Diagnostic and Therapeutic Challenges
Edited by H. Richard McDonald
Dr. Xiao Yong Huang, Dr. Tongtao Zhao, Xi Yu Bachelor, Dr. Audina M. Berrocal, and Dr. Vishak John
T
eyes. Fluorescein angiography showed temporal peripheral nonperfusion and exudation in the right eye and extensive nonperfusion temporally in the left eye. The patient underwent workup for basic inflammatory conditions including toxocara, Lyme, and syphilis, which were all negative. There was no known family history of any eye disease, although fluorescein angiography was not performed in family members. The differential diagnosis of this presentation includes primary retinal diseases, such as familial exudative vitreoretinopathy (FEVR), retinopathy of prematurity, x-linked retinoschisis, and Coats disease, multisystem conditions, such as Norrie disease, incontinentia pigmenti, and fascioscapulohumeral muscular dystrophy syndrome, and inflammatory conditions, such as toxocariasis and Eale disease. Rare diseases that present with avascularity and a Coats-like response such as retinitis pigmentosa can be considered. Although a diagnosis of FEVR should be considered in our patient, the lack of ocular manifestations before his age of presentation is unusual. To confirm the diagnosis of FEVR, fluorescein angiography of family members is important. An extensive genetic workup should be undertaken. Genetic workup for FEVR includes the FZD4, LRP5, and NDP gene sequencing. The fascioscapulohumeral syndrome is also autosomal dominant condition, and genetic evaluation should also be undertaken after a clinical examination of the patient’s scapula is performed. Incontinentia pigmenti, an x-linked dominant disease, is considered lethal in males, and therefore unlikely in this male patient. Yet, cases have been reported of male patients with incontinentia pigmenti due to 47 XXY karyotype or somatic mosaicism.1 Retinopathy of prematurity is in the differential, but this patient was born at full term. We have seen patients with myopia and nonperfusion of the retina with a previous history of untreated/regressed retinopathy of prematurity. Toxocariasis has been ruled out because
his case is submitted by Dr. Xiao Yong Huang, Dr. Tongtao Zhao, and Xi Yu Bachelor of the Southwest Hospital/Southwest Eye Hospital, Third Military Medical University, Chongqing, China; commented by Dr. Audina M. Berrocal and Dr. Vishak John, Miami, Florida. Case Report
A 37-year-old man was admitted to our hospital with a 6-month history of visual loss in the right eye and a 3-month history of visual loss in the left eye. He was the product of a full-term uncomplicated delivery. Visual acuity was hand motion in both eyes and could not be corrected. Intraocular pressures measured 13 mmHg in the right eye and 14 mmHg in the left eye. The lenses showed mild clouding. Binocular indirect ophthalmoscopy revealed Stage D proliferative vitreoretinopathy with retinal dragging temporally from falciform folds and moderate foveal dragging in the right eye and bullous retinal detachment in the left eye (Figure 1, B, C, and E). Fluorescein angiography of both eyes disclosed temporal peripheral nonperfusion and diffused exudation in the right eye and V-shaped nonperfusion temporally in the left eye (Figure 1, A and D). Axial length was 29.1 mm in the right eye and 28.3 mm in the left eye. B-scan ultrasonography showed total exudative retinal detachment in both eyes (Figure 1, F and G). Workup for uveitis or inflammatory disease including toxocara, Lyme, and syphilis were all negative. Complete blood count and hemoglobin electrophoresis were normal. Chest x-rays were normal. His father died 7 years ago, and his mother and old brother were examined and found to be free of any retinal disease. This case is presented for the discussion of prognosis and treatment.
