Macular Degeneration: Zografos L

Sickenberg M, Schmidt-Erfurth U, Miller JW, Pournaras CJ, Zografos L, Piguet B, Donati G, Laqua H, Barbazetto I, Gragoudas ES, Lane AM, Birngruber R, van den Bergh H, Strong HA, Manjuris U, Gray T, Fsadni M, Bressler NM. · Hopital Ophtalmique Jules Gonin, Lausanne, Switzerland. · Arch Ophthalmol. · Pubmed #10721954 No free full text.

Abstract: OBJECTIVE: To evaluate short-term safety and the effects on visual acuity and fluorescein angiography of single or multiple sessions of photodynamic therapy with verteporfin for choroidal neovascularization (CNV) not related to age-related macular degeneration (AMD), including pathologic myopia, the ocular histoplasmosis syndrome, angioid streaks, and idiopathic causes. DESIGN: A nonrandomized, multicenter, open-label, dose-escalation phase 1 and 2 clinical trial. SETTING: Four ophthalmic centers in Europe and North America providing retinal care. PARTICIPANTS: Thirteen patients with subfoveal CNV due to pathologic myopia, the ocular histoplasmosis syndrome, angioid streaks, or idiopathic causes. METHODS: Standardized protocol refraction, visual acuity testing, ophthalmic examinations, color photographs, and fluorescein angiograms were used to evaluate the results of photodynamic therapy treatments with verteporfin. Follow-up ranged from 12 weeks for patients who were treated once to 43 weeks for patients who were treated up to 4 times. RESULTS: Verteporfin therapy was well tolerated in patients with CNV not related to AMD. No deterioration in visual acuity was observed; most patients gained at least 1 line of vision. Reduction in the size of leakage area from classic CNV was noted in all patients as early as 1 week after verteporfin therapy, with complete absence of leakage from classic CNV in almost half of the patients. Improvement in visual acuity after verteporfin therapy was greatest (+6, +8, and +9 lines) in 3 patients with relatively poor initial visual acuity (between 20/200 and 20/800). Up to 4 treatments were found to have short-term safety even with retreatment intervals as short as 4 weeks. CONCLUSIONS: Treatment of CNV not related to AMD with verteporfin therapy achieves short-term cessation of fluorescein leakage from CNV in a small number of patients without loss of vision. Further randomized clinical trials including a larger number of patients are under way to confirm whether verteporfin therapy is beneficial for subfoveal CNV not related to AMD.

Schmidt-Erfurth U, Miller JW, Sickenberg M, Laqua H, Barbazetto I, Gragoudas ES, Zografos L, Piguet B, Pournaras CJ, Donati G, Lane AM, Birngruber R, van den Berg H, Strong HA, Manjuris U, Gray T, Fsadni M, Bressler NM. · Retina Department, University Eye Hospital, Lübeck, Germany. · Arch Ophthalmol. · Pubmed #10496389 No free full text.

Abstract: OBJECTIVES: To evaluate safety and short-term visual acuity and fluorescein angiographic effects of photodynamic therapy (PDT) after retreatments with verteporfin for choroidal neovascularization (CNV) in age-related macular degeneration (AMD) that demonstrated fluorescein leakage after at least 1 course of PDT. DESIGN: Nonrandomized, multicenter, open-label phase 1 and 2 clinical trial using 2 different retreatment dosage regimens. SETTING: Four ophthalmic centers in Europe and North America providing retinal care. METHODS: Standardized protocol refraction, visual acuity testing, ophthalmic examinations, color photographs, and fluorescein angiograms were used to evaluate the results of multiple PDT treatments. Two regimens (regimens 2 and 4) for treatment and retreatment were chosen from 5 used in a single-treatment study. Both regimens used a verteporfin dose of 6 mg/m2 infused for 10 minutes. However, regimen 2 used a light dose of 100 J/cm2 applied 20 minutes after the start of the verteporfin infusion, whereas regimen 4 used a light dose of 50, 75, or 100 J/cm2 applied 15 minutes after infusion commenced. Posttreatment evaluations were planned in 31 participants up to 3 months after up to 2 retreatments given at 2- or 4-week intervals after initial PDT treatment. Similar posttreatment evaluations were planned after retreatments in 5 additional participants who were reenrolled some time more than 12 weeks after an initial PDT treatment. RESULTS: The average visual acuity change for the 31 participants who had retreatment within 2 to 4 weeks after the initial treatment and a follow-up examination 16 to 20 weeks after the initial treatment was 0.2 lines (range, -4 to 4 lines) in regimen 2 and -1.0 line (range, -5 to 3 lines) in regimen 4. Similar outcomes were noted in the 5 reenrolled participants. Cessation of fluorescein leakage from classic CNV for at least 1 to 4 weeks could be achieved without loss of visual acuity after at least 2 treatments in 2 (6.5%) of 31 patients. Similar to single-treatment effects, the disappearance of leakage was documented regularly at 1 week after each retreatment. Fluorescein leakage reappeared by 4 to 12 weeks after a retreatment in almost all cases. However, compared with baseline, leakage activity appeared to be reduced after multiple PDT courses. For the 31 patients who had follow-up for 3 months after the last retreatment and had received retreatment 2 to 4 weeks after the initial treatment, progression of CNV beyond the area identified before the retreatment was noted in 10 (48%) of the 21 eyes with classic CNV in regimen 2 and 9 (90%) of 10 eyes in regimen 4. The rate and severity of ocular or systemic adverse events were not increased by multiple applications. CONCLUSIONS: Multiple applications of PDT with verteporfin achieve repetitive, short-term cessation of fluorescein leakage from CNV secondary to AMD, without loss of visual acuity. This strategy can be used in randomized clinical trials investigating the efficacy of verteporfin in PDT for recurrent fluorescein dye leakage from persistent or recurrent CNV, following an initial or subsequent PDT treatment, with maintenance of visual acuity. Retreatments may achieve progressive cessation of leakage and prevent further growth of CNV and subsequent visual loss.

