Abstract

A simple, low-cost, portable instrument for measurement of the autofluorescence of the human cornea is presented. Corneal autofluorescence has proved to be strongly correlated with the grade of retinopathy in diabetic patients. It is therefore a reliable parameter for detection of different levels of diabetic retinopathy, thus permitting timely intervention by ophthalmologists. The instrument contains custom optics and electronics and exhibits excellent linearity and repeatability both in vitro and in vivo. Preliminary tests on volunteers show promise for its use in clinical practice.

© 1998 Optical Society of America

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  1. F. A. L’Esperance, W. A. James, “The problem of diabetic retinopathy,” in Diabetic Retinopathy, H. L. Little, R. L. Jack, A. Patz, P. H. Forham, eds. (Thieme-Stratton, New York, 1983), pp. 11–20.
  2. T. J. Merimee, “Diabetic retinopathy: a synthesis of perspectives,” N. Engl. J. Med. 322, 978–983 (1990).
    [CrossRef] [PubMed]
  3. J. C. Will, L. S. Geiss, S. F. Wetterhall, “Diabetic retinopathy,” N. Engl. J. Med. 323, 613–623 (1990).
    [CrossRef]
  4. G. M. Haik, W. L. Terrel, G. M. Haik, “Diabetic retinopathy: a leading cause of new blindness,” South. Med. J. 82, 575–579 (1989).
    [CrossRef] [PubMed]
  5. E. J. Sussman, W. G. Tsiaras, K. A. Soper, “Diagnosis of diabetic eye disease,” J. Am. Med. Assoc. 247, 3231–3234 (1982).
    [CrossRef]
  6. P. H. Gregson, Z. Shen, R. C. Scott, V. Kozousek, “Automated grading of venous beading,” Comput. Biomed. Res. 28, 291–304 (1995).
    [CrossRef] [PubMed]
  7. L. Rovati, F. Fankhauser, J. Ricka, “Design and performance of a new ophthalmic instrument for dynamic light scattering in the human eye,” Rev. Sci. Instrum. 67, 2615–2620 (1996).
    [CrossRef]
  8. T. R. Stolwijk, J. A. Van Best, J. A. Oosterhuis, W. Swart, “Corneal autofluorescence: an indicator of diabetic retinopathy,” Invest. Ophthalmol. Visual Sci. 33, 92–97 (1992).
  9. J. C. Bleeker, J. A. Van Best, L. Vrij, E. A. Van der Velde, J. A. Oosterhuis, “Autofluorescence of the lens in diabetic and healthy subjects by fluorophotometry,” Invest. Opthalmol. Visual Sci. 27, 791–794 (1986).
  10. T. R. Stolwijk, J. A. Van Best, J. P. Boot, J. A. Oosterhuis, “Corneal autofluorescence in diabetic and penetrating keratoplasty patients as measured by fluorophotometry,” Exp. Eye Res. 51, 403–409 (1990).
    [CrossRef] [PubMed]
  11. S. Janiec, M. Rzendkowski, S. Bolek, “The relation between corneal autofluorescence, endothelial cell count and severity of diabetic retinopathy,” Int. Ophthalmol. 18, 205–209 (1994).
    [CrossRef]
  12. S. Fantaguzzi, F. Docchio, L. Guarisco, R. Brancato, “Corneal autofluorescence in diabetic and normal eyes,” Int. Ophthalmol. 18, 211–214 (1994).
    [CrossRef] [PubMed]
  13. M. Ishida, N. Yokoi, J. Okuzawa, K. Maeda, S. Kinoshita, “Corneal autofluorescence in patients with diabetic retinopathy,” Nippon Ganka Gakkai Zasshi 99, 308–311 (1995) (in Japanese).
  14. H. J. Van Schaik, J. M. Benitez del Castillo, M.-J. Caubergh, A. Gobert, E. Leite, B. Moldow, V. Rosas, J. A. Van Best, “Screening diabetic retinopathy by fluorophotometry,” submitted to Exp. Eye Res.
  15. E. P. M. Boets, “Fluorophotometry of the anterior segment of the eye with special attention to contact lenses,” Ph.D. dissertation (Leiden State University, Leiden, The Netherlands, 1995), Chap. 5, pp. 48–68.
  16. B. R. Masters, “Noninvasive corneal redox fluorometry,” in Current Topics in Eye Research, J. Zadunaisky, H. Davson, eds. Academic, New York, (1984), Vol. 4, pp. 139–200.
  17. B. R. Masters, “In vivo corneal redox fluorometry,” in Noninvasive Diagnostic Techniques in Ophthalmology, B. R. Masters, ed. (Springer-Verlag, New York, (1990), pp. 223–247.
  18. A. G. Bennet, I. L. Francis, “The eye as an optical system,” in Visual Optics and the Optical Space Sense, H. Davson, ed., Vol. 4 of The Eye (Academic, New York, 1962), pp. 101–131.
  19. E. Alexandridis, Die Pupille, Physiologie-Untersuchung-Pathologie, K. Triltsch, ed. (Springer-Verlag, Berlin, 9–10 (1982), pp. 9–10.
  20. International Standard IEC 824:1984 and Its Amendment 1:1990, approved by CENELEC as EN 60825 (CENELEC, Brussels, 15March1991), Chap. 9, Table 1, pp. 42–55.
  21. E. M. Beems, J. A. Van Best, “Light transmission of the cornea in whole human eyes,” Exp. Eye Res. 50, 393–395 (1990).
    [CrossRef] [PubMed]
  22. H. J. Van Schaik, J. A. Van Best, “A solid fluorescence reference for corneal autofluorescence measurements,” Exp. Eye Res. 64, 121–123 (1997).
    [CrossRef] [PubMed]
  23. Diabetic Retinopathy Study Research Group, “A modification of the Airlie House classification of diabetic retinopathy,” Rep. 7, Invest. Ophthalmol. Visual Sci. 21, 219–226 (1981).

