Letters
Published Online: September 18, 2014. doi:10.1001/jamaophthalmol.2014.3316.
Figure 2. Case 2
Conflict of Interest Disclosures: All authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest and none were reported.
A
1. Uchio E, Takeuchi S, Itoh N, Matsuura N, Ohno S, Aoki K. Clinical and epidemiological features of acute follicular conjunctivitis with special reference to that caused by herpes simplex virus type 1. Br J Ophthalmol. 2000;84(9): 968-972. 2. Ali R, Kim JY, Henderson BA. Adnexal and anterior segment manifestations of HIV/AIDS. Int Ophthalmol Clin. 2007;47(2):15-32. 3. Weinstein JE, Karp CL. Ocular surface neoplasias and human immunodeficiency virus infection. Curr Opin Infect Dis. 2013;26(1):58-65. 4. Husak R, Tebbe B, Goerdt S, et al. Pseudotumour of the tongue caused by herpes simplex virus type 2 in an HIV-1 infected immunosuppressed patient. Br J Dermatol. 1998;139(1):118-121. 5. Upadya A, Tilluckdharry L, Nagy CD, Ravichandran P, Manthous C. Endobronchial pseudo-tumour caused by herpes simplex. Eur Respir J. 2005;25 (6):1117-1120. B
Bilateral Exudative Retinal Detachment in a Diabetic Patient With Severe Peripheral Retinal Ischemia Diabetic macular edema can be resistant to anti–vascular endothelial growth factor (VEGF) therapy, and long-term consequences of VEGF suppression are not well understood.1 Previous studies in central retinal vein occlusion have associated exudative retinal detachment with increased production of VEGF and interleukin 6, 2 and localized central serous retinal detachment has been desc ribed in diabetic retinopathy.3,4 We observed a patient with chronic diffuse diabetic macular edema who developed extensive bilateral exudative retinal detachment after cessation of long-term anti-VEGF therapy.
C
A, Appearance of the conjunctival lesion on presentation. B, Hematoxylin-eosin staining of the biopsy specimen showing viral cytopathic features such as multinucleated giant cells and nuclear inclusions (original magnification ×10). C, Resolution of the lesion 1.5 years after presentation.
Author Affiliations: Department of Cornea and Refractive Surgery, Duke Eye Center, Durham, North Carolina (Vora); Department of Ophthalmic Oncology, Memorial Sloan Kettering Cancer Center, New York, New York (Marr); Department of Pathology, Duke Eye Center, Durham, North Carolina (Cummings); Department of Vitreoretinal Surgery and Ocular Oncology, Duke Eye Center, Durham, North Carolina (Mruthyunjaya). Corresponding Author: Prithvi Mruthyunjaya, MD, Duke Eye Center, 2351 Erwin Rd, Durham, NC 27705 ([email protected]).
Report of a Case | A woman in her early 70s with diabetes mellitus and hypertension but without nephropathy or peripheral edema was evaluated for decreasing vision bilaterally. She had a history of central retinal vein occlusion in the left eye, diabetic retinopathy in each eye with incomplete prior panretinal photocoagulation (PRP) in the right eye, and chronic diabetic macular edema in each eye that had become refractory to regular intravitreous anti-VEGF treatment. Anti-VEGF therapy was discontinued in favor of intravitreous triamcinolone acetonide injections 8 months earlier. After initial visual improvement, the patient noted gradual worsening of vision in both eyes. Visual acuity was 20/300 OD and 20/250 OS. Slitlamp examination demonstrated iris neovascularization in the left eye and pseudophakia in each eye. There was 2+ vitreous flare with trace anterior vitreous cell and no vitreous detachment in each eye. Fundus examination revealed diffuse macular edema and extensive retinal detachment with shifting subretinal fluid in each eye. An incomplete pattern of PRP scars was present in the right eye along with a large quantity of remnant triamcinolone in the inferotemporal vitreous gel in each eye (Figure 1). No retinal breaks or signs of posterior segment inflammation were identified. Wide-angle fluorescein angiography showed extensive peripheral nonperfusion in each eye with mild leakage from retinal vessels and no choroidal leakage (Figure 1).
