[Solitary albinotic spot of the retinal pigment epithelium: a functional and imaging study]. / Solitärer, albinotischer "Fleck" des retinalen Pigmentepithels: klinische und funktionelle Befunde.

PURPOSE: The presence or absence of functional changes associated with solitary, congenital, hypopigmented lesions of the retinal pigment epithelium (RPE) have been a matter of controversy. This case report describes retinal and functional findings in a young patient with such a lesion. METHODS: A 10-year-old Hispanic female with a solitary congential hypopigmented spot of the RPE was examined using fundus photography, fluorescein angiography, autofluorescence imaging (AF) and optical coherence tomography (OCT). Functional analyses were performed using the Humphrey 24 - 2 visual field, Goldmann perimetry and the multifocal ERG (mfERG). RESULTS: A small visual field defect was demonstrated on both Goldmann perimetry (I/ 2e test object) and on Humphrey 24 - 2 visual field testing (significant at the 0.5 % level for pattern deviation). The multifocal ERG response amplitudes were decreased in the corresponding area and increased in implicit time. Autofluorescence imaging showed an absence of fluorescence corresponding to the area of the lesion. OCT findings were indicative of a small amount of subretinal fluid or schisis-like changes overlying the RPE anomaly. CONCLUSION: The results indicate that solitary, albinotic spots of the RPE can be associated with visual field defects and outer retinal deficits; these may be related to impaired RPE function and/or chronic exudative changes.

A method of drusen measurement based on reconstruction of fundus background reflectance.

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.

[Changes in neovascular membranes and normal choroid blood vessels after multiple photodynamic therapy treatments]. / Veränderungen neovaskulärer Membranen und normaler Aderhautgefässe nach mehrfacher photodynamischer Therapie.

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.

[Spontaneous course of classical, subfoveal choroid neovascularization in age-related macular degeneration]. / Spontanverlauf bei klassischer, subfovealer chorioidaler Neovaskularisation bei AMD.

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.

[Choroidal changes after photodynamic therapy (PDT). A two-year follow-up study of 38 patients]. / Aderhautveränderungen nach photodynamischer Therapie (PDT). Verlaufsbeobachtungen über 2 Jahre bei 38 Patienten.

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.

Evaluation of functional defects in branch retinal vein occlusion before and after laser treatment with scanning laser perimetry.

OBJECTIVE: This study was aimed at localizing and quantifying retinal defects in patients with branch retinal vein occlusion by means of scanning laser perimetry and analyzing the mechanism involved in the functional recovery after laser therapy. DESIGN: Prospective nonrandomized clinical trial with concurrent comparison group. PARTICIPANTS: Fifty-eight patients with isolated branch retinal vein occlusion. Thirty-nine eyes received laser treatment; 19 eyes were observed without treatment. INTERVENTION: Argon laser photocoagulation was performed according to the Branch Vein Occlusion Study recommendations. MAIN OUTCOME MEASURES: Retinal functional deficits were evaluated with scanning laser perimetry and fluorescein angiography first at baseline, at 3-month follow-up visits and 3 months after laser treatment. RESULTS: After laser treatment, the scotoma encroached on foveal fixation in 31% of eyes, remained stable in 36%, and regressed from the foveal avascular zone in 33%. Improvement in vision was correlated with increasing scotoma distance from fixation. Total scotoma size increased in 50% of eyes after treatment. Depth of scotoma and degree of angiographic leakage showed no direct correlation. CONCLUSIONS: Stabilization and increase in visual acuity after laser treatment did not correlate with an overall decrease in scotoma size. Improved central visual function seen in 25% of treated eyes appeared to be due to withdrawal of scotoma from the fovea.

Photodynamic therapy of choroidal hemangioma: two case reports.

BACKGROUND: Photocoagulation, cryotherapy and radiotherapy have been used to treat angiomatous lesions. Depending on the location of the angioma, these treatments can cause additional, significant functional damage. Photodynamic therapy (PDT) however, allows a selective occlusion of vascular lesions without damaging adjacent retinal structures. METHODS: Two patients with isolated choroidal hemangiomas involving the posterior pole were treated with PDT. Treatments were performed using a diode laser at 692 nm, a light dose of 100 J/cm2 and 6 mg/m2 body surface area verteporfin (BPD-MA). PDT was applied in two courses in one eye and in four in the other eye at 1-4 months intervals. Patients were followed up for 9-12 months with visual acuity measurements and dilated ophthalmoscopy. Ultrasound, indocyanine green angiographic and fluorescein angiographic images were evaluated at each visit. RESULTS: Tumor heights were 3.3 and 4.6 mm on pretreatment ultrasound. After therapy, patients with isolated choroidal hemangioma showed total regression of the lesion and improved visual acuity due to resorption of retinal edema. Serous retinal detachment and cystoid macular edema resolved. Ultrasound demonstrated a progressive decrease in tumor height after each PDT application, with complete disappearance of the lesion. Retinal vessels were not affected by the treatment, and retinal function recovered in areas with previous tumor involvement. CONCLUSION: PDT allows selective treatment of large intraocular angiomatous lesions. Without optimized parameters, complete regression of choroidal hemangiomas, resolution of secondary complications and improvement of visual acuity were documented.