1997 (1)

H. J. Van Schaik, J. A. Van Best, “A solid fluorescence reference for corneal autofluorescence measurements,” Exp. Eye Res. 64, 121–123 (1997).
[CrossRef] [PubMed]

1996 (1)

L. Rovati, F. Fankhauser, J. Ricka, “Design and performance of a new ophthalmic instrument for dynamic light scattering in the human eye,” Rev. Sci. Instrum. 67, 2615–2620 (1996).
[CrossRef]

1995 (2)

P. H. Gregson, Z. Shen, R. C. Scott, V. Kozousek, “Automated grading of venous beading,” Comput. Biomed. Res. 28, 291–304 (1995).
[CrossRef] [PubMed]

M. Ishida, N. Yokoi, J. Okuzawa, K. Maeda, S. Kinoshita, “Corneal autofluorescence in patients with diabetic retinopathy,” Nippon Ganka Gakkai Zasshi 99, 308–311 (1995) (in Japanese).

1994 (2)

S. Janiec, M. Rzendkowski, S. Bolek, “The relation between corneal autofluorescence, endothelial cell count and severity of diabetic retinopathy,” Int. Ophthalmol. 18, 205–209 (1994).
[CrossRef]

S. Fantaguzzi, F. Docchio, L. Guarisco, R. Brancato, “Corneal autofluorescence in diabetic and normal eyes,” Int. Ophthalmol. 18, 211–214 (1994).
[CrossRef] [PubMed]

1992 (1)

T. R. Stolwijk, J. A. Van Best, J. A. Oosterhuis, W. Swart, “Corneal autofluorescence: an indicator of diabetic retinopathy,” Invest. Ophthalmol. Visual Sci. 33, 92–97 (1992).

1990 (4)

T. R. Stolwijk, J. A. Van Best, J. P. Boot, J. A. Oosterhuis, “Corneal autofluorescence in diabetic and penetrating keratoplasty patients as measured by fluorophotometry,” Exp. Eye Res. 51, 403–409 (1990).
[CrossRef] [PubMed]

T. J. Merimee, “Diabetic retinopathy: a synthesis of perspectives,” N. Engl. J. Med. 322, 978–983 (1990).
[CrossRef] [PubMed]

J. C. Will, L. S. Geiss, S. F. Wetterhall, “Diabetic retinopathy,” N. Engl. J. Med. 323, 613–623 (1990).
[CrossRef]

E. M. Beems, J. A. Van Best, “Light transmission of the cornea in whole human eyes,” Exp. Eye Res. 50, 393–395 (1990).
[CrossRef] [PubMed]

1989 (1)

G. M. Haik, W. L. Terrel, G. M. Haik, “Diabetic retinopathy: a leading cause of new blindness,” South. Med. J. 82, 575–579 (1989).
[CrossRef] [PubMed]

1986 (1)

J. C. Bleeker, J. A. Van Best, L. Vrij, E. A. Van der Velde, J. A. Oosterhuis, “Autofluorescence of the lens in diabetic and healthy subjects by fluorophotometry,” Invest. Opthalmol. Visual Sci. 27, 791–794 (1986).

