- Email: [email protected]
Human sclera: Thickness and surface area
Human
Sclera: Thickness
and Surface Area
TIMOTHY W. OLSEN, MD, SARAH Y. AABERG, DAYLE H. GEROSKI, PHD, AND HENRY F. EDELHAUSER, PHD PURPOSE: To assess the mean thickness and surface area of human sclera. l METHODS: Fifty-five formalin-fixed eye bank eyes were hemisected from anterior to posterior. Cross-sectional slides were taken to include a millimeter scale ruler in each photograph. Slide photographs were projected and the scleral silhouette sketched. Mean scleral thickness measurements with standard deviation were obtained. Twenty-five human eye bank eyes were used to determine total scleral surface area by either a computerized tracing method ( 17 globes) or vole umetric calculations (eight globes) using fluid displacement. l RESULTS: Mean scleral thickness f SD was 0.53 f 0.14 mm at the corneoscleral limbus, significantly decreasing to 0.39 f 0.17 mm near the equator, and increasing to 0.9 to 1.0 mm near the optic nerve. The mean total scleral surface area by surface area computerized tracings was 16.3 2 1.8 cm2 and, by the volume displacement method, was 17.0 2 1.5 cm*. l CONCLUSIONS: Scleral thickness and surface area measurements from cadaver eyes are important for ophthalmic surgeons and have implications for transscleral diffusion. l
Accepted for publication July 2, 1997. From the Department of Ophthalmology, Emory University, Atlanta, Georgia (Drs Olsen, Geroski, and Edelhauser, and MS Aaberg), and the University of Wisconsin, Madison, and William S. Middleton Memorial Veterans Hospital, Madison, Wisconsin (Dr Olsen). Supported in part by a Fellowship Award (Dr Olsen) from the Heed/Knapp Ophthalmic Foundation, Cleveland, Ohio; core grant P30 EY06360 from the National Eye Institute, Bethesda, Maryland; and an unrestricted grant from Research to Prevent Blindness, Inc, New York, New York (Dr Olsen). Dr Edelhauser is a Research to Prevent Blindness Senior Scholar. Some data from this study are presented as preliminary data in Tasman W, Jaeger EA, editors, Duane’s Foundations of Clinical Ophthalmology, Philadelphia: Lippincott-Raven, 1995. Reprint requests to Timothy W. Olsen, PhD, F4/336 Clinical Science Center, 600 Highland Ave, Madison, WI 53792-3220; fax: (608) 263-1466; e-mail: [email protected]
VOL.
125,
No.
2
0
AMERICAN
JOURNAL
S
CLERAL
DIMENSIONS
ARE
IMPORTANT
BOTH
SURGI-
tally and physiologically. Ophthalmic surgeons frequently perform lamellar dissections of the sclera or pass sutures at various depths within the scleral stroma at different locations on the globe. A precise measurement of scleral thickness and variability of thickness from the corneoscleral limbus to the optic nerve represents critical information for ophthalmic surgeons. Data on scleral thickness measurements are limited and mostly originate from the work of Stilling in 1905.’ Our current emphasis of scleral physiology is focused on transscleral permeability. Permeability is important because fluid and solute flow both out of the globe (that is, uveoscleral outflow) and into the globe (that is, transscleral drug delivery). Two important measurements of human scleral permeability are the total scleral surface area and scleral thickness. We previously demonstrated the relationship of scleral thickness and permeability to compounds varying in molecular weight.’ Additionally, permeability is directly related to flux or the amount of solute crossing a plane of unit surface area, which is normal (perpendicular) to the d’irection of transport per unit of time.3 Determination of transscleral drug delivery necessitates an accurate assessment of regional scleral thickness and total surface area of the human eye. The purpose of this report is to summarize the measurements of scleral thickness and surface area in human eye bank eyes.
