- Email: [email protected]
High-frequency ultrasound of anterior segment retinoblastoma
reduction potential and acidic milieu. Suspicion of C septicum panophthalmitis demands aggressive treatment with intravenous antibiotics coupled with removal or debridement of infected tissue, as delay can lead rapidly to death. Prompt recognition is important to improve the prognosis of this devastating disease and a thorough systemic evaluation is necessary to determine the portal of entry. REFERENCES
1. Matter MA, Cortinas TI, de Guzman AM. Effects of temperature and glucose concentration on DNase production by Clostridium septicum. Clin Infect Dis 1997;25(Suppl 2): S158 –159. 2. Larson CM, Bubrick MP, Jacobs DM, West MA. Malignancy, mortality, and medicosurgical management of Clostridium septicum. Surgery 1995;118:592–598. 3. Insler MS, Karcioglu ZA, Naugle T Jr. Clostridium septicum panopthalmitis with systemic complications. Br J Ophthalmol 1985;69:774 –777. 4. Green MT, Font RL, Campbell JV, Marines HM. Endogenous clostridium panopthalmitis. Ophthalmology 1987;94:435– 438. 5. Cannistra AJ, Albert DM, Frambach DA, Dreher RJ, Roberts L. Sudden visual loss associated with clostridial bacteraemia. Br J Ophthalmol 1988;72:380 –385.
High-frequency Ultrasound of Anterior Segment Retinoblastoma Paul T. Finger, MD, Seth W. Meskin, MD, H. Jay Wisnicki, MD, Zurab Albekioni, MD, and Susan Schneider, MD To evaluate anterior segment retinoblastoma with high-frequency ultrasound. DESIGN: Interventional case report. METHODS: An 11-year-old boy with a total retinal detachment and multiple white anterior chamber nodules was examined with high-frequency ultrasound before enucleation of the globe. RESULTS: Multiple solid and cystic nodular tumors were found in the anterior chamber angle. With high-frequency ultrasound, tumor was discovered posterior to the iris, over the ciliary processes, and on the lens capsule. No calcifications were noted. Other findings included angle closure related to iris neovascularization and uveal thickening. CONCLUSION: High-frequency ultrasound can be used to evaluate retinoblastoma extension into the anterior segment. These images may be used for comparison in future
FIGURE 1. (Top) A slit-lamp photograph shows multiple white nodular tumors in the inferior anterior chamber angle (with a cystic appearing tumor on top). Additional tumors are noted in the 2 o’clock and 8 o’clock meridians. Iris neovascularization is present. (Bottom) Histopathologic section corresponding to the meridian of the ultrasound section seen in Figure 2, bottom left and right. Note the blue tumor does not extend within the ciliary body, but is noted to cover the pars plana, ciliary processes, and lens capsule. The ciliary body is thickened by inflammation (hematoxylin and eosin ⴛ 40).
PURPOSE:
cases of retinoblastoma with anterior chamber invasion. (Am J Ophthalmol 2004;137:944 –946. © 2004 by Elsevier Inc. All rights reserved.)
R
rior chamber. When it occurs, white nodular tumors can be fixed in the anterior chamber angle or seen to move with gravity falling to rest on the dependent meridian of the iris. Anterior chamber retinoblastoma has been associated with a poor ocular prognosis (Figure 1, top panel).1 This diagnosis is typically made on a clinical basis (without a biopsy), and enucleation establishes the diagnosis (Figure 1, bottom panel). We describe a case evaluated by clinical examination and high-frequency ultrasonography.
Accepted for publication Oct 17, 2003. From The New York Eye Cancer Center, The New York Eye and Ear Infirmary, New York, New York. Inquiries to Paul T. Finger, MD, The New York Eye Cancer Center, 115 East 61st Street, New York, NY 10021; Tel: (212) 832-8170; e-mail: [email protected]
944
AMERICAN JOURNAL
ETINOBLASTOMA RARELY EXTENDS INTO THE ANTE-
OF
OPHTHALMOLOGY
MAY 2004
FIGURE 2. (Top Left) High-frequency ultrasound reveals a large cystic retinoblastoma seed (note the central lucency). (Top Right) Another solid and ovoid tumor nodule. Both nodules appear to be resting on the iris stroma. (Bottom Left) This ultrasonogram reveals multiple anterior chamber echo-densities (arrows) and tumor extending so as to cover the ciliary processes and peripheral anterior lens capsule. (Bottom Right) Note tumor deposits on the pars plana. Moderately reflective tumor is noted at the iris root extending into the anterior chamber.
