A
B
Figure 2. Postoperative fundus photograph and fluorescein angiography of the right eye. A, The patient is fixating on the camera’s fixation marker. The superiorly translocated retina is overlying healthier retinal pigment epithelium (RPE), and the previously noted area of RPE atrophy is seen inferiorly (arrowheads). The inferior edge of the lesion is highlighted (arrow). B, A middle angiographic frame confirms that the translocated retina is overlying healthier RPE.
macular edema, macular pucker, diplopia, and cyclotropia.4,5 Full visual rehabilitation after MT360 also requires silicone oil removal and strabismus surgery.4,5 Because of photoreceptor and retinal pigment epithelial degeneration, retinal translocation would not be expected to improve visual function in long-standing cases of GA.7 In contrast, 50% of eyes with early GA and good vision have reduced contrast sensitivity and reading rates secondary to parafoveal scotomata.7 Eyes with GA and recent visual loss, or reduced visual function with good central vision, may benefit from MT360 before severe foveal photoreceptor degeneration occurs. However, the potential for visual recovery must be weighed against the sight-threatening complications associated with this surgery. A case-control study may be warranted to investigate the treatment of these selected cases of endstage nonneovascular AMD with MT360. Mark T. Cahill, FRCOphth Sharon F. Freedman, MD Cynthia A. Toth, MD Durham, NC We thank John T. Harriott, MD, Winston-Salem, NC, for his referral of the patient, his thoughtful input, and his assistance with the care of the patient.
Corresponding author: Cynthia A. Toth, MD, Duke University Eye Center, Room 107, Erwin Road, PO Box 3802, Durham, NC 27710 (e-mail:
[email protected]). 1. Klein R, Wang Q, Klein BEK, Moss SE, Meuer SM. The relationship of age-related maculopathy, cataract and glaucoma to visual acuity. Invest Ophthalmol Vis Sci. 1995;36:182-191. 2. Wang JJ, Mitchell P, Smith W, Cumming RG. Bilateral involvement by age related maculopathy lesions in a population. Br J Ophthalmol. 1998; 82:743-747. 3. Machemer R, Steinhorst UH. Retinal separation, retinotomy, and macular relocation, II: a surgical approach for age-related macular degeneration? Graefes Arch Clin Exp Ophthalmol. 1993;231:635-641. 4. Eckardt C, Eckardt U, Conraf HG. Macular rotation with and without counter-rotation of the globe in patients with age-related macular degeneration. Graefes Arch Clin Exp Ophthalmol. 1999;237:313-325. 5. Toth CA, Freedman SF. Macular translocation with 360-degree peripheral retinectomy impact of technique and surgical experience on visual outcomes. Retina. 2001;21:293-303. 6. Benner JD, Sunness JS, Ziegler MD, Soltanian J. Limited macular translocation for atrophic maculopathy. Arch Ophthalmol. 2002;120:586-591. 7. Sunness JS, Rubin GS, Applegate CA, et al. Visual function abnormalities and prognosis in eyes with age-related geographic atrophy of the macula and good visual acuity. Ophthalmology. 1997;104:1677-1691.
Presumed TeratomaAssociated Paraneoplastic Retinopathy
Paraneoplastic retinopathies are characterized by retinal dysfunction owing to the remote effects of systemic
(REPRINTED) ARCH OPHTHALMOL / VOL 121, JAN 2003 133
malignancy.1 The mechanism of retinal degeneration in these syndromes is believed to be related to the presence of autoantibodies against tumor-related antigens that crossreact with molecularly similar retinal antigens. The two most frequently described paraneoplastic retinopathies are cancer-associated retinopathy and melanoma-associated retinopathy (MAR), each of which has well-described clinical and electrophysiologic features. Cancerassociated retinopathy is most commonly associated with small-cell lung carcinoma but has also been associated with breast, cervical, and uterine cancer. Recoverin, one of the antigens implicated in cancer-associated retinopathy, has been detected in a patient with autoimmune retinopathy in the absence of demonstrable malignancy.2 We report a case of presumed paraneoplastic retinopathy associated clinicopathologically with a mature teratoma. Report of a Case. A 39-year-old Gambian woman was referred for evaluation of bilateral vitritis. Three months before her initial visit, she noted the sudden onset of blurred vision, nyctalopia, shimmering photopsias, and a migrainous head ache. Her ocular symptoms gradually worsened during the following 3 months, despite resolution of head-
WWW.ARCHOPHTHALMOL.COM
©2003 American Medical Association. All rights reserved. Downloaded From: http://archopht.jamanetwork.com/ by a National Institutes of Health User on 08/02/2013
A
C
B
Figure 1. Photographs illustrate optic nerve cupping and retinovascular attenuation in the right eye (A) and left eye (B). C, The demarcation line is between normal-appearing retinal pigment epithelium in the posterior pole of the right eye and hypopigmented retinal pigment epithelium in the periphery.
