Treatment of Macular Hemorrhage in Pseudoxanthoma Elasticum
Intravitreal anti-VEGF therapy is the treatment of choice for macular hemorrhage in PXE patients, as it effectively treats the underlying choroidal neovascularization (CNV) that causes these hemorrhages and can maintain or improve visual acuity, particularly when initiated before central vision is affected. 1, 2
Immediate Management Approach
Perform comprehensive retinal imaging including optical coherence tomography (OCT) to assess for intra/subretinal fluid and fluorescein angiography combined with indocyanine green angiography (FFA + ICGA) to confirm CNV activity, which is the primary cause of macular hemorrhage in PXE 3, 2
Initiate anti-VEGF treatment promptly before the hemorrhage causes irreversible central vision loss, as a BCVA drop at exudation onset is a significant risk factor for worse long-term visual outcomes 2
Anti-VEGF Treatment Protocol
Begin with intravitreal anti-VEGF injections using ranibizumab, bevacizumab, aflibercept, or conbercept, as all have demonstrated efficacy in treating CNV secondary to angioid streaks in PXE 1, 4, 3
Expect approximately 5-7 injections in the first year of treatment, with ongoing treatment needs throughout the observation period, as PXE patients typically require intensive long-term management 2
Use an as-needed (PRN) treatment regimen guided by OCT evidence of intra/subretinal fluid and funduscopic evidence of hemorrhage, adjusting treatment intervals based on individual CNV activity 1, 2
Consider maintenance therapy every 2 months in selected patients with persistent disease activity, though PRN remains the most commonly used strategy 1
Prognostic Factors and Treatment Timing
Better baseline visual acuity predicts better final outcomes (P < .001, R² = 0.318), emphasizing the importance of early detection and treatment 2
Absence of BCVA drop before treatment initiation is associated with significantly better visual outcomes (P = 0.035, R² = 0.339), making prompt treatment before central retinal involvement critical 2
Early-stage disease responds best to anti-VEGF therapy, with visual acuity maintained or improved over prolonged periods even with relatively few injections, while late-stage disease with widespread atrophic changes has a more guarded prognosis 1
Fellow Eye Monitoring
Examine the fellow eye carefully and frequently, as the median time to requiring treatment in the second eye is only 16.8 months after first eye treatment, with a median interval of 9.6 months between bilateral treatments 2
Monitor for angioid streaks, peau d'orange changes, and early CNV development in the fellow eye, as most PXE patients eventually require bilateral treatment 2
Critical Pitfalls to Avoid
Do not delay treatment waiting for hemorrhage to clear spontaneously, as this allows progressive damage to the central retina and significantly worsens visual prognosis 2
Avoid using laser photocoagulation or photodynamic therapy as first-line treatment, as anti-VEGF therapy has superseded these modalities and shows superior outcomes for CNV in PXE 5, 1
Counsel patients about the off-label nature of anti-VEGF treatment for this indication and discuss possible (though unproven) increased cardiovascular/thromboembolic risks, particularly relevant given PXE's systemic vascular involvement 1
Recognize that PXE patients require treatment at relatively young ages (median 52.8 years) and need intensive long-term follow-up, making patient education about treatment commitment essential 2
Multisystem Evaluation
Refer newly diagnosed PXE patients to cardiology, gastroenterology, and genetics for comprehensive evaluation and counseling, as PXE affects multiple organ systems including cardiovascular and gastrointestinal systems 4
Confirm diagnosis with skin biopsy showing calcium deposition and fragmented, clumped elastic fibers in the deep reticular dermis when characteristic "chicken skin" changes are present on the neck 4, 3