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Figure 1. Preoperative Wide-Field Color Fundus Photographs and Fluorescein Angiograms A
B
C
D
Color fundus photographs show partial panretinal photocoagulation scars in the right eye (A), with exudative retinal detachment and preretinal triamcinolone acetonide particles inferiorly in both the right (A) and left (B) eyes. Late-phase
fluorescein angiograms reveal extensive peripheral retinal nonperfusion in the right (C) and left (D) eyes.
Figure 2. Postoperative Wide-Field Color Fundus Photographs A
B
The retina is attached and macular edema resolved 4 months postoperatively in the right eye (A) and 1 year postoperatively in the left eye (B).
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B-scan ultrasonography revealed no scleral or choroidal thickening or mass in either eye. The left eye underwent pars plana vitrectomy with peeling of the posterior hyaloid membrane, drainage retinotomy, fluid-gas exchange, and extensive endolaser PRP. This resulted in sustained retinal reattachment with resolution of iris neovascularization and macular edema (Figure 2). Visual acuity 1 year postoperatively was 20/150 OS. The right eye underwent a similar procedure and developed localized areas of epiretinal fibrosis postoperatively that resulted in traction retinal detachment involving the macula. Repeated vitrectomy with membrane peeling resulted in complete retinal reattachment, with visual acuity 4 months postoperatively measuring 20/600 OD (Figure 2). Discussion | This unusual case of bilateral exudative retinal detachment likely represents a VEGF-mediated process resulting from severe peripheral retinal ischemia associated with diabetic retinopathy and possibly central retinal vein occlusion. The differential diagnosis for bilateral exudative retinal detachment includes inflammatory disorders, malignant neoplasm, choroidal ischemia, uveal effusion syndrome, and central serous chorioretinopathy. These conditions were excluded by clinical examination, ancillary testing, and lack of response to intravitreal triamcinolone. Ultimately, pars plana vitrectomy was successfully used to reattach the retina and permit extensive PRP, thereby downregulating VEGF production and interrupting the pathogenic process. Long-term pharmacologic suppression of VEGF signaling is common in modern retina practice, but the long-term consequences of such treatment are not well understood. Hallmark signs of retinal ischemia such as neovascularization and vascular leakage are temporarily masked by regular anti-VEGF therapy. In our patient, withdrawal of anti-VEGF therapy might have exacerbated chronic retinal vascular leakage through a rebound effect, ultimately contributing to exudative retinal detachment; however, the precise role of anti-VEGF and corticosteroid injections in the pathogenesis of the exudative detachments is unclear. Further characterization of the vitreous proteome may improve our understanding of the underlying pathophysiology in such cases. It is possible that angiography-guided scatter photocoagulation to ischemic retina earlier in disease evolution may have prevented the detachments in our patient. Certainly, full PRP should be given prior to withdrawing anti-VEGF therapy in eyes with established proliferative diabetic retinopathy. Monica M. Michelotti, MD Nieraj Jain, MD Mark W. Johnson, MD Author Affiliations: Department of Ophthalmology and Visual Sciences, W. K. Kellogg Eye Center, University of Michigan, Ann Arbor. Corresponding Author: Mark W. Johnson, MD, Department of Ophthalmology and Visual Sciences, W. K. Kellogg Eye Center, University of Michigan, 1000 Wall St, Ann Arbor, MI 48105 ([email protected]). Published Online: September 25, 2014. doi:10.1001/jamaophthalmol.2014.3491.
Conflict of Interest Disclosures: All authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Dr Johnson reported serving as a Data and Safety Monitoring Committee member for GlaxoSmithKline and Oraya. No other disclosures were reported. Previous Presentation: This study was presented as a poster at the 13th International AMD and Retinal Congress of the European School for Advanced Studies in Ophthalmology; October 25-26, 2013; Dublin, Ireland. 1. Lanzetta P, Mitchell P, Wolf S, Veritti D. Different antivascular endothelial growth factor treatments and regimens and their outcomes in neovascular age-related macular degeneration: a literature review. Br J Ophthalmol. 2013;97 (12):1497-1507. 2. Noma H, Funatsu H, Mimura T, Harino S, Hori S. Vitreous levels of interleukin-6 and vascular endothelial growth factor in macular edema with central retinal vein occlusion. Ophthalmology. 2009;116(1):87-93. 3. Muraoka Y, Murakami T, Nishijima K, et al. Association between retinal venular dilation and serous retinal detachment in diabetic macular edema. Retina. 2014;34(4):725-731. 4. Koleva-Georgieva D, Sivkova N. Assessment of serous macular detachment in eyes with diabetic macular edema by use of spectral-domain optical coherence tomography. Graefes Arch Clin Exp Ophthalmol. 2009;247(11): 1461-1469.
