Faculty Bibliography

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.

OBJECTIVE: To evaluate the potential benefit and risks of photodynamic therapy (PDT) in the treatment of papillary capillary hemangioma. DESIGN: Prospective, noncomparative, interventional case series. PARTICIPANTS: Five patients with solitary capillary hemangioma on the temporal portion of the optic nerve presenting with exudative decompensation and decrease in visual acuity (VA). METHODS: All eyes received a standardized PDT treatment with 6 mg/kg body surface area verteporfin and application of 100 J/cm(2) light at 692 nm. One to three PDT courses were performed until resolution of exudation was achieved. A continuous follow-up was provided with documentation 1 week before and at 4 to 6 weeks, 3 months, and 12 months after the last treatment application. MAIN OUTCOME MEASURES: Functional parameters included best-refracted VA (Early Treatment Diabetic Retinopathy Study), and central scanning laser ophthalmoscope (SLO) scotometry and peripheral (automated perimetry) visual fields; anatomic parameters were presence of retinal edema or serous detachment (ophthalmoscopy) and tumor size (ultrasonography). RESULTS: Pretreatment VA levels ranged from 20/40 to 20/800; posttreatment levels ranged from 20/64 to 20/2000. Tumor regression with resolution of macular exudate and serous retinal detachment was obtained in all eyes. A decline in VA of 1, 3, and 10 lines, respectively, was documented in three patients. Complications included transient decompensation of vascular permeability, occlusion of retinal vessels, and ischemia of the optic nerve. CONCLUSIONS: PDT is successful in reducing tumor size and exudative activity. Vaso-occlusive effects at the level of the retina and optic nerve compromise the functional benefit. Parameters proven safe in choroidal neovascularization may be inappropriate in retinal capillary lesions of the optic nerve.

PURPOSE: To measure the oxygen tension (PO2) in the rabbit vitreous and lens and to investigate the mechanism by which it is controlled, the affection on oxygen tension of the lens after vitrectomy was studied. METHODS: Using a fiber-optic oxygen sensor system, oxygen tension of the rabbit vitreous and lens was probed in vivo and oxygen permeability of posterior capsule was also measured on isolated rabbit lens. RESULTS: It was found that with agreement with previous study, PO2 is relatively high and the PO2 gradient is large in vitreous body close to the retina whereas more than 0.5 mm away from the retina the vitreal PO2 is relatively low and the PO2 gradient is very shallow. Oxygen tension in the lens is asymmetric with the anterior being higher than the posterior and oxygen in the posterior lens being at the similar tension as the anterior vitreous behind the lens. The posterior capsule of the rabbit lens is relatively high in oxygen permeability. CONCLUSIONS: The vitreous body plays a key role in maintaining a low and stable level of oxygen in the lens. After vitrectomy oxygen tension in the lens may increase.

PURPOSE: To evaluate the effect of photodynamic therapy (PDT) on perfusion and vascular integrity of choroidal neovascularization (CNV) and collateral physiological choroid. METHODS: In a prospective clinical trial, patients with subfoveal CNV were treated with PDT and verteporfin. Indocyanine green angiography (ICG-A), using a confocal laser scanning system with tomographic sections, was performed continuously 1 week before and 1, 4, and 12 weeks after and a mean long-term follow-up of 16.5 months after the final PDT. Vascular changes were localized tomographically and quantified on the level of the CNV and collateral choroid according to early lesion size, late hyperfluorescence, and persistence or recurrence. Data were analyzed separately from 38 eyes in a single- and 12 eyes in a multiple-treatment regimen. RESULTS: CNV lesions were significantly reduced in size and late hyperfluorescence. However, 54% of lesions primarily demonstrated persistence, typically of the choroidal feeding complex, which was only detectable by ICG-A. Regrowth from the feeding vessel occurred regularly, but did not reach baseline dimensions. Collateral choroid exposed to photoactivation exhibited choriocapillary occlusion. Progressive recanalization was documented within 4 to 12 weeks after both single and multiple PDT. Residual changes in the choroidal filling pattern often persisted during long-term follow-up. CONCLUSIONS: Tomographic ICG-A after PDT reveals persistence of CNV and/or the feeder vessel and a reduction in perfusion within the entire photosensitized area, including the surrounding choroid. Repair mechanisms occur slowly in neovascular and normal choroidal structures.