METHODS FIFTY-FIVE
EYE
BANK
EYES
WERE
OBTAINED
FROM
THE
Georgia Eye Bank Inc (Atlanta, Georgia), stored in a moist chamber for 3 to 8 days postmortem, then fixed in 10% buffered formalin. Eyes were sectioned from
OF OPHTHALMOLOGY
1998;125:237-241
237
FIGURE 1. Human globe after fixation and transection. The lighting highlights the scleral edge and thick ness. Thi s is a globe with average scleral thickness. A millimeter scale is present inferiorly.
the center of the cornea through the globe in an anterior to posterior direction toward the macular area. The section was directed toward the macular area in order to transect the greater anterior-posterior circle of the eye. The sectioning technique did not consistently incorporate the thin area immediately under the rectus muscle. A high-resolution color slide photograph was taken of the entire globe, perpendicular to the cut edge of the sclera (Figures 1 and 2). A millimeter scale was photographed concomitantly. Photographic slides of sectioned sclera were then projected onto a sheet of paper placed on a solid white tracing screen. Projection distances were adjusted so that 1 mm on the ruler corresponded precisely to 1 cm on the projected image. The scleral silhouette was carefully traced on the paper screen. Perpendicular thickness measurements of the enlarged cut edge were measured using calipers (accurate to 0.05 mm) at every centimeter from the limbus posteriorly toward the optic nerve. These measurements corresponded to measurements taken at l-mm increments on the globe itself. Measurements were converted from centi238
AMERICAN
JOURNAL
meters to millimeters and averaged, and a standard deviation was calculated. To ensure the precision of the scleral measurements, one scleral section was randomly selected, and 10 different measurements of the same site on this section were taken of the posterior sclera near the optic nerve. The projected sclera was traced, and the demarcated region was measured exactly as all other sections. The slide was then removed from the projector, the projector was defocused, and the measurement was repeated 10 times. In another series of experiments, the globe from human donor eyes was inflated to 15 mm Hg by infusing balanced saline solution through the optic nerve. Using a needle through the optic nerve and a ligature, intraocular pressure was maintained at 15 mm Hg and confirmed with pnuemotonometry. Scleral thickness was then measured with an ultrasonic pachymeter. Seventeen fresh eye bank eyes (3 to 8 days postmortem) stored in moist chamber containers we?: used for surface area measurements. Eyes were not OF OPHTHALMOLOGY
FEBRUARY
I 998
FIGURE 2. Human globe after fixation and transection. millimeter scale is present inferiorly.
The cut edge demonstrates
fixed. They were transected at the equator with a razor blade. An anterior-posterior sharp incision was made in the two hemisections, both anteriorly (into the cornea) and posteriorly (into the optic nerve). The corneas were removed at the surgical limbus using a no. 69 blade and corneoscleral scissors. Posteriorly, the optic nerve was excised with similar instrumentation. Anterior-to-posterior slits were made in the scleral hemisections to allow for deformation of the curved tissue onto a flat surface. Care was taken not to excise any scleral tissue. A transparent sheet was then placed over the scleral sections, and the borders were traced using a fine tipped marking pen. The tracings were scanned into a Macintosh computer. The scanned images were calibrated and the surface area (cm*) of each was calculated. A second method was used for confirmation of scleral surface area. Eight globes were immersed separately in a graduated cylinder filled with a balanced saline solution to determine volume displacement of the globe (V). Corneas and optic nerves were VOL.
125,
No.
2
HUMAN
SCLERA:
THICKNESS
very thin sclera in profile. A
removed and measured. Even though the eye is not a perfect sphere, the total globe spherical scleral surface area was calculated using the following equations: v = (4/3)ntj By determining the radius (r), surface area was calculated using the following equation: Surface Area = 4nr* The surface area of the cornea and optic nerve was then subtracted from the total globe surface area measurement to determine total scleral surface area.
RESULTS FIGURE 3 INDICATES
THE MEAN
SCLERAL THICKNESS
-+ SD at each l-mm interval from the limbus posteriorly. The mean scleral thickness at the limbal area was 0.53 & 0.14 mm. Near the equator, 13 mm from the limbus, the sclera had a mean thickness of AND
SURFACE
AREA
239
10 mm posterior to the limbus,
the pachymeter measurements were 0.39 & 0.19 mm, and that of the fixed tissue was 0.43 ? 17 mm. The mean scleral surface area calculated from the computerized image tracings was 16.3 -+- 1.8 cm*. Mean surface area measurements using volume displacement by the globes and subtracting the cornea1 and optic nerve surface areas yielded a similar surface area (17.0 -t- 1.5 cm”).
1.3 1.2 1.1 1.0 i
0.3 0.2 0.1 1
DISCUSSION
-.-
b
6
lb
1’5
$0
25
io
35
Distance from Limbus (millimeters)
DURING
FIGURE 3. Line graph comparison of scleral thickness + SD (y-axis) vs the distance (in millimeters; x-axis) from the surgical limbus (left) toward the optic nerve (right).