Dr. Audina M. Berrocal and Dr. Vishak John (Miami, Florida): In this month’s edition of Retina, Huang et al from Chongqing, China, present a case of a 37-year-old man with bilateral vision loss and exudative vitreoretinopathy. A product of full-term uncomplicated birth, the patient presented with hand motions vision bilaterally associated with exudative retinal detachments in both 2657
2658 RETINA, THE JOURNAL OF RETINAL AND VITREOUS DISEASES
2015 VOLUME 35 NUMBER 12
Fig. 1. Severe familial exudative vitreoretinopathy. A. Fluorescein angiography of the right eye disclosed temporal peripheral nonperfusion and diffused exudation. Note the leakage from neovascularization at the border of the vascularized and avascular retina. B. Ophthalmoscopy revealed proliferative vitreoretinopathy with moderate foveal dragging in the right eye. C. Ophthalmoscopy revealed retinal dragging temporally from falciform folds in the right eye. D. Fluorescein angiography showed V-shaped nonperfusion temporally in the left eye. E. Ophthalmoscopy revealed bullous retinal detachment in the left eye. F. B-scan showed funnel retinal detachment in the right eye. G. B-scan showed total retinal detachment in the left eye.
of the dragging of the vasculature, and the retinal detachment should be in the differential, although bilateral toxocariasis is rare but has been reported.2 Coats disease can also present with nonperfusion and exudative detachments but unlikely in this presentation. Coats plus disease manifests as bilateral exudative detachments, but presentation is much earlier in life with associated brain findings and mental retardation. X-linked retinoschisis can exhibit retinal detachments and peripheral avascularity, but macular dragging is not seen. Coats-like response has been seen in retinitis pigmentosa (RP) and Leber’s congenital amaurosis, but there are no signs of those diseases in this patient. The vasculature is healthy appearing with no attenuation.
The next large category of differential diagnosis for this presentation should be inflammatory conditions. Vogt–Koyanagi–Harada syndrome, sympathetic ophthalmia, and atypical central serous chorioretinopathy all can present with extensive exudative retinal detachments similar to the one seen in this patient. In this male patient, Norrie disease can also be on the differential, and therefore, genetic testing can be pursued on that front as well. The role of high myopia in this clinical picture is not clear cut. Although it has been noted in literature that patients with FEVR can have pathologic myopia associated with the condition, the underlying pathophysiology of that association is not well understood. Patients with
2659
DIAGNOSTIC AND THERAPEUTIC CHALLENGES
myopia can have avascular peripheral retina in some cases, but the extensive neovascularization is uncommon from just pathologic myopia.3 Although the evaluation of the etiology is being undertaken, the management for this condition should be stepwise. We recommend starting with laser-guided treatment of the attached retina and injection of offlabel anti-vascular endothelial growth factor (VEGF) agents. The patient needs to be watched closely, and serial angiograms with angiogram-guided laser treatments and intravitreal treatments should be performed. Anti-VEGF injection should be pursued along with subTenon’s steroids, concurrent to the laser, to reduce both the neovascular and the inflammatory component. Finally, if the detachments in the eyes do not show any improvement after aggressive nonsurgical treatment, then intraocular surgery should be considered. Although intraocular surgery for exudative retinal detachments can be controversial, in a case of FEVR, there tends to be a significant tractional and neovascular component to the exudative detachment. In a recalcitrant case, we recommend pars plana vitrectomy, scleral buckle, external drainage, laser and silicone oil tamponade along with intravitreal anti-VEGF, and a posterior sub-Tenon’s steroid injection.4 Removal of the posterior hyaloid is recommended especially if there is a marked tractional component sometimes not noticed clinically. Staining with diluted intravitreal steroid is recommended for successful removal of the posterior hyaloid. A consistent and aggressive management approach of these complex cases is recommended. Editor’s Note: Dr. Huang, Dr. Zhao, and Xi Yu Bachelor have presented a man with bilateral visual loss of several months duration. Retinal examination revealed proliferative vitreoretinopathy in one eye and bullous retinal detachment in the other. Dr. Audina M. Berrocal reviews this case and has developed a differential diagnosis for a patient with these findings: I. Genetic/congenital A. Familial exudative vitreoretinopathy B. Retinopathy of prematurity C. X-linked retinoschisis D. Coats disease E. Norrie disease F. Incontinentia pigmenti G. Fascioscapulohumeral dystrophy II. Inflammatory A. Toxocariasis B. Eale disease C. Retinitis pigmentosa
