Photodynamic therapy for polypoidal choroidal vasculopathy.

The first effective therapy for exudative macular degeneration (AMD) was Photodynamic Therapy (PDT). Diagnosis of the disease was to a large extent by fluorescein angiography (FA). Distinguishing between the leaky choroidal neovessels (CNV) associated with exudative AMD, and the polypoidal structures associated with Polypoidal Choroidal Vasculopathy (PCV) is not always easy using FA alone. The switch to Indocyanine Green angiography helped to pinpoint PCV, and thus to study the efficacy of photodynamic therapy of this particular form of retinal disease, which is more frequently encountered among pigmented individuals. The results appear to be quite promising, and in the year following treatment only a small fraction of the patients had to be retreated. Alternatively, treating PCV with repeated intravitreal VEGF blocking agents was not as successful as it was in the treatment of wet AMD. However, combining PDT-induced angio-occlusion of the polypoidal lesions with anti-vascular endothelial growth factor therapy was shown to be quite effective, and the combination of PDT with an anti-angiogenic agent as well as a steroid, in a triple therapy, was recently also shown to be a quite promising option. In the present article we review the data on PDT of PCV, including combination therapies and alternative treatments. We also report on similarities and differences between AMD and PCV.

Reflectance imaging of the human retina at 810 nm does not suffice to optimize the parameters of hydrodynamic rebalancing laser treatment.

The hydrodynamic rebalancing laser (HRL) procedure is an ophthalmic therapy based on the administration of subthreshold infrared (810 nm) laser light to selected areas on the retina to treat various retina diseases. Heterogeneities of tissue response are observed, including undesired retinal damages. Variations of tissue absorbance were hypothesized to cause this uneven response. Irradiation parameters (diameter = 100 µm; power = 1 W; irradiation time: 50 to 200 ms), location and tissue response were studied in 16 patients (20 eyes, 2535 laser spots) to discover any correlation between tissue response and normalized fundus reflectance at 810 nm. The results demonstrate a complex relationship between some pathologies and occurrences of retinal damage, but no clear correlation. One possible reason is that the resolution of reflectance images is insufficient to see "small" (40 µm or less) absorption centers, particularly deep-seated ones. Additionally, tissue parameters other than variations of the fundus optical absorption influence heat diffusion and temperature increases. Monitoring or individualizing the light dose in HRL therapy, or any similar infrared diode laser-based therapy will require more sophisticated technologies, including imaging the retina's reflectance with an improved resolution, as well as refined methods to detect complex correlations between retinal damage and specific pathologies.

Subretinal neovascular membranes complicating uveitis: frequency, treatments, and visual outcome.

PURPOSE: Retrospective evaluation in a uveitic population of subretinal neovascular membranes (SRNMs), their occurrence, visual impact, and outcome in differently treated subgroups of patients. METHODS: Medical records of patients were reviewed and cases with SRNM (n = 12) identified. Intraocular inflammation was classified according to vitreous examination records as high (2+ cells), low (1/2+ to 1+ cells), or inactive (0 cells). Visual outcome was considered to be +VA (same or gain of one or more Snellen lines) or -VA (loss of Snellen lines). In nine cases, treatment consisted of the oral administration of high doses of corticosteroids (CST) for one month, tapered down in favorable situations (+VA or SRNM angiographic regression) or maintained at half the dose in unfavorable situations (-VA or SRNM angiographic progression) while additional laser therapies, including photodynamic therapy (PDT), transpupillary thermotherapy (TTT), or argon laser therapy (CLT)), were performed in some of the cases. The above treatment scheme was not applied in three cases (pre-PDT period; undiagnosed underlying uveitis treated without CST). RESULTS: Twelve out of 648 patients (1.9%) with uveitis developed SRNM. The mean visual impact was 4.5 Snellen lines and mean follow-up time was 19.5 months. Two patients with high intraocular inflammation had a favorable visual outcome with CST alone. Eight patients with low intraocular inflammation had a favorable visual outcome with CST alone in three cases, with additional laser therapy in four cases (PDT in 3 cases and TTT in 1 case), and exclusively with PDT in one case (undiagnosed uveitis). Two patients with no intraocular inflammation had unfavorable visual outcome with CST alone (no PDT/TTT available). CONCLUSION: SRNMs occurred as a rare complication of uveitis. Their visual outcome was relatively favorable. Although high doses of CST seem to be the first step in the management of SRNMs, alternative laser treatments should be considered early, especially in cases of absence or low intraocular inflammation.

Photodynamic therapy with verteporfin in ocular histoplasmosis: uncontrolled, open-label 2-year study.