A
B
Figure 2. Full-threshold Humphrey 30-2 visual fields, stimulus size V in the right (A) and left (B) eyes, demonstrate profoundly constricted visual fields recorded at the initial visit. There were no fixation losses or false-positive errors in either study (false-negative errors, 5/19 in the right eye and 4/11 in the left eye).
ache symptoms. Her medical history was remarkable only for childhood malaria treated with quinine. Her ophthalmic history was unremarkable. Ophthalmic evaluation documented visual acuity of 20/16 OD and 20/25 OS with intraocular pressures of 15 mm Hg OD and 13 mm Hg OS. Results of anterior segment biomicroscopy were normal in both eyes. Funduscopic examination revealed 1+ vitreous cells in the right eye and 2+ vitreous cells in the left eye, with no vitreous haze in either eye. The optic nerve cup-disc ratio was 0.9 OU without pallor or edema (Figure 1A and B). The maculae were normal. Mild arteriolar attenuation and peripheral vascular sheathing were present in both eyes. Distinct areas of peripheral retinal pigment epithelial depigmentation were present bi-
laterally (Figure 1C). Results of a comprehensive laboratory evaluation, including serum chemistry, liver functions, complete blood cell count, syphilis serologic testing, and angiotensin-converting enzyme levels, were unremarkable. Humphrey visual fields were profoundly constricted bilaterally (Figure 2). In electroretinograms (ERGs) recorded according to the international standard technique,3 combined (rod-and-cone–mediated) maximal responses had an “electronegative” configuration (Figure 3A). Cone-mediated ERGs elicited by 100millisecond stimuli showed absence of the “on” response with relative preservation of the “off” response (Figure 3B). The characteristic ERG and clinical history raised the possibility of MAR. Results of comprehen-
(REPRINTED) ARCH OPHTHALMOL / VOL 121, JAN 2003 134
sive dermatologic and systemic metastatic evaluations were negative, except for a computed tomographic scan of the chest, which revealed a cystic anterior mediastinal mass consistent with teratoma (Figure 4). Two fine-needle aspirations of the mass were performed and were nondiagnostic. Serum analyses for ␣-fetoprotein and –human chorionic gonadotropin, tumor markers for teratoma, were negative. During the following 6 months, the patient received 3 periocular injections of 40 mg of triamcinolone acetonide (Kenalog; Bristol-Myers Squibb, New York, NY) in both eyes. There was a subsequent decrease in the vitreous cell count and documented improvement in the visual fields bilaterally (Figure 5). During this time, serial computed tomographic scans demonstrated progressive growth of the mediastinal lesion, threatening the great vessels of the chest. Median sternotomy and excisional resection of the tumor was subsequently performed. Gross inspection of the tumor revealed a multicystic mass with hair projecting into the central cavity. Histopathologic analysis confirmed the diagnosis of a mature teratoma (Figure 6A). Staining of the tumor with HMB45, an immunoreagant specific for melanocytic elements, was negative (Figure 6B). In contrast, immunostaining with antibodies against retinal S antigen produced avid staining of multiple tis-
WWW.ARCHOPHTHALMOL.COM
©2003 American Medical Association. All rights reserved. Downloaded From: http://archopht.jamanetwork.com/ by a National Institutes of Health User on 08/02/2013
B
A
OS
Amplitude, 100 µV/Division
Amplitude, 200 µV/Division
OD OD
OS
Control
0
50
100
150
200
Control
0
50
100
150
200
Time, ms
Time, ms
Figure 3. Patient electroretinograms (ERGs) and ERGs from representative healthy controls. A, An ERG elicited by brief (10-millisecond), bright (1.64-candela/m2) full-field flashes after dark adaptation. The vertical line denotes flash onset. Note that the b-wave amplitude (OD, 131 µV; OS, 42 µV; lower limit of normal, 373 µV) is considerably more reduced than the a-wave amplitude (OD, 253 µV; OS, 107 µV; lower limit of normal, 188 µV). B, An ERG elicited by prolonged (100-millisecond), bright (1.64-candela/m2) full-field flashes after light adaptation. The vertical lines denote flash onset (0 milliseconds) and offset (100 milliseconds). Note that the amplitude of “on” responses is considerably more reduced than that of “off” responses.
