Letters RESEARCH LETTER
Acquired Combined Hamartoma of the Retina and Retinal Pigment Epithelium The etiology of combined hamartoma of the retina and retinal pigment epithelium remains speculative, although the consensus has been that it is a congenital lesion present at birth, as inferred from the relatively early presentations of reported cases.1-3 We describe a patient with a combined hamartoma that developed from a focus of apparently normal retina, with concurrent serial fundus photographs. Report of a Case | A 6-month-old girl with an unremarkable medical and family history was referred for examination under anesthesia for a total tractional and exudative retinal detachment of the right eye. Findings on clinical examination of the left eye were unremarkable (Figure 1A). Widefield fluorescein angiography showed disorganized vascular branching in the right eye, with full vascularization in the left eye and normal posterior pole and midperipheral vasculature (Figure 1B). There were a total of 2 clock hours of atypical vascular patterns in the left eye in the far periphery, but with full perfusion. A diagnosis of familial exudative vitreoretinopathy was made, and the patient underwent surgery in the right eye. Examination under anesthesia 2 months postoperatively showed improvement in the right eye and continued normal findings on examination in the left eye. However, 3 months later, repeated examination of the left eye under anesthesia revealed a discrete lesion that was round, mildly raised, dark charcoal gray, and nasal to but not involving the disc, which was not present on prior examinations (Figure 2A). Preretinal glial proliferation
was present over the surface, and the surrounding retinal vasculature was contracted toward the lesion. Fluorescein angiography confirmed a tumor at the level of the retina and retinal pigment epithelium (Figure 2B), consistent with a presumed combined hamartoma of the retina and retinal pigment epithelium. Optical coherence tomography and ultrasonography were not performed, although they are not required for the diagnosis. Continued observation for 2 months more showed subtle growth of the tumor with additional gliosis. Discussion | Gass1 described 7 patients with combined hamartoma and synthesized his findings with previous reports, establishing a new clinical entity. He proposed that “they probably are present at birth, and they probably represent focal areas of maldevelopment of the pigment epithelium, retina, blood vessels, and overlying vitreous.”1 The youngest patient in his series was 19 months old.1 In the Macula Society’s subsequent collaborative report,2 the mean age was 15 years and the youngest patient was aged 10 months. Shields et al 3 described the youngest patient at age 2 weeks. This trend of early presentations seemed to validate Gass’ inference that these are congenital lesions present at birth. In contrast, we report a case in which a presumed combined hamartoma developed after birth—seemingly de novo— between ages 8 and 11 months. Although there are a few reports of acquired combined hamartomas,4-6 these previous cases involved distinct insults to regions that involved or were contiguous with areas that eventually developed hamartomas, such as optic disc edema 4,5 and vitreomacular traction 6 —suggesting, rather, that these lesions were acquired hamartomalike reactive gliosis and hyperpigmentation.6 Our patient has
Figure 1. Normal Baseline Fundus Photograph and Fluorescein Angiography A
B
Widefield color fundus photograph (A) and fluorescein angiography (B) demonstrate a normal posterior pole and nasal midperipheral retina in a 6-month-old girl. Findings on an examination 2 months later were also normal.
jamaophthalmology.com
(Reprinted) JAMA Ophthalmology September 2015 Volume 133, Number 9
Copyright 2015 American Medical Association. All rights reserved.
Downloaded From: http://archopht.jamanetwork.com/ by a United Arab Emirates University User on 06/26/2016
1085
Letters
Figure 2. Acquired Combined Hamartoma of the Retina and Retinal Pigment Epithelium A
B
A, Three months subsequently, a minimally raised, charcoal gray lesion with preretinal gliosis appeared in the previously normal retina. B, Fluorescein angiography shows that the retinal pigment epithelium, retina, and preretinal tissues were involved, with retinal vasculature contracting toward the lesion.
mild familial exudative vitreoretinopathy in the left eye, but the mild vascular changes are in the far periphery, well separated from the hamartoma, and the area that developed the lesion was fully vascularized and free of macroscopic damage or other inciting primary pathology. We cannot, of course, completely discount the influence of familial exudative vitreoretinopathy as presumed global wnt signaling aberrations, which, although unlikely, may have altered the timing of the hamartomatous growth. Additionally, we do not infer that all combined hamartomas are acquired; in considering the series by Shields et al,3 it is more likely that a hamartoma in a 2-week-old patient was indeed present at birth.4 In summary, we report a presumed combined hamartoma that was acquired after birth in a child whose fellow eye’s presentation allowed incidental observation of its development.