OBJECTIVE: To evaluate the safety, effect on visual function, and fluorescein angiographic appearance of subfoveal choroidal neovascularization (CNV) through 2 years after photodynamic therapy with verteporfin (Visudyne; Novartis AG, Basel, Switzerland) in patients with ocular histoplasmosis syndrome (OHS). DESIGN: Open-label, 3-center, uncontrolled clinical study. PARTICIPANTS: Ocular histoplasmosis syndrome patients with subfoveal CNV (N = 26) with a greatest linear dimension no larger than 5400 microm with classic or occult CNV extending under the geometric center of the fovea, and best-corrected visual acuity letter score of approximately 20/40 to 20/200. METHODS: The methods were similar to those described in the 1-year results with follow-up examinations every 3 months continuing through the second year. During the second year, additional therapy was recommended if fluorescein angiography showed leakage at a scheduled visit. MAIN OUTCOME MEASUREMENTS: Visual function measurements included the changes from baseline in visual acuity and contrast sensitivity scores. Lesion size and leakage from classic and occult CNV were assessed at month 12 and month 24. Safety assessments also were made. RESULTS: A 24-month examination was completed in 22 of the 26 enrolled participants (85%). At the 24-month examination, median improvement from baseline in visual acuity of the 22 patients evaluated was 6 letters; median contrast sensitivity improved by 3.5 letters. At the 24-month examination, 10 patients (45%) gained 7 or more letters of visual acuity from baseline, whereas 4 patients (18%) lost 8 or more letters, including 2 patients (9%) who lost at least 15 letters. There was absence of fluorescein angiographic leakage from classic CNV in 17 of the 20 evaluable lesions (85%), and leakage from occult CNV was absent in all eyes. No serious ocular adverse events were reported, and no serious systemic event was considered to be associated with treatment. CONCLUSIONS: Median visual acuity improved and fluorescein angiographic leakage decreased after verteporfin therapy in this small, uncontrolled clinical study of patients with subfoveal CNV resulting from OHS. Verteporfin therapy seemed to be relatively safe in these patients. The selected cases feature fluorescein angiographic examples of CNV that are important in determining when to apply verteporfin therapy.

Acute severe visual acuity decrease after photodynamic therapy with verteporfin: case reports from randomized clinical trials-TAP and VIP report no. 3.

PURPOSE: To describe in detail occurrences of acute severe visual acuity decrease after photodynamic therapy (PDT) with verteporfin in the Treatment of Age-related macular degeneration with Photodynamic therapy (TAP) Investigation and the Verteporfin In Photodynamic therapy (VIP) Trial. DESIGN: Observational case series. METHODS: Retrospective review of all cases that developed acute severe visual acuity decrease after treatment. RESULTS: Of 15 acute severe visual acuity decrease events originally identified in 14 eyes of 14 patients, one event in one patient was judged unlikely to have been an acute severe visual acuity decrease event on retrospective review of these events in preparation of this report. Eleven events occurred after the first treatment. At follow-up, 10 improved by at least 1 line in visual acuity from the level noted at the time of the event. Of the nine patients returning for the month 24 examination, visual acuity decreased at least 3 lines from baseline in six, including at least 6 lines in four, and remained within 1 line in three. Associated abnormal morphology included three with a serous macular detachment and abnormal choroidal hypofluorescence, four with macular hemorrhage, three with a greenish subfoveal hemorrhage, and four with no abnormality. Events appeared to be more likely when patients had a visual acuity of 20/50 or better. CONCLUSIONS: Acute severe visual acuity decrease after PDT with verteporfin was an uncommon event; the risk did not outweigh the benefits of therapy previously reported. When considering verteporfin therapy, patients should be warned of the possibility of this serious adverse event.

Verteporfin therapy of subfoveal choroidal neovascularization in pathologic myopia: 2-year results of a randomized clinical trial--VIP report no. 3.