0.39 ‘-+ 0.17 mm. Three
adjacent regions near the
limbus (I, 2, and 3 mm from the limbus) were compared with three adjacent regions near the equator ( 13, 14, and 15 mm from the limbus) using the unpaired Student t test. Nine combinations were evaluated, and in all cases, the P value of the equatorial area was significantly less than that of the limbal area (P < .025). Five (9%) of the 55 eyes had a scleral thickness of 0.1 mm or less at the equator. Using measurements from 12 to 17 mm posterior to the limbus (approximately the equator), 21 (38%) of the eyes had scleral thickness measurements of 0.25 mm or less. Scleral thickness was observed to increase gradually toward the posterior sclera, achieving a maximal thickness of approximately 0.9 to 1.0 mm near the optic nerve. The slight increase in the mean scleral thickness 5 to 10 mm posterior to the limbus may be explained by the excised rectus muscle insertion. The reproducibility of the measurements from the designated scleral site that was remeasured 10 times was as follows: mean scleral thickness was 10.14 * 0.61 mm, and the coefficient of variation of the mean thickness was 5.9%. Using the ultrasonic measurements, 4 mm posterior to the limbus, the mean of the scleral thickness was 0.47 * 0.13 mm compared with the fixed tissue measurement of 0.51 it 0.12 mm in this region. At 240
AMERICAN
JOURNAL
SCLERAL
BUCKLING
SURGERY, AND NOT UN-
commonly during strabismus surgery, sutures are passed at partial scleral thickness through the sclera near the equator. Interestingly, 21 (38%) of the 55 eyes in this study had scleral thickness measurements of 0.25 mm or less, whereas five (9%) had scleral thickness measurements of 0.1 mm or less in this region. Experienced surgeons look for areas of darkened or “blue sclera” that may indicate thin regions with partially visible choroidal pigmentation. A higher risk of scleral perforation is present in such areas. The results of the present study indicate that these thin areas are quite c:rmmon. Posterior to the equator, scleral thickness increases substantially; however, most surgical procedures utilize the thinner anterior or equatorial regions. Drug delivery to the posterior segment tissues of the eye remains a challenge. The transscleral route of drug delivery is an alternative to direct intraocular injections, systemic delivery, implantable devices, or topical drops. Drug delivery through the sclera is dependent upon the dimensions of surface area and scleral thickness. The sclera is relatively thick near the limbus (0.53 ? 0.14 mm); it thins at the equator (0.39 + 0.17 mm) and becomes substantially thicker near the optic nerve (0.9 to 1.0 mm). Because scleral permeability is inversely proportional to the thickness as determined by surgical thinning of the sclera,2 the ideal location to direct transscleral drug delivery would be near the equator at 12 to 17 mm posterior to the limbus. Additionally, the equatorial area has a large total surface area that is relatively free of adnexal structures. A very thin band of sclera is routinely observed under the insertion of the rectus muscles. This area OF OPHTHALMOLOGY
FEBRUARY
1998
was inconsistently sectioned in the present study and occurred at various distances from the limbus depending upon the orientation of the globe. During extraocular muscle surgery, the surgeon should be cautious when passing sutures posterior to the muscle insertion. This area could represent a site of transscleral drug delivery; however, it has an extremely small overall surface area. Thickness measurements made using ultrasonic pachymetry were used to confirm the measurements made on sectioned globes. The mild discrepancy could be explained by the effect of intraocular pressure, mild hydration of collagen fibers with fixation, or differences in measurement technique and accuracy. Limitations in the measurements of scleral thickness include the following: fresh globes without fixation could not be reproducibly sectioned in a precise manner that would demonstrate a “crisp” edge on projection during thickness measurements, and tissue shrinkage or swelling with fixation could have resulted in variability to the in vivo measurements. Cellular tissue may shrink with fixation, whereas collagenous material may swell.’ The effects of fixation on scleral shrinkage or swelling are unknown. These results may therefore represent a reliable approximation of the relative in vivo scleral thickness. Axial eye length and refractive status of the eye were not correlated with scleral thickness. The mean scleral surface area of 16.3 + 1.8 cm’ is relatively large compared with the cornea1 surface area of approximately 1 cm’.’ The flux of different compounds crossing the sclera is directly proportional to the available surface area. The large surface area of the sclera is an attractive advantage for the transscleral route of intraocular drug delivery. The volumetric method of calculating surface area is less accurate
than the computerized tracing method. Nevertheless, these figures support the mean surface area measurements. It is interesting to note that the scleral surface area of 16.3 + 1.8 cm2 is similar to the total conjunctival surface area (17.65 * 2.12 cm2).6 In summary, we have demonstrated the thickness and total surface area of sclera in a large number of human eyes. These measurements provide anthropometric information that will provide useful data for ophthalmic surgeons and for transscleral difision physiology. Areas of thin sclera are common and may be susceptible to needle or instrument perforation. On the other hand, the thin areas of sclera facilitate permeability and may be advantageous for transscleral drug delivery. More studies are required to determine other physiologic measurements of transscleral drug delivery, such as the effects of intraocular ) pressure and uveal barriers.