An 11-year-old boy had presented with a long-standing total retinal detachment in the right eye without history of trauma. He was referred to the Ocular Tumor Service of The New York Eye and Ear Infirmary due to the presence of multiple white anterior segment tumors (Figure 1, top panel). On examination, his visual acuity was no light perception in the right eye and 20/25 in the left eye. Both a right afferent pupillary defect and right exotropia were noted. Slit-lamp examination revealed multiple white nodular tumors, iris neovascularization, trace hyphema, and a slightly edematous cornea (Figure 1, top panel). Most of the tumors were noted to be free-floating, deposited in the inferior angle due to gravity. His intraocular pressure was 25 mm Hg in the right eye, and indirect ophthalmoscopy of the right eye revealed no view. Examination of the left eye was normal. VOL. 137, NO. 5
Our clinical diagnosis of retinoblastoma was supported by a computed tomogram that revealed a calcification within the tumor.2,3 The eye was evaluated with lowfrequency ultrasound of the posterior segment as well as high-frequency ultrasound of the anterior segment and tumor seeds (Figure 2). Low-frequency ultrasound revealed a total closed funnel retinal detachment and diffuse retinal thickening.4 Highfrequency ultrasound revealed both solid and cystic tumors. Iris neovascularization was associated with anterior synechiae and angle closure.2,3 Tumor could be visualized on the lens surface and ciliary body.3 The uvea appeared thickened (Figure 2). Lastly, multiple small echoes could be seen within the aqueous humor. No calcifications were noted on ultrasound. The eye was enucleated and the diagnosis of retinoblastoma confirmed (Figure 1, bottom panel). Histopa-
BRIEF REPORTS
945
thology confirmed the presence of retinoblastoma on the pars plana, pars plicata, lens surface and in the anterior chamber. Though a metastatic survey was negative, the delay in diagnosis was considered a risk factor for metastasis, and the patient received adjuvant chemotherapy for presumed micrometastasis.5 There appear to be no published cases of highfrequency ultrasound of anterior segment involvement by retinoblastoma seeds. In addition, high-frequency ultrasound was used to uncover tumors clinically hidden behind the iris, over the ciliary processes, and on lens capsule. Therefore, in this atypical case in an 11-yearold boy with a T2b N0 M0 retinoblastoma, the anterior segment findings of white nodular tumors, high-frequency ultrasound images of tumor behind the iris, and the single focus of calcification on computed tomography led us to the clinical diagnosis of retinoblastoma.6 Like most retinoblastomas with anterior segment extension, this eye was enucleated.
To evaluate the retina in autopsy eyes from patients over age 60 with autosomal dominant retinitis pigmentosa and a mutation in the RP13 gene (designated as PRPC8, Arg2310Gly), rhodopsin Pro23His, rhodopsin Cys110Arg, or rhodopsin Glu181Lys. DESIGN: Histologic study of the retina. METHODS: All eyes were prepared for electron microscopy within 12 hours after death. RESULTS: All eyes showed loss of rod photoreceptors. Remaining cones showed perinuclear membranous swirls, inclusion bodies in the inner segments, and shortened or absent outer segments despite causation by various gene defects. CONCLUSION: The comparable histologic findings in these four cases suggest a final common pathway leading to photoreceptor cell death in these dominant forms of retinitis pigmentosa. (Am J Ophthalmol 2004;137:946 –948. © 2004 by Elsevier Inc. All rights reserved.) PURPOSE:
REFERENCES
1. Haik BG, Dunleavy SA, Cooke C, et al. Retinoblastoma with anterior chamber extension. Ophthalmology 1987;94:367– 370. 2. Amemiya T, Yoshida H, Ishigooka H. Vitreous seeds in retinoblastoma, clinical significance and ultrastructure. Graefes Arch Klin Exp Ophthalmol 1979;211:205–213. 3. Garner A, Kanski JJ, Kinnear F. Retinoblastoma: Report of a case with minimal retinal involvement but massive anterior segment spread. Br J Ophthalmol 1987;71:858 – 863. 4. Finger PT, Khoobehi A, Ponce-Contreras MR, Della Rocca D, Garcia JP Jr. Three-dimensional ultrasound of retinoblastoma: Initial experience. Br J Ophthalmol 2002;86: 1136 –1138. 5. Finger PT, Harbour JW, Karcioglu Z. Risk factors for metastasis in retinoblastoma. Surv Ophthalmol 2002;47:1–16. 6. Finger PT. Guest editorial: Do you speak ocular tumor? Ophthalmology 2003;110:13–14.