1982 (1)

E. J. Sussman, W. G. Tsiaras, K. A. Soper, “Diagnosis of diabetic eye disease,” J. Am. Med. Assoc. 247, 3231–3234 (1982).
[CrossRef]

1981 (1)

Diabetic Retinopathy Study Research Group, “A modification of the Airlie House classification of diabetic retinopathy,” Rep. 7, Invest. Ophthalmol. Visual Sci. 21, 219–226 (1981).

Alexandridis, E.

E. Alexandridis, Die Pupille, Physiologie-Untersuchung-Pathologie, K. Triltsch, ed. (Springer-Verlag, Berlin, 9–10 (1982), pp. 9–10.

Beems, E. M.

E. M. Beems, J. A. Van Best, “Light transmission of the cornea in whole human eyes,” Exp. Eye Res. 50, 393–395 (1990).
[CrossRef] [PubMed]

Benitez del Castillo, J. M.

H. J. Van Schaik, J. M. Benitez del Castillo, M.-J. Caubergh, A. Gobert, E. Leite, B. Moldow, V. Rosas, J. A. Van Best, “Screening diabetic retinopathy by fluorophotometry,” submitted to Exp. Eye Res.

Bennet, A. G.

A. G. Bennet, I. L. Francis, “The eye as an optical system,” in Visual Optics and the Optical Space Sense, H. Davson, ed., Vol. 4 of The Eye (Academic, New York, 1962), pp. 101–131.

Bleeker, J. C.

J. C. Bleeker, J. A. Van Best, L. Vrij, E. A. Van der Velde, J. A. Oosterhuis, “Autofluorescence of the lens in diabetic and healthy subjects by fluorophotometry,” Invest. Opthalmol. Visual Sci. 27, 791–794 (1986).

Boets, E. P. M.

E. P. M. Boets, “Fluorophotometry of the anterior segment of the eye with special attention to contact lenses,” Ph.D. dissertation (Leiden State University, Leiden, The Netherlands, 1995), Chap. 5, pp. 48–68.

Bolek, S.

S. Janiec, M. Rzendkowski, S. Bolek, “The relation between corneal autofluorescence, endothelial cell count and severity of diabetic retinopathy,” Int. Ophthalmol. 18, 205–209 (1994).
[CrossRef]

Boot, J. P.

T. R. Stolwijk, J. A. Van Best, J. P. Boot, J. A. Oosterhuis, “Corneal autofluorescence in diabetic and penetrating keratoplasty patients as measured by fluorophotometry,” Exp. Eye Res. 51, 403–409 (1990).
[CrossRef] [PubMed]

Brancato, R.

S. Fantaguzzi, F. Docchio, L. Guarisco, R. Brancato, “Corneal autofluorescence in diabetic and normal eyes,” Int. Ophthalmol. 18, 211–214 (1994).
[CrossRef] [PubMed]

Caubergh, M.-J.

H. J. Van Schaik, J. M. Benitez del Castillo, M.-J. Caubergh, A. Gobert, E. Leite, B. Moldow, V. Rosas, J. A. Van Best, “Screening diabetic retinopathy by fluorophotometry,” submitted to Exp. Eye Res.

Docchio, F.

S. Fantaguzzi, F. Docchio, L. Guarisco, R. Brancato, “Corneal autofluorescence in diabetic and normal eyes,” Int. Ophthalmol. 18, 211–214 (1994).
[CrossRef] [PubMed]

Fankhauser, F.

L. Rovati, F. Fankhauser, J. Ricka, “Design and performance of a new ophthalmic instrument for dynamic light scattering in the human eye,” Rev. Sci. Instrum. 67, 2615–2620 (1996).
[CrossRef]

Fantaguzzi, S.

S. Fantaguzzi, F. Docchio, L. Guarisco, R. Brancato, “Corneal autofluorescence in diabetic and normal eyes,” Int. Ophthalmol. 18, 211–214 (1994).
[CrossRef] [PubMed]

Francis, I. L.

A. G. Bennet, I. L. Francis, “The eye as an optical system,” in Visual Optics and the Optical Space Sense, H. Davson, ed., Vol. 4 of The Eye (Academic, New York, 1962), pp. 101–131.

Geiss, L. S.