D. Vogt–Koyanagi–Harada syndrome E. Sympathetic ophthalmia III. Idiopathic A. Atypical central serous retinopathy She recommends fluorescein angiography of family members to help pinpoint the mode of inheritance if FEVR is suspected. A genetic workup for FEVR should include FZD4, LRP5, and NDP gene sequencing. She reviews each of the other possibilities in her differential diagnosis. Dr. Berrocal addresses the management of this patient while the extensive genetic testing is underway. She recommends laser treatment, anti-VEGF intraocular injections, and sub-Tenon’s steroids. If the exudative component does not improve, she calls for surgical intervention. This includes vitrectomy, scleral buckling, external drainage, endolaser photocoagulation, silicone oil tamponade along with intravitreal anti-VEGF, and posterior sub-Tenon’s steroids. We thank Dr. Berrocal and Dr. John for their analysis, and Dr. Huang, Dr. Zhao, and Xi Yu Bachelor for their case. Acknowledgements This work was supported by Nature Science Foundation of China (31071202), National key basic research program of China (No. 2013CB967001) and Clinical Foundation of Southwest Hospital (SWH2014LC12). References 1. Kenwrick S, Woffendin H, Jakins T, et al. Survival of male patients with incontinentia pigmenti carrying a lethal mutation can be explained by somatic mosaicism or Klinefelter syndrome. Am J Hum Genet 2001;69:1210–1217. 2. Benitez del Castillo JM, Herreros G, Guillen JL, et al. Bilateral ocular toxocariasis demonstrated by aqueous humor enzymelinked immunosorbent assay. Am J Ophthalmol 1995;119:514–516. 3. Yang CI, Chen SN, Yang ML. Excessive myopia and anisometropia associated with familial exudative vitreoretinopathy. Chang Gung Med J 2002;25:388–392. 4. John VJ, Mandelcorn ED, Albini TA. Internal drainage for chronic macula-involving serous retinal detachment in idiopathic central serous chorioretinopathy. Int Ophthalmol 2014; 34:91–95.
RETINAÒ, The Journal of Retinal and Vitreous Diseases, encourages readers to submit Diagnostic and Therapeutic Challenges to [email protected]. Cases for the Diagnostic and Therapeutic Challenges section should include a detailed history of the patient, the diagnosis, the workup, the management, and finally, the question or questions that the submitter wishes to have answered by the consultants.
Edited by H. Richard McDonald
Dr. Xiao Yong Huang, Dr. Tongtao Zhao, Xi Yu Bachelor, Dr. Audina M. Berrocal, and Dr. Vishak John
T
eyes. Fluorescein angiography showed temporal peripheral nonperfusion and exudation in the right eye and extensive nonperfusion temporally in the left eye. The patient underwent workup for basic inflammatory conditions including toxocara, Lyme, and syphilis, which were all negative. There was no known family history of any eye disease, although fluorescein angiography was not performed in family members. The differential diagnosis of this presentation includes primary retinal diseases, such as familial exudative vitreoretinopathy (FEVR), retinopathy of prematurity, x-linked retinoschisis, and Coats disease, multisystem conditions, such as Norrie disease, incontinentia pigmenti, and fascioscapulohumeral muscular dystrophy syndrome, and inflammatory conditions, such as toxocariasis and Eale disease. Rare diseases that present with avascularity and a Coats-like response such as retinitis pigmentosa can be considered. Although a diagnosis of FEVR should be considered in our patient, the lack of ocular manifestations before his age of presentation is unusual. To confirm the diagnosis of FEVR, fluorescein angiography of family members is important. An extensive genetic workup should be undertaken. Genetic workup for FEVR includes the FZD4, LRP5, and NDP