Role of the Funder/Sponsor: The Heed Ophthalmic Foundation had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication. Previous Presentation: This case was presented at the 2015 Atlantic Coast Retina Club Meeting; January 8, 2015; Boston, Massachusetts. 1. Gass JD. An unusual hamartoma of the pigment epithelium and retina simulating choroidal melanoma and retinoblastoma. Trans Am Ophthalmol Soc. 1973;71:171-185. 2. Schachat AP, Shields JA, Fine SL, et al. Combined hamartomas of the retina and retinal pigment epithelium. Ophthalmology. 1984;91(12):1609-1615. 3. Shields CL, Thangappan A, Hartzell K, Valente P, Pirondini C, Shields JA. Combined hamartoma of the retina and retinal pigment epithelium in 77 consecutive patients visual outcome based on macular versus extramacular tumor location. Ophthalmology. 2008;115(12):2246-2252.e3. 4. Hrisomalos NF, Mansour AM, Jampol LM, Fowell SM, Greenwald MJ. "Pseudo”-combined hamartoma following papilledema: case report. Arch Ophthalmol. 1987;105(12):1634-1635.
Yoshihiro Yonekawa, MD Benjamin J. Thomas, MD Kimberly A. Drenser, MD, PhD Michael T. Trese, MD Antonio Capone Jr, MD
5. Ticho BH, Egel RT, Jampol LM. Acquired combined hamartoma of the retina and pigment epithelium following parainfectious meningoencephalitis with optic neuritis. J Pediatr Ophthalmol Strabismus. 1998;35(2):116-118.
Author Affiliations: Associated Retinal Consultants, William Beaumont Hospital, Royal Oak, Michigan. Corresponding Author: Antonio Capone Jr, MD, Associated Retinal Consultants, William Beaumont Hospital, 3535 W 13th Mile Rd, Ste 344, Royal Oak, MI 48073 ([email protected]). Published Online: June 4, 2015. doi:10.1001/jamaophthalmol.2015.1675. Author Contributions: Dr Capone had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. Study concept and design: Yonekawa, Trese, Capone. Acquisition, analysis, or interpretation of data: Yonekawa, Thomas, Drenser, Capone. Drafting of the manuscript: Yonekawa, Trese. Critical revision of the manuscript for important intellectual content: Yonekawa, Thomas, Drenser, Capone. Administrative, technical, or material support: Capone. Study supervision: Drenser, Trese, Capone. Conflict of Interest Disclosures: All authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest and none were reported. 1086
Funding/Support: Dr Yonekawa is supported in part by the Heed Ophthalmic Foundation.
6. Singh AD, Agarwal A. Tumors of the retinal pigment epithelium. In: Agarwal A, ed. Gass’ Atlas of Macular Diseases. 5th ed. New York, NY: Saunders; 2012:1090-1091.
Retrospective Appraisal of Split-Cornea Transplantation: An Audit of 1141 Donor Corneas For more than 100 years, penetrating keratoplasty (PK) with fullthickness replacement of a diseased cornea with an allograft donor tissue has been successfully performed. Especially within the last 10 years, surgical techniques have been improved to the point that selective replacement of the diseased structure of the cornea is possible.1 Diseases of the corneal endothelium (eg, Fuchs endothelial dystrophy, pseudophakic bullous keratoplasty) are the main reasons for corneal transplantations2 and can be managed by Descemet stripping automated endothelial keratoplasty or Descemet membrane endothelial keratoplasty (DMEK).1,3,4 Deep anterior lamellar keratoplasty (DALK) allows selective replacement of the anterior pathologic corneal tissue (eg, advanced keratoconus, herpetic corneal
JAMA Ophthalmology September 2015 Volume 133, Number 9 (Reprinted)
Copyright 2015 American Medical Association. All rights reserved.