J. C. Will, L. S. Geiss, S. F. Wetterhall, “Diabetic retinopathy,” N. Engl. J. Med. 323, 613–623 (1990).
[CrossRef]

Gobert, A.

H. J. Van Schaik, J. M. Benitez del Castillo, M.-J. Caubergh, A. Gobert, E. Leite, B. Moldow, V. Rosas, J. A. Van Best, “Screening diabetic retinopathy by fluorophotometry,” submitted to Exp. Eye Res.

Gregson, P. H.

P. H. Gregson, Z. Shen, R. C. Scott, V. Kozousek, “Automated grading of venous beading,” Comput. Biomed. Res. 28, 291–304 (1995).
[CrossRef] [PubMed]

Guarisco, L.

S. Fantaguzzi, F. Docchio, L. Guarisco, R. Brancato, “Corneal autofluorescence in diabetic and normal eyes,” Int. Ophthalmol. 18, 211–214 (1994).
[CrossRef] [PubMed]

Haik, G. M.

G. M. Haik, W. L. Terrel, G. M. Haik, “Diabetic retinopathy: a leading cause of new blindness,” South. Med. J. 82, 575–579 (1989).
[CrossRef] [PubMed]

G. M. Haik, W. L. Terrel, G. M. Haik, “Diabetic retinopathy: a leading cause of new blindness,” South. Med. J. 82, 575–579 (1989).
[CrossRef] [PubMed]

Ishida, M.

M. Ishida, N. Yokoi, J. Okuzawa, K. Maeda, S. Kinoshita, “Corneal autofluorescence in patients with diabetic retinopathy,” Nippon Ganka Gakkai Zasshi 99, 308–311 (1995) (in Japanese).

James, W. A.

F. A. L’Esperance, W. A. James, “The problem of diabetic retinopathy,” in Diabetic Retinopathy, H. L. Little, R. L. Jack, A. Patz, P. H. Forham, eds. (Thieme-Stratton, New York, 1983), pp. 11–20.

Janiec, S.

S. Janiec, M. Rzendkowski, S. Bolek, “The relation between corneal autofluorescence, endothelial cell count and severity of diabetic retinopathy,” Int. Ophthalmol. 18, 205–209 (1994).
[CrossRef]

Kinoshita, S.

M. Ishida, N. Yokoi, J. Okuzawa, K. Maeda, S. Kinoshita, “Corneal autofluorescence in patients with diabetic retinopathy,” Nippon Ganka Gakkai Zasshi 99, 308–311 (1995) (in Japanese).

Kozousek, V.

P. H. Gregson, Z. Shen, R. C. Scott, V. Kozousek, “Automated grading of venous beading,” Comput. Biomed. Res. 28, 291–304 (1995).
[CrossRef] [PubMed]

L’Esperance, F. A.

F. A. L’Esperance, W. A. James, “The problem of diabetic retinopathy,” in Diabetic Retinopathy, H. L. Little, R. L. Jack, A. Patz, P. H. Forham, eds. (Thieme-Stratton, New York, 1983), pp. 11–20.

Leite, E.

H. J. Van Schaik, J. M. Benitez del Castillo, M.-J. Caubergh, A. Gobert, E. Leite, B. Moldow, V. Rosas, J. A. Van Best, “Screening diabetic retinopathy by fluorophotometry,” submitted to Exp. Eye Res.

Maeda, K.

M. Ishida, N. Yokoi, J. Okuzawa, K. Maeda, S. Kinoshita, “Corneal autofluorescence in patients with diabetic retinopathy,” Nippon Ganka Gakkai Zasshi 99, 308–311 (1995) (in Japanese).

Masters, B. R.

B. R. Masters, “Noninvasive corneal redox fluorometry,” in Current Topics in Eye Research, J. Zadunaisky, H. Davson, eds. Academic, New York, (1984), Vol. 4, pp. 139–200.

B. R. Masters, “In vivo corneal redox fluorometry,” in Noninvasive Diagnostic Techniques in Ophthalmology, B. R. Masters, ed. (Springer-Verlag, New York, (1990), pp. 223–247.

Merimee, T. J.

T. J. Merimee, “Diabetic retinopathy: a synthesis of perspectives,” N. Engl. J. Med. 322, 978–983 (1990).
[CrossRef] [PubMed]

Moldow, B.