REFERENCES 1. Stilling J. 2ur Anatomie des myopischen auges. Z Augenheilkd 1905;14:23-31. 2. Olsen TW, Edelhauser HF, Lim Jl, Geroski DH. Human scleral permeability: effects of age, cryotherapy, transscleral diode laser, and surgical thinning. Invest Ophthalmol Vis Sci 1995;36:1893-1903. 3. Burnette RR. Theory of mass transfer. In: Robinson JR, Lee VH, editors. Theory of mass transfer, 2nd ed. New York: Marcel Dekker, 1987:95-138. 4. Hopwood D. Fixation and hxatives. In: Bancroft JD, Stevens A, editors. Fixation and fixatives, 2nd ed. New York: Churchill Livingstone, 1982:20-40. 5. Watsky MA, Olsen TW, Edelhauser HF. Cornea and sclera. In: Tasman W, Jaeger EA, editors. Cornea and sclera, 1995 edition. Philadelphia: LippincottaRaven, 1995:1-29. 6. Watsky MA, Jablonski MM, Edelhauser HF. Comparison of conjunctival and cornea1 surface areas in rabbit and human. Curr Eye Res 1988;7:483-486.
Authors Interactive@
We encourage questions and comments regarding this article via the Internet on Authors Interactive@ at http://www.ajo.com/ Questions, comments, and author responses are posted.
VOL.
125,
No.
2
HUMAN
SCLERA:
THICKNESS
AND
SURFACE
AREA
241
Sclera: Thickness
and Surface Area
TIMOTHY W. OLSEN, MD, SARAH Y. AABERG, DAYLE H. GEROSKI, PHD, AND HENRY F. EDELHAUSER, PHD PURPOSE: To assess the mean thickness and surface area of human sclera. l METHODS: Fifty-five formalin-fixed eye bank eyes were hemisected from anterior to posterior. Cross-sectional slides were taken to include a millimeter scale ruler in each photograph. Slide photographs were projected and the scleral silhouette sketched. Mean scleral thickness measurements with standard deviation were obtained. Twenty-five human eye bank eyes were used to determine total scleral surface area by either a computerized tracing method ( 17 globes) or vole umetric calculations (eight globes) using fluid displacement. l RESULTS: Mean scleral thickness f SD was 0.53 f 0.14 mm at the corneoscleral limbus, significantly decreasing to 0.39 f 0.17 mm near the equator, and increasing to 0.9 to 1.0 mm near the optic nerve. The mean total scleral surface area by surface area computerized tracings was 16.3 2 1.8 cm2 and, by the volume displacement method, was 17.0 2 1.5 cm*. l CONCLUSIONS: Scleral thickness and surface area measurements from cadaver eyes are important for ophthalmic surgeons and have implications for transscleral diffusion. l
Accepted for publication July 2, 1997. From the Department of Ophthalmology, Emory University, Atlanta, Georgia (Drs Olsen, Geroski, and Edelhauser, and MS Aaberg), and the University of Wisconsin, Madison, and William S. Middleton Memorial Veterans Hospital, Madison, Wisconsin (Dr Olsen). Supported in part by a Fellowship Award (Dr Olsen) from the Heed/Knapp Ophthalmic Foundation, Cleveland, Ohio; core grant P30 EY06360 from the National Eye Institute, Bethesda, Maryland; and an unrestricted grant from Research to Prevent Blindness, Inc, New York, New York (Dr Olsen). Dr Edelhauser is a Research to Prevent Blindness Senior Scholar. Some data from this study are presented as preliminary data in Tasman W, Jaeger EA, editors, Duane’s Foundations of Clinical Ophthalmology, Philadelphia: Lippincott-Raven, 1995. Reprint requests to Timothy W. Olsen, PhD, F4/336 Clinical Science Center, 600 Highland Ave, Madison, WI 53792-3220; fax: (608) 263-1466; e-mail: [email protected]
VOL.