gene sequencing. The fascioscapulohumeral syndrome is also autosomal dominant condition, and genetic evaluation should also be undertaken after a clinical examination of the patient’s scapula is performed. Incontinentia pigmenti, an x-linked dominant disease, is considered lethal in males, and therefore unlikely in this male patient. Yet, cases have been reported of male patients with incontinentia pigmenti due to 47 XXY karyotype or somatic mosaicism.1 Retinopathy of prematurity is in the differential, but this patient was born at full term. We have seen patients with myopia and nonperfusion of the retina with a previous history of untreated/regressed retinopathy of prematurity. Toxocariasis has been ruled out because
his case is submitted by Dr. Xiao Yong Huang, Dr. Tongtao Zhao, and Xi Yu Bachelor of the Southwest Hospital/Southwest Eye Hospital, Third Military Medical University, Chongqing, China; commented by Dr. Audina M. Berrocal and Dr. Vishak John, Miami, Florida. Case Report
A 37-year-old man was admitted to our hospital with a 6-month history of visual loss in the right eye and a 3-month history of visual loss in the left eye. He was the product of a full-term uncomplicated delivery. Visual acuity was hand motion in both eyes and could not be corrected. Intraocular pressures measured 13 mmHg in the right eye and 14 mmHg in the left eye. The lenses showed mild clouding. Binocular indirect ophthalmoscopy revealed Stage D proliferative vitreoretinopathy with retinal dragging temporally from falciform folds and moderate foveal dragging in the right eye and bullous retinal detachment in the left eye (Figure 1, B, C, and E). Fluorescein angiography of both eyes disclosed temporal peripheral nonperfusion and diffused exudation in the right eye and V-shaped nonperfusion temporally in the left eye (Figure 1, A and D). Axial length was 29.1 mm in the right eye and 28.3 mm in the left eye. B-scan ultrasonography showed total exudative retinal detachment in both eyes (Figure 1, F and G). Workup for uveitis or inflammatory disease including toxocara, Lyme, and syphilis were all negative. Complete blood count and hemoglobin electrophoresis were normal. Chest x-rays were normal. His father died 7 years ago, and his mother and old brother were examined and found to be free of any retinal disease. This case is presented for the discussion of prognosis and treatment.
Dr. Audina M. Berrocal and Dr. Vishak John (Miami, Florida): In this month’s edition of Retina, Huang et al from Chongqing, China, present a case of a 37-year-old man with bilateral vision loss and exudative vitreoretinopathy. A product of full-term uncomplicated birth, the patient presented with hand motions vision bilaterally associated with exudative retinal detachments in both 2657
2658 RETINA, THE JOURNAL OF RETINAL AND VITREOUS DISEASES
2015 VOLUME 35 NUMBER 12
Fig. 1. Severe familial exudative vitreoretinopathy. A. Fluorescein angiography of the right eye disclosed temporal peripheral nonperfusion and diffused exudation. Note the leakage from neovascularization at the border of the vascularized and avascular retina. B. Ophthalmoscopy revealed proliferative vitreoretinopathy with moderate foveal dragging in the right eye. C. Ophthalmoscopy revealed retinal dragging temporally from falciform folds in the right eye. D. Fluorescein angiography showed V-shaped nonperfusion temporally in the left eye. E. Ophthalmoscopy revealed bullous retinal detachment in the left eye. F. B-scan showed funnel retinal detachment in the right eye. G. B-scan showed total retinal detachment in the left eye.
of the dragging of the vasculature, and the retinal detachment should be in the differential, although bilateral toxocariasis is rare but has been reported.2 Coats disease can also present with nonperfusion and exudative detachments but unlikely in this presentation. Coats plus disease manifests as bilateral exudative detachments, but presentation is much earlier in life with associated brain findings and mental retardation. X-linked retinoschisis can exhibit retinal detachments and peripheral avascularity, but macular dragging is not seen. Coats-like response has been seen in retinitis pigmentosa (RP) and Leber’s congenital amaurosis, but there are no signs of those diseases in this patient. The vasculature is healthy appearing with no attenuation.
