Macular Degeneration: Barbazetto I

Mennel S, Barbazetto I, Meyer CH, Peter S, Stur M. · Department of Ophthalmology, Philipps University, Marburg, Germany. · Ophthalmologica. · Pubmed #17728549 No free full text.

Abstract: Photodynamic therapy (PDT) has become a well-established treatment for vascular forms of age-related macular degeneration (AMD). The implementation of evidence-based medicine principles into the treatment regimen of AMD seems to be immensly important, since AMD continues to be the most frequent cause of blindness among patients older than 65 years in industrialized countries. Numerous randomized prospective studies demonstrated high levels of evidence for the efficacy of various treatment approaches such as laser photocoagulation, PDT, subretinal surgery or novel anti-angiogenic drugs [Arch Ophthalmol 2006;124:597-599]. The high evidence shown by these studies supported the rationale to use PDT also in additional, less frequent, vasoproliferative diseases. Although these 'case series' and 'individual case control studies' have a low level of evidence, they give us important information for treatment decisions in these rare conditions. The goal of this survey is to review the current literature regarding PDT in vasoproliferative and exudative ocular diseases outside AMD. Many studies modified the treatment parameters of PDT to address the specific pathology of the underlying disease. Table 1 summarizes the diseases and treatment parameters that are described in this part 2, the entire table of this review is included in part 1 (www.karger.com/doi/10.1159/ 000101922).

Mennel S, Barbazetto I, Meyer CH, Peter S, Stur M. · Department of Ophthalmology, Philipps University Marburg, Robert-Koch-Strasse 4, DE-35037 Marburg, Germany. · Ophthalmologica. · Pubmed #17579286 No free full text.

Abstract: Ocular photodynamic therapy (PDT) was introduced as a novel treatment for neovascular forms of age-related macular degeneration and choroidal neovascularization (CNV) secondary to pathologic myopia in the mid/end 1990s. The current treatment recommendations are based on the results of two large, prospective, multicenter, randomized clinical trials (Treatment of Age-Related Macular Degeneration with Photodynamic Therapy and Verteporfin in Photodynamic Therapy Studies) and thousands of patients have been treated worldwide over the last years. Meanwhile, PDT has been performed in several other ocular pathologies with some remarkable results, however, with most reports being case reports and small case series without statistical significance. These extended applications include CNV secondary to choroiditis and retinochoroiditis, angioid streaks, central serous chorioretinopathy, retinal angiomatous proliferation, parafoveal telangiectasia or CNV associated with macular dystrophy and idiopathic CNV, as well as diseases without CNV, such as choroidal hemangioma, retinal hamartoma, choroidal melanoma, chronic central serous chorioretinopathy, angiomatous lesions secondary to systemic diseases, rubeosis iridis or neovascular glaucoma. To date, with the introduction of anti-VEGF therapy, the role of PDT will certainly change. However, it is reasonable to believe that it will maintain an important role in combination therapy due to its unique properties of selective vascular targeting. Therefore, it is essential for the ophthalmologist to be familiar with the extended applications and their modifications of treatment parameters. This review will summarize the standard and experimental applications of PDT based on our own results and the literature.

Ergun E, Maár N, Radner W, Barbazetto I, Schmidt-Erfurth U, Stur M. · Department of Ophthalmology, University of Vienna Medical School, Vienna, Austria. · Ophthalmology. · Pubmed #12511348 No free full text.

Abstract: PURPOSE: To investigate the correlation between reading speed and scotoma size in patients with subfoveal occult with no classic choroidal neovascularization (CNV) in age-related macular degeneration (AMD) participating at 2 of 28 centers in the Verteporfin in Photodynamic Therapy trial. DESIGN: Prospective, observational case series. PARTICIPANTS: Twenty-two eyes of 22 patients with occult with no classic CNV in AMD. METHODS: Patients' reading speed was examined using a German-language reading test (Radner Lesetest). Scotoma size was measured using the microperimetry program 2.01 of the Rodenstock Scanning Laser Ophthalmoscope. MAIN OUTCOME MEASURES: Reading acuity, reading speed, size of absolute (AS) and relative scotoma (RS). RESULTS: There was a significant correlation between the size of AS and reading speed (r = -0.48, P = 0.023), as well as AS and reading acuity (r = 0.52, P = 0.013). No correlation was seen between RS and reading speed or reading capacity. CONCLUSION: The size of absolute scotoma correlated significantly with reading capacity and reading speed and may influence these measures.