PURPOSE: To report 24-month vision and fluorescein angiographic outcomes from trials evaluating photodynamic therapy with verteporfin in patients with subfoveal choroidal neovascularization (CNV) caused by pathologic myopia. DESIGN AND SETTING: Multicenter, double-masked, placebo-controlled, randomized clinical trial at 28 ophthalmology practices in Europe and North America. PARTICIPANTS: Patients with subfoveal choroidal neovascular lesions caused by pathologic myopia measuring no more than 5400 micro m and best-corrected visual acuity (approximate Snellen equivalent) of 20/100 or better. METHODS: Similar to methods described for 1-year results with follow-up examinations beyond 1 year, continuing every 3 months (except Photograph Reading Center evaluations only at the month 24 examination). During the second year, the same regimen (with verteporfin or placebo as applied at baseline) was used if angiography showed fluorescein leakage from CNV. MAIN OUTCOME MEASURES: The primary outcome was the proportion of eyes with fewer than 8 letters (approximately 1.5 lines) of visual acuity loss at the month 24 examination, adhering to an intent-to-treat analysis and using the last observation carried forward method to impute for any missing data. RESULTS: Seventy-seven of 81 patients (95%) in the verteporfin group, compared with 36 of 39 patients (92%) in the placebo group, completed the month 24 examination. At this time point, 29 of 81 verteporfin-treated patients (36%) compared with 20 of 39 placebo-treated patients (51%) lost at least 8 letters (P = 0.11). The distribution of change in visual acuity at the month 24 examination was in favor of a benefit for the cases assigned to verteporfin (P = 0.05). This included improvement by at least 5 letters (equivalent to at least 1 line) in 32 verteporfin-treated cases [40%] vs. five placebo-treated cases (13%) and improvement by at least 15 letters (equivalent to at least 3 lines) in 10 verteporfin-treated cases (12%) vs. zero placebo-treated cases. No additional photosensitivity adverse reactions or injection site adverse events were associated with verteporfin therapy in the second year of follow-up. CONCLUSIONS: Verteporfin therapy for subfoveal CNV caused by pathologic myopia safely maintained a visual benefit compared with a placebo therapy through 2 years of follow-up. Although the primary outcome was not statistically significantly in favor of verteporfin therapy at 2 years as it had been at 1 year of follow-up, the distribution of change in visual acuity at the month 24 examination was in favor of the verteporfin-treated group and showed that this group was more likely to have improved visual acuity through the month 24 examination. The VIP Study Group recommends verteporfin therapy for subfoveal CNV resulting from pathologic myopia based on both the 1- and 2-year results of this randomized clinical trial.

Photodynamic therapy of subfoveal choroidal neovascularization with verteporfin in the ocular histoplasmosis syndrome: one-year results of an uncontrolled, prospective case series.

OBJECTIVE: To evaluate the safety and effect on visual acuity of photodynamic therapy with verteporfin (Visudyne, Novartis AG) in patients with subfoveal choroidal neovascularization (CNV) secondary to the ocular histoplasmosis syndrome (OHS). DESIGN: Open-label, three-center, noncomparative prospective case series. PARTICIPANTS: OHS patients with subfoveal CNV lesions no larger than 5400 micro m in greatest linear dimension (GLD) with classic or occult CNV extending under the geometric center of the foveal avascular zone and best-corrected visual acuity letter score of 73 to 34 (approximate Snellen equivalent 20/40-20/200). METHODS: Twenty-six patients received verteporfin (6 mg/m(2)) infused IV over 10 minutes. Fifteen minutes after the start of infusion, a laser light at 689 nm delivered 50 J/cm(2) at an intensity of 600 mW/cm(2) over 83 seconds using a spot size with a diameter 1000 micro m larger than the GLD of the lesion. At 3-month follow-up examinations, retreatment with the same regimen was applied if angiography showed fluorescein leakage. Safety assessments were also made. MAIN OUTCOME MEASURES: Visual function measurements were the changes from baseline in visual acuity and contrast sensitivity scores and the proportion of patients who, based on best-corrected visual acuity scores, (1) gained 7 or more letters, (2) lost 8 or more letters, and (3) lost 15 or more letters. RESULTS: One patient was omitted from the study at the month 3 examination for not meeting the visual acuity eligibility requirements at baseline. By the month 12 examination, but excluding any retreatment at that visit, patients had received an average of 2.9 treatments of a maximum of 4 possible treatments. The month 12 median improvement from baseline in visual acuity of the remaining 25 patients was 7 letters, and median contrast sensitivity improved by 2 letters. Median visual acuity improvement was also 7 letters when three patients, who failed to meet all photographic eligibility requirements at baseline, were excluded. At the month 12 examination, 14 (56%) patients gained 7 or more letters of visual acuity from baseline, whereas 4 (16%) patients lost 8 or more letters, of which 2 (8%) lost 15 or more letters. No serious systemic or ocular adverse events were reported. CONCLUSIONS: Median visual acuity improved after verteporfin therapy for at least 1 year in a small uncontrolled prospective case series of patients with subfoveal CNV caused by OHS. Verteporfin therapy seemed to be safe and well tolerated in these patients. Two-year data from this study will provide important, additional information on the safety and effect of verteporfin therapy for the treatment of subfoveal CNV secondary to OHS.