Rapid Involution of Choroidal Metastasis Secondary to Renal Cell Carcinoma With Oral Sunitinib Oral sunitinib malate (Sutent) is a tyrosine kinase inhibitor that prevents binding of vascular endothelial growth factor and platelet-derived growth factor to their native receptors.1 It has been approved by the US Food and Drug Administration for the treatment of renal cell carcinoma (RCC) and imatinib mesylate– resistant gastrointestinal stromal tumor. Choroidal metastasis from RCC is rare, composing only 3% of all choroidal metastases.2 Herein, we report the first case, to our knowledge, of rapid involution of choroidal metastasis secondary to RCC using sunitinib. Report of a Case | A man in his early 50s was diagnosed as having right RCC and was treated with radical nephrectomy. Twenty-seven months later, he noticed intermittent photopsias and an inferior visual field defect in the left eye. Visual acuity was 20/25 OD and 20/20 OS. On examination, there was a 6.0 × 6.0 × 2.4-mm, predominantly amelanotic, orange, choroidal mass at the 12-o’clock position anterior to the equator in the left eye, with minimal associated subretinal fluid (Figure, A). Standardized echography demonstrated a dome-shaped lesion with high internal reflectivity and no internal vascularity (Figure, B). The patient had restaging workup the next month, and positron emission tomography and computed tomography showed left perihilar adenopathy and pulmonary nodules. Endobronchial ultrasonography and biopsy of a left perihilar mass confirmed metastatic RCC. The patient began treatment the following month with oral sunitinib malate, 50 mg once daily. The choroidal lesion in the left eye had grown slightly a month later (Figure, C and D), but the lesion showed appreciable involution by 3 months after beginning treatment (Figure, E and F). Six months following the start of treatment, the lesion measured 7.5 × 9.0 × 0.9 mm with only faint pigment epithelial changes (Figure, G and H). His symptoms and vision remained stable and his pulmonary metastases also
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Published Online: September 18, 2014. doi:10.1001/jamaophthalmol.2014.3316.
Figure 2. Case 2
Conflict of Interest Disclosures: All authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest and none were reported.
A
1. Uchio E, Takeuchi S, Itoh N, Matsuura N, Ohno S, Aoki K. Clinical and epidemiological features of acute follicular conjunctivitis with special reference to that caused by herpes simplex virus type 1. Br J Ophthalmol. 2000;84(9): 968-972. 2. Ali R, Kim JY, Henderson BA. Adnexal and anterior segment manifestations of HIV/AIDS. Int Ophthalmol Clin. 2007;47(2):15-32. 3. Weinstein JE, Karp CL. Ocular surface neoplasias and human immunodeficiency virus infection. Curr Opin Infect Dis. 2013;26(1):58-65. 4. Husak R, Tebbe B, Goerdt S, et al. Pseudotumour of the tongue caused by herpes simplex virus type 2 in an HIV-1 infected immunosuppressed patient. Br J Dermatol. 1998;139(1):118-121. 5. Upadya A, Tilluckdharry L, Nagy CD, Ravichandran P, Manthous C. Endobronchial pseudo-tumour caused by herpes simplex. Eur Respir J. 2005;25 (6):1117-1120. B
Bilateral Exudative Retinal Detachment in a Diabetic Patient With Severe Peripheral Retinal Ischemia Diabetic macular edema can be resistant to anti–vascular endothelial growth factor (VEGF) therapy, and long-term consequences of VEGF suppression are not well understood.1 Previous studies in central retinal vein occlusion have associated exudative retinal detachment with increased production of VEGF and interleukin 6, 2 and localized central serous retinal detachment has been desc ribed in diabetic retinopathy.3,4 We observed a patient with chronic diffuse diabetic macular edema who developed extensive bilateral exudative retinal detachment after cessation of long-term anti-VEGF therapy.
C
A, Appearance of the conjunctival lesion on presentation. B, Hematoxylin-eosin staining of the biopsy specimen showing viral cytopathic features such as multinucleated giant cells and nuclear inclusions (original magnification ×10). C, Resolution of the lesion 1.5 years after presentation.