I
eyes of a 63-year-old woman with autosomal dominant retinitis pigmentosa (ADRP).1 The donor’s daughter was recently found to have the missense mutation Arg2310Gly in the PRPC8 gene (that is, encoding the pre-mRNA processing factor 8 that is the homologue of yeast Prp8). In light of this new gene identification, we reevaluated the donor’s histologic findings and compared them with two other cases of ADRP caused by rhodopsin Glu181Lys and rhodopsin Pro23His mutations,2,3 as well as a third case with rhodopsin Cys110Arg. All eyes were fixed in a phosphate buffer containing 2.5% glutaraldehyde and 1% formaldehyde. Thin sections were cut on an ultramicrotome, appropriately stained, and viewed on an electron microscope. The patient whose daughter has the PRPC8 mutation had no rod photoreceptors and a reduced number of cone photoreceptors with shortened or absent outer segments. The cones contained perinuclear membranous swirls (solid arrow in Figure 1A) and inclusion bodies (open arrow in Figure 1A) in the inner segments. The retinal pigment epithelium and choroid were intact. The eyes from the three patients with rhodopsin mutations, aged 76, 77, and 84, also had no rod photoreceptors; remaining cones had shortened or absent outer segments (Figure 1, B, C, and D). The inner segments abutted the retinal pigment epithelium (for example, see Figure 1C). The cone photoreceptors in the patients with rhodopsin Glu181Lys and Cys110Arg (see Figure 1, B and D) also had inclusion bodies in the inner segments. The eye with the Glu181Lys mutation had perinuclear membranous swirls (solid arrow, Figure 1B ). The patients with the Pro23His and Glu181Lys mutations showed only patches of retinal pig-
Histologic Study of Retinitis Pigmentosa Due to a Mutation in the RP13 Gene (PRPC8): Comparison With Rhodopsin Pro23His, Cys110Arg, and Glu181Lys King To, MD, Michael Adamian, BS, and Eliot L. Berson, MD
Accepted for publication Oct 30, 2003. From the Berman-Gund Laboratory for the Study of Retinal Degenerations, Harvard Medical School, Massachusetts Eye and Ear Infirmary, Boston, Massachusetts. Supported by a Center Grant from the Foundation Fighting Blindness, Owings Mills, Maryland. Inquiries to Eliot L. Berson, MD, Berman-Gund Laboratory, 243 Charles Street, Boston, MA 02114; fax: (617) 573–3216.
946
AMERICAN JOURNAL
N 1977, WE DESCRIBED HISTOLOGIC FINDINGS IN AUTOPSY
OF
OPHTHALMOLOGY
MAY 2004
1. Matter MA, Cortinas TI, de Guzman AM. Effects of temperature and glucose concentration on DNase production by Clostridium septicum. Clin Infect Dis 1997;25(Suppl 2): S158 –159. 2. Larson CM, Bubrick MP, Jacobs DM, West MA. Malignancy, mortality, and medicosurgical management of Clostridium septicum. Surgery 1995;118:592–598. 3. Insler MS, Karcioglu ZA, Naugle T Jr. Clostridium septicum panopthalmitis with systemic complications. Br J Ophthalmol 1985;69:774 –777. 4. Green MT, Font RL, Campbell JV, Marines HM. Endogenous clostridium panopthalmitis. Ophthalmology 1987;94:435– 438. 5. Cannistra AJ, Albert DM, Frambach DA, Dreher RJ, Roberts L. Sudden visual loss associated with clostridial bacteraemia. Br J Ophthalmol 1988;72:380 –385.
High-frequency Ultrasound of Anterior Segment Retinoblastoma Paul T. Finger, MD, Seth W. Meskin, MD, H. Jay Wisnicki, MD, Zurab Albekioni, MD, and Susan Schneider, MD To evaluate anterior segment retinoblastoma with high-frequency ultrasound. DESIGN: Interventional case report. METHODS: An 11-year-old boy with a total retinal detachment and multiple white anterior chamber nodules was examined with high-frequency ultrasound before enucleation of the globe. RESULTS: Multiple solid and cystic nodular tumors were found in the anterior chamber angle. With high-frequency ultrasound, tumor was discovered posterior to the iris, over the ciliary processes, and on the lens capsule. No calcifications were noted. Other findings included angle closure related to iris neovascularization and uveal thickening. CONCLUSION: High-frequency ultrasound can be used to evaluate retinoblastoma extension into the anterior segment. These images may be used for comparison in future
FIGURE 1. (Top) A slit-lamp photograph shows multiple white nodular tumors in the inferior anterior chamber angle (with a cystic appearing tumor on top). Additional tumors are noted in the 2 o’clock and 8 o’clock meridians. Iris neovascularization is present. (Bottom) Histopathologic section corresponding to the meridian of the ultrasound section seen in Figure 2, bottom left and right. Note the blue tumor does not extend within the ciliary body, but is noted to cover the pars plana, ciliary processes, and lens capsule. The ciliary body is thickened by inflammation (hematoxylin and eosin ⴛ 40).