A preliminary study of photodynamic therapy using verteporfin for choroidal neovascularization in pathologic myopia, ocular histoplasmosis syndrome, angioid streaks, and idiopathic causes.

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.

Photodynamic therapy with verteporfin for choroidal neovascularization caused by age-related macular degeneration: results of a single treatment in a phase 1 and 2 study.

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.

Photodynamic therapy with verteporfin for choroidal neovascularization caused by age-related macular degeneration: results of retreatments in a phase 1 and 2 study.

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.

[Photodynamic therapy: ICG angiography findings]. / Photodynamische Therapie: ICG-angiographische Befunde.

PURPOSE: Photodynamic therapy (PDT) has been shown to provide immediate occlusion of choroidal neovascularization (CNV), followed by recurrent leakage after single PDT in the majority of the cases after 3 months. Indocyanine green angiography (ICG-A) was used to evaluate completeness of CNV occlusion, effects on physiological choroid and patterns of CNV recurrence. METHODS: ICG-A was performed using a confocal laser scanning ophthalmoscope (HRA) before PDT at 1 week, 4 and 12 weeks following PDT. Twenty patients with single and 10 patients with repeated PDT treatments with administration of benzoporphyrin derivative and radiant exposures between 50 and 150 J/cm2 were evaluated. RESULTS: Before PDT well-defined CNV was detectable during early ICG-A in all lesions. Depending on the number of treatments, CNV was absent in early phase ICG-A in 46-83%. CNV reappeared at week 4 in many and at 12 weeks in 77 (66%) of the cases. The treated area regularly showed hypofluorescence, which persisted until week 12. The intensity of choroidal hypofluorescence showed wide interindividual variability. Recurrence may originate from persistent feeder vessels. CONCLUSION: With ICG-A we demonstrated that PDT induces hypofluorescence of CNV and choroid possibly due to perfusion changes or blockade phenomena. Recurrence may be due to reperfusion of the preexisting CNV or regrowth from feeder vessels.

[Quantification of functional retinal damage in branch retinal vein thromboses]. / Quantifizierung der funktionellen Netzhautschädigung bei Venenastthrombosen.

PURPOSE: Branch retinal vein occlusion (BRVO) induces variable functional deficits depending on the grade of vascular occlusion and its localisation. Theses deficiences are not easily defined by visual acuity measurements. However, microperimetry offers topical mapping of retinal function, allowing precise documentation of the intensity and dimension of retinal functional loss in BRVO. METHODS: Retinal sensitivity was examined using a Rodenstock Scanning Laser Ophthalmoscope (SLO). A standardized grading system of stimuli ranging from 0 to 32 dB was used to document the retinal threshold in three different areas: regions presenting vascular occlusion, the collateral edematous zone and adjacent areas with intact perfusion. Absolute and relative scotomas as well as the fixation behavior were studied. RESULTS: Forty-two patients with isolated BRVO within the vascular arcades were examined with microperimetry and angiography. At initial presentation with BRVO the retinal sensitivity in the area of occlusion on average diminished to 4.1 dB. In the collateral edematous zone retinal threshold was reduced to 21.5 dB; area with intact perfusion demonstrated a threshold of 23.2 dB. Within the occluded area itself defects of significantly differing intensity were found which only partially correlated with the angiographic evidence. Intense scotomas (0 dB) were observed in 59% of the eyes examined: angiographically nonperfused areas or extended intraretinal hemorrhage were present. Relative scotomas (12.1 dB) were seen in 19.1% and minimal, non-significant defects (19.5 dB) were documented in 21.4% of the BRVO. The level of angiographically documented leakage did not correlate with the functional deficits present in these two groups. Measurements performed after 6-8 weeks revealed noticeable spontaneous recovery of retinal sensitivity, unless an additional progressive closure occurred. The average functional improvement in the area of leakage found after laser therapy was less than the results shown in spontaneous resolution of edema. CONCLUSIONS: BRVO may lead to significant reductions of central and paracentral retinal function. Angiographically observed leakage is not always directly correlated to the magnitude of retinal sensitivity loss. As spontenous remission is frequent in one group and intact retinal function can be shown in areas of angiographic leakage, therapeutic interventions, e.g., laser treatment, should be carefully considered. Scanning laser ophthalmoscopy provides additional information for precise evaluation and follow-up of the retinal damage in BRVO.