H. J. Van Schaik, J. M. Benitez del Castillo, M.-J. Caubergh, A. Gobert, E. Leite, B. Moldow, V. Rosas, J. A. Van Best, “Screening diabetic retinopathy by fluorophotometry,” submitted to Exp. Eye Res.

Okuzawa, J.

M. Ishida, N. Yokoi, J. Okuzawa, K. Maeda, S. Kinoshita, “Corneal autofluorescence in patients with diabetic retinopathy,” Nippon Ganka Gakkai Zasshi 99, 308–311 (1995) (in Japanese).

Oosterhuis, J. A.

T. R. Stolwijk, J. A. Van Best, J. A. Oosterhuis, W. Swart, “Corneal autofluorescence: an indicator of diabetic retinopathy,” Invest. Ophthalmol. Visual Sci. 33, 92–97 (1992).

T. R. Stolwijk, J. A. Van Best, J. P. Boot, J. A. Oosterhuis, “Corneal autofluorescence in diabetic and penetrating keratoplasty patients as measured by fluorophotometry,” Exp. Eye Res. 51, 403–409 (1990).
[CrossRef] [PubMed]

J. C. Bleeker, J. A. Van Best, L. Vrij, E. A. Van der Velde, J. A. Oosterhuis, “Autofluorescence of the lens in diabetic and healthy subjects by fluorophotometry,” Invest. Opthalmol. Visual Sci. 27, 791–794 (1986).

Ricka, J.

L. Rovati, F. Fankhauser, J. Ricka, “Design and performance of a new ophthalmic instrument for dynamic light scattering in the human eye,” Rev. Sci. Instrum. 67, 2615–2620 (1996).
[CrossRef]

Rosas, V.

H. J. Van Schaik, J. M. Benitez del Castillo, M.-J. Caubergh, A. Gobert, E. Leite, B. Moldow, V. Rosas, J. A. Van Best, “Screening diabetic retinopathy by fluorophotometry,” submitted to Exp. Eye Res.

Rovati, L.

L. Rovati, F. Fankhauser, J. Ricka, “Design and performance of a new ophthalmic instrument for dynamic light scattering in the human eye,” Rev. Sci. Instrum. 67, 2615–2620 (1996).
[CrossRef]

Rzendkowski, M.

S. Janiec, M. Rzendkowski, S. Bolek, “The relation between corneal autofluorescence, endothelial cell count and severity of diabetic retinopathy,” Int. Ophthalmol. 18, 205–209 (1994).
[CrossRef]

Scott, R. C.

P. H. Gregson, Z. Shen, R. C. Scott, V. Kozousek, “Automated grading of venous beading,” Comput. Biomed. Res. 28, 291–304 (1995).
[CrossRef] [PubMed]

Shen, Z.

P. H. Gregson, Z. Shen, R. C. Scott, V. Kozousek, “Automated grading of venous beading,” Comput. Biomed. Res. 28, 291–304 (1995).
[CrossRef] [PubMed]

Soper, K. A.

E. J. Sussman, W. G. Tsiaras, K. A. Soper, “Diagnosis of diabetic eye disease,” J. Am. Med. Assoc. 247, 3231–3234 (1982).
[CrossRef]

Stolwijk, T. R.

T. R. Stolwijk, J. A. Van Best, J. A. Oosterhuis, W. Swart, “Corneal autofluorescence: an indicator of diabetic retinopathy,” Invest. Ophthalmol. Visual Sci. 33, 92–97 (1992).

T. R. Stolwijk, J. A. Van Best, J. P. Boot, J. A. Oosterhuis, “Corneal autofluorescence in diabetic and penetrating keratoplasty patients as measured by fluorophotometry,” Exp. Eye Res. 51, 403–409 (1990).
[CrossRef] [PubMed]

Sussman, E. J.

E. J. Sussman, W. G. Tsiaras, K. A. Soper, “Diagnosis of diabetic eye disease,” J. Am. Med. Assoc. 247, 3231–3234 (1982).
[CrossRef]

Swart, W.

T. R. Stolwijk, J. A. Van Best, J. A. Oosterhuis, W. Swart, “Corneal autofluorescence: an indicator of diabetic retinopathy,” Invest. Ophthalmol. Visual Sci. 33, 92–97 (1992).

Terrel, W. L.

G. M. Haik, W. L. Terrel, G. M. Haik, “Diabetic retinopathy: a leading cause of new blindness,” South. Med. J. 82, 575–579 (1989).
[CrossRef] [PubMed]

Tsiaras, W. G.