Author Affiliations: Department of Cornea and Refractive Surgery, Duke Eye Center, Durham, North Carolina (Vora); Department of Ophthalmic Oncology, Memorial Sloan Kettering Cancer Center, New York, New York (Marr); Department of Pathology, Duke Eye Center, Durham, North Carolina (Cummings); Department of Vitreoretinal Surgery and Ocular Oncology, Duke Eye Center, Durham, North Carolina (Mruthyunjaya). Corresponding Author: Prithvi Mruthyunjaya, MD, Duke Eye Center, 2351 Erwin Rd, Durham, NC 27705 ([email protected]).
Report of a Case | A woman in her early 70s with diabetes mellitus and hypertension but without nephropathy or peripheral edema was evaluated for decreasing vision bilaterally. She had a history of central retinal vein occlusion in the left eye, diabetic retinopathy in each eye with incomplete prior panretinal photocoagulation (PRP) in the right eye, and chronic diabetic macular edema in each eye that had become refractory to regular intravitreous anti-VEGF treatment. Anti-VEGF therapy was discontinued in favor of intravitreous triamcinolone acetonide injections 8 months earlier. After initial visual improvement, the patient noted gradual worsening of vision in both eyes. Visual acuity was 20/300 OD and 20/250 OS. Slitlamp examination demonstrated iris neovascularization in the left eye and pseudophakia in each eye. There was 2+ vitreous flare with trace anterior vitreous cell and no vitreous detachment in each eye. Fundus examination revealed diffuse macular edema and extensive retinal detachment with shifting subretinal fluid in each eye. An incomplete pattern of PRP scars was present in the right eye along with a large quantity of remnant triamcinolone in the inferotemporal vitreous gel in each eye (Figure 1). No retinal breaks or signs of posterior segment inflammation were identified. Wide-angle fluorescein angiography showed extensive peripheral nonperfusion in each eye with mild leakage from retinal vessels and no choroidal leakage (Figure 1).
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Figure 1. Preoperative Wide-Field Color Fundus Photographs and Fluorescein Angiograms A
B
C
D
Color fundus photographs show partial panretinal photocoagulation scars in the right eye (A), with exudative retinal detachment and preretinal triamcinolone acetonide particles inferiorly in both the right (A) and left (B) eyes. Late-phase
fluorescein angiograms reveal extensive peripheral retinal nonperfusion in the right (C) and left (D) eyes.
Figure 2. Postoperative Wide-Field Color Fundus Photographs A
B
The retina is attached and macular edema resolved 4 months postoperatively in the right eye (A) and 1 year postoperatively in the left eye (B).
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B-scan ultrasonography revealed no scleral or choroidal thickening or mass in either eye. The left eye underwent pars plana vitrectomy with peeling of the posterior hyaloid membrane, drainage retinotomy, fluid-gas exchange, and extensive endolaser PRP. This resulted in sustained retinal reattachment with resolution of iris neovascularization and macular edema (Figure 2). Visual acuity 1 year postoperatively was 20/150 OS. The right eye underwent a similar procedure and developed localized areas of epiretinal fibrosis postoperatively that resulted in traction retinal detachment involving the macula. Repeated vitrectomy with membrane peeling resulted in complete retinal reattachment, with visual acuity 4 months postoperatively measuring 20/600 OD (Figure 2). Discussion | This unusual case of bilateral exudative retinal detachment likely represents a VEGF-mediated process resulting from severe peripheral retinal ischemia associated with diabetic retinopathy and possibly central retinal vein occlusion. The differential diagnosis for bilateral exudative retinal detachment includes inflammatory disorders, malignant neoplasm, choroidal ischemia, uveal effusion syndrome, and central serous chorioretinopathy. These conditions were excluded by clinical examination, ancillary testing, and lack of response to intravitreal triamcinolone. Ultimately, pars plana vitrectomy was successfully used to reattach the retina and permit extensive PRP, thereby downregulating VEGF production and interrupting the pathogenic process. Long-term pharmacologic suppression of VEGF signaling is common in modern retina practice, but the long-term consequences of such treatment are not well understood. Hallmark signs of retinal ischemia such as neovascularization and vascular leakage are temporarily masked by regular anti-VEGF therapy. In our patient, withdrawal of anti-VEGF therapy might have exacerbated chronic retinal vascular leakage through a rebound effect, ultimately contributing to exudative retinal detachment; however, the precise role of anti-VEGF and corticosteroid injections in the pathogenesis of the exudative detachments is unclear. Further characterization of the vitreous proteome may improve our understanding of the underlying pathophysiology in such cases. It is possible that angiography-guided scatter photocoagulation to ischemic retina earlier in disease evolution may have prevented the detachments in our patient. Certainly, full PRP should be given prior to withdrawing anti-VEGF therapy in eyes with established proliferative diabetic retinopathy. Monica M. Michelotti, MD Nieraj Jain, MD Mark W. Johnson, MD Author Affiliations: Department of Ophthalmology and Visual Sciences, W. K. Kellogg Eye Center, University of Michigan, Ann Arbor. Corresponding Author: Mark W. Johnson, MD, Department of Ophthalmology and Visual Sciences, W. K. Kellogg Eye Center, University of Michigan, 1000 Wall St, Ann Arbor, MI 48105 ([email protected]). Published Online: September 25, 2014. doi:10.1001/jamaophthalmol.2014.3491.