PURPOSE:
cases of retinoblastoma with anterior chamber invasion. (Am J Ophthalmol 2004;137:944 –946. © 2004 by Elsevier Inc. All rights reserved.)
R
rior chamber. When it occurs, white nodular tumors can be fixed in the anterior chamber angle or seen to move with gravity falling to rest on the dependent meridian of the iris. Anterior chamber retinoblastoma has been associated with a poor ocular prognosis (Figure 1, top panel).1 This diagnosis is typically made on a clinical basis (without a biopsy), and enucleation establishes the diagnosis (Figure 1, bottom panel). We describe a case evaluated by clinical examination and high-frequency ultrasonography.
Accepted for publication Oct 17, 2003. From The New York Eye Cancer Center, The New York Eye and Ear Infirmary, New York, New York. Inquiries to Paul T. Finger, MD, The New York Eye Cancer Center, 115 East 61st Street, New York, NY 10021; Tel: (212) 832-8170; e-mail: [email protected]
944
AMERICAN JOURNAL
ETINOBLASTOMA RARELY EXTENDS INTO THE ANTE-
OF
OPHTHALMOLOGY
MAY 2004
FIGURE 2. (Top Left) High-frequency ultrasound reveals a large cystic retinoblastoma seed (note the central lucency). (Top Right) Another solid and ovoid tumor nodule. Both nodules appear to be resting on the iris stroma. (Bottom Left) This ultrasonogram reveals multiple anterior chamber echo-densities (arrows) and tumor extending so as to cover the ciliary processes and peripheral anterior lens capsule. (Bottom Right) Note tumor deposits on the pars plana. Moderately reflective tumor is noted at the iris root extending into the anterior chamber.
An 11-year-old boy had presented with a long-standing total retinal detachment in the right eye without history of trauma. He was referred to the Ocular Tumor Service of The New York Eye and Ear Infirmary due to the presence of multiple white anterior segment tumors (Figure 1, top panel). On examination, his visual acuity was no light perception in the right eye and 20/25 in the left eye. Both a right afferent pupillary defect and right exotropia were noted. Slit-lamp examination revealed multiple white nodular tumors, iris neovascularization, trace hyphema, and a slightly edematous cornea (Figure 1, top panel). Most of the tumors were noted to be free-floating, deposited in the inferior angle due to gravity. His intraocular pressure was 25 mm Hg in the right eye, and indirect ophthalmoscopy of the right eye revealed no view. Examination of the left eye was normal. VOL. 137, NO. 5
Our clinical diagnosis of retinoblastoma was supported by a computed tomogram that revealed a calcification within the tumor.2,3 The eye was evaluated with lowfrequency ultrasound of the posterior segment as well as high-frequency ultrasound of the anterior segment and tumor seeds (Figure 2). Low-frequency ultrasound revealed a total closed funnel retinal detachment and diffuse retinal thickening.4 Highfrequency ultrasound revealed both solid and cystic tumors. Iris neovascularization was associated with anterior synechiae and angle closure.2,3 Tumor could be visualized on the lens surface and ciliary body.3 The uvea appeared thickened (Figure 2). Lastly, multiple small echoes could be seen within the aqueous humor. No calcifications were noted on ultrasound. The eye was enucleated and the diagnosis of retinoblastoma confirmed (Figure 1, bottom panel). Histopa-
BRIEF REPORTS
945
thology confirmed the presence of retinoblastoma on the pars plana, pars plicata, lens surface and in the anterior chamber. Though a metastatic survey was negative, the delay in diagnosis was considered a risk factor for metastasis, and the patient received adjuvant chemotherapy for presumed micrometastasis.5 There appear to be no published cases of highfrequency ultrasound of anterior segment involvement by retinoblastoma seeds. In addition, high-frequency ultrasound was used to uncover tumors clinically hidden behind the iris, over the ciliary processes, and on lens capsule. Therefore, in this atypical case in an 11-yearold boy with a T2b N0 M0 retinoblastoma, the anterior segment findings of white nodular tumors, high-frequency ultrasound images of tumor behind the iris, and the single focus of calcification on computed tomography led us to the clinical diagnosis of retinoblastoma.6 Like most retinoblastomas with anterior segment extension, this eye was enucleated.