Miller JW, Schmidt-Erfurth U, Sickenberg M, Pournaras CJ, Laqua H, Barbazetto I, Zografos L, Piguet B, Donati G, Lane AM, Birngruber R, van den Berg H, Strong A, Manjuris U, Gray T, Fsadni M, Bressler NM, Gragoudas ES. · Retina Service, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, USA. · Arch Ophthalmol. · Pubmed #10496388 No free full text.

Abstract: OBJECTIVE: To evaluate the safety and short-term visual and fluorescein angiographic effects of a single photodynamic therapy treatment with verteporfin with the use of different dosage regimens in patients with choroidal neovascularization (CNV) from age-related macular degeneration. DESIGN: Nonrandomized, multicenter, open-label, clinical trial using 5 dosage regimens. SETTING: Four ophthalmic centers in North America and Europe providing retinal care. PARTICIPANTS: Patients with subfoveal CNV caused by age-related macular degeneration. METHODS: Standardized protocol refraction, visual acuity testing, ophthalmic examination, color photographs, and fluorescein angiograms were used to evaluate the effects of a single treatment of photodynamic therapy with verteporfin. Follow-up was planned through 3 months in 97 patients and for less than 3 months in 31 other patients. RESULTS: The mean visual acuity change (and range of change) from baseline at the follow-up examination at week 12 after a single treatment with regimens 1 through 5 was -0.2 (-3 to +2), -0.9 (-9 to +5), -1.6 (-9 to +2), +0.4 (-8 to +7), and +0.1 (-8 to +9) lines, respectively. Only the highest light dose (150 J/cm2) in regimens 2 and 3, which produced angiographic nonperfusion of neurosensory retinal vessels, caused marked vision loss. Some cessation of fluorescein leakage from CNV was achieved without loss of vision when the light dose used was less than 150 J/cm2. Systemic adverse events were rare. Cessation of fluorescein leakage from CNV was noted in all regimens by 1 week after photodynamic therapy. Fluorescein leakage from at least a portion of the CNV reappeared by 4 to 12 weeks after treatment in almost all cases. Progression of classic CNV beyond the area of CNV identified before treatment was noted in 42 (51%) of the 83 eyes with classic CNV followed up for 3 months after a single treatment. Eyes in which the area of any CNV leakage at 12 weeks was less than at baseline had a significantly better visual acuity outcome (+0.8 line) than eyes in which CNV leakage progressed (-0.8 line). CONCLUSIONS: Photodynamic therapy with verteporfin achieved short-term cessation of fluorescein leakage from CNV without loss of vision or growth of classic CNV in some patients with age-related macular degeneration. Except for nonperfusion of neurosensory retinal vessels at a light dose of 150 J/cm2, no other adverse events were of concern. Randomized clinical trials to investigate whether this new modality can preserve vision in patients with CNV secondary to age-related macular degeneration are justified.

Mantel I, Zografos L, Ambresin A. · Ophthalmology Department, University of Lausanne, Lausanne, Switzerland. · Ophthalmologica. · Pubmed #18617755 No free full text.

Abstract: BACKGROUND: In large randomized multicenter trials, ranibizumab has shown its therapeutic efficacy for exudative age-related macular degeneration (AMD). The aim of this paper is to report the real-life clinical experience with this treatment for occult and minimally classic membranes without pigment epithelium detachment. METHODS: We conducted a retrospective chart review of 37 patients with occult and minimally classic neovascular membranes in AMD, without pigment epithelium detachment. RESULTS: The mean visual improvement of 2 lines at 3, 6 and 9 months corresponds well with the results of the large trials. A mean number of 5 reinjections was reached by month 8. It may potentially exceed the mean 5.5 injections of the PrONTO study (prospective optical coherence tomography imaging of patients with neovascular AMD treated with intraocular ranibizumab). At months 6-8 recurrence was frequently observed. CONCLUSION: The early experience of ranibizumab in clinical practice brings similarly good results as the large-scale trials. However, interrupting the treatment too early may be a disadvantage.

Mantel I, Ambresin A, Zografos L. · University Eye Clinic, Hôpital Jules Gonin, Lausanne, Switzerland. · Eur J Ophthalmol. · Pubmed #17061221 No free full text.