Conflict of Interest Disclosures: All authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Dr Johnson reported serving as a Data and Safety Monitoring Committee member for GlaxoSmithKline and Oraya. No other disclosures were reported. Previous Presentation: This study was presented as a poster at the 13th International AMD and Retinal Congress of the European School for Advanced Studies in Ophthalmology; October 25-26, 2013; Dublin, Ireland. 1. Lanzetta P, Mitchell P, Wolf S, Veritti D. Different antivascular endothelial growth factor treatments and regimens and their outcomes in neovascular age-related macular degeneration: a literature review. Br J Ophthalmol. 2013;97 (12):1497-1507. 2. Noma H, Funatsu H, Mimura T, Harino S, Hori S. Vitreous levels of interleukin-6 and vascular endothelial growth factor in macular edema with central retinal vein occlusion. Ophthalmology. 2009;116(1):87-93. 3. Muraoka Y, Murakami T, Nishijima K, et al. Association between retinal venular dilation and serous retinal detachment in diabetic macular edema. Retina. 2014;34(4):725-731. 4. Koleva-Georgieva D, Sivkova N. Assessment of serous macular detachment in eyes with diabetic macular edema by use of spectral-domain optical coherence tomography. Graefes Arch Clin Exp Ophthalmol. 2009;247(11): 1461-1469.
Rapid Involution of Choroidal Metastasis Secondary to Renal Cell Carcinoma With Oral Sunitinib Oral sunitinib malate (Sutent) is a tyrosine kinase inhibitor that prevents binding of vascular endothelial growth factor and platelet-derived growth factor to their native receptors.1 It has been approved by the US Food and Drug Administration for the treatment of renal cell carcinoma (RCC) and imatinib mesylate– resistant gastrointestinal stromal tumor. Choroidal metastasis from RCC is rare, composing only 3% of all choroidal metastases.2 Herein, we report the first case, to our knowledge, of rapid involution of choroidal metastasis secondary to RCC using sunitinib. Report of a Case | A man in his early 50s was diagnosed as having right RCC and was treated with radical nephrectomy. Twenty-seven months later, he noticed intermittent photopsias and an inferior visual field defect in the left eye. Visual acuity was 20/25 OD and 20/20 OS. On examination, there was a 6.0 × 6.0 × 2.4-mm, predominantly amelanotic, orange, choroidal mass at the 12-o’clock position anterior to the equator in the left eye, with minimal associated subretinal fluid (Figure, A). Standardized echography demonstrated a dome-shaped lesion with high internal reflectivity and no internal vascularity (Figure, B). The patient had restaging workup the next month, and positron emission tomography and computed tomography showed left perihilar adenopathy and pulmonary nodules. Endobronchial ultrasonography and biopsy of a left perihilar mass confirmed metastatic RCC. The patient began treatment the following month with oral sunitinib malate, 50 mg once daily. The choroidal lesion in the left eye had grown slightly a month later (Figure, C and D), but the lesion showed appreciable involution by 3 months after beginning treatment (Figure, E and F). Six months following the start of treatment, the lesion measured 7.5 × 9.0 × 0.9 mm with only faint pigment epithelial changes (Figure, G and H). His symptoms and vision remained stable and his pulmonary metastases also
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![[Bilateral exudative retinal detachment as presenting sign of preeclampsia].](/assets/img/hold.png)