125,
No.
2
0
AMERICAN
JOURNAL
S
CLERAL
DIMENSIONS
ARE
IMPORTANT
BOTH
SURGI-
tally and physiologically. Ophthalmic surgeons frequently perform lamellar dissections of the sclera or pass sutures at various depths within the scleral stroma at different locations on the globe. A precise measurement of scleral thickness and variability of thickness from the corneoscleral limbus to the optic nerve represents critical information for ophthalmic surgeons. Data on scleral thickness measurements are limited and mostly originate from the work of Stilling in 1905.’ Our current emphasis of scleral physiology is focused on transscleral permeability. Permeability is important because fluid and solute flow both out of the globe (that is, uveoscleral outflow) and into the globe (that is, transscleral drug delivery). Two important measurements of human scleral permeability are the total scleral surface area and scleral thickness. We previously demonstrated the relationship of scleral thickness and permeability to compounds varying in molecular weight.’ Additionally, permeability is directly related to flux or the amount of solute crossing a plane of unit surface area, which is normal (perpendicular) to the d’irection of transport per unit of time.3 Determination of transscleral drug delivery necessitates an accurate assessment of regional scleral thickness and total surface area of the human eye. The purpose of this report is to summarize the measurements of scleral thickness and surface area in human eye bank eyes.
METHODS FIFTY-FIVE
EYE
BANK
EYES
WERE
OBTAINED
FROM
THE
Georgia Eye Bank Inc (Atlanta, Georgia), stored in a moist chamber for 3 to 8 days postmortem, then fixed in 10% buffered formalin. Eyes were sectioned from
OF OPHTHALMOLOGY
1998;125:237-241
237
FIGURE 1. Human globe after fixation and transection. The lighting highlights the scleral edge and thick ness. Thi s is a globe with average scleral thickness. A millimeter scale is present inferiorly.
the center of the cornea through the globe in an anterior to posterior direction toward the macular area. The section was directed toward the macular area in order to transect the greater anterior-posterior circle of the eye. The sectioning technique did not consistently incorporate the thin area immediately under the rectus muscle. A high-resolution color slide photograph was taken of the entire globe, perpendicular to the cut edge of the sclera (Figures 1 and 2). A millimeter scale was photographed concomitantly. Photographic slides of sectioned sclera were then projected onto a sheet of paper placed on a solid white tracing screen. Projection distances were adjusted so that 1 mm on the ruler corresponded precisely to 1 cm on the projected image. The scleral silhouette was carefully traced on the paper screen. Perpendicular thickness measurements of the enlarged cut edge were measured using calipers (accurate to 0.05 mm) at every centimeter from the limbus posteriorly toward the optic nerve. These measurements corresponded to measurements taken at l-mm increments on the globe itself. Measurements were converted from centi238
AMERICAN
JOURNAL
meters to millimeters and averaged, and a standard deviation was calculated. To ensure the precision of the scleral measurements, one scleral section was randomly selected, and 10 different measurements of the same site on this section were taken of the posterior sclera near the optic nerve. The projected sclera was traced, and the demarcated region was measured exactly as all other sections. The slide was then removed from the projector, the projector was defocused, and the measurement was repeated 10 times. In another series of experiments, the globe from human donor eyes was inflated to 15 mm Hg by infusing balanced saline solution through the optic nerve. Using a needle through the optic nerve and a ligature, intraocular pressure was maintained at 15 mm Hg and confirmed with pnuemotonometry. Scleral thickness was then measured with an ultrasonic pachymeter. Seventeen fresh eye bank eyes (3 to 8 days postmortem) stored in moist chamber containers we?: used for surface area measurements. Eyes were not OF OPHTHALMOLOGY
FEBRUARY
I 998
FIGURE 2. Human globe after fixation and transection. millimeter scale is present inferiorly.