E. J. Sussman, W. G. Tsiaras, K. A. Soper, “Diagnosis of diabetic eye disease,” J. Am. Med. Assoc. 247, 3231–3234 (1982).
[CrossRef]

Van Best, J. A.

H. J. Van Schaik, J. A. Van Best, “A solid fluorescence reference for corneal autofluorescence measurements,” Exp. Eye Res. 64, 121–123 (1997).
[CrossRef] [PubMed]

T. R. Stolwijk, J. A. Van Best, J. A. Oosterhuis, W. Swart, “Corneal autofluorescence: an indicator of diabetic retinopathy,” Invest. Ophthalmol. Visual Sci. 33, 92–97 (1992).

T. R. Stolwijk, J. A. Van Best, J. P. Boot, J. A. Oosterhuis, “Corneal autofluorescence in diabetic and penetrating keratoplasty patients as measured by fluorophotometry,” Exp. Eye Res. 51, 403–409 (1990).
[CrossRef] [PubMed]

E. M. Beems, J. A. Van Best, “Light transmission of the cornea in whole human eyes,” Exp. Eye Res. 50, 393–395 (1990).
[CrossRef] [PubMed]

J. C. Bleeker, J. A. Van Best, L. Vrij, E. A. Van der Velde, J. A. Oosterhuis, “Autofluorescence of the lens in diabetic and healthy subjects by fluorophotometry,” Invest. Opthalmol. Visual Sci. 27, 791–794 (1986).

H. J. Van Schaik, J. M. Benitez del Castillo, M.-J. Caubergh, A. Gobert, E. Leite, B. Moldow, V. Rosas, J. A. Van Best, “Screening diabetic retinopathy by fluorophotometry,” submitted to Exp. Eye Res.

Van der Velde, E. A.

J. C. Bleeker, J. A. Van Best, L. Vrij, E. A. Van der Velde, J. A. Oosterhuis, “Autofluorescence of the lens in diabetic and healthy subjects by fluorophotometry,” Invest. Opthalmol. Visual Sci. 27, 791–794 (1986).

Van Schaik, H. J.

H. J. Van Schaik, J. A. Van Best, “A solid fluorescence reference for corneal autofluorescence measurements,” Exp. Eye Res. 64, 121–123 (1997).
[CrossRef] [PubMed]

H. J. Van Schaik, J. M. Benitez del Castillo, M.-J. Caubergh, A. Gobert, E. Leite, B. Moldow, V. Rosas, J. A. Van Best, “Screening diabetic retinopathy by fluorophotometry,” submitted to Exp. Eye Res.

Vrij, L.

J. C. Bleeker, J. A. Van Best, L. Vrij, E. A. Van der Velde, J. A. Oosterhuis, “Autofluorescence of the lens in diabetic and healthy subjects by fluorophotometry,” Invest. Opthalmol. Visual Sci. 27, 791–794 (1986).

Wetterhall, S. F.

J. C. Will, L. S. Geiss, S. F. Wetterhall, “Diabetic retinopathy,” N. Engl. J. Med. 323, 613–623 (1990).
[CrossRef]

Will, J. C.

J. C. Will, L. S. Geiss, S. F. Wetterhall, “Diabetic retinopathy,” N. Engl. J. Med. 323, 613–623 (1990).
[CrossRef]

Yokoi, N.

M. Ishida, N. Yokoi, J. Okuzawa, K. Maeda, S. Kinoshita, “Corneal autofluorescence in patients with diabetic retinopathy,” Nippon Ganka Gakkai Zasshi 99, 308–311 (1995) (in Japanese).

Comput. Biomed. Res. (1)

P. H. Gregson, Z. Shen, R. C. Scott, V. Kozousek, “Automated grading of venous beading,” Comput. Biomed. Res. 28, 291–304 (1995).
[CrossRef] [PubMed]

Exp. Eye Res. (3)

T. R. Stolwijk, J. A. Van Best, J. P. Boot, J. A. Oosterhuis, “Corneal autofluorescence in diabetic and penetrating keratoplasty patients as measured by fluorophotometry,” Exp. Eye Res. 51, 403–409 (1990).
[CrossRef] [PubMed]

E. M. Beems, J. A. Van Best, “Light transmission of the cornea in whole human eyes,” Exp. Eye Res. 50, 393–395 (1990).
[CrossRef] [PubMed]