sues within the teratoma specimen, demonstrating tumor expression of retinal S antigen (Figure 6C). The patient’s serum was also autoreactive against normal rhesus monkey retina (Figure 6D). The patient’s vision and visual fields remained stable for 3 months after surgery without any further treatment. Comment. Teratomas are part of the larger family of dysgerminomas or germ cell tumors. Teratomas are composed of primitive cells that represent more than one germ layer and usually all 3. As the teratoma grows, these cells can differentiate along various germ lines, producing skin appendages, cartilage, bone, thyroid tissue, and any other tissue in the body.4 Teratomas usually originate in the hypothalamus or gonad but uncommonly arise in ectopic locations, including the orbit and mediastinum.5 This is the first report of paraneoplastic retinopathy associated with a mature teratoma. A previous report of retinal periphlebitis mimicking sarcoidosis in a child with a pineal germinoma proposed a paraneoplastic mechanism.6 Electronegative ERGs with abnormal on-responses are typically described in MAR and congenital stationary night blindness.7 The shimmering photopsias, nyctalopia, visual field constriction, and clinical appearance of the patient all were typical of MAR; however, metastatic workup failed to reveal evidence of melanoma or other occult malignancy, except for the me-
Figure 4. Computed tomographic scan demonstrates multicystic anterior mediastinal teratoma in the retrosternal position, anterior to the cardiac structures. A
B
Figure 5. Full-threshold Humphrey 30-2 visual fields, stimulus size V in both eyes after 3 rounds of periocular steroids. A, Right eye (no fixation losses or false-positive errors; false-negative errors, 2/18); B, left eye (fixation losses, 2/28; no false-positive errors; false-negative errors, 2/17).
diastinal teratoma. Malignant melanomas may arise de novo in teratomas.8,9 However, histopathological
(REPRINTED) ARCH OPHTHALMOL / VOL 121, JAN 2003 135
and immunochemical analyses did not demonstrate the presence of melanocytic elements. Expression of
WWW.ARCHOPHTHALMOL.COM
©2003 American Medical Association. All rights reserved. Downloaded From: http://archopht.jamanetwork.com/ by a National Institutes of Health User on 08/02/2013
†
‡
* § A
B GC
*
IPL
INL
OPL
ceptor layer, consistent with the presumed pathophysiologic mechanism of an immune response directed against retinal S antigen, which is localized to photoreceptor outer segments. However, the electrophysiologic data are contradictory, suggesting that the site of the major functional defect is proximal to the photoreceptor inner segments, as in MAR. Immunostaining was also present in the inner nuclear layer, albeit less conspicuously than in the photoreceptors. The peripheral retinal pigment epithelial depigmentation and visual field changes that occurred bilaterally may represent sequelae of autoimmune phenomena occurring in the overlying retina. We described a case of presumed paraneoplastic teratoma-associated retinopathy. This case suggests that benign tumors such as teratomas possibly may be associated with paraneoplastic retinopathy, which has previously been reported only as a sequelae of malignant neoplasms. Additional case reports and/or clinicopathologic investigations may assist in determining the mechanisms of visual loss in such cases.
