Peripapillary choroidal neovascularization in pars planitis
© Mehta et al.; licensee Springer. 2013
Received: 11 September 2012
Accepted: 12 September 2012
Published: 15 January 2013
Choroidal neovascularization (CNV) is a rare complication of intermediate uveitis. Risk factors are not well-characterized. Here, we describe a case of peripapillary CNV in a patient with intermediate uveitis and explore the pathophysiology and treatment of this condition. This study is a case report and review of the literature.
A 15-year-old boy with intermediate uveitis - suppressed for the preceding year on immunosuppressive therapy and low-dose corticosteroids - and chronic disc swelling presented with unilateral metamorphopsia, peripapillary subretinal hemorrhage, and subretinal fluid. Fluorescein angiogram confirmed the presence of an active choroidal neovascular membrane. Treatment with intravitreal bevacizumab 1.25 mg every 4 weeks for 4 months resulted in resolution of subretinal fluid, subretinal hemorrhage, and regression of the CNV. The patient's intermediate uveitis remained inactive throughout this time.
Review of the existing literature and pathophysiologic consideration suggests that chronic disc edema may be a risk factor for this condition. Peripapillary CNV in the context of intermediate uveitis appears to respond well to VEGF-inhibitor therapy.
Choroidal neovascularization (CNV) occurs rarely in the context of intermediate uveitis . Only three such cases have previously been reported in the English literature, two of which presented in a peripapillary location [1, 2]. In the Systemic Immunosuppressive Therapy for Eye Diseases (SITE) Cohort Study, representing the experience of five US tertiary uveitis centers including ours, 0/1,978 patients with intermediate uveitis presented with peripapillary CNV (upper limit of a one-sided 97.5% confidence interval = 0.19%). Here, we report a case of peripapillary CNV in a patient with intermediate uveitis and explore the pathophysiology and outcome of this condition. The project was conducted in accordance with the principles of the Declaration of Helsinki, with the approval of the governing Institutional Review Board of the University of Pennsylvania.
After completion of the SITE Cohort Study at our center, a 15-year-old male presented to our institution with blurry vision in the inferotemporal quadrant of the left eye for 1 day, which upon further questioning represented metamorphopsia. The patient denied redness, eye pain, light sensitivity, or floaters. The patient had longstanding intermediate uveitis and chronic disc swelling, which we observed to be suppressed for the past year. At the time of presentation with metamorphopsia, the patient was taking mycophenolate mofetil 1 g twice daily, methotrexate 25 mg once weekly, and folic acid 1 mg daily. He was otherwise healthy, and past medical history was unremarkable. Previous laboratory workup for conditions associated with intermediate uveitis was negative.
Throughout this time, the patient's intermediate uveitis remained inactive. He was maintained on mycophenolate mofetil 1 g twice daily and methotrexate 25 mg once weekly. He was followed-up at our institution regularly over the next 3 years and did well. At last follow-up, the uveitis was inactive; no recurrence of CNV or disc swelling was noted throughout this period. His complaints of metamorphopsia gradually subsided, but he is still aware of metamorphopsia when he covers the right eye corresponding to the still-persistent traction lines in the nasal macula. It remains unclear whether the etiology of the disc swelling was from slowly resolving inflammatory disc edema, corticosteroid-induced intracranial hypertension, or both.
Literature summary of choroidal neovascularization in intermediate uveitis
Location of CNV
Active intraocular inflammation at the time of CNV
Arkfeld and Brockhurst 
Peripapillary (temporal to disc)
Argon green laser photocoagulation
Chronic disc swelling present prior to CNV
Garcia et al. 
Peripapillary-(temporal to disc)
Intravitreal bevacizumab × 1
Disc swelling present
Garcia et al. 