H. J. Van Schaik, J. A. Van Best, “A solid fluorescence reference for corneal autofluorescence measurements,” Exp. Eye Res. 64, 121–123 (1997).
[CrossRef] [PubMed]

Int. Ophthalmol. (2)

S. Janiec, M. Rzendkowski, S. Bolek, “The relation between corneal autofluorescence, endothelial cell count and severity of diabetic retinopathy,” Int. Ophthalmol. 18, 205–209 (1994).
[CrossRef]

S. Fantaguzzi, F. Docchio, L. Guarisco, R. Brancato, “Corneal autofluorescence in diabetic and normal eyes,” Int. Ophthalmol. 18, 211–214 (1994).
[CrossRef] [PubMed]

Invest. Ophthalmol. Visual Sci. (1)

T. R. Stolwijk, J. A. Van Best, J. A. Oosterhuis, W. Swart, “Corneal autofluorescence: an indicator of diabetic retinopathy,” Invest. Ophthalmol. Visual Sci. 33, 92–97 (1992).

Invest. Opthalmol. Visual Sci. (1)

J. C. Bleeker, J. A. Van Best, L. Vrij, E. A. Van der Velde, J. A. Oosterhuis, “Autofluorescence of the lens in diabetic and healthy subjects by fluorophotometry,” Invest. Opthalmol. Visual Sci. 27, 791–794 (1986).

J. Am. Med. Assoc. (1)

E. J. Sussman, W. G. Tsiaras, K. A. Soper, “Diagnosis of diabetic eye disease,” J. Am. Med. Assoc. 247, 3231–3234 (1982).
[CrossRef]

N. Engl. J. Med. (2)

T. J. Merimee, “Diabetic retinopathy: a synthesis of perspectives,” N. Engl. J. Med. 322, 978–983 (1990).
[CrossRef] [PubMed]

J. C. Will, L. S. Geiss, S. F. Wetterhall, “Diabetic retinopathy,” N. Engl. J. Med. 323, 613–623 (1990).
[CrossRef]

Nippon Ganka Gakkai Zasshi (1)

M. Ishida, N. Yokoi, J. Okuzawa, K. Maeda, S. Kinoshita, “Corneal autofluorescence in patients with diabetic retinopathy,” Nippon Ganka Gakkai Zasshi 99, 308–311 (1995) (in Japanese).

Rep. 7, Invest. Ophthalmol. Visual Sci. (1)

Diabetic Retinopathy Study Research Group, “A modification of the Airlie House classification of diabetic retinopathy,” Rep. 7, Invest. Ophthalmol. Visual Sci. 21, 219–226 (1981).

Rev. Sci. Instrum. (1)

L. Rovati, F. Fankhauser, J. Ricka, “Design and performance of a new ophthalmic instrument for dynamic light scattering in the human eye,” Rev. Sci. Instrum. 67, 2615–2620 (1996).
[CrossRef]

South. Med. J. (1)

G. M. Haik, W. L. Terrel, G. M. Haik, “Diabetic retinopathy: a leading cause of new blindness,” South. Med. J. 82, 575–579 (1989).
[CrossRef] [PubMed]

Other (8)

F. A. L’Esperance, W. A. James, “The problem of diabetic retinopathy,” in Diabetic Retinopathy, H. L. Little, R. L. Jack, A. Patz, P. H. Forham, eds. (Thieme-Stratton, New York, 1983), pp. 11–20.

H. J. Van Schaik, J. M. Benitez del Castillo, M.-J. Caubergh, A. Gobert, E. Leite, B. Moldow, V. Rosas, J. A. Van Best, “Screening diabetic retinopathy by fluorophotometry,” submitted to Exp. Eye Res.

E. P. M. Boets, “Fluorophotometry of the anterior segment of the eye with special attention to contact lenses,” Ph.D. dissertation (Leiden State University, Leiden, The Netherlands, 1995), Chap. 5, pp. 48–68.

B. R. Masters, “Noninvasive corneal redox fluorometry,” in Current Topics in Eye Research, J. Zadunaisky, H. Davson, eds. Academic, New York, (1984), Vol. 4, pp. 139–200.

B. R. Masters, “In vivo corneal redox fluorometry,” in Noninvasive Diagnostic Techniques in Ophthalmology, B. R. Masters, ed. (Springer-Verlag, New York, (1990), pp. 223–247.

A. G. Bennet, I. L. Francis, “The eye as an optical system,” in Visual Optics and the Optical Space Sense, H. Davson, ed., Vol. 4 of The Eye (Academic, New York, 1962), pp. 101–131.