Downloaded From: http://archopht.jamanetwork.com/ by a United Arab Emirates University User on 06/26/2016
jamaophthalmology.com
Acquired Combined Hamartoma of the Retina and Retinal Pigment Epithelium The etiology of combined hamartoma of the retina and retinal pigment epithelium remains speculative, although the consensus has been that it is a congenital lesion present at birth, as inferred from the relatively early presentations of reported cases.1-3 We describe a patient with a combined hamartoma that developed from a focus of apparently normal retina, with concurrent serial fundus photographs. Report of a Case | A 6-month-old girl with an unremarkable medical and family history was referred for examination under anesthesia for a total tractional and exudative retinal detachment of the right eye. Findings on clinical examination of the left eye were unremarkable (Figure 1A). Widefield fluorescein angiography showed disorganized vascular branching in the right eye, with full vascularization in the left eye and normal posterior pole and midperipheral vasculature (Figure 1B). There were a total of 2 clock hours of atypical vascular patterns in the left eye in the far periphery, but with full perfusion. A diagnosis of familial exudative vitreoretinopathy was made, and the patient underwent surgery in the right eye. Examination under anesthesia 2 months postoperatively showed improvement in the right eye and continued normal findings on examination in the left eye. However, 3 months later, repeated examination of the left eye under anesthesia revealed a discrete lesion that was round, mildly raised, dark charcoal gray, and nasal to but not involving the disc, which was not present on prior examinations (Figure 2A). Preretinal glial proliferation
was present over the surface, and the surrounding retinal vasculature was contracted toward the lesion. Fluorescein angiography confirmed a tumor at the level of the retina and retinal pigment epithelium (Figure 2B), consistent with a presumed combined hamartoma of the retina and retinal pigment epithelium. Optical coherence tomography and ultrasonography were not performed, although they are not required for the diagnosis. Continued observation for 2 months more showed subtle growth of the tumor with additional gliosis. Discussion | Gass1 described 7 patients with combined hamartoma and synthesized his findings with previous reports, establishing a new clinical entity. He proposed that “they probably are present at birth, and they probably represent focal areas of maldevelopment of the pigment epithelium, retina, blood vessels, and overlying vitreous.”1 The youngest patient in his series was 19 months old.1 In the Macula Society’s subsequent collaborative report,2 the mean age was 15 years and the youngest patient was aged 10 months. Shields et al 3 described the youngest patient at age 2 weeks. This trend of early presentations seemed to validate Gass’ inference that these are congenital lesions present at birth. In contrast, we report a case in which a presumed combined hamartoma developed after birth—seemingly de novo— between ages 8 and 11 months. Although there are a few reports of acquired combined hamartomas,4-6 these previous cases involved distinct insults to regions that involved or were contiguous with areas that eventually developed hamartomas, such as optic disc edema 4,5 and vitreomacular traction 6 —suggesting, rather, that these lesions were acquired hamartomalike reactive gliosis and hyperpigmentation.6 Our patient has
Figure 1. Normal Baseline Fundus Photograph and Fluorescein Angiography A
B
Widefield color fundus photograph (A) and fluorescein angiography (B) demonstrate a normal posterior pole and nasal midperipheral retina in a 6-month-old girl. Findings on an examination 2 months later were also normal.
jamaophthalmology.com
(Reprinted) JAMA Ophthalmology September 2015 Volume 133, Number 9
Copyright 2015 American Medical Association. All rights reserved.
Downloaded From: http://archopht.jamanetwork.com/ by a United Arab Emirates University User on 06/26/2016
1085
Letters
Figure 2. Acquired Combined Hamartoma of the Retina and Retinal Pigment Epithelium A
B
A, Three months subsequently, a minimally raised, charcoal gray lesion with preretinal gliosis appeared in the previously normal retina. B, Fluorescein angiography shows that the retinal pigment epithelium, retina, and preretinal tissues were involved, with retinal vasculature contracting toward the lesion.
mild familial exudative vitreoretinopathy in the left eye, but the mild vascular changes are in the far periphery, well separated from the hamartoma, and the area that developed the lesion was fully vascularized and free of macroscopic damage or other inciting primary pathology. We cannot, of course, completely discount the influence of familial exudative vitreoretinopathy as presumed global wnt signaling aberrations, which, although unlikely, may have altered the timing of the hamartomatous growth. Additionally, we do not infer that all combined hamartomas are acquired; in considering the series by Shields et al,3 it is more likely that a hamartoma in a 2-week-old patient was indeed present at birth.4 In summary, we report a presumed combined hamartoma that was acquired after birth in a child whose fellow eye’s presentation allowed incidental observation of its development.