Chronic cystoid macular edema present prior to CNV
Peripapillary (superior and temporal to disc)
Intravitreal bevacizumab × 4
Chronic disc swelling present prior to CNV
Histopathologic studies have provided insight into the potential mechanisms in the development of peripapillary CNV . Sarks provided clinicopathologic correlation of 21 eyes with peripapillary CNV from AMD . Based on histopathologic evidence, Sarks hypothesized that peripapillary CNV originates either from the choroidal vessels passing around the termination of Bruch's membrane or from the choroidal vessels passing through defects in Bruch's membrane. In the above reported cases of peripapillary CNV in intermediate uveitis, it is interesting to note that chronic disc edema was present prior to the onset of all cases. Arkfeld and Brockhurst hypothesized that chronic disc swelling may increase the potential space between Bruch's membrane and swollen disc tissue facilitating ingrowth of choroidal vessels around the termination of Bruch's membrane . Alternatively, chronic disc swelling may result in the deformation of the peripapillary Bruch's membrane leading to breaks in Bruch's membrane facilitating ingrowth of the choroidal neovascular tissue under the RPE . Peripapillary CNV has also been observed in conditions causing chronic disc swelling such as idiopathic intracranial hypertension and hydrocephalus [5–8].
Peripapillary CNV is characterized clinically by the presence of a choroidal neovascular membrane adjacent to the disc producing subretinal hemorrhage, fluid, and/or exudate . OCT characteristics suggestive of CNV include the presence of subretinal fluid, subretinal hemorrhage, subretinal hyperreflective lesion, and intraretinal fluid. On fluorescein angiogram, well-defined CNV appears as a lacy network of capillary plexuses with leakage as the angiogram progresses . Occult CNV can appear as an area of stippled hyperfluorescence on angiogram. The choroidal neovascular membrane may be obscured by hemorrhage, pigment hyperplasia, fibrous tissue, or serous pigment epithelial detachment .
Peripapillary CNV has certain unique features compared to its macular counterpart. First, peripapillary CNV is associated not just with diseases affecting chorioretinal tissue adjacent to the disc but also with diseases affecting the optic nerve head. For example, peripapillary CNV can be seen in optic disc drusen, congenital disc anomalies, tilted disc, and disc swelling . Second, peripapillary CNV may develop from the breakthrough of abnormal choroidal blood vessels through Bruch's membrane in addition to growth of vessels around the termination of Bruch's membrane [2–4]. Third, the occurrence of clinical symptoms prior to the extension of the lesion into the fovea may allow detection and treatment of these lesions with potentially more favorable visual outcomes compared to their foveal counterparts .
Several treatment options exist for peripapillary CNV in uveitis including vascular endothelial growth factor inhibitors, argon laser photocoagulation, and photodynamic therapy [10–13]. In the above cases, all patients underwent treatment with either argon laser photocoagulation or intravitreal bevacizumab (as used in our case) and did well with significant improvements in vision and CNV regression. For lesions adjacent to vital structures such as the optic disc, therapy with bevacizumab injection likely is safer than laser photocoagulation or photodynamic therapy and is reasonably cost-effective.
In conclusion, patients with intermediate uveitis and chronic disc swelling may be at risk for peripapillary CNV. Control of inflammation without the use of corticosteroids likely will improve disc swelling in most cases, even though resolution of disc swelling may be delayed in some instances, as in our case. Corticosteroid-induced or idiopathic intracranial hypertension should be suspected in cases with ongoing disc swelling without active inflammation. Chronic disc swelling should be resolved if possible to avoid complications. CNV has been reported to develop during times of quiescence or active inflammation [1, 2]. Management with a vascular endothelial growth factor inhibitor likely is the treatment of choice, along with control of inflammation and control of any associated factors that may be present such as intracranial hypertension . Based on the limited number of observations available, the prognosis of this condition with appropriate treatment appears favorable.
This study was supported primarily by a generous contribution to the Scheie Eye Institute by the Klein family. The SITE Cohort Study was supported by the National Eye Institute Grant EY014943 (JHK). Additional support was provided by the Research to Prevent Blindness and the Paul and Evanina Mackall Foundation.
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