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.

Hageman GS, Anderson DH, Johnson LV, Hancox LS, Taiber AJ, Hardisty LI, Hageman JL, Stockman HA, Borchardt JD, Gehrs KM, Smith RJ, Silvestri G, Russell SR, Klaver CC, Barbazetto I, Chang S, Yannuzzi LA, Barile GR, Merriam JC, Smith RT, Olsh AK, Bergeron J, Zernant J, Merriam JE, Gold B, Dean M, Allikmets R. · Department of Ophthalmology and Visual Sciences, Cell Biology and Functional Genomics Laboratory, University of Iowa, Iowa City, IA 52240, USA. · Proc Natl Acad Sci U S A. · Pubmed #15870199 links to  free full text

Abstract: Age-related macular degeneration (AMD) is the most frequent cause of irreversible blindness in the elderly in developed countries. Our previous studies implicated activation of complement in the formation of drusen, the hallmark lesion of AMD. Here, we show that factor H (HF1), the major inhibitor of the alternative complement pathway, accumulates within drusen and is synthesized by the retinal pigmented epithelium. Because previous linkage analyses identified chromosome 1q25-32, which harbors the factor H gene (HF1/CFH), as an AMD susceptibility locus, we analyzed HF1 for genetic variation in two independent cohorts comprised of approximately 900 AMD cases and 400 matched controls. We found association of eight common HF1 SNPs with AMD; two common missense variants exhibit highly significant associations (I62V, chi2 = 26.1 and P = 3.2 x 10(-7) and Y402H, chi2 = 54.4 and P = 1.6 x 10(-13)). Haplotype analysis reveals that multiple HF1 variants confer elevated or reduced risk of AMD. One common at-risk haplotype is present at a frequency of 50% in AMD cases and 29% in controls [odds ratio (OR) = 2.46, 95% confidence interval (1.95-3.11)]. Homozygotes for this haplotype account for 24% of cases and 8% of controls [OR = 3.51, 95% confidence interval (2.13-5.78)]. Several protective haplotypes are also identified (OR = 0.44-0.55), further implicating HF1 function in the pathogenetic mechanisms underlying AMD. We propose that genetic variation in a regulator of the alternative complement pathway, when combined with a triggering event, such as infection, underlie a major proportion of AMD in the human population.

Smith RT, Chan JK, Nagasaki T, Ahmad UF, Barbazetto I, Sparrow J, Figueroa M, Merriam J. · Edward S. Harkness Eye Institute, New York Presbyterian Medical Center, New York, NY 10032, USA. · Arch Ophthalmol. · Pubmed #15710816 No free full text.