Role of the Funder/Sponsor: The Heed Ophthalmic Foundation had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication. Previous Presentation: This case was presented at the 2015 Atlantic Coast Retina Club Meeting; January 8, 2015; Boston, Massachusetts. 1. Gass JD. An unusual hamartoma of the pigment epithelium and retina simulating choroidal melanoma and retinoblastoma. Trans Am Ophthalmol Soc. 1973;71:171-185. 2. Schachat AP, Shields JA, Fine SL, et al. Combined hamartomas of the retina and retinal pigment epithelium. Ophthalmology. 1984;91(12):1609-1615. 3. Shields CL, Thangappan A, Hartzell K, Valente P, Pirondini C, Shields JA. Combined hamartoma of the retina and retinal pigment epithelium in 77 consecutive patients visual outcome based on macular versus extramacular tumor location. Ophthalmology. 2008;115(12):2246-2252.e3. 4. Hrisomalos NF, Mansour AM, Jampol LM, Fowell SM, Greenwald MJ. "Pseudo”-combined hamartoma following papilledema: case report. Arch Ophthalmol. 1987;105(12):1634-1635.
Yoshihiro Yonekawa, MD Benjamin J. Thomas, MD Kimberly A. Drenser, MD, PhD Michael T. Trese, MD Antonio Capone Jr, MD
5. Ticho BH, Egel RT, Jampol LM. Acquired combined hamartoma of the retina and pigment epithelium following parainfectious meningoencephalitis with optic neuritis. J Pediatr Ophthalmol Strabismus. 1998;35(2):116-118.
Author Affiliations: Associated Retinal Consultants, William Beaumont Hospital, Royal Oak, Michigan. Corresponding Author: Antonio Capone Jr, MD, Associated Retinal Consultants, William Beaumont Hospital, 3535 W 13th Mile Rd, Ste 344, Royal Oak, MI 48073 ([email protected]). Published Online: June 4, 2015. doi:10.1001/jamaophthalmol.2015.1675. Author Contributions: Dr Capone had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. Study concept and design: Yonekawa, Trese, Capone. Acquisition, analysis, or interpretation of data: Yonekawa, Thomas, Drenser, Capone. Drafting of the manuscript: Yonekawa, Trese. Critical revision of the manuscript for important intellectual content: Yonekawa, Thomas, Drenser, Capone. Administrative, technical, or material support: Capone. Study supervision: Drenser, Trese, Capone. Conflict of Interest Disclosures: All authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest and none were reported. 1086
Funding/Support: Dr Yonekawa is supported in part by the Heed Ophthalmic Foundation.
6. Singh AD, Agarwal A. Tumors of the retinal pigment epithelium. In: Agarwal A, ed. Gass’ Atlas of Macular Diseases. 5th ed. New York, NY: Saunders; 2012:1090-1091.
Retrospective Appraisal of Split-Cornea Transplantation: An Audit of 1141 Donor Corneas For more than 100 years, penetrating keratoplasty (PK) with fullthickness replacement of a diseased cornea with an allograft donor tissue has been successfully performed. Especially within the last 10 years, surgical techniques have been improved to the point that selective replacement of the diseased structure of the cornea is possible.1 Diseases of the corneal endothelium (eg, Fuchs endothelial dystrophy, pseudophakic bullous keratoplasty) are the main reasons for corneal transplantations2 and can be managed by Descemet stripping automated endothelial keratoplasty or Descemet membrane endothelial keratoplasty (DMEK).1,3,4 Deep anterior lamellar keratoplasty (DALK) allows selective replacement of the anterior pathologic corneal tissue (eg, advanced keratoconus, herpetic corneal
JAMA Ophthalmology September 2015 Volume 133, Number 9 (Reprinted)
Copyright 2015 American Medical Association. All rights reserved.
Downloaded From: http://archopht.jamanetwork.com/ by a United Arab Emirates University User on 06/26/2016
jamaophthalmology.com