PURPOSE: To determine if photodynamic therapy with verteporfin (Visudyne; Novartis AG, Bülach, Switzerland), termed verteporfin therapy, can safely reduce the risk of vision loss compared with a placebo (with sham treatment) in patients with subfoveal choroidal neovascularization caused by age-related macular degeneration who were identified with a lesion composed of occult with no classic choroidal neovascularization, or with presumed early onset classic choroidal neovascularization with good visual acuity letter score. METHODS: This was a double-masked, placebo-controlled (sham treatment), randomized, multicenter clinical trial involving 28 ophthalmology practices in Europe and North America. The study population was patients with age-related macular degeneration, with subfoveal choroidal neovascularization lesions measuring no greater than 5400 microm in greatest linear dimension with either 1) occult with no classic choroidal neovascularization, best-corrected visual acuity score of at least 50 (Snellen equivalent approximately 20/100), and evidence of hemorrhage or recent disease progression; or 2) evidence of classic choroidal neovascularization with a best-corrected visual acuity score of at least 70 (better than a Snellen equivalent of approximately 20/40); assigned randomly (2:1) to verteporfin therapy or placebo therapy. Verteporfin (6 mg per square meter of body surface area) or placebo (5% dextrose in water) was administered by means of intravenous infusion of 30 ml over 10 minutes. Fifteen minutes after the start of the infusion, a laser light at 689 nm delivered 50 J/cm(2) by application of an intensity of 600 mW/cm(2) over 83 seconds using a spot size with a diameter 1000 microm larger than the greatest linear dimension of the choroidal neovascularization lesion on the retina. At follow-up examinations every 3 months, retreatment with the same regimen was applied if angiography showed fluorescein leakage. The main outcome measure was at least moderate vision loss, that is, a loss of at least 15 letters (approximately 3 lines), adhering to an intent-to-treat analysis with the last observation carried forward to impute for missing data. RESULTS: Two hundred ten (93%) and 193 (86%) of the 225 patients in the verteporfin group compared with 104 (91%) and 99 (87%) of the 114 patients in the placebo group completed the month 12 and 24 examinations, respectively. On average, verteporfin-treated patients received five treatments over the 24 months of follow-up. The primary outcome was similar for the verteporfin-treated and the placebo-treated eyes through the month 12 examination, although a number of secondary visual and angiographic outcomes significantly favored the verteporfin-treated group. Between the month 12 and 24 examinations, the treatment benefit grew so that by the month 24 examination, the verteporfin-treated eyes were less likely to have moderate or severe vision loss. Of the 225 verteporfin-treated patients, 121 (54%) compared with 76 (67%) of 114 placebo-treated patients lost at least 15 letters (P =.023). Likewise, 67 of the verteporfin-treated patients (30%) compared with 54 of the placebo-treated patients (47%) lost at least 30 letters (P =.001). Statistically significant results favoring verteporfin therapy at the month 24 examination were consistent between the total population and the subgroup of patients with a baseline lesion composition identified as occult choroidal neovascularization with no classic choroidal neovascularization. This subgroup included 166 of the 225 verteporfin-treated patients (74%) and 92 of the 114 placebo-treated patients (81%). In these patients, 91 of the verteporfin-treated group (55%) compared with 63 of the placebo-treated group (68%) lost at least 15 letters (P =.032), whereas 48 of the verteporfin-treated group (29%) and 43 of the placebo-treated group (47%) lost at least 30 letters (P =.004). Other secondary outcomes, including visual acuity letter score worse than 34 (approximate Snellen equivalent of 20/200 or worse), mean change in visual acuity letter score, development of classic choroidal neovascularization, progression of classic choroidal neovascularization and size of lesion, favored the verteporfin-treated group at both the month 12 and month 24 examination for both the entire study group and the subgroup of cases with occult with no classic choroidal neovascularization at baseline. Subgroup analyses of lesions composed of occult with no classic choroidal neovascularization at baseline suggested that the treatment benefit was greater for patients with either smaller lesions (4 disc areas or less) or lower levels of visual acuity (letter score less than 65, an approximate Snellen equivalent of 20/50(-1) or worse) at baseline. Prospectively planned multivariable analyses confirmed that these two baseline variables affected the magnitude of treatment benefit. (ABSTRACT TRUNCATED

Objective: To determine if photodynamic therapy with verteporfin (Visudyne; CIBA Vision Corp, Duluth, GA) can improve the chance of stabilizing or improving vision (<8 letter loss) safely in patients with subfoveal choroidal neovascularization (CNV) caused by pathologic myopia. Design: Multicenter, double-masked, placebo-controlled, randomized clinical trial at 28 ophthalmology practices in Europe and North America. Participants: One hundred twenty patients with subfoveal CNV caused by pathologic myopia with a greatest linear dimension no more than 5400 <mu>m and best-corrected visual acuity (Snellen equivalent) of approximately 20/100 or better. Intervention: Patients were randomly assigned (2:1) to verteporfin (6 mg per square meter of body surface area; n = 81) or placebo (5% dextrose in water, n = 39) administered via intravenous infusion of 30 ml over 10 minutes. Fifteen minutes after the start of the infusion, a laser light at 689 nm was delivered at an intensity of 600 mW/cm(2) over 83 seconds to give a light dose of 50 J/cm(2) to a round spot size on the retina with a diameter of 1000 mum larger than the greatest linear dimension of the choroidal neovascular lesion. At follow-up examinations every 3 months, retreatment with either verteporfin or placebo (as assigned at baseline) was applied to areas of fluorescein leakage if present. Main Outcome Measures: The primary outcome was the proportion of eyes at the follow-up examination 12 months after study entry with fewer than eight letters (approximately 1.5 lines) of visual acuity lost, adhering to an intent-to-treat analysis. Results: At baseline, move than 90% of each group had evidence of classic CNV (regardless of whether occult CNV was present) and only 12 (15%) and 5 (13%) cases in the verteporfin and placebo groups, respectively, had occult CNV (regardless of whether classic CNV was present). Seventy-nine of the 81 verteporfin-treated patients (98%) compared with 36 of the 39 placebo-treated patients (92%) completed the month 12 examination. Visual acuity, contrast sensitivity, and fluorescein angiographic outcomes were better in the verteporfin-treated eyes than in the placebo-treated eyes at every follow-up examination through the month 12 examination. At the month 12 examination, 58 (72%) of the verteporfin-treated patients compared with 17 (44%) of the placebo-treated patients lost fewer than eight letters (P < 0.01), including 26 (32%) versus 6 (15%) improving at least five letters (<greater than or equal to>1 line). Seventy (86%) of the verteporfin-treated patients compared with 26 (67%) of the placebo-treated patients lost fewer than 15 letters (P = 0.01), Few ocular or other systemic adverse events were associated with verteporfin therapy compared with placebo treatment. Conclusions: Because photodynamic therapy with verteporfin can safely increase the chance of stabilizing or improving vision in patients with subfoveal CNV from pathologic myopia compared with a placebo, we recommend ophthalmologists consider verteporfin therapy for treatment of such patients. Ophthalmology 2001; 108:841-852 (C) 2001 by the American Academy of Ophthalmology. $$:

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.

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.