ONL
Eric B. Suhler, MD Chi-Chao Chan, MD Rafael C. Caruso, MD David S. Schrump, MD Bethesda, Md Charles Thirkill, PhD Davis, Calif Janine A. Smith, MD Robert B. Nussenblatt, MD Ronald R. Buggage, MD Bethesda
PR C
D
Figure 6. Microphotography of the excised mature teratoma illustrates ectodermal structures (A), including pilosebaceous units and epithelial cells (arrow), and mesodermal structures, including collagen (asterisk), lymphoid tissue (dagger), smooth muscle (double dagger), and adipose tissue (section mark) (hematoxylin-eosin, original magnification ⫻100). Staining for HMB45 (B), an antigen present in all melanocytic cells, was negative, and staining was positive (C) for antiretinal S antigen in teratoma tissue, including pilosebaceous units (arrow) and mesenchymal cells (asterisk), confirming diffuse tumor expression of retinal S antigen (avidin-biotin complex immunoperoxidase, original magnification ⫻200). Immunostaining of paraffin-fixed normal rhesus monkey retina with patient sera as the primary antibody and rabbit-antihuman IgG as the secondary antibody (D) demonstrates positive staining of photoreceptors (arrows), as well as the inner (INL) and outer (ONL) nuclear layers and inner plexiform layer (IPL), corroborating the presence of an autoimmune retinopathy (immunofluorescent microscopy; antibody binding visualized using goat anti–human polyvalent immunoglobulin conjugated to fluorescein-isothiocyanate, original magnification ⫻200). Similar autofluorescence was obtained on immunostaining of the tumor section (not shown). GC indicates ganglion cell layer; OPL, outer plexiform layer; PR, photoreceptor cell layer.
retinal S antigen in the teratoma and staining of the normal primate photoreceptors with the patient’s serum support an association between the teratoma and the patient’s vision loss in this case of presumed paraneoplastic retinopathy. Although similar clinically and electrophysiologically to MAR, this case differs from the typical MAR presentation in a few notable ways. This
patient had bilateral vitritis as an initial sign, which has been reported in MAR; however, her objective and subjective visual field improvement with periocular corticosteroids are distinctly unusual for MAR. In addition, in MAR antiretinal antibodies are typically localized to bipolar cells, explaining the typical electronegative ERG.10 The most avid immunostaining in this case was in the photore-
(REPRINTED) ARCH OPHTHALMOL / VOL 121, JAN 2003 136
This study was supported in part by an unrestricted grant from Research to Prevent Blindness, Inc, New York, and core grant 1P30 EY12576-01 (Dr Thirkill) from the National Eye Institute, National Institutes of Health, Bethesda. The authors have no proprietary interest in the products described in this report. Corresponding author: Eric B. Suhler, MD, Ophthalmology Service, Portland Veterans’ Administration Medical Center, 3710 SW US Veterans’ Hospital Rd, Portland, OR 97207 (e-mail:
[email protected]). 1. Jacobsen DM. Paraneoplastic diseases of neuroophthalmic interest. In: Miller NR, Newman
WWW.ARCHOPHTHALMOL.COM
©2003 American Medical Association. All rights reserved. Downloaded From: http://archopht.jamanetwork.com/ by a National Institutes of Health User on 08/02/2013
2.
3. 4.
5. 6.
7.
8.
9. 10.
NC, eds. Walsh and Hoyt’s Clinical NeuroOphthalmology. 5th ed. Baltimore, Md: Williams & Wilkins; 1998:2497-2551. Whitcup SM, Vistica BA, Milam AH, Nussenblatt RB, Gery I. Recoverin-associated retinopathy: a clinically and immunologically distinctive disease. Am J Ophthalmol. 1998;126:230237. Marmor MF, Zrenner E. Standard for clinical electroretinography (1999 update). Doc Ophthalmol. 1998;97:143-156. Crum CP. Germ cell tumors. In: Cotran RS, Kumar V, Collins T, eds. Robbins Pathologic Basis of Disease. 6th ed. Philadelphia, Pa: WB Saunders Co; 1999:1073-1075. Dulmet EM, Macchiarini P, Suc B, Verley JM. Germ cell tumors of the mediastinum: a 30year experience. Cancer. 1993;72:1894-1901. Chang CW, Hay D, Chang TS, Nguyen R, Lyons CJ. Retinal periphlebitis in a patient with pineal germinoma. Arch Ophthalmol. 1999;117: 1434-1436. Alexander KR, Fishman GA, Peachey NS, Marchese AL, Tso MOM. “On” response defect in paraneoplastic night blindness with cutaneous malignant melanoma. Invest Ophthalmol Vis Sci. 1992;33:477-483. Davis GL. Malignant melanoma arising in mature ovarian cystic teratoma (dermoid cyst): report of 2 cases and literature analysis. Int J Gynecol Pathol. 1996;15:356-362. Liberati F, Maccio T, Ascani S, et al. Primary malignant melanoma arising in an ovarian cystic teratoma. Acta Oncol. 1998;37:381-383. Weinstein JM, Kelman SE, Bresnick GH, Kornguth SE. Paraneoplastic retinopathy associated with antiretinal bipolar cell antibodies in cutaneous malignant melanoma. Ophthalmology. 1994;101:1236-1243.