Abstract: BACKGROUND: Age-related macular degeneration (ARMD) is the most prevalent cause of visual loss in patients older than 60 years in the United States. Observation of drusen is the hallmark finding in the clinical evaluation of ARMD. OBJECTIVES: To segment and quantify drusen found in patients with ARMD using image analysis and to compare the efficacy of image analysis segmentation with that of stereoscopic manual grading of drusen. DESIGN: Retrospective study. SETTING: University referral center.Patients Photographs were randomly selected from an available database of patients with known ARMD in the ongoing Columbia University Macular Genetics Study. All patients were white and older than 60 years. INTERVENTIONS: Twenty images from 17 patients were selected as representative of common manifestations of drusen. Image preprocessing included automated color balancing and, where necessary, manual segmentation of confounding lesions such as geographic atrophy (3 images). The operator then chose among 3 automated processing options suggested by predominant drusen type. Automated processing consisted of elimination of background variability by a mathematical model and subsequent histogram-based threshold selection. A retinal specialist using a graphic tablet while viewing stereo pairs constructed digital drusen drawings for each image. MAIN OUTCOME MEASURES: The sensitivity and specificity of drusen segmentation using the automated method with respect to manual stereoscopic drusen drawings were calculated on a rigorous pixel-by-pixel basis. RESULTS: The median sensitivity and specificity of automated segmentation were 70% and 81%, respectively. After preprocessing and option choice, reproducibility of automated drusen segmentation was necessarily 100%. CONCLUSIONS: Automated drusen segmentation can be reliably performed on digital fundus photographs and result in successful quantification of drusen in a more precise manner than is traditionally possible with manual stereoscopic grading of drusen. With only minor preprocessing requirements, this automated detection technique may dramatically improve our ability to monitor drusen in ARMD.

Smith RT, Chan JK, Nagasaki T, Sparrow JR, Barbazetto I. · Harkness Eye Institute, Columbia University College of Pysicians and Surgeons, New York, NY 10032, USA. · Br J Ophthalmol. · Pubmed #15615753 links to  free full text

Abstract: BACKGROUND: The hallmarks of age related macular degeneration (AMD) are the subretinal deposits known as drusen. Current manual methods of drusen segmentation and quantification are laborious and subjective. The authors introduced a digital method and tested it for accuracy and reliability. METHODS: Fourteen eyes with drusen were selected. The authors digitally reconstructed the macular background using normal background areas ("dots") fitted to quadratic polynomials in two zones. The model was used to level the reflectance for the purpose of segmenting drusen by a global threshold. Measurements of drusen areas were compared with those of a semi-automated background levelling technique and manual drawings from stereo pairs. RESULTS: Intraobserver reproducibility had standard deviations from 0.1% to 4.1%. Interobserver reproducibility yielded 95% limits of agreement of -2.7% to 6.3%. The dots method compared with manual drawings and with the semi-automated method had 95% limits of agreement of -8.3% to 2.8% and -7.1% to 4.8%, respectively. CONCLUSIONS: The dots method was reproducible and accurate with respect to validated methods. It provided less total operating time and greater precision than that of standard fundus photo grading. With implementation of commercial software, this technique for macular image analysis has potential for use in clinical research.

Barbazetto I, Burdan A, Bressler NM, Bressler SB, Haynes L, Kapetanios AD, Lukas J, Olsen K, Potter M, Reaves A, Rosenfeld P, Schachat AP, Strong HA, Wenkstern A, Anonymous00097, Anonymous00098. · Medizinische Universität zu Lübeck, Klinik für Augenheilkunde, Lübeck, Germany. · Arch Ophthalmol. · Pubmed #12963608 No free full text.

Abstract: OBJECTIVE: To describe fluorescein angiographic guidelines for the use of verteporfin therapy in patients with subfoveal choroidal neovascularization (CNV) secondary to age-related macular degeneration (AMD) or other conditions based on 2-year vision outcomes from the Treatment of Age-Related Macular Degeneration With Photodynamic Therapy (TAP) Investigation and Verteporfin in Photodynamic Therapy (VIP) Trial. METHODS: Three multicenter, double-masked, placebo-controlled randomized clinical trials at 28 ophthalmology clinical centers in Europe and North America involving prospectively identified patients with best-corrected visual acuity (Snellen equivalent) of approximately 20/20 to 20/200, subfoveal CNV secondary to AMD or pathologic myopia with evidence of CNV, and a lesion greatest linear dimension of 5400 micro m or less. Fluorescein angiography was to be performed on all patients at enrollment and at regular 3-month follow-up visits through 2 years. The initial treatment laser spot size and all subsequent treatment decisions were based on the investigator's interpretation of these fluorescein angiograms. Photographic materials forwarded to the Wilmer Photograph Reading Center were reviewed by masked graders. MAIN OUTCOME MEASURES: Baseline angiographic features, including lesion composition and size, morphologic response to treatment during follow-up (eg, absence of leakage), and reliability (kappa values) of grading selected characteristics based on a 10% regrading of baseline visits. RESULTS: Terms and examples of different lesions and lesion components are provided to assist recognition of fluorescein angiographic characteristics of choroidal neovascular lesions that were important in determining when and where to apply verteporfin therapy. The kappa statistics for agreement of identification of lesion characteristics by the Wilmer Photograph Reading Center for these trials ranged from 0.70 to 0.85. CONCLUSIONS: Ophthalmologists should consider interpreting fluorescein angiographic images of subfoveal lesions with terms provided to follow recommendations regarding which patients are most likely to benefit from verteporfin therapy based on results from the TAP Investigation and VIP Trial.