The cut edge demonstrates
fixed. They were transected at the equator with a razor blade. An anterior-posterior sharp incision was made in the two hemisections, both anteriorly (into the cornea) and posteriorly (into the optic nerve). The corneas were removed at the surgical limbus using a no. 69 blade and corneoscleral scissors. Posteriorly, the optic nerve was excised with similar instrumentation. Anterior-to-posterior slits were made in the scleral hemisections to allow for deformation of the curved tissue onto a flat surface. Care was taken not to excise any scleral tissue. A transparent sheet was then placed over the scleral sections, and the borders were traced using a fine tipped marking pen. The tracings were scanned into a Macintosh computer. The scanned images were calibrated and the surface area (cm*) of each was calculated. A second method was used for confirmation of scleral surface area. Eight globes were immersed separately in a graduated cylinder filled with a balanced saline solution to determine volume displacement of the globe (V). Corneas and optic nerves were VOL.
125,
No.
2
HUMAN
SCLERA:
THICKNESS
very thin sclera in profile. A
removed and measured. Even though the eye is not a perfect sphere, the total globe spherical scleral surface area was calculated using the following equations: v = (4/3)ntj By determining the radius (r), surface area was calculated using the following equation: Surface Area = 4nr* The surface area of the cornea and optic nerve was then subtracted from the total globe surface area measurement to determine total scleral surface area.
RESULTS FIGURE 3 INDICATES
THE MEAN
SCLERAL THICKNESS
-+ SD at each l-mm interval from the limbus posteriorly. The mean scleral thickness at the limbal area was 0.53 & 0.14 mm. Near the equator, 13 mm from the limbus, the sclera had a mean thickness of AND
SURFACE
AREA
239
10 mm posterior to the limbus,
the pachymeter measurements were 0.39 & 0.19 mm, and that of the fixed tissue was 0.43 ? 17 mm. The mean scleral surface area calculated from the computerized image tracings was 16.3 -+- 1.8 cm*. Mean surface area measurements using volume displacement by the globes and subtracting the cornea1 and optic nerve surface areas yielded a similar surface area (17.0 -t- 1.5 cm”).
1.3 1.2 1.1 1.0 i
0.3 0.2 0.1 1
DISCUSSION
-.-
b
6
lb
1’5
$0
25
io
35
Distance from Limbus (millimeters)
DURING
FIGURE 3. Line graph comparison of scleral thickness + SD (y-axis) vs the distance (in millimeters; x-axis) from the surgical limbus (left) toward the optic nerve (right).
0.39 ‘-+ 0.17 mm. Three
adjacent regions near the
limbus (I, 2, and 3 mm from the limbus) were compared with three adjacent regions near the equator ( 13, 14, and 15 mm from the limbus) using the unpaired Student t test. Nine combinations were evaluated, and in all cases, the P value of the equatorial area was significantly less than that of the limbal area (P < .025). Five (9%) of the 55 eyes had a scleral thickness of 0.1 mm or less at the equator. Using measurements from 12 to 17 mm posterior to the limbus (approximately the equator), 21 (38%) of the eyes had scleral thickness measurements of 0.25 mm or less. Scleral thickness was observed to increase gradually toward the posterior sclera, achieving a maximal thickness of approximately 0.9 to 1.0 mm near the optic nerve. The slight increase in the mean scleral thickness 5 to 10 mm posterior to the limbus may be explained by the excised rectus muscle insertion. The reproducibility of the measurements from the designated scleral site that was remeasured 10 times was as follows: mean scleral thickness was 10.14 * 0.61 mm, and the coefficient of variation of the mean thickness was 5.9%. Using the ultrasonic measurements, 4 mm posterior to the limbus, the mean of the scleral thickness was 0.47 * 0.13 mm compared with the fixed tissue measurement of 0.51 it 0.12 mm in this region. At 240
AMERICAN
JOURNAL
SCLERAL
BUCKLING
SURGERY, AND NOT UN-
commonly during strabismus surgery, sutures are passed at partial scleral thickness through the sclera near the equator. Interestingly, 21 (38%) of the 55 eyes in this study had scleral thickness measurements of 0.25 mm or less, whereas five (9%) had scleral thickness measurements of 0.1 mm or less in this region. Experienced surgeons look for areas of darkened or “blue sclera” that may indicate thin regions with partially visible choroidal pigmentation. A higher risk of scleral perforation is present in such areas. The results of the present study indicate that these thin areas are quite c:rmmon. Posterior to the equator, scleral thickness increases substantially; however, most surgical procedures utilize the thinner anterior or equatorial regions. Drug delivery to the posterior segment tissues of the eye remains a challenge. The transscleral route of drug delivery is an alternative to direct intraocular injections, systemic delivery, implantable devices, or topical drops. Drug delivery through the sclera is dependent upon the dimensions of surface area and scleral thickness. The sclera is relatively thick near the limbus (0.53 ? 