The next large category of differential diagnosis for this presentation should be inflammatory conditions. Vogt–Koyanagi–Harada syndrome, sympathetic ophthalmia, and atypical central serous chorioretinopathy all can present with extensive exudative retinal detachments similar to the one seen in this patient. In this male patient, Norrie disease can also be on the differential, and therefore, genetic testing can be pursued on that front as well. The role of high myopia in this clinical picture is not clear cut. Although it has been noted in literature that patients with FEVR can have pathologic myopia associated with the condition, the underlying pathophysiology of that association is not well understood. Patients with
2659
DIAGNOSTIC AND THERAPEUTIC CHALLENGES
myopia can have avascular peripheral retina in some cases, but the extensive neovascularization is uncommon from just pathologic myopia.3 Although the evaluation of the etiology is being undertaken, the management for this condition should be stepwise. We recommend starting with laser-guided treatment of the attached retina and injection of offlabel anti-vascular endothelial growth factor (VEGF) agents. The patient needs to be watched closely, and serial angiograms with angiogram-guided laser treatments and intravitreal treatments should be performed. Anti-VEGF injection should be pursued along with subTenon’s steroids, concurrent to the laser, to reduce both the neovascular and the inflammatory component. Finally, if the detachments in the eyes do not show any improvement after aggressive nonsurgical treatment, then intraocular surgery should be considered. Although intraocular surgery for exudative retinal detachments can be controversial, in a case of FEVR, there tends to be a significant tractional and neovascular component to the exudative detachment. In a recalcitrant case, we recommend pars plana vitrectomy, scleral buckle, external drainage, laser and silicone oil tamponade along with intravitreal anti-VEGF, and a posterior sub-Tenon’s steroid injection.4 Removal of the posterior hyaloid is recommended especially if there is a marked tractional component sometimes not noticed clinically. Staining with diluted intravitreal steroid is recommended for successful removal of the posterior hyaloid. A consistent and aggressive management approach of these complex cases is recommended. Editor’s Note: Dr. Huang, Dr. Zhao, and Xi Yu Bachelor have presented a man with bilateral visual loss of several months duration. Retinal examination revealed proliferative vitreoretinopathy in one eye and bullous retinal detachment in the other. Dr. Audina M. Berrocal reviews this case and has developed a differential diagnosis for a patient with these findings: I. Genetic/congenital A. Familial exudative vitreoretinopathy B. Retinopathy of prematurity C. X-linked retinoschisis D. Coats disease E. Norrie disease F. Incontinentia pigmenti G. Fascioscapulohumeral dystrophy II. Inflammatory A. Toxocariasis B. Eale disease C. Retinitis pigmentosa
D. Vogt–Koyanagi–Harada syndrome E. Sympathetic ophthalmia III. Idiopathic A. Atypical central serous retinopathy She recommends fluorescein angiography of family members to help pinpoint the mode of inheritance if FEVR is suspected. A genetic workup for FEVR should include FZD4, LRP5, and NDP gene sequencing. She reviews each of the other possibilities in her differential diagnosis. Dr. Berrocal addresses the management of this patient while the extensive genetic testing is underway. She recommends laser treatment, anti-VEGF intraocular injections, and sub-Tenon’s steroids. If the exudative component does not improve, she calls for surgical intervention. This includes vitrectomy, scleral buckling, external drainage, endolaser photocoagulation, silicone oil tamponade along with intravitreal anti-VEGF, and posterior sub-Tenon’s steroids. We thank Dr. Berrocal and Dr. John for their analysis, and Dr. Huang, Dr. Zhao, and Xi Yu Bachelor for their case. Acknowledgements This work was supported by Nature Science Foundation of China (31071202), National key basic research program of China (No. 2013CB967001) and Clinical Foundation of Southwest Hospital (SWH2014LC12). References 1. Kenwrick S, Woffendin H, Jakins T, et al. Survival of male patients with incontinentia pigmenti carrying a lethal mutation can be explained by somatic mosaicism or Klinefelter syndrome. Am J Hum Genet 2001;69:1210–1217. 2. Benitez del Castillo JM, Herreros G, Guillen JL, et al. Bilateral ocular toxocariasis demonstrated by aqueous humor enzymelinked immunosorbent assay. Am J Ophthalmol 1995;119:514–516. 3. Yang CI, Chen SN, Yang ML. Excessive myopia and anisometropia associated with familial exudative vitreoretinopathy. Chang Gung Med J 2002;25:388–392. 4. John VJ, Mandelcorn ED, Albini TA. Internal drainage for chronic macula-involving serous retinal detachment in idiopathic central serous chorioretinopathy. Int Ophthalmol 2014; 34:91–95.
RETINAÒ, The Journal of Retinal and Vitreous Diseases, encourages readers to submit Diagnostic and Therapeutic Challenges to [email protected]. Cases for the Diagnostic and Therapeutic Challenges section should include a detailed history of the patient, the diagnosis, the workup, the management, and finally, the question or questions that the submitter wishes to have answered by the consultants.
