ABSTRACT
OBJECTIVE: To evaluate the early effects of triamcinolone acetonide (TA) on inflammation, proliferation, and vascular endothelial growth factor (VEGF) in human choroidal neovascularization (CNV). METHODS: Retrospective review of an interventional case series of 29 patients who underwent macular translocation. Fourteen CNV membranes without previous therapy (control CNV group) and 4 CNV membranes excised 3 days after photodynamic therapy (PDT CNV group) comprised the control groups. Eleven patients were treated with intravitreal TA (TA CNV group; n = 5) or PDT and TA combined (PDT+TA CNV group; n = 6) 3 to 9 days preoperatively. The CNV membranes were stained for cytokeratin 18, CD34, VEGF, intercellular adhesion molecule-1 (ICAM-1), E-selectin, CD68, CD45, Ki-67, and Thy-1. RESULTS: Treatment with TA and PDT+TA resulted in increased immunostaining of ICAM-1 in endothelial cells and the stroma and a higher percentage of Thy-1 expression than controls. The density of macrophages was significantly increased in PDT+TA CNV membranes. Leukocyte density and proliferative activity were lower in TA and PDT+TA CNV membranes. The total VEGF score was significantly increased in TA and PDT+TA CNV membranes compared with the control CNV membranes. Evidence of VEGF in the retinal pigment epithelium of PDT+TA CNV membranes was stronger than in control CNV membranes. CONCLUSIONS: Triamcinolone acetonide has no inhibitory effect on macrophage infiltration or ICAM-1, Thy-1, or VEGF expression in CNV membranes in the early term. The clinical benefits of TA are probably not based on pure antiinflammatory or VEGF-suppressing mechanisms.
Subject(s)
Anti-Inflammatory Agents/therapeutic use , Choroidal Neovascularization/drug therapy , Leukocytes/pathology , Lymphocyte Activation , Macrophages/pathology , Triamcinolone Acetonide/therapeutic use , Vascular Endothelial Growth Factor A/metabolism , Aged , Aged, 80 and over , Antigens, CD/metabolism , Antigens, Differentiation, Myelomonocytic/metabolism , Choroidal Neovascularization/metabolism , Choroidal Neovascularization/pathology , Choroidal Neovascularization/surgery , Combined Modality Therapy , E-Selectin/metabolism , Female , Humans , Immunoenzyme Techniques , Inflammation/drug therapy , Inflammation/metabolism , Injections , Intercellular Adhesion Molecule-1/metabolism , Laser Coagulation , Leukocyte Common Antigens/metabolism , Leukocyte Count , Macular Degeneration/surgery , Male , Middle Aged , Photochemotherapy , Retina/transplantation , Retrospective Studies , Thy-1 Antigens/metabolism , Vitreous BodyABSTRACT
PURPOSE: To evaluate the closure rate after macular hole surgery with air tamponade and face-down positioning whose duration is based on postoperative optical coherence tomography (OCT). METHODS: In a prospective study, data were gathered on 33 eyes of 33 consecutive patients undergoing macular hole surgery. Postoperatively, OCT images were obtained in a face-down position to minimize the interfering reflections created by the air bubble. The face-down positioning was ended as soon the OCT revealed closure of the hole. RESULTS: Opacity of the media in 8/33 eyes 24 hours postoperatively precluded OCT. In 18/33 eyes (54.5%), the hole was closed on OCT 24 hours postoperatively and in 25/33 (75.7%), 48 hours postoperatively. In 4/33 eyes (12.1%), the hole was judged to be open on OCT 24 hours postoperatively. Despite continued face-down positioning, the hole had closed on the third day postoperatively in only one of these four eyes. In two of the remaining three eyes, the macular hole could be closed by a second surgery which was performed 5 to 6 days after the first vitrectomy. Using OCT monitoring, more than half (54%) of our patients could quit the face-down position after 24 hours, 21% after 48 hours, and 24% after 3 days. CONCLUSION: Vitrectomy and air tamponade combined with 1- to 3-day face-down positioning produced an excellent rate of macular hole closure. Already on the first and second day postoperatively OCT on patients in a prone position enabled the monitoring of the progress of the macular hole closure through the air bubble. This method allows effective adjustment of the duration of face-down positioning based on OCT findings.