Smith RT, Nagasaki T, Sparrow JR, Barbazetto I, Klaver CC, Chan JK. · Department of Ophthalmology, Columbia University, New York, NY, USA. · Biomed Eng Online. · Pubmed #12740042 links to  free full text

Abstract: BACKGROUND: The hallmarks of age-related macular degeneration, the leading cause of blindness in the developed world, are the subretinal deposits known as drusen. Drusen identification and measurement play a key role in clinical studies of this disease. Current manual methods of drusen measurement are laborious and subjective. Our purpose was to expedite clinical research with an accurate, reliable digital method. METHODS: An interactive semi-automated procedure was developed to level the macular background reflectance for the purpose of morphometric analysis of drusen. 12 color fundus photographs of patients with age-related macular degeneration and drusen were analyzed. After digitizing the photographs, the underlying background pattern in the green channel was leveled by an algorithm based on the elliptically concentric geometry of the reflectance in the normal macula: the gray scale values of all structures within defined elliptical boundaries were raised sequentially until a uniform background was obtained. Segmentation of drusen and area measurements in the central and middle subfields (1000 microm and 3000 microm diameters) were performed by uniform thresholds. Two observers using this interactive semi-automated software measured each image digitally. The mean digital measurements were compared to independent stereo fundus gradings by two expert graders (stereo Grader 1 estimated the drusen percentage in each of the 24 regions as falling into one of four standard broad ranges; stereo Grader 2 estimated drusen percentages in 1% to 5% intervals). RESULTS: The mean digital area measurements had a median standard deviation of 1.9%. The mean digital area measurements agreed with stereo Grader 1 in 22/24 cases. The 95% limits of agreement between the mean digital area measurements and the more precise stereo gradings of Grader 2 were -6.4 % to +6.8 % in the central subfield and -6.0 % to +4.5 % in the middle subfield. The mean absolute differences between the digital and stereo gradings 2 were 2.8 +/- 3.4% in the central subfield and 2.2 +/- 2.7% in the middle subfield. CONCLUSIONS: Semi-automated, supervised drusen measurements may be done reproducibly and accurately with adaptations of commercial software. This technique for macular image analysis has potential for use in clinical research.

Michels S, Barbazetto I, Schmidt-Erfurth U. · Universitätsaugenklinik Lübeck, Ratzeburger Allee 160, 23538 Lübeck. · Ophthalmologe. · Pubmed #11871080 No free full text.