E. Alexandridis, Die Pupille, Physiologie-Untersuchung-Pathologie, K. Triltsch, ed. (Springer-Verlag, Berlin, 9–10 (1982), pp. 9–10.

International Standard IEC 824:1984 and Its Amendment 1:1990, approved by CENELEC as EN 60825 (CENELEC, Brussels, 15March1991), Chap. 9, Table 1, pp. 42–55.

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Figures (9)

Fig. 1
Fig. 1

(a) Layout of the portable corneal fluorometer for diagnosis of the level of DR. (b) General view of the optical head (to scale). Excitation light from the blue LED’s passes the excitation filters and illuminates the cornea tangentially via both prisms. A fixed part of the fluorescing cornea is imaged onto the sensitive area of the PMT via the emission filters, the camera lens, and a rectangular aperture in front of the PMT. The red LED in front of the cornea is used to constrict the pupil and to mask the human lens to prevent interference by lenticular fluorescence. The IR LED and the corresponding IR photodiode are used to yield a fixed distance between instrument and cornea, and a ring of 10 green LED’s (5 are shown) illuminates the cornea during focusing of the eye.

Fig. 2
Fig. 2

(a) Detailed top view of the fluorometer (to scale). Excitation light from the blue LED’s illuminates the cornea tangentially. A fixed part of the fluorescing cornea is depicted on the sensitive area of the PMT (dashed curves) as a result of the rectangular aperture before the PMT and the shadowing of the red LED in front of the cornea (hatched area). Note the shadowing of the human lens by the red LED and the constricted pupil. (b) Detailed front view (to scale). The corneal autofluorescence is excited by tangential illumination via both prisms. The fluorescence of the hatched rectangle is imaged on the sensitive area of the PMT. The ring of 10 green LED’s illuminates the cornea during focusing of the eye.

Fig. 3
Fig. 3

Spectral characteristics of excitation and detection. Upper curves: dotted curve, relative light power of a blue LED; left-hand thin solid curve, transmittance of the excitation filter combination used; right-hand thin solid curve, transmittance of the emission filter combination; thick solid curve, relative excitation light power. Lower curves, calculated total transmittance of all excitation and emission filters together. Note the large rejection (>108) of excitation light reflected by the cornea for the total spectral range. The spectral transmittance of each filter was measured separately with a spectrophotometer.

Fig. 4
Fig. 4

Electronics. Block diagram of the electronics for the acquisition and elaboration of the fluorescence signal and for the control of the measurement sequence.

Fig. 5
Fig. 5

Temporal diagram of the acquisition sequence. A–B, waiting; B–C, patient adjusting; C–D, 16 consecutive measurements, each consisting of a fluorescence measurement (0.2 s), a background measurement (0.2 s), and pupil constriction (0.2 s). Total duration of measurement, ∼13 s. D–A, computing data and display of results.

Fig. 6
Fig. 6

Distance accuracy. Plot of the IR receiver output as a function of the position of a glass cuvette with respect to the optical head. The center of the beam is at 330 μm and corresponds to the front surfaces of the prisms.

Fig. 7
Fig. 7

Linearity and accuracy. Plots of average fluorescence values (solid curve, left scale) and standard deviation (dashed curve, right scale) as a function of the concentration of NaFl in a cuvette.

Fig. 8
Fig. 8

Spatial sensitivity plot for corneal fluorescence. Fluorescence intensity signal at the output of the PMT of a solid sphere of polysterene-embedded NaFl of 1-mm diameter, moved in the XYZ direction. (0, 0, 0) is the front position of the red LED. The NaFl concentration of the sphere was ∼800 ng mL-1. (a) Movement in the X direction (left to right) at the position of the cornea (Z = 2 mm). (b) Movement in the Y direction (upward) at the same position. (c) Movement in the Z direction (along the optical axis of the instrument). Note the different intensity scales.

Fig. 9
Fig. 9

Preliminary results. Comparison of the corneal fluorometer and a commercial scanning fluorophotometer (Fluorotron Master). Open squares, healthy volunteers; filled symbols, diabetic patients with different grades of retinopathy (squares, no or negligible retinopathy; diamonds, background retinopathy; circles, (pre)proliferative retinopathy). The solid curve was obtained by linear regression to the data points, and the dotted curves represent the 95% probability limits for the regression line.

Tables (1)

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Table 1 Classification of Light Sources in Relation to Safety

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