Abstract: PURPOSE: Retinal angiomatous proliferation (RAP) is a particularly aggressive form of exudative age-related macular degeneration. Response to laser photocoagulation or to photodynamic therapy (PDT) alone is often disappointing. The purpose of this study was to determine whether intravitreal triamcinolone acetate (TA) injections followed by PDT in eyes with early stage RAP may be effective. METHODS: Prospective uncontrolled study, enrolling 11 patients (11 eyes) with stage 2 RAP, treated with intravitreal TA injection followed by PDT. Patients with large pigment epithelium detachment, RAP stage 3, or pre-existing glaucoma and known steroid responders were excluded. All patients underwent a complete ophthalmic examination including fluorescein and indocyanine green (ICG) angiography and optical coherence tomography (OCT-3) at baseline and at 1, 3, 6, and 12 months. Informed consent was obtained from all patients. RESULTS: Mean follow-up was 14.9 months (range 6 C21 months). Mean age was 82 years. In four patients a small pigment epithelium detachment was found on tomography. Initial visual acuity (VA) ranged from 0.1 to 0.6 on the Snellen scale. After calculating the logarithmic values the authors found an initial mean VA of logMAR 0.61, which improved by 1.5, 0.9, and 0.9 log lines after 3, 6, and 12 months, respectively. Although the VA gain from baseline tended to decrease with time, only 2 patients (18%) had an actual loss of acuity>or=3 lines). Retreatment was required in 5 eyes. CONCLUSIONS: In this prospective pilot study examining the use of intravitreal TA followed by PDT with verteporfin in eyes with stage 2 RAP, without a large pigment epithelium detachment, the authors found a potential benefit in terms of stabilization or even improvement of vision.

Guex-Crosier Y, Zografos L. · Hôpital ophtalmique Jules Gonin, Université de Lausanne, 15, avenue de France, 1004 Lausanne. · Rev Med Suisse. · Pubmed #15773215 No free full text.

Abstract: Anti-TNF-alpha (infliximab and etanercept) are potent, selective inhibitors of the inflammatory cascade. They have been widely used in the therapy of rheumatoid arthritis, Crohn's disease and psoriasis. Their efficacy in ophthalmology has been recently proven. The wide use of cytokines inhibitors could also be very useful in the therapy of neovessels in macular degeneration age-related, since the role of inflammation in the proliferation of neovessels has been recently discovered.

Mantel I, Zografos L. · Hôpital Ophtalmique Jules Gonin, Lausanne, University of Lausanne, 15, avenue de France, 1004 Lausanne, Suisse. · J Fr Ophtalmol. · Pubmed #12819609 links to  free full text

Abstract: The presence of a chorioretinal anastomosis in the setting of age-related macular degeneration is known as a sign of poor prognosis. No treatment has proven to be effective. We describe a 71-year-old female patient presenting with exudative age-related macular degeneration, a chorioretinal anastomosis with two retinal feeder vessels (arteriole and veinule), a serous retinal pigment epithelium detachment, and a suspected early subretinal neovascular membrane. She was treated with ICG-guided laser photocoagulation directed to the hot spot, with treatment-zone enlargement directed to the retinal feeder vessels and followed up for 6 months. Although a second laser treatment for the reperfused subretinal neovascular membrane was needed, the clinical and angiographic end result was beneficial. Visual acuity improved by two lines, the chorioretinal anastomosis was occluded, and the pigment epithelium reattached. Taking into account the low therapeutic success rate described in the literature, we suggest that the specific treatment of the retinal feeder vessels, which to our knowledge has not been described before, may be a valuable treatment option.

Schwoerer J, Secrétan M, Zografos L, Piguet B. · University Eye Department, Jules Gonin Hospital, Lausanne, Switzerland. · Ophthalmologica. · Pubmed #10859505 No free full text.

Abstract: PURPOSE: To describe the characteristic findings of fundus flavimaculatus (Stargardt disease) as seen on indocyanine green angiography. METHODS: Twelve eyes of 6 consecutive patients with fundus flavimaculatus were studied by fundus color photographs, fluorescein angiography and indocyanine green angiography. RESULTS: Indocyanine green angiography allowed visualization of small, clearly demarcated areas in which hypofluorescence increased over time, leading eventually to a large reticular pattern with small areas of normal-appearing choroid encircled by a well-defined network of hypofluorescent curvilinear lesions. These hypofluorescent flecks were present in all 12 eyes but corresponded only partially to the yellow flecks visible on biomicroscopy of the fundus. The peripapillary area was well preserved on indocyanine green angiography and the periphery did not show any visible abnormalities. CONCLUSIONS: The hypofluorescent curvilinear areas visualized on indocyanine green angiography form a reticular pattern that is similar to the polygonal shape of the watershed zones between terminal choroidal arterioles, which supply the choriocapillaris. These dark areas may reflect choriocapillaris defects secondary to lysis of lipofuscin-engorged retinal pigment epithelial cells. The typical lesions of fundus flavimaculatus thus seem to be situated in areas of least vascular supply. Their absence in the peripapillary area, which benefits from anastomotic vascular connections, would support this hypothesis.