Abstract: PURPOSE: ICG angiography (ICGA) was used to document the effect of repeated PDT (verteporfin) on size and leakage of choroidal neovascularisation in age-related macular degeneration (AMD) and treatment-related side effects on the choroid. METHODS: Forty-two patients were followed over 24 months in a clinical trial for PDT in AMD. The ICGAs were performed every 3 months with a confocal laser scanning system. Patients received repeated verteporfin treatment. At each control visit, the patients were retreated if leakage was present in fluorescein angiography (FA). RESULTS: A continuous, highly significant reduction in CNV size and leakage area was found over 24 months. The initial CNV size dropped by 23% from 3.86 mm2 to 2.98 mm2. The leakage area in the late phase of the angiogram decreased by 30.3% from 5.0 mm2 to 3.5 mm2. A significant side effect of PDT on the choroid was documented by an increased hypofluorescent area in ICGA. The maximum size of the hypofluorescent area was reached after 12 months. At month 24, the choroidal fluorescence showed recovery in respect to area and intensity of fluorescence. But hypofluorescence surrounding the CNV lesion was already present in 40 out of 42 eyes before treatment. CONCLUSION: The ICGA confirms that repeated PDT treatments lead to a significant reduction in CNV size and leakage area over as long as 2 years. CNV lesions are surrounded by choriocapillary hypofluorescence in ICGA. PDT causes further hypoperfusion of the choroid but in the long-term significant recovery of choroidal perfusion was shown.

Elsner H, Barbazetto I, Schmidt-Erfurth U. · Klinik für Augenheilkunde, Medizinische Universität zu Lübeck, Ratzeburgerallee 160, 23538 Lübeck. · Ophthalmologe. · Pubmed #11490746 No free full text.

Abstract: In a prospective, double-blind study, 19 patients with a classical subfoveal choroidal neovascularisation due to AMD were followed-up over a period of 2 years. Every 3 months a standardised visual acuity test, a contrast sensitivity test and fluorescein-angiography were performed. Overall, visual acuity dropped from 20/125 initially down to 20/250 after 2 years. Contrast sensitivity decreased from 23 down to 19 recognised letters. The functionally superior group 1 (n = 7) with a visual acuity of 20/65 at baseline, improved up to 20/50 after 2 years, while group 2 (n = 12) with a baseline visual acuity of 20/125 showed a decrease down to 20/400 after 24 months. Contrast sensitivity stabilised or improved in 10 patients from 22 to 25 letters, while in 9 patients the score dropped from 23 down to 8 recognised letters. The results underline the unfavourable functional prognosis of classical subfoveal lesions in AMD. However, stabilisation is possible depending on baseline visual acuity which is critical whenever results of nonplacebo-controlled studies have to be assessed. Moreover these results suggest that the urgency of a therapeutical intervention might be overestimated. As treatment, a fairly gentle, primarily atraumatic, CNV-selective strategy should be chosen, so that the self-limiting potential of this disease can be utilised in addition to the therapeutic effect.

Michels S, Barbazetto I, Schmidt-Erfurth U. · Klinik für Augenheilkunde, Medizinische Universität zu Lübeck. · Klin Monatsbl Augenheilkd. · Pubmed #11022663 No free full text.

Abstract: BACKGROUND: Photodynamic therapy is a new option for treatment of choroidal neovascularisation in patients with age-related macular degeneration. But choroidal changes and associated angiographic characteristics have not been further evaluated. PATIENTS: Indocyanine green angiography was used to follow 38 patients with subfoveal choroidal neovascularisation in age-related macular degeneration over up to two years. All patients were treated with the photosensitizer Benzoporphyrin Derivative-MA receiving either a single or triple treatment. RESULTS: Indocyanine green angiography shows two effects of photodynamic therapy. On the one hand a selective and lasting closure of choroidal neovascularisation was documented. Choroidal neovascularisation-size and leakage was significantly reduced in the entire treatment group to 20.7% and 28.3% one week after treatment, followed by a slow increase to 33.3% and 41.2% at up to two years longterm follow up. On the other hand photodynamic therapy causes typically a peri-lesional hypofluorescence in Indocyanine green angiography. This hypofluorescence is most likely due to choroidal hypoperfusion and vascular endothelial changes. A continuous increase in fluorescence was shown, reaching again 90% of the pretreatment intensity at 3 months, documenting a good recovery of the choroidal network. CONCLUSION: The results show that photodynamic therapy is an alternative treatment in age-related macular degeneration with choroidal, subfoveal neovascularisation. Indocyaningreen angiography reflects well choroidal changes associated with this therapy and may be helpful to choose treatment intervals.