Isolated Anterior Uveitis as the Initial Sign of Systemic Candidemia
Endogenous fungal endophthalmitis may occur in both healthy and immunocompromised patients. Commonly, such patients have chorioretinal infiltration and a variable degree of posterior uveitis at the initial examination.1 Treatment is based on the severity of the disease and the response to treatment. We report a case of isolated iridocyclitis with a hypopyon secondary to Candida albicans infection. The atypical manifestation, diagnostic procedures, treatment, and outcome of this case are discussed. Report of a Case. A 14-year-old girl who underwent cardiac transplantation 4 months earlier was admitted with a 1-week history of fever of unknown origin. Her immunosuppressant medications at the time included tacrolimus and prednisone. In addition, she had been receiving intravenous immunoglobulins monthly through an indwelling catheter for hy-
Figure 1. A small iridolenticular fungal ball can be seen on the pupillary edge with posterior synechiae and white fluffy deposits on the anterior lens capsule.
pogammaglobulinemia. A workup included blood and urine cultures that were negative except for cytomegalovirus antigenemia. Ganciclovir treatment was started, and the patient was referred for an ophthalmic examination. Her corrected visual acuity was 20/50 OU. Low-grade anterior uveitis was noted in the left eye without evidence of vitritis or chorioretinitis. The patient denied any history of ocular trauma. Additional tests, including rapid plasma reagin, the hemagglutination treponemal test for syphilis, rheumatoid factor, antinuclear antibody levels, angiotensinconverting enzyme levels, HLA-B27 antigen, and chest radiography, were ordered, and the results of all tests were unremarkable. Six weeks later, the patient’s visual acuity had dropped to 20/200 OS, and she developed a hypopyon. Because of the progression of anterior uveitis despite topical steroid treatment and persistent fever, an anterior chamber tap and a lumbar puncture were recommended. Stains of the aqueous humor revealed 3 + polymorphonuclear neutrophil leukocytes with no organisms. Aqueous cultures grew C albicans. The cerebrospinal fluid showed a marked lymphocytic pleocytosis with increased protein but no growth. The patient was started on a regimen of intravenous amphotericin B, and
(REPRINTED) ARCH OPHTHALMOL / VOL 121, JAN 2003 137
topical fluconazole and ganciclovir treatments were discontinued. Postoperatively, fungal invasion of the iris and lens with formation of a fungal ball at the pupillary margin were noted (Figure 1). Another anterior chamber tap was performed and amphotericin B (5.0 µg) was injected into both the anterior chamber and vitreous, but the iridolenticular opacity persisted. Subsequently, because of lack of clinical response, pars plana vitrectomy, lensectomy, and excision of the involved iris with intravitreal amphotericin B (5.0 µg) were performed in the left eye. Intraoperatively, white fluffy material within the body of the crystalline lens and over the pars plana was noted and cultured. These findings prompted complete capsulectomy and aggressive vitreous base shaving with scleral depression. Intraoperative examination of the fundus did not show any involvement of the retina or choroid. Cultures obtained from the lens material and vitrectomy cassette were both positive for C albicans. The patient then underwent 2 additional administrations of intravitreal amphotericin B (5.0 µg) every 72 hours. The results of cultures from these procedures remained negative for organisms. After initiation of systemic treatment, the patient’s fever ceased, and
WWW.ARCHOPHTHALMOL.COM
©2003 American Medical Association. All rights reserved. Downloaded From: http://archopht.jamanetwork.com/ by a National Institutes of Health User on 08/02/2013