0.14 mm); it thins at the equator (0.39 + 0.17 mm) and becomes substantially thicker near the optic nerve (0.9 to 1.0 mm). Because scleral permeability is inversely proportional to the thickness as determined by surgical thinning of the sclera,2 the ideal location to direct transscleral drug delivery would be near the equator at 12 to 17 mm posterior to the limbus. Additionally, the equatorial area has a large total surface area that is relatively free of adnexal structures. A very thin band of sclera is routinely observed under the insertion of the rectus muscles. This area OF OPHTHALMOLOGY
FEBRUARY
1998
was inconsistently sectioned in the present study and occurred at various distances from the limbus depending upon the orientation of the globe. During extraocular muscle surgery, the surgeon should be cautious when passing sutures posterior to the muscle insertion. This area could represent a site of transscleral drug delivery; however, it has an extremely small overall surface area. Thickness measurements made using ultrasonic pachymetry were used to confirm the measurements made on sectioned globes. The mild discrepancy could be explained by the effect of intraocular pressure, mild hydration of collagen fibers with fixation, or differences in measurement technique and accuracy. Limitations in the measurements of scleral thickness include the following: fresh globes without fixation could not be reproducibly sectioned in a precise manner that would demonstrate a “crisp” edge on projection during thickness measurements, and tissue shrinkage or swelling with fixation could have resulted in variability to the in vivo measurements. Cellular tissue may shrink with fixation, whereas collagenous material may swell.’ The effects of fixation on scleral shrinkage or swelling are unknown. These results may therefore represent a reliable approximation of the relative in vivo scleral thickness. Axial eye length and refractive status of the eye were not correlated with scleral thickness. The mean scleral surface area of 16.3 + 1.8 cm’ is relatively large compared with the cornea1 surface area of approximately 1 cm’.’ The flux of different compounds crossing the sclera is directly proportional to the available surface area. The large surface area of the sclera is an attractive advantage for the transscleral route of intraocular drug delivery. The volumetric method of calculating surface area is less accurate
than the computerized tracing method. Nevertheless, these figures support the mean surface area measurements. It is interesting to note that the scleral surface area of 16.3 + 1.8 cm2 is similar to the total conjunctival surface area (17.65 * 2.12 cm2).6 In summary, we have demonstrated the thickness and total surface area of sclera in a large number of human eyes. These measurements provide anthropometric information that will provide useful data for ophthalmic surgeons and for transscleral difision physiology. Areas of thin sclera are common and may be susceptible to needle or instrument perforation. On the other hand, the thin areas of sclera facilitate permeability and may be advantageous for transscleral drug delivery. More studies are required to determine other physiologic measurements of transscleral drug delivery, such as the effects of intraocular ) pressure and uveal barriers.
REFERENCES 1. Stilling J. 2ur Anatomie des myopischen auges. Z Augenheilkd 1905;14:23-31. 2. Olsen TW, Edelhauser HF, Lim Jl, Geroski DH. Human scleral permeability: effects of age, cryotherapy, transscleral diode laser, and surgical thinning. Invest Ophthalmol Vis Sci 1995;36:1893-1903. 3. Burnette RR. Theory of mass transfer. In: Robinson JR, Lee VH, editors. Theory of mass transfer, 2nd ed. New York: Marcel Dekker, 1987:95-138. 4. Hopwood D. Fixation and hxatives. In: Bancroft JD, Stevens A, editors. Fixation and fixatives, 2nd ed. New York: Churchill Livingstone, 1982:20-40. 5. Watsky MA, Olsen TW, Edelhauser HF. Cornea and sclera. In: Tasman W, Jaeger EA, editors. Cornea and sclera, 1995 edition. Philadelphia: LippincottaRaven, 1995:1-29. 6. Watsky MA, Jablonski MM, Edelhauser HF. Comparison of conjunctival and cornea1 surface areas in rabbit and human. Curr Eye Res 1988;7:483-486.
Authors Interactive@
We encourage questions and comments regarding this article via the Internet on Authors Interactive@ at http://www.ajo.com/ Questions, comments, and author responses are posted.
VOL.
125,
No.
2
HUMAN
SCLERA:
THICKNESS
AND
SURFACE
AREA
241