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Navigating the Challenges of Photodynamic Therapy: Understanding and Managing Acute Exudative Maculopathy

  • Overview of Photodynamic Therapy (PDT):

    • PDT is a treatment for choroidal pathologies, involving intravenous infusion of a photosensitizing agent (e.g., Verteporfin) followed by targeted light exposure at 689 nm.

    • Standard full-fluence PDT protocol (TAP trial): 83 seconds of 689 nm light at 50 J/cm², 600 mW/cm², 5 minutes after a 10-minute infusion of 6 mg/m² Verteporfin.

    • Half-fluence PDT (25 J/cm²): Preferred in central serous chorioretinopathy (CSCR) due to better vision retention and lower risk of macular ischemia.

    • Applications include CSCR, polypoidal choroidal vasculopathy (PCV), neovascular age-related macular degeneration (nAMD), choroidal hemangioma, retinal capillary hemangioma, and choroidal neovascular membrane (CNVM) related to pathologic myopia.

  • PDT-Induced Acute Exudative Maculopathy (PAEM):

    • Definition: Transient increase in subretinal fluid within days post-PDT, leading to acute vision decrease and exudative retinal detachment.

    • Etiology: Excessive PDT mechanism causing choriocapillaris vessel obliteration, inflammation, and increased vascular permeability via cytokines (e.g., VEGF) and reactive oxygen species. Retinal pigment epithelium (RPE) pump dysfunction may contribute.

    • Prevalence: Occurs in 1.4–30.4% of PDT-treated patients, highest in CSCR (30.4%), followed by PCV (8.45%) and nAMD (6.67%).

 

    • Risk Factors (Manayath et al, 2020):

      • Age >65 years

      • PCV

      • Spot size >3.5 mm

      • Pre-treatment best corrected visual acuity (BCVA) ≥20/40

      • First-time PDT

      • Reduced-fluence PDT

 

    • Note: Full-fluence PDT may have equal or higher PAEM risk, but data is limited due to its rarity compared to reduced-fluence PDT.

    • Fernandez-Vigo et al (2022): No statistically significant risk factors in CSCR patients treated with half-fluence PDT; PAEM associated with worse baseline VA and flow voids on OCT-A.

  • Diagnosis of PAEM:

    • No standardized criteria: Diagnosis relies on optical coherence tomography (OCT) showing increased central macular thickness (CMT).

    • Manayath et al: Mean CMT increase of 253 µm at 2.9 days post-PDT.

    • Fernandez-Vigo et al: Defined PAEM as CMT increase ≥50 µm at 3 days post-PDT in CSCR, with decreasing incidence at higher thresholds (100 µm, 200 µm).

 

    • 25% of PAEM cases have CNVM (vs. 8.4% in controls), per Fernandez-Vigo et al.

 

  • Prognosis:

    • Vision Loss Severity: Ranges from mild (20/30) to severe (no light perception).

    • Resolution Timeline: Typically 2–6 weeks, with most cases recovering to near pre-PDT BCVA (≥20/60).

    • Exception: One case with retinal capillary hemangioma required vitrectomy, taking 1 year to recover from no light perception to 20/500.

  • Management Strategies:

    • Observation: Effective, especially in CSCR, with resolution in 1–4 weeks due to vascular recanalization (evidenced by OCT-A and histopathologic analysis).

    • Corticosteroids:

      • Systemic (e.g., oral prednisone, IV methylprednisolone): Targets choroidal inflammation but risks disease exacerbation in pachychoroid conditions and systemic side effects.

      • Periocular (e.g., sub-Tenon triamcinolone acetonide, STTA): FDA-approved suprachoroidal triamcinolone may improve access to pathology site with fewer side effects.

      • Topical (e.g., difluprednate): Effective in low-fluence PDT cases, mitigates systemic risks.

    • Anti-VEGF Injections (e.g., bevacizumab, ranibizumab, aflibercept): Address elevated VEGF from PDT-induced ischemia; may reduce resolution time but carry risks in patients prone to arteriothrombotic events.

    • Combination Therapies: Examples include intravitreal bevacizumab with triamcinolone or dexamethasone for PCV and CSCR.

    • No randomized controlled trials: Limited data preclude firm conclusions on treatment efficacy vs. observation.

  • Complications of PDT (beyond PAEM):

    • Photosensitivity (3–5 days)

    • Nausea, dry eye, flank pain, joint pain

    • Vision-threatening complications: Choroidal ischemia, RPE tear, RPE atrophy, secondary CNVM, subretinal hemorrhage

  • Clinical Recommendations:

    • Monitor PAEM with serial OCT and examinations; OCT-A if available.

    • Professional societies should develop standardized diagnostic criteria and management guidelines for PAEM.

    • Further research needed on PAEM incidence across conditions and treatment efficacy vs. observation.

  • Key Studies:

    • TAP Trial (1999): Established PDT efficacy for nAMD with classic CNVM.

    • EVEREST I and II: PDT + PRN ranibizumab superior to ranibizumab alone for PCV in polyp regression and visual acuity.

    • PLANET Study: No clear benefit of PDT as rescue therapy in PCV treated with aflibercept.

    • Manayath et al (2020): Identified PAEM risk factors and treatment outcomes in a large cohort.

    • Fernandez-Vigo et al (2022): No significant risk factors in CSCR; PAEM linked to worse baseline VA and CNVM.