Case presentation

A 53-year-old Chinese woman with PXE and angioid streaks was referred in May 2012 because of noticing visual loss in his left eye (LE) of 2 month’s duration, and the occurrence of metamorphopsia and central scotoma. Her right eye (RE) was unaffected. The patient reported the onset of yellowish asymptomatic micropapules in the cervical region 10 years ago (Figure 1A,B), which later progressed to the axillae and cubital fossae. In her personal records, a history of arterial hypertension or diabetes mellitus was not noticed. The patient denied similar cases in her family but her daughter, who reported the onset of yellowish asymptomatic micropapules in 2 years ago, and the presence of bilateral angioid streaks confirmed by ophthalmoscopy and fundus photography (Figure 1C,D). They two were diagnosed with angioid streaks associated with PXE, which was confirmed by skin biopsy.

Table 1 Characteristics and clinical data of CNV secondary to angioid streaks in PXE treated with anti-VEGF

A systematic review of the cases reported in the literature was conducted to examine the safety and effectiveness of intravitreal anti-VEGF treatment for CNV associated with PXE. We searched Cochrane Library, PubMed, OVID, and UpToDate databases (from inception to July 2015) using combinations of search terms including pseudoxanthoma elasticum or Grönblad-Strandberg syndrome and VEGF or CNV. Electronic searches were supplemented by perusal of the references of the retrieved papers. All potentially eligible studies and their references were carefully scanned to identify other eligible studies.

Discussion

Previous methods of treatment for CNV in patients with PXE such as thermal photocoagulation and verteporfin PDT had poor outcomes ^(19-22). This presumably resulted from the treatment itself creating tissue injury and high recurrence rates after these procedures. This case report demonstrates that intravitreal bevacizumab is effective and safe treatment options for CNV secondary to PXE. The presented case report supports and confirms so far published evidence for the effectiveness of bevacizumab in CNVs secondary to PXE.

In patients with PXE who have an increased cardiovascular risk profile, possible complications of intravitreal treatment with bevacizumab need to be considered. Patients need to be aware of the possibility of systemic side effects such as myocardial infarction or a deterioration of their cardiovascular; although at present no definite proof has been documented of this higher risk in patients with or without PXE treated with intravitreal anti-VEGF. No drug- or injection-related complications were noted in these literatures. No patients with PXE experienced increased intraocular pressure, inflammation, endophthalmitis, retinal breaks, retinal detachment, or ocular or systemic occlusive events (including myocardial infarction and cerebral ischemia).

The risk of recurrent exudation of CNV associated with angioid streaks in PXE and likely need for repeated injections is obvious ⁽¹²⁾. Most eyes required repeated injections to achieve CNV quiescence and visual stabilization. Despite the higher recurrence rate in the eyes that received intravitreal anti-VEGF as needed for recurrence, both maintenance and PRN treatment regimens seemed capable of stabilizing or improving final VA outcomes in most patients. However, the ideal timetable and criteria for injections have yet to be determined. Although there seem to be arguments to treat selected patients with a maintenance treatment of intravitreal injections once a month, an as-needed regimen is the most used strategy. Further prospective, randomized controlled clinical trials with defined treatment protocols would be necessary to elucidate the ideal timing and criteria for intravitreal antiVEGF administration for managing CNV from PXErelated angioid streaks. Specifically, studies with close regular follow-up comparing the efficacy of a maintenance regimen versus an as needed regimen are required.

A limitation of these case series is the retrospective study design. Ideally, effectiveness of bevacizumab in CNVs because of PXE should be assessed in a randomized controlled clinical trial. However, because withholding treatment for CNVs because of PXE is very problematic, clinical trials are most likely to be implemented uncontrolled. PXE is a rare disease, and therefore, largescale trials appear unrealistic. Continued experience with intravitreal bevacizumab or ranibizumab in this population will help establish long-term efficacy and better define optimal dosing strategies.

Overall, based on the evidence available, intravitreal treatment with anti-VEGF seems to be the best choice at present to treat patients with CNV secondary to angioid streaks of PXE. Further studies and larger case series are needed to clarify the role of anti-VEGF therapy in managing CNV secondary to PXE.