To evaluate the retina in autopsy eyes from patients over age 60 with autosomal dominant retinitis pigmentosa and a mutation in the RP13 gene (designated as PRPC8, Arg2310Gly), rhodopsin Pro23His, rhodopsin Cys110Arg, or rhodopsin Glu181Lys. DESIGN: Histologic study of the retina. METHODS: All eyes were prepared for electron microscopy within 12 hours after death. RESULTS: All eyes showed loss of rod photoreceptors. Remaining cones showed perinuclear membranous swirls, inclusion bodies in the inner segments, and shortened or absent outer segments despite causation by various gene defects. CONCLUSION: The comparable histologic findings in these four cases suggest a final common pathway leading to photoreceptor cell death in these dominant forms of retinitis pigmentosa. (Am J Ophthalmol 2004;137:946 –948. © 2004 by Elsevier Inc. All rights reserved.) PURPOSE:
REFERENCES
1. Haik BG, Dunleavy SA, Cooke C, et al. Retinoblastoma with anterior chamber extension. Ophthalmology 1987;94:367– 370. 2. Amemiya T, Yoshida H, Ishigooka H. Vitreous seeds in retinoblastoma, clinical significance and ultrastructure. Graefes Arch Klin Exp Ophthalmol 1979;211:205–213. 3. Garner A, Kanski JJ, Kinnear F. Retinoblastoma: Report of a case with minimal retinal involvement but massive anterior segment spread. Br J Ophthalmol 1987;71:858 – 863. 4. Finger PT, Khoobehi A, Ponce-Contreras MR, Della Rocca D, Garcia JP Jr. Three-dimensional ultrasound of retinoblastoma: Initial experience. Br J Ophthalmol 2002;86: 1136 –1138. 5. Finger PT, Harbour JW, Karcioglu Z. Risk factors for metastasis in retinoblastoma. Surv Ophthalmol 2002;47:1–16. 6. Finger PT. Guest editorial: Do you speak ocular tumor? Ophthalmology 2003;110:13–14.
I
eyes of a 63-year-old woman with autosomal dominant retinitis pigmentosa (ADRP).1 The donor’s daughter was recently found to have the missense mutation Arg2310Gly in the PRPC8 gene (that is, encoding the pre-mRNA processing factor 8 that is the homologue of yeast Prp8). In light of this new gene identification, we reevaluated the donor’s histologic findings and compared them with two other cases of ADRP caused by rhodopsin Glu181Lys and rhodopsin Pro23His mutations,2,3 as well as a third case with rhodopsin Cys110Arg. All eyes were fixed in a phosphate buffer containing 2.5% glutaraldehyde and 1% formaldehyde. Thin sections were cut on an ultramicrotome, appropriately stained, and viewed on an electron microscope. The patient whose daughter has the PRPC8 mutation had no rod photoreceptors and a reduced number of cone photoreceptors with shortened or absent outer segments. The cones contained perinuclear membranous swirls (solid arrow in Figure 1A) and inclusion bodies (open arrow in Figure 1A) in the inner segments. The retinal pigment epithelium and choroid were intact. The eyes from the three patients with rhodopsin mutations, aged 76, 77, and 84, also had no rod photoreceptors; remaining cones had shortened or absent outer segments (Figure 1, B, C, and D). The inner segments abutted the retinal pigment epithelium (for example, see Figure 1C). The cone photoreceptors in the patients with rhodopsin Glu181Lys and Cys110Arg (see Figure 1, B and D) also had inclusion bodies in the inner segments. The eye with the Glu181Lys mutation had perinuclear membranous swirls (solid arrow, Figure 1B ). The patients with the Pro23His and Glu181Lys mutations showed only patches of retinal pig-
Histologic Study of Retinitis Pigmentosa Due to a Mutation in the RP13 Gene (PRPC8): Comparison With Rhodopsin Pro23His, Cys110Arg, and Glu181Lys King To, MD, Michael Adamian, BS, and Eliot L. Berson, MD
Accepted for publication Oct 30, 2003. From the Berman-Gund Laboratory for the Study of Retinal Degenerations, Harvard Medical School, Massachusetts Eye and Ear Infirmary, Boston, Massachusetts. Supported by a Center Grant from the Foundation Fighting Blindness, Owings Mills, Maryland. Inquiries to Eliot L. Berson, MD, Berman-Gund Laboratory, 243 Charles Street, Boston, MA 02114; fax: (617) 573–3216.
946
AMERICAN JOURNAL
N 1977, WE DESCRIBED HISTOLOGIC FINDINGS IN AUTOPSY
OF
OPHTHALMOLOGY
MAY 2004