Subject(s)
Ophthalmologic Surgical Procedures/methods , Prone Position , Retinal Perforations/diagnosis , Retinal Perforations/surgery , Tomography, Optical Coherence , Aged , Air , Equipment Design , Humans , Middle Aged , Postoperative Period , Prospective Studies , Retinal Perforations/physiopathology , Time Factors , Tomography, Optical Coherence/instrumentation , Treatment Outcome , Visual AcuityABSTRACT
AIM: To evaluate expression of proangiogenic matrix metalloproteinases (MMP) 2 and 9 at distinct intervals after verteporfin photodynamic therapy (PDT) in human choroidal neovascular membranes (CNV) secondary to age-related macular degeneration (AMD). METHODS: Retrospective review of an interventional case series of 49 patients who underwent removal of CNV. Twenty-six patients were treated with PDT 3 to 383 days prior to surgery. Twenty-three CNV without previous treatment were used as controls. CNV were stained for CD34, cytokeratin 18, endostatin, MMP-2 and MMP-9 by immunohistochemistry. RESULTS: CNV without previous therapy disclosed MMP-2, MMP-9 in RPE-Bruch's membrane, vessels and stroma in different intensities. Three days after PDT, MMP-9 expression was significantly weaker in stroma (p = 0.0019). Endostatin was significantly reduced in vessels (p<0.001). At longer post-PDT intervals, a significant increase of MMP-9 in stroma (p = 0.037) and of endostatin in RPE-Bruch's membrane (p = 0.02), vessels (p = 0.005) and stroma (p<0.001) were disclosed. No significant changes in MMP-2 expression were detected. CONCLUSIONS: PDT induced an early, temporary decrease in MMP-9 and endostatin expression. At longer intervals, MMP-9 increase is possibly associated with the angiogenic process responsible for recurrence after PDT. MMP-9, however, acts as a double-edged sword by concomitant induction of endostatin, an endogenous inhibitor of angiogenesis.
Subject(s)
Choroidal Neovascularization/enzymology , Matrix Metalloproteinase 2/metabolism , Matrix Metalloproteinase 9/metabolism , Photochemotherapy/methods , Aged , Aged, 80 and over , Biomarkers/metabolism , Choroidal Neovascularization/etiology , Choroidal Neovascularization/surgery , Endostatins/metabolism , Female , Humans , Immunoenzyme Techniques , Macular Degeneration/complications , Macular Degeneration/surgery , Male , Middle Aged , Photosensitizing Agents/therapeutic use , Porphyrins/therapeutic use , Retrospective Studies , VerteporfinABSTRACT
AIM: To evaluate the effect of verteporfin photodynamic therapy (PDT) on endostatin with regard to expression of vascular endothelial growth factor (VEGF) in human choroidal neovascular membranes (CNVs) secondary to age-related macular degeneration. METHODS: A retrospective review of an interventional case series of 68 patients who underwent removal of CNV. 29 patients were treated with PDT 3-655 days before surgery. 39 CNVs without previous treatment were used as controls. CNVs were stained for CD34, CD105, Ki-67, cytokeratin 18, endostatin, E-selectin and VEGF. "Predominance score of VEGF over endostatin" (mean) was defined as the difference between VEGF and endostatin staining scores. RESULTS: In four CNVs treated by PDT 3 days previously, PS was significantly higher in the retinal pigment epithelium (mean = 2.5, p = 0.006) and stroma (mean = 2, p = 0.015) than in the control group (mean = 0). At longer post-PDT intervals, PS was significantly decreased in the retinal pigment epithelium (mean = 0, p = 0.019) and stroma (mean = 0, p = 0.015). Proliferative activity was high (p = 0.023), but mostly related to inflammatory cells. PDT did not influence E-selectin expression significantly. CONCLUSIONS: VEGF predominance over endostatin early after PDT might contribute to enhanced angiogenic activity associated with recurrences. Strategies upregulating or replacing endostatin early after PDT might increase the effectiveness of PDT.
