cataract was noted. Over the next two months, visual acuity was recovered (20/20 in both eyes), and no observable lens cracks or opacifications remained (Figures 1C and 1D). During follow-up, no changes were found in the anterior lens radius or refraction; serum glucose levels remained between 6 and 8 mmol per liter.
The lens findings, which we designated "sugar cracks," appeared to be directly related to the decrease in extracellular glucose levels. A toxic effect of metformin would seem to be unlikely.1 The optical density and the reversible nature of the lesions suggest that they were fluid-filled cavities within the interstitium of the lens nucleus, presumably caused by cell-volume regulation in response to hypotonic extracellular fluid. It seems far less likely that the lesions were caused by a rupture in the lens fiber as a result of osmotic swelling. The location of the lesions within the nucleus may be related to the interstitial circulation within the lens.2 This case suggests that adequate cell-volume regulation in the human lens, which has been shown to occur in the cortex,3,4 may also be present in the nuclear region.
Gijsbrecht J.M. Tangelder, M.D.
Michiel Dubbelman, Ph.D.
Peter J. Ringens, M.D., Ph.D.
VU University Medical Center
1007 MB Amsterdam, the Netherlands
g.tangelder@vumc.nl
References
Biguanide antidiabetics. In: Sweetman S, ed. Martindale, the complete drug reference. 33rd ed. London: Pharmaceutical Press, 2002:320-1.
Mathias RT, Rae JL, Baldo GJ. Physiological properties of the normal lens. Physiol Rev 1997;77:21-50.
Beebe DC, Parmelee JT, Belcher KS. Volume regulation in lens epithelial cells and differentiating lens fiber cells. J Cell Physiol 1990;143:455-459.
Diecke FP, Beyer-Mears A. A mechanism for regulatory volume decrease in cultured lens epithelial cells. Curr Eye Res 1997;16:279-288.
The patient distinctly remembered the sudden onset of blurry vision two days after the initiation of metformin therapy. Blurred vision led to his referral to our service two weeks after onset. At that time, the best corrected visual acuity was 20/80 in the right eye and 20/33 in the left eye. The intraocular pressure (17 to 19 mm Hg) was normal. Slit-lamp examination revealed multiple bilateral, crack-shaped lines traversing the lens (Figures 1A and 1B). These cracks were located primarily in the central part of the lens (nucleus), running more or less parallel to the nuclear curvature. In addition, a larger crack continued as a fairly straight band near both ends of the equator, seemingly traversing the nuclear lens fibers tangentially. These cracks had the same optical density as the aqueous in the anterior chamber, suggesting the presence of fluid-filled cavities within the lens. Other ophthalmic findings were unremarkable. Funduscopy revealed no signs of diabetic retinopathy.
Figure 1. "Sugar Cracks" (Lens Damage) due to Glucose Regulation.
Sugar cracks in the right eye (Panel A) and left eye (Panel B) and their spontaneous disappearance within four months (Panels C and D, right eye and left eye, respectively) are shown with the use of Scheimpflug slit-lamp lens photography.
Three months after the initiation of metformin therapy, the lens cracks had vanished spontaneously and visual acuity had improved (right eye, 20/40; left eye, 20/25). At the three-month mark, a trace subcapsular cataract was noted. Over the next two months, visual acuity was recovered (20/20 in both eyes), and no observable lens cracks or opacifications remained (Figures 1C and 1D). During follow-up, no changes were found in the anterior lens radius or refraction; serum glucose levels remained between 6 and 8 mmol per liter.
The lens findings, which we designated "sugar cracks," appeared to be directly related to the decrease in extracellular glucose levels. A toxic effect of metformin would seem to be unlikely.1 The optical density and the reversible nature of the lesions suggest that they were fluid-filled cavities within the interstitium of the lens nucleus, presumably caused by cell-volume regulation in response to hypotonic extracellular fluid. It seems far less likely that the lesions were caused by a rupture in the lens fiber as a result of osmotic swelling. The location of the lesions within the nucleus may be related to the interstitial circulation within the lens.2 This case suggests that adequate cell-volume regulation in the human lens, which has been shown to occur in the cortex,3,4 may also be present in the nuclear region.
Gijsbrecht J.M. Tangelder, M.D.
Michiel Dubbelman, Ph.D.
Peter J. Ringens, M.D., Ph.D.
VU University Medical Center
1007 MB Amsterdam, the Netherlands
g.tangelder@vumc.nl
References
Biguanide antidiabetics. In: Sweetman S, ed. Martindale, the complete drug reference. 33rd ed. London: Pharmaceutical Press, 2002:320-1.
Mathias RT, Rae JL, Baldo GJ. Physiological properties of the normal lens. Physiol Rev 1997;77:21-50.
Beebe DC, Parmelee JT, Belcher KS. Volume regulation in lens epithelial cells and differentiating lens fiber cells. J Cell Physiol 1990;143:455-459.
Diecke FP, Beyer-Mears A. A mechanism for regulatory volume decrease in cultured lens epithelial cells. Curr Eye